BACKGROUND OF THE INVENTION In a communication system, it is necessary to artificially add redundant codes to the data stream according to certain rules before information is sent so that a receiving terminal can detect and correct error codes.","RS error correction code is currently one of the most effective and widely used error control encoding measures.","RS codes can be used to correct random errors, and are also suitable for correcting burst errors, and have been widely used in areas such as satellite communications, digital television transmission or the like.","(c, k, 2t) are typically used to represent RS codes; where c is the total length of information data and redundant code, k is the length of the information data, 2t is the length of the redundant code, and t is the maximum number of errors that can be corrected, where c=K+2t.","The number of elements in the Galois field (GF) in the conventional RS error correction algorithm is related to the number of primitive polynomials.","For example, if the order of a primitive polynomials is 8, then the number of elements in the GF is 2 8 , i.e., 256, the elements in the GF are used for a lookup table in the RS error correction calculation process, and the number of elements in the lookup table reaches 256; and if the order of a primitive polynomial is 16, then the number of elements in the GF is 2 16 , i.e., 65536, which occupies more memory space, and therefore the speed of data processing is slow and the application thereof is limited.","In addition, if the number of actual error code words exceeds the error correction capacity, a situation that more errors occur as the error correction proceeds may arise.","In addition, in conventional RS error correction algorithms, the error codes are not checked after being found and corrected, so the stability and correctness of the system is not high.","Chinese invention patent publication No.","CN1303763C discloses a method for reducing the complexity of encoding and decoding RS codes.","The invention has the following main features: when encoding at a sending terminal, the code element of the RS code is represented by the power of the primitive field element a, and code words of the RS codes are all in the finite field GF (2 m ), and all non-zero elements in the finite field GF (2 m ) are integer powers of the primitive field element α.","In coding and decoding, for any two elements X and Y in the finite field GF (2 m ), multiplication of X and Y equals to addition of the corresponding two exponents, and the addition and subtraction of X and Y are performed using a lookup table.","In this way, the coding and decoding method is improved based on existing RS coding and decoding algorithms, the complicated multiplication operation can be avoided and the coding and decoding speed is improved.","However, for the finite field GF (2 m ), three lookup tables have to be established, i and x′ in each group are stored in two long lookup tables, power [ ] and index [ ], and there is a further lookup table f(s), where s is selected from all the integers ranging from 0 to 2 m −1, with a total number of 2 m .","While the calculation speed is fast, the data memory occupied is relatively large, and after the RS error codes are corrected using the redundant codes, no valid data are used for checking, resulting in low security and stability."],[" SUMMARY OF THE INVENTION The technical problem to be addressed by the present invention is to provide a RS error correction decoding method which occupies less memory.","In order to address the above technical problem, the invention provides the following technical solutions: A RS error correction decoding method, in which, when encoding at a sending terminal, code words of information data are represented by K l , code words of redundant codes are represented by T, the order of primitive polynomial P(x) is m, a generator polynomial in GF(2 m ) is G(x), and an error correction code is represented by (c, k, t), wherein c is the total length of the information data and the redundant code, k is the length of the information data, and t is the length of the redundant code, then the code word polynomial Q(x) can be represented as Q ( x ) = ∑ l = t t + k - 1 K l · x l + ∑ n = 0 t - 1 T n · x n ; root of the m-order primitive polynomial P(x) is primitive field element in GF (2 m ), and the primitive field element is represented by α, thus the generator polynomial G(x) can be represented as G ( x ) = ∏ t = 1 t ( x - α i ) ; a lookup table f(α j ) is established for different power exponents of α, wherein the value of j is selected from all the integers ranging from 0 to 2m−1, with a total number of 2m; the generator polynomial G(x) is expanded to obtain a polynomial with respect to x, wherein the coefficients of the generator polynomial G(x) are the addition or subtraction of the power exponents of α; numerical values of the different power exponents of α are found out through the lookup table f(α j ) and the coefficients of the generator polynomial G(x) are calculated; it is assumed that the code words T of the redundant codes are all 0, then a code word polynomial Q ( x ) = ∑ l = t t + k - 1 K l · x l is obtained; the code word polynomial Q(x) is divided by the generator polynomial G(x) to obtain a remainder polynomial R ( x ) = ∑ i = 0 2 s T i · x i ; the coefficients Ti of R(x) are the addition or subtraction of the power exponents of α; numerical values of the power exponents of α are found out through the lookup table f(α j ), and the coefficients of the remainder polynomial R(x) are calculated, namely, the code words Tn of the redundant codes.","The invention has the following advantageous effects: a lookup table f(α j ) consisting of 2m exponents of the primitive field element α is established in the finite field GF (2 m ) to calculate the coefficients of the generator polynomial G(x) and the coefficients of the remainder polynomial R(x) obtained by dividing the code word polynomial Q(x) by the generator polynomial G(x), and the number of data in the lookup table f(α j ) is greatly reduced, thus saving a great deal of system memory and improving the flexibility and convenience in applying the RS error correction algorithm."],["CROSS REFERENCE TO RELATED APPLICATIONS The present application is a Continuation Application of PCT Application No.","PCT/CN2016/091012 filed on Jul.","22, 2016, which claims the benefit of Chinese Patent Application No.","201510461188.4 filed on Jul.","31, 2015.All the above are hereby incorporated by reference.","FIELD OF THE INVENTION The present invention relates to the technical field of error correction codes, and in particular to a Reed-Solomon (RS) error correction decoding method.","BACKGROUND OF THE INVENTION In a communication system, it is necessary to artificially add redundant codes to the data stream according to certain rules before information is sent so that a receiving terminal can detect and correct error codes.","RS error correction code is currently one of the most effective and widely used error control encoding measures.","RS codes can be used to correct random errors, and are also suitable for correcting burst errors, and have been widely used in areas such as satellite communications, digital television transmission or the like.","(c, k, 2t) are typically used to represent RS codes; where c is the total length of information data and redundant code, k is the length of the information data, 2t is the length of the redundant code, and t is the maximum number of errors that can be corrected, where c=K+2t.","The number of elements in the Galois field (GF) in the conventional RS error correction algorithm is related to the number of primitive polynomials.","For example, if the order of a primitive polynomials is 8, then the number of elements in the GF is 28, i.e., 256, the elements in the GF are used for a lookup table in the RS error correction calculation process, and the number of elements in the lookup table reaches 256; and if the order of a primitive polynomial is 16, then the number of elements in the GF is 216, i.e., 65536, which occupies more memory space, and therefore the speed of data processing is slow and the application thereof is limited.","In addition, if the number of actual error code words exceeds the error correction capacity, a situation that more errors occur as the error correction proceeds may arise.","In addition, in conventional RS error correction algorithms, the error codes are not checked after being found and corrected, so the stability and correctness of the system is not high.","Chinese invention patent publication No.","CN1303763C discloses a method for reducing the complexity of encoding and decoding RS codes.","The invention has the following main features: when encoding at a sending terminal, the code element of the RS code is represented by the power of the primitive field element a, and code words of the RS codes are all in the finite field GF (2m), and all non-zero elements in the finite field GF (2m) are integer powers of the primitive field element α.","In coding and decoding, for any two elements X and Y in the finite field GF (2m), multiplication of X and Y equals to addition of the corresponding two exponents, and the addition and subtraction of X and Y are performed using a lookup table.","In this way, the coding and decoding method is improved based on existing RS coding and decoding algorithms, the complicated multiplication operation can be avoided and the coding and decoding speed is improved.","However, for the finite field GF (2m), three lookup tables have to be established, i and x′ in each group are stored in two long lookup tables, power [ ] and index [ ], and there is a further lookup table f(s), where s is selected from all the integers ranging from 0 to 2m−1, with a total number of 2m.","While the calculation speed is fast, the data memory occupied is relatively large, and after the RS error codes are corrected using the redundant codes, no valid data are used for checking, resulting in low security and stability.","SUMMARY OF THE INVENTION The technical problem to be addressed by the present invention is to provide a RS error correction decoding method which occupies less memory.","In order to address the above technical problem, the invention provides the following technical solutions: A RS error correction decoding method, in which, when encoding at a sending terminal, code words of information data are represented by Kl, code words of redundant codes are represented by T, the order of primitive polynomial P(x) is m, a generator polynomial in GF(2m) is G(x), and an error correction code is represented by (c, k, t), wherein c is the total length of the information data and the redundant code, k is the length of the information data, and t is the length of the redundant code, then the code word polynomial Q(x) can be represented as Q ( x ) = ∑ l = t t + k - 1 K l · x l + ∑ n = 0 t - 1 T n · x n ; root of the m-order primitive polynomial P(x) is primitive field element in GF (2m), and the primitive field element is represented by α, thus the generator polynomial G(x) can be represented as G ( x ) = ∏ t = 1 t ( x - α i ) ; a lookup table f(αj) is established for different power exponents of α, wherein the value of j is selected from all the integers ranging from 0 to 2m−1, with a total number of 2m; the generator polynomial G(x) is expanded to obtain a polynomial with respect to x, wherein the coefficients of the generator polynomial G(x) are the addition or subtraction of the power exponents of α; numerical values of the different power exponents of α are found out through the lookup table f(αj) and the coefficients of the generator polynomial G(x) are calculated; it is assumed that the code words T of the redundant codes are all 0, then a code word polynomial Q ( x ) = ∑ l = t t + k - 1 K l · x l is obtained; the code word polynomial Q(x) is divided by the generator polynomial G(x) to obtain a remainder polynomial R ( x ) = ∑ i = 0 2 s T i · x i ; the coefficients Ti of R(x) are the addition or subtraction of the power exponents of α; numerical values of the power exponents of α are found out through the lookup table f(αj), and the coefficients of the remainder polynomial R(x) are calculated, namely, the code words Tn of the redundant codes.","The invention has the following advantageous effects: a lookup table f(αj) consisting of 2m exponents of the primitive field element α is established in the finite field GF (2m) to calculate the coefficients of the generator polynomial G(x) and the coefficients of the remainder polynomial R(x) obtained by dividing the code word polynomial Q(x) by the generator polynomial G(x), and the number of data in the lookup table f(αj) is greatly reduced, thus saving a great deal of system memory and improving the flexibility and convenience in applying the RS error correction algorithm.","BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWINGS FIG.","1 is a flowchart of performing RS encoding by a sending terminal according to a first embodiment of the present invention; and FIG.","2 is a flowchart of RS encoding and error correction according to the first embodiment of the present invention.","DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The disclosure, objects and effects of the present invention will be described in detail below with reference to the embodiments and accompanying drawings.","The critical concept of the present invention is to establish a lookup table f(αj) for different power exponents of α for a m-order primitive polynomial P(x), where j is selected from all the integers ranging from 0 to 2m−1, with a total number of 2m, for the calculation of coefficients of a generator polynomial G(x) and coefficients of a remainder polynomial R(x) obtained by dividing a code word polynomial Q(x) by the generator polynomial G(x), thus greatly saving the system memory; and a redundant code is additionally taken during encoding, for checking the data obtained by error correction decoding so as to improve system correctness and stability.","The technical term involved in the present invention is explained in Table 1: TABLE 1 Technical term Interpretation polynomial A number is represented by a sum of a group of bases (1, representation α, α2, .",".",".",", αn−1), and the group of bases are referred to as standard bases Referring to FIG.","1 and FIG.","2, a specific embodiment of the present invention is described as follows.","A RS error correction decoding method is provided, in which, when encoding at a sending terminal, code words of information data are represented by Kl, code words of redundant codes are represented by Tn, the order of primitive polynomial P(x) is m, a generator polynomial in GF(2m) is G(x), and an error correction code is represented by (c, k, t), wherein c is the total length of the information data and the redundant code, k is the length of the information data, and t is the length of the redundant code, then the code word polynomial Q(x) can be represented as Q ( x ) = ∑ l = t t + k - 1 K l · x l + ∑ n = 0 t - 1 T n · x n ; root of the m-order primitive polynomial P(x) is primitive field element in GF (2m), and the primitive field element is represented by α, thus the generator polynomial G(x) can be represented as G ( x ) = ∏ i = 1 t ( x - a i ) ; a lookup table f(αj) is established for different power exponents of α, wherein the value of j is selected from all the integers ranging from 0 to 2m−1, with a total number of 2m; the generator polynomial G(x) is expanded to obtain a polynomial with respect to x, wherein the coefficients of the generator polynomial G(x) are the addition or subtraction of the power exponents of α; numerical values of the different power exponents of α are found out through the lookup table f(αj) and the coefficients of the generator polynomial G(x) are calculated; it is assumed that the code words Tn of the redundant codes are all 0, then a code word polynomial Q ( x ) = ∑ l = t t + k - 1 K l · x l is obtained; the code word polynomial Q(x) is divided by the generator polynomial G(x) to obtain a remainder polynomial R ( x ) = ∑ i = 0 2 s T i · x i ; the coefficients Ti of R(x) are the addition or subtraction of the power exponents of α; numerical values of the power exponents of α are found out through the lookup table f(αj), and the coefficients of the remainder polynomial R(x) are calculated, namely, the code word Tn of the redundant codes.","Further, the error correction decoding process is described as follows: it is assumed that s is the maximum number of error correction bits of a receiving terminal, let t=2s+1; the code word polynomial Q(x) is divided by the generator polynomial G(x) to obtain the remainder polynomial R(x), R ( x ) = ∑ i = 0 2 s T i · x i ; the coefficients of the remainder polynomial R(x) are calculated, thus obtaining the code words Tn of 2s+1 redundant codes, n=1, 2, .",".",".",", 2s+1; the sending terminal sends information data and 2s+1 redundant codes to the receiving terminal; the receiving terminal receives the information data and 2s+1 redundant codes; the receiving terminal obtains the code word polynomial Q(x) by coding according to the received information data and 2s+1 redundant codes, and the code word polynomial Q(x) is represented as Q ( x ) = ∑ l = 2 s + 1 2 s + k K l · x l + ∑ n = 0 2 s T n · x n ; the receiving terminal calculates 2s+1 correctors Si, where Si=Q(αi), i=1, 2, .",".",".",", 2s+1; a location and a correction value of error information code are calculated using correctors Sito S2s if not all of the correctors S, are equal to 0; the correction value is added to the code word at the location of the error information code received by the receiving terminal to obtain an error-corrected code word; the value of the error-corrected code word is assigned to the code word at the location of the error information code; S2s+1=Q(α2s+1) is recalculated, and if S2s+1=0, the error correction is successful, and if S2s+1≠0, received information code error is output and the error correction capacity is insufficient for this.","As can be seen from the above description, 2s+1 redundant codes are obtained when the 0th power of x is taken in calculating the redundant codes, and after the error correction codes are calculated using the 1st to the 2sth redundant codes, the (2s+1)th redundant code is used to check whether the error-corrected code word polynomial is correct.","In this way, the correctness of the error correction operation is effectively ensured, and the stability of system operation is improved.","Further, in the process of obtaining the remainder polynomial R(x) by dividing the code word polynomial Q(x) by the generator polynomial G(x), multiplication of the coefficients of x will be performed, and the multiplication is converted into addition in operation as follows.","the coefficients of x are represented by a polynomial representation; the coefficients represented by the polynomial representation are multiplied and expanded to obtain addition of different power exponents of α; the numerical values of the different power exponents of α are found out by looking up the lookup table f(αj) so as to solve the addition.","Further, the specific process of calculating the location of the error information code using the correctors S1 to S2s is described as follows: a calculation is performed based on the correctors to obtain an equation taking the location of the error information code as a root; the root of the equation is represented by a polynomial representation, with standard bases being different power exponents of α and coefficients being values of Xi, where i=0, 1, .",".",".",", m; the coefficients of the equation are represented by a polynomial representation, with standard bases being different power exponents of α; the root and coefficients represented by the polynomial representations are brought into the polynomial of the equation; let the coefficient of each term of the polynomial be zero, thus obtaining a non-homogeneous linear equations set for xi; the non-homogeneous linear equation set is solved to obtain the value of xi; the value of xi is brought into the root represented by the polynomial representation to calculate the root of the equation and obtain the location of the error information code; the location in the code word polynomial Q(x) corresponding to the location of the error information code is looked for.","Further, looking for the location in the code word polynomial Q(x) corresponding to the location of the error information code is specifically as follows: a numerical value that is the same as the value of the error information code is looked for in the lookup table f(αj), and the coefficient at the location where the exponent value of x in the polynomial Q(x) is equal to the exponent value of α corresponding to the numerical value is the location in the code word polynomial Q(x) corresponding to the error information code; if the numerical value that is the same as the value of the error information code is not found in the lookup table f(αj), the following method is used to find out the location of the error information code, specifically: in step S1, take p=2*m−1=31, v=α2m−1; in step S2, let p=p+1; in step S3, if the highest data bit of v is 1, v is firstly shifted leftward by 1 bit, and then v=v+v0, where v0 is the numerical value obtained by bringing x=α into the primitive polynomial P(x) except for the term of the highest power of x; if the highest data bit of v is 0, v is shifted leftward by 1 bit; in step S4, the v obtained in step S3 is compared with the error information code to see if they are equal: if the v is equal to the error information code, the coefficient corresponding to the pth power of x in the code word polynomial Q (x) is the location of the error information code; and If the v is not equal to the error information code, then turn to step S2 to continue the process.","Further, using the correctors S1 to S2s to calculate the correction value is specifically as follows: a equation set consisting of the location of the error information code and the correction value is obtained, where the error information code is the root of the equation set, and the correction value is an unknown number of the equation set; the correction value of the equation set is represented by the polynomial representation, with standard bases being different power exponents of α, and coefficients being values of xi, i=0, 1, .",".",".",", m; the location of the error information code of the equation set is represented by the polynomial representation, with standard bases being different power exponents of α; the correction value and coefficients represented by the polynomial representation are brought into the polynomial of the equation set; let the coefficient of each term of the polynomial be zero, thus obtaining a non-homogeneous linear equation set for xi; the non-homogeneous linear equation set is solved to obtain the value of xi; the value of xi is brought into the correction value represented by the polynomial representation so as to calculate the root of the equation set and obtain the correction value.","It can be seen from the above description that in the process of error correction decoding of RS operation, the coefficients and unknown numbers of polynomials are all represented by the polynomial representation, thus the multiplication operation can be converted into addition operation, and solving of equation or equation set can be converted into solving of the non-homogeneous linear equation set so that the complicated operations are simplified, and the calculation process is simplified.","The requirements on hardware are reduced, and the correctness of system operation is improved.","If the numerical value that is being looked for is beyond the numerical value range of the lookup table f(αj), the numerical value can be calculated by exponential operation.","Since the data beyond the numerical value range of the lookup table f(αj) is less in the process of RS error correction decoding, only 2m data are established in the lookup table f(αj), and the memory consumption is therefore reduced.","Referring to FIG.","1 and FIG.","2, the first embodiment of the present invention is described as follows.","A RS error correction decoding method is provided, in which when encoding at a sending terminal, five code words of information data, 0x1234, 0x5678, 0x3245, 0xabcd, 0xef10, are represented by Kl, l=5, and the primitive polynomial is P(x)=x16+x5+x3+x2+1, the order of the primitive polynomial is 16, and for a generator polynomial in the GF(216), k is the length of information data, then, k is 5, t is the length of the redundant code, s is the maximum number of error correction bits by the receiving end and is 2; when taking t=2s+1, then t=5, c is the total length of the information data and the redundant code and is 10, the error correction code is represented by (c, k, t), then (c, k, t) is (10, 5, 5), Tn represents the code words of the redundant codes, n=1, 2, .",".",".",", 5, then the code word polynomial Q(x) can be represented as Q ( x ) = ∑ l = t t + k - 1 K l · x l + ∑ n = 0 t - 1 T n · x n ; a root of the 16-order primitive polynomial P(x) is a primitive field element in GF (216), and the primitive field element is represented by α, then the generator polynomial G(x) can be represented as G ( x ) = ∏ i = 1 5 ( x - α i ) ; a lookup table f(αj) for different power exponents of α is established, where the value of j is selected from all the integers ranging from 0 to 31, with a total number of 2m, specifically: {1,2,4,8,0x10,0x20,0x40,0x80,0x100,0x200,0x400,0x800,0x1000,0x2000, 0x4000,0x8000,0x2d,0x5a,0xb4,0x168.0x2d0,0x5a0,0xb40,0x1680,0x2d00, 0x5a00,0xb400,0x682d,0xd05a,0xa099,0x411f,0x8233}; the generator polynomial G(x) is expanded to obtain a polynomial with respect to x, where the coefficients of the generator polynomial G(x) are addition or subtraction of the power exponents of α, specifically: G ( x ) = ∏ i = 1 5 ( x - α i ) = ( x - α ) ( x - α 2 ) ( x - α 3 ) ( x - α 4 ) ( x - α 5 ) = x 5 + ( α + α 2 + α 3 + α 4 + α 5 ) x 4 + ( α 3 + α 4 + α 8 + α 9 ) x 3 + ( α 7 + α 8 + α 11 + α 12 ) x 2 + ( α 10 + α 11 + α 12 + α 13 + α 14 ) x + α 15 ; numerical values of the different power exponents of α are found out through the lookup table f(αj) and the coefficients of the generator polynomial G(x) are calculated, specifically: G(x)=x5+0x3e*x4+0x318*x3+0x18c0*x2+0x7c00*x+0x8000; it is assumed that each code word Tn of the redundant codes is 0, then the code word polynomial Q ( x ) = ∑ l = t t + k - 1 K l · x l is obtained, specifically: Q(x)=0x1234*x9+0x5678*x8+0x3245*x7+0xabcd*x6+0xef10*x5+0*x4+0*x3+0*x2+0* x1+0*x0; the code word polynomial Q(x) is divided by the generator polynomial G(x) to obtain a remainder polynomial R ( x ) = ∑ i = 0 2 s T i · x i .","In calculating the remainder polynomial R(x), multiplication of coefficients of x will be performed, and the multiplication operation is converted into addition operation, specifically: 0x1234*0x18c0 is taken as an example; the coefficients of x in the code word polynomial Q(x) and the generator polynomial G(x) are represented by a polynomial representation, specifically: 0x1234=0*α15+0*α14+0*α13+1*α12+0*α11+0*α10+1*α9+0*α8+0*α7+0*α6+1*α5+1*α4+0*α3+1*α2+0*α1+0*α0=α12+α9+α5+α4+α2; 0x18c0=0*α15+0*α14+0*α13+1*α12+1*α11+0*α10+0*α9+0*α8+1*α7+1*α6+0*α5+0*α4+0*α3+0*α2+0*α1+0*α0=α12+α11+α7+α6; the coefficients represented by the polynomial representation are multiplied and expanded to obtain addition of different power exponents of α: 0 x 1234 * 0 x 18 c 0 = ( α 12 + α 9 + α 5 + α 4 + α 2 ) * ( α 12 + α 11 + α 7 + α 6 ) = α 24 + α 21 + α 17 + α 16 + α 14 + α 23 + α 20 + α 16 + α 15 + α 13 + α 19 + α 16 + α 12 + α 11 + α 9 + α 18 + α 15 + α 11 + α 10 + α 8 = α 24 + α 23 + α 21 + α 20 + α 19 + α 18 + α 17 + α 16 + α 14 + α 13 + α 12 + α 10 + α 9 + α 8 = 0 x 2 d 00 + 0 x 1680 + 0 x 5 a 0 + 0 x 2 d 0 + 0 x 168 + 0 x b 4 + 0 x 5 a + 0 x 2 d + 0 x 4000 + 0 x 2000 + 0 x 1000 + 0 x 400 + 0 x 200 + 0 x 100 = 0 x 4 a 5 b ; the numerical values of the power exponents of α are found out through the lookup table f(αj), and the coefficients of the remainder polynomial R(x), i.e., the code words of the redundant codes Tn, n=1, 2, .",".",".",", 5, are calculated; the remainder polynomial R(x) is obtained: |R(x)=0x15d4*x4+0x2606*x3+0x3587*x2+0x417e*x1+0x121c*x0; code words of the five redundant codes are 0x15d4, 0x2606, 0x3587, 0x417e, 0x121c; the sending terminal sends five information data and five redundant codes 0x1234, 0x5678, 0x3245, 0xabcd, 0xef10, 0x15d4, 0x2606, 0x3587, 0x417e, 0x121c to the receiving terminal.","It is assumed that the third information data and the third redundant code received by the receiving terminal are in error, then the information data and the redundant codes received by the receiving terminal are 0x1234, 0x5678, 0xe305, 0xabcd, 0xef10, 0x15d4, 0x2606, 0xa513, 0x417e , 0x121c.","The code word polynomial Q(x) obtained by the receiving terminal according to the received information data and redundant codes is: Q(x)=0x1234*x9+0x5678*x8+0xe305*x7+0xabcd*x6+0xef10* x5+0x15d4*x4+0x2606*x3+0x513*x2+0x417e*x1+0x121c*x0.The receiving terminal calculates five correctors Si, where Si=Q(αi), i=1, 2, .",".",".",", 5, specifically, S1=Q(α1)=0xed82; S2=Q(α2)=0xc556; S3=Q(α3)=0x879a; S4=Q(α4)=0x4eb7; S5=Q(α5)=0x7cb9; if not all of the correctors Si are equal to 0, then the location of the error information code and the correction value are calculated using the correctors S1 to S2s; specifically, calculation is performed according to the correctors to obtain the equation SS2·x2+SS1·x+SS0=0, and the root of the equation is the location of the error code.","Let s1=(s1 s2), s2=(s2 s3), s3=(s3 s4), then SS2=|S1T S2T|=S2*S2+S1*S3=0x219f; SS1=|S1T S3T|=S4*S1+S3*S2=0x4b2c; SS0=|S2T S1T|=S4*S2+S3*S3=0x3537; then the equation is 0x219f·x2+0x4b2c·|x+0x3537=0, and the solution to this equation is as follows: the roots of the equation are represented by the polynomial representation, that is, x and x2 are represented by the polynomial representation as: x=x15α15+x14α14+x13α13+x12α12+x11α11+x10α10+x9α9+x8α8+x7α7+x6α6+x5α5+x|4α4x3α3+x2α2+x1α1x0α0; x2=x15α30+x14α28+x13α26+x12α24+x11α22+x10α20+x9α18+x8α16+x7α14+x6α12+x5α10+x4α8+x3α6+x2α4+x1α2+x0α0; where xi can only take 0 or 1, i=1, 2, .",".",".",", 15; the values of x and x2 are brought into the left of the equation to obtain 0x219f*x2+0x4b2c*x+0x3537=0xe006x15+0xe5c6x14+0x1799x13+0x1292x12+0x 2f1bx12+0x1e19x10+0x2d6cx9+0xbe3dx8+0x3537x7+0x6d1fx6+0 xoeabx5+0x28f9x4+0x3f92x3+0x3527x2+0x1024x1+0x6ab3x0; the exponents of α corresponding to the coefficients of xi are looked for in the lookup table f(αj), and the left side of the equation is converted into the expression of the exponents of α and xi, specifically: 0x219f*x2+0x4b2c*x+0x3537 =0xe006x15+0xe5c6x14+0x1799x13+0x1292x12+0x2f1bx11 +0x1e19x10+0x2d6cx9+0xbe3dx8+0x3537x7+0x6d1fx6 +0xoeabx5+0x28f9x4+0x3f92x3+0x3527x2+0x1024x1+0x6ab3x0 =(x0+x2+x4+x5+x6+x7+x8+x10+x11+x13+1)*α0 +(x0+x2+x3+x5+x6+x7+x11+x12+x14+x15+1)*α1 +(x1+x2+x6+x7+x8+x9+x14+x15+1)*α2 +(x4+x5+x6+x8+x9+x10+x11+x13+0)*α3 +(x0+x2+x3+x4+x6+x7+x8+x10+x11+x12+x13+1)*α4 +(x0+x1+x2+x4+x5+x7+x8+x9+1)*α5 +(x4+x9+x14+0)*α6 +(x0+x3+x4+x5+x12+x13+x14+0)*α7 +(x2+x3+x7+x9+x11+x13+x14+1)*α8 +(x0+x3+x5+x8+x10+x11+x12+x13+0)*α9 +(x2+x3+x5+x7+x8+x9+x10+x11+x13+x14+1)*α10 +(x0+x3+x4+x5+x8+x9+x10+x11+0)*α11 +(x1+x2+x3+x7+x8+x10+x12+x13+1)*α12 +(x0+x2+x3+x4+x6+x7+x8+x9+x11+x14+x15+1)*α13 +(x0+x6+x14+x15+0)*α14 +(x8+x14+x15+0)*α15; let all the above coefficients of αi be equal to 0, thus obtaining 16 equations: x0+x2+x4+x5+x6+x7+x8+x10+x11+x13=1; x0+x2+x3+x5+x6+x7+x11+x12+x14+x15=1; x1+x2+x6+x7+x8+x9+x14+x15=1; x4+x5+x6+x8+x9+x10+x11+x13=0; x0+x2+x3+x4+x6+x7+x8+x10+x11+x12+x13=1; x0+x1+x2+x4+x5+x7+x8+x9=1; x4+x9+x14=0; x0+x3+x4+x5+x12+x13+x14=0; x2+x3+x7+x9+x11+x13+x14=1; x0+x3+x5+x8+x10+x11+x12+x13=0; x2+x3+x5+x7+x8+x9+x10+x11+x13+x14=1; x0+x3+x4+x5+x8+x9+x10+x11=0; x1+x2+x3+x7+x8+x10+x12+x131; x0+x2+x3+x4+x6+x7+x8+x9+x11+x14+x151; x0+x6+x14+x15=0; x8+x14+x15=0; the above 16 equations are converted into a non-homogeneous linear equation set for xi, and a matrix consisting of the coefficients of xi′ and numerical values of constant terms is obtained: [ 1 0 1 0 1 1 1 1 1 0 1 1 0 1 0 0 1 1 0 1 1 0 1 1 1 0 0 0 1 1 0 1 1 1 0 1 1 0 0 0 1 1 1 1 0 0 0 0 1 1 1 0 0 0 0 1 1 1 0 1 1 1 1 0 1 0 0 0 1 0 1 1 1 0 1 1 1 0 1 1 1 1 0 0 1 1 1 1 0 1 1 0 1 1 1 0 0 0 0 0 0 1 0 0 0 0 1 0 0 0 0 1 0 0 0 0 1 0 0 1 0 0 1 1 1 0 0 0 0 0 0 1 1 1 0 0 0 0 1 1 0 0 0 1 0 1 0 1 0 1 1 0 1 1 0 0 1 0 1 0 0 1 0 1 1 1 1 0 0 0 0 0 1 1 0 1 0 1 1 1 1 1 0 1 1 0 1 1 0 0 1 1 1 0 0 1 1 1 1 0 0 0 0 0 0 1 1 1 0 0 0 1 1 0 1 0 1 1 0 0 1 1 0 1 1 1 0 1 1 1 1 0 1 0 0 1 1 1 1 0 0 0 0 0 1 0 0 0 0 0 0 0 1 1 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 1 1 0 ] ; the above non-homogeneous linear equation set is solved to obtain x1=0x0004, x2=0x0080; in the lookup table f(αj), the locations corresponding to x1 and x2 are the second power of α and the seventh power of α respectively; thus, the locations of the error information codes in the code word polynomial Q(x) are the coefficients corresponding to the second power and the seventh power of x, namely, 0xa513 and 0xe305.If no values that are the same as the values of x1 and x2 are found in the lookup table f(αj), the following method is used to find out the location of the error code, specifically: in step S1, take p=2*m−1=31, v=α2m−1=0x823e; in step S2, let p=p+1; in step S3, if the highest data bit of v is 1, v is firstly shifted leftward by 1 bit, and then v=v+0x1d, where 0x1d is the numerical value obtained by bringing x=α into x5+x3+x2+1 in the primitive polynomial P(x)=x16+x5+x3+x2+1; if the highest data bit of v is 0, v is shifted leftward by 1 bit; in step S4, the v obtained in step S3 is compared with x1 or x2 to see if they are equal: if the v is equal to x1 or x2, the coefficient corresponding to the pth power of x in the code word polynomial Q (x) is the location of the error information code; and If the v is not equal to x1 or x2, then turn to step S2 to continue the process.","The error value is calculated according to the following two equations: S1=e1·x1+e2·x2=0xed82; S2=e1·x12+e2·x22=0xc556; values of x1 and x2 are brought into the above two equations to yield e1=0x9094 and e2=0xd140, specifically: S1*x1−S2 is calculated to yield (x1·x2−x22)·e2=0xed82=0xc556; e2 is represented in polynomial representation as: e2=x15α15+x14α14+x13α13+x12α12+x11α11+x10α10+x9α9+x8α8+x7α7+x6α6+x5α5+x4α4+x3α3+x2α2+x1α1+x0α0; where xi can only take 0 or 1, i=1, 2, .",".",".",", 15; the value of e2 is brought into (x1·x2−x22)·e2=0xed82−0xc556 to obtain the non-homogeneous linear equation set and yield e2=0xd140; and in a similar principle, yield e1=0x9094; the correction value is added to the code word at the location of the error information code received by the receiving terminal to obtain error-corrected code word, specifically: in the error-corrected code word polynomial Q(x), the coefficient of the second power of x is: 0xa513+0x9094=0x3587, and the coefficient of the seventh power of x is: 0xe305+0xd140=0x3245; the value of the error-corrected code word is assigned to the code word at the location of the error information code so as to obtain the error-corrected code word polynomial Q(x) as follows: Q(x)=0x1234*x9+0x5678*x8+0x3245*x7+0xabcd*x6+0xef10*x5+0x15d4*x4+0x2606*x3+0x3587*x2+0x417e*x1+0x121c*x0; S5=Q(α5) is recalculated, and if S5=0 is yielded, the error correction is successful.","To sum up, in the RS error correction decoding method according to the present invention, a lookup table f(αj) for different power exponents of α is established, where j is selected from all the integers ranging from 0 to 2m−1, and with a total number of 2m, for the calculation of the coefficients of the generator polynomial G(x) and the coefficients of the remainder polynomial R(x) obtained by dividing the code word polynomial Q(x) by the generator polynomial G(x), thus greatly saving system memory; one additional redundant code is taken in encoding, for the purpose of checking the data obtained after the error correction decoding, thereby improving correctness and stability of the system."]],"string":"[\n [\n \"RS ERROR CORRECTION DECODING METHOD\",\n \"A decoding method includes that when encoding at a sending terminal, for a m-order primitive polynomial P(x), a primitive field element in galois field GF(2m) is represented by α; a lookup table f(αj) for different power exponents of α is established, where the value of j is selected from all the integers ranging from 0 to 2m−1, with a total number of 2m; a generator polynomial G(x) is expanded to obtain a polynomial with respect to x, with coefficients being an addition or subtraction of the power exponents of α; a remainder polynomial R(x), obtained by dividing code word polynomial Q(x) by the generator polynomial G(x), is a polynomial with respect to x, with coefficients being an addition or subtraction of the power exponents of α; and the coefficients of the generator polynomial G(x) and the remainder polynomial R(x) are both calculated using data found in the lookup table f(αj).\"\n ],\n [\n \"1.A RS error correction decoding method, characterized in that, when encoding at a sending terminal, code words of information data are represented by Kl, code words of redundant codes are represented by Tn, the order of primitive polynomial P(x) is m, a generator polynomial in GF(2m) is G(x), and an error correction code is represented by (c, k, t), wherein c is the total length of the information data and the redundant code, k is the length of the information data, and t is the length of the redundant code, then the code word polynomial Q(x) can be represented as Q ( x ) = ∑ l = t t + k - 1 K l · x l + ∑ n = 0 t - 1 T n · x n ; root of the m-order primitive polynomial P(x) is primitive field element in GF (2m), and the primitive field element is represented by α, thus the generator polynomial G(x) can be represented as G ( x ) = ∏ i = 1 t ( x - α i ) ; a lookup table f(αj) is established for different power exponents of α, wherein the value of j is selected from all the integers ranging from 0 to 2m−1, with a total number of 2m; the generator polynomial G(x) is expanded to obtain a polynomial with respect to x, wherein the coefficients of the generator polynomial G(x) are the addition or subtraction of the power exponents of α; numerical values of the different power exponents of α are found out through the lookup table f(αj) and the coefficients of the generator polynomial G(x) are calculated; it is assumed that the code words Tn of the redundant codes are all 0, then a code word polynomial Q ( x ) = ∑ l = t t + k - 1 K l · x l is obtained; the code word polynomial Q(x) is divided by the generator polynomial G(x) to obtain a remainder polynomial R ( x ) = ∑ i = 0 2 s T i · x i ; the coefficients Ti of R(x) are the addition or subtraction of the power exponents of α; numerical values of the power exponents of α are found out through the lookup table f(αj), and the coefficients of the remainder polynomial R(x) are calculated, namely, the code words Tn of the redundant codes.\",\n \"2.The RS error correction decoding method according to claim 1, wherein the error correction decoding process includes: assuming that s is the maximum number of error correction bits of the receiving terminal, let t=2s+1; dividing the code word polynomial Q(x) by the generator polynomial G(x) to obtain the remainder polynomial R(x), R ( x ) = ∑ i = 0 2 s T i · x i ; calculating the coefficients of the remainder polynomial R(x), thus obtaining the code words Tn of 2s+1 redundant codes, n=1, 2, .\",\n \".\",\n \".\",\n \", 2s+1; sending, by the sending terminal, information data and 2s+1 redundant codes to the receiving terminal; receiving, by the receiving terminal, the information data and 2s+1 redundant codes; obtaining, by the receiving terminal, the code word polynomial Q(x) according to the received information data and 2s+1 redundant codes, and the code word polynomial Q(x) being represented as: Q ( x ) = ∑ l = 2 s + 1 2 s + k K l · x l + ∑ n = 0 2 s T n · x n ; calculating, by the receiving terminal, 2s+1 correctors Si, wherein Si=Q(αi), i=1, 2, .\",\n \".\",\n \".\",\n \", 2s+1; calculating a location of an error information code and a correction value using correctors S1to S2s, if not all of the correctors S, are equal to 0; adding the correction value to the code word at the location of the error information code received by the receiving terminal to obtain an error-corrected code word; assigning the value of the error-corrected code word to the code word at the location of the error information code; recalculating S2s+1=Q(α2s+1), wherein if S2s+1=0, the error correction is successful.\",\n \"3.The RS error correction decoding method according to claim 1, wherein in the process of obtaining the remainder polynomial R(x) by dividing the code word polynomial Q(x) by the generator polynomial G(x), multiplication of the coefficients of x is performed, and the multiplication operation is converted into addition operation specifically as follows: representing the coefficients of x by a polynomial representation; multiplying and expanding the coefficients represented by the polynomial representation to obtain an addition of different power exponents of α; finding out the numerical values of the different power exponents of α through the lookup table f(αj) to solve the addition.\",\n \"4.The RS error correction decoding method according to claim 1, wherein the process of calculating the location of the error information code using the correctors S1to S2s is specifically performed as follows: calculating according to the correctors to obtain an equation taking the location of the error information code as a root; representing the root of the equation by a polynomial representation, with standard bases being different power exponents of α and coefficients being values of Xi, wherein i=0, 1, .\",\n \".\",\n \".\",\n \", m; representing the coefficients of the equation by the polynomial representation, with standard bases being different power exponents of α; bringing the root and coefficients represented by the polynomial representation into the polynomial of the equation; letting the coefficient of each term of the polynomial be zero, thus obtaining a non-homogeneous linear equation set for xi; solving the non-homogeneous linear equation set to obtain the value of xi; substituting the value of xi into the root represented by the polynomial representation to obtain by calculation the root of the equation so as to obtain the location of the error information code; looking for the location in the code word polynomial Q(x) corresponding to the location of the error information code.\",\n \"5.The RS error correction decoding method according to claim 4, wherein looking for the location in the code word polynomial Q(x) corresponding to the location of the error information code specifically includes: finding out the numerical value in the lookup table f(αj) that is the same as the value of the error information code, the coefficient at the location where the exponent value of x in the polynomial Q(x) is equal to the exponent value of α corresponding to the numerical value is the location in the code word polynomial Q(x) corresponding to the error information code; if the numerical value that is the same as the value of the error information code is not found in the lookup table f(αj), the following method is used to find out the location of the error information code, specifically: S1, taking p=2*m−1=31, v=α2m−1; S2, letting p=p+1; S3, if the highest data bit of v is 1, shifting v leftward by 1 bit firstly, and then v=v+v0, wherein v0 is the numerical value obtained by bringing x=α into the primitive polynomial P(x) except for the term of the highest power of x; if the highest data bit of v is 0, shifting v leftward by 1 bit; S4, comparing the v obtained in step S3 with the error information code to see whether they are equal: If the v is equal to the error information code, the coefficient corresponding to the pth power of x in the code word polynomial Q (x) is the location of the error information code.\",\n \"If the v is not equal to the error information code, then turn to step S2 to continue the process.\",\n \"6.The RS error correction decoding method according to claim 4, wherein calculating the correction value using the correctors S1 to S2s is specifically as follows: obtaining a equation set consisting of the location of the error information code and the correction value, wherein the error information code is the root of the equation set, and the correction value is an unknown number of the equation set; representing the correction value of the equation set by the polynomial representation, with standard bases being different power exponents of α, and coefficients being values of xi, i=0, 1, .\",\n \".\",\n \".\",\n \", m; representing the location of the error information code of the equation set by the polynomial representation, with standard bases being different power exponents of α; bringing the correction value and coefficients represented by the polynomial representations into the polynomial of the equation set; letting the coefficient of each term of the polynomial be zero, thus obtaining a non-homogeneous linear equation set for xi; solving the non-homogeneous linear equation set to obtain the value of xi; bringing the value of xi into the correction value represented by the polynomial representation to obtain by calculation the root of the equation set so as to obtain the correction value.\"\n ],\n [\n \" BACKGROUND OF THE INVENTION In a communication system, it is necessary to artificially add redundant codes to the data stream according to certain rules before information is sent so that a receiving terminal can detect and correct error codes.\",\n \"RS error correction code is currently one of the most effective and widely used error control encoding measures.\",\n \"RS codes can be used to correct random errors, and are also suitable for correcting burst errors, and have been widely used in areas such as satellite communications, digital television transmission or the like.\",\n \"(c, k, 2t) are typically used to represent RS codes; where c is the total length of information data and redundant code, k is the length of the information data, 2t is the length of the redundant code, and t is the maximum number of errors that can be corrected, where c=K+2t.\",\n \"The number of elements in the Galois field (GF) in the conventional RS error correction algorithm is related to the number of primitive polynomials.\",\n \"For example, if the order of a primitive polynomials is 8, then the number of elements in the GF is 2 8 , i.e., 256, the elements in the GF are used for a lookup table in the RS error correction calculation process, and the number of elements in the lookup table reaches 256; and if the order of a primitive polynomial is 16, then the number of elements in the GF is 2 16 , i.e., 65536, which occupies more memory space, and therefore the speed of data processing is slow and the application thereof is limited.\",\n \"In addition, if the number of actual error code words exceeds the error correction capacity, a situation that more errors occur as the error correction proceeds may arise.\",\n \"In addition, in conventional RS error correction algorithms, the error codes are not checked after being found and corrected, so the stability and correctness of the system is not high.\",\n \"Chinese invention patent publication No.\",\n \"CN1303763C discloses a method for reducing the complexity of encoding and decoding RS codes.\",\n \"The invention has the following main features: when encoding at a sending terminal, the code element of the RS code is represented by the power of the primitive field element a, and code words of the RS codes are all in the finite field GF (2 m ), and all non-zero elements in the finite field GF (2 m ) are integer powers of the primitive field element α.\",\n \"In coding and decoding, for any two elements X and Y in the finite field GF (2 m ), multiplication of X and Y equals to addition of the corresponding two exponents, and the addition and subtraction of X and Y are performed using a lookup table.\",\n \"In this way, the coding and decoding method is improved based on existing RS coding and decoding algorithms, the complicated multiplication operation can be avoided and the coding and decoding speed is improved.\",\n \"However, for the finite field GF (2 m ), three lookup tables have to be established, i and x′ in each group are stored in two long lookup tables, power [ ] and index [ ], and there is a further lookup table f(s), where s is selected from all the integers ranging from 0 to 2 m −1, with a total number of 2 m .\",\n \"While the calculation speed is fast, the data memory occupied is relatively large, and after the RS error codes are corrected using the redundant codes, no valid data are used for checking, resulting in low security and stability.\"\n ],\n [\n \" SUMMARY OF THE INVENTION The technical problem to be addressed by the present invention is to provide a RS error correction decoding method which occupies less memory.\",\n \"In order to address the above technical problem, the invention provides the following technical solutions: A RS error correction decoding method, in which, when encoding at a sending terminal, code words of information data are represented by K l , code words of redundant codes are represented by T, the order of primitive polynomial P(x) is m, a generator polynomial in GF(2 m ) is G(x), and an error correction code is represented by (c, k, t), wherein c is the total length of the information data and the redundant code, k is the length of the information data, and t is the length of the redundant code, then the code word polynomial Q(x) can be represented as Q ( x ) = ∑ l = t t + k - 1 K l · x l + ∑ n = 0 t - 1 T n · x n ; root of the m-order primitive polynomial P(x) is primitive field element in GF (2 m ), and the primitive field element is represented by α, thus the generator polynomial G(x) can be represented as G ( x ) = ∏ t = 1 t ( x - α i ) ; a lookup table f(α j ) is established for different power exponents of α, wherein the value of j is selected from all the integers ranging from 0 to 2m−1, with a total number of 2m; the generator polynomial G(x) is expanded to obtain a polynomial with respect to x, wherein the coefficients of the generator polynomial G(x) are the addition or subtraction of the power exponents of α; numerical values of the different power exponents of α are found out through the lookup table f(α j ) and the coefficients of the generator polynomial G(x) are calculated; it is assumed that the code words T of the redundant codes are all 0, then a code word polynomial Q ( x ) = ∑ l = t t + k - 1 K l · x l is obtained; the code word polynomial Q(x) is divided by the generator polynomial G(x) to obtain a remainder polynomial R ( x ) = ∑ i = 0 2 s T i · x i ; the coefficients Ti of R(x) are the addition or subtraction of the power exponents of α; numerical values of the power exponents of α are found out through the lookup table f(α j ), and the coefficients of the remainder polynomial R(x) are calculated, namely, the code words Tn of the redundant codes.\",\n \"The invention has the following advantageous effects: a lookup table f(α j ) consisting of 2m exponents of the primitive field element α is established in the finite field GF (2 m ) to calculate the coefficients of the generator polynomial G(x) and the coefficients of the remainder polynomial R(x) obtained by dividing the code word polynomial Q(x) by the generator polynomial G(x), and the number of data in the lookup table f(α j ) is greatly reduced, thus saving a great deal of system memory and improving the flexibility and convenience in applying the RS error correction algorithm.\"\n ],\n [\n \"CROSS REFERENCE TO RELATED APPLICATIONS The present application is a Continuation Application of PCT Application No.\",\n \"PCT/CN2016/091012 filed on Jul.\",\n \"22, 2016, which claims the benefit of Chinese Patent Application No.\",\n \"201510461188.4 filed on Jul.\",\n \"31, 2015.All the above are hereby incorporated by reference.\",\n \"FIELD OF THE INVENTION The present invention relates to the technical field of error correction codes, and in particular to a Reed-Solomon (RS) error correction decoding method.\",\n \"BACKGROUND OF THE INVENTION In a communication system, it is necessary to artificially add redundant codes to the data stream according to certain rules before information is sent so that a receiving terminal can detect and correct error codes.\",\n \"RS error correction code is currently one of the most effective and widely used error control encoding measures.\",\n \"RS codes can be used to correct random errors, and are also suitable for correcting burst errors, and have been widely used in areas such as satellite communications, digital television transmission or the like.\",\n \"(c, k, 2t) are typically used to represent RS codes; where c is the total length of information data and redundant code, k is the length of the information data, 2t is the length of the redundant code, and t is the maximum number of errors that can be corrected, where c=K+2t.\",\n \"The number of elements in the Galois field (GF) in the conventional RS error correction algorithm is related to the number of primitive polynomials.\",\n \"For example, if the order of a primitive polynomials is 8, then the number of elements in the GF is 28, i.e., 256, the elements in the GF are used for a lookup table in the RS error correction calculation process, and the number of elements in the lookup table reaches 256; and if the order of a primitive polynomial is 16, then the number of elements in the GF is 216, i.e., 65536, which occupies more memory space, and therefore the speed of data processing is slow and the application thereof is limited.\",\n \"In addition, if the number of actual error code words exceeds the error correction capacity, a situation that more errors occur as the error correction proceeds may arise.\",\n \"In addition, in conventional RS error correction algorithms, the error codes are not checked after being found and corrected, so the stability and correctness of the system is not high.\",\n \"Chinese invention patent publication No.\",\n \"CN1303763C discloses a method for reducing the complexity of encoding and decoding RS codes.\",\n \"The invention has the following main features: when encoding at a sending terminal, the code element of the RS code is represented by the power of the primitive field element a, and code words of the RS codes are all in the finite field GF (2m), and all non-zero elements in the finite field GF (2m) are integer powers of the primitive field element α.\",\n \"In coding and decoding, for any two elements X and Y in the finite field GF (2m), multiplication of X and Y equals to addition of the corresponding two exponents, and the addition and subtraction of X and Y are performed using a lookup table.\",\n \"In this way, the coding and decoding method is improved based on existing RS coding and decoding algorithms, the complicated multiplication operation can be avoided and the coding and decoding speed is improved.\",\n \"However, for the finite field GF (2m), three lookup tables have to be established, i and x′ in each group are stored in two long lookup tables, power [ ] and index [ ], and there is a further lookup table f(s), where s is selected from all the integers ranging from 0 to 2m−1, with a total number of 2m.\",\n \"While the calculation speed is fast, the data memory occupied is relatively large, and after the RS error codes are corrected using the redundant codes, no valid data are used for checking, resulting in low security and stability.\",\n \"SUMMARY OF THE INVENTION The technical problem to be addressed by the present invention is to provide a RS error correction decoding method which occupies less memory.\",\n \"In order to address the above technical problem, the invention provides the following technical solutions: A RS error correction decoding method, in which, when encoding at a sending terminal, code words of information data are represented by Kl, code words of redundant codes are represented by T, the order of primitive polynomial P(x) is m, a generator polynomial in GF(2m) is G(x), and an error correction code is represented by (c, k, t), wherein c is the total length of the information data and the redundant code, k is the length of the information data, and t is the length of the redundant code, then the code word polynomial Q(x) can be represented as Q ( x ) = ∑ l = t t + k - 1 K l · x l + ∑ n = 0 t - 1 T n · x n ; root of the m-order primitive polynomial P(x) is primitive field element in GF (2m), and the primitive field element is represented by α, thus the generator polynomial G(x) can be represented as G ( x ) = ∏ t = 1 t ( x - α i ) ; a lookup table f(αj) is established for different power exponents of α, wherein the value of j is selected from all the integers ranging from 0 to 2m−1, with a total number of 2m; the generator polynomial G(x) is expanded to obtain a polynomial with respect to x, wherein the coefficients of the generator polynomial G(x) are the addition or subtraction of the power exponents of α; numerical values of the different power exponents of α are found out through the lookup table f(αj) and the coefficients of the generator polynomial G(x) are calculated; it is assumed that the code words T of the redundant codes are all 0, then a code word polynomial Q ( x ) = ∑ l = t t + k - 1 K l · x l is obtained; the code word polynomial Q(x) is divided by the generator polynomial G(x) to obtain a remainder polynomial R ( x ) = ∑ i = 0 2 s T i · x i ; the coefficients Ti of R(x) are the addition or subtraction of the power exponents of α; numerical values of the power exponents of α are found out through the lookup table f(αj), and the coefficients of the remainder polynomial R(x) are calculated, namely, the code words Tn of the redundant codes.\",\n \"The invention has the following advantageous effects: a lookup table f(αj) consisting of 2m exponents of the primitive field element α is established in the finite field GF (2m) to calculate the coefficients of the generator polynomial G(x) and the coefficients of the remainder polynomial R(x) obtained by dividing the code word polynomial Q(x) by the generator polynomial G(x), and the number of data in the lookup table f(αj) is greatly reduced, thus saving a great deal of system memory and improving the flexibility and convenience in applying the RS error correction algorithm.\",\n \"BRIEF DESCRIPTION OF THE ACCOMPANYING DRAWINGS FIG.\",\n \"1 is a flowchart of performing RS encoding by a sending terminal according to a first embodiment of the present invention; and FIG.\",\n \"2 is a flowchart of RS encoding and error correction according to the first embodiment of the present invention.\",\n \"DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The disclosure, objects and effects of the present invention will be described in detail below with reference to the embodiments and accompanying drawings.\",\n \"The critical concept of the present invention is to establish a lookup table f(αj) for different power exponents of α for a m-order primitive polynomial P(x), where j is selected from all the integers ranging from 0 to 2m−1, with a total number of 2m, for the calculation of coefficients of a generator polynomial G(x) and coefficients of a remainder polynomial R(x) obtained by dividing a code word polynomial Q(x) by the generator polynomial G(x), thus greatly saving the system memory; and a redundant code is additionally taken during encoding, for checking the data obtained by error correction decoding so as to improve system correctness and stability.\",\n \"The technical term involved in the present invention is explained in Table 1: TABLE 1 Technical term Interpretation polynomial A number is represented by a sum of a group of bases (1, representation α, α2, .\",\n \".\",\n \".\",\n \", αn−1), and the group of bases are referred to as standard bases Referring to FIG.\",\n \"1 and FIG.\",\n \"2, a specific embodiment of the present invention is described as follows.\",\n \"A RS error correction decoding method is provided, in which, when encoding at a sending terminal, code words of information data are represented by Kl, code words of redundant codes are represented by Tn, the order of primitive polynomial P(x) is m, a generator polynomial in GF(2m) is G(x), and an error correction code is represented by (c, k, t), wherein c is the total length of the information data and the redundant code, k is the length of the information data, and t is the length of the redundant code, then the code word polynomial Q(x) can be represented as Q ( x ) = ∑ l = t t + k - 1 K l · x l + ∑ n = 0 t - 1 T n · x n ; root of the m-order primitive polynomial P(x) is primitive field element in GF (2m), and the primitive field element is represented by α, thus the generator polynomial G(x) can be represented as G ( x ) = ∏ i = 1 t ( x - a i ) ; a lookup table f(αj) is established for different power exponents of α, wherein the value of j is selected from all the integers ranging from 0 to 2m−1, with a total number of 2m; the generator polynomial G(x) is expanded to obtain a polynomial with respect to x, wherein the coefficients of the generator polynomial G(x) are the addition or subtraction of the power exponents of α; numerical values of the different power exponents of α are found out through the lookup table f(αj) and the coefficients of the generator polynomial G(x) are calculated; it is assumed that the code words Tn of the redundant codes are all 0, then a code word polynomial Q ( x ) = ∑ l = t t + k - 1 K l · x l is obtained; the code word polynomial Q(x) is divided by the generator polynomial G(x) to obtain a remainder polynomial R ( x ) = ∑ i = 0 2 s T i · x i ; the coefficients Ti of R(x) are the addition or subtraction of the power exponents of α; numerical values of the power exponents of α are found out through the lookup table f(αj), and the coefficients of the remainder polynomial R(x) are calculated, namely, the code word Tn of the redundant codes.\",\n \"Further, the error correction decoding process is described as follows: it is assumed that s is the maximum number of error correction bits of a receiving terminal, let t=2s+1; the code word polynomial Q(x) is divided by the generator polynomial G(x) to obtain the remainder polynomial R(x), R ( x ) = ∑ i = 0 2 s T i · x i ; the coefficients of the remainder polynomial R(x) are calculated, thus obtaining the code words Tn of 2s+1 redundant codes, n=1, 2, .\",\n \".\",\n \".\",\n \", 2s+1; the sending terminal sends information data and 2s+1 redundant codes to the receiving terminal; the receiving terminal receives the information data and 2s+1 redundant codes; the receiving terminal obtains the code word polynomial Q(x) by coding according to the received information data and 2s+1 redundant codes, and the code word polynomial Q(x) is represented as Q ( x ) = ∑ l = 2 s + 1 2 s + k K l · x l + ∑ n = 0 2 s T n · x n ; the receiving terminal calculates 2s+1 correctors Si, where Si=Q(αi), i=1, 2, .\",\n \".\",\n \".\",\n \", 2s+1; a location and a correction value of error information code are calculated using correctors Sito S2s if not all of the correctors S, are equal to 0; the correction value is added to the code word at the location of the error information code received by the receiving terminal to obtain an error-corrected code word; the value of the error-corrected code word is assigned to the code word at the location of the error information code; S2s+1=Q(α2s+1) is recalculated, and if S2s+1=0, the error correction is successful, and if S2s+1≠0, received information code error is output and the error correction capacity is insufficient for this.\",\n \"As can be seen from the above description, 2s+1 redundant codes are obtained when the 0th power of x is taken in calculating the redundant codes, and after the error correction codes are calculated using the 1st to the 2sth redundant codes, the (2s+1)th redundant code is used to check whether the error-corrected code word polynomial is correct.\",\n \"In this way, the correctness of the error correction operation is effectively ensured, and the stability of system operation is improved.\",\n \"Further, in the process of obtaining the remainder polynomial R(x) by dividing the code word polynomial Q(x) by the generator polynomial G(x), multiplication of the coefficients of x will be performed, and the multiplication is converted into addition in operation as follows.\",\n \"the coefficients of x are represented by a polynomial representation; the coefficients represented by the polynomial representation are multiplied and expanded to obtain addition of different power exponents of α; the numerical values of the different power exponents of α are found out by looking up the lookup table f(αj) so as to solve the addition.\",\n \"Further, the specific process of calculating the location of the error information code using the correctors S1 to S2s is described as follows: a calculation is performed based on the correctors to obtain an equation taking the location of the error information code as a root; the root of the equation is represented by a polynomial representation, with standard bases being different power exponents of α and coefficients being values of Xi, where i=0, 1, .\",\n \".\",\n \".\",\n \", m; the coefficients of the equation are represented by a polynomial representation, with standard bases being different power exponents of α; the root and coefficients represented by the polynomial representations are brought into the polynomial of the equation; let the coefficient of each term of the polynomial be zero, thus obtaining a non-homogeneous linear equations set for xi; the non-homogeneous linear equation set is solved to obtain the value of xi; the value of xi is brought into the root represented by the polynomial representation to calculate the root of the equation and obtain the location of the error information code; the location in the code word polynomial Q(x) corresponding to the location of the error information code is looked for.\",\n \"Further, looking for the location in the code word polynomial Q(x) corresponding to the location of the error information code is specifically as follows: a numerical value that is the same as the value of the error information code is looked for in the lookup table f(αj), and the coefficient at the location where the exponent value of x in the polynomial Q(x) is equal to the exponent value of α corresponding to the numerical value is the location in the code word polynomial Q(x) corresponding to the error information code; if the numerical value that is the same as the value of the error information code is not found in the lookup table f(αj), the following method is used to find out the location of the error information code, specifically: in step S1, take p=2*m−1=31, v=α2m−1; in step S2, let p=p+1; in step S3, if the highest data bit of v is 1, v is firstly shifted leftward by 1 bit, and then v=v+v0, where v0 is the numerical value obtained by bringing x=α into the primitive polynomial P(x) except for the term of the highest power of x; if the highest data bit of v is 0, v is shifted leftward by 1 bit; in step S4, the v obtained in step S3 is compared with the error information code to see if they are equal: if the v is equal to the error information code, the coefficient corresponding to the pth power of x in the code word polynomial Q (x) is the location of the error information code; and If the v is not equal to the error information code, then turn to step S2 to continue the process.\",\n \"Further, using the correctors S1 to S2s to calculate the correction value is specifically as follows: a equation set consisting of the location of the error information code and the correction value is obtained, where the error information code is the root of the equation set, and the correction value is an unknown number of the equation set; the correction value of the equation set is represented by the polynomial representation, with standard bases being different power exponents of α, and coefficients being values of xi, i=0, 1, .\",\n \".\",\n \".\",\n \", m; the location of the error information code of the equation set is represented by the polynomial representation, with standard bases being different power exponents of α; the correction value and coefficients represented by the polynomial representation are brought into the polynomial of the equation set; let the coefficient of each term of the polynomial be zero, thus obtaining a non-homogeneous linear equation set for xi; the non-homogeneous linear equation set is solved to obtain the value of xi; the value of xi is brought into the correction value represented by the polynomial representation so as to calculate the root of the equation set and obtain the correction value.\",\n \"It can be seen from the above description that in the process of error correction decoding of RS operation, the coefficients and unknown numbers of polynomials are all represented by the polynomial representation, thus the multiplication operation can be converted into addition operation, and solving of equation or equation set can be converted into solving of the non-homogeneous linear equation set so that the complicated operations are simplified, and the calculation process is simplified.\",\n \"The requirements on hardware are reduced, and the correctness of system operation is improved.\",\n \"If the numerical value that is being looked for is beyond the numerical value range of the lookup table f(αj), the numerical value can be calculated by exponential operation.\",\n \"Since the data beyond the numerical value range of the lookup table f(αj) is less in the process of RS error correction decoding, only 2m data are established in the lookup table f(αj), and the memory consumption is therefore reduced.\",\n \"Referring to FIG.\",\n \"1 and FIG.\",\n \"2, the first embodiment of the present invention is described as follows.\",\n \"A RS error correction decoding method is provided, in which when encoding at a sending terminal, five code words of information data, 0x1234, 0x5678, 0x3245, 0xabcd, 0xef10, are represented by Kl, l=5, and the primitive polynomial is P(x)=x16+x5+x3+x2+1, the order of the primitive polynomial is 16, and for a generator polynomial in the GF(216), k is the length of information data, then, k is 5, t is the length of the redundant code, s is the maximum number of error correction bits by the receiving end and is 2; when taking t=2s+1, then t=5, c is the total length of the information data and the redundant code and is 10, the error correction code is represented by (c, k, t), then (c, k, t) is (10, 5, 5), Tn represents the code words of the redundant codes, n=1, 2, .\",\n \".\",\n \".\",\n \", 5, then the code word polynomial Q(x) can be represented as Q ( x ) = ∑ l = t t + k - 1 K l · x l + ∑ n = 0 t - 1 T n · x n ; a root of the 16-order primitive polynomial P(x) is a primitive field element in GF (216), and the primitive field element is represented by α, then the generator polynomial G(x) can be represented as G ( x ) = ∏ i = 1 5 ( x - α i ) ; a lookup table f(αj) for different power exponents of α is established, where the value of j is selected from all the integers ranging from 0 to 31, with a total number of 2m, specifically: {1,2,4,8,0x10,0x20,0x40,0x80,0x100,0x200,0x400,0x800,0x1000,0x2000, 0x4000,0x8000,0x2d,0x5a,0xb4,0x168.0x2d0,0x5a0,0xb40,0x1680,0x2d00, 0x5a00,0xb400,0x682d,0xd05a,0xa099,0x411f,0x8233}; the generator polynomial G(x) is expanded to obtain a polynomial with respect to x, where the coefficients of the generator polynomial G(x) are addition or subtraction of the power exponents of α, specifically: G ( x ) = ∏ i = 1 5 ( x - α i ) = ( x - α ) ( x - α 2 ) ( x - α 3 ) ( x - α 4 ) ( x - α 5 ) = x 5 + ( α + α 2 + α 3 + α 4 + α 5 ) x 4 + ( α 3 + α 4 + α 8 + α 9 ) x 3 + ( α 7 + α 8 + α 11 + α 12 ) x 2 + ( α 10 + α 11 + α 12 + α 13 + α 14 ) x + α 15 ; numerical values of the different power exponents of α are found out through the lookup table f(αj) and the coefficients of the generator polynomial G(x) are calculated, specifically: G(x)=x5+0x3e*x4+0x318*x3+0x18c0*x2+0x7c00*x+0x8000; it is assumed that each code word Tn of the redundant codes is 0, then the code word polynomial Q ( x ) = ∑ l = t t + k - 1 K l · x l is obtained, specifically: Q(x)=0x1234*x9+0x5678*x8+0x3245*x7+0xabcd*x6+0xef10*x5+0*x4+0*x3+0*x2+0* x1+0*x0; the code word polynomial Q(x) is divided by the generator polynomial G(x) to obtain a remainder polynomial R ( x ) = ∑ i = 0 2 s T i · x i .\",\n \"In calculating the remainder polynomial R(x), multiplication of coefficients of x will be performed, and the multiplication operation is converted into addition operation, specifically: 0x1234*0x18c0 is taken as an example; the coefficients of x in the code word polynomial Q(x) and the generator polynomial G(x) are represented by a polynomial representation, specifically: 0x1234=0*α15+0*α14+0*α13+1*α12+0*α11+0*α10+1*α9+0*α8+0*α7+0*α6+1*α5+1*α4+0*α3+1*α2+0*α1+0*α0=α12+α9+α5+α4+α2; 0x18c0=0*α15+0*α14+0*α13+1*α12+1*α11+0*α10+0*α9+0*α8+1*α7+1*α6+0*α5+0*α4+0*α3+0*α2+0*α1+0*α0=α12+α11+α7+α6; the coefficients represented by the polynomial representation are multiplied and expanded to obtain addition of different power exponents of α: 0 x 1234 * 0 x 18 c 0 = ( α 12 + α 9 + α 5 + α 4 + α 2 ) * ( α 12 + α 11 + α 7 + α 6 ) = α 24 + α 21 + α 17 + α 16 + α 14 + α 23 + α 20 + α 16 + α 15 + α 13 + α 19 + α 16 + α 12 + α 11 + α 9 + α 18 + α 15 + α 11 + α 10 + α 8 = α 24 + α 23 + α 21 + α 20 + α 19 + α 18 + α 17 + α 16 + α 14 + α 13 + α 12 + α 10 + α 9 + α 8 = 0 x 2 d 00 + 0 x 1680 + 0 x 5 a 0 + 0 x 2 d 0 + 0 x 168 + 0 x b 4 + 0 x 5 a + 0 x 2 d + 0 x 4000 + 0 x 2000 + 0 x 1000 + 0 x 400 + 0 x 200 + 0 x 100 = 0 x 4 a 5 b ; the numerical values of the power exponents of α are found out through the lookup table f(αj), and the coefficients of the remainder polynomial R(x), i.e., the code words of the redundant codes Tn, n=1, 2, .\",\n \".\",\n \".\",\n \", 5, are calculated; the remainder polynomial R(x) is obtained: |R(x)=0x15d4*x4+0x2606*x3+0x3587*x2+0x417e*x1+0x121c*x0; code words of the five redundant codes are 0x15d4, 0x2606, 0x3587, 0x417e, 0x121c; the sending terminal sends five information data and five redundant codes 0x1234, 0x5678, 0x3245, 0xabcd, 0xef10, 0x15d4, 0x2606, 0x3587, 0x417e, 0x121c to the receiving terminal.\",\n \"It is assumed that the third information data and the third redundant code received by the receiving terminal are in error, then the information data and the redundant codes received by the receiving terminal are 0x1234, 0x5678, 0xe305, 0xabcd, 0xef10, 0x15d4, 0x2606, 0xa513, 0x417e , 0x121c.\",\n \"The code word polynomial Q(x) obtained by the receiving terminal according to the received information data and redundant codes is: Q(x)=0x1234*x9+0x5678*x8+0xe305*x7+0xabcd*x6+0xef10* x5+0x15d4*x4+0x2606*x3+0x513*x2+0x417e*x1+0x121c*x0.The receiving terminal calculates five correctors Si, where Si=Q(αi), i=1, 2, .\",\n \".\",\n \".\",\n \", 5, specifically, S1=Q(α1)=0xed82; S2=Q(α2)=0xc556; S3=Q(α3)=0x879a; S4=Q(α4)=0x4eb7; S5=Q(α5)=0x7cb9; if not all of the correctors Si are equal to 0, then the location of the error information code and the correction value are calculated using the correctors S1 to S2s; specifically, calculation is performed according to the correctors to obtain the equation SS2·x2+SS1·x+SS0=0, and the root of the equation is the location of the error code.\",\n \"Let s1=(s1 s2), s2=(s2 s3), s3=(s3 s4), then SS2=|S1T S2T|=S2*S2+S1*S3=0x219f; SS1=|S1T S3T|=S4*S1+S3*S2=0x4b2c; SS0=|S2T S1T|=S4*S2+S3*S3=0x3537; then the equation is 0x219f·x2+0x4b2c·|x+0x3537=0, and the solution to this equation is as follows: the roots of the equation are represented by the polynomial representation, that is, x and x2 are represented by the polynomial representation as: x=x15α15+x14α14+x13α13+x12α12+x11α11+x10α10+x9α9+x8α8+x7α7+x6α6+x5α5+x|4α4x3α3+x2α2+x1α1x0α0; x2=x15α30+x14α28+x13α26+x12α24+x11α22+x10α20+x9α18+x8α16+x7α14+x6α12+x5α10+x4α8+x3α6+x2α4+x1α2+x0α0; where xi can only take 0 or 1, i=1, 2, .\",\n \".\",\n \".\",\n \", 15; the values of x and x2 are brought into the left of the equation to obtain 0x219f*x2+0x4b2c*x+0x3537=0xe006x15+0xe5c6x14+0x1799x13+0x1292x12+0x 2f1bx12+0x1e19x10+0x2d6cx9+0xbe3dx8+0x3537x7+0x6d1fx6+0 xoeabx5+0x28f9x4+0x3f92x3+0x3527x2+0x1024x1+0x6ab3x0; the exponents of α corresponding to the coefficients of xi are looked for in the lookup table f(αj), and the left side of the equation is converted into the expression of the exponents of α and xi, specifically: 0x219f*x2+0x4b2c*x+0x3537 =0xe006x15+0xe5c6x14+0x1799x13+0x1292x12+0x2f1bx11 +0x1e19x10+0x2d6cx9+0xbe3dx8+0x3537x7+0x6d1fx6 +0xoeabx5+0x28f9x4+0x3f92x3+0x3527x2+0x1024x1+0x6ab3x0 =(x0+x2+x4+x5+x6+x7+x8+x10+x11+x13+1)*α0 +(x0+x2+x3+x5+x6+x7+x11+x12+x14+x15+1)*α1 +(x1+x2+x6+x7+x8+x9+x14+x15+1)*α2 +(x4+x5+x6+x8+x9+x10+x11+x13+0)*α3 +(x0+x2+x3+x4+x6+x7+x8+x10+x11+x12+x13+1)*α4 +(x0+x1+x2+x4+x5+x7+x8+x9+1)*α5 +(x4+x9+x14+0)*α6 +(x0+x3+x4+x5+x12+x13+x14+0)*α7 +(x2+x3+x7+x9+x11+x13+x14+1)*α8 +(x0+x3+x5+x8+x10+x11+x12+x13+0)*α9 +(x2+x3+x5+x7+x8+x9+x10+x11+x13+x14+1)*α10 +(x0+x3+x4+x5+x8+x9+x10+x11+0)*α11 +(x1+x2+x3+x7+x8+x10+x12+x13+1)*α12 +(x0+x2+x3+x4+x6+x7+x8+x9+x11+x14+x15+1)*α13 +(x0+x6+x14+x15+0)*α14 +(x8+x14+x15+0)*α15; let all the above coefficients of αi be equal to 0, thus obtaining 16 equations: x0+x2+x4+x5+x6+x7+x8+x10+x11+x13=1; x0+x2+x3+x5+x6+x7+x11+x12+x14+x15=1; x1+x2+x6+x7+x8+x9+x14+x15=1; x4+x5+x6+x8+x9+x10+x11+x13=0; x0+x2+x3+x4+x6+x7+x8+x10+x11+x12+x13=1; x0+x1+x2+x4+x5+x7+x8+x9=1; x4+x9+x14=0; x0+x3+x4+x5+x12+x13+x14=0; x2+x3+x7+x9+x11+x13+x14=1; x0+x3+x5+x8+x10+x11+x12+x13=0; x2+x3+x5+x7+x8+x9+x10+x11+x13+x14=1; x0+x3+x4+x5+x8+x9+x10+x11=0; x1+x2+x3+x7+x8+x10+x12+x131; x0+x2+x3+x4+x6+x7+x8+x9+x11+x14+x151; x0+x6+x14+x15=0; x8+x14+x15=0; the above 16 equations are converted into a non-homogeneous linear equation set for xi, and a matrix consisting of the coefficients of xi′ and numerical values of constant terms is obtained: [ 1 0 1 0 1 1 1 1 1 0 1 1 0 1 0 0 1 1 0 1 1 0 1 1 1 0 0 0 1 1 0 1 1 1 0 1 1 0 0 0 1 1 1 1 0 0 0 0 1 1 1 0 0 0 0 1 1 1 0 1 1 1 1 0 1 0 0 0 1 0 1 1 1 0 1 1 1 0 1 1 1 1 0 0 1 1 1 1 0 1 1 0 1 1 1 0 0 0 0 0 0 1 0 0 0 0 1 0 0 0 0 1 0 0 0 0 1 0 0 1 0 0 1 1 1 0 0 0 0 0 0 1 1 1 0 0 0 0 1 1 0 0 0 1 0 1 0 1 0 1 1 0 1 1 0 0 1 0 1 0 0 1 0 1 1 1 1 0 0 0 0 0 1 1 0 1 0 1 1 1 1 1 0 1 1 0 1 1 0 0 1 1 1 0 0 1 1 1 1 0 0 0 0 0 0 1 1 1 0 0 0 1 1 0 1 0 1 1 0 0 1 1 0 1 1 1 0 1 1 1 1 0 1 0 0 1 1 1 1 0 0 0 0 0 1 0 0 0 0 0 0 0 1 1 0 0 0 0 0 0 0 0 0 1 0 0 0 0 0 1 1 0 ] ; the above non-homogeneous linear equation set is solved to obtain x1=0x0004, x2=0x0080; in the lookup table f(αj), the locations corresponding to x1 and x2 are the second power of α and the seventh power of α respectively; thus, the locations of the error information codes in the code word polynomial Q(x) are the coefficients corresponding to the second power and the seventh power of x, namely, 0xa513 and 0xe305.If no values that are the same as the values of x1 and x2 are found in the lookup table f(αj), the following method is used to find out the location of the error code, specifically: in step S1, take p=2*m−1=31, v=α2m−1=0x823e; in step S2, let p=p+1; in step S3, if the highest data bit of v is 1, v is firstly shifted leftward by 1 bit, and then v=v+0x1d, where 0x1d is the numerical value obtained by bringing x=α into x5+x3+x2+1 in the primitive polynomial P(x)=x16+x5+x3+x2+1; if the highest data bit of v is 0, v is shifted leftward by 1 bit; in step S4, the v obtained in step S3 is compared with x1 or x2 to see if they are equal: if the v is equal to x1 or x2, the coefficient corresponding to the pth power of x in the code word polynomial Q (x) is the location of the error information code; and If the v is not equal to x1 or x2, then turn to step S2 to continue the process.\",\n \"The error value is calculated according to the following two equations: S1=e1·x1+e2·x2=0xed82; S2=e1·x12+e2·x22=0xc556; values of x1 and x2 are brought into the above two equations to yield e1=0x9094 and e2=0xd140, specifically: S1*x1−S2 is calculated to yield (x1·x2−x22)·e2=0xed82=0xc556; e2 is represented in polynomial representation as: e2=x15α15+x14α14+x13α13+x12α12+x11α11+x10α10+x9α9+x8α8+x7α7+x6α6+x5α5+x4α4+x3α3+x2α2+x1α1+x0α0; where xi can only take 0 or 1, i=1, 2, .\",\n \".\",\n \".\",\n \", 15; the value of e2 is brought into (x1·x2−x22)·e2=0xed82−0xc556 to obtain the non-homogeneous linear equation set and yield e2=0xd140; and in a similar principle, yield e1=0x9094; the correction value is added to the code word at the location of the error information code received by the receiving terminal to obtain error-corrected code word, specifically: in the error-corrected code word polynomial Q(x), the coefficient of the second power of x is: 0xa513+0x9094=0x3587, and the coefficient of the seventh power of x is: 0xe305+0xd140=0x3245; the value of the error-corrected code word is assigned to the code word at the location of the error information code so as to obtain the error-corrected code word polynomial Q(x) as follows: Q(x)=0x1234*x9+0x5678*x8+0x3245*x7+0xabcd*x6+0xef10*x5+0x15d4*x4+0x2606*x3+0x3587*x2+0x417e*x1+0x121c*x0; S5=Q(α5) is recalculated, and if S5=0 is yielded, the error correction is successful.\",\n \"To sum up, in the RS error correction decoding method according to the present invention, a lookup table f(αj) for different power exponents of α is established, where j is selected from all the integers ranging from 0 to 2m−1, and with a total number of 2m, for the calculation of the coefficients of the generator polynomial G(x) and the coefficients of the remainder polynomial R(x) obtained by dividing the code word polynomial Q(x) by the generator polynomial G(x), thus greatly saving system memory; one additional redundant code is taken in encoding, for the purpose of checking the data obtained after the error correction decoding, thereby improving correctness and stability of the system.\"\n ]\n]"},"source":{"kind":"string","value":"Patent_15871939"}}},{"rowIdx":4493961,"cells":{"text":{"kind":"list like","value":[["Three Dimensional Structural Frames and Enclosures","Three dimensional structural frames and enclosures and related methods are disclosed herein.","In an example embodiment, an enclosure includes a plurality of three dimensional structural frames and opposing wall portions interconnected by the plurality of three dimensional structural frames, where the wall portions include a plurality of uniform wall sections, where the wall sections include a wall panel portion, a top wall portion, and sidewall portions, where the sidewall portions of the plurality of wall sections are joined to form the wall portions, and where the plurality of three dimensional structural frames are attached to the top wall portions of the wall sections."],["1.An enclosure, comprising: (a) a plurality of three dimensional structural frames, wherein at least one three dimensional structural frame of the plurality of three dimensional structural frames comprises: two three dimensional structural frame members connected at their first ends, wherein each three dimensional structural frame member of the two three dimensional structural frame members comprises: a frame member comprising a variable cross section three dimensional structure comprising the first end, a second end, a first flange, a web, and a second flange, wherein the web extends from the first end to the second end, and wherein the web extends from the first flange to the second flange, a mounting flange at the second end of the variable cross section three dimensional structure that at least partially encloses the second end, wherein the mounting flange comprises through holes for mounting the frame member, and a transverse stiffener positioned within the variable cross section three dimensional structure comprising a rigid support structure rigidly fixed to the first flange, the web, and the second flange of the variable cross section three dimensional structure; and (b) opposing wall portions interconnected by the plurality of three dimensional structural frames, wherein the wall portions comprise a plurality of uniform wall sections, wherein the wall sections each comprise a wall panel portion, a top wall portion that extends from the wall panel portion, and sidewall portions that extend from the wall panel portion, wherein the sidewall portions of the plurality of wall sections are joined to form the wall portions, and wherein the plurality of three dimensional structural frames are attached to the top wall portions of the wall sections.","2.The enclosure of claim 1, wherein the at least one three dimensional structural frame of the plurality of three dimensional structural frames further comprises a connector for a fall protection harness sandwiched between the first ends of the two three dimensional structural frame members, wherein the connector comprises a first surface and a second surface opposite the first surface, wherein a first portion of the first surface contacts the first end of one of the two three dimensional structural frame members, wherein a first portion of the second surface contacts the first end of the other three dimensional structural frame member, and wherein a second portion of the first surface and a second portion of the second surface each extend above each second flange of the two three dimensional structural frame members.","3.The enclosure of claim 1, wherein the wall sections each further comprise a bottom wall portion that extends from the wall panel portion.","4.The enclosure of claim 1, wherein the sidewalls of the plurality of wall sections are connected by a plurality of rivets, wherein the enclosure further comprises a gasket between at least two sidewall portions of the sidewall portions, and wherein the gasket comprises a silicone bead, polyurethane, or structural adhesive.","5.The enclosure of claim 1, further comprising: a roof comprising a plate secured to at least one three dimensional structural frame of the three dimensional structural frames and an overlaying weatherproof membrane, wherein the plate comprises sheet metal, and wherein the overlaying weatherproof membrane is attached to the wall panel portions of the wall sections.","6.The enclosure of claim 1, further comprising a strengthening member connected to at least some three dimensional structural frames of the plurality of three dimensional structural frames; and a lift plate for engaging the ends of the plurality of three dimensional structural frames, wherein the lift plate comprises (a) a planar portion comprising a series of a pattern of mounting holes for receiving hardware for securing the plate to the ends of the plurality of frames, and (b) a connecting portion for engaging a harness that provides upward force to lift the plate and the frames, wherein the connecting portion comprises two reinforcement plates.","7.A method for lifting the enclosure of claim 1, comprising: (a) attaching a plurality of lift plates to at least some second ends of the three dimensional structural frames and at least some of the wall panel sections of the opposing walls, wherein a first lift plate of the plurality of lift plates is secured to two or more frames of the three dimensional structural frames, and wherein a second lift plate of the plurality of lift plates is secured to two or more other frames of the three dimensional structural frames, and wherein the first lift plate is secured to two or more wall panel sections of the opposing walls, and the second lift plate is secured to two or more other wall panel sections of the opposing walls; (b) attaching a harness to the plurality of lift plates; and (c) lifting the enclosure with an upward force to the harness, wherein the first lift plate and the second lift plate each comprises (i) a planar portion comprising a series of a pattern of mounting holes for receiving hardware for securing the plate to the ends of the plurality of frames and the wall panel sections; and (ii) a connecting portion for attaching the harness.","8.An enclosure, comprising: (a) a plurality of three dimensional structural frames, wherein at least one three dimensional structural frame of the plurality of three dimensional structural frames comprises: two three dimensional structural frame members connected at their first ends, wherein each three dimensional structural frame member of the two three dimensional structural frame members comprises: a frame member comprising a three dimensional structure comprising the first end, a second end, a first flange, a web, and a second flange, wherein the first end has a first width, the second end has a second width, and the first and second widths are substantially equal, wherein the web extends from the first end to the second end, and wherein the web extends from the first flange to the second flange, a mounting flange at the second end of the three dimensional structure that at least partially encloses the second end, wherein the mounting flange comprises through holes for mounting the frame member, and a transverse stiffener positioned within the three dimensional structure comprising a rigid support structure rigidly fixed to the first flange, the web, and the second flange of the three dimensional structure; and (b) opposing wall portions interconnected by the plurality of three dimensional structural frames, wherein the wall portions comprise a plurality of uniform wall sections, wherein the wall sections each comprise a wall panel portion, a top wall portion that extends from the wall panel portion, and sidewall portions that extend from the wall panel portion, wherein the sidewall portions of the plurality of wall sections are joined to form the wall portions, and wherein the plurality of three dimensional structural frames are attached to the top wall portions of the wall sections.","9.The enclosure of claim 8, wherein the at least one three dimensional structural frame of the plurality of three dimensional structural frames further comprises a connector for a fall protection harness sandwiched between the first ends of the two three dimensional structural frame members, wherein the connector comprises a first surface and a second surface opposite the first surface, wherein a first portion of the first surface contacts the first end of one of the two three dimensional structural frame members, wherein a first portion of the second surface contacts the first end of the other three dimensional structural frame member, and wherein a second portion of the first surface and a second portion of the second surface each extend above each second flange of the two three dimensional structural frame members.","10.The enclosure of claim 8, wherein the wall sections each further comprise a bottom wall portion that extends from the wall panel portion.","11.The enclosure of claim 8, wherein the sidewalls of the plurality of wall sections are connected by a plurality of rivets, wherein the enclosure further comprises a gasket between at least two sidewall portions of the sidewall portions, and wherein the gasket comprises a silicone bead, polyurethane, or structural adhesive.","12.The enclosure of claim 8, further comprising: a roof comprising a plate secured to at least one three dimensional structural frame of the three dimensional structural frames and an overlaying weatherproof membrane, wherein the plate comprises sheet metal, and wherein the overlaying weatherproof membrane is attached to the wall panel portions of the wall sections.","13.The enclosure of claim 8, further comprising a strengthening member connected to at least some three dimensional structural frames of the plurality of three dimensional structural frames; and a lift plate for engaging the ends of the plurality of three dimensional structural frames, wherein the lift plate comprises (a) a planar portion comprising a series of a pattern of mounting holes for receiving hardware for securing the plate to the ends of the plurality of frames, and (b) a connecting portion for engaging a harness that provides upward force to lift the plate and the frames, wherein the connecting portion comprises two reinforcement plates.","14.A method for lifting the enclosure of claim 8, comprising: (a) attaching a plurality of lift plates to at least some second ends of the three dimensional structural frames and at least some of the wall panel sections of the opposing walls, wherein a first lift plate of the plurality of lift plates is secured to two or more frames of the three dimensional structural frames, and wherein a second lift plate of the plurality of lift plates is secured to two or more other frames of the three dimensional structural frames, and wherein the first lift plate is secured to two or more wall panel sections of the opposing walls, and the second lift plate is secured to two or more other wall panel sections of the opposing walls; (b) attaching a harness to the plurality of lift plates; and (c) lifting the enclosure with an upward force to the harness, wherein the first lift plate and the second lift plate each comprises (i) a planar portion comprising a series of a pattern of mounting holes for receiving hardware for securing the plate to the ends of the plurality of frames and the wall panel sections; and (ii) a connecting portion for attaching the harness.","15.An enclosure, comprising: (a) a plurality of three dimensional structural frames, wherein at least one three dimensional structural frame of the plurality of three dimensional structural frames comprises: a frame member comprising an elongated three dimensional structure having a first side, a second side, a center support portion, a first flange, a web, and a second flange, wherein the first side has a variable cross section from a first end to the center support portion, wherein the second side has a variable cross section from a second end to the center support portion, wherein the web extends from the first end to the second end, and wherein the web extends from the first flange to the second flange, the frame member further comprising mounting flanges at the first end and the second end that at least partially enclose the first end and the second end, wherein the mounting flanges comprise through holes for mounting the frame member, and transverse stiffeners positioned within the three dimensional structure on the first side and the second side comprising a rigid support structure rigidly fixed to the first flange, the web, and the second flange of the three dimensional structure, wherein the transverse stiffeners are welded to the first flange, the web, and the second flange of the elongated three dimensional structure; and (b) opposing wall portions interconnected by the plurality of three dimensional structural frames, wherein the wall portions comprise a plurality of uniform wall sections, wherein the wall sections each comprise a wall panel portion, a top wall portion that extends from the wall panel portion, and sidewall portions that extend from the wall panel portion, wherein the sidewall portions of the plurality of wall sections are joined to form the wall portions, and wherein the plurality of three dimensional structural frames are attached to the top wall portions of the wall sections.","16.The enclosure of claim 15, wherein the at least one three dimensional structural frame of the plurality of three dimensional structural frames further comprises a center support mounted at the center support portion, wherein the center support comprises a connector for a fall protection harness, wherein the connector comprises a first surface and a second surface opposite the first surface, wherein the first surface faces the first end, wherein the second surface faces the second end, such that the first surface and the second surface are each perpendicular to an axis that extends between the first end and the second end, wherein a first portion of the first surface and a first portion of the second surface each contact the second flange, and wherein a second portion of the first surface and a second portion of the second surface each extend above the second flange.","17.The enclosure of claim 15, wherein the wall sections each further comprise a bottom wall portion that extends from the wall panel portion.","18.The enclosure of claim 15, wherein the sidewalls of the plurality of wall sections are connected by a plurality of rivets, wherein the enclosure further comprises a gasket between at least two sidewall portions of the sidewall portions, and wherein the gasket comprises a silicone bead, polyurethane, or structural adhesive.","19.The enclosure of claim 15, further comprising: a roof comprising a plate secured to at least one three dimensional structural frame of the three dimensional structural frames and an overlaying weatherproof membrane, wherein the plate comprises sheet metal, and wherein the overlaying weatherproof membrane is attached to the wall panel portions of the wall sections.","20.The enclosure of claim 15, further comprising a strengthening member connected to at least some three dimensional structural frames of the plurality of three dimensional structural frames; and a lift plate for engaging the ends of the plurality of three dimensional structural frames, wherein the lift plate comprises (a) a planar portion comprising a series of a pattern of mounting holes for receiving hardware for securing the plate to the ends of the plurality of frames, and (b) a connecting portion for engaging a harness that provides upward force to lift the plate and the frames, wherein the connecting portion comprises two reinforcement plates.","21.A method for lifting the enclosure of claim 15, comprising: (a) attaching a plurality of lift plates to at least some second ends of the three dimensional structural frames and at least some of the wall panel sections of the opposing walls, wherein a first lift plate of the plurality of lift plates is secured to two or more frames of the three dimensional structural frames, and wherein a second lift plate of the plurality of lift plates is secured to two or more other frames of the three dimensional structural frames, and wherein the first lift plate is secured to two or more wall panel sections of the opposing walls, and the second lift plate is secured to two or more other wall panel sections of the opposing walls; (b) attaching a harness to the plurality of lift plates; and (c) lifting the enclosure with an upward force to the harness, wherein the first lift plate and the second lift plate each comprises (i) a planar portion comprising a series of a pattern of mounting holes for receiving hardware for securing the plate to the ends of the plurality of frames and the wall panel sections; and (ii) a connecting portion for attaching the harness."],[" BACKGROUND Enclosures may be used to surround equipment located outside of a building in an industrial facility or equipment located inside of a building.","Such enclosures may protect the equipment from a variety of environmental conditions, such as extreme temperatures, humidity, and moisture."],[" SUMMARY In one aspect, a three dimensional structural member is disclosed.","The three dimensional structural member includes a frame member that includes a variable cross section three dimensional structure that includes a first end and a second end; a mounting flange at the second end of the variable cross section three dimensional structure that at least partially encloses the second end, where the mounting flange includes through holes for mounting the frame member; and a transverse stiffener positioned within the variable cross section three dimensional structure that includes a rigid support structure rigidly fixed to a first flange, a web, and a second flange of the variable cross section three dimensional structure.","In another aspect, a three dimensional structural frame member is disclosed, where the variable cross section three dimensional structure is a single piece of sheet metal.","In another aspect, a three dimensional structural frame member is disclosed, where the variable cross section three dimensional structure and the mounting flange include a single piece of sheet metal.","In another aspect, a three dimensional structural frame member is disclosed, where the variable cross section three dimensional structure is an open three dimensional structure.","In another aspect, a three dimensional structural frame member is disclose, where the transverse stiffener is welded to the first flange, the web, and the second flange of the variable cross section three dimensional structure.","In another aspect, a three dimensional structural frame is disclosed.","The three dimensional structural frame includes two three dimensional structural frame members connected at their first ends.","In another aspect, a three dimensional structural frame is disclosed, further including a connector for a fall protection harness between the firsts ends of the two three dimensional structural frame members.","In another aspect, a three dimensional structural frame member is disclosed.","The three dimensional structural frame member includes a frame member that includes a three dimensional structure that includes a first end and a second end, where the first end has a first width, the second end has a second width, and the first and second widths are substantially equal; a mounting flange at the second end of the three dimensional structure that at least partially encloses the second end, where the mounting flange includes through holes for mounting the frame member; and a transverse stiffener positioned within the three dimensional structure that includes a rigid support structure rigidly fixed to a first flange, a web, and a second flange of the three dimensional structure.","In another aspect, a three dimensional structural frame is disclosed, where the three dimensional structure is a single piece of sheet metal.","In another aspect, a three dimensional structural frame is disclosed, where the three dimensional structure and the mounting flange include a single piece of sheet metal.","In another aspect, a three dimensional structural frame is disclosed, where the three dimensional structure is an open three dimensional structure.","In another aspect, a three dimensional structural frame is disclosed, where the transverse stiffener is welded to the first flange, the web, and the second flange of the three dimensional structure.","In another aspect, a three dimensional structural frame is disclosed.","The three dimensional structural frame includes two three dimensional structural frames connected at their first ends.","In another aspect, a three dimensional structural frame is disclosed, further including a connector for a fall protection harness between the firsts ends of the two three dimensional structural frame members.","In another aspect, a three dimensional structural frame is disclosed.","The three dimensional structural frame includes a frame member that includes an elongated three dimensional structure having a first side, a second side, and a center support portion, where the first side has a variable cross section from a first end to the center support portion, and where the second side has a variable cross section from a second end to the center support portion, the frame member further includes mounting flanges at the first end and the second end that at least partially enclose the first end and the second end, where the mounting flanges include through holes for mounting the frame member; a center support mounted at the center support portion; and transverse stiffeners positioned within the three dimensional structure on the first side and the second side that includes a rigid support structure rigidly fixed to a first flange, a web, and a second flange of the three dimensional structure.","In another aspect, a three dimensional structural frame is disclosed, where the frame member is a single piece of sheet metal.","In another aspect, a three dimensional structural frame is disclosed, where the center support includes a connector for a fall protection harness.","In another aspect, a three dimensional structural frame is disclosed, where the transverse stiffeners are welded to the first flange, the web, and the second flange of the three dimensional structure.","In another aspect, an enclosure is disclosed.","The enclosure includes a plurality of three dimensional structural frames; and opposing wall portions interconnected by the plurality of three dimensional structural frames, where the wall portions include a plurality of uniform wall sections, where the wall sections include a wall panel portion, a top wall portion, and sidewall portions, where the sidewall portions of the plurality of wall sections are joined to form the wall portions, where the plurality of three dimensional structural frames are attached to the top wall portions of the wall sections.","In another aspect, an enclosure is disclosed, where the ends of the three dimensional structural frames overlap and are simultaneously attached to two wall sections.","In another aspect, an enclosure is disclosed, where the wall sections include a single piece of formed sheet metal.","In another aspect, an enclosure is disclosed, further including a plurality of support members, where the support members extend between the opposing wall portions.","In another aspect, an enclosure is disclosed, where the wall sections include a bottom wall portion.","In another aspect, an enclosure is disclosed, where the sidewalls of the plurality of wall sections are connected by a plurality of rivets.","In another aspect, an enclosure is disclosed, further including a gasket between the sidewall portions.","In another aspect, an enclosure is disclosed, where the gasket includes a silicone bead, polyurethane, or structural adhesive.","In another aspect, an enclosure is disclosed, further including a roof that includes a plate secured to the three dimensional structural frames.","In another aspect, an enclosure is disclosed, where the plate includes sheet metal.","In another aspect, an enclosure is disclosed, where the plate includes perforated sheet metal.","In another aspect, an enclosure is disclosed, where the roof further includes a weatherproof membrane overlaying the plate and attached to the wall panel portions of the wall sections.","In another aspect, an enclosure is disclosed, further including a first support member connected to a first group of wall sections, and a second support member connected to a second group of wall sections.","In another aspect, an enclosure disclosed, further including a strengthening member connected to the plurality of three dimensional structural frames.","In another aspect, a lift plate for engaging the ends of a plurality of three dimensional structural frames is disclosed.","The lift plate includes a planar portion that includes a series of a pattern of mounting holes for receiving hardware for securing the plate to the ends of the plurality of frames; and a connecting portion for engaging a harness that provides upward force to lift the plate and the frames.","In another aspect, a lift plate is disclosed, where the connecting portion includes a reinforcement plate.","In another aspect, a lift plate is disclosed, where the connecting portion includes two reinforcement plates.","In another aspect, a liftable enclosure is disclosed.","The liftable enclosure includes a plurality of the three dimensional structural frames; and at least two lift plates that include a planar portion that includes a series of a pattern of mounting holes for receiving hardware for securing the plate to the ends of the plurality of frames and a connecting portion for engaging a harness that provides an upward force to lift the plate and the frames.","In another aspect, a liftable enclosure is disclosed, further including opposing walls interconnected by the plurality of three dimensional structural frames, where the walls include a plurality of uniform wall sections, where the wall sections include a wall panel portion, a top wall portion, and sidewall portions, where the sidewall portions of the plurality of wall sections are connected to form at least a portion of a wall of the enclosure, where the plurality of three dimensional structural frames are attached to the top wall portions of the wall sections.","In another aspect, a liftable enclosure is disclosed, where the lift plates are further connected to the wall panel portions of the wall sections.","In another aspect, a method for building a structure is disclosed.","The method includes fabricating opposing walls of the structure by attaching sidewall portions of a plurality of wall sections comprising a wall panel portion, a top wall portion, and sidewall portions, where the sidewall portions of the plurality of wall sections; and attaching a plurality of three dimensional structural frames to the top walls portions of the wall sections of the opposing walls.","In another aspect, a method is disclosed, where the opposing walls are fabricated while the sidewall portions are substantially horizontal.","In another aspect, a method is disclosed, where the opposing walls are uprighted by attaching a lift plate to a top end of a plurality of wall sections and lifting the top end.","In another aspect, a method for lifting an enclosure is disclosed.","The method includes attaching a plurality of lift plates to the a plurality of the ends of the three dimensional structural frames and the wall panel sections of the opposing walls; attaching a harness to the plurality of lift plates; and lifting the structure with an upward force to the harness, where the lift plates include a planar portion that includes a series of a pattern of mounting holes for receiving hardware for securing the plate to the ends of the plurality of frames and the wall panel sections, and a connecting portion for attaching the harness."],["CROSS REFERENCE TO RELATED APPLICATIONS The present application is a continuation of U.S. application Ser.","No.","14/818,046, filed Aug. 4, 2015, entitled “Three Dimensional Structural Frames and Enclosures,” which claims priority to U.S.","Provisional Application No.","62/160,556, filed May 12, 2015, entitled “Three Dimensional Structural Frames and Enclosures.” The entire disclosure contents of U.S. application Ser.","No.","14/818,046 and U.S.","Provisional Application No.","62/160,556 are herewith incorporated by reference into the present application.","BACKGROUND Enclosures may be used to surround equipment located outside of a building in an industrial facility or equipment located inside of a building.","Such enclosures may protect the equipment from a variety of environmental conditions, such as extreme temperatures, humidity, and moisture.","SUMMARY In one aspect, a three dimensional structural member is disclosed.","The three dimensional structural member includes a frame member that includes a variable cross section three dimensional structure that includes a first end and a second end; a mounting flange at the second end of the variable cross section three dimensional structure that at least partially encloses the second end, where the mounting flange includes through holes for mounting the frame member; and a transverse stiffener positioned within the variable cross section three dimensional structure that includes a rigid support structure rigidly fixed to a first flange, a web, and a second flange of the variable cross section three dimensional structure.","In another aspect, a three dimensional structural frame member is disclosed, where the variable cross section three dimensional structure is a single piece of sheet metal.","In another aspect, a three dimensional structural frame member is disclosed, where the variable cross section three dimensional structure and the mounting flange include a single piece of sheet metal.","In another aspect, a three dimensional structural frame member is disclosed, where the variable cross section three dimensional structure is an open three dimensional structure.","In another aspect, a three dimensional structural frame member is disclose, where the transverse stiffener is welded to the first flange, the web, and the second flange of the variable cross section three dimensional structure.","In another aspect, a three dimensional structural frame is disclosed.","The three dimensional structural frame includes two three dimensional structural frame members connected at their first ends.","In another aspect, a three dimensional structural frame is disclosed, further including a connector for a fall protection harness between the firsts ends of the two three dimensional structural frame members.","In another aspect, a three dimensional structural frame member is disclosed.","The three dimensional structural frame member includes a frame member that includes a three dimensional structure that includes a first end and a second end, where the first end has a first width, the second end has a second width, and the first and second widths are substantially equal; a mounting flange at the second end of the three dimensional structure that at least partially encloses the second end, where the mounting flange includes through holes for mounting the frame member; and a transverse stiffener positioned within the three dimensional structure that includes a rigid support structure rigidly fixed to a first flange, a web, and a second flange of the three dimensional structure.","In another aspect, a three dimensional structural frame is disclosed, where the three dimensional structure is a single piece of sheet metal.","In another aspect, a three dimensional structural frame is disclosed, where the three dimensional structure and the mounting flange include a single piece of sheet metal.","In another aspect, a three dimensional structural frame is disclosed, where the three dimensional structure is an open three dimensional structure.","In another aspect, a three dimensional structural frame is disclosed, where the transverse stiffener is welded to the first flange, the web, and the second flange of the three dimensional structure.","In another aspect, a three dimensional structural frame is disclosed.","The three dimensional structural frame includes two three dimensional structural frames connected at their first ends.","In another aspect, a three dimensional structural frame is disclosed, further including a connector for a fall protection harness between the firsts ends of the two three dimensional structural frame members.","In another aspect, a three dimensional structural frame is disclosed.","The three dimensional structural frame includes a frame member that includes an elongated three dimensional structure having a first side, a second side, and a center support portion, where the first side has a variable cross section from a first end to the center support portion, and where the second side has a variable cross section from a second end to the center support portion, the frame member further includes mounting flanges at the first end and the second end that at least partially enclose the first end and the second end, where the mounting flanges include through holes for mounting the frame member; a center support mounted at the center support portion; and transverse stiffeners positioned within the three dimensional structure on the first side and the second side that includes a rigid support structure rigidly fixed to a first flange, a web, and a second flange of the three dimensional structure.","In another aspect, a three dimensional structural frame is disclosed, where the frame member is a single piece of sheet metal.","In another aspect, a three dimensional structural frame is disclosed, where the center support includes a connector for a fall protection harness.","In another aspect, a three dimensional structural frame is disclosed, where the transverse stiffeners are welded to the first flange, the web, and the second flange of the three dimensional structure.","In another aspect, an enclosure is disclosed.","The enclosure includes a plurality of three dimensional structural frames; and opposing wall portions interconnected by the plurality of three dimensional structural frames, where the wall portions include a plurality of uniform wall sections, where the wall sections include a wall panel portion, a top wall portion, and sidewall portions, where the sidewall portions of the plurality of wall sections are joined to form the wall portions, where the plurality of three dimensional structural frames are attached to the top wall portions of the wall sections.","In another aspect, an enclosure is disclosed, where the ends of the three dimensional structural frames overlap and are simultaneously attached to two wall sections.","In another aspect, an enclosure is disclosed, where the wall sections include a single piece of formed sheet metal.","In another aspect, an enclosure is disclosed, further including a plurality of support members, where the support members extend between the opposing wall portions.","In another aspect, an enclosure is disclosed, where the wall sections include a bottom wall portion.","In another aspect, an enclosure is disclosed, where the sidewalls of the plurality of wall sections are connected by a plurality of rivets.","In another aspect, an enclosure is disclosed, further including a gasket between the sidewall portions.","In another aspect, an enclosure is disclosed, where the gasket includes a silicone bead, polyurethane, or structural adhesive.","In another aspect, an enclosure is disclosed, further including a roof that includes a plate secured to the three dimensional structural frames.","In another aspect, an enclosure is disclosed, where the plate includes sheet metal.","In another aspect, an enclosure is disclosed, where the plate includes perforated sheet metal.","In another aspect, an enclosure is disclosed, where the roof further includes a weatherproof membrane overlaying the plate and attached to the wall panel portions of the wall sections.","In another aspect, an enclosure is disclosed, further including a first support member connected to a first group of wall sections, and a second support member connected to a second group of wall sections.","In another aspect, an enclosure disclosed, further including a strengthening member connected to the plurality of three dimensional structural frames.","In another aspect, a lift plate for engaging the ends of a plurality of three dimensional structural frames is disclosed.","The lift plate includes a planar portion that includes a series of a pattern of mounting holes for receiving hardware for securing the plate to the ends of the plurality of frames; and a connecting portion for engaging a harness that provides upward force to lift the plate and the frames.","In another aspect, a lift plate is disclosed, where the connecting portion includes a reinforcement plate.","In another aspect, a lift plate is disclosed, where the connecting portion includes two reinforcement plates.","In another aspect, a liftable enclosure is disclosed.","The liftable enclosure includes a plurality of the three dimensional structural frames; and at least two lift plates that include a planar portion that includes a series of a pattern of mounting holes for receiving hardware for securing the plate to the ends of the plurality of frames and a connecting portion for engaging a harness that provides an upward force to lift the plate and the frames.","In another aspect, a liftable enclosure is disclosed, further including opposing walls interconnected by the plurality of three dimensional structural frames, where the walls include a plurality of uniform wall sections, where the wall sections include a wall panel portion, a top wall portion, and sidewall portions, where the sidewall portions of the plurality of wall sections are connected to form at least a portion of a wall of the enclosure, where the plurality of three dimensional structural frames are attached to the top wall portions of the wall sections.","In another aspect, a liftable enclosure is disclosed, where the lift plates are further connected to the wall panel portions of the wall sections.","In another aspect, a method for building a structure is disclosed.","The method includes fabricating opposing walls of the structure by attaching sidewall portions of a plurality of wall sections comprising a wall panel portion, a top wall portion, and sidewall portions, where the sidewall portions of the plurality of wall sections; and attaching a plurality of three dimensional structural frames to the top walls portions of the wall sections of the opposing walls.","In another aspect, a method is disclosed, where the opposing walls are fabricated while the sidewall portions are substantially horizontal.","In another aspect, a method is disclosed, where the opposing walls are uprighted by attaching a lift plate to a top end of a plurality of wall sections and lifting the top end.","In another aspect, a method for lifting an enclosure is disclosed.","The method includes attaching a plurality of lift plates to the a plurality of the ends of the three dimensional structural frames and the wall panel sections of the opposing walls; attaching a harness to the plurality of lift plates; and lifting the structure with an upward force to the harness, where the lift plates include a planar portion that includes a series of a pattern of mounting holes for receiving hardware for securing the plate to the ends of the plurality of frames and the wall panel sections, and a connecting portion for attaching the harness.","BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings, which are included to provide a further understanding of the disclosure, are incorporated in and constitute a part of this specification, illustrate embodiments of the disclosure, and together with the detailed description serve to explain the principles of the invention.","No attempt is made to show structural details of the invention in more detail than may be necessary for a fundamental understanding of the invention and various ways in which it may be practiced.","FIG.","1 shows a three dimensional structural frame member, according to an example embodiment.","FIG.","1-1 shows aspects of the three dimensional structural frame member depicted in FIG.","1, according to an example embodiment.","FIG.","2 shows aspects of a three dimensional structural frame member, according to an example embodiment.","FIG.","3a shows a three dimensional structural frame, according to an example embodiment.","FIG.","3a-1 shows aspects of the three dimensional structural frame depicted in FIG.","3a, according to an example embodiment.","FIG.","3b shows a back view of the three dimensional structural frame depicted in FIG.","3a, according to an example embodiment.","FIG.","3c shows a top view of the three dimensional structural frame depicted in FIG.","3a, according to an example embodiment.","FIG.","3d shows a front view of the three dimensional structural frame depicted in FIG.","3a, according to an example embodiment.","FIG.","4 shows a three dimensional structural frame, according to an example embodiment.","FIG.","4-1 shows aspects of the three dimensional structural frame depicted in FIG.","4, according to an example embodiment.","FIG.","5 shows a three dimensional structural frame, according to an example embodiment.","FIG.","6 shows a three dimensional structural frame, according to an example embodiment.","FIG.","7 shows a three dimensional structural frame, according to an example embodiment.","FIG.","8 shows an enclosure, according to an example embodiment.","FIG.","9 shows a wall section, according to an example embodiment.","FIG.","9-1 shows aspects of the wall section depicted in FIG.","9, according to an example embodiment.","FIG.","10a shows three dimensional structural frames connected to wall sections, according to an example embodiment.","FIG.","10b shows wall sections connected to a support member, according to an example embodiment.","FIG.","10c shows a side view of the plurality of wall sections connected to the support member depicted in FIG.","10b, according to an example embodiment.","FIG.","10c-1 shows aspects of the sections connected to the support member depicted in FIG.","10c, according to an example embodiment.","FIG.","11a shows aspects of a roof of an enclosure, according to an example embodiment.","FIG.","11b shows three dimensional structural frames connected to a strengthening member, according to an example embodiment.","FIG.","11b-1 shows aspects of the three dimensional structural frames connected to a strengthening member depicted in FIG.","11b, according to an example embodiment.","FIG.","12a shows an enclosure, according to an example embodiment.","FIG.","12b shows a mounting surface, according to an example embodiment.","FIG.","13 shows a lift plate, according to an example embodiment.","FIG.","14a shows a lift plate, according to an example embodiment.","FIG.","14b shows a perspective view of the lift plate shown in FIG.","14a, according to an example embodiment.","FIG.","14c shows a side view of the lift plate shown in FIG.","14a, according to an example embodiment.","FIG.","15a shows a liftable enclosure, according to an example embodiment.","FIG.","15a-1 shows aspects of the liftable enclosure shown in FIG.","15a, according to an example embodiment.","FIG.","16 shows a method for building a structure, according to an example embodiment.","FIG.","17 shows a method for lifting an enclosure, according to an example embodiment.","DESCRIPTION I.","Introduction It may be desirable to lift enclosures in a variety of situations.","As one example, when an enclosure surrounds equipment (e.g., a generator, related electrical, electronic, and mechanical components, and a fuel tank) it may be desirable to lift the enclosure to access the equipment for repair or replacement.","As another example, it may be desirable to lift an enclosure during installation or fabrication of the enclosure.","In its various aspects, the disclosure is directed to three dimensional structural frames and enclosures and related methods.","In an example embodiment, an enclosure may include three dimensional structural frames and opposing walls interconnected by the three dimensional structural frames, and lift plates may be connected to the three dimensional structural frames.","The lift plates may be used to lift the enclosure upward.","With this arrangement, the enclosure may be lifted without partially disassembling the enclosure.","Beneficially, embodiments described herein may reduce labor, equipment, and/or time needed to lift enclosures.","In addition, embodiments described herein may reduce damage to the enclosure after or while the enclosure is lifted, such as excessive deformation of portions of the enclosure, plastic deformation of portions of the enclosure, and/or buckling of portions of the enclosure.","Accordingly, embodiments described herein may help to reduce costs of lifting enclosures.","II.","Example Apparatus A.","Three Dimensional Structural Frame Members FIG.","1 shows a three dimensional structural frame member 100, according to an example embodiment.","The three dimensional structural frame member 100 includes a frame member 110, a mounting flange 120, and a transverse stiffener 130.Moreover, the frame member 110 includes a variable cross section three dimensional structure 112 that includes a first end 114, a second end 116, a first (bottom) flange 140 that may define a first interior wall, a web 142 that may define a second interior wall, and a second (top) flange 144 that may define a third interior wall.","The first end 114 is wider than the second end 116.With this arrangement, the variable cross section three dimensional structure 112 may comprise an open three dimensional structure comprising the first flange 140, the web 142, and the second flange 144.The frame member 110 may comprise a variety of materials.","For instance, in some embodiments, the frame member 110 may comprise steel.","And in some such embodiments, the frame member 110 may comprise sheet metal of variable thickness and post processing treatments.","Moreover, in some embodiments, the variable cross section three dimensional structure 112 may comprise a single piece of sheet metal.","Further, in some embodiments, the variable cross section three dimensional structure 112 and mounting flange 120 may comprise a single piece of sheet metal.","The variable cross section three dimensional structure 112 and mounting flange 120 may comprise the same or similar material as the frame member 110.As shown in FIG.","1, the mounting flange 120 may be located at the second end 116 of the variable cross section three dimensional structure 120 and at least partially enclose the second end 116.The mounting flange 120 may include through holes 122 for mounting the frame member 110.In the illustrated example, the mounting flange 120 may further include second through holes 124, and the first end 114 may further include third through holes 118.Further, as shown in FIG.","1, the transverse stiffener 130 may be positioned within the variable cross section three dimensional structure 112 and comprises a rigid support structure rigidly fixed to the first flange 140, the web 142, and the second flange 144 of the variable cross section three dimensional structure 112.In some embodiments, the transverse stiffener 130 may be welded to the first flange 140, the web 142, and the second flange 144 of the variable cross section three dimensional structure 112 as shown in FIG.","1-1.And in some such embodiments, the transverse stiffener 130 may be fillet welded to each of the first flange 140, the web 142, and the second flange 144.The first flange 140, the web 142, and the second flange 144 may take various different forms in various different embodiments.","For instance, in some embodiments, the first flange 140, the web 142, and the second flange 144 may have the same thickness.","However, in other embodiments, at least two of the first flange 140, the web 142, and the second flange 144 may have different thicknesses.","Moreover, in some embodiments, each of the first flange 140, the web 142, and the second flange 144 may have different thicknesses.","The first flange 140, the web 142, and the second flange 144 may have other parameters that are the same or different as well.","For instance, any XYZ dimension of the first flange 140 may be the same as or different than the corresponding XYZ dimension of the web 142 and/or the second flange 144, such as width, depth, and height.","Further, the moment of inertia of the first flange 140 may be the same as or different than the moment of inertia of the web 142 and/or the second flange 144.Moreover, in some embodiments, the first flange 140, the web 142, and/or the second flange 144 may have varying thicknesses, varying XYZ dimensions, and/or varying moments of inertia.","The transverse stiffener 130 may comprise a variety of materials in variable thicknesses.","For instance, in some embodiments, the transverse stiffener 130 may comprise the same or similar material as the frame member 110.However, in other embodiments, the transverse stiffener 130 may comprise a different material than the frame member 110.Further still, as shown in FIG.","1, the three dimensional structural frame member 100 may further include a second transverse stiffener 132 positioned within the variable cross section three dimensional structure 112 and comprise a rigid support structure rigidly fixed to the first flange 140, the web 142, and the second flange 144 of the variable cross section three dimensional structure 112.The second transverse stiffener 132 may comprise any of the materials that the transverse stiffener 130 comprises.","In some embodiments, the second transverse stiffener 132 may comprise the same or similar material as the first transverse stiffener 130 and/or the frame member 110.However, in other embodiments, the second transverse stiffener 132 may comprise a different material than the transverse stiffener 130 and/or the frame member 110.The second transverse stiffener 132 may be welded to the first flange 140, the web 142, and the second flange 144 in the same or similar way as the transverse stiffener 130 is welded to the first flange 140, the web 142, and the second flange 144.The transverse stiffener 130 and/or the second transverse stiffener 132 may strengthen the three dimensional structural frame member 100, for example, by improving resistance of the three dimensional structural frame member 100 to deformation, bending, rupturing, breaking, and other modes of failure.","The location of the transverse stiffener 130 in the variable cross section three dimensional structure 112 with respect to the first end 114 and the second end 116 may be selected based on predetermined loading of the three dimensional structural frame member 100 (e.g., bending moments and/or torsional loading).","Similarly, the location of the second transverse stiffener 132 in the variable cross section three dimensional structure 112 with respect to the first end 114 and second end 116 and/or the transverse stiffener 130 may be selected based on predetermined loading of the three dimensional structural frame member 100.Other parameters of the three dimensional structural frame member 100 may be selected based on predetermined loading of the three dimensional structural frame member 100 as well, such as the material or thickness of the frame member 110, width of the first end 116, and width of the second end 118.FIG.","2 shows aspects of a three dimensional structural frame member 200, according to an example embodiment.","The three dimensional structural frame member 200 is similar to three dimensional structural frame member 100, except that the three dimensional structural frame member 200 includes a three dimensional structure 212 that does not have a variable cross section.","Instead, the three dimensional structure 212 includes two ends that have substantially equal widths.","For instance, a first end (not shown in FIG.","2) has a first width, a second end 216 has a second width, and the first width and the second width are substantially equal.","With this arrangement, the three dimensional structure 212 may have a constant cross section.","The term “substantially equal,” as used in this disclosure, means exactly equal or one or more deviations from exactly equal that do not significantly impact lifting enclosures as described herein.","As shown in FIG.","2, the three dimensional structural frame member 200 includes a frame member 210 that has the second end 216, a mounting flange 220 at the second end 216 that at least partially encloses the second end 216, and a transverse stiffener 230 positioned within the three dimensional structure 212 comprising a rigid support structure rigidly fixed to a first (bottom) flange 240 that may define a first interior wall, a web 242 that may define a second interior wall, and a second (top) flange 244 that may define a third interior wall of the three dimensional structure 212.In addition, as shown in FIG.","2, the three dimensional structural frame member 200 may further include a second transverse stiffener 232 positioned within the three dimensional structure 212 comprising a rigid support structure rigidly fixed to the first flange 240, the web 242, and the second flange 244.The three dimensional structural frame member 200 may also include through holes, second through holes, and third through holes similar to through holes 122, second through holes 124, and third through holes 118 in the three dimensional structural frame member 100.Components of the three dimensional structural frame member 200 of FIG.","2 may have the same or similar arrangement and function in a similar manner as similarly numbered components of the three dimensional structural frame member 100 of FIG.","1 unless otherwise noted.","For instance, in some embodiments, the three dimensional structure 212 may comprise a single piece of sheet metal.","Moreover, in some embodiments, the three dimensional structure 212 and mounting flange 220 may comprise a single piece of sheet metal.","Further, in some embodiments, the three dimensional structure 212 may comprise an open three dimensional structure comprising the first flange 240, the web 242, and the second flange 244.Further still, in some embodiments, the transverse stiffener 230 may be welded to the first flange 240, the web 242, and the second flange 244 of the three dimensional structure 212.The transverse stiffener 230 may be welded to the first flange 240, the web 242, and the second flange 244 of the three dimensional structure 212 in the same or similar way as the transverse stiffener 130 is welded to the first flange 140, the web 142, and the second flange 144 of the three dimensional structure 112.In addition, the second transverse stiffener 232 may be welded to the first flange 240, the web 242, and the second flange 244 of the three dimensional structure 212 in the same or similar way as the transverse stiffener 230 is welded to the first flange 240, the web 242, and the second flange 244 of the three dimensional structure 212.B.","Three Dimensional Structural Frames FIG.","3a shows a three dimensional structural frame 300, according to an example embodiment.","Three dimensional structural frame 300 includes a first three dimensional structural frame member 300A and a second three dimensional structural frame member 300B joined together at their first ends 314A, 314B by a plurality of fasteners 350 as shown in FIG.","3a-1.In some embodiments, the plurality of fasteners 350 may comprise three fasteners.","And in some such embodiments, the fasteners of the plurality of fasteners 350 may comprise screws.","Moreover, in some embodiments, the plurality of fasteners 350 may be installed in through holes in first ends 314A, 314B similar to through holes 118 in three dimensional structural frame member 100.In the illustrated example, the first three dimensional structural frame member 300A and second three dimensional structural frame member 300B may take the form of or be similar in form to the three dimensional structural frame member 100.Accordingly, components of the first three dimensional structural frame member 300A of FIG.","3a may have the same arrangement and function in a similar way as similarly numbered components of the three dimensional structural frame member 100 of FIG.","1, and components of the second three dimensional structural frame member 300B of FIG.","3a may have the same arrangement and function in a similar way as the similarly numbered components of the three dimensional structural frame member 100 of FIG.","1.FIG.","3b shows a back view of the three dimensional structural frame 300.Further, FIG.","3c shows a top view of the three dimensional structural frame 300, and FIG.","3d shows a front view of the three dimensional structural frame 300.As shown in FIGS.","3b and 3c, the three dimensional structural frame 300 may further include a support beam 360 connected to the three dimensional structure 312A of the first three dimensional structural frame member 300A and the three dimensional structure 312B of the second three dimensional structural frame member 300B.","The support beam 360 may comprise the same or similar material as the frame member 110.In some embodiments, a three dimensional structural frame may include a connector for a fall protection harness (which may be referred to as a fall prevention cleat).","FIG.","4 shows a three dimensional structural frame 400 that includes a connector 470 for a fall protection harness, according to an example embodiment.","The three dimensional structural frame 400 includes a first three dimensional structural frame member 400A and a second three dimensional structural frame member 400B joined together at their first ends 414A and 414B by a plurality of fasteners 450 as shown in FIG.","4-1.As shown in FIGS.","4 and 4-1, the connector 470 is between the first end 414A of the first three dimensional structural frame member 400A and the first end 414B of the second three dimensional structural frame member 400B.","With this arrangement, the plurality of fasteners 450 may join the connector 470 to the first three dimensional structural frame member 400A and the second three dimensional structural frame member 400B.","Moreover, in some embodiments, the connector 470 may be welded to the three dimensional structure 412A of the first three dimensional structural frame member 400A and/or the three dimensional structure 412B of the second three dimensional structural frame member 400B.","In some examples, the connector 470 may be fillet welded to the three dimensional structure 412A and/or the three dimensional structure 412B.","The connector 470 may comprise a variety of materials.","For instance, in some embodiments, the connector 470 may comprise steel.","And in some such embodiments, the connector 470 may comprise ½ inch hot rolled steel (HRS).","Further, in some embodiments, the connector 470 may strengthen the three dimensional structural frame 400 in the same or similar way as the transverse stiffener 130 and/or the second transverse stiffener 132 strengthen the three dimensional structural frame member 100.In the illustrated example, the first three dimensional structural frame member 400A may take the form of or be similar in form to the first three dimensional structural frame member 300A, and second three dimensional structural frame member 400B may take the form of or be similar in form to the second three dimensional structural frame member 300B.","Accordingly, the first three dimensional structural frame member 400A may have the same arrangement and function in a similar way as the first three dimensional structural frame member 300A, and the second three dimensional structural frame member 400B may have the same arrangement and function in a similar way as the second three dimensional structural frame member 300B.","Moreover, in some embodiments, three dimensional structural frames may have more than one connector for a fall protection harness.","FIG.","5 shows a three dimensional structural frame 500 that includes a connector 570 for a fall protection harness, a second connector 572 for the fall protection harness, and a third connector 574 for the fall protection harness.","The three dimensional structural frame 500 includes a first three dimensional structural frame member 500A and a second three dimensional structural frame member 500B joined together at their first ends 514A and 514B by a plurality of fasteners 550.The connector 570 may be between the first end 514A of the first three dimensional structural frame member 500A and the first end 515B of the second three dimensional structural frame member 500B.","In addition, the connector 570 may be joined in the three dimensional structural frame 500 in the same or similar way as the connector 470 may be joined in the three dimensional structural frame 400.In addition, the second connector 572 may be located between the first end 514A and the second end 516A of the first three dimensional structural frame member 500A.","In some embodiments, the second connector 572 may be welded to the three dimensional structure 512A of the first three dimensional structural frame member 500A in the same or similar way as the connector 470 is welded to the three dimensional structure 412A and/or the three dimensional structure 412B.","Moreover, the third connector 574 may be located between the first end 514B and the second end 516B of the second three dimensional structural frame member 500B.","In some embodiments, the third connector 574 may be welded to the three dimensional structure 512B of the second three dimensional structural frame member 500B in the same or similar way as the connector 470 is welded to the three dimensional structure 412A and/or the three dimensional structure 412B.","Further, in some embodiments, the connector 570, the second connector 572, and the third connector 574 may strengthen the three dimensional structural frame 500 in the same or similar way as the transverse stiffener 130 and/or the second transverse stiffener 132 strengthen the three dimensional structural frame member 100.In the illustrated example, the first three dimensional structural frame member 500A may take the form of or be similar in form to the first three dimensional structural frame member 300A, and second three dimensional structural frame member 500B may take the form of or be similar in form to the second three dimensional structural frame member 300B.","Accordingly, the first three dimensional structural frame member 500A may have the same arrangement and function in a similar way as the first three dimensional structural frame member 300A, and the second three dimensional structural frame member 500B may have the same arrangement and function in a similar way as the second three dimensional structural frame member 300B.","In some embodiments, a three dimensional structural frame may be comprised of a single member.","FIG.","6 shows a three dimensional structural frame 600, according to an example embodiment.","The three dimensional structural frame includes a frame member 610, mounting flanges 620 and 630, a center support 640, and transverse stiffeners 650 and 652.The frame member 610 includes an elongated three dimensional structure 612 that has a first side 614, a first end 615, a second side 616, a second end 617, and a center support portion 618.The first side 614 has a variable cross section from the first end 615 to the center support portion 618, and the second side 616 has a variable cross section from the second end 617 to the center support portion 618.The elongated three dimensional structure 612 further includes a first (bottom) flange 660 that may define a first interior wall, a web 662 that may define a second interior wall, and second (top) flange 664 that may define a third interior wall.","With this arrangement, the elongated three dimensional structure 612 may comprise an open three dimensional structure with the first flange 660, the web 662, and the second flange 664 and may have a varying cross section.","The frame member 610 may comprise the same or similar material as the frame member 110.As shown in FIG.","6, the mounting flange 620 may be located at the first end 615 and at least partially enclose the first end 615, and the mounting flange 630 may be located at the second end 616 and at least partially enclose the second end 616.The mounting flange 620 may include through holes 622 for mounting the frame member 610.In the illustrated example, the mounting flange 620 may further include second through holes 624.The mounting flange 630 in turn may include through holes 632 for mounting the frame member 610.In the illustrated example, the mounting flange 630 may further include second through holes 634.The frame member 610 may comprise the same or similar material as the frame member 110.Moreover, in some embodiments, the elongated three dimensional structure 612 may comprise a single piece of sheet metal.","Further, in some embodiments, the elongated three dimensional structure 612 and mounting flanges 620, 630 may comprise a single piece of sheet metal.","The elongated three dimensional structure 612 and mounting flanges 620 and 630 may comprise the same or similar material as the frame member 610.Further, as shown in FIG.","6, the center support 640 is mounted at the center support portion 618.The center support 640 may comprise the same or similar material as the frame member 610.Further still, as shown in FIG.","6, the transverse stiffener 650 is positioned within the elongated three dimensional structure 612 on the first side 614 of the elongated three dimensional structure 612 and comprises a rigid support structure rigidly fixed to the first flange 660, the web 662, and the second flange 664, and the transverse stiffener 652 is positioned within the elongated three dimensional structure 612 on the second side 616 of the elongated three dimensional structure 612 and comprises a rigid support structure rigidly fixed to the first flange 660, the web 662, and the second flange 664.In some embodiments, the transverse stiffeners 650, 652 may be welded to the first flange 660, the web 662, and the second flange 664 in the same or similar way as the transverse stiffener 130 is welded to the first flange 340, the web 342, and the second flange 344.The transverse stiffeners 650, 652 may comprise a variety of materials in variable thicknesses.","For instance, in some embodiments, the transverse stiffeners 650, 652 may comprise the same or similar material as the frame member 610.However, in other embodiments, the transverse stiffeners 650, 652 may comprise a different material than the elongated three dimensional structure 612.Further still, as shown in FIG.","6, the three dimensional structural frame 600 may further include a second transverse stiffener 654 within the elongated three dimensional structure 612 on the first side 614 of the elongated three dimensional structure 612 and comprises a rigid support structure rigidly fixed to the first flange 660, the web 662, and the second flange 664, and a second transverse stiffener 656 within the elongated three dimensional structure 612 on the second side 616 of the elongated three dimensional structure 612 and comprises a rigid support structure rigidly fixed to the first flange 660, the web 662, and the second flange 664.The second transverse stiffeners 654, 656 may comprise any of the materials that the transverse stiffeners 650, 652 comprise.","In some embodiments, the second transverse stiffeners 654, 656 may comprise the same or similar material as the transverse stiffeners 650, 652 and/or the frame member 610.However, in other embodiments, the second transverse stiffeners 654, 656 may comprise a different material than the transverse stiffeners 650, 652 and/or the frame member 610.The second transverse stiffeners 650, 652 may be welded to the first flange 660, the web 662, and the second flange 664 in the same or similar way as the transverse stiffeners 650, 652 are welded to the first flange 660, the web 662, and the second flange 664.The transverse stiffeners 650, 652 and/or the second transverse stiffener 654, 656 may strengthen the three dimensional structural frame 600, for example, by improving resistance of the three dimensional structural frame 600 to deformation, bending, rupturing, breaking and other modes of failure.","Similarly, the center support 640 may strengthen the three dimensional structural frame 600, for example, by improving resistance of the three dimensional structural frame 600 to deformation, bending, rupturing, breaking and other modes of failure.","The location of the transverse stiffeners 650, 652 in the elongated three dimensional structure 612 with respect to the first end 615 and the second end 617 may be selected based on predetermined loading of the three dimensional structural frame 600.Similarly, the location of the second transverse stiffeners 654, 656 in the elongated three dimensional structure 612 with respect to the first end 615 and second end 617 and/or the transverse stiffeners 650, 652 may be selected based on predetermined loading of the structural frame 600.Other parameters of the three dimensional structural frame member 600 may be selected on predetermined loading of the three dimensional structural frame member 600 as well, such as the material or thickness of the frame member 610, width of the first end 615, and width of the second end 617.In some embodiments, a three dimensional structural frame that includes a single three dimensional structure may include a connector for a fall protection harness.","FIG.","7 shows a three dimensional structural frame 700 that includes a connector 770 for a fall protection harness, according to an example embodiment.","The three dimensional structural frame 700 includes a frame member 710, mounting flanges 720 and 730, a center support 740, transverse stiffeners 750 and 752, and second transverse stiffeners 754 and 756.Components in the three dimensional structural frame 700 of FIG.","7 may have the same or similar arrangement and function in a similar manner as similarly numbered components of the three dimensional structural frame 600 of FIG.","6 unless otherwise noted.","As shown in FIG.","7, the center support includes the connector 770.The connector 770 may take the form of or be similar in form to the connector 470.In some embodiments, the connector 770 may strengthen the three dimensional structural frame 700 in the same or similar way that the transverse stiffeners 650, 652 and/or the second transverse stiffeners 654, 656 strengthen the three dimensional structural frame 600.In some embodiments, a three dimensional structural frame that includes a single three dimensional structure may have two or more connectors for a fall protection harness.","For instance, in some embodiments, a three dimensional structural frame that includes a single three dimensional structure may have three connectors arranged in the same or similar was as connectors 570, 572, and 574 are arranged in the three dimensional structural frame 500.In addition, in some embodiments, three dimensional structural frames may include a three dimensional structure that has a constant cross section similar to the three dimensional structure 212.For instance, in some embodiments, a structural frame may comprise two three dimensional structural frame members that are joined at their first ends, where each three dimensional structural frame member takes the form of or is similar in form to the three dimensional structural frame member 200.And in some such embodiments, the three dimensional structural frame may include one or more connectors similar to connector 470.Moreover, in some embodiments, a three dimensional structural frame may comprise a single three dimensional structure with a constant cross section similar to the cross section of three dimensional structure 212.And in some such embodiments, the three dimensional structural frame may include one or more connectors similar to connector 470.Further, in some embodiments, a three dimensional structural frame may comprise a first three dimensional structural frame member that takes the form of or is similar in form to the three dimensional structural frame member 100 and a second three dimensional structural frame member that takes the form of or is similar in form to the three dimensional structural frame member 200, where the first and second three dimensional structural frame members are joined at their first ends.","And in some such embodiments, the three dimensional structural frame may include one or more connectors similar to connector 470.C.","Enclosures FIG.","8 shows an enclosure 800, according to an example embodiment.","The enclosure includes a plurality of three dimensional structural frames 810, opposing wall portions 820 interconnected by the plurality of three dimensional structural frames 810, and a roof 840 secured to the plurality of the three dimensional structural frames 810.In some embodiments, the enclosure 800 may have length of forty five feet.","The plurality of three dimensional structural frames 810 may take various different forms in various different embodiments.","For purposes of illustration, the plurality of three dimensional structural frames 810 includes four three dimensional structural frames 812, 814, 816, 818.However, in other examples, the plurality of three dimensional structural frames 810 may include more or less than four three dimensional structural frames.","The number of three dimensional structural frames in the plurality of three dimensional structural frames 810 may be selected based in part on a predetermined length and/or loading of the enclosure 800.The three dimensional structural frames 812, 814, 816, and 818 may comprise any of the three dimensional structural frames described herein, including the three dimensional structural frames 300, 400, 500, 600, and 700 and example three dimensional structural frames that include a three dimensional structure that has a constant cross section.","In some embodiments, the three dimensional structural frames 812, 814, 816, and 818 may be the same as each other.","However, in other embodiments, two or more of the three dimensional structural frames 812, 814, 816, and 818 may be different.","With this arrangement, the plurality of three dimensional structural frames 810 may comprise a combination of any of the three dimensional structural frames described herein.","The opposing wall portions 820 include a plurality of uniform wall sections 830.For purposes of illustration, the plurality of wall sections 830 includes four wall sections 832, 834, 836, and 838.However, in other examples, plurality of wall sections 830 may include more or less than four wall sections.","FIG.","9 shows aspects of a wall section 900, according to an example embodiment.","The wall sections 832, 834, 836, and 838 may take the form of or be similar in form to the wall section 900.The wall section 900 includes a wall panel portion 910, a top wall portion 920, sidewall portions 930A, 930B, and a bottom wall portion 940.In some embodiments, the wall section 900 may comprise a single piece of formed sheet metal.","Moreover, in some embodiments, the wall section 900 may comprise steel.","Further, in some embodiments, the wall section 900 may be the same or similar material as the frame member 110.The sidewall portions 930A, 930B may be joined to sidewall portions of other wall sections to form opposing wall portions, such as the opposing wall portions 820.The bottom wall portion 940 is further shown in FIG.","9-1.For instance, the bottom wall portion 940 may include a support flange 942 that wraps around the bottom wall portion 940.With this arrangement, the support flange 942 may strengthen the bottom wall portion 940, for example, by improving resistance of the bottom wall portion 940 to deformation, bending, rupturing, breaking, and other modes of failure.","The support flange 942 includes a through hole 944.Further, as shown in FIG.","9-1, the bottom wall portion 940 includes a through hole 946.When wall section 900 is part of opposing walls of an enclosure, such as opposing walls 820 of enclosure 800, a fastener may be installed in through hole 946 to secure wall section 900 to ground or a mounting surface that the enclosure is located over, such as a skid or frame on which equipment is disposed.","FIG.","10a shows three dimensional structural frames 1010 attached to walls sections 1030, according to an example embodiment.","In particular, FIG.","10a shows five three dimensional structural frames 1010A-E connected to four wall sections 1030A-D.","The three dimensional structural frames 1010A-E have through holes 1012A-E, respectively and the wall sections 1030A-D have through holes 1032A-D, respectively.","The three dimensional structural frames 1010A-E may take the form of any of or be similar in form to any of the three dimensional structural frames described herein, and the wall sections 1030A-D may take the form of or be similar in form to the wall section 900.As shown in FIG.","10a, a three dimensional structural frame is attached to a top wall portion, such as top wall portion 940, of a wall section.","Moreover, as shown in FIG.","10a, in some embodiments, the ends of certain three dimensional structural frames overlap and are simultaneously attached to two wall sections.","For instance, the end of three dimensional structural frame 1010B overlaps and is simultaneously attached to wall section 1030A and wall section 1030B, the end of three dimensional structural frame 1010C overlaps and is simultaneously attached to wall section 1030B and 1030C, and the end of three dimensional structural frame 1010D overlaps and is simultaneously attached to wall section 1030C and wall section 1030D.","Three dimensional structural frames 1010 may be attached to wall sections by hardware (e.g., fasteners) installed in through holes, such as through holes 122, 322A and 322B, and 622 and 632.Moreover, wall sections 1010 may be connected by sidewall portions, such as sidewall portions 930A and 930B.","In some embodiments, sidewall portions may be connected by a plurality of rivets (not shown).","And in some such embodiments, the plurality of rivets may comprise one rivet per six inch length of the sidewall portion.","Further, in some embodiments, a gasket may be located between wall sections, such as a gasket 1040 is located between wall section 1030A and wall section 1030B.","As shown in FIG.","10a, the gasket 1040 may be located between the sidewall portion of wall section 1030A and the sidewall portion of wall section 1030B.","In some embodiments, gasket 1040 may comprise a silicone bead, polyurethane, or structural adhesive (e.g., weatherproof adhesive).","In addition, in some embodiments, gasket 1040 may weatherproof the plurality of rivets used to join the wall sections.","Further still, in some embodiments, the enclosure may further include a plurality of support members that extend between the opposing wall portions (not shown in FIG.","8).","In some embodiments, the plurality of support members may have the same or similar material as the frame member 110.The plurality of support members may strengthen the enclosure, for example, by improving resistance of the enclosure 800 to plastic deformation and/or buckling.","Moreover, in some embodiments, a roof of an enclosure, such as the roof 840, may include a plate (or a plurality of plates) secured to the three dimensional structural frames.","And in some such embodiments, the plate may comprise sheet metal and/or perforated sheet metal.","Further, in some embodiments, the roof can further include a weatherproof membrane (or a plurality of membranes) overlaying the plate and attached to wall panel portions of wall sections.","FIG.","10b shows wall sections 1080 connected to a support member 1090, according to an example embodiment.","The enclosure 800 may further include one or more support members that may take the form of or be similar in form to the support member 1090.The support member 1090 may tie each of the wall sections 1080 together.","In addition, the support member 1080 may act as a lateral brace, improve rigidity of the wall sections 1080, and/or improve resistance of the wall sections 1080 to shear loading, torsional loading, and axial loading.","As shown in FIG.","10b, the wall sections 1080 include twelve wall sections 1080A-L.","However, in other examples, the wall sections 1080 may include more or less than twelve wall sections.","The number of wall sections in the wall sections 1080 may be selected based in part on a predetermined length and/or loading of an enclosure.","In the illustrated example, certain wall sections of the wall sections 1080 may have different lengths (e.g., wall sections 1080A and 1080D) and/or different widths (e.g., wall sections 1080A, 1080D, and 1080H).","The support member 1090 may take various different forms in various different embodiments.","In some embodiments, the support member 1090 may comprise steel.","Moreover, in some embodiments, the support member 1090 may be connected to an end of each wall section of the wall sections 1080, such as a top end of the wall section when the wall section is oriented substantially perpendicular to ground.","The term “substantially perpendicular,” as used in this disclosure, refers to exactly perpendicular or one or more deviations from exactly perpendicular that do not significantly impact lifting an enclosure as described herein.","FIG.","10c shows a side view of the wall sections 1080 connected to the support member 1090, and FIG.","10c-1 shows aspects of the wall sections 1080 connected to the support member 1090.As shown in FIG.","10c-1, in some embodiments, the support member 1090 may have a C-shaped cross section.","And in some such embodiments, the support member 1090 may be oriented, such that an open portion 1092 of its cross section may face away from the wall sections 1080.Other cross sectional shapes of the support member 1090 are possible as well, including rectangular or triangular.","The length of the support member 1090 may be selected based at least in part on the number of wall sections in the wall sections 1080.In addition, the thickness of the support member 1090 may be selected based at least in part on a predetermined loading of the wall sections 1080 and/or an enclosure (e.g., the thickness of the support member 1090 may increase as the predetermined loading increases).","In addition, the support member 1090 may define a wire way for electrical cabling associated with an enclosure.","In some embodiments, the wire way may be partitioned to separate electrical cabling for AC circuits associated with the enclosure and electrical cabling for DC circuits associated with the enclosure.","Moreover, in some embodiments, after electrical cabling is installed in the support member 1090, a closing plate (not shown) may be connected over the open portion 1092 of the support member 1090.With this arrangement, the closing plate may help to seal and protect the electrical cabling.","An enclosure may include at least two support members that take the form of the support member 1090.A first support member may be connected to a first group of wall sections and a second support member may be connected to a second group of wall sections.","The first group of wall sections may be substantially parallel to the second group of wall sections.","With this arrangement, the first support member may be substantially parallel to the second support member.","FIG.","11a shows aspects of a roof 1100 of an enclosure, according to an example embodiment.","The roof 840 may take the form of or be similar in form to the roof 1100.As shown in FIG.","11a, the roof 1100 includes plates attached to three dimensional structural frames.","In particular, plate 1110A and plate 1110B are secured to three dimensional structural frames 1120 and 1122.Plates 1110A and plates 1110B may be secured to three dimensional structural frames 1120 and 1122 by hardware.","In some embodiments, the hardware may take the form of a plurality of fasteners, such as a plurality of rivets.","The three dimensional structural frames 1120 and 1122 may take the form of or be similar in form to three dimensional structural frame 300 and/or three dimensional structural frame 600.With this arrangement, the variable cross section three dimensional structure of the three dimensional structural frames 1120 and 1122 may create a slope to the roof 1110 and help to shed water, other fluids, and debris from the roof 1100.In other examples, the three dimensional structural frames 1120 and 1122 may take the form of or be similar in form to three dimensional structural frames having a three dimensional structure with a constant cross section.","With this arrangement, the three dimensional structure of the three dimensional structural frames 1120 and 1122 may help to provide structural support for the roof 1100.In addition, in some embodiments, other components may be attached to three dimensional structural frames 1120 and 1122, including ceiling panels and insulation.","Further, as shown in FIG.","11a, the roof 1100 includes weatherproof membranes 1130A and 1130B overlaying plates secured to three dimensional structural frames (not shown).","The membranes 1130A and 1130B may be attached to wall panel portions of the wall sections, such as wall portion 910 of the wall section 900.For instance, the membranes 1130A and 1130B may be attached to wall panel portions of the walls sections by hardware, such as a plurality of fasteners.","In some such embodiments, the plurality of fasteners may be installed in through holes of the wall sections, such as through holes 1032A-1032D, and/or through holes of three dimensional structural frames, such as through holes 1012A-E. And in some such embodiments, the plurality of fasteners may comprise a plurality of rivets.","The weatherproof membranes 1130A and 1130B may help to reduce moisture from passing through the roof 1100.In addition, the weatherproof membranes 1130A and 1130B may help to insulate the roof 1100.Further still, as shown in FIG.","11a, the weatherproof membranes 1130A and 1130B may cover plates and three dimensional structural frames, except for connectors for fall protection harness 1170A, 1170B, and 1170C of the three dimensional structural frames.","The connectors 1170A, 1170B, and 1170C may take the form of or be similar in form to the connector 470 and/or the connector 770.The connectors 1170A, 1170B, and 1170C may improve safety of the roof 1100 and/or corresponding enclosure.","For instance, when maintenance is performed on the roof 1100 and/or corresponding enclosure, fall protection harness may be installed in the connectors 1170A, 1170B, and 1170C to provide fall protection.","FIG.","11b shows three dimensional structural frames 1180 connected to a strengthening member 1190, according to an example embodiment.","The enclosure 800 may further include a strengthening member that may take the form of or be similar in form to the strengthening member 1190.The strengthening member 1190 may tie each three dimensional structural frame of the three dimensional structural frames 1180 together.","In addition, the strengthening member 1190 may improve resistance of the three dimensional structural frames 1180 to torsion.","As shown in FIG.","11b, the three dimensional structural frames 1180 include twenty-two three dimensional structural frames 1180A-V.","However, in other examples, the three dimensional structural frames 1180 may include more or less than twenty-two three dimensional structural frames.","The number of three dimensional structural frames in the three dimensional structural frames 1180 may be selected based at least in part on a predetermined length and/or loading of an enclosure in the same or similar way as the number of three dimensional structural frames in the plurality of three dimensional structural frames 810 is selected.","Moreover, the three dimensional structural frames 1180A-V may take the form of any of the three dimensional structural frames described herein in the same or similar way as the structural frames 812, 814, 816, 818 of the plurality of structural frames 810.The strengthening member 1190 may take various different forms in various different embodiments.","In some embodiments, the strengthening member 1190 may comprise steel.","Moreover, in some embodiments, the strengthening member 1190 may be connected to a center of each three dimensional structural frame of the three dimensional structural frames 1180.FIG.","11b-1 shows aspects the three dimensional structural frames 1180 connected to the strengthening member 1190.As shown in FIG.","11b-1, in some embodiments, the strengthening member 1190 may have a U-shaped cross section.","And in some such embodiments, the strengthening member 1190 may be oriented, such that an open portion (not shown) of its cross section faces toward ground.","Other cross sectional shapes of the strengthening member are possible as well, including rectangular and triangular.","The thickness of the strengthening member 1190 may be selected based at least in part on a predetermined loading of the three dimensional structural frames 1180 and/or an enclosure (e.g., the thickness of the strengthening member 1190 may increase as the predetermined loading increases).","As shown in FIG.","11b, each three dimensional structural frame member of the three dimensional structural frame members 1180 connected to the strengthening member 1190 may be spaced apart from adjacent three dimensional structural frame members a certain distance (e.g., 1180A is spaced apart from 1180B a distance 1196).","In some embodiments, the distance between three dimensional structural frame members of the three dimensional structural frame members 1180 connected to the strengthening member 1190 may be substantially equal.","However, in some embodiments, the distance between a first set of adjacent three dimensional structural frame members of the three dimensional structural frame members 1180 connected to the strengthening member 1190 (e.g., 1180A and 1180B) may be different than a second set of adjacent three dimensional structural frame members of the three dimensional structural frame members 1180 connected to the strengthening member 1190 (e.g., 1180M and 1180N).","The distance between adjacent three dimensional structural frame members of the plurality of structural frame members 1180 connected to the strengthening member 1190 may have various different values.","For instance, in some embodiments, the distance between adjacent three dimensional structural frame members of the structural frame members 1180 connected to the strengthening member 1190 may be between 4 inches and 2 feet, such as 4 inches, 6 inches, one foot, and two feet.","The distance between adjacent three dimensional structural frame members of the structural frame members 1180 connected to the strengthening member 1190 may be based at least in part on a width of the three dimensional structural frame members 1180.In some such embodiments, the width of at least one three dimensional structural frame member of the three dimensional structural frame members 1180 may be 3 inches.","Moreover, in some such embodiments, when a three dimensional structural frame member comprises a support beam (e.g., support beam 360), the width of the three dimensional structural frame member may be 4 inches.","Further, as shown in FIG.","11b, beams 1192 and 1194 may be connected between three dimensional structural frame 11801 and three dimensional structural frame 1180J.","With this arrangement, beams 1192 and 1194 may define a penetration in a roof of an enclosure.","In some embodiments, an exhaust component may be installed in the penetration.","The beams 1192 and 1194 may take various different forms in various different embodiments.","For instance, in some embodiments, the beams 1192 and 1194 may comprise steel.","In addition, in some embodiments, the beams 1192 and 1194 may comprise C-channels.","Moreover, in some embodiments, the beams 1192 and 1194 may be flush with a web of the three dimensional structural frames 11801 and 1180J (e.g., web 342A).","Further, in some embodiments, the beams 1192 and 1194 may each be welded to the web of the three dimensional structural frames 11801 and 1180J.","The thickness of the beams 1192 and 1194 may be selected based at least in part on a predetermined loading of the three dimensional structural frames 1180 and/or an enclosure (e.g., the thickness of the beams 1192 and 1194 may increase as the predetermined loading increases).","FIG.","12a shows an enclosure 1200, according to an example embodiment.","The enclosure 1200 may include a plurality of three dimensional structural frames 1210, opposing wall portions 1220 interconnected by the plurality of three dimensional structural frames 1210, and a roof 1240 secured to at least some of the three dimensional structural frames of the plurality of three dimensional structural frames 1210.The opposing wall portions 1220 may include a plurality of wall sections 1230.In some embodiments, the roof 1240 may be secured to all of the three dimensional structural frames of the plurality of three dimensional structural frames 1210.With this arrangement, the roof 1240 may cover all of the three dimensional structural frames of the plurality of three dimensional structural frames 1210.Components of the enclosure 1200 of FIG.","12a may have the same arrangement and function in a similar manner as similarly numbered components of the enclosure 800 of FIG.","8.The enclosure 1200 may be used to surround equipment described herein.","In some embodiments, the enclosure 1200 may have a length of forty five feet.","Moreover, in some embodiments, the enclosure 1200 may be designed to withstand loads caused by wind that has a speed of 150 miles per hour.","Further, in some embodiments, the enclosure 1200 may be secured to a mounting surface 1290 shown in FIG.","12b.","Equipment may be located over the mounting surface 1290.And in some such embodiments, the plurality of wall sections 1230 may be secured to the mounting surface 1290 via through holes in bottom wall portions of the wall sections, such as through holes 946.Further, in some embodiments, the enclosure 1200 may be secured to a mounting plane.","D. Lift Plates FIG.","13 shows a lift plate 1300, according to an example embodiment.","The lift plate 1300 may engage the ends of a plurality of three dimensional structural frames, such as the plurality of three dimensional structural frames 810.The lift plate 1300 may include a planar portion 1310 comprising a series of a pattern of mounting holes 1312 for receiving hardware for securing the lift plate 1300 to the ends of the plurality of three dimensional structural frames and a connecting portion 1320 for engaging a harness that provides upward force to lift the plate and frames.","The series of a pattern of mounting holes 1312 may include a first series of a pattern of mounting holes 1314 and a second series of a pattern of mounting holes 1316.The connecting portion 1320 may include a hole 1322 for receiving the harness.","As shown in FIG.","13, the hole 1322 may be located through the connecting portion 1320.In some embodiments, the lift plate 1300 may be configured to be secured to two or more three dimensional structural frames, such as twelve three dimensional structural frames.","For instance, hardware may engage the first series of a pattern of mounting holes 1314 and through holes of the three dimensional structural frames, such as through holes 1012B and 1012C.","Moreover, in some embodiments, the lift plate 1300 may be configured to be secured to two or more wall sections, such as four wall sections.","For instance, hardware may engage the second series of a pattern of mounting holes 1316 and through holes of the wall sections, such as through holes 1032A-D.","In some embodiments, the hardware may include fasteners, such as bolts and rivet nuts.","The lift plate 1300 may comprise a variety of materials.","For instance, in some embodiments, the lift plate 1300 may comprise steel.","And in some such embodiments, the lift plate 1300 may comprise 5/16 inch hot rolled steel.","Moreover, in other embodiments, the lift plate 1300 may comprise steel having other thicknesses.","In some embodiments, a connecting portion of a lift plate may include a reinforcement plate.","FIG.","14a shows a lift plate 1400, according to an example embodiment.","The lift plate 1400 includes a connecting portion 1420 that includes a reinforcement plate 1424.The lift plate 1400 may engage the ends of a plurality of three dimensional structural frames, such as the plurality of three dimensional structural frames 810.The lift plate 1400 may include a planar portion 1410 comprising a series of a pattern of mounting holes 1412 for receiving hardware for securing the lift plate 1400 to the ends of the plurality of three dimensional structural frames and the connecting portion 1420 for engaging a harness that provides upward force to lift the plate and frames.","The series of a pattern of mounting holes 1412 may include a first series of a pattern of mounting holes 1414 and a second series of a pattern of mounting holes 1416.The connecting portion 1420 may include a hole 1422 for receiving the harness and the reinforcement plate 1424.As shown in FIG.","14a, the hole 1422 may be located through the connecting portion 1420 and the reinforcement plate 1424.FIG.","14b shows a perspective view of the lift plate 1400, according to an example embodiment.","In some embodiments, the hardware may include fasteners, such as bolts and rivet nuts.","Components of lift plate 1400 of FIG.","14a may have the same arrangement and function in a similar manner as similarly numbered components of the lift plate 1300 of FIG.","13.In addition, the lift plate 1400 may be secured to the ends of the plurality of three dimensional structural frames and wall sections in the same or similar way as the lift plate 1300 is secured to the ends of the plurality of three dimensional structural frames and wall sections.","In some embodiments, the reinforcement plate 1424 may be welded to the connecting portion 1420.And in some such embodiments, the reinforcement plate 1424 may be fillet welded to the connecting portion 1420.Moreover, the reinforcement plate 1424 may comprise a variety of materials.","For instance, in some embodiments, the reinforcement plate 1424 may comprise steel.","And in some such embodiments, the reinforcement plate 1424 may comprise the same or similar material as the planar portion 1410 and the connecting portion 1420.The reinforcement plate 1424 may strengthen the lift plate 1400, for example, by improving resistance of the lift plate 1400 to deformation, bending, rupturing, breaking, and other modes of failure.","Further, in some embodiments, the lift plate 1400 may have a second reinforcement plate 1426.FIG.","14c shows a side view of the lift plate 1400, according to an example embodiment.","As shown in FIG.","14c, the second reinforcement plate 1426 may be located opposite the reinforcement plate 1424.The second reinforcement plate 1426 may have the same arrangement and function in a similar manner as the reinforcement plate 1424.Moreover, the second reinforcement plate 1426 may be welded to the connecting portion 1420 in the same or similar way as the reinforcement plate 1424 is welded to the connecting portion 1420.The second reinforcement plate 1426 may strengthen the lift plate 1400 in the same or similar way as the reinforcement plate 1400 strengthens the lift plate 1400.E.","Liftable Enclosures FIG.","15a shows a liftable enclosure 1500, according to an example embodiment.","The liftable enclosure 1500 includes a plurality of the three dimensional structural frames 1510 and at least two lift plates 1520.The at least two lift plates 1520 may be used to lift the liftable enclosure 1500 with an upward force in a direction that is substantially parallel to a direction 1580.The term “substantially parallel,” as used in this disclosure, means exactly parallel or one or more deviations from exactly parallel that do not significantly impact lifting an enclosure as described herein.","In the illustrated example, a first three dimensional structural frame 1512A may be located at a first end of the liftable enclosure 1500 and a second three dimensional structural frame 1512B may be located at a second end of the liftable enclosure 1500.Numerous three dimensional structural frames may be located between the first three dimensional structural frame 1512A and the second three dimensional structural frame 1512B.","The three dimensional structural frames of the plurality of three dimensional structural frames 1510 may take the form of any of the three dimensional structural frames described herein.","Moreover, in the illustrated example, the at least two lift plates 1520 may include six lift plates 1522A-F.","However, in other examples, the at least two lift plates 1520 may include more or less six lift plates, such as two lift plates or eight lift plates.","In some embodiments, when the at least two lift plates 1520 include six lift plates, the liftable enclosure 1500 may have a length of forty five feet.","Moreover, in some embodiments, when the liftable enclosure 1500 has a length greater than forty five feet, the at least two lift plates 1520 may include more than six lift plates, such as eight lift plates.","Lift plates may be equally distributed on two sides of the liftable enclosure 1500.For example, as shown in FIG.","15a, when the at least two lift plates 1520 include six lift plates, three lift plates (1522A, 1522C, and 1522E) may be located on a first side of the liftable enclosure 1500, and three lift plates (1522B, 1522D, and 1522F) may be located on a second side of the liftable enclosure 1500.As shown in FIG.","15a-1, the lift plate 1522A includes a planar portion 1523A comprising a series of a pattern of mounting holes 1525A for receiving hardware for securing the plate to the ends of the plurality of three dimensional structural frames 1510 and a connecting portion 1524A for engaging a harness that provides an upward force to lift the lift plate 1522A and the three dimensional structural frames 1510.The series of a pattern of mounting holes 1525A may include a first series of a pattern of mounting holes 1526A and a second series of a pattern of mounting holes 1527A.","The connecting portion may further include a hole 1529A for receiving the harness and a reinforcement plate 1528B.","The hole 1529A may be through the connecting portion 1524 and the reinforcement plate 1528B.","The lift plates 1522B-F may take the form of or be similar in form to and function in a similar manner as the lift plate 1522A.","The planar portion 1523A may take the form of or be similar in form to the planar portion 1410, the connecting portion 1524A may take the form of or be similar in form to the connecting portion 1420, the series of a pattern of mounting holes 1525A may take the form of or be similar in form to the series of a pattern of mounting holes 1412, the first series of a pattern of mounting holes 1526A may take the form of or be similar in form to the first series of a pattern of mounting holes 1414, the second series of a pattern of mounting holes 1527A may take the form of or be similar in form to the second series of a pattern of mounting holes 1416, the reinforcement plate 1528A may take the form of or be similar in form the reinforcement plate 1424, and the hole 1529A may take the form of or be similar in form to the hole 1422.In some embodiments, the lift plate 1522A may be configured to be secured to two or more three dimensional structural frames, such as twelve three dimensional structural frames.","For instance, hardware may engage the first series of a pattern of mounting holes 1526A and through holes of the three dimensional structural frames, such as through holes 1012B and 1012C.","In some embodiments, the hardware may include fasteners, such as bolts and rivet nuts.","With this arrangement, one four-through-hole pattern of the first series of a pattern of mounting holes 1526A may correspond to through holes of a three dimensional structural frame, such as through holes 1012B and 1012C.","Lift plates 1522B-E may be configured to be secured to three dimensional structural frames in the same or similar way that the lift plate 1522A is configured to be secured to three dimensional structural frames.","Further, the liftable enclosure 1500 includes opposing walls 1530 interconnected by the plurality of three dimensional structural frames 1510, wherein the walls 1530 comprise a plurality of uniform wall sections 1540.In the illustrated example, wall section 1540A includes a wall panel portion 1542A, a top wall portion 1544A, and sidewall portions 1546A and 1548A.","With this arrangement, the sidewall portions of the plurality of wall sections 1540 are connected to form at least a portion of a wall of the enclosure 1500, where the plurality of three dimensional structural frames 1510 are attached to the top wall portions of the wall sections 1540.In some embodiments, the lift plates 1520 may be connected to the wall panel portions of the wall sections.","The wall panel portion 1542A may take the form of or be similar in form to the wall panel portion 910, the top wall portion 1544A may take the form of or be similar in form to the top wall portion 920, and sidewall portions 1546A and 1548A may take the form of or be similar in form to the sidewall portions 930A and 930B.","In some embodiments, the lift plate 1522A may be configured to be secured to two or more wall sections, such as four wall sections.","For instance, hardware may engage the second series of a pattern of mounting holes 1527A and through holes of the wall sections, such as through holes 1032A-D.","In some embodiments, the hardware may include fasteners, such as bolts and rivet nuts.","Further, in some embodiments, when the liftable enclosure 1500 includes a roof with a weatherproof membrane, such as the weatherproof membranes 1130A and 1130B, hardware may engage the series of pattern of mounting holes, through holes of the three dimensional structural frame members, and through holes of the wall sections after the weatherproof membrane is secured to the three dimensional structural frame members and walls sections.","And in some such embodiments, the weatherproof membrane is secured to the three dimensional structural frame members via the through holes of the three dimensional structural frame members and via the through holes of the wall sections.","Further still, in some embodiments, using the at least two lift plates 1520 to lift the liftable enclosure 1500 may reduce damage to the enclosure after or while the enclosure is lifted.","Moreover, in some embodiments, the enclosure 1500 may be designed to withstand loads caused by wind that has a speed of 150 miles per hour.","III.","Example Methods FIG.","16 shows a method 1600 for building an enclosure, according to an example embodiment.","Method 1600 begins at block 1602 with fabricating opposing walls of the enclosure by attaching sidewall portions of a plurality of wall sections comprising a wall panel portion, a top wall portion, and sidewall portions, wherein the sidewall portions of the plurality of wall portions are connected to form at least a portion of a wall of the enclosure.","The opposing walls may take the form of or be similar in form to the opposing walls 820, opposing walls 1220, and/or the opposing walls 1530; and the wall sections may each take the form of or be similar in form to the wall section 900.Method 1600 continues at block 1604 with attaching a plurality of three dimensional structural frames to the top wall portions of the wall sections of the opposing walls.","The plurality of three dimensional structural frames may take the form of or be similar in form to the plurality of three dimensional structural frames 810, the plurality of three dimensional structural frames 1210, and/or the plurality of three dimensional structural frames 1510.In some embodiments, the opposing walls are fabricated while the sidewall portions are substantially horizontal.","The term “substantially horizontal,” as used in this disclosure, means exactly horizontal or one or more deviations from exactly horizontal that do not significantly impact lifting enclosures described herein.","Moreover, in some embodiments, the opposing walls are uprighted by attaching a lift plate to a top end of a plurality of wall sections and lifting the top end.","The lift plate may take the form of or be similar in form to the lift plate 1300 and/or the lift plate 1400.FIG.","17 shows a method 1700 for lifting an enclosure, such as the enclosure 800 and/or the enclosure 1300, according to an example embodiment.","Method 1700 begins at block 1702 with attaching a plurality of lift plates to a plurality of the ends of the three dimensional structural frames and wall panels sections of the opposing walls.","Further, method 1700 continues at block 1704 with attaching a harness to the plurality of lift plates.","And method continues at block 1706 with lifting the enclosure with an upward force to the harness.","In some embodiments, the lift plates comprise (i) a planar portion comprising a series of a pattern of mounting holes for receiving hardware for securing the plate to the ends of the plurality of frames and the wall panel sections, and (ii) a connecting portion for attaching the harness.","The lift plates may take the form of or be similar in form to the lift plate 1300 and/or the lift plate 1400.Moreover, in some embodiments, the harness may be attached to the plurality of lift plates via a hole in the lift plates, such as the hole 1322 and/or the hole 1422.IV.","Conclusion Examples given above are merely illustrative and are not meant to be an exhaustive list of all possible embodiments, applications or modifications of the invention.","Thus, various modifications and variations of the described methods and systems of the invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention.","Although the invention has been described in connection with specific embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments.","Indeed, various modifications of the described modes for carrying out the invention which are obvious to the skilled artisan.","It is understood that the invention is not limited to the particular methodology, protocols, etc., described herein, as these may vary as the skilled artisan will recognize.","It is also to be understood that the terminology used herein is used for the purpose of describing particular embodiments only, and is not intended to limit the scope of the invention.","It also is to be noted that, as used herein and in the appended claims, the singular forms “a,” “an,” and “the” include the plural reference unless the context clearly dictates otherwise.","Thus, for example, a reference to “a three dimensional structural frame” is a reference to one or more three dimensional structural frames and equivalents thereof known to those skilled in the art.","Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art to which the invention pertains.","The embodiments of the invention and the various features and advantageous details thereof are explained more fully with reference to the non-limiting embodiments and/or illustrated in the accompanying drawings and detailed in the following description.","It should be noted that the features illustrated in the drawings are not necessarily drawn to scale, and features of one embodiment may be employed with other embodiments as the skilled artisan would recognize, even if not explicitly stated herein.","Any numerical values recited herein include all values from the lower value to the upper value in increments of one unit provided that there is a separation of at least two units between any lower value and any higher value.","As an example, if it is stated that the concentration of a component or value of a process variable such as, for example, size, angle size, pressure, time and the like, is, for example, from 1 to 90, specifically from 20 to 80, more specifically from 30 to 70, it is intended that values such as 15 to 85, 22 to 68, 43 to 51, 30 to 32, etc.","are expressly enumerated in this specification.","For values which are less than one, one unit is considered to be 0.0001, 0.001, 0.01 or 0.1 as appropriate.","These are only examples of what is specifically intended and all possible combinations of numerical values between the lowest value and the highest value enumerated are to be considered to be expressly stated in this application in a similar manner.","Particular methods, devices, and materials are described, although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the invention.","The disclosures of all references and publications cited above are expressly incorporated by reference in their entireties to the same extent as if each were incorporated by reference individually."]],"string":"[\n [\n \"Three Dimensional Structural Frames and Enclosures\",\n \"Three dimensional structural frames and enclosures and related methods are disclosed herein.\",\n \"In an example embodiment, an enclosure includes a plurality of three dimensional structural frames and opposing wall portions interconnected by the plurality of three dimensional structural frames, where the wall portions include a plurality of uniform wall sections, where the wall sections include a wall panel portion, a top wall portion, and sidewall portions, where the sidewall portions of the plurality of wall sections are joined to form the wall portions, and where the plurality of three dimensional structural frames are attached to the top wall portions of the wall sections.\"\n ],\n [\n \"1.An enclosure, comprising: (a) a plurality of three dimensional structural frames, wherein at least one three dimensional structural frame of the plurality of three dimensional structural frames comprises: two three dimensional structural frame members connected at their first ends, wherein each three dimensional structural frame member of the two three dimensional structural frame members comprises: a frame member comprising a variable cross section three dimensional structure comprising the first end, a second end, a first flange, a web, and a second flange, wherein the web extends from the first end to the second end, and wherein the web extends from the first flange to the second flange, a mounting flange at the second end of the variable cross section three dimensional structure that at least partially encloses the second end, wherein the mounting flange comprises through holes for mounting the frame member, and a transverse stiffener positioned within the variable cross section three dimensional structure comprising a rigid support structure rigidly fixed to the first flange, the web, and the second flange of the variable cross section three dimensional structure; and (b) opposing wall portions interconnected by the plurality of three dimensional structural frames, wherein the wall portions comprise a plurality of uniform wall sections, wherein the wall sections each comprise a wall panel portion, a top wall portion that extends from the wall panel portion, and sidewall portions that extend from the wall panel portion, wherein the sidewall portions of the plurality of wall sections are joined to form the wall portions, and wherein the plurality of three dimensional structural frames are attached to the top wall portions of the wall sections.\",\n \"2.The enclosure of claim 1, wherein the at least one three dimensional structural frame of the plurality of three dimensional structural frames further comprises a connector for a fall protection harness sandwiched between the first ends of the two three dimensional structural frame members, wherein the connector comprises a first surface and a second surface opposite the first surface, wherein a first portion of the first surface contacts the first end of one of the two three dimensional structural frame members, wherein a first portion of the second surface contacts the first end of the other three dimensional structural frame member, and wherein a second portion of the first surface and a second portion of the second surface each extend above each second flange of the two three dimensional structural frame members.\",\n \"3.The enclosure of claim 1, wherein the wall sections each further comprise a bottom wall portion that extends from the wall panel portion.\",\n \"4.The enclosure of claim 1, wherein the sidewalls of the plurality of wall sections are connected by a plurality of rivets, wherein the enclosure further comprises a gasket between at least two sidewall portions of the sidewall portions, and wherein the gasket comprises a silicone bead, polyurethane, or structural adhesive.\",\n \"5.The enclosure of claim 1, further comprising: a roof comprising a plate secured to at least one three dimensional structural frame of the three dimensional structural frames and an overlaying weatherproof membrane, wherein the plate comprises sheet metal, and wherein the overlaying weatherproof membrane is attached to the wall panel portions of the wall sections.\",\n \"6.The enclosure of claim 1, further comprising a strengthening member connected to at least some three dimensional structural frames of the plurality of three dimensional structural frames; and a lift plate for engaging the ends of the plurality of three dimensional structural frames, wherein the lift plate comprises (a) a planar portion comprising a series of a pattern of mounting holes for receiving hardware for securing the plate to the ends of the plurality of frames, and (b) a connecting portion for engaging a harness that provides upward force to lift the plate and the frames, wherein the connecting portion comprises two reinforcement plates.\",\n \"7.A method for lifting the enclosure of claim 1, comprising: (a) attaching a plurality of lift plates to at least some second ends of the three dimensional structural frames and at least some of the wall panel sections of the opposing walls, wherein a first lift plate of the plurality of lift plates is secured to two or more frames of the three dimensional structural frames, and wherein a second lift plate of the plurality of lift plates is secured to two or more other frames of the three dimensional structural frames, and wherein the first lift plate is secured to two or more wall panel sections of the opposing walls, and the second lift plate is secured to two or more other wall panel sections of the opposing walls; (b) attaching a harness to the plurality of lift plates; and (c) lifting the enclosure with an upward force to the harness, wherein the first lift plate and the second lift plate each comprises (i) a planar portion comprising a series of a pattern of mounting holes for receiving hardware for securing the plate to the ends of the plurality of frames and the wall panel sections; and (ii) a connecting portion for attaching the harness.\",\n \"8.An enclosure, comprising: (a) a plurality of three dimensional structural frames, wherein at least one three dimensional structural frame of the plurality of three dimensional structural frames comprises: two three dimensional structural frame members connected at their first ends, wherein each three dimensional structural frame member of the two three dimensional structural frame members comprises: a frame member comprising a three dimensional structure comprising the first end, a second end, a first flange, a web, and a second flange, wherein the first end has a first width, the second end has a second width, and the first and second widths are substantially equal, wherein the web extends from the first end to the second end, and wherein the web extends from the first flange to the second flange, a mounting flange at the second end of the three dimensional structure that at least partially encloses the second end, wherein the mounting flange comprises through holes for mounting the frame member, and a transverse stiffener positioned within the three dimensional structure comprising a rigid support structure rigidly fixed to the first flange, the web, and the second flange of the three dimensional structure; and (b) opposing wall portions interconnected by the plurality of three dimensional structural frames, wherein the wall portions comprise a plurality of uniform wall sections, wherein the wall sections each comprise a wall panel portion, a top wall portion that extends from the wall panel portion, and sidewall portions that extend from the wall panel portion, wherein the sidewall portions of the plurality of wall sections are joined to form the wall portions, and wherein the plurality of three dimensional structural frames are attached to the top wall portions of the wall sections.\",\n \"9.The enclosure of claim 8, wherein the at least one three dimensional structural frame of the plurality of three dimensional structural frames further comprises a connector for a fall protection harness sandwiched between the first ends of the two three dimensional structural frame members, wherein the connector comprises a first surface and a second surface opposite the first surface, wherein a first portion of the first surface contacts the first end of one of the two three dimensional structural frame members, wherein a first portion of the second surface contacts the first end of the other three dimensional structural frame member, and wherein a second portion of the first surface and a second portion of the second surface each extend above each second flange of the two three dimensional structural frame members.\",\n \"10.The enclosure of claim 8, wherein the wall sections each further comprise a bottom wall portion that extends from the wall panel portion.\",\n \"11.The enclosure of claim 8, wherein the sidewalls of the plurality of wall sections are connected by a plurality of rivets, wherein the enclosure further comprises a gasket between at least two sidewall portions of the sidewall portions, and wherein the gasket comprises a silicone bead, polyurethane, or structural adhesive.\",\n \"12.The enclosure of claim 8, further comprising: a roof comprising a plate secured to at least one three dimensional structural frame of the three dimensional structural frames and an overlaying weatherproof membrane, wherein the plate comprises sheet metal, and wherein the overlaying weatherproof membrane is attached to the wall panel portions of the wall sections.\",\n \"13.The enclosure of claim 8, further comprising a strengthening member connected to at least some three dimensional structural frames of the plurality of three dimensional structural frames; and a lift plate for engaging the ends of the plurality of three dimensional structural frames, wherein the lift plate comprises (a) a planar portion comprising a series of a pattern of mounting holes for receiving hardware for securing the plate to the ends of the plurality of frames, and (b) a connecting portion for engaging a harness that provides upward force to lift the plate and the frames, wherein the connecting portion comprises two reinforcement plates.\",\n \"14.A method for lifting the enclosure of claim 8, comprising: (a) attaching a plurality of lift plates to at least some second ends of the three dimensional structural frames and at least some of the wall panel sections of the opposing walls, wherein a first lift plate of the plurality of lift plates is secured to two or more frames of the three dimensional structural frames, and wherein a second lift plate of the plurality of lift plates is secured to two or more other frames of the three dimensional structural frames, and wherein the first lift plate is secured to two or more wall panel sections of the opposing walls, and the second lift plate is secured to two or more other wall panel sections of the opposing walls; (b) attaching a harness to the plurality of lift plates; and (c) lifting the enclosure with an upward force to the harness, wherein the first lift plate and the second lift plate each comprises (i) a planar portion comprising a series of a pattern of mounting holes for receiving hardware for securing the plate to the ends of the plurality of frames and the wall panel sections; and (ii) a connecting portion for attaching the harness.\",\n \"15.An enclosure, comprising: (a) a plurality of three dimensional structural frames, wherein at least one three dimensional structural frame of the plurality of three dimensional structural frames comprises: a frame member comprising an elongated three dimensional structure having a first side, a second side, a center support portion, a first flange, a web, and a second flange, wherein the first side has a variable cross section from a first end to the center support portion, wherein the second side has a variable cross section from a second end to the center support portion, wherein the web extends from the first end to the second end, and wherein the web extends from the first flange to the second flange, the frame member further comprising mounting flanges at the first end and the second end that at least partially enclose the first end and the second end, wherein the mounting flanges comprise through holes for mounting the frame member, and transverse stiffeners positioned within the three dimensional structure on the first side and the second side comprising a rigid support structure rigidly fixed to the first flange, the web, and the second flange of the three dimensional structure, wherein the transverse stiffeners are welded to the first flange, the web, and the second flange of the elongated three dimensional structure; and (b) opposing wall portions interconnected by the plurality of three dimensional structural frames, wherein the wall portions comprise a plurality of uniform wall sections, wherein the wall sections each comprise a wall panel portion, a top wall portion that extends from the wall panel portion, and sidewall portions that extend from the wall panel portion, wherein the sidewall portions of the plurality of wall sections are joined to form the wall portions, and wherein the plurality of three dimensional structural frames are attached to the top wall portions of the wall sections.\",\n \"16.The enclosure of claim 15, wherein the at least one three dimensional structural frame of the plurality of three dimensional structural frames further comprises a center support mounted at the center support portion, wherein the center support comprises a connector for a fall protection harness, wherein the connector comprises a first surface and a second surface opposite the first surface, wherein the first surface faces the first end, wherein the second surface faces the second end, such that the first surface and the second surface are each perpendicular to an axis that extends between the first end and the second end, wherein a first portion of the first surface and a first portion of the second surface each contact the second flange, and wherein a second portion of the first surface and a second portion of the second surface each extend above the second flange.\",\n \"17.The enclosure of claim 15, wherein the wall sections each further comprise a bottom wall portion that extends from the wall panel portion.\",\n \"18.The enclosure of claim 15, wherein the sidewalls of the plurality of wall sections are connected by a plurality of rivets, wherein the enclosure further comprises a gasket between at least two sidewall portions of the sidewall portions, and wherein the gasket comprises a silicone bead, polyurethane, or structural adhesive.\",\n \"19.The enclosure of claim 15, further comprising: a roof comprising a plate secured to at least one three dimensional structural frame of the three dimensional structural frames and an overlaying weatherproof membrane, wherein the plate comprises sheet metal, and wherein the overlaying weatherproof membrane is attached to the wall panel portions of the wall sections.\",\n \"20.The enclosure of claim 15, further comprising a strengthening member connected to at least some three dimensional structural frames of the plurality of three dimensional structural frames; and a lift plate for engaging the ends of the plurality of three dimensional structural frames, wherein the lift plate comprises (a) a planar portion comprising a series of a pattern of mounting holes for receiving hardware for securing the plate to the ends of the plurality of frames, and (b) a connecting portion for engaging a harness that provides upward force to lift the plate and the frames, wherein the connecting portion comprises two reinforcement plates.\",\n \"21.A method for lifting the enclosure of claim 15, comprising: (a) attaching a plurality of lift plates to at least some second ends of the three dimensional structural frames and at least some of the wall panel sections of the opposing walls, wherein a first lift plate of the plurality of lift plates is secured to two or more frames of the three dimensional structural frames, and wherein a second lift plate of the plurality of lift plates is secured to two or more other frames of the three dimensional structural frames, and wherein the first lift plate is secured to two or more wall panel sections of the opposing walls, and the second lift plate is secured to two or more other wall panel sections of the opposing walls; (b) attaching a harness to the plurality of lift plates; and (c) lifting the enclosure with an upward force to the harness, wherein the first lift plate and the second lift plate each comprises (i) a planar portion comprising a series of a pattern of mounting holes for receiving hardware for securing the plate to the ends of the plurality of frames and the wall panel sections; and (ii) a connecting portion for attaching the harness.\"\n ],\n [\n \" BACKGROUND Enclosures may be used to surround equipment located outside of a building in an industrial facility or equipment located inside of a building.\",\n \"Such enclosures may protect the equipment from a variety of environmental conditions, such as extreme temperatures, humidity, and moisture.\"\n ],\n [\n \" SUMMARY In one aspect, a three dimensional structural member is disclosed.\",\n \"The three dimensional structural member includes a frame member that includes a variable cross section three dimensional structure that includes a first end and a second end; a mounting flange at the second end of the variable cross section three dimensional structure that at least partially encloses the second end, where the mounting flange includes through holes for mounting the frame member; and a transverse stiffener positioned within the variable cross section three dimensional structure that includes a rigid support structure rigidly fixed to a first flange, a web, and a second flange of the variable cross section three dimensional structure.\",\n \"In another aspect, a three dimensional structural frame member is disclosed, where the variable cross section three dimensional structure is a single piece of sheet metal.\",\n \"In another aspect, a three dimensional structural frame member is disclosed, where the variable cross section three dimensional structure and the mounting flange include a single piece of sheet metal.\",\n \"In another aspect, a three dimensional structural frame member is disclosed, where the variable cross section three dimensional structure is an open three dimensional structure.\",\n \"In another aspect, a three dimensional structural frame member is disclose, where the transverse stiffener is welded to the first flange, the web, and the second flange of the variable cross section three dimensional structure.\",\n \"In another aspect, a three dimensional structural frame is disclosed.\",\n \"The three dimensional structural frame includes two three dimensional structural frame members connected at their first ends.\",\n \"In another aspect, a three dimensional structural frame is disclosed, further including a connector for a fall protection harness between the firsts ends of the two three dimensional structural frame members.\",\n \"In another aspect, a three dimensional structural frame member is disclosed.\",\n \"The three dimensional structural frame member includes a frame member that includes a three dimensional structure that includes a first end and a second end, where the first end has a first width, the second end has a second width, and the first and second widths are substantially equal; a mounting flange at the second end of the three dimensional structure that at least partially encloses the second end, where the mounting flange includes through holes for mounting the frame member; and a transverse stiffener positioned within the three dimensional structure that includes a rigid support structure rigidly fixed to a first flange, a web, and a second flange of the three dimensional structure.\",\n \"In another aspect, a three dimensional structural frame is disclosed, where the three dimensional structure is a single piece of sheet metal.\",\n \"In another aspect, a three dimensional structural frame is disclosed, where the three dimensional structure and the mounting flange include a single piece of sheet metal.\",\n \"In another aspect, a three dimensional structural frame is disclosed, where the three dimensional structure is an open three dimensional structure.\",\n \"In another aspect, a three dimensional structural frame is disclosed, where the transverse stiffener is welded to the first flange, the web, and the second flange of the three dimensional structure.\",\n \"In another aspect, a three dimensional structural frame is disclosed.\",\n \"The three dimensional structural frame includes two three dimensional structural frames connected at their first ends.\",\n \"In another aspect, a three dimensional structural frame is disclosed, further including a connector for a fall protection harness between the firsts ends of the two three dimensional structural frame members.\",\n \"In another aspect, a three dimensional structural frame is disclosed.\",\n \"The three dimensional structural frame includes a frame member that includes an elongated three dimensional structure having a first side, a second side, and a center support portion, where the first side has a variable cross section from a first end to the center support portion, and where the second side has a variable cross section from a second end to the center support portion, the frame member further includes mounting flanges at the first end and the second end that at least partially enclose the first end and the second end, where the mounting flanges include through holes for mounting the frame member; a center support mounted at the center support portion; and transverse stiffeners positioned within the three dimensional structure on the first side and the second side that includes a rigid support structure rigidly fixed to a first flange, a web, and a second flange of the three dimensional structure.\",\n \"In another aspect, a three dimensional structural frame is disclosed, where the frame member is a single piece of sheet metal.\",\n \"In another aspect, a three dimensional structural frame is disclosed, where the center support includes a connector for a fall protection harness.\",\n \"In another aspect, a three dimensional structural frame is disclosed, where the transverse stiffeners are welded to the first flange, the web, and the second flange of the three dimensional structure.\",\n \"In another aspect, an enclosure is disclosed.\",\n \"The enclosure includes a plurality of three dimensional structural frames; and opposing wall portions interconnected by the plurality of three dimensional structural frames, where the wall portions include a plurality of uniform wall sections, where the wall sections include a wall panel portion, a top wall portion, and sidewall portions, where the sidewall portions of the plurality of wall sections are joined to form the wall portions, where the plurality of three dimensional structural frames are attached to the top wall portions of the wall sections.\",\n \"In another aspect, an enclosure is disclosed, where the ends of the three dimensional structural frames overlap and are simultaneously attached to two wall sections.\",\n \"In another aspect, an enclosure is disclosed, where the wall sections include a single piece of formed sheet metal.\",\n \"In another aspect, an enclosure is disclosed, further including a plurality of support members, where the support members extend between the opposing wall portions.\",\n \"In another aspect, an enclosure is disclosed, where the wall sections include a bottom wall portion.\",\n \"In another aspect, an enclosure is disclosed, where the sidewalls of the plurality of wall sections are connected by a plurality of rivets.\",\n \"In another aspect, an enclosure is disclosed, further including a gasket between the sidewall portions.\",\n \"In another aspect, an enclosure is disclosed, where the gasket includes a silicone bead, polyurethane, or structural adhesive.\",\n \"In another aspect, an enclosure is disclosed, further including a roof that includes a plate secured to the three dimensional structural frames.\",\n \"In another aspect, an enclosure is disclosed, where the plate includes sheet metal.\",\n \"In another aspect, an enclosure is disclosed, where the plate includes perforated sheet metal.\",\n \"In another aspect, an enclosure is disclosed, where the roof further includes a weatherproof membrane overlaying the plate and attached to the wall panel portions of the wall sections.\",\n \"In another aspect, an enclosure is disclosed, further including a first support member connected to a first group of wall sections, and a second support member connected to a second group of wall sections.\",\n \"In another aspect, an enclosure disclosed, further including a strengthening member connected to the plurality of three dimensional structural frames.\",\n \"In another aspect, a lift plate for engaging the ends of a plurality of three dimensional structural frames is disclosed.\",\n \"The lift plate includes a planar portion that includes a series of a pattern of mounting holes for receiving hardware for securing the plate to the ends of the plurality of frames; and a connecting portion for engaging a harness that provides upward force to lift the plate and the frames.\",\n \"In another aspect, a lift plate is disclosed, where the connecting portion includes a reinforcement plate.\",\n \"In another aspect, a lift plate is disclosed, where the connecting portion includes two reinforcement plates.\",\n \"In another aspect, a liftable enclosure is disclosed.\",\n \"The liftable enclosure includes a plurality of the three dimensional structural frames; and at least two lift plates that include a planar portion that includes a series of a pattern of mounting holes for receiving hardware for securing the plate to the ends of the plurality of frames and a connecting portion for engaging a harness that provides an upward force to lift the plate and the frames.\",\n \"In another aspect, a liftable enclosure is disclosed, further including opposing walls interconnected by the plurality of three dimensional structural frames, where the walls include a plurality of uniform wall sections, where the wall sections include a wall panel portion, a top wall portion, and sidewall portions, where the sidewall portions of the plurality of wall sections are connected to form at least a portion of a wall of the enclosure, where the plurality of three dimensional structural frames are attached to the top wall portions of the wall sections.\",\n \"In another aspect, a liftable enclosure is disclosed, where the lift plates are further connected to the wall panel portions of the wall sections.\",\n \"In another aspect, a method for building a structure is disclosed.\",\n \"The method includes fabricating opposing walls of the structure by attaching sidewall portions of a plurality of wall sections comprising a wall panel portion, a top wall portion, and sidewall portions, where the sidewall portions of the plurality of wall sections; and attaching a plurality of three dimensional structural frames to the top walls portions of the wall sections of the opposing walls.\",\n \"In another aspect, a method is disclosed, where the opposing walls are fabricated while the sidewall portions are substantially horizontal.\",\n \"In another aspect, a method is disclosed, where the opposing walls are uprighted by attaching a lift plate to a top end of a plurality of wall sections and lifting the top end.\",\n \"In another aspect, a method for lifting an enclosure is disclosed.\",\n \"The method includes attaching a plurality of lift plates to the a plurality of the ends of the three dimensional structural frames and the wall panel sections of the opposing walls; attaching a harness to the plurality of lift plates; and lifting the structure with an upward force to the harness, where the lift plates include a planar portion that includes a series of a pattern of mounting holes for receiving hardware for securing the plate to the ends of the plurality of frames and the wall panel sections, and a connecting portion for attaching the harness.\"\n ],\n [\n \"CROSS REFERENCE TO RELATED APPLICATIONS The present application is a continuation of U.S. application Ser.\",\n \"No.\",\n \"14/818,046, filed Aug. 4, 2015, entitled “Three Dimensional Structural Frames and Enclosures,” which claims priority to U.S.\",\n \"Provisional Application No.\",\n \"62/160,556, filed May 12, 2015, entitled “Three Dimensional Structural Frames and Enclosures.” The entire disclosure contents of U.S. application Ser.\",\n \"No.\",\n \"14/818,046 and U.S.\",\n \"Provisional Application No.\",\n \"62/160,556 are herewith incorporated by reference into the present application.\",\n \"BACKGROUND Enclosures may be used to surround equipment located outside of a building in an industrial facility or equipment located inside of a building.\",\n \"Such enclosures may protect the equipment from a variety of environmental conditions, such as extreme temperatures, humidity, and moisture.\",\n \"SUMMARY In one aspect, a three dimensional structural member is disclosed.\",\n \"The three dimensional structural member includes a frame member that includes a variable cross section three dimensional structure that includes a first end and a second end; a mounting flange at the second end of the variable cross section three dimensional structure that at least partially encloses the second end, where the mounting flange includes through holes for mounting the frame member; and a transverse stiffener positioned within the variable cross section three dimensional structure that includes a rigid support structure rigidly fixed to a first flange, a web, and a second flange of the variable cross section three dimensional structure.\",\n \"In another aspect, a three dimensional structural frame member is disclosed, where the variable cross section three dimensional structure is a single piece of sheet metal.\",\n \"In another aspect, a three dimensional structural frame member is disclosed, where the variable cross section three dimensional structure and the mounting flange include a single piece of sheet metal.\",\n \"In another aspect, a three dimensional structural frame member is disclosed, where the variable cross section three dimensional structure is an open three dimensional structure.\",\n \"In another aspect, a three dimensional structural frame member is disclose, where the transverse stiffener is welded to the first flange, the web, and the second flange of the variable cross section three dimensional structure.\",\n \"In another aspect, a three dimensional structural frame is disclosed.\",\n \"The three dimensional structural frame includes two three dimensional structural frame members connected at their first ends.\",\n \"In another aspect, a three dimensional structural frame is disclosed, further including a connector for a fall protection harness between the firsts ends of the two three dimensional structural frame members.\",\n \"In another aspect, a three dimensional structural frame member is disclosed.\",\n \"The three dimensional structural frame member includes a frame member that includes a three dimensional structure that includes a first end and a second end, where the first end has a first width, the second end has a second width, and the first and second widths are substantially equal; a mounting flange at the second end of the three dimensional structure that at least partially encloses the second end, where the mounting flange includes through holes for mounting the frame member; and a transverse stiffener positioned within the three dimensional structure that includes a rigid support structure rigidly fixed to a first flange, a web, and a second flange of the three dimensional structure.\",\n \"In another aspect, a three dimensional structural frame is disclosed, where the three dimensional structure is a single piece of sheet metal.\",\n \"In another aspect, a three dimensional structural frame is disclosed, where the three dimensional structure and the mounting flange include a single piece of sheet metal.\",\n \"In another aspect, a three dimensional structural frame is disclosed, where the three dimensional structure is an open three dimensional structure.\",\n \"In another aspect, a three dimensional structural frame is disclosed, where the transverse stiffener is welded to the first flange, the web, and the second flange of the three dimensional structure.\",\n \"In another aspect, a three dimensional structural frame is disclosed.\",\n \"The three dimensional structural frame includes two three dimensional structural frames connected at their first ends.\",\n \"In another aspect, a three dimensional structural frame is disclosed, further including a connector for a fall protection harness between the firsts ends of the two three dimensional structural frame members.\",\n \"In another aspect, a three dimensional structural frame is disclosed.\",\n \"The three dimensional structural frame includes a frame member that includes an elongated three dimensional structure having a first side, a second side, and a center support portion, where the first side has a variable cross section from a first end to the center support portion, and where the second side has a variable cross section from a second end to the center support portion, the frame member further includes mounting flanges at the first end and the second end that at least partially enclose the first end and the second end, where the mounting flanges include through holes for mounting the frame member; a center support mounted at the center support portion; and transverse stiffeners positioned within the three dimensional structure on the first side and the second side that includes a rigid support structure rigidly fixed to a first flange, a web, and a second flange of the three dimensional structure.\",\n \"In another aspect, a three dimensional structural frame is disclosed, where the frame member is a single piece of sheet metal.\",\n \"In another aspect, a three dimensional structural frame is disclosed, where the center support includes a connector for a fall protection harness.\",\n \"In another aspect, a three dimensional structural frame is disclosed, where the transverse stiffeners are welded to the first flange, the web, and the second flange of the three dimensional structure.\",\n \"In another aspect, an enclosure is disclosed.\",\n \"The enclosure includes a plurality of three dimensional structural frames; and opposing wall portions interconnected by the plurality of three dimensional structural frames, where the wall portions include a plurality of uniform wall sections, where the wall sections include a wall panel portion, a top wall portion, and sidewall portions, where the sidewall portions of the plurality of wall sections are joined to form the wall portions, where the plurality of three dimensional structural frames are attached to the top wall portions of the wall sections.\",\n \"In another aspect, an enclosure is disclosed, where the ends of the three dimensional structural frames overlap and are simultaneously attached to two wall sections.\",\n \"In another aspect, an enclosure is disclosed, where the wall sections include a single piece of formed sheet metal.\",\n \"In another aspect, an enclosure is disclosed, further including a plurality of support members, where the support members extend between the opposing wall portions.\",\n \"In another aspect, an enclosure is disclosed, where the wall sections include a bottom wall portion.\",\n \"In another aspect, an enclosure is disclosed, where the sidewalls of the plurality of wall sections are connected by a plurality of rivets.\",\n \"In another aspect, an enclosure is disclosed, further including a gasket between the sidewall portions.\",\n \"In another aspect, an enclosure is disclosed, where the gasket includes a silicone bead, polyurethane, or structural adhesive.\",\n \"In another aspect, an enclosure is disclosed, further including a roof that includes a plate secured to the three dimensional structural frames.\",\n \"In another aspect, an enclosure is disclosed, where the plate includes sheet metal.\",\n \"In another aspect, an enclosure is disclosed, where the plate includes perforated sheet metal.\",\n \"In another aspect, an enclosure is disclosed, where the roof further includes a weatherproof membrane overlaying the plate and attached to the wall panel portions of the wall sections.\",\n \"In another aspect, an enclosure is disclosed, further including a first support member connected to a first group of wall sections, and a second support member connected to a second group of wall sections.\",\n \"In another aspect, an enclosure disclosed, further including a strengthening member connected to the plurality of three dimensional structural frames.\",\n \"In another aspect, a lift plate for engaging the ends of a plurality of three dimensional structural frames is disclosed.\",\n \"The lift plate includes a planar portion that includes a series of a pattern of mounting holes for receiving hardware for securing the plate to the ends of the plurality of frames; and a connecting portion for engaging a harness that provides upward force to lift the plate and the frames.\",\n \"In another aspect, a lift plate is disclosed, where the connecting portion includes a reinforcement plate.\",\n \"In another aspect, a lift plate is disclosed, where the connecting portion includes two reinforcement plates.\",\n \"In another aspect, a liftable enclosure is disclosed.\",\n \"The liftable enclosure includes a plurality of the three dimensional structural frames; and at least two lift plates that include a planar portion that includes a series of a pattern of mounting holes for receiving hardware for securing the plate to the ends of the plurality of frames and a connecting portion for engaging a harness that provides an upward force to lift the plate and the frames.\",\n \"In another aspect, a liftable enclosure is disclosed, further including opposing walls interconnected by the plurality of three dimensional structural frames, where the walls include a plurality of uniform wall sections, where the wall sections include a wall panel portion, a top wall portion, and sidewall portions, where the sidewall portions of the plurality of wall sections are connected to form at least a portion of a wall of the enclosure, where the plurality of three dimensional structural frames are attached to the top wall portions of the wall sections.\",\n \"In another aspect, a liftable enclosure is disclosed, where the lift plates are further connected to the wall panel portions of the wall sections.\",\n \"In another aspect, a method for building a structure is disclosed.\",\n \"The method includes fabricating opposing walls of the structure by attaching sidewall portions of a plurality of wall sections comprising a wall panel portion, a top wall portion, and sidewall portions, where the sidewall portions of the plurality of wall sections; and attaching a plurality of three dimensional structural frames to the top walls portions of the wall sections of the opposing walls.\",\n \"In another aspect, a method is disclosed, where the opposing walls are fabricated while the sidewall portions are substantially horizontal.\",\n \"In another aspect, a method is disclosed, where the opposing walls are uprighted by attaching a lift plate to a top end of a plurality of wall sections and lifting the top end.\",\n \"In another aspect, a method for lifting an enclosure is disclosed.\",\n \"The method includes attaching a plurality of lift plates to the a plurality of the ends of the three dimensional structural frames and the wall panel sections of the opposing walls; attaching a harness to the plurality of lift plates; and lifting the structure with an upward force to the harness, where the lift plates include a planar portion that includes a series of a pattern of mounting holes for receiving hardware for securing the plate to the ends of the plurality of frames and the wall panel sections, and a connecting portion for attaching the harness.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings, which are included to provide a further understanding of the disclosure, are incorporated in and constitute a part of this specification, illustrate embodiments of the disclosure, and together with the detailed description serve to explain the principles of the invention.\",\n \"No attempt is made to show structural details of the invention in more detail than may be necessary for a fundamental understanding of the invention and various ways in which it may be practiced.\",\n \"FIG.\",\n \"1 shows a three dimensional structural frame member, according to an example embodiment.\",\n \"FIG.\",\n \"1-1 shows aspects of the three dimensional structural frame member depicted in FIG.\",\n \"1, according to an example embodiment.\",\n \"FIG.\",\n \"2 shows aspects of a three dimensional structural frame member, according to an example embodiment.\",\n \"FIG.\",\n \"3a shows a three dimensional structural frame, according to an example embodiment.\",\n \"FIG.\",\n \"3a-1 shows aspects of the three dimensional structural frame depicted in FIG.\",\n \"3a, according to an example embodiment.\",\n \"FIG.\",\n \"3b shows a back view of the three dimensional structural frame depicted in FIG.\",\n \"3a, according to an example embodiment.\",\n \"FIG.\",\n \"3c shows a top view of the three dimensional structural frame depicted in FIG.\",\n \"3a, according to an example embodiment.\",\n \"FIG.\",\n \"3d shows a front view of the three dimensional structural frame depicted in FIG.\",\n \"3a, according to an example embodiment.\",\n \"FIG.\",\n \"4 shows a three dimensional structural frame, according to an example embodiment.\",\n \"FIG.\",\n \"4-1 shows aspects of the three dimensional structural frame depicted in FIG.\",\n \"4, according to an example embodiment.\",\n \"FIG.\",\n \"5 shows a three dimensional structural frame, according to an example embodiment.\",\n \"FIG.\",\n \"6 shows a three dimensional structural frame, according to an example embodiment.\",\n \"FIG.\",\n \"7 shows a three dimensional structural frame, according to an example embodiment.\",\n \"FIG.\",\n \"8 shows an enclosure, according to an example embodiment.\",\n \"FIG.\",\n \"9 shows a wall section, according to an example embodiment.\",\n \"FIG.\",\n \"9-1 shows aspects of the wall section depicted in FIG.\",\n \"9, according to an example embodiment.\",\n \"FIG.\",\n \"10a shows three dimensional structural frames connected to wall sections, according to an example embodiment.\",\n \"FIG.\",\n \"10b shows wall sections connected to a support member, according to an example embodiment.\",\n \"FIG.\",\n \"10c shows a side view of the plurality of wall sections connected to the support member depicted in FIG.\",\n \"10b, according to an example embodiment.\",\n \"FIG.\",\n \"10c-1 shows aspects of the sections connected to the support member depicted in FIG.\",\n \"10c, according to an example embodiment.\",\n \"FIG.\",\n \"11a shows aspects of a roof of an enclosure, according to an example embodiment.\",\n \"FIG.\",\n \"11b shows three dimensional structural frames connected to a strengthening member, according to an example embodiment.\",\n \"FIG.\",\n \"11b-1 shows aspects of the three dimensional structural frames connected to a strengthening member depicted in FIG.\",\n \"11b, according to an example embodiment.\",\n \"FIG.\",\n \"12a shows an enclosure, according to an example embodiment.\",\n \"FIG.\",\n \"12b shows a mounting surface, according to an example embodiment.\",\n \"FIG.\",\n \"13 shows a lift plate, according to an example embodiment.\",\n \"FIG.\",\n \"14a shows a lift plate, according to an example embodiment.\",\n \"FIG.\",\n \"14b shows a perspective view of the lift plate shown in FIG.\",\n \"14a, according to an example embodiment.\",\n \"FIG.\",\n \"14c shows a side view of the lift plate shown in FIG.\",\n \"14a, according to an example embodiment.\",\n \"FIG.\",\n \"15a shows a liftable enclosure, according to an example embodiment.\",\n \"FIG.\",\n \"15a-1 shows aspects of the liftable enclosure shown in FIG.\",\n \"15a, according to an example embodiment.\",\n \"FIG.\",\n \"16 shows a method for building a structure, according to an example embodiment.\",\n \"FIG.\",\n \"17 shows a method for lifting an enclosure, according to an example embodiment.\",\n \"DESCRIPTION I.\",\n \"Introduction It may be desirable to lift enclosures in a variety of situations.\",\n \"As one example, when an enclosure surrounds equipment (e.g., a generator, related electrical, electronic, and mechanical components, and a fuel tank) it may be desirable to lift the enclosure to access the equipment for repair or replacement.\",\n \"As another example, it may be desirable to lift an enclosure during installation or fabrication of the enclosure.\",\n \"In its various aspects, the disclosure is directed to three dimensional structural frames and enclosures and related methods.\",\n \"In an example embodiment, an enclosure may include three dimensional structural frames and opposing walls interconnected by the three dimensional structural frames, and lift plates may be connected to the three dimensional structural frames.\",\n \"The lift plates may be used to lift the enclosure upward.\",\n \"With this arrangement, the enclosure may be lifted without partially disassembling the enclosure.\",\n \"Beneficially, embodiments described herein may reduce labor, equipment, and/or time needed to lift enclosures.\",\n \"In addition, embodiments described herein may reduce damage to the enclosure after or while the enclosure is lifted, such as excessive deformation of portions of the enclosure, plastic deformation of portions of the enclosure, and/or buckling of portions of the enclosure.\",\n \"Accordingly, embodiments described herein may help to reduce costs of lifting enclosures.\",\n \"II.\",\n \"Example Apparatus A.\",\n \"Three Dimensional Structural Frame Members FIG.\",\n \"1 shows a three dimensional structural frame member 100, according to an example embodiment.\",\n \"The three dimensional structural frame member 100 includes a frame member 110, a mounting flange 120, and a transverse stiffener 130.Moreover, the frame member 110 includes a variable cross section three dimensional structure 112 that includes a first end 114, a second end 116, a first (bottom) flange 140 that may define a first interior wall, a web 142 that may define a second interior wall, and a second (top) flange 144 that may define a third interior wall.\",\n \"The first end 114 is wider than the second end 116.With this arrangement, the variable cross section three dimensional structure 112 may comprise an open three dimensional structure comprising the first flange 140, the web 142, and the second flange 144.The frame member 110 may comprise a variety of materials.\",\n \"For instance, in some embodiments, the frame member 110 may comprise steel.\",\n \"And in some such embodiments, the frame member 110 may comprise sheet metal of variable thickness and post processing treatments.\",\n \"Moreover, in some embodiments, the variable cross section three dimensional structure 112 may comprise a single piece of sheet metal.\",\n \"Further, in some embodiments, the variable cross section three dimensional structure 112 and mounting flange 120 may comprise a single piece of sheet metal.\",\n \"The variable cross section three dimensional structure 112 and mounting flange 120 may comprise the same or similar material as the frame member 110.As shown in FIG.\",\n \"1, the mounting flange 120 may be located at the second end 116 of the variable cross section three dimensional structure 120 and at least partially enclose the second end 116.The mounting flange 120 may include through holes 122 for mounting the frame member 110.In the illustrated example, the mounting flange 120 may further include second through holes 124, and the first end 114 may further include third through holes 118.Further, as shown in FIG.\",\n \"1, the transverse stiffener 130 may be positioned within the variable cross section three dimensional structure 112 and comprises a rigid support structure rigidly fixed to the first flange 140, the web 142, and the second flange 144 of the variable cross section three dimensional structure 112.In some embodiments, the transverse stiffener 130 may be welded to the first flange 140, the web 142, and the second flange 144 of the variable cross section three dimensional structure 112 as shown in FIG.\",\n \"1-1.And in some such embodiments, the transverse stiffener 130 may be fillet welded to each of the first flange 140, the web 142, and the second flange 144.The first flange 140, the web 142, and the second flange 144 may take various different forms in various different embodiments.\",\n \"For instance, in some embodiments, the first flange 140, the web 142, and the second flange 144 may have the same thickness.\",\n \"However, in other embodiments, at least two of the first flange 140, the web 142, and the second flange 144 may have different thicknesses.\",\n \"Moreover, in some embodiments, each of the first flange 140, the web 142, and the second flange 144 may have different thicknesses.\",\n \"The first flange 140, the web 142, and the second flange 144 may have other parameters that are the same or different as well.\",\n \"For instance, any XYZ dimension of the first flange 140 may be the same as or different than the corresponding XYZ dimension of the web 142 and/or the second flange 144, such as width, depth, and height.\",\n \"Further, the moment of inertia of the first flange 140 may be the same as or different than the moment of inertia of the web 142 and/or the second flange 144.Moreover, in some embodiments, the first flange 140, the web 142, and/or the second flange 144 may have varying thicknesses, varying XYZ dimensions, and/or varying moments of inertia.\",\n \"The transverse stiffener 130 may comprise a variety of materials in variable thicknesses.\",\n \"For instance, in some embodiments, the transverse stiffener 130 may comprise the same or similar material as the frame member 110.However, in other embodiments, the transverse stiffener 130 may comprise a different material than the frame member 110.Further still, as shown in FIG.\",\n \"1, the three dimensional structural frame member 100 may further include a second transverse stiffener 132 positioned within the variable cross section three dimensional structure 112 and comprise a rigid support structure rigidly fixed to the first flange 140, the web 142, and the second flange 144 of the variable cross section three dimensional structure 112.The second transverse stiffener 132 may comprise any of the materials that the transverse stiffener 130 comprises.\",\n \"In some embodiments, the second transverse stiffener 132 may comprise the same or similar material as the first transverse stiffener 130 and/or the frame member 110.However, in other embodiments, the second transverse stiffener 132 may comprise a different material than the transverse stiffener 130 and/or the frame member 110.The second transverse stiffener 132 may be welded to the first flange 140, the web 142, and the second flange 144 in the same or similar way as the transverse stiffener 130 is welded to the first flange 140, the web 142, and the second flange 144.The transverse stiffener 130 and/or the second transverse stiffener 132 may strengthen the three dimensional structural frame member 100, for example, by improving resistance of the three dimensional structural frame member 100 to deformation, bending, rupturing, breaking, and other modes of failure.\",\n \"The location of the transverse stiffener 130 in the variable cross section three dimensional structure 112 with respect to the first end 114 and the second end 116 may be selected based on predetermined loading of the three dimensional structural frame member 100 (e.g., bending moments and/or torsional loading).\",\n \"Similarly, the location of the second transverse stiffener 132 in the variable cross section three dimensional structure 112 with respect to the first end 114 and second end 116 and/or the transverse stiffener 130 may be selected based on predetermined loading of the three dimensional structural frame member 100.Other parameters of the three dimensional structural frame member 100 may be selected based on predetermined loading of the three dimensional structural frame member 100 as well, such as the material or thickness of the frame member 110, width of the first end 116, and width of the second end 118.FIG.\",\n \"2 shows aspects of a three dimensional structural frame member 200, according to an example embodiment.\",\n \"The three dimensional structural frame member 200 is similar to three dimensional structural frame member 100, except that the three dimensional structural frame member 200 includes a three dimensional structure 212 that does not have a variable cross section.\",\n \"Instead, the three dimensional structure 212 includes two ends that have substantially equal widths.\",\n \"For instance, a first end (not shown in FIG.\",\n \"2) has a first width, a second end 216 has a second width, and the first width and the second width are substantially equal.\",\n \"With this arrangement, the three dimensional structure 212 may have a constant cross section.\",\n \"The term “substantially equal,” as used in this disclosure, means exactly equal or one or more deviations from exactly equal that do not significantly impact lifting enclosures as described herein.\",\n \"As shown in FIG.\",\n \"2, the three dimensional structural frame member 200 includes a frame member 210 that has the second end 216, a mounting flange 220 at the second end 216 that at least partially encloses the second end 216, and a transverse stiffener 230 positioned within the three dimensional structure 212 comprising a rigid support structure rigidly fixed to a first (bottom) flange 240 that may define a first interior wall, a web 242 that may define a second interior wall, and a second (top) flange 244 that may define a third interior wall of the three dimensional structure 212.In addition, as shown in FIG.\",\n \"2, the three dimensional structural frame member 200 may further include a second transverse stiffener 232 positioned within the three dimensional structure 212 comprising a rigid support structure rigidly fixed to the first flange 240, the web 242, and the second flange 244.The three dimensional structural frame member 200 may also include through holes, second through holes, and third through holes similar to through holes 122, second through holes 124, and third through holes 118 in the three dimensional structural frame member 100.Components of the three dimensional structural frame member 200 of FIG.\",\n \"2 may have the same or similar arrangement and function in a similar manner as similarly numbered components of the three dimensional structural frame member 100 of FIG.\",\n \"1 unless otherwise noted.\",\n \"For instance, in some embodiments, the three dimensional structure 212 may comprise a single piece of sheet metal.\",\n \"Moreover, in some embodiments, the three dimensional structure 212 and mounting flange 220 may comprise a single piece of sheet metal.\",\n \"Further, in some embodiments, the three dimensional structure 212 may comprise an open three dimensional structure comprising the first flange 240, the web 242, and the second flange 244.Further still, in some embodiments, the transverse stiffener 230 may be welded to the first flange 240, the web 242, and the second flange 244 of the three dimensional structure 212.The transverse stiffener 230 may be welded to the first flange 240, the web 242, and the second flange 244 of the three dimensional structure 212 in the same or similar way as the transverse stiffener 130 is welded to the first flange 140, the web 142, and the second flange 144 of the three dimensional structure 112.In addition, the second transverse stiffener 232 may be welded to the first flange 240, the web 242, and the second flange 244 of the three dimensional structure 212 in the same or similar way as the transverse stiffener 230 is welded to the first flange 240, the web 242, and the second flange 244 of the three dimensional structure 212.B.\",\n \"Three Dimensional Structural Frames FIG.\",\n \"3a shows a three dimensional structural frame 300, according to an example embodiment.\",\n \"Three dimensional structural frame 300 includes a first three dimensional structural frame member 300A and a second three dimensional structural frame member 300B joined together at their first ends 314A, 314B by a plurality of fasteners 350 as shown in FIG.\",\n \"3a-1.In some embodiments, the plurality of fasteners 350 may comprise three fasteners.\",\n \"And in some such embodiments, the fasteners of the plurality of fasteners 350 may comprise screws.\",\n \"Moreover, in some embodiments, the plurality of fasteners 350 may be installed in through holes in first ends 314A, 314B similar to through holes 118 in three dimensional structural frame member 100.In the illustrated example, the first three dimensional structural frame member 300A and second three dimensional structural frame member 300B may take the form of or be similar in form to the three dimensional structural frame member 100.Accordingly, components of the first three dimensional structural frame member 300A of FIG.\",\n \"3a may have the same arrangement and function in a similar way as similarly numbered components of the three dimensional structural frame member 100 of FIG.\",\n \"1, and components of the second three dimensional structural frame member 300B of FIG.\",\n \"3a may have the same arrangement and function in a similar way as the similarly numbered components of the three dimensional structural frame member 100 of FIG.\",\n \"1.FIG.\",\n \"3b shows a back view of the three dimensional structural frame 300.Further, FIG.\",\n \"3c shows a top view of the three dimensional structural frame 300, and FIG.\",\n \"3d shows a front view of the three dimensional structural frame 300.As shown in FIGS.\",\n \"3b and 3c, the three dimensional structural frame 300 may further include a support beam 360 connected to the three dimensional structure 312A of the first three dimensional structural frame member 300A and the three dimensional structure 312B of the second three dimensional structural frame member 300B.\",\n \"The support beam 360 may comprise the same or similar material as the frame member 110.In some embodiments, a three dimensional structural frame may include a connector for a fall protection harness (which may be referred to as a fall prevention cleat).\",\n \"FIG.\",\n \"4 shows a three dimensional structural frame 400 that includes a connector 470 for a fall protection harness, according to an example embodiment.\",\n \"The three dimensional structural frame 400 includes a first three dimensional structural frame member 400A and a second three dimensional structural frame member 400B joined together at their first ends 414A and 414B by a plurality of fasteners 450 as shown in FIG.\",\n \"4-1.As shown in FIGS.\",\n \"4 and 4-1, the connector 470 is between the first end 414A of the first three dimensional structural frame member 400A and the first end 414B of the second three dimensional structural frame member 400B.\",\n \"With this arrangement, the plurality of fasteners 450 may join the connector 470 to the first three dimensional structural frame member 400A and the second three dimensional structural frame member 400B.\",\n \"Moreover, in some embodiments, the connector 470 may be welded to the three dimensional structure 412A of the first three dimensional structural frame member 400A and/or the three dimensional structure 412B of the second three dimensional structural frame member 400B.\",\n \"In some examples, the connector 470 may be fillet welded to the three dimensional structure 412A and/or the three dimensional structure 412B.\",\n \"The connector 470 may comprise a variety of materials.\",\n \"For instance, in some embodiments, the connector 470 may comprise steel.\",\n \"And in some such embodiments, the connector 470 may comprise ½ inch hot rolled steel (HRS).\",\n \"Further, in some embodiments, the connector 470 may strengthen the three dimensional structural frame 400 in the same or similar way as the transverse stiffener 130 and/or the second transverse stiffener 132 strengthen the three dimensional structural frame member 100.In the illustrated example, the first three dimensional structural frame member 400A may take the form of or be similar in form to the first three dimensional structural frame member 300A, and second three dimensional structural frame member 400B may take the form of or be similar in form to the second three dimensional structural frame member 300B.\",\n \"Accordingly, the first three dimensional structural frame member 400A may have the same arrangement and function in a similar way as the first three dimensional structural frame member 300A, and the second three dimensional structural frame member 400B may have the same arrangement and function in a similar way as the second three dimensional structural frame member 300B.\",\n \"Moreover, in some embodiments, three dimensional structural frames may have more than one connector for a fall protection harness.\",\n \"FIG.\",\n \"5 shows a three dimensional structural frame 500 that includes a connector 570 for a fall protection harness, a second connector 572 for the fall protection harness, and a third connector 574 for the fall protection harness.\",\n \"The three dimensional structural frame 500 includes a first three dimensional structural frame member 500A and a second three dimensional structural frame member 500B joined together at their first ends 514A and 514B by a plurality of fasteners 550.The connector 570 may be between the first end 514A of the first three dimensional structural frame member 500A and the first end 515B of the second three dimensional structural frame member 500B.\",\n \"In addition, the connector 570 may be joined in the three dimensional structural frame 500 in the same or similar way as the connector 470 may be joined in the three dimensional structural frame 400.In addition, the second connector 572 may be located between the first end 514A and the second end 516A of the first three dimensional structural frame member 500A.\",\n \"In some embodiments, the second connector 572 may be welded to the three dimensional structure 512A of the first three dimensional structural frame member 500A in the same or similar way as the connector 470 is welded to the three dimensional structure 412A and/or the three dimensional structure 412B.\",\n \"Moreover, the third connector 574 may be located between the first end 514B and the second end 516B of the second three dimensional structural frame member 500B.\",\n \"In some embodiments, the third connector 574 may be welded to the three dimensional structure 512B of the second three dimensional structural frame member 500B in the same or similar way as the connector 470 is welded to the three dimensional structure 412A and/or the three dimensional structure 412B.\",\n \"Further, in some embodiments, the connector 570, the second connector 572, and the third connector 574 may strengthen the three dimensional structural frame 500 in the same or similar way as the transverse stiffener 130 and/or the second transverse stiffener 132 strengthen the three dimensional structural frame member 100.In the illustrated example, the first three dimensional structural frame member 500A may take the form of or be similar in form to the first three dimensional structural frame member 300A, and second three dimensional structural frame member 500B may take the form of or be similar in form to the second three dimensional structural frame member 300B.\",\n \"Accordingly, the first three dimensional structural frame member 500A may have the same arrangement and function in a similar way as the first three dimensional structural frame member 300A, and the second three dimensional structural frame member 500B may have the same arrangement and function in a similar way as the second three dimensional structural frame member 300B.\",\n \"In some embodiments, a three dimensional structural frame may be comprised of a single member.\",\n \"FIG.\",\n \"6 shows a three dimensional structural frame 600, according to an example embodiment.\",\n \"The three dimensional structural frame includes a frame member 610, mounting flanges 620 and 630, a center support 640, and transverse stiffeners 650 and 652.The frame member 610 includes an elongated three dimensional structure 612 that has a first side 614, a first end 615, a second side 616, a second end 617, and a center support portion 618.The first side 614 has a variable cross section from the first end 615 to the center support portion 618, and the second side 616 has a variable cross section from the second end 617 to the center support portion 618.The elongated three dimensional structure 612 further includes a first (bottom) flange 660 that may define a first interior wall, a web 662 that may define a second interior wall, and second (top) flange 664 that may define a third interior wall.\",\n \"With this arrangement, the elongated three dimensional structure 612 may comprise an open three dimensional structure with the first flange 660, the web 662, and the second flange 664 and may have a varying cross section.\",\n \"The frame member 610 may comprise the same or similar material as the frame member 110.As shown in FIG.\",\n \"6, the mounting flange 620 may be located at the first end 615 and at least partially enclose the first end 615, and the mounting flange 630 may be located at the second end 616 and at least partially enclose the second end 616.The mounting flange 620 may include through holes 622 for mounting the frame member 610.In the illustrated example, the mounting flange 620 may further include second through holes 624.The mounting flange 630 in turn may include through holes 632 for mounting the frame member 610.In the illustrated example, the mounting flange 630 may further include second through holes 634.The frame member 610 may comprise the same or similar material as the frame member 110.Moreover, in some embodiments, the elongated three dimensional structure 612 may comprise a single piece of sheet metal.\",\n \"Further, in some embodiments, the elongated three dimensional structure 612 and mounting flanges 620, 630 may comprise a single piece of sheet metal.\",\n \"The elongated three dimensional structure 612 and mounting flanges 620 and 630 may comprise the same or similar material as the frame member 610.Further, as shown in FIG.\",\n \"6, the center support 640 is mounted at the center support portion 618.The center support 640 may comprise the same or similar material as the frame member 610.Further still, as shown in FIG.\",\n \"6, the transverse stiffener 650 is positioned within the elongated three dimensional structure 612 on the first side 614 of the elongated three dimensional structure 612 and comprises a rigid support structure rigidly fixed to the first flange 660, the web 662, and the second flange 664, and the transverse stiffener 652 is positioned within the elongated three dimensional structure 612 on the second side 616 of the elongated three dimensional structure 612 and comprises a rigid support structure rigidly fixed to the first flange 660, the web 662, and the second flange 664.In some embodiments, the transverse stiffeners 650, 652 may be welded to the first flange 660, the web 662, and the second flange 664 in the same or similar way as the transverse stiffener 130 is welded to the first flange 340, the web 342, and the second flange 344.The transverse stiffeners 650, 652 may comprise a variety of materials in variable thicknesses.\",\n \"For instance, in some embodiments, the transverse stiffeners 650, 652 may comprise the same or similar material as the frame member 610.However, in other embodiments, the transverse stiffeners 650, 652 may comprise a different material than the elongated three dimensional structure 612.Further still, as shown in FIG.\",\n \"6, the three dimensional structural frame 600 may further include a second transverse stiffener 654 within the elongated three dimensional structure 612 on the first side 614 of the elongated three dimensional structure 612 and comprises a rigid support structure rigidly fixed to the first flange 660, the web 662, and the second flange 664, and a second transverse stiffener 656 within the elongated three dimensional structure 612 on the second side 616 of the elongated three dimensional structure 612 and comprises a rigid support structure rigidly fixed to the first flange 660, the web 662, and the second flange 664.The second transverse stiffeners 654, 656 may comprise any of the materials that the transverse stiffeners 650, 652 comprise.\",\n \"In some embodiments, the second transverse stiffeners 654, 656 may comprise the same or similar material as the transverse stiffeners 650, 652 and/or the frame member 610.However, in other embodiments, the second transverse stiffeners 654, 656 may comprise a different material than the transverse stiffeners 650, 652 and/or the frame member 610.The second transverse stiffeners 650, 652 may be welded to the first flange 660, the web 662, and the second flange 664 in the same or similar way as the transverse stiffeners 650, 652 are welded to the first flange 660, the web 662, and the second flange 664.The transverse stiffeners 650, 652 and/or the second transverse stiffener 654, 656 may strengthen the three dimensional structural frame 600, for example, by improving resistance of the three dimensional structural frame 600 to deformation, bending, rupturing, breaking and other modes of failure.\",\n \"Similarly, the center support 640 may strengthen the three dimensional structural frame 600, for example, by improving resistance of the three dimensional structural frame 600 to deformation, bending, rupturing, breaking and other modes of failure.\",\n \"The location of the transverse stiffeners 650, 652 in the elongated three dimensional structure 612 with respect to the first end 615 and the second end 617 may be selected based on predetermined loading of the three dimensional structural frame 600.Similarly, the location of the second transverse stiffeners 654, 656 in the elongated three dimensional structure 612 with respect to the first end 615 and second end 617 and/or the transverse stiffeners 650, 652 may be selected based on predetermined loading of the structural frame 600.Other parameters of the three dimensional structural frame member 600 may be selected on predetermined loading of the three dimensional structural frame member 600 as well, such as the material or thickness of the frame member 610, width of the first end 615, and width of the second end 617.In some embodiments, a three dimensional structural frame that includes a single three dimensional structure may include a connector for a fall protection harness.\",\n \"FIG.\",\n \"7 shows a three dimensional structural frame 700 that includes a connector 770 for a fall protection harness, according to an example embodiment.\",\n \"The three dimensional structural frame 700 includes a frame member 710, mounting flanges 720 and 730, a center support 740, transverse stiffeners 750 and 752, and second transverse stiffeners 754 and 756.Components in the three dimensional structural frame 700 of FIG.\",\n \"7 may have the same or similar arrangement and function in a similar manner as similarly numbered components of the three dimensional structural frame 600 of FIG.\",\n \"6 unless otherwise noted.\",\n \"As shown in FIG.\",\n \"7, the center support includes the connector 770.The connector 770 may take the form of or be similar in form to the connector 470.In some embodiments, the connector 770 may strengthen the three dimensional structural frame 700 in the same or similar way that the transverse stiffeners 650, 652 and/or the second transverse stiffeners 654, 656 strengthen the three dimensional structural frame 600.In some embodiments, a three dimensional structural frame that includes a single three dimensional structure may have two or more connectors for a fall protection harness.\",\n \"For instance, in some embodiments, a three dimensional structural frame that includes a single three dimensional structure may have three connectors arranged in the same or similar was as connectors 570, 572, and 574 are arranged in the three dimensional structural frame 500.In addition, in some embodiments, three dimensional structural frames may include a three dimensional structure that has a constant cross section similar to the three dimensional structure 212.For instance, in some embodiments, a structural frame may comprise two three dimensional structural frame members that are joined at their first ends, where each three dimensional structural frame member takes the form of or is similar in form to the three dimensional structural frame member 200.And in some such embodiments, the three dimensional structural frame may include one or more connectors similar to connector 470.Moreover, in some embodiments, a three dimensional structural frame may comprise a single three dimensional structure with a constant cross section similar to the cross section of three dimensional structure 212.And in some such embodiments, the three dimensional structural frame may include one or more connectors similar to connector 470.Further, in some embodiments, a three dimensional structural frame may comprise a first three dimensional structural frame member that takes the form of or is similar in form to the three dimensional structural frame member 100 and a second three dimensional structural frame member that takes the form of or is similar in form to the three dimensional structural frame member 200, where the first and second three dimensional structural frame members are joined at their first ends.\",\n \"And in some such embodiments, the three dimensional structural frame may include one or more connectors similar to connector 470.C.\",\n \"Enclosures FIG.\",\n \"8 shows an enclosure 800, according to an example embodiment.\",\n \"The enclosure includes a plurality of three dimensional structural frames 810, opposing wall portions 820 interconnected by the plurality of three dimensional structural frames 810, and a roof 840 secured to the plurality of the three dimensional structural frames 810.In some embodiments, the enclosure 800 may have length of forty five feet.\",\n \"The plurality of three dimensional structural frames 810 may take various different forms in various different embodiments.\",\n \"For purposes of illustration, the plurality of three dimensional structural frames 810 includes four three dimensional structural frames 812, 814, 816, 818.However, in other examples, the plurality of three dimensional structural frames 810 may include more or less than four three dimensional structural frames.\",\n \"The number of three dimensional structural frames in the plurality of three dimensional structural frames 810 may be selected based in part on a predetermined length and/or loading of the enclosure 800.The three dimensional structural frames 812, 814, 816, and 818 may comprise any of the three dimensional structural frames described herein, including the three dimensional structural frames 300, 400, 500, 600, and 700 and example three dimensional structural frames that include a three dimensional structure that has a constant cross section.\",\n \"In some embodiments, the three dimensional structural frames 812, 814, 816, and 818 may be the same as each other.\",\n \"However, in other embodiments, two or more of the three dimensional structural frames 812, 814, 816, and 818 may be different.\",\n \"With this arrangement, the plurality of three dimensional structural frames 810 may comprise a combination of any of the three dimensional structural frames described herein.\",\n \"The opposing wall portions 820 include a plurality of uniform wall sections 830.For purposes of illustration, the plurality of wall sections 830 includes four wall sections 832, 834, 836, and 838.However, in other examples, plurality of wall sections 830 may include more or less than four wall sections.\",\n \"FIG.\",\n \"9 shows aspects of a wall section 900, according to an example embodiment.\",\n \"The wall sections 832, 834, 836, and 838 may take the form of or be similar in form to the wall section 900.The wall section 900 includes a wall panel portion 910, a top wall portion 920, sidewall portions 930A, 930B, and a bottom wall portion 940.In some embodiments, the wall section 900 may comprise a single piece of formed sheet metal.\",\n \"Moreover, in some embodiments, the wall section 900 may comprise steel.\",\n \"Further, in some embodiments, the wall section 900 may be the same or similar material as the frame member 110.The sidewall portions 930A, 930B may be joined to sidewall portions of other wall sections to form opposing wall portions, such as the opposing wall portions 820.The bottom wall portion 940 is further shown in FIG.\",\n \"9-1.For instance, the bottom wall portion 940 may include a support flange 942 that wraps around the bottom wall portion 940.With this arrangement, the support flange 942 may strengthen the bottom wall portion 940, for example, by improving resistance of the bottom wall portion 940 to deformation, bending, rupturing, breaking, and other modes of failure.\",\n \"The support flange 942 includes a through hole 944.Further, as shown in FIG.\",\n \"9-1, the bottom wall portion 940 includes a through hole 946.When wall section 900 is part of opposing walls of an enclosure, such as opposing walls 820 of enclosure 800, a fastener may be installed in through hole 946 to secure wall section 900 to ground or a mounting surface that the enclosure is located over, such as a skid or frame on which equipment is disposed.\",\n \"FIG.\",\n \"10a shows three dimensional structural frames 1010 attached to walls sections 1030, according to an example embodiment.\",\n \"In particular, FIG.\",\n \"10a shows five three dimensional structural frames 1010A-E connected to four wall sections 1030A-D.\",\n \"The three dimensional structural frames 1010A-E have through holes 1012A-E, respectively and the wall sections 1030A-D have through holes 1032A-D, respectively.\",\n \"The three dimensional structural frames 1010A-E may take the form of any of or be similar in form to any of the three dimensional structural frames described herein, and the wall sections 1030A-D may take the form of or be similar in form to the wall section 900.As shown in FIG.\",\n \"10a, a three dimensional structural frame is attached to a top wall portion, such as top wall portion 940, of a wall section.\",\n \"Moreover, as shown in FIG.\",\n \"10a, in some embodiments, the ends of certain three dimensional structural frames overlap and are simultaneously attached to two wall sections.\",\n \"For instance, the end of three dimensional structural frame 1010B overlaps and is simultaneously attached to wall section 1030A and wall section 1030B, the end of three dimensional structural frame 1010C overlaps and is simultaneously attached to wall section 1030B and 1030C, and the end of three dimensional structural frame 1010D overlaps and is simultaneously attached to wall section 1030C and wall section 1030D.\",\n \"Three dimensional structural frames 1010 may be attached to wall sections by hardware (e.g., fasteners) installed in through holes, such as through holes 122, 322A and 322B, and 622 and 632.Moreover, wall sections 1010 may be connected by sidewall portions, such as sidewall portions 930A and 930B.\",\n \"In some embodiments, sidewall portions may be connected by a plurality of rivets (not shown).\",\n \"And in some such embodiments, the plurality of rivets may comprise one rivet per six inch length of the sidewall portion.\",\n \"Further, in some embodiments, a gasket may be located between wall sections, such as a gasket 1040 is located between wall section 1030A and wall section 1030B.\",\n \"As shown in FIG.\",\n \"10a, the gasket 1040 may be located between the sidewall portion of wall section 1030A and the sidewall portion of wall section 1030B.\",\n \"In some embodiments, gasket 1040 may comprise a silicone bead, polyurethane, or structural adhesive (e.g., weatherproof adhesive).\",\n \"In addition, in some embodiments, gasket 1040 may weatherproof the plurality of rivets used to join the wall sections.\",\n \"Further still, in some embodiments, the enclosure may further include a plurality of support members that extend between the opposing wall portions (not shown in FIG.\",\n \"8).\",\n \"In some embodiments, the plurality of support members may have the same or similar material as the frame member 110.The plurality of support members may strengthen the enclosure, for example, by improving resistance of the enclosure 800 to plastic deformation and/or buckling.\",\n \"Moreover, in some embodiments, a roof of an enclosure, such as the roof 840, may include a plate (or a plurality of plates) secured to the three dimensional structural frames.\",\n \"And in some such embodiments, the plate may comprise sheet metal and/or perforated sheet metal.\",\n \"Further, in some embodiments, the roof can further include a weatherproof membrane (or a plurality of membranes) overlaying the plate and attached to wall panel portions of wall sections.\",\n \"FIG.\",\n \"10b shows wall sections 1080 connected to a support member 1090, according to an example embodiment.\",\n \"The enclosure 800 may further include one or more support members that may take the form of or be similar in form to the support member 1090.The support member 1090 may tie each of the wall sections 1080 together.\",\n \"In addition, the support member 1080 may act as a lateral brace, improve rigidity of the wall sections 1080, and/or improve resistance of the wall sections 1080 to shear loading, torsional loading, and axial loading.\",\n \"As shown in FIG.\",\n \"10b, the wall sections 1080 include twelve wall sections 1080A-L.\",\n \"However, in other examples, the wall sections 1080 may include more or less than twelve wall sections.\",\n \"The number of wall sections in the wall sections 1080 may be selected based in part on a predetermined length and/or loading of an enclosure.\",\n \"In the illustrated example, certain wall sections of the wall sections 1080 may have different lengths (e.g., wall sections 1080A and 1080D) and/or different widths (e.g., wall sections 1080A, 1080D, and 1080H).\",\n \"The support member 1090 may take various different forms in various different embodiments.\",\n \"In some embodiments, the support member 1090 may comprise steel.\",\n \"Moreover, in some embodiments, the support member 1090 may be connected to an end of each wall section of the wall sections 1080, such as a top end of the wall section when the wall section is oriented substantially perpendicular to ground.\",\n \"The term “substantially perpendicular,” as used in this disclosure, refers to exactly perpendicular or one or more deviations from exactly perpendicular that do not significantly impact lifting an enclosure as described herein.\",\n \"FIG.\",\n \"10c shows a side view of the wall sections 1080 connected to the support member 1090, and FIG.\",\n \"10c-1 shows aspects of the wall sections 1080 connected to the support member 1090.As shown in FIG.\",\n \"10c-1, in some embodiments, the support member 1090 may have a C-shaped cross section.\",\n \"And in some such embodiments, the support member 1090 may be oriented, such that an open portion 1092 of its cross section may face away from the wall sections 1080.Other cross sectional shapes of the support member 1090 are possible as well, including rectangular or triangular.\",\n \"The length of the support member 1090 may be selected based at least in part on the number of wall sections in the wall sections 1080.In addition, the thickness of the support member 1090 may be selected based at least in part on a predetermined loading of the wall sections 1080 and/or an enclosure (e.g., the thickness of the support member 1090 may increase as the predetermined loading increases).\",\n \"In addition, the support member 1090 may define a wire way for electrical cabling associated with an enclosure.\",\n \"In some embodiments, the wire way may be partitioned to separate electrical cabling for AC circuits associated with the enclosure and electrical cabling for DC circuits associated with the enclosure.\",\n \"Moreover, in some embodiments, after electrical cabling is installed in the support member 1090, a closing plate (not shown) may be connected over the open portion 1092 of the support member 1090.With this arrangement, the closing plate may help to seal and protect the electrical cabling.\",\n \"An enclosure may include at least two support members that take the form of the support member 1090.A first support member may be connected to a first group of wall sections and a second support member may be connected to a second group of wall sections.\",\n \"The first group of wall sections may be substantially parallel to the second group of wall sections.\",\n \"With this arrangement, the first support member may be substantially parallel to the second support member.\",\n \"FIG.\",\n \"11a shows aspects of a roof 1100 of an enclosure, according to an example embodiment.\",\n \"The roof 840 may take the form of or be similar in form to the roof 1100.As shown in FIG.\",\n \"11a, the roof 1100 includes plates attached to three dimensional structural frames.\",\n \"In particular, plate 1110A and plate 1110B are secured to three dimensional structural frames 1120 and 1122.Plates 1110A and plates 1110B may be secured to three dimensional structural frames 1120 and 1122 by hardware.\",\n \"In some embodiments, the hardware may take the form of a plurality of fasteners, such as a plurality of rivets.\",\n \"The three dimensional structural frames 1120 and 1122 may take the form of or be similar in form to three dimensional structural frame 300 and/or three dimensional structural frame 600.With this arrangement, the variable cross section three dimensional structure of the three dimensional structural frames 1120 and 1122 may create a slope to the roof 1110 and help to shed water, other fluids, and debris from the roof 1100.In other examples, the three dimensional structural frames 1120 and 1122 may take the form of or be similar in form to three dimensional structural frames having a three dimensional structure with a constant cross section.\",\n \"With this arrangement, the three dimensional structure of the three dimensional structural frames 1120 and 1122 may help to provide structural support for the roof 1100.In addition, in some embodiments, other components may be attached to three dimensional structural frames 1120 and 1122, including ceiling panels and insulation.\",\n \"Further, as shown in FIG.\",\n \"11a, the roof 1100 includes weatherproof membranes 1130A and 1130B overlaying plates secured to three dimensional structural frames (not shown).\",\n \"The membranes 1130A and 1130B may be attached to wall panel portions of the wall sections, such as wall portion 910 of the wall section 900.For instance, the membranes 1130A and 1130B may be attached to wall panel portions of the walls sections by hardware, such as a plurality of fasteners.\",\n \"In some such embodiments, the plurality of fasteners may be installed in through holes of the wall sections, such as through holes 1032A-1032D, and/or through holes of three dimensional structural frames, such as through holes 1012A-E. And in some such embodiments, the plurality of fasteners may comprise a plurality of rivets.\",\n \"The weatherproof membranes 1130A and 1130B may help to reduce moisture from passing through the roof 1100.In addition, the weatherproof membranes 1130A and 1130B may help to insulate the roof 1100.Further still, as shown in FIG.\",\n \"11a, the weatherproof membranes 1130A and 1130B may cover plates and three dimensional structural frames, except for connectors for fall protection harness 1170A, 1170B, and 1170C of the three dimensional structural frames.\",\n \"The connectors 1170A, 1170B, and 1170C may take the form of or be similar in form to the connector 470 and/or the connector 770.The connectors 1170A, 1170B, and 1170C may improve safety of the roof 1100 and/or corresponding enclosure.\",\n \"For instance, when maintenance is performed on the roof 1100 and/or corresponding enclosure, fall protection harness may be installed in the connectors 1170A, 1170B, and 1170C to provide fall protection.\",\n \"FIG.\",\n \"11b shows three dimensional structural frames 1180 connected to a strengthening member 1190, according to an example embodiment.\",\n \"The enclosure 800 may further include a strengthening member that may take the form of or be similar in form to the strengthening member 1190.The strengthening member 1190 may tie each three dimensional structural frame of the three dimensional structural frames 1180 together.\",\n \"In addition, the strengthening member 1190 may improve resistance of the three dimensional structural frames 1180 to torsion.\",\n \"As shown in FIG.\",\n \"11b, the three dimensional structural frames 1180 include twenty-two three dimensional structural frames 1180A-V.\",\n \"However, in other examples, the three dimensional structural frames 1180 may include more or less than twenty-two three dimensional structural frames.\",\n \"The number of three dimensional structural frames in the three dimensional structural frames 1180 may be selected based at least in part on a predetermined length and/or loading of an enclosure in the same or similar way as the number of three dimensional structural frames in the plurality of three dimensional structural frames 810 is selected.\",\n \"Moreover, the three dimensional structural frames 1180A-V may take the form of any of the three dimensional structural frames described herein in the same or similar way as the structural frames 812, 814, 816, 818 of the plurality of structural frames 810.The strengthening member 1190 may take various different forms in various different embodiments.\",\n \"In some embodiments, the strengthening member 1190 may comprise steel.\",\n \"Moreover, in some embodiments, the strengthening member 1190 may be connected to a center of each three dimensional structural frame of the three dimensional structural frames 1180.FIG.\",\n \"11b-1 shows aspects the three dimensional structural frames 1180 connected to the strengthening member 1190.As shown in FIG.\",\n \"11b-1, in some embodiments, the strengthening member 1190 may have a U-shaped cross section.\",\n \"And in some such embodiments, the strengthening member 1190 may be oriented, such that an open portion (not shown) of its cross section faces toward ground.\",\n \"Other cross sectional shapes of the strengthening member are possible as well, including rectangular and triangular.\",\n \"The thickness of the strengthening member 1190 may be selected based at least in part on a predetermined loading of the three dimensional structural frames 1180 and/or an enclosure (e.g., the thickness of the strengthening member 1190 may increase as the predetermined loading increases).\",\n \"As shown in FIG.\",\n \"11b, each three dimensional structural frame member of the three dimensional structural frame members 1180 connected to the strengthening member 1190 may be spaced apart from adjacent three dimensional structural frame members a certain distance (e.g., 1180A is spaced apart from 1180B a distance 1196).\",\n \"In some embodiments, the distance between three dimensional structural frame members of the three dimensional structural frame members 1180 connected to the strengthening member 1190 may be substantially equal.\",\n \"However, in some embodiments, the distance between a first set of adjacent three dimensional structural frame members of the three dimensional structural frame members 1180 connected to the strengthening member 1190 (e.g., 1180A and 1180B) may be different than a second set of adjacent three dimensional structural frame members of the three dimensional structural frame members 1180 connected to the strengthening member 1190 (e.g., 1180M and 1180N).\",\n \"The distance between adjacent three dimensional structural frame members of the plurality of structural frame members 1180 connected to the strengthening member 1190 may have various different values.\",\n \"For instance, in some embodiments, the distance between adjacent three dimensional structural frame members of the structural frame members 1180 connected to the strengthening member 1190 may be between 4 inches and 2 feet, such as 4 inches, 6 inches, one foot, and two feet.\",\n \"The distance between adjacent three dimensional structural frame members of the structural frame members 1180 connected to the strengthening member 1190 may be based at least in part on a width of the three dimensional structural frame members 1180.In some such embodiments, the width of at least one three dimensional structural frame member of the three dimensional structural frame members 1180 may be 3 inches.\",\n \"Moreover, in some such embodiments, when a three dimensional structural frame member comprises a support beam (e.g., support beam 360), the width of the three dimensional structural frame member may be 4 inches.\",\n \"Further, as shown in FIG.\",\n \"11b, beams 1192 and 1194 may be connected between three dimensional structural frame 11801 and three dimensional structural frame 1180J.\",\n \"With this arrangement, beams 1192 and 1194 may define a penetration in a roof of an enclosure.\",\n \"In some embodiments, an exhaust component may be installed in the penetration.\",\n \"The beams 1192 and 1194 may take various different forms in various different embodiments.\",\n \"For instance, in some embodiments, the beams 1192 and 1194 may comprise steel.\",\n \"In addition, in some embodiments, the beams 1192 and 1194 may comprise C-channels.\",\n \"Moreover, in some embodiments, the beams 1192 and 1194 may be flush with a web of the three dimensional structural frames 11801 and 1180J (e.g., web 342A).\",\n \"Further, in some embodiments, the beams 1192 and 1194 may each be welded to the web of the three dimensional structural frames 11801 and 1180J.\",\n \"The thickness of the beams 1192 and 1194 may be selected based at least in part on a predetermined loading of the three dimensional structural frames 1180 and/or an enclosure (e.g., the thickness of the beams 1192 and 1194 may increase as the predetermined loading increases).\",\n \"FIG.\",\n \"12a shows an enclosure 1200, according to an example embodiment.\",\n \"The enclosure 1200 may include a plurality of three dimensional structural frames 1210, opposing wall portions 1220 interconnected by the plurality of three dimensional structural frames 1210, and a roof 1240 secured to at least some of the three dimensional structural frames of the plurality of three dimensional structural frames 1210.The opposing wall portions 1220 may include a plurality of wall sections 1230.In some embodiments, the roof 1240 may be secured to all of the three dimensional structural frames of the plurality of three dimensional structural frames 1210.With this arrangement, the roof 1240 may cover all of the three dimensional structural frames of the plurality of three dimensional structural frames 1210.Components of the enclosure 1200 of FIG.\",\n \"12a may have the same arrangement and function in a similar manner as similarly numbered components of the enclosure 800 of FIG.\",\n \"8.The enclosure 1200 may be used to surround equipment described herein.\",\n \"In some embodiments, the enclosure 1200 may have a length of forty five feet.\",\n \"Moreover, in some embodiments, the enclosure 1200 may be designed to withstand loads caused by wind that has a speed of 150 miles per hour.\",\n \"Further, in some embodiments, the enclosure 1200 may be secured to a mounting surface 1290 shown in FIG.\",\n \"12b.\",\n \"Equipment may be located over the mounting surface 1290.And in some such embodiments, the plurality of wall sections 1230 may be secured to the mounting surface 1290 via through holes in bottom wall portions of the wall sections, such as through holes 946.Further, in some embodiments, the enclosure 1200 may be secured to a mounting plane.\",\n \"D. Lift Plates FIG.\",\n \"13 shows a lift plate 1300, according to an example embodiment.\",\n \"The lift plate 1300 may engage the ends of a plurality of three dimensional structural frames, such as the plurality of three dimensional structural frames 810.The lift plate 1300 may include a planar portion 1310 comprising a series of a pattern of mounting holes 1312 for receiving hardware for securing the lift plate 1300 to the ends of the plurality of three dimensional structural frames and a connecting portion 1320 for engaging a harness that provides upward force to lift the plate and frames.\",\n \"The series of a pattern of mounting holes 1312 may include a first series of a pattern of mounting holes 1314 and a second series of a pattern of mounting holes 1316.The connecting portion 1320 may include a hole 1322 for receiving the harness.\",\n \"As shown in FIG.\",\n \"13, the hole 1322 may be located through the connecting portion 1320.In some embodiments, the lift plate 1300 may be configured to be secured to two or more three dimensional structural frames, such as twelve three dimensional structural frames.\",\n \"For instance, hardware may engage the first series of a pattern of mounting holes 1314 and through holes of the three dimensional structural frames, such as through holes 1012B and 1012C.\",\n \"Moreover, in some embodiments, the lift plate 1300 may be configured to be secured to two or more wall sections, such as four wall sections.\",\n \"For instance, hardware may engage the second series of a pattern of mounting holes 1316 and through holes of the wall sections, such as through holes 1032A-D.\",\n \"In some embodiments, the hardware may include fasteners, such as bolts and rivet nuts.\",\n \"The lift plate 1300 may comprise a variety of materials.\",\n \"For instance, in some embodiments, the lift plate 1300 may comprise steel.\",\n \"And in some such embodiments, the lift plate 1300 may comprise 5/16 inch hot rolled steel.\",\n \"Moreover, in other embodiments, the lift plate 1300 may comprise steel having other thicknesses.\",\n \"In some embodiments, a connecting portion of a lift plate may include a reinforcement plate.\",\n \"FIG.\",\n \"14a shows a lift plate 1400, according to an example embodiment.\",\n \"The lift plate 1400 includes a connecting portion 1420 that includes a reinforcement plate 1424.The lift plate 1400 may engage the ends of a plurality of three dimensional structural frames, such as the plurality of three dimensional structural frames 810.The lift plate 1400 may include a planar portion 1410 comprising a series of a pattern of mounting holes 1412 for receiving hardware for securing the lift plate 1400 to the ends of the plurality of three dimensional structural frames and the connecting portion 1420 for engaging a harness that provides upward force to lift the plate and frames.\",\n \"The series of a pattern of mounting holes 1412 may include a first series of a pattern of mounting holes 1414 and a second series of a pattern of mounting holes 1416.The connecting portion 1420 may include a hole 1422 for receiving the harness and the reinforcement plate 1424.As shown in FIG.\",\n \"14a, the hole 1422 may be located through the connecting portion 1420 and the reinforcement plate 1424.FIG.\",\n \"14b shows a perspective view of the lift plate 1400, according to an example embodiment.\",\n \"In some embodiments, the hardware may include fasteners, such as bolts and rivet nuts.\",\n \"Components of lift plate 1400 of FIG.\",\n \"14a may have the same arrangement and function in a similar manner as similarly numbered components of the lift plate 1300 of FIG.\",\n \"13.In addition, the lift plate 1400 may be secured to the ends of the plurality of three dimensional structural frames and wall sections in the same or similar way as the lift plate 1300 is secured to the ends of the plurality of three dimensional structural frames and wall sections.\",\n \"In some embodiments, the reinforcement plate 1424 may be welded to the connecting portion 1420.And in some such embodiments, the reinforcement plate 1424 may be fillet welded to the connecting portion 1420.Moreover, the reinforcement plate 1424 may comprise a variety of materials.\",\n \"For instance, in some embodiments, the reinforcement plate 1424 may comprise steel.\",\n \"And in some such embodiments, the reinforcement plate 1424 may comprise the same or similar material as the planar portion 1410 and the connecting portion 1420.The reinforcement plate 1424 may strengthen the lift plate 1400, for example, by improving resistance of the lift plate 1400 to deformation, bending, rupturing, breaking, and other modes of failure.\",\n \"Further, in some embodiments, the lift plate 1400 may have a second reinforcement plate 1426.FIG.\",\n \"14c shows a side view of the lift plate 1400, according to an example embodiment.\",\n \"As shown in FIG.\",\n \"14c, the second reinforcement plate 1426 may be located opposite the reinforcement plate 1424.The second reinforcement plate 1426 may have the same arrangement and function in a similar manner as the reinforcement plate 1424.Moreover, the second reinforcement plate 1426 may be welded to the connecting portion 1420 in the same or similar way as the reinforcement plate 1424 is welded to the connecting portion 1420.The second reinforcement plate 1426 may strengthen the lift plate 1400 in the same or similar way as the reinforcement plate 1400 strengthens the lift plate 1400.E.\",\n \"Liftable Enclosures FIG.\",\n \"15a shows a liftable enclosure 1500, according to an example embodiment.\",\n \"The liftable enclosure 1500 includes a plurality of the three dimensional structural frames 1510 and at least two lift plates 1520.The at least two lift plates 1520 may be used to lift the liftable enclosure 1500 with an upward force in a direction that is substantially parallel to a direction 1580.The term “substantially parallel,” as used in this disclosure, means exactly parallel or one or more deviations from exactly parallel that do not significantly impact lifting an enclosure as described herein.\",\n \"In the illustrated example, a first three dimensional structural frame 1512A may be located at a first end of the liftable enclosure 1500 and a second three dimensional structural frame 1512B may be located at a second end of the liftable enclosure 1500.Numerous three dimensional structural frames may be located between the first three dimensional structural frame 1512A and the second three dimensional structural frame 1512B.\",\n \"The three dimensional structural frames of the plurality of three dimensional structural frames 1510 may take the form of any of the three dimensional structural frames described herein.\",\n \"Moreover, in the illustrated example, the at least two lift plates 1520 may include six lift plates 1522A-F.\",\n \"However, in other examples, the at least two lift plates 1520 may include more or less six lift plates, such as two lift plates or eight lift plates.\",\n \"In some embodiments, when the at least two lift plates 1520 include six lift plates, the liftable enclosure 1500 may have a length of forty five feet.\",\n \"Moreover, in some embodiments, when the liftable enclosure 1500 has a length greater than forty five feet, the at least two lift plates 1520 may include more than six lift plates, such as eight lift plates.\",\n \"Lift plates may be equally distributed on two sides of the liftable enclosure 1500.For example, as shown in FIG.\",\n \"15a, when the at least two lift plates 1520 include six lift plates, three lift plates (1522A, 1522C, and 1522E) may be located on a first side of the liftable enclosure 1500, and three lift plates (1522B, 1522D, and 1522F) may be located on a second side of the liftable enclosure 1500.As shown in FIG.\",\n \"15a-1, the lift plate 1522A includes a planar portion 1523A comprising a series of a pattern of mounting holes 1525A for receiving hardware for securing the plate to the ends of the plurality of three dimensional structural frames 1510 and a connecting portion 1524A for engaging a harness that provides an upward force to lift the lift plate 1522A and the three dimensional structural frames 1510.The series of a pattern of mounting holes 1525A may include a first series of a pattern of mounting holes 1526A and a second series of a pattern of mounting holes 1527A.\",\n \"The connecting portion may further include a hole 1529A for receiving the harness and a reinforcement plate 1528B.\",\n \"The hole 1529A may be through the connecting portion 1524 and the reinforcement plate 1528B.\",\n \"The lift plates 1522B-F may take the form of or be similar in form to and function in a similar manner as the lift plate 1522A.\",\n \"The planar portion 1523A may take the form of or be similar in form to the planar portion 1410, the connecting portion 1524A may take the form of or be similar in form to the connecting portion 1420, the series of a pattern of mounting holes 1525A may take the form of or be similar in form to the series of a pattern of mounting holes 1412, the first series of a pattern of mounting holes 1526A may take the form of or be similar in form to the first series of a pattern of mounting holes 1414, the second series of a pattern of mounting holes 1527A may take the form of or be similar in form to the second series of a pattern of mounting holes 1416, the reinforcement plate 1528A may take the form of or be similar in form the reinforcement plate 1424, and the hole 1529A may take the form of or be similar in form to the hole 1422.In some embodiments, the lift plate 1522A may be configured to be secured to two or more three dimensional structural frames, such as twelve three dimensional structural frames.\",\n \"For instance, hardware may engage the first series of a pattern of mounting holes 1526A and through holes of the three dimensional structural frames, such as through holes 1012B and 1012C.\",\n \"In some embodiments, the hardware may include fasteners, such as bolts and rivet nuts.\",\n \"With this arrangement, one four-through-hole pattern of the first series of a pattern of mounting holes 1526A may correspond to through holes of a three dimensional structural frame, such as through holes 1012B and 1012C.\",\n \"Lift plates 1522B-E may be configured to be secured to three dimensional structural frames in the same or similar way that the lift plate 1522A is configured to be secured to three dimensional structural frames.\",\n \"Further, the liftable enclosure 1500 includes opposing walls 1530 interconnected by the plurality of three dimensional structural frames 1510, wherein the walls 1530 comprise a plurality of uniform wall sections 1540.In the illustrated example, wall section 1540A includes a wall panel portion 1542A, a top wall portion 1544A, and sidewall portions 1546A and 1548A.\",\n \"With this arrangement, the sidewall portions of the plurality of wall sections 1540 are connected to form at least a portion of a wall of the enclosure 1500, where the plurality of three dimensional structural frames 1510 are attached to the top wall portions of the wall sections 1540.In some embodiments, the lift plates 1520 may be connected to the wall panel portions of the wall sections.\",\n \"The wall panel portion 1542A may take the form of or be similar in form to the wall panel portion 910, the top wall portion 1544A may take the form of or be similar in form to the top wall portion 920, and sidewall portions 1546A and 1548A may take the form of or be similar in form to the sidewall portions 930A and 930B.\",\n \"In some embodiments, the lift plate 1522A may be configured to be secured to two or more wall sections, such as four wall sections.\",\n \"For instance, hardware may engage the second series of a pattern of mounting holes 1527A and through holes of the wall sections, such as through holes 1032A-D.\",\n \"In some embodiments, the hardware may include fasteners, such as bolts and rivet nuts.\",\n \"Further, in some embodiments, when the liftable enclosure 1500 includes a roof with a weatherproof membrane, such as the weatherproof membranes 1130A and 1130B, hardware may engage the series of pattern of mounting holes, through holes of the three dimensional structural frame members, and through holes of the wall sections after the weatherproof membrane is secured to the three dimensional structural frame members and walls sections.\",\n \"And in some such embodiments, the weatherproof membrane is secured to the three dimensional structural frame members via the through holes of the three dimensional structural frame members and via the through holes of the wall sections.\",\n \"Further still, in some embodiments, using the at least two lift plates 1520 to lift the liftable enclosure 1500 may reduce damage to the enclosure after or while the enclosure is lifted.\",\n \"Moreover, in some embodiments, the enclosure 1500 may be designed to withstand loads caused by wind that has a speed of 150 miles per hour.\",\n \"III.\",\n \"Example Methods FIG.\",\n \"16 shows a method 1600 for building an enclosure, according to an example embodiment.\",\n \"Method 1600 begins at block 1602 with fabricating opposing walls of the enclosure by attaching sidewall portions of a plurality of wall sections comprising a wall panel portion, a top wall portion, and sidewall portions, wherein the sidewall portions of the plurality of wall portions are connected to form at least a portion of a wall of the enclosure.\",\n \"The opposing walls may take the form of or be similar in form to the opposing walls 820, opposing walls 1220, and/or the opposing walls 1530; and the wall sections may each take the form of or be similar in form to the wall section 900.Method 1600 continues at block 1604 with attaching a plurality of three dimensional structural frames to the top wall portions of the wall sections of the opposing walls.\",\n \"The plurality of three dimensional structural frames may take the form of or be similar in form to the plurality of three dimensional structural frames 810, the plurality of three dimensional structural frames 1210, and/or the plurality of three dimensional structural frames 1510.In some embodiments, the opposing walls are fabricated while the sidewall portions are substantially horizontal.\",\n \"The term “substantially horizontal,” as used in this disclosure, means exactly horizontal or one or more deviations from exactly horizontal that do not significantly impact lifting enclosures described herein.\",\n \"Moreover, in some embodiments, the opposing walls are uprighted by attaching a lift plate to a top end of a plurality of wall sections and lifting the top end.\",\n \"The lift plate may take the form of or be similar in form to the lift plate 1300 and/or the lift plate 1400.FIG.\",\n \"17 shows a method 1700 for lifting an enclosure, such as the enclosure 800 and/or the enclosure 1300, according to an example embodiment.\",\n \"Method 1700 begins at block 1702 with attaching a plurality of lift plates to a plurality of the ends of the three dimensional structural frames and wall panels sections of the opposing walls.\",\n \"Further, method 1700 continues at block 1704 with attaching a harness to the plurality of lift plates.\",\n \"And method continues at block 1706 with lifting the enclosure with an upward force to the harness.\",\n \"In some embodiments, the lift plates comprise (i) a planar portion comprising a series of a pattern of mounting holes for receiving hardware for securing the plate to the ends of the plurality of frames and the wall panel sections, and (ii) a connecting portion for attaching the harness.\",\n \"The lift plates may take the form of or be similar in form to the lift plate 1300 and/or the lift plate 1400.Moreover, in some embodiments, the harness may be attached to the plurality of lift plates via a hole in the lift plates, such as the hole 1322 and/or the hole 1422.IV.\",\n \"Conclusion Examples given above are merely illustrative and are not meant to be an exhaustive list of all possible embodiments, applications or modifications of the invention.\",\n \"Thus, various modifications and variations of the described methods and systems of the invention will be apparent to those skilled in the art without departing from the scope and spirit of the invention.\",\n \"Although the invention has been described in connection with specific embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments.\",\n \"Indeed, various modifications of the described modes for carrying out the invention which are obvious to the skilled artisan.\",\n \"It is understood that the invention is not limited to the particular methodology, protocols, etc., described herein, as these may vary as the skilled artisan will recognize.\",\n \"It is also to be understood that the terminology used herein is used for the purpose of describing particular embodiments only, and is not intended to limit the scope of the invention.\",\n \"It also is to be noted that, as used herein and in the appended claims, the singular forms “a,” “an,” and “the” include the plural reference unless the context clearly dictates otherwise.\",\n \"Thus, for example, a reference to “a three dimensional structural frame” is a reference to one or more three dimensional structural frames and equivalents thereof known to those skilled in the art.\",\n \"Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art to which the invention pertains.\",\n \"The embodiments of the invention and the various features and advantageous details thereof are explained more fully with reference to the non-limiting embodiments and/or illustrated in the accompanying drawings and detailed in the following description.\",\n \"It should be noted that the features illustrated in the drawings are not necessarily drawn to scale, and features of one embodiment may be employed with other embodiments as the skilled artisan would recognize, even if not explicitly stated herein.\",\n \"Any numerical values recited herein include all values from the lower value to the upper value in increments of one unit provided that there is a separation of at least two units between any lower value and any higher value.\",\n \"As an example, if it is stated that the concentration of a component or value of a process variable such as, for example, size, angle size, pressure, time and the like, is, for example, from 1 to 90, specifically from 20 to 80, more specifically from 30 to 70, it is intended that values such as 15 to 85, 22 to 68, 43 to 51, 30 to 32, etc.\",\n \"are expressly enumerated in this specification.\",\n \"For values which are less than one, one unit is considered to be 0.0001, 0.001, 0.01 or 0.1 as appropriate.\",\n \"These are only examples of what is specifically intended and all possible combinations of numerical values between the lowest value and the highest value enumerated are to be considered to be expressly stated in this application in a similar manner.\",\n \"Particular methods, devices, and materials are described, although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the invention.\",\n \"The disclosures of all references and publications cited above are expressly incorporated by reference in their entireties to the same extent as if each were incorporated by reference individually.\"\n ]\n]"},"source":{"kind":"string","value":"Patent_15871940"}}},{"rowIdx":4493962,"cells":{"text":{"kind":"list like","value":[["Exercise Machine Reversible Resistance System","An exercise machine reversible resistance system for reversing the directional force of resistance against an exercise implement before, during, or after the performance of a routine of one or more exercises.","The exercise machine reversible resistance system generally includes a frame, an elongated member movably positioned upon the frame, wherein the elongated member has a first run and a second run, a resistance device that applies a resistance force to the elongated member in a single direction, an exercise implement movably connected to the frame and a clutch connected to the exercise implement.","The clutch is adapted to selectively engage the first run or the second run of the elongated member for selective control of the resistance direction of the exercise implement."],["1.An exercise machine, comprising: a frame having a first end, a second end, and a first rail; a carriage slidably positioned upon the first rail of the frame, wherein the carriage is slidable along a longitudinal axis of the frame between the first end and the second end of the frame; an elongated member movably positioned upon the frame, wherein the elongated member has a first run and a second run, wherein when the first run moves in a first direction the second run moves in a second direction that is substantially opposite of the first direction, and wherein when the first run moves in the second direction the second run moves in the first direction; a resistance device connected to the elongated member, wherein the resistance device applies a resistance force to the elongated member and the carriage in the second direction relative to the first run and wherein the resistance device applies the resistance force to the elongated member and the carriage in the first direction relative to the second run; and a clutch connected to the carriage, wherein the clutch includes an engagement portion having a first end and a second end, wherein the first end is adapted to selectively engage the first run and the second end is opposite of the first end and adapted to selectively engage the second run of the elongated member, such that the carriage is configured to provide the resistance force to an exerciser in the second direction when the clutch is engaged to the first run, and the carriage is configured to provide the resistance force to an exerciser in the first direction when the clutch is engaged to the second run.","2.The exercise machine of claim 1, wherein the first run and the second run are substantially parallel with respect to one another.","3.The exercise machine of claim 2, wherein the first run is positioned above the second run.","4.The exercise machine of claim 2, wherein the first run is positioned to a side of the second run.","5.The exercise machine of claim 1, wherein the first run and the second run are horizontally aligned.","6.The exercise machine of claim 1, wherein the first run and the second run are vertically aligned.","7.The exercise machine of claim 1, wherein the clutch is comprised of a linear clutch.","8.The exercise machine of claim 1, wherein the elongated member is comprised of an endless loop structure.","9.The exercise machine of claim 8, including a first wheel rotatably connected to the frame and a second wheel rotatably connected to the frame, wherein the elongated member is movably positioned upon the first wheel and the second wheel, wherein the first run and the second run are positioned between the first wheel and the second wheel.","10.The exercise machine of claim 9, wherein the elongated member includes a plurality of teeth selectively engageable by the clutch.","11.The exercise machine of claim 10, wherein the plurality of teeth extend inwardly.","12.The exercise machine of claim 11, wherein the elongated member is comprised of a belt.","13.The exercise machine of claim 12, wherein the resistance device is connected to the first wheel to apply the resistance force against rotation of the first wheel in a first rotational direction.","14.The exercise machine of claim 1, wherein the resistance device is comprised of a bias member.","15.The exercise machine of claim 14, wherein the bias member is elongated and resilient.","16.The exercise machine of claim 15, wherein the bias member is comprised of a spring.","17.The exercise machine of claim 1, wherein the elongated member is comprised of a chain.","18.The exercise machine of claim 1, wherein the clutch includes an actuator connected to the engagement portion and adapted to linearly translate the engagement portion to a retracted position and an extended position, wherein the first end of the engagement portion engages the first run in the retracted position, and the second end of the engagement portion engages the second run in the extended position.","19.The exercise machine of claim 1, including: a first end platform connected to the frame, wherein the first end platform is near the first end of the frame; and a second end platform connected to the frame, wherein the second end platform is near the second end of the frame.","20.The exercise machine of claim 1, wherein the frame includes a second rail, wherein the second rail is parallel with respect to the first rail, and wherein the carriage is movably positioned upon the first rail and the second rail.","21.An exercise machine, comprising: a frame having a first end, a second end, and a first rail; a first end platform connected to the frame, wherein the first end platform is near the first end of the frame; a carriage slidably positioned upon the first rail of the frame, wherein the carriage is slidable along a longitudinal axis of the frame between the first end and the second end of the frame; an elongated member movably positioned upon the frame, wherein the elongated member is comprised of an endless loop structure, wherein the elongated member has a first run and a second run, wherein when the first run moves in a first direction the second run moves in a second direction that is substantially opposite of the first direction, wherein when the first run moves in the second direction the second run moves in the first direction, wherein the first run and the second run are substantially parallel with respect to one another, and wherein the first run and the second run are horizontally aligned; a resistance device connected to the elongated member, wherein the resistance device applies a resistance force to the elongated member and the carriage in the second direction relative to the first run and wherein the resistance device applies the resistance force to the elongated member and the carriage in the first direction relative to the second run; and a clutch connected to the carriage, wherein the clutch includes an engagement portion having a first end and a second end, wherein the first end is adapted to selectively engage the first run and the second end is opposite of the first end and adapted to selectively engage the second run of the elongated member, such that the carriage is configured to provide the resistance force to an exerciser in the second direction when the clutch is engaged to the first run, and the carriage is configured to provide the resistance force to an exerciser in the first direction when the clutch is engaged to the second run.","22.The exercise machine of claim 21, wherein the frame includes a second rail, wherein the second rail is parallel with respect to the first rail, and wherein the carriage is movably positioned upon the first rail and the second rail.","23.The exercise machine of claim 22, including a second end platform connected to the frame, wherein the second end platform is near the second end of the frame.","24.An exercise machine, comprising: a frame having a first end, a second end, and a first rail; a first end platform connected to the frame, wherein the first end platform is near the first end of the frame; a second end platform connected to the frame, wherein the second end platform is near the second end of the frame; a second end platform connected to the frame, wherein the second end platform is near the second end of the frame; a carriage slidably positioned upon the first rail of the frame, wherein the carriage is slidable along a longitudinal axis of the frame between the first end and the second end of the frame; an elongated member movably positioned upon the frame, wherein the elongated member is comprised of an endless loop structure, wherein the elongated member has a first run and a second run, wherein when the first run moves in a first direction the second run moves in a second direction that is substantially opposite of the first direction, wherein when the first run moves in the second direction the second run moves in the first direction, wherein the first run and the second run are substantially parallel with respect to one another, and wherein the first run and the second run are horizontally aligned; a first wheel rotatably connected to the frame and a second wheel rotatably connected to the frame, wherein the elongated member is movably positioned upon the first wheel and the second wheel, wherein the first run and the second run are positioned between the first wheel and the second wheel; a resistance device connected to the elongated member, wherein the resistance device applies a resistance force to the elongated member and the carriage in the second direction relative to the first run and wherein the resistance device applies the resistance force to the elongated member and the carriage in the first direction relative to the second run; and a clutch connected to the carriage, wherein the clutch includes an engagement portion having a first end and a second end, wherein the first end is adapted to selectively engage the first run and the second end is opposite of the first end and adapted to selectively engage the second run of the elongated member, such that the carriage is configured to provide the resistance force to an exerciser in the second direction when the clutch is engaged to the first run, and the carriage is configured to provide the resistance force to an exerciser in the first direction when the clutch is engaged to the second run.","25.The exercise machine of claim 24, wherein the frame includes a second rail, wherein the second rail is parallel with respect to the first rail, and wherein the carriage is movably positioned upon the first rail and the second rail."],[" BACKGROUND OF THE INVENTION "],[" BRIEF SUMMARY OF THE INVENTION Provided herein is an exercise machine reversible resistance system which includes an exercise machine which has a movable exercise implement.","The exercise implement is adapted to move with a drive belt which is connected at one end to a drive pulley and at the other end to an idler pulley.","The exercise implement includes a clutch which selectively engages with different positions on the inner surface of the drive belt to adjust a direction of resistance applied against movement of the exercise implement.","The clutch is movable between three positions: a first position in which the clutch is disengaged and no resistance is applied against the exercise implement, a second position in which the clutch is engaged with a first portion of the drive belt and resistance is applied against movement of the exercise implement in a first direction, and a third position in which the clutch is engaged with a second portion of the drive belt and resistance is applied against movement of the exercise implement in a second direction.","There has thus been outlined, rather broadly, some of the features of the invention in order that the detailed description thereof may be better understood, and in order that the present contribution to the art may be better appreciated.","There are additional features of the invention that will be described hereinafter and that will form the subject matter of the claims appended hereto.","In this respect, before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not limited in its application to the details of construction or to the arrangements of the components set forth in the following description or illustrated in the drawings.","The invention is capable of other embodiments and of being practiced and carried out in various ways.","Also, it is to be understood that the phraseology and terminology employed herein are for the purpose of the description and should not be regarded as limiting."],["CROSS REFERENCE TO RELATED APPLICATIONS The present application is a continuation of U.S. application Ser.","No.","14/840,910 filed on Aug. 31, 2015 (Docket No.","LAGR-055), which claims priority to U.S.","Provisional Application No.","62/043,503 filed Aug. 29, 2014 (Docket No.","LAGR-038).","Each of the aforementioned patent applications, and any applications related thereto, is herein incorporated by reference in their entirety.","STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT Not applicable to this application.","BACKGROUND OF THE INVENTION Field of the Invention The present invention relates generally to an exercise machine and more specifically it relates to an exercise machine reversible resistance system for reversing the directional force of resistance against an exercise implement before, during, or after the performance of a routine of one or more exercises.","Description of the Related Art Any discussion of the related art throughout the specification should in no way be considered as an admission that such related art is widely known or forms part of common general knowledge in the field.","Exercise is human physical activity that enhances or maintains overall physical health of an exerciser.","Exercise is performed to increase muscle strength, improve balance, improve cardiovascular efficiency, and to aid in weight loss.","Cardiovascular exercises are intended to improve circulatory and respiratory performance and health by raising the heart rate for an extended period of time, increasing oxygenation and calorie burn.","Within the fitness industry, cardiovascular exercise as often referred to as “cardio”.","Typical cardio exercise equipment found in gyms includes treadmills, stationary bikes, elliptical trainers, and stair climbers.","Cardio exercises performed without the aid of specialized apparatuses include running and swimming.","Strength exercises are intended to increase the ability for muscles to perform more work.","The exercises are practiced consistently over weeks or months.","Strength exercises are typically performed in short but high intensity muscle bursts, rather than the long duration of cardio exercises.","Strength training is intended to break down the muscles targeted by the exercise.","The subsequent repair of muscle tissue after training is achieved by increased localized blood circulation that delivers nutrients and oxygen, both of which promote repair and growth of the muscle beyond its size and strength prior to exercise.","Strength exercise machines are apparatuses or devices providing for fixed or adjustable amounts of resistance, and which are used during physical activity to enhance the strength or conditioning effects of the performed exercises.","Myriad apparatuses have been made available by many manufacturers, each apparatus intended to work one targeted muscle or group of muscles.","For instance, a bicep curl machine is intended to exercise only the bicep muscles, while a chest press machine is intended to primarily exercise the chest muscles, but to a lesser degree, shoulder and triceps muscles.","Strength exercise apparatuses may incorporate as the resistance source free weights, for example, barbells, dumbbells or stacked weights, resistance springs or bands, or position the exerciser so as to use the exerciser's own body weight as the weight resistance source.","Contemporary methods of exercising against a workload are many, and well known to those skilled in the art.","One method of creating a direct vertical workload is an exerciser's application of force to lift a dead weight from a resting position to a higher vertical position.","Another method of creating a horizontal workload is to redirect a vertical workload along a horizontal vector using a pulley or mechanical linkage.","Yet another method of creating a workload in any direction is to apply a force opposite the force axis of a variable resistance means, such as a spring or elastic resistance band.","Still another method of creating a workload is to require a continuous cycle of lifting one's own body weight.","For instance, a person exercising on a motorized treadmill is required to increase or decrease the elevation through which they lift their body with each step, and/or to increase or decrease the speed or length of stride in order to maintain their relatively stationary position upon the moving treadmill belt.","Increasing the pitch of the treadmill belt further causes the exerciser to increase their work by lifting their body weight higher with each step in order to maintain their position on a treadmill.","Those skilled in the art will recognize that most all exercise apparatuses provide for continuous or cyclical exercising in one primary direction.","For instance, an bicep curl machine is operated by an exerciser repeatedly flexing their bicep to raise their lower arm against a prescribed weight, then by slowly releasing the bicep muscle flex, allows the re-extension of their lower arm to return the weight to the starting point, then repeat the cycle for a prescribed number of times.","On the other hand, a triceps apparatus works opposite to a bicep curl apparatus in that the primary work is performed by flexing the triceps to extend the forearm to substantially align with the upper arm while working against a weight or resistance.","By slowly relaxing the triceps, the weight is returned to its starting point as the lower arm assumes a decreasing angle relative to the upper arm.","As can readily be understood in the foregoing descriptions, exercise machines are intended to deliver a workload in one direction only.","The primary work cycle on a bicep machine is achieved when the hand working against the resistance approaches the shoulder, while the primary work cycle on a triceps machine is achieved when the hand working against the resistance moves away from the shoulder.","Therefore, a bicep machine does not appreciably exercise triceps, and a triceps machine does not appreciably exercise the biceps.","Another form of exercise produces a mixed benefit of combining cardio and strength training.","Known to those skilled in the art, circuit training is a form of exercise that requires the exerciser to continuously work against resistance for a prolonged period, as previously described in cardio exercises, yet also incorporates a routine of large number of exercises that are performed in a rapid sequence, without any appreciable rest between each exercise.","One variation of circuit training is sometimes referred to as interval training wherein the exerciser generally performs the same exercise for a period of specific duration, similar to cardio exercising, but varies the resistance level throughout the routine period to substantially increase the exerciser's workload for short duration, high intensity bursts, then decrease the workload during a moderate recovery period whereby the cardio exercise intensity is maintained until a subsequent burst.","The exerciser repeats this high/low intensity cycle until the end of the training period.","A disadvantage of attempting to perform circuit or interval training on a variety of exercise apparatuses by immediately and without an appreciable rest period, moving from one apparatus for one exercise, to another apparatus for a subsequent exercise is that in a typical gym environment, there will be another exerciser already working out on the next apparatus in the sequence, forcing the circuit exerciser to wait until the apparatus is available.","This breaks the intended benefits of the continuous cycle of circuit training.","Another disadvantage of performing circuit training using multiple apparatuses in sequence within a gym environment is that even if the next apparatus is vacant, the proper weight, resistance level, or direction of resistance must be re-set for each exerciser.","In many instances, this is time consuming, confusing, and the proper weight setting cannot be readily determined.","Again, the break in the circuit sequence reduces the intended advantages of the circuit training session.","A disadvantage of attempting to perform a variation of circuit training upon a single exercise apparatus is that an exerciser must stop the exercise routine, most often by having to dismount the apparatus in order to change the existing resistance settings to new settings or to reverse the direction of resistance.","The exerciser then re-mounts the apparatus and re-establishes proper positioning before continuing a new exercise at the new resistance setting.","However, after a short period of performing a first exercise, often merely a minute or two, the exerciser would have to again dismount and change the resistance settings or the direction of resistance for a second exercise—then repeat the entire process with many additional exercises included in the particular routine.","It often takes more time to change the resistance settings than the period of time the exerciser will actually perform the new exercise at the new setting.","Still another disadvantage of all of the exercise machines and Pilates apparatuses just described is that the resistance is unidirectional.","In other words, none of the machines provide for an exerciser to immediately change the direction of the resistance force.","As an example, the rotating belt of a motorized treadmill is intended to move such that an exerciser, facing the front of the machine, can walk or run at different speeds, on a flat, or “uphill”.","Reversing the rotation of the rotating belt would require the exerciser to begin walking or running backwards, and possibly “downhill”.","Not only would this be an unnatural exercise, reversing a treadmill belt during exercise would be dangerous, and would likely be the source of many injuries.","As another example, a pull down machine to exercise the latissimus dorsi muscles provides a seat upon which an exerciser sits, and an overhead bar attached to a cable.","The cable is threaded through a pulley on the machine, and is attached to weights.","When an exerciser pulls down the overhead bar to work the latissimus dorsi or back muscles, the downward direction of their pull is reversed through the pulley, and they are actually pulling the weights that are attached to the cable upward from the floor.","On the other hand, there is no provision to allow the exerciser to switch resistance direction so they can push upward on the bar and lift the weights to exercise the shoulders as would be provided by a shoulder press machine.","Pushing upward provides no work resistance.","Yet another exemplary embodiment of the present invention is an improved exercise apparatus with a force reversing system providing for a plurality of exercise resistance springs affixed to an apparatus structure, a means providing for an exerciser to input an exercising force in one moveable direction sufficient to overcome one or more of the resistance springs, and a system providing for an exerciser to immediately reverse the direction of motion against which a counteracting resistance force will be applied.","For instance, an exerciser's upward force movement as required to work against the spring resistance can be reversed to a downward force required to work against the spring resistance.","Another object of the present invention is an improved Pilates apparatus comprising a substantially longitudinal frame, an idler pulley affixed at substantially one end of the apparatus, a driven pulley on a drive shaft affixed at substantially the opposed end of the apparatus, a drive belt affixed to at least the idler and driven pulleys, and therebetween, an exercise carriage slidable along the longitudinal axis of the apparatus, the carriage being optionally engageable along the length of either side of the drive belt, thereby allowing an exerciser to select which direction the slidable carriage and correspondingly, the rotational direction of the driven pulley will move responsive to an exercise force input exerted upon the slidable platform.","The reverser as currently illustrated is ‘self energizing’.","This means that the more force an exerciser applies to the platform, pull the harder it tries to engage.","A beneficial side effect is that if the exerciser pushes the rollable platform in the wrong direction, it disengages, thus preventing the platform back driving the spring mechanism.","Those skilled in the art will immediately recognize the deficiencies just described, and will understand that a sufficiently large number of machines to allow exercising of each major muscle group housing many machines requires leasing a large and expansive area for a functional gym or Pilates studio.","They will appreciate that one machine capable of providing resistance for a wide variety of exercises allows for more economically efficient operations.","Further, fitness experts and gym operations will appreciate the commercial advantages of a new and improved exercise apparatus that provides for immediate and precise changing of the resistance level without considerable interruption to a workout routine, and a system of immediately reversing the direction of resistance to increase the number of muscles and muscle groups that may be exercised without dismounting the apparatus, thereby obviating the need to make complicated changeovers to the apparatus, or to move to another machine to perform a different exercise.","Because of the inherent problems with the related art, there is a need for a new and improved exercise machine reversible resistance system for reversing the directional force of resistance against an exercise implement before, during, or after the performance of a routine of one or more exercises.","BRIEF SUMMARY OF THE INVENTION Provided herein is an exercise machine reversible resistance system which includes an exercise machine which has a movable exercise implement.","The exercise implement is adapted to move with a drive belt which is connected at one end to a drive pulley and at the other end to an idler pulley.","The exercise implement includes a clutch which selectively engages with different positions on the inner surface of the drive belt to adjust a direction of resistance applied against movement of the exercise implement.","The clutch is movable between three positions: a first position in which the clutch is disengaged and no resistance is applied against the exercise implement, a second position in which the clutch is engaged with a first portion of the drive belt and resistance is applied against movement of the exercise implement in a first direction, and a third position in which the clutch is engaged with a second portion of the drive belt and resistance is applied against movement of the exercise implement in a second direction.","There has thus been outlined, rather broadly, some of the features of the invention in order that the detailed description thereof may be better understood, and in order that the present contribution to the art may be better appreciated.","There are additional features of the invention that will be described hereinafter and that will form the subject matter of the claims appended hereto.","In this respect, before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not limited in its application to the details of construction or to the arrangements of the components set forth in the following description or illustrated in the drawings.","The invention is capable of other embodiments and of being practiced and carried out in various ways.","Also, it is to be understood that the phraseology and terminology employed herein are for the purpose of the description and should not be regarded as limiting.","BRIEF DESCRIPTION OF THE DRAWINGS Various other objects, features and attendant advantages of the present invention will become fully appreciated as the same becomes better understood when considered in conjunction with the accompanying drawings, in which like reference characters designate the same or similar parts throughout the several views, and wherein: FIG.","1 is an upper perspective view of an exemplary embodiment of the present invention.","FIG.","2 is a side sectional view of a horizontal embodiment of the present invention in a first configuration.","FIG.","3 is a side sectional view of a horizontal embodiment of the present invention in a second configuration.","FIG.","4 is a side sectional view of a vertical embodiment of the present invention in a first configuration.","FIG.","5 is a side sectional view of a vertical embodiment of the present invention in a second configuration.","FIG.","6 is an upper perspective view of an additional exemplary embodiment of the present invention in which the elongated member is a chain.","DETAILED DESCRIPTION OF THE INVENTION Various aspects of specific embodiments are disclosed in the following description and related drawings.","Alternate embodiments may be devised without departing from the spirit or the scope of the present disclosure.","Additionally, well-known elements of exemplary embodiments will not be described in detail or will be omitted so as not to obscure relevant details.","Further, to facilitate an understanding of the description, a discussion of several terms used herein follows.","The word “exemplary” is used herein to mean “serving as an example, instance, or illustration.” Any embodiment described herein as “exemplary” is not necessarily to be construed as preferred or advantageous over other embodiments.","Likewise, the term “embodiments” is not exhaustive and does not require that all embodiments include the discussed feature, advantage or mode of operation.","Turning now descriptively to the drawings, in which similar reference characters denote similar elements throughout the several views, FIGS.","1 through 5 illustrate an exercise machine reversible resistance system 10, which comprises a frame 23 having a first end and a second end, an elongated member 31 movably positioned upon the frame 23, a resistance device 52 connected to the elongated member 31, an exercise implement 26 movably connected to the frame 23, and a clutch 60 connected to the exercise implement 26.The elongated member 31 has a first run 31a and a second run 31b between the first end and the second end of the frame as illustrated in FIGS.","1 through 5.When the first run 31a moves in a first direction the second run 31b moves in a second direction that is substantially opposite of the first direction and when the first run 31a moves in the second direction the second run 31b moves in the first direction.","The resistance device 52 applies a resistance force to the elongated member 31 in the second direction relative to the first run 31a and applies the resistance force to the elongated member 31 in the first direction relative to the second run 31b.","The clutch 60 is adapted to selectively engage the first run 31a or the second run 31b of the elongated member 31.The exercise implement 26 receives the resistance force in the second direction when the clutch 60 is engaged to the first run 31a as shown in FIGS.","1, 2 and 4 of the drawings.","The exercise implement 26 receives the resistance force in the first direction when the clutch 60 is engaged to the second run 31b as shown in FIGS.","3 and 5 of the drawings.","The clutch 60 is preferably comprised of a linear clutch to move in a linear manner.","The first run 31a and the second run 31b are preferably substantially parallel with respect to one another as illustrated in FIGS.","1 through 5.The first run 31a and the second run 31b may be horizontally aligned (FIGS.","1 through 3), vertically aligned (FIGS.","4, 5) or aligned at an angle between horizontal and vertical.","The first run 31a may be positioned above, below, to the left or to the right of the second run 31b.","The first run 31a is distally spaced apart from the second run 31b.","The elongated member 31 is comprised of an endless loop structure that rotates around a first wheel 30 and a second wheel 35.The first wheel 30 is rotatably connected to the frame 23 and the second wheel 35 is rotatably connected to the frame 23 distally spaced from the first wheel 30 as illustrated in FIGS.","1 through 5 of the drawings.","The elongated member 31 is movably positioned upon the first wheel 30 and the second wheel 35, wherein the first run 31a and the second run 31b are positioned between the first wheel 30 and the second wheel 35.The elongated member 31 preferably includes a plurality of teeth 32 that are selectively engageable by the clutch 60.The plurality of teeth 32 preferably extend inwardly toward one another between the two opposing runs 31a, 31b as illustrated in FIGS.","1 through 5 of the drawings.","The elongated member 31 may be comprised of a belt, chain or other elongated structure.","The elongated member 31 is preferably comprised of a non-stretchable material.","The resistance device 52 may be directly connected to the elongated member 31 or indirectly connected to the elongated member 31.For example, the resistance device 52 may be connected to the first wheel 30 to apply the resistance force against rotation of the first wheel 30 in a first rotational direction.","The resistance device 52 may be comprised of a bias member that is elongated and resilient (e.g.","elastic member, spring).","The clutch 60 is comprised of an actuator 70 and an engagement portion 64 extending from the actuator 70.The actuator 70 may be comprised of a manually operated actuator (e.g.","a lever) or a powered actuator (e.g.","electric motorized actuator).","The engagement portion 64 has a retracted position for engaging the first run 31a as shown in FIGS.","1, 2, 4 of the drawings.","The engagement portion 64 of the clutch 60 also preferably has an extended position for engaging the second run 31b as shown in FIGS.","3, 5 of the drawings.","The invention in one embodiment is comprised of a frame 23 to which are connected a first wheel 30 and a second wheel 35.The first wheel 30 and second wheel 35 will generally be spaced-apart, though the distance by which they are separated will vary in different embodiments of the present invention.","In the embodiment shown in the figures, the first wheel 30 is positioned at or near the first end 21 of the exercise machine 20 and the second wheel 35 is positioned at or near the second end 22 of the exercise machine 20.An elongated member 31 is shown as connecting the first wheel 30 with the second wheel 35 such that rotation of the first wheel 30 will similarly rotate the freely-rotatable second wheel 35.The first wheel 30 includes a first run 31a and a second run 31b.","It is noted that the particular locations along the inner surface of the elongated member 31 which comprise the first run 31a and second run 31b will vary as the elongated member 31 traverses the path between the first wheel 30 and second wheel 35.Thus, the same location on the inner surface of the elongated member 31 which comprises a first run 31a will comprise the second run 31b of the elongated member 31 at a different time depending on positioning of the elongated member 31 on the first wheel 30 and second wheel 35 at that particular time.","The elongated member 31 of the present invention may comprise various configurations, and should not be construed as limited by the exemplary figures.","In a preferred embodiment as shown in the figures, the elongated member 31 comprises a belt having a plurality of teeth 32 extending along its inner surface.","In other embodiments, the elongated member 31 could comprise a chain with a plurality of links, rather than teeth 32.In other embodiments, the elongated member 31 could comprise a flat surface without any projections such as teeth 32 as discussed herein.","The exercise machine 20 includes an exercise implement 26 which is freely-movable in at least two directions, such as by being movably connected to a frame 23 or rails 27.The exercise machine 20 may be free-standing, such as through use of support feet 24, or may be connected to another structure, such as in a cantilevered configuration.","A bias member 52 is interconnected with the exercise implement 26 as discussed herein such that the bias member 52 will exert resistance against movement of the exercise implement 26 in multiple directions depending on positioning of a clutch 60.The exercise implement 26 may comprise various structures, devices, and the like, and should not be construed as limited by the exemplary figures herein.","FIGS.","1-3 illustrate an embodiment in which the exercise implement 26 comprises a movable carriage.","FIGS.","4-5 illustrate an embodiment in which the exercise implement 26 comprises a handle 25.Various other types of exercise implements 26 may be utilized.","The clutch 60 of the present invention extends from the exercise implement 26; with the clutch 60 being movably connected to the exercise implement 26 in some embodiments.","The clutch 60 is adapted to selectively engage with the first run 31a of the elongated member 31 to apply resistance against movement of the exercise implement 26 in a first direction and to selectively engage with the second run 31b of the elongated member 31 to apply resistance against movement of the exercise implement 26 in a second direction.","Thus, use of the clutch 60 is operable to change the direction of resistance being applied against movement or manipulation of the exercise implement 26.The clutch 60 may comprise various configurations and should not be construed as limited by the exemplary figures.","In the exemplary embodiment shown in the figures, the clutch 60 comprises an extension portion 62 which is connected at a first end to the exercise implement 26 and at a second end to an engagement portion 64.The extension portion 62 may extend vertically downward as shown in the figures, or may extend in different orientations.","The engagement portion 64 is illustrated as extending diagonally with respect to the downwardly-extending extension portion 62, with the first end 65 of the engagement portion 64 being adapted to engage with the first run 31a of the elongated member 31 and the second end 66 of the engagement portion 64 being adapted to engage with the second run 31b of the elongated member 31.The manner in which resistance from the bias member 52 is transferred to be applied against movement of the exercise implement 26 will vary in different embodiments.","One such embodiment is illustrated in the figures; however, the present invention should not be construed as being limited in any respect by the exemplary embodiment.","There are numerous manners in which the resistance force of the bias member 52 may be transferred to be applied against the exercise implement 26.As shown in FIGS.","1-5, one such embodiment comprises the use of gear reduction pulleys 40, 42.In this exemplary embodiment, a first gear reduction pulley 40 shares the same drive shaft 33 as the first wheel 30 such that the first gear reduction pulley 40 and the drive shaft 33 are concentric.","The first gear reduction pulley 40 will generally comprise a smaller diameter than the first wheel 30 as shown in the figures.","A second gear reduction pulley 42 is connected to the exercise machine 20, such as its frame 23, by a gear reduction shaft 44.The first gear reduction pulley 40 is connected to the second gear reduction pulley 42 by a gear reduction belt 43 such that the first and second gear reduction pulleys 40, 42 rotate together.","In the embodiment shown in the figures, the second gear reduction pulley 42 is larger in diameter than the first gear reduction pulley 40.A separate resistance pulley 56 is illustrated as sharing the same gear reduction shaft 44 as the second gear reduction pulley 42, with the resistance pulley 56 being concentric with the second gear reduction pulley 42.The resistance pulley 56 may comprise a smaller diameter than the first wheel 30 as shown in the figures.","The resistance pulley 56 and second gear reduction pulley 42 may comprise substantially the same diameter as shown in the figures, or may comprise different diameters.","The resistance pulley 56 is interconnected with the bias member 52 of the present invention.","In some embodiments, the bias member 52 may be directly connected to the resistance pulley 56.In other embodiments, a separate bias connector 50 may be provided which connects between the bias member 52 and the resistance pulley 56.As shown in the figures, one embodiment of the bias connector 50 is comprised of a cable, with the cable being connected at one end to the resistance pulley 56 and at the other end to the bias member 52.The bias member 52 may comprise various structures known to exert resistance, such as a spring as shown in the figures.","To maintain tension on the drive belt 30, a tensioner pulley 38 may be provided which exerts force against the drive belt 30 to maintain its tension as shown in the figures.","The tensioner pulley 38 may be located anywhere along the length of the drive belt 30, including embodiments which exert tension against the upper portion of the drive belt 30 and embodiments (such as shown in the figures) which exert tension against the lower portion of the drive belt 30.The tensioner pulley 38 will preferably be mounted on its own tensioner shaft 39; with the tensioner shaft 39 being connected to the exercise machine 20, such as to its frame 23.The exercise machine reversible resistance system 10 is adapted to transition between a push-force configuration shown in FIGS.","2 and 4, in which the exercise implement 26 is resisted as it is moved in a first direction FE1, and a pull-force configuration shown in FIGS.","3 and 5, in which the exercise implement 26 is resisted as it is moved in a second direction FE2.As illustrated throughout the figures, the first direction FE1 is opposite with respect to the second direction FE2.FIG.","1 is an exemplary upper perspective view of the present invention.","While this figure illustrates the exercise machine 20 as comprising a Pilates machine configuration, various types of other exercise machines 20 may be utilized as discussed herein.","An exercise implement 26 is provided as part of the exercise machine 20, and may be connected to any portion of the exercise machine 20.The positioning of the exercise implement 26 will vary depending on the type of exercise machine 20 being utilized.","Any type of exercise machine 20 which utilizes an exercise implement 26 and bias members 52, such as rowing machines, weight lifting machines, universal exercise machines, press machines, squat machines, curl machines, triceps machines, dip machines, elliptical trainers, and the like.","Thus, the present invention should not be construed as being limited to any particular type of exercise machine 20 or exercise implement 26.By way of example, FIGS.","1-3 illustrate the present invention being utilized in combination with a Pilates machine.","As an additional example, FIGS.","4-5 illustrate the present invention being utilized in combination with an exercise machine 20 adapted to function as either a curl machine or a triceps machine depending on its configuration.","FIG.","2 is an exemplary diagram showing a side view of an exercise machine reversible resistance system 10 which is in a push-force configuration.","More specifically, in the push-force exercise configuration as shown in FIG.","1, an elongated member 31 is installed around a first wheel 30 and a second wheel 35.The first wheel 30 is affixed to a rotatable drive shaft 33 and the second wheel 35 is affixed to a rotatable idler shaft 36, with the drive shaft 33 and idler shaft 36 being secured to the exercise machine 20, such as to its frame 23.A tensioner pulley 38 is provided as a means to create a preferred tension on the elongated member 31, with the tensioner pulley 38 being affixed to a rotatable tensioner shaft 39.As shown in FIG.","2, a clutch 60 in the “push” position affixed to the exercise implement 26 is selectively engageable with the elongated member 31 such that when an exerciser 12 applies an exercise force FE1 in the direction shown, the exercise implement 26 moves along the length of the exercise machine 20, and the elongated member 31 correspondingly moves in the same direction, for the same length of travel as the exercise implement 26.A first gear reduction pulley 40 is affixed to the same drive shaft 33 as the first wheel 30, with the first gear reduction pulley 40 and the first wheel 30 being concentric.","The first gear reduction pulley 40 is adapted such that the first gear reduction pulley 40 rotates in response to exercise forces exerted upon the elongated member 31.Rotation of the first gear reduction pulley 40 rotates a second gear reduction pulley 42 which is separately connected to a gear reduction shaft 44; with the first gear reduction pulley 40 and the second gear reduction pulley 42 being interconnected by a gear reduction drive belt 43, thereby reducing the angle of rotation of the a resistance pulley 56 connected to the same gear reduction shaft 44 relative to the first gear reduction pulley 40.As shown in the figures, the resistance pulley 56 is connected to the gear reduction shaft 44 such that the resistance pulley 56 and the second gear reduction pulley 42 are concentric.","The resistance pulley 56 is preferably of a smaller diameter than the first wheel 30 and a larger diameter than the first gear reduction pulley 40 as shown in the figures.","The bias member 52 is interconnected with the resistance pulley 56 such that resistance force is applied against rotation of the resistance pulley 56 in a first direction.","The bias member 52 may be directly connected to the resistance pulley 56, or may be connected to the resistance pulley 56 by a bias connector 50 such as a cable as shown in the figures.","It is preferable that the first end 53 of the bias members 52, where affixed to a bias connector 50, travel a distance shorter than the measurable travel of the exercise implement 26.The second end 54 of the bias members 52 is attached to the frame 23.More specifically, the use of the gear reduction pulleys 40, 42 just described limits the rotation of the resistance pulley 56 to one revolution relative to the total range of travel of the exercise implement 26, thereby limiting the bias connector 50 or bias member 52 winding about the resistance pulley 56 to one wrap.","It is well known to those skilled in the art that when a cable is wrapped multiple times around itself on a pulley, the effective diameter of the pulley increases, and the force necessary to rotate the pulley increases.","In the exercise machine of the present invention, a constant and predictable linear force against a predetermined resistance force FR is preferred to the requirement of an increasing force to continue rotating the resistance pulley 56.As the second gear reduction pulley 42 is rotated in response to the input exercise force upon the exercise implement 26, the resistance pulley 56 similarly rotates with the same gear reduction shaft 44 such that the bias connector 50 free length shortens, thereby overcoming a predetermined resistance force FR extending one or more of the bias members 52 provided as a means to resist the exercise input force FE1.Oftentimes, it is preferable that an exerciser 12 contracts muscles that pull loads or resistance, rather than contracting opposing muscles that push loads or resistances.","In such situations, an exerciser would shift the clutch from a “push” position as shown in FIGS.","2 and 4 to a “pull” position shown in FIGS.","3 and 5, thereby engaging teeth 32 on the elongated member 31 on the opposite side of the first wheel 30.As can readily be seen in the pull-force exercise configuration shown in the figures, with the clutch 60 engaged in the pull position and disengaged in the push position, the exerciser 12 may immediately begin exerting an exercise force on the exercise implement 26 in the opposite direction FE2, thereby providing for the engagement and exercise of the pulling muscles by directing the force against a resistance force FR.","Those expert in exercise machines 20, and more specifically Pilates apparatuses, will immediately appreciate the benefit of providing the previously unknown system and method of reversing the direction of force that an exercise exerts upon an exercise implement 26, including the ability to change from a pulling exercise to pushing exercise with little or no interruption of the overall exercise routine, and the elimination of the traditional requirement for an exerciser 12 to completely rotate their position upon an exercise machine 20 so that they are facing in a second direction opposite of the first direction so that they can engage a different set of muscles.","Further, they will appreciate that by providing for the reversal of force direction upon the exercise implement 26, the pushing and pulling exercises may be applied to a set of handles 25 at a first end 21 of the exercise machine 20, thereby eliminating the requirement for any handles 25 at the second end 22 of the exercise machine 20.The figures illustrate the elongated member 31 as comprising a belt having a plurality of teeth 32 on its inner circumference.","One of ordinary skill in the art will appreciate that multiple other types of drive connectors 31 may be utilized with the present invention, such as chains and the like.","It should be noted that the preferable use of teeth 32 on the elongated member 31 is not meant to be limiting, flat belts, V-belts, as well as chains delivering the functionality just described may be used without deviating from the novel functionality of the present invention.","Further, the preferred clutch 60 system just described provides for the engagement of gear features of the clutch 60, such as either of the ends 65, 66 of the engaging portion 64 shown in the figures, with teeth 32 on the elongated member 31 is not meant to be limiting, and the alternative methods of engaging a clutch 60 with an elongated member 31 such as a belt may include friction clamps such as a V-grooved plate engageable with a V-belt.","Therefore, many methods of engaging the inside surface of a drive connector are well known, and may be used to accomplish the intended result in the novel, and previously unavailable system and method of the present invention providing for reversibly directing an exerciser's exercise force against one or more springs that provide resistance force FR in only one direction FE1 or FE2.In use, the clutch 60 will generally start in a position in which it is not engaged with any portion of the elongated member 31.In this position, the exercise implement 26 may freely traverse the exercise machine 20 without any resistance from the bias member 52.The exerciser 12 may freely position the exercise implement 26 at the desired location to begin an exercise without any force of resistance being transferred from the bias member 52 while the clutch 60 is disengaged.","Once the exercise implement 26 is located at the desired starting position for exercises, the clutch 60 may be engaged such that the bias member 52 exerts resistance against the exercise implement 26 as it is moved in a first direction FE1.In this case, the clutch 60 may be pulled upwardly such that the first end 65 of the engagement portion 64 of the clutch 60 engages with the first run 31a of the elongated member 31 as shown in FIG.","2.One manner of such engagement is shown in the figures, in which the first end 65 of the engagement portion 64 engages with the teeth 32 on the first run 31a of the first wheel 30.The exerciser 12 may then perform various exercises with the exercise implement 26 being biased against movement in the first direction FE1.Upon completion a first set of exercises, the exerciser 12 may desire to reverse the direction of resistance.","Utilizing the present invention, the exerciser 12 may easily and efficiently reverse the direction of resistance against the exercise implement 26 using only the clutch.","Without getting off the carriage 12 or manipulating any other structure, the exerciser 12 may simply force the clutch 60 downwardly such that the first end 65 of the engagement portion 64 disengages with the first run 31a of the elongated member 31.With continued downward force, the second end 66 of the engagement portion 64 will engage with the second run 31b of the elongated member 31.When so configured, the exercise implement 26 will be resisted against movement in the second direction FE2.The exerciser 12 may then continue with a different set of exercises which utilizes the opposite direction of resistance than the first set of exercises.","The exerciser 12 may repeat these steps repeatedly to perform different sets of exercises against different directions of resistance.","The exerciser 12 may dismount the present invention at any time.","It may be preferable to position the clutch 60 in its disengaged position (i.e.","the engagement portion 64 does not engage with any portion of the elongated member 31) such that the exercise implement 26 is freely movable into any position by a future exerciser 12.FIGS.","4 and 5 are exemplary diagrams showing a side view of the present invention in a vertical orientation.","More specifically, the embodiment of the exercise machine reversible resistance system 10 shown in FIGS.","1-3 is shown rotated so that the longitudinal axis to which a linear exercise force is applied to an exercise implement 26 is tilted so that the exercise force axis is substantially vertical.","Utilizing the same principles as previously described, the present invention provides for a plurality of exercises typically performed while the upper body is substantially vertical.","For instance, those skilled in the art will appreciate that exercise machines 20 referred to as bicep curl machines allow an exerciser 12 to approach the machine, with arms substantially straight and extended grasp a handle 25 serving as an exercise implement 26 with one or both hands, and contract the bicep muscle against a resistance force until the hand is proximal to its respective shoulder.","Thereafter, the exerciser would reverse the action, slowly releasing the bicep contraction, thereby allowing the lower arm to extend back to substantially the starting position.","One advantage of the present invention is that the exercise machine 20 as previously described weighs less than a machine that uses stacked weights.","For example, a plurality of bias members 52, together with an indexable resistance level selector with 15 ten pound increments, would provide a maximum of 150 lbs or resistance force for exercising biceps.","The gross weight of the apparatus that includes the transmission system and bias members 52 would be estimated to weigh 80 pounds, depending on materials construction.","On the other hand, traditional curl machines using similar materials as just described, and that provide 150 pounds maximum resistance force, would necessarily contain a stack of 15 ten pound iron or steel weights, thereby weighing at least 150 pounds.","Therefore, the weight savings which correspond to reduced manufacturing and freight costs, and reduced labor costs for delivering and setting up a curl machine in a gym are all reduced; making the variable transmission system commercially advantageous.","Further, by integrating the reversing clutch 60 system as herein described, the curl machine embodiment of the present invention shown in FIGS.","4-5 can be immediately reversed, thereby becoming a triceps machine wherein an exerciser 12 starts with bent arms, and after grasping the handle 25 which serve as exercise implements 26, may then extend their arms while pushing the handles 25 with a downward force by flexing their triceps.","It is well known that exercisers 12 are advised to exercise counteracting muscles during a workout.","Therefore, triceps and biceps are counteracting muscles, and after completing exercises for one muscle group, the opposing muscle group should be exercised.","Traditional gym machines do not provide for the reversing of the direction of exercise force since they are single exercise/single purpose designed.","The novel function of the present invention provides for one exercise machine 20 that may functionally replace at least two traditional exercise apparatuses.","Therefore, the present invention is more commercially valuable when compared to traditional gym machines in that it provides for significant reduction in the acquisition of equipment needed for a full service gym, and since in many instances, one exercise machine 20 of the present invention can replace the functionality of two machines, allowing a gym to provide the same exercise capacity, but with a substantially reduced facility size.","Although specific embodiments have been illustrated and described herein, it will be appreciated by those of ordinary skill in the art that a wide variety of alternate and/or equivalent implementations may be substituted for the specific embodiments shown and described without departing from the scope of the present disclosure.","This application is intended to cover any adaptations or variations of the embodiments discussed herein.","Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.","Although methods and materials similar to or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described above.","All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety to the extent allowed by applicable law and regulations.","The present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof, and it is therefore desired that the present embodiment be considered in all respects as illustrative and not restrictive.","Any headings utilized within the description are for convenience only and have no legal or limiting effect."]],"string":"[\n [\n \"Exercise Machine Reversible Resistance System\",\n \"An exercise machine reversible resistance system for reversing the directional force of resistance against an exercise implement before, during, or after the performance of a routine of one or more exercises.\",\n \"The exercise machine reversible resistance system generally includes a frame, an elongated member movably positioned upon the frame, wherein the elongated member has a first run and a second run, a resistance device that applies a resistance force to the elongated member in a single direction, an exercise implement movably connected to the frame and a clutch connected to the exercise implement.\",\n \"The clutch is adapted to selectively engage the first run or the second run of the elongated member for selective control of the resistance direction of the exercise implement.\"\n ],\n [\n \"1.An exercise machine, comprising: a frame having a first end, a second end, and a first rail; a carriage slidably positioned upon the first rail of the frame, wherein the carriage is slidable along a longitudinal axis of the frame between the first end and the second end of the frame; an elongated member movably positioned upon the frame, wherein the elongated member has a first run and a second run, wherein when the first run moves in a first direction the second run moves in a second direction that is substantially opposite of the first direction, and wherein when the first run moves in the second direction the second run moves in the first direction; a resistance device connected to the elongated member, wherein the resistance device applies a resistance force to the elongated member and the carriage in the second direction relative to the first run and wherein the resistance device applies the resistance force to the elongated member and the carriage in the first direction relative to the second run; and a clutch connected to the carriage, wherein the clutch includes an engagement portion having a first end and a second end, wherein the first end is adapted to selectively engage the first run and the second end is opposite of the first end and adapted to selectively engage the second run of the elongated member, such that the carriage is configured to provide the resistance force to an exerciser in the second direction when the clutch is engaged to the first run, and the carriage is configured to provide the resistance force to an exerciser in the first direction when the clutch is engaged to the second run.\",\n \"2.The exercise machine of claim 1, wherein the first run and the second run are substantially parallel with respect to one another.\",\n \"3.The exercise machine of claim 2, wherein the first run is positioned above the second run.\",\n \"4.The exercise machine of claim 2, wherein the first run is positioned to a side of the second run.\",\n \"5.The exercise machine of claim 1, wherein the first run and the second run are horizontally aligned.\",\n \"6.The exercise machine of claim 1, wherein the first run and the second run are vertically aligned.\",\n \"7.The exercise machine of claim 1, wherein the clutch is comprised of a linear clutch.\",\n \"8.The exercise machine of claim 1, wherein the elongated member is comprised of an endless loop structure.\",\n \"9.The exercise machine of claim 8, including a first wheel rotatably connected to the frame and a second wheel rotatably connected to the frame, wherein the elongated member is movably positioned upon the first wheel and the second wheel, wherein the first run and the second run are positioned between the first wheel and the second wheel.\",\n \"10.The exercise machine of claim 9, wherein the elongated member includes a plurality of teeth selectively engageable by the clutch.\",\n \"11.The exercise machine of claim 10, wherein the plurality of teeth extend inwardly.\",\n \"12.The exercise machine of claim 11, wherein the elongated member is comprised of a belt.\",\n \"13.The exercise machine of claim 12, wherein the resistance device is connected to the first wheel to apply the resistance force against rotation of the first wheel in a first rotational direction.\",\n \"14.The exercise machine of claim 1, wherein the resistance device is comprised of a bias member.\",\n \"15.The exercise machine of claim 14, wherein the bias member is elongated and resilient.\",\n \"16.The exercise machine of claim 15, wherein the bias member is comprised of a spring.\",\n \"17.The exercise machine of claim 1, wherein the elongated member is comprised of a chain.\",\n \"18.The exercise machine of claim 1, wherein the clutch includes an actuator connected to the engagement portion and adapted to linearly translate the engagement portion to a retracted position and an extended position, wherein the first end of the engagement portion engages the first run in the retracted position, and the second end of the engagement portion engages the second run in the extended position.\",\n \"19.The exercise machine of claim 1, including: a first end platform connected to the frame, wherein the first end platform is near the first end of the frame; and a second end platform connected to the frame, wherein the second end platform is near the second end of the frame.\",\n \"20.The exercise machine of claim 1, wherein the frame includes a second rail, wherein the second rail is parallel with respect to the first rail, and wherein the carriage is movably positioned upon the first rail and the second rail.\",\n \"21.An exercise machine, comprising: a frame having a first end, a second end, and a first rail; a first end platform connected to the frame, wherein the first end platform is near the first end of the frame; a carriage slidably positioned upon the first rail of the frame, wherein the carriage is slidable along a longitudinal axis of the frame between the first end and the second end of the frame; an elongated member movably positioned upon the frame, wherein the elongated member is comprised of an endless loop structure, wherein the elongated member has a first run and a second run, wherein when the first run moves in a first direction the second run moves in a second direction that is substantially opposite of the first direction, wherein when the first run moves in the second direction the second run moves in the first direction, wherein the first run and the second run are substantially parallel with respect to one another, and wherein the first run and the second run are horizontally aligned; a resistance device connected to the elongated member, wherein the resistance device applies a resistance force to the elongated member and the carriage in the second direction relative to the first run and wherein the resistance device applies the resistance force to the elongated member and the carriage in the first direction relative to the second run; and a clutch connected to the carriage, wherein the clutch includes an engagement portion having a first end and a second end, wherein the first end is adapted to selectively engage the first run and the second end is opposite of the first end and adapted to selectively engage the second run of the elongated member, such that the carriage is configured to provide the resistance force to an exerciser in the second direction when the clutch is engaged to the first run, and the carriage is configured to provide the resistance force to an exerciser in the first direction when the clutch is engaged to the second run.\",\n \"22.The exercise machine of claim 21, wherein the frame includes a second rail, wherein the second rail is parallel with respect to the first rail, and wherein the carriage is movably positioned upon the first rail and the second rail.\",\n \"23.The exercise machine of claim 22, including a second end platform connected to the frame, wherein the second end platform is near the second end of the frame.\",\n \"24.An exercise machine, comprising: a frame having a first end, a second end, and a first rail; a first end platform connected to the frame, wherein the first end platform is near the first end of the frame; a second end platform connected to the frame, wherein the second end platform is near the second end of the frame; a second end platform connected to the frame, wherein the second end platform is near the second end of the frame; a carriage slidably positioned upon the first rail of the frame, wherein the carriage is slidable along a longitudinal axis of the frame between the first end and the second end of the frame; an elongated member movably positioned upon the frame, wherein the elongated member is comprised of an endless loop structure, wherein the elongated member has a first run and a second run, wherein when the first run moves in a first direction the second run moves in a second direction that is substantially opposite of the first direction, wherein when the first run moves in the second direction the second run moves in the first direction, wherein the first run and the second run are substantially parallel with respect to one another, and wherein the first run and the second run are horizontally aligned; a first wheel rotatably connected to the frame and a second wheel rotatably connected to the frame, wherein the elongated member is movably positioned upon the first wheel and the second wheel, wherein the first run and the second run are positioned between the first wheel and the second wheel; a resistance device connected to the elongated member, wherein the resistance device applies a resistance force to the elongated member and the carriage in the second direction relative to the first run and wherein the resistance device applies the resistance force to the elongated member and the carriage in the first direction relative to the second run; and a clutch connected to the carriage, wherein the clutch includes an engagement portion having a first end and a second end, wherein the first end is adapted to selectively engage the first run and the second end is opposite of the first end and adapted to selectively engage the second run of the elongated member, such that the carriage is configured to provide the resistance force to an exerciser in the second direction when the clutch is engaged to the first run, and the carriage is configured to provide the resistance force to an exerciser in the first direction when the clutch is engaged to the second run.\",\n \"25.The exercise machine of claim 24, wherein the frame includes a second rail, wherein the second rail is parallel with respect to the first rail, and wherein the carriage is movably positioned upon the first rail and the second rail.\"\n ],\n [\n \" BACKGROUND OF THE INVENTION \"\n ],\n [\n \" BRIEF SUMMARY OF THE INVENTION Provided herein is an exercise machine reversible resistance system which includes an exercise machine which has a movable exercise implement.\",\n \"The exercise implement is adapted to move with a drive belt which is connected at one end to a drive pulley and at the other end to an idler pulley.\",\n \"The exercise implement includes a clutch which selectively engages with different positions on the inner surface of the drive belt to adjust a direction of resistance applied against movement of the exercise implement.\",\n \"The clutch is movable between three positions: a first position in which the clutch is disengaged and no resistance is applied against the exercise implement, a second position in which the clutch is engaged with a first portion of the drive belt and resistance is applied against movement of the exercise implement in a first direction, and a third position in which the clutch is engaged with a second portion of the drive belt and resistance is applied against movement of the exercise implement in a second direction.\",\n \"There has thus been outlined, rather broadly, some of the features of the invention in order that the detailed description thereof may be better understood, and in order that the present contribution to the art may be better appreciated.\",\n \"There are additional features of the invention that will be described hereinafter and that will form the subject matter of the claims appended hereto.\",\n \"In this respect, before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not limited in its application to the details of construction or to the arrangements of the components set forth in the following description or illustrated in the drawings.\",\n \"The invention is capable of other embodiments and of being practiced and carried out in various ways.\",\n \"Also, it is to be understood that the phraseology and terminology employed herein are for the purpose of the description and should not be regarded as limiting.\"\n ],\n [\n \"CROSS REFERENCE TO RELATED APPLICATIONS The present application is a continuation of U.S. application Ser.\",\n \"No.\",\n \"14/840,910 filed on Aug. 31, 2015 (Docket No.\",\n \"LAGR-055), which claims priority to U.S.\",\n \"Provisional Application No.\",\n \"62/043,503 filed Aug. 29, 2014 (Docket No.\",\n \"LAGR-038).\",\n \"Each of the aforementioned patent applications, and any applications related thereto, is herein incorporated by reference in their entirety.\",\n \"STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT Not applicable to this application.\",\n \"BACKGROUND OF THE INVENTION Field of the Invention The present invention relates generally to an exercise machine and more specifically it relates to an exercise machine reversible resistance system for reversing the directional force of resistance against an exercise implement before, during, or after the performance of a routine of one or more exercises.\",\n \"Description of the Related Art Any discussion of the related art throughout the specification should in no way be considered as an admission that such related art is widely known or forms part of common general knowledge in the field.\",\n \"Exercise is human physical activity that enhances or maintains overall physical health of an exerciser.\",\n \"Exercise is performed to increase muscle strength, improve balance, improve cardiovascular efficiency, and to aid in weight loss.\",\n \"Cardiovascular exercises are intended to improve circulatory and respiratory performance and health by raising the heart rate for an extended period of time, increasing oxygenation and calorie burn.\",\n \"Within the fitness industry, cardiovascular exercise as often referred to as “cardio”.\",\n \"Typical cardio exercise equipment found in gyms includes treadmills, stationary bikes, elliptical trainers, and stair climbers.\",\n \"Cardio exercises performed without the aid of specialized apparatuses include running and swimming.\",\n \"Strength exercises are intended to increase the ability for muscles to perform more work.\",\n \"The exercises are practiced consistently over weeks or months.\",\n \"Strength exercises are typically performed in short but high intensity muscle bursts, rather than the long duration of cardio exercises.\",\n \"Strength training is intended to break down the muscles targeted by the exercise.\",\n \"The subsequent repair of muscle tissue after training is achieved by increased localized blood circulation that delivers nutrients and oxygen, both of which promote repair and growth of the muscle beyond its size and strength prior to exercise.\",\n \"Strength exercise machines are apparatuses or devices providing for fixed or adjustable amounts of resistance, and which are used during physical activity to enhance the strength or conditioning effects of the performed exercises.\",\n \"Myriad apparatuses have been made available by many manufacturers, each apparatus intended to work one targeted muscle or group of muscles.\",\n \"For instance, a bicep curl machine is intended to exercise only the bicep muscles, while a chest press machine is intended to primarily exercise the chest muscles, but to a lesser degree, shoulder and triceps muscles.\",\n \"Strength exercise apparatuses may incorporate as the resistance source free weights, for example, barbells, dumbbells or stacked weights, resistance springs or bands, or position the exerciser so as to use the exerciser's own body weight as the weight resistance source.\",\n \"Contemporary methods of exercising against a workload are many, and well known to those skilled in the art.\",\n \"One method of creating a direct vertical workload is an exerciser's application of force to lift a dead weight from a resting position to a higher vertical position.\",\n \"Another method of creating a horizontal workload is to redirect a vertical workload along a horizontal vector using a pulley or mechanical linkage.\",\n \"Yet another method of creating a workload in any direction is to apply a force opposite the force axis of a variable resistance means, such as a spring or elastic resistance band.\",\n \"Still another method of creating a workload is to require a continuous cycle of lifting one's own body weight.\",\n \"For instance, a person exercising on a motorized treadmill is required to increase or decrease the elevation through which they lift their body with each step, and/or to increase or decrease the speed or length of stride in order to maintain their relatively stationary position upon the moving treadmill belt.\",\n \"Increasing the pitch of the treadmill belt further causes the exerciser to increase their work by lifting their body weight higher with each step in order to maintain their position on a treadmill.\",\n \"Those skilled in the art will recognize that most all exercise apparatuses provide for continuous or cyclical exercising in one primary direction.\",\n \"For instance, an bicep curl machine is operated by an exerciser repeatedly flexing their bicep to raise their lower arm against a prescribed weight, then by slowly releasing the bicep muscle flex, allows the re-extension of their lower arm to return the weight to the starting point, then repeat the cycle for a prescribed number of times.\",\n \"On the other hand, a triceps apparatus works opposite to a bicep curl apparatus in that the primary work is performed by flexing the triceps to extend the forearm to substantially align with the upper arm while working against a weight or resistance.\",\n \"By slowly relaxing the triceps, the weight is returned to its starting point as the lower arm assumes a decreasing angle relative to the upper arm.\",\n \"As can readily be understood in the foregoing descriptions, exercise machines are intended to deliver a workload in one direction only.\",\n \"The primary work cycle on a bicep machine is achieved when the hand working against the resistance approaches the shoulder, while the primary work cycle on a triceps machine is achieved when the hand working against the resistance moves away from the shoulder.\",\n \"Therefore, a bicep machine does not appreciably exercise triceps, and a triceps machine does not appreciably exercise the biceps.\",\n \"Another form of exercise produces a mixed benefit of combining cardio and strength training.\",\n \"Known to those skilled in the art, circuit training is a form of exercise that requires the exerciser to continuously work against resistance for a prolonged period, as previously described in cardio exercises, yet also incorporates a routine of large number of exercises that are performed in a rapid sequence, without any appreciable rest between each exercise.\",\n \"One variation of circuit training is sometimes referred to as interval training wherein the exerciser generally performs the same exercise for a period of specific duration, similar to cardio exercising, but varies the resistance level throughout the routine period to substantially increase the exerciser's workload for short duration, high intensity bursts, then decrease the workload during a moderate recovery period whereby the cardio exercise intensity is maintained until a subsequent burst.\",\n \"The exerciser repeats this high/low intensity cycle until the end of the training period.\",\n \"A disadvantage of attempting to perform circuit or interval training on a variety of exercise apparatuses by immediately and without an appreciable rest period, moving from one apparatus for one exercise, to another apparatus for a subsequent exercise is that in a typical gym environment, there will be another exerciser already working out on the next apparatus in the sequence, forcing the circuit exerciser to wait until the apparatus is available.\",\n \"This breaks the intended benefits of the continuous cycle of circuit training.\",\n \"Another disadvantage of performing circuit training using multiple apparatuses in sequence within a gym environment is that even if the next apparatus is vacant, the proper weight, resistance level, or direction of resistance must be re-set for each exerciser.\",\n \"In many instances, this is time consuming, confusing, and the proper weight setting cannot be readily determined.\",\n \"Again, the break in the circuit sequence reduces the intended advantages of the circuit training session.\",\n \"A disadvantage of attempting to perform a variation of circuit training upon a single exercise apparatus is that an exerciser must stop the exercise routine, most often by having to dismount the apparatus in order to change the existing resistance settings to new settings or to reverse the direction of resistance.\",\n \"The exerciser then re-mounts the apparatus and re-establishes proper positioning before continuing a new exercise at the new resistance setting.\",\n \"However, after a short period of performing a first exercise, often merely a minute or two, the exerciser would have to again dismount and change the resistance settings or the direction of resistance for a second exercise—then repeat the entire process with many additional exercises included in the particular routine.\",\n \"It often takes more time to change the resistance settings than the period of time the exerciser will actually perform the new exercise at the new setting.\",\n \"Still another disadvantage of all of the exercise machines and Pilates apparatuses just described is that the resistance is unidirectional.\",\n \"In other words, none of the machines provide for an exerciser to immediately change the direction of the resistance force.\",\n \"As an example, the rotating belt of a motorized treadmill is intended to move such that an exerciser, facing the front of the machine, can walk or run at different speeds, on a flat, or “uphill”.\",\n \"Reversing the rotation of the rotating belt would require the exerciser to begin walking or running backwards, and possibly “downhill”.\",\n \"Not only would this be an unnatural exercise, reversing a treadmill belt during exercise would be dangerous, and would likely be the source of many injuries.\",\n \"As another example, a pull down machine to exercise the latissimus dorsi muscles provides a seat upon which an exerciser sits, and an overhead bar attached to a cable.\",\n \"The cable is threaded through a pulley on the machine, and is attached to weights.\",\n \"When an exerciser pulls down the overhead bar to work the latissimus dorsi or back muscles, the downward direction of their pull is reversed through the pulley, and they are actually pulling the weights that are attached to the cable upward from the floor.\",\n \"On the other hand, there is no provision to allow the exerciser to switch resistance direction so they can push upward on the bar and lift the weights to exercise the shoulders as would be provided by a shoulder press machine.\",\n \"Pushing upward provides no work resistance.\",\n \"Yet another exemplary embodiment of the present invention is an improved exercise apparatus with a force reversing system providing for a plurality of exercise resistance springs affixed to an apparatus structure, a means providing for an exerciser to input an exercising force in one moveable direction sufficient to overcome one or more of the resistance springs, and a system providing for an exerciser to immediately reverse the direction of motion against which a counteracting resistance force will be applied.\",\n \"For instance, an exerciser's upward force movement as required to work against the spring resistance can be reversed to a downward force required to work against the spring resistance.\",\n \"Another object of the present invention is an improved Pilates apparatus comprising a substantially longitudinal frame, an idler pulley affixed at substantially one end of the apparatus, a driven pulley on a drive shaft affixed at substantially the opposed end of the apparatus, a drive belt affixed to at least the idler and driven pulleys, and therebetween, an exercise carriage slidable along the longitudinal axis of the apparatus, the carriage being optionally engageable along the length of either side of the drive belt, thereby allowing an exerciser to select which direction the slidable carriage and correspondingly, the rotational direction of the driven pulley will move responsive to an exercise force input exerted upon the slidable platform.\",\n \"The reverser as currently illustrated is ‘self energizing’.\",\n \"This means that the more force an exerciser applies to the platform, pull the harder it tries to engage.\",\n \"A beneficial side effect is that if the exerciser pushes the rollable platform in the wrong direction, it disengages, thus preventing the platform back driving the spring mechanism.\",\n \"Those skilled in the art will immediately recognize the deficiencies just described, and will understand that a sufficiently large number of machines to allow exercising of each major muscle group housing many machines requires leasing a large and expansive area for a functional gym or Pilates studio.\",\n \"They will appreciate that one machine capable of providing resistance for a wide variety of exercises allows for more economically efficient operations.\",\n \"Further, fitness experts and gym operations will appreciate the commercial advantages of a new and improved exercise apparatus that provides for immediate and precise changing of the resistance level without considerable interruption to a workout routine, and a system of immediately reversing the direction of resistance to increase the number of muscles and muscle groups that may be exercised without dismounting the apparatus, thereby obviating the need to make complicated changeovers to the apparatus, or to move to another machine to perform a different exercise.\",\n \"Because of the inherent problems with the related art, there is a need for a new and improved exercise machine reversible resistance system for reversing the directional force of resistance against an exercise implement before, during, or after the performance of a routine of one or more exercises.\",\n \"BRIEF SUMMARY OF THE INVENTION Provided herein is an exercise machine reversible resistance system which includes an exercise machine which has a movable exercise implement.\",\n \"The exercise implement is adapted to move with a drive belt which is connected at one end to a drive pulley and at the other end to an idler pulley.\",\n \"The exercise implement includes a clutch which selectively engages with different positions on the inner surface of the drive belt to adjust a direction of resistance applied against movement of the exercise implement.\",\n \"The clutch is movable between three positions: a first position in which the clutch is disengaged and no resistance is applied against the exercise implement, a second position in which the clutch is engaged with a first portion of the drive belt and resistance is applied against movement of the exercise implement in a first direction, and a third position in which the clutch is engaged with a second portion of the drive belt and resistance is applied against movement of the exercise implement in a second direction.\",\n \"There has thus been outlined, rather broadly, some of the features of the invention in order that the detailed description thereof may be better understood, and in order that the present contribution to the art may be better appreciated.\",\n \"There are additional features of the invention that will be described hereinafter and that will form the subject matter of the claims appended hereto.\",\n \"In this respect, before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not limited in its application to the details of construction or to the arrangements of the components set forth in the following description or illustrated in the drawings.\",\n \"The invention is capable of other embodiments and of being practiced and carried out in various ways.\",\n \"Also, it is to be understood that the phraseology and terminology employed herein are for the purpose of the description and should not be regarded as limiting.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS Various other objects, features and attendant advantages of the present invention will become fully appreciated as the same becomes better understood when considered in conjunction with the accompanying drawings, in which like reference characters designate the same or similar parts throughout the several views, and wherein: FIG.\",\n \"1 is an upper perspective view of an exemplary embodiment of the present invention.\",\n \"FIG.\",\n \"2 is a side sectional view of a horizontal embodiment of the present invention in a first configuration.\",\n \"FIG.\",\n \"3 is a side sectional view of a horizontal embodiment of the present invention in a second configuration.\",\n \"FIG.\",\n \"4 is a side sectional view of a vertical embodiment of the present invention in a first configuration.\",\n \"FIG.\",\n \"5 is a side sectional view of a vertical embodiment of the present invention in a second configuration.\",\n \"FIG.\",\n \"6 is an upper perspective view of an additional exemplary embodiment of the present invention in which the elongated member is a chain.\",\n \"DETAILED DESCRIPTION OF THE INVENTION Various aspects of specific embodiments are disclosed in the following description and related drawings.\",\n \"Alternate embodiments may be devised without departing from the spirit or the scope of the present disclosure.\",\n \"Additionally, well-known elements of exemplary embodiments will not be described in detail or will be omitted so as not to obscure relevant details.\",\n \"Further, to facilitate an understanding of the description, a discussion of several terms used herein follows.\",\n \"The word “exemplary” is used herein to mean “serving as an example, instance, or illustration.” Any embodiment described herein as “exemplary” is not necessarily to be construed as preferred or advantageous over other embodiments.\",\n \"Likewise, the term “embodiments” is not exhaustive and does not require that all embodiments include the discussed feature, advantage or mode of operation.\",\n \"Turning now descriptively to the drawings, in which similar reference characters denote similar elements throughout the several views, FIGS.\",\n \"1 through 5 illustrate an exercise machine reversible resistance system 10, which comprises a frame 23 having a first end and a second end, an elongated member 31 movably positioned upon the frame 23, a resistance device 52 connected to the elongated member 31, an exercise implement 26 movably connected to the frame 23, and a clutch 60 connected to the exercise implement 26.The elongated member 31 has a first run 31a and a second run 31b between the first end and the second end of the frame as illustrated in FIGS.\",\n \"1 through 5.When the first run 31a moves in a first direction the second run 31b moves in a second direction that is substantially opposite of the first direction and when the first run 31a moves in the second direction the second run 31b moves in the first direction.\",\n \"The resistance device 52 applies a resistance force to the elongated member 31 in the second direction relative to the first run 31a and applies the resistance force to the elongated member 31 in the first direction relative to the second run 31b.\",\n \"The clutch 60 is adapted to selectively engage the first run 31a or the second run 31b of the elongated member 31.The exercise implement 26 receives the resistance force in the second direction when the clutch 60 is engaged to the first run 31a as shown in FIGS.\",\n \"1, 2 and 4 of the drawings.\",\n \"The exercise implement 26 receives the resistance force in the first direction when the clutch 60 is engaged to the second run 31b as shown in FIGS.\",\n \"3 and 5 of the drawings.\",\n \"The clutch 60 is preferably comprised of a linear clutch to move in a linear manner.\",\n \"The first run 31a and the second run 31b are preferably substantially parallel with respect to one another as illustrated in FIGS.\",\n \"1 through 5.The first run 31a and the second run 31b may be horizontally aligned (FIGS.\",\n \"1 through 3), vertically aligned (FIGS.\",\n \"4, 5) or aligned at an angle between horizontal and vertical.\",\n \"The first run 31a may be positioned above, below, to the left or to the right of the second run 31b.\",\n \"The first run 31a is distally spaced apart from the second run 31b.\",\n \"The elongated member 31 is comprised of an endless loop structure that rotates around a first wheel 30 and a second wheel 35.The first wheel 30 is rotatably connected to the frame 23 and the second wheel 35 is rotatably connected to the frame 23 distally spaced from the first wheel 30 as illustrated in FIGS.\",\n \"1 through 5 of the drawings.\",\n \"The elongated member 31 is movably positioned upon the first wheel 30 and the second wheel 35, wherein the first run 31a and the second run 31b are positioned between the first wheel 30 and the second wheel 35.The elongated member 31 preferably includes a plurality of teeth 32 that are selectively engageable by the clutch 60.The plurality of teeth 32 preferably extend inwardly toward one another between the two opposing runs 31a, 31b as illustrated in FIGS.\",\n \"1 through 5 of the drawings.\",\n \"The elongated member 31 may be comprised of a belt, chain or other elongated structure.\",\n \"The elongated member 31 is preferably comprised of a non-stretchable material.\",\n \"The resistance device 52 may be directly connected to the elongated member 31 or indirectly connected to the elongated member 31.For example, the resistance device 52 may be connected to the first wheel 30 to apply the resistance force against rotation of the first wheel 30 in a first rotational direction.\",\n \"The resistance device 52 may be comprised of a bias member that is elongated and resilient (e.g.\",\n \"elastic member, spring).\",\n \"The clutch 60 is comprised of an actuator 70 and an engagement portion 64 extending from the actuator 70.The actuator 70 may be comprised of a manually operated actuator (e.g.\",\n \"a lever) or a powered actuator (e.g.\",\n \"electric motorized actuator).\",\n \"The engagement portion 64 has a retracted position for engaging the first run 31a as shown in FIGS.\",\n \"1, 2, 4 of the drawings.\",\n \"The engagement portion 64 of the clutch 60 also preferably has an extended position for engaging the second run 31b as shown in FIGS.\",\n \"3, 5 of the drawings.\",\n \"The invention in one embodiment is comprised of a frame 23 to which are connected a first wheel 30 and a second wheel 35.The first wheel 30 and second wheel 35 will generally be spaced-apart, though the distance by which they are separated will vary in different embodiments of the present invention.\",\n \"In the embodiment shown in the figures, the first wheel 30 is positioned at or near the first end 21 of the exercise machine 20 and the second wheel 35 is positioned at or near the second end 22 of the exercise machine 20.An elongated member 31 is shown as connecting the first wheel 30 with the second wheel 35 such that rotation of the first wheel 30 will similarly rotate the freely-rotatable second wheel 35.The first wheel 30 includes a first run 31a and a second run 31b.\",\n \"It is noted that the particular locations along the inner surface of the elongated member 31 which comprise the first run 31a and second run 31b will vary as the elongated member 31 traverses the path between the first wheel 30 and second wheel 35.Thus, the same location on the inner surface of the elongated member 31 which comprises a first run 31a will comprise the second run 31b of the elongated member 31 at a different time depending on positioning of the elongated member 31 on the first wheel 30 and second wheel 35 at that particular time.\",\n \"The elongated member 31 of the present invention may comprise various configurations, and should not be construed as limited by the exemplary figures.\",\n \"In a preferred embodiment as shown in the figures, the elongated member 31 comprises a belt having a plurality of teeth 32 extending along its inner surface.\",\n \"In other embodiments, the elongated member 31 could comprise a chain with a plurality of links, rather than teeth 32.In other embodiments, the elongated member 31 could comprise a flat surface without any projections such as teeth 32 as discussed herein.\",\n \"The exercise machine 20 includes an exercise implement 26 which is freely-movable in at least two directions, such as by being movably connected to a frame 23 or rails 27.The exercise machine 20 may be free-standing, such as through use of support feet 24, or may be connected to another structure, such as in a cantilevered configuration.\",\n \"A bias member 52 is interconnected with the exercise implement 26 as discussed herein such that the bias member 52 will exert resistance against movement of the exercise implement 26 in multiple directions depending on positioning of a clutch 60.The exercise implement 26 may comprise various structures, devices, and the like, and should not be construed as limited by the exemplary figures herein.\",\n \"FIGS.\",\n \"1-3 illustrate an embodiment in which the exercise implement 26 comprises a movable carriage.\",\n \"FIGS.\",\n \"4-5 illustrate an embodiment in which the exercise implement 26 comprises a handle 25.Various other types of exercise implements 26 may be utilized.\",\n \"The clutch 60 of the present invention extends from the exercise implement 26; with the clutch 60 being movably connected to the exercise implement 26 in some embodiments.\",\n \"The clutch 60 is adapted to selectively engage with the first run 31a of the elongated member 31 to apply resistance against movement of the exercise implement 26 in a first direction and to selectively engage with the second run 31b of the elongated member 31 to apply resistance against movement of the exercise implement 26 in a second direction.\",\n \"Thus, use of the clutch 60 is operable to change the direction of resistance being applied against movement or manipulation of the exercise implement 26.The clutch 60 may comprise various configurations and should not be construed as limited by the exemplary figures.\",\n \"In the exemplary embodiment shown in the figures, the clutch 60 comprises an extension portion 62 which is connected at a first end to the exercise implement 26 and at a second end to an engagement portion 64.The extension portion 62 may extend vertically downward as shown in the figures, or may extend in different orientations.\",\n \"The engagement portion 64 is illustrated as extending diagonally with respect to the downwardly-extending extension portion 62, with the first end 65 of the engagement portion 64 being adapted to engage with the first run 31a of the elongated member 31 and the second end 66 of the engagement portion 64 being adapted to engage with the second run 31b of the elongated member 31.The manner in which resistance from the bias member 52 is transferred to be applied against movement of the exercise implement 26 will vary in different embodiments.\",\n \"One such embodiment is illustrated in the figures; however, the present invention should not be construed as being limited in any respect by the exemplary embodiment.\",\n \"There are numerous manners in which the resistance force of the bias member 52 may be transferred to be applied against the exercise implement 26.As shown in FIGS.\",\n \"1-5, one such embodiment comprises the use of gear reduction pulleys 40, 42.In this exemplary embodiment, a first gear reduction pulley 40 shares the same drive shaft 33 as the first wheel 30 such that the first gear reduction pulley 40 and the drive shaft 33 are concentric.\",\n \"The first gear reduction pulley 40 will generally comprise a smaller diameter than the first wheel 30 as shown in the figures.\",\n \"A second gear reduction pulley 42 is connected to the exercise machine 20, such as its frame 23, by a gear reduction shaft 44.The first gear reduction pulley 40 is connected to the second gear reduction pulley 42 by a gear reduction belt 43 such that the first and second gear reduction pulleys 40, 42 rotate together.\",\n \"In the embodiment shown in the figures, the second gear reduction pulley 42 is larger in diameter than the first gear reduction pulley 40.A separate resistance pulley 56 is illustrated as sharing the same gear reduction shaft 44 as the second gear reduction pulley 42, with the resistance pulley 56 being concentric with the second gear reduction pulley 42.The resistance pulley 56 may comprise a smaller diameter than the first wheel 30 as shown in the figures.\",\n \"The resistance pulley 56 and second gear reduction pulley 42 may comprise substantially the same diameter as shown in the figures, or may comprise different diameters.\",\n \"The resistance pulley 56 is interconnected with the bias member 52 of the present invention.\",\n \"In some embodiments, the bias member 52 may be directly connected to the resistance pulley 56.In other embodiments, a separate bias connector 50 may be provided which connects between the bias member 52 and the resistance pulley 56.As shown in the figures, one embodiment of the bias connector 50 is comprised of a cable, with the cable being connected at one end to the resistance pulley 56 and at the other end to the bias member 52.The bias member 52 may comprise various structures known to exert resistance, such as a spring as shown in the figures.\",\n \"To maintain tension on the drive belt 30, a tensioner pulley 38 may be provided which exerts force against the drive belt 30 to maintain its tension as shown in the figures.\",\n \"The tensioner pulley 38 may be located anywhere along the length of the drive belt 30, including embodiments which exert tension against the upper portion of the drive belt 30 and embodiments (such as shown in the figures) which exert tension against the lower portion of the drive belt 30.The tensioner pulley 38 will preferably be mounted on its own tensioner shaft 39; with the tensioner shaft 39 being connected to the exercise machine 20, such as to its frame 23.The exercise machine reversible resistance system 10 is adapted to transition between a push-force configuration shown in FIGS.\",\n \"2 and 4, in which the exercise implement 26 is resisted as it is moved in a first direction FE1, and a pull-force configuration shown in FIGS.\",\n \"3 and 5, in which the exercise implement 26 is resisted as it is moved in a second direction FE2.As illustrated throughout the figures, the first direction FE1 is opposite with respect to the second direction FE2.FIG.\",\n \"1 is an exemplary upper perspective view of the present invention.\",\n \"While this figure illustrates the exercise machine 20 as comprising a Pilates machine configuration, various types of other exercise machines 20 may be utilized as discussed herein.\",\n \"An exercise implement 26 is provided as part of the exercise machine 20, and may be connected to any portion of the exercise machine 20.The positioning of the exercise implement 26 will vary depending on the type of exercise machine 20 being utilized.\",\n \"Any type of exercise machine 20 which utilizes an exercise implement 26 and bias members 52, such as rowing machines, weight lifting machines, universal exercise machines, press machines, squat machines, curl machines, triceps machines, dip machines, elliptical trainers, and the like.\",\n \"Thus, the present invention should not be construed as being limited to any particular type of exercise machine 20 or exercise implement 26.By way of example, FIGS.\",\n \"1-3 illustrate the present invention being utilized in combination with a Pilates machine.\",\n \"As an additional example, FIGS.\",\n \"4-5 illustrate the present invention being utilized in combination with an exercise machine 20 adapted to function as either a curl machine or a triceps machine depending on its configuration.\",\n \"FIG.\",\n \"2 is an exemplary diagram showing a side view of an exercise machine reversible resistance system 10 which is in a push-force configuration.\",\n \"More specifically, in the push-force exercise configuration as shown in FIG.\",\n \"1, an elongated member 31 is installed around a first wheel 30 and a second wheel 35.The first wheel 30 is affixed to a rotatable drive shaft 33 and the second wheel 35 is affixed to a rotatable idler shaft 36, with the drive shaft 33 and idler shaft 36 being secured to the exercise machine 20, such as to its frame 23.A tensioner pulley 38 is provided as a means to create a preferred tension on the elongated member 31, with the tensioner pulley 38 being affixed to a rotatable tensioner shaft 39.As shown in FIG.\",\n \"2, a clutch 60 in the “push” position affixed to the exercise implement 26 is selectively engageable with the elongated member 31 such that when an exerciser 12 applies an exercise force FE1 in the direction shown, the exercise implement 26 moves along the length of the exercise machine 20, and the elongated member 31 correspondingly moves in the same direction, for the same length of travel as the exercise implement 26.A first gear reduction pulley 40 is affixed to the same drive shaft 33 as the first wheel 30, with the first gear reduction pulley 40 and the first wheel 30 being concentric.\",\n \"The first gear reduction pulley 40 is adapted such that the first gear reduction pulley 40 rotates in response to exercise forces exerted upon the elongated member 31.Rotation of the first gear reduction pulley 40 rotates a second gear reduction pulley 42 which is separately connected to a gear reduction shaft 44; with the first gear reduction pulley 40 and the second gear reduction pulley 42 being interconnected by a gear reduction drive belt 43, thereby reducing the angle of rotation of the a resistance pulley 56 connected to the same gear reduction shaft 44 relative to the first gear reduction pulley 40.As shown in the figures, the resistance pulley 56 is connected to the gear reduction shaft 44 such that the resistance pulley 56 and the second gear reduction pulley 42 are concentric.\",\n \"The resistance pulley 56 is preferably of a smaller diameter than the first wheel 30 and a larger diameter than the first gear reduction pulley 40 as shown in the figures.\",\n \"The bias member 52 is interconnected with the resistance pulley 56 such that resistance force is applied against rotation of the resistance pulley 56 in a first direction.\",\n \"The bias member 52 may be directly connected to the resistance pulley 56, or may be connected to the resistance pulley 56 by a bias connector 50 such as a cable as shown in the figures.\",\n \"It is preferable that the first end 53 of the bias members 52, where affixed to a bias connector 50, travel a distance shorter than the measurable travel of the exercise implement 26.The second end 54 of the bias members 52 is attached to the frame 23.More specifically, the use of the gear reduction pulleys 40, 42 just described limits the rotation of the resistance pulley 56 to one revolution relative to the total range of travel of the exercise implement 26, thereby limiting the bias connector 50 or bias member 52 winding about the resistance pulley 56 to one wrap.\",\n \"It is well known to those skilled in the art that when a cable is wrapped multiple times around itself on a pulley, the effective diameter of the pulley increases, and the force necessary to rotate the pulley increases.\",\n \"In the exercise machine of the present invention, a constant and predictable linear force against a predetermined resistance force FR is preferred to the requirement of an increasing force to continue rotating the resistance pulley 56.As the second gear reduction pulley 42 is rotated in response to the input exercise force upon the exercise implement 26, the resistance pulley 56 similarly rotates with the same gear reduction shaft 44 such that the bias connector 50 free length shortens, thereby overcoming a predetermined resistance force FR extending one or more of the bias members 52 provided as a means to resist the exercise input force FE1.Oftentimes, it is preferable that an exerciser 12 contracts muscles that pull loads or resistance, rather than contracting opposing muscles that push loads or resistances.\",\n \"In such situations, an exerciser would shift the clutch from a “push” position as shown in FIGS.\",\n \"2 and 4 to a “pull” position shown in FIGS.\",\n \"3 and 5, thereby engaging teeth 32 on the elongated member 31 on the opposite side of the first wheel 30.As can readily be seen in the pull-force exercise configuration shown in the figures, with the clutch 60 engaged in the pull position and disengaged in the push position, the exerciser 12 may immediately begin exerting an exercise force on the exercise implement 26 in the opposite direction FE2, thereby providing for the engagement and exercise of the pulling muscles by directing the force against a resistance force FR.\",\n \"Those expert in exercise machines 20, and more specifically Pilates apparatuses, will immediately appreciate the benefit of providing the previously unknown system and method of reversing the direction of force that an exercise exerts upon an exercise implement 26, including the ability to change from a pulling exercise to pushing exercise with little or no interruption of the overall exercise routine, and the elimination of the traditional requirement for an exerciser 12 to completely rotate their position upon an exercise machine 20 so that they are facing in a second direction opposite of the first direction so that they can engage a different set of muscles.\",\n \"Further, they will appreciate that by providing for the reversal of force direction upon the exercise implement 26, the pushing and pulling exercises may be applied to a set of handles 25 at a first end 21 of the exercise machine 20, thereby eliminating the requirement for any handles 25 at the second end 22 of the exercise machine 20.The figures illustrate the elongated member 31 as comprising a belt having a plurality of teeth 32 on its inner circumference.\",\n \"One of ordinary skill in the art will appreciate that multiple other types of drive connectors 31 may be utilized with the present invention, such as chains and the like.\",\n \"It should be noted that the preferable use of teeth 32 on the elongated member 31 is not meant to be limiting, flat belts, V-belts, as well as chains delivering the functionality just described may be used without deviating from the novel functionality of the present invention.\",\n \"Further, the preferred clutch 60 system just described provides for the engagement of gear features of the clutch 60, such as either of the ends 65, 66 of the engaging portion 64 shown in the figures, with teeth 32 on the elongated member 31 is not meant to be limiting, and the alternative methods of engaging a clutch 60 with an elongated member 31 such as a belt may include friction clamps such as a V-grooved plate engageable with a V-belt.\",\n \"Therefore, many methods of engaging the inside surface of a drive connector are well known, and may be used to accomplish the intended result in the novel, and previously unavailable system and method of the present invention providing for reversibly directing an exerciser's exercise force against one or more springs that provide resistance force FR in only one direction FE1 or FE2.In use, the clutch 60 will generally start in a position in which it is not engaged with any portion of the elongated member 31.In this position, the exercise implement 26 may freely traverse the exercise machine 20 without any resistance from the bias member 52.The exerciser 12 may freely position the exercise implement 26 at the desired location to begin an exercise without any force of resistance being transferred from the bias member 52 while the clutch 60 is disengaged.\",\n \"Once the exercise implement 26 is located at the desired starting position for exercises, the clutch 60 may be engaged such that the bias member 52 exerts resistance against the exercise implement 26 as it is moved in a first direction FE1.In this case, the clutch 60 may be pulled upwardly such that the first end 65 of the engagement portion 64 of the clutch 60 engages with the first run 31a of the elongated member 31 as shown in FIG.\",\n \"2.One manner of such engagement is shown in the figures, in which the first end 65 of the engagement portion 64 engages with the teeth 32 on the first run 31a of the first wheel 30.The exerciser 12 may then perform various exercises with the exercise implement 26 being biased against movement in the first direction FE1.Upon completion a first set of exercises, the exerciser 12 may desire to reverse the direction of resistance.\",\n \"Utilizing the present invention, the exerciser 12 may easily and efficiently reverse the direction of resistance against the exercise implement 26 using only the clutch.\",\n \"Without getting off the carriage 12 or manipulating any other structure, the exerciser 12 may simply force the clutch 60 downwardly such that the first end 65 of the engagement portion 64 disengages with the first run 31a of the elongated member 31.With continued downward force, the second end 66 of the engagement portion 64 will engage with the second run 31b of the elongated member 31.When so configured, the exercise implement 26 will be resisted against movement in the second direction FE2.The exerciser 12 may then continue with a different set of exercises which utilizes the opposite direction of resistance than the first set of exercises.\",\n \"The exerciser 12 may repeat these steps repeatedly to perform different sets of exercises against different directions of resistance.\",\n \"The exerciser 12 may dismount the present invention at any time.\",\n \"It may be preferable to position the clutch 60 in its disengaged position (i.e.\",\n \"the engagement portion 64 does not engage with any portion of the elongated member 31) such that the exercise implement 26 is freely movable into any position by a future exerciser 12.FIGS.\",\n \"4 and 5 are exemplary diagrams showing a side view of the present invention in a vertical orientation.\",\n \"More specifically, the embodiment of the exercise machine reversible resistance system 10 shown in FIGS.\",\n \"1-3 is shown rotated so that the longitudinal axis to which a linear exercise force is applied to an exercise implement 26 is tilted so that the exercise force axis is substantially vertical.\",\n \"Utilizing the same principles as previously described, the present invention provides for a plurality of exercises typically performed while the upper body is substantially vertical.\",\n \"For instance, those skilled in the art will appreciate that exercise machines 20 referred to as bicep curl machines allow an exerciser 12 to approach the machine, with arms substantially straight and extended grasp a handle 25 serving as an exercise implement 26 with one or both hands, and contract the bicep muscle against a resistance force until the hand is proximal to its respective shoulder.\",\n \"Thereafter, the exerciser would reverse the action, slowly releasing the bicep contraction, thereby allowing the lower arm to extend back to substantially the starting position.\",\n \"One advantage of the present invention is that the exercise machine 20 as previously described weighs less than a machine that uses stacked weights.\",\n \"For example, a plurality of bias members 52, together with an indexable resistance level selector with 15 ten pound increments, would provide a maximum of 150 lbs or resistance force for exercising biceps.\",\n \"The gross weight of the apparatus that includes the transmission system and bias members 52 would be estimated to weigh 80 pounds, depending on materials construction.\",\n \"On the other hand, traditional curl machines using similar materials as just described, and that provide 150 pounds maximum resistance force, would necessarily contain a stack of 15 ten pound iron or steel weights, thereby weighing at least 150 pounds.\",\n \"Therefore, the weight savings which correspond to reduced manufacturing and freight costs, and reduced labor costs for delivering and setting up a curl machine in a gym are all reduced; making the variable transmission system commercially advantageous.\",\n \"Further, by integrating the reversing clutch 60 system as herein described, the curl machine embodiment of the present invention shown in FIGS.\",\n \"4-5 can be immediately reversed, thereby becoming a triceps machine wherein an exerciser 12 starts with bent arms, and after grasping the handle 25 which serve as exercise implements 26, may then extend their arms while pushing the handles 25 with a downward force by flexing their triceps.\",\n \"It is well known that exercisers 12 are advised to exercise counteracting muscles during a workout.\",\n \"Therefore, triceps and biceps are counteracting muscles, and after completing exercises for one muscle group, the opposing muscle group should be exercised.\",\n \"Traditional gym machines do not provide for the reversing of the direction of exercise force since they are single exercise/single purpose designed.\",\n \"The novel function of the present invention provides for one exercise machine 20 that may functionally replace at least two traditional exercise apparatuses.\",\n \"Therefore, the present invention is more commercially valuable when compared to traditional gym machines in that it provides for significant reduction in the acquisition of equipment needed for a full service gym, and since in many instances, one exercise machine 20 of the present invention can replace the functionality of two machines, allowing a gym to provide the same exercise capacity, but with a substantially reduced facility size.\",\n \"Although specific embodiments have been illustrated and described herein, it will be appreciated by those of ordinary skill in the art that a wide variety of alternate and/or equivalent implementations may be substituted for the specific embodiments shown and described without departing from the scope of the present disclosure.\",\n \"This application is intended to cover any adaptations or variations of the embodiments discussed herein.\",\n \"Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.\",\n \"Although methods and materials similar to or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described above.\",\n \"All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety to the extent allowed by applicable law and regulations.\",\n \"The present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof, and it is therefore desired that the present embodiment be considered in all respects as illustrative and not restrictive.\",\n \"Any headings utilized within the description are for convenience only and have no legal or limiting effect.\"\n ]\n]"},"source":{"kind":"string","value":"Patent_15871950"}}},{"rowIdx":4493963,"cells":{"text":{"kind":"list like","value":[["METHODS AND APPARATUS FOR TREATMENT OF CHRONIC KIDNEY DISEASE","A method and apparatus for treatment of chronic kidney disease (CKD), particular diabetic nephropathy, are disclosed.","The method comprises activation of adenosine A2a receptors in parenchymal and immune cells infiltrated into kidneys.","The activation is performed by PEMF (pulsed electromagnetic field) stimulation applied locally to kidneys.","Adenosine A2a signaling pathway is a potent anti-inflammatory and immuno-suppressive regulator that has been proven to attenuate inflammation and injury in diabetic nephropathy.","Efficient activation of A2a receptors is achieved by applying electromagnetic field stimulation consecutively in 3 spatial dimensions.","This allows attaining a significant increase in activation of A2a receptors in comparison with one-dimensional stimulation.","Assistant thermal stimulation may be applied to increase expression of heat shock proteins (HSPs) in parenchymal cells.","HSPs improve protein functions, protect cells from apoptosis and necrosis, increase metabolism, and symbiotically enhance effects of electric stimulation on CKD."],["1.A method of treating chronic kidney disease of a mammal, the method comprising: increasing a concentration of Ata adenosine receptors on cellular membranes in a kidney of the mammal by: delivering a first pulsed magnetic field with a first polarity to a kidney of the mammal along a first orthogonal direction; delivering a second pulsed magnetic field with the first polarity to the kidney of the mammal along a second orthogonal, the second orthogonal direction being perpendicular to the first orthogonal direction, the first and second orthogonal directions being in a common plane; and delivering a third pulsed magnetic field with the first polarity to the kidney of the mammal along a third orthogonal direction, the third orthogonal direction being perpendicular to the common plane.","2.The method of claim 1, further comprising delivering each of the first pulsed magnetic field, the second pulsed magnetic field and the third pulsed magnetic field to the kidney of the mammal in a second polarity that is the opposite of the first polarity.","3.The method of claim 1, further comprising: applying a pulsed electromagnetic field (PEMF) treatment session to the kidney of the mammal on at least three days during a seven day period, wherein each PEMF treatment session includes the steps of delivering the first pulsed magnetic field, the second pulsed magnetic field and the third pulsed magnetic field to the kidney of the mammal for a duration of two to four hours; and applying an independent whole body heat stimulation to the mammal two to four times during the seven day period to induce heat shock proteins in the kidney of the mammal.","4.The method of claim 1, further comprising heating the kidney of the mammal by energizing a high frequency generator.","5.The method of claim 1, further comprising generating a first electrical current in a first coil such that the first electrical current flows in a clockwise rotational direction in a first petal of the first coil and the first electrical current flows in a counter-clockwise rotational direction in a second petal of the first coil.","6.The method of claim 5, further comprising generating a second electrical current in a second coil such that the second electrical current flows in a clockwise rotational direction in a first petal of the second coil and the second electrical current flows in a counter-clockwise rotational direction in a second petal of the second coil.","7.The method of claim 1, further comprising energizing a plurality of coils at a frequency of 1-1000 Hz to generate an electrical field that delivers the first pulsed magnetic field, the second pulsed magnetic field and the third pulsed magnetic field.","8.The method of claim 1, further comprising energizing a plurality of coils with an electrical impulse of not less 100 μsmV/cm to deliver the first pulsed magnetic field, the second pulsed magnetic field and the third pulsed magnetic field.","9.The method of claim 1, further comprising: delivering the first pulsed magnetic field via a first coil; delivering the second pulsed magnetic field via a second coil; delivering the third pulsed magnetic field via a third coil; and arranging the first, second and third coils in a common plane.","10.The method of claim 9, further comprising arranging the first and second coils within a perimeter loop of the third coil.","11.The method of claim 10, further comprising forming each of the first and second coils to resemble a FIG.","8.12.The method of claim 9, further comprising forming each of the first and second coils to resemble a FIG.","8.13.The method of claim 1, further comprising providing heat input to the mammal sufficient to maintain a body surface temperature measurement in a range of 40-43 degree Celsius.","14.A method of treating chronic kidney disease of a mammal, the method comprising: delivering by a first coil a first pulsed magnetic field to a kidney of the mammal; delivering by a second coil a second pulsed magnetic field to the kidney of the mammal; and delivering by a third coil a third pulsed magnetic field to the kidney of the mammal; and arranging the first, second and third coils in a common plane.","15.The method of claim 14, further comprising arranging the first and second coils within a perimeter loop of the third coil.","16.The method of claim 14, further comprising configuring each of the first and second coils to resemble a FIG.","8.17.The method of claim 14, further comprising applying a treatment session to the kidney of the mammal on at least three days during a seven day period, wherein each treatment session includes the steps of delivering the first pulsed magnetic field, the second pulsed magnetic field and the third pulsed magnetic field to the kidney of the mammal for a duration of two to four hours.","18.The method of claim 14, further comprising applying a treatment session to the kidney of the mammal on at least three days during a seven day period, wherein each treatment session includes applying heat input to the mammal sufficient to maintain a body surface temperature measurement in a range of 40-43 degree Celsius.","19.A method of treating chronic kidney disease of a mammal, the method comprising: increasing a concentration of Ata adenosine receptors on cellular membranes in a kidney of the mammal by: applying a pulsed electromagnetic field (PEMF) treatment session to the kidney of the mammal on at least three days during a seven day period, wherein each PEMF treatment session includes the steps of delivering a first pulsed magnetic field, a second pulsed magnetic field and a third pulsed magnetic field to the kidney of the mammal for a duration of two to four hours; and applying an independent whole body heat stimulation to the mammal two to four times during the seven day period to induce heat shock proteins in the kidney of the mammal, wherein the first pulsed magnetic field is delivered via a first coil, wherein the second pulsed magnetic field is delivered via a second coil, wherein the third pulsed magnetic field is delivered via a third coil, and wherein each of the first, second and third coils are arranged in a common plane.","20.The method of claim 19, further comprising: arranging the first and second coils within a perimeter loop of the third coil; and orienting the second coil along an orthogonal axis that is ninety degrees offset from an orthogonal axis of the first coil."],[" BACKGROUND Kidneys are bean-shaped organs that serve as a biological filter removing metabolic waste from blood to the urinary bladder.","The basic structural and functional unit of kidney is a nephron, the main function of which is to regulate the concentration of water and soluble substances in blood, reabsorbing the vital elements and excreting the rest as urine.","In humans, a normal kidney contains 800,000 to 1.5 million nephrons.","The adequate kidney function is imperative for survival: kidneys control level of electrolytes in blood, regulate blood volume, blood pressure and blood pH.","Bacterial infections, accumulation of toxic materials and auto-immune diseases may cause inflammatory disease of kidneys, also called nephritis.","The symptoms of nephritis are a rise in blood pressure, back pain, edema and fatigue.","Albumin and other serum proteins in increasing quantities pass into urine, creating a condition called proteinuria.","If the condition continues to deteriorate, uremia or renal failure develops.","Renal failure leads to accumulation of high concentrations of metabolic waste in the blood and eventually causes death.","The conventional medical treatment is the removal of this waste by filtering blood with a dialysis machine, also called an artificial kidney.","When the condition deteriorates still further, transplantation of a kidney is the last and the only option.","Chronic kidney disease has several underlying reasons and involves the glomeruli, tubules or interstitial tissue surrounding the glomeruli and tubules.","The glomerulus is a network (tuft) of capillaries that performs the first step of blood filtration.","The renal tubule is the part of nephron containing the fluid filtered through the glomerulus.","Glomerulonephritis (GN) is inflammation of glomeruli.","GN may lead to serious kidney damage and, in some patients, kidney failure.","The causes of glomerulonephritis are complex and diverse, some have a genetic basis and others are associated with systemic diseases.","While treatment is available for some types of GN, many traditional therapies are toxic, non-specific and have the potential for major side effects.","Some GN subtypes do not respond to any therapies.","Worldwide, GN is the most common single cause of end-stage renal disease (ESRD).","There are more than 20 million Americans with chronic kidney disease and 50,000 of them die annually.","Though chronic autoimmune disorders such as systemic lupus erythematosus affect a significant percentage of the human population and strongly diminish the quality of life and life expectancy, the molecular mechanisms of those diseases are still poorly understood, hindering the development of novel treatment strategies.","Autoimmune diseases are caused by disturbed recognition of foreign and self-antigens, leading to the emergence of auto-reactive T-cells (so-called immunization phase).","T-cells are a major regulator of the inflammatory cascade.","The auto-reactive T-cells then trigger the second (so-called effector) phase of the disease which is characterized by activation of the immune cells that cause immune-mediated damage to host tissues.","For a long time, neutrophils have been neglected as potential players in the development of autoimmune diseases.","However, a significant amount of new experimental data suggests that neutrophils play an important role in both the immunization and the effector phase of autoimmune diseases.","Taken together, neutrophils should be considered as one of the most important cell types in autoimmune diseases and a suitable target for treatment of those diseases.","Neutrophils are the most common type of white blood cell in human body and are the first line of attack against invaders.","In a person with a healthy immune system, the white blood cells gather at an infected or injured site in the body and produce chemical substances that help fight off the infection.","These substances increase inflammatory reaction and attack invaders, causing some collateral injury to healthy tissue.","Usually the immune system is capable of producing additional substances that make the inflammatory process self-contained and limited in time.","Inflammation in a healthy individual usually signals that the immune system is responding appropriately to harmful invaders, damaged cells, irritants, or injury.","But, in case of autoimmune diseases, due to faulty interactions between blood and other immune system cells, the inflammation increases.","Attracted by cytokines (messenger molecules) expressed by activated endothelium and other residential cells in inflamed tissues, neutrophils, using “roll”, “stop” and “exit” mechanism leave blood vessels and congregate at a focus of infection.","Migrated into the kidney, neutrophils release their own cytokines, which in turn activate several other cell types and amplify inflammatory response.","In addition to recruiting and activating other cells of the immune system, neutrophils play a key role in the front-line defense against invading pathogens.","Neutrophils have three methods for directly attacking micro-organisms: phagocytosis, release of soluble anti-microbials substances, and generation of neutrophil extracellular traps (NETs).","NETs are networks of extracellular fibers, primarily composed of DNA from neutrophils, which bind and kill extracellular pathogens while minimizing damage to the host cells.","NETs may also have a deleterious effect on the host.","It is believed that excessive expression of extracellular histone complexes from DNA combined with their slow clearing plays an important role in the development of autoimmune kidney diseases, particular in lupus.","There is a need in developing of novel therapies that inhibit recruitment of neutrophils from blood vessels and deactivate neutrophils that already aggregated in kidneys.","The autoimmune diseases cause significant numbers of patients that progress to ESRD.","But the most important disease responsible for the highest number of patients with ESRD is diabetic nephropathy.","The growing epidemic of obesity-related insulin resistance and the difficulties in managing diabetes have made diabetic nephropathy the major single cause of kidney disease in the developed world.","Despite current clinical interventions involving tight glycemic and blood pressure control, diabetic nephropathy progresses in most patients with a significant proportion reaching end-stage renal failure.","In addition, the development of diabetic nephropathy exacerbates cardiovascular disease, which leads to increased morbidity and mortality.","Given the limited renal protection with current treatments, it is critical that alternative therapeutic approaches are developed to protect diabetic patients from diabetic kidney disease.","Recent studies have identified macrophage-mediated injury as an important component in the development of diabetic nephropathy that is not addressed by current therapies.","Further evidence has shown that macrophages are the major immune cells infiltrating the kidney in type 1 and type 2 diabetes, and that they contribute to the development of renal injury.","In view of this new evidence, diabetic nephropathy has been reclassified as a chronic inflammatory disease which is triggered and maintained by metabolic disturbances of diabetes mellitus.","Elements of the diabetic milieu activate the vascular endothelium, inducing increased expression of cell adhesion molecules (ICAM-1/VCAM-1) that adhere to circulating blood monocytes.","Using the “roll”, “stop” and “exit” sequence the blood monocytes migrate from the blood vessels to the kidney, where they differentiate into macrophages.","Glomerular podocytes, mesangial cells and tubular epithelial cells are also stimulated by the diabetic milieu.","They additionally secrete chemokines (MCP-1/OPN) that facilitate transendothelial and intrarenal monocytes/macrophage migration.","Also, the diabetic renal parenchymal cells produce colony stimulating factor-1 (CSF-1) which induces local proliferation of macrophages that also contributes to the accumulation of macrophages in diabetic kidneys.","Activated macrophages release reactive oxygen species and pro-inflammatory cytokines, which cause injury to podocytes, interstitial and tubular cells.","These macrophages also can secrete profibrotic cytokines that induce mesangial and fibroblast proliferation and development of fibrosis.","This ongoing renal injury and fibrosis promotes the progression of diabetic nephropathy.","Renal interstitial fibrosis (RIF) is the common pathological process of chronic kidney diseases leading inevitably to renal function deterioration.","RIF and preceding epithelial-mesenchymal transition (EMT) are commonly triggered in diabetic kidney by an early occurring renal inflammation.","However, an effective approach to prevent EMT and RIF is still lacking.","Adenosine A2a receptor recently emerged as a potent inflammation regulator.","Adenosine activation of A2a receptors suppresses the EMT process and protects kidneys against RIF.","Experimental studies suggest that activation of A2a significantly suppresses the deposition of collagen types I and III thus inhibiting the EMT progress.","As a result, activation of A2a effectively alleviates EMT and RIF, suggesting A2a receptors as a potential therapeutic target for treatment of RIF.","Development of therapeutic strategies for treatment of macrophage-mediated injury in kidney that selectively target mechanisms of macrophage recruitment, proliferation and activation seems to be an attractive choice in comparison with general immunosuppression.","Now it is commonly accepted that macrophages play a critical role in the development of diabetic nephropathy.","Current therapies, however, are unable to prevent the progressive renal damage caused by these inflammatory cells.","There is an urgent need for novel anti-inflammation and immuno-suppressive therapies aimed at reducing macrophage recruitment, accumulation and activation in diabetic kidneys.","Adenosine is a purine nucleoside generated by metabolically stressed or inflamed tissues that is recognized as a major endogenous anti-inflammatory regulator.","Under normal conditions, adenosine is continuously released from cells as a product of ATP degradation.","Adenosine concentration in extracellular space is controlled by an enzyme called adenosine deaminase (ADA) which breaks it down and keeps the concentration level in low-micromolar to high-nanomolar range.","However, during conditions of stress, such as hypoxia during inflammation, levels of extracellular adenosine rise dramatically (up to 200-fold).","This is partly due to increased production of AMP in hypoxic conditions, but substantial amounts of adenosine are also produced by the sequential dephosphorylation of adenine nucleotides released from platelets and hematopoietic cells, as well as damaged cells.","Adenosine regulates the function of the innate and adaptive immune systems through targeting virtually every cell type that is involved in orchestrating the immune/inflammatory response.","Of the four adenosine receptors (A1, A2a, A1b, A3), A2a receptors have taken center stage as the primary anti-inflammatory effectors of extracellular adenosine.","This broad, anti-inflammatory effect of A2a receptor activation is a result of the predominant expression of A2a receptors on monocytes/macrophages, dendritic cells, mast cells, neutrophils, endothelial cells, eosinophils, epithelial cells, as well as lymphocytes, NK cells, and NKT cells.","A2a receptors play a critical role in controlling leukocyte trafficking by suppressing release of cytokines that induce production of adhesion molecules (ICAM-1/VCAM-1) and promote the “roll”, “stop” and “exit” mechanism bringing neutrophils and monocytes/macrophages from blood vessels into tissues.","A2a receptor activation inhibits early and late events occurring during an immune response, which include immune cell trafficking, immune cell proliferation, proinflammatory cytokine production, and cytotoxicity.","In late stage of inflammation in addition to limiting inflammation, A2a receptors participate in tissue remodeling and restoration.","Consistent with their multifaceted, immunoregulatory action on immune cells, A2a receptors have been shown to impact the course of a wide spectrum of ischemic, autoimmune, infectious, and allergic diseases.","A2a receptors are found in all parenchymal cells in kidney: glomerular endothelium, podocytes, tubular endothelium and mesangial cells.","Adenosine A2a receptor activation was recently shown to be renoprotective in diabetic nephropathy.","Activated A2a receptors protect kidneys from diabetic nephropathy through actions on hematopoietic and kidney-derived cells.","Podocytes contribute to the maintenance of the glomerular filtration barrier and abnormalities of podocyte structure and function lead to a number of glomerular diseases.","Activation of adenosine A2a receptors preserves the structure and function of podocytes and leads to a reduction of proteinuria and preservation of glomerular function.","Macrophages play a critical role in immune response against pathogenic invaders.","Beyond increasing inflammation and stimulating the immune system, macrophages also play an important anti-inflammatory role and can decrease immune reactions through the release of cytokines.","Macrophages that encourage inflammation are called M1 macrophages, whereas those that decrease inflammation and encourage tissue repair are called M2 macrophages.","This difference is reflected in their metabolism, where macrophages have the unique ability to metabolize one amino acid, arginine, to either a “killer” molecule (nitric oxide) or a “repair” molecule (ornithine).","Macrophages morph in phenotypes M1 or M2 depending on the environment in which they are activated.","In the presence of cytokines such as IL-12 and IL-23 from T helper-1 cells that orchestrate initial stage of immune response, the “classically” activated macrophages are pro-inflammatory M1 type, whereas at the final stage of inflammation in presence of cytokine IL-10 and TGF-β from T helper-2 cells, macrophages become “alternatively” activated into anti-inflammation type M2, that promote tissue restoration.","The same macrophage that was a pro-inflammatory M1 type at the beginning of inflammation can be re-activated into an anti-inflammatory M2 type at the final stage of the inflammation.","Consistent with its generally restorative function in tissues, A2a receptor activation has been repeatedly shown to have effects that prevent excessive classical macrophage activation thereby resulting in tissue protection.","In contrast to the suppressive effect of adenosine on the production of proinflammatory mediators, adenosine augments production of anti-inflammatory cytokine IL-10 that promotes activation of macrophages into M2 type.","Thus, in addition to deactivating classically activated macrophages, A2a receptor signaling changes macrophage metabolism and enables switching their phenotype to alternative type M2 that participates in tissue restoration.","The protective effect of stimulation of A2a receptors was proven to correlate with decreased expression of adhesion molecules (ICAM-1/VCAM-1) and reduction of transmigration of neutrophil and monocytes/macrophages into the kidney.","In addition, the renal microvasculature responds to A2a receptors stimulation by vasodilation that results in increased blood flow in the renal microcirculation and contributes to the renal protection.","Pulsed Electromagnetic Field Therapy (PEMF) is a new non-invasive method of treatment of numerous medical conditions related to injuries and inflammations of different tissues: bones, cartilages, soft and neurological tissues.","For centuries it was a common knowledge that the natural wound healing involves generation of endogenous electric fields.","Recently it has been discovered that the endogenous electric fields control also the processes of remodeling and healing bones and cartilages.","In PEMF therapy the electric field is carried into the treatment zone by a pulsed magnetic field produced by electromagnetic coils from outside the body.","A PEMF system applies a series of magnetic pulses to injured tissue where each magnetic pulse induces an electrical signal that stimulates cellular anti-inflammatory and anabolic activities.","PEMF therapy reduces pain associated with inflammation by suppressing production of pain mediator prostaglandin E2 and accelerates natural healing of tissues.","Multiple studies have demonstrated effectiveness and safety of PEMF therapy in suppressing inflammation.","Recently it has been established by Varani et al.","that the anti-inflammation mechanism of action of PEMF on a cell is due to its ability to increase the concentration of receptors A2a on the cell membrane.","PEMF stimulation increases the number of active A2a receptors on the cell membrane by creating a conformational change of their protein and making them active and available for binding with adenosine ligand.","The signal to the cell and the biological response of the cell's machinery depends on both the concentration of ligands in extracellular space and the concentration of receptors on the cell membrane.","In other words, the magnitude of biological response of the cell depends on the product of these two concentrations.","As a result, the same response can be achieved by two different ways: by changing concentration of adenosine around the cell or by changing concentration of the receptors on the cell membrane.","The essence of the discovery of Varani et al.","is that the adenosine signaling pathway can be up-regulated without changing extracellular adenosine concentration.","It can be achieved by PEMF stimulation alone.","According to the experimental data, the A2a receptors can be up-regulated by the pulsed electric fields with amplitude above 50 μV/cm.","In the environment rich in extracellular adenosine, which is always the case with inflamed or stressed tissues, the up-regulation of A2a receptors leads to significant amplification of adenosine signaling.","PEMF stimulation triggers the same physiological response of the cell as an increase in concentration of adenosine or another A2a agonist in the extracellular space.","In either case, the magnitude of signal from A2a receptors to the cellular machinery increases as well as the downstream effects of the A2a signaling.","PEMF stimulation can affect a wide variety of cells that express A2a receptors, including T cells, macrophages, neutrophils and other lymphocytes.","All parenchymal kidney cells carry A2a receptors and can be stimulated by PEMF.","A2a receptors stimulated by PEMF are able to inhibit multiple processes occurring during an immune response, including immune cell trafficking and proliferation, pro-inflammatory cytokine production and cytotoxicity.","In addition to limiting inflammation, A2a receptors participate in tissue remodeling and repair.","A2a receptors have been shown to impact the course of autoimmune, infectious, and allergic diseases.","PEMF stimulation of A2a receptors generates immunosuppressive action by inhibiting overreactive immune cells, thereby protecting tissues from collateral inflammatory damage.","PEMF stimulation of A2a receptors provides a novel regulatory tool for immune/inflammatory diseases of various organs, including kidney.","They can be a critical part of the physiological negative feedback that limits local inflammatory responses.","Increased by PEMF stimulation, A2a signaling inhibits development of cytotoxicity and cytokine-producing activity in T-cells.","Stimulated by PEMF A2a receptors in autoreactive T-cells generate strong immunosuppressive action that reduces chronic inflammation and subsequent damage to the affected organ.","Upregulation of adenosine A2a signaling by PEMF in hematopoietic and renal parenchymal cells results in cascades of actions.","It can down-regulate recruitment of inflammatory leucocytes from blood vessels by acting on the vascular epithelial cell and disrupting the “roll”, “stop” and “exit” mechanism.","Via A2a receptors signaling PEMF promotes changing phenotypes of macrophages from pro-inflammatory type M1 to anti-inflammatory type M2, stimulates resolution of inflammation and tissue restoration.","It promotes improvement of function of podocytes, reduction of proteinuria, and down-regulation of expression of pro-inflammatory cytokines in mesangial cells—the major source of inflammation in diabetic kidney.","Also it inhibits renal interstitial fibrosis (RIF) by suppressing the epithelial-mesenchymal transition (EMT).","These outstanding anti-inflammation and immuno-suppressive actions of A2a receptors attracted attention of many researchers as a potential basis for development of new drugs for treatment of various inflammatory diseases.","Unfortunately, free adenosine has a very short half-life time in plasma, about 10 seconds, which severely limits its usage as a systemic drug.","However, a number of agonists with high selectivity to A2a receptors and long half-life in plasma have been developed recently, keeping the hope of developing these drugs alive.","It should be noticed that all new knowledge recently accumulated about A2a effects on the inflamed tissues came mainly from in vitro experiments and animal trials.","Unfortunately, in human clinical trials, a big problem with adenosine agonists has been encountered—a strong hemodynamic effect.","A2a receptors are abundantly expressed in vascular endothelium and play a significant role in regulating blood flow throughout the body.","Systemic activation of A2a receptors leads to vasodilation in the whole vascular bed and increases blood flow, which, in turn, creates a significant reactive drop in blood pressure, increase in heart rate and cardiac index.","These hemodynamic side effects limit systemic dosing of A2a agonists to the level at which they are no longer effective at resolution of inflammation.","This problem has contributed to the failure of several A2a agonists.","Examples of discontinued A2a agonists trials include GW328267X from GlaxoSmithKline PLC and UK-432097 from Pfizer Inc. Several A2a agonists, though, are still in clinical trials for inflammation-related indications.","The anti-inflammation and immuno-suppressive actions of A2a receptors can be employed by using PEMF stimulation of the affected areas.","For more than thirty years of experimental and clinical use of PEMF stimulation for different tissues there were no noticed side effects.","PEMF stimulation boosts activity of A2a receptors locally; it does not increase the concentration of adenosine around the cells, but instead, increases A2a concentration on the cellular membranes.","Local PEMF stimulation effects inflamed tissues only, where the concentration of adenosine is high, up to 200-fold of the base line.","As has been mentioned before, under normal physiological conditions concentration of adenosine in tissues is low and PEMF stimulation effects are minimal.","This is the major reason why PEMF therapy does not have side effects.","Stress response is one of the most important biological reactions to a wide variety of unfavorable physiological and environmental conditions.","It is a part of cell's own repair system that is evolutionary conserved and universally expressed from bacteria to humans.","One of the first cellular reactions on stress is rapid generation of so called heat shock proteins (HSPs).","Heat-shock proteins play numerous roles in cell function, including modulating protein activity by changing protein conformation, promoting multi-protein complex assembly/disassembly, regulating protein degradation within the proteasome pathway, facilitating protein translocation across organelle membranes, and ensuring proper folding of nascent polypeptide chains during protein translation.","When cells are overstressed, the common response is to undergo cell death by one of two pathways, either ‘necrosis’ or ‘apoptosis’.","Recently, both routes to cell death have been revealed to share similar mechanisms, with heat shock proteins and their cofactors responsible for inhibiting both apoptotic and necrotic pathways.","So, the effective biological function of HSPs is to preserve cell survival by maintaining the vital functions of proteins.","In practical terms, HSPs can be induced by local thermal stimulation with temperatures 40-43 degrees C. for 10-30 minutes.","Deep thermal stimulation can be achieved by ultrasound, high radiofrequency and microwave diathermia devices.","Also, kidneys can be stimulated as a part of the whole body thermal stimulation in a hot bath, sauna and steam room.","After thermal stimulation, intracellular concentration of HSPs rapidly grows to several fold level at 24 hours and returns to the basal level after 48-72 hours.","Intracellular buildup of HSPs is triggered by activation of Heat Shock Factor (HSF), whereas HSP concentration is controlled by enzyme adenosine deaminase (ADA) that degrades HSPs.","Luckily, the activity of ADA is inhibited by PEMF stimulation, so, as a result, PEMF helps to keep the HSPs concentration high.","It is known from animal studies that HSP72 inhibits proliferation and apoptosis in tubular cells and diminishes accumulation of fibroblasts and collagen in renal parenchyma, thus slowing the process of fibrosis.","It was also observed that HSP70 exerts strong cytoprotection of mesangial cells from oxidative injury in experiments with ischemic reperfusion.","Overall, a significant body of evidence suggests that HSPs delay the progression of chronic kidney disease (CKD) by the anti-apoptotic activity and cytoprotection.","Koga et al.","in the article “Mild electrical stimulation and heat shock ameliorates progressive proteinuria and renal inflammation in mouse model of Alport syndrome” demonstrated that combination of electrical and heat stimulation provides anti-proteinuric and anti-inflammatory effects on Alport mice through multiple signaling pathways via podocytic activation of Akt (protein kinase B) and induction of HSP72.The authors suggest a new therapeutic strategy to decelerate the progression of Alport syndrome by applying combined electrical and heat stimulation.","In the experiment described in the article, the electrical stimulation was provided by a pulsed direct electric current applied to the experimental animals via electrodes attached to the skin.","The thermal stimulation was delivered from the same electrodes.","In U.S. Pat.","No.","6,941,172 B2, issued to Zvi Nachum, a “Method and device for restoring kidney function using electromagnetic stimulation” is disclosed.","The method of restoring kidney function includes the steps of: (a) providing a device including: a conducting coil, and a signal generator for providing a plurality of electrical impulses to the coil; (b) disposing the conducting coil proximate to a kidney of a patient, and (c) delivering the electrical impulses conducted to the conducting coil, so as to produce an electromagnetic field, the electromagnetic field acting so as to stimulate the kidney.","The inventor states that this method is applicable only to the cases of acute kidney failure, mainly for traumatic ones, not to CKD: “The device and method of the present invention appear to be most effective in treating kidney failure due to trauma.","Kidney failure due to trauma is acute, and is generally reversible, at least during the initial stages.","Without wishing to be limited by theory, it is believed that a static charge builds up within the tissues of the kidney, for reasons that are not yet fully understood.","This static charge inhibits proper functioning of the kidney.","As long as no significant irreversible damage has been caused to the kidney, the kidney can be stimulated into regaining normal performance by clearing the static charge within the tissues of the kidney by application of an electromagnetic field using the device and method of the present invention”.","It should be mentioned that it is widely accepted in the art that the biologically active component of electromagnetic stimulation is the electric field produced by the changing magnetic field.","In the Nachum patent mentioned above, there is no disclosure of the magnitude of the electric field applied to the kidney.","But from the time dependency of the magnetic field which is described in the patent, it can be easy estimated that the electric field was about 1 μV/cm or less.","This level of electric field is, probably, enough to change the pathologic charging in the kidney caused by trauma, but it is not enough to up-regulate the A2a receptors on kidney cells.","In other words, the disclosed Nachum method, developed for restoration of kidney function of a traumatized kidney, cannot be effective in preservation of kidney function deteriorating due to chronic inflammation of kidney.","In particular, Nachum makes an explicit “distinction between acute and chronic renal failure is of cardinal importance” as explained in Column 1 starting at line 19 of his patent.","Chronic kidney disease and acute renal failure are clearly two different diseases.","Therefore, there continues to be a need for devices and methods for treating chronic kidney diseases."],[" SUMMARY The present invention effectively addresses certain drawbacks in the prior art kidney disease treatment devices and methods.","One object of certain embodiments is to provide PEMF stimulation for reduction of kidney inflammation and suppression of excessive immune response.","Another objective of certain embodiments is reduction of proteinuria, deceleration of progression of chronic kidney disease and preservation of kidney function.","Another objective of certain embodiments is to treat autoimmune diseases of kidneys.","Yet another objective of certain embodiments is to treat diabetic nephropathy.","Another objective of certain embodiments is to apply highly efficient PEMF stimulation to activate A2a receptors of parenchymal kidney cells and the immune cells accumulated in kidneys: T-cells, macrophages and neutrophils.","An objective of certain embodiments is to provide thermal stimulation to kidneys to increase vitality of kidney cells by induction of Heat Shock Proteins including HSP72 that inhibit apoptosis and necrosis of kidney cells.","Another objective of certain embodiments is to provide for treatment of kidneys a portable self-administered system that combines PEMF with thermal stimulations, which does not interfere with everyday activity and that can be used in office, home or in a car.","The aforementioned objectives can be achieved by providing a Thermally Assisted Pulse Electromagnetic Field (TA-PEMF) stimulation system that delivers both thermal and electric stimulation to kidneys.","The thermal stimulation is delivered by heating elements made of carbon fiber (CF) fabric secured to a belt that placed on the patient's back adjacent to kidneys.","The electric stimulation with enhanced efficiency is provided by three PEMF coils on each kidney, one is made as a flat spiral coil (Tesla coil) and two others are shaped in number 8 shape, one horizontal and one vertical.","Three coils and the heating element comprise a stimulation element that is secured to the belt adjacent to kidney.","The heating elements, controlled independently from PEMF coils, provide temperature at the surface of the body in the range of 40-43 degree C. that induces HSPs in kidneys.","The electrical stimulation, generated by PEMF coils, delivers rectangular electric pulses to kidneys with amplitudes, durations and frequencies that activate A2a receptors on both kidney-derived and immune cells.","The disclosure includes a method and apparatus for treatment of chronic kidney disease (CKD), particular diabetic nephropathy.","The method can include activation of adenosine A2a receptors in parenchymal and immune cells infiltrated into kidneys.","The activation is performed by PEMF (pulsed electromagnetic field) stimulation applied locally to kidneys.","Adenosine A2a signaling pathway is a potent anti-inflammatory and immuno-suppressive regulator that has been proven to attenuate inflammation and injury in diabetic nephropathy.","Efficient activation of A2a receptors is achieved by applying electromagnetic field stimulation consecutively in 3 spatial dimensions.","This allows attaining a significant increase in activation of A2a receptors in comparison with one-dimensional stimulation.","Assistant thermal stimulation may be applied to increase expression of heat shock proteins (HSPs) in parenchymal cells.","HSPs improve protein functions, protect cells from apoptosis and necrosis, increase metabolism, and symbiotically enhance effects of electric stimulation on CKD.","The disclosure includes a pulsed electromagnetic field therapy stimulation system for delivering treatment to a patient with chronic kidney disease.","The system includes an applicator and a first stimulation unit disposed in the applicator and located such that the first stimulation unit is disposed over a first kidney of the patient when the applicator is worn by the patient.","The first stimulation unit comprises a plurality of coils.","A first coil comprises a first petal and a second petal, the second petal extending longitudinally opposite the first petal along a first longitudinal axis, and defining a first coil crossover point where the first and second petals intersect.","A second coil comprises a first petal and a second petal, the second petal extending longitudinally opposite the first petal along a second longitudinal axis, and defining a second coil crossover point where the first and second petals intersect.","A third coil comprises a perimeter loop.","The first coil, second coil and third coil are disposed in a plane.","The first longitudinal axis is axially rotated ninety degrees with respect to the second longitudinal axis.","The first coil crossover point and second coil crossover point coincide.","The first coil and the second coil are disposed within the perimeter loop of the third coil.","The disclosure further includes a pulsed electromagnetic field therapy stimulator for treatment of chronic kidney disease in a patient.","The stimulator is coupled to a controller and a power source.","The controller is configured to selectively generate an electrical current to one or more coils.","The stimulator includes a first coil oriented along a first orthogonal axis.","The first coil comprises a first petal and a second petal.","The second petal extends longitudinally opposite the first petal such that an electrical current in the first petal flows in a first rotational direction and the electrical current in the second petal flows in a second rotational direction, wherein the second direction being opposite of the first direction.","The stimulator also includes a second coil oriented along a second orthogonal axis ninety degrees offset from the first orthogonal axis.","The second coil comprises a first petal and a second petal.","The second petal extends longitudinally opposite the first petal such that an electrical current in the first petal flows in a first rotational direction and the electrical current in the second petal flows in a second rotational direction, wherein the second direction being opposite of the first direction.","The first orthogonal axis and the second orthogonal axis lie in a common plane.","A third coil can also be provided.","The third coil comprises a loop disposed in the common plane and surrounds the first coil and the second coil.","The disclosure additionally includes a method of treating chronic kidney disease of a mammal.","The method includes increasing a concentration of Ata adenosine receptors on cellular membranes in a kidney of the mammal by delivering a first pulsed magnetic field with a first polarity to the kidney of the mammal along a first orthogonal direction.","A second pulsed magnetic field with the first polarity is delivered to the kidney of the mammal along a second orthogonal direction.","The second orthogonal direction is perpendicular to the first orthogonal direction.","The first and second orthogonal directions are also in a common plane.","A third pulsed magnetic field with the first polarity is further delivered to the kidney of the mammal along a third orthogonal direction.","The third orthogonal direction is perpendicular to the common plane.","The detailed technology and preferred embodiments implemented for the subject invention are described in the following paragraphs accompanying the appended drawings for people skilled in this field to well appreciate the features of the claimed invention.","It is understood that the features mentioned hereinbefore and those to be commented on hereinafter may be used not only in the specified combinations, but also in other combinations or in isolation, without departing from the scope of the present invention."],["PRIORITY This application is a divisional of U.S. patent application Ser.","No.","14/822,577, filed Aug. 10, 2015, which claims the priority benefit of U.S.","Provisional Patent Application Ser.","No.","61/999,921, filed Aug. 11, 2014, and both of which are hereby incorporated herein by reference in their entirety.","FIELD The invention relates to treatment of kidney disease.","More particularly, the invention relates to methods and apparatus for treating chronic kidney disease utilizing pulsed electromagnetic fields.","BACKGROUND Kidneys are bean-shaped organs that serve as a biological filter removing metabolic waste from blood to the urinary bladder.","The basic structural and functional unit of kidney is a nephron, the main function of which is to regulate the concentration of water and soluble substances in blood, reabsorbing the vital elements and excreting the rest as urine.","In humans, a normal kidney contains 800,000 to 1.5 million nephrons.","The adequate kidney function is imperative for survival: kidneys control level of electrolytes in blood, regulate blood volume, blood pressure and blood pH.","Bacterial infections, accumulation of toxic materials and auto-immune diseases may cause inflammatory disease of kidneys, also called nephritis.","The symptoms of nephritis are a rise in blood pressure, back pain, edema and fatigue.","Albumin and other serum proteins in increasing quantities pass into urine, creating a condition called proteinuria.","If the condition continues to deteriorate, uremia or renal failure develops.","Renal failure leads to accumulation of high concentrations of metabolic waste in the blood and eventually causes death.","The conventional medical treatment is the removal of this waste by filtering blood with a dialysis machine, also called an artificial kidney.","When the condition deteriorates still further, transplantation of a kidney is the last and the only option.","Chronic kidney disease has several underlying reasons and involves the glomeruli, tubules or interstitial tissue surrounding the glomeruli and tubules.","The glomerulus is a network (tuft) of capillaries that performs the first step of blood filtration.","The renal tubule is the part of nephron containing the fluid filtered through the glomerulus.","Glomerulonephritis (GN) is inflammation of glomeruli.","GN may lead to serious kidney damage and, in some patients, kidney failure.","The causes of glomerulonephritis are complex and diverse, some have a genetic basis and others are associated with systemic diseases.","While treatment is available for some types of GN, many traditional therapies are toxic, non-specific and have the potential for major side effects.","Some GN subtypes do not respond to any therapies.","Worldwide, GN is the most common single cause of end-stage renal disease (ESRD).","There are more than 20 million Americans with chronic kidney disease and 50,000 of them die annually.","Though chronic autoimmune disorders such as systemic lupus erythematosus affect a significant percentage of the human population and strongly diminish the quality of life and life expectancy, the molecular mechanisms of those diseases are still poorly understood, hindering the development of novel treatment strategies.","Autoimmune diseases are caused by disturbed recognition of foreign and self-antigens, leading to the emergence of auto-reactive T-cells (so-called immunization phase).","T-cells are a major regulator of the inflammatory cascade.","The auto-reactive T-cells then trigger the second (so-called effector) phase of the disease which is characterized by activation of the immune cells that cause immune-mediated damage to host tissues.","For a long time, neutrophils have been neglected as potential players in the development of autoimmune diseases.","However, a significant amount of new experimental data suggests that neutrophils play an important role in both the immunization and the effector phase of autoimmune diseases.","Taken together, neutrophils should be considered as one of the most important cell types in autoimmune diseases and a suitable target for treatment of those diseases.","Neutrophils are the most common type of white blood cell in human body and are the first line of attack against invaders.","In a person with a healthy immune system, the white blood cells gather at an infected or injured site in the body and produce chemical substances that help fight off the infection.","These substances increase inflammatory reaction and attack invaders, causing some collateral injury to healthy tissue.","Usually the immune system is capable of producing additional substances that make the inflammatory process self-contained and limited in time.","Inflammation in a healthy individual usually signals that the immune system is responding appropriately to harmful invaders, damaged cells, irritants, or injury.","But, in case of autoimmune diseases, due to faulty interactions between blood and other immune system cells, the inflammation increases.","Attracted by cytokines (messenger molecules) expressed by activated endothelium and other residential cells in inflamed tissues, neutrophils, using “roll”, “stop” and “exit” mechanism leave blood vessels and congregate at a focus of infection.","Migrated into the kidney, neutrophils release their own cytokines, which in turn activate several other cell types and amplify inflammatory response.","In addition to recruiting and activating other cells of the immune system, neutrophils play a key role in the front-line defense against invading pathogens.","Neutrophils have three methods for directly attacking micro-organisms: phagocytosis, release of soluble anti-microbials substances, and generation of neutrophil extracellular traps (NETs).","NETs are networks of extracellular fibers, primarily composed of DNA from neutrophils, which bind and kill extracellular pathogens while minimizing damage to the host cells.","NETs may also have a deleterious effect on the host.","It is believed that excessive expression of extracellular histone complexes from DNA combined with their slow clearing plays an important role in the development of autoimmune kidney diseases, particular in lupus.","There is a need in developing of novel therapies that inhibit recruitment of neutrophils from blood vessels and deactivate neutrophils that already aggregated in kidneys.","The autoimmune diseases cause significant numbers of patients that progress to ESRD.","But the most important disease responsible for the highest number of patients with ESRD is diabetic nephropathy.","The growing epidemic of obesity-related insulin resistance and the difficulties in managing diabetes have made diabetic nephropathy the major single cause of kidney disease in the developed world.","Despite current clinical interventions involving tight glycemic and blood pressure control, diabetic nephropathy progresses in most patients with a significant proportion reaching end-stage renal failure.","In addition, the development of diabetic nephropathy exacerbates cardiovascular disease, which leads to increased morbidity and mortality.","Given the limited renal protection with current treatments, it is critical that alternative therapeutic approaches are developed to protect diabetic patients from diabetic kidney disease.","Recent studies have identified macrophage-mediated injury as an important component in the development of diabetic nephropathy that is not addressed by current therapies.","Further evidence has shown that macrophages are the major immune cells infiltrating the kidney in type 1 and type 2 diabetes, and that they contribute to the development of renal injury.","In view of this new evidence, diabetic nephropathy has been reclassified as a chronic inflammatory disease which is triggered and maintained by metabolic disturbances of diabetes mellitus.","Elements of the diabetic milieu activate the vascular endothelium, inducing increased expression of cell adhesion molecules (ICAM-1/VCAM-1) that adhere to circulating blood monocytes.","Using the “roll”, “stop” and “exit” sequence the blood monocytes migrate from the blood vessels to the kidney, where they differentiate into macrophages.","Glomerular podocytes, mesangial cells and tubular epithelial cells are also stimulated by the diabetic milieu.","They additionally secrete chemokines (MCP-1/OPN) that facilitate transendothelial and intrarenal monocytes/macrophage migration.","Also, the diabetic renal parenchymal cells produce colony stimulating factor-1 (CSF-1) which induces local proliferation of macrophages that also contributes to the accumulation of macrophages in diabetic kidneys.","Activated macrophages release reactive oxygen species and pro-inflammatory cytokines, which cause injury to podocytes, interstitial and tubular cells.","These macrophages also can secrete profibrotic cytokines that induce mesangial and fibroblast proliferation and development of fibrosis.","This ongoing renal injury and fibrosis promotes the progression of diabetic nephropathy.","Renal interstitial fibrosis (RIF) is the common pathological process of chronic kidney diseases leading inevitably to renal function deterioration.","RIF and preceding epithelial-mesenchymal transition (EMT) are commonly triggered in diabetic kidney by an early occurring renal inflammation.","However, an effective approach to prevent EMT and RIF is still lacking.","Adenosine A2a receptor recently emerged as a potent inflammation regulator.","Adenosine activation of A2a receptors suppresses the EMT process and protects kidneys against RIF.","Experimental studies suggest that activation of A2a significantly suppresses the deposition of collagen types I and III thus inhibiting the EMT progress.","As a result, activation of A2a effectively alleviates EMT and RIF, suggesting A2a receptors as a potential therapeutic target for treatment of RIF.","Development of therapeutic strategies for treatment of macrophage-mediated injury in kidney that selectively target mechanisms of macrophage recruitment, proliferation and activation seems to be an attractive choice in comparison with general immunosuppression.","Now it is commonly accepted that macrophages play a critical role in the development of diabetic nephropathy.","Current therapies, however, are unable to prevent the progressive renal damage caused by these inflammatory cells.","There is an urgent need for novel anti-inflammation and immuno-suppressive therapies aimed at reducing macrophage recruitment, accumulation and activation in diabetic kidneys.","Adenosine is a purine nucleoside generated by metabolically stressed or inflamed tissues that is recognized as a major endogenous anti-inflammatory regulator.","Under normal conditions, adenosine is continuously released from cells as a product of ATP degradation.","Adenosine concentration in extracellular space is controlled by an enzyme called adenosine deaminase (ADA) which breaks it down and keeps the concentration level in low-micromolar to high-nanomolar range.","However, during conditions of stress, such as hypoxia during inflammation, levels of extracellular adenosine rise dramatically (up to 200-fold).","This is partly due to increased production of AMP in hypoxic conditions, but substantial amounts of adenosine are also produced by the sequential dephosphorylation of adenine nucleotides released from platelets and hematopoietic cells, as well as damaged cells.","Adenosine regulates the function of the innate and adaptive immune systems through targeting virtually every cell type that is involved in orchestrating the immune/inflammatory response.","Of the four adenosine receptors (A1, A2a, A1b, A3), A2a receptors have taken center stage as the primary anti-inflammatory effectors of extracellular adenosine.","This broad, anti-inflammatory effect of A2a receptor activation is a result of the predominant expression of A2a receptors on monocytes/macrophages, dendritic cells, mast cells, neutrophils, endothelial cells, eosinophils, epithelial cells, as well as lymphocytes, NK cells, and NKT cells.","A2a receptors play a critical role in controlling leukocyte trafficking by suppressing release of cytokines that induce production of adhesion molecules (ICAM-1/VCAM-1) and promote the “roll”, “stop” and “exit” mechanism bringing neutrophils and monocytes/macrophages from blood vessels into tissues.","A2a receptor activation inhibits early and late events occurring during an immune response, which include immune cell trafficking, immune cell proliferation, proinflammatory cytokine production, and cytotoxicity.","In late stage of inflammation in addition to limiting inflammation, A2a receptors participate in tissue remodeling and restoration.","Consistent with their multifaceted, immunoregulatory action on immune cells, A2a receptors have been shown to impact the course of a wide spectrum of ischemic, autoimmune, infectious, and allergic diseases.","A2a receptors are found in all parenchymal cells in kidney: glomerular endothelium, podocytes, tubular endothelium and mesangial cells.","Adenosine A2a receptor activation was recently shown to be renoprotective in diabetic nephropathy.","Activated A2a receptors protect kidneys from diabetic nephropathy through actions on hematopoietic and kidney-derived cells.","Podocytes contribute to the maintenance of the glomerular filtration barrier and abnormalities of podocyte structure and function lead to a number of glomerular diseases.","Activation of adenosine A2a receptors preserves the structure and function of podocytes and leads to a reduction of proteinuria and preservation of glomerular function.","Macrophages play a critical role in immune response against pathogenic invaders.","Beyond increasing inflammation and stimulating the immune system, macrophages also play an important anti-inflammatory role and can decrease immune reactions through the release of cytokines.","Macrophages that encourage inflammation are called M1 macrophages, whereas those that decrease inflammation and encourage tissue repair are called M2 macrophages.","This difference is reflected in their metabolism, where macrophages have the unique ability to metabolize one amino acid, arginine, to either a “killer” molecule (nitric oxide) or a “repair” molecule (ornithine).","Macrophages morph in phenotypes M1 or M2 depending on the environment in which they are activated.","In the presence of cytokines such as IL-12 and IL-23 from T helper-1 cells that orchestrate initial stage of immune response, the “classically” activated macrophages are pro-inflammatory M1 type, whereas at the final stage of inflammation in presence of cytokine IL-10 and TGF-β from T helper-2 cells, macrophages become “alternatively” activated into anti-inflammation type M2, that promote tissue restoration.","The same macrophage that was a pro-inflammatory M1 type at the beginning of inflammation can be re-activated into an anti-inflammatory M2 type at the final stage of the inflammation.","Consistent with its generally restorative function in tissues, A2a receptor activation has been repeatedly shown to have effects that prevent excessive classical macrophage activation thereby resulting in tissue protection.","In contrast to the suppressive effect of adenosine on the production of proinflammatory mediators, adenosine augments production of anti-inflammatory cytokine IL-10 that promotes activation of macrophages into M2 type.","Thus, in addition to deactivating classically activated macrophages, A2a receptor signaling changes macrophage metabolism and enables switching their phenotype to alternative type M2 that participates in tissue restoration.","The protective effect of stimulation of A2a receptors was proven to correlate with decreased expression of adhesion molecules (ICAM-1/VCAM-1) and reduction of transmigration of neutrophil and monocytes/macrophages into the kidney.","In addition, the renal microvasculature responds to A2a receptors stimulation by vasodilation that results in increased blood flow in the renal microcirculation and contributes to the renal protection.","Pulsed Electromagnetic Field Therapy (PEMF) is a new non-invasive method of treatment of numerous medical conditions related to injuries and inflammations of different tissues: bones, cartilages, soft and neurological tissues.","For centuries it was a common knowledge that the natural wound healing involves generation of endogenous electric fields.","Recently it has been discovered that the endogenous electric fields control also the processes of remodeling and healing bones and cartilages.","In PEMF therapy the electric field is carried into the treatment zone by a pulsed magnetic field produced by electromagnetic coils from outside the body.","A PEMF system applies a series of magnetic pulses to injured tissue where each magnetic pulse induces an electrical signal that stimulates cellular anti-inflammatory and anabolic activities.","PEMF therapy reduces pain associated with inflammation by suppressing production of pain mediator prostaglandin E2 and accelerates natural healing of tissues.","Multiple studies have demonstrated effectiveness and safety of PEMF therapy in suppressing inflammation.","Recently it has been established by Varani et al.","that the anti-inflammation mechanism of action of PEMF on a cell is due to its ability to increase the concentration of receptors A2a on the cell membrane.","PEMF stimulation increases the number of active A2a receptors on the cell membrane by creating a conformational change of their protein and making them active and available for binding with adenosine ligand.","The signal to the cell and the biological response of the cell's machinery depends on both the concentration of ligands in extracellular space and the concentration of receptors on the cell membrane.","In other words, the magnitude of biological response of the cell depends on the product of these two concentrations.","As a result, the same response can be achieved by two different ways: by changing concentration of adenosine around the cell or by changing concentration of the receptors on the cell membrane.","The essence of the discovery of Varani et al.","is that the adenosine signaling pathway can be up-regulated without changing extracellular adenosine concentration.","It can be achieved by PEMF stimulation alone.","According to the experimental data, the A2a receptors can be up-regulated by the pulsed electric fields with amplitude above 50 μV/cm.","In the environment rich in extracellular adenosine, which is always the case with inflamed or stressed tissues, the up-regulation of A2a receptors leads to significant amplification of adenosine signaling.","PEMF stimulation triggers the same physiological response of the cell as an increase in concentration of adenosine or another A2a agonist in the extracellular space.","In either case, the magnitude of signal from A2a receptors to the cellular machinery increases as well as the downstream effects of the A2a signaling.","PEMF stimulation can affect a wide variety of cells that express A2a receptors, including T cells, macrophages, neutrophils and other lymphocytes.","All parenchymal kidney cells carry A2a receptors and can be stimulated by PEMF.","A2a receptors stimulated by PEMF are able to inhibit multiple processes occurring during an immune response, including immune cell trafficking and proliferation, pro-inflammatory cytokine production and cytotoxicity.","In addition to limiting inflammation, A2a receptors participate in tissue remodeling and repair.","A2a receptors have been shown to impact the course of autoimmune, infectious, and allergic diseases.","PEMF stimulation of A2a receptors generates immunosuppressive action by inhibiting overreactive immune cells, thereby protecting tissues from collateral inflammatory damage.","PEMF stimulation of A2a receptors provides a novel regulatory tool for immune/inflammatory diseases of various organs, including kidney.","They can be a critical part of the physiological negative feedback that limits local inflammatory responses.","Increased by PEMF stimulation, A2a signaling inhibits development of cytotoxicity and cytokine-producing activity in T-cells.","Stimulated by PEMF A2a receptors in autoreactive T-cells generate strong immunosuppressive action that reduces chronic inflammation and subsequent damage to the affected organ.","Upregulation of adenosine A2a signaling by PEMF in hematopoietic and renal parenchymal cells results in cascades of actions.","It can down-regulate recruitment of inflammatory leucocytes from blood vessels by acting on the vascular epithelial cell and disrupting the “roll”, “stop” and “exit” mechanism.","Via A2a receptors signaling PEMF promotes changing phenotypes of macrophages from pro-inflammatory type M1 to anti-inflammatory type M2, stimulates resolution of inflammation and tissue restoration.","It promotes improvement of function of podocytes, reduction of proteinuria, and down-regulation of expression of pro-inflammatory cytokines in mesangial cells—the major source of inflammation in diabetic kidney.","Also it inhibits renal interstitial fibrosis (RIF) by suppressing the epithelial-mesenchymal transition (EMT).","These outstanding anti-inflammation and immuno-suppressive actions of A2a receptors attracted attention of many researchers as a potential basis for development of new drugs for treatment of various inflammatory diseases.","Unfortunately, free adenosine has a very short half-life time in plasma, about 10 seconds, which severely limits its usage as a systemic drug.","However, a number of agonists with high selectivity to A2a receptors and long half-life in plasma have been developed recently, keeping the hope of developing these drugs alive.","It should be noticed that all new knowledge recently accumulated about A2a effects on the inflamed tissues came mainly from in vitro experiments and animal trials.","Unfortunately, in human clinical trials, a big problem with adenosine agonists has been encountered—a strong hemodynamic effect.","A2a receptors are abundantly expressed in vascular endothelium and play a significant role in regulating blood flow throughout the body.","Systemic activation of A2a receptors leads to vasodilation in the whole vascular bed and increases blood flow, which, in turn, creates a significant reactive drop in blood pressure, increase in heart rate and cardiac index.","These hemodynamic side effects limit systemic dosing of A2a agonists to the level at which they are no longer effective at resolution of inflammation.","This problem has contributed to the failure of several A2a agonists.","Examples of discontinued A2a agonists trials include GW328267X from GlaxoSmithKline PLC and UK-432097 from Pfizer Inc. Several A2a agonists, though, are still in clinical trials for inflammation-related indications.","The anti-inflammation and immuno-suppressive actions of A2a receptors can be employed by using PEMF stimulation of the affected areas.","For more than thirty years of experimental and clinical use of PEMF stimulation for different tissues there were no noticed side effects.","PEMF stimulation boosts activity of A2a receptors locally; it does not increase the concentration of adenosine around the cells, but instead, increases A2a concentration on the cellular membranes.","Local PEMF stimulation effects inflamed tissues only, where the concentration of adenosine is high, up to 200-fold of the base line.","As has been mentioned before, under normal physiological conditions concentration of adenosine in tissues is low and PEMF stimulation effects are minimal.","This is the major reason why PEMF therapy does not have side effects.","Stress response is one of the most important biological reactions to a wide variety of unfavorable physiological and environmental conditions.","It is a part of cell's own repair system that is evolutionary conserved and universally expressed from bacteria to humans.","One of the first cellular reactions on stress is rapid generation of so called heat shock proteins (HSPs).","Heat-shock proteins play numerous roles in cell function, including modulating protein activity by changing protein conformation, promoting multi-protein complex assembly/disassembly, regulating protein degradation within the proteasome pathway, facilitating protein translocation across organelle membranes, and ensuring proper folding of nascent polypeptide chains during protein translation.","When cells are overstressed, the common response is to undergo cell death by one of two pathways, either ‘necrosis’ or ‘apoptosis’.","Recently, both routes to cell death have been revealed to share similar mechanisms, with heat shock proteins and their cofactors responsible for inhibiting both apoptotic and necrotic pathways.","So, the effective biological function of HSPs is to preserve cell survival by maintaining the vital functions of proteins.","In practical terms, HSPs can be induced by local thermal stimulation with temperatures 40-43 degrees C. for 10-30 minutes.","Deep thermal stimulation can be achieved by ultrasound, high radiofrequency and microwave diathermia devices.","Also, kidneys can be stimulated as a part of the whole body thermal stimulation in a hot bath, sauna and steam room.","After thermal stimulation, intracellular concentration of HSPs rapidly grows to several fold level at 24 hours and returns to the basal level after 48-72 hours.","Intracellular buildup of HSPs is triggered by activation of Heat Shock Factor (HSF), whereas HSP concentration is controlled by enzyme adenosine deaminase (ADA) that degrades HSPs.","Luckily, the activity of ADA is inhibited by PEMF stimulation, so, as a result, PEMF helps to keep the HSPs concentration high.","It is known from animal studies that HSP72 inhibits proliferation and apoptosis in tubular cells and diminishes accumulation of fibroblasts and collagen in renal parenchyma, thus slowing the process of fibrosis.","It was also observed that HSP70 exerts strong cytoprotection of mesangial cells from oxidative injury in experiments with ischemic reperfusion.","Overall, a significant body of evidence suggests that HSPs delay the progression of chronic kidney disease (CKD) by the anti-apoptotic activity and cytoprotection.","Koga et al.","in the article “Mild electrical stimulation and heat shock ameliorates progressive proteinuria and renal inflammation in mouse model of Alport syndrome” demonstrated that combination of electrical and heat stimulation provides anti-proteinuric and anti-inflammatory effects on Alport mice through multiple signaling pathways via podocytic activation of Akt (protein kinase B) and induction of HSP72.The authors suggest a new therapeutic strategy to decelerate the progression of Alport syndrome by applying combined electrical and heat stimulation.","In the experiment described in the article, the electrical stimulation was provided by a pulsed direct electric current applied to the experimental animals via electrodes attached to the skin.","The thermal stimulation was delivered from the same electrodes.","In U.S. Pat.","No.","6,941,172 B2, issued to Zvi Nachum, a “Method and device for restoring kidney function using electromagnetic stimulation” is disclosed.","The method of restoring kidney function includes the steps of: (a) providing a device including: a conducting coil, and a signal generator for providing a plurality of electrical impulses to the coil; (b) disposing the conducting coil proximate to a kidney of a patient, and (c) delivering the electrical impulses conducted to the conducting coil, so as to produce an electromagnetic field, the electromagnetic field acting so as to stimulate the kidney.","The inventor states that this method is applicable only to the cases of acute kidney failure, mainly for traumatic ones, not to CKD: “The device and method of the present invention appear to be most effective in treating kidney failure due to trauma.","Kidney failure due to trauma is acute, and is generally reversible, at least during the initial stages.","Without wishing to be limited by theory, it is believed that a static charge builds up within the tissues of the kidney, for reasons that are not yet fully understood.","This static charge inhibits proper functioning of the kidney.","As long as no significant irreversible damage has been caused to the kidney, the kidney can be stimulated into regaining normal performance by clearing the static charge within the tissues of the kidney by application of an electromagnetic field using the device and method of the present invention”.","It should be mentioned that it is widely accepted in the art that the biologically active component of electromagnetic stimulation is the electric field produced by the changing magnetic field.","In the Nachum patent mentioned above, there is no disclosure of the magnitude of the electric field applied to the kidney.","But from the time dependency of the magnetic field which is described in the patent, it can be easy estimated that the electric field was about 1 μV/cm or less.","This level of electric field is, probably, enough to change the pathologic charging in the kidney caused by trauma, but it is not enough to up-regulate the A2a receptors on kidney cells.","In other words, the disclosed Nachum method, developed for restoration of kidney function of a traumatized kidney, cannot be effective in preservation of kidney function deteriorating due to chronic inflammation of kidney.","In particular, Nachum makes an explicit “distinction between acute and chronic renal failure is of cardinal importance” as explained in Column 1 starting at line 19 of his patent.","Chronic kidney disease and acute renal failure are clearly two different diseases.","Therefore, there continues to be a need for devices and methods for treating chronic kidney diseases.","SUMMARY The present invention effectively addresses certain drawbacks in the prior art kidney disease treatment devices and methods.","One object of certain embodiments is to provide PEMF stimulation for reduction of kidney inflammation and suppression of excessive immune response.","Another objective of certain embodiments is reduction of proteinuria, deceleration of progression of chronic kidney disease and preservation of kidney function.","Another objective of certain embodiments is to treat autoimmune diseases of kidneys.","Yet another objective of certain embodiments is to treat diabetic nephropathy.","Another objective of certain embodiments is to apply highly efficient PEMF stimulation to activate A2a receptors of parenchymal kidney cells and the immune cells accumulated in kidneys: T-cells, macrophages and neutrophils.","An objective of certain embodiments is to provide thermal stimulation to kidneys to increase vitality of kidney cells by induction of Heat Shock Proteins including HSP72 that inhibit apoptosis and necrosis of kidney cells.","Another objective of certain embodiments is to provide for treatment of kidneys a portable self-administered system that combines PEMF with thermal stimulations, which does not interfere with everyday activity and that can be used in office, home or in a car.","The aforementioned objectives can be achieved by providing a Thermally Assisted Pulse Electromagnetic Field (TA-PEMF) stimulation system that delivers both thermal and electric stimulation to kidneys.","The thermal stimulation is delivered by heating elements made of carbon fiber (CF) fabric secured to a belt that placed on the patient's back adjacent to kidneys.","The electric stimulation with enhanced efficiency is provided by three PEMF coils on each kidney, one is made as a flat spiral coil (Tesla coil) and two others are shaped in number 8 shape, one horizontal and one vertical.","Three coils and the heating element comprise a stimulation element that is secured to the belt adjacent to kidney.","The heating elements, controlled independently from PEMF coils, provide temperature at the surface of the body in the range of 40-43 degree C. that induces HSPs in kidneys.","The electrical stimulation, generated by PEMF coils, delivers rectangular electric pulses to kidneys with amplitudes, durations and frequencies that activate A2a receptors on both kidney-derived and immune cells.","The disclosure includes a method and apparatus for treatment of chronic kidney disease (CKD), particular diabetic nephropathy.","The method can include activation of adenosine A2a receptors in parenchymal and immune cells infiltrated into kidneys.","The activation is performed by PEMF (pulsed electromagnetic field) stimulation applied locally to kidneys.","Adenosine A2a signaling pathway is a potent anti-inflammatory and immuno-suppressive regulator that has been proven to attenuate inflammation and injury in diabetic nephropathy.","Efficient activation of A2a receptors is achieved by applying electromagnetic field stimulation consecutively in 3 spatial dimensions.","This allows attaining a significant increase in activation of A2a receptors in comparison with one-dimensional stimulation.","Assistant thermal stimulation may be applied to increase expression of heat shock proteins (HSPs) in parenchymal cells.","HSPs improve protein functions, protect cells from apoptosis and necrosis, increase metabolism, and symbiotically enhance effects of electric stimulation on CKD.","The disclosure includes a pulsed electromagnetic field therapy stimulation system for delivering treatment to a patient with chronic kidney disease.","The system includes an applicator and a first stimulation unit disposed in the applicator and located such that the first stimulation unit is disposed over a first kidney of the patient when the applicator is worn by the patient.","The first stimulation unit comprises a plurality of coils.","A first coil comprises a first petal and a second petal, the second petal extending longitudinally opposite the first petal along a first longitudinal axis, and defining a first coil crossover point where the first and second petals intersect.","A second coil comprises a first petal and a second petal, the second petal extending longitudinally opposite the first petal along a second longitudinal axis, and defining a second coil crossover point where the first and second petals intersect.","A third coil comprises a perimeter loop.","The first coil, second coil and third coil are disposed in a plane.","The first longitudinal axis is axially rotated ninety degrees with respect to the second longitudinal axis.","The first coil crossover point and second coil crossover point coincide.","The first coil and the second coil are disposed within the perimeter loop of the third coil.","The disclosure further includes a pulsed electromagnetic field therapy stimulator for treatment of chronic kidney disease in a patient.","The stimulator is coupled to a controller and a power source.","The controller is configured to selectively generate an electrical current to one or more coils.","The stimulator includes a first coil oriented along a first orthogonal axis.","The first coil comprises a first petal and a second petal.","The second petal extends longitudinally opposite the first petal such that an electrical current in the first petal flows in a first rotational direction and the electrical current in the second petal flows in a second rotational direction, wherein the second direction being opposite of the first direction.","The stimulator also includes a second coil oriented along a second orthogonal axis ninety degrees offset from the first orthogonal axis.","The second coil comprises a first petal and a second petal.","The second petal extends longitudinally opposite the first petal such that an electrical current in the first petal flows in a first rotational direction and the electrical current in the second petal flows in a second rotational direction, wherein the second direction being opposite of the first direction.","The first orthogonal axis and the second orthogonal axis lie in a common plane.","A third coil can also be provided.","The third coil comprises a loop disposed in the common plane and surrounds the first coil and the second coil.","The disclosure additionally includes a method of treating chronic kidney disease of a mammal.","The method includes increasing a concentration of Ata adenosine receptors on cellular membranes in a kidney of the mammal by delivering a first pulsed magnetic field with a first polarity to the kidney of the mammal along a first orthogonal direction.","A second pulsed magnetic field with the first polarity is delivered to the kidney of the mammal along a second orthogonal direction.","The second orthogonal direction is perpendicular to the first orthogonal direction.","The first and second orthogonal directions are also in a common plane.","A third pulsed magnetic field with the first polarity is further delivered to the kidney of the mammal along a third orthogonal direction.","The third orthogonal direction is perpendicular to the common plane.","The detailed technology and preferred embodiments implemented for the subject invention are described in the following paragraphs accompanying the appended drawings for people skilled in this field to well appreciate the features of the claimed invention.","It is understood that the features mentioned hereinbefore and those to be commented on hereinafter may be used not only in the specified combinations, but also in other combinations or in isolation, without departing from the scope of the present invention.","BRIEF DESCRIPTION OF THE DRAWINGS FIG.","1 is a PEMF system for treatment of a kidney according to an example embodiment.","FIG.","2 is a schematic of a TA-PEMF stimulation unit according to an example embodiment.","FIG.","3a is a schematic of a heater for a TA-PEMF stimulation unit according to an example embodiment.","FIG.","3b is a schematic of another heater for a TA-PEMF stimulation unit according to an example embodiment.","FIG.","4 is a schematic of a stimulation unit according to an example embodiment.","FIGS.","5a, 5b and 5c are diagrams of PEMF stimulation of kidney according to an example embodiment.","FIG.","6a is a diagram of the interaction of adenosine receptors with the electric field due to PEMF stimulation of the kidney according to an example embodiment where the cell is shown without electric field.","FIG.","6b is a diagram of the interaction of adenosine receptors with the electric field due to PEMF stimulation of the kidney according to an example embodiment where the cell is shown in electrical field E. FIG.","7 is a series of diagrams illustrating application of stimulating Ex, Ey and Ez electric fields according to an example embodiment.","FIG.","8 is a series of diagrams illustrating voltage (a), current and magnetic field (b), electric field (c) and thermal pulses (d and e) used in a PEMP stimulation apparatus according to an example embodiment.","While the invention is amenable to various modifications and alternative forms, specifics thereof have been shown by way of example in the drawings and will be described in detail.","It should be understood, however, that the intention is not to limit the invention to the particular example embodiments described.","On the contrary, the invention is to cover all modifications, equivalents, and alternatives falling within the scope of the invention as defined by the appended claims.","DETAILED DESCRIPTION In the following descriptions, the present invention will be explained with reference to various example embodiments; nevertheless, these example embodiments are not intended to limit the present invention to any specific example, embodiment, environment, application, or particular implementation described herein.","Therefore, descriptions of these example embodiments are only provided for purpose of illustration rather than to limit the present invention.","An embodiment of a method and apparatus for treatment of chronic kidney disease is illustrated by FIG.","1.The TA-PEMF stimulation system 100 for treatment of chronic kidney disease is shown with reference to the back 101 side of the patient.","An applicator 102 such as a belt attachable to the back of the patient is secured adjacent to the patient and arranged such that a first TA-PEMF stimulation unit 103 is disposed over the left kidney and a second TA-PEMF stimulation unit 104 is disposed over the right kidney.","Electrical conduits 105 connect the first and second TA-PEMF stimulation units.","The stimulation units 103, 104 can be connected in series, as shown in FIG.","1, or in parallel to each other.","Additional electrical conduits 106 and 107 connect both stimulating units 103 and 104 to conduit 108 and further to a controller 109.The controller 109 is a computerized control unit, including both a processor and memory, to control the power and operation of the stimulation units disposed in the applicator 102.The controller 109 further includes a display 110, and on/off control button 111 and temperature indicator 112 (e.g.","a bar indicator, digital numerical display, sequential LEDs or other similar indication means).","Rotation of button 111 allows user to select a desired level of treatment temperature within permissible boundaries.","A power cable 113 or conduit connects controller 109 to power supply 114, which can be a battery or DC power supply connected to an AC power outlet.","The power supply can also be combined with controller into a single integrated housing.","FIG.","2 schematically depicts a TA-PEMF stimulation unit 200.A flat resistive heater 201 made of flexible carbon fiber fabric (CF) is provided.","Conductive electrodes 203 and 204 are connected to the resistive CF heater 201 and to controller 109 by respective wires 205 and 206.A thermal sensor 207 is secured on heater 201 and is functionally connected to controller 109 by a pair of wires 208.Controller 109 provides DC pulsed power to heater 201.These pulses can be short, long, with modulated duration, or can be trains of short pulses with modulated numbers of pulses.","The presence, duration and number of these pulses depends on the readings of thermal sensor 207 and the treatment temperature selected by user.","Controller 109 is programmed with a software code to modulate the pulse durations or their number and is programmed to stabilize the temperature of heater 201 at a user-selected level.","A horizontal figure 8-shaped coil 209 with two petals 210 and 211, which can be performed as two round coils connected to each other with opposite polarities, a vertical figure 8-shaped coil 212 with two petals 213 and 214 similar to petals 210 and 211, and an oval shaped coil 215 are each provided to the stimulation unit 200 to provide sequences of electromagnetic pulses in the treatment target area.","Petals 210 and 211 of the horizontal coil 209 carry electric currents in opposite directions—clockwise and counterclockwise and deliver axial magnetic fields to the treatment area in opposite directions: in the body and out of the body.","At the target area in kidney, which is about 5 cm displaced from the plane containing each of the coils, the axial components generated by two coils mutually compensate each other, so the axial magnetic field in the target area is close to zero.","At the same time, the radial components of the magnetic fields created by petals 210 and 211 are of the same direction and add up, creating a substantial magnetic field along the horizontal axis parallel to the plane of coils.","Likewise, petals 213 and 214 of the vertical coil 212 deliver magnetic field along a vertical axis parallel to the plane of coils.","Coil 215 delivers axial magnetic field in the direction normal to the plane of coils.","The system of three coils 209, 212 and 215 are, therefore, able to provide sequential pulsed magnetic fields along all three spatial directions X, Y, Z.","Note that the system of three coils can be rotated from the depicted orientation, while maintaining their respective orientations with one another, without departing from the scope of the invention.","For protection of electronic controller and the coils 209, 212 and 215 from high voltage spikes arising at the end of electromagnetic pulses, all three coils are connected in parallel with free wheel diodes 216, 217 and 218.These free wheel diodes can be secured on the belt applicator 102 or can be a part of the controller 109 or contained within the controller housing.","All coils and the heater are held together by flexible glue, preferably silicone RTV rubber, not shown.","Certain alterative heaters configurations that can be used in TA-PEMF stimulation unit 200 are shown in FIGS.","3a and 3b.","In FIG.","3a, the carbon fiber heater is made of a meandering CF strip 301 attached to the belt applicator (not shown).","The ends of the CF strip 302 and 303 are connected to the power output of controller 209 to supply the power necessary for heating.","This heater comprises a long CF strip, so it has a higher resistance than heater 201, consumes less current and can be used for delivering long pulses.","FIG.","3b shows an inductive heater 305 powered by a high frequency generator.","The inductive heater 305 can be used for deep heating of kidneys and comprises a coil, which can be independent or be one of PEMF coils (e.g.","coil 211).","In this embodiment, the controller 109 via a switch 306 intermittently connects coil 211 to high frequency generator 307, thus providing deep heating of the target area or to PEMF circuit delivering electromagnetic stimulation.","Based on readings of the thermal sensor on the belt applicator and the treatment temperature selected by the user, the controller 109 selectively controls the power outputs to provide stabilization of temperature at a desired level.","FIG.","4 shows another implementation of the stimulating unit for treatment of CKD, which employs only a set of PEMF stimulation coils and does not include a heater.","This embodiment of the apparatus consumes significantly less energy than the previous embodiments.","The tradeoff is between a long treatment and a short treatment accelerated by heat stimulation.","With average consumption of energy under 10 Watts and lithium batteries, this embodiment of the treatment device can work for several hours without recharging and can provide effective and efficient treatment.","In addition, thermal stimulation can be provided by independent devices for deep heating, like ultrasound or high frequency diathermia devices.","Or, induction of heat shock proteins (HSP) in a kidney can be achieved by the whole body thermal stimulation in a bathtub, sauna or steam room.","Three 10-30 minute sessions a week allows maintaining an elevated concentration of HSPs in kidneys.","PEMF and heat stimulation can be separated in time and still be efficient and efficacious.","Even without heat stimulation, the disclosed method of treatment of CKD can be successfully employed for treatment of CKD using long (3-4 hours) daily treatment sessions.","A portable, battery powered PEMF device with “daisy” resembling coils in the stimulator makes this strategy easy and efficient.","The process of PEMF stimulation of kidney is schematically illustrated in FIGS.","5a, 5b and 5c, wherein coils, kidney, magnetic and electric fields are depicted in a rectangular system of coordinates XYZ.","Three coils, such as previously described, are sequentially energized by the controller.","The directions of respective electrical currents are shown in FIGS.","5a-5c by arrows.","Coil 209 with two horizontal petals 210 and 211 delivers a pulsed magnetic field B, lines of which are parallel to the ZX plane and normal to Y axis.","This magnetic field induces electric field E, lines of which are parallel to the YZ plane and normal to X axis.","The electric field E lines are locked on themselves and are induced in the whole area around the coils, including the kidney and surrounding tissues.","For simplicity in FIGS.","5a-5c, they are shown only in the kidney.","Coils 212 and 215 deliver electric field E in planes normal to the Y and Z axes, correspondently.","The disclosed system of electromagnetic coils is positioned in one plane but is configured to deliver three-dimensional electromagnetic stimulation (3-D PEMF).","This novel arrangement of electromagnetic coils generally resembles a flower, such as a daisy.","The “daisy” stimulator provides every cell in a treatment zone with sequential stimulation by electric fields in each of the three directions: Ex, Ey and Ez.","The stimulating electric field E is a vector.","This fact and the consequences of the vector nature of the stimulating field have not been previously appreciated in the art.","FIGS.","6a, 6b and 7 schematically illustrate the importance of this feature.","Further discussion herein will be conducted with the assumption that the electric pulses applied to a cell are of appropriate amplitude and duration for activation of Ata receptors.","This means that the applied electric pulses are about or higher than 1 mV/cm in amplitude and their duration is significantly longer than a time of cell relaxation, which is about 1 microsecond.","In contrast, the durations conventionally used in the art are mainly in the range of 25-1000 microseconds.","At the beginning of each pulse, a transient period lasting about 1 microsecond takes place.","During this period, the mobile ions inside the electrically conductive cytoplasm and the intercellular space outside the cell are redistributed in such a way that the electric field inside the cytoplasm is zero.","After the transient period, the cell stays under stationary (static) distribution of the electric field during the rest of the pulse.","This redistribution of the ions leads to significant change of electric fields in the membrane.","The maximums of electric field Em are located in the parts of membrane that is normal to the applied field and close to zero minimums where the membrane surface is parallel to external field E. The electric field Em in the membrane is defined by the ratio of the cell size to the thickness of membrane and is about 1000 times of the external electric field, comprising approximately 1000 mV/cm.","Because the actual electric field in membrane depends on the size of the cell, larger cells are more susceptive to the electric stimulation than smaller ones.","For example, the linear size of macrophages is about 2.5 times the size of neutrophils, which means that activation of A2a receptors on macrophages is easier to achieve.","And this is good news, because the major damage to kidney in CKD is done by the relatively large macrophage cells.","The process of interaction of adenosine receptors with the electric field is illustrated in FIGS.","6a and 6b.","FIG.","6a represents a cell without electric field.","For simplicity, only several receptors are shown; in reality, hundreds to thousands of A2a receptors are imbedded in a membrane of one cell.","Numeral 601 designates cytosol, the inside volume of the cell separated from the intercellular space by a lipid membrane 602, the thickness of which is exaggerated for clarity of explanation.","Numerals 603 and 604 designate adenosine A2a receptors, which are in the inactive state and are unable to bind with adenosine ligands and transduce biological signals into the cell.","Adenosine ligands are depicted in FIGS.","6a and 6b as AD; they are present around the cell in significant concentration and are available for binding with active A2a receptors.","Numeral 605 is an active A2a receptor bound to adenosine ligand.","FIG.","6b represents the same cell in electrical field E. In the membrane, maximal electric field Em is applied to receptors 603 and 604.This electric field is about 1000 times higher than applied field E and is capable of switching A2a receptors from the inactive to the active state (from OFF to ON).","The voltage sensor that switches cellular receptors is a two-position switch.","It includes a charged group of atoms capable of moving from one position to another under action of electric field.","Only one direction of the electric field parallel to the axis of its sensitivity can affect the position of the electric switch (voltage sensor) of the receptor and turn it ON.","The opposite direction of the electric field can only push the charged group of atoms in the OFF position, where it already is, so no switching occurs.","Assuming that the direction of switching ON is from inside the cell to outside, the switched ON receptor will be 604.Relocation of the charged group of atoms in the receptor protein molecule causes its conformational change and makes the receptor capable of binding with adenosine ligands.","Thus, receptor 604 becomes active, promptly binds with adenosine ligand AD from outside the cell and becomes a bound receptor that transduces the biological signal into the cell and farther along the adenosine signaling pathway.","As experimental data on PEMF activation of A2a receptors suggests, the total amount of A2a receptors activated by a one-dimensional electric field is approximately equal to the number of active receptors without electric stimulation.","Thus, a one-dimensional electric stimulation causes a two-fold increase of adenosine active receptors, while three-dimensional stimulation causes a four-fold increase of active receptors or doubles the increase of the one-dimensional electric stimulation.","FIG.","7 schematically illustrates applications of stimulating Ex, Ey and Ez electric fields.","An electric field applied along one axis, for example X, practically does not affect the electric field and receptors located in the plane normal to the applied field, YZ plane.","The same is true for the other two axis, Y and Z.","The receptors located in planes XZ and XY, respectively, are not sensitive to normal electric fields.","As shown in FIG.","7, sequential stimulation along each of axis X, Y and Z adds three new groups of activated receptors and leads to a four-fold increase of total numbers of active A2a receptors on a cell.","These receptors additionally activated by stimulation and ligand bound A2a receptors are relatively stable; they disassociate with ligands and return to a basal state around 2 hours after the end of stimulation.","For simplicity in this disclosure, only unipolar electric pulses are discussed.","However, stimulating pulses of the opposite polarity can be used as well.","In such case, the pulsed electric field is applied in one direction for a period of time long enough to activate receptors and have them bind to the ligands; then the pulsed electric field of opposite direction is applied for the same period of time and the cycle is repeated.","The electric field of the opposite direction cannot switch off the activating switch in a receptor that is already bound to a ligand, so activated and bound to ligands receptors will be accumulated on both ends of the stimulated cell along the direction of electric field.","The period of stimulation time in one direction can be about 5 to 15 minutes.","Bipolar stimulation will activate even more A2a receptors and provide even stronger adenosine anti-inflammation and immune-suppressive signaling.","For this bipolar embodiment, a simple circuit for reversing electric currents in coils is added to the apparatus.","These types of reversing circuits are well known to those skilled in the art.","In a preferred embodiment of the invention, controller 109 provides DC pulses sequentially, one pulse at a time, to coils 209, 212 and 215, thereby creating electric fields along axes X, Y, Z.","It is contemplated though, that pulses may be provided to two or three coils simultaneously with different relative amplitudes and polarities.","This type of stimulation is more complicated, but allows for producing electric fields in any direction across the cell and can achieve the highest possible activation rate of the receptors A2a.","A2a adenosine receptors under applied electric field experience a conformational change that makes them able to bind with adenosine ligands.","In an A2a protein molecule there is an electric field sensor comprising a charged group of atoms that operates as a switch creating this conformational transition.","Whatever the nature of the electric field sensor is, under influence of electric field E, a charged group of atoms (ion) of the sensor is moving with a velocity Vi defined by the equation: Vi=μE (1) Here constant μ is mobility of the ion.","During a stimulating electric pulse, the ion will travel distance ΔL equal to the product of velocity Vi and duration τp: ΔL=Vi τp=μEτp=μ(Eτp) (2) Thus, every stimulating pulse shifts the electric switch of a receptor on a distance ΔL equal to mobility of the ion μ multiplied by Eτp—the product of electric field and pulse duration.","Value Eτp sometimes is called “electric impulse”.","After accumulating multiple shifts, the switch relocates from the OFF position into the ON position and stays there.","From the equation for ΔL, an important scaling law can be inferred: two different pulses produce the same stimulating effect if the product of their amplitudes and durations are the same.","This scaling law, which was not appreciated in the previous art, is significant.","It gives additional understanding and freedom in selecting durations and amplitudes of PEMF systems.","In accordance with specific requirements of his system a designer can select higher electric field amplitudes in combination with shorter durations, or lower amplitudes with longer durations in wide range of values, and still have the same efficiency, provided their electric impulses are equal: Eτp=constant (3) Operation of the PEMF system will now be described.","For simplicity, only one stimulating unit 200 will be described.","The two stimulating two units (one for each kidney) can be connected to each other in parallel or in series, so their operations are essentially are identical.","The applicator belt 102 is positioned on the back of the patient around his/her waist.","An operator turns on the system by push-button 111.Controller 109 starts generating DC electric pulses energizing in sequence stimulators 103 and 104.The pulses preferably are short, in tens to hundreds of microseconds, so the current through the coils never reaches the maximum that corresponds to the DC voltage.","Exponentially growing currents in coils 209, 212 and 215 creates time varying magnetic fields that induce electric fields in the treatment area.","Induced electric fields are circular; their lines are locked on themselves and lie in vertical or horizontal planes as shown in FIGS.","5a, 5b and 5c.","All coils of the apparatus have a respective free wheel diode connected in parallel to each coil.","During a pulse, when a coil is connected to the DC power supply, a significant amount of energy delivered by the power supply is spent creating a magnetic field around the coil.","At the end of a pulse, when the coil is cut off from the DC pulse, the magnetic energy induces an electric current in the circuit made by the coil and the companion free wheel diode connected in parallel to the coil.","This redirection of magnetic energy into a coil-diode loop protects the circuits from high voltage spikes created by current interruptions in the coil.","PEMF stimulation is performed at a constant or variable repetition rate in the range of 5 to 100 Hz.","With this rate, the heat deposit in coils is low, in the range of several Watts.","It is not sufficient for successful thermal stimulation of the treatment area.","Adequate thermal stimulation is achieved by using additional heater 201 placed adjacent to the treatment area and secured together with electromagnetic coils in one stimulating unit 200.Temperature sensor 207 is placed on heater 201 to avoid overheating and to achieve better control of the treatment zone temperature.","Controller 109 provides power to the heater 201 by delivering DC pulses with the same frequency (repetition rate) as the PEMF stimulation but, depending on the readings of temperature sensors, pulses with different durations.","Actual power delivered to the heaters 201 is controlled by the duration of the pulses.","When the temperature reading reaches the value higher or lower than predetermined by the controller, the pulse duration is shortened to allow the applicator to cool down or prolonged to heat it up and keep the temperature stable.","The physiological feeling of comfortable warmth in the back may be used as an indication that the temperature is right and should not be increased or decreased.","The temperature desired for successful thermal stimulation is about 42-43 degrees Celsius at the patient's skin.","In another implementation of invention a sequence of short pulses is supplied by controller 109 to the heater 201 with numbers of heating pulses modulated by the temperature reading and a desired temperature setting.","FIG.","8 illustrates voltage (a), current and magnetic field (b), electric field (c) and thermal pulses (d and e) used in certain embodiments of the apparatus and kidney treatment method.","When a DC step voltage V0 is applied to an inductive coil of the stimulator, the electric current I and the magnetic field B generated by it grow exponentially.","At the beginning of a pulse, magnetic field B increases practically linearly (b).","So, stimulating field E, which follows B as a derivative function, is almost constant (c).","The DC pulse is interrupted by controller 109 with duration of pulse τp being 5-10 times shorter than the time of relaxation of the inductive circuit τ=L/R, where the inductance of the coil is L and its resistance R. In one embodiment of the present invention, the duration of DC pulses applied to the treatment coils is in the range of 5 μs to 100 μs.","In another embodiment, the duration of pulses is in the range of 50 μs to 200 μs.","In yet another embodiment, duration of pulses can be as high as 1000 μs.","The maximum magnetic field Bmax in the treatment zone in one embodiment is in the range of 0.5 mT to 1.0 mT.","In another embodiment Bmax is in the range of 1.0 to 10.0 mT.","The maximum electric current through coils is 100-500 A.","The pulsing frequency (repetition rate) f used for PEMF stimulation and temperature control is in the range of 5 to 100 Hz.","In any case, whatever the Bmax and duration of the pulse τp is, the electric field E in the treatment zone should preferably stay in the range of 0.1 mV/cm to 20 mV/cm.","A higher amplitude E with a shorter pulse duration τp or lower amplitude with longer pulse duration can be used, but their product Eτp, in accordance with the scaling law should be not less than a minimum value of about 100 μsmV/cm.","In the wide range of electrical field amplitudes E and durations τp described above, there is a rule for selection of the right combination of the amplitude and duration: 1000 μsmV/cm>=E τp>=100 μsmV/cm.","Repetition rate fin the range of 5 Hz to 100 Hz produces the same biological effects and its choice is not significant for stimulation.","FIG.","8 graph d) illustrates voltage pulses sent by controller 109 to heater 201.The duration of pulses τh is modulated for stabilization of temperature at a desired level.","In the case where a high frequency is used for heating of treatment zone, pulse τh depicts the heating power generated by HF generator.","FIG.","8 graph e) illustrates sequence of heating pulses when they are short and modulation of applied heat is done by changing their numbers.","In one example of treatment regimen for chronic kidney disease, separate sessions of deep heating with ultrasound or HF hypothermia heater or hot bath or sauna 3 to 4 times a week combined with PEMF treatment 3 to 7 times a week can be utilized.","While the invention has been described in connection with what is presently considered to be the most practical and preferred example embodiments, it will be apparent to those of ordinary skill in the art that the invention is not to be limited to the disclosed example embodiments.","It will be readily apparent to those of ordinary skill in the art that many modifications and equivalent arrangements can be made thereof without departing from the spirit and scope of the present disclosure, such scope to be accorded the broadest interpretation of the appended claims so as to encompass all equivalent structures and products.","It is also within the scope of the invention to combine features, functions, advantages and aspects of the various embodiments described herein.","Thus, the embodiments of the invention may comprise combinations of aspects of any one or more of these exemplary embodiments.","For purposes of interpreting the claims for the present invention, it is expressly intended that the provisions of Section 112, sixth paragraph of 35 U.S.C.","are not to be invoked unless the specific terms “means for” or “step for” are recited in a claim."]],"string":"[\n [\n \"METHODS AND APPARATUS FOR TREATMENT OF CHRONIC KIDNEY DISEASE\",\n \"A method and apparatus for treatment of chronic kidney disease (CKD), particular diabetic nephropathy, are disclosed.\",\n \"The method comprises activation of adenosine A2a receptors in parenchymal and immune cells infiltrated into kidneys.\",\n \"The activation is performed by PEMF (pulsed electromagnetic field) stimulation applied locally to kidneys.\",\n \"Adenosine A2a signaling pathway is a potent anti-inflammatory and immuno-suppressive regulator that has been proven to attenuate inflammation and injury in diabetic nephropathy.\",\n \"Efficient activation of A2a receptors is achieved by applying electromagnetic field stimulation consecutively in 3 spatial dimensions.\",\n \"This allows attaining a significant increase in activation of A2a receptors in comparison with one-dimensional stimulation.\",\n \"Assistant thermal stimulation may be applied to increase expression of heat shock proteins (HSPs) in parenchymal cells.\",\n \"HSPs improve protein functions, protect cells from apoptosis and necrosis, increase metabolism, and symbiotically enhance effects of electric stimulation on CKD.\"\n ],\n [\n \"1.A method of treating chronic kidney disease of a mammal, the method comprising: increasing a concentration of Ata adenosine receptors on cellular membranes in a kidney of the mammal by: delivering a first pulsed magnetic field with a first polarity to a kidney of the mammal along a first orthogonal direction; delivering a second pulsed magnetic field with the first polarity to the kidney of the mammal along a second orthogonal, the second orthogonal direction being perpendicular to the first orthogonal direction, the first and second orthogonal directions being in a common plane; and delivering a third pulsed magnetic field with the first polarity to the kidney of the mammal along a third orthogonal direction, the third orthogonal direction being perpendicular to the common plane.\",\n \"2.The method of claim 1, further comprising delivering each of the first pulsed magnetic field, the second pulsed magnetic field and the third pulsed magnetic field to the kidney of the mammal in a second polarity that is the opposite of the first polarity.\",\n \"3.The method of claim 1, further comprising: applying a pulsed electromagnetic field (PEMF) treatment session to the kidney of the mammal on at least three days during a seven day period, wherein each PEMF treatment session includes the steps of delivering the first pulsed magnetic field, the second pulsed magnetic field and the third pulsed magnetic field to the kidney of the mammal for a duration of two to four hours; and applying an independent whole body heat stimulation to the mammal two to four times during the seven day period to induce heat shock proteins in the kidney of the mammal.\",\n \"4.The method of claim 1, further comprising heating the kidney of the mammal by energizing a high frequency generator.\",\n \"5.The method of claim 1, further comprising generating a first electrical current in a first coil such that the first electrical current flows in a clockwise rotational direction in a first petal of the first coil and the first electrical current flows in a counter-clockwise rotational direction in a second petal of the first coil.\",\n \"6.The method of claim 5, further comprising generating a second electrical current in a second coil such that the second electrical current flows in a clockwise rotational direction in a first petal of the second coil and the second electrical current flows in a counter-clockwise rotational direction in a second petal of the second coil.\",\n \"7.The method of claim 1, further comprising energizing a plurality of coils at a frequency of 1-1000 Hz to generate an electrical field that delivers the first pulsed magnetic field, the second pulsed magnetic field and the third pulsed magnetic field.\",\n \"8.The method of claim 1, further comprising energizing a plurality of coils with an electrical impulse of not less 100 μsmV/cm to deliver the first pulsed magnetic field, the second pulsed magnetic field and the third pulsed magnetic field.\",\n \"9.The method of claim 1, further comprising: delivering the first pulsed magnetic field via a first coil; delivering the second pulsed magnetic field via a second coil; delivering the third pulsed magnetic field via a third coil; and arranging the first, second and third coils in a common plane.\",\n \"10.The method of claim 9, further comprising arranging the first and second coils within a perimeter loop of the third coil.\",\n \"11.The method of claim 10, further comprising forming each of the first and second coils to resemble a FIG.\",\n \"8.12.The method of claim 9, further comprising forming each of the first and second coils to resemble a FIG.\",\n \"8.13.The method of claim 1, further comprising providing heat input to the mammal sufficient to maintain a body surface temperature measurement in a range of 40-43 degree Celsius.\",\n \"14.A method of treating chronic kidney disease of a mammal, the method comprising: delivering by a first coil a first pulsed magnetic field to a kidney of the mammal; delivering by a second coil a second pulsed magnetic field to the kidney of the mammal; and delivering by a third coil a third pulsed magnetic field to the kidney of the mammal; and arranging the first, second and third coils in a common plane.\",\n \"15.The method of claim 14, further comprising arranging the first and second coils within a perimeter loop of the third coil.\",\n \"16.The method of claim 14, further comprising configuring each of the first and second coils to resemble a FIG.\",\n \"8.17.The method of claim 14, further comprising applying a treatment session to the kidney of the mammal on at least three days during a seven day period, wherein each treatment session includes the steps of delivering the first pulsed magnetic field, the second pulsed magnetic field and the third pulsed magnetic field to the kidney of the mammal for a duration of two to four hours.\",\n \"18.The method of claim 14, further comprising applying a treatment session to the kidney of the mammal on at least three days during a seven day period, wherein each treatment session includes applying heat input to the mammal sufficient to maintain a body surface temperature measurement in a range of 40-43 degree Celsius.\",\n \"19.A method of treating chronic kidney disease of a mammal, the method comprising: increasing a concentration of Ata adenosine receptors on cellular membranes in a kidney of the mammal by: applying a pulsed electromagnetic field (PEMF) treatment session to the kidney of the mammal on at least three days during a seven day period, wherein each PEMF treatment session includes the steps of delivering a first pulsed magnetic field, a second pulsed magnetic field and a third pulsed magnetic field to the kidney of the mammal for a duration of two to four hours; and applying an independent whole body heat stimulation to the mammal two to four times during the seven day period to induce heat shock proteins in the kidney of the mammal, wherein the first pulsed magnetic field is delivered via a first coil, wherein the second pulsed magnetic field is delivered via a second coil, wherein the third pulsed magnetic field is delivered via a third coil, and wherein each of the first, second and third coils are arranged in a common plane.\",\n \"20.The method of claim 19, further comprising: arranging the first and second coils within a perimeter loop of the third coil; and orienting the second coil along an orthogonal axis that is ninety degrees offset from an orthogonal axis of the first coil.\"\n ],\n [\n \" BACKGROUND Kidneys are bean-shaped organs that serve as a biological filter removing metabolic waste from blood to the urinary bladder.\",\n \"The basic structural and functional unit of kidney is a nephron, the main function of which is to regulate the concentration of water and soluble substances in blood, reabsorbing the vital elements and excreting the rest as urine.\",\n \"In humans, a normal kidney contains 800,000 to 1.5 million nephrons.\",\n \"The adequate kidney function is imperative for survival: kidneys control level of electrolytes in blood, regulate blood volume, blood pressure and blood pH.\",\n \"Bacterial infections, accumulation of toxic materials and auto-immune diseases may cause inflammatory disease of kidneys, also called nephritis.\",\n \"The symptoms of nephritis are a rise in blood pressure, back pain, edema and fatigue.\",\n \"Albumin and other serum proteins in increasing quantities pass into urine, creating a condition called proteinuria.\",\n \"If the condition continues to deteriorate, uremia or renal failure develops.\",\n \"Renal failure leads to accumulation of high concentrations of metabolic waste in the blood and eventually causes death.\",\n \"The conventional medical treatment is the removal of this waste by filtering blood with a dialysis machine, also called an artificial kidney.\",\n \"When the condition deteriorates still further, transplantation of a kidney is the last and the only option.\",\n \"Chronic kidney disease has several underlying reasons and involves the glomeruli, tubules or interstitial tissue surrounding the glomeruli and tubules.\",\n \"The glomerulus is a network (tuft) of capillaries that performs the first step of blood filtration.\",\n \"The renal tubule is the part of nephron containing the fluid filtered through the glomerulus.\",\n \"Glomerulonephritis (GN) is inflammation of glomeruli.\",\n \"GN may lead to serious kidney damage and, in some patients, kidney failure.\",\n \"The causes of glomerulonephritis are complex and diverse, some have a genetic basis and others are associated with systemic diseases.\",\n \"While treatment is available for some types of GN, many traditional therapies are toxic, non-specific and have the potential for major side effects.\",\n \"Some GN subtypes do not respond to any therapies.\",\n \"Worldwide, GN is the most common single cause of end-stage renal disease (ESRD).\",\n \"There are more than 20 million Americans with chronic kidney disease and 50,000 of them die annually.\",\n \"Though chronic autoimmune disorders such as systemic lupus erythematosus affect a significant percentage of the human population and strongly diminish the quality of life and life expectancy, the molecular mechanisms of those diseases are still poorly understood, hindering the development of novel treatment strategies.\",\n \"Autoimmune diseases are caused by disturbed recognition of foreign and self-antigens, leading to the emergence of auto-reactive T-cells (so-called immunization phase).\",\n \"T-cells are a major regulator of the inflammatory cascade.\",\n \"The auto-reactive T-cells then trigger the second (so-called effector) phase of the disease which is characterized by activation of the immune cells that cause immune-mediated damage to host tissues.\",\n \"For a long time, neutrophils have been neglected as potential players in the development of autoimmune diseases.\",\n \"However, a significant amount of new experimental data suggests that neutrophils play an important role in both the immunization and the effector phase of autoimmune diseases.\",\n \"Taken together, neutrophils should be considered as one of the most important cell types in autoimmune diseases and a suitable target for treatment of those diseases.\",\n \"Neutrophils are the most common type of white blood cell in human body and are the first line of attack against invaders.\",\n \"In a person with a healthy immune system, the white blood cells gather at an infected or injured site in the body and produce chemical substances that help fight off the infection.\",\n \"These substances increase inflammatory reaction and attack invaders, causing some collateral injury to healthy tissue.\",\n \"Usually the immune system is capable of producing additional substances that make the inflammatory process self-contained and limited in time.\",\n \"Inflammation in a healthy individual usually signals that the immune system is responding appropriately to harmful invaders, damaged cells, irritants, or injury.\",\n \"But, in case of autoimmune diseases, due to faulty interactions between blood and other immune system cells, the inflammation increases.\",\n \"Attracted by cytokines (messenger molecules) expressed by activated endothelium and other residential cells in inflamed tissues, neutrophils, using “roll”, “stop” and “exit” mechanism leave blood vessels and congregate at a focus of infection.\",\n \"Migrated into the kidney, neutrophils release their own cytokines, which in turn activate several other cell types and amplify inflammatory response.\",\n \"In addition to recruiting and activating other cells of the immune system, neutrophils play a key role in the front-line defense against invading pathogens.\",\n \"Neutrophils have three methods for directly attacking micro-organisms: phagocytosis, release of soluble anti-microbials substances, and generation of neutrophil extracellular traps (NETs).\",\n \"NETs are networks of extracellular fibers, primarily composed of DNA from neutrophils, which bind and kill extracellular pathogens while minimizing damage to the host cells.\",\n \"NETs may also have a deleterious effect on the host.\",\n \"It is believed that excessive expression of extracellular histone complexes from DNA combined with their slow clearing plays an important role in the development of autoimmune kidney diseases, particular in lupus.\",\n \"There is a need in developing of novel therapies that inhibit recruitment of neutrophils from blood vessels and deactivate neutrophils that already aggregated in kidneys.\",\n \"The autoimmune diseases cause significant numbers of patients that progress to ESRD.\",\n \"But the most important disease responsible for the highest number of patients with ESRD is diabetic nephropathy.\",\n \"The growing epidemic of obesity-related insulin resistance and the difficulties in managing diabetes have made diabetic nephropathy the major single cause of kidney disease in the developed world.\",\n \"Despite current clinical interventions involving tight glycemic and blood pressure control, diabetic nephropathy progresses in most patients with a significant proportion reaching end-stage renal failure.\",\n \"In addition, the development of diabetic nephropathy exacerbates cardiovascular disease, which leads to increased morbidity and mortality.\",\n \"Given the limited renal protection with current treatments, it is critical that alternative therapeutic approaches are developed to protect diabetic patients from diabetic kidney disease.\",\n \"Recent studies have identified macrophage-mediated injury as an important component in the development of diabetic nephropathy that is not addressed by current therapies.\",\n \"Further evidence has shown that macrophages are the major immune cells infiltrating the kidney in type 1 and type 2 diabetes, and that they contribute to the development of renal injury.\",\n \"In view of this new evidence, diabetic nephropathy has been reclassified as a chronic inflammatory disease which is triggered and maintained by metabolic disturbances of diabetes mellitus.\",\n \"Elements of the diabetic milieu activate the vascular endothelium, inducing increased expression of cell adhesion molecules (ICAM-1/VCAM-1) that adhere to circulating blood monocytes.\",\n \"Using the “roll”, “stop” and “exit” sequence the blood monocytes migrate from the blood vessels to the kidney, where they differentiate into macrophages.\",\n \"Glomerular podocytes, mesangial cells and tubular epithelial cells are also stimulated by the diabetic milieu.\",\n \"They additionally secrete chemokines (MCP-1/OPN) that facilitate transendothelial and intrarenal monocytes/macrophage migration.\",\n \"Also, the diabetic renal parenchymal cells produce colony stimulating factor-1 (CSF-1) which induces local proliferation of macrophages that also contributes to the accumulation of macrophages in diabetic kidneys.\",\n \"Activated macrophages release reactive oxygen species and pro-inflammatory cytokines, which cause injury to podocytes, interstitial and tubular cells.\",\n \"These macrophages also can secrete profibrotic cytokines that induce mesangial and fibroblast proliferation and development of fibrosis.\",\n \"This ongoing renal injury and fibrosis promotes the progression of diabetic nephropathy.\",\n \"Renal interstitial fibrosis (RIF) is the common pathological process of chronic kidney diseases leading inevitably to renal function deterioration.\",\n \"RIF and preceding epithelial-mesenchymal transition (EMT) are commonly triggered in diabetic kidney by an early occurring renal inflammation.\",\n \"However, an effective approach to prevent EMT and RIF is still lacking.\",\n \"Adenosine A2a receptor recently emerged as a potent inflammation regulator.\",\n \"Adenosine activation of A2a receptors suppresses the EMT process and protects kidneys against RIF.\",\n \"Experimental studies suggest that activation of A2a significantly suppresses the deposition of collagen types I and III thus inhibiting the EMT progress.\",\n \"As a result, activation of A2a effectively alleviates EMT and RIF, suggesting A2a receptors as a potential therapeutic target for treatment of RIF.\",\n \"Development of therapeutic strategies for treatment of macrophage-mediated injury in kidney that selectively target mechanisms of macrophage recruitment, proliferation and activation seems to be an attractive choice in comparison with general immunosuppression.\",\n \"Now it is commonly accepted that macrophages play a critical role in the development of diabetic nephropathy.\",\n \"Current therapies, however, are unable to prevent the progressive renal damage caused by these inflammatory cells.\",\n \"There is an urgent need for novel anti-inflammation and immuno-suppressive therapies aimed at reducing macrophage recruitment, accumulation and activation in diabetic kidneys.\",\n \"Adenosine is a purine nucleoside generated by metabolically stressed or inflamed tissues that is recognized as a major endogenous anti-inflammatory regulator.\",\n \"Under normal conditions, adenosine is continuously released from cells as a product of ATP degradation.\",\n \"Adenosine concentration in extracellular space is controlled by an enzyme called adenosine deaminase (ADA) which breaks it down and keeps the concentration level in low-micromolar to high-nanomolar range.\",\n \"However, during conditions of stress, such as hypoxia during inflammation, levels of extracellular adenosine rise dramatically (up to 200-fold).\",\n \"This is partly due to increased production of AMP in hypoxic conditions, but substantial amounts of adenosine are also produced by the sequential dephosphorylation of adenine nucleotides released from platelets and hematopoietic cells, as well as damaged cells.\",\n \"Adenosine regulates the function of the innate and adaptive immune systems through targeting virtually every cell type that is involved in orchestrating the immune/inflammatory response.\",\n \"Of the four adenosine receptors (A1, A2a, A1b, A3), A2a receptors have taken center stage as the primary anti-inflammatory effectors of extracellular adenosine.\",\n \"This broad, anti-inflammatory effect of A2a receptor activation is a result of the predominant expression of A2a receptors on monocytes/macrophages, dendritic cells, mast cells, neutrophils, endothelial cells, eosinophils, epithelial cells, as well as lymphocytes, NK cells, and NKT cells.\",\n \"A2a receptors play a critical role in controlling leukocyte trafficking by suppressing release of cytokines that induce production of adhesion molecules (ICAM-1/VCAM-1) and promote the “roll”, “stop” and “exit” mechanism bringing neutrophils and monocytes/macrophages from blood vessels into tissues.\",\n \"A2a receptor activation inhibits early and late events occurring during an immune response, which include immune cell trafficking, immune cell proliferation, proinflammatory cytokine production, and cytotoxicity.\",\n \"In late stage of inflammation in addition to limiting inflammation, A2a receptors participate in tissue remodeling and restoration.\",\n \"Consistent with their multifaceted, immunoregulatory action on immune cells, A2a receptors have been shown to impact the course of a wide spectrum of ischemic, autoimmune, infectious, and allergic diseases.\",\n \"A2a receptors are found in all parenchymal cells in kidney: glomerular endothelium, podocytes, tubular endothelium and mesangial cells.\",\n \"Adenosine A2a receptor activation was recently shown to be renoprotective in diabetic nephropathy.\",\n \"Activated A2a receptors protect kidneys from diabetic nephropathy through actions on hematopoietic and kidney-derived cells.\",\n \"Podocytes contribute to the maintenance of the glomerular filtration barrier and abnormalities of podocyte structure and function lead to a number of glomerular diseases.\",\n \"Activation of adenosine A2a receptors preserves the structure and function of podocytes and leads to a reduction of proteinuria and preservation of glomerular function.\",\n \"Macrophages play a critical role in immune response against pathogenic invaders.\",\n \"Beyond increasing inflammation and stimulating the immune system, macrophages also play an important anti-inflammatory role and can decrease immune reactions through the release of cytokines.\",\n \"Macrophages that encourage inflammation are called M1 macrophages, whereas those that decrease inflammation and encourage tissue repair are called M2 macrophages.\",\n \"This difference is reflected in their metabolism, where macrophages have the unique ability to metabolize one amino acid, arginine, to either a “killer” molecule (nitric oxide) or a “repair” molecule (ornithine).\",\n \"Macrophages morph in phenotypes M1 or M2 depending on the environment in which they are activated.\",\n \"In the presence of cytokines such as IL-12 and IL-23 from T helper-1 cells that orchestrate initial stage of immune response, the “classically” activated macrophages are pro-inflammatory M1 type, whereas at the final stage of inflammation in presence of cytokine IL-10 and TGF-β from T helper-2 cells, macrophages become “alternatively” activated into anti-inflammation type M2, that promote tissue restoration.\",\n \"The same macrophage that was a pro-inflammatory M1 type at the beginning of inflammation can be re-activated into an anti-inflammatory M2 type at the final stage of the inflammation.\",\n \"Consistent with its generally restorative function in tissues, A2a receptor activation has been repeatedly shown to have effects that prevent excessive classical macrophage activation thereby resulting in tissue protection.\",\n \"In contrast to the suppressive effect of adenosine on the production of proinflammatory mediators, adenosine augments production of anti-inflammatory cytokine IL-10 that promotes activation of macrophages into M2 type.\",\n \"Thus, in addition to deactivating classically activated macrophages, A2a receptor signaling changes macrophage metabolism and enables switching their phenotype to alternative type M2 that participates in tissue restoration.\",\n \"The protective effect of stimulation of A2a receptors was proven to correlate with decreased expression of adhesion molecules (ICAM-1/VCAM-1) and reduction of transmigration of neutrophil and monocytes/macrophages into the kidney.\",\n \"In addition, the renal microvasculature responds to A2a receptors stimulation by vasodilation that results in increased blood flow in the renal microcirculation and contributes to the renal protection.\",\n \"Pulsed Electromagnetic Field Therapy (PEMF) is a new non-invasive method of treatment of numerous medical conditions related to injuries and inflammations of different tissues: bones, cartilages, soft and neurological tissues.\",\n \"For centuries it was a common knowledge that the natural wound healing involves generation of endogenous electric fields.\",\n \"Recently it has been discovered that the endogenous electric fields control also the processes of remodeling and healing bones and cartilages.\",\n \"In PEMF therapy the electric field is carried into the treatment zone by a pulsed magnetic field produced by electromagnetic coils from outside the body.\",\n \"A PEMF system applies a series of magnetic pulses to injured tissue where each magnetic pulse induces an electrical signal that stimulates cellular anti-inflammatory and anabolic activities.\",\n \"PEMF therapy reduces pain associated with inflammation by suppressing production of pain mediator prostaglandin E2 and accelerates natural healing of tissues.\",\n \"Multiple studies have demonstrated effectiveness and safety of PEMF therapy in suppressing inflammation.\",\n \"Recently it has been established by Varani et al.\",\n \"that the anti-inflammation mechanism of action of PEMF on a cell is due to its ability to increase the concentration of receptors A2a on the cell membrane.\",\n \"PEMF stimulation increases the number of active A2a receptors on the cell membrane by creating a conformational change of their protein and making them active and available for binding with adenosine ligand.\",\n \"The signal to the cell and the biological response of the cell's machinery depends on both the concentration of ligands in extracellular space and the concentration of receptors on the cell membrane.\",\n \"In other words, the magnitude of biological response of the cell depends on the product of these two concentrations.\",\n \"As a result, the same response can be achieved by two different ways: by changing concentration of adenosine around the cell or by changing concentration of the receptors on the cell membrane.\",\n \"The essence of the discovery of Varani et al.\",\n \"is that the adenosine signaling pathway can be up-regulated without changing extracellular adenosine concentration.\",\n \"It can be achieved by PEMF stimulation alone.\",\n \"According to the experimental data, the A2a receptors can be up-regulated by the pulsed electric fields with amplitude above 50 μV/cm.\",\n \"In the environment rich in extracellular adenosine, which is always the case with inflamed or stressed tissues, the up-regulation of A2a receptors leads to significant amplification of adenosine signaling.\",\n \"PEMF stimulation triggers the same physiological response of the cell as an increase in concentration of adenosine or another A2a agonist in the extracellular space.\",\n \"In either case, the magnitude of signal from A2a receptors to the cellular machinery increases as well as the downstream effects of the A2a signaling.\",\n \"PEMF stimulation can affect a wide variety of cells that express A2a receptors, including T cells, macrophages, neutrophils and other lymphocytes.\",\n \"All parenchymal kidney cells carry A2a receptors and can be stimulated by PEMF.\",\n \"A2a receptors stimulated by PEMF are able to inhibit multiple processes occurring during an immune response, including immune cell trafficking and proliferation, pro-inflammatory cytokine production and cytotoxicity.\",\n \"In addition to limiting inflammation, A2a receptors participate in tissue remodeling and repair.\",\n \"A2a receptors have been shown to impact the course of autoimmune, infectious, and allergic diseases.\",\n \"PEMF stimulation of A2a receptors generates immunosuppressive action by inhibiting overreactive immune cells, thereby protecting tissues from collateral inflammatory damage.\",\n \"PEMF stimulation of A2a receptors provides a novel regulatory tool for immune/inflammatory diseases of various organs, including kidney.\",\n \"They can be a critical part of the physiological negative feedback that limits local inflammatory responses.\",\n \"Increased by PEMF stimulation, A2a signaling inhibits development of cytotoxicity and cytokine-producing activity in T-cells.\",\n \"Stimulated by PEMF A2a receptors in autoreactive T-cells generate strong immunosuppressive action that reduces chronic inflammation and subsequent damage to the affected organ.\",\n \"Upregulation of adenosine A2a signaling by PEMF in hematopoietic and renal parenchymal cells results in cascades of actions.\",\n \"It can down-regulate recruitment of inflammatory leucocytes from blood vessels by acting on the vascular epithelial cell and disrupting the “roll”, “stop” and “exit” mechanism.\",\n \"Via A2a receptors signaling PEMF promotes changing phenotypes of macrophages from pro-inflammatory type M1 to anti-inflammatory type M2, stimulates resolution of inflammation and tissue restoration.\",\n \"It promotes improvement of function of podocytes, reduction of proteinuria, and down-regulation of expression of pro-inflammatory cytokines in mesangial cells—the major source of inflammation in diabetic kidney.\",\n \"Also it inhibits renal interstitial fibrosis (RIF) by suppressing the epithelial-mesenchymal transition (EMT).\",\n \"These outstanding anti-inflammation and immuno-suppressive actions of A2a receptors attracted attention of many researchers as a potential basis for development of new drugs for treatment of various inflammatory diseases.\",\n \"Unfortunately, free adenosine has a very short half-life time in plasma, about 10 seconds, which severely limits its usage as a systemic drug.\",\n \"However, a number of agonists with high selectivity to A2a receptors and long half-life in plasma have been developed recently, keeping the hope of developing these drugs alive.\",\n \"It should be noticed that all new knowledge recently accumulated about A2a effects on the inflamed tissues came mainly from in vitro experiments and animal trials.\",\n \"Unfortunately, in human clinical trials, a big problem with adenosine agonists has been encountered—a strong hemodynamic effect.\",\n \"A2a receptors are abundantly expressed in vascular endothelium and play a significant role in regulating blood flow throughout the body.\",\n \"Systemic activation of A2a receptors leads to vasodilation in the whole vascular bed and increases blood flow, which, in turn, creates a significant reactive drop in blood pressure, increase in heart rate and cardiac index.\",\n \"These hemodynamic side effects limit systemic dosing of A2a agonists to the level at which they are no longer effective at resolution of inflammation.\",\n \"This problem has contributed to the failure of several A2a agonists.\",\n \"Examples of discontinued A2a agonists trials include GW328267X from GlaxoSmithKline PLC and UK-432097 from Pfizer Inc. Several A2a agonists, though, are still in clinical trials for inflammation-related indications.\",\n \"The anti-inflammation and immuno-suppressive actions of A2a receptors can be employed by using PEMF stimulation of the affected areas.\",\n \"For more than thirty years of experimental and clinical use of PEMF stimulation for different tissues there were no noticed side effects.\",\n \"PEMF stimulation boosts activity of A2a receptors locally; it does not increase the concentration of adenosine around the cells, but instead, increases A2a concentration on the cellular membranes.\",\n \"Local PEMF stimulation effects inflamed tissues only, where the concentration of adenosine is high, up to 200-fold of the base line.\",\n \"As has been mentioned before, under normal physiological conditions concentration of adenosine in tissues is low and PEMF stimulation effects are minimal.\",\n \"This is the major reason why PEMF therapy does not have side effects.\",\n \"Stress response is one of the most important biological reactions to a wide variety of unfavorable physiological and environmental conditions.\",\n \"It is a part of cell's own repair system that is evolutionary conserved and universally expressed from bacteria to humans.\",\n \"One of the first cellular reactions on stress is rapid generation of so called heat shock proteins (HSPs).\",\n \"Heat-shock proteins play numerous roles in cell function, including modulating protein activity by changing protein conformation, promoting multi-protein complex assembly/disassembly, regulating protein degradation within the proteasome pathway, facilitating protein translocation across organelle membranes, and ensuring proper folding of nascent polypeptide chains during protein translation.\",\n \"When cells are overstressed, the common response is to undergo cell death by one of two pathways, either ‘necrosis’ or ‘apoptosis’.\",\n \"Recently, both routes to cell death have been revealed to share similar mechanisms, with heat shock proteins and their cofactors responsible for inhibiting both apoptotic and necrotic pathways.\",\n \"So, the effective biological function of HSPs is to preserve cell survival by maintaining the vital functions of proteins.\",\n \"In practical terms, HSPs can be induced by local thermal stimulation with temperatures 40-43 degrees C. for 10-30 minutes.\",\n \"Deep thermal stimulation can be achieved by ultrasound, high radiofrequency and microwave diathermia devices.\",\n \"Also, kidneys can be stimulated as a part of the whole body thermal stimulation in a hot bath, sauna and steam room.\",\n \"After thermal stimulation, intracellular concentration of HSPs rapidly grows to several fold level at 24 hours and returns to the basal level after 48-72 hours.\",\n \"Intracellular buildup of HSPs is triggered by activation of Heat Shock Factor (HSF), whereas HSP concentration is controlled by enzyme adenosine deaminase (ADA) that degrades HSPs.\",\n \"Luckily, the activity of ADA is inhibited by PEMF stimulation, so, as a result, PEMF helps to keep the HSPs concentration high.\",\n \"It is known from animal studies that HSP72 inhibits proliferation and apoptosis in tubular cells and diminishes accumulation of fibroblasts and collagen in renal parenchyma, thus slowing the process of fibrosis.\",\n \"It was also observed that HSP70 exerts strong cytoprotection of mesangial cells from oxidative injury in experiments with ischemic reperfusion.\",\n \"Overall, a significant body of evidence suggests that HSPs delay the progression of chronic kidney disease (CKD) by the anti-apoptotic activity and cytoprotection.\",\n \"Koga et al.\",\n \"in the article “Mild electrical stimulation and heat shock ameliorates progressive proteinuria and renal inflammation in mouse model of Alport syndrome” demonstrated that combination of electrical and heat stimulation provides anti-proteinuric and anti-inflammatory effects on Alport mice through multiple signaling pathways via podocytic activation of Akt (protein kinase B) and induction of HSP72.The authors suggest a new therapeutic strategy to decelerate the progression of Alport syndrome by applying combined electrical and heat stimulation.\",\n \"In the experiment described in the article, the electrical stimulation was provided by a pulsed direct electric current applied to the experimental animals via electrodes attached to the skin.\",\n \"The thermal stimulation was delivered from the same electrodes.\",\n \"In U.S. Pat.\",\n \"No.\",\n \"6,941,172 B2, issued to Zvi Nachum, a “Method and device for restoring kidney function using electromagnetic stimulation” is disclosed.\",\n \"The method of restoring kidney function includes the steps of: (a) providing a device including: a conducting coil, and a signal generator for providing a plurality of electrical impulses to the coil; (b) disposing the conducting coil proximate to a kidney of a patient, and (c) delivering the electrical impulses conducted to the conducting coil, so as to produce an electromagnetic field, the electromagnetic field acting so as to stimulate the kidney.\",\n \"The inventor states that this method is applicable only to the cases of acute kidney failure, mainly for traumatic ones, not to CKD: “The device and method of the present invention appear to be most effective in treating kidney failure due to trauma.\",\n \"Kidney failure due to trauma is acute, and is generally reversible, at least during the initial stages.\",\n \"Without wishing to be limited by theory, it is believed that a static charge builds up within the tissues of the kidney, for reasons that are not yet fully understood.\",\n \"This static charge inhibits proper functioning of the kidney.\",\n \"As long as no significant irreversible damage has been caused to the kidney, the kidney can be stimulated into regaining normal performance by clearing the static charge within the tissues of the kidney by application of an electromagnetic field using the device and method of the present invention”.\",\n \"It should be mentioned that it is widely accepted in the art that the biologically active component of electromagnetic stimulation is the electric field produced by the changing magnetic field.\",\n \"In the Nachum patent mentioned above, there is no disclosure of the magnitude of the electric field applied to the kidney.\",\n \"But from the time dependency of the magnetic field which is described in the patent, it can be easy estimated that the electric field was about 1 μV/cm or less.\",\n \"This level of electric field is, probably, enough to change the pathologic charging in the kidney caused by trauma, but it is not enough to up-regulate the A2a receptors on kidney cells.\",\n \"In other words, the disclosed Nachum method, developed for restoration of kidney function of a traumatized kidney, cannot be effective in preservation of kidney function deteriorating due to chronic inflammation of kidney.\",\n \"In particular, Nachum makes an explicit “distinction between acute and chronic renal failure is of cardinal importance” as explained in Column 1 starting at line 19 of his patent.\",\n \"Chronic kidney disease and acute renal failure are clearly two different diseases.\",\n \"Therefore, there continues to be a need for devices and methods for treating chronic kidney diseases.\"\n ],\n [\n \" SUMMARY The present invention effectively addresses certain drawbacks in the prior art kidney disease treatment devices and methods.\",\n \"One object of certain embodiments is to provide PEMF stimulation for reduction of kidney inflammation and suppression of excessive immune response.\",\n \"Another objective of certain embodiments is reduction of proteinuria, deceleration of progression of chronic kidney disease and preservation of kidney function.\",\n \"Another objective of certain embodiments is to treat autoimmune diseases of kidneys.\",\n \"Yet another objective of certain embodiments is to treat diabetic nephropathy.\",\n \"Another objective of certain embodiments is to apply highly efficient PEMF stimulation to activate A2a receptors of parenchymal kidney cells and the immune cells accumulated in kidneys: T-cells, macrophages and neutrophils.\",\n \"An objective of certain embodiments is to provide thermal stimulation to kidneys to increase vitality of kidney cells by induction of Heat Shock Proteins including HSP72 that inhibit apoptosis and necrosis of kidney cells.\",\n \"Another objective of certain embodiments is to provide for treatment of kidneys a portable self-administered system that combines PEMF with thermal stimulations, which does not interfere with everyday activity and that can be used in office, home or in a car.\",\n \"The aforementioned objectives can be achieved by providing a Thermally Assisted Pulse Electromagnetic Field (TA-PEMF) stimulation system that delivers both thermal and electric stimulation to kidneys.\",\n \"The thermal stimulation is delivered by heating elements made of carbon fiber (CF) fabric secured to a belt that placed on the patient's back adjacent to kidneys.\",\n \"The electric stimulation with enhanced efficiency is provided by three PEMF coils on each kidney, one is made as a flat spiral coil (Tesla coil) and two others are shaped in number 8 shape, one horizontal and one vertical.\",\n \"Three coils and the heating element comprise a stimulation element that is secured to the belt adjacent to kidney.\",\n \"The heating elements, controlled independently from PEMF coils, provide temperature at the surface of the body in the range of 40-43 degree C. that induces HSPs in kidneys.\",\n \"The electrical stimulation, generated by PEMF coils, delivers rectangular electric pulses to kidneys with amplitudes, durations and frequencies that activate A2a receptors on both kidney-derived and immune cells.\",\n \"The disclosure includes a method and apparatus for treatment of chronic kidney disease (CKD), particular diabetic nephropathy.\",\n \"The method can include activation of adenosine A2a receptors in parenchymal and immune cells infiltrated into kidneys.\",\n \"The activation is performed by PEMF (pulsed electromagnetic field) stimulation applied locally to kidneys.\",\n \"Adenosine A2a signaling pathway is a potent anti-inflammatory and immuno-suppressive regulator that has been proven to attenuate inflammation and injury in diabetic nephropathy.\",\n \"Efficient activation of A2a receptors is achieved by applying electromagnetic field stimulation consecutively in 3 spatial dimensions.\",\n \"This allows attaining a significant increase in activation of A2a receptors in comparison with one-dimensional stimulation.\",\n \"Assistant thermal stimulation may be applied to increase expression of heat shock proteins (HSPs) in parenchymal cells.\",\n \"HSPs improve protein functions, protect cells from apoptosis and necrosis, increase metabolism, and symbiotically enhance effects of electric stimulation on CKD.\",\n \"The disclosure includes a pulsed electromagnetic field therapy stimulation system for delivering treatment to a patient with chronic kidney disease.\",\n \"The system includes an applicator and a first stimulation unit disposed in the applicator and located such that the first stimulation unit is disposed over a first kidney of the patient when the applicator is worn by the patient.\",\n \"The first stimulation unit comprises a plurality of coils.\",\n \"A first coil comprises a first petal and a second petal, the second petal extending longitudinally opposite the first petal along a first longitudinal axis, and defining a first coil crossover point where the first and second petals intersect.\",\n \"A second coil comprises a first petal and a second petal, the second petal extending longitudinally opposite the first petal along a second longitudinal axis, and defining a second coil crossover point where the first and second petals intersect.\",\n \"A third coil comprises a perimeter loop.\",\n \"The first coil, second coil and third coil are disposed in a plane.\",\n \"The first longitudinal axis is axially rotated ninety degrees with respect to the second longitudinal axis.\",\n \"The first coil crossover point and second coil crossover point coincide.\",\n \"The first coil and the second coil are disposed within the perimeter loop of the third coil.\",\n \"The disclosure further includes a pulsed electromagnetic field therapy stimulator for treatment of chronic kidney disease in a patient.\",\n \"The stimulator is coupled to a controller and a power source.\",\n \"The controller is configured to selectively generate an electrical current to one or more coils.\",\n \"The stimulator includes a first coil oriented along a first orthogonal axis.\",\n \"The first coil comprises a first petal and a second petal.\",\n \"The second petal extends longitudinally opposite the first petal such that an electrical current in the first petal flows in a first rotational direction and the electrical current in the second petal flows in a second rotational direction, wherein the second direction being opposite of the first direction.\",\n \"The stimulator also includes a second coil oriented along a second orthogonal axis ninety degrees offset from the first orthogonal axis.\",\n \"The second coil comprises a first petal and a second petal.\",\n \"The second petal extends longitudinally opposite the first petal such that an electrical current in the first petal flows in a first rotational direction and the electrical current in the second petal flows in a second rotational direction, wherein the second direction being opposite of the first direction.\",\n \"The first orthogonal axis and the second orthogonal axis lie in a common plane.\",\n \"A third coil can also be provided.\",\n \"The third coil comprises a loop disposed in the common plane and surrounds the first coil and the second coil.\",\n \"The disclosure additionally includes a method of treating chronic kidney disease of a mammal.\",\n \"The method includes increasing a concentration of Ata adenosine receptors on cellular membranes in a kidney of the mammal by delivering a first pulsed magnetic field with a first polarity to the kidney of the mammal along a first orthogonal direction.\",\n \"A second pulsed magnetic field with the first polarity is delivered to the kidney of the mammal along a second orthogonal direction.\",\n \"The second orthogonal direction is perpendicular to the first orthogonal direction.\",\n \"The first and second orthogonal directions are also in a common plane.\",\n \"A third pulsed magnetic field with the first polarity is further delivered to the kidney of the mammal along a third orthogonal direction.\",\n \"The third orthogonal direction is perpendicular to the common plane.\",\n \"The detailed technology and preferred embodiments implemented for the subject invention are described in the following paragraphs accompanying the appended drawings for people skilled in this field to well appreciate the features of the claimed invention.\",\n \"It is understood that the features mentioned hereinbefore and those to be commented on hereinafter may be used not only in the specified combinations, but also in other combinations or in isolation, without departing from the scope of the present invention.\"\n ],\n [\n \"PRIORITY This application is a divisional of U.S. patent application Ser.\",\n \"No.\",\n \"14/822,577, filed Aug. 10, 2015, which claims the priority benefit of U.S.\",\n \"Provisional Patent Application Ser.\",\n \"No.\",\n \"61/999,921, filed Aug. 11, 2014, and both of which are hereby incorporated herein by reference in their entirety.\",\n \"FIELD The invention relates to treatment of kidney disease.\",\n \"More particularly, the invention relates to methods and apparatus for treating chronic kidney disease utilizing pulsed electromagnetic fields.\",\n \"BACKGROUND Kidneys are bean-shaped organs that serve as a biological filter removing metabolic waste from blood to the urinary bladder.\",\n \"The basic structural and functional unit of kidney is a nephron, the main function of which is to regulate the concentration of water and soluble substances in blood, reabsorbing the vital elements and excreting the rest as urine.\",\n \"In humans, a normal kidney contains 800,000 to 1.5 million nephrons.\",\n \"The adequate kidney function is imperative for survival: kidneys control level of electrolytes in blood, regulate blood volume, blood pressure and blood pH.\",\n \"Bacterial infections, accumulation of toxic materials and auto-immune diseases may cause inflammatory disease of kidneys, also called nephritis.\",\n \"The symptoms of nephritis are a rise in blood pressure, back pain, edema and fatigue.\",\n \"Albumin and other serum proteins in increasing quantities pass into urine, creating a condition called proteinuria.\",\n \"If the condition continues to deteriorate, uremia or renal failure develops.\",\n \"Renal failure leads to accumulation of high concentrations of metabolic waste in the blood and eventually causes death.\",\n \"The conventional medical treatment is the removal of this waste by filtering blood with a dialysis machine, also called an artificial kidney.\",\n \"When the condition deteriorates still further, transplantation of a kidney is the last and the only option.\",\n \"Chronic kidney disease has several underlying reasons and involves the glomeruli, tubules or interstitial tissue surrounding the glomeruli and tubules.\",\n \"The glomerulus is a network (tuft) of capillaries that performs the first step of blood filtration.\",\n \"The renal tubule is the part of nephron containing the fluid filtered through the glomerulus.\",\n \"Glomerulonephritis (GN) is inflammation of glomeruli.\",\n \"GN may lead to serious kidney damage and, in some patients, kidney failure.\",\n \"The causes of glomerulonephritis are complex and diverse, some have a genetic basis and others are associated with systemic diseases.\",\n \"While treatment is available for some types of GN, many traditional therapies are toxic, non-specific and have the potential for major side effects.\",\n \"Some GN subtypes do not respond to any therapies.\",\n \"Worldwide, GN is the most common single cause of end-stage renal disease (ESRD).\",\n \"There are more than 20 million Americans with chronic kidney disease and 50,000 of them die annually.\",\n \"Though chronic autoimmune disorders such as systemic lupus erythematosus affect a significant percentage of the human population and strongly diminish the quality of life and life expectancy, the molecular mechanisms of those diseases are still poorly understood, hindering the development of novel treatment strategies.\",\n \"Autoimmune diseases are caused by disturbed recognition of foreign and self-antigens, leading to the emergence of auto-reactive T-cells (so-called immunization phase).\",\n \"T-cells are a major regulator of the inflammatory cascade.\",\n \"The auto-reactive T-cells then trigger the second (so-called effector) phase of the disease which is characterized by activation of the immune cells that cause immune-mediated damage to host tissues.\",\n \"For a long time, neutrophils have been neglected as potential players in the development of autoimmune diseases.\",\n \"However, a significant amount of new experimental data suggests that neutrophils play an important role in both the immunization and the effector phase of autoimmune diseases.\",\n \"Taken together, neutrophils should be considered as one of the most important cell types in autoimmune diseases and a suitable target for treatment of those diseases.\",\n \"Neutrophils are the most common type of white blood cell in human body and are the first line of attack against invaders.\",\n \"In a person with a healthy immune system, the white blood cells gather at an infected or injured site in the body and produce chemical substances that help fight off the infection.\",\n \"These substances increase inflammatory reaction and attack invaders, causing some collateral injury to healthy tissue.\",\n \"Usually the immune system is capable of producing additional substances that make the inflammatory process self-contained and limited in time.\",\n \"Inflammation in a healthy individual usually signals that the immune system is responding appropriately to harmful invaders, damaged cells, irritants, or injury.\",\n \"But, in case of autoimmune diseases, due to faulty interactions between blood and other immune system cells, the inflammation increases.\",\n \"Attracted by cytokines (messenger molecules) expressed by activated endothelium and other residential cells in inflamed tissues, neutrophils, using “roll”, “stop” and “exit” mechanism leave blood vessels and congregate at a focus of infection.\",\n \"Migrated into the kidney, neutrophils release their own cytokines, which in turn activate several other cell types and amplify inflammatory response.\",\n \"In addition to recruiting and activating other cells of the immune system, neutrophils play a key role in the front-line defense against invading pathogens.\",\n \"Neutrophils have three methods for directly attacking micro-organisms: phagocytosis, release of soluble anti-microbials substances, and generation of neutrophil extracellular traps (NETs).\",\n \"NETs are networks of extracellular fibers, primarily composed of DNA from neutrophils, which bind and kill extracellular pathogens while minimizing damage to the host cells.\",\n \"NETs may also have a deleterious effect on the host.\",\n \"It is believed that excessive expression of extracellular histone complexes from DNA combined with their slow clearing plays an important role in the development of autoimmune kidney diseases, particular in lupus.\",\n \"There is a need in developing of novel therapies that inhibit recruitment of neutrophils from blood vessels and deactivate neutrophils that already aggregated in kidneys.\",\n \"The autoimmune diseases cause significant numbers of patients that progress to ESRD.\",\n \"But the most important disease responsible for the highest number of patients with ESRD is diabetic nephropathy.\",\n \"The growing epidemic of obesity-related insulin resistance and the difficulties in managing diabetes have made diabetic nephropathy the major single cause of kidney disease in the developed world.\",\n \"Despite current clinical interventions involving tight glycemic and blood pressure control, diabetic nephropathy progresses in most patients with a significant proportion reaching end-stage renal failure.\",\n \"In addition, the development of diabetic nephropathy exacerbates cardiovascular disease, which leads to increased morbidity and mortality.\",\n \"Given the limited renal protection with current treatments, it is critical that alternative therapeutic approaches are developed to protect diabetic patients from diabetic kidney disease.\",\n \"Recent studies have identified macrophage-mediated injury as an important component in the development of diabetic nephropathy that is not addressed by current therapies.\",\n \"Further evidence has shown that macrophages are the major immune cells infiltrating the kidney in type 1 and type 2 diabetes, and that they contribute to the development of renal injury.\",\n \"In view of this new evidence, diabetic nephropathy has been reclassified as a chronic inflammatory disease which is triggered and maintained by metabolic disturbances of diabetes mellitus.\",\n \"Elements of the diabetic milieu activate the vascular endothelium, inducing increased expression of cell adhesion molecules (ICAM-1/VCAM-1) that adhere to circulating blood monocytes.\",\n \"Using the “roll”, “stop” and “exit” sequence the blood monocytes migrate from the blood vessels to the kidney, where they differentiate into macrophages.\",\n \"Glomerular podocytes, mesangial cells and tubular epithelial cells are also stimulated by the diabetic milieu.\",\n \"They additionally secrete chemokines (MCP-1/OPN) that facilitate transendothelial and intrarenal monocytes/macrophage migration.\",\n \"Also, the diabetic renal parenchymal cells produce colony stimulating factor-1 (CSF-1) which induces local proliferation of macrophages that also contributes to the accumulation of macrophages in diabetic kidneys.\",\n \"Activated macrophages release reactive oxygen species and pro-inflammatory cytokines, which cause injury to podocytes, interstitial and tubular cells.\",\n \"These macrophages also can secrete profibrotic cytokines that induce mesangial and fibroblast proliferation and development of fibrosis.\",\n \"This ongoing renal injury and fibrosis promotes the progression of diabetic nephropathy.\",\n \"Renal interstitial fibrosis (RIF) is the common pathological process of chronic kidney diseases leading inevitably to renal function deterioration.\",\n \"RIF and preceding epithelial-mesenchymal transition (EMT) are commonly triggered in diabetic kidney by an early occurring renal inflammation.\",\n \"However, an effective approach to prevent EMT and RIF is still lacking.\",\n \"Adenosine A2a receptor recently emerged as a potent inflammation regulator.\",\n \"Adenosine activation of A2a receptors suppresses the EMT process and protects kidneys against RIF.\",\n \"Experimental studies suggest that activation of A2a significantly suppresses the deposition of collagen types I and III thus inhibiting the EMT progress.\",\n \"As a result, activation of A2a effectively alleviates EMT and RIF, suggesting A2a receptors as a potential therapeutic target for treatment of RIF.\",\n \"Development of therapeutic strategies for treatment of macrophage-mediated injury in kidney that selectively target mechanisms of macrophage recruitment, proliferation and activation seems to be an attractive choice in comparison with general immunosuppression.\",\n \"Now it is commonly accepted that macrophages play a critical role in the development of diabetic nephropathy.\",\n \"Current therapies, however, are unable to prevent the progressive renal damage caused by these inflammatory cells.\",\n \"There is an urgent need for novel anti-inflammation and immuno-suppressive therapies aimed at reducing macrophage recruitment, accumulation and activation in diabetic kidneys.\",\n \"Adenosine is a purine nucleoside generated by metabolically stressed or inflamed tissues that is recognized as a major endogenous anti-inflammatory regulator.\",\n \"Under normal conditions, adenosine is continuously released from cells as a product of ATP degradation.\",\n \"Adenosine concentration in extracellular space is controlled by an enzyme called adenosine deaminase (ADA) which breaks it down and keeps the concentration level in low-micromolar to high-nanomolar range.\",\n \"However, during conditions of stress, such as hypoxia during inflammation, levels of extracellular adenosine rise dramatically (up to 200-fold).\",\n \"This is partly due to increased production of AMP in hypoxic conditions, but substantial amounts of adenosine are also produced by the sequential dephosphorylation of adenine nucleotides released from platelets and hematopoietic cells, as well as damaged cells.\",\n \"Adenosine regulates the function of the innate and adaptive immune systems through targeting virtually every cell type that is involved in orchestrating the immune/inflammatory response.\",\n \"Of the four adenosine receptors (A1, A2a, A1b, A3), A2a receptors have taken center stage as the primary anti-inflammatory effectors of extracellular adenosine.\",\n \"This broad, anti-inflammatory effect of A2a receptor activation is a result of the predominant expression of A2a receptors on monocytes/macrophages, dendritic cells, mast cells, neutrophils, endothelial cells, eosinophils, epithelial cells, as well as lymphocytes, NK cells, and NKT cells.\",\n \"A2a receptors play a critical role in controlling leukocyte trafficking by suppressing release of cytokines that induce production of adhesion molecules (ICAM-1/VCAM-1) and promote the “roll”, “stop” and “exit” mechanism bringing neutrophils and monocytes/macrophages from blood vessels into tissues.\",\n \"A2a receptor activation inhibits early and late events occurring during an immune response, which include immune cell trafficking, immune cell proliferation, proinflammatory cytokine production, and cytotoxicity.\",\n \"In late stage of inflammation in addition to limiting inflammation, A2a receptors participate in tissue remodeling and restoration.\",\n \"Consistent with their multifaceted, immunoregulatory action on immune cells, A2a receptors have been shown to impact the course of a wide spectrum of ischemic, autoimmune, infectious, and allergic diseases.\",\n \"A2a receptors are found in all parenchymal cells in kidney: glomerular endothelium, podocytes, tubular endothelium and mesangial cells.\",\n \"Adenosine A2a receptor activation was recently shown to be renoprotective in diabetic nephropathy.\",\n \"Activated A2a receptors protect kidneys from diabetic nephropathy through actions on hematopoietic and kidney-derived cells.\",\n \"Podocytes contribute to the maintenance of the glomerular filtration barrier and abnormalities of podocyte structure and function lead to a number of glomerular diseases.\",\n \"Activation of adenosine A2a receptors preserves the structure and function of podocytes and leads to a reduction of proteinuria and preservation of glomerular function.\",\n \"Macrophages play a critical role in immune response against pathogenic invaders.\",\n \"Beyond increasing inflammation and stimulating the immune system, macrophages also play an important anti-inflammatory role and can decrease immune reactions through the release of cytokines.\",\n \"Macrophages that encourage inflammation are called M1 macrophages, whereas those that decrease inflammation and encourage tissue repair are called M2 macrophages.\",\n \"This difference is reflected in their metabolism, where macrophages have the unique ability to metabolize one amino acid, arginine, to either a “killer” molecule (nitric oxide) or a “repair” molecule (ornithine).\",\n \"Macrophages morph in phenotypes M1 or M2 depending on the environment in which they are activated.\",\n \"In the presence of cytokines such as IL-12 and IL-23 from T helper-1 cells that orchestrate initial stage of immune response, the “classically” activated macrophages are pro-inflammatory M1 type, whereas at the final stage of inflammation in presence of cytokine IL-10 and TGF-β from T helper-2 cells, macrophages become “alternatively” activated into anti-inflammation type M2, that promote tissue restoration.\",\n \"The same macrophage that was a pro-inflammatory M1 type at the beginning of inflammation can be re-activated into an anti-inflammatory M2 type at the final stage of the inflammation.\",\n \"Consistent with its generally restorative function in tissues, A2a receptor activation has been repeatedly shown to have effects that prevent excessive classical macrophage activation thereby resulting in tissue protection.\",\n \"In contrast to the suppressive effect of adenosine on the production of proinflammatory mediators, adenosine augments production of anti-inflammatory cytokine IL-10 that promotes activation of macrophages into M2 type.\",\n \"Thus, in addition to deactivating classically activated macrophages, A2a receptor signaling changes macrophage metabolism and enables switching their phenotype to alternative type M2 that participates in tissue restoration.\",\n \"The protective effect of stimulation of A2a receptors was proven to correlate with decreased expression of adhesion molecules (ICAM-1/VCAM-1) and reduction of transmigration of neutrophil and monocytes/macrophages into the kidney.\",\n \"In addition, the renal microvasculature responds to A2a receptors stimulation by vasodilation that results in increased blood flow in the renal microcirculation and contributes to the renal protection.\",\n \"Pulsed Electromagnetic Field Therapy (PEMF) is a new non-invasive method of treatment of numerous medical conditions related to injuries and inflammations of different tissues: bones, cartilages, soft and neurological tissues.\",\n \"For centuries it was a common knowledge that the natural wound healing involves generation of endogenous electric fields.\",\n \"Recently it has been discovered that the endogenous electric fields control also the processes of remodeling and healing bones and cartilages.\",\n \"In PEMF therapy the electric field is carried into the treatment zone by a pulsed magnetic field produced by electromagnetic coils from outside the body.\",\n \"A PEMF system applies a series of magnetic pulses to injured tissue where each magnetic pulse induces an electrical signal that stimulates cellular anti-inflammatory and anabolic activities.\",\n \"PEMF therapy reduces pain associated with inflammation by suppressing production of pain mediator prostaglandin E2 and accelerates natural healing of tissues.\",\n \"Multiple studies have demonstrated effectiveness and safety of PEMF therapy in suppressing inflammation.\",\n \"Recently it has been established by Varani et al.\",\n \"that the anti-inflammation mechanism of action of PEMF on a cell is due to its ability to increase the concentration of receptors A2a on the cell membrane.\",\n \"PEMF stimulation increases the number of active A2a receptors on the cell membrane by creating a conformational change of their protein and making them active and available for binding with adenosine ligand.\",\n \"The signal to the cell and the biological response of the cell's machinery depends on both the concentration of ligands in extracellular space and the concentration of receptors on the cell membrane.\",\n \"In other words, the magnitude of biological response of the cell depends on the product of these two concentrations.\",\n \"As a result, the same response can be achieved by two different ways: by changing concentration of adenosine around the cell or by changing concentration of the receptors on the cell membrane.\",\n \"The essence of the discovery of Varani et al.\",\n \"is that the adenosine signaling pathway can be up-regulated without changing extracellular adenosine concentration.\",\n \"It can be achieved by PEMF stimulation alone.\",\n \"According to the experimental data, the A2a receptors can be up-regulated by the pulsed electric fields with amplitude above 50 μV/cm.\",\n \"In the environment rich in extracellular adenosine, which is always the case with inflamed or stressed tissues, the up-regulation of A2a receptors leads to significant amplification of adenosine signaling.\",\n \"PEMF stimulation triggers the same physiological response of the cell as an increase in concentration of adenosine or another A2a agonist in the extracellular space.\",\n \"In either case, the magnitude of signal from A2a receptors to the cellular machinery increases as well as the downstream effects of the A2a signaling.\",\n \"PEMF stimulation can affect a wide variety of cells that express A2a receptors, including T cells, macrophages, neutrophils and other lymphocytes.\",\n \"All parenchymal kidney cells carry A2a receptors and can be stimulated by PEMF.\",\n \"A2a receptors stimulated by PEMF are able to inhibit multiple processes occurring during an immune response, including immune cell trafficking and proliferation, pro-inflammatory cytokine production and cytotoxicity.\",\n \"In addition to limiting inflammation, A2a receptors participate in tissue remodeling and repair.\",\n \"A2a receptors have been shown to impact the course of autoimmune, infectious, and allergic diseases.\",\n \"PEMF stimulation of A2a receptors generates immunosuppressive action by inhibiting overreactive immune cells, thereby protecting tissues from collateral inflammatory damage.\",\n \"PEMF stimulation of A2a receptors provides a novel regulatory tool for immune/inflammatory diseases of various organs, including kidney.\",\n \"They can be a critical part of the physiological negative feedback that limits local inflammatory responses.\",\n \"Increased by PEMF stimulation, A2a signaling inhibits development of cytotoxicity and cytokine-producing activity in T-cells.\",\n \"Stimulated by PEMF A2a receptors in autoreactive T-cells generate strong immunosuppressive action that reduces chronic inflammation and subsequent damage to the affected organ.\",\n \"Upregulation of adenosine A2a signaling by PEMF in hematopoietic and renal parenchymal cells results in cascades of actions.\",\n \"It can down-regulate recruitment of inflammatory leucocytes from blood vessels by acting on the vascular epithelial cell and disrupting the “roll”, “stop” and “exit” mechanism.\",\n \"Via A2a receptors signaling PEMF promotes changing phenotypes of macrophages from pro-inflammatory type M1 to anti-inflammatory type M2, stimulates resolution of inflammation and tissue restoration.\",\n \"It promotes improvement of function of podocytes, reduction of proteinuria, and down-regulation of expression of pro-inflammatory cytokines in mesangial cells—the major source of inflammation in diabetic kidney.\",\n \"Also it inhibits renal interstitial fibrosis (RIF) by suppressing the epithelial-mesenchymal transition (EMT).\",\n \"These outstanding anti-inflammation and immuno-suppressive actions of A2a receptors attracted attention of many researchers as a potential basis for development of new drugs for treatment of various inflammatory diseases.\",\n \"Unfortunately, free adenosine has a very short half-life time in plasma, about 10 seconds, which severely limits its usage as a systemic drug.\",\n \"However, a number of agonists with high selectivity to A2a receptors and long half-life in plasma have been developed recently, keeping the hope of developing these drugs alive.\",\n \"It should be noticed that all new knowledge recently accumulated about A2a effects on the inflamed tissues came mainly from in vitro experiments and animal trials.\",\n \"Unfortunately, in human clinical trials, a big problem with adenosine agonists has been encountered—a strong hemodynamic effect.\",\n \"A2a receptors are abundantly expressed in vascular endothelium and play a significant role in regulating blood flow throughout the body.\",\n \"Systemic activation of A2a receptors leads to vasodilation in the whole vascular bed and increases blood flow, which, in turn, creates a significant reactive drop in blood pressure, increase in heart rate and cardiac index.\",\n \"These hemodynamic side effects limit systemic dosing of A2a agonists to the level at which they are no longer effective at resolution of inflammation.\",\n \"This problem has contributed to the failure of several A2a agonists.\",\n \"Examples of discontinued A2a agonists trials include GW328267X from GlaxoSmithKline PLC and UK-432097 from Pfizer Inc. Several A2a agonists, though, are still in clinical trials for inflammation-related indications.\",\n \"The anti-inflammation and immuno-suppressive actions of A2a receptors can be employed by using PEMF stimulation of the affected areas.\",\n \"For more than thirty years of experimental and clinical use of PEMF stimulation for different tissues there were no noticed side effects.\",\n \"PEMF stimulation boosts activity of A2a receptors locally; it does not increase the concentration of adenosine around the cells, but instead, increases A2a concentration on the cellular membranes.\",\n \"Local PEMF stimulation effects inflamed tissues only, where the concentration of adenosine is high, up to 200-fold of the base line.\",\n \"As has been mentioned before, under normal physiological conditions concentration of adenosine in tissues is low and PEMF stimulation effects are minimal.\",\n \"This is the major reason why PEMF therapy does not have side effects.\",\n \"Stress response is one of the most important biological reactions to a wide variety of unfavorable physiological and environmental conditions.\",\n \"It is a part of cell's own repair system that is evolutionary conserved and universally expressed from bacteria to humans.\",\n \"One of the first cellular reactions on stress is rapid generation of so called heat shock proteins (HSPs).\",\n \"Heat-shock proteins play numerous roles in cell function, including modulating protein activity by changing protein conformation, promoting multi-protein complex assembly/disassembly, regulating protein degradation within the proteasome pathway, facilitating protein translocation across organelle membranes, and ensuring proper folding of nascent polypeptide chains during protein translation.\",\n \"When cells are overstressed, the common response is to undergo cell death by one of two pathways, either ‘necrosis’ or ‘apoptosis’.\",\n \"Recently, both routes to cell death have been revealed to share similar mechanisms, with heat shock proteins and their cofactors responsible for inhibiting both apoptotic and necrotic pathways.\",\n \"So, the effective biological function of HSPs is to preserve cell survival by maintaining the vital functions of proteins.\",\n \"In practical terms, HSPs can be induced by local thermal stimulation with temperatures 40-43 degrees C. for 10-30 minutes.\",\n \"Deep thermal stimulation can be achieved by ultrasound, high radiofrequency and microwave diathermia devices.\",\n \"Also, kidneys can be stimulated as a part of the whole body thermal stimulation in a hot bath, sauna and steam room.\",\n \"After thermal stimulation, intracellular concentration of HSPs rapidly grows to several fold level at 24 hours and returns to the basal level after 48-72 hours.\",\n \"Intracellular buildup of HSPs is triggered by activation of Heat Shock Factor (HSF), whereas HSP concentration is controlled by enzyme adenosine deaminase (ADA) that degrades HSPs.\",\n \"Luckily, the activity of ADA is inhibited by PEMF stimulation, so, as a result, PEMF helps to keep the HSPs concentration high.\",\n \"It is known from animal studies that HSP72 inhibits proliferation and apoptosis in tubular cells and diminishes accumulation of fibroblasts and collagen in renal parenchyma, thus slowing the process of fibrosis.\",\n \"It was also observed that HSP70 exerts strong cytoprotection of mesangial cells from oxidative injury in experiments with ischemic reperfusion.\",\n \"Overall, a significant body of evidence suggests that HSPs delay the progression of chronic kidney disease (CKD) by the anti-apoptotic activity and cytoprotection.\",\n \"Koga et al.\",\n \"in the article “Mild electrical stimulation and heat shock ameliorates progressive proteinuria and renal inflammation in mouse model of Alport syndrome” demonstrated that combination of electrical and heat stimulation provides anti-proteinuric and anti-inflammatory effects on Alport mice through multiple signaling pathways via podocytic activation of Akt (protein kinase B) and induction of HSP72.The authors suggest a new therapeutic strategy to decelerate the progression of Alport syndrome by applying combined electrical and heat stimulation.\",\n \"In the experiment described in the article, the electrical stimulation was provided by a pulsed direct electric current applied to the experimental animals via electrodes attached to the skin.\",\n \"The thermal stimulation was delivered from the same electrodes.\",\n \"In U.S. Pat.\",\n \"No.\",\n \"6,941,172 B2, issued to Zvi Nachum, a “Method and device for restoring kidney function using electromagnetic stimulation” is disclosed.\",\n \"The method of restoring kidney function includes the steps of: (a) providing a device including: a conducting coil, and a signal generator for providing a plurality of electrical impulses to the coil; (b) disposing the conducting coil proximate to a kidney of a patient, and (c) delivering the electrical impulses conducted to the conducting coil, so as to produce an electromagnetic field, the electromagnetic field acting so as to stimulate the kidney.\",\n \"The inventor states that this method is applicable only to the cases of acute kidney failure, mainly for traumatic ones, not to CKD: “The device and method of the present invention appear to be most effective in treating kidney failure due to trauma.\",\n \"Kidney failure due to trauma is acute, and is generally reversible, at least during the initial stages.\",\n \"Without wishing to be limited by theory, it is believed that a static charge builds up within the tissues of the kidney, for reasons that are not yet fully understood.\",\n \"This static charge inhibits proper functioning of the kidney.\",\n \"As long as no significant irreversible damage has been caused to the kidney, the kidney can be stimulated into regaining normal performance by clearing the static charge within the tissues of the kidney by application of an electromagnetic field using the device and method of the present invention”.\",\n \"It should be mentioned that it is widely accepted in the art that the biologically active component of electromagnetic stimulation is the electric field produced by the changing magnetic field.\",\n \"In the Nachum patent mentioned above, there is no disclosure of the magnitude of the electric field applied to the kidney.\",\n \"But from the time dependency of the magnetic field which is described in the patent, it can be easy estimated that the electric field was about 1 μV/cm or less.\",\n \"This level of electric field is, probably, enough to change the pathologic charging in the kidney caused by trauma, but it is not enough to up-regulate the A2a receptors on kidney cells.\",\n \"In other words, the disclosed Nachum method, developed for restoration of kidney function of a traumatized kidney, cannot be effective in preservation of kidney function deteriorating due to chronic inflammation of kidney.\",\n \"In particular, Nachum makes an explicit “distinction between acute and chronic renal failure is of cardinal importance” as explained in Column 1 starting at line 19 of his patent.\",\n \"Chronic kidney disease and acute renal failure are clearly two different diseases.\",\n \"Therefore, there continues to be a need for devices and methods for treating chronic kidney diseases.\",\n \"SUMMARY The present invention effectively addresses certain drawbacks in the prior art kidney disease treatment devices and methods.\",\n \"One object of certain embodiments is to provide PEMF stimulation for reduction of kidney inflammation and suppression of excessive immune response.\",\n \"Another objective of certain embodiments is reduction of proteinuria, deceleration of progression of chronic kidney disease and preservation of kidney function.\",\n \"Another objective of certain embodiments is to treat autoimmune diseases of kidneys.\",\n \"Yet another objective of certain embodiments is to treat diabetic nephropathy.\",\n \"Another objective of certain embodiments is to apply highly efficient PEMF stimulation to activate A2a receptors of parenchymal kidney cells and the immune cells accumulated in kidneys: T-cells, macrophages and neutrophils.\",\n \"An objective of certain embodiments is to provide thermal stimulation to kidneys to increase vitality of kidney cells by induction of Heat Shock Proteins including HSP72 that inhibit apoptosis and necrosis of kidney cells.\",\n \"Another objective of certain embodiments is to provide for treatment of kidneys a portable self-administered system that combines PEMF with thermal stimulations, which does not interfere with everyday activity and that can be used in office, home or in a car.\",\n \"The aforementioned objectives can be achieved by providing a Thermally Assisted Pulse Electromagnetic Field (TA-PEMF) stimulation system that delivers both thermal and electric stimulation to kidneys.\",\n \"The thermal stimulation is delivered by heating elements made of carbon fiber (CF) fabric secured to a belt that placed on the patient's back adjacent to kidneys.\",\n \"The electric stimulation with enhanced efficiency is provided by three PEMF coils on each kidney, one is made as a flat spiral coil (Tesla coil) and two others are shaped in number 8 shape, one horizontal and one vertical.\",\n \"Three coils and the heating element comprise a stimulation element that is secured to the belt adjacent to kidney.\",\n \"The heating elements, controlled independently from PEMF coils, provide temperature at the surface of the body in the range of 40-43 degree C. that induces HSPs in kidneys.\",\n \"The electrical stimulation, generated by PEMF coils, delivers rectangular electric pulses to kidneys with amplitudes, durations and frequencies that activate A2a receptors on both kidney-derived and immune cells.\",\n \"The disclosure includes a method and apparatus for treatment of chronic kidney disease (CKD), particular diabetic nephropathy.\",\n \"The method can include activation of adenosine A2a receptors in parenchymal and immune cells infiltrated into kidneys.\",\n \"The activation is performed by PEMF (pulsed electromagnetic field) stimulation applied locally to kidneys.\",\n \"Adenosine A2a signaling pathway is a potent anti-inflammatory and immuno-suppressive regulator that has been proven to attenuate inflammation and injury in diabetic nephropathy.\",\n \"Efficient activation of A2a receptors is achieved by applying electromagnetic field stimulation consecutively in 3 spatial dimensions.\",\n \"This allows attaining a significant increase in activation of A2a receptors in comparison with one-dimensional stimulation.\",\n \"Assistant thermal stimulation may be applied to increase expression of heat shock proteins (HSPs) in parenchymal cells.\",\n \"HSPs improve protein functions, protect cells from apoptosis and necrosis, increase metabolism, and symbiotically enhance effects of electric stimulation on CKD.\",\n \"The disclosure includes a pulsed electromagnetic field therapy stimulation system for delivering treatment to a patient with chronic kidney disease.\",\n \"The system includes an applicator and a first stimulation unit disposed in the applicator and located such that the first stimulation unit is disposed over a first kidney of the patient when the applicator is worn by the patient.\",\n \"The first stimulation unit comprises a plurality of coils.\",\n \"A first coil comprises a first petal and a second petal, the second petal extending longitudinally opposite the first petal along a first longitudinal axis, and defining a first coil crossover point where the first and second petals intersect.\",\n \"A second coil comprises a first petal and a second petal, the second petal extending longitudinally opposite the first petal along a second longitudinal axis, and defining a second coil crossover point where the first and second petals intersect.\",\n \"A third coil comprises a perimeter loop.\",\n \"The first coil, second coil and third coil are disposed in a plane.\",\n \"The first longitudinal axis is axially rotated ninety degrees with respect to the second longitudinal axis.\",\n \"The first coil crossover point and second coil crossover point coincide.\",\n \"The first coil and the second coil are disposed within the perimeter loop of the third coil.\",\n \"The disclosure further includes a pulsed electromagnetic field therapy stimulator for treatment of chronic kidney disease in a patient.\",\n \"The stimulator is coupled to a controller and a power source.\",\n \"The controller is configured to selectively generate an electrical current to one or more coils.\",\n \"The stimulator includes a first coil oriented along a first orthogonal axis.\",\n \"The first coil comprises a first petal and a second petal.\",\n \"The second petal extends longitudinally opposite the first petal such that an electrical current in the first petal flows in a first rotational direction and the electrical current in the second petal flows in a second rotational direction, wherein the second direction being opposite of the first direction.\",\n \"The stimulator also includes a second coil oriented along a second orthogonal axis ninety degrees offset from the first orthogonal axis.\",\n \"The second coil comprises a first petal and a second petal.\",\n \"The second petal extends longitudinally opposite the first petal such that an electrical current in the first petal flows in a first rotational direction and the electrical current in the second petal flows in a second rotational direction, wherein the second direction being opposite of the first direction.\",\n \"The first orthogonal axis and the second orthogonal axis lie in a common plane.\",\n \"A third coil can also be provided.\",\n \"The third coil comprises a loop disposed in the common plane and surrounds the first coil and the second coil.\",\n \"The disclosure additionally includes a method of treating chronic kidney disease of a mammal.\",\n \"The method includes increasing a concentration of Ata adenosine receptors on cellular membranes in a kidney of the mammal by delivering a first pulsed magnetic field with a first polarity to the kidney of the mammal along a first orthogonal direction.\",\n \"A second pulsed magnetic field with the first polarity is delivered to the kidney of the mammal along a second orthogonal direction.\",\n \"The second orthogonal direction is perpendicular to the first orthogonal direction.\",\n \"The first and second orthogonal directions are also in a common plane.\",\n \"A third pulsed magnetic field with the first polarity is further delivered to the kidney of the mammal along a third orthogonal direction.\",\n \"The third orthogonal direction is perpendicular to the common plane.\",\n \"The detailed technology and preferred embodiments implemented for the subject invention are described in the following paragraphs accompanying the appended drawings for people skilled in this field to well appreciate the features of the claimed invention.\",\n \"It is understood that the features mentioned hereinbefore and those to be commented on hereinafter may be used not only in the specified combinations, but also in other combinations or in isolation, without departing from the scope of the present invention.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS FIG.\",\n \"1 is a PEMF system for treatment of a kidney according to an example embodiment.\",\n \"FIG.\",\n \"2 is a schematic of a TA-PEMF stimulation unit according to an example embodiment.\",\n \"FIG.\",\n \"3a is a schematic of a heater for a TA-PEMF stimulation unit according to an example embodiment.\",\n \"FIG.\",\n \"3b is a schematic of another heater for a TA-PEMF stimulation unit according to an example embodiment.\",\n \"FIG.\",\n \"4 is a schematic of a stimulation unit according to an example embodiment.\",\n \"FIGS.\",\n \"5a, 5b and 5c are diagrams of PEMF stimulation of kidney according to an example embodiment.\",\n \"FIG.\",\n \"6a is a diagram of the interaction of adenosine receptors with the electric field due to PEMF stimulation of the kidney according to an example embodiment where the cell is shown without electric field.\",\n \"FIG.\",\n \"6b is a diagram of the interaction of adenosine receptors with the electric field due to PEMF stimulation of the kidney according to an example embodiment where the cell is shown in electrical field E. FIG.\",\n \"7 is a series of diagrams illustrating application of stimulating Ex, Ey and Ez electric fields according to an example embodiment.\",\n \"FIG.\",\n \"8 is a series of diagrams illustrating voltage (a), current and magnetic field (b), electric field (c) and thermal pulses (d and e) used in a PEMP stimulation apparatus according to an example embodiment.\",\n \"While the invention is amenable to various modifications and alternative forms, specifics thereof have been shown by way of example in the drawings and will be described in detail.\",\n \"It should be understood, however, that the intention is not to limit the invention to the particular example embodiments described.\",\n \"On the contrary, the invention is to cover all modifications, equivalents, and alternatives falling within the scope of the invention as defined by the appended claims.\",\n \"DETAILED DESCRIPTION In the following descriptions, the present invention will be explained with reference to various example embodiments; nevertheless, these example embodiments are not intended to limit the present invention to any specific example, embodiment, environment, application, or particular implementation described herein.\",\n \"Therefore, descriptions of these example embodiments are only provided for purpose of illustration rather than to limit the present invention.\",\n \"An embodiment of a method and apparatus for treatment of chronic kidney disease is illustrated by FIG.\",\n \"1.The TA-PEMF stimulation system 100 for treatment of chronic kidney disease is shown with reference to the back 101 side of the patient.\",\n \"An applicator 102 such as a belt attachable to the back of the patient is secured adjacent to the patient and arranged such that a first TA-PEMF stimulation unit 103 is disposed over the left kidney and a second TA-PEMF stimulation unit 104 is disposed over the right kidney.\",\n \"Electrical conduits 105 connect the first and second TA-PEMF stimulation units.\",\n \"The stimulation units 103, 104 can be connected in series, as shown in FIG.\",\n \"1, or in parallel to each other.\",\n \"Additional electrical conduits 106 and 107 connect both stimulating units 103 and 104 to conduit 108 and further to a controller 109.The controller 109 is a computerized control unit, including both a processor and memory, to control the power and operation of the stimulation units disposed in the applicator 102.The controller 109 further includes a display 110, and on/off control button 111 and temperature indicator 112 (e.g.\",\n \"a bar indicator, digital numerical display, sequential LEDs or other similar indication means).\",\n \"Rotation of button 111 allows user to select a desired level of treatment temperature within permissible boundaries.\",\n \"A power cable 113 or conduit connects controller 109 to power supply 114, which can be a battery or DC power supply connected to an AC power outlet.\",\n \"The power supply can also be combined with controller into a single integrated housing.\",\n \"FIG.\",\n \"2 schematically depicts a TA-PEMF stimulation unit 200.A flat resistive heater 201 made of flexible carbon fiber fabric (CF) is provided.\",\n \"Conductive electrodes 203 and 204 are connected to the resistive CF heater 201 and to controller 109 by respective wires 205 and 206.A thermal sensor 207 is secured on heater 201 and is functionally connected to controller 109 by a pair of wires 208.Controller 109 provides DC pulsed power to heater 201.These pulses can be short, long, with modulated duration, or can be trains of short pulses with modulated numbers of pulses.\",\n \"The presence, duration and number of these pulses depends on the readings of thermal sensor 207 and the treatment temperature selected by user.\",\n \"Controller 109 is programmed with a software code to modulate the pulse durations or their number and is programmed to stabilize the temperature of heater 201 at a user-selected level.\",\n \"A horizontal figure 8-shaped coil 209 with two petals 210 and 211, which can be performed as two round coils connected to each other with opposite polarities, a vertical figure 8-shaped coil 212 with two petals 213 and 214 similar to petals 210 and 211, and an oval shaped coil 215 are each provided to the stimulation unit 200 to provide sequences of electromagnetic pulses in the treatment target area.\",\n \"Petals 210 and 211 of the horizontal coil 209 carry electric currents in opposite directions—clockwise and counterclockwise and deliver axial magnetic fields to the treatment area in opposite directions: in the body and out of the body.\",\n \"At the target area in kidney, which is about 5 cm displaced from the plane containing each of the coils, the axial components generated by two coils mutually compensate each other, so the axial magnetic field in the target area is close to zero.\",\n \"At the same time, the radial components of the magnetic fields created by petals 210 and 211 are of the same direction and add up, creating a substantial magnetic field along the horizontal axis parallel to the plane of coils.\",\n \"Likewise, petals 213 and 214 of the vertical coil 212 deliver magnetic field along a vertical axis parallel to the plane of coils.\",\n \"Coil 215 delivers axial magnetic field in the direction normal to the plane of coils.\",\n \"The system of three coils 209, 212 and 215 are, therefore, able to provide sequential pulsed magnetic fields along all three spatial directions X, Y, Z.\",\n \"Note that the system of three coils can be rotated from the depicted orientation, while maintaining their respective orientations with one another, without departing from the scope of the invention.\",\n \"For protection of electronic controller and the coils 209, 212 and 215 from high voltage spikes arising at the end of electromagnetic pulses, all three coils are connected in parallel with free wheel diodes 216, 217 and 218.These free wheel diodes can be secured on the belt applicator 102 or can be a part of the controller 109 or contained within the controller housing.\",\n \"All coils and the heater are held together by flexible glue, preferably silicone RTV rubber, not shown.\",\n \"Certain alterative heaters configurations that can be used in TA-PEMF stimulation unit 200 are shown in FIGS.\",\n \"3a and 3b.\",\n \"In FIG.\",\n \"3a, the carbon fiber heater is made of a meandering CF strip 301 attached to the belt applicator (not shown).\",\n \"The ends of the CF strip 302 and 303 are connected to the power output of controller 209 to supply the power necessary for heating.\",\n \"This heater comprises a long CF strip, so it has a higher resistance than heater 201, consumes less current and can be used for delivering long pulses.\",\n \"FIG.\",\n \"3b shows an inductive heater 305 powered by a high frequency generator.\",\n \"The inductive heater 305 can be used for deep heating of kidneys and comprises a coil, which can be independent or be one of PEMF coils (e.g.\",\n \"coil 211).\",\n \"In this embodiment, the controller 109 via a switch 306 intermittently connects coil 211 to high frequency generator 307, thus providing deep heating of the target area or to PEMF circuit delivering electromagnetic stimulation.\",\n \"Based on readings of the thermal sensor on the belt applicator and the treatment temperature selected by the user, the controller 109 selectively controls the power outputs to provide stabilization of temperature at a desired level.\",\n \"FIG.\",\n \"4 shows another implementation of the stimulating unit for treatment of CKD, which employs only a set of PEMF stimulation coils and does not include a heater.\",\n \"This embodiment of the apparatus consumes significantly less energy than the previous embodiments.\",\n \"The tradeoff is between a long treatment and a short treatment accelerated by heat stimulation.\",\n \"With average consumption of energy under 10 Watts and lithium batteries, this embodiment of the treatment device can work for several hours without recharging and can provide effective and efficient treatment.\",\n \"In addition, thermal stimulation can be provided by independent devices for deep heating, like ultrasound or high frequency diathermia devices.\",\n \"Or, induction of heat shock proteins (HSP) in a kidney can be achieved by the whole body thermal stimulation in a bathtub, sauna or steam room.\",\n \"Three 10-30 minute sessions a week allows maintaining an elevated concentration of HSPs in kidneys.\",\n \"PEMF and heat stimulation can be separated in time and still be efficient and efficacious.\",\n \"Even without heat stimulation, the disclosed method of treatment of CKD can be successfully employed for treatment of CKD using long (3-4 hours) daily treatment sessions.\",\n \"A portable, battery powered PEMF device with “daisy” resembling coils in the stimulator makes this strategy easy and efficient.\",\n \"The process of PEMF stimulation of kidney is schematically illustrated in FIGS.\",\n \"5a, 5b and 5c, wherein coils, kidney, magnetic and electric fields are depicted in a rectangular system of coordinates XYZ.\",\n \"Three coils, such as previously described, are sequentially energized by the controller.\",\n \"The directions of respective electrical currents are shown in FIGS.\",\n \"5a-5c by arrows.\",\n \"Coil 209 with two horizontal petals 210 and 211 delivers a pulsed magnetic field B, lines of which are parallel to the ZX plane and normal to Y axis.\",\n \"This magnetic field induces electric field E, lines of which are parallel to the YZ plane and normal to X axis.\",\n \"The electric field E lines are locked on themselves and are induced in the whole area around the coils, including the kidney and surrounding tissues.\",\n \"For simplicity in FIGS.\",\n \"5a-5c, they are shown only in the kidney.\",\n \"Coils 212 and 215 deliver electric field E in planes normal to the Y and Z axes, correspondently.\",\n \"The disclosed system of electromagnetic coils is positioned in one plane but is configured to deliver three-dimensional electromagnetic stimulation (3-D PEMF).\",\n \"This novel arrangement of electromagnetic coils generally resembles a flower, such as a daisy.\",\n \"The “daisy” stimulator provides every cell in a treatment zone with sequential stimulation by electric fields in each of the three directions: Ex, Ey and Ez.\",\n \"The stimulating electric field E is a vector.\",\n \"This fact and the consequences of the vector nature of the stimulating field have not been previously appreciated in the art.\",\n \"FIGS.\",\n \"6a, 6b and 7 schematically illustrate the importance of this feature.\",\n \"Further discussion herein will be conducted with the assumption that the electric pulses applied to a cell are of appropriate amplitude and duration for activation of Ata receptors.\",\n \"This means that the applied electric pulses are about or higher than 1 mV/cm in amplitude and their duration is significantly longer than a time of cell relaxation, which is about 1 microsecond.\",\n \"In contrast, the durations conventionally used in the art are mainly in the range of 25-1000 microseconds.\",\n \"At the beginning of each pulse, a transient period lasting about 1 microsecond takes place.\",\n \"During this period, the mobile ions inside the electrically conductive cytoplasm and the intercellular space outside the cell are redistributed in such a way that the electric field inside the cytoplasm is zero.\",\n \"After the transient period, the cell stays under stationary (static) distribution of the electric field during the rest of the pulse.\",\n \"This redistribution of the ions leads to significant change of electric fields in the membrane.\",\n \"The maximums of electric field Em are located in the parts of membrane that is normal to the applied field and close to zero minimums where the membrane surface is parallel to external field E. The electric field Em in the membrane is defined by the ratio of the cell size to the thickness of membrane and is about 1000 times of the external electric field, comprising approximately 1000 mV/cm.\",\n \"Because the actual electric field in membrane depends on the size of the cell, larger cells are more susceptive to the electric stimulation than smaller ones.\",\n \"For example, the linear size of macrophages is about 2.5 times the size of neutrophils, which means that activation of A2a receptors on macrophages is easier to achieve.\",\n \"And this is good news, because the major damage to kidney in CKD is done by the relatively large macrophage cells.\",\n \"The process of interaction of adenosine receptors with the electric field is illustrated in FIGS.\",\n \"6a and 6b.\",\n \"FIG.\",\n \"6a represents a cell without electric field.\",\n \"For simplicity, only several receptors are shown; in reality, hundreds to thousands of A2a receptors are imbedded in a membrane of one cell.\",\n \"Numeral 601 designates cytosol, the inside volume of the cell separated from the intercellular space by a lipid membrane 602, the thickness of which is exaggerated for clarity of explanation.\",\n \"Numerals 603 and 604 designate adenosine A2a receptors, which are in the inactive state and are unable to bind with adenosine ligands and transduce biological signals into the cell.\",\n \"Adenosine ligands are depicted in FIGS.\",\n \"6a and 6b as AD; they are present around the cell in significant concentration and are available for binding with active A2a receptors.\",\n \"Numeral 605 is an active A2a receptor bound to adenosine ligand.\",\n \"FIG.\",\n \"6b represents the same cell in electrical field E. In the membrane, maximal electric field Em is applied to receptors 603 and 604.This electric field is about 1000 times higher than applied field E and is capable of switching A2a receptors from the inactive to the active state (from OFF to ON).\",\n \"The voltage sensor that switches cellular receptors is a two-position switch.\",\n \"It includes a charged group of atoms capable of moving from one position to another under action of electric field.\",\n \"Only one direction of the electric field parallel to the axis of its sensitivity can affect the position of the electric switch (voltage sensor) of the receptor and turn it ON.\",\n \"The opposite direction of the electric field can only push the charged group of atoms in the OFF position, where it already is, so no switching occurs.\",\n \"Assuming that the direction of switching ON is from inside the cell to outside, the switched ON receptor will be 604.Relocation of the charged group of atoms in the receptor protein molecule causes its conformational change and makes the receptor capable of binding with adenosine ligands.\",\n \"Thus, receptor 604 becomes active, promptly binds with adenosine ligand AD from outside the cell and becomes a bound receptor that transduces the biological signal into the cell and farther along the adenosine signaling pathway.\",\n \"As experimental data on PEMF activation of A2a receptors suggests, the total amount of A2a receptors activated by a one-dimensional electric field is approximately equal to the number of active receptors without electric stimulation.\",\n \"Thus, a one-dimensional electric stimulation causes a two-fold increase of adenosine active receptors, while three-dimensional stimulation causes a four-fold increase of active receptors or doubles the increase of the one-dimensional electric stimulation.\",\n \"FIG.\",\n \"7 schematically illustrates applications of stimulating Ex, Ey and Ez electric fields.\",\n \"An electric field applied along one axis, for example X, practically does not affect the electric field and receptors located in the plane normal to the applied field, YZ plane.\",\n \"The same is true for the other two axis, Y and Z.\",\n \"The receptors located in planes XZ and XY, respectively, are not sensitive to normal electric fields.\",\n \"As shown in FIG.\",\n \"7, sequential stimulation along each of axis X, Y and Z adds three new groups of activated receptors and leads to a four-fold increase of total numbers of active A2a receptors on a cell.\",\n \"These receptors additionally activated by stimulation and ligand bound A2a receptors are relatively stable; they disassociate with ligands and return to a basal state around 2 hours after the end of stimulation.\",\n \"For simplicity in this disclosure, only unipolar electric pulses are discussed.\",\n \"However, stimulating pulses of the opposite polarity can be used as well.\",\n \"In such case, the pulsed electric field is applied in one direction for a period of time long enough to activate receptors and have them bind to the ligands; then the pulsed electric field of opposite direction is applied for the same period of time and the cycle is repeated.\",\n \"The electric field of the opposite direction cannot switch off the activating switch in a receptor that is already bound to a ligand, so activated and bound to ligands receptors will be accumulated on both ends of the stimulated cell along the direction of electric field.\",\n \"The period of stimulation time in one direction can be about 5 to 15 minutes.\",\n \"Bipolar stimulation will activate even more A2a receptors and provide even stronger adenosine anti-inflammation and immune-suppressive signaling.\",\n \"For this bipolar embodiment, a simple circuit for reversing electric currents in coils is added to the apparatus.\",\n \"These types of reversing circuits are well known to those skilled in the art.\",\n \"In a preferred embodiment of the invention, controller 109 provides DC pulses sequentially, one pulse at a time, to coils 209, 212 and 215, thereby creating electric fields along axes X, Y, Z.\",\n \"It is contemplated though, that pulses may be provided to two or three coils simultaneously with different relative amplitudes and polarities.\",\n \"This type of stimulation is more complicated, but allows for producing electric fields in any direction across the cell and can achieve the highest possible activation rate of the receptors A2a.\",\n \"A2a adenosine receptors under applied electric field experience a conformational change that makes them able to bind with adenosine ligands.\",\n \"In an A2a protein molecule there is an electric field sensor comprising a charged group of atoms that operates as a switch creating this conformational transition.\",\n \"Whatever the nature of the electric field sensor is, under influence of electric field E, a charged group of atoms (ion) of the sensor is moving with a velocity Vi defined by the equation: Vi=μE (1) Here constant μ is mobility of the ion.\",\n \"During a stimulating electric pulse, the ion will travel distance ΔL equal to the product of velocity Vi and duration τp: ΔL=Vi τp=μEτp=μ(Eτp) (2) Thus, every stimulating pulse shifts the electric switch of a receptor on a distance ΔL equal to mobility of the ion μ multiplied by Eτp—the product of electric field and pulse duration.\",\n \"Value Eτp sometimes is called “electric impulse”.\",\n \"After accumulating multiple shifts, the switch relocates from the OFF position into the ON position and stays there.\",\n \"From the equation for ΔL, an important scaling law can be inferred: two different pulses produce the same stimulating effect if the product of their amplitudes and durations are the same.\",\n \"This scaling law, which was not appreciated in the previous art, is significant.\",\n \"It gives additional understanding and freedom in selecting durations and amplitudes of PEMF systems.\",\n \"In accordance with specific requirements of his system a designer can select higher electric field amplitudes in combination with shorter durations, or lower amplitudes with longer durations in wide range of values, and still have the same efficiency, provided their electric impulses are equal: Eτp=constant (3) Operation of the PEMF system will now be described.\",\n \"For simplicity, only one stimulating unit 200 will be described.\",\n \"The two stimulating two units (one for each kidney) can be connected to each other in parallel or in series, so their operations are essentially are identical.\",\n \"The applicator belt 102 is positioned on the back of the patient around his/her waist.\",\n \"An operator turns on the system by push-button 111.Controller 109 starts generating DC electric pulses energizing in sequence stimulators 103 and 104.The pulses preferably are short, in tens to hundreds of microseconds, so the current through the coils never reaches the maximum that corresponds to the DC voltage.\",\n \"Exponentially growing currents in coils 209, 212 and 215 creates time varying magnetic fields that induce electric fields in the treatment area.\",\n \"Induced electric fields are circular; their lines are locked on themselves and lie in vertical or horizontal planes as shown in FIGS.\",\n \"5a, 5b and 5c.\",\n \"All coils of the apparatus have a respective free wheel diode connected in parallel to each coil.\",\n \"During a pulse, when a coil is connected to the DC power supply, a significant amount of energy delivered by the power supply is spent creating a magnetic field around the coil.\",\n \"At the end of a pulse, when the coil is cut off from the DC pulse, the magnetic energy induces an electric current in the circuit made by the coil and the companion free wheel diode connected in parallel to the coil.\",\n \"This redirection of magnetic energy into a coil-diode loop protects the circuits from high voltage spikes created by current interruptions in the coil.\",\n \"PEMF stimulation is performed at a constant or variable repetition rate in the range of 5 to 100 Hz.\",\n \"With this rate, the heat deposit in coils is low, in the range of several Watts.\",\n \"It is not sufficient for successful thermal stimulation of the treatment area.\",\n \"Adequate thermal stimulation is achieved by using additional heater 201 placed adjacent to the treatment area and secured together with electromagnetic coils in one stimulating unit 200.Temperature sensor 207 is placed on heater 201 to avoid overheating and to achieve better control of the treatment zone temperature.\",\n \"Controller 109 provides power to the heater 201 by delivering DC pulses with the same frequency (repetition rate) as the PEMF stimulation but, depending on the readings of temperature sensors, pulses with different durations.\",\n \"Actual power delivered to the heaters 201 is controlled by the duration of the pulses.\",\n \"When the temperature reading reaches the value higher or lower than predetermined by the controller, the pulse duration is shortened to allow the applicator to cool down or prolonged to heat it up and keep the temperature stable.\",\n \"The physiological feeling of comfortable warmth in the back may be used as an indication that the temperature is right and should not be increased or decreased.\",\n \"The temperature desired for successful thermal stimulation is about 42-43 degrees Celsius at the patient's skin.\",\n \"In another implementation of invention a sequence of short pulses is supplied by controller 109 to the heater 201 with numbers of heating pulses modulated by the temperature reading and a desired temperature setting.\",\n \"FIG.\",\n \"8 illustrates voltage (a), current and magnetic field (b), electric field (c) and thermal pulses (d and e) used in certain embodiments of the apparatus and kidney treatment method.\",\n \"When a DC step voltage V0 is applied to an inductive coil of the stimulator, the electric current I and the magnetic field B generated by it grow exponentially.\",\n \"At the beginning of a pulse, magnetic field B increases practically linearly (b).\",\n \"So, stimulating field E, which follows B as a derivative function, is almost constant (c).\",\n \"The DC pulse is interrupted by controller 109 with duration of pulse τp being 5-10 times shorter than the time of relaxation of the inductive circuit τ=L/R, where the inductance of the coil is L and its resistance R. In one embodiment of the present invention, the duration of DC pulses applied to the treatment coils is in the range of 5 μs to 100 μs.\",\n \"In another embodiment, the duration of pulses is in the range of 50 μs to 200 μs.\",\n \"In yet another embodiment, duration of pulses can be as high as 1000 μs.\",\n \"The maximum magnetic field Bmax in the treatment zone in one embodiment is in the range of 0.5 mT to 1.0 mT.\",\n \"In another embodiment Bmax is in the range of 1.0 to 10.0 mT.\",\n \"The maximum electric current through coils is 100-500 A.\",\n \"The pulsing frequency (repetition rate) f used for PEMF stimulation and temperature control is in the range of 5 to 100 Hz.\",\n \"In any case, whatever the Bmax and duration of the pulse τp is, the electric field E in the treatment zone should preferably stay in the range of 0.1 mV/cm to 20 mV/cm.\",\n \"A higher amplitude E with a shorter pulse duration τp or lower amplitude with longer pulse duration can be used, but their product Eτp, in accordance with the scaling law should be not less than a minimum value of about 100 μsmV/cm.\",\n \"In the wide range of electrical field amplitudes E and durations τp described above, there is a rule for selection of the right combination of the amplitude and duration: 1000 μsmV/cm>=E τp>=100 μsmV/cm.\",\n \"Repetition rate fin the range of 5 Hz to 100 Hz produces the same biological effects and its choice is not significant for stimulation.\",\n \"FIG.\",\n \"8 graph d) illustrates voltage pulses sent by controller 109 to heater 201.The duration of pulses τh is modulated for stabilization of temperature at a desired level.\",\n \"In the case where a high frequency is used for heating of treatment zone, pulse τh depicts the heating power generated by HF generator.\",\n \"FIG.\",\n \"8 graph e) illustrates sequence of heating pulses when they are short and modulation of applied heat is done by changing their numbers.\",\n \"In one example of treatment regimen for chronic kidney disease, separate sessions of deep heating with ultrasound or HF hypothermia heater or hot bath or sauna 3 to 4 times a week combined with PEMF treatment 3 to 7 times a week can be utilized.\",\n \"While the invention has been described in connection with what is presently considered to be the most practical and preferred example embodiments, it will be apparent to those of ordinary skill in the art that the invention is not to be limited to the disclosed example embodiments.\",\n \"It will be readily apparent to those of ordinary skill in the art that many modifications and equivalent arrangements can be made thereof without departing from the spirit and scope of the present disclosure, such scope to be accorded the broadest interpretation of the appended claims so as to encompass all equivalent structures and products.\",\n \"It is also within the scope of the invention to combine features, functions, advantages and aspects of the various embodiments described herein.\",\n \"Thus, the embodiments of the invention may comprise combinations of aspects of any one or more of these exemplary embodiments.\",\n \"For purposes of interpreting the claims for the present invention, it is expressly intended that the provisions of Section 112, sixth paragraph of 35 U.S.C.\",\n \"are not to be invoked unless the specific terms “means for” or “step for” are recited in a claim.\"\n ]\n]"},"source":{"kind":"string","value":"Patent_15871953"}}},{"rowIdx":4493964,"cells":{"text":{"kind":"list like","value":[["SYSTEMS AND METHODS FOR FORMING PERFORATIONS IN A BARREL STRUCTURE","A drilling system includes a single robotic drilling unit having a drill end effector positioned inside a barrel section configured as a composite sandwich structure having an inner face sheet.","The robotic drilling unit is operable to drill a plurality of perforations into the inner face sheet using the drill end effector.","The robotic drilling unit is configured to index a hole pattern of the perforations to one or more cell walls of a honeycomb core of the composite sandwich structure.","The robotic drilling unit is configured to form the hole pattern in the inner face sheet such that the perforations are located at a spaced distance from the cell walls of the honeycomb core."],["1.A drilling system, comprising: a single robotic drilling unit having a drill end effector positioned inside a barrel section configured as a composite sandwich structure having an inner face sheet; the robotic drilling unit being operable to drill a plurality of perforations into the inner face sheet using the drill end effector; the robotic drilling unit is configured to index a hole pattern of the perforations to one or more cell walls of a honeycomb core of the composite sandwich structure; and the robotic drilling unit is configured to form the hole pattern in the inner face sheet such that the perforations are located at a spaced distance from the cell walls of the honeycomb core.","2.The drilling system of claim 1, wherein: the drill end effector is positioned inside a one-piece engine inlet inner barrel section cured in a single stage.","3.The drilling system of claim 1, wherein: the robotic drilling unit is operated in a manner to drill the perforations such that a percent-open-area in one section of the inner face sheet is different than the percent-open-area in another section of the inner face sheet.","4.The drilling system of claim 1, wherein: the robotic drilling unit has a robotic arm assembly being movable about at least five axes.","5.The drilling system of claim 1, wherein: the robotic drilling unit has a drilling unit base positioned inside the barrel section.","6.A method of fabricating an engine inlet, comprising the steps of: providing an engine inlet inner barrel section configured as a composite sandwich structure having an inner face sheet; drilling, using a single robotic drilling unit, a plurality of perforations in the inner face sheet after final cure of the composite sandwich structure, wherein the drilling comprises indexing a hole pattern of the perforations to one or more cell walls of a honeycomb core of the composite sandwich structure, and positioning the hole pattern such that each perforation is located at a spaced distance from the cell walls; and forming the plurality of perforations in a quantity providing a predetermined percent-open-area of the inner face sheet.","7.The method of claim 6, wherein the step of providing the engine inlet inner barrel section comprises: providing the engine inlet inner barrel section as a one-piece composite sandwich structure.","8.The method of claim 6, wherein the step of drilling the plurality of perforations comprises: drilling the perforations to provide a percent-open-area in one section of the inner face sheet that is different than the percent-open-area in another section of the inner face sheet.","9.The method of claim 6, further comprising: positioning a drilling unit base of the robotic drilling unit inside the engine inlet inner barrel section prior to drilling the plurality of perforations.","10.The method of claim 6, further comprising: indexing the engine inlet inner barrel section and the robotic drilling unit to at least one fixture supporting the barrel section prior to drilling the plurality of perforations.","11.A drilling system, comprising: a single robotic drilling unit having a drill end effector positionable inside a barrel structure supported on a system base; the robotic drilling unit being operable to drill a hole pattern of perforations into an inner surface of the barrel structure using the drill end effector; and the robotic drilling unit is configured to index the perforations relative to internal structure of the barrel structure.","12.The drilling system of claim 11, wherein: the drill end effector is controlled to drill perforations in a vertical row along a height of the barrel structure and/or in a horizontal row along a circumference of the barrel structure.","13.The drilling system of claim 12, wherein: the robotic drilling unit has a vertical base axis; and the drill end effector is rotatable about the vertical base axis to allow the drill end effector to drill another vertical row of perforations adjacent to a previously-drilled vertical row of perforations.","14.The drilling system of claim 11, wherein: the robotic drilling unit is suspended over the barrel structure by an overhead fixture during drilling of the perforations.","15.The drilling system of claim 11, wherein: the barrel structure comprises multiple segments assembled together to form a closed shape.","16.A method of drilling perforations in a barrel structure, comprising the steps of: supporting a barrel structure on a system base; drilling, using a robotic drilling unit having a drill end effector positionable inside the barrel structure, a plurality of perforations into an inner surface of the barrel structure using the drill end effector; and indexing, using the robotic drilling unit, the perforations relative to internal structure of the barrel structure.","17.The method of claim 16, wherein the step of drilling the plurality of perforations comprises: drilling, using the drill end effector, the perforations in a vertical row along a height of the barrel structure and/or in a horizontal row along a circumference of the barrel structure.","18.The method of claim 17, wherein the step of drilling the plurality of perforations comprises: rotating the drill end effector about vertical base axis of the robotic drilling unit to drill another vertical row of perforations adjacent to a previously-drilled vertical row of perforations.","19.The method of claim 16, wherein the step of drilling the plurality of perforations comprises: suspending the robotic drilling unit over the barrel structure by an overhead fixture when drilling the perforations.","20.The method of claim 16, further comprising: positioning a drilling unit base of the robotic drilling unit inside the barrel structure prior to drilling the plurality of perforations."],[" BACKGROUND Commercial airliners are required to meet certain noise standards such as during takeoff and landing.","A large portion of the noise produced by a commercial airliner during takeoff and landing is generated by gas turbine engines commonly used on airliners.","Known methods for reducing the noise level of a gas turbine engine include acoustically treating the engine inlet of the engine nacelle.","In this regard, the inner barrel section of a gas turbine engine inlet may be provided with a plurality of relatively small perforations formed in the walls of the inner barrel section.","The perforations absorb some of the noise that is generated by fan blades rotating at high speed at the engine inlet, and thereby reduce the overall noise output of the gas turbine engine.","Conventional methods for forming perforations in acoustic structures such as the barrel section include forming the inner wall of the barrel section as a separate component, followed by forming the perforations in the inner wall.","The inner wall may then be assembled with other components that make up the barrel section, which is then assembled with the nacelle of the gas turbine engine.","Unfortunately, such conventional methods for forming acoustic structures include operations that may result in the blockage of some of the perforations after the perforations have been formed.","Conventional methods for forming acoustic structures may also result in missing perforations.","Such blocked perforations or missing perforations may reduce the percent-open-area (POA) of the inner wall (e.g., the total area of the perforations as a percentage of the surface area of the inner wall) which is a characteristic of acoustic structures for measuring their overall effectiveness in absorbing or attenuating noise.","Furthermore, conventional methods of forming perforations in acoustic structures are time-consuming processes that add to the production schedule and cost.","As can be seen, there exists a need in the art for a system and method for forming perforations in an acoustic structure which minimizes or eliminates the occurrence of blocked or missing perforations, and which may be performed in a timely and cost-effective manner."],[" SUMMARY The above-noted needs associated with forming perforations in an acoustic structure such as an engine inlet are specifically addressed and alleviated by the present disclosure which provides a drilling system that may include a plurality of robotic drilling units.","Each one of the robotic drilling units may include a drill end effector positioned inside a barrel section of an engine inlet.","The barrel section may be configured as a composite sandwich structure having an inner face sheet.","The robotic drilling units may be operable in synchronized movement with one another to drill a plurality of perforations into the inner face sheet using the drill end effectors in a manner providing a predetermined percent-open-area of the inner face sheet.","Also disclosed is a method of fabricating an engine inlet.","The method may include providing an engine inlet inner barrel section configured as a composite sandwich structure having an inner face sheet, a core, and an outer face sheet.","The method may further include robotically drilling a plurality of perforations in the inner face sheet after final cure of the composite sandwich structure.","The method may additionally include forming the plurality of perforations in a quantity providing a predetermined percent-open-area of the inner face sheet.","In a further embodiment, disclosed is a method of fabricating an engine inlet including the step of providing an engine inlet inner barrel section configured as a one-piece composite sandwich structure having an inner face sheet, an outer face sheet, and a honeycomb core.","The composite sandwich structure may be formed in a single stage cure wherein the inner face sheet, the core, and the outer face sheet may be co-cured and/or co-bonded in a single operation.","The method may include drilling, using a plurality of robotic drilling units, a plurality of perforations in the inner face sheet after final cure of the composite sandwich structure.","The method may further include operating the plurality of robotic drilling units in synchronized movement with one another to simultaneously drill the plurality of perforations.","The method may also include forming the plurality of perforations in a quantity providing a predetermined percent-open-area of the inner face sheet.","The features, functions and advantages that have been discussed can be achieved independently in various embodiments of the present disclosure or may be combined in yet other embodiments, further details of which can be seen with reference to the following description and drawings below."],["CROSS-REFERENCE TO RELATED APPLICATIONS The present application is a continuation application of and claims priority to pending U.S. application Ser.","No.","15/155,018 filed on May 15, 2016, and entitled SYSTEM FOR FORMING PERFORATIONS IN A BARREL SECTION, which is a divisional application of and claims priority to U.S. application Ser.","No.","14/012,243 filed on Aug. 28, 2013, now U.S. Pat.","No.","9,370,827, issued on Jun.","21, 2016, and entitled SYSTEM AND METHOD FOR FORMING PERFORATIONS IN A BARREL SECTION, the entire contents of which is expressly incorporated by reference herein.","FIELD The present disclosure relates generally to production of acoustic treatment of structures and, more particularly, to the forming of acoustic perforations in an engine inlet barrel section.","BACKGROUND Commercial airliners are required to meet certain noise standards such as during takeoff and landing.","A large portion of the noise produced by a commercial airliner during takeoff and landing is generated by gas turbine engines commonly used on airliners.","Known methods for reducing the noise level of a gas turbine engine include acoustically treating the engine inlet of the engine nacelle.","In this regard, the inner barrel section of a gas turbine engine inlet may be provided with a plurality of relatively small perforations formed in the walls of the inner barrel section.","The perforations absorb some of the noise that is generated by fan blades rotating at high speed at the engine inlet, and thereby reduce the overall noise output of the gas turbine engine.","Conventional methods for forming perforations in acoustic structures such as the barrel section include forming the inner wall of the barrel section as a separate component, followed by forming the perforations in the inner wall.","The inner wall may then be assembled with other components that make up the barrel section, which is then assembled with the nacelle of the gas turbine engine.","Unfortunately, such conventional methods for forming acoustic structures include operations that may result in the blockage of some of the perforations after the perforations have been formed.","Conventional methods for forming acoustic structures may also result in missing perforations.","Such blocked perforations or missing perforations may reduce the percent-open-area (POA) of the inner wall (e.g., the total area of the perforations as a percentage of the surface area of the inner wall) which is a characteristic of acoustic structures for measuring their overall effectiveness in absorbing or attenuating noise.","Furthermore, conventional methods of forming perforations in acoustic structures are time-consuming processes that add to the production schedule and cost.","As can be seen, there exists a need in the art for a system and method for forming perforations in an acoustic structure which minimizes or eliminates the occurrence of blocked or missing perforations, and which may be performed in a timely and cost-effective manner.","SUMMARY The above-noted needs associated with forming perforations in an acoustic structure such as an engine inlet are specifically addressed and alleviated by the present disclosure which provides a drilling system that may include a plurality of robotic drilling units.","Each one of the robotic drilling units may include a drill end effector positioned inside a barrel section of an engine inlet.","The barrel section may be configured as a composite sandwich structure having an inner face sheet.","The robotic drilling units may be operable in synchronized movement with one another to drill a plurality of perforations into the inner face sheet using the drill end effectors in a manner providing a predetermined percent-open-area of the inner face sheet.","Also disclosed is a method of fabricating an engine inlet.","The method may include providing an engine inlet inner barrel section configured as a composite sandwich structure having an inner face sheet, a core, and an outer face sheet.","The method may further include robotically drilling a plurality of perforations in the inner face sheet after final cure of the composite sandwich structure.","The method may additionally include forming the plurality of perforations in a quantity providing a predetermined percent-open-area of the inner face sheet.","In a further embodiment, disclosed is a method of fabricating an engine inlet including the step of providing an engine inlet inner barrel section configured as a one-piece composite sandwich structure having an inner face sheet, an outer face sheet, and a honeycomb core.","The composite sandwich structure may be formed in a single stage cure wherein the inner face sheet, the core, and the outer face sheet may be co-cured and/or co-bonded in a single operation.","The method may include drilling, using a plurality of robotic drilling units, a plurality of perforations in the inner face sheet after final cure of the composite sandwich structure.","The method may further include operating the plurality of robotic drilling units in synchronized movement with one another to simultaneously drill the plurality of perforations.","The method may also include forming the plurality of perforations in a quantity providing a predetermined percent-open-area of the inner face sheet.","The features, functions and advantages that have been discussed can be achieved independently in various embodiments of the present disclosure or may be combined in yet other embodiments, further details of which can be seen with reference to the following description and drawings below.","BRIEF DESCRIPTION OF THE DRAWINGS These and other features of the present disclosure will become more apparent upon reference to the drawings wherein like numbers refer to like parts throughout and wherein: FIG.","1 is a perspective illustration of an aircraft; FIG.","2 is a perspective illustration of a nacelle of a gas turbine engine of the aircraft of FIG.","1; FIG.","3 is a perspective illustration of an inner barrel section of an engine inlet of the gas turbine engine of FIG.","2; FIG.","4 is a cross-sectional illustration of a leading edge of the engine inlet of the gas turbine engine of FIG.","2; FIG.","5 is a perspective illustration of an embodiment of a drilling system for forming perforations in a barrel section; FIG.","6 is a perspective illustration of the drilling system with the barrel section shown in phantom lines to illustrate a plurality of robotic drilling units of the drilling system; FIG.","7 is a side view of the drilling system; FIG.","8 is the top view of the drilling system; FIG.","9 is a side view of one of the robotic drilling units forming a hole pattern along an inner face sheet of the inner barrel section; FIG.","10 is a perspective illustration of a drill end effector forming a perforation in an inner face sheet of a composite sandwich structure of the inner barrel section; FIG.","11 is a cross sectional illustration taken along line 11 of FIG.","10 and illustrating a drill bit of the drill end effector drilling a perforation in the inner face sheet of the composite sandwich structure; FIG.","12 is a block diagram of an embodiment of the drilling system; FIG.","13 is an illustration of a flow chart including one or more operations that may be implemented in a method of fabricating an engine inlet; FIG.","14 is a flow diagram of an aircraft manufacturing and service methodology; and FIG.","15 is a block diagram of an aircraft.","DETAILED DESCRIPTION Referring now to the drawings wherein the showings are for purposes of illustrating various embodiments of the present disclosure, shown in FIG.","1 is a perspective illustration of an aircraft 100.The aircraft 100 may include a fuselage 102 extending from a nose to an empennage 104.The empennage 104 may include one or more tail surfaces for directional control of the aircraft 100.The aircraft 100 may include a pair of wings 106 extending outwardly from the fuselage 102.In FIG.","1, the aircraft 100 may include one or more propulsion units which, in an embodiment, may be supported by the wings 106.Each one of the propulsion units may be configured as a gas turbine engine 108 having a core engine (not shown) surrounded by a nacelle 110.The nacelle 110 may include an engine inlet 114 and a fan cowl 118 surrounding one or more fans (not shown) mounted on a forward end (not shown) of the core engine.","The nacelle 110 may have an exhaust nozzle 112 (e.g., a primary exhaust nozzle and a fan nozzle) at an aft end (not shown) of the gas turbine engine 108.FIG.","2 illustrates an embodiment of a gas turbine engine 108 having an engine inlet 114.The engine inlet 114 may include a leading edge 116 and an inner barrel section 120 located aft of the leading edge 116 of the engine inlet 114.The inner barrel section 120 may provide a boundary surface or wall for directing airflow (not shown) entering the engine inlet 114 and passing through the gas turbine engine 108.The inner barrel section 120 may be located in relatively close proximity to one or more fans (not shown).","In this regard, the inner barrel section 120 may also be configured to serve as an acoustic structure having a plurality of perforations 136 (FIG.","9) in an inner face sheet 134 (FIG.","10) of the inner barrel section 120 for absorbing noise generated by the rotating fans and/or noise generated by the airflow entering the engine inlet 114 and passing through the gas turbine engine 108.As described below, the total area of the perforations 136 in the inner face sheet 134 may be expressed as percent-open-area 144 (FIG.","9) which represents the total area of the perforations 136 as a percentage of the surface area of the inner face sheet 134.The percent-open-area 141 may be a characteristic for measuring the overall effectiveness or acoustic-attenuating capability of the inner barrel section 120.During the design and/or development of the aircraft 100, a specific, a predetermined percent-open-area 144 (FIG.","9) may be selected for the inner barrel section 120 to meet acoustic performance requirements of the engine inlet 114.FIG.","3 is a perspective illustration of an embodiment of an inner barrel section 120 of an engine inlet 114.In the embodiment shown, the barrel section 120 may have a diameter (not shown) of up to 5-8 feet or larger, and a length (not shown) extending from an aft edge 126 to a forward edge 124 of up to 2-3 feet or longer.","However, the barrel section 120 may be provided in any size, shape, and configuration, without limitation.","The inner barrel section 120 may be formed as a composite sandwich structure 122 having an inner face sheet 134 and an outer face sheet 132 separated by a core 128.The inner face sheet 134 and/or the outer face sheet 132 may be formed of composite material including fiber-reinforced polymeric matrix material such as graphite-epoxy, fiberglass-epoxy, or other composite material.","Alternatively, the inner face sheet 134 and/or the outer face sheet 132 may be formed of metallic material such as titanium, steel, or other metallic materials or combinations of materials.","The core 128 may comprise honeycomb core having a plurality of cells 130 oriented generally transverse to the inner face sheet 134 and outer face sheet 132.The core 128 may be formed of metallic material and/or non-metallic material and may include aluminum, titanium, aramid, fiberglass, or other core materials.","In FIG.","3, in an embodiment, the engine inlet 114 may comprise a one-piece engine inlet 114 inner barrel section 120.The inner barrel section 120 may be fabricated from raw materials (not shown) and assembled and cured in one or more stages.","For example, the inner face sheet 134 and the outer face sheet 132 may be separately formed by laying up dry fiber fabric (not shown) or resin-impregnated ply material (i.e., pre-preg) on separate layup mandrels (not shown) and separately cured, followed by bonding the inner face sheet 134 and the outer face sheet 132 to the core 128.Alternatively, the inner barrel section 120 may be fabricated in a single-stage cure process wherein the inner face sheet 134 may be laid up on a layup mandrel (not shown), after which the core 128 may be laid up over the inner face sheet 134, followed by laying up the outer face sheet 132 over the core 128.The layup assembly (not shown) may be cured in a single stage, after which the drilling system 200 (FIG.","5) disclosed herein may be implemented for forming perforations 136 (FIG.","9) in the inner face sheet 134.In an embodiment described in greater detail below, the drilling system 200 (FIG.","5) disclosed herein may be implemented for forming a plurality of perforations 136 (FIG.","9) in the inner face sheet 134 (FIG.","9) of the assembled barrel section 120.For example, the drilling system 200 (FIG.","5) disclosed herein may include a plurality of robotic drilling units 208 (FIG.","8) positioned inside the barrel section 120 for robotically drilling a plurality of the perforations 136 in the inner face sheet 134 after final cure of the composite sandwich structure 122 engine inlet inner barrel section 120.The perforations 136 (FIG.","9) may be formed in a size and quantity to provide a predetermined percent-open-area 144 for the inner barrel section 120 to allow the inner barrel section 120 to meet acoustic performance requirements of the engine inlet 114.In FIG.","3, the inner barrel section 120 may comprise a unitary structure having closed shape with a generally cylindrical configuration.","However, in an embodiment, the inner barrel section 120 may be formed as multiple segments (not shown) assembled together to form a closed shape.","The inner barrel section 120 may be provided in a contoured cross-sectional shape (not shown) to promote airflow (not shown) through the gas turbine engine 108.In this regard, when viewed along a circumferential direction, the inner barrel section 120 may have a cross section that may be complexly curved and may be formed complementary to the shape of the engine inlet 114 leading edge 116 at a forward edge 124 of the inner barrel section 120, and complementary to the shape of the interior nacelle surfaces (not shown) aft of the inner barrel section 120.However, the inner barrel section 120 may be provided in any shape including a simple cylindrical shape and/or a conical shape.","FIG.","4 is a cross-sectional illustration of the leading edge 116 of the engine inlet 114 showing the composite sandwich construction including the circumferential inner face sheet 134, the circumferential outer face sheet 132, and the core 128 separating the inner face sheet 134 and outer face sheet 132 of the barrel section 120.The forward edge 124 of the inner barrel section 120 may be coupled to or may interface with the engine inlet 114 leading edge 116.The aft edge 126 of the inner barrel section 120 may be coupled to or may interface with the nacelle interior (not shown).","In the embodiment shown, the inner face sheet 134, the core 128, and the outer face sheet 132 have a complexly-curved cross sectional shape to promote efficient airflow through the nacelle 110.FIG.","5 is an illustration of an embodiment of a drilling system 200 as may be implemented for forming perforations 136 (FIG.","9) in a barrel section 120 such as the inner barrel section 120 of an engine inlet 114 of a gas turbine engine 108 (FIG.","3).","However, the drilling system 200 disclosed herein may be implemented for forming perforations 136 (FIG.","9) in any type of barrel structure for any application, without limitation.","For example, the drilling system 200 may be implemented for forming perforations 136 (FIG.","9) in a barrel section of any one of a variety of different types of commercial, civilian, and military aircraft 100 (FIG.","1).","Furthermore, the drilling system 200 may be implemented for forming perforations 136 (FIG.","9) in the barrel section 120 of a gas turbine engine 108 (FIG.","1) of rotorcraft, hovercraft, or in any other vehicular or non-vehicular application wherein a predetermined quantity of acoustic perforations 136 (FIG.","9) are required in a barrel section 120 for acoustic attenuating purposes.","In FIG.","5, the drilling system 200 is shown mounted within an interior of a barrel section 120.The drilling system 200 may include robotic drilling units 208 that advantageously allow for forming perforations 136 (FIG.","9) in a barrel section 120 to provide the predetermined percent-open-area 144 (FIG.","9) of the inner face sheet 134 of the barrel section 120.As indicated above, the predetermined percent-open-area 144 may be determined during the design and/or development of the aircraft 100 (FIG.","1) to meet acoustic performance requirements of the engine inlet 114.The drilling system 200 disclosed herein advantageously allows for consistently forming perforations 136 in the inner face sheets 134 of composite sandwich structure 122 barrel sections 120 to provide a predetermined percent-open-area 144 (FIG.","9) in the inner face sheet 134.In this regard, the drilling system 200 advantageously overcomes the drawbacks associated with conventional methods for forming perforations (not shown) in conventional inner barrel sections (not shown) such as the above-mentioned drawbacks associated with blocked perforations (not shown) due to subsequent processing of a conventional inner barrel section (not shown) in a conventional multi-stage forming process (not shown), and/or due to missing perforations (not shown) during conventional perforating (not shown) of the inner skin (not shown) of a conventional inner barrel section.","Such blocked perforations or missing perforations may reduce the predetermined percent-open-area 144 of the inner skin of the conventional inner barrel section which may reduce the acoustic performance of the engine inlet 114.In FIG.","5, a plurality of robotic drilling units 208 (e.g., two robotic drilling units 208, three robotic drilling units 208, etc.)","may be supported on a system base 202.Each one of the robotic drilling units 208 may include a drill end effector 234.In an embodiment, the system base 202 may comprise a relatively rigid structure and may include a tooling fixture, a shop floor, or a table configured to support the plurality of robotic drilling units 208.In addition, the system base 202 may be configured to support the barrel section 120.However, the drilling system 200 may be provided in an alternative embodiment wherein the plurality of robotic drilling units 208 are supported by a structure that is located separate from the barrel section 120.For example, the plurality of robotic drilling units 208 may be suspended over the inner barrel section 120 such as by an overhead fixture (not shown) in a manner such that the drill end effectors 234 may be positioned within the interior of the barrel section 120, and/or the plurality of robotic drilling units 208 may be mounted inside or outside of the barrel section 120.FIG.","6 is a perspective illustration of the plurality of robotic drilling units 208 positioned on the system base 202 and mounted within relatively close proximity to one another such that the barrel section 120 circumscribes the plurality of robotic drilling units 208 when the barrel section 120 is mounted to the system base 202.Although four (4) robotic drilling units 208 are shown, any number may be provided.","In an embodiment, the robotic drilling units 208 may be mounted in an array.","For example, each one of the robotic drilling units 208 may include a drilling unit base 212 (FIG.","7).","The drilling unit bases 212 (FIG.","7) may be mounted to the system base 202 in a circular array 206 (FIG.","8) such that when the barrel section 120 is mounted to the system base 202, each one of the drilling unit bases 212 (FIG.","7) is positioned at substantially the same distance from the inner face sheet 134 of the barrel section 120.FIG.","7 is a side view of an embodiment of the drilling system 200.The barrel section 120, shown in phantom lines, may be supported on one fixture 204 or multiple fixtures 204.The fixtures 204 may comprise spacers sized and configured to position the barrel section 120 at a vertical location that is complementary to the movement capability of the drill end effectors 234 of the robotic drilling units 208.In this regard, the fixtures 204 may be configured such that the drill end effectors 234 may form perforations 136 (FIG.","9) in the inner face sheet 134 of the barrel section 120 at any vertical location between the forward edge 124 of the barrel section 120 and the aft edge 126 of the barrel section 120.The fixtures 204 may be comprised of a rigid material and may be configured as simple blocks (not shown) formed of metallic or polymeric material and which may be fixedly coupled to the system base 202.The fixtures 204 may extend vertically along any portion of the height of the barrel section and horizontally along any portion of the circumference of the barrel section 120.FIG.","8 is a top view of the drilling system 200 illustrating an arrangement of the robotic drilling units 208.Each one of the robotic drilling units 208 may include a robotic arm assembly 210 having a drill end effector 234 mounted on an end of the robotic arm assembly 210.The robotic drilling units 208 may be mounted such that drilling unit bases 212 are positioned adjacent to a center of the array of the robotic drilling units 208.In an embodiment, the drilling system 200 may comprise a single robotic drilling unit 208 or a plurality of robotic drilling units 208.For example, the drilling system 200 may include two (2) or more robotic drilling units 208 having drilling unit bases 212 which may be arranged at a predetermined spacing relative to one another, such as a substantially equiangular spacing relative to one another.","Referring still to FIG.","8, the plurality of robotic drilling units 208 may be configured (e.g., programmed) to drill perforations 136 (FIG.","9) within substantially equivalent arc segments 142 of the barrel section 120.For example, for the embodiment shown, the plurality of robotic drilling units 208 may comprise four (4) robotic drilling units 208.The drilling unit bases 212 may be arranged such that the drilling unit bases 212 are positioned at an angular spacing of approximately ninety degrees relative to one another.","In an embodiment, each one of the robotic drilling units 208 may be configured to drill perforations 136 (FIG.","9) within an approximate ninety-degree arc segment 142 of the barrel section 120.However, the robotic drilling units 208 may be positioned at any location relative to one another and may be configured to form perforations 136 (FIG.","9) at any circumstantial location or any vertical location of the barrel section 120.In FIG.","8, the drill end effector 234 of each one of the robotic drilling units 208 may be oriented generally radially outwardly away from the drilling unit base 212.The drilling unit bases 212 may be positioned to provide space for movement of the robotic arm assemblies 210 during operation of the drilling system 200.In this regard, the robotic drilling units 208 are simultaneously operable in synchronized movement with one another in a manner allowing the drill end effectors 234 to simultaneously drill a plurality of perforations 136 (FIG.","9) in the barrel section 120.The robotic drilling units 208 may be programmed to avoid collisions with one another and with the barrel section 120 during the synchronized movement with one another.","FIG.","9 is a side view of one of the robotic drilling units 208 showing the barrel section 120 supported on fixtures 204 and illustrating a drill bit 236 of one of the drill end effectors 234 forming perforations 136 in a predetermined hole pattern 140 along the inner face sheet 134 of the inner barrel section 120.In this regard, in an embodiment, each one of the robotic drilling units 208 may be indexed to the system base 202.The barrel section 120 may also be indexed to the system base 202 such as with fixtures 204 to provide a means for the drill end effector 234 to form perforations 136 within a relatively small positional tolerance relative to a circumferential direction (not shown) of the barrel section 120 and relative to an axial direction (not shown) of the barrel section 120.However, the barrel section 120 and the robotic drilling units 208 may be indexed relative to one another by other means, and are not necessarily limited to being indexed to the system base 202.In FIG.","9, the robotic drilling units 208 may be operated in a manner to drill the perforations 136 in the inner face sheet 134 such that a percent-open-area 144 in one section 148 of the inner face sheet 134 is different than the percent-open-area 144 in another section 150 of the inner face sheet 134.In this regard, the robotic drilling units 208 may be programmed to drill perforations 136 to provide a greater percent-open-area 144 in a first section 148 of the inner face sheet 134 relative to drilling perforations 136 to provide a lower percent-open-area 144 in a second section 150 of the inner face sheet 134.For example, the second section 150 with a smaller percent-open-area 144 may be located adjacent to a forward edge 124 and/or an aft edge 126 of the barrel section 120, and the first section 148 with a larger percent-open-area 144 may be located in an interior region (not shown) of the inner barrel section 120 between the forward edge 124 and the aft edge 126.However, the robotic drilling 208 units may drill the perforations 136 such that the percent-open-area 144 in the inner face sheet 134 is different at different circumferential sections (not shown) of the barrel section 120, or the percent-open-area 144 of the inner barrel section 120 may vary in a different manner than the above-noted embodiments.","In FIG.","9, one or more of the robotic drilling units 208 may have a six-axis robotic arm assembly 210 which may allow for accurately positioning the drill end effector 234 at any desired location and orientation along the inner face sheet 134.As the drill end effector 234 is positioned and oriented at a desired location of a perforation 136, the drill end effector 234 may be moved axially to drive the rotating drill bit 236 into the inner face sheet 134 to form a perforation 136.Alternatively, the drill end effector 234 may be positioned at a desired location of a perforation 136 on the inner face sheet 134, and the drill end effector 234 may axially drive the rotating drill bit 236 along a direction of the drill bit axis 238 to drill the perforation 136 in the inner face sheet 134.In an embodiment, the six-axis robotic arm assembly 210 may include a first arm 220 which may be attached to the drilling unit base 212 at a shoulder joint 216.The first arm 220 may be attached to a second arm 226 at an elbow joint 222.The second arm 226 may be attached to the drill end effector 234 at a wrist joint 230.In FIG.","9, the drilling unit base 212 may be configured to rotate about a vertical base axis 214 relative to the system base 202.The first arm 220 may be configured to rotate about a shoulder axis 218 of the shoulder joint 216 coupling the first arm 220 to the drilling unit base 212.The second arm 226 may be configured to rotate about an elbow axis 224 of the elbow joint 222 coupling the second arm 226 to the first arm 220.A portion of the second arm 226 may also be configured to swivel about a second arm axis 228 extending along a direction from the elbow joint 222 to the wrist joint 230.The drill end effector 234 may be configured to rotate about a wrist axis 232 of the wrist joint 230.In addition, the drill end effector 234 may be configured to rotate about an end effector axis 235 which may be generally parallel to the drill bit axis 238.In an optional embodiment, the end effector may be configured to linearly translate the drill bit 236 along a drill bit axis 238 such as when drilling a perforation 136 in the inner face sheet 134.In FIG.","9, the robotic arm assembly 210 is shown in a six-axis embodiment.","However, the robotic arm assembly 210 may be provided in alternative arrangements.","For example, the robotic arm assembly 210 may be provided in a 3-axis embodiment (not shown), a 4-axis embodiment (not shown), or a 5-axis embodiment (not shown).","In addition, the robotic arm assembly 210 may be provided in an embodiment having more than six (6) axes.","Furthermore, the robotic arm assembly 210 may be configured as a motion control system (not shown), a rigid frame (not shown) having linear axes along which the end effector is movable, or any other type of motion control device for controlling a drill end effector 234 for drilling perforations 136.In addition, each robotic arm assembly 210 may include more than one drill end effector 234.Furthermore, each drill end effector 234 may have more than one drill bit 236 for simultaneously forming perforations 136.FIG.","10 shows a drill end effector 234 forming a perforation 136 in the inner face sheet 134 of a composite sandwich structure 122 of the inner barrel section 120.Advantageously, the drilling system 200 provides a means for accurate and rapid placement of the drill end effector 234 for drilling perforations 136 in a predetermined hole pattern 140 (FIG.","9).","For example, in an embodiment, each one of the drill end effectors 234 of a robotic drilling unit 208 may be configured to form up to three (3) or more perforations 136 per second, per drill end effector 234.In an embodiment, the drill end effector 234 may be provided with a drill bit 236 configured to form acoustic perforations 136 having a hole diameter of approximately 0.010 to 0.10 inch, although larger or smaller perforations 136 are possible based on the drill bit 236 diameter.","In FIG.","10, for forming perforations 136 in a composite inner face sheet 134, the drill end effector 234 may be configured to drive the drill bit 236 at a feed rate of approximately 20-60 inches per minute, and at rotational speeds of between approximately 20,000 to 40,000 rpm, although larger or smaller feed rates and larger or smaller rotational speeds may be selected based on the material being drilled and the composition of the drill bit 236.The drill bit 236 feed rate and the drill bit 236 rotational speed may be controlled to minimize drill bit 236 wear, and such that the perforations 136 may meet tight tolerances for roundness and other hole parameters.","Significantly, each robotic drilling unit 208 is configured to quickly and accurately form hole patterns 140 (FIG.","9) at a relatively small center-to-center positional tolerance (i.e., perforation-to-perforation) such as a center-to-center positional tolerance of approximately 0.010 inch or less.","However, the center-to-center positional tolerance may be greater than 0.010 inch, such as up to approximately 0.050 inch or greater.","In FIG.","10, one or more of the drill end effectors 234 may include a vacuum attachment 240 for removing debris (not shown) such as dust and chips that may be generated during the drilling of the perforations 136.The vacuum attachment 240 may have a hollow (not shown) or open portion (not shown) that may be positioned around the drill bit 236 and may be placed adjacent to or in contact with the inner face sheet 134 when the drill bit 236 contacts the inner face sheet 134 and drills a perforation 136.The vacuum attachment 240 may include a vacuum port 242 for connection to a vacuum source (not shown) using a vacuum hose (not shown) for drawing a vacuum 244 on the vacuum attachment 240 for drawing debris (not shown) from the area surrounding the perforation 136.In FIG.","10, in a further embodiment, the drilling system 200 may be provided with an automated bit changer (not shown) for changing the drill bits 236 using robotic control.","In this manner, worn drill bits 236 may be replaced after drilling a predetermined quantity of perforations 136.For example, an automated bit changer (not shown) may replace each drill bit 236 after drilling anywhere from approximately 1,000 to 30,000 perforations 136, although the drill bits 236 may be replaced after drilling a smaller or larger quantity of perforations 136 than the above-noted range.","Depending upon the size (e.g., diameter and height) of the inner barrel section 120 and the total quantity of robotic drilling units 208 that are used, each drill end effector 234 may undergo 1 to 20 or more drill bit changes per barrel section 120.Referring briefly to FIG.","9, in an embodiment, the drill end effectors 234 may be controlled to drill perforations 136 in a hole pattern 140 of vertical rows (not shown) along a height of the barrel section 120.In this regard, each drill end effector 234 may drill a vertical row of perforations 136, and the drill end effector 234 may be rotated about the vertical base axis 214 to allow the drill end effector 234 to drill another vertical row of perforations 136 adjacent to the previously-drilled vertical row of perforations 136.The drill end effectors 234 may also be controlled to drill perforations 136 in horizontal rows (not shown), or in any other direction or combination of directions.","As indicated above, the robotic arm assemblies 210 may be operated in a synchronized manner such that the drill end effectors 234 are maintained at a generally equiangular spacing from one another during the simultaneous drilling of perforations 136 in the inner face sheet 134 of the barrel section 120.For example, for a drilling system 200 having four (4) robotic drilling units 208, the drill end effectors 234 may be maintained at an angular separation of approximately ninety (90) degrees from each other during the simultaneous drilling of perforations 136 in the inner face sheet 134.FIG.","11 is a cross sectional view of a drill bit 236 of the drill end effector 234 forming a perforation 136 in the inner face sheet 134 of a composite sandwich structure 122.In an embodiment, the drill end effector 234 may include a drill stop (not shown) to control a depth 138 at which the drill bit 236 extends into the composite sandwich structure 122, and minimize the depth 138 of the drill bit 236 into the core 128 material.","Furthermore, a drill stop (not shown) may stabilize the drill end effector 234 when drilling the perforation 136 to prevent lateral movement of the drill bit 236 relative to the perforation 136, and which may advantageously avoid a non-conformance regarding the positional tolerance, roundness tolerance, or other tolerance parameters of the perforation 136.In an embodiment, each drill end effector 234 may include a non-contact method of gauging the depth 138 at which each perforation 136 is drilled such as by using a laser device (not shown), an ultrasonic device (not shown), and other non-contact device.","The depth 138 of drilling may also be controlled by a controller (not shown) controlling the drill end effector 234.FIG.","12 is a block diagram of an embodiment of a drilling system 200.The drilling system 200 may include a plurality of robotic drilling units 208.Each one of the robotic drilling units 208 may include a robotic arm assembly 210 as described above.","A drill end effector 234 may be coupled to the end of each one of the robotic arm assemblies 210 of each robotic drilling unit 208.The robotic drilling units 208 may be simultaneously operable in synchronized movement with one another such that the drill end effectors 234 may simultaneously drill a plurality of perforations 136 in the barrel section 120.In FIG.","12, the barrel section 120 may comprise an inner barrel section 120 of an engine inlet 114 such as of a gas turbine engine 108 (FIG.","3), as indicated above.","In an embodiment, the barrel section 120 may be formed as a composite sandwich structure 122.The composite sandwich structure 122 may have an outer face sheet 132, a core 128, and an inner face sheet 134 which may be assembled or bonded together to form a one-piece engine inlet inner barrel section 120.The drilling system 200 may rapidly and accurately form a plurality of perforations 136 in a predetermined hole pattern of perforations 136 (FIG.","9) in the inner face sheet 134 to provide a predetermined percent-open-area 144 for the inner barrel section 120 to meet acoustic performance requirements.","FIG.","13 is an illustration of a flow chart including one or more operations that may be included in a method 300 of fabricating an engine inlet 114 (FIG.","3).","Step 302 of the method may include providing a barrel section 120 (FIG.","3) such as an inner barrel section 120 (FIG.","3) of an engine inlet 114 (FIG.","3).","As indicated above, the inner barrel section 120 (FIG.","3) may be provided as a one-piece composite sandwich structure 122 (FIG.","3).","In such a composite sandwich structure 122 (FIG.","3), the inner face sheet 134 (FIG.","3) may be formed of composite material and the outer face sheet 132 (FIG.","3) may be formed of composite material (e.g., fiber-reinforced polymeric matrix material).","However, the inner face sheet 134 (FIG.","3) and/or the outer face sheet 132 (FIG.","3) may be formed of metallic material, or a combination of metallic material and non-metallic material.","As indicated above, the core 128 (FIG.","3) may comprise honeycomb core formed of metallic material and/or non-metallic material and may include aluminum, titanium, aramid, fiberglass, or other core materials.","The engine inlet 114 (FIG.","3) inner barrel section 120 (FIG.","3) may be fabricated as a one-piece composite sandwich structure 122 (FIG.","3) formed in a single-stage cure.","As described above, the barrel section 120 (FIG.","3) may be provided in a single-stage cure wherein the inner face sheet 134 (FIG.","3), the core 128 (FIG.","3), and the outer face sheet 132 (FIG.","3) may be laid up on a layup mandrel, after which heat and/or pressure may be applied to the layup (not shown) for a predetermined time for curing in a single stage.","Step 304 of the method 300 of FIG.","13 may include mounting and indexing the inner barrel section 120 (FIG.","7) to a system base 202 (FIG.","7).","In this regard, the inner barrel section 120 (FIG.","7) may be supported on a plurality of fixtures 204 (FIG.","7) which may be mounted to the system base 202 (FIG.","7).","The fixtures 204 (FIG.","7) may fixedly position the inner barrel section 120 (FIG.","7) on the system base 202 (FIG.","7) which may comprise a table (not shown), an assembly (not shown), or other relatively rigid structure configured to support the inner barrel section 120 (FIG.","7) and prevent movement thereof during the drilling of the perforations 136 (FIG.","9) in the inner barrel section 120 (FIG.","7).","As indicated above, the fixtures 204 may be positioned at spaced intervals around a perimeter (not shown) of the inner barrel section 120 such as along the aft edge 126 (FIG.","9) or forward edge 124 (FIG.","9) of the inner barrel section 120.The fixtures 204 may include mechanical indexing features (not shown) to index the inner barrel section 120 to the fixtures 204.A laser system (not shown) may be implemented to aid in positioning the inner barrel section 120 relative to the fixtures 204.The inner barrel section 120 may be mechanically coupled to the fixtures 204 to rigidly clamp the inner barrel section 120 in position.","Step 306 of the method 300 of FIG.","13 may include indexing the plurality of robotic drilling units to the system base 202 (FIG.","7) as shown in FIG.","7.In an embodiment, each one of the plurality of robotic drilling units 208 (FIG.","7) may have a drilling unit base 212 (FIG.","7) that may be directly mounted to the system base 202 and indexed to the system base 202 and/or to the fixtures 204 (FIG.","7) supporting the inner barrel section 120 (FIG.","7).","For example, the drilling unit bases 212 of the robotic drilling units 208 may be mounted to the system base 202 and may be located inside the inner barrel section 120 as shown in FIG.","7.Alternatively, the drilling unit bases 212 may be located outside of the inner barrel section 120 and the drill end effectors 234 (FIG.","7) of the robotic arm assemblies 210 (FIG.","7) may extend inside the inner barrel section 120 to drill the perforations 136 (FIG.","9).","In a further embodiment, the robotic drilling units 208 may supported by a structure (not shown) that is located separate from the system base 202 and separate from the barrel section 120.For example, the drilling unit bases 212 of the robotic drilling units 208 may be mounted to an overhead fixture (not shown) that may be indexed to the system base 202 and/or to the fixtures 204 supporting the inner barrel section 120.The drill end effectors 234 may extend inside the barrel section 120 to drill the perforations 136.Step 308 of the method 300 of FIG.","13 may include acoustically treating the engine inlet 114 (FIG.","9) by robotically drilling a plurality of perforations 136 (FIG.","9) into the inner face sheet 134 (FIG.","9) of the composite sandwich structure 122 (FIG.","9) engine inlet 114 inner barrel section 120 (FIG.","9) such as after final cure of the composite sandwich structure 122.For example, the method 300 may include robotically drilling the plurality of perforations 136 in the inner barrel section 120 using a plurality of the robotic drilling units 208 (FIG.","9).","The method 300 may include simultaneously drilling the plurality of perforations 136 in the inner face sheet 134 using the drill end effectors 234 (FIG.","9) to provide a predetermined percent-open-area 144 of the inner face sheet 134.In an embodiment, each one of the robotic drilling units 208 may include a robotic arm assembly 210 (FIG.","9) configured as a three-axis, four-axis, five-axis, or six-axis arm assembly respectively having three axes, four axe, five axes, and six axes.","The robotic arm assemblies 210 may be programmed to move the drill end effectors 234 in a synchronized manner relative to one another to drill the perforations 136 at a relatively rapid rate.","For example, each one of the drill end effectors 234 may be configured to form 2-3 or more perforations 136 per second.","The method 300 (FIG.","13) may include drilling the perforations 136 (FIG.","9) in a predetermined hole pattern 140 (FIG.","9) in the engine inlet 114 (FIG.","9) inner barrel section 120 (FIG.","9) which may have a honeycomb core 128 (FIG.","11).","The robotic drilling units 208 (FIG.","9) may be configured to control the drill end effectors 234 (FIG.","9) to drill the perforations 136 normal (e.g., perpendicular) to the inner face sheet 134 (FIG.","10).","In addition, the robotic drilling units 208 may be configured to drill the perforations 136 at a spaced distance to the cell walls 131 (FIG.","11) of the honeycomb core 128.In this regard, the robotic drilling units 208 may be configured to drill one or more perforations 136 in each of the cells 130 at a distance from the cell walls 131 to avoid drilling into the cell walls 131.The robotic drilling units 208 may drill the perforations 136 in a hole pattern 140 that may be configured complementary to the geometry and size of the cells 130 of honeycomb core 128.For example, the hole pattern 140 (FIG.","9) may be such that one perforation 136 (FIG.","11) is drilled into each cell 130 (FIG.","11) such as at an approximate center (not shown) of each cell 130.However, the hole pattern 140 may be such that two or more perforations 136 may be drilled into each cell 130 of the honeycomb core 128 (FIG.","11).","The robotic drilling units 208 (FIG.","9) may be configured to index or position the hole pattern 140 (FIG.","9) relative to the cell 130 (FIG.","11) centers (not shown) or relative to the cell walls 131 (FIG.","11) of a honeycomb core 128.For example, for a honeycomb core 128 having a generally uniform arrangement of cells 130 of equal size and shape, the robotic drilling units 208 may be configured to establish a location of one of the cell walls 13 in order to index a hole pattern 140 relative to the locations of the cell 130 of the honeycomb core 128.After establishing the location of one or more cell walls 131, the robotic drilling units 208 may be configured to drill the hole pattern 140 of perforations 136 in the inner face sheet 134 of the honeycomb core 128 such that each perforation 136 is drilled at a predetermined location in each cell 130 such as at a center (not shown) of each cell 130, or at a predetermined location or spaced distance 146 relative to the cell walls 131 of each cell 130.The hole pattern 140 may also be such that multiple perforations 136 may be drilled into each cell 130 and may be located at predetermined distances or spaced distances 146 from the cell walls 131 of each cell 130.Advantageously, the robotic drilling units 208 (FIG.","9) may be configured to form perforations 136 (FIG.","9) within a relatively high positional tolerance (e.g., 0.010 inch on centers) in the hole-to-hole spacing.","In addition, as indicated above, each one of the drill end effectors 234 (FIG.","10) may include a vacuum attachment 240 (FIG.","10) configured to be positioned adjacent to or against the inner face sheet 134 during the drilling of the perforations 136.The vacuum attachment 240 may include a vacuum port 242 (FIG.","11) that may be coupled to a vacuum source (not shown) via a vacuum hose (not shown) to provide a vacuum 244 (FIG.","10) for suctioning dust, chips, and other debris away from a location where a perforation 136 is being drilled.","Step 310 of the method 300 of FIG.","13 may include periodically changing the drill bits 236 (FIG.","10) of the drill end effectors 234 (FIG.","10) during the process of drilling perforations 136 (FIG.","10) in the inner barrel section 120 (FIG.","10).","In an embodiment, the method may include robotically changing the drill bits 236 using an automated bit changer (not shown).","Drill bits 236 may be replaced after drilling a predetermined quantity of perforations 136.For example, each drill bit 236 may be replaced after drilling several thousand or more perforations 136.The frequency at which the drill bits 236 may be replaced may be affected by the thickness of the inner face sheet 134 (FIG.","11), the material composition of the inner face sheet 134, the rotational speed of the drill bit 236, the feed rate of the drill bit 236, the material composition of the drill bit 236, and other factors.","In an embodiment not shown, the method may include detecting when a drill bit 236 is becoming dull, at which point the method may include replacing the dull drill bit 236 with a new or sharpened drill bit (not shown).","Advantageously, the drilling system 200 (FIG.","12) and method disclosed herein provides for operating a plurality of robotic drilling units 208 (FIG.","12) in a synchronized manner to accurately and rapidly form perforations 136 (FIG.","12) in the inner face sheet 134 (FIG.","12) of an inner barrel section 120 (FIG.","12) with a high degree of repeatability.","In addition, the drilling system 200 provides a means for forming perforations 136 with a significant reduction in defects and rework commonly associated with conventional methods.","In this regard, the drilling system 200 and method disclosed herein may avoid the above-mentioned defects of missing perforations (not shown) and/or blocked perforations (not shown) during subsequent processing in a multi-stage barrel section fabrication process (not shown), and the associated reduction in percent-open-area 144 (FIG.","9) in the inner face sheet 134 of the inner barrel section 120.As indicated above, the percent-open-area 144 (FIG.","9) of the inner face sheet 134 is the total area of the perforations 136 (FIG.","9) as a percentage of the surface area (not shown) of the inner face sheet 134 (FIG.","9) and is a characteristic for measuring the overall effectiveness or acoustic-attenuating capability of the inner barrel section 120 (FIG.","9).","In FIG.","9, the robotic drilling units 208 (FIG.","9) may be operated in a manner to drill perforations 136 to provide a percent-open-area 144 (FIG.","9) in one section 148 (FIG.","9) of the inner face sheet 134 that is different than the percent-open-area 144 in another section 150 (FIG.","9) of the face sheet 134.For example, in FIG.","9, a first section 148 of perforations 136 drilled in the inner face sheet 134 may have a larger percent-open-area 144 relative to a second section 150 of perforations 136 which may be located adjacent to a forward edge 124 and/or an aft edge 126 of the barrel section 120.However, as indicated above, differing sections (not shown) of percent-open-area 144 may be arranged in any manner along the inner face sheet 134 of the inner barrel section 120 (FIG.","9), and are not limited to the arrangement shown in FIG.","9 or described above.","Referring to FIGS.","14-15, embodiments of the disclosure may be described in the context of an aircraft manufacturing and service method 400 as shown in FIG.","14 and an aircraft 402 as shown in FIG.","15.During pre-production, exemplary method 400 may include specification and design 404 of the aircraft 402 and material procurement 406.During production, component and subassembly manufacturing 408 and system integration 410 of the aircraft 402 takes place.","Thereafter, the aircraft 402 may go through certification and delivery 412 in order to be placed in service 414.While in service by a customer, the aircraft 402 is scheduled for routine maintenance and service 416 (which may also include modification, reconfiguration, refurbishment, and so on).","Each of the processes of method 400 may be performed or carried out by a system integrator, a third party, and/or an operator (e.g., a customer).","For the purposes of this description, a system integrator may include without limitation any number of aircraft manufacturers and major-system subcontractors; a third party may include without limitation any number of venders, subcontractors, and suppliers; and an operator may be an airline, leasing company, military entity, service organization, and so on.","As shown in FIG.","15, the aircraft 402 produced by exemplary method 400 may include an airframe 418 with a plurality of systems 420 and an interior 422.Examples of high-level systems 420 include one or more of a propulsion system 424, an electrical system 426, a hydraulic system 428, and an environmental system 430.Any number of other systems may be included.","Although an aerospace example is shown, the principles of the invention may be applied to other industries, such as the automotive industry.","Apparatus and methods embodied herein may be employed during any one or more of the stages of the production and service method 400.For example, components or subassemblies corresponding to production process 408 may be fabricated or manufactured in a manner similar to components or subassemblies produced while the aircraft 402 is in service.","Also, one or more apparatus embodiments, method embodiments, or a combination thereof may be utilized during the production stages 408 and 410, for example, by substantially expediting assembly of or reducing the cost of an aircraft 402.Similarly, one or more of apparatus embodiments, method embodiments, or a combination thereof may be utilized while the aircraft 402 is in service, for example and without limitation, to maintenance and service 416.Many modifications and other embodiments of the disclosure will come to mind to one skilled in the art to which this disclosure pertains having the benefit of the teachings presented in the foregoing descriptions and the associated drawings.","The embodiments described herein are meant to be illustrative and are not intended to be limiting or exhaustive.","Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation."]],"string":"[\n [\n \"SYSTEMS AND METHODS FOR FORMING PERFORATIONS IN A BARREL STRUCTURE\",\n \"A drilling system includes a single robotic drilling unit having a drill end effector positioned inside a barrel section configured as a composite sandwich structure having an inner face sheet.\",\n \"The robotic drilling unit is operable to drill a plurality of perforations into the inner face sheet using the drill end effector.\",\n \"The robotic drilling unit is configured to index a hole pattern of the perforations to one or more cell walls of a honeycomb core of the composite sandwich structure.\",\n \"The robotic drilling unit is configured to form the hole pattern in the inner face sheet such that the perforations are located at a spaced distance from the cell walls of the honeycomb core.\"\n ],\n [\n \"1.A drilling system, comprising: a single robotic drilling unit having a drill end effector positioned inside a barrel section configured as a composite sandwich structure having an inner face sheet; the robotic drilling unit being operable to drill a plurality of perforations into the inner face sheet using the drill end effector; the robotic drilling unit is configured to index a hole pattern of the perforations to one or more cell walls of a honeycomb core of the composite sandwich structure; and the robotic drilling unit is configured to form the hole pattern in the inner face sheet such that the perforations are located at a spaced distance from the cell walls of the honeycomb core.\",\n \"2.The drilling system of claim 1, wherein: the drill end effector is positioned inside a one-piece engine inlet inner barrel section cured in a single stage.\",\n \"3.The drilling system of claim 1, wherein: the robotic drilling unit is operated in a manner to drill the perforations such that a percent-open-area in one section of the inner face sheet is different than the percent-open-area in another section of the inner face sheet.\",\n \"4.The drilling system of claim 1, wherein: the robotic drilling unit has a robotic arm assembly being movable about at least five axes.\",\n \"5.The drilling system of claim 1, wherein: the robotic drilling unit has a drilling unit base positioned inside the barrel section.\",\n \"6.A method of fabricating an engine inlet, comprising the steps of: providing an engine inlet inner barrel section configured as a composite sandwich structure having an inner face sheet; drilling, using a single robotic drilling unit, a plurality of perforations in the inner face sheet after final cure of the composite sandwich structure, wherein the drilling comprises indexing a hole pattern of the perforations to one or more cell walls of a honeycomb core of the composite sandwich structure, and positioning the hole pattern such that each perforation is located at a spaced distance from the cell walls; and forming the plurality of perforations in a quantity providing a predetermined percent-open-area of the inner face sheet.\",\n \"7.The method of claim 6, wherein the step of providing the engine inlet inner barrel section comprises: providing the engine inlet inner barrel section as a one-piece composite sandwich structure.\",\n \"8.The method of claim 6, wherein the step of drilling the plurality of perforations comprises: drilling the perforations to provide a percent-open-area in one section of the inner face sheet that is different than the percent-open-area in another section of the inner face sheet.\",\n \"9.The method of claim 6, further comprising: positioning a drilling unit base of the robotic drilling unit inside the engine inlet inner barrel section prior to drilling the plurality of perforations.\",\n \"10.The method of claim 6, further comprising: indexing the engine inlet inner barrel section and the robotic drilling unit to at least one fixture supporting the barrel section prior to drilling the plurality of perforations.\",\n \"11.A drilling system, comprising: a single robotic drilling unit having a drill end effector positionable inside a barrel structure supported on a system base; the robotic drilling unit being operable to drill a hole pattern of perforations into an inner surface of the barrel structure using the drill end effector; and the robotic drilling unit is configured to index the perforations relative to internal structure of the barrel structure.\",\n \"12.The drilling system of claim 11, wherein: the drill end effector is controlled to drill perforations in a vertical row along a height of the barrel structure and/or in a horizontal row along a circumference of the barrel structure.\",\n \"13.The drilling system of claim 12, wherein: the robotic drilling unit has a vertical base axis; and the drill end effector is rotatable about the vertical base axis to allow the drill end effector to drill another vertical row of perforations adjacent to a previously-drilled vertical row of perforations.\",\n \"14.The drilling system of claim 11, wherein: the robotic drilling unit is suspended over the barrel structure by an overhead fixture during drilling of the perforations.\",\n \"15.The drilling system of claim 11, wherein: the barrel structure comprises multiple segments assembled together to form a closed shape.\",\n \"16.A method of drilling perforations in a barrel structure, comprising the steps of: supporting a barrel structure on a system base; drilling, using a robotic drilling unit having a drill end effector positionable inside the barrel structure, a plurality of perforations into an inner surface of the barrel structure using the drill end effector; and indexing, using the robotic drilling unit, the perforations relative to internal structure of the barrel structure.\",\n \"17.The method of claim 16, wherein the step of drilling the plurality of perforations comprises: drilling, using the drill end effector, the perforations in a vertical row along a height of the barrel structure and/or in a horizontal row along a circumference of the barrel structure.\",\n \"18.The method of claim 17, wherein the step of drilling the plurality of perforations comprises: rotating the drill end effector about vertical base axis of the robotic drilling unit to drill another vertical row of perforations adjacent to a previously-drilled vertical row of perforations.\",\n \"19.The method of claim 16, wherein the step of drilling the plurality of perforations comprises: suspending the robotic drilling unit over the barrel structure by an overhead fixture when drilling the perforations.\",\n \"20.The method of claim 16, further comprising: positioning a drilling unit base of the robotic drilling unit inside the barrel structure prior to drilling the plurality of perforations.\"\n ],\n [\n \" BACKGROUND Commercial airliners are required to meet certain noise standards such as during takeoff and landing.\",\n \"A large portion of the noise produced by a commercial airliner during takeoff and landing is generated by gas turbine engines commonly used on airliners.\",\n \"Known methods for reducing the noise level of a gas turbine engine include acoustically treating the engine inlet of the engine nacelle.\",\n \"In this regard, the inner barrel section of a gas turbine engine inlet may be provided with a plurality of relatively small perforations formed in the walls of the inner barrel section.\",\n \"The perforations absorb some of the noise that is generated by fan blades rotating at high speed at the engine inlet, and thereby reduce the overall noise output of the gas turbine engine.\",\n \"Conventional methods for forming perforations in acoustic structures such as the barrel section include forming the inner wall of the barrel section as a separate component, followed by forming the perforations in the inner wall.\",\n \"The inner wall may then be assembled with other components that make up the barrel section, which is then assembled with the nacelle of the gas turbine engine.\",\n \"Unfortunately, such conventional methods for forming acoustic structures include operations that may result in the blockage of some of the perforations after the perforations have been formed.\",\n \"Conventional methods for forming acoustic structures may also result in missing perforations.\",\n \"Such blocked perforations or missing perforations may reduce the percent-open-area (POA) of the inner wall (e.g., the total area of the perforations as a percentage of the surface area of the inner wall) which is a characteristic of acoustic structures for measuring their overall effectiveness in absorbing or attenuating noise.\",\n \"Furthermore, conventional methods of forming perforations in acoustic structures are time-consuming processes that add to the production schedule and cost.\",\n \"As can be seen, there exists a need in the art for a system and method for forming perforations in an acoustic structure which minimizes or eliminates the occurrence of blocked or missing perforations, and which may be performed in a timely and cost-effective manner.\"\n ],\n [\n \" SUMMARY The above-noted needs associated with forming perforations in an acoustic structure such as an engine inlet are specifically addressed and alleviated by the present disclosure which provides a drilling system that may include a plurality of robotic drilling units.\",\n \"Each one of the robotic drilling units may include a drill end effector positioned inside a barrel section of an engine inlet.\",\n \"The barrel section may be configured as a composite sandwich structure having an inner face sheet.\",\n \"The robotic drilling units may be operable in synchronized movement with one another to drill a plurality of perforations into the inner face sheet using the drill end effectors in a manner providing a predetermined percent-open-area of the inner face sheet.\",\n \"Also disclosed is a method of fabricating an engine inlet.\",\n \"The method may include providing an engine inlet inner barrel section configured as a composite sandwich structure having an inner face sheet, a core, and an outer face sheet.\",\n \"The method may further include robotically drilling a plurality of perforations in the inner face sheet after final cure of the composite sandwich structure.\",\n \"The method may additionally include forming the plurality of perforations in a quantity providing a predetermined percent-open-area of the inner face sheet.\",\n \"In a further embodiment, disclosed is a method of fabricating an engine inlet including the step of providing an engine inlet inner barrel section configured as a one-piece composite sandwich structure having an inner face sheet, an outer face sheet, and a honeycomb core.\",\n \"The composite sandwich structure may be formed in a single stage cure wherein the inner face sheet, the core, and the outer face sheet may be co-cured and/or co-bonded in a single operation.\",\n \"The method may include drilling, using a plurality of robotic drilling units, a plurality of perforations in the inner face sheet after final cure of the composite sandwich structure.\",\n \"The method may further include operating the plurality of robotic drilling units in synchronized movement with one another to simultaneously drill the plurality of perforations.\",\n \"The method may also include forming the plurality of perforations in a quantity providing a predetermined percent-open-area of the inner face sheet.\",\n \"The features, functions and advantages that have been discussed can be achieved independently in various embodiments of the present disclosure or may be combined in yet other embodiments, further details of which can be seen with reference to the following description and drawings below.\"\n ],\n [\n \"CROSS-REFERENCE TO RELATED APPLICATIONS The present application is a continuation application of and claims priority to pending U.S. application Ser.\",\n \"No.\",\n \"15/155,018 filed on May 15, 2016, and entitled SYSTEM FOR FORMING PERFORATIONS IN A BARREL SECTION, which is a divisional application of and claims priority to U.S. application Ser.\",\n \"No.\",\n \"14/012,243 filed on Aug. 28, 2013, now U.S. Pat.\",\n \"No.\",\n \"9,370,827, issued on Jun.\",\n \"21, 2016, and entitled SYSTEM AND METHOD FOR FORMING PERFORATIONS IN A BARREL SECTION, the entire contents of which is expressly incorporated by reference herein.\",\n \"FIELD The present disclosure relates generally to production of acoustic treatment of structures and, more particularly, to the forming of acoustic perforations in an engine inlet barrel section.\",\n \"BACKGROUND Commercial airliners are required to meet certain noise standards such as during takeoff and landing.\",\n \"A large portion of the noise produced by a commercial airliner during takeoff and landing is generated by gas turbine engines commonly used on airliners.\",\n \"Known methods for reducing the noise level of a gas turbine engine include acoustically treating the engine inlet of the engine nacelle.\",\n \"In this regard, the inner barrel section of a gas turbine engine inlet may be provided with a plurality of relatively small perforations formed in the walls of the inner barrel section.\",\n \"The perforations absorb some of the noise that is generated by fan blades rotating at high speed at the engine inlet, and thereby reduce the overall noise output of the gas turbine engine.\",\n \"Conventional methods for forming perforations in acoustic structures such as the barrel section include forming the inner wall of the barrel section as a separate component, followed by forming the perforations in the inner wall.\",\n \"The inner wall may then be assembled with other components that make up the barrel section, which is then assembled with the nacelle of the gas turbine engine.\",\n \"Unfortunately, such conventional methods for forming acoustic structures include operations that may result in the blockage of some of the perforations after the perforations have been formed.\",\n \"Conventional methods for forming acoustic structures may also result in missing perforations.\",\n \"Such blocked perforations or missing perforations may reduce the percent-open-area (POA) of the inner wall (e.g., the total area of the perforations as a percentage of the surface area of the inner wall) which is a characteristic of acoustic structures for measuring their overall effectiveness in absorbing or attenuating noise.\",\n \"Furthermore, conventional methods of forming perforations in acoustic structures are time-consuming processes that add to the production schedule and cost.\",\n \"As can be seen, there exists a need in the art for a system and method for forming perforations in an acoustic structure which minimizes or eliminates the occurrence of blocked or missing perforations, and which may be performed in a timely and cost-effective manner.\",\n \"SUMMARY The above-noted needs associated with forming perforations in an acoustic structure such as an engine inlet are specifically addressed and alleviated by the present disclosure which provides a drilling system that may include a plurality of robotic drilling units.\",\n \"Each one of the robotic drilling units may include a drill end effector positioned inside a barrel section of an engine inlet.\",\n \"The barrel section may be configured as a composite sandwich structure having an inner face sheet.\",\n \"The robotic drilling units may be operable in synchronized movement with one another to drill a plurality of perforations into the inner face sheet using the drill end effectors in a manner providing a predetermined percent-open-area of the inner face sheet.\",\n \"Also disclosed is a method of fabricating an engine inlet.\",\n \"The method may include providing an engine inlet inner barrel section configured as a composite sandwich structure having an inner face sheet, a core, and an outer face sheet.\",\n \"The method may further include robotically drilling a plurality of perforations in the inner face sheet after final cure of the composite sandwich structure.\",\n \"The method may additionally include forming the plurality of perforations in a quantity providing a predetermined percent-open-area of the inner face sheet.\",\n \"In a further embodiment, disclosed is a method of fabricating an engine inlet including the step of providing an engine inlet inner barrel section configured as a one-piece composite sandwich structure having an inner face sheet, an outer face sheet, and a honeycomb core.\",\n \"The composite sandwich structure may be formed in a single stage cure wherein the inner face sheet, the core, and the outer face sheet may be co-cured and/or co-bonded in a single operation.\",\n \"The method may include drilling, using a plurality of robotic drilling units, a plurality of perforations in the inner face sheet after final cure of the composite sandwich structure.\",\n \"The method may further include operating the plurality of robotic drilling units in synchronized movement with one another to simultaneously drill the plurality of perforations.\",\n \"The method may also include forming the plurality of perforations in a quantity providing a predetermined percent-open-area of the inner face sheet.\",\n \"The features, functions and advantages that have been discussed can be achieved independently in various embodiments of the present disclosure or may be combined in yet other embodiments, further details of which can be seen with reference to the following description and drawings below.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS These and other features of the present disclosure will become more apparent upon reference to the drawings wherein like numbers refer to like parts throughout and wherein: FIG.\",\n \"1 is a perspective illustration of an aircraft; FIG.\",\n \"2 is a perspective illustration of a nacelle of a gas turbine engine of the aircraft of FIG.\",\n \"1; FIG.\",\n \"3 is a perspective illustration of an inner barrel section of an engine inlet of the gas turbine engine of FIG.\",\n \"2; FIG.\",\n \"4 is a cross-sectional illustration of a leading edge of the engine inlet of the gas turbine engine of FIG.\",\n \"2; FIG.\",\n \"5 is a perspective illustration of an embodiment of a drilling system for forming perforations in a barrel section; FIG.\",\n \"6 is a perspective illustration of the drilling system with the barrel section shown in phantom lines to illustrate a plurality of robotic drilling units of the drilling system; FIG.\",\n \"7 is a side view of the drilling system; FIG.\",\n \"8 is the top view of the drilling system; FIG.\",\n \"9 is a side view of one of the robotic drilling units forming a hole pattern along an inner face sheet of the inner barrel section; FIG.\",\n \"10 is a perspective illustration of a drill end effector forming a perforation in an inner face sheet of a composite sandwich structure of the inner barrel section; FIG.\",\n \"11 is a cross sectional illustration taken along line 11 of FIG.\",\n \"10 and illustrating a drill bit of the drill end effector drilling a perforation in the inner face sheet of the composite sandwich structure; FIG.\",\n \"12 is a block diagram of an embodiment of the drilling system; FIG.\",\n \"13 is an illustration of a flow chart including one or more operations that may be implemented in a method of fabricating an engine inlet; FIG.\",\n \"14 is a flow diagram of an aircraft manufacturing and service methodology; and FIG.\",\n \"15 is a block diagram of an aircraft.\",\n \"DETAILED DESCRIPTION Referring now to the drawings wherein the showings are for purposes of illustrating various embodiments of the present disclosure, shown in FIG.\",\n \"1 is a perspective illustration of an aircraft 100.The aircraft 100 may include a fuselage 102 extending from a nose to an empennage 104.The empennage 104 may include one or more tail surfaces for directional control of the aircraft 100.The aircraft 100 may include a pair of wings 106 extending outwardly from the fuselage 102.In FIG.\",\n \"1, the aircraft 100 may include one or more propulsion units which, in an embodiment, may be supported by the wings 106.Each one of the propulsion units may be configured as a gas turbine engine 108 having a core engine (not shown) surrounded by a nacelle 110.The nacelle 110 may include an engine inlet 114 and a fan cowl 118 surrounding one or more fans (not shown) mounted on a forward end (not shown) of the core engine.\",\n \"The nacelle 110 may have an exhaust nozzle 112 (e.g., a primary exhaust nozzle and a fan nozzle) at an aft end (not shown) of the gas turbine engine 108.FIG.\",\n \"2 illustrates an embodiment of a gas turbine engine 108 having an engine inlet 114.The engine inlet 114 may include a leading edge 116 and an inner barrel section 120 located aft of the leading edge 116 of the engine inlet 114.The inner barrel section 120 may provide a boundary surface or wall for directing airflow (not shown) entering the engine inlet 114 and passing through the gas turbine engine 108.The inner barrel section 120 may be located in relatively close proximity to one or more fans (not shown).\",\n \"In this regard, the inner barrel section 120 may also be configured to serve as an acoustic structure having a plurality of perforations 136 (FIG.\",\n \"9) in an inner face sheet 134 (FIG.\",\n \"10) of the inner barrel section 120 for absorbing noise generated by the rotating fans and/or noise generated by the airflow entering the engine inlet 114 and passing through the gas turbine engine 108.As described below, the total area of the perforations 136 in the inner face sheet 134 may be expressed as percent-open-area 144 (FIG.\",\n \"9) which represents the total area of the perforations 136 as a percentage of the surface area of the inner face sheet 134.The percent-open-area 141 may be a characteristic for measuring the overall effectiveness or acoustic-attenuating capability of the inner barrel section 120.During the design and/or development of the aircraft 100, a specific, a predetermined percent-open-area 144 (FIG.\",\n \"9) may be selected for the inner barrel section 120 to meet acoustic performance requirements of the engine inlet 114.FIG.\",\n \"3 is a perspective illustration of an embodiment of an inner barrel section 120 of an engine inlet 114.In the embodiment shown, the barrel section 120 may have a diameter (not shown) of up to 5-8 feet or larger, and a length (not shown) extending from an aft edge 126 to a forward edge 124 of up to 2-3 feet or longer.\",\n \"However, the barrel section 120 may be provided in any size, shape, and configuration, without limitation.\",\n \"The inner barrel section 120 may be formed as a composite sandwich structure 122 having an inner face sheet 134 and an outer face sheet 132 separated by a core 128.The inner face sheet 134 and/or the outer face sheet 132 may be formed of composite material including fiber-reinforced polymeric matrix material such as graphite-epoxy, fiberglass-epoxy, or other composite material.\",\n \"Alternatively, the inner face sheet 134 and/or the outer face sheet 132 may be formed of metallic material such as titanium, steel, or other metallic materials or combinations of materials.\",\n \"The core 128 may comprise honeycomb core having a plurality of cells 130 oriented generally transverse to the inner face sheet 134 and outer face sheet 132.The core 128 may be formed of metallic material and/or non-metallic material and may include aluminum, titanium, aramid, fiberglass, or other core materials.\",\n \"In FIG.\",\n \"3, in an embodiment, the engine inlet 114 may comprise a one-piece engine inlet 114 inner barrel section 120.The inner barrel section 120 may be fabricated from raw materials (not shown) and assembled and cured in one or more stages.\",\n \"For example, the inner face sheet 134 and the outer face sheet 132 may be separately formed by laying up dry fiber fabric (not shown) or resin-impregnated ply material (i.e., pre-preg) on separate layup mandrels (not shown) and separately cured, followed by bonding the inner face sheet 134 and the outer face sheet 132 to the core 128.Alternatively, the inner barrel section 120 may be fabricated in a single-stage cure process wherein the inner face sheet 134 may be laid up on a layup mandrel (not shown), after which the core 128 may be laid up over the inner face sheet 134, followed by laying up the outer face sheet 132 over the core 128.The layup assembly (not shown) may be cured in a single stage, after which the drilling system 200 (FIG.\",\n \"5) disclosed herein may be implemented for forming perforations 136 (FIG.\",\n \"9) in the inner face sheet 134.In an embodiment described in greater detail below, the drilling system 200 (FIG.\",\n \"5) disclosed herein may be implemented for forming a plurality of perforations 136 (FIG.\",\n \"9) in the inner face sheet 134 (FIG.\",\n \"9) of the assembled barrel section 120.For example, the drilling system 200 (FIG.\",\n \"5) disclosed herein may include a plurality of robotic drilling units 208 (FIG.\",\n \"8) positioned inside the barrel section 120 for robotically drilling a plurality of the perforations 136 in the inner face sheet 134 after final cure of the composite sandwich structure 122 engine inlet inner barrel section 120.The perforations 136 (FIG.\",\n \"9) may be formed in a size and quantity to provide a predetermined percent-open-area 144 for the inner barrel section 120 to allow the inner barrel section 120 to meet acoustic performance requirements of the engine inlet 114.In FIG.\",\n \"3, the inner barrel section 120 may comprise a unitary structure having closed shape with a generally cylindrical configuration.\",\n \"However, in an embodiment, the inner barrel section 120 may be formed as multiple segments (not shown) assembled together to form a closed shape.\",\n \"The inner barrel section 120 may be provided in a contoured cross-sectional shape (not shown) to promote airflow (not shown) through the gas turbine engine 108.In this regard, when viewed along a circumferential direction, the inner barrel section 120 may have a cross section that may be complexly curved and may be formed complementary to the shape of the engine inlet 114 leading edge 116 at a forward edge 124 of the inner barrel section 120, and complementary to the shape of the interior nacelle surfaces (not shown) aft of the inner barrel section 120.However, the inner barrel section 120 may be provided in any shape including a simple cylindrical shape and/or a conical shape.\",\n \"FIG.\",\n \"4 is a cross-sectional illustration of the leading edge 116 of the engine inlet 114 showing the composite sandwich construction including the circumferential inner face sheet 134, the circumferential outer face sheet 132, and the core 128 separating the inner face sheet 134 and outer face sheet 132 of the barrel section 120.The forward edge 124 of the inner barrel section 120 may be coupled to or may interface with the engine inlet 114 leading edge 116.The aft edge 126 of the inner barrel section 120 may be coupled to or may interface with the nacelle interior (not shown).\",\n \"In the embodiment shown, the inner face sheet 134, the core 128, and the outer face sheet 132 have a complexly-curved cross sectional shape to promote efficient airflow through the nacelle 110.FIG.\",\n \"5 is an illustration of an embodiment of a drilling system 200 as may be implemented for forming perforations 136 (FIG.\",\n \"9) in a barrel section 120 such as the inner barrel section 120 of an engine inlet 114 of a gas turbine engine 108 (FIG.\",\n \"3).\",\n \"However, the drilling system 200 disclosed herein may be implemented for forming perforations 136 (FIG.\",\n \"9) in any type of barrel structure for any application, without limitation.\",\n \"For example, the drilling system 200 may be implemented for forming perforations 136 (FIG.\",\n \"9) in a barrel section of any one of a variety of different types of commercial, civilian, and military aircraft 100 (FIG.\",\n \"1).\",\n \"Furthermore, the drilling system 200 may be implemented for forming perforations 136 (FIG.\",\n \"9) in the barrel section 120 of a gas turbine engine 108 (FIG.\",\n \"1) of rotorcraft, hovercraft, or in any other vehicular or non-vehicular application wherein a predetermined quantity of acoustic perforations 136 (FIG.\",\n \"9) are required in a barrel section 120 for acoustic attenuating purposes.\",\n \"In FIG.\",\n \"5, the drilling system 200 is shown mounted within an interior of a barrel section 120.The drilling system 200 may include robotic drilling units 208 that advantageously allow for forming perforations 136 (FIG.\",\n \"9) in a barrel section 120 to provide the predetermined percent-open-area 144 (FIG.\",\n \"9) of the inner face sheet 134 of the barrel section 120.As indicated above, the predetermined percent-open-area 144 may be determined during the design and/or development of the aircraft 100 (FIG.\",\n \"1) to meet acoustic performance requirements of the engine inlet 114.The drilling system 200 disclosed herein advantageously allows for consistently forming perforations 136 in the inner face sheets 134 of composite sandwich structure 122 barrel sections 120 to provide a predetermined percent-open-area 144 (FIG.\",\n \"9) in the inner face sheet 134.In this regard, the drilling system 200 advantageously overcomes the drawbacks associated with conventional methods for forming perforations (not shown) in conventional inner barrel sections (not shown) such as the above-mentioned drawbacks associated with blocked perforations (not shown) due to subsequent processing of a conventional inner barrel section (not shown) in a conventional multi-stage forming process (not shown), and/or due to missing perforations (not shown) during conventional perforating (not shown) of the inner skin (not shown) of a conventional inner barrel section.\",\n \"Such blocked perforations or missing perforations may reduce the predetermined percent-open-area 144 of the inner skin of the conventional inner barrel section which may reduce the acoustic performance of the engine inlet 114.In FIG.\",\n \"5, a plurality of robotic drilling units 208 (e.g., two robotic drilling units 208, three robotic drilling units 208, etc.)\",\n \"may be supported on a system base 202.Each one of the robotic drilling units 208 may include a drill end effector 234.In an embodiment, the system base 202 may comprise a relatively rigid structure and may include a tooling fixture, a shop floor, or a table configured to support the plurality of robotic drilling units 208.In addition, the system base 202 may be configured to support the barrel section 120.However, the drilling system 200 may be provided in an alternative embodiment wherein the plurality of robotic drilling units 208 are supported by a structure that is located separate from the barrel section 120.For example, the plurality of robotic drilling units 208 may be suspended over the inner barrel section 120 such as by an overhead fixture (not shown) in a manner such that the drill end effectors 234 may be positioned within the interior of the barrel section 120, and/or the plurality of robotic drilling units 208 may be mounted inside or outside of the barrel section 120.FIG.\",\n \"6 is a perspective illustration of the plurality of robotic drilling units 208 positioned on the system base 202 and mounted within relatively close proximity to one another such that the barrel section 120 circumscribes the plurality of robotic drilling units 208 when the barrel section 120 is mounted to the system base 202.Although four (4) robotic drilling units 208 are shown, any number may be provided.\",\n \"In an embodiment, the robotic drilling units 208 may be mounted in an array.\",\n \"For example, each one of the robotic drilling units 208 may include a drilling unit base 212 (FIG.\",\n \"7).\",\n \"The drilling unit bases 212 (FIG.\",\n \"7) may be mounted to the system base 202 in a circular array 206 (FIG.\",\n \"8) such that when the barrel section 120 is mounted to the system base 202, each one of the drilling unit bases 212 (FIG.\",\n \"7) is positioned at substantially the same distance from the inner face sheet 134 of the barrel section 120.FIG.\",\n \"7 is a side view of an embodiment of the drilling system 200.The barrel section 120, shown in phantom lines, may be supported on one fixture 204 or multiple fixtures 204.The fixtures 204 may comprise spacers sized and configured to position the barrel section 120 at a vertical location that is complementary to the movement capability of the drill end effectors 234 of the robotic drilling units 208.In this regard, the fixtures 204 may be configured such that the drill end effectors 234 may form perforations 136 (FIG.\",\n \"9) in the inner face sheet 134 of the barrel section 120 at any vertical location between the forward edge 124 of the barrel section 120 and the aft edge 126 of the barrel section 120.The fixtures 204 may be comprised of a rigid material and may be configured as simple blocks (not shown) formed of metallic or polymeric material and which may be fixedly coupled to the system base 202.The fixtures 204 may extend vertically along any portion of the height of the barrel section and horizontally along any portion of the circumference of the barrel section 120.FIG.\",\n \"8 is a top view of the drilling system 200 illustrating an arrangement of the robotic drilling units 208.Each one of the robotic drilling units 208 may include a robotic arm assembly 210 having a drill end effector 234 mounted on an end of the robotic arm assembly 210.The robotic drilling units 208 may be mounted such that drilling unit bases 212 are positioned adjacent to a center of the array of the robotic drilling units 208.In an embodiment, the drilling system 200 may comprise a single robotic drilling unit 208 or a plurality of robotic drilling units 208.For example, the drilling system 200 may include two (2) or more robotic drilling units 208 having drilling unit bases 212 which may be arranged at a predetermined spacing relative to one another, such as a substantially equiangular spacing relative to one another.\",\n \"Referring still to FIG.\",\n \"8, the plurality of robotic drilling units 208 may be configured (e.g., programmed) to drill perforations 136 (FIG.\",\n \"9) within substantially equivalent arc segments 142 of the barrel section 120.For example, for the embodiment shown, the plurality of robotic drilling units 208 may comprise four (4) robotic drilling units 208.The drilling unit bases 212 may be arranged such that the drilling unit bases 212 are positioned at an angular spacing of approximately ninety degrees relative to one another.\",\n \"In an embodiment, each one of the robotic drilling units 208 may be configured to drill perforations 136 (FIG.\",\n \"9) within an approximate ninety-degree arc segment 142 of the barrel section 120.However, the robotic drilling units 208 may be positioned at any location relative to one another and may be configured to form perforations 136 (FIG.\",\n \"9) at any circumstantial location or any vertical location of the barrel section 120.In FIG.\",\n \"8, the drill end effector 234 of each one of the robotic drilling units 208 may be oriented generally radially outwardly away from the drilling unit base 212.The drilling unit bases 212 may be positioned to provide space for movement of the robotic arm assemblies 210 during operation of the drilling system 200.In this regard, the robotic drilling units 208 are simultaneously operable in synchronized movement with one another in a manner allowing the drill end effectors 234 to simultaneously drill a plurality of perforations 136 (FIG.\",\n \"9) in the barrel section 120.The robotic drilling units 208 may be programmed to avoid collisions with one another and with the barrel section 120 during the synchronized movement with one another.\",\n \"FIG.\",\n \"9 is a side view of one of the robotic drilling units 208 showing the barrel section 120 supported on fixtures 204 and illustrating a drill bit 236 of one of the drill end effectors 234 forming perforations 136 in a predetermined hole pattern 140 along the inner face sheet 134 of the inner barrel section 120.In this regard, in an embodiment, each one of the robotic drilling units 208 may be indexed to the system base 202.The barrel section 120 may also be indexed to the system base 202 such as with fixtures 204 to provide a means for the drill end effector 234 to form perforations 136 within a relatively small positional tolerance relative to a circumferential direction (not shown) of the barrel section 120 and relative to an axial direction (not shown) of the barrel section 120.However, the barrel section 120 and the robotic drilling units 208 may be indexed relative to one another by other means, and are not necessarily limited to being indexed to the system base 202.In FIG.\",\n \"9, the robotic drilling units 208 may be operated in a manner to drill the perforations 136 in the inner face sheet 134 such that a percent-open-area 144 in one section 148 of the inner face sheet 134 is different than the percent-open-area 144 in another section 150 of the inner face sheet 134.In this regard, the robotic drilling units 208 may be programmed to drill perforations 136 to provide a greater percent-open-area 144 in a first section 148 of the inner face sheet 134 relative to drilling perforations 136 to provide a lower percent-open-area 144 in a second section 150 of the inner face sheet 134.For example, the second section 150 with a smaller percent-open-area 144 may be located adjacent to a forward edge 124 and/or an aft edge 126 of the barrel section 120, and the first section 148 with a larger percent-open-area 144 may be located in an interior region (not shown) of the inner barrel section 120 between the forward edge 124 and the aft edge 126.However, the robotic drilling 208 units may drill the perforations 136 such that the percent-open-area 144 in the inner face sheet 134 is different at different circumferential sections (not shown) of the barrel section 120, or the percent-open-area 144 of the inner barrel section 120 may vary in a different manner than the above-noted embodiments.\",\n \"In FIG.\",\n \"9, one or more of the robotic drilling units 208 may have a six-axis robotic arm assembly 210 which may allow for accurately positioning the drill end effector 234 at any desired location and orientation along the inner face sheet 134.As the drill end effector 234 is positioned and oriented at a desired location of a perforation 136, the drill end effector 234 may be moved axially to drive the rotating drill bit 236 into the inner face sheet 134 to form a perforation 136.Alternatively, the drill end effector 234 may be positioned at a desired location of a perforation 136 on the inner face sheet 134, and the drill end effector 234 may axially drive the rotating drill bit 236 along a direction of the drill bit axis 238 to drill the perforation 136 in the inner face sheet 134.In an embodiment, the six-axis robotic arm assembly 210 may include a first arm 220 which may be attached to the drilling unit base 212 at a shoulder joint 216.The first arm 220 may be attached to a second arm 226 at an elbow joint 222.The second arm 226 may be attached to the drill end effector 234 at a wrist joint 230.In FIG.\",\n \"9, the drilling unit base 212 may be configured to rotate about a vertical base axis 214 relative to the system base 202.The first arm 220 may be configured to rotate about a shoulder axis 218 of the shoulder joint 216 coupling the first arm 220 to the drilling unit base 212.The second arm 226 may be configured to rotate about an elbow axis 224 of the elbow joint 222 coupling the second arm 226 to the first arm 220.A portion of the second arm 226 may also be configured to swivel about a second arm axis 228 extending along a direction from the elbow joint 222 to the wrist joint 230.The drill end effector 234 may be configured to rotate about a wrist axis 232 of the wrist joint 230.In addition, the drill end effector 234 may be configured to rotate about an end effector axis 235 which may be generally parallel to the drill bit axis 238.In an optional embodiment, the end effector may be configured to linearly translate the drill bit 236 along a drill bit axis 238 such as when drilling a perforation 136 in the inner face sheet 134.In FIG.\",\n \"9, the robotic arm assembly 210 is shown in a six-axis embodiment.\",\n \"However, the robotic arm assembly 210 may be provided in alternative arrangements.\",\n \"For example, the robotic arm assembly 210 may be provided in a 3-axis embodiment (not shown), a 4-axis embodiment (not shown), or a 5-axis embodiment (not shown).\",\n \"In addition, the robotic arm assembly 210 may be provided in an embodiment having more than six (6) axes.\",\n \"Furthermore, the robotic arm assembly 210 may be configured as a motion control system (not shown), a rigid frame (not shown) having linear axes along which the end effector is movable, or any other type of motion control device for controlling a drill end effector 234 for drilling perforations 136.In addition, each robotic arm assembly 210 may include more than one drill end effector 234.Furthermore, each drill end effector 234 may have more than one drill bit 236 for simultaneously forming perforations 136.FIG.\",\n \"10 shows a drill end effector 234 forming a perforation 136 in the inner face sheet 134 of a composite sandwich structure 122 of the inner barrel section 120.Advantageously, the drilling system 200 provides a means for accurate and rapid placement of the drill end effector 234 for drilling perforations 136 in a predetermined hole pattern 140 (FIG.\",\n \"9).\",\n \"For example, in an embodiment, each one of the drill end effectors 234 of a robotic drilling unit 208 may be configured to form up to three (3) or more perforations 136 per second, per drill end effector 234.In an embodiment, the drill end effector 234 may be provided with a drill bit 236 configured to form acoustic perforations 136 having a hole diameter of approximately 0.010 to 0.10 inch, although larger or smaller perforations 136 are possible based on the drill bit 236 diameter.\",\n \"In FIG.\",\n \"10, for forming perforations 136 in a composite inner face sheet 134, the drill end effector 234 may be configured to drive the drill bit 236 at a feed rate of approximately 20-60 inches per minute, and at rotational speeds of between approximately 20,000 to 40,000 rpm, although larger or smaller feed rates and larger or smaller rotational speeds may be selected based on the material being drilled and the composition of the drill bit 236.The drill bit 236 feed rate and the drill bit 236 rotational speed may be controlled to minimize drill bit 236 wear, and such that the perforations 136 may meet tight tolerances for roundness and other hole parameters.\",\n \"Significantly, each robotic drilling unit 208 is configured to quickly and accurately form hole patterns 140 (FIG.\",\n \"9) at a relatively small center-to-center positional tolerance (i.e., perforation-to-perforation) such as a center-to-center positional tolerance of approximately 0.010 inch or less.\",\n \"However, the center-to-center positional tolerance may be greater than 0.010 inch, such as up to approximately 0.050 inch or greater.\",\n \"In FIG.\",\n \"10, one or more of the drill end effectors 234 may include a vacuum attachment 240 for removing debris (not shown) such as dust and chips that may be generated during the drilling of the perforations 136.The vacuum attachment 240 may have a hollow (not shown) or open portion (not shown) that may be positioned around the drill bit 236 and may be placed adjacent to or in contact with the inner face sheet 134 when the drill bit 236 contacts the inner face sheet 134 and drills a perforation 136.The vacuum attachment 240 may include a vacuum port 242 for connection to a vacuum source (not shown) using a vacuum hose (not shown) for drawing a vacuum 244 on the vacuum attachment 240 for drawing debris (not shown) from the area surrounding the perforation 136.In FIG.\",\n \"10, in a further embodiment, the drilling system 200 may be provided with an automated bit changer (not shown) for changing the drill bits 236 using robotic control.\",\n \"In this manner, worn drill bits 236 may be replaced after drilling a predetermined quantity of perforations 136.For example, an automated bit changer (not shown) may replace each drill bit 236 after drilling anywhere from approximately 1,000 to 30,000 perforations 136, although the drill bits 236 may be replaced after drilling a smaller or larger quantity of perforations 136 than the above-noted range.\",\n \"Depending upon the size (e.g., diameter and height) of the inner barrel section 120 and the total quantity of robotic drilling units 208 that are used, each drill end effector 234 may undergo 1 to 20 or more drill bit changes per barrel section 120.Referring briefly to FIG.\",\n \"9, in an embodiment, the drill end effectors 234 may be controlled to drill perforations 136 in a hole pattern 140 of vertical rows (not shown) along a height of the barrel section 120.In this regard, each drill end effector 234 may drill a vertical row of perforations 136, and the drill end effector 234 may be rotated about the vertical base axis 214 to allow the drill end effector 234 to drill another vertical row of perforations 136 adjacent to the previously-drilled vertical row of perforations 136.The drill end effectors 234 may also be controlled to drill perforations 136 in horizontal rows (not shown), or in any other direction or combination of directions.\",\n \"As indicated above, the robotic arm assemblies 210 may be operated in a synchronized manner such that the drill end effectors 234 are maintained at a generally equiangular spacing from one another during the simultaneous drilling of perforations 136 in the inner face sheet 134 of the barrel section 120.For example, for a drilling system 200 having four (4) robotic drilling units 208, the drill end effectors 234 may be maintained at an angular separation of approximately ninety (90) degrees from each other during the simultaneous drilling of perforations 136 in the inner face sheet 134.FIG.\",\n \"11 is a cross sectional view of a drill bit 236 of the drill end effector 234 forming a perforation 136 in the inner face sheet 134 of a composite sandwich structure 122.In an embodiment, the drill end effector 234 may include a drill stop (not shown) to control a depth 138 at which the drill bit 236 extends into the composite sandwich structure 122, and minimize the depth 138 of the drill bit 236 into the core 128 material.\",\n \"Furthermore, a drill stop (not shown) may stabilize the drill end effector 234 when drilling the perforation 136 to prevent lateral movement of the drill bit 236 relative to the perforation 136, and which may advantageously avoid a non-conformance regarding the positional tolerance, roundness tolerance, or other tolerance parameters of the perforation 136.In an embodiment, each drill end effector 234 may include a non-contact method of gauging the depth 138 at which each perforation 136 is drilled such as by using a laser device (not shown), an ultrasonic device (not shown), and other non-contact device.\",\n \"The depth 138 of drilling may also be controlled by a controller (not shown) controlling the drill end effector 234.FIG.\",\n \"12 is a block diagram of an embodiment of a drilling system 200.The drilling system 200 may include a plurality of robotic drilling units 208.Each one of the robotic drilling units 208 may include a robotic arm assembly 210 as described above.\",\n \"A drill end effector 234 may be coupled to the end of each one of the robotic arm assemblies 210 of each robotic drilling unit 208.The robotic drilling units 208 may be simultaneously operable in synchronized movement with one another such that the drill end effectors 234 may simultaneously drill a plurality of perforations 136 in the barrel section 120.In FIG.\",\n \"12, the barrel section 120 may comprise an inner barrel section 120 of an engine inlet 114 such as of a gas turbine engine 108 (FIG.\",\n \"3), as indicated above.\",\n \"In an embodiment, the barrel section 120 may be formed as a composite sandwich structure 122.The composite sandwich structure 122 may have an outer face sheet 132, a core 128, and an inner face sheet 134 which may be assembled or bonded together to form a one-piece engine inlet inner barrel section 120.The drilling system 200 may rapidly and accurately form a plurality of perforations 136 in a predetermined hole pattern of perforations 136 (FIG.\",\n \"9) in the inner face sheet 134 to provide a predetermined percent-open-area 144 for the inner barrel section 120 to meet acoustic performance requirements.\",\n \"FIG.\",\n \"13 is an illustration of a flow chart including one or more operations that may be included in a method 300 of fabricating an engine inlet 114 (FIG.\",\n \"3).\",\n \"Step 302 of the method may include providing a barrel section 120 (FIG.\",\n \"3) such as an inner barrel section 120 (FIG.\",\n \"3) of an engine inlet 114 (FIG.\",\n \"3).\",\n \"As indicated above, the inner barrel section 120 (FIG.\",\n \"3) may be provided as a one-piece composite sandwich structure 122 (FIG.\",\n \"3).\",\n \"In such a composite sandwich structure 122 (FIG.\",\n \"3), the inner face sheet 134 (FIG.\",\n \"3) may be formed of composite material and the outer face sheet 132 (FIG.\",\n \"3) may be formed of composite material (e.g., fiber-reinforced polymeric matrix material).\",\n \"However, the inner face sheet 134 (FIG.\",\n \"3) and/or the outer face sheet 132 (FIG.\",\n \"3) may be formed of metallic material, or a combination of metallic material and non-metallic material.\",\n \"As indicated above, the core 128 (FIG.\",\n \"3) may comprise honeycomb core formed of metallic material and/or non-metallic material and may include aluminum, titanium, aramid, fiberglass, or other core materials.\",\n \"The engine inlet 114 (FIG.\",\n \"3) inner barrel section 120 (FIG.\",\n \"3) may be fabricated as a one-piece composite sandwich structure 122 (FIG.\",\n \"3) formed in a single-stage cure.\",\n \"As described above, the barrel section 120 (FIG.\",\n \"3) may be provided in a single-stage cure wherein the inner face sheet 134 (FIG.\",\n \"3), the core 128 (FIG.\",\n \"3), and the outer face sheet 132 (FIG.\",\n \"3) may be laid up on a layup mandrel, after which heat and/or pressure may be applied to the layup (not shown) for a predetermined time for curing in a single stage.\",\n \"Step 304 of the method 300 of FIG.\",\n \"13 may include mounting and indexing the inner barrel section 120 (FIG.\",\n \"7) to a system base 202 (FIG.\",\n \"7).\",\n \"In this regard, the inner barrel section 120 (FIG.\",\n \"7) may be supported on a plurality of fixtures 204 (FIG.\",\n \"7) which may be mounted to the system base 202 (FIG.\",\n \"7).\",\n \"The fixtures 204 (FIG.\",\n \"7) may fixedly position the inner barrel section 120 (FIG.\",\n \"7) on the system base 202 (FIG.\",\n \"7) which may comprise a table (not shown), an assembly (not shown), or other relatively rigid structure configured to support the inner barrel section 120 (FIG.\",\n \"7) and prevent movement thereof during the drilling of the perforations 136 (FIG.\",\n \"9) in the inner barrel section 120 (FIG.\",\n \"7).\",\n \"As indicated above, the fixtures 204 may be positioned at spaced intervals around a perimeter (not shown) of the inner barrel section 120 such as along the aft edge 126 (FIG.\",\n \"9) or forward edge 124 (FIG.\",\n \"9) of the inner barrel section 120.The fixtures 204 may include mechanical indexing features (not shown) to index the inner barrel section 120 to the fixtures 204.A laser system (not shown) may be implemented to aid in positioning the inner barrel section 120 relative to the fixtures 204.The inner barrel section 120 may be mechanically coupled to the fixtures 204 to rigidly clamp the inner barrel section 120 in position.\",\n \"Step 306 of the method 300 of FIG.\",\n \"13 may include indexing the plurality of robotic drilling units to the system base 202 (FIG.\",\n \"7) as shown in FIG.\",\n \"7.In an embodiment, each one of the plurality of robotic drilling units 208 (FIG.\",\n \"7) may have a drilling unit base 212 (FIG.\",\n \"7) that may be directly mounted to the system base 202 and indexed to the system base 202 and/or to the fixtures 204 (FIG.\",\n \"7) supporting the inner barrel section 120 (FIG.\",\n \"7).\",\n \"For example, the drilling unit bases 212 of the robotic drilling units 208 may be mounted to the system base 202 and may be located inside the inner barrel section 120 as shown in FIG.\",\n \"7.Alternatively, the drilling unit bases 212 may be located outside of the inner barrel section 120 and the drill end effectors 234 (FIG.\",\n \"7) of the robotic arm assemblies 210 (FIG.\",\n \"7) may extend inside the inner barrel section 120 to drill the perforations 136 (FIG.\",\n \"9).\",\n \"In a further embodiment, the robotic drilling units 208 may supported by a structure (not shown) that is located separate from the system base 202 and separate from the barrel section 120.For example, the drilling unit bases 212 of the robotic drilling units 208 may be mounted to an overhead fixture (not shown) that may be indexed to the system base 202 and/or to the fixtures 204 supporting the inner barrel section 120.The drill end effectors 234 may extend inside the barrel section 120 to drill the perforations 136.Step 308 of the method 300 of FIG.\",\n \"13 may include acoustically treating the engine inlet 114 (FIG.\",\n \"9) by robotically drilling a plurality of perforations 136 (FIG.\",\n \"9) into the inner face sheet 134 (FIG.\",\n \"9) of the composite sandwich structure 122 (FIG.\",\n \"9) engine inlet 114 inner barrel section 120 (FIG.\",\n \"9) such as after final cure of the composite sandwich structure 122.For example, the method 300 may include robotically drilling the plurality of perforations 136 in the inner barrel section 120 using a plurality of the robotic drilling units 208 (FIG.\",\n \"9).\",\n \"The method 300 may include simultaneously drilling the plurality of perforations 136 in the inner face sheet 134 using the drill end effectors 234 (FIG.\",\n \"9) to provide a predetermined percent-open-area 144 of the inner face sheet 134.In an embodiment, each one of the robotic drilling units 208 may include a robotic arm assembly 210 (FIG.\",\n \"9) configured as a three-axis, four-axis, five-axis, or six-axis arm assembly respectively having three axes, four axe, five axes, and six axes.\",\n \"The robotic arm assemblies 210 may be programmed to move the drill end effectors 234 in a synchronized manner relative to one another to drill the perforations 136 at a relatively rapid rate.\",\n \"For example, each one of the drill end effectors 234 may be configured to form 2-3 or more perforations 136 per second.\",\n \"The method 300 (FIG.\",\n \"13) may include drilling the perforations 136 (FIG.\",\n \"9) in a predetermined hole pattern 140 (FIG.\",\n \"9) in the engine inlet 114 (FIG.\",\n \"9) inner barrel section 120 (FIG.\",\n \"9) which may have a honeycomb core 128 (FIG.\",\n \"11).\",\n \"The robotic drilling units 208 (FIG.\",\n \"9) may be configured to control the drill end effectors 234 (FIG.\",\n \"9) to drill the perforations 136 normal (e.g., perpendicular) to the inner face sheet 134 (FIG.\",\n \"10).\",\n \"In addition, the robotic drilling units 208 may be configured to drill the perforations 136 at a spaced distance to the cell walls 131 (FIG.\",\n \"11) of the honeycomb core 128.In this regard, the robotic drilling units 208 may be configured to drill one or more perforations 136 in each of the cells 130 at a distance from the cell walls 131 to avoid drilling into the cell walls 131.The robotic drilling units 208 may drill the perforations 136 in a hole pattern 140 that may be configured complementary to the geometry and size of the cells 130 of honeycomb core 128.For example, the hole pattern 140 (FIG.\",\n \"9) may be such that one perforation 136 (FIG.\",\n \"11) is drilled into each cell 130 (FIG.\",\n \"11) such as at an approximate center (not shown) of each cell 130.However, the hole pattern 140 may be such that two or more perforations 136 may be drilled into each cell 130 of the honeycomb core 128 (FIG.\",\n \"11).\",\n \"The robotic drilling units 208 (FIG.\",\n \"9) may be configured to index or position the hole pattern 140 (FIG.\",\n \"9) relative to the cell 130 (FIG.\",\n \"11) centers (not shown) or relative to the cell walls 131 (FIG.\",\n \"11) of a honeycomb core 128.For example, for a honeycomb core 128 having a generally uniform arrangement of cells 130 of equal size and shape, the robotic drilling units 208 may be configured to establish a location of one of the cell walls 13 in order to index a hole pattern 140 relative to the locations of the cell 130 of the honeycomb core 128.After establishing the location of one or more cell walls 131, the robotic drilling units 208 may be configured to drill the hole pattern 140 of perforations 136 in the inner face sheet 134 of the honeycomb core 128 such that each perforation 136 is drilled at a predetermined location in each cell 130 such as at a center (not shown) of each cell 130, or at a predetermined location or spaced distance 146 relative to the cell walls 131 of each cell 130.The hole pattern 140 may also be such that multiple perforations 136 may be drilled into each cell 130 and may be located at predetermined distances or spaced distances 146 from the cell walls 131 of each cell 130.Advantageously, the robotic drilling units 208 (FIG.\",\n \"9) may be configured to form perforations 136 (FIG.\",\n \"9) within a relatively high positional tolerance (e.g., 0.010 inch on centers) in the hole-to-hole spacing.\",\n \"In addition, as indicated above, each one of the drill end effectors 234 (FIG.\",\n \"10) may include a vacuum attachment 240 (FIG.\",\n \"10) configured to be positioned adjacent to or against the inner face sheet 134 during the drilling of the perforations 136.The vacuum attachment 240 may include a vacuum port 242 (FIG.\",\n \"11) that may be coupled to a vacuum source (not shown) via a vacuum hose (not shown) to provide a vacuum 244 (FIG.\",\n \"10) for suctioning dust, chips, and other debris away from a location where a perforation 136 is being drilled.\",\n \"Step 310 of the method 300 of FIG.\",\n \"13 may include periodically changing the drill bits 236 (FIG.\",\n \"10) of the drill end effectors 234 (FIG.\",\n \"10) during the process of drilling perforations 136 (FIG.\",\n \"10) in the inner barrel section 120 (FIG.\",\n \"10).\",\n \"In an embodiment, the method may include robotically changing the drill bits 236 using an automated bit changer (not shown).\",\n \"Drill bits 236 may be replaced after drilling a predetermined quantity of perforations 136.For example, each drill bit 236 may be replaced after drilling several thousand or more perforations 136.The frequency at which the drill bits 236 may be replaced may be affected by the thickness of the inner face sheet 134 (FIG.\",\n \"11), the material composition of the inner face sheet 134, the rotational speed of the drill bit 236, the feed rate of the drill bit 236, the material composition of the drill bit 236, and other factors.\",\n \"In an embodiment not shown, the method may include detecting when a drill bit 236 is becoming dull, at which point the method may include replacing the dull drill bit 236 with a new or sharpened drill bit (not shown).\",\n \"Advantageously, the drilling system 200 (FIG.\",\n \"12) and method disclosed herein provides for operating a plurality of robotic drilling units 208 (FIG.\",\n \"12) in a synchronized manner to accurately and rapidly form perforations 136 (FIG.\",\n \"12) in the inner face sheet 134 (FIG.\",\n \"12) of an inner barrel section 120 (FIG.\",\n \"12) with a high degree of repeatability.\",\n \"In addition, the drilling system 200 provides a means for forming perforations 136 with a significant reduction in defects and rework commonly associated with conventional methods.\",\n \"In this regard, the drilling system 200 and method disclosed herein may avoid the above-mentioned defects of missing perforations (not shown) and/or blocked perforations (not shown) during subsequent processing in a multi-stage barrel section fabrication process (not shown), and the associated reduction in percent-open-area 144 (FIG.\",\n \"9) in the inner face sheet 134 of the inner barrel section 120.As indicated above, the percent-open-area 144 (FIG.\",\n \"9) of the inner face sheet 134 is the total area of the perforations 136 (FIG.\",\n \"9) as a percentage of the surface area (not shown) of the inner face sheet 134 (FIG.\",\n \"9) and is a characteristic for measuring the overall effectiveness or acoustic-attenuating capability of the inner barrel section 120 (FIG.\",\n \"9).\",\n \"In FIG.\",\n \"9, the robotic drilling units 208 (FIG.\",\n \"9) may be operated in a manner to drill perforations 136 to provide a percent-open-area 144 (FIG.\",\n \"9) in one section 148 (FIG.\",\n \"9) of the inner face sheet 134 that is different than the percent-open-area 144 in another section 150 (FIG.\",\n \"9) of the face sheet 134.For example, in FIG.\",\n \"9, a first section 148 of perforations 136 drilled in the inner face sheet 134 may have a larger percent-open-area 144 relative to a second section 150 of perforations 136 which may be located adjacent to a forward edge 124 and/or an aft edge 126 of the barrel section 120.However, as indicated above, differing sections (not shown) of percent-open-area 144 may be arranged in any manner along the inner face sheet 134 of the inner barrel section 120 (FIG.\",\n \"9), and are not limited to the arrangement shown in FIG.\",\n \"9 or described above.\",\n \"Referring to FIGS.\",\n \"14-15, embodiments of the disclosure may be described in the context of an aircraft manufacturing and service method 400 as shown in FIG.\",\n \"14 and an aircraft 402 as shown in FIG.\",\n \"15.During pre-production, exemplary method 400 may include specification and design 404 of the aircraft 402 and material procurement 406.During production, component and subassembly manufacturing 408 and system integration 410 of the aircraft 402 takes place.\",\n \"Thereafter, the aircraft 402 may go through certification and delivery 412 in order to be placed in service 414.While in service by a customer, the aircraft 402 is scheduled for routine maintenance and service 416 (which may also include modification, reconfiguration, refurbishment, and so on).\",\n \"Each of the processes of method 400 may be performed or carried out by a system integrator, a third party, and/or an operator (e.g., a customer).\",\n \"For the purposes of this description, a system integrator may include without limitation any number of aircraft manufacturers and major-system subcontractors; a third party may include without limitation any number of venders, subcontractors, and suppliers; and an operator may be an airline, leasing company, military entity, service organization, and so on.\",\n \"As shown in FIG.\",\n \"15, the aircraft 402 produced by exemplary method 400 may include an airframe 418 with a plurality of systems 420 and an interior 422.Examples of high-level systems 420 include one or more of a propulsion system 424, an electrical system 426, a hydraulic system 428, and an environmental system 430.Any number of other systems may be included.\",\n \"Although an aerospace example is shown, the principles of the invention may be applied to other industries, such as the automotive industry.\",\n \"Apparatus and methods embodied herein may be employed during any one or more of the stages of the production and service method 400.For example, components or subassemblies corresponding to production process 408 may be fabricated or manufactured in a manner similar to components or subassemblies produced while the aircraft 402 is in service.\",\n \"Also, one or more apparatus embodiments, method embodiments, or a combination thereof may be utilized during the production stages 408 and 410, for example, by substantially expediting assembly of or reducing the cost of an aircraft 402.Similarly, one or more of apparatus embodiments, method embodiments, or a combination thereof may be utilized while the aircraft 402 is in service, for example and without limitation, to maintenance and service 416.Many modifications and other embodiments of the disclosure will come to mind to one skilled in the art to which this disclosure pertains having the benefit of the teachings presented in the foregoing descriptions and the associated drawings.\",\n \"The embodiments described herein are meant to be illustrative and are not intended to be limiting or exhaustive.\",\n \"Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation.\"\n ]\n]"},"source":{"kind":"string","value":"Patent_15871958"}}},{"rowIdx":4493965,"cells":{"text":{"kind":"list like","value":[["METHOD FOR IMPROVED TRANSPORT OF MATERIALS THROUGH A PIPE, TUBE OR CYLINDER STRUCTURE USING A VORTEX EFFECT PRODUCTION DEVICE","A tubular or cylindrical unit that creates a vortex effect with externally supplied pressurized fluid injected angularly within a transport structure is provided.","Such a unit is utilized to either accelerate the vacuum and/or air conveyance of liquids, solid aggregates, and gases, reduce the energy required for such materials transport processes, or both.","Such a result is achieved through the introduction of pressurized fluid via a plurality of injectors situated evenly around the circumference of the subject tube, pipe, and/or cylinder, and angled uniformly for an even pressure injection of fluid within the conveyance component thereof.","In effect, through such injection of pressurized fluid, the overall transport system may be operated at significantly reduced cost while increasing the efficiency of overall vacuum and air conveyance systems simultaneously.","The method of utilization of such a device is also encompassed within this invention."],["1.A method of providing materials transport, said method comprising the steps of: a) providing a materials transport device including a cylinder, pipe, and/or tube conveyance component having an external portion and an internal portion, both measuring the same length and sharing the same first end and same opposing second end, wherein said conveyance component comprises at least three injectors substantially evenly spaced circumferentially around said external portion and substantially evenly spaced at differing locations along said length of said external portion, said at least three injectors providing internal introduction of forced fluids angularly within the internal portion of said conveyance component, wherein said injectors are aligned to provide uniform angles of fluid introduction within said conveyance component internal portion, and wherein said uniform angles of fluid introduction create a vortex effect within said conveyance component upon uniform introduction of fluid or gas materials within said injectors such that said vortex effect creates vacuum acceleration in one direction and vacuum deceleration in the reverse direction; b) introducing a material for transport within said transport device and said fluid or gas materials within said at least three injectors; and c) creating a vortex effect within said transport device upon gas or fluid movement from said injectors within said transport device, thereby forcing said material for transport to move within said transport device.","2.The method of providing materials transport of claim 1 wherein said materials transport device further including a fluid source component that is connected separately to each injector, thereby introducing the same pressure and velocity fluid within the conveyance component internal portion during operation.","3.The method of providing materials transport of claim 1 wherein said material transport device is in the form of a solids transport structure, a liquid transport structure, or a gas transport structure.","4.The method of providing materials transport of claim 2 wherein said material transport device is in the form of a solids transport structure, a liquid transport structure, or a gas transport structure.","5.The method of providing materials transport of claim 1 wherein said material transport device is provided in the form of a valve-like structure, a vacuum-assisted structure, or an air or liquid conveyance structure.","6.The method of providing materials transport of claim 2 wherein said material transport device is provided in the form of a valve-like structure, a vacuum-assisted structure, or an air or liquid conveyance structure."],[" BACKGROUND OF THE INVENTION Transport of materials, whether liquids, solids, and even gases, has been of enormous importance for a myriad of reasons.","Whether necessary for removal purposes, introduction within and at certain locations, or other similar situations that utilize a horizontal operation, such activities have proven valuable for various economic bases.","Typically, such material movement through vertical and/or horizontal pipes and tubes requires a significant amount of energy from vacuum and air conveyance systems due to gravity effects, laminar flow limitations, and conveyance speed requirements, at least.","In terms of vacuum systems, air conveyance can only transport materials a certain distance and at a certain maximum loading speed, dependent on a number of factors, such as material weight, material density, and pipe or tube diameter.","Dynamic pressure through such devices are measurable, at least in terms of fluid dynamics, by the equation: in-line-formulae description=\"In-line Formulae\" end=\"lead\"?","q= ½ p*v 2 in-line-formulae description=\"In-line Formulae\" end=\"tail\"?","wherein q is dynamic pressure measured in Pascals, p is fluid density, and v is velocity through the device.","Such dynamic pressure is equal to the difference between stagnation pressure and static pressure.","There is thus a need to provide an effective change in such dynamic pressure measurements within a vacuum column (or air conveyance system) in order to provide greater efficiencies.","To that end, as is stated in the conservation of energy theorem, energy is constant and neither created nor destroyed, just changed in terms of form.","Thus, for instance, energy from air (or other introduced gas) exhibits a pressure stream that angularly strikes the pipe/tube/cylinder wall and modifies the dynamic pressure of the vacuum column during operation.","Such changes effectively evince reductions in energy to move materials in such devices as a result.","The problem, however, remains that the energy required for such vacuum pressure applications is significant for any such effect.","There thus exists a need to provide improvements in materials transport through such pipe/tube systems, particularly in terms of reducing the energy necessary to undertake such a task without appreciably decreasing materials transport rates (or transversely, increasing such rates with similar energy output measurements).","To date, such has not been effectively provided within the pertinent industries.","For instance, vacuum devices are standard to allow for such transport from a certain desired location.","Although such devices may provide a relatively effective means for conveyance in these situations, the energy required for operation, particularly if the materials are of, again, significant weight and/or density, and if the pipe/tube is of a limited diameter, can be extremely high.","A means to permit more effective movement through the selected tube/pipe in conjunction with a vacuum system would be highly prized, specifically with the reduced need for vacuum strength for the overall desired effect.","Thus, for instance, vacuum systems for the removal of waste from various locations (such as street sweepers, septic tank cleaners, and the like), as well as solid particulate transporters (such as for, for instance, fertilizer, salt, silicon dioxide, and the like, movement devices) for manufacturing or other like operations, and even within mechanical valve-like devices (such as synthetic heart valves, for instance), all suffer from the same associated limitations.","Although some transport to and through such devices may be accomplished to a certain degree, their effectiveness has proven compromised when coupled to the necessary energy generation needed for operation and/or the valves themselves lack the needed effective transport result at the rate and in the same manner as is necessary for proper actions within the selected milieu.","Likewise, in situations where air conveyance (or other type of forwardly forced material movement) is undertaken, the energy levels needed can be excessive for effective results.","Additionally, the forced air operation may face significant difficulties in terms of laminar flow through the selected pipe/tube due to turbulence and density of the materials themselves.","Continued forced air may result, for instance, in uneven packing of solids and inner surface adhesion for liquids (as well as potential turbulence with gases).","This uneven action may also result in uneven blending of materials during transport in certain circumstances that may prove deleterious for the overall operation, as well.","In any event, there exists a great need to provide improved materials transport potential with increased efficiency of vacuum and air conveyance systems in terms of both/either energy levels needed for effective transport and/or faster transport times with lower energy levels required.","Additionally, a device and/or method that allows for more effective blending of transported materials in such a situation would also be desirable in some situations.","To date, however, such a system or systems has yet to be provided the pertinent industries that meet such improved energy output levels, at least."],[" ADVANTAGES AND SUMMARY OF THE INVENTION Thus, one significant advantage of the present invention is the ability to reduce dynamic pressures within a conveyance tube/pipe with energy levels far lower than for typical air or vacuum conveyance applications.","Another advantage is the ability to utilize such a structure within any type of material conveyance application utilization a tube/pipe/cylinder device.","Yet another advantage of the inventive system is the ability to reduce ineffective and deleterious turbulence within the subject pipe/tube/cylinder thereby allowing not only faster materials transport but also more effective blending of introduced materials therein during transport.","Accordingly, the invention encompasses a materials transport device including a cylinder, pipe, and/or tube conveyance component having an external portion and an internal portion, wherein said conveyance component includes at least two (preferably three or more) injectors providing internal introduction of forced fluids angularly within the internal portion of said conveyance component, wherein said injectors are aligned to provide similar angles of fluid introduction within said conveyance component internal portion, and wherein said injectors are housed on the external portion of said conveyance component.","Also encompassed within this invention is the materials transport device as noted above and including fluid source component that is connected separately to each injector, thereby introducing the same pressure and velocity fluid within the conveyance component internal portion during operation.","Further encompassed within this invention is a method of providing materials transport utilizing the transport device as described above.","As well, the transport device provided in the form of a solids transport, a liquid transport, a gas transport, and in the form of a valve-like structure, vacuum-assisted structure, and/or air or liquid conveyance structure, is also encompassed herein.","In essence, the overall inventive transport device is one that allows for more efficient materials transport through the utilization of the plurality of injectors introducing similar and simultaneously introduced fluids within the internal portion of the conveyance component thereof.","In this manner, the term fluids is intended to include, without limitation, a liquid, a gas, or mixtures and/or combinations of multiple liquids, multiple gases, or both gases and liquids.","Such a result is achieved through the introduction of pressurized fluid via a plurality of injectors situated evenly around the circumference of the subject tube, pipe, and/or cylinder, and angled uniformly (at any angle that aims into the internal portion of the conveyance component of the device; a range of from 1 to 75°, with from 5 to 45° more preferred, and from about 10 to 30° potentially most preferred) for an even pressure injection of fluid within the conveyance component thereof.","The injection of such fluids at specified angles and at selected pressures and/or velocities allows for the internal generation of a vortex effect within the conveyance component which, in turn, increases the speed of materials transport, reduces turbulence (and thus dynamic pressures) within the device, and, overall, allows for energy reductions in terms of assisting air or liquid conveyance or vacuum device utilization for such transport purposes through the overall device.","Whether horizontally or vertically aligned, and whether such a line includes both horizontal and vertical configurations to allow transport from one location to another, the inclusion of such a plurality of injectors for such a purpose has proven effective for such improved transport results.","In effect, the inventive materials transport device includes the conveyance component that changes the dynamic pressure of the vacuum column therein through the creation of a vortex effect caused when the introduced pressurized air angularly strikes the tubular cylinder wall.","Such a result effectively modifies the atmospheric pressure inside the tubular cylinder, thus allowing the vortex effect to modify the internal differential pressure.","The versatile nature of such a configuration is shown as typical vacuum systems, fuel injector systems (for automated vehicles, for instance), air conveyance devices, and even synthetic heart valves (that provide a vortex effect that is the normal action of natural heart valve structures; typical mechanical valves do not accord such prized and “natural” effects, thus leading to the inventive valve devices discussed herein according far better results for typical human circulatory/vascular system actions).","Additionally, in terms of, for instance, fuel injector systems, the ability to utilize overflow fuel as the base injected fluid not only improves overall effectiveness and efficiency of the overall device from a energy level standpoint, but also in terms of reduction of “waste” fuel as the potential exists for far more fuel to be actually utilized within the overall activity than for typical, standard fuel injections systems utilized today.","As such, as noted above, this multiple injector vortex production effect thus permits a relatively simple add-on to standard materials transport systems (such as the removal of a tubing component and replacement with one including the multi-injector structure included) to permit production of such an effective energy reduction result.","In other respects, the system may include the addition or inclusion of a blower, vein, or vacuum system attached to a base vacuum accelerator, as well.","Such an overall configuration utilizing the inventive device requires less energy to perform the same amount of work of materials transport as without.","In such situations, then, significant savings can also be realized by utilizing smaller engines and motors to perform standard vacuum activities without losing any effectiveness.","The ability to reduce the overall engine size to this degree may result in the consumption of less fuel and energy since the engine can run at full effectiveness but at fewer revolutions per minute, thereby also saving component life on the systems as well.","Furthermore, the utilization of a vacuum accelerator with the inventive device can allow for the application of a negative pressure vacuum system thereto, permitting multiple reductions in energy since the base vacuum does not require increased energy levels for full capacity in performance.","Additionally, the application of such a vacuum accelerator to a centrifugal or centrifical compressor (or any air conveyance system, for that matter), the vacuum accelerator can function in a similar manner, albeit at a different work ratio.","In such air conveyance systems, in other words, the added vacuum accelerator aids in reducing frictional drag within the transport device and consequently aids to reduce the natural force of gravity on the conveyed material, as well.","This capability then permits an overall reduction in the amount of energy required to move such conveyed materials through any applied transport pipe or cylinder.","In one example, then, a vacuum accelerator may be placed in line with an air conveyance column; the resultant vacuum accelerator helps the air conveyance system move material faster and with less energy than an air conveyance system without a vacuum accelerator, ostensibly modifying the system into an air conveyance accelerator.","Another application of the inventive device may be the utilization of such a vacuum accelerator within industrial plants in order to move liquids and solids in plant lines at reduced energy costs and at higher velocities.","As it applies to horizontal, vertical, or even diagonal transport lines, such a device helps achieve greater efficiencies as noted above.","Furthermore, such a device may be utilized to alter or mix substances for industrial and food service applications.","As above, such is achieved through the introduction of the pressurized fluid via the plurality of injectors situated evenly around the circumference of the subject tube, pipe, and/or cylinder, and angled uniformly for an even pressure injection of fluid within the conveyance component thereof.","Added to such a device, then, is the ability, for instance, to create an effective and thorough mixing result during transport of materials through the generation of such a vortex effect.","Coupled to such a potential operation could be variations in temperatures (external to internal, for instance); if such temperatures are varied in such a respect, the transport device could effective heat or cool the transported materials, permitting not only thorough mixing, but possible modifications in the substances themselves.","Again, this permits not only a reduction in energy for transport purposes, but the potential for reduced energy requirements for mixing as well, thereby increasing the overall effectiveness and efficiency of the entire system.","In one non-limiting example, with ice cream raw materials passed through the inventive device, the mixing and efficiency of moving and condensing the end product consistency could be greatly improved.","With the natural formation of an electro-magnetic field when kinetic energy is transformed into dynamic pressure, there further exists the potential for improved blending of such substances passing through the vortex effect at a molecular level, too.","Such a result could occur at a particle basis after passing through the produced vortex since it could also be (theoretically) super-heated or super cooled through temperature controls.","Such blending benefits could thus also aid in the medical and chemical fields, respectively, particularly to blend substances into compounds.","Another application in the medical field would be in the blending of medicines for the human body, particularly as this device permits such mixing, again, while being transported, rather than prior to or after such a blending step.","One particularly effective application for the inventive device is medically based in terms of synthetic valves for the human heart.","Blood flow into and from the human heart is accomplished through certain valves that are known to create a natural vortex effect that spins off negative charges.","Artificial heart replacement valves do not provide similar effects, thus limiting the effectiveness of such synthetic structures.","For instance, if such an artificial valve could spin off negative charges in the left ventricle, optimal blood transport results could be realized.","Unfortunately, such is not the case, and the standard artificial valves create far reduced levels of blood flow within the patient's body.","The present invention can be properly sized and configured to utilize blood as the injected fluid and could be utilized as a more efficient artificial human heart replacement valve that more closely simulates the actual human circulatory system.","In comparison with standard artificial heart valves, the inventive device could also reduce clotting and other undesirable factors, as well.","In terms of production particulars, as examples, a vacuum accelerator materials transport device of the present invention may be constructed of a variety of materials such as steel, abrasion resistant steel, extend steel, corten steel, polyvinyl chloride, plastic resin, glass, all forms of stainless or precious metals, aluminum, alloys, copper, bronze, and the like (including any combinations thereof).","For production purposes, a manufacturer would typically start with a tube or cylindrical shaped structure and add flanges thereto.","These flanges are normally constructed of the same material as the tube.","Flanges can be either band lock, flat flange, seamless, bolt able, and or weld able or clamp together flanges of any nature.","The flanges allow for attachment to other tubes/pipes/cylinders at either end to permit reliable introduction of the conveyance component of the overall materials transport device.","Once securely in place, the overall device may be utilized with the injectors connected to and introducing a fluid source at the necessary angles within the internal portion of the conveyance component to achieve the desired vortex effect and thus the overall improvements in materials transport efficiencies."],["CROSS-REFERENCE TO RELATED APPLICATIONS This application is a divisional of and claims priority to pending U.S. patent application Ser.","No.","14/283,218, filed on May 21, 2014, which claims the benefit of U.S.","Provisional Patent Application No.","61/855,655, now expired, filed on May 20, 2013.The entirety of both parent and grand-parent applications are herein incorporated by reference.","FIELD OF THE INVENTION A tubular or cylindrical unit that creates a vortex effect with externally supplied pressurized fluid injected angularly within a transport structure is provided.","Such a unit is utilized to either accelerate the vacuum and/or air conveyance of liquids, solid aggregates, and gases, reduce the energy required for such materials transport processes, or both.","Such a result is achieved through the introduction of pressurized fluid via a plurality of injectors situated evenly around the circumference of the subject tube, pipe, and/or cylinder, and angled uniformly for an even pressure injection of fluid within the conveyance component thereof.","In effect, through such injection of pressurized fluid, the overall transport system may be operated at significantly reduced cost while increasing the efficiency of overall vacuum and air conveyance systems simultaneously.","The method of utilization of such a device is also encompassed within this invention.","BACKGROUND OF THE INVENTION Transport of materials, whether liquids, solids, and even gases, has been of enormous importance for a myriad of reasons.","Whether necessary for removal purposes, introduction within and at certain locations, or other similar situations that utilize a horizontal operation, such activities have proven valuable for various economic bases.","Typically, such material movement through vertical and/or horizontal pipes and tubes requires a significant amount of energy from vacuum and air conveyance systems due to gravity effects, laminar flow limitations, and conveyance speed requirements, at least.","In terms of vacuum systems, air conveyance can only transport materials a certain distance and at a certain maximum loading speed, dependent on a number of factors, such as material weight, material density, and pipe or tube diameter.","Dynamic pressure through such devices are measurable, at least in terms of fluid dynamics, by the equation: q=½p*v2 wherein q is dynamic pressure measured in Pascals, p is fluid density, and v is velocity through the device.","Such dynamic pressure is equal to the difference between stagnation pressure and static pressure.","There is thus a need to provide an effective change in such dynamic pressure measurements within a vacuum column (or air conveyance system) in order to provide greater efficiencies.","To that end, as is stated in the conservation of energy theorem, energy is constant and neither created nor destroyed, just changed in terms of form.","Thus, for instance, energy from air (or other introduced gas) exhibits a pressure stream that angularly strikes the pipe/tube/cylinder wall and modifies the dynamic pressure of the vacuum column during operation.","Such changes effectively evince reductions in energy to move materials in such devices as a result.","The problem, however, remains that the energy required for such vacuum pressure applications is significant for any such effect.","There thus exists a need to provide improvements in materials transport through such pipe/tube systems, particularly in terms of reducing the energy necessary to undertake such a task without appreciably decreasing materials transport rates (or transversely, increasing such rates with similar energy output measurements).","To date, such has not been effectively provided within the pertinent industries.","For instance, vacuum devices are standard to allow for such transport from a certain desired location.","Although such devices may provide a relatively effective means for conveyance in these situations, the energy required for operation, particularly if the materials are of, again, significant weight and/or density, and if the pipe/tube is of a limited diameter, can be extremely high.","A means to permit more effective movement through the selected tube/pipe in conjunction with a vacuum system would be highly prized, specifically with the reduced need for vacuum strength for the overall desired effect.","Thus, for instance, vacuum systems for the removal of waste from various locations (such as street sweepers, septic tank cleaners, and the like), as well as solid particulate transporters (such as for, for instance, fertilizer, salt, silicon dioxide, and the like, movement devices) for manufacturing or other like operations, and even within mechanical valve-like devices (such as synthetic heart valves, for instance), all suffer from the same associated limitations.","Although some transport to and through such devices may be accomplished to a certain degree, their effectiveness has proven compromised when coupled to the necessary energy generation needed for operation and/or the valves themselves lack the needed effective transport result at the rate and in the same manner as is necessary for proper actions within the selected milieu.","Likewise, in situations where air conveyance (or other type of forwardly forced material movement) is undertaken, the energy levels needed can be excessive for effective results.","Additionally, the forced air operation may face significant difficulties in terms of laminar flow through the selected pipe/tube due to turbulence and density of the materials themselves.","Continued forced air may result, for instance, in uneven packing of solids and inner surface adhesion for liquids (as well as potential turbulence with gases).","This uneven action may also result in uneven blending of materials during transport in certain circumstances that may prove deleterious for the overall operation, as well.","In any event, there exists a great need to provide improved materials transport potential with increased efficiency of vacuum and air conveyance systems in terms of both/either energy levels needed for effective transport and/or faster transport times with lower energy levels required.","Additionally, a device and/or method that allows for more effective blending of transported materials in such a situation would also be desirable in some situations.","To date, however, such a system or systems has yet to be provided the pertinent industries that meet such improved energy output levels, at least.","ADVANTAGES AND SUMMARY OF THE INVENTION Thus, one significant advantage of the present invention is the ability to reduce dynamic pressures within a conveyance tube/pipe with energy levels far lower than for typical air or vacuum conveyance applications.","Another advantage is the ability to utilize such a structure within any type of material conveyance application utilization a tube/pipe/cylinder device.","Yet another advantage of the inventive system is the ability to reduce ineffective and deleterious turbulence within the subject pipe/tube/cylinder thereby allowing not only faster materials transport but also more effective blending of introduced materials therein during transport.","Accordingly, the invention encompasses a materials transport device including a cylinder, pipe, and/or tube conveyance component having an external portion and an internal portion, wherein said conveyance component includes at least two (preferably three or more) injectors providing internal introduction of forced fluids angularly within the internal portion of said conveyance component, wherein said injectors are aligned to provide similar angles of fluid introduction within said conveyance component internal portion, and wherein said injectors are housed on the external portion of said conveyance component.","Also encompassed within this invention is the materials transport device as noted above and including fluid source component that is connected separately to each injector, thereby introducing the same pressure and velocity fluid within the conveyance component internal portion during operation.","Further encompassed within this invention is a method of providing materials transport utilizing the transport device as described above.","As well, the transport device provided in the form of a solids transport, a liquid transport, a gas transport, and in the form of a valve-like structure, vacuum-assisted structure, and/or air or liquid conveyance structure, is also encompassed herein.","In essence, the overall inventive transport device is one that allows for more efficient materials transport through the utilization of the plurality of injectors introducing similar and simultaneously introduced fluids within the internal portion of the conveyance component thereof.","In this manner, the term fluids is intended to include, without limitation, a liquid, a gas, or mixtures and/or combinations of multiple liquids, multiple gases, or both gases and liquids.","Such a result is achieved through the introduction of pressurized fluid via a plurality of injectors situated evenly around the circumference of the subject tube, pipe, and/or cylinder, and angled uniformly (at any angle that aims into the internal portion of the conveyance component of the device; a range of from 1 to 75°, with from 5 to 45° more preferred, and from about 10 to 30° potentially most preferred) for an even pressure injection of fluid within the conveyance component thereof.","The injection of such fluids at specified angles and at selected pressures and/or velocities allows for the internal generation of a vortex effect within the conveyance component which, in turn, increases the speed of materials transport, reduces turbulence (and thus dynamic pressures) within the device, and, overall, allows for energy reductions in terms of assisting air or liquid conveyance or vacuum device utilization for such transport purposes through the overall device.","Whether horizontally or vertically aligned, and whether such a line includes both horizontal and vertical configurations to allow transport from one location to another, the inclusion of such a plurality of injectors for such a purpose has proven effective for such improved transport results.","In effect, the inventive materials transport device includes the conveyance component that changes the dynamic pressure of the vacuum column therein through the creation of a vortex effect caused when the introduced pressurized air angularly strikes the tubular cylinder wall.","Such a result effectively modifies the atmospheric pressure inside the tubular cylinder, thus allowing the vortex effect to modify the internal differential pressure.","The versatile nature of such a configuration is shown as typical vacuum systems, fuel injector systems (for automated vehicles, for instance), air conveyance devices, and even synthetic heart valves (that provide a vortex effect that is the normal action of natural heart valve structures; typical mechanical valves do not accord such prized and “natural” effects, thus leading to the inventive valve devices discussed herein according far better results for typical human circulatory/vascular system actions).","Additionally, in terms of, for instance, fuel injector systems, the ability to utilize overflow fuel as the base injected fluid not only improves overall effectiveness and efficiency of the overall device from a energy level standpoint, but also in terms of reduction of “waste” fuel as the potential exists for far more fuel to be actually utilized within the overall activity than for typical, standard fuel injections systems utilized today.","As such, as noted above, this multiple injector vortex production effect thus permits a relatively simple add-on to standard materials transport systems (such as the removal of a tubing component and replacement with one including the multi-injector structure included) to permit production of such an effective energy reduction result.","In other respects, the system may include the addition or inclusion of a blower, vein, or vacuum system attached to a base vacuum accelerator, as well.","Such an overall configuration utilizing the inventive device requires less energy to perform the same amount of work of materials transport as without.","In such situations, then, significant savings can also be realized by utilizing smaller engines and motors to perform standard vacuum activities without losing any effectiveness.","The ability to reduce the overall engine size to this degree may result in the consumption of less fuel and energy since the engine can run at full effectiveness but at fewer revolutions per minute, thereby also saving component life on the systems as well.","Furthermore, the utilization of a vacuum accelerator with the inventive device can allow for the application of a negative pressure vacuum system thereto, permitting multiple reductions in energy since the base vacuum does not require increased energy levels for full capacity in performance.","Additionally, the application of such a vacuum accelerator to a centrifugal or centrifical compressor (or any air conveyance system, for that matter), the vacuum accelerator can function in a similar manner, albeit at a different work ratio.","In such air conveyance systems, in other words, the added vacuum accelerator aids in reducing frictional drag within the transport device and consequently aids to reduce the natural force of gravity on the conveyed material, as well.","This capability then permits an overall reduction in the amount of energy required to move such conveyed materials through any applied transport pipe or cylinder.","In one example, then, a vacuum accelerator may be placed in line with an air conveyance column; the resultant vacuum accelerator helps the air conveyance system move material faster and with less energy than an air conveyance system without a vacuum accelerator, ostensibly modifying the system into an air conveyance accelerator.","Another application of the inventive device may be the utilization of such a vacuum accelerator within industrial plants in order to move liquids and solids in plant lines at reduced energy costs and at higher velocities.","As it applies to horizontal, vertical, or even diagonal transport lines, such a device helps achieve greater efficiencies as noted above.","Furthermore, such a device may be utilized to alter or mix substances for industrial and food service applications.","As above, such is achieved through the introduction of the pressurized fluid via the plurality of injectors situated evenly around the circumference of the subject tube, pipe, and/or cylinder, and angled uniformly for an even pressure injection of fluid within the conveyance component thereof.","Added to such a device, then, is the ability, for instance, to create an effective and thorough mixing result during transport of materials through the generation of such a vortex effect.","Coupled to such a potential operation could be variations in temperatures (external to internal, for instance); if such temperatures are varied in such a respect, the transport device could effective heat or cool the transported materials, permitting not only thorough mixing, but possible modifications in the substances themselves.","Again, this permits not only a reduction in energy for transport purposes, but the potential for reduced energy requirements for mixing as well, thereby increasing the overall effectiveness and efficiency of the entire system.","In one non-limiting example, with ice cream raw materials passed through the inventive device, the mixing and efficiency of moving and condensing the end product consistency could be greatly improved.","With the natural formation of an electro-magnetic field when kinetic energy is transformed into dynamic pressure, there further exists the potential for improved blending of such substances passing through the vortex effect at a molecular level, too.","Such a result could occur at a particle basis after passing through the produced vortex since it could also be (theoretically) super-heated or super cooled through temperature controls.","Such blending benefits could thus also aid in the medical and chemical fields, respectively, particularly to blend substances into compounds.","Another application in the medical field would be in the blending of medicines for the human body, particularly as this device permits such mixing, again, while being transported, rather than prior to or after such a blending step.","One particularly effective application for the inventive device is medically based in terms of synthetic valves for the human heart.","Blood flow into and from the human heart is accomplished through certain valves that are known to create a natural vortex effect that spins off negative charges.","Artificial heart replacement valves do not provide similar effects, thus limiting the effectiveness of such synthetic structures.","For instance, if such an artificial valve could spin off negative charges in the left ventricle, optimal blood transport results could be realized.","Unfortunately, such is not the case, and the standard artificial valves create far reduced levels of blood flow within the patient's body.","The present invention can be properly sized and configured to utilize blood as the injected fluid and could be utilized as a more efficient artificial human heart replacement valve that more closely simulates the actual human circulatory system.","In comparison with standard artificial heart valves, the inventive device could also reduce clotting and other undesirable factors, as well.","In terms of production particulars, as examples, a vacuum accelerator materials transport device of the present invention may be constructed of a variety of materials such as steel, abrasion resistant steel, extend steel, corten steel, polyvinyl chloride, plastic resin, glass, all forms of stainless or precious metals, aluminum, alloys, copper, bronze, and the like (including any combinations thereof).","For production purposes, a manufacturer would typically start with a tube or cylindrical shaped structure and add flanges thereto.","These flanges are normally constructed of the same material as the tube.","Flanges can be either band lock, flat flange, seamless, bolt able, and or weld able or clamp together flanges of any nature.","The flanges allow for attachment to other tubes/pipes/cylinders at either end to permit reliable introduction of the conveyance component of the overall materials transport device.","Once securely in place, the overall device may be utilized with the injectors connected to and introducing a fluid source at the necessary angles within the internal portion of the conveyance component to achieve the desired vortex effect and thus the overall improvements in materials transport efficiencies.","BRIEF DESCRIPTION OF THE DRAWINGS FIG.","1 provides a top view of a large diameter (60″) pipe conveyance component of the present invention.","FIG.","2 shows a front view of the same pipe of FIG.","1.FIG.","3 shows a top perspective view of the same pipe of FIG.","1.FIG.","4 shows a front cross-sectional view of the conveyance component pipe of FIG.","1.FIG.","5 provides a top view of a small diameter (18″) pipe conveyance component of the present invention.","FIG.","6 shows a front view of the same pipe of FIG.","5.FIG.","7 shows a top perspective view of the same pipe of FIG.","5.FIG.","8 shows a front cross-sectional view of the conveyance component pipe of FIG.","5.FIG.","9 provides a top view of a band-lock pipe conveyance component of the present invention.","FIG.","10 shows a front view of the same pipe of FIG.","9.FIG.","11 shows a top perspective view of the same pipe of FIG.","9.FIG.","12 shows a front cross-sectional view of the conveyance component pipe of FIG.","9.FIG.","13 provides a top view of a vacuum/air decelerator pipe conveyance component of the present invention.","FIG.","14 shows a front view of the same pipe of FIG.","13.FIG.","15 shows a top perspective view of the same pipe of FIG.","13.FIG.","16 shows a front cross-sectional view of the conveyance component pipe of FIG.","13.FIG.","17 provides a top view of a PVC pipe conveyance component of the present invention.","FIG.","18 shows a top perspective view of the same pipe of FIG.","7.FIG.","19 shows a front cross-sectional view of the conveyance component pipe of FIG.","17.FIG.","20 provides a top view of an industrial air accelerator-type conveyance component of the present invention.","FIG.","21 shows a front view of the same pipe of FIG.","20.FIG.","22 shows a top perspective view of the same pipe of FIG.","20.FIG.","23 shows a front cross-sectional view of the conveyance component pipe of FIG.","20.FIG.","24 provides a top view of a high-pressure water system vacuum accelerator-type pipe conveyance component of the present invention.","FIG.","25 shows a front view of the same pipe of FIG.","24.FIG.","26 shows a top perspective view of the same pipe of FIG.","24.FIG.","27 shows a front cross-sectional view of the conveyance component pipe of FIG.","24.FIG.","28 provides a top view of a positive displacement industrial vacuum loader pipe conveyance component of the present invention.","FIG.","29 shows a front view of the same pipe of FIG.","28.FIG.","30 shows a top perspective view of the same pipe of FIG.","28.FIG.","31 shows a front cross-sectional view of the conveyance component pipe of FIG.","28.FIG.","32 provides a top view of an air-style industrial vacuum accelerator pipe conveyance component of the present invention.","FIG.","33 shows a front view of the same pipe of FIG.","32.FIG.","34 shows a top perspective view of the same pipe of FIG.","32.FIG.","35 shows a front cross-sectional view of the conveyance component pipe of FIG.","32.FIG.","36 provides a top view of a water transmission vacuum accelerator long distance transport pipe conveyance component of the present invention.","FIG.","37 shows a front view of the same pipe of FIG.","36.FIG.","38 shows a top perspective view of the same pipe of FIG.","36.FIG.","39 shows a front cross-sectional view of the conveyance component pipe of FIG.","36.FIG.","40 provides a top view of a vacuum particle accelerator/collider pipe conveyance component of the present invention.","FIG.","41 shows a front view of the same pipe of FIG.","40.FIG.","42 shows a top perspective view of the same pipe of FIG.","40.FIG.","43 shows a front cross-sectional view of the conveyance component pipe of FIG.","40.FIG.","44 provides a top view of a vacuum accelerator prosthetic heart valve pipe conveyance component of the present invention.","FIG.","45 shows a front view of the same pipe of FIG.","44.FIG.","46 shows a top perspective view of the same pipe of FIG.","44.FIG.","47 shows a front cross-sectional view of the conveyance component pipe of FIG.","44.FIG.","48 provides a top view of a fuel injector add-on pipe conveyance component of the present invention.","FIG.","49 shows a front view of the same pipe of FIG.","48.FIG.","50 shows a partial cut-away front perspective view of a fuel injector to which the inventive conveyance component of FIG.","48 is added.","FIG.","51 shows a front cross-sectional view of the conveyance component pipe of FIG.","48.FIG.","52 is a top perspective view of the same pipe of FIG.","48.DETAILED DESCRIPTION OF THE DRAWINGS AND PREFERRED EMBODIMENTS OF THE INVENTION Without any intention of limiting the breadth and scope of the overall inventive method, the following descriptions of the accompanying drawings provide a number of potentially preferred embodiments of the inventive overall transport improvement device.","The accompanying FIGS.","1-52) provided herein all pertain to different versions of conveyance components that may be utilized in conjunction with the broadly defined inventive materials transport device.","As noted above and herein, the basic structure is a pipe, tube, or cylinder to which a plurality of injectors has been incorporated within the conveyance component from an external source and introduced for injection within the internal portion at uniform angles and evenly spaced around the circumference of the base tube, pipe, and/or cylinder.","As well, the injectors are preferably connected simultaneously to the same fluid source in order to introduce the same fluid at the same pressure in order to generate the desired vortex effect within the conveyance component of the materials transport device.","In order to achieve such results, the structures may be produced in the following manner, dependent, certainly, upon specific sizes of base structures as it concerns the end-use desired.","Thus, for manufacturing purposes, one manner of achieving such conveyance components of the present invention would be within the following steps: 1.A cylindrical tube is provided made of metal or alloy made of sufficient diameter to connect to existing vacuum column with ports drilled in tube.","2.Weld a coupling to tube.","3.Calibrate and attach air couplings to the cylindrical tube.","4.Attach any necessary flanges to the cylindrical tube.","5.Attach air lines to fittings.","6.Install an air manifold.","7.Install a variable air valve (whether mechanical, pneumatic, electrical, electronic or hydraulically actuated, depending on the application).","8.Connect an air supply to the manifold unit.","9.Connect a pressure gauge to the air supply.","10.Insert nozzles into the couplers.","Taking these base steps in conjunction with FIGS.","1-4, for instance, provided is a 60 inch diameter tubular cylinder 1 that is drilled for ports couplings 2 and are welded strategically to the outside cylinder wall.","The orifice size of the port with or without nozzles can be varied as well as the angle of the port to increase or decrease the speed and efficiency of the vacuum accelerator 3.The air couplings are attached to the ports on the tubular cylinder 2.Flanges 4 are attached to the end of the tube 1 in various configurations, so that the vacuum accelerator can be attached to the vacuum or air conveyance columns.","Air lines 5 are then attached to fittings, the air manifold 6 (4-way valve) to distribute air where needed and a separate airline for air inlet.","The variable air valve 7 is then in place to control flow and pressure and is connected to the air supply 8.The pressure gauge 9 is then attached to monitor the overall unit.","The nozzles 10 are then inserted within the couplers 2 to permit the injection of the gas (fluid) within the internal portion of the conveyance component of the unit.","Viewing, then FIGS.","5-8, the same basic structure is accorded but with a smaller (18 inch) diameter tubular cylinder 11.Such a cylinder 11 is, as above, drilled for ports couplings 12 and are welded strategically to the outside cylinder wall.","The orifice size of the port with or without nozzles can be varied as well as the angle of the port to increase or decrease the speed and efficiency of the vacuum accelerator 13.The air couplings are attached to the ports on the tubular cylinder 12.Flanges 14 are attached to the end of the tube 11 in various configurations, so that the vacuum accelerator can be attached to the vacuum or air conveyance columns.","Air lines 15 are then attached to fittings, the air manifold 16 (4-way valve) to distribute air where needed and a separate airline for air inlet.","The variable air valve 17 is then in place to control flow and pressure and is connected to the air supply 18.The pressure gauge 19 is then attached to monitor the overall unit.","The nozzles 20 are then inserted within the couplers 12 to permit the injection of the gas (fluid) within the internal portion of the conveyance component of the unit.","FIGS.","9-12 pertain to an even smaller (8 inch) diameter tubular cylinder 21 with a band lock flange 24.Such a cylinder 21 is, as above, drilled for ports couplings 22 and are welded strategically to the outside cylinder wall.","The orifice size of the port with or without nozzles can be varied as well as the angle of the port to increase or decrease the speed and efficiency of the vacuum accelerator 23.The air couplings are attached to the ports on the tubular cylinder 21.The band lock flanges 24 are attached to the end of the tube 21 in various configurations, so that the vacuum accelerator can be attached to the vacuum or air conveyance columns.","Air lines 25 are then attached to fittings, the air manifold 26 (4-way valve) to distribute air where needed and a separate airline for air inlet.","The variable air valve 27 is then in place to control flow and pressure and is connected to the air supply 28.The pressure gauge 29 is then attached to monitor the overall unit.","The nozzles 30 are then inserted within the couplers 22 to permit the injection of the gas (fluid) within the internal portion of the conveyance component of the unit.","An inventive vacuum/air decelerator configuration is shown in FIGS.","13-16 with a tubular cylinder 31.Such a cylinder 31 is, as above, drilled for ports couplings 32 and are welded strategically to the outside cylinder wall.","The orifice size of the port with or without nozzles can be varied as well as the angle of the port to increase or decrease the speed and efficiency of the vacuum accelerator 33.The air couplings are attached to the ports on the tubular cylinder 32.Flanges 34 are attached to the end of the tube 31 in various configurations, so that the vacuum accelerator can be attached to the vacuum or air conveyance columns.","Air lines 35 are then attached to fittings, the air manifold 36 (4-way valve) to distribute air where needed and a separate airline for air inlet.","The variable air valve 37 is then in place to control flow and pressure and is connected to the air supply 38.The pressure gauge 39 is then attached to monitor the overall unit.","The nozzles 40 are then inserted within the couplers 32 to permit the injection of the gas (fluid) within the internal portion of the conveyance component of the unit.","A polyvinyl chloride application is shown in FIGS.","17-19 with a tubular PVC cylinder 41.Such a cylinder 41 is, as above, drilled for ports couplings 42 and are welded strategically to the outside cylinder wall.","The orifice size of the port with or without nozzles can be varied as well as the angle of the port to increase or decrease the speed and efficiency of the vacuum accelerator 43.The air couplings are attached to the ports on the tubular cylinder 42.PVC flanges 44 are attached to the end of the tube 41 in various configurations, so that the vacuum accelerator can be attached to the vacuum or air conveyance columns.","Air lines 45 are then attached to fittings, the air manifold 46 (4-way valve) to distribute air where needed and a separate airline for air inlet.","The variable air valve 47 is then in place to control flow and pressure and is connected to the air supply 48.The pressure gauge 49 is then attached to monitor the overall unit.","The nozzles 50 are then inserted within the couplers 42 to permit the injection of the gas (fluid) within the internal portion of the conveyance component of the unit.","An inventive industrial street sweeper-type regenerative air style machine air accelerator conveyance component is shown in FIGS.","20-23 with a tubular cylinder 51.Such a cylinder 51 is, as above, drilled for ports couplings 52 and are welded strategically to the outside cylinder wall.","The orifice size of the port with or without nozzles can be varied as well as the angle of the port to increase or decrease the speed and efficiency of the vacuum accelerator 53.The air couplings are attached to the ports on the tubular cylinder 52.Flanges 54 are attached to the end of the tube 51 in various configurations, so that the vacuum accelerator can be attached to the vacuum or air conveyance columns.","Air lines 55 are then attached to fittings, the air manifold 56 (4-way valve) to distribute air where needed and a separate airline for air inlet.","The variable air valve 57 is then in place to control flow and pressure and is connected to the air supply 58.The pressure gauge 59 is then attached to monitor the overall unit.","The nozzles 60 are then inserted within the couplers 52 to permit the injection of the gas (fluid) within the internal portion of the conveyance component of the unit.","An inventive high-pressure vacuum accelerator for, for example, water transport, is shown in FIGS.","24-27 with a tubular cylinder 61.Such a cylinder 61 is, as above, drilled for ports couplings 62 and are welded strategically to the outside cylinder wall.","The orifice size of the port with or without nozzles can be varied as well as the angle of the port to increase or decrease the speed and efficiency of the vacuum accelerator 63.The air couplings are attached to the ports on the tubular cylinder 62.Flanges 64 are attached to the end of the tube 61 in various configurations, so that the vacuum accelerator can be attached to the vacuum or air conveyance columns.","Air lines 65 are then attached to fittings, the air manifold 66 (4-way valve) to distribute air where needed and a separate airline for air inlet.","The variable air valve 67 is then in place to control flow and pressure and is connected to the air supply 68.The pressure gauge 69 is then attached to monitor the overall unit.","The nozzles 70 are then inserted within the couplers 62 to permit the injection of the water (fluid) within the internal portion of the conveyance component of the unit.","An inventive industrial vacuum loader for positive displacement is shown in FIGS.","28-31 with a tubular cylinder 71.Such a cylinder 71 is, as above, drilled for ports couplings 72 and are welded strategically to the outside cylinder wall.","The orifice size of the port with or without nozzles can be varied as well as the angle of the port to increase or decrease the speed and efficiency of the vacuum accelerator 73.The air couplings are attached to the ports on the tubular cylinder 72.Flanges 74 are attached to the end of the tube 71 in various configurations, so that the vacuum accelerator can be attached to the vacuum or air conveyance columns.","Air lines 75 are then attached to fittings, the air manifold 76 (4-way valve) to distribute air where needed and a separate airline for air inlet.","The variable air valve 77 is then in place to control flow and pressure and is connected to the air supply 78.The pressure gauge 79 is then attached to monitor the overall unit.","The nozzles 80 are then inserted within the couplers 72 to permit the injection of the gas (fluid) within the internal portion of the conveyance component of the unit.","An inventive industrial street sweeper-type regenerative air style machine vacuum accelerator conveyance component is shown in FIGS.","32-35 with a tubular cylinder 81.Such a cylinder 81 is, as above, drilled for ports couplings 82 and are welded strategically to the outside cylinder wall.","The orifice size of the port with or without nozzles can be varied as well as the angle of the port to increase or decrease the speed and efficiency of the vacuum accelerator 83.The air couplings are attached to the ports on the tubular cylinder 82.Flanges 84 are attached to the end of the tube 81 in various configurations, so that the vacuum accelerator can be attached to the vacuum or air conveyance columns.","Air lines 85 are then attached to fittings, the air manifold 86 (4-way valve) to distribute air where needed and a separate airline for air inlet.","The variable air valve 87 is then in place to control flow and pressure and is connected to the air supply 88.The pressure gauge 89 is then attached to monitor the overall unit.","The nozzles 90 are then inserted within the couplers 82 to permit the injection of the gas (fluid) within the internal portion of the conveyance component of the unit.","An inventive long-distance water transport conveyance component having a 72 inch diameter tubular cylinder 91 is shown in FIGS.","36-39.Such a cylinder 91 is, as above, drilled for ports couplings 92 and are welded strategically to the outside cylinder wall.","The orifice size of the port with or without nozzles can be varied as well as the angle of the port to increase or decrease the speed and efficiency of the vacuum accelerator 93.The air couplings are attached to the ports on the tubular cylinder 92.Screw-type couplers (MPTH) 94 are attached to the end of the tube 91 in various configurations, so that the vacuum accelerator can be attached to the vacuum or air conveyance columns.","Air lines 95 are then attached to fittings, the air manifold 96 (4-way valve) to distribute air where needed and a separate airline for air inlet.","The variable air valve 97 is then in place to control flow and pressure and is connected to the air supply 98.The pressure gauge 99 is then attached to monitor the overall unit.","The nozzles 100 are then inserted within the couplers 92 to permit the injection of the gas (fluid) within the internal portion of the conveyance component of the unit.","An inventive particle accelerator (for a particle collider, for example) is shown in FIGS.","40-43 with a miniature tubular cylinder 101 and a pulse electro-magnet 101A.","Such a cylinder 101 is, as above, drilled for ports couplings 102 and are welded strategically to the outside cylinder wall.","The orifice size of the port with or without nozzles can be varied as well as the angle of the port to increase or decrease the speed and efficiency of the vacuum accelerator 103.The air couplings are attached to the ports on the tubular cylinder 102.Flanges 104 are attached to the end of the tube 101 in various configurations, so that the vacuum accelerator can be attached to the vacuum or air conveyance columns.","Air lines 105 are then attached to fittings, the air manifold 106 (4-way valve) to distribute air where needed and a separate airline for air inlet.","The variable air valve 107 is then in place to control flow and pressure and is connected to the air supply 108.The pressure gauge 109 is then attached to monitor the overall unit.","The nozzles 120 are then inserted within the couplers 102 to permit the injection of the gas (fluid) within the internal portion of the conveyance component of the unit.","An inventive prosthetic heart valve (asymmetrical or symmetrical) vacuum accelerator conveyance component is shown in FIGS.","44-47 with a very small tubular cylinder 111.Such a cylinder 111 is, as above, drilled for ports couplings 112 and are welded strategically to the outside cylinder wall.","The orifice size of the port be varied as well as the angle of the port to increase or decrease the speed and efficiency of the vacuum accelerator 113.Blood is forced through the couplings 113 and nozzles 112 to effectuate the vortex effect within the tube 111.The air couplings 113 are attached to the ports 112 on the tubular cylinder 111.Suture ring flanges 114 are attached to the end of the tube 111 in various configurations, so that the vacuum accelerator can be attached to the vacuum or air conveyance columns in order to act in combination with a valve structure as needed.","An inventive fuel injector with an added conveyance component is shown in FIGS.","48-52 with a tubular cylinder 131.Such a cylinder 131 is, as above, drilled for ports couplings 132 and are welded strategically to the outside cylinder wall.","The orifice size of the port with or without nozzles can be varied as well as the angle of the port to increase or decrease the speed and efficiency of the vacuum accelerator 133.The air couplings are attached to the ports on the tubular cylinder 131.Flanges 134 are attached to the end of the tube 131 in various configurations, so that the vacuum accelerator can be attached to the vacuum or air conveyance columns.","Air lines 135 are then attached to fittings, the air manifold 136 (4-way valve) to distribute air where needed and a separate airline for air inlet.","The variable air valve 137 is then in place to control flow and pressure and is connected to the air supply 138.The pressure gauge 139 is then attached to monitor the overall unit.","The nozzles 140 are then inserted within the couplers 52 to permit the injection of the gas (fluid) within the internal portion of the conveyance component of the unit.","The unit is introduced within a fuel injector 145, including a pressurized fuel line 154, fuel filter 155, an electrical boost attachment 153, a solenoid 152, a plunger 157, a valve spring 151, and a spray tip 150, all housed within a casing 156.When the fuel injector 145 is operated, the fuel pressure can be increased by the conveyance component as described above.","Additionally, the source of the injector supply may be excess fuel that allows for recoupment and less waste thereof for extra economic benefits and efficiencies.","In terms, then, of the actual operation of the invention, for all structures, basically, with a few notable exceptions, the tubular cylinder is to contain the material being conveyed or vacuumed.","The ports with or without orifices are to convey air angularly against the inside sidewall of the cylinder to create negative pressure that creates a vortex effect inside the cylinder.","Calibrate and attach air coupling to cylinder.","The size, angle, and number of couplings depend on the vacuum acceleration required for the application.","For example, a three-inch diameter tube vacuum accelerator might require fewer ports than a four-foot diameter vacuum accelerator.","The angle of the port to the cylinder wall will affect the speed and negative pressure desired for the application.","The flanges are installed to the tube so that it can attach to various vacuum columns inline.","Air lines are attached to the fittings and run to air manifolds for air distribution where needed.","A variable air valve is installed to regulate air flow and pressure and gauge is installed to regulate pressure.","The unit will convey liquids and material even when not attached to vacuum column.","The pressure gauge monitors the unit.","The nozzles inserted into the couplers create directional pressure which increases velocity on the cylinder wall.","The unit is also directional and configured to create vacuum acceleration when installed in the conveyance direction to direct material towards the vacuum in order to create negative pressure, and to create vacuum deceleration when installed in reverse.","The overall components of the device may be of different materials themselves.","In terms of, for instance, the tubular cylinder, such may be varied in size from just a few millimeters to 8-foot in diameter.","As well, then, the tube may be constructed of a variety of materials such as; steel, abrasion-resistant steel, exten steel, corten steel, polyvinyl chloride, plastic resin, urethane, all forms of stainless steel, all forms of precious metals, copper, bronze, or even glass.","The material chosen for the tube depends on the type of material one wants to convey.","Flanges are next added to the cylinder-shaped tube.","These flanges are normally constructed of the same material as the tube.","Flanges can be band lock, flat flange, seamless, weld-able, or clamp together flanges of any nature.","Basically, flange selection depends on the vacuum column to attachment is to be made.","If the vacuum column uses flat flanges, then such should be utilized as well in conjunction with the cylinder.","If the tube is made of metal, flanges may also be welded to the tubular cylinder.","The flanges just serve the purpose of attaching the unit in-line to the vacuum column and or air conveyance column.","Drilling, plasma cutting, torch utilization, etc., may be undertaken, as examples, to make appropriate holes in the tubular cylinder.","The diameter of the holes, the size of the holes, and the number of holes depends on the speed of vacuum accelerator one desires.","Couplings are then attached over the holes drilled in the tube.","It is easier to attach the pressure nozzles into one end of the coupling and then attach the couplings to the tubular cylinder, generally, though not necessarily.","If, for example, the tubular cylinder is metal, then the couplings can be welded, for example, at the correct angle with the nozzle facing the inside wall of the cylinder.","If the tubular cylinder is PVC material, the same process may be followed, but the couplings are preferably cemented, for example, to the cylinder.","The air couplings are then attached to the other end of the couplings that are welded to the tubular cylinder.","The airlines are then attached to the air couplings and then to the air manifold.","The variable air valve is attached to the manifold and a pressure gauge can then be added to monitor unit.","The air supply is connected to the manifold inlet and all is ready to be utilized with the airlines intact within the nozzles.","The size and type of material for the pressure nozzles can be varied to change the acceleration ratios.","Some examples are ceramic nozzles versus carbide nozzles, or abrasion resistant steel nozzles depending on the material to be conveyed.","The diameter and shape of the nozzle orifices can be altered to change the performance.","The orifice size could be a couple of millimeters or less or several feet in diameter, depending on the size of vacuum accelerator needed.","Nozzles may be made from a variety of materials and may be constructed from materials such as straight drilled pipe to very sophisticated tips with elongated holes, broad examples.","The amount of air supplied to the unit can be varied from 1 cfm to hundreds of thousands of cfm.","The size of the vacuum accelerator will depend on what vacuum or air conveyance column or structure one wants to attach the unit to.","The type of air manifold can be varied depending on the application.","Even the size, angle, material of ports can vary.","To use this invention, one would attach the unit to the vacuum or air conveyance column, the liquid supply, or a blood supply, as needed; the supply is initiated and effectively begins the generation of the desired vortex effect, whether in terms of vacuum or air conveyance, whether positive or negative pressures (dependent on the direction of accelerator or decelerator in place).","This invention could be used on street sweepers, environmental and industrial vacuum loaders, septic vacuum trucks and any vacuum or air conveyance system.","This invention would increase productivity of these units at a lower cost.","There are many industrial plant applications that need to convey material more efficiently at reduced costs.","Industrial plants have miles of pipe that they utilize to move materials around their plants.","Many of these plants use positive displacement blowers and or large air conveyance systems.","The inventive vacuum accelerator can be attached to the pipe lines to reduce the frictional drag of the columns and to speed the conveyance of materials throughout the plant.","This inventive device could also be utilized gas and oil pipelines to more efficiently convey materials longer distances at greater speed.","Other variables that would help change dynamic pressure of the vacuum column are as follows: 1.The number of orifices and the location they are placed on a vacuum column.","2.The size, shape and material the port orifices are made out of.","3.If one were to add any type of lubricator to the system to reduce the frictional force.","4.The diameter of the airlines, and the type of material they are made out of.","Some examples are copper, steel, nylon, plastic and alloys.","Thermo plastics and many heat resistant materials as well.","5.The amount of air pressure supplied to the system.","This is usually expressed in cfms.","6.The actual air routing to the air supply, the manifold, and the size and type of manifold can all effect the change in dynamic pressure.","7.Another variable that can be added to my invention to further increase the power of my vortex effect is the addition of a small electro-magnetic field to intensify the vortex effect.","8.The shape of the tubular cylinder can be altered to effect dynamic pressure.","For example, the shape of the tubular cylinder can be hexagonal rather than cylindrical or any irregular shape to affect the energy level from the vortex effect; this will in turn change the dynamic pressure of the vacuum column, and/or the air conveyance column velocity in turn.","9.Another important note is that the vortex effect does not have to be perfectly symmetric to work.","10.The invention device changes the densities and viscosity of substances in the vacuum column and/or air conveyance column.","The energy created by the vortex will aid in the mixing of compounds being introduced to the human body.","It will aid in the dynamic pressure and or air velocity necessary to create the appropriate mixture of compounds, liquids and or gases to achieve the desired result.","Furthermore, in the bonding of substances on a molecular level, and or on an electron, proton and neutron basis, that energy, magnetism and pressure all affect the bonding of elements into compound substances.","Thereby, the tremendous energy naturally found in a vortex, induced on to substances passed through my invention will aid medical science in the more efficient bonding and blending of substances and possibly the creation of new substances.","As the vortex effect creates its own electro-magnetic field.","This device can also change the temperature, thereby altering the characteristics and consistency of substances that passes through my invention.","In other words, it will change the form of the matter that passes through the vortex effect.","Depending on the direction the initial substance is passed through my invention, some substances will change molecularly due to the effects of magnetism on an elemental level.","Substances will end up more negatively or positively charged even on a P orbital basis.","In a science application, this device could also be used to aid research in electron and neutron acceleration, and potentially aid scientists in the creation of new substances and elements.","F=ma Force=mass (acceleration) F=qE Therefore, this inventive device can help scientists change the acceleration or deceleration of electrons.","The magnetic field created when an electron, proton or neutron, of an atom can be changed after passing through this vortex effect.","Therefore, even a radioactive isotope could be altered from this vortex effect.","In an electron application, this could be constructed on a smaller scale to a vacuum chamber and a free electron would be accelerated with a laser and a gas (most likely xenon) can be pressurized and sent through a heat resistant alloy gas manifold to the nozzle ports.","Such that, the free electron passes through the tubular cylinder, with a laser (thermal energy) providing the dynamic pressure for the cylinder.","Now as the electron passes through my invention it would gain velocity from a thermal vortex effect and would simulate fusion as an energy source.","The electron would gain enormous speed as it passed through the thermal vortex effect cylinder.","For this application the tubular cylinder would have to be made of a super heat resistant alloy and incorporate a low level electro-magnetic field to further impact the acceleration through the vortex effect.","Pressurized air was utilized to create this vortex effect, however, any pressurized gas, liquid or solid could be substituted to create a change in the dynamic pressure of the vacuum column.","For example, pressurized hydraulic fluid, food grade cooking oil, or even some of the product being transported could also be utilized to create a vortex effect on the vacuum column.","Another example would be to use pressurized water in lieu of compressed air to create a vortex effect.","The number of holes can be varied depending on the acceleration rate desired.","Another variable is the size of the orifice or hole that will change the acceleration rate as well as the number of holes in the tube that pressurized air is being introduced to.","In my model, I utilized ½ inch diameter holes with half inch airline and utilizes a variable air flow valve to control the flow of air and the orifice size and the deflection angle of the pressurized air hitting the inside sidewall of the cylinder and or tube controls the air and material speed of the accelerator and the inlet air pressure can all be adjusted to increase or decrease the speed of the materials through the pipe.","Inlet air pressures and volumes of air can be adjusted to infinitely vary speed and achieve the desired reduction in friction and effective gravity on the material conveyed or being vacuumed i.e.","Example negative pressure.","The pressurized air when introduced to our cylinder creates a vortex effect inside the cylinder pipe that pulls material from one side of the cylinder and spins it out the opposite side with force.","This effect works if the pipe is in a vertical, horizontal or any plane in between.","When negative pressure is introduced to the push side of the vacuum accelerator something totally fascinating occurs.","The frictional drag of material whether it is water, sludge, or aggregate or any mixture thereof in between on the cylinder is decreased and the effective weight of material in the material is decreased.","Therefore, this translates into the material in the vacuum column to move at a faster rate with the vacuum system be it positive displacement blower or vein pump or any vacuum system drive.","The vacuum accelerator accelerates the material speed and aids moving any type of material in a pipe or tubular application.","The vacuum accelerator reduces the energy required to move material.","The energy savings can be substantial.","In a blower application the use of a vacuum accelerator can provide many benefits, for example: a vacuum accelerator can aid in moving material a longer distance than a blower system is currently capable of moving.","In one test, we were able to convey material eight hundred feet through an eight-inch pipe by clamping two vacuum accelerators in line on a horizontal pull.","Another great benefit of a vacuum accelerator is increasing the speed of loading material through a pipe.","Still another benefit is the increase in negative pressure or vacuum with all other item constant which will translate in significant energy costs reductions and fuel savings for combustible fuel engines or electrical energy savings through reduced horsepower requirements.","When a blower, vein or vacuum system is attached to a vacuum accelerator, the system shall require less energy to perform the same amount of work.","Therefore, saving can also be realized by utilizing smaller engines and motors to preform vacuum work.","Saving can be realized by the consumption of less fuel and energy by allowing the vacuum system to perform at less RPM revolutions per minute, saving component life on the systems as well.","The Vacuum Accelerator, shall be a very cost-efficient unit.","When a negative pressure vacuum system is applied to a vacuum accelerator the multiple reductions in energy is achieved by reducing the energy required on the vacuum system to preform work.","Also, when a vacuum accelerator is applied to a centrifugal or centrifical compressor or any air conveyance system a vacuum accelerator works in the same accord, just at a different ratio.","In an air conveyance system, a vacuum accelerator aids in the reduction of frictional drag and reducing the natural force of gravity on the material being conveyed.","This in turn, reduces the amount of energy required to move material through any pipe or cylindrical application to convey material.","In this case the vacuum accelerator is placed into line with the air conveyance column; the vacuum accelerator shall help the air conveyance system move material faster and with less energy than an air conveyance system without a vacuum accelerator.","In this instance our unit actually becomes an air conveyance accelerator.","The inverse is also true that if you turn the unit around and swap ends the unit becomes an air conveyance decelerator or a vacuum system decelerator by simply putting the opposite end of the pipe to the existing system.","Therefore, this unit will also work to slow the material speed down if that is the effect desired.","Another field-tested benefit of a vacuum accelerator is to reduce the time required to perform a vacuum job or to reduce the time to perform an air conveyance job of material or liquids.","Typical applications shall be in vacuum of materials such as sewer, storm line and sludge debris and hazard materials vacuum systems that move aggregates and sludge.","Street sweeper vacuum, air conveyance and regenerative air conveyance systems to reduce horsepower demands and fuel consumption, are examples.","The Vacuum accelerators can be used to move more material at a faster rate into a debris body on a street sweeper or environmental conveyance vehicle.","Another application is to use vacuum accelerators in industrial plants to move liquids and solids, in plant lines to reduce energy costs and to speed the vacuum column of material from one point to another are it in a horizontal, vertical plane or any combination in between.","Another application is to use a vacuum accelerator in a lift station application to aid a lift station pump to move material in a force main and to move material into and from a treatment plant and or water or canal distribution plant.","The power to move material into and from treatment plants is costly, many times employing high voltage (4160 volt) large motor driven electric generators that drive very large positive displacement blowers.","A vacuum accelerator in line would decrease the energy required (start-up torque) and the energy required to maintain (running torque) of large blower systems.","These units might be 36 inches to 72 inches in diameter depending on the system.","The principle would be the same to reduce the amount of energy required to move liquids and aggregates through a column.","Another application would be in fuel injection systems for automobiles.","As we know electronic fuel injector systems electronically sense when to open and close to create base pulse width based on load and rpm.","A vacuum accelerator would allow less fuel to be required for combustion as through the vortex effect a larger percentage of the liquid gas would be converted to a gaseous state, thereby decrease the pulse width required for an equivalent amount of combustion.","Also, the velocity created would enhance combustion as well.","These vacuum accelerators could be very small in size for example an eighth of an inch in diameter or smaller and installed in line into each injector system to decrease the amount of fuel required for combustion.","A portion of the exhaust gas could be recycled and used as the air power source to create the vortex effect, there-by, reducing emissions while improving fuel economy simultaneously.","In diesel engine applications a vacuum accelerator could be used in a direct injection system to move evenly circulate the diesel mist inside a cylinder to achieve improved combustion with a decreased amount of fuel.","As the vortex effect would allow more efficient mixing and a larger percentage of gaseous diesels as opposed to liquid diesel thereby aiding combustion with decreased amounts of actual fuel.","Exhaust air can be the supply force or a mixture of exhaust and intake air, by recycling the exhaust air stream two advantages are gained, the heated air stream aids combustibility and reduces emissions while aiding fuel efficiency.","Another application relates to CNG gas transfer.","One problem exists in the field of high pressure gas transfer.","Currently, the methods are fast fill at around 3600 psi or up to 4300 psi and higher and slow fill at 3000 psi.","Either method has its advantages and disadvantages in fill efficiency.","Fast fill is approximately equal in the time required to liquid fill a tank and slow fill takes several hours, but fills the tanks to a greater volume.","My invention shall reduce the time to fill the receiving tank in either situation.","The other benefit is that the tanks shall fill with greater volume.","The filling line is connected to one end of the vacuum accelerator via a high-pressure gas fitting.","The opposite end is attached to the receiving tank.","The supply hose for the vacuum accelerator is this case is attached to a lower pressure CNG fill tank.","As the lower pressure gas enters the accelerator this causes a low-pressure area at the receiving tank inlet, increasing the differential pressure, which in turn causes the tank to fill more rapidly.","An external cooler can be applied to the accelerator that actually lowers the temperature of the CNG gas and thus causes the receiving tank to fill to greater volume capacity as it decreases the expansion rate of the gas.","The end result is that the receiving tanks are filled more efficiently.","Another application relates to increasing propulsion efficiency by decreasing residual kinetic energy via a vacuum accelerator attached to air breathing jet engine.","N(Overall energy efficiency)=Np(Propulsion Efficiency)×Nve(Cycle Efficiency) Therefore; for jet engines the propulsive efficiency is highest when the jet engine emits an exhaust jet at a velocity that is the same as, or nearly the same as, the vehicle speed as this gives the smallest residual kinetic energy.","The formula for air breathing engines moving at speed v with an exhaust velocity Ve is given: Np ( Propulsion Efficiency ) = 2 1 + Ve / v The invention shall be attached to the end of the jet nozzle and the unit shall increase propulsion efficiency by lowering the residual kinetic energy.","The vacuum decelerator shall slow the exhaust velocity thru its vortex effect when propulsion is required and the vacuum shall accelerate when the exhaust velocity needs to increase to reduce propulsion rapidly.","The invention not only improves propulsion efficiency, it also is an excellent safety device that allows the pilot to vary his deceleration without causing stall.","In addition, normal air fuel ratios of 50:1 rich to 130:1 weak limit vary depending on take-off, cruise and altitude, but because the invention reduces residual kinetic energy as exhaust velocity jet approaches velocity, significant fuel saving are achieved, and overall propulsion efficiency is optimized.","My invention was also applied to an air conveyance system, and my invention changes the air velocity of an air conveyance column as well.","In an electron application my invention would be constructed on a smaller scale to a vacuum chamber and a free electron would be accelerated with a laser and a gas most likely xenon can be pressurized and sent through a heat resistant alloy gas manifold to the nozzle ports, such that the free electron passes through the tubular cylinder, with a laser (thermal energy) providing the dynamic pressure for the cylinder.","Now as the electron passes through my invention it would gain velocity from a thermal vortex effect and would simulate fusion as an energy source.","Although specific applications and or embodiments of the invention have been described with reference to the drawing are by way of examples only and merely illustrate some of the many possible specific applications embodiments which represent application of the principles of the invention.","Various changes, manipulations and/or obvious modifications to one skilled in the art to which the invention pertains are deemed to be within the scope, the spirit, essence, and contemplation of the invention as further defined within the following claims."]],"string":"[\n [\n \"METHOD FOR IMPROVED TRANSPORT OF MATERIALS THROUGH A PIPE, TUBE OR CYLINDER STRUCTURE USING A VORTEX EFFECT PRODUCTION DEVICE\",\n \"A tubular or cylindrical unit that creates a vortex effect with externally supplied pressurized fluid injected angularly within a transport structure is provided.\",\n \"Such a unit is utilized to either accelerate the vacuum and/or air conveyance of liquids, solid aggregates, and gases, reduce the energy required for such materials transport processes, or both.\",\n \"Such a result is achieved through the introduction of pressurized fluid via a plurality of injectors situated evenly around the circumference of the subject tube, pipe, and/or cylinder, and angled uniformly for an even pressure injection of fluid within the conveyance component thereof.\",\n \"In effect, through such injection of pressurized fluid, the overall transport system may be operated at significantly reduced cost while increasing the efficiency of overall vacuum and air conveyance systems simultaneously.\",\n \"The method of utilization of such a device is also encompassed within this invention.\"\n ],\n [\n \"1.A method of providing materials transport, said method comprising the steps of: a) providing a materials transport device including a cylinder, pipe, and/or tube conveyance component having an external portion and an internal portion, both measuring the same length and sharing the same first end and same opposing second end, wherein said conveyance component comprises at least three injectors substantially evenly spaced circumferentially around said external portion and substantially evenly spaced at differing locations along said length of said external portion, said at least three injectors providing internal introduction of forced fluids angularly within the internal portion of said conveyance component, wherein said injectors are aligned to provide uniform angles of fluid introduction within said conveyance component internal portion, and wherein said uniform angles of fluid introduction create a vortex effect within said conveyance component upon uniform introduction of fluid or gas materials within said injectors such that said vortex effect creates vacuum acceleration in one direction and vacuum deceleration in the reverse direction; b) introducing a material for transport within said transport device and said fluid or gas materials within said at least three injectors; and c) creating a vortex effect within said transport device upon gas or fluid movement from said injectors within said transport device, thereby forcing said material for transport to move within said transport device.\",\n \"2.The method of providing materials transport of claim 1 wherein said materials transport device further including a fluid source component that is connected separately to each injector, thereby introducing the same pressure and velocity fluid within the conveyance component internal portion during operation.\",\n \"3.The method of providing materials transport of claim 1 wherein said material transport device is in the form of a solids transport structure, a liquid transport structure, or a gas transport structure.\",\n \"4.The method of providing materials transport of claim 2 wherein said material transport device is in the form of a solids transport structure, a liquid transport structure, or a gas transport structure.\",\n \"5.The method of providing materials transport of claim 1 wherein said material transport device is provided in the form of a valve-like structure, a vacuum-assisted structure, or an air or liquid conveyance structure.\",\n \"6.The method of providing materials transport of claim 2 wherein said material transport device is provided in the form of a valve-like structure, a vacuum-assisted structure, or an air or liquid conveyance structure.\"\n ],\n [\n \" BACKGROUND OF THE INVENTION Transport of materials, whether liquids, solids, and even gases, has been of enormous importance for a myriad of reasons.\",\n \"Whether necessary for removal purposes, introduction within and at certain locations, or other similar situations that utilize a horizontal operation, such activities have proven valuable for various economic bases.\",\n \"Typically, such material movement through vertical and/or horizontal pipes and tubes requires a significant amount of energy from vacuum and air conveyance systems due to gravity effects, laminar flow limitations, and conveyance speed requirements, at least.\",\n \"In terms of vacuum systems, air conveyance can only transport materials a certain distance and at a certain maximum loading speed, dependent on a number of factors, such as material weight, material density, and pipe or tube diameter.\",\n \"Dynamic pressure through such devices are measurable, at least in terms of fluid dynamics, by the equation: in-line-formulae description=\\\"In-line Formulae\\\" end=\\\"lead\\\"?\",\n \"q= ½ p*v 2 in-line-formulae description=\\\"In-line Formulae\\\" end=\\\"tail\\\"?\",\n \"wherein q is dynamic pressure measured in Pascals, p is fluid density, and v is velocity through the device.\",\n \"Such dynamic pressure is equal to the difference between stagnation pressure and static pressure.\",\n \"There is thus a need to provide an effective change in such dynamic pressure measurements within a vacuum column (or air conveyance system) in order to provide greater efficiencies.\",\n \"To that end, as is stated in the conservation of energy theorem, energy is constant and neither created nor destroyed, just changed in terms of form.\",\n \"Thus, for instance, energy from air (or other introduced gas) exhibits a pressure stream that angularly strikes the pipe/tube/cylinder wall and modifies the dynamic pressure of the vacuum column during operation.\",\n \"Such changes effectively evince reductions in energy to move materials in such devices as a result.\",\n \"The problem, however, remains that the energy required for such vacuum pressure applications is significant for any such effect.\",\n \"There thus exists a need to provide improvements in materials transport through such pipe/tube systems, particularly in terms of reducing the energy necessary to undertake such a task without appreciably decreasing materials transport rates (or transversely, increasing such rates with similar energy output measurements).\",\n \"To date, such has not been effectively provided within the pertinent industries.\",\n \"For instance, vacuum devices are standard to allow for such transport from a certain desired location.\",\n \"Although such devices may provide a relatively effective means for conveyance in these situations, the energy required for operation, particularly if the materials are of, again, significant weight and/or density, and if the pipe/tube is of a limited diameter, can be extremely high.\",\n \"A means to permit more effective movement through the selected tube/pipe in conjunction with a vacuum system would be highly prized, specifically with the reduced need for vacuum strength for the overall desired effect.\",\n \"Thus, for instance, vacuum systems for the removal of waste from various locations (such as street sweepers, septic tank cleaners, and the like), as well as solid particulate transporters (such as for, for instance, fertilizer, salt, silicon dioxide, and the like, movement devices) for manufacturing or other like operations, and even within mechanical valve-like devices (such as synthetic heart valves, for instance), all suffer from the same associated limitations.\",\n \"Although some transport to and through such devices may be accomplished to a certain degree, their effectiveness has proven compromised when coupled to the necessary energy generation needed for operation and/or the valves themselves lack the needed effective transport result at the rate and in the same manner as is necessary for proper actions within the selected milieu.\",\n \"Likewise, in situations where air conveyance (or other type of forwardly forced material movement) is undertaken, the energy levels needed can be excessive for effective results.\",\n \"Additionally, the forced air operation may face significant difficulties in terms of laminar flow through the selected pipe/tube due to turbulence and density of the materials themselves.\",\n \"Continued forced air may result, for instance, in uneven packing of solids and inner surface adhesion for liquids (as well as potential turbulence with gases).\",\n \"This uneven action may also result in uneven blending of materials during transport in certain circumstances that may prove deleterious for the overall operation, as well.\",\n \"In any event, there exists a great need to provide improved materials transport potential with increased efficiency of vacuum and air conveyance systems in terms of both/either energy levels needed for effective transport and/or faster transport times with lower energy levels required.\",\n \"Additionally, a device and/or method that allows for more effective blending of transported materials in such a situation would also be desirable in some situations.\",\n \"To date, however, such a system or systems has yet to be provided the pertinent industries that meet such improved energy output levels, at least.\"\n ],\n [\n \" ADVANTAGES AND SUMMARY OF THE INVENTION Thus, one significant advantage of the present invention is the ability to reduce dynamic pressures within a conveyance tube/pipe with energy levels far lower than for typical air or vacuum conveyance applications.\",\n \"Another advantage is the ability to utilize such a structure within any type of material conveyance application utilization a tube/pipe/cylinder device.\",\n \"Yet another advantage of the inventive system is the ability to reduce ineffective and deleterious turbulence within the subject pipe/tube/cylinder thereby allowing not only faster materials transport but also more effective blending of introduced materials therein during transport.\",\n \"Accordingly, the invention encompasses a materials transport device including a cylinder, pipe, and/or tube conveyance component having an external portion and an internal portion, wherein said conveyance component includes at least two (preferably three or more) injectors providing internal introduction of forced fluids angularly within the internal portion of said conveyance component, wherein said injectors are aligned to provide similar angles of fluid introduction within said conveyance component internal portion, and wherein said injectors are housed on the external portion of said conveyance component.\",\n \"Also encompassed within this invention is the materials transport device as noted above and including fluid source component that is connected separately to each injector, thereby introducing the same pressure and velocity fluid within the conveyance component internal portion during operation.\",\n \"Further encompassed within this invention is a method of providing materials transport utilizing the transport device as described above.\",\n \"As well, the transport device provided in the form of a solids transport, a liquid transport, a gas transport, and in the form of a valve-like structure, vacuum-assisted structure, and/or air or liquid conveyance structure, is also encompassed herein.\",\n \"In essence, the overall inventive transport device is one that allows for more efficient materials transport through the utilization of the plurality of injectors introducing similar and simultaneously introduced fluids within the internal portion of the conveyance component thereof.\",\n \"In this manner, the term fluids is intended to include, without limitation, a liquid, a gas, or mixtures and/or combinations of multiple liquids, multiple gases, or both gases and liquids.\",\n \"Such a result is achieved through the introduction of pressurized fluid via a plurality of injectors situated evenly around the circumference of the subject tube, pipe, and/or cylinder, and angled uniformly (at any angle that aims into the internal portion of the conveyance component of the device; a range of from 1 to 75°, with from 5 to 45° more preferred, and from about 10 to 30° potentially most preferred) for an even pressure injection of fluid within the conveyance component thereof.\",\n \"The injection of such fluids at specified angles and at selected pressures and/or velocities allows for the internal generation of a vortex effect within the conveyance component which, in turn, increases the speed of materials transport, reduces turbulence (and thus dynamic pressures) within the device, and, overall, allows for energy reductions in terms of assisting air or liquid conveyance or vacuum device utilization for such transport purposes through the overall device.\",\n \"Whether horizontally or vertically aligned, and whether such a line includes both horizontal and vertical configurations to allow transport from one location to another, the inclusion of such a plurality of injectors for such a purpose has proven effective for such improved transport results.\",\n \"In effect, the inventive materials transport device includes the conveyance component that changes the dynamic pressure of the vacuum column therein through the creation of a vortex effect caused when the introduced pressurized air angularly strikes the tubular cylinder wall.\",\n \"Such a result effectively modifies the atmospheric pressure inside the tubular cylinder, thus allowing the vortex effect to modify the internal differential pressure.\",\n \"The versatile nature of such a configuration is shown as typical vacuum systems, fuel injector systems (for automated vehicles, for instance), air conveyance devices, and even synthetic heart valves (that provide a vortex effect that is the normal action of natural heart valve structures; typical mechanical valves do not accord such prized and “natural” effects, thus leading to the inventive valve devices discussed herein according far better results for typical human circulatory/vascular system actions).\",\n \"Additionally, in terms of, for instance, fuel injector systems, the ability to utilize overflow fuel as the base injected fluid not only improves overall effectiveness and efficiency of the overall device from a energy level standpoint, but also in terms of reduction of “waste” fuel as the potential exists for far more fuel to be actually utilized within the overall activity than for typical, standard fuel injections systems utilized today.\",\n \"As such, as noted above, this multiple injector vortex production effect thus permits a relatively simple add-on to standard materials transport systems (such as the removal of a tubing component and replacement with one including the multi-injector structure included) to permit production of such an effective energy reduction result.\",\n \"In other respects, the system may include the addition or inclusion of a blower, vein, or vacuum system attached to a base vacuum accelerator, as well.\",\n \"Such an overall configuration utilizing the inventive device requires less energy to perform the same amount of work of materials transport as without.\",\n \"In such situations, then, significant savings can also be realized by utilizing smaller engines and motors to perform standard vacuum activities without losing any effectiveness.\",\n \"The ability to reduce the overall engine size to this degree may result in the consumption of less fuel and energy since the engine can run at full effectiveness but at fewer revolutions per minute, thereby also saving component life on the systems as well.\",\n \"Furthermore, the utilization of a vacuum accelerator with the inventive device can allow for the application of a negative pressure vacuum system thereto, permitting multiple reductions in energy since the base vacuum does not require increased energy levels for full capacity in performance.\",\n \"Additionally, the application of such a vacuum accelerator to a centrifugal or centrifical compressor (or any air conveyance system, for that matter), the vacuum accelerator can function in a similar manner, albeit at a different work ratio.\",\n \"In such air conveyance systems, in other words, the added vacuum accelerator aids in reducing frictional drag within the transport device and consequently aids to reduce the natural force of gravity on the conveyed material, as well.\",\n \"This capability then permits an overall reduction in the amount of energy required to move such conveyed materials through any applied transport pipe or cylinder.\",\n \"In one example, then, a vacuum accelerator may be placed in line with an air conveyance column; the resultant vacuum accelerator helps the air conveyance system move material faster and with less energy than an air conveyance system without a vacuum accelerator, ostensibly modifying the system into an air conveyance accelerator.\",\n \"Another application of the inventive device may be the utilization of such a vacuum accelerator within industrial plants in order to move liquids and solids in plant lines at reduced energy costs and at higher velocities.\",\n \"As it applies to horizontal, vertical, or even diagonal transport lines, such a device helps achieve greater efficiencies as noted above.\",\n \"Furthermore, such a device may be utilized to alter or mix substances for industrial and food service applications.\",\n \"As above, such is achieved through the introduction of the pressurized fluid via the plurality of injectors situated evenly around the circumference of the subject tube, pipe, and/or cylinder, and angled uniformly for an even pressure injection of fluid within the conveyance component thereof.\",\n \"Added to such a device, then, is the ability, for instance, to create an effective and thorough mixing result during transport of materials through the generation of such a vortex effect.\",\n \"Coupled to such a potential operation could be variations in temperatures (external to internal, for instance); if such temperatures are varied in such a respect, the transport device could effective heat or cool the transported materials, permitting not only thorough mixing, but possible modifications in the substances themselves.\",\n \"Again, this permits not only a reduction in energy for transport purposes, but the potential for reduced energy requirements for mixing as well, thereby increasing the overall effectiveness and efficiency of the entire system.\",\n \"In one non-limiting example, with ice cream raw materials passed through the inventive device, the mixing and efficiency of moving and condensing the end product consistency could be greatly improved.\",\n \"With the natural formation of an electro-magnetic field when kinetic energy is transformed into dynamic pressure, there further exists the potential for improved blending of such substances passing through the vortex effect at a molecular level, too.\",\n \"Such a result could occur at a particle basis after passing through the produced vortex since it could also be (theoretically) super-heated or super cooled through temperature controls.\",\n \"Such blending benefits could thus also aid in the medical and chemical fields, respectively, particularly to blend substances into compounds.\",\n \"Another application in the medical field would be in the blending of medicines for the human body, particularly as this device permits such mixing, again, while being transported, rather than prior to or after such a blending step.\",\n \"One particularly effective application for the inventive device is medically based in terms of synthetic valves for the human heart.\",\n \"Blood flow into and from the human heart is accomplished through certain valves that are known to create a natural vortex effect that spins off negative charges.\",\n \"Artificial heart replacement valves do not provide similar effects, thus limiting the effectiveness of such synthetic structures.\",\n \"For instance, if such an artificial valve could spin off negative charges in the left ventricle, optimal blood transport results could be realized.\",\n \"Unfortunately, such is not the case, and the standard artificial valves create far reduced levels of blood flow within the patient's body.\",\n \"The present invention can be properly sized and configured to utilize blood as the injected fluid and could be utilized as a more efficient artificial human heart replacement valve that more closely simulates the actual human circulatory system.\",\n \"In comparison with standard artificial heart valves, the inventive device could also reduce clotting and other undesirable factors, as well.\",\n \"In terms of production particulars, as examples, a vacuum accelerator materials transport device of the present invention may be constructed of a variety of materials such as steel, abrasion resistant steel, extend steel, corten steel, polyvinyl chloride, plastic resin, glass, all forms of stainless or precious metals, aluminum, alloys, copper, bronze, and the like (including any combinations thereof).\",\n \"For production purposes, a manufacturer would typically start with a tube or cylindrical shaped structure and add flanges thereto.\",\n \"These flanges are normally constructed of the same material as the tube.\",\n \"Flanges can be either band lock, flat flange, seamless, bolt able, and or weld able or clamp together flanges of any nature.\",\n \"The flanges allow for attachment to other tubes/pipes/cylinders at either end to permit reliable introduction of the conveyance component of the overall materials transport device.\",\n \"Once securely in place, the overall device may be utilized with the injectors connected to and introducing a fluid source at the necessary angles within the internal portion of the conveyance component to achieve the desired vortex effect and thus the overall improvements in materials transport efficiencies.\"\n ],\n [\n \"CROSS-REFERENCE TO RELATED APPLICATIONS This application is a divisional of and claims priority to pending U.S. patent application Ser.\",\n \"No.\",\n \"14/283,218, filed on May 21, 2014, which claims the benefit of U.S.\",\n \"Provisional Patent Application No.\",\n \"61/855,655, now expired, filed on May 20, 2013.The entirety of both parent and grand-parent applications are herein incorporated by reference.\",\n \"FIELD OF THE INVENTION A tubular or cylindrical unit that creates a vortex effect with externally supplied pressurized fluid injected angularly within a transport structure is provided.\",\n \"Such a unit is utilized to either accelerate the vacuum and/or air conveyance of liquids, solid aggregates, and gases, reduce the energy required for such materials transport processes, or both.\",\n \"Such a result is achieved through the introduction of pressurized fluid via a plurality of injectors situated evenly around the circumference of the subject tube, pipe, and/or cylinder, and angled uniformly for an even pressure injection of fluid within the conveyance component thereof.\",\n \"In effect, through such injection of pressurized fluid, the overall transport system may be operated at significantly reduced cost while increasing the efficiency of overall vacuum and air conveyance systems simultaneously.\",\n \"The method of utilization of such a device is also encompassed within this invention.\",\n \"BACKGROUND OF THE INVENTION Transport of materials, whether liquids, solids, and even gases, has been of enormous importance for a myriad of reasons.\",\n \"Whether necessary for removal purposes, introduction within and at certain locations, or other similar situations that utilize a horizontal operation, such activities have proven valuable for various economic bases.\",\n \"Typically, such material movement through vertical and/or horizontal pipes and tubes requires a significant amount of energy from vacuum and air conveyance systems due to gravity effects, laminar flow limitations, and conveyance speed requirements, at least.\",\n \"In terms of vacuum systems, air conveyance can only transport materials a certain distance and at a certain maximum loading speed, dependent on a number of factors, such as material weight, material density, and pipe or tube diameter.\",\n \"Dynamic pressure through such devices are measurable, at least in terms of fluid dynamics, by the equation: q=½p*v2 wherein q is dynamic pressure measured in Pascals, p is fluid density, and v is velocity through the device.\",\n \"Such dynamic pressure is equal to the difference between stagnation pressure and static pressure.\",\n \"There is thus a need to provide an effective change in such dynamic pressure measurements within a vacuum column (or air conveyance system) in order to provide greater efficiencies.\",\n \"To that end, as is stated in the conservation of energy theorem, energy is constant and neither created nor destroyed, just changed in terms of form.\",\n \"Thus, for instance, energy from air (or other introduced gas) exhibits a pressure stream that angularly strikes the pipe/tube/cylinder wall and modifies the dynamic pressure of the vacuum column during operation.\",\n \"Such changes effectively evince reductions in energy to move materials in such devices as a result.\",\n \"The problem, however, remains that the energy required for such vacuum pressure applications is significant for any such effect.\",\n \"There thus exists a need to provide improvements in materials transport through such pipe/tube systems, particularly in terms of reducing the energy necessary to undertake such a task without appreciably decreasing materials transport rates (or transversely, increasing such rates with similar energy output measurements).\",\n \"To date, such has not been effectively provided within the pertinent industries.\",\n \"For instance, vacuum devices are standard to allow for such transport from a certain desired location.\",\n \"Although such devices may provide a relatively effective means for conveyance in these situations, the energy required for operation, particularly if the materials are of, again, significant weight and/or density, and if the pipe/tube is of a limited diameter, can be extremely high.\",\n \"A means to permit more effective movement through the selected tube/pipe in conjunction with a vacuum system would be highly prized, specifically with the reduced need for vacuum strength for the overall desired effect.\",\n \"Thus, for instance, vacuum systems for the removal of waste from various locations (such as street sweepers, septic tank cleaners, and the like), as well as solid particulate transporters (such as for, for instance, fertilizer, salt, silicon dioxide, and the like, movement devices) for manufacturing or other like operations, and even within mechanical valve-like devices (such as synthetic heart valves, for instance), all suffer from the same associated limitations.\",\n \"Although some transport to and through such devices may be accomplished to a certain degree, their effectiveness has proven compromised when coupled to the necessary energy generation needed for operation and/or the valves themselves lack the needed effective transport result at the rate and in the same manner as is necessary for proper actions within the selected milieu.\",\n \"Likewise, in situations where air conveyance (or other type of forwardly forced material movement) is undertaken, the energy levels needed can be excessive for effective results.\",\n \"Additionally, the forced air operation may face significant difficulties in terms of laminar flow through the selected pipe/tube due to turbulence and density of the materials themselves.\",\n \"Continued forced air may result, for instance, in uneven packing of solids and inner surface adhesion for liquids (as well as potential turbulence with gases).\",\n \"This uneven action may also result in uneven blending of materials during transport in certain circumstances that may prove deleterious for the overall operation, as well.\",\n \"In any event, there exists a great need to provide improved materials transport potential with increased efficiency of vacuum and air conveyance systems in terms of both/either energy levels needed for effective transport and/or faster transport times with lower energy levels required.\",\n \"Additionally, a device and/or method that allows for more effective blending of transported materials in such a situation would also be desirable in some situations.\",\n \"To date, however, such a system or systems has yet to be provided the pertinent industries that meet such improved energy output levels, at least.\",\n \"ADVANTAGES AND SUMMARY OF THE INVENTION Thus, one significant advantage of the present invention is the ability to reduce dynamic pressures within a conveyance tube/pipe with energy levels far lower than for typical air or vacuum conveyance applications.\",\n \"Another advantage is the ability to utilize such a structure within any type of material conveyance application utilization a tube/pipe/cylinder device.\",\n \"Yet another advantage of the inventive system is the ability to reduce ineffective and deleterious turbulence within the subject pipe/tube/cylinder thereby allowing not only faster materials transport but also more effective blending of introduced materials therein during transport.\",\n \"Accordingly, the invention encompasses a materials transport device including a cylinder, pipe, and/or tube conveyance component having an external portion and an internal portion, wherein said conveyance component includes at least two (preferably three or more) injectors providing internal introduction of forced fluids angularly within the internal portion of said conveyance component, wherein said injectors are aligned to provide similar angles of fluid introduction within said conveyance component internal portion, and wherein said injectors are housed on the external portion of said conveyance component.\",\n \"Also encompassed within this invention is the materials transport device as noted above and including fluid source component that is connected separately to each injector, thereby introducing the same pressure and velocity fluid within the conveyance component internal portion during operation.\",\n \"Further encompassed within this invention is a method of providing materials transport utilizing the transport device as described above.\",\n \"As well, the transport device provided in the form of a solids transport, a liquid transport, a gas transport, and in the form of a valve-like structure, vacuum-assisted structure, and/or air or liquid conveyance structure, is also encompassed herein.\",\n \"In essence, the overall inventive transport device is one that allows for more efficient materials transport through the utilization of the plurality of injectors introducing similar and simultaneously introduced fluids within the internal portion of the conveyance component thereof.\",\n \"In this manner, the term fluids is intended to include, without limitation, a liquid, a gas, or mixtures and/or combinations of multiple liquids, multiple gases, or both gases and liquids.\",\n \"Such a result is achieved through the introduction of pressurized fluid via a plurality of injectors situated evenly around the circumference of the subject tube, pipe, and/or cylinder, and angled uniformly (at any angle that aims into the internal portion of the conveyance component of the device; a range of from 1 to 75°, with from 5 to 45° more preferred, and from about 10 to 30° potentially most preferred) for an even pressure injection of fluid within the conveyance component thereof.\",\n \"The injection of such fluids at specified angles and at selected pressures and/or velocities allows for the internal generation of a vortex effect within the conveyance component which, in turn, increases the speed of materials transport, reduces turbulence (and thus dynamic pressures) within the device, and, overall, allows for energy reductions in terms of assisting air or liquid conveyance or vacuum device utilization for such transport purposes through the overall device.\",\n \"Whether horizontally or vertically aligned, and whether such a line includes both horizontal and vertical configurations to allow transport from one location to another, the inclusion of such a plurality of injectors for such a purpose has proven effective for such improved transport results.\",\n \"In effect, the inventive materials transport device includes the conveyance component that changes the dynamic pressure of the vacuum column therein through the creation of a vortex effect caused when the introduced pressurized air angularly strikes the tubular cylinder wall.\",\n \"Such a result effectively modifies the atmospheric pressure inside the tubular cylinder, thus allowing the vortex effect to modify the internal differential pressure.\",\n \"The versatile nature of such a configuration is shown as typical vacuum systems, fuel injector systems (for automated vehicles, for instance), air conveyance devices, and even synthetic heart valves (that provide a vortex effect that is the normal action of natural heart valve structures; typical mechanical valves do not accord such prized and “natural” effects, thus leading to the inventive valve devices discussed herein according far better results for typical human circulatory/vascular system actions).\",\n \"Additionally, in terms of, for instance, fuel injector systems, the ability to utilize overflow fuel as the base injected fluid not only improves overall effectiveness and efficiency of the overall device from a energy level standpoint, but also in terms of reduction of “waste” fuel as the potential exists for far more fuel to be actually utilized within the overall activity than for typical, standard fuel injections systems utilized today.\",\n \"As such, as noted above, this multiple injector vortex production effect thus permits a relatively simple add-on to standard materials transport systems (such as the removal of a tubing component and replacement with one including the multi-injector structure included) to permit production of such an effective energy reduction result.\",\n \"In other respects, the system may include the addition or inclusion of a blower, vein, or vacuum system attached to a base vacuum accelerator, as well.\",\n \"Such an overall configuration utilizing the inventive device requires less energy to perform the same amount of work of materials transport as without.\",\n \"In such situations, then, significant savings can also be realized by utilizing smaller engines and motors to perform standard vacuum activities without losing any effectiveness.\",\n \"The ability to reduce the overall engine size to this degree may result in the consumption of less fuel and energy since the engine can run at full effectiveness but at fewer revolutions per minute, thereby also saving component life on the systems as well.\",\n \"Furthermore, the utilization of a vacuum accelerator with the inventive device can allow for the application of a negative pressure vacuum system thereto, permitting multiple reductions in energy since the base vacuum does not require increased energy levels for full capacity in performance.\",\n \"Additionally, the application of such a vacuum accelerator to a centrifugal or centrifical compressor (or any air conveyance system, for that matter), the vacuum accelerator can function in a similar manner, albeit at a different work ratio.\",\n \"In such air conveyance systems, in other words, the added vacuum accelerator aids in reducing frictional drag within the transport device and consequently aids to reduce the natural force of gravity on the conveyed material, as well.\",\n \"This capability then permits an overall reduction in the amount of energy required to move such conveyed materials through any applied transport pipe or cylinder.\",\n \"In one example, then, a vacuum accelerator may be placed in line with an air conveyance column; the resultant vacuum accelerator helps the air conveyance system move material faster and with less energy than an air conveyance system without a vacuum accelerator, ostensibly modifying the system into an air conveyance accelerator.\",\n \"Another application of the inventive device may be the utilization of such a vacuum accelerator within industrial plants in order to move liquids and solids in plant lines at reduced energy costs and at higher velocities.\",\n \"As it applies to horizontal, vertical, or even diagonal transport lines, such a device helps achieve greater efficiencies as noted above.\",\n \"Furthermore, such a device may be utilized to alter or mix substances for industrial and food service applications.\",\n \"As above, such is achieved through the introduction of the pressurized fluid via the plurality of injectors situated evenly around the circumference of the subject tube, pipe, and/or cylinder, and angled uniformly for an even pressure injection of fluid within the conveyance component thereof.\",\n \"Added to such a device, then, is the ability, for instance, to create an effective and thorough mixing result during transport of materials through the generation of such a vortex effect.\",\n \"Coupled to such a potential operation could be variations in temperatures (external to internal, for instance); if such temperatures are varied in such a respect, the transport device could effective heat or cool the transported materials, permitting not only thorough mixing, but possible modifications in the substances themselves.\",\n \"Again, this permits not only a reduction in energy for transport purposes, but the potential for reduced energy requirements for mixing as well, thereby increasing the overall effectiveness and efficiency of the entire system.\",\n \"In one non-limiting example, with ice cream raw materials passed through the inventive device, the mixing and efficiency of moving and condensing the end product consistency could be greatly improved.\",\n \"With the natural formation of an electro-magnetic field when kinetic energy is transformed into dynamic pressure, there further exists the potential for improved blending of such substances passing through the vortex effect at a molecular level, too.\",\n \"Such a result could occur at a particle basis after passing through the produced vortex since it could also be (theoretically) super-heated or super cooled through temperature controls.\",\n \"Such blending benefits could thus also aid in the medical and chemical fields, respectively, particularly to blend substances into compounds.\",\n \"Another application in the medical field would be in the blending of medicines for the human body, particularly as this device permits such mixing, again, while being transported, rather than prior to or after such a blending step.\",\n \"One particularly effective application for the inventive device is medically based in terms of synthetic valves for the human heart.\",\n \"Blood flow into and from the human heart is accomplished through certain valves that are known to create a natural vortex effect that spins off negative charges.\",\n \"Artificial heart replacement valves do not provide similar effects, thus limiting the effectiveness of such synthetic structures.\",\n \"For instance, if such an artificial valve could spin off negative charges in the left ventricle, optimal blood transport results could be realized.\",\n \"Unfortunately, such is not the case, and the standard artificial valves create far reduced levels of blood flow within the patient's body.\",\n \"The present invention can be properly sized and configured to utilize blood as the injected fluid and could be utilized as a more efficient artificial human heart replacement valve that more closely simulates the actual human circulatory system.\",\n \"In comparison with standard artificial heart valves, the inventive device could also reduce clotting and other undesirable factors, as well.\",\n \"In terms of production particulars, as examples, a vacuum accelerator materials transport device of the present invention may be constructed of a variety of materials such as steel, abrasion resistant steel, extend steel, corten steel, polyvinyl chloride, plastic resin, glass, all forms of stainless or precious metals, aluminum, alloys, copper, bronze, and the like (including any combinations thereof).\",\n \"For production purposes, a manufacturer would typically start with a tube or cylindrical shaped structure and add flanges thereto.\",\n \"These flanges are normally constructed of the same material as the tube.\",\n \"Flanges can be either band lock, flat flange, seamless, bolt able, and or weld able or clamp together flanges of any nature.\",\n \"The flanges allow for attachment to other tubes/pipes/cylinders at either end to permit reliable introduction of the conveyance component of the overall materials transport device.\",\n \"Once securely in place, the overall device may be utilized with the injectors connected to and introducing a fluid source at the necessary angles within the internal portion of the conveyance component to achieve the desired vortex effect and thus the overall improvements in materials transport efficiencies.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS FIG.\",\n \"1 provides a top view of a large diameter (60″) pipe conveyance component of the present invention.\",\n \"FIG.\",\n \"2 shows a front view of the same pipe of FIG.\",\n \"1.FIG.\",\n \"3 shows a top perspective view of the same pipe of FIG.\",\n \"1.FIG.\",\n \"4 shows a front cross-sectional view of the conveyance component pipe of FIG.\",\n \"1.FIG.\",\n \"5 provides a top view of a small diameter (18″) pipe conveyance component of the present invention.\",\n \"FIG.\",\n \"6 shows a front view of the same pipe of FIG.\",\n \"5.FIG.\",\n \"7 shows a top perspective view of the same pipe of FIG.\",\n \"5.FIG.\",\n \"8 shows a front cross-sectional view of the conveyance component pipe of FIG.\",\n \"5.FIG.\",\n \"9 provides a top view of a band-lock pipe conveyance component of the present invention.\",\n \"FIG.\",\n \"10 shows a front view of the same pipe of FIG.\",\n \"9.FIG.\",\n \"11 shows a top perspective view of the same pipe of FIG.\",\n \"9.FIG.\",\n \"12 shows a front cross-sectional view of the conveyance component pipe of FIG.\",\n \"9.FIG.\",\n \"13 provides a top view of a vacuum/air decelerator pipe conveyance component of the present invention.\",\n \"FIG.\",\n \"14 shows a front view of the same pipe of FIG.\",\n \"13.FIG.\",\n \"15 shows a top perspective view of the same pipe of FIG.\",\n \"13.FIG.\",\n \"16 shows a front cross-sectional view of the conveyance component pipe of FIG.\",\n \"13.FIG.\",\n \"17 provides a top view of a PVC pipe conveyance component of the present invention.\",\n \"FIG.\",\n \"18 shows a top perspective view of the same pipe of FIG.\",\n \"7.FIG.\",\n \"19 shows a front cross-sectional view of the conveyance component pipe of FIG.\",\n \"17.FIG.\",\n \"20 provides a top view of an industrial air accelerator-type conveyance component of the present invention.\",\n \"FIG.\",\n \"21 shows a front view of the same pipe of FIG.\",\n \"20.FIG.\",\n \"22 shows a top perspective view of the same pipe of FIG.\",\n \"20.FIG.\",\n \"23 shows a front cross-sectional view of the conveyance component pipe of FIG.\",\n \"20.FIG.\",\n \"24 provides a top view of a high-pressure water system vacuum accelerator-type pipe conveyance component of the present invention.\",\n \"FIG.\",\n \"25 shows a front view of the same pipe of FIG.\",\n \"24.FIG.\",\n \"26 shows a top perspective view of the same pipe of FIG.\",\n \"24.FIG.\",\n \"27 shows a front cross-sectional view of the conveyance component pipe of FIG.\",\n \"24.FIG.\",\n \"28 provides a top view of a positive displacement industrial vacuum loader pipe conveyance component of the present invention.\",\n \"FIG.\",\n \"29 shows a front view of the same pipe of FIG.\",\n \"28.FIG.\",\n \"30 shows a top perspective view of the same pipe of FIG.\",\n \"28.FIG.\",\n \"31 shows a front cross-sectional view of the conveyance component pipe of FIG.\",\n \"28.FIG.\",\n \"32 provides a top view of an air-style industrial vacuum accelerator pipe conveyance component of the present invention.\",\n \"FIG.\",\n \"33 shows a front view of the same pipe of FIG.\",\n \"32.FIG.\",\n \"34 shows a top perspective view of the same pipe of FIG.\",\n \"32.FIG.\",\n \"35 shows a front cross-sectional view of the conveyance component pipe of FIG.\",\n \"32.FIG.\",\n \"36 provides a top view of a water transmission vacuum accelerator long distance transport pipe conveyance component of the present invention.\",\n \"FIG.\",\n \"37 shows a front view of the same pipe of FIG.\",\n \"36.FIG.\",\n \"38 shows a top perspective view of the same pipe of FIG.\",\n \"36.FIG.\",\n \"39 shows a front cross-sectional view of the conveyance component pipe of FIG.\",\n \"36.FIG.\",\n \"40 provides a top view of a vacuum particle accelerator/collider pipe conveyance component of the present invention.\",\n \"FIG.\",\n \"41 shows a front view of the same pipe of FIG.\",\n \"40.FIG.\",\n \"42 shows a top perspective view of the same pipe of FIG.\",\n \"40.FIG.\",\n \"43 shows a front cross-sectional view of the conveyance component pipe of FIG.\",\n \"40.FIG.\",\n \"44 provides a top view of a vacuum accelerator prosthetic heart valve pipe conveyance component of the present invention.\",\n \"FIG.\",\n \"45 shows a front view of the same pipe of FIG.\",\n \"44.FIG.\",\n \"46 shows a top perspective view of the same pipe of FIG.\",\n \"44.FIG.\",\n \"47 shows a front cross-sectional view of the conveyance component pipe of FIG.\",\n \"44.FIG.\",\n \"48 provides a top view of a fuel injector add-on pipe conveyance component of the present invention.\",\n \"FIG.\",\n \"49 shows a front view of the same pipe of FIG.\",\n \"48.FIG.\",\n \"50 shows a partial cut-away front perspective view of a fuel injector to which the inventive conveyance component of FIG.\",\n \"48 is added.\",\n \"FIG.\",\n \"51 shows a front cross-sectional view of the conveyance component pipe of FIG.\",\n \"48.FIG.\",\n \"52 is a top perspective view of the same pipe of FIG.\",\n \"48.DETAILED DESCRIPTION OF THE DRAWINGS AND PREFERRED EMBODIMENTS OF THE INVENTION Without any intention of limiting the breadth and scope of the overall inventive method, the following descriptions of the accompanying drawings provide a number of potentially preferred embodiments of the inventive overall transport improvement device.\",\n \"The accompanying FIGS.\",\n \"1-52) provided herein all pertain to different versions of conveyance components that may be utilized in conjunction with the broadly defined inventive materials transport device.\",\n \"As noted above and herein, the basic structure is a pipe, tube, or cylinder to which a plurality of injectors has been incorporated within the conveyance component from an external source and introduced for injection within the internal portion at uniform angles and evenly spaced around the circumference of the base tube, pipe, and/or cylinder.\",\n \"As well, the injectors are preferably connected simultaneously to the same fluid source in order to introduce the same fluid at the same pressure in order to generate the desired vortex effect within the conveyance component of the materials transport device.\",\n \"In order to achieve such results, the structures may be produced in the following manner, dependent, certainly, upon specific sizes of base structures as it concerns the end-use desired.\",\n \"Thus, for manufacturing purposes, one manner of achieving such conveyance components of the present invention would be within the following steps: 1.A cylindrical tube is provided made of metal or alloy made of sufficient diameter to connect to existing vacuum column with ports drilled in tube.\",\n \"2.Weld a coupling to tube.\",\n \"3.Calibrate and attach air couplings to the cylindrical tube.\",\n \"4.Attach any necessary flanges to the cylindrical tube.\",\n \"5.Attach air lines to fittings.\",\n \"6.Install an air manifold.\",\n \"7.Install a variable air valve (whether mechanical, pneumatic, electrical, electronic or hydraulically actuated, depending on the application).\",\n \"8.Connect an air supply to the manifold unit.\",\n \"9.Connect a pressure gauge to the air supply.\",\n \"10.Insert nozzles into the couplers.\",\n \"Taking these base steps in conjunction with FIGS.\",\n \"1-4, for instance, provided is a 60 inch diameter tubular cylinder 1 that is drilled for ports couplings 2 and are welded strategically to the outside cylinder wall.\",\n \"The orifice size of the port with or without nozzles can be varied as well as the angle of the port to increase or decrease the speed and efficiency of the vacuum accelerator 3.The air couplings are attached to the ports on the tubular cylinder 2.Flanges 4 are attached to the end of the tube 1 in various configurations, so that the vacuum accelerator can be attached to the vacuum or air conveyance columns.\",\n \"Air lines 5 are then attached to fittings, the air manifold 6 (4-way valve) to distribute air where needed and a separate airline for air inlet.\",\n \"The variable air valve 7 is then in place to control flow and pressure and is connected to the air supply 8.The pressure gauge 9 is then attached to monitor the overall unit.\",\n \"The nozzles 10 are then inserted within the couplers 2 to permit the injection of the gas (fluid) within the internal portion of the conveyance component of the unit.\",\n \"Viewing, then FIGS.\",\n \"5-8, the same basic structure is accorded but with a smaller (18 inch) diameter tubular cylinder 11.Such a cylinder 11 is, as above, drilled for ports couplings 12 and are welded strategically to the outside cylinder wall.\",\n \"The orifice size of the port with or without nozzles can be varied as well as the angle of the port to increase or decrease the speed and efficiency of the vacuum accelerator 13.The air couplings are attached to the ports on the tubular cylinder 12.Flanges 14 are attached to the end of the tube 11 in various configurations, so that the vacuum accelerator can be attached to the vacuum or air conveyance columns.\",\n \"Air lines 15 are then attached to fittings, the air manifold 16 (4-way valve) to distribute air where needed and a separate airline for air inlet.\",\n \"The variable air valve 17 is then in place to control flow and pressure and is connected to the air supply 18.The pressure gauge 19 is then attached to monitor the overall unit.\",\n \"The nozzles 20 are then inserted within the couplers 12 to permit the injection of the gas (fluid) within the internal portion of the conveyance component of the unit.\",\n \"FIGS.\",\n \"9-12 pertain to an even smaller (8 inch) diameter tubular cylinder 21 with a band lock flange 24.Such a cylinder 21 is, as above, drilled for ports couplings 22 and are welded strategically to the outside cylinder wall.\",\n \"The orifice size of the port with or without nozzles can be varied as well as the angle of the port to increase or decrease the speed and efficiency of the vacuum accelerator 23.The air couplings are attached to the ports on the tubular cylinder 21.The band lock flanges 24 are attached to the end of the tube 21 in various configurations, so that the vacuum accelerator can be attached to the vacuum or air conveyance columns.\",\n \"Air lines 25 are then attached to fittings, the air manifold 26 (4-way valve) to distribute air where needed and a separate airline for air inlet.\",\n \"The variable air valve 27 is then in place to control flow and pressure and is connected to the air supply 28.The pressure gauge 29 is then attached to monitor the overall unit.\",\n \"The nozzles 30 are then inserted within the couplers 22 to permit the injection of the gas (fluid) within the internal portion of the conveyance component of the unit.\",\n \"An inventive vacuum/air decelerator configuration is shown in FIGS.\",\n \"13-16 with a tubular cylinder 31.Such a cylinder 31 is, as above, drilled for ports couplings 32 and are welded strategically to the outside cylinder wall.\",\n \"The orifice size of the port with or without nozzles can be varied as well as the angle of the port to increase or decrease the speed and efficiency of the vacuum accelerator 33.The air couplings are attached to the ports on the tubular cylinder 32.Flanges 34 are attached to the end of the tube 31 in various configurations, so that the vacuum accelerator can be attached to the vacuum or air conveyance columns.\",\n \"Air lines 35 are then attached to fittings, the air manifold 36 (4-way valve) to distribute air where needed and a separate airline for air inlet.\",\n \"The variable air valve 37 is then in place to control flow and pressure and is connected to the air supply 38.The pressure gauge 39 is then attached to monitor the overall unit.\",\n \"The nozzles 40 are then inserted within the couplers 32 to permit the injection of the gas (fluid) within the internal portion of the conveyance component of the unit.\",\n \"A polyvinyl chloride application is shown in FIGS.\",\n \"17-19 with a tubular PVC cylinder 41.Such a cylinder 41 is, as above, drilled for ports couplings 42 and are welded strategically to the outside cylinder wall.\",\n \"The orifice size of the port with or without nozzles can be varied as well as the angle of the port to increase or decrease the speed and efficiency of the vacuum accelerator 43.The air couplings are attached to the ports on the tubular cylinder 42.PVC flanges 44 are attached to the end of the tube 41 in various configurations, so that the vacuum accelerator can be attached to the vacuum or air conveyance columns.\",\n \"Air lines 45 are then attached to fittings, the air manifold 46 (4-way valve) to distribute air where needed and a separate airline for air inlet.\",\n \"The variable air valve 47 is then in place to control flow and pressure and is connected to the air supply 48.The pressure gauge 49 is then attached to monitor the overall unit.\",\n \"The nozzles 50 are then inserted within the couplers 42 to permit the injection of the gas (fluid) within the internal portion of the conveyance component of the unit.\",\n \"An inventive industrial street sweeper-type regenerative air style machine air accelerator conveyance component is shown in FIGS.\",\n \"20-23 with a tubular cylinder 51.Such a cylinder 51 is, as above, drilled for ports couplings 52 and are welded strategically to the outside cylinder wall.\",\n \"The orifice size of the port with or without nozzles can be varied as well as the angle of the port to increase or decrease the speed and efficiency of the vacuum accelerator 53.The air couplings are attached to the ports on the tubular cylinder 52.Flanges 54 are attached to the end of the tube 51 in various configurations, so that the vacuum accelerator can be attached to the vacuum or air conveyance columns.\",\n \"Air lines 55 are then attached to fittings, the air manifold 56 (4-way valve) to distribute air where needed and a separate airline for air inlet.\",\n \"The variable air valve 57 is then in place to control flow and pressure and is connected to the air supply 58.The pressure gauge 59 is then attached to monitor the overall unit.\",\n \"The nozzles 60 are then inserted within the couplers 52 to permit the injection of the gas (fluid) within the internal portion of the conveyance component of the unit.\",\n \"An inventive high-pressure vacuum accelerator for, for example, water transport, is shown in FIGS.\",\n \"24-27 with a tubular cylinder 61.Such a cylinder 61 is, as above, drilled for ports couplings 62 and are welded strategically to the outside cylinder wall.\",\n \"The orifice size of the port with or without nozzles can be varied as well as the angle of the port to increase or decrease the speed and efficiency of the vacuum accelerator 63.The air couplings are attached to the ports on the tubular cylinder 62.Flanges 64 are attached to the end of the tube 61 in various configurations, so that the vacuum accelerator can be attached to the vacuum or air conveyance columns.\",\n \"Air lines 65 are then attached to fittings, the air manifold 66 (4-way valve) to distribute air where needed and a separate airline for air inlet.\",\n \"The variable air valve 67 is then in place to control flow and pressure and is connected to the air supply 68.The pressure gauge 69 is then attached to monitor the overall unit.\",\n \"The nozzles 70 are then inserted within the couplers 62 to permit the injection of the water (fluid) within the internal portion of the conveyance component of the unit.\",\n \"An inventive industrial vacuum loader for positive displacement is shown in FIGS.\",\n \"28-31 with a tubular cylinder 71.Such a cylinder 71 is, as above, drilled for ports couplings 72 and are welded strategically to the outside cylinder wall.\",\n \"The orifice size of the port with or without nozzles can be varied as well as the angle of the port to increase or decrease the speed and efficiency of the vacuum accelerator 73.The air couplings are attached to the ports on the tubular cylinder 72.Flanges 74 are attached to the end of the tube 71 in various configurations, so that the vacuum accelerator can be attached to the vacuum or air conveyance columns.\",\n \"Air lines 75 are then attached to fittings, the air manifold 76 (4-way valve) to distribute air where needed and a separate airline for air inlet.\",\n \"The variable air valve 77 is then in place to control flow and pressure and is connected to the air supply 78.The pressure gauge 79 is then attached to monitor the overall unit.\",\n \"The nozzles 80 are then inserted within the couplers 72 to permit the injection of the gas (fluid) within the internal portion of the conveyance component of the unit.\",\n \"An inventive industrial street sweeper-type regenerative air style machine vacuum accelerator conveyance component is shown in FIGS.\",\n \"32-35 with a tubular cylinder 81.Such a cylinder 81 is, as above, drilled for ports couplings 82 and are welded strategically to the outside cylinder wall.\",\n \"The orifice size of the port with or without nozzles can be varied as well as the angle of the port to increase or decrease the speed and efficiency of the vacuum accelerator 83.The air couplings are attached to the ports on the tubular cylinder 82.Flanges 84 are attached to the end of the tube 81 in various configurations, so that the vacuum accelerator can be attached to the vacuum or air conveyance columns.\",\n \"Air lines 85 are then attached to fittings, the air manifold 86 (4-way valve) to distribute air where needed and a separate airline for air inlet.\",\n \"The variable air valve 87 is then in place to control flow and pressure and is connected to the air supply 88.The pressure gauge 89 is then attached to monitor the overall unit.\",\n \"The nozzles 90 are then inserted within the couplers 82 to permit the injection of the gas (fluid) within the internal portion of the conveyance component of the unit.\",\n \"An inventive long-distance water transport conveyance component having a 72 inch diameter tubular cylinder 91 is shown in FIGS.\",\n \"36-39.Such a cylinder 91 is, as above, drilled for ports couplings 92 and are welded strategically to the outside cylinder wall.\",\n \"The orifice size of the port with or without nozzles can be varied as well as the angle of the port to increase or decrease the speed and efficiency of the vacuum accelerator 93.The air couplings are attached to the ports on the tubular cylinder 92.Screw-type couplers (MPTH) 94 are attached to the end of the tube 91 in various configurations, so that the vacuum accelerator can be attached to the vacuum or air conveyance columns.\",\n \"Air lines 95 are then attached to fittings, the air manifold 96 (4-way valve) to distribute air where needed and a separate airline for air inlet.\",\n \"The variable air valve 97 is then in place to control flow and pressure and is connected to the air supply 98.The pressure gauge 99 is then attached to monitor the overall unit.\",\n \"The nozzles 100 are then inserted within the couplers 92 to permit the injection of the gas (fluid) within the internal portion of the conveyance component of the unit.\",\n \"An inventive particle accelerator (for a particle collider, for example) is shown in FIGS.\",\n \"40-43 with a miniature tubular cylinder 101 and a pulse electro-magnet 101A.\",\n \"Such a cylinder 101 is, as above, drilled for ports couplings 102 and are welded strategically to the outside cylinder wall.\",\n \"The orifice size of the port with or without nozzles can be varied as well as the angle of the port to increase or decrease the speed and efficiency of the vacuum accelerator 103.The air couplings are attached to the ports on the tubular cylinder 102.Flanges 104 are attached to the end of the tube 101 in various configurations, so that the vacuum accelerator can be attached to the vacuum or air conveyance columns.\",\n \"Air lines 105 are then attached to fittings, the air manifold 106 (4-way valve) to distribute air where needed and a separate airline for air inlet.\",\n \"The variable air valve 107 is then in place to control flow and pressure and is connected to the air supply 108.The pressure gauge 109 is then attached to monitor the overall unit.\",\n \"The nozzles 120 are then inserted within the couplers 102 to permit the injection of the gas (fluid) within the internal portion of the conveyance component of the unit.\",\n \"An inventive prosthetic heart valve (asymmetrical or symmetrical) vacuum accelerator conveyance component is shown in FIGS.\",\n \"44-47 with a very small tubular cylinder 111.Such a cylinder 111 is, as above, drilled for ports couplings 112 and are welded strategically to the outside cylinder wall.\",\n \"The orifice size of the port be varied as well as the angle of the port to increase or decrease the speed and efficiency of the vacuum accelerator 113.Blood is forced through the couplings 113 and nozzles 112 to effectuate the vortex effect within the tube 111.The air couplings 113 are attached to the ports 112 on the tubular cylinder 111.Suture ring flanges 114 are attached to the end of the tube 111 in various configurations, so that the vacuum accelerator can be attached to the vacuum or air conveyance columns in order to act in combination with a valve structure as needed.\",\n \"An inventive fuel injector with an added conveyance component is shown in FIGS.\",\n \"48-52 with a tubular cylinder 131.Such a cylinder 131 is, as above, drilled for ports couplings 132 and are welded strategically to the outside cylinder wall.\",\n \"The orifice size of the port with or without nozzles can be varied as well as the angle of the port to increase or decrease the speed and efficiency of the vacuum accelerator 133.The air couplings are attached to the ports on the tubular cylinder 131.Flanges 134 are attached to the end of the tube 131 in various configurations, so that the vacuum accelerator can be attached to the vacuum or air conveyance columns.\",\n \"Air lines 135 are then attached to fittings, the air manifold 136 (4-way valve) to distribute air where needed and a separate airline for air inlet.\",\n \"The variable air valve 137 is then in place to control flow and pressure and is connected to the air supply 138.The pressure gauge 139 is then attached to monitor the overall unit.\",\n \"The nozzles 140 are then inserted within the couplers 52 to permit the injection of the gas (fluid) within the internal portion of the conveyance component of the unit.\",\n \"The unit is introduced within a fuel injector 145, including a pressurized fuel line 154, fuel filter 155, an electrical boost attachment 153, a solenoid 152, a plunger 157, a valve spring 151, and a spray tip 150, all housed within a casing 156.When the fuel injector 145 is operated, the fuel pressure can be increased by the conveyance component as described above.\",\n \"Additionally, the source of the injector supply may be excess fuel that allows for recoupment and less waste thereof for extra economic benefits and efficiencies.\",\n \"In terms, then, of the actual operation of the invention, for all structures, basically, with a few notable exceptions, the tubular cylinder is to contain the material being conveyed or vacuumed.\",\n \"The ports with or without orifices are to convey air angularly against the inside sidewall of the cylinder to create negative pressure that creates a vortex effect inside the cylinder.\",\n \"Calibrate and attach air coupling to cylinder.\",\n \"The size, angle, and number of couplings depend on the vacuum acceleration required for the application.\",\n \"For example, a three-inch diameter tube vacuum accelerator might require fewer ports than a four-foot diameter vacuum accelerator.\",\n \"The angle of the port to the cylinder wall will affect the speed and negative pressure desired for the application.\",\n \"The flanges are installed to the tube so that it can attach to various vacuum columns inline.\",\n \"Air lines are attached to the fittings and run to air manifolds for air distribution where needed.\",\n \"A variable air valve is installed to regulate air flow and pressure and gauge is installed to regulate pressure.\",\n \"The unit will convey liquids and material even when not attached to vacuum column.\",\n \"The pressure gauge monitors the unit.\",\n \"The nozzles inserted into the couplers create directional pressure which increases velocity on the cylinder wall.\",\n \"The unit is also directional and configured to create vacuum acceleration when installed in the conveyance direction to direct material towards the vacuum in order to create negative pressure, and to create vacuum deceleration when installed in reverse.\",\n \"The overall components of the device may be of different materials themselves.\",\n \"In terms of, for instance, the tubular cylinder, such may be varied in size from just a few millimeters to 8-foot in diameter.\",\n \"As well, then, the tube may be constructed of a variety of materials such as; steel, abrasion-resistant steel, exten steel, corten steel, polyvinyl chloride, plastic resin, urethane, all forms of stainless steel, all forms of precious metals, copper, bronze, or even glass.\",\n \"The material chosen for the tube depends on the type of material one wants to convey.\",\n \"Flanges are next added to the cylinder-shaped tube.\",\n \"These flanges are normally constructed of the same material as the tube.\",\n \"Flanges can be band lock, flat flange, seamless, weld-able, or clamp together flanges of any nature.\",\n \"Basically, flange selection depends on the vacuum column to attachment is to be made.\",\n \"If the vacuum column uses flat flanges, then such should be utilized as well in conjunction with the cylinder.\",\n \"If the tube is made of metal, flanges may also be welded to the tubular cylinder.\",\n \"The flanges just serve the purpose of attaching the unit in-line to the vacuum column and or air conveyance column.\",\n \"Drilling, plasma cutting, torch utilization, etc., may be undertaken, as examples, to make appropriate holes in the tubular cylinder.\",\n \"The diameter of the holes, the size of the holes, and the number of holes depends on the speed of vacuum accelerator one desires.\",\n \"Couplings are then attached over the holes drilled in the tube.\",\n \"It is easier to attach the pressure nozzles into one end of the coupling and then attach the couplings to the tubular cylinder, generally, though not necessarily.\",\n \"If, for example, the tubular cylinder is metal, then the couplings can be welded, for example, at the correct angle with the nozzle facing the inside wall of the cylinder.\",\n \"If the tubular cylinder is PVC material, the same process may be followed, but the couplings are preferably cemented, for example, to the cylinder.\",\n \"The air couplings are then attached to the other end of the couplings that are welded to the tubular cylinder.\",\n \"The airlines are then attached to the air couplings and then to the air manifold.\",\n \"The variable air valve is attached to the manifold and a pressure gauge can then be added to monitor unit.\",\n \"The air supply is connected to the manifold inlet and all is ready to be utilized with the airlines intact within the nozzles.\",\n \"The size and type of material for the pressure nozzles can be varied to change the acceleration ratios.\",\n \"Some examples are ceramic nozzles versus carbide nozzles, or abrasion resistant steel nozzles depending on the material to be conveyed.\",\n \"The diameter and shape of the nozzle orifices can be altered to change the performance.\",\n \"The orifice size could be a couple of millimeters or less or several feet in diameter, depending on the size of vacuum accelerator needed.\",\n \"Nozzles may be made from a variety of materials and may be constructed from materials such as straight drilled pipe to very sophisticated tips with elongated holes, broad examples.\",\n \"The amount of air supplied to the unit can be varied from 1 cfm to hundreds of thousands of cfm.\",\n \"The size of the vacuum accelerator will depend on what vacuum or air conveyance column or structure one wants to attach the unit to.\",\n \"The type of air manifold can be varied depending on the application.\",\n \"Even the size, angle, material of ports can vary.\",\n \"To use this invention, one would attach the unit to the vacuum or air conveyance column, the liquid supply, or a blood supply, as needed; the supply is initiated and effectively begins the generation of the desired vortex effect, whether in terms of vacuum or air conveyance, whether positive or negative pressures (dependent on the direction of accelerator or decelerator in place).\",\n \"This invention could be used on street sweepers, environmental and industrial vacuum loaders, septic vacuum trucks and any vacuum or air conveyance system.\",\n \"This invention would increase productivity of these units at a lower cost.\",\n \"There are many industrial plant applications that need to convey material more efficiently at reduced costs.\",\n \"Industrial plants have miles of pipe that they utilize to move materials around their plants.\",\n \"Many of these plants use positive displacement blowers and or large air conveyance systems.\",\n \"The inventive vacuum accelerator can be attached to the pipe lines to reduce the frictional drag of the columns and to speed the conveyance of materials throughout the plant.\",\n \"This inventive device could also be utilized gas and oil pipelines to more efficiently convey materials longer distances at greater speed.\",\n \"Other variables that would help change dynamic pressure of the vacuum column are as follows: 1.The number of orifices and the location they are placed on a vacuum column.\",\n \"2.The size, shape and material the port orifices are made out of.\",\n \"3.If one were to add any type of lubricator to the system to reduce the frictional force.\",\n \"4.The diameter of the airlines, and the type of material they are made out of.\",\n \"Some examples are copper, steel, nylon, plastic and alloys.\",\n \"Thermo plastics and many heat resistant materials as well.\",\n \"5.The amount of air pressure supplied to the system.\",\n \"This is usually expressed in cfms.\",\n \"6.The actual air routing to the air supply, the manifold, and the size and type of manifold can all effect the change in dynamic pressure.\",\n \"7.Another variable that can be added to my invention to further increase the power of my vortex effect is the addition of a small electro-magnetic field to intensify the vortex effect.\",\n \"8.The shape of the tubular cylinder can be altered to effect dynamic pressure.\",\n \"For example, the shape of the tubular cylinder can be hexagonal rather than cylindrical or any irregular shape to affect the energy level from the vortex effect; this will in turn change the dynamic pressure of the vacuum column, and/or the air conveyance column velocity in turn.\",\n \"9.Another important note is that the vortex effect does not have to be perfectly symmetric to work.\",\n \"10.The invention device changes the densities and viscosity of substances in the vacuum column and/or air conveyance column.\",\n \"The energy created by the vortex will aid in the mixing of compounds being introduced to the human body.\",\n \"It will aid in the dynamic pressure and or air velocity necessary to create the appropriate mixture of compounds, liquids and or gases to achieve the desired result.\",\n \"Furthermore, in the bonding of substances on a molecular level, and or on an electron, proton and neutron basis, that energy, magnetism and pressure all affect the bonding of elements into compound substances.\",\n \"Thereby, the tremendous energy naturally found in a vortex, induced on to substances passed through my invention will aid medical science in the more efficient bonding and blending of substances and possibly the creation of new substances.\",\n \"As the vortex effect creates its own electro-magnetic field.\",\n \"This device can also change the temperature, thereby altering the characteristics and consistency of substances that passes through my invention.\",\n \"In other words, it will change the form of the matter that passes through the vortex effect.\",\n \"Depending on the direction the initial substance is passed through my invention, some substances will change molecularly due to the effects of magnetism on an elemental level.\",\n \"Substances will end up more negatively or positively charged even on a P orbital basis.\",\n \"In a science application, this device could also be used to aid research in electron and neutron acceleration, and potentially aid scientists in the creation of new substances and elements.\",\n \"F=ma Force=mass (acceleration) F=qE Therefore, this inventive device can help scientists change the acceleration or deceleration of electrons.\",\n \"The magnetic field created when an electron, proton or neutron, of an atom can be changed after passing through this vortex effect.\",\n \"Therefore, even a radioactive isotope could be altered from this vortex effect.\",\n \"In an electron application, this could be constructed on a smaller scale to a vacuum chamber and a free electron would be accelerated with a laser and a gas (most likely xenon) can be pressurized and sent through a heat resistant alloy gas manifold to the nozzle ports.\",\n \"Such that, the free electron passes through the tubular cylinder, with a laser (thermal energy) providing the dynamic pressure for the cylinder.\",\n \"Now as the electron passes through my invention it would gain velocity from a thermal vortex effect and would simulate fusion as an energy source.\",\n \"The electron would gain enormous speed as it passed through the thermal vortex effect cylinder.\",\n \"For this application the tubular cylinder would have to be made of a super heat resistant alloy and incorporate a low level electro-magnetic field to further impact the acceleration through the vortex effect.\",\n \"Pressurized air was utilized to create this vortex effect, however, any pressurized gas, liquid or solid could be substituted to create a change in the dynamic pressure of the vacuum column.\",\n \"For example, pressurized hydraulic fluid, food grade cooking oil, or even some of the product being transported could also be utilized to create a vortex effect on the vacuum column.\",\n \"Another example would be to use pressurized water in lieu of compressed air to create a vortex effect.\",\n \"The number of holes can be varied depending on the acceleration rate desired.\",\n \"Another variable is the size of the orifice or hole that will change the acceleration rate as well as the number of holes in the tube that pressurized air is being introduced to.\",\n \"In my model, I utilized ½ inch diameter holes with half inch airline and utilizes a variable air flow valve to control the flow of air and the orifice size and the deflection angle of the pressurized air hitting the inside sidewall of the cylinder and or tube controls the air and material speed of the accelerator and the inlet air pressure can all be adjusted to increase or decrease the speed of the materials through the pipe.\",\n \"Inlet air pressures and volumes of air can be adjusted to infinitely vary speed and achieve the desired reduction in friction and effective gravity on the material conveyed or being vacuumed i.e.\",\n \"Example negative pressure.\",\n \"The pressurized air when introduced to our cylinder creates a vortex effect inside the cylinder pipe that pulls material from one side of the cylinder and spins it out the opposite side with force.\",\n \"This effect works if the pipe is in a vertical, horizontal or any plane in between.\",\n \"When negative pressure is introduced to the push side of the vacuum accelerator something totally fascinating occurs.\",\n \"The frictional drag of material whether it is water, sludge, or aggregate or any mixture thereof in between on the cylinder is decreased and the effective weight of material in the material is decreased.\",\n \"Therefore, this translates into the material in the vacuum column to move at a faster rate with the vacuum system be it positive displacement blower or vein pump or any vacuum system drive.\",\n \"The vacuum accelerator accelerates the material speed and aids moving any type of material in a pipe or tubular application.\",\n \"The vacuum accelerator reduces the energy required to move material.\",\n \"The energy savings can be substantial.\",\n \"In a blower application the use of a vacuum accelerator can provide many benefits, for example: a vacuum accelerator can aid in moving material a longer distance than a blower system is currently capable of moving.\",\n \"In one test, we were able to convey material eight hundred feet through an eight-inch pipe by clamping two vacuum accelerators in line on a horizontal pull.\",\n \"Another great benefit of a vacuum accelerator is increasing the speed of loading material through a pipe.\",\n \"Still another benefit is the increase in negative pressure or vacuum with all other item constant which will translate in significant energy costs reductions and fuel savings for combustible fuel engines or electrical energy savings through reduced horsepower requirements.\",\n \"When a blower, vein or vacuum system is attached to a vacuum accelerator, the system shall require less energy to perform the same amount of work.\",\n \"Therefore, saving can also be realized by utilizing smaller engines and motors to preform vacuum work.\",\n \"Saving can be realized by the consumption of less fuel and energy by allowing the vacuum system to perform at less RPM revolutions per minute, saving component life on the systems as well.\",\n \"The Vacuum Accelerator, shall be a very cost-efficient unit.\",\n \"When a negative pressure vacuum system is applied to a vacuum accelerator the multiple reductions in energy is achieved by reducing the energy required on the vacuum system to preform work.\",\n \"Also, when a vacuum accelerator is applied to a centrifugal or centrifical compressor or any air conveyance system a vacuum accelerator works in the same accord, just at a different ratio.\",\n \"In an air conveyance system, a vacuum accelerator aids in the reduction of frictional drag and reducing the natural force of gravity on the material being conveyed.\",\n \"This in turn, reduces the amount of energy required to move material through any pipe or cylindrical application to convey material.\",\n \"In this case the vacuum accelerator is placed into line with the air conveyance column; the vacuum accelerator shall help the air conveyance system move material faster and with less energy than an air conveyance system without a vacuum accelerator.\",\n \"In this instance our unit actually becomes an air conveyance accelerator.\",\n \"The inverse is also true that if you turn the unit around and swap ends the unit becomes an air conveyance decelerator or a vacuum system decelerator by simply putting the opposite end of the pipe to the existing system.\",\n \"Therefore, this unit will also work to slow the material speed down if that is the effect desired.\",\n \"Another field-tested benefit of a vacuum accelerator is to reduce the time required to perform a vacuum job or to reduce the time to perform an air conveyance job of material or liquids.\",\n \"Typical applications shall be in vacuum of materials such as sewer, storm line and sludge debris and hazard materials vacuum systems that move aggregates and sludge.\",\n \"Street sweeper vacuum, air conveyance and regenerative air conveyance systems to reduce horsepower demands and fuel consumption, are examples.\",\n \"The Vacuum accelerators can be used to move more material at a faster rate into a debris body on a street sweeper or environmental conveyance vehicle.\",\n \"Another application is to use vacuum accelerators in industrial plants to move liquids and solids, in plant lines to reduce energy costs and to speed the vacuum column of material from one point to another are it in a horizontal, vertical plane or any combination in between.\",\n \"Another application is to use a vacuum accelerator in a lift station application to aid a lift station pump to move material in a force main and to move material into and from a treatment plant and or water or canal distribution plant.\",\n \"The power to move material into and from treatment plants is costly, many times employing high voltage (4160 volt) large motor driven electric generators that drive very large positive displacement blowers.\",\n \"A vacuum accelerator in line would decrease the energy required (start-up torque) and the energy required to maintain (running torque) of large blower systems.\",\n \"These units might be 36 inches to 72 inches in diameter depending on the system.\",\n \"The principle would be the same to reduce the amount of energy required to move liquids and aggregates through a column.\",\n \"Another application would be in fuel injection systems for automobiles.\",\n \"As we know electronic fuel injector systems electronically sense when to open and close to create base pulse width based on load and rpm.\",\n \"A vacuum accelerator would allow less fuel to be required for combustion as through the vortex effect a larger percentage of the liquid gas would be converted to a gaseous state, thereby decrease the pulse width required for an equivalent amount of combustion.\",\n \"Also, the velocity created would enhance combustion as well.\",\n \"These vacuum accelerators could be very small in size for example an eighth of an inch in diameter or smaller and installed in line into each injector system to decrease the amount of fuel required for combustion.\",\n \"A portion of the exhaust gas could be recycled and used as the air power source to create the vortex effect, there-by, reducing emissions while improving fuel economy simultaneously.\",\n \"In diesel engine applications a vacuum accelerator could be used in a direct injection system to move evenly circulate the diesel mist inside a cylinder to achieve improved combustion with a decreased amount of fuel.\",\n \"As the vortex effect would allow more efficient mixing and a larger percentage of gaseous diesels as opposed to liquid diesel thereby aiding combustion with decreased amounts of actual fuel.\",\n \"Exhaust air can be the supply force or a mixture of exhaust and intake air, by recycling the exhaust air stream two advantages are gained, the heated air stream aids combustibility and reduces emissions while aiding fuel efficiency.\",\n \"Another application relates to CNG gas transfer.\",\n \"One problem exists in the field of high pressure gas transfer.\",\n \"Currently, the methods are fast fill at around 3600 psi or up to 4300 psi and higher and slow fill at 3000 psi.\",\n \"Either method has its advantages and disadvantages in fill efficiency.\",\n \"Fast fill is approximately equal in the time required to liquid fill a tank and slow fill takes several hours, but fills the tanks to a greater volume.\",\n \"My invention shall reduce the time to fill the receiving tank in either situation.\",\n \"The other benefit is that the tanks shall fill with greater volume.\",\n \"The filling line is connected to one end of the vacuum accelerator via a high-pressure gas fitting.\",\n \"The opposite end is attached to the receiving tank.\",\n \"The supply hose for the vacuum accelerator is this case is attached to a lower pressure CNG fill tank.\",\n \"As the lower pressure gas enters the accelerator this causes a low-pressure area at the receiving tank inlet, increasing the differential pressure, which in turn causes the tank to fill more rapidly.\",\n \"An external cooler can be applied to the accelerator that actually lowers the temperature of the CNG gas and thus causes the receiving tank to fill to greater volume capacity as it decreases the expansion rate of the gas.\",\n \"The end result is that the receiving tanks are filled more efficiently.\",\n \"Another application relates to increasing propulsion efficiency by decreasing residual kinetic energy via a vacuum accelerator attached to air breathing jet engine.\",\n \"N(Overall energy efficiency)=Np(Propulsion Efficiency)×Nve(Cycle Efficiency) Therefore; for jet engines the propulsive efficiency is highest when the jet engine emits an exhaust jet at a velocity that is the same as, or nearly the same as, the vehicle speed as this gives the smallest residual kinetic energy.\",\n \"The formula for air breathing engines moving at speed v with an exhaust velocity Ve is given: Np ( Propulsion Efficiency ) = 2 1 + Ve / v The invention shall be attached to the end of the jet nozzle and the unit shall increase propulsion efficiency by lowering the residual kinetic energy.\",\n \"The vacuum decelerator shall slow the exhaust velocity thru its vortex effect when propulsion is required and the vacuum shall accelerate when the exhaust velocity needs to increase to reduce propulsion rapidly.\",\n \"The invention not only improves propulsion efficiency, it also is an excellent safety device that allows the pilot to vary his deceleration without causing stall.\",\n \"In addition, normal air fuel ratios of 50:1 rich to 130:1 weak limit vary depending on take-off, cruise and altitude, but because the invention reduces residual kinetic energy as exhaust velocity jet approaches velocity, significant fuel saving are achieved, and overall propulsion efficiency is optimized.\",\n \"My invention was also applied to an air conveyance system, and my invention changes the air velocity of an air conveyance column as well.\",\n \"In an electron application my invention would be constructed on a smaller scale to a vacuum chamber and a free electron would be accelerated with a laser and a gas most likely xenon can be pressurized and sent through a heat resistant alloy gas manifold to the nozzle ports, such that the free electron passes through the tubular cylinder, with a laser (thermal energy) providing the dynamic pressure for the cylinder.\",\n \"Now as the electron passes through my invention it would gain velocity from a thermal vortex effect and would simulate fusion as an energy source.\",\n \"Although specific applications and or embodiments of the invention have been described with reference to the drawing are by way of examples only and merely illustrate some of the many possible specific applications embodiments which represent application of the principles of the invention.\",\n \"Various changes, manipulations and/or obvious modifications to one skilled in the art to which the invention pertains are deemed to be within the scope, the spirit, essence, and contemplation of the invention as further defined within the following claims.\"\n ]\n]"},"source":{"kind":"string","value":"Patent_15871961"}}},{"rowIdx":4493966,"cells":{"text":{"kind":"list like","value":[["AUTOMATED MANUFACTURING SYSTEM WITH ADAPTER SECURITY MECHANISM AND METHOD OF MANUFACTURE THEREOF","A method of operation of an automated assembly system includes: detecting a socket adapter having an adapter identifier and an adapter cryptographic chip; calculating a primary key hash based on a primary key in a programming cryptographic chip; calculating an adapter hash based on the adapter identifier using the adapter cryptographic chip; matching the primary key hash to the adapter hash to update an authentication token with the adapter identifier for authenticating the socket adapter on the device programming system; and programming programmable devices in the socket adapter based on the authentication token."],["1.A method of operation of a security provisioning system comprising: calculating an adapter digital signature based on an adapter identifier using an adapter cryptographic chip on a socket adapter; calculating a programmer digital signature based on the adapter identifier using a programming cryptographic chip of a device programming system; authenticating the socket adapter by matching the adapter digital signature to the programmer digital signature; and programming programmable devices in the socket adapter upon authentication of the of the socket adapter.","2.The method as claimed in claim 1 wherein calculating the adapter digital signature includes calculating the adapter digital signature based on the adapter identifier and a primary key.","3.The method as claimed in claim 1 wherein the calculating the programmer digital signature includes calculating the programmer digital signature using a primary key and the adapter identifier retrieved from the socket adapter.","4.The method as claimed in claim 1 wherein authenticating the socket adapter includes comparing an adapter hash generated by the adapter cryptographic chip to a primary key hash generated by the programming cryptographic chip.","5.The method as claimed in claim 1 further comprising preventing the programming of the programmable devices upon the failure of the authentication of the socket adapter.","6.A method of operation of a security provisioning system comprising: encoding a primary key inside an adapter cryptographic chip and a programming cryptographic chip; calculating an adapter digital signature based on an adapter identifier and the primary key using the adapter cryptographic chip on a socket adapter; calculating a programmer digital signature based on the adapter identifier and the primary key using the programming cryptographic chip of a device programming system; authenticating the socket adapter by matching the adapter digital signature to the programmer digital signature; and programming programmable devices in the socket adapter upon authentication of the of the socket adapter.","7.The method as claimed in claim 6 wherein calculating the adapter digital signature includes calculating the adapter digital signature using an advanced encryption standard method, an elliptical curve method, or a combination thereof.","8.The method as claimed in claim 6 wherein programming the programmable devices includes programming the programmable devices in a destination socket of the socket adapter.","9.The method as claimed in claim 6 wherein encoding the primary key includes receiving the primary key from a security key instantiation controller over a secure network.","10.The method as claimed in claim 6 wherein encoding the primary key includes transferring the primary key from a security key instantiation controller to the programming cryptographic chip.","11.A security provisioning system comprising: a socket adapter having an adapter identifier; an adapter cryptographic chip on the socket adapter, for calculating an adapter digital signature based on the adapter identifier; a programming cryptographic chip in a device programming system, coupled to the socket adapter, for calculating a programmer digital signature based on the adapter identifier; and a programming processor, coupled to the device programming system, for authenticating the socket adapter by matching the adapter digital signature to the programmer digital signature and programming programmable devices in the socket adapter upon authentication of the socket adapter.","12.The system as claimed in claim 11 wherein the adapter digital signature is based on the adapter identifier and the primary key.","13.The system as claimed in claim 11 wherein the programmer digital signature is calculated using a primary key and the adapter identifier retrieved from the socket adapter.","14.The system as claimed in claim 11 wherein the adapter cryptographic chip is for comparing an adapter hash generated by the adapter cryptographic chip to a primary key hash generated by the programming cryptographic chip.","15.The system as claimed in claim 11 wherein the programming processor is for preventing the programming of the programmable devices upon the failure of the authentication of the socket adapter.","16.The system as claimed in claim 11 wherein the primary key is encoded inside the adapter cryptographic chip and the programming cryptographic chip.","17.The system as claimed in claim 16 wherein the adapter digital signature is calculated using an advanced encryption standard system, an elliptical curve system, or a combination thereof.","18.The system as claimed in claim 16 wherein the socket adapter includes a destination socket for programming the programmable devices.","19.The system as claimed in claim 16 further comprising a secure network for transferring the primary key from a security key instantiation controller to the device programming system.","20.The system as claimed in claim 16 further comprising a security key instantiation controller transferring the primary key to the programming cryptographic chip."],[" BACKGROUND ART Most of the world's electronic manufacturers do not possess the ability to build highly proficient multi-module automated processing systems, such as a manufacturing system that contain fully integrated robotics systems.","There is a desire to standardize manufacturing processes across multiple manufacturing sites world-wide.","In order to reduce development costs some manufacturers have reverse engineered manufacturing devices.","The risks of exposure or proprietary manufacturing processes and client intellectual property can restrict product manufacturing to dedicated sites utilizing certified assembly devices.","This can restrict the available volumes of products without regard to potential increased demand and dwindling supplies.","Some manufacturing capacity can be underutilized because the required processes and intellectual property cannot be transferred to additional sites.","The exposure or loss of the manufacturing process or the client intellectual property is too great for unsecured movement between manufacturing facilities.","Compromise of the manufacturing process or the client's intellectual property can represent a business calamity that could ruin the manufacturer's reputation and risk future business opportunity.","Thus, a need still remains for an automated manufacturing system with adapter security that can effectively protect the manufacturing process and the client's intellectual property, while being able to distribute the workload across multiple sites as required to meet the client's manufacturing needs.","In view of the ever-increasing need to save costs and improve efficiencies, it is more and more critical that answers be found to these problems.","Solutions to these problems have been long sought but prior developments have not taught or suggested any solutions and, thus, solutions to these problems have long eluded those skilled in the art."],[" BRIEF DESCRIPTION OF THE DRAWINGS FIG.","1 is a functional block diagram of an automated assembly system in accordance with an embodiment of the present invention; FIG.","2 is an isometric view of a device programming system; FIG.","3 is an isometric view of one of the socket adapters; FIG.","4 is a functional block diagram of an adapter security system; FIG.","5 is an exemplary process flow of the operation of the adapter security system; FIG.","6 is a functional block diagram of a security provisioning system; FIG.","7 is an exemplary process flow of the operation of the security provisioning system; and FIG.","8 is a flow chart of an automated manufacturing system for operating the automated manufacturing system in accordance with an alternative embodiment of the present invention.","detailed-description description=\"Detailed Description\" end=\"lead\"?"],["CROSS-REFERENCE TO RELATED APPLICATION(S) This application claims benefit as a Continuation of U.S. application Ser.","No.","14/921,833, filed Oct. 23, 2015, which claims the benefit of U.S.","Provisional Patent Application Ser.","No.","62/098,257 filed Dec. 30, 2014, the entire contents of the aforementioned are hereby incorporated by reference as if fully set forth herein, under 35 U.S.C.","§ 120.The applicant(s) hereby rescind any disclaimer of claim scope in the parent application(s) or the prosecution history thereof and advise the USPTO that the claims in this application may be broader than any claim in the parent application(s).","TECHNICAL FIELD The present invention relates generally to automated systems, and more particularly to automated manufacturing systems with adapter security mechanism for manufacturing operations.","BACKGROUND ART Most of the world's electronic manufacturers do not possess the ability to build highly proficient multi-module automated processing systems, such as a manufacturing system that contain fully integrated robotics systems.","There is a desire to standardize manufacturing processes across multiple manufacturing sites world-wide.","In order to reduce development costs some manufacturers have reverse engineered manufacturing devices.","The risks of exposure or proprietary manufacturing processes and client intellectual property can restrict product manufacturing to dedicated sites utilizing certified assembly devices.","This can restrict the available volumes of products without regard to potential increased demand and dwindling supplies.","Some manufacturing capacity can be underutilized because the required processes and intellectual property cannot be transferred to additional sites.","The exposure or loss of the manufacturing process or the client intellectual property is too great for unsecured movement between manufacturing facilities.","Compromise of the manufacturing process or the client's intellectual property can represent a business calamity that could ruin the manufacturer's reputation and risk future business opportunity.","Thus, a need still remains for an automated manufacturing system with adapter security that can effectively protect the manufacturing process and the client's intellectual property, while being able to distribute the workload across multiple sites as required to meet the client's manufacturing needs.","In view of the ever-increasing need to save costs and improve efficiencies, it is more and more critical that answers be found to these problems.","Solutions to these problems have been long sought but prior developments have not taught or suggested any solutions and, thus, solutions to these problems have long eluded those skilled in the art.","DISCLOSURE OF THE INVENTION The embodiments of the present invention provides a method of operation of an automated assembly system including: detecting a socket adapter having an adapter identifier and an adapter cryptographic chip; calculating a primary key hash based on a primary key in a programming cryptographic chip; calculating an adapter hash based on the adapter identifier using the adapter cryptographic chip; matching the primary key hash to the adapter hash to update an authentication token with the adapter identifier for authenticating the socket adapter on the device programming system; and programming programmable devices in the socket adapter based on the authentication token.","The embodiments of the present invention provides an automated manufacturing system, which includes: a socket adapter having an adapter identifier; a programming cryptographic chip, coupled to the socket adapter, for calculating a primary key hash based on a primary key; an adapter cryptographic chip, coupled to the socket adapter, for calculating an adapter hash based on the adapter identifier; and a programming processor, coupled to the programming cryptographic chip, for matching the primary key hash to the adapter hash to update an authentication token with the adapter identifier for authenticating the socket adapter to enable programming programmable devices in the socket adapter based on the authentication token.","Certain embodiments of the invention have other steps or elements in addition to or in place of those mentioned above.","The steps or element will become apparent to those skilled in the art from a reading of the following detailed description when taken with reference to the accompanying drawings.","BRIEF DESCRIPTION OF THE DRAWINGS FIG.","1 is a functional block diagram of an automated assembly system in accordance with an embodiment of the present invention; FIG.","2 is an isometric view of a device programming system; FIG.","3 is an isometric view of one of the socket adapters; FIG.","4 is a functional block diagram of an adapter security system; FIG.","5 is an exemplary process flow of the operation of the adapter security system; FIG.","6 is a functional block diagram of a security provisioning system; FIG.","7 is an exemplary process flow of the operation of the security provisioning system; and FIG.","8 is a flow chart of an automated manufacturing system for operating the automated manufacturing system in accordance with an alternative embodiment of the present invention.","BEST MODE FOR CARRYING OUT THE INVENTION The following embodiments are described in sufficient detail to enable those skilled in the art to make and use the invention, and it is to be understood that other embodiments would be evident based on the present disclosure and that process or mechanical changes may be made without departing from the scope of the present invention.","In the following description, numerous specific details are given to provide a thorough understanding of the invention.","However, it will be apparent that the invention may be practiced without these specific details.","In order to avoid obscuring the present invention, some well-known system configurations, and process steps are not disclosed in detail.","Likewise, the drawings showing embodiments of the invention are semi-diagrammatic and not to scale and, particularly, some of the dimensions are for the clarity of presentation and are shown exaggerated in the drawing FIG's.","In addition, where multiple embodiments are disclosed and described having some features in common, for clarity and ease of illustration, description, and comprehension thereof, similar and like features one to another will ordinarily be described with like reference numerals.","The term “horizontal” as used herein is defined as a plane parallel to the plane or surface of the operating plane of an automated assembly system, regardless of its orientation.","The term “vertical” refers to a direction perpendicular to the horizontal as just defined.","Terms, such as “on”, “above”, “below”, “bottom”, “top”, “side” (as in “sidewall”), “higher”, “lower”, “upper”, “over”, and “under”, are defined with respect to the horizontal plane.","Referring now to FIG.","1, therein is shown a functional block diagram of an automated assembly system 100 in accordance with an embodiment of the present invention.","The automated assembly system 100 is a mechanism for configuring programmable devices.","The automated assembly system 100 can include a system controller 110 and one or more assembly devices 108.The automated assembly system 100 can be configured to accept modules with an intelligent design.","These intelligently designed modules are configured to interface with the automated assembly system 100.The automated assembly system 100, can be an automated programming system, can immediately recognizes module information such as the identification of the module, the type of module, the configuration of the module, the geometry of the module, and the location of the module within the system or feeder bank.","For example, configuration information about the assembly devices that, can be programming modules, provide socket count, socket pitch, socket offset, socket location, and the number of programming sites.","On the other hand, an intelligently designed tape module may simply provide information about the pocket offset.","The automated assembly system 100 can include a backplane 112, a first intelligent module 114, a second intelligent module 116, an Nth intelligent module 118, and the system controller 110.The backplane provides a data, control, and power, communication interface for the smart interface system.","For example, the backplane may provide a transmission interface for the first intelligent module, the second intelligent module, and the Nth intelligent module, wherein the Nth intelligent module represents any module number greater than one.","It is understood that the automated assembly system 100 can include any number of the intelligent modules and each of the intelligent modules can control the assembly devices 108.Each of the modules contains a data port 122, a control port 124, and a power port 126.The control port 124 can be used to transmit commands to and status between the modules.","For example, track identification information, such as the physical location of each module, can be transferred through the control port 124.The data port 122 can be used to broadcast device image data, send commands, and receive status information for programming operations.","Due to the volume of data transmitted by the data port 122, a high-speed port, such as an Ethernet connection is usually employed.","Any module that would require the transmission of large amounts of data could use the data port 122.The power port 126 transmits power to each module through the backplane.","The power supplied to each module via the power port 126 can be electrical, but in principle, it could be mechanical, pneumatic, hydraulic, magnetic, optical, chemical, or a combination thereof.","The data port 122, the control port 124, and the power port 126 are collectively referred to as a composite connection 128.As the composite connection 128 may protrude from the module, a mechanical protection scheme can be designed to protect it from accidental damage.","The composite connection 128 may also employ a hardware based naming format.","This format will allow configurable hardware switches on each module that not only differentiate by the type of module, but also by a module serial number of each module.","The composite connection 128, when coupled to the smart interface system, may employ a mechanical fit connection that consists of pins and spring-loaded washers.","Each module may use an identical set pitch for the composite connection 128 pins.","This type of configuration provides for uniform mounting and consistent registration for each of the composite connection 128.Additionally, the pin and spring loaded washer type of connection establishes a reliable and repeatable tool-less installation that requires minimal time.","Each module can be installed by merely establishing preliminary contact and then registering or locking in place.","The data port 122, the control port 124 and the power port 126 of each one of the modules is coupled with a central control 130, a robot control 132, and a local power 134, respectively, within the system controller 110.The system controller 110 acts as a processing component for receiving and transmitting information between the non-text user interface system and each of the modules.","Each of the control port 124 includes a track information system for communicating track identification information with the backplane.","The track identification information may include a unique identification number and a unique location designation.","For example, the first intelligent module, the second intelligent module, and the Nth intelligent module each possess the ability to transmit track information.","A software protocol 136 that delivers information through the data port 122 and the control port 124 is a bi-directional protocol.","For example, the data port 122 can use an Ethernet port and the control port 124 can use a Controller Area Network (CAN) port with a hard coded segment for carrying track identification information.","This bi-directional protocol allows for data and controls (digital and analog) communication.","Each module may use this common protocol to enhance interchangeability within the system.","The software protocol 136 can also employ a multiple master system, which allows any component within the automated manufacturing system to request or send data.","For example, the input module could request data from one of the programming modules without any need for the robot control 132 within the system controller 110 to initiate a transverse request.","The software protocol 136 also includes a messaging system 138, which can relay information between components.","For example, the messaging system 138 can relay information about whether or not the adapters are open or closed, and what type of modules are installed within the system.","The messaging system 138 may include a prioritized messaging system, wherein both of these systems are based on the Controller Area Network (CAN) protocol.","The present invention employs a unique set of CAN messages.","All messages within the CAN system are based on a message number, with lower numbered messages receiving the higher priority.","So, if two messages are sent simultaneously, the message with the lowest value will get through, and the other message will have to wait to be retransmitted at a later date.","Any cryptographic solution involves a secret key, such as a primary key or a root key.","The biggest issue with keys is how to keep them as a secret.","Usually software embeds the key in some obscure needle in the hay stack model.","Using today's supercomputers, these are easily breakable.","The current system insures no one ever knows the primary key.","It is never kept in any software.","No one really knows the key, not even the developers who coded the software.","The key is kept in hardware and could never be read out.","It can only be used internally to an integrated circuit for cryptographic operations.","Referring now to FIG.","2, therein is shown an isometric view of a device programming system 201.The device programming system 201 can include a programming processor 218, an input device receptacle 204, socket adapters 206, destination sockets 208, a device placement unit 210, programmable devices 212, and an output device receptacle 214.The device programming system 201 can be the automated assembly system 100 of FIG.","1.The automated assembly system 100 is a mechanism for configuring programmable devices 212.The automated assembly system 100 can configure the programmable devices 212 by initializing and writing a data image into the programmable devices 212.The programmable devices 212 can include Flash memory devices, programmable read-only memory, hybrid devices having processing and memory elements, or a combination thereof.","The automated assembly system 100 can include the system controller 110 of FIG.","1 and one or more of the assembly devices 108 of FIG.","1.Each of the assembly devices 108 can configure and program one or more of the programmable devices 212.The device programming system 201 is a device for configuring the programmable devices 212.The device programming system 201 can load an entire chip image at a time and then configure the programmable devices 212.Configuring is defined as writing control and data information to the programmable devices 212.Configuring the programmable devices 212 can store memory structure, cryptographic data, and user data on the programmable devices 212.Configuring can include forming one-time structures such as partitions on the programmable devices 212.The device programming system 201 can include the programming processor 218.The programming processor 218 is a computing unit for controlling the device programming system 201.The programming processor 218 can include a central processing unit (not shown), a local storage unit 203, a communication interface (not shown), and a software (not shown).","The programming processor 218 can have a variety of configurations.","For example, the programming processor 218 can include the system controller 110 or be coupled to the system controller 110.The programming processor 218 can be a single processor, a multiprocessor, a cloud computing element, or a combination thereof.","The local storage unit 203 is a device for storing and retrieving information.","For example, the local storage unit 203 of the device programming system 201 can be a disk drive, a solid-state memory, an optical storage device, or a combination thereof.","The software is control information for executing on the control unit.","The software can be used to control the functionality of the device programming system 201.The device programming system 201 can include the input device receptacle 204 and the output device receptacle 214.The input device receptacle 204 is a source of the programmable devices 212.For example, the input device receptacle 204 can be a tray that conforms to the Joint Electron Device Engineering Council (JEDEC) standards.","The input device receptacle 204 can be used for holding unprogrammed devices.","The output device receptacle 214 is a destination for the programmable devices 212 that have been processed.","For example, the output device receptacle 214 can be an empty JEDEC tray for holding finished devices.","The device programming system 201 can include the socket adapters 206 having the destination sockets 208.The socket adapters 206 are mechanisms for holding and managing sockets.","The sockets are mechanisms for holding and interfacing with the programmable devices 212.The socket adapters 206 are modular and can be removed from the device programming system 201 to accommodate different socket configurations.","For example, the socket adapters 206 can include a latch mechanism (not shown) for attaching to the device programming system 201.The socket adapters 206 are secure devices that can authenticate themselves with the device programming system 201 using a cryptographic challenge process to allow access to the socket adapters 206.The socket adapters 206 are described in greater detail below.","The destination sockets 208 can hold the programmable devices 212.In general, the destination sockets 208 can be used to read or write new information to one of the programmable devices 212.The device programming system 201 can include the device placement unit 210.The device placement unit 210 is a mechanism for positioning a programmable device in one of the destination sockets 208.The device placement unit 210 can be implemented in a variety of ways.","For example, the device placement unit 210 can be a robotic arm, a pick and place mechanism, or a combination thereof.","Although the device placement unit 210 is described as a rail-based positioning system, it is understood that any system capable of positioning one of the programmable devices 212 in the destination sockets 208 can be used.","The device placement unit 210 can retrieve one or more of the programmable devices 212 that are blank from the input device receptacle 204.The device placement unit 210 can transport the programmable devices 212 to the destination sockets 208 of the socket adapters 206.Once the programmable devices 212 are engaged and secured by the socket adapters 206, the device programming process can begin.","The device programming system 201 can program a local copy of the information into the programmable devices 212 in one of the destination sockets 208.For example, the local copy of the programming information can be in a pre-programmed master device, from a file in local storage, or from a remote server.","Once programming is complete, the device placement unit 210 can transport the programmable devices 212 that have been programmed to the output device receptacle 214.The device placement unit 210 can transports any of the programmable devices 212 that have errors to a reject bin (not shown).","The automated assembly system 100 can include an automatic receptacle mapping feature 216.The automatic receptacle mapping feature 216 will automatically measure the physical characteristics and connector geometry of the programmable devices, such as the number of rows and columns, the row offset and pitch, and the column offset and pitch.","These automatic measurements provide information about the exact coordinates, for example X, Y, Z, and theta directions or sometimes only X and Y directions for each center of pocket within each receptacle.","This can include the location for each device.","The automatic receptacle mapping feature 216 employs optical methods based upon, changes of state, such as reflectivity, and specifically designed algorithms to calculate receptacle location, geometry and physical characteristics.","This mapping feature is designed in such a way that the operator no longer has to manually enter in the physical characteristics and geometry of the programmable device and the destination sockets 208, which saves the operator time and prevents operator input error.","The automated assembly system 100 can include a programming system identifier 220.The programming system identifier 220 is a unique value for each particular one the device programming system 201.The programming system identifier 220 can be used to uniquely identify each one of the device programming system 201.Referring now to FIG.","3, therein is shown an isometric view of one of the socket adapters 206.The socket adapters 206 can include an adapter cryptographic chip 302, an adapter base 304, and one or more of the destination sockets 208 for retaining the programmable devices 212 of FIG.","2.Each of the socket adapters 206 can include an adapter identifier 306.The adapter identifier 306 is a unique number associated with each one of the socket adapters 206.For example, the adapter identifier 306 can be a serial number, a part number, a random number, a calculated cryptographic key, or a combination thereof.","The adapter cryptographic chip 302 is an electronic component for performing crypto-authentication.","The adapter cryptographic chip 302 can respond to a cryptographic challenge 328 by calculating a response key 326.The response key 326 can be based on the adapter identifier 306 of one of the socket adapters 206.The cryptographic challenge 328 is described in greater detail below.","For example, the adapter cryptographic chip 302 can be from the Atmel family of crypto-authentication chips including the ATAES132A, the ATECC108A, the ATSHA204A, or the ATECC508A.","The adapter cryptographic chip 302 can implement a variety of security models including the Advanced Encryption Standard (AES), Elliptical curve cryptography (ECC), Elliptic Curve Diffie-Hellman (ECDH), or a combination thereof.","The socket adapters 206 can have a variety of configuration.","For example, the socket adapters 206 can include four of the destination sockets 208 for configuring the programmable devices 212.Although the socket adapters 206 are shown with four sockets, it is understood that the socket adapters 206 any number and combination of the destination sockets 208.The destination sockets 208 can be used for reading and writing the programmable devices 212.The destination sockets 208 can be used to read from a pre-programmed device.","The destination sockets 208 are only used to configure the programmable devices 212 that are blank or unprogrammed.","The destination sockets 208 of the socket adapters 206 can be coupled to the device programming system 201 of FIG.","2 with contacts (not shown) on the top and bottom of the socket adapters 206.The device programming system 201 can access to the adapter cryptographic chip 302 via the contacts for authentication of the socket adapters 206.Referring now to FIG.","4, therein is shown a functional block diagram of an adapter security system 402.The functional block diagram depicts an operator console 401 having an authentication manager software 404 coupled to the automated assembly system 100 of FIG.","1 over a secure network 403.The automated assembly system 100 of FIG.","1 can include the device programming system 201 of having one or more of the socket adapters 206.The automated assembly system 100 can include the device programming system 201 having one or more of the socket adapters 206.The device programming system 201 can include a programming processor 218 running a programming firmware 410.The programming processor 218 is coupled to a cryptographic chip, such as a programming cryptographic chip 412.For example, the cryptographic chip can be from the Atmel family of crypto-authentication chips including the ATAES132A, the ATECC108A, the ATSHA204A, or the ATECC508A.","The cryptographic chip can implement a variety of security models including the Advanced Encryption Standard (AES), Elliptical curve cryptography (ECC), Elliptic Curve Diffie-Hellman (ECDH), or a combination thereof.","The programming cryptographic chip 412 can include an internal copy of a primary key 414.The primary key 414 can be a master trusted root key or other unique cryptographic key.","The primary key 414 is a unique value associated with the automated assembly system 100 that can be used to validate the trust relationship between entities.","The primary key 414 is described in greater detail below.","The programming cryptographic chip 412 can be provisioned and assigned the primary key 414 in an initialization process.","Once the programming cryptographic chip 412 has been configured with the primary key 414, the primary key 414 is stored in an area of internal memory that cannot be accessed from outside the programming cryptographic chip 412.The primary key 414 is a unique identifier to identify the individual automated assembly system 100.Each one of the individual automated assembly system 100 can have a unique value for the primary key 414.The automated assembly system 100 can be deployed in a facility controlled by a client.","The automated assembly system 100 can be used to configure programmable devices installed in the socket adapters 206.However, the automated assembly system 100 will authenticate each of the socket adapters 206 by indirectly comparing the value of the primary key 414 with the value of the adapter identifier 306.The automated assembly system 100 can authenticate the socket adapters 206 using an assembly level challenge 418.In the assembly level challenge 418, the adapter security system 402 can authenticate each of the socket adapters 206 by comparing a primary key hash 320 with an adapter hash 321.The programming cryptographic chip 412 can calculate the primary key hash 320 and the adapter cryptographic chip 302 of FIG.","3 can calculate the adapter hash 321.The two hash values are compared and one of the socket adapters 206 is authenticated if the two hash values match.","The primary key hash 320 is a calculated value based on the primary key 414 and the adapter identifier 306 of the socket adapters 206.The primary key 414 remains securely stored internally within the programming cryptographic chip 412 and cannot be directly accessed from outside any of the programming cryptographic chip 412.The primary key hash 320 can be calculated by the programming cryptographic chip 412 by submitting the adapter identifier 306 of one of the socket adapters 206 to the programming cryptographic chip 412.The primary key hash 320 is internally calculated by the programming cryptographic chip 412 and is based on the primary key 414 and the adapter identifier 306.The adapter identifier 306 can be retrieved from the socket adapters 206.The adapter security system 402 can calculate the adapter hash 321 by interrogating the adapter cryptographic chip 302 of one of the socket adapters 206.Each of the socket adapters 206 can include an internal copy of the primary key 414 stored within the adapter cryptographic chip 302.The programming firmware 410 can send a command or the cryptographic challenge 328 of FIG.","3 to the socket adapters 206 instructing the adapter cryptographic chip 302 to calculate the adapter hash 321.The adapter hash 321 is based on the internally stored copy of the primary key 414 in the adapter cryptographic chip 302 and the adapter identifier 306.The programming processor 218 running the programming firmware 410 can compare the primary key hash 320 and the adapter hash 321 and if the values match, then the selected one of the socket adapters 206 is authenticated.","When one of the socket adapters 206 has been authenticated, then the adapter security system 402 can enable one of the socket adapters 206 for operation.","If one of the socket adapters 206 is unauthenticated, then the adapter security system 402 can prevent the use of the one of the socket adapters 206 that has failed authentication.","The programming processor 218 can execute the programming firmware 410 to request the calculation of the primary key hash 320 by the programming cryptographic chip 412 and request the calculation of the adapter hash 321 based on the adapter identifier 306.The programming processor 218 can then compare the primary key 414 and the adapter hash 321 to authenticate the socket adapters 206.If the hashes match, then the automated assembly system 100 can program the programmable devices 212 of FIG.","2 coupled to the socket adapters 206.By only comparing the primary key hash 320 and the adapter hash 321, the primary key 414 can remained hidden and is not exposed outside the cryptographic chips.","Authentication of the socket adapter 206 allows the socket adapter 206 to be used by the device programming system 201.For example, matching the primary key hash 320 to the adapter hash 321 can set an authentication token 420 to the value of the adapter identifier 306 to indicate that the selected one of the socket adapters 206 is authenticated.","The authentication token 420 can be a single value, a list, a matrix, a hybrid data structure, or a combination thereof.","In an illustrative example, the device programming system 201 can detect the socket adapter 206 that is unauthorized if the adapter identifier 306 is not referenced in the authentication token 420.If the one of the socket adapters 206 is unauthorized, then the device programming system 201 can prevent access to the indicated one of the socket adapters 206.It has been discovered that authenticating one of the socket adapters 206 by calculating the primary key hash 320 and the adapter hash 321 increases security by insuring that the socket adapters 206 are authorized to operate within the device programming system 201.By verifying that the same value of the primary key 414 is in each of the cryptographic chips, secure operation can be provided.","Referring now to FIG.","5, therein is shown an exemplary process flow of the operation of the adapter security system 402 of FIG.","4.The adapter security system 402 can authenticate the socket adapters 206 of FIG.","2 by comparing the primary key hash 320 of FIG.","3 and the adapter hash 321 of FIG.","3 for each of the socket adapters 206.In an illustrative example, the operator console 401 of FIG.","4 can send a request to the automated assembly system 100 of FIG.","1 to authenticate the socket adapters 206.An authentication process for the socket adapters 206 at customer manufacturing site can be as follows: In an adapter request step 502, the authentication manager software 404 of FIG.","4 in the operator console 401 can request the programming firmware 410 of FIG.","4 in the programming processor 218 to authenticate one of the socket adapters 206 that has been newly inserted.","In a programming authentication step 504, the programming firmware 410 requests the programming cryptographic chip 412 of FIG.","4 on the system controller 110 of FIG.","1 to authenticate the socket adapters 206 with the cryptographic challenge 328 of FIG.","3.In an authentication sequence step 506, the programming cryptographic chip 412, which has the primary key 414 of FIG.","4 internally, starts the cryptographic challenge 328.The cryptographic challenge 328 is an answer and response protocol used for authentication.","For example, the actions of the authentication sequence step 506 can be as follows: 1.The device programming system 201 of FIG.","2 can interrogate the socket adapters 206 to get the adapter identifier 306 of FIG.","3 from one of the socket adapters 206.2.The programming processor 218 of FIG.","2 and the programming cryptographic chip 412 can generate the assembly level challenge 418 of FIG.","4 and send it to the socket adapters 206.3.Each of the socket adapters 206 combines the adapter identifier 306, the internal copy of the primary key 414 on-board the adapter cryptographic chip 302 of FIG.","3, and the assembly level challenge 418 received and computes the adapter hash 321.4.The socket adapters 206 return the challenge response 322 of FIG.","3 to the programming cryptographic chip 412 in the system controller 110.The challenge response 322 includes the adapter hash 321.5.The programming processor 218 and the programming cryptographic chip 412 extract the adapter identifier 306 by comparing the primary key hash 320 to the adapter hash 321.The adapter identifier 306 will only be correct if it was properly encoded and decoded using the same value of the primary key 414.For example, if the adapter identifier 306 decoded from the adapter hash 321 using the primary key 414 matches, then this one of the socket adapters 206 will be authenticated.","In a matching step 508, the primary key hash 320 will only match the adapter hash 321 only if the primary key 414 on the device programming system 201 of FIG.","2 and the unknown key of the socket adapters 206 match.","The matching step 508 can be performed in a variety of ways.","For example, the programming processor 218 and the programming cryptographic chip 412 can compare the primary key hash 320 and the adapter hash 321 for authentication.","In another example, the programming processor 218 and the programming cryptographic chip 412 can extract and compare the adapter identifier 321 from each of the hashes.","In yet another example, the device programming system 201 can extract and compare other security values encoded within both the primary key hash 320 and the adapter hash 321.The programming cryptographic chip 412 has special properties not to reveal the key, but use it only internally in the calculation of the primary key hash 320.For example, if the primary key hash 320 and the adapter hash 321 match, then the authentication token 420 of FIG.","4 is updated with the adapter identifier 306 It has been discovered that the above communication process increases security by inhibiting code breaking processes by not exposing the primary key 414.The primary key 414 never gets exposed outside of the cryptographic chip, so monitoring the bus does not allow anyone to detect the primary key 414.It has been discovered that the above communication process prevents code breaking processes by calculating the primary key hash 320 while not exposing the primary key 414.The primary key 414 remains hidden in the programming processor 218 or the socket adapters 206, so the primary key 414 cannot be detected by hardware monitoring.","It has been discovered that configuring the socket adapters 206 with the adapter cryptographic chip 302 can increase security by preventing the programming of the programmable devices 212 of FIG.","2 that are not coupled to one of the socket adapters 206 that has been authenticated.","Restricting the transfer of sensitive content or code to the programming devices 212 to only those mounted on authenticated ones of the socket adapters 206 reduces piracy and is an effective element of a comprehensive security system for programming programmable devices 212.It has been discovered that configuring the socket adapters 206 with the adapter cryptographic chip 302 can increase process integrity by allowing the tracking of the socket adapters 206 using the adapter identifier 306.Logging the adapter identifier 306 as part of the manufacturing process provides a secure audit trail to document this portion of the manufacturing process down to the adapter and device level.","Referring now to FIG.","6, therein is shown a functional block diagram of a security provisioning system 602.The security provisioning system 602 includes a security key instantiation controller 610 coupled to the device programming system 201.The security key instantiation controller 610 can include a control processor 612, the operator console 401, a manufacturing security database 616, a reference controller 618, a secure bootstrap firmware 604, and an initializing cryptographic chip 614.The device programming system 201 can include the programming processor 218, the programming cryptographic chip 412, the programming system identifier 220, and one or more of the socket adapters 206.Each of the socket adapters 206 includes the adapter cryptographic chip 302.Each of the socket adapters 206 can include the adapter identifier 306.The security provisioning system 602 can provision the adapter cryptographic chip 302 and the programming cryptographic chip 412 with the primary key 414 over the secure network 403.For example, the initializing cryptographic chip 614 can be from the Atmel family of crypto-authentication chips including the ATAES132A, the ATECC108A, the ATSHA204A, or the ATECC508A.","The initializing cryptographic chip 614 can implement a variety of security models including the Advanced Encryption Standard (AES), Elliptical curve cryptography (ECC), Elliptic Curve Diffie-Hellman (ECDH), or a combination thereof.","The term cryptographic chip can include the adapter cryptographic chip 302, the programming cryptographic chip 412, or the initializing cryptographic chip 614.The adapter cryptographic chip 302, the programming cryptographic chip 412, or the initializing cryptographic chip 614 can be the same cryptographic chip type for proper interoperation between the cryptographic chips.","The security key instantiation controller 610 is used to transfer the primary key 414 to the programming cryptographic chip 412 in the automated assembly system 100 of FIG.","1 in a secure sequence.","The security key instantiation controller 610 can selectively initialize the primary key 414 in the automated assembly system 100, the socket adapters 206, or the combination thereof.","The security key instantiation controller 610 can provision the device programming system 201 with the primary key 414 by initializing the primary key 414 in the programming cryptographic chip 412.The security key instantiation controller 610 can provision the socket adapters 206 with the primary key 414 by initializing the primary key 414 in the adapter cryptographic chip 302.The manufacturer security database can be accessed by the control processor 612.The operator console 401 can initiate the key instantiation process.","An operator can log into the operator console 401 after being authenticated on the operator console 401.An uninitiated one of the automated assembly system 100 having one or more of the socket adapters 206 that are uninitiated and can be coupled to the security key instantiation controller 610.Referring now to FIG.","7, therein is shown an exemplary process flow of the operation of the security provisioning system 602 of FIG.","6.The security provisioning system 602 can initialize one of the automated assembly system 100 of FIG.","1.For example, the initialization process can provision the automated assembly system 100 by configuring the programming cryptographic chip 412 of FIG.","4 with a unique value of the primary key 414 of FIG.","4.Once the programming cryptographic chip 412 is configured with the primary key 414, the primary key 414 cannot be access from outside the programming cryptographic chip 412.In another example, the security provisioning system 602 can configure the adapter cryptographic chip 302 of FIG.","3 of one of the socket adapters 206 of FIG.","2 attached to the device programming system 201 of FIG.","2.Configuring the adapter cryptographic chip 302 includes storing the primary key 414 in the adapter cryptographic chip 302.In an operator step 702, the operator authenticates through the operator console 401 of FIG.","4, to the secure network 403 of FIG.","4 as the operator who is authorized to manufacture new boards.","The manufacturing security database 616 of FIG.","6 is owned and managed by the intellectual property (IP) owner or and not the client factory.","The manufacturing security database 616 records all the details of the provisioning activity.","In a request step 704, the operator is authenticated and the control processor 612 of FIG.","6 executing the factory software package requests the security key instantiation controller 610 of FIG.","6 to transfer the primary key 414 to the uninitiated one of the automated assembly system 100 or the uninitiated one of the socket adapters 206.The security key instantiation controller 610 can also be known as the golden controller.","In a communication step 706, the communication between the security key instantiation controller 610 and the automated assembly system 100 is session based using random numbers to uniquely identify the session and targeted between the initializing the adapter cryptographic chip 302 of FIG.","3 as identified by a specific one of the adapter identifier 306 of FIG.","3.Thus, the communication is protected from security breaches, such as replay attack or man-in-the middle attack.","In an authentication step 708, the programming cryptographic chip 412 of the uninitiated one of the automated assembly system 100 receives the primary key hash 320 of FIG.","3 communication and reads the adapter identifier 306, the primary key 414 is established and cannot be changed or accessed.","Again, at no point in this process is the primary key 414 transferred through the communication.","The security key instantiation controller 610 is only initialized once.","The generation of a master key 620 of FIG.","6 within the security key instantiation controller 610 is performed by the secure bootstrap firmware 604 of FIG.","6, which instructs the initializing cryptographic chip 614 of FIG.","6 to self-generate a random key and save it as the master key 620 that can only be used by the initializing cryptographic chip 614, but never made available for outside access.","The master key 620 can be the primary key 414 of the programming cryptographic chip 412.Once this is done, the security key instantiation controller 610 becomes the reference controller 618 of FIG.","6, from which all of the automated assembly system 100 or the socket adapters 206 are spawned.","The security key instantiation controller 610 can encoded the programming system identifier 220 of FIG.","2 with the primary key 414 and send it to the device programming system 201.The programming cryptographic chip 412 can decode the primary key 414 using the programming system identifier 220 and store the received encoded version of the primary key 414 inside the programming cryptographic chip 412.In another example, the security key instantiation controller 610 can encode the programming processor 218 of FIG.","2 can send the primary key 414 with both the programming system identifier 220 and adapter identifier 306 of one of the socket adapters 206 and send it to the device programming system 201.The programming process 218 and the programming cryptographic chip 412 can send the encrypted value to the appropriate one of the socket adapters 206 which can then use the adapter cryptographic chip 302 to decode the primary key 414 internally using the adapter identifier 306 and the programming system identifier 220.The primary key 414 is then stored internally within the adapter cryptographic chip 302 and not made accessible from outside the adapter cryptographic chip 302.It has been discovered that the security provisioning system 602 can self-generate and instantiate the master key 620 in the automated assembly system 100, the socket adapters 206, or the combination thereof.","The process of instantiating the master key 620 in the automated assembly system 100 or the socket adapters 206, never exposes the master key 620 to the outside of the initializing cryptographic chip 614 by keeping the primary key 414 in hardware so it can never be seen but only can be used cryptographically to authenticate other devices, using latest hardware capabilities in a novel way.","It has been discovered that provisioning the device programming system 201 with the primary key 414 via the secure network 403 of FIG.","4 improves the level of security of the device programming system 201 of FIG.","2 by enabling the authentication of the socket adapters 206.By matching the primary key hash 320 and the adapter hash 321 of FIG.","3, the device programming system 201 can insure that the correct ones of the socket adapters 206 are being used during operation.","It has been discovered that provisioning the socket adapters 206 with the primary key 414 via the secure network 403 improves the level of security of the device programming system 201 by enabling the authentication of the socket adapters 206.By calculating the adapter hash 321 based on the primary key 414 and the adapter identifier 306, the device programming system 201 can insure that the correct ones of the socket adapters 206 are being used during operation.","It has been discovered that provisioning the socket adapters 206 with the primary key 414 encrypted using the programming system identifier 220 and the adapter identifier 302 improves the level of security of the device programming system 201 by enabling the authentication of the socket adapters 206 and keeping the primary key 414 hidden from view.","By decrypting the primary key 414 using the programming system identifier 220 and the adapter identifier 306, the device programming system 201 can insure that the correct ones of the socket adapters 206 are being used during operation.","Referring now to FIG.","8, therein is shown a flow chart for an automated manufacturing system 800 for operating the automated manufacturing system 800 in accordance with an alternative embodiment of the present invention.","The automated manufacturing system 800 includes detecting a socket adapter having an adapter identifier and an adapter cryptographic chip in a block 802; calculating a primary key hash based on a primary key in a programming cryptographic chip in a block 804; calculating an adapter hash based on the adapter identifier using the adapter cryptographic chip in a block 806; matching the primary key hash to the adapter hash to update an authentication token with the adapter identifier for authenticating the socket adapter on the device programming system in a block 808; and programming programmable devices in the socket adapter based on the authentication token in a block 810.It has been discovered that the present invention thus has numerous aspects.","The present invention valuably supports and services the historical trend of reducing costs, simplifying systems, and increasing performance.","These and other valuable aspects of the present invention consequently further the state of the technology to at least the next level.","The resulting processes and configurations are straightforward, cost-effective, uncomplicated, highly versatile and effective, can be surprisingly and unobviously implemented by adapting known technologies, and are thus readily suited for efficiently and economically configuring programmable devices fully compatible with conventional manufacturing processes and technologies.","While the invention has been described in conjunction with a specific best mode, it is to be understood that many alternatives, modifications, and variations will be apparent to those skilled in the art in light of the aforegoing description.","Accordingly, it is intended to embrace all such alternatives, modifications, and variations, which fall within the scope of the included claims.","All matters hithertofore set forth herein or shown in the accompanying drawings are to be interpreted in an illustrative and non-limiting sense."]],"string":"[\n [\n \"AUTOMATED MANUFACTURING SYSTEM WITH ADAPTER SECURITY MECHANISM AND METHOD OF MANUFACTURE THEREOF\",\n \"A method of operation of an automated assembly system includes: detecting a socket adapter having an adapter identifier and an adapter cryptographic chip; calculating a primary key hash based on a primary key in a programming cryptographic chip; calculating an adapter hash based on the adapter identifier using the adapter cryptographic chip; matching the primary key hash to the adapter hash to update an authentication token with the adapter identifier for authenticating the socket adapter on the device programming system; and programming programmable devices in the socket adapter based on the authentication token.\"\n ],\n [\n \"1.A method of operation of a security provisioning system comprising: calculating an adapter digital signature based on an adapter identifier using an adapter cryptographic chip on a socket adapter; calculating a programmer digital signature based on the adapter identifier using a programming cryptographic chip of a device programming system; authenticating the socket adapter by matching the adapter digital signature to the programmer digital signature; and programming programmable devices in the socket adapter upon authentication of the of the socket adapter.\",\n \"2.The method as claimed in claim 1 wherein calculating the adapter digital signature includes calculating the adapter digital signature based on the adapter identifier and a primary key.\",\n \"3.The method as claimed in claim 1 wherein the calculating the programmer digital signature includes calculating the programmer digital signature using a primary key and the adapter identifier retrieved from the socket adapter.\",\n \"4.The method as claimed in claim 1 wherein authenticating the socket adapter includes comparing an adapter hash generated by the adapter cryptographic chip to a primary key hash generated by the programming cryptographic chip.\",\n \"5.The method as claimed in claim 1 further comprising preventing the programming of the programmable devices upon the failure of the authentication of the socket adapter.\",\n \"6.A method of operation of a security provisioning system comprising: encoding a primary key inside an adapter cryptographic chip and a programming cryptographic chip; calculating an adapter digital signature based on an adapter identifier and the primary key using the adapter cryptographic chip on a socket adapter; calculating a programmer digital signature based on the adapter identifier and the primary key using the programming cryptographic chip of a device programming system; authenticating the socket adapter by matching the adapter digital signature to the programmer digital signature; and programming programmable devices in the socket adapter upon authentication of the of the socket adapter.\",\n \"7.The method as claimed in claim 6 wherein calculating the adapter digital signature includes calculating the adapter digital signature using an advanced encryption standard method, an elliptical curve method, or a combination thereof.\",\n \"8.The method as claimed in claim 6 wherein programming the programmable devices includes programming the programmable devices in a destination socket of the socket adapter.\",\n \"9.The method as claimed in claim 6 wherein encoding the primary key includes receiving the primary key from a security key instantiation controller over a secure network.\",\n \"10.The method as claimed in claim 6 wherein encoding the primary key includes transferring the primary key from a security key instantiation controller to the programming cryptographic chip.\",\n \"11.A security provisioning system comprising: a socket adapter having an adapter identifier; an adapter cryptographic chip on the socket adapter, for calculating an adapter digital signature based on the adapter identifier; a programming cryptographic chip in a device programming system, coupled to the socket adapter, for calculating a programmer digital signature based on the adapter identifier; and a programming processor, coupled to the device programming system, for authenticating the socket adapter by matching the adapter digital signature to the programmer digital signature and programming programmable devices in the socket adapter upon authentication of the socket adapter.\",\n \"12.The system as claimed in claim 11 wherein the adapter digital signature is based on the adapter identifier and the primary key.\",\n \"13.The system as claimed in claim 11 wherein the programmer digital signature is calculated using a primary key and the adapter identifier retrieved from the socket adapter.\",\n \"14.The system as claimed in claim 11 wherein the adapter cryptographic chip is for comparing an adapter hash generated by the adapter cryptographic chip to a primary key hash generated by the programming cryptographic chip.\",\n \"15.The system as claimed in claim 11 wherein the programming processor is for preventing the programming of the programmable devices upon the failure of the authentication of the socket adapter.\",\n \"16.The system as claimed in claim 11 wherein the primary key is encoded inside the adapter cryptographic chip and the programming cryptographic chip.\",\n \"17.The system as claimed in claim 16 wherein the adapter digital signature is calculated using an advanced encryption standard system, an elliptical curve system, or a combination thereof.\",\n \"18.The system as claimed in claim 16 wherein the socket adapter includes a destination socket for programming the programmable devices.\",\n \"19.The system as claimed in claim 16 further comprising a secure network for transferring the primary key from a security key instantiation controller to the device programming system.\",\n \"20.The system as claimed in claim 16 further comprising a security key instantiation controller transferring the primary key to the programming cryptographic chip.\"\n ],\n [\n \" BACKGROUND ART Most of the world's electronic manufacturers do not possess the ability to build highly proficient multi-module automated processing systems, such as a manufacturing system that contain fully integrated robotics systems.\",\n \"There is a desire to standardize manufacturing processes across multiple manufacturing sites world-wide.\",\n \"In order to reduce development costs some manufacturers have reverse engineered manufacturing devices.\",\n \"The risks of exposure or proprietary manufacturing processes and client intellectual property can restrict product manufacturing to dedicated sites utilizing certified assembly devices.\",\n \"This can restrict the available volumes of products without regard to potential increased demand and dwindling supplies.\",\n \"Some manufacturing capacity can be underutilized because the required processes and intellectual property cannot be transferred to additional sites.\",\n \"The exposure or loss of the manufacturing process or the client intellectual property is too great for unsecured movement between manufacturing facilities.\",\n \"Compromise of the manufacturing process or the client's intellectual property can represent a business calamity that could ruin the manufacturer's reputation and risk future business opportunity.\",\n \"Thus, a need still remains for an automated manufacturing system with adapter security that can effectively protect the manufacturing process and the client's intellectual property, while being able to distribute the workload across multiple sites as required to meet the client's manufacturing needs.\",\n \"In view of the ever-increasing need to save costs and improve efficiencies, it is more and more critical that answers be found to these problems.\",\n \"Solutions to these problems have been long sought but prior developments have not taught or suggested any solutions and, thus, solutions to these problems have long eluded those skilled in the art.\"\n ],\n [\n \" BRIEF DESCRIPTION OF THE DRAWINGS FIG.\",\n \"1 is a functional block diagram of an automated assembly system in accordance with an embodiment of the present invention; FIG.\",\n \"2 is an isometric view of a device programming system; FIG.\",\n \"3 is an isometric view of one of the socket adapters; FIG.\",\n \"4 is a functional block diagram of an adapter security system; FIG.\",\n \"5 is an exemplary process flow of the operation of the adapter security system; FIG.\",\n \"6 is a functional block diagram of a security provisioning system; FIG.\",\n \"7 is an exemplary process flow of the operation of the security provisioning system; and FIG.\",\n \"8 is a flow chart of an automated manufacturing system for operating the automated manufacturing system in accordance with an alternative embodiment of the present invention.\",\n \"detailed-description description=\\\"Detailed Description\\\" end=\\\"lead\\\"?\"\n ],\n [\n \"CROSS-REFERENCE TO RELATED APPLICATION(S) This application claims benefit as a Continuation of U.S. application Ser.\",\n \"No.\",\n \"14/921,833, filed Oct. 23, 2015, which claims the benefit of U.S.\",\n \"Provisional Patent Application Ser.\",\n \"No.\",\n \"62/098,257 filed Dec. 30, 2014, the entire contents of the aforementioned are hereby incorporated by reference as if fully set forth herein, under 35 U.S.C.\",\n \"§ 120.The applicant(s) hereby rescind any disclaimer of claim scope in the parent application(s) or the prosecution history thereof and advise the USPTO that the claims in this application may be broader than any claim in the parent application(s).\",\n \"TECHNICAL FIELD The present invention relates generally to automated systems, and more particularly to automated manufacturing systems with adapter security mechanism for manufacturing operations.\",\n \"BACKGROUND ART Most of the world's electronic manufacturers do not possess the ability to build highly proficient multi-module automated processing systems, such as a manufacturing system that contain fully integrated robotics systems.\",\n \"There is a desire to standardize manufacturing processes across multiple manufacturing sites world-wide.\",\n \"In order to reduce development costs some manufacturers have reverse engineered manufacturing devices.\",\n \"The risks of exposure or proprietary manufacturing processes and client intellectual property can restrict product manufacturing to dedicated sites utilizing certified assembly devices.\",\n \"This can restrict the available volumes of products without regard to potential increased demand and dwindling supplies.\",\n \"Some manufacturing capacity can be underutilized because the required processes and intellectual property cannot be transferred to additional sites.\",\n \"The exposure or loss of the manufacturing process or the client intellectual property is too great for unsecured movement between manufacturing facilities.\",\n \"Compromise of the manufacturing process or the client's intellectual property can represent a business calamity that could ruin the manufacturer's reputation and risk future business opportunity.\",\n \"Thus, a need still remains for an automated manufacturing system with adapter security that can effectively protect the manufacturing process and the client's intellectual property, while being able to distribute the workload across multiple sites as required to meet the client's manufacturing needs.\",\n \"In view of the ever-increasing need to save costs and improve efficiencies, it is more and more critical that answers be found to these problems.\",\n \"Solutions to these problems have been long sought but prior developments have not taught or suggested any solutions and, thus, solutions to these problems have long eluded those skilled in the art.\",\n \"DISCLOSURE OF THE INVENTION The embodiments of the present invention provides a method of operation of an automated assembly system including: detecting a socket adapter having an adapter identifier and an adapter cryptographic chip; calculating a primary key hash based on a primary key in a programming cryptographic chip; calculating an adapter hash based on the adapter identifier using the adapter cryptographic chip; matching the primary key hash to the adapter hash to update an authentication token with the adapter identifier for authenticating the socket adapter on the device programming system; and programming programmable devices in the socket adapter based on the authentication token.\",\n \"The embodiments of the present invention provides an automated manufacturing system, which includes: a socket adapter having an adapter identifier; a programming cryptographic chip, coupled to the socket adapter, for calculating a primary key hash based on a primary key; an adapter cryptographic chip, coupled to the socket adapter, for calculating an adapter hash based on the adapter identifier; and a programming processor, coupled to the programming cryptographic chip, for matching the primary key hash to the adapter hash to update an authentication token with the adapter identifier for authenticating the socket adapter to enable programming programmable devices in the socket adapter based on the authentication token.\",\n \"Certain embodiments of the invention have other steps or elements in addition to or in place of those mentioned above.\",\n \"The steps or element will become apparent to those skilled in the art from a reading of the following detailed description when taken with reference to the accompanying drawings.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS FIG.\",\n \"1 is a functional block diagram of an automated assembly system in accordance with an embodiment of the present invention; FIG.\",\n \"2 is an isometric view of a device programming system; FIG.\",\n \"3 is an isometric view of one of the socket adapters; FIG.\",\n \"4 is a functional block diagram of an adapter security system; FIG.\",\n \"5 is an exemplary process flow of the operation of the adapter security system; FIG.\",\n \"6 is a functional block diagram of a security provisioning system; FIG.\",\n \"7 is an exemplary process flow of the operation of the security provisioning system; and FIG.\",\n \"8 is a flow chart of an automated manufacturing system for operating the automated manufacturing system in accordance with an alternative embodiment of the present invention.\",\n \"BEST MODE FOR CARRYING OUT THE INVENTION The following embodiments are described in sufficient detail to enable those skilled in the art to make and use the invention, and it is to be understood that other embodiments would be evident based on the present disclosure and that process or mechanical changes may be made without departing from the scope of the present invention.\",\n \"In the following description, numerous specific details are given to provide a thorough understanding of the invention.\",\n \"However, it will be apparent that the invention may be practiced without these specific details.\",\n \"In order to avoid obscuring the present invention, some well-known system configurations, and process steps are not disclosed in detail.\",\n \"Likewise, the drawings showing embodiments of the invention are semi-diagrammatic and not to scale and, particularly, some of the dimensions are for the clarity of presentation and are shown exaggerated in the drawing FIG's.\",\n \"In addition, where multiple embodiments are disclosed and described having some features in common, for clarity and ease of illustration, description, and comprehension thereof, similar and like features one to another will ordinarily be described with like reference numerals.\",\n \"The term “horizontal” as used herein is defined as a plane parallel to the plane or surface of the operating plane of an automated assembly system, regardless of its orientation.\",\n \"The term “vertical” refers to a direction perpendicular to the horizontal as just defined.\",\n \"Terms, such as “on”, “above”, “below”, “bottom”, “top”, “side” (as in “sidewall”), “higher”, “lower”, “upper”, “over”, and “under”, are defined with respect to the horizontal plane.\",\n \"Referring now to FIG.\",\n \"1, therein is shown a functional block diagram of an automated assembly system 100 in accordance with an embodiment of the present invention.\",\n \"The automated assembly system 100 is a mechanism for configuring programmable devices.\",\n \"The automated assembly system 100 can include a system controller 110 and one or more assembly devices 108.The automated assembly system 100 can be configured to accept modules with an intelligent design.\",\n \"These intelligently designed modules are configured to interface with the automated assembly system 100.The automated assembly system 100, can be an automated programming system, can immediately recognizes module information such as the identification of the module, the type of module, the configuration of the module, the geometry of the module, and the location of the module within the system or feeder bank.\",\n \"For example, configuration information about the assembly devices that, can be programming modules, provide socket count, socket pitch, socket offset, socket location, and the number of programming sites.\",\n \"On the other hand, an intelligently designed tape module may simply provide information about the pocket offset.\",\n \"The automated assembly system 100 can include a backplane 112, a first intelligent module 114, a second intelligent module 116, an Nth intelligent module 118, and the system controller 110.The backplane provides a data, control, and power, communication interface for the smart interface system.\",\n \"For example, the backplane may provide a transmission interface for the first intelligent module, the second intelligent module, and the Nth intelligent module, wherein the Nth intelligent module represents any module number greater than one.\",\n \"It is understood that the automated assembly system 100 can include any number of the intelligent modules and each of the intelligent modules can control the assembly devices 108.Each of the modules contains a data port 122, a control port 124, and a power port 126.The control port 124 can be used to transmit commands to and status between the modules.\",\n \"For example, track identification information, such as the physical location of each module, can be transferred through the control port 124.The data port 122 can be used to broadcast device image data, send commands, and receive status information for programming operations.\",\n \"Due to the volume of data transmitted by the data port 122, a high-speed port, such as an Ethernet connection is usually employed.\",\n \"Any module that would require the transmission of large amounts of data could use the data port 122.The power port 126 transmits power to each module through the backplane.\",\n \"The power supplied to each module via the power port 126 can be electrical, but in principle, it could be mechanical, pneumatic, hydraulic, magnetic, optical, chemical, or a combination thereof.\",\n \"The data port 122, the control port 124, and the power port 126 are collectively referred to as a composite connection 128.As the composite connection 128 may protrude from the module, a mechanical protection scheme can be designed to protect it from accidental damage.\",\n \"The composite connection 128 may also employ a hardware based naming format.\",\n \"This format will allow configurable hardware switches on each module that not only differentiate by the type of module, but also by a module serial number of each module.\",\n \"The composite connection 128, when coupled to the smart interface system, may employ a mechanical fit connection that consists of pins and spring-loaded washers.\",\n \"Each module may use an identical set pitch for the composite connection 128 pins.\",\n \"This type of configuration provides for uniform mounting and consistent registration for each of the composite connection 128.Additionally, the pin and spring loaded washer type of connection establishes a reliable and repeatable tool-less installation that requires minimal time.\",\n \"Each module can be installed by merely establishing preliminary contact and then registering or locking in place.\",\n \"The data port 122, the control port 124 and the power port 126 of each one of the modules is coupled with a central control 130, a robot control 132, and a local power 134, respectively, within the system controller 110.The system controller 110 acts as a processing component for receiving and transmitting information between the non-text user interface system and each of the modules.\",\n \"Each of the control port 124 includes a track information system for communicating track identification information with the backplane.\",\n \"The track identification information may include a unique identification number and a unique location designation.\",\n \"For example, the first intelligent module, the second intelligent module, and the Nth intelligent module each possess the ability to transmit track information.\",\n \"A software protocol 136 that delivers information through the data port 122 and the control port 124 is a bi-directional protocol.\",\n \"For example, the data port 122 can use an Ethernet port and the control port 124 can use a Controller Area Network (CAN) port with a hard coded segment for carrying track identification information.\",\n \"This bi-directional protocol allows for data and controls (digital and analog) communication.\",\n \"Each module may use this common protocol to enhance interchangeability within the system.\",\n \"The software protocol 136 can also employ a multiple master system, which allows any component within the automated manufacturing system to request or send data.\",\n \"For example, the input module could request data from one of the programming modules without any need for the robot control 132 within the system controller 110 to initiate a transverse request.\",\n \"The software protocol 136 also includes a messaging system 138, which can relay information between components.\",\n \"For example, the messaging system 138 can relay information about whether or not the adapters are open or closed, and what type of modules are installed within the system.\",\n \"The messaging system 138 may include a prioritized messaging system, wherein both of these systems are based on the Controller Area Network (CAN) protocol.\",\n \"The present invention employs a unique set of CAN messages.\",\n \"All messages within the CAN system are based on a message number, with lower numbered messages receiving the higher priority.\",\n \"So, if two messages are sent simultaneously, the message with the lowest value will get through, and the other message will have to wait to be retransmitted at a later date.\",\n \"Any cryptographic solution involves a secret key, such as a primary key or a root key.\",\n \"The biggest issue with keys is how to keep them as a secret.\",\n \"Usually software embeds the key in some obscure needle in the hay stack model.\",\n \"Using today's supercomputers, these are easily breakable.\",\n \"The current system insures no one ever knows the primary key.\",\n \"It is never kept in any software.\",\n \"No one really knows the key, not even the developers who coded the software.\",\n \"The key is kept in hardware and could never be read out.\",\n \"It can only be used internally to an integrated circuit for cryptographic operations.\",\n \"Referring now to FIG.\",\n \"2, therein is shown an isometric view of a device programming system 201.The device programming system 201 can include a programming processor 218, an input device receptacle 204, socket adapters 206, destination sockets 208, a device placement unit 210, programmable devices 212, and an output device receptacle 214.The device programming system 201 can be the automated assembly system 100 of FIG.\",\n \"1.The automated assembly system 100 is a mechanism for configuring programmable devices 212.The automated assembly system 100 can configure the programmable devices 212 by initializing and writing a data image into the programmable devices 212.The programmable devices 212 can include Flash memory devices, programmable read-only memory, hybrid devices having processing and memory elements, or a combination thereof.\",\n \"The automated assembly system 100 can include the system controller 110 of FIG.\",\n \"1 and one or more of the assembly devices 108 of FIG.\",\n \"1.Each of the assembly devices 108 can configure and program one or more of the programmable devices 212.The device programming system 201 is a device for configuring the programmable devices 212.The device programming system 201 can load an entire chip image at a time and then configure the programmable devices 212.Configuring is defined as writing control and data information to the programmable devices 212.Configuring the programmable devices 212 can store memory structure, cryptographic data, and user data on the programmable devices 212.Configuring can include forming one-time structures such as partitions on the programmable devices 212.The device programming system 201 can include the programming processor 218.The programming processor 218 is a computing unit for controlling the device programming system 201.The programming processor 218 can include a central processing unit (not shown), a local storage unit 203, a communication interface (not shown), and a software (not shown).\",\n \"The programming processor 218 can have a variety of configurations.\",\n \"For example, the programming processor 218 can include the system controller 110 or be coupled to the system controller 110.The programming processor 218 can be a single processor, a multiprocessor, a cloud computing element, or a combination thereof.\",\n \"The local storage unit 203 is a device for storing and retrieving information.\",\n \"For example, the local storage unit 203 of the device programming system 201 can be a disk drive, a solid-state memory, an optical storage device, or a combination thereof.\",\n \"The software is control information for executing on the control unit.\",\n \"The software can be used to control the functionality of the device programming system 201.The device programming system 201 can include the input device receptacle 204 and the output device receptacle 214.The input device receptacle 204 is a source of the programmable devices 212.For example, the input device receptacle 204 can be a tray that conforms to the Joint Electron Device Engineering Council (JEDEC) standards.\",\n \"The input device receptacle 204 can be used for holding unprogrammed devices.\",\n \"The output device receptacle 214 is a destination for the programmable devices 212 that have been processed.\",\n \"For example, the output device receptacle 214 can be an empty JEDEC tray for holding finished devices.\",\n \"The device programming system 201 can include the socket adapters 206 having the destination sockets 208.The socket adapters 206 are mechanisms for holding and managing sockets.\",\n \"The sockets are mechanisms for holding and interfacing with the programmable devices 212.The socket adapters 206 are modular and can be removed from the device programming system 201 to accommodate different socket configurations.\",\n \"For example, the socket adapters 206 can include a latch mechanism (not shown) for attaching to the device programming system 201.The socket adapters 206 are secure devices that can authenticate themselves with the device programming system 201 using a cryptographic challenge process to allow access to the socket adapters 206.The socket adapters 206 are described in greater detail below.\",\n \"The destination sockets 208 can hold the programmable devices 212.In general, the destination sockets 208 can be used to read or write new information to one of the programmable devices 212.The device programming system 201 can include the device placement unit 210.The device placement unit 210 is a mechanism for positioning a programmable device in one of the destination sockets 208.The device placement unit 210 can be implemented in a variety of ways.\",\n \"For example, the device placement unit 210 can be a robotic arm, a pick and place mechanism, or a combination thereof.\",\n \"Although the device placement unit 210 is described as a rail-based positioning system, it is understood that any system capable of positioning one of the programmable devices 212 in the destination sockets 208 can be used.\",\n \"The device placement unit 210 can retrieve one or more of the programmable devices 212 that are blank from the input device receptacle 204.The device placement unit 210 can transport the programmable devices 212 to the destination sockets 208 of the socket adapters 206.Once the programmable devices 212 are engaged and secured by the socket adapters 206, the device programming process can begin.\",\n \"The device programming system 201 can program a local copy of the information into the programmable devices 212 in one of the destination sockets 208.For example, the local copy of the programming information can be in a pre-programmed master device, from a file in local storage, or from a remote server.\",\n \"Once programming is complete, the device placement unit 210 can transport the programmable devices 212 that have been programmed to the output device receptacle 214.The device placement unit 210 can transports any of the programmable devices 212 that have errors to a reject bin (not shown).\",\n \"The automated assembly system 100 can include an automatic receptacle mapping feature 216.The automatic receptacle mapping feature 216 will automatically measure the physical characteristics and connector geometry of the programmable devices, such as the number of rows and columns, the row offset and pitch, and the column offset and pitch.\",\n \"These automatic measurements provide information about the exact coordinates, for example X, Y, Z, and theta directions or sometimes only X and Y directions for each center of pocket within each receptacle.\",\n \"This can include the location for each device.\",\n \"The automatic receptacle mapping feature 216 employs optical methods based upon, changes of state, such as reflectivity, and specifically designed algorithms to calculate receptacle location, geometry and physical characteristics.\",\n \"This mapping feature is designed in such a way that the operator no longer has to manually enter in the physical characteristics and geometry of the programmable device and the destination sockets 208, which saves the operator time and prevents operator input error.\",\n \"The automated assembly system 100 can include a programming system identifier 220.The programming system identifier 220 is a unique value for each particular one the device programming system 201.The programming system identifier 220 can be used to uniquely identify each one of the device programming system 201.Referring now to FIG.\",\n \"3, therein is shown an isometric view of one of the socket adapters 206.The socket adapters 206 can include an adapter cryptographic chip 302, an adapter base 304, and one or more of the destination sockets 208 for retaining the programmable devices 212 of FIG.\",\n \"2.Each of the socket adapters 206 can include an adapter identifier 306.The adapter identifier 306 is a unique number associated with each one of the socket adapters 206.For example, the adapter identifier 306 can be a serial number, a part number, a random number, a calculated cryptographic key, or a combination thereof.\",\n \"The adapter cryptographic chip 302 is an electronic component for performing crypto-authentication.\",\n \"The adapter cryptographic chip 302 can respond to a cryptographic challenge 328 by calculating a response key 326.The response key 326 can be based on the adapter identifier 306 of one of the socket adapters 206.The cryptographic challenge 328 is described in greater detail below.\",\n \"For example, the adapter cryptographic chip 302 can be from the Atmel family of crypto-authentication chips including the ATAES132A, the ATECC108A, the ATSHA204A, or the ATECC508A.\",\n \"The adapter cryptographic chip 302 can implement a variety of security models including the Advanced Encryption Standard (AES), Elliptical curve cryptography (ECC), Elliptic Curve Diffie-Hellman (ECDH), or a combination thereof.\",\n \"The socket adapters 206 can have a variety of configuration.\",\n \"For example, the socket adapters 206 can include four of the destination sockets 208 for configuring the programmable devices 212.Although the socket adapters 206 are shown with four sockets, it is understood that the socket adapters 206 any number and combination of the destination sockets 208.The destination sockets 208 can be used for reading and writing the programmable devices 212.The destination sockets 208 can be used to read from a pre-programmed device.\",\n \"The destination sockets 208 are only used to configure the programmable devices 212 that are blank or unprogrammed.\",\n \"The destination sockets 208 of the socket adapters 206 can be coupled to the device programming system 201 of FIG.\",\n \"2 with contacts (not shown) on the top and bottom of the socket adapters 206.The device programming system 201 can access to the adapter cryptographic chip 302 via the contacts for authentication of the socket adapters 206.Referring now to FIG.\",\n \"4, therein is shown a functional block diagram of an adapter security system 402.The functional block diagram depicts an operator console 401 having an authentication manager software 404 coupled to the automated assembly system 100 of FIG.\",\n \"1 over a secure network 403.The automated assembly system 100 of FIG.\",\n \"1 can include the device programming system 201 of having one or more of the socket adapters 206.The automated assembly system 100 can include the device programming system 201 having one or more of the socket adapters 206.The device programming system 201 can include a programming processor 218 running a programming firmware 410.The programming processor 218 is coupled to a cryptographic chip, such as a programming cryptographic chip 412.For example, the cryptographic chip can be from the Atmel family of crypto-authentication chips including the ATAES132A, the ATECC108A, the ATSHA204A, or the ATECC508A.\",\n \"The cryptographic chip can implement a variety of security models including the Advanced Encryption Standard (AES), Elliptical curve cryptography (ECC), Elliptic Curve Diffie-Hellman (ECDH), or a combination thereof.\",\n \"The programming cryptographic chip 412 can include an internal copy of a primary key 414.The primary key 414 can be a master trusted root key or other unique cryptographic key.\",\n \"The primary key 414 is a unique value associated with the automated assembly system 100 that can be used to validate the trust relationship between entities.\",\n \"The primary key 414 is described in greater detail below.\",\n \"The programming cryptographic chip 412 can be provisioned and assigned the primary key 414 in an initialization process.\",\n \"Once the programming cryptographic chip 412 has been configured with the primary key 414, the primary key 414 is stored in an area of internal memory that cannot be accessed from outside the programming cryptographic chip 412.The primary key 414 is a unique identifier to identify the individual automated assembly system 100.Each one of the individual automated assembly system 100 can have a unique value for the primary key 414.The automated assembly system 100 can be deployed in a facility controlled by a client.\",\n \"The automated assembly system 100 can be used to configure programmable devices installed in the socket adapters 206.However, the automated assembly system 100 will authenticate each of the socket adapters 206 by indirectly comparing the value of the primary key 414 with the value of the adapter identifier 306.The automated assembly system 100 can authenticate the socket adapters 206 using an assembly level challenge 418.In the assembly level challenge 418, the adapter security system 402 can authenticate each of the socket adapters 206 by comparing a primary key hash 320 with an adapter hash 321.The programming cryptographic chip 412 can calculate the primary key hash 320 and the adapter cryptographic chip 302 of FIG.\",\n \"3 can calculate the adapter hash 321.The two hash values are compared and one of the socket adapters 206 is authenticated if the two hash values match.\",\n \"The primary key hash 320 is a calculated value based on the primary key 414 and the adapter identifier 306 of the socket adapters 206.The primary key 414 remains securely stored internally within the programming cryptographic chip 412 and cannot be directly accessed from outside any of the programming cryptographic chip 412.The primary key hash 320 can be calculated by the programming cryptographic chip 412 by submitting the adapter identifier 306 of one of the socket adapters 206 to the programming cryptographic chip 412.The primary key hash 320 is internally calculated by the programming cryptographic chip 412 and is based on the primary key 414 and the adapter identifier 306.The adapter identifier 306 can be retrieved from the socket adapters 206.The adapter security system 402 can calculate the adapter hash 321 by interrogating the adapter cryptographic chip 302 of one of the socket adapters 206.Each of the socket adapters 206 can include an internal copy of the primary key 414 stored within the adapter cryptographic chip 302.The programming firmware 410 can send a command or the cryptographic challenge 328 of FIG.\",\n \"3 to the socket adapters 206 instructing the adapter cryptographic chip 302 to calculate the adapter hash 321.The adapter hash 321 is based on the internally stored copy of the primary key 414 in the adapter cryptographic chip 302 and the adapter identifier 306.The programming processor 218 running the programming firmware 410 can compare the primary key hash 320 and the adapter hash 321 and if the values match, then the selected one of the socket adapters 206 is authenticated.\",\n \"When one of the socket adapters 206 has been authenticated, then the adapter security system 402 can enable one of the socket adapters 206 for operation.\",\n \"If one of the socket adapters 206 is unauthenticated, then the adapter security system 402 can prevent the use of the one of the socket adapters 206 that has failed authentication.\",\n \"The programming processor 218 can execute the programming firmware 410 to request the calculation of the primary key hash 320 by the programming cryptographic chip 412 and request the calculation of the adapter hash 321 based on the adapter identifier 306.The programming processor 218 can then compare the primary key 414 and the adapter hash 321 to authenticate the socket adapters 206.If the hashes match, then the automated assembly system 100 can program the programmable devices 212 of FIG.\",\n \"2 coupled to the socket adapters 206.By only comparing the primary key hash 320 and the adapter hash 321, the primary key 414 can remained hidden and is not exposed outside the cryptographic chips.\",\n \"Authentication of the socket adapter 206 allows the socket adapter 206 to be used by the device programming system 201.For example, matching the primary key hash 320 to the adapter hash 321 can set an authentication token 420 to the value of the adapter identifier 306 to indicate that the selected one of the socket adapters 206 is authenticated.\",\n \"The authentication token 420 can be a single value, a list, a matrix, a hybrid data structure, or a combination thereof.\",\n \"In an illustrative example, the device programming system 201 can detect the socket adapter 206 that is unauthorized if the adapter identifier 306 is not referenced in the authentication token 420.If the one of the socket adapters 206 is unauthorized, then the device programming system 201 can prevent access to the indicated one of the socket adapters 206.It has been discovered that authenticating one of the socket adapters 206 by calculating the primary key hash 320 and the adapter hash 321 increases security by insuring that the socket adapters 206 are authorized to operate within the device programming system 201.By verifying that the same value of the primary key 414 is in each of the cryptographic chips, secure operation can be provided.\",\n \"Referring now to FIG.\",\n \"5, therein is shown an exemplary process flow of the operation of the adapter security system 402 of FIG.\",\n \"4.The adapter security system 402 can authenticate the socket adapters 206 of FIG.\",\n \"2 by comparing the primary key hash 320 of FIG.\",\n \"3 and the adapter hash 321 of FIG.\",\n \"3 for each of the socket adapters 206.In an illustrative example, the operator console 401 of FIG.\",\n \"4 can send a request to the automated assembly system 100 of FIG.\",\n \"1 to authenticate the socket adapters 206.An authentication process for the socket adapters 206 at customer manufacturing site can be as follows: In an adapter request step 502, the authentication manager software 404 of FIG.\",\n \"4 in the operator console 401 can request the programming firmware 410 of FIG.\",\n \"4 in the programming processor 218 to authenticate one of the socket adapters 206 that has been newly inserted.\",\n \"In a programming authentication step 504, the programming firmware 410 requests the programming cryptographic chip 412 of FIG.\",\n \"4 on the system controller 110 of FIG.\",\n \"1 to authenticate the socket adapters 206 with the cryptographic challenge 328 of FIG.\",\n \"3.In an authentication sequence step 506, the programming cryptographic chip 412, which has the primary key 414 of FIG.\",\n \"4 internally, starts the cryptographic challenge 328.The cryptographic challenge 328 is an answer and response protocol used for authentication.\",\n \"For example, the actions of the authentication sequence step 506 can be as follows: 1.The device programming system 201 of FIG.\",\n \"2 can interrogate the socket adapters 206 to get the adapter identifier 306 of FIG.\",\n \"3 from one of the socket adapters 206.2.The programming processor 218 of FIG.\",\n \"2 and the programming cryptographic chip 412 can generate the assembly level challenge 418 of FIG.\",\n \"4 and send it to the socket adapters 206.3.Each of the socket adapters 206 combines the adapter identifier 306, the internal copy of the primary key 414 on-board the adapter cryptographic chip 302 of FIG.\",\n \"3, and the assembly level challenge 418 received and computes the adapter hash 321.4.The socket adapters 206 return the challenge response 322 of FIG.\",\n \"3 to the programming cryptographic chip 412 in the system controller 110.The challenge response 322 includes the adapter hash 321.5.The programming processor 218 and the programming cryptographic chip 412 extract the adapter identifier 306 by comparing the primary key hash 320 to the adapter hash 321.The adapter identifier 306 will only be correct if it was properly encoded and decoded using the same value of the primary key 414.For example, if the adapter identifier 306 decoded from the adapter hash 321 using the primary key 414 matches, then this one of the socket adapters 206 will be authenticated.\",\n \"In a matching step 508, the primary key hash 320 will only match the adapter hash 321 only if the primary key 414 on the device programming system 201 of FIG.\",\n \"2 and the unknown key of the socket adapters 206 match.\",\n \"The matching step 508 can be performed in a variety of ways.\",\n \"For example, the programming processor 218 and the programming cryptographic chip 412 can compare the primary key hash 320 and the adapter hash 321 for authentication.\",\n \"In another example, the programming processor 218 and the programming cryptographic chip 412 can extract and compare the adapter identifier 321 from each of the hashes.\",\n \"In yet another example, the device programming system 201 can extract and compare other security values encoded within both the primary key hash 320 and the adapter hash 321.The programming cryptographic chip 412 has special properties not to reveal the key, but use it only internally in the calculation of the primary key hash 320.For example, if the primary key hash 320 and the adapter hash 321 match, then the authentication token 420 of FIG.\",\n \"4 is updated with the adapter identifier 306 It has been discovered that the above communication process increases security by inhibiting code breaking processes by not exposing the primary key 414.The primary key 414 never gets exposed outside of the cryptographic chip, so monitoring the bus does not allow anyone to detect the primary key 414.It has been discovered that the above communication process prevents code breaking processes by calculating the primary key hash 320 while not exposing the primary key 414.The primary key 414 remains hidden in the programming processor 218 or the socket adapters 206, so the primary key 414 cannot be detected by hardware monitoring.\",\n \"It has been discovered that configuring the socket adapters 206 with the adapter cryptographic chip 302 can increase security by preventing the programming of the programmable devices 212 of FIG.\",\n \"2 that are not coupled to one of the socket adapters 206 that has been authenticated.\",\n \"Restricting the transfer of sensitive content or code to the programming devices 212 to only those mounted on authenticated ones of the socket adapters 206 reduces piracy and is an effective element of a comprehensive security system for programming programmable devices 212.It has been discovered that configuring the socket adapters 206 with the adapter cryptographic chip 302 can increase process integrity by allowing the tracking of the socket adapters 206 using the adapter identifier 306.Logging the adapter identifier 306 as part of the manufacturing process provides a secure audit trail to document this portion of the manufacturing process down to the adapter and device level.\",\n \"Referring now to FIG.\",\n \"6, therein is shown a functional block diagram of a security provisioning system 602.The security provisioning system 602 includes a security key instantiation controller 610 coupled to the device programming system 201.The security key instantiation controller 610 can include a control processor 612, the operator console 401, a manufacturing security database 616, a reference controller 618, a secure bootstrap firmware 604, and an initializing cryptographic chip 614.The device programming system 201 can include the programming processor 218, the programming cryptographic chip 412, the programming system identifier 220, and one or more of the socket adapters 206.Each of the socket adapters 206 includes the adapter cryptographic chip 302.Each of the socket adapters 206 can include the adapter identifier 306.The security provisioning system 602 can provision the adapter cryptographic chip 302 and the programming cryptographic chip 412 with the primary key 414 over the secure network 403.For example, the initializing cryptographic chip 614 can be from the Atmel family of crypto-authentication chips including the ATAES132A, the ATECC108A, the ATSHA204A, or the ATECC508A.\",\n \"The initializing cryptographic chip 614 can implement a variety of security models including the Advanced Encryption Standard (AES), Elliptical curve cryptography (ECC), Elliptic Curve Diffie-Hellman (ECDH), or a combination thereof.\",\n \"The term cryptographic chip can include the adapter cryptographic chip 302, the programming cryptographic chip 412, or the initializing cryptographic chip 614.The adapter cryptographic chip 302, the programming cryptographic chip 412, or the initializing cryptographic chip 614 can be the same cryptographic chip type for proper interoperation between the cryptographic chips.\",\n \"The security key instantiation controller 610 is used to transfer the primary key 414 to the programming cryptographic chip 412 in the automated assembly system 100 of FIG.\",\n \"1 in a secure sequence.\",\n \"The security key instantiation controller 610 can selectively initialize the primary key 414 in the automated assembly system 100, the socket adapters 206, or the combination thereof.\",\n \"The security key instantiation controller 610 can provision the device programming system 201 with the primary key 414 by initializing the primary key 414 in the programming cryptographic chip 412.The security key instantiation controller 610 can provision the socket adapters 206 with the primary key 414 by initializing the primary key 414 in the adapter cryptographic chip 302.The manufacturer security database can be accessed by the control processor 612.The operator console 401 can initiate the key instantiation process.\",\n \"An operator can log into the operator console 401 after being authenticated on the operator console 401.An uninitiated one of the automated assembly system 100 having one or more of the socket adapters 206 that are uninitiated and can be coupled to the security key instantiation controller 610.Referring now to FIG.\",\n \"7, therein is shown an exemplary process flow of the operation of the security provisioning system 602 of FIG.\",\n \"6.The security provisioning system 602 can initialize one of the automated assembly system 100 of FIG.\",\n \"1.For example, the initialization process can provision the automated assembly system 100 by configuring the programming cryptographic chip 412 of FIG.\",\n \"4 with a unique value of the primary key 414 of FIG.\",\n \"4.Once the programming cryptographic chip 412 is configured with the primary key 414, the primary key 414 cannot be access from outside the programming cryptographic chip 412.In another example, the security provisioning system 602 can configure the adapter cryptographic chip 302 of FIG.\",\n \"3 of one of the socket adapters 206 of FIG.\",\n \"2 attached to the device programming system 201 of FIG.\",\n \"2.Configuring the adapter cryptographic chip 302 includes storing the primary key 414 in the adapter cryptographic chip 302.In an operator step 702, the operator authenticates through the operator console 401 of FIG.\",\n \"4, to the secure network 403 of FIG.\",\n \"4 as the operator who is authorized to manufacture new boards.\",\n \"The manufacturing security database 616 of FIG.\",\n \"6 is owned and managed by the intellectual property (IP) owner or and not the client factory.\",\n \"The manufacturing security database 616 records all the details of the provisioning activity.\",\n \"In a request step 704, the operator is authenticated and the control processor 612 of FIG.\",\n \"6 executing the factory software package requests the security key instantiation controller 610 of FIG.\",\n \"6 to transfer the primary key 414 to the uninitiated one of the automated assembly system 100 or the uninitiated one of the socket adapters 206.The security key instantiation controller 610 can also be known as the golden controller.\",\n \"In a communication step 706, the communication between the security key instantiation controller 610 and the automated assembly system 100 is session based using random numbers to uniquely identify the session and targeted between the initializing the adapter cryptographic chip 302 of FIG.\",\n \"3 as identified by a specific one of the adapter identifier 306 of FIG.\",\n \"3.Thus, the communication is protected from security breaches, such as replay attack or man-in-the middle attack.\",\n \"In an authentication step 708, the programming cryptographic chip 412 of the uninitiated one of the automated assembly system 100 receives the primary key hash 320 of FIG.\",\n \"3 communication and reads the adapter identifier 306, the primary key 414 is established and cannot be changed or accessed.\",\n \"Again, at no point in this process is the primary key 414 transferred through the communication.\",\n \"The security key instantiation controller 610 is only initialized once.\",\n \"The generation of a master key 620 of FIG.\",\n \"6 within the security key instantiation controller 610 is performed by the secure bootstrap firmware 604 of FIG.\",\n \"6, which instructs the initializing cryptographic chip 614 of FIG.\",\n \"6 to self-generate a random key and save it as the master key 620 that can only be used by the initializing cryptographic chip 614, but never made available for outside access.\",\n \"The master key 620 can be the primary key 414 of the programming cryptographic chip 412.Once this is done, the security key instantiation controller 610 becomes the reference controller 618 of FIG.\",\n \"6, from which all of the automated assembly system 100 or the socket adapters 206 are spawned.\",\n \"The security key instantiation controller 610 can encoded the programming system identifier 220 of FIG.\",\n \"2 with the primary key 414 and send it to the device programming system 201.The programming cryptographic chip 412 can decode the primary key 414 using the programming system identifier 220 and store the received encoded version of the primary key 414 inside the programming cryptographic chip 412.In another example, the security key instantiation controller 610 can encode the programming processor 218 of FIG.\",\n \"2 can send the primary key 414 with both the programming system identifier 220 and adapter identifier 306 of one of the socket adapters 206 and send it to the device programming system 201.The programming process 218 and the programming cryptographic chip 412 can send the encrypted value to the appropriate one of the socket adapters 206 which can then use the adapter cryptographic chip 302 to decode the primary key 414 internally using the adapter identifier 306 and the programming system identifier 220.The primary key 414 is then stored internally within the adapter cryptographic chip 302 and not made accessible from outside the adapter cryptographic chip 302.It has been discovered that the security provisioning system 602 can self-generate and instantiate the master key 620 in the automated assembly system 100, the socket adapters 206, or the combination thereof.\",\n \"The process of instantiating the master key 620 in the automated assembly system 100 or the socket adapters 206, never exposes the master key 620 to the outside of the initializing cryptographic chip 614 by keeping the primary key 414 in hardware so it can never be seen but only can be used cryptographically to authenticate other devices, using latest hardware capabilities in a novel way.\",\n \"It has been discovered that provisioning the device programming system 201 with the primary key 414 via the secure network 403 of FIG.\",\n \"4 improves the level of security of the device programming system 201 of FIG.\",\n \"2 by enabling the authentication of the socket adapters 206.By matching the primary key hash 320 and the adapter hash 321 of FIG.\",\n \"3, the device programming system 201 can insure that the correct ones of the socket adapters 206 are being used during operation.\",\n \"It has been discovered that provisioning the socket adapters 206 with the primary key 414 via the secure network 403 improves the level of security of the device programming system 201 by enabling the authentication of the socket adapters 206.By calculating the adapter hash 321 based on the primary key 414 and the adapter identifier 306, the device programming system 201 can insure that the correct ones of the socket adapters 206 are being used during operation.\",\n \"It has been discovered that provisioning the socket adapters 206 with the primary key 414 encrypted using the programming system identifier 220 and the adapter identifier 302 improves the level of security of the device programming system 201 by enabling the authentication of the socket adapters 206 and keeping the primary key 414 hidden from view.\",\n \"By decrypting the primary key 414 using the programming system identifier 220 and the adapter identifier 306, the device programming system 201 can insure that the correct ones of the socket adapters 206 are being used during operation.\",\n \"Referring now to FIG.\",\n \"8, therein is shown a flow chart for an automated manufacturing system 800 for operating the automated manufacturing system 800 in accordance with an alternative embodiment of the present invention.\",\n \"The automated manufacturing system 800 includes detecting a socket adapter having an adapter identifier and an adapter cryptographic chip in a block 802; calculating a primary key hash based on a primary key in a programming cryptographic chip in a block 804; calculating an adapter hash based on the adapter identifier using the adapter cryptographic chip in a block 806; matching the primary key hash to the adapter hash to update an authentication token with the adapter identifier for authenticating the socket adapter on the device programming system in a block 808; and programming programmable devices in the socket adapter based on the authentication token in a block 810.It has been discovered that the present invention thus has numerous aspects.\",\n \"The present invention valuably supports and services the historical trend of reducing costs, simplifying systems, and increasing performance.\",\n \"These and other valuable aspects of the present invention consequently further the state of the technology to at least the next level.\",\n \"The resulting processes and configurations are straightforward, cost-effective, uncomplicated, highly versatile and effective, can be surprisingly and unobviously implemented by adapting known technologies, and are thus readily suited for efficiently and economically configuring programmable devices fully compatible with conventional manufacturing processes and technologies.\",\n \"While the invention has been described in conjunction with a specific best mode, it is to be understood that many alternatives, modifications, and variations will be apparent to those skilled in the art in light of the aforegoing description.\",\n \"Accordingly, it is intended to embrace all such alternatives, modifications, and variations, which fall within the scope of the included claims.\",\n \"All matters hithertofore set forth herein or shown in the accompanying drawings are to be interpreted in an illustrative and non-limiting sense.\"\n ]\n]"},"source":{"kind":"string","value":"Patent_15871967"}}},{"rowIdx":4493967,"cells":{"text":{"kind":"list like","value":[["Autonomous vehicle having an external shock-absorbing energy dissipation padding","An autonomous on-road vehicle having an outer nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP).","In one embodiment, the SAEDP is mounted, during normal driving, to the front side of the vehicle at eye level of an occupant who sits in a front seat of the vehicle.","A camera is mounted to the vehicle and takes video of the outside environment in front of the occupant.","And a computer generates a representation of the outside environment at eye level for the occupant."],["1.An autonomous on-road vehicle having an outer nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP), comprising: an SAEDP mounted, during normal driving, to the front side of the vehicle at eye level of an occupant who sits in a front seat of the vehicle; a camera mounted to the vehicle and configured to take video of the outside environment in front of the occupant; and a computer configured to generate, based on the video, a representation of the outside environment at eye level for the occupant.","2.The autonomous on-road vehicle of claim 1, wherein the SAEDP is less stiff than a standard automotive glass window and is designed to absorb some of the crashing energy transmitted to a pedestrian during a pedestrian-vehicle collision.","3.The autonomous on-road vehicle of claim 1, wherein the SAEDP comprises a passive material.","4.The autonomous on-road vehicle of claim 3, wherein the SAEDP has thickness greater than at least one of the following thicknesses: 1 cm, 2 cm, 5 cm, 10 cm, 15 cm, and 20 cm.","5.The autonomous on-road vehicle of claim 1, wherein the SAEDP comprises an automotive airbag configured to inflate in order to protect the pedestrian.","6.The autonomous on-road vehicle of claim 5, wherein the airbag has a stowed condition and an inflated condition; the airbag is coupled to an inflator configured to inflate the airbag with gas, and the airbag is located, in the stowed condition, at eye level in front of the occupant; and further comprising an autonomous-driving control system configured to calculate probability of pedestrian-vehicle collision, based on measurements of sensors mounted on the vehicle, and to command the airbag to inflate before the pedestrians head hits the vehicle.","7.The autonomous on-road vehicle of claim 1, wherein the SAEDP comprises a pneumatic pad configured to inflate in order to protect the pedestrian, and further comprising an autonomous-driving control system configured to calculate probability of pedestrian-vehicle collision, based on measurements of sensors mounted on the vehicle, and to command the pneumatic pad to start inflate at least 0.5 second before the crash in order to protect the pedestrian.","8.The autonomous on-road vehicle of claim 7, wherein the pneumatic pad is reusable.","9.The autonomous on-road vehicle of claim 1, wherein the representation is generated from the point of view of the occupant, and further comprising a display configured to present the representation to the occupant.","10.An autonomous on-road vehicle having an outer nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP), comprising: an SAEDP stored above or below a windshield located at eye level in front of an occupant who sits in a front seat of the vehicle; a motor configured to move the SAEDP between a first state, in which the SAEDP does not block the occupant's eye level frontal view to the outside environment, and a second state, in which the SAEDP blocks the occupant's eye level frontal view to the outside environment, multiple times without having to be repaired; and a processor configured to receive an indication that a probability of an imminent pedestrian-vehicle collision reaches a threshold, and to command the motor to move the SAEDP from the first state to the second state.","11.The autonomous on-road vehicle of claim 10, wherein the SAEDP is less stiff than a standard automotive glass window, and in the second state the SAEDP is configured to absorb some of the crashing energy transmitted to a pedestrian during a pedestrian-vehicle collision.","12.The autonomous on-road vehicle of claim 10, wherein the processor is further configured to receive an updated indication that the probability of the imminent pedestrian-vehicle collision does not reach a second threshold, and to command the motor to move the SAEDP to the first state; wherein the second threshold is lower than the threshold, and the processor receives at least one of the indication and the updated indication from an autonomous-driving control system.","13.The autonomous on-road vehicle of claim 10, wherein the motor is configured to move the SAEDP over a sliding mechanism, and the processor is configured to command the motor to start moving the SAEDP to the second state at least 0.2 second, 0.5 second, 1 second, or 2 seconds before the pedestrian-vehicle collision in order to protect the pedestrian.","14.The autonomous on-road vehicle of claim 10, wherein the SAEDP comprises a pneumatic pad configured to inflate in order to protect the pedestrian.","15.The autonomous on-road vehicle of claim 14, wherein the pneumatic pad is reusable, and the processor is configured to command the pneumatic pad to start inflate at least 0.5 second before the pedestrian-vehicle collision.","16.The autonomous on-road vehicle of claim 10, wherein the SAEDP comprises a passive material having thickness greater than at least one of the following thicknesses: 1 cm, 2 cm, 5 cm, 10 cm, 15 cm, and 20 cm.","17.The autonomous on-road vehicle of claim 10, further comprising a camera configured to take video of the outside environment while the SAEDP is in the second state, a computer configured to generate a representation of the outside environment based on the video, and a display configured to present the representation of the outside environment to the occupant while the SAEDP is in the second state.","18.The autonomous on-road vehicle of claim 17, wherein the camera is fixed to the SAEDP, and thus moves with the SAEDP when it is moved between the first and second states.","19.The autonomous on-road vehicle of claim 17, wherein the display is fixed to the SAEDP from the inner side, and thus moves with the SAEDP when it is moved between the first and second states; whereby the occupant can watch the display via the windshield when the SAEDP is in the second state.","20.The autonomous on-road vehicle of claim 17, wherein the display is at least one of the following displays: a display that is physically coupled to the compartment of the autonomous on-road vehicle, and a display comprised in a head-mounted display."],[" BACKGROUND Vehicle-pedestrian collisions claim many casualties.","This is likely to persist even in the age of autonomous vehicles.","In some cases, collisions with pedestrians may be simply impossible to avoid or too dangerous (to the vehicle occupants) to avoid.","Vehicle-pedestrian collisions often involve the pedestrian hitting the stiff windshield, which can lead to severe bodily harm to the pedestrian and maybe also to damage the windshield.","Thus, there is a need for devices that can reduce the danger in vehicle-pedestrian collisions."],[" SUMMARY Some aspects of this disclosure involve an autonomous on-road vehicle that includes an outer nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) mounted to the front side of the vehicle during normal driving, such that the SAEDP is in front of and at eye level of an occupant who sits in a front seat of the vehicle.","Additionally, the vehicle includes a camera that is mounted to the vehicle and is configured to take video of the outside environment in front of the occupant, and a computer configured to generate, based on the video, a representation of the outside environment at eye level for the occupant.","A non-limiting advantage of this vehicle is that it increases the safety of a pedestrian in case of a vehicle-pedestrian collision, without prohibiting the occupant of the vehicle from receiving a frontal view of the outside environment.","Another aspect of this disclosure involves an autonomous on-road vehicle having an outer nontransparent SAEDP.","The SAEDP is stored above or below a windshield located at eye level in front of an occupant who sits in a front seat of the vehicle.","A motor moves the SAEDP between a first state, in which the SAEDP does not block the occupant's eye level frontal view to the outside environment, and a second state, in which the SAEDP blocks the occupant's eye level frontal view to the outside environment, multiple times without having to be repaired.","A processor receives an indication that a probability of an imminent pedestrian-vehicle collision reaches a threshold, and commands the motor to move the SAEDP from the first state to the second state.","A non-limiting advantage of this vehicle is that it increases the safety of a pedestrian in case of a vehicle-pedestrian collision, while still having an uncovered windshield during normal driving."],["CROSS-REFERENCE TO RELATED APPLICATIONS This application is a Continuation-In-Part of U.S. application Ser.","No.","15/335,404, filed Oct. 26, 2016, which claims priority to U.S.","Provisional Patent Application No.","62/246,187, filed on 26 Oct. 2015, and U.S.","Provisional Patent Application No.","62/369,127, filed on 31 Jul.","2016.ACKNOWLEDGMENTS Gil Thieberger would like to thank his holy and beloved teacher, Lama Dvora-hla, for her extraordinary teachings and manifestation of wisdom, love, compassion and morality, and for her endless efforts, support, and skills in guiding him and others on their paths to freedom and ultimate happiness.","Gil would also like to thank his beloved parents for raising him exactly as they did.","BACKGROUND Vehicle-pedestrian collisions claim many casualties.","This is likely to persist even in the age of autonomous vehicles.","In some cases, collisions with pedestrians may be simply impossible to avoid or too dangerous (to the vehicle occupants) to avoid.","Vehicle-pedestrian collisions often involve the pedestrian hitting the stiff windshield, which can lead to severe bodily harm to the pedestrian and maybe also to damage the windshield.","Thus, there is a need for devices that can reduce the danger in vehicle-pedestrian collisions.","SUMMARY Some aspects of this disclosure involve an autonomous on-road vehicle that includes an outer nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) mounted to the front side of the vehicle during normal driving, such that the SAEDP is in front of and at eye level of an occupant who sits in a front seat of the vehicle.","Additionally, the vehicle includes a camera that is mounted to the vehicle and is configured to take video of the outside environment in front of the occupant, and a computer configured to generate, based on the video, a representation of the outside environment at eye level for the occupant.","A non-limiting advantage of this vehicle is that it increases the safety of a pedestrian in case of a vehicle-pedestrian collision, without prohibiting the occupant of the vehicle from receiving a frontal view of the outside environment.","Another aspect of this disclosure involves an autonomous on-road vehicle having an outer nontransparent SAEDP.","The SAEDP is stored above or below a windshield located at eye level in front of an occupant who sits in a front seat of the vehicle.","A motor moves the SAEDP between a first state, in which the SAEDP does not block the occupant's eye level frontal view to the outside environment, and a second state, in which the SAEDP blocks the occupant's eye level frontal view to the outside environment, multiple times without having to be repaired.","A processor receives an indication that a probability of an imminent pedestrian-vehicle collision reaches a threshold, and commands the motor to move the SAEDP from the first state to the second state.","A non-limiting advantage of this vehicle is that it increases the safety of a pedestrian in case of a vehicle-pedestrian collision, while still having an uncovered windshield during normal driving.","BRIEF DESCRIPTION OF THE DRAWINGS The embodiments are herein described by way of example only, with reference to the accompanying drawings.","No attempt is made to show structural details of the embodiments in more detail than is necessary for a fundamental understanding of the embodiments.","In the drawings: FIG.","1 is a schematic illustration of components of a system configured to combine video see-through (VST) with video-unrelated-to-the-VST (VUR); FIG.","2 illustrates an HMD tracking module that measures the position of the HMD relative to the compartment; FIG.","3 illustrates a vehicle in which an occupant wears an HMD; FIG.","4 illustrates an occupant wearing an HMD and viewing large VUR and smaller VST; FIG.","5a illustrates how the VST moves to the upper left when the occupant looks to the bottom right; FIG.","5b illustrates how the VST moves to the bottom right when the occupant looks to the upper left; FIG.","6 illustrates HMD-video that includes both a non-transparent VST and video that shows the hands of the occupant and the interior of the compartment; FIG.","7 illustrates HMD-video that includes both a partially transparent VST and video that shows the hands of the occupant and the interior of the compartment; FIG.","8 illustrates HMD-video that includes a VST and partially transparent video that shows the hands of the occupant and the interior of the compartment; FIG.","9a illustrates HMD-video that includes a VUR in full FOV, a first window comprising compartment-video (CV) and a second smaller window comprising the VST; FIG.","9b illustrates HMD-video that includes VUR in full FOV, a first window comprising the CV and a second partially transparent smaller window comprising the VST; FIG.","10a illustrates HMD-video that includes VUR in full FOV, a first window comprising VST and a second smaller window comprising zoom out of the CV; FIG.","10b illustrates HMD-video that includes VUR and a partially transparent CV; FIG.","11a illustrates a FOV of a vehicle occupant when the occupant wears an HMD that presents HMD-video; FIG.","11b illustrates a FOV of a vehicle occupant when the vehicle occupant does not wear an HMD that presents the video, such as when watching an autostereoscopic display; FIG.","11c illustrates FOV of a 3D camera that is able to capture sharp images from different focal lengths; FIG.","12 is a schematic illustration of components of a system configured to enable an HMD to cooperate with a window light shading module; FIG.","13a illustrates a first mode for a shading module where an occupant sees the outside environment through the optical see-through component; FIG.","13b illustrates a second mode for a shading module where the occupant sees the outside environment through a VST; FIG.","14 illustrates a VST over a curtain; FIG.","15 illustrates a light shading module that is unfurled on the inside of the compartment; FIG.","16 illustrates a light shading module that is unfurled on the outside of the compartment; FIG.","17 is a schematic illustration of components of a video system that may be used to increase awareness of an occupant of a vehicle regarding an imminent SDRS; FIG.","18a illustrates presenting VUR to an occupant when there is no indication that an SDRS event is imminent; FIG.","18b illustrates presenting VST responsive to receiving an indication that an SDRS event is imminent (a pothole); FIG.","18c illustrates presenting VST responsive to receiving an indication that an SDRS event is imminent (a sharp turn); FIG.","19a illustrates presenting VUR and VST when there is no indication that an SDRS event is imminent; FIG.","19b illustrates presenting a larger VST responsive to receiving an indication that an SDRS event is imminent (a road bump); FIG.","19c illustrates presenting a partially transparent VST responsive to receiving an indication that an SDRS event is imminent; FIG.","20a illustrates a smart glass shading module when there is no indication that an SDRS event is imminent; FIG.","20b illustrates the smart glass shading module when there is an indication that an SDRS event is imminent; FIG.","21a and FIG.","21b illustrate vehicles with an SAEDP in their compartment were an occupant uses an HMD to receive a representation of the outside environment; FIG.","22 illustrates a vehicle with an SAEDP in the vehicle's compartment with displays; FIG.","23 illustrates how an SAEDP protects the occupant in a side collision; FIG.","24a and FIG.","24b illustrate a vehicle with a motor configured to move a nontransparent SAEDP to cover a side window; FIG.","25a and FIG.","25b illustrate a vehicle with a motor configured to move a front SAEDP between first and second states; FIG.","26a illustrates an SAEDP mounted to the front of a vehicle at eye level of an occupant of the vehicle; FIG.","26b illustrates an outer SAEDP that includes two air bags; FIG.","27a and FIG.","27b illustrate a motorized external SAEDP that can move between first and second states multiple times; FIG.","28 illustrates a vehicle compartment in which an occupant may lay down; FIG.","29 illustrates a vehicle with a front mirror; FIG.","30a illustrates one example of a configuration of a plurality of beams located in the left side of the vehicle; FIG.","30b illustrates one example of a configuration of a plurality of beams located in the front of the vehicle; and FIG.","31a and FIG.","31b are schematic illustrations of computers able to realize one or more of the embodiments discussed herein.","DETAILED DESCRIPTION The following are definitions of various terms that may be used to describe one or more of the embodiments in this disclosure.","The terms “autonomous on-road vehicle” and “autonomous on-road manned vehicle” refer to cars and motorcycles designed to drive on public roadways utilizing automated driving of level 3 and above according to SAE International standard J3016 “Taxonomy and Definitions for Terms Related to On-Road Motor Vehicle Automated Driving Systems”.","For example, the autonomous on-road vehicle may be a level 3 vehicle, in which within known, limited environments, drivers can safely turn their attention away from driving tasks; the autonomous on-road vehicle may be a level 4 vehicle, in which the automated system can control the vehicle in all but a few environments; and/or the autonomous on-road vehicle may be a level 5 vehicle, in which no human intervention is required and the automatic system can drive to any location where it is legal to drive.","Herein, the terms “autonomous on-road vehicle” and “self-driving on-road vehicle” are equivalent terms that refer to the same.","The term “autonomous on-road vehicle” does not include trains, airplanes, boats, and armored fighting vehicles.","An autonomous on-road vehicle utilizes an autonomous-driving control system to drive the vehicle.","The disclosed embodiments may use any suitable known and/or to be invented autonomous-driving control systems.","The following three publications describe various autonomous-driving control systems that may be utilized with the disclosed embodiments: (i) Paden, Brian, et al.","“A Survey of Motion Planning and Control Techniques for Self-driving Urban Vehicles.” arXiv preprint arXiv:1604.07446 (2016); (ii) Surden, Harry, and Mary-Anne Williams.","“Technological Opacity, Predictability, and Self-Driving Cars.” Predictability, and Self-Driving Cars (Mar.","14, 2016) (2016); and (iii) Gonzalez, David, et al.","“A Review of Motion Planning Techniques for Automated Vehicles.” IEEE Transactions on Intelligent Transportation Systems 17.4 (2016): 1135-1145.Autonomous-driving control systems usually utilize algorithms such as machine learning, pattern recognition, neural network, machine vision, artificial intelligence, and/or probabilistic logic to calculate on the fly the probability of an imminent collision, or to calculate on the fly values that are indicative of the probability of an imminent collision (from which it is possible to estimate the probability of an imminent collision).","The algorithms usually receive as inputs the trajectory of the vehicle, measured locations of at least one nearby vehicle, information about the road, and/or information about environmental conditions.","Calculating the probability of an imminent collision is well known in the art, also for human driven vehicles, such as the anticipatory collision system disclosed in U.S. Pat.","No.","8,041,483 to Breed.","In order to calculate whether a Sudden Decrease in Ride Smoothness (SDRS) event is imminent, the autonomous-driving control system may compare parameters describing the state of the vehicle at time t1 with parameters describing the state of the vehicle at time t2 that is shortly after t1.If the change in one or more of the parameters reaches a threshold (such as deceleration above a certain value, change of height in the road above a certain value, and/or an angular acceleration above a certain value) then it may be determined that an SDRS event is imminent.","An “occupant” of a vehicle, as the term is used herein refers to a person that is in the vehicle when it drives.","The term “occupant” refers to a typical person having a typical shape, such as a 170 cm tall human (herein “cm” refers to centimeters).","An occupant may be a driver, having some responsibilities and/or control regarding the driving of the vehicle (e.g., in a vehicle that is not completely autonomous), or may be a passenger.","When an embodiment refers to “the occupant of the vehicle”, it may refer to one of the occupants of the vehicle.","Stating that a vehicle has an “occupant” should not be interpreted that the vehicle necessarily accommodates only one occupant at a time, unless that is explicitly stated, such as stating that the vehicle is “designed for a single occupant”.","Herein, a “seat” may be any structure designed to hold an occupant travelling in the vehicle (e.g., in a sitting and/or reclining position).","A “front seat” is a seat that positions an occupant it holds no farther from the front of the vehicle than any other occupants of the vehicle are positioned.","Herein, sitting in a seat also refers to sitting on a seat.","Sitting in a seat is to be interpreted in this disclosure as occupying the space corresponding the seat, even if the occupant does so by assuming a posture that does not necessarily correspond to sitting.","For example, in some vehicles the occupant may be reclined or lying down, and in other vehicles the occupant may be more upright, such as when leaning into the seat in a half standing half seating position similar to leaning into a Locus Seat by Focal Upright LLC.","The interchangeable terms “environment outside the vehicle” and “outside environment” refer to the environment outside the vehicle, which includes objects that are not inside the vehicle compartment, such as other vehicles, roads, pedestrians, trees, buildings, mountains, the sky, and outer space.","A sensor “mounted to the vehicle” may be connected to any relevant part of the vehicle, whether inside the vehicle, outside the vehicle, to the front, back, top, bottom, and/or to a side of the vehicle.","A sensor, as used herein, may also refer to a camera.","The term “camera” refers herein to an image-capturing device that takes images of an environment.","For example, the camera may be based on at least one of the following sensors: a CCD sensor, a CMOS sensor, a near infrared (NIR) sensor, an infrared sensor (IR), and a device based on active illumination such as a LiDAR.","The term “video” refers to a series of images that may be provided in a fixed rate, variable rates, a fixed resolution, and/or dynamic resolutions.","The use of a singular “camera” should be interpreted herein as “one or more cameras”.","Thus, when embodiments herein are described as including a camera that captures video and/or images of the outside environment in order to generate a representation of the outside environment, the representation may in fact be generated based on images and/or video taken using multiple cameras.","Various embodiments described herein involve providing an occupant of the vehicle with representation of the outside environment, generated by a computer and/or processor, based on video taken by a camera.","In some embodiments, video from a single camera (e.g., which may be positioned on the exterior of the vehicle at eye level), may be sent to presentation to the occupant by the processor and/or computer following little, if any, processing.","In other embodiments, video from a single camera or multiple cameras is processed in various ways, by the computer and/or processor, in order to generate the representation of the outside environment that is presented to the occupant.","Methods and systems for stitching live video streams from multiple cameras, stitching live video streams with database objects and/or other video sources, transforming a video stream or a stitched video stream from one point of view to another point of view (such as for generating a representation of the outside environment for an occupant at eye level, or for generating a compartment view for a person standing outside the compartment), tracking the position of an HMD relative to a compartment, and presenting rendered images that are perfectly aligned with the outside world—are all known in the art of computer graphics, video stitching, image registration, and real-time 360° imaging systems.","The following publications are just a few examples of reviews and references that describe various ways to perform the video stitching, image registration, tracking, and transformations, which may be utilized by the embodiments disclosed herein: (i) Wang, Xiaogang.","“Intelligent multi-camera video surveillance: A review.” Pattern recognition letters 34.1 (2013): 3-19.","(ii) Szeliski, Richard.","“Image alignment and stitching: A tutorial.” Foundations and Trends® in Computer Graphics and Vision 2.1 (2006): 1-104.","(iii) Tanimoto, Masayuki.","“FTV: Free-viewpoint television.” Signal Processing: Image Communication 27.6 (2012): 555-570.","(iv) Ernst, Johannes M., Hans-Ullrich Doehler, and Sven Schmerwitz.","“A concept for a virtual flight deck shown on an HMD.” SPIE Defense+Security.","International Society for Optics and Photonics, 2016.","(v) Doehler, H-U., Sven Schmerwitz, and Thomas Lueken.","“Visual-conformal display format for helicopter guidance.” SPIE Defense+Security.","International Society for Optics and Photonics, 2014.","(vi) Sanders-Reed, John N., Ken Bernier, and Jeff GUell “Enhanced and synthetic vision system (ESVS) flight demonstration.” SPIE Defense and Security Symposium.","International Society for Optics and Photonics, 2008.And (vii) Bailey, Randall E., Kevin J. Shelton, and J. J. Arthur III.","“Head-worn displays for NextGen.” SPIE Defense, Security, and Sensing.","International Society for Optics and Photonics, 2011.A video that provides “representation of the outside environment” refers to a video that enables the average occupant, who is familiar with the outside environment, to recognize the location of the vehicle in the outside environment from watching the video.","In one example, the average occupant is a healthy 30 years old human who is familiar with the outside environment, and the threshold for recognizing a video as a “representation of the outside environment” is at least 20 correct recognitions of the outside environment out of 30 tests.","Herein, sentences such as “VST that represents a view of the outside environment from the point of view of the occupant”, or “VST representation of the outside environment, which could have been seen from the point of view of the occupant” refer to a video representing at least a portion of the outside environment, with a deviation of less than ±20 degrees from the occupant's point of view of the outside environment, and zoom in the range of 30% to 300% (assuming the occupant's unaided view is at 100% zoom level).","The VST may be generated based on at least one of the following resources: a video of the outside environment that is taken in real-time, a video of the outside environment that was taken in the past and is played/processed according to the trajectory of the vehicle, a database of the outside environment that is utilized for rendering the VST according to the trajectory of the vehicle, and/or a video that is rendered as function of locations of physical objects identified in the outside environment using detection and ranging systems such as RADAR and/or LIDAR.","Moreover, the term “video see-through (VST)” covers both direct representations of the outside environment, such as a video of the outside environment, and/or enriched video of the outside environment, such as captured video and/or rendered video of the outside environment presented together with one or more layers of virtual objects, as long as more than 20% of the average vehicle occupants, who are familiar with the outside environment, would be able to determine their location in the outside environment, while the vehicle travels, without using a map, and with a margin of error below 200 meters.","However, it is noted that showing a map that indicates the location of the vehicle on the driving path (such as from the start to the destination) is not considered herein as equivalent to the VST, unless the map includes all of the following properties: the map shows images of the path, the images of the path capture at least 5 degrees of the occupant's FOV at eye level, and the images of the path reflect the dynamics of the vehicle and change in a similar manner to a video taken by a camera mounted to the vehicle and directed to the outside environment.","Herein, “field of view (FOV) of the occupant to the outside environment” refers to the part of the outside environment that is visible to the occupant of a vehicle at a particular position and orientation in space.","In one example, in order for an occupant-tracking module to calculate the FOV to the outside environment of an occupant sitting in a vehicle compartment, the occupant-tracking module determines the position and orientation of the occupant's head.","In another example, in order for an occupant-tracking module to calculate the FOV of an occupant sitting in a vehicle compartment, the occupant-tracking module utilizes an eye tracker.","It is noted that sentences such as “a three dimensional (3D) video see-through (VST) that represents a view of the outside environment, which could have been seen from the point of view of the occupant had the FOV not been obstructed by at least a portion of the nontransparent element” cover also just one or more portions of the FOV, and are to be interpreted as “a three dimensional (3D) video see-through (VST) that represents a view of at least a portion of the outside environment, which could have been seen from the point of view of the occupant had at least some of the FOV not been obstructed by at least a portion of the nontransparent element”.","The term “display” refers herein to any device that provides a human user with visual images (e.g., text, pictures, and/or video).","The images provided by the display may be two-dimensional or three-dimensional images.","Some non-limiting examples of displays that may be used in embodiments described in this disclosure include: (i) screens and/or video displays of various devices (e.g., televisions, computer monitors, tablets, smartphones, or smartwatches), (ii) headset- or helmet-mounted displays such as augmented-reality systems (e.g., HoloLens), virtual-reality systems (e.g., Oculus rift, HTC Vive, or Samsung GearVR), and mixed-reality systems (e.g., Magic Leap), and (iii) image projection systems that project images on a occupant's retina, such as: Virtual Retinal Displays (VRD) that create images by scanning low power laser light directly onto the retina, or light-field technologies that transmit light rays directly into the eye.","Various embodiments may include a reference to elements located at eye level.","The “eye level” height is determined according to an average adult occupant for whom the vehicle was designed, who sits straight and looks to the horizon.","Sentences in the form of “an element located at eye level of an occupant who sits in a vehicle” refer to the element and not to the occupant.","The occupant is used in such sentences in the context of “eye level”, and thus claims containing such sentences do not require the existence of the occupant in order to construct the claim.","Sentences such as “SAEDP located at eye level”, “stiff element located at eye level”, and “crumple zone located at eye level” refer to elements that are located at eye level, but may also extended to other levels, such as from sternum level to the roof level, from floor level to eye level, and/or from floor level to roof level.","For example, an SAEDP located at an eye level can extend from sternum level to above the occupant's head, such that at least a portion of the SAEDP is located at the eye level.","Herein, “normal driving” refers to typical driving conditions, which persist most of the time the vehicle is in motion.","During normal driving the probability of a collision is below a threshold that when reached typically involves one or more of the following actions: deployment of safety devices that are not usually deployed (e.g., inflating airbags), taking evasive action to avoid a collision, and warning occupants of the vehicle about an imminent event that may cause a Sudden Decrease in Ride Smoothness (SDRS).","A Shock-Absorbing Energy Dissipation Padding (SAEDP) is an element that may be used to cushion impact of a body during a collision or during SDRS events.","Various types of SAEDPs may be used in embodiments described herein, such as passive materials, airbags, and pneumatic pads.","Some examples of passive materials that may be used for the SAEDP in one or more of the disclosed embodiments include one or more of the following materials: CONFOR® foam by Trelleborg Applied Technology, Styrofoam by The Dow Chemical Company, Micro-Lattice Materials and/or Metallic Microlattices (such as by HRL Laboratories in collaboration with researchers at University of California and Caltech), non-Newtonian energy Absorbing materials (such as D3O® by D3O lab, and DEFLEXION™ by Dow Corning®), Sorbothane® by Sorbothane Incorporated, and padding that includes compression cells and/or shock absorbers of the Xenith LLC type (such as described in U.S. Pat.","No.","8,950,735 and US patent application num.","20100186150), and materials that include rubber such as a sponge rubber.","The term “stiff element” refers to a material having stiffness and impact resistance equal or greater than that of glazing materials for use in motor vehicles as defined in the following two standards: (i) “American National Standard for Safety Glazing Materials for Glazing Motor Vehicles and Motor Vehicle Equipment Operating on Land Highways-Safety Standard” ANSI/SAE Z26.1-1996, and (ii) The Society of Automotive Engineers (SAE) Recommended Practice J673, revised April 1993, “Automotive Safety Glasses” (SAE J673, rev.","April 93).","The term “stiff element” in the context of low speed vehicles refers to a material having stiffness and impact resistance equal or greater than that of glazing materials for use in low speed motor vehicles as defined in Federal Motor Vehicle Safety Standard 205—Glazing Materials (FMVSS 205), from 49 CFR Ch.","V (10-1-04 Edition).","The stiff element may be transparent (such as automotive laminated glass, or automotive tempered glass) or nontransparent (such as fiber-reinforced polymer, carbon fiber reinforced polymer, steel, or aluminum).","Herein, a nontransparent element is defined as an element having Visible Light Transmittance (VLT) between 0% and 20%, which does not enable the occupant to recognize what lies on the other side of it.","For example, a thick ground glass usually allows light to pass through it but does not let the occupant recognize the objects on the other side of it, unlike plain tinted glass that usually lets the occupant recognize the objects on the other side of it, even when it features VLT below 10%.","The nontransparent element includes an opaque element having VLT of essentially 0% and includes a translucent element having VLT below 20%.","VLT is defined as the amount of incident visible light that passes through the nontransparent element, where incident light is defined as the light that strikes the nontransparent element.","VLT is also known as Luminous Transmittance of a lens, a light diffuser, or the like, and is defined herein as the ratio of the total transmitted light to the total incident light.","The common clear vehicle windshield has a VLT of approximately 85%, although US Federal Motor Vehicle Safety Standard No.","205 allows the VLT to be as low as 70%.","Sentences such as “video unrelated to the VST (VUR)” mean that an average occupant would not recognize the video as a representation of the outside environment.","In some embodiments, the content of the VUR does not change as function of the position of the occupant's head, which means that the point of view from which the occupant watches the VUR does not change essentially when the occupant's head moves.","Herein, stabilization effects, image focusing, dynamic resolution, color corrections, and insignificant changes to less than 10% of the frame as function of the position of the occupant's head—are still considered as content that does not change as function of the position of the occupant's head.","Examples of such content (common in the year 2016) include cinema movies, broadcast TV shows, standard web browsers, and Microsoft Office 2016 applications (such as Word, Excel and PowerPoint).","Herein, a “crumple zone” refers to a structure designed to slow down inertia and absorb energy from impact during a traffic collision by controlled deformation.","The controlled deformation absorbs some of the impact within the outer parts of the vehicle, rather than being directly transferred to the occupants, while also preventing intrusion into and/or deformation of the compartment.","Crumple zone may be achieved by various configurations, such as one or more of the following exemplary configurations: (i) by controlled weakening of sacrificial outer parts of the vehicle, while strengthening and increasing the stiffness of the inner parts of the vehicle, such as by using more reinforcing beams and/or higher strength steels for the compartment; (ii) by mounting composite fiber honeycomb or carbon fiber honeycomb outside the compartment; (iii) by mounting an energy absorbing foam outside the compartment; and/or (iv) by mounting an impact attenuator that dissipates impact.","In order to enable an occupant of a vehicle to view the outside environment, without needing to look out of a physical window, some aspects of this disclosure involve systems that combine video see-through (VST) with video-unrelated-to-the-VST (VUR).","In one embodiment, a system configured to combine video see-through (VST) with video-unrelated-to-the-VST (VUR) includes a head-mounted display (HMD), a camera, an HMD tracking module and a computer.","The HMD is configured to be worn by an occupant of a compartment of a moving vehicle and to present an HMD-video to the occupant.","The camera, which is mounted to the vehicle, is configured to take video of the outside environment (Vout).","The HMD tracking module is configured to calculate position of the HMD relative to the compartment, based on measurements of a sensor.","The computer is configured to receive a location of a video see-through window (VSTW) in relation to the compartment, and to calculate, based on the position of the HMD relative to the compartment, a window-location for the VSTW on the HMD-video.","Additionally, the computer is further configured to generate, based on the window-location and the Vout, the VST that represents a view of the outside environment from the point of view of the occupant.","The computer is also configured to generate the HMD-video based on combining the VUR with the VST in the window-location.","It is to be noted that the content of the VUR is unrelated to the video taken by the camera.","In one embodiment, a system configured to combine video see-through (VST) with video-unrelated-to-the-VST (VUR) includes at least the following components: a head-mounted display (HMD), such as HMD 15, a camera (e.g., camera 12), an HMD tracking module 27, and a computer 13.FIG.","1 provides a schematic illustration of at least some of the relationships between the components mentioned above.","The HMD 15 is configured to be worn by an occupant of a compartment of a moving vehicle and to present an HMD-video 16 to the occupant.","In one embodiment, the HMD 15 is an augmented-reality (AR) HMD.","In another embodiment, the HMD 15 is a virtual reality (VR) HMD.","Optionally, in this embodiment, the system further comprises a video camera mounted to the VR HMD, and the VST video comprises video of the compartment received from the video camera mounted to the VR HMD.","In yet another embodiment, the HMD 15 is a mixed reality HMD.","The term “Mixed Reality” (MR) as used herein involves a system that is able to combine real world data with virtual data.","Mixed Reality encompasses Augmented Reality and encompasses Virtual Reality that does not immerse its user 100% of the time in the virtual world.","Examples of mixed reality HMDs include, but are not limited to, Microsoft HoloLens HMD and MagicLeap HMD.","The camera 12, which is mounted to the vehicle, is configured to take video of the outside environment (Vout).","Optionally, the data captured by the camera comprises 3D data.","For example, the camera may be based on at least one of the following sensors: a CCD sensor, a CMOS sensor, a near infrared (NIR) sensor, an infrared sensor (IR), and a device based on active illumination such as a LiDAR.","The HMD tracking module 27 is configured to calculate position of the HMD 15 relative to the compartment, based on measurements of a sensor.","In different embodiments, the HMD tracking module 27 may have different configurations.","In one embodiment, the sensor comprises first and second Inertial Measurement Units (IMUs).","In this embodiment, the first IMU is physically coupled to the HMD 15 and is configured to measure a position of the HMD 15, and the second IMU is physically coupled to the compartment and is configured to measure a position of the compartment.","The HMD tracking module 27 is configured to calculate the position of the HMD 15 in relation to the compartment based on the measurements of the first and second IMUs.","In another embodiment, the sensor comprises an Inertial Measurement Unit (IMU) and a location measurement system.","In this embodiment, the IMU is physically coupled to the HMD 15 and is configured to measure an orientation of the HMD 15.The location measurement system is physically coupled to the compartment and is configured to measure a location of the HMD in relation to the compartment.","The HMD tracking module 27 is configured to calculate the position of the HMD 15 in relation to the compartment based on the measurements of the IMU and the location measurement system.","Optionally, the location measurement system measures the location of the HMD 15 in relation to the compartment based on at least one of the following inputs: a video received from a camera that captures the HMD 15, a video received from a stereo vision system, measurements of magnetic fields inside the compartment, wireless triangulation measurements, acoustic positioning measurements, and measurements of an indoor positioning systems.","FIG.","2 illustrates one embodiment in which the HMD tracking module 27 is physically coupled to the compartment and is configured to measure the position of the HMD relative to the compartment.","The HMD tracking module 27 may utilize a passive camera system, an active camera system that captures reflections of a projected grid, and/or a real-time locating systems based on microwaves and/or radio waves.","The computer 13 is configured to receive a location of a video see-through window (VSTW) in relation to the compartment, and to calculate, based on the position of the HMD relative to the compartment, a window-location for the VSTW on the HMD-video.","The computer 13 is also configured to generate, based on the window-location and the Vout, the VST that represents a view of the outside environment from the point of view of the occupant.","Optionally, the VST is rendered as a 3D video content.","Additionally, the computer 13 is further configured to generate the HMD-video 16 based on combining the VUR with the VST in the window-location.","The computer 13 may use various know in the art computer graphics functions and/or libraries to generate the VST, transform the VST to the occupant's point of view, render the 3D video content, and/or combine the VUR with the VST.","In one embodiment, the content of the VUR does not change when the occupant moves the head, and the content of the VUR is unrelated to the video taken by the camera.","Additionally, the content of the VUR is generated based on data that was received more than 2 seconds before the HMD-video 16 is displayed to the occupant.","Some examples of the VUR include a video stream of at least one of the following types of content: a recorded television show, a computer game, an e-mail, and a virtual computer desktop.","FIG.","3 illustrates one embodiment in which the occupant 14 wears an HMD 15.The HMD 15 provides video to the occupant 14 through the display of the HMD 15.The vehicle includes a camera 12 that takes video of the outside environment 11a and processes it in a manner suitable for the location of the occupant.","The processed video is provided to the occupant's display in the HMD 15 as a VSTW and the position of the VSTW is calculated in relation to the compartment of the vehicle and moves with the compartment.","While the vehicle is in motion, the VSTW change its content to represent the outside environment 11a of the vehicle.","Whereas the video-unrelated-to-the-VST doesn't change when the occupant moves his head.","The computer is configured to receive a location of a VSTW in relation to the compartment, and to calculate, based on the position of the occupant's head, a window-location for the VSTW on the video.","FIG.","4 illustrates one embodiment in which the occupant 44 wears HMD 45 and views large VUR 40 and smaller VST 41a.","The VUR 40 does not change when the occupant's head 44 moves.","The VSTW presents video of the street based on video taken by the camera that is mounted to the vehicle.","The location of the video-see-through window in relation to the compartment does not change when the occupant 44 moves his/her head in order to imitate a physical window that does not change its position relative to the compartment when the occupant's head moves.","FIG.","5a illustrates how, in one embodiment, the VST moves to the upper left when the occupant 44 looks to the bottom right.","FIG.","5b illustrates how the VST moves to the bottom right when the occupant 44 looks to the upper left, while the VUR moves with the head.","In both cases, the VUR moves with the head while the location of the VST changes according to the movement of the head relative to the compartment as measured by the HMD tracking module 27.In some embodiments, the content of the VUR may be augmented-reality content, mixed-reality content, and/or virtual-reality content rendered to correspond to the occupant's viewing direction.","In this embodiment, the VUR is unrelated to the video taken by the camera.","In one example, the VUR may include a video description of a virtual world in which the occupant may be playing a game (e.g., represented by an avatar).","Optionally, in this example, most of the features of the virtual world are different from the view of the outside of the vehicle (as seen from the occupant's viewing direction).","For example, the occupant may be driving in a city, while the virtual world displays woods, a meadow, or outer space.","In another example, the VUR may include augmented reality content overlaid above a view of the inside of the compartment.","In addition to the components described above, in some embodiments, the system may include a second camera that is mounted to the HMD and is configured to take video of the compartment (Vcomp).","In this embodiment, the computer is further configured to generate a compartment-video (CV), based on Vcomp and a location of a compartment-video window (CVW) in relation to the HMD-video (e.g., HMD-video 16), and to generate the HMD-video also based on the CV in the CVW, such that the HMD-video combines the VUR with the VST in the window-location and with the CV in the CVW.","There are various ways in which the CVW may be incorporated into the HMD-video.","Some examples of these approaches are illustrated in the following figures.","FIG.","6 illustrates HMD-video that includes both a non-transparent VST 55 in the window-location and a CV 56 that shows the hands of the occupant and the interior of the compartment in the CVW.","FIG.","7 illustrates HMD-video that includes both a partially transparent VST 57 in the window-location and the CV 56 that shows the hands of the occupant and the interior of the compartment in the CVW.","FIG.","8 illustrates HMD-video that includes a VST 58 and partially transparent CV 59.The figure illustrates that the occupant sees the outside environment in full field-of-view (FOV), while on top of it there is a partially transparent image (illustrated as dotted image) of the compartment and the hands of the occupant, in order to help the occupant not to hit things in the compartment.","FIG.","9a illustrates HMD-video that includes a VUR 70 in full FOV, a first window comprising the CV 71 in the CVW and a second smaller window comprising the VST 72 in the window-location.","FIG.","9b illustrates HMD-video that includes VUR 70 in full FOV, a first window comprising the CV 71 in the CVW and a second partially transparent smaller window comprising the VST 73 in the window-location.","FIG.","10a illustrates HMD-video that includes VUR 70 in full FOV, a first window comprising VST 75 in the window-location and a second smaller window comprising zoom out of the CV 76 in the CVW.","Optionally, the cabin view in the zoom out is smaller than in reality, and may enable the occupant to orient in the cabin.","Optionally, the occupant may move the CVW, as illustrated in FIG.","10a where the zoom out of the CV in the CVW is somewhat above its location in reality.","FIG.","10b illustrates HMD-video that includes VUR 70 and a partially transparent CV 72.Here a first occupant sees the VUR in full field-of-view (FOV), and on top of it there is a partially transparent image of the compartment and a second occupant that sits to the left of the first occupant, which may help the first occupant not to hit the second occupant.","There may be various ways in which the system determines the location and/or size of the VSTW.","In one embodiment, the VSTW is pinned to at least one of the following locations: a specific physical location and a location of an object in the compartment, such that the location of the VSTW in relation to the compartment does not change when the occupant moves his/her head with the HMD 15 as part of watching the HMD-video 16 and without commanding the VSTW to move in relation to the compartment.","In another embodiment, the system includes a user interface configured to receive a command from the occupant to move and/or resize the VSTW in relation to the compartment.","In one example, the command is issued through a voice command (e.g., saying “move VST to the bottom”).","In another example, the command may be issued by making a gesture, which is detected by a gesture control module in the compartment and/or on a device of the occupant (e.g., as part of the HMD).","Optionally, in this embodiment, the computer is further configured to: update the window-location based on the command from the occupant, and generate an updated VST based on the updated window-location and the video taken by the camera.","In this embodiment, the VST and the updated VST present different VSTW locations and/or dimensions in relation to the compartment.","Optionally, the HMD is configured not to present any part of the VST to the occupant when the window-location is not in the field of view presented to the occupant through the HMD.","In yet another embodiment, the system may further include a video analyzer configured to identify an Object Of Interest (OOI) in the outside environment.","For example, the OOI of interest may be a certain landmark (e.g., a building), a certain object (e.g., a store or a certain model of automobile), or a person.","In this embodiment, the computer is further configured to receive, from the video analyzer, an indication of the position of the OOI, and to track the OOI by adjusting the window-location according to the movements of the vehicle, such that the OOI is visible via the VST.","Optionally, the HMD is configured not to present any part of the VST to the occupant when the window-location is not in the field of view presented to the occupant through the HMD.","The VST that represents the view of the outside environment from the point of view of the occupant, in some embodiments, does not necessarily match the video taken by the cameras.","In one embodiment, the VST may utilize image enhancement techniques to compensate for outside lighting conditions, to give an occupant an experience similar to looking out through a conventional vehicle window but without the view being distorted by raindrops or dirt on the window, and/or to improve the visual impression of the outside environment e.g.","by showing background images which are different from those retrievable from the outside environment.","Additionally or alternatively, the VST may mimic the outside environment, alter the outside environment, and/or be completely different from what can be seen on the outside environment.","The VST may be focused on providing visual information that makes the travelling more fun.","The vehicle may provide different styles of the outside environment to different occupants in the vehicle, such that a first VST provided to a first occupant may mimic the outside environment, while a second VST provided to a second occupant may alter the outside environment and/or be completely different from the outside environment, optionally for comfort enhancement and/or entertainment.","In some embodiments, the VST is informative, and aids at least some of the occupants to determine the location of the vehicle in the environment.","In one embodiment, at least some of those occupants could not determine their location without the VST.","In one example, less than 20% of average vehicle occupants, who are familiar with the outside environment, are able to determine their real location in the outside environment by watching the VUR, without using a map, with a margin of error that is less than 100 meters, and while the vehicle travels; while more than 20% of the average vehicle occupants, who are familiar with the outside environment, are able to determine their real location in the outside environment by watching the VST, without using a map, and with a margin of error that is less than 100 meters, and while the vehicle travels.","FIG.","11a illustrates a FOV in the context of presented video and terminology used herein.","The vehicle occupant 200 wears an HMD 201 that presents HMD-video (such as HMD-video 16).","The HMD-video may be presented at a single focal plane, or at multiple focal planes, depending on the characteristics of the HMD 201 (when the occupant focuses on a certain focal plane, then his/her point of gaze is said to be on the certain focal plane).","In addition, the presented objects may be two-dimensional (2D) virtual objects and/or three-dimensional (3D) virtual objects that may also be referred to as holographic objects.","Element 204 represents the location of a nontransparent element fixed to the vehicle compartment.","In one example, the HMD 201 is a holographic HMD, such as Microsoft HoloLens, which can present content displayed on a series of focal planes that are separated by some distance.","The virtual objects may be presented before the nontransparent element (e.g., polygons 202, 203), essentially on the nontransparent element 204, and/or beyond the nontransparent element (e.g., polygons 205, 206).","As a result, the occupant's gaze distance may be shorter than the distance to the nontransparent element (e.g., distance to polygons 202, 203), essentially equal to the distance to the nontransparent element 204, and/or longer than the distance to the nontransparent element (e.g., distance to polygons 205, 206).","Polygon 207 represents a portion of the presented video at eye level of the vehicle occupant, which in one example is within ±7 degrees from the horizontal line of sight.","Although the figure illustrates overlapping FOVs of polygons 202, 203, 204, and 205, the HMD may show different objects, capturing different FOVs, at different focal planes.","In one example, the HMD may project an image throughout a portion of, or all of, a display volume.","Further, a single object such as a vehicle could occupy multiple volumes of space.","According to the terminology used herein, the nontransparent element 204 is said to be located on FOV overlapping the FOV of polygons 205 and 203 because polygons 203, 204, 205 share the same FOV.","FOV of polygon 206 is contained in the FOV of polygon 204, and FOV of polygon 207 intersects the FOV of polygon 204.FOV of polygon 203 is before the nontransparent element 204 and therefore may hide the nontransparent element 204 partially or entirely, especially when utilizing a multi-focal plane HMD.","FIG.","11b illustrates a FOV in the context of the presented video, where the vehicle occupant 210 does not wear an HMD that presents the video, such as when watching an autostereoscopic display.","The autostereoscopic display is physically located on plane 214 and the presented video may be presented at a single focal plane, or at multiple focal planes, depending on the characteristics of the autostereoscopic display.","In one example, the autostereoscopic display is a holographic display, such as SeeReal Technologies holographic display, where the presented video may present virtual objects before the focal plane of the autostereoscopic display (e.g., planes 212, 213), essentially on the focal plane of the autostereoscopic display 214, and/or beyond the focal plane of the autostereoscopic display (e.g., planes 215, 216).","As a result, the occupant's gaze distance may be shorter than the distance to the autostereoscopic display (e.g., planes 212, 213), essentially equal to the distance to the autostereoscopic display 214, and/or longer than the distance to the autostereoscopic display (e.g., planes 215, 216).","The term “autostereoscopic” includes technologies such as automultiscopic, glasses-free 3D, glassesless 3D, parallax barrier, integral photography, lenticular arrays, Compressive Light Field Displays, holographic display based on eye tracking, color filter pattern autostereoscopic display, volumetric display that reconstructs light field, integral imaging that uses a fly's-eye lens array, and/or High-Rank 3D (HR3D).","FIG.","11c illustrates FOV of a 3D camera that is able to capture sharp images from different focal lengths.","In some embodiments, the vehicle and/or the HMD utilize at least one Inertial Measurement Unit (IMU), and the system utilizes an Inertial Navigation System (INS) to compensate imperfections in the IMU measurements.","An INS typically has one or more secondary navigation sensors that provide direct measurements of the linear velocity, position and/or orientation of the vehicle.","These secondary navigation sensors could be anything from stereo vision systems, to GPS receivers, to digital magnetic compasses (DMCs) or any other type of sensor that could be used to measure linear velocity, position and/or orientation.","In one example, the information from these secondary navigation sensors is incorporated into the INS using an Extended Kalman Filter (EKF).","The EKF produces corrections that are used to adjust the initial estimations of linear velocity, position and orientation that are calculated from the imperfect IMU measurements.","Adding secondary navigation sensors into an INS can increase its ability to produce accurate estimations of the linear velocity, position and orientation of the vehicle over long periods of time.","In one embodiment, the system utilizes domain specific assumptions in order to reduce drift of an INS used to calculate the HMD spatial position in relation to the compartment.","More specifically, the following methods may be used to reduce or correct drift.","Such methods generally fall in the categories of using sensor fusion and/or domain specific assumptions.","(i) Sensor fusion refers to processes in which signals from two or more types of sensors are used to update and/or maintain the state of a system.","In the case of INS, the state generally includes the orientation, velocity and displacement of the device measured in a global frame of reference.","A sensor fusion algorithm may maintain this state using IMU accelerometer and gyroscope signals together with signals from additional sensors or sensor systems.","There are many techniques to perform sensor fusion, such as Kalman filter and particle filter.","One example of periodically correcting drift is to use position data from a triangulation positioning system relative to the compartment.","Such systems try to combine the drift free nature of positions obtained from the triangulation positioning system with the high sampling frequency of the accelerometers and gyroscopes of the IMU.","Roughly speaking, the accelerometer and gyroscope signals are used to ‘fill in the gaps’ between successive updates from the triangulation positioning system.","Another example of reducing the drift is using a vector magnetometer that measures magnetic field strength in a given direction.","The IMU may contain three orthogonal magnetometers in addition to the orthogonal gyroscopes and accelerometers.","The magnetometers measure the strength and direction of the local magnetic field, allowing the north direction to be found.","(ii) In some embodiments, it is possible to make domain specific assumptions about the movements of the occupant and/or the vehicle.","Such assumptions can be used to minimize drift.","One example in which domain specific assumptions may be exploited is the assumption that when the vehicle accelerates or decelerates significantly, the HMD accelerates or decelerates essentially the same as the vehicle, allowing HMD drift in velocity to be periodically corrected based on a more accurate velocity received from the autonomous-driving control system of the vehicle.","Another example in which domain specific assumptions may be exploited is the assumption that when the vehicle accelerates or decelerates significantly, the HMDs of two occupants travelling in the same vehicle accelerate or decelerate essentially the same, allowing HMD drifts to be periodically corrected based on comparing the readings of the two HMDs.","Still another example in which domain specific assumptions are exploited is the assumption that the possible movement of an HMD of a belted occupant is most of the time limited to a portion of the compartment, allowing HMD drifts to be periodically corrected based on identifying when the HMD exceeds beyond that portion of the compartment.","In one example, it may be desirable to adjust the position of displaying a virtual object in response to relative motion between the vehicle and the HMD so that the virtual object would appear stationary in location.","However, the HMD IMU may indicate that the HMD is moving even when the detected motion is a motion of the vehicle carrying the HMD.","In order to distinguish between motion of the HMD caused by the vehicle and motion of the HMD relative to the vehicle, non-HMD sensor data may be obtained by the HMD from sensor such as an IMU located in the vehicle and/or the GPS system of the vehicle, and the motion of the vehicle may be subtracted from the motion of the HMD in order to obtain a representation of the motion of the HMD relative to the vehicle.","By differentiating movements of the HMD caused by the occupant motion compared to movements caused by the vehicle motion, the rendering of the virtual object may be adjusted for the relative motion between the HMD and the vehicle.","Using the nontransparent element, instead of a transparent glass window that provides the same FOV to the outside environment, may provide various benefits, such as: (i) reduced manufacturing cost of the vehicle compared to a similar vehicle having instead of the nontransparent element a transparent glass window that provides the same FOV to the outside environment as provided by the 3D display device, (ii) reduced weight of the vehicle compared to a similar vehicle having instead of the nontransparent element a transparent glass window that provides the same FOV to the outside environment as provided by the 3D display device, and provides the same safety level, (iii) better aerodynamic shape and lower drag for the vehicle, which results in an improved energy consumption, and (iv) improved privacy for the occupant as a result of not enabling an unauthorized person standing nearby the vehicle to see the occupant directly.","The term “real-depth VST window (VSTW)” is defined herein as an imaging display that shows a 3D image of an outside environment located beyond a wall that interrupts the occupant's unaided view of the outside environment.","The real-depth VSTW has the following characteristics: (i) the 3D image corresponds to a FOV to the outside environment beyond the wall, as would have essentially been seen by the occupant had the wall been removed; (ii) the outside environment is captured by a camera, and the rendering of the 3D image is based on images taken by the camera; and (iii) while looking via the imaging display, the occupant's point of gaze (where one is looking) is most of the time beyond the wall that interrupts the occupant's unaided view of the outside environment.","A possible test to determine whether “(i) the 3D image corresponds to a FOV to the outside environment beyond the wall, as would have essentially been seen by the occupant had the wall been removed” is whether an imaginary user standing beyond the wall, watching both the real-depth VSTW and the outside environment, would recognize that at least 20% of the contours of objects in the 3D image correspond to the contours of the objects seen on the outside environment.","Differences between the colors of the corresponding objects in the 3D image and the outside environment usually do not affect the criterion of the 20% corresponding contours, as long as the color difference does not affect the perception of the type of object.","For example, different skin colors to corresponding people in the 3D image and the outside environment do not violate the criterion of the 20% corresponding contours.","As another example, differences in the weight and/or height of corresponding objects in the 3D image and the outside environment do not violate the criterion of the 20% corresponding contours as long as the imaginary user understands that the objects correspond to the same person.","Sentences such as “from the FOV of the occupant” are to be interpreted as no more than 20 degrees angular deviation from the field of view of the occupant to the outside environment.","Zoom in/out does not affect the FOV as long as the average occupant would still recognize the rendered environment as the 3D VST.","For example, zoom in of up to ×4, which maintains no more than 20 degrees angular deviation from the FOV of the occupant to the outside environment, is still considered “from the FOV of the occupant”.","Reasonable lateral deviation essentially does not affect the FOV as long as the average occupant would still recognize the rendered environment as the 3D VST.","For example, displaying to the occupant the outside environment from the FOV of a camera located on the roof of the occupant's vehicle, is still considered as showing the outside environment from the occupant's FOV.","A possible test to determine whether “(ii) the outside environment is measured by a camera, and the images taken by the camera are used to render the 3D image” is whether the real-depth VSTW would display a different 3D VST when it does not receive the images taken by the camera.","For example, assuming the camera is a 3D video camera, and the 3D image is a manipulation of the images taken by the 3D video camera; then, when the real-depth VSTW does not receive the images, it cannot show the changes that are taking place in the outside environment.","As another example, assuming the 3D image is mainly rendered from cached data stored in a database, and the camera is used to provide the setup of objects that behave in an unknown way, such as trajectories of nearby vehicles on the road, or a gesture of a person walking beyond the wall; then, when the output of the camera is used to render the 3D image, the real-depth VSTW would represent the unknown trajectory of the nearby vehicles or the unknown gesture of the person, while when the output of the camera is not used to render the 3D image, the real-depth VSTW would not represent the unknown trajectory of the nearby vehicles or the unknown gesture of the person merely because the renderer does not have that data.","A possible test to determine whether “(iii) the occupant's point of gaze (where one is looking) is most of the time beyond the wall that interrupts the occupant's unaided view of the outside environment” includes the following steps: (a) use eye tracker to determine the point of gaze on a representative scenario, (b) measure the distance to the wall, and (c) determine whether the average gaze distance is longer than the distance to the wall.","Some aspects of this disclosure involve a system that utilizes window shading of a vehicle window in order to improve the quality of video viewed by an occupant of the vehicle who wears a head-mounted display (HMD).","In one embodiment, an autonomous on-road vehicle includes a system configured to enable an HMD to cooperate with a window light shading module.","This embodiment involves a light shading module, a camera, a processor, and the HMD.","The light shading module is integrated with a vehicle window and is configured to be in at least one of first and second states.","In the first state the Visible Light Transmittance (VLT) of the vehicle window is above 10% of ambient light entering through the window, in the second state the VLT of the vehicle window is below 50% of ambient light entering through the window, and the VLT of the vehicle window in the first state is higher than the VLT of the vehicle window in the second state.","The camera is fixed to the vehicle and configured to take video of the outside environment.","The processor is configured to generate, based on the video, a video see-through (VST) that represents the outside environment from a point of view of an occupant looking to the outside environment through at least a portion of the vehicle window.","The HMD comprises an optical see-through component and a display component; the HMD is configured to operate according to a first mode of operation when the occupant looks at the direction of the vehicle window and the light shading module is in the first state, and to operate according to a second mode of operation when the occupant looks at the direction of the vehicle window and the light shading module is in the second state.","Wherein the total intensity of the VST light, emitted by the display component and reaching the occupant's eyes, is higher in the second mode than in the first mode.","In one embodiment, a system configured to enable a head-mounted display (HMD) to cooperate with a window light shading module of an autonomous on-road vehicle includes at least the following elements: the HMD 62, a light shading module 61, a camera (such as camera 12), and a processor 18.FIG.","12 is a schematic illustration of at least some of the relationships between the system elements mentioned above.","The light shading module 61 is integrated with a vehicle window and is configured to be in at least one of first and second states.","Optionally, the light shading module 61 covers more than half of the front windshield in the second state.","In one embodiment, in the first state, the Visible Light Transmittance (VLT) of the vehicle window is above 10% of ambient light entering through the window, and in the second state, the VLT of the vehicle window is below 50% of ambient light entering through the window.","Additionally, the VLT of the vehicle window in the first state is higher than the VLT of the vehicle window in the second state.","In another embodiment, in the first state the VLT of the vehicle window is above 70% of ambient light entering through the window, and in the second state, the VLT of the vehicle window is below 30% of ambient light entering through the window.","Herein, “ambient light” in the context of a vehicle refers to visible light that is not controlled by the vehicle, such as light arriving from: the sun, lights of other vehicles, street/road lighting, and various reflections from elements such as windows.","In some embodiments, utilizing the light shading module 61 may improve the quality of images viewed via the HMD 62 when the light shading module 61 is in the second state.","Optionally, the perceived contrast of the optical see-through component is better when the light shading module is in the second state compared to when the light shading module 61 is in the first state.","Various types of light shading modules may be utilized in embodiments described herein.","In one embodiment, the light shading module 61 is a movable physical element configured to reduce the intensity of the ambient light entering into the vehicle compartment through the vehicle window.","Optionally, the light shading module is unfurled on the inside of the compartment in order to block at least 50% of the ambient light intensity.","Optionally, the light shading module is unfurled on the outside of the compartment in order to block at least 50% of the ambient light intensity.","FIG.","13a illustrates a first mode where the occupant sees the outside environment through the optical see-through component.","This figure illustrates the view that the occupant sees when looking outside through the window.","FIG.","13b illustrates a second mode where the occupant sees the outside environment through the VST.","In this example, the outside environment is a bit different, and there is also a virtual Superman floating near the tree.","In another embodiment, the light shading module 61 may be a curtain.","FIG.","14 illustrates a VST over a curtain.","FIG.","15 illustrates a light shading module that is unfurled on the inside of the compartment.","FIG.","16 illustrates a light shading module that is unfurled on the outside of the compartment.","And in yet another embodiment, the vehicle window is made of a material that is able to serve as the light shading module 61 by changing its transparency properties.","The camera is fixed to the vehicle, and configured to take video of the outside environment.","For example, the camera may be based on at least one of the following sensors: a CCD sensor, a CMOS sensor, a near infrared (NIR) sensor, an infrared sensor (IR), and a device based on active illumination such as a LiDAR.","The processor is configured to generate, based on the video, a video see-through (VST 19) that represents the outside environment from a point of view of an occupant looking to the outside environment through at least a portion of the vehicle window.","Optionally, the processor is further configured not to generate the VST 19 when the HMD 62 operates in the first mode.","The HMD 62 comprises an optical see-through component and a display component.","Optionally, the HMD 62 is configured to operate according to a first mode of operation when the occupant looks at the direction of the vehicle window and the light shading module 61 is in the first state, and to operate according to a second mode of operation when the occupant looks at the direction of the vehicle window and the light shading module 61 is in the second state.","The total intensity of the VST light, emitted by the display component and reaching the occupant's eyes, is higher in the second mode than in the first mode.","In one embodiment, in the first mode, intensity of light that reaches the occupant's eyes via the optical see-through component is higher than intensity of light from the VST that is emitted by the display component and reaches the occupant's eyes.","And in the second mode, the intensity of light from the environment that reaches the occupant's eyes via the optical see-through component is lower than the intensity of light from the VST that is emitted by the display component and reaches the occupant's eyes.","In one example, the total intensity of VST light, emitted by the display component and reaching the occupant's eyes, is at least 50% higher in the second mode than in the first mode.","In some embodiments, the display component may be based on a digital display that produces the virtual image (such as in Oculus rift), direct retina illumination (such as in Magic Leap), or other methods that are capable of producing the virtual image.","In one embodiment, the system described above optionally includes an occupant tracking module configured to calculate the point of view of the occupant based on measurements of a sensor.","Optionally, the occupant tracking module is the HMD tracking module 27.Optionally, in this embodiment, the processor is further configured to render the VST based on data received from the occupant tracking module.","Optionally, the display is a three dimensional (3D) display configured to show the occupant the VST, such that point of gaze of the occupant, while looking via the 3D display device, is most of the time beyond the location of the light shading module 61.In some embodiments, an occupant of a vehicle may have the opportunity to view video see-through (VST), which is video generated based on video of the environment outside the vehicle.","VST can often replace the need to look out of a window (if the vehicle has windows).","Some examples of scenarios in which VST may be available in a vehicle include a windowless vehicle, a vehicle with shaded windows having VLT below 30%, and/or when the occupant wears a VR headset.","While traveling in such a vehicle, the occupant may benefit from gaining a view to the outside environment when an unexpected driving event occurs.","By being made aware of the event, the occupant is less likely to be surprised, disturbed, and/or distressed by the event.","While traveling in a vehicle, an occupant of the vehicle may not always be aware of the environment outside and/or of what actions the vehicle is about to take (e.g., breaking, turning, or hitting a speedbump).","Thus, if such an event occurs without the occupant being aware that it is about to happen, this may cause the occupant to be surprised, disturbed, distressed, and even physically thrown off balance (in a case where the event involves a significant change in the balance of the physical forces on the occupant).","This type of event is typically referred to herein as a Sudden Decrease in Ride Smoothness (SDRS) event.","Some examples of SDRS events include at least one of the following events: hitting a speed bump, driving over a pothole, climbing on the curb, making a sharp turn, a hard breaking, an unusual acceleration (e.g., 0-100 km/h in less than 6 seconds), and starting to drive after a full stop.","In some embodiments, an SDRS event takes place at least 2 minutes after starting to travel and it is not directly related to the act of the starting to travel.","Additionally, the SDRS event takes place at least 2 minutes before arriving to the destination and is not directly related to the act of arriving at the destination.","In one example, a sentence such as “an SDRS event is imminent” refers to an SDRS event that is: (i) related to traveling in the vehicle, and (ii) expected to happen in less than 30 seconds, less than 20 seconds, less than 10 seconds, or less than 5 seconds.","In another example, a sentence such as “an SDRS event is imminent” may refer to an event that starts at that instant, or is about to start within less than one second.","The following is a description of an embodiment of a video system that may be used to increase awareness of an occupant of a vehicle regarding an imminent SDRS.","In one embodiment, a video system for an autonomous on-road vehicle includes at least autonomous-driving control system 65, a camera (such as camera 12), a processor (such as processor 18), and video module 66.FIG.","17 is a schematic illustration of at least some of the relationships between the system elements mentioned above.","The autonomous-driving control system 65 is configured to generate, based on trajectory of the vehicle and information about the road, an indication indicative of whether a Sudden Decrease in Ride Smoothness (SDRS) event is imminent.","Optionally, the autonomous-driving control system 65 receives at least some of the information about the road from at least one of the following sources: sensors mounted to the vehicle, sensors mounted to nearby vehicles, an autonomous-driving control system 65 used to drive a nearby vehicle, and a database comprising descriptions of obstacles in the road that are expected to cause intense movement of the vehicle.","In one example, the database comprising the descriptions of the obstacles includes one or more of the following types of data: locations of speed bumps, locations of potholes, locations of stop signs, and locations of sharp turns in the road.","In one embodiment, the autonomous-driving control system 65 is configured to generate the indication indicative of whether an SDRS event is imminent based on at least one of the following configurations: (i) the autonomous-driving control system 65 receives images of the road from a camera, and calculates the indication based on the vehicle trajectory and image analysis of the images, (ii) the autonomous-driving control system 65 receives from a radar reflections of electromagnetic waves from the road, and calculates the indication based on the vehicle trajectory and signal processing of the reflections, and (iii) the autonomous-driving control system 65 receives a notification from a detailed road map, and calculates the indication based on the vehicle trajectory and the notification.","The camera, which is mounted to the vehicle, is configured to take video of the environment outside the vehicle.","Optionally, the data captured by the camera comprises 3D data.","The processor is configured to generate a video see-through (VST) based on the video taken by the camera.","The video module 66 is configured to select a first mode of presentation, in which a video-unrelated-to-the-VST (VUR) is presented on the foveal vision region of the occupant, at eye level, responsive to the indication not indicating that an SDRS event is imminent.","The video module 66 is further configured to select a second mode of presentation, in which the VST is presented on the foveal vision region of the occupant, at eye level, responsive to the indication indicating that an SDRS event is imminent.","Optionally, the VST captures more than 50% of the foveal vision region of the occupant in the second mode of presentation.","In some embodiments, presenting video on the foveal vision region comprises presenting images with at least 50% transparency.","Herein, “foveal vision” refers to an angle of about 5° of the sharpest field of vision.","In one embodiment, in the first mode of presentation, the VUR is presented on the foveal vision region of the occupant with opacity A, and the VST is presented on the foveal vision region of the occupant with opacity B, where A>B>0.Optionally, a normalized opacity parameter takes a value from 0.0 to 1.0, and the lower the value the more transparent the video is.","In this embodiment, in the second mode of presentation, the VUR is presented on the foveal vision region of the occupant with opacity A′, and the VST is presented on the foveal vision region of the occupant with opacity B′, where B′>B and B′>A′.","In optional embodiments, one or more of the following values may be true: A′>0, B=0, and A′=0.Herein, “partially transparent” refers to opacity below one and above zero.","Having the VST presented when an SDRS event is imminent can make the occupant be aware and prepared for the SDRS event.","Thus, the occupant is less likely to be startled, distressed, and/or physically thrown off balance by the SDRS event.","In one example, the SDRS event involves hitting a speedbump, while the occupant views a movie.","About 5 seconds prior to hitting the speedbump, a partially transparent window displaying VST in which the speedbump is highlighted (e.g., flashing red) is presented on the foveal vision region of the occupant for a couple seconds (e.g., by being presented in the center of the movie).","This way upon hitting the speedbump, the occupant is not startled by the event.","In another example, the autonomous-driving control system 65 determines that a “hard breaking” is required, e.g., in order to avoid collision with a vehicle ahead that slowed unexpectedly.","In this example, the occupant may be working on a virtual desktop, and within 100 milliseconds of when the determination is made that the vehicle is about to rapidly deaccelerate (a “hard breaking”), the VST depicting the rear of the vehicle ahead is displayed in the center of the virtual desktop.","This way the occupant is immediately made aware of why the vehicle is breaking and this notification may prompt the occupant to seek a more appropriate posture for the breaking.","Some illustrations of utilization of the different modes of operation are given in the following figures.","FIG.","18a illustrates presenting VUR responsive to not receiving from the autonomous-driving control system 65 an indication that an SDRS event is imminent.","This figure has two parts, the left part shows the vehicle driving over a clean road, and the right part shows the VUR.","FIG.","18b illustrates presenting VST responsive to receiving from the autonomous-driving control system 65 an indication that an SDRS event is imminent.","The figure has two parts, the left part shows the vehicle about to drive over a pothole, and the right part shows a small window showing the pothole over the VUR (optionally to warn the occupant).","FIG.","18c illustrates presenting VST responsive to receiving from the autonomous-driving control system 65 an indication that an SDRS event is imminent.","The figure has two parts, the left part shows the vehicle about to enter a sharp turn, and on the right part shows a small window showing the sharp turn over the VUR (optionally to warn the occupant).","Traditional vehicles typically have a front windshield that offers occupants of the vehicle a frontal view of the outside environment.","However, in some embodiments, this frontal view may be provided using the VST.","For example, in one embodiment, the vehicle includes a nontransparent element, which is coupled to the vehicle, and obstructs at least 30 degrees out of the frontal horizontal unaided FOV to the outside environment of an occupant at eye level.","In one example of a standard vehicle, such as Toyota Camry model 2015, the frontal horizontal unaided FOV extends from the left door through the windshield to the right door.","The use of the nontransparent element improves the safety of the occupant during a collision compared to a similar vehicle having the same total weight and comprising a transparent glass window instead of the nontransparent element.","The nontransparent element may be coupled to the vehicle in various configurations, in embodiments described herein.","In one embodiment, the nontransparent element is fixed to the vehicle at an angle, relative to the occupant, that is covered by the field of view of the VST, and the nontransparent element features visible light transmittance (VLT) below 10% of ambient light.","Various types of displays may be utilized to present the occupant with video (e.g., the VST and/or the VUR).","In one embodiment, the video is presented to the occupant on a screen coupled to the vehicle compartment.","In one example, the screen coupled to the vehicle compartment utilizes parallax barrier technology.","A parallax barrier is a device located in front of an image source, such as a liquid crystal display, to allow it to show a stereoscopic image or multiscopic image without the need for the viewer to wear 3D glasses.","The parallax barrier includes a layer of material with a series of precision slits, allowing each eye to see a different set of pixels, thus creating a sense of depth through parallax.","In another embodiment, the occupant wears a head-mounted display (HMD), and the HMD is used to present the video to the occupant.","Optionally, the HMD is a VR headset, and as a result of presenting the VST, the occupant does not need to remove the VR headset in order to see the cause of the SDRS event.","In some embodiments, the video module 66 may be selective regarding indications of which SRDS events may prompt it to operate in the second mode of operation.","For example, if the occupant is engaged in a game, the video module 66 may refrain from presenting the VST in the foveal vision region if the vehicle is about to make a sharp turn.","However, it may optionally still present the VST in the foveal vision region if the SDRS event involves something that may be more forcefully felt by the occupant, such as extreme evasive maneuvering performed to avoid a collision.","In some embodiments, the video module 66 may determine whether to show a VST responsive to an SRDS event (in the second mode of operation) based on the level of concentration of the occupant.","For example, if the occupant is deeply engaged in a certain activity (e.g., in work or playing a game) above a threshold, the video module 66 may refrain from operating in the second mode for certain SDRS events that would cause the video module 66 to operate in the second mode were the occupant engaged in the certain activity below the threshold.","In one example, the engagement level may be based on the occupant's level of concentration, as measured by a wearable sensor (such as an EEG headset or a smartwatch) or a sensor fixed to the compartment (such as an eye tracker, a thermal camera, or a movement sensor embedded in the seat).","Presenting an occupant of a vehicle with video see-through (VST) of the outside environment from a point of view of the occupant can help the occupant be prepared for various events that may be considered to cause a Sudden Decrease in Ride Smoothness (SDRS events).","Some examples of SDRS events include the following events: hitting a speed bump, driving over a pothole, climbing on the curb, making a sharp turn, a hard breaking, an unusual acceleration (e.g., 0-100 km/h in less than 6 seconds), and starting to drive after a full stop.","In order for the occupant to become aware of an imminent SDRS event, the VST needs to be presented in an attention-grabbing way.","For example, when an SDRS event is imminent, the VST that describes the environment is brought to the center of the occupant's attention by displaying it at eye level and/or increasing the size of the VST (compared to other times when an SDRS event is not imminent).","The following is a description of an embodiment of a video system that may be used to increase awareness of an occupant of a vehicle regarding an imminent SDRS by making the VST more prominent for an imminent SDRS.","In one embodiment, a video system for an autonomous on-road vehicle includes at least the autonomous-driving control system 65, a camera, and a processor.","In this embodiment, the occupant is engaged, at least part of the time, in entertainment- or work-related activities, which involve presentation of video-unrelated-to-the-VST (VUR) to the occupant, for example, on a screen coupled to the compartment of the vehicle or a HMD worn by the occupant.","Some examples of such content (common in the year 2016) include cinema movies, broadcast TV shows, standard web browsers, and Microsoft Office 2016 applications (such as Word, Excel and PowerPoint).","The camera, which is mounted to the vehicle, is configured to take video of the environment outside the vehicle.","The processor is configured to generate, based on the video taken by the camera, a video see-through (VST) of outside environment from a point of view of an occupant of the vehicle.","Optionally, the occupant is in a front seat of the vehicle (such that no other occupant in the vehicle is positioned ahead of the occupant).","In some embodiments, the processor is configured to present video, which may include VUR and/or VST, to the occupant using different presentation modes, depending on whether an SDRS event is imminent.","For example, the video may be presented according to first or second modes, depending on whether an SDRS event is imminent.","Optionally, the VST captures in the video according to the first mode a diagonal FOV of at least 3°, 5°, or 10° of the occupant's FOV.","Optionally, the VST is not presented in the foveal vision region of the occupant in the video according to the first mode, while the VST is presented in the foveal vision region of the occupant in the video according to the second mode.","In one embodiment, responsive to an indication that is not indicative of an imminent SDRS event (generated by the autonomous-driving control system 65), the processor is configured to provide the occupant video according to the first mode.","In the video according to the first mode, the occupant is presented with video that comprises a video-unrelated-to-the-VST (VUR) at eye level in the direction of forward traveling.","Additionally, the video may comprise a video see-through (VST) of outside environment that is not presented at eye level in the direction of forward traveling.","Receiving an indication indicative that an SDRS event is imminent may change the way video is presented to the occupant.","Optionally, this change is made without receiving a command to do so from the occupant.","In one embodiment, responsive to the indication indicating that an SDRS event is imminent, the processor is configured to provide video to the occupant video according to the second mode.","In the video according to the second mode, the occupant is presented with video that comprises the VST, presented at eye level in the direction of forward traveling.","Optionally, if the video according to the first mode includes VST, then the size of the VST window in the video according to the second mode is larger by at least 25% relative to the size of the VST window in the video according to the first mode.","Optionally, the video according to the second mode includes presenting the VUR in the background (e.g., the VST is overlaid above the VUR).","Optionally, while providing the video according to the second mode, responsive to an updated indication that does not indicate that an SDRS event is imminent, the processor is further configured to switch back to provide the video according to the first mode to the occupant.","The following figures illustrate various ways in which the videos according to the first and second modes may be utilized.","FIG.","19a illustrates presenting a VUR, which is a movie showing a person skiing, responsive to not receiving from the autonomous-driving control system 65 an indication that an SDRS event is imminent.","This figure has two parts, the left part shows the vehicle driving over a clean road, and the right part shows the VUR with a small VST on the right.","FIG.","19b illustrates presenting a VST responsive to receiving from the autonomous-driving control system 65 an indication that an SDRS event is imminent.","This figure has two parts, the left part shows the vehicle about to drive over a speed bump, and the right part shows the VUR but now with a big VST on the right.","In this example, the big VST captures about half of the VUR and shows the speed bump.","FIG.","19c illustrates presenting a partially transparent VST responsive to receiving from the autonomous-driving control system 65 an indication that an SDRS event is imminent.","Here, the big VST (that captures about half of the VUR and shows the speed bump) is presented as partially transparent layer over the VUR in order to show the occupant both the VUR and the VST.","In one embodiment, presenting to the occupant video according to the second mode involves presenting the VUR behind the VST, and the size and location of the VUR in the video according to the second mode is essentially the same as the size and location of the VUR in the video according to the first mode.","Optionally, this means that there is a difference of less than 10% in the size and location of the VURs in the videos according to the first and second modes.","In another embodiment, the VUR is presented in a diagonal FOV of at least 10 degrees, and is not based on the video taken by the camera.","In some embodiments, the VUR may be unrelated to the purpose of the traveling in the vehicle.","For example, the VUR may include videos related to the following activities: watching cinema movies, watching TV shows, checking personal emails, playing entertainment games, and surfing in social networks.","In some embodiments, the occupant's field of view (FOV) to the outside environment is obstructed by a nontransparent element, and the VST represents at least a portion of the obstructed FOV.","Optionally, the occupant uses a VR headset and the obstruction is due to a nontransparent element belonging to the VR headset.","Additionally or alternatively, the obstruction may be due to the vehicle's compartment; in this case the nontransparent element may be an SAEDP, a safety beam, and/or a crumple zone at eye level, which obstruct at least 30 degrees out of the frontal horizontal unaided FOV to the outside environment of the occupant at eye level.","When traveling in a vehicle, an occupant of the vehicle may not always be viewing the outside environment.","For example, the occupant may be engaged in work- or entertainment-related activities.","Additionally, in some vehicles, the occupant may not have a good view of the outside environment most of the time, or even all of the time.","For example, the vehicle may have very few (or no) windows, or the vehicle may have a shading mechanism that reduces the light from the outside.","However, there are times when the occupant should be made aware of the outside environment, even though the occupant may not be actively driving the vehicle.","For example, the occupant may be made aware of the outside environment in order to make the occupant prepared for an event that causes a Sudden Decrease in Ride Smoothness (an SDRS event).","Some examples of SDRS events include the following events: hitting a speed bump, driving over a pothole, climbing on the curb, making a sharp turn, a hard breaking, an unusual acceleration (e.g., 0-100 km/h in less than 6 seconds), and starting to drive after a full stop.","In order for the occupant to become aware of an imminent SDRS event, in some embodiments that involve a vehicle that has a shading module that controls how much ambient light is let in, when an SDRS event is imminent the vehicle may increase the amount of light that enters via a window.","This additional light can give an occupant a better view of the outside environment, which can make the occupant aware and better prepared for the SDRS.","The following is a description of an embodiment of a system that may be used to increase awareness of an occupant of a vehicle regarding an imminent SDRS by enabling more ambient light to enter a vehicle via a window.","In one embodiment, a shading system for a window of an autonomous on-road vehicle includes at least the autonomous-driving control system 65, a shading module, and a processor.","FIG.","20a illustrates a smart glass shading module that operates according to an indication that an SDRS event is not imminent.","This figure has two parts, the left part shows the vehicle driving over a clean road, and the right part shows that the smart glass window blocks most of the ambient light (illustrated in the figure by the tree outside that is invisible to the occupant).","FIG.","20b illustrates the smart glass shading module that operates according to an indication that an SDRS event is imminent.","This figure has two parts, the left part shows the vehicle about to drive over a pothole, and the right part shows that the smart glass window does not block the ambient light (illustrated in the figure by the tree outside that is visible to the occupant).","The shading module is configured to control the amount of ambient light that enters the vehicle via the window.","Optionally, the window is a front-facing window (e.g., a windshield).","Optionally, the window is a side-facing window.","There are various types of shading modules that may be utilized in different embodiments.","In one embodiment, the shading module comprises a curtain.","Optionally, the curtain covers most of the area of the window.","Optionally, the curtain may open and close with the aid of an electromechanical device, such as a motor, based on commands issued by the processor.","In another embodiment, the shading module is a movable physical element configured to reduce the intensity of the ambient light entering through the vehicle window into the vehicle compartment.","For example, the shading module may include various forms of blinds, a shutter, or a sliding element.","Optionally, the shading module may be unfurled on the inside of the vehicle compartment in order to block more than 70% of the ambient light intensity.","Optionally, the shading module may be unfurled on the outside of the vehicle compartment in order to block more than 70% of the ambient light intensity.","In yet another embodiment, the shading module comprises a smart glass able to change its light transmission level.","Optionally, the smart glass is a vehicle window smart glass that comprises suspended particle devices (SPDs) film.","Smart glass window may also be known as a switchable glass, a smart window, and/or a switchable window.","Smart glass is glass or glazing whose light transmission properties are altered when voltage, current, light or heat is applied.","Examples of electrically switchable smart glass include: suspended particle devices (SPDs), electrochromic devices, transition-metal hydride electrochromics devices, modified porous nano-crystalline films, polymer dispersed liquid crystal devices, micro-blinds, and thin coating of nanocrystals embedded in glass.","Examples of non-electrical smart glass include: mechanical smart windows, Vistamatic®, and Sunvalve.","The processor is configured to command the shading module to operate in different modes based on indications generated by the autonomous-driving control system 65.In some embodiments, the processor is configured to command the shading module to operate in different modes that allow different amounts of the ambient light to enter the vehicle via the window, depending on whether an SDRS event is imminent.","For example, shading module may operate in first or second modes, depending on whether an SDRS event is imminent.","Optionally, in the first mode the shading module blocks more of the ambient light entering through the vehicle window than in the second mode.","Optionally, the increased ambient light in the second mode can help make the occupant more aware of the outside environment, which can enable the occupant to prepare for the SDRS event.","In one embodiment, responsive to an indication that no SDRS event is imminent, the processor is configured to command a shading module to operate in a first mode in which the shading module blocks more than 30% of ambient light entering through a window of the vehicle.","Receiving an indication indicative that an SDRS event is imminent may change the amount of ambient light that enters the vehicle via the window.","Optionally, this change is made without receiving a command to do so from the occupant.","In one embodiment, responsive to an indication that an SDRS event is imminent, the processor is configured to command the shading module to operate in the second mode in which the shading module blocks less than 90% of the ambient light entering through the vehicle window.","Some aspects of this disclosure include a system that can show an occupant of a vehicle and Object Of Interest (OOI) in the outside environment, which the occupant would otherwise miss (e.g., due to being engaged in work- or entertainment-related activities and/or having no direct view of the outside environment).","In one embodiment, a system configured to identify an Object Of Interest (OOI) in the outside environment, and to present to an occupant of an autonomous on-road vehicle a video see-through (VST) that comprises the OOI, includes at least a camera (such as camera 12), a processor (such as processor 18), and a video module (such as video module 66).","Different types of things may be considered an OOI in different embodiments.","In one embodiment, the OOI is selected from a set comprising: types of vehicles, types of scenery, and types of people.","Optionally, the system may include a user interface configured to present a menu that enables the occupant to select the types of OOI, which when identified, will be presented in the second mode of presentation.","In one example, an OOI may be any type of high-end vehicle (e.g., a Porsche).","In another example, an OOI may include an ocean view.","The camera, which is mounted to the vehicle, is configured to take video of the environment outside the vehicle.","Optionally, the data captured by the camera comprises 3D data.","The processor is configured to generate, based on the video taken by the camera, a video see-through (VST) of outside environment from a point of view of an occupant of the vehicle.","Optionally, the occupant is in a front seat of the vehicle (such that no other occupant in the vehicle is positioned ahead of the occupant).","The video module is configured to present, to the occupant, video that captures diagonal field of view (FOV) of at least 10 degrees, at eye level.","Optionally, the video module is further configured to select a mode of operation based on whether an indication is received that is indicative of whether video taken by the camera include the OOI.","Optionally, changing a mode of operation is done without an expressed command at that time by the occupant.","In one embodiment, when not receiving an indication that the images includes the OOI, the video module is configured to select a first mode of presentation, in which a video-unrelated-to-the-VST (VUR) is presented on the foveal vision region of the occupant.","And responsive to receiving the indication that the images include the OOI, the video module is further configured to select a second mode of presentation, in which the VST is presented on the foveal vision region of the occupant.","There are various ways in which an indication of the OOI may be generated in different embodiments.","In one embodiment, the system includes an image processing module configured to identify the OOI in the VST and to generate the indication.","Various image processing techniques and/or image identification methods known in the art may be utilized by the image processing module for this task.","In another embodiment, the system may include the autonomous-driving control system 65 configured to utilize a positioning system, such as GPS coordinates, to identify that the vehicle reached the OOI and to generate the indication.","Optionally, the occupant may define which places may be OOIs and/or what types of locations are to be considered OOIs (e.g., historical monuments, nice scenery, etc.).","In still another embodiment, the system may include a crowd-based module configured to identify the OOI based on feedback received from many different occupants who watched VSTs comprising the OOI.","Optionally, this feedback may be derived based on indications of how other occupants felt about the VST (when it depicted certain content corresponding to OOIs).","For example, points of interest may be determined according to affective crowd data, determine based on how other occupants felt about what they saw, and optionally find places where the crowd affective response was positive (e.g., blooming of flowers, etc.).","Optionally, some occupants who watched the video related to the unhindered FOV for long periods (or have a physical window) may be monitored to see when an interesting view is encountered.","Points of interest may involve items identified in the exterior environment using image analysis, including presenting the VST when one or more of the following happens: passing a fancy vehicle, passing someone the occupant knows, passing a vehicle accident, passing a police officer, having a sunset view, and passing an animal the occupant is interested in.","In one embodiment, the system may receive an indication that the occupant is feeling at least one of nauseous and claustrophobic, and consequently present the VST in order to help the occupant to confront the feeling.","For example, when there is a serious spike (e.g., increase in heart-rate and sweating), then the system may present the VST automatically.","The system may also present a “normal” interior to the occupant (e.g., natural lighting settings).","Optionally, when digital content is consumed (e.g., a game or a movie), the system may check whether the affective spike (e.g., increased excitement) is due to the content or due to the experience of being in the vehicle with AR or VR.","If it is the former case, then the system might not present the VST.","Some aspects of this disclosure involve an autonomous on-road vehicle that includes a nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) that is coupled to the compartment of the vehicle and is located, during normal driving, at eye level in front of an occupant who sits in a front seat of the vehicle.","Additionally, the vehicle includes a stiff element that is configured to support the SAEDP and to resist deformation during collision in order to reduce compartment intrusion.","The stiff element is located, during normal driving, at eye level between the SAEDP and the outside environment.","Thus, the combination of the SAEDP and the stiff element offers the occupant an increased level of protection, e.g., in the case of a collision, compared to a vehicle in which a traditional window is in place at eye level in the front of the vehicle.","However, due to it being nontransparent, placing the SAEDP at eye level may obstruct the occupant's view to the outside.","Thus, in order to offer the occupant such a view, in some embodiments, the vehicle also includes a camera configured to take video of the outside environment in front of the occupant, and a computer configured to generate, based on the video, a representation of the outside environment in front of the occupant at eye level.","This representation may be provided to the occupant using various types of displays.","One non-limiting advantage of the vehicle described above is that it increases the safety of the occupant in the case of a collision, without prohibiting the occupant from obtaining a view of the outside environment.","In one embodiment, an autonomous on-road vehicle includes a compartment, which one or more occupants may occupy while traveling in the vehicle (e.g., by sitting in seats).","Coupled to the front of the compartment is a Shock-Absorbing Energy Dissipation Padding (SAEDP) and a stiff element that supports the SAEDP.","Optionally, the SAEDP is nontransparent.","The stiff element is located, during normal driving, at eye level between the SAEDP and the outside environment.","Additionally, the vehicle includes a camera (e.g., camera 142 or structure 147 that comprises multiple cameras), which is configured to take video of the outside environment in front of the occupant, and a computer (e.g., computer 143) that is configured to generate, based on the video, a representation of the outside environment in front of the occupant at eye level.","Optionally, the camera, and/or each of the cameras in the structure 147, may be based on at least one of the following sensors: a CCD sensor, a CMOS sensor, a near infrared (NIR) sensor, an infrared sensor (IR), and a device based on active illumination such as a LiDAR.","Optionally, when the camera comprises multiple cameras, the multiple cameras are directed to multiple directions around the vehicle, and the multiple cameras support generating multiple representations of the outside environment from different points of view.","It is to be noted that in some embodiments, the SAEDP may be fixed at its location both in normal driving and in times that are not considered to correspond to normal driving, while in other embodiments, the SAEDP may change its location during at least some of the times that do not correspond to normal driving.","The SAEDP is coupled to the compartment in such a way that it is located, during normal driving, at eye level in front of an occupant who sits in a front seat of the vehicle.","Different types of SAEDPs may be utilized in different embodiments.","In one embodiment, the SAEDP comprises a passive material that is less stiff than a standard automotive glass window.","The passive material is configured to protect the occupant's head against hitting the inner side of the vehicle compartment during a collision.","Optionally, the passive material has thickness greater than at least one of the following thicknesses: 1 cm, 2 cm, 5 cm, 10 cm, 15 cm, and 20 cm.","Optionally, the thickness of the passive material may refer to the average thickness of the SAEDP across the portion of the SAEDP at eye level.","Alternatively, the thickness may refer to the maximal thickness at some position of the SAEDP (which is at least one of the values mentioned above).","In another embodiment, the SAEDP comprises a pneumatic pad that is configured to inflate in order to protect the occupant's head against hitting the inner side of the vehicle compartment during collision.","In some examples, the pneumatic pads may be formed from an elastomeric material providing chambers containing air or another gas.","Optionally, the chambers are retained in compressed deflated condition until being inflated by the admission of gas pressure controlled by the vehicle's autonomous-driving control system that is responsible to estimate the probability and severity of an imminent collision.","Additionally or alternatively, the chambers may be provided with restricted passages limiting the flow out from the chambers to provide shock-absorbing energy dissipation to reduce the rebound effect.","U.S. Pat.","No.","5,382,051 discloses examples for pneumatic pads that can be used with some of the embodiments.","In yet another embodiment, the SAEDP comprises an automotive airbag, which is configured to protect the occupant's head against hitting the inner side of the vehicle compartment during collision.","In one example, during normal driving, the airbag is in a stowed state.","The airbag is coupled to an inflator configured to inflate the airbag with gas to an inflated state, upon receiving an indication indicative of a probability of an impact of the vehicle exceeding a threshold.","In this example, the airbag is located, when in the stowed state, at eye level in front of the occupant.","In some embodiments, the compartment may include a door, and the SAEDP is physically coupled to the door from the inside, such that the SAEDP moves with the door as the door opens and/or closes.","In some embodiments, the vehicle may include a second SAEDP coupled to the outer front of the vehicle to minimize damage to a pedestrian during a pedestrian-vehicle collision.","In one embodiment, the stiff element that supports the SAEDP is nontransparent.","In another embodiment, the stiff element may be automotive laminated glass or automotive tempered glass.","Optionally, the structure of the vehicle comprises a crumple zone located at eye level between the stiff element and the outside environment.","The representation of the outside environment is intended to provide the occupant with some details describing the outside environment.","In some embodiments, the representation of the outside environment is generated from the point of view of the occupant, and it represents how a view of the outside environment would look like to the occupant, had there been a transparent window at eye level instead of the SAEDP and/or the stiff element.","Optionally, a display is utilized to present the representation to the occupant.","Various types of displays may be utilized in different embodiments to present the representation of the outside environment to the occupant.","In one embodiment, the display is comprised in an HMD, and the vehicle further comprises a communication system configured to transmit the representation to the HMD.","For example, the HMD may be a virtual reality system, an augmented reality system, or a mixed-reality system.","In one embodiment, the display is supported by at least one of the SAEDP and the stiff element.","For example, the display is physically coupled to the SAEDP and/or the stiff element.","Optionally, the display is a flexible display.","For example, the flexible display may be based on at least one of the following technologies and their variants: OLED, organic thin film transistors (OTFT), electronic paper (e-paper), rollable display, and flexible AMOLED.","In one example, the display is flexible enough such that it does not degrade the performance of the SAEDP by more than 20% during a collision.","In one example, the performance of the SAEDP is measured by hitting a crash test dummy head against the SAEDP and measuring the head's deceleration using sensors embedded in the head.","FIG.","21a, FIG.","21b, and FIG.","22 illustrate various embodiments of the vehicle described above.","Each of the illustrated vehicles comprises a cross-section view of the vehicles, where each includes a compartment 145 for a single occupant (in FIG.","21b) or more (in FIG.","21a and FIG.","22).","In the figures, much of the compartment is covered with the SAEDP 140, which is nontransparent and comprises a soft passive material (cushiony in its nature).","Supporting the SAEDP 140 is a stiff element 141, which in the illustrations comprises portions of the exterior (hull) of the vehicle which may optionally be made of one or more of the following materials: fiber-reinforced polymer, carbon fiber reinforced polymer, steel, and aluminum.","The vehicles also include a camera (such as camera 142 and/or structure 147 that houses multiple cameras), which is positioned to capture a front view of the outside environment of the vehicle.","Additionally, the vehicles include a computer 143, which may be positioned in various locations in the vehicle.","In some embodiments, the computer may be comprised of multiple processors and/or graphics processors that may be located at various locations in the vehicle.","The figures illustrate various types of displays that may be utilized to present the occupant with the representation of the outside environment generated by the computer 143 based on the video taken by the camera 142.In FIG.","21a the representation is presented via an HMD 144, which may be, for example, a virtual reality HMD.","In FIG.","21b the representation is presented via an HMD 146, which may be, for example, a mixed-reality headset.","And in FIG.","22 the representation may be provided via one or more of the displays 150, which are coupled to the compartment.","It is to be noted that in the figures described above not all of the described elements appear in each figure.","The figures also illustrate various structural alternatives that may be implemented in different embodiments described herein.","For example, FIG.","21a illustrates a vehicle that includes window 148, which may optionally be an automotive tempered glass window, located in a location in which the head of a belted occupant is not expected to hit during collision.","FIG.","21b illustrates a vehicle that includes crumple zone 149, which is located at the front of the vehicle at eye level.","The figure also illustrates the structure 147 that houses multiple cameras directed to multiple directions around the vehicle.","In some embodiments, the representation of the outside environment may be manipulated in order to improve how the outside environment looks to the occupant.","Optionally, this may be done utilizing the computer.","In one example, manipulating the representation includes at least one of the following manipulations: converting captured video of an overcast day to video of a sunny day by preserving main items in the captured video (such as vehicles and buildings) and applying effects of a sunny day, converting unpleasant environment to a nice one, converting standard vehicles to futuristic or old fashion vehicles, and adding fans standing outside and waiving to the occupant.","In one embodiment, the manipulation maintains the main items in the environment, such that the occupant would still know from the manipulated representation where he/she is traveling.","In another embodiment, the manipulated representation maintains the main objects in the video of the outside environment, such that the main objects presented in the manipulated video essentially match the main objects that would have been seen without the manipulation.","In some embodiments, the vehicle compartment may include an automotive laminated glass window or automotive tempered glass window located in a location where the head of a belted occupant is not expected to hit as a result of collision while traveling in velocity of less than 50 km/h, as illustrated by the dotted rectangle 148 in FIG.","21a.","In one embodiment, the structure of the vehicle is such that a crumple zone is located at eye level between the stiff element and the outside environment.","Various types of vehicles may benefit from utilization of the nontransparent SAEDP supported by the stiff element and in conjunction with the camera and computer, as described above.","The following are some examples of different characterizations of vehicles in different embodiments.","In one embodiment, the vehicle weighs less than 1,500 kg without batteries, and it is designed to carry up to five occupants.","In another embodiment, the vehicle weighs less than 1,000 kg without batteries, and it comprises an engine that is able to sustain continuously at most 80 horsepower.","In yet another embodiment, the vehicle weighs less than 1,000 kg and it is designed to carry up to two occupants.","In still another embodiment, the vehicle weighs less than 800 kg without batteries, and it comprises an engine that is able to sustain continuously at most 60 horsepower.","In yet another embodiment, the vehicle weighs less than 500 kg without batteries and it comprises an engine that is able to sustain continuously at most 40 horsepower.","And in still another embodiment, the vehicle weighs less than 400 kg without batteries and is designed to carry up to two occupants.","Some aspects of this disclosure involve an autonomous on-road vehicle that includes a nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) that is coupled to the compartment and is located, during normal driving, at eye level to the left of the occupant who sits in a front seat of the vehicle (in the left front seat when the vehicle has more than one front seat).","The SAEDP obstructs at least 30 degrees out of the horizontal unaided field of view (FOV) to the outside environment to the left of the occupant at eye level.","Additionally, the vehicle includes a stiff element that is configured to support the SAEDP and to resist deformation during collision in order to reduce compartment intrusion.","The stiff element is located, during normal driving, at eye level between the SAEDP and the outside environment.","Thus, the combination of the SAEDP and the stiff element offers the occupant an increased level of protection, e.g., in the case of a collision to the left side of the vehicle, compared to a vehicle in which a traditional window is in place at eye level on the left side of the vehicle.","However, due to it being nontransparent, placing the SAEDP at eye level may obstruct the occupant's view to the outside.","Thus, in order to offer the occupant such a view, in some embodiments, the vehicle also includes a camera configured to take video of the outside environment to the left of the occupant, and a computer, which is configured to generate, based on the video, a representation of the outside environment to the left of the occupant at eye level.","This representation may be provided to the occupant using various types of displays.","One non-limiting advantage of the vehicle described above is that it increases the safety of the occupant in the case of a side collision, without prohibiting the occupant from obtaining a side view of the outside environment.","In one embodiment, an autonomous on-road vehicle includes a compartment, which one or more occupants may occupy while traveling in the vehicle (e.g., by sitting in seats).","Coupled to the compartment is a Shock-Absorbing Energy Dissipation Padding (SAEDP) and a stiff element that supports the SAEDP.","Optionally, the SAEDP is nontransparent.","The SAEDP is located, during normal driving, at eye level to the left of the occupant who sits in a front seat of the vehicle.","The stiff element is located, during normal driving, at eye level between the SAEDP and the outside environment.","Optionally, the stiff element is nontransparent.","Optionally, the stiff element may be automotive laminated glass or automotive tempered glass.","The vehicle also includes a camera (such as camera 161) that is configured to take video of the outside environment to the left of the occupant, and a computer that is configured to generate, based on the video, a representation of the outside environment to the left of the occupant at eye level.","Optionally, the camera comprises multiple cameras directed to multiple directions around the vehicle, and the multiple cameras support generating multiple representations of the outside environment from different points of view.","FIG.","23 illustrates one embodiment of the autonomous on-road vehicle described above, which shows how an SAEDP protects the occupant during a collision.","In the figure, SAEDP 160 (which may comprise a passive material) is coupled to the stiff element 141.When another vehicle collides with the side of the vehicle, the occupants head strikes the soft SAEDP 160, instead of a glass window (which would be positioned there in many conventional vehicles).","The SAEDP is coupled to the compartment in such a way that it is located, during normal driving, at eye level to the left of the occupant who sits in a front seat of the vehicle.","Optionally, due to its location, the SAEDP obstructs at least 30 degrees out of the horizontal unaided field of view (FOV) to the outside environment to the left of the occupant at eye level.","Optionally, the SAEDP obstructs at least 45 degrees or at least 60 degrees out of the horizontal unaided FOV to the outside environment to the left of the occupant at eye level.","In one example of a standard vehicle, such as Toyota Camry model 2015, the frontal horizontal unaided FOV extends from the left door through the windshield to the right door.","In some embodiments, the SAEDP is fixed to the left door of the vehicle.","In one embodiment, the vehicle has a single seat (occupied by the occupant).","In another embodiment, the vehicle has two or more front seats and the occupant occupies the leftmost of the two or more front seats.","Different types of SAEDPs may be utilized in different embodiments.","In one embodiment, the SAEDP comprises a passive material, which is less stiff than a standard automotive glass window, having a thickness greater than at least one of the following thicknesses: 1 cm, 2 cm, 5 cm, 10 cm, 15 cm, and 20 cm.","In other embodiments, the SAEDP may include an automotive airbag or a pneumatic pad that is configured to inflate in order to protect the occupant's head against hitting the inner side of the vehicle compartment during collision.","In a similar fashion to how the SAEDP and stiff element are utilized to help protect the left side of the occupant, the same setup may be applied to the right side of the vehicle, in order to help protect that side.","Thus, in some embodiments, the vehicle may further include a second SAEDP located at eye level to the right of the occupant who sits in the front seat, and a second stiff element located at eye level between the second SAEDP and the outside environment.","Optionally, the second SAEDP obstructs at least 20 degrees out of the horizontal unaided FOV to the outside environment to the right of the occupant at eye level, and the computer is further configured to generate a second representation of the outside environment to the right of the occupant.","Some aspects of this disclosure involve an autonomous on-road vehicle that includes a nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) that can cover a side window that enables an occupant of the vehicle to see the outside environment.","The side window is located at eye level of an occupant who sits in the vehicle.","A motor is configured to move the SAEDP over a sliding mechanism between first and second states multiple times without having to be repaired.","A processor is configured to receive, from an autonomous-driving control system, an indication that a probability of an imminent collision reaches a threshold, and to command the motor to move the SAEDP from the first state to the second state.","In the first state the SAEDP does not block the occupant's eye level view to the outside environment, and in the second state the SAEDP blocks the occupant's eye level view to the outside environment in order to protect the occupant's head against hitting the side window during collision.","One non-limiting advantage of the vehicle described above is that it increases the safety of the occupant in the case of a side collision.","In one embodiment, an autonomous on-road vehicle includes a side window 170, a nontransparent SAEDP (e.g., SAEDP 171), a motor 172, and a processor 175.The processor 175 is configured to receive, from an autonomous-driving control system (such as autonomous-driving control system 65), an indication indicating that a probability of an imminent collision reaches a threshold, and to command the motor 172 to move the SAEDP 171 from the first state to the second state.","In the first state the SAEDP 171 does not block the occupant's eye level view to the outside environment, and in the second state, the SAEDP 171 blocks the occupant's eye level view to the outside environment in order to protect the occupant's head against hitting the side window during collision.","Optionally, the processor is configured to command the motor 172 to start moving the SAEDP 171 to the second state at least 0.2 second, 0.5 second, 1 second, or 2 seconds before the expected time of the collision.","The motor 172 is configured to move the SAEDP 171 over a sliding mechanism 173 between first and second states multiple times without having to be repaired.","For example, during the same voyage, the SAEDP 171 may go up and down multiple times without a need for the occupant or anyone else to repair the SAEDP 171 and/or other components (such as motor 172 or the window 170) in order to the SAEDP 171 to be able to continue its operation correctly (i.e., continue moving up and down when needed).","In some examples, the motor 172 is a motor designed to move the SAEDP 171 more than twice, more than 100 times, and/or more than 10,000 times without being replaced.","The side window 170 is located at eye level of an occupant who sits in the vehicle, which enables the occupant to see the outside environment.","In one embodiment, the side window 170 is a power window.","In this embodiment, the power window comprises a window regulator that transfers power from a window motor 177 to the side window glass in order to move it up or down.","The motor 172 is coupled to an SAEDP regulator that transfers power from the motor 172 to the SAEDP 171 in order to move it up or down.","In this embodiment, the SAEDP regulator is located closer to the inner side of the compartment then the window regulator.","Optionally, the motor 172 and the window motor 177 may be of the same type or of different types.","In one embodiment, the SAEDP 171 comprises a passive material, which is less stiff than a standard automotive glass window, having thickness greater than at least one of the following thicknesses: 1 cm, 2 cm, 5 cm, 10 cm, 15 cm, and 20 cm.","Optionally, the vehicle may include a storage space in a door of the vehicle, which is configured to store the SAEDP 171 in the first state.","Additionally or alternatively, the vehicle may include a storage space in the roof of the vehicle, which is configured to store the SAEDP 171 in the first state.","Optionally, the SAEDP 171 may move upwards when switching between the first and second states, and the top of the SAEDP has a profile (such as a triangle or a quarter sphere) which reduces the risk of catching the a part of the occupant (e.g., a finger or limb) or the occupant's clothing, between the top of the SAEDP 171 and an upper frame when moving the SAEDP 171 to the second state.","In one embodiment, when switching the SAEDP 171 quickly between the first and second states, the SAEDP 171 is configured not to cover a range of 1 to 5 cm of the top height of the window.","Optionally, keeping said range unoccupied reduces the risk of catching the occupant's fingers or limb by the edge of the SAEDP 171 when moving the SAEDP 171 to the second state.","In some embodiments, the vehicle may include additional SAEDPs that cover additional regions of the vehicle's compartment (besides the side window 170).","In one example, the vehicle includes an SAEDP 176 that covers at least a portion of the roof of the vehicle.","In some embodiments, the vehicle includes a camera (e.g., camera 178a), which is configured to take video of the outside environment while the SAEDP 171 is in the second state.","Additionally, in these embodiments, the vehicle may include a computer (such as computer 13), which is configured to generate a representation of the outside environment based on the video, and a display configured to present the representation of the outside environment to the occupant.","The display may be physically coupled to the compartment and/or belong to an HMD.","Optionally, the camera is fixed to the SAEDP 171, and thus moves along with the SAEDP 171 when it is moved between the first and second states.","Optionally, the display is fixed to the SAEDP 171, and thus moves along with the SAEDP 171 when it is moved between the first and second states.","Optionally, the display is configured to show, at eye level, a representation of the outside environment when the SAEDP is in the second state.","In one example, the display is a flexible display.","In another example, the camera comprises multiple cameras directed to multiple directions around the vehicle, and the computer is configured to generate at least two different representations of the outside environment, from at least two different points of view, for two occupants who sit in the vehicle.","In some embodiments, in addition to raising the SAEDP 171, one or more of the displays mentioned above is utilized to present the occupant a video of the threat and the predicted trajectory that could result in the collision, in order to explain why the SAEDP 171 is being moved to the second state.","FIG.","24a and FIG.","24b illustrate an example of a vehicle in which the side window may be covered by an SAEDP that can move up and down.","The figures illustrate cross-sections of the vehicle, which show how the SAEDP 171 may move from the first state (in FIG.","24a) to the second state (in FIG.","24b).","The dotted line 179 indicates that the SAEDP 171 does not close the entire gap over the window (e.g., in order to avoid catching the occupant's hair).","The figures also illustrate sliding mechanism 173, which may be utilized to guide and assist in the movement of SAEDP 171.FIG.","24b also illustrates camera 178a and display 178b, which are connected to a processor that generates, based on the video received from the camera, a view of the outside environment when an SAEDP (on the right side of the vehicle) is in the second state.","The view of the outside environment is presented to the occupant on the display 178b.","Camera and display on the left SAEDP 171, which correspond to camera 178a and display 178b, are not shown in the figure in order to make it clearer; however it is to be understood that such camera and display may be fitted to any relevant moving SAEDP.","In one embodiment, the mechanism that moves the SAEDP 171 between the first and second states (referred to as the “SAEDP mechanism”) is similar to a power window regulator that moves an automobile window up and down.","As with automobile power windows, the SAEDP regulator may be powered by an electric motor, which may come with the SAEDP regulator as one unit, or as a system that enables the motor or regulator to be replaced separately.","The SAEDP mechanism includes a control system, a motor, a gear reduction, a sliding mechanism and the SAEDP, which are usually fixed on the door, but may alternatively be fixed on the roof as disclosed below.","The sliding mechanism may have different architectures, such as Bowden type, double Bowden type, cable spiral, or crossed levers.","In a first example, the SAEDP mechanism is similar to a double Bowden power window mechanism, in which the SAEDP 171 is fixed on two supports respectively constrained along two rails.","The control system drives the motor that wraps two Bowden cables, which move two supports and, consequently, the SAEDP 171.A Bowden cable transmits mechanical force through the movement of an inner cable relative to an outer housing, and in the case of a DC motor, the basic operations of the motor are accomplished by reversing the polarity of its power and ground input.","In a second example, the SAEDP mechanism is similar to a gear-drive type power window regulator; in this case, the SAEDP mechanism includes an SAEDP motor to power the mechanism, gear drive and geared arm to move the SAEDP 171 between the first and second states, and an SAEDP holding bracket to hold the SAEDP 171.In a third example, the SAEDP mechanism is similar to a cable type power window regulator; in this case, the SAEDP regulator includes an SAEDP motor that drives a wire cable though a mechanism, a series of pulleys that guide the cable, and a regulator carriage attached to the cable and to the SAEDP 171 and slides on the regulator track.","One or more tracks may be mounted vertically inside the door panel that serves as a guide piece when the SAEDP 171 slides up and down.","Depending on the design, the setup may have one main regulator track in the center of the door, or have a track on each side of the SAEDP.","In a fourth example, the SAEDP regulator is similar to a scissor power window regulator; in this case, a motor operates a gear wheel that raises and lowers the SAEDP 171 by the use of a scissor action of rigid bars.","The motor that moves the SAEDP 171 over the sliding mechanism may be any suitable motor, such as a DC electric motor, an AC electric motor, or a pneumatic motor.","In one embodiment, the indication that the probability of an imminent collision reaches a threshold is received from the autonomous-driving control system 65 that calculates the probability based on the trajectory of the vehicle and information about the road.","Optionally, the information about the road may be received from one of more of the following sources: a sensor mounted to the vehicle, a sensor mounted on a nearby vehicle, a road map, a stationary traffic controller nearby the vehicle, and a central traffic controller that communicates with the vehicle via wireless channel.","In one embodiment, the processor 175 is further configured to receive an updated indication that the probability of the imminent collision does not reach a second threshold, and to command the motor to move the SAEDP to the first state.","In this embodiment, the second threshold denotes a probability for a collision that is equal or lower than the threshold.","FIG.","25a and FIG.","25b illustrate a motor configured to move a front nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) between first and second states.","Some aspects of this disclosure involve an autonomous on-road vehicle that includes an outer nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) mounted to the front side of the vehicle during normal driving, such that the SAEDP is in front of and at eye level of an occupant who sits in a front seat of the vehicle.","Additionally, the vehicle includes a camera that is mounted to the vehicle and is configured to take video of the outside environment in front of the occupant, and a computer configured to generate, based on the video, a representation of the outside environment at eye level for the occupant.","One non-limiting advantage of the vehicle described above is that it increases the safety of a pedestrian in case of a vehicle-pedestrian collision, without prohibiting the occupant of the vehicle from receiving a frontal view of the outside environment.","FIG.","26a illustrates one embodiment of an autonomous on-road vehicle that includes outer nontransparent SAEDP 190, which is mounted to the front side of the vehicle during normal driving, such that the SAEDP 190 is in front of and at eye level of an occupant who sits in a front seat of the vehicle.","The SAEDP 190 is less stiff than a standard automotive glass window and is designed to absorb some of the crashing energy transmitted to a pedestrian during a pedestrian-vehicle collision.","Additionally, the vehicle includes a camera (such as camera 142), which is mounted to the vehicle and is configured to take video of the outside environment in front of the occupant, and a computer (such as computer 143), which is configured to generate, based on the video, a representation of the outside environment at eye level for the occupant.","Optionally, the representation is generated from the point of view of the occupant.","Optionally, the vehicle includes a display configured to present the representation to the occupant.","For example, the display may belong to an HMD worn by the occupant.","In another example, the display may be coupled to the compartment of the vehicle, and may be a flexible display.","The SAEDP 190 may be implemented utilizing various approaches in different embodiments described herein.","In one embodiment, the SAEDP 190 comprises a passive material.","Optionally, the SAEDP 190 has thickness greater than at least one of the following thicknesses: 1 cm, 2 cm, 5 cm, 10 cm, 15 cm, and 20 cm.","In another embodiment, the SAEDP 190 comprises an automotive airbag configured to inflate in order to protect the pedestrian.","FIG.","26b illustrates an outer SAEDP 190 that includes two air bags 192 configured to absorb some of the crashing energy transmitted to a pedestrian during a pedestrian-vehicle collision.","Optionally, the airbag has a stowed condition and an inflated condition.","The airbag is coupled to an inflator configured to inflate the airbag with gas, and the airbag is located, in the stowed condition, at eye level in front of the occupant.","In this embodiment, the vehicle further includes an autonomous-driving control system, such as autonomous-driving control system 65, which is configured to calculate a probability of pedestrian-vehicle collision, based on measurements of sensors mounted to the vehicle, and to command the airbag to inflate before the pedestrian head hits the vehicle.","In yet another embodiment, the SAEDP 190 comprises a pneumatic pad configured to inflate in order to protect the pedestrian.","In this embodiment, the vehicle further includes an autonomous-driving control system, such as autonomous-driving control system 65, which is configured to calculate a probability of pedestrian-vehicle collision, based on measurements of sensors mounted to the vehicle, and to command the pneumatic pad to start inflate at least 0.5 second before the expected time of the collision in order to protect the pedestrian.","Optionally, the pneumatic pad is reusable, and can be used multiple times without the need to be repaired.","For example, the vehicle comprises a mechanism to deflate and/or stow the pneumatic pad, without requiring its repair and/or replacement.","Some aspects of this disclosure involve an autonomous on-road vehicle that includes a window located at eye level of an occupant who sits in a front seat of the vehicle (e.g., a windshield), a reusable nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP), a motor, and a processor.","The window enables the occupant to see the outside environment.","The motor is configured to move the SAEDP over a sliding mechanism between first and second states multiple times without having to be repaired.","In the first state the SAEDP does not block the occupant's eye level frontal view to the outside environment, and in the second state the SAEDP blocks the occupant's eye level frontal view to the outside environment.","Additionally, in the second state the SAEDP can absorb some of the crashing energy transmitted to a pedestrian during a pedestrian-vehicle collision.","The processor is configured to receive, from an autonomous-driving control system, an indication indicative of whether a probability of an imminent pedestrian-vehicle collision reaches a threshold.","Responsive to receiving an indication of an imminent collision (e.g., within less than 2 seconds), the processor is configured to command the motor to move the SAEDP from the first state to the second state.","One non-limiting advantage of the vehicle described above is that it increases the safety of a pedestrian in case of a vehicle-pedestrian collision, without prohibiting the occupant of the vehicle from receiving a frontal view of the outside environment during normal driving.","FIG.","27a and FIG.","27b illustrate one embodiment of a motorized external SAEDP 121 that can move between first and second states multiple times.","The figures illustrate how the SAEDP 121 can move from the first state (in FIG.","27a), in which the SAEDP is stored above the windshield, to the second state (FIG.","27b), in which the SAEDP is located in front of the windshield, by having the motor 122 move the SAEDP 121 optionally over a sliding mechanism 123.Additionally, the figures illustrate optional camera 126 that is embedded in the SAEDP 121, and which may provide video to a processor configured to generate a representation of the outside environment when the SAEDP 121 is in the second state.","In one embodiment, an autonomous on-road vehicle includes window 120, reusable SAEDP 121, motor 122, and processor 124.The window 120, which is located at eye level of an occupant who sits in a front seat of the vehicle, and which may be a windshield, enables the occupant to see the outside environment.","The SAEDP 121 is reusable, i.e., it may be moved multiple times without the need to replace it or repair it after each use.","The SAEDP 121 may be implemented utilizing various approaches in different embodiments described herein.","In one embodiment, the SAEDP 121 comprises a passive material.","Optionally, the SAEDP 121 has thickness greater than at least one of the following thicknesses: 1 cm, 2 cm, 5 cm, 10 cm, 15 cm, and 20 cm.","In another embodiment, the SAEDP 121 comprises a pneumatic pad configured to inflate in order to protect the pedestrian.","Optionally, the pneumatic pad is reusable, and the processor 124 is configured to command the pneumatic pad to start inflate at least 0.5 second before the expected time of the pedestrian-vehicle collision.","The motor 122 is configured to move the SAEDP 121, optionally over a sliding mechanism 123, between first and second states multiple times without having to be repaired.","In the first state the SAEDP 121 does not block the occupant's eye level frontal view to the outside environment, and in the second state the SAEDP 121 blocks the occupant's eye level frontal view to the outside environment.","When in the second state, the SAEDP 121 is configured to absorb some of the crashing energy transmitted to a pedestrian during a pedestrian-vehicle collision.","The SAEDP may be stored above or below the windshield 120.FIG.","27a illustrates one embodiment of storing the SAEDP above the windshield.","In another embodiment, the SAEDP is stored below the windshield.","Optionally, the SAEDP is stored below the windshield in two layers, and shortly before an imminent pedestrian-vehicle collision the first layer stays below the windshield while the second layer is moved by a motor to a location in front of the windshield.","Alternatively, the SAEDP is stored below the windshield in a folded manner, and shortly before an imminent pedestrian-vehicle collision the folded SAEDP is stretched by a motor to cover the windshield at least until the occupant's eye level.","The processor 124 is configured to receive, from an autonomous-driving control system (such as autonomous-driving control system 65), an indication indicative of whether a probability of an imminent pedestrian-vehicle collision reaches a threshold.","Optionally, most of the time the vehicle travels, the processor 124 does not provide an indication that the probability reaches the threshold.","Responsive to receiving an indication of an imminent collision (e.g., within less than 2 seconds), the processor 124 is configured to command the motor 122 to move the SAEDP 121 from the first state to the second state.","Optionally, the processor 124 is configured to command the motor to start moving the SAEDP 121 to the second state at least 0.2 second, 0.5 second, 1 second, or 2 seconds before the pedestrian-vehicle collision in order to protect the pedestrian.","In one example, the vehicle includes a sensor configured to detect the distance and angle between the vehicle and a pedestrian, and the autonomous-driving control system calculates the probability of the imminent pedestrian-vehicle collision based on the data obtained from the sensor, the velocity of vehicle and the possible maneuver.","In one embodiment, the processor 124 is further configured to receive an updated indication that indicates the probability of the imminent pedestrian-vehicle collision does not reach a second threshold, and to command the motor 122 to move the SAEDP to the first state.","Optionally, the second threshold denotes a probability for a pedestrian-vehicle collision that is equal or lower than the threshold.","In one embodiment, the vehicle includes a camera (such as camera 126), which is configured to take video of the outside environment while the SAEDP 121 is in the second state.","Additionally, in this embodiment, the vehicle may further include a computer configured to generate, based on the video, a representation of the outside environment, and a display configured to present the representation of the outside environment to the occupant while the SAEDP 121 is in the second state.","Optionally, the camera 126 is fixed to the SAEDP 121 from the outer side, and thus moves with the SAEDP 121 when it moves between the first and second states.","Optionally, the display is fixed to the SAEDP 121 from the inner side, and thus also moves with the SAEDP 121 when it moves between the first and second states; the occupant can see the display via the window 120 when the SAEDP is in the second state.","In an alternative embodiment, the display is physically coupled to the compartment (such as a windshield that also functions as a display) and/or comprised in an HMD worn by the occupant.","In addition to, or instead of, moving an SAEDP when a collision is imminent, in some embodiments, an imminent collision may prompt a raise of one or more power windows in the vehicle.","This approach is illustrated in the following embodiment.","In one embodiment, a safety system for an occupant of an autonomous on-road vehicle includes an automobile power window and an autonomous-driving control system (such as autonomous-driving control system 65).","The autonomous-driving control system is configured to calculate probability of an imminent collision based on data received from sensors coupled to the vehicle.","Responsive to detecting that the probability reaches a threshold, and at least one second before the expected collision, the autonomous-driving control system commands the power window to rise.","In this embodiment, a raised power window provides an improved safety for the occupant of the vehicle during collision compared to a lowered power window.","Optionally, responsive to detecting that the probability reaches the threshold, and at least two seconds before the expected collision, the autonomous-driving control system is configured to command the power window to rise.","In one embodiment, the vehicle further includes an SAEDP coupled to the power window from the inside (e.g., as illustrated in FIG.","24a and FIG.","24b).","In one embodiment, the power window is nontransparent, and the safety system for the occupant includes a display coupled to the power window from the inside.","The display is configured to present to the occupant a video see-trough (VST) of the outside environment that is generated based on a video camera pointed at the outside environment.","In another embodiment, the power window is made of a nontransparent material, which is stronger than a standard automotive tempered glass having the same dimensions.","In this embodiment, the vehicle further comprises a camera configured to take video of the outside environment (such as camera 178a), and a computer configured to generate a VST to the outside environment based on the video.","Optionally, the camera is physically coupled to the power window, such that the camera is raised and lowered with the power window.","Additionally or alternatively, the camera may be coupled to an element of the vehicle that is not the power window, such that the camera does not move up and down when the power window is raised and lowered.","Optionally, the vehicle further includes a display coupled to the inner side of the power window, such that the display is at eye level when the power window is raised, and below eye level when the power window is lowered; the display is configured to present the VST to the occupant.","Optionally, the occupant wears an HMD, and the computer is configured to present the VST to the occupant on the HMD when the power window is raised, and not to present the VST to the occupant on the HMD when the power window is lowered.","With autonomous vehicles, it is not necessary for occupants to sit.","Some aspects of this disclosure involve autonomous vehicles in which an occupant of the vehicle may lay down.","Such a design for an autonomous vehicle has the advantage of enabling a more comfortable position for certain activities (e.g., relaxing or sleeping).","Additionally, such a vehicle may be built to be lower than traditional vehicles, which can offer advantages in terms of increased safety (e.g., a lower center of gravity offers better stability) and better vehicle aerodynamics.","In order to increase the safety of the occupant, various forms of padding may be used in the compartment of the vehicle.","In some embodiments, an autonomous on-road vehicle designed for lying down includes a closed compartment and a mattress, having an average thickness of at least 3 cm, which covers at least 50% of the compartment floor.","In the compartment, there is a nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP), having an average thickness of at least 1 cm, which covers at least 50% of the compartment side walls and at least 60% of the compartment front wall during normal driving.","Optionally, the SAEDP is supported by a stiff element that resists deformation during a collision in order to reduce compartment intrusion.","Additionally, the vehicle includes a camera configured to take video of the outside environment, a computer configured to generate a representation of the outside environment based on the video, and a display configured to present the representation to the occupant.","In one embodiment, an autonomous on-road vehicle designed for lying down includes a closed compartment 210, a mattress 211, an SAEDP 212 covering portions of the compartment 210, a camera (e.g., the structure 147 that houses multiple cameras), a computer (e.g., the computer 143), and a display 215.FIG.","28 illustrates one embodiment of a vehicle compartment 210 in which an occupant may lay down.","In the figure, the occupant is lying down on mattress 211, which covers the floor of the compartment 210, and is watching a movie on the display 215.The SAEDP 212 covers the front, roof, and back of the compartment 210.It is to be noted that the SAEDP 212 also covers portions of the side walls of the compartment 210, however, this is not illustrated to enable a clearer image of the embodiment.","The figure also includes an airbag 216, which may be inflated below the SAEDP 212 in order to protect the occupant and restrain his/her movement in the case of a collision.","The mattress 211 covers at least 50% of the compartment floor.","Optionally, the mattress 211 covers at least 80% of the compartment floor.","In one embodiment, the mattress 211 has an average thickness of at least 3 cm.","In other embodiments, the average thickness of the mattress 211 is greater than at least one of the following thicknesses: 5 cm, 7 cm, 10 cm, 20 cm, and 30 cm.","The SAEDP 212 is a nontransparent SAEDP, having an average thickness of at least 1 cm.","Optionally, the SAEDP 212 covers at least 50% of the compartment side walls and at least 60% of the compartment front wall during normal driving.","In one embodiment, the average thickness of the SAEDP 212 is greater than at least one of the following thicknesses: 2 cm, 3 cm, 5 cm, 10 cm, 15 cm, and 20 cm.","In another embodiment, the SAEDP 212 covers at least 80% of the compartment side walls and at least 80% of the compartment front wall.","In yet another embodiment, the SAEDP covers at least 50% of the compartment roof.","In still another embodiment, the mattress and the SAEDP cover essentially the entire compartment interior.","In addition to the SAEDP 212, in some embodiments additional measures may be employed in order to improve the safety of the occupant.","In one embodiment, the vehicle includes an automotive airbag configured to deploy in front of the SAEDP 212 in order to protect the occupant, in addition to the SAEDP 212, against hitting the inner side of the vehicle compartment during a collision.","It is noted that the meaning that the airbag deploys in front of the SAEDP is that the airbag deploys towards the inner side of the compartment.","Optionally, the airbag has a stowed condition and an inflated condition, and the airbag is coupled to an inflator configured to inflate the airbag with gas upon computing a predetermined impact severity.","The stowed airbags may be stored in various positions, such as stored essentially in the middle of the front wall, stored essentially in the middle of the rear wall, stored in the side walls (possibly two or more horizontally spaced airbags), and stored in the roof (possibly one or more airbags towards the front of the compartment and one or more airbags towards the rear of the compartment).","In some embodiments, various additional safety measures may be utilized to improve the safety of the occupant while traveling, such as a sleeping net and/or a safety belt, as described for example in U.S. Pat.","Nos.","5,536,042 and 5,375,879.Stiff element 213 is configured to support the SAEDP 212 and to resist deformation during a collision in order to reduce compartment intrusion.","Part of the stiff element 213 is located, during normal driving, at eye level between the SAEDP 212 and the outside environment.","Optionally, the stiff element covers, from the outside, more than 80% of the SAEDP on the compartment side walls.","Optionally, the vehicle also includes a crumple zone located at eye level between the stiff element 213 and the outside environment.","In another embodiment, the vehicle includes a pneumatic pad configured to inflate in order to protect the occupant, in addition to the SAEDP 212, against hitting the inner side of the vehicle compartment during a collision.","Optionally, the pneumatic pad is configured to deploy in front of the SAEDP 212 towards the inner side of the compartment.","Alternatively, the pneumatic pad is located between the SAEDP 212 and the stiff element 213, and is configured to deploy behind the SAEDP 212.The pneumatic pad may be mounted to various locations, such as mounted to the front wall, mounted to the rear wall, mounted to the side walls, and/or mounted to the roof.","The camera is configured to take video of the outside environment.","The computer is configured to generate a representation of the outside environment based on the video.","Optionally, the representation is generated from the point of view of the occupant.","The display 215 is configured to present the representation to the occupant.","In one embodiment, the display 215 is comprised in an HMD, and the vehicle further comprises a communication system configured to transmit the representation to the HMD.","In another embodiment, the display 215 is physically coupled to at least one of the SAEDP 212 and the stiff element 213 at eye level of the occupant.","Optionally, the display 215 is a flexible display.","For example, the display 215 may be a flexible display that is based on at least one of the following technologies and their variants: OLED, organic thin film transistors (OTFT), electronic paper (e-paper), rollable display, and flexible AMOLED.","Optionally, the display 215 is flexible enough such that it does not degrade the performance of the SAEDP by more than 20% during a collision.","Having a vehicle compartment that is designed to allow an occupant to lay down comfortably can be done using various compartment designs, which may be different from the designs used in standard vehicles, in which occupants primarily sit up.","In one example, the vehicle does not have an automotive seat with a backrest and safety belt, which enables the occupant to sit straight in the front two thirds of the compartment.","In another example, the vehicle is designed for a single occupant, and the average distance between the mattress and the compartment roof is below 80 cm.","In still another example, the vehicle is designed for a single occupant, and the average distance between the mattress and the compartment roof is below 70 cm.","In still another example, the vehicle is designed for a single occupant, and the average distance of the compartment roof from the road is less than 1 meter.","And in yet another example the vehicle is designed for a single occupant, and the average distance of the compartment roof from the road is less than 80 cm.","It is to be noted that the use of the terms “floor”, “roof”, “side walls”, and “front wall” with respect to the compartment are to be viewed in their common meaning when one considers the compartment to be a mostly convex hull in 3D, such as having a shape that resembles a cuboid.","Thus, for example, an occupant whose face faces forward, will see the front wall ahead, the floor when looking below, the roof when looking above, and a side wall when looking to one of the sides (left or right).","In embodiments that do not resemble cuboids, alternative definitions for these terms may be used based on the relative region (in 3D space) that each of the portions of the compartment occupy.","For example, the floor of the compartment may be considered to be any portion of the compartment which is below at least 80% of the volume of the compartment.","Similarly, the roof may be any portion of the compartment that is above at least 80% of the volume of the compartment.","The front wall may be any portion of the compartment that is ahead of at least 80% of the volume of the compartment, etc.","Note that using this alternative definitions, some portions of the compartment may be characterized as belonging to two different regions (e.g., the front wall and the roof).","Some aspects of this disclosure involve an autonomous on-road vehicle that includes a compartment having a large mirroring element located in front of an occupant who sits in a front seat of the compartment.","Optionally, the mirroring element has height and width exceeding 25×25 cm, such that it covers a square that is at least those dimensions.","Optionally, the mirroring element captures a region corresponding to at least 10×10 degrees, including a region spanning from the horizon to 10° below the horizon, of the occupant's forward field of view during normal driving.","Additionally, the mirroring element provides an effect of reflecting more than 25% of the light arriving from the occupant's direction.","In some embodiments, the vehicle has an advantage that it can increase the perceived compartment volume, which can make travelling in the vehicle more pleasurable for some people.","FIG.","29 illustrates one embodiment of a vehicle having a front mirroring element.","The figure illustrates how the occupant 222 can see her reflection 223 in the mirroring element 220.In one embodiment, the mirroring element 220 is located in front of an occupant who sits in a front seat of the vehicle.","The mirroring element 220 provides an effect of reflecting more than 25% of the light arriving from the occupant's direction.","Optionally, the mirroring element 220 provides an effect of reflecting more than at least one of 50%, 80%, and 90% of the light arriving from the occupant's direction.","Optionally, the mirroring element 220 increases the volume of the vehicle compartment as perceived by the occupant due to the reflection effect.","In one embodiment, the mirroring element 220 has height and width exceeding 25×25 cm, such that it covers a square that is at least those dimensions.","Optionally, the mirroring element 220 captures a region corresponding to at least 10×10 degrees, including a region spanning from the horizon to 10° below the horizon, of the occupant's forward field of view during normal driving.","Optionally, the height and width of the mirroring element 220 is above 50×40 cm, and the mirroring element captures above 30×30 degrees of the occupant's field of view, including a region spanning from the horizon to 30° below the horizon.","Optionally, the mirroring element 220 covers more than 25% of the area where a conventional windshield of a normal non-autonomous on-road vehicle in year 2016 is expected to be located.","The mirroring element 220 may be implemented in different ways, in different embodiments.","In one embodiment, the mirroring element 220 comprises an optical mirror that is essentially flat and perpendicular to the ground.","In this embodiment, most of the effect of reflecting is generated by the optical mirror.","In one example, an optical mirror that is essentially flat and perpendicular to the ground refers to an optical mirror having a radius of curvature greater than a meter and a deviation below ±30° from the perpendicular to the ground.","In another embodiment, the mirroring element 220 comprises a Fresnel type optical reflector comprising many reflecting prisms.","In this embodiment, the Fresnel type optical reflector is not flat, but the reflecting prisms are arranged in angles that reflect the light from the occupant such as to imitate a flat mirror.","In one embodiment, the mirroring element 220 comprises an electronic display that operates based on a camera 221 configured to take video of the occupant 222, and a computer 224 configured to generate a digital representation of the occupant 223 based on the video of the occupant.","In this case, most of the effect of reflecting is generated by light emitted by the electronic display (which is the output of the video of the occupant as generated by the computer 224).","Due to the close proximity between the at least one camera 221 and the occupant, it may be necessary to stitch the reflecting effect of a large area from multiple cameras that capture the occupant from different angles.","In one example, the camera 221 comprises first and second cameras, located to the right and left of the occupant, respectively.","In another example, the camera 221 comprises first and second cameras, located above the level of the occupant's nose and below the level of the occupant's collarbone, respectively, and less than 80 cm away from the occupant.","In still another embodiment, the effect of reflecting is achieved by a digital mirror that comprises multiple cameras embedded within the digital mirror and configured to take images of the occupant, and multiple light emitting pixels configured to emit light rays that generate the effect of reflecting.","In one embodiment, the mirroring element 220 comprises an electronic display, and the vehicle further includes a camera configured to take video of the outside environment in front of the occupant, and a computer configured to generate, based on the video, a representation of the outside environment in front of the occupant at eye level, for displaying on the mirroring element 220.In addition to the effect of reflecting, in some embodiments the mirroring element 220 may also be configured to operate in a second state in which it provides an effect of reflecting less than 20% of the light arriving from the occupant's direction, and to present to the occupant the representation of the outside environment.","Here, presenting the representation may imitate a transparent windshield to the outside environment.","The vehicle may also include, in some embodiments, a display configured to present to the occupant, at eye level in front of the occupant, the representation of the outside environment instead of, or in addition to, the effect of reflecting.","Optionally, the vehicle may include a user interface configured to enable the occupant to switch between seeing the effect of reflecting and seeing the representation of the outside environment.","In one example, the display is comprised in a head-mounted display (HMD).","In another example, the display is mechanically coupled to the compartment, and/or the mirroring element comprises the display.","As described above, the effect of reflecting light that comes from the direction of the occupant may be obtained, in some embodiments, utilizing an HMD.","The following is a more detailed example of such an embodiment.","In one embodiment, an autonomous on-road vehicle includes a compartment comprising a front seat, a camera, a computer, a communication module, and an HMD.","The camera is physically coupled to the vehicle, configured to take images of an occupant who sits in the front seat.","The computer is configured to generate, based on the images, a video that shows a mirror effect.","Herein, the “mirror effect” involves presenting the occupant with an image that is similar to an image that the occupant would see had there been an actual mirror in front of the occupant.","Optionally, the system enables the occupant to have control on the synthetic mirror effect, such as control on the distance between the occupant and her image, and/or control on the width of the image.","The communication module is configured to transmit the video to a head-mounted display (HMD) worn by the occupant, and the HMD is configured to present the video to the occupant, such that the occupant sees a representation of his or her reflection when looking forward at eye level.","Optionally, the HMD is selected from the group comprising: a virtual reality headset, an augmented reality headset, and mixed reality headset.","Optionally, the video presented to the occupant captures at least 30×30 degrees of the occupant's field of view, spanning at least from the horizon to 30° below the horizon.","In one embodiment, the vehicle described above further includes a second camera configured to take a second set of images of the outside environment in front of the occupant.","In this embodiment, the computer is further configured to generate a representation of the outside environment based on the second set of images, and the HMD is configured to present the representation of the outside environment instead of the video that shows the mirror effect or in addition to the video that shows the mirror effect.","In one embodiment, the vehicle described above may include multiple cameras that capture images that are utilized by the computer to generate the video that shows the mirror effect.","In one example, the vehicle comprises at least first and second cameras, which are located to the right and left of the occupant, respectively.","In another example, the vehicle comprises at least first and second cameras, located above the level of the occupant's nose and below the level of the occupant's collarbone, respectively, and which are less than 80 cm away from the occupant.","Some aspects of this disclosure involve utilizing one or more nontransparent side beams in order to help protect the occupant in a case of a collision.","The one or more side beams are stiffer than automotive laminated glass.","In one example, a side beam comprises a high tensile steel pipe and pressed material.","In another example, a side beam comprises an aluminum extruded shape.","In one embodiment, an autonomous on-road vehicle that weighs less than 1500 kg without batteries includes a nontransparent side beam, which is stiffer than automotive laminated glass, and is located during normal driving to the left and at eye level of an occupant who sits in a front seat.","The vehicle also includes a camera configured to take video of the outside environment to the left of the occupant, and a computer configured to generate for the occupant, based on the video, a representation of the outside environment to the left of the occupant at eye level.","Optionally, the representation is presented to the occupant using a display.","In one example, the display is comprised in a head-mounted display (HMD), and the vehicle further comprises a communication system configured to transmit the representation to the HMD.","In another example, the display is coupled to the inner side of the compartment.","The following is a description of an embodiment of a vehicle in which one or more side beams may be utilized to help protect the left side of a vehicle (and an occupant therein).","In one embodiment, an autonomous on-road vehicle includes a nontransparent side beam, a camera (e.g., the camera 161), and a computer (e.g., the computer 143).","Optionally, the vehicle weighs less than 1500 kg without batteries.","The nontransparent side beam, which is stiffer than automotive laminated glass, is located, during normal driving, at eye level to the left of an occupant who sits in a front seat of the vehicle.","Optionally, the side beam is at least 60 cm long and at least 1 cm wide (herein “cm” refers to centimeters).","In one example, the side beam comprises a high tensile steel pipe and pressed material.","In another example, the side beam comprises an aluminum extruded shape.","The camera configured to take video of the outside environment to the left of the occupant.","The computer is configured to generate for the occupant, based on the video, a representation of the outside environment to the left of the occupant at eye level.","Optionally, the representation is generated from the point of view of the occupant, and the vehicle further includes a display configured to present the representation to the occupant.","In one example, the display is comprised in a head-mounted display (HMD), and the vehicle further comprises a communication system configured to transmit the representation to the HMD.","In another example, the display is coupled to the inner side of the compartment.","In some embodiments, a plurality of beams, which may be similar to the side beam described above, may be located in the region of the left side of the vehicle.","It is to be noted that the plurality of beams may not necessarily all have the same dimensions or be made of the same exact materials.","Optionally, the plurality of beams may be connected in various ways in order to form a structure that can better resist compartment deforming in the case of a collision.","For example, in one embodiment, the vehicle includes an additional side beam that is not parallel to the side beam and crosses it to form an “X” shaped structure.","Herein, an “X” shaped structure refers to any structure of two nonparallel beams that cross, and the two do not necessarily form a symmetric “X” (e.g., a symmetric “X” may be obtained when the two beams are of equal length and cross at their centers).","This structure is illustrated in FIG.","30a where beams 231 and 232 cross to form an “X” shape structure.","It is to be noted that the beam 231 is at eye level (i.e., at least a portion of the beam 231 is at the same height as a typical occupant's eyes).","FIG.","30a illustrates one example of a configuration of a plurality of beams located in the left side of the vehicle.","Different designs of vehicles may benefit from utilizing one or more sides beam as described above.","In one embodiment, the side beam is embedded in a movable structure that changes its location with respect to the vehicle compartment.","For example, the side beam may be part of a left door of the vehicle.","In another embodiment, the side beam is embedded in the vehicle compartment itself and does not change its location with respect to the rest of the compartment.","For example, the side beam may be placed in a compartment wall to the left of the occupant.","In order to better protect the occupant from injury due to hitting the head against the side of the vehicle, in some embodiments, the vehicle may comprise a nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) located at eye level between the side beam and the occupant.","The SAEDP is less stiff than a standard automotive glass window.","In one example, the SAEDP comprises a passive material.","In another example, the SAEDP includes an airbag.","And in still another example, the SAEDP includes a pneumatic pad.","Optionally, the vehicle includes a display on which the representation of the outside environment may be presented to the occupant.","Optionally, the display is supported by the SAEDP and/or the side beam.","Optionally, the display is a flexible display.","In a similar fashion to the utilization of beams on the left side of the vehicle, in some embodiments, one or more beams may be used to help protect the occupant's right side.","For example, in one embodiment, the vehicle includes a second side beam, located at eye level to the right of the occupant, and a second camera configured to take video of the outside environment to the right of the occupant.","In this embodiment, the computer is further configured to generate a second representation of the outside environment to the right of the occupant.","Some aspects of this disclosure involve utilizing one or more nontransparent beams in order to help protect the occupant in a case of a collision.","The one or more beams are stiffer than automotive laminated glass.","In one example, a nontransparent beam comprises a high tensile steel pipe and pressed material.","In another example, a nontransparent beam comprises an aluminum extruded shape.","In one embodiment, an autonomous on-road vehicle that weighs less than 1500 kg without batteries includes a nontransparent beam, which is stiffer than automotive laminated glass, and is fixed at eye level in front of an occupant who sits in a front seat of the vehicle during normal driving.","The vehicle also includes a camera configured to take video of the outside environment in front of the occupant, and a computer configured to generate for the occupant, based on the video, a representation of the outside environment in front of the occupant at eye level.","Optionally, the representation is presented to the occupant using a display.","In one example, the display is comprised in a head-mounted display (HMD), and the vehicle further comprises a communication system configured to transmit the representation to the HMD.","In another example, the display is coupled to the inner side of the compartment.","The following is a description of an embodiment of a vehicle in which one or more nontransparent beams may be utilized to help protect the vehicle's front (and an occupant therein).","In one embodiment, an autonomous on-road vehicle includes a nontransparent beam, a camera (e.g., the camera 142), and a computer (e.g., the computer 143).","Optionally, the vehicle weighs less than 1500 kg without batteries.","The nontransparent beam, which is stiffer than automotive laminated glass, is located, during normal driving, at eye level in front an occupant who sits in a front seat of the vehicle.","Optionally, the nontransparent beam is at least 60 cm long and at least 1 cm wide (herein “cm” refers to centimeters).","In one example, the nontransparent beam comprises a high tensile steel pipe and pressed material.","In another example, the nontransparent beam comprises an aluminum extruded shape.","The camera configured to take video of the outside environment in front of the occupant.","The computer is configured to generate for the occupant, based on the video, a representation of the outside environment in front of the occupant at eye level.","Optionally, the representation is generated from the point of view of the occupant, and the vehicle further includes a display configured to present the representation to the occupant.","In one example, the display is comprised in a head-mounted display (HMD), and the vehicle further comprises a communication system configured to transmit the representation to the HMD.","In another example, the display is coupled to the inner side of the compartment.","In some embodiments, a plurality of beams, which may be similar to the nontransparent beam described above, may be located in the front of the vehicle.","It is to be noted that the plurality of beams may not necessarily all have the same dimensions or be made of the same exact materials.","Optionally, the plurality of beams may be connected in various ways in order to form a structure that can better resist compartment deformation in the case of a collision.","For example, in one embodiment, the vehicle includes an additional nontransparent beam that is not parallel to the nontransparent beam and crosses it to form an “X” shaped structure.","This structure is illustrated in FIG.","30b where beams 235 and 236 cross to form an “X” shape structure.","Both of the beams 235 and 236 are at eye level (i.e., at least a portion of each beam is at the same height as a typical occupant's eyes).","FIG.","30b illustrates one example of a configuration of a plurality of beams located in the front of the vehicle.","Different designs of vehicles may benefit from utilizing one or more nontransparent beam as described above.","In one embodiment, the nontransparent beam is embedded in a movable structure that changes its location with respect to the vehicle compartment.","For example, the nontransparent beam may be part of a front door through which the occupant may enter the vehicle.","In another embodiment, the nontransparent beam is embedded in the vehicle compartment itself and does not change its location with respect to the rest of the compartment.","For example, the nontransparent beam may be placed in a compartment wall in front of the occupant.","In order to better protect the occupant from injury (e.g., during a collision), in some embodiments, the vehicle may comprise a nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) located at eye level between the nontransparent beam and the occupant.","The SAEDP is less stiff than a standard automotive glass window.","In one example, the SAEDP comprises a passive material.","In another example, the SAEDP includes an airbag.","And in still another example, the SAEDP includes a pneumatic pad.","Optionally, the vehicle includes a display on which the representation of the outside environment may be presented to the occupant.","Optionally, the display is coupled to the inner side of the compartment.","Optionally, the display is a flexible display.","Various embodiments described herein include a processor and/or a computer.","For example, the autonomous-driving control system may be implemented using a computer and generation of a representation of the outside environment is done using a processor or a computer.","The following are some examples of various types of computers and/or processors that may be utilized in some of the embodiments described herein.","FIG.","31a and FIG.","31b are schematic illustrations of possible embodiments for computers (400, 410) that are able to realize one or more of the embodiments discussed herein.","The computer (400, 410) may be implemented in various ways, such as, but not limited to, a server, a client, a personal computer, a network device, a handheld device (e.g., a smartphone), and/or any other computer form capable of executing a set of computer instructions.","The computer 400 includes one or more of the following components: processor 401, memory 402, computer readable medium 403, user interface 404, communication interface 405, and bus 406.In one example, the processor 401 may include one or more of the following components: a general-purpose processing device, a microprocessor, a central processing unit, a complex instruction set computing (CISC) microprocessor, a reduced instruction set computing (RISC) microprocessor, a very long instruction word (VLIW) microprocessor, a special-purpose processing device, an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), a digital signal processor (DSP), a distributed processing entity, and/or a network processor.","Continuing the example, the memory 402 may include one or more of the following memory components: CPU cache, main memory, read-only memory (ROM), dynamic random access memory (DRAM) such as synchronous DRAM (SDRAM), flash memory, static random access memory (SRAM), and/or a data storage device.","The processor 401 and the one or more memory components may communicate with each other via a bus, such as bus 406.The computer 410 includes one or more of the following components: processor 411, memory 412, and communication interface 413.In one example, the processor 411 may include one or more of the following components: a general-purpose processing device, a microprocessor, a central processing unit, a complex instruction set computing (CISC) microprocessor, a reduced instruction set computing (RISC) microprocessor, a very long instruction word (VLIW) microprocessor, a special-purpose processing device, an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), a digital signal processor (DSP), a distributed processing entity, and/or a network processor.","Continuing the example, the memory 412 may include one or more of the following memory components: CPU cache, main memory, read-only memory (ROM), dynamic random access memory (DRAM) such as synchronous DRAM (SDRAM), flash memory, static random access memory (SRAM), and/or a data storage device Still continuing the examples, the communication interface (405,413) may include one or more components for connecting to one or more of the following: an inter-vehicle network, Ethernet, intranet, the Internet, a fiber communication network, a wired communication network, and/or a wireless communication network.","Optionally, the communication interface (405,413) is used to connect with the network 408.Additionally or alternatively, the communication interface 405 may be used to connect to other networks and/or other communication interfaces.","Still continuing the example, the user interface 404 may include one or more of the following components: (i) an image generation device, such as a video display, an augmented reality system, a virtual reality system, and/or a mixed reality system, (ii) an audio generation device, such as one or more speakers, (iii) an input device, such as a keyboard, a mouse, an electronic pen, a gesture based input device that may be active or passive, and/or a brain-computer interface.","It is to be noted that when a processor (computer) is disclosed in one embodiment, the scope of the embodiment is intended to also cover the use of multiple processors (computers).","Additionally, in some embodiments, a processor and/or computer disclosed in an embodiment may be part of the vehicle, while in other embodiments, the processor and/or computer may be separate of the vehicle.","For example, the processor and/or computer may be in a device carried by the occupant and/or remote of the vehicle (e.g., a server).","As used herein, references to “one embodiment” (and its variations) mean that the feature being referred to may be included in at least one embodiment of the invention.","Moreover, separate references to “one embodiment”, “some embodiments”, “another embodiment”, “still another embodiment”, etc., may refer to the same embodiment, may illustrate different aspects of an embodiment, and/or may refer to different embodiments.","Some embodiments may be described using the verb “indicating”, the adjective “indicative”, and/or using variations thereof.","Herein, sentences in the form of “X is indicative of Y” mean that X includes information correlated with Y, up to the case where X equals Y. Additionally, sentences in the form of “provide/receive an indication indicating whether X happened” refer herein to any indication method, including but not limited to: sending/receiving a signal when X happened and not sending/receiving a signal when X did not happen, not sending/receiving a signal when X happened and sending/receiving a signal when X did not happen, and/or sending/receiving a first signal when X happened and sending/receiving a second signal X did not happen.","Herein, “most” of something is defined herein as above 51% of the something (including 100% of the something).","A “portion” of something refers herein to 0.1% to 100% of the something (including 100% of the something).","Sentences of the form “a portion of an area” refer herein to 0.1% to 100% percent of the area.","As used herein, the terms “comprises,” “comprising,” “includes,” “including,” “has,” “having”, or any other variation thereof, indicate an open claim language that does not exclude additional limitations.","The “a” or “an” is employed to describe one or more, and the singular also includes the plural unless it is obvious that it is meant otherwise.","Certain features of some of the embodiments, which may have been, for clarity, described in the context of separate embodiments, may also be provided in various combinations in a single embodiment.","Conversely, various features of some of the embodiments, which may have been, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-combination.","Embodiments described in conjunction with specific examples are presented by way of example, and not limitation.","Moreover, it is evident that many alternatives, modifications, and variations will be apparent to those skilled in the art.","It is to be understood that other embodiments may be utilized and structural changes may be made without departing from the scope of the appended claims and their equivalents."]],"string":"[\n [\n \"Autonomous vehicle having an external shock-absorbing energy dissipation padding\",\n \"An autonomous on-road vehicle having an outer nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP).\",\n \"In one embodiment, the SAEDP is mounted, during normal driving, to the front side of the vehicle at eye level of an occupant who sits in a front seat of the vehicle.\",\n \"A camera is mounted to the vehicle and takes video of the outside environment in front of the occupant.\",\n \"And a computer generates a representation of the outside environment at eye level for the occupant.\"\n ],\n [\n \"1.An autonomous on-road vehicle having an outer nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP), comprising: an SAEDP mounted, during normal driving, to the front side of the vehicle at eye level of an occupant who sits in a front seat of the vehicle; a camera mounted to the vehicle and configured to take video of the outside environment in front of the occupant; and a computer configured to generate, based on the video, a representation of the outside environment at eye level for the occupant.\",\n \"2.The autonomous on-road vehicle of claim 1, wherein the SAEDP is less stiff than a standard automotive glass window and is designed to absorb some of the crashing energy transmitted to a pedestrian during a pedestrian-vehicle collision.\",\n \"3.The autonomous on-road vehicle of claim 1, wherein the SAEDP comprises a passive material.\",\n \"4.The autonomous on-road vehicle of claim 3, wherein the SAEDP has thickness greater than at least one of the following thicknesses: 1 cm, 2 cm, 5 cm, 10 cm, 15 cm, and 20 cm.\",\n \"5.The autonomous on-road vehicle of claim 1, wherein the SAEDP comprises an automotive airbag configured to inflate in order to protect the pedestrian.\",\n \"6.The autonomous on-road vehicle of claim 5, wherein the airbag has a stowed condition and an inflated condition; the airbag is coupled to an inflator configured to inflate the airbag with gas, and the airbag is located, in the stowed condition, at eye level in front of the occupant; and further comprising an autonomous-driving control system configured to calculate probability of pedestrian-vehicle collision, based on measurements of sensors mounted on the vehicle, and to command the airbag to inflate before the pedestrians head hits the vehicle.\",\n \"7.The autonomous on-road vehicle of claim 1, wherein the SAEDP comprises a pneumatic pad configured to inflate in order to protect the pedestrian, and further comprising an autonomous-driving control system configured to calculate probability of pedestrian-vehicle collision, based on measurements of sensors mounted on the vehicle, and to command the pneumatic pad to start inflate at least 0.5 second before the crash in order to protect the pedestrian.\",\n \"8.The autonomous on-road vehicle of claim 7, wherein the pneumatic pad is reusable.\",\n \"9.The autonomous on-road vehicle of claim 1, wherein the representation is generated from the point of view of the occupant, and further comprising a display configured to present the representation to the occupant.\",\n \"10.An autonomous on-road vehicle having an outer nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP), comprising: an SAEDP stored above or below a windshield located at eye level in front of an occupant who sits in a front seat of the vehicle; a motor configured to move the SAEDP between a first state, in which the SAEDP does not block the occupant's eye level frontal view to the outside environment, and a second state, in which the SAEDP blocks the occupant's eye level frontal view to the outside environment, multiple times without having to be repaired; and a processor configured to receive an indication that a probability of an imminent pedestrian-vehicle collision reaches a threshold, and to command the motor to move the SAEDP from the first state to the second state.\",\n \"11.The autonomous on-road vehicle of claim 10, wherein the SAEDP is less stiff than a standard automotive glass window, and in the second state the SAEDP is configured to absorb some of the crashing energy transmitted to a pedestrian during a pedestrian-vehicle collision.\",\n \"12.The autonomous on-road vehicle of claim 10, wherein the processor is further configured to receive an updated indication that the probability of the imminent pedestrian-vehicle collision does not reach a second threshold, and to command the motor to move the SAEDP to the first state; wherein the second threshold is lower than the threshold, and the processor receives at least one of the indication and the updated indication from an autonomous-driving control system.\",\n \"13.The autonomous on-road vehicle of claim 10, wherein the motor is configured to move the SAEDP over a sliding mechanism, and the processor is configured to command the motor to start moving the SAEDP to the second state at least 0.2 second, 0.5 second, 1 second, or 2 seconds before the pedestrian-vehicle collision in order to protect the pedestrian.\",\n \"14.The autonomous on-road vehicle of claim 10, wherein the SAEDP comprises a pneumatic pad configured to inflate in order to protect the pedestrian.\",\n \"15.The autonomous on-road vehicle of claim 14, wherein the pneumatic pad is reusable, and the processor is configured to command the pneumatic pad to start inflate at least 0.5 second before the pedestrian-vehicle collision.\",\n \"16.The autonomous on-road vehicle of claim 10, wherein the SAEDP comprises a passive material having thickness greater than at least one of the following thicknesses: 1 cm, 2 cm, 5 cm, 10 cm, 15 cm, and 20 cm.\",\n \"17.The autonomous on-road vehicle of claim 10, further comprising a camera configured to take video of the outside environment while the SAEDP is in the second state, a computer configured to generate a representation of the outside environment based on the video, and a display configured to present the representation of the outside environment to the occupant while the SAEDP is in the second state.\",\n \"18.The autonomous on-road vehicle of claim 17, wherein the camera is fixed to the SAEDP, and thus moves with the SAEDP when it is moved between the first and second states.\",\n \"19.The autonomous on-road vehicle of claim 17, wherein the display is fixed to the SAEDP from the inner side, and thus moves with the SAEDP when it is moved between the first and second states; whereby the occupant can watch the display via the windshield when the SAEDP is in the second state.\",\n \"20.The autonomous on-road vehicle of claim 17, wherein the display is at least one of the following displays: a display that is physically coupled to the compartment of the autonomous on-road vehicle, and a display comprised in a head-mounted display.\"\n ],\n [\n \" BACKGROUND Vehicle-pedestrian collisions claim many casualties.\",\n \"This is likely to persist even in the age of autonomous vehicles.\",\n \"In some cases, collisions with pedestrians may be simply impossible to avoid or too dangerous (to the vehicle occupants) to avoid.\",\n \"Vehicle-pedestrian collisions often involve the pedestrian hitting the stiff windshield, which can lead to severe bodily harm to the pedestrian and maybe also to damage the windshield.\",\n \"Thus, there is a need for devices that can reduce the danger in vehicle-pedestrian collisions.\"\n ],\n [\n \" SUMMARY Some aspects of this disclosure involve an autonomous on-road vehicle that includes an outer nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) mounted to the front side of the vehicle during normal driving, such that the SAEDP is in front of and at eye level of an occupant who sits in a front seat of the vehicle.\",\n \"Additionally, the vehicle includes a camera that is mounted to the vehicle and is configured to take video of the outside environment in front of the occupant, and a computer configured to generate, based on the video, a representation of the outside environment at eye level for the occupant.\",\n \"A non-limiting advantage of this vehicle is that it increases the safety of a pedestrian in case of a vehicle-pedestrian collision, without prohibiting the occupant of the vehicle from receiving a frontal view of the outside environment.\",\n \"Another aspect of this disclosure involves an autonomous on-road vehicle having an outer nontransparent SAEDP.\",\n \"The SAEDP is stored above or below a windshield located at eye level in front of an occupant who sits in a front seat of the vehicle.\",\n \"A motor moves the SAEDP between a first state, in which the SAEDP does not block the occupant's eye level frontal view to the outside environment, and a second state, in which the SAEDP blocks the occupant's eye level frontal view to the outside environment, multiple times without having to be repaired.\",\n \"A processor receives an indication that a probability of an imminent pedestrian-vehicle collision reaches a threshold, and commands the motor to move the SAEDP from the first state to the second state.\",\n \"A non-limiting advantage of this vehicle is that it increases the safety of a pedestrian in case of a vehicle-pedestrian collision, while still having an uncovered windshield during normal driving.\"\n ],\n [\n \"CROSS-REFERENCE TO RELATED APPLICATIONS This application is a Continuation-In-Part of U.S. application Ser.\",\n \"No.\",\n \"15/335,404, filed Oct. 26, 2016, which claims priority to U.S.\",\n \"Provisional Patent Application No.\",\n \"62/246,187, filed on 26 Oct. 2015, and U.S.\",\n \"Provisional Patent Application No.\",\n \"62/369,127, filed on 31 Jul.\",\n \"2016.ACKNOWLEDGMENTS Gil Thieberger would like to thank his holy and beloved teacher, Lama Dvora-hla, for her extraordinary teachings and manifestation of wisdom, love, compassion and morality, and for her endless efforts, support, and skills in guiding him and others on their paths to freedom and ultimate happiness.\",\n \"Gil would also like to thank his beloved parents for raising him exactly as they did.\",\n \"BACKGROUND Vehicle-pedestrian collisions claim many casualties.\",\n \"This is likely to persist even in the age of autonomous vehicles.\",\n \"In some cases, collisions with pedestrians may be simply impossible to avoid or too dangerous (to the vehicle occupants) to avoid.\",\n \"Vehicle-pedestrian collisions often involve the pedestrian hitting the stiff windshield, which can lead to severe bodily harm to the pedestrian and maybe also to damage the windshield.\",\n \"Thus, there is a need for devices that can reduce the danger in vehicle-pedestrian collisions.\",\n \"SUMMARY Some aspects of this disclosure involve an autonomous on-road vehicle that includes an outer nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) mounted to the front side of the vehicle during normal driving, such that the SAEDP is in front of and at eye level of an occupant who sits in a front seat of the vehicle.\",\n \"Additionally, the vehicle includes a camera that is mounted to the vehicle and is configured to take video of the outside environment in front of the occupant, and a computer configured to generate, based on the video, a representation of the outside environment at eye level for the occupant.\",\n \"A non-limiting advantage of this vehicle is that it increases the safety of a pedestrian in case of a vehicle-pedestrian collision, without prohibiting the occupant of the vehicle from receiving a frontal view of the outside environment.\",\n \"Another aspect of this disclosure involves an autonomous on-road vehicle having an outer nontransparent SAEDP.\",\n \"The SAEDP is stored above or below a windshield located at eye level in front of an occupant who sits in a front seat of the vehicle.\",\n \"A motor moves the SAEDP between a first state, in which the SAEDP does not block the occupant's eye level frontal view to the outside environment, and a second state, in which the SAEDP blocks the occupant's eye level frontal view to the outside environment, multiple times without having to be repaired.\",\n \"A processor receives an indication that a probability of an imminent pedestrian-vehicle collision reaches a threshold, and commands the motor to move the SAEDP from the first state to the second state.\",\n \"A non-limiting advantage of this vehicle is that it increases the safety of a pedestrian in case of a vehicle-pedestrian collision, while still having an uncovered windshield during normal driving.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS The embodiments are herein described by way of example only, with reference to the accompanying drawings.\",\n \"No attempt is made to show structural details of the embodiments in more detail than is necessary for a fundamental understanding of the embodiments.\",\n \"In the drawings: FIG.\",\n \"1 is a schematic illustration of components of a system configured to combine video see-through (VST) with video-unrelated-to-the-VST (VUR); FIG.\",\n \"2 illustrates an HMD tracking module that measures the position of the HMD relative to the compartment; FIG.\",\n \"3 illustrates a vehicle in which an occupant wears an HMD; FIG.\",\n \"4 illustrates an occupant wearing an HMD and viewing large VUR and smaller VST; FIG.\",\n \"5a illustrates how the VST moves to the upper left when the occupant looks to the bottom right; FIG.\",\n \"5b illustrates how the VST moves to the bottom right when the occupant looks to the upper left; FIG.\",\n \"6 illustrates HMD-video that includes both a non-transparent VST and video that shows the hands of the occupant and the interior of the compartment; FIG.\",\n \"7 illustrates HMD-video that includes both a partially transparent VST and video that shows the hands of the occupant and the interior of the compartment; FIG.\",\n \"8 illustrates HMD-video that includes a VST and partially transparent video that shows the hands of the occupant and the interior of the compartment; FIG.\",\n \"9a illustrates HMD-video that includes a VUR in full FOV, a first window comprising compartment-video (CV) and a second smaller window comprising the VST; FIG.\",\n \"9b illustrates HMD-video that includes VUR in full FOV, a first window comprising the CV and a second partially transparent smaller window comprising the VST; FIG.\",\n \"10a illustrates HMD-video that includes VUR in full FOV, a first window comprising VST and a second smaller window comprising zoom out of the CV; FIG.\",\n \"10b illustrates HMD-video that includes VUR and a partially transparent CV; FIG.\",\n \"11a illustrates a FOV of a vehicle occupant when the occupant wears an HMD that presents HMD-video; FIG.\",\n \"11b illustrates a FOV of a vehicle occupant when the vehicle occupant does not wear an HMD that presents the video, such as when watching an autostereoscopic display; FIG.\",\n \"11c illustrates FOV of a 3D camera that is able to capture sharp images from different focal lengths; FIG.\",\n \"12 is a schematic illustration of components of a system configured to enable an HMD to cooperate with a window light shading module; FIG.\",\n \"13a illustrates a first mode for a shading module where an occupant sees the outside environment through the optical see-through component; FIG.\",\n \"13b illustrates a second mode for a shading module where the occupant sees the outside environment through a VST; FIG.\",\n \"14 illustrates a VST over a curtain; FIG.\",\n \"15 illustrates a light shading module that is unfurled on the inside of the compartment; FIG.\",\n \"16 illustrates a light shading module that is unfurled on the outside of the compartment; FIG.\",\n \"17 is a schematic illustration of components of a video system that may be used to increase awareness of an occupant of a vehicle regarding an imminent SDRS; FIG.\",\n \"18a illustrates presenting VUR to an occupant when there is no indication that an SDRS event is imminent; FIG.\",\n \"18b illustrates presenting VST responsive to receiving an indication that an SDRS event is imminent (a pothole); FIG.\",\n \"18c illustrates presenting VST responsive to receiving an indication that an SDRS event is imminent (a sharp turn); FIG.\",\n \"19a illustrates presenting VUR and VST when there is no indication that an SDRS event is imminent; FIG.\",\n \"19b illustrates presenting a larger VST responsive to receiving an indication that an SDRS event is imminent (a road bump); FIG.\",\n \"19c illustrates presenting a partially transparent VST responsive to receiving an indication that an SDRS event is imminent; FIG.\",\n \"20a illustrates a smart glass shading module when there is no indication that an SDRS event is imminent; FIG.\",\n \"20b illustrates the smart glass shading module when there is an indication that an SDRS event is imminent; FIG.\",\n \"21a and FIG.\",\n \"21b illustrate vehicles with an SAEDP in their compartment were an occupant uses an HMD to receive a representation of the outside environment; FIG.\",\n \"22 illustrates a vehicle with an SAEDP in the vehicle's compartment with displays; FIG.\",\n \"23 illustrates how an SAEDP protects the occupant in a side collision; FIG.\",\n \"24a and FIG.\",\n \"24b illustrate a vehicle with a motor configured to move a nontransparent SAEDP to cover a side window; FIG.\",\n \"25a and FIG.\",\n \"25b illustrate a vehicle with a motor configured to move a front SAEDP between first and second states; FIG.\",\n \"26a illustrates an SAEDP mounted to the front of a vehicle at eye level of an occupant of the vehicle; FIG.\",\n \"26b illustrates an outer SAEDP that includes two air bags; FIG.\",\n \"27a and FIG.\",\n \"27b illustrate a motorized external SAEDP that can move between first and second states multiple times; FIG.\",\n \"28 illustrates a vehicle compartment in which an occupant may lay down; FIG.\",\n \"29 illustrates a vehicle with a front mirror; FIG.\",\n \"30a illustrates one example of a configuration of a plurality of beams located in the left side of the vehicle; FIG.\",\n \"30b illustrates one example of a configuration of a plurality of beams located in the front of the vehicle; and FIG.\",\n \"31a and FIG.\",\n \"31b are schematic illustrations of computers able to realize one or more of the embodiments discussed herein.\",\n \"DETAILED DESCRIPTION The following are definitions of various terms that may be used to describe one or more of the embodiments in this disclosure.\",\n \"The terms “autonomous on-road vehicle” and “autonomous on-road manned vehicle” refer to cars and motorcycles designed to drive on public roadways utilizing automated driving of level 3 and above according to SAE International standard J3016 “Taxonomy and Definitions for Terms Related to On-Road Motor Vehicle Automated Driving Systems”.\",\n \"For example, the autonomous on-road vehicle may be a level 3 vehicle, in which within known, limited environments, drivers can safely turn their attention away from driving tasks; the autonomous on-road vehicle may be a level 4 vehicle, in which the automated system can control the vehicle in all but a few environments; and/or the autonomous on-road vehicle may be a level 5 vehicle, in which no human intervention is required and the automatic system can drive to any location where it is legal to drive.\",\n \"Herein, the terms “autonomous on-road vehicle” and “self-driving on-road vehicle” are equivalent terms that refer to the same.\",\n \"The term “autonomous on-road vehicle” does not include trains, airplanes, boats, and armored fighting vehicles.\",\n \"An autonomous on-road vehicle utilizes an autonomous-driving control system to drive the vehicle.\",\n \"The disclosed embodiments may use any suitable known and/or to be invented autonomous-driving control systems.\",\n \"The following three publications describe various autonomous-driving control systems that may be utilized with the disclosed embodiments: (i) Paden, Brian, et al.\",\n \"“A Survey of Motion Planning and Control Techniques for Self-driving Urban Vehicles.” arXiv preprint arXiv:1604.07446 (2016); (ii) Surden, Harry, and Mary-Anne Williams.\",\n \"“Technological Opacity, Predictability, and Self-Driving Cars.” Predictability, and Self-Driving Cars (Mar.\",\n \"14, 2016) (2016); and (iii) Gonzalez, David, et al.\",\n \"“A Review of Motion Planning Techniques for Automated Vehicles.” IEEE Transactions on Intelligent Transportation Systems 17.4 (2016): 1135-1145.Autonomous-driving control systems usually utilize algorithms such as machine learning, pattern recognition, neural network, machine vision, artificial intelligence, and/or probabilistic logic to calculate on the fly the probability of an imminent collision, or to calculate on the fly values that are indicative of the probability of an imminent collision (from which it is possible to estimate the probability of an imminent collision).\",\n \"The algorithms usually receive as inputs the trajectory of the vehicle, measured locations of at least one nearby vehicle, information about the road, and/or information about environmental conditions.\",\n \"Calculating the probability of an imminent collision is well known in the art, also for human driven vehicles, such as the anticipatory collision system disclosed in U.S. Pat.\",\n \"No.\",\n \"8,041,483 to Breed.\",\n \"In order to calculate whether a Sudden Decrease in Ride Smoothness (SDRS) event is imminent, the autonomous-driving control system may compare parameters describing the state of the vehicle at time t1 with parameters describing the state of the vehicle at time t2 that is shortly after t1.If the change in one or more of the parameters reaches a threshold (such as deceleration above a certain value, change of height in the road above a certain value, and/or an angular acceleration above a certain value) then it may be determined that an SDRS event is imminent.\",\n \"An “occupant” of a vehicle, as the term is used herein refers to a person that is in the vehicle when it drives.\",\n \"The term “occupant” refers to a typical person having a typical shape, such as a 170 cm tall human (herein “cm” refers to centimeters).\",\n \"An occupant may be a driver, having some responsibilities and/or control regarding the driving of the vehicle (e.g., in a vehicle that is not completely autonomous), or may be a passenger.\",\n \"When an embodiment refers to “the occupant of the vehicle”, it may refer to one of the occupants of the vehicle.\",\n \"Stating that a vehicle has an “occupant” should not be interpreted that the vehicle necessarily accommodates only one occupant at a time, unless that is explicitly stated, such as stating that the vehicle is “designed for a single occupant”.\",\n \"Herein, a “seat” may be any structure designed to hold an occupant travelling in the vehicle (e.g., in a sitting and/or reclining position).\",\n \"A “front seat” is a seat that positions an occupant it holds no farther from the front of the vehicle than any other occupants of the vehicle are positioned.\",\n \"Herein, sitting in a seat also refers to sitting on a seat.\",\n \"Sitting in a seat is to be interpreted in this disclosure as occupying the space corresponding the seat, even if the occupant does so by assuming a posture that does not necessarily correspond to sitting.\",\n \"For example, in some vehicles the occupant may be reclined or lying down, and in other vehicles the occupant may be more upright, such as when leaning into the seat in a half standing half seating position similar to leaning into a Locus Seat by Focal Upright LLC.\",\n \"The interchangeable terms “environment outside the vehicle” and “outside environment” refer to the environment outside the vehicle, which includes objects that are not inside the vehicle compartment, such as other vehicles, roads, pedestrians, trees, buildings, mountains, the sky, and outer space.\",\n \"A sensor “mounted to the vehicle” may be connected to any relevant part of the vehicle, whether inside the vehicle, outside the vehicle, to the front, back, top, bottom, and/or to a side of the vehicle.\",\n \"A sensor, as used herein, may also refer to a camera.\",\n \"The term “camera” refers herein to an image-capturing device that takes images of an environment.\",\n \"For example, the camera may be based on at least one of the following sensors: a CCD sensor, a CMOS sensor, a near infrared (NIR) sensor, an infrared sensor (IR), and a device based on active illumination such as a LiDAR.\",\n \"The term “video” refers to a series of images that may be provided in a fixed rate, variable rates, a fixed resolution, and/or dynamic resolutions.\",\n \"The use of a singular “camera” should be interpreted herein as “one or more cameras”.\",\n \"Thus, when embodiments herein are described as including a camera that captures video and/or images of the outside environment in order to generate a representation of the outside environment, the representation may in fact be generated based on images and/or video taken using multiple cameras.\",\n \"Various embodiments described herein involve providing an occupant of the vehicle with representation of the outside environment, generated by a computer and/or processor, based on video taken by a camera.\",\n \"In some embodiments, video from a single camera (e.g., which may be positioned on the exterior of the vehicle at eye level), may be sent to presentation to the occupant by the processor and/or computer following little, if any, processing.\",\n \"In other embodiments, video from a single camera or multiple cameras is processed in various ways, by the computer and/or processor, in order to generate the representation of the outside environment that is presented to the occupant.\",\n \"Methods and systems for stitching live video streams from multiple cameras, stitching live video streams with database objects and/or other video sources, transforming a video stream or a stitched video stream from one point of view to another point of view (such as for generating a representation of the outside environment for an occupant at eye level, or for generating a compartment view for a person standing outside the compartment), tracking the position of an HMD relative to a compartment, and presenting rendered images that are perfectly aligned with the outside world—are all known in the art of computer graphics, video stitching, image registration, and real-time 360° imaging systems.\",\n \"The following publications are just a few examples of reviews and references that describe various ways to perform the video stitching, image registration, tracking, and transformations, which may be utilized by the embodiments disclosed herein: (i) Wang, Xiaogang.\",\n \"“Intelligent multi-camera video surveillance: A review.” Pattern recognition letters 34.1 (2013): 3-19.\",\n \"(ii) Szeliski, Richard.\",\n \"“Image alignment and stitching: A tutorial.” Foundations and Trends® in Computer Graphics and Vision 2.1 (2006): 1-104.\",\n \"(iii) Tanimoto, Masayuki.\",\n \"“FTV: Free-viewpoint television.” Signal Processing: Image Communication 27.6 (2012): 555-570.\",\n \"(iv) Ernst, Johannes M., Hans-Ullrich Doehler, and Sven Schmerwitz.\",\n \"“A concept for a virtual flight deck shown on an HMD.” SPIE Defense+Security.\",\n \"International Society for Optics and Photonics, 2016.\",\n \"(v) Doehler, H-U., Sven Schmerwitz, and Thomas Lueken.\",\n \"“Visual-conformal display format for helicopter guidance.” SPIE Defense+Security.\",\n \"International Society for Optics and Photonics, 2014.\",\n \"(vi) Sanders-Reed, John N., Ken Bernier, and Jeff GUell “Enhanced and synthetic vision system (ESVS) flight demonstration.” SPIE Defense and Security Symposium.\",\n \"International Society for Optics and Photonics, 2008.And (vii) Bailey, Randall E., Kevin J. Shelton, and J. J. Arthur III.\",\n \"“Head-worn displays for NextGen.” SPIE Defense, Security, and Sensing.\",\n \"International Society for Optics and Photonics, 2011.A video that provides “representation of the outside environment” refers to a video that enables the average occupant, who is familiar with the outside environment, to recognize the location of the vehicle in the outside environment from watching the video.\",\n \"In one example, the average occupant is a healthy 30 years old human who is familiar with the outside environment, and the threshold for recognizing a video as a “representation of the outside environment” is at least 20 correct recognitions of the outside environment out of 30 tests.\",\n \"Herein, sentences such as “VST that represents a view of the outside environment from the point of view of the occupant”, or “VST representation of the outside environment, which could have been seen from the point of view of the occupant” refer to a video representing at least a portion of the outside environment, with a deviation of less than ±20 degrees from the occupant's point of view of the outside environment, and zoom in the range of 30% to 300% (assuming the occupant's unaided view is at 100% zoom level).\",\n \"The VST may be generated based on at least one of the following resources: a video of the outside environment that is taken in real-time, a video of the outside environment that was taken in the past and is played/processed according to the trajectory of the vehicle, a database of the outside environment that is utilized for rendering the VST according to the trajectory of the vehicle, and/or a video that is rendered as function of locations of physical objects identified in the outside environment using detection and ranging systems such as RADAR and/or LIDAR.\",\n \"Moreover, the term “video see-through (VST)” covers both direct representations of the outside environment, such as a video of the outside environment, and/or enriched video of the outside environment, such as captured video and/or rendered video of the outside environment presented together with one or more layers of virtual objects, as long as more than 20% of the average vehicle occupants, who are familiar with the outside environment, would be able to determine their location in the outside environment, while the vehicle travels, without using a map, and with a margin of error below 200 meters.\",\n \"However, it is noted that showing a map that indicates the location of the vehicle on the driving path (such as from the start to the destination) is not considered herein as equivalent to the VST, unless the map includes all of the following properties: the map shows images of the path, the images of the path capture at least 5 degrees of the occupant's FOV at eye level, and the images of the path reflect the dynamics of the vehicle and change in a similar manner to a video taken by a camera mounted to the vehicle and directed to the outside environment.\",\n \"Herein, “field of view (FOV) of the occupant to the outside environment” refers to the part of the outside environment that is visible to the occupant of a vehicle at a particular position and orientation in space.\",\n \"In one example, in order for an occupant-tracking module to calculate the FOV to the outside environment of an occupant sitting in a vehicle compartment, the occupant-tracking module determines the position and orientation of the occupant's head.\",\n \"In another example, in order for an occupant-tracking module to calculate the FOV of an occupant sitting in a vehicle compartment, the occupant-tracking module utilizes an eye tracker.\",\n \"It is noted that sentences such as “a three dimensional (3D) video see-through (VST) that represents a view of the outside environment, which could have been seen from the point of view of the occupant had the FOV not been obstructed by at least a portion of the nontransparent element” cover also just one or more portions of the FOV, and are to be interpreted as “a three dimensional (3D) video see-through (VST) that represents a view of at least a portion of the outside environment, which could have been seen from the point of view of the occupant had at least some of the FOV not been obstructed by at least a portion of the nontransparent element”.\",\n \"The term “display” refers herein to any device that provides a human user with visual images (e.g., text, pictures, and/or video).\",\n \"The images provided by the display may be two-dimensional or three-dimensional images.\",\n \"Some non-limiting examples of displays that may be used in embodiments described in this disclosure include: (i) screens and/or video displays of various devices (e.g., televisions, computer monitors, tablets, smartphones, or smartwatches), (ii) headset- or helmet-mounted displays such as augmented-reality systems (e.g., HoloLens), virtual-reality systems (e.g., Oculus rift, HTC Vive, or Samsung GearVR), and mixed-reality systems (e.g., Magic Leap), and (iii) image projection systems that project images on a occupant's retina, such as: Virtual Retinal Displays (VRD) that create images by scanning low power laser light directly onto the retina, or light-field technologies that transmit light rays directly into the eye.\",\n \"Various embodiments may include a reference to elements located at eye level.\",\n \"The “eye level” height is determined according to an average adult occupant for whom the vehicle was designed, who sits straight and looks to the horizon.\",\n \"Sentences in the form of “an element located at eye level of an occupant who sits in a vehicle” refer to the element and not to the occupant.\",\n \"The occupant is used in such sentences in the context of “eye level”, and thus claims containing such sentences do not require the existence of the occupant in order to construct the claim.\",\n \"Sentences such as “SAEDP located at eye level”, “stiff element located at eye level”, and “crumple zone located at eye level” refer to elements that are located at eye level, but may also extended to other levels, such as from sternum level to the roof level, from floor level to eye level, and/or from floor level to roof level.\",\n \"For example, an SAEDP located at an eye level can extend from sternum level to above the occupant's head, such that at least a portion of the SAEDP is located at the eye level.\",\n \"Herein, “normal driving” refers to typical driving conditions, which persist most of the time the vehicle is in motion.\",\n \"During normal driving the probability of a collision is below a threshold that when reached typically involves one or more of the following actions: deployment of safety devices that are not usually deployed (e.g., inflating airbags), taking evasive action to avoid a collision, and warning occupants of the vehicle about an imminent event that may cause a Sudden Decrease in Ride Smoothness (SDRS).\",\n \"A Shock-Absorbing Energy Dissipation Padding (SAEDP) is an element that may be used to cushion impact of a body during a collision or during SDRS events.\",\n \"Various types of SAEDPs may be used in embodiments described herein, such as passive materials, airbags, and pneumatic pads.\",\n \"Some examples of passive materials that may be used for the SAEDP in one or more of the disclosed embodiments include one or more of the following materials: CONFOR® foam by Trelleborg Applied Technology, Styrofoam by The Dow Chemical Company, Micro-Lattice Materials and/or Metallic Microlattices (such as by HRL Laboratories in collaboration with researchers at University of California and Caltech), non-Newtonian energy Absorbing materials (such as D3O® by D3O lab, and DEFLEXION™ by Dow Corning®), Sorbothane® by Sorbothane Incorporated, and padding that includes compression cells and/or shock absorbers of the Xenith LLC type (such as described in U.S. Pat.\",\n \"No.\",\n \"8,950,735 and US patent application num.\",\n \"20100186150), and materials that include rubber such as a sponge rubber.\",\n \"The term “stiff element” refers to a material having stiffness and impact resistance equal or greater than that of glazing materials for use in motor vehicles as defined in the following two standards: (i) “American National Standard for Safety Glazing Materials for Glazing Motor Vehicles and Motor Vehicle Equipment Operating on Land Highways-Safety Standard” ANSI/SAE Z26.1-1996, and (ii) The Society of Automotive Engineers (SAE) Recommended Practice J673, revised April 1993, “Automotive Safety Glasses” (SAE J673, rev.\",\n \"April 93).\",\n \"The term “stiff element” in the context of low speed vehicles refers to a material having stiffness and impact resistance equal or greater than that of glazing materials for use in low speed motor vehicles as defined in Federal Motor Vehicle Safety Standard 205—Glazing Materials (FMVSS 205), from 49 CFR Ch.\",\n \"V (10-1-04 Edition).\",\n \"The stiff element may be transparent (such as automotive laminated glass, or automotive tempered glass) or nontransparent (such as fiber-reinforced polymer, carbon fiber reinforced polymer, steel, or aluminum).\",\n \"Herein, a nontransparent element is defined as an element having Visible Light Transmittance (VLT) between 0% and 20%, which does not enable the occupant to recognize what lies on the other side of it.\",\n \"For example, a thick ground glass usually allows light to pass through it but does not let the occupant recognize the objects on the other side of it, unlike plain tinted glass that usually lets the occupant recognize the objects on the other side of it, even when it features VLT below 10%.\",\n \"The nontransparent element includes an opaque element having VLT of essentially 0% and includes a translucent element having VLT below 20%.\",\n \"VLT is defined as the amount of incident visible light that passes through the nontransparent element, where incident light is defined as the light that strikes the nontransparent element.\",\n \"VLT is also known as Luminous Transmittance of a lens, a light diffuser, or the like, and is defined herein as the ratio of the total transmitted light to the total incident light.\",\n \"The common clear vehicle windshield has a VLT of approximately 85%, although US Federal Motor Vehicle Safety Standard No.\",\n \"205 allows the VLT to be as low as 70%.\",\n \"Sentences such as “video unrelated to the VST (VUR)” mean that an average occupant would not recognize the video as a representation of the outside environment.\",\n \"In some embodiments, the content of the VUR does not change as function of the position of the occupant's head, which means that the point of view from which the occupant watches the VUR does not change essentially when the occupant's head moves.\",\n \"Herein, stabilization effects, image focusing, dynamic resolution, color corrections, and insignificant changes to less than 10% of the frame as function of the position of the occupant's head—are still considered as content that does not change as function of the position of the occupant's head.\",\n \"Examples of such content (common in the year 2016) include cinema movies, broadcast TV shows, standard web browsers, and Microsoft Office 2016 applications (such as Word, Excel and PowerPoint).\",\n \"Herein, a “crumple zone” refers to a structure designed to slow down inertia and absorb energy from impact during a traffic collision by controlled deformation.\",\n \"The controlled deformation absorbs some of the impact within the outer parts of the vehicle, rather than being directly transferred to the occupants, while also preventing intrusion into and/or deformation of the compartment.\",\n \"Crumple zone may be achieved by various configurations, such as one or more of the following exemplary configurations: (i) by controlled weakening of sacrificial outer parts of the vehicle, while strengthening and increasing the stiffness of the inner parts of the vehicle, such as by using more reinforcing beams and/or higher strength steels for the compartment; (ii) by mounting composite fiber honeycomb or carbon fiber honeycomb outside the compartment; (iii) by mounting an energy absorbing foam outside the compartment; and/or (iv) by mounting an impact attenuator that dissipates impact.\",\n \"In order to enable an occupant of a vehicle to view the outside environment, without needing to look out of a physical window, some aspects of this disclosure involve systems that combine video see-through (VST) with video-unrelated-to-the-VST (VUR).\",\n \"In one embodiment, a system configured to combine video see-through (VST) with video-unrelated-to-the-VST (VUR) includes a head-mounted display (HMD), a camera, an HMD tracking module and a computer.\",\n \"The HMD is configured to be worn by an occupant of a compartment of a moving vehicle and to present an HMD-video to the occupant.\",\n \"The camera, which is mounted to the vehicle, is configured to take video of the outside environment (Vout).\",\n \"The HMD tracking module is configured to calculate position of the HMD relative to the compartment, based on measurements of a sensor.\",\n \"The computer is configured to receive a location of a video see-through window (VSTW) in relation to the compartment, and to calculate, based on the position of the HMD relative to the compartment, a window-location for the VSTW on the HMD-video.\",\n \"Additionally, the computer is further configured to generate, based on the window-location and the Vout, the VST that represents a view of the outside environment from the point of view of the occupant.\",\n \"The computer is also configured to generate the HMD-video based on combining the VUR with the VST in the window-location.\",\n \"It is to be noted that the content of the VUR is unrelated to the video taken by the camera.\",\n \"In one embodiment, a system configured to combine video see-through (VST) with video-unrelated-to-the-VST (VUR) includes at least the following components: a head-mounted display (HMD), such as HMD 15, a camera (e.g., camera 12), an HMD tracking module 27, and a computer 13.FIG.\",\n \"1 provides a schematic illustration of at least some of the relationships between the components mentioned above.\",\n \"The HMD 15 is configured to be worn by an occupant of a compartment of a moving vehicle and to present an HMD-video 16 to the occupant.\",\n \"In one embodiment, the HMD 15 is an augmented-reality (AR) HMD.\",\n \"In another embodiment, the HMD 15 is a virtual reality (VR) HMD.\",\n \"Optionally, in this embodiment, the system further comprises a video camera mounted to the VR HMD, and the VST video comprises video of the compartment received from the video camera mounted to the VR HMD.\",\n \"In yet another embodiment, the HMD 15 is a mixed reality HMD.\",\n \"The term “Mixed Reality” (MR) as used herein involves a system that is able to combine real world data with virtual data.\",\n \"Mixed Reality encompasses Augmented Reality and encompasses Virtual Reality that does not immerse its user 100% of the time in the virtual world.\",\n \"Examples of mixed reality HMDs include, but are not limited to, Microsoft HoloLens HMD and MagicLeap HMD.\",\n \"The camera 12, which is mounted to the vehicle, is configured to take video of the outside environment (Vout).\",\n \"Optionally, the data captured by the camera comprises 3D data.\",\n \"For example, the camera may be based on at least one of the following sensors: a CCD sensor, a CMOS sensor, a near infrared (NIR) sensor, an infrared sensor (IR), and a device based on active illumination such as a LiDAR.\",\n \"The HMD tracking module 27 is configured to calculate position of the HMD 15 relative to the compartment, based on measurements of a sensor.\",\n \"In different embodiments, the HMD tracking module 27 may have different configurations.\",\n \"In one embodiment, the sensor comprises first and second Inertial Measurement Units (IMUs).\",\n \"In this embodiment, the first IMU is physically coupled to the HMD 15 and is configured to measure a position of the HMD 15, and the second IMU is physically coupled to the compartment and is configured to measure a position of the compartment.\",\n \"The HMD tracking module 27 is configured to calculate the position of the HMD 15 in relation to the compartment based on the measurements of the first and second IMUs.\",\n \"In another embodiment, the sensor comprises an Inertial Measurement Unit (IMU) and a location measurement system.\",\n \"In this embodiment, the IMU is physically coupled to the HMD 15 and is configured to measure an orientation of the HMD 15.The location measurement system is physically coupled to the compartment and is configured to measure a location of the HMD in relation to the compartment.\",\n \"The HMD tracking module 27 is configured to calculate the position of the HMD 15 in relation to the compartment based on the measurements of the IMU and the location measurement system.\",\n \"Optionally, the location measurement system measures the location of the HMD 15 in relation to the compartment based on at least one of the following inputs: a video received from a camera that captures the HMD 15, a video received from a stereo vision system, measurements of magnetic fields inside the compartment, wireless triangulation measurements, acoustic positioning measurements, and measurements of an indoor positioning systems.\",\n \"FIG.\",\n \"2 illustrates one embodiment in which the HMD tracking module 27 is physically coupled to the compartment and is configured to measure the position of the HMD relative to the compartment.\",\n \"The HMD tracking module 27 may utilize a passive camera system, an active camera system that captures reflections of a projected grid, and/or a real-time locating systems based on microwaves and/or radio waves.\",\n \"The computer 13 is configured to receive a location of a video see-through window (VSTW) in relation to the compartment, and to calculate, based on the position of the HMD relative to the compartment, a window-location for the VSTW on the HMD-video.\",\n \"The computer 13 is also configured to generate, based on the window-location and the Vout, the VST that represents a view of the outside environment from the point of view of the occupant.\",\n \"Optionally, the VST is rendered as a 3D video content.\",\n \"Additionally, the computer 13 is further configured to generate the HMD-video 16 based on combining the VUR with the VST in the window-location.\",\n \"The computer 13 may use various know in the art computer graphics functions and/or libraries to generate the VST, transform the VST to the occupant's point of view, render the 3D video content, and/or combine the VUR with the VST.\",\n \"In one embodiment, the content of the VUR does not change when the occupant moves the head, and the content of the VUR is unrelated to the video taken by the camera.\",\n \"Additionally, the content of the VUR is generated based on data that was received more than 2 seconds before the HMD-video 16 is displayed to the occupant.\",\n \"Some examples of the VUR include a video stream of at least one of the following types of content: a recorded television show, a computer game, an e-mail, and a virtual computer desktop.\",\n \"FIG.\",\n \"3 illustrates one embodiment in which the occupant 14 wears an HMD 15.The HMD 15 provides video to the occupant 14 through the display of the HMD 15.The vehicle includes a camera 12 that takes video of the outside environment 11a and processes it in a manner suitable for the location of the occupant.\",\n \"The processed video is provided to the occupant's display in the HMD 15 as a VSTW and the position of the VSTW is calculated in relation to the compartment of the vehicle and moves with the compartment.\",\n \"While the vehicle is in motion, the VSTW change its content to represent the outside environment 11a of the vehicle.\",\n \"Whereas the video-unrelated-to-the-VST doesn't change when the occupant moves his head.\",\n \"The computer is configured to receive a location of a VSTW in relation to the compartment, and to calculate, based on the position of the occupant's head, a window-location for the VSTW on the video.\",\n \"FIG.\",\n \"4 illustrates one embodiment in which the occupant 44 wears HMD 45 and views large VUR 40 and smaller VST 41a.\",\n \"The VUR 40 does not change when the occupant's head 44 moves.\",\n \"The VSTW presents video of the street based on video taken by the camera that is mounted to the vehicle.\",\n \"The location of the video-see-through window in relation to the compartment does not change when the occupant 44 moves his/her head in order to imitate a physical window that does not change its position relative to the compartment when the occupant's head moves.\",\n \"FIG.\",\n \"5a illustrates how, in one embodiment, the VST moves to the upper left when the occupant 44 looks to the bottom right.\",\n \"FIG.\",\n \"5b illustrates how the VST moves to the bottom right when the occupant 44 looks to the upper left, while the VUR moves with the head.\",\n \"In both cases, the VUR moves with the head while the location of the VST changes according to the movement of the head relative to the compartment as measured by the HMD tracking module 27.In some embodiments, the content of the VUR may be augmented-reality content, mixed-reality content, and/or virtual-reality content rendered to correspond to the occupant's viewing direction.\",\n \"In this embodiment, the VUR is unrelated to the video taken by the camera.\",\n \"In one example, the VUR may include a video description of a virtual world in which the occupant may be playing a game (e.g., represented by an avatar).\",\n \"Optionally, in this example, most of the features of the virtual world are different from the view of the outside of the vehicle (as seen from the occupant's viewing direction).\",\n \"For example, the occupant may be driving in a city, while the virtual world displays woods, a meadow, or outer space.\",\n \"In another example, the VUR may include augmented reality content overlaid above a view of the inside of the compartment.\",\n \"In addition to the components described above, in some embodiments, the system may include a second camera that is mounted to the HMD and is configured to take video of the compartment (Vcomp).\",\n \"In this embodiment, the computer is further configured to generate a compartment-video (CV), based on Vcomp and a location of a compartment-video window (CVW) in relation to the HMD-video (e.g., HMD-video 16), and to generate the HMD-video also based on the CV in the CVW, such that the HMD-video combines the VUR with the VST in the window-location and with the CV in the CVW.\",\n \"There are various ways in which the CVW may be incorporated into the HMD-video.\",\n \"Some examples of these approaches are illustrated in the following figures.\",\n \"FIG.\",\n \"6 illustrates HMD-video that includes both a non-transparent VST 55 in the window-location and a CV 56 that shows the hands of the occupant and the interior of the compartment in the CVW.\",\n \"FIG.\",\n \"7 illustrates HMD-video that includes both a partially transparent VST 57 in the window-location and the CV 56 that shows the hands of the occupant and the interior of the compartment in the CVW.\",\n \"FIG.\",\n \"8 illustrates HMD-video that includes a VST 58 and partially transparent CV 59.The figure illustrates that the occupant sees the outside environment in full field-of-view (FOV), while on top of it there is a partially transparent image (illustrated as dotted image) of the compartment and the hands of the occupant, in order to help the occupant not to hit things in the compartment.\",\n \"FIG.\",\n \"9a illustrates HMD-video that includes a VUR 70 in full FOV, a first window comprising the CV 71 in the CVW and a second smaller window comprising the VST 72 in the window-location.\",\n \"FIG.\",\n \"9b illustrates HMD-video that includes VUR 70 in full FOV, a first window comprising the CV 71 in the CVW and a second partially transparent smaller window comprising the VST 73 in the window-location.\",\n \"FIG.\",\n \"10a illustrates HMD-video that includes VUR 70 in full FOV, a first window comprising VST 75 in the window-location and a second smaller window comprising zoom out of the CV 76 in the CVW.\",\n \"Optionally, the cabin view in the zoom out is smaller than in reality, and may enable the occupant to orient in the cabin.\",\n \"Optionally, the occupant may move the CVW, as illustrated in FIG.\",\n \"10a where the zoom out of the CV in the CVW is somewhat above its location in reality.\",\n \"FIG.\",\n \"10b illustrates HMD-video that includes VUR 70 and a partially transparent CV 72.Here a first occupant sees the VUR in full field-of-view (FOV), and on top of it there is a partially transparent image of the compartment and a second occupant that sits to the left of the first occupant, which may help the first occupant not to hit the second occupant.\",\n \"There may be various ways in which the system determines the location and/or size of the VSTW.\",\n \"In one embodiment, the VSTW is pinned to at least one of the following locations: a specific physical location and a location of an object in the compartment, such that the location of the VSTW in relation to the compartment does not change when the occupant moves his/her head with the HMD 15 as part of watching the HMD-video 16 and without commanding the VSTW to move in relation to the compartment.\",\n \"In another embodiment, the system includes a user interface configured to receive a command from the occupant to move and/or resize the VSTW in relation to the compartment.\",\n \"In one example, the command is issued through a voice command (e.g., saying “move VST to the bottom”).\",\n \"In another example, the command may be issued by making a gesture, which is detected by a gesture control module in the compartment and/or on a device of the occupant (e.g., as part of the HMD).\",\n \"Optionally, in this embodiment, the computer is further configured to: update the window-location based on the command from the occupant, and generate an updated VST based on the updated window-location and the video taken by the camera.\",\n \"In this embodiment, the VST and the updated VST present different VSTW locations and/or dimensions in relation to the compartment.\",\n \"Optionally, the HMD is configured not to present any part of the VST to the occupant when the window-location is not in the field of view presented to the occupant through the HMD.\",\n \"In yet another embodiment, the system may further include a video analyzer configured to identify an Object Of Interest (OOI) in the outside environment.\",\n \"For example, the OOI of interest may be a certain landmark (e.g., a building), a certain object (e.g., a store or a certain model of automobile), or a person.\",\n \"In this embodiment, the computer is further configured to receive, from the video analyzer, an indication of the position of the OOI, and to track the OOI by adjusting the window-location according to the movements of the vehicle, such that the OOI is visible via the VST.\",\n \"Optionally, the HMD is configured not to present any part of the VST to the occupant when the window-location is not in the field of view presented to the occupant through the HMD.\",\n \"The VST that represents the view of the outside environment from the point of view of the occupant, in some embodiments, does not necessarily match the video taken by the cameras.\",\n \"In one embodiment, the VST may utilize image enhancement techniques to compensate for outside lighting conditions, to give an occupant an experience similar to looking out through a conventional vehicle window but without the view being distorted by raindrops or dirt on the window, and/or to improve the visual impression of the outside environment e.g.\",\n \"by showing background images which are different from those retrievable from the outside environment.\",\n \"Additionally or alternatively, the VST may mimic the outside environment, alter the outside environment, and/or be completely different from what can be seen on the outside environment.\",\n \"The VST may be focused on providing visual information that makes the travelling more fun.\",\n \"The vehicle may provide different styles of the outside environment to different occupants in the vehicle, such that a first VST provided to a first occupant may mimic the outside environment, while a second VST provided to a second occupant may alter the outside environment and/or be completely different from the outside environment, optionally for comfort enhancement and/or entertainment.\",\n \"In some embodiments, the VST is informative, and aids at least some of the occupants to determine the location of the vehicle in the environment.\",\n \"In one embodiment, at least some of those occupants could not determine their location without the VST.\",\n \"In one example, less than 20% of average vehicle occupants, who are familiar with the outside environment, are able to determine their real location in the outside environment by watching the VUR, without using a map, with a margin of error that is less than 100 meters, and while the vehicle travels; while more than 20% of the average vehicle occupants, who are familiar with the outside environment, are able to determine their real location in the outside environment by watching the VST, without using a map, and with a margin of error that is less than 100 meters, and while the vehicle travels.\",\n \"FIG.\",\n \"11a illustrates a FOV in the context of presented video and terminology used herein.\",\n \"The vehicle occupant 200 wears an HMD 201 that presents HMD-video (such as HMD-video 16).\",\n \"The HMD-video may be presented at a single focal plane, or at multiple focal planes, depending on the characteristics of the HMD 201 (when the occupant focuses on a certain focal plane, then his/her point of gaze is said to be on the certain focal plane).\",\n \"In addition, the presented objects may be two-dimensional (2D) virtual objects and/or three-dimensional (3D) virtual objects that may also be referred to as holographic objects.\",\n \"Element 204 represents the location of a nontransparent element fixed to the vehicle compartment.\",\n \"In one example, the HMD 201 is a holographic HMD, such as Microsoft HoloLens, which can present content displayed on a series of focal planes that are separated by some distance.\",\n \"The virtual objects may be presented before the nontransparent element (e.g., polygons 202, 203), essentially on the nontransparent element 204, and/or beyond the nontransparent element (e.g., polygons 205, 206).\",\n \"As a result, the occupant's gaze distance may be shorter than the distance to the nontransparent element (e.g., distance to polygons 202, 203), essentially equal to the distance to the nontransparent element 204, and/or longer than the distance to the nontransparent element (e.g., distance to polygons 205, 206).\",\n \"Polygon 207 represents a portion of the presented video at eye level of the vehicle occupant, which in one example is within ±7 degrees from the horizontal line of sight.\",\n \"Although the figure illustrates overlapping FOVs of polygons 202, 203, 204, and 205, the HMD may show different objects, capturing different FOVs, at different focal planes.\",\n \"In one example, the HMD may project an image throughout a portion of, or all of, a display volume.\",\n \"Further, a single object such as a vehicle could occupy multiple volumes of space.\",\n \"According to the terminology used herein, the nontransparent element 204 is said to be located on FOV overlapping the FOV of polygons 205 and 203 because polygons 203, 204, 205 share the same FOV.\",\n \"FOV of polygon 206 is contained in the FOV of polygon 204, and FOV of polygon 207 intersects the FOV of polygon 204.FOV of polygon 203 is before the nontransparent element 204 and therefore may hide the nontransparent element 204 partially or entirely, especially when utilizing a multi-focal plane HMD.\",\n \"FIG.\",\n \"11b illustrates a FOV in the context of the presented video, where the vehicle occupant 210 does not wear an HMD that presents the video, such as when watching an autostereoscopic display.\",\n \"The autostereoscopic display is physically located on plane 214 and the presented video may be presented at a single focal plane, or at multiple focal planes, depending on the characteristics of the autostereoscopic display.\",\n \"In one example, the autostereoscopic display is a holographic display, such as SeeReal Technologies holographic display, where the presented video may present virtual objects before the focal plane of the autostereoscopic display (e.g., planes 212, 213), essentially on the focal plane of the autostereoscopic display 214, and/or beyond the focal plane of the autostereoscopic display (e.g., planes 215, 216).\",\n \"As a result, the occupant's gaze distance may be shorter than the distance to the autostereoscopic display (e.g., planes 212, 213), essentially equal to the distance to the autostereoscopic display 214, and/or longer than the distance to the autostereoscopic display (e.g., planes 215, 216).\",\n \"The term “autostereoscopic” includes technologies such as automultiscopic, glasses-free 3D, glassesless 3D, parallax barrier, integral photography, lenticular arrays, Compressive Light Field Displays, holographic display based on eye tracking, color filter pattern autostereoscopic display, volumetric display that reconstructs light field, integral imaging that uses a fly's-eye lens array, and/or High-Rank 3D (HR3D).\",\n \"FIG.\",\n \"11c illustrates FOV of a 3D camera that is able to capture sharp images from different focal lengths.\",\n \"In some embodiments, the vehicle and/or the HMD utilize at least one Inertial Measurement Unit (IMU), and the system utilizes an Inertial Navigation System (INS) to compensate imperfections in the IMU measurements.\",\n \"An INS typically has one or more secondary navigation sensors that provide direct measurements of the linear velocity, position and/or orientation of the vehicle.\",\n \"These secondary navigation sensors could be anything from stereo vision systems, to GPS receivers, to digital magnetic compasses (DMCs) or any other type of sensor that could be used to measure linear velocity, position and/or orientation.\",\n \"In one example, the information from these secondary navigation sensors is incorporated into the INS using an Extended Kalman Filter (EKF).\",\n \"The EKF produces corrections that are used to adjust the initial estimations of linear velocity, position and orientation that are calculated from the imperfect IMU measurements.\",\n \"Adding secondary navigation sensors into an INS can increase its ability to produce accurate estimations of the linear velocity, position and orientation of the vehicle over long periods of time.\",\n \"In one embodiment, the system utilizes domain specific assumptions in order to reduce drift of an INS used to calculate the HMD spatial position in relation to the compartment.\",\n \"More specifically, the following methods may be used to reduce or correct drift.\",\n \"Such methods generally fall in the categories of using sensor fusion and/or domain specific assumptions.\",\n \"(i) Sensor fusion refers to processes in which signals from two or more types of sensors are used to update and/or maintain the state of a system.\",\n \"In the case of INS, the state generally includes the orientation, velocity and displacement of the device measured in a global frame of reference.\",\n \"A sensor fusion algorithm may maintain this state using IMU accelerometer and gyroscope signals together with signals from additional sensors or sensor systems.\",\n \"There are many techniques to perform sensor fusion, such as Kalman filter and particle filter.\",\n \"One example of periodically correcting drift is to use position data from a triangulation positioning system relative to the compartment.\",\n \"Such systems try to combine the drift free nature of positions obtained from the triangulation positioning system with the high sampling frequency of the accelerometers and gyroscopes of the IMU.\",\n \"Roughly speaking, the accelerometer and gyroscope signals are used to ‘fill in the gaps’ between successive updates from the triangulation positioning system.\",\n \"Another example of reducing the drift is using a vector magnetometer that measures magnetic field strength in a given direction.\",\n \"The IMU may contain three orthogonal magnetometers in addition to the orthogonal gyroscopes and accelerometers.\",\n \"The magnetometers measure the strength and direction of the local magnetic field, allowing the north direction to be found.\",\n \"(ii) In some embodiments, it is possible to make domain specific assumptions about the movements of the occupant and/or the vehicle.\",\n \"Such assumptions can be used to minimize drift.\",\n \"One example in which domain specific assumptions may be exploited is the assumption that when the vehicle accelerates or decelerates significantly, the HMD accelerates or decelerates essentially the same as the vehicle, allowing HMD drift in velocity to be periodically corrected based on a more accurate velocity received from the autonomous-driving control system of the vehicle.\",\n \"Another example in which domain specific assumptions may be exploited is the assumption that when the vehicle accelerates or decelerates significantly, the HMDs of two occupants travelling in the same vehicle accelerate or decelerate essentially the same, allowing HMD drifts to be periodically corrected based on comparing the readings of the two HMDs.\",\n \"Still another example in which domain specific assumptions are exploited is the assumption that the possible movement of an HMD of a belted occupant is most of the time limited to a portion of the compartment, allowing HMD drifts to be periodically corrected based on identifying when the HMD exceeds beyond that portion of the compartment.\",\n \"In one example, it may be desirable to adjust the position of displaying a virtual object in response to relative motion between the vehicle and the HMD so that the virtual object would appear stationary in location.\",\n \"However, the HMD IMU may indicate that the HMD is moving even when the detected motion is a motion of the vehicle carrying the HMD.\",\n \"In order to distinguish between motion of the HMD caused by the vehicle and motion of the HMD relative to the vehicle, non-HMD sensor data may be obtained by the HMD from sensor such as an IMU located in the vehicle and/or the GPS system of the vehicle, and the motion of the vehicle may be subtracted from the motion of the HMD in order to obtain a representation of the motion of the HMD relative to the vehicle.\",\n \"By differentiating movements of the HMD caused by the occupant motion compared to movements caused by the vehicle motion, the rendering of the virtual object may be adjusted for the relative motion between the HMD and the vehicle.\",\n \"Using the nontransparent element, instead of a transparent glass window that provides the same FOV to the outside environment, may provide various benefits, such as: (i) reduced manufacturing cost of the vehicle compared to a similar vehicle having instead of the nontransparent element a transparent glass window that provides the same FOV to the outside environment as provided by the 3D display device, (ii) reduced weight of the vehicle compared to a similar vehicle having instead of the nontransparent element a transparent glass window that provides the same FOV to the outside environment as provided by the 3D display device, and provides the same safety level, (iii) better aerodynamic shape and lower drag for the vehicle, which results in an improved energy consumption, and (iv) improved privacy for the occupant as a result of not enabling an unauthorized person standing nearby the vehicle to see the occupant directly.\",\n \"The term “real-depth VST window (VSTW)” is defined herein as an imaging display that shows a 3D image of an outside environment located beyond a wall that interrupts the occupant's unaided view of the outside environment.\",\n \"The real-depth VSTW has the following characteristics: (i) the 3D image corresponds to a FOV to the outside environment beyond the wall, as would have essentially been seen by the occupant had the wall been removed; (ii) the outside environment is captured by a camera, and the rendering of the 3D image is based on images taken by the camera; and (iii) while looking via the imaging display, the occupant's point of gaze (where one is looking) is most of the time beyond the wall that interrupts the occupant's unaided view of the outside environment.\",\n \"A possible test to determine whether “(i) the 3D image corresponds to a FOV to the outside environment beyond the wall, as would have essentially been seen by the occupant had the wall been removed” is whether an imaginary user standing beyond the wall, watching both the real-depth VSTW and the outside environment, would recognize that at least 20% of the contours of objects in the 3D image correspond to the contours of the objects seen on the outside environment.\",\n \"Differences between the colors of the corresponding objects in the 3D image and the outside environment usually do not affect the criterion of the 20% corresponding contours, as long as the color difference does not affect the perception of the type of object.\",\n \"For example, different skin colors to corresponding people in the 3D image and the outside environment do not violate the criterion of the 20% corresponding contours.\",\n \"As another example, differences in the weight and/or height of corresponding objects in the 3D image and the outside environment do not violate the criterion of the 20% corresponding contours as long as the imaginary user understands that the objects correspond to the same person.\",\n \"Sentences such as “from the FOV of the occupant” are to be interpreted as no more than 20 degrees angular deviation from the field of view of the occupant to the outside environment.\",\n \"Zoom in/out does not affect the FOV as long as the average occupant would still recognize the rendered environment as the 3D VST.\",\n \"For example, zoom in of up to ×4, which maintains no more than 20 degrees angular deviation from the FOV of the occupant to the outside environment, is still considered “from the FOV of the occupant”.\",\n \"Reasonable lateral deviation essentially does not affect the FOV as long as the average occupant would still recognize the rendered environment as the 3D VST.\",\n \"For example, displaying to the occupant the outside environment from the FOV of a camera located on the roof of the occupant's vehicle, is still considered as showing the outside environment from the occupant's FOV.\",\n \"A possible test to determine whether “(ii) the outside environment is measured by a camera, and the images taken by the camera are used to render the 3D image” is whether the real-depth VSTW would display a different 3D VST when it does not receive the images taken by the camera.\",\n \"For example, assuming the camera is a 3D video camera, and the 3D image is a manipulation of the images taken by the 3D video camera; then, when the real-depth VSTW does not receive the images, it cannot show the changes that are taking place in the outside environment.\",\n \"As another example, assuming the 3D image is mainly rendered from cached data stored in a database, and the camera is used to provide the setup of objects that behave in an unknown way, such as trajectories of nearby vehicles on the road, or a gesture of a person walking beyond the wall; then, when the output of the camera is used to render the 3D image, the real-depth VSTW would represent the unknown trajectory of the nearby vehicles or the unknown gesture of the person, while when the output of the camera is not used to render the 3D image, the real-depth VSTW would not represent the unknown trajectory of the nearby vehicles or the unknown gesture of the person merely because the renderer does not have that data.\",\n \"A possible test to determine whether “(iii) the occupant's point of gaze (where one is looking) is most of the time beyond the wall that interrupts the occupant's unaided view of the outside environment” includes the following steps: (a) use eye tracker to determine the point of gaze on a representative scenario, (b) measure the distance to the wall, and (c) determine whether the average gaze distance is longer than the distance to the wall.\",\n \"Some aspects of this disclosure involve a system that utilizes window shading of a vehicle window in order to improve the quality of video viewed by an occupant of the vehicle who wears a head-mounted display (HMD).\",\n \"In one embodiment, an autonomous on-road vehicle includes a system configured to enable an HMD to cooperate with a window light shading module.\",\n \"This embodiment involves a light shading module, a camera, a processor, and the HMD.\",\n \"The light shading module is integrated with a vehicle window and is configured to be in at least one of first and second states.\",\n \"In the first state the Visible Light Transmittance (VLT) of the vehicle window is above 10% of ambient light entering through the window, in the second state the VLT of the vehicle window is below 50% of ambient light entering through the window, and the VLT of the vehicle window in the first state is higher than the VLT of the vehicle window in the second state.\",\n \"The camera is fixed to the vehicle and configured to take video of the outside environment.\",\n \"The processor is configured to generate, based on the video, a video see-through (VST) that represents the outside environment from a point of view of an occupant looking to the outside environment through at least a portion of the vehicle window.\",\n \"The HMD comprises an optical see-through component and a display component; the HMD is configured to operate according to a first mode of operation when the occupant looks at the direction of the vehicle window and the light shading module is in the first state, and to operate according to a second mode of operation when the occupant looks at the direction of the vehicle window and the light shading module is in the second state.\",\n \"Wherein the total intensity of the VST light, emitted by the display component and reaching the occupant's eyes, is higher in the second mode than in the first mode.\",\n \"In one embodiment, a system configured to enable a head-mounted display (HMD) to cooperate with a window light shading module of an autonomous on-road vehicle includes at least the following elements: the HMD 62, a light shading module 61, a camera (such as camera 12), and a processor 18.FIG.\",\n \"12 is a schematic illustration of at least some of the relationships between the system elements mentioned above.\",\n \"The light shading module 61 is integrated with a vehicle window and is configured to be in at least one of first and second states.\",\n \"Optionally, the light shading module 61 covers more than half of the front windshield in the second state.\",\n \"In one embodiment, in the first state, the Visible Light Transmittance (VLT) of the vehicle window is above 10% of ambient light entering through the window, and in the second state, the VLT of the vehicle window is below 50% of ambient light entering through the window.\",\n \"Additionally, the VLT of the vehicle window in the first state is higher than the VLT of the vehicle window in the second state.\",\n \"In another embodiment, in the first state the VLT of the vehicle window is above 70% of ambient light entering through the window, and in the second state, the VLT of the vehicle window is below 30% of ambient light entering through the window.\",\n \"Herein, “ambient light” in the context of a vehicle refers to visible light that is not controlled by the vehicle, such as light arriving from: the sun, lights of other vehicles, street/road lighting, and various reflections from elements such as windows.\",\n \"In some embodiments, utilizing the light shading module 61 may improve the quality of images viewed via the HMD 62 when the light shading module 61 is in the second state.\",\n \"Optionally, the perceived contrast of the optical see-through component is better when the light shading module is in the second state compared to when the light shading module 61 is in the first state.\",\n \"Various types of light shading modules may be utilized in embodiments described herein.\",\n \"In one embodiment, the light shading module 61 is a movable physical element configured to reduce the intensity of the ambient light entering into the vehicle compartment through the vehicle window.\",\n \"Optionally, the light shading module is unfurled on the inside of the compartment in order to block at least 50% of the ambient light intensity.\",\n \"Optionally, the light shading module is unfurled on the outside of the compartment in order to block at least 50% of the ambient light intensity.\",\n \"FIG.\",\n \"13a illustrates a first mode where the occupant sees the outside environment through the optical see-through component.\",\n \"This figure illustrates the view that the occupant sees when looking outside through the window.\",\n \"FIG.\",\n \"13b illustrates a second mode where the occupant sees the outside environment through the VST.\",\n \"In this example, the outside environment is a bit different, and there is also a virtual Superman floating near the tree.\",\n \"In another embodiment, the light shading module 61 may be a curtain.\",\n \"FIG.\",\n \"14 illustrates a VST over a curtain.\",\n \"FIG.\",\n \"15 illustrates a light shading module that is unfurled on the inside of the compartment.\",\n \"FIG.\",\n \"16 illustrates a light shading module that is unfurled on the outside of the compartment.\",\n \"And in yet another embodiment, the vehicle window is made of a material that is able to serve as the light shading module 61 by changing its transparency properties.\",\n \"The camera is fixed to the vehicle, and configured to take video of the outside environment.\",\n \"For example, the camera may be based on at least one of the following sensors: a CCD sensor, a CMOS sensor, a near infrared (NIR) sensor, an infrared sensor (IR), and a device based on active illumination such as a LiDAR.\",\n \"The processor is configured to generate, based on the video, a video see-through (VST 19) that represents the outside environment from a point of view of an occupant looking to the outside environment through at least a portion of the vehicle window.\",\n \"Optionally, the processor is further configured not to generate the VST 19 when the HMD 62 operates in the first mode.\",\n \"The HMD 62 comprises an optical see-through component and a display component.\",\n \"Optionally, the HMD 62 is configured to operate according to a first mode of operation when the occupant looks at the direction of the vehicle window and the light shading module 61 is in the first state, and to operate according to a second mode of operation when the occupant looks at the direction of the vehicle window and the light shading module 61 is in the second state.\",\n \"The total intensity of the VST light, emitted by the display component and reaching the occupant's eyes, is higher in the second mode than in the first mode.\",\n \"In one embodiment, in the first mode, intensity of light that reaches the occupant's eyes via the optical see-through component is higher than intensity of light from the VST that is emitted by the display component and reaches the occupant's eyes.\",\n \"And in the second mode, the intensity of light from the environment that reaches the occupant's eyes via the optical see-through component is lower than the intensity of light from the VST that is emitted by the display component and reaches the occupant's eyes.\",\n \"In one example, the total intensity of VST light, emitted by the display component and reaching the occupant's eyes, is at least 50% higher in the second mode than in the first mode.\",\n \"In some embodiments, the display component may be based on a digital display that produces the virtual image (such as in Oculus rift), direct retina illumination (such as in Magic Leap), or other methods that are capable of producing the virtual image.\",\n \"In one embodiment, the system described above optionally includes an occupant tracking module configured to calculate the point of view of the occupant based on measurements of a sensor.\",\n \"Optionally, the occupant tracking module is the HMD tracking module 27.Optionally, in this embodiment, the processor is further configured to render the VST based on data received from the occupant tracking module.\",\n \"Optionally, the display is a three dimensional (3D) display configured to show the occupant the VST, such that point of gaze of the occupant, while looking via the 3D display device, is most of the time beyond the location of the light shading module 61.In some embodiments, an occupant of a vehicle may have the opportunity to view video see-through (VST), which is video generated based on video of the environment outside the vehicle.\",\n \"VST can often replace the need to look out of a window (if the vehicle has windows).\",\n \"Some examples of scenarios in which VST may be available in a vehicle include a windowless vehicle, a vehicle with shaded windows having VLT below 30%, and/or when the occupant wears a VR headset.\",\n \"While traveling in such a vehicle, the occupant may benefit from gaining a view to the outside environment when an unexpected driving event occurs.\",\n \"By being made aware of the event, the occupant is less likely to be surprised, disturbed, and/or distressed by the event.\",\n \"While traveling in a vehicle, an occupant of the vehicle may not always be aware of the environment outside and/or of what actions the vehicle is about to take (e.g., breaking, turning, or hitting a speedbump).\",\n \"Thus, if such an event occurs without the occupant being aware that it is about to happen, this may cause the occupant to be surprised, disturbed, distressed, and even physically thrown off balance (in a case where the event involves a significant change in the balance of the physical forces on the occupant).\",\n \"This type of event is typically referred to herein as a Sudden Decrease in Ride Smoothness (SDRS) event.\",\n \"Some examples of SDRS events include at least one of the following events: hitting a speed bump, driving over a pothole, climbing on the curb, making a sharp turn, a hard breaking, an unusual acceleration (e.g., 0-100 km/h in less than 6 seconds), and starting to drive after a full stop.\",\n \"In some embodiments, an SDRS event takes place at least 2 minutes after starting to travel and it is not directly related to the act of the starting to travel.\",\n \"Additionally, the SDRS event takes place at least 2 minutes before arriving to the destination and is not directly related to the act of arriving at the destination.\",\n \"In one example, a sentence such as “an SDRS event is imminent” refers to an SDRS event that is: (i) related to traveling in the vehicle, and (ii) expected to happen in less than 30 seconds, less than 20 seconds, less than 10 seconds, or less than 5 seconds.\",\n \"In another example, a sentence such as “an SDRS event is imminent” may refer to an event that starts at that instant, or is about to start within less than one second.\",\n \"The following is a description of an embodiment of a video system that may be used to increase awareness of an occupant of a vehicle regarding an imminent SDRS.\",\n \"In one embodiment, a video system for an autonomous on-road vehicle includes at least autonomous-driving control system 65, a camera (such as camera 12), a processor (such as processor 18), and video module 66.FIG.\",\n \"17 is a schematic illustration of at least some of the relationships between the system elements mentioned above.\",\n \"The autonomous-driving control system 65 is configured to generate, based on trajectory of the vehicle and information about the road, an indication indicative of whether a Sudden Decrease in Ride Smoothness (SDRS) event is imminent.\",\n \"Optionally, the autonomous-driving control system 65 receives at least some of the information about the road from at least one of the following sources: sensors mounted to the vehicle, sensors mounted to nearby vehicles, an autonomous-driving control system 65 used to drive a nearby vehicle, and a database comprising descriptions of obstacles in the road that are expected to cause intense movement of the vehicle.\",\n \"In one example, the database comprising the descriptions of the obstacles includes one or more of the following types of data: locations of speed bumps, locations of potholes, locations of stop signs, and locations of sharp turns in the road.\",\n \"In one embodiment, the autonomous-driving control system 65 is configured to generate the indication indicative of whether an SDRS event is imminent based on at least one of the following configurations: (i) the autonomous-driving control system 65 receives images of the road from a camera, and calculates the indication based on the vehicle trajectory and image analysis of the images, (ii) the autonomous-driving control system 65 receives from a radar reflections of electromagnetic waves from the road, and calculates the indication based on the vehicle trajectory and signal processing of the reflections, and (iii) the autonomous-driving control system 65 receives a notification from a detailed road map, and calculates the indication based on the vehicle trajectory and the notification.\",\n \"The camera, which is mounted to the vehicle, is configured to take video of the environment outside the vehicle.\",\n \"Optionally, the data captured by the camera comprises 3D data.\",\n \"The processor is configured to generate a video see-through (VST) based on the video taken by the camera.\",\n \"The video module 66 is configured to select a first mode of presentation, in which a video-unrelated-to-the-VST (VUR) is presented on the foveal vision region of the occupant, at eye level, responsive to the indication not indicating that an SDRS event is imminent.\",\n \"The video module 66 is further configured to select a second mode of presentation, in which the VST is presented on the foveal vision region of the occupant, at eye level, responsive to the indication indicating that an SDRS event is imminent.\",\n \"Optionally, the VST captures more than 50% of the foveal vision region of the occupant in the second mode of presentation.\",\n \"In some embodiments, presenting video on the foveal vision region comprises presenting images with at least 50% transparency.\",\n \"Herein, “foveal vision” refers to an angle of about 5° of the sharpest field of vision.\",\n \"In one embodiment, in the first mode of presentation, the VUR is presented on the foveal vision region of the occupant with opacity A, and the VST is presented on the foveal vision region of the occupant with opacity B, where A>B>0.Optionally, a normalized opacity parameter takes a value from 0.0 to 1.0, and the lower the value the more transparent the video is.\",\n \"In this embodiment, in the second mode of presentation, the VUR is presented on the foveal vision region of the occupant with opacity A′, and the VST is presented on the foveal vision region of the occupant with opacity B′, where B′>B and B′>A′.\",\n \"In optional embodiments, one or more of the following values may be true: A′>0, B=0, and A′=0.Herein, “partially transparent” refers to opacity below one and above zero.\",\n \"Having the VST presented when an SDRS event is imminent can make the occupant be aware and prepared for the SDRS event.\",\n \"Thus, the occupant is less likely to be startled, distressed, and/or physically thrown off balance by the SDRS event.\",\n \"In one example, the SDRS event involves hitting a speedbump, while the occupant views a movie.\",\n \"About 5 seconds prior to hitting the speedbump, a partially transparent window displaying VST in which the speedbump is highlighted (e.g., flashing red) is presented on the foveal vision region of the occupant for a couple seconds (e.g., by being presented in the center of the movie).\",\n \"This way upon hitting the speedbump, the occupant is not startled by the event.\",\n \"In another example, the autonomous-driving control system 65 determines that a “hard breaking” is required, e.g., in order to avoid collision with a vehicle ahead that slowed unexpectedly.\",\n \"In this example, the occupant may be working on a virtual desktop, and within 100 milliseconds of when the determination is made that the vehicle is about to rapidly deaccelerate (a “hard breaking”), the VST depicting the rear of the vehicle ahead is displayed in the center of the virtual desktop.\",\n \"This way the occupant is immediately made aware of why the vehicle is breaking and this notification may prompt the occupant to seek a more appropriate posture for the breaking.\",\n \"Some illustrations of utilization of the different modes of operation are given in the following figures.\",\n \"FIG.\",\n \"18a illustrates presenting VUR responsive to not receiving from the autonomous-driving control system 65 an indication that an SDRS event is imminent.\",\n \"This figure has two parts, the left part shows the vehicle driving over a clean road, and the right part shows the VUR.\",\n \"FIG.\",\n \"18b illustrates presenting VST responsive to receiving from the autonomous-driving control system 65 an indication that an SDRS event is imminent.\",\n \"The figure has two parts, the left part shows the vehicle about to drive over a pothole, and the right part shows a small window showing the pothole over the VUR (optionally to warn the occupant).\",\n \"FIG.\",\n \"18c illustrates presenting VST responsive to receiving from the autonomous-driving control system 65 an indication that an SDRS event is imminent.\",\n \"The figure has two parts, the left part shows the vehicle about to enter a sharp turn, and on the right part shows a small window showing the sharp turn over the VUR (optionally to warn the occupant).\",\n \"Traditional vehicles typically have a front windshield that offers occupants of the vehicle a frontal view of the outside environment.\",\n \"However, in some embodiments, this frontal view may be provided using the VST.\",\n \"For example, in one embodiment, the vehicle includes a nontransparent element, which is coupled to the vehicle, and obstructs at least 30 degrees out of the frontal horizontal unaided FOV to the outside environment of an occupant at eye level.\",\n \"In one example of a standard vehicle, such as Toyota Camry model 2015, the frontal horizontal unaided FOV extends from the left door through the windshield to the right door.\",\n \"The use of the nontransparent element improves the safety of the occupant during a collision compared to a similar vehicle having the same total weight and comprising a transparent glass window instead of the nontransparent element.\",\n \"The nontransparent element may be coupled to the vehicle in various configurations, in embodiments described herein.\",\n \"In one embodiment, the nontransparent element is fixed to the vehicle at an angle, relative to the occupant, that is covered by the field of view of the VST, and the nontransparent element features visible light transmittance (VLT) below 10% of ambient light.\",\n \"Various types of displays may be utilized to present the occupant with video (e.g., the VST and/or the VUR).\",\n \"In one embodiment, the video is presented to the occupant on a screen coupled to the vehicle compartment.\",\n \"In one example, the screen coupled to the vehicle compartment utilizes parallax barrier technology.\",\n \"A parallax barrier is a device located in front of an image source, such as a liquid crystal display, to allow it to show a stereoscopic image or multiscopic image without the need for the viewer to wear 3D glasses.\",\n \"The parallax barrier includes a layer of material with a series of precision slits, allowing each eye to see a different set of pixels, thus creating a sense of depth through parallax.\",\n \"In another embodiment, the occupant wears a head-mounted display (HMD), and the HMD is used to present the video to the occupant.\",\n \"Optionally, the HMD is a VR headset, and as a result of presenting the VST, the occupant does not need to remove the VR headset in order to see the cause of the SDRS event.\",\n \"In some embodiments, the video module 66 may be selective regarding indications of which SRDS events may prompt it to operate in the second mode of operation.\",\n \"For example, if the occupant is engaged in a game, the video module 66 may refrain from presenting the VST in the foveal vision region if the vehicle is about to make a sharp turn.\",\n \"However, it may optionally still present the VST in the foveal vision region if the SDRS event involves something that may be more forcefully felt by the occupant, such as extreme evasive maneuvering performed to avoid a collision.\",\n \"In some embodiments, the video module 66 may determine whether to show a VST responsive to an SRDS event (in the second mode of operation) based on the level of concentration of the occupant.\",\n \"For example, if the occupant is deeply engaged in a certain activity (e.g., in work or playing a game) above a threshold, the video module 66 may refrain from operating in the second mode for certain SDRS events that would cause the video module 66 to operate in the second mode were the occupant engaged in the certain activity below the threshold.\",\n \"In one example, the engagement level may be based on the occupant's level of concentration, as measured by a wearable sensor (such as an EEG headset or a smartwatch) or a sensor fixed to the compartment (such as an eye tracker, a thermal camera, or a movement sensor embedded in the seat).\",\n \"Presenting an occupant of a vehicle with video see-through (VST) of the outside environment from a point of view of the occupant can help the occupant be prepared for various events that may be considered to cause a Sudden Decrease in Ride Smoothness (SDRS events).\",\n \"Some examples of SDRS events include the following events: hitting a speed bump, driving over a pothole, climbing on the curb, making a sharp turn, a hard breaking, an unusual acceleration (e.g., 0-100 km/h in less than 6 seconds), and starting to drive after a full stop.\",\n \"In order for the occupant to become aware of an imminent SDRS event, the VST needs to be presented in an attention-grabbing way.\",\n \"For example, when an SDRS event is imminent, the VST that describes the environment is brought to the center of the occupant's attention by displaying it at eye level and/or increasing the size of the VST (compared to other times when an SDRS event is not imminent).\",\n \"The following is a description of an embodiment of a video system that may be used to increase awareness of an occupant of a vehicle regarding an imminent SDRS by making the VST more prominent for an imminent SDRS.\",\n \"In one embodiment, a video system for an autonomous on-road vehicle includes at least the autonomous-driving control system 65, a camera, and a processor.\",\n \"In this embodiment, the occupant is engaged, at least part of the time, in entertainment- or work-related activities, which involve presentation of video-unrelated-to-the-VST (VUR) to the occupant, for example, on a screen coupled to the compartment of the vehicle or a HMD worn by the occupant.\",\n \"Some examples of such content (common in the year 2016) include cinema movies, broadcast TV shows, standard web browsers, and Microsoft Office 2016 applications (such as Word, Excel and PowerPoint).\",\n \"The camera, which is mounted to the vehicle, is configured to take video of the environment outside the vehicle.\",\n \"The processor is configured to generate, based on the video taken by the camera, a video see-through (VST) of outside environment from a point of view of an occupant of the vehicle.\",\n \"Optionally, the occupant is in a front seat of the vehicle (such that no other occupant in the vehicle is positioned ahead of the occupant).\",\n \"In some embodiments, the processor is configured to present video, which may include VUR and/or VST, to the occupant using different presentation modes, depending on whether an SDRS event is imminent.\",\n \"For example, the video may be presented according to first or second modes, depending on whether an SDRS event is imminent.\",\n \"Optionally, the VST captures in the video according to the first mode a diagonal FOV of at least 3°, 5°, or 10° of the occupant's FOV.\",\n \"Optionally, the VST is not presented in the foveal vision region of the occupant in the video according to the first mode, while the VST is presented in the foveal vision region of the occupant in the video according to the second mode.\",\n \"In one embodiment, responsive to an indication that is not indicative of an imminent SDRS event (generated by the autonomous-driving control system 65), the processor is configured to provide the occupant video according to the first mode.\",\n \"In the video according to the first mode, the occupant is presented with video that comprises a video-unrelated-to-the-VST (VUR) at eye level in the direction of forward traveling.\",\n \"Additionally, the video may comprise a video see-through (VST) of outside environment that is not presented at eye level in the direction of forward traveling.\",\n \"Receiving an indication indicative that an SDRS event is imminent may change the way video is presented to the occupant.\",\n \"Optionally, this change is made without receiving a command to do so from the occupant.\",\n \"In one embodiment, responsive to the indication indicating that an SDRS event is imminent, the processor is configured to provide video to the occupant video according to the second mode.\",\n \"In the video according to the second mode, the occupant is presented with video that comprises the VST, presented at eye level in the direction of forward traveling.\",\n \"Optionally, if the video according to the first mode includes VST, then the size of the VST window in the video according to the second mode is larger by at least 25% relative to the size of the VST window in the video according to the first mode.\",\n \"Optionally, the video according to the second mode includes presenting the VUR in the background (e.g., the VST is overlaid above the VUR).\",\n \"Optionally, while providing the video according to the second mode, responsive to an updated indication that does not indicate that an SDRS event is imminent, the processor is further configured to switch back to provide the video according to the first mode to the occupant.\",\n \"The following figures illustrate various ways in which the videos according to the first and second modes may be utilized.\",\n \"FIG.\",\n \"19a illustrates presenting a VUR, which is a movie showing a person skiing, responsive to not receiving from the autonomous-driving control system 65 an indication that an SDRS event is imminent.\",\n \"This figure has two parts, the left part shows the vehicle driving over a clean road, and the right part shows the VUR with a small VST on the right.\",\n \"FIG.\",\n \"19b illustrates presenting a VST responsive to receiving from the autonomous-driving control system 65 an indication that an SDRS event is imminent.\",\n \"This figure has two parts, the left part shows the vehicle about to drive over a speed bump, and the right part shows the VUR but now with a big VST on the right.\",\n \"In this example, the big VST captures about half of the VUR and shows the speed bump.\",\n \"FIG.\",\n \"19c illustrates presenting a partially transparent VST responsive to receiving from the autonomous-driving control system 65 an indication that an SDRS event is imminent.\",\n \"Here, the big VST (that captures about half of the VUR and shows the speed bump) is presented as partially transparent layer over the VUR in order to show the occupant both the VUR and the VST.\",\n \"In one embodiment, presenting to the occupant video according to the second mode involves presenting the VUR behind the VST, and the size and location of the VUR in the video according to the second mode is essentially the same as the size and location of the VUR in the video according to the first mode.\",\n \"Optionally, this means that there is a difference of less than 10% in the size and location of the VURs in the videos according to the first and second modes.\",\n \"In another embodiment, the VUR is presented in a diagonal FOV of at least 10 degrees, and is not based on the video taken by the camera.\",\n \"In some embodiments, the VUR may be unrelated to the purpose of the traveling in the vehicle.\",\n \"For example, the VUR may include videos related to the following activities: watching cinema movies, watching TV shows, checking personal emails, playing entertainment games, and surfing in social networks.\",\n \"In some embodiments, the occupant's field of view (FOV) to the outside environment is obstructed by a nontransparent element, and the VST represents at least a portion of the obstructed FOV.\",\n \"Optionally, the occupant uses a VR headset and the obstruction is due to a nontransparent element belonging to the VR headset.\",\n \"Additionally or alternatively, the obstruction may be due to the vehicle's compartment; in this case the nontransparent element may be an SAEDP, a safety beam, and/or a crumple zone at eye level, which obstruct at least 30 degrees out of the frontal horizontal unaided FOV to the outside environment of the occupant at eye level.\",\n \"When traveling in a vehicle, an occupant of the vehicle may not always be viewing the outside environment.\",\n \"For example, the occupant may be engaged in work- or entertainment-related activities.\",\n \"Additionally, in some vehicles, the occupant may not have a good view of the outside environment most of the time, or even all of the time.\",\n \"For example, the vehicle may have very few (or no) windows, or the vehicle may have a shading mechanism that reduces the light from the outside.\",\n \"However, there are times when the occupant should be made aware of the outside environment, even though the occupant may not be actively driving the vehicle.\",\n \"For example, the occupant may be made aware of the outside environment in order to make the occupant prepared for an event that causes a Sudden Decrease in Ride Smoothness (an SDRS event).\",\n \"Some examples of SDRS events include the following events: hitting a speed bump, driving over a pothole, climbing on the curb, making a sharp turn, a hard breaking, an unusual acceleration (e.g., 0-100 km/h in less than 6 seconds), and starting to drive after a full stop.\",\n \"In order for the occupant to become aware of an imminent SDRS event, in some embodiments that involve a vehicle that has a shading module that controls how much ambient light is let in, when an SDRS event is imminent the vehicle may increase the amount of light that enters via a window.\",\n \"This additional light can give an occupant a better view of the outside environment, which can make the occupant aware and better prepared for the SDRS.\",\n \"The following is a description of an embodiment of a system that may be used to increase awareness of an occupant of a vehicle regarding an imminent SDRS by enabling more ambient light to enter a vehicle via a window.\",\n \"In one embodiment, a shading system for a window of an autonomous on-road vehicle includes at least the autonomous-driving control system 65, a shading module, and a processor.\",\n \"FIG.\",\n \"20a illustrates a smart glass shading module that operates according to an indication that an SDRS event is not imminent.\",\n \"This figure has two parts, the left part shows the vehicle driving over a clean road, and the right part shows that the smart glass window blocks most of the ambient light (illustrated in the figure by the tree outside that is invisible to the occupant).\",\n \"FIG.\",\n \"20b illustrates the smart glass shading module that operates according to an indication that an SDRS event is imminent.\",\n \"This figure has two parts, the left part shows the vehicle about to drive over a pothole, and the right part shows that the smart glass window does not block the ambient light (illustrated in the figure by the tree outside that is visible to the occupant).\",\n \"The shading module is configured to control the amount of ambient light that enters the vehicle via the window.\",\n \"Optionally, the window is a front-facing window (e.g., a windshield).\",\n \"Optionally, the window is a side-facing window.\",\n \"There are various types of shading modules that may be utilized in different embodiments.\",\n \"In one embodiment, the shading module comprises a curtain.\",\n \"Optionally, the curtain covers most of the area of the window.\",\n \"Optionally, the curtain may open and close with the aid of an electromechanical device, such as a motor, based on commands issued by the processor.\",\n \"In another embodiment, the shading module is a movable physical element configured to reduce the intensity of the ambient light entering through the vehicle window into the vehicle compartment.\",\n \"For example, the shading module may include various forms of blinds, a shutter, or a sliding element.\",\n \"Optionally, the shading module may be unfurled on the inside of the vehicle compartment in order to block more than 70% of the ambient light intensity.\",\n \"Optionally, the shading module may be unfurled on the outside of the vehicle compartment in order to block more than 70% of the ambient light intensity.\",\n \"In yet another embodiment, the shading module comprises a smart glass able to change its light transmission level.\",\n \"Optionally, the smart glass is a vehicle window smart glass that comprises suspended particle devices (SPDs) film.\",\n \"Smart glass window may also be known as a switchable glass, a smart window, and/or a switchable window.\",\n \"Smart glass is glass or glazing whose light transmission properties are altered when voltage, current, light or heat is applied.\",\n \"Examples of electrically switchable smart glass include: suspended particle devices (SPDs), electrochromic devices, transition-metal hydride electrochromics devices, modified porous nano-crystalline films, polymer dispersed liquid crystal devices, micro-blinds, and thin coating of nanocrystals embedded in glass.\",\n \"Examples of non-electrical smart glass include: mechanical smart windows, Vistamatic®, and Sunvalve.\",\n \"The processor is configured to command the shading module to operate in different modes based on indications generated by the autonomous-driving control system 65.In some embodiments, the processor is configured to command the shading module to operate in different modes that allow different amounts of the ambient light to enter the vehicle via the window, depending on whether an SDRS event is imminent.\",\n \"For example, shading module may operate in first or second modes, depending on whether an SDRS event is imminent.\",\n \"Optionally, in the first mode the shading module blocks more of the ambient light entering through the vehicle window than in the second mode.\",\n \"Optionally, the increased ambient light in the second mode can help make the occupant more aware of the outside environment, which can enable the occupant to prepare for the SDRS event.\",\n \"In one embodiment, responsive to an indication that no SDRS event is imminent, the processor is configured to command a shading module to operate in a first mode in which the shading module blocks more than 30% of ambient light entering through a window of the vehicle.\",\n \"Receiving an indication indicative that an SDRS event is imminent may change the amount of ambient light that enters the vehicle via the window.\",\n \"Optionally, this change is made without receiving a command to do so from the occupant.\",\n \"In one embodiment, responsive to an indication that an SDRS event is imminent, the processor is configured to command the shading module to operate in the second mode in which the shading module blocks less than 90% of the ambient light entering through the vehicle window.\",\n \"Some aspects of this disclosure include a system that can show an occupant of a vehicle and Object Of Interest (OOI) in the outside environment, which the occupant would otherwise miss (e.g., due to being engaged in work- or entertainment-related activities and/or having no direct view of the outside environment).\",\n \"In one embodiment, a system configured to identify an Object Of Interest (OOI) in the outside environment, and to present to an occupant of an autonomous on-road vehicle a video see-through (VST) that comprises the OOI, includes at least a camera (such as camera 12), a processor (such as processor 18), and a video module (such as video module 66).\",\n \"Different types of things may be considered an OOI in different embodiments.\",\n \"In one embodiment, the OOI is selected from a set comprising: types of vehicles, types of scenery, and types of people.\",\n \"Optionally, the system may include a user interface configured to present a menu that enables the occupant to select the types of OOI, which when identified, will be presented in the second mode of presentation.\",\n \"In one example, an OOI may be any type of high-end vehicle (e.g., a Porsche).\",\n \"In another example, an OOI may include an ocean view.\",\n \"The camera, which is mounted to the vehicle, is configured to take video of the environment outside the vehicle.\",\n \"Optionally, the data captured by the camera comprises 3D data.\",\n \"The processor is configured to generate, based on the video taken by the camera, a video see-through (VST) of outside environment from a point of view of an occupant of the vehicle.\",\n \"Optionally, the occupant is in a front seat of the vehicle (such that no other occupant in the vehicle is positioned ahead of the occupant).\",\n \"The video module is configured to present, to the occupant, video that captures diagonal field of view (FOV) of at least 10 degrees, at eye level.\",\n \"Optionally, the video module is further configured to select a mode of operation based on whether an indication is received that is indicative of whether video taken by the camera include the OOI.\",\n \"Optionally, changing a mode of operation is done without an expressed command at that time by the occupant.\",\n \"In one embodiment, when not receiving an indication that the images includes the OOI, the video module is configured to select a first mode of presentation, in which a video-unrelated-to-the-VST (VUR) is presented on the foveal vision region of the occupant.\",\n \"And responsive to receiving the indication that the images include the OOI, the video module is further configured to select a second mode of presentation, in which the VST is presented on the foveal vision region of the occupant.\",\n \"There are various ways in which an indication of the OOI may be generated in different embodiments.\",\n \"In one embodiment, the system includes an image processing module configured to identify the OOI in the VST and to generate the indication.\",\n \"Various image processing techniques and/or image identification methods known in the art may be utilized by the image processing module for this task.\",\n \"In another embodiment, the system may include the autonomous-driving control system 65 configured to utilize a positioning system, such as GPS coordinates, to identify that the vehicle reached the OOI and to generate the indication.\",\n \"Optionally, the occupant may define which places may be OOIs and/or what types of locations are to be considered OOIs (e.g., historical monuments, nice scenery, etc.).\",\n \"In still another embodiment, the system may include a crowd-based module configured to identify the OOI based on feedback received from many different occupants who watched VSTs comprising the OOI.\",\n \"Optionally, this feedback may be derived based on indications of how other occupants felt about the VST (when it depicted certain content corresponding to OOIs).\",\n \"For example, points of interest may be determined according to affective crowd data, determine based on how other occupants felt about what they saw, and optionally find places where the crowd affective response was positive (e.g., blooming of flowers, etc.).\",\n \"Optionally, some occupants who watched the video related to the unhindered FOV for long periods (or have a physical window) may be monitored to see when an interesting view is encountered.\",\n \"Points of interest may involve items identified in the exterior environment using image analysis, including presenting the VST when one or more of the following happens: passing a fancy vehicle, passing someone the occupant knows, passing a vehicle accident, passing a police officer, having a sunset view, and passing an animal the occupant is interested in.\",\n \"In one embodiment, the system may receive an indication that the occupant is feeling at least one of nauseous and claustrophobic, and consequently present the VST in order to help the occupant to confront the feeling.\",\n \"For example, when there is a serious spike (e.g., increase in heart-rate and sweating), then the system may present the VST automatically.\",\n \"The system may also present a “normal” interior to the occupant (e.g., natural lighting settings).\",\n \"Optionally, when digital content is consumed (e.g., a game or a movie), the system may check whether the affective spike (e.g., increased excitement) is due to the content or due to the experience of being in the vehicle with AR or VR.\",\n \"If it is the former case, then the system might not present the VST.\",\n \"Some aspects of this disclosure involve an autonomous on-road vehicle that includes a nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) that is coupled to the compartment of the vehicle and is located, during normal driving, at eye level in front of an occupant who sits in a front seat of the vehicle.\",\n \"Additionally, the vehicle includes a stiff element that is configured to support the SAEDP and to resist deformation during collision in order to reduce compartment intrusion.\",\n \"The stiff element is located, during normal driving, at eye level between the SAEDP and the outside environment.\",\n \"Thus, the combination of the SAEDP and the stiff element offers the occupant an increased level of protection, e.g., in the case of a collision, compared to a vehicle in which a traditional window is in place at eye level in the front of the vehicle.\",\n \"However, due to it being nontransparent, placing the SAEDP at eye level may obstruct the occupant's view to the outside.\",\n \"Thus, in order to offer the occupant such a view, in some embodiments, the vehicle also includes a camera configured to take video of the outside environment in front of the occupant, and a computer configured to generate, based on the video, a representation of the outside environment in front of the occupant at eye level.\",\n \"This representation may be provided to the occupant using various types of displays.\",\n \"One non-limiting advantage of the vehicle described above is that it increases the safety of the occupant in the case of a collision, without prohibiting the occupant from obtaining a view of the outside environment.\",\n \"In one embodiment, an autonomous on-road vehicle includes a compartment, which one or more occupants may occupy while traveling in the vehicle (e.g., by sitting in seats).\",\n \"Coupled to the front of the compartment is a Shock-Absorbing Energy Dissipation Padding (SAEDP) and a stiff element that supports the SAEDP.\",\n \"Optionally, the SAEDP is nontransparent.\",\n \"The stiff element is located, during normal driving, at eye level between the SAEDP and the outside environment.\",\n \"Additionally, the vehicle includes a camera (e.g., camera 142 or structure 147 that comprises multiple cameras), which is configured to take video of the outside environment in front of the occupant, and a computer (e.g., computer 143) that is configured to generate, based on the video, a representation of the outside environment in front of the occupant at eye level.\",\n \"Optionally, the camera, and/or each of the cameras in the structure 147, may be based on at least one of the following sensors: a CCD sensor, a CMOS sensor, a near infrared (NIR) sensor, an infrared sensor (IR), and a device based on active illumination such as a LiDAR.\",\n \"Optionally, when the camera comprises multiple cameras, the multiple cameras are directed to multiple directions around the vehicle, and the multiple cameras support generating multiple representations of the outside environment from different points of view.\",\n \"It is to be noted that in some embodiments, the SAEDP may be fixed at its location both in normal driving and in times that are not considered to correspond to normal driving, while in other embodiments, the SAEDP may change its location during at least some of the times that do not correspond to normal driving.\",\n \"The SAEDP is coupled to the compartment in such a way that it is located, during normal driving, at eye level in front of an occupant who sits in a front seat of the vehicle.\",\n \"Different types of SAEDPs may be utilized in different embodiments.\",\n \"In one embodiment, the SAEDP comprises a passive material that is less stiff than a standard automotive glass window.\",\n \"The passive material is configured to protect the occupant's head against hitting the inner side of the vehicle compartment during a collision.\",\n \"Optionally, the passive material has thickness greater than at least one of the following thicknesses: 1 cm, 2 cm, 5 cm, 10 cm, 15 cm, and 20 cm.\",\n \"Optionally, the thickness of the passive material may refer to the average thickness of the SAEDP across the portion of the SAEDP at eye level.\",\n \"Alternatively, the thickness may refer to the maximal thickness at some position of the SAEDP (which is at least one of the values mentioned above).\",\n \"In another embodiment, the SAEDP comprises a pneumatic pad that is configured to inflate in order to protect the occupant's head against hitting the inner side of the vehicle compartment during collision.\",\n \"In some examples, the pneumatic pads may be formed from an elastomeric material providing chambers containing air or another gas.\",\n \"Optionally, the chambers are retained in compressed deflated condition until being inflated by the admission of gas pressure controlled by the vehicle's autonomous-driving control system that is responsible to estimate the probability and severity of an imminent collision.\",\n \"Additionally or alternatively, the chambers may be provided with restricted passages limiting the flow out from the chambers to provide shock-absorbing energy dissipation to reduce the rebound effect.\",\n \"U.S. Pat.\",\n \"No.\",\n \"5,382,051 discloses examples for pneumatic pads that can be used with some of the embodiments.\",\n \"In yet another embodiment, the SAEDP comprises an automotive airbag, which is configured to protect the occupant's head against hitting the inner side of the vehicle compartment during collision.\",\n \"In one example, during normal driving, the airbag is in a stowed state.\",\n \"The airbag is coupled to an inflator configured to inflate the airbag with gas to an inflated state, upon receiving an indication indicative of a probability of an impact of the vehicle exceeding a threshold.\",\n \"In this example, the airbag is located, when in the stowed state, at eye level in front of the occupant.\",\n \"In some embodiments, the compartment may include a door, and the SAEDP is physically coupled to the door from the inside, such that the SAEDP moves with the door as the door opens and/or closes.\",\n \"In some embodiments, the vehicle may include a second SAEDP coupled to the outer front of the vehicle to minimize damage to a pedestrian during a pedestrian-vehicle collision.\",\n \"In one embodiment, the stiff element that supports the SAEDP is nontransparent.\",\n \"In another embodiment, the stiff element may be automotive laminated glass or automotive tempered glass.\",\n \"Optionally, the structure of the vehicle comprises a crumple zone located at eye level between the stiff element and the outside environment.\",\n \"The representation of the outside environment is intended to provide the occupant with some details describing the outside environment.\",\n \"In some embodiments, the representation of the outside environment is generated from the point of view of the occupant, and it represents how a view of the outside environment would look like to the occupant, had there been a transparent window at eye level instead of the SAEDP and/or the stiff element.\",\n \"Optionally, a display is utilized to present the representation to the occupant.\",\n \"Various types of displays may be utilized in different embodiments to present the representation of the outside environment to the occupant.\",\n \"In one embodiment, the display is comprised in an HMD, and the vehicle further comprises a communication system configured to transmit the representation to the HMD.\",\n \"For example, the HMD may be a virtual reality system, an augmented reality system, or a mixed-reality system.\",\n \"In one embodiment, the display is supported by at least one of the SAEDP and the stiff element.\",\n \"For example, the display is physically coupled to the SAEDP and/or the stiff element.\",\n \"Optionally, the display is a flexible display.\",\n \"For example, the flexible display may be based on at least one of the following technologies and their variants: OLED, organic thin film transistors (OTFT), electronic paper (e-paper), rollable display, and flexible AMOLED.\",\n \"In one example, the display is flexible enough such that it does not degrade the performance of the SAEDP by more than 20% during a collision.\",\n \"In one example, the performance of the SAEDP is measured by hitting a crash test dummy head against the SAEDP and measuring the head's deceleration using sensors embedded in the head.\",\n \"FIG.\",\n \"21a, FIG.\",\n \"21b, and FIG.\",\n \"22 illustrate various embodiments of the vehicle described above.\",\n \"Each of the illustrated vehicles comprises a cross-section view of the vehicles, where each includes a compartment 145 for a single occupant (in FIG.\",\n \"21b) or more (in FIG.\",\n \"21a and FIG.\",\n \"22).\",\n \"In the figures, much of the compartment is covered with the SAEDP 140, which is nontransparent and comprises a soft passive material (cushiony in its nature).\",\n \"Supporting the SAEDP 140 is a stiff element 141, which in the illustrations comprises portions of the exterior (hull) of the vehicle which may optionally be made of one or more of the following materials: fiber-reinforced polymer, carbon fiber reinforced polymer, steel, and aluminum.\",\n \"The vehicles also include a camera (such as camera 142 and/or structure 147 that houses multiple cameras), which is positioned to capture a front view of the outside environment of the vehicle.\",\n \"Additionally, the vehicles include a computer 143, which may be positioned in various locations in the vehicle.\",\n \"In some embodiments, the computer may be comprised of multiple processors and/or graphics processors that may be located at various locations in the vehicle.\",\n \"The figures illustrate various types of displays that may be utilized to present the occupant with the representation of the outside environment generated by the computer 143 based on the video taken by the camera 142.In FIG.\",\n \"21a the representation is presented via an HMD 144, which may be, for example, a virtual reality HMD.\",\n \"In FIG.\",\n \"21b the representation is presented via an HMD 146, which may be, for example, a mixed-reality headset.\",\n \"And in FIG.\",\n \"22 the representation may be provided via one or more of the displays 150, which are coupled to the compartment.\",\n \"It is to be noted that in the figures described above not all of the described elements appear in each figure.\",\n \"The figures also illustrate various structural alternatives that may be implemented in different embodiments described herein.\",\n \"For example, FIG.\",\n \"21a illustrates a vehicle that includes window 148, which may optionally be an automotive tempered glass window, located in a location in which the head of a belted occupant is not expected to hit during collision.\",\n \"FIG.\",\n \"21b illustrates a vehicle that includes crumple zone 149, which is located at the front of the vehicle at eye level.\",\n \"The figure also illustrates the structure 147 that houses multiple cameras directed to multiple directions around the vehicle.\",\n \"In some embodiments, the representation of the outside environment may be manipulated in order to improve how the outside environment looks to the occupant.\",\n \"Optionally, this may be done utilizing the computer.\",\n \"In one example, manipulating the representation includes at least one of the following manipulations: converting captured video of an overcast day to video of a sunny day by preserving main items in the captured video (such as vehicles and buildings) and applying effects of a sunny day, converting unpleasant environment to a nice one, converting standard vehicles to futuristic or old fashion vehicles, and adding fans standing outside and waiving to the occupant.\",\n \"In one embodiment, the manipulation maintains the main items in the environment, such that the occupant would still know from the manipulated representation where he/she is traveling.\",\n \"In another embodiment, the manipulated representation maintains the main objects in the video of the outside environment, such that the main objects presented in the manipulated video essentially match the main objects that would have been seen without the manipulation.\",\n \"In some embodiments, the vehicle compartment may include an automotive laminated glass window or automotive tempered glass window located in a location where the head of a belted occupant is not expected to hit as a result of collision while traveling in velocity of less than 50 km/h, as illustrated by the dotted rectangle 148 in FIG.\",\n \"21a.\",\n \"In one embodiment, the structure of the vehicle is such that a crumple zone is located at eye level between the stiff element and the outside environment.\",\n \"Various types of vehicles may benefit from utilization of the nontransparent SAEDP supported by the stiff element and in conjunction with the camera and computer, as described above.\",\n \"The following are some examples of different characterizations of vehicles in different embodiments.\",\n \"In one embodiment, the vehicle weighs less than 1,500 kg without batteries, and it is designed to carry up to five occupants.\",\n \"In another embodiment, the vehicle weighs less than 1,000 kg without batteries, and it comprises an engine that is able to sustain continuously at most 80 horsepower.\",\n \"In yet another embodiment, the vehicle weighs less than 1,000 kg and it is designed to carry up to two occupants.\",\n \"In still another embodiment, the vehicle weighs less than 800 kg without batteries, and it comprises an engine that is able to sustain continuously at most 60 horsepower.\",\n \"In yet another embodiment, the vehicle weighs less than 500 kg without batteries and it comprises an engine that is able to sustain continuously at most 40 horsepower.\",\n \"And in still another embodiment, the vehicle weighs less than 400 kg without batteries and is designed to carry up to two occupants.\",\n \"Some aspects of this disclosure involve an autonomous on-road vehicle that includes a nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) that is coupled to the compartment and is located, during normal driving, at eye level to the left of the occupant who sits in a front seat of the vehicle (in the left front seat when the vehicle has more than one front seat).\",\n \"The SAEDP obstructs at least 30 degrees out of the horizontal unaided field of view (FOV) to the outside environment to the left of the occupant at eye level.\",\n \"Additionally, the vehicle includes a stiff element that is configured to support the SAEDP and to resist deformation during collision in order to reduce compartment intrusion.\",\n \"The stiff element is located, during normal driving, at eye level between the SAEDP and the outside environment.\",\n \"Thus, the combination of the SAEDP and the stiff element offers the occupant an increased level of protection, e.g., in the case of a collision to the left side of the vehicle, compared to a vehicle in which a traditional window is in place at eye level on the left side of the vehicle.\",\n \"However, due to it being nontransparent, placing the SAEDP at eye level may obstruct the occupant's view to the outside.\",\n \"Thus, in order to offer the occupant such a view, in some embodiments, the vehicle also includes a camera configured to take video of the outside environment to the left of the occupant, and a computer, which is configured to generate, based on the video, a representation of the outside environment to the left of the occupant at eye level.\",\n \"This representation may be provided to the occupant using various types of displays.\",\n \"One non-limiting advantage of the vehicle described above is that it increases the safety of the occupant in the case of a side collision, without prohibiting the occupant from obtaining a side view of the outside environment.\",\n \"In one embodiment, an autonomous on-road vehicle includes a compartment, which one or more occupants may occupy while traveling in the vehicle (e.g., by sitting in seats).\",\n \"Coupled to the compartment is a Shock-Absorbing Energy Dissipation Padding (SAEDP) and a stiff element that supports the SAEDP.\",\n \"Optionally, the SAEDP is nontransparent.\",\n \"The SAEDP is located, during normal driving, at eye level to the left of the occupant who sits in a front seat of the vehicle.\",\n \"The stiff element is located, during normal driving, at eye level between the SAEDP and the outside environment.\",\n \"Optionally, the stiff element is nontransparent.\",\n \"Optionally, the stiff element may be automotive laminated glass or automotive tempered glass.\",\n \"The vehicle also includes a camera (such as camera 161) that is configured to take video of the outside environment to the left of the occupant, and a computer that is configured to generate, based on the video, a representation of the outside environment to the left of the occupant at eye level.\",\n \"Optionally, the camera comprises multiple cameras directed to multiple directions around the vehicle, and the multiple cameras support generating multiple representations of the outside environment from different points of view.\",\n \"FIG.\",\n \"23 illustrates one embodiment of the autonomous on-road vehicle described above, which shows how an SAEDP protects the occupant during a collision.\",\n \"In the figure, SAEDP 160 (which may comprise a passive material) is coupled to the stiff element 141.When another vehicle collides with the side of the vehicle, the occupants head strikes the soft SAEDP 160, instead of a glass window (which would be positioned there in many conventional vehicles).\",\n \"The SAEDP is coupled to the compartment in such a way that it is located, during normal driving, at eye level to the left of the occupant who sits in a front seat of the vehicle.\",\n \"Optionally, due to its location, the SAEDP obstructs at least 30 degrees out of the horizontal unaided field of view (FOV) to the outside environment to the left of the occupant at eye level.\",\n \"Optionally, the SAEDP obstructs at least 45 degrees or at least 60 degrees out of the horizontal unaided FOV to the outside environment to the left of the occupant at eye level.\",\n \"In one example of a standard vehicle, such as Toyota Camry model 2015, the frontal horizontal unaided FOV extends from the left door through the windshield to the right door.\",\n \"In some embodiments, the SAEDP is fixed to the left door of the vehicle.\",\n \"In one embodiment, the vehicle has a single seat (occupied by the occupant).\",\n \"In another embodiment, the vehicle has two or more front seats and the occupant occupies the leftmost of the two or more front seats.\",\n \"Different types of SAEDPs may be utilized in different embodiments.\",\n \"In one embodiment, the SAEDP comprises a passive material, which is less stiff than a standard automotive glass window, having a thickness greater than at least one of the following thicknesses: 1 cm, 2 cm, 5 cm, 10 cm, 15 cm, and 20 cm.\",\n \"In other embodiments, the SAEDP may include an automotive airbag or a pneumatic pad that is configured to inflate in order to protect the occupant's head against hitting the inner side of the vehicle compartment during collision.\",\n \"In a similar fashion to how the SAEDP and stiff element are utilized to help protect the left side of the occupant, the same setup may be applied to the right side of the vehicle, in order to help protect that side.\",\n \"Thus, in some embodiments, the vehicle may further include a second SAEDP located at eye level to the right of the occupant who sits in the front seat, and a second stiff element located at eye level between the second SAEDP and the outside environment.\",\n \"Optionally, the second SAEDP obstructs at least 20 degrees out of the horizontal unaided FOV to the outside environment to the right of the occupant at eye level, and the computer is further configured to generate a second representation of the outside environment to the right of the occupant.\",\n \"Some aspects of this disclosure involve an autonomous on-road vehicle that includes a nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) that can cover a side window that enables an occupant of the vehicle to see the outside environment.\",\n \"The side window is located at eye level of an occupant who sits in the vehicle.\",\n \"A motor is configured to move the SAEDP over a sliding mechanism between first and second states multiple times without having to be repaired.\",\n \"A processor is configured to receive, from an autonomous-driving control system, an indication that a probability of an imminent collision reaches a threshold, and to command the motor to move the SAEDP from the first state to the second state.\",\n \"In the first state the SAEDP does not block the occupant's eye level view to the outside environment, and in the second state the SAEDP blocks the occupant's eye level view to the outside environment in order to protect the occupant's head against hitting the side window during collision.\",\n \"One non-limiting advantage of the vehicle described above is that it increases the safety of the occupant in the case of a side collision.\",\n \"In one embodiment, an autonomous on-road vehicle includes a side window 170, a nontransparent SAEDP (e.g., SAEDP 171), a motor 172, and a processor 175.The processor 175 is configured to receive, from an autonomous-driving control system (such as autonomous-driving control system 65), an indication indicating that a probability of an imminent collision reaches a threshold, and to command the motor 172 to move the SAEDP 171 from the first state to the second state.\",\n \"In the first state the SAEDP 171 does not block the occupant's eye level view to the outside environment, and in the second state, the SAEDP 171 blocks the occupant's eye level view to the outside environment in order to protect the occupant's head against hitting the side window during collision.\",\n \"Optionally, the processor is configured to command the motor 172 to start moving the SAEDP 171 to the second state at least 0.2 second, 0.5 second, 1 second, or 2 seconds before the expected time of the collision.\",\n \"The motor 172 is configured to move the SAEDP 171 over a sliding mechanism 173 between first and second states multiple times without having to be repaired.\",\n \"For example, during the same voyage, the SAEDP 171 may go up and down multiple times without a need for the occupant or anyone else to repair the SAEDP 171 and/or other components (such as motor 172 or the window 170) in order to the SAEDP 171 to be able to continue its operation correctly (i.e., continue moving up and down when needed).\",\n \"In some examples, the motor 172 is a motor designed to move the SAEDP 171 more than twice, more than 100 times, and/or more than 10,000 times without being replaced.\",\n \"The side window 170 is located at eye level of an occupant who sits in the vehicle, which enables the occupant to see the outside environment.\",\n \"In one embodiment, the side window 170 is a power window.\",\n \"In this embodiment, the power window comprises a window regulator that transfers power from a window motor 177 to the side window glass in order to move it up or down.\",\n \"The motor 172 is coupled to an SAEDP regulator that transfers power from the motor 172 to the SAEDP 171 in order to move it up or down.\",\n \"In this embodiment, the SAEDP regulator is located closer to the inner side of the compartment then the window regulator.\",\n \"Optionally, the motor 172 and the window motor 177 may be of the same type or of different types.\",\n \"In one embodiment, the SAEDP 171 comprises a passive material, which is less stiff than a standard automotive glass window, having thickness greater than at least one of the following thicknesses: 1 cm, 2 cm, 5 cm, 10 cm, 15 cm, and 20 cm.\",\n \"Optionally, the vehicle may include a storage space in a door of the vehicle, which is configured to store the SAEDP 171 in the first state.\",\n \"Additionally or alternatively, the vehicle may include a storage space in the roof of the vehicle, which is configured to store the SAEDP 171 in the first state.\",\n \"Optionally, the SAEDP 171 may move upwards when switching between the first and second states, and the top of the SAEDP has a profile (such as a triangle or a quarter sphere) which reduces the risk of catching the a part of the occupant (e.g., a finger or limb) or the occupant's clothing, between the top of the SAEDP 171 and an upper frame when moving the SAEDP 171 to the second state.\",\n \"In one embodiment, when switching the SAEDP 171 quickly between the first and second states, the SAEDP 171 is configured not to cover a range of 1 to 5 cm of the top height of the window.\",\n \"Optionally, keeping said range unoccupied reduces the risk of catching the occupant's fingers or limb by the edge of the SAEDP 171 when moving the SAEDP 171 to the second state.\",\n \"In some embodiments, the vehicle may include additional SAEDPs that cover additional regions of the vehicle's compartment (besides the side window 170).\",\n \"In one example, the vehicle includes an SAEDP 176 that covers at least a portion of the roof of the vehicle.\",\n \"In some embodiments, the vehicle includes a camera (e.g., camera 178a), which is configured to take video of the outside environment while the SAEDP 171 is in the second state.\",\n \"Additionally, in these embodiments, the vehicle may include a computer (such as computer 13), which is configured to generate a representation of the outside environment based on the video, and a display configured to present the representation of the outside environment to the occupant.\",\n \"The display may be physically coupled to the compartment and/or belong to an HMD.\",\n \"Optionally, the camera is fixed to the SAEDP 171, and thus moves along with the SAEDP 171 when it is moved between the first and second states.\",\n \"Optionally, the display is fixed to the SAEDP 171, and thus moves along with the SAEDP 171 when it is moved between the first and second states.\",\n \"Optionally, the display is configured to show, at eye level, a representation of the outside environment when the SAEDP is in the second state.\",\n \"In one example, the display is a flexible display.\",\n \"In another example, the camera comprises multiple cameras directed to multiple directions around the vehicle, and the computer is configured to generate at least two different representations of the outside environment, from at least two different points of view, for two occupants who sit in the vehicle.\",\n \"In some embodiments, in addition to raising the SAEDP 171, one or more of the displays mentioned above is utilized to present the occupant a video of the threat and the predicted trajectory that could result in the collision, in order to explain why the SAEDP 171 is being moved to the second state.\",\n \"FIG.\",\n \"24a and FIG.\",\n \"24b illustrate an example of a vehicle in which the side window may be covered by an SAEDP that can move up and down.\",\n \"The figures illustrate cross-sections of the vehicle, which show how the SAEDP 171 may move from the first state (in FIG.\",\n \"24a) to the second state (in FIG.\",\n \"24b).\",\n \"The dotted line 179 indicates that the SAEDP 171 does not close the entire gap over the window (e.g., in order to avoid catching the occupant's hair).\",\n \"The figures also illustrate sliding mechanism 173, which may be utilized to guide and assist in the movement of SAEDP 171.FIG.\",\n \"24b also illustrates camera 178a and display 178b, which are connected to a processor that generates, based on the video received from the camera, a view of the outside environment when an SAEDP (on the right side of the vehicle) is in the second state.\",\n \"The view of the outside environment is presented to the occupant on the display 178b.\",\n \"Camera and display on the left SAEDP 171, which correspond to camera 178a and display 178b, are not shown in the figure in order to make it clearer; however it is to be understood that such camera and display may be fitted to any relevant moving SAEDP.\",\n \"In one embodiment, the mechanism that moves the SAEDP 171 between the first and second states (referred to as the “SAEDP mechanism”) is similar to a power window regulator that moves an automobile window up and down.\",\n \"As with automobile power windows, the SAEDP regulator may be powered by an electric motor, which may come with the SAEDP regulator as one unit, or as a system that enables the motor or regulator to be replaced separately.\",\n \"The SAEDP mechanism includes a control system, a motor, a gear reduction, a sliding mechanism and the SAEDP, which are usually fixed on the door, but may alternatively be fixed on the roof as disclosed below.\",\n \"The sliding mechanism may have different architectures, such as Bowden type, double Bowden type, cable spiral, or crossed levers.\",\n \"In a first example, the SAEDP mechanism is similar to a double Bowden power window mechanism, in which the SAEDP 171 is fixed on two supports respectively constrained along two rails.\",\n \"The control system drives the motor that wraps two Bowden cables, which move two supports and, consequently, the SAEDP 171.A Bowden cable transmits mechanical force through the movement of an inner cable relative to an outer housing, and in the case of a DC motor, the basic operations of the motor are accomplished by reversing the polarity of its power and ground input.\",\n \"In a second example, the SAEDP mechanism is similar to a gear-drive type power window regulator; in this case, the SAEDP mechanism includes an SAEDP motor to power the mechanism, gear drive and geared arm to move the SAEDP 171 between the first and second states, and an SAEDP holding bracket to hold the SAEDP 171.In a third example, the SAEDP mechanism is similar to a cable type power window regulator; in this case, the SAEDP regulator includes an SAEDP motor that drives a wire cable though a mechanism, a series of pulleys that guide the cable, and a regulator carriage attached to the cable and to the SAEDP 171 and slides on the regulator track.\",\n \"One or more tracks may be mounted vertically inside the door panel that serves as a guide piece when the SAEDP 171 slides up and down.\",\n \"Depending on the design, the setup may have one main regulator track in the center of the door, or have a track on each side of the SAEDP.\",\n \"In a fourth example, the SAEDP regulator is similar to a scissor power window regulator; in this case, a motor operates a gear wheel that raises and lowers the SAEDP 171 by the use of a scissor action of rigid bars.\",\n \"The motor that moves the SAEDP 171 over the sliding mechanism may be any suitable motor, such as a DC electric motor, an AC electric motor, or a pneumatic motor.\",\n \"In one embodiment, the indication that the probability of an imminent collision reaches a threshold is received from the autonomous-driving control system 65 that calculates the probability based on the trajectory of the vehicle and information about the road.\",\n \"Optionally, the information about the road may be received from one of more of the following sources: a sensor mounted to the vehicle, a sensor mounted on a nearby vehicle, a road map, a stationary traffic controller nearby the vehicle, and a central traffic controller that communicates with the vehicle via wireless channel.\",\n \"In one embodiment, the processor 175 is further configured to receive an updated indication that the probability of the imminent collision does not reach a second threshold, and to command the motor to move the SAEDP to the first state.\",\n \"In this embodiment, the second threshold denotes a probability for a collision that is equal or lower than the threshold.\",\n \"FIG.\",\n \"25a and FIG.\",\n \"25b illustrate a motor configured to move a front nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) between first and second states.\",\n \"Some aspects of this disclosure involve an autonomous on-road vehicle that includes an outer nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) mounted to the front side of the vehicle during normal driving, such that the SAEDP is in front of and at eye level of an occupant who sits in a front seat of the vehicle.\",\n \"Additionally, the vehicle includes a camera that is mounted to the vehicle and is configured to take video of the outside environment in front of the occupant, and a computer configured to generate, based on the video, a representation of the outside environment at eye level for the occupant.\",\n \"One non-limiting advantage of the vehicle described above is that it increases the safety of a pedestrian in case of a vehicle-pedestrian collision, without prohibiting the occupant of the vehicle from receiving a frontal view of the outside environment.\",\n \"FIG.\",\n \"26a illustrates one embodiment of an autonomous on-road vehicle that includes outer nontransparent SAEDP 190, which is mounted to the front side of the vehicle during normal driving, such that the SAEDP 190 is in front of and at eye level of an occupant who sits in a front seat of the vehicle.\",\n \"The SAEDP 190 is less stiff than a standard automotive glass window and is designed to absorb some of the crashing energy transmitted to a pedestrian during a pedestrian-vehicle collision.\",\n \"Additionally, the vehicle includes a camera (such as camera 142), which is mounted to the vehicle and is configured to take video of the outside environment in front of the occupant, and a computer (such as computer 143), which is configured to generate, based on the video, a representation of the outside environment at eye level for the occupant.\",\n \"Optionally, the representation is generated from the point of view of the occupant.\",\n \"Optionally, the vehicle includes a display configured to present the representation to the occupant.\",\n \"For example, the display may belong to an HMD worn by the occupant.\",\n \"In another example, the display may be coupled to the compartment of the vehicle, and may be a flexible display.\",\n \"The SAEDP 190 may be implemented utilizing various approaches in different embodiments described herein.\",\n \"In one embodiment, the SAEDP 190 comprises a passive material.\",\n \"Optionally, the SAEDP 190 has thickness greater than at least one of the following thicknesses: 1 cm, 2 cm, 5 cm, 10 cm, 15 cm, and 20 cm.\",\n \"In another embodiment, the SAEDP 190 comprises an automotive airbag configured to inflate in order to protect the pedestrian.\",\n \"FIG.\",\n \"26b illustrates an outer SAEDP 190 that includes two air bags 192 configured to absorb some of the crashing energy transmitted to a pedestrian during a pedestrian-vehicle collision.\",\n \"Optionally, the airbag has a stowed condition and an inflated condition.\",\n \"The airbag is coupled to an inflator configured to inflate the airbag with gas, and the airbag is located, in the stowed condition, at eye level in front of the occupant.\",\n \"In this embodiment, the vehicle further includes an autonomous-driving control system, such as autonomous-driving control system 65, which is configured to calculate a probability of pedestrian-vehicle collision, based on measurements of sensors mounted to the vehicle, and to command the airbag to inflate before the pedestrian head hits the vehicle.\",\n \"In yet another embodiment, the SAEDP 190 comprises a pneumatic pad configured to inflate in order to protect the pedestrian.\",\n \"In this embodiment, the vehicle further includes an autonomous-driving control system, such as autonomous-driving control system 65, which is configured to calculate a probability of pedestrian-vehicle collision, based on measurements of sensors mounted to the vehicle, and to command the pneumatic pad to start inflate at least 0.5 second before the expected time of the collision in order to protect the pedestrian.\",\n \"Optionally, the pneumatic pad is reusable, and can be used multiple times without the need to be repaired.\",\n \"For example, the vehicle comprises a mechanism to deflate and/or stow the pneumatic pad, without requiring its repair and/or replacement.\",\n \"Some aspects of this disclosure involve an autonomous on-road vehicle that includes a window located at eye level of an occupant who sits in a front seat of the vehicle (e.g., a windshield), a reusable nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP), a motor, and a processor.\",\n \"The window enables the occupant to see the outside environment.\",\n \"The motor is configured to move the SAEDP over a sliding mechanism between first and second states multiple times without having to be repaired.\",\n \"In the first state the SAEDP does not block the occupant's eye level frontal view to the outside environment, and in the second state the SAEDP blocks the occupant's eye level frontal view to the outside environment.\",\n \"Additionally, in the second state the SAEDP can absorb some of the crashing energy transmitted to a pedestrian during a pedestrian-vehicle collision.\",\n \"The processor is configured to receive, from an autonomous-driving control system, an indication indicative of whether a probability of an imminent pedestrian-vehicle collision reaches a threshold.\",\n \"Responsive to receiving an indication of an imminent collision (e.g., within less than 2 seconds), the processor is configured to command the motor to move the SAEDP from the first state to the second state.\",\n \"One non-limiting advantage of the vehicle described above is that it increases the safety of a pedestrian in case of a vehicle-pedestrian collision, without prohibiting the occupant of the vehicle from receiving a frontal view of the outside environment during normal driving.\",\n \"FIG.\",\n \"27a and FIG.\",\n \"27b illustrate one embodiment of a motorized external SAEDP 121 that can move between first and second states multiple times.\",\n \"The figures illustrate how the SAEDP 121 can move from the first state (in FIG.\",\n \"27a), in which the SAEDP is stored above the windshield, to the second state (FIG.\",\n \"27b), in which the SAEDP is located in front of the windshield, by having the motor 122 move the SAEDP 121 optionally over a sliding mechanism 123.Additionally, the figures illustrate optional camera 126 that is embedded in the SAEDP 121, and which may provide video to a processor configured to generate a representation of the outside environment when the SAEDP 121 is in the second state.\",\n \"In one embodiment, an autonomous on-road vehicle includes window 120, reusable SAEDP 121, motor 122, and processor 124.The window 120, which is located at eye level of an occupant who sits in a front seat of the vehicle, and which may be a windshield, enables the occupant to see the outside environment.\",\n \"The SAEDP 121 is reusable, i.e., it may be moved multiple times without the need to replace it or repair it after each use.\",\n \"The SAEDP 121 may be implemented utilizing various approaches in different embodiments described herein.\",\n \"In one embodiment, the SAEDP 121 comprises a passive material.\",\n \"Optionally, the SAEDP 121 has thickness greater than at least one of the following thicknesses: 1 cm, 2 cm, 5 cm, 10 cm, 15 cm, and 20 cm.\",\n \"In another embodiment, the SAEDP 121 comprises a pneumatic pad configured to inflate in order to protect the pedestrian.\",\n \"Optionally, the pneumatic pad is reusable, and the processor 124 is configured to command the pneumatic pad to start inflate at least 0.5 second before the expected time of the pedestrian-vehicle collision.\",\n \"The motor 122 is configured to move the SAEDP 121, optionally over a sliding mechanism 123, between first and second states multiple times without having to be repaired.\",\n \"In the first state the SAEDP 121 does not block the occupant's eye level frontal view to the outside environment, and in the second state the SAEDP 121 blocks the occupant's eye level frontal view to the outside environment.\",\n \"When in the second state, the SAEDP 121 is configured to absorb some of the crashing energy transmitted to a pedestrian during a pedestrian-vehicle collision.\",\n \"The SAEDP may be stored above or below the windshield 120.FIG.\",\n \"27a illustrates one embodiment of storing the SAEDP above the windshield.\",\n \"In another embodiment, the SAEDP is stored below the windshield.\",\n \"Optionally, the SAEDP is stored below the windshield in two layers, and shortly before an imminent pedestrian-vehicle collision the first layer stays below the windshield while the second layer is moved by a motor to a location in front of the windshield.\",\n \"Alternatively, the SAEDP is stored below the windshield in a folded manner, and shortly before an imminent pedestrian-vehicle collision the folded SAEDP is stretched by a motor to cover the windshield at least until the occupant's eye level.\",\n \"The processor 124 is configured to receive, from an autonomous-driving control system (such as autonomous-driving control system 65), an indication indicative of whether a probability of an imminent pedestrian-vehicle collision reaches a threshold.\",\n \"Optionally, most of the time the vehicle travels, the processor 124 does not provide an indication that the probability reaches the threshold.\",\n \"Responsive to receiving an indication of an imminent collision (e.g., within less than 2 seconds), the processor 124 is configured to command the motor 122 to move the SAEDP 121 from the first state to the second state.\",\n \"Optionally, the processor 124 is configured to command the motor to start moving the SAEDP 121 to the second state at least 0.2 second, 0.5 second, 1 second, or 2 seconds before the pedestrian-vehicle collision in order to protect the pedestrian.\",\n \"In one example, the vehicle includes a sensor configured to detect the distance and angle between the vehicle and a pedestrian, and the autonomous-driving control system calculates the probability of the imminent pedestrian-vehicle collision based on the data obtained from the sensor, the velocity of vehicle and the possible maneuver.\",\n \"In one embodiment, the processor 124 is further configured to receive an updated indication that indicates the probability of the imminent pedestrian-vehicle collision does not reach a second threshold, and to command the motor 122 to move the SAEDP to the first state.\",\n \"Optionally, the second threshold denotes a probability for a pedestrian-vehicle collision that is equal or lower than the threshold.\",\n \"In one embodiment, the vehicle includes a camera (such as camera 126), which is configured to take video of the outside environment while the SAEDP 121 is in the second state.\",\n \"Additionally, in this embodiment, the vehicle may further include a computer configured to generate, based on the video, a representation of the outside environment, and a display configured to present the representation of the outside environment to the occupant while the SAEDP 121 is in the second state.\",\n \"Optionally, the camera 126 is fixed to the SAEDP 121 from the outer side, and thus moves with the SAEDP 121 when it moves between the first and second states.\",\n \"Optionally, the display is fixed to the SAEDP 121 from the inner side, and thus also moves with the SAEDP 121 when it moves between the first and second states; the occupant can see the display via the window 120 when the SAEDP is in the second state.\",\n \"In an alternative embodiment, the display is physically coupled to the compartment (such as a windshield that also functions as a display) and/or comprised in an HMD worn by the occupant.\",\n \"In addition to, or instead of, moving an SAEDP when a collision is imminent, in some embodiments, an imminent collision may prompt a raise of one or more power windows in the vehicle.\",\n \"This approach is illustrated in the following embodiment.\",\n \"In one embodiment, a safety system for an occupant of an autonomous on-road vehicle includes an automobile power window and an autonomous-driving control system (such as autonomous-driving control system 65).\",\n \"The autonomous-driving control system is configured to calculate probability of an imminent collision based on data received from sensors coupled to the vehicle.\",\n \"Responsive to detecting that the probability reaches a threshold, and at least one second before the expected collision, the autonomous-driving control system commands the power window to rise.\",\n \"In this embodiment, a raised power window provides an improved safety for the occupant of the vehicle during collision compared to a lowered power window.\",\n \"Optionally, responsive to detecting that the probability reaches the threshold, and at least two seconds before the expected collision, the autonomous-driving control system is configured to command the power window to rise.\",\n \"In one embodiment, the vehicle further includes an SAEDP coupled to the power window from the inside (e.g., as illustrated in FIG.\",\n \"24a and FIG.\",\n \"24b).\",\n \"In one embodiment, the power window is nontransparent, and the safety system for the occupant includes a display coupled to the power window from the inside.\",\n \"The display is configured to present to the occupant a video see-trough (VST) of the outside environment that is generated based on a video camera pointed at the outside environment.\",\n \"In another embodiment, the power window is made of a nontransparent material, which is stronger than a standard automotive tempered glass having the same dimensions.\",\n \"In this embodiment, the vehicle further comprises a camera configured to take video of the outside environment (such as camera 178a), and a computer configured to generate a VST to the outside environment based on the video.\",\n \"Optionally, the camera is physically coupled to the power window, such that the camera is raised and lowered with the power window.\",\n \"Additionally or alternatively, the camera may be coupled to an element of the vehicle that is not the power window, such that the camera does not move up and down when the power window is raised and lowered.\",\n \"Optionally, the vehicle further includes a display coupled to the inner side of the power window, such that the display is at eye level when the power window is raised, and below eye level when the power window is lowered; the display is configured to present the VST to the occupant.\",\n \"Optionally, the occupant wears an HMD, and the computer is configured to present the VST to the occupant on the HMD when the power window is raised, and not to present the VST to the occupant on the HMD when the power window is lowered.\",\n \"With autonomous vehicles, it is not necessary for occupants to sit.\",\n \"Some aspects of this disclosure involve autonomous vehicles in which an occupant of the vehicle may lay down.\",\n \"Such a design for an autonomous vehicle has the advantage of enabling a more comfortable position for certain activities (e.g., relaxing or sleeping).\",\n \"Additionally, such a vehicle may be built to be lower than traditional vehicles, which can offer advantages in terms of increased safety (e.g., a lower center of gravity offers better stability) and better vehicle aerodynamics.\",\n \"In order to increase the safety of the occupant, various forms of padding may be used in the compartment of the vehicle.\",\n \"In some embodiments, an autonomous on-road vehicle designed for lying down includes a closed compartment and a mattress, having an average thickness of at least 3 cm, which covers at least 50% of the compartment floor.\",\n \"In the compartment, there is a nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP), having an average thickness of at least 1 cm, which covers at least 50% of the compartment side walls and at least 60% of the compartment front wall during normal driving.\",\n \"Optionally, the SAEDP is supported by a stiff element that resists deformation during a collision in order to reduce compartment intrusion.\",\n \"Additionally, the vehicle includes a camera configured to take video of the outside environment, a computer configured to generate a representation of the outside environment based on the video, and a display configured to present the representation to the occupant.\",\n \"In one embodiment, an autonomous on-road vehicle designed for lying down includes a closed compartment 210, a mattress 211, an SAEDP 212 covering portions of the compartment 210, a camera (e.g., the structure 147 that houses multiple cameras), a computer (e.g., the computer 143), and a display 215.FIG.\",\n \"28 illustrates one embodiment of a vehicle compartment 210 in which an occupant may lay down.\",\n \"In the figure, the occupant is lying down on mattress 211, which covers the floor of the compartment 210, and is watching a movie on the display 215.The SAEDP 212 covers the front, roof, and back of the compartment 210.It is to be noted that the SAEDP 212 also covers portions of the side walls of the compartment 210, however, this is not illustrated to enable a clearer image of the embodiment.\",\n \"The figure also includes an airbag 216, which may be inflated below the SAEDP 212 in order to protect the occupant and restrain his/her movement in the case of a collision.\",\n \"The mattress 211 covers at least 50% of the compartment floor.\",\n \"Optionally, the mattress 211 covers at least 80% of the compartment floor.\",\n \"In one embodiment, the mattress 211 has an average thickness of at least 3 cm.\",\n \"In other embodiments, the average thickness of the mattress 211 is greater than at least one of the following thicknesses: 5 cm, 7 cm, 10 cm, 20 cm, and 30 cm.\",\n \"The SAEDP 212 is a nontransparent SAEDP, having an average thickness of at least 1 cm.\",\n \"Optionally, the SAEDP 212 covers at least 50% of the compartment side walls and at least 60% of the compartment front wall during normal driving.\",\n \"In one embodiment, the average thickness of the SAEDP 212 is greater than at least one of the following thicknesses: 2 cm, 3 cm, 5 cm, 10 cm, 15 cm, and 20 cm.\",\n \"In another embodiment, the SAEDP 212 covers at least 80% of the compartment side walls and at least 80% of the compartment front wall.\",\n \"In yet another embodiment, the SAEDP covers at least 50% of the compartment roof.\",\n \"In still another embodiment, the mattress and the SAEDP cover essentially the entire compartment interior.\",\n \"In addition to the SAEDP 212, in some embodiments additional measures may be employed in order to improve the safety of the occupant.\",\n \"In one embodiment, the vehicle includes an automotive airbag configured to deploy in front of the SAEDP 212 in order to protect the occupant, in addition to the SAEDP 212, against hitting the inner side of the vehicle compartment during a collision.\",\n \"It is noted that the meaning that the airbag deploys in front of the SAEDP is that the airbag deploys towards the inner side of the compartment.\",\n \"Optionally, the airbag has a stowed condition and an inflated condition, and the airbag is coupled to an inflator configured to inflate the airbag with gas upon computing a predetermined impact severity.\",\n \"The stowed airbags may be stored in various positions, such as stored essentially in the middle of the front wall, stored essentially in the middle of the rear wall, stored in the side walls (possibly two or more horizontally spaced airbags), and stored in the roof (possibly one or more airbags towards the front of the compartment and one or more airbags towards the rear of the compartment).\",\n \"In some embodiments, various additional safety measures may be utilized to improve the safety of the occupant while traveling, such as a sleeping net and/or a safety belt, as described for example in U.S. Pat.\",\n \"Nos.\",\n \"5,536,042 and 5,375,879.Stiff element 213 is configured to support the SAEDP 212 and to resist deformation during a collision in order to reduce compartment intrusion.\",\n \"Part of the stiff element 213 is located, during normal driving, at eye level between the SAEDP 212 and the outside environment.\",\n \"Optionally, the stiff element covers, from the outside, more than 80% of the SAEDP on the compartment side walls.\",\n \"Optionally, the vehicle also includes a crumple zone located at eye level between the stiff element 213 and the outside environment.\",\n \"In another embodiment, the vehicle includes a pneumatic pad configured to inflate in order to protect the occupant, in addition to the SAEDP 212, against hitting the inner side of the vehicle compartment during a collision.\",\n \"Optionally, the pneumatic pad is configured to deploy in front of the SAEDP 212 towards the inner side of the compartment.\",\n \"Alternatively, the pneumatic pad is located between the SAEDP 212 and the stiff element 213, and is configured to deploy behind the SAEDP 212.The pneumatic pad may be mounted to various locations, such as mounted to the front wall, mounted to the rear wall, mounted to the side walls, and/or mounted to the roof.\",\n \"The camera is configured to take video of the outside environment.\",\n \"The computer is configured to generate a representation of the outside environment based on the video.\",\n \"Optionally, the representation is generated from the point of view of the occupant.\",\n \"The display 215 is configured to present the representation to the occupant.\",\n \"In one embodiment, the display 215 is comprised in an HMD, and the vehicle further comprises a communication system configured to transmit the representation to the HMD.\",\n \"In another embodiment, the display 215 is physically coupled to at least one of the SAEDP 212 and the stiff element 213 at eye level of the occupant.\",\n \"Optionally, the display 215 is a flexible display.\",\n \"For example, the display 215 may be a flexible display that is based on at least one of the following technologies and their variants: OLED, organic thin film transistors (OTFT), electronic paper (e-paper), rollable display, and flexible AMOLED.\",\n \"Optionally, the display 215 is flexible enough such that it does not degrade the performance of the SAEDP by more than 20% during a collision.\",\n \"Having a vehicle compartment that is designed to allow an occupant to lay down comfortably can be done using various compartment designs, which may be different from the designs used in standard vehicles, in which occupants primarily sit up.\",\n \"In one example, the vehicle does not have an automotive seat with a backrest and safety belt, which enables the occupant to sit straight in the front two thirds of the compartment.\",\n \"In another example, the vehicle is designed for a single occupant, and the average distance between the mattress and the compartment roof is below 80 cm.\",\n \"In still another example, the vehicle is designed for a single occupant, and the average distance between the mattress and the compartment roof is below 70 cm.\",\n \"In still another example, the vehicle is designed for a single occupant, and the average distance of the compartment roof from the road is less than 1 meter.\",\n \"And in yet another example the vehicle is designed for a single occupant, and the average distance of the compartment roof from the road is less than 80 cm.\",\n \"It is to be noted that the use of the terms “floor”, “roof”, “side walls”, and “front wall” with respect to the compartment are to be viewed in their common meaning when one considers the compartment to be a mostly convex hull in 3D, such as having a shape that resembles a cuboid.\",\n \"Thus, for example, an occupant whose face faces forward, will see the front wall ahead, the floor when looking below, the roof when looking above, and a side wall when looking to one of the sides (left or right).\",\n \"In embodiments that do not resemble cuboids, alternative definitions for these terms may be used based on the relative region (in 3D space) that each of the portions of the compartment occupy.\",\n \"For example, the floor of the compartment may be considered to be any portion of the compartment which is below at least 80% of the volume of the compartment.\",\n \"Similarly, the roof may be any portion of the compartment that is above at least 80% of the volume of the compartment.\",\n \"The front wall may be any portion of the compartment that is ahead of at least 80% of the volume of the compartment, etc.\",\n \"Note that using this alternative definitions, some portions of the compartment may be characterized as belonging to two different regions (e.g., the front wall and the roof).\",\n \"Some aspects of this disclosure involve an autonomous on-road vehicle that includes a compartment having a large mirroring element located in front of an occupant who sits in a front seat of the compartment.\",\n \"Optionally, the mirroring element has height and width exceeding 25×25 cm, such that it covers a square that is at least those dimensions.\",\n \"Optionally, the mirroring element captures a region corresponding to at least 10×10 degrees, including a region spanning from the horizon to 10° below the horizon, of the occupant's forward field of view during normal driving.\",\n \"Additionally, the mirroring element provides an effect of reflecting more than 25% of the light arriving from the occupant's direction.\",\n \"In some embodiments, the vehicle has an advantage that it can increase the perceived compartment volume, which can make travelling in the vehicle more pleasurable for some people.\",\n \"FIG.\",\n \"29 illustrates one embodiment of a vehicle having a front mirroring element.\",\n \"The figure illustrates how the occupant 222 can see her reflection 223 in the mirroring element 220.In one embodiment, the mirroring element 220 is located in front of an occupant who sits in a front seat of the vehicle.\",\n \"The mirroring element 220 provides an effect of reflecting more than 25% of the light arriving from the occupant's direction.\",\n \"Optionally, the mirroring element 220 provides an effect of reflecting more than at least one of 50%, 80%, and 90% of the light arriving from the occupant's direction.\",\n \"Optionally, the mirroring element 220 increases the volume of the vehicle compartment as perceived by the occupant due to the reflection effect.\",\n \"In one embodiment, the mirroring element 220 has height and width exceeding 25×25 cm, such that it covers a square that is at least those dimensions.\",\n \"Optionally, the mirroring element 220 captures a region corresponding to at least 10×10 degrees, including a region spanning from the horizon to 10° below the horizon, of the occupant's forward field of view during normal driving.\",\n \"Optionally, the height and width of the mirroring element 220 is above 50×40 cm, and the mirroring element captures above 30×30 degrees of the occupant's field of view, including a region spanning from the horizon to 30° below the horizon.\",\n \"Optionally, the mirroring element 220 covers more than 25% of the area where a conventional windshield of a normal non-autonomous on-road vehicle in year 2016 is expected to be located.\",\n \"The mirroring element 220 may be implemented in different ways, in different embodiments.\",\n \"In one embodiment, the mirroring element 220 comprises an optical mirror that is essentially flat and perpendicular to the ground.\",\n \"In this embodiment, most of the effect of reflecting is generated by the optical mirror.\",\n \"In one example, an optical mirror that is essentially flat and perpendicular to the ground refers to an optical mirror having a radius of curvature greater than a meter and a deviation below ±30° from the perpendicular to the ground.\",\n \"In another embodiment, the mirroring element 220 comprises a Fresnel type optical reflector comprising many reflecting prisms.\",\n \"In this embodiment, the Fresnel type optical reflector is not flat, but the reflecting prisms are arranged in angles that reflect the light from the occupant such as to imitate a flat mirror.\",\n \"In one embodiment, the mirroring element 220 comprises an electronic display that operates based on a camera 221 configured to take video of the occupant 222, and a computer 224 configured to generate a digital representation of the occupant 223 based on the video of the occupant.\",\n \"In this case, most of the effect of reflecting is generated by light emitted by the electronic display (which is the output of the video of the occupant as generated by the computer 224).\",\n \"Due to the close proximity between the at least one camera 221 and the occupant, it may be necessary to stitch the reflecting effect of a large area from multiple cameras that capture the occupant from different angles.\",\n \"In one example, the camera 221 comprises first and second cameras, located to the right and left of the occupant, respectively.\",\n \"In another example, the camera 221 comprises first and second cameras, located above the level of the occupant's nose and below the level of the occupant's collarbone, respectively, and less than 80 cm away from the occupant.\",\n \"In still another embodiment, the effect of reflecting is achieved by a digital mirror that comprises multiple cameras embedded within the digital mirror and configured to take images of the occupant, and multiple light emitting pixels configured to emit light rays that generate the effect of reflecting.\",\n \"In one embodiment, the mirroring element 220 comprises an electronic display, and the vehicle further includes a camera configured to take video of the outside environment in front of the occupant, and a computer configured to generate, based on the video, a representation of the outside environment in front of the occupant at eye level, for displaying on the mirroring element 220.In addition to the effect of reflecting, in some embodiments the mirroring element 220 may also be configured to operate in a second state in which it provides an effect of reflecting less than 20% of the light arriving from the occupant's direction, and to present to the occupant the representation of the outside environment.\",\n \"Here, presenting the representation may imitate a transparent windshield to the outside environment.\",\n \"The vehicle may also include, in some embodiments, a display configured to present to the occupant, at eye level in front of the occupant, the representation of the outside environment instead of, or in addition to, the effect of reflecting.\",\n \"Optionally, the vehicle may include a user interface configured to enable the occupant to switch between seeing the effect of reflecting and seeing the representation of the outside environment.\",\n \"In one example, the display is comprised in a head-mounted display (HMD).\",\n \"In another example, the display is mechanically coupled to the compartment, and/or the mirroring element comprises the display.\",\n \"As described above, the effect of reflecting light that comes from the direction of the occupant may be obtained, in some embodiments, utilizing an HMD.\",\n \"The following is a more detailed example of such an embodiment.\",\n \"In one embodiment, an autonomous on-road vehicle includes a compartment comprising a front seat, a camera, a computer, a communication module, and an HMD.\",\n \"The camera is physically coupled to the vehicle, configured to take images of an occupant who sits in the front seat.\",\n \"The computer is configured to generate, based on the images, a video that shows a mirror effect.\",\n \"Herein, the “mirror effect” involves presenting the occupant with an image that is similar to an image that the occupant would see had there been an actual mirror in front of the occupant.\",\n \"Optionally, the system enables the occupant to have control on the synthetic mirror effect, such as control on the distance between the occupant and her image, and/or control on the width of the image.\",\n \"The communication module is configured to transmit the video to a head-mounted display (HMD) worn by the occupant, and the HMD is configured to present the video to the occupant, such that the occupant sees a representation of his or her reflection when looking forward at eye level.\",\n \"Optionally, the HMD is selected from the group comprising: a virtual reality headset, an augmented reality headset, and mixed reality headset.\",\n \"Optionally, the video presented to the occupant captures at least 30×30 degrees of the occupant's field of view, spanning at least from the horizon to 30° below the horizon.\",\n \"In one embodiment, the vehicle described above further includes a second camera configured to take a second set of images of the outside environment in front of the occupant.\",\n \"In this embodiment, the computer is further configured to generate a representation of the outside environment based on the second set of images, and the HMD is configured to present the representation of the outside environment instead of the video that shows the mirror effect or in addition to the video that shows the mirror effect.\",\n \"In one embodiment, the vehicle described above may include multiple cameras that capture images that are utilized by the computer to generate the video that shows the mirror effect.\",\n \"In one example, the vehicle comprises at least first and second cameras, which are located to the right and left of the occupant, respectively.\",\n \"In another example, the vehicle comprises at least first and second cameras, located above the level of the occupant's nose and below the level of the occupant's collarbone, respectively, and which are less than 80 cm away from the occupant.\",\n \"Some aspects of this disclosure involve utilizing one or more nontransparent side beams in order to help protect the occupant in a case of a collision.\",\n \"The one or more side beams are stiffer than automotive laminated glass.\",\n \"In one example, a side beam comprises a high tensile steel pipe and pressed material.\",\n \"In another example, a side beam comprises an aluminum extruded shape.\",\n \"In one embodiment, an autonomous on-road vehicle that weighs less than 1500 kg without batteries includes a nontransparent side beam, which is stiffer than automotive laminated glass, and is located during normal driving to the left and at eye level of an occupant who sits in a front seat.\",\n \"The vehicle also includes a camera configured to take video of the outside environment to the left of the occupant, and a computer configured to generate for the occupant, based on the video, a representation of the outside environment to the left of the occupant at eye level.\",\n \"Optionally, the representation is presented to the occupant using a display.\",\n \"In one example, the display is comprised in a head-mounted display (HMD), and the vehicle further comprises a communication system configured to transmit the representation to the HMD.\",\n \"In another example, the display is coupled to the inner side of the compartment.\",\n \"The following is a description of an embodiment of a vehicle in which one or more side beams may be utilized to help protect the left side of a vehicle (and an occupant therein).\",\n \"In one embodiment, an autonomous on-road vehicle includes a nontransparent side beam, a camera (e.g., the camera 161), and a computer (e.g., the computer 143).\",\n \"Optionally, the vehicle weighs less than 1500 kg without batteries.\",\n \"The nontransparent side beam, which is stiffer than automotive laminated glass, is located, during normal driving, at eye level to the left of an occupant who sits in a front seat of the vehicle.\",\n \"Optionally, the side beam is at least 60 cm long and at least 1 cm wide (herein “cm” refers to centimeters).\",\n \"In one example, the side beam comprises a high tensile steel pipe and pressed material.\",\n \"In another example, the side beam comprises an aluminum extruded shape.\",\n \"The camera configured to take video of the outside environment to the left of the occupant.\",\n \"The computer is configured to generate for the occupant, based on the video, a representation of the outside environment to the left of the occupant at eye level.\",\n \"Optionally, the representation is generated from the point of view of the occupant, and the vehicle further includes a display configured to present the representation to the occupant.\",\n \"In one example, the display is comprised in a head-mounted display (HMD), and the vehicle further comprises a communication system configured to transmit the representation to the HMD.\",\n \"In another example, the display is coupled to the inner side of the compartment.\",\n \"In some embodiments, a plurality of beams, which may be similar to the side beam described above, may be located in the region of the left side of the vehicle.\",\n \"It is to be noted that the plurality of beams may not necessarily all have the same dimensions or be made of the same exact materials.\",\n \"Optionally, the plurality of beams may be connected in various ways in order to form a structure that can better resist compartment deforming in the case of a collision.\",\n \"For example, in one embodiment, the vehicle includes an additional side beam that is not parallel to the side beam and crosses it to form an “X” shaped structure.\",\n \"Herein, an “X” shaped structure refers to any structure of two nonparallel beams that cross, and the two do not necessarily form a symmetric “X” (e.g., a symmetric “X” may be obtained when the two beams are of equal length and cross at their centers).\",\n \"This structure is illustrated in FIG.\",\n \"30a where beams 231 and 232 cross to form an “X” shape structure.\",\n \"It is to be noted that the beam 231 is at eye level (i.e., at least a portion of the beam 231 is at the same height as a typical occupant's eyes).\",\n \"FIG.\",\n \"30a illustrates one example of a configuration of a plurality of beams located in the left side of the vehicle.\",\n \"Different designs of vehicles may benefit from utilizing one or more sides beam as described above.\",\n \"In one embodiment, the side beam is embedded in a movable structure that changes its location with respect to the vehicle compartment.\",\n \"For example, the side beam may be part of a left door of the vehicle.\",\n \"In another embodiment, the side beam is embedded in the vehicle compartment itself and does not change its location with respect to the rest of the compartment.\",\n \"For example, the side beam may be placed in a compartment wall to the left of the occupant.\",\n \"In order to better protect the occupant from injury due to hitting the head against the side of the vehicle, in some embodiments, the vehicle may comprise a nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) located at eye level between the side beam and the occupant.\",\n \"The SAEDP is less stiff than a standard automotive glass window.\",\n \"In one example, the SAEDP comprises a passive material.\",\n \"In another example, the SAEDP includes an airbag.\",\n \"And in still another example, the SAEDP includes a pneumatic pad.\",\n \"Optionally, the vehicle includes a display on which the representation of the outside environment may be presented to the occupant.\",\n \"Optionally, the display is supported by the SAEDP and/or the side beam.\",\n \"Optionally, the display is a flexible display.\",\n \"In a similar fashion to the utilization of beams on the left side of the vehicle, in some embodiments, one or more beams may be used to help protect the occupant's right side.\",\n \"For example, in one embodiment, the vehicle includes a second side beam, located at eye level to the right of the occupant, and a second camera configured to take video of the outside environment to the right of the occupant.\",\n \"In this embodiment, the computer is further configured to generate a second representation of the outside environment to the right of the occupant.\",\n \"Some aspects of this disclosure involve utilizing one or more nontransparent beams in order to help protect the occupant in a case of a collision.\",\n \"The one or more beams are stiffer than automotive laminated glass.\",\n \"In one example, a nontransparent beam comprises a high tensile steel pipe and pressed material.\",\n \"In another example, a nontransparent beam comprises an aluminum extruded shape.\",\n \"In one embodiment, an autonomous on-road vehicle that weighs less than 1500 kg without batteries includes a nontransparent beam, which is stiffer than automotive laminated glass, and is fixed at eye level in front of an occupant who sits in a front seat of the vehicle during normal driving.\",\n \"The vehicle also includes a camera configured to take video of the outside environment in front of the occupant, and a computer configured to generate for the occupant, based on the video, a representation of the outside environment in front of the occupant at eye level.\",\n \"Optionally, the representation is presented to the occupant using a display.\",\n \"In one example, the display is comprised in a head-mounted display (HMD), and the vehicle further comprises a communication system configured to transmit the representation to the HMD.\",\n \"In another example, the display is coupled to the inner side of the compartment.\",\n \"The following is a description of an embodiment of a vehicle in which one or more nontransparent beams may be utilized to help protect the vehicle's front (and an occupant therein).\",\n \"In one embodiment, an autonomous on-road vehicle includes a nontransparent beam, a camera (e.g., the camera 142), and a computer (e.g., the computer 143).\",\n \"Optionally, the vehicle weighs less than 1500 kg without batteries.\",\n \"The nontransparent beam, which is stiffer than automotive laminated glass, is located, during normal driving, at eye level in front an occupant who sits in a front seat of the vehicle.\",\n \"Optionally, the nontransparent beam is at least 60 cm long and at least 1 cm wide (herein “cm” refers to centimeters).\",\n \"In one example, the nontransparent beam comprises a high tensile steel pipe and pressed material.\",\n \"In another example, the nontransparent beam comprises an aluminum extruded shape.\",\n \"The camera configured to take video of the outside environment in front of the occupant.\",\n \"The computer is configured to generate for the occupant, based on the video, a representation of the outside environment in front of the occupant at eye level.\",\n \"Optionally, the representation is generated from the point of view of the occupant, and the vehicle further includes a display configured to present the representation to the occupant.\",\n \"In one example, the display is comprised in a head-mounted display (HMD), and the vehicle further comprises a communication system configured to transmit the representation to the HMD.\",\n \"In another example, the display is coupled to the inner side of the compartment.\",\n \"In some embodiments, a plurality of beams, which may be similar to the nontransparent beam described above, may be located in the front of the vehicle.\",\n \"It is to be noted that the plurality of beams may not necessarily all have the same dimensions or be made of the same exact materials.\",\n \"Optionally, the plurality of beams may be connected in various ways in order to form a structure that can better resist compartment deformation in the case of a collision.\",\n \"For example, in one embodiment, the vehicle includes an additional nontransparent beam that is not parallel to the nontransparent beam and crosses it to form an “X” shaped structure.\",\n \"This structure is illustrated in FIG.\",\n \"30b where beams 235 and 236 cross to form an “X” shape structure.\",\n \"Both of the beams 235 and 236 are at eye level (i.e., at least a portion of each beam is at the same height as a typical occupant's eyes).\",\n \"FIG.\",\n \"30b illustrates one example of a configuration of a plurality of beams located in the front of the vehicle.\",\n \"Different designs of vehicles may benefit from utilizing one or more nontransparent beam as described above.\",\n \"In one embodiment, the nontransparent beam is embedded in a movable structure that changes its location with respect to the vehicle compartment.\",\n \"For example, the nontransparent beam may be part of a front door through which the occupant may enter the vehicle.\",\n \"In another embodiment, the nontransparent beam is embedded in the vehicle compartment itself and does not change its location with respect to the rest of the compartment.\",\n \"For example, the nontransparent beam may be placed in a compartment wall in front of the occupant.\",\n \"In order to better protect the occupant from injury (e.g., during a collision), in some embodiments, the vehicle may comprise a nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) located at eye level between the nontransparent beam and the occupant.\",\n \"The SAEDP is less stiff than a standard automotive glass window.\",\n \"In one example, the SAEDP comprises a passive material.\",\n \"In another example, the SAEDP includes an airbag.\",\n \"And in still another example, the SAEDP includes a pneumatic pad.\",\n \"Optionally, the vehicle includes a display on which the representation of the outside environment may be presented to the occupant.\",\n \"Optionally, the display is coupled to the inner side of the compartment.\",\n \"Optionally, the display is a flexible display.\",\n \"Various embodiments described herein include a processor and/or a computer.\",\n \"For example, the autonomous-driving control system may be implemented using a computer and generation of a representation of the outside environment is done using a processor or a computer.\",\n \"The following are some examples of various types of computers and/or processors that may be utilized in some of the embodiments described herein.\",\n \"FIG.\",\n \"31a and FIG.\",\n \"31b are schematic illustrations of possible embodiments for computers (400, 410) that are able to realize one or more of the embodiments discussed herein.\",\n \"The computer (400, 410) may be implemented in various ways, such as, but not limited to, a server, a client, a personal computer, a network device, a handheld device (e.g., a smartphone), and/or any other computer form capable of executing a set of computer instructions.\",\n \"The computer 400 includes one or more of the following components: processor 401, memory 402, computer readable medium 403, user interface 404, communication interface 405, and bus 406.In one example, the processor 401 may include one or more of the following components: a general-purpose processing device, a microprocessor, a central processing unit, a complex instruction set computing (CISC) microprocessor, a reduced instruction set computing (RISC) microprocessor, a very long instruction word (VLIW) microprocessor, a special-purpose processing device, an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), a digital signal processor (DSP), a distributed processing entity, and/or a network processor.\",\n \"Continuing the example, the memory 402 may include one or more of the following memory components: CPU cache, main memory, read-only memory (ROM), dynamic random access memory (DRAM) such as synchronous DRAM (SDRAM), flash memory, static random access memory (SRAM), and/or a data storage device.\",\n \"The processor 401 and the one or more memory components may communicate with each other via a bus, such as bus 406.The computer 410 includes one or more of the following components: processor 411, memory 412, and communication interface 413.In one example, the processor 411 may include one or more of the following components: a general-purpose processing device, a microprocessor, a central processing unit, a complex instruction set computing (CISC) microprocessor, a reduced instruction set computing (RISC) microprocessor, a very long instruction word (VLIW) microprocessor, a special-purpose processing device, an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), a digital signal processor (DSP), a distributed processing entity, and/or a network processor.\",\n \"Continuing the example, the memory 412 may include one or more of the following memory components: CPU cache, main memory, read-only memory (ROM), dynamic random access memory (DRAM) such as synchronous DRAM (SDRAM), flash memory, static random access memory (SRAM), and/or a data storage device Still continuing the examples, the communication interface (405,413) may include one or more components for connecting to one or more of the following: an inter-vehicle network, Ethernet, intranet, the Internet, a fiber communication network, a wired communication network, and/or a wireless communication network.\",\n \"Optionally, the communication interface (405,413) is used to connect with the network 408.Additionally or alternatively, the communication interface 405 may be used to connect to other networks and/or other communication interfaces.\",\n \"Still continuing the example, the user interface 404 may include one or more of the following components: (i) an image generation device, such as a video display, an augmented reality system, a virtual reality system, and/or a mixed reality system, (ii) an audio generation device, such as one or more speakers, (iii) an input device, such as a keyboard, a mouse, an electronic pen, a gesture based input device that may be active or passive, and/or a brain-computer interface.\",\n \"It is to be noted that when a processor (computer) is disclosed in one embodiment, the scope of the embodiment is intended to also cover the use of multiple processors (computers).\",\n \"Additionally, in some embodiments, a processor and/or computer disclosed in an embodiment may be part of the vehicle, while in other embodiments, the processor and/or computer may be separate of the vehicle.\",\n \"For example, the processor and/or computer may be in a device carried by the occupant and/or remote of the vehicle (e.g., a server).\",\n \"As used herein, references to “one embodiment” (and its variations) mean that the feature being referred to may be included in at least one embodiment of the invention.\",\n \"Moreover, separate references to “one embodiment”, “some embodiments”, “another embodiment”, “still another embodiment”, etc., may refer to the same embodiment, may illustrate different aspects of an embodiment, and/or may refer to different embodiments.\",\n \"Some embodiments may be described using the verb “indicating”, the adjective “indicative”, and/or using variations thereof.\",\n \"Herein, sentences in the form of “X is indicative of Y” mean that X includes information correlated with Y, up to the case where X equals Y. Additionally, sentences in the form of “provide/receive an indication indicating whether X happened” refer herein to any indication method, including but not limited to: sending/receiving a signal when X happened and not sending/receiving a signal when X did not happen, not sending/receiving a signal when X happened and sending/receiving a signal when X did not happen, and/or sending/receiving a first signal when X happened and sending/receiving a second signal X did not happen.\",\n \"Herein, “most” of something is defined herein as above 51% of the something (including 100% of the something).\",\n \"A “portion” of something refers herein to 0.1% to 100% of the something (including 100% of the something).\",\n \"Sentences of the form “a portion of an area” refer herein to 0.1% to 100% percent of the area.\",\n \"As used herein, the terms “comprises,” “comprising,” “includes,” “including,” “has,” “having”, or any other variation thereof, indicate an open claim language that does not exclude additional limitations.\",\n \"The “a” or “an” is employed to describe one or more, and the singular also includes the plural unless it is obvious that it is meant otherwise.\",\n \"Certain features of some of the embodiments, which may have been, for clarity, described in the context of separate embodiments, may also be provided in various combinations in a single embodiment.\",\n \"Conversely, various features of some of the embodiments, which may have been, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-combination.\",\n \"Embodiments described in conjunction with specific examples are presented by way of example, and not limitation.\",\n \"Moreover, it is evident that many alternatives, modifications, and variations will be apparent to those skilled in the art.\",\n \"It is to be understood that other embodiments may be utilized and structural changes may be made without departing from the scope of the appended claims and their equivalents.\"\n ]\n]"},"source":{"kind":"string","value":"Patent_15871970"}}},{"rowIdx":4493968,"cells":{"text":{"kind":"list like","value":[["Press-On Pedicle Screw Assembly","A tulip assembly configured to be coupled to a screw head having a first diameter includes a housing, wherein the housing defines an inner diameter configured to engage the first diameter of the screw head.","The exemplary inner diameter of the housing being smaller than the first diameter of the screw head."],["1.An implant assembly configured to be coupled to and extend between heads of two pedicle screws, each pedicle screw comprising a head having a head diameter and an elongate threaded portion coupled to and extending from the head, the implant assembly comprising: a first tulip assembly having a first cylindrical bore extending into the first tulip assembly, the first cylindrical bore having a first inner diameter defined by an inner wall of the first tulip assembly, the first inner diameter being smaller than the head diameter of the pedicle screws; a second tulip assembly having a first cylindrical bore extending into the second tulip assembly, the first cylindrical bore having a first inner diameter defined by an inner wall of the second tulip assembly, the first inner diameter being smaller than the head diameter of the pedicle screws; and a rod permanently connected to and extending between the first tulip assembly and the second tulip assembly.","2.The implant assembly of claim 1, wherein the first tulip assembly, the second tulip assembly, and the rod are permanently coupled prior to coupling of the implant assembly to the two pedicle screws.","3.The implant assembly of claim 1, wherein the first tulip assembly, the second tulip assembly, and the rod are unitarily formed from a single piece of material.","4.The implant assembly of claim 1, wherein each of the first tulip assembly and the second tulip assembly further comprise a second cylindrical bore comprising: an axis of symmetry shared with an axis of symmetry of the first cylindrical bore of the respective tulip assembly; and an inner diameter smaller than the first inner diameter; wherein the second cylindrical bore extends into the housing from an internal end of the first cylindrical bore.","5.The implant assembly of claim 1, wherein the first cylindrical bores of the first and second tulip assemblies permit head-first introduction of the head of one of the pedicle screws into the first cylindrical bore until a section having the head diameter is entirely within the first cylindrical bore, thereby creating a compression fit between the inner wall and the head of the pedicle screw within the first cylindrical bore due to the head diameter of the pedicle screw being larger than the inner diameter of the first cylindrical bore.","6.The implant assembly of claim 5, wherein the compression fit between the inner wall and the head of the pedicle screw is capable of withstanding at least 200 pounds of removal force between the tulip assembly and the pedicle screw along an axis of the bore without relative movement of the screw head along the first cylindrical bore.","7.The implant assembly of claim 5, wherein each tulip assembly is adapted to permit head-first introduction of the head of the pedicle screw into the first cylindrical bore to the point of creating the compression fit while at least a portion of the elongate threaded portion of the pedicle screw is embedded in bone.","8.The implant assembly of claim 1, wherein the implant assembly further comprises two pedicle screws and wherein the head of each pedicle screw comprises a truncated spherical shape.","9.The implant assembly of claim 1, wherein the implant assembly comprises a material selected from the group consisting of a titanium alloy, a cobalt chrome alloy, and a nickel titanium alloy.","10.An implant assembly comprising: a pedicle screw comprising a head having a head diameter and an elongate threaded portion coupled to and extending from the head; and a tulip assembly comprising: a housing defining an engagement orifice and a bore extending into the housing from the engagement orifice, the engagement orifice and the bore having a fixed shape and an inner diameter that is smaller than the head diameter of the pedicle screw; wherein head-first introduction of the head of the pedicle screw through the engagement orifice and into the bore with the screw head in the bore creates a compression fit between the housing and the head of the pedicle screw due to the head diameter of the pedicle screw being larger than the inner diameter of the engagement orifice and the bore.","11.The implant assembly of claim 10, wherein the compression fit between the housing and the head of the pedicle screw is capable of withstanding at least 200 pounds of removal force between the tulip assembly and the pedicle screw along an axis of the bore without relative movement of the screw head along the bore.","12.The implant assembly of claim 10, wherein the bore is a first bore and the inner diameter is a first inner diameter, and wherein the tulip assembly further comprises a second bore comprising: an axis of symmetry parallel to an axis of symmetry of the first bore; and an inner diameter smaller than the first inner diameter; wherein the second bore extends into the housing from an internal end of the first bore.","13.The implant assembly of claim 10, wherein the engagement orifice is circular and wherein the inner wall of the housing defines a cylindrical portion of the bore extending into the housing from the engagement orifice.","14.The implant assembly of claim 10, wherein the head of the pedicle screw comprises a truncated spherical shape.","15.The implant assembly of claim 10, wherein the assembly comprises two tulip assemblies, the tulip assemblies each being connected to a rod extending between the tulip assemblies.","16.The implant assembly of claim 15, wherein the rod is permanently coupled to the two tulip assemblies prior to implantation of the implant assembly by introduction of a pedicle screw into the cylindrical bore of either tulip assembly.","17.The implant assembly of claim 10, wherein said housing comprises a material selected from the group consisting of a titanium alloy, a cobalt chrome alloy, and a nickel titanium alloy.","18.A method for affixing a press-on pedicle screw assembly to a spine, comprising: inserting a first pedicle screw having a head portion with a head diameter into a first desired bone of a patient's spine; inserting a second pedicle screw having a head portion with a head diameter into a second desired bone of a patient's spine; after the first and second pedicle screws are inserted into the bones of the patient's spine, guiding a tulip assembly having a housing defining an engagement orifice and a bore extending into the housing from the engagement orifice, the engagement orifice and the bore having a fixed shape and an inner diameter defined by an inner wall of the housing that is smaller than the head diameter of the pedicle screws, until the engagement orifice is proximate the head portion of the first pedicle screw; and applying a force between the first pedicle screw and the tulip assembly whereby the head portion of the pedicle screw is drawn into the bore of the tulip assembly, thereby creating a compression fit between the inner wall of the housing and the head of the pedicle screw due to the head diameter of the pedicle screw being larger than the inner diameter of the engagement orifice and the bore.","19.The method as recited in claim 18, wherein the tulip assembly is a first tulip assembly of an implant assembly comprising two tulip assemblies, the method further comprising: positioning a second tulip assembly with its engagement orifice proximate the head portion of the second pedicle screw; and applying a force between the second pedicle screw and the second tulip assembly whereby the head portion of the second pedicle screw is drawn into the bore of the second tulip assembly, thereby creating a compression fit between the inner wall of the housing and the head of the second pedicle screw due to the head diameter of the second pedicle screw being larger than the inner diameter of the engagement orifice and the bore.","20.The method as recited in claim 19, further comprising connecting the two tulip assemblies together via a rod before engaging either tulip assembly to either pedicle screw via the compression fit."],[" 2.Background and Related Art 2 .","Background and Related Art The use of bone stabilization/fixation devices to align or position bones is well established.","Furthermore, the use of spinal bone stabilization/fixation devices to align or position specific vertebrae or a region of the spine is well established.","Typically such devices for the spine utilize a spinal fixation element, comprised of a relatively rigid member such as a plate or a rod that is used as a coupler between adjacent vertebrae.","Such a spinal fixation element can effect a rigid positioning of adjacent vertebrae when attached to the pedicle portion of the vertebrae using pedicle bone anchorage screws.","Once the coupled vertebrae are spatially fixed in position, procedures can be performed, healing can proceed, or spinal fusion may take place.","Spinal fixation elements may be introduced to stabilize the various vertebrae of the spine.","Some devices for this purpose are designed to be attached directly to the spine, but the generally invasive nature of standard paraspinal approach used to implant these devices may pose drawbacks.","For example, muscle disruption and blood loss may result from standard paraspinal implantation approaches.","Conventional pedicle screw systems and even more recently designed pedicle screw systems also have several drawbacks.","Some of these pedicle screw systems are rather large and bulky, which may result in more tissue damage in and around the surgical site when the pedicle screw system is installed during surgery.","The prior art pedicle screw systems have a rod-receiving device that is pre-operatively coupled or attached to the pedicle screw.","In addition, some of the prior art pedicle screw systems include numerous components that must all be carefully assembled together.","Further, traditional pedicle screw systems are pre-operatively assembled, which makes these systems more difficult to install and maneuver in a spinal operation where MIS techniques are used."],[" BRIEF SUMMARY OF THE INVENTION A tulip assembly configured to be coupled to a screw head having a first diameter includes a housing, wherein the housing defines an inner diameter configured to engage the first diameter of the screw head.","The exemplary inner diameter of the housing being smaller than the first diameter of the screw head."],["CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of U.S. patent application Ser.","No.","11/952,709 filed Dec. 7, 2007 which claims the benefit under 35 U.S.C.§ 119(e) of U.S.","Provisional Patent Application No: 60/873,698, filed Dec. 7, 2006, titled “Press on Screw Tulip,” which applications are incorporated herein by reference in their entirety.","TECHNICAL FIELD 1.Field of the Invention The present exemplary system and method relates to medical devices.","More particularly, the present exemplary system and method relates to percutaneous orthopedic rod placement devices.","2.Background and Related Art The use of bone stabilization/fixation devices to align or position bones is well established.","Furthermore, the use of spinal bone stabilization/fixation devices to align or position specific vertebrae or a region of the spine is well established.","Typically such devices for the spine utilize a spinal fixation element, comprised of a relatively rigid member such as a plate or a rod that is used as a coupler between adjacent vertebrae.","Such a spinal fixation element can effect a rigid positioning of adjacent vertebrae when attached to the pedicle portion of the vertebrae using pedicle bone anchorage screws.","Once the coupled vertebrae are spatially fixed in position, procedures can be performed, healing can proceed, or spinal fusion may take place.","Spinal fixation elements may be introduced to stabilize the various vertebrae of the spine.","Some devices for this purpose are designed to be attached directly to the spine, but the generally invasive nature of standard paraspinal approach used to implant these devices may pose drawbacks.","For example, muscle disruption and blood loss may result from standard paraspinal implantation approaches.","Conventional pedicle screw systems and even more recently designed pedicle screw systems also have several drawbacks.","Some of these pedicle screw systems are rather large and bulky, which may result in more tissue damage in and around the surgical site when the pedicle screw system is installed during surgery.","The prior art pedicle screw systems have a rod-receiving device that is pre-operatively coupled or attached to the pedicle screw.","In addition, some of the prior art pedicle screw systems include numerous components that must all be carefully assembled together.","Further, traditional pedicle screw systems are pre-operatively assembled, which makes these systems more difficult to install and maneuver in a spinal operation where MIS techniques are used.","BRIEF SUMMARY OF THE INVENTION A tulip assembly configured to be coupled to a screw head having a first diameter includes a housing, wherein the housing defines an inner diameter configured to engage the first diameter of the screw head.","The exemplary inner diameter of the housing being smaller than the first diameter of the screw head.","BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings illustrate various embodiments of the present system and method and are a part of the specification.","Together with the following description, the drawings demonstrate and explain the principles of the present system and method.","The illustrated embodiments are examples of the present system and method and do not limit the scope thereof.","FIG.","1 is an assembled perspective view of a press-on pedicle screw system, according to one exemplary embodiment.","FIG.","2 is a partial side unassembled view of a press-on pedicle screw system, according to one exemplary embodiment.","FIG.","3 is a side view of a pedicle screw, according to one exemplary embodiment.","FIG.","4 is a side partial cut-away view of a tulip and rod assembly of the press-on pedicle screw system of FIG.","1, according to one exemplary embodiment.","FIG.","5 is an exploded partial cut-away side view of the tulip assembly of FIG.","1, according to one exemplary embodiment.","FIG.","6 is an assembled partial cut-away side view of the pedicle screw system of FIG.","1, according to one exemplary embodiment.","FIGS.","7A and 7B are cross-sectional side-views of a press-on tulip bodies, according to various exemplary embodiments.","FIG.","8 is a partially exploded perspective view and of an alternative press-on pedicle screw system, according to one exemplary embodiment.","FIG.","9 is a cross-sectional partially exploded side view of the alternative press-on pedicle screw system of FIG.","8, according to one exemplary embodiment.","FIG.","10 is a flow chart illustrating a method for inserting a press-on tulip assembly on a pedicle screw, according to one exemplary embodiment.","Throughout the drawings, identical reference numbers designate similar but not necessarily identical elements.","DETAILED DESCRIPTION OF THE INVENTION The present specification describes a system and a method for securely coupling a tulip assembly relative to a pedicle screw via an interference fit.","Further, according to one exemplary embodiment, the present specification describes the structure of a tulip assembly configured to be placed on the head of a pedicle screw after placement of the pedicle screw in a patient's body and configured to receive and positionally secure a top loaded rod.","Further details of the present exemplary system and method will be provided below.","By way of example, pedicle screw systems may be fixed in the spine in a posterior lumbar fusion process via minimally invasive surgery (MIS) techniques.","The systems are inserted into the pedicles of the spine and then interconnected with rods to manipulate (e.g., correct the curvature, compress or expand, and/or structurally reinforce) at least portions of the spine.","Using the MIS approach to spinal fixation and/or correction surgery has been shown to decrease a patient's recovery time and reduce the risks of follow-up surgeries.","The ability to efficiently perform spinal fixation and/or correction surgeries using MIS techniques is enhanced by the use of pedicle screw systems provided in accordance with the present exemplary systems and methods, which systems and methods provide a number of advantages over conventional systems.","For example, a pedicle screw system in accordance with one embodiment of the present exemplary system and method provides the advantage that the pedicle screw may be inserted into the bone without being pre-operatively coupled with the rod-coupling assembly (hereinafter referred to as a tulip assembly).","This is advantageous because the surgeon often needs to do other inter-body work after inserting the pedicle screw, but before attaching the tulip assembly.","Such an advantageous pedicle screw system may be even more crucial when using MIS techniques because the inter-body spatial boundaries in which the surgeon must work may be quite limited.","In addition, pedicle screw systems in accordance with several embodiments of the present system and method advantageously reduce the overall size and height of the pedicle screw system when compared to traditional pedicle screw systems.","Reduced size and height of the pedicle screw system reduces tissue damage surrounding a surgical site and may also increase a patient's relative comfort.","The term “distraction,” when used herein and when used in a medical sense, generally relates to joint surfaces and suggests that the joint surfaces move perpendicular to one another.","However when “traction” and/or “distraction” is performed, for example on spinal sections, the spinal sections may move relative to one another through a combination of distraction and gliding, and/or other degrees of freedom.","Another advantageous feature of at least one embodiment of the present exemplary system and method is that an all-inclusive tulip assembly that can be coupled to the head portion of the pedicle screw intra-operatively is disclosed.","This advantageous tulip assembly may include the aspects or features that enable the tulip assembly to be locked onto the head portion of the pedicle screw.","The present exemplary tulip assembly may decrease the complexity of the pedicle screw system installation while simultaneously reducing the overall size of the pedicle screw system.","In the following description, for purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of the present system and method for providing a press-on screw assembly configured to be coupled to the head of a spinal fastener via a compression fit.","It will be apparent, however, to one skilled in the art that the present method may be practiced without these specific details.","Reference in the specification to “one embodiment” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment.","The appearance of the phrase “in one embodiment” in various places in the specification are not necessarily all referring to the same embodiment.","Exemplary Overall Structure While the present system and method may be practiced by any number of bone fixation systems, a first exemplary embodiment of the present system and method will be described herein, for ease of explanation only, in the context of a pedicle screw system.","Accordingly, the present system and method includes, according to one exemplary embodiment illustrated in FIG.","1, a pedicle screw system (100) including a pedicle screw (102), a rod member (104), and at least one coupling assemblies (106), herein after referred to as a tulip assembly (106).","According to one exemplary embodiment of the present system and method, the tulip assembly (106) is configured to receive and securely position the rod member (104).","Alternatively, as illustrated in FIG.","1, the at least one tulip assembly (106) may be securely and permanently coupled to the rod member (104) at a coupling site (107) via any number of coupling means, as will be described in detail below.","According to the present exemplary system and method, the at least one tulip assembly (106) is configured to be securely coupled to the pedicle screw (102) via an interference fit.","Operation of the tulip assembly (106) as well as its interaction with both the pedicle screw (102) and the rod (104) will be described in further detail below with reference to the Figures.","According to one exemplary embodiment, FIG.","1 generally shows a pedicle screw system (100) comprising a pedicle screw (102), a rod member (104), and a coupling assembly (106), hereinafter referred to as a tulip assembly (106).","As illustrated in FIG.","1, the pedicle screw system (100) is configured to securely couple the tulip assembly (106) to the pedicle screw (102), thereby locking or fixing the tulip assembly (106) in a relative angular position relative to the pedicle screw (102).","Additionally, as shown in FIG.","1, the present exemplary pedicle screw system (100) is devoid of separate pedicle screw coupling features and therefore is configured to couple the head of a pedicle screw while minimizing the outer diameter size of the tulip assembly (106).","FIG.","2 illustrates an unassembled exploded side view of the present pedicle screw system (100), according to one exemplary embodiment.","As illustrated in FIG.","2, the coupling assembly or tulip assembly (106) of the pedicle screw system (100) includes an engagement orifice (200) configured to engage the head portion (110) of the pedicle screw (102), as described in further detail below.","Detailed descriptions of each component of the present pedicle screw system (100), along with a number of alternative embodiments will be described in further detail below, with reference to FIGS.","2 through 9.FIG.","3 further illustrates the components of a pedicle screw (102) that may be used in connection with the present exemplary system and method, according to one exemplary embodiment.","As illustrated in FIG.","3, the pedicle screw (102) includes an elongated, threaded portion (108) and a head portion (110).","Although pedicle screws (102) are generally known in the art, the head portions (110) may be of varying configurations depending on what type of tulip assembly (160) is to be coupled to the pedicle screw (102).","The head portion (110) of the present exemplary pedicle screw (102) includes a driving feature (124) and a maximum diameter portion (126).","The driving feature (124) of the present exemplary pedicle screw (102) permits the screw to be inserted into a pedicle bone and/or other bone.","According to one exemplary embodiment, the pedicle bone is a part of a vertebra that connects the lamina with a vertebral body.","Additionally, according to the present exemplary embodiment, the driving feature (124) can be used to adjust the pedicle screw (102) prior to or after the tulip assembly (106) is coupled to the pedicle screw (102).","In the illustrated embodiment, the head portion (110) of the pedicle screw (102) is coupled to the threaded portion (108) and includes a generally spherical surface (127) with a truncated or flat top surface (128).","In one exemplary embodiment, the pedicle screw (102) is cannulated, which means a channel (130) (shown in dashed lines and extending axially through the pedicle screw (102)) extends through the entire length of the pedicle screw (102).","The channel (130) allows the pedicle screw (102) to be maneuvered over and receive a Kirschner wire, commonly referred to as a K-wire.","The K-wire is typically pre-positioned using imaging techniques, for example, fluoroscopy imaging, and then used to provide precise placement of the pedicle screw (102).","While the pedicle screw (102) illustrated in FIG.","3 includes a number of components, a number of variations may be made including, but in no way limited to, varying the type of driving feature (124), varying the shape and/or size of the head portion, varying materials, varying lengths, and the like.","Returning again to FIG.","1, the pedicle screw system includes a tulip assembly (106) configured to be locked to the head portion (110) of a pedicle screw (102) via an interference fit.","FIGS.","4, 5, and 6 illustrate the various components of the present exemplary tulip assembly (106), according to one exemplary embodiment.","FIG.","4 illustrates a partially cut-away view of a tulip assembly (106), according to one exemplary embodiment.","As illustrated in FIG.","4, the present exemplary tulip assembly (106) includes a generally cylindrical tulip body (450) defining an engagement orifice (200).","As shown in FIG.","4, the engagement orifice (200) defined by the generally cylindrical tulip body (450) includes a screw head contact surface (410) forming an inner wall portion of the engagement orifice (200).","According to one exemplary embodiment, when the present exemplary tulip assembly is coupled to the head portion (110) of a pedicle screw (102), the screw head contact surface (410) of the tulip assembly is sized to contact and securely couple the head portion of the pedicle screw via an interference fit.","Additionally, according to the exemplary embodiment illustrated in FIG.","4, an upper bore (400) is formed in the center of the tulip assembly (106) to provide access to and through the engagement orifice (200), thereby providing top access to a driving feature (124; FIG.","3) of a pedicle screw (102; FIG.","3) and/or a K-wire.","While on exemplary engagement orifice (200) including an upper bore (400) is illustrated in FIG.","4, any number of geometries may be used to define the engagement orifice (200) according to the teachings of the present exemplary system and method.","FIG.","5 further illustrates an exemplary configuration for practicing the present exemplary system and method.","As shown in FIG.","5, the present exemplary pedicle screw system (100) includes a rod member (104) permanently and securely coupled to a plurality of tulip assemblies (106).","By permanently coupling the rod member (104) to the outer housing of the tulip assemblies (106), rod binding mechanisms are unnecessary in the formation of the tulip assemblies (106).","Consequently, the outer diameter of the resulting pedicle screw system may be minimized, thereby reducing trauma and tissue damage to a patient.","According to one exemplary embodiment, the rod member (104) may be coupled to the outer surface of the tulip assemblies (106) by any number of methods including, but in no way limited to, welding, forming the system from a single piece of material, adhesives, mechanical fasteners, and the like.","As mentioned previously, each of the tulip assemblies (106) includes an engagement orifice (200) including a screw head contact surface (410).","According to one exemplary embodiment, the screw head contact surface (410) defines an internal diameter (500) of the tulip assembly (106).","Additionally, as illustrated in FIG.","5, the screw head (110) of the exemplary pedicle screw (102) has a maximum screw head diameter (550).","According to one exemplary embodiment of the present exemplary system and method, the internal diameter (500) defined by the screw head contact surface (410) is smaller than the maximum screw head diameter (550) of the screw head (110) of the exemplary pedicle screw (102), such that when the screw head of the exemplary pedicle screw (102) is pressed into the engagement orifice (200), the screw head and the screw head contact surface combine to create a press fit or an interference fit.","As used in the present specification, and in the appended claims, the term “interference fit” shall be interpreted broadly as including the joining of any two mating parts such that one or the other (or both) parts slightly deviate in size from their nominal dimension, thereby deforming each part slightly, each being compressed, the interface between two parts creating a union of extremely high friction.","The word interference refers to the fact that one part slightly interferes with the space that the other is occupying in its nominal dimension.","According to one exemplary embodiment, the allowance, or planned difference from nominal size of both the internal diameter (500) defined by the screw head contact surface (410) is smaller than the maximum screw head diameter (550) of the screw head (110) is sufficiently large that the force sufficient to overcome the resulting interference fit between the screw head contact surface (410) and the screw head (110) is larger than a force sufficient to pull the screw (102) out of a bone, or approximately 200 inch pounds.","FIG.","6 illustrates the engagement of a tulip assembly (106) on a pedicle screw (102), according to one exemplary embodiment.","As illustrated in FIG.","6, to engage the tulip assembly (106) to the screw head portion (110) of the pedicle screw (102), an instrument (not shown) can be coupled to the underside of the screw head (110) and to the top of the tulip assembly (106).","Once positioned, a load (F) can be applied to the top of the tulip assembly (106) to press the screw head (110) into the engagement orifice (200).","Similarly, disassembly can be achieved by pulling up on the tulip assembly (106) while driving an instrument through the upper bore (400) of the tulip assembly (106) to disengage the screw head (110) from the engagement orifice (200).","According to one exemplary embodiment, the desired interference fit sufficient to create a removal force of at least approximately 200 inch pounds may be dependent upon the materials used to form the screw head (110) and/or the screw head contact surface (410).","Particularly, according to one exemplary embodiment, the screw head (110) and/or the screw head contact surface (410) is formed of one of a titanium, a cobalt chrome, and/or a nitinol (nickel titanium) based material.","According to one exemplary embodiment, titanium, cobalt chrome, and/or nitinol, allow for a small amount of deformation without yielding.","Consequently, as illustrated above, the difference in the maximum screw head diameter (550) of the screw head (110) and the internal diameter (500) defined by the screw head contact surface (410) is sufficient to provide an interference fit between the screw head and the screw head receptacle, without yielding the material of either component.","Additionally, according to one exemplary embodiment, the interference fit is sufficiently strong to prevent the receptacle from being pulled off of the screw head, i.e., has a removal force of at least approximately 200 inch pounds.","According to one exemplary embodiment, the entire tulip assembly (106) may be formed of a known material such that the dimensions desired to create the interference fit can be readily calculated.","Alternatively, as illustrated in FIG.","7A, one or more inserts (710) may be formed in the engagement orifice (200) to provide a screw head contact surface (410) with known properties, while not requiring that the remaining tulip assembly exhibit those same qualities.","The placement of the one or more inserts (710) may be performed using any number of mechanical and/or chemical methods including, but in no way limited to, welding, using adhesives, material deposition methods, and the like.","While the interference fit provided above is described as occurring with only elastic deformation, the present system and method may be performed with slightly looser tolerances of the internal diameter (500) defined by the screw head contact surface (410) and the maximum screw head diameter (550) of the screw head (110) such that some plastic deformation occurs, so long as the removal force of the tulip assemblies (106) from the screw head (110) is sufficiently strong to prevent the receptacle from being pulled off of the screw head, i.e., has a removal force of at least approximately 200 inch pounds.","Furthermore, according to one exemplary embodiment, the surface defined by the screw head contact surface (410) has a constant diameter.","Consequently, a single interference fit is achieved when engaged with the screw head (110).","That is, according to one exemplary embodiment, the removal force will be substantially the same regardless of the level of engagement between the screw head contact surface (410) and the screw head (110).","Alternatively, according to one exemplary embodiment illustrated in FIG.","7B, the internal diameter (500) defined by the screw head contact surface (410) may vary, providing a potential for differing levels of engagement between the screw head contact surface (410) and the screw head (110).","Particularly, according to one exemplary embodiment, the tulip assembly (106) may have a first (750) and a second (755) internal diameter (500), both smaller than the maximum screw head diameter (550) of the screw head (110).","According to this exemplary embodiment, a first larger diameter (750) may be engaged or press fit to the head (110) of the pedicle screw to form a provisional lock, thereby establishing the engagement of the tulip assembly while providing some resisted movement.","Once a desired assembly and operation have been performed, the second smaller diameter (755) may be engaged with the maximum screw head diameter (550) of the screw head (110) to establish the final lock sufficient to maintain engagement.","While the above-mentioned exemplary embodiments are described as having the rod member (104) permanently coupled to the outer surface of the tulip assembly (106), thereby reducing the number of parts and the size of the pedicle screw system (100), any number of rod retention members may be formed in the upper portion of the tulip assembly to retain the rod member (104).","According to one exemplary embodiment illustrated in FIGS.","8 and 9, an exemplary pedicle screw system (800) includes a tulip member (806), having an upper portion and a lower portion.","According to the illustrated exemplary embodiment, the lower portion of the tulip member (806) includes an engagement orifice (200) to provide a screw head contact surface (410) as described above.","However, in contrast to the tulip members described previously, the upper portion of the exemplary tulip member (806) illustrated in FIG.","8 includes a threaded inner wall (810) configured to receive a set screw member (808).","Additionally, according to one exemplary embodiment, the exemplary tulip member (806) includes an orifice (900) passing through the walls of the exemplary tulip member (806).","According to one exemplary embodiment, the orifice is sufficiently sized to allow for the reception and translation of the rod member (104) there through.","As the rod member (104) is passed through the orifice (900), the set screw (808) may be advanced along the threaded inner wall (810) of the exemplary tulip member (806) until it engages the rod member (104) and imparts a retaining force thereon.","Exemplary Implementation and Operation FIG.","10 illustrates one exemplary method for utilizing the present exemplary press-on pedicle screw system, according to one exemplary embodiment.","As illustrated in FIG.","10, the exemplary method may begin by first inserting screws into a desired bone of a patient's spine (step 1010).","The placement and/or number of pedicle screw systems (100) to be used in a patient may be pre-operatively determined based on a pre-operative examination of the patient's spinal system using non-invasive imaging techniques known in the art, such as x-ray imaging, magnetic resonance imaging (MRI), and/or fluoroscopy imaging, for example.","The pedicle screws (102) may be maneuverable to achieve a desired placement, orientation, and/or angular position.","Once the desired pedicle screw (102) is properly placed (step 1010), a tulip member (806) may be inserted and guided to the previously placed screw (step 1020).","According to one exemplary embodiment, the placement of the tulip member (806) may be facilitated by the use of a Kirschner wire or non-invasive imaging methods including, but in no way limited to, x-ray imaging, magnetic resonance imaging (MRI), and/or fluoroscopy imaging, for example.","Once the tulip assembly (806) is at the desired position relative to the pedicle screw (102), the tulip assembly (806) can be fixed or locked onto the pedicle screw (102) by a downward force as described above.","According to one exemplary embodiment, the tulip assembly (806) is fixed onto the pedicle screw (102), at least provisionally (step 1040), before the rod member (104) is inserted into the tulip assembly (802) (step 1030).","In another embodiment, as illustrated in FIG.","10, the tulip assembly (806) is fixed onto the pedicle screw (102) contemporaneously as the rod is inserted into the tulip assembly (806), or even after the rod member (104) is inserted into the tulip assembly.","Once the tulip assembly (806) is provisionally retained on the screw (102), the rod (104) may be retained in the tulip assembly (806).","According to one exemplary embodiment, the rod member (104) may be captured by the tulip assembly (806) by advancing the set screw (808) along the threaded inner wall (810) of the exemplary tulip member (806) until the set screw engages the rod member (104) and imparts a retaining force thereon.","With the rod member (104) correctly positioned and any positional manipulation procedures completed, the tulip assembly (806) can be further advanced along the engagement orifice (200) to provide a final positional and angular lock of the tulip assembly relative to the screw (step 1060).","While the above-mentioned method is described and illustrated as a step-wise process, it will be understood that the illustrated order of performing the detailed steps is not necessary.","Rather, the steps of the exemplary method illustrated herein may be performed in any number of combinations to practice the present exemplary system and method.","Furthermore, a number of alternative embodiments may be formed using the present exemplary system and method.","For example, according to one exemplary embodiment, the spherical shaped screw head (110) detailed above may be replaced with a cylindrical member having an engagement orifice (200).","According to this exemplary embodiment, the rod connection member may be coupled to or include an integrally formed spherical member configured to be coupled to the engagement orifice (200) via an interference fit, as disclosed above.","Additionally, according to various exemplary embodiments, the spherical member of the present system may include a dual-lobed member having a different diameter for each lobe, thereby allowing for provisional and final lock using a corresponding member having a single internal diameter.","As described previously, assemblies detailed herein have a smaller size envelope (e.g., less bulky, lower profile, and/or more compact shape) and are easier to place onto the pedicle screw than traditional designs.","The smaller size and ease of installation may reduce trauma to the soft-tissue regions in the vicinity of the surgical site, which in turn generally allows for a quicker recovery by the patient.","Yet another possible advantage of the present exemplary pedicle screw systems over existing systems is that all of the parts needed to lock the tulip assembly to the pedicle screw are included within the tulip assembly.","Accordingly, once the tulip assembly is coupled to the pedicle screw, no additional member is needed to complete the assembly/installation of the pedicle screw system.","The preceding description has been presented only to illustrate and describe the present method and system.","It is not intended to be exhaustive or to limit the present system and method to any precise form disclosed.","Many modifications and variations are possible in light of the above teaching.","The foregoing embodiments were chosen and described in order to illustrate principles of the system and method as well as some practical applications.","The preceding description enables others skilled in the art to utilize the method and system in various embodiments and with various modifications as are suited to the particular use contemplated.","It is intended that the scope of the method and system be defined by the following claims."]],"string":"[\n [\n \"Press-On Pedicle Screw Assembly\",\n \"A tulip assembly configured to be coupled to a screw head having a first diameter includes a housing, wherein the housing defines an inner diameter configured to engage the first diameter of the screw head.\",\n \"The exemplary inner diameter of the housing being smaller than the first diameter of the screw head.\"\n ],\n [\n \"1.An implant assembly configured to be coupled to and extend between heads of two pedicle screws, each pedicle screw comprising a head having a head diameter and an elongate threaded portion coupled to and extending from the head, the implant assembly comprising: a first tulip assembly having a first cylindrical bore extending into the first tulip assembly, the first cylindrical bore having a first inner diameter defined by an inner wall of the first tulip assembly, the first inner diameter being smaller than the head diameter of the pedicle screws; a second tulip assembly having a first cylindrical bore extending into the second tulip assembly, the first cylindrical bore having a first inner diameter defined by an inner wall of the second tulip assembly, the first inner diameter being smaller than the head diameter of the pedicle screws; and a rod permanently connected to and extending between the first tulip assembly and the second tulip assembly.\",\n \"2.The implant assembly of claim 1, wherein the first tulip assembly, the second tulip assembly, and the rod are permanently coupled prior to coupling of the implant assembly to the two pedicle screws.\",\n \"3.The implant assembly of claim 1, wherein the first tulip assembly, the second tulip assembly, and the rod are unitarily formed from a single piece of material.\",\n \"4.The implant assembly of claim 1, wherein each of the first tulip assembly and the second tulip assembly further comprise a second cylindrical bore comprising: an axis of symmetry shared with an axis of symmetry of the first cylindrical bore of the respective tulip assembly; and an inner diameter smaller than the first inner diameter; wherein the second cylindrical bore extends into the housing from an internal end of the first cylindrical bore.\",\n \"5.The implant assembly of claim 1, wherein the first cylindrical bores of the first and second tulip assemblies permit head-first introduction of the head of one of the pedicle screws into the first cylindrical bore until a section having the head diameter is entirely within the first cylindrical bore, thereby creating a compression fit between the inner wall and the head of the pedicle screw within the first cylindrical bore due to the head diameter of the pedicle screw being larger than the inner diameter of the first cylindrical bore.\",\n \"6.The implant assembly of claim 5, wherein the compression fit between the inner wall and the head of the pedicle screw is capable of withstanding at least 200 pounds of removal force between the tulip assembly and the pedicle screw along an axis of the bore without relative movement of the screw head along the first cylindrical bore.\",\n \"7.The implant assembly of claim 5, wherein each tulip assembly is adapted to permit head-first introduction of the head of the pedicle screw into the first cylindrical bore to the point of creating the compression fit while at least a portion of the elongate threaded portion of the pedicle screw is embedded in bone.\",\n \"8.The implant assembly of claim 1, wherein the implant assembly further comprises two pedicle screws and wherein the head of each pedicle screw comprises a truncated spherical shape.\",\n \"9.The implant assembly of claim 1, wherein the implant assembly comprises a material selected from the group consisting of a titanium alloy, a cobalt chrome alloy, and a nickel titanium alloy.\",\n \"10.An implant assembly comprising: a pedicle screw comprising a head having a head diameter and an elongate threaded portion coupled to and extending from the head; and a tulip assembly comprising: a housing defining an engagement orifice and a bore extending into the housing from the engagement orifice, the engagement orifice and the bore having a fixed shape and an inner diameter that is smaller than the head diameter of the pedicle screw; wherein head-first introduction of the head of the pedicle screw through the engagement orifice and into the bore with the screw head in the bore creates a compression fit between the housing and the head of the pedicle screw due to the head diameter of the pedicle screw being larger than the inner diameter of the engagement orifice and the bore.\",\n \"11.The implant assembly of claim 10, wherein the compression fit between the housing and the head of the pedicle screw is capable of withstanding at least 200 pounds of removal force between the tulip assembly and the pedicle screw along an axis of the bore without relative movement of the screw head along the bore.\",\n \"12.The implant assembly of claim 10, wherein the bore is a first bore and the inner diameter is a first inner diameter, and wherein the tulip assembly further comprises a second bore comprising: an axis of symmetry parallel to an axis of symmetry of the first bore; and an inner diameter smaller than the first inner diameter; wherein the second bore extends into the housing from an internal end of the first bore.\",\n \"13.The implant assembly of claim 10, wherein the engagement orifice is circular and wherein the inner wall of the housing defines a cylindrical portion of the bore extending into the housing from the engagement orifice.\",\n \"14.The implant assembly of claim 10, wherein the head of the pedicle screw comprises a truncated spherical shape.\",\n \"15.The implant assembly of claim 10, wherein the assembly comprises two tulip assemblies, the tulip assemblies each being connected to a rod extending between the tulip assemblies.\",\n \"16.The implant assembly of claim 15, wherein the rod is permanently coupled to the two tulip assemblies prior to implantation of the implant assembly by introduction of a pedicle screw into the cylindrical bore of either tulip assembly.\",\n \"17.The implant assembly of claim 10, wherein said housing comprises a material selected from the group consisting of a titanium alloy, a cobalt chrome alloy, and a nickel titanium alloy.\",\n \"18.A method for affixing a press-on pedicle screw assembly to a spine, comprising: inserting a first pedicle screw having a head portion with a head diameter into a first desired bone of a patient's spine; inserting a second pedicle screw having a head portion with a head diameter into a second desired bone of a patient's spine; after the first and second pedicle screws are inserted into the bones of the patient's spine, guiding a tulip assembly having a housing defining an engagement orifice and a bore extending into the housing from the engagement orifice, the engagement orifice and the bore having a fixed shape and an inner diameter defined by an inner wall of the housing that is smaller than the head diameter of the pedicle screws, until the engagement orifice is proximate the head portion of the first pedicle screw; and applying a force between the first pedicle screw and the tulip assembly whereby the head portion of the pedicle screw is drawn into the bore of the tulip assembly, thereby creating a compression fit between the inner wall of the housing and the head of the pedicle screw due to the head diameter of the pedicle screw being larger than the inner diameter of the engagement orifice and the bore.\",\n \"19.The method as recited in claim 18, wherein the tulip assembly is a first tulip assembly of an implant assembly comprising two tulip assemblies, the method further comprising: positioning a second tulip assembly with its engagement orifice proximate the head portion of the second pedicle screw; and applying a force between the second pedicle screw and the second tulip assembly whereby the head portion of the second pedicle screw is drawn into the bore of the second tulip assembly, thereby creating a compression fit between the inner wall of the housing and the head of the second pedicle screw due to the head diameter of the second pedicle screw being larger than the inner diameter of the engagement orifice and the bore.\",\n \"20.The method as recited in claim 19, further comprising connecting the two tulip assemblies together via a rod before engaging either tulip assembly to either pedicle screw via the compression fit.\"\n ],\n [\n \" 2.Background and Related Art 2 .\",\n \"Background and Related Art The use of bone stabilization/fixation devices to align or position bones is well established.\",\n \"Furthermore, the use of spinal bone stabilization/fixation devices to align or position specific vertebrae or a region of the spine is well established.\",\n \"Typically such devices for the spine utilize a spinal fixation element, comprised of a relatively rigid member such as a plate or a rod that is used as a coupler between adjacent vertebrae.\",\n \"Such a spinal fixation element can effect a rigid positioning of adjacent vertebrae when attached to the pedicle portion of the vertebrae using pedicle bone anchorage screws.\",\n \"Once the coupled vertebrae are spatially fixed in position, procedures can be performed, healing can proceed, or spinal fusion may take place.\",\n \"Spinal fixation elements may be introduced to stabilize the various vertebrae of the spine.\",\n \"Some devices for this purpose are designed to be attached directly to the spine, but the generally invasive nature of standard paraspinal approach used to implant these devices may pose drawbacks.\",\n \"For example, muscle disruption and blood loss may result from standard paraspinal implantation approaches.\",\n \"Conventional pedicle screw systems and even more recently designed pedicle screw systems also have several drawbacks.\",\n \"Some of these pedicle screw systems are rather large and bulky, which may result in more tissue damage in and around the surgical site when the pedicle screw system is installed during surgery.\",\n \"The prior art pedicle screw systems have a rod-receiving device that is pre-operatively coupled or attached to the pedicle screw.\",\n \"In addition, some of the prior art pedicle screw systems include numerous components that must all be carefully assembled together.\",\n \"Further, traditional pedicle screw systems are pre-operatively assembled, which makes these systems more difficult to install and maneuver in a spinal operation where MIS techniques are used.\"\n ],\n [\n \" BRIEF SUMMARY OF THE INVENTION A tulip assembly configured to be coupled to a screw head having a first diameter includes a housing, wherein the housing defines an inner diameter configured to engage the first diameter of the screw head.\",\n \"The exemplary inner diameter of the housing being smaller than the first diameter of the screw head.\"\n ],\n [\n \"CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of U.S. patent application Ser.\",\n \"No.\",\n \"11/952,709 filed Dec. 7, 2007 which claims the benefit under 35 U.S.C.§ 119(e) of U.S.\",\n \"Provisional Patent Application No: 60/873,698, filed Dec. 7, 2006, titled “Press on Screw Tulip,” which applications are incorporated herein by reference in their entirety.\",\n \"TECHNICAL FIELD 1.Field of the Invention The present exemplary system and method relates to medical devices.\",\n \"More particularly, the present exemplary system and method relates to percutaneous orthopedic rod placement devices.\",\n \"2.Background and Related Art The use of bone stabilization/fixation devices to align or position bones is well established.\",\n \"Furthermore, the use of spinal bone stabilization/fixation devices to align or position specific vertebrae or a region of the spine is well established.\",\n \"Typically such devices for the spine utilize a spinal fixation element, comprised of a relatively rigid member such as a plate or a rod that is used as a coupler between adjacent vertebrae.\",\n \"Such a spinal fixation element can effect a rigid positioning of adjacent vertebrae when attached to the pedicle portion of the vertebrae using pedicle bone anchorage screws.\",\n \"Once the coupled vertebrae are spatially fixed in position, procedures can be performed, healing can proceed, or spinal fusion may take place.\",\n \"Spinal fixation elements may be introduced to stabilize the various vertebrae of the spine.\",\n \"Some devices for this purpose are designed to be attached directly to the spine, but the generally invasive nature of standard paraspinal approach used to implant these devices may pose drawbacks.\",\n \"For example, muscle disruption and blood loss may result from standard paraspinal implantation approaches.\",\n \"Conventional pedicle screw systems and even more recently designed pedicle screw systems also have several drawbacks.\",\n \"Some of these pedicle screw systems are rather large and bulky, which may result in more tissue damage in and around the surgical site when the pedicle screw system is installed during surgery.\",\n \"The prior art pedicle screw systems have a rod-receiving device that is pre-operatively coupled or attached to the pedicle screw.\",\n \"In addition, some of the prior art pedicle screw systems include numerous components that must all be carefully assembled together.\",\n \"Further, traditional pedicle screw systems are pre-operatively assembled, which makes these systems more difficult to install and maneuver in a spinal operation where MIS techniques are used.\",\n \"BRIEF SUMMARY OF THE INVENTION A tulip assembly configured to be coupled to a screw head having a first diameter includes a housing, wherein the housing defines an inner diameter configured to engage the first diameter of the screw head.\",\n \"The exemplary inner diameter of the housing being smaller than the first diameter of the screw head.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings illustrate various embodiments of the present system and method and are a part of the specification.\",\n \"Together with the following description, the drawings demonstrate and explain the principles of the present system and method.\",\n \"The illustrated embodiments are examples of the present system and method and do not limit the scope thereof.\",\n \"FIG.\",\n \"1 is an assembled perspective view of a press-on pedicle screw system, according to one exemplary embodiment.\",\n \"FIG.\",\n \"2 is a partial side unassembled view of a press-on pedicle screw system, according to one exemplary embodiment.\",\n \"FIG.\",\n \"3 is a side view of a pedicle screw, according to one exemplary embodiment.\",\n \"FIG.\",\n \"4 is a side partial cut-away view of a tulip and rod assembly of the press-on pedicle screw system of FIG.\",\n \"1, according to one exemplary embodiment.\",\n \"FIG.\",\n \"5 is an exploded partial cut-away side view of the tulip assembly of FIG.\",\n \"1, according to one exemplary embodiment.\",\n \"FIG.\",\n \"6 is an assembled partial cut-away side view of the pedicle screw system of FIG.\",\n \"1, according to one exemplary embodiment.\",\n \"FIGS.\",\n \"7A and 7B are cross-sectional side-views of a press-on tulip bodies, according to various exemplary embodiments.\",\n \"FIG.\",\n \"8 is a partially exploded perspective view and of an alternative press-on pedicle screw system, according to one exemplary embodiment.\",\n \"FIG.\",\n \"9 is a cross-sectional partially exploded side view of the alternative press-on pedicle screw system of FIG.\",\n \"8, according to one exemplary embodiment.\",\n \"FIG.\",\n \"10 is a flow chart illustrating a method for inserting a press-on tulip assembly on a pedicle screw, according to one exemplary embodiment.\",\n \"Throughout the drawings, identical reference numbers designate similar but not necessarily identical elements.\",\n \"DETAILED DESCRIPTION OF THE INVENTION The present specification describes a system and a method for securely coupling a tulip assembly relative to a pedicle screw via an interference fit.\",\n \"Further, according to one exemplary embodiment, the present specification describes the structure of a tulip assembly configured to be placed on the head of a pedicle screw after placement of the pedicle screw in a patient's body and configured to receive and positionally secure a top loaded rod.\",\n \"Further details of the present exemplary system and method will be provided below.\",\n \"By way of example, pedicle screw systems may be fixed in the spine in a posterior lumbar fusion process via minimally invasive surgery (MIS) techniques.\",\n \"The systems are inserted into the pedicles of the spine and then interconnected with rods to manipulate (e.g., correct the curvature, compress or expand, and/or structurally reinforce) at least portions of the spine.\",\n \"Using the MIS approach to spinal fixation and/or correction surgery has been shown to decrease a patient's recovery time and reduce the risks of follow-up surgeries.\",\n \"The ability to efficiently perform spinal fixation and/or correction surgeries using MIS techniques is enhanced by the use of pedicle screw systems provided in accordance with the present exemplary systems and methods, which systems and methods provide a number of advantages over conventional systems.\",\n \"For example, a pedicle screw system in accordance with one embodiment of the present exemplary system and method provides the advantage that the pedicle screw may be inserted into the bone without being pre-operatively coupled with the rod-coupling assembly (hereinafter referred to as a tulip assembly).\",\n \"This is advantageous because the surgeon often needs to do other inter-body work after inserting the pedicle screw, but before attaching the tulip assembly.\",\n \"Such an advantageous pedicle screw system may be even more crucial when using MIS techniques because the inter-body spatial boundaries in which the surgeon must work may be quite limited.\",\n \"In addition, pedicle screw systems in accordance with several embodiments of the present system and method advantageously reduce the overall size and height of the pedicle screw system when compared to traditional pedicle screw systems.\",\n \"Reduced size and height of the pedicle screw system reduces tissue damage surrounding a surgical site and may also increase a patient's relative comfort.\",\n \"The term “distraction,” when used herein and when used in a medical sense, generally relates to joint surfaces and suggests that the joint surfaces move perpendicular to one another.\",\n \"However when “traction” and/or “distraction” is performed, for example on spinal sections, the spinal sections may move relative to one another through a combination of distraction and gliding, and/or other degrees of freedom.\",\n \"Another advantageous feature of at least one embodiment of the present exemplary system and method is that an all-inclusive tulip assembly that can be coupled to the head portion of the pedicle screw intra-operatively is disclosed.\",\n \"This advantageous tulip assembly may include the aspects or features that enable the tulip assembly to be locked onto the head portion of the pedicle screw.\",\n \"The present exemplary tulip assembly may decrease the complexity of the pedicle screw system installation while simultaneously reducing the overall size of the pedicle screw system.\",\n \"In the following description, for purposes of explanation, numerous specific details are set forth in order to provide a thorough understanding of the present system and method for providing a press-on screw assembly configured to be coupled to the head of a spinal fastener via a compression fit.\",\n \"It will be apparent, however, to one skilled in the art that the present method may be practiced without these specific details.\",\n \"Reference in the specification to “one embodiment” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment.\",\n \"The appearance of the phrase “in one embodiment” in various places in the specification are not necessarily all referring to the same embodiment.\",\n \"Exemplary Overall Structure While the present system and method may be practiced by any number of bone fixation systems, a first exemplary embodiment of the present system and method will be described herein, for ease of explanation only, in the context of a pedicle screw system.\",\n \"Accordingly, the present system and method includes, according to one exemplary embodiment illustrated in FIG.\",\n \"1, a pedicle screw system (100) including a pedicle screw (102), a rod member (104), and at least one coupling assemblies (106), herein after referred to as a tulip assembly (106).\",\n \"According to one exemplary embodiment of the present system and method, the tulip assembly (106) is configured to receive and securely position the rod member (104).\",\n \"Alternatively, as illustrated in FIG.\",\n \"1, the at least one tulip assembly (106) may be securely and permanently coupled to the rod member (104) at a coupling site (107) via any number of coupling means, as will be described in detail below.\",\n \"According to the present exemplary system and method, the at least one tulip assembly (106) is configured to be securely coupled to the pedicle screw (102) via an interference fit.\",\n \"Operation of the tulip assembly (106) as well as its interaction with both the pedicle screw (102) and the rod (104) will be described in further detail below with reference to the Figures.\",\n \"According to one exemplary embodiment, FIG.\",\n \"1 generally shows a pedicle screw system (100) comprising a pedicle screw (102), a rod member (104), and a coupling assembly (106), hereinafter referred to as a tulip assembly (106).\",\n \"As illustrated in FIG.\",\n \"1, the pedicle screw system (100) is configured to securely couple the tulip assembly (106) to the pedicle screw (102), thereby locking or fixing the tulip assembly (106) in a relative angular position relative to the pedicle screw (102).\",\n \"Additionally, as shown in FIG.\",\n \"1, the present exemplary pedicle screw system (100) is devoid of separate pedicle screw coupling features and therefore is configured to couple the head of a pedicle screw while minimizing the outer diameter size of the tulip assembly (106).\",\n \"FIG.\",\n \"2 illustrates an unassembled exploded side view of the present pedicle screw system (100), according to one exemplary embodiment.\",\n \"As illustrated in FIG.\",\n \"2, the coupling assembly or tulip assembly (106) of the pedicle screw system (100) includes an engagement orifice (200) configured to engage the head portion (110) of the pedicle screw (102), as described in further detail below.\",\n \"Detailed descriptions of each component of the present pedicle screw system (100), along with a number of alternative embodiments will be described in further detail below, with reference to FIGS.\",\n \"2 through 9.FIG.\",\n \"3 further illustrates the components of a pedicle screw (102) that may be used in connection with the present exemplary system and method, according to one exemplary embodiment.\",\n \"As illustrated in FIG.\",\n \"3, the pedicle screw (102) includes an elongated, threaded portion (108) and a head portion (110).\",\n \"Although pedicle screws (102) are generally known in the art, the head portions (110) may be of varying configurations depending on what type of tulip assembly (160) is to be coupled to the pedicle screw (102).\",\n \"The head portion (110) of the present exemplary pedicle screw (102) includes a driving feature (124) and a maximum diameter portion (126).\",\n \"The driving feature (124) of the present exemplary pedicle screw (102) permits the screw to be inserted into a pedicle bone and/or other bone.\",\n \"According to one exemplary embodiment, the pedicle bone is a part of a vertebra that connects the lamina with a vertebral body.\",\n \"Additionally, according to the present exemplary embodiment, the driving feature (124) can be used to adjust the pedicle screw (102) prior to or after the tulip assembly (106) is coupled to the pedicle screw (102).\",\n \"In the illustrated embodiment, the head portion (110) of the pedicle screw (102) is coupled to the threaded portion (108) and includes a generally spherical surface (127) with a truncated or flat top surface (128).\",\n \"In one exemplary embodiment, the pedicle screw (102) is cannulated, which means a channel (130) (shown in dashed lines and extending axially through the pedicle screw (102)) extends through the entire length of the pedicle screw (102).\",\n \"The channel (130) allows the pedicle screw (102) to be maneuvered over and receive a Kirschner wire, commonly referred to as a K-wire.\",\n \"The K-wire is typically pre-positioned using imaging techniques, for example, fluoroscopy imaging, and then used to provide precise placement of the pedicle screw (102).\",\n \"While the pedicle screw (102) illustrated in FIG.\",\n \"3 includes a number of components, a number of variations may be made including, but in no way limited to, varying the type of driving feature (124), varying the shape and/or size of the head portion, varying materials, varying lengths, and the like.\",\n \"Returning again to FIG.\",\n \"1, the pedicle screw system includes a tulip assembly (106) configured to be locked to the head portion (110) of a pedicle screw (102) via an interference fit.\",\n \"FIGS.\",\n \"4, 5, and 6 illustrate the various components of the present exemplary tulip assembly (106), according to one exemplary embodiment.\",\n \"FIG.\",\n \"4 illustrates a partially cut-away view of a tulip assembly (106), according to one exemplary embodiment.\",\n \"As illustrated in FIG.\",\n \"4, the present exemplary tulip assembly (106) includes a generally cylindrical tulip body (450) defining an engagement orifice (200).\",\n \"As shown in FIG.\",\n \"4, the engagement orifice (200) defined by the generally cylindrical tulip body (450) includes a screw head contact surface (410) forming an inner wall portion of the engagement orifice (200).\",\n \"According to one exemplary embodiment, when the present exemplary tulip assembly is coupled to the head portion (110) of a pedicle screw (102), the screw head contact surface (410) of the tulip assembly is sized to contact and securely couple the head portion of the pedicle screw via an interference fit.\",\n \"Additionally, according to the exemplary embodiment illustrated in FIG.\",\n \"4, an upper bore (400) is formed in the center of the tulip assembly (106) to provide access to and through the engagement orifice (200), thereby providing top access to a driving feature (124; FIG.\",\n \"3) of a pedicle screw (102; FIG.\",\n \"3) and/or a K-wire.\",\n \"While on exemplary engagement orifice (200) including an upper bore (400) is illustrated in FIG.\",\n \"4, any number of geometries may be used to define the engagement orifice (200) according to the teachings of the present exemplary system and method.\",\n \"FIG.\",\n \"5 further illustrates an exemplary configuration for practicing the present exemplary system and method.\",\n \"As shown in FIG.\",\n \"5, the present exemplary pedicle screw system (100) includes a rod member (104) permanently and securely coupled to a plurality of tulip assemblies (106).\",\n \"By permanently coupling the rod member (104) to the outer housing of the tulip assemblies (106), rod binding mechanisms are unnecessary in the formation of the tulip assemblies (106).\",\n \"Consequently, the outer diameter of the resulting pedicle screw system may be minimized, thereby reducing trauma and tissue damage to a patient.\",\n \"According to one exemplary embodiment, the rod member (104) may be coupled to the outer surface of the tulip assemblies (106) by any number of methods including, but in no way limited to, welding, forming the system from a single piece of material, adhesives, mechanical fasteners, and the like.\",\n \"As mentioned previously, each of the tulip assemblies (106) includes an engagement orifice (200) including a screw head contact surface (410).\",\n \"According to one exemplary embodiment, the screw head contact surface (410) defines an internal diameter (500) of the tulip assembly (106).\",\n \"Additionally, as illustrated in FIG.\",\n \"5, the screw head (110) of the exemplary pedicle screw (102) has a maximum screw head diameter (550).\",\n \"According to one exemplary embodiment of the present exemplary system and method, the internal diameter (500) defined by the screw head contact surface (410) is smaller than the maximum screw head diameter (550) of the screw head (110) of the exemplary pedicle screw (102), such that when the screw head of the exemplary pedicle screw (102) is pressed into the engagement orifice (200), the screw head and the screw head contact surface combine to create a press fit or an interference fit.\",\n \"As used in the present specification, and in the appended claims, the term “interference fit” shall be interpreted broadly as including the joining of any two mating parts such that one or the other (or both) parts slightly deviate in size from their nominal dimension, thereby deforming each part slightly, each being compressed, the interface between two parts creating a union of extremely high friction.\",\n \"The word interference refers to the fact that one part slightly interferes with the space that the other is occupying in its nominal dimension.\",\n \"According to one exemplary embodiment, the allowance, or planned difference from nominal size of both the internal diameter (500) defined by the screw head contact surface (410) is smaller than the maximum screw head diameter (550) of the screw head (110) is sufficiently large that the force sufficient to overcome the resulting interference fit between the screw head contact surface (410) and the screw head (110) is larger than a force sufficient to pull the screw (102) out of a bone, or approximately 200 inch pounds.\",\n \"FIG.\",\n \"6 illustrates the engagement of a tulip assembly (106) on a pedicle screw (102), according to one exemplary embodiment.\",\n \"As illustrated in FIG.\",\n \"6, to engage the tulip assembly (106) to the screw head portion (110) of the pedicle screw (102), an instrument (not shown) can be coupled to the underside of the screw head (110) and to the top of the tulip assembly (106).\",\n \"Once positioned, a load (F) can be applied to the top of the tulip assembly (106) to press the screw head (110) into the engagement orifice (200).\",\n \"Similarly, disassembly can be achieved by pulling up on the tulip assembly (106) while driving an instrument through the upper bore (400) of the tulip assembly (106) to disengage the screw head (110) from the engagement orifice (200).\",\n \"According to one exemplary embodiment, the desired interference fit sufficient to create a removal force of at least approximately 200 inch pounds may be dependent upon the materials used to form the screw head (110) and/or the screw head contact surface (410).\",\n \"Particularly, according to one exemplary embodiment, the screw head (110) and/or the screw head contact surface (410) is formed of one of a titanium, a cobalt chrome, and/or a nitinol (nickel titanium) based material.\",\n \"According to one exemplary embodiment, titanium, cobalt chrome, and/or nitinol, allow for a small amount of deformation without yielding.\",\n \"Consequently, as illustrated above, the difference in the maximum screw head diameter (550) of the screw head (110) and the internal diameter (500) defined by the screw head contact surface (410) is sufficient to provide an interference fit between the screw head and the screw head receptacle, without yielding the material of either component.\",\n \"Additionally, according to one exemplary embodiment, the interference fit is sufficiently strong to prevent the receptacle from being pulled off of the screw head, i.e., has a removal force of at least approximately 200 inch pounds.\",\n \"According to one exemplary embodiment, the entire tulip assembly (106) may be formed of a known material such that the dimensions desired to create the interference fit can be readily calculated.\",\n \"Alternatively, as illustrated in FIG.\",\n \"7A, one or more inserts (710) may be formed in the engagement orifice (200) to provide a screw head contact surface (410) with known properties, while not requiring that the remaining tulip assembly exhibit those same qualities.\",\n \"The placement of the one or more inserts (710) may be performed using any number of mechanical and/or chemical methods including, but in no way limited to, welding, using adhesives, material deposition methods, and the like.\",\n \"While the interference fit provided above is described as occurring with only elastic deformation, the present system and method may be performed with slightly looser tolerances of the internal diameter (500) defined by the screw head contact surface (410) and the maximum screw head diameter (550) of the screw head (110) such that some plastic deformation occurs, so long as the removal force of the tulip assemblies (106) from the screw head (110) is sufficiently strong to prevent the receptacle from being pulled off of the screw head, i.e., has a removal force of at least approximately 200 inch pounds.\",\n \"Furthermore, according to one exemplary embodiment, the surface defined by the screw head contact surface (410) has a constant diameter.\",\n \"Consequently, a single interference fit is achieved when engaged with the screw head (110).\",\n \"That is, according to one exemplary embodiment, the removal force will be substantially the same regardless of the level of engagement between the screw head contact surface (410) and the screw head (110).\",\n \"Alternatively, according to one exemplary embodiment illustrated in FIG.\",\n \"7B, the internal diameter (500) defined by the screw head contact surface (410) may vary, providing a potential for differing levels of engagement between the screw head contact surface (410) and the screw head (110).\",\n \"Particularly, according to one exemplary embodiment, the tulip assembly (106) may have a first (750) and a second (755) internal diameter (500), both smaller than the maximum screw head diameter (550) of the screw head (110).\",\n \"According to this exemplary embodiment, a first larger diameter (750) may be engaged or press fit to the head (110) of the pedicle screw to form a provisional lock, thereby establishing the engagement of the tulip assembly while providing some resisted movement.\",\n \"Once a desired assembly and operation have been performed, the second smaller diameter (755) may be engaged with the maximum screw head diameter (550) of the screw head (110) to establish the final lock sufficient to maintain engagement.\",\n \"While the above-mentioned exemplary embodiments are described as having the rod member (104) permanently coupled to the outer surface of the tulip assembly (106), thereby reducing the number of parts and the size of the pedicle screw system (100), any number of rod retention members may be formed in the upper portion of the tulip assembly to retain the rod member (104).\",\n \"According to one exemplary embodiment illustrated in FIGS.\",\n \"8 and 9, an exemplary pedicle screw system (800) includes a tulip member (806), having an upper portion and a lower portion.\",\n \"According to the illustrated exemplary embodiment, the lower portion of the tulip member (806) includes an engagement orifice (200) to provide a screw head contact surface (410) as described above.\",\n \"However, in contrast to the tulip members described previously, the upper portion of the exemplary tulip member (806) illustrated in FIG.\",\n \"8 includes a threaded inner wall (810) configured to receive a set screw member (808).\",\n \"Additionally, according to one exemplary embodiment, the exemplary tulip member (806) includes an orifice (900) passing through the walls of the exemplary tulip member (806).\",\n \"According to one exemplary embodiment, the orifice is sufficiently sized to allow for the reception and translation of the rod member (104) there through.\",\n \"As the rod member (104) is passed through the orifice (900), the set screw (808) may be advanced along the threaded inner wall (810) of the exemplary tulip member (806) until it engages the rod member (104) and imparts a retaining force thereon.\",\n \"Exemplary Implementation and Operation FIG.\",\n \"10 illustrates one exemplary method for utilizing the present exemplary press-on pedicle screw system, according to one exemplary embodiment.\",\n \"As illustrated in FIG.\",\n \"10, the exemplary method may begin by first inserting screws into a desired bone of a patient's spine (step 1010).\",\n \"The placement and/or number of pedicle screw systems (100) to be used in a patient may be pre-operatively determined based on a pre-operative examination of the patient's spinal system using non-invasive imaging techniques known in the art, such as x-ray imaging, magnetic resonance imaging (MRI), and/or fluoroscopy imaging, for example.\",\n \"The pedicle screws (102) may be maneuverable to achieve a desired placement, orientation, and/or angular position.\",\n \"Once the desired pedicle screw (102) is properly placed (step 1010), a tulip member (806) may be inserted and guided to the previously placed screw (step 1020).\",\n \"According to one exemplary embodiment, the placement of the tulip member (806) may be facilitated by the use of a Kirschner wire or non-invasive imaging methods including, but in no way limited to, x-ray imaging, magnetic resonance imaging (MRI), and/or fluoroscopy imaging, for example.\",\n \"Once the tulip assembly (806) is at the desired position relative to the pedicle screw (102), the tulip assembly (806) can be fixed or locked onto the pedicle screw (102) by a downward force as described above.\",\n \"According to one exemplary embodiment, the tulip assembly (806) is fixed onto the pedicle screw (102), at least provisionally (step 1040), before the rod member (104) is inserted into the tulip assembly (802) (step 1030).\",\n \"In another embodiment, as illustrated in FIG.\",\n \"10, the tulip assembly (806) is fixed onto the pedicle screw (102) contemporaneously as the rod is inserted into the tulip assembly (806), or even after the rod member (104) is inserted into the tulip assembly.\",\n \"Once the tulip assembly (806) is provisionally retained on the screw (102), the rod (104) may be retained in the tulip assembly (806).\",\n \"According to one exemplary embodiment, the rod member (104) may be captured by the tulip assembly (806) by advancing the set screw (808) along the threaded inner wall (810) of the exemplary tulip member (806) until the set screw engages the rod member (104) and imparts a retaining force thereon.\",\n \"With the rod member (104) correctly positioned and any positional manipulation procedures completed, the tulip assembly (806) can be further advanced along the engagement orifice (200) to provide a final positional and angular lock of the tulip assembly relative to the screw (step 1060).\",\n \"While the above-mentioned method is described and illustrated as a step-wise process, it will be understood that the illustrated order of performing the detailed steps is not necessary.\",\n \"Rather, the steps of the exemplary method illustrated herein may be performed in any number of combinations to practice the present exemplary system and method.\",\n \"Furthermore, a number of alternative embodiments may be formed using the present exemplary system and method.\",\n \"For example, according to one exemplary embodiment, the spherical shaped screw head (110) detailed above may be replaced with a cylindrical member having an engagement orifice (200).\",\n \"According to this exemplary embodiment, the rod connection member may be coupled to or include an integrally formed spherical member configured to be coupled to the engagement orifice (200) via an interference fit, as disclosed above.\",\n \"Additionally, according to various exemplary embodiments, the spherical member of the present system may include a dual-lobed member having a different diameter for each lobe, thereby allowing for provisional and final lock using a corresponding member having a single internal diameter.\",\n \"As described previously, assemblies detailed herein have a smaller size envelope (e.g., less bulky, lower profile, and/or more compact shape) and are easier to place onto the pedicle screw than traditional designs.\",\n \"The smaller size and ease of installation may reduce trauma to the soft-tissue regions in the vicinity of the surgical site, which in turn generally allows for a quicker recovery by the patient.\",\n \"Yet another possible advantage of the present exemplary pedicle screw systems over existing systems is that all of the parts needed to lock the tulip assembly to the pedicle screw are included within the tulip assembly.\",\n \"Accordingly, once the tulip assembly is coupled to the pedicle screw, no additional member is needed to complete the assembly/installation of the pedicle screw system.\",\n \"The preceding description has been presented only to illustrate and describe the present method and system.\",\n \"It is not intended to be exhaustive or to limit the present system and method to any precise form disclosed.\",\n \"Many modifications and variations are possible in light of the above teaching.\",\n \"The foregoing embodiments were chosen and described in order to illustrate principles of the system and method as well as some practical applications.\",\n \"The preceding description enables others skilled in the art to utilize the method and system in various embodiments and with various modifications as are suited to the particular use contemplated.\",\n \"It is intended that the scope of the method and system be defined by the following claims.\"\n ]\n]"},"source":{"kind":"string","value":"Patent_15871973"}}},{"rowIdx":4493969,"cells":{"text":{"kind":"list like","value":[["Large mirror inside an autonomous vehicle","A large mirroring element is located in front of an occupant who sits in a front seat of an autonomous on-road vehicle.","The large mirroring element provides the effect of reflecting light arriving from the occupant's direction.","Optionally, a camera takes video of the outside environment in front of the occupant, sends the video to a computer that generates a representation of the outside environment in front of the occupant at eye level, and a display located in front of the occupant presents the representation to the occupant."],["1.An autonomous on-road vehicle providing the effect of a large front mirror, comprising: a compartment; and a mirroring element located in front of an occupant who sits in a front seat of the compartment; wherein the mirroring element captures at least 10×10 degrees of the occupant's forward field of view from the horizon to at least 10° below the horizon during normal driving, and provides an effect of reflecting more than 25% of the light arriving from the occupant's direction.","2.The autonomous on-road vehicle of claim 1, wherein height and width of the mirroring element exceeds 50×40 cm, and the mirroring element captures above 30×30 degrees of the occupant's field of view, from the horizon to 30° below the horizon.","3.The autonomous on-road vehicle of claim 1, wherein height and width of the mirroring element exceeds 25×25 cm, and the mirroring element captures more than 25% of the area where a conventional windshield of a normal non-autonomous road vehicle in year 2016 is expected to be located.","4.The autonomous on-road vehicle of claim 1, wherein the mirroring element increases the volume of the vehicle compartment as perceived by the occupant due to the reflection effect, and the mirroring element provides an effect of reflecting more than at least one of 50%, 80%, and 90% of the light arriving from the occupant's direction.","5.The autonomous on-road vehicle of claim 1, wherein the mirroring element comprises an optical mirror, and most of the effect of reflecting is generated by the optical mirror.","6.The autonomous on-road vehicle of claim 1, wherein the mirroring element comprises a Fresnel type optical reflector comprising reflecting prisms; wherein the Fresnel type optical reflector is not flat, but the reflecting prisms are arranged in angles that reflect the light from the occupant such as to imitate an essentially flat mirror.","7.The autonomous on-road vehicle of claim 1, wherein the effect of reflecting is achieved by a digital mirror; wherein the digital mirror comprises: multiple cameras embedded within the digital mirror and configured to take images of the occupant, and multiple light emitting pixels configured to emit light rays that generate the effect of reflecting.","8.The autonomous on-road vehicle of claim 1, wherein the mirroring element comprises an electronic display, and further comprising at least one camera configured to take video of the occupant, and a computer configured to generate, based on the video of the occupant, video to be displayed by the electronic display in order to generate the effect of reflecting.","9.The autonomous on-road vehicle of claim 8, wherein the at least one camera comprises first and second cameras, located to the right and left of the occupant, respectively.","10.The autonomous on-road vehicle of claim 8, wherein the at least one camera comprises first and second cameras, located above the level of the occupant's nose and below the level of the occupant's collarbone, respectively, and less than 80 cm away from the occupant.","11.The autonomous on-road vehicle of claim 8, further comprising a camera configured to take video of the outside environment in front of the occupant, and the computer is further configured to generate, based on the video, a representation of the outside environment in front of the occupant, at eye level, to be displayed by the mirroring element to the occupant.","12.The autonomous on-road vehicle of claim 11, wherein the mirroring element is further configured to operate in a second state in which it: (i) provides the effect of reflecting less than 20% of the light arriving from the occupant's direction, and (ii) presents to the occupant the representation of the outside environment; whereby presenting the representation of the outside environment imitates a windshield to the outside environment.","13.The autonomous on-road vehicle of claim 11, further comprising a user interface configured to enable the occupant to switch between seeing the effect of reflecting and seeing the representation of the outside environment.","14.The autonomous on-road vehicle of claim 11, wherein the electronic display is comprised in a head-mounted display (HMD).","15.The autonomous on-road vehicle of claim 11, wherein the electronic display is mechanically coupled to the compartment, and/or the mirroring element comprises the electronic display.","16.An autonomous on-road vehicle providing the effect of a large front mirror, comprising: a compartment comprising a front seat; a camera, physically coupled to the vehicle, configured to take images of an occupant who sits in the front seat; a computer configured to generate, based on the images, a video that shows a mirror effect; a communication module configured to transmit the video to a head-mounted display (HMD) worn by the occupant; and the HMD is configured to present the video to the occupant, such that the occupant sees a representation of his or her reflection when looking forward at eye level.","17.The autonomous on-road vehicle of claim 16, wherein the video presented to the occupant captures at least 30×30 degrees of the occupant's field of view, from the horizon to 30° below the horizon.","18.The autonomous on-road vehicle of claim 16, further comprising a second camera configured to take a second set of images of the outside environment in front of the occupant, the computer is further configured to generate a representation of the outside environment based on the second set of images, and the HMD is configured to present the representation of the outside environment in addition to the video that shows the mirror effect.","19.The autonomous on-road vehicle of claim 16, wherein the HMD is selected from the group comprising: a virtual reality headset, an augmented reality headset, and mixed reality headset; and wherein the camera comprises first and second cameras, located to the right and left of the occupant, respectively.","20.The autonomous on-road vehicle of claim 16, wherein the camera comprises first and second cameras, located above the level of the occupant's nose and below the level of the occupant's collarbone, respectively, and less than 80 cm away from the occupant."],[" BACKGROUND Windowless vehicles, or vehicles without a windshield, may have various benefits when it comes to safety, weight, and cost.","However, in some cases, some occupants may feel claustrophobic in such a vehicle.","Thus, there is a need for a way to make traveling in such vehicles more pleasurable for occupants who might feel somewhat unease in confined spaces.","Other occupants would like to see themselves while traveling.","Thus, there is a need to have a large front mirror that enables the occupants to see themselves."],[" SUMMARY Some aspects of this disclosure involve an autonomous on-road vehicle that provides the effect of a large front mirror.","The vehicle includes a compartment having a large mirroring element located in front of an occupant who sits in a front seat of the compartment.","The mirroring element captures a region corresponding to at least 10×10 degrees, including a region spanning from the horizon to at least 10° below the horizon of the occupant's forward field of view during normal driving.","Additionally, the mirroring element provides an effect of reflecting more than 25% of the light arriving from the occupant's direction.","In some embodiments, the vehicle has an advantage that it can increase the perceived compartment volume, which can make travelling in the vehicle more pleasurable for some people.","Other aspects of this disclosure involve an autonomous on-road vehicle that provides the effect of a large front mirror.","The vehicle includes a compartment, a camera, a computer, and a head-mounted display (HMD).","The compartment includes a front seat, the camera is physically coupled to the vehicle and takes images of an occupant who sits in the front seat, the computer generates a video that shows a mirror effect based on the images, the communication module transmits the video to the HMD that is worn by the occupant, and the HMD presents the video to the occupant, such that the occupant sees a representation of his or her reflection when looking forward at eye level."],["CROSS-REFERENCE TO RELATED APPLICATIONS This Application is a Continuation of U.S. application Ser.","No.","15/335,404, filed Oct. 26, 2016, which claims priority to U.S.","Provisional Patent Application No.","62/246,187, filed on 26 Oct. 2015, and U.S.","Provisional Patent Application No.","62/369,127, filed on 31 Jul.","2016.ACKNOWLEDGMENTS Gil Thieberger would like to thank his holy and beloved teacher, Lama Dvora-hla, for her extraordinary teachings and manifestation of wisdom, love, compassion and morality, and for her endless efforts, support, and skills in guiding him and others on their paths to freedom and ultimate happiness.","Gil would also like to thank his beloved parents for raising him exactly as they did.","BACKGROUND Windowless vehicles, or vehicles without a windshield, may have various benefits when it comes to safety, weight, and cost.","However, in some cases, some occupants may feel claustrophobic in such a vehicle.","Thus, there is a need for a way to make traveling in such vehicles more pleasurable for occupants who might feel somewhat unease in confined spaces.","Other occupants would like to see themselves while traveling.","Thus, there is a need to have a large front mirror that enables the occupants to see themselves.","SUMMARY Some aspects of this disclosure involve an autonomous on-road vehicle that provides the effect of a large front mirror.","The vehicle includes a compartment having a large mirroring element located in front of an occupant who sits in a front seat of the compartment.","The mirroring element captures a region corresponding to at least 10×10 degrees, including a region spanning from the horizon to at least 10° below the horizon of the occupant's forward field of view during normal driving.","Additionally, the mirroring element provides an effect of reflecting more than 25% of the light arriving from the occupant's direction.","In some embodiments, the vehicle has an advantage that it can increase the perceived compartment volume, which can make travelling in the vehicle more pleasurable for some people.","Other aspects of this disclosure involve an autonomous on-road vehicle that provides the effect of a large front mirror.","The vehicle includes a compartment, a camera, a computer, and a head-mounted display (HMD).","The compartment includes a front seat, the camera is physically coupled to the vehicle and takes images of an occupant who sits in the front seat, the computer generates a video that shows a mirror effect based on the images, the communication module transmits the video to the HMD that is worn by the occupant, and the HMD presents the video to the occupant, such that the occupant sees a representation of his or her reflection when looking forward at eye level.","BRIEF DESCRIPTION OF THE DRAWINGS The embodiments are herein described by way of example only, with reference to the accompanying drawings.","No attempt is made to show structural details of the embodiments in more detail than is necessary for a fundamental understanding of the embodiments.","In the drawings: FIG.","1 is a schematic illustration of components of a system configured to combine video see-through (VST) with video-unrelated-to-the-VST (VUR); FIG.","2 illustrates an HMD tracking module that measures the position of the HMD relative to the compartment; FIG.","3 illustrates a vehicle in which an occupant wears an HMD; FIG.","4 illustrates an occupant wearing an HMD and viewing large VUR and smaller VST; FIG.","5a illustrates how the VST moves to the upper left when the occupant looks to the bottom right; FIG.","5b illustrates how the VST moves to the bottom right when the occupant looks to the upper left; FIG.","6 illustrates HMD-video that includes both a non-transparent VST and video that shows the hands of the occupant and the interior of the compartment; FIG.","7 illustrates HMD-video that includes both a partially transparent VST and video that shows the hands of the occupant and the interior of the compartment; FIG.","8 illustrates HMD-video that includes a VST and partially transparent video that shows the hands of the occupant and the interior of the compartment; FIG.","9a illustrates HMD-video that includes a VUR in full FOV, a first window comprising compartment-video (CV) and a second smaller window comprising the VST; FIG.","9b illustrates HMD-video that includes VUR in full FOV, a first window comprising the CV and a second partially transparent smaller window comprising the VST; FIG.","10a illustrates HMD-video that includes VUR in full FOV, a first window comprising VST and a second smaller window comprising zoom out of the CV; FIG.","10b illustrates HMD-video that includes VUR and a partially transparent CV; FIG.","11a illustrates a FOV of a vehicle occupant when the occupant wears an HMD that presents HMD-video; FIG.","11b illustrates a FOV of a vehicle occupant when the vehicle occupant does not wear an HMD that presents the video, such as when watching an autostereoscopic display; FIG.","11c illustrates FOV of a 3D camera that is able to capture sharp images from different focal lengths; FIG.","12 is a schematic illustration of components of a system configured to enable an HMD to cooperate with a window light shading module; FIG.","13a illustrates a first mode for a shading module where an occupant sees the outside environment through the optical see-through component; FIG.","13b illustrates a second mode for a shading module where the occupant sees the outside environment through a VST; FIG.","14 illustrates a VST over a curtain; FIG.","15 illustrates a light shading module that is unfurled on the inside of the compartment; FIG.","16 illustrates a light shading module that is unfurled on the outside of the compartment; FIG.","17 is a schematic illustration of components of a video system that may be used to increase awareness of an occupant of a vehicle regarding an imminent SDRS; FIG.","18a illustrates presenting VUR to an occupant when there is no indication that an SDRS event is imminent; FIG.","18b illustrates presenting VST responsive to receiving an indication that an SDRS event is imminent (a pothole); FIG.","18c illustrates presenting VST responsive to receiving an indication that an SDRS event is imminent (a sharp turn); FIG.","19a illustrates presenting VUR and VST when there is no indication that an SDRS event is imminent; FIG.","19b illustrates presenting a larger VST responsive to receiving an indication that an SDRS event is imminent (a road bump); FIG.","19c illustrates presenting a partially transparent VST responsive to receiving an indication that an SDRS event is imminent; FIG.","20a illustrates a smart glass shading module when there is no indication that an SDRS event is imminent; FIG.","20b illustrates the smart glass shading module when there is an indication that an SDRS event is imminent; FIG.","21a and FIG.","21b illustrate vehicles with an SAEDP in their compartment were an occupant uses an HMD to receive a representation of the outside environment; FIG.","22 illustrates a vehicle with an SAEDP in the vehicle's compartment with displays; FIG.","23 illustrates how an SAEDP protects the occupant in a side collision; FIG.","24a and FIG.","24b illustrate a vehicle with a motor configured to move a nontransparent SAEDP to cover a side window; FIG.","25a and FIG.","25b illustrate a vehicle with a motor configured to move a front SAEDP between first and second states; FIG.","26a illustrates an SAEDP mounted to the front of a vehicle at eye level of an occupant of the vehicle; FIG.","26b illustrates an outer SAEDP that includes two air bags; FIG.","27a and FIG.","27b illustrate a motorized external SAEDP that can move between first and second states multiple times; FIG.","28 illustrates a vehicle compartment in which an occupant may lay down; FIG.","29 illustrates a vehicle with a front mirror; FIG.","30a illustrates one example of a configuration of a plurality of beams located in the left side of the vehicle; FIG.","30b illustrates one example of a configuration of a plurality of beams located in the front of the vehicle; and FIG.","31a and FIG.","31b are schematic illustrations of computers able to realize one or more of the embodiments discussed herein.","DETAILED DESCRIPTION The following are definitions of various terms that may be used to describe one or more of the embodiments in this disclosure.","The terms “autonomous on-road vehicle” and “autonomous on-road manned vehicle” refer to cars and motorcycles designed to drive on public roadways utilizing automated driving of level 3 and above according to SAE International standard J3016 “Taxonomy and Definitions for Terms Related to On-Road Motor Vehicle Automated Driving Systems”.","For example, the autonomous on-road vehicle may be a level 3 vehicle, in which within known, limited environments, drivers can safely turn their attention away from driving tasks; the autonomous on-road vehicle may be a level 4 vehicle, in which the automated system can control the vehicle in all but a few environments; and/or the autonomous on-road vehicle may be a level 5 vehicle, in which no human intervention is required and the automatic system can drive to any location where it is legal to drive.","Herein, the terms “autonomous on-road vehicle” and “self-driving on-road vehicle” are equivalent terms that refer to the same.","The term “autonomous on-road vehicle” does not include trains, airplanes, boats, and armored fighting vehicles.","An autonomous on-road vehicle utilizes an autonomous-driving control system to drive the vehicle.","The disclosed embodiments may use any suitable known and/or to be invented autonomous-driving control systems.","The following three publications describe various autonomous-driving control systems that may be utilized with the disclosed embodiments: (i) Paden, Brian, et al.","“A Survey of Motion Planning and Control Techniques for Self-driving Urban Vehicles.” arXiv preprint arXiv:1604.07446 (2016); (ii) Surden, Harry, and Mary-Anne Williams.","“Technological Opacity, Predictability, and Self-Driving Cars.” Predictability, and Self-Driving Cars (Mar.","14, 2016) (2016); and (iii) Gonzalez, David, et al.","“A Review of Motion Planning Techniques for Automated Vehicles.” IEEE Transactions on Intelligent Transportation Systems 17.4 (2016): 1135-1145.Autonomous-driving control systems usually utilize algorithms such as machine learning, pattern recognition, neural network, machine vision, artificial intelligence, and/or probabilistic logic to calculate on the fly the probability of an imminent collision, or to calculate on the fly values that are indicative of the probability of an imminent collision (from which it is possible to estimate the probability of an imminent collision).","The algorithms usually receive as inputs the trajectory of the vehicle, measured locations of at least one nearby vehicle, information about the road, and/or information about environmental conditions.","Calculating the probability of an imminent collision is well known in the art, also for human driven vehicles, such as the anticipatory collision system disclosed in U.S. Pat.","No.","8,041,483 to Breed.","In order to calculate whether a Sudden Decrease in Ride Smoothness (SDRS) event is imminent, the autonomous-driving control system may compare parameters describing the state of the vehicle at time t1 with parameters describing the state of the vehicle at time t2 that is shortly after t1.If the change in one or more of the parameters reaches a threshold (such as deceleration above a certain value, change of height in the road above a certain value, and/or an angular acceleration above a certain value) then it may be determined that an SDRS event is imminent.","An “occupant” of a vehicle, as the term is used herein refers to a person that is in the vehicle when it drives.","The term “occupant” refers to a typical person having a typical shape, such as a 170 cm tall human (herein “cm” refers to centimeters).","An occupant may be a driver, having some responsibilities and/or control regarding the driving of the vehicle (e.g., in a vehicle that is not completely autonomous), or may be a passenger.","When an embodiment refers to “the occupant of the vehicle”, it may refer to one of the occupants of the vehicle.","Stating that a vehicle has an “occupant” should not be interpreted that the vehicle necessarily accommodates only one occupant at a time, unless that is explicitly stated, such as stating that the vehicle is “designed for a single occupant”.","Herein, a “seat” may be any structure designed to hold an occupant travelling in the vehicle (e.g., in a sitting and/or reclining position).","A “front seat” is a seat that positions an occupant it holds no farther from the front of the vehicle than any other occupants of the vehicle are positioned.","Herein, sitting in a seat also refers to sitting on a seat.","Sitting in a seat is to be interpreted in this disclosure as occupying the space corresponding the seat, even if the occupant does so by assuming a posture that does not necessarily correspond to sitting.","For example, in some vehicles the occupant may be reclined or lying down, and in other vehicles the occupant may be more upright, such as when leaning into the seat in a half standing half seating position similar to leaning into a Locus Seat by Focal Upright LLC.","The interchangeable terms “environment outside the vehicle” and “outside environment” refer to the environment outside the vehicle, which includes objects that are not inside the vehicle compartment, such as other vehicles, roads, pedestrians, trees, buildings, mountains, the sky, and outer space.","A sensor “mounted to the vehicle” may be connected to any relevant part of the vehicle, whether inside the vehicle, outside the vehicle, to the front, back, top, bottom, and/or to a side of the vehicle.","A sensor, as used herein, may also refer to a camera.","The term “camera” refers herein to an image-capturing device that takes images of an environment.","For example, the camera may be based on at least one of the following sensors: a CCD sensor, a CMOS sensor, a near infrared (NIR) sensor, an infrared sensor (IR), and a device based on active illumination such as a LiDAR.","The term “video” refers to a series of images that may be provided in a fixed rate, variable rates, a fixed resolution, and/or dynamic resolutions.","The use of a singular “camera” should be interpreted herein as “one or more cameras”.","Thus, when embodiments herein are described as including a camera that captures video and/or images of the outside environment in order to generate a representation of the outside environment, the representation may in fact be generated based on images and/or video taken using multiple cameras.","Various embodiments described herein involve providing an occupant of the vehicle with representation of the outside environment, generated by a computer and/or processor, based on video taken by a camera.","In some embodiments, video from a single camera (e.g., which may be positioned on the exterior of the vehicle at eye level), may be sent to presentation to the occupant by the processor and/or computer following little, if any, processing.","In other embodiments, video from a single camera or multiple cameras is processed in various ways, by the computer and/or processor, in order to generate the representation of the outside environment that is presented to the occupant.","Methods and systems for stitching live video streams from multiple cameras, stitching live video streams with database objects and/or other video sources, transforming a video stream or a stitched video stream from one point of view to another point of view (such as for generating a representation of the outside environment for an occupant at eye level, or for generating a compartment view for a person standing outside the compartment), tracking the position of an HMD relative to a compartment, and presenting rendered images that are perfectly aligned with the outside world—are all known in the art of computer graphics, video stitching, image registration, and real-time 360° imaging systems.","The following publications are just a few examples of reviews and references that describe various ways to perform the video stitching, image registration, tracking, and transformations, which may be utilized by the embodiments disclosed herein: (i) Wang, Xiaogang.","“Intelligent multi-camera video surveillance: A review.” Pattern recognition letters 34.1 (2013): 3-19.","(ii) Szeliski, Richard.","“Image alignment and stitching: A tutorial.” Foundations and Trends® in Computer Graphics and Vision 2.1 (2006): 1-104.","(iii) Tanimoto, Masayuki.","“FTV: Free-viewpoint television.” Signal Processing: Image Communication 27.6 (2012): 555-570.","(iv) Ernst, Johannes M., Hans-Ullrich Doehler, and Sven Schmerwitz.","“A concept for a virtual flight deck shown on an HMD.” SPIE Defense+ Security.","International Society for Optics and Photonics, 2016.","(v) Doehler, H-U., Sven Schmerwitz, and Thomas Lueken.","“Visual-conformal display format for helicopter guidance.” SPIE Defense+ Security.","International Society for Optics and Photonics, 2014.","(vi) Sanders-Reed, John N., Ken Bernier, and Jeff Güell “Enhanced and synthetic vision system (ESVS) flight demonstration.” SPIE Defense and Security Symposium.","International Society for Optics and Photonics, 2008.And (vii) Bailey, Randall E., Kevin J. Shelton, and J. J. Arthur III.","“Head-worn displays for NextGen.” SPIE Defense, Security, and Sensing.","International Society for Optics and Photonics, 2011.A video that provides “representation of the outside environment” refers to a video that enables the average occupant, who is familiar with the outside environment, to recognize the location of the vehicle in the outside environment from watching the video.","In one example, the average occupant is a healthy 30 years old human who is familiar with the outside environment, and the threshold for recognizing a video as a “representation of the outside environment” is at least 20 correct recognitions of the outside environment out of 30 tests.","Herein, sentences such as “VST that represents a view of the outside environment from the point of view of the occupant”, or “VST representation of the outside environment, which could have been seen from the point of view of the occupant” refer to a video representing at least a portion of the outside environment, with a deviation of less than ±20 degrees from the occupant's point of view of the outside environment, and zoom in the range of 30% to 300% (assuming the occupant's unaided view is at 100% zoom level).","The VST may be generated based on at least one of the following resources: a video of the outside environment that is taken in real-time, a video of the outside environment that was taken in the past and is played/processed according to the trajectory of the vehicle, a database of the outside environment that is utilized for rendering the VST according to the trajectory of the vehicle, and/or a video that is rendered as function of locations of physical objects identified in the outside environment using detection and ranging systems such as RADAR and/or LIDAR.","Moreover, the term “video see-through (VST)” covers both direct representations of the outside environment, such as a video of the outside environment, and/or enriched video of the outside environment, such as captured video and/or rendered video of the outside environment presented together with one or more layers of virtual objects, as long as more than 20% of the average vehicle occupants, who are familiar with the outside environment, would be able to determine their location in the outside environment, while the vehicle travels, without using a map, and with a margin of error below 200 meters.","However, it is noted that showing a map that indicates the location of the vehicle on the driving path (such as from the start to the destination) is not considered herein as equivalent to the VST, unless the map includes all of the following properties: the map shows images of the path, the images of the path capture at least 5 degrees of the occupant's FOV at eye level, and the images of the path reflect the dynamics of the vehicle and change in a similar manner to a video taken by a camera mounted to the vehicle and directed to the outside environment.","Herein, “field of view (FOV) of the occupant to the outside environment” refers to the part of the outside environment that is visible to the occupant of a vehicle at a particular position and orientation in space.","In one example, in order for an occupant-tracking module to calculate the FOV to the outside environment of an occupant sitting in a vehicle compartment, the occupant-tracking module determines the position and orientation of the occupant's head.","In another example, in order for an occupant-tracking module to calculate the FOV of an occupant sitting in a vehicle compartment, the occupant-tracking module utilizes an eye tracker.","It is noted that sentences such as “a three dimensional (3D) video see-through (VST) that represents a view of the outside environment, which could have been seen from the point of view of the occupant had the FOV not been obstructed by at least a portion of the nontransparent element” cover also just one or more portions of the FOV, and are to be interpreted as “a three dimensional (3D) video see-through (VST) that represents a view of at least a portion of the outside environment, which could have been seen from the point of view of the occupant had at least some of the FOV not been obstructed by at least a portion of the nontransparent element”.","The term “display” refers herein to any device that provides a human user with visual images (e.g., text, pictures, and/or video).","The images provided by the display may be two-dimensional or three-dimensional images.","Some non-limiting examples of displays that may be used in embodiments described in this disclosure include: (i) screens and/or video displays of various devices (e.g., televisions, computer monitors, tablets, smartphones, or smartwatches), (ii) headset- or helmet-mounted displays such as augmented-reality systems (e.g., HoloLens), virtual-reality systems (e.g., Oculus rift, HTC Vive, or Samsung GearVR), and mixed-reality systems (e.g., Magic Leap), and (iii) image projection systems that project images on a occupant's retina, such as: Virtual Retinal Displays (VRD) that create images by scanning low power laser light directly onto the retina, or light-field technologies that transmit light rays directly into the eye.","Various embodiments may include a reference to elements located at eye level.","The “eye level” height is determined according to an average adult occupant for whom the vehicle was designed, who sits straight and looks to the horizon.","Sentences in the form of “an element located at eye level of an occupant who sits in a vehicle” refer to the element and not to the occupant.","The occupant is used in such sentences in the context of “eye level”, and thus claims containing such sentences do not require the existence of the occupant in order to construct the claim.","Sentences such as “SAEDP located at eye level”, “stiff element located at eye level”, and “crumple zone located at eye level” refer to elements that are located at eye level, but may also extended to other levels, such as from sternum level to the roof level, from floor level to eye level, and/or from floor level to roof level.","For example, an SAEDP located at an eye level can extend from sternum level to above the occupant's head, such that at least a portion of the SAEDP is located at the eye level.","Herein, “normal driving” refers to typical driving conditions, which persist most of the time the vehicle is in motion.","During normal driving the probability of a collision is below a threshold that when reached typically involves one or more of the following actions: deployment of safety devices that are not usually deployed (e.g., inflating airbags), taking evasive action to avoid a collision, and warning occupants of the vehicle about an imminent event that may cause a Sudden Decrease in Ride Smoothness (SDRS).","A Shock-Absorbing Energy Dissipation Padding (SAEDP) is an element that may be used to cushion impact of a body during a collision or during SDRS events.","Various types of SAEDPs may be used in embodiments described herein, such as passive materials, airbags, and pneumatic pads.","Some examples of passive materials that may be used for the SAEDP in one or more of the disclosed embodiments include one or more of the following materials: CONFOR® foam by Trelleborg Applied Technology, Styrofoam by The Dow Chemical Company, Micro-Lattice Materials and/or Metallic Microlattices (such as by HRL Laboratories in collaboration with researchers at University of California and Caltech), non-Newtonian energy Absorbing materials (such as D3O® by D3O lab, and DEFLEXION™ by Dow Corning®), Sorbothane® by Sorbothane Incorporated, and padding that includes compression cells and/or shock absorbers of the Xenith LLC type (such as described in U.S. Pat.","No.","8,950,735 and US patent application num.","20100186150), and materials that include rubber such as a sponge rubber.","The term “stiff element” refers to a material having stiffness and impact resistance equal or greater than that of glazing materials for use in motor vehicles as defined in the following two standards: (i) “American National Standard for Safety Glazing Materials for Glazing Motor Vehicles and Motor Vehicle Equipment Operating on Land Highways-Safety Standard” ANSI/SAE Z26.1-1996, and (ii) The Society of Automotive Engineers (SAE) Recommended Practice J673, revised April 1993, “Automotive Safety Glasses” (SAE J673, rev.","April 93).","The term “stiff element” in the context of low speed vehicles refers to a material having stiffness and impact resistance equal or greater than that of glazing materials for use in low speed motor vehicles as defined in Federal Motor Vehicle Safety Standard 205—Glazing Materials (FMVSS 205), from 49 CFR Ch.","V (10-1-04 Edition).","The stiff element may be transparent (such as automotive laminated glass, or automotive tempered glass) or nontransparent (such as fiber-reinforced polymer, carbon fiber reinforced polymer, steel, or aluminum).","Herein, a nontransparent element is defined as an element having Visible Light Transmittance (VLT) between 0% and 20%, which does not enable the occupant to recognize what lies on the other side of it.","For example, a thick ground glass usually allows light to pass through it but does not let the occupant recognize the objects on the other side of it, unlike plain tinted glass that usually lets the occupant recognize the objects on the other side of it, even when it features VLT below 10%.","The nontransparent element includes an opaque element having VLT of essentially 0% and includes a translucent element having VLT below 20%.","VLT is defined as the amount of incident visible light that passes through the nontransparent element, where incident light is defined as the light that strikes the nontransparent element.","VLT is also known as Luminous Transmittance of a lens, a light diffuser, or the like, and is defined herein as the ratio of the total transmitted light to the total incident light.","The common clear vehicle windshield has a VLT of approximately 85%, although US Federal Motor Vehicle Safety Standard No.","205 allows the VLT to be as low as 70%.","Sentences such as “video unrelated to the VST (VUR)” mean that an average occupant would not recognize the video as a representation of the outside environment.","In some embodiments, the content of the VUR does not change as function of the position of the occupant's head, which means that the point of view from which the occupant watches the VUR does not change essentially when the occupant's head moves.","Herein, stabilization effects, image focusing, dynamic resolution, color corrections, and insignificant changes to less than 10% of the frame as function of the position of the occupant's head—are still considered as content that does not change as function of the position of the occupant's head.","Examples of such content (common in the year 2016) include cinema movies, broadcast TV shows, standard web browsers, and Microsoft Office 2016 applications (such as Word, Excel and PowerPoint).","Herein, a “crumple zone” refers to a structure designed to slow down inertia and absorb energy from impact during a traffic collision by controlled deformation.","The controlled deformation absorbs some of the impact within the outer parts of the vehicle, rather than being directly transferred to the occupants, while also preventing intrusion into and/or deformation of the compartment.","Crumple zone may be achieved by various configurations, such as one or more of the following exemplary configurations: (i) by controlled weakening of sacrificial outer parts of the vehicle, while strengthening and increasing the stiffness of the inner parts of the vehicle, such as by using more reinforcing beams and/or higher strength steels for the compartment; (ii) by mounting composite fiber honeycomb or carbon fiber honeycomb outside the compartment; (iii) by mounting an energy absorbing foam outside the compartment; and/or (iv) by mounting an impact attenuator that dissipates impact.","In order to enable an occupant of a vehicle to view the outside environment, without needing to look out of a physical window, some aspects of this disclosure involve systems that combine video see-through (VST) with video-unrelated-to-the-VST (VUR).","In one embodiment, a system configured to combine video see-through (VST) with video-unrelated-to-the-VST (VUR) includes a head-mounted display (HMD), a camera, an HMD tracking module and a computer.","The HMD is configured to be worn by an occupant of a compartment of a moving vehicle and to present an HMD-video to the occupant.","The camera, which is mounted to the vehicle, is configured to take video of the outside environment (Vout).","The HMD tracking module is configured to calculate position of the HMD relative to the compartment, based on measurements of a sensor.","The computer is configured to receive a location of a video see-through window (VSTW) in relation to the compartment, and to calculate, based on the position of the HMD relative to the compartment, a window-location for the VSTW on the HMD-video.","Additionally, the computer is further configured to generate, based on the window-location and the Vout, the VST that represents a view of the outside environment from the point of view of the occupant.","The computer is also configured to generate the HMD-video based on combining the VUR with the VST in the window-location.","It is to be noted that the content of the VUR is unrelated to the video taken by the camera.","In one embodiment, a system configured to combine video see-through (VST) with video-unrelated-to-the-VST (VUR) includes at least the following components: a head-mounted display (HMD), such as HMD 15, a camera (e.g., camera 12), an HMD tracking module 27, and a computer 13.FIG.","1 provides a schematic illustration of at least some of the relationships between the components mentioned above.","The HMD 15 is configured to be worn by an occupant of a compartment of a moving vehicle and to present an HMD-video 16 to the occupant.","In one embodiment, the HMD 15 is an augmented-reality (AR) HMD.","In another embodiment, the HMD 15 is a virtual reality (VR) HMD.","Optionally, in this embodiment, the system further comprises a video camera mounted to the VR HMD, and the VST video comprises video of the compartment received from the video camera mounted to the VR HMD.","In yet another embodiment, the HMD 15 is a mixed reality HMD.","The term “Mixed Reality” (MR) as used herein involves a system that is able to combine real world data with virtual data.","Mixed Reality encompasses Augmented Reality and encompasses Virtual Reality that does not immerse its user 100% of the time in the virtual world.","Examples of mixed reality HMDs include, but are not limited to, Microsoft HoloLens HMD and MagicLeap HMD.","The camera 12, which is mounted to the vehicle, is configured to take video of the outside environment (Vout).","Optionally, the data captured by the camera comprises 3D data.","For example, the camera may be based on at least one of the following sensors: a CCD sensor, a CMOS sensor, a near infrared (NIR) sensor, an infrared sensor (IR), and a device based on active illumination such as a LiDAR.","The HMD tracking module 27 is configured to calculate position of the HMD 15 relative to the compartment, based on measurements of a sensor.","In different embodiments, the HMD tracking module 27 may have different configurations.","In one embodiment, the sensor comprises first and second Inertial Measurement Units (IMUs).","In this embodiment, the first IMU is physically coupled to the HMD 15 and is configured to measure a position of the HMD 15, and the second IMU is physically coupled to the compartment and is configured to measure a position of the compartment.","The HMD tracking module 27 is configured to calculate the position of the HMD 15 in relation to the compartment based on the measurements of the first and second IMUs.","In another embodiment, the sensor comprises an Inertial Measurement Unit (IMU) and a location measurement system.","In this embodiment, the IMU is physically coupled to the HMD 15 and is configured to measure an orientation of the HMD 15.The location measurement system is physically coupled to the compartment and is configured to measure a location of the HMD in relation to the compartment.","The HMD tracking module 27 is configured to calculate the position of the HMD 15 in relation to the compartment based on the measurements of the IMU and the location measurement system.","Optionally, the location measurement system measures the location of the HMD 15 in relation to the compartment based on at least one of the following inputs: a video received from a camera that captures the HMD 15, a video received from a stereo vision system, measurements of magnetic fields inside the compartment, wireless triangulation measurements, acoustic positioning measurements, and measurements of an indoor positioning systems.","FIG.","2 illustrates one embodiment in which the HMD tracking module 27 is physically coupled to the compartment and is configured to measure the position of the HMD relative to the compartment.","The HMD tracking module 27 may utilize a passive camera system, an active camera system that captures reflections of a projected grid, and/or a real-time locating systems based on microwaves and/or radio waves.","The computer 13 is configured to receive a location of a video see-through window (VSTW) in relation to the compartment, and to calculate, based on the position of the HMD relative to the compartment, a window-location for the VSTW on the HMD-video.","The computer 13 is also configured to generate, based on the window-location and the Vout, the VST that represents a view of the outside environment from the point of view of the occupant.","Optionally, the VST is rendered as a 3D video content.","Additionally, the computer 13 is further configured to generate the HMD-video 16 based on combining the VUR with the VST in the window-location.","The computer 13 may use various know in the art computer graphics functions and/or libraries to generate the VST, transform the VST to the occupant's point of view, render the 3D video content, and/or combine the VUR with the VST.","In one embodiment, the content of the VUR does not change when the occupant moves the head, and the content of the VUR is unrelated to the video taken by the camera.","Additionally, the content of the VUR is generated based on data that was received more than 2 seconds before the HMD-video 16 is displayed to the occupant.","Some examples of the VUR include a video stream of at least one of the following types of content: a recorded television show, a computer game, an e-mail, and a virtual computer desktop.","FIG.","3 illustrates one embodiment in which the occupant 14 wears an HMD 15.The HMD 15 provides video to the occupant 14 through the display of the HMD 15.The vehicle includes a camera 12 that takes video of the outside environment 11a and processes it in a manner suitable for the location of the occupant.","The processed video is provided to the occupant's display in the HMD 15 as a VSTW and the position of the VSTW is calculated in relation to the compartment of the vehicle and moves with the compartment.","While the vehicle is in motion, the VSTW change its content to represent the outside environment 11a of the vehicle.","Whereas the video-unrelated-to-the-VST doesn't change when the occupant moves his head.","The computer is configured to receive a location of a VSTW in relation to the compartment, and to calculate, based on the position of the occupant's head, a window-location for the VSTW on the video.","FIG.","4 illustrates one embodiment in which the occupant 44 wears HMD 45 and views large VUR 40 and smaller VST 41a.","The VUR 40 does not change when the occupant's head 44 moves.","The VSTW presents video of the street based on video taken by the camera that is mounted to the vehicle.","The location of the video-see-through window in relation to the compartment does not change when the occupant 44 moves his/her head in order to imitate a physical window that does not change its position relative to the compartment when the occupant's head moves.","FIG.","5a illustrates how, in one embodiment, the VST moves to the upper left when the occupant 44 looks to the bottom right.","FIG.","5b illustrates how the VST moves to the bottom right when the occupant 44 looks to the upper left, while the VUR moves with the head.","In both cases, the VUR moves with the head while the location of the VST changes according to the movement of the head relative to the compartment as measured by the HMD tracking module 27.In some embodiments, the content of the VUR may be augmented-reality content, mixed-reality content, and/or virtual-reality content rendered to correspond to the occupant's viewing direction.","In this embodiment, the VUR is unrelated to the video taken by the camera.","In one example, the VUR may include a video description of a virtual world in which the occupant may be playing a game (e.g., represented by an avatar).","Optionally, in this example, most of the features of the virtual world are different from the view of the outside of the vehicle (as seen from the occupant's viewing direction).","For example, the occupant may be driving in a city, while the virtual world displays woods, a meadow, or outer space.","In another example, the VUR may include augmented reality content overlaid above a view of the inside of the compartment.","In addition to the components described above, in some embodiments, the system may include a second camera that is mounted to the HMD and is configured to take video of the compartment (Vcomp).","In this embodiment, the computer is further configured to generate a compartment-video (CV), based on Vcomp and a location of a compartment-video window (CVW) in relation to the HMD-video (e.g., HMD-video 16), and to generate the HMD-video also based on the CV in the CVW, such that the HMD-video combines the VUR with the VST in the window-location and with the CV in the CVW.","There are various ways in which the CVW may be incorporated into the HMD-video.","Some examples of these approaches are illustrated in the following figures.","FIG.","6 illustrates HMD-video that includes both a non-transparent VST 55 in the window-location and a CV 56 that shows the hands of the occupant and the interior of the compartment in the CVW.","FIG.","7 illustrates HMD-video that includes both a partially transparent VST 57 in the window-location and the CV 56 that shows the hands of the occupant and the interior of the compartment in the CVW.","FIG.","8 illustrates HMD-video that includes a VST 58 and partially transparent CV 59.The figure illustrates that the occupant sees the outside environment in full field-of-view (FOV), while on top of it there is a partially transparent image (illustrated as dotted image) of the compartment and the hands of the occupant, in order to help the occupant not to hit things in the compartment.","FIG.","9a illustrates HMD-video that includes a VUR 70 in full FOV, a first window comprising the CV 71 in the CVW and a second smaller window comprising the VST 72 in the window-location.","FIG.","9b illustrates HMD-video that includes VUR 70 in full FOV, a first window comprising the CV 71 in the CVW and a second partially transparent smaller window comprising the VST 73 in the window-location.","FIG.","10a illustrates HMD-video that includes VUR 70 in full FOV, a first window comprising VST 75 in the window-location and a second smaller window comprising zoom out of the CV 76 in the CVW.","Optionally, the cabin view in the zoom out is smaller than in reality, and may enable the occupant to orient in the cabin.","Optionally, the occupant may move the CVW, as illustrated in FIG.","10a where the zoom out of the CV in the CVW is somewhat above its location in reality.","FIG.","10b illustrates HMD-video that includes VUR 70 and a partially transparent CV 72.Here a first occupant sees the VUR in full field-of-view (FOV), and on top of it there is a partially transparent image of the compartment and a second occupant that sits to the left of the first occupant, which may help the first occupant not to hit the second occupant.","There may be various ways in which the system determines the location and/or size of the VSTW.","In one embodiment, the VSTW is pinned to at least one of the following locations: a specific physical location and a location of an object in the compartment, such that the location of the VSTW in relation to the compartment does not change when the occupant moves his/her head with the HMD 15 as part of watching the HMD-video 16 and without commanding the VSTW to move in relation to the compartment.","In another embodiment, the system includes a user interface configured to receive a command from the occupant to move and/or resize the VSTW in relation to the compartment.","In one example, the command is issued through a voice command (e.g., saying “move VST to the bottom”).","In another example, the command may be issued by making a gesture, which is detected by a gesture control module in the compartment and/or on a device of the occupant (e.g., as part of the HMD).","Optionally, in this embodiment, the computer is further configured to: update the window-location based on the command from the occupant, and generate an updated VST based on the updated window-location and the video taken by the camera.","In this embodiment, the VST and the updated VST present different VSTW locations and/or dimensions in relation to the compartment.","Optionally, the HMD is configured not to present any part of the VST to the occupant when the window-location is not in the field of view presented to the occupant through the HMD.","In yet another embodiment, the system may further include a video analyzer configured to identify an Object Of Interest (OOI) in the outside environment.","For example, the OOI of interest may be a certain landmark (e.g., a building), a certain object (e.g., a store or a certain model of automobile), or a person.","In this embodiment, the computer is further configured to receive, from the video analyzer, an indication of the position of the OOI, and to track the OOI by adjusting the window-location according to the movements of the vehicle, such that the OOI is visible via the VST.","Optionally, the HMD is configured not to present any part of the VST to the occupant when the window-location is not in the field of view presented to the occupant through the HMD.","The VST that represents the view of the outside environment from the point of view of the occupant, in some embodiments, does not necessarily match the video taken by the cameras.","In one embodiment, the VST may utilize image enhancement techniques to compensate for outside lighting conditions, to give an occupant an experience similar to looking out through a conventional vehicle window but without the view being distorted by raindrops or dirt on the window, and/or to improve the visual impression of the outside environment e.g.","by showing background images which are different from those retrievable from the outside environment.","Additionally or alternatively, the VST may mimic the outside environment, alter the outside environment, and/or be completely different from what can be seen on the outside environment.","The VST may be focused on providing visual information that makes the travelling more fun.","The vehicle may provide different styles of the outside environment to different occupants in the vehicle, such that a first VST provided to a first occupant may mimic the outside environment, while a second VST provided to a second occupant may alter the outside environment and/or be completely different from the outside environment, optionally for comfort enhancement and/or entertainment.","In some embodiments, the VST is informative, and aids at least some of the occupants to determine the location of the vehicle in the environment.","In one embodiment, at least some of those occupants could not determine their location without the VST.","In one example, less than 20% of average vehicle occupants, who are familiar with the outside environment, are able to determine their real location in the outside environment by watching the VUR, without using a map, with a margin of error that is less than 100 meters, and while the vehicle travels; while more than 20% of the average vehicle occupants, who are familiar with the outside environment, are able to determine their real location in the outside environment by watching the VST, without using a map, and with a margin of error that is less than 100 meters, and while the vehicle travels.","FIG.","11a illustrates a FOV in the context of presented video and terminology used herein.","The vehicle occupant 200 wears an HMD 201 that presents HMD-video (such as HMD-video 16).","The HMD-video may be presented at a single focal plane, or at multiple focal planes, depending on the characteristics of the HMD 201 (when the occupant focuses on a certain focal plane, then his/her point of gaze is said to be on the certain focal plane).","In addition, the presented objects may be two-dimensional (2D) virtual objects and/or three-dimensional (3D) virtual objects that may also be referred to as holographic objects.","Element 204 represents the location of a nontransparent element fixed to the vehicle compartment.","In one example, the HMD 201 is a holographic HMD, such as Microsoft HoloLens, which can present content displayed on a series of focal planes that are separated by some distance.","The virtual objects may be presented before the nontransparent element (e.g., polygons 202, 203), essentially on the nontransparent element 204, and/or beyond the nontransparent element (e.g., polygons 205, 206).","As a result, the occupant's gaze distance may be shorter than the distance to the nontransparent element (e.g., distance to polygons 202, 203), essentially equal to the distance to the nontransparent element 204, and/or longer than the distance to the nontransparent element (e.g., distance to polygons 205, 206).","Polygon 207 represents a portion of the presented video at eye level of the vehicle occupant, which in one example is within ±7 degrees from the horizontal line of sight.","Although the figure illustrates overlapping FOVs of polygons 202, 203, 204, and 205, the HMD may show different objects, capturing different FOVs, at different focal planes.","In one example, the HMD may project an image throughout a portion of, or all of, a display volume.","Further, a single object such as a vehicle could occupy multiple volumes of space.","According to the terminology used herein, the nontransparent element 204 is said to be located on FOV overlapping the FOV of polygons 205 and 203 because polygons 203, 204, 205 share the same FOV.","FOV of polygon 206 is contained in the FOV of polygon 204, and FOV of polygon 207 intersects the FOV of polygon 204.FOV of polygon 203 is before the nontransparent element 204 and therefore may hide the nontransparent element 204 partially or entirely, especially when utilizing a multi-focal plane HMD.","FIG.","11b illustrates a FOV in the context of the presented video, where the vehicle occupant 210 does not wear an HMD that presents the video, such as when watching an autostereoscopic display.","The autostereoscopic display is physically located on plane 214 and the presented video may be presented at a single focal plane, or at multiple focal planes, depending on the characteristics of the autostereoscopic display.","In one example, the autostereoscopic display is a holographic display, such as SeeReal Technologies holographic display, where the presented video may present virtual objects before the focal plane of the autostereoscopic display (e.g., planes 212, 213), essentially on the focal plane of the autostereoscopic display 214, and/or beyond the focal plane of the autostereoscopic display (e.g., planes 215, 216).","As a result, the occupant's gaze distance may be shorter than the distance to the autostereoscopic display (e.g., planes 212, 213), essentially equal to the distance to the autostereoscopic display 214, and/or longer than the distance to the autostereoscopic display (e.g., planes 215, 216).","The term “autostereoscopic” includes technologies such as automultiscopic, glasses-free 3D, glassesless 3D, parallax barrier, integral photography, lenticular arrays, Compressive Light Field Displays, holographic display based on eye tracking, color filter pattern autostereoscopic display, volumetric display that reconstructs light field, integral imaging that uses a fly's-eye lens array, and/or High-Rank 3D (HR3D).","FIG.","11c illustrates FOV of a 3D camera that is able to capture sharp images from different focal lengths.","In some embodiments, the vehicle and/or the HMD utilize at least one Inertial Measurement Unit (IMU), and the system utilizes an Inertial Navigation System (INS) to compensate imperfections in the IMU measurements.","An INS typically has one or more secondary navigation sensors that provide direct measurements of the linear velocity, position and/or orientation of the vehicle.","These secondary navigation sensors could be anything from stereo vision systems, to GPS receivers, to digital magnetic compasses (DMCs) or any other type of sensor that could be used to measure linear velocity, position and/or orientation.","In one example, the information from these secondary navigation sensors is incorporated into the INS using an Extended Kalman Filter (EKF).","The EKF produces corrections that are used to adjust the initial estimations of linear velocity, position and orientation that are calculated from the imperfect IMU measurements.","Adding secondary navigation sensors into an INS can increase its ability to produce accurate estimations of the linear velocity, position and orientation of the vehicle over long periods of time.","In one embodiment, the system utilizes domain specific assumptions in order to reduce drift of an INS used to calculate the HMD spatial position in relation to the compartment.","More specifically, the following methods may be used to reduce or correct drift.","Such methods generally fall in the categories of using sensor fusion and/or domain specific assumptions.","(i) Sensor fusion refers to processes in which signals from two or more types of sensors are used to update and/or maintain the state of a system.","In the case of INS, the state generally includes the orientation, velocity and displacement of the device measured in a global frame of reference.","A sensor fusion algorithm may maintain this state using IMU accelerometer and gyroscope signals together with signals from additional sensors or sensor systems.","There are many techniques to perform sensor fusion, such as Kalman filter and particle filter.","One example of periodically correcting drift is to use position data from a triangulation positioning system relative to the compartment.","Such systems try to combine the drift free nature of positions obtained from the triangulation positioning system with the high sampling frequency of the accelerometers and gyroscopes of the IMU.","Roughly speaking, the accelerometer and gyroscope signals are used to ‘fill in the gaps’ between successive updates from the triangulation positioning system.","Another example of reducing the drift is using a vector magnetometer that measures magnetic field strength in a given direction.","The IMU may contain three orthogonal magnetometers in addition to the orthogonal gyroscopes and accelerometers.","The magnetometers measure the strength and direction of the local magnetic field, allowing the north direction to be found.","(ii) In some embodiments, it is possible to make domain specific assumptions about the movements of the occupant and/or the vehicle.","Such assumptions can be used to minimize drift.","One example in which domain specific assumptions may be exploited is the assumption that when the vehicle accelerates or decelerates significantly, the HMD accelerates or decelerates essentially the same as the vehicle, allowing HMD drift in velocity to be periodically corrected based on a more accurate velocity received from the autonomous-driving control system of the vehicle.","Another example in which domain specific assumptions may be exploited is the assumption that when the vehicle accelerates or decelerates significantly, the HMDs of two occupants travelling in the same vehicle accelerate or decelerate essentially the same, allowing HMD drifts to be periodically corrected based on comparing the readings of the two HMDs.","Still another example in which domain specific assumptions are exploited is the assumption that the possible movement of an HMD of a belted occupant is most of the time limited to a portion of the compartment, allowing HMD drifts to be periodically corrected based on identifying when the HMD exceeds beyond that portion of the compartment.","In one example, it may be desirable to adjust the position of displaying a virtual object in response to relative motion between the vehicle and the HMD so that the virtual object would appear stationary in location.","However, the HMD IMU may indicate that the HMD is moving even when the detected motion is a motion of the vehicle carrying the HMD.","In order to distinguish between motion of the HMD caused by the vehicle and motion of the HMD relative to the vehicle, non-HMD sensor data may be obtained by the HMD from sensor such as an IMU located in the vehicle and/or the GPS system of the vehicle, and the motion of the vehicle may be subtracted from the motion of the HMD in order to obtain a representation of the motion of the HMD relative to the vehicle.","By differentiating movements of the HMD caused by the occupant motion compared to movements caused by the vehicle motion, the rendering of the virtual object may be adjusted for the relative motion between the HMD and the vehicle.","Using the nontransparent element, instead of a transparent glass window that provides the same FOV to the outside environment, may provide various benefits, such as: (i) reduced manufacturing cost of the vehicle compared to a similar vehicle having instead of the nontransparent element a transparent glass window that provides the same FOV to the outside environment as provided by the 3D display device, (ii) reduced weight of the vehicle compared to a similar vehicle having instead of the nontransparent element a transparent glass window that provides the same FOV to the outside environment as provided by the 3D display device, and provides the same safety level, (iii) better aerodynamic shape and lower drag for the vehicle, which results in an improved energy consumption, and (iv) improved privacy for the occupant as a result of not enabling an unauthorized person standing nearby the vehicle to see the occupant directly.","The term “real-depth VST window (VSTW)” is defined herein as an imaging display that shows a 3D image of an outside environment located beyond a wall that interrupts the occupant's unaided view of the outside environment.","The real-depth VSTW has the following characteristics: (i) the 3D image corresponds to a FOV to the outside environment beyond the wall, as would have essentially been seen by the occupant had the wall been removed; (ii) the outside environment is captured by a camera, and the rendering of the 3D image is based on images taken by the camera; and (iii) while looking via the imaging display, the occupant's point of gaze (where one is looking) is most of the time beyond the wall that interrupts the occupant's unaided view of the outside environment.","A possible test to determine whether “(i) the 3D image corresponds to a FOV to the outside environment beyond the wall, as would have essentially been seen by the occupant had the wall been removed” is whether an imaginary user standing beyond the wall, watching both the real-depth VSTW and the outside environment, would recognize that at least 20% of the contours of objects in the 3D image correspond to the contours of the objects seen on the outside environment.","Differences between the colors of the corresponding objects in the 3D image and the outside environment usually do not affect the criterion of the 20% corresponding contours, as long as the color difference does not affect the perception of the type of object.","For example, different skin colors to corresponding people in the 3D image and the outside environment do not violate the criterion of the 20% corresponding contours.","As another example, differences in the weight and/or height of corresponding objects in the 3D image and the outside environment do not violate the criterion of the 20% corresponding contours as long as the imaginary user understands that the objects correspond to the same person.","Sentences such as “from the FOV of the occupant” are to be interpreted as no more than 20 degrees angular deviation from the field of view of the occupant to the outside environment.","Zoom in/out does not affect the FOV as long as the average occupant would still recognize the rendered environment as the 3D VST.","For example, zoom in of up to ×4, which maintains no more than 20 degrees angular deviation from the FOV of the occupant to the outside environment, is still considered “from the FOV of the occupant”.","Reasonable lateral deviation essentially does not affect the FOV as long as the average occupant would still recognize the rendered environment as the 3D VST.","For example, displaying to the occupant the outside environment from the FOV of a camera located on the roof of the occupant's vehicle, is still considered as showing the outside environment from the occupant's FOV.","A possible test to determine whether “(ii) the outside environment is measured by a camera, and the images taken by the camera are used to render the 3D image” is whether the real-depth VSTW would display a different 3D VST when it does not receive the images taken by the camera.","For example, assuming the camera is a 3D video camera, and the 3D image is a manipulation of the images taken by the 3D video camera; then, when the real-depth VSTW does not receive the images, it cannot show the changes that are taking place in the outside environment.","As another example, assuming the 3D image is mainly rendered from cached data stored in a database, and the camera is used to provide the setup of objects that behave in an unknown way, such as trajectories of nearby vehicles on the road, or a gesture of a person walking beyond the wall; then, when the output of the camera is used to render the 3D image, the real-depth VSTW would represent the unknown trajectory of the nearby vehicles or the unknown gesture of the person, while when the output of the camera is not used to render the 3D image, the real-depth VSTW would not represent the unknown trajectory of the nearby vehicles or the unknown gesture of the person merely because the renderer does not have that data.","A possible test to determine whether “(iii) the occupant's point of gaze (where one is looking) is most of the time beyond the wall that interrupts the occupant's unaided view of the outside environment” includes the following steps: (a) use eye tracker to determine the point of gaze on a representative scenario, (b) measure the distance to the wall, and (c) determine whether the average gaze distance is longer than the distance to the wall.","Some aspects of this disclosure involve a system that utilizes window shading of a vehicle window in order to improve the quality of video viewed by an occupant of the vehicle who wears a head-mounted display (HMD).","In one embodiment, an autonomous on-road vehicle includes a system configured to enable an HMD to cooperate with a window light shading module.","This embodiment involves a light shading module, a camera, a processor, and the HMD.","The light shading module is integrated with a vehicle window and is configured to be in at least one of first and second states.","In the first state the Visible Light Transmittance (VLT) of the vehicle window is above 10% of ambient light entering through the window, in the second state the VLT of the vehicle window is below 50% of ambient light entering through the window, and the VLT of the vehicle window in the first state is higher than the VLT of the vehicle window in the second state.","The camera is fixed to the vehicle and configured to take video of the outside environment.","The processor is configured to generate, based on the video, a video see-through (VST) that represents the outside environment from a point of view of an occupant looking to the outside environment through at least a portion of the vehicle window.","The HMD comprises an optical see-through component and a display component; the HMD is configured to operate according to a first mode of operation when the occupant looks at the direction of the vehicle window and the light shading module is in the first state, and to operate according to a second mode of operation when the occupant looks at the direction of the vehicle window and the light shading module is in the second state.","Wherein the total intensity of the VST light, emitted by the display component and reaching the occupant's eyes, is higher in the second mode than in the first mode.","In one embodiment, a system configured to enable a head-mounted display (HMD) to cooperate with a window light shading module of an autonomous on-road vehicle includes at least the following elements: the HMD 62, a light shading module 61, a camera (such as camera 12), and a processor 18.FIG.","12 is a schematic illustration of at least some of the relationships between the system elements mentioned above.","The light shading module 61 is integrated with a vehicle window and is configured to be in at least one of first and second states.","Optionally, the light shading module 61 covers more than half of the front windshield in the second state.","In one embodiment, in the first state, the Visible Light Transmittance (VLT) of the vehicle window is above 10% of ambient light entering through the window, and in the second state, the VLT of the vehicle window is below 50% of ambient light entering through the window.","Additionally, the VLT of the vehicle window in the first state is higher than the VLT of the vehicle window in the second state.","In another embodiment, in the first state the VLT of the vehicle window is above 70% of ambient light entering through the window, and in the second state, the VLT of the vehicle window is below 30% of ambient light entering through the window.","Herein, “ambient light” in the context of a vehicle refers to visible light that is not controlled by the vehicle, such as light arriving from: the sun, lights of other vehicles, street/road lighting, and various reflections from elements such as windows.","In some embodiments, utilizing the light shading module 61 may improve the quality of images viewed via the HMD 62 when the light shading module 61 is in the second state.","Optionally, the perceived contrast of the optical see-through component is better when the light shading module is in the second state compared to when the light shading module 61 is in the first state.","Various types of light shading modules may be utilized in embodiments described herein.","In one embodiment, the light shading module 61 is a movable physical element configured to reduce the intensity of the ambient light entering into the vehicle compartment through the vehicle window.","Optionally, the light shading module is unfurled on the inside of the compartment in order to block at least 50% of the ambient light intensity.","Optionally, the light shading module is unfurled on the outside of the compartment in order to block at least 50% of the ambient light intensity.","FIG.","13a illustrates a first mode where the occupant sees the outside environment through the optical see-through component.","This figure illustrates the view that the occupant sees when looking outside through the window.","FIG.","13b illustrates a second mode where the occupant sees the outside environment through the VST.","In this example, the outside environment is a bit different, and there is also a virtual Superman floating near the tree.","In another embodiment, the light shading module 61 may be a curtain.","FIG.","14 illustrates a VST over a curtain.","FIG.","15 illustrates a light shading module that is unfurled on the inside of the compartment.","FIG.","16 illustrates a light shading module that is unfurled on the outside of the compartment.","And in yet another embodiment, the vehicle window is made of a material that is able to serve as the light shading module 61 by changing its transparency properties.","The camera is fixed to the vehicle, and configured to take video of the outside environment.","For example, the camera may be based on at least one of the following sensors: a CCD sensor, a CMOS sensor, a near infrared (NIR) sensor, an infrared sensor (IR), and a device based on active illumination such as a LiDAR.","The processor is configured to generate, based on the video, a video see-through (VST 19) that represents the outside environment from a point of view of an occupant looking to the outside environment through at least a portion of the vehicle window.","Optionally, the processor is further configured not to generate the VST 19 when the HMD 62 operates in the first mode.","The HMD 62 comprises an optical see-through component and a display component.","Optionally, the HMD 62 is configured to operate according to a first mode of operation when the occupant looks at the direction of the vehicle window and the light shading module 61 is in the first state, and to operate according to a second mode of operation when the occupant looks at the direction of the vehicle window and the light shading module 61 is in the second state.","The total intensity of the VST light, emitted by the display component and reaching the occupant's eyes, is higher in the second mode than in the first mode.","In one embodiment, in the first mode, intensity of light that reaches the occupant's eyes via the optical see-through component is higher than intensity of light from the VST that is emitted by the display component and reaches the occupant's eyes.","And in the second mode, the intensity of light from the environment that reaches the occupant's eyes via the optical see-through component is lower than the intensity of light from the VST that is emitted by the display component and reaches the occupant's eyes.","In one example, the total intensity of VST light, emitted by the display component and reaching the occupant's eyes, is at least 50% higher in the second mode than in the first mode.","In some embodiments, the display component may be based on a digital display that produces the virtual image (such as in Oculus rift), direct retina illumination (such as in Magic Leap), or other methods that are capable of producing the virtual image.","In one embodiment, the system described above optionally includes an occupant tracking module configured to calculate the point of view of the occupant based on measurements of a sensor.","Optionally, the occupant tracking module is the HMD tracking module 27.Optionally, in this embodiment, the processor is further configured to render the VST based on data received from the occupant tracking module.","Optionally, the display is a three dimensional (3D) display configured to show the occupant the VST, such that point of gaze of the occupant, while looking via the 3D display device, is most of the time beyond the location of the light shading module 61.In some embodiments, an occupant of a vehicle may have the opportunity to view video see-through (VST), which is video generated based on video of the environment outside the vehicle.","VST can often replace the need to look out of a window (if the vehicle has windows).","Some examples of scenarios in which VST may be available in a vehicle include a windowless vehicle, a vehicle with shaded windows having VLT below 30%, and/or when the occupant wears a VR headset.","While traveling in such a vehicle, the occupant may benefit from gaining a view to the outside environment when an unexpected driving event occurs.","By being made aware of the event, the occupant is less likely to be surprised, disturbed, and/or distressed by the event.","While traveling in a vehicle, an occupant of the vehicle may not always be aware of the environment outside and/or of what actions the vehicle is about to take (e.g., breaking, turning, or hitting a speedbump).","Thus, if such an event occurs without the occupant being aware that it is about to happen, this may cause the occupant to be surprised, disturbed, distressed, and even physically thrown off balance (in a case where the event involves a significant change in the balance of the physical forces on the occupant).","This type of event is typically referred to herein as a Sudden Decrease in Ride Smoothness (SDRS) event.","Some examples of SDRS events include at least one of the following events: hitting a speed bump, driving over a pothole, climbing on the curb, making a sharp turn, a hard breaking, an unusual acceleration (e.g., 0-100 km/h in less than 6 seconds), and starting to drive after a full stop.","In some embodiments, an SDRS event takes place at least 2 minutes after starting to travel and it is not directly related to the act of the starting to travel.","Additionally, the SDRS event takes place at least 2 minutes before arriving to the destination and is not directly related to the act of arriving at the destination.","In one example, a sentence such as “an SDRS event is imminent” refers to an SDRS event that is: (i) related to traveling in the vehicle, and (ii) expected to happen in less than 30 seconds, less than 20 seconds, less than 10 seconds, or less than 5 seconds.","In another example, a sentence such as “an SDRS event is imminent” may refer to an event that starts at that instant, or is about to start within less than one second.","The following is a description of an embodiment of a video system that may be used to increase awareness of an occupant of a vehicle regarding an imminent SDRS.","In one embodiment, a video system for an autonomous on-road vehicle includes at least autonomous-driving control system 65, a camera (such as camera 12), a processor (such as processor 18), and video module 66.FIG.","17 is a schematic illustration of at least some of the relationships between the system elements mentioned above.","The autonomous-driving control system 65 is configured to generate, based on trajectory of the vehicle and information about the road, an indication indicative of whether a Sudden Decrease in Ride Smoothness (SDRS) event is imminent.","Optionally, the autonomous-driving control system 65 receives at least some of the information about the road from at least one of the following sources: sensors mounted to the vehicle, sensors mounted to nearby vehicles, an autonomous-driving control system 65 used to drive a nearby vehicle, and a database comprising descriptions of obstacles in the road that are expected to cause intense movement of the vehicle.","In one example, the database comprising the descriptions of the obstacles includes one or more of the following types of data: locations of speed bumps, locations of potholes, locations of stop signs, and locations of sharp turns in the road.","In one embodiment, the autonomous-driving control system 65 is configured to generate the indication indicative of whether an SDRS event is imminent based on at least one of the following configurations: (i) the autonomous-driving control system 65 receives images of the road from a camera, and calculates the indication based on the vehicle trajectory and image analysis of the images, (ii) the autonomous-driving control system 65 receives from a radar reflections of electromagnetic waves from the road, and calculates the indication based on the vehicle trajectory and signal processing of the reflections, and (iii) the autonomous-driving control system 65 receives a notification from a detailed road map, and calculates the indication based on the vehicle trajectory and the notification.","The camera, which is mounted to the vehicle, is configured to take video of the environment outside the vehicle.","Optionally, the data captured by the camera comprises 3D data.","The processor is configured to generate a video see-through (VST) based on the video taken by the camera.","The video module 66 is configured to select a first mode of presentation, in which a video-unrelated-to-the-VST (VUR) is presented on the foveal vision region of the occupant, at eye level, responsive to the indication not indicating that an SDRS event is imminent.","The video module 66 is further configured to select a second mode of presentation, in which the VST is presented on the foveal vision region of the occupant, at eye level, responsive to the indication indicating that an SDRS event is imminent.","Optionally, the VST captures more than 50% of the foveal vision region of the occupant in the second mode of presentation.","In some embodiments, presenting video on the foveal vision region comprises presenting images with at least 50% transparency.","Herein, “foveal vision” refers to an angle of about 5° of the sharpest field of vision.","In one embodiment, in the first mode of presentation, the VUR is presented on the foveal vision region of the occupant with opacity A, and the VST is presented on the foveal vision region of the occupant with opacity B, where A>B>0.Optionally, a normalized opacity parameter takes a value from 0.0 to 1.0, and the lower the value the more transparent the video is.","In this embodiment, in the second mode of presentation, the VUR is presented on the foveal vision region of the occupant with opacity A′, and the VST is presented on the foveal vision region of the occupant with opacity B′, where B′>B and B′>A′.","In optional embodiments, one or more of the following values may be true: A′>0, B=0, and A′=0.Herein, “partially transparent” refers to opacity below one and above zero.","Having the VST presented when an SDRS event is imminent can make the occupant be aware and prepared for the SDRS event.","Thus, the occupant is less likely to be startled, distressed, and/or physically thrown off balance by the SDRS event.","In one example, the SDRS event involves hitting a speedbump, while the occupant views a movie.","About 5 seconds prior to hitting the speedbump, a partially transparent window displaying VST in which the speedbump is highlighted (e.g., flashing red) is presented on the foveal vision region of the occupant for a couple seconds (e.g., by being presented in the center of the movie).","This way upon hitting the speedbump, the occupant is not startled by the event.","In another example, the autonomous-driving control system 65 determines that a “hard breaking” is required, e.g., in order to avoid collision with a vehicle ahead that slowed unexpectedly.","In this example, the occupant may be working on a virtual desktop, and within 100 milliseconds of when the determination is made that the vehicle is about to rapidly deaccelerate (a “hard breaking”), the VST depicting the rear of the vehicle ahead is displayed in the center of the virtual desktop.","This way the occupant is immediately made aware of why the vehicle is breaking and this notification may prompt the occupant to seek a more appropriate posture for the breaking.","Some illustrations of utilization of the different modes of operation are given in the following figures.","FIG.","18a illustrates presenting VUR responsive to not receiving from the autonomous-driving control system 65 an indication that an SDRS event is imminent.","This figure has two parts, the left part shows the vehicle driving over a clean road, and the right part shows the VUR.","FIG.","18b illustrates presenting VST responsive to receiving from the autonomous-driving control system 65 an indication that an SDRS event is imminent.","The figure has two parts, the left part shows the vehicle about to drive over a pothole, and the right part shows a small window showing the pothole over the VUR (optionally to warn the occupant).","FIG.","18c illustrates presenting VST responsive to receiving from the autonomous-driving control system 65 an indication that an SDRS event is imminent.","The figure has two parts, the left part shows the vehicle about to enter a sharp turn, and on the right part shows a small window showing the sharp turn over the VUR (optionally to warn the occupant).","Traditional vehicles typically have a front windshield that offers occupants of the vehicle a frontal view of the outside environment.","However, in some embodiments, this frontal view may be provided using the VST.","For example, in one embodiment, the vehicle includes a nontransparent element, which is coupled to the vehicle, and obstructs at least 30 degrees out of the frontal horizontal unaided FOV to the outside environment of an occupant at eye level.","In one example of a standard vehicle, such as Toyota Camry model 2015, the frontal horizontal unaided FOV extends from the left door through the windshield to the right door.","The use of the nontransparent element improves the safety of the occupant during a collision compared to a similar vehicle having the same total weight and comprising a transparent glass window instead of the nontransparent element.","The nontransparent element may be coupled to the vehicle in various configurations, in embodiments described herein.","In one embodiment, the nontransparent element is fixed to the vehicle at an angle, relative to the occupant, that is covered by the field of view of the VST, and the nontransparent element features visible light transmittance (VLT) below 10% of ambient light.","Various types of displays may be utilized to present the occupant with video (e.g., the VST and/or the VUR).","In one embodiment, the video is presented to the occupant on a screen coupled to the vehicle compartment.","In one example, the screen coupled to the vehicle compartment utilizes parallax barrier technology.","A parallax barrier is a device located in front of an image source, such as a liquid crystal display, to allow it to show a stereoscopic image or multiscopic image without the need for the viewer to wear 3D glasses.","The parallax barrier includes a layer of material with a series of precision slits, allowing each eye to see a different set of pixels, thus creating a sense of depth through parallax.","In another embodiment, the occupant wears a head-mounted display (HMD), and the HMD is used to present the video to the occupant.","Optionally, the HMD is a VR headset, and as a result of presenting the VST, the occupant does not need to remove the VR headset in order to see the cause of the SDRS event.","In some embodiments, the video module 66 may be selective regarding indications of which SRDS events may prompt it to operate in the second mode of operation.","For example, if the occupant is engaged in a game, the video module 66 may refrain from presenting the VST in the foveal vision region if the vehicle is about to make a sharp turn.","However, it may optionally still present the VST in the foveal vision region if the SDRS event involves something that may be more forcefully felt by the occupant, such as extreme evasive maneuvering performed to avoid a collision.","In some embodiments, the video module 66 may determine whether to show a VST responsive to an SRDS event (in the second mode of operation) based on the level of concentration of the occupant.","For example, if the occupant is deeply engaged in a certain activity (e.g., in work or playing a game) above a threshold, the video module 66 may refrain from operating in the second mode for certain SDRS events that would cause the video module 66 to operate in the second mode were the occupant engaged in the certain activity below the threshold.","In one example, the engagement level may be based on the occupant's level of concentration, as measured by a wearable sensor (such as an EEG headset or a smartwatch) or a sensor fixed to the compartment (such as an eye tracker, a thermal camera, or a movement sensor embedded in the seat).","Presenting an occupant of a vehicle with video see-through (VST) of the outside environment from a point of view of the occupant can help the occupant be prepared for various events that may be considered to cause a Sudden Decrease in Ride Smoothness (SDRS events).","Some examples of SDRS events include the following events: hitting a speed bump, driving over a pothole, climbing on the curb, making a sharp turn, a hard breaking, an unusual acceleration (e.g., 0-100 km/h in less than 6 seconds), and starting to drive after a full stop.","In order for the occupant to become aware of an imminent SDRS event, the VST needs to be presented in an attention-grabbing way.","For example, when an SDRS event is imminent, the VST that describes the environment is brought to the center of the occupant's attention by displaying it at eye level and/or increasing the size of the VST (compared to other times when an SDRS event is not imminent).","The following is a description of an embodiment of a video system that may be used to increase awareness of an occupant of a vehicle regarding an imminent SDRS by making the VST more prominent for an imminent SDRS.","In one embodiment, a video system for an autonomous on-road vehicle includes at least the autonomous-driving control system 65, a camera, and a processor.","In this embodiment, the occupant is engaged, at least part of the time, in entertainment- or work-related activities, which involve presentation of video-unrelated-to-the-VST (VUR) to the occupant, for example, on a screen coupled to the compartment of the vehicle or a HMD worn by the occupant.","Some examples of such content (common in the year 2016) include cinema movies, broadcast TV shows, standard web browsers, and Microsoft Office 2016 applications (such as Word, Excel and PowerPoint).","The camera, which is mounted to the vehicle, is configured to take video of the environment outside the vehicle.","The processor is configured to generate, based on the video taken by the camera, a video see-through (VST) of outside environment from a point of view of an occupant of the vehicle.","Optionally, the occupant is in a front seat of the vehicle (such that no other occupant in the vehicle is positioned ahead of the occupant).","In some embodiments, the processor is configured to present video, which may include VUR and/or VST, to the occupant using different presentation modes, depending on whether an SDRS event is imminent.","For example, the video may be presented according to first or second modes, depending on whether an SDRS event is imminent.","Optionally, the VST captures in the video according to the first mode a diagonal FOV of at least 3°, 5°, or 10° of the occupant's FOV.","Optionally, the VST is not presented in the foveal vision region of the occupant in the video according to the first mode, while the VST is presented in the foveal vision region of the occupant in the video according to the second mode.","In one embodiment, responsive to an indication that is not indicative of an imminent SDRS event (generated by the autonomous-driving control system 65), the processor is configured to provide the occupant video according to the first mode.","In the video according to the first mode, the occupant is presented with video that comprises a video-unrelated-to-the-VST (VUR) at eye level in the direction of forward traveling.","Additionally, the video may comprise a video see-through (VST) of outside environment that is not presented at eye level in the direction of forward traveling.","Receiving an indication indicative that an SDRS event is imminent may change the way video is presented to the occupant.","Optionally, this change is made without receiving a command to do so from the occupant.","In one embodiment, responsive to the indication indicating that an SDRS event is imminent, the processor is configured to provide video to the occupant video according to the second mode.","In the video according to the second mode, the occupant is presented with video that comprises the VST, presented at eye level in the direction of forward traveling.","Optionally, if the video according to the first mode includes VST, then the size of the VST window in the video according to the second mode is larger by at least 25% relative to the size of the VST window in the video according to the first mode.","Optionally, the video according to the second mode includes presenting the VUR in the background (e.g., the VST is overlaid above the VUR).","Optionally, while providing the video according to the second mode, responsive to an updated indication that does not indicate that an SDRS event is imminent, the processor is further configured to switch back to provide the video according to the first mode to the occupant.","The following figures illustrate various ways in which the videos according to the first and second modes may be utilized.","FIG.","19a illustrates presenting a VUR, which is a movie showing a person skiing, responsive to not receiving from the autonomous-driving control system 65 an indication that an SDRS event is imminent.","This figure has two parts, the left part shows the vehicle driving over a clean road, and the right part shows the VUR with a small VST on the right.","FIG.","19b illustrates presenting a VST responsive to receiving from the autonomous-driving control system 65 an indication that an SDRS event is imminent.","This figure has two parts, the left part shows the vehicle about to drive over a speed bump, and the right part shows the VUR but now with a big VST on the right.","In this example, the big VST captures about half of the VUR and shows the speed bump.","FIG.","19c illustrates presenting a partially transparent VST responsive to receiving from the autonomous-driving control system 65 an indication that an SDRS event is imminent.","Here, the big VST (that captures about half of the VUR and shows the speed bump) is presented as partially transparent layer over the VUR in order to show the occupant both the VUR and the VST.","In one embodiment, presenting to the occupant video according to the second mode involves presenting the VUR behind the VST, and the size and location of the VUR in the video according to the second mode is essentially the same as the size and location of the VUR in the video according to the first mode.","Optionally, this means that there is a difference of less than 10% in the size and location of the VURs in the videos according to the first and second modes.","In another embodiment, the VUR is presented in a diagonal FOV of at least 10 degrees, and is not based on the video taken by the camera.","In some embodiments, the VUR may be unrelated to the purpose of the traveling in the vehicle.","For example, the VUR may include videos related to the following activities: watching cinema movies, watching TV shows, checking personal emails, playing entertainment games, and surfing in social networks.","In some embodiments, the occupant's field of view (FOV) to the outside environment is obstructed by a nontransparent element, and the VST represents at least a portion of the obstructed FOV.","Optionally, the occupant uses a VR headset and the obstruction is due to a nontransparent element belonging to the VR headset.","Additionally or alternatively, the obstruction may be due to the vehicle's compartment; in this case the nontransparent element may be an SAEDP, a safety beam, and/or a crumple zone at eye level, which obstruct at least 30 degrees out of the frontal horizontal unaided FOV to the outside environment of the occupant at eye level.","When traveling in a vehicle, an occupant of the vehicle may not always be viewing the outside environment.","For example, the occupant may be engaged in work- or entertainment-related activities.","Additionally, in some vehicles, the occupant may not have a good view of the outside environment most of the time, or even all of the time.","For example, the vehicle may have very few (or no) windows, or the vehicle may have a shading mechanism that reduces the light from the outside.","However, there are times when the occupant should be made aware of the outside environment, even though the occupant may not be actively driving the vehicle.","For example, the occupant may be made aware of the outside environment in order to make the occupant prepared for an event that causes a Sudden Decrease in Ride Smoothness (an SDRS event).","Some examples of SDRS events include the following events: hitting a speed bump, driving over a pothole, climbing on the curb, making a sharp turn, a hard breaking, an unusual acceleration (e.g., 0-100 km/h in less than 6 seconds), and starting to drive after a full stop.","In order for the occupant to become aware of an imminent SDRS event, in some embodiments that involve a vehicle that has a shading module that controls how much ambient light is let in, when an SDRS event is imminent the vehicle may increase the amount of light that enters via a window.","This additional light can give an occupant a better view of the outside environment, which can make the occupant aware and better prepared for the SDRS.","The following is a description of an embodiment of a system that may be used to increase awareness of an occupant of a vehicle regarding an imminent SDRS by enabling more ambient light to enter a vehicle via a window.","In one embodiment, a shading system for a window of an autonomous on-road vehicle includes at least the autonomous-driving control system 65, a shading module, and a processor.","FIG.","20a illustrates a smart glass shading module that operates according to an indication that an SDRS event is not imminent.","This figure has two parts, the left part shows the vehicle driving over a clean road, and the right part shows that the smart glass window blocks most of the ambient light (illustrated in the figure by the tree outside that is invisible to the occupant).","FIG.","20b illustrates the smart glass shading module that operates according to an indication that an SDRS event is imminent.","This figure has two parts, the left part shows the vehicle about to drive over a pothole, and the right part shows that the smart glass window does not block the ambient light (illustrated in the figure by the tree outside that is visible to the occupant).","The shading module is configured to control the amount of ambient light that enters the vehicle via the window.","Optionally, the window is a front-facing window (e.g., a windshield).","Optionally, the window is a side-facing window.","There are various types of shading modules that may be utilized in different embodiments.","In one embodiment, the shading module comprises a curtain.","Optionally, the curtain covers most of the area of the window.","Optionally, the curtain may open and close with the aid of an electromechanical device, such as a motor, based on commands issued by the processor.","In another embodiment, the shading module is a movable physical element configured to reduce the intensity of the ambient light entering through the vehicle window into the vehicle compartment.","For example, the shading module may include various forms of blinds, a shutter, or a sliding element.","Optionally, the shading module may be unfurled on the inside of the vehicle compartment in order to block more than 70% of the ambient light intensity.","Optionally, the shading module may be unfurled on the outside of the vehicle compartment in order to block more than 70% of the ambient light intensity.","In yet another embodiment, the shading module comprises a smart glass able to change its light transmission level.","Optionally, the smart glass is a vehicle window smart glass that comprises suspended particle devices (SPDs) film.","Smart glass window may also be known as a switchable glass, a smart window, and/or a switchable window.","Smart glass is glass or glazing whose light transmission properties are altered when voltage, current, light or heat is applied.","Examples of electrically switchable smart glass include: suspended particle devices (SPDs), electrochromic devices, transition-metal hydride electrochromics devices, modified porous nano-crystalline films, polymer dispersed liquid crystal devices, micro-blinds, and thin coating of nanocrystals embedded in glass.","Examples of non-electrical smart glass include: mechanical smart windows, Vistamatic®, and Sunvalve.","The processor is configured to command the shading module to operate in different modes based on indications generated by the autonomous-driving control system 65.In some embodiments, the processor is configured to command the shading module to operate in different modes that allow different amounts of the ambient light to enter the vehicle via the window, depending on whether an SDRS event is imminent.","For example, shading module may operate in first or second modes, depending on whether an SDRS event is imminent.","Optionally, in the first mode the shading module blocks more of the ambient light entering through the vehicle window than in the second mode.","Optionally, the increased ambient light in the second mode can help make the occupant more aware of the outside environment, which can enable the occupant to prepare for the SDRS event.","In one embodiment, responsive to an indication that no SDRS event is imminent, the processor is configured to command a shading module to operate in a first mode in which the shading module blocks more than 30% of ambient light entering through a window of the vehicle.","Receiving an indication indicative that an SDRS event is imminent may change the amount of ambient light that enters the vehicle via the window.","Optionally, this change is made without receiving a command to do so from the occupant.","In one embodiment, responsive to an indication that an SDRS event is imminent, the processor is configured to command the shading module to operate in the second mode in which the shading module blocks less than 90% of the ambient light entering through the vehicle window.","Some aspects of this disclosure include a system that can show an occupant of a vehicle and Object Of Interest (OOI) in the outside environment, which the occupant would otherwise miss (e.g., due to being engaged in work- or entertainment-related activities and/or having no direct view of the outside environment).","In one embodiment, a system configured to identify an Object Of Interest (OOI) in the outside environment, and to present to an occupant of an autonomous on-road vehicle a video see-through (VST) that comprises the OOI, includes at least a camera (such as camera 12), a processor (such as processor 18), and a video module (such as video module 66).","Different types of things may be considered an OOI in different embodiments.","In one embodiment, the OOI is selected from a set comprising: types of vehicles, types of scenery, and types of people.","Optionally, the system may include a user interface configured to present a menu that enables the occupant to select the types of OOI, which when identified, will be presented in the second mode of presentation.","In one example, an OOI may be any type of high-end vehicle (e.g., a Porsche).","In another example, an OOI may include an ocean view.","The camera, which is mounted to the vehicle, is configured to take video of the environment outside the vehicle.","Optionally, the data captured by the camera comprises 3D data.","The processor is configured to generate, based on the video taken by the camera, a video see-through (VST) of outside environment from a point of view of an occupant of the vehicle.","Optionally, the occupant is in a front seat of the vehicle (such that no other occupant in the vehicle is positioned ahead of the occupant).","The video module is configured to present, to the occupant, video that captures diagonal field of view (FOV) of at least 10 degrees, at eye level.","Optionally, the video module is further configured to select a mode of operation based on whether an indication is received that is indicative of whether video taken by the camera include the OOI.","Optionally, changing a mode of operation is done without an expressed command at that time by the occupant.","In one embodiment, when not receiving an indication that the images includes the OOI, the video module is configured to select a first mode of presentation, in which a video-unrelated-to-the-VST (VUR) is presented on the foveal vision region of the occupant.","And responsive to receiving the indication that the images include the OOI, the video module is further configured to select a second mode of presentation, in which the VST is presented on the foveal vision region of the occupant.","There are various ways in which an indication of the OOI may be generated in different embodiments.","In one embodiment, the system includes an image processing module configured to identify the OOI in the VST and to generate the indication.","Various image processing techniques and/or image identification methods known in the art may be utilized by the image processing module for this task.","In another embodiment, the system may include the autonomous-driving control system 65 configured to utilize a positioning system, such as GPS coordinates, to identify that the vehicle reached the OOI and to generate the indication.","Optionally, the occupant may define which places may be OOIs and/or what types of locations are to be considered OOIs (e.g., historical monuments, nice scenery, etc.).","In still another embodiment, the system may include a crowd-based module configured to identify the OOI based on feedback received from many different occupants who watched VSTs comprising the OOI.","Optionally, this feedback may be derived based on indications of how other occupants felt about the VST (when it depicted certain content corresponding to OOIs).","For example, points of interest may be determined according to affective crowd data, determine based on how other occupants felt about what they saw, and optionally find places where the crowd affective response was positive (e.g., blooming of flowers, etc.).","Optionally, some occupants who watched the video related to the unhindered FOV for long periods (or have a physical window) may be monitored to see when an interesting view is encountered.","Points of interest may involve items identified in the exterior environment using image analysis, including presenting the VST when one or more of the following happens: passing a fancy vehicle, passing someone the occupant knows, passing a vehicle accident, passing a police officer, having a sunset view, and passing an animal the occupant is interested in.","In one embodiment, the system may receive an indication that the occupant is feeling at least one of nauseous and claustrophobic, and consequently present the VST in order to help the occupant to confront the feeling.","For example, when there is a serious spike (e.g., increase in heart-rate and sweating), then the system may present the VST automatically.","The system may also present a “normal” interior to the occupant (e.g., natural lighting settings).","Optionally, when digital content is consumed (e.g., a game or a movie), the system may check whether the affective spike (e.g., increased excitement) is due to the content or due to the experience of being in the vehicle with AR or VR.","If it is the former case, then the system might not present the VST.","Some aspects of this disclosure involve an autonomous on-road vehicle that includes a nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) that is coupled to the compartment of the vehicle and is located, during normal driving, at eye level in front of an occupant who sits in a front seat of the vehicle.","Additionally, the vehicle includes a stiff element that is configured to support the SAEDP and to resist deformation during collision in order to reduce compartment intrusion.","The stiff element is located, during normal driving, at eye level between the SAEDP and the outside environment.","Thus, the combination of the SAEDP and the stiff element offers the occupant an increased level of protection, e.g., in the case of a collision, compared to a vehicle in which a traditional window is in place at eye level in the front of the vehicle.","However, due to it being nontransparent, placing the SAEDP at eye level may obstruct the occupant's view to the outside.","Thus, in order to offer the occupant such a view, in some embodiments, the vehicle also includes a camera configured to take video of the outside environment in front of the occupant, and a computer configured to generate, based on the video, a representation of the outside environment in front of the occupant at eye level.","This representation may be provided to the occupant using various types of displays.","One non-limiting advantage of the vehicle described above is that it increases the safety of the occupant in the case of a collision, without prohibiting the occupant from obtaining a view of the outside environment.","In one embodiment, an autonomous on-road vehicle includes a compartment, which one or more occupants may occupy while traveling in the vehicle (e.g., by sitting in seats).","Coupled to the front of the compartment is a Shock-Absorbing Energy Dissipation Padding (SAEDP) and a stiff element that supports the SAEDP.","Optionally, the SAEDP is nontransparent.","The stiff element is located, during normal driving, at eye level between the SAEDP and the outside environment.","Additionally, the vehicle includes a camera (e.g., camera 142 or structure 147 that comprises multiple cameras), which is configured to take video of the outside environment in front of the occupant, and a computer (e.g., computer 143) that is configured to generate, based on the video, a representation of the outside environment in front of the occupant at eye level.","Optionally, the camera, and/or each of the cameras in the structure 147, may be based on at least one of the following sensors: a CCD sensor, a CMOS sensor, a near infrared (NIR) sensor, an infrared sensor (IR), and a device based on active illumination such as a LiDAR.","Optionally, when the camera comprises multiple cameras, the multiple cameras are directed to multiple directions around the vehicle, and the multiple cameras support generating multiple representations of the outside environment from different points of view.","It is to be noted that in some embodiments, the SAEDP may be fixed at its location both in normal driving and in times that are not considered to correspond to normal driving, while in other embodiments, the SAEDP may change its location during at least some of the times that do not correspond to normal driving.","The SAEDP is coupled to the compartment in such a way that it is located, during normal driving, at eye level in front of an occupant who sits in a front seat of the vehicle.","Different types of SAEDPs may be utilized in different embodiments.","In one embodiment, the SAEDP comprises a passive material that is less stiff than a standard automotive glass window.","The passive material is configured to protect the occupant's head against hitting the inner side of the vehicle compartment during a collision.","Optionally, the passive material has thickness greater than at least one of the following thicknesses: 1 cm, 2 cm, 5 cm, 10 cm, 15 cm, and 20 cm.","Optionally, the thickness of the passive material may refer to the average thickness of the SAEDP across the portion of the SAEDP at eye level.","Alternatively, the thickness may refer to the maximal thickness at some position of the SAEDP (which is at least one of the values mentioned above).","In another embodiment, the SAEDP comprises a pneumatic pad that is configured to inflate in order to protect the occupant's head against hitting the inner side of the vehicle compartment during collision.","In some examples, the pneumatic pads may be formed from an elastomeric material providing chambers containing air or another gas.","Optionally, the chambers are retained in compressed deflated condition until being inflated by the admission of gas pressure controlled by the vehicle's autonomous-driving control system that is responsible to estimate the probability and severity of an imminent collision.","Additionally or alternatively, the chambers may be provided with restricted passages limiting the flow out from the chambers to provide shock-absorbing energy dissipation to reduce the rebound effect.","U.S. Pat.","No.","5,382,051 discloses examples for pneumatic pads that can be used with some of the embodiments.","In yet another embodiment, the SAEDP comprises an automotive airbag, which is configured to protect the occupant's head against hitting the inner side of the vehicle compartment during collision.","In one example, during normal driving, the airbag is in a stowed state.","The airbag is coupled to an inflator configured to inflate the airbag with gas to an inflated state, upon receiving an indication indicative of a probability of an impact of the vehicle exceeding a threshold.","In this example, the airbag is located, when in the stowed state, at eye level in front of the occupant.","In some embodiments, the compartment may include a door, and the SAEDP is physically coupled to the door from the inside, such that the SAEDP moves with the door as the door opens and/or closes.","In some embodiments, the vehicle may include a second SAEDP coupled to the outer front of the vehicle to minimize damage to a pedestrian during a pedestrian-vehicle collision.","In one embodiment, the stiff element that supports the SAEDP is nontransparent.","In another embodiment, the stiff element may be automotive laminated glass or automotive tempered glass.","Optionally, the structure of the vehicle comprises a crumple zone located at eye level between the stiff element and the outside environment.","The representation of the outside environment is intended to provide the occupant with some details describing the outside environment.","In some embodiments, the representation of the outside environment is generated from the point of view of the occupant, and it represents how a view of the outside environment would look like to the occupant, had there been a transparent window at eye level instead of the SAEDP and/or the stiff element.","Optionally, a display is utilized to present the representation to the occupant.","Various types of displays may be utilized in different embodiments to present the representation of the outside environment to the occupant.","In one embodiment, the display is comprised in an HMD, and the vehicle further comprises a communication system configured to transmit the representation to the HMD.","For example, the HMD may be a virtual reality system, an augmented reality system, or a mixed-reality system.","In one embodiment, the display is supported by at least one of the SAEDP and the stiff element.","For example, the display is physically coupled to the SAEDP and/or the stiff element.","Optionally, the display is a flexible display.","For example, the flexible display may be based on at least one of the following technologies and their variants: OLED, organic thin film transistors (OTFT), electronic paper (e-paper), rollable display, and flexible AMOLED.","In one example, the display is flexible enough such that it does not degrade the performance of the SAEDP by more than 20% during a collision.","In one example, the performance of the SAEDP is measured by hitting a crash test dummy head against the SAEDP and measuring the head's deceleration using sensors embedded in the head.","FIG.","21a, FIG.","21b, and FIG.","22 illustrate various embodiments of the vehicle described above.","Each of the illustrated vehicles comprises a cross-section view of the vehicles, where each includes a compartment 145 for a single occupant (in FIG.","21b) or more (in FIG.","21a and FIG.","22).","In the figures, much of the compartment is covered with the SAEDP 140, which is nontransparent and comprises a soft passive material (cushiony in its nature).","Supporting the SAEDP 140 is a stiff element 141, which in the illustrations comprises portions of the exterior (hull) of the vehicle which may optionally be made of one or more of the following materials: fiber-reinforced polymer, carbon fiber reinforced polymer, steel, and aluminum.","The vehicles also include a camera (such as camera 142 and/or structure 147 that houses multiple cameras), which is positioned to capture a front view of the outside environment of the vehicle.","Additionally, the vehicles include a computer 143, which may be positioned in various locations in the vehicle.","In some embodiments, the computer may be comprised of multiple processors and/or graphics processors that may be located at various locations in the vehicle.","The figures illustrate various types of displays that may be utilized to present the occupant with the representation of the outside environment generated by the computer 143 based on the video taken by the camera 142.In FIG.","21a the representation is presented via an HMD 144, which may be, for example, a virtual reality HMD.","In FIG.","21b the representation is presented via an HMD 146, which may be, for example, a mixed-reality headset.","And in FIG.","22 the representation may be provided via one or more of the displays 150, which are coupled to the compartment.","It is to be noted that in the figures described above not all of the described elements appear in each figure.","The figures also illustrate various structural alternatives that may be implemented in different embodiments described herein.","For example, FIG.","21a illustrates a vehicle that includes window 148, which may optionally be an automotive tempered glass window, located in a location in which the head of a belted occupant is not expected to hit during collision.","FIG.","21b illustrates a vehicle that includes crumple zone 149, which is located at the front of the vehicle at eye level.","The figure also illustrates the structure 147 that houses multiple cameras directed to multiple directions around the vehicle.","In some embodiments, the representation of the outside environment may be manipulated in order to improve how the outside environment looks to the occupant.","Optionally, this may be done utilizing the computer.","In one example, manipulating the representation includes at least one of the following manipulations: converting captured video of an overcast day to video of a sunny day by preserving main items in the captured video (such as vehicles and buildings) and applying effects of a sunny day, converting unpleasant environment to a nice one, converting standard vehicles to futuristic or old fashion vehicles, and adding fans standing outside and waiving to the occupant.","In one embodiment, the manipulation maintains the main items in the environment, such that the occupant would still know from the manipulated representation where he/she is traveling.","In another embodiment, the manipulated representation maintains the main objects in the video of the outside environment, such that the main objects presented in the manipulated video essentially match the main objects that would have been seen without the manipulation.","In some embodiments, the vehicle compartment may include an automotive laminated glass window or automotive tempered glass window located in a location where the head of a belted occupant is not expected to hit as a result of collision while traveling in velocity of less than 50 km/h, as illustrated by the dotted rectangle 148 in FIG.","21a.","In one embodiment, the structure of the vehicle is such that a crumple zone is located at eye level between the stiff element and the outside environment.","Various types of vehicles may benefit from utilization of the nontransparent SAEDP supported by the stiff element and in conjunction with the camera and computer, as described above.","The following are some examples of different characterizations of vehicles in different embodiments.","In one embodiment, the vehicle weighs less than 1,500 kg without batteries, and it is designed to carry up to five occupants.","In another embodiment, the vehicle weighs less than 1,000 kg without batteries, and it comprises an engine that is able to sustain continuously at most 80 horsepower.","In yet another embodiment, the vehicle weighs less than 1,000 kg and it is designed to carry up to two occupants.","In still another embodiment, the vehicle weighs less than 800 kg without batteries, and it comprises an engine that is able to sustain continuously at most 60 horsepower.","In yet another embodiment, the vehicle weighs less than 500 kg without batteries and it comprises an engine that is able to sustain continuously at most 40 horsepower.","And in still another embodiment, the vehicle weighs less than 400 kg without batteries and is designed to carry up to two occupants.","Some aspects of this disclosure involve an autonomous on-road vehicle that includes a nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) that is coupled to the compartment and is located, during normal driving, at eye level to the left of the occupant who sits in a front seat of the vehicle (in the left front seat when the vehicle has more than one front seat).","The SAEDP obstructs at least 30 degrees out of the horizontal unaided field of view (FOV) to the outside environment to the left of the occupant at eye level.","Additionally, the vehicle includes a stiff element that is configured to support the SAEDP and to resist deformation during collision in order to reduce compartment intrusion.","The stiff element is located, during normal driving, at eye level between the SAEDP and the outside environment.","Thus, the combination of the SAEDP and the stiff element offers the occupant an increased level of protection, e.g., in the case of a collision to the left side of the vehicle, compared to a vehicle in which a traditional window is in place at eye level on the left side of the vehicle.","However, due to it being nontransparent, placing the SAEDP at eye level may obstruct the occupant's view to the outside.","Thus, in order to offer the occupant such a view, in some embodiments, the vehicle also includes a camera configured to take video of the outside environment to the left of the occupant, and a computer, which is configured to generate, based on the video, a representation of the outside environment to the left of the occupant at eye level.","This representation may be provided to the occupant using various types of displays.","One non-limiting advantage of the vehicle described above is that it increases the safety of the occupant in the case of a side collision, without prohibiting the occupant from obtaining a side view of the outside environment.","In one embodiment, an autonomous on-road vehicle includes a compartment, which one or more occupants may occupy while traveling in the vehicle (e.g., by sitting in seats).","Coupled to the compartment is a Shock-Absorbing Energy Dissipation Padding (SAEDP) and a stiff element that supports the SAEDP.","Optionally, the SAEDP is nontransparent.","The SAEDP is located, during normal driving, at eye level to the left of the occupant who sits in a front seat of the vehicle.","The stiff element is located, during normal driving, at eye level between the SAEDP and the outside environment.","Optionally, the stiff element is nontransparent.","Optionally, the stiff element may be automotive laminated glass or automotive tempered glass.","The vehicle also includes a camera (such as camera 161) that is configured to take video of the outside environment to the left of the occupant, and a computer that is configured to generate, based on the video, a representation of the outside environment to the left of the occupant at eye level.","Optionally, the camera comprises multiple cameras directed to multiple directions around the vehicle, and the multiple cameras support generating multiple representations of the outside environment from different points of view.","FIG.","23 illustrates one embodiment of the autonomous on-road vehicle described above, which shows how an SAEDP protects the occupant during a collision.","In the figure, SAEDP 160 (which may comprise a passive material) is coupled to the stiff element 141.When another vehicle collides with the side of the vehicle, the occupants head strikes the soft SAEDP 160, instead of a glass window (which would be positioned there in many conventional vehicles).","The SAEDP is coupled to the compartment in such a way that it is located, during normal driving, at eye level to the left of the occupant who sits in a front seat of the vehicle.","Optionally, due to its location, the SAEDP obstructs at least 30 degrees out of the horizontal unaided field of view (FOV) to the outside environment to the left of the occupant at eye level.","Optionally, the SAEDP obstructs at least 45 degrees or at least 60 degrees out of the horizontal unaided FOV to the outside environment to the left of the occupant at eye level.","In one example of a standard vehicle, such as Toyota Camry model 2015, the frontal horizontal unaided FOV extends from the left door through the windshield to the right door.","In some embodiments, the SAEDP is fixed to the left door of the vehicle.","In one embodiment, the vehicle has a single seat (occupied by the occupant).","In another embodiment, the vehicle has two or more front seats and the occupant occupies the leftmost of the two or more front seats.","Different types of SAEDPs may be utilized in different embodiments.","In one embodiment, the SAEDP comprises a passive material, which is less stiff than a standard automotive glass window, having a thickness greater than at least one of the following thicknesses: 1 cm, 2 cm, 5 cm, 10 cm, 15 cm, and 20 cm.","In other embodiments, the SAEDP may include an automotive airbag or a pneumatic pad that is configured to inflate in order to protect the occupant's head against hitting the inner side of the vehicle compartment during collision.","In a similar fashion to how the SAEDP and stiff element are utilized to help protect the left side of the occupant, the same setup may be applied to the right side of the vehicle, in order to help protect that side.","Thus, in some embodiments, the vehicle may further include a second SAEDP located at eye level to the right of the occupant who sits in the front seat, and a second stiff element located at eye level between the second SAEDP and the outside environment.","Optionally, the second SAEDP obstructs at least 20 degrees out of the horizontal unaided FOV to the outside environment to the right of the occupant at eye level, and the computer is further configured to generate a second representation of the outside environment to the right of the occupant.","Some aspects of this disclosure involve an autonomous on-road vehicle that includes a nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) that can cover a side window that enables an occupant of the vehicle to see the outside environment.","The side window is located at eye level of an occupant who sits in the vehicle.","A motor is configured to move the SAEDP over a sliding mechanism between first and second states multiple times without having to be repaired.","A processor is configured to receive, from an autonomous-driving control system, an indication that a probability of an imminent collision reaches a threshold, and to command the motor to move the SAEDP from the first state to the second state.","In the first state the SAEDP does not block the occupant's eye level view to the outside environment, and in the second state the SAEDP blocks the occupant's eye level view to the outside environment in order to protect the occupant's head against hitting the side window during collision.","One non-limiting advantage of the vehicle described above is that it increases the safety of the occupant in the case of a side collision.","In one embodiment, an autonomous on-road vehicle includes a side window 170, a nontransparent SAEDP (e.g., SAEDP 171), a motor 172, and a processor 175.The processor 175 is configured to receive, from an autonomous-driving control system (such as autonomous-driving control system 65), an indication indicating that a probability of an imminent collision reaches a threshold, and to command the motor 172 to move the SAEDP 171 from the first state to the second state.","In the first state the SAEDP 171 does not block the occupant's eye level view to the outside environment, and in the second state, the SAEDP 171 blocks the occupant's eye level view to the outside environment in order to protect the occupant's head against hitting the side window during collision.","Optionally, the processor is configured to command the motor 172 to start moving the SAEDP 171 to the second state at least 0.2 second, 0.5 second, 1 second, or 2 seconds before the expected time of the collision.","The motor 172 is configured to move the SAEDP 171 over a sliding mechanism 173 between first and second states multiple times without having to be repaired.","For example, during the same voyage, the SAEDP 171 may go up and down multiple times without a need for the occupant or anyone else to repair the SAEDP 171 and/or other components (such as motor 172 or the window 170) in order to the SAEDP 171 to be able to continue its operation correctly (i.e., continue moving up and down when needed).","In some examples, the motor 172 is a motor designed to move the SAEDP 171 more than twice, more than 100 times, and/or more than 10,000 times without being replaced.","The side window 170 is located at eye level of an occupant who sits in the vehicle, which enables the occupant to see the outside environment.","In one embodiment, the side window 170 is a power window.","In this embodiment, the power window comprises a window regulator that transfers power from a window motor 177 to the side window glass in order to move it up or down.","The motor 172 is coupled to an SAEDP regulator that transfers power from the motor 172 to the SAEDP 171 in order to move it up or down.","In this embodiment, the SAEDP regulator is located closer to the inner side of the compartment then the window regulator.","Optionally, the motor 172 and the window motor 177 may be of the same type or of different types.","In one embodiment, the SAEDP 171 comprises a passive material, which is less stiff than a standard automotive glass window, having thickness greater than at least one of the following thicknesses: 1 cm, 2 cm, 5 cm, 10 cm, 15 cm, and 20 cm.","Optionally, the vehicle may include a storage space in a door of the vehicle, which is configured to store the SAEDP 171 in the first state.","Additionally or alternatively, the vehicle may include a storage space in the roof of the vehicle, which is configured to store the SAEDP 171 in the first state.","Optionally, the SAEDP 171 may move upwards when switching between the first and second states, and the top of the SAEDP has a profile (such as a triangle or a quarter sphere) which reduces the risk of catching the a part of the occupant (e.g., a finger or limb) or the occupant's clothing, between the top of the SAEDP 171 and an upper frame when moving the SAEDP 171 to the second state.","In one embodiment, when switching the SAEDP 171 quickly between the first and second states, the SAEDP 171 is configured not to cover a range of 1 to 5 cm of the top height of the window.","Optionally, keeping said range unoccupied reduces the risk of catching the occupant's fingers or limb by the edge of the SAEDP 171 when moving the SAEDP 171 to the second state.","In some embodiments, the vehicle may include additional SAEDPs that cover additional regions of the vehicle's compartment (besides the side window 170).","In one example, the vehicle includes an SAEDP 176 that covers at least a portion of the roof of the vehicle.","In some embodiments, the vehicle includes a camera (e.g., camera 178a), which is configured to take video of the outside environment while the SAEDP 171 is in the second state.","Additionally, in these embodiments, the vehicle may include a computer (such as computer 13), which is configured to generate a representation of the outside environment based on the video, and a display configured to present the representation of the outside environment to the occupant.","The display may be physically coupled to the compartment and/or belong to an HMD.","Optionally, the camera is fixed to the SAEDP 171, and thus moves along with the SAEDP 171 when it is moved between the first and second states.","Optionally, the display is fixed to the SAEDP 171, and thus moves along with the SAEDP 171 when it is moved between the first and second states.","Optionally, the display is configured to show, at eye level, a representation of the outside environment when the SAEDP is in the second state.","In one example, the display is a flexible display.","In another example, the camera comprises multiple cameras directed to multiple directions around the vehicle, and the computer is configured to generate at least two different representations of the outside environment, from at least two different points of view, for two occupants who sit in the vehicle.","In some embodiments, in addition to raising the SAEDP 171, one or more of the displays mentioned above is utilized to present the occupant a video of the threat and the predicted trajectory that could result in the collision, in order to explain why the SAEDP 171 is being moved to the second state.","FIG.","24a and FIG.","24b illustrate an example of a vehicle in which the side window may be covered by an SAEDP that can move up and down.","The figures illustrate cross-sections of the vehicle, which show how the SAEDP 171 may move from the first state (in FIG.","24a) to the second state (in FIG.","24b).","The dotted line 179 indicates that the SAEDP 171 does not close the entire gap over the window (e.g., in order to avoid catching the occupant's hair).","The figures also illustrate sliding mechanism 173, which may be utilized to guide and assist in the movement of SAEDP 171.FIG.","24b also illustrates camera 178a and display 178b, which are connected to a processor that generates, based on the video received from the camera, a view of the outside environment when an SAEDP (on the right side of the vehicle) is in the second state.","The view of the outside environment is presented to the occupant on the display 178b.","Camera and display on the left SAEDP 171, which correspond to camera 178a and display 178b, are not shown in the figure in order to make it clearer; however it is to be understood that such camera and display may be fitted to any relevant moving SAEDP.","In one embodiment, the mechanism that moves the SAEDP 171 between the first and second states (referred to as the “SAEDP mechanism”) is similar to a power window regulator that moves an automobile window up and down.","As with automobile power windows, the SAEDP regulator may be powered by an electric motor, which may come with the SAEDP regulator as one unit, or as a system that enables the motor or regulator to be replaced separately.","The SAEDP mechanism includes a control system, a motor, a gear reduction, a sliding mechanism and the SAEDP, which are usually fixed on the door, but may alternatively be fixed on the roof as disclosed below.","The sliding mechanism may have different architectures, such as Bowden type, double Bowden type, cable spiral, or crossed levers.","In a first example, the SAEDP mechanism is similar to a double Bowden power window mechanism, in which the SAEDP 171 is fixed on two supports respectively constrained along two rails.","The control system drives the motor that wraps two Bowden cables, which move two supports and, consequently, the SAEDP 171.A Bowden cable transmits mechanical force through the movement of an inner cable relative to an outer housing, and in the case of a DC motor, the basic operations of the motor are accomplished by reversing the polarity of its power and ground input.","In a second example, the SAEDP mechanism is similar to a gear-drive type power window regulator; in this case, the SAEDP mechanism includes an SAEDP motor to power the mechanism, gear drive and geared arm to move the SAEDP 171 between the first and second states, and an SAEDP holding bracket to hold the SAEDP 171.In a third example, the SAEDP mechanism is similar to a cable type power window regulator; in this case, the SAEDP regulator includes an SAEDP motor that drives a wire cable though a mechanism, a series of pulleys that guide the cable, and a regulator carriage attached to the cable and to the SAEDP 171 and slides on the regulator track.","One or more tracks may be mounted vertically inside the door panel that serves as a guide piece when the SAEDP 171 slides up and down.","Depending on the design, the setup may have one main regulator track in the center of the door, or have a track on each side of the SAEDP.","In a fourth example, the SAEDP regulator is similar to a scissor power window regulator; in this case, a motor operates a gear wheel that raises and lowers the SAEDP 171 by the use of a scissor action of rigid bars.","The motor that moves the SAEDP 171 over the sliding mechanism may be any suitable motor, such as a DC electric motor, an AC electric motor, or a pneumatic motor.","In one embodiment, the indication that the probability of an imminent collision reaches a threshold is received from the autonomous-driving control system 65 that calculates the probability based on the trajectory of the vehicle and information about the road.","Optionally, the information about the road may be received from one of more of the following sources: a sensor mounted to the vehicle, a sensor mounted on a nearby vehicle, a road map, a stationary traffic controller nearby the vehicle, and a central traffic controller that communicates with the vehicle via wireless channel.","In one embodiment, the processor 175 is further configured to receive an updated indication that the probability of the imminent collision does not reach a second threshold, and to command the motor to move the SAEDP to the first state.","In this embodiment, the second threshold denotes a probability for a collision that is equal or lower than the threshold.","FIG.","25a and FIG.","25b illustrate a motor configured to move a front nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) between first and second states.","Some aspects of this disclosure involve an autonomous on-road vehicle that includes an outer nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) mounted to the front side of the vehicle during normal driving, such that the SAEDP is in front of and at eye level of an occupant who sits in a front seat of the vehicle.","Additionally, the vehicle includes a camera that is mounted to the vehicle and is configured to take video of the outside environment in front of the occupant, and a computer configured to generate, based on the video, a representation of the outside environment at eye level for the occupant.","One non-limiting advantage of the vehicle described above is that it increases the safety of a pedestrian in case of a vehicle-pedestrian collision, without prohibiting the occupant of the vehicle from receiving a frontal view of the outside environment.","FIG.","26a illustrates one embodiment of an autonomous on-road vehicle that includes outer nontransparent SAEDP 190, which is mounted to the front side of the vehicle during normal driving, such that the SAEDP 190 is in front of and at eye level of an occupant who sits in a front seat of the vehicle.","The SAEDP 190 is less stiff than a standard automotive glass window and is designed to absorb some of the crashing energy transmitted to a pedestrian during a pedestrian-vehicle collision.","Additionally, the vehicle includes a camera (such as camera 142), which is mounted to the vehicle and is configured to take video of the outside environment in front of the occupant, and a computer (such as computer 143), which is configured to generate, based on the video, a representation of the outside environment at eye level for the occupant.","Optionally, the representation is generated from the point of view of the occupant.","Optionally, the vehicle includes a display configured to present the representation to the occupant.","For example, the display may belong to an HMD worn by the occupant.","In another example, the display may be coupled to the compartment of the vehicle, and may be a flexible display.","The SAEDP 190 may be implemented utilizing various approaches in different embodiments described herein.","In one embodiment, the SAEDP 190 comprises a passive material.","Optionally, the SAEDP 190 has thickness greater than at least one of the following thicknesses: 1 cm, 2 cm, 5 cm, 10 cm, 15 cm, and 20 cm.","In another embodiment, the SAEDP 190 comprises an automotive airbag configured to inflate in order to protect the pedestrian.","FIG.","26b illustrates an outer SAEDP 190 that includes two air bags 192 configured to absorb some of the crashing energy transmitted to a pedestrian during a pedestrian-vehicle collision.","Optionally, the airbag has a stowed condition and an inflated condition.","The airbag is coupled to an inflator configured to inflate the airbag with gas, and the airbag is located, in the stowed condition, at eye level in front of the occupant.","In this embodiment, the vehicle further includes an autonomous-driving control system, such as autonomous-driving control system 65, which is configured to calculate a probability of pedestrian-vehicle collision, based on measurements of sensors mounted to the vehicle, and to command the airbag to inflate before the pedestrian head hits the vehicle.","In yet another embodiment, the SAEDP 190 comprises a pneumatic pad configured to inflate in order to protect the pedestrian.","In this embodiment, the vehicle further includes an autonomous-driving control system, such as autonomous-driving control system 65, which is configured to calculate a probability of pedestrian-vehicle collision, based on measurements of sensors mounted to the vehicle, and to command the pneumatic pad to start inflate at least 0.5 second before the expected time of the collision in order to protect the pedestrian.","Optionally, the pneumatic pad is reusable, and can be used multiple times without the need to be repaired.","For example, the vehicle comprises a mechanism to deflate and/or stow the pneumatic pad, without requiring its repair and/or replacement.","Some aspects of this disclosure involve an autonomous on-road vehicle that includes a window located at eye level of an occupant who sits in a front seat of the vehicle (e.g., a windshield), a reusable nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP), a motor, and a processor.","The window enables the occupant to see the outside environment.","The motor is configured to move the SAEDP over a sliding mechanism between first and second states multiple times without having to be repaired.","In the first state the SAEDP does not block the occupant's eye level frontal view to the outside environment, and in the second state the SAEDP blocks the occupant's eye level frontal view to the outside environment.","Additionally, in the second state the SAEDP can absorb some of the crashing energy transmitted to a pedestrian during a pedestrian-vehicle collision.","The processor is configured to receive, from an autonomous-driving control system, an indication indicative of whether a probability of an imminent pedestrian-vehicle collision reaches a threshold.","Responsive to receiving an indication of an imminent collision (e.g., within less than 2 seconds), the processor is configured to command the motor to move the SAEDP from the first state to the second state.","One non-limiting advantage of the vehicle described above is that it increases the safety of a pedestrian in case of a vehicle-pedestrian collision, without prohibiting the occupant of the vehicle from receiving a frontal view of the outside environment during normal driving.","FIG.","27a and FIG.","27b illustrate a motorized external SAEDP 121 that can move between first and second states multiple times.","The figures illustrate how the SAEDP 121 can move from the first state (in FIG.","27a) to the second state (FIG.","27b) by having the motor 122 move the SAEDP 121 over sliding mechanism 123.Additionally, the figures illustrate optional camera 126 that is embedded in the SAEDP 121, and which may provide video to a processor configured to generate a representation of the outside environment when the SAEDP 121 is in the second state.","In one embodiment, an autonomous on-road vehicle includes window 120, reusable SAEDP 121, motor 122, and processor 124.The window 120, which is located at eye level of an occupant who sits in a front seat of the vehicle, and which may be a windshield, enables the occupant to see the outside environment.","The SAEDP 121 is reusable, i.e., it may be moved multiple times without the need to replace it or repair it after each use.","The SAEDP 121 may be implemented utilizing various approaches in different embodiments described herein.","In one embodiment, the SAEDP 121 comprises a passive material.","Optionally, the SAEDP 121 has thickness greater than at least one of the following thicknesses: 1 cm, 2 cm, 5 cm, 10 cm, 15 cm, and 20 cm.","In another embodiment, the SAEDP 121 comprises a pneumatic pad configured to inflate in order to protect the pedestrian.","Optionally, the pneumatic pad is reusable, and the processor 124 is configured to command the pneumatic pad to start inflate at least 0.5 second before the expected time of the pedestrian-vehicle collision.","The motor 122 is configured to move the SAEDP 121 over a sliding mechanism 123 between first and second states multiple times without having to be repaired.","In the first state the SAEDP 121 does not block the occupant's eye level frontal view to the outside environment, and in the second state the SAEDP 121 blocks the occupant's eye level frontal view to the outside environment.","When in the second state, the SAEDP 121 is configured to absorb some of the crashing energy transmitted to a pedestrian during a pedestrian-vehicle collision.","The processor 124 is configured to receive, from an autonomous-driving control system (such as autonomous-driving control system 65), an indication indicative of whether a probability of an imminent pedestrian-vehicle collision reaches a threshold.","Optionally, most of the time the vehicle travels, the processor 124 does not provide an indication that the probability reaches the threshold.","Responsive to receiving an indication of an imminent collision (e.g., within less than 2 seconds), the processor 124 is configured to command the motor 122 to move the SAEDP 121 from the first state to the second state.","Optionally, the processor 124 is configured to command the motor to start moving the SAEDP 121 to the second state at least 0.2 second, 0.5 second, 1 second, or 2 seconds before the pedestrian-vehicle collision in order to protect the pedestrian.","In one example, the vehicle includes a sensor configured to detect the distance and angle between the vehicle and a pedestrian, and the autonomous-driving control system calculates the probability of the imminent pedestrian-vehicle collision based on the data obtained from the sensor, the velocity of vehicle and the possible maneuver.","In one embodiment, the processor 124 is further configured to receive an updated indication that indicates the probability of the imminent pedestrian-vehicle collision does not reach a second threshold, and to command the motor 122 to move the SAEDP to the first state.","Optionally, the second threshold denotes a probability for a pedestrian-vehicle collision that is equal or lower than the threshold.","In one embodiment, the vehicle includes a camera (such as camera 126), which is configured to take video of the outside environment while the SAEDP 121 is in the second state.","Additionally, in this embodiment, the vehicle may further include a computer configured to generate, based on the video, a representation of the outside environment, and a display configured to present the representation of the outside environment to the occupant while the SAEDP 121 is in the second state.","Optionally, the camera 126 is fixed to the SAEDP 121 from the outer side, and thus moves with the SAEDP 121 when it moves between the first and second states.","Optionally, the display is fixed to the SAEDP 121 from the inner side, and thus also moves with the SAEDP 121 when it moves between the first and second states; the occupant can see the display via the window 120 when the SAEDP is in the second state.","In an alternative embodiment, the display is physically coupled to the compartment (such as a windshield that also functions as a display) and/or comprised in an HMD worn by the occupant.","In addition to, or instead of, moving an SAEDP when a collision is imminent, in some embodiments, an imminent collision may prompt a raise of one or more power windows in the vehicle.","This approach is illustrated in the following embodiment.","In one embodiment, a safety system for an occupant of an autonomous on-road vehicle includes an automobile power window and an autonomous-driving control system (such as autonomous-driving control system 65).","The autonomous-driving control system is configured to calculate probability of an imminent collision based on data received from sensors coupled to the vehicle.","Responsive to detecting that the probability reaches a threshold, and at least one second before the expected collision, the autonomous-driving control system commands the power window to rise.","In this embodiment, a raised power window provides an improved safety for the occupant of the vehicle during collision compared to a lowered power window.","Optionally, responsive to detecting that the probability reaches the threshold, and at least two seconds before the expected collision, the autonomous-driving control system is configured to command the power window to rise.","In one embodiment, the vehicle further includes an SAEDP coupled to the power window from the inside (e.g., as illustrated in FIG.","24a and FIG.","24b).","In one embodiment, the power window is nontransparent, and the safety system for the occupant includes a display coupled to the power window from the inside.","The display is configured to present to the occupant a video see-trough (VST) of the outside environment that is generated based on a video camera pointed at the outside environment.","In another embodiment, the power window is made of a nontransparent material, which is stronger than a standard automotive tempered glass having the same dimensions.","In this embodiment, the vehicle further comprises a camera configured to take video of the outside environment (such as camera 178a), and a computer configured to generate a VST to the outside environment based on the video.","Optionally, the camera is physically coupled to the power window, such that the camera is raised and lowered with the power window.","Additionally or alternatively, the camera may be coupled to an element of the vehicle that is not the power window, such that the camera does not move up and down when the power window is raised and lowered.","Optionally, the vehicle further includes a display coupled to the inner side of the power window, such that the display is at eye level when the power window is raised, and below eye level when the power window is lowered; the display is configured to present the VST to the occupant.","Optionally, the occupant wears an HMD, and the computer is configured to present the VST to the occupant on the HMD when the power window is raised, and not to present the VST to the occupant on the HMD when the power window is lowered.","With autonomous vehicles, it is not necessary for occupants to sit.","Some aspects of this disclosure involve autonomous vehicles in which an occupant of the vehicle may lay down.","Such a design for an autonomous vehicle has the advantage of enabling a more comfortable position for certain activities (e.g., relaxing or sleeping).","Additionally, such a vehicle may be built to be lower than traditional vehicles, which can offer advantages in terms of increased safety (e.g., a lower center of gravity offers better stability) and better vehicle aerodynamics.","In order to increase the safety of the occupant, various forms of padding may be used in the compartment of the vehicle.","In some embodiments, an autonomous on-road vehicle designed for lying down includes a closed compartment and a mattress, having an average thickness of at least 3 cm, which covers at least 50% of the compartment floor.","In the compartment, there is a nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP), having an average thickness of at least 1 cm, which covers at least 50% of the compartment side walls and at least 60% of the compartment front wall during normal driving.","Optionally, the SAEDP is supported by a stiff element that resists deformation during a collision in order to reduce compartment intrusion.","Additionally, the vehicle includes a camera configured to take video of the outside environment, a computer configured to generate a representation of the outside environment based on the video, and a display configured to present the representation to the occupant.","In one embodiment, an autonomous on-road vehicle designed for lying down includes a closed compartment 210, a mattress 211, an SAEDP 212 covering portions of the compartment 210, a camera (e.g., the structure 147 that houses multiple cameras), a computer (e.g., the computer 143), and a display 215.FIG.","28 illustrates one embodiment of a vehicle compartment 210 in which an occupant may lay down.","In the figure, the occupant is lying down on mattress 211, which covers the floor of the compartment 210, and is watching a movie on the display 215.The SAEDP 212 covers the front, roof, and back of the compartment 210.It is to be noted that the SAEDP 212 also covers portions of the side walls of the compartment 210, however, this is not illustrated to enable a clearer image of the embodiment.","The figure also includes an airbag 216, which may be inflated below the SAEDP 212 in order to protect the occupant and restrain his/her movement in the case of a collision.","The mattress 211 covers at least 50% of the compartment floor.","Optionally, the mattress 211 covers at least 80% of the compartment floor.","In one embodiment, the mattress 211 has an average thickness of at least 3 cm.","In other embodiments, the average thickness of the mattress 211 is greater than at least one of the following thicknesses: 5 cm, 7 cm, 10 cm, 20 cm, and 30 cm.","The SAEDP 212 is a nontransparent SAEDP, having an average thickness of at least 1 cm.","Optionally, the SAEDP 212 covers at least 50% of the compartment side walls and at least 60% of the compartment front wall during normal driving.","In one embodiment, the average thickness of the SAEDP 212 is greater than at least one of the following thicknesses: 2 cm, 3 cm, 5 cm, 10 cm, 15 cm, and 20 cm.","In another embodiment, the SAEDP 212 covers at least 80% of the compartment side walls and at least 80% of the compartment front wall.","In yet another embodiment, the SAEDP covers at least 50% of the compartment roof.","In still another embodiment, the mattress and the SAEDP cover essentially the entire compartment interior.","In addition to the SAEDP 212, in some embodiments additional measures may be employed in order to improve the safety of the occupant.","In one embodiment, the vehicle includes an automotive airbag configured to deploy in front of the SAEDP 212 in order to protect the occupant, in addition to the SAEDP 212, against hitting the inner side of the vehicle compartment during a collision.","It is noted that the meaning that the airbag deploys in front of the SAEDP is that the airbag deploys towards the inner side of the compartment.","Optionally, the airbag has a stowed condition and an inflated condition, and the airbag is coupled to an inflator configured to inflate the airbag with gas upon computing a predetermined impact severity.","The stowed airbags may be stored in various positions, such as stored essentially in the middle of the front wall, stored essentially in the middle of the rear wall, stored in the side walls (possibly two or more horizontally spaced airbags), and stored in the roof (possibly one or more airbags towards the front of the compartment and one or more airbags towards the rear of the compartment).","In some embodiments, various additional safety measures may be utilized to improve the safety of the occupant while traveling, such as a sleeping net and/or a safety belt, as described for example in U.S. Pat.","Nos.","5,536,042 and 5,375,879.Stiff element 213 is configured to support the SAEDP 212 and to resist deformation during a collision in order to reduce compartment intrusion.","Part of the stiff element 213 is located, during normal driving, at eye level between the SAEDP 212 and the outside environment.","Optionally, the stiff element covers, from the outside, more than 80% of the SAEDP on the compartment side walls.","Optionally, the vehicle also includes a crumple zone located at eye level between the stiff element 213 and the outside environment.","In another embodiment, the vehicle includes a pneumatic pad configured to inflate in order to protect the occupant, in addition to the SAEDP 212, against hitting the inner side of the vehicle compartment during a collision.","Optionally, the pneumatic pad is configured to deploy in front of the SAEDP 212 towards the inner side of the compartment.","Alternatively, the pneumatic pad is located between the SAEDP 212 and the stiff element 213, and is configured to deploy behind the SAEDP 212.The pneumatic pad may be mounted to various locations, such as mounted to the front wall, mounted to the rear wall, mounted to the side walls, and/or mounted to the roof.","The camera is configured to take video of the outside environment.","The computer is configured to generate a representation of the outside environment based on the video.","Optionally, the representation is generated from the point of view of the occupant.","The display 215 is configured to present the representation to the occupant.","In one embodiment, the display 215 is comprised in an HMD, and the vehicle further comprises a communication system configured to transmit the representation to the HMD.","In another embodiment, the display 215 is physically coupled to at least one of the SAEDP 212 and the stiff element 213 at eye level of the occupant.","Optionally, the display 215 is a flexible display.","For example, the display 215 may be a flexible display that is based on at least one of the following technologies and their variants: OLED, organic thin film transistors (OTFT), electronic paper (e-paper), rollable display, and flexible AMOLED.","Optionally, the display 215 is flexible enough such that it does not degrade the performance of the SAEDP by more than 20% during a collision.","Having a vehicle compartment that is designed to allow an occupant to lay down comfortably can be done using various compartment designs, which may be different from the designs used in standard vehicles, in which occupants primarily sit up.","In one example, the vehicle does not have an automotive seat with a backrest and safety belt, which enables the occupant to sit straight in the front two thirds of the compartment.","In another example, the vehicle is designed for a single occupant, and the average distance between the mattress and the compartment roof is below 80 cm.","In still another example, the vehicle is designed for a single occupant, and the average distance between the mattress and the compartment roof is below 70 cm.","In still another example, the vehicle is designed for a single occupant, and the average distance of the compartment roof from the road is less than 1 meter.","And in yet another example the vehicle is designed for a single occupant, and the average distance of the compartment roof from the road is less than 80 cm.","It is to be noted that the use of the terms “floor”, “roof”, “side walls”, and “front wall” with respect to the compartment are to be viewed in their common meaning when one considers the compartment to be a mostly convex hull in 3D, such as having a shape that resembles a cuboid.","Thus, for example, an occupant whose face faces forward, will see the front wall ahead, the floor when looking below, the roof when looking above, and a side wall when looking to one of the sides (left or right).","In embodiments that do not resemble cuboids, alternative definitions for these terms may be used based on the relative region (in 3D space) that each of the portions of the compartment occupy.","For example, the floor of the compartment may be considered to be any portion of the compartment which is below at least 80% of the volume of the compartment.","Similarly, the roof may be any portion of the compartment that is above at least 80% of the volume of the compartment.","The front wall may be any portion of the compartment that is ahead of at least 80% of the volume of the compartment, etc.","Note that using this alternative definitions, some portions of the compartment may be characterized as belonging to two different regions (e.g., the front wall and the roof).","Some aspects of this disclosure involve an autonomous on-road vehicle that includes a compartment having a large mirroring element located in front of an occupant who sits in a front seat of the compartment.","Optionally, the mirroring element has height and width exceeding 25×25 cm, such that it covers a square that is at least those dimensions.","Optionally, the mirroring element captures a region corresponding to at least 10×10 degrees, including a region spanning from the horizon to 10° below the horizon, of the occupant's forward field of view during normal driving.","Additionally, the mirroring element provides an effect of reflecting more than 25% of the light arriving from the occupant's direction.","In some embodiments, the vehicle has an advantage that it can increase the perceived compartment volume, which can make travelling in the vehicle more pleasurable for some people.","FIG.","29 illustrates one embodiment of a vehicle having a front mirroring element.","The figure illustrates how the occupant 222 can see her reflection 223 in the mirroring element 220.In one embodiment, the mirroring element 220 is located in front of an occupant who sits in a front seat of the vehicle.","The mirroring element 220 provides an effect of reflecting more than 25% of the light arriving from the occupant's direction.","Optionally, the mirroring element 220 provides an effect of reflecting more than at least one of 50%, 80%, and 90% of the light arriving from the occupant's direction.","Optionally, the mirroring element 220 increases the volume of the vehicle compartment as perceived by the occupant due to the reflection effect.","In one embodiment, the mirroring element 220 has height and width exceeding 25×25 cm, such that it covers a square that is at least those dimensions.","Optionally, the mirroring element 220 captures a region corresponding to at least 10×10 degrees, including a region spanning from the horizon to 10° below the horizon, of the occupant's forward field of view during normal driving.","Optionally, the height and width of the mirroring element 220 is above 50×40 cm, and the mirroring element captures above 30×30 degrees of the occupant's field of view, including a region spanning from the horizon to 30° below the horizon.","Optionally, the mirroring element 220 covers more than 25% of the area where a conventional windshield of a normal non-autonomous on-road vehicle in year 2016 is expected to be located.","The mirroring element 220 may be implemented in different ways, in different embodiments.","In one embodiment, the mirroring element 220 comprises an optical mirror that is essentially flat and perpendicular to the ground.","In this embodiment, most of the effect of reflecting is generated by the optical mirror.","In one example, an optical mirror that is essentially flat and perpendicular to the ground refers to an optical mirror having a radius of curvature greater than a meter and a deviation below ±30° from the perpendicular to the ground.","In another embodiment, the mirroring element 220 comprises a Fresnel type optical reflector comprising many reflecting prisms.","In this embodiment, the Fresnel type optical reflector is not flat, but the reflecting prisms are arranged in angles that reflect the light from the occupant such as to imitate a flat mirror.","In one embodiment, the mirroring element 220 comprises an electronic display that operates based on a camera 221 configured to take video of the occupant 222, and a computer 224 configured to generate a digital representation of the occupant 223 based on the video of the occupant.","In this case, most of the effect of reflecting is generated by light emitted by the electronic display (which is the output of the video of the occupant as generated by the computer 224).","Due to the close proximity between the at least one camera 221 and the occupant, it may be necessary to stitch the reflecting effect of a large area from multiple cameras that capture the occupant from different angles.","In one example, the camera 221 comprises first and second cameras, located to the right and left of the occupant, respectively.","In another example, the camera 221 comprises first and second cameras, located above the level of the occupant's nose and below the level of the occupant's collarbone, respectively, and less than 80 cm away from the occupant.","In still another embodiment, the effect of reflecting is achieved by a digital mirror that comprises multiple cameras embedded within the digital mirror and configured to take images of the occupant, and multiple light emitting pixels configured to emit light rays that generate the effect of reflecting.","In one embodiment, the mirroring element 220 comprises an electronic display, and the vehicle further includes a camera configured to take video of the outside environment in front of the occupant, and a computer configured to generate, based on the video, a representation of the outside environment in front of the occupant at eye level, for displaying on the mirroring element 220.In addition to the effect of reflecting, in some embodiments the mirroring element 220 may also be configured to operate in a second state in which it provides an effect of reflecting less than 20% of the light arriving from the occupant's direction, and to present to the occupant the representation of the outside environment.","Here, presenting the representation may imitate a transparent windshield to the outside environment.","The vehicle may also include, in some embodiments, a display configured to present to the occupant, at eye level in front of the occupant, the representation of the outside environment instead of, or in addition to, the effect of reflecting.","Optionally, the vehicle may include a user interface configured to enable the occupant to switch between seeing the effect of reflecting and seeing the representation of the outside environment.","In one example, the display is comprised in a head-mounted display (HMD).","In another example, the display is mechanically coupled to the compartment, and/or the mirroring element comprises the display.","As described above, the effect of reflecting light that comes from the direction of the occupant may be obtained, in some embodiments, utilizing an HMD.","The following is a more detailed example of such an embodiment.","In one embodiment, an autonomous on-road vehicle includes a compartment comprising a front seat, a camera, a computer, a communication module, and an HMD.","The camera is physically coupled to the vehicle, configured to take images of an occupant who sits in the front seat.","The computer is configured to generate, based on the images, a video that shows a mirror effect.","Herein, the “mirror effect” involves presenting the occupant with an image that is similar to an image that the occupant would see had there been an actual mirror in front of the occupant.","Optionally, the system enables the occupant to have control on the synthetic mirror effect, such as control on the distance between the occupant and her image, and/or control on the width of the image.","The communication module is configured to transmit the video to a head-mounted display (HMD) worn by the occupant, and the HMD is configured to present the video to the occupant, such that the occupant sees a representation of his or her reflection when looking forward at eye level.","Optionally, the HMD is selected from the group comprising: a virtual reality headset, an augmented reality headset, and mixed reality headset.","Optionally, the video presented to the occupant captures at least 30×30 degrees of the occupant's field of view, spanning at least from the horizon to 30° below the horizon.","In one embodiment, the vehicle described above further includes a second camera configured to take a second set of images of the outside environment in front of the occupant.","In this embodiment, the computer is further configured to generate a representation of the outside environment based on the second set of images, and the HMD is configured to present the representation of the outside environment instead of the video that shows the mirror effect or in addition to the video that shows the mirror effect.","In one embodiment, the vehicle described above may include multiple cameras that capture images that are utilized by the computer to generate the video that shows the mirror effect.","In one example, the vehicle comprises at least first and second cameras, which are located to the right and left of the occupant, respectively.","In another example, the vehicle comprises at least first and second cameras, located above the level of the occupant's nose and below the level of the occupant's collarbone, respectively, and which are less than 80 cm away from the occupant.","Some aspects of this disclosure involve utilizing one or more nontransparent side beams in order to help protect the occupant in a case of a collision.","The one or more side beams are stiffer than automotive laminated glass.","In one example, a side beam comprises a high tensile steel pipe and pressed material.","In another example, a side beam comprises an aluminum extruded shape.","In one embodiment, an autonomous on-road vehicle that weighs less than 1500 kg without batteries includes a nontransparent side beam, which is stiffer than automotive laminated glass, and is located during normal driving to the left and at eye level of an occupant who sits in a front seat.","The vehicle also includes a camera configured to take video of the outside environment to the left of the occupant, and a computer configured to generate for the occupant, based on the video, a representation of the outside environment to the left of the occupant at eye level.","Optionally, the representation is presented to the occupant using a display.","In one example, the display is comprised in a head-mounted display (HMD), and the vehicle further comprises a communication system configured to transmit the representation to the HMD.","In another example, the display is coupled to the inner side of the compartment.","The following is a description of an embodiment of a vehicle in which one or more side beams may be utilized to help protect the left side of a vehicle (and an occupant therein).","In one embodiment, an autonomous on-road vehicle includes a nontransparent side beam, a camera (e.g., the camera 161), and a computer (e.g., the computer 143).","Optionally, the vehicle weighs less than 1500 kg without batteries.","The nontransparent side beam, which is stiffer than automotive laminated glass, is located, during normal driving, at eye level to the left of an occupant who sits in a front seat of the vehicle.","Optionally, the side beam is at least 60 cm long and at least 1 cm wide (herein “cm” refers to centimeters).","In one example, the side beam comprises a high tensile steel pipe and pressed material.","In another example, the side beam comprises an aluminum extruded shape.","The camera configured to take video of the outside environment to the left of the occupant.","The computer is configured to generate for the occupant, based on the video, a representation of the outside environment to the left of the occupant at eye level.","Optionally, the representation is generated from the point of view of the occupant, and the vehicle further includes a display configured to present the representation to the occupant.","In one example, the display is comprised in a head-mounted display (HMD), and the vehicle further comprises a communication system configured to transmit the representation to the HMD.","In another example, the display is coupled to the inner side of the compartment.","In some embodiments, a plurality of beams, which may be similar to the side beam described above, may be located in the region of the left side of the vehicle.","It is to be noted that the plurality of beams may not necessarily all have the same dimensions or be made of the same exact materials.","Optionally, the plurality of beams may be connected in various ways in order to form a structure that can better resist compartment deforming in the case of a collision.","For example, in one embodiment, the vehicle includes an additional side beam that is not parallel to the side beam and crosses it to form an “X” shaped structure.","Herein, an “X” shaped structure refers to any structure of two nonparallel beams that cross, and the two do not necessarily form a symmetric “X” (e.g., a symmetric “X” may be obtained when the two beams are of equal length and cross at their centers).","This structure is illustrated in FIG.","30a where beams 231 and 232 cross to form an “X” shape structure.","It is to be noted that the beam 231 is at eye level (i.e., at least a portion of the beam 231 is at the same height as a typical occupant's eyes).","FIG.","30a illustrates one example of a configuration of a plurality of beams located in the left side of the vehicle.","Different designs of vehicles may benefit from utilizing one or more sides beam as described above.","In one embodiment, the side beam is embedded in a movable structure that changes its location with respect to the vehicle compartment.","For example, the side beam may be part of a left door of the vehicle.","In another embodiment, the side beam is embedded in the vehicle compartment itself and does not change its location with respect to the rest of the compartment.","For example, the side beam may be placed in a compartment wall to the left of the occupant.","In order to better protect the occupant from injury due to hitting the head against the side of the vehicle, in some embodiments, the vehicle may comprise a nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) located at eye level between the side beam and the occupant.","The SAEDP is less stiff than a standard automotive glass window.","In one example, the SAEDP comprises a passive material.","In another example, the SAEDP includes an airbag.","And in still another example, the SAEDP includes a pneumatic pad.","Optionally, the vehicle includes a display on which the representation of the outside environment may be presented to the occupant.","Optionally, the display is supported by the SAEDP and/or the side beam.","Optionally, the display is a flexible display.","In a similar fashion to the utilization of beams on the left side of the vehicle, in some embodiments, one or more beams may be used to help protect the occupant's right side.","For example, in one embodiment, the vehicle includes a second side beam, located at eye level to the right of the occupant, and a second camera configured to take video of the outside environment to the right of the occupant.","In this embodiment, the computer is further configured to generate a second representation of the outside environment to the right of the occupant.","Some aspects of this disclosure involve utilizing one or more nontransparent beams in order to help protect the occupant in a case of a collision.","The one or more beams are stiffer than automotive laminated glass.","In one example, a nontransparent beam comprises a high tensile steel pipe and pressed material.","In another example, a nontransparent beam comprises an aluminum extruded shape.","In one embodiment, an autonomous on-road vehicle that weighs less than 1500 kg without batteries includes a nontransparent beam, which is stiffer than automotive laminated glass, and is fixed at eye level in front of an occupant who sits in a front seat of the vehicle during normal driving.","The vehicle also includes a camera configured to take video of the outside environment in front of the occupant, and a computer configured to generate for the occupant, based on the video, a representation of the outside environment in front of the occupant at eye level.","Optionally, the representation is presented to the occupant using a display.","In one example, the display is comprised in a head-mounted display (HMD), and the vehicle further comprises a communication system configured to transmit the representation to the HMD.","In another example, the display is coupled to the inner side of the compartment.","The following is a description of an embodiment of a vehicle in which one or more nontransparent beams may be utilized to help protect the vehicle's front (and an occupant therein).","In one embodiment, an autonomous on-road vehicle includes a nontransparent beam, a camera (e.g., the camera 142), and a computer (e.g., the computer 143).","Optionally, the vehicle weighs less than 1500 kg without batteries.","The nontransparent beam, which is stiffer than automotive laminated glass, is located, during normal driving, at eye level in front an occupant who sits in a front seat of the vehicle.","Optionally, the nontransparent beam is at least 60 cm long and at least 1 cm wide (herein “cm” refers to centimeters).","In one example, the nontransparent beam comprises a high tensile steel pipe and pressed material.","In another example, the nontransparent beam comprises an aluminum extruded shape.","The camera configured to take video of the outside environment in front of the occupant.","The computer is configured to generate for the occupant, based on the video, a representation of the outside environment in front of the occupant at eye level.","Optionally, the representation is generated from the point of view of the occupant, and the vehicle further includes a display configured to present the representation to the occupant.","In one example, the display is comprised in a head-mounted display (HMD), and the vehicle further comprises a communication system configured to transmit the representation to the HMD.","In another example, the display is coupled to the inner side of the compartment.","In some embodiments, a plurality of beams, which may be similar to the nontransparent beam described above, may be located in the front of the vehicle.","It is to be noted that the plurality of beams may not necessarily all have the same dimensions or be made of the same exact materials.","Optionally, the plurality of beams may be connected in various ways in order to form a structure that can better resist compartment deformation in the case of a collision.","For example, in one embodiment, the vehicle includes an additional nontransparent beam that is not parallel to the nontransparent beam and crosses it to form an “X” shaped structure.","This structure is illustrated in FIG.","30b where beams 235 and 236 cross to form an “X” shape structure.","Both of the beams 235 and 236 are at eye level (i.e., at least a portion of each beam is at the same height as a typical occupant's eyes).","FIG.","30b illustrates one example of a configuration of a plurality of beams located in the front of the vehicle.","Different designs of vehicles may benefit from utilizing one or more nontransparent beam as described above.","In one embodiment, the nontransparent beam is embedded in a movable structure that changes its location with respect to the vehicle compartment.","For example, the nontransparent beam may be part of a front door through which the occupant may enter the vehicle.","In another embodiment, the nontransparent beam is embedded in the vehicle compartment itself and does not change its location with respect to the rest of the compartment.","For example, the nontransparent beam may be placed in a compartment wall in front of the occupant.","In order to better protect the occupant from injury (e.g., during a collision), in some embodiments, the vehicle may comprise a nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) located at eye level between the nontransparent beam and the occupant.","The SAEDP is less stiff than a standard automotive glass window.","In one example, the SAEDP comprises a passive material.","In another example, the SAEDP includes an airbag.","And in still another example, the SAEDP includes a pneumatic pad.","Optionally, the vehicle includes a display on which the representation of the outside environment may be presented to the occupant.","Optionally, the display is coupled to the inner side of the compartment.","Optionally, the display is a flexible display.","Various embodiments described herein include a processor and/or a computer.","For example, the autonomous-driving control system may be implemented using a computer and generation of a representation of the outside environment is done using a processor or a computer.","The following are some examples of various types of computers and/or processors that may be utilized in some of the embodiments described herein.","FIG.","31a and FIG.","31b are schematic illustrations of possible embodiments for computers (400, 410) that are able to realize one or more of the embodiments discussed herein.","The computer (400, 410) may be implemented in various ways, such as, but not limited to, a server, a client, a personal computer, a network device, a handheld device (e.g., a smartphone), and/or any other computer form capable of executing a set of computer instructions.","The computer 400 includes one or more of the following components: processor 401, memory 402, computer readable medium 403, user interface 404, communication interface 405, and bus 406.In one example, the processor 401 may include one or more of the following components: a general-purpose processing device, a microprocessor, a central processing unit, a complex instruction set computing (CISC) microprocessor, a reduced instruction set computing (RISC) microprocessor, a very long instruction word (VLIW) microprocessor, a special-purpose processing device, an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), a digital signal processor (DSP), a distributed processing entity, and/or a network processor.","Continuing the example, the memory 402 may include one or more of the following memory components: CPU cache, main memory, read-only memory (ROM), dynamic random access memory (DRAM) such as synchronous DRAM (SDRAM), flash memory, static random access memory (SRAM), and/or a data storage device.","The processor 401 and the one or more memory components may communicate with each other via a bus, such as bus 406.The computer 410 includes one or more of the following components: processor 411, memory 412, and communication interface 413.In one example, the processor 411 may include one or more of the following components: a general-purpose processing device, a microprocessor, a central processing unit, a complex instruction set computing (CISC) microprocessor, a reduced instruction set computing (RISC) microprocessor, a very long instruction word (VLIW) microprocessor, a special-purpose processing device, an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), a digital signal processor (DSP), a distributed processing entity, and/or a network processor.","Continuing the example, the memory 412 may include one or more of the following memory components: CPU cache, main memory, read-only memory (ROM), dynamic random access memory (DRAM) such as synchronous DRAM (SDRAM), flash memory, static random access memory (SRAM), and/or a data storage device Still continuing the examples, the communication interface (405,413) may include one or more components for connecting to one or more of the following: an inter-vehicle network, Ethernet, intranet, the Internet, a fiber communication network, a wired communication network, and/or a wireless communication network.","Optionally, the communication interface (405,413) is used to connect with the network 408.Additionally or alternatively, the communication interface 405 may be used to connect to other networks and/or other communication interfaces.","Still continuing the example, the user interface 404 may include one or more of the following components: (i) an image generation device, such as a video display, an augmented reality system, a virtual reality system, and/or a mixed reality system, (ii) an audio generation device, such as one or more speakers, (iii) an input device, such as a keyboard, a mouse, an electronic pen, a gesture based input device that may be active or passive, and/or a brain-computer interface.","It is to be noted that when a processor (computer) is disclosed in one embodiment, the scope of the embodiment is intended to also cover the use of multiple processors (computers).","Additionally, in some embodiments, a processor and/or computer disclosed in an embodiment may be part of the vehicle, while in other embodiments, the processor and/or computer may be separate of the vehicle.","For example, the processor and/or computer may be in a device carried by the occupant and/or remote of the vehicle (e.g., a server).","As used herein, references to “one embodiment” (and its variations) mean that the feature being referred to may be included in at least one embodiment of the invention.","Moreover, separate references to “one embodiment”, “some embodiments”, “another embodiment”, “still another embodiment”, etc., may refer to the same embodiment, may illustrate different aspects of an embodiment, and/or may refer to different embodiments.","Some embodiments may be described using the verb “indicating”, the adjective “indicative”, and/or using variations thereof.","Herein, sentences in the form of “X is indicative of Y” mean that X includes information correlated with Y, up to the case where X equals Y. Additionally, sentences in the form of “provide/receive an indication indicating whether X happened” refer herein to any indication method, including but not limited to: sending/receiving a signal when X happened and not sending/receiving a signal when X did not happen, not sending/receiving a signal when X happened and sending/receiving a signal when X did not happen, and/or sending/receiving a first signal when X happened and sending/receiving a second signal X did not happen.","Herein, “most” of something is defined herein as above 51% of the something (including 100% of the something).","A “portion” of something refers herein to 0.1% to 100% of the something (including 100% of the something).","Sentences of the form “a portion of an area” refer herein to 0.1% to 100% percent of the area.","As used herein, the terms “comprises,” “comprising,” “includes,” “including,” “has,” “having”, or any other variation thereof, indicate an open claim language that does not exclude additional limitations.","The “a” or “an” is employed to describe one or more, and the singular also includes the plural unless it is obvious that it is meant otherwise.","Certain features of some of the embodiments, which may have been, for clarity, described in the context of separate embodiments, may also be provided in various combinations in a single embodiment.","Conversely, various features of some of the embodiments, which may have been, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-combination.","Embodiments described in conjunction with specific examples are presented by way of example, and not limitation.","Moreover, it is evident that many alternatives, modifications, and variations will be apparent to those skilled in the art.","It is to be understood that other embodiments may be utilized and structural changes may be made without departing from the scope of the appended claims and their equivalents."]],"string":"[\n [\n \"Large mirror inside an autonomous vehicle\",\n \"A large mirroring element is located in front of an occupant who sits in a front seat of an autonomous on-road vehicle.\",\n \"The large mirroring element provides the effect of reflecting light arriving from the occupant's direction.\",\n \"Optionally, a camera takes video of the outside environment in front of the occupant, sends the video to a computer that generates a representation of the outside environment in front of the occupant at eye level, and a display located in front of the occupant presents the representation to the occupant.\"\n ],\n [\n \"1.An autonomous on-road vehicle providing the effect of a large front mirror, comprising: a compartment; and a mirroring element located in front of an occupant who sits in a front seat of the compartment; wherein the mirroring element captures at least 10×10 degrees of the occupant's forward field of view from the horizon to at least 10° below the horizon during normal driving, and provides an effect of reflecting more than 25% of the light arriving from the occupant's direction.\",\n \"2.The autonomous on-road vehicle of claim 1, wherein height and width of the mirroring element exceeds 50×40 cm, and the mirroring element captures above 30×30 degrees of the occupant's field of view, from the horizon to 30° below the horizon.\",\n \"3.The autonomous on-road vehicle of claim 1, wherein height and width of the mirroring element exceeds 25×25 cm, and the mirroring element captures more than 25% of the area where a conventional windshield of a normal non-autonomous road vehicle in year 2016 is expected to be located.\",\n \"4.The autonomous on-road vehicle of claim 1, wherein the mirroring element increases the volume of the vehicle compartment as perceived by the occupant due to the reflection effect, and the mirroring element provides an effect of reflecting more than at least one of 50%, 80%, and 90% of the light arriving from the occupant's direction.\",\n \"5.The autonomous on-road vehicle of claim 1, wherein the mirroring element comprises an optical mirror, and most of the effect of reflecting is generated by the optical mirror.\",\n \"6.The autonomous on-road vehicle of claim 1, wherein the mirroring element comprises a Fresnel type optical reflector comprising reflecting prisms; wherein the Fresnel type optical reflector is not flat, but the reflecting prisms are arranged in angles that reflect the light from the occupant such as to imitate an essentially flat mirror.\",\n \"7.The autonomous on-road vehicle of claim 1, wherein the effect of reflecting is achieved by a digital mirror; wherein the digital mirror comprises: multiple cameras embedded within the digital mirror and configured to take images of the occupant, and multiple light emitting pixels configured to emit light rays that generate the effect of reflecting.\",\n \"8.The autonomous on-road vehicle of claim 1, wherein the mirroring element comprises an electronic display, and further comprising at least one camera configured to take video of the occupant, and a computer configured to generate, based on the video of the occupant, video to be displayed by the electronic display in order to generate the effect of reflecting.\",\n \"9.The autonomous on-road vehicle of claim 8, wherein the at least one camera comprises first and second cameras, located to the right and left of the occupant, respectively.\",\n \"10.The autonomous on-road vehicle of claim 8, wherein the at least one camera comprises first and second cameras, located above the level of the occupant's nose and below the level of the occupant's collarbone, respectively, and less than 80 cm away from the occupant.\",\n \"11.The autonomous on-road vehicle of claim 8, further comprising a camera configured to take video of the outside environment in front of the occupant, and the computer is further configured to generate, based on the video, a representation of the outside environment in front of the occupant, at eye level, to be displayed by the mirroring element to the occupant.\",\n \"12.The autonomous on-road vehicle of claim 11, wherein the mirroring element is further configured to operate in a second state in which it: (i) provides the effect of reflecting less than 20% of the light arriving from the occupant's direction, and (ii) presents to the occupant the representation of the outside environment; whereby presenting the representation of the outside environment imitates a windshield to the outside environment.\",\n \"13.The autonomous on-road vehicle of claim 11, further comprising a user interface configured to enable the occupant to switch between seeing the effect of reflecting and seeing the representation of the outside environment.\",\n \"14.The autonomous on-road vehicle of claim 11, wherein the electronic display is comprised in a head-mounted display (HMD).\",\n \"15.The autonomous on-road vehicle of claim 11, wherein the electronic display is mechanically coupled to the compartment, and/or the mirroring element comprises the electronic display.\",\n \"16.An autonomous on-road vehicle providing the effect of a large front mirror, comprising: a compartment comprising a front seat; a camera, physically coupled to the vehicle, configured to take images of an occupant who sits in the front seat; a computer configured to generate, based on the images, a video that shows a mirror effect; a communication module configured to transmit the video to a head-mounted display (HMD) worn by the occupant; and the HMD is configured to present the video to the occupant, such that the occupant sees a representation of his or her reflection when looking forward at eye level.\",\n \"17.The autonomous on-road vehicle of claim 16, wherein the video presented to the occupant captures at least 30×30 degrees of the occupant's field of view, from the horizon to 30° below the horizon.\",\n \"18.The autonomous on-road vehicle of claim 16, further comprising a second camera configured to take a second set of images of the outside environment in front of the occupant, the computer is further configured to generate a representation of the outside environment based on the second set of images, and the HMD is configured to present the representation of the outside environment in addition to the video that shows the mirror effect.\",\n \"19.The autonomous on-road vehicle of claim 16, wherein the HMD is selected from the group comprising: a virtual reality headset, an augmented reality headset, and mixed reality headset; and wherein the camera comprises first and second cameras, located to the right and left of the occupant, respectively.\",\n \"20.The autonomous on-road vehicle of claim 16, wherein the camera comprises first and second cameras, located above the level of the occupant's nose and below the level of the occupant's collarbone, respectively, and less than 80 cm away from the occupant.\"\n ],\n [\n \" BACKGROUND Windowless vehicles, or vehicles without a windshield, may have various benefits when it comes to safety, weight, and cost.\",\n \"However, in some cases, some occupants may feel claustrophobic in such a vehicle.\",\n \"Thus, there is a need for a way to make traveling in such vehicles more pleasurable for occupants who might feel somewhat unease in confined spaces.\",\n \"Other occupants would like to see themselves while traveling.\",\n \"Thus, there is a need to have a large front mirror that enables the occupants to see themselves.\"\n ],\n [\n \" SUMMARY Some aspects of this disclosure involve an autonomous on-road vehicle that provides the effect of a large front mirror.\",\n \"The vehicle includes a compartment having a large mirroring element located in front of an occupant who sits in a front seat of the compartment.\",\n \"The mirroring element captures a region corresponding to at least 10×10 degrees, including a region spanning from the horizon to at least 10° below the horizon of the occupant's forward field of view during normal driving.\",\n \"Additionally, the mirroring element provides an effect of reflecting more than 25% of the light arriving from the occupant's direction.\",\n \"In some embodiments, the vehicle has an advantage that it can increase the perceived compartment volume, which can make travelling in the vehicle more pleasurable for some people.\",\n \"Other aspects of this disclosure involve an autonomous on-road vehicle that provides the effect of a large front mirror.\",\n \"The vehicle includes a compartment, a camera, a computer, and a head-mounted display (HMD).\",\n \"The compartment includes a front seat, the camera is physically coupled to the vehicle and takes images of an occupant who sits in the front seat, the computer generates a video that shows a mirror effect based on the images, the communication module transmits the video to the HMD that is worn by the occupant, and the HMD presents the video to the occupant, such that the occupant sees a representation of his or her reflection when looking forward at eye level.\"\n ],\n [\n \"CROSS-REFERENCE TO RELATED APPLICATIONS This Application is a Continuation of U.S. application Ser.\",\n \"No.\",\n \"15/335,404, filed Oct. 26, 2016, which claims priority to U.S.\",\n \"Provisional Patent Application No.\",\n \"62/246,187, filed on 26 Oct. 2015, and U.S.\",\n \"Provisional Patent Application No.\",\n \"62/369,127, filed on 31 Jul.\",\n \"2016.ACKNOWLEDGMENTS Gil Thieberger would like to thank his holy and beloved teacher, Lama Dvora-hla, for her extraordinary teachings and manifestation of wisdom, love, compassion and morality, and for her endless efforts, support, and skills in guiding him and others on their paths to freedom and ultimate happiness.\",\n \"Gil would also like to thank his beloved parents for raising him exactly as they did.\",\n \"BACKGROUND Windowless vehicles, or vehicles without a windshield, may have various benefits when it comes to safety, weight, and cost.\",\n \"However, in some cases, some occupants may feel claustrophobic in such a vehicle.\",\n \"Thus, there is a need for a way to make traveling in such vehicles more pleasurable for occupants who might feel somewhat unease in confined spaces.\",\n \"Other occupants would like to see themselves while traveling.\",\n \"Thus, there is a need to have a large front mirror that enables the occupants to see themselves.\",\n \"SUMMARY Some aspects of this disclosure involve an autonomous on-road vehicle that provides the effect of a large front mirror.\",\n \"The vehicle includes a compartment having a large mirroring element located in front of an occupant who sits in a front seat of the compartment.\",\n \"The mirroring element captures a region corresponding to at least 10×10 degrees, including a region spanning from the horizon to at least 10° below the horizon of the occupant's forward field of view during normal driving.\",\n \"Additionally, the mirroring element provides an effect of reflecting more than 25% of the light arriving from the occupant's direction.\",\n \"In some embodiments, the vehicle has an advantage that it can increase the perceived compartment volume, which can make travelling in the vehicle more pleasurable for some people.\",\n \"Other aspects of this disclosure involve an autonomous on-road vehicle that provides the effect of a large front mirror.\",\n \"The vehicle includes a compartment, a camera, a computer, and a head-mounted display (HMD).\",\n \"The compartment includes a front seat, the camera is physically coupled to the vehicle and takes images of an occupant who sits in the front seat, the computer generates a video that shows a mirror effect based on the images, the communication module transmits the video to the HMD that is worn by the occupant, and the HMD presents the video to the occupant, such that the occupant sees a representation of his or her reflection when looking forward at eye level.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS The embodiments are herein described by way of example only, with reference to the accompanying drawings.\",\n \"No attempt is made to show structural details of the embodiments in more detail than is necessary for a fundamental understanding of the embodiments.\",\n \"In the drawings: FIG.\",\n \"1 is a schematic illustration of components of a system configured to combine video see-through (VST) with video-unrelated-to-the-VST (VUR); FIG.\",\n \"2 illustrates an HMD tracking module that measures the position of the HMD relative to the compartment; FIG.\",\n \"3 illustrates a vehicle in which an occupant wears an HMD; FIG.\",\n \"4 illustrates an occupant wearing an HMD and viewing large VUR and smaller VST; FIG.\",\n \"5a illustrates how the VST moves to the upper left when the occupant looks to the bottom right; FIG.\",\n \"5b illustrates how the VST moves to the bottom right when the occupant looks to the upper left; FIG.\",\n \"6 illustrates HMD-video that includes both a non-transparent VST and video that shows the hands of the occupant and the interior of the compartment; FIG.\",\n \"7 illustrates HMD-video that includes both a partially transparent VST and video that shows the hands of the occupant and the interior of the compartment; FIG.\",\n \"8 illustrates HMD-video that includes a VST and partially transparent video that shows the hands of the occupant and the interior of the compartment; FIG.\",\n \"9a illustrates HMD-video that includes a VUR in full FOV, a first window comprising compartment-video (CV) and a second smaller window comprising the VST; FIG.\",\n \"9b illustrates HMD-video that includes VUR in full FOV, a first window comprising the CV and a second partially transparent smaller window comprising the VST; FIG.\",\n \"10a illustrates HMD-video that includes VUR in full FOV, a first window comprising VST and a second smaller window comprising zoom out of the CV; FIG.\",\n \"10b illustrates HMD-video that includes VUR and a partially transparent CV; FIG.\",\n \"11a illustrates a FOV of a vehicle occupant when the occupant wears an HMD that presents HMD-video; FIG.\",\n \"11b illustrates a FOV of a vehicle occupant when the vehicle occupant does not wear an HMD that presents the video, such as when watching an autostereoscopic display; FIG.\",\n \"11c illustrates FOV of a 3D camera that is able to capture sharp images from different focal lengths; FIG.\",\n \"12 is a schematic illustration of components of a system configured to enable an HMD to cooperate with a window light shading module; FIG.\",\n \"13a illustrates a first mode for a shading module where an occupant sees the outside environment through the optical see-through component; FIG.\",\n \"13b illustrates a second mode for a shading module where the occupant sees the outside environment through a VST; FIG.\",\n \"14 illustrates a VST over a curtain; FIG.\",\n \"15 illustrates a light shading module that is unfurled on the inside of the compartment; FIG.\",\n \"16 illustrates a light shading module that is unfurled on the outside of the compartment; FIG.\",\n \"17 is a schematic illustration of components of a video system that may be used to increase awareness of an occupant of a vehicle regarding an imminent SDRS; FIG.\",\n \"18a illustrates presenting VUR to an occupant when there is no indication that an SDRS event is imminent; FIG.\",\n \"18b illustrates presenting VST responsive to receiving an indication that an SDRS event is imminent (a pothole); FIG.\",\n \"18c illustrates presenting VST responsive to receiving an indication that an SDRS event is imminent (a sharp turn); FIG.\",\n \"19a illustrates presenting VUR and VST when there is no indication that an SDRS event is imminent; FIG.\",\n \"19b illustrates presenting a larger VST responsive to receiving an indication that an SDRS event is imminent (a road bump); FIG.\",\n \"19c illustrates presenting a partially transparent VST responsive to receiving an indication that an SDRS event is imminent; FIG.\",\n \"20a illustrates a smart glass shading module when there is no indication that an SDRS event is imminent; FIG.\",\n \"20b illustrates the smart glass shading module when there is an indication that an SDRS event is imminent; FIG.\",\n \"21a and FIG.\",\n \"21b illustrate vehicles with an SAEDP in their compartment were an occupant uses an HMD to receive a representation of the outside environment; FIG.\",\n \"22 illustrates a vehicle with an SAEDP in the vehicle's compartment with displays; FIG.\",\n \"23 illustrates how an SAEDP protects the occupant in a side collision; FIG.\",\n \"24a and FIG.\",\n \"24b illustrate a vehicle with a motor configured to move a nontransparent SAEDP to cover a side window; FIG.\",\n \"25a and FIG.\",\n \"25b illustrate a vehicle with a motor configured to move a front SAEDP between first and second states; FIG.\",\n \"26a illustrates an SAEDP mounted to the front of a vehicle at eye level of an occupant of the vehicle; FIG.\",\n \"26b illustrates an outer SAEDP that includes two air bags; FIG.\",\n \"27a and FIG.\",\n \"27b illustrate a motorized external SAEDP that can move between first and second states multiple times; FIG.\",\n \"28 illustrates a vehicle compartment in which an occupant may lay down; FIG.\",\n \"29 illustrates a vehicle with a front mirror; FIG.\",\n \"30a illustrates one example of a configuration of a plurality of beams located in the left side of the vehicle; FIG.\",\n \"30b illustrates one example of a configuration of a plurality of beams located in the front of the vehicle; and FIG.\",\n \"31a and FIG.\",\n \"31b are schematic illustrations of computers able to realize one or more of the embodiments discussed herein.\",\n \"DETAILED DESCRIPTION The following are definitions of various terms that may be used to describe one or more of the embodiments in this disclosure.\",\n \"The terms “autonomous on-road vehicle” and “autonomous on-road manned vehicle” refer to cars and motorcycles designed to drive on public roadways utilizing automated driving of level 3 and above according to SAE International standard J3016 “Taxonomy and Definitions for Terms Related to On-Road Motor Vehicle Automated Driving Systems”.\",\n \"For example, the autonomous on-road vehicle may be a level 3 vehicle, in which within known, limited environments, drivers can safely turn their attention away from driving tasks; the autonomous on-road vehicle may be a level 4 vehicle, in which the automated system can control the vehicle in all but a few environments; and/or the autonomous on-road vehicle may be a level 5 vehicle, in which no human intervention is required and the automatic system can drive to any location where it is legal to drive.\",\n \"Herein, the terms “autonomous on-road vehicle” and “self-driving on-road vehicle” are equivalent terms that refer to the same.\",\n \"The term “autonomous on-road vehicle” does not include trains, airplanes, boats, and armored fighting vehicles.\",\n \"An autonomous on-road vehicle utilizes an autonomous-driving control system to drive the vehicle.\",\n \"The disclosed embodiments may use any suitable known and/or to be invented autonomous-driving control systems.\",\n \"The following three publications describe various autonomous-driving control systems that may be utilized with the disclosed embodiments: (i) Paden, Brian, et al.\",\n \"“A Survey of Motion Planning and Control Techniques for Self-driving Urban Vehicles.” arXiv preprint arXiv:1604.07446 (2016); (ii) Surden, Harry, and Mary-Anne Williams.\",\n \"“Technological Opacity, Predictability, and Self-Driving Cars.” Predictability, and Self-Driving Cars (Mar.\",\n \"14, 2016) (2016); and (iii) Gonzalez, David, et al.\",\n \"“A Review of Motion Planning Techniques for Automated Vehicles.” IEEE Transactions on Intelligent Transportation Systems 17.4 (2016): 1135-1145.Autonomous-driving control systems usually utilize algorithms such as machine learning, pattern recognition, neural network, machine vision, artificial intelligence, and/or probabilistic logic to calculate on the fly the probability of an imminent collision, or to calculate on the fly values that are indicative of the probability of an imminent collision (from which it is possible to estimate the probability of an imminent collision).\",\n \"The algorithms usually receive as inputs the trajectory of the vehicle, measured locations of at least one nearby vehicle, information about the road, and/or information about environmental conditions.\",\n \"Calculating the probability of an imminent collision is well known in the art, also for human driven vehicles, such as the anticipatory collision system disclosed in U.S. Pat.\",\n \"No.\",\n \"8,041,483 to Breed.\",\n \"In order to calculate whether a Sudden Decrease in Ride Smoothness (SDRS) event is imminent, the autonomous-driving control system may compare parameters describing the state of the vehicle at time t1 with parameters describing the state of the vehicle at time t2 that is shortly after t1.If the change in one or more of the parameters reaches a threshold (such as deceleration above a certain value, change of height in the road above a certain value, and/or an angular acceleration above a certain value) then it may be determined that an SDRS event is imminent.\",\n \"An “occupant” of a vehicle, as the term is used herein refers to a person that is in the vehicle when it drives.\",\n \"The term “occupant” refers to a typical person having a typical shape, such as a 170 cm tall human (herein “cm” refers to centimeters).\",\n \"An occupant may be a driver, having some responsibilities and/or control regarding the driving of the vehicle (e.g., in a vehicle that is not completely autonomous), or may be a passenger.\",\n \"When an embodiment refers to “the occupant of the vehicle”, it may refer to one of the occupants of the vehicle.\",\n \"Stating that a vehicle has an “occupant” should not be interpreted that the vehicle necessarily accommodates only one occupant at a time, unless that is explicitly stated, such as stating that the vehicle is “designed for a single occupant”.\",\n \"Herein, a “seat” may be any structure designed to hold an occupant travelling in the vehicle (e.g., in a sitting and/or reclining position).\",\n \"A “front seat” is a seat that positions an occupant it holds no farther from the front of the vehicle than any other occupants of the vehicle are positioned.\",\n \"Herein, sitting in a seat also refers to sitting on a seat.\",\n \"Sitting in a seat is to be interpreted in this disclosure as occupying the space corresponding the seat, even if the occupant does so by assuming a posture that does not necessarily correspond to sitting.\",\n \"For example, in some vehicles the occupant may be reclined or lying down, and in other vehicles the occupant may be more upright, such as when leaning into the seat in a half standing half seating position similar to leaning into a Locus Seat by Focal Upright LLC.\",\n \"The interchangeable terms “environment outside the vehicle” and “outside environment” refer to the environment outside the vehicle, which includes objects that are not inside the vehicle compartment, such as other vehicles, roads, pedestrians, trees, buildings, mountains, the sky, and outer space.\",\n \"A sensor “mounted to the vehicle” may be connected to any relevant part of the vehicle, whether inside the vehicle, outside the vehicle, to the front, back, top, bottom, and/or to a side of the vehicle.\",\n \"A sensor, as used herein, may also refer to a camera.\",\n \"The term “camera” refers herein to an image-capturing device that takes images of an environment.\",\n \"For example, the camera may be based on at least one of the following sensors: a CCD sensor, a CMOS sensor, a near infrared (NIR) sensor, an infrared sensor (IR), and a device based on active illumination such as a LiDAR.\",\n \"The term “video” refers to a series of images that may be provided in a fixed rate, variable rates, a fixed resolution, and/or dynamic resolutions.\",\n \"The use of a singular “camera” should be interpreted herein as “one or more cameras”.\",\n \"Thus, when embodiments herein are described as including a camera that captures video and/or images of the outside environment in order to generate a representation of the outside environment, the representation may in fact be generated based on images and/or video taken using multiple cameras.\",\n \"Various embodiments described herein involve providing an occupant of the vehicle with representation of the outside environment, generated by a computer and/or processor, based on video taken by a camera.\",\n \"In some embodiments, video from a single camera (e.g., which may be positioned on the exterior of the vehicle at eye level), may be sent to presentation to the occupant by the processor and/or computer following little, if any, processing.\",\n \"In other embodiments, video from a single camera or multiple cameras is processed in various ways, by the computer and/or processor, in order to generate the representation of the outside environment that is presented to the occupant.\",\n \"Methods and systems for stitching live video streams from multiple cameras, stitching live video streams with database objects and/or other video sources, transforming a video stream or a stitched video stream from one point of view to another point of view (such as for generating a representation of the outside environment for an occupant at eye level, or for generating a compartment view for a person standing outside the compartment), tracking the position of an HMD relative to a compartment, and presenting rendered images that are perfectly aligned with the outside world—are all known in the art of computer graphics, video stitching, image registration, and real-time 360° imaging systems.\",\n \"The following publications are just a few examples of reviews and references that describe various ways to perform the video stitching, image registration, tracking, and transformations, which may be utilized by the embodiments disclosed herein: (i) Wang, Xiaogang.\",\n \"“Intelligent multi-camera video surveillance: A review.” Pattern recognition letters 34.1 (2013): 3-19.\",\n \"(ii) Szeliski, Richard.\",\n \"“Image alignment and stitching: A tutorial.” Foundations and Trends® in Computer Graphics and Vision 2.1 (2006): 1-104.\",\n \"(iii) Tanimoto, Masayuki.\",\n \"“FTV: Free-viewpoint television.” Signal Processing: Image Communication 27.6 (2012): 555-570.\",\n \"(iv) Ernst, Johannes M., Hans-Ullrich Doehler, and Sven Schmerwitz.\",\n \"“A concept for a virtual flight deck shown on an HMD.” SPIE Defense+ Security.\",\n \"International Society for Optics and Photonics, 2016.\",\n \"(v) Doehler, H-U., Sven Schmerwitz, and Thomas Lueken.\",\n \"“Visual-conformal display format for helicopter guidance.” SPIE Defense+ Security.\",\n \"International Society for Optics and Photonics, 2014.\",\n \"(vi) Sanders-Reed, John N., Ken Bernier, and Jeff Güell “Enhanced and synthetic vision system (ESVS) flight demonstration.” SPIE Defense and Security Symposium.\",\n \"International Society for Optics and Photonics, 2008.And (vii) Bailey, Randall E., Kevin J. Shelton, and J. J. Arthur III.\",\n \"“Head-worn displays for NextGen.” SPIE Defense, Security, and Sensing.\",\n \"International Society for Optics and Photonics, 2011.A video that provides “representation of the outside environment” refers to a video that enables the average occupant, who is familiar with the outside environment, to recognize the location of the vehicle in the outside environment from watching the video.\",\n \"In one example, the average occupant is a healthy 30 years old human who is familiar with the outside environment, and the threshold for recognizing a video as a “representation of the outside environment” is at least 20 correct recognitions of the outside environment out of 30 tests.\",\n \"Herein, sentences such as “VST that represents a view of the outside environment from the point of view of the occupant”, or “VST representation of the outside environment, which could have been seen from the point of view of the occupant” refer to a video representing at least a portion of the outside environment, with a deviation of less than ±20 degrees from the occupant's point of view of the outside environment, and zoom in the range of 30% to 300% (assuming the occupant's unaided view is at 100% zoom level).\",\n \"The VST may be generated based on at least one of the following resources: a video of the outside environment that is taken in real-time, a video of the outside environment that was taken in the past and is played/processed according to the trajectory of the vehicle, a database of the outside environment that is utilized for rendering the VST according to the trajectory of the vehicle, and/or a video that is rendered as function of locations of physical objects identified in the outside environment using detection and ranging systems such as RADAR and/or LIDAR.\",\n \"Moreover, the term “video see-through (VST)” covers both direct representations of the outside environment, such as a video of the outside environment, and/or enriched video of the outside environment, such as captured video and/or rendered video of the outside environment presented together with one or more layers of virtual objects, as long as more than 20% of the average vehicle occupants, who are familiar with the outside environment, would be able to determine their location in the outside environment, while the vehicle travels, without using a map, and with a margin of error below 200 meters.\",\n \"However, it is noted that showing a map that indicates the location of the vehicle on the driving path (such as from the start to the destination) is not considered herein as equivalent to the VST, unless the map includes all of the following properties: the map shows images of the path, the images of the path capture at least 5 degrees of the occupant's FOV at eye level, and the images of the path reflect the dynamics of the vehicle and change in a similar manner to a video taken by a camera mounted to the vehicle and directed to the outside environment.\",\n \"Herein, “field of view (FOV) of the occupant to the outside environment” refers to the part of the outside environment that is visible to the occupant of a vehicle at a particular position and orientation in space.\",\n \"In one example, in order for an occupant-tracking module to calculate the FOV to the outside environment of an occupant sitting in a vehicle compartment, the occupant-tracking module determines the position and orientation of the occupant's head.\",\n \"In another example, in order for an occupant-tracking module to calculate the FOV of an occupant sitting in a vehicle compartment, the occupant-tracking module utilizes an eye tracker.\",\n \"It is noted that sentences such as “a three dimensional (3D) video see-through (VST) that represents a view of the outside environment, which could have been seen from the point of view of the occupant had the FOV not been obstructed by at least a portion of the nontransparent element” cover also just one or more portions of the FOV, and are to be interpreted as “a three dimensional (3D) video see-through (VST) that represents a view of at least a portion of the outside environment, which could have been seen from the point of view of the occupant had at least some of the FOV not been obstructed by at least a portion of the nontransparent element”.\",\n \"The term “display” refers herein to any device that provides a human user with visual images (e.g., text, pictures, and/or video).\",\n \"The images provided by the display may be two-dimensional or three-dimensional images.\",\n \"Some non-limiting examples of displays that may be used in embodiments described in this disclosure include: (i) screens and/or video displays of various devices (e.g., televisions, computer monitors, tablets, smartphones, or smartwatches), (ii) headset- or helmet-mounted displays such as augmented-reality systems (e.g., HoloLens), virtual-reality systems (e.g., Oculus rift, HTC Vive, or Samsung GearVR), and mixed-reality systems (e.g., Magic Leap), and (iii) image projection systems that project images on a occupant's retina, such as: Virtual Retinal Displays (VRD) that create images by scanning low power laser light directly onto the retina, or light-field technologies that transmit light rays directly into the eye.\",\n \"Various embodiments may include a reference to elements located at eye level.\",\n \"The “eye level” height is determined according to an average adult occupant for whom the vehicle was designed, who sits straight and looks to the horizon.\",\n \"Sentences in the form of “an element located at eye level of an occupant who sits in a vehicle” refer to the element and not to the occupant.\",\n \"The occupant is used in such sentences in the context of “eye level”, and thus claims containing such sentences do not require the existence of the occupant in order to construct the claim.\",\n \"Sentences such as “SAEDP located at eye level”, “stiff element located at eye level”, and “crumple zone located at eye level” refer to elements that are located at eye level, but may also extended to other levels, such as from sternum level to the roof level, from floor level to eye level, and/or from floor level to roof level.\",\n \"For example, an SAEDP located at an eye level can extend from sternum level to above the occupant's head, such that at least a portion of the SAEDP is located at the eye level.\",\n \"Herein, “normal driving” refers to typical driving conditions, which persist most of the time the vehicle is in motion.\",\n \"During normal driving the probability of a collision is below a threshold that when reached typically involves one or more of the following actions: deployment of safety devices that are not usually deployed (e.g., inflating airbags), taking evasive action to avoid a collision, and warning occupants of the vehicle about an imminent event that may cause a Sudden Decrease in Ride Smoothness (SDRS).\",\n \"A Shock-Absorbing Energy Dissipation Padding (SAEDP) is an element that may be used to cushion impact of a body during a collision or during SDRS events.\",\n \"Various types of SAEDPs may be used in embodiments described herein, such as passive materials, airbags, and pneumatic pads.\",\n \"Some examples of passive materials that may be used for the SAEDP in one or more of the disclosed embodiments include one or more of the following materials: CONFOR® foam by Trelleborg Applied Technology, Styrofoam by The Dow Chemical Company, Micro-Lattice Materials and/or Metallic Microlattices (such as by HRL Laboratories in collaboration with researchers at University of California and Caltech), non-Newtonian energy Absorbing materials (such as D3O® by D3O lab, and DEFLEXION™ by Dow Corning®), Sorbothane® by Sorbothane Incorporated, and padding that includes compression cells and/or shock absorbers of the Xenith LLC type (such as described in U.S. Pat.\",\n \"No.\",\n \"8,950,735 and US patent application num.\",\n \"20100186150), and materials that include rubber such as a sponge rubber.\",\n \"The term “stiff element” refers to a material having stiffness and impact resistance equal or greater than that of glazing materials for use in motor vehicles as defined in the following two standards: (i) “American National Standard for Safety Glazing Materials for Glazing Motor Vehicles and Motor Vehicle Equipment Operating on Land Highways-Safety Standard” ANSI/SAE Z26.1-1996, and (ii) The Society of Automotive Engineers (SAE) Recommended Practice J673, revised April 1993, “Automotive Safety Glasses” (SAE J673, rev.\",\n \"April 93).\",\n \"The term “stiff element” in the context of low speed vehicles refers to a material having stiffness and impact resistance equal or greater than that of glazing materials for use in low speed motor vehicles as defined in Federal Motor Vehicle Safety Standard 205—Glazing Materials (FMVSS 205), from 49 CFR Ch.\",\n \"V (10-1-04 Edition).\",\n \"The stiff element may be transparent (such as automotive laminated glass, or automotive tempered glass) or nontransparent (such as fiber-reinforced polymer, carbon fiber reinforced polymer, steel, or aluminum).\",\n \"Herein, a nontransparent element is defined as an element having Visible Light Transmittance (VLT) between 0% and 20%, which does not enable the occupant to recognize what lies on the other side of it.\",\n \"For example, a thick ground glass usually allows light to pass through it but does not let the occupant recognize the objects on the other side of it, unlike plain tinted glass that usually lets the occupant recognize the objects on the other side of it, even when it features VLT below 10%.\",\n \"The nontransparent element includes an opaque element having VLT of essentially 0% and includes a translucent element having VLT below 20%.\",\n \"VLT is defined as the amount of incident visible light that passes through the nontransparent element, where incident light is defined as the light that strikes the nontransparent element.\",\n \"VLT is also known as Luminous Transmittance of a lens, a light diffuser, or the like, and is defined herein as the ratio of the total transmitted light to the total incident light.\",\n \"The common clear vehicle windshield has a VLT of approximately 85%, although US Federal Motor Vehicle Safety Standard No.\",\n \"205 allows the VLT to be as low as 70%.\",\n \"Sentences such as “video unrelated to the VST (VUR)” mean that an average occupant would not recognize the video as a representation of the outside environment.\",\n \"In some embodiments, the content of the VUR does not change as function of the position of the occupant's head, which means that the point of view from which the occupant watches the VUR does not change essentially when the occupant's head moves.\",\n \"Herein, stabilization effects, image focusing, dynamic resolution, color corrections, and insignificant changes to less than 10% of the frame as function of the position of the occupant's head—are still considered as content that does not change as function of the position of the occupant's head.\",\n \"Examples of such content (common in the year 2016) include cinema movies, broadcast TV shows, standard web browsers, and Microsoft Office 2016 applications (such as Word, Excel and PowerPoint).\",\n \"Herein, a “crumple zone” refers to a structure designed to slow down inertia and absorb energy from impact during a traffic collision by controlled deformation.\",\n \"The controlled deformation absorbs some of the impact within the outer parts of the vehicle, rather than being directly transferred to the occupants, while also preventing intrusion into and/or deformation of the compartment.\",\n \"Crumple zone may be achieved by various configurations, such as one or more of the following exemplary configurations: (i) by controlled weakening of sacrificial outer parts of the vehicle, while strengthening and increasing the stiffness of the inner parts of the vehicle, such as by using more reinforcing beams and/or higher strength steels for the compartment; (ii) by mounting composite fiber honeycomb or carbon fiber honeycomb outside the compartment; (iii) by mounting an energy absorbing foam outside the compartment; and/or (iv) by mounting an impact attenuator that dissipates impact.\",\n \"In order to enable an occupant of a vehicle to view the outside environment, without needing to look out of a physical window, some aspects of this disclosure involve systems that combine video see-through (VST) with video-unrelated-to-the-VST (VUR).\",\n \"In one embodiment, a system configured to combine video see-through (VST) with video-unrelated-to-the-VST (VUR) includes a head-mounted display (HMD), a camera, an HMD tracking module and a computer.\",\n \"The HMD is configured to be worn by an occupant of a compartment of a moving vehicle and to present an HMD-video to the occupant.\",\n \"The camera, which is mounted to the vehicle, is configured to take video of the outside environment (Vout).\",\n \"The HMD tracking module is configured to calculate position of the HMD relative to the compartment, based on measurements of a sensor.\",\n \"The computer is configured to receive a location of a video see-through window (VSTW) in relation to the compartment, and to calculate, based on the position of the HMD relative to the compartment, a window-location for the VSTW on the HMD-video.\",\n \"Additionally, the computer is further configured to generate, based on the window-location and the Vout, the VST that represents a view of the outside environment from the point of view of the occupant.\",\n \"The computer is also configured to generate the HMD-video based on combining the VUR with the VST in the window-location.\",\n \"It is to be noted that the content of the VUR is unrelated to the video taken by the camera.\",\n \"In one embodiment, a system configured to combine video see-through (VST) with video-unrelated-to-the-VST (VUR) includes at least the following components: a head-mounted display (HMD), such as HMD 15, a camera (e.g., camera 12), an HMD tracking module 27, and a computer 13.FIG.\",\n \"1 provides a schematic illustration of at least some of the relationships between the components mentioned above.\",\n \"The HMD 15 is configured to be worn by an occupant of a compartment of a moving vehicle and to present an HMD-video 16 to the occupant.\",\n \"In one embodiment, the HMD 15 is an augmented-reality (AR) HMD.\",\n \"In another embodiment, the HMD 15 is a virtual reality (VR) HMD.\",\n \"Optionally, in this embodiment, the system further comprises a video camera mounted to the VR HMD, and the VST video comprises video of the compartment received from the video camera mounted to the VR HMD.\",\n \"In yet another embodiment, the HMD 15 is a mixed reality HMD.\",\n \"The term “Mixed Reality” (MR) as used herein involves a system that is able to combine real world data with virtual data.\",\n \"Mixed Reality encompasses Augmented Reality and encompasses Virtual Reality that does not immerse its user 100% of the time in the virtual world.\",\n \"Examples of mixed reality HMDs include, but are not limited to, Microsoft HoloLens HMD and MagicLeap HMD.\",\n \"The camera 12, which is mounted to the vehicle, is configured to take video of the outside environment (Vout).\",\n \"Optionally, the data captured by the camera comprises 3D data.\",\n \"For example, the camera may be based on at least one of the following sensors: a CCD sensor, a CMOS sensor, a near infrared (NIR) sensor, an infrared sensor (IR), and a device based on active illumination such as a LiDAR.\",\n \"The HMD tracking module 27 is configured to calculate position of the HMD 15 relative to the compartment, based on measurements of a sensor.\",\n \"In different embodiments, the HMD tracking module 27 may have different configurations.\",\n \"In one embodiment, the sensor comprises first and second Inertial Measurement Units (IMUs).\",\n \"In this embodiment, the first IMU is physically coupled to the HMD 15 and is configured to measure a position of the HMD 15, and the second IMU is physically coupled to the compartment and is configured to measure a position of the compartment.\",\n \"The HMD tracking module 27 is configured to calculate the position of the HMD 15 in relation to the compartment based on the measurements of the first and second IMUs.\",\n \"In another embodiment, the sensor comprises an Inertial Measurement Unit (IMU) and a location measurement system.\",\n \"In this embodiment, the IMU is physically coupled to the HMD 15 and is configured to measure an orientation of the HMD 15.The location measurement system is physically coupled to the compartment and is configured to measure a location of the HMD in relation to the compartment.\",\n \"The HMD tracking module 27 is configured to calculate the position of the HMD 15 in relation to the compartment based on the measurements of the IMU and the location measurement system.\",\n \"Optionally, the location measurement system measures the location of the HMD 15 in relation to the compartment based on at least one of the following inputs: a video received from a camera that captures the HMD 15, a video received from a stereo vision system, measurements of magnetic fields inside the compartment, wireless triangulation measurements, acoustic positioning measurements, and measurements of an indoor positioning systems.\",\n \"FIG.\",\n \"2 illustrates one embodiment in which the HMD tracking module 27 is physically coupled to the compartment and is configured to measure the position of the HMD relative to the compartment.\",\n \"The HMD tracking module 27 may utilize a passive camera system, an active camera system that captures reflections of a projected grid, and/or a real-time locating systems based on microwaves and/or radio waves.\",\n \"The computer 13 is configured to receive a location of a video see-through window (VSTW) in relation to the compartment, and to calculate, based on the position of the HMD relative to the compartment, a window-location for the VSTW on the HMD-video.\",\n \"The computer 13 is also configured to generate, based on the window-location and the Vout, the VST that represents a view of the outside environment from the point of view of the occupant.\",\n \"Optionally, the VST is rendered as a 3D video content.\",\n \"Additionally, the computer 13 is further configured to generate the HMD-video 16 based on combining the VUR with the VST in the window-location.\",\n \"The computer 13 may use various know in the art computer graphics functions and/or libraries to generate the VST, transform the VST to the occupant's point of view, render the 3D video content, and/or combine the VUR with the VST.\",\n \"In one embodiment, the content of the VUR does not change when the occupant moves the head, and the content of the VUR is unrelated to the video taken by the camera.\",\n \"Additionally, the content of the VUR is generated based on data that was received more than 2 seconds before the HMD-video 16 is displayed to the occupant.\",\n \"Some examples of the VUR include a video stream of at least one of the following types of content: a recorded television show, a computer game, an e-mail, and a virtual computer desktop.\",\n \"FIG.\",\n \"3 illustrates one embodiment in which the occupant 14 wears an HMD 15.The HMD 15 provides video to the occupant 14 through the display of the HMD 15.The vehicle includes a camera 12 that takes video of the outside environment 11a and processes it in a manner suitable for the location of the occupant.\",\n \"The processed video is provided to the occupant's display in the HMD 15 as a VSTW and the position of the VSTW is calculated in relation to the compartment of the vehicle and moves with the compartment.\",\n \"While the vehicle is in motion, the VSTW change its content to represent the outside environment 11a of the vehicle.\",\n \"Whereas the video-unrelated-to-the-VST doesn't change when the occupant moves his head.\",\n \"The computer is configured to receive a location of a VSTW in relation to the compartment, and to calculate, based on the position of the occupant's head, a window-location for the VSTW on the video.\",\n \"FIG.\",\n \"4 illustrates one embodiment in which the occupant 44 wears HMD 45 and views large VUR 40 and smaller VST 41a.\",\n \"The VUR 40 does not change when the occupant's head 44 moves.\",\n \"The VSTW presents video of the street based on video taken by the camera that is mounted to the vehicle.\",\n \"The location of the video-see-through window in relation to the compartment does not change when the occupant 44 moves his/her head in order to imitate a physical window that does not change its position relative to the compartment when the occupant's head moves.\",\n \"FIG.\",\n \"5a illustrates how, in one embodiment, the VST moves to the upper left when the occupant 44 looks to the bottom right.\",\n \"FIG.\",\n \"5b illustrates how the VST moves to the bottom right when the occupant 44 looks to the upper left, while the VUR moves with the head.\",\n \"In both cases, the VUR moves with the head while the location of the VST changes according to the movement of the head relative to the compartment as measured by the HMD tracking module 27.In some embodiments, the content of the VUR may be augmented-reality content, mixed-reality content, and/or virtual-reality content rendered to correspond to the occupant's viewing direction.\",\n \"In this embodiment, the VUR is unrelated to the video taken by the camera.\",\n \"In one example, the VUR may include a video description of a virtual world in which the occupant may be playing a game (e.g., represented by an avatar).\",\n \"Optionally, in this example, most of the features of the virtual world are different from the view of the outside of the vehicle (as seen from the occupant's viewing direction).\",\n \"For example, the occupant may be driving in a city, while the virtual world displays woods, a meadow, or outer space.\",\n \"In another example, the VUR may include augmented reality content overlaid above a view of the inside of the compartment.\",\n \"In addition to the components described above, in some embodiments, the system may include a second camera that is mounted to the HMD and is configured to take video of the compartment (Vcomp).\",\n \"In this embodiment, the computer is further configured to generate a compartment-video (CV), based on Vcomp and a location of a compartment-video window (CVW) in relation to the HMD-video (e.g., HMD-video 16), and to generate the HMD-video also based on the CV in the CVW, such that the HMD-video combines the VUR with the VST in the window-location and with the CV in the CVW.\",\n \"There are various ways in which the CVW may be incorporated into the HMD-video.\",\n \"Some examples of these approaches are illustrated in the following figures.\",\n \"FIG.\",\n \"6 illustrates HMD-video that includes both a non-transparent VST 55 in the window-location and a CV 56 that shows the hands of the occupant and the interior of the compartment in the CVW.\",\n \"FIG.\",\n \"7 illustrates HMD-video that includes both a partially transparent VST 57 in the window-location and the CV 56 that shows the hands of the occupant and the interior of the compartment in the CVW.\",\n \"FIG.\",\n \"8 illustrates HMD-video that includes a VST 58 and partially transparent CV 59.The figure illustrates that the occupant sees the outside environment in full field-of-view (FOV), while on top of it there is a partially transparent image (illustrated as dotted image) of the compartment and the hands of the occupant, in order to help the occupant not to hit things in the compartment.\",\n \"FIG.\",\n \"9a illustrates HMD-video that includes a VUR 70 in full FOV, a first window comprising the CV 71 in the CVW and a second smaller window comprising the VST 72 in the window-location.\",\n \"FIG.\",\n \"9b illustrates HMD-video that includes VUR 70 in full FOV, a first window comprising the CV 71 in the CVW and a second partially transparent smaller window comprising the VST 73 in the window-location.\",\n \"FIG.\",\n \"10a illustrates HMD-video that includes VUR 70 in full FOV, a first window comprising VST 75 in the window-location and a second smaller window comprising zoom out of the CV 76 in the CVW.\",\n \"Optionally, the cabin view in the zoom out is smaller than in reality, and may enable the occupant to orient in the cabin.\",\n \"Optionally, the occupant may move the CVW, as illustrated in FIG.\",\n \"10a where the zoom out of the CV in the CVW is somewhat above its location in reality.\",\n \"FIG.\",\n \"10b illustrates HMD-video that includes VUR 70 and a partially transparent CV 72.Here a first occupant sees the VUR in full field-of-view (FOV), and on top of it there is a partially transparent image of the compartment and a second occupant that sits to the left of the first occupant, which may help the first occupant not to hit the second occupant.\",\n \"There may be various ways in which the system determines the location and/or size of the VSTW.\",\n \"In one embodiment, the VSTW is pinned to at least one of the following locations: a specific physical location and a location of an object in the compartment, such that the location of the VSTW in relation to the compartment does not change when the occupant moves his/her head with the HMD 15 as part of watching the HMD-video 16 and without commanding the VSTW to move in relation to the compartment.\",\n \"In another embodiment, the system includes a user interface configured to receive a command from the occupant to move and/or resize the VSTW in relation to the compartment.\",\n \"In one example, the command is issued through a voice command (e.g., saying “move VST to the bottom”).\",\n \"In another example, the command may be issued by making a gesture, which is detected by a gesture control module in the compartment and/or on a device of the occupant (e.g., as part of the HMD).\",\n \"Optionally, in this embodiment, the computer is further configured to: update the window-location based on the command from the occupant, and generate an updated VST based on the updated window-location and the video taken by the camera.\",\n \"In this embodiment, the VST and the updated VST present different VSTW locations and/or dimensions in relation to the compartment.\",\n \"Optionally, the HMD is configured not to present any part of the VST to the occupant when the window-location is not in the field of view presented to the occupant through the HMD.\",\n \"In yet another embodiment, the system may further include a video analyzer configured to identify an Object Of Interest (OOI) in the outside environment.\",\n \"For example, the OOI of interest may be a certain landmark (e.g., a building), a certain object (e.g., a store or a certain model of automobile), or a person.\",\n \"In this embodiment, the computer is further configured to receive, from the video analyzer, an indication of the position of the OOI, and to track the OOI by adjusting the window-location according to the movements of the vehicle, such that the OOI is visible via the VST.\",\n \"Optionally, the HMD is configured not to present any part of the VST to the occupant when the window-location is not in the field of view presented to the occupant through the HMD.\",\n \"The VST that represents the view of the outside environment from the point of view of the occupant, in some embodiments, does not necessarily match the video taken by the cameras.\",\n \"In one embodiment, the VST may utilize image enhancement techniques to compensate for outside lighting conditions, to give an occupant an experience similar to looking out through a conventional vehicle window but without the view being distorted by raindrops or dirt on the window, and/or to improve the visual impression of the outside environment e.g.\",\n \"by showing background images which are different from those retrievable from the outside environment.\",\n \"Additionally or alternatively, the VST may mimic the outside environment, alter the outside environment, and/or be completely different from what can be seen on the outside environment.\",\n \"The VST may be focused on providing visual information that makes the travelling more fun.\",\n \"The vehicle may provide different styles of the outside environment to different occupants in the vehicle, such that a first VST provided to a first occupant may mimic the outside environment, while a second VST provided to a second occupant may alter the outside environment and/or be completely different from the outside environment, optionally for comfort enhancement and/or entertainment.\",\n \"In some embodiments, the VST is informative, and aids at least some of the occupants to determine the location of the vehicle in the environment.\",\n \"In one embodiment, at least some of those occupants could not determine their location without the VST.\",\n \"In one example, less than 20% of average vehicle occupants, who are familiar with the outside environment, are able to determine their real location in the outside environment by watching the VUR, without using a map, with a margin of error that is less than 100 meters, and while the vehicle travels; while more than 20% of the average vehicle occupants, who are familiar with the outside environment, are able to determine their real location in the outside environment by watching the VST, without using a map, and with a margin of error that is less than 100 meters, and while the vehicle travels.\",\n \"FIG.\",\n \"11a illustrates a FOV in the context of presented video and terminology used herein.\",\n \"The vehicle occupant 200 wears an HMD 201 that presents HMD-video (such as HMD-video 16).\",\n \"The HMD-video may be presented at a single focal plane, or at multiple focal planes, depending on the characteristics of the HMD 201 (when the occupant focuses on a certain focal plane, then his/her point of gaze is said to be on the certain focal plane).\",\n \"In addition, the presented objects may be two-dimensional (2D) virtual objects and/or three-dimensional (3D) virtual objects that may also be referred to as holographic objects.\",\n \"Element 204 represents the location of a nontransparent element fixed to the vehicle compartment.\",\n \"In one example, the HMD 201 is a holographic HMD, such as Microsoft HoloLens, which can present content displayed on a series of focal planes that are separated by some distance.\",\n \"The virtual objects may be presented before the nontransparent element (e.g., polygons 202, 203), essentially on the nontransparent element 204, and/or beyond the nontransparent element (e.g., polygons 205, 206).\",\n \"As a result, the occupant's gaze distance may be shorter than the distance to the nontransparent element (e.g., distance to polygons 202, 203), essentially equal to the distance to the nontransparent element 204, and/or longer than the distance to the nontransparent element (e.g., distance to polygons 205, 206).\",\n \"Polygon 207 represents a portion of the presented video at eye level of the vehicle occupant, which in one example is within ±7 degrees from the horizontal line of sight.\",\n \"Although the figure illustrates overlapping FOVs of polygons 202, 203, 204, and 205, the HMD may show different objects, capturing different FOVs, at different focal planes.\",\n \"In one example, the HMD may project an image throughout a portion of, or all of, a display volume.\",\n \"Further, a single object such as a vehicle could occupy multiple volumes of space.\",\n \"According to the terminology used herein, the nontransparent element 204 is said to be located on FOV overlapping the FOV of polygons 205 and 203 because polygons 203, 204, 205 share the same FOV.\",\n \"FOV of polygon 206 is contained in the FOV of polygon 204, and FOV of polygon 207 intersects the FOV of polygon 204.FOV of polygon 203 is before the nontransparent element 204 and therefore may hide the nontransparent element 204 partially or entirely, especially when utilizing a multi-focal plane HMD.\",\n \"FIG.\",\n \"11b illustrates a FOV in the context of the presented video, where the vehicle occupant 210 does not wear an HMD that presents the video, such as when watching an autostereoscopic display.\",\n \"The autostereoscopic display is physically located on plane 214 and the presented video may be presented at a single focal plane, or at multiple focal planes, depending on the characteristics of the autostereoscopic display.\",\n \"In one example, the autostereoscopic display is a holographic display, such as SeeReal Technologies holographic display, where the presented video may present virtual objects before the focal plane of the autostereoscopic display (e.g., planes 212, 213), essentially on the focal plane of the autostereoscopic display 214, and/or beyond the focal plane of the autostereoscopic display (e.g., planes 215, 216).\",\n \"As a result, the occupant's gaze distance may be shorter than the distance to the autostereoscopic display (e.g., planes 212, 213), essentially equal to the distance to the autostereoscopic display 214, and/or longer than the distance to the autostereoscopic display (e.g., planes 215, 216).\",\n \"The term “autostereoscopic” includes technologies such as automultiscopic, glasses-free 3D, glassesless 3D, parallax barrier, integral photography, lenticular arrays, Compressive Light Field Displays, holographic display based on eye tracking, color filter pattern autostereoscopic display, volumetric display that reconstructs light field, integral imaging that uses a fly's-eye lens array, and/or High-Rank 3D (HR3D).\",\n \"FIG.\",\n \"11c illustrates FOV of a 3D camera that is able to capture sharp images from different focal lengths.\",\n \"In some embodiments, the vehicle and/or the HMD utilize at least one Inertial Measurement Unit (IMU), and the system utilizes an Inertial Navigation System (INS) to compensate imperfections in the IMU measurements.\",\n \"An INS typically has one or more secondary navigation sensors that provide direct measurements of the linear velocity, position and/or orientation of the vehicle.\",\n \"These secondary navigation sensors could be anything from stereo vision systems, to GPS receivers, to digital magnetic compasses (DMCs) or any other type of sensor that could be used to measure linear velocity, position and/or orientation.\",\n \"In one example, the information from these secondary navigation sensors is incorporated into the INS using an Extended Kalman Filter (EKF).\",\n \"The EKF produces corrections that are used to adjust the initial estimations of linear velocity, position and orientation that are calculated from the imperfect IMU measurements.\",\n \"Adding secondary navigation sensors into an INS can increase its ability to produce accurate estimations of the linear velocity, position and orientation of the vehicle over long periods of time.\",\n \"In one embodiment, the system utilizes domain specific assumptions in order to reduce drift of an INS used to calculate the HMD spatial position in relation to the compartment.\",\n \"More specifically, the following methods may be used to reduce or correct drift.\",\n \"Such methods generally fall in the categories of using sensor fusion and/or domain specific assumptions.\",\n \"(i) Sensor fusion refers to processes in which signals from two or more types of sensors are used to update and/or maintain the state of a system.\",\n \"In the case of INS, the state generally includes the orientation, velocity and displacement of the device measured in a global frame of reference.\",\n \"A sensor fusion algorithm may maintain this state using IMU accelerometer and gyroscope signals together with signals from additional sensors or sensor systems.\",\n \"There are many techniques to perform sensor fusion, such as Kalman filter and particle filter.\",\n \"One example of periodically correcting drift is to use position data from a triangulation positioning system relative to the compartment.\",\n \"Such systems try to combine the drift free nature of positions obtained from the triangulation positioning system with the high sampling frequency of the accelerometers and gyroscopes of the IMU.\",\n \"Roughly speaking, the accelerometer and gyroscope signals are used to ‘fill in the gaps’ between successive updates from the triangulation positioning system.\",\n \"Another example of reducing the drift is using a vector magnetometer that measures magnetic field strength in a given direction.\",\n \"The IMU may contain three orthogonal magnetometers in addition to the orthogonal gyroscopes and accelerometers.\",\n \"The magnetometers measure the strength and direction of the local magnetic field, allowing the north direction to be found.\",\n \"(ii) In some embodiments, it is possible to make domain specific assumptions about the movements of the occupant and/or the vehicle.\",\n \"Such assumptions can be used to minimize drift.\",\n \"One example in which domain specific assumptions may be exploited is the assumption that when the vehicle accelerates or decelerates significantly, the HMD accelerates or decelerates essentially the same as the vehicle, allowing HMD drift in velocity to be periodically corrected based on a more accurate velocity received from the autonomous-driving control system of the vehicle.\",\n \"Another example in which domain specific assumptions may be exploited is the assumption that when the vehicle accelerates or decelerates significantly, the HMDs of two occupants travelling in the same vehicle accelerate or decelerate essentially the same, allowing HMD drifts to be periodically corrected based on comparing the readings of the two HMDs.\",\n \"Still another example in which domain specific assumptions are exploited is the assumption that the possible movement of an HMD of a belted occupant is most of the time limited to a portion of the compartment, allowing HMD drifts to be periodically corrected based on identifying when the HMD exceeds beyond that portion of the compartment.\",\n \"In one example, it may be desirable to adjust the position of displaying a virtual object in response to relative motion between the vehicle and the HMD so that the virtual object would appear stationary in location.\",\n \"However, the HMD IMU may indicate that the HMD is moving even when the detected motion is a motion of the vehicle carrying the HMD.\",\n \"In order to distinguish between motion of the HMD caused by the vehicle and motion of the HMD relative to the vehicle, non-HMD sensor data may be obtained by the HMD from sensor such as an IMU located in the vehicle and/or the GPS system of the vehicle, and the motion of the vehicle may be subtracted from the motion of the HMD in order to obtain a representation of the motion of the HMD relative to the vehicle.\",\n \"By differentiating movements of the HMD caused by the occupant motion compared to movements caused by the vehicle motion, the rendering of the virtual object may be adjusted for the relative motion between the HMD and the vehicle.\",\n \"Using the nontransparent element, instead of a transparent glass window that provides the same FOV to the outside environment, may provide various benefits, such as: (i) reduced manufacturing cost of the vehicle compared to a similar vehicle having instead of the nontransparent element a transparent glass window that provides the same FOV to the outside environment as provided by the 3D display device, (ii) reduced weight of the vehicle compared to a similar vehicle having instead of the nontransparent element a transparent glass window that provides the same FOV to the outside environment as provided by the 3D display device, and provides the same safety level, (iii) better aerodynamic shape and lower drag for the vehicle, which results in an improved energy consumption, and (iv) improved privacy for the occupant as a result of not enabling an unauthorized person standing nearby the vehicle to see the occupant directly.\",\n \"The term “real-depth VST window (VSTW)” is defined herein as an imaging display that shows a 3D image of an outside environment located beyond a wall that interrupts the occupant's unaided view of the outside environment.\",\n \"The real-depth VSTW has the following characteristics: (i) the 3D image corresponds to a FOV to the outside environment beyond the wall, as would have essentially been seen by the occupant had the wall been removed; (ii) the outside environment is captured by a camera, and the rendering of the 3D image is based on images taken by the camera; and (iii) while looking via the imaging display, the occupant's point of gaze (where one is looking) is most of the time beyond the wall that interrupts the occupant's unaided view of the outside environment.\",\n \"A possible test to determine whether “(i) the 3D image corresponds to a FOV to the outside environment beyond the wall, as would have essentially been seen by the occupant had the wall been removed” is whether an imaginary user standing beyond the wall, watching both the real-depth VSTW and the outside environment, would recognize that at least 20% of the contours of objects in the 3D image correspond to the contours of the objects seen on the outside environment.\",\n \"Differences between the colors of the corresponding objects in the 3D image and the outside environment usually do not affect the criterion of the 20% corresponding contours, as long as the color difference does not affect the perception of the type of object.\",\n \"For example, different skin colors to corresponding people in the 3D image and the outside environment do not violate the criterion of the 20% corresponding contours.\",\n \"As another example, differences in the weight and/or height of corresponding objects in the 3D image and the outside environment do not violate the criterion of the 20% corresponding contours as long as the imaginary user understands that the objects correspond to the same person.\",\n \"Sentences such as “from the FOV of the occupant” are to be interpreted as no more than 20 degrees angular deviation from the field of view of the occupant to the outside environment.\",\n \"Zoom in/out does not affect the FOV as long as the average occupant would still recognize the rendered environment as the 3D VST.\",\n \"For example, zoom in of up to ×4, which maintains no more than 20 degrees angular deviation from the FOV of the occupant to the outside environment, is still considered “from the FOV of the occupant”.\",\n \"Reasonable lateral deviation essentially does not affect the FOV as long as the average occupant would still recognize the rendered environment as the 3D VST.\",\n \"For example, displaying to the occupant the outside environment from the FOV of a camera located on the roof of the occupant's vehicle, is still considered as showing the outside environment from the occupant's FOV.\",\n \"A possible test to determine whether “(ii) the outside environment is measured by a camera, and the images taken by the camera are used to render the 3D image” is whether the real-depth VSTW would display a different 3D VST when it does not receive the images taken by the camera.\",\n \"For example, assuming the camera is a 3D video camera, and the 3D image is a manipulation of the images taken by the 3D video camera; then, when the real-depth VSTW does not receive the images, it cannot show the changes that are taking place in the outside environment.\",\n \"As another example, assuming the 3D image is mainly rendered from cached data stored in a database, and the camera is used to provide the setup of objects that behave in an unknown way, such as trajectories of nearby vehicles on the road, or a gesture of a person walking beyond the wall; then, when the output of the camera is used to render the 3D image, the real-depth VSTW would represent the unknown trajectory of the nearby vehicles or the unknown gesture of the person, while when the output of the camera is not used to render the 3D image, the real-depth VSTW would not represent the unknown trajectory of the nearby vehicles or the unknown gesture of the person merely because the renderer does not have that data.\",\n \"A possible test to determine whether “(iii) the occupant's point of gaze (where one is looking) is most of the time beyond the wall that interrupts the occupant's unaided view of the outside environment” includes the following steps: (a) use eye tracker to determine the point of gaze on a representative scenario, (b) measure the distance to the wall, and (c) determine whether the average gaze distance is longer than the distance to the wall.\",\n \"Some aspects of this disclosure involve a system that utilizes window shading of a vehicle window in order to improve the quality of video viewed by an occupant of the vehicle who wears a head-mounted display (HMD).\",\n \"In one embodiment, an autonomous on-road vehicle includes a system configured to enable an HMD to cooperate with a window light shading module.\",\n \"This embodiment involves a light shading module, a camera, a processor, and the HMD.\",\n \"The light shading module is integrated with a vehicle window and is configured to be in at least one of first and second states.\",\n \"In the first state the Visible Light Transmittance (VLT) of the vehicle window is above 10% of ambient light entering through the window, in the second state the VLT of the vehicle window is below 50% of ambient light entering through the window, and the VLT of the vehicle window in the first state is higher than the VLT of the vehicle window in the second state.\",\n \"The camera is fixed to the vehicle and configured to take video of the outside environment.\",\n \"The processor is configured to generate, based on the video, a video see-through (VST) that represents the outside environment from a point of view of an occupant looking to the outside environment through at least a portion of the vehicle window.\",\n \"The HMD comprises an optical see-through component and a display component; the HMD is configured to operate according to a first mode of operation when the occupant looks at the direction of the vehicle window and the light shading module is in the first state, and to operate according to a second mode of operation when the occupant looks at the direction of the vehicle window and the light shading module is in the second state.\",\n \"Wherein the total intensity of the VST light, emitted by the display component and reaching the occupant's eyes, is higher in the second mode than in the first mode.\",\n \"In one embodiment, a system configured to enable a head-mounted display (HMD) to cooperate with a window light shading module of an autonomous on-road vehicle includes at least the following elements: the HMD 62, a light shading module 61, a camera (such as camera 12), and a processor 18.FIG.\",\n \"12 is a schematic illustration of at least some of the relationships between the system elements mentioned above.\",\n \"The light shading module 61 is integrated with a vehicle window and is configured to be in at least one of first and second states.\",\n \"Optionally, the light shading module 61 covers more than half of the front windshield in the second state.\",\n \"In one embodiment, in the first state, the Visible Light Transmittance (VLT) of the vehicle window is above 10% of ambient light entering through the window, and in the second state, the VLT of the vehicle window is below 50% of ambient light entering through the window.\",\n \"Additionally, the VLT of the vehicle window in the first state is higher than the VLT of the vehicle window in the second state.\",\n \"In another embodiment, in the first state the VLT of the vehicle window is above 70% of ambient light entering through the window, and in the second state, the VLT of the vehicle window is below 30% of ambient light entering through the window.\",\n \"Herein, “ambient light” in the context of a vehicle refers to visible light that is not controlled by the vehicle, such as light arriving from: the sun, lights of other vehicles, street/road lighting, and various reflections from elements such as windows.\",\n \"In some embodiments, utilizing the light shading module 61 may improve the quality of images viewed via the HMD 62 when the light shading module 61 is in the second state.\",\n \"Optionally, the perceived contrast of the optical see-through component is better when the light shading module is in the second state compared to when the light shading module 61 is in the first state.\",\n \"Various types of light shading modules may be utilized in embodiments described herein.\",\n \"In one embodiment, the light shading module 61 is a movable physical element configured to reduce the intensity of the ambient light entering into the vehicle compartment through the vehicle window.\",\n \"Optionally, the light shading module is unfurled on the inside of the compartment in order to block at least 50% of the ambient light intensity.\",\n \"Optionally, the light shading module is unfurled on the outside of the compartment in order to block at least 50% of the ambient light intensity.\",\n \"FIG.\",\n \"13a illustrates a first mode where the occupant sees the outside environment through the optical see-through component.\",\n \"This figure illustrates the view that the occupant sees when looking outside through the window.\",\n \"FIG.\",\n \"13b illustrates a second mode where the occupant sees the outside environment through the VST.\",\n \"In this example, the outside environment is a bit different, and there is also a virtual Superman floating near the tree.\",\n \"In another embodiment, the light shading module 61 may be a curtain.\",\n \"FIG.\",\n \"14 illustrates a VST over a curtain.\",\n \"FIG.\",\n \"15 illustrates a light shading module that is unfurled on the inside of the compartment.\",\n \"FIG.\",\n \"16 illustrates a light shading module that is unfurled on the outside of the compartment.\",\n \"And in yet another embodiment, the vehicle window is made of a material that is able to serve as the light shading module 61 by changing its transparency properties.\",\n \"The camera is fixed to the vehicle, and configured to take video of the outside environment.\",\n \"For example, the camera may be based on at least one of the following sensors: a CCD sensor, a CMOS sensor, a near infrared (NIR) sensor, an infrared sensor (IR), and a device based on active illumination such as a LiDAR.\",\n \"The processor is configured to generate, based on the video, a video see-through (VST 19) that represents the outside environment from a point of view of an occupant looking to the outside environment through at least a portion of the vehicle window.\",\n \"Optionally, the processor is further configured not to generate the VST 19 when the HMD 62 operates in the first mode.\",\n \"The HMD 62 comprises an optical see-through component and a display component.\",\n \"Optionally, the HMD 62 is configured to operate according to a first mode of operation when the occupant looks at the direction of the vehicle window and the light shading module 61 is in the first state, and to operate according to a second mode of operation when the occupant looks at the direction of the vehicle window and the light shading module 61 is in the second state.\",\n \"The total intensity of the VST light, emitted by the display component and reaching the occupant's eyes, is higher in the second mode than in the first mode.\",\n \"In one embodiment, in the first mode, intensity of light that reaches the occupant's eyes via the optical see-through component is higher than intensity of light from the VST that is emitted by the display component and reaches the occupant's eyes.\",\n \"And in the second mode, the intensity of light from the environment that reaches the occupant's eyes via the optical see-through component is lower than the intensity of light from the VST that is emitted by the display component and reaches the occupant's eyes.\",\n \"In one example, the total intensity of VST light, emitted by the display component and reaching the occupant's eyes, is at least 50% higher in the second mode than in the first mode.\",\n \"In some embodiments, the display component may be based on a digital display that produces the virtual image (such as in Oculus rift), direct retina illumination (such as in Magic Leap), or other methods that are capable of producing the virtual image.\",\n \"In one embodiment, the system described above optionally includes an occupant tracking module configured to calculate the point of view of the occupant based on measurements of a sensor.\",\n \"Optionally, the occupant tracking module is the HMD tracking module 27.Optionally, in this embodiment, the processor is further configured to render the VST based on data received from the occupant tracking module.\",\n \"Optionally, the display is a three dimensional (3D) display configured to show the occupant the VST, such that point of gaze of the occupant, while looking via the 3D display device, is most of the time beyond the location of the light shading module 61.In some embodiments, an occupant of a vehicle may have the opportunity to view video see-through (VST), which is video generated based on video of the environment outside the vehicle.\",\n \"VST can often replace the need to look out of a window (if the vehicle has windows).\",\n \"Some examples of scenarios in which VST may be available in a vehicle include a windowless vehicle, a vehicle with shaded windows having VLT below 30%, and/or when the occupant wears a VR headset.\",\n \"While traveling in such a vehicle, the occupant may benefit from gaining a view to the outside environment when an unexpected driving event occurs.\",\n \"By being made aware of the event, the occupant is less likely to be surprised, disturbed, and/or distressed by the event.\",\n \"While traveling in a vehicle, an occupant of the vehicle may not always be aware of the environment outside and/or of what actions the vehicle is about to take (e.g., breaking, turning, or hitting a speedbump).\",\n \"Thus, if such an event occurs without the occupant being aware that it is about to happen, this may cause the occupant to be surprised, disturbed, distressed, and even physically thrown off balance (in a case where the event involves a significant change in the balance of the physical forces on the occupant).\",\n \"This type of event is typically referred to herein as a Sudden Decrease in Ride Smoothness (SDRS) event.\",\n \"Some examples of SDRS events include at least one of the following events: hitting a speed bump, driving over a pothole, climbing on the curb, making a sharp turn, a hard breaking, an unusual acceleration (e.g., 0-100 km/h in less than 6 seconds), and starting to drive after a full stop.\",\n \"In some embodiments, an SDRS event takes place at least 2 minutes after starting to travel and it is not directly related to the act of the starting to travel.\",\n \"Additionally, the SDRS event takes place at least 2 minutes before arriving to the destination and is not directly related to the act of arriving at the destination.\",\n \"In one example, a sentence such as “an SDRS event is imminent” refers to an SDRS event that is: (i) related to traveling in the vehicle, and (ii) expected to happen in less than 30 seconds, less than 20 seconds, less than 10 seconds, or less than 5 seconds.\",\n \"In another example, a sentence such as “an SDRS event is imminent” may refer to an event that starts at that instant, or is about to start within less than one second.\",\n \"The following is a description of an embodiment of a video system that may be used to increase awareness of an occupant of a vehicle regarding an imminent SDRS.\",\n \"In one embodiment, a video system for an autonomous on-road vehicle includes at least autonomous-driving control system 65, a camera (such as camera 12), a processor (such as processor 18), and video module 66.FIG.\",\n \"17 is a schematic illustration of at least some of the relationships between the system elements mentioned above.\",\n \"The autonomous-driving control system 65 is configured to generate, based on trajectory of the vehicle and information about the road, an indication indicative of whether a Sudden Decrease in Ride Smoothness (SDRS) event is imminent.\",\n \"Optionally, the autonomous-driving control system 65 receives at least some of the information about the road from at least one of the following sources: sensors mounted to the vehicle, sensors mounted to nearby vehicles, an autonomous-driving control system 65 used to drive a nearby vehicle, and a database comprising descriptions of obstacles in the road that are expected to cause intense movement of the vehicle.\",\n \"In one example, the database comprising the descriptions of the obstacles includes one or more of the following types of data: locations of speed bumps, locations of potholes, locations of stop signs, and locations of sharp turns in the road.\",\n \"In one embodiment, the autonomous-driving control system 65 is configured to generate the indication indicative of whether an SDRS event is imminent based on at least one of the following configurations: (i) the autonomous-driving control system 65 receives images of the road from a camera, and calculates the indication based on the vehicle trajectory and image analysis of the images, (ii) the autonomous-driving control system 65 receives from a radar reflections of electromagnetic waves from the road, and calculates the indication based on the vehicle trajectory and signal processing of the reflections, and (iii) the autonomous-driving control system 65 receives a notification from a detailed road map, and calculates the indication based on the vehicle trajectory and the notification.\",\n \"The camera, which is mounted to the vehicle, is configured to take video of the environment outside the vehicle.\",\n \"Optionally, the data captured by the camera comprises 3D data.\",\n \"The processor is configured to generate a video see-through (VST) based on the video taken by the camera.\",\n \"The video module 66 is configured to select a first mode of presentation, in which a video-unrelated-to-the-VST (VUR) is presented on the foveal vision region of the occupant, at eye level, responsive to the indication not indicating that an SDRS event is imminent.\",\n \"The video module 66 is further configured to select a second mode of presentation, in which the VST is presented on the foveal vision region of the occupant, at eye level, responsive to the indication indicating that an SDRS event is imminent.\",\n \"Optionally, the VST captures more than 50% of the foveal vision region of the occupant in the second mode of presentation.\",\n \"In some embodiments, presenting video on the foveal vision region comprises presenting images with at least 50% transparency.\",\n \"Herein, “foveal vision” refers to an angle of about 5° of the sharpest field of vision.\",\n \"In one embodiment, in the first mode of presentation, the VUR is presented on the foveal vision region of the occupant with opacity A, and the VST is presented on the foveal vision region of the occupant with opacity B, where A>B>0.Optionally, a normalized opacity parameter takes a value from 0.0 to 1.0, and the lower the value the more transparent the video is.\",\n \"In this embodiment, in the second mode of presentation, the VUR is presented on the foveal vision region of the occupant with opacity A′, and the VST is presented on the foveal vision region of the occupant with opacity B′, where B′>B and B′>A′.\",\n \"In optional embodiments, one or more of the following values may be true: A′>0, B=0, and A′=0.Herein, “partially transparent” refers to opacity below one and above zero.\",\n \"Having the VST presented when an SDRS event is imminent can make the occupant be aware and prepared for the SDRS event.\",\n \"Thus, the occupant is less likely to be startled, distressed, and/or physically thrown off balance by the SDRS event.\",\n \"In one example, the SDRS event involves hitting a speedbump, while the occupant views a movie.\",\n \"About 5 seconds prior to hitting the speedbump, a partially transparent window displaying VST in which the speedbump is highlighted (e.g., flashing red) is presented on the foveal vision region of the occupant for a couple seconds (e.g., by being presented in the center of the movie).\",\n \"This way upon hitting the speedbump, the occupant is not startled by the event.\",\n \"In another example, the autonomous-driving control system 65 determines that a “hard breaking” is required, e.g., in order to avoid collision with a vehicle ahead that slowed unexpectedly.\",\n \"In this example, the occupant may be working on a virtual desktop, and within 100 milliseconds of when the determination is made that the vehicle is about to rapidly deaccelerate (a “hard breaking”), the VST depicting the rear of the vehicle ahead is displayed in the center of the virtual desktop.\",\n \"This way the occupant is immediately made aware of why the vehicle is breaking and this notification may prompt the occupant to seek a more appropriate posture for the breaking.\",\n \"Some illustrations of utilization of the different modes of operation are given in the following figures.\",\n \"FIG.\",\n \"18a illustrates presenting VUR responsive to not receiving from the autonomous-driving control system 65 an indication that an SDRS event is imminent.\",\n \"This figure has two parts, the left part shows the vehicle driving over a clean road, and the right part shows the VUR.\",\n \"FIG.\",\n \"18b illustrates presenting VST responsive to receiving from the autonomous-driving control system 65 an indication that an SDRS event is imminent.\",\n \"The figure has two parts, the left part shows the vehicle about to drive over a pothole, and the right part shows a small window showing the pothole over the VUR (optionally to warn the occupant).\",\n \"FIG.\",\n \"18c illustrates presenting VST responsive to receiving from the autonomous-driving control system 65 an indication that an SDRS event is imminent.\",\n \"The figure has two parts, the left part shows the vehicle about to enter a sharp turn, and on the right part shows a small window showing the sharp turn over the VUR (optionally to warn the occupant).\",\n \"Traditional vehicles typically have a front windshield that offers occupants of the vehicle a frontal view of the outside environment.\",\n \"However, in some embodiments, this frontal view may be provided using the VST.\",\n \"For example, in one embodiment, the vehicle includes a nontransparent element, which is coupled to the vehicle, and obstructs at least 30 degrees out of the frontal horizontal unaided FOV to the outside environment of an occupant at eye level.\",\n \"In one example of a standard vehicle, such as Toyota Camry model 2015, the frontal horizontal unaided FOV extends from the left door through the windshield to the right door.\",\n \"The use of the nontransparent element improves the safety of the occupant during a collision compared to a similar vehicle having the same total weight and comprising a transparent glass window instead of the nontransparent element.\",\n \"The nontransparent element may be coupled to the vehicle in various configurations, in embodiments described herein.\",\n \"In one embodiment, the nontransparent element is fixed to the vehicle at an angle, relative to the occupant, that is covered by the field of view of the VST, and the nontransparent element features visible light transmittance (VLT) below 10% of ambient light.\",\n \"Various types of displays may be utilized to present the occupant with video (e.g., the VST and/or the VUR).\",\n \"In one embodiment, the video is presented to the occupant on a screen coupled to the vehicle compartment.\",\n \"In one example, the screen coupled to the vehicle compartment utilizes parallax barrier technology.\",\n \"A parallax barrier is a device located in front of an image source, such as a liquid crystal display, to allow it to show a stereoscopic image or multiscopic image without the need for the viewer to wear 3D glasses.\",\n \"The parallax barrier includes a layer of material with a series of precision slits, allowing each eye to see a different set of pixels, thus creating a sense of depth through parallax.\",\n \"In another embodiment, the occupant wears a head-mounted display (HMD), and the HMD is used to present the video to the occupant.\",\n \"Optionally, the HMD is a VR headset, and as a result of presenting the VST, the occupant does not need to remove the VR headset in order to see the cause of the SDRS event.\",\n \"In some embodiments, the video module 66 may be selective regarding indications of which SRDS events may prompt it to operate in the second mode of operation.\",\n \"For example, if the occupant is engaged in a game, the video module 66 may refrain from presenting the VST in the foveal vision region if the vehicle is about to make a sharp turn.\",\n \"However, it may optionally still present the VST in the foveal vision region if the SDRS event involves something that may be more forcefully felt by the occupant, such as extreme evasive maneuvering performed to avoid a collision.\",\n \"In some embodiments, the video module 66 may determine whether to show a VST responsive to an SRDS event (in the second mode of operation) based on the level of concentration of the occupant.\",\n \"For example, if the occupant is deeply engaged in a certain activity (e.g., in work or playing a game) above a threshold, the video module 66 may refrain from operating in the second mode for certain SDRS events that would cause the video module 66 to operate in the second mode were the occupant engaged in the certain activity below the threshold.\",\n \"In one example, the engagement level may be based on the occupant's level of concentration, as measured by a wearable sensor (such as an EEG headset or a smartwatch) or a sensor fixed to the compartment (such as an eye tracker, a thermal camera, or a movement sensor embedded in the seat).\",\n \"Presenting an occupant of a vehicle with video see-through (VST) of the outside environment from a point of view of the occupant can help the occupant be prepared for various events that may be considered to cause a Sudden Decrease in Ride Smoothness (SDRS events).\",\n \"Some examples of SDRS events include the following events: hitting a speed bump, driving over a pothole, climbing on the curb, making a sharp turn, a hard breaking, an unusual acceleration (e.g., 0-100 km/h in less than 6 seconds), and starting to drive after a full stop.\",\n \"In order for the occupant to become aware of an imminent SDRS event, the VST needs to be presented in an attention-grabbing way.\",\n \"For example, when an SDRS event is imminent, the VST that describes the environment is brought to the center of the occupant's attention by displaying it at eye level and/or increasing the size of the VST (compared to other times when an SDRS event is not imminent).\",\n \"The following is a description of an embodiment of a video system that may be used to increase awareness of an occupant of a vehicle regarding an imminent SDRS by making the VST more prominent for an imminent SDRS.\",\n \"In one embodiment, a video system for an autonomous on-road vehicle includes at least the autonomous-driving control system 65, a camera, and a processor.\",\n \"In this embodiment, the occupant is engaged, at least part of the time, in entertainment- or work-related activities, which involve presentation of video-unrelated-to-the-VST (VUR) to the occupant, for example, on a screen coupled to the compartment of the vehicle or a HMD worn by the occupant.\",\n \"Some examples of such content (common in the year 2016) include cinema movies, broadcast TV shows, standard web browsers, and Microsoft Office 2016 applications (such as Word, Excel and PowerPoint).\",\n \"The camera, which is mounted to the vehicle, is configured to take video of the environment outside the vehicle.\",\n \"The processor is configured to generate, based on the video taken by the camera, a video see-through (VST) of outside environment from a point of view of an occupant of the vehicle.\",\n \"Optionally, the occupant is in a front seat of the vehicle (such that no other occupant in the vehicle is positioned ahead of the occupant).\",\n \"In some embodiments, the processor is configured to present video, which may include VUR and/or VST, to the occupant using different presentation modes, depending on whether an SDRS event is imminent.\",\n \"For example, the video may be presented according to first or second modes, depending on whether an SDRS event is imminent.\",\n \"Optionally, the VST captures in the video according to the first mode a diagonal FOV of at least 3°, 5°, or 10° of the occupant's FOV.\",\n \"Optionally, the VST is not presented in the foveal vision region of the occupant in the video according to the first mode, while the VST is presented in the foveal vision region of the occupant in the video according to the second mode.\",\n \"In one embodiment, responsive to an indication that is not indicative of an imminent SDRS event (generated by the autonomous-driving control system 65), the processor is configured to provide the occupant video according to the first mode.\",\n \"In the video according to the first mode, the occupant is presented with video that comprises a video-unrelated-to-the-VST (VUR) at eye level in the direction of forward traveling.\",\n \"Additionally, the video may comprise a video see-through (VST) of outside environment that is not presented at eye level in the direction of forward traveling.\",\n \"Receiving an indication indicative that an SDRS event is imminent may change the way video is presented to the occupant.\",\n \"Optionally, this change is made without receiving a command to do so from the occupant.\",\n \"In one embodiment, responsive to the indication indicating that an SDRS event is imminent, the processor is configured to provide video to the occupant video according to the second mode.\",\n \"In the video according to the second mode, the occupant is presented with video that comprises the VST, presented at eye level in the direction of forward traveling.\",\n \"Optionally, if the video according to the first mode includes VST, then the size of the VST window in the video according to the second mode is larger by at least 25% relative to the size of the VST window in the video according to the first mode.\",\n \"Optionally, the video according to the second mode includes presenting the VUR in the background (e.g., the VST is overlaid above the VUR).\",\n \"Optionally, while providing the video according to the second mode, responsive to an updated indication that does not indicate that an SDRS event is imminent, the processor is further configured to switch back to provide the video according to the first mode to the occupant.\",\n \"The following figures illustrate various ways in which the videos according to the first and second modes may be utilized.\",\n \"FIG.\",\n \"19a illustrates presenting a VUR, which is a movie showing a person skiing, responsive to not receiving from the autonomous-driving control system 65 an indication that an SDRS event is imminent.\",\n \"This figure has two parts, the left part shows the vehicle driving over a clean road, and the right part shows the VUR with a small VST on the right.\",\n \"FIG.\",\n \"19b illustrates presenting a VST responsive to receiving from the autonomous-driving control system 65 an indication that an SDRS event is imminent.\",\n \"This figure has two parts, the left part shows the vehicle about to drive over a speed bump, and the right part shows the VUR but now with a big VST on the right.\",\n \"In this example, the big VST captures about half of the VUR and shows the speed bump.\",\n \"FIG.\",\n \"19c illustrates presenting a partially transparent VST responsive to receiving from the autonomous-driving control system 65 an indication that an SDRS event is imminent.\",\n \"Here, the big VST (that captures about half of the VUR and shows the speed bump) is presented as partially transparent layer over the VUR in order to show the occupant both the VUR and the VST.\",\n \"In one embodiment, presenting to the occupant video according to the second mode involves presenting the VUR behind the VST, and the size and location of the VUR in the video according to the second mode is essentially the same as the size and location of the VUR in the video according to the first mode.\",\n \"Optionally, this means that there is a difference of less than 10% in the size and location of the VURs in the videos according to the first and second modes.\",\n \"In another embodiment, the VUR is presented in a diagonal FOV of at least 10 degrees, and is not based on the video taken by the camera.\",\n \"In some embodiments, the VUR may be unrelated to the purpose of the traveling in the vehicle.\",\n \"For example, the VUR may include videos related to the following activities: watching cinema movies, watching TV shows, checking personal emails, playing entertainment games, and surfing in social networks.\",\n \"In some embodiments, the occupant's field of view (FOV) to the outside environment is obstructed by a nontransparent element, and the VST represents at least a portion of the obstructed FOV.\",\n \"Optionally, the occupant uses a VR headset and the obstruction is due to a nontransparent element belonging to the VR headset.\",\n \"Additionally or alternatively, the obstruction may be due to the vehicle's compartment; in this case the nontransparent element may be an SAEDP, a safety beam, and/or a crumple zone at eye level, which obstruct at least 30 degrees out of the frontal horizontal unaided FOV to the outside environment of the occupant at eye level.\",\n \"When traveling in a vehicle, an occupant of the vehicle may not always be viewing the outside environment.\",\n \"For example, the occupant may be engaged in work- or entertainment-related activities.\",\n \"Additionally, in some vehicles, the occupant may not have a good view of the outside environment most of the time, or even all of the time.\",\n \"For example, the vehicle may have very few (or no) windows, or the vehicle may have a shading mechanism that reduces the light from the outside.\",\n \"However, there are times when the occupant should be made aware of the outside environment, even though the occupant may not be actively driving the vehicle.\",\n \"For example, the occupant may be made aware of the outside environment in order to make the occupant prepared for an event that causes a Sudden Decrease in Ride Smoothness (an SDRS event).\",\n \"Some examples of SDRS events include the following events: hitting a speed bump, driving over a pothole, climbing on the curb, making a sharp turn, a hard breaking, an unusual acceleration (e.g., 0-100 km/h in less than 6 seconds), and starting to drive after a full stop.\",\n \"In order for the occupant to become aware of an imminent SDRS event, in some embodiments that involve a vehicle that has a shading module that controls how much ambient light is let in, when an SDRS event is imminent the vehicle may increase the amount of light that enters via a window.\",\n \"This additional light can give an occupant a better view of the outside environment, which can make the occupant aware and better prepared for the SDRS.\",\n \"The following is a description of an embodiment of a system that may be used to increase awareness of an occupant of a vehicle regarding an imminent SDRS by enabling more ambient light to enter a vehicle via a window.\",\n \"In one embodiment, a shading system for a window of an autonomous on-road vehicle includes at least the autonomous-driving control system 65, a shading module, and a processor.\",\n \"FIG.\",\n \"20a illustrates a smart glass shading module that operates according to an indication that an SDRS event is not imminent.\",\n \"This figure has two parts, the left part shows the vehicle driving over a clean road, and the right part shows that the smart glass window blocks most of the ambient light (illustrated in the figure by the tree outside that is invisible to the occupant).\",\n \"FIG.\",\n \"20b illustrates the smart glass shading module that operates according to an indication that an SDRS event is imminent.\",\n \"This figure has two parts, the left part shows the vehicle about to drive over a pothole, and the right part shows that the smart glass window does not block the ambient light (illustrated in the figure by the tree outside that is visible to the occupant).\",\n \"The shading module is configured to control the amount of ambient light that enters the vehicle via the window.\",\n \"Optionally, the window is a front-facing window (e.g., a windshield).\",\n \"Optionally, the window is a side-facing window.\",\n \"There are various types of shading modules that may be utilized in different embodiments.\",\n \"In one embodiment, the shading module comprises a curtain.\",\n \"Optionally, the curtain covers most of the area of the window.\",\n \"Optionally, the curtain may open and close with the aid of an electromechanical device, such as a motor, based on commands issued by the processor.\",\n \"In another embodiment, the shading module is a movable physical element configured to reduce the intensity of the ambient light entering through the vehicle window into the vehicle compartment.\",\n \"For example, the shading module may include various forms of blinds, a shutter, or a sliding element.\",\n \"Optionally, the shading module may be unfurled on the inside of the vehicle compartment in order to block more than 70% of the ambient light intensity.\",\n \"Optionally, the shading module may be unfurled on the outside of the vehicle compartment in order to block more than 70% of the ambient light intensity.\",\n \"In yet another embodiment, the shading module comprises a smart glass able to change its light transmission level.\",\n \"Optionally, the smart glass is a vehicle window smart glass that comprises suspended particle devices (SPDs) film.\",\n \"Smart glass window may also be known as a switchable glass, a smart window, and/or a switchable window.\",\n \"Smart glass is glass or glazing whose light transmission properties are altered when voltage, current, light or heat is applied.\",\n \"Examples of electrically switchable smart glass include: suspended particle devices (SPDs), electrochromic devices, transition-metal hydride electrochromics devices, modified porous nano-crystalline films, polymer dispersed liquid crystal devices, micro-blinds, and thin coating of nanocrystals embedded in glass.\",\n \"Examples of non-electrical smart glass include: mechanical smart windows, Vistamatic®, and Sunvalve.\",\n \"The processor is configured to command the shading module to operate in different modes based on indications generated by the autonomous-driving control system 65.In some embodiments, the processor is configured to command the shading module to operate in different modes that allow different amounts of the ambient light to enter the vehicle via the window, depending on whether an SDRS event is imminent.\",\n \"For example, shading module may operate in first or second modes, depending on whether an SDRS event is imminent.\",\n \"Optionally, in the first mode the shading module blocks more of the ambient light entering through the vehicle window than in the second mode.\",\n \"Optionally, the increased ambient light in the second mode can help make the occupant more aware of the outside environment, which can enable the occupant to prepare for the SDRS event.\",\n \"In one embodiment, responsive to an indication that no SDRS event is imminent, the processor is configured to command a shading module to operate in a first mode in which the shading module blocks more than 30% of ambient light entering through a window of the vehicle.\",\n \"Receiving an indication indicative that an SDRS event is imminent may change the amount of ambient light that enters the vehicle via the window.\",\n \"Optionally, this change is made without receiving a command to do so from the occupant.\",\n \"In one embodiment, responsive to an indication that an SDRS event is imminent, the processor is configured to command the shading module to operate in the second mode in which the shading module blocks less than 90% of the ambient light entering through the vehicle window.\",\n \"Some aspects of this disclosure include a system that can show an occupant of a vehicle and Object Of Interest (OOI) in the outside environment, which the occupant would otherwise miss (e.g., due to being engaged in work- or entertainment-related activities and/or having no direct view of the outside environment).\",\n \"In one embodiment, a system configured to identify an Object Of Interest (OOI) in the outside environment, and to present to an occupant of an autonomous on-road vehicle a video see-through (VST) that comprises the OOI, includes at least a camera (such as camera 12), a processor (such as processor 18), and a video module (such as video module 66).\",\n \"Different types of things may be considered an OOI in different embodiments.\",\n \"In one embodiment, the OOI is selected from a set comprising: types of vehicles, types of scenery, and types of people.\",\n \"Optionally, the system may include a user interface configured to present a menu that enables the occupant to select the types of OOI, which when identified, will be presented in the second mode of presentation.\",\n \"In one example, an OOI may be any type of high-end vehicle (e.g., a Porsche).\",\n \"In another example, an OOI may include an ocean view.\",\n \"The camera, which is mounted to the vehicle, is configured to take video of the environment outside the vehicle.\",\n \"Optionally, the data captured by the camera comprises 3D data.\",\n \"The processor is configured to generate, based on the video taken by the camera, a video see-through (VST) of outside environment from a point of view of an occupant of the vehicle.\",\n \"Optionally, the occupant is in a front seat of the vehicle (such that no other occupant in the vehicle is positioned ahead of the occupant).\",\n \"The video module is configured to present, to the occupant, video that captures diagonal field of view (FOV) of at least 10 degrees, at eye level.\",\n \"Optionally, the video module is further configured to select a mode of operation based on whether an indication is received that is indicative of whether video taken by the camera include the OOI.\",\n \"Optionally, changing a mode of operation is done without an expressed command at that time by the occupant.\",\n \"In one embodiment, when not receiving an indication that the images includes the OOI, the video module is configured to select a first mode of presentation, in which a video-unrelated-to-the-VST (VUR) is presented on the foveal vision region of the occupant.\",\n \"And responsive to receiving the indication that the images include the OOI, the video module is further configured to select a second mode of presentation, in which the VST is presented on the foveal vision region of the occupant.\",\n \"There are various ways in which an indication of the OOI may be generated in different embodiments.\",\n \"In one embodiment, the system includes an image processing module configured to identify the OOI in the VST and to generate the indication.\",\n \"Various image processing techniques and/or image identification methods known in the art may be utilized by the image processing module for this task.\",\n \"In another embodiment, the system may include the autonomous-driving control system 65 configured to utilize a positioning system, such as GPS coordinates, to identify that the vehicle reached the OOI and to generate the indication.\",\n \"Optionally, the occupant may define which places may be OOIs and/or what types of locations are to be considered OOIs (e.g., historical monuments, nice scenery, etc.).\",\n \"In still another embodiment, the system may include a crowd-based module configured to identify the OOI based on feedback received from many different occupants who watched VSTs comprising the OOI.\",\n \"Optionally, this feedback may be derived based on indications of how other occupants felt about the VST (when it depicted certain content corresponding to OOIs).\",\n \"For example, points of interest may be determined according to affective crowd data, determine based on how other occupants felt about what they saw, and optionally find places where the crowd affective response was positive (e.g., blooming of flowers, etc.).\",\n \"Optionally, some occupants who watched the video related to the unhindered FOV for long periods (or have a physical window) may be monitored to see when an interesting view is encountered.\",\n \"Points of interest may involve items identified in the exterior environment using image analysis, including presenting the VST when one or more of the following happens: passing a fancy vehicle, passing someone the occupant knows, passing a vehicle accident, passing a police officer, having a sunset view, and passing an animal the occupant is interested in.\",\n \"In one embodiment, the system may receive an indication that the occupant is feeling at least one of nauseous and claustrophobic, and consequently present the VST in order to help the occupant to confront the feeling.\",\n \"For example, when there is a serious spike (e.g., increase in heart-rate and sweating), then the system may present the VST automatically.\",\n \"The system may also present a “normal” interior to the occupant (e.g., natural lighting settings).\",\n \"Optionally, when digital content is consumed (e.g., a game or a movie), the system may check whether the affective spike (e.g., increased excitement) is due to the content or due to the experience of being in the vehicle with AR or VR.\",\n \"If it is the former case, then the system might not present the VST.\",\n \"Some aspects of this disclosure involve an autonomous on-road vehicle that includes a nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) that is coupled to the compartment of the vehicle and is located, during normal driving, at eye level in front of an occupant who sits in a front seat of the vehicle.\",\n \"Additionally, the vehicle includes a stiff element that is configured to support the SAEDP and to resist deformation during collision in order to reduce compartment intrusion.\",\n \"The stiff element is located, during normal driving, at eye level between the SAEDP and the outside environment.\",\n \"Thus, the combination of the SAEDP and the stiff element offers the occupant an increased level of protection, e.g., in the case of a collision, compared to a vehicle in which a traditional window is in place at eye level in the front of the vehicle.\",\n \"However, due to it being nontransparent, placing the SAEDP at eye level may obstruct the occupant's view to the outside.\",\n \"Thus, in order to offer the occupant such a view, in some embodiments, the vehicle also includes a camera configured to take video of the outside environment in front of the occupant, and a computer configured to generate, based on the video, a representation of the outside environment in front of the occupant at eye level.\",\n \"This representation may be provided to the occupant using various types of displays.\",\n \"One non-limiting advantage of the vehicle described above is that it increases the safety of the occupant in the case of a collision, without prohibiting the occupant from obtaining a view of the outside environment.\",\n \"In one embodiment, an autonomous on-road vehicle includes a compartment, which one or more occupants may occupy while traveling in the vehicle (e.g., by sitting in seats).\",\n \"Coupled to the front of the compartment is a Shock-Absorbing Energy Dissipation Padding (SAEDP) and a stiff element that supports the SAEDP.\",\n \"Optionally, the SAEDP is nontransparent.\",\n \"The stiff element is located, during normal driving, at eye level between the SAEDP and the outside environment.\",\n \"Additionally, the vehicle includes a camera (e.g., camera 142 or structure 147 that comprises multiple cameras), which is configured to take video of the outside environment in front of the occupant, and a computer (e.g., computer 143) that is configured to generate, based on the video, a representation of the outside environment in front of the occupant at eye level.\",\n \"Optionally, the camera, and/or each of the cameras in the structure 147, may be based on at least one of the following sensors: a CCD sensor, a CMOS sensor, a near infrared (NIR) sensor, an infrared sensor (IR), and a device based on active illumination such as a LiDAR.\",\n \"Optionally, when the camera comprises multiple cameras, the multiple cameras are directed to multiple directions around the vehicle, and the multiple cameras support generating multiple representations of the outside environment from different points of view.\",\n \"It is to be noted that in some embodiments, the SAEDP may be fixed at its location both in normal driving and in times that are not considered to correspond to normal driving, while in other embodiments, the SAEDP may change its location during at least some of the times that do not correspond to normal driving.\",\n \"The SAEDP is coupled to the compartment in such a way that it is located, during normal driving, at eye level in front of an occupant who sits in a front seat of the vehicle.\",\n \"Different types of SAEDPs may be utilized in different embodiments.\",\n \"In one embodiment, the SAEDP comprises a passive material that is less stiff than a standard automotive glass window.\",\n \"The passive material is configured to protect the occupant's head against hitting the inner side of the vehicle compartment during a collision.\",\n \"Optionally, the passive material has thickness greater than at least one of the following thicknesses: 1 cm, 2 cm, 5 cm, 10 cm, 15 cm, and 20 cm.\",\n \"Optionally, the thickness of the passive material may refer to the average thickness of the SAEDP across the portion of the SAEDP at eye level.\",\n \"Alternatively, the thickness may refer to the maximal thickness at some position of the SAEDP (which is at least one of the values mentioned above).\",\n \"In another embodiment, the SAEDP comprises a pneumatic pad that is configured to inflate in order to protect the occupant's head against hitting the inner side of the vehicle compartment during collision.\",\n \"In some examples, the pneumatic pads may be formed from an elastomeric material providing chambers containing air or another gas.\",\n \"Optionally, the chambers are retained in compressed deflated condition until being inflated by the admission of gas pressure controlled by the vehicle's autonomous-driving control system that is responsible to estimate the probability and severity of an imminent collision.\",\n \"Additionally or alternatively, the chambers may be provided with restricted passages limiting the flow out from the chambers to provide shock-absorbing energy dissipation to reduce the rebound effect.\",\n \"U.S. Pat.\",\n \"No.\",\n \"5,382,051 discloses examples for pneumatic pads that can be used with some of the embodiments.\",\n \"In yet another embodiment, the SAEDP comprises an automotive airbag, which is configured to protect the occupant's head against hitting the inner side of the vehicle compartment during collision.\",\n \"In one example, during normal driving, the airbag is in a stowed state.\",\n \"The airbag is coupled to an inflator configured to inflate the airbag with gas to an inflated state, upon receiving an indication indicative of a probability of an impact of the vehicle exceeding a threshold.\",\n \"In this example, the airbag is located, when in the stowed state, at eye level in front of the occupant.\",\n \"In some embodiments, the compartment may include a door, and the SAEDP is physically coupled to the door from the inside, such that the SAEDP moves with the door as the door opens and/or closes.\",\n \"In some embodiments, the vehicle may include a second SAEDP coupled to the outer front of the vehicle to minimize damage to a pedestrian during a pedestrian-vehicle collision.\",\n \"In one embodiment, the stiff element that supports the SAEDP is nontransparent.\",\n \"In another embodiment, the stiff element may be automotive laminated glass or automotive tempered glass.\",\n \"Optionally, the structure of the vehicle comprises a crumple zone located at eye level between the stiff element and the outside environment.\",\n \"The representation of the outside environment is intended to provide the occupant with some details describing the outside environment.\",\n \"In some embodiments, the representation of the outside environment is generated from the point of view of the occupant, and it represents how a view of the outside environment would look like to the occupant, had there been a transparent window at eye level instead of the SAEDP and/or the stiff element.\",\n \"Optionally, a display is utilized to present the representation to the occupant.\",\n \"Various types of displays may be utilized in different embodiments to present the representation of the outside environment to the occupant.\",\n \"In one embodiment, the display is comprised in an HMD, and the vehicle further comprises a communication system configured to transmit the representation to the HMD.\",\n \"For example, the HMD may be a virtual reality system, an augmented reality system, or a mixed-reality system.\",\n \"In one embodiment, the display is supported by at least one of the SAEDP and the stiff element.\",\n \"For example, the display is physically coupled to the SAEDP and/or the stiff element.\",\n \"Optionally, the display is a flexible display.\",\n \"For example, the flexible display may be based on at least one of the following technologies and their variants: OLED, organic thin film transistors (OTFT), electronic paper (e-paper), rollable display, and flexible AMOLED.\",\n \"In one example, the display is flexible enough such that it does not degrade the performance of the SAEDP by more than 20% during a collision.\",\n \"In one example, the performance of the SAEDP is measured by hitting a crash test dummy head against the SAEDP and measuring the head's deceleration using sensors embedded in the head.\",\n \"FIG.\",\n \"21a, FIG.\",\n \"21b, and FIG.\",\n \"22 illustrate various embodiments of the vehicle described above.\",\n \"Each of the illustrated vehicles comprises a cross-section view of the vehicles, where each includes a compartment 145 for a single occupant (in FIG.\",\n \"21b) or more (in FIG.\",\n \"21a and FIG.\",\n \"22).\",\n \"In the figures, much of the compartment is covered with the SAEDP 140, which is nontransparent and comprises a soft passive material (cushiony in its nature).\",\n \"Supporting the SAEDP 140 is a stiff element 141, which in the illustrations comprises portions of the exterior (hull) of the vehicle which may optionally be made of one or more of the following materials: fiber-reinforced polymer, carbon fiber reinforced polymer, steel, and aluminum.\",\n \"The vehicles also include a camera (such as camera 142 and/or structure 147 that houses multiple cameras), which is positioned to capture a front view of the outside environment of the vehicle.\",\n \"Additionally, the vehicles include a computer 143, which may be positioned in various locations in the vehicle.\",\n \"In some embodiments, the computer may be comprised of multiple processors and/or graphics processors that may be located at various locations in the vehicle.\",\n \"The figures illustrate various types of displays that may be utilized to present the occupant with the representation of the outside environment generated by the computer 143 based on the video taken by the camera 142.In FIG.\",\n \"21a the representation is presented via an HMD 144, which may be, for example, a virtual reality HMD.\",\n \"In FIG.\",\n \"21b the representation is presented via an HMD 146, which may be, for example, a mixed-reality headset.\",\n \"And in FIG.\",\n \"22 the representation may be provided via one or more of the displays 150, which are coupled to the compartment.\",\n \"It is to be noted that in the figures described above not all of the described elements appear in each figure.\",\n \"The figures also illustrate various structural alternatives that may be implemented in different embodiments described herein.\",\n \"For example, FIG.\",\n \"21a illustrates a vehicle that includes window 148, which may optionally be an automotive tempered glass window, located in a location in which the head of a belted occupant is not expected to hit during collision.\",\n \"FIG.\",\n \"21b illustrates a vehicle that includes crumple zone 149, which is located at the front of the vehicle at eye level.\",\n \"The figure also illustrates the structure 147 that houses multiple cameras directed to multiple directions around the vehicle.\",\n \"In some embodiments, the representation of the outside environment may be manipulated in order to improve how the outside environment looks to the occupant.\",\n \"Optionally, this may be done utilizing the computer.\",\n \"In one example, manipulating the representation includes at least one of the following manipulations: converting captured video of an overcast day to video of a sunny day by preserving main items in the captured video (such as vehicles and buildings) and applying effects of a sunny day, converting unpleasant environment to a nice one, converting standard vehicles to futuristic or old fashion vehicles, and adding fans standing outside and waiving to the occupant.\",\n \"In one embodiment, the manipulation maintains the main items in the environment, such that the occupant would still know from the manipulated representation where he/she is traveling.\",\n \"In another embodiment, the manipulated representation maintains the main objects in the video of the outside environment, such that the main objects presented in the manipulated video essentially match the main objects that would have been seen without the manipulation.\",\n \"In some embodiments, the vehicle compartment may include an automotive laminated glass window or automotive tempered glass window located in a location where the head of a belted occupant is not expected to hit as a result of collision while traveling in velocity of less than 50 km/h, as illustrated by the dotted rectangle 148 in FIG.\",\n \"21a.\",\n \"In one embodiment, the structure of the vehicle is such that a crumple zone is located at eye level between the stiff element and the outside environment.\",\n \"Various types of vehicles may benefit from utilization of the nontransparent SAEDP supported by the stiff element and in conjunction with the camera and computer, as described above.\",\n \"The following are some examples of different characterizations of vehicles in different embodiments.\",\n \"In one embodiment, the vehicle weighs less than 1,500 kg without batteries, and it is designed to carry up to five occupants.\",\n \"In another embodiment, the vehicle weighs less than 1,000 kg without batteries, and it comprises an engine that is able to sustain continuously at most 80 horsepower.\",\n \"In yet another embodiment, the vehicle weighs less than 1,000 kg and it is designed to carry up to two occupants.\",\n \"In still another embodiment, the vehicle weighs less than 800 kg without batteries, and it comprises an engine that is able to sustain continuously at most 60 horsepower.\",\n \"In yet another embodiment, the vehicle weighs less than 500 kg without batteries and it comprises an engine that is able to sustain continuously at most 40 horsepower.\",\n \"And in still another embodiment, the vehicle weighs less than 400 kg without batteries and is designed to carry up to two occupants.\",\n \"Some aspects of this disclosure involve an autonomous on-road vehicle that includes a nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) that is coupled to the compartment and is located, during normal driving, at eye level to the left of the occupant who sits in a front seat of the vehicle (in the left front seat when the vehicle has more than one front seat).\",\n \"The SAEDP obstructs at least 30 degrees out of the horizontal unaided field of view (FOV) to the outside environment to the left of the occupant at eye level.\",\n \"Additionally, the vehicle includes a stiff element that is configured to support the SAEDP and to resist deformation during collision in order to reduce compartment intrusion.\",\n \"The stiff element is located, during normal driving, at eye level between the SAEDP and the outside environment.\",\n \"Thus, the combination of the SAEDP and the stiff element offers the occupant an increased level of protection, e.g., in the case of a collision to the left side of the vehicle, compared to a vehicle in which a traditional window is in place at eye level on the left side of the vehicle.\",\n \"However, due to it being nontransparent, placing the SAEDP at eye level may obstruct the occupant's view to the outside.\",\n \"Thus, in order to offer the occupant such a view, in some embodiments, the vehicle also includes a camera configured to take video of the outside environment to the left of the occupant, and a computer, which is configured to generate, based on the video, a representation of the outside environment to the left of the occupant at eye level.\",\n \"This representation may be provided to the occupant using various types of displays.\",\n \"One non-limiting advantage of the vehicle described above is that it increases the safety of the occupant in the case of a side collision, without prohibiting the occupant from obtaining a side view of the outside environment.\",\n \"In one embodiment, an autonomous on-road vehicle includes a compartment, which one or more occupants may occupy while traveling in the vehicle (e.g., by sitting in seats).\",\n \"Coupled to the compartment is a Shock-Absorbing Energy Dissipation Padding (SAEDP) and a stiff element that supports the SAEDP.\",\n \"Optionally, the SAEDP is nontransparent.\",\n \"The SAEDP is located, during normal driving, at eye level to the left of the occupant who sits in a front seat of the vehicle.\",\n \"The stiff element is located, during normal driving, at eye level between the SAEDP and the outside environment.\",\n \"Optionally, the stiff element is nontransparent.\",\n \"Optionally, the stiff element may be automotive laminated glass or automotive tempered glass.\",\n \"The vehicle also includes a camera (such as camera 161) that is configured to take video of the outside environment to the left of the occupant, and a computer that is configured to generate, based on the video, a representation of the outside environment to the left of the occupant at eye level.\",\n \"Optionally, the camera comprises multiple cameras directed to multiple directions around the vehicle, and the multiple cameras support generating multiple representations of the outside environment from different points of view.\",\n \"FIG.\",\n \"23 illustrates one embodiment of the autonomous on-road vehicle described above, which shows how an SAEDP protects the occupant during a collision.\",\n \"In the figure, SAEDP 160 (which may comprise a passive material) is coupled to the stiff element 141.When another vehicle collides with the side of the vehicle, the occupants head strikes the soft SAEDP 160, instead of a glass window (which would be positioned there in many conventional vehicles).\",\n \"The SAEDP is coupled to the compartment in such a way that it is located, during normal driving, at eye level to the left of the occupant who sits in a front seat of the vehicle.\",\n \"Optionally, due to its location, the SAEDP obstructs at least 30 degrees out of the horizontal unaided field of view (FOV) to the outside environment to the left of the occupant at eye level.\",\n \"Optionally, the SAEDP obstructs at least 45 degrees or at least 60 degrees out of the horizontal unaided FOV to the outside environment to the left of the occupant at eye level.\",\n \"In one example of a standard vehicle, such as Toyota Camry model 2015, the frontal horizontal unaided FOV extends from the left door through the windshield to the right door.\",\n \"In some embodiments, the SAEDP is fixed to the left door of the vehicle.\",\n \"In one embodiment, the vehicle has a single seat (occupied by the occupant).\",\n \"In another embodiment, the vehicle has two or more front seats and the occupant occupies the leftmost of the two or more front seats.\",\n \"Different types of SAEDPs may be utilized in different embodiments.\",\n \"In one embodiment, the SAEDP comprises a passive material, which is less stiff than a standard automotive glass window, having a thickness greater than at least one of the following thicknesses: 1 cm, 2 cm, 5 cm, 10 cm, 15 cm, and 20 cm.\",\n \"In other embodiments, the SAEDP may include an automotive airbag or a pneumatic pad that is configured to inflate in order to protect the occupant's head against hitting the inner side of the vehicle compartment during collision.\",\n \"In a similar fashion to how the SAEDP and stiff element are utilized to help protect the left side of the occupant, the same setup may be applied to the right side of the vehicle, in order to help protect that side.\",\n \"Thus, in some embodiments, the vehicle may further include a second SAEDP located at eye level to the right of the occupant who sits in the front seat, and a second stiff element located at eye level between the second SAEDP and the outside environment.\",\n \"Optionally, the second SAEDP obstructs at least 20 degrees out of the horizontal unaided FOV to the outside environment to the right of the occupant at eye level, and the computer is further configured to generate a second representation of the outside environment to the right of the occupant.\",\n \"Some aspects of this disclosure involve an autonomous on-road vehicle that includes a nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) that can cover a side window that enables an occupant of the vehicle to see the outside environment.\",\n \"The side window is located at eye level of an occupant who sits in the vehicle.\",\n \"A motor is configured to move the SAEDP over a sliding mechanism between first and second states multiple times without having to be repaired.\",\n \"A processor is configured to receive, from an autonomous-driving control system, an indication that a probability of an imminent collision reaches a threshold, and to command the motor to move the SAEDP from the first state to the second state.\",\n \"In the first state the SAEDP does not block the occupant's eye level view to the outside environment, and in the second state the SAEDP blocks the occupant's eye level view to the outside environment in order to protect the occupant's head against hitting the side window during collision.\",\n \"One non-limiting advantage of the vehicle described above is that it increases the safety of the occupant in the case of a side collision.\",\n \"In one embodiment, an autonomous on-road vehicle includes a side window 170, a nontransparent SAEDP (e.g., SAEDP 171), a motor 172, and a processor 175.The processor 175 is configured to receive, from an autonomous-driving control system (such as autonomous-driving control system 65), an indication indicating that a probability of an imminent collision reaches a threshold, and to command the motor 172 to move the SAEDP 171 from the first state to the second state.\",\n \"In the first state the SAEDP 171 does not block the occupant's eye level view to the outside environment, and in the second state, the SAEDP 171 blocks the occupant's eye level view to the outside environment in order to protect the occupant's head against hitting the side window during collision.\",\n \"Optionally, the processor is configured to command the motor 172 to start moving the SAEDP 171 to the second state at least 0.2 second, 0.5 second, 1 second, or 2 seconds before the expected time of the collision.\",\n \"The motor 172 is configured to move the SAEDP 171 over a sliding mechanism 173 between first and second states multiple times without having to be repaired.\",\n \"For example, during the same voyage, the SAEDP 171 may go up and down multiple times without a need for the occupant or anyone else to repair the SAEDP 171 and/or other components (such as motor 172 or the window 170) in order to the SAEDP 171 to be able to continue its operation correctly (i.e., continue moving up and down when needed).\",\n \"In some examples, the motor 172 is a motor designed to move the SAEDP 171 more than twice, more than 100 times, and/or more than 10,000 times without being replaced.\",\n \"The side window 170 is located at eye level of an occupant who sits in the vehicle, which enables the occupant to see the outside environment.\",\n \"In one embodiment, the side window 170 is a power window.\",\n \"In this embodiment, the power window comprises a window regulator that transfers power from a window motor 177 to the side window glass in order to move it up or down.\",\n \"The motor 172 is coupled to an SAEDP regulator that transfers power from the motor 172 to the SAEDP 171 in order to move it up or down.\",\n \"In this embodiment, the SAEDP regulator is located closer to the inner side of the compartment then the window regulator.\",\n \"Optionally, the motor 172 and the window motor 177 may be of the same type or of different types.\",\n \"In one embodiment, the SAEDP 171 comprises a passive material, which is less stiff than a standard automotive glass window, having thickness greater than at least one of the following thicknesses: 1 cm, 2 cm, 5 cm, 10 cm, 15 cm, and 20 cm.\",\n \"Optionally, the vehicle may include a storage space in a door of the vehicle, which is configured to store the SAEDP 171 in the first state.\",\n \"Additionally or alternatively, the vehicle may include a storage space in the roof of the vehicle, which is configured to store the SAEDP 171 in the first state.\",\n \"Optionally, the SAEDP 171 may move upwards when switching between the first and second states, and the top of the SAEDP has a profile (such as a triangle or a quarter sphere) which reduces the risk of catching the a part of the occupant (e.g., a finger or limb) or the occupant's clothing, between the top of the SAEDP 171 and an upper frame when moving the SAEDP 171 to the second state.\",\n \"In one embodiment, when switching the SAEDP 171 quickly between the first and second states, the SAEDP 171 is configured not to cover a range of 1 to 5 cm of the top height of the window.\",\n \"Optionally, keeping said range unoccupied reduces the risk of catching the occupant's fingers or limb by the edge of the SAEDP 171 when moving the SAEDP 171 to the second state.\",\n \"In some embodiments, the vehicle may include additional SAEDPs that cover additional regions of the vehicle's compartment (besides the side window 170).\",\n \"In one example, the vehicle includes an SAEDP 176 that covers at least a portion of the roof of the vehicle.\",\n \"In some embodiments, the vehicle includes a camera (e.g., camera 178a), which is configured to take video of the outside environment while the SAEDP 171 is in the second state.\",\n \"Additionally, in these embodiments, the vehicle may include a computer (such as computer 13), which is configured to generate a representation of the outside environment based on the video, and a display configured to present the representation of the outside environment to the occupant.\",\n \"The display may be physically coupled to the compartment and/or belong to an HMD.\",\n \"Optionally, the camera is fixed to the SAEDP 171, and thus moves along with the SAEDP 171 when it is moved between the first and second states.\",\n \"Optionally, the display is fixed to the SAEDP 171, and thus moves along with the SAEDP 171 when it is moved between the first and second states.\",\n \"Optionally, the display is configured to show, at eye level, a representation of the outside environment when the SAEDP is in the second state.\",\n \"In one example, the display is a flexible display.\",\n \"In another example, the camera comprises multiple cameras directed to multiple directions around the vehicle, and the computer is configured to generate at least two different representations of the outside environment, from at least two different points of view, for two occupants who sit in the vehicle.\",\n \"In some embodiments, in addition to raising the SAEDP 171, one or more of the displays mentioned above is utilized to present the occupant a video of the threat and the predicted trajectory that could result in the collision, in order to explain why the SAEDP 171 is being moved to the second state.\",\n \"FIG.\",\n \"24a and FIG.\",\n \"24b illustrate an example of a vehicle in which the side window may be covered by an SAEDP that can move up and down.\",\n \"The figures illustrate cross-sections of the vehicle, which show how the SAEDP 171 may move from the first state (in FIG.\",\n \"24a) to the second state (in FIG.\",\n \"24b).\",\n \"The dotted line 179 indicates that the SAEDP 171 does not close the entire gap over the window (e.g., in order to avoid catching the occupant's hair).\",\n \"The figures also illustrate sliding mechanism 173, which may be utilized to guide and assist in the movement of SAEDP 171.FIG.\",\n \"24b also illustrates camera 178a and display 178b, which are connected to a processor that generates, based on the video received from the camera, a view of the outside environment when an SAEDP (on the right side of the vehicle) is in the second state.\",\n \"The view of the outside environment is presented to the occupant on the display 178b.\",\n \"Camera and display on the left SAEDP 171, which correspond to camera 178a and display 178b, are not shown in the figure in order to make it clearer; however it is to be understood that such camera and display may be fitted to any relevant moving SAEDP.\",\n \"In one embodiment, the mechanism that moves the SAEDP 171 between the first and second states (referred to as the “SAEDP mechanism”) is similar to a power window regulator that moves an automobile window up and down.\",\n \"As with automobile power windows, the SAEDP regulator may be powered by an electric motor, which may come with the SAEDP regulator as one unit, or as a system that enables the motor or regulator to be replaced separately.\",\n \"The SAEDP mechanism includes a control system, a motor, a gear reduction, a sliding mechanism and the SAEDP, which are usually fixed on the door, but may alternatively be fixed on the roof as disclosed below.\",\n \"The sliding mechanism may have different architectures, such as Bowden type, double Bowden type, cable spiral, or crossed levers.\",\n \"In a first example, the SAEDP mechanism is similar to a double Bowden power window mechanism, in which the SAEDP 171 is fixed on two supports respectively constrained along two rails.\",\n \"The control system drives the motor that wraps two Bowden cables, which move two supports and, consequently, the SAEDP 171.A Bowden cable transmits mechanical force through the movement of an inner cable relative to an outer housing, and in the case of a DC motor, the basic operations of the motor are accomplished by reversing the polarity of its power and ground input.\",\n \"In a second example, the SAEDP mechanism is similar to a gear-drive type power window regulator; in this case, the SAEDP mechanism includes an SAEDP motor to power the mechanism, gear drive and geared arm to move the SAEDP 171 between the first and second states, and an SAEDP holding bracket to hold the SAEDP 171.In a third example, the SAEDP mechanism is similar to a cable type power window regulator; in this case, the SAEDP regulator includes an SAEDP motor that drives a wire cable though a mechanism, a series of pulleys that guide the cable, and a regulator carriage attached to the cable and to the SAEDP 171 and slides on the regulator track.\",\n \"One or more tracks may be mounted vertically inside the door panel that serves as a guide piece when the SAEDP 171 slides up and down.\",\n \"Depending on the design, the setup may have one main regulator track in the center of the door, or have a track on each side of the SAEDP.\",\n \"In a fourth example, the SAEDP regulator is similar to a scissor power window regulator; in this case, a motor operates a gear wheel that raises and lowers the SAEDP 171 by the use of a scissor action of rigid bars.\",\n \"The motor that moves the SAEDP 171 over the sliding mechanism may be any suitable motor, such as a DC electric motor, an AC electric motor, or a pneumatic motor.\",\n \"In one embodiment, the indication that the probability of an imminent collision reaches a threshold is received from the autonomous-driving control system 65 that calculates the probability based on the trajectory of the vehicle and information about the road.\",\n \"Optionally, the information about the road may be received from one of more of the following sources: a sensor mounted to the vehicle, a sensor mounted on a nearby vehicle, a road map, a stationary traffic controller nearby the vehicle, and a central traffic controller that communicates with the vehicle via wireless channel.\",\n \"In one embodiment, the processor 175 is further configured to receive an updated indication that the probability of the imminent collision does not reach a second threshold, and to command the motor to move the SAEDP to the first state.\",\n \"In this embodiment, the second threshold denotes a probability for a collision that is equal or lower than the threshold.\",\n \"FIG.\",\n \"25a and FIG.\",\n \"25b illustrate a motor configured to move a front nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) between first and second states.\",\n \"Some aspects of this disclosure involve an autonomous on-road vehicle that includes an outer nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) mounted to the front side of the vehicle during normal driving, such that the SAEDP is in front of and at eye level of an occupant who sits in a front seat of the vehicle.\",\n \"Additionally, the vehicle includes a camera that is mounted to the vehicle and is configured to take video of the outside environment in front of the occupant, and a computer configured to generate, based on the video, a representation of the outside environment at eye level for the occupant.\",\n \"One non-limiting advantage of the vehicle described above is that it increases the safety of a pedestrian in case of a vehicle-pedestrian collision, without prohibiting the occupant of the vehicle from receiving a frontal view of the outside environment.\",\n \"FIG.\",\n \"26a illustrates one embodiment of an autonomous on-road vehicle that includes outer nontransparent SAEDP 190, which is mounted to the front side of the vehicle during normal driving, such that the SAEDP 190 is in front of and at eye level of an occupant who sits in a front seat of the vehicle.\",\n \"The SAEDP 190 is less stiff than a standard automotive glass window and is designed to absorb some of the crashing energy transmitted to a pedestrian during a pedestrian-vehicle collision.\",\n \"Additionally, the vehicle includes a camera (such as camera 142), which is mounted to the vehicle and is configured to take video of the outside environment in front of the occupant, and a computer (such as computer 143), which is configured to generate, based on the video, a representation of the outside environment at eye level for the occupant.\",\n \"Optionally, the representation is generated from the point of view of the occupant.\",\n \"Optionally, the vehicle includes a display configured to present the representation to the occupant.\",\n \"For example, the display may belong to an HMD worn by the occupant.\",\n \"In another example, the display may be coupled to the compartment of the vehicle, and may be a flexible display.\",\n \"The SAEDP 190 may be implemented utilizing various approaches in different embodiments described herein.\",\n \"In one embodiment, the SAEDP 190 comprises a passive material.\",\n \"Optionally, the SAEDP 190 has thickness greater than at least one of the following thicknesses: 1 cm, 2 cm, 5 cm, 10 cm, 15 cm, and 20 cm.\",\n \"In another embodiment, the SAEDP 190 comprises an automotive airbag configured to inflate in order to protect the pedestrian.\",\n \"FIG.\",\n \"26b illustrates an outer SAEDP 190 that includes two air bags 192 configured to absorb some of the crashing energy transmitted to a pedestrian during a pedestrian-vehicle collision.\",\n \"Optionally, the airbag has a stowed condition and an inflated condition.\",\n \"The airbag is coupled to an inflator configured to inflate the airbag with gas, and the airbag is located, in the stowed condition, at eye level in front of the occupant.\",\n \"In this embodiment, the vehicle further includes an autonomous-driving control system, such as autonomous-driving control system 65, which is configured to calculate a probability of pedestrian-vehicle collision, based on measurements of sensors mounted to the vehicle, and to command the airbag to inflate before the pedestrian head hits the vehicle.\",\n \"In yet another embodiment, the SAEDP 190 comprises a pneumatic pad configured to inflate in order to protect the pedestrian.\",\n \"In this embodiment, the vehicle further includes an autonomous-driving control system, such as autonomous-driving control system 65, which is configured to calculate a probability of pedestrian-vehicle collision, based on measurements of sensors mounted to the vehicle, and to command the pneumatic pad to start inflate at least 0.5 second before the expected time of the collision in order to protect the pedestrian.\",\n \"Optionally, the pneumatic pad is reusable, and can be used multiple times without the need to be repaired.\",\n \"For example, the vehicle comprises a mechanism to deflate and/or stow the pneumatic pad, without requiring its repair and/or replacement.\",\n \"Some aspects of this disclosure involve an autonomous on-road vehicle that includes a window located at eye level of an occupant who sits in a front seat of the vehicle (e.g., a windshield), a reusable nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP), a motor, and a processor.\",\n \"The window enables the occupant to see the outside environment.\",\n \"The motor is configured to move the SAEDP over a sliding mechanism between first and second states multiple times without having to be repaired.\",\n \"In the first state the SAEDP does not block the occupant's eye level frontal view to the outside environment, and in the second state the SAEDP blocks the occupant's eye level frontal view to the outside environment.\",\n \"Additionally, in the second state the SAEDP can absorb some of the crashing energy transmitted to a pedestrian during a pedestrian-vehicle collision.\",\n \"The processor is configured to receive, from an autonomous-driving control system, an indication indicative of whether a probability of an imminent pedestrian-vehicle collision reaches a threshold.\",\n \"Responsive to receiving an indication of an imminent collision (e.g., within less than 2 seconds), the processor is configured to command the motor to move the SAEDP from the first state to the second state.\",\n \"One non-limiting advantage of the vehicle described above is that it increases the safety of a pedestrian in case of a vehicle-pedestrian collision, without prohibiting the occupant of the vehicle from receiving a frontal view of the outside environment during normal driving.\",\n \"FIG.\",\n \"27a and FIG.\",\n \"27b illustrate a motorized external SAEDP 121 that can move between first and second states multiple times.\",\n \"The figures illustrate how the SAEDP 121 can move from the first state (in FIG.\",\n \"27a) to the second state (FIG.\",\n \"27b) by having the motor 122 move the SAEDP 121 over sliding mechanism 123.Additionally, the figures illustrate optional camera 126 that is embedded in the SAEDP 121, and which may provide video to a processor configured to generate a representation of the outside environment when the SAEDP 121 is in the second state.\",\n \"In one embodiment, an autonomous on-road vehicle includes window 120, reusable SAEDP 121, motor 122, and processor 124.The window 120, which is located at eye level of an occupant who sits in a front seat of the vehicle, and which may be a windshield, enables the occupant to see the outside environment.\",\n \"The SAEDP 121 is reusable, i.e., it may be moved multiple times without the need to replace it or repair it after each use.\",\n \"The SAEDP 121 may be implemented utilizing various approaches in different embodiments described herein.\",\n \"In one embodiment, the SAEDP 121 comprises a passive material.\",\n \"Optionally, the SAEDP 121 has thickness greater than at least one of the following thicknesses: 1 cm, 2 cm, 5 cm, 10 cm, 15 cm, and 20 cm.\",\n \"In another embodiment, the SAEDP 121 comprises a pneumatic pad configured to inflate in order to protect the pedestrian.\",\n \"Optionally, the pneumatic pad is reusable, and the processor 124 is configured to command the pneumatic pad to start inflate at least 0.5 second before the expected time of the pedestrian-vehicle collision.\",\n \"The motor 122 is configured to move the SAEDP 121 over a sliding mechanism 123 between first and second states multiple times without having to be repaired.\",\n \"In the first state the SAEDP 121 does not block the occupant's eye level frontal view to the outside environment, and in the second state the SAEDP 121 blocks the occupant's eye level frontal view to the outside environment.\",\n \"When in the second state, the SAEDP 121 is configured to absorb some of the crashing energy transmitted to a pedestrian during a pedestrian-vehicle collision.\",\n \"The processor 124 is configured to receive, from an autonomous-driving control system (such as autonomous-driving control system 65), an indication indicative of whether a probability of an imminent pedestrian-vehicle collision reaches a threshold.\",\n \"Optionally, most of the time the vehicle travels, the processor 124 does not provide an indication that the probability reaches the threshold.\",\n \"Responsive to receiving an indication of an imminent collision (e.g., within less than 2 seconds), the processor 124 is configured to command the motor 122 to move the SAEDP 121 from the first state to the second state.\",\n \"Optionally, the processor 124 is configured to command the motor to start moving the SAEDP 121 to the second state at least 0.2 second, 0.5 second, 1 second, or 2 seconds before the pedestrian-vehicle collision in order to protect the pedestrian.\",\n \"In one example, the vehicle includes a sensor configured to detect the distance and angle between the vehicle and a pedestrian, and the autonomous-driving control system calculates the probability of the imminent pedestrian-vehicle collision based on the data obtained from the sensor, the velocity of vehicle and the possible maneuver.\",\n \"In one embodiment, the processor 124 is further configured to receive an updated indication that indicates the probability of the imminent pedestrian-vehicle collision does not reach a second threshold, and to command the motor 122 to move the SAEDP to the first state.\",\n \"Optionally, the second threshold denotes a probability for a pedestrian-vehicle collision that is equal or lower than the threshold.\",\n \"In one embodiment, the vehicle includes a camera (such as camera 126), which is configured to take video of the outside environment while the SAEDP 121 is in the second state.\",\n \"Additionally, in this embodiment, the vehicle may further include a computer configured to generate, based on the video, a representation of the outside environment, and a display configured to present the representation of the outside environment to the occupant while the SAEDP 121 is in the second state.\",\n \"Optionally, the camera 126 is fixed to the SAEDP 121 from the outer side, and thus moves with the SAEDP 121 when it moves between the first and second states.\",\n \"Optionally, the display is fixed to the SAEDP 121 from the inner side, and thus also moves with the SAEDP 121 when it moves between the first and second states; the occupant can see the display via the window 120 when the SAEDP is in the second state.\",\n \"In an alternative embodiment, the display is physically coupled to the compartment (such as a windshield that also functions as a display) and/or comprised in an HMD worn by the occupant.\",\n \"In addition to, or instead of, moving an SAEDP when a collision is imminent, in some embodiments, an imminent collision may prompt a raise of one or more power windows in the vehicle.\",\n \"This approach is illustrated in the following embodiment.\",\n \"In one embodiment, a safety system for an occupant of an autonomous on-road vehicle includes an automobile power window and an autonomous-driving control system (such as autonomous-driving control system 65).\",\n \"The autonomous-driving control system is configured to calculate probability of an imminent collision based on data received from sensors coupled to the vehicle.\",\n \"Responsive to detecting that the probability reaches a threshold, and at least one second before the expected collision, the autonomous-driving control system commands the power window to rise.\",\n \"In this embodiment, a raised power window provides an improved safety for the occupant of the vehicle during collision compared to a lowered power window.\",\n \"Optionally, responsive to detecting that the probability reaches the threshold, and at least two seconds before the expected collision, the autonomous-driving control system is configured to command the power window to rise.\",\n \"In one embodiment, the vehicle further includes an SAEDP coupled to the power window from the inside (e.g., as illustrated in FIG.\",\n \"24a and FIG.\",\n \"24b).\",\n \"In one embodiment, the power window is nontransparent, and the safety system for the occupant includes a display coupled to the power window from the inside.\",\n \"The display is configured to present to the occupant a video see-trough (VST) of the outside environment that is generated based on a video camera pointed at the outside environment.\",\n \"In another embodiment, the power window is made of a nontransparent material, which is stronger than a standard automotive tempered glass having the same dimensions.\",\n \"In this embodiment, the vehicle further comprises a camera configured to take video of the outside environment (such as camera 178a), and a computer configured to generate a VST to the outside environment based on the video.\",\n \"Optionally, the camera is physically coupled to the power window, such that the camera is raised and lowered with the power window.\",\n \"Additionally or alternatively, the camera may be coupled to an element of the vehicle that is not the power window, such that the camera does not move up and down when the power window is raised and lowered.\",\n \"Optionally, the vehicle further includes a display coupled to the inner side of the power window, such that the display is at eye level when the power window is raised, and below eye level when the power window is lowered; the display is configured to present the VST to the occupant.\",\n \"Optionally, the occupant wears an HMD, and the computer is configured to present the VST to the occupant on the HMD when the power window is raised, and not to present the VST to the occupant on the HMD when the power window is lowered.\",\n \"With autonomous vehicles, it is not necessary for occupants to sit.\",\n \"Some aspects of this disclosure involve autonomous vehicles in which an occupant of the vehicle may lay down.\",\n \"Such a design for an autonomous vehicle has the advantage of enabling a more comfortable position for certain activities (e.g., relaxing or sleeping).\",\n \"Additionally, such a vehicle may be built to be lower than traditional vehicles, which can offer advantages in terms of increased safety (e.g., a lower center of gravity offers better stability) and better vehicle aerodynamics.\",\n \"In order to increase the safety of the occupant, various forms of padding may be used in the compartment of the vehicle.\",\n \"In some embodiments, an autonomous on-road vehicle designed for lying down includes a closed compartment and a mattress, having an average thickness of at least 3 cm, which covers at least 50% of the compartment floor.\",\n \"In the compartment, there is a nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP), having an average thickness of at least 1 cm, which covers at least 50% of the compartment side walls and at least 60% of the compartment front wall during normal driving.\",\n \"Optionally, the SAEDP is supported by a stiff element that resists deformation during a collision in order to reduce compartment intrusion.\",\n \"Additionally, the vehicle includes a camera configured to take video of the outside environment, a computer configured to generate a representation of the outside environment based on the video, and a display configured to present the representation to the occupant.\",\n \"In one embodiment, an autonomous on-road vehicle designed for lying down includes a closed compartment 210, a mattress 211, an SAEDP 212 covering portions of the compartment 210, a camera (e.g., the structure 147 that houses multiple cameras), a computer (e.g., the computer 143), and a display 215.FIG.\",\n \"28 illustrates one embodiment of a vehicle compartment 210 in which an occupant may lay down.\",\n \"In the figure, the occupant is lying down on mattress 211, which covers the floor of the compartment 210, and is watching a movie on the display 215.The SAEDP 212 covers the front, roof, and back of the compartment 210.It is to be noted that the SAEDP 212 also covers portions of the side walls of the compartment 210, however, this is not illustrated to enable a clearer image of the embodiment.\",\n \"The figure also includes an airbag 216, which may be inflated below the SAEDP 212 in order to protect the occupant and restrain his/her movement in the case of a collision.\",\n \"The mattress 211 covers at least 50% of the compartment floor.\",\n \"Optionally, the mattress 211 covers at least 80% of the compartment floor.\",\n \"In one embodiment, the mattress 211 has an average thickness of at least 3 cm.\",\n \"In other embodiments, the average thickness of the mattress 211 is greater than at least one of the following thicknesses: 5 cm, 7 cm, 10 cm, 20 cm, and 30 cm.\",\n \"The SAEDP 212 is a nontransparent SAEDP, having an average thickness of at least 1 cm.\",\n \"Optionally, the SAEDP 212 covers at least 50% of the compartment side walls and at least 60% of the compartment front wall during normal driving.\",\n \"In one embodiment, the average thickness of the SAEDP 212 is greater than at least one of the following thicknesses: 2 cm, 3 cm, 5 cm, 10 cm, 15 cm, and 20 cm.\",\n \"In another embodiment, the SAEDP 212 covers at least 80% of the compartment side walls and at least 80% of the compartment front wall.\",\n \"In yet another embodiment, the SAEDP covers at least 50% of the compartment roof.\",\n \"In still another embodiment, the mattress and the SAEDP cover essentially the entire compartment interior.\",\n \"In addition to the SAEDP 212, in some embodiments additional measures may be employed in order to improve the safety of the occupant.\",\n \"In one embodiment, the vehicle includes an automotive airbag configured to deploy in front of the SAEDP 212 in order to protect the occupant, in addition to the SAEDP 212, against hitting the inner side of the vehicle compartment during a collision.\",\n \"It is noted that the meaning that the airbag deploys in front of the SAEDP is that the airbag deploys towards the inner side of the compartment.\",\n \"Optionally, the airbag has a stowed condition and an inflated condition, and the airbag is coupled to an inflator configured to inflate the airbag with gas upon computing a predetermined impact severity.\",\n \"The stowed airbags may be stored in various positions, such as stored essentially in the middle of the front wall, stored essentially in the middle of the rear wall, stored in the side walls (possibly two or more horizontally spaced airbags), and stored in the roof (possibly one or more airbags towards the front of the compartment and one or more airbags towards the rear of the compartment).\",\n \"In some embodiments, various additional safety measures may be utilized to improve the safety of the occupant while traveling, such as a sleeping net and/or a safety belt, as described for example in U.S. Pat.\",\n \"Nos.\",\n \"5,536,042 and 5,375,879.Stiff element 213 is configured to support the SAEDP 212 and to resist deformation during a collision in order to reduce compartment intrusion.\",\n \"Part of the stiff element 213 is located, during normal driving, at eye level between the SAEDP 212 and the outside environment.\",\n \"Optionally, the stiff element covers, from the outside, more than 80% of the SAEDP on the compartment side walls.\",\n \"Optionally, the vehicle also includes a crumple zone located at eye level between the stiff element 213 and the outside environment.\",\n \"In another embodiment, the vehicle includes a pneumatic pad configured to inflate in order to protect the occupant, in addition to the SAEDP 212, against hitting the inner side of the vehicle compartment during a collision.\",\n \"Optionally, the pneumatic pad is configured to deploy in front of the SAEDP 212 towards the inner side of the compartment.\",\n \"Alternatively, the pneumatic pad is located between the SAEDP 212 and the stiff element 213, and is configured to deploy behind the SAEDP 212.The pneumatic pad may be mounted to various locations, such as mounted to the front wall, mounted to the rear wall, mounted to the side walls, and/or mounted to the roof.\",\n \"The camera is configured to take video of the outside environment.\",\n \"The computer is configured to generate a representation of the outside environment based on the video.\",\n \"Optionally, the representation is generated from the point of view of the occupant.\",\n \"The display 215 is configured to present the representation to the occupant.\",\n \"In one embodiment, the display 215 is comprised in an HMD, and the vehicle further comprises a communication system configured to transmit the representation to the HMD.\",\n \"In another embodiment, the display 215 is physically coupled to at least one of the SAEDP 212 and the stiff element 213 at eye level of the occupant.\",\n \"Optionally, the display 215 is a flexible display.\",\n \"For example, the display 215 may be a flexible display that is based on at least one of the following technologies and their variants: OLED, organic thin film transistors (OTFT), electronic paper (e-paper), rollable display, and flexible AMOLED.\",\n \"Optionally, the display 215 is flexible enough such that it does not degrade the performance of the SAEDP by more than 20% during a collision.\",\n \"Having a vehicle compartment that is designed to allow an occupant to lay down comfortably can be done using various compartment designs, which may be different from the designs used in standard vehicles, in which occupants primarily sit up.\",\n \"In one example, the vehicle does not have an automotive seat with a backrest and safety belt, which enables the occupant to sit straight in the front two thirds of the compartment.\",\n \"In another example, the vehicle is designed for a single occupant, and the average distance between the mattress and the compartment roof is below 80 cm.\",\n \"In still another example, the vehicle is designed for a single occupant, and the average distance between the mattress and the compartment roof is below 70 cm.\",\n \"In still another example, the vehicle is designed for a single occupant, and the average distance of the compartment roof from the road is less than 1 meter.\",\n \"And in yet another example the vehicle is designed for a single occupant, and the average distance of the compartment roof from the road is less than 80 cm.\",\n \"It is to be noted that the use of the terms “floor”, “roof”, “side walls”, and “front wall” with respect to the compartment are to be viewed in their common meaning when one considers the compartment to be a mostly convex hull in 3D, such as having a shape that resembles a cuboid.\",\n \"Thus, for example, an occupant whose face faces forward, will see the front wall ahead, the floor when looking below, the roof when looking above, and a side wall when looking to one of the sides (left or right).\",\n \"In embodiments that do not resemble cuboids, alternative definitions for these terms may be used based on the relative region (in 3D space) that each of the portions of the compartment occupy.\",\n \"For example, the floor of the compartment may be considered to be any portion of the compartment which is below at least 80% of the volume of the compartment.\",\n \"Similarly, the roof may be any portion of the compartment that is above at least 80% of the volume of the compartment.\",\n \"The front wall may be any portion of the compartment that is ahead of at least 80% of the volume of the compartment, etc.\",\n \"Note that using this alternative definitions, some portions of the compartment may be characterized as belonging to two different regions (e.g., the front wall and the roof).\",\n \"Some aspects of this disclosure involve an autonomous on-road vehicle that includes a compartment having a large mirroring element located in front of an occupant who sits in a front seat of the compartment.\",\n \"Optionally, the mirroring element has height and width exceeding 25×25 cm, such that it covers a square that is at least those dimensions.\",\n \"Optionally, the mirroring element captures a region corresponding to at least 10×10 degrees, including a region spanning from the horizon to 10° below the horizon, of the occupant's forward field of view during normal driving.\",\n \"Additionally, the mirroring element provides an effect of reflecting more than 25% of the light arriving from the occupant's direction.\",\n \"In some embodiments, the vehicle has an advantage that it can increase the perceived compartment volume, which can make travelling in the vehicle more pleasurable for some people.\",\n \"FIG.\",\n \"29 illustrates one embodiment of a vehicle having a front mirroring element.\",\n \"The figure illustrates how the occupant 222 can see her reflection 223 in the mirroring element 220.In one embodiment, the mirroring element 220 is located in front of an occupant who sits in a front seat of the vehicle.\",\n \"The mirroring element 220 provides an effect of reflecting more than 25% of the light arriving from the occupant's direction.\",\n \"Optionally, the mirroring element 220 provides an effect of reflecting more than at least one of 50%, 80%, and 90% of the light arriving from the occupant's direction.\",\n \"Optionally, the mirroring element 220 increases the volume of the vehicle compartment as perceived by the occupant due to the reflection effect.\",\n \"In one embodiment, the mirroring element 220 has height and width exceeding 25×25 cm, such that it covers a square that is at least those dimensions.\",\n \"Optionally, the mirroring element 220 captures a region corresponding to at least 10×10 degrees, including a region spanning from the horizon to 10° below the horizon, of the occupant's forward field of view during normal driving.\",\n \"Optionally, the height and width of the mirroring element 220 is above 50×40 cm, and the mirroring element captures above 30×30 degrees of the occupant's field of view, including a region spanning from the horizon to 30° below the horizon.\",\n \"Optionally, the mirroring element 220 covers more than 25% of the area where a conventional windshield of a normal non-autonomous on-road vehicle in year 2016 is expected to be located.\",\n \"The mirroring element 220 may be implemented in different ways, in different embodiments.\",\n \"In one embodiment, the mirroring element 220 comprises an optical mirror that is essentially flat and perpendicular to the ground.\",\n \"In this embodiment, most of the effect of reflecting is generated by the optical mirror.\",\n \"In one example, an optical mirror that is essentially flat and perpendicular to the ground refers to an optical mirror having a radius of curvature greater than a meter and a deviation below ±30° from the perpendicular to the ground.\",\n \"In another embodiment, the mirroring element 220 comprises a Fresnel type optical reflector comprising many reflecting prisms.\",\n \"In this embodiment, the Fresnel type optical reflector is not flat, but the reflecting prisms are arranged in angles that reflect the light from the occupant such as to imitate a flat mirror.\",\n \"In one embodiment, the mirroring element 220 comprises an electronic display that operates based on a camera 221 configured to take video of the occupant 222, and a computer 224 configured to generate a digital representation of the occupant 223 based on the video of the occupant.\",\n \"In this case, most of the effect of reflecting is generated by light emitted by the electronic display (which is the output of the video of the occupant as generated by the computer 224).\",\n \"Due to the close proximity between the at least one camera 221 and the occupant, it may be necessary to stitch the reflecting effect of a large area from multiple cameras that capture the occupant from different angles.\",\n \"In one example, the camera 221 comprises first and second cameras, located to the right and left of the occupant, respectively.\",\n \"In another example, the camera 221 comprises first and second cameras, located above the level of the occupant's nose and below the level of the occupant's collarbone, respectively, and less than 80 cm away from the occupant.\",\n \"In still another embodiment, the effect of reflecting is achieved by a digital mirror that comprises multiple cameras embedded within the digital mirror and configured to take images of the occupant, and multiple light emitting pixels configured to emit light rays that generate the effect of reflecting.\",\n \"In one embodiment, the mirroring element 220 comprises an electronic display, and the vehicle further includes a camera configured to take video of the outside environment in front of the occupant, and a computer configured to generate, based on the video, a representation of the outside environment in front of the occupant at eye level, for displaying on the mirroring element 220.In addition to the effect of reflecting, in some embodiments the mirroring element 220 may also be configured to operate in a second state in which it provides an effect of reflecting less than 20% of the light arriving from the occupant's direction, and to present to the occupant the representation of the outside environment.\",\n \"Here, presenting the representation may imitate a transparent windshield to the outside environment.\",\n \"The vehicle may also include, in some embodiments, a display configured to present to the occupant, at eye level in front of the occupant, the representation of the outside environment instead of, or in addition to, the effect of reflecting.\",\n \"Optionally, the vehicle may include a user interface configured to enable the occupant to switch between seeing the effect of reflecting and seeing the representation of the outside environment.\",\n \"In one example, the display is comprised in a head-mounted display (HMD).\",\n \"In another example, the display is mechanically coupled to the compartment, and/or the mirroring element comprises the display.\",\n \"As described above, the effect of reflecting light that comes from the direction of the occupant may be obtained, in some embodiments, utilizing an HMD.\",\n \"The following is a more detailed example of such an embodiment.\",\n \"In one embodiment, an autonomous on-road vehicle includes a compartment comprising a front seat, a camera, a computer, a communication module, and an HMD.\",\n \"The camera is physically coupled to the vehicle, configured to take images of an occupant who sits in the front seat.\",\n \"The computer is configured to generate, based on the images, a video that shows a mirror effect.\",\n \"Herein, the “mirror effect” involves presenting the occupant with an image that is similar to an image that the occupant would see had there been an actual mirror in front of the occupant.\",\n \"Optionally, the system enables the occupant to have control on the synthetic mirror effect, such as control on the distance between the occupant and her image, and/or control on the width of the image.\",\n \"The communication module is configured to transmit the video to a head-mounted display (HMD) worn by the occupant, and the HMD is configured to present the video to the occupant, such that the occupant sees a representation of his or her reflection when looking forward at eye level.\",\n \"Optionally, the HMD is selected from the group comprising: a virtual reality headset, an augmented reality headset, and mixed reality headset.\",\n \"Optionally, the video presented to the occupant captures at least 30×30 degrees of the occupant's field of view, spanning at least from the horizon to 30° below the horizon.\",\n \"In one embodiment, the vehicle described above further includes a second camera configured to take a second set of images of the outside environment in front of the occupant.\",\n \"In this embodiment, the computer is further configured to generate a representation of the outside environment based on the second set of images, and the HMD is configured to present the representation of the outside environment instead of the video that shows the mirror effect or in addition to the video that shows the mirror effect.\",\n \"In one embodiment, the vehicle described above may include multiple cameras that capture images that are utilized by the computer to generate the video that shows the mirror effect.\",\n \"In one example, the vehicle comprises at least first and second cameras, which are located to the right and left of the occupant, respectively.\",\n \"In another example, the vehicle comprises at least first and second cameras, located above the level of the occupant's nose and below the level of the occupant's collarbone, respectively, and which are less than 80 cm away from the occupant.\",\n \"Some aspects of this disclosure involve utilizing one or more nontransparent side beams in order to help protect the occupant in a case of a collision.\",\n \"The one or more side beams are stiffer than automotive laminated glass.\",\n \"In one example, a side beam comprises a high tensile steel pipe and pressed material.\",\n \"In another example, a side beam comprises an aluminum extruded shape.\",\n \"In one embodiment, an autonomous on-road vehicle that weighs less than 1500 kg without batteries includes a nontransparent side beam, which is stiffer than automotive laminated glass, and is located during normal driving to the left and at eye level of an occupant who sits in a front seat.\",\n \"The vehicle also includes a camera configured to take video of the outside environment to the left of the occupant, and a computer configured to generate for the occupant, based on the video, a representation of the outside environment to the left of the occupant at eye level.\",\n \"Optionally, the representation is presented to the occupant using a display.\",\n \"In one example, the display is comprised in a head-mounted display (HMD), and the vehicle further comprises a communication system configured to transmit the representation to the HMD.\",\n \"In another example, the display is coupled to the inner side of the compartment.\",\n \"The following is a description of an embodiment of a vehicle in which one or more side beams may be utilized to help protect the left side of a vehicle (and an occupant therein).\",\n \"In one embodiment, an autonomous on-road vehicle includes a nontransparent side beam, a camera (e.g., the camera 161), and a computer (e.g., the computer 143).\",\n \"Optionally, the vehicle weighs less than 1500 kg without batteries.\",\n \"The nontransparent side beam, which is stiffer than automotive laminated glass, is located, during normal driving, at eye level to the left of an occupant who sits in a front seat of the vehicle.\",\n \"Optionally, the side beam is at least 60 cm long and at least 1 cm wide (herein “cm” refers to centimeters).\",\n \"In one example, the side beam comprises a high tensile steel pipe and pressed material.\",\n \"In another example, the side beam comprises an aluminum extruded shape.\",\n \"The camera configured to take video of the outside environment to the left of the occupant.\",\n \"The computer is configured to generate for the occupant, based on the video, a representation of the outside environment to the left of the occupant at eye level.\",\n \"Optionally, the representation is generated from the point of view of the occupant, and the vehicle further includes a display configured to present the representation to the occupant.\",\n \"In one example, the display is comprised in a head-mounted display (HMD), and the vehicle further comprises a communication system configured to transmit the representation to the HMD.\",\n \"In another example, the display is coupled to the inner side of the compartment.\",\n \"In some embodiments, a plurality of beams, which may be similar to the side beam described above, may be located in the region of the left side of the vehicle.\",\n \"It is to be noted that the plurality of beams may not necessarily all have the same dimensions or be made of the same exact materials.\",\n \"Optionally, the plurality of beams may be connected in various ways in order to form a structure that can better resist compartment deforming in the case of a collision.\",\n \"For example, in one embodiment, the vehicle includes an additional side beam that is not parallel to the side beam and crosses it to form an “X” shaped structure.\",\n \"Herein, an “X” shaped structure refers to any structure of two nonparallel beams that cross, and the two do not necessarily form a symmetric “X” (e.g., a symmetric “X” may be obtained when the two beams are of equal length and cross at their centers).\",\n \"This structure is illustrated in FIG.\",\n \"30a where beams 231 and 232 cross to form an “X” shape structure.\",\n \"It is to be noted that the beam 231 is at eye level (i.e., at least a portion of the beam 231 is at the same height as a typical occupant's eyes).\",\n \"FIG.\",\n \"30a illustrates one example of a configuration of a plurality of beams located in the left side of the vehicle.\",\n \"Different designs of vehicles may benefit from utilizing one or more sides beam as described above.\",\n \"In one embodiment, the side beam is embedded in a movable structure that changes its location with respect to the vehicle compartment.\",\n \"For example, the side beam may be part of a left door of the vehicle.\",\n \"In another embodiment, the side beam is embedded in the vehicle compartment itself and does not change its location with respect to the rest of the compartment.\",\n \"For example, the side beam may be placed in a compartment wall to the left of the occupant.\",\n \"In order to better protect the occupant from injury due to hitting the head against the side of the vehicle, in some embodiments, the vehicle may comprise a nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) located at eye level between the side beam and the occupant.\",\n \"The SAEDP is less stiff than a standard automotive glass window.\",\n \"In one example, the SAEDP comprises a passive material.\",\n \"In another example, the SAEDP includes an airbag.\",\n \"And in still another example, the SAEDP includes a pneumatic pad.\",\n \"Optionally, the vehicle includes a display on which the representation of the outside environment may be presented to the occupant.\",\n \"Optionally, the display is supported by the SAEDP and/or the side beam.\",\n \"Optionally, the display is a flexible display.\",\n \"In a similar fashion to the utilization of beams on the left side of the vehicle, in some embodiments, one or more beams may be used to help protect the occupant's right side.\",\n \"For example, in one embodiment, the vehicle includes a second side beam, located at eye level to the right of the occupant, and a second camera configured to take video of the outside environment to the right of the occupant.\",\n \"In this embodiment, the computer is further configured to generate a second representation of the outside environment to the right of the occupant.\",\n \"Some aspects of this disclosure involve utilizing one or more nontransparent beams in order to help protect the occupant in a case of a collision.\",\n \"The one or more beams are stiffer than automotive laminated glass.\",\n \"In one example, a nontransparent beam comprises a high tensile steel pipe and pressed material.\",\n \"In another example, a nontransparent beam comprises an aluminum extruded shape.\",\n \"In one embodiment, an autonomous on-road vehicle that weighs less than 1500 kg without batteries includes a nontransparent beam, which is stiffer than automotive laminated glass, and is fixed at eye level in front of an occupant who sits in a front seat of the vehicle during normal driving.\",\n \"The vehicle also includes a camera configured to take video of the outside environment in front of the occupant, and a computer configured to generate for the occupant, based on the video, a representation of the outside environment in front of the occupant at eye level.\",\n \"Optionally, the representation is presented to the occupant using a display.\",\n \"In one example, the display is comprised in a head-mounted display (HMD), and the vehicle further comprises a communication system configured to transmit the representation to the HMD.\",\n \"In another example, the display is coupled to the inner side of the compartment.\",\n \"The following is a description of an embodiment of a vehicle in which one or more nontransparent beams may be utilized to help protect the vehicle's front (and an occupant therein).\",\n \"In one embodiment, an autonomous on-road vehicle includes a nontransparent beam, a camera (e.g., the camera 142), and a computer (e.g., the computer 143).\",\n \"Optionally, the vehicle weighs less than 1500 kg without batteries.\",\n \"The nontransparent beam, which is stiffer than automotive laminated glass, is located, during normal driving, at eye level in front an occupant who sits in a front seat of the vehicle.\",\n \"Optionally, the nontransparent beam is at least 60 cm long and at least 1 cm wide (herein “cm” refers to centimeters).\",\n \"In one example, the nontransparent beam comprises a high tensile steel pipe and pressed material.\",\n \"In another example, the nontransparent beam comprises an aluminum extruded shape.\",\n \"The camera configured to take video of the outside environment in front of the occupant.\",\n \"The computer is configured to generate for the occupant, based on the video, a representation of the outside environment in front of the occupant at eye level.\",\n \"Optionally, the representation is generated from the point of view of the occupant, and the vehicle further includes a display configured to present the representation to the occupant.\",\n \"In one example, the display is comprised in a head-mounted display (HMD), and the vehicle further comprises a communication system configured to transmit the representation to the HMD.\",\n \"In another example, the display is coupled to the inner side of the compartment.\",\n \"In some embodiments, a plurality of beams, which may be similar to the nontransparent beam described above, may be located in the front of the vehicle.\",\n \"It is to be noted that the plurality of beams may not necessarily all have the same dimensions or be made of the same exact materials.\",\n \"Optionally, the plurality of beams may be connected in various ways in order to form a structure that can better resist compartment deformation in the case of a collision.\",\n \"For example, in one embodiment, the vehicle includes an additional nontransparent beam that is not parallel to the nontransparent beam and crosses it to form an “X” shaped structure.\",\n \"This structure is illustrated in FIG.\",\n \"30b where beams 235 and 236 cross to form an “X” shape structure.\",\n \"Both of the beams 235 and 236 are at eye level (i.e., at least a portion of each beam is at the same height as a typical occupant's eyes).\",\n \"FIG.\",\n \"30b illustrates one example of a configuration of a plurality of beams located in the front of the vehicle.\",\n \"Different designs of vehicles may benefit from utilizing one or more nontransparent beam as described above.\",\n \"In one embodiment, the nontransparent beam is embedded in a movable structure that changes its location with respect to the vehicle compartment.\",\n \"For example, the nontransparent beam may be part of a front door through which the occupant may enter the vehicle.\",\n \"In another embodiment, the nontransparent beam is embedded in the vehicle compartment itself and does not change its location with respect to the rest of the compartment.\",\n \"For example, the nontransparent beam may be placed in a compartment wall in front of the occupant.\",\n \"In order to better protect the occupant from injury (e.g., during a collision), in some embodiments, the vehicle may comprise a nontransparent Shock-Absorbing Energy Dissipation Padding (SAEDP) located at eye level between the nontransparent beam and the occupant.\",\n \"The SAEDP is less stiff than a standard automotive glass window.\",\n \"In one example, the SAEDP comprises a passive material.\",\n \"In another example, the SAEDP includes an airbag.\",\n \"And in still another example, the SAEDP includes a pneumatic pad.\",\n \"Optionally, the vehicle includes a display on which the representation of the outside environment may be presented to the occupant.\",\n \"Optionally, the display is coupled to the inner side of the compartment.\",\n \"Optionally, the display is a flexible display.\",\n \"Various embodiments described herein include a processor and/or a computer.\",\n \"For example, the autonomous-driving control system may be implemented using a computer and generation of a representation of the outside environment is done using a processor or a computer.\",\n \"The following are some examples of various types of computers and/or processors that may be utilized in some of the embodiments described herein.\",\n \"FIG.\",\n \"31a and FIG.\",\n \"31b are schematic illustrations of possible embodiments for computers (400, 410) that are able to realize one or more of the embodiments discussed herein.\",\n \"The computer (400, 410) may be implemented in various ways, such as, but not limited to, a server, a client, a personal computer, a network device, a handheld device (e.g., a smartphone), and/or any other computer form capable of executing a set of computer instructions.\",\n \"The computer 400 includes one or more of the following components: processor 401, memory 402, computer readable medium 403, user interface 404, communication interface 405, and bus 406.In one example, the processor 401 may include one or more of the following components: a general-purpose processing device, a microprocessor, a central processing unit, a complex instruction set computing (CISC) microprocessor, a reduced instruction set computing (RISC) microprocessor, a very long instruction word (VLIW) microprocessor, a special-purpose processing device, an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), a digital signal processor (DSP), a distributed processing entity, and/or a network processor.\",\n \"Continuing the example, the memory 402 may include one or more of the following memory components: CPU cache, main memory, read-only memory (ROM), dynamic random access memory (DRAM) such as synchronous DRAM (SDRAM), flash memory, static random access memory (SRAM), and/or a data storage device.\",\n \"The processor 401 and the one or more memory components may communicate with each other via a bus, such as bus 406.The computer 410 includes one or more of the following components: processor 411, memory 412, and communication interface 413.In one example, the processor 411 may include one or more of the following components: a general-purpose processing device, a microprocessor, a central processing unit, a complex instruction set computing (CISC) microprocessor, a reduced instruction set computing (RISC) microprocessor, a very long instruction word (VLIW) microprocessor, a special-purpose processing device, an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), a digital signal processor (DSP), a distributed processing entity, and/or a network processor.\",\n \"Continuing the example, the memory 412 may include one or more of the following memory components: CPU cache, main memory, read-only memory (ROM), dynamic random access memory (DRAM) such as synchronous DRAM (SDRAM), flash memory, static random access memory (SRAM), and/or a data storage device Still continuing the examples, the communication interface (405,413) may include one or more components for connecting to one or more of the following: an inter-vehicle network, Ethernet, intranet, the Internet, a fiber communication network, a wired communication network, and/or a wireless communication network.\",\n \"Optionally, the communication interface (405,413) is used to connect with the network 408.Additionally or alternatively, the communication interface 405 may be used to connect to other networks and/or other communication interfaces.\",\n \"Still continuing the example, the user interface 404 may include one or more of the following components: (i) an image generation device, such as a video display, an augmented reality system, a virtual reality system, and/or a mixed reality system, (ii) an audio generation device, such as one or more speakers, (iii) an input device, such as a keyboard, a mouse, an electronic pen, a gesture based input device that may be active or passive, and/or a brain-computer interface.\",\n \"It is to be noted that when a processor (computer) is disclosed in one embodiment, the scope of the embodiment is intended to also cover the use of multiple processors (computers).\",\n \"Additionally, in some embodiments, a processor and/or computer disclosed in an embodiment may be part of the vehicle, while in other embodiments, the processor and/or computer may be separate of the vehicle.\",\n \"For example, the processor and/or computer may be in a device carried by the occupant and/or remote of the vehicle (e.g., a server).\",\n \"As used herein, references to “one embodiment” (and its variations) mean that the feature being referred to may be included in at least one embodiment of the invention.\",\n \"Moreover, separate references to “one embodiment”, “some embodiments”, “another embodiment”, “still another embodiment”, etc., may refer to the same embodiment, may illustrate different aspects of an embodiment, and/or may refer to different embodiments.\",\n \"Some embodiments may be described using the verb “indicating”, the adjective “indicative”, and/or using variations thereof.\",\n \"Herein, sentences in the form of “X is indicative of Y” mean that X includes information correlated with Y, up to the case where X equals Y. Additionally, sentences in the form of “provide/receive an indication indicating whether X happened” refer herein to any indication method, including but not limited to: sending/receiving a signal when X happened and not sending/receiving a signal when X did not happen, not sending/receiving a signal when X happened and sending/receiving a signal when X did not happen, and/or sending/receiving a first signal when X happened and sending/receiving a second signal X did not happen.\",\n \"Herein, “most” of something is defined herein as above 51% of the something (including 100% of the something).\",\n \"A “portion” of something refers herein to 0.1% to 100% of the something (including 100% of the something).\",\n \"Sentences of the form “a portion of an area” refer herein to 0.1% to 100% percent of the area.\",\n \"As used herein, the terms “comprises,” “comprising,” “includes,” “including,” “has,” “having”, or any other variation thereof, indicate an open claim language that does not exclude additional limitations.\",\n \"The “a” or “an” is employed to describe one or more, and the singular also includes the plural unless it is obvious that it is meant otherwise.\",\n \"Certain features of some of the embodiments, which may have been, for clarity, described in the context of separate embodiments, may also be provided in various combinations in a single embodiment.\",\n \"Conversely, various features of some of the embodiments, which may have been, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-combination.\",\n \"Embodiments described in conjunction with specific examples are presented by way of example, and not limitation.\",\n \"Moreover, it is evident that many alternatives, modifications, and variations will be apparent to those skilled in the art.\",\n \"It is to be understood that other embodiments may be utilized and structural changes may be made without departing from the scope of the appended claims and their equivalents.\"\n ]\n]"},"source":{"kind":"string","value":"Patent_15871980"}}},{"rowIdx":4493970,"cells":{"text":{"kind":"list like","value":[["Micro Elements Transfer Device and Method","A transfer device for micro element with a test circuit can test the micro element during transfer.","The transfer device for micro elements includes: a base substrate, having two surfaces opposite to each other; a pick-up head array, formed over the first surface of the base substrate for picking up or releasing the micro element; a test circuit set inside or/on the surface of the base substrate, which has a series of sub-test circuits, each sub-test circuit at least having two test electrodes for simultaneous test of photoelectric parameters of the micro element when the transfer device transfers the micro element."],["1.A transfer device of micro element comprising: a base substrate, having two surfaces opposite to each other; a pick-up head array, formed over the first surface of the base substrate for picking up or releasing the micro element; and a test circuit set inside or/on the surface of the base substrate, which has a series of sub-test circuits, each sub-test circuit at least having two test electrodes for simultaneous test of photoelectric parameters of the micro element when the transfer device transfers the micro element.","2.The transfer device of claim 1, wherein: at least one test electrode of each sub-test circuit is formed over the surface of the pick-up head for contacting with the micro element, and connects to the micro element electrode when the pick-up head array contacts with the micro element.","3.The transfer device of claim 2, wherein: each sub-test circuit has a pair of test electrodes respectively.","4.The transfer device of claim 2, wherein: each sub-test circuit shares a test electrode.","5.The transfer device of claim 2, wherein: the test circuit also comprises a retractable electrode located on the first surface of the base substrate, which forms a sub-test circuit together with the test electrode formed over the surface of the pick-up head for contacting with the micro element.","6.The transfer device of claim 1, wherein: the transfer device also comprises a CMOS integrated circuit over the second surface of the base substrate, which connects to the test circuit.","7.The transfer device of claim 6, wherein: the base substrate has a through-hole structure, wherein, the test circuit passes through the through-hole structure and extends to the second surface of the base substrate.","8.The transfer device of claim 6, wherein: the base substrate is a Si substrate, and the CMOS integrated circuit is formed by a portion of the Si substrate.","9.The transfer device of claim 6, wherein: the CMOS integrated circuit is a structure layer formed over the base substrate.","10.The transfer device of claim 1, wherein: the pick-up head array picks up the micro element through electrostatic force, Van der Waals force and vacuum adsorption force.","11.The transfer device of claim 1, wherein: the pick-up head has a static electrode layer and a dielectric layer cladding on the electrode layer, wherein, when the electrode layer applies absorption voltage, the pick-up head produces static attraction force to pick up the micro element contact therewith.","12.The transfer device of claim 1, wherein: the surface of each pick-up head of the pick-up head array is made of biomimetic gecko material to absorb the micro element by virtue of absorption capacity of the biomimetic gecko material.","13.The transfer device of claim 1, wherein: the pick-up head array is a series of suction nozzle arrays, which absorb or release the micro element through vacuum pressure.","14.The transfer device of claim 13, wherein: the transfer device also comprises a cavity, a plurality of vacuum paths and a switch component, wherein, the suction nozzle array is connected to the cavity via a plurality of the vacuum paths, and valves are set at the connection place for switching on/off, and the switch component is used for controlling on or off of the valve of each vacuum path so that the suction nozzle is controlled to absorb or release required micro element through vacuum pressure.","15.The transfer device of claim 14, wherein: the switch component comprises a CMOS integrated circuit and an address electrode array connected to the CMOS integrated circuit, wherein, each vacuum path valve corresponds to the address electrode array.","16.The transfer device of claim 15, wherein: the valve is a movable member, wherein, the address electrode array is under selective excitation by the CMOS integrated circuit with voltage potential to generate electrostatic attraction, through which, corresponding movable member would deflect or approach to corresponding address electrode, thus controlling opening or closing of each vacuum path.","17.The transfer device of claim 14, wherein: the vacuum path is a series of micro-hole structures passing through the base substrate, wherein, one end is connected to the cavity, and the other is connected to the suction nozzle.","18.A transfer method of a micro element, the method comprising: (1) providing a transfer device, which comprises a base substrate, a pick-up head array formed over the surface of the base substrate and a test circuit inside or/and on the surface of the base substrate, wherein, the test circuit has a series of sub-test circuits, each sub-test circuit having at least two test electrodes; (2) positioning the transfer device on the micro element connected to the carrier substrate; and (3) contacting the test electrode of the transfer device with the micro element electrode to apply test voltage on the test circuit to form a test hoop for testing the micro element and obtaining defect pattern of the micro element of the carrier substrate.","19.The transfer method of claim 18, further comprising: (4) using the pick-up array of the transfer device to pick up qualified micro elements on the carrier substrate; (5) releasing micro elements on the acceptor substrate.","20.The transfer method of claim 18, further comprising: (4) using the pick-up array of the transfer device to pick up unqualified micro elements on the carrier substrate; (5) releasing unqualified micro elements on the acceptor substrate."],[" BACKGROUND Micro element technologies refer to integrate micro-size element arrays in high density over the substrate.","At present, the micro light emitting diode (Micro LED) technique is becoming a hot research topic, and the industry circle expects high-quality micro element products in the market.","High-quality micro light emitting diode products have profound impacts on conventional display products in the market, such as LCD/OLED.","During fabrication of the micro element, at first, a micro element is formed over the donor substrate, and then the micro element is transferred to the acceptor substrate.","For example, the acceptor substrate is a display screen."],[" SUMMARY The inventors of the present disclosure have recognized that, one difficulty during micro element fabrication is: how to transfer the micro element from the donor substrate to the acceptor substrate.","In conventional micro element transfer, the micro element is transferred to the acceptor substrate through a transfer substrate via wafer bonding.","Direct transfer is a kind of method by directly bonding the micro element array to the acceptor substrate from the transfer substrate, and then removing the transfer substrate.","Indirect transfer is the other method.","This method includes two times of bonding/lifting-off steps.","At first, the transfer substrate extracts the micro element array from the donor substrate, and bonds the micro element array to the acceptor substrate.","Finally, remove the transfer substrate.","The micro element array is generally extracted by electrostatic method.","During electrostatic extraction, a transfer head array is required.","Embodiments of the present disclosure provide a transfer device of micro element with a test circuit, to test micro elements and remove unqualified micro elements during transfer.","In an aspect: a transfer device of micro element is provided, including: a base substrate, having two surfaces opposite to each other; a pick-up head array, formed over the first surface of the base substrate for picking up or releasing the micro element; a test circuit set inside or/on the surface of the base substrate, which has a series of sub-test circuits, each sub-test circuit at least having two test electrodes for simultaneous test of photoelectric parameters of the micro element when the transfer device transfers the micro element.","In some embodiments, at least one test electrode of each sub-test circuit is formed over the surface of the pick-up head for contacting with the micro element, and for connecting the micro element electrode when the pick-up head array contacts with the micro element.","In some embodiments, the test circuit also comprises a retractable electrode located on the first surface of the base substrate, which forms a sub-test circuit together with the test electrode formed over the surface of the pick-up head for contacting with the micro element, which can be applied in micro elements with electrodes at different sides, such as a vertical micro light emitting diode.","In some embodiments, the transfer device also comprises a CMOS integrated circuit over the second surface of the base substrate, which connects to the test circuit.","In some embodiments, the base substrate has a through-hole structure, wherein, the test circuit passes through the through-hole structure and extends to the second surface of the base substrate.","In some embodiments, the base substrate is a Si substrate, and the CMOS integrated circuit is formed by a portion of the Si substrate.","In some embodiments, the CMOS integrated circuit is a structure layer formed over the base substrate.","In some embodiments, the pick-up head array picks up the micro element through electrostatic force, Van der Waals force and vacuum adsorption force.","In some embodiments, the pick-up head has a static electrode layer and a dielectric layer on the electrode layer, wherein, when the electrode layer applies absorption voltage, the pick-up head produces static attraction force to pick up the micro element contact therewith.","In some embodiments, the surface of each pick-up head of the pick-up head array is made of biomimetic gecko material to absorb the micro element by virtue of absorption capacity of the biomimetic gecko material.","In some embodiments, the pick-up head array is a series of suction nozzle arrays, which absorb or release the micro element through vacuum pressure.","In an embodiment, the transfer device also comprises a cavity, a plurality of vacuum paths and a switch component, wherein, the suction nozzle array is connected to the cavity via a plurality of vacuum paths, and valves are set at the connection place for switching on/off.","The switch component is used for controlling on or off of the valve of each vacuum path so that the suction nozzle is controlled to absorb or release required micro element through vacuum pressure.","In some embodiments, the switch component comprises a CMOS integrated circuit and an address electrode array connected to the CMOS integrated circuit, wherein, each vacuum path valve corresponds to the address electrode array.","In some embodiments, the valve is a movable member, wherein, the address electrode array is under selective excitation by the CMOS integrated circuit with voltage potential to generate electrostatic attraction, through which, corresponding movable member would deflect or approach to corresponding address electrode, thus controlling opening or closing of each vacuum path.","In some embodiments, the vacuum path is a series of micro-hole structures passing through the base substrate, wherein, one end is connected to the cavity, and the other is connected to the suction nozzle.","In some embodiments, the pick-up head size is below 100 μm, and the space is below 200 μm.","Various embodiments of the present disclosure also provide a transfer method for prior removal of micro element defects, comprising: providing a transfer device, which comprises a base substrate, a pick-up head array formed over the surface of the base substrate and a test circuit inside or/and on the surface of the base substrate, wherein, the test circuit has a series of sub-test circuits, each sub-test circuit having at least two test electrodes; positioning the transfer device on the micro element connected to the carrier substrate so that the test electrode contacts with the micro element; applying test voltage on the test circuit to form a test hoop for testing the micro element and obtaining defect pattern of the micro element of the carrier substrate.","In some embodiments, a transfer method for prior removal of micro element defects is disclosed, comprising: (1) providing a transfer device, which comprises a base substrate, a pick-up head array formed over the surface of the base substrate and a test circuit inside or/and on the surface of the base substrate, wherein, the test circuit has a series of sub-test circuits, each sub-test circuit having at least two test electrodes; (2) positioning the transfer device on the micro element connected to the carrier substrate; (3) contacting the test electrode with the micro element electrode, and applying test voltage on the test circuit to form a test hoop for testing the micro element and obtaining defect pattern of the micro element of the carrier substrate; (4) picking up qualified micro elements over the carrier substrate with the pick-up head array of the transfer device; and (5) releasing required micro elements on the acceptor substrate.","In some embodiments, a transfer method for prior removal of micro element defects is disclosed, comprising: (1) providing a transfer device, which comprises a base substrate, a pick-up head array formed over the surface of the base substrate and a test circuit inside or/and on the surface of the base substrate, wherein, the test circuit has a series of sub-test circuits, each sub-test circuit having at least two test electrodes; (2) positioning the transfer device on the micro element connected to the carrier substrate; (3) contacting the test electrode with the micro element electrode, and applying test voltage on the test circuit to form a test hoop for testing the micro element and obtaining defect pattern of the micro element of the carrier substrate; (4) picking up unqualified micro elements over the carrier substrate with the pick-up head array of the transfer device; and (5) releasing unqualified micro elements on the acceptor substrate.","In some embodiments, a transfer method for prior removal of micro element defects is disclosed, comprising: (1) providing a transfer device, which comprises a base substrate, a pick-up head array formed over the surface of the base substrate and a test circuit inside or/and on the surface of the base substrate, wherein, the test circuit has a series of sub-test circuits, each sub-test circuit having at least two test electrodes; (2) positioning the transfer device on the micro element connected to the carrier substrate; (3) contacting the test electrode with the micro element electrode, and applying test voltage on the test circuit to form a test hoop for testing the micro element and obtaining defect pattern of the micro element of the carrier substrate; (4) picking up micro elements over the carrier substrate with the pick-up head array of the transfer device; and (5) releasing unqualified and qualified micro elements onto different acceptor substrates respectively.","In some embodiments, a transfer method for prior removal of micro element defects is disclosed, comprising: (1) providing a transfer device, which comprises a base substrate, a pick-up head array formed over the surface of the base substrate and a test circuit inside or/and on the surface of the base substrate, wherein, the test circuit has a series of sub-test circuits, each sub-test circuit having at least two test electrodes; (2) positioning the transfer device on the micro element connected to the carrier substrate; (3) picking up the micro elements of the carrier substrate with the pick-up head array of the transfer device; (4) releasing the micro elements on the first acceptor substrate; (5) contacting the test electrode of the transfer device with the micro element electrode, and applying test voltage on the test circuit to form a test hoop for testing the micro element and obtaining defect pattern of the micro element of the first acceptor substrate; (6) picking up unqualified micro elements on the first acceptor substrate with the pick-up head array of the transfer device; and (7) releasing unqualified micro elements on the second acceptor substrate.","In some embodiments, the pick-up head array can pick up the micro element through electrostatic force, Van der Waals force and vacuum adsorption force.","According to another embodiment of the present invention, a method for fabricating a micro element device is provided, comprising the transfer of the micro element to the receiving substrate of the micro element device through the method disclosed in the present invention.","According to another embodiment of the present invention, a micro element device fabricated according to the method disclosed in the present invention is provided.","According to another embodiment of the present invention, an electronic device comprising the micro element device of the present invention is provided.","In some embodiments, the method above can further include: (4) using the pick-up array of the transfer device to pick up micro elements on the carrier substrate; (5) releasing unqualified and qualified micro elements on different acceptor substrates.","In another aspect, a transfer method of micro element is provided, the method including: (1) providing a transfer device, which comprises a base substrate, a pick-up head array formed over the surface of the base substrate and a test circuit inside or/and on the surface of the base substrate, wherein, the test circuit has a series of sub-test circuits, each sub-test circuit having at least two test electrodes; (2) positioning the transfer device on the micro element connected to the carrier substrate; (3) using the pick-up array of the transfer device to pick up micro elements on the carrier substrate; (4) releasing micro elements on the first acceptor substrate; (5) contacting the test electrode of the transfer device with the micro element electrode to apply test voltage on the test circuit to form a test loop for testing the micro element and obtaining defect pattern of the micro element of the first acceptor substrate; (6) using the pick-up array of the transfer device to pick up unqualified micro elements on the first acceptor substrate; (7) releasing unqualified micro elements on the second acceptor substrate.","In another aspect, a method for fabricating a micro element device, is provided, including any of micro element transfer method with prior removal of defects as described above.","In another aspect, a micro element device fabricated according to the method above is provided.","In another aspect, an electronic device including the micro element device described above is provided.","The other features and advantages of this present disclosure will be described in detail in the following specification, and it is believed that such features and advantages will become more obvious in the specification or through implementations of this invention.","The purposes and other advantages of the present disclosure can be realized and obtained in the structures specifically described in the specifications, claims and drawings.","In addition, it should be understood by those skilled in the art that despite many problems in the prior art, the technical scheme of each embodiment or claim of the present invention can be improved in one or several aspects.","It is not necessary to solve all technical problems listed in the prior art or the background art.","It should be understood by those skilled in the art that contents not mentioned in a claim shall not be construed as limiting the claim."],["CROSS-REFERENCE TO RELATED APPLICATIONS The present application is a continuation of, and claims priority to, PCT/CN2016/104869 filed on Nov. 7, 2016, which claims priority to Chinese Patent Application No.","201610961364.5 filed on Nov. 4, 2016.The disclosures of these applications are hereby incorporated by reference in their entirety.","BACKGROUND Micro element technologies refer to integrate micro-size element arrays in high density over the substrate.","At present, the micro light emitting diode (Micro LED) technique is becoming a hot research topic, and the industry circle expects high-quality micro element products in the market.","High-quality micro light emitting diode products have profound impacts on conventional display products in the market, such as LCD/OLED.","During fabrication of the micro element, at first, a micro element is formed over the donor substrate, and then the micro element is transferred to the acceptor substrate.","For example, the acceptor substrate is a display screen.","SUMMARY The inventors of the present disclosure have recognized that, one difficulty during micro element fabrication is: how to transfer the micro element from the donor substrate to the acceptor substrate.","In conventional micro element transfer, the micro element is transferred to the acceptor substrate through a transfer substrate via wafer bonding.","Direct transfer is a kind of method by directly bonding the micro element array to the acceptor substrate from the transfer substrate, and then removing the transfer substrate.","Indirect transfer is the other method.","This method includes two times of bonding/lifting-off steps.","At first, the transfer substrate extracts the micro element array from the donor substrate, and bonds the micro element array to the acceptor substrate.","Finally, remove the transfer substrate.","The micro element array is generally extracted by electrostatic method.","During electrostatic extraction, a transfer head array is required.","Embodiments of the present disclosure provide a transfer device of micro element with a test circuit, to test micro elements and remove unqualified micro elements during transfer.","In an aspect: a transfer device of micro element is provided, including: a base substrate, having two surfaces opposite to each other; a pick-up head array, formed over the first surface of the base substrate for picking up or releasing the micro element; a test circuit set inside or/on the surface of the base substrate, which has a series of sub-test circuits, each sub-test circuit at least having two test electrodes for simultaneous test of photoelectric parameters of the micro element when the transfer device transfers the micro element.","In some embodiments, at least one test electrode of each sub-test circuit is formed over the surface of the pick-up head for contacting with the micro element, and for connecting the micro element electrode when the pick-up head array contacts with the micro element.","In some embodiments, the test circuit also comprises a retractable electrode located on the first surface of the base substrate, which forms a sub-test circuit together with the test electrode formed over the surface of the pick-up head for contacting with the micro element, which can be applied in micro elements with electrodes at different sides, such as a vertical micro light emitting diode.","In some embodiments, the transfer device also comprises a CMOS integrated circuit over the second surface of the base substrate, which connects to the test circuit.","In some embodiments, the base substrate has a through-hole structure, wherein, the test circuit passes through the through-hole structure and extends to the second surface of the base substrate.","In some embodiments, the base substrate is a Si substrate, and the CMOS integrated circuit is formed by a portion of the Si substrate.","In some embodiments, the CMOS integrated circuit is a structure layer formed over the base substrate.","In some embodiments, the pick-up head array picks up the micro element through electrostatic force, Van der Waals force and vacuum adsorption force.","In some embodiments, the pick-up head has a static electrode layer and a dielectric layer on the electrode layer, wherein, when the electrode layer applies absorption voltage, the pick-up head produces static attraction force to pick up the micro element contact therewith.","In some embodiments, the surface of each pick-up head of the pick-up head array is made of biomimetic gecko material to absorb the micro element by virtue of absorption capacity of the biomimetic gecko material.","In some embodiments, the pick-up head array is a series of suction nozzle arrays, which absorb or release the micro element through vacuum pressure.","In an embodiment, the transfer device also comprises a cavity, a plurality of vacuum paths and a switch component, wherein, the suction nozzle array is connected to the cavity via a plurality of vacuum paths, and valves are set at the connection place for switching on/off.","The switch component is used for controlling on or off of the valve of each vacuum path so that the suction nozzle is controlled to absorb or release required micro element through vacuum pressure.","In some embodiments, the switch component comprises a CMOS integrated circuit and an address electrode array connected to the CMOS integrated circuit, wherein, each vacuum path valve corresponds to the address electrode array.","In some embodiments, the valve is a movable member, wherein, the address electrode array is under selective excitation by the CMOS integrated circuit with voltage potential to generate electrostatic attraction, through which, corresponding movable member would deflect or approach to corresponding address electrode, thus controlling opening or closing of each vacuum path.","In some embodiments, the vacuum path is a series of micro-hole structures passing through the base substrate, wherein, one end is connected to the cavity, and the other is connected to the suction nozzle.","In some embodiments, the pick-up head size is below 100 μm, and the space is below 200 μm.","Various embodiments of the present disclosure also provide a transfer method for prior removal of micro element defects, comprising: providing a transfer device, which comprises a base substrate, a pick-up head array formed over the surface of the base substrate and a test circuit inside or/and on the surface of the base substrate, wherein, the test circuit has a series of sub-test circuits, each sub-test circuit having at least two test electrodes; positioning the transfer device on the micro element connected to the carrier substrate so that the test electrode contacts with the micro element; applying test voltage on the test circuit to form a test hoop for testing the micro element and obtaining defect pattern of the micro element of the carrier substrate.","In some embodiments, a transfer method for prior removal of micro element defects is disclosed, comprising: (1) providing a transfer device, which comprises a base substrate, a pick-up head array formed over the surface of the base substrate and a test circuit inside or/and on the surface of the base substrate, wherein, the test circuit has a series of sub-test circuits, each sub-test circuit having at least two test electrodes; (2) positioning the transfer device on the micro element connected to the carrier substrate; (3) contacting the test electrode with the micro element electrode, and applying test voltage on the test circuit to form a test hoop for testing the micro element and obtaining defect pattern of the micro element of the carrier substrate; (4) picking up qualified micro elements over the carrier substrate with the pick-up head array of the transfer device; and (5) releasing required micro elements on the acceptor substrate.","In some embodiments, a transfer method for prior removal of micro element defects is disclosed, comprising: (1) providing a transfer device, which comprises a base substrate, a pick-up head array formed over the surface of the base substrate and a test circuit inside or/and on the surface of the base substrate, wherein, the test circuit has a series of sub-test circuits, each sub-test circuit having at least two test electrodes; (2) positioning the transfer device on the micro element connected to the carrier substrate; (3) contacting the test electrode with the micro element electrode, and applying test voltage on the test circuit to form a test hoop for testing the micro element and obtaining defect pattern of the micro element of the carrier substrate; (4) picking up unqualified micro elements over the carrier substrate with the pick-up head array of the transfer device; and (5) releasing unqualified micro elements on the acceptor substrate.","In some embodiments, a transfer method for prior removal of micro element defects is disclosed, comprising: (1) providing a transfer device, which comprises a base substrate, a pick-up head array formed over the surface of the base substrate and a test circuit inside or/and on the surface of the base substrate, wherein, the test circuit has a series of sub-test circuits, each sub-test circuit having at least two test electrodes; (2) positioning the transfer device on the micro element connected to the carrier substrate; (3) contacting the test electrode with the micro element electrode, and applying test voltage on the test circuit to form a test hoop for testing the micro element and obtaining defect pattern of the micro element of the carrier substrate; (4) picking up micro elements over the carrier substrate with the pick-up head array of the transfer device; and (5) releasing unqualified and qualified micro elements onto different acceptor substrates respectively.","In some embodiments, a transfer method for prior removal of micro element defects is disclosed, comprising: (1) providing a transfer device, which comprises a base substrate, a pick-up head array formed over the surface of the base substrate and a test circuit inside or/and on the surface of the base substrate, wherein, the test circuit has a series of sub-test circuits, each sub-test circuit having at least two test electrodes; (2) positioning the transfer device on the micro element connected to the carrier substrate; (3) picking up the micro elements of the carrier substrate with the pick-up head array of the transfer device; (4) releasing the micro elements on the first acceptor substrate; (5) contacting the test electrode of the transfer device with the micro element electrode, and applying test voltage on the test circuit to form a test hoop for testing the micro element and obtaining defect pattern of the micro element of the first acceptor substrate; (6) picking up unqualified micro elements on the first acceptor substrate with the pick-up head array of the transfer device; and (7) releasing unqualified micro elements on the second acceptor substrate.","In some embodiments, the pick-up head array can pick up the micro element through electrostatic force, Van der Waals force and vacuum adsorption force.","According to another embodiment of the present invention, a method for fabricating a micro element device is provided, comprising the transfer of the micro element to the receiving substrate of the micro element device through the method disclosed in the present invention.","According to another embodiment of the present invention, a micro element device fabricated according to the method disclosed in the present invention is provided.","According to another embodiment of the present invention, an electronic device comprising the micro element device of the present invention is provided.","In some embodiments, the method above can further include: (4) using the pick-up array of the transfer device to pick up micro elements on the carrier substrate; (5) releasing unqualified and qualified micro elements on different acceptor substrates.","In another aspect, a transfer method of micro element is provided, the method including: (1) providing a transfer device, which comprises a base substrate, a pick-up head array formed over the surface of the base substrate and a test circuit inside or/and on the surface of the base substrate, wherein, the test circuit has a series of sub-test circuits, each sub-test circuit having at least two test electrodes; (2) positioning the transfer device on the micro element connected to the carrier substrate; (3) using the pick-up array of the transfer device to pick up micro elements on the carrier substrate; (4) releasing micro elements on the first acceptor substrate; (5) contacting the test electrode of the transfer device with the micro element electrode to apply test voltage on the test circuit to form a test loop for testing the micro element and obtaining defect pattern of the micro element of the first acceptor substrate; (6) using the pick-up array of the transfer device to pick up unqualified micro elements on the first acceptor substrate; (7) releasing unqualified micro elements on the second acceptor substrate.","In another aspect, a method for fabricating a micro element device, is provided, including any of micro element transfer method with prior removal of defects as described above.","In another aspect, a micro element device fabricated according to the method above is provided.","In another aspect, an electronic device including the micro element device described above is provided.","The other features and advantages of this present disclosure will be described in detail in the following specification, and it is believed that such features and advantages will become more obvious in the specification or through implementations of this invention.","The purposes and other advantages of the present disclosure can be realized and obtained in the structures specifically described in the specifications, claims and drawings.","In addition, it should be understood by those skilled in the art that despite many problems in the prior art, the technical scheme of each embodiment or claim of the present invention can be improved in one or several aspects.","It is not necessary to solve all technical problems listed in the prior art or the background art.","It should be understood by those skilled in the art that contents not mentioned in a claim shall not be construed as limiting the claim.","BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings, which are included to provide a further understanding of the invention and constitute a part of this specification, together with the embodiments, are therefore to be considered in all respects as illustrative and not restrictive.","In addition, the drawings are merely illustrative, which are not drawn to scale.","FIG.","1 is a side sectional view of a transfer device of micro element according to a first embodiment of the present disclosure.","FIG.","2 is a schematic diagram showing that voltage is applied on the electrode layer of the pick-up head of the transfer device as shown in FIG.","1 to produce statistic absorption force.","FIG.","3 is a schematic diagram showing that voltage is applied on the test circuit of the transfer device as shown in FIG.","1 to form a test hoop.","FIG.","4 is a side sectional view of a transfer device of micro element according to a second embodiment of the present disclosure.","FIG.","5 is a schematic diagram showing that voltage is applied on the test circuit of the transfer device as shown in FIG.","4 to test the micro element.","FIG.","6 is a schematic diagram showing that voltage is applied on the electrode layer of the pick-up head of the transfer device as shown in FIG.","4 to produce statistic absorption force.","FIG.","7 is a side sectional view of a transfer device of micro element according to a third embodiment of the present disclosure.","FIG.","8 is a schematic diagram showing that voltage is applied on the test circuit of the transfer device as shown in FIG.","7 to test the micro element.","FIG.","9 is a schematic diagram showing that voltage is applied on the electrode layer of the pick-up head of the transfer device as shown in FIG.","7 to produce statistic absorption force.","FIG.","10 is a side sectional view of a transfer device of micro element according to a fourth preferred embodiment, wherein the surface of the pick-up head 4120 has a micro nanometer-composite rigid villi structure.","FIG.","11 is a SEM diagram of the rigid villi structure of the micro element transfer device as shown in FIG.","10.FIG.","12 is a side section view of a transfer device of micro element according to a fifth preferred embodiment.","FIG.","13 is a first schematic diagram illustrating the vacuum path valve of the micro element the transfer device.","FIG.","14 is a second schematic diagram illustrating the vacuum path valve of the micro element the transfer device.","FIG.","15 is a third schematic diagram illustrating the vacuum path valve of the micro element the transfer device.","FIG.","16 is a cross-section view of FIG.","14 along line A-A.","FIG.","17 is a cross-sectional view of FIG.","14 along line B-B, in which the vacuum path is OFF.","FIG.","18 is a cross-sectional view of FIG.","14 along line B-B, in which the vacuum path is ON.","FIG.","19 is a flow chart illustrating prior removal of defects of a micro element during transfer according to the present invention.","FIG.","20 is a flow chart illustrating the transfer method of the micro element according to a sixth preferred embodiment.","FIG.","21 illustrates a first step of the transfer method of the micro element according to the sixth embodiment.","FIG.","22 illustrates a second step of the transfer method of the micro element according to the sixth embodiment.","FIG.","23 illustrates a third step of the transfer method of the micro element according to the sixth embodiment.","FIG.","24 illustrates a fourth step of the transfer method of the micro element according to the sixth embodiment.","FIG.","25 is flow chart illustrating the transfer method of the micro element according to a seventh embodiment.","FIG.","26 illustrates a first step of the transfer method of the micro element according to the seventh embodiment.","FIG.","27 illustrates a second step of the transfer method of the micro element according to the seventh embodiment.","FIG.","28 is flow chart illustrating the transfer method of the micro element according to an eighth embodiment.","FIG.","29 illustrates a first step of the transfer method of the micro element according to the eighth embodiment.","FIG.","30 illustrates a second step of the transfer method of the micro element according to the eighth embodiment.","FIG.","31 illustrates a third step of the transfer method of the micro element according to the eighth embodiment.","FIG.","32 is a flow chart illustrating the transfer method of the micro element according to a ninth embodiment.","FIG.","33 illustrates a first step of the transfer method of the micro element according to the ninth embodiment.","FIG.","34 illustrates a second step of the transfer method of the micro element according to the ninth embodiment.","FIG.","35 illustrates a third step of the transfer method of the micro element according to the ninth embodiment.","FIG.","36 illustrates a fourth step of the transfer method of the micro element according to the ninth embodiment.","FIG.","37 illustrates a fifth step of the transfer method of the micro element according to the ninth embodiment.","In the drawings: 1100, 2100, 3100, 4100, 5100: transfer device; 1110, 2110, 3110, 4110, 5110: base substrate; 1110A: first surface of the base substrate; 1110B: second surface of the base substrate; 1120, 2120, 3120, 4120, 5120: pick-up head; 1120A: surface of the pick-up head for contacting with the micro element; 1122, 2122, 3122: electrostatic circuit connecting line of the pick-up head; 1124, 2124, 3124: electrode layer of the pick-up head; 1126, 2126, 3126: dielectric layer; 1132A, 1132B, 2132A, 2132B, 3132, 4132A, 4132B, 5132A, 5132B: circuit; 1134A, 1134B, 2134A, 2134B, 3134, 4134A, 4134B, 5134A, 5134B: test electrode; 2136, 3136: retractable electrode; 1140, 2140, 3140, 4140: CMOS integrated circuit; 1200, 2200, 3200: micro element; 1220A, 1220B, 3220: micro element electrode; 1300, 2300, 3300: carrier substrate; 1310, 2310, 3310: middle layer; 1140, 2140, 3140, 4140: CMOS integrated circuit; 5138: insulating protective layer; 5150: through hole/vacuum path; 5152: valve/movable member; 5154: carrier layer; 5160: cavity; 5170: CMOS integrated circuit; 5172: address electrode layer; 5174: address electrode.","DETAILED DESCRIPTION This embodiment describes a micro element transfer device and method for transferring a micro element with the transfer device.","The micro element array can be a micro LED device, a diode, a transistor, an integrated chip (IC), with size of 1-100 μm, which is not limited to this size.","In addition, some aspects of the embodiment may apply to larger or smaller sizes.","The embodiments below describe a micro element transfer device and method for transferring a micro element with the transfer device.","The transfer device has a pick-up head array for picking up or releasing the micro element, and size (such as length or width) of each pick-up head is 1-100 μm.","The transfer device also has a test circuit, and each pick-up head corresponds to a sub-test circuit.","When the pick-up head contacts with the micro element, voltage is applied on the test circuit to form a test hoop for photoelectric performance test of the micro element.","Therefore, defect pattern of the defect micro element is obtained to remove defect micro elements during micro element array transfer.","FIG.","1 is a side section view of a transfer device according to the first preferred embodiment of the present invention.","The transfer device 1100 comprises: a base substrate 1110, an array of pick-up head 1120, a test circuit and a CMOS integrated circuit 1140.Specifically, the base substrate 1110 is for supporting, which can be made of a variety of materials, such as Si, ceramics and polymer.","The pick-up head 1120 is formed over the first surface 1110A of the base substrate 1110 in an array arrangement.","The size range is 1 μm-100 μm, and the size, for example, can be 50 μm-20 μm.","The pitch is (1 μm-100 μm)×(1 μm-100 μm), such as 10 μm×10 μm or 50 μm×100 μm.","The array of pick-up head 1120 is located on the first surface 1110A of the base substrate 1100 for picking up the micro element through various adsorption forces (such as electrostatic force, vacuum pressure, Van der Waals force, magnetic force and the like) for print transfer.","In some embodiments, each pick-up head can be independently controllable for selective pick-up and release of the micro element.","The test circuit is composed of a series of sub-test circuits, each sub-test circuit corresponding to a pick-up head 1120, and having at least two test electrodes 1134A and 1134B, wherein, the sub-test circuit is connected to the working electronic device of the test module such as CMOS integrated circuit 1140 via the circuits 1132A and 1132B.","In this embodiment, the array of pick-up head 1120 picks up and releases the micro element through electrostatic force, wherein, each pick-up head 1120 corresponds to an electrostatic adsorption circuit, comprising a connection circuit 1122 and an electrode layer 1124, wherein, the connection line 1122 can go through the base substrate 1110, and connect to the CMOS integrated circuit 1140 so as to connect to external electronic control piece.","The surface of the electrode layer 1124 is covered with a dielectric layer 1126.Thus, when absorption voltage is applied on the electrode layer 1124, electrostatic adsorption force is formed to pick up the micro element, as shown in FIG.","2.The test circuit of the transfer device 1100 is composed of a series of sub-test circuits, and each pick-up head 1120 corresponds to a sub-test circuit, which is composed of test electrodes 1134A, 1134B and circuits 1132A, 1132B.","A pair of through-hole structures are formed at a place of the base substrate 1110 approaching the pick-up head 1120, and the through holes are filled with conductive materials to form circuits 1132A and 1132B to connect the test electrodes 1134A, 1134B to the CMOS integrated circuit 1140 on the second surface 1100B of the base substrate.","The test electrodes 1134A and 1134B are embedded in the dielectric layer 1126, and the lower surface is parallel with the lower surface of the dielectric layer 1126.At this time, the surface 1120A of the pick-up head 1120 for contacting with the micro element is composed of test electrodes 1134A, 1134B and the dielectric layer 1126, as shown in FIG.","1.When the surface 1120A of the pick-up head 1120 contacts with the micro element, the test electrode 1134A contacts with the micro element electrode 1220A, and the test electrode 1134B contacts with the micro element electrode 1220B.","The transfer device 1100 of this embodiment mainly targets at micro elements 1200 with electrodes at same side (for example, micro light emitting diode with electrodes at same side), and the test electrodes 1134A and 1134B are formed on the surface 1120A of the pick-up head 1120 for contacting with the micro element.","Before transferring the micro element 1200 with the transfer device 1100, the micro element 1200 is generally placed on the carrier substrate 1300 (a middle layer 1310 can be set between them, but is not necessarily required), wherein, electrodes 1220A and 1220B are generally placed upwards.","When the pick-up head 1120 of the transfer device 1100 aligns with the contact micro element 1200, the test electrode 1134A contacts with the micro element electrode 1220A, and the test electrode 1134B contacts with the micro element electrode 1220B.","When test voltage is applied on test electrodes 1134A and 1134B through circuits 1132A and 1132B, a test hoop is formed, as shown in FIG.","3 to realize photoelectric parameter test for the micro element.","Thus, the micro elements are tested during transferring for prior removal of defect micro elements.","FIG.","4 is a side section view of a transfer device according to the second preferred embodiment of the present invention.","Different from the transfer device 1100, the transfer device 2100 also has at least a retractable electrode 2136, which forms a sub-test circuit together with the test electrode 2134B formed over the surface of the pick-up head for contacting with the micro element, which can be applied for micro elements with electrodes at different sides, such as a vertical micro light emitting diode.","The retractable electrode 2136 and the pick-up head 2120 are at the same side, which can be located outside the array of the pick-up head 2120, and the lower end 2136A extrudes the lower end 2120A of the pick-up head 2120.When the transfer device 2100 is used for transferring the vertical micro element, the vertical micro element 2200 is placed on the conductive carrier substrate 2300, and the pick-up head 2120 of the transfer device 2100 orients to and contacts with the micro element 2200, then the test electrode 2034B contacts with the top electrode 2220 of the micro element 2200, and the retractable electrode 2136 contacts with the carrier substrate 2300.FIGS.","5 and 6 show circuit connections under the test mode and the pick-up mode.","Referring to FIG.","5, when the transfer device 2100 tests the micro element, test voltage connects the test electrode 2134B and the retractable electrode 2136, wherein, 2134B connects the top electrode 2220 of the micro element, and the retractable electrode 2136 connects the conductive substrate 2300 to form a test hoop to realize test for the micro element 2200; referring to FIG.","6, when the transfer device 2100 picks up the micro element, when the absorption voltage connects the electrode layer 2124 of the electrostatic circuit, static attraction force is generated on the surface of the pick-up head 2120 to pick up the micro element contacted therewith.","The transfer device of the embodiment can be used for testing and transfer printing of micro elements with electrodes at same or different sides (namely, the vertical micro element).","When the transfer device is applied for transferring the vertical micro element, the test electrode 2134B and the retractable electrode 2136 form a test circuit; when the transfer device is applied for transferring horizontal micro elements, the test electrodes 2134B and 2134A form a test circuit.","The retractable electrode 2136 can be used for electrostatic protection.","FIG.","7 is a side section view of a transfer device according to the third preferred embodiment of the present invention.","Different from the transfer device 2100, the transfer device 3100 is mainly applied for vertical micro elements.","In this embodiment, the test circuit is simplified as only one test electrode 3134 forms on the surface of the pick-up head 3120.FIGS.","8 and 9 show circuit connections under the test mode and the pick-up mode.","Referring to FIG.","8, when the transfer device 3100 tests the micro element, the test voltage connects the test electrode 3134 and the retractable electrode 3136, wherein, the test electrode 3134 connects the top surface electrode 3220 of the micro element, and the retractable electrode 3136 connects to the conductive carrier substrate 3300 to form a test hoop for testing the micro element 3200; referring to FIG.","9, when the transfer device 2100 picks up the micro element 3200, one end of the external power is directly grounded, and the other end connects to the electrode layer 3124.Static attraction force is produced on the surface of the pick-up head 3120 to pick up the micro element contact therewith.","FIG.","10 is a side section view of a transfer device according to the fourth preferred embodiment of the present invention.","Different from the transfer device 1100, the pick-up head 4120 of the transfer device 4100 picks up and releases the micro element with Van der Waals force.","In this embodiment, the surface of the pick-up head 4120 is made of biomimetic gecko.","When it orients to and contacts with the micro element, the pick-up head absorbs the micro element by virtue of absorption capacity of the biomimetic gecko to pick up required micro element, and desorbs the micro element by virtue of desorption capacity the biomimetic gecko to release the micro element.","In this embodiment, the test electrodes 4314A and 4134B are not necessarily to cover the surface of the pick-up head 4120, but to expose part of the test electrode on the surface of the pick-up head for contacting with the micro element to the extent that the test electrode can be connected to the micro element electrode when the pick-up head 4120 contacts the micro element.","Specifically, the pick-up head 4120 is made of biomimetic gecko material, which can be silicone rubber, polyurethane, multiwalled carbon nanotube, polyester resin, polyimide, artificial rubber, epoxy resin, polydimethylsiloxane, polyurethane and ethylene glycol terephthalate or polymethyl methacrylate or any of their combinations.","Further, the surface of the pick-up head 4120 comprises micro nanometer-composite rigid villi structure, as shown in FIG.","11, for example, with protrusion density of 1×105-6×108 protrusions per cm2.Van der Waals force is produced when the rigid villi structure made of biomimetic gecko material contacts with the micro element surface with adhesive attraction, which absorbs the micro element to pick up the micro element.","In some embodiments, the surface of the rigid villi structure has hydrophobic nature, which prevents water layer from being formed on the contact surface, which eliminates possible function of capillary force as much as possible, thus playing an important role for narrowing gap and providing Van der Waals force.","FIG.","12 is a side section view of a transfer device according to the fifth preferred embodiment of the present invention.","Different from the transfer device 1100, the pick-up head 5120 of the transfer device 5100 is a suction nozzle structure, which picks up and releases the micro element through vacuum pressure adsorption.","Specifically, the transfer device 5100 has a suction nozzle array.","Each suction nozzle is connected to a same cavity 5160 through the vacuum path 5150, and each vacuum path has a valve 5152 to control ON/OFF of the vacuum path.","Size (for example length or width) of each suction nozzle is 1-100 μm.","Each suction nozzle is 1-20 μm.","Pitch of the suction nozzle array is (1 μm-100 μm)×(1 μm-100 μm), for example 10 μm×10 μm or 50 μm×100 μm.","To reach such size, each vacuum path can be a series of micro-hole structures formed over the base substrate 5110 (such as Si substrate).","Correspondingly, each suction nozzle 5120 corresponds to a vacuum path 5150, a valve 5152 and a switch element.","A CMOS storage circuit and an address electrode array can be used for providing the switch array with micro size.","Digital micro-mirror device (DMD) is a single chip semiconductor device with micro electro mechanical system (MEMS), which generally comprises area arrays of bistable state movable micro-mirror for forming image elements (pixel).","The micro-mirror is fabricated in the area array corresponding to the addressing memory unit and placed above related address electrode at the bottom of the micro-mirror, wherein, the address electrode is under selective excitation by the control circuit to generate electrostatic attraction causing corresponding micro-mirror to deflect towards corresponding address electrode.","The embodiments, with the principle of DMD chip, a movable member of a micro-mirror similar to the DMD chip is set at the connection position of each vacuum path and the shared cavity, as a valve, and an associated address electrode is fabricated above the movable member, wherein, the address electrode is under selective excitation by the control circuit to generate electrostatic attraction causing corresponding movable member to deflect towards corresponding address electrode.","In this way, the movable member skews or deflects to the address electrode to close or open the vacuum path, and controls each vacuum path valve via the switching component for controlling opening or closing of the vacuum path to extract required micro element.","Referring to FIG.","12, the transfer device 5100 comprises a base substrate 5110, a cavity 5160 above the base substrate 5110 and a switch array above the cavity 5160.Specifically, the base substrate 5110 has an array of through hole 5150, and a series of suction nozzle structures are formed at the bottom surface of the base substrate 5110 to serve as the pick-up head 5120.Conductive layers 5132A and 5132B are formed at the side wall of the through hole 5150, and extend towards the upper and lower surfaces of the base substrate 5110.Test electrode 5134A and 5134B are formed on the lower surface of the base substrate 5110.Cover a dielectric layer over the conductive layers 5132A and 5132B as the insulating protective layer 5138.The conductive layers 5132A, 5132B and the test electrodes 5134A, 5134B form a test circuit, wherein, a functional circuit (such as a CMOS integrated circuit, not shown) can be formed inside the base substrate 5110 for connecting the test circuit.","In this embodiment, each suction nozzle 5120 is connected to a same cavity 5160 through the through hole 5150.As the vacuum path, each through hole 5150 is used for transmitting vacuum pressure so that the suction nozzle 5120 can absorb or release the micro element through vacuum pressure.","Further, a valve 5152 is set at the opening of each through hole 5150 for controlling ON/OFF of each vacuum path 5150.The valve of each vacuum path is controlled by the switch component so as to control ON or OFF of the vacuum path to pick up required micro element.","The switch array is composed of a CMOS storage circuit layer 5170 and an address electrode layer 5172 thereunder, wherein, the address electrode layer 5172 is provided with an array of address electrode 5174, each address electrode 5174 corresponding to a vacuum path 5150.In this embodiment, the valve 5152 is a member 5152 capable for deflection at the micro hole structure, wherein, the edge of this member is not connected to the through hole edge, but connects to the base substrate 5110 with a carrier layer 5154.Under electrostatic attraction of the address electrode 5174, the member 5152 deflects taking the pivot as the center, wherein, one end deflects towards the address electrode 5174.FIGS.","13-15 are schematic diagrams of the vacuum path valve.","The valve structure comprises a carrier layer 5154 on the surface of the base substrate 5110 and a movable member 5152 on the carrier layer 5154.The carrier layer 5154 comprises a frame 5154a, a pivot 5154b and an opening 5154c, wherein, the pivot 5154b is supported on the frame 5154a and cross the opening 5154c.","The movable member 5152 is supported on the pivot 5154b through the hole 5152a, and can deflect or decline taking the pivot 5154b as the center.","FIGS.","16-18 are section views of each suction nozzle of the transfer device.","FIG.","16 is a schematic diagram along line A-A of FIG.","14.As shown in the figure, in this embodiment, the upper surface of the pivot 5154b is lower than the frame 5154a, and the component 5152 suspends on the pivot 5154b.","FIGS.","17-18 are schematic diagrams along line A-A of FIG.","12.As shown in the figure, an address electrode 5174 is arranged above the member 5152.The CMOS memory circuit controls the ON/OFF status of the address electrode 5174.When the address electrode 5174 is in OFF status, the address electrode 5174 is not excited with voltage potential so as not to generate electrostatic attraction, and the member 5152 is not deflected, thus closing the vacuum path 5150, as shown in FIG.","17; when the address electrode 5174 is in ON status, the address electrode 5174 is excited with voltage potential to generate electrostatic attraction.","Under electrostatic attraction of the address electrode 5174, the edge of the member 5152 deflects on the pivot 5154b and deflects towards the address electrode 5174, thus opening the vacuum path 5150, as shown in FIG.","18.FIG.","19 is a flow diagram of defect removal of the micro element through any of the aforesaid transfer device, which can include steps S110-S130.Brief description is given below.","S110: provide any of the transfer devices.","The transfer device comprises a pick-up head array and a test circuit, wherein, the test circuit is composed of a series of sub-test electrodes, and each sub-test circuit corresponds to a pick-up head.","In some embodiments, in general, the device comprises two test electrodes, wherein, at least one test electrode is located over the surface of the pick-up head for contacting with the micro element, so that when the pick-up head contacts with the micro element, the test electrode injects test current to the micro element.","S120: position the transfer device on the micro element connected to the carrier substrate.","The carrier substrate can be a growth substrate or a carrier substrate; for example, the carrier substrate material can be glass, Si, polycarbonate (PC), acrylonitrile butadiene styrene (ABS) or any of their combination.","The micro element can be a micro light emitting diode, with thickness of about 0.5 μm to about 100 μm.","The micro element can be a cylinder with radius of about 0.5 μm to about 500 μm.","However, the micro element is not limited to cylinder, but can be triangular column, cube, rectangular, hexagonal column, octagonal column or other polygonal cylinders.","S130: contact the test electrode of the transfer device with the micro element electrode to apply test voltage on the test circuit to form a test hoop for testing the micro element and obtaining defect pattern of the micro element of the carrier substrate.","Through the test circuit of the transfer device, when the pick-up head array contacts with the micro element, the test electrode connects to the micro element electrode to form a test hoop.","During transferring of the micro element, test the micro element to obtain defect pattern of the micro element for selective pick-up of qualified micro elements or unqualified micro elements.","The embodiment for a transfer method of micro element for prior removal of defects is described in detail with reference to figures below.","FIG.","20 is a schematic diagram of a transfer method of the micro element according to the sixth preferred embodiment of the present invention, comprises steps S210-S250.For example, S210 includes provide a transfer device, including pick-up head array and test circuit, test circuit including a series of sub-test electrodes, each sub-test circuit having at least two test electrodes.","S220 includes positioning the transfer device on the micro element connected to the carrier substrate.","S230 includes contacting the test electrode of the transfer device with the micro element electrode to apply test voltage on the test circuit to form a test hoop for testing the micro element and obtaining defect pattern of the micro element of the carrier substrate.","S240 includes using the pick-up head array to pick up acceptable micro elements from the carrier substrate S250 includes releasing the micro elements to the receiving substrate Referring to FIG.","21, provide a transfer device 1100, and position it on the micro element 1200 which is connected to the carrier substrate 1300.Brief description is given below taking the transfer device 1100 of the first preferred embodiment of the present invention as an example.","Place the micro element on the carrier substrate 1300, with electrodes upwards, and the test electrodes 1134A and 1134B of the transfer device 1100 align with the micro element electrodes 1120A and 1120B respectively.","For simplification, the figure only shows four micro elements 1201-1204.Referring to FIG.","22, contact the pick-up head 1120 of the transfer device with the micro element.","The test electrode is connected to the micro element electrode, and applies voltage on both ends of the test electrode to form a test loop for testing the micro element and obtaining defect patterns of the micro element.","For example, photoelectric parameters of the micro element 1204 are qualified, and photoelectric parameters of the micro element 1201-1203 are not qualified.","Referring to FIG.","23, by controlling the pick-up head array of the transfer device, selectively pick up qualified micro elements 1201-1203 on the carrier substrate 1300.In this embodiment, the micro element array has 10 μm interval, wherein, each micro element has 2 μm interval and 8 μm maximum width.","Top surface of each micro element has a width approximating to 8 μm, and width of the surface of the corresponding pick-up head for contacting with the micro element is near 8 μm or less, thus avoiding unintentional contact with adjacent micro LED device.","The embodiments of the present invention can be any appropriate sizes, and not limited to such sizes.","Referring to FIG.","24, release the micro elements 1201-1203 on the acceptor substrate 1400.The acceptor substrate can be automotive glass, glass sheet, flexible electronic substrate, such as flexible film of path, display back plate, solar glass, metal, polymer, polymer compound and glass fiber.","In this embodiment, when the transfer device contacts with the micro element array, the test circuit of the transfer device tests the micro element to obtain defect pattern of the micro element array.","Then, selectively pick up qualified micro elements to effectively prevent defect micro elements from transfer-printing to the acceptor substrate of terminal applications such as the display backboard during transformation.","FIG.","25 is a flow diagram of a transfer method of the micro element according to the seventh preferred embodiment of the present invention, mainly comprises steps S310-S350, wherein, steps S310-S330 are same as steps S210-S230.Brief description is given below targeting at steps S340-S350.Referring to FIG.","26, by controlling the pick-up head array of the transfer device, selectively pick up unqualified micro elements 1204 on the carrier substrate 1300; referring to FIG.","27, release unqualified micro elements 1204 on the acceptor substrate 1500.In this embodiment, the acceptor substrate 1500 can be any recovery device for recovering and placing the unqualified micro element.","In this embodiment, before transfer of the micro element, at first, test the micro element array with the test circuit of the transfer device, and transfer it to the recovery device.","Therefore, those remained on the micro element of the carrier substrate are qualified products for prior removal of unqualified micro elements.","FIG.","28 is a flow diagram of a transfer method of the micro element according to the eighth preferred embodiment of the present invention, mainly comprises steps S410-S450, wherein, steps S410-S430 are basically same as steps S210-S230.Brief description is given below targeting at steps S440-S450.Referring to FIG.","29, by controlling the pick-up head array of the transfer device, selectively pick up the micro elements 1201-1204 on the carrier substrate 1300; referring to FIG.","30, by controlling, selectively release unqualified micro elements 1204 on the first acceptor substrate 1500; referring to FIG.","31, release qualified micro elements 1201-1203 on the second acceptor substrate 1400.In this embodiment, the first acceptor substrate 1500 can be any recovery device for recovering and placing the unqualified micro element; the second acceptor substrate 1400 can be a flexible electronic substrate, such as a flexible film with a circuit, display back plate, and the like.","In S450 of this embodiment, it is acceptable to release qualified micro elements 1201-1203 on the second acceptor substrate 1400 and then release unqualified micro elements 1204 on the first acceptor substrate 1500.FIG.","32 is a flow diagram of a transfer method of the micro element according to the ninth preferred embodiment of the present invention, mainly comprising steps S510-S570, wherein, steps S510-S520 are basically same as S210-S220.Brief description is given below targeting at steps S530-S570.Referring to FIG.","33, use the pick-up head array of the transfer device to selectively pick up the micro elements 1201-1204 on the carrier substrate 1300; referring to FIG.","34, release the micro elements 1201-1204 on the second acceptor substrate 1400.The pick-up head of the transfer device keeps contact with the micro element, and the test electrode of the transfer device contacts with the micro element electrode; referring to FIG.","35, apply voltage on the test electrode, and each micro element 1201-1204 forms a sub-test hoop for testing and obtaining the defect pattern of the micro element.","For example, photoelectric parameters of the micro element 1201 are unqualified (namely, the defect micro element), and photoelectric parameters of the micro element 1202-1204 are qualified; referring to FIG.","36, use the pick-up head array of the transfer device to selectively pick up the defect micro element 1201 of the second acceptor substrate 1400; referring to FIG.","37, release the defect micro element 1201 on the first acceptor substrate 1500, wherein, the first acceptor substrate 1500 can be any recovery device for recovering and placing the unqualified micro element; and the second acceptor substrate 1400 is a flexible electronic substrate, such as a flexible film with a circuit, display back plate, and the like.","The pick-up head arrays according to the above embodiments pick up or release micro elements through electrostatic force, Van der Waals force and vacuum adsorption force.","The transfer method of the micro element of each embodiment takes the transfer device 1100 disclosed in FIG.","1 as an example.","However, this invention is not limited to this transfer device.","For micro elements with different electrode structures, the transfer devices of different structures can be selected.","In the transfer method of the micro element, the micro element arrays can be tested and transfer printed for several times through the transfer device.","The transfer method for the micro element according to aforesaid embodiment can also be used for fabricating electronic device, or be widely applied in electronic devices like mobile phone, tablet PC, and the like.","Despite the description of exemplary embodiments of the present invention, it should be understood that it is not intended to limit the scope of the invention to the particular form set forth.","On the contrary, alternatives and modifications can be made by the persons skilled in the art without departing from the spirit and scope of the invention as defined by the appended claims."]],"string":"[\n [\n \"Micro Elements Transfer Device and Method\",\n \"A transfer device for micro element with a test circuit can test the micro element during transfer.\",\n \"The transfer device for micro elements includes: a base substrate, having two surfaces opposite to each other; a pick-up head array, formed over the first surface of the base substrate for picking up or releasing the micro element; a test circuit set inside or/on the surface of the base substrate, which has a series of sub-test circuits, each sub-test circuit at least having two test electrodes for simultaneous test of photoelectric parameters of the micro element when the transfer device transfers the micro element.\"\n ],\n [\n \"1.A transfer device of micro element comprising: a base substrate, having two surfaces opposite to each other; a pick-up head array, formed over the first surface of the base substrate for picking up or releasing the micro element; and a test circuit set inside or/on the surface of the base substrate, which has a series of sub-test circuits, each sub-test circuit at least having two test electrodes for simultaneous test of photoelectric parameters of the micro element when the transfer device transfers the micro element.\",\n \"2.The transfer device of claim 1, wherein: at least one test electrode of each sub-test circuit is formed over the surface of the pick-up head for contacting with the micro element, and connects to the micro element electrode when the pick-up head array contacts with the micro element.\",\n \"3.The transfer device of claim 2, wherein: each sub-test circuit has a pair of test electrodes respectively.\",\n \"4.The transfer device of claim 2, wherein: each sub-test circuit shares a test electrode.\",\n \"5.The transfer device of claim 2, wherein: the test circuit also comprises a retractable electrode located on the first surface of the base substrate, which forms a sub-test circuit together with the test electrode formed over the surface of the pick-up head for contacting with the micro element.\",\n \"6.The transfer device of claim 1, wherein: the transfer device also comprises a CMOS integrated circuit over the second surface of the base substrate, which connects to the test circuit.\",\n \"7.The transfer device of claim 6, wherein: the base substrate has a through-hole structure, wherein, the test circuit passes through the through-hole structure and extends to the second surface of the base substrate.\",\n \"8.The transfer device of claim 6, wherein: the base substrate is a Si substrate, and the CMOS integrated circuit is formed by a portion of the Si substrate.\",\n \"9.The transfer device of claim 6, wherein: the CMOS integrated circuit is a structure layer formed over the base substrate.\",\n \"10.The transfer device of claim 1, wherein: the pick-up head array picks up the micro element through electrostatic force, Van der Waals force and vacuum adsorption force.\",\n \"11.The transfer device of claim 1, wherein: the pick-up head has a static electrode layer and a dielectric layer cladding on the electrode layer, wherein, when the electrode layer applies absorption voltage, the pick-up head produces static attraction force to pick up the micro element contact therewith.\",\n \"12.The transfer device of claim 1, wherein: the surface of each pick-up head of the pick-up head array is made of biomimetic gecko material to absorb the micro element by virtue of absorption capacity of the biomimetic gecko material.\",\n \"13.The transfer device of claim 1, wherein: the pick-up head array is a series of suction nozzle arrays, which absorb or release the micro element through vacuum pressure.\",\n \"14.The transfer device of claim 13, wherein: the transfer device also comprises a cavity, a plurality of vacuum paths and a switch component, wherein, the suction nozzle array is connected to the cavity via a plurality of the vacuum paths, and valves are set at the connection place for switching on/off, and the switch component is used for controlling on or off of the valve of each vacuum path so that the suction nozzle is controlled to absorb or release required micro element through vacuum pressure.\",\n \"15.The transfer device of claim 14, wherein: the switch component comprises a CMOS integrated circuit and an address electrode array connected to the CMOS integrated circuit, wherein, each vacuum path valve corresponds to the address electrode array.\",\n \"16.The transfer device of claim 15, wherein: the valve is a movable member, wherein, the address electrode array is under selective excitation by the CMOS integrated circuit with voltage potential to generate electrostatic attraction, through which, corresponding movable member would deflect or approach to corresponding address electrode, thus controlling opening or closing of each vacuum path.\",\n \"17.The transfer device of claim 14, wherein: the vacuum path is a series of micro-hole structures passing through the base substrate, wherein, one end is connected to the cavity, and the other is connected to the suction nozzle.\",\n \"18.A transfer method of a micro element, the method comprising: (1) providing a transfer device, which comprises a base substrate, a pick-up head array formed over the surface of the base substrate and a test circuit inside or/and on the surface of the base substrate, wherein, the test circuit has a series of sub-test circuits, each sub-test circuit having at least two test electrodes; (2) positioning the transfer device on the micro element connected to the carrier substrate; and (3) contacting the test electrode of the transfer device with the micro element electrode to apply test voltage on the test circuit to form a test hoop for testing the micro element and obtaining defect pattern of the micro element of the carrier substrate.\",\n \"19.The transfer method of claim 18, further comprising: (4) using the pick-up array of the transfer device to pick up qualified micro elements on the carrier substrate; (5) releasing micro elements on the acceptor substrate.\",\n \"20.The transfer method of claim 18, further comprising: (4) using the pick-up array of the transfer device to pick up unqualified micro elements on the carrier substrate; (5) releasing unqualified micro elements on the acceptor substrate.\"\n ],\n [\n \" BACKGROUND Micro element technologies refer to integrate micro-size element arrays in high density over the substrate.\",\n \"At present, the micro light emitting diode (Micro LED) technique is becoming a hot research topic, and the industry circle expects high-quality micro element products in the market.\",\n \"High-quality micro light emitting diode products have profound impacts on conventional display products in the market, such as LCD/OLED.\",\n \"During fabrication of the micro element, at first, a micro element is formed over the donor substrate, and then the micro element is transferred to the acceptor substrate.\",\n \"For example, the acceptor substrate is a display screen.\"\n ],\n [\n \" SUMMARY The inventors of the present disclosure have recognized that, one difficulty during micro element fabrication is: how to transfer the micro element from the donor substrate to the acceptor substrate.\",\n \"In conventional micro element transfer, the micro element is transferred to the acceptor substrate through a transfer substrate via wafer bonding.\",\n \"Direct transfer is a kind of method by directly bonding the micro element array to the acceptor substrate from the transfer substrate, and then removing the transfer substrate.\",\n \"Indirect transfer is the other method.\",\n \"This method includes two times of bonding/lifting-off steps.\",\n \"At first, the transfer substrate extracts the micro element array from the donor substrate, and bonds the micro element array to the acceptor substrate.\",\n \"Finally, remove the transfer substrate.\",\n \"The micro element array is generally extracted by electrostatic method.\",\n \"During electrostatic extraction, a transfer head array is required.\",\n \"Embodiments of the present disclosure provide a transfer device of micro element with a test circuit, to test micro elements and remove unqualified micro elements during transfer.\",\n \"In an aspect: a transfer device of micro element is provided, including: a base substrate, having two surfaces opposite to each other; a pick-up head array, formed over the first surface of the base substrate for picking up or releasing the micro element; a test circuit set inside or/on the surface of the base substrate, which has a series of sub-test circuits, each sub-test circuit at least having two test electrodes for simultaneous test of photoelectric parameters of the micro element when the transfer device transfers the micro element.\",\n \"In some embodiments, at least one test electrode of each sub-test circuit is formed over the surface of the pick-up head for contacting with the micro element, and for connecting the micro element electrode when the pick-up head array contacts with the micro element.\",\n \"In some embodiments, the test circuit also comprises a retractable electrode located on the first surface of the base substrate, which forms a sub-test circuit together with the test electrode formed over the surface of the pick-up head for contacting with the micro element, which can be applied in micro elements with electrodes at different sides, such as a vertical micro light emitting diode.\",\n \"In some embodiments, the transfer device also comprises a CMOS integrated circuit over the second surface of the base substrate, which connects to the test circuit.\",\n \"In some embodiments, the base substrate has a through-hole structure, wherein, the test circuit passes through the through-hole structure and extends to the second surface of the base substrate.\",\n \"In some embodiments, the base substrate is a Si substrate, and the CMOS integrated circuit is formed by a portion of the Si substrate.\",\n \"In some embodiments, the CMOS integrated circuit is a structure layer formed over the base substrate.\",\n \"In some embodiments, the pick-up head array picks up the micro element through electrostatic force, Van der Waals force and vacuum adsorption force.\",\n \"In some embodiments, the pick-up head has a static electrode layer and a dielectric layer on the electrode layer, wherein, when the electrode layer applies absorption voltage, the pick-up head produces static attraction force to pick up the micro element contact therewith.\",\n \"In some embodiments, the surface of each pick-up head of the pick-up head array is made of biomimetic gecko material to absorb the micro element by virtue of absorption capacity of the biomimetic gecko material.\",\n \"In some embodiments, the pick-up head array is a series of suction nozzle arrays, which absorb or release the micro element through vacuum pressure.\",\n \"In an embodiment, the transfer device also comprises a cavity, a plurality of vacuum paths and a switch component, wherein, the suction nozzle array is connected to the cavity via a plurality of vacuum paths, and valves are set at the connection place for switching on/off.\",\n \"The switch component is used for controlling on or off of the valve of each vacuum path so that the suction nozzle is controlled to absorb or release required micro element through vacuum pressure.\",\n \"In some embodiments, the switch component comprises a CMOS integrated circuit and an address electrode array connected to the CMOS integrated circuit, wherein, each vacuum path valve corresponds to the address electrode array.\",\n \"In some embodiments, the valve is a movable member, wherein, the address electrode array is under selective excitation by the CMOS integrated circuit with voltage potential to generate electrostatic attraction, through which, corresponding movable member would deflect or approach to corresponding address electrode, thus controlling opening or closing of each vacuum path.\",\n \"In some embodiments, the vacuum path is a series of micro-hole structures passing through the base substrate, wherein, one end is connected to the cavity, and the other is connected to the suction nozzle.\",\n \"In some embodiments, the pick-up head size is below 100 μm, and the space is below 200 μm.\",\n \"Various embodiments of the present disclosure also provide a transfer method for prior removal of micro element defects, comprising: providing a transfer device, which comprises a base substrate, a pick-up head array formed over the surface of the base substrate and a test circuit inside or/and on the surface of the base substrate, wherein, the test circuit has a series of sub-test circuits, each sub-test circuit having at least two test electrodes; positioning the transfer device on the micro element connected to the carrier substrate so that the test electrode contacts with the micro element; applying test voltage on the test circuit to form a test hoop for testing the micro element and obtaining defect pattern of the micro element of the carrier substrate.\",\n \"In some embodiments, a transfer method for prior removal of micro element defects is disclosed, comprising: (1) providing a transfer device, which comprises a base substrate, a pick-up head array formed over the surface of the base substrate and a test circuit inside or/and on the surface of the base substrate, wherein, the test circuit has a series of sub-test circuits, each sub-test circuit having at least two test electrodes; (2) positioning the transfer device on the micro element connected to the carrier substrate; (3) contacting the test electrode with the micro element electrode, and applying test voltage on the test circuit to form a test hoop for testing the micro element and obtaining defect pattern of the micro element of the carrier substrate; (4) picking up qualified micro elements over the carrier substrate with the pick-up head array of the transfer device; and (5) releasing required micro elements on the acceptor substrate.\",\n \"In some embodiments, a transfer method for prior removal of micro element defects is disclosed, comprising: (1) providing a transfer device, which comprises a base substrate, a pick-up head array formed over the surface of the base substrate and a test circuit inside or/and on the surface of the base substrate, wherein, the test circuit has a series of sub-test circuits, each sub-test circuit having at least two test electrodes; (2) positioning the transfer device on the micro element connected to the carrier substrate; (3) contacting the test electrode with the micro element electrode, and applying test voltage on the test circuit to form a test hoop for testing the micro element and obtaining defect pattern of the micro element of the carrier substrate; (4) picking up unqualified micro elements over the carrier substrate with the pick-up head array of the transfer device; and (5) releasing unqualified micro elements on the acceptor substrate.\",\n \"In some embodiments, a transfer method for prior removal of micro element defects is disclosed, comprising: (1) providing a transfer device, which comprises a base substrate, a pick-up head array formed over the surface of the base substrate and a test circuit inside or/and on the surface of the base substrate, wherein, the test circuit has a series of sub-test circuits, each sub-test circuit having at least two test electrodes; (2) positioning the transfer device on the micro element connected to the carrier substrate; (3) contacting the test electrode with the micro element electrode, and applying test voltage on the test circuit to form a test hoop for testing the micro element and obtaining defect pattern of the micro element of the carrier substrate; (4) picking up micro elements over the carrier substrate with the pick-up head array of the transfer device; and (5) releasing unqualified and qualified micro elements onto different acceptor substrates respectively.\",\n \"In some embodiments, a transfer method for prior removal of micro element defects is disclosed, comprising: (1) providing a transfer device, which comprises a base substrate, a pick-up head array formed over the surface of the base substrate and a test circuit inside or/and on the surface of the base substrate, wherein, the test circuit has a series of sub-test circuits, each sub-test circuit having at least two test electrodes; (2) positioning the transfer device on the micro element connected to the carrier substrate; (3) picking up the micro elements of the carrier substrate with the pick-up head array of the transfer device; (4) releasing the micro elements on the first acceptor substrate; (5) contacting the test electrode of the transfer device with the micro element electrode, and applying test voltage on the test circuit to form a test hoop for testing the micro element and obtaining defect pattern of the micro element of the first acceptor substrate; (6) picking up unqualified micro elements on the first acceptor substrate with the pick-up head array of the transfer device; and (7) releasing unqualified micro elements on the second acceptor substrate.\",\n \"In some embodiments, the pick-up head array can pick up the micro element through electrostatic force, Van der Waals force and vacuum adsorption force.\",\n \"According to another embodiment of the present invention, a method for fabricating a micro element device is provided, comprising the transfer of the micro element to the receiving substrate of the micro element device through the method disclosed in the present invention.\",\n \"According to another embodiment of the present invention, a micro element device fabricated according to the method disclosed in the present invention is provided.\",\n \"According to another embodiment of the present invention, an electronic device comprising the micro element device of the present invention is provided.\",\n \"In some embodiments, the method above can further include: (4) using the pick-up array of the transfer device to pick up micro elements on the carrier substrate; (5) releasing unqualified and qualified micro elements on different acceptor substrates.\",\n \"In another aspect, a transfer method of micro element is provided, the method including: (1) providing a transfer device, which comprises a base substrate, a pick-up head array formed over the surface of the base substrate and a test circuit inside or/and on the surface of the base substrate, wherein, the test circuit has a series of sub-test circuits, each sub-test circuit having at least two test electrodes; (2) positioning the transfer device on the micro element connected to the carrier substrate; (3) using the pick-up array of the transfer device to pick up micro elements on the carrier substrate; (4) releasing micro elements on the first acceptor substrate; (5) contacting the test electrode of the transfer device with the micro element electrode to apply test voltage on the test circuit to form a test loop for testing the micro element and obtaining defect pattern of the micro element of the first acceptor substrate; (6) using the pick-up array of the transfer device to pick up unqualified micro elements on the first acceptor substrate; (7) releasing unqualified micro elements on the second acceptor substrate.\",\n \"In another aspect, a method for fabricating a micro element device, is provided, including any of micro element transfer method with prior removal of defects as described above.\",\n \"In another aspect, a micro element device fabricated according to the method above is provided.\",\n \"In another aspect, an electronic device including the micro element device described above is provided.\",\n \"The other features and advantages of this present disclosure will be described in detail in the following specification, and it is believed that such features and advantages will become more obvious in the specification or through implementations of this invention.\",\n \"The purposes and other advantages of the present disclosure can be realized and obtained in the structures specifically described in the specifications, claims and drawings.\",\n \"In addition, it should be understood by those skilled in the art that despite many problems in the prior art, the technical scheme of each embodiment or claim of the present invention can be improved in one or several aspects.\",\n \"It is not necessary to solve all technical problems listed in the prior art or the background art.\",\n \"It should be understood by those skilled in the art that contents not mentioned in a claim shall not be construed as limiting the claim.\"\n ],\n [\n \"CROSS-REFERENCE TO RELATED APPLICATIONS The present application is a continuation of, and claims priority to, PCT/CN2016/104869 filed on Nov. 7, 2016, which claims priority to Chinese Patent Application No.\",\n \"201610961364.5 filed on Nov. 4, 2016.The disclosures of these applications are hereby incorporated by reference in their entirety.\",\n \"BACKGROUND Micro element technologies refer to integrate micro-size element arrays in high density over the substrate.\",\n \"At present, the micro light emitting diode (Micro LED) technique is becoming a hot research topic, and the industry circle expects high-quality micro element products in the market.\",\n \"High-quality micro light emitting diode products have profound impacts on conventional display products in the market, such as LCD/OLED.\",\n \"During fabrication of the micro element, at first, a micro element is formed over the donor substrate, and then the micro element is transferred to the acceptor substrate.\",\n \"For example, the acceptor substrate is a display screen.\",\n \"SUMMARY The inventors of the present disclosure have recognized that, one difficulty during micro element fabrication is: how to transfer the micro element from the donor substrate to the acceptor substrate.\",\n \"In conventional micro element transfer, the micro element is transferred to the acceptor substrate through a transfer substrate via wafer bonding.\",\n \"Direct transfer is a kind of method by directly bonding the micro element array to the acceptor substrate from the transfer substrate, and then removing the transfer substrate.\",\n \"Indirect transfer is the other method.\",\n \"This method includes two times of bonding/lifting-off steps.\",\n \"At first, the transfer substrate extracts the micro element array from the donor substrate, and bonds the micro element array to the acceptor substrate.\",\n \"Finally, remove the transfer substrate.\",\n \"The micro element array is generally extracted by electrostatic method.\",\n \"During electrostatic extraction, a transfer head array is required.\",\n \"Embodiments of the present disclosure provide a transfer device of micro element with a test circuit, to test micro elements and remove unqualified micro elements during transfer.\",\n \"In an aspect: a transfer device of micro element is provided, including: a base substrate, having two surfaces opposite to each other; a pick-up head array, formed over the first surface of the base substrate for picking up or releasing the micro element; a test circuit set inside or/on the surface of the base substrate, which has a series of sub-test circuits, each sub-test circuit at least having two test electrodes for simultaneous test of photoelectric parameters of the micro element when the transfer device transfers the micro element.\",\n \"In some embodiments, at least one test electrode of each sub-test circuit is formed over the surface of the pick-up head for contacting with the micro element, and for connecting the micro element electrode when the pick-up head array contacts with the micro element.\",\n \"In some embodiments, the test circuit also comprises a retractable electrode located on the first surface of the base substrate, which forms a sub-test circuit together with the test electrode formed over the surface of the pick-up head for contacting with the micro element, which can be applied in micro elements with electrodes at different sides, such as a vertical micro light emitting diode.\",\n \"In some embodiments, the transfer device also comprises a CMOS integrated circuit over the second surface of the base substrate, which connects to the test circuit.\",\n \"In some embodiments, the base substrate has a through-hole structure, wherein, the test circuit passes through the through-hole structure and extends to the second surface of the base substrate.\",\n \"In some embodiments, the base substrate is a Si substrate, and the CMOS integrated circuit is formed by a portion of the Si substrate.\",\n \"In some embodiments, the CMOS integrated circuit is a structure layer formed over the base substrate.\",\n \"In some embodiments, the pick-up head array picks up the micro element through electrostatic force, Van der Waals force and vacuum adsorption force.\",\n \"In some embodiments, the pick-up head has a static electrode layer and a dielectric layer on the electrode layer, wherein, when the electrode layer applies absorption voltage, the pick-up head produces static attraction force to pick up the micro element contact therewith.\",\n \"In some embodiments, the surface of each pick-up head of the pick-up head array is made of biomimetic gecko material to absorb the micro element by virtue of absorption capacity of the biomimetic gecko material.\",\n \"In some embodiments, the pick-up head array is a series of suction nozzle arrays, which absorb or release the micro element through vacuum pressure.\",\n \"In an embodiment, the transfer device also comprises a cavity, a plurality of vacuum paths and a switch component, wherein, the suction nozzle array is connected to the cavity via a plurality of vacuum paths, and valves are set at the connection place for switching on/off.\",\n \"The switch component is used for controlling on or off of the valve of each vacuum path so that the suction nozzle is controlled to absorb or release required micro element through vacuum pressure.\",\n \"In some embodiments, the switch component comprises a CMOS integrated circuit and an address electrode array connected to the CMOS integrated circuit, wherein, each vacuum path valve corresponds to the address electrode array.\",\n \"In some embodiments, the valve is a movable member, wherein, the address electrode array is under selective excitation by the CMOS integrated circuit with voltage potential to generate electrostatic attraction, through which, corresponding movable member would deflect or approach to corresponding address electrode, thus controlling opening or closing of each vacuum path.\",\n \"In some embodiments, the vacuum path is a series of micro-hole structures passing through the base substrate, wherein, one end is connected to the cavity, and the other is connected to the suction nozzle.\",\n \"In some embodiments, the pick-up head size is below 100 μm, and the space is below 200 μm.\",\n \"Various embodiments of the present disclosure also provide a transfer method for prior removal of micro element defects, comprising: providing a transfer device, which comprises a base substrate, a pick-up head array formed over the surface of the base substrate and a test circuit inside or/and on the surface of the base substrate, wherein, the test circuit has a series of sub-test circuits, each sub-test circuit having at least two test electrodes; positioning the transfer device on the micro element connected to the carrier substrate so that the test electrode contacts with the micro element; applying test voltage on the test circuit to form a test hoop for testing the micro element and obtaining defect pattern of the micro element of the carrier substrate.\",\n \"In some embodiments, a transfer method for prior removal of micro element defects is disclosed, comprising: (1) providing a transfer device, which comprises a base substrate, a pick-up head array formed over the surface of the base substrate and a test circuit inside or/and on the surface of the base substrate, wherein, the test circuit has a series of sub-test circuits, each sub-test circuit having at least two test electrodes; (2) positioning the transfer device on the micro element connected to the carrier substrate; (3) contacting the test electrode with the micro element electrode, and applying test voltage on the test circuit to form a test hoop for testing the micro element and obtaining defect pattern of the micro element of the carrier substrate; (4) picking up qualified micro elements over the carrier substrate with the pick-up head array of the transfer device; and (5) releasing required micro elements on the acceptor substrate.\",\n \"In some embodiments, a transfer method for prior removal of micro element defects is disclosed, comprising: (1) providing a transfer device, which comprises a base substrate, a pick-up head array formed over the surface of the base substrate and a test circuit inside or/and on the surface of the base substrate, wherein, the test circuit has a series of sub-test circuits, each sub-test circuit having at least two test electrodes; (2) positioning the transfer device on the micro element connected to the carrier substrate; (3) contacting the test electrode with the micro element electrode, and applying test voltage on the test circuit to form a test hoop for testing the micro element and obtaining defect pattern of the micro element of the carrier substrate; (4) picking up unqualified micro elements over the carrier substrate with the pick-up head array of the transfer device; and (5) releasing unqualified micro elements on the acceptor substrate.\",\n \"In some embodiments, a transfer method for prior removal of micro element defects is disclosed, comprising: (1) providing a transfer device, which comprises a base substrate, a pick-up head array formed over the surface of the base substrate and a test circuit inside or/and on the surface of the base substrate, wherein, the test circuit has a series of sub-test circuits, each sub-test circuit having at least two test electrodes; (2) positioning the transfer device on the micro element connected to the carrier substrate; (3) contacting the test electrode with the micro element electrode, and applying test voltage on the test circuit to form a test hoop for testing the micro element and obtaining defect pattern of the micro element of the carrier substrate; (4) picking up micro elements over the carrier substrate with the pick-up head array of the transfer device; and (5) releasing unqualified and qualified micro elements onto different acceptor substrates respectively.\",\n \"In some embodiments, a transfer method for prior removal of micro element defects is disclosed, comprising: (1) providing a transfer device, which comprises a base substrate, a pick-up head array formed over the surface of the base substrate and a test circuit inside or/and on the surface of the base substrate, wherein, the test circuit has a series of sub-test circuits, each sub-test circuit having at least two test electrodes; (2) positioning the transfer device on the micro element connected to the carrier substrate; (3) picking up the micro elements of the carrier substrate with the pick-up head array of the transfer device; (4) releasing the micro elements on the first acceptor substrate; (5) contacting the test electrode of the transfer device with the micro element electrode, and applying test voltage on the test circuit to form a test hoop for testing the micro element and obtaining defect pattern of the micro element of the first acceptor substrate; (6) picking up unqualified micro elements on the first acceptor substrate with the pick-up head array of the transfer device; and (7) releasing unqualified micro elements on the second acceptor substrate.\",\n \"In some embodiments, the pick-up head array can pick up the micro element through electrostatic force, Van der Waals force and vacuum adsorption force.\",\n \"According to another embodiment of the present invention, a method for fabricating a micro element device is provided, comprising the transfer of the micro element to the receiving substrate of the micro element device through the method disclosed in the present invention.\",\n \"According to another embodiment of the present invention, a micro element device fabricated according to the method disclosed in the present invention is provided.\",\n \"According to another embodiment of the present invention, an electronic device comprising the micro element device of the present invention is provided.\",\n \"In some embodiments, the method above can further include: (4) using the pick-up array of the transfer device to pick up micro elements on the carrier substrate; (5) releasing unqualified and qualified micro elements on different acceptor substrates.\",\n \"In another aspect, a transfer method of micro element is provided, the method including: (1) providing a transfer device, which comprises a base substrate, a pick-up head array formed over the surface of the base substrate and a test circuit inside or/and on the surface of the base substrate, wherein, the test circuit has a series of sub-test circuits, each sub-test circuit having at least two test electrodes; (2) positioning the transfer device on the micro element connected to the carrier substrate; (3) using the pick-up array of the transfer device to pick up micro elements on the carrier substrate; (4) releasing micro elements on the first acceptor substrate; (5) contacting the test electrode of the transfer device with the micro element electrode to apply test voltage on the test circuit to form a test loop for testing the micro element and obtaining defect pattern of the micro element of the first acceptor substrate; (6) using the pick-up array of the transfer device to pick up unqualified micro elements on the first acceptor substrate; (7) releasing unqualified micro elements on the second acceptor substrate.\",\n \"In another aspect, a method for fabricating a micro element device, is provided, including any of micro element transfer method with prior removal of defects as described above.\",\n \"In another aspect, a micro element device fabricated according to the method above is provided.\",\n \"In another aspect, an electronic device including the micro element device described above is provided.\",\n \"The other features and advantages of this present disclosure will be described in detail in the following specification, and it is believed that such features and advantages will become more obvious in the specification or through implementations of this invention.\",\n \"The purposes and other advantages of the present disclosure can be realized and obtained in the structures specifically described in the specifications, claims and drawings.\",\n \"In addition, it should be understood by those skilled in the art that despite many problems in the prior art, the technical scheme of each embodiment or claim of the present invention can be improved in one or several aspects.\",\n \"It is not necessary to solve all technical problems listed in the prior art or the background art.\",\n \"It should be understood by those skilled in the art that contents not mentioned in a claim shall not be construed as limiting the claim.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings, which are included to provide a further understanding of the invention and constitute a part of this specification, together with the embodiments, are therefore to be considered in all respects as illustrative and not restrictive.\",\n \"In addition, the drawings are merely illustrative, which are not drawn to scale.\",\n \"FIG.\",\n \"1 is a side sectional view of a transfer device of micro element according to a first embodiment of the present disclosure.\",\n \"FIG.\",\n \"2 is a schematic diagram showing that voltage is applied on the electrode layer of the pick-up head of the transfer device as shown in FIG.\",\n \"1 to produce statistic absorption force.\",\n \"FIG.\",\n \"3 is a schematic diagram showing that voltage is applied on the test circuit of the transfer device as shown in FIG.\",\n \"1 to form a test hoop.\",\n \"FIG.\",\n \"4 is a side sectional view of a transfer device of micro element according to a second embodiment of the present disclosure.\",\n \"FIG.\",\n \"5 is a schematic diagram showing that voltage is applied on the test circuit of the transfer device as shown in FIG.\",\n \"4 to test the micro element.\",\n \"FIG.\",\n \"6 is a schematic diagram showing that voltage is applied on the electrode layer of the pick-up head of the transfer device as shown in FIG.\",\n \"4 to produce statistic absorption force.\",\n \"FIG.\",\n \"7 is a side sectional view of a transfer device of micro element according to a third embodiment of the present disclosure.\",\n \"FIG.\",\n \"8 is a schematic diagram showing that voltage is applied on the test circuit of the transfer device as shown in FIG.\",\n \"7 to test the micro element.\",\n \"FIG.\",\n \"9 is a schematic diagram showing that voltage is applied on the electrode layer of the pick-up head of the transfer device as shown in FIG.\",\n \"7 to produce statistic absorption force.\",\n \"FIG.\",\n \"10 is a side sectional view of a transfer device of micro element according to a fourth preferred embodiment, wherein the surface of the pick-up head 4120 has a micro nanometer-composite rigid villi structure.\",\n \"FIG.\",\n \"11 is a SEM diagram of the rigid villi structure of the micro element transfer device as shown in FIG.\",\n \"10.FIG.\",\n \"12 is a side section view of a transfer device of micro element according to a fifth preferred embodiment.\",\n \"FIG.\",\n \"13 is a first schematic diagram illustrating the vacuum path valve of the micro element the transfer device.\",\n \"FIG.\",\n \"14 is a second schematic diagram illustrating the vacuum path valve of the micro element the transfer device.\",\n \"FIG.\",\n \"15 is a third schematic diagram illustrating the vacuum path valve of the micro element the transfer device.\",\n \"FIG.\",\n \"16 is a cross-section view of FIG.\",\n \"14 along line A-A.\",\n \"FIG.\",\n \"17 is a cross-sectional view of FIG.\",\n \"14 along line B-B, in which the vacuum path is OFF.\",\n \"FIG.\",\n \"18 is a cross-sectional view of FIG.\",\n \"14 along line B-B, in which the vacuum path is ON.\",\n \"FIG.\",\n \"19 is a flow chart illustrating prior removal of defects of a micro element during transfer according to the present invention.\",\n \"FIG.\",\n \"20 is a flow chart illustrating the transfer method of the micro element according to a sixth preferred embodiment.\",\n \"FIG.\",\n \"21 illustrates a first step of the transfer method of the micro element according to the sixth embodiment.\",\n \"FIG.\",\n \"22 illustrates a second step of the transfer method of the micro element according to the sixth embodiment.\",\n \"FIG.\",\n \"23 illustrates a third step of the transfer method of the micro element according to the sixth embodiment.\",\n \"FIG.\",\n \"24 illustrates a fourth step of the transfer method of the micro element according to the sixth embodiment.\",\n \"FIG.\",\n \"25 is flow chart illustrating the transfer method of the micro element according to a seventh embodiment.\",\n \"FIG.\",\n \"26 illustrates a first step of the transfer method of the micro element according to the seventh embodiment.\",\n \"FIG.\",\n \"27 illustrates a second step of the transfer method of the micro element according to the seventh embodiment.\",\n \"FIG.\",\n \"28 is flow chart illustrating the transfer method of the micro element according to an eighth embodiment.\",\n \"FIG.\",\n \"29 illustrates a first step of the transfer method of the micro element according to the eighth embodiment.\",\n \"FIG.\",\n \"30 illustrates a second step of the transfer method of the micro element according to the eighth embodiment.\",\n \"FIG.\",\n \"31 illustrates a third step of the transfer method of the micro element according to the eighth embodiment.\",\n \"FIG.\",\n \"32 is a flow chart illustrating the transfer method of the micro element according to a ninth embodiment.\",\n \"FIG.\",\n \"33 illustrates a first step of the transfer method of the micro element according to the ninth embodiment.\",\n \"FIG.\",\n \"34 illustrates a second step of the transfer method of the micro element according to the ninth embodiment.\",\n \"FIG.\",\n \"35 illustrates a third step of the transfer method of the micro element according to the ninth embodiment.\",\n \"FIG.\",\n \"36 illustrates a fourth step of the transfer method of the micro element according to the ninth embodiment.\",\n \"FIG.\",\n \"37 illustrates a fifth step of the transfer method of the micro element according to the ninth embodiment.\",\n \"In the drawings: 1100, 2100, 3100, 4100, 5100: transfer device; 1110, 2110, 3110, 4110, 5110: base substrate; 1110A: first surface of the base substrate; 1110B: second surface of the base substrate; 1120, 2120, 3120, 4120, 5120: pick-up head; 1120A: surface of the pick-up head for contacting with the micro element; 1122, 2122, 3122: electrostatic circuit connecting line of the pick-up head; 1124, 2124, 3124: electrode layer of the pick-up head; 1126, 2126, 3126: dielectric layer; 1132A, 1132B, 2132A, 2132B, 3132, 4132A, 4132B, 5132A, 5132B: circuit; 1134A, 1134B, 2134A, 2134B, 3134, 4134A, 4134B, 5134A, 5134B: test electrode; 2136, 3136: retractable electrode; 1140, 2140, 3140, 4140: CMOS integrated circuit; 1200, 2200, 3200: micro element; 1220A, 1220B, 3220: micro element electrode; 1300, 2300, 3300: carrier substrate; 1310, 2310, 3310: middle layer; 1140, 2140, 3140, 4140: CMOS integrated circuit; 5138: insulating protective layer; 5150: through hole/vacuum path; 5152: valve/movable member; 5154: carrier layer; 5160: cavity; 5170: CMOS integrated circuit; 5172: address electrode layer; 5174: address electrode.\",\n \"DETAILED DESCRIPTION This embodiment describes a micro element transfer device and method for transferring a micro element with the transfer device.\",\n \"The micro element array can be a micro LED device, a diode, a transistor, an integrated chip (IC), with size of 1-100 μm, which is not limited to this size.\",\n \"In addition, some aspects of the embodiment may apply to larger or smaller sizes.\",\n \"The embodiments below describe a micro element transfer device and method for transferring a micro element with the transfer device.\",\n \"The transfer device has a pick-up head array for picking up or releasing the micro element, and size (such as length or width) of each pick-up head is 1-100 μm.\",\n \"The transfer device also has a test circuit, and each pick-up head corresponds to a sub-test circuit.\",\n \"When the pick-up head contacts with the micro element, voltage is applied on the test circuit to form a test hoop for photoelectric performance test of the micro element.\",\n \"Therefore, defect pattern of the defect micro element is obtained to remove defect micro elements during micro element array transfer.\",\n \"FIG.\",\n \"1 is a side section view of a transfer device according to the first preferred embodiment of the present invention.\",\n \"The transfer device 1100 comprises: a base substrate 1110, an array of pick-up head 1120, a test circuit and a CMOS integrated circuit 1140.Specifically, the base substrate 1110 is for supporting, which can be made of a variety of materials, such as Si, ceramics and polymer.\",\n \"The pick-up head 1120 is formed over the first surface 1110A of the base substrate 1110 in an array arrangement.\",\n \"The size range is 1 μm-100 μm, and the size, for example, can be 50 μm-20 μm.\",\n \"The pitch is (1 μm-100 μm)×(1 μm-100 μm), such as 10 μm×10 μm or 50 μm×100 μm.\",\n \"The array of pick-up head 1120 is located on the first surface 1110A of the base substrate 1100 for picking up the micro element through various adsorption forces (such as electrostatic force, vacuum pressure, Van der Waals force, magnetic force and the like) for print transfer.\",\n \"In some embodiments, each pick-up head can be independently controllable for selective pick-up and release of the micro element.\",\n \"The test circuit is composed of a series of sub-test circuits, each sub-test circuit corresponding to a pick-up head 1120, and having at least two test electrodes 1134A and 1134B, wherein, the sub-test circuit is connected to the working electronic device of the test module such as CMOS integrated circuit 1140 via the circuits 1132A and 1132B.\",\n \"In this embodiment, the array of pick-up head 1120 picks up and releases the micro element through electrostatic force, wherein, each pick-up head 1120 corresponds to an electrostatic adsorption circuit, comprising a connection circuit 1122 and an electrode layer 1124, wherein, the connection line 1122 can go through the base substrate 1110, and connect to the CMOS integrated circuit 1140 so as to connect to external electronic control piece.\",\n \"The surface of the electrode layer 1124 is covered with a dielectric layer 1126.Thus, when absorption voltage is applied on the electrode layer 1124, electrostatic adsorption force is formed to pick up the micro element, as shown in FIG.\",\n \"2.The test circuit of the transfer device 1100 is composed of a series of sub-test circuits, and each pick-up head 1120 corresponds to a sub-test circuit, which is composed of test electrodes 1134A, 1134B and circuits 1132A, 1132B.\",\n \"A pair of through-hole structures are formed at a place of the base substrate 1110 approaching the pick-up head 1120, and the through holes are filled with conductive materials to form circuits 1132A and 1132B to connect the test electrodes 1134A, 1134B to the CMOS integrated circuit 1140 on the second surface 1100B of the base substrate.\",\n \"The test electrodes 1134A and 1134B are embedded in the dielectric layer 1126, and the lower surface is parallel with the lower surface of the dielectric layer 1126.At this time, the surface 1120A of the pick-up head 1120 for contacting with the micro element is composed of test electrodes 1134A, 1134B and the dielectric layer 1126, as shown in FIG.\",\n \"1.When the surface 1120A of the pick-up head 1120 contacts with the micro element, the test electrode 1134A contacts with the micro element electrode 1220A, and the test electrode 1134B contacts with the micro element electrode 1220B.\",\n \"The transfer device 1100 of this embodiment mainly targets at micro elements 1200 with electrodes at same side (for example, micro light emitting diode with electrodes at same side), and the test electrodes 1134A and 1134B are formed on the surface 1120A of the pick-up head 1120 for contacting with the micro element.\",\n \"Before transferring the micro element 1200 with the transfer device 1100, the micro element 1200 is generally placed on the carrier substrate 1300 (a middle layer 1310 can be set between them, but is not necessarily required), wherein, electrodes 1220A and 1220B are generally placed upwards.\",\n \"When the pick-up head 1120 of the transfer device 1100 aligns with the contact micro element 1200, the test electrode 1134A contacts with the micro element electrode 1220A, and the test electrode 1134B contacts with the micro element electrode 1220B.\",\n \"When test voltage is applied on test electrodes 1134A and 1134B through circuits 1132A and 1132B, a test hoop is formed, as shown in FIG.\",\n \"3 to realize photoelectric parameter test for the micro element.\",\n \"Thus, the micro elements are tested during transferring for prior removal of defect micro elements.\",\n \"FIG.\",\n \"4 is a side section view of a transfer device according to the second preferred embodiment of the present invention.\",\n \"Different from the transfer device 1100, the transfer device 2100 also has at least a retractable electrode 2136, which forms a sub-test circuit together with the test electrode 2134B formed over the surface of the pick-up head for contacting with the micro element, which can be applied for micro elements with electrodes at different sides, such as a vertical micro light emitting diode.\",\n \"The retractable electrode 2136 and the pick-up head 2120 are at the same side, which can be located outside the array of the pick-up head 2120, and the lower end 2136A extrudes the lower end 2120A of the pick-up head 2120.When the transfer device 2100 is used for transferring the vertical micro element, the vertical micro element 2200 is placed on the conductive carrier substrate 2300, and the pick-up head 2120 of the transfer device 2100 orients to and contacts with the micro element 2200, then the test electrode 2034B contacts with the top electrode 2220 of the micro element 2200, and the retractable electrode 2136 contacts with the carrier substrate 2300.FIGS.\",\n \"5 and 6 show circuit connections under the test mode and the pick-up mode.\",\n \"Referring to FIG.\",\n \"5, when the transfer device 2100 tests the micro element, test voltage connects the test electrode 2134B and the retractable electrode 2136, wherein, 2134B connects the top electrode 2220 of the micro element, and the retractable electrode 2136 connects the conductive substrate 2300 to form a test hoop to realize test for the micro element 2200; referring to FIG.\",\n \"6, when the transfer device 2100 picks up the micro element, when the absorption voltage connects the electrode layer 2124 of the electrostatic circuit, static attraction force is generated on the surface of the pick-up head 2120 to pick up the micro element contacted therewith.\",\n \"The transfer device of the embodiment can be used for testing and transfer printing of micro elements with electrodes at same or different sides (namely, the vertical micro element).\",\n \"When the transfer device is applied for transferring the vertical micro element, the test electrode 2134B and the retractable electrode 2136 form a test circuit; when the transfer device is applied for transferring horizontal micro elements, the test electrodes 2134B and 2134A form a test circuit.\",\n \"The retractable electrode 2136 can be used for electrostatic protection.\",\n \"FIG.\",\n \"7 is a side section view of a transfer device according to the third preferred embodiment of the present invention.\",\n \"Different from the transfer device 2100, the transfer device 3100 is mainly applied for vertical micro elements.\",\n \"In this embodiment, the test circuit is simplified as only one test electrode 3134 forms on the surface of the pick-up head 3120.FIGS.\",\n \"8 and 9 show circuit connections under the test mode and the pick-up mode.\",\n \"Referring to FIG.\",\n \"8, when the transfer device 3100 tests the micro element, the test voltage connects the test electrode 3134 and the retractable electrode 3136, wherein, the test electrode 3134 connects the top surface electrode 3220 of the micro element, and the retractable electrode 3136 connects to the conductive carrier substrate 3300 to form a test hoop for testing the micro element 3200; referring to FIG.\",\n \"9, when the transfer device 2100 picks up the micro element 3200, one end of the external power is directly grounded, and the other end connects to the electrode layer 3124.Static attraction force is produced on the surface of the pick-up head 3120 to pick up the micro element contact therewith.\",\n \"FIG.\",\n \"10 is a side section view of a transfer device according to the fourth preferred embodiment of the present invention.\",\n \"Different from the transfer device 1100, the pick-up head 4120 of the transfer device 4100 picks up and releases the micro element with Van der Waals force.\",\n \"In this embodiment, the surface of the pick-up head 4120 is made of biomimetic gecko.\",\n \"When it orients to and contacts with the micro element, the pick-up head absorbs the micro element by virtue of absorption capacity of the biomimetic gecko to pick up required micro element, and desorbs the micro element by virtue of desorption capacity the biomimetic gecko to release the micro element.\",\n \"In this embodiment, the test electrodes 4314A and 4134B are not necessarily to cover the surface of the pick-up head 4120, but to expose part of the test electrode on the surface of the pick-up head for contacting with the micro element to the extent that the test electrode can be connected to the micro element electrode when the pick-up head 4120 contacts the micro element.\",\n \"Specifically, the pick-up head 4120 is made of biomimetic gecko material, which can be silicone rubber, polyurethane, multiwalled carbon nanotube, polyester resin, polyimide, artificial rubber, epoxy resin, polydimethylsiloxane, polyurethane and ethylene glycol terephthalate or polymethyl methacrylate or any of their combinations.\",\n \"Further, the surface of the pick-up head 4120 comprises micro nanometer-composite rigid villi structure, as shown in FIG.\",\n \"11, for example, with protrusion density of 1×105-6×108 protrusions per cm2.Van der Waals force is produced when the rigid villi structure made of biomimetic gecko material contacts with the micro element surface with adhesive attraction, which absorbs the micro element to pick up the micro element.\",\n \"In some embodiments, the surface of the rigid villi structure has hydrophobic nature, which prevents water layer from being formed on the contact surface, which eliminates possible function of capillary force as much as possible, thus playing an important role for narrowing gap and providing Van der Waals force.\",\n \"FIG.\",\n \"12 is a side section view of a transfer device according to the fifth preferred embodiment of the present invention.\",\n \"Different from the transfer device 1100, the pick-up head 5120 of the transfer device 5100 is a suction nozzle structure, which picks up and releases the micro element through vacuum pressure adsorption.\",\n \"Specifically, the transfer device 5100 has a suction nozzle array.\",\n \"Each suction nozzle is connected to a same cavity 5160 through the vacuum path 5150, and each vacuum path has a valve 5152 to control ON/OFF of the vacuum path.\",\n \"Size (for example length or width) of each suction nozzle is 1-100 μm.\",\n \"Each suction nozzle is 1-20 μm.\",\n \"Pitch of the suction nozzle array is (1 μm-100 μm)×(1 μm-100 μm), for example 10 μm×10 μm or 50 μm×100 μm.\",\n \"To reach such size, each vacuum path can be a series of micro-hole structures formed over the base substrate 5110 (such as Si substrate).\",\n \"Correspondingly, each suction nozzle 5120 corresponds to a vacuum path 5150, a valve 5152 and a switch element.\",\n \"A CMOS storage circuit and an address electrode array can be used for providing the switch array with micro size.\",\n \"Digital micro-mirror device (DMD) is a single chip semiconductor device with micro electro mechanical system (MEMS), which generally comprises area arrays of bistable state movable micro-mirror for forming image elements (pixel).\",\n \"The micro-mirror is fabricated in the area array corresponding to the addressing memory unit and placed above related address electrode at the bottom of the micro-mirror, wherein, the address electrode is under selective excitation by the control circuit to generate electrostatic attraction causing corresponding micro-mirror to deflect towards corresponding address electrode.\",\n \"The embodiments, with the principle of DMD chip, a movable member of a micro-mirror similar to the DMD chip is set at the connection position of each vacuum path and the shared cavity, as a valve, and an associated address electrode is fabricated above the movable member, wherein, the address electrode is under selective excitation by the control circuit to generate electrostatic attraction causing corresponding movable member to deflect towards corresponding address electrode.\",\n \"In this way, the movable member skews or deflects to the address electrode to close or open the vacuum path, and controls each vacuum path valve via the switching component for controlling opening or closing of the vacuum path to extract required micro element.\",\n \"Referring to FIG.\",\n \"12, the transfer device 5100 comprises a base substrate 5110, a cavity 5160 above the base substrate 5110 and a switch array above the cavity 5160.Specifically, the base substrate 5110 has an array of through hole 5150, and a series of suction nozzle structures are formed at the bottom surface of the base substrate 5110 to serve as the pick-up head 5120.Conductive layers 5132A and 5132B are formed at the side wall of the through hole 5150, and extend towards the upper and lower surfaces of the base substrate 5110.Test electrode 5134A and 5134B are formed on the lower surface of the base substrate 5110.Cover a dielectric layer over the conductive layers 5132A and 5132B as the insulating protective layer 5138.The conductive layers 5132A, 5132B and the test electrodes 5134A, 5134B form a test circuit, wherein, a functional circuit (such as a CMOS integrated circuit, not shown) can be formed inside the base substrate 5110 for connecting the test circuit.\",\n \"In this embodiment, each suction nozzle 5120 is connected to a same cavity 5160 through the through hole 5150.As the vacuum path, each through hole 5150 is used for transmitting vacuum pressure so that the suction nozzle 5120 can absorb or release the micro element through vacuum pressure.\",\n \"Further, a valve 5152 is set at the opening of each through hole 5150 for controlling ON/OFF of each vacuum path 5150.The valve of each vacuum path is controlled by the switch component so as to control ON or OFF of the vacuum path to pick up required micro element.\",\n \"The switch array is composed of a CMOS storage circuit layer 5170 and an address electrode layer 5172 thereunder, wherein, the address electrode layer 5172 is provided with an array of address electrode 5174, each address electrode 5174 corresponding to a vacuum path 5150.In this embodiment, the valve 5152 is a member 5152 capable for deflection at the micro hole structure, wherein, the edge of this member is not connected to the through hole edge, but connects to the base substrate 5110 with a carrier layer 5154.Under electrostatic attraction of the address electrode 5174, the member 5152 deflects taking the pivot as the center, wherein, one end deflects towards the address electrode 5174.FIGS.\",\n \"13-15 are schematic diagrams of the vacuum path valve.\",\n \"The valve structure comprises a carrier layer 5154 on the surface of the base substrate 5110 and a movable member 5152 on the carrier layer 5154.The carrier layer 5154 comprises a frame 5154a, a pivot 5154b and an opening 5154c, wherein, the pivot 5154b is supported on the frame 5154a and cross the opening 5154c.\",\n \"The movable member 5152 is supported on the pivot 5154b through the hole 5152a, and can deflect or decline taking the pivot 5154b as the center.\",\n \"FIGS.\",\n \"16-18 are section views of each suction nozzle of the transfer device.\",\n \"FIG.\",\n \"16 is a schematic diagram along line A-A of FIG.\",\n \"14.As shown in the figure, in this embodiment, the upper surface of the pivot 5154b is lower than the frame 5154a, and the component 5152 suspends on the pivot 5154b.\",\n \"FIGS.\",\n \"17-18 are schematic diagrams along line A-A of FIG.\",\n \"12.As shown in the figure, an address electrode 5174 is arranged above the member 5152.The CMOS memory circuit controls the ON/OFF status of the address electrode 5174.When the address electrode 5174 is in OFF status, the address electrode 5174 is not excited with voltage potential so as not to generate electrostatic attraction, and the member 5152 is not deflected, thus closing the vacuum path 5150, as shown in FIG.\",\n \"17; when the address electrode 5174 is in ON status, the address electrode 5174 is excited with voltage potential to generate electrostatic attraction.\",\n \"Under electrostatic attraction of the address electrode 5174, the edge of the member 5152 deflects on the pivot 5154b and deflects towards the address electrode 5174, thus opening the vacuum path 5150, as shown in FIG.\",\n \"18.FIG.\",\n \"19 is a flow diagram of defect removal of the micro element through any of the aforesaid transfer device, which can include steps S110-S130.Brief description is given below.\",\n \"S110: provide any of the transfer devices.\",\n \"The transfer device comprises a pick-up head array and a test circuit, wherein, the test circuit is composed of a series of sub-test electrodes, and each sub-test circuit corresponds to a pick-up head.\",\n \"In some embodiments, in general, the device comprises two test electrodes, wherein, at least one test electrode is located over the surface of the pick-up head for contacting with the micro element, so that when the pick-up head contacts with the micro element, the test electrode injects test current to the micro element.\",\n \"S120: position the transfer device on the micro element connected to the carrier substrate.\",\n \"The carrier substrate can be a growth substrate or a carrier substrate; for example, the carrier substrate material can be glass, Si, polycarbonate (PC), acrylonitrile butadiene styrene (ABS) or any of their combination.\",\n \"The micro element can be a micro light emitting diode, with thickness of about 0.5 μm to about 100 μm.\",\n \"The micro element can be a cylinder with radius of about 0.5 μm to about 500 μm.\",\n \"However, the micro element is not limited to cylinder, but can be triangular column, cube, rectangular, hexagonal column, octagonal column or other polygonal cylinders.\",\n \"S130: contact the test electrode of the transfer device with the micro element electrode to apply test voltage on the test circuit to form a test hoop for testing the micro element and obtaining defect pattern of the micro element of the carrier substrate.\",\n \"Through the test circuit of the transfer device, when the pick-up head array contacts with the micro element, the test electrode connects to the micro element electrode to form a test hoop.\",\n \"During transferring of the micro element, test the micro element to obtain defect pattern of the micro element for selective pick-up of qualified micro elements or unqualified micro elements.\",\n \"The embodiment for a transfer method of micro element for prior removal of defects is described in detail with reference to figures below.\",\n \"FIG.\",\n \"20 is a schematic diagram of a transfer method of the micro element according to the sixth preferred embodiment of the present invention, comprises steps S210-S250.For example, S210 includes provide a transfer device, including pick-up head array and test circuit, test circuit including a series of sub-test electrodes, each sub-test circuit having at least two test electrodes.\",\n \"S220 includes positioning the transfer device on the micro element connected to the carrier substrate.\",\n \"S230 includes contacting the test electrode of the transfer device with the micro element electrode to apply test voltage on the test circuit to form a test hoop for testing the micro element and obtaining defect pattern of the micro element of the carrier substrate.\",\n \"S240 includes using the pick-up head array to pick up acceptable micro elements from the carrier substrate S250 includes releasing the micro elements to the receiving substrate Referring to FIG.\",\n \"21, provide a transfer device 1100, and position it on the micro element 1200 which is connected to the carrier substrate 1300.Brief description is given below taking the transfer device 1100 of the first preferred embodiment of the present invention as an example.\",\n \"Place the micro element on the carrier substrate 1300, with electrodes upwards, and the test electrodes 1134A and 1134B of the transfer device 1100 align with the micro element electrodes 1120A and 1120B respectively.\",\n \"For simplification, the figure only shows four micro elements 1201-1204.Referring to FIG.\",\n \"22, contact the pick-up head 1120 of the transfer device with the micro element.\",\n \"The test electrode is connected to the micro element electrode, and applies voltage on both ends of the test electrode to form a test loop for testing the micro element and obtaining defect patterns of the micro element.\",\n \"For example, photoelectric parameters of the micro element 1204 are qualified, and photoelectric parameters of the micro element 1201-1203 are not qualified.\",\n \"Referring to FIG.\",\n \"23, by controlling the pick-up head array of the transfer device, selectively pick up qualified micro elements 1201-1203 on the carrier substrate 1300.In this embodiment, the micro element array has 10 μm interval, wherein, each micro element has 2 μm interval and 8 μm maximum width.\",\n \"Top surface of each micro element has a width approximating to 8 μm, and width of the surface of the corresponding pick-up head for contacting with the micro element is near 8 μm or less, thus avoiding unintentional contact with adjacent micro LED device.\",\n \"The embodiments of the present invention can be any appropriate sizes, and not limited to such sizes.\",\n \"Referring to FIG.\",\n \"24, release the micro elements 1201-1203 on the acceptor substrate 1400.The acceptor substrate can be automotive glass, glass sheet, flexible electronic substrate, such as flexible film of path, display back plate, solar glass, metal, polymer, polymer compound and glass fiber.\",\n \"In this embodiment, when the transfer device contacts with the micro element array, the test circuit of the transfer device tests the micro element to obtain defect pattern of the micro element array.\",\n \"Then, selectively pick up qualified micro elements to effectively prevent defect micro elements from transfer-printing to the acceptor substrate of terminal applications such as the display backboard during transformation.\",\n \"FIG.\",\n \"25 is a flow diagram of a transfer method of the micro element according to the seventh preferred embodiment of the present invention, mainly comprises steps S310-S350, wherein, steps S310-S330 are same as steps S210-S230.Brief description is given below targeting at steps S340-S350.Referring to FIG.\",\n \"26, by controlling the pick-up head array of the transfer device, selectively pick up unqualified micro elements 1204 on the carrier substrate 1300; referring to FIG.\",\n \"27, release unqualified micro elements 1204 on the acceptor substrate 1500.In this embodiment, the acceptor substrate 1500 can be any recovery device for recovering and placing the unqualified micro element.\",\n \"In this embodiment, before transfer of the micro element, at first, test the micro element array with the test circuit of the transfer device, and transfer it to the recovery device.\",\n \"Therefore, those remained on the micro element of the carrier substrate are qualified products for prior removal of unqualified micro elements.\",\n \"FIG.\",\n \"28 is a flow diagram of a transfer method of the micro element according to the eighth preferred embodiment of the present invention, mainly comprises steps S410-S450, wherein, steps S410-S430 are basically same as steps S210-S230.Brief description is given below targeting at steps S440-S450.Referring to FIG.\",\n \"29, by controlling the pick-up head array of the transfer device, selectively pick up the micro elements 1201-1204 on the carrier substrate 1300; referring to FIG.\",\n \"30, by controlling, selectively release unqualified micro elements 1204 on the first acceptor substrate 1500; referring to FIG.\",\n \"31, release qualified micro elements 1201-1203 on the second acceptor substrate 1400.In this embodiment, the first acceptor substrate 1500 can be any recovery device for recovering and placing the unqualified micro element; the second acceptor substrate 1400 can be a flexible electronic substrate, such as a flexible film with a circuit, display back plate, and the like.\",\n \"In S450 of this embodiment, it is acceptable to release qualified micro elements 1201-1203 on the second acceptor substrate 1400 and then release unqualified micro elements 1204 on the first acceptor substrate 1500.FIG.\",\n \"32 is a flow diagram of a transfer method of the micro element according to the ninth preferred embodiment of the present invention, mainly comprising steps S510-S570, wherein, steps S510-S520 are basically same as S210-S220.Brief description is given below targeting at steps S530-S570.Referring to FIG.\",\n \"33, use the pick-up head array of the transfer device to selectively pick up the micro elements 1201-1204 on the carrier substrate 1300; referring to FIG.\",\n \"34, release the micro elements 1201-1204 on the second acceptor substrate 1400.The pick-up head of the transfer device keeps contact with the micro element, and the test electrode of the transfer device contacts with the micro element electrode; referring to FIG.\",\n \"35, apply voltage on the test electrode, and each micro element 1201-1204 forms a sub-test hoop for testing and obtaining the defect pattern of the micro element.\",\n \"For example, photoelectric parameters of the micro element 1201 are unqualified (namely, the defect micro element), and photoelectric parameters of the micro element 1202-1204 are qualified; referring to FIG.\",\n \"36, use the pick-up head array of the transfer device to selectively pick up the defect micro element 1201 of the second acceptor substrate 1400; referring to FIG.\",\n \"37, release the defect micro element 1201 on the first acceptor substrate 1500, wherein, the first acceptor substrate 1500 can be any recovery device for recovering and placing the unqualified micro element; and the second acceptor substrate 1400 is a flexible electronic substrate, such as a flexible film with a circuit, display back plate, and the like.\",\n \"The pick-up head arrays according to the above embodiments pick up or release micro elements through electrostatic force, Van der Waals force and vacuum adsorption force.\",\n \"The transfer method of the micro element of each embodiment takes the transfer device 1100 disclosed in FIG.\",\n \"1 as an example.\",\n \"However, this invention is not limited to this transfer device.\",\n \"For micro elements with different electrode structures, the transfer devices of different structures can be selected.\",\n \"In the transfer method of the micro element, the micro element arrays can be tested and transfer printed for several times through the transfer device.\",\n \"The transfer method for the micro element according to aforesaid embodiment can also be used for fabricating electronic device, or be widely applied in electronic devices like mobile phone, tablet PC, and the like.\",\n \"Despite the description of exemplary embodiments of the present invention, it should be understood that it is not intended to limit the scope of the invention to the particular form set forth.\",\n \"On the contrary, alternatives and modifications can be made by the persons skilled in the art without departing from the spirit and scope of the invention as defined by the appended claims.\"\n ]\n]"},"source":{"kind":"string","value":"Patent_15871982"}}},{"rowIdx":4493971,"cells":{"text":{"kind":"list like","value":[["Paging and Random Access Response (RAR) Scheduling and DCI Format","Methods and apparatus are provided for paging and random access response (RAR) scheduling and downlink control information (DCI) for a user equipment (UE).","In one novel aspect, an SI-paging and a call-paging are transmitted separately, and scheduled by SI-Paging-DCI and call-Paging-DCI respectively.","In one embodiment, a special PO is introduced for stand-alone SI-Paging scheduled by SI-Paging-DCI, and the special PO is different from the PO for call-Paging.","In another novel aspect, SI-Paging is scheduled together with call-paging in the same PDSCH scheduled by call-Paging-DCI.","In one embodiment, the SI-paging carries a value tag and a bitmap, wherein the value tag indicates whether any SI updates, and the bitmap indicates which one or more SIs updates.","In another embodiment, the SI-Paging carries several valuetags, and the number of valuetag corresponds to the number of SI.","The UE compares a current valuetag to a stored valuetag to verify whether a SI changes."],["1.A method, comprising: detecting a first extended paging occasion (PO) for a paging message by a low-cost (LC) user equipment (UE) in a wireless network based on a UE state; determining the first extended PO is a SI-paging PO or a call-paging PO; decoding a SI-paging DCI to obtain a SI-paging message to obtain a change notification of SI if the first extended PO is determined as the SI-paging PO; and decoding a call-paging DCI to obtain scheduling information of a call-paging massage if the first extended PO is determined as a call-paging PO.","2.The method of claim 1, wherein the paging message is multi-casted to a plurality of UEs, and wherein the paging message carries a group identifier configured for the plurality of UEs.","3.The method of claim 2, wherein the group identifier is a logical UE ID.","4.The method of claim 2 wherein group identifier is group-specific paging radio network temporary identifier (P-RNTI).","5.The method of claim 2, wherein the plurality of UEs is configured with the same group identifier if the plurality of UEs have the same coverage enhancement (CE) level.","6.The method of claim 2, wherein the paging message sent repeatedly with a repetition number, and wherein the repetition number is determined by the maximum CE level of the plurality of UEs.","7.The method of claim 1, wherein the paging message is control information carrying the SI-Paging message or scheduling information for the call-Paging message.","8.The method of claim 1, wherein the SI-paging message comprises a value tag and a bitmap, wherein the value tag indicates whether any SI updates, and the bitmap indicates which one or more SIs update.","9.The method of claim 8, wherein a dedicated RNTI is allocated for the SI-paging-DCI.","10.The method of claim 1, wherein the call-paging DCI scheduled by a MTC physical downlink control channel (MPDCCH), and the call-paging message is carried by a physical downlink shared channel (PDSCH).","11.The method of claim 1, wherein a resource allocation indication is indicated in the call-paging DCI, wherein the resource allocation indication comprising at least one of the following: indicating a frequency location in the narrow band, or indicating the resource allocation within a known narrow band.","12.The method of claim 1, wherein an additional extended call-Paging PO is indicated by the call-paging-DCI.","13.A method, comprising: detecting a first extended PO for a paging message by a low-cost (LC) user equipment (UE) in a wireless network based on a UE state; perform blind decoding according to SI-paging DCI format and call-paging DCI format; obtaining the SI change notification if blind decoding successfully with the SI-paging-DCI format; obtaining a scheduling information of SI-paging message and the call-paging message if decoding successfully with the call-paging-DCI format.","14.The method of claim 13, the paging message is the SI-Paging-DCI or control information scheduling both the SI-Paging and the call-Paging.","15.A method, comprising: determining a coverage enhancement (CE) level by a user equipment (UE) based on measurement in a wireless communication network; determining a position in a time domain to monitor control information for random access response (RAR); determining whether a RAR mode is a single RAR for a single UE or a multiple RAR for a plurality of UEs; and decoding the RAR based on the CE level and the RAR mode.","16.The method of claim 15, wherein the RAR-DCI has the same size for both enhanced coverage (CE) mode and normal coverage (NC).","17.The method of claim 15, wherein a transmit power control (TPC) command field is overloaded with a repetition number if the CE level indicates an enhanced coverage (CE) mode, wherein the repetition number indicates a number of repeated transmissions configured for the CE level to transmit Msg 3.18.The method of claim 15, wherein a backoff indicator (BI) is not transmitted within the RAR or the RAR-DCI, but configured by a higher layer.","19.The method of claim 15, wherein a BI is within RAR-DCI if there is no RAR transmitted, otherwise, the BI is within RAR carried by PDSCH.","20.The method of claim 15 wherein a BI is transmitted within a RAR-DCI."],[" BACKGROUND Third generation partnership project (3GPP) and Long Term Evolution (LTE) mobile telecommunication systems provide high data rate, lower latency and improved system performances.","Such systems are optimized for regular data communications, wherein there is no need for repeatedly retransmissions.","However, in some situations, repeatedly retransmissions are needed.","For example, some UEs, in the basements of residential buildings or locations shielded by foil-backed insulation, metalized windows or traditional thick-walled building construction, may experience significantly larger penetration losses on the radio interface than normal LTE devices.","More resources/power are needed to support these UEs in the extreme coverage scenario.","Repetition has been identified as a common technique to bridge the additional penetration losses than normal LTE devices.","In another example, Machine-Type Communication (MTC) is an important revenue stream for operators and has a huge potential from the operator perspective.","Lowering the cost of MTC user equipment (UEs)/devices is an important enabler for the implementation of the concept of “Internet of Things” (IOT).","The LC-MTC/LC-UE has limited bandwidth.","The limited bandwidth and the need to repeatedly transmission require enhancement for paging and RAR procedures.","Improvements and enhancements are needed for paging and RAR scheduling for LC-UEs."],[" SUMMARY Methods and apparatus are provided for paging and RAR scheduling, and corresponding DCI format for low cost UEs.","In one novel aspect, an SI-paging (system information-paging) and a call-paging are transmitted separately, and scheduled by SI-Paging-DCI and call-Paging-DCI respectively.","In one embodiment, a special PO is introduced for stand-alone SI-Paging scheduled by SI-Paging-DCI, and the special PO is different from the PO for call-Paging.","In another novel aspect, SI-Paging is scheduled together with call-paging in the same PDSCH scheduled by call-Paging-DCI.","In one embodiment, the SI-paging carries a value tag and a bitmap, wherein the value tag indicates whether any SI updates, and the bitmap indicates which one or more SIs updates.","In another embodiment, the SI-Paging carries several valuetags, and the number of valuetag corresponds to the number of SI.","The UE compares a current valuetag to a stored valuetag to verify whether a SI changes.","In another novel aspect, the RAR scheduling and RAR-DCI format is based on a CE level of the UE.","In one embodiment, based on DL measurement, the UE determines a coverage enhancement (CE) level and select a preamble for this CE level in a wireless communication network and determines whether a RAR mode is a single RAR for a single UE or a multiple RAR for a plurality of UE.","The UE decodes the RAR based on the CE level of the UE and the RAR mode.","In one embodiment, the RAR-DCI has the same size for both coverage enhanced or coverage extension (CE) mode, and normal coverage (NC)mode.","In another embodiment, the transmit power control (TPC) command field is overloaded with a repetition number if the CE level indicates a coverage enhanced/extension(CE) mode, wherein the repetition number indicates a number of repetitions for the CE level.","Further details and embodiments and methods are described in the detailed description below.","This summary does not purport to define the invention.","The invention is defined by the claims."],["CROSS REFERENCE TO RELATED APPLICATIONS This application is filed under 35 U.S.C.","§111(a) and is based on and hereby claims priority under 35 U.S.C.","§120 and §365(c) from International Application No.","PCT/CN2015/087006, with an international filing date of Aug. 14, 2015.This application is a continuation of International Application No.","PCT/CN2015/087006, which is pending as of the filing date of this application, and the United States is a designated state in International Application No.","PCT/CN2015/087006.The disclosure of each of the foregoing documents is incorporated herein by reference.","TECHNICAL FIELD The disclosed embodiments relate generally to wireless communication, and, more particularly, to paging and random access response (RAR) scheduling and downlink control information (DCI).","BACKGROUND Third generation partnership project (3GPP) and Long Term Evolution (LTE) mobile telecommunication systems provide high data rate, lower latency and improved system performances.","Such systems are optimized for regular data communications, wherein there is no need for repeatedly retransmissions.","However, in some situations, repeatedly retransmissions are needed.","For example, some UEs, in the basements of residential buildings or locations shielded by foil-backed insulation, metalized windows or traditional thick-walled building construction, may experience significantly larger penetration losses on the radio interface than normal LTE devices.","More resources/power are needed to support these UEs in the extreme coverage scenario.","Repetition has been identified as a common technique to bridge the additional penetration losses than normal LTE devices.","In another example, Machine-Type Communication (MTC) is an important revenue stream for operators and has a huge potential from the operator perspective.","Lowering the cost of MTC user equipment (UEs)/devices is an important enabler for the implementation of the concept of “Internet of Things” (IOT).","The LC-MTC/LC-UE has limited bandwidth.","The limited bandwidth and the need to repeatedly transmission require enhancement for paging and RAR procedures.","Improvements and enhancements are needed for paging and RAR scheduling for LC-UEs.","SUMMARY Methods and apparatus are provided for paging and RAR scheduling, and corresponding DCI format for low cost UEs.","In one novel aspect, an SI-paging (system information-paging) and a call-paging are transmitted separately, and scheduled by SI-Paging-DCI and call-Paging-DCI respectively.","In one embodiment, a special PO is introduced for stand-alone SI-Paging scheduled by SI-Paging-DCI, and the special PO is different from the PO for call-Paging.","In another novel aspect, SI-Paging is scheduled together with call-paging in the same PDSCH scheduled by call-Paging-DCI.","In one embodiment, the SI-paging carries a value tag and a bitmap, wherein the value tag indicates whether any SI updates, and the bitmap indicates which one or more SIs updates.","In another embodiment, the SI-Paging carries several valuetags, and the number of valuetag corresponds to the number of SI.","The UE compares a current valuetag to a stored valuetag to verify whether a SI changes.","In another novel aspect, the RAR scheduling and RAR-DCI format is based on a CE level of the UE.","In one embodiment, based on DL measurement, the UE determines a coverage enhancement (CE) level and select a preamble for this CE level in a wireless communication network and determines whether a RAR mode is a single RAR for a single UE or a multiple RAR for a plurality of UE.","The UE decodes the RAR based on the CE level of the UE and the RAR mode.","In one embodiment, the RAR-DCI has the same size for both coverage enhanced or coverage extension (CE) mode, and normal coverage (NC)mode.","In another embodiment, the transmit power control (TPC) command field is overloaded with a repetition number if the CE level indicates a coverage enhanced/extension(CE) mode, wherein the repetition number indicates a number of repetitions for the CE level.","Further details and embodiments and methods are described in the detailed description below.","This summary does not purport to define the invention.","The invention is defined by the claims.","BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings, where like numerals indicate like components, illustrate embodiments of the invention.","FIG.","1 illustrates an exemplary wireless network 100 with enhanced paging and RAR scheduling for LC-UEs in accordance with embodiments of the current invention.","FIG.","2 illustrates exemplary paging groups to page a group of UEs by the same paging message in accordance with embodiments of the current invention.","FIGS.","3A and 3B show exemplary diagrams of the SI value tag and bitmap for SI-paging message in accordance with embodiments of the current invention.","FIG.","4 shows exemplary diagrams of DCI format for call-paging in accordance with embodiments of the current invention.","FIG.","5 shows an exemplary diagram for a paging procedure with additional Paging Occasion in accordance with the current invention.","FIG.","6 shows an exemplary diagram for the first stage of procedure when the SI-paging and call-paging are sent separately in accordance with embodiments of the current invention.","FIG.","7 shows an exemplary diagram for the second stage of SI-paging procedure when the SI-paging and call-paging are sent separately in accordance with embodiments of the current invention.","FIG.","8 shows an exemplary diagram for the second stage of call-paging procedure when the SI-paging and call-paging are sent separately in accordance with embodiments of the current invention.","FIG.","9 shows an exemplary flow chart when the SI-paging and call-paging are sent together in accordance with embodiments of the current invention.","FIG.","10 illustrates an exemplary diagram of the DCI for the single RAR in accordance with embodiments of the current invention.","FIG.","11A illustrates an exemplary diagram of the DCI for the multiple RARs in accordance with embodiments of the current invention.","FIG.","11B illustrates a comparison table for different scenarios for a multiple RAR DCI in accordance with embodiments of the current invention.","FIG.","12 shows an exemplary diagram for the first stage of procedure of RAR process for the single RAR or multiple RAR in accordance with embodiments of the current invention.","FIG.","13 shows an exemplary diagram for the second stage for the single RAR procedure in accordance with embodiments of the current invention.","FIG.","14 shows an exemplary diagram for the second stage for the multiple RAR procedure in accordance with embodiments of the current invention.","FIG.","15 illustrates an exemplary flow chart for paging scheduling and the DCI format by transmitting the SI-paging and the call-paging separately in accordance with embodiments of the current invention.","FIG.","16 illustrates an exemplary flow chart for paging scheduling and the DCI format by transmitting the SI-paging and the call-paging together in accordance with embodiments of the current invention.","FIG.","17 illustrates an exemplary flow chart for RAR scheduling based on the CE level in accordance with embodiments of the current invention.","DETAILED DESCRIPTION Reference will now be made in detail to some embodiments of the invention, examples of which are illustrated in the accompanying drawings.","Currently, the traditional paging scheduling and RAR scheduling are not designed for repeatedly transmissions, wherein paging is to indicate system information (SI) modification and to page idle UE to set up RRC connection, and RAR is a response from eNB for UE transmitted preamble.","For example, LC-UE does not support PDCCH, instead, MTC PDCCH (M-PDCCH) is used.","Further, UEs still have to blind decode all system information to confirm which system information have modifies, after receiving a paging message for SI update notification.","It will introduce much power consumption for LC MTC UEs, which are expected to have a 10-year battery life.","To facilitate description, the information within a paging message to indicated system information modification is named as SI-paging, and the information within a paging message to initiate RRC connection setup is named as Call-paging FIG.","1 illustrates an exemplary wireless network 100 with enhanced paging and RAR scheduling for LC-UEs in accordance with embodiments of the current invention.","Wireless communications system 100 includes one or more wireless networks, and each of the wireless communication network has fixed base infrastructure units, such as 105 and 106.The base units may also be referred to as an access point, an access terminal, a base station, eNB, or by other terminology used in the art.","Each of the base stations 105 and 106 serves a geographic area.","The geographic area served by wireless communications stations 105 and 106 overlaps in this example.","UEs 101 and 102 in the wireless network 100 are served by base station 105.Other UEs, such as UEs 103, 107 and 108, are served by a different base station 106.In one novel aspect, UEs 101, 102, 103, 107 and 108 can be LC-UEs, and the LC-UEs can have different coverage enhancement (CE) level to support coverage extension.","In one embodiment, LC-UEs 101, 102, 103, 107 and 108 are real LC-MTC UEs actually.","In another embodiment, LC-MTC UEs 101, 102, 103, 107 and 108 are regular UEs that are served/regarded as LC UEs.","For example, regular UEs in CE mode can be served as LC UEs.","To page a group of UEs with less resource overhead and less power consumption, a single paging message is multi-casted to the group of UEs identified by a group ID in one embodiment.","That is there is only one ID to page the group of UEs.","In another embodiment, the single paging message for multiple UEs is a function of a group-specific P-RTNI.","In this embodiment, the single paging message can be a sequence generated from the P-RNTI, and corresponding UEs determine they are paged if such sequence exists.","The group-specific P-RNTI is higher layer configured by broadcast in one design option.","For such single paging message without carrying multiple UE specific IDs, the grouping can be (re)configured.","In one embodiment, UEs with similar CE levels are grouped together.","In another embodiment, UEs with same service/traffic type within a specific area is grouped and identified by a group ID.","Then, the group UEs in one single paging message can of the same CE level or different CE level.","If the CE level is similar, a repetition number for retransmission is determined based on the common CE level for the paging group in one option.","In another option, the paging has a mixed level of CE value.","The repetition number is, thereby, the one corresponding to the highest CE level in the paging group.","FIG.","1 further shows simplified block diagrams of UE 101 and base station 105 in accordance with the current invention.","Base station 105 has an antenna array 126 comprising one or more antennas, which transmits and receives radio signals.","A RF transceiver module 123, coupled with the antenna, receives RF signals from antenna array 126, converts them to baseband signals and sends them to processor 122.RF transceiver 123 also converts received baseband signals from processor 122, converts them to RF signals, and sends out to antenna array 126.Processor 122 processes the received baseband signals and invokes different functional modules to perform features in base station 105.Memory 121 stores program instructions and data 124 to control the operations of base station 102.Base station 105 also includes a set of control modules, such as a paging and RAR handler 125 that carry out functional tasks to configure, schedule, execute and communicate with the UE 101 for paging and RAR related tasks.","UE 101 has an antenna array 135 with single antenna, which transmits and receives radio signals.","A RF transceiver module 134, coupled with the antenna, receives RF signals from antenna array 135, converts them to baseband signals and sends them to processor 132.RF transceiver 134 also converts received baseband signals from processor 132, converts them to RF signals, and sends out to antenna 135.Processor 132 processes the received baseband signals and invokes different functional modules to perform features in mobile station 101.Memory 131 stores program instructions and data 136 to control the operations of mobile station 101.UE 101 also includes a set of control modules that carry out functional tasks.","A paging handler 191 handles paging monitoring for both SI-paging and Call-paging.","A RAR handler 192 handles RAR procedure based on the CE level for both the single RAR and multiple RAR.","In one novel aspect, a paging message is multi-casted to a plurality of UEs.","The group of UEs can be paged by one same group ID with a very small payload size.","The power consumption and resource efficiency are improved, especially for LC-UEs with repeatedly transmissions.","FIG.","2 illustrates exemplary paging groups to page different group of UEs by the same single paging message in accordance with embodiments of the current invention.","A base station 209 covers a plurality of UEs with different CE levels.","FIG.","2 shows four exemplary diagrams of different grouping for the paging message according to different rules.","In one embodiment, UEs with the same service type but different CE levels are grouped together, and configured by a same group ID.","As shown, paging group 210 includes four UEs, UE 211, UE 212, UE 213, and UE 214 with CE levels being CE level-1, CE level-3, CE level-4 and CE level-1, respectively.","All the UEs in the same paging group have the same group ID-1.A paging message 201 is multi-casted with the group ID-1.The one paging message 201 covers the four UEs in the same paging group 210.In one embodiment, repeatedly transmissions are required for UE in CE mode.","In one option, the number of repetition is based on the higher CE level.","In this example, each UE in group-1, UEs 211, 212, 213 and 214, receives repetition transmission with a repetition number corresponding to a CE level-4, which is the highest CE level in group-1.Such grouping can preconfigured by the network or by higher layer signaling.","In another embodiment, the UEs with the same CE-level are grouped together.","A paging group 220, including UE 221, 222, and 223 are grouped together with the same paging group ID-2.Each UE in paging group 220 has the same CE level, i.e., CE level-1.A paging message 202 is multi-casted to all UEs in paging group 220 with the same repetition number based the common CE level (CE level-1).","In other embodiments, a group-specific P-RNTI is used to identify a paging group.","A paging group 230 includes UEs 231, 232, and 233, with CE level-1, CE level-5 and CE level-2, respectively.","A paging message 203 is multi-casted to each UE in paging group 230 with a group-specific P-RNTI, P-RNTI-1.The repetition number is set to be corresponding to the highest CE level of the group, which is CE level-5.In yet another embodiment, the UEs with the same CE level are grouped together by another group-specific P-RNTI, P-RNTI-2.As shown, a paging group 240 includes UEs 241 and 242, each with the same CE level-2.A paging message 204 is multi-casted to each UE in paging group 240 with P-RNTI-1, wherein the repetition number is set to be correspondence to CE level-1, while a paging message 203 is transmitted to each UE within paging group 230 with P-RNTI-2, wherein the repetition number is set to be corresponding to CE level-5, the highest CE level within paging group 230.To reduce UE power consumption, it's expected that SI-paging can indicate which system information (including M-MIB (MTC MIB) and M-SIB (MIC SIB) information for LC MTC UEs) will update.","In one case, that SI-paging is always transmitted regardless whether there are SI changes in one embodiment.","In another embodiment, SI-paging is transmitted only when there will be some update to some system information.","In one novel aspect, the SI-paging comprises a bitmap and a value tag.","The bitmap indicates which system information changes and the value tag indicates whether there is any M-SI (MTC-SI) updates.","In this novel aspect, the length of the bitmap is equal to the number of M-SI messages for MTC UEs in one embodiment.","Here, change of M-MIB is not indicated.","In another embodiment, the length of the bitmap is equal to the number of SI message for MTC UEs plus 1 to indicate the update of both M-MIB and M-SI.","The value range of value tag can be denoted as an integer with Y bits, while candidate value for Y is {4, 5}.","In another novel aspect, the SI-Paging comprises several value tags and each value tag indicates whether corresponding system information will update.","Here, the total value tag number is equal to the bitmap length in the on novel aspect, and the value range of each value tag equals to the value tag in the one novel aspect.","FIG.","3A shows an exemplary diagram of the SI value tag and bitmap for SI-paging message in accordance with embodiments of the current invention.","In one embodiment, within SI-paging, there is an X-bit value tag 301 and Y-bit bitmap 302.In one embodiment, value tag 301 has five bits and indicates any changes to some system information.","The UE compares the received value tag with the value tag it receives last time.","If value tag 301 changes, it indicates there exists update to system information.","The UE, subsequently, checks the Y-bit bitmap 302 to determine which M-SI or M-MIB will update.","Bitmap 302 indicates one M-SI or M-MIB update by set the corresponding bit in bitmap 302, for example, to 1.FIG.","3B shows an exemplary diagram of the SI value tag and bitmap for SI-paging message in accordance with embodiments of the current invention.","In this figure, there are Y value tags {303, 304, 305, 306} within the SI-Paging.","In this example, M-MIB change is indicated by a value tag 303 within SI-paging.","Further, there are 3 M-SI messages for MTC UEs, and each M-SI change notification is denoted as value tag 304, 305, 306, respectively.","If the value of any value tag changes, the UE can determine that the corresponding system information changes or will change.","For LC MTC UEs, the format of DCI for scheduling a paging message is different from legacy DCI format.","One consideration is Resource Allocation (RA) field.","Due to bandwidth reduction, resources are restricted to a limited size, e.g., 6 PRB pairs (1.4 MHz).","Then, a RA filed should indicate which narrow band is used for paging message transmission, or how many resources are allocated within a narrow band.","In a first embodiment, only a narrow band location for the paging message is indicated within the RA field, wherein it's assumed that all resources within the indicated narrow band are used for transmission.","In a second embodiment, resources within a known narrow band are indicated by the RA field, wherein the known narrow band is (re)configured by higher layer, or predefined, or derived from a rule.","In a third embodiment, the RA filed indicates a narrow band location and resource allocation within the indicated narrow band.","The length of RA field depends on the whole channel bandwidth.","Taking 20 MHz bandwidth as an example, the RA filed size can be 4 bits under the first embodiment, and 5 bits under the second embodiment considering 1.4 MHz limitation, and 9 bits in the third embodiment.","Further, the modulation order may be restricted for MTC UEs with payload size limitation and cost reduction.","For example, 16 QAM can be supported in normal CE mode, and only QPSK is applied in the CE mode.","Then, Modulation And Coding Scheme (MCS) field can be 4 bits or 5 bits.","Also, the payload size can be larger if there are multiple UEs to be paged within one paging message.","The payload size indicated by the MCS field is the exact size of the paging message.","In another embodiment, the payload size for the paging message is the indicated payload size by the MCS field plus the payload size of SI-paging.","Thirdly, a field for repetition number indication is also needed in the CE mode.","In one embodiment, a repetition number is explicitly given by the repetition number field.","It can be interpreted as no coverage extension in case the indicated repetition number is 1.In another embodiment, an coefficient is given within the repetition number field, and the UE derives the exact repetition number by multiplexing the coefficient with a basic repetition number.","Here, the basic repetition number is broadcast or predefined.","Then, a DCI format for LC MTC UEs to receive paging message may comprise modulation coding scheme (MCS) field, RA field, and repetition indication field at least.","Considering blocking rate or in case of massive number of UE, one more field for dynamic extended PO allocation can be comprised to indicate an additional extended PO dynamically.","For example, a value 1 for this single bit can be interpreted that there is an additional extended PO.","To facilitate description, a current extended PO to receive/decode control information is named as a first extended PO, and the indicated additional extended PO from the decoded DCI at the first extended PO can be also named as a second extended PO.","Then, if one UE finds it is not paged within current paging message, which is scheduled by the control information at the first extended PO, the UE can try to decode another DCI for paging message at the indicated second extended PO.","In one embodiment, the additional PO indication always exist.","Then, UE always blind decodes one DCI size, i.e.","the Call-paging DCI size.","In another embodiment, the additional extended PO indication is optional.","Then, UEs should blind decode two different DCI sizes.","The position of the indicated additional extended PO can be determined by adding a basic time distance predefined according to different CE levels to the determined first extended PO.","FIG.","4 shows exemplary diagrams of DCI format to schedule paging message to LC MTC UEs in accordance with embodiments of the current invention.","A paging DCI 400 includes a MCS field 401, a RA field 402, a repetition number field 403, and an additional extended PO field 404.MCS field 401 can be 4 bits or 5 bits depending on a UE number within a paging message and the CE level.","In one embodiment, a 4-bit MCS field is for QPSK; while a 5-bit MCS field is for 16 QPSK.","RA field 402 has 4 bits, 5 bits or 9 bits under different embodiments.","Repetition number field 403 can be a 2-bit field or a 3-bit field.","The 1-bit additional PO field 404 indicates whether there is another available extended PO for a paging message following current determined extended PO.","FIG.","5 shows an exemplary diagram for a paging procedure with additional extended PO in accordance with the current invention.","At step 501, the UE decodes a DCI for paging messages at an extended PO 521.The DCI in step 501 indicates one additional extended PO.","At step 502, the UE receives a paging message according to the DCI decoded in step 501.At step 510, based on the additional extended PO indicated in step 501, the UE moves to decode another DCI at the additional extended PO 522 (step 503).","At step 503, the UE decodes the second DCI for another paging monitoring.","Based on the decoded DCI at step 503, the UE decodes another paging message at step 504.In legacy system, paging occasion (PO) is a subframe carrying both the control information and the paging message.","Considering the characteristics of LC MTC UEs, UEs may decode control information scheduling a paging message in one subframe, and receive the corresponding paging message in another subframe, since the control information and the paging message may locate in different narrow bands.","Further, in case of CE mode with repetitions, UEs should also decode the control information first within multiple subframes, before decoding the corresponding paging message.","Therefore, the UE should determine a starting point to decode control information when monitoring the paging message.","In this invention, an extended PO is introduced for paging message monitoring for LC MTC UEs, wherein the extended PO is a starting point or a position in time domain to decode control information scheduling a paging message comprising SI-paging and Call-paging.","Call-paging is to initiate RRC connection, so it is only monitored by idle UEs without RRC connection.","SI-paging is for all UEs to verify there is system information update.","In this invention, connected UEs, i.e., UEs with RRC connection, determine to receive and decode corresponding system information, after receiving the SI-paging, in one embodiment.","In another embodiment, updated information elements (IEs) within corresponding system information is transmitted to UEs specifically by network, and the received information will apply at next modification period.","Note that not the whole of one or more M-SI messages are transmitted, but only the updated part of each M-SI message is transmitted.","In one embodiment, the SI-paging and the Call-paging are transmitted and received separately in different time positions.","Specifically, the SI-paging is carried by a SI-paging DCI within MTC PDCCH (MPDCCH) transmitted at a dedicated extended PO for SI-paging (i.e., SI-paging-PO).","The Call-paging is carried by the PDSCH scheduled by a Call-paging-DCI within MPDCCH which is transmitted from another extended PO for Call-paging (i.e., Call-paging-PO).","In this novel aspect, the UE checks whether there is SI updates by detecting the SI-paging, when the UE is in the connected state.","When the UE is the IDLE mode, the UE monitors Call-paging or SI-paging at each different extended PO.","In another embodiment, the SI-paging and the Call-paging are scheduled together at a same extended PO.","Specifically, The SI-paging is transmitted by a SI-paging-DCIif no Call-paging is transmitted, and the SI-paging is carried by the PDSCH scheduled by the Call-paging-DCI, if there is call-paging transmission.","In this novel aspect, when the UE is in the connected state, the updated IEs within corresponding system information message are transmitted to UE specifically by the eNB scheduling.","When the UE is in the IDLE mode, the UE monitors both call-paging and SI-paging at each extended PO.","FIG.","6 shows an exemplary diagram for the first stage of procedure when the SI-paging and call-paging are scheduled separately at different extended POs in accordance with embodiments of the current invention.","At step 601, the UE determines a time position, e.g., an extended PO, to monitor the paging information.","At step 602, the UE determines whether it is in the IDLE state.","If step 602 determines no, the UE moves to step 604 and blindly decodes the SI-paging DCI with the SI-paging DCI size within time-frequency resources, since connected UE only monitors SI-paging.","The UE subsequently continues to step 610 to deal with the SI-paging message.","If step 602 determines yes, the UE moves step 603.At step 603, the UE determines if the determined extended PO is used for SI-paging.","If the step 603 determines yes, the UE moves to step 604 and continues.","If the step 603 determines no, i.e., the determined extended PO is used for Call-paging, which means the current extended PO is a Call-paging PO, the UE blindly decodes the DCI with Call-paging DCI size within a determined set of time-frequency resources to obtain a location for Call-paging (step 605).","The UE subsequently continues to step 620 to deal with the Call-paging message.","FIG.","7 shows an exemplary diagram for the second stage of SI-paging procedure when the SI-paging and Call-paging are scheduled separately at different extended POs in accordance with embodiments of the current invention.","At step 701, followed by step 610 of blindly decoding SI-paging-DCI, the UE determines if the blind decoding is successful by checking the CRC.","If step 701 determines no, the UE moves to step 703 and waits for the next SI-paging PO, wherein assuming SI-Paging is not transmitted at each possible SI-paging PO.","If step 701 determines yes the UE moves step 702 and obtains change notification of system information.","Based on step 702, the UE, at step 704, decodes and updates corresponding M-MIB or M-SI message at proper time positions.","FIG.","8 shows an exemplary diagram for the second stage of Call-paging procedure when the SI-paging and call-paging are scheduled separately in different extended POs in accordance with embodiments of the current invention.","At step 801, followed by step 620 of blindly decoding the Call-paging-DCI, the UE determines if the decoding is successful by checking the CRC.","If step 701 determines no, the UE moves to step 806 and waits to try the next Call-paging PO.","If step 801 determines yes the UE moves to step 802.At step 802, the UE decodes the PDSCH according to the decoded DCI.","The UE, subsequently, checks whether it has been paged in step 803.If step 803 determines yes, the UE moves to step 804, and obtains paging information and prepares for the RRC connection setup.","If step 803 determines no, there are two options for the next step.","In the first option, there is no additional extended PO for the UE, the UE will stop the paging process and moves to wait for the next extended PO.","In the second option, the UE moves to step 810 and checks if there is additional extended PO indicated by the decoded Call-paging-DCI.","If step 810 determines no, the UE will stop the paging process and moves to wait for the next extended PO.","If step 810 determines yes, the UE will go back to step 605 to blindly decode for the Call-paging-DCI at the additional extended PO.","FIG.","9 shows an exemplary flow chart when the SI-paging and call-paging are scheduled together at a same extended PO in accordance with embodiments of the current invention.","First in step 911, the UE determines a time position, i.e.","PO to monitor paging information.","Then in step 912, the UE determines the frequency location to receive Paging DCI and blind decode two different DCI sizes (SI-Paging-DCI and Call-Paging-DCI).","Then in step 913 the UE determines if the blind decoding is successful.","If yes in step 913, the UE goes go step 914 to determine whether the blind decoding successful with the SI-paging-DCI size or the call-paging DCi size.","If successful with the SI-paging-DCI size, the UE goes to step 915 to obtain SI-Paging information from decoded SI-Paging-DCI.","If successful with the Call-paging-DCI size, the UE goes to step 917 to receive and decode paging information within PDSCH according to obtained scheduling information from decoded Paging-DCI.","Here, the paging information comprises both SI-paging and Call-paging.","If the blind decoding in step 913 is not successful, the UE goes to step 916 to determine as no Paging information at this PO and try the next extended PO.","In another novel aspect, RAR message transmission and content of RAR message are also modified for LC MTC UEs.","For LC-MTC UEs, RAR message is scheduled by RAR-DCI transmitted within MPDCCH.","The transmission of RAR-DCI and RAR message, such as resources and repetition level, depends on the PRACH, wherein the PRACH resources can be partitioned by different CE levels.","The UEs with similar CE requirements are scheduled within a same RAR message to reduce power consumption and resource overhead.","The starting point of RAR message depends on PRACH transmission as well.","Due to the repetition in transmission, the RAR monitoring window is extended in CE mode in one embodiment.","In another embodiment, RAR monitoring window is same as legacy and defined as starting points to monitor RAR-DCI.","Then, the RAR monitoring window doesn't comprise the duration of repeated transmission for RAR-DCI and/or RAR message, and the length of RAR monitoring window is the number of starting points for RAR-DCI monitoring.","For a small payload size, it's more efficient, from the view of resource overhead and power consumption, to transmit the small message by a control channel (like MPDCCH) instead of data channel (like PDSCH), considering different coding schemes for control channel and data channel.","In one embodiment, two RAR modes are introduced.","One is multiple RAR mode, and the other is single RAR mode.","In multiple RAR mode, one or more UEs are multiplexed within one RAR message transmitted by PDSCH, which is scheduled by a multiple RAR-DCI.","In single RAR mode, at least all content within a MAC RAR PDU is carried by a single RAR-DCI, wherein only one UE is carried by the single RAR message.","Further, random access preamble identifier (RAPID) is also transmitted to confirm whether the received DCI is for the UE.","The network can configure only one mode during a period or two modes at the same time.","In a preferred embodiment, only one RAR mode within a cell works through a higher layer configuration.","The DCI format and size are different for single RA mode and multiple RAR mode.","Considering the restriction to LC UEs, some contents within a RAR message can be modified.","One consideration is the size of resource allocation within uplink (UL) grant, which is carried within RAR and used for Msg 3 transmission.","In one embodiment, size of resource allocation varies according to UL system bandwidth to reduce overhead.","In one option, the resource allocation field indicates which narrow band is used and the exact resource allocation within the narrow band.","For LC MTC UEs, UL transmission is limited to one PRB pair to enhance SNR per subcarrier.","Then, the possible size can be {5, 7, 8, 10} bits in one embodiment, wherein only one PRB pair within a narrow band is allocated for transmission.","Another consideration is TPC command within the UL grant.","In a first embodiment, the TPC command is reused as the repetition number for Msg 3 in CE mode.","Since UE can determine its CE level by measurement, the UE knows how to interpret this field.","In a second embodiment, TPC command is not modified, and repetition number for Msg3 is derived from a specific repetition level corresponding to transmitted preamble, without introducing a new field to RAR message.","In a third embodiment, TPC command is also used and additional field is introduced to indicate the repetition number for Msg 3 in CE mode.","Further, the Backoff Indicator (BI) value and transmission can be modified.","In a first embodiment, BI is separated from MAC RAR header and transmitted by RAR-DCI always.","In a second embodiment, BI is transmitted within PDSCH carrying other RAR content, and BI is transmitted within RAR-DCI if there is no UE to be responded by the network.","In a third embodiment, BI is separated from MAC RAR header and configured semi-statically by higher layer, but not transmitted dynamically.","The value of BI can be also extended in CE mode due to a large number of repetitions, which will require more time to transmit a preamble again once there is no RAR for the previous transmitted preamble.","In one embodiment, an extended BI value is obtained by multiplying a coefficient with an indicated normal BI value.","In another embodiment, some new BI values are introduced for LC MTC UEs.","Obviously, RAR-DCI formats are different in single RAR mode and multiple RAR mode.","To facilitate description, RAR-DCI for single RAR is named as single-RAR-DCI, and RAR-DCI for multiple RAR is named as multiple-RAR-DCI.","Then, single-RAR-DCI comprises content within a MAC RAR, RAPID, and optionally BI.","FIG.","10 illustrates an exemplary diagram of the single-RAR-DCI for the single RAR mode in accordance with embodiments of the current invention.","In this example for single-RAR-DCI, it's assumed that TPC command is reused for repetition number.","Then, the RAR-DCI size is identical in both NC mode and CE mode.","The UE can determine it is in CE mode or NC mode by measurement.","The resource allocation (RA) field varies with the UL bandwidth, regardless of CE mode or NC mode.","Accordingly, the size of MAC RAR PDU is {42, 44, 45, 47} bits under different RA sizes, as shown in FIG.","10, and the MAC RAR PDU comprises timing advance (TA), temporary C-RNTI and UL grant.","Note that if an additional field for repetition number is introduced, the size of MAC RAR PDU will increase by 2 bits in one embodiment or 3 bits in another embodiment.","In this example, the single-RAR-DCI also comprises an BI 1001 with four bits, a RAPID 1002 with six bits.","In case of multiple RAR mode, multiple-RAR-DCI is used to schedule a RAR message for one or more UEs.","Similar to Call-paging-DCI, the multiple-RAR-DCI could comprise MCS field and RA field at least.","Further, a repetition number field is introduced to indicate the repetition number for RAR receiving in one embodiment.","In another embodiment, the repetition number for RAR receiving is derived from a basic repetition number corresponding to a specific repetition level and the payload size/coding rate from MCS field.","Considering there may be no MAC RAR transmission, a flag within multiple-RAR-DCI is introduced whether there is MAC RAR PDU transmission.","In one embodiment, BI value is transmitted within the multiple-RAR-DCI when there is no MAC RAR PDU.","In another embodiment, BI value is transmitted with MAC RAR PDU if it exists and carried by PDSCH.","FIG.","11A illustrates an exemplary diagram of the multiple-RAR-DCI for the multiple RAR mode in accordance with embodiments of the current invention.","In this example, the DCI size is the same for both NC mode and CE mode.","The BI is transmitted within multiple-RAR-DCI if there is no MAC RAR PDU, otherwise, it is the first entry of the data packet by PDSCH carrying MAC RAR PDU.","The multiple-RAR-DCI has flag 1101 with one bit, a MCS field 1102 with 4 or 5 bits, a RA field 1103 with the size choosing from {5-bit, 7-bit, 8-bit, 10-bit}, and a 2-bit repetition number field 1104.FIG.","11B illustrates a table for different scenarios to interpret a multiple-RAR-DCI in accordance with embodiments of the current invention.","In this example, if the 1-bit flag is zero, which indicates a scenario without MAC RAR PDU transmission, the multiple-RAR-DCI comprises the flag and the BI.","That means that BI is transmitted within the multiple-RAR-DCI, and no change to the DCI size.","Then, UEs only decode the multiple-RAR-DCI to obtain BI value, without decoding PDSCH.","If the 1-bit flag is set to one, which indicates a scenario with MAC RAR PDU transmission, the BI is within the PDSCH carrying a RAR message.","And the multiple-RAR-DCI under such scenario comprises the one-bit flag, MCS field, RA field and a repetition number in CE mode if DCI format and size are different for NC mode and CE mode.","FIG.","12 shows an exemplary diagram for the first stage of procedure of RAR process for the single RAR or multiple RAR in accordance with embodiments of the current invention.","Note that it's assumed that BI value is transmitted dynamically in the above examples, but not configured by higher layer semi-statically.","At step 1201, the UE determines the CE level based on DL measurement.","At step 1202, the UE determines the time position to monitor the RAR.","At step 1203, the UE determines which RAR mode applies in the current period.","If the single RAR mode is determined at step 1203, the UE blindly decodes the DCI size of the single-RAR-DCI at step 1204.The UE subsequently moves to step 1210 to handle RAR message in the single RAR mode.","If a multiple-RAR-mode is determined at step 1203, the UE moves to step 1205 and blindly decodes DCI size of the multiple-RAR-DCI.","The UE subsequently moves to step 1220 to handle the RAR message in the multiple RAR scenario.","FIG.","13 shows an exemplary diagram for the second stage for the single RAR procedure in accordance with embodiments of the current invention.","At step 1301, the UE determines if blind decoding of the single-RAR-DCI is successful by CRC checking.","If step 1301 determines no, the UE terminates the process, i.e., no control information carrying a MAC RAR PDU is transmitted.","If step 1301 determines yes, the UE moves to step 1301 and checks if there is a RAPID match.","If step 1302 determines no, the UE moves step 1303 and obtains the BI value from the decoded single-RAR-DCI.","If step 1303 determines yes, the UE moves step 1304 and obtains the MAC RAR PDU from the decoded single-RAR-DCI.","FIG.","14 shows an exemplary diagram for the second stage for the multiple RAR procedure in accordance with embodiments of the current invention.","At step 1401, the UE determines whether blind decoding of the multiple-RAR-DCI is successful by CRC checking.","If step 1401 determines no, the UE terminates the process, i.e, the UE determines there is no control information scheduling a MAC RAR PDU from the determined time position.","If step 1401 determines yes, the UE moves to step 1402 and determines if there is any RAR message by decoding the first flag field within the multiple-RAR-DCI.","If step 1402 determines no, the UE moves to step 1403 and obtain the BI value from the decoded multiple-RAR-DCI.","If step 1402 determines yes, the UE moves to step 1404 and decodes the PDSCH.","At step 1405, the UE checks if there is a RAPID match.","If step 1405 determines no, the UE obtains the BI value from the PDSCH at step 1407.If step 1405 determines yes, the UE obtains the RAR content at step 1406.FIG.","15 illustrates an exemplary flow chart for paging scheduling and the DCI format by scheduling the SI-paging and the Call-paging separately in different extended POs in accordance with embodiments of the current invention.","At step 1501, the UE detects a first extended PO for a paging message in a wireless network based on a UE state.","At step 1502, the UE determines the first extended PO is a SI-paging PO or a Call-paging PO.","At step 1503, the UE decodes a SI-paging DCI to obtain a SI-paging message to obtain a change notification of SI if the first extended PO is determined as the SI-paging PO.","At step 1504, the UE decodes a call-paging DCI to obtain scheduling information of a call-paging massage if the first extended PO is determined as a call-paging PO.","FIG.","16 illustrates an exemplary flow chart for paging scheduling and the DCI format by scheduling the SI-paging and the Call-paging at a same time position in accordance with embodiments of the current invention.","At step 1601, the UE detects a first extended PO for a paging message in a wireless network based on a UE state.","At step 1602, the UE performs blind decoding according to SI-paging-DCI format and call-paging-DCI format.","At step 1603, the UE obtains the SI change notification if blind decoding successfully with the SI-paging-DCI format.","At step 1604, the UE obtains a scheduling information of SI-paging message and the call-paging message if decoding successfully with the call-paging-DCI format.","FIG.","17 illustrates an exemplary flow chart for RAR scheduling based on the CE level in accordance with embodiments of the current invention.","At step 1701, the UE determines a coverage enhancement (CE) level based on measurement in a wireless communication network and transmit a preamble from a set of resources corresponding to the determined CE level.","At step 1702, the UE determines a position in a time domain to monitor control information for RAR.","At step 1703, the UE determines whether a RAR mode is a single RAR for a single UE or a multiple RAR for a plurality of UEs.","At step 1704, the UE decodes the RAR based on the CE level and the RAR mode.","Although the present invention has been described in connection with certain specific embodiments for instructional purposes, the present invention is not limited thereto.","Accordingly, various modifications, adaptations, and combinations of various features of the described embodiments can be practiced without departing from the scope of the invention as set forth in the claims."]],"string":"[\n [\n \"Paging and Random Access Response (RAR) Scheduling and DCI Format\",\n \"Methods and apparatus are provided for paging and random access response (RAR) scheduling and downlink control information (DCI) for a user equipment (UE).\",\n \"In one novel aspect, an SI-paging and a call-paging are transmitted separately, and scheduled by SI-Paging-DCI and call-Paging-DCI respectively.\",\n \"In one embodiment, a special PO is introduced for stand-alone SI-Paging scheduled by SI-Paging-DCI, and the special PO is different from the PO for call-Paging.\",\n \"In another novel aspect, SI-Paging is scheduled together with call-paging in the same PDSCH scheduled by call-Paging-DCI.\",\n \"In one embodiment, the SI-paging carries a value tag and a bitmap, wherein the value tag indicates whether any SI updates, and the bitmap indicates which one or more SIs updates.\",\n \"In another embodiment, the SI-Paging carries several valuetags, and the number of valuetag corresponds to the number of SI.\",\n \"The UE compares a current valuetag to a stored valuetag to verify whether a SI changes.\"\n ],\n [\n \"1.A method, comprising: detecting a first extended paging occasion (PO) for a paging message by a low-cost (LC) user equipment (UE) in a wireless network based on a UE state; determining the first extended PO is a SI-paging PO or a call-paging PO; decoding a SI-paging DCI to obtain a SI-paging message to obtain a change notification of SI if the first extended PO is determined as the SI-paging PO; and decoding a call-paging DCI to obtain scheduling information of a call-paging massage if the first extended PO is determined as a call-paging PO.\",\n \"2.The method of claim 1, wherein the paging message is multi-casted to a plurality of UEs, and wherein the paging message carries a group identifier configured for the plurality of UEs.\",\n \"3.The method of claim 2, wherein the group identifier is a logical UE ID.\",\n \"4.The method of claim 2 wherein group identifier is group-specific paging radio network temporary identifier (P-RNTI).\",\n \"5.The method of claim 2, wherein the plurality of UEs is configured with the same group identifier if the plurality of UEs have the same coverage enhancement (CE) level.\",\n \"6.The method of claim 2, wherein the paging message sent repeatedly with a repetition number, and wherein the repetition number is determined by the maximum CE level of the plurality of UEs.\",\n \"7.The method of claim 1, wherein the paging message is control information carrying the SI-Paging message or scheduling information for the call-Paging message.\",\n \"8.The method of claim 1, wherein the SI-paging message comprises a value tag and a bitmap, wherein the value tag indicates whether any SI updates, and the bitmap indicates which one or more SIs update.\",\n \"9.The method of claim 8, wherein a dedicated RNTI is allocated for the SI-paging-DCI.\",\n \"10.The method of claim 1, wherein the call-paging DCI scheduled by a MTC physical downlink control channel (MPDCCH), and the call-paging message is carried by a physical downlink shared channel (PDSCH).\",\n \"11.The method of claim 1, wherein a resource allocation indication is indicated in the call-paging DCI, wherein the resource allocation indication comprising at least one of the following: indicating a frequency location in the narrow band, or indicating the resource allocation within a known narrow band.\",\n \"12.The method of claim 1, wherein an additional extended call-Paging PO is indicated by the call-paging-DCI.\",\n \"13.A method, comprising: detecting a first extended PO for a paging message by a low-cost (LC) user equipment (UE) in a wireless network based on a UE state; perform blind decoding according to SI-paging DCI format and call-paging DCI format; obtaining the SI change notification if blind decoding successfully with the SI-paging-DCI format; obtaining a scheduling information of SI-paging message and the call-paging message if decoding successfully with the call-paging-DCI format.\",\n \"14.The method of claim 13, the paging message is the SI-Paging-DCI or control information scheduling both the SI-Paging and the call-Paging.\",\n \"15.A method, comprising: determining a coverage enhancement (CE) level by a user equipment (UE) based on measurement in a wireless communication network; determining a position in a time domain to monitor control information for random access response (RAR); determining whether a RAR mode is a single RAR for a single UE or a multiple RAR for a plurality of UEs; and decoding the RAR based on the CE level and the RAR mode.\",\n \"16.The method of claim 15, wherein the RAR-DCI has the same size for both enhanced coverage (CE) mode and normal coverage (NC).\",\n \"17.The method of claim 15, wherein a transmit power control (TPC) command field is overloaded with a repetition number if the CE level indicates an enhanced coverage (CE) mode, wherein the repetition number indicates a number of repeated transmissions configured for the CE level to transmit Msg 3.18.The method of claim 15, wherein a backoff indicator (BI) is not transmitted within the RAR or the RAR-DCI, but configured by a higher layer.\",\n \"19.The method of claim 15, wherein a BI is within RAR-DCI if there is no RAR transmitted, otherwise, the BI is within RAR carried by PDSCH.\",\n \"20.The method of claim 15 wherein a BI is transmitted within a RAR-DCI.\"\n ],\n [\n \" BACKGROUND Third generation partnership project (3GPP) and Long Term Evolution (LTE) mobile telecommunication systems provide high data rate, lower latency and improved system performances.\",\n \"Such systems are optimized for regular data communications, wherein there is no need for repeatedly retransmissions.\",\n \"However, in some situations, repeatedly retransmissions are needed.\",\n \"For example, some UEs, in the basements of residential buildings or locations shielded by foil-backed insulation, metalized windows or traditional thick-walled building construction, may experience significantly larger penetration losses on the radio interface than normal LTE devices.\",\n \"More resources/power are needed to support these UEs in the extreme coverage scenario.\",\n \"Repetition has been identified as a common technique to bridge the additional penetration losses than normal LTE devices.\",\n \"In another example, Machine-Type Communication (MTC) is an important revenue stream for operators and has a huge potential from the operator perspective.\",\n \"Lowering the cost of MTC user equipment (UEs)/devices is an important enabler for the implementation of the concept of “Internet of Things” (IOT).\",\n \"The LC-MTC/LC-UE has limited bandwidth.\",\n \"The limited bandwidth and the need to repeatedly transmission require enhancement for paging and RAR procedures.\",\n \"Improvements and enhancements are needed for paging and RAR scheduling for LC-UEs.\"\n ],\n [\n \" SUMMARY Methods and apparatus are provided for paging and RAR scheduling, and corresponding DCI format for low cost UEs.\",\n \"In one novel aspect, an SI-paging (system information-paging) and a call-paging are transmitted separately, and scheduled by SI-Paging-DCI and call-Paging-DCI respectively.\",\n \"In one embodiment, a special PO is introduced for stand-alone SI-Paging scheduled by SI-Paging-DCI, and the special PO is different from the PO for call-Paging.\",\n \"In another novel aspect, SI-Paging is scheduled together with call-paging in the same PDSCH scheduled by call-Paging-DCI.\",\n \"In one embodiment, the SI-paging carries a value tag and a bitmap, wherein the value tag indicates whether any SI updates, and the bitmap indicates which one or more SIs updates.\",\n \"In another embodiment, the SI-Paging carries several valuetags, and the number of valuetag corresponds to the number of SI.\",\n \"The UE compares a current valuetag to a stored valuetag to verify whether a SI changes.\",\n \"In another novel aspect, the RAR scheduling and RAR-DCI format is based on a CE level of the UE.\",\n \"In one embodiment, based on DL measurement, the UE determines a coverage enhancement (CE) level and select a preamble for this CE level in a wireless communication network and determines whether a RAR mode is a single RAR for a single UE or a multiple RAR for a plurality of UE.\",\n \"The UE decodes the RAR based on the CE level of the UE and the RAR mode.\",\n \"In one embodiment, the RAR-DCI has the same size for both coverage enhanced or coverage extension (CE) mode, and normal coverage (NC)mode.\",\n \"In another embodiment, the transmit power control (TPC) command field is overloaded with a repetition number if the CE level indicates a coverage enhanced/extension(CE) mode, wherein the repetition number indicates a number of repetitions for the CE level.\",\n \"Further details and embodiments and methods are described in the detailed description below.\",\n \"This summary does not purport to define the invention.\",\n \"The invention is defined by the claims.\"\n ],\n [\n \"CROSS REFERENCE TO RELATED APPLICATIONS This application is filed under 35 U.S.C.\",\n \"§111(a) and is based on and hereby claims priority under 35 U.S.C.\",\n \"§120 and §365(c) from International Application No.\",\n \"PCT/CN2015/087006, with an international filing date of Aug. 14, 2015.This application is a continuation of International Application No.\",\n \"PCT/CN2015/087006, which is pending as of the filing date of this application, and the United States is a designated state in International Application No.\",\n \"PCT/CN2015/087006.The disclosure of each of the foregoing documents is incorporated herein by reference.\",\n \"TECHNICAL FIELD The disclosed embodiments relate generally to wireless communication, and, more particularly, to paging and random access response (RAR) scheduling and downlink control information (DCI).\",\n \"BACKGROUND Third generation partnership project (3GPP) and Long Term Evolution (LTE) mobile telecommunication systems provide high data rate, lower latency and improved system performances.\",\n \"Such systems are optimized for regular data communications, wherein there is no need for repeatedly retransmissions.\",\n \"However, in some situations, repeatedly retransmissions are needed.\",\n \"For example, some UEs, in the basements of residential buildings or locations shielded by foil-backed insulation, metalized windows or traditional thick-walled building construction, may experience significantly larger penetration losses on the radio interface than normal LTE devices.\",\n \"More resources/power are needed to support these UEs in the extreme coverage scenario.\",\n \"Repetition has been identified as a common technique to bridge the additional penetration losses than normal LTE devices.\",\n \"In another example, Machine-Type Communication (MTC) is an important revenue stream for operators and has a huge potential from the operator perspective.\",\n \"Lowering the cost of MTC user equipment (UEs)/devices is an important enabler for the implementation of the concept of “Internet of Things” (IOT).\",\n \"The LC-MTC/LC-UE has limited bandwidth.\",\n \"The limited bandwidth and the need to repeatedly transmission require enhancement for paging and RAR procedures.\",\n \"Improvements and enhancements are needed for paging and RAR scheduling for LC-UEs.\",\n \"SUMMARY Methods and apparatus are provided for paging and RAR scheduling, and corresponding DCI format for low cost UEs.\",\n \"In one novel aspect, an SI-paging (system information-paging) and a call-paging are transmitted separately, and scheduled by SI-Paging-DCI and call-Paging-DCI respectively.\",\n \"In one embodiment, a special PO is introduced for stand-alone SI-Paging scheduled by SI-Paging-DCI, and the special PO is different from the PO for call-Paging.\",\n \"In another novel aspect, SI-Paging is scheduled together with call-paging in the same PDSCH scheduled by call-Paging-DCI.\",\n \"In one embodiment, the SI-paging carries a value tag and a bitmap, wherein the value tag indicates whether any SI updates, and the bitmap indicates which one or more SIs updates.\",\n \"In another embodiment, the SI-Paging carries several valuetags, and the number of valuetag corresponds to the number of SI.\",\n \"The UE compares a current valuetag to a stored valuetag to verify whether a SI changes.\",\n \"In another novel aspect, the RAR scheduling and RAR-DCI format is based on a CE level of the UE.\",\n \"In one embodiment, based on DL measurement, the UE determines a coverage enhancement (CE) level and select a preamble for this CE level in a wireless communication network and determines whether a RAR mode is a single RAR for a single UE or a multiple RAR for a plurality of UE.\",\n \"The UE decodes the RAR based on the CE level of the UE and the RAR mode.\",\n \"In one embodiment, the RAR-DCI has the same size for both coverage enhanced or coverage extension (CE) mode, and normal coverage (NC)mode.\",\n \"In another embodiment, the transmit power control (TPC) command field is overloaded with a repetition number if the CE level indicates a coverage enhanced/extension(CE) mode, wherein the repetition number indicates a number of repetitions for the CE level.\",\n \"Further details and embodiments and methods are described in the detailed description below.\",\n \"This summary does not purport to define the invention.\",\n \"The invention is defined by the claims.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings, where like numerals indicate like components, illustrate embodiments of the invention.\",\n \"FIG.\",\n \"1 illustrates an exemplary wireless network 100 with enhanced paging and RAR scheduling for LC-UEs in accordance with embodiments of the current invention.\",\n \"FIG.\",\n \"2 illustrates exemplary paging groups to page a group of UEs by the same paging message in accordance with embodiments of the current invention.\",\n \"FIGS.\",\n \"3A and 3B show exemplary diagrams of the SI value tag and bitmap for SI-paging message in accordance with embodiments of the current invention.\",\n \"FIG.\",\n \"4 shows exemplary diagrams of DCI format for call-paging in accordance with embodiments of the current invention.\",\n \"FIG.\",\n \"5 shows an exemplary diagram for a paging procedure with additional Paging Occasion in accordance with the current invention.\",\n \"FIG.\",\n \"6 shows an exemplary diagram for the first stage of procedure when the SI-paging and call-paging are sent separately in accordance with embodiments of the current invention.\",\n \"FIG.\",\n \"7 shows an exemplary diagram for the second stage of SI-paging procedure when the SI-paging and call-paging are sent separately in accordance with embodiments of the current invention.\",\n \"FIG.\",\n \"8 shows an exemplary diagram for the second stage of call-paging procedure when the SI-paging and call-paging are sent separately in accordance with embodiments of the current invention.\",\n \"FIG.\",\n \"9 shows an exemplary flow chart when the SI-paging and call-paging are sent together in accordance with embodiments of the current invention.\",\n \"FIG.\",\n \"10 illustrates an exemplary diagram of the DCI for the single RAR in accordance with embodiments of the current invention.\",\n \"FIG.\",\n \"11A illustrates an exemplary diagram of the DCI for the multiple RARs in accordance with embodiments of the current invention.\",\n \"FIG.\",\n \"11B illustrates a comparison table for different scenarios for a multiple RAR DCI in accordance with embodiments of the current invention.\",\n \"FIG.\",\n \"12 shows an exemplary diagram for the first stage of procedure of RAR process for the single RAR or multiple RAR in accordance with embodiments of the current invention.\",\n \"FIG.\",\n \"13 shows an exemplary diagram for the second stage for the single RAR procedure in accordance with embodiments of the current invention.\",\n \"FIG.\",\n \"14 shows an exemplary diagram for the second stage for the multiple RAR procedure in accordance with embodiments of the current invention.\",\n \"FIG.\",\n \"15 illustrates an exemplary flow chart for paging scheduling and the DCI format by transmitting the SI-paging and the call-paging separately in accordance with embodiments of the current invention.\",\n \"FIG.\",\n \"16 illustrates an exemplary flow chart for paging scheduling and the DCI format by transmitting the SI-paging and the call-paging together in accordance with embodiments of the current invention.\",\n \"FIG.\",\n \"17 illustrates an exemplary flow chart for RAR scheduling based on the CE level in accordance with embodiments of the current invention.\",\n \"DETAILED DESCRIPTION Reference will now be made in detail to some embodiments of the invention, examples of which are illustrated in the accompanying drawings.\",\n \"Currently, the traditional paging scheduling and RAR scheduling are not designed for repeatedly transmissions, wherein paging is to indicate system information (SI) modification and to page idle UE to set up RRC connection, and RAR is a response from eNB for UE transmitted preamble.\",\n \"For example, LC-UE does not support PDCCH, instead, MTC PDCCH (M-PDCCH) is used.\",\n \"Further, UEs still have to blind decode all system information to confirm which system information have modifies, after receiving a paging message for SI update notification.\",\n \"It will introduce much power consumption for LC MTC UEs, which are expected to have a 10-year battery life.\",\n \"To facilitate description, the information within a paging message to indicated system information modification is named as SI-paging, and the information within a paging message to initiate RRC connection setup is named as Call-paging FIG.\",\n \"1 illustrates an exemplary wireless network 100 with enhanced paging and RAR scheduling for LC-UEs in accordance with embodiments of the current invention.\",\n \"Wireless communications system 100 includes one or more wireless networks, and each of the wireless communication network has fixed base infrastructure units, such as 105 and 106.The base units may also be referred to as an access point, an access terminal, a base station, eNB, or by other terminology used in the art.\",\n \"Each of the base stations 105 and 106 serves a geographic area.\",\n \"The geographic area served by wireless communications stations 105 and 106 overlaps in this example.\",\n \"UEs 101 and 102 in the wireless network 100 are served by base station 105.Other UEs, such as UEs 103, 107 and 108, are served by a different base station 106.In one novel aspect, UEs 101, 102, 103, 107 and 108 can be LC-UEs, and the LC-UEs can have different coverage enhancement (CE) level to support coverage extension.\",\n \"In one embodiment, LC-UEs 101, 102, 103, 107 and 108 are real LC-MTC UEs actually.\",\n \"In another embodiment, LC-MTC UEs 101, 102, 103, 107 and 108 are regular UEs that are served/regarded as LC UEs.\",\n \"For example, regular UEs in CE mode can be served as LC UEs.\",\n \"To page a group of UEs with less resource overhead and less power consumption, a single paging message is multi-casted to the group of UEs identified by a group ID in one embodiment.\",\n \"That is there is only one ID to page the group of UEs.\",\n \"In another embodiment, the single paging message for multiple UEs is a function of a group-specific P-RTNI.\",\n \"In this embodiment, the single paging message can be a sequence generated from the P-RNTI, and corresponding UEs determine they are paged if such sequence exists.\",\n \"The group-specific P-RNTI is higher layer configured by broadcast in one design option.\",\n \"For such single paging message without carrying multiple UE specific IDs, the grouping can be (re)configured.\",\n \"In one embodiment, UEs with similar CE levels are grouped together.\",\n \"In another embodiment, UEs with same service/traffic type within a specific area is grouped and identified by a group ID.\",\n \"Then, the group UEs in one single paging message can of the same CE level or different CE level.\",\n \"If the CE level is similar, a repetition number for retransmission is determined based on the common CE level for the paging group in one option.\",\n \"In another option, the paging has a mixed level of CE value.\",\n \"The repetition number is, thereby, the one corresponding to the highest CE level in the paging group.\",\n \"FIG.\",\n \"1 further shows simplified block diagrams of UE 101 and base station 105 in accordance with the current invention.\",\n \"Base station 105 has an antenna array 126 comprising one or more antennas, which transmits and receives radio signals.\",\n \"A RF transceiver module 123, coupled with the antenna, receives RF signals from antenna array 126, converts them to baseband signals and sends them to processor 122.RF transceiver 123 also converts received baseband signals from processor 122, converts them to RF signals, and sends out to antenna array 126.Processor 122 processes the received baseband signals and invokes different functional modules to perform features in base station 105.Memory 121 stores program instructions and data 124 to control the operations of base station 102.Base station 105 also includes a set of control modules, such as a paging and RAR handler 125 that carry out functional tasks to configure, schedule, execute and communicate with the UE 101 for paging and RAR related tasks.\",\n \"UE 101 has an antenna array 135 with single antenna, which transmits and receives radio signals.\",\n \"A RF transceiver module 134, coupled with the antenna, receives RF signals from antenna array 135, converts them to baseband signals and sends them to processor 132.RF transceiver 134 also converts received baseband signals from processor 132, converts them to RF signals, and sends out to antenna 135.Processor 132 processes the received baseband signals and invokes different functional modules to perform features in mobile station 101.Memory 131 stores program instructions and data 136 to control the operations of mobile station 101.UE 101 also includes a set of control modules that carry out functional tasks.\",\n \"A paging handler 191 handles paging monitoring for both SI-paging and Call-paging.\",\n \"A RAR handler 192 handles RAR procedure based on the CE level for both the single RAR and multiple RAR.\",\n \"In one novel aspect, a paging message is multi-casted to a plurality of UEs.\",\n \"The group of UEs can be paged by one same group ID with a very small payload size.\",\n \"The power consumption and resource efficiency are improved, especially for LC-UEs with repeatedly transmissions.\",\n \"FIG.\",\n \"2 illustrates exemplary paging groups to page different group of UEs by the same single paging message in accordance with embodiments of the current invention.\",\n \"A base station 209 covers a plurality of UEs with different CE levels.\",\n \"FIG.\",\n \"2 shows four exemplary diagrams of different grouping for the paging message according to different rules.\",\n \"In one embodiment, UEs with the same service type but different CE levels are grouped together, and configured by a same group ID.\",\n \"As shown, paging group 210 includes four UEs, UE 211, UE 212, UE 213, and UE 214 with CE levels being CE level-1, CE level-3, CE level-4 and CE level-1, respectively.\",\n \"All the UEs in the same paging group have the same group ID-1.A paging message 201 is multi-casted with the group ID-1.The one paging message 201 covers the four UEs in the same paging group 210.In one embodiment, repeatedly transmissions are required for UE in CE mode.\",\n \"In one option, the number of repetition is based on the higher CE level.\",\n \"In this example, each UE in group-1, UEs 211, 212, 213 and 214, receives repetition transmission with a repetition number corresponding to a CE level-4, which is the highest CE level in group-1.Such grouping can preconfigured by the network or by higher layer signaling.\",\n \"In another embodiment, the UEs with the same CE-level are grouped together.\",\n \"A paging group 220, including UE 221, 222, and 223 are grouped together with the same paging group ID-2.Each UE in paging group 220 has the same CE level, i.e., CE level-1.A paging message 202 is multi-casted to all UEs in paging group 220 with the same repetition number based the common CE level (CE level-1).\",\n \"In other embodiments, a group-specific P-RNTI is used to identify a paging group.\",\n \"A paging group 230 includes UEs 231, 232, and 233, with CE level-1, CE level-5 and CE level-2, respectively.\",\n \"A paging message 203 is multi-casted to each UE in paging group 230 with a group-specific P-RNTI, P-RNTI-1.The repetition number is set to be corresponding to the highest CE level of the group, which is CE level-5.In yet another embodiment, the UEs with the same CE level are grouped together by another group-specific P-RNTI, P-RNTI-2.As shown, a paging group 240 includes UEs 241 and 242, each with the same CE level-2.A paging message 204 is multi-casted to each UE in paging group 240 with P-RNTI-1, wherein the repetition number is set to be correspondence to CE level-1, while a paging message 203 is transmitted to each UE within paging group 230 with P-RNTI-2, wherein the repetition number is set to be corresponding to CE level-5, the highest CE level within paging group 230.To reduce UE power consumption, it's expected that SI-paging can indicate which system information (including M-MIB (MTC MIB) and M-SIB (MIC SIB) information for LC MTC UEs) will update.\",\n \"In one case, that SI-paging is always transmitted regardless whether there are SI changes in one embodiment.\",\n \"In another embodiment, SI-paging is transmitted only when there will be some update to some system information.\",\n \"In one novel aspect, the SI-paging comprises a bitmap and a value tag.\",\n \"The bitmap indicates which system information changes and the value tag indicates whether there is any M-SI (MTC-SI) updates.\",\n \"In this novel aspect, the length of the bitmap is equal to the number of M-SI messages for MTC UEs in one embodiment.\",\n \"Here, change of M-MIB is not indicated.\",\n \"In another embodiment, the length of the bitmap is equal to the number of SI message for MTC UEs plus 1 to indicate the update of both M-MIB and M-SI.\",\n \"The value range of value tag can be denoted as an integer with Y bits, while candidate value for Y is {4, 5}.\",\n \"In another novel aspect, the SI-Paging comprises several value tags and each value tag indicates whether corresponding system information will update.\",\n \"Here, the total value tag number is equal to the bitmap length in the on novel aspect, and the value range of each value tag equals to the value tag in the one novel aspect.\",\n \"FIG.\",\n \"3A shows an exemplary diagram of the SI value tag and bitmap for SI-paging message in accordance with embodiments of the current invention.\",\n \"In one embodiment, within SI-paging, there is an X-bit value tag 301 and Y-bit bitmap 302.In one embodiment, value tag 301 has five bits and indicates any changes to some system information.\",\n \"The UE compares the received value tag with the value tag it receives last time.\",\n \"If value tag 301 changes, it indicates there exists update to system information.\",\n \"The UE, subsequently, checks the Y-bit bitmap 302 to determine which M-SI or M-MIB will update.\",\n \"Bitmap 302 indicates one M-SI or M-MIB update by set the corresponding bit in bitmap 302, for example, to 1.FIG.\",\n \"3B shows an exemplary diagram of the SI value tag and bitmap for SI-paging message in accordance with embodiments of the current invention.\",\n \"In this figure, there are Y value tags {303, 304, 305, 306} within the SI-Paging.\",\n \"In this example, M-MIB change is indicated by a value tag 303 within SI-paging.\",\n \"Further, there are 3 M-SI messages for MTC UEs, and each M-SI change notification is denoted as value tag 304, 305, 306, respectively.\",\n \"If the value of any value tag changes, the UE can determine that the corresponding system information changes or will change.\",\n \"For LC MTC UEs, the format of DCI for scheduling a paging message is different from legacy DCI format.\",\n \"One consideration is Resource Allocation (RA) field.\",\n \"Due to bandwidth reduction, resources are restricted to a limited size, e.g., 6 PRB pairs (1.4 MHz).\",\n \"Then, a RA filed should indicate which narrow band is used for paging message transmission, or how many resources are allocated within a narrow band.\",\n \"In a first embodiment, only a narrow band location for the paging message is indicated within the RA field, wherein it's assumed that all resources within the indicated narrow band are used for transmission.\",\n \"In a second embodiment, resources within a known narrow band are indicated by the RA field, wherein the known narrow band is (re)configured by higher layer, or predefined, or derived from a rule.\",\n \"In a third embodiment, the RA filed indicates a narrow band location and resource allocation within the indicated narrow band.\",\n \"The length of RA field depends on the whole channel bandwidth.\",\n \"Taking 20 MHz bandwidth as an example, the RA filed size can be 4 bits under the first embodiment, and 5 bits under the second embodiment considering 1.4 MHz limitation, and 9 bits in the third embodiment.\",\n \"Further, the modulation order may be restricted for MTC UEs with payload size limitation and cost reduction.\",\n \"For example, 16 QAM can be supported in normal CE mode, and only QPSK is applied in the CE mode.\",\n \"Then, Modulation And Coding Scheme (MCS) field can be 4 bits or 5 bits.\",\n \"Also, the payload size can be larger if there are multiple UEs to be paged within one paging message.\",\n \"The payload size indicated by the MCS field is the exact size of the paging message.\",\n \"In another embodiment, the payload size for the paging message is the indicated payload size by the MCS field plus the payload size of SI-paging.\",\n \"Thirdly, a field for repetition number indication is also needed in the CE mode.\",\n \"In one embodiment, a repetition number is explicitly given by the repetition number field.\",\n \"It can be interpreted as no coverage extension in case the indicated repetition number is 1.In another embodiment, an coefficient is given within the repetition number field, and the UE derives the exact repetition number by multiplexing the coefficient with a basic repetition number.\",\n \"Here, the basic repetition number is broadcast or predefined.\",\n \"Then, a DCI format for LC MTC UEs to receive paging message may comprise modulation coding scheme (MCS) field, RA field, and repetition indication field at least.\",\n \"Considering blocking rate or in case of massive number of UE, one more field for dynamic extended PO allocation can be comprised to indicate an additional extended PO dynamically.\",\n \"For example, a value 1 for this single bit can be interpreted that there is an additional extended PO.\",\n \"To facilitate description, a current extended PO to receive/decode control information is named as a first extended PO, and the indicated additional extended PO from the decoded DCI at the first extended PO can be also named as a second extended PO.\",\n \"Then, if one UE finds it is not paged within current paging message, which is scheduled by the control information at the first extended PO, the UE can try to decode another DCI for paging message at the indicated second extended PO.\",\n \"In one embodiment, the additional PO indication always exist.\",\n \"Then, UE always blind decodes one DCI size, i.e.\",\n \"the Call-paging DCI size.\",\n \"In another embodiment, the additional extended PO indication is optional.\",\n \"Then, UEs should blind decode two different DCI sizes.\",\n \"The position of the indicated additional extended PO can be determined by adding a basic time distance predefined according to different CE levels to the determined first extended PO.\",\n \"FIG.\",\n \"4 shows exemplary diagrams of DCI format to schedule paging message to LC MTC UEs in accordance with embodiments of the current invention.\",\n \"A paging DCI 400 includes a MCS field 401, a RA field 402, a repetition number field 403, and an additional extended PO field 404.MCS field 401 can be 4 bits or 5 bits depending on a UE number within a paging message and the CE level.\",\n \"In one embodiment, a 4-bit MCS field is for QPSK; while a 5-bit MCS field is for 16 QPSK.\",\n \"RA field 402 has 4 bits, 5 bits or 9 bits under different embodiments.\",\n \"Repetition number field 403 can be a 2-bit field or a 3-bit field.\",\n \"The 1-bit additional PO field 404 indicates whether there is another available extended PO for a paging message following current determined extended PO.\",\n \"FIG.\",\n \"5 shows an exemplary diagram for a paging procedure with additional extended PO in accordance with the current invention.\",\n \"At step 501, the UE decodes a DCI for paging messages at an extended PO 521.The DCI in step 501 indicates one additional extended PO.\",\n \"At step 502, the UE receives a paging message according to the DCI decoded in step 501.At step 510, based on the additional extended PO indicated in step 501, the UE moves to decode another DCI at the additional extended PO 522 (step 503).\",\n \"At step 503, the UE decodes the second DCI for another paging monitoring.\",\n \"Based on the decoded DCI at step 503, the UE decodes another paging message at step 504.In legacy system, paging occasion (PO) is a subframe carrying both the control information and the paging message.\",\n \"Considering the characteristics of LC MTC UEs, UEs may decode control information scheduling a paging message in one subframe, and receive the corresponding paging message in another subframe, since the control information and the paging message may locate in different narrow bands.\",\n \"Further, in case of CE mode with repetitions, UEs should also decode the control information first within multiple subframes, before decoding the corresponding paging message.\",\n \"Therefore, the UE should determine a starting point to decode control information when monitoring the paging message.\",\n \"In this invention, an extended PO is introduced for paging message monitoring for LC MTC UEs, wherein the extended PO is a starting point or a position in time domain to decode control information scheduling a paging message comprising SI-paging and Call-paging.\",\n \"Call-paging is to initiate RRC connection, so it is only monitored by idle UEs without RRC connection.\",\n \"SI-paging is for all UEs to verify there is system information update.\",\n \"In this invention, connected UEs, i.e., UEs with RRC connection, determine to receive and decode corresponding system information, after receiving the SI-paging, in one embodiment.\",\n \"In another embodiment, updated information elements (IEs) within corresponding system information is transmitted to UEs specifically by network, and the received information will apply at next modification period.\",\n \"Note that not the whole of one or more M-SI messages are transmitted, but only the updated part of each M-SI message is transmitted.\",\n \"In one embodiment, the SI-paging and the Call-paging are transmitted and received separately in different time positions.\",\n \"Specifically, the SI-paging is carried by a SI-paging DCI within MTC PDCCH (MPDCCH) transmitted at a dedicated extended PO for SI-paging (i.e., SI-paging-PO).\",\n \"The Call-paging is carried by the PDSCH scheduled by a Call-paging-DCI within MPDCCH which is transmitted from another extended PO for Call-paging (i.e., Call-paging-PO).\",\n \"In this novel aspect, the UE checks whether there is SI updates by detecting the SI-paging, when the UE is in the connected state.\",\n \"When the UE is the IDLE mode, the UE monitors Call-paging or SI-paging at each different extended PO.\",\n \"In another embodiment, the SI-paging and the Call-paging are scheduled together at a same extended PO.\",\n \"Specifically, The SI-paging is transmitted by a SI-paging-DCIif no Call-paging is transmitted, and the SI-paging is carried by the PDSCH scheduled by the Call-paging-DCI, if there is call-paging transmission.\",\n \"In this novel aspect, when the UE is in the connected state, the updated IEs within corresponding system information message are transmitted to UE specifically by the eNB scheduling.\",\n \"When the UE is in the IDLE mode, the UE monitors both call-paging and SI-paging at each extended PO.\",\n \"FIG.\",\n \"6 shows an exemplary diagram for the first stage of procedure when the SI-paging and call-paging are scheduled separately at different extended POs in accordance with embodiments of the current invention.\",\n \"At step 601, the UE determines a time position, e.g., an extended PO, to monitor the paging information.\",\n \"At step 602, the UE determines whether it is in the IDLE state.\",\n \"If step 602 determines no, the UE moves to step 604 and blindly decodes the SI-paging DCI with the SI-paging DCI size within time-frequency resources, since connected UE only monitors SI-paging.\",\n \"The UE subsequently continues to step 610 to deal with the SI-paging message.\",\n \"If step 602 determines yes, the UE moves step 603.At step 603, the UE determines if the determined extended PO is used for SI-paging.\",\n \"If the step 603 determines yes, the UE moves to step 604 and continues.\",\n \"If the step 603 determines no, i.e., the determined extended PO is used for Call-paging, which means the current extended PO is a Call-paging PO, the UE blindly decodes the DCI with Call-paging DCI size within a determined set of time-frequency resources to obtain a location for Call-paging (step 605).\",\n \"The UE subsequently continues to step 620 to deal with the Call-paging message.\",\n \"FIG.\",\n \"7 shows an exemplary diagram for the second stage of SI-paging procedure when the SI-paging and Call-paging are scheduled separately at different extended POs in accordance with embodiments of the current invention.\",\n \"At step 701, followed by step 610 of blindly decoding SI-paging-DCI, the UE determines if the blind decoding is successful by checking the CRC.\",\n \"If step 701 determines no, the UE moves to step 703 and waits for the next SI-paging PO, wherein assuming SI-Paging is not transmitted at each possible SI-paging PO.\",\n \"If step 701 determines yes the UE moves step 702 and obtains change notification of system information.\",\n \"Based on step 702, the UE, at step 704, decodes and updates corresponding M-MIB or M-SI message at proper time positions.\",\n \"FIG.\",\n \"8 shows an exemplary diagram for the second stage of Call-paging procedure when the SI-paging and call-paging are scheduled separately in different extended POs in accordance with embodiments of the current invention.\",\n \"At step 801, followed by step 620 of blindly decoding the Call-paging-DCI, the UE determines if the decoding is successful by checking the CRC.\",\n \"If step 701 determines no, the UE moves to step 806 and waits to try the next Call-paging PO.\",\n \"If step 801 determines yes the UE moves to step 802.At step 802, the UE decodes the PDSCH according to the decoded DCI.\",\n \"The UE, subsequently, checks whether it has been paged in step 803.If step 803 determines yes, the UE moves to step 804, and obtains paging information and prepares for the RRC connection setup.\",\n \"If step 803 determines no, there are two options for the next step.\",\n \"In the first option, there is no additional extended PO for the UE, the UE will stop the paging process and moves to wait for the next extended PO.\",\n \"In the second option, the UE moves to step 810 and checks if there is additional extended PO indicated by the decoded Call-paging-DCI.\",\n \"If step 810 determines no, the UE will stop the paging process and moves to wait for the next extended PO.\",\n \"If step 810 determines yes, the UE will go back to step 605 to blindly decode for the Call-paging-DCI at the additional extended PO.\",\n \"FIG.\",\n \"9 shows an exemplary flow chart when the SI-paging and call-paging are scheduled together at a same extended PO in accordance with embodiments of the current invention.\",\n \"First in step 911, the UE determines a time position, i.e.\",\n \"PO to monitor paging information.\",\n \"Then in step 912, the UE determines the frequency location to receive Paging DCI and blind decode two different DCI sizes (SI-Paging-DCI and Call-Paging-DCI).\",\n \"Then in step 913 the UE determines if the blind decoding is successful.\",\n \"If yes in step 913, the UE goes go step 914 to determine whether the blind decoding successful with the SI-paging-DCI size or the call-paging DCi size.\",\n \"If successful with the SI-paging-DCI size, the UE goes to step 915 to obtain SI-Paging information from decoded SI-Paging-DCI.\",\n \"If successful with the Call-paging-DCI size, the UE goes to step 917 to receive and decode paging information within PDSCH according to obtained scheduling information from decoded Paging-DCI.\",\n \"Here, the paging information comprises both SI-paging and Call-paging.\",\n \"If the blind decoding in step 913 is not successful, the UE goes to step 916 to determine as no Paging information at this PO and try the next extended PO.\",\n \"In another novel aspect, RAR message transmission and content of RAR message are also modified for LC MTC UEs.\",\n \"For LC-MTC UEs, RAR message is scheduled by RAR-DCI transmitted within MPDCCH.\",\n \"The transmission of RAR-DCI and RAR message, such as resources and repetition level, depends on the PRACH, wherein the PRACH resources can be partitioned by different CE levels.\",\n \"The UEs with similar CE requirements are scheduled within a same RAR message to reduce power consumption and resource overhead.\",\n \"The starting point of RAR message depends on PRACH transmission as well.\",\n \"Due to the repetition in transmission, the RAR monitoring window is extended in CE mode in one embodiment.\",\n \"In another embodiment, RAR monitoring window is same as legacy and defined as starting points to monitor RAR-DCI.\",\n \"Then, the RAR monitoring window doesn't comprise the duration of repeated transmission for RAR-DCI and/or RAR message, and the length of RAR monitoring window is the number of starting points for RAR-DCI monitoring.\",\n \"For a small payload size, it's more efficient, from the view of resource overhead and power consumption, to transmit the small message by a control channel (like MPDCCH) instead of data channel (like PDSCH), considering different coding schemes for control channel and data channel.\",\n \"In one embodiment, two RAR modes are introduced.\",\n \"One is multiple RAR mode, and the other is single RAR mode.\",\n \"In multiple RAR mode, one or more UEs are multiplexed within one RAR message transmitted by PDSCH, which is scheduled by a multiple RAR-DCI.\",\n \"In single RAR mode, at least all content within a MAC RAR PDU is carried by a single RAR-DCI, wherein only one UE is carried by the single RAR message.\",\n \"Further, random access preamble identifier (RAPID) is also transmitted to confirm whether the received DCI is for the UE.\",\n \"The network can configure only one mode during a period or two modes at the same time.\",\n \"In a preferred embodiment, only one RAR mode within a cell works through a higher layer configuration.\",\n \"The DCI format and size are different for single RA mode and multiple RAR mode.\",\n \"Considering the restriction to LC UEs, some contents within a RAR message can be modified.\",\n \"One consideration is the size of resource allocation within uplink (UL) grant, which is carried within RAR and used for Msg 3 transmission.\",\n \"In one embodiment, size of resource allocation varies according to UL system bandwidth to reduce overhead.\",\n \"In one option, the resource allocation field indicates which narrow band is used and the exact resource allocation within the narrow band.\",\n \"For LC MTC UEs, UL transmission is limited to one PRB pair to enhance SNR per subcarrier.\",\n \"Then, the possible size can be {5, 7, 8, 10} bits in one embodiment, wherein only one PRB pair within a narrow band is allocated for transmission.\",\n \"Another consideration is TPC command within the UL grant.\",\n \"In a first embodiment, the TPC command is reused as the repetition number for Msg 3 in CE mode.\",\n \"Since UE can determine its CE level by measurement, the UE knows how to interpret this field.\",\n \"In a second embodiment, TPC command is not modified, and repetition number for Msg3 is derived from a specific repetition level corresponding to transmitted preamble, without introducing a new field to RAR message.\",\n \"In a third embodiment, TPC command is also used and additional field is introduced to indicate the repetition number for Msg 3 in CE mode.\",\n \"Further, the Backoff Indicator (BI) value and transmission can be modified.\",\n \"In a first embodiment, BI is separated from MAC RAR header and transmitted by RAR-DCI always.\",\n \"In a second embodiment, BI is transmitted within PDSCH carrying other RAR content, and BI is transmitted within RAR-DCI if there is no UE to be responded by the network.\",\n \"In a third embodiment, BI is separated from MAC RAR header and configured semi-statically by higher layer, but not transmitted dynamically.\",\n \"The value of BI can be also extended in CE mode due to a large number of repetitions, which will require more time to transmit a preamble again once there is no RAR for the previous transmitted preamble.\",\n \"In one embodiment, an extended BI value is obtained by multiplying a coefficient with an indicated normal BI value.\",\n \"In another embodiment, some new BI values are introduced for LC MTC UEs.\",\n \"Obviously, RAR-DCI formats are different in single RAR mode and multiple RAR mode.\",\n \"To facilitate description, RAR-DCI for single RAR is named as single-RAR-DCI, and RAR-DCI for multiple RAR is named as multiple-RAR-DCI.\",\n \"Then, single-RAR-DCI comprises content within a MAC RAR, RAPID, and optionally BI.\",\n \"FIG.\",\n \"10 illustrates an exemplary diagram of the single-RAR-DCI for the single RAR mode in accordance with embodiments of the current invention.\",\n \"In this example for single-RAR-DCI, it's assumed that TPC command is reused for repetition number.\",\n \"Then, the RAR-DCI size is identical in both NC mode and CE mode.\",\n \"The UE can determine it is in CE mode or NC mode by measurement.\",\n \"The resource allocation (RA) field varies with the UL bandwidth, regardless of CE mode or NC mode.\",\n \"Accordingly, the size of MAC RAR PDU is {42, 44, 45, 47} bits under different RA sizes, as shown in FIG.\",\n \"10, and the MAC RAR PDU comprises timing advance (TA), temporary C-RNTI and UL grant.\",\n \"Note that if an additional field for repetition number is introduced, the size of MAC RAR PDU will increase by 2 bits in one embodiment or 3 bits in another embodiment.\",\n \"In this example, the single-RAR-DCI also comprises an BI 1001 with four bits, a RAPID 1002 with six bits.\",\n \"In case of multiple RAR mode, multiple-RAR-DCI is used to schedule a RAR message for one or more UEs.\",\n \"Similar to Call-paging-DCI, the multiple-RAR-DCI could comprise MCS field and RA field at least.\",\n \"Further, a repetition number field is introduced to indicate the repetition number for RAR receiving in one embodiment.\",\n \"In another embodiment, the repetition number for RAR receiving is derived from a basic repetition number corresponding to a specific repetition level and the payload size/coding rate from MCS field.\",\n \"Considering there may be no MAC RAR transmission, a flag within multiple-RAR-DCI is introduced whether there is MAC RAR PDU transmission.\",\n \"In one embodiment, BI value is transmitted within the multiple-RAR-DCI when there is no MAC RAR PDU.\",\n \"In another embodiment, BI value is transmitted with MAC RAR PDU if it exists and carried by PDSCH.\",\n \"FIG.\",\n \"11A illustrates an exemplary diagram of the multiple-RAR-DCI for the multiple RAR mode in accordance with embodiments of the current invention.\",\n \"In this example, the DCI size is the same for both NC mode and CE mode.\",\n \"The BI is transmitted within multiple-RAR-DCI if there is no MAC RAR PDU, otherwise, it is the first entry of the data packet by PDSCH carrying MAC RAR PDU.\",\n \"The multiple-RAR-DCI has flag 1101 with one bit, a MCS field 1102 with 4 or 5 bits, a RA field 1103 with the size choosing from {5-bit, 7-bit, 8-bit, 10-bit}, and a 2-bit repetition number field 1104.FIG.\",\n \"11B illustrates a table for different scenarios to interpret a multiple-RAR-DCI in accordance with embodiments of the current invention.\",\n \"In this example, if the 1-bit flag is zero, which indicates a scenario without MAC RAR PDU transmission, the multiple-RAR-DCI comprises the flag and the BI.\",\n \"That means that BI is transmitted within the multiple-RAR-DCI, and no change to the DCI size.\",\n \"Then, UEs only decode the multiple-RAR-DCI to obtain BI value, without decoding PDSCH.\",\n \"If the 1-bit flag is set to one, which indicates a scenario with MAC RAR PDU transmission, the BI is within the PDSCH carrying a RAR message.\",\n \"And the multiple-RAR-DCI under such scenario comprises the one-bit flag, MCS field, RA field and a repetition number in CE mode if DCI format and size are different for NC mode and CE mode.\",\n \"FIG.\",\n \"12 shows an exemplary diagram for the first stage of procedure of RAR process for the single RAR or multiple RAR in accordance with embodiments of the current invention.\",\n \"Note that it's assumed that BI value is transmitted dynamically in the above examples, but not configured by higher layer semi-statically.\",\n \"At step 1201, the UE determines the CE level based on DL measurement.\",\n \"At step 1202, the UE determines the time position to monitor the RAR.\",\n \"At step 1203, the UE determines which RAR mode applies in the current period.\",\n \"If the single RAR mode is determined at step 1203, the UE blindly decodes the DCI size of the single-RAR-DCI at step 1204.The UE subsequently moves to step 1210 to handle RAR message in the single RAR mode.\",\n \"If a multiple-RAR-mode is determined at step 1203, the UE moves to step 1205 and blindly decodes DCI size of the multiple-RAR-DCI.\",\n \"The UE subsequently moves to step 1220 to handle the RAR message in the multiple RAR scenario.\",\n \"FIG.\",\n \"13 shows an exemplary diagram for the second stage for the single RAR procedure in accordance with embodiments of the current invention.\",\n \"At step 1301, the UE determines if blind decoding of the single-RAR-DCI is successful by CRC checking.\",\n \"If step 1301 determines no, the UE terminates the process, i.e., no control information carrying a MAC RAR PDU is transmitted.\",\n \"If step 1301 determines yes, the UE moves to step 1301 and checks if there is a RAPID match.\",\n \"If step 1302 determines no, the UE moves step 1303 and obtains the BI value from the decoded single-RAR-DCI.\",\n \"If step 1303 determines yes, the UE moves step 1304 and obtains the MAC RAR PDU from the decoded single-RAR-DCI.\",\n \"FIG.\",\n \"14 shows an exemplary diagram for the second stage for the multiple RAR procedure in accordance with embodiments of the current invention.\",\n \"At step 1401, the UE determines whether blind decoding of the multiple-RAR-DCI is successful by CRC checking.\",\n \"If step 1401 determines no, the UE terminates the process, i.e, the UE determines there is no control information scheduling a MAC RAR PDU from the determined time position.\",\n \"If step 1401 determines yes, the UE moves to step 1402 and determines if there is any RAR message by decoding the first flag field within the multiple-RAR-DCI.\",\n \"If step 1402 determines no, the UE moves to step 1403 and obtain the BI value from the decoded multiple-RAR-DCI.\",\n \"If step 1402 determines yes, the UE moves to step 1404 and decodes the PDSCH.\",\n \"At step 1405, the UE checks if there is a RAPID match.\",\n \"If step 1405 determines no, the UE obtains the BI value from the PDSCH at step 1407.If step 1405 determines yes, the UE obtains the RAR content at step 1406.FIG.\",\n \"15 illustrates an exemplary flow chart for paging scheduling and the DCI format by scheduling the SI-paging and the Call-paging separately in different extended POs in accordance with embodiments of the current invention.\",\n \"At step 1501, the UE detects a first extended PO for a paging message in a wireless network based on a UE state.\",\n \"At step 1502, the UE determines the first extended PO is a SI-paging PO or a Call-paging PO.\",\n \"At step 1503, the UE decodes a SI-paging DCI to obtain a SI-paging message to obtain a change notification of SI if the first extended PO is determined as the SI-paging PO.\",\n \"At step 1504, the UE decodes a call-paging DCI to obtain scheduling information of a call-paging massage if the first extended PO is determined as a call-paging PO.\",\n \"FIG.\",\n \"16 illustrates an exemplary flow chart for paging scheduling and the DCI format by scheduling the SI-paging and the Call-paging at a same time position in accordance with embodiments of the current invention.\",\n \"At step 1601, the UE detects a first extended PO for a paging message in a wireless network based on a UE state.\",\n \"At step 1602, the UE performs blind decoding according to SI-paging-DCI format and call-paging-DCI format.\",\n \"At step 1603, the UE obtains the SI change notification if blind decoding successfully with the SI-paging-DCI format.\",\n \"At step 1604, the UE obtains a scheduling information of SI-paging message and the call-paging message if decoding successfully with the call-paging-DCI format.\",\n \"FIG.\",\n \"17 illustrates an exemplary flow chart for RAR scheduling based on the CE level in accordance with embodiments of the current invention.\",\n \"At step 1701, the UE determines a coverage enhancement (CE) level based on measurement in a wireless communication network and transmit a preamble from a set of resources corresponding to the determined CE level.\",\n \"At step 1702, the UE determines a position in a time domain to monitor control information for RAR.\",\n \"At step 1703, the UE determines whether a RAR mode is a single RAR for a single UE or a multiple RAR for a plurality of UEs.\",\n \"At step 1704, the UE decodes the RAR based on the CE level and the RAR mode.\",\n \"Although the present invention has been described in connection with certain specific embodiments for instructional purposes, the present invention is not limited thereto.\",\n \"Accordingly, various modifications, adaptations, and combinations of various features of the described embodiments can be practiced without departing from the scope of the invention as set forth in the claims.\"\n ]\n]"},"source":{"kind":"string","value":"Patent_15871983"}}},{"rowIdx":4493972,"cells":{"text":{"kind":"list like","value":[["METHOD FOR PRODUCTION OF ACTIVATED CARBON FABRICS FROM COTTON","An improved method of producing activated carbon fabrics from cotton fabrics involves washing a piece of cotton fabric with a detergent before soaking the washed piece of cotton fabric in an acidic chemical such as phosphoric acid for a specific amount of time, and then drying the soaked piece of cotton fabric in an oven.","After the fabric has been dried, it is heated in a furnace which is fed with a flow of nitrogen gas as the temperature of the furnace is gradually increased to a pre-determined temperature and kept at the pre-determined temperature for an extended amount of time, before allowing the temperature to gradually return back to room temperature.","After being removed from the furnace and being washed with distilled water to remove any remnants of phosphoric acid, the resulting product is an activated carbon fabric."],["1.A method of producing an activated carbon fabric, comprising: preparing a piece of cotton fabric; washing the prepared piece of cotton fabric; treating the washed piece of cotton fabric with an acidic chemical; drying the treated piece of cotton fabric with a first heating source; when the treated piece of cotton fabric has dried, heating the treated piece of cotton fabric with a second heating source while feeding the second heating source with nitrogen gas; removing the heated piece of cotton fabric from the second heating source; and rinsing the heated piece of cotton fabric.","2.The method of producing an activated carbon fabric of claim 1, wherein washing the piece of cotton fabric comprises washing the piece of cotton fabric with a non-ionic detergent and rinsing the piece of cotton fabric with distilled water.","3.The method of producing an activated carbon fabric of claim 1, wherein the acidic chemical comprises phosphoric acid.","4.The method of producing an activated carbon fabric of claim 3, wherein the acidic chemical comprises phosphoric acid comprises an 85% aqueous solution.","5.The method of producing an activated carbon fabric of claim 1, wherein treating the washed piece of cotton fabric with an acidic chemical comprises soaking the washed piece of cotton fabric in an acidic chemical for an extended period of time.","6.The method of producing an activated carbon fabric of claim 5, wherein the extended period of time comprises 24 hours.","7.The method of producing an activated carbon fabric of claim 1, wherein the first heating source is an oven.","8.The method of producing an activated carbon fabric of claim 7, wherein the treated piece of cotton fabric is dried in the oven at a temperature of between 105 to 110 degrees Celsius.","9.The method of producing an activated carbon fabric of claim 7, wherein the treated piece of cotton fabric is dried in the oven for one hour.","10.The method of producing an activated carbon fabric of claim 1, wherein the second heating source is a furnace.","11.The method of producing an activated carbon fabric of claim 10, wherein the furnace is an electric furnace.","12.The method of producing an activated carbon fabric of claim 10, wherein heating the first the treated piece of cotton fabric in the furnace comprises: feeding the furnace with the flow of the nitrogen gas while a temperature of the furnace is increased at a pre-determined rate to a desired temperature; keeping the treated piece of cotton fabric at the furnace at the desired temperature for a specific amount of time; and turning off the furnace and letting the treated piece of cotton fabric cool down in the furnace until a temperature of the treated piece of cotton fabric returns to room temperature.","13.The method of producing an activated carbon fabric of claim 12, wherein the desired temperature is 500 degrees Celsius.","14.The method of producing an activated carbon fabric of claim 12, wherein the specific amount of time is 30 minutes.","15.The method of producing an activated carbon fabric of claim 1, wherein rinsing the treated piece of cotton fabric comprises rinsing the fabric with distilled water.","16.The method of producing an activated carbon fabric of claim 15, wherein the distilled water is at a boiling temperature.","17.The method of producing an activated carbon fabric of claim 1, further comprising drying the treated piece of cotton fabric after rinsing it.","18.The method of producing an activated carbon fabric of claim 17, wherein drying the treated piece of cotton fabric after rinsing it occurs at an oven."],[" BACKGROUND In recent years, the use of activated carbon has been increased in a number of industries, as it has been recognized as a highly effective absorbent material for removing gases, vapors, dyes and other organic compounds from vapor and liquid mediums.","As a result, activated carbon is often used in filters and masks for removing unwanted chemicals.","A wide range of carbonaceous precursors, such as coal, wood, byproducts and agricultural byproducts can be used to produce activated carbon.","The activated carbon produced from these materials, however, is in powder and/or granular form.","This limits the application of the produced activated carbon, as the form most often desired for use of activated carbon is a cloth or fabric.","To achieve this form of activated carbon, the powder and granular activated carbon is often converted to a fibrous or textile material by mixing it with a binding agent.","The process of conversion, however, is often time and labor consuming.","Moreover, because of the use of the binding agent, the resulting product often has a reduced active surface area, thereby decreasing the protentional filtering capabilities of the resulting product.","Therefore, a need exists for providing an improved method of producing activated carbon fabrics that is easy to use, reduces time and expense, and provides a higher quality product."],[" SUMMARY A method for producing an activated carbon fabric is provided.","In one implementation, the method includes preparing a piece of cotton fabric, washing the prepared piece of cotton fabric, treating the washed piece of cotton fabric with an acidic chemical, and drying the treated piece of cotton fabric with a first heating source.","When the treated piece of cotton fabric has dried, the method includes heating the treated piece of cotton fabric with a second heating source while feeding the second heating source with nitrogen gas, removing the heated piece of fabric from the second heating source, and rinsing the heated piece of cotton fabric"],["TECHNICAL FIELD The present subject matter relates generally to production of activated carbon fabrics, and more particularly to a method for producing activated carbon fabrics from cotton fabrics.","BACKGROUND In recent years, the use of activated carbon has been increased in a number of industries, as it has been recognized as a highly effective absorbent material for removing gases, vapors, dyes and other organic compounds from vapor and liquid mediums.","As a result, activated carbon is often used in filters and masks for removing unwanted chemicals.","A wide range of carbonaceous precursors, such as coal, wood, byproducts and agricultural byproducts can be used to produce activated carbon.","The activated carbon produced from these materials, however, is in powder and/or granular form.","This limits the application of the produced activated carbon, as the form most often desired for use of activated carbon is a cloth or fabric.","To achieve this form of activated carbon, the powder and granular activated carbon is often converted to a fibrous or textile material by mixing it with a binding agent.","The process of conversion, however, is often time and labor consuming.","Moreover, because of the use of the binding agent, the resulting product often has a reduced active surface area, thereby decreasing the protentional filtering capabilities of the resulting product.","Therefore, a need exists for providing an improved method of producing activated carbon fabrics that is easy to use, reduces time and expense, and provides a higher quality product.","SUMMARY A method for producing an activated carbon fabric is provided.","In one implementation, the method includes preparing a piece of cotton fabric, washing the prepared piece of cotton fabric, treating the washed piece of cotton fabric with an acidic chemical, and drying the treated piece of cotton fabric with a first heating source.","When the treated piece of cotton fabric has dried, the method includes heating the treated piece of cotton fabric with a second heating source while feeding the second heating source with nitrogen gas, removing the heated piece of fabric from the second heating source, and rinsing the heated piece of cotton fabric BRIEF DESCRIPTION OF THE DRAWINGS Features of the subject technology are set forth in the appended claims.","However, for purpose of explanation, several implementations of the subject technology are set forth in the following figures.","FIG.","1 is a flow chart for a described process of producing activated carbon fabrics from cotton fabrics, according to an implementation.","FIG.","2 is a microscopic image of a portion of a sample activated carbon fabric produced according to the described process of producing activated carbon fabrics from cotton fabrics.","FIG.","3 is a graph showing the absorption rate of a sample activated carbon fabric produced according to the described process.","FIG.","4 is a graph showing a distribution of pore sizes in a sample activated carbon fabric produced according to the to the described process.","FIG.","5 is a graph showing an elemental activated carbon analysis of a sample activated carbon fabric produced according to the described process.","DETAILED DESCRIPTION In the following detailed description, numerous specific details are set forth by way of examples in order to provide a thorough understanding of the relevant teachings.","However, it should be apparent to those skilled in the art that the present teachings may be practiced without such details.","In other instances, well known methods, procedures, components, and/or circuitry have been described at a relatively high-level, without detail, in order to avoid unnecessarily obscuring aspects of the present teachings.","As part of the description, some of this disclosure's drawings represent structures and devices in block diagram form in order to avoid obscuring the invention.","In the interest of clarity, not all features of an actual implementation are described in this specification.","Moreover, the language used in this disclosure has been principally selected for readability and instructional purposes, and may not have been selected to delineate or circumscribe the inventive subject matter, resort to the claims being necessary to determine such inventive subject matter.","Reference in this disclosure to “one embodiment” or to “an embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the invention, and multiple references to “one embodiment” or “an embodiment” should not be understood as necessarily all referring to the same embodiment.","Recent demands for effective and efficient removal of unwanted chemicals from liquid and vapor mediums, such as air and water, have led to a substantial increase in use of activated carbon materials.","This increase has resulted in some recent developments in use of carbon-based waste products as the raw material for producing activated carbon.","Carbon-based waste products include agricultural byproducts and some forms of fiber and textiles.","The activated carbon produced by these processes, however, is generally in powder and granule form.","Utilizing activated carbon as a powder is generally more difficult than using an activated carbon fabric, as powder and granule activated carbons generally exhibit a low amount of flexibility, and are difficult to use in preparing an activated carbon fabric.","For example, a piece of activated carbon fabric can simply be used as a filter in an absorbent mask, whereas activated carbon in powder form has to be coated on the surface of the mask, giving rise to questions such as the most appropriate surface to use, the proper amount of coating to apply, and the proper binding agent to utilize.","These additional steps and issues result in more time needed for production and ultimately lead to higher costs.","Moreover, activated carbon fabrics (ACFs) have faster adsorption kinetics, higher efficiency, and a larger capacity for adsorption of different molecules and species than powder and granule activated carbons.","Despite these disadvantages, most currently produced activated carbon is still in powder and granule form as there are no alternative simple means for producing activated carbon fabrics.","A solution is proposed here to solve these issues and others by providing an improved method of producing activated carbon fabrics that utilizes a cotton fabric as a raw material.","Given the high percentage of cellulose in cotton, its use as a raw material in producing activated carbon fabrics is advantageous.","In one implementation, the method includes washing a piece of cotton fabric with a detergent before treating it with a chemical such as phosphoric acid, and then drying the treated fabric in an oven.","After the treated fabric has been dried, it may be placed into an electric furnace which is fed with a continuous flow of nitrogen gas as the temperature rises to heat the treated fabric.","Once removed from the furnace and rinsed with distilled water, the resulting product exhibits characteristics of an activated carbon fabric.","Thereby, cotton fabric can be converted directly to activated carbon fabric through a simple inexpensive and efficient process that is cost effective.","FIG.","1 is a flow diagram depicting an example method 100 used in producing activated carbon fabrics from cotton fabrics.","At 110, method 100 includes preparing a piece of cotton fabric according to preferred design requirements.","The preparations include selecting a piece of cotton fabric having a specific cotton count and weave.","In one implementation, a cotton fabric having approximately 19 counts per centimeters in length and 13 counts per centimeters in length is selected for achieving good results.","The selected cotton fabric has a plain weave such as taffeta, for example.","Other weave and cotton counts may be used in alternative implementations.","After selecting a fabric having the specific desired weave and density, the selected fabric may be cut into a desired size and shape as part of preparing the fabric.","The required size and shape of the cotton fabric may depend on design requirements of the desired activated carbon fabric, and/or may depend on any restrictions imposed by the shape and size of the oven and furnace needed to further process the fabric.","Once an appropriate cotton fabric is selected and cut into the desired shape and size, the cotton fabric is washed, at 120, with detergent, such as a non-ionic detergent for a pre-determined amount of time at a pre-determined temperature.","A non-ionic detergent may be used due to the water solubility and the superior ability in removing oil of these types detergents.","The pre-determined amount of time may be determined based on specific design requirements.","For example, the pre-determined amount of time is selected as approximately 30 minutes and the pre-determined temperature is selected as 60 degrees Celsius.","Once the cotton fabric is washed with the non-ionic detergent at the pre-determined temperature, it is rinsed before being dried.","In one implementation, the cotton fabric is rinsed with distilled water to prevent contamination with any other chemicals.","At 130, the now washed and dried cotton fabric is treated with an acidic chemical.","This may involve soaking the cotton fabric in an acidic chemical, such as phosphoric acid, for an extended period of time.","The extended period of time may be e.g., between 20 and 30 hours and is approximately 24 hours.","The ratio of the acidic chemical to the fabric may be 2 to 1.This means, for example, that an amount of phosphoric acid having twice as much weight as the cotton fabric is used for soaking the fabric.","In one implementation, the phosphoric acid used is an 85% aqueous solution.","Once the fabric has been soaked in the acidic chemical for an extended period of time, it is transferred, at 140, to a heating source such as an oven to dry.","The temperature of the oven may be between 105 to 110 degrees Celsius.","The fabric may remain in the oven until it is completely dry.","In one implementation, the fabric remains in the oven for approximately one hour.","The dried fabric is, at 150, transferred to another heating source such as an electric furnace to treat the fabric with a nitrogen gas.","This is done, for example, by feeding the electric furnace with a continuous flow of nitrogen gas while the temperature is gradually increased.","The temperature may be increased, for example, at a rate of approximately 7.5 degrees Celsius per minute until the furnace temperature reaches a desired temperature of, e.g., approximately 500 degrees Celsius.","Once the furnace temperature reaches the desired temperature, the fabric may be kept at the furnace for a specific amount of time until it is fully treated.","In one implementation, the specific amount of time may be approximately 30 minutes.","When the specific amount of time has passed, the furnace is turned off while the fabric is kept in the furnace until its temperature gradually returns to room temperature.","The resulting product is now an activated carbon fabric.","This product is then thoroughly rinsed, at 160, with distilled water having boiling temperature to completely remove the phosphoric acid from the fabric.","After being rinsed, the product may be dried in an oven, a dryer or at room temperature to produce the final product.","The resulting activated carbon fabric has a high capacity for absorption, maintains its fabric structure and therefore is ready to for use as a filter or in any other capacity.","Table 1 shows some characteristics of a sample activated carbon fabric produced according to the steps of method 100.TABLE 1 Characteristic Measured Quantity Iodine Value 595.2 mg I2/g C Surface Area 690.8 m2/g Total pore volume 0.32 cm3/g Average pore diameter 1.86 nm Percentage of return on weight 26.5 Percentage of return on size 38.4 Tensile Strength 0.259 MPa Bend Strength 0.122 mNμ FIG.","2 is a microscopic image of a portion of a sample activated carbon fabric produced according to the process discussed herein.","As can be seen in the image, the original weave and structure of the cotton fabric is still well preserved after going through the process of conversion from cotton to activated carbon.","Therefore, the activated carbon product produced as described herein continues to hold its fabric form and structure.","FIG.","3 is a graph of absorption isotherm for a sample activated carbon fabric produced according to the described process.","The graph shown in FIG.","3 specifically shows absorption of nitrogen by the sample activated carbon fabric.","According to the International Union of Pure and Applied Chemistry (IUPAC) classification, the graph of FIG.","3 is similar to a type I isotherm, often called Langmuir.","This is rarely seen in non-porous materials and is suitable for use with microporous compounds.","This isotherm has a hysteresis which indicates the presence of a mesoporous material.","This shows that the sample activated carbon fabric is highly absorbent.","FIG.","4 is a graph for distribution of pore sizes in a sample activated carbon fabric produced according to the process discussed herein.","The X axis represents pore radius (rp) in nanometers and the Y axis represents derivation of volume of pores to derivation of radius of pores (dVp/drp).","As shown in the graph, most of the pores of the sample activated carbon fabric are micropores in the range of between 1.21 to 3.5 nanometer.","In one implementation, the average diameter for pores of the sample activated carbon fabric is 1.86 nanometer.","The total volume of pores was determined to be 0.3216 cubic centimeters per gram.","FIG.","5 is a graph showing an elemental activated carbon analysis generated using an Energy-dispersive X-ray spectroscopy (EDX) method of a sample activated carbon fabric produced according to the process discussed herein.","As shown in the graph, the produced activated carbon fabric contains about 70.59% carbon, 46.26% oxygen and 0.6% phosphorus.","This shows the high efficiency of the carbonization process.","Due to the fact that cotton fabrics are available in different sizes and densities, raw materials for the process discussed herein are generally easily available and inexpensive.","Thus, the process of producing activated carbon fabrics from cotton fabrics is easy, efficient and inexpensive and results in producing high quality products that can be directly used for desired purposes.","The separation of various components in the examples described above should not be understood as requiring such separation in all examples, and it should be understood that the described components and systems can generally be integrated together in a single packaged into multiple systems.","While the foregoing has described what are considered to be the best mode and/or other examples, it is understood that various modifications may be made therein and that the subject matter disclosed herein may be implemented in various forms and examples, and that the teachings may be applied in numerous applications, only some of which have been described herein.","It is intended by the following claims to claim any and all applications, modifications and variations that fall within the true scope of the present teachings.","Unless otherwise stated, all measurements, values, ratings, positions, magnitudes, sizes, and other specifications that are set forth in this specification, including in the claims that follow, are approximate, not exact.","They are intended to have a reasonable range that is consistent with the functions to which they relate and with what is customary in the art to which they pertain.","The scope of protection is limited solely by the claims that now follow.","That scope is intended and should be interpreted to be as broad as is consistent with the ordinary meaning of the language that is used in the claims when interpreted in light of this specification and the prosecution history that follows and to encompass all structural and functional equivalents.","Notwithstanding, none of the claims are intended to embrace subject matter that fails to satisfy the requirement of Sections 101, 102, or 103 of the Patent Act, nor should they be interpreted in such a way.","Any unintended embracement of such subject matter is hereby disclaimed.","Except as stated immediately above, nothing that has been stated or illustrated is intended or should be interpreted to cause a dedication of any component, step, feature, object, benefit, advantage, or equivalent to the public, regardless of whether it is or is not recited in the claims.","It will be understood that the terms and expressions used herein have the ordinary meaning as is accorded to such terms and expressions with respect to their corresponding respective areas of inquiry and study except where specific meanings have otherwise been set forth herein.","Relational terms such as first and second and the like may be used solely to distinguish one entity or action from another without necessarily requiring or implying any actual such relationship or order between such entities or actions.","The terms “comprises,” “comprising,” or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus.","An element proceeded by “a” or “an” does not, without further constraints, preclude the existence of additional identical elements in the process, method, article, or apparatus that comprises the element.","The Abstract of the Disclosure is provided to allow the reader to quickly ascertain the nature of the technical disclosure.","It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims.","In addition, in the foregoing Detailed Description, it can be seen that various features are grouped together in various implementations for the purpose of streamlining the disclosure.","This method of disclosure is not to be interpreted as reflecting an intention that the claimed implementations require more features than are expressly recited in each claim.","Rather, as the following claims reflect, inventive subject matter lies in less than all features of a single disclosed implementation.","Thus, the following claims are hereby incorporated into the Detailed Description, with each claim standing on its own as a separately claimed subject matter."]],"string":"[\n [\n \"METHOD FOR PRODUCTION OF ACTIVATED CARBON FABRICS FROM COTTON\",\n \"An improved method of producing activated carbon fabrics from cotton fabrics involves washing a piece of cotton fabric with a detergent before soaking the washed piece of cotton fabric in an acidic chemical such as phosphoric acid for a specific amount of time, and then drying the soaked piece of cotton fabric in an oven.\",\n \"After the fabric has been dried, it is heated in a furnace which is fed with a flow of nitrogen gas as the temperature of the furnace is gradually increased to a pre-determined temperature and kept at the pre-determined temperature for an extended amount of time, before allowing the temperature to gradually return back to room temperature.\",\n \"After being removed from the furnace and being washed with distilled water to remove any remnants of phosphoric acid, the resulting product is an activated carbon fabric.\"\n ],\n [\n \"1.A method of producing an activated carbon fabric, comprising: preparing a piece of cotton fabric; washing the prepared piece of cotton fabric; treating the washed piece of cotton fabric with an acidic chemical; drying the treated piece of cotton fabric with a first heating source; when the treated piece of cotton fabric has dried, heating the treated piece of cotton fabric with a second heating source while feeding the second heating source with nitrogen gas; removing the heated piece of cotton fabric from the second heating source; and rinsing the heated piece of cotton fabric.\",\n \"2.The method of producing an activated carbon fabric of claim 1, wherein washing the piece of cotton fabric comprises washing the piece of cotton fabric with a non-ionic detergent and rinsing the piece of cotton fabric with distilled water.\",\n \"3.The method of producing an activated carbon fabric of claim 1, wherein the acidic chemical comprises phosphoric acid.\",\n \"4.The method of producing an activated carbon fabric of claim 3, wherein the acidic chemical comprises phosphoric acid comprises an 85% aqueous solution.\",\n \"5.The method of producing an activated carbon fabric of claim 1, wherein treating the washed piece of cotton fabric with an acidic chemical comprises soaking the washed piece of cotton fabric in an acidic chemical for an extended period of time.\",\n \"6.The method of producing an activated carbon fabric of claim 5, wherein the extended period of time comprises 24 hours.\",\n \"7.The method of producing an activated carbon fabric of claim 1, wherein the first heating source is an oven.\",\n \"8.The method of producing an activated carbon fabric of claim 7, wherein the treated piece of cotton fabric is dried in the oven at a temperature of between 105 to 110 degrees Celsius.\",\n \"9.The method of producing an activated carbon fabric of claim 7, wherein the treated piece of cotton fabric is dried in the oven for one hour.\",\n \"10.The method of producing an activated carbon fabric of claim 1, wherein the second heating source is a furnace.\",\n \"11.The method of producing an activated carbon fabric of claim 10, wherein the furnace is an electric furnace.\",\n \"12.The method of producing an activated carbon fabric of claim 10, wherein heating the first the treated piece of cotton fabric in the furnace comprises: feeding the furnace with the flow of the nitrogen gas while a temperature of the furnace is increased at a pre-determined rate to a desired temperature; keeping the treated piece of cotton fabric at the furnace at the desired temperature for a specific amount of time; and turning off the furnace and letting the treated piece of cotton fabric cool down in the furnace until a temperature of the treated piece of cotton fabric returns to room temperature.\",\n \"13.The method of producing an activated carbon fabric of claim 12, wherein the desired temperature is 500 degrees Celsius.\",\n \"14.The method of producing an activated carbon fabric of claim 12, wherein the specific amount of time is 30 minutes.\",\n \"15.The method of producing an activated carbon fabric of claim 1, wherein rinsing the treated piece of cotton fabric comprises rinsing the fabric with distilled water.\",\n \"16.The method of producing an activated carbon fabric of claim 15, wherein the distilled water is at a boiling temperature.\",\n \"17.The method of producing an activated carbon fabric of claim 1, further comprising drying the treated piece of cotton fabric after rinsing it.\",\n \"18.The method of producing an activated carbon fabric of claim 17, wherein drying the treated piece of cotton fabric after rinsing it occurs at an oven.\"\n ],\n [\n \" BACKGROUND In recent years, the use of activated carbon has been increased in a number of industries, as it has been recognized as a highly effective absorbent material for removing gases, vapors, dyes and other organic compounds from vapor and liquid mediums.\",\n \"As a result, activated carbon is often used in filters and masks for removing unwanted chemicals.\",\n \"A wide range of carbonaceous precursors, such as coal, wood, byproducts and agricultural byproducts can be used to produce activated carbon.\",\n \"The activated carbon produced from these materials, however, is in powder and/or granular form.\",\n \"This limits the application of the produced activated carbon, as the form most often desired for use of activated carbon is a cloth or fabric.\",\n \"To achieve this form of activated carbon, the powder and granular activated carbon is often converted to a fibrous or textile material by mixing it with a binding agent.\",\n \"The process of conversion, however, is often time and labor consuming.\",\n \"Moreover, because of the use of the binding agent, the resulting product often has a reduced active surface area, thereby decreasing the protentional filtering capabilities of the resulting product.\",\n \"Therefore, a need exists for providing an improved method of producing activated carbon fabrics that is easy to use, reduces time and expense, and provides a higher quality product.\"\n ],\n [\n \" SUMMARY A method for producing an activated carbon fabric is provided.\",\n \"In one implementation, the method includes preparing a piece of cotton fabric, washing the prepared piece of cotton fabric, treating the washed piece of cotton fabric with an acidic chemical, and drying the treated piece of cotton fabric with a first heating source.\",\n \"When the treated piece of cotton fabric has dried, the method includes heating the treated piece of cotton fabric with a second heating source while feeding the second heating source with nitrogen gas, removing the heated piece of fabric from the second heating source, and rinsing the heated piece of cotton fabric\"\n ],\n [\n \"TECHNICAL FIELD The present subject matter relates generally to production of activated carbon fabrics, and more particularly to a method for producing activated carbon fabrics from cotton fabrics.\",\n \"BACKGROUND In recent years, the use of activated carbon has been increased in a number of industries, as it has been recognized as a highly effective absorbent material for removing gases, vapors, dyes and other organic compounds from vapor and liquid mediums.\",\n \"As a result, activated carbon is often used in filters and masks for removing unwanted chemicals.\",\n \"A wide range of carbonaceous precursors, such as coal, wood, byproducts and agricultural byproducts can be used to produce activated carbon.\",\n \"The activated carbon produced from these materials, however, is in powder and/or granular form.\",\n \"This limits the application of the produced activated carbon, as the form most often desired for use of activated carbon is a cloth or fabric.\",\n \"To achieve this form of activated carbon, the powder and granular activated carbon is often converted to a fibrous or textile material by mixing it with a binding agent.\",\n \"The process of conversion, however, is often time and labor consuming.\",\n \"Moreover, because of the use of the binding agent, the resulting product often has a reduced active surface area, thereby decreasing the protentional filtering capabilities of the resulting product.\",\n \"Therefore, a need exists for providing an improved method of producing activated carbon fabrics that is easy to use, reduces time and expense, and provides a higher quality product.\",\n \"SUMMARY A method for producing an activated carbon fabric is provided.\",\n \"In one implementation, the method includes preparing a piece of cotton fabric, washing the prepared piece of cotton fabric, treating the washed piece of cotton fabric with an acidic chemical, and drying the treated piece of cotton fabric with a first heating source.\",\n \"When the treated piece of cotton fabric has dried, the method includes heating the treated piece of cotton fabric with a second heating source while feeding the second heating source with nitrogen gas, removing the heated piece of fabric from the second heating source, and rinsing the heated piece of cotton fabric BRIEF DESCRIPTION OF THE DRAWINGS Features of the subject technology are set forth in the appended claims.\",\n \"However, for purpose of explanation, several implementations of the subject technology are set forth in the following figures.\",\n \"FIG.\",\n \"1 is a flow chart for a described process of producing activated carbon fabrics from cotton fabrics, according to an implementation.\",\n \"FIG.\",\n \"2 is a microscopic image of a portion of a sample activated carbon fabric produced according to the described process of producing activated carbon fabrics from cotton fabrics.\",\n \"FIG.\",\n \"3 is a graph showing the absorption rate of a sample activated carbon fabric produced according to the described process.\",\n \"FIG.\",\n \"4 is a graph showing a distribution of pore sizes in a sample activated carbon fabric produced according to the to the described process.\",\n \"FIG.\",\n \"5 is a graph showing an elemental activated carbon analysis of a sample activated carbon fabric produced according to the described process.\",\n \"DETAILED DESCRIPTION In the following detailed description, numerous specific details are set forth by way of examples in order to provide a thorough understanding of the relevant teachings.\",\n \"However, it should be apparent to those skilled in the art that the present teachings may be practiced without such details.\",\n \"In other instances, well known methods, procedures, components, and/or circuitry have been described at a relatively high-level, without detail, in order to avoid unnecessarily obscuring aspects of the present teachings.\",\n \"As part of the description, some of this disclosure's drawings represent structures and devices in block diagram form in order to avoid obscuring the invention.\",\n \"In the interest of clarity, not all features of an actual implementation are described in this specification.\",\n \"Moreover, the language used in this disclosure has been principally selected for readability and instructional purposes, and may not have been selected to delineate or circumscribe the inventive subject matter, resort to the claims being necessary to determine such inventive subject matter.\",\n \"Reference in this disclosure to “one embodiment” or to “an embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the invention, and multiple references to “one embodiment” or “an embodiment” should not be understood as necessarily all referring to the same embodiment.\",\n \"Recent demands for effective and efficient removal of unwanted chemicals from liquid and vapor mediums, such as air and water, have led to a substantial increase in use of activated carbon materials.\",\n \"This increase has resulted in some recent developments in use of carbon-based waste products as the raw material for producing activated carbon.\",\n \"Carbon-based waste products include agricultural byproducts and some forms of fiber and textiles.\",\n \"The activated carbon produced by these processes, however, is generally in powder and granule form.\",\n \"Utilizing activated carbon as a powder is generally more difficult than using an activated carbon fabric, as powder and granule activated carbons generally exhibit a low amount of flexibility, and are difficult to use in preparing an activated carbon fabric.\",\n \"For example, a piece of activated carbon fabric can simply be used as a filter in an absorbent mask, whereas activated carbon in powder form has to be coated on the surface of the mask, giving rise to questions such as the most appropriate surface to use, the proper amount of coating to apply, and the proper binding agent to utilize.\",\n \"These additional steps and issues result in more time needed for production and ultimately lead to higher costs.\",\n \"Moreover, activated carbon fabrics (ACFs) have faster adsorption kinetics, higher efficiency, and a larger capacity for adsorption of different molecules and species than powder and granule activated carbons.\",\n \"Despite these disadvantages, most currently produced activated carbon is still in powder and granule form as there are no alternative simple means for producing activated carbon fabrics.\",\n \"A solution is proposed here to solve these issues and others by providing an improved method of producing activated carbon fabrics that utilizes a cotton fabric as a raw material.\",\n \"Given the high percentage of cellulose in cotton, its use as a raw material in producing activated carbon fabrics is advantageous.\",\n \"In one implementation, the method includes washing a piece of cotton fabric with a detergent before treating it with a chemical such as phosphoric acid, and then drying the treated fabric in an oven.\",\n \"After the treated fabric has been dried, it may be placed into an electric furnace which is fed with a continuous flow of nitrogen gas as the temperature rises to heat the treated fabric.\",\n \"Once removed from the furnace and rinsed with distilled water, the resulting product exhibits characteristics of an activated carbon fabric.\",\n \"Thereby, cotton fabric can be converted directly to activated carbon fabric through a simple inexpensive and efficient process that is cost effective.\",\n \"FIG.\",\n \"1 is a flow diagram depicting an example method 100 used in producing activated carbon fabrics from cotton fabrics.\",\n \"At 110, method 100 includes preparing a piece of cotton fabric according to preferred design requirements.\",\n \"The preparations include selecting a piece of cotton fabric having a specific cotton count and weave.\",\n \"In one implementation, a cotton fabric having approximately 19 counts per centimeters in length and 13 counts per centimeters in length is selected for achieving good results.\",\n \"The selected cotton fabric has a plain weave such as taffeta, for example.\",\n \"Other weave and cotton counts may be used in alternative implementations.\",\n \"After selecting a fabric having the specific desired weave and density, the selected fabric may be cut into a desired size and shape as part of preparing the fabric.\",\n \"The required size and shape of the cotton fabric may depend on design requirements of the desired activated carbon fabric, and/or may depend on any restrictions imposed by the shape and size of the oven and furnace needed to further process the fabric.\",\n \"Once an appropriate cotton fabric is selected and cut into the desired shape and size, the cotton fabric is washed, at 120, with detergent, such as a non-ionic detergent for a pre-determined amount of time at a pre-determined temperature.\",\n \"A non-ionic detergent may be used due to the water solubility and the superior ability in removing oil of these types detergents.\",\n \"The pre-determined amount of time may be determined based on specific design requirements.\",\n \"For example, the pre-determined amount of time is selected as approximately 30 minutes and the pre-determined temperature is selected as 60 degrees Celsius.\",\n \"Once the cotton fabric is washed with the non-ionic detergent at the pre-determined temperature, it is rinsed before being dried.\",\n \"In one implementation, the cotton fabric is rinsed with distilled water to prevent contamination with any other chemicals.\",\n \"At 130, the now washed and dried cotton fabric is treated with an acidic chemical.\",\n \"This may involve soaking the cotton fabric in an acidic chemical, such as phosphoric acid, for an extended period of time.\",\n \"The extended period of time may be e.g., between 20 and 30 hours and is approximately 24 hours.\",\n \"The ratio of the acidic chemical to the fabric may be 2 to 1.This means, for example, that an amount of phosphoric acid having twice as much weight as the cotton fabric is used for soaking the fabric.\",\n \"In one implementation, the phosphoric acid used is an 85% aqueous solution.\",\n \"Once the fabric has been soaked in the acidic chemical for an extended period of time, it is transferred, at 140, to a heating source such as an oven to dry.\",\n \"The temperature of the oven may be between 105 to 110 degrees Celsius.\",\n \"The fabric may remain in the oven until it is completely dry.\",\n \"In one implementation, the fabric remains in the oven for approximately one hour.\",\n \"The dried fabric is, at 150, transferred to another heating source such as an electric furnace to treat the fabric with a nitrogen gas.\",\n \"This is done, for example, by feeding the electric furnace with a continuous flow of nitrogen gas while the temperature is gradually increased.\",\n \"The temperature may be increased, for example, at a rate of approximately 7.5 degrees Celsius per minute until the furnace temperature reaches a desired temperature of, e.g., approximately 500 degrees Celsius.\",\n \"Once the furnace temperature reaches the desired temperature, the fabric may be kept at the furnace for a specific amount of time until it is fully treated.\",\n \"In one implementation, the specific amount of time may be approximately 30 minutes.\",\n \"When the specific amount of time has passed, the furnace is turned off while the fabric is kept in the furnace until its temperature gradually returns to room temperature.\",\n \"The resulting product is now an activated carbon fabric.\",\n \"This product is then thoroughly rinsed, at 160, with distilled water having boiling temperature to completely remove the phosphoric acid from the fabric.\",\n \"After being rinsed, the product may be dried in an oven, a dryer or at room temperature to produce the final product.\",\n \"The resulting activated carbon fabric has a high capacity for absorption, maintains its fabric structure and therefore is ready to for use as a filter or in any other capacity.\",\n \"Table 1 shows some characteristics of a sample activated carbon fabric produced according to the steps of method 100.TABLE 1 Characteristic Measured Quantity Iodine Value 595.2 mg I2/g C Surface Area 690.8 m2/g Total pore volume 0.32 cm3/g Average pore diameter 1.86 nm Percentage of return on weight 26.5 Percentage of return on size 38.4 Tensile Strength 0.259 MPa Bend Strength 0.122 mNμ FIG.\",\n \"2 is a microscopic image of a portion of a sample activated carbon fabric produced according to the process discussed herein.\",\n \"As can be seen in the image, the original weave and structure of the cotton fabric is still well preserved after going through the process of conversion from cotton to activated carbon.\",\n \"Therefore, the activated carbon product produced as described herein continues to hold its fabric form and structure.\",\n \"FIG.\",\n \"3 is a graph of absorption isotherm for a sample activated carbon fabric produced according to the described process.\",\n \"The graph shown in FIG.\",\n \"3 specifically shows absorption of nitrogen by the sample activated carbon fabric.\",\n \"According to the International Union of Pure and Applied Chemistry (IUPAC) classification, the graph of FIG.\",\n \"3 is similar to a type I isotherm, often called Langmuir.\",\n \"This is rarely seen in non-porous materials and is suitable for use with microporous compounds.\",\n \"This isotherm has a hysteresis which indicates the presence of a mesoporous material.\",\n \"This shows that the sample activated carbon fabric is highly absorbent.\",\n \"FIG.\",\n \"4 is a graph for distribution of pore sizes in a sample activated carbon fabric produced according to the process discussed herein.\",\n \"The X axis represents pore radius (rp) in nanometers and the Y axis represents derivation of volume of pores to derivation of radius of pores (dVp/drp).\",\n \"As shown in the graph, most of the pores of the sample activated carbon fabric are micropores in the range of between 1.21 to 3.5 nanometer.\",\n \"In one implementation, the average diameter for pores of the sample activated carbon fabric is 1.86 nanometer.\",\n \"The total volume of pores was determined to be 0.3216 cubic centimeters per gram.\",\n \"FIG.\",\n \"5 is a graph showing an elemental activated carbon analysis generated using an Energy-dispersive X-ray spectroscopy (EDX) method of a sample activated carbon fabric produced according to the process discussed herein.\",\n \"As shown in the graph, the produced activated carbon fabric contains about 70.59% carbon, 46.26% oxygen and 0.6% phosphorus.\",\n \"This shows the high efficiency of the carbonization process.\",\n \"Due to the fact that cotton fabrics are available in different sizes and densities, raw materials for the process discussed herein are generally easily available and inexpensive.\",\n \"Thus, the process of producing activated carbon fabrics from cotton fabrics is easy, efficient and inexpensive and results in producing high quality products that can be directly used for desired purposes.\",\n \"The separation of various components in the examples described above should not be understood as requiring such separation in all examples, and it should be understood that the described components and systems can generally be integrated together in a single packaged into multiple systems.\",\n \"While the foregoing has described what are considered to be the best mode and/or other examples, it is understood that various modifications may be made therein and that the subject matter disclosed herein may be implemented in various forms and examples, and that the teachings may be applied in numerous applications, only some of which have been described herein.\",\n \"It is intended by the following claims to claim any and all applications, modifications and variations that fall within the true scope of the present teachings.\",\n \"Unless otherwise stated, all measurements, values, ratings, positions, magnitudes, sizes, and other specifications that are set forth in this specification, including in the claims that follow, are approximate, not exact.\",\n \"They are intended to have a reasonable range that is consistent with the functions to which they relate and with what is customary in the art to which they pertain.\",\n \"The scope of protection is limited solely by the claims that now follow.\",\n \"That scope is intended and should be interpreted to be as broad as is consistent with the ordinary meaning of the language that is used in the claims when interpreted in light of this specification and the prosecution history that follows and to encompass all structural and functional equivalents.\",\n \"Notwithstanding, none of the claims are intended to embrace subject matter that fails to satisfy the requirement of Sections 101, 102, or 103 of the Patent Act, nor should they be interpreted in such a way.\",\n \"Any unintended embracement of such subject matter is hereby disclaimed.\",\n \"Except as stated immediately above, nothing that has been stated or illustrated is intended or should be interpreted to cause a dedication of any component, step, feature, object, benefit, advantage, or equivalent to the public, regardless of whether it is or is not recited in the claims.\",\n \"It will be understood that the terms and expressions used herein have the ordinary meaning as is accorded to such terms and expressions with respect to their corresponding respective areas of inquiry and study except where specific meanings have otherwise been set forth herein.\",\n \"Relational terms such as first and second and the like may be used solely to distinguish one entity or action from another without necessarily requiring or implying any actual such relationship or order between such entities or actions.\",\n \"The terms “comprises,” “comprising,” or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus.\",\n \"An element proceeded by “a” or “an” does not, without further constraints, preclude the existence of additional identical elements in the process, method, article, or apparatus that comprises the element.\",\n \"The Abstract of the Disclosure is provided to allow the reader to quickly ascertain the nature of the technical disclosure.\",\n \"It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims.\",\n \"In addition, in the foregoing Detailed Description, it can be seen that various features are grouped together in various implementations for the purpose of streamlining the disclosure.\",\n \"This method of disclosure is not to be interpreted as reflecting an intention that the claimed implementations require more features than are expressly recited in each claim.\",\n \"Rather, as the following claims reflect, inventive subject matter lies in less than all features of a single disclosed implementation.\",\n \"Thus, the following claims are hereby incorporated into the Detailed Description, with each claim standing on its own as a separately claimed subject matter.\"\n ]\n]"},"source":{"kind":"string","value":"Patent_15871985"}}},{"rowIdx":4493973,"cells":{"text":{"kind":"list like","value":[["METHODS FOR PRODUCING EMULSIFIERS FOR OIL-BASED DRILLING FLUIDS","Methods for making emulsifiers, emulsified drilling fluids, and methods for using the same are provided.","In one or more embodiments, the method for making an emulsifier can include mixing a tall oil and a triamide.","The triamide can have the chemical formula: where: x, y, and z are integers independently selected from 1 to 10, R1 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl, R2 is H or independently selected for each [(CH2)xNR2(CH2)y] unit, where R4 is a C1-C3 alkylene or a C1-C3 alkylene alcohol, and where at least one R2 is and R3 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl."],["1.An emulsifier, comprising: a tall oil component; and a triamide component.","2.The emulsifier of claim 1, wherein the triamide component comprises a triamide having the chemical formula: wherein: x, y, and z are integers independently selected from 1 to 10, R1 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl, R2 is H or independently selected for each [(CH2)xNR2(CH2)y] unit, wherein R4 is a C1-C3 alkylene or a C1-C3 alkylene alcohol, and wherein at least one R2 is and R3 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl.","3.The emulsifier of claim 1, wherein the triamide component comprises an alkali metal salt of a triamide, an alkaline earth metal salt of a triamide, or a mixture thereof.","4.The emulsifier of claim 1, wherein the triamide component comprises an alkali metal salt of a triamide, and wherein the triamide the chemical formula: wherein: x, y, and z are integers independently selected from 1 to 10, R1 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl, R2 is H or independently selected for each [(CH2)xNR2(CH2)y] unit, wherein R4 is a C1-C3 alkylene or a C1-C3 alkylene alcohol, and wherein at least one R2 is and R3 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl.","5.The emulsifier of claim 4, wherein R4 is an ethanediyl group (—CH2CH2—).","6.The emulsifier of claim 1, wherein the triamide component comprises an alkaline earth metal salt of a triamide, and wherein the triamide the chemical formula: wherein: x, y, and z are integers independently selected from 1 to 10, R2 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl, R2 is H or independently selected for each [(CH2)xNR2(CH2)y] unit, wherein R4 is a C1-C3 alkylene or a C1-C3 alkylene alcohol, and wherein at least one R2 is and R3 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl.","7.The emulsifier of claim 6, wherein R4 is an ethanediyl group (—CH2CH2—).","8.The emulsifier of claim 1, wherein the tall oil component comprises a tall oil.","9.The emulsifier of claim 1, wherein the tall oil component comprises an alkali metal salt of a tall oil.","10.The emulsifier of claim 1, wherein the tall oil component comprises an alkaline earth metal salt of a tall oil.","11.The emulsifier of claim 1, wherein the emulsifier is a spray dried emulsifier and has an average particle size of about 1 μm to about 75 μm.","12.The emulsifier of claim 1, wherein the tall oil comprises a crude tall oil, a distillate tall oil, a tall oil bottoms, or a mixture thereof.","13.The method of claim 1, wherein the tall oil component comprises a modified tall oil produced by reacting a tall oil and an α,β unsaturated carboxylic acid or an α,β unsaturated acid anhydride.","14.The method of claim 1, wherein the tall oil component comprises a mixture of a first tall oil distillate fraction and a second tall oil distillate fraction comprising about 45 wt % to about 90 wt % of fatty acids and about 10 wt % to about 55 wt % of rosin acids, based on the combined weight of the first tall oil distillate fraction and the second tall oil distillate fraction.","15.A process for making an emulsifier, comprising: mixing a tall oil component and a triamide component to produce a mixture; and spray drying the mixture to produce a spray dried emulsifier.","16.The process of claim 15, wherein the triamide component is produced by reacting a diamidoamine with a saturated dicarboxylic acid, a saturated acid anhydride, or a mixture thereof, and wherein the tall oil component is produced by reacting a tall oil and an α,β unsaturated carboxylic acid or an α,β unsaturated acid anhydride.","17.The process of claim 15, further comprising neutralizing the mixture to produce a neutralized mixture, wherein the neutralized mixture is spray dried to produce the spray dried emulsifier.","18.A drilling fluid, comprising: an oil phase; an aqueous phase, and a spray dried emulsifier comprising a mixture of a tall oil component and a triamide component.","19.The drilling fluid of claim 19, wherein: the oil phase comprises paraffins, olefins, aromatics, naphthalenes, or a mixture thereof, the aqueous phase comprises a brine solution containing sodium chloride, potassium chloride, magnesium chloride, calcium chloride, or a mixture thereof, the triamide component comprises an alkali metal salt of a triamide, an alkaline earth metal salt of a triamide, or a mixture thereof, and the tall oil component comprises an alkali metal salt of a tall oil, an alkaline earth metal salt of a tall oil, or a mixture thereof.","20.The drilling fluid of claim 19, wherein the drilling fluid comprises about 0.2 wt % to about 5 wt % of the spray dried emulsifier and about 5 wt % to about 40 wt % of the aqueous phase, based on a combined weight of the oil phase, the aqueous phase, and the spray dried emulsifier."],[" BACKGROUND "],[" SUMMARY Methods for making emulsifiers, emulsified drilling fluids, and methods for using the same are provided.","In one or more embodiments, the method for making an emulsifier can include mixing a tall oil and a triamide.","The triamide can have the general chemical formula, Formula (I): where: x, y, and z are integers independently selected from 1 to 10, R 1 is a C 8 -C 20 alkyl, a C 8 -C 20 alkenyl, a C 8 -C 20 dialkenyl, or a C 8 -C 20 alkynyl, R 2 is H or independently selected for each [CH 2 ) x NR 2 (CH 2 ) y ] unit, where R 4 is a C 1 -C 3 alkylene or a C 1 -C 3 alkylene alcohol, and where at least one R 2 is and R 3 is a C 8 -C 20 alkyl, a C 8 -C 20 alkenyl, a C 8 -C 20 dialkenyl, or a C 8 -C 20 alkynyl.","In some embodiments, the method for making an emulsifier can include mixing a triamide and a tall oil.","The triamide can be prepared by reacting a diamidoamine with a saturated dicarboxylic acid, a saturated acid anhydride, or a mixture thereof.","The method can also include spray drying the emulsifier to provide a spray dried emulsifier.","The method for making a drilling fluid can include mixing an oil phase, an aqueous phase, and a spray dried emulsifier to produce a drilling fluid.","The spray dried emulsifier can include a mixture of a tall oil and a triamide, where the triamide can have Formula (I).","detailed-description description=\"Detailed Description\" end=\"lead\"?"],["CROSS-REFERENCE TO RELATED APPLICATION This application is a continuation of co-pending U.S. patent application Ser.","No.","14/461,460, filed on Aug. 18, 2014, which claims priority to U.S.","Provisional Patent Application No.","61/867,328, filed Aug. 19, 2013, which are both incorporated by reference herein.","BACKGROUND Field Embodiments described generally relate to methods for making emulsifiers that can include one or more tall oils and one or more triamides, emulsified drilling fluids, and methods for using same.","Description of the Related Art The oil and gas industry has used drilling fluids or “drilling muds” for a number of years to tap subterranean deposits of natural resources.","As the total reserves of oil diminish, it has become necessary to drill in areas that were previously inaccessible due to technological or economic difficulties.","This has led to the widespread use of oil-based drilling fluids or invert emulsion drilling fluids, which offer greater thermal and chemical stability than water-based fluids, allowing for drilling at extended depths and in other demanding services, such as those involving exposure to high electrolyte concentrations and soluble gases.","For example, invert emulsion drilling fluids have been used successfully in drilling hot (e.g., greater than 150° C.) formations as well as those containing hydrogen sulfide.","Also, to maximize recovery from each platform in offshore drilling, invert emulsion drilling fluids are favored due to their effectiveness for drilling deviated wells (e.g., angled wells).","In particular, the high lubricity of invert emulsion drilling fluids is necessary because of the increased torque exerted on the drill string in deviated drilling.","Invert emulsion drilling fluids are typically formed by blending a hydrocarbon oil with water or brine under high shear conditions and in the presence of a suitable emulsifier.","The emulsifier is required not only to form a stable dispersion of water droplets in the oil phase, but also to maintain any solids such as weighting material additives (e.g., barites) or drill cuttings in an oil-wet state.","With space at some well sites limited, such as on offshore platforms, and with increasing costs of transport of materials to a well site, there is industry wide interest particularly in drilling fluid compositions that can be formulated and maintained (e.g., stored) with minimal or fewer quantities of solvent and other additives, compared to prior art compositions.","There is a need, therefore, for improved emulsifiers for use in invert emulsions that can be used, for example, in oil well drilling.","SUMMARY Methods for making emulsifiers, emulsified drilling fluids, and methods for using the same are provided.","In one or more embodiments, the method for making an emulsifier can include mixing a tall oil and a triamide.","The triamide can have the general chemical formula, Formula (I): where: x, y, and z are integers independently selected from 1 to 10, R1 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl, R2 is H or independently selected for each [CH2)xNR2(CH2)y] unit, where R4 is a C1-C3 alkylene or a C1-C3 alkylene alcohol, and where at least one R2 is and R3 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl.","In some embodiments, the method for making an emulsifier can include mixing a triamide and a tall oil.","The triamide can be prepared by reacting a diamidoamine with a saturated dicarboxylic acid, a saturated acid anhydride, or a mixture thereof.","The method can also include spray drying the emulsifier to provide a spray dried emulsifier.","The method for making a drilling fluid can include mixing an oil phase, an aqueous phase, and a spray dried emulsifier to produce a drilling fluid.","The spray dried emulsifier can include a mixture of a tall oil and a triamide, where the triamide can have Formula (I).","DETAILED DESCRIPTION Methods for making emulsifiers, emulsified drilling fluids, and methods for using the same are provided.","In one or more embodiments, the emulsifier can be made by mixing, blending, or otherwise combining one or more tall oils and one or more triamides.","The one or more triamides can be represented by the general chemical formula, Formula (I): where: x, y, and z are integers independently selected from 1 to 10, R2 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl, R2 is H or independently selected for each [CH2)xNR2(CH2)y] unit, where R4 is a C1-C3 alkylene or a C1-C3 alkylene alcohol, and where at least one R2 is and R3 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl.","The C1-C3 alkylene for R4 can include, but is not limited to, a methylene or methanediyl group (—CH2—), an ethylene or ethanediyl group (—CH2CH2—), and a propylene or propanediyl group (—CH2CH2CH2—), which provides a saturated alkane moiety in the triamide.","The C1-C3 alkylene alcohol for R4 can include, but is not limited to, a methylene or methanediyl alcohol group (—C(OH)H—), an ethylene or ethanediyl alcohol group (—CH2C(OH)H—), and a propylene or propanediyl alcohol group (—CH2C(OH)HCH2— or —CH2CH2C(OH)H—), which provides a saturated alkane alcohol moiety in the triamide.","In some embodiments, the emulsifier can be used for oil-based drilling fluids.","It has been surprisingly and unexpectedly discovered that when R4 is a C1-C3 alkylene or a C1-C3 alkylene alcohol, e.g., a saturated carbon chain, the oil-based drilling fluids can exhibit one or more of the following properties: flatter low end rheology, lower high end rheology, higher electrical stability, lower plastic viscosity, lower gel strengths, and lower fluid loss to the subterranean formation, as compared to the same emulsifier, but having an unsaturated R4, e.g., an R4 having at least one carbon-carbon double bond.","For example, the emulsifier having R4 as a C1-C3 alkylene or a C1-C3 alkylene alcohol can improve the low end rheology, the high end rheology, the electrical stability, the gel strengths, plastic viscosity, fluid break-through, and/or the fluid loss by about 0.2%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, or about 10%, or more as compared to the same emulsifier but having an unsaturated R4, such as when R4 is alkenylene (e.g., —(CnH2n-2)—, where n is 1, 2, or 3).","The one or more tall oils and the one or more triamides of the emulsifier can be combined with one another in any ratio.","For example, the weight ratio of the triamide to the tall oil can be about 99:1, about 90:10, about 80:20, about 70:30, about 60:40, or about 50:50 to about 40:60, about 30:70, about 20:80, about 10:90, or about 1:99.In another example, the weight ratio of the triamide to tall oil can be about 0.5:1, about 1:1, about 2:3, about 3:7, or about 1:4.In another example, the weight ratio of the triamide to tall oil can be about 0.1:1 to about 3:1, about 0.2:1 to about 2.8:1, about 0.3:1 to about 2.5:1, about 0.4:1 to about 2.2:1, about 0.5:1 to about 2:1, about 0.3:1 to about 2:1, about 1:1 to about 3:1, about 0.4:1 to about 1:1, about 0.4:1 to about 0.7:1, or about 0.3:1 to about 1:1.In some embodiments, the emulsifier can have an acid value of about 100 mg of KOH, about 125 mg of KOH, or about 150 mg of KOH to about 250 mg of KOH, about 175 mg of KOH, about 200 mg of KOH, per gram of emulsifier.","For example, the emulsifier can have an acid value of about 100 mg of KOH to about 150 mg of KOH, about 125 mg of KOH to about 175 mg of KOH, about 170 mg of KOH to about 200 mg of KOH, about 170 mg of KOH to about 225 mg of KOH, about 165 mg of KOH to about 230 mg of KOH, about 180 mg of KOH to about 220 mg of KOH, about 200 mg of KOH to about 250 mg of KOH, about 225 mg of KOH to about 250 mg of KOH, or about 250 mg of KOH to about 300 mg of KOH, per gram of emulsifier.","In another example, the emulsifier can have an acid value of at least 100 mg of KOH, at least 110 mg of KOH, at least 120 mg of KOH, at least 130 mg KOH, at least 150 mg KOH, or at least 175 mg KOH.","In another example, the emulsifier can have an acid value of less than 220 mg KOH, less than 170 mg KOH, or less than 150 mg KOH.","As used herein, the term “acid value” refers to the mass of potassium hydroxide (KOH) in milligrams that is required to neutralize one gram of a reaction mixture or a composition.","For example, the acid value of the emulsifier refers to the amount of KOH in milligrams required to neutralize one gram of the emulsifier.","The acid value can be used as a measure of the amount of carboxylic acid groups in a reaction mixture or a composition.","In a typical procedure, a known amount of the composition is dissolved in organic solvent and titrated with a solution of potassium hydroxide of known concentration.","The acid value can be determined by using a potassium hydride solution that contains phenolphthalein as a color indicator or using potentiometric analysis.","Standard methods used for determining acid value include ASTM D 465-05 and AOCS Te 1a-64.The rheology, electrical stability, gel strengths, plastic viscosity, yield point, high temperature/high pressure, fluid break-through, and fluid loss can be tested according to the API Recommended Practice Standard 13B-2, Third Edition, February 1998.The drilling fluid can have a rheology of about 3, about 5, or about 7 to about 15, about 17, or about 20, after hot roll at 3 rotations per minute (rpm) at 150° F. For example, the drilling fluid can have a rheology of about 4 to about 7, about 5 to about 10, about 6 to about 17, about 8 to about 15, or about 8 to about 28, after hot roll at 3 rpm at 150° F. The drilling fluid can have a rheology of about 3, about 5, or about 7 to about 15, about 17, about 23, about 27, or about 30, after hot roll at 6 rpm at 150° F. For example, the drilling fluid can have a rheology of about 4 to about 7, about 5 to about 10, about 6 to about 17, about 8 to about 15, or about 6 to about 28, after hot roll at 6 rpm at 150° F. The drilling fluid can have a rheology of about 45, about 50, or about 55 to about 70, about 75, about 85, after hot roll at 600 rpm at 150° F. For example, the drilling fluid can have a rheology of about 40 to about 70, about 50 to about 67, about 50 to about 70, or about 55 to about 85, after hot roll at 600 rpm at 150° F. The drilling fluid containing the emulsifier can have a ten second gel strength of about 3 lb/100 ft2, about 5 lb/100 ft2, or about 7 lb/100 ft2 to about 15 lb/100 ft2, about 17 lb/100 ft2, about 30 lb/100 ft2, after hot roll at 150° F. For example, the drilling fluid can have a ten second gel strength of about 4 lb/100 ft2 to about 7 lb/100 ft2, about 5 lb/100 ft2 to about 10 lb/100 ft2, about 6 lb/100 ft2 to about 17 lb/100 ft2, about 8 lb/100 ft2 to about 15 lb/100 ft2, or about 14 lb/100 ft2to about 28 lb/100 ft2, after hot roll at 150° F. The drilling fluid containing the emulsifier can have a ten minute gel strength of about 3 lb/100 ft2, about 5 lb/100 ft2, or about 7 lb/100 ft2 to about 15 lb/100 ft2, about 17 lb/100 ft2, about 30 lb/100 ft2, after hot roll at 150° F. For example, the drilling fluid can have a ten minute gel strength of about 4 lb/100 ft2 to about 7 lb/100 ft2, about 5 lb/100 ft2 to about 10 lb/100 ft2, about 6 lb/100 ft2 to about 17 lb/100 ft2, about 8 lb/100 ft2 to about 15 lb/100 ft2, or about 14 lb/100 ft2 to about 28 lb/100 ft2, after hot roll at 150° F. The drilling fluid containing the emulsifier can have a plastic viscosity of about 15 cP, about 17 cP, or about 19 cP to about 25 cP, about 27 cP, about 30 cP, after hot roll at 150° F. For example, the drilling fluid can have a plastic viscosity of about 15 cP to about 17 cP, about 5 cP to about 10 cP, about 6 cP to about 17 cP, about 8 cP to about 15 cP, or about 14 cP to about 28 cP, after hot roll at 150° F. The drilling fluid containing the emulsifier can have a yield point of about 3 lb/100 ft2, about 5 lb/100 ft2, or about 7 lb/100 ft2 to about 15 lb/100 ft2, about 17 lb/100 ft2, about 30 lb/100 ft2, after hot roll at 150° F. For example, the drilling fluid can have a yield point of about 4 lb/100 ft2 to about 7 lb/100 ft2, about 5 lb/100 ft2 to about 10 lb/100 ft2, about 6 lb/100 ft2 to about 17 lb/100 ft2, about 8 lb/100 ft2 to about 15 lb/100 ft2, or about 8 lb/100 ft2 to about 28 lb/100 ft2, after hot roll at 150° F. The drilling fluid containing the emulsifier can have higher electrical stability.","The drilling fluid containing the emulsifier can have an electrical stability of about 600 V, about 700 V, or about 725 V to about 800 V, about 1,000 V, or about 1,200 V, at 150° F. For example, the drilling fluid containing the emulsifier can have an electrical stability of about 600 V to about 650 V, about 650 V to about 700 V, about 675 V to about 750 V, about 700 V to about 760 V, about 725 V to about 850 V, about 825 V to about 950 V, about 925 V to about 1,100 V, or about 1,000 V to about 1,200 V, at 150° F. The drilling fluid containing the emulsifier can have high temperature/high pressure fluid loss of about 5 mL, about 6 mL, or about 7 mL to about 10 mL, about 12 mL, about 14 mL, after hot roll at 150° F. For example, the drilling fluid can have a fluid loss of about 4 mL to about 7 mL, about 5 mL to about 10 mL, about 6 mL to about 11 mL, or about 8 mL to about 14 mL, after hot roll at 150° F. The drilling fluid containing the emulsifier can exhibit minimal water break-through under high temperature/high pressure testing conditions.","The drilling fluid containing the emulsifier can have a water break-through value of about 0 mL, about 0.1 mL, or about 0.2 mL to about 0.5 mL, at high temperature/high pressure testing conditions.","For example, the drilling fluid containing the emulsifier can have a water break-through value of about 0 mL to about 0.1 mL, about 0.1 mL to about 0.2 mL, about 0.2 mL to about 0.3 mL, about 0.3 mL to about 0.4 mL, or about 0.4 mL to about 0.5 mL, at high temperature/high pressure testing conditions.","The compounds of Formula (I) can be made using one or more different synthetic routes.","One exemplary synthetic route can include sequential condensation reactions as shown in Scheme (I) below.","More particularly, a polyamine can be reacted with fatty acids to produce an amidoamine product.","The amidoamine product can be reacted with a succinic anhydride to produce a triamide.","In the specific embodiment depicted in Scheme (I), two molecules of the same kind of fatty acid are reacted with diethylenetriamine as the polyamine to form a diamidoamine or “intermediate product.” In a subsequent condensation reaction, the diamidoamine is reacted with succinic anhydride as the saturated dicarboxylic acid to produce a triamide.","Exemplary Scheme (I) is as follows: It can be seen that the triamide depicted in Scheme (I) has the molecular structure of Formula (I), where R1 and R4 are the same.","The reaction conditions, e.g., heating, can be controlled to favor the more thermodynamically stable amide product.","Any of the amine functional groups on the polyamine can undergo a condensation reaction with the carboxylic acid group of the fatty acid; however, the primary amines can be more kinetically favored than the secondary amines on the polyamine.","By controlling the reaction conditions, such as the concentration of the reactants, the reaction of one fatty acid molecule for every primary amine on the polyamine can be favored.","A thermodynamically and kinetically favored diamidoamine has been depicted in Reaction 1 of Scheme (I).","The diamidoamine can then be reacted with a saturated dicarboxylic acid and/or a saturated acid anhydride.","Reaction 2 of Scheme (I) depicts a condensation reaction between the diamidoamine and succinic anhydride.","At least one of the acyl moieties on the succinic anhydride can react with at least one of the secondary amine functional groups on the diamidoamine (for diethylenetriamine only one secondary amine is present) to form a third amide group.","The second acyl moiety on the anhydride can react with a second diamidoamine in the reaction mixture, e.g., two diamidoamine molecules can react with one anhydride compound.","By controlling the reaction conditions, however, such as the concentrations of the reactants, the reaction between one diamidoamine molecule and one dicarboxylic acid or acid anhydride molecule can be favored.","Also, if the reaction is performed with an acid anhydride compound instead of a dicarboxylic acid compound, a lower temperature can be used, which leads to less cross-linking between diamidoamines.","In one or more examples, the reaction product can be triamide, as illustrated in Reaction 2 of Scheme (I).","In one or more examples, after a single condensation reaction of the fatty acid and the polyamine, a self-cyclization reaction can produce an imidazoline (e.g., a 1-aminoalkyl-2-alkyl-2-imidazoline).","For clarity, Reaction 3 has been included to show an exemplary imidazoline product when the reactant polyamine is diethylenetriamine.","The reaction mixture for the diamidoamine and, if the subsequent reaction is performed in a single pot, the reaction mixture for the triamide can also include the imidazoline product.","The primary amine of the imidazoline product can also react with the saturated dicarboxylic acid and/or saturated acid anhydride.","Because the imidazoline product is less effective as an emulsifier, the reaction conditions, such as reaction temperature, can be chosen to limit the imidazoline reaction product.","Exemplary reaction conditions for limiting the imidazoline reaction product can include those discussed and described in U.S. Pat.","No.","3,758,493.One or more fatty acids, one or more polyamines, and one or more liquid media can be mixed to from a diamidoamine reaction mixture.","The molar ratio of the carboxylic acid group on the fatty acid to the primary amine groups on the polyamine can be used to favor a reaction between one fatty acid molecule for every primary amine group on the polyamine.","For example, e molar ratio of the carboxylic acid group to the primary amine group can be about 0.5:1 to about 1.1:1.In another example, the molar ratio of the carboxylic acid group to the primary amine group can be about 0.5:1 to about 0.7:1, about 0.6:1 to about 0.8:1, about 0.7:1 to about 1:1, about 0.9:1 to about 1:1, or about 0.8:1 to about 1.1:1.The diamidoamine reaction mixture can be heated to a temperature of about 130° C., about 140° C., about 145° C. to about 170° C., about 180° C., or about 200° C. For example, the reaction temperature can be about 140° C. to about 150° C., about 145° C. to about 155° C., about 155° C. to about 165° C., about 160° C. to about 170° C., about 155° C. to about 170° C., about 160° C. to about 190° C., or about 180° C. to about 200° C. The diamidoamine reaction mixture of the fatty acids and the polyamine can be heated for, or otherwise have a reaction time of, about 0.5 hours, about 1 hour, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, about 7 hours, about 8 hours, about 9 hours, about 10 hours, about 11 hours, about 12 hours, or greater.","For example, the fatty acids and the polyamine can be heated or reacted for about 0.7 hours to about 1.3 hours, about 0.7 hours to about 1.3 hours, about 1 hour to about 3 hours, about 1.5 hours to about 4 hours, about 2 hours to about 5 hours, about 3 hours to about 7 hours, about 5 hours to about 8 hours, about 6 hours to about 10 hours, about 8 hours to about 12 hours.","The fatty acids and the polyamine can be reacted until a desired acid value is obtained.","The diamidoamine reaction mixture can have an acid value of about 3 mg of KOH, about 5 mg of KOH, or about 7 mg of KOH to about 15 mg of KOH, about 20 mg of KOH, or about 25 mg of KOH, per gram of diamidoamine reaction mixture.","For example, the diamidoamine reaction mixture can have an acid value of about 3 mg of KOH to about 5 mg of KOH, about 4 mg of KOH to about 8 mg of KOH, about 7 mg of KOH to about 12 mg of KOH, about 9 mg of KOH to about 15 mg of KOH, about 10 mg of KOH to about 16 mg of KOH, about 14 mg of KOH to about 20 mg of KOH, about 16 mg of KOH to about 25 mg of KOH, per gram of diamidoamine reaction mixture.","The diamidoamine reaction mixture can include a solvent or diluent, also referred to as “liquid medium.” The diamidoamine reaction can also be performed neat so the diamidoamine reaction mixture can be free of solvent or liquid medium.","The diamidoamine reaction mixture can have a liquid medium concentration of about 0.1 wt %, about 1 wt %, or about 3 wt % to about 10 wt %, about 15 wt %, or about 20 wt %, based on the combined weight of the fatty acids, the polyamines, and the liquid medium.","In another example, the diamidoamine reaction mixture can have a liquid medium concentration of about 0.1 wt % to about 3 wt %, about 0.1 wt % to about 4 wt %, about 1 wt % to about 6 wt %, about 3 wt % to about 8 wt %, about 7 wt % to about 14 wt %, about 11 wt % to about 17 wt %, or about 12 wt % to about 20 wt %, the polyamines, and the liquid medium.","During the reaction, the liquid medium can be distilled or evaporated from the diamidoamine reaction mixture, which can change the concentration of the liquid medium.","The diamidoamine reaction mixture can have a solids content of about 80 wt %, about 85 wt %, or about 90 wt % to about 95 wt %, about 98 wt %, or about 100 wt % (e.g., where the solvent-free system has 100 wt % solids), based on the total weight of the reaction mixture.","In another example, the diamidoamine reaction mixture can have a solids content of about 80 wt % to about 85 wt %, about 85 wt % to about 90 wt %, about 90 wt % to about 95 wt %, about 94 wt % to about 98 wt %, about 96 wt % to about 99 wt %, or about 96 wt % to about 100 wt %, based on the total weight of the reaction mixture.","As used herein, the solids content, as understood by those skilled in the art, can be measured by determining the weight loss upon heating a small sample (e.g., about 1 gram to about 5 grams) of the reaction mixture, to a suitable temperature, e.g., about 125° C., and a time sufficient to remove the liquid therefrom.","Illustrative fatty acids that can be reacted with the polyamine to form the diamidoamine can include, but are not limited to, the alkanoic and alkenoic fatty acids having from about 6 carbon atoms to about 24 carbon atoms, such as lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, oleic acid, linoleic acid, erucic acid, or any combination thereof Mixtures of fatty acids can also be used.","Illustrative fatty acids can be provided or used in the form of crude tall oil (CTO), one or more tall oil distillation products, one or more vegetable oils, and any mixture thereof.","In one embodiment, crude tall oil can be made or produced as an acidified byproduct in the kraft or sulfate processing of wood.","Crude tall oil, prior to refining, can include a mixture of rosin acids, fatty acids, sterols, high-molecular weight alcohols, and other alkyl chain materials.","The components of crude tall oil depend on a variety of factors, such as the particular coniferous species of the wood being processed (wood type), the geographical location of the wood source, the age of the wood, the particular season that the wood is harvested, and others.","Thus, depending on the particular source, crude tall oil can contain about 20 wt % to about 75 wt % of fatty acids (e.g., about 30 wt % to about 60 wt % of fatty acids), about 20 wt % to about 65 wt % of rosin acids and the balance being the neutral and non-saponifiable components.","Crude tall oil can contain at least 10 wt % of neutral materials or non-saponifiable components.","Distillation of crude tall oil can be used to recover a mixture of fatty acids in the C16-C20 range.","Fatty acids found in tall oils can include, but are not limited to, oleic acid, linoleic acid, stearic acid, and palmitic acid.","Rosin acids found in tall oils, include, but are not limited to, abietic acid, dehydroabietic acid, isopimaric acid, and pimaric acid.","Examples of tall oil distillation products that can be used as the fatty acids or at to make up at least a portion of the fatty acids discussed and described herein can include, but are not limited to, tall oil fatty acids (TOFA), distilled tall oil (DTO), tall oil pitch, or any mixture thereof.","The distilled tall oil fraction can have a fatty acids and esters of fatty acids concentration of about 55 wt %, about 60 wt %, or about 65 wt % to about 85 wt %, about 90 wt %, or about 95 wt %.","The distilled tall oil fraction can have a rosin acids or rosins concentration of about 5 wt %, about 10 wt %, or about 15 wt % to about 30 wt %, about 35 wt %, or about 40 wt %.","The distilled tall oil fraction can have a neutrals concentration of about 0.1 wt %, about 1 wt %, or about 1.5 wt % to about 2 wt %, about 3.5 wt %, or about 5 wt %.","The distilled tall oil fraction can have an acid value of about 20, about 25, or about 30 to about 40, about 45, or about 50.The distilled tall oil fraction can have a viscosity (centipoise at 85° C.) of about 10 cP, about 20 cP, about 30 cP, or about 40 cP to about 100 cP, about 120 cP, about 135 cP, or about 150 cP.","The distilled tall oil can have a density of about 840 g/L, about 860 g/L, or about 880 g/L to about 900 g/L, about 920 g/L, or about 935 g/L.","The distilled tall oil fraction can have a saponification number of about 180, about 185, or about 190 to about 200, about 205, or about 210.The distilled tall oil fraction can have an iodine value of about 115, about 117, or about 120 to about 130, about 135, or about 140.The rosin acids derived from crude tall oil are also an intermediate fraction that can be produced from the distillation of crude tall oil.","The tall oil rosin can have a concentration of rosin acids of about 80 wt %, about 85 wt %, or about 90 wt % to about 93 wt %, about 95 wt %, or about 99 wt %.","The tall oil rosin can have a concentration of abietic acid of about 35 wt %, about 40 wt %, or about 43 wt % to about 50 wt %, about 55 wt %, or about 60 wt %.","The tall oil rosin can have a concentration of dehydroabietic acid of about 10 wt %, about 13 wt %, or about 15 wt % to about 20 wt %, about 23 wt %, or about 25 wt %.","The tall oil rosin can have a concentration of isopimaric acid of about 10 wt % or less, about 8 wt % or less, about 5 wt % or less, or about 3 wt % or less.","The tall oil rosin can have a concentration of pimaric acid of about 10 wt % or less, about 8 wt % or less, about 5 wt % or less, or about 3 wt % or less.","The tall oil rosin can have a fatty acids concentration of about 0.5 wt %, about 1 wt %, or about 2 wt % to about 3 wt %, about 5 wt %, or about 10 wt %.","The tall oil rosin can have a concentration of neutral materials of about 0.5 wt %, about 1 wt %, or about 2 wt % to about 3 wt %, about 5 wt %, or about 10 wt %.","The tall oil rosin can have a density of about 960 g/L, about 970 g/L, or about 980 g/L to about 1,000 g/L, about 1,010 g/L, or about 1,020 g/L.","The tall oil rosin can have an acid value of about 150, about 160, or about 165 to about 170, about 175, or about 180.Representative tall oil products can include saturated and unsaturated fatty acids in the C16-C18 range, as well as minor amounts of rosin acids, and can include XTOL® 100, XTOL® 300, and XTOL® 304, XTOL® 520, and LYTOR® 100, all of which are commercially available from Georgia-Pacific Chemicals LLC, Atlanta, Ga. XTOL® 100 includes about 1.6 wt % of palmitic acid, about 2.5 wt % of stearic acid, about 37.9 wt % of oleic acid, about 26.3 wt % of linoleic acid, about 0.3 wt % of linolenic acid, about 2.9 wt % of linoleic isomers, about 0.2 wt % of arachidic acid, about 3.6 wt % eicosatrienoic acid, about 1.4 wt % of pimaric acid, <0.16 wt % of sandarocopimaric, <0.16 wt % of isopimaric acid, <0.16 wt % of dehydroabietic acid, about 0.2 wt % of abietic acid, with the balance being neutrals and high molecular weight species.","LYTOR® 100 includes <0.16 wt % of palmitic acid, <0.16 wt % of stearic acid, about 0.2 wt % of oleic acid, about 0.2 wt % of arachidic acid, about 0.2 wt % eicosatrienoic acid, about 2.2 wt % of pimaric acid, about 0.6 wt % of sandarocopimaric, about 8.5 wt % of palustric acid, about 1.6 wt % of levopimaric acid, about 2.8 wt % of isopimaric acid, about 15.3 wt % of dehydroabietic acid, about 51.4 wt % of abietic acid, about 2.4 wt % of neoabietic acid, with the balance being neutrals and high molecular weight species.","XTOL® 520 DTO includes about 0.2 wt % of palmitic acid, about 3.3 wt % of stearic acid, about 37.9 wt % of oleic acid, about 26.3 wt % of linoleic acid, about 0.3 wt % of linolenic acid, about 2.9 wt % of linoleic isomers, about 0.2 wt % of arachidic acid, about 3.6 wt % eicosatrienoic acid, about 1.4 wt % of pimaric acid, <0.16 wt % wt % of sandarocopimaric, <0.16 wt % of isopimaric acid, <0.16 wt % of dehydroabietic acid, about 0.2 wt % of abietic acid, with the balance being neutrals and high molecular weight species.","Such tall oil products can be used in the reaction with the polyamine or a mixture of polyamines.","Other fatty acids and mixtures of fatty acids, including oxidized and/or dimerized tall oil, such those discussed below can also be employed.","Illustrative vegetable oils that can be used as the fatty acids can include, but are not limited to, safflower oil, grapeseed oil, sunflower oil, walnut oil, soybean oil, cottonseed oil, coconut oil, corn oil, olive oil, palm oil, palm olein, peanut oil, rapeseed oil, canola oil, sesame oil, hazelnut oil, almond oil, beech nut oil, cashew oil, macadamia oil, mongongo nut oil, pecan oil, pine nut oil, pistachio oil, grapefruit seed oil, lemon oil, orange oil, watermelon seed oil, bitter gourd oil, buffalo gourd oil, butternut squash seed oil, egusi seed oil, pumpkin seed oil, borage seed oil, blackcurrant seed oil, evening primrose oil, açaaí oil, black seed oil, flaxseed oil, carob pod oil, amaranth oil, apricot oil, apple seed oil, argan oil, avocado oil, babassu oil, ben oil, borneo tallow nut oil, cape chestnut, algaroba oil, cocoa butter, cocklebur oil, poppyseed oil, cohune oil, coriander seed oil, date seed oil, dika oil, false flax oil, hemp oil, kapok seed oil, kenaf seed oil, lallemantia oil, mafura oil, manila oil, meadowfoam seed oil, mustard oil, okra seed oil, papaya seed oil, perilla seed oil, persimmon seed oil, pequi oil, pili nut oil, pomegranate seed oil, prune kernel oil, quinoa oil, ramtil oil, rice bran oil, royle oil, shea nut oil, sacha inchi oil, sapote oil, seje oil, taramira oil, tea seed oil, thistle oil, tigernut oil, tobacco seed oil, tomato seed oil, wheat germ oil, castor oil, colza oil, flax oil, radish oil, salicornia oil, tung oil, honge oil, jatropha oil, jojoba oil, nahor oil, paradise oil, petroleum nut oil, dammar oil, linseed oil, stillingia oil, vernonia oil, amur cork tree fruit oil, artichoke oil, balanos oil, bladderpod oil, brucea javanica oil, burdock oil, candlenut oil, carrot seed oil, chaulmoogra oil, crambe oil, croton oil, cuphea oil, honesty oil, mango oil, neem oil, oojon oil, rose hip seed oil, rubber seed oil, sea buckthorn oil, sea rocket seed oil, snowball seed oil, tall oil, tamanu oil, tonka bean oil, ucuhuba seed oil, or any mixture thereof.","If the fatty acid includes two or more fatty acids, each fatty acid can be present in the same concentration or different concentrations with respect to one another.","For example, a first fatty acid can be present in a weight ratio of about 99:1, about 90:10, about 80:20, about 70:30, about 60:40, about 50:50, about 40:60, about 30:70, about 20:80, about 10:90, or about 1:99 with respect to another or “second” fatty acid contained therein.","Similarly, if three or more fatty acids are mixed, the three or more fatty acids can be present in any ratio.","The polyamine reacted with the one or more fatty acids to produce the diamidoamine can include, but is not limited to, one or more compounds having the general chemical formal, Formula (II): H2N[(CH2)xNH]yH (II) where x and y can be integers independently selected from 1 to 10.Representative polyamines include the polyethylene polyamines, when x is 2.Of this class of polyalkylene polyamines, specific examples can include, dimethylenetriamine (x=1, y=2), diethylenetriamine (x=2, y=2), triethylenetetramine (x=2, y=3), tripropylenetetramine (x=3, y=3) tetraethylenepentamine (x=2, y=4), and pentaethylenehexamine (x=2, y=5).","The polyamine can be or include a mixture of two or more polyamines.","If the polyamines include two or more polyamines, each polyamine can be present in the same concentration or different concentrations with respect to one another.","For example, a first polyamines can be present in a weight ratio of about 99:1, about 90:10, about 80:20, about 70:30, about 60:40, about 50:50, about 40:60, about 30:70, about 20:80, about 10:90, or about 1:99 with respect to another or “second” polyamine contained therein.","Similarly, if three or more polyamines are mixed, the three or more polyamines can be present in any ratio.","The liquid medium, if present, can be or include water.","The water can be added or generated during the condensation reactions or both.","The liquid medium can also be or include one or more polar aprotic solvents, one or more polar protic solvents, or any combination thereof.","Illustrative polar aprotic solvents can include, but are not limited to, tetrahydrofuran (“THF”), dimethyl sulfoxide (“DMSO”), N-methylpyrrolidone (“NMP”), dimethyl acetamide, acetone, or any combination thereof.","Illustrative polar protic solvents can include, but are not limited to, methanol, ethanol, propanol, butanol, or any combination thereof.","One or more diamidoamines, one or more liquid media, and the saturated dicarboxylic acid and/or the saturated acid anhydride can be mixed to form a triamide reaction mixture.","The diamidoamine, the liquid media, and the saturated dicarboxylic acid and/or saturated acid anhydride can be combined with one another in any order or sequence.","The diamidoamine can be isolated from the diamidoamine reaction mixture and then mixed with the liquid medium and the saturated dicarboxylic acid and/or the saturated acid anhydride to make the triamide reaction mixture.","Or, the liquid medium and the saturated dicarboxylic acid and/or the saturated acid anhydride can be mixed with the diamidoamine reaction mixture to make the triamide reaction for a one pot synthesis.","The molar ratio of the carboxylic acid groups on the saturated dicarboxylic acid to the secondary amine groups on the diamidoamine can be used to favor the reaction product between one saturated dicarboxylic acid molecule and one diamidoamine molecule.","For example, the molar ratio of carboxylic acid groups to secondary amine groups can be about 0.4:1, about 0.5:1, or about 0.7:1 to about 0.9:1, about, 1.0:1, or about 1.2:1.In another example, the molar ratio of the carboxylic acid groups to secondary amine groups can be about 0.4:1 to about 0.6:1, about 0.5:1 to about 0.7:1, about 0.7:1 to about 0.9:1, about 0.8:1 to about 1.1:1, about 0.9:1 to about 1:1, about 0.9:1 to about 1.1:1, or about 0.9:1 to about 1.2:1.The molar ratio of the anhydride group on the saturated acid anhydride to the secondary amine groups on the diamidoamine can be used to favor the reaction product between one saturated acid anhydride molecule and one diamidoamine molecule.","For example, the molar ratio of the anhydride group to the secondary amine groups can be about 0.2:1, about 0.4:1, or about 0.6:1 to about 0.8:1, about 0.9:1, or about 1:1.In another example, the molar ratio of the anhydride group to the secondary amine groups can be about 0.2:1 to about 1:1, about 0.4:1 to about 0.9:1, about 0.75:1 to about 0.85:1, or about 0.78:1 to about 0.82:1.The reaction between the diamidoamine and the saturated dicarboxylic acid or the saturated anhydride can be at a temperature of about 25° C., about 40° C., or about 60° C. to about 130° C. about 150° C. or about 175° C. For example, the reaction temperature can be about 30° C. to about 60° C., about 55° C. to about 85° C., about 60° C. to about 80° C., about 70° C. to about 90° C., about 70° C. to about 80° C., about 73° C. to about 95° C., about 92° C. to about 130° C., about 120° C. to about 160° C., and about 160° C. to about 200° C. Relative to the use of the saturated acid anhydride, the use of the saturated dicarboxylic acid to react the terminal amine groups of the fatty acid amine condensate to terminal carboxylic acid groups often requires higher reaction temperatures.","The reaction time for the reaction between the diamidoamine and the saturated dicarboxylic acid or the saturated anhydride can be about 0.2 hours, about 0.4, or about 0.5 to about 1 hour, about 1.5 hours or about 2 hours.","For example, the reaction time can be about 0.2 hours to about 0.6 hours, about 0.5 hours to about 1 hour, about 0.6 hours to about 0.8 hours, about 0.7 hours to about 1 hour, about 1 hour to about 1.5 hours, about 1 hour to about 1.2 hours, or about 1 hour to about 2 hours.","Relative to the use of a saturated acid anhydride, the use of a saturated dicarboxylic acid to convert the secondary amine groups to the amide groups often requires longer reaction times.","The diamidoamine and the saturated dicarboxylic acid or the saturated anhydride can be reacted until a desired acid value is obtained.","The acid value of the triamide reaction mixture can be about 20 mg of KOH, about 30 mg of KOH, or about 40 mg of KOH to about 80 mg of KOH, about 90 mg of KOH, or about 100 mg of KOH, per gram of triamide reaction mixture.","For example, the triamide reaction mixture can have an acid value of about 25 mg of KOH to about 35 mg of KOH, about 30 mg of KOH to about 50 mg of KOH, about 50 mg of KOH to about 70 mg of KOH, about 55 mg of KOH to about 65 mg of KOH, about 60 mg of KOH to about 90 mg of KOH, about 80 mg of KOH to about 100 mg of KOH, per gram of triamide reaction mixture.","The acid value can be used as a measure of the amount of carboxylic acid groups in the triamide reaction mixture.","The triamide reaction mixture can include a solvent or diluent or “liquid medium.” Suitable liquid mediums can be or include those liquid mediums discussed and described above with reference to the diamidoamine reaction mixture.","The triamide reaction can also be performed neat so the triamide reaction mixture can be free of solvent or liquid medium.","The triamide reaction mixture can have a liquid medium concentration of about 0 wt %, about 1 wt %, or about 3 wt % to about 10 wt %, about 15 wt %, or about 20 wt %, based on the combined weight of the diamidoamine, the liquid medium, and the saturated dicarboxylic acid and/or the saturated acid anhydride.","In another example, the diamidoamine reaction mixture can have a liquid medium concentration of about 0 wt % to about 3 wt %, about 0.1 wt % to about 4 wt %, about 1 wt % to about 6 wt %, about 3 wt % to about 8 wt %, about 7 wt % to about 14 wt %, about 11 wt % to about 17 wt %, or about 12 wt % to about 20 wt %, based on the combined weight of the diamidoamine, the liquid medium, and the saturated dicarboxylic acid and/or the saturated acid anhydride.","During the reaction, the liquid medium can be distilled, evaporated, or otherwise separated from the triamide reaction mixture, which can change the concentration of the liquid medium.","The triamide reaction mixture can have a viscosity of about 55 cP, about 100 cP, or about 150 cP to about 2,000 cP, about 3,000 cP, or about 5,000 cP, at 90° C. For example, the viscosity of the triamide reaction mixture can have a viscosity of about 65 cP to about 105 cP, about 100 cP to about 500 cP, about 400 cP to about 1,000 cP, about 900 cP to about 1,200 cP, about 1,000 cP to about 1,500 cP, about 1,300 cP to about 1,600 cP, about 1,500 cP to about 2,000 cP, about 1,800 cP to about 2,600 cP, about 2,000 cP to about 3,000, about 2,500 cP to about 4,000, about 3,000 cP to about 5,000, at 90° C. The viscosity can be used to characterize the reaction product.","The viscosity can be determined using a Brookfield viscometer.","The viscometer measures the torque required to rotate a spindle at constant speed in a solution of a diamidoamine reaction mixture at 25° C. Standard test methods used for measuring Brookfield viscosity are ASTM D 803-03 and AOCS Ja 10-87 (93).","The triamide reaction mixture can have a solids content of about 80 wt %, about 85 wt %, or about 90 wt % to about 95 wt %, about 98 wt %, or about 100 wt % (e.g., where the solvent- free system has 100 wt % solids), based on the total weight of the triamide reaction mixture.","In another example, the diamidoamine reaction mixture can have a solids content of about 80 wt % to about 85 wt %, about 85 wt % to about 90 wt %, about 90 wt % to about 95 wt %, about 94 wt % to about 98 wt %, about 96 wt % to about 99 wt %, or about 96 wt % to about 100 wt %, based on the total weight of the triamide reaction mixture.","During the reaction, water from the condensation between the diamidoamine and the saturated dicarboxylic acid or the saturated acid anhydride can be distilled from the triamide reaction mixture, which can change the solids content.","Representative saturated dicarboxylic acids can include, but are not limited to, succinic acid, adipic acid, malic acid, and glutaric acid and the like.","Representative saturated acid anhydrides can include, but are not limited to, succinic anhydride, adipic anhydride, and glutaric anhydride.","The triamide can be at least partially isolated from triamide reaction mixture or the triamide reaction mixture can be mixed with the tall oil without further processing.","The triamide and the tall oil can be combined with one another in any order or sequence.","Illustrative tall oils can include, but are not limited to, crude tall oil, distilled tall oil, tall oil bottoms, a dimerized tall oil, a Diels-Alder reaction product and/or an ene reaction product of tall oil with an one or more α,β unsaturated carboxylic acids or acid anhydrides, a Diels-Alder reaction product and/or an ene reaction product of tall oil with an one or more α,β unsaturated carboxylic acids or acid anhydrides that has also been dimerized, or any mixture thereof.","Representative tall oil distillate components include tall oil fatty acids, tall oil rosin acids, and mixtures of these fractions.","As mentioned above, the refinement (e.g., fractionation) of tall oil can, for example, provide C16-C18 saturated and unsaturated fatty acids as well as fatty acid/rosin acid mixtures.","Mixtures of tall oil distillate fractions can also be employed as the tall oil distillate component.","Fatty acid and rosin acid mixtures in any desired ratio can be obtained in a single distillate fraction by adjusting tall oil fractionation conditions.","Representative tall oil distillate components include XTOL® 100, XTOL® 300, and XTOL® 304, XTOL® 520, and LYTOR® 100, all commercially available from Georgia-Pacific Chemicals LLC, Atlanta, Ga.","In one specific embodiment, a mixture of a first tall oil distillate fraction comprising predominantly fatty acids (e.g., XTOL® 100) and a second tall oil distillate fraction comprising predominantly rosin acids (e.g., LYTOR® 100) can be mixed in any proportion.","In such a mixture, representative amounts of fatty acids and rosin acids can be about 45 wt % to about 90 wt % and about 10 wt % to about 55 wt %, respectively.","The mixing ratios of the first tall oil distillate fraction to second tall oil distillate fraction can be in a weight ratio of about 9:1, about 4:1, about 7:3, about 3:2, about 1:1, about 2:3, about 3:7, about 1:4, or about 1:9.Depending on the crude tall oil composition and fractionation conditions, a single tall oil distillate fraction can also suffice to yield a composition that is substantially the same as any of the mixes of tall oil distillate fractions discussed above.","The α,β unsaturated carboxylic acids or acid anhydrides can react with tall oil via the ene reaction or a Diels-Alder reaction on the tall oil fatty acids and/or the rosin acids in the tall oil.","The modified tall oil product generated from the reaction of tall oil with the specific α,β unsaturated anhydride, maleic anhydride, can be referred to as a “maleated tall oil,” which includes “maleated fatty acids” and “maleated rosin acids.” Non-limiting examples of representative reactions that can occur can include those discussed and described in U.S. Pat.","Nos.",": 4,927,669; 8,133,970; and 8,334,363.The ene reaction and the Diels-Alder reaction are explained in further detail in Jerry March & Michael B. Smith, MARCH'S ADVANCED ORGANIC CHEMISTRY: REACTIONS, MECHANISMS, AND STRUCTURE (7th ed.","John Wiley & Sons Inc. 2013) (1985).","The amount of α,β unsaturated carboxylic acid or acid anhydride reacted with the tall oil can vary based, at least in part, on the specific tall oil product to be reacted.","Suitable amounts of the carboxylic acid and/or acid anhydride reacted with the tall oil can be about 1 wt %, about 2 wt %, about 3 wt %, about 5 wt %, about 10 wt %, or about 15 wt % to about 30 wt %, about 35 wt %, about 40 wt %, about 45 wt %, or about 50 wt %, based on the combined weight of the tall oil and the carboxylic acid and/or acid anhydride the desired amount of the Diels-Alder product and/or the ene product.","The tall oil can have the tall oil substituted with the α,β unsaturated carboxylic acids or acid anhydrides in an amount of about 1 wt %, about 3 wt %, or about 5 wt % to about 20 wt %, about 25 wt %, or about 30 wt %, based on the total weight of tall oil.","For example, the tall oil can have the tall oil substituted with the α,β unsaturated carboxylic acids or acid anhydrides in an amount of about 2 wt % to about 7 wt %, about 5 wt % to about 10 wt %, about 10 wt % to about 20 wt %, about 18 wt % to about 22 wt %, about 20 wt % to about 27 wt %, based on the total weight of tall oil.","The reaction of tall oil and the α,β unsaturated carboxylic acids or acid anhydrides, can be performed at a reaction temperature of about 150° C. to about 250° C., about 200° C. to about 230° C., or about 215° C. to about 225° C. The reaction can be quenched after a reaction time of about 12 hours, about 16 hours, about 20 hours, about 22 hours, about 26 hours, about 30 hours, about 34 hours, about 38 hours, or greater.","For example, the reaction time can be about 12 hours to about 36 hours or about 20 hours to about 30 hours.","The dimerized tall oil can be obtained by catalytic dimerization of the tall oil fatty acids or by the oxidation of tall oil to provide an ether bond linking the fatty acid's hydrocarbon chain.","In an embodiment, the catalytic dimerization can be clay catalyzed Diels-Alder type reaction that links at least two hydrocarbon chains of the tall oil fatty acids through a carbon-carbon bond.","In another embodiment, tall oil can be oxidized by heating the tall oil material to a temperature of at least 150° C. For example, the tall oil can be heated to a temperature of about 155° C., about 160° C., or about 165° C. to about 170° C., about 180° C., about 190° C., about 200° C., or about 225° C., in the presence of an oxidant.","In at least one specific example, the tall oil can be heated to a temperature of about 160° C. to about 170° C., followed by contacting the heated tall oil composition with oxygen or air.","For example, the tall oil can be heated to a temperature of about 160° C. to about 170° C., followed by sparging oxygen or air through the heated tall oil composition.","As understood by those skilled in the art, a variety of techniques and devices can advantageously be used to contact the heated tall oil with the oxygen or air and the present method is not limited to any specific technique or equipment.","The hydrocarbon chains can be fatty acids and rosin acids.","The hydrocarbon chains can be, for example, C6-C22 fatty acids.","The hydrocarbon chains can be, for example, C16-C22 fatty acids.","The hydrocarbon chains can be, for example, C16-C18 fatty acids.","The hydrocarbon chains can be, for example, a C18 fatty acid.","The hydrocarbon chains can be, for example, oleic acid, linoleic acid, and linolenic acid.","Illustrative Diels-Alder reaction product and/or an ene reaction product of tall oil with an one or more α,β unsaturated carboxylic acids or acid anhydrides and illustrative Diels-Alder reaction product and/or an ene reaction product of tall oil with one or more α,β unsaturated carboxylic acids or acid anhydrides that has also been dimerized can include those compositions discussed and described in U.S. Patent Application Publication Nos.","2008/0179570, 2008/0194795, 2009/0065736, and 2009/0194731.The emulsifier can be neutralized (e.g., converted to its corresponding alkali or alkaline earth metal salt) before spray drying.","The emulsifier used to form the spray dried emulsifier, namely the triamide and the tall oil, is acidic prior to neutralization.","In the case of the triamide, acidity results from the installation of a carboxylic acid group from the condensation reaction of the diamidoamine to the saturated dicarboxylic acid and/or acid anhydride.","In the case of the tall oil, acidity also results from the addition of the unsaturated dicarboxylic acid and/or unsaturated acid anhydride functionality (e.g., in the Diels-Alder reaction or the ene reaction with tall oil fatty acids and/or tall oil rosin acids).","These acidic components can be neutralized (or saponified) by the addition of a suitable base.","Neutralization with an alkali metal hydroxide, an alkaline earth metal hydroxide, an alkali metal oxide, an alkaline earth metal oxide, or any mixture of these bases can result in the conversion of the triamide and the tall oil to their corresponding alkali metal salts and/or alkaline earth metal salts (e.g., carboxylate salts).","For example, the carboxylic acid of the triamide can be reacted with any of these bases to form metal carboxylate groups (e.g., sodium carboxylate groups).","Suitable bases within the classes given above include the hydroxides and oxides of lithium, sodium, potassium, and calcium.","Compared to the oxides, the hydroxides of these metals can provide a faster and more efficient neutralization.","Bases can be added in either a solid form or as a solution, e.g., an aqueous solution.","Representative aqueous solutions can include, but are not limited to, about 25 wt % to about 75 wt % of sodium hydroxide or calcium hydroxide.","Mixtures of the above bases can also be used via a simultaneous neutralization reaction, although sequential reaction using different bases in series can also be employed.","The amount of base required for neutralization the emulsifier can be determined from a stoichiometric determination or otherwise from direct analysis/monitoring of the acid value prior to and/or during neutralization.","The acid value (in mg KOH/g required for neutralization) can be measured, for example, using ASTM D1980-87.The base can be added gradually over a period of time of about 10 minutes to about 2 hours to reduce or avoid significant temperature deviations due to the heat release upon neutralization.","Gradual addition is also suitable in view of the low initial aqueous solubility of the triamide and/or the tall oil, prior to saponification.","The acid value of the neutralized emulsifier can be about 0 mg of KOH, about 1 mg of KOH, or about 2 mg of KOH to about 8 mg of KOH, about 10 mg of KOH, or about 12 mg of, per gram of emulsifier.","For example, the emulsifier can have an acid value of about 0 mg of KOH to about 2 mg of KOH, about 1 mg of KOH to about 3 mg of KOH, about 1 mg of KOH to about 5 mg of KOH, about 2 mg of KOH to about 8 mg of KOH, about 9 mg of KOH to about 12 mg of KOH, per gram of emulsifier.","The neutralized emulsifier can have a pH of about 7, about 8, about 9, about 10, about 11, or about 11.5.For example, the neutralized emulsifier can have a pH of about 7.5 to about 8.5, about 8 to about 10, about 9 to about 11, about 9 to about 11.5, or about 8 to about 9.5.Neutralization with a base can be carried out at a temperature of about 50° C., about 55° C., or about 60° C. to about 85° C., about 90° C., or about 100° C. For example, neutralization can be performed at a temperature of about 60° C. to about 80, about 60° C., about 60° C. to about 75° C., about 65° C. to about 80° C., or about 75° C. to about 100° C. The emulsifier can be spray dried to produce a spray dried emulsifier.","An aqueous diluent can be added to the emulsifier to adjust the viscosity and the solids content.","Prior to spray drying, the solids content of the emulsifier can be adjusted to about 35 wt %, about 40 wt %, about 45 wt %, about 50 wt %, or greater, based on the weight of the emulsifier.","For example, the solids content of the emulsifier can be about 35 wt % to about 45 wt %, about 40 wt % to about 50 wt %, about 45 wt % to about 50 wt %, based on the weight of the emulsifier prior to spray drying.","In some embodiments, sufficient water can be added with the base during neutralization to achieve the desired solids content.","The emulsifier can be fed to the spray drier head, which can be heated (e.g., using natural gas) to provide a spray drier inlet temperature of about 160° C. to about 250° C. The inlet temperature (or simply the “spray drying temperature”) can be about 180° C. to about 225° C., where higher temperatures directionally allow for higher throughput of the aqueous composition to be spray dried.","Spray drying involves atomization, using an appropriate rotary or nozzle atomizer, of this aqueous composition.","Rotary atomization, for example, can often carried out by contacting the solution with a wheel rotating at 30,000-50,000 rpm to produce the required spray.","Upon contact of the spray with hot air in the spray dryer chamber, the moisture can be quickly evaporated into an exhaust stream.","The resulting solid, free flowing particles of the spray dried emulsifier discharged continuously from the bottom of the conical chamber.","The outlet temperature of the spray drier can be about 75° C. to about 100° C. Representative spray dryers include those supplied by Niro, A/S (Soeborg, Denmark).","The spray dried emulsifier can have small particle sizes, which can provide dispersion and solubilization of the spray dried emulsifier in drilling fluids.","The particle size populations can fit a normal distribution with an average cross-sectional length or average particle size (e.g., average diameter for spherical particles) of less than 120 μm, less than 100 μm, or less than 80 μm.","The average particle size of the particles can be about 10 about 20 μm, or about 30 μm to about 90 μm, about 100 μm, or about 150 μm.","For example, the average particle size can be about 10 μm to about 30 μm, about 20 μm to about 50 μm, about 30 μm to about 75 μm, about 70 μm to about 100 μm, about 65 μm to about 85 μm, about 80 μm to about 120 μm, or about 100 μm to about 1,500 μm.","In another example, at least 50 wt %, at least 60 wt %, at least 70 wt %, at least 80 wt %, or at least 90 wt % of emulsifier particles can have a particle size of less than 80 microns, based on the total weight of the spray dried emulsifier.","The average cross-sectional length or average particle size of the particles can be measured with a light scattering particle size distribution analyzer, such as those manufactured by Horiba Instruments, Inc. (Irvine, Calif.).","The spray dried emulsifier can have a bulk density of about 0.2 g/mL, about 0.3 g/mL, or about 0.4 g/mL to about 0.6 g/mL, about 0.7 g/mL, or about 0.8 g/mL.","For example, the bulk density of the spray dried emulsifier can be about 0.2 g/mL to about 0.35 g/mL, about 0.24 g/mL to about 0.56 g/mL, about 0.3 g/mL to about 0.5 g/mL, about 0.4 g/mL to about 0.48 g/mL, or about 0.40 g/mL, to about 0.66 g/mL.","The spray dried emulsifier can have a residual moisture content of less than 10 wt %, less than 7 wt %, less than 5 wt %, less than 3 wt %, or less than 1 wt %, based on the total weight of the spray dried emulsifier.","For example, the spray dried emulsifier can have a residual moisture content of about 0.5 wt % to about 3 wt %, about 1 wt % to about 3 wt %, about 2 wt % to about 5 wt %, or about 3 wt % to about 7 wt %, based on the total weight of the spray dried emulsifier.","Silica or other anti-caking or anti-clumping agents can be added to the powder.","For example, one or more anti-caking or anti-clumping agents can be added to the spray dried emulsifier in an amount of about 0.1 wt %, about 0.2 wt %, about 0.3 wt %, or about 0.5 wt % to about 1 wt %, about 1.5 wt %, about 2 wt %, or about 3 wt %, based on the combined weight or spray dried emulsifier and the anti-clumping agent.","Otherwise, additional drying can be used.","The spray dried product can be free flowing and can be stored for extended periods in the absence of exposure to moisture (e.g., in vapor barrier bags) without “re-massing” or significant agglomeration of the solid particles.","This is based on oven aging studies of the spray dried emulsifier, used to simulate extended storage at high ambient temperatures.","The addition of water to the spray dried emulsifier will can produce or form a basic mixture, having a pH of about 8 to about 11.The drilling fluids can be prepared by mixing the spray dried emulsifier, a continuous oil-based phase (e.g., maleated tall oil), and a dispersed aqueous phase (e.g., water or an aqueous brine solution).","The spray dried emulsifier, the continuous oil-based phase, and the dispersed aqueous phase of the drilling fluid can be mixed or otherwise combined in any order.","For example, the spray dried emulsifier can be first dissolved in either the oil phase or the aqueous phase, and the aqueous phase can then be gradually added to the oil phase with vigorous mixing.","The converse method (e.g., addition of the oil phase to the aqueous phase) or alternate addition of the two phases can likewise be employed.","The drilling fluid can be subjected to high shear condition to provide an emulsion.","Any of a wide variety of slow or high speed mixers or agitators, homogenizers, or colloid mills can be used to obtain the degree of contact between the phases, required to disperse the internal aqueous phase in the external oil phase.","The amount of emulsifier required to produce a stable emulsion in any given application will depend on the relative proportions of the oil and aqueous phases as well as upon the chemical nature of the respective phases and the particular manner in which the emulsion is prepared.","The drilling fluid can include the spray dried emulsifier at a concentration of about 0.2 wt %, about 0.5 wt %, about 1 wt %, about 2 wt %, about 3 wt %, about 4 wt %, about 5 wt %, about 6 wt %, about 7 wt %, about 8 wt %, about 9 wt %, about 10 wt %, or greater, based on the combined weight of the spray dried emulsifier, the oil phase, and the aqueous phase.","For example, the drilling fluid can include the spray dried emulsifier at a concentration of about 0.2 wt % to about 1 wt %, about 0.5 wt % to about 1.5 wt %, about 1 wt % to about 3 wt %, about 2 wt % to about 5 wt %, or about 1 wt % to about 6 wt %, based on the combined weight of the spray dried emulsifier, the oil phase, and the aqueous phase.","The drilling fluid can have an aqueous phase concentration of about 5 wt %, about 10 wt %, about 15 wt %, about 20 wt %, about 25 wt %, about 30 wt %, about 35 wt %, or about 40 wt %, based on the combined weight of the spray dried emulsifier, the oil phase, and the aqueous phase.","For example, the drilling fluid can have an aqueous phase concentration of about 5 wt % to about 10 wt %, about 10 wt % to about 20 wt %, about 20 wt % to about 30 wt %, about 30 wt % to about 40 wt %, about 5 wt % to about 40 wt %, about 5 wt % to about 30 wt %, about 5 wt % to about 20 wt %, about 10 wt % to about 40 wt %, or about 10 wt % to about 30 wt %, based on the combined weight of the spray dried emulsifier, the oil phase, and the aqueous phase.","The drilling fluid can have an aqueous phase concentration of about 40 wt %, about 45 wt %, about 50 wt %, about 54 wt %, about 55 wt %, about 60 wt %, about 65 wt %, about 70 wt %, about 75 wt %, about 80 wt %, about 85 wt %, about 95 wt %, based on the combined weight of the spray dried emulsifier, the oil phase, and the aqueous phase.","For example, the drilling fluid can have an aqueous phase concentration of about 54 wt % to about 60 wt %, about 55 wt % to about 70 wt %, about 65 wt % to about 85 wt %, or about 80 wt % to about 95 wt %, based on the combined weight of the spray dried emulsifier, the oil phase, and the aqueous phase.","The spray dried emulsifier can be compatible with any of a number of oil bases typically used in invert emulsions, including diesel oil and other hydrocarbons, such as C14-C20 paraffins, iso-paraffins, olefins, iso-olefins, aromatics, naphthalenes, and other hydrocarbon mixtures including various products of crude oil refining.","For the aqueous phase, a brine solution is often used, with representative brine solutions containing sodium chloride, potassium chloride, magnesium chloride, calcium chloride, or any mixtures of these in amounts up to saturation of the aqueous phase.","Salt concentrations can be about 20 wt % to about 35 wt % of the aqueous phase.","Dissolved salts in the aqueous phase can be used, for example, to increase drilling fluid density, decrease swelling effects of aqueous matter on formation clays, and/or reduce hole enlargement caused by the dissolution of water soluble formation components.","When the emulsion is to contain suspended solids (e.g., a clay) or other additives, these can be added after the emulsion is prepared under high shear conditions, rather than to one phase or the other.","Additives can be introduced simultaneously or sequentially, and accompanied by continuous mixing or agitation.","For example, a weighting material which increases the density of the drilling fluid can be added.","The weighting agent can be any of the high density materials conventionally employed (e.g., barites, whiting, or calcined clay) to achieve a desired density (e.g., about 1.05 g/ml to about 2 g/ml or about 65 lbs/ft3 to about 125 lbs/ft3).","Other solid additives can include organoclays, e.g., organophilic clays, that can help suspend drill cuttings.","One particular commercial organophilic clay that can be used can be or include the organophilic clay sold under the name VG-Plus sold by M-I Swaco, LLC.","Fluid loss additives, which can serve to increase viscosity and/or reduce the escape of the fluid into permeable formations traversed by the well bore, can be incorporated into the invert emulsion.","The amount added should not increase the viscosity of the composition to such an extent that efficient pumping of the drilling fluid is compromised.","The fluid loss component additive can be or include a hydratable clay or clay-like material, although asphalt, carbon black, or any conventional additive can be used.","High quality clays such as bentonite, montmorillonite, and kaolinite are often employed.","Other conventional additives, including filter loss agents, other viscosifiers, wetting agents, stabilizers, gel strength, and/or rheological control agents can be incorporated into the invert emulsion drilling fluid.","EXAMPLES In order to provide a better understanding of the foregoing discussion, the following non-limiting examples are offered.","Although the examples can be directed to specific embodiments, they are not to be viewed as limiting the invention in any specific respect.","Synthesis of Emulsifier C1 A condenser and a Barrett trap were attached to a reaction vessel.","To the reaction vessel was added 1,656.2 g of XTOL® 100 (available from Georgia-Pacific Chemicals LLC).","The XTOL® 100 was heated to 90° C. under nitrogen for 1 hour.","To the XTOL® 100 was slowly added 303.4 g of diethylenetriamine, 7.3 g of triethylenetetramine, and 7.3 g tetraethylenepentamine to form a reaction mixture.","The reaction mixture was heated to 160° C. for 4 hours.","From the reaction mixture 97 g of distillate was collected in the Barrett trap.","The reaction mixture was cooled to 66° C. and 225.9 g maleic anhydride was added in small quantity additions.","The temperature of the reaction mixture increased to approximately 85° C. over 105 minutes.","The triamide reaction product was obtained in a 93% yield with a final acid value of 61.4 mg KOH/gram of sample, and a total amine value of 20.5 mg KOH/gram of sample.","The triamide was a waxy, brown solid, which had a Brookfield viscosity of 75 cP at 140° C. The triamide was then mixed with a modified tall oil product in a ratio of 67 wt % modified tall oil product to 33 wt % of the triamide.","The modified tall oil product was a reaction product of tall oil and maleic anhydride, which yielded a 12 wt % maleation.","The tall oil for the maleation was 69 wt % of tall oil fatty acids and 31 wt % of rosin acids, based on the combined weight of the tall oil fatty acids and the rosin acids.","The mixture of the triamide and modified tall oil product had an acid value of 198.6 mg KOH/gram of sample and a total amine value of 3.5 mg KOH/gram of sample.","The mixture of the triamide and modified tall oil product was then heated to 90° C. and neutralized by slowly adding to a pre-mixed solution of 250 grams of tap water and 70.8 grams of 50% sodium hydroxide solution.","The final acid number of the neutralized product was adjusted to 0.5 mg KOH/gram of solution with a solids content of 48.9% and a final pH of 11.3.The mixture was adjusted to 21.3 wt % solids, and spray dried on a Niro laboratory spray dryer.","Synthesis of Emulsifier Ex.","1 A condenser and a Barrett trap were attached to a reaction vessel.","To the reaction vessel was added 839 g of XTOL® 100 (available from Georgia-Pacific Chemicals LLC).","The XTOL® 100 was heated to 90° C. under nitrogen for 1 hour.","To the XTOL® 100 was slowly added 153.7 g of diethylenetriamine, 3.7 g of triethylenetetramine, and 3.7 g tetraethylenepentamine to form a reaction mixture.","The reaction mixture was heated to 160° C. for 3 hours.","From the reaction mixture, 47.1 g of distillate was collected in the Barrett trap.","The reaction mixture was cooled to 85° C. and decanted.","The isolated amidoamine had a final acid value of 9.9 mg KOH/ gram of sample and a total amine value of 106.4 mg KOH/gram of sample.","To 188.4 g of the isolated reaction mixture was added 22 g of succinic anhydride.","The reaction mixture was heated at 120° C. for 2 hours.","The triamide reaction product was a waxy, brown solid obtained in a 93% yield with a final acid value of 51.3 mg KOH/gram of sample and a total amine value of 37.6 mg KOH/gram of sample.","The triamide was then mixed with a modified tall oil product in a ratio of 67 wt % modified tall oil product to 33 wt % of the triamide.","The modified tall oil product was a reaction product of tall oil and maleic anhydride, which yielded a 12 wt % maleation.","The tall oil for the maleation was 69 wt % of tall oil fatty acids and 31 wt % of rosin acids, based on the combined weight of the tall oil fatty acids and the rosin acids.","The mixture of the triamide and modified tall oil product had an acid value of 168.8 mg KOH/gram of sample and a total amine value of 9.9 mg KOH/gram of sample.","The mixture of the triamide and modified tall oil product was then heated to 90° C. and neutralized by slowly adding to a pre-mixed solution of 150 grams of tap water and 36.1 grams of 50% sodium hydroxide solution.","The final acid number of the neutralized product was adjusted to 0.6 mg KOH/gram of solution and a solids content of 50 wt %.","This solution was then spray dried on a Niro laboratory spray dryer.","Drilling Fluids for Emulsifiers C1 and Ex.","1 Comparative and inventive drilling fluids were made.","The drilling fluids were prepared by combining the ingredients in a Hamilton Beach mixer and then shearing the composition for 5 minutes at 6,000 rpm in a Silverson shear mixer.","The compositions for the comparative drilling fluid and the inventive drilling fluid are shown in Table 1.TABLE 1 Drilling Fluids Comparative Drilling Inventive Drilling Mix time after Fluid Fluid addition #2 Diesel 180.5 g 180.5 g VG-Plus 6 g 6 g 10 minutes Lime 2 g 2 g 5 minutes Emulsifier C1 5 g 0 g Emulsifier Ex.","1 0 g 5 g 25 wt % CaCl2 (aq) 71.5 g 71.5 g 10 minutes Barite 281 g 281 g 5 minutes Both the comparative drilling fluid and the inventive drilling fluid were of the same compositions except for the triamide used.","The comparative drilling fluid used comparative emulsifier (C1).","The comparative emulsifier was a spray dried mixture of tall oil and a triamide of Formula (I) except R4 was a C2-alkylene diyl group (e.g., ethylene group).","The inventive drilling fluid used emulsifier (Ex.","1), which was a spray dried mixture of tall oil and triamide of Formula (I) where R4 was a C2-alkenylene diyl group (e.g., ethylene diyl group).","The before hot roll (BHR) rheology, plastic viscosity, yield point, electrical stability, and gel strengths for the comparative and inventive drilling fluids were measured.","Then, the drilling fluids were hot rolled for 16 hours at 150° F. and the after hot roll (AHR) rheology, plastic viscosity (PV), yield point (YP), electrical stability (ES), ten second gel strength (10″), and ten minute gel strength (10′) were measured.","The inventive drilling fluid was tested twice.","Table 2 shows the results for the rheology tests.","TABLE 2 Rheology Properties Comparative Inventive Inventive Drilling Drilling Fluid Drilling Fluid Fluid (Test 1) (Test 2) AHR AHR AHR AHR AHR AHR Rheology BHR 40° F. 150° F. BHR 40° F. 150° F. BHR 40° F. 150° F. 600 rpm 50 170 57 54 158 53 50 158 52 300 rpm 30 102 35 33 93 31 29 92 28 200 rpm 23 79 27 25 70 23 21 68 21 100 rpm 16 52 20 18 45 15 15 43 14 6 rpm 8 21 10 9 15 7 7 18 6 3 rpm 7 19 10 8 13 6 6 12 6 PV 20 68 22 21 65 22 21 66 24 YP 10 34 13 12 28 9 8 26 4 10″ Gel 9 22 11 10 16 8 7 16 7 10′ Gel 13 33 15 16 26 15 10 21 10 All testing on oil-based drilling fluids was conducted according to the API Recommended Practice Standard 13B-2, Third Edition, February 1998.The rheology data given in Table 2 indicates that the inventive drilling fluids (Tests 1 and 2) show a lower rheological profile at lower rpms (e.g., about 3 rpm to about 6 rpm), lower yield points, and lower gel strengths for the inventive fluids as compared to the comparative drilling fluid.","The electric stability test is an indication of the quality of the invert emulsion.","Table 3 shows the results of the electrical stability test.","TABLE 3 Electrical stability Inventive Inventive Comparative Drilling Drilling Drilling Fluid Fluid Fluid (Test 1) (Test 2) AHR AHR AHR BHR 150° F. BHR 150° F. BHR 150° F. ES (Volts at 752 1141 837 1018 701 894 150° F.) The electrical stability of the inventive fluids showed similar values before hot roll (BHR) and equivalent or slightly lower electrical stability after hot roll (AHR).","The high temperature/high pressure fluid loss tests were conducted with a 500 psi differential pressure between the top and the bottom of the HTHP cell.","The HTHP fluid loss test was performed after hot rolling at a 150° F. The HTHP fluid loss testing was performed at 250° F. As shown in Table 4, the results of the high temperature/high pressure fluid loss testing indicate that the inventive fluids (Tests 1 and 2) have lower fluid loss versus the comparative fluid.","These results indicate that the inventive fluids have a lower loss of fluid to the formation, which is highly desirable especially when drilling in sensitive formations.","TABLE 4 High Temperature/High Pressure and Water Loss Comparative Inventive Drilling Inventive Drilling Drilling Fluid Fluid (Test 1) Fluid (Test 2) AHR 150° F. AHR 150° F. AHR 150° F. HT/HP at 8.2 6.0 6.0 250° F. (mL) Water Loss 0 0 0 (mL) Comparative and inventive drilling fluids were made under contaminated conditions using API Standard Evaluation Clay (API Clay) (See Table 5).","TABLE 5 Drilling Fluids With API Clay Comparative Drilling Inventive Drilling Mix time after Fluid Fluid addition #2 Diesel 180.5 g 180.5 g VG-Plus 6 g 6 g 10 minutes Lime 2 g 2 g 5 minutes Emulsifier C1 5 g 0 g Emulsifier Ex.","1 0 g 5 g 25 wt % CaCl2 (aq) 71.5 g 71.5 g 10 minutes Barite 281 g 281 g 5 minutes API Clay 20 g 20 g 5 minutes The results of the contamination studies using the API Standard Evaluation Clay are shown in Table 6.The inventive drilling fluid is very effective at maintaining low end (e.g., about 3 rpm to about 6 rpm) rheology while maintaining yield point and gel strengths in the presence of API grade bentonite clay.","TABLE 6 Rheology Properties With API Clay Comparative Inventive Inventive Drilling Drilling Fluid Drilling Fluid Fluid (Test 1) (Test 2) AHR AHR AHR AHR AHR AHR Rheology BHR 40° F. 150° F. BHR 40° F. 150° F. BHR 40° F. 150° F. 600 rpm 58 189 59 65 195 64 57 195 62 300 rpm 36 110 34 42 113 38 35 114 36 200 rpm 30 83 28 35 85 30 29 86 28 100 rpm 22 53 20 26 54 21 22 55 19 6 rpm 12 18 10 15 18 10 12 18 9 3 rpm 12 15 9 13 15 9 11 15 8 PV 22 79 25 23 82 26 22 81 26 YP 14 31 9 19 31 12 13 33 10 10″ Gel 14 18 10 15 18 12 13 18 10 10′ Gel 18 25 15 21 25 17 15 27 16 Table 7 shows the electric stability tests for the comparative and inventive drilling fluids in the presence of clay.","TABLE 7 Electrical Stability With API Clay Inventive Inventive Comparative Drilling Drilling Drilling Fluid Fluid Fluid (Test 1) (Test 2) AHR AHR AHR BHR 150° F. BHR 150° F. BHR 150° F. ES (Volts at 375 588 448 608 572 735 150° F.) The electrical stability of the inventive fluids showed similar values before hot roll (BHR) and slightly higher electrical stability values after hot roll (AHR).","Table 8 shows the results of the high temperature/high pressure fluid loss testing indicate that the inventive fluids (Tests 1 and 2) have lower fluid loss versus the comparative fluid in the presence of API grade bentonite clay.","TABLE 8 High Temperature/High Pressure and Water Loss With API Clay Comparative Inventive Drilling Inventive Drilling Drilling Fluid Fluid (Test 1) Fluid (Test 2) AHR 150° F. AHR 150° F. AHR 150° F. HT/HP at 12.0 7.6 6.6 250° F. Water Loss 0 0 0 Synthesis of Emulsifier C2 A condenser and a Barrett trap were attached to a reaction vessel.","To the reaction vessel was added 662.1 g of coconut oil.","The coconut oil was heated to 90° C. under nitrogen for 1 hour.","To the coconut oil was slowly added 203.6 g of diethylenetriamine to form a reaction mixture.","The temperature of the reaction mixture was increased to approximately 120° C. over approximately 30 minutes.","The reaction mixture was heated to 130° C. for 4 hours and to 160° C. for an additional 4 hours.","The reaction mixture was the cooled to 85° C. and decanted.","The isolated amidoamine had a final acid value of 9.9 mg KOH/ gram of sample and a total amine value of 106.4 mg KOH/gram of sample.","To 326.1 g of the isolated reaction mixture was added 44 g of maleic anhydride slowly, and the reaction mixture was heated to 70° C. The temperature was increased to approximately 80° C. over approximately 30 minutes.","The triamide reaction product was a waxy, brown solid obtained in a 93% yield, and having a final acid value of 70.6 mg KOH/gram of sample and a total amine value of 18.8 mg KOH/gram of sample.","The triamide was then mixed with a modified tall oil product in a ratio of 67 wt % modified tall oil product to 33 wt % of the triamide.","The modified tall oil product was a reaction product of tall oil and maleic anhydride, which yielded a 12 wt % maleation.","The tall oil for the maleation was 69 wt % of tall oil fatty acids and 31 wt % of rosin acids, based on the combined weight of the tall oil fatty acids and the rosin acids.","The mixture of the triamide and modified tall oil product had an acid value of 202.1 mg KOH/gram of sample and a total amine value of 5.1 mg KOH/gram of sample.","The mixture of the triamide and modified tall oil product was then heated to 90° C. and neutralized by slowly adding a solution of 200 grams of tap water and 57.7 grams of 50% sodium hydroxide solution.","The final acid number of the neutralized product was adjusted to 0.8 mg KOH/gram of solution and a solids content of 49.1 wt %.","This solution was then spray dried on a Niro laboratory spray dryer.","Synthesis of Emulsifier Ex.","2 The amidoamine product of the inventive emulsifier was made identically as describe above for emulsifier C2.To 348.1 g of the isolated reaction mixture was added 54.7 g of succinic anhydride.","The reaction mixture was heated to 130° C. for 2 hours then to 140° C. for 2 hours.","The triamide reaction product was a waxy, brown solid obtained in a 93% yield with a final acid value of 42.8 mg KOH/gram of sample and a total amine value of 17.5 mg KOH/gram of sample.","The triamide was then mixed with a modified tall oil product in a ratio of 67 wt % modified tall oil product to 33 wt % of the triamide.","The modified tall oil product was a reaction product of tall oil and maleic anhydride, which yielded a 12 wt % maleation.","The tall oil for the maleation was 69 wt % of tall oil fatty acids and 31 wt % of rosin acids, based on the combined weight of the tall oil fatty acids and the rosin acids.","The mixture of the triamide and modified tall oil product was then heated to 90° C. and neutralized by slowly adding a solution of 200 grams of tap water and 57.7 grams of 50% sodium hydroxide solution.","The mixture of the triamide and modified tall oil product had an acid value of 188 mg KOH/gram of sample and a total amine value of 5.1 mg KOH/gram of sample.","Drilling Fluids for Emulsifiers C2 and Ex.","2 Comparative and inventive drilling fluids were made with using the emulsifiers containing coconut oil.","The drilling fluids were prepared by combining the ingredients in a Hamilton Beach mixer and then shearing the composition for 5 minutes at 6,000 rpm in a Silverson shear mixer.","The compositions for the comparative drilling fluid and the inventive drilling fluid are shown in Table 9.TABLE 9 Drilling Fluids Comparative Drilling Inventive Drilling Mix time after Fluid Fluid addition #2 Diesel 180.5 g 180.5 g VG-Plus 6 g 6 g 10 minutes Lime 2 g 2 g 5 minutes Emulsifier C2 5 g 0 g Emulsifier Ex.","2 0 g 5 g 25 wt % CaCl2 (aq) 71.5 g 71.5 g 10 minutes Barite 281 g 281 g 5 minutes Both the comparative drilling fluid and the inventive drilling fluid were of the same compositions except for the triamide used in the emulsifier.","The comparative drilling fluid used comparative emulsifier (C2).","The comparative emulsifier was a mixture of tall oil and a triamide of Formula (I) except R4 was a C2-alkylene diyl group (e.g., ethylene group).","The inventive drilling fluid used emulsifier (Ex.","2), which was a spray dried mixture of tall oil and triamide of Formula (I) where R4 was a C2-alkenylene diyl group (e.g., ethylene diyl group).","The before hot roll rheology, plastic viscosity, yield point, electrical stability, and gel strengths for the comparative and inventive drilling fluids were measured.","The drilling fluids were then hot rolled for 16 hours at 40° F. and 150° F. and the after hot roll rheology, plastic viscosity, yield point, electrical stability, ten second minute gel strengths, and ten minute gel strength were measured.","Table 10 shows the results for the rheology tests.","TABLE 10 Rheology Properties Comparative Inventive Drilling Fluid Drilling Fluid AHR AHR AHR AHR Rheology BHR 40° F. 150° F. BHR 40° F. 150° F. 600 rpm 65 177 67 60 164 58 300 rpm 45 110 44 40 96 35 200 rpm 37 84 37 32 72 28 100 rpm 29 56 28 24 46 20 6 rpm 18 20 17 13 15 10 3 rpm 7 18 17 12 13 9 PV 20 67 23 20 68 23 YP 25 43 21 20 28 12 10″ Gel 17 21 16 12 15 12 10′ Gel 20 29 21 14 19 14 Table 11 shows the results of the electrical stability test.","TABLE 11 Electrical Stability Comparative Drilling Fluid Inventive Drilling Fluid BHR AHR 150° F. BHR AHR 150° F. ES (Volts at 857 1160 800 1051 150° F.) Table 12 shows the results for the high temperature/high pressure water loss test for the comparative drilling fluid using C2 and the inventive drilling fluid using Ex 2.TABLE 12 High Temperature/High Pressure and Water Loss Comparative Drilling Fluid Inventive Drilling Fluid AHR 250° F. C AHR 150° F. HT/HP at 9.4 8.6 250° F. Water 0 0 Loss Comparative and inventive drilling fluids were made again with the addition of API grade bentonite clay.","The compositions are shown in Table 13.TABLE 13 Drilling Fluids With API Clay Comparative Inventive Mix time Drilling Fluid Drilling Fluid after addition #2 Diesel 180.5 g 180.5 g VG-Plus 6 g 6 g 10 minutes Lime 2 g 2 g 5 minutes Emulsifier C2 5 g 0 g Emulsifier Ex.","2 0 g 5 g 25 wt % CaCl2 (aq) 71.5 g 71.5 g 10 minutes Barite 281 g 281 g 5 minutes API Clay 20 g 20 g 5 minutes The before hot roll rheology, plastic viscosity, yield point, electrical stability, and gel strengths for the comparative and inventive drilling fluids were measured.","The drilling fluids were then hot rolled for 16 hours at 40° F. and 150° F. and the after hot roll rheology, plastic viscosity, yield point, electrical stability, ten second gel strengths, and ten minute gel strength were measured.","The rheology properties of the comparative and inventive drilling fluids are shown in Table 14.TABLE 14 Rheology Properties With the Addition of API Clay Comparative Inventive Drilling Fluid Drilling Fluid AHR AHR AHR AHR Rheology BHR 40° F. 150° F. BHR 40° F. 150° F. 600 rpm 73 232 67 63 216 69 300 rpm 51 138 41 41 128 42 200 rpm 42 103 34 32 97 33 100 rpm 32 66 25 23 62 24 6 rpm 20 23 13 13 21 12 3 rpm 19 20 12 1 18 12 PV 22 94 26 22 88 27 YP 29 44 15 19 40 15 10″ Gel 18 23 15 12 19 12 10′ Gel 22 29 17 15 23 16 Table 15 shows the results of the electrical stability test for the comparative drilling fluid using C2 and the inventive drilling fluid using Ex 2.TABLE 15 Electrical Stability With API Clay Comparative Inventive Drilling Fluid Drilling Fluid BHR AHR 150° F. BHR AHR 150° F. ES (Volts at 150° F.) 500 783 508 665 Table 16 shows the results for the high temperature/high pressure water loss test for the inventive drilling fluid using C2 and the inventive drilling fluid using Ex 2.TABLE 16 High Temperature/High Pressure and Water Loss With API Clay Comparative Inventive Drilling Fluid Drilling Fluid AHR 150° F. AHR 150° F. HT/HP at 250° F. 11.4 11.6 Water Loss 0 0 Synthesis of Emulsifier C3 A condenser and a Barrett trap were attached to a reaction vessel.","To the reaction vessel were added 446.5 g of soybean oil and 453.5 g of Tall Oil Fatty Acid.","The mixture was heated to 90° C. under nitrogen.","To the soybean oil and Tall Oil Fatty Acid mixture was slowly added 163.7 g of diethylenetriamine to make a reaction mixture.","The temperature of the reaction mixture was increased to approximately 120° C. over approximately 30 minutes.","The reaction mixture was then heated to 130° C. for 2 hours and 160° C. for an additional 4 hours.","The reaction mixture was the cooled to 85° C., and decanted.","The isolated amidoamine had a final acid value of 11.8 mg KOH/gram of sample and a total amine value of 94.3 mg KOH/gram of sample.","To 1,053.6 g of the isolated amidoamine, which was heated to 70° C., was slowly added 188.3 g of maleic anhydride.","The reaction mixture increased in temperature to approximately 80° C. over approximately a 30 minute period.","The triamide reaction product was a waxy, brown solid obtained in a 93% yield with a final acid value of 64 mg KOH/gram of sample and a total amine value of 21.1 mg KOH/gram of sample.","The triamide reaction product was mixed with a modified tall oil product to produce a mixture that had an acid value of 197.3 mg KOH/gram of sample and a total amine value of 6.2 mg KOH/gram of sample.","The mixture of the triamide and modified tall oil product (240 g) was heated to 50° C. and neutralized by slowly adding to a solution of 240 grams of tap water and 67.5 grams of 50% sodium hydroxide solution.","The final acid number of the neutralized product was adjusted to 0.6 mg KOH/gram of solution and a solids content of 48.8 wt %.","This solution was then spray dried on a Niro laboratory spray dryer.","Synthesis of Emulsifier Ex.","3 A condenser and a Barrett trap were attached to a reaction vessel.","To the reaction vessel were added 429.4 g of soybean oil and 419.3 g of Tall Oil Fatty Acid.","The mixture was heated to 90° C. under nitrogen.","To the soybean oil and Tall Oil Fatty Acid blend was slowly added 151.3 g of diethylenetriamine to make a reaction mixture.","The temperature of the reaction mixture increased to approximately 120° C. over approximately 30 minutes.","The reaction mixture was then heated to 130° C. for 2 hours and to 160° C. for an additional 4 hours.","The reaction mixture was cooled to 85° C. and then decanted.","The isolated amidoamine had a final acid value of 11.6 mg KOH/ gram of sample and a total amine value of 93.1 mg KOH/gram of sample.","To 298.1 g of the isolated reaction mixture heated to 130° C. was added 33.3 g of succinic anhydride.","The reaction mixture increased in temperature to approximately 140° C. over approximately a 30 minute period.","The triamide reaction product was a waxy, brown solid obtained in a 93% yield with a final acid value of 38.5 mg KOH/gram of sample and a total amine value of 29.5 mg KOH/gram of sample.","The triamide was then blended with modified tall oil product in a ratio of 65 wt % modified tall oil product to 35 wt % of carboxyl terminated amidoamine made from tall oil fatty acids.","The resulting mixture had an acid value of 184.8 mg KOH/gram of sample and a total amine value of 8.3 mg KOH/gram of sample.","The mixture of the triamide and modified tall oil product (200 g) was then heated to 90° C. and neutralized by slowly adding a solution of 200 grams of tap water and 52.7 grams of 50% sodium hydroxide solution.","The final acid number of the neutralized product was adjusted to 0.2 mg KOH/gram of solution and a solids content of 48.5 wt %.","This solution was then spray dried on a Niro laboratory spray dryer.","Drilling Fluids for Emulsifiers C3 and Ex.","3 The drilling fluids were prepared by combining the ingredients in a Hamilton Beach mixer and then shearing the composition for 5 minutes at 6,000 rpm in a Silverson shear mixer.","The compositions for the comparative drilling fluid and the inventive drilling fluid are shown in Table 17.TABLE 17 Drilling Fluids Comparative Inventive Mix time Drilling Fluid Drilling Fluid after addition #2 Diesel 180.5 g 180.5 g VG-Plus 6 g 6 g 10 minutes Lime 2 g 2 g 5 minutes Emulsifier C3 5 g 0 g Emulsifier Ex.","3 0 g 5 g 25 wt % CaCl2 (aq) 71.5 g 71.5 g 10 minutes Barite 281 g 281 g 5 minutes Both the comparative drilling fluid and the inventive drilling fluid were of the same compositions except for the triamide used.","The comparative drilling fluid used comparative emulsifier (C3).","The comparative emulsifier was a mixture of tall oil and a triamide of Formula (I) except R4 was a C2-alkylene diyl group (e.g., ethylene group).","The inventive drilling fluid used emulsifier (Ex.","3), which was a spray dried mixture of tall oil and triamide of Formula (I) where R4 was a C2-alkenylene diyl group (e.g., ethylene diyl group).","The before hot roll rheology, plastic viscosity, yield point, electrical stability, and gel strengths for the comparative and inventive drilling fluids were measured.","Then, the drilling fluids were hot rolled for 16 hours at 40° F. and 150° F. and the after hot roll rheology, plastic viscosity, yield point, electrical stability, ten second gel strengths, and ten minute gel strength were measured.","Table 18 shows the results for the rheology tests.","TABLE 18 Rheology Properties Comparative Inventive Drilling Fluid Drilling Fluid AHR AHR AHR AHR Rheology BHR 40° F. 150° F. BHR 40° F. 150° F. 600 rpm 52 197 66 53 195 62 300 rpm 32 119 39 32 115 35 200 rpm 24 90 32 24 87 30 100 rpm 18 58 24 18 55 21 6 rpm 10 19 13 10 18 12 3 rpm 9 17 13 9 15 1 PV 20 78 27 21 80 27 YP 12 41 12 11 35 8 10″ Gel 10 18 14 11 17 13 10′ Gel 11 27 16 12 22 16 The electric stability Table 19 shows the results of the electrical stability test for the comparative drilling fluid using C3 and the inventive drilling fluid using Ex 3.TABLE 19 Electrical Stability Comparative Inventive Drilling Fluid Drilling Fluid BHR AHR 150° F. BHR AHR 150° F. ES (Volts at 150° F.) 833 1151 824 1145 Table 20 shows the results for the high temperature/high pressure water loss test for the comparative drilling fluid using C3 and the inventive drilling fluid using Ex 3.TABLE 20 High Temperature/High Pressure and Water Loss Comparative Inventive Drilling Fluid Drilling Fluid AHR 150° F. AHR 150° F. HT/HP at 250° F. 10.2 8.2 Water Loss 0 0 Comparative and inventive drilling fluids were made again with the addition of API grade bentonite clay.","The compositions are shown in Table 21.TABLE 21 Drilling Fluids With API Clay Comparative Inventive Mix time Drilling Fluid Drilling Fluid after addition #2 Diesel 180.5 g 180.5 g VG-Plus 6 g 6 g 10 minutes Lime 2 g 2 g 5 minutes Emulsifier C3 5 g 0 g Emulsifier Ex.","3 0 g 5 g 25 wt % CaCl2 (aq) 71.5 g 71.5 g 10 minutes Barite 281 g 281 g 5 minutes API Clay 20 g 20 g 5 minutes The before hot roll rheology, plastic viscosity, yield point, electrical stability, and gel strengths for the comparative and inventive drilling fluids were measured.","The drilling fluids were then hot rolled for 16 hours at 40° F. and 150° F., and the after hot roll rheology, plastic viscosity, yield point, electrical stability, ten second gel strengths, and ten minute gel strength were measured.","Table 22 shows the results for the rheology tests.","TABLE 22 Rheology Properties with the addition of API Clay Comparative Inventive Drilling Fluid Drilling Fluid AHR AHR AHR AHR Rheology BHR 40° F. 150° F. BHR 40° F. 150° F. 600 rpm 61 221 66 63 242 73 300 rpm 38 130 39 39 143 43 200 rpm 31 96 32 31 107 35 100 rpm 23 60 24 23 68 25 6 rpm 13 20 13 12 21 13 3 rpm 12 18 12 11 18 12 PV 23 91 27 24 99 30 YP 15 39 12 15 44 13 10″ Gel 13 20 14 12 19 14 10′ Gel 17 27 18 15 26 18 Table 23 shows the results of the electrical stability test for the comparative drilling fluid using C3 and the inventive drilling fluid using Ex 3.TABLE 23 Electrical stability Comparative Inventive Drilling Fluid Drilling Fluid BHR AHR 150° F. BHR AHR 150° F. ES (Volts at 150° F.) 464 683 549 870 Table 24 shows the results for the high temperature/high pressure water loss test for the comparative drilling fluid using C3 and the inventive drilling fluid using Ex 3.TABLE 24 High Temperature/High Pressure and Water Loss Comparative Inventive Drilling Fluid Drilling Fluid AHR 150° F. AHR 150° F. HT/HP at 250° F. 10.8 10.8 Water Loss 0 0 Synthesis of Emulsifier C4 A condenser and a Barrett trap were attached to a reaction vessel.","To the reaction vessel were added 502.2 g of Palm Olein and 512.3 g of Tall Oil Fatty Acid.","The mixture was heated to 90° C. under nitrogen.","To the soybean oil and Tall Oil Fatty Acid mixture was slowly added 185.5 g of diethylenetriamine.","The temperature of the reaction mixture increased to approximately 120° C. over approximately 30 minutes.","The reaction mixture was then heated to 130° C. for 2 hours and to 160° C. for an additional 4 hours.","The reaction mixture was cooled to 85° C. and decanted.","The isolated amidoamine had a final acid value of 11.7 mg KOH/gram of sample and a total amine value of 117.5 mg KOH/gram of sample.","To 350 g of the isolated reaction mixture, which was heated to 70° C., was added 41.7 g of maleic anhydride.","The reaction mixture increased in temperature to approximately 90° C. over 30 minutes.","The triamide reaction product was a waxy, brown solid obtained in a 93% yield with a final acid value of 50 mg KOH/gram of sample and a total amine value of 22.7 mg KOH/gram of sample.","The triamide was then mixed with a modified tall oil product in a ratio of 65 wt % modified tall oil product to 35 wt % of the carboxyl terminated amidoamine.","The mixture of the triamide and the modified tall oil product had an acid value of 197.2 mg KOH/gram of sample and a total amine value of 6.7 mg KOH/gram of sample.","The mixture of the triamide and the modified tall oil product (200 g) of the mixture was heated to 50° C. and neutralized by slowly adding a solution of 200 grams of tap water and 56.3 grams of 50% sodium hydroxide solution.","The final acid number of the neutralized product was adjusted to 0.3 mg KOH/gram of solution and a solids content of 48.9 wt %.","This solution was then spray dried on a Niro laboratory spray dryer.","Synthesis of Emulsifier Ex.","4 A condenser and a Barrett trap were attached to a reaction vessel.","To the reaction vessel were added 502.2 g of Palm Olein and 512.3 g of Tall Oil Fatty Acid to form a mixture.","The mixture was heated to 90° C. under nitrogen.","To the soybean oil and Tall Oil Fatty Acid mixture was slowly added 185.5 g of diethylenetriamine to form a reaction mixture.","The temperature of the reaction mixture increased to approximately 120° C. for 30 minutes.","The reaction mixture was then heated to 130° C. for 2 hours and then to 160° C. for approximately 4 hours.","The reaction mixture was cooled to 85° C. and decanted.","The isolated amidoamine had a final acid value of 11.7 mg KOH/gram of sample and a total amine value of 117.5 mg KOH/gram of sample.","To 350 g of the isolated reaction mixture, which was heated to 125° C., was slowly added 42.6 g of succinic anhydride.","The reaction mixture increased in temperature to approximately 137° C. over approximately a 30 minute period.","The triamide reaction product was a waxy, brown solid obtained in a 93% yield with a final acid value of 52.4 mg KOH/gram of sample and a total amine value of 30 mg KOH/gram of sample.","The triamide was then mixed with a modified tall oil product in a ratio of 65 wt % modified tall oil product to 35 wt % of carboxyl terminated amidoamine.","The mixture of the triamide and the modified tall oil product had an acid value of 180 mg KOH/gram of sample and a total amine value of 10 mg KOH/gram of sample.","The mixture of the triamide and the modified tall oil product (200 g) of the mixture was heated to 50° C. and neutralized by slowly adding a solution of 200 grams of tap water and 51.4 grams of 50% sodium hydroxide solution.","The final acid number of the neutralized product was adjusted to 0.2 mg KOH/gram of solution and a solids content of 49.1%.","This solution was then spray dried on a Niro laboratory spray dryer.","The drilling fluids were prepared by combining the ingredients in a Hamilton Beach mixer and then shearing the composition for 5 minutes at 6,000 rpm in a Silverson shear mixer.","The compositions for the comparative drilling fluid and the inventive drilling fluid are shown in Table 25.TABLE 25 Drilling Fluids Comparative Inventive Mix time Drilling Fluid Drilling Fluid after addition #2 Diesel 180.5 g 180.5 g VG-Plus 6 g 6 g 10 minutes Lime 2 g 2 g 5 minutes Emulsifier C4 5 g 0 g Emulsifier Ex.","4 0 g 5 g 25 wt % CaCl2 (aq) 71.5 g 71.5 g 10 minutes Barite 281 g 281 g 5 minutes Both the comparative drilling fluid and the inventive drilling fluid were of the same compositions except for the triamide used.","The comparative drilling fluid used comparative emulsifier (C4).","The comparative emulsifier was a mixture of tall oil and a triamide of Formula (I) except R4 was a C2-alkylene diyl group (e.g., ethylene group).","The inventive drilling fluid used emulsifier (Ex.","4), which was a spray dried mixture of tall oil and triamide of Formula (I) where R4 was a C2-alkenylene diyl group (e.g., ethylene diyl group).","The before hot roll rheology, plastic viscosity, yield point, electrical stability, and gel strengths for the comparative and inventive drilling fluids were measured.","Then, the drilling fluids were hot rolled for 16 hours at 40° F. and 150° F. and the after hot roll rheology, plastic viscosity, yield point, electrical stability, ten second gel strengths, and ten minute gel strength were measured.","Table 26 shows the results for the rheology tests.","TABLE 26 Rheology Properties Comparative Inventive Drilling Fluid Drilling Fluid AHR AHR AHR AHR Rheology BHR 40° F. 150° F. BHR 40° F. 150° F. 600 rpm 54 220 70 52 188 64 300 rpm 34 136 45 31 113 39 200 rpm 25 105 37 24 86 31 100 rpm 18 70 28 18 56 22 6 rpm 10 25 17 9 19 13 3 rpm 9 23 16 9 17 12 PV 20 84 25 21 75 25 YP 14 52 20 10 38 14 10″ Gel 7 24 16 9 19 14 10′ Gel 10 34 19 10 24 16 Table 27 shows the results of the electrical stability test for the comparative drilling fluid using C4 and the inventive drilling fluid using Ex 4.TABLE 27 Electrical stability Comparative Inventive Drilling Fluid Drilling Fluid BHR AHR 150° F. BHR AHR 150° F. ES (Volts at 150° F.) 770 1203 764 1170 Table 28 shows the results for the high temperature/high pressure water loss test for the comparative drilling fluid using C4 and the inventive drilling fluid using Ex 4.TABLE 28 High Temperature/High Pressure and Water Loss Comparative Inventive Drilling Fluid Drilling Fluid AHR 150° F. AHR 150° F. HT/HP at 250° F. 12.2 11.0 Water Loss 0.4 0.4 Comparative and inventive drilling fluids were made again with the addition of API grade bentonite clay.","The compositions are shown in Table 29.TABLE 29 Drilling Fluids With API Clay Comparative Inventive Mix time Drilling Fluid Drilling Fluid after addition #2 Diesel 180.5 g 180.5 g VG-Plus 6 g 6 g 10 minutes Lime 2 g 2 g 5 minutes Emulsifier C4 5 g 0 g Emulsifier Ex.","4 0 g 5 g 25 wt % CaCl2 (aq) 71.5 g 71.5 g 10 minutes Barite 281 g 281 g 5 minutes API Clay 20 g 20 g 5 minutes The before hot roll rheology, plastic viscosity, yield point, electrical stability, and gel strengths for the comparative and inventive drilling fluids were measured.","The drilling fluids were then hot rolled for 16 hours at 40° F. and 150° F., and the after hot roll rheology, plastic viscosity, yield point, electrical stability, ten second gel strengths, and ten minute gel strength were measured.","Table 30 shows the results for the rheology tests.","TABLE 30 Rheology Properties With API Clay Comparative Inventive Drilling Fluid Drilling Fluid AHR AHR AHR AHR Rheology BHR 40° F. 150° F. BHR 40° F. 150° F. 600 rpm 54 249 69 57 217 75 300 rpm 32 147 42 33 132 47 200 rpm 26 110 34 25 102 38 100 rpm 19 70 25 18 69 28 6 rpm 10 25 14 9 26 16 3 rpm 10 21 12 9 23 15 PV 22 102 27 24 85 28 YP 10 45 15 9 47 19 10″ Gel 10 21 14 10 22 17 10′ Gel 13 27 18 11 29 21 Table 31 shows the results of the electrical stability test for the comparative drilling fluid using C4 and the inventive drilling fluid using Ex 4.TABLE 31 Electrical Stability With API Clay Comparative Inventive Drilling Fluid Drilling Fluid BHR AHR 150° F. BHR AHR 150° F. ES (Volts at 150° F.) 391 600 360 551 Table 32 shows the results for the high temperature/high pressure water loss test for the comparative drilling fluid using C4 and the inventive drilling fluid using Ex 4.TABLE 32 High Temperature/High Pressure and Water Loss With API Clay Comparative Inventive Drilling Fluid Drilling Fluid AHR 150° F. AHR 150° F. HT/HP at 250° F. 14.8 14.6 Water Loss 0.2 0.2 Embodiments of the present disclosure further relate to any one or more of the following paragraphs: 1.A method for making an emulsifier, comprising: mixing a tall oil and a triamide, wherein the triamide has the chemical formula: wherein: x, y, and z are integers independently selected from 1 to 10, R1 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl, R2 is H or independently selected for each [(CH2)xNR2(CH2)y] unit, wherein R4 is a C1-C3 alkylene or a C1-C3 alkylene alcohol, and wherein at least one R2 is and R3 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl.","2.The method according to paragraph 1, wherein the mixture has a triamide to tall oil weight ratio of about 1:4 to about 2:3.3.The method according to paragraph 1 or 2, wherein R4 is an ethanediyl group (—CH2CH2—).","4.The method according to any one of paragraphs 1 to 3, further comprising spray drying the mixture to produce a spray dried emulsifier having an average particle size of about 1 μm to about 75 μm.","5.The method according to any one of paragraphs 1 to 4, wherein the emulsifier is at least partially neutralized before spray drying.","6.The method according to any one of paragraphs 1 to 5, wherein the mixture is diluted with an aqueous diluent to provide a solids content of about 35 wt % to about 50 wt %, based on the weight of the emulsifier prior to spray drying.","7.The method according to any one of paragraphs 1 to 6, wherein the spray dried emulsifier has an average particle size of about 30 μm to about 75 μm.","8.The method according to any one of paragraphs 1 to 7, wherein the spray dried emulsifier has a bulk density of about 0.24 g/mL to about 0.56 g/mL.","9.The method according to any one of paragraphs 1 to 8, wherein the tall oil comprises crude tall oil, distillate tall oil, tall oil bottoms, or any mixture thereof.","10.The method according to any one of paragraphs 1 to 9, wherein the tall oil comprises is a reaction product of at least tall oil and an α, β unsaturated carboxylic acid or an α,β unsaturated acid anhydride.","11.The method according to any one of paragraphs 1 to 10, wherein the tall oil is a Diels-Alder product, an ene product, or any mixture thereof.","12.The method according to any one of paragraphs 1 to 11, wherein the Diels-Alder product, the ene product, or the mixture thereof is oxidized to provide an ether bond between at least two or more hydrocarbon backbones.","13.The method according to any one of paragraphs 1 to 12, wherein the tall oil is dimerized by a carbon-carbon bond between at least two or more hydrocarbon backbones.","14.The method according to any one of paragraphs 1 to 13, wherein the tall oil is oxidized to provide an ether bond between at least two or more hydrocarbon backbones.","15.The method according to any one of paragraphs 1 to 14, wherein the tall oil comprises a mixture of a first tall oil distillate fraction and a second tall oil distillate fraction comprising about 45 wt % to about 90 wt % of fatty acids and about 10 wt % to about 55 wt % of rosin acids, based on the combined weight of the first tall oil distillate fraction and the second tall oil distillate fraction.","16.A method for making an emulsifier, comprising: mixing a triamide and a tall oil, wherein the triamide is prepared by reacting a diamidoamine with a saturated dicarboxylic acid, a saturated acid anhydride, or a mixture thereof; and spray drying the mixture to provide a spray dried emulsifier.","17.The method according to paragraph of 16, wherein the mixture has a triamide to tall oil weight ratio of about 1:4 to about 2:3.18.The method according to paragraph 16 or 17, wherein the saturated dicarboxylic acid is succinic acid or the saturated anhydride is succinic anhydride.","19.The method according to any one of paragraphs of 16 to 18, wherein the saturated dicarboxylic acid is glutaric acid or the saturated anhydride is glutaric anhydride.","20.The method according to any one of paragraphs of 16 to 19, wherein the diamidoamine is a reaction product from one or more fatty acids and one or more polyamines.","21.The method according to any one of paragraphs of 16 to 20, wherein the one or more polyamine has the formula H2[(CH2)xNH]yH, wherein x and y are integers independently selected from 1 to 10.22.The method according to any one of paragraphs of 16 to 21, wherein emulsifier is at least partially neutralized before spray drying.","23.The method according to any one of paragraphs of 16 to 22, wherein the emulsifier has, or is diluted with an aqueous diluent to provide, a solids content of about 35 wt % to about 50 wt %, based on the weight of the emulsifier prior to spray drying.","24.The method according to any one of paragraphs of 16 to 23, wherein the tall oil comprises crude tall oil, distillate tall oil, tall oil bottoms, or any mixture thereof.","25.The method according to any one of paragraphs of 16 to 24, wherein the tall oil comprises a mixture of a first tall oil distillate fraction and a second tall oil distillate fraction comprising about 45 wt % to about 90 wt % of fatty acids and about 10 wt % to about 55 wt % of rosin acids, based on the combined weight of the first tall oil distillate fraction and the second tall oil distillate fraction.","26.The method according to any one of paragraphs of 16 to 25, wherein the tall oil comprises is a reaction product of at least tall oil and an α,β unsaturated carboxylic acid or an α,β unsaturated acid anhydride.","27.The method according to any one of paragraphs of 16 to 26, wherein the tall oil is a Diels-Alder product, an Alder-ene product, or any mixture thereof.","28.The method according to any one of paragraphs of 16 to 27, wherein the Diels-Alder product, the ene product, or the mixture thereof is oxidized to provide an ether bond between at least two or more hydrocarbon backbones.","29.The method according to any one of paragraphs of 16 to 28, wherein the tall oil is dimerized by a carbon-carbon bond between at least two or more hydrocarbon backbones.","30.The method according to any one of paragraphs of 16 to 29, wherein the tall oil is oxidized to provide an ether bond between at least two or more hydrocarbon backbones.","31.A method for making a drilling fluid, comprising: mixing an oil phase, an aqueous phase, and a spray dried emulsifier to produce a drilling fluid, wherein the spray dried emulsifier comprises a mixture of a tall oil and a triamide, wherein the triamide has the chemical formula: wherein: x, y, and z are integers independently selected from 1 to 10, R1 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl, R2 is H or independently selected for each [(CH2)xNR2(CH2)y] unit, wherein R4 is a C1-C3 alkylene or a C1-C3 alkylene alcohol, and wherein at least one R2 is and R3 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl.","32.The method according to paragraph 31, wherein the spray dried emulsifier is present in the drilling fluid in an amount of about 1 wt % to about 5 wt %, based on the weight of the oil phase, the aqueous phase, and the spray dried emulsifier.","33.The method according to paragraph 31 or 32, wherein R4 is an ethanediyl group (—CH2CH2—).","Certain embodiments and features have been described using a set of numerical upper limits and a set of numerical lower limits.","It should be appreciated that ranges including the combination of any two values, e.g., the combination of any lower value with any upper value, the combination of any two lower values, and/or the combination of any two upper values are contemplated unless otherwise indicated.","Certain lower limits, upper limits and ranges appear in one or more claims below.","All numerical values are “about” or “approximately” the indicated value, and take into account experimental error and variations that would be expected by a person having ordinary skill in the art.","Various terms have been defined above.","To the extent a term used in a claim is not defined above, it should be given the broadest definition persons in the pertinent art have given that term as reflected in at least one printed publication or issued patent.","Furthermore, all patents, test procedures, and other documents cited in this application are fully incorporated by reference to the extent such disclosure is not inconsistent with this application and for all jurisdictions in which such incorporation is permitted.","While the foregoing is directed to embodiments of the present invention, other and further embodiments of the invention may be devised without departing from the basic scope thereof, and the scope thereof is determined by the claims that follow."]],"string":"[\n [\n \"METHODS FOR PRODUCING EMULSIFIERS FOR OIL-BASED DRILLING FLUIDS\",\n \"Methods for making emulsifiers, emulsified drilling fluids, and methods for using the same are provided.\",\n \"In one or more embodiments, the method for making an emulsifier can include mixing a tall oil and a triamide.\",\n \"The triamide can have the chemical formula: where: x, y, and z are integers independently selected from 1 to 10, R1 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl, R2 is H or independently selected for each [(CH2)xNR2(CH2)y] unit, where R4 is a C1-C3 alkylene or a C1-C3 alkylene alcohol, and where at least one R2 is and R3 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl.\"\n ],\n [\n \"1.An emulsifier, comprising: a tall oil component; and a triamide component.\",\n \"2.The emulsifier of claim 1, wherein the triamide component comprises a triamide having the chemical formula: wherein: x, y, and z are integers independently selected from 1 to 10, R1 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl, R2 is H or independently selected for each [(CH2)xNR2(CH2)y] unit, wherein R4 is a C1-C3 alkylene or a C1-C3 alkylene alcohol, and wherein at least one R2 is and R3 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl.\",\n \"3.The emulsifier of claim 1, wherein the triamide component comprises an alkali metal salt of a triamide, an alkaline earth metal salt of a triamide, or a mixture thereof.\",\n \"4.The emulsifier of claim 1, wherein the triamide component comprises an alkali metal salt of a triamide, and wherein the triamide the chemical formula: wherein: x, y, and z are integers independently selected from 1 to 10, R1 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl, R2 is H or independently selected for each [(CH2)xNR2(CH2)y] unit, wherein R4 is a C1-C3 alkylene or a C1-C3 alkylene alcohol, and wherein at least one R2 is and R3 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl.\",\n \"5.The emulsifier of claim 4, wherein R4 is an ethanediyl group (—CH2CH2—).\",\n \"6.The emulsifier of claim 1, wherein the triamide component comprises an alkaline earth metal salt of a triamide, and wherein the triamide the chemical formula: wherein: x, y, and z are integers independently selected from 1 to 10, R2 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl, R2 is H or independently selected for each [(CH2)xNR2(CH2)y] unit, wherein R4 is a C1-C3 alkylene or a C1-C3 alkylene alcohol, and wherein at least one R2 is and R3 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl.\",\n \"7.The emulsifier of claim 6, wherein R4 is an ethanediyl group (—CH2CH2—).\",\n \"8.The emulsifier of claim 1, wherein the tall oil component comprises a tall oil.\",\n \"9.The emulsifier of claim 1, wherein the tall oil component comprises an alkali metal salt of a tall oil.\",\n \"10.The emulsifier of claim 1, wherein the tall oil component comprises an alkaline earth metal salt of a tall oil.\",\n \"11.The emulsifier of claim 1, wherein the emulsifier is a spray dried emulsifier and has an average particle size of about 1 μm to about 75 μm.\",\n \"12.The emulsifier of claim 1, wherein the tall oil comprises a crude tall oil, a distillate tall oil, a tall oil bottoms, or a mixture thereof.\",\n \"13.The method of claim 1, wherein the tall oil component comprises a modified tall oil produced by reacting a tall oil and an α,β unsaturated carboxylic acid or an α,β unsaturated acid anhydride.\",\n \"14.The method of claim 1, wherein the tall oil component comprises a mixture of a first tall oil distillate fraction and a second tall oil distillate fraction comprising about 45 wt % to about 90 wt % of fatty acids and about 10 wt % to about 55 wt % of rosin acids, based on the combined weight of the first tall oil distillate fraction and the second tall oil distillate fraction.\",\n \"15.A process for making an emulsifier, comprising: mixing a tall oil component and a triamide component to produce a mixture; and spray drying the mixture to produce a spray dried emulsifier.\",\n \"16.The process of claim 15, wherein the triamide component is produced by reacting a diamidoamine with a saturated dicarboxylic acid, a saturated acid anhydride, or a mixture thereof, and wherein the tall oil component is produced by reacting a tall oil and an α,β unsaturated carboxylic acid or an α,β unsaturated acid anhydride.\",\n \"17.The process of claim 15, further comprising neutralizing the mixture to produce a neutralized mixture, wherein the neutralized mixture is spray dried to produce the spray dried emulsifier.\",\n \"18.A drilling fluid, comprising: an oil phase; an aqueous phase, and a spray dried emulsifier comprising a mixture of a tall oil component and a triamide component.\",\n \"19.The drilling fluid of claim 19, wherein: the oil phase comprises paraffins, olefins, aromatics, naphthalenes, or a mixture thereof, the aqueous phase comprises a brine solution containing sodium chloride, potassium chloride, magnesium chloride, calcium chloride, or a mixture thereof, the triamide component comprises an alkali metal salt of a triamide, an alkaline earth metal salt of a triamide, or a mixture thereof, and the tall oil component comprises an alkali metal salt of a tall oil, an alkaline earth metal salt of a tall oil, or a mixture thereof.\",\n \"20.The drilling fluid of claim 19, wherein the drilling fluid comprises about 0.2 wt % to about 5 wt % of the spray dried emulsifier and about 5 wt % to about 40 wt % of the aqueous phase, based on a combined weight of the oil phase, the aqueous phase, and the spray dried emulsifier.\"\n ],\n [\n \" BACKGROUND \"\n ],\n [\n \" SUMMARY Methods for making emulsifiers, emulsified drilling fluids, and methods for using the same are provided.\",\n \"In one or more embodiments, the method for making an emulsifier can include mixing a tall oil and a triamide.\",\n \"The triamide can have the general chemical formula, Formula (I): where: x, y, and z are integers independently selected from 1 to 10, R 1 is a C 8 -C 20 alkyl, a C 8 -C 20 alkenyl, a C 8 -C 20 dialkenyl, or a C 8 -C 20 alkynyl, R 2 is H or independently selected for each [CH 2 ) x NR 2 (CH 2 ) y ] unit, where R 4 is a C 1 -C 3 alkylene or a C 1 -C 3 alkylene alcohol, and where at least one R 2 is and R 3 is a C 8 -C 20 alkyl, a C 8 -C 20 alkenyl, a C 8 -C 20 dialkenyl, or a C 8 -C 20 alkynyl.\",\n \"In some embodiments, the method for making an emulsifier can include mixing a triamide and a tall oil.\",\n \"The triamide can be prepared by reacting a diamidoamine with a saturated dicarboxylic acid, a saturated acid anhydride, or a mixture thereof.\",\n \"The method can also include spray drying the emulsifier to provide a spray dried emulsifier.\",\n \"The method for making a drilling fluid can include mixing an oil phase, an aqueous phase, and a spray dried emulsifier to produce a drilling fluid.\",\n \"The spray dried emulsifier can include a mixture of a tall oil and a triamide, where the triamide can have Formula (I).\",\n \"detailed-description description=\\\"Detailed Description\\\" end=\\\"lead\\\"?\"\n ],\n [\n \"CROSS-REFERENCE TO RELATED APPLICATION This application is a continuation of co-pending U.S. patent application Ser.\",\n \"No.\",\n \"14/461,460, filed on Aug. 18, 2014, which claims priority to U.S.\",\n \"Provisional Patent Application No.\",\n \"61/867,328, filed Aug. 19, 2013, which are both incorporated by reference herein.\",\n \"BACKGROUND Field Embodiments described generally relate to methods for making emulsifiers that can include one or more tall oils and one or more triamides, emulsified drilling fluids, and methods for using same.\",\n \"Description of the Related Art The oil and gas industry has used drilling fluids or “drilling muds” for a number of years to tap subterranean deposits of natural resources.\",\n \"As the total reserves of oil diminish, it has become necessary to drill in areas that were previously inaccessible due to technological or economic difficulties.\",\n \"This has led to the widespread use of oil-based drilling fluids or invert emulsion drilling fluids, which offer greater thermal and chemical stability than water-based fluids, allowing for drilling at extended depths and in other demanding services, such as those involving exposure to high electrolyte concentrations and soluble gases.\",\n \"For example, invert emulsion drilling fluids have been used successfully in drilling hot (e.g., greater than 150° C.) formations as well as those containing hydrogen sulfide.\",\n \"Also, to maximize recovery from each platform in offshore drilling, invert emulsion drilling fluids are favored due to their effectiveness for drilling deviated wells (e.g., angled wells).\",\n \"In particular, the high lubricity of invert emulsion drilling fluids is necessary because of the increased torque exerted on the drill string in deviated drilling.\",\n \"Invert emulsion drilling fluids are typically formed by blending a hydrocarbon oil with water or brine under high shear conditions and in the presence of a suitable emulsifier.\",\n \"The emulsifier is required not only to form a stable dispersion of water droplets in the oil phase, but also to maintain any solids such as weighting material additives (e.g., barites) or drill cuttings in an oil-wet state.\",\n \"With space at some well sites limited, such as on offshore platforms, and with increasing costs of transport of materials to a well site, there is industry wide interest particularly in drilling fluid compositions that can be formulated and maintained (e.g., stored) with minimal or fewer quantities of solvent and other additives, compared to prior art compositions.\",\n \"There is a need, therefore, for improved emulsifiers for use in invert emulsions that can be used, for example, in oil well drilling.\",\n \"SUMMARY Methods for making emulsifiers, emulsified drilling fluids, and methods for using the same are provided.\",\n \"In one or more embodiments, the method for making an emulsifier can include mixing a tall oil and a triamide.\",\n \"The triamide can have the general chemical formula, Formula (I): where: x, y, and z are integers independently selected from 1 to 10, R1 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl, R2 is H or independently selected for each [CH2)xNR2(CH2)y] unit, where R4 is a C1-C3 alkylene or a C1-C3 alkylene alcohol, and where at least one R2 is and R3 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl.\",\n \"In some embodiments, the method for making an emulsifier can include mixing a triamide and a tall oil.\",\n \"The triamide can be prepared by reacting a diamidoamine with a saturated dicarboxylic acid, a saturated acid anhydride, or a mixture thereof.\",\n \"The method can also include spray drying the emulsifier to provide a spray dried emulsifier.\",\n \"The method for making a drilling fluid can include mixing an oil phase, an aqueous phase, and a spray dried emulsifier to produce a drilling fluid.\",\n \"The spray dried emulsifier can include a mixture of a tall oil and a triamide, where the triamide can have Formula (I).\",\n \"DETAILED DESCRIPTION Methods for making emulsifiers, emulsified drilling fluids, and methods for using the same are provided.\",\n \"In one or more embodiments, the emulsifier can be made by mixing, blending, or otherwise combining one or more tall oils and one or more triamides.\",\n \"The one or more triamides can be represented by the general chemical formula, Formula (I): where: x, y, and z are integers independently selected from 1 to 10, R2 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl, R2 is H or independently selected for each [CH2)xNR2(CH2)y] unit, where R4 is a C1-C3 alkylene or a C1-C3 alkylene alcohol, and where at least one R2 is and R3 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl.\",\n \"The C1-C3 alkylene for R4 can include, but is not limited to, a methylene or methanediyl group (—CH2—), an ethylene or ethanediyl group (—CH2CH2—), and a propylene or propanediyl group (—CH2CH2CH2—), which provides a saturated alkane moiety in the triamide.\",\n \"The C1-C3 alkylene alcohol for R4 can include, but is not limited to, a methylene or methanediyl alcohol group (—C(OH)H—), an ethylene or ethanediyl alcohol group (—CH2C(OH)H—), and a propylene or propanediyl alcohol group (—CH2C(OH)HCH2— or —CH2CH2C(OH)H—), which provides a saturated alkane alcohol moiety in the triamide.\",\n \"In some embodiments, the emulsifier can be used for oil-based drilling fluids.\",\n \"It has been surprisingly and unexpectedly discovered that when R4 is a C1-C3 alkylene or a C1-C3 alkylene alcohol, e.g., a saturated carbon chain, the oil-based drilling fluids can exhibit one or more of the following properties: flatter low end rheology, lower high end rheology, higher electrical stability, lower plastic viscosity, lower gel strengths, and lower fluid loss to the subterranean formation, as compared to the same emulsifier, but having an unsaturated R4, e.g., an R4 having at least one carbon-carbon double bond.\",\n \"For example, the emulsifier having R4 as a C1-C3 alkylene or a C1-C3 alkylene alcohol can improve the low end rheology, the high end rheology, the electrical stability, the gel strengths, plastic viscosity, fluid break-through, and/or the fluid loss by about 0.2%, about 0.5%, about 1%, about 2%, about 3%, about 4%, about 5%, or about 10%, or more as compared to the same emulsifier but having an unsaturated R4, such as when R4 is alkenylene (e.g., —(CnH2n-2)—, where n is 1, 2, or 3).\",\n \"The one or more tall oils and the one or more triamides of the emulsifier can be combined with one another in any ratio.\",\n \"For example, the weight ratio of the triamide to the tall oil can be about 99:1, about 90:10, about 80:20, about 70:30, about 60:40, or about 50:50 to about 40:60, about 30:70, about 20:80, about 10:90, or about 1:99.In another example, the weight ratio of the triamide to tall oil can be about 0.5:1, about 1:1, about 2:3, about 3:7, or about 1:4.In another example, the weight ratio of the triamide to tall oil can be about 0.1:1 to about 3:1, about 0.2:1 to about 2.8:1, about 0.3:1 to about 2.5:1, about 0.4:1 to about 2.2:1, about 0.5:1 to about 2:1, about 0.3:1 to about 2:1, about 1:1 to about 3:1, about 0.4:1 to about 1:1, about 0.4:1 to about 0.7:1, or about 0.3:1 to about 1:1.In some embodiments, the emulsifier can have an acid value of about 100 mg of KOH, about 125 mg of KOH, or about 150 mg of KOH to about 250 mg of KOH, about 175 mg of KOH, about 200 mg of KOH, per gram of emulsifier.\",\n \"For example, the emulsifier can have an acid value of about 100 mg of KOH to about 150 mg of KOH, about 125 mg of KOH to about 175 mg of KOH, about 170 mg of KOH to about 200 mg of KOH, about 170 mg of KOH to about 225 mg of KOH, about 165 mg of KOH to about 230 mg of KOH, about 180 mg of KOH to about 220 mg of KOH, about 200 mg of KOH to about 250 mg of KOH, about 225 mg of KOH to about 250 mg of KOH, or about 250 mg of KOH to about 300 mg of KOH, per gram of emulsifier.\",\n \"In another example, the emulsifier can have an acid value of at least 100 mg of KOH, at least 110 mg of KOH, at least 120 mg of KOH, at least 130 mg KOH, at least 150 mg KOH, or at least 175 mg KOH.\",\n \"In another example, the emulsifier can have an acid value of less than 220 mg KOH, less than 170 mg KOH, or less than 150 mg KOH.\",\n \"As used herein, the term “acid value” refers to the mass of potassium hydroxide (KOH) in milligrams that is required to neutralize one gram of a reaction mixture or a composition.\",\n \"For example, the acid value of the emulsifier refers to the amount of KOH in milligrams required to neutralize one gram of the emulsifier.\",\n \"The acid value can be used as a measure of the amount of carboxylic acid groups in a reaction mixture or a composition.\",\n \"In a typical procedure, a known amount of the composition is dissolved in organic solvent and titrated with a solution of potassium hydroxide of known concentration.\",\n \"The acid value can be determined by using a potassium hydride solution that contains phenolphthalein as a color indicator or using potentiometric analysis.\",\n \"Standard methods used for determining acid value include ASTM D 465-05 and AOCS Te 1a-64.The rheology, electrical stability, gel strengths, plastic viscosity, yield point, high temperature/high pressure, fluid break-through, and fluid loss can be tested according to the API Recommended Practice Standard 13B-2, Third Edition, February 1998.The drilling fluid can have a rheology of about 3, about 5, or about 7 to about 15, about 17, or about 20, after hot roll at 3 rotations per minute (rpm) at 150° F. For example, the drilling fluid can have a rheology of about 4 to about 7, about 5 to about 10, about 6 to about 17, about 8 to about 15, or about 8 to about 28, after hot roll at 3 rpm at 150° F. The drilling fluid can have a rheology of about 3, about 5, or about 7 to about 15, about 17, about 23, about 27, or about 30, after hot roll at 6 rpm at 150° F. For example, the drilling fluid can have a rheology of about 4 to about 7, about 5 to about 10, about 6 to about 17, about 8 to about 15, or about 6 to about 28, after hot roll at 6 rpm at 150° F. The drilling fluid can have a rheology of about 45, about 50, or about 55 to about 70, about 75, about 85, after hot roll at 600 rpm at 150° F. For example, the drilling fluid can have a rheology of about 40 to about 70, about 50 to about 67, about 50 to about 70, or about 55 to about 85, after hot roll at 600 rpm at 150° F. The drilling fluid containing the emulsifier can have a ten second gel strength of about 3 lb/100 ft2, about 5 lb/100 ft2, or about 7 lb/100 ft2 to about 15 lb/100 ft2, about 17 lb/100 ft2, about 30 lb/100 ft2, after hot roll at 150° F. For example, the drilling fluid can have a ten second gel strength of about 4 lb/100 ft2 to about 7 lb/100 ft2, about 5 lb/100 ft2 to about 10 lb/100 ft2, about 6 lb/100 ft2 to about 17 lb/100 ft2, about 8 lb/100 ft2 to about 15 lb/100 ft2, or about 14 lb/100 ft2to about 28 lb/100 ft2, after hot roll at 150° F. The drilling fluid containing the emulsifier can have a ten minute gel strength of about 3 lb/100 ft2, about 5 lb/100 ft2, or about 7 lb/100 ft2 to about 15 lb/100 ft2, about 17 lb/100 ft2, about 30 lb/100 ft2, after hot roll at 150° F. For example, the drilling fluid can have a ten minute gel strength of about 4 lb/100 ft2 to about 7 lb/100 ft2, about 5 lb/100 ft2 to about 10 lb/100 ft2, about 6 lb/100 ft2 to about 17 lb/100 ft2, about 8 lb/100 ft2 to about 15 lb/100 ft2, or about 14 lb/100 ft2 to about 28 lb/100 ft2, after hot roll at 150° F. The drilling fluid containing the emulsifier can have a plastic viscosity of about 15 cP, about 17 cP, or about 19 cP to about 25 cP, about 27 cP, about 30 cP, after hot roll at 150° F. For example, the drilling fluid can have a plastic viscosity of about 15 cP to about 17 cP, about 5 cP to about 10 cP, about 6 cP to about 17 cP, about 8 cP to about 15 cP, or about 14 cP to about 28 cP, after hot roll at 150° F. The drilling fluid containing the emulsifier can have a yield point of about 3 lb/100 ft2, about 5 lb/100 ft2, or about 7 lb/100 ft2 to about 15 lb/100 ft2, about 17 lb/100 ft2, about 30 lb/100 ft2, after hot roll at 150° F. For example, the drilling fluid can have a yield point of about 4 lb/100 ft2 to about 7 lb/100 ft2, about 5 lb/100 ft2 to about 10 lb/100 ft2, about 6 lb/100 ft2 to about 17 lb/100 ft2, about 8 lb/100 ft2 to about 15 lb/100 ft2, or about 8 lb/100 ft2 to about 28 lb/100 ft2, after hot roll at 150° F. The drilling fluid containing the emulsifier can have higher electrical stability.\",\n \"The drilling fluid containing the emulsifier can have an electrical stability of about 600 V, about 700 V, or about 725 V to about 800 V, about 1,000 V, or about 1,200 V, at 150° F. For example, the drilling fluid containing the emulsifier can have an electrical stability of about 600 V to about 650 V, about 650 V to about 700 V, about 675 V to about 750 V, about 700 V to about 760 V, about 725 V to about 850 V, about 825 V to about 950 V, about 925 V to about 1,100 V, or about 1,000 V to about 1,200 V, at 150° F. The drilling fluid containing the emulsifier can have high temperature/high pressure fluid loss of about 5 mL, about 6 mL, or about 7 mL to about 10 mL, about 12 mL, about 14 mL, after hot roll at 150° F. For example, the drilling fluid can have a fluid loss of about 4 mL to about 7 mL, about 5 mL to about 10 mL, about 6 mL to about 11 mL, or about 8 mL to about 14 mL, after hot roll at 150° F. The drilling fluid containing the emulsifier can exhibit minimal water break-through under high temperature/high pressure testing conditions.\",\n \"The drilling fluid containing the emulsifier can have a water break-through value of about 0 mL, about 0.1 mL, or about 0.2 mL to about 0.5 mL, at high temperature/high pressure testing conditions.\",\n \"For example, the drilling fluid containing the emulsifier can have a water break-through value of about 0 mL to about 0.1 mL, about 0.1 mL to about 0.2 mL, about 0.2 mL to about 0.3 mL, about 0.3 mL to about 0.4 mL, or about 0.4 mL to about 0.5 mL, at high temperature/high pressure testing conditions.\",\n \"The compounds of Formula (I) can be made using one or more different synthetic routes.\",\n \"One exemplary synthetic route can include sequential condensation reactions as shown in Scheme (I) below.\",\n \"More particularly, a polyamine can be reacted with fatty acids to produce an amidoamine product.\",\n \"The amidoamine product can be reacted with a succinic anhydride to produce a triamide.\",\n \"In the specific embodiment depicted in Scheme (I), two molecules of the same kind of fatty acid are reacted with diethylenetriamine as the polyamine to form a diamidoamine or “intermediate product.” In a subsequent condensation reaction, the diamidoamine is reacted with succinic anhydride as the saturated dicarboxylic acid to produce a triamide.\",\n \"Exemplary Scheme (I) is as follows: It can be seen that the triamide depicted in Scheme (I) has the molecular structure of Formula (I), where R1 and R4 are the same.\",\n \"The reaction conditions, e.g., heating, can be controlled to favor the more thermodynamically stable amide product.\",\n \"Any of the amine functional groups on the polyamine can undergo a condensation reaction with the carboxylic acid group of the fatty acid; however, the primary amines can be more kinetically favored than the secondary amines on the polyamine.\",\n \"By controlling the reaction conditions, such as the concentration of the reactants, the reaction of one fatty acid molecule for every primary amine on the polyamine can be favored.\",\n \"A thermodynamically and kinetically favored diamidoamine has been depicted in Reaction 1 of Scheme (I).\",\n \"The diamidoamine can then be reacted with a saturated dicarboxylic acid and/or a saturated acid anhydride.\",\n \"Reaction 2 of Scheme (I) depicts a condensation reaction between the diamidoamine and succinic anhydride.\",\n \"At least one of the acyl moieties on the succinic anhydride can react with at least one of the secondary amine functional groups on the diamidoamine (for diethylenetriamine only one secondary amine is present) to form a third amide group.\",\n \"The second acyl moiety on the anhydride can react with a second diamidoamine in the reaction mixture, e.g., two diamidoamine molecules can react with one anhydride compound.\",\n \"By controlling the reaction conditions, however, such as the concentrations of the reactants, the reaction between one diamidoamine molecule and one dicarboxylic acid or acid anhydride molecule can be favored.\",\n \"Also, if the reaction is performed with an acid anhydride compound instead of a dicarboxylic acid compound, a lower temperature can be used, which leads to less cross-linking between diamidoamines.\",\n \"In one or more examples, the reaction product can be triamide, as illustrated in Reaction 2 of Scheme (I).\",\n \"In one or more examples, after a single condensation reaction of the fatty acid and the polyamine, a self-cyclization reaction can produce an imidazoline (e.g., a 1-aminoalkyl-2-alkyl-2-imidazoline).\",\n \"For clarity, Reaction 3 has been included to show an exemplary imidazoline product when the reactant polyamine is diethylenetriamine.\",\n \"The reaction mixture for the diamidoamine and, if the subsequent reaction is performed in a single pot, the reaction mixture for the triamide can also include the imidazoline product.\",\n \"The primary amine of the imidazoline product can also react with the saturated dicarboxylic acid and/or saturated acid anhydride.\",\n \"Because the imidazoline product is less effective as an emulsifier, the reaction conditions, such as reaction temperature, can be chosen to limit the imidazoline reaction product.\",\n \"Exemplary reaction conditions for limiting the imidazoline reaction product can include those discussed and described in U.S. Pat.\",\n \"No.\",\n \"3,758,493.One or more fatty acids, one or more polyamines, and one or more liquid media can be mixed to from a diamidoamine reaction mixture.\",\n \"The molar ratio of the carboxylic acid group on the fatty acid to the primary amine groups on the polyamine can be used to favor a reaction between one fatty acid molecule for every primary amine group on the polyamine.\",\n \"For example, e molar ratio of the carboxylic acid group to the primary amine group can be about 0.5:1 to about 1.1:1.In another example, the molar ratio of the carboxylic acid group to the primary amine group can be about 0.5:1 to about 0.7:1, about 0.6:1 to about 0.8:1, about 0.7:1 to about 1:1, about 0.9:1 to about 1:1, or about 0.8:1 to about 1.1:1.The diamidoamine reaction mixture can be heated to a temperature of about 130° C., about 140° C., about 145° C. to about 170° C., about 180° C., or about 200° C. For example, the reaction temperature can be about 140° C. to about 150° C., about 145° C. to about 155° C., about 155° C. to about 165° C., about 160° C. to about 170° C., about 155° C. to about 170° C., about 160° C. to about 190° C., or about 180° C. to about 200° C. The diamidoamine reaction mixture of the fatty acids and the polyamine can be heated for, or otherwise have a reaction time of, about 0.5 hours, about 1 hour, about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6 hours, about 7 hours, about 8 hours, about 9 hours, about 10 hours, about 11 hours, about 12 hours, or greater.\",\n \"For example, the fatty acids and the polyamine can be heated or reacted for about 0.7 hours to about 1.3 hours, about 0.7 hours to about 1.3 hours, about 1 hour to about 3 hours, about 1.5 hours to about 4 hours, about 2 hours to about 5 hours, about 3 hours to about 7 hours, about 5 hours to about 8 hours, about 6 hours to about 10 hours, about 8 hours to about 12 hours.\",\n \"The fatty acids and the polyamine can be reacted until a desired acid value is obtained.\",\n \"The diamidoamine reaction mixture can have an acid value of about 3 mg of KOH, about 5 mg of KOH, or about 7 mg of KOH to about 15 mg of KOH, about 20 mg of KOH, or about 25 mg of KOH, per gram of diamidoamine reaction mixture.\",\n \"For example, the diamidoamine reaction mixture can have an acid value of about 3 mg of KOH to about 5 mg of KOH, about 4 mg of KOH to about 8 mg of KOH, about 7 mg of KOH to about 12 mg of KOH, about 9 mg of KOH to about 15 mg of KOH, about 10 mg of KOH to about 16 mg of KOH, about 14 mg of KOH to about 20 mg of KOH, about 16 mg of KOH to about 25 mg of KOH, per gram of diamidoamine reaction mixture.\",\n \"The diamidoamine reaction mixture can include a solvent or diluent, also referred to as “liquid medium.” The diamidoamine reaction can also be performed neat so the diamidoamine reaction mixture can be free of solvent or liquid medium.\",\n \"The diamidoamine reaction mixture can have a liquid medium concentration of about 0.1 wt %, about 1 wt %, or about 3 wt % to about 10 wt %, about 15 wt %, or about 20 wt %, based on the combined weight of the fatty acids, the polyamines, and the liquid medium.\",\n \"In another example, the diamidoamine reaction mixture can have a liquid medium concentration of about 0.1 wt % to about 3 wt %, about 0.1 wt % to about 4 wt %, about 1 wt % to about 6 wt %, about 3 wt % to about 8 wt %, about 7 wt % to about 14 wt %, about 11 wt % to about 17 wt %, or about 12 wt % to about 20 wt %, the polyamines, and the liquid medium.\",\n \"During the reaction, the liquid medium can be distilled or evaporated from the diamidoamine reaction mixture, which can change the concentration of the liquid medium.\",\n \"The diamidoamine reaction mixture can have a solids content of about 80 wt %, about 85 wt %, or about 90 wt % to about 95 wt %, about 98 wt %, or about 100 wt % (e.g., where the solvent-free system has 100 wt % solids), based on the total weight of the reaction mixture.\",\n \"In another example, the diamidoamine reaction mixture can have a solids content of about 80 wt % to about 85 wt %, about 85 wt % to about 90 wt %, about 90 wt % to about 95 wt %, about 94 wt % to about 98 wt %, about 96 wt % to about 99 wt %, or about 96 wt % to about 100 wt %, based on the total weight of the reaction mixture.\",\n \"As used herein, the solids content, as understood by those skilled in the art, can be measured by determining the weight loss upon heating a small sample (e.g., about 1 gram to about 5 grams) of the reaction mixture, to a suitable temperature, e.g., about 125° C., and a time sufficient to remove the liquid therefrom.\",\n \"Illustrative fatty acids that can be reacted with the polyamine to form the diamidoamine can include, but are not limited to, the alkanoic and alkenoic fatty acids having from about 6 carbon atoms to about 24 carbon atoms, such as lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, oleic acid, linoleic acid, erucic acid, or any combination thereof Mixtures of fatty acids can also be used.\",\n \"Illustrative fatty acids can be provided or used in the form of crude tall oil (CTO), one or more tall oil distillation products, one or more vegetable oils, and any mixture thereof.\",\n \"In one embodiment, crude tall oil can be made or produced as an acidified byproduct in the kraft or sulfate processing of wood.\",\n \"Crude tall oil, prior to refining, can include a mixture of rosin acids, fatty acids, sterols, high-molecular weight alcohols, and other alkyl chain materials.\",\n \"The components of crude tall oil depend on a variety of factors, such as the particular coniferous species of the wood being processed (wood type), the geographical location of the wood source, the age of the wood, the particular season that the wood is harvested, and others.\",\n \"Thus, depending on the particular source, crude tall oil can contain about 20 wt % to about 75 wt % of fatty acids (e.g., about 30 wt % to about 60 wt % of fatty acids), about 20 wt % to about 65 wt % of rosin acids and the balance being the neutral and non-saponifiable components.\",\n \"Crude tall oil can contain at least 10 wt % of neutral materials or non-saponifiable components.\",\n \"Distillation of crude tall oil can be used to recover a mixture of fatty acids in the C16-C20 range.\",\n \"Fatty acids found in tall oils can include, but are not limited to, oleic acid, linoleic acid, stearic acid, and palmitic acid.\",\n \"Rosin acids found in tall oils, include, but are not limited to, abietic acid, dehydroabietic acid, isopimaric acid, and pimaric acid.\",\n \"Examples of tall oil distillation products that can be used as the fatty acids or at to make up at least a portion of the fatty acids discussed and described herein can include, but are not limited to, tall oil fatty acids (TOFA), distilled tall oil (DTO), tall oil pitch, or any mixture thereof.\",\n \"The distilled tall oil fraction can have a fatty acids and esters of fatty acids concentration of about 55 wt %, about 60 wt %, or about 65 wt % to about 85 wt %, about 90 wt %, or about 95 wt %.\",\n \"The distilled tall oil fraction can have a rosin acids or rosins concentration of about 5 wt %, about 10 wt %, or about 15 wt % to about 30 wt %, about 35 wt %, or about 40 wt %.\",\n \"The distilled tall oil fraction can have a neutrals concentration of about 0.1 wt %, about 1 wt %, or about 1.5 wt % to about 2 wt %, about 3.5 wt %, or about 5 wt %.\",\n \"The distilled tall oil fraction can have an acid value of about 20, about 25, or about 30 to about 40, about 45, or about 50.The distilled tall oil fraction can have a viscosity (centipoise at 85° C.) of about 10 cP, about 20 cP, about 30 cP, or about 40 cP to about 100 cP, about 120 cP, about 135 cP, or about 150 cP.\",\n \"The distilled tall oil can have a density of about 840 g/L, about 860 g/L, or about 880 g/L to about 900 g/L, about 920 g/L, or about 935 g/L.\",\n \"The distilled tall oil fraction can have a saponification number of about 180, about 185, or about 190 to about 200, about 205, or about 210.The distilled tall oil fraction can have an iodine value of about 115, about 117, or about 120 to about 130, about 135, or about 140.The rosin acids derived from crude tall oil are also an intermediate fraction that can be produced from the distillation of crude tall oil.\",\n \"The tall oil rosin can have a concentration of rosin acids of about 80 wt %, about 85 wt %, or about 90 wt % to about 93 wt %, about 95 wt %, or about 99 wt %.\",\n \"The tall oil rosin can have a concentration of abietic acid of about 35 wt %, about 40 wt %, or about 43 wt % to about 50 wt %, about 55 wt %, or about 60 wt %.\",\n \"The tall oil rosin can have a concentration of dehydroabietic acid of about 10 wt %, about 13 wt %, or about 15 wt % to about 20 wt %, about 23 wt %, or about 25 wt %.\",\n \"The tall oil rosin can have a concentration of isopimaric acid of about 10 wt % or less, about 8 wt % or less, about 5 wt % or less, or about 3 wt % or less.\",\n \"The tall oil rosin can have a concentration of pimaric acid of about 10 wt % or less, about 8 wt % or less, about 5 wt % or less, or about 3 wt % or less.\",\n \"The tall oil rosin can have a fatty acids concentration of about 0.5 wt %, about 1 wt %, or about 2 wt % to about 3 wt %, about 5 wt %, or about 10 wt %.\",\n \"The tall oil rosin can have a concentration of neutral materials of about 0.5 wt %, about 1 wt %, or about 2 wt % to about 3 wt %, about 5 wt %, or about 10 wt %.\",\n \"The tall oil rosin can have a density of about 960 g/L, about 970 g/L, or about 980 g/L to about 1,000 g/L, about 1,010 g/L, or about 1,020 g/L.\",\n \"The tall oil rosin can have an acid value of about 150, about 160, or about 165 to about 170, about 175, or about 180.Representative tall oil products can include saturated and unsaturated fatty acids in the C16-C18 range, as well as minor amounts of rosin acids, and can include XTOL® 100, XTOL® 300, and XTOL® 304, XTOL® 520, and LYTOR® 100, all of which are commercially available from Georgia-Pacific Chemicals LLC, Atlanta, Ga. XTOL® 100 includes about 1.6 wt % of palmitic acid, about 2.5 wt % of stearic acid, about 37.9 wt % of oleic acid, about 26.3 wt % of linoleic acid, about 0.3 wt % of linolenic acid, about 2.9 wt % of linoleic isomers, about 0.2 wt % of arachidic acid, about 3.6 wt % eicosatrienoic acid, about 1.4 wt % of pimaric acid, <0.16 wt % of sandarocopimaric, <0.16 wt % of isopimaric acid, <0.16 wt % of dehydroabietic acid, about 0.2 wt % of abietic acid, with the balance being neutrals and high molecular weight species.\",\n \"LYTOR® 100 includes <0.16 wt % of palmitic acid, <0.16 wt % of stearic acid, about 0.2 wt % of oleic acid, about 0.2 wt % of arachidic acid, about 0.2 wt % eicosatrienoic acid, about 2.2 wt % of pimaric acid, about 0.6 wt % of sandarocopimaric, about 8.5 wt % of palustric acid, about 1.6 wt % of levopimaric acid, about 2.8 wt % of isopimaric acid, about 15.3 wt % of dehydroabietic acid, about 51.4 wt % of abietic acid, about 2.4 wt % of neoabietic acid, with the balance being neutrals and high molecular weight species.\",\n \"XTOL® 520 DTO includes about 0.2 wt % of palmitic acid, about 3.3 wt % of stearic acid, about 37.9 wt % of oleic acid, about 26.3 wt % of linoleic acid, about 0.3 wt % of linolenic acid, about 2.9 wt % of linoleic isomers, about 0.2 wt % of arachidic acid, about 3.6 wt % eicosatrienoic acid, about 1.4 wt % of pimaric acid, <0.16 wt % wt % of sandarocopimaric, <0.16 wt % of isopimaric acid, <0.16 wt % of dehydroabietic acid, about 0.2 wt % of abietic acid, with the balance being neutrals and high molecular weight species.\",\n \"Such tall oil products can be used in the reaction with the polyamine or a mixture of polyamines.\",\n \"Other fatty acids and mixtures of fatty acids, including oxidized and/or dimerized tall oil, such those discussed below can also be employed.\",\n \"Illustrative vegetable oils that can be used as the fatty acids can include, but are not limited to, safflower oil, grapeseed oil, sunflower oil, walnut oil, soybean oil, cottonseed oil, coconut oil, corn oil, olive oil, palm oil, palm olein, peanut oil, rapeseed oil, canola oil, sesame oil, hazelnut oil, almond oil, beech nut oil, cashew oil, macadamia oil, mongongo nut oil, pecan oil, pine nut oil, pistachio oil, grapefruit seed oil, lemon oil, orange oil, watermelon seed oil, bitter gourd oil, buffalo gourd oil, butternut squash seed oil, egusi seed oil, pumpkin seed oil, borage seed oil, blackcurrant seed oil, evening primrose oil, açaaí oil, black seed oil, flaxseed oil, carob pod oil, amaranth oil, apricot oil, apple seed oil, argan oil, avocado oil, babassu oil, ben oil, borneo tallow nut oil, cape chestnut, algaroba oil, cocoa butter, cocklebur oil, poppyseed oil, cohune oil, coriander seed oil, date seed oil, dika oil, false flax oil, hemp oil, kapok seed oil, kenaf seed oil, lallemantia oil, mafura oil, manila oil, meadowfoam seed oil, mustard oil, okra seed oil, papaya seed oil, perilla seed oil, persimmon seed oil, pequi oil, pili nut oil, pomegranate seed oil, prune kernel oil, quinoa oil, ramtil oil, rice bran oil, royle oil, shea nut oil, sacha inchi oil, sapote oil, seje oil, taramira oil, tea seed oil, thistle oil, tigernut oil, tobacco seed oil, tomato seed oil, wheat germ oil, castor oil, colza oil, flax oil, radish oil, salicornia oil, tung oil, honge oil, jatropha oil, jojoba oil, nahor oil, paradise oil, petroleum nut oil, dammar oil, linseed oil, stillingia oil, vernonia oil, amur cork tree fruit oil, artichoke oil, balanos oil, bladderpod oil, brucea javanica oil, burdock oil, candlenut oil, carrot seed oil, chaulmoogra oil, crambe oil, croton oil, cuphea oil, honesty oil, mango oil, neem oil, oojon oil, rose hip seed oil, rubber seed oil, sea buckthorn oil, sea rocket seed oil, snowball seed oil, tall oil, tamanu oil, tonka bean oil, ucuhuba seed oil, or any mixture thereof.\",\n \"If the fatty acid includes two or more fatty acids, each fatty acid can be present in the same concentration or different concentrations with respect to one another.\",\n \"For example, a first fatty acid can be present in a weight ratio of about 99:1, about 90:10, about 80:20, about 70:30, about 60:40, about 50:50, about 40:60, about 30:70, about 20:80, about 10:90, or about 1:99 with respect to another or “second” fatty acid contained therein.\",\n \"Similarly, if three or more fatty acids are mixed, the three or more fatty acids can be present in any ratio.\",\n \"The polyamine reacted with the one or more fatty acids to produce the diamidoamine can include, but is not limited to, one or more compounds having the general chemical formal, Formula (II): H2N[(CH2)xNH]yH (II) where x and y can be integers independently selected from 1 to 10.Representative polyamines include the polyethylene polyamines, when x is 2.Of this class of polyalkylene polyamines, specific examples can include, dimethylenetriamine (x=1, y=2), diethylenetriamine (x=2, y=2), triethylenetetramine (x=2, y=3), tripropylenetetramine (x=3, y=3) tetraethylenepentamine (x=2, y=4), and pentaethylenehexamine (x=2, y=5).\",\n \"The polyamine can be or include a mixture of two or more polyamines.\",\n \"If the polyamines include two or more polyamines, each polyamine can be present in the same concentration or different concentrations with respect to one another.\",\n \"For example, a first polyamines can be present in a weight ratio of about 99:1, about 90:10, about 80:20, about 70:30, about 60:40, about 50:50, about 40:60, about 30:70, about 20:80, about 10:90, or about 1:99 with respect to another or “second” polyamine contained therein.\",\n \"Similarly, if three or more polyamines are mixed, the three or more polyamines can be present in any ratio.\",\n \"The liquid medium, if present, can be or include water.\",\n \"The water can be added or generated during the condensation reactions or both.\",\n \"The liquid medium can also be or include one or more polar aprotic solvents, one or more polar protic solvents, or any combination thereof.\",\n \"Illustrative polar aprotic solvents can include, but are not limited to, tetrahydrofuran (“THF”), dimethyl sulfoxide (“DMSO”), N-methylpyrrolidone (“NMP”), dimethyl acetamide, acetone, or any combination thereof.\",\n \"Illustrative polar protic solvents can include, but are not limited to, methanol, ethanol, propanol, butanol, or any combination thereof.\",\n \"One or more diamidoamines, one or more liquid media, and the saturated dicarboxylic acid and/or the saturated acid anhydride can be mixed to form a triamide reaction mixture.\",\n \"The diamidoamine, the liquid media, and the saturated dicarboxylic acid and/or saturated acid anhydride can be combined with one another in any order or sequence.\",\n \"The diamidoamine can be isolated from the diamidoamine reaction mixture and then mixed with the liquid medium and the saturated dicarboxylic acid and/or the saturated acid anhydride to make the triamide reaction mixture.\",\n \"Or, the liquid medium and the saturated dicarboxylic acid and/or the saturated acid anhydride can be mixed with the diamidoamine reaction mixture to make the triamide reaction for a one pot synthesis.\",\n \"The molar ratio of the carboxylic acid groups on the saturated dicarboxylic acid to the secondary amine groups on the diamidoamine can be used to favor the reaction product between one saturated dicarboxylic acid molecule and one diamidoamine molecule.\",\n \"For example, the molar ratio of carboxylic acid groups to secondary amine groups can be about 0.4:1, about 0.5:1, or about 0.7:1 to about 0.9:1, about, 1.0:1, or about 1.2:1.In another example, the molar ratio of the carboxylic acid groups to secondary amine groups can be about 0.4:1 to about 0.6:1, about 0.5:1 to about 0.7:1, about 0.7:1 to about 0.9:1, about 0.8:1 to about 1.1:1, about 0.9:1 to about 1:1, about 0.9:1 to about 1.1:1, or about 0.9:1 to about 1.2:1.The molar ratio of the anhydride group on the saturated acid anhydride to the secondary amine groups on the diamidoamine can be used to favor the reaction product between one saturated acid anhydride molecule and one diamidoamine molecule.\",\n \"For example, the molar ratio of the anhydride group to the secondary amine groups can be about 0.2:1, about 0.4:1, or about 0.6:1 to about 0.8:1, about 0.9:1, or about 1:1.In another example, the molar ratio of the anhydride group to the secondary amine groups can be about 0.2:1 to about 1:1, about 0.4:1 to about 0.9:1, about 0.75:1 to about 0.85:1, or about 0.78:1 to about 0.82:1.The reaction between the diamidoamine and the saturated dicarboxylic acid or the saturated anhydride can be at a temperature of about 25° C., about 40° C., or about 60° C. to about 130° C. about 150° C. or about 175° C. For example, the reaction temperature can be about 30° C. to about 60° C., about 55° C. to about 85° C., about 60° C. to about 80° C., about 70° C. to about 90° C., about 70° C. to about 80° C., about 73° C. to about 95° C., about 92° C. to about 130° C., about 120° C. to about 160° C., and about 160° C. to about 200° C. Relative to the use of the saturated acid anhydride, the use of the saturated dicarboxylic acid to react the terminal amine groups of the fatty acid amine condensate to terminal carboxylic acid groups often requires higher reaction temperatures.\",\n \"The reaction time for the reaction between the diamidoamine and the saturated dicarboxylic acid or the saturated anhydride can be about 0.2 hours, about 0.4, or about 0.5 to about 1 hour, about 1.5 hours or about 2 hours.\",\n \"For example, the reaction time can be about 0.2 hours to about 0.6 hours, about 0.5 hours to about 1 hour, about 0.6 hours to about 0.8 hours, about 0.7 hours to about 1 hour, about 1 hour to about 1.5 hours, about 1 hour to about 1.2 hours, or about 1 hour to about 2 hours.\",\n \"Relative to the use of a saturated acid anhydride, the use of a saturated dicarboxylic acid to convert the secondary amine groups to the amide groups often requires longer reaction times.\",\n \"The diamidoamine and the saturated dicarboxylic acid or the saturated anhydride can be reacted until a desired acid value is obtained.\",\n \"The acid value of the triamide reaction mixture can be about 20 mg of KOH, about 30 mg of KOH, or about 40 mg of KOH to about 80 mg of KOH, about 90 mg of KOH, or about 100 mg of KOH, per gram of triamide reaction mixture.\",\n \"For example, the triamide reaction mixture can have an acid value of about 25 mg of KOH to about 35 mg of KOH, about 30 mg of KOH to about 50 mg of KOH, about 50 mg of KOH to about 70 mg of KOH, about 55 mg of KOH to about 65 mg of KOH, about 60 mg of KOH to about 90 mg of KOH, about 80 mg of KOH to about 100 mg of KOH, per gram of triamide reaction mixture.\",\n \"The acid value can be used as a measure of the amount of carboxylic acid groups in the triamide reaction mixture.\",\n \"The triamide reaction mixture can include a solvent or diluent or “liquid medium.” Suitable liquid mediums can be or include those liquid mediums discussed and described above with reference to the diamidoamine reaction mixture.\",\n \"The triamide reaction can also be performed neat so the triamide reaction mixture can be free of solvent or liquid medium.\",\n \"The triamide reaction mixture can have a liquid medium concentration of about 0 wt %, about 1 wt %, or about 3 wt % to about 10 wt %, about 15 wt %, or about 20 wt %, based on the combined weight of the diamidoamine, the liquid medium, and the saturated dicarboxylic acid and/or the saturated acid anhydride.\",\n \"In another example, the diamidoamine reaction mixture can have a liquid medium concentration of about 0 wt % to about 3 wt %, about 0.1 wt % to about 4 wt %, about 1 wt % to about 6 wt %, about 3 wt % to about 8 wt %, about 7 wt % to about 14 wt %, about 11 wt % to about 17 wt %, or about 12 wt % to about 20 wt %, based on the combined weight of the diamidoamine, the liquid medium, and the saturated dicarboxylic acid and/or the saturated acid anhydride.\",\n \"During the reaction, the liquid medium can be distilled, evaporated, or otherwise separated from the triamide reaction mixture, which can change the concentration of the liquid medium.\",\n \"The triamide reaction mixture can have a viscosity of about 55 cP, about 100 cP, or about 150 cP to about 2,000 cP, about 3,000 cP, or about 5,000 cP, at 90° C. For example, the viscosity of the triamide reaction mixture can have a viscosity of about 65 cP to about 105 cP, about 100 cP to about 500 cP, about 400 cP to about 1,000 cP, about 900 cP to about 1,200 cP, about 1,000 cP to about 1,500 cP, about 1,300 cP to about 1,600 cP, about 1,500 cP to about 2,000 cP, about 1,800 cP to about 2,600 cP, about 2,000 cP to about 3,000, about 2,500 cP to about 4,000, about 3,000 cP to about 5,000, at 90° C. The viscosity can be used to characterize the reaction product.\",\n \"The viscosity can be determined using a Brookfield viscometer.\",\n \"The viscometer measures the torque required to rotate a spindle at constant speed in a solution of a diamidoamine reaction mixture at 25° C. Standard test methods used for measuring Brookfield viscosity are ASTM D 803-03 and AOCS Ja 10-87 (93).\",\n \"The triamide reaction mixture can have a solids content of about 80 wt %, about 85 wt %, or about 90 wt % to about 95 wt %, about 98 wt %, or about 100 wt % (e.g., where the solvent- free system has 100 wt % solids), based on the total weight of the triamide reaction mixture.\",\n \"In another example, the diamidoamine reaction mixture can have a solids content of about 80 wt % to about 85 wt %, about 85 wt % to about 90 wt %, about 90 wt % to about 95 wt %, about 94 wt % to about 98 wt %, about 96 wt % to about 99 wt %, or about 96 wt % to about 100 wt %, based on the total weight of the triamide reaction mixture.\",\n \"During the reaction, water from the condensation between the diamidoamine and the saturated dicarboxylic acid or the saturated acid anhydride can be distilled from the triamide reaction mixture, which can change the solids content.\",\n \"Representative saturated dicarboxylic acids can include, but are not limited to, succinic acid, adipic acid, malic acid, and glutaric acid and the like.\",\n \"Representative saturated acid anhydrides can include, but are not limited to, succinic anhydride, adipic anhydride, and glutaric anhydride.\",\n \"The triamide can be at least partially isolated from triamide reaction mixture or the triamide reaction mixture can be mixed with the tall oil without further processing.\",\n \"The triamide and the tall oil can be combined with one another in any order or sequence.\",\n \"Illustrative tall oils can include, but are not limited to, crude tall oil, distilled tall oil, tall oil bottoms, a dimerized tall oil, a Diels-Alder reaction product and/or an ene reaction product of tall oil with an one or more α,β unsaturated carboxylic acids or acid anhydrides, a Diels-Alder reaction product and/or an ene reaction product of tall oil with an one or more α,β unsaturated carboxylic acids or acid anhydrides that has also been dimerized, or any mixture thereof.\",\n \"Representative tall oil distillate components include tall oil fatty acids, tall oil rosin acids, and mixtures of these fractions.\",\n \"As mentioned above, the refinement (e.g., fractionation) of tall oil can, for example, provide C16-C18 saturated and unsaturated fatty acids as well as fatty acid/rosin acid mixtures.\",\n \"Mixtures of tall oil distillate fractions can also be employed as the tall oil distillate component.\",\n \"Fatty acid and rosin acid mixtures in any desired ratio can be obtained in a single distillate fraction by adjusting tall oil fractionation conditions.\",\n \"Representative tall oil distillate components include XTOL® 100, XTOL® 300, and XTOL® 304, XTOL® 520, and LYTOR® 100, all commercially available from Georgia-Pacific Chemicals LLC, Atlanta, Ga.\",\n \"In one specific embodiment, a mixture of a first tall oil distillate fraction comprising predominantly fatty acids (e.g., XTOL® 100) and a second tall oil distillate fraction comprising predominantly rosin acids (e.g., LYTOR® 100) can be mixed in any proportion.\",\n \"In such a mixture, representative amounts of fatty acids and rosin acids can be about 45 wt % to about 90 wt % and about 10 wt % to about 55 wt %, respectively.\",\n \"The mixing ratios of the first tall oil distillate fraction to second tall oil distillate fraction can be in a weight ratio of about 9:1, about 4:1, about 7:3, about 3:2, about 1:1, about 2:3, about 3:7, about 1:4, or about 1:9.Depending on the crude tall oil composition and fractionation conditions, a single tall oil distillate fraction can also suffice to yield a composition that is substantially the same as any of the mixes of tall oil distillate fractions discussed above.\",\n \"The α,β unsaturated carboxylic acids or acid anhydrides can react with tall oil via the ene reaction or a Diels-Alder reaction on the tall oil fatty acids and/or the rosin acids in the tall oil.\",\n \"The modified tall oil product generated from the reaction of tall oil with the specific α,β unsaturated anhydride, maleic anhydride, can be referred to as a “maleated tall oil,” which includes “maleated fatty acids” and “maleated rosin acids.” Non-limiting examples of representative reactions that can occur can include those discussed and described in U.S. Pat.\",\n \"Nos.\",\n \": 4,927,669; 8,133,970; and 8,334,363.The ene reaction and the Diels-Alder reaction are explained in further detail in Jerry March & Michael B. Smith, MARCH'S ADVANCED ORGANIC CHEMISTRY: REACTIONS, MECHANISMS, AND STRUCTURE (7th ed.\",\n \"John Wiley & Sons Inc. 2013) (1985).\",\n \"The amount of α,β unsaturated carboxylic acid or acid anhydride reacted with the tall oil can vary based, at least in part, on the specific tall oil product to be reacted.\",\n \"Suitable amounts of the carboxylic acid and/or acid anhydride reacted with the tall oil can be about 1 wt %, about 2 wt %, about 3 wt %, about 5 wt %, about 10 wt %, or about 15 wt % to about 30 wt %, about 35 wt %, about 40 wt %, about 45 wt %, or about 50 wt %, based on the combined weight of the tall oil and the carboxylic acid and/or acid anhydride the desired amount of the Diels-Alder product and/or the ene product.\",\n \"The tall oil can have the tall oil substituted with the α,β unsaturated carboxylic acids or acid anhydrides in an amount of about 1 wt %, about 3 wt %, or about 5 wt % to about 20 wt %, about 25 wt %, or about 30 wt %, based on the total weight of tall oil.\",\n \"For example, the tall oil can have the tall oil substituted with the α,β unsaturated carboxylic acids or acid anhydrides in an amount of about 2 wt % to about 7 wt %, about 5 wt % to about 10 wt %, about 10 wt % to about 20 wt %, about 18 wt % to about 22 wt %, about 20 wt % to about 27 wt %, based on the total weight of tall oil.\",\n \"The reaction of tall oil and the α,β unsaturated carboxylic acids or acid anhydrides, can be performed at a reaction temperature of about 150° C. to about 250° C., about 200° C. to about 230° C., or about 215° C. to about 225° C. The reaction can be quenched after a reaction time of about 12 hours, about 16 hours, about 20 hours, about 22 hours, about 26 hours, about 30 hours, about 34 hours, about 38 hours, or greater.\",\n \"For example, the reaction time can be about 12 hours to about 36 hours or about 20 hours to about 30 hours.\",\n \"The dimerized tall oil can be obtained by catalytic dimerization of the tall oil fatty acids or by the oxidation of tall oil to provide an ether bond linking the fatty acid's hydrocarbon chain.\",\n \"In an embodiment, the catalytic dimerization can be clay catalyzed Diels-Alder type reaction that links at least two hydrocarbon chains of the tall oil fatty acids through a carbon-carbon bond.\",\n \"In another embodiment, tall oil can be oxidized by heating the tall oil material to a temperature of at least 150° C. For example, the tall oil can be heated to a temperature of about 155° C., about 160° C., or about 165° C. to about 170° C., about 180° C., about 190° C., about 200° C., or about 225° C., in the presence of an oxidant.\",\n \"In at least one specific example, the tall oil can be heated to a temperature of about 160° C. to about 170° C., followed by contacting the heated tall oil composition with oxygen or air.\",\n \"For example, the tall oil can be heated to a temperature of about 160° C. to about 170° C., followed by sparging oxygen or air through the heated tall oil composition.\",\n \"As understood by those skilled in the art, a variety of techniques and devices can advantageously be used to contact the heated tall oil with the oxygen or air and the present method is not limited to any specific technique or equipment.\",\n \"The hydrocarbon chains can be fatty acids and rosin acids.\",\n \"The hydrocarbon chains can be, for example, C6-C22 fatty acids.\",\n \"The hydrocarbon chains can be, for example, C16-C22 fatty acids.\",\n \"The hydrocarbon chains can be, for example, C16-C18 fatty acids.\",\n \"The hydrocarbon chains can be, for example, a C18 fatty acid.\",\n \"The hydrocarbon chains can be, for example, oleic acid, linoleic acid, and linolenic acid.\",\n \"Illustrative Diels-Alder reaction product and/or an ene reaction product of tall oil with an one or more α,β unsaturated carboxylic acids or acid anhydrides and illustrative Diels-Alder reaction product and/or an ene reaction product of tall oil with one or more α,β unsaturated carboxylic acids or acid anhydrides that has also been dimerized can include those compositions discussed and described in U.S. Patent Application Publication Nos.\",\n \"2008/0179570, 2008/0194795, 2009/0065736, and 2009/0194731.The emulsifier can be neutralized (e.g., converted to its corresponding alkali or alkaline earth metal salt) before spray drying.\",\n \"The emulsifier used to form the spray dried emulsifier, namely the triamide and the tall oil, is acidic prior to neutralization.\",\n \"In the case of the triamide, acidity results from the installation of a carboxylic acid group from the condensation reaction of the diamidoamine to the saturated dicarboxylic acid and/or acid anhydride.\",\n \"In the case of the tall oil, acidity also results from the addition of the unsaturated dicarboxylic acid and/or unsaturated acid anhydride functionality (e.g., in the Diels-Alder reaction or the ene reaction with tall oil fatty acids and/or tall oil rosin acids).\",\n \"These acidic components can be neutralized (or saponified) by the addition of a suitable base.\",\n \"Neutralization with an alkali metal hydroxide, an alkaline earth metal hydroxide, an alkali metal oxide, an alkaline earth metal oxide, or any mixture of these bases can result in the conversion of the triamide and the tall oil to their corresponding alkali metal salts and/or alkaline earth metal salts (e.g., carboxylate salts).\",\n \"For example, the carboxylic acid of the triamide can be reacted with any of these bases to form metal carboxylate groups (e.g., sodium carboxylate groups).\",\n \"Suitable bases within the classes given above include the hydroxides and oxides of lithium, sodium, potassium, and calcium.\",\n \"Compared to the oxides, the hydroxides of these metals can provide a faster and more efficient neutralization.\",\n \"Bases can be added in either a solid form or as a solution, e.g., an aqueous solution.\",\n \"Representative aqueous solutions can include, but are not limited to, about 25 wt % to about 75 wt % of sodium hydroxide or calcium hydroxide.\",\n \"Mixtures of the above bases can also be used via a simultaneous neutralization reaction, although sequential reaction using different bases in series can also be employed.\",\n \"The amount of base required for neutralization the emulsifier can be determined from a stoichiometric determination or otherwise from direct analysis/monitoring of the acid value prior to and/or during neutralization.\",\n \"The acid value (in mg KOH/g required for neutralization) can be measured, for example, using ASTM D1980-87.The base can be added gradually over a period of time of about 10 minutes to about 2 hours to reduce or avoid significant temperature deviations due to the heat release upon neutralization.\",\n \"Gradual addition is also suitable in view of the low initial aqueous solubility of the triamide and/or the tall oil, prior to saponification.\",\n \"The acid value of the neutralized emulsifier can be about 0 mg of KOH, about 1 mg of KOH, or about 2 mg of KOH to about 8 mg of KOH, about 10 mg of KOH, or about 12 mg of, per gram of emulsifier.\",\n \"For example, the emulsifier can have an acid value of about 0 mg of KOH to about 2 mg of KOH, about 1 mg of KOH to about 3 mg of KOH, about 1 mg of KOH to about 5 mg of KOH, about 2 mg of KOH to about 8 mg of KOH, about 9 mg of KOH to about 12 mg of KOH, per gram of emulsifier.\",\n \"The neutralized emulsifier can have a pH of about 7, about 8, about 9, about 10, about 11, or about 11.5.For example, the neutralized emulsifier can have a pH of about 7.5 to about 8.5, about 8 to about 10, about 9 to about 11, about 9 to about 11.5, or about 8 to about 9.5.Neutralization with a base can be carried out at a temperature of about 50° C., about 55° C., or about 60° C. to about 85° C., about 90° C., or about 100° C. For example, neutralization can be performed at a temperature of about 60° C. to about 80, about 60° C., about 60° C. to about 75° C., about 65° C. to about 80° C., or about 75° C. to about 100° C. The emulsifier can be spray dried to produce a spray dried emulsifier.\",\n \"An aqueous diluent can be added to the emulsifier to adjust the viscosity and the solids content.\",\n \"Prior to spray drying, the solids content of the emulsifier can be adjusted to about 35 wt %, about 40 wt %, about 45 wt %, about 50 wt %, or greater, based on the weight of the emulsifier.\",\n \"For example, the solids content of the emulsifier can be about 35 wt % to about 45 wt %, about 40 wt % to about 50 wt %, about 45 wt % to about 50 wt %, based on the weight of the emulsifier prior to spray drying.\",\n \"In some embodiments, sufficient water can be added with the base during neutralization to achieve the desired solids content.\",\n \"The emulsifier can be fed to the spray drier head, which can be heated (e.g., using natural gas) to provide a spray drier inlet temperature of about 160° C. to about 250° C. The inlet temperature (or simply the “spray drying temperature”) can be about 180° C. to about 225° C., where higher temperatures directionally allow for higher throughput of the aqueous composition to be spray dried.\",\n \"Spray drying involves atomization, using an appropriate rotary or nozzle atomizer, of this aqueous composition.\",\n \"Rotary atomization, for example, can often carried out by contacting the solution with a wheel rotating at 30,000-50,000 rpm to produce the required spray.\",\n \"Upon contact of the spray with hot air in the spray dryer chamber, the moisture can be quickly evaporated into an exhaust stream.\",\n \"The resulting solid, free flowing particles of the spray dried emulsifier discharged continuously from the bottom of the conical chamber.\",\n \"The outlet temperature of the spray drier can be about 75° C. to about 100° C. Representative spray dryers include those supplied by Niro, A/S (Soeborg, Denmark).\",\n \"The spray dried emulsifier can have small particle sizes, which can provide dispersion and solubilization of the spray dried emulsifier in drilling fluids.\",\n \"The particle size populations can fit a normal distribution with an average cross-sectional length or average particle size (e.g., average diameter for spherical particles) of less than 120 μm, less than 100 μm, or less than 80 μm.\",\n \"The average particle size of the particles can be about 10 about 20 μm, or about 30 μm to about 90 μm, about 100 μm, or about 150 μm.\",\n \"For example, the average particle size can be about 10 μm to about 30 μm, about 20 μm to about 50 μm, about 30 μm to about 75 μm, about 70 μm to about 100 μm, about 65 μm to about 85 μm, about 80 μm to about 120 μm, or about 100 μm to about 1,500 μm.\",\n \"In another example, at least 50 wt %, at least 60 wt %, at least 70 wt %, at least 80 wt %, or at least 90 wt % of emulsifier particles can have a particle size of less than 80 microns, based on the total weight of the spray dried emulsifier.\",\n \"The average cross-sectional length or average particle size of the particles can be measured with a light scattering particle size distribution analyzer, such as those manufactured by Horiba Instruments, Inc. (Irvine, Calif.).\",\n \"The spray dried emulsifier can have a bulk density of about 0.2 g/mL, about 0.3 g/mL, or about 0.4 g/mL to about 0.6 g/mL, about 0.7 g/mL, or about 0.8 g/mL.\",\n \"For example, the bulk density of the spray dried emulsifier can be about 0.2 g/mL to about 0.35 g/mL, about 0.24 g/mL to about 0.56 g/mL, about 0.3 g/mL to about 0.5 g/mL, about 0.4 g/mL to about 0.48 g/mL, or about 0.40 g/mL, to about 0.66 g/mL.\",\n \"The spray dried emulsifier can have a residual moisture content of less than 10 wt %, less than 7 wt %, less than 5 wt %, less than 3 wt %, or less than 1 wt %, based on the total weight of the spray dried emulsifier.\",\n \"For example, the spray dried emulsifier can have a residual moisture content of about 0.5 wt % to about 3 wt %, about 1 wt % to about 3 wt %, about 2 wt % to about 5 wt %, or about 3 wt % to about 7 wt %, based on the total weight of the spray dried emulsifier.\",\n \"Silica or other anti-caking or anti-clumping agents can be added to the powder.\",\n \"For example, one or more anti-caking or anti-clumping agents can be added to the spray dried emulsifier in an amount of about 0.1 wt %, about 0.2 wt %, about 0.3 wt %, or about 0.5 wt % to about 1 wt %, about 1.5 wt %, about 2 wt %, or about 3 wt %, based on the combined weight or spray dried emulsifier and the anti-clumping agent.\",\n \"Otherwise, additional drying can be used.\",\n \"The spray dried product can be free flowing and can be stored for extended periods in the absence of exposure to moisture (e.g., in vapor barrier bags) without “re-massing” or significant agglomeration of the solid particles.\",\n \"This is based on oven aging studies of the spray dried emulsifier, used to simulate extended storage at high ambient temperatures.\",\n \"The addition of water to the spray dried emulsifier will can produce or form a basic mixture, having a pH of about 8 to about 11.The drilling fluids can be prepared by mixing the spray dried emulsifier, a continuous oil-based phase (e.g., maleated tall oil), and a dispersed aqueous phase (e.g., water or an aqueous brine solution).\",\n \"The spray dried emulsifier, the continuous oil-based phase, and the dispersed aqueous phase of the drilling fluid can be mixed or otherwise combined in any order.\",\n \"For example, the spray dried emulsifier can be first dissolved in either the oil phase or the aqueous phase, and the aqueous phase can then be gradually added to the oil phase with vigorous mixing.\",\n \"The converse method (e.g., addition of the oil phase to the aqueous phase) or alternate addition of the two phases can likewise be employed.\",\n \"The drilling fluid can be subjected to high shear condition to provide an emulsion.\",\n \"Any of a wide variety of slow or high speed mixers or agitators, homogenizers, or colloid mills can be used to obtain the degree of contact between the phases, required to disperse the internal aqueous phase in the external oil phase.\",\n \"The amount of emulsifier required to produce a stable emulsion in any given application will depend on the relative proportions of the oil and aqueous phases as well as upon the chemical nature of the respective phases and the particular manner in which the emulsion is prepared.\",\n \"The drilling fluid can include the spray dried emulsifier at a concentration of about 0.2 wt %, about 0.5 wt %, about 1 wt %, about 2 wt %, about 3 wt %, about 4 wt %, about 5 wt %, about 6 wt %, about 7 wt %, about 8 wt %, about 9 wt %, about 10 wt %, or greater, based on the combined weight of the spray dried emulsifier, the oil phase, and the aqueous phase.\",\n \"For example, the drilling fluid can include the spray dried emulsifier at a concentration of about 0.2 wt % to about 1 wt %, about 0.5 wt % to about 1.5 wt %, about 1 wt % to about 3 wt %, about 2 wt % to about 5 wt %, or about 1 wt % to about 6 wt %, based on the combined weight of the spray dried emulsifier, the oil phase, and the aqueous phase.\",\n \"The drilling fluid can have an aqueous phase concentration of about 5 wt %, about 10 wt %, about 15 wt %, about 20 wt %, about 25 wt %, about 30 wt %, about 35 wt %, or about 40 wt %, based on the combined weight of the spray dried emulsifier, the oil phase, and the aqueous phase.\",\n \"For example, the drilling fluid can have an aqueous phase concentration of about 5 wt % to about 10 wt %, about 10 wt % to about 20 wt %, about 20 wt % to about 30 wt %, about 30 wt % to about 40 wt %, about 5 wt % to about 40 wt %, about 5 wt % to about 30 wt %, about 5 wt % to about 20 wt %, about 10 wt % to about 40 wt %, or about 10 wt % to about 30 wt %, based on the combined weight of the spray dried emulsifier, the oil phase, and the aqueous phase.\",\n \"The drilling fluid can have an aqueous phase concentration of about 40 wt %, about 45 wt %, about 50 wt %, about 54 wt %, about 55 wt %, about 60 wt %, about 65 wt %, about 70 wt %, about 75 wt %, about 80 wt %, about 85 wt %, about 95 wt %, based on the combined weight of the spray dried emulsifier, the oil phase, and the aqueous phase.\",\n \"For example, the drilling fluid can have an aqueous phase concentration of about 54 wt % to about 60 wt %, about 55 wt % to about 70 wt %, about 65 wt % to about 85 wt %, or about 80 wt % to about 95 wt %, based on the combined weight of the spray dried emulsifier, the oil phase, and the aqueous phase.\",\n \"The spray dried emulsifier can be compatible with any of a number of oil bases typically used in invert emulsions, including diesel oil and other hydrocarbons, such as C14-C20 paraffins, iso-paraffins, olefins, iso-olefins, aromatics, naphthalenes, and other hydrocarbon mixtures including various products of crude oil refining.\",\n \"For the aqueous phase, a brine solution is often used, with representative brine solutions containing sodium chloride, potassium chloride, magnesium chloride, calcium chloride, or any mixtures of these in amounts up to saturation of the aqueous phase.\",\n \"Salt concentrations can be about 20 wt % to about 35 wt % of the aqueous phase.\",\n \"Dissolved salts in the aqueous phase can be used, for example, to increase drilling fluid density, decrease swelling effects of aqueous matter on formation clays, and/or reduce hole enlargement caused by the dissolution of water soluble formation components.\",\n \"When the emulsion is to contain suspended solids (e.g., a clay) or other additives, these can be added after the emulsion is prepared under high shear conditions, rather than to one phase or the other.\",\n \"Additives can be introduced simultaneously or sequentially, and accompanied by continuous mixing or agitation.\",\n \"For example, a weighting material which increases the density of the drilling fluid can be added.\",\n \"The weighting agent can be any of the high density materials conventionally employed (e.g., barites, whiting, or calcined clay) to achieve a desired density (e.g., about 1.05 g/ml to about 2 g/ml or about 65 lbs/ft3 to about 125 lbs/ft3).\",\n \"Other solid additives can include organoclays, e.g., organophilic clays, that can help suspend drill cuttings.\",\n \"One particular commercial organophilic clay that can be used can be or include the organophilic clay sold under the name VG-Plus sold by M-I Swaco, LLC.\",\n \"Fluid loss additives, which can serve to increase viscosity and/or reduce the escape of the fluid into permeable formations traversed by the well bore, can be incorporated into the invert emulsion.\",\n \"The amount added should not increase the viscosity of the composition to such an extent that efficient pumping of the drilling fluid is compromised.\",\n \"The fluid loss component additive can be or include a hydratable clay or clay-like material, although asphalt, carbon black, or any conventional additive can be used.\",\n \"High quality clays such as bentonite, montmorillonite, and kaolinite are often employed.\",\n \"Other conventional additives, including filter loss agents, other viscosifiers, wetting agents, stabilizers, gel strength, and/or rheological control agents can be incorporated into the invert emulsion drilling fluid.\",\n \"EXAMPLES In order to provide a better understanding of the foregoing discussion, the following non-limiting examples are offered.\",\n \"Although the examples can be directed to specific embodiments, they are not to be viewed as limiting the invention in any specific respect.\",\n \"Synthesis of Emulsifier C1 A condenser and a Barrett trap were attached to a reaction vessel.\",\n \"To the reaction vessel was added 1,656.2 g of XTOL® 100 (available from Georgia-Pacific Chemicals LLC).\",\n \"The XTOL® 100 was heated to 90° C. under nitrogen for 1 hour.\",\n \"To the XTOL® 100 was slowly added 303.4 g of diethylenetriamine, 7.3 g of triethylenetetramine, and 7.3 g tetraethylenepentamine to form a reaction mixture.\",\n \"The reaction mixture was heated to 160° C. for 4 hours.\",\n \"From the reaction mixture 97 g of distillate was collected in the Barrett trap.\",\n \"The reaction mixture was cooled to 66° C. and 225.9 g maleic anhydride was added in small quantity additions.\",\n \"The temperature of the reaction mixture increased to approximately 85° C. over 105 minutes.\",\n \"The triamide reaction product was obtained in a 93% yield with a final acid value of 61.4 mg KOH/gram of sample, and a total amine value of 20.5 mg KOH/gram of sample.\",\n \"The triamide was a waxy, brown solid, which had a Brookfield viscosity of 75 cP at 140° C. The triamide was then mixed with a modified tall oil product in a ratio of 67 wt % modified tall oil product to 33 wt % of the triamide.\",\n \"The modified tall oil product was a reaction product of tall oil and maleic anhydride, which yielded a 12 wt % maleation.\",\n \"The tall oil for the maleation was 69 wt % of tall oil fatty acids and 31 wt % of rosin acids, based on the combined weight of the tall oil fatty acids and the rosin acids.\",\n \"The mixture of the triamide and modified tall oil product had an acid value of 198.6 mg KOH/gram of sample and a total amine value of 3.5 mg KOH/gram of sample.\",\n \"The mixture of the triamide and modified tall oil product was then heated to 90° C. and neutralized by slowly adding to a pre-mixed solution of 250 grams of tap water and 70.8 grams of 50% sodium hydroxide solution.\",\n \"The final acid number of the neutralized product was adjusted to 0.5 mg KOH/gram of solution with a solids content of 48.9% and a final pH of 11.3.The mixture was adjusted to 21.3 wt % solids, and spray dried on a Niro laboratory spray dryer.\",\n \"Synthesis of Emulsifier Ex.\",\n \"1 A condenser and a Barrett trap were attached to a reaction vessel.\",\n \"To the reaction vessel was added 839 g of XTOL® 100 (available from Georgia-Pacific Chemicals LLC).\",\n \"The XTOL® 100 was heated to 90° C. under nitrogen for 1 hour.\",\n \"To the XTOL® 100 was slowly added 153.7 g of diethylenetriamine, 3.7 g of triethylenetetramine, and 3.7 g tetraethylenepentamine to form a reaction mixture.\",\n \"The reaction mixture was heated to 160° C. for 3 hours.\",\n \"From the reaction mixture, 47.1 g of distillate was collected in the Barrett trap.\",\n \"The reaction mixture was cooled to 85° C. and decanted.\",\n \"The isolated amidoamine had a final acid value of 9.9 mg KOH/ gram of sample and a total amine value of 106.4 mg KOH/gram of sample.\",\n \"To 188.4 g of the isolated reaction mixture was added 22 g of succinic anhydride.\",\n \"The reaction mixture was heated at 120° C. for 2 hours.\",\n \"The triamide reaction product was a waxy, brown solid obtained in a 93% yield with a final acid value of 51.3 mg KOH/gram of sample and a total amine value of 37.6 mg KOH/gram of sample.\",\n \"The triamide was then mixed with a modified tall oil product in a ratio of 67 wt % modified tall oil product to 33 wt % of the triamide.\",\n \"The modified tall oil product was a reaction product of tall oil and maleic anhydride, which yielded a 12 wt % maleation.\",\n \"The tall oil for the maleation was 69 wt % of tall oil fatty acids and 31 wt % of rosin acids, based on the combined weight of the tall oil fatty acids and the rosin acids.\",\n \"The mixture of the triamide and modified tall oil product had an acid value of 168.8 mg KOH/gram of sample and a total amine value of 9.9 mg KOH/gram of sample.\",\n \"The mixture of the triamide and modified tall oil product was then heated to 90° C. and neutralized by slowly adding to a pre-mixed solution of 150 grams of tap water and 36.1 grams of 50% sodium hydroxide solution.\",\n \"The final acid number of the neutralized product was adjusted to 0.6 mg KOH/gram of solution and a solids content of 50 wt %.\",\n \"This solution was then spray dried on a Niro laboratory spray dryer.\",\n \"Drilling Fluids for Emulsifiers C1 and Ex.\",\n \"1 Comparative and inventive drilling fluids were made.\",\n \"The drilling fluids were prepared by combining the ingredients in a Hamilton Beach mixer and then shearing the composition for 5 minutes at 6,000 rpm in a Silverson shear mixer.\",\n \"The compositions for the comparative drilling fluid and the inventive drilling fluid are shown in Table 1.TABLE 1 Drilling Fluids Comparative Drilling Inventive Drilling Mix time after Fluid Fluid addition #2 Diesel 180.5 g 180.5 g VG-Plus 6 g 6 g 10 minutes Lime 2 g 2 g 5 minutes Emulsifier C1 5 g 0 g Emulsifier Ex.\",\n \"1 0 g 5 g 25 wt % CaCl2 (aq) 71.5 g 71.5 g 10 minutes Barite 281 g 281 g 5 minutes Both the comparative drilling fluid and the inventive drilling fluid were of the same compositions except for the triamide used.\",\n \"The comparative drilling fluid used comparative emulsifier (C1).\",\n \"The comparative emulsifier was a spray dried mixture of tall oil and a triamide of Formula (I) except R4 was a C2-alkylene diyl group (e.g., ethylene group).\",\n \"The inventive drilling fluid used emulsifier (Ex.\",\n \"1), which was a spray dried mixture of tall oil and triamide of Formula (I) where R4 was a C2-alkenylene diyl group (e.g., ethylene diyl group).\",\n \"The before hot roll (BHR) rheology, plastic viscosity, yield point, electrical stability, and gel strengths for the comparative and inventive drilling fluids were measured.\",\n \"Then, the drilling fluids were hot rolled for 16 hours at 150° F. and the after hot roll (AHR) rheology, plastic viscosity (PV), yield point (YP), electrical stability (ES), ten second gel strength (10″), and ten minute gel strength (10′) were measured.\",\n \"The inventive drilling fluid was tested twice.\",\n \"Table 2 shows the results for the rheology tests.\",\n \"TABLE 2 Rheology Properties Comparative Inventive Inventive Drilling Drilling Fluid Drilling Fluid Fluid (Test 1) (Test 2) AHR AHR AHR AHR AHR AHR Rheology BHR 40° F. 150° F. BHR 40° F. 150° F. BHR 40° F. 150° F. 600 rpm 50 170 57 54 158 53 50 158 52 300 rpm 30 102 35 33 93 31 29 92 28 200 rpm 23 79 27 25 70 23 21 68 21 100 rpm 16 52 20 18 45 15 15 43 14 6 rpm 8 21 10 9 15 7 7 18 6 3 rpm 7 19 10 8 13 6 6 12 6 PV 20 68 22 21 65 22 21 66 24 YP 10 34 13 12 28 9 8 26 4 10″ Gel 9 22 11 10 16 8 7 16 7 10′ Gel 13 33 15 16 26 15 10 21 10 All testing on oil-based drilling fluids was conducted according to the API Recommended Practice Standard 13B-2, Third Edition, February 1998.The rheology data given in Table 2 indicates that the inventive drilling fluids (Tests 1 and 2) show a lower rheological profile at lower rpms (e.g., about 3 rpm to about 6 rpm), lower yield points, and lower gel strengths for the inventive fluids as compared to the comparative drilling fluid.\",\n \"The electric stability test is an indication of the quality of the invert emulsion.\",\n \"Table 3 shows the results of the electrical stability test.\",\n \"TABLE 3 Electrical stability Inventive Inventive Comparative Drilling Drilling Drilling Fluid Fluid Fluid (Test 1) (Test 2) AHR AHR AHR BHR 150° F. BHR 150° F. BHR 150° F. ES (Volts at 752 1141 837 1018 701 894 150° F.) The electrical stability of the inventive fluids showed similar values before hot roll (BHR) and equivalent or slightly lower electrical stability after hot roll (AHR).\",\n \"The high temperature/high pressure fluid loss tests were conducted with a 500 psi differential pressure between the top and the bottom of the HTHP cell.\",\n \"The HTHP fluid loss test was performed after hot rolling at a 150° F. The HTHP fluid loss testing was performed at 250° F. As shown in Table 4, the results of the high temperature/high pressure fluid loss testing indicate that the inventive fluids (Tests 1 and 2) have lower fluid loss versus the comparative fluid.\",\n \"These results indicate that the inventive fluids have a lower loss of fluid to the formation, which is highly desirable especially when drilling in sensitive formations.\",\n \"TABLE 4 High Temperature/High Pressure and Water Loss Comparative Inventive Drilling Inventive Drilling Drilling Fluid Fluid (Test 1) Fluid (Test 2) AHR 150° F. AHR 150° F. AHR 150° F. HT/HP at 8.2 6.0 6.0 250° F. (mL) Water Loss 0 0 0 (mL) Comparative and inventive drilling fluids were made under contaminated conditions using API Standard Evaluation Clay (API Clay) (See Table 5).\",\n \"TABLE 5 Drilling Fluids With API Clay Comparative Drilling Inventive Drilling Mix time after Fluid Fluid addition #2 Diesel 180.5 g 180.5 g VG-Plus 6 g 6 g 10 minutes Lime 2 g 2 g 5 minutes Emulsifier C1 5 g 0 g Emulsifier Ex.\",\n \"1 0 g 5 g 25 wt % CaCl2 (aq) 71.5 g 71.5 g 10 minutes Barite 281 g 281 g 5 minutes API Clay 20 g 20 g 5 minutes The results of the contamination studies using the API Standard Evaluation Clay are shown in Table 6.The inventive drilling fluid is very effective at maintaining low end (e.g., about 3 rpm to about 6 rpm) rheology while maintaining yield point and gel strengths in the presence of API grade bentonite clay.\",\n \"TABLE 6 Rheology Properties With API Clay Comparative Inventive Inventive Drilling Drilling Fluid Drilling Fluid Fluid (Test 1) (Test 2) AHR AHR AHR AHR AHR AHR Rheology BHR 40° F. 150° F. BHR 40° F. 150° F. BHR 40° F. 150° F. 600 rpm 58 189 59 65 195 64 57 195 62 300 rpm 36 110 34 42 113 38 35 114 36 200 rpm 30 83 28 35 85 30 29 86 28 100 rpm 22 53 20 26 54 21 22 55 19 6 rpm 12 18 10 15 18 10 12 18 9 3 rpm 12 15 9 13 15 9 11 15 8 PV 22 79 25 23 82 26 22 81 26 YP 14 31 9 19 31 12 13 33 10 10″ Gel 14 18 10 15 18 12 13 18 10 10′ Gel 18 25 15 21 25 17 15 27 16 Table 7 shows the electric stability tests for the comparative and inventive drilling fluids in the presence of clay.\",\n \"TABLE 7 Electrical Stability With API Clay Inventive Inventive Comparative Drilling Drilling Drilling Fluid Fluid Fluid (Test 1) (Test 2) AHR AHR AHR BHR 150° F. BHR 150° F. BHR 150° F. ES (Volts at 375 588 448 608 572 735 150° F.) The electrical stability of the inventive fluids showed similar values before hot roll (BHR) and slightly higher electrical stability values after hot roll (AHR).\",\n \"Table 8 shows the results of the high temperature/high pressure fluid loss testing indicate that the inventive fluids (Tests 1 and 2) have lower fluid loss versus the comparative fluid in the presence of API grade bentonite clay.\",\n \"TABLE 8 High Temperature/High Pressure and Water Loss With API Clay Comparative Inventive Drilling Inventive Drilling Drilling Fluid Fluid (Test 1) Fluid (Test 2) AHR 150° F. AHR 150° F. AHR 150° F. HT/HP at 12.0 7.6 6.6 250° F. Water Loss 0 0 0 Synthesis of Emulsifier C2 A condenser and a Barrett trap were attached to a reaction vessel.\",\n \"To the reaction vessel was added 662.1 g of coconut oil.\",\n \"The coconut oil was heated to 90° C. under nitrogen for 1 hour.\",\n \"To the coconut oil was slowly added 203.6 g of diethylenetriamine to form a reaction mixture.\",\n \"The temperature of the reaction mixture was increased to approximately 120° C. over approximately 30 minutes.\",\n \"The reaction mixture was heated to 130° C. for 4 hours and to 160° C. for an additional 4 hours.\",\n \"The reaction mixture was the cooled to 85° C. and decanted.\",\n \"The isolated amidoamine had a final acid value of 9.9 mg KOH/ gram of sample and a total amine value of 106.4 mg KOH/gram of sample.\",\n \"To 326.1 g of the isolated reaction mixture was added 44 g of maleic anhydride slowly, and the reaction mixture was heated to 70° C. The temperature was increased to approximately 80° C. over approximately 30 minutes.\",\n \"The triamide reaction product was a waxy, brown solid obtained in a 93% yield, and having a final acid value of 70.6 mg KOH/gram of sample and a total amine value of 18.8 mg KOH/gram of sample.\",\n \"The triamide was then mixed with a modified tall oil product in a ratio of 67 wt % modified tall oil product to 33 wt % of the triamide.\",\n \"The modified tall oil product was a reaction product of tall oil and maleic anhydride, which yielded a 12 wt % maleation.\",\n \"The tall oil for the maleation was 69 wt % of tall oil fatty acids and 31 wt % of rosin acids, based on the combined weight of the tall oil fatty acids and the rosin acids.\",\n \"The mixture of the triamide and modified tall oil product had an acid value of 202.1 mg KOH/gram of sample and a total amine value of 5.1 mg KOH/gram of sample.\",\n \"The mixture of the triamide and modified tall oil product was then heated to 90° C. and neutralized by slowly adding a solution of 200 grams of tap water and 57.7 grams of 50% sodium hydroxide solution.\",\n \"The final acid number of the neutralized product was adjusted to 0.8 mg KOH/gram of solution and a solids content of 49.1 wt %.\",\n \"This solution was then spray dried on a Niro laboratory spray dryer.\",\n \"Synthesis of Emulsifier Ex.\",\n \"2 The amidoamine product of the inventive emulsifier was made identically as describe above for emulsifier C2.To 348.1 g of the isolated reaction mixture was added 54.7 g of succinic anhydride.\",\n \"The reaction mixture was heated to 130° C. for 2 hours then to 140° C. for 2 hours.\",\n \"The triamide reaction product was a waxy, brown solid obtained in a 93% yield with a final acid value of 42.8 mg KOH/gram of sample and a total amine value of 17.5 mg KOH/gram of sample.\",\n \"The triamide was then mixed with a modified tall oil product in a ratio of 67 wt % modified tall oil product to 33 wt % of the triamide.\",\n \"The modified tall oil product was a reaction product of tall oil and maleic anhydride, which yielded a 12 wt % maleation.\",\n \"The tall oil for the maleation was 69 wt % of tall oil fatty acids and 31 wt % of rosin acids, based on the combined weight of the tall oil fatty acids and the rosin acids.\",\n \"The mixture of the triamide and modified tall oil product was then heated to 90° C. and neutralized by slowly adding a solution of 200 grams of tap water and 57.7 grams of 50% sodium hydroxide solution.\",\n \"The mixture of the triamide and modified tall oil product had an acid value of 188 mg KOH/gram of sample and a total amine value of 5.1 mg KOH/gram of sample.\",\n \"Drilling Fluids for Emulsifiers C2 and Ex.\",\n \"2 Comparative and inventive drilling fluids were made with using the emulsifiers containing coconut oil.\",\n \"The drilling fluids were prepared by combining the ingredients in a Hamilton Beach mixer and then shearing the composition for 5 minutes at 6,000 rpm in a Silverson shear mixer.\",\n \"The compositions for the comparative drilling fluid and the inventive drilling fluid are shown in Table 9.TABLE 9 Drilling Fluids Comparative Drilling Inventive Drilling Mix time after Fluid Fluid addition #2 Diesel 180.5 g 180.5 g VG-Plus 6 g 6 g 10 minutes Lime 2 g 2 g 5 minutes Emulsifier C2 5 g 0 g Emulsifier Ex.\",\n \"2 0 g 5 g 25 wt % CaCl2 (aq) 71.5 g 71.5 g 10 minutes Barite 281 g 281 g 5 minutes Both the comparative drilling fluid and the inventive drilling fluid were of the same compositions except for the triamide used in the emulsifier.\",\n \"The comparative drilling fluid used comparative emulsifier (C2).\",\n \"The comparative emulsifier was a mixture of tall oil and a triamide of Formula (I) except R4 was a C2-alkylene diyl group (e.g., ethylene group).\",\n \"The inventive drilling fluid used emulsifier (Ex.\",\n \"2), which was a spray dried mixture of tall oil and triamide of Formula (I) where R4 was a C2-alkenylene diyl group (e.g., ethylene diyl group).\",\n \"The before hot roll rheology, plastic viscosity, yield point, electrical stability, and gel strengths for the comparative and inventive drilling fluids were measured.\",\n \"The drilling fluids were then hot rolled for 16 hours at 40° F. and 150° F. and the after hot roll rheology, plastic viscosity, yield point, electrical stability, ten second minute gel strengths, and ten minute gel strength were measured.\",\n \"Table 10 shows the results for the rheology tests.\",\n \"TABLE 10 Rheology Properties Comparative Inventive Drilling Fluid Drilling Fluid AHR AHR AHR AHR Rheology BHR 40° F. 150° F. BHR 40° F. 150° F. 600 rpm 65 177 67 60 164 58 300 rpm 45 110 44 40 96 35 200 rpm 37 84 37 32 72 28 100 rpm 29 56 28 24 46 20 6 rpm 18 20 17 13 15 10 3 rpm 7 18 17 12 13 9 PV 20 67 23 20 68 23 YP 25 43 21 20 28 12 10″ Gel 17 21 16 12 15 12 10′ Gel 20 29 21 14 19 14 Table 11 shows the results of the electrical stability test.\",\n \"TABLE 11 Electrical Stability Comparative Drilling Fluid Inventive Drilling Fluid BHR AHR 150° F. BHR AHR 150° F. ES (Volts at 857 1160 800 1051 150° F.) Table 12 shows the results for the high temperature/high pressure water loss test for the comparative drilling fluid using C2 and the inventive drilling fluid using Ex 2.TABLE 12 High Temperature/High Pressure and Water Loss Comparative Drilling Fluid Inventive Drilling Fluid AHR 250° F. C AHR 150° F. HT/HP at 9.4 8.6 250° F. Water 0 0 Loss Comparative and inventive drilling fluids were made again with the addition of API grade bentonite clay.\",\n \"The compositions are shown in Table 13.TABLE 13 Drilling Fluids With API Clay Comparative Inventive Mix time Drilling Fluid Drilling Fluid after addition #2 Diesel 180.5 g 180.5 g VG-Plus 6 g 6 g 10 minutes Lime 2 g 2 g 5 minutes Emulsifier C2 5 g 0 g Emulsifier Ex.\",\n \"2 0 g 5 g 25 wt % CaCl2 (aq) 71.5 g 71.5 g 10 minutes Barite 281 g 281 g 5 minutes API Clay 20 g 20 g 5 minutes The before hot roll rheology, plastic viscosity, yield point, electrical stability, and gel strengths for the comparative and inventive drilling fluids were measured.\",\n \"The drilling fluids were then hot rolled for 16 hours at 40° F. and 150° F. and the after hot roll rheology, plastic viscosity, yield point, electrical stability, ten second gel strengths, and ten minute gel strength were measured.\",\n \"The rheology properties of the comparative and inventive drilling fluids are shown in Table 14.TABLE 14 Rheology Properties With the Addition of API Clay Comparative Inventive Drilling Fluid Drilling Fluid AHR AHR AHR AHR Rheology BHR 40° F. 150° F. BHR 40° F. 150° F. 600 rpm 73 232 67 63 216 69 300 rpm 51 138 41 41 128 42 200 rpm 42 103 34 32 97 33 100 rpm 32 66 25 23 62 24 6 rpm 20 23 13 13 21 12 3 rpm 19 20 12 1 18 12 PV 22 94 26 22 88 27 YP 29 44 15 19 40 15 10″ Gel 18 23 15 12 19 12 10′ Gel 22 29 17 15 23 16 Table 15 shows the results of the electrical stability test for the comparative drilling fluid using C2 and the inventive drilling fluid using Ex 2.TABLE 15 Electrical Stability With API Clay Comparative Inventive Drilling Fluid Drilling Fluid BHR AHR 150° F. BHR AHR 150° F. ES (Volts at 150° F.) 500 783 508 665 Table 16 shows the results for the high temperature/high pressure water loss test for the inventive drilling fluid using C2 and the inventive drilling fluid using Ex 2.TABLE 16 High Temperature/High Pressure and Water Loss With API Clay Comparative Inventive Drilling Fluid Drilling Fluid AHR 150° F. AHR 150° F. HT/HP at 250° F. 11.4 11.6 Water Loss 0 0 Synthesis of Emulsifier C3 A condenser and a Barrett trap were attached to a reaction vessel.\",\n \"To the reaction vessel were added 446.5 g of soybean oil and 453.5 g of Tall Oil Fatty Acid.\",\n \"The mixture was heated to 90° C. under nitrogen.\",\n \"To the soybean oil and Tall Oil Fatty Acid mixture was slowly added 163.7 g of diethylenetriamine to make a reaction mixture.\",\n \"The temperature of the reaction mixture was increased to approximately 120° C. over approximately 30 minutes.\",\n \"The reaction mixture was then heated to 130° C. for 2 hours and 160° C. for an additional 4 hours.\",\n \"The reaction mixture was the cooled to 85° C., and decanted.\",\n \"The isolated amidoamine had a final acid value of 11.8 mg KOH/gram of sample and a total amine value of 94.3 mg KOH/gram of sample.\",\n \"To 1,053.6 g of the isolated amidoamine, which was heated to 70° C., was slowly added 188.3 g of maleic anhydride.\",\n \"The reaction mixture increased in temperature to approximately 80° C. over approximately a 30 minute period.\",\n \"The triamide reaction product was a waxy, brown solid obtained in a 93% yield with a final acid value of 64 mg KOH/gram of sample and a total amine value of 21.1 mg KOH/gram of sample.\",\n \"The triamide reaction product was mixed with a modified tall oil product to produce a mixture that had an acid value of 197.3 mg KOH/gram of sample and a total amine value of 6.2 mg KOH/gram of sample.\",\n \"The mixture of the triamide and modified tall oil product (240 g) was heated to 50° C. and neutralized by slowly adding to a solution of 240 grams of tap water and 67.5 grams of 50% sodium hydroxide solution.\",\n \"The final acid number of the neutralized product was adjusted to 0.6 mg KOH/gram of solution and a solids content of 48.8 wt %.\",\n \"This solution was then spray dried on a Niro laboratory spray dryer.\",\n \"Synthesis of Emulsifier Ex.\",\n \"3 A condenser and a Barrett trap were attached to a reaction vessel.\",\n \"To the reaction vessel were added 429.4 g of soybean oil and 419.3 g of Tall Oil Fatty Acid.\",\n \"The mixture was heated to 90° C. under nitrogen.\",\n \"To the soybean oil and Tall Oil Fatty Acid blend was slowly added 151.3 g of diethylenetriamine to make a reaction mixture.\",\n \"The temperature of the reaction mixture increased to approximately 120° C. over approximately 30 minutes.\",\n \"The reaction mixture was then heated to 130° C. for 2 hours and to 160° C. for an additional 4 hours.\",\n \"The reaction mixture was cooled to 85° C. and then decanted.\",\n \"The isolated amidoamine had a final acid value of 11.6 mg KOH/ gram of sample and a total amine value of 93.1 mg KOH/gram of sample.\",\n \"To 298.1 g of the isolated reaction mixture heated to 130° C. was added 33.3 g of succinic anhydride.\",\n \"The reaction mixture increased in temperature to approximately 140° C. over approximately a 30 minute period.\",\n \"The triamide reaction product was a waxy, brown solid obtained in a 93% yield with a final acid value of 38.5 mg KOH/gram of sample and a total amine value of 29.5 mg KOH/gram of sample.\",\n \"The triamide was then blended with modified tall oil product in a ratio of 65 wt % modified tall oil product to 35 wt % of carboxyl terminated amidoamine made from tall oil fatty acids.\",\n \"The resulting mixture had an acid value of 184.8 mg KOH/gram of sample and a total amine value of 8.3 mg KOH/gram of sample.\",\n \"The mixture of the triamide and modified tall oil product (200 g) was then heated to 90° C. and neutralized by slowly adding a solution of 200 grams of tap water and 52.7 grams of 50% sodium hydroxide solution.\",\n \"The final acid number of the neutralized product was adjusted to 0.2 mg KOH/gram of solution and a solids content of 48.5 wt %.\",\n \"This solution was then spray dried on a Niro laboratory spray dryer.\",\n \"Drilling Fluids for Emulsifiers C3 and Ex.\",\n \"3 The drilling fluids were prepared by combining the ingredients in a Hamilton Beach mixer and then shearing the composition for 5 minutes at 6,000 rpm in a Silverson shear mixer.\",\n \"The compositions for the comparative drilling fluid and the inventive drilling fluid are shown in Table 17.TABLE 17 Drilling Fluids Comparative Inventive Mix time Drilling Fluid Drilling Fluid after addition #2 Diesel 180.5 g 180.5 g VG-Plus 6 g 6 g 10 minutes Lime 2 g 2 g 5 minutes Emulsifier C3 5 g 0 g Emulsifier Ex.\",\n \"3 0 g 5 g 25 wt % CaCl2 (aq) 71.5 g 71.5 g 10 minutes Barite 281 g 281 g 5 minutes Both the comparative drilling fluid and the inventive drilling fluid were of the same compositions except for the triamide used.\",\n \"The comparative drilling fluid used comparative emulsifier (C3).\",\n \"The comparative emulsifier was a mixture of tall oil and a triamide of Formula (I) except R4 was a C2-alkylene diyl group (e.g., ethylene group).\",\n \"The inventive drilling fluid used emulsifier (Ex.\",\n \"3), which was a spray dried mixture of tall oil and triamide of Formula (I) where R4 was a C2-alkenylene diyl group (e.g., ethylene diyl group).\",\n \"The before hot roll rheology, plastic viscosity, yield point, electrical stability, and gel strengths for the comparative and inventive drilling fluids were measured.\",\n \"Then, the drilling fluids were hot rolled for 16 hours at 40° F. and 150° F. and the after hot roll rheology, plastic viscosity, yield point, electrical stability, ten second gel strengths, and ten minute gel strength were measured.\",\n \"Table 18 shows the results for the rheology tests.\",\n \"TABLE 18 Rheology Properties Comparative Inventive Drilling Fluid Drilling Fluid AHR AHR AHR AHR Rheology BHR 40° F. 150° F. BHR 40° F. 150° F. 600 rpm 52 197 66 53 195 62 300 rpm 32 119 39 32 115 35 200 rpm 24 90 32 24 87 30 100 rpm 18 58 24 18 55 21 6 rpm 10 19 13 10 18 12 3 rpm 9 17 13 9 15 1 PV 20 78 27 21 80 27 YP 12 41 12 11 35 8 10″ Gel 10 18 14 11 17 13 10′ Gel 11 27 16 12 22 16 The electric stability Table 19 shows the results of the electrical stability test for the comparative drilling fluid using C3 and the inventive drilling fluid using Ex 3.TABLE 19 Electrical Stability Comparative Inventive Drilling Fluid Drilling Fluid BHR AHR 150° F. BHR AHR 150° F. ES (Volts at 150° F.) 833 1151 824 1145 Table 20 shows the results for the high temperature/high pressure water loss test for the comparative drilling fluid using C3 and the inventive drilling fluid using Ex 3.TABLE 20 High Temperature/High Pressure and Water Loss Comparative Inventive Drilling Fluid Drilling Fluid AHR 150° F. AHR 150° F. HT/HP at 250° F. 10.2 8.2 Water Loss 0 0 Comparative and inventive drilling fluids were made again with the addition of API grade bentonite clay.\",\n \"The compositions are shown in Table 21.TABLE 21 Drilling Fluids With API Clay Comparative Inventive Mix time Drilling Fluid Drilling Fluid after addition #2 Diesel 180.5 g 180.5 g VG-Plus 6 g 6 g 10 minutes Lime 2 g 2 g 5 minutes Emulsifier C3 5 g 0 g Emulsifier Ex.\",\n \"3 0 g 5 g 25 wt % CaCl2 (aq) 71.5 g 71.5 g 10 minutes Barite 281 g 281 g 5 minutes API Clay 20 g 20 g 5 minutes The before hot roll rheology, plastic viscosity, yield point, electrical stability, and gel strengths for the comparative and inventive drilling fluids were measured.\",\n \"The drilling fluids were then hot rolled for 16 hours at 40° F. and 150° F., and the after hot roll rheology, plastic viscosity, yield point, electrical stability, ten second gel strengths, and ten minute gel strength were measured.\",\n \"Table 22 shows the results for the rheology tests.\",\n \"TABLE 22 Rheology Properties with the addition of API Clay Comparative Inventive Drilling Fluid Drilling Fluid AHR AHR AHR AHR Rheology BHR 40° F. 150° F. BHR 40° F. 150° F. 600 rpm 61 221 66 63 242 73 300 rpm 38 130 39 39 143 43 200 rpm 31 96 32 31 107 35 100 rpm 23 60 24 23 68 25 6 rpm 13 20 13 12 21 13 3 rpm 12 18 12 11 18 12 PV 23 91 27 24 99 30 YP 15 39 12 15 44 13 10″ Gel 13 20 14 12 19 14 10′ Gel 17 27 18 15 26 18 Table 23 shows the results of the electrical stability test for the comparative drilling fluid using C3 and the inventive drilling fluid using Ex 3.TABLE 23 Electrical stability Comparative Inventive Drilling Fluid Drilling Fluid BHR AHR 150° F. BHR AHR 150° F. ES (Volts at 150° F.) 464 683 549 870 Table 24 shows the results for the high temperature/high pressure water loss test for the comparative drilling fluid using C3 and the inventive drilling fluid using Ex 3.TABLE 24 High Temperature/High Pressure and Water Loss Comparative Inventive Drilling Fluid Drilling Fluid AHR 150° F. AHR 150° F. HT/HP at 250° F. 10.8 10.8 Water Loss 0 0 Synthesis of Emulsifier C4 A condenser and a Barrett trap were attached to a reaction vessel.\",\n \"To the reaction vessel were added 502.2 g of Palm Olein and 512.3 g of Tall Oil Fatty Acid.\",\n \"The mixture was heated to 90° C. under nitrogen.\",\n \"To the soybean oil and Tall Oil Fatty Acid mixture was slowly added 185.5 g of diethylenetriamine.\",\n \"The temperature of the reaction mixture increased to approximately 120° C. over approximately 30 minutes.\",\n \"The reaction mixture was then heated to 130° C. for 2 hours and to 160° C. for an additional 4 hours.\",\n \"The reaction mixture was cooled to 85° C. and decanted.\",\n \"The isolated amidoamine had a final acid value of 11.7 mg KOH/gram of sample and a total amine value of 117.5 mg KOH/gram of sample.\",\n \"To 350 g of the isolated reaction mixture, which was heated to 70° C., was added 41.7 g of maleic anhydride.\",\n \"The reaction mixture increased in temperature to approximately 90° C. over 30 minutes.\",\n \"The triamide reaction product was a waxy, brown solid obtained in a 93% yield with a final acid value of 50 mg KOH/gram of sample and a total amine value of 22.7 mg KOH/gram of sample.\",\n \"The triamide was then mixed with a modified tall oil product in a ratio of 65 wt % modified tall oil product to 35 wt % of the carboxyl terminated amidoamine.\",\n \"The mixture of the triamide and the modified tall oil product had an acid value of 197.2 mg KOH/gram of sample and a total amine value of 6.7 mg KOH/gram of sample.\",\n \"The mixture of the triamide and the modified tall oil product (200 g) of the mixture was heated to 50° C. and neutralized by slowly adding a solution of 200 grams of tap water and 56.3 grams of 50% sodium hydroxide solution.\",\n \"The final acid number of the neutralized product was adjusted to 0.3 mg KOH/gram of solution and a solids content of 48.9 wt %.\",\n \"This solution was then spray dried on a Niro laboratory spray dryer.\",\n \"Synthesis of Emulsifier Ex.\",\n \"4 A condenser and a Barrett trap were attached to a reaction vessel.\",\n \"To the reaction vessel were added 502.2 g of Palm Olein and 512.3 g of Tall Oil Fatty Acid to form a mixture.\",\n \"The mixture was heated to 90° C. under nitrogen.\",\n \"To the soybean oil and Tall Oil Fatty Acid mixture was slowly added 185.5 g of diethylenetriamine to form a reaction mixture.\",\n \"The temperature of the reaction mixture increased to approximately 120° C. for 30 minutes.\",\n \"The reaction mixture was then heated to 130° C. for 2 hours and then to 160° C. for approximately 4 hours.\",\n \"The reaction mixture was cooled to 85° C. and decanted.\",\n \"The isolated amidoamine had a final acid value of 11.7 mg KOH/gram of sample and a total amine value of 117.5 mg KOH/gram of sample.\",\n \"To 350 g of the isolated reaction mixture, which was heated to 125° C., was slowly added 42.6 g of succinic anhydride.\",\n \"The reaction mixture increased in temperature to approximately 137° C. over approximately a 30 minute period.\",\n \"The triamide reaction product was a waxy, brown solid obtained in a 93% yield with a final acid value of 52.4 mg KOH/gram of sample and a total amine value of 30 mg KOH/gram of sample.\",\n \"The triamide was then mixed with a modified tall oil product in a ratio of 65 wt % modified tall oil product to 35 wt % of carboxyl terminated amidoamine.\",\n \"The mixture of the triamide and the modified tall oil product had an acid value of 180 mg KOH/gram of sample and a total amine value of 10 mg KOH/gram of sample.\",\n \"The mixture of the triamide and the modified tall oil product (200 g) of the mixture was heated to 50° C. and neutralized by slowly adding a solution of 200 grams of tap water and 51.4 grams of 50% sodium hydroxide solution.\",\n \"The final acid number of the neutralized product was adjusted to 0.2 mg KOH/gram of solution and a solids content of 49.1%.\",\n \"This solution was then spray dried on a Niro laboratory spray dryer.\",\n \"The drilling fluids were prepared by combining the ingredients in a Hamilton Beach mixer and then shearing the composition for 5 minutes at 6,000 rpm in a Silverson shear mixer.\",\n \"The compositions for the comparative drilling fluid and the inventive drilling fluid are shown in Table 25.TABLE 25 Drilling Fluids Comparative Inventive Mix time Drilling Fluid Drilling Fluid after addition #2 Diesel 180.5 g 180.5 g VG-Plus 6 g 6 g 10 minutes Lime 2 g 2 g 5 minutes Emulsifier C4 5 g 0 g Emulsifier Ex.\",\n \"4 0 g 5 g 25 wt % CaCl2 (aq) 71.5 g 71.5 g 10 minutes Barite 281 g 281 g 5 minutes Both the comparative drilling fluid and the inventive drilling fluid were of the same compositions except for the triamide used.\",\n \"The comparative drilling fluid used comparative emulsifier (C4).\",\n \"The comparative emulsifier was a mixture of tall oil and a triamide of Formula (I) except R4 was a C2-alkylene diyl group (e.g., ethylene group).\",\n \"The inventive drilling fluid used emulsifier (Ex.\",\n \"4), which was a spray dried mixture of tall oil and triamide of Formula (I) where R4 was a C2-alkenylene diyl group (e.g., ethylene diyl group).\",\n \"The before hot roll rheology, plastic viscosity, yield point, electrical stability, and gel strengths for the comparative and inventive drilling fluids were measured.\",\n \"Then, the drilling fluids were hot rolled for 16 hours at 40° F. and 150° F. and the after hot roll rheology, plastic viscosity, yield point, electrical stability, ten second gel strengths, and ten minute gel strength were measured.\",\n \"Table 26 shows the results for the rheology tests.\",\n \"TABLE 26 Rheology Properties Comparative Inventive Drilling Fluid Drilling Fluid AHR AHR AHR AHR Rheology BHR 40° F. 150° F. BHR 40° F. 150° F. 600 rpm 54 220 70 52 188 64 300 rpm 34 136 45 31 113 39 200 rpm 25 105 37 24 86 31 100 rpm 18 70 28 18 56 22 6 rpm 10 25 17 9 19 13 3 rpm 9 23 16 9 17 12 PV 20 84 25 21 75 25 YP 14 52 20 10 38 14 10″ Gel 7 24 16 9 19 14 10′ Gel 10 34 19 10 24 16 Table 27 shows the results of the electrical stability test for the comparative drilling fluid using C4 and the inventive drilling fluid using Ex 4.TABLE 27 Electrical stability Comparative Inventive Drilling Fluid Drilling Fluid BHR AHR 150° F. BHR AHR 150° F. ES (Volts at 150° F.) 770 1203 764 1170 Table 28 shows the results for the high temperature/high pressure water loss test for the comparative drilling fluid using C4 and the inventive drilling fluid using Ex 4.TABLE 28 High Temperature/High Pressure and Water Loss Comparative Inventive Drilling Fluid Drilling Fluid AHR 150° F. AHR 150° F. HT/HP at 250° F. 12.2 11.0 Water Loss 0.4 0.4 Comparative and inventive drilling fluids were made again with the addition of API grade bentonite clay.\",\n \"The compositions are shown in Table 29.TABLE 29 Drilling Fluids With API Clay Comparative Inventive Mix time Drilling Fluid Drilling Fluid after addition #2 Diesel 180.5 g 180.5 g VG-Plus 6 g 6 g 10 minutes Lime 2 g 2 g 5 minutes Emulsifier C4 5 g 0 g Emulsifier Ex.\",\n \"4 0 g 5 g 25 wt % CaCl2 (aq) 71.5 g 71.5 g 10 minutes Barite 281 g 281 g 5 minutes API Clay 20 g 20 g 5 minutes The before hot roll rheology, plastic viscosity, yield point, electrical stability, and gel strengths for the comparative and inventive drilling fluids were measured.\",\n \"The drilling fluids were then hot rolled for 16 hours at 40° F. and 150° F., and the after hot roll rheology, plastic viscosity, yield point, electrical stability, ten second gel strengths, and ten minute gel strength were measured.\",\n \"Table 30 shows the results for the rheology tests.\",\n \"TABLE 30 Rheology Properties With API Clay Comparative Inventive Drilling Fluid Drilling Fluid AHR AHR AHR AHR Rheology BHR 40° F. 150° F. BHR 40° F. 150° F. 600 rpm 54 249 69 57 217 75 300 rpm 32 147 42 33 132 47 200 rpm 26 110 34 25 102 38 100 rpm 19 70 25 18 69 28 6 rpm 10 25 14 9 26 16 3 rpm 10 21 12 9 23 15 PV 22 102 27 24 85 28 YP 10 45 15 9 47 19 10″ Gel 10 21 14 10 22 17 10′ Gel 13 27 18 11 29 21 Table 31 shows the results of the electrical stability test for the comparative drilling fluid using C4 and the inventive drilling fluid using Ex 4.TABLE 31 Electrical Stability With API Clay Comparative Inventive Drilling Fluid Drilling Fluid BHR AHR 150° F. BHR AHR 150° F. ES (Volts at 150° F.) 391 600 360 551 Table 32 shows the results for the high temperature/high pressure water loss test for the comparative drilling fluid using C4 and the inventive drilling fluid using Ex 4.TABLE 32 High Temperature/High Pressure and Water Loss With API Clay Comparative Inventive Drilling Fluid Drilling Fluid AHR 150° F. AHR 150° F. HT/HP at 250° F. 14.8 14.6 Water Loss 0.2 0.2 Embodiments of the present disclosure further relate to any one or more of the following paragraphs: 1.A method for making an emulsifier, comprising: mixing a tall oil and a triamide, wherein the triamide has the chemical formula: wherein: x, y, and z are integers independently selected from 1 to 10, R1 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl, R2 is H or independently selected for each [(CH2)xNR2(CH2)y] unit, wherein R4 is a C1-C3 alkylene or a C1-C3 alkylene alcohol, and wherein at least one R2 is and R3 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl.\",\n \"2.The method according to paragraph 1, wherein the mixture has a triamide to tall oil weight ratio of about 1:4 to about 2:3.3.The method according to paragraph 1 or 2, wherein R4 is an ethanediyl group (—CH2CH2—).\",\n \"4.The method according to any one of paragraphs 1 to 3, further comprising spray drying the mixture to produce a spray dried emulsifier having an average particle size of about 1 μm to about 75 μm.\",\n \"5.The method according to any one of paragraphs 1 to 4, wherein the emulsifier is at least partially neutralized before spray drying.\",\n \"6.The method according to any one of paragraphs 1 to 5, wherein the mixture is diluted with an aqueous diluent to provide a solids content of about 35 wt % to about 50 wt %, based on the weight of the emulsifier prior to spray drying.\",\n \"7.The method according to any one of paragraphs 1 to 6, wherein the spray dried emulsifier has an average particle size of about 30 μm to about 75 μm.\",\n \"8.The method according to any one of paragraphs 1 to 7, wherein the spray dried emulsifier has a bulk density of about 0.24 g/mL to about 0.56 g/mL.\",\n \"9.The method according to any one of paragraphs 1 to 8, wherein the tall oil comprises crude tall oil, distillate tall oil, tall oil bottoms, or any mixture thereof.\",\n \"10.The method according to any one of paragraphs 1 to 9, wherein the tall oil comprises is a reaction product of at least tall oil and an α, β unsaturated carboxylic acid or an α,β unsaturated acid anhydride.\",\n \"11.The method according to any one of paragraphs 1 to 10, wherein the tall oil is a Diels-Alder product, an ene product, or any mixture thereof.\",\n \"12.The method according to any one of paragraphs 1 to 11, wherein the Diels-Alder product, the ene product, or the mixture thereof is oxidized to provide an ether bond between at least two or more hydrocarbon backbones.\",\n \"13.The method according to any one of paragraphs 1 to 12, wherein the tall oil is dimerized by a carbon-carbon bond between at least two or more hydrocarbon backbones.\",\n \"14.The method according to any one of paragraphs 1 to 13, wherein the tall oil is oxidized to provide an ether bond between at least two or more hydrocarbon backbones.\",\n \"15.The method according to any one of paragraphs 1 to 14, wherein the tall oil comprises a mixture of a first tall oil distillate fraction and a second tall oil distillate fraction comprising about 45 wt % to about 90 wt % of fatty acids and about 10 wt % to about 55 wt % of rosin acids, based on the combined weight of the first tall oil distillate fraction and the second tall oil distillate fraction.\",\n \"16.A method for making an emulsifier, comprising: mixing a triamide and a tall oil, wherein the triamide is prepared by reacting a diamidoamine with a saturated dicarboxylic acid, a saturated acid anhydride, or a mixture thereof; and spray drying the mixture to provide a spray dried emulsifier.\",\n \"17.The method according to paragraph of 16, wherein the mixture has a triamide to tall oil weight ratio of about 1:4 to about 2:3.18.The method according to paragraph 16 or 17, wherein the saturated dicarboxylic acid is succinic acid or the saturated anhydride is succinic anhydride.\",\n \"19.The method according to any one of paragraphs of 16 to 18, wherein the saturated dicarboxylic acid is glutaric acid or the saturated anhydride is glutaric anhydride.\",\n \"20.The method according to any one of paragraphs of 16 to 19, wherein the diamidoamine is a reaction product from one or more fatty acids and one or more polyamines.\",\n \"21.The method according to any one of paragraphs of 16 to 20, wherein the one or more polyamine has the formula H2[(CH2)xNH]yH, wherein x and y are integers independently selected from 1 to 10.22.The method according to any one of paragraphs of 16 to 21, wherein emulsifier is at least partially neutralized before spray drying.\",\n \"23.The method according to any one of paragraphs of 16 to 22, wherein the emulsifier has, or is diluted with an aqueous diluent to provide, a solids content of about 35 wt % to about 50 wt %, based on the weight of the emulsifier prior to spray drying.\",\n \"24.The method according to any one of paragraphs of 16 to 23, wherein the tall oil comprises crude tall oil, distillate tall oil, tall oil bottoms, or any mixture thereof.\",\n \"25.The method according to any one of paragraphs of 16 to 24, wherein the tall oil comprises a mixture of a first tall oil distillate fraction and a second tall oil distillate fraction comprising about 45 wt % to about 90 wt % of fatty acids and about 10 wt % to about 55 wt % of rosin acids, based on the combined weight of the first tall oil distillate fraction and the second tall oil distillate fraction.\",\n \"26.The method according to any one of paragraphs of 16 to 25, wherein the tall oil comprises is a reaction product of at least tall oil and an α,β unsaturated carboxylic acid or an α,β unsaturated acid anhydride.\",\n \"27.The method according to any one of paragraphs of 16 to 26, wherein the tall oil is a Diels-Alder product, an Alder-ene product, or any mixture thereof.\",\n \"28.The method according to any one of paragraphs of 16 to 27, wherein the Diels-Alder product, the ene product, or the mixture thereof is oxidized to provide an ether bond between at least two or more hydrocarbon backbones.\",\n \"29.The method according to any one of paragraphs of 16 to 28, wherein the tall oil is dimerized by a carbon-carbon bond between at least two or more hydrocarbon backbones.\",\n \"30.The method according to any one of paragraphs of 16 to 29, wherein the tall oil is oxidized to provide an ether bond between at least two or more hydrocarbon backbones.\",\n \"31.A method for making a drilling fluid, comprising: mixing an oil phase, an aqueous phase, and a spray dried emulsifier to produce a drilling fluid, wherein the spray dried emulsifier comprises a mixture of a tall oil and a triamide, wherein the triamide has the chemical formula: wherein: x, y, and z are integers independently selected from 1 to 10, R1 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl, R2 is H or independently selected for each [(CH2)xNR2(CH2)y] unit, wherein R4 is a C1-C3 alkylene or a C1-C3 alkylene alcohol, and wherein at least one R2 is and R3 is a C8-C20 alkyl, a C8-C20 alkenyl, a C8-C20 dialkenyl, or a C8-C20 alkynyl.\",\n \"32.The method according to paragraph 31, wherein the spray dried emulsifier is present in the drilling fluid in an amount of about 1 wt % to about 5 wt %, based on the weight of the oil phase, the aqueous phase, and the spray dried emulsifier.\",\n \"33.The method according to paragraph 31 or 32, wherein R4 is an ethanediyl group (—CH2CH2—).\",\n \"Certain embodiments and features have been described using a set of numerical upper limits and a set of numerical lower limits.\",\n \"It should be appreciated that ranges including the combination of any two values, e.g., the combination of any lower value with any upper value, the combination of any two lower values, and/or the combination of any two upper values are contemplated unless otherwise indicated.\",\n \"Certain lower limits, upper limits and ranges appear in one or more claims below.\",\n \"All numerical values are “about” or “approximately” the indicated value, and take into account experimental error and variations that would be expected by a person having ordinary skill in the art.\",\n \"Various terms have been defined above.\",\n \"To the extent a term used in a claim is not defined above, it should be given the broadest definition persons in the pertinent art have given that term as reflected in at least one printed publication or issued patent.\",\n \"Furthermore, all patents, test procedures, and other documents cited in this application are fully incorporated by reference to the extent such disclosure is not inconsistent with this application and for all jurisdictions in which such incorporation is permitted.\",\n \"While the foregoing is directed to embodiments of the present invention, other and further embodiments of the invention may be devised without departing from the basic scope thereof, and the scope thereof is determined by the claims that follow.\"\n ]\n]"},"source":{"kind":"string","value":"Patent_15871986"}}},{"rowIdx":4493974,"cells":{"text":{"kind":"list like","value":[["TOUCH PANEL AND FABRICATION METHOD THEREOF","A touch panel and a fabricating method thereof are provided in the instant disclosure.","The touch panel having a non-display area and a display area includes a shielding layer disposed on a side of a substrate and defining the non-display area on the substrate; a sensing electrode layer disposed on the substrate at the same side as the shielding layer, wherein at least one portion of the sensing electrode layer is disposed on a surface of the substrate in the display area; a first protecting layer disposed in the display area and covering the sensing electrode layer; and a second protecting layer disposed in the non-display area and covering the shielding layer.","By modifying the structure of the protecting layer, the height difference between the sensing electrode layer and the shielding layer may not cause the color difference due to the non-uniform protecting layer."],["1.A fabricating method of a touch panel, wherein the touch panel defines a display area and a non-display area, the method comprising: forming a shielding layer on a side of a substrate, wherein an area of the substrate covered by the shielding layer defines the non-display area; forming a sensing electrode layer at the same side as the shielding layer on the substrate, wherein at least a portion of the sensing electrode layer superimposes the display area; forming a first protecting layer at least on the display area to cover the sensing electrode layer; and forming a second protecting layer on non-display area to cover the shielding layer.","2.The fabricating method of the touch panel according to claim 1, wherein the first protecting layer is a refractive index compensating layer, and the second protecting layer is an attaching layer.","3.The fabricating method of the touch panel according to claim 1, wherein the first protecting layer further extends to the non-display area, and is formed on a surface of the second protecting layer.","4.The fabricating method of the touch panel according to claim 1, before forming the second protecting layer, further comprising: forming a signal transmitting layer on a surface of the shielding layer to electrically connect to the sensing electrode layer.","5.The fabricating method of the touch panel according to claim 1, wherein the sensing electrode layer further extends to the non-display area, and the sensing electrode layer is formed before formation of the shielding layer so that the sensing electrode layer is formed on a lower surface of the shielding layer.","6.The fabricating method of the touch panel according to claim 1, wherein the sensing electrode layer further extends to the non-display area, and the sensing electrode layer is formed after formation of the shielding layer so that the sensing electrode layer is formed on an upper surface of the shielding layer."],[" BACKGROUND OF THE INVENTION The present invention claims the priority of China Patent Application No.","201310216959.4 filed on Jun.","4, 2013, which is incorporated by reference in the present application in its entirety."],[" BRIEF SUMMARY OF THE INVENTION The object of the present invention is related to a touch panel and fabrication method thereof.","According to one of the present disclosure, by means of changing the structure of the protecting layer and adjusting the processes, the protecting layer having two portions is designed to deposit on the sensing electrode layer and the shielding layer respectively.","The two portions of the protecting layer are formed independently, and thus the non-uniform coating for each portion would not occur despite the existence of thickness difference between the shielding layer and the sensing electrode layer.","In order to achieve the aforementioned objects, according to an embodiment of the present invention, a touch panel is provided.","The touch panel defines a non-display area and a display area corresponding to the non-display area.","The touch panel includes a shielding layer disposed at a side of a substrate, wherein the substrate covered by the shielding layer defines the non-display area; a sensing electrode layer disposed on the substrate at the same side as the shielding layer, wherein at least a portion of the sensing electrode layer superimposes the display area; a first protecting layer disposed in the display area and covering the sensing electrode layer; and a second protecting layer, disposed in the non-display area and covering the shielding layer.","In another embodiment of the instant disclosure, a fabricating method of the touch panel is provided.","The touch panel defines a display area and a non-display area corresponding to the display area.","The method comprising: forming a shielding layer on a side of a substrate, wherein an area covered by the shielding layer defines the non-display area; forming a sensing electrode layer on the substrate at the same side as the shielding layer, wherein at least a portion of the sensing electrode layer superimposes the display area; forming a first protecting layer at least in the display area to cover the sensing electrode layer; and forming a second protecting layer in non-display area to cover the shielding layer.","As a result, the color difference may be avoided, and the factors reducing the transparency of the touch panel may be weakened in the instant disclosure.","In addition, the protecting layer of the instant disclosure has two different portions which may be made of different materials.","In addition to protection, the first protecting layer covers the sensing electrode layer and has a refractive index larger than or equal to that of the sensing electrode, and therefore the difference of the refractive indices is minimized.","In addition to protection, the second protecting layer, which correspondingly covers the shielding layer and the signal transmitting layer, also provides a reliable adhesion to the shielding layer.","Taken as a whole, the display quality of the touch panel can be improved.","In order to further the understanding regarding the present invention, the following embodiments are provided along with illustrations to facilitate the disclosure of the present invention."],["BACKGROUND OF THE INVENTION The present invention claims the priority of China Patent Application No.","201310216959.4 filed on Jun.","4, 2013, which is incorporated by reference in the present application in its entirety.","Field of the Invention The present invention relates to a touch panel technology; in particular, to a touch panel and a fabrication method thereof.","Description of Related Art As the development of the touch control technology, the touch panel has been widely used in various consumer electronic devices, such as smart phone, tablets, digital camera, e-book, MP3 player, and so on, which are portable electronic products.","The touch panel also can be applied to the display screen of the apparatus for operating and controlling.","The touch panel not only provides convenience of input operation to user, it also has the advantages in its thinner shape, the lighter weight and the price competitiveness.","The touch panel typically includes a substrate, a sensing electrode layer, a shielding layer and a protective layer.","The protective layer is formed on the both the sensing electrode layer and the shielding layer to protect the sensing electrode layer from the physical or chemical damage.","However, the thickness of the shielding layer is (about ten to hundred times) thicker than that of the sensing electrode layer.","There is a “step” formed between the shielding layer and the sensing electrode layer due to the thickness difference therebetween.","While the protective layer is formed on both of the shielding layer and the sensing electrode layer in the following process, the step would easily result in the non-uniformity of the protective layer, and the appearance of the color difference in the protective layer.","The color difference would impact the transparent property of the touch panel.","BRIEF SUMMARY OF THE INVENTION The object of the present invention is related to a touch panel and fabrication method thereof.","According to one of the present disclosure, by means of changing the structure of the protecting layer and adjusting the processes, the protecting layer having two portions is designed to deposit on the sensing electrode layer and the shielding layer respectively.","The two portions of the protecting layer are formed independently, and thus the non-uniform coating for each portion would not occur despite the existence of thickness difference between the shielding layer and the sensing electrode layer.","In order to achieve the aforementioned objects, according to an embodiment of the present invention, a touch panel is provided.","The touch panel defines a non-display area and a display area corresponding to the non-display area.","The touch panel includes a shielding layer disposed at a side of a substrate, wherein the substrate covered by the shielding layer defines the non-display area; a sensing electrode layer disposed on the substrate at the same side as the shielding layer, wherein at least a portion of the sensing electrode layer superimposes the display area; a first protecting layer disposed in the display area and covering the sensing electrode layer; and a second protecting layer, disposed in the non-display area and covering the shielding layer.","In another embodiment of the instant disclosure, a fabricating method of the touch panel is provided.","The touch panel defines a display area and a non-display area corresponding to the display area.","The method comprising: forming a shielding layer on a side of a substrate, wherein an area covered by the shielding layer defines the non-display area; forming a sensing electrode layer on the substrate at the same side as the shielding layer, wherein at least a portion of the sensing electrode layer superimposes the display area; forming a first protecting layer at least in the display area to cover the sensing electrode layer; and forming a second protecting layer in non-display area to cover the shielding layer.","As a result, the color difference may be avoided, and the factors reducing the transparency of the touch panel may be weakened in the instant disclosure.","In addition, the protecting layer of the instant disclosure has two different portions which may be made of different materials.","In addition to protection, the first protecting layer covers the sensing electrode layer and has a refractive index larger than or equal to that of the sensing electrode, and therefore the difference of the refractive indices is minimized.","In addition to protection, the second protecting layer, which correspondingly covers the shielding layer and the signal transmitting layer, also provides a reliable adhesion to the shielding layer.","Taken as a whole, the display quality of the touch panel can be improved.","In order to further the understanding regarding the present invention, the following embodiments are provided along with illustrations to facilitate the disclosure of the present invention.","BRIEF DESCRIPTION OF THE DRAWINGS FIG.","1 shows a cross-sectional view of a touch panel according to a first embodiment of the instant disclosure; FIG.","2 shows an enlarged perspective view showing the detail of the first protecting layer in FIG.","1; FIG.","3 shows a cross-sectional view of a touch panel according to a second embodiment of the instant disclosure; FIG.","4 shows a cross-sectional view of a touch panel according to a third embodiment of the instant disclosure; and FIG.","5 is flow chart of the fabrication method for touch panel according to an embodiment of the instant disclosure.","DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The aforementioned illustrations and following detailed descriptions are exemplary for the purpose of further explaining the scope of the present invention.","Other objectives and advantages related to the present invention will be illustrated in the subsequent descriptions and appended drawings.","The orientations of “upper” and “lower” of the touch panel in the description of the embodiments are only used to represent the relative position.","In the drawings of the instant disclosure, the “upper side” of the touch panel means it is the farthest side from a user, and the “lower side” of the touch panel means it is the nearest side from the user.","Moreover, the touch panel of the embodiment defines a non-display area and a display area.","In general, the non-display area may be allocated at least one peripheral side of the display area.","All of the embodiments of the instant disclosure are described in the condition of the non-display area surrounding the display area.","Please refer to FIG.","1.FIG.","1 shows a cross-sectional view of a touch panel according to a first embodiment of the instant disclosure.","The touch panel 100 of the present embodiment includes a substrate 110, a shielding layer 130, a sensing electrode layer 120, a first protecting layer 151 and a second protecting layer 152.The substrate 110 may be made of the transparent material, such as glass and the like.","The substrate 110 has a lower surface 110a and an upper surface 110b opposite thereto.","The lower surface 110a serves as the operating surface for a user.","The upper surface 110b is used to form each element of the touch panel 100 thereon, and the example will be explained in detail in the following description.","Furthermore, in the instant embodiment, the lower surface 110a of the substrate 110 may be processed by surface treatments, such as toughening, scratch-resistant process, anti-glare process, antimicrobial and/or anti-reflective process.","On top of supporting, the surface treatment of the lower surface 110a allows the substrate 110 to be protected.","The shielding layer 130 is disposed on the peripheral portion of the upper surface 110b of the substrate 110, and an area covered by the shielding layer 130 defines the non-display area 100B.","In the present embodiment, the shielding layer 130 is an opaque and insulating layer, such as the black or the other colors polyimide layer, or ink layer.","The shielding layer 130 may be formed by deposition, lithography and etching processes.","The sensing electrode layer 120 and the shielding layer 130 are configured on the same side of the substrate 110, i.e.","on the upper side.","At least a portion of the sensing electrode layer 120 is configured on the upper surface 110b of the substrate 110 and in the display area 100B to provide the touch sensitivity for a user.","Specifically, the sensing electrode layer 120 includes a plurality of first electrodes 121 arranged in rows, a plurality of second electrodes (not shown in FIG.","1) arranged in columns, and a plurality of connecting portions 124 connecting a pair of two immediately adjacent second electrodes (not shown) in the same column.","Every two immediately adjacent first electrodes 121 in the same row are connected to each other by one of the bridging portions 123.The sensing electrode layer 120 includes a plurality of insulating portions 122, each of which is sandwiched between a pair of the bridging portion 123 and connecting portion 124.The arrangement of the abovementioned elements (i.e., the first electrodes 121, the second electrodes, the connecting portions 123, the bridging portions and the insulating portions 124 of the sensing electrode layer 120) defines an etching area 120A and a non-etching area 120B on the sensing electrode layer 120.At least a portion of the first protecting layer 151 is arranged in display area 100B, and covers the sensing electrode layer 120 at the display area 100B to protect the sensing electrode layer 120 from the physical or chemical damage.","Of course, since the etching area 120A and non-etching area 120B are defined on the sensing electrode layer 120, the first protecting layer 151 not only covers the non-etching area 120B of the sensing electrode layer 120, but also covers a portion of the substrate 110 appeared from the etching area 120A.","The second protecting layer 152 is arranged at the non-display area 100B, and superimposes the shielding layer 130.Since the shielding layer 130 for defining the non-display area 100B surrounds the display area 100A, in the instant embodiment, the second protecting layer 152 may have the frame-like shape.","As the abovementioned embodiment, by specific designs for the first protecting layer 151 and the second protecting layer 152, the protecting layer 150, which is fabricated in the back-end processes in the whole structure of the touch panel 100, would not be extremely affected due to the thickness difference between the shielding layer 130 (with a thickness ranging between 1.5 μm to 20 μm) and the sensing electrode layer 120 (with a thickness ranging between 250 Å to 300 Å).","During the fabrication of the protecting layer 150, the color difference resulting from the non-uniform coating of the protecting layer 150 may be effectively avoided, and thus the factors reducing the transparency of the touch panel 100 may be weakened, and the manufacturing yield of the touch panel 100 may be increased.","For the further description, in the present embodiment, the sequence of the steps, i.e., forming the shielding layer 130 and then forming the sensing electrode layer 120, is just as an example.","Moreover, the sensing electrode layer 120 may further extend to top surface of the shielding layer 130, which is arranged in the non-display area 100B.In one embodiment, as shown in FIG.","1, the sensing electrode layer 120, which has a portion in the display area 100A and the other portions in the non-display area 100B, is fabricated in the same process.","In another embodiment, the portion in the non-display area 100B may be an independent connecting portion and manufactured by an additional process rather than the process for manufacturing the other portions in the display area 100A.","However, the aforementioned fabrications are not used for limiting the scope of the instant disclosure.","The touch panel 100 of the instant embodiment further includes a signal transmitting layer 160.The signal transmitting layer 160 is interposed between the shielding layer 130 and the second protecting layer 152, and electrically connected to the sensing electrode layer 120 for transmitting the signal between the sensing electrode layer 120 and an external controller (not shown).","As a result, in the instant embodiment, the second protecting layer 152 in the non-display area 100B may not only cover the shielding layer 130, but also cover the signal transmitting layer 160 to protect the signal transmitting layer 160 from the physical or chemical damage.","For example, the signal transmitting layer 160 is a stack of Mo/Al/Mo layers.","The Al layer sandwiched between these two Mo layers is so chemically reactive that the Al layer is easily oxidized and forms an insulating aluminum oxide film when the Al layer is exposed to the air.","It is hence the second protecting layer 152 which may isolate the signal transmitting layer 160 from the air to prevent the Al layer from the oxidation, and may reduce the probability of the explosion of the Al layer caused by the damage of the Mo layer.","It is worth mentioning that the first protecting layer 151 of the instant embodiment may be a refractive index compensating layer, and the second protecting layer 152 may be an attaching layer.","As a result, the first protecting layer 151 correspondingly covering on the sensing electrode layer 120 not only provides the function of protection, but also compensates and matches the refractive index of the sensing electrode layer 120 so that the etching lines formed between the etching area 120A and the non-etching area 120B on the sensing electrode layer 120 become visually invisible.","The second protecting layer 152 correspondingly covering the shielding layer 130 and the signal transmitting layer 160 also provides a reliable adhesion to the shielding layer 130 in addition to providing the function of the protection.","The refractive index compensating layer, in one embodiment, may be made of a material selected from a group consisting of the metal oxide, non-metal oxide, Si-based material and the combination thereof.","The refractive index compensating layer can be designed in single or multi layers in structure.","Given the refractive index of the refractive index compensating layer of the instant embodiment is n1, and the refractive index of the sensing electrode layer is n2.In this case, the refractive index n1 of the refractive index compensating layer is larger than or equal to the refractive index n2 of the sensing electrode layer in the instant embodiment.","Therefore, the difference of the refractive indices for visible light of the etching area 120A and the non-etching area 120B is minimized.","In addition, poor display quality due to different refractive indices may be avoided, and a better display quality of the touch panel 100 may be achieved.","Please refer to FIG.","2.FIG.","2 illustrates an enlarged perspective view showing the detail of the first protecting layer in FIG.","1.More specifically, the first protecting layer 151 of the instant embodiment includes a first refractive index layer 1511 and a second refractive index layer 1512, which makes the first protecting layer 151 to be composite multilayered while the first protecting layer 151 is designed to be the refractive index compensating layer.","The first refractive index layer 1511 covers on the sensing electrode layer 120, the second refractive index 1512 is disposed on the first refractive index layer 1511.In addition, with respect to the refractive index n1 of the refractive index compensating layer, which is composite multilayered, please further refer to the following description.","Given the refractive index of the first refractive index layer 1511 is n3, and the refractive index of the second refractive index layer 1512 is n4, wherein n3 and n4 meet the following equations (1)-(3): n3=sin a/sin b (1) n4=sin b/sin c (2) n3*n4=(sin a/sin b)*(sin b/sin c)=sin a/sin c (3) Thus, the refractive index n1 of the refractive index compensating layer, n3 and n4 meet the following equations: n3=n1*n2.By the stacking configuration of the first refractive index layer 1511 and the second refractive index layer 1512 in the instant embodiment, the refractive index of the refractive index compensating layer, which is composite multilayered, is larger than or equal to that of the sensing electrode layer 120 disposed in the display area 100B.","In one embodiment, the refractive index n3 of the first refractive index layer 1511 is less than the refractive index of the sensing electrode layer 120, and the refractive index n4 of the second refractive index layer 1512 is larger than the refractive index of the sensing electrode layer 120.Specifically, if the first electrode 121 and the second conductive pattern (not shown) of the sensing electrode layer 120 are patterned indium tin oxide (ITO) layers which have the refractive index of 1.86, the first refractive index layer 1511 would be a layer having smaller refractive index, for example, silicon dioxide (SiO2) layer having a refractive index of 1.46 with a thickness ranging between 30 nm to 50 nm.","The second refractive index layer 1512 may be a layer, the refractive index of which is larger than 1.86, for example, niobium pentoxide (Nb2O5) with a refractive index of 2.35 and a thickness ranging between 5 nm to 10 nm.","In another embodiment, the first refractive index layer 1511 is Nb2O5 layer, and the second refractive index layer 1512 is SiO2 layer.","In other words, the refractive index compensating layer being composite multilayered may be, for example, formed by a SiO2 layer and a Nb2O5 layer according to the refractive index of the sensing electrode layer 120 in practice.","The attaching layer, in one embodiment, is an organic material layer.","The properties of the material of the attaching layer are the same as or similar to that of the shielding layer 130, and the attaching layer thus produces a more reliable adhesion to the shielding layer 130.The attaching layer composed of the organic materials undergoes the cross-cut tape test (ASTM D3359-93), and the adhesion degree of the attaching layer to the shielding layer 130 is at least 4B.","The frequency of stripping is less than 5%.","Accordingly, the signal transmitting layer 160 disposed between the attaching layer and the shielding layer 130 may be completely protected and isolated from the air, and the probability of the oxidation of the signal transmitting layer 160 is reduced.","In one embodiment, the organic material may be a polyimide (PI) material, an ink material, an alcohol material or the combination thereof.","The compositions of the polyimide material include Silane and Polymethylmethacrylate (PMMA).","The compositions of the ink materials include the pigment, the resin and the auxiliary agent, wherein the pigment may be titanium dioxide or toner, and the auxiliary agent may be curing agent or thickening agent.","The alcohol materials may be ethylene glycol, propylene glycol, ethanol, isopryl alcohol or the combination thereof.","The adhesion of the attaching layer may be optimized by adjusting the content of each component to provide the better adherence for the shielding layer 130.For the following description, please refer to FIG.","3.FIG.","3 shows a cross-sectional view of a touch panel according to a second embodiment of the instant disclosure.","As shown in FIG.","3, the structure of the touch panel of the instant embodiment is substantially similar to the first embodiment as shown in FIG.","1.The difference is that, in the instant embodiment, the first protecting layer 151 further extends to the non-display area 100B, and is formed on the surface of the second protecting layer 152.As a result, the second protecting layer 152 may be protected from peeling off.","The first protecting layer 151 of the instant embodiment is completely formed on the surface of the second protecting layer 152.Of course, according to the demands for the practical design, the first protecting layer 151 also may be formed on only one portion of the second protecting layer 152, which is not intended to limit the scope of the invention.","Please refer to the FIG.","4.FIG.","4 shows a cross-sectional view of a touch panel according to a third embodiment of the instant disclosure.","As illustrated in FIG.","4, the structure of the touch panel of the instant embodiment is substantially similar to the first embodiment as shown in FIG.","1.In the instant embodiment, the difference is the stacking sequence of the sensing electrode layer 120 and the shielding layer 130 of the touch panel 100.In the instant embodiment, the sequence of the processes is designed for disposing the sensing electrode layer 120 and then forming the shielding layer 130.That is to say, the sensing electrode layer 120 in the non-display area 100B is formed on a lower surface of the shielding layer 130.However, based on the design of the structure of the instant embodiment, an opening is formed on the shielding layer 130 to allow electrical communication between the already formed sensing electrode layer 120 and the signal transmitting layer 160.Furthermore, the electrical connecting layer 140 is formed by filling the conductive material into the opening portion.","As a result, the sensing electrode layer 120 is electrically connected to the signal transmitting layer 160 by the electrical connecting layer 140 extending through the opening.","Please refer to the FIG.","5.FIG.","5 is flow chart of the fabrication method for touch panel according to an embodiment of the instant disclosure.","Firstly, in step S1, a substrate is provided.","In step S2, a shielding layer is formed at a side of the substrate, and an area of the substrate covered by the shielding layer 130 defines the non-display area 100B of the touch panel.","In step S3, a sensing electrode layer is formed on the substrate at the same side as the shielding layer.","In the instant embodiment, there is at least one portion of the sensing electrode layer formed on the surface of the substrate and in the display area of the touch panel, besides, the sensing electrode layer further extends to the non-display area and is arranged on the upper surface of the shielding layer in the non-display area formed in step S2.Of course, in another embodiment, the order of the above step S2 and the above step S3 can also be exchanged.","That is to say, the sensing electrode is formed, and the shielding layer is subsequently formed.","It is thus the sensing electrode layer extending to the non-display area is arranged on the lower surface of the shielding layer.","In step S4, a signal transmitting layer is formed on the shielding layer to electrically connect to the sensing electrode layer.","In step S5, a first protecting layer is at least formed in the display area to cover the sensing electrode layer.","In step S6, a second protecting layer is formed to cover the shielding layer and the signal transmitting layer in the non-display area.","The touch panel of the instant embodiment could be fabricated by performing the aforementioned steps.","In another embodiment, the order of the abovementioned step S5 and step S6 can also be exchanged.","That is to say, the second protecting layer can be formed, and thereafter the first protecting layer is formed.","As a result, the first protecting layer can be designed to be not merely formed in the display area, but extend to the surface of the second protecting layer in the non-display area so as to prevent the second protecting layer from peeling off At last, additional explanations may be provided.","In each of the abovementioned embodiments, the insulating portion can be made by coating, lithography and etching processes, which are performed in sequence.","Besides, the insulating portion is made of for example epoxy layer, polyimide layer or methyl methacrylate layer and so on.","Additionally, the first electrode, the second electrode or the signal transmitting layer also may be manufactured by the deposition, the lithography, the etching processes and so on.","The aforementioned deposition process for example physical vapor deposition (PVD) or chemical vapor deposition (CVD).","The physical vapor deposition (PVD) is such as evaporation or sputtering deposition, and the chemical vapor deposition is such as low pressure chemical vapor deposition (LPCVD), metal-organic chemical vapor deposition (MOCVD), plasma-enhanced chemical vapor deposition (PECVD) or photo chemical vapor deposition (PHOTO CVD).","The aforementioned etching process may be chemical etching or laser etching process.","Furthermore, the first electrode and the second electrode of the aforementioned embodiments may be made of the transparent conductive material.","The transparent conductive material such as indium tin oxide (ITO), indium zinc oxide (IZO), cadmium tin oxide (CTO), aluminum zinc oxide (AZO), indium tin zinc oxide (ITZO), zinc oxide, cadmium oxide, hafnium oxide (HfO), indium gallium zinc oxide (InGaZnO), indium gallium zinc magnesium oxide (InGaZnMgO), indium gallium magnesium oxide (InGaMgO) or indium gallium aluminum oxide (InGaAlO) and the like.","Besides, the signal transmitting layer 160 may be made of Au, Ag, Cu, Ni, Al, Cr or the combination thereof, for example, the structure of the signal transmitting layer 160 is a Mo/Al/Mo stack, wherein the Al layer is sandwiched between the two Mo layers.","In summary, the color difference may be avoided, and the factors reducing the transparency of the touch panel may be weakened.","In addition, the protecting layer has two different portions which may be made of different materials.","In addition to protection, the first protecting layer covers the sensing electrode layer and has a refractive index larger than or equal to that of the sensing electrode, and therefore the difference of the refractive indices is minimized.","In addition to protection, the second protecting layer, which correspondingly covers the shielding layer, provides a reliable adhesion to the shielding layer.","Taken as a whole, the display quality of the touch panel can be improved.","The descriptions illustrated supra set forth simplify the preferred embodiments of the present invention; however, the characteristics of the present invention are by no means restricted thereto.","All changes, alterations, or modifications conveniently considered by those skilled in the art are deemed to be encompassed within the scope of the present invention delineated by the following claims."]],"string":"[\n [\n \"TOUCH PANEL AND FABRICATION METHOD THEREOF\",\n \"A touch panel and a fabricating method thereof are provided in the instant disclosure.\",\n \"The touch panel having a non-display area and a display area includes a shielding layer disposed on a side of a substrate and defining the non-display area on the substrate; a sensing electrode layer disposed on the substrate at the same side as the shielding layer, wherein at least one portion of the sensing electrode layer is disposed on a surface of the substrate in the display area; a first protecting layer disposed in the display area and covering the sensing electrode layer; and a second protecting layer disposed in the non-display area and covering the shielding layer.\",\n \"By modifying the structure of the protecting layer, the height difference between the sensing electrode layer and the shielding layer may not cause the color difference due to the non-uniform protecting layer.\"\n ],\n [\n \"1.A fabricating method of a touch panel, wherein the touch panel defines a display area and a non-display area, the method comprising: forming a shielding layer on a side of a substrate, wherein an area of the substrate covered by the shielding layer defines the non-display area; forming a sensing electrode layer at the same side as the shielding layer on the substrate, wherein at least a portion of the sensing electrode layer superimposes the display area; forming a first protecting layer at least on the display area to cover the sensing electrode layer; and forming a second protecting layer on non-display area to cover the shielding layer.\",\n \"2.The fabricating method of the touch panel according to claim 1, wherein the first protecting layer is a refractive index compensating layer, and the second protecting layer is an attaching layer.\",\n \"3.The fabricating method of the touch panel according to claim 1, wherein the first protecting layer further extends to the non-display area, and is formed on a surface of the second protecting layer.\",\n \"4.The fabricating method of the touch panel according to claim 1, before forming the second protecting layer, further comprising: forming a signal transmitting layer on a surface of the shielding layer to electrically connect to the sensing electrode layer.\",\n \"5.The fabricating method of the touch panel according to claim 1, wherein the sensing electrode layer further extends to the non-display area, and the sensing electrode layer is formed before formation of the shielding layer so that the sensing electrode layer is formed on a lower surface of the shielding layer.\",\n \"6.The fabricating method of the touch panel according to claim 1, wherein the sensing electrode layer further extends to the non-display area, and the sensing electrode layer is formed after formation of the shielding layer so that the sensing electrode layer is formed on an upper surface of the shielding layer.\"\n ],\n [\n \" BACKGROUND OF THE INVENTION The present invention claims the priority of China Patent Application No.\",\n \"201310216959.4 filed on Jun.\",\n \"4, 2013, which is incorporated by reference in the present application in its entirety.\"\n ],\n [\n \" BRIEF SUMMARY OF THE INVENTION The object of the present invention is related to a touch panel and fabrication method thereof.\",\n \"According to one of the present disclosure, by means of changing the structure of the protecting layer and adjusting the processes, the protecting layer having two portions is designed to deposit on the sensing electrode layer and the shielding layer respectively.\",\n \"The two portions of the protecting layer are formed independently, and thus the non-uniform coating for each portion would not occur despite the existence of thickness difference between the shielding layer and the sensing electrode layer.\",\n \"In order to achieve the aforementioned objects, according to an embodiment of the present invention, a touch panel is provided.\",\n \"The touch panel defines a non-display area and a display area corresponding to the non-display area.\",\n \"The touch panel includes a shielding layer disposed at a side of a substrate, wherein the substrate covered by the shielding layer defines the non-display area; a sensing electrode layer disposed on the substrate at the same side as the shielding layer, wherein at least a portion of the sensing electrode layer superimposes the display area; a first protecting layer disposed in the display area and covering the sensing electrode layer; and a second protecting layer, disposed in the non-display area and covering the shielding layer.\",\n \"In another embodiment of the instant disclosure, a fabricating method of the touch panel is provided.\",\n \"The touch panel defines a display area and a non-display area corresponding to the display area.\",\n \"The method comprising: forming a shielding layer on a side of a substrate, wherein an area covered by the shielding layer defines the non-display area; forming a sensing electrode layer on the substrate at the same side as the shielding layer, wherein at least a portion of the sensing electrode layer superimposes the display area; forming a first protecting layer at least in the display area to cover the sensing electrode layer; and forming a second protecting layer in non-display area to cover the shielding layer.\",\n \"As a result, the color difference may be avoided, and the factors reducing the transparency of the touch panel may be weakened in the instant disclosure.\",\n \"In addition, the protecting layer of the instant disclosure has two different portions which may be made of different materials.\",\n \"In addition to protection, the first protecting layer covers the sensing electrode layer and has a refractive index larger than or equal to that of the sensing electrode, and therefore the difference of the refractive indices is minimized.\",\n \"In addition to protection, the second protecting layer, which correspondingly covers the shielding layer and the signal transmitting layer, also provides a reliable adhesion to the shielding layer.\",\n \"Taken as a whole, the display quality of the touch panel can be improved.\",\n \"In order to further the understanding regarding the present invention, the following embodiments are provided along with illustrations to facilitate the disclosure of the present invention.\"\n ],\n [\n \"BACKGROUND OF THE INVENTION The present invention claims the priority of China Patent Application No.\",\n \"201310216959.4 filed on Jun.\",\n \"4, 2013, which is incorporated by reference in the present application in its entirety.\",\n \"Field of the Invention The present invention relates to a touch panel technology; in particular, to a touch panel and a fabrication method thereof.\",\n \"Description of Related Art As the development of the touch control technology, the touch panel has been widely used in various consumer electronic devices, such as smart phone, tablets, digital camera, e-book, MP3 player, and so on, which are portable electronic products.\",\n \"The touch panel also can be applied to the display screen of the apparatus for operating and controlling.\",\n \"The touch panel not only provides convenience of input operation to user, it also has the advantages in its thinner shape, the lighter weight and the price competitiveness.\",\n \"The touch panel typically includes a substrate, a sensing electrode layer, a shielding layer and a protective layer.\",\n \"The protective layer is formed on the both the sensing electrode layer and the shielding layer to protect the sensing electrode layer from the physical or chemical damage.\",\n \"However, the thickness of the shielding layer is (about ten to hundred times) thicker than that of the sensing electrode layer.\",\n \"There is a “step” formed between the shielding layer and the sensing electrode layer due to the thickness difference therebetween.\",\n \"While the protective layer is formed on both of the shielding layer and the sensing electrode layer in the following process, the step would easily result in the non-uniformity of the protective layer, and the appearance of the color difference in the protective layer.\",\n \"The color difference would impact the transparent property of the touch panel.\",\n \"BRIEF SUMMARY OF THE INVENTION The object of the present invention is related to a touch panel and fabrication method thereof.\",\n \"According to one of the present disclosure, by means of changing the structure of the protecting layer and adjusting the processes, the protecting layer having two portions is designed to deposit on the sensing electrode layer and the shielding layer respectively.\",\n \"The two portions of the protecting layer are formed independently, and thus the non-uniform coating for each portion would not occur despite the existence of thickness difference between the shielding layer and the sensing electrode layer.\",\n \"In order to achieve the aforementioned objects, according to an embodiment of the present invention, a touch panel is provided.\",\n \"The touch panel defines a non-display area and a display area corresponding to the non-display area.\",\n \"The touch panel includes a shielding layer disposed at a side of a substrate, wherein the substrate covered by the shielding layer defines the non-display area; a sensing electrode layer disposed on the substrate at the same side as the shielding layer, wherein at least a portion of the sensing electrode layer superimposes the display area; a first protecting layer disposed in the display area and covering the sensing electrode layer; and a second protecting layer, disposed in the non-display area and covering the shielding layer.\",\n \"In another embodiment of the instant disclosure, a fabricating method of the touch panel is provided.\",\n \"The touch panel defines a display area and a non-display area corresponding to the display area.\",\n \"The method comprising: forming a shielding layer on a side of a substrate, wherein an area covered by the shielding layer defines the non-display area; forming a sensing electrode layer on the substrate at the same side as the shielding layer, wherein at least a portion of the sensing electrode layer superimposes the display area; forming a first protecting layer at least in the display area to cover the sensing electrode layer; and forming a second protecting layer in non-display area to cover the shielding layer.\",\n \"As a result, the color difference may be avoided, and the factors reducing the transparency of the touch panel may be weakened in the instant disclosure.\",\n \"In addition, the protecting layer of the instant disclosure has two different portions which may be made of different materials.\",\n \"In addition to protection, the first protecting layer covers the sensing electrode layer and has a refractive index larger than or equal to that of the sensing electrode, and therefore the difference of the refractive indices is minimized.\",\n \"In addition to protection, the second protecting layer, which correspondingly covers the shielding layer and the signal transmitting layer, also provides a reliable adhesion to the shielding layer.\",\n \"Taken as a whole, the display quality of the touch panel can be improved.\",\n \"In order to further the understanding regarding the present invention, the following embodiments are provided along with illustrations to facilitate the disclosure of the present invention.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS FIG.\",\n \"1 shows a cross-sectional view of a touch panel according to a first embodiment of the instant disclosure; FIG.\",\n \"2 shows an enlarged perspective view showing the detail of the first protecting layer in FIG.\",\n \"1; FIG.\",\n \"3 shows a cross-sectional view of a touch panel according to a second embodiment of the instant disclosure; FIG.\",\n \"4 shows a cross-sectional view of a touch panel according to a third embodiment of the instant disclosure; and FIG.\",\n \"5 is flow chart of the fabrication method for touch panel according to an embodiment of the instant disclosure.\",\n \"DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The aforementioned illustrations and following detailed descriptions are exemplary for the purpose of further explaining the scope of the present invention.\",\n \"Other objectives and advantages related to the present invention will be illustrated in the subsequent descriptions and appended drawings.\",\n \"The orientations of “upper” and “lower” of the touch panel in the description of the embodiments are only used to represent the relative position.\",\n \"In the drawings of the instant disclosure, the “upper side” of the touch panel means it is the farthest side from a user, and the “lower side” of the touch panel means it is the nearest side from the user.\",\n \"Moreover, the touch panel of the embodiment defines a non-display area and a display area.\",\n \"In general, the non-display area may be allocated at least one peripheral side of the display area.\",\n \"All of the embodiments of the instant disclosure are described in the condition of the non-display area surrounding the display area.\",\n \"Please refer to FIG.\",\n \"1.FIG.\",\n \"1 shows a cross-sectional view of a touch panel according to a first embodiment of the instant disclosure.\",\n \"The touch panel 100 of the present embodiment includes a substrate 110, a shielding layer 130, a sensing electrode layer 120, a first protecting layer 151 and a second protecting layer 152.The substrate 110 may be made of the transparent material, such as glass and the like.\",\n \"The substrate 110 has a lower surface 110a and an upper surface 110b opposite thereto.\",\n \"The lower surface 110a serves as the operating surface for a user.\",\n \"The upper surface 110b is used to form each element of the touch panel 100 thereon, and the example will be explained in detail in the following description.\",\n \"Furthermore, in the instant embodiment, the lower surface 110a of the substrate 110 may be processed by surface treatments, such as toughening, scratch-resistant process, anti-glare process, antimicrobial and/or anti-reflective process.\",\n \"On top of supporting, the surface treatment of the lower surface 110a allows the substrate 110 to be protected.\",\n \"The shielding layer 130 is disposed on the peripheral portion of the upper surface 110b of the substrate 110, and an area covered by the shielding layer 130 defines the non-display area 100B.\",\n \"In the present embodiment, the shielding layer 130 is an opaque and insulating layer, such as the black or the other colors polyimide layer, or ink layer.\",\n \"The shielding layer 130 may be formed by deposition, lithography and etching processes.\",\n \"The sensing electrode layer 120 and the shielding layer 130 are configured on the same side of the substrate 110, i.e.\",\n \"on the upper side.\",\n \"At least a portion of the sensing electrode layer 120 is configured on the upper surface 110b of the substrate 110 and in the display area 100B to provide the touch sensitivity for a user.\",\n \"Specifically, the sensing electrode layer 120 includes a plurality of first electrodes 121 arranged in rows, a plurality of second electrodes (not shown in FIG.\",\n \"1) arranged in columns, and a plurality of connecting portions 124 connecting a pair of two immediately adjacent second electrodes (not shown) in the same column.\",\n \"Every two immediately adjacent first electrodes 121 in the same row are connected to each other by one of the bridging portions 123.The sensing electrode layer 120 includes a plurality of insulating portions 122, each of which is sandwiched between a pair of the bridging portion 123 and connecting portion 124.The arrangement of the abovementioned elements (i.e., the first electrodes 121, the second electrodes, the connecting portions 123, the bridging portions and the insulating portions 124 of the sensing electrode layer 120) defines an etching area 120A and a non-etching area 120B on the sensing electrode layer 120.At least a portion of the first protecting layer 151 is arranged in display area 100B, and covers the sensing electrode layer 120 at the display area 100B to protect the sensing electrode layer 120 from the physical or chemical damage.\",\n \"Of course, since the etching area 120A and non-etching area 120B are defined on the sensing electrode layer 120, the first protecting layer 151 not only covers the non-etching area 120B of the sensing electrode layer 120, but also covers a portion of the substrate 110 appeared from the etching area 120A.\",\n \"The second protecting layer 152 is arranged at the non-display area 100B, and superimposes the shielding layer 130.Since the shielding layer 130 for defining the non-display area 100B surrounds the display area 100A, in the instant embodiment, the second protecting layer 152 may have the frame-like shape.\",\n \"As the abovementioned embodiment, by specific designs for the first protecting layer 151 and the second protecting layer 152, the protecting layer 150, which is fabricated in the back-end processes in the whole structure of the touch panel 100, would not be extremely affected due to the thickness difference between the shielding layer 130 (with a thickness ranging between 1.5 μm to 20 μm) and the sensing electrode layer 120 (with a thickness ranging between 250 Å to 300 Å).\",\n \"During the fabrication of the protecting layer 150, the color difference resulting from the non-uniform coating of the protecting layer 150 may be effectively avoided, and thus the factors reducing the transparency of the touch panel 100 may be weakened, and the manufacturing yield of the touch panel 100 may be increased.\",\n \"For the further description, in the present embodiment, the sequence of the steps, i.e., forming the shielding layer 130 and then forming the sensing electrode layer 120, is just as an example.\",\n \"Moreover, the sensing electrode layer 120 may further extend to top surface of the shielding layer 130, which is arranged in the non-display area 100B.In one embodiment, as shown in FIG.\",\n \"1, the sensing electrode layer 120, which has a portion in the display area 100A and the other portions in the non-display area 100B, is fabricated in the same process.\",\n \"In another embodiment, the portion in the non-display area 100B may be an independent connecting portion and manufactured by an additional process rather than the process for manufacturing the other portions in the display area 100A.\",\n \"However, the aforementioned fabrications are not used for limiting the scope of the instant disclosure.\",\n \"The touch panel 100 of the instant embodiment further includes a signal transmitting layer 160.The signal transmitting layer 160 is interposed between the shielding layer 130 and the second protecting layer 152, and electrically connected to the sensing electrode layer 120 for transmitting the signal between the sensing electrode layer 120 and an external controller (not shown).\",\n \"As a result, in the instant embodiment, the second protecting layer 152 in the non-display area 100B may not only cover the shielding layer 130, but also cover the signal transmitting layer 160 to protect the signal transmitting layer 160 from the physical or chemical damage.\",\n \"For example, the signal transmitting layer 160 is a stack of Mo/Al/Mo layers.\",\n \"The Al layer sandwiched between these two Mo layers is so chemically reactive that the Al layer is easily oxidized and forms an insulating aluminum oxide film when the Al layer is exposed to the air.\",\n \"It is hence the second protecting layer 152 which may isolate the signal transmitting layer 160 from the air to prevent the Al layer from the oxidation, and may reduce the probability of the explosion of the Al layer caused by the damage of the Mo layer.\",\n \"It is worth mentioning that the first protecting layer 151 of the instant embodiment may be a refractive index compensating layer, and the second protecting layer 152 may be an attaching layer.\",\n \"As a result, the first protecting layer 151 correspondingly covering on the sensing electrode layer 120 not only provides the function of protection, but also compensates and matches the refractive index of the sensing electrode layer 120 so that the etching lines formed between the etching area 120A and the non-etching area 120B on the sensing electrode layer 120 become visually invisible.\",\n \"The second protecting layer 152 correspondingly covering the shielding layer 130 and the signal transmitting layer 160 also provides a reliable adhesion to the shielding layer 130 in addition to providing the function of the protection.\",\n \"The refractive index compensating layer, in one embodiment, may be made of a material selected from a group consisting of the metal oxide, non-metal oxide, Si-based material and the combination thereof.\",\n \"The refractive index compensating layer can be designed in single or multi layers in structure.\",\n \"Given the refractive index of the refractive index compensating layer of the instant embodiment is n1, and the refractive index of the sensing electrode layer is n2.In this case, the refractive index n1 of the refractive index compensating layer is larger than or equal to the refractive index n2 of the sensing electrode layer in the instant embodiment.\",\n \"Therefore, the difference of the refractive indices for visible light of the etching area 120A and the non-etching area 120B is minimized.\",\n \"In addition, poor display quality due to different refractive indices may be avoided, and a better display quality of the touch panel 100 may be achieved.\",\n \"Please refer to FIG.\",\n \"2.FIG.\",\n \"2 illustrates an enlarged perspective view showing the detail of the first protecting layer in FIG.\",\n \"1.More specifically, the first protecting layer 151 of the instant embodiment includes a first refractive index layer 1511 and a second refractive index layer 1512, which makes the first protecting layer 151 to be composite multilayered while the first protecting layer 151 is designed to be the refractive index compensating layer.\",\n \"The first refractive index layer 1511 covers on the sensing electrode layer 120, the second refractive index 1512 is disposed on the first refractive index layer 1511.In addition, with respect to the refractive index n1 of the refractive index compensating layer, which is composite multilayered, please further refer to the following description.\",\n \"Given the refractive index of the first refractive index layer 1511 is n3, and the refractive index of the second refractive index layer 1512 is n4, wherein n3 and n4 meet the following equations (1)-(3): n3=sin a/sin b (1) n4=sin b/sin c (2) n3*n4=(sin a/sin b)*(sin b/sin c)=sin a/sin c (3) Thus, the refractive index n1 of the refractive index compensating layer, n3 and n4 meet the following equations: n3=n1*n2.By the stacking configuration of the first refractive index layer 1511 and the second refractive index layer 1512 in the instant embodiment, the refractive index of the refractive index compensating layer, which is composite multilayered, is larger than or equal to that of the sensing electrode layer 120 disposed in the display area 100B.\",\n \"In one embodiment, the refractive index n3 of the first refractive index layer 1511 is less than the refractive index of the sensing electrode layer 120, and the refractive index n4 of the second refractive index layer 1512 is larger than the refractive index of the sensing electrode layer 120.Specifically, if the first electrode 121 and the second conductive pattern (not shown) of the sensing electrode layer 120 are patterned indium tin oxide (ITO) layers which have the refractive index of 1.86, the first refractive index layer 1511 would be a layer having smaller refractive index, for example, silicon dioxide (SiO2) layer having a refractive index of 1.46 with a thickness ranging between 30 nm to 50 nm.\",\n \"The second refractive index layer 1512 may be a layer, the refractive index of which is larger than 1.86, for example, niobium pentoxide (Nb2O5) with a refractive index of 2.35 and a thickness ranging between 5 nm to 10 nm.\",\n \"In another embodiment, the first refractive index layer 1511 is Nb2O5 layer, and the second refractive index layer 1512 is SiO2 layer.\",\n \"In other words, the refractive index compensating layer being composite multilayered may be, for example, formed by a SiO2 layer and a Nb2O5 layer according to the refractive index of the sensing electrode layer 120 in practice.\",\n \"The attaching layer, in one embodiment, is an organic material layer.\",\n \"The properties of the material of the attaching layer are the same as or similar to that of the shielding layer 130, and the attaching layer thus produces a more reliable adhesion to the shielding layer 130.The attaching layer composed of the organic materials undergoes the cross-cut tape test (ASTM D3359-93), and the adhesion degree of the attaching layer to the shielding layer 130 is at least 4B.\",\n \"The frequency of stripping is less than 5%.\",\n \"Accordingly, the signal transmitting layer 160 disposed between the attaching layer and the shielding layer 130 may be completely protected and isolated from the air, and the probability of the oxidation of the signal transmitting layer 160 is reduced.\",\n \"In one embodiment, the organic material may be a polyimide (PI) material, an ink material, an alcohol material or the combination thereof.\",\n \"The compositions of the polyimide material include Silane and Polymethylmethacrylate (PMMA).\",\n \"The compositions of the ink materials include the pigment, the resin and the auxiliary agent, wherein the pigment may be titanium dioxide or toner, and the auxiliary agent may be curing agent or thickening agent.\",\n \"The alcohol materials may be ethylene glycol, propylene glycol, ethanol, isopryl alcohol or the combination thereof.\",\n \"The adhesion of the attaching layer may be optimized by adjusting the content of each component to provide the better adherence for the shielding layer 130.For the following description, please refer to FIG.\",\n \"3.FIG.\",\n \"3 shows a cross-sectional view of a touch panel according to a second embodiment of the instant disclosure.\",\n \"As shown in FIG.\",\n \"3, the structure of the touch panel of the instant embodiment is substantially similar to the first embodiment as shown in FIG.\",\n \"1.The difference is that, in the instant embodiment, the first protecting layer 151 further extends to the non-display area 100B, and is formed on the surface of the second protecting layer 152.As a result, the second protecting layer 152 may be protected from peeling off.\",\n \"The first protecting layer 151 of the instant embodiment is completely formed on the surface of the second protecting layer 152.Of course, according to the demands for the practical design, the first protecting layer 151 also may be formed on only one portion of the second protecting layer 152, which is not intended to limit the scope of the invention.\",\n \"Please refer to the FIG.\",\n \"4.FIG.\",\n \"4 shows a cross-sectional view of a touch panel according to a third embodiment of the instant disclosure.\",\n \"As illustrated in FIG.\",\n \"4, the structure of the touch panel of the instant embodiment is substantially similar to the first embodiment as shown in FIG.\",\n \"1.In the instant embodiment, the difference is the stacking sequence of the sensing electrode layer 120 and the shielding layer 130 of the touch panel 100.In the instant embodiment, the sequence of the processes is designed for disposing the sensing electrode layer 120 and then forming the shielding layer 130.That is to say, the sensing electrode layer 120 in the non-display area 100B is formed on a lower surface of the shielding layer 130.However, based on the design of the structure of the instant embodiment, an opening is formed on the shielding layer 130 to allow electrical communication between the already formed sensing electrode layer 120 and the signal transmitting layer 160.Furthermore, the electrical connecting layer 140 is formed by filling the conductive material into the opening portion.\",\n \"As a result, the sensing electrode layer 120 is electrically connected to the signal transmitting layer 160 by the electrical connecting layer 140 extending through the opening.\",\n \"Please refer to the FIG.\",\n \"5.FIG.\",\n \"5 is flow chart of the fabrication method for touch panel according to an embodiment of the instant disclosure.\",\n \"Firstly, in step S1, a substrate is provided.\",\n \"In step S2, a shielding layer is formed at a side of the substrate, and an area of the substrate covered by the shielding layer 130 defines the non-display area 100B of the touch panel.\",\n \"In step S3, a sensing electrode layer is formed on the substrate at the same side as the shielding layer.\",\n \"In the instant embodiment, there is at least one portion of the sensing electrode layer formed on the surface of the substrate and in the display area of the touch panel, besides, the sensing electrode layer further extends to the non-display area and is arranged on the upper surface of the shielding layer in the non-display area formed in step S2.Of course, in another embodiment, the order of the above step S2 and the above step S3 can also be exchanged.\",\n \"That is to say, the sensing electrode is formed, and the shielding layer is subsequently formed.\",\n \"It is thus the sensing electrode layer extending to the non-display area is arranged on the lower surface of the shielding layer.\",\n \"In step S4, a signal transmitting layer is formed on the shielding layer to electrically connect to the sensing electrode layer.\",\n \"In step S5, a first protecting layer is at least formed in the display area to cover the sensing electrode layer.\",\n \"In step S6, a second protecting layer is formed to cover the shielding layer and the signal transmitting layer in the non-display area.\",\n \"The touch panel of the instant embodiment could be fabricated by performing the aforementioned steps.\",\n \"In another embodiment, the order of the abovementioned step S5 and step S6 can also be exchanged.\",\n \"That is to say, the second protecting layer can be formed, and thereafter the first protecting layer is formed.\",\n \"As a result, the first protecting layer can be designed to be not merely formed in the display area, but extend to the surface of the second protecting layer in the non-display area so as to prevent the second protecting layer from peeling off At last, additional explanations may be provided.\",\n \"In each of the abovementioned embodiments, the insulating portion can be made by coating, lithography and etching processes, which are performed in sequence.\",\n \"Besides, the insulating portion is made of for example epoxy layer, polyimide layer or methyl methacrylate layer and so on.\",\n \"Additionally, the first electrode, the second electrode or the signal transmitting layer also may be manufactured by the deposition, the lithography, the etching processes and so on.\",\n \"The aforementioned deposition process for example physical vapor deposition (PVD) or chemical vapor deposition (CVD).\",\n \"The physical vapor deposition (PVD) is such as evaporation or sputtering deposition, and the chemical vapor deposition is such as low pressure chemical vapor deposition (LPCVD), metal-organic chemical vapor deposition (MOCVD), plasma-enhanced chemical vapor deposition (PECVD) or photo chemical vapor deposition (PHOTO CVD).\",\n \"The aforementioned etching process may be chemical etching or laser etching process.\",\n \"Furthermore, the first electrode and the second electrode of the aforementioned embodiments may be made of the transparent conductive material.\",\n \"The transparent conductive material such as indium tin oxide (ITO), indium zinc oxide (IZO), cadmium tin oxide (CTO), aluminum zinc oxide (AZO), indium tin zinc oxide (ITZO), zinc oxide, cadmium oxide, hafnium oxide (HfO), indium gallium zinc oxide (InGaZnO), indium gallium zinc magnesium oxide (InGaZnMgO), indium gallium magnesium oxide (InGaMgO) or indium gallium aluminum oxide (InGaAlO) and the like.\",\n \"Besides, the signal transmitting layer 160 may be made of Au, Ag, Cu, Ni, Al, Cr or the combination thereof, for example, the structure of the signal transmitting layer 160 is a Mo/Al/Mo stack, wherein the Al layer is sandwiched between the two Mo layers.\",\n \"In summary, the color difference may be avoided, and the factors reducing the transparency of the touch panel may be weakened.\",\n \"In addition, the protecting layer has two different portions which may be made of different materials.\",\n \"In addition to protection, the first protecting layer covers the sensing electrode layer and has a refractive index larger than or equal to that of the sensing electrode, and therefore the difference of the refractive indices is minimized.\",\n \"In addition to protection, the second protecting layer, which correspondingly covers the shielding layer, provides a reliable adhesion to the shielding layer.\",\n \"Taken as a whole, the display quality of the touch panel can be improved.\",\n \"The descriptions illustrated supra set forth simplify the preferred embodiments of the present invention; however, the characteristics of the present invention are by no means restricted thereto.\",\n \"All changes, alterations, or modifications conveniently considered by those skilled in the art are deemed to be encompassed within the scope of the present invention delineated by the following claims.\"\n ]\n]"},"source":{"kind":"string","value":"Patent_15871987"}}},{"rowIdx":4493975,"cells":{"text":{"kind":"list like","value":[["Single Image Sensor for Capturing Mixed Structured-light Images and Regular Images","An integrated image sensor for capturing a mixed structured-light image and regular image using an integrated image sensor are disclosed.","The integrated image sensor comprises a pixel array, one or more output circuits, one or more analog-to-digital converters, and one or more timing and control circuits.","The timing and control circuits are arranged to perform a set of actions including capturing a regular image and a structured-light image.","According to the present invention, the structured-light image captured before or after the regular image is used to derive depth or shape information for the regular image.","An endoscope based on the above integrated image sensor is also disclosed.","The endoscope may comprises a capsule housing adapted to be swallowed, where the components of integrated image sensor, a structured light source and a non-structured light source are enclosed and sealed in the capsule housing."],["1.An integrated image sensor, comprising: a pixel array being responsive to light energy received by the pixel array to produce pixel signals having a voltage level depending on the light energy received by the pixel array; one or more output circuits coupled to the pixel array to access the pixel signals produced by the pixel array; one or more analog-to-digital converters having a first dynamic range and a second dynamic range; one or more timing and control circuits coupled to the pixel array, said one or more output circuits, said one or more analog-to-digital converters or a combination thereof, wherein said one or more timing and control circuits are arranged to: capture, by the pixel array, a structured-light image formed on a common image plane during a first frame period by applying first reset signals to the pixel array to reset rows of pixels of the pixel array, exposing the rows of pixels of the pixel array to structured light to cause first analog signals from the rows of pixels, and converting the first analog signals from the rows of pixels of the pixel array into first digital outputs for the structured-light image using one or more analog-to-digital converters; and capture, by the pixel array, a regular image formed on the common image plane during a second frame period longer than the first frame period by applying second reset signals to the pixel array to reset the rows of pixels of the pixel array, exposing the rows of pixels to non-structured light to cause second analog signals from the rows of pixels, and converting the second analog signals from the rows of pixels into second digital outputs for the regular image using said one or more analog-to-digital converters; and wherein the structured-light image is captured before or after the regular image to derive depth or shape information for the regular image.","2.The integrated image sensor of claim 1, wherein said one or more analog-to-digital converters correspond to a configurable analog-to-digital converter to provide both the first dynamic range and the second dynamic range.","3.The integrated image sensor of claim 1, wherein said one or more analog-to-digital converters correspond to two analog-to-digital converters with two different resolutions to provide both the first dynamic range and the second dynamic range.","4.The integrated image sensor of claim 1, wherein said one or more timing and control circuits are further arranged to cause the structured-light image to be captured at lower spatial resolution than the regular image.","5.An endoscope, comprising: a pixel array being responsive to light energy received by the pixel array to produce pixel signals having a voltage level depending on the light energy received by the pixel array; a structured light source; a non-structured light source; one or more output circuits coupled to the pixel array to access the pixel signals produced by the pixel array; one or more analog-to-digital converters having a first dynamic range and a second dynamic range; one or more timing and control circuits, wherein said one or more timing and control circuits are coupled to the pixel array, said one or more output circuits, said one or more analog-to-digital converters, or a combination thereof, wherein said one or more timing and control circuits are arranged to: capture, by the pixel array, a structured-light image formed on a common image plane during a first frame period by applying first reset signals to the pixel array to reset rows of pixels of the pixel array, exposing the rows of pixels of the pixel array to first illumination from the structured light source to cause first analog signals from the rows of pixels and converting the first analog signals from the rows of pixels of the pixel array into first digital outputs for the structured-light image using one or more analog-to-digital converters; and capture, by the pixel array, a regular image formed on the common image plane during a second frame period longer than the first frame period by applying second reset signals to the pixel array to reset the rows of pixels of the pixel array, exposing the rows of pixels to second illumination from the non-structured light source to cause second analog signals from the rows of pixels, and converting the second analog signals from the rows of pixels into second digital outputs for the regular image using said one or more analog-to-digital converters; and wherein the structured-light image is captured before or after the regular image to derive depth or shape information for the regular image.","6.The endoscope of claim 5 further comprising a capsule housing adapted to be swallowed, wherein the pixel array, the structured light source, the non-structured light source, said one or more output circuits, and said one or more timing and control circuits are enclosed and sealed in the capsule housing.","7.The endoscope of claim 5, wherein said one or more analog-to-digital converters correspond to a configurable analog-to-digital converter to provide both the first dynamic range and the second dynamic range.","8.The endoscope of claim 5, wherein said one or more analog-to-digital converters correspond to two analog-to-digital converters with two different resolution to provide both the first dynamic range and the second dynamic range.","9.The endoscope of claim 5, wherein the structured-light image is captured at lower spatial resolution than the regular image.","10.A camera system, comprising: a pixel array being responsive to light energy received by the pixel array to produce pixel signals data having a voltage level depending on the light energy received by the pixel array; a structured light source; a non-structured light source; one or more output circuits coupled to the pixel array to access pixel signals produced by the pixel array; one or more analog-to-digital converters having a first dynamic range and a second dynamic range; one or more timing and control circuits coupled to the pixel array, said one or more output circuits, said one or more analog-to-digital converters, the structured light source, the non-structured light source, or a combination thereof, wherein said one or more timing and control circuits are configured to: capture, by the pixel array, a structured-light image formed on a common image plane during a first frame period by applying first reset signals to the pixel array to reset rows of pixels of the pixel array, exposing the rows of pixels of the pixel array to first illumination from the structured light source to cause first analog signals from the rows of pixels and converting the first analog signals from the rows of pixels of the pixel array into first digital outputs for the structured-light image using one or more analog-to-digital converters; and capture, by the pixel array, a first regular image formed on the common image plane during a second frame period by applying second reset signals to the pixel array to reset the rows of pixels of the pixel array, exposing the rows of pixels to second illumination from the non-structured light source to cause second analog signals from the rows of pixels, and converting the second analog signals from the rows of pixels into second digital outputs for the first regular image using said one or more analog-to-digital converters; and capture, by the pixel array, a second regular image formed on the common image plane during a third frame period by applying third reset signals to the pixel array to reset the rows of pixels of the pixel array, exposing the rows of pixels to the second illumination from the non-structured light source to cause third analog signals from the rows of pixels, and converting the third analog signals from the rows of pixels into third digital outputs for the second regular image using said one or more analog-to-digital converters; combine the second digital outputs and the third digital outputs to form a combined regular image; and wherein the structured-light image is captured between the first regular image and the second regular image to derive depth or shape information for the combined regular image, and the first frame period is shorter than a sum of the second frame period and the third frame period.","11.The camera system of claim 10, wherein the structured-light image is captured at lower spatial resolution than the first regular image and the second regular image.","12.The camera system of claim 10, wherein said one or more analog-to-digital converters correspond to a configurable analog-to-digital converter to provide both the first dynamic range and the second dynamic range.","13.The camera system of claim 10, wherein said one or more analog-to-digital converters correspond to two analog-to-digital converters with two different resolutions to provide both the first dynamic range and the second dynamic range.","14.An endoscope for in vivo viewing, comprising: a pixel array being responsive to light energy received by the pixel array to produce pixel signals having a voltage level depending on the light energy received by the pixel array; a structured light source; a non-structured light source; one or more output circuits coupled to the pixel array to access the pixel signals produced by the pixel array; one or more analog-to-digital converters having a first dynamic range and a second dynamic range; one or more timing and control circuits coupled to the pixel array, said one or more output circuits, said one or more analog-to-digital converters, the structured light source, the non-structured light source, or a combination thereof, wherein said one or more timing and control circuits are configured to: capture, by the pixel array, a structured-light image formed on a common image plane during a first frame period by applying first reset signals to the pixel array to reset rows of pixels of the pixel array, exposing the rows of pixels of the pixel array to first illumination from the structured light source to cause first analog signals from the rows of pixels and converting the first analog signals from the rows of pixels of the pixel array into first digital outputs for the structured-light image using one or more analog-to-digital converters; and capture, by the pixel array, a first regular image formed on the common image plane during a second frame period by applying second reset signals to the pixel array to reset the rows of pixels of the pixel array, exposing the rows of pixels to an ambient light or second illumination from the non-structured light source to cause second analog signals from the rows of pixels, and converting the second analog signals from the rows of pixels into second digital outputs for the first regular image using said one or more analog-to-digital converters; and capture, by the pixel array, a second regular image formed on the common image plane during a third frame period by applying third reset signals to the pixel array to reset the rows of pixels of the pixel array, exposing the rows of pixels to the ambient light or the second illumination from the non-structured light source to cause third analog signals from the rows of pixels, and converting the third analog signals from the rows of pixels into third digital outputs for the second regular image using said one or more analog-to-digital converters; combine the second digital outputs and the third digital outputs to form a combined regular image; and wherein the structured-light image is captured between the first regular image and the second regular image, and the first frame period is shorter than a sum of the second frame period and the third frame period.","15.The endoscope of claim 14, wherein the structured-light image is captured at lower spatial resolution than the first regular image and the second regular image.","16.The endoscope of claim 14, wherein said one or more analog-to-digital converters correspond to a configurable analog-to-digital converter to provide both the first dynamic range and the second dynamic range.","17.The endoscope of claim 14, wherein said one or more analog-to-digital converters correspond to two analog-to-digital converters with two different resolution to provide both the first dynamic range and the second dynamic range.","18.The endoscope of claim 14 further comprising a capsule housing adapted to be swallowed, wherein the pixel array, the structured light source, the non-structured light source, said one or more output circuits, and said one or more timing and control circuits are enclosed and sealed in the capsule housing."],[" BACKGROUND AND RELATED ART Devices for imaging body cavities or passages in vivo are known in the art and include endoscopes and autonomous encapsulated cameras.","Endoscopes are flexible or rigid tubes that pass into the body through an orifice or surgical opening, typically into the esophagus via the mouth or into the colon via the rectum.","An image is formed at the distal end using a lens and transmitted to the proximal end, outside the body, either by a lens-relay system or by a coherent fiber-optic bundle.","A conceptually similar instrument might record an image electronically at the distal end, for example using a CCD or CMOS array, and transfer the image data as an electrical signal to the proximal end through a cable.","Endoscopes allow a physician control over the field of view and are well-accepted diagnostic tools.","Capsule endoscope is an alternative in vivo endoscope developed in recent years.","For capsule endoscope, a camera is housed in a swallowable capsule, along with a radio transmitter for transmitting data, primarily comprising images recorded by the digital camera, to a base-station receiver or transceiver and data recorder outside the body.","The capsule may also include a radio receiver for receiving instructions or other data from a base-station transmitter.","Instead of radio-frequency transmission, lower-frequency electromagnetic signals may be used.","Power may be supplied inductively from an external inductor to an internal inductor within the capsule or from a battery within the capsule.","An autonomous capsule camera system with on-board data storage was disclosed in the U.S. Pat.","No.","7,983,458, entitled “In Vivo Autonomous Camera with On-Board Data Storage or Digital Wireless Transmission in Regulatory Approved Band,” granted on Jul.","19, 2011.The capsule camera with on-board storage archives the captured images in on-board non-volatile memory.","The capsule camera is retrieved upon its exiting from the human body.","The images stored in the non-volatile memory of the retrieved capsule camera are then accessed through an output port on in the capsule camera.","While the two-dimensional images captured by the endoscopes have been shown useful for diagnosis, it is desirable to be able to capture gastrointestinal (GI) tract images with depth information (i.e., three-dimensional (3D) images) to improve the accuracy of diagnosis or to ease the diagnosis process.","In the field of 3D imaging, 3D images may be captured using a regular camera for the texture information in the scene and a separate depth camera (e.g.","Time of Flight camera) for the depth information of the scene in the field of view.","The 3D images may also be captured using multiple cameras, where multiple cameras are often used in a planar configuration to capture a scene from different view angles.","Then, point correspondence is established among multiple views for 3D triangulation.","Nevertheless, these multi-camera systems may not be easily adapted to the GI tract environment, where the space is very limited.","In the past twenty years, a structured light technology has been developed to derive the depth or shape of objects in the scene using a single camera.","In the structured light system, a light source, often a projector is used to project known geometric pattern(s) onto objects in the scene.","A regular camera can be used to capture images with and without the projected patterns.","The images captured with the structured light can be used to derive the shapes associated with the objects in the scene.","The depth or shape information is then used with regular images, which are captured with non-structured floodlit light, to create 3D textured model of the objects.","The structured light technology has been well known in the field.","For example, in “ Structured - light 3 D surface imaging: a tutorial ” (Geng, in Advances in Optics and Photonics , Vol.","3, Issue 2, pp.","128-160, Mar.","31, 2011), structured light technology using various structured light patterns are described and the corresponding performances are compared.","In another example, various design, calibration and implement issues are described in “3-D Computer Vision Using Structured Light: Design, Calibration and Implementation Issues” (DePiero et al., Advances in Computers , Volume 43, Jan. 1, 1996, pages 243-278).","Accordingly, the details of the structured light technology are not repeated here.","While the structured light technology may be more suitable for 3D imaging of the GI tract than other technologies, there are still issues with the intended application for GI tract.","For example, most of the structured light applications are intended for stationary object.","Therefore, there is no object movement between the captured structured-light image and the regular image.","Nevertheless, in the capsule camera application for GI tract imaging, both the capsule camera and the GI parts (e.g.","small intestines and colons) may be moving.","Therefore, there will be relative movement between the structured-light image and the regular image if they are captured consecutively.","Furthermore, the capsule camera application is a very power-sensitive environment.","The use of structured light will consume system power in addition to capturing the regular images.","Besides, if one image with structured light is taken after each regular image, the useful frame rate will be dropped to half.","If the same frame rate of regular images is maintained, the system would have to capture images at twice the regular frame rate and consume twice the power in image capture.","Accordingly, it is desirable to develop technology for structured light application in the GI tract that can overcome these issues mentioned here."],[" BRIEF SUMMARY OF THE INVENTION An integrated image sensor for capturing a mixed structured-light image and regular image using an integrated image sensor are disclosed.","The integrated image sensor comprises a pixel array being responsive to light energy received by the pixel array to produce pixel signals having a voltage level depending on the light energy received by the pixel array; one or more output circuits coupled to the pixel array to access the pixel signals produced by the pixel array; one or more analog-to-digital converters having a first dynamic range and a second dynamic range; and one or more timing and control circuits coupled to the pixel array, said one or more output circuits, said one or more analog-to-digital converters, or a combination thereof.","The timing and control circuits are arranged to perform a set of actions including capturing a structured-light image formed on a common image plane during a first frame period by applying first reset signals to the pixel array to reset rows of pixels of the pixel array, exposing the rows of pixels of the pixel array to structured light to cause first analog signals from the rows of pixels, and converting the first analog signals from the rows of pixels of the pixel array into first digital outputs for the structured-light image using one or more analog-to-digital converters; and capturing, by the pixel array, a regular image formed on the common image plane during a second frame period longer than the first frame period by applying second reset signals to the pixel array to reset the rows of pixels of the pixel array, exposing the rows of pixels to non-structured light to cause second analog signals from the rows of pixels, and converting the second analog signals from the rows of pixels into second digital outputs for the regular image using said one or more analog-to-digital converters.","According to the present invention, the structured-light image is captured before or after the regular image to derive depth or shape information for the regular image.","In one embodiment, the analog-to-digital converters may correspond to a configurable analog-to-digital converter to provide both the first dynamic range and the second dynamic range.","In another embodiment, the analog-to-digital converters may correspond to two analog-to-digital converters with two different resolutions to provide both the first dynamic range and the second dynamic range.","In yet another embodiment, the timing and control circuits are further arranged to cause the structured-light image to be captured at lower spatial resolution than the regular image.","An endoscope based on the above integrated image sensor is also disclosed.","The endoscope further comprises a structured light source and a non-structured light source, which may be coupled to the timing and control circuits.","For capturing a structured-light image, the rows of pixels of the pixel array may be exposed to first illumination from the structured light source to cause first analog signals from the rows of pixels and the first analog signals from the rows of pixels of the pixel array are converted into first digital outputs for the structured-light image using one or more analog-to-digital converters.","For capturing a regular image formed on the common image plane, the rows of pixels may be exposed to second illumination from the non-structured light source to cause second analog signals from the rows of pixels, and the second analog signals from the rows of pixels are converted into second digital outputs for the regular image using said one or more analog-to-digital converters.","The endoscope may further comprises a capsule housing adapted to be swallowed, where the pixel array, the structured light source, the non-structured light source, said one or more output circuits, and said one or more timing and control circuits are enclosed and sealed in the capsule housing.","A camera system for capturing a structured-light image between two regular images is also disclosed.","The camera system comprises a pixel array, a structured light source, a non-structured light source, one or more output circuits, one or more analog-to-digital converters and one or more timing and control circuits.","A combined regular image is derived based on a first regular captured before the structured-light image and a second regular captured after the structured-light image.","Depth or shape information derived from the structured-light image is used for the combined regular image.","An endoscope based on the above camera system is disclosed.","The endoscope may further comprises a capsule housing adapted to be swallowed, where the pixel array, the structured light source, the non-structured light source, said one or more output circuits, and said one or more timing and control circuits are enclosed and sealed in the capsule housing."],["CROSS REFERENCES The present application is a divisional application of and claims the priority to U.S. Non-Provisional application Ser.","No.","14/884,788, filed on Oct. 16, 2015.The U.S. Non-Provisional application is incorporated by reference in its entirety.","FIELD OF THE INVENTION The present invention relates to a single image sensor capable of capturing structured-light images and regular image, where the structured-light image is used to derive depth or shape information related to the corresponding regular image.","BACKGROUND AND RELATED ART Devices for imaging body cavities or passages in vivo are known in the art and include endoscopes and autonomous encapsulated cameras.","Endoscopes are flexible or rigid tubes that pass into the body through an orifice or surgical opening, typically into the esophagus via the mouth or into the colon via the rectum.","An image is formed at the distal end using a lens and transmitted to the proximal end, outside the body, either by a lens-relay system or by a coherent fiber-optic bundle.","A conceptually similar instrument might record an image electronically at the distal end, for example using a CCD or CMOS array, and transfer the image data as an electrical signal to the proximal end through a cable.","Endoscopes allow a physician control over the field of view and are well-accepted diagnostic tools.","Capsule endoscope is an alternative in vivo endoscope developed in recent years.","For capsule endoscope, a camera is housed in a swallowable capsule, along with a radio transmitter for transmitting data, primarily comprising images recorded by the digital camera, to a base-station receiver or transceiver and data recorder outside the body.","The capsule may also include a radio receiver for receiving instructions or other data from a base-station transmitter.","Instead of radio-frequency transmission, lower-frequency electromagnetic signals may be used.","Power may be supplied inductively from an external inductor to an internal inductor within the capsule or from a battery within the capsule.","An autonomous capsule camera system with on-board data storage was disclosed in the U.S. Pat.","No.","7,983,458, entitled “In Vivo Autonomous Camera with On-Board Data Storage or Digital Wireless Transmission in Regulatory Approved Band,” granted on Jul.","19, 2011.The capsule camera with on-board storage archives the captured images in on-board non-volatile memory.","The capsule camera is retrieved upon its exiting from the human body.","The images stored in the non-volatile memory of the retrieved capsule camera are then accessed through an output port on in the capsule camera.","While the two-dimensional images captured by the endoscopes have been shown useful for diagnosis, it is desirable to be able to capture gastrointestinal (GI) tract images with depth information (i.e., three-dimensional (3D) images) to improve the accuracy of diagnosis or to ease the diagnosis process.","In the field of 3D imaging, 3D images may be captured using a regular camera for the texture information in the scene and a separate depth camera (e.g.","Time of Flight camera) for the depth information of the scene in the field of view.","The 3D images may also be captured using multiple cameras, where multiple cameras are often used in a planar configuration to capture a scene from different view angles.","Then, point correspondence is established among multiple views for 3D triangulation.","Nevertheless, these multi-camera systems may not be easily adapted to the GI tract environment, where the space is very limited.","In the past twenty years, a structured light technology has been developed to derive the depth or shape of objects in the scene using a single camera.","In the structured light system, a light source, often a projector is used to project known geometric pattern(s) onto objects in the scene.","A regular camera can be used to capture images with and without the projected patterns.","The images captured with the structured light can be used to derive the shapes associated with the objects in the scene.","The depth or shape information is then used with regular images, which are captured with non-structured floodlit light, to create 3D textured model of the objects.","The structured light technology has been well known in the field.","For example, in “Structured-light 3D surface imaging: a tutorial” (Geng, in Advances in Optics and Photonics, Vol.","3, Issue 2, pp.","128-160, Mar.","31, 2011), structured light technology using various structured light patterns are described and the corresponding performances are compared.","In another example, various design, calibration and implement issues are described in “3-D Computer Vision Using Structured Light: Design, Calibration and Implementation Issues” (DePiero et al., Advances in Computers, Volume 43, Jan. 1, 1996, pages 243-278).","Accordingly, the details of the structured light technology are not repeated here.","While the structured light technology may be more suitable for 3D imaging of the GI tract than other technologies, there are still issues with the intended application for GI tract.","For example, most of the structured light applications are intended for stationary object.","Therefore, there is no object movement between the captured structured-light image and the regular image.","Nevertheless, in the capsule camera application for GI tract imaging, both the capsule camera and the GI parts (e.g.","small intestines and colons) may be moving.","Therefore, there will be relative movement between the structured-light image and the regular image if they are captured consecutively.","Furthermore, the capsule camera application is a very power-sensitive environment.","The use of structured light will consume system power in addition to capturing the regular images.","Besides, if one image with structured light is taken after each regular image, the useful frame rate will be dropped to half.","If the same frame rate of regular images is maintained, the system would have to capture images at twice the regular frame rate and consume twice the power in image capture.","Accordingly, it is desirable to develop technology for structured light application in the GI tract that can overcome these issues mentioned here.","BRIEF SUMMARY OF THE INVENTION An integrated image sensor for capturing a mixed structured-light image and regular image using an integrated image sensor are disclosed.","The integrated image sensor comprises a pixel array being responsive to light energy received by the pixel array to produce pixel signals having a voltage level depending on the light energy received by the pixel array; one or more output circuits coupled to the pixel array to access the pixel signals produced by the pixel array; one or more analog-to-digital converters having a first dynamic range and a second dynamic range; and one or more timing and control circuits coupled to the pixel array, said one or more output circuits, said one or more analog-to-digital converters, or a combination thereof.","The timing and control circuits are arranged to perform a set of actions including capturing a structured-light image formed on a common image plane during a first frame period by applying first reset signals to the pixel array to reset rows of pixels of the pixel array, exposing the rows of pixels of the pixel array to structured light to cause first analog signals from the rows of pixels, and converting the first analog signals from the rows of pixels of the pixel array into first digital outputs for the structured-light image using one or more analog-to-digital converters; and capturing, by the pixel array, a regular image formed on the common image plane during a second frame period longer than the first frame period by applying second reset signals to the pixel array to reset the rows of pixels of the pixel array, exposing the rows of pixels to non-structured light to cause second analog signals from the rows of pixels, and converting the second analog signals from the rows of pixels into second digital outputs for the regular image using said one or more analog-to-digital converters.","According to the present invention, the structured-light image is captured before or after the regular image to derive depth or shape information for the regular image.","In one embodiment, the analog-to-digital converters may correspond to a configurable analog-to-digital converter to provide both the first dynamic range and the second dynamic range.","In another embodiment, the analog-to-digital converters may correspond to two analog-to-digital converters with two different resolutions to provide both the first dynamic range and the second dynamic range.","In yet another embodiment, the timing and control circuits are further arranged to cause the structured-light image to be captured at lower spatial resolution than the regular image.","An endoscope based on the above integrated image sensor is also disclosed.","The endoscope further comprises a structured light source and a non-structured light source, which may be coupled to the timing and control circuits.","For capturing a structured-light image, the rows of pixels of the pixel array may be exposed to first illumination from the structured light source to cause first analog signals from the rows of pixels and the first analog signals from the rows of pixels of the pixel array are converted into first digital outputs for the structured-light image using one or more analog-to-digital converters.","For capturing a regular image formed on the common image plane, the rows of pixels may be exposed to second illumination from the non-structured light source to cause second analog signals from the rows of pixels, and the second analog signals from the rows of pixels are converted into second digital outputs for the regular image using said one or more analog-to-digital converters.","The endoscope may further comprises a capsule housing adapted to be swallowed, where the pixel array, the structured light source, the non-structured light source, said one or more output circuits, and said one or more timing and control circuits are enclosed and sealed in the capsule housing.","A camera system for capturing a structured-light image between two regular images is also disclosed.","The camera system comprises a pixel array, a structured light source, a non-structured light source, one or more output circuits, one or more analog-to-digital converters and one or more timing and control circuits.","A combined regular image is derived based on a first regular captured before the structured-light image and a second regular captured after the structured-light image.","Depth or shape information derived from the structured-light image is used for the combined regular image.","An endoscope based on the above camera system is disclosed.","The endoscope may further comprises a capsule housing adapted to be swallowed, where the pixel array, the structured light source, the non-structured light source, said one or more output circuits, and said one or more timing and control circuits are enclosed and sealed in the capsule housing.","BRIEF DESCRIPTION OF THE DRAWINGS FIG.","1 illustrates exemplary analog-to-digital converter with 8-bit dynamic range.","FIGS.","2A-B illustrate ramp voltage waveforms used as a reference signal for the analog-to-digital converter, where the waveforms shown are for 9-bit (FIG.","2A) and 6-bit (FIG.","2B) dynamic resolutions.","FIG.","3 illustrates an exemplary block diagram of a pixel array for capturing a tandem structured-light image and regular image according to an embodiment of the present invention.","FIG.","4A illustrates an exemplary timing chart for capturing two regular images.","FIG.","4B illustrates an example of a tandem structured-light image and regular image according to an embodiment of the present invention.","FIG.","5 illustrates an exemplary timing corresponding to FIG.","4B for applying the structured light for capturing a structured-light image according to an embodiment of the present invention, where the structured light duration is explicitly shown and some notations are deleted for clear illustration.","FIG.","6 illustrates another view of applying the structured light for capturing a structured-light image and capturing a regular image according to an embodiment of the present invention.","FIG.","7A illustrates exemplary timing charts for capturing a two-session image according to an embodiment of the present invention, where a first regular sub-image is captured in the first session and a mixed image consisting of a structured-light image and a second regular sub-image is captured in the second session, the regular image are combined as the final output and the integration period for the first session is approximately the same as the integration period for the second session.","FIG.","7B illustrates exemplary timing charts similar to these of FIG.","7A, where the integration period for the first session is approximately three times as long as the integration period for the second session.","FIG.","8 illustrates an exemplary flowchart for capturing a tandem structured-light image and regular image according to an embodiment of the present invention, where the structured-light image has lower dynamic range than the regular image.","FIG.","9 illustrates an exemplary flowchart for capturing a tandem structured-light image and regular image according to another embodiment of the present invention, where the structured-light image has lower dynamic range than the regular image.","DETAILED DESCRIPTION OF THE INVENTION It will be readily understood that the components of the present invention, as generally described and illustrated in the figures herein, may be arranged and designed in a wide variety of different configurations.","Thus, the following more detailed description of the embodiments of the systems and methods of the present invention, as represented in the figures, is not intended to limit the scope of the invention, as claimed, but is merely representative of selected embodiments of the invention.","References throughout this specification to “one embodiment,” “an embodiment,” or similar language mean that a particular feature, structure, or characteristic described in connection with the embodiment may be included in at least one embodiment of the present invention.","Thus, appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment.","Furthermore, the described features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.","One skilled in the relevant art will recognize, however, that the invention can be practiced without one or more of the specific details, or with other methods, components, etc.","In other instances, well-known structures, or operations are not shown or described in detail to avoid obscuring aspects of the invention.","The illustrated embodiments of the invention will be best understood by reference to the drawings, wherein like parts are designated by like numerals throughout.","The following description is intended only by way of example, and simply illustrates certain selected embodiments of apparatus and methods that are consistent with the invention as claimed herein.","Endoscopes are normally inserted into the human body through a natural opening such as the mouth or anus.","Therefore, endoscopes are preferred to be small sizes so as to be minimally invasive.","To derive or capture the depth or shape information while capturing live images or videos of the GI tract with endoscopes, it is crucial to maintain the small-size form factor.","Besides, with the small size and the capability to capture depth information along with corresponding images or video, such camera also finds its applications in other applications requiring compact size, such as a wearable devices.","One technique that may capture depth information is to use a color filter placed on top of selected sensor pixels with the passband reasonably narrow and capture the color information and depth information simultaneously.","The environment light sources with spectrum in the filter passband will cause negligible amount of energy projected onto the sensor.","For the case of RGB pixels, a fourth type of pixels may be added to capture light with the spectrum in the passband of the filter placed on top of these pixels.","Then, the structured light that has the spectrum substantially in the passband can be projected onto the scene.","However this approach will reduce the spatial resolution of the images or video captured using such image sensor.","Another technique is to obtain the depth information as well as 3D topology by projecting structured light patterns that are visible in the RGB sensors.","However the real time image and/or video will be confounded by the structured light superimposed on it.","This invention describes methods to use a single camera to achieve depth information by using the structured light approach while taking images or real time video using the camera.","As mentioned before, a conventional structured light approach with a single camera would incur several drawbacks.","For example, the camera with a frame rate of 30 frames per second may be used.","A conventional approach would take live video with interleaved images corresponding to images with and without the structured light.","One issue is that the depth information is 1/30 second away from corresponding images to be viewed.","If there is any movement in the scene, the depth information may not accurately represent the 3D topology of the corresponding images at 1/30 second away.","In addition, the effective frame rate for the video to be viewed is dropped to 15 frames per second in this example.","In some video applications, the frame rate is crucial for the intended application.","For example, a high frame-rate camera with frame rate in the 100's per second or more is required to capture video of fast moving objects such as a travelling bullet.","In this case, the use of structured light would cut the frame rate to half and may hinder the intended application.","For a capsule camera, the video for the gastrointestinal (GI) tract is normally a few frames per second and the camera could be operating at twice the original frame rate to compensate the reduction of effective frame rate due to capturing structured-light images.","However, it would result in twice as much power consumption, which is not desirable in the power-limited capsule environment.","Each frame rate has a corresponding frame period.","During the frame period, the sensor will spend a subset of the frame period for accumulating charges emitted in response to incidental light on the sensor.","The integration time must be sufficiently small so that the image is substantially stationary to avoid causing any motion blur in the captured image.","FIG.","1 illustrates an example of ADC (analog-to-digital converter) that can be used for an image sensor.","The ADC includes a comparator (110) to compare an input analog signal (120) with a reference signal (130).","The analog signal (120) from the analog circuits connected to a pixel is coupled to one terminal of the comparator to compare with a ramp voltage.","In one embodiment, the ramp voltage can be generated using a clock that is used for digital logic circuits so that the ramp voltage goes one step higher according to each driving clock.","FIG.","2A and FIG.","2B show two examples of ramp voltage corresponding to 9-bit (i.e., 512 levels) and 6-bit (i.e., 64 levels) respectively.","The same clock supplied to generate the ramp voltage is also counted by the counter (140).","When the ramp voltage level reaches the analog signal (120) from the pixel analog readout circuits connected to a pixel, the comparator output will switch (e.g.","from high to low or low to high) to indicate the event.","At the same time, the comparator output signal will trigger the registers (150) so as to latch a counter value that counts the number of clocks indicating the ramp voltage value crossing the analog signal (120).","The output from the pixel is often measured twice using the correlated double sampling (CDS) technique, which is well known in the field to take care of the fixed pattern noise due to manufacturing variation among pixels.","The offset reset signal can be removed using analog circuits (e. g. correlated double sampling) or digital circuits.","For digital implementation, the digital counter readout after reset can be subtracted from the digital counter readout of a pixel after an integration period.","There are several factors determining how fast the pixel can accumulate electronic charges and how fast the signal can be readout.","As shown in the example of FIG.","1, the analog output signal (120) from analog circuits connected to each pixel is compared to a reference signal (i.e., the voltage ramp).","Depending on the desired digital pixel resolution (e.g.","9 bits vs 6 bits), a corresponding ramp signal can be generated.","The readout speed will depend on the speed of the counter, the comparator and other related circuits.","The ramp signal corresponding to higher digital resolution (i.e., higher dynamic range) will take longer time to generate.","The implementation to support 6-bit digital dynamic range as shown in FIG.","2B will be 8 times faster than the implementation for digital 9-bit dynamic range as shown in FIG.","2A.","There are other variations to implement ADC, such as successive approximation ADC.","For the successive approximation ADC, the reference voltage starts with a coarse level.","Depending on whether the input voltage is higher or lower than the reference voltage, the reference voltage is refined by increasing or decreasing the previous reference voltage by half of a previous voltage interval.","The refined reference voltage is used as a current reference voltage for next successive comparison.","The process is terminated until a desired resolution is achieved.","In each round of successive approximation, one bit is used to indicate whether the input voltage is higher or lower than the reference voltage.","Accordingly, the ADC resolution corresponds to the number of successive approximation of the successive-approximation ADC.","In general, the higher the dynamic ranges, the longer the readout will be.","Not only more comparisons will be required, but also the voltage will take longer time to settle down since the accuracy requirements of the ramp up voltage or reference voltages are high.","The sensor array has a large intrinsic RC constant, which takes time to settle to within the limits required by the accuracy.","In the case of a high dynamic range, the conductor line carrying the reference voltage (i.e., the ramp reference signal) requires more time to settle due to the inductance, along with R (resistance) and C (capacitance), of the conductor line.","The length of the conductor line for the sensor array usually is in the order of 1,000's μm (micro meter), which may result in an inductance around a few nH (nano Henry).","Unlike resistance, the inductance will not be scaled down inversely proportional to the conductor cross section.","The high dynamical range is an important factor for image/video quality to provide detailed shades of the objects in the scene.","On the other hand, the images for structured light pattern are mainly used to derive depth/shape information based on the geometric information of know patterns, such as grids.","The important information to be derived is related to the locations of the grid lines.","Accordingly, the requirement on the dynamic range is substantially lower than that for the regular images to be viewed by the human eyes.","Since the required dynamic range for the structured-light image is much less than that for a regular image, the present invention takes advantage of the different dynamic range requirements to shorten the frame period for the structured-light image.","FIG.","3 illustrates a simplified system block diagram of an integrated image sensor incorporating an embodiment of the present invention.","The integrated image sensor comprises a pixel array (310) being responsive to light energy received by the pixel array to produce signal data having a voltage level depending on the light energy received, output circuits (320) coupled to the pixel array to access the signal data produced by the pixel array, one or more analog-to-digital converters (ADCs, 330) having a first dynamic range and a second dynamic range, and timing/control circuits (340a and 340b).","The pixel array may consist of monochrome pixels or color pixels.","The pixel array can be based on the CMOS technology or the CCD technology.","The output circuits are coupled to the pixel array under the control of the timing/control circuits.","For example, the pixel array outputs can be transferred to the output circuits row by row under the control of the timing/control circuits.","The output circuits may also include amplifier and CDS circuit, where the CDS circuit is used to take care of the offset in individual pixels after reset.","While the timing/control circuits (340a and 340b) are shown as two separate blocks, they may also be implemented as a unified block.","The ADC circuit(s) is capable of operating at a first dynamic range and a second dynamic range.","The first dynamic range is smaller than the second dynamic range.","For example, the first dynamic range may correspond to 6 bits and the second dynamic range may correspond to 9 bits.","Individual ADCs with different dynamic ranges may be used.","Since the structured-light image and the regular image are captured in serial instead of parallel, a single ADC with configurable dynamic range may also be used.","For example, an adaptively configurable ADC is disclosed in U.S. Pat.","No.","8,369,458 issued to Wong et al.","on Feb. 5, 2013.The timing/control circuits may include row scan circuit and column scan circuit.","The timing/control circuits are also responsible to generate various control signals such as reset signals.","In the following, preferred embodiments are provided regarding configuring the image sensor to capture structured-light images and regular images.","FIG.","4A illustrates an example of the timing for a regular image sensor, where the row timing is shown from frame to frame in the horizontal direction and from the first row (top) to the last row (bottom) in the vertical direction.","In a typical image sensor, the image pixels are read out row by row.","There are several phases of operation for each row including row reset, integration and readout.","The operations usually are staggered from row to row as shown in FIG.","4A.","However, the readout operation for a current row has to wait until the previous row readout is complete.","For a regular image sensor, the similar timing patterns just repeat from frame to frame with the same frame time.","The period time is the same for all frames.","FIG.","4A illustrates the general timing diagram for a typical image sensor.","The timing charts may not be drawn to scale.","FIG.","4B illustrates an example of the timing for capturing a mixed structured-light image and regular image according to one embodiment of the present invention, where the structured light is taken with smaller dynamic range.","The frame duration for the structured-light image is much shorter than the frame duration of the following regular image as illustrated in FIG.","4B.","The timing charts in FIG.","4B are not drawn to scale, particularly for the structured light section.","The section for the structured light has been expanded in order to illustrate more details.","In FIG.","4B, the timing signals associated with the structured-light image are shown in Bold-Italic font.","The less dynamic range can be achieved, for example, by fewer comparisons with the reference voltage generated by ramping up voltage with a larger step as illustrated in FIGS.","2A and 2B.","Alternatively, the reference voltage can be generated with a smaller ramp range between the starting voltage and the ending voltage.","Since the readout is faster for this structured-light image than the regular image, the structured-light image could be squeezed within the reset timing period of the regular image.","Since the structure light image does not need a dynamic range as high as the regular image, the structure light image reset does not need to be as thorough as that for regular image.","Therefore, a shorter reset time could be used for the structured light.","Accordingly, in one embodiment, the minimum row reset time among the rows of pixels of the image sensor for the structured-light image can be substantially shorter than the minimum row reset time among the rows of pixels of the image sensor for the regular image.","FIG.","5 is identical to FIG.","4B with some notations eliminated to conveniently demonstrate the timing setup.","The duration for the structured light is indicated.","The structured light duration could be substantially close to the end of first row integration phase for the structured light.","On the other hand, the structured light duration must be within the integration phase of the last row for the structured-light image.","The optimal structure light pulse duration is from the start of last row integration to the start of first row readout.","In order to speed up the operation of capturing a structured-light image, as well as to reduce the impact of the energy of the other light sources, such as ambient light, in the scene entering the camera, the structured light duration is set to be very short.","If the integration requires a longer time than desired, the structural light pulse energy can be increased by increasing either the intensity or the duration.","In a preferred embodiment, the structured light intensity is substantially stronger compared with the light intensity from the regular light source or ambient light.","However, the structured light can be applied for a substantially shorter period than the human visual retention time, making the image of the scene exposed by non-structured light relatively weaker and the signal/noise ratio much stronger for the structure light.","The non-structured light may correspond to a broadband, narrowband, or fluoroscopic light.","The energy of the structure light pulse may be limited by system power constraints or by a desire not to annoy, distract, or eye-damage persons in the scene exposed to the structured light.","Another energy limitation may be a tissue-damage optical-energy threshold in medical-imaging applications.","The sensor analog gain may be increased so that the pixel luminance resulting from structured light illumination is well above background noise and luminance from other light sources while the structured light energy is at an acceptably low level.","Increased gain results in greater noise amplification and reduced sensor dynamic range.","While the main intended application is for the GI tract, the usage of short-duration and high-intensity structured light can also benefit the non-GI applications.","For example, the present invention may also be applied to conventional photography to capture mixed regular images and structured-light images of natural scenes and use the depth or shape information derived from the structured images to render 3D images of the scene.","In order to derive more reliable depth or shape information using the structured-light images, it is desirable to select a structured-light source having light spectrum very different from the color spectrum of the underlying scene captured under ambient light or illuminated by one or more non-structured lights.","While there are readout schemes that may start to read the higher (i.e., most significant) bits during integration, the readout with a larger dynamic range will take a longer time to complete the readout.","This is due to more comparisons and longer reference voltage settling time needed.","Accordingly, reducing the dynamic range for the structured-light image will be able to reduce the row processing duration.","This is also true for image sensors operated in the global shutter mode.","Accordingly, the settling time associated with a reference voltage, provided to the analog-to-digital converters to compare with an input analog voltage, is shorter for the first structured-light image than for the regular image.","Due to the less accuracy required, the reset signal does not need to be held for so long to reset the pixels and/or related circuits to an optimal level.","As shown in FIG.","5, the structured light is preferred to be applied at a specific time so that the duration is short, but the short duration covers at least a portion of integration time for all pixel rows.","The control signal to trigger the structured light may be derived from the frame signal and the clock.","However, the control signal for the structured light may also come from other module of the integrated sensor.","In another implementation, a fixed or programmable delay for the control signal from the sensor can be used to adjust the timings to match optimal system design.","In one embodiment, the structured light is generated using multiple light sources with at least two different colors or patterns.","By using multiple colors, a color or a combination of colors can be selected to cause the light spectrum of the selected color(s) substantially different from the color spectrum of associated with regular images of an anticipated scene illuminated by the non-structured light or under ambient light.","The spectrum associated with the structured light can be substantially distinct from the spectrum associated with regular images of an anticipated scene.","The image sensor may correspond to a color image sensor comprising at least first and second color pixels arranged in a mosaic pattern, and the spectrum associated with the structured light can be substantially concentrated on the spectrum of first or second color pixels.","The structured-light image can be captured at reduced spatial resolution by reading out only selected digital outputs related to the first or second pixels having spectrum substantially corresponding to the structured-light spectrum.","For capsule applications, the integrated image sensor may be inside a sealed capsule housing for imaging gastrointestinal tract of human body.","Since there is no ambient light in the GI tract, the capsule device has to provide both the structured light and the lighting for regular images.","In this case, the structured light sources for structured light images and the illumination light sources for regular images can be sealed in the housing.","FIG.","6 illustrates another perspective of the timing charts corresponding to these in FIG.","5, where the image readouts for the structured image and regular images are highlighted using different fill-patterns.","The timing signals related to the structured-light image are indicated in FIG.","6, where sli-reset corresponds to the structured-light image reset, sli-integration corresponds to the structured-light image integration and sli-readout corresponds to the structured-light image readout.","The structured light duration is also indicated in FIG.","6, where the structured light is applied during the sli-integration.","The whole period for capturing the structured-light image may occur during the reset period of a regular image reset.","In the example shown in FIG.","6, the reset for the structure light image may be very brief compared to the reset period for a regular image.","The timing charts in FIG.","6 illustrate the cycles for capturing a tandem structured-light image and regular image, where the timing for the regular image is modified.","In particular, the reset period of the regular image capture is substantially reduced to accommodate the capture of the structured-light image.","Accordingly, the timing charts incorporating an embodiment of the present invention shown in FIG.","6 can be considered as two separate images or a combo of structured-light image and timing-modified regular image.","In the embodiments disclosed above, a structured light image is captured temporally close to a regular image so as to provide more accurate depth/shape information for the associated regular image.","In another embodiment, a two-session capture is disclosed, where the regular image is split into two sub-images with a structured light image captured in between.","The regular integration time for the regular image is split between the two sub-images.","The digital outputs for the two regular sub-images are combined to form a regular image output.","This approach has several advantages.","First, each sub-image is converted into digital outputs using the ADC that is used for the regular image.","Accordingly, each sub-image will have the same dynamic range as the regular image of a one-session approach.","When the digital outputs of the two sub-images are combined, the final regular image still preserves the full dynamic range.","Assume that a pixel with full integration time would get an analog signal to be digitized into 128.By using half the integration time for each session, the pixel will get half the analog signal amount and thus will be digitized to 64.The half integration time is important because integration time may be a substantial component in the total period.","Therefore, by using only half the integration time for each session will cause the total time shorter than otherwise.","FIG.","7A illustrates an example of two-session approach according to an embodiment of the present invention.","In the first session, a regular image can be captured using regular timing.","In the second session, a mixed image is captured, which includes a structured-light image and a timing-modified regular image.","The structured-light image is captured between the two session readouts.","The first session readout may be temporally stored in a memory or buffer inside the image sensor or outside.","When the second session readout is complete, the two readout values from two sessions are combined together.","Since the structured-light image is captured between the two sub-images of a regular-scene image, the structured-light image should be very close to the captured regular-scene images temporally.","Accordingly, the structured-light image should closely correlate to the regular scene image.","The readouts from two sub-images associated with the two sessions are combined into one regular image.","In one embodiment, a group of interleaved sub-regular images and structured-light images are taken consecutively.","For example, the images in odd numbers are for regular images and images in even numbers are for structured-light images.","Images 1 and 3, which are two sub-images, could be combined to form a combined regular image corresponding to image 2, which is a structured-light image.","Similarly, images 3 and 5, which are two sub-images, could be combined to form a combined regular image corresponding to image 4, which is a structured-light image.","Images 5 and 7 could be combined to form a combined regular image corresponding to image 6, which is a structured-light image.","The process can continue with each regular sub-image used twice in general.","In this case, the weighting factors for images 1, 3, 5, 7, .",".",".","could be 50/50/50/50 .",".",".",", or it could be 60/40/60/40/60 .",".",".","with the principle of the two combined weighting is 100 percent of the targeted integration time.","In FIG.","7A, the integration time for the two sub-images is roughly the same.","However, the two integration time may also be different.","For example, the integration time for the first sub-image may be three times as long as the integration time (also called integration period in this disclosure) for the second sub-image as shown in FIG.","7B.","In this case, when the digital outputs from the two sub-images are combined, the combined image has the effect of weighted sum of the first sub-image (i.e., ¾) and the second sub-image (¼).","There is no need to perform the weighted sum associated with different integration periods since the weighting will be reflected in the charges accumulated during respective integration periods.","The longer integration period results in more accumulated charges, which result in a higher analog signal.","Accordingly, the sum of the two digital readouts represents the weighted sum of the two sub-images, where the weighting factors correspond to the integration periods.","In another application of structured-light images, multiple structured light images are used to derive more 3D points than a single structured-light image for one or more associated regular images.","For example, multiple structured-light images may be captured consecutively by a capsule camera while traversing in the human gastrointestinal (GI) tract.","The regular image can be captured between, before or after the multiple structured-light images.","The captured structured-light images can be used to derive a 3D model of the GI tract.","This 3D GI tract model can be useful for examining associated regular images of the GI tract.","For two-session regular image capturing with intervening structured-light image, the means for reducing the frame period for the structured-light image as mentioned before can be used.","For example, the structured-light image can be captured with a reduced dynamic range of the image sensor compared to the first regular image and the second regular image.","The structured-light image may also be captured at lower spatial resolution than the first regular image and the second regular image.","Furthermore, the structured-light image can be captured with a reduced image area in a vertical direction, horizontal direction or both compared to the first regular image and the second regular image.","In some cases, the depth or shape information is of interest only for a selected image area.","In these cases, the structured-light image can be captured for the selected image area only.","Accordingly, it serves an alternative means to reduce the frame period of the structured-light image.","The reduced image area may correspond to a reduced image area in the vertical direction, horizontal direction or both compared to the regular image.","The means may also be combined with other means, such as reducing the dynamic range or reducing the spatial resolution, for reducing the frame period of the structured-light image.","Reducing the spatial resolution by itself can be used as a technique to reduce the frame period for the structured-light images.","For example, the structured-light image can be captured with reduced vertical resolution by only retaining selected rows of pixels and skipping remaining rows of pixels of the image sensor.","For an endoscope application, including a capsule endoscope application, there is no ambient light and the lighting from the endoscope is the only light source.","Therefore, the integration time of each row needs not to be the same as long as the duration of the light exposure is the same for every line.","For the endoscope environment, the lower dynamic range of structured-light image than that of the regular image also benefits from temporal proximity between the structured-light image and the regular image.","Therefore, the structured-light image according to the present invention should bear more accurate depth or shape information correlated with the regular image.","For power sensitive applications such as the capsule endoscope and wearable device, less dynamic range also saves power due to less comparison operations and shorter integration time, which requires less structured light energy.","On the other hand, since signal to noise ratio is not so important to structured-light image, its gain can be set to substantial higher to further save energy.","A camera system usually includes an exposure control function to control the operating parameters of the image sensor so that the overall intensity of the image taken is at the right level within certain range conducive for viewing.","The image intensity is derived from the pixel intensity.","The detailed control often is subject to the preference of camera system designer.","For example, the image intensity is determined by the average of pixel intensity of central portions of the image.","In another example, the mean of the pixel intensity of the central portion is used as the image intensity.","In another example, multiple areas of the image are used instead of the central portion.","If the intensity is found to be too high, then the gain or the integration time can be reduced.","If the intensity is too low then the gain or the integration time can be increased.","Furthermore, the amount of adjustment from one image to the next can be dependent on how much the intensity is deviated from the preferred level or range.","A camera system may also provide the lighting to augment the ambient light.","The lighting from the camera system may also be the sole lighting source, such as a regular endoscope or a capsule endoscope.","For a camera used for pipe examination or for deep sea exploration, the lighting from the camera is also the sole lighting source.","In such a system, the exposure control will control the gain, integration time, lighting intensity and/or energy or a combination of them.","If an image has too strong intensity, the value of (gain×integration×light energy) will be reduced for the subsequent image or images.","On the other hand, if an image has too weak intensity, the value of (gain×integration×light energy) will be increased for the subsequent image or images.","The amount of adjustment from one image to the next may dependent on much the intensity is deviated from the preferred level or range.","An embodiment of the present invention addresses dual exposure controls for capturing structured-light images and regular images using a single image sensor.","Based on this embodiment, there are two exposure control loops for the same image sensor, one for the structured-light image and the other for the regular image.","In the case that the regular image lighting is substantially dependent on the light controlled by the camera system (e.g.","negligible or no ambient light), the exposure condition is very similar for both structured light and the regular light since the distance to the scene is practically the same for both cases.","Accordingly, one exposure control loop could be used and the other exposure control is dependent on the first exposure control loop.","For example, (gain×integration×light energy) of structure light can be linearly dependent on (gain×integration×light energy) of regular light image or vice versa.","In another embodiment, other dependence is used.","For example, gamma-type dependence or dependence on the intensity distribution may also be used.","In the case where there is ambient light, the structured-light needs to be sufficiently strong to cause the structure light pattern more discernable in the structured-light image for analysis.","In this case, the light intensity in the above analysis is composed of ambient light and light or lights projected to the scene controlled by the exposure control of the camera system.","In this case, there might be no need for camera control to project light for regular image if ambient light is sufficient.","However the structured light has another constraint that the projected structured-light must be strong enough to show its pattern and/or color in the structured-light image.","If the spectrum of the structured light is substantially concentrated in the spectrum of one particular color of the image sensor, the intensity of that particular color of the structured light image and/or the overall intensity are considered.","In one embodiment, if structured-light sources are capable of generating multiple colors, then the intensity of each color component in the regular image is considered.","The structured light source color corresponding to the weaker color in the regular image is chosen in order to make the structured color stand out or to have a higher signal to background ratio statistically for easy analysis FIG.","8 illustrates an exemplary flowchart for capturing a mixed structured-light image and regular image according to an embodiment of the present invention.","Capturing a first structured-light image using the image sensor during a first frame period in step 810.A regular image is captured using the image sensor during a second frame period, where the first frame period is shorter than the second frame period and the first structured-light image is captured before or after the regular image in step 820.FIG.","9 illustrates an exemplary flowchart for capturing a tandem structured-light image and regular image according to one embodiment of the present invention, where the structured-light image has lower dynamic range than the regular image.","First reset signals are applied to a pixel array to reset rows of pixels of the pixel array in step 910.The rows of pixels of the image sensor are exposed to structured light to cause first analog signals from the rows of pixels in step 920.The first analog signals from the rows of pixels of the image sensor are converted into first digital outputs for the first structured-light image using one or more analog-to-digital converters in step 930.Second reset signals are applied to the pixel array to reset the rows of pixels of the pixel array in step 940.The rows of pixels are exposed to non-structured light to cause second analog signals from the rows of pixels in step 950.The second analog signals from the rows of pixels are converted into second digital outputs for the regular image using said one or more analog-to-digital converters in step 960.The first structured-light image is captured before or after the regular image in step 960, where the first dynamic range is smaller than the second dynamic range.","The invention may be embodied in other specific forms without departing from its spirit or essential characteristics.","The described examples are to be considered in all respects only as illustrative and not restrictive.","Therefore, the scope of the invention is indicated by the appended claims rather than by the foregoing description.","All changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope."]],"string":"[\n [\n \"Single Image Sensor for Capturing Mixed Structured-light Images and Regular Images\",\n \"An integrated image sensor for capturing a mixed structured-light image and regular image using an integrated image sensor are disclosed.\",\n \"The integrated image sensor comprises a pixel array, one or more output circuits, one or more analog-to-digital converters, and one or more timing and control circuits.\",\n \"The timing and control circuits are arranged to perform a set of actions including capturing a regular image and a structured-light image.\",\n \"According to the present invention, the structured-light image captured before or after the regular image is used to derive depth or shape information for the regular image.\",\n \"An endoscope based on the above integrated image sensor is also disclosed.\",\n \"The endoscope may comprises a capsule housing adapted to be swallowed, where the components of integrated image sensor, a structured light source and a non-structured light source are enclosed and sealed in the capsule housing.\"\n ],\n [\n \"1.An integrated image sensor, comprising: a pixel array being responsive to light energy received by the pixel array to produce pixel signals having a voltage level depending on the light energy received by the pixel array; one or more output circuits coupled to the pixel array to access the pixel signals produced by the pixel array; one or more analog-to-digital converters having a first dynamic range and a second dynamic range; one or more timing and control circuits coupled to the pixel array, said one or more output circuits, said one or more analog-to-digital converters or a combination thereof, wherein said one or more timing and control circuits are arranged to: capture, by the pixel array, a structured-light image formed on a common image plane during a first frame period by applying first reset signals to the pixel array to reset rows of pixels of the pixel array, exposing the rows of pixels of the pixel array to structured light to cause first analog signals from the rows of pixels, and converting the first analog signals from the rows of pixels of the pixel array into first digital outputs for the structured-light image using one or more analog-to-digital converters; and capture, by the pixel array, a regular image formed on the common image plane during a second frame period longer than the first frame period by applying second reset signals to the pixel array to reset the rows of pixels of the pixel array, exposing the rows of pixels to non-structured light to cause second analog signals from the rows of pixels, and converting the second analog signals from the rows of pixels into second digital outputs for the regular image using said one or more analog-to-digital converters; and wherein the structured-light image is captured before or after the regular image to derive depth or shape information for the regular image.\",\n \"2.The integrated image sensor of claim 1, wherein said one or more analog-to-digital converters correspond to a configurable analog-to-digital converter to provide both the first dynamic range and the second dynamic range.\",\n \"3.The integrated image sensor of claim 1, wherein said one or more analog-to-digital converters correspond to two analog-to-digital converters with two different resolutions to provide both the first dynamic range and the second dynamic range.\",\n \"4.The integrated image sensor of claim 1, wherein said one or more timing and control circuits are further arranged to cause the structured-light image to be captured at lower spatial resolution than the regular image.\",\n \"5.An endoscope, comprising: a pixel array being responsive to light energy received by the pixel array to produce pixel signals having a voltage level depending on the light energy received by the pixel array; a structured light source; a non-structured light source; one or more output circuits coupled to the pixel array to access the pixel signals produced by the pixel array; one or more analog-to-digital converters having a first dynamic range and a second dynamic range; one or more timing and control circuits, wherein said one or more timing and control circuits are coupled to the pixel array, said one or more output circuits, said one or more analog-to-digital converters, or a combination thereof, wherein said one or more timing and control circuits are arranged to: capture, by the pixel array, a structured-light image formed on a common image plane during a first frame period by applying first reset signals to the pixel array to reset rows of pixels of the pixel array, exposing the rows of pixels of the pixel array to first illumination from the structured light source to cause first analog signals from the rows of pixels and converting the first analog signals from the rows of pixels of the pixel array into first digital outputs for the structured-light image using one or more analog-to-digital converters; and capture, by the pixel array, a regular image formed on the common image plane during a second frame period longer than the first frame period by applying second reset signals to the pixel array to reset the rows of pixels of the pixel array, exposing the rows of pixels to second illumination from the non-structured light source to cause second analog signals from the rows of pixels, and converting the second analog signals from the rows of pixels into second digital outputs for the regular image using said one or more analog-to-digital converters; and wherein the structured-light image is captured before or after the regular image to derive depth or shape information for the regular image.\",\n \"6.The endoscope of claim 5 further comprising a capsule housing adapted to be swallowed, wherein the pixel array, the structured light source, the non-structured light source, said one or more output circuits, and said one or more timing and control circuits are enclosed and sealed in the capsule housing.\",\n \"7.The endoscope of claim 5, wherein said one or more analog-to-digital converters correspond to a configurable analog-to-digital converter to provide both the first dynamic range and the second dynamic range.\",\n \"8.The endoscope of claim 5, wherein said one or more analog-to-digital converters correspond to two analog-to-digital converters with two different resolution to provide both the first dynamic range and the second dynamic range.\",\n \"9.The endoscope of claim 5, wherein the structured-light image is captured at lower spatial resolution than the regular image.\",\n \"10.A camera system, comprising: a pixel array being responsive to light energy received by the pixel array to produce pixel signals data having a voltage level depending on the light energy received by the pixel array; a structured light source; a non-structured light source; one or more output circuits coupled to the pixel array to access pixel signals produced by the pixel array; one or more analog-to-digital converters having a first dynamic range and a second dynamic range; one or more timing and control circuits coupled to the pixel array, said one or more output circuits, said one or more analog-to-digital converters, the structured light source, the non-structured light source, or a combination thereof, wherein said one or more timing and control circuits are configured to: capture, by the pixel array, a structured-light image formed on a common image plane during a first frame period by applying first reset signals to the pixel array to reset rows of pixels of the pixel array, exposing the rows of pixels of the pixel array to first illumination from the structured light source to cause first analog signals from the rows of pixels and converting the first analog signals from the rows of pixels of the pixel array into first digital outputs for the structured-light image using one or more analog-to-digital converters; and capture, by the pixel array, a first regular image formed on the common image plane during a second frame period by applying second reset signals to the pixel array to reset the rows of pixels of the pixel array, exposing the rows of pixels to second illumination from the non-structured light source to cause second analog signals from the rows of pixels, and converting the second analog signals from the rows of pixels into second digital outputs for the first regular image using said one or more analog-to-digital converters; and capture, by the pixel array, a second regular image formed on the common image plane during a third frame period by applying third reset signals to the pixel array to reset the rows of pixels of the pixel array, exposing the rows of pixels to the second illumination from the non-structured light source to cause third analog signals from the rows of pixels, and converting the third analog signals from the rows of pixels into third digital outputs for the second regular image using said one or more analog-to-digital converters; combine the second digital outputs and the third digital outputs to form a combined regular image; and wherein the structured-light image is captured between the first regular image and the second regular image to derive depth or shape information for the combined regular image, and the first frame period is shorter than a sum of the second frame period and the third frame period.\",\n \"11.The camera system of claim 10, wherein the structured-light image is captured at lower spatial resolution than the first regular image and the second regular image.\",\n \"12.The camera system of claim 10, wherein said one or more analog-to-digital converters correspond to a configurable analog-to-digital converter to provide both the first dynamic range and the second dynamic range.\",\n \"13.The camera system of claim 10, wherein said one or more analog-to-digital converters correspond to two analog-to-digital converters with two different resolutions to provide both the first dynamic range and the second dynamic range.\",\n \"14.An endoscope for in vivo viewing, comprising: a pixel array being responsive to light energy received by the pixel array to produce pixel signals having a voltage level depending on the light energy received by the pixel array; a structured light source; a non-structured light source; one or more output circuits coupled to the pixel array to access the pixel signals produced by the pixel array; one or more analog-to-digital converters having a first dynamic range and a second dynamic range; one or more timing and control circuits coupled to the pixel array, said one or more output circuits, said one or more analog-to-digital converters, the structured light source, the non-structured light source, or a combination thereof, wherein said one or more timing and control circuits are configured to: capture, by the pixel array, a structured-light image formed on a common image plane during a first frame period by applying first reset signals to the pixel array to reset rows of pixels of the pixel array, exposing the rows of pixels of the pixel array to first illumination from the structured light source to cause first analog signals from the rows of pixels and converting the first analog signals from the rows of pixels of the pixel array into first digital outputs for the structured-light image using one or more analog-to-digital converters; and capture, by the pixel array, a first regular image formed on the common image plane during a second frame period by applying second reset signals to the pixel array to reset the rows of pixels of the pixel array, exposing the rows of pixels to an ambient light or second illumination from the non-structured light source to cause second analog signals from the rows of pixels, and converting the second analog signals from the rows of pixels into second digital outputs for the first regular image using said one or more analog-to-digital converters; and capture, by the pixel array, a second regular image formed on the common image plane during a third frame period by applying third reset signals to the pixel array to reset the rows of pixels of the pixel array, exposing the rows of pixels to the ambient light or the second illumination from the non-structured light source to cause third analog signals from the rows of pixels, and converting the third analog signals from the rows of pixels into third digital outputs for the second regular image using said one or more analog-to-digital converters; combine the second digital outputs and the third digital outputs to form a combined regular image; and wherein the structured-light image is captured between the first regular image and the second regular image, and the first frame period is shorter than a sum of the second frame period and the third frame period.\",\n \"15.The endoscope of claim 14, wherein the structured-light image is captured at lower spatial resolution than the first regular image and the second regular image.\",\n \"16.The endoscope of claim 14, wherein said one or more analog-to-digital converters correspond to a configurable analog-to-digital converter to provide both the first dynamic range and the second dynamic range.\",\n \"17.The endoscope of claim 14, wherein said one or more analog-to-digital converters correspond to two analog-to-digital converters with two different resolution to provide both the first dynamic range and the second dynamic range.\",\n \"18.The endoscope of claim 14 further comprising a capsule housing adapted to be swallowed, wherein the pixel array, the structured light source, the non-structured light source, said one or more output circuits, and said one or more timing and control circuits are enclosed and sealed in the capsule housing.\"\n ],\n [\n \" BACKGROUND AND RELATED ART Devices for imaging body cavities or passages in vivo are known in the art and include endoscopes and autonomous encapsulated cameras.\",\n \"Endoscopes are flexible or rigid tubes that pass into the body through an orifice or surgical opening, typically into the esophagus via the mouth or into the colon via the rectum.\",\n \"An image is formed at the distal end using a lens and transmitted to the proximal end, outside the body, either by a lens-relay system or by a coherent fiber-optic bundle.\",\n \"A conceptually similar instrument might record an image electronically at the distal end, for example using a CCD or CMOS array, and transfer the image data as an electrical signal to the proximal end through a cable.\",\n \"Endoscopes allow a physician control over the field of view and are well-accepted diagnostic tools.\",\n \"Capsule endoscope is an alternative in vivo endoscope developed in recent years.\",\n \"For capsule endoscope, a camera is housed in a swallowable capsule, along with a radio transmitter for transmitting data, primarily comprising images recorded by the digital camera, to a base-station receiver or transceiver and data recorder outside the body.\",\n \"The capsule may also include a radio receiver for receiving instructions or other data from a base-station transmitter.\",\n \"Instead of radio-frequency transmission, lower-frequency electromagnetic signals may be used.\",\n \"Power may be supplied inductively from an external inductor to an internal inductor within the capsule or from a battery within the capsule.\",\n \"An autonomous capsule camera system with on-board data storage was disclosed in the U.S. Pat.\",\n \"No.\",\n \"7,983,458, entitled “In Vivo Autonomous Camera with On-Board Data Storage or Digital Wireless Transmission in Regulatory Approved Band,” granted on Jul.\",\n \"19, 2011.The capsule camera with on-board storage archives the captured images in on-board non-volatile memory.\",\n \"The capsule camera is retrieved upon its exiting from the human body.\",\n \"The images stored in the non-volatile memory of the retrieved capsule camera are then accessed through an output port on in the capsule camera.\",\n \"While the two-dimensional images captured by the endoscopes have been shown useful for diagnosis, it is desirable to be able to capture gastrointestinal (GI) tract images with depth information (i.e., three-dimensional (3D) images) to improve the accuracy of diagnosis or to ease the diagnosis process.\",\n \"In the field of 3D imaging, 3D images may be captured using a regular camera for the texture information in the scene and a separate depth camera (e.g.\",\n \"Time of Flight camera) for the depth information of the scene in the field of view.\",\n \"The 3D images may also be captured using multiple cameras, where multiple cameras are often used in a planar configuration to capture a scene from different view angles.\",\n \"Then, point correspondence is established among multiple views for 3D triangulation.\",\n \"Nevertheless, these multi-camera systems may not be easily adapted to the GI tract environment, where the space is very limited.\",\n \"In the past twenty years, a structured light technology has been developed to derive the depth or shape of objects in the scene using a single camera.\",\n \"In the structured light system, a light source, often a projector is used to project known geometric pattern(s) onto objects in the scene.\",\n \"A regular camera can be used to capture images with and without the projected patterns.\",\n \"The images captured with the structured light can be used to derive the shapes associated with the objects in the scene.\",\n \"The depth or shape information is then used with regular images, which are captured with non-structured floodlit light, to create 3D textured model of the objects.\",\n \"The structured light technology has been well known in the field.\",\n \"For example, in “ Structured - light 3 D surface imaging: a tutorial ” (Geng, in Advances in Optics and Photonics , Vol.\",\n \"3, Issue 2, pp.\",\n \"128-160, Mar.\",\n \"31, 2011), structured light technology using various structured light patterns are described and the corresponding performances are compared.\",\n \"In another example, various design, calibration and implement issues are described in “3-D Computer Vision Using Structured Light: Design, Calibration and Implementation Issues” (DePiero et al., Advances in Computers , Volume 43, Jan. 1, 1996, pages 243-278).\",\n \"Accordingly, the details of the structured light technology are not repeated here.\",\n \"While the structured light technology may be more suitable for 3D imaging of the GI tract than other technologies, there are still issues with the intended application for GI tract.\",\n \"For example, most of the structured light applications are intended for stationary object.\",\n \"Therefore, there is no object movement between the captured structured-light image and the regular image.\",\n \"Nevertheless, in the capsule camera application for GI tract imaging, both the capsule camera and the GI parts (e.g.\",\n \"small intestines and colons) may be moving.\",\n \"Therefore, there will be relative movement between the structured-light image and the regular image if they are captured consecutively.\",\n \"Furthermore, the capsule camera application is a very power-sensitive environment.\",\n \"The use of structured light will consume system power in addition to capturing the regular images.\",\n \"Besides, if one image with structured light is taken after each regular image, the useful frame rate will be dropped to half.\",\n \"If the same frame rate of regular images is maintained, the system would have to capture images at twice the regular frame rate and consume twice the power in image capture.\",\n \"Accordingly, it is desirable to develop technology for structured light application in the GI tract that can overcome these issues mentioned here.\"\n ],\n [\n \" BRIEF SUMMARY OF THE INVENTION An integrated image sensor for capturing a mixed structured-light image and regular image using an integrated image sensor are disclosed.\",\n \"The integrated image sensor comprises a pixel array being responsive to light energy received by the pixel array to produce pixel signals having a voltage level depending on the light energy received by the pixel array; one or more output circuits coupled to the pixel array to access the pixel signals produced by the pixel array; one or more analog-to-digital converters having a first dynamic range and a second dynamic range; and one or more timing and control circuits coupled to the pixel array, said one or more output circuits, said one or more analog-to-digital converters, or a combination thereof.\",\n \"The timing and control circuits are arranged to perform a set of actions including capturing a structured-light image formed on a common image plane during a first frame period by applying first reset signals to the pixel array to reset rows of pixels of the pixel array, exposing the rows of pixels of the pixel array to structured light to cause first analog signals from the rows of pixels, and converting the first analog signals from the rows of pixels of the pixel array into first digital outputs for the structured-light image using one or more analog-to-digital converters; and capturing, by the pixel array, a regular image formed on the common image plane during a second frame period longer than the first frame period by applying second reset signals to the pixel array to reset the rows of pixels of the pixel array, exposing the rows of pixels to non-structured light to cause second analog signals from the rows of pixels, and converting the second analog signals from the rows of pixels into second digital outputs for the regular image using said one or more analog-to-digital converters.\",\n \"According to the present invention, the structured-light image is captured before or after the regular image to derive depth or shape information for the regular image.\",\n \"In one embodiment, the analog-to-digital converters may correspond to a configurable analog-to-digital converter to provide both the first dynamic range and the second dynamic range.\",\n \"In another embodiment, the analog-to-digital converters may correspond to two analog-to-digital converters with two different resolutions to provide both the first dynamic range and the second dynamic range.\",\n \"In yet another embodiment, the timing and control circuits are further arranged to cause the structured-light image to be captured at lower spatial resolution than the regular image.\",\n \"An endoscope based on the above integrated image sensor is also disclosed.\",\n \"The endoscope further comprises a structured light source and a non-structured light source, which may be coupled to the timing and control circuits.\",\n \"For capturing a structured-light image, the rows of pixels of the pixel array may be exposed to first illumination from the structured light source to cause first analog signals from the rows of pixels and the first analog signals from the rows of pixels of the pixel array are converted into first digital outputs for the structured-light image using one or more analog-to-digital converters.\",\n \"For capturing a regular image formed on the common image plane, the rows of pixels may be exposed to second illumination from the non-structured light source to cause second analog signals from the rows of pixels, and the second analog signals from the rows of pixels are converted into second digital outputs for the regular image using said one or more analog-to-digital converters.\",\n \"The endoscope may further comprises a capsule housing adapted to be swallowed, where the pixel array, the structured light source, the non-structured light source, said one or more output circuits, and said one or more timing and control circuits are enclosed and sealed in the capsule housing.\",\n \"A camera system for capturing a structured-light image between two regular images is also disclosed.\",\n \"The camera system comprises a pixel array, a structured light source, a non-structured light source, one or more output circuits, one or more analog-to-digital converters and one or more timing and control circuits.\",\n \"A combined regular image is derived based on a first regular captured before the structured-light image and a second regular captured after the structured-light image.\",\n \"Depth or shape information derived from the structured-light image is used for the combined regular image.\",\n \"An endoscope based on the above camera system is disclosed.\",\n \"The endoscope may further comprises a capsule housing adapted to be swallowed, where the pixel array, the structured light source, the non-structured light source, said one or more output circuits, and said one or more timing and control circuits are enclosed and sealed in the capsule housing.\"\n ],\n [\n \"CROSS REFERENCES The present application is a divisional application of and claims the priority to U.S. Non-Provisional application Ser.\",\n \"No.\",\n \"14/884,788, filed on Oct. 16, 2015.The U.S. Non-Provisional application is incorporated by reference in its entirety.\",\n \"FIELD OF THE INVENTION The present invention relates to a single image sensor capable of capturing structured-light images and regular image, where the structured-light image is used to derive depth or shape information related to the corresponding regular image.\",\n \"BACKGROUND AND RELATED ART Devices for imaging body cavities or passages in vivo are known in the art and include endoscopes and autonomous encapsulated cameras.\",\n \"Endoscopes are flexible or rigid tubes that pass into the body through an orifice or surgical opening, typically into the esophagus via the mouth or into the colon via the rectum.\",\n \"An image is formed at the distal end using a lens and transmitted to the proximal end, outside the body, either by a lens-relay system or by a coherent fiber-optic bundle.\",\n \"A conceptually similar instrument might record an image electronically at the distal end, for example using a CCD or CMOS array, and transfer the image data as an electrical signal to the proximal end through a cable.\",\n \"Endoscopes allow a physician control over the field of view and are well-accepted diagnostic tools.\",\n \"Capsule endoscope is an alternative in vivo endoscope developed in recent years.\",\n \"For capsule endoscope, a camera is housed in a swallowable capsule, along with a radio transmitter for transmitting data, primarily comprising images recorded by the digital camera, to a base-station receiver or transceiver and data recorder outside the body.\",\n \"The capsule may also include a radio receiver for receiving instructions or other data from a base-station transmitter.\",\n \"Instead of radio-frequency transmission, lower-frequency electromagnetic signals may be used.\",\n \"Power may be supplied inductively from an external inductor to an internal inductor within the capsule or from a battery within the capsule.\",\n \"An autonomous capsule camera system with on-board data storage was disclosed in the U.S. Pat.\",\n \"No.\",\n \"7,983,458, entitled “In Vivo Autonomous Camera with On-Board Data Storage or Digital Wireless Transmission in Regulatory Approved Band,” granted on Jul.\",\n \"19, 2011.The capsule camera with on-board storage archives the captured images in on-board non-volatile memory.\",\n \"The capsule camera is retrieved upon its exiting from the human body.\",\n \"The images stored in the non-volatile memory of the retrieved capsule camera are then accessed through an output port on in the capsule camera.\",\n \"While the two-dimensional images captured by the endoscopes have been shown useful for diagnosis, it is desirable to be able to capture gastrointestinal (GI) tract images with depth information (i.e., three-dimensional (3D) images) to improve the accuracy of diagnosis or to ease the diagnosis process.\",\n \"In the field of 3D imaging, 3D images may be captured using a regular camera for the texture information in the scene and a separate depth camera (e.g.\",\n \"Time of Flight camera) for the depth information of the scene in the field of view.\",\n \"The 3D images may also be captured using multiple cameras, where multiple cameras are often used in a planar configuration to capture a scene from different view angles.\",\n \"Then, point correspondence is established among multiple views for 3D triangulation.\",\n \"Nevertheless, these multi-camera systems may not be easily adapted to the GI tract environment, where the space is very limited.\",\n \"In the past twenty years, a structured light technology has been developed to derive the depth or shape of objects in the scene using a single camera.\",\n \"In the structured light system, a light source, often a projector is used to project known geometric pattern(s) onto objects in the scene.\",\n \"A regular camera can be used to capture images with and without the projected patterns.\",\n \"The images captured with the structured light can be used to derive the shapes associated with the objects in the scene.\",\n \"The depth or shape information is then used with regular images, which are captured with non-structured floodlit light, to create 3D textured model of the objects.\",\n \"The structured light technology has been well known in the field.\",\n \"For example, in “Structured-light 3D surface imaging: a tutorial” (Geng, in Advances in Optics and Photonics, Vol.\",\n \"3, Issue 2, pp.\",\n \"128-160, Mar.\",\n \"31, 2011), structured light technology using various structured light patterns are described and the corresponding performances are compared.\",\n \"In another example, various design, calibration and implement issues are described in “3-D Computer Vision Using Structured Light: Design, Calibration and Implementation Issues” (DePiero et al., Advances in Computers, Volume 43, Jan. 1, 1996, pages 243-278).\",\n \"Accordingly, the details of the structured light technology are not repeated here.\",\n \"While the structured light technology may be more suitable for 3D imaging of the GI tract than other technologies, there are still issues with the intended application for GI tract.\",\n \"For example, most of the structured light applications are intended for stationary object.\",\n \"Therefore, there is no object movement between the captured structured-light image and the regular image.\",\n \"Nevertheless, in the capsule camera application for GI tract imaging, both the capsule camera and the GI parts (e.g.\",\n \"small intestines and colons) may be moving.\",\n \"Therefore, there will be relative movement between the structured-light image and the regular image if they are captured consecutively.\",\n \"Furthermore, the capsule camera application is a very power-sensitive environment.\",\n \"The use of structured light will consume system power in addition to capturing the regular images.\",\n \"Besides, if one image with structured light is taken after each regular image, the useful frame rate will be dropped to half.\",\n \"If the same frame rate of regular images is maintained, the system would have to capture images at twice the regular frame rate and consume twice the power in image capture.\",\n \"Accordingly, it is desirable to develop technology for structured light application in the GI tract that can overcome these issues mentioned here.\",\n \"BRIEF SUMMARY OF THE INVENTION An integrated image sensor for capturing a mixed structured-light image and regular image using an integrated image sensor are disclosed.\",\n \"The integrated image sensor comprises a pixel array being responsive to light energy received by the pixel array to produce pixel signals having a voltage level depending on the light energy received by the pixel array; one or more output circuits coupled to the pixel array to access the pixel signals produced by the pixel array; one or more analog-to-digital converters having a first dynamic range and a second dynamic range; and one or more timing and control circuits coupled to the pixel array, said one or more output circuits, said one or more analog-to-digital converters, or a combination thereof.\",\n \"The timing and control circuits are arranged to perform a set of actions including capturing a structured-light image formed on a common image plane during a first frame period by applying first reset signals to the pixel array to reset rows of pixels of the pixel array, exposing the rows of pixels of the pixel array to structured light to cause first analog signals from the rows of pixels, and converting the first analog signals from the rows of pixels of the pixel array into first digital outputs for the structured-light image using one or more analog-to-digital converters; and capturing, by the pixel array, a regular image formed on the common image plane during a second frame period longer than the first frame period by applying second reset signals to the pixel array to reset the rows of pixels of the pixel array, exposing the rows of pixels to non-structured light to cause second analog signals from the rows of pixels, and converting the second analog signals from the rows of pixels into second digital outputs for the regular image using said one or more analog-to-digital converters.\",\n \"According to the present invention, the structured-light image is captured before or after the regular image to derive depth or shape information for the regular image.\",\n \"In one embodiment, the analog-to-digital converters may correspond to a configurable analog-to-digital converter to provide both the first dynamic range and the second dynamic range.\",\n \"In another embodiment, the analog-to-digital converters may correspond to two analog-to-digital converters with two different resolutions to provide both the first dynamic range and the second dynamic range.\",\n \"In yet another embodiment, the timing and control circuits are further arranged to cause the structured-light image to be captured at lower spatial resolution than the regular image.\",\n \"An endoscope based on the above integrated image sensor is also disclosed.\",\n \"The endoscope further comprises a structured light source and a non-structured light source, which may be coupled to the timing and control circuits.\",\n \"For capturing a structured-light image, the rows of pixels of the pixel array may be exposed to first illumination from the structured light source to cause first analog signals from the rows of pixels and the first analog signals from the rows of pixels of the pixel array are converted into first digital outputs for the structured-light image using one or more analog-to-digital converters.\",\n \"For capturing a regular image formed on the common image plane, the rows of pixels may be exposed to second illumination from the non-structured light source to cause second analog signals from the rows of pixels, and the second analog signals from the rows of pixels are converted into second digital outputs for the regular image using said one or more analog-to-digital converters.\",\n \"The endoscope may further comprises a capsule housing adapted to be swallowed, where the pixel array, the structured light source, the non-structured light source, said one or more output circuits, and said one or more timing and control circuits are enclosed and sealed in the capsule housing.\",\n \"A camera system for capturing a structured-light image between two regular images is also disclosed.\",\n \"The camera system comprises a pixel array, a structured light source, a non-structured light source, one or more output circuits, one or more analog-to-digital converters and one or more timing and control circuits.\",\n \"A combined regular image is derived based on a first regular captured before the structured-light image and a second regular captured after the structured-light image.\",\n \"Depth or shape information derived from the structured-light image is used for the combined regular image.\",\n \"An endoscope based on the above camera system is disclosed.\",\n \"The endoscope may further comprises a capsule housing adapted to be swallowed, where the pixel array, the structured light source, the non-structured light source, said one or more output circuits, and said one or more timing and control circuits are enclosed and sealed in the capsule housing.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS FIG.\",\n \"1 illustrates exemplary analog-to-digital converter with 8-bit dynamic range.\",\n \"FIGS.\",\n \"2A-B illustrate ramp voltage waveforms used as a reference signal for the analog-to-digital converter, where the waveforms shown are for 9-bit (FIG.\",\n \"2A) and 6-bit (FIG.\",\n \"2B) dynamic resolutions.\",\n \"FIG.\",\n \"3 illustrates an exemplary block diagram of a pixel array for capturing a tandem structured-light image and regular image according to an embodiment of the present invention.\",\n \"FIG.\",\n \"4A illustrates an exemplary timing chart for capturing two regular images.\",\n \"FIG.\",\n \"4B illustrates an example of a tandem structured-light image and regular image according to an embodiment of the present invention.\",\n \"FIG.\",\n \"5 illustrates an exemplary timing corresponding to FIG.\",\n \"4B for applying the structured light for capturing a structured-light image according to an embodiment of the present invention, where the structured light duration is explicitly shown and some notations are deleted for clear illustration.\",\n \"FIG.\",\n \"6 illustrates another view of applying the structured light for capturing a structured-light image and capturing a regular image according to an embodiment of the present invention.\",\n \"FIG.\",\n \"7A illustrates exemplary timing charts for capturing a two-session image according to an embodiment of the present invention, where a first regular sub-image is captured in the first session and a mixed image consisting of a structured-light image and a second regular sub-image is captured in the second session, the regular image are combined as the final output and the integration period for the first session is approximately the same as the integration period for the second session.\",\n \"FIG.\",\n \"7B illustrates exemplary timing charts similar to these of FIG.\",\n \"7A, where the integration period for the first session is approximately three times as long as the integration period for the second session.\",\n \"FIG.\",\n \"8 illustrates an exemplary flowchart for capturing a tandem structured-light image and regular image according to an embodiment of the present invention, where the structured-light image has lower dynamic range than the regular image.\",\n \"FIG.\",\n \"9 illustrates an exemplary flowchart for capturing a tandem structured-light image and regular image according to another embodiment of the present invention, where the structured-light image has lower dynamic range than the regular image.\",\n \"DETAILED DESCRIPTION OF THE INVENTION It will be readily understood that the components of the present invention, as generally described and illustrated in the figures herein, may be arranged and designed in a wide variety of different configurations.\",\n \"Thus, the following more detailed description of the embodiments of the systems and methods of the present invention, as represented in the figures, is not intended to limit the scope of the invention, as claimed, but is merely representative of selected embodiments of the invention.\",\n \"References throughout this specification to “one embodiment,” “an embodiment,” or similar language mean that a particular feature, structure, or characteristic described in connection with the embodiment may be included in at least one embodiment of the present invention.\",\n \"Thus, appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment.\",\n \"Furthermore, the described features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.\",\n \"One skilled in the relevant art will recognize, however, that the invention can be practiced without one or more of the specific details, or with other methods, components, etc.\",\n \"In other instances, well-known structures, or operations are not shown or described in detail to avoid obscuring aspects of the invention.\",\n \"The illustrated embodiments of the invention will be best understood by reference to the drawings, wherein like parts are designated by like numerals throughout.\",\n \"The following description is intended only by way of example, and simply illustrates certain selected embodiments of apparatus and methods that are consistent with the invention as claimed herein.\",\n \"Endoscopes are normally inserted into the human body through a natural opening such as the mouth or anus.\",\n \"Therefore, endoscopes are preferred to be small sizes so as to be minimally invasive.\",\n \"To derive or capture the depth or shape information while capturing live images or videos of the GI tract with endoscopes, it is crucial to maintain the small-size form factor.\",\n \"Besides, with the small size and the capability to capture depth information along with corresponding images or video, such camera also finds its applications in other applications requiring compact size, such as a wearable devices.\",\n \"One technique that may capture depth information is to use a color filter placed on top of selected sensor pixels with the passband reasonably narrow and capture the color information and depth information simultaneously.\",\n \"The environment light sources with spectrum in the filter passband will cause negligible amount of energy projected onto the sensor.\",\n \"For the case of RGB pixels, a fourth type of pixels may be added to capture light with the spectrum in the passband of the filter placed on top of these pixels.\",\n \"Then, the structured light that has the spectrum substantially in the passband can be projected onto the scene.\",\n \"However this approach will reduce the spatial resolution of the images or video captured using such image sensor.\",\n \"Another technique is to obtain the depth information as well as 3D topology by projecting structured light patterns that are visible in the RGB sensors.\",\n \"However the real time image and/or video will be confounded by the structured light superimposed on it.\",\n \"This invention describes methods to use a single camera to achieve depth information by using the structured light approach while taking images or real time video using the camera.\",\n \"As mentioned before, a conventional structured light approach with a single camera would incur several drawbacks.\",\n \"For example, the camera with a frame rate of 30 frames per second may be used.\",\n \"A conventional approach would take live video with interleaved images corresponding to images with and without the structured light.\",\n \"One issue is that the depth information is 1/30 second away from corresponding images to be viewed.\",\n \"If there is any movement in the scene, the depth information may not accurately represent the 3D topology of the corresponding images at 1/30 second away.\",\n \"In addition, the effective frame rate for the video to be viewed is dropped to 15 frames per second in this example.\",\n \"In some video applications, the frame rate is crucial for the intended application.\",\n \"For example, a high frame-rate camera with frame rate in the 100's per second or more is required to capture video of fast moving objects such as a travelling bullet.\",\n \"In this case, the use of structured light would cut the frame rate to half and may hinder the intended application.\",\n \"For a capsule camera, the video for the gastrointestinal (GI) tract is normally a few frames per second and the camera could be operating at twice the original frame rate to compensate the reduction of effective frame rate due to capturing structured-light images.\",\n \"However, it would result in twice as much power consumption, which is not desirable in the power-limited capsule environment.\",\n \"Each frame rate has a corresponding frame period.\",\n \"During the frame period, the sensor will spend a subset of the frame period for accumulating charges emitted in response to incidental light on the sensor.\",\n \"The integration time must be sufficiently small so that the image is substantially stationary to avoid causing any motion blur in the captured image.\",\n \"FIG.\",\n \"1 illustrates an example of ADC (analog-to-digital converter) that can be used for an image sensor.\",\n \"The ADC includes a comparator (110) to compare an input analog signal (120) with a reference signal (130).\",\n \"The analog signal (120) from the analog circuits connected to a pixel is coupled to one terminal of the comparator to compare with a ramp voltage.\",\n \"In one embodiment, the ramp voltage can be generated using a clock that is used for digital logic circuits so that the ramp voltage goes one step higher according to each driving clock.\",\n \"FIG.\",\n \"2A and FIG.\",\n \"2B show two examples of ramp voltage corresponding to 9-bit (i.e., 512 levels) and 6-bit (i.e., 64 levels) respectively.\",\n \"The same clock supplied to generate the ramp voltage is also counted by the counter (140).\",\n \"When the ramp voltage level reaches the analog signal (120) from the pixel analog readout circuits connected to a pixel, the comparator output will switch (e.g.\",\n \"from high to low or low to high) to indicate the event.\",\n \"At the same time, the comparator output signal will trigger the registers (150) so as to latch a counter value that counts the number of clocks indicating the ramp voltage value crossing the analog signal (120).\",\n \"The output from the pixel is often measured twice using the correlated double sampling (CDS) technique, which is well known in the field to take care of the fixed pattern noise due to manufacturing variation among pixels.\",\n \"The offset reset signal can be removed using analog circuits (e. g. correlated double sampling) or digital circuits.\",\n \"For digital implementation, the digital counter readout after reset can be subtracted from the digital counter readout of a pixel after an integration period.\",\n \"There are several factors determining how fast the pixel can accumulate electronic charges and how fast the signal can be readout.\",\n \"As shown in the example of FIG.\",\n \"1, the analog output signal (120) from analog circuits connected to each pixel is compared to a reference signal (i.e., the voltage ramp).\",\n \"Depending on the desired digital pixel resolution (e.g.\",\n \"9 bits vs 6 bits), a corresponding ramp signal can be generated.\",\n \"The readout speed will depend on the speed of the counter, the comparator and other related circuits.\",\n \"The ramp signal corresponding to higher digital resolution (i.e., higher dynamic range) will take longer time to generate.\",\n \"The implementation to support 6-bit digital dynamic range as shown in FIG.\",\n \"2B will be 8 times faster than the implementation for digital 9-bit dynamic range as shown in FIG.\",\n \"2A.\",\n \"There are other variations to implement ADC, such as successive approximation ADC.\",\n \"For the successive approximation ADC, the reference voltage starts with a coarse level.\",\n \"Depending on whether the input voltage is higher or lower than the reference voltage, the reference voltage is refined by increasing or decreasing the previous reference voltage by half of a previous voltage interval.\",\n \"The refined reference voltage is used as a current reference voltage for next successive comparison.\",\n \"The process is terminated until a desired resolution is achieved.\",\n \"In each round of successive approximation, one bit is used to indicate whether the input voltage is higher or lower than the reference voltage.\",\n \"Accordingly, the ADC resolution corresponds to the number of successive approximation of the successive-approximation ADC.\",\n \"In general, the higher the dynamic ranges, the longer the readout will be.\",\n \"Not only more comparisons will be required, but also the voltage will take longer time to settle down since the accuracy requirements of the ramp up voltage or reference voltages are high.\",\n \"The sensor array has a large intrinsic RC constant, which takes time to settle to within the limits required by the accuracy.\",\n \"In the case of a high dynamic range, the conductor line carrying the reference voltage (i.e., the ramp reference signal) requires more time to settle due to the inductance, along with R (resistance) and C (capacitance), of the conductor line.\",\n \"The length of the conductor line for the sensor array usually is in the order of 1,000's μm (micro meter), which may result in an inductance around a few nH (nano Henry).\",\n \"Unlike resistance, the inductance will not be scaled down inversely proportional to the conductor cross section.\",\n \"The high dynamical range is an important factor for image/video quality to provide detailed shades of the objects in the scene.\",\n \"On the other hand, the images for structured light pattern are mainly used to derive depth/shape information based on the geometric information of know patterns, such as grids.\",\n \"The important information to be derived is related to the locations of the grid lines.\",\n \"Accordingly, the requirement on the dynamic range is substantially lower than that for the regular images to be viewed by the human eyes.\",\n \"Since the required dynamic range for the structured-light image is much less than that for a regular image, the present invention takes advantage of the different dynamic range requirements to shorten the frame period for the structured-light image.\",\n \"FIG.\",\n \"3 illustrates a simplified system block diagram of an integrated image sensor incorporating an embodiment of the present invention.\",\n \"The integrated image sensor comprises a pixel array (310) being responsive to light energy received by the pixel array to produce signal data having a voltage level depending on the light energy received, output circuits (320) coupled to the pixel array to access the signal data produced by the pixel array, one or more analog-to-digital converters (ADCs, 330) having a first dynamic range and a second dynamic range, and timing/control circuits (340a and 340b).\",\n \"The pixel array may consist of monochrome pixels or color pixels.\",\n \"The pixel array can be based on the CMOS technology or the CCD technology.\",\n \"The output circuits are coupled to the pixel array under the control of the timing/control circuits.\",\n \"For example, the pixel array outputs can be transferred to the output circuits row by row under the control of the timing/control circuits.\",\n \"The output circuits may also include amplifier and CDS circuit, where the CDS circuit is used to take care of the offset in individual pixels after reset.\",\n \"While the timing/control circuits (340a and 340b) are shown as two separate blocks, they may also be implemented as a unified block.\",\n \"The ADC circuit(s) is capable of operating at a first dynamic range and a second dynamic range.\",\n \"The first dynamic range is smaller than the second dynamic range.\",\n \"For example, the first dynamic range may correspond to 6 bits and the second dynamic range may correspond to 9 bits.\",\n \"Individual ADCs with different dynamic ranges may be used.\",\n \"Since the structured-light image and the regular image are captured in serial instead of parallel, a single ADC with configurable dynamic range may also be used.\",\n \"For example, an adaptively configurable ADC is disclosed in U.S. Pat.\",\n \"No.\",\n \"8,369,458 issued to Wong et al.\",\n \"on Feb. 5, 2013.The timing/control circuits may include row scan circuit and column scan circuit.\",\n \"The timing/control circuits are also responsible to generate various control signals such as reset signals.\",\n \"In the following, preferred embodiments are provided regarding configuring the image sensor to capture structured-light images and regular images.\",\n \"FIG.\",\n \"4A illustrates an example of the timing for a regular image sensor, where the row timing is shown from frame to frame in the horizontal direction and from the first row (top) to the last row (bottom) in the vertical direction.\",\n \"In a typical image sensor, the image pixels are read out row by row.\",\n \"There are several phases of operation for each row including row reset, integration and readout.\",\n \"The operations usually are staggered from row to row as shown in FIG.\",\n \"4A.\",\n \"However, the readout operation for a current row has to wait until the previous row readout is complete.\",\n \"For a regular image sensor, the similar timing patterns just repeat from frame to frame with the same frame time.\",\n \"The period time is the same for all frames.\",\n \"FIG.\",\n \"4A illustrates the general timing diagram for a typical image sensor.\",\n \"The timing charts may not be drawn to scale.\",\n \"FIG.\",\n \"4B illustrates an example of the timing for capturing a mixed structured-light image and regular image according to one embodiment of the present invention, where the structured light is taken with smaller dynamic range.\",\n \"The frame duration for the structured-light image is much shorter than the frame duration of the following regular image as illustrated in FIG.\",\n \"4B.\",\n \"The timing charts in FIG.\",\n \"4B are not drawn to scale, particularly for the structured light section.\",\n \"The section for the structured light has been expanded in order to illustrate more details.\",\n \"In FIG.\",\n \"4B, the timing signals associated with the structured-light image are shown in Bold-Italic font.\",\n \"The less dynamic range can be achieved, for example, by fewer comparisons with the reference voltage generated by ramping up voltage with a larger step as illustrated in FIGS.\",\n \"2A and 2B.\",\n \"Alternatively, the reference voltage can be generated with a smaller ramp range between the starting voltage and the ending voltage.\",\n \"Since the readout is faster for this structured-light image than the regular image, the structured-light image could be squeezed within the reset timing period of the regular image.\",\n \"Since the structure light image does not need a dynamic range as high as the regular image, the structure light image reset does not need to be as thorough as that for regular image.\",\n \"Therefore, a shorter reset time could be used for the structured light.\",\n \"Accordingly, in one embodiment, the minimum row reset time among the rows of pixels of the image sensor for the structured-light image can be substantially shorter than the minimum row reset time among the rows of pixels of the image sensor for the regular image.\",\n \"FIG.\",\n \"5 is identical to FIG.\",\n \"4B with some notations eliminated to conveniently demonstrate the timing setup.\",\n \"The duration for the structured light is indicated.\",\n \"The structured light duration could be substantially close to the end of first row integration phase for the structured light.\",\n \"On the other hand, the structured light duration must be within the integration phase of the last row for the structured-light image.\",\n \"The optimal structure light pulse duration is from the start of last row integration to the start of first row readout.\",\n \"In order to speed up the operation of capturing a structured-light image, as well as to reduce the impact of the energy of the other light sources, such as ambient light, in the scene entering the camera, the structured light duration is set to be very short.\",\n \"If the integration requires a longer time than desired, the structural light pulse energy can be increased by increasing either the intensity or the duration.\",\n \"In a preferred embodiment, the structured light intensity is substantially stronger compared with the light intensity from the regular light source or ambient light.\",\n \"However, the structured light can be applied for a substantially shorter period than the human visual retention time, making the image of the scene exposed by non-structured light relatively weaker and the signal/noise ratio much stronger for the structure light.\",\n \"The non-structured light may correspond to a broadband, narrowband, or fluoroscopic light.\",\n \"The energy of the structure light pulse may be limited by system power constraints or by a desire not to annoy, distract, or eye-damage persons in the scene exposed to the structured light.\",\n \"Another energy limitation may be a tissue-damage optical-energy threshold in medical-imaging applications.\",\n \"The sensor analog gain may be increased so that the pixel luminance resulting from structured light illumination is well above background noise and luminance from other light sources while the structured light energy is at an acceptably low level.\",\n \"Increased gain results in greater noise amplification and reduced sensor dynamic range.\",\n \"While the main intended application is for the GI tract, the usage of short-duration and high-intensity structured light can also benefit the non-GI applications.\",\n \"For example, the present invention may also be applied to conventional photography to capture mixed regular images and structured-light images of natural scenes and use the depth or shape information derived from the structured images to render 3D images of the scene.\",\n \"In order to derive more reliable depth or shape information using the structured-light images, it is desirable to select a structured-light source having light spectrum very different from the color spectrum of the underlying scene captured under ambient light or illuminated by one or more non-structured lights.\",\n \"While there are readout schemes that may start to read the higher (i.e., most significant) bits during integration, the readout with a larger dynamic range will take a longer time to complete the readout.\",\n \"This is due to more comparisons and longer reference voltage settling time needed.\",\n \"Accordingly, reducing the dynamic range for the structured-light image will be able to reduce the row processing duration.\",\n \"This is also true for image sensors operated in the global shutter mode.\",\n \"Accordingly, the settling time associated with a reference voltage, provided to the analog-to-digital converters to compare with an input analog voltage, is shorter for the first structured-light image than for the regular image.\",\n \"Due to the less accuracy required, the reset signal does not need to be held for so long to reset the pixels and/or related circuits to an optimal level.\",\n \"As shown in FIG.\",\n \"5, the structured light is preferred to be applied at a specific time so that the duration is short, but the short duration covers at least a portion of integration time for all pixel rows.\",\n \"The control signal to trigger the structured light may be derived from the frame signal and the clock.\",\n \"However, the control signal for the structured light may also come from other module of the integrated sensor.\",\n \"In another implementation, a fixed or programmable delay for the control signal from the sensor can be used to adjust the timings to match optimal system design.\",\n \"In one embodiment, the structured light is generated using multiple light sources with at least two different colors or patterns.\",\n \"By using multiple colors, a color or a combination of colors can be selected to cause the light spectrum of the selected color(s) substantially different from the color spectrum of associated with regular images of an anticipated scene illuminated by the non-structured light or under ambient light.\",\n \"The spectrum associated with the structured light can be substantially distinct from the spectrum associated with regular images of an anticipated scene.\",\n \"The image sensor may correspond to a color image sensor comprising at least first and second color pixels arranged in a mosaic pattern, and the spectrum associated with the structured light can be substantially concentrated on the spectrum of first or second color pixels.\",\n \"The structured-light image can be captured at reduced spatial resolution by reading out only selected digital outputs related to the first or second pixels having spectrum substantially corresponding to the structured-light spectrum.\",\n \"For capsule applications, the integrated image sensor may be inside a sealed capsule housing for imaging gastrointestinal tract of human body.\",\n \"Since there is no ambient light in the GI tract, the capsule device has to provide both the structured light and the lighting for regular images.\",\n \"In this case, the structured light sources for structured light images and the illumination light sources for regular images can be sealed in the housing.\",\n \"FIG.\",\n \"6 illustrates another perspective of the timing charts corresponding to these in FIG.\",\n \"5, where the image readouts for the structured image and regular images are highlighted using different fill-patterns.\",\n \"The timing signals related to the structured-light image are indicated in FIG.\",\n \"6, where sli-reset corresponds to the structured-light image reset, sli-integration corresponds to the structured-light image integration and sli-readout corresponds to the structured-light image readout.\",\n \"The structured light duration is also indicated in FIG.\",\n \"6, where the structured light is applied during the sli-integration.\",\n \"The whole period for capturing the structured-light image may occur during the reset period of a regular image reset.\",\n \"In the example shown in FIG.\",\n \"6, the reset for the structure light image may be very brief compared to the reset period for a regular image.\",\n \"The timing charts in FIG.\",\n \"6 illustrate the cycles for capturing a tandem structured-light image and regular image, where the timing for the regular image is modified.\",\n \"In particular, the reset period of the regular image capture is substantially reduced to accommodate the capture of the structured-light image.\",\n \"Accordingly, the timing charts incorporating an embodiment of the present invention shown in FIG.\",\n \"6 can be considered as two separate images or a combo of structured-light image and timing-modified regular image.\",\n \"In the embodiments disclosed above, a structured light image is captured temporally close to a regular image so as to provide more accurate depth/shape information for the associated regular image.\",\n \"In another embodiment, a two-session capture is disclosed, where the regular image is split into two sub-images with a structured light image captured in between.\",\n \"The regular integration time for the regular image is split between the two sub-images.\",\n \"The digital outputs for the two regular sub-images are combined to form a regular image output.\",\n \"This approach has several advantages.\",\n \"First, each sub-image is converted into digital outputs using the ADC that is used for the regular image.\",\n \"Accordingly, each sub-image will have the same dynamic range as the regular image of a one-session approach.\",\n \"When the digital outputs of the two sub-images are combined, the final regular image still preserves the full dynamic range.\",\n \"Assume that a pixel with full integration time would get an analog signal to be digitized into 128.By using half the integration time for each session, the pixel will get half the analog signal amount and thus will be digitized to 64.The half integration time is important because integration time may be a substantial component in the total period.\",\n \"Therefore, by using only half the integration time for each session will cause the total time shorter than otherwise.\",\n \"FIG.\",\n \"7A illustrates an example of two-session approach according to an embodiment of the present invention.\",\n \"In the first session, a regular image can be captured using regular timing.\",\n \"In the second session, a mixed image is captured, which includes a structured-light image and a timing-modified regular image.\",\n \"The structured-light image is captured between the two session readouts.\",\n \"The first session readout may be temporally stored in a memory or buffer inside the image sensor or outside.\",\n \"When the second session readout is complete, the two readout values from two sessions are combined together.\",\n \"Since the structured-light image is captured between the two sub-images of a regular-scene image, the structured-light image should be very close to the captured regular-scene images temporally.\",\n \"Accordingly, the structured-light image should closely correlate to the regular scene image.\",\n \"The readouts from two sub-images associated with the two sessions are combined into one regular image.\",\n \"In one embodiment, a group of interleaved sub-regular images and structured-light images are taken consecutively.\",\n \"For example, the images in odd numbers are for regular images and images in even numbers are for structured-light images.\",\n \"Images 1 and 3, which are two sub-images, could be combined to form a combined regular image corresponding to image 2, which is a structured-light image.\",\n \"Similarly, images 3 and 5, which are two sub-images, could be combined to form a combined regular image corresponding to image 4, which is a structured-light image.\",\n \"Images 5 and 7 could be combined to form a combined regular image corresponding to image 6, which is a structured-light image.\",\n \"The process can continue with each regular sub-image used twice in general.\",\n \"In this case, the weighting factors for images 1, 3, 5, 7, .\",\n \".\",\n \".\",\n \"could be 50/50/50/50 .\",\n \".\",\n \".\",\n \", or it could be 60/40/60/40/60 .\",\n \".\",\n \".\",\n \"with the principle of the two combined weighting is 100 percent of the targeted integration time.\",\n \"In FIG.\",\n \"7A, the integration time for the two sub-images is roughly the same.\",\n \"However, the two integration time may also be different.\",\n \"For example, the integration time for the first sub-image may be three times as long as the integration time (also called integration period in this disclosure) for the second sub-image as shown in FIG.\",\n \"7B.\",\n \"In this case, when the digital outputs from the two sub-images are combined, the combined image has the effect of weighted sum of the first sub-image (i.e., ¾) and the second sub-image (¼).\",\n \"There is no need to perform the weighted sum associated with different integration periods since the weighting will be reflected in the charges accumulated during respective integration periods.\",\n \"The longer integration period results in more accumulated charges, which result in a higher analog signal.\",\n \"Accordingly, the sum of the two digital readouts represents the weighted sum of the two sub-images, where the weighting factors correspond to the integration periods.\",\n \"In another application of structured-light images, multiple structured light images are used to derive more 3D points than a single structured-light image for one or more associated regular images.\",\n \"For example, multiple structured-light images may be captured consecutively by a capsule camera while traversing in the human gastrointestinal (GI) tract.\",\n \"The regular image can be captured between, before or after the multiple structured-light images.\",\n \"The captured structured-light images can be used to derive a 3D model of the GI tract.\",\n \"This 3D GI tract model can be useful for examining associated regular images of the GI tract.\",\n \"For two-session regular image capturing with intervening structured-light image, the means for reducing the frame period for the structured-light image as mentioned before can be used.\",\n \"For example, the structured-light image can be captured with a reduced dynamic range of the image sensor compared to the first regular image and the second regular image.\",\n \"The structured-light image may also be captured at lower spatial resolution than the first regular image and the second regular image.\",\n \"Furthermore, the structured-light image can be captured with a reduced image area in a vertical direction, horizontal direction or both compared to the first regular image and the second regular image.\",\n \"In some cases, the depth or shape information is of interest only for a selected image area.\",\n \"In these cases, the structured-light image can be captured for the selected image area only.\",\n \"Accordingly, it serves an alternative means to reduce the frame period of the structured-light image.\",\n \"The reduced image area may correspond to a reduced image area in the vertical direction, horizontal direction or both compared to the regular image.\",\n \"The means may also be combined with other means, such as reducing the dynamic range or reducing the spatial resolution, for reducing the frame period of the structured-light image.\",\n \"Reducing the spatial resolution by itself can be used as a technique to reduce the frame period for the structured-light images.\",\n \"For example, the structured-light image can be captured with reduced vertical resolution by only retaining selected rows of pixels and skipping remaining rows of pixels of the image sensor.\",\n \"For an endoscope application, including a capsule endoscope application, there is no ambient light and the lighting from the endoscope is the only light source.\",\n \"Therefore, the integration time of each row needs not to be the same as long as the duration of the light exposure is the same for every line.\",\n \"For the endoscope environment, the lower dynamic range of structured-light image than that of the regular image also benefits from temporal proximity between the structured-light image and the regular image.\",\n \"Therefore, the structured-light image according to the present invention should bear more accurate depth or shape information correlated with the regular image.\",\n \"For power sensitive applications such as the capsule endoscope and wearable device, less dynamic range also saves power due to less comparison operations and shorter integration time, which requires less structured light energy.\",\n \"On the other hand, since signal to noise ratio is not so important to structured-light image, its gain can be set to substantial higher to further save energy.\",\n \"A camera system usually includes an exposure control function to control the operating parameters of the image sensor so that the overall intensity of the image taken is at the right level within certain range conducive for viewing.\",\n \"The image intensity is derived from the pixel intensity.\",\n \"The detailed control often is subject to the preference of camera system designer.\",\n \"For example, the image intensity is determined by the average of pixel intensity of central portions of the image.\",\n \"In another example, the mean of the pixel intensity of the central portion is used as the image intensity.\",\n \"In another example, multiple areas of the image are used instead of the central portion.\",\n \"If the intensity is found to be too high, then the gain or the integration time can be reduced.\",\n \"If the intensity is too low then the gain or the integration time can be increased.\",\n \"Furthermore, the amount of adjustment from one image to the next can be dependent on how much the intensity is deviated from the preferred level or range.\",\n \"A camera system may also provide the lighting to augment the ambient light.\",\n \"The lighting from the camera system may also be the sole lighting source, such as a regular endoscope or a capsule endoscope.\",\n \"For a camera used for pipe examination or for deep sea exploration, the lighting from the camera is also the sole lighting source.\",\n \"In such a system, the exposure control will control the gain, integration time, lighting intensity and/or energy or a combination of them.\",\n \"If an image has too strong intensity, the value of (gain×integration×light energy) will be reduced for the subsequent image or images.\",\n \"On the other hand, if an image has too weak intensity, the value of (gain×integration×light energy) will be increased for the subsequent image or images.\",\n \"The amount of adjustment from one image to the next may dependent on much the intensity is deviated from the preferred level or range.\",\n \"An embodiment of the present invention addresses dual exposure controls for capturing structured-light images and regular images using a single image sensor.\",\n \"Based on this embodiment, there are two exposure control loops for the same image sensor, one for the structured-light image and the other for the regular image.\",\n \"In the case that the regular image lighting is substantially dependent on the light controlled by the camera system (e.g.\",\n \"negligible or no ambient light), the exposure condition is very similar for both structured light and the regular light since the distance to the scene is practically the same for both cases.\",\n \"Accordingly, one exposure control loop could be used and the other exposure control is dependent on the first exposure control loop.\",\n \"For example, (gain×integration×light energy) of structure light can be linearly dependent on (gain×integration×light energy) of regular light image or vice versa.\",\n \"In another embodiment, other dependence is used.\",\n \"For example, gamma-type dependence or dependence on the intensity distribution may also be used.\",\n \"In the case where there is ambient light, the structured-light needs to be sufficiently strong to cause the structure light pattern more discernable in the structured-light image for analysis.\",\n \"In this case, the light intensity in the above analysis is composed of ambient light and light or lights projected to the scene controlled by the exposure control of the camera system.\",\n \"In this case, there might be no need for camera control to project light for regular image if ambient light is sufficient.\",\n \"However the structured light has another constraint that the projected structured-light must be strong enough to show its pattern and/or color in the structured-light image.\",\n \"If the spectrum of the structured light is substantially concentrated in the spectrum of one particular color of the image sensor, the intensity of that particular color of the structured light image and/or the overall intensity are considered.\",\n \"In one embodiment, if structured-light sources are capable of generating multiple colors, then the intensity of each color component in the regular image is considered.\",\n \"The structured light source color corresponding to the weaker color in the regular image is chosen in order to make the structured color stand out or to have a higher signal to background ratio statistically for easy analysis FIG.\",\n \"8 illustrates an exemplary flowchart for capturing a mixed structured-light image and regular image according to an embodiment of the present invention.\",\n \"Capturing a first structured-light image using the image sensor during a first frame period in step 810.A regular image is captured using the image sensor during a second frame period, where the first frame period is shorter than the second frame period and the first structured-light image is captured before or after the regular image in step 820.FIG.\",\n \"9 illustrates an exemplary flowchart for capturing a tandem structured-light image and regular image according to one embodiment of the present invention, where the structured-light image has lower dynamic range than the regular image.\",\n \"First reset signals are applied to a pixel array to reset rows of pixels of the pixel array in step 910.The rows of pixels of the image sensor are exposed to structured light to cause first analog signals from the rows of pixels in step 920.The first analog signals from the rows of pixels of the image sensor are converted into first digital outputs for the first structured-light image using one or more analog-to-digital converters in step 930.Second reset signals are applied to the pixel array to reset the rows of pixels of the pixel array in step 940.The rows of pixels are exposed to non-structured light to cause second analog signals from the rows of pixels in step 950.The second analog signals from the rows of pixels are converted into second digital outputs for the regular image using said one or more analog-to-digital converters in step 960.The first structured-light image is captured before or after the regular image in step 960, where the first dynamic range is smaller than the second dynamic range.\",\n \"The invention may be embodied in other specific forms without departing from its spirit or essential characteristics.\",\n \"The described examples are to be considered in all respects only as illustrative and not restrictive.\",\n \"Therefore, the scope of the invention is indicated by the appended claims rather than by the foregoing description.\",\n \"All changes which come within the meaning and range of equivalency of the claims are to be embraced within their scope.\"\n ]\n]"},"source":{"kind":"string","value":"Patent_15871991"}}},{"rowIdx":4493976,"cells":{"text":{"kind":"list like","value":[["SYSTEMS AND METHODS FOR ELECTROSTIMULATION THERAPY","A system for electrostimulation therapy includes two or more electrodes of different metals or metal alloys.","The electrodes can be optionally provided on a flexible non-conducting substrate with a binder, thereby acting as a bandage or patch.","Alternatively, the electrodes can be in the form of a needle, such as acupuncture needle, bracelets, armbands, wristbands, necklaces, or jewelry pieces.","A method for electrostimulation therapy includes the steps of attaching a first electrode to a user or soil of a plant at a first location and attaching at least one additional electrode to the user or the plant at other locations for a predetermined period.","The electrodes are not connected to a voltage or current source.","Because at least two electrodes are of different metals, they cause an electrical current to flow via at least a portion of the user or the soil of the plant."],["1.A method for electrical stimulation therapy, the method comprising: attaching a first electrode to a soil of a plant at a first location, wherein the first electrode is substantially of a first metal or a first metal alloy, and wherein the first electrode is not connected to any electrical device; and attaching a second electrode to the soil of the plant at a second location, wherein the second electrode is substantially of a second metal or a second metal alloy, wherein the second electrode is not connected to any electrical device, wherein the first metal or the first metal alloy differs from the second metal or the second metal alloy, wherein the first location differs from the second location, and wherein the first electrode and the second electrode cause an electrical current to flow via at least a portion of the soil of the plant.","2.A system for electrical stimulation therapy, the system comprising: a first electrode being substantially of a first metal, wherein the first electrode is not connected to any electrical device; and a second electrode being substantially of a second metal, wherein the second electrode is not connected to any electrical device, wherein the first metal differs from the second metal, wherein when the first electrode and the second electrode are attached to a user or a soil of a plant, the first electrode and the second electrode cause an electrical current to flow via at least one portion of the user or the soil of the plant.","3.The system of claim 2, further comprising: a first wearable element, wherein the first wearable element includes the first electrode; and a second wearable element, wherein the second wearable element includes the second electrode; 4.The system of claim 3, wherein the first wearable element includes one of the following: a first bracelet, a first armband, a first leg band, a necklace, a first bandage; wherein the second wearable element includes one of the following: a second bracelet, a second armband, a second leg band, and a second bandage.","5.The system of claim 2, further comprising a flexible substrate, wherein flexible substrate includes the first electrode and the second electrode.","6.The system of claim 5, further comprising: a third electrode being substantially of the first metal, wherein the third electrode is not connected to any electrical device; a fourth electrode being substantially of the second metal, wherein the fourth electrode is not connected to any electrical device, wherein when the first electrode, the second electrode, the third electrode, and the fourth electrode are attached to the user or the soil of the plant, the first electrode, the second electrode, the third electrode, and the fourth electrode cause an electrical current to flow via at least one portion of the user or the soil of the plant; a flexible non-conducting substrate, wherein the flexible non-conducting substrate holds the first electrode, the second electrode, the third electrode, and the fourth electrode; and a binder for binding the flexible non-conducting substrate to a surface of the user or the soil of the plant such that the first electrode, the second electrode, the third electrode, and the fourth electrode directly contact the surface of the user or the soil of the plant."],[" BACKGROUND "],[" SUMMARY This section is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description section.","This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.","According to one aspect of the disclosure, there is provided a method for electrical stimulation therapy.","The method comprises the step of attaching a first electrode to a user at a first location, where the first electrode is made substantially of a first metal or metal alloy; and the first electrode is not connected to any electrical device.","The method further comprises the step of attaching a second electrode to the user at a second location, where the second electrode is made substantially of a second metal or metal alloy.","The second electrode is not connected to any electrical device.","The first metal or metal alloy differs from the second metal or metal alloy.","The first electrode and the second electrode cause an electrical current to flow through at least a portion of the user.","According to another aspect of the disclosure, there is provided a method for electrical stimulation therapy.","The method comprises the step of attaching a first electrode to a soil of a plant at a first location, where the first electrode is substantially made of a first metal or metal alloy; and the first electrode is not connected to any electrical device.","The method further comprises the step of attaching a second electrode to the soil of the plant at a second location, where the second electrode is made substantially of a second metal or metal alloy.","The second electrode is not connected to any electrical device.","The first metal or metal alloy differs from the second metal or metal alloy.","The first electrode and the second electrode cause an electrical current to flow through at least a portion of the user.","According to yet another aspect of the disclosure, there is provided a system for electrical stimulation therapy.","The system comprises a first electrode made substantially of a first metal, where the first electrode is not connected to any electrical device, and where a second electrode is made substantially of a second metal not connected to any electrical device, and where the first metal differs from the second metal.","When the first electrode and the second electrode are attached to a user or a soil of a plant, the first electrode and the second electrode cause an electrical current to flow through at least one portion of the user or the plant.","Additional objects, advantages, and novel features of the examples will be set forth in part in the description, which follows, and in part will become apparent to those skilled in the art upon examination of the following description and the accompanying drawings or may be learned by production or operation of the examples.","The objects and advantages of the concepts may be realized and attained by means of the methodologies, instrumentalities and combinations particularly pointed out in the appended claims."],["CROSS-REFERENCE TO RELATED APPLICATION This application is a divisional application of U.S. application Ser.","No.","15/279,442, entitled “SYSTEMS AND METHODS FOR ELECTROSTIMULATION THERAPY”, filed on Sep. 29, 2016.BACKGROUND Technical Field This disclosure generally relates to electrical stimulation therapy.","More specifically, this disclosure relates to systems and methods for electrical stimulation therapy where electrical current is generated by metal electrodes without using any electrical devices such for a voltage source or a current source.","Description of Related Art The approaches described in this section could be pursued, but are not necessarily approaches that have been previously conceived or pursued.","Therefore, unless otherwise indicated herein, the approaches described in this section are not prior art to the claims in this application and are not admitted to be prior art by inclusion in this section.","Electrical stimulation (also referred herein to as “electrostimulation”) is a therapeutic treatment that applies electrical stimulation in treating muscle spasms and pain, which can also be used in rehabilitation and preventive medicine, providing post-exercise recovery, and so forth.","Some electrical stimulation methods involve elicitation of muscle contraction by causing electrical impulses to go through a certain area of a user's body.","Other electrical stimulation methods, such as electrophoresis, involve generating an electromagnetic field or applying a direct electrical current to cause body fluids or drugs to move within the user's body.","Known electrical stimulation methods are based on the usage of electrical medical devices for producing electrical currents for applying to the user for treatment purposes.","These electrical medical devices are not only expensive, but also inconvenient to use, especially when the electrical stimulation therapy should be given to a user for a prolonged period.","Thus, advancements in electrical stimulation are desired.","SUMMARY This section is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description section.","This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.","According to one aspect of the disclosure, there is provided a method for electrical stimulation therapy.","The method comprises the step of attaching a first electrode to a user at a first location, where the first electrode is made substantially of a first metal or metal alloy; and the first electrode is not connected to any electrical device.","The method further comprises the step of attaching a second electrode to the user at a second location, where the second electrode is made substantially of a second metal or metal alloy.","The second electrode is not connected to any electrical device.","The first metal or metal alloy differs from the second metal or metal alloy.","The first electrode and the second electrode cause an electrical current to flow through at least a portion of the user.","According to another aspect of the disclosure, there is provided a method for electrical stimulation therapy.","The method comprises the step of attaching a first electrode to a soil of a plant at a first location, where the first electrode is substantially made of a first metal or metal alloy; and the first electrode is not connected to any electrical device.","The method further comprises the step of attaching a second electrode to the soil of the plant at a second location, where the second electrode is made substantially of a second metal or metal alloy.","The second electrode is not connected to any electrical device.","The first metal or metal alloy differs from the second metal or metal alloy.","The first electrode and the second electrode cause an electrical current to flow through at least a portion of the user.","According to yet another aspect of the disclosure, there is provided a system for electrical stimulation therapy.","The system comprises a first electrode made substantially of a first metal, where the first electrode is not connected to any electrical device, and where a second electrode is made substantially of a second metal not connected to any electrical device, and where the first metal differs from the second metal.","When the first electrode and the second electrode are attached to a user or a soil of a plant, the first electrode and the second electrode cause an electrical current to flow through at least one portion of the user or the plant.","Additional objects, advantages, and novel features of the examples will be set forth in part in the description, which follows, and in part will become apparent to those skilled in the art upon examination of the following description and the accompanying drawings or may be learned by production or operation of the examples.","The objects and advantages of the concepts may be realized and attained by means of the methodologies, instrumentalities and combinations particularly pointed out in the appended claims.","BRIEF DESCRIPTION OF THE DRAWINGS Embodiments are illustrated by way of example and not limitation in the figures of the accompanying drawings, in which like references indicate similar elements and in which: FIG.","1 shows a front view of a user wearing a system for electrostimulation according to one example embodiment; FIG.","2 shows a back view of a user using a system for electrostimulation according to another example embodiment; FIG.","3 shows a front view of a system for electrostimulation according to yet another example embodiment; FIG.","4 shows a side view of a wearable element of a system for electrostimulation according to one example embodiment; FIG.","5 shows a side view of a wearable element of a system for electrostimulation according to yet another example embodiment; FIG.","6 shows a front view of a system for electrostimulation according to yet another example embodiment; FIG.","7 shows a front view of a system for electrostimulation according to yet another example embodiment; FIG.","8 shows a front view of a system for electrostimulation according to yet another example embodiment; and FIG.","9 is a process flow diagram showing a method for electrostimulation according to an example embodiment.","DETAILED DESCRIPTION OF EXAMPLE EMBODIMENTS The present teachings generally relate to systems and methods for electrical stimulation of any living object, including any tissue or fluid of a human, an animal, a plant, or any other natural object.","The electrical stimulation is provided or caused by applying at least two electrodes to a live object or soil of a plant, where the electrodes are substantially of different metals or different metal alloys, and not connected to any electrical device such a voltage or current source.","Most of tissues in a living object (e.g., a human, animal, or plant) include various liquids, such as water, a solution of water, or other liquids infused with salts, minerals, solvents, or other elements.","It was found that the liquids or tissue of living objects can serve as an electrolyte or an electrically conducting solution.","The two or more electrodes, when in contact with the living object or its fluids, create a difference in potentials between the electrodes without using any electrical current or voltage sources.","The difference in potentials causes electrons to flow in the living object from one of the electrodes to another, while holes/ions can flow in the living object in the opposite direction.","In this sense, one of the electrode can be considered as a cathode, while another electrode can be considered as an anode.","The difference in potentials can be created only when the electrodes are of different metals or metal alloys.","According to the present teachings, the electrodes can produce a difference of electric potential in a range from about 0.1 volts to about 1.4 volts, while the electrical current flowing from one electrode to another can be in a range from about 0.1 microampere to about 1,400 microampere.","These ranges of voltages and electrical currents appear to be safe for humans and most of the animals and plants.","The electrodes can be applied to or mounted on the living object or the soil of the pant at any distance therebetween (e.g., from one millimeter to two meters or even more) and still provide the difference in potentials.","The inventors found that an electrical current will be caused by the electrodes when they are placed or attached to a living object at any distance therebetween.","The electrostimulation therapy with the electrodes of this disclosure can be conveniently performed for long periods of time, ranging from about 1 hour to 24 hours or even more.","The methods for electrostimulation of this disclosure can be used to treat many disorders of people, animals, and other living objects, including plants.","For example, the present methods for electrostimulation can be used to treat infections, viral disorders, bacterial disorders, and reduce pain.","It was unexpectedly found that the methods for electrostimulation can deactivate viruses and bacteria without harming normal tissues.","Thus, the methods for electrostimulation may treat or assist in treating Acquired ImmunoDeficiency Syndrome (AIDS) or Human ImmunoDeficiency Virus (HIV) disorders.","The electrostimulation can be also helpful or assisting in treating some or all cancers.","In addition, the inventors found that the present teachings can be helpful in treating the following human disorders or conditions: urinary incontinence, enlarged prostate, arthritis, back pain, diabetic ulcers, fibromyalgia, headaches, herpes, neck pain, neuropathy, sciatica, shingles, sports injuries, tendon and ligament pain, rheumatism, carpal tunnel syndrome, inflammatory arthritis, fighting infectious diseases, viral infections, migraines, capsulitis, synovitis, disc diseases, stroke, tendonitis, bursitis, intractable pain, torticollis, soft tissue, bell's palsy, surgical incision, abdominal cramps, edema, whiplash, postop healing, injury, myofascial pain, chronic pain, temporomandibular joint dysfunction, sinus problems, acute pain, decubitus, myositis, facial lifting, skin rejuvenation, hypertension, macular degeneration, major depression, essential tremor, micro current deep brain stimulation, obsessive-compulsive disorder, Parkinson's disease, Alzheimer's disease, and so forth.","The present teachings can be also helpful in improving well-being, and providing physiotherapy, anti-aging, and cosmetic treatments, among others.","Notably, the present teachings do not require usage of any additional electrolytic solution or conductive gel to be placed between the electrodes and the living object.","No reservoirs with a reducing agent and no reservoirs with an oxidizing agent are needed between the electrodes and the living object according to embodiments of this disclosure.","Moreover, the present teachings of electrostimulation should not be used and should not be applied directly on wounds.","The inventors of the present methods for electrostimulation suggest the following explanation of why these methods help in treating disorders and improving general well-being of living objects.","Each tissue type in a body of a human and many animals has its own signature electrical frequency, which may be disrupted by an injury or a disease.","The electrostimulation therapy according to the embodiments of this disclosure restores normal frequencies within human cells, resulting in remarkable improvements in treating pain, inflammation, and restoring a function of the cells.","At the cellular level, the electrostimulation therapy stimulates a dramatic increase in adenosine triphosphate (ATP), the energy that fuels all biochemical functions in a human body.","It also bumps up protein synthesis, which is necessary for tissue repair.","The ensuing enhancement in blood flow and decrease in inflammation translates into reductions in pain and muscle spasms, as well as increased range of motion.","The following detailed description of embodiments includes references to the accompanying drawings, which form a part of the detailed description.","Approaches described in this section are not prior art to the claims and are not admitted to be prior art by inclusion in this section.","The drawings show illustrations in accordance with example embodiments.","These example embodiments, which are also referred to herein as “examples,” are described in enough detail to enable those skilled in the art to practice the present subject matter.","The embodiments can be combined, other embodiments can be utilized, or structural, logical and operational changes can be made without departing from the scope of what is claimed.","The following detailed description is, therefore, not to be taken in a limiting sense, and the scope is defined by the appended claims and their equivalents.","For purposes of this patent document, the terms “or” and “and” shall mean “and/or” unless stated otherwise or clearly intended otherwise by the context of their use.","The term “a” shall mean “one or more” unless stated otherwise or where the use of “one or more” is clearly inappropriate.","The terms “comprise,” “comprising,” “include,” and “including” are interchangeable and not intended to be limiting.","For example, the term “including” shall be interpreted to mean “including, but not limited to.” Additionally, all ranges provided herein include the upper and lower values of the range unless explicitly noted.","For example, the term “about” shall mean a reasonable deviation of a value accompanying this term.","If it is not specified otherwise, the term “about” may refer to a variation of 20% from an indicated value.","In the case of a range of values, the term “about” may refer to a 20% variation from both the lower and upper limits of the range.","Moreover, it shall be understood that when an element is referred to as being “on” or “connected” or “coupled” to another element, it can be directly on or connected or coupled to the other element or intervening elements can be present.","In contrast, when an element is referred to as being “directly on” or “directly connected” or “directly coupled” to another element, there are no intervening elements present.","Other words used to describe the relationship between elements should be interpreted in a like fashion (e.g., “between” versus “directly between,” “adjacent” versus “directly adjacent,” and so forth).","Spatially relative terms, such as “beneath,” “below,” “lower,” “above,” “upper” and the like may be used to describe an element or feature's relationship to another element(s) and/or feature(s) as, for example, illustrated in the drawings.","It shall be appreciated the spatially relative terms are intended to encompass different orientations of system for electrostimulation or its elements in use in addition to the orientation depicted in the figures.","For example, if the system for electrostimulation or any of its components in the drawings is turned over, elements described as “below” and/or “beneath” other elements or features would then be oriented “above” the other elements or features.","The system for electrostimulation or its components may be otherwise oriented (e.g., rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly.","The term “user” shall be construed to mean any individual, human, animal, or any other living object, using the system for electrostimulation according to any embodiment described herein.","The term “user” shall also encompass a patient, client, customer, and the like.","In some embodiments, the term “user” can be construed to mean a plant.","The term “electrostimulation” shall be construed to mean a process for creating, producing, applying, or providing an electrical current in any tissue or liquid of any living object such as a human, animal, or plant.","The terms “electrostimulation” and “electrical stimulation” can be used interchangeably.","The term “electrode” shall be construed to mean any electric conductor of any shape or design.","The electrode can be made of a metal or metal alloy.","Each of the electrodes can be made as a single whole, although other implementations are also possible and within the scope of this disclosure.","In certain embodiments of this disclosure, the electrodes have one or more homogeneous (solid, smooth) surfaces without any substantial irregularities.","Now, exemplary embodiments are described with reference to the drawings.","The drawings are schematic illustrations of idealized example embodiments.","As such, variations from the shapes of the illustrations as a result, for example, of manufacturing techniques or tolerances, are to be expected.","Thus, example embodiments discussed herein should not be construed as limited to the particular shapes of regions illustrated herein but are to include deviations in shapes that result, for example, from manufacturing.","FIG.","1 shows a front view of a user 100 wearing a system 110 for electrostimulation according to one example embodiment.","The system 110 for electrostimulation includes two or more electrodes, where at least one of the electrodes is made of a metal or metal alloy that is different from other electrodes.","In this example, the system 110 for electrostimulation includes two electrodes 110a and 110b, where the electrode 110a is made substantially of one metal, while the electrode 110b is made substantially of another metal.","The metals for the electrodes of the system 110 can be selected from a wide range of different metals, including, for example, aluminum (Al), gold (Au), iron (Fe), copper (Cu), zinc (Zn), palladium (Pa), magnesium (Mg), platinum (Pl), silver (Ag), titanium (Ti), tungsten (W), and any alloys thereof.","The electrodes 110aand 110b can also be made of various alloys containing chromium (Cr) that are used to make stainless steel.","Thus, stainless steel (of any grade) can be used to make electrodes.","In other words, the disclosed technology can utilize potential difference between various metals as well as various metal alloys.","As discussed above, when the electrodes 110a and 110b are of different metals (or metal alloys), they produce a difference of electric potential in a range from about 0.1 volts to about 1.4 volts, while the electrical current flowing from one electrode to another can be in a range from about 1 microampere to about 1,400 microampere.","The following table provides approximate differences of electric potential that are produced by different metal pairs: TABLE 1 Second Voltage (difference of Electrode potential), approximate values, First Electrode 110a 110b error can be up to 20% Al Au 0.7 volt Au Fe 0.04 volt Al Fe 0.6 volt Au Cu 0.01 volt Cu Fe 0.06 volt Au Zn 0.85 volt Zn Fe 0.9 volt Zn Cu 0.8 volt Zn Al 0.2 volt Al Pd 0.65 volt Au Pd Less than 0.01 volt Cu Pd 0.12 volt Fe Pd 0.04 volt Zn Pd 0.8 volt Al Ag 0.65 volt Au Ag 0.01 volt PD Ag 0.01 volt Cu Ag 0.15 volt Fe Ag 0.02 volt Zn Ag 0.85 volt Al Pl 0.6 volt Pl Pd Less than 0.01 volt Pl Au Less than 0.01 volt Pl Ag Less than 0.01 volt Cu Pl 0.08 volt Fe Pl 0.01 volt Zn Pl 0.7 volt Mg Zn 0.65 volt Mg Fe 1.3 volt Mg Cu 1.1 volt Mg Al 0.7 volt Mg Pl 1.2 volt Mg Au 1.4 volt Mg Pd 1.2 volt Mg Ag 1.2 volt Table 1 is applicable to all embodiments of this disclosure.","Some example metal pairs for the electrodes 110a, 110b can be as follows.","When the first electrode 110a is substantially of silver and the second electrode 110b is substantially of zinc, the difference of potential can be about 850 millivolts when the electrodes 110a, 110b are applied to a human body.","When the first electrode 110a is substantially of iron and the second electrode 110b is substantially of zinc, the difference of potential can be about 900 millivolts when the electrodes 110a, 110b are applied to a human body.","The electrical current between the electrodes 110a, 110b can vary and be in a range from about 1 microampere to about 1,400 microampere.","It is important to mention that the electrodes 110a, 110b are not electrically or operatively connected to any medical device, including a voltage source or a current source.","In some embodiments, however, the electrodes 110a, 110b can be electrically connected with one another to make a closed circuit (e.g., through any living tissue).","Referring back to FIG.","1, the electrodes 110a, 110b can be made in the form of a wearable item such as a bracelet, wristband, armband, leg band, necklace, or any piece of jewelry.","The electrodes 110a, 110b can be placed, fixed, attached, secured, or provided at any location of the human body, animal, plant, or soil of the plant.","For example, as shown in FIG.","1, the first electrode 110a being in the form of a first bracelet, is provided on the right wrist of the user 100, and the second electrode 110b being in the form of a second bracelet, is provided on the left wrist of the user 100.The electrodes 110a, 110b can be provided in other forms too.","For example, the electrodes can be attached to or provided by a skin patch, adhesive bandage, spray metal paint, topical, transdermal, intradermal, subcutaneous, intramuscular, intravenous, or other forms.","The electrodes 110a, 110b can be also of different designs or shapes.","For example, the electrodes 110a, 110b can be in the form of needles, discs, plates, panels, metal meshes, nanowires, metal dots, and the like.","The distance between the electrodes 110a, 110b can be in a range from 10 millimeters to 2 meters or even more.","The dimensions of the electrodes 110a, 110b can vary in any reasonable range.","For example, the surface area of the electrodes 110a, 110b that are in contact with the user (or other living object) can be from about 1 square millimeter to about 200 square centimeter.","FIG.","2 shows a back view of a user 100 using a system 110 for electrostimulation according to another example embodiment.","Here, system 110 for electrostimulation includes a plurality of electrodes 110a, 110b, 110c, 110d, 110e, 110f, 110g, and 110h.","The number of electrodes is not limited to eight (like in this embodiment) and, generally, can be two or more electrodes.","In this embodiment, the electrodes 110a, 110b, 110c, 110d, 110e, 110f, 110g, and 110h are in the form of acupuncture needles that are inserted into the user's skin.","In one example, the electrode 110a is made of metal A, while other electrodes 110b-110h can be made of metal B.","In another example, the electrodes 110a, 110b are made of metal A, while other electrodes 110c-110h can be made of metal B.","In yet another example, the electrodes 110a, 110b, 110c are made of metal A, while other electrodes 110d-110h can be made of metal B.","In yet another example, the electrodes 110a-110d are made of metal A, while other electrodes 110e-110h can be made of metal B.","In yet another example, the electrodes 110a, 110c, 110e, 110g are made of metal A, while the electrodes 110b, 110d, 110f, 110h are made of metal B.","In other example embodiments, the electrodes 110a-110h can be made of more than two different metals.","For example, the electrode 110a is made of metal A, the electrode 110b is made of metal B, while other electrodes 110c-110h are made of metal C. In another example, the electrode 110a is made of metal A, the electrode 110b is made of metal B, the electrode 110c is made of metal C, while other electrodes 110d-110h are made of metal D. Any other combinations can be also used, but their description is not given in this document.","FIG.","3 shows a front view of a system 300 for electrostimulation according to yet another example embodiment.","The system 300 for electrostimulation includes at least two separate wearable elements 300a and 300b.","The wearable elements 300a and 300b can refer to a patch or a bandage.","The wearable elements 300a, 300b include substrates 310a, 310b, respectively.","The substrates 310a, 310b can be flexible substrates that are not electrically conductive.","For example, each of the substrates 310a, 310b can include a pliable base, such as a medical grade 100% polyester fabric material; however, other materials can be also used such as gauze, mesh, fabric, polymer base, or other materials as long as they are pliable.","Each of the substrates 310a, 310b includes a binder 320a, 320b, respectively, for releasable binding to a surface or skin of a living object (e.g., a human or animal).","The binder 320a, 320b can be made of non-electrically conductive material such as a polymer or any other suitable medium used in certain coating, laminating, or adhesion techniques.","Each of the substrates 310a, 310b also includes an electrode 110a, 110b, respectively.","As discussed above, the electrodes 110a, 110b are of different metals or metal alloys.","The electrodes 110a, 110b can be in the form of a metal plate, puck, disc, sphere, mesh, coating (e.g., a silver nanowire layer), film, layer, and the like.","In certain embodiments, the wearable elements 300a and 300b are removably attached to a surface or skin of living object at a distance ranging from about 10 millimeters to about 2 meters or even more.","The wearable elements 300a, 300b can remain attached to the surface or skin of living object for a period of at least one minute or more.","In certain embodiments, there can be provided additional wearable elements similar to the wearable elements 300a, 300b.","The number of such wearable elements is not limited.","FIG.","4 shows a side view of a wearable element 400 of a system for electrostimulation according to one example embodiment.","The wearable element 400 can be an instant of wearable element 300a or 330b shown in FIG.","3.The wearable element 400 includes a flexible substrate 310, a binder 320 in the form of polymeric adhesive layer, and an electrode 110.The electrode 110 is secured on a surface of the flexible substrate 310.The binder 320 is provided on the same surface of the flexible substrate 310 substantially around the electrode 110.When the wearable element 400 is in contact with a surface or skin 410 of a living object, the binder 320 provides adhesive connection of the entire wearable element 400 for a long period of time such that the electrode 110 directly contacts the surface or skin 410 of the living object.","FIG.","5 shows a side view of a wearable element 500 of a system for electrostimulation according to yet another example embodiment.","The wearable element 500 can be an instant of wearable element 300a or 330b shown in FIG.","3.The wearable element 500 includes a flexible substrate 310, a binder 320, for example, in the form of a polymeric adhesive layer, and an electrode 110.The binder 320 can exhibit electroconducting properties only when 320 is made of a non-conductive absorbing material and soaked in an electrolyte.","In some example embodiments, the electrolyte can be substituted by tap water (rich with minerals).","The bottom surface of electrode 110 is secured on the top surface of the flexible substrate 310.The bottom of the binder 320 is provided on the top surface of the electrode 110 and optionally on the top surface of the flexible substrate 310 where there is no electrode 110.When the wearable element 500 is in contact with the surface or skin 410 of the living object, the binder 320 provides adhesive connection of the entire wearable element 500 such that the electrode 110 indirectly contacts the surface or skin 410 of the living object.","FIG.","6 shows a front view of a system 600 for electrostimulation according to yet another example embodiment.","Generally, the system 600 for electrostimulation can be a single wearable element such as a patch or a bandage.","The system 600 includes a substrate 310, which can be of a non-electrically conductive, but flexible material.","For example, the substrate 310 can include a pliable base, such as a medical grade 100% polyester fabric material; however, other materials can be also used such as gauze, mesh, fabric, polymer base, or other materials as long as they are pliable.","The substrate 310 includes a binder 320 for releasable binding the entire system 600 to a surface or skin of a living object (e.g., a human, or animal).","The binder 320 can be made of non-electrically conductive material such as a polymer or any other suitable medium used in certain coating, laminating, or adhesion techniques.","The substrate 310 also includes two or more electrodes such as electrodes 110a, 110b.","As discussed above, the electrodes 110a, 110b are of different metals or metal alloys.","The electrodes 110a, 110b can be in the form of a metal plate, puck, disc, sphere, mesh, coating (e.g., a silver nanowire layer), film, layer, and the like.","FIG.","7 shows a front view of a system 700 for electrostimulation according to yet another example embodiment.","The system 700 for electrostimulation can be directed to a single wearable element such as a patch or a bandage.","The system 700 includes a substrate 310, which can be of a non-electrically conductive, but flexible material.","For example, the substrate 310 can include a pliable base, such as a medical grade 100% polyester fabric material; however, other materials can be also used such as gauze, mesh, fabric, polymer base, or other materials as long as they are pliable.","The substrate 310 includes a binder 320 for releasable binding the entire system 700 to a surface or skin of a living object (e.g., a human, or animal).","The binder 320 can be made of non-electrically conductive material such as a polymer or any other suitable medium used in certain coating, laminating, or adhesion techniques.","The substrate 310 also includes four or more electrodes such as electrodes 110a, 110b, 110c, and 110d.","The electrodes 110a, 110b, 110c, and 110d can be in the form of a metal plate, puck, disc, sphere, mesh, coating (e.g., a silver nanowire layer), film, layer, and the like.","As discussed above, the electrodes 110a, 110b, 110c, and 110d are of at least two different metals or metal alloys.","For example, the electrode 110a is made of metal A, and the electrodes 110b, 110c, 110d are made of metal B.","In another example, the electrode 110b is made of metal A, and the electrodes 110a, 110c, 110d are made of metal B.","In yet another example, the electrode 110c is made of metal A, and the electrodes 110a, 110b, 110d are made of metal B.","In yet another example, the electrode 110d is made of metal A, and the electrodes 110a, 110b, 110c are made of metal B.","In yet another example, the electrodes 110a and 110b are made of metal A, and the electrodes 110c and 110d are made of metal B.","In yet another example, the electrodes 110a and 110c are made of metal A, and the electrodes 110b and 110d are made of metal B.","In yet another example, the electrode 110a is made of metal A, the electrode 110b is made of metal B, and the electrodes 110c and 110d are made of metal C. In yet another example, the electrode 110a is made of metal A, the electrode 110b is made of metal B, the electrode 110c is made of metal C, and the electrode 110d is made of metal D. Each of the metals A, B, C, and D can be selected from a group, comprising, for example, the following metals: aluminum (Al), gold (Au), iron (Fe), copper (Cu), zinc (Zn), palladium (Pa), magnesium (Mg), platinum (Pl), silver (Ag), and any alloy thereof.","FIG.","8 shows a front view of a system 800 for electrostimulation according to yet another example embodiment.","The system 800 for electrostimulation can be directed to a single wearable element such as a patch or a bandage.","The system 800 includes a substrate 310, which can be of a non-electrically conductive, but flexible material.","For example, the substrate 310 can include a pliable base, such as a medical grade 100% polyester fabric material; however, other materials can be also used such as gauze, mesh, fabric, polymer base, or other materials as long as they are pliable.","The substrate 310 includes a binder 320 for releasable binding the entire system 800 to a surface or skin of a living object (e.g., a human or animal).","The binder 320 can be made of non-electrically conductive material such as a polymer or any other suitable medium used in certain coating, laminating, or adhesion techniques.","The substrate 310 also includes four or more electrodes such as electrodes 110a, 110b, 110c, and 110d.","The electrodes 110a, 110b, 110c, and 110d can be in the form of a metal plate, puck, disc, spheres, semi-spheres, mesh, coating (e.g., a silver nanowire layer), film, layer, and the like.","As discussed above, the electrodes 110a, 110b, 110c, and 110d are made up of two different metals or different metal alloys.","For example, the electrode 110a is made of metal A, and the electrode 110b is made of metal B, the electrode 110c is made of metal A, and the electrode 110d is made of metal B.","Each of the metals of the electrodes 110a, 110b, 110c, and 110d can be selected from a group, comprising, for example, the following metals: aluminum (Al), gold (Au), iron (Fe), copper (Cu), zinc (Zn), palladium (Pa), magnesium (Mg), platinum (Pl), silver (Ag), and so forth.","When electrodes 110a, 110b, 110c, and 110d are arranged in series, the output voltage for electrostimulation therapy can be increased up to a desired value, provided there can be any other suitable number of electrodes 110a, 110b, 110c, and 110d.","Still referring to FIG.","8, there can be provided electrolyte layers 810a, 810b, 810c between the electrodes 110a-110d, respectively, as shown in the figure.","The electrolyte layers 810a-810c can be of any suitable non-conductive absorbing materials.","The embodiment shown in FIG.","8 illustrates how the difference of potentials created by the electrodes can be increased up to several voltages; however, in order for the system 800 to operate efficiently, the two end electrodes 110a and 110d must be placed, arranged, fixed, or attached onto the skin of the user: human or animal.","The rest of the elements of system 800, in particular, the electrolyte layer 810a, the electrode 110b, the electrolyte layer 810b, the electrode 110c, and the electrolyte layer 810c should not meet the skin of the user.","The electrodes 110a-110d are electrically interconnected in series using the electrolyte layers 810a-810c.","In this case, the output voltage of the system 800 will be equal to a sum of the voltages generated by pairs of the electrodes 110a-110b, 110b-110c, and 110c-110d.","FIG.","9 is a process flow diagram showing a method 900 for electrostimulation according to an example embodiment.","The method 900 may have additional steps not shown herein, but which can be evident for those skilled in the art from the present disclosure.","The method 900 may also have fewer steps than outlined below.","At step 905, a first electrode 110a is attached, fixed, inserted, or provided to a user (human or animal) or soil of a plant at a first location.","For these ends, a first wearable element can be provided that includes the first electrode 110a.","The first wearable element can be placed, arranged, fixed, attached, or otherwise provided to the user or plant such that the first electrode 110a is in contact with a tissue or liquid of the user or plant.","In some embodiments, the first electrode 110a can be inserted into skin of the user (e.g., when the electrodes are in the form of a needle).","In some embodiments, the first electrode 110a can be inserted into a blood vessel, vein, or arteria of the user in the form of a needle to provide electrostimulation therapy of blood or other fluids.","At step 910, a second electrode 110b is attached, fixed, inserted, or provided to the user (human or animal) or the soil of the plant at a second location.","For these ends, a second wearable element can be provided that includes the second electrode 110b.","The second wearable element can be placed, arranged, fixed, attached, or otherwise provided to the user or soil of the plant such that the second electrode 110b is in contact with a tissue or liquid of the user or the soil of the plant.","In some embodiments, the second electrode 110b can be inserted into skin of the user in the form of a needle.","In some embodiments, the second electrode 110b can be inserted into a blood vessel, vein, or arteria of the user in the form of a needle to provide electrostimulation therapy of blood or other fluids.","The first wearable element includes one of the following: a first bracelet, a first armband, a first leg band, and a necklace; however, the second wearable element can include one of the following: a second bracelet, a second armband, and a second leg band.","The wearable elements can also refer to pieces of jewelry.","It should be noted, however, that in other embodiments, wearable elements are not necessary.","For example, each of the first electrode 110a and the second electrode 110b is included in an acupuncture needle.","Thus, the operation of attachment of the first electrode to the user or the soil of the plant can include inserting the first electrode 110a through skin of the user or inserting in the soil of the plant; similarly, the operation of attachment of the second electrode 110b to the user or the soil of the plant includes inserting the second electrode 110b through skin of the user.","As discussed above, the first electrode 110a is substantially of a first metal, while the second electrode 110b is substantially of a second metal, which differs from the first metal.","Moreover, none of the electrodes is connected to any electrical device.","In addition, the first location differs from the second location.","After the first electrode and the second electrode are in contact with the user or the soil of the plant, they cause an electrical current to flow via at least a portion of the user or the soil of the plant.","At optional step 915, one or more additional electrodes (similar to electrodes 110a, 110b) can be attached, fixed, inserted, or provided to the user (human or animal) or the soil of the plant at additional locations.","Similar to above, one or more additional wearable elements can be provided such that any of the additional electrodes is in contact with the tissue or liquid of the user or the soil of the plant.","In some embodiments, the additional electrodes can be inserted into skin of the user or inserted into a blood vessel, vein, or arteria of the user to provide electrostimulation therapy of blood or other fluids.","At step 920, the first electrode 110a, the second electrode 110b, and all other additional electrodes (if any) are maintained at their locations of the user or the soil of the plant for a predetermined period.","The predetermined period can be in a range from about 1 hour to about 24 hours or more, during which electrostimulation therapy is provided.","The electrostimulation therapy involves generation of the electrical current by the electrodes 110a, 110b, etc.","in a range from about 0.1 microampere to about 1,400 microampere.","At step 925, the first electrode 110a, the second electrode 110b, and all other additional electrodes (if any) are removed from the user or the soil of the plant after the predetermined period is elapsed.","As discussed above, the method 900 for electrostimulation can treat various disorders or conditions of people, animals, and improve growth of the plants.","Thus, the systems and methods for electrostimulation have been described.","Although embodiments have been described with reference to specific example embodiments, it will be evident that various modifications and changes can be made to these example embodiments without departing from the broader spirit and scope of the present application.","Accordingly, the specification and drawings are to be regarded in an illustrative rather than a restrictive sense."]],"string":"[\n [\n \"SYSTEMS AND METHODS FOR ELECTROSTIMULATION THERAPY\",\n \"A system for electrostimulation therapy includes two or more electrodes of different metals or metal alloys.\",\n \"The electrodes can be optionally provided on a flexible non-conducting substrate with a binder, thereby acting as a bandage or patch.\",\n \"Alternatively, the electrodes can be in the form of a needle, such as acupuncture needle, bracelets, armbands, wristbands, necklaces, or jewelry pieces.\",\n \"A method for electrostimulation therapy includes the steps of attaching a first electrode to a user or soil of a plant at a first location and attaching at least one additional electrode to the user or the plant at other locations for a predetermined period.\",\n \"The electrodes are not connected to a voltage or current source.\",\n \"Because at least two electrodes are of different metals, they cause an electrical current to flow via at least a portion of the user or the soil of the plant.\"\n ],\n [\n \"1.A method for electrical stimulation therapy, the method comprising: attaching a first electrode to a soil of a plant at a first location, wherein the first electrode is substantially of a first metal or a first metal alloy, and wherein the first electrode is not connected to any electrical device; and attaching a second electrode to the soil of the plant at a second location, wherein the second electrode is substantially of a second metal or a second metal alloy, wherein the second electrode is not connected to any electrical device, wherein the first metal or the first metal alloy differs from the second metal or the second metal alloy, wherein the first location differs from the second location, and wherein the first electrode and the second electrode cause an electrical current to flow via at least a portion of the soil of the plant.\",\n \"2.A system for electrical stimulation therapy, the system comprising: a first electrode being substantially of a first metal, wherein the first electrode is not connected to any electrical device; and a second electrode being substantially of a second metal, wherein the second electrode is not connected to any electrical device, wherein the first metal differs from the second metal, wherein when the first electrode and the second electrode are attached to a user or a soil of a plant, the first electrode and the second electrode cause an electrical current to flow via at least one portion of the user or the soil of the plant.\",\n \"3.The system of claim 2, further comprising: a first wearable element, wherein the first wearable element includes the first electrode; and a second wearable element, wherein the second wearable element includes the second electrode; 4.The system of claim 3, wherein the first wearable element includes one of the following: a first bracelet, a first armband, a first leg band, a necklace, a first bandage; wherein the second wearable element includes one of the following: a second bracelet, a second armband, a second leg band, and a second bandage.\",\n \"5.The system of claim 2, further comprising a flexible substrate, wherein flexible substrate includes the first electrode and the second electrode.\",\n \"6.The system of claim 5, further comprising: a third electrode being substantially of the first metal, wherein the third electrode is not connected to any electrical device; a fourth electrode being substantially of the second metal, wherein the fourth electrode is not connected to any electrical device, wherein when the first electrode, the second electrode, the third electrode, and the fourth electrode are attached to the user or the soil of the plant, the first electrode, the second electrode, the third electrode, and the fourth electrode cause an electrical current to flow via at least one portion of the user or the soil of the plant; a flexible non-conducting substrate, wherein the flexible non-conducting substrate holds the first electrode, the second electrode, the third electrode, and the fourth electrode; and a binder for binding the flexible non-conducting substrate to a surface of the user or the soil of the plant such that the first electrode, the second electrode, the third electrode, and the fourth electrode directly contact the surface of the user or the soil of the plant.\"\n ],\n [\n \" BACKGROUND \"\n ],\n [\n \" SUMMARY This section is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description section.\",\n \"This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.\",\n \"According to one aspect of the disclosure, there is provided a method for electrical stimulation therapy.\",\n \"The method comprises the step of attaching a first electrode to a user at a first location, where the first electrode is made substantially of a first metal or metal alloy; and the first electrode is not connected to any electrical device.\",\n \"The method further comprises the step of attaching a second electrode to the user at a second location, where the second electrode is made substantially of a second metal or metal alloy.\",\n \"The second electrode is not connected to any electrical device.\",\n \"The first metal or metal alloy differs from the second metal or metal alloy.\",\n \"The first electrode and the second electrode cause an electrical current to flow through at least a portion of the user.\",\n \"According to another aspect of the disclosure, there is provided a method for electrical stimulation therapy.\",\n \"The method comprises the step of attaching a first electrode to a soil of a plant at a first location, where the first electrode is substantially made of a first metal or metal alloy; and the first electrode is not connected to any electrical device.\",\n \"The method further comprises the step of attaching a second electrode to the soil of the plant at a second location, where the second electrode is made substantially of a second metal or metal alloy.\",\n \"The second electrode is not connected to any electrical device.\",\n \"The first metal or metal alloy differs from the second metal or metal alloy.\",\n \"The first electrode and the second electrode cause an electrical current to flow through at least a portion of the user.\",\n \"According to yet another aspect of the disclosure, there is provided a system for electrical stimulation therapy.\",\n \"The system comprises a first electrode made substantially of a first metal, where the first electrode is not connected to any electrical device, and where a second electrode is made substantially of a second metal not connected to any electrical device, and where the first metal differs from the second metal.\",\n \"When the first electrode and the second electrode are attached to a user or a soil of a plant, the first electrode and the second electrode cause an electrical current to flow through at least one portion of the user or the plant.\",\n \"Additional objects, advantages, and novel features of the examples will be set forth in part in the description, which follows, and in part will become apparent to those skilled in the art upon examination of the following description and the accompanying drawings or may be learned by production or operation of the examples.\",\n \"The objects and advantages of the concepts may be realized and attained by means of the methodologies, instrumentalities and combinations particularly pointed out in the appended claims.\"\n ],\n [\n \"CROSS-REFERENCE TO RELATED APPLICATION This application is a divisional application of U.S. application Ser.\",\n \"No.\",\n \"15/279,442, entitled “SYSTEMS AND METHODS FOR ELECTROSTIMULATION THERAPY”, filed on Sep. 29, 2016.BACKGROUND Technical Field This disclosure generally relates to electrical stimulation therapy.\",\n \"More specifically, this disclosure relates to systems and methods for electrical stimulation therapy where electrical current is generated by metal electrodes without using any electrical devices such for a voltage source or a current source.\",\n \"Description of Related Art The approaches described in this section could be pursued, but are not necessarily approaches that have been previously conceived or pursued.\",\n \"Therefore, unless otherwise indicated herein, the approaches described in this section are not prior art to the claims in this application and are not admitted to be prior art by inclusion in this section.\",\n \"Electrical stimulation (also referred herein to as “electrostimulation”) is a therapeutic treatment that applies electrical stimulation in treating muscle spasms and pain, which can also be used in rehabilitation and preventive medicine, providing post-exercise recovery, and so forth.\",\n \"Some electrical stimulation methods involve elicitation of muscle contraction by causing electrical impulses to go through a certain area of a user's body.\",\n \"Other electrical stimulation methods, such as electrophoresis, involve generating an electromagnetic field or applying a direct electrical current to cause body fluids or drugs to move within the user's body.\",\n \"Known electrical stimulation methods are based on the usage of electrical medical devices for producing electrical currents for applying to the user for treatment purposes.\",\n \"These electrical medical devices are not only expensive, but also inconvenient to use, especially when the electrical stimulation therapy should be given to a user for a prolonged period.\",\n \"Thus, advancements in electrical stimulation are desired.\",\n \"SUMMARY This section is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description section.\",\n \"This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.\",\n \"According to one aspect of the disclosure, there is provided a method for electrical stimulation therapy.\",\n \"The method comprises the step of attaching a first electrode to a user at a first location, where the first electrode is made substantially of a first metal or metal alloy; and the first electrode is not connected to any electrical device.\",\n \"The method further comprises the step of attaching a second electrode to the user at a second location, where the second electrode is made substantially of a second metal or metal alloy.\",\n \"The second electrode is not connected to any electrical device.\",\n \"The first metal or metal alloy differs from the second metal or metal alloy.\",\n \"The first electrode and the second electrode cause an electrical current to flow through at least a portion of the user.\",\n \"According to another aspect of the disclosure, there is provided a method for electrical stimulation therapy.\",\n \"The method comprises the step of attaching a first electrode to a soil of a plant at a first location, where the first electrode is substantially made of a first metal or metal alloy; and the first electrode is not connected to any electrical device.\",\n \"The method further comprises the step of attaching a second electrode to the soil of the plant at a second location, where the second electrode is made substantially of a second metal or metal alloy.\",\n \"The second electrode is not connected to any electrical device.\",\n \"The first metal or metal alloy differs from the second metal or metal alloy.\",\n \"The first electrode and the second electrode cause an electrical current to flow through at least a portion of the user.\",\n \"According to yet another aspect of the disclosure, there is provided a system for electrical stimulation therapy.\",\n \"The system comprises a first electrode made substantially of a first metal, where the first electrode is not connected to any electrical device, and where a second electrode is made substantially of a second metal not connected to any electrical device, and where the first metal differs from the second metal.\",\n \"When the first electrode and the second electrode are attached to a user or a soil of a plant, the first electrode and the second electrode cause an electrical current to flow through at least one portion of the user or the plant.\",\n \"Additional objects, advantages, and novel features of the examples will be set forth in part in the description, which follows, and in part will become apparent to those skilled in the art upon examination of the following description and the accompanying drawings or may be learned by production or operation of the examples.\",\n \"The objects and advantages of the concepts may be realized and attained by means of the methodologies, instrumentalities and combinations particularly pointed out in the appended claims.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS Embodiments are illustrated by way of example and not limitation in the figures of the accompanying drawings, in which like references indicate similar elements and in which: FIG.\",\n \"1 shows a front view of a user wearing a system for electrostimulation according to one example embodiment; FIG.\",\n \"2 shows a back view of a user using a system for electrostimulation according to another example embodiment; FIG.\",\n \"3 shows a front view of a system for electrostimulation according to yet another example embodiment; FIG.\",\n \"4 shows a side view of a wearable element of a system for electrostimulation according to one example embodiment; FIG.\",\n \"5 shows a side view of a wearable element of a system for electrostimulation according to yet another example embodiment; FIG.\",\n \"6 shows a front view of a system for electrostimulation according to yet another example embodiment; FIG.\",\n \"7 shows a front view of a system for electrostimulation according to yet another example embodiment; FIG.\",\n \"8 shows a front view of a system for electrostimulation according to yet another example embodiment; and FIG.\",\n \"9 is a process flow diagram showing a method for electrostimulation according to an example embodiment.\",\n \"DETAILED DESCRIPTION OF EXAMPLE EMBODIMENTS The present teachings generally relate to systems and methods for electrical stimulation of any living object, including any tissue or fluid of a human, an animal, a plant, or any other natural object.\",\n \"The electrical stimulation is provided or caused by applying at least two electrodes to a live object or soil of a plant, where the electrodes are substantially of different metals or different metal alloys, and not connected to any electrical device such a voltage or current source.\",\n \"Most of tissues in a living object (e.g., a human, animal, or plant) include various liquids, such as water, a solution of water, or other liquids infused with salts, minerals, solvents, or other elements.\",\n \"It was found that the liquids or tissue of living objects can serve as an electrolyte or an electrically conducting solution.\",\n \"The two or more electrodes, when in contact with the living object or its fluids, create a difference in potentials between the electrodes without using any electrical current or voltage sources.\",\n \"The difference in potentials causes electrons to flow in the living object from one of the electrodes to another, while holes/ions can flow in the living object in the opposite direction.\",\n \"In this sense, one of the electrode can be considered as a cathode, while another electrode can be considered as an anode.\",\n \"The difference in potentials can be created only when the electrodes are of different metals or metal alloys.\",\n \"According to the present teachings, the electrodes can produce a difference of electric potential in a range from about 0.1 volts to about 1.4 volts, while the electrical current flowing from one electrode to another can be in a range from about 0.1 microampere to about 1,400 microampere.\",\n \"These ranges of voltages and electrical currents appear to be safe for humans and most of the animals and plants.\",\n \"The electrodes can be applied to or mounted on the living object or the soil of the pant at any distance therebetween (e.g., from one millimeter to two meters or even more) and still provide the difference in potentials.\",\n \"The inventors found that an electrical current will be caused by the electrodes when they are placed or attached to a living object at any distance therebetween.\",\n \"The electrostimulation therapy with the electrodes of this disclosure can be conveniently performed for long periods of time, ranging from about 1 hour to 24 hours or even more.\",\n \"The methods for electrostimulation of this disclosure can be used to treat many disorders of people, animals, and other living objects, including plants.\",\n \"For example, the present methods for electrostimulation can be used to treat infections, viral disorders, bacterial disorders, and reduce pain.\",\n \"It was unexpectedly found that the methods for electrostimulation can deactivate viruses and bacteria without harming normal tissues.\",\n \"Thus, the methods for electrostimulation may treat or assist in treating Acquired ImmunoDeficiency Syndrome (AIDS) or Human ImmunoDeficiency Virus (HIV) disorders.\",\n \"The electrostimulation can be also helpful or assisting in treating some or all cancers.\",\n \"In addition, the inventors found that the present teachings can be helpful in treating the following human disorders or conditions: urinary incontinence, enlarged prostate, arthritis, back pain, diabetic ulcers, fibromyalgia, headaches, herpes, neck pain, neuropathy, sciatica, shingles, sports injuries, tendon and ligament pain, rheumatism, carpal tunnel syndrome, inflammatory arthritis, fighting infectious diseases, viral infections, migraines, capsulitis, synovitis, disc diseases, stroke, tendonitis, bursitis, intractable pain, torticollis, soft tissue, bell's palsy, surgical incision, abdominal cramps, edema, whiplash, postop healing, injury, myofascial pain, chronic pain, temporomandibular joint dysfunction, sinus problems, acute pain, decubitus, myositis, facial lifting, skin rejuvenation, hypertension, macular degeneration, major depression, essential tremor, micro current deep brain stimulation, obsessive-compulsive disorder, Parkinson's disease, Alzheimer's disease, and so forth.\",\n \"The present teachings can be also helpful in improving well-being, and providing physiotherapy, anti-aging, and cosmetic treatments, among others.\",\n \"Notably, the present teachings do not require usage of any additional electrolytic solution or conductive gel to be placed between the electrodes and the living object.\",\n \"No reservoirs with a reducing agent and no reservoirs with an oxidizing agent are needed between the electrodes and the living object according to embodiments of this disclosure.\",\n \"Moreover, the present teachings of electrostimulation should not be used and should not be applied directly on wounds.\",\n \"The inventors of the present methods for electrostimulation suggest the following explanation of why these methods help in treating disorders and improving general well-being of living objects.\",\n \"Each tissue type in a body of a human and many animals has its own signature electrical frequency, which may be disrupted by an injury or a disease.\",\n \"The electrostimulation therapy according to the embodiments of this disclosure restores normal frequencies within human cells, resulting in remarkable improvements in treating pain, inflammation, and restoring a function of the cells.\",\n \"At the cellular level, the electrostimulation therapy stimulates a dramatic increase in adenosine triphosphate (ATP), the energy that fuels all biochemical functions in a human body.\",\n \"It also bumps up protein synthesis, which is necessary for tissue repair.\",\n \"The ensuing enhancement in blood flow and decrease in inflammation translates into reductions in pain and muscle spasms, as well as increased range of motion.\",\n \"The following detailed description of embodiments includes references to the accompanying drawings, which form a part of the detailed description.\",\n \"Approaches described in this section are not prior art to the claims and are not admitted to be prior art by inclusion in this section.\",\n \"The drawings show illustrations in accordance with example embodiments.\",\n \"These example embodiments, which are also referred to herein as “examples,” are described in enough detail to enable those skilled in the art to practice the present subject matter.\",\n \"The embodiments can be combined, other embodiments can be utilized, or structural, logical and operational changes can be made without departing from the scope of what is claimed.\",\n \"The following detailed description is, therefore, not to be taken in a limiting sense, and the scope is defined by the appended claims and their equivalents.\",\n \"For purposes of this patent document, the terms “or” and “and” shall mean “and/or” unless stated otherwise or clearly intended otherwise by the context of their use.\",\n \"The term “a” shall mean “one or more” unless stated otherwise or where the use of “one or more” is clearly inappropriate.\",\n \"The terms “comprise,” “comprising,” “include,” and “including” are interchangeable and not intended to be limiting.\",\n \"For example, the term “including” shall be interpreted to mean “including, but not limited to.” Additionally, all ranges provided herein include the upper and lower values of the range unless explicitly noted.\",\n \"For example, the term “about” shall mean a reasonable deviation of a value accompanying this term.\",\n \"If it is not specified otherwise, the term “about” may refer to a variation of 20% from an indicated value.\",\n \"In the case of a range of values, the term “about” may refer to a 20% variation from both the lower and upper limits of the range.\",\n \"Moreover, it shall be understood that when an element is referred to as being “on” or “connected” or “coupled” to another element, it can be directly on or connected or coupled to the other element or intervening elements can be present.\",\n \"In contrast, when an element is referred to as being “directly on” or “directly connected” or “directly coupled” to another element, there are no intervening elements present.\",\n \"Other words used to describe the relationship between elements should be interpreted in a like fashion (e.g., “between” versus “directly between,” “adjacent” versus “directly adjacent,” and so forth).\",\n \"Spatially relative terms, such as “beneath,” “below,” “lower,” “above,” “upper” and the like may be used to describe an element or feature's relationship to another element(s) and/or feature(s) as, for example, illustrated in the drawings.\",\n \"It shall be appreciated the spatially relative terms are intended to encompass different orientations of system for electrostimulation or its elements in use in addition to the orientation depicted in the figures.\",\n \"For example, if the system for electrostimulation or any of its components in the drawings is turned over, elements described as “below” and/or “beneath” other elements or features would then be oriented “above” the other elements or features.\",\n \"The system for electrostimulation or its components may be otherwise oriented (e.g., rotated 90 degrees or at other orientations) and the spatially relative descriptors used herein interpreted accordingly.\",\n \"The term “user” shall be construed to mean any individual, human, animal, or any other living object, using the system for electrostimulation according to any embodiment described herein.\",\n \"The term “user” shall also encompass a patient, client, customer, and the like.\",\n \"In some embodiments, the term “user” can be construed to mean a plant.\",\n \"The term “electrostimulation” shall be construed to mean a process for creating, producing, applying, or providing an electrical current in any tissue or liquid of any living object such as a human, animal, or plant.\",\n \"The terms “electrostimulation” and “electrical stimulation” can be used interchangeably.\",\n \"The term “electrode” shall be construed to mean any electric conductor of any shape or design.\",\n \"The electrode can be made of a metal or metal alloy.\",\n \"Each of the electrodes can be made as a single whole, although other implementations are also possible and within the scope of this disclosure.\",\n \"In certain embodiments of this disclosure, the electrodes have one or more homogeneous (solid, smooth) surfaces without any substantial irregularities.\",\n \"Now, exemplary embodiments are described with reference to the drawings.\",\n \"The drawings are schematic illustrations of idealized example embodiments.\",\n \"As such, variations from the shapes of the illustrations as a result, for example, of manufacturing techniques or tolerances, are to be expected.\",\n \"Thus, example embodiments discussed herein should not be construed as limited to the particular shapes of regions illustrated herein but are to include deviations in shapes that result, for example, from manufacturing.\",\n \"FIG.\",\n \"1 shows a front view of a user 100 wearing a system 110 for electrostimulation according to one example embodiment.\",\n \"The system 110 for electrostimulation includes two or more electrodes, where at least one of the electrodes is made of a metal or metal alloy that is different from other electrodes.\",\n \"In this example, the system 110 for electrostimulation includes two electrodes 110a and 110b, where the electrode 110a is made substantially of one metal, while the electrode 110b is made substantially of another metal.\",\n \"The metals for the electrodes of the system 110 can be selected from a wide range of different metals, including, for example, aluminum (Al), gold (Au), iron (Fe), copper (Cu), zinc (Zn), palladium (Pa), magnesium (Mg), platinum (Pl), silver (Ag), titanium (Ti), tungsten (W), and any alloys thereof.\",\n \"The electrodes 110aand 110b can also be made of various alloys containing chromium (Cr) that are used to make stainless steel.\",\n \"Thus, stainless steel (of any grade) can be used to make electrodes.\",\n \"In other words, the disclosed technology can utilize potential difference between various metals as well as various metal alloys.\",\n \"As discussed above, when the electrodes 110a and 110b are of different metals (or metal alloys), they produce a difference of electric potential in a range from about 0.1 volts to about 1.4 volts, while the electrical current flowing from one electrode to another can be in a range from about 1 microampere to about 1,400 microampere.\",\n \"The following table provides approximate differences of electric potential that are produced by different metal pairs: TABLE 1 Second Voltage (difference of Electrode potential), approximate values, First Electrode 110a 110b error can be up to 20% Al Au 0.7 volt Au Fe 0.04 volt Al Fe 0.6 volt Au Cu 0.01 volt Cu Fe 0.06 volt Au Zn 0.85 volt Zn Fe 0.9 volt Zn Cu 0.8 volt Zn Al 0.2 volt Al Pd 0.65 volt Au Pd Less than 0.01 volt Cu Pd 0.12 volt Fe Pd 0.04 volt Zn Pd 0.8 volt Al Ag 0.65 volt Au Ag 0.01 volt PD Ag 0.01 volt Cu Ag 0.15 volt Fe Ag 0.02 volt Zn Ag 0.85 volt Al Pl 0.6 volt Pl Pd Less than 0.01 volt Pl Au Less than 0.01 volt Pl Ag Less than 0.01 volt Cu Pl 0.08 volt Fe Pl 0.01 volt Zn Pl 0.7 volt Mg Zn 0.65 volt Mg Fe 1.3 volt Mg Cu 1.1 volt Mg Al 0.7 volt Mg Pl 1.2 volt Mg Au 1.4 volt Mg Pd 1.2 volt Mg Ag 1.2 volt Table 1 is applicable to all embodiments of this disclosure.\",\n \"Some example metal pairs for the electrodes 110a, 110b can be as follows.\",\n \"When the first electrode 110a is substantially of silver and the second electrode 110b is substantially of zinc, the difference of potential can be about 850 millivolts when the electrodes 110a, 110b are applied to a human body.\",\n \"When the first electrode 110a is substantially of iron and the second electrode 110b is substantially of zinc, the difference of potential can be about 900 millivolts when the electrodes 110a, 110b are applied to a human body.\",\n \"The electrical current between the electrodes 110a, 110b can vary and be in a range from about 1 microampere to about 1,400 microampere.\",\n \"It is important to mention that the electrodes 110a, 110b are not electrically or operatively connected to any medical device, including a voltage source or a current source.\",\n \"In some embodiments, however, the electrodes 110a, 110b can be electrically connected with one another to make a closed circuit (e.g., through any living tissue).\",\n \"Referring back to FIG.\",\n \"1, the electrodes 110a, 110b can be made in the form of a wearable item such as a bracelet, wristband, armband, leg band, necklace, or any piece of jewelry.\",\n \"The electrodes 110a, 110b can be placed, fixed, attached, secured, or provided at any location of the human body, animal, plant, or soil of the plant.\",\n \"For example, as shown in FIG.\",\n \"1, the first electrode 110a being in the form of a first bracelet, is provided on the right wrist of the user 100, and the second electrode 110b being in the form of a second bracelet, is provided on the left wrist of the user 100.The electrodes 110a, 110b can be provided in other forms too.\",\n \"For example, the electrodes can be attached to or provided by a skin patch, adhesive bandage, spray metal paint, topical, transdermal, intradermal, subcutaneous, intramuscular, intravenous, or other forms.\",\n \"The electrodes 110a, 110b can be also of different designs or shapes.\",\n \"For example, the electrodes 110a, 110b can be in the form of needles, discs, plates, panels, metal meshes, nanowires, metal dots, and the like.\",\n \"The distance between the electrodes 110a, 110b can be in a range from 10 millimeters to 2 meters or even more.\",\n \"The dimensions of the electrodes 110a, 110b can vary in any reasonable range.\",\n \"For example, the surface area of the electrodes 110a, 110b that are in contact with the user (or other living object) can be from about 1 square millimeter to about 200 square centimeter.\",\n \"FIG.\",\n \"2 shows a back view of a user 100 using a system 110 for electrostimulation according to another example embodiment.\",\n \"Here, system 110 for electrostimulation includes a plurality of electrodes 110a, 110b, 110c, 110d, 110e, 110f, 110g, and 110h.\",\n \"The number of electrodes is not limited to eight (like in this embodiment) and, generally, can be two or more electrodes.\",\n \"In this embodiment, the electrodes 110a, 110b, 110c, 110d, 110e, 110f, 110g, and 110h are in the form of acupuncture needles that are inserted into the user's skin.\",\n \"In one example, the electrode 110a is made of metal A, while other electrodes 110b-110h can be made of metal B.\",\n \"In another example, the electrodes 110a, 110b are made of metal A, while other electrodes 110c-110h can be made of metal B.\",\n \"In yet another example, the electrodes 110a, 110b, 110c are made of metal A, while other electrodes 110d-110h can be made of metal B.\",\n \"In yet another example, the electrodes 110a-110d are made of metal A, while other electrodes 110e-110h can be made of metal B.\",\n \"In yet another example, the electrodes 110a, 110c, 110e, 110g are made of metal A, while the electrodes 110b, 110d, 110f, 110h are made of metal B.\",\n \"In other example embodiments, the electrodes 110a-110h can be made of more than two different metals.\",\n \"For example, the electrode 110a is made of metal A, the electrode 110b is made of metal B, while other electrodes 110c-110h are made of metal C. In another example, the electrode 110a is made of metal A, the electrode 110b is made of metal B, the electrode 110c is made of metal C, while other electrodes 110d-110h are made of metal D. Any other combinations can be also used, but their description is not given in this document.\",\n \"FIG.\",\n \"3 shows a front view of a system 300 for electrostimulation according to yet another example embodiment.\",\n \"The system 300 for electrostimulation includes at least two separate wearable elements 300a and 300b.\",\n \"The wearable elements 300a and 300b can refer to a patch or a bandage.\",\n \"The wearable elements 300a, 300b include substrates 310a, 310b, respectively.\",\n \"The substrates 310a, 310b can be flexible substrates that are not electrically conductive.\",\n \"For example, each of the substrates 310a, 310b can include a pliable base, such as a medical grade 100% polyester fabric material; however, other materials can be also used such as gauze, mesh, fabric, polymer base, or other materials as long as they are pliable.\",\n \"Each of the substrates 310a, 310b includes a binder 320a, 320b, respectively, for releasable binding to a surface or skin of a living object (e.g., a human or animal).\",\n \"The binder 320a, 320b can be made of non-electrically conductive material such as a polymer or any other suitable medium used in certain coating, laminating, or adhesion techniques.\",\n \"Each of the substrates 310a, 310b also includes an electrode 110a, 110b, respectively.\",\n \"As discussed above, the electrodes 110a, 110b are of different metals or metal alloys.\",\n \"The electrodes 110a, 110b can be in the form of a metal plate, puck, disc, sphere, mesh, coating (e.g., a silver nanowire layer), film, layer, and the like.\",\n \"In certain embodiments, the wearable elements 300a and 300b are removably attached to a surface or skin of living object at a distance ranging from about 10 millimeters to about 2 meters or even more.\",\n \"The wearable elements 300a, 300b can remain attached to the surface or skin of living object for a period of at least one minute or more.\",\n \"In certain embodiments, there can be provided additional wearable elements similar to the wearable elements 300a, 300b.\",\n \"The number of such wearable elements is not limited.\",\n \"FIG.\",\n \"4 shows a side view of a wearable element 400 of a system for electrostimulation according to one example embodiment.\",\n \"The wearable element 400 can be an instant of wearable element 300a or 330b shown in FIG.\",\n \"3.The wearable element 400 includes a flexible substrate 310, a binder 320 in the form of polymeric adhesive layer, and an electrode 110.The electrode 110 is secured on a surface of the flexible substrate 310.The binder 320 is provided on the same surface of the flexible substrate 310 substantially around the electrode 110.When the wearable element 400 is in contact with a surface or skin 410 of a living object, the binder 320 provides adhesive connection of the entire wearable element 400 for a long period of time such that the electrode 110 directly contacts the surface or skin 410 of the living object.\",\n \"FIG.\",\n \"5 shows a side view of a wearable element 500 of a system for electrostimulation according to yet another example embodiment.\",\n \"The wearable element 500 can be an instant of wearable element 300a or 330b shown in FIG.\",\n \"3.The wearable element 500 includes a flexible substrate 310, a binder 320, for example, in the form of a polymeric adhesive layer, and an electrode 110.The binder 320 can exhibit electroconducting properties only when 320 is made of a non-conductive absorbing material and soaked in an electrolyte.\",\n \"In some example embodiments, the electrolyte can be substituted by tap water (rich with minerals).\",\n \"The bottom surface of electrode 110 is secured on the top surface of the flexible substrate 310.The bottom of the binder 320 is provided on the top surface of the electrode 110 and optionally on the top surface of the flexible substrate 310 where there is no electrode 110.When the wearable element 500 is in contact with the surface or skin 410 of the living object, the binder 320 provides adhesive connection of the entire wearable element 500 such that the electrode 110 indirectly contacts the surface or skin 410 of the living object.\",\n \"FIG.\",\n \"6 shows a front view of a system 600 for electrostimulation according to yet another example embodiment.\",\n \"Generally, the system 600 for electrostimulation can be a single wearable element such as a patch or a bandage.\",\n \"The system 600 includes a substrate 310, which can be of a non-electrically conductive, but flexible material.\",\n \"For example, the substrate 310 can include a pliable base, such as a medical grade 100% polyester fabric material; however, other materials can be also used such as gauze, mesh, fabric, polymer base, or other materials as long as they are pliable.\",\n \"The substrate 310 includes a binder 320 for releasable binding the entire system 600 to a surface or skin of a living object (e.g., a human, or animal).\",\n \"The binder 320 can be made of non-electrically conductive material such as a polymer or any other suitable medium used in certain coating, laminating, or adhesion techniques.\",\n \"The substrate 310 also includes two or more electrodes such as electrodes 110a, 110b.\",\n \"As discussed above, the electrodes 110a, 110b are of different metals or metal alloys.\",\n \"The electrodes 110a, 110b can be in the form of a metal plate, puck, disc, sphere, mesh, coating (e.g., a silver nanowire layer), film, layer, and the like.\",\n \"FIG.\",\n \"7 shows a front view of a system 700 for electrostimulation according to yet another example embodiment.\",\n \"The system 700 for electrostimulation can be directed to a single wearable element such as a patch or a bandage.\",\n \"The system 700 includes a substrate 310, which can be of a non-electrically conductive, but flexible material.\",\n \"For example, the substrate 310 can include a pliable base, such as a medical grade 100% polyester fabric material; however, other materials can be also used such as gauze, mesh, fabric, polymer base, or other materials as long as they are pliable.\",\n \"The substrate 310 includes a binder 320 for releasable binding the entire system 700 to a surface or skin of a living object (e.g., a human, or animal).\",\n \"The binder 320 can be made of non-electrically conductive material such as a polymer or any other suitable medium used in certain coating, laminating, or adhesion techniques.\",\n \"The substrate 310 also includes four or more electrodes such as electrodes 110a, 110b, 110c, and 110d.\",\n \"The electrodes 110a, 110b, 110c, and 110d can be in the form of a metal plate, puck, disc, sphere, mesh, coating (e.g., a silver nanowire layer), film, layer, and the like.\",\n \"As discussed above, the electrodes 110a, 110b, 110c, and 110d are of at least two different metals or metal alloys.\",\n \"For example, the electrode 110a is made of metal A, and the electrodes 110b, 110c, 110d are made of metal B.\",\n \"In another example, the electrode 110b is made of metal A, and the electrodes 110a, 110c, 110d are made of metal B.\",\n \"In yet another example, the electrode 110c is made of metal A, and the electrodes 110a, 110b, 110d are made of metal B.\",\n \"In yet another example, the electrode 110d is made of metal A, and the electrodes 110a, 110b, 110c are made of metal B.\",\n \"In yet another example, the electrodes 110a and 110b are made of metal A, and the electrodes 110c and 110d are made of metal B.\",\n \"In yet another example, the electrodes 110a and 110c are made of metal A, and the electrodes 110b and 110d are made of metal B.\",\n \"In yet another example, the electrode 110a is made of metal A, the electrode 110b is made of metal B, and the electrodes 110c and 110d are made of metal C. In yet another example, the electrode 110a is made of metal A, the electrode 110b is made of metal B, the electrode 110c is made of metal C, and the electrode 110d is made of metal D. Each of the metals A, B, C, and D can be selected from a group, comprising, for example, the following metals: aluminum (Al), gold (Au), iron (Fe), copper (Cu), zinc (Zn), palladium (Pa), magnesium (Mg), platinum (Pl), silver (Ag), and any alloy thereof.\",\n \"FIG.\",\n \"8 shows a front view of a system 800 for electrostimulation according to yet another example embodiment.\",\n \"The system 800 for electrostimulation can be directed to a single wearable element such as a patch or a bandage.\",\n \"The system 800 includes a substrate 310, which can be of a non-electrically conductive, but flexible material.\",\n \"For example, the substrate 310 can include a pliable base, such as a medical grade 100% polyester fabric material; however, other materials can be also used such as gauze, mesh, fabric, polymer base, or other materials as long as they are pliable.\",\n \"The substrate 310 includes a binder 320 for releasable binding the entire system 800 to a surface or skin of a living object (e.g., a human or animal).\",\n \"The binder 320 can be made of non-electrically conductive material such as a polymer or any other suitable medium used in certain coating, laminating, or adhesion techniques.\",\n \"The substrate 310 also includes four or more electrodes such as electrodes 110a, 110b, 110c, and 110d.\",\n \"The electrodes 110a, 110b, 110c, and 110d can be in the form of a metal plate, puck, disc, spheres, semi-spheres, mesh, coating (e.g., a silver nanowire layer), film, layer, and the like.\",\n \"As discussed above, the electrodes 110a, 110b, 110c, and 110d are made up of two different metals or different metal alloys.\",\n \"For example, the electrode 110a is made of metal A, and the electrode 110b is made of metal B, the electrode 110c is made of metal A, and the electrode 110d is made of metal B.\",\n \"Each of the metals of the electrodes 110a, 110b, 110c, and 110d can be selected from a group, comprising, for example, the following metals: aluminum (Al), gold (Au), iron (Fe), copper (Cu), zinc (Zn), palladium (Pa), magnesium (Mg), platinum (Pl), silver (Ag), and so forth.\",\n \"When electrodes 110a, 110b, 110c, and 110d are arranged in series, the output voltage for electrostimulation therapy can be increased up to a desired value, provided there can be any other suitable number of electrodes 110a, 110b, 110c, and 110d.\",\n \"Still referring to FIG.\",\n \"8, there can be provided electrolyte layers 810a, 810b, 810c between the electrodes 110a-110d, respectively, as shown in the figure.\",\n \"The electrolyte layers 810a-810c can be of any suitable non-conductive absorbing materials.\",\n \"The embodiment shown in FIG.\",\n \"8 illustrates how the difference of potentials created by the electrodes can be increased up to several voltages; however, in order for the system 800 to operate efficiently, the two end electrodes 110a and 110d must be placed, arranged, fixed, or attached onto the skin of the user: human or animal.\",\n \"The rest of the elements of system 800, in particular, the electrolyte layer 810a, the electrode 110b, the electrolyte layer 810b, the electrode 110c, and the electrolyte layer 810c should not meet the skin of the user.\",\n \"The electrodes 110a-110d are electrically interconnected in series using the electrolyte layers 810a-810c.\",\n \"In this case, the output voltage of the system 800 will be equal to a sum of the voltages generated by pairs of the electrodes 110a-110b, 110b-110c, and 110c-110d.\",\n \"FIG.\",\n \"9 is a process flow diagram showing a method 900 for electrostimulation according to an example embodiment.\",\n \"The method 900 may have additional steps not shown herein, but which can be evident for those skilled in the art from the present disclosure.\",\n \"The method 900 may also have fewer steps than outlined below.\",\n \"At step 905, a first electrode 110a is attached, fixed, inserted, or provided to a user (human or animal) or soil of a plant at a first location.\",\n \"For these ends, a first wearable element can be provided that includes the first electrode 110a.\",\n \"The first wearable element can be placed, arranged, fixed, attached, or otherwise provided to the user or plant such that the first electrode 110a is in contact with a tissue or liquid of the user or plant.\",\n \"In some embodiments, the first electrode 110a can be inserted into skin of the user (e.g., when the electrodes are in the form of a needle).\",\n \"In some embodiments, the first electrode 110a can be inserted into a blood vessel, vein, or arteria of the user in the form of a needle to provide electrostimulation therapy of blood or other fluids.\",\n \"At step 910, a second electrode 110b is attached, fixed, inserted, or provided to the user (human or animal) or the soil of the plant at a second location.\",\n \"For these ends, a second wearable element can be provided that includes the second electrode 110b.\",\n \"The second wearable element can be placed, arranged, fixed, attached, or otherwise provided to the user or soil of the plant such that the second electrode 110b is in contact with a tissue or liquid of the user or the soil of the plant.\",\n \"In some embodiments, the second electrode 110b can be inserted into skin of the user in the form of a needle.\",\n \"In some embodiments, the second electrode 110b can be inserted into a blood vessel, vein, or arteria of the user in the form of a needle to provide electrostimulation therapy of blood or other fluids.\",\n \"The first wearable element includes one of the following: a first bracelet, a first armband, a first leg band, and a necklace; however, the second wearable element can include one of the following: a second bracelet, a second armband, and a second leg band.\",\n \"The wearable elements can also refer to pieces of jewelry.\",\n \"It should be noted, however, that in other embodiments, wearable elements are not necessary.\",\n \"For example, each of the first electrode 110a and the second electrode 110b is included in an acupuncture needle.\",\n \"Thus, the operation of attachment of the first electrode to the user or the soil of the plant can include inserting the first electrode 110a through skin of the user or inserting in the soil of the plant; similarly, the operation of attachment of the second electrode 110b to the user or the soil of the plant includes inserting the second electrode 110b through skin of the user.\",\n \"As discussed above, the first electrode 110a is substantially of a first metal, while the second electrode 110b is substantially of a second metal, which differs from the first metal.\",\n \"Moreover, none of the electrodes is connected to any electrical device.\",\n \"In addition, the first location differs from the second location.\",\n \"After the first electrode and the second electrode are in contact with the user or the soil of the plant, they cause an electrical current to flow via at least a portion of the user or the soil of the plant.\",\n \"At optional step 915, one or more additional electrodes (similar to electrodes 110a, 110b) can be attached, fixed, inserted, or provided to the user (human or animal) or the soil of the plant at additional locations.\",\n \"Similar to above, one or more additional wearable elements can be provided such that any of the additional electrodes is in contact with the tissue or liquid of the user or the soil of the plant.\",\n \"In some embodiments, the additional electrodes can be inserted into skin of the user or inserted into a blood vessel, vein, or arteria of the user to provide electrostimulation therapy of blood or other fluids.\",\n \"At step 920, the first electrode 110a, the second electrode 110b, and all other additional electrodes (if any) are maintained at their locations of the user or the soil of the plant for a predetermined period.\",\n \"The predetermined period can be in a range from about 1 hour to about 24 hours or more, during which electrostimulation therapy is provided.\",\n \"The electrostimulation therapy involves generation of the electrical current by the electrodes 110a, 110b, etc.\",\n \"in a range from about 0.1 microampere to about 1,400 microampere.\",\n \"At step 925, the first electrode 110a, the second electrode 110b, and all other additional electrodes (if any) are removed from the user or the soil of the plant after the predetermined period is elapsed.\",\n \"As discussed above, the method 900 for electrostimulation can treat various disorders or conditions of people, animals, and improve growth of the plants.\",\n \"Thus, the systems and methods for electrostimulation have been described.\",\n \"Although embodiments have been described with reference to specific example embodiments, it will be evident that various modifications and changes can be made to these example embodiments without departing from the broader spirit and scope of the present application.\",\n \"Accordingly, the specification and drawings are to be regarded in an illustrative rather than a restrictive sense.\"\n ]\n]"},"source":{"kind":"string","value":"Patent_15871994"}}},{"rowIdx":4493977,"cells":{"text":{"kind":"list like","value":[["Artificial sebum film and method of producing same","A method for producing an artificial sebum film is provided with in raw material component and relative ratio, 78.4%-2% of triglyceride, 1%-15% of wax and ester, 20%-35% of squalane, 0.1%-7% of free fatty acid, 0.1%-6% of phospholipid, 0.1%-10% of cholesterol ester, 0.1%-10% of cholesterol, 0.1%-10% of antioxidant and 0.1%-5% of cellular activity regulator.","The invention modifies the proportion of raw material composition of the artificial sebum film to reduce the negative effect generated by oxidation, and increase the proportion of squalane, so that the skin under high pollution can restore to the normal equilibrium state.","Further, antioxidants and cellular active regulators are added to prolong the oxidation time of artificial sebum film and replenish the adenosine triphosphate in the cells."],["1.An artificial sebum film comprising, in raw material component and relative ratio, 78.4%-2% of triglyceride, 1%-15% of wax and ester, 20%-35% of squalane, 0.1%-7% of free fatty acid, 0.1%-6% of phospholipid, 0.1%-10% of cholesterol ester, 0.1%-10% of cholesterol, and 0.1%-10% of antioxidant and 0.1%-5% of cellular activity regulator; wherein the antioxidant comprises either one of the camellia seed oil, vitamin E complex, vitamin C complex, wheat germ oil and unsaturated fatty acid or a combination of more than two, wherein the vitamin E complex refers to vitamin E or its derivatives, and the vitamin C complex refers to vitamin C or its derivatives; the cellular activity regulator comprises either one of the adenosine triphosphate and algae extract or the combination of the two; the triglyceride refers to triglyceride or its derivatives; the squalane refers to squalane or its derivatives; the cholesterol ester refers to cholesteryl ester or its derivatives.","2.The artificial sebum film of claim 1, wherein the camellia seed oil in the antioxidant especially refers to Taiwan camellia seed oil.","3.A method for producing an artificial sebum film comprising, in raw material component and relative ratio, 78.4%-2% of triglyceride, 1%-15% of wax and ester, 20%-35% of squalane, 0.1%-7% of free fatty acid, 0.1%-6% of phospholipid, 0.1%-10% of cholesterol ester, 0.1%-10% of cholesterol, 0.1%-10% of antioxidant and 0.1%-5% of cellular activity regulator; the triglyceride, the squalane, and the antioxidant are each heated and mixed at 60-90° C. to be completely dissolved to prepare a first mixed raw material; the wax and ester, the free fatty acid, the phospholipid, the cholesterol ester, and the cholesterol are heated and mixed at 60-90° C. to complete dissolution for preparing a second mixed raw material; the first mixed raw material and the second mixed raw material are subjected to uniform mixing/stirring and cooling to 40-50° C.; at this time, cellular activity regulator is added, followed by uniform mixing/stirring and cooling down to room temperature to obtain the artificial sebum film; the antioxidant comprises either one of the camellia seed oil, vitamin E complex, vitamin C complex, wheat germ oil and unsaturated fatty acid or a combination of more than two, wherein the vitamin E complex refers to vitamin E or its derivatives, and the vitamin C complex refers to vitamin C or its derivatives; the cellular activity regulator comprises either one of the adenosine triphosphate and algae extract or the combination of the two; the triglyceride refers to triglyceride or its derivatives; the squalane refers to squalane or its derivatives; and the cholesterol ester refers to cholesteryl ester or its derivatives.","4.The method of claim 3, wherein the camellia seed oil in the antioxidant especially refers to Taiwan camellia seed oil."],[" BACKGROUND OF THE INVENTION "],[" SUMMARY OF THE INVENTION It is therefore one object of the invention to provide an artificial sebum film comprising, in raw material component and relative ratio, 78.4%-2% of triglyceride, 1%-15% of wax and ester, 20%-35% of squalane, 0.1%-7% of free fatty acid, 0.1%-6% of phospholipid, 0.1%-10% of cholesterol ester, 0.1%-10% of cholesterol, 0.1%-10% of antioxidant and 0.1%-5% of cellular activity regulator.","The above and other objects, features and advantages of the invention will become apparent from the following detailed description.","detailed-description description=\"Detailed Description\" end=\"lead\"?"],["BACKGROUND OF THE INVENTION 1.Field of the Invention The invention relates to artificial sebum film and more particularly to an artificial sebum film and a method of producing same having improved characteristics.","2.Description of Related Art The well known artificial sebum film generally has the following disadvantages: firstly, it comprises triglyceride which is easily oxidized, easy to cause change in color and odor on long-term storage, and easy to cause decomposition of free fatty acid, leading to decrease in PH; secondly, if placed in a low temperature environment, it is easy to freeze or cause release of a specific high melting point component, resulting in changes in the composition.","In addition, due to the increasingly serious pollution (including PM2.5 suspended particles, UV light, high temperature and other factors), the barrier capacity of the sebum layer of residents living in highly polluted areas (such as the densely populated cities) is generally insufficient.","Based on the above content, the current artificial sebum film may have shortcomings of easy oxidation and poor stability.","In addition, facing the increasing adverse environmental situation, after reaction with pollutants, the existing sebum composition will result in decrease in barrier degree to be unable to effectively protect skins.","Thus, the need for improvement still exists.","SUMMARY OF THE INVENTION It is therefore one object of the invention to provide an artificial sebum film comprising, in raw material component and relative ratio, 78.4%-2% of triglyceride, 1%-15% of wax and ester, 20%-35% of squalane, 0.1%-7% of free fatty acid, 0.1%-6% of phospholipid, 0.1%-10% of cholesterol ester, 0.1%-10% of cholesterol, 0.1%-10% of antioxidant and 0.1%-5% of cellular activity regulator.","The above and other objects, features and advantages of the invention will become apparent from the following detailed description.","DETAILED DESCRIPTION OF THE INVENTION An artificial sebum film of the invention comprises, in raw material component and relative ratio, 78.4%-2% of triglyceride, 1%-15% of wax and ester, 20%-35% of squalane, 0.1%-7% of free fatty acid, 0.1%-6% of phospholipid, 0.1%-10% of cholesterol ester, 0.1%-10% of cholesterol, 0.1%-10% of antioxidant and 0.1%-5% of cellular activity regulator.","A method for producing an artificial sebum film of the invention comprises, in raw material component and relative ratio, 78.4%-2% of triglyceride, 1%-15% of wax and ester, 20%-35% of squalane, 0.1%-7% of free fatty acid, 0.1%-6% of phospholipid, 0.1%-10% of cholesterol ester, 0.1%-10% of cholesterol, 0.1%-10% of antioxidant and 0.1%-5% of cellular activity regulator.","The triglyceride, the squalane, and the antioxidant are each heated and mixed at 70° C. to complete dissolution for preparing a first mixed raw material.","The wax and ester, the free fatty acid, the phospholipid, the cholesterol ester, and the cholesterol are heated and mixed at 70° C. to complete dissolution for preparing a second mixed raw material.","The first mixed raw material and the second mixed raw material are subjected to uniform mixing/stirring and cooling to 40-50° C. At this time, cellular activity regulator is added, followed by uniform mixing/stirring and cooling down to room temperature to obtain the artificial sebum film, wherein the heating temperature may also be set at 60-90° C. For the triglyceride, triglyceride can be used or triglyceride derivatives may be used as a substitute.","For the squalane, squalane can be used or squalane derivatives may be used as a substitute.","For the cholesterol ester, cholesterol ester can be used or cholesterol ester derivatives may be used as a substitute.","In addition, for the antioxidant, Taiwan camellia seed oil is used; for the wax and ester, lanolin is used; for the free fatty acid, palmitic acid is used; for the phospholipid, lecithin is used; for the cholesterol ester, lanosterol ester is used; for the cellular activity regulator, adenosine triphosphate is used.","The antioxidant may also be selected from either one of the camellia seed oil, vitamin E complex, vitamin C complex, wheat germ oil and unsaturated fatty acid or a combination of more than two, wherein the vitamin E complex refers to vitamin E or its derivatives, and the vitamin C complex refers to vitamin C or its derivatives.","The cellular activity regulator may also be selected from either one of the adenosine triphosphate and algae extract or the combination of the two.","The difference between the artificial sebum film of the invention and the commonly known techniques lies mainly in the lower content of the triglyceride in order to reduce the negative effects of oxidation likelihood and the free fatty acid release.","In addition, increasing the proportion of squalane in the composition may counteract the rapid loss of squalane in harsh environment, and may also help restore the skin in highly polluted environment to normal equilibrium state.","Furthermore, lecithin is added as the phospholipid to coat the periphery of the artificial sebum film to form liposome having a sphere of 0.025 μm to 3.5 μm, so that the artificial sebum film can be rapidly and deeply permeated and delivered into the skin to achieve the effect of filling the skin barrier.","The artificial sebum film of the invention is additionally added with camellia seed oil (using exclusive Taiwan camellia seed oil) as the highly effective antioxidant to reduce lipid oxidation and effectively prolong the preservation period of artificial sebum film.","In particular, in the field of anti-oxidation, it has been reported in the literature that camellia seed oil comprises rich antioxidant components such as catechins, chlorophyll, saponins, vitamin A, vitamin E, and unsaturated fatty acid and the like, and thus has the effect of scavenging free radicals.","Further, clinical medicine pointed out that the camellia seed oil can reduce the chance of vascular embolism, and has effects of anti-aging, regulating blood lipids and blood sugar, relaxing the bowels, and liver protection etc.","In the field of nutrition, it has the reputation of “plant gold” and comprises about 0.5% squalene, which can promote blood circulation, activate body function cells, reduce inflammation and sterilization, repair cells, and accelerate wound healing.","The artificial sebum film of the invention is further added with adenosine triphosphate as the cellular active substance, so as to induce the cells to generate adenosine triphosphate by themselves and promote the cell respiration, thereby enhancing the function of cell metabolism and helping restore the skins in the highly polluted environment to the normal equilibrium state.","The artificial sebum film of the invention not only has skin moisturizing effect, but also has the functions of high anti-oxidation, high permeability to assist the skin in the highly polluted environment to restore to the normal sebum composition.","Moreover, it combines with rapid and in-depth permeation technology of liposome to achieve the benefits of both replenishing intercellular lipid and constructing complete sebum film system.","While the invention has been described in terms of preferred embodiments, those skilled in the art will recognize that the invention can be practiced with modifications within the spirit and scope of the appended claims."]],"string":"[\n [\n \"Artificial sebum film and method of producing same\",\n \"A method for producing an artificial sebum film is provided with in raw material component and relative ratio, 78.4%-2% of triglyceride, 1%-15% of wax and ester, 20%-35% of squalane, 0.1%-7% of free fatty acid, 0.1%-6% of phospholipid, 0.1%-10% of cholesterol ester, 0.1%-10% of cholesterol, 0.1%-10% of antioxidant and 0.1%-5% of cellular activity regulator.\",\n \"The invention modifies the proportion of raw material composition of the artificial sebum film to reduce the negative effect generated by oxidation, and increase the proportion of squalane, so that the skin under high pollution can restore to the normal equilibrium state.\",\n \"Further, antioxidants and cellular active regulators are added to prolong the oxidation time of artificial sebum film and replenish the adenosine triphosphate in the cells.\"\n ],\n [\n \"1.An artificial sebum film comprising, in raw material component and relative ratio, 78.4%-2% of triglyceride, 1%-15% of wax and ester, 20%-35% of squalane, 0.1%-7% of free fatty acid, 0.1%-6% of phospholipid, 0.1%-10% of cholesterol ester, 0.1%-10% of cholesterol, and 0.1%-10% of antioxidant and 0.1%-5% of cellular activity regulator; wherein the antioxidant comprises either one of the camellia seed oil, vitamin E complex, vitamin C complex, wheat germ oil and unsaturated fatty acid or a combination of more than two, wherein the vitamin E complex refers to vitamin E or its derivatives, and the vitamin C complex refers to vitamin C or its derivatives; the cellular activity regulator comprises either one of the adenosine triphosphate and algae extract or the combination of the two; the triglyceride refers to triglyceride or its derivatives; the squalane refers to squalane or its derivatives; the cholesterol ester refers to cholesteryl ester or its derivatives.\",\n \"2.The artificial sebum film of claim 1, wherein the camellia seed oil in the antioxidant especially refers to Taiwan camellia seed oil.\",\n \"3.A method for producing an artificial sebum film comprising, in raw material component and relative ratio, 78.4%-2% of triglyceride, 1%-15% of wax and ester, 20%-35% of squalane, 0.1%-7% of free fatty acid, 0.1%-6% of phospholipid, 0.1%-10% of cholesterol ester, 0.1%-10% of cholesterol, 0.1%-10% of antioxidant and 0.1%-5% of cellular activity regulator; the triglyceride, the squalane, and the antioxidant are each heated and mixed at 60-90° C. to be completely dissolved to prepare a first mixed raw material; the wax and ester, the free fatty acid, the phospholipid, the cholesterol ester, and the cholesterol are heated and mixed at 60-90° C. to complete dissolution for preparing a second mixed raw material; the first mixed raw material and the second mixed raw material are subjected to uniform mixing/stirring and cooling to 40-50° C.; at this time, cellular activity regulator is added, followed by uniform mixing/stirring and cooling down to room temperature to obtain the artificial sebum film; the antioxidant comprises either one of the camellia seed oil, vitamin E complex, vitamin C complex, wheat germ oil and unsaturated fatty acid or a combination of more than two, wherein the vitamin E complex refers to vitamin E or its derivatives, and the vitamin C complex refers to vitamin C or its derivatives; the cellular activity regulator comprises either one of the adenosine triphosphate and algae extract or the combination of the two; the triglyceride refers to triglyceride or its derivatives; the squalane refers to squalane or its derivatives; and the cholesterol ester refers to cholesteryl ester or its derivatives.\",\n \"4.The method of claim 3, wherein the camellia seed oil in the antioxidant especially refers to Taiwan camellia seed oil.\"\n ],\n [\n \" BACKGROUND OF THE INVENTION \"\n ],\n [\n \" SUMMARY OF THE INVENTION It is therefore one object of the invention to provide an artificial sebum film comprising, in raw material component and relative ratio, 78.4%-2% of triglyceride, 1%-15% of wax and ester, 20%-35% of squalane, 0.1%-7% of free fatty acid, 0.1%-6% of phospholipid, 0.1%-10% of cholesterol ester, 0.1%-10% of cholesterol, 0.1%-10% of antioxidant and 0.1%-5% of cellular activity regulator.\",\n \"The above and other objects, features and advantages of the invention will become apparent from the following detailed description.\",\n \"detailed-description description=\\\"Detailed Description\\\" end=\\\"lead\\\"?\"\n ],\n [\n \"BACKGROUND OF THE INVENTION 1.Field of the Invention The invention relates to artificial sebum film and more particularly to an artificial sebum film and a method of producing same having improved characteristics.\",\n \"2.Description of Related Art The well known artificial sebum film generally has the following disadvantages: firstly, it comprises triglyceride which is easily oxidized, easy to cause change in color and odor on long-term storage, and easy to cause decomposition of free fatty acid, leading to decrease in PH; secondly, if placed in a low temperature environment, it is easy to freeze or cause release of a specific high melting point component, resulting in changes in the composition.\",\n \"In addition, due to the increasingly serious pollution (including PM2.5 suspended particles, UV light, high temperature and other factors), the barrier capacity of the sebum layer of residents living in highly polluted areas (such as the densely populated cities) is generally insufficient.\",\n \"Based on the above content, the current artificial sebum film may have shortcomings of easy oxidation and poor stability.\",\n \"In addition, facing the increasing adverse environmental situation, after reaction with pollutants, the existing sebum composition will result in decrease in barrier degree to be unable to effectively protect skins.\",\n \"Thus, the need for improvement still exists.\",\n \"SUMMARY OF THE INVENTION It is therefore one object of the invention to provide an artificial sebum film comprising, in raw material component and relative ratio, 78.4%-2% of triglyceride, 1%-15% of wax and ester, 20%-35% of squalane, 0.1%-7% of free fatty acid, 0.1%-6% of phospholipid, 0.1%-10% of cholesterol ester, 0.1%-10% of cholesterol, 0.1%-10% of antioxidant and 0.1%-5% of cellular activity regulator.\",\n \"The above and other objects, features and advantages of the invention will become apparent from the following detailed description.\",\n \"DETAILED DESCRIPTION OF THE INVENTION An artificial sebum film of the invention comprises, in raw material component and relative ratio, 78.4%-2% of triglyceride, 1%-15% of wax and ester, 20%-35% of squalane, 0.1%-7% of free fatty acid, 0.1%-6% of phospholipid, 0.1%-10% of cholesterol ester, 0.1%-10% of cholesterol, 0.1%-10% of antioxidant and 0.1%-5% of cellular activity regulator.\",\n \"A method for producing an artificial sebum film of the invention comprises, in raw material component and relative ratio, 78.4%-2% of triglyceride, 1%-15% of wax and ester, 20%-35% of squalane, 0.1%-7% of free fatty acid, 0.1%-6% of phospholipid, 0.1%-10% of cholesterol ester, 0.1%-10% of cholesterol, 0.1%-10% of antioxidant and 0.1%-5% of cellular activity regulator.\",\n \"The triglyceride, the squalane, and the antioxidant are each heated and mixed at 70° C. to complete dissolution for preparing a first mixed raw material.\",\n \"The wax and ester, the free fatty acid, the phospholipid, the cholesterol ester, and the cholesterol are heated and mixed at 70° C. to complete dissolution for preparing a second mixed raw material.\",\n \"The first mixed raw material and the second mixed raw material are subjected to uniform mixing/stirring and cooling to 40-50° C. At this time, cellular activity regulator is added, followed by uniform mixing/stirring and cooling down to room temperature to obtain the artificial sebum film, wherein the heating temperature may also be set at 60-90° C. For the triglyceride, triglyceride can be used or triglyceride derivatives may be used as a substitute.\",\n \"For the squalane, squalane can be used or squalane derivatives may be used as a substitute.\",\n \"For the cholesterol ester, cholesterol ester can be used or cholesterol ester derivatives may be used as a substitute.\",\n \"In addition, for the antioxidant, Taiwan camellia seed oil is used; for the wax and ester, lanolin is used; for the free fatty acid, palmitic acid is used; for the phospholipid, lecithin is used; for the cholesterol ester, lanosterol ester is used; for the cellular activity regulator, adenosine triphosphate is used.\",\n \"The antioxidant may also be selected from either one of the camellia seed oil, vitamin E complex, vitamin C complex, wheat germ oil and unsaturated fatty acid or a combination of more than two, wherein the vitamin E complex refers to vitamin E or its derivatives, and the vitamin C complex refers to vitamin C or its derivatives.\",\n \"The cellular activity regulator may also be selected from either one of the adenosine triphosphate and algae extract or the combination of the two.\",\n \"The difference between the artificial sebum film of the invention and the commonly known techniques lies mainly in the lower content of the triglyceride in order to reduce the negative effects of oxidation likelihood and the free fatty acid release.\",\n \"In addition, increasing the proportion of squalane in the composition may counteract the rapid loss of squalane in harsh environment, and may also help restore the skin in highly polluted environment to normal equilibrium state.\",\n \"Furthermore, lecithin is added as the phospholipid to coat the periphery of the artificial sebum film to form liposome having a sphere of 0.025 μm to 3.5 μm, so that the artificial sebum film can be rapidly and deeply permeated and delivered into the skin to achieve the effect of filling the skin barrier.\",\n \"The artificial sebum film of the invention is additionally added with camellia seed oil (using exclusive Taiwan camellia seed oil) as the highly effective antioxidant to reduce lipid oxidation and effectively prolong the preservation period of artificial sebum film.\",\n \"In particular, in the field of anti-oxidation, it has been reported in the literature that camellia seed oil comprises rich antioxidant components such as catechins, chlorophyll, saponins, vitamin A, vitamin E, and unsaturated fatty acid and the like, and thus has the effect of scavenging free radicals.\",\n \"Further, clinical medicine pointed out that the camellia seed oil can reduce the chance of vascular embolism, and has effects of anti-aging, regulating blood lipids and blood sugar, relaxing the bowels, and liver protection etc.\",\n \"In the field of nutrition, it has the reputation of “plant gold” and comprises about 0.5% squalene, which can promote blood circulation, activate body function cells, reduce inflammation and sterilization, repair cells, and accelerate wound healing.\",\n \"The artificial sebum film of the invention is further added with adenosine triphosphate as the cellular active substance, so as to induce the cells to generate adenosine triphosphate by themselves and promote the cell respiration, thereby enhancing the function of cell metabolism and helping restore the skins in the highly polluted environment to the normal equilibrium state.\",\n \"The artificial sebum film of the invention not only has skin moisturizing effect, but also has the functions of high anti-oxidation, high permeability to assist the skin in the highly polluted environment to restore to the normal sebum composition.\",\n \"Moreover, it combines with rapid and in-depth permeation technology of liposome to achieve the benefits of both replenishing intercellular lipid and constructing complete sebum film system.\",\n \"While the invention has been described in terms of preferred embodiments, those skilled in the art will recognize that the invention can be practiced with modifications within the spirit and scope of the appended claims.\"\n ]\n]"},"source":{"kind":"string","value":"Patent_15871997"}}},{"rowIdx":4493978,"cells":{"text":{"kind":"list like","value":[["DYNAMIC GENERATION OF DATABASE QUERIES IN QUERY BUILDERS","A query builder provided according to an aspect of the present invention facilitates users to conveniently generate database queries directed to database servers storing data elements organized according to attributes.","In an embodiment, configuration data indicating a comparison predicate to be used for each combination of an attribute and a conditional operation is maintained.","A user may then provide as inputs a first attribute, a first conditional operation and a first value.","In response, the query builder examines the configuration data to determine a first comparison predicate specified for the combination of the first attribute and the first conditional operation.","The query builder incorporates the first value in the first comparison predicate to construct a second comparison predicate and then forms a first database query with the second comparison predicate."],["1.A method of generating database queries directed to a database server implemented according to a relational database technology, said database server storing data elements organized as tables according to said relational database technology, with each table containing a corresponding set of columns, wherein each column is identified by a corresponding column name, said method comprising: receiving from an administrator a configuration data containing a plurality of entries, each entry specifying a corresponding comparison predicate to be used for a respective combination of a common name and a conditional operation, wherein the comparison predicate of each entry specifies a manner in which data corresponding to said common name can be retrieved from said database server according to said relational database technology based on said column names; storing said configuration data in a persistent storage; receiving from a user an input data specifying a first common name, a first conditional operation and a first value, wherein said plurality of entries are present stored in said persistent storage as said configuration data prior to said receiving; examining said configuration data to identify a first entry of said plurality of entries, said first entry having said respective combination which matches the combination of said first common name and said first conditional operation, wherein said first entry specifies a first comparison predicate for the combination, wherein said first comparison predicate specifies the column name of a first column in a first table and a second column in a second table according to said relational database technology, wherein the column name of said first column is represented as a text which is different from that representing said first common name; incorporating said first value in said first comparison predicate to construct a second comparison predicate, wherein said second comparison predicate includes the column names of said first column and said second column; forming a first database query with said second comparison predicate including the column names of said first column and said second column, wherein said first database query is formed according to said relational database technology, wherein said first database query, upon execution in said database server causes retrieval of data in said first column corresponding to said first common name in view of said first database query including the column name of said first column and constrains the data in said first column by the values in said second column in view of said first database query including the column name of said second column.","2.The method of claim 1, wherein said first database query is an SQL (structured query language) query specifying a join operation between said first table and said second table based on said second column.","3.The method of claim 2, wherein said forming comprises including said second comparison predicate in a WHERE clause of said SQL query.","4.The method of claim 3, wherein said forming further comprises including a set of columns to be retrieved in a SELECT clause of said SQL query, and a set of tables containing said set of columns in a FROM clause of said SQL query.","5.The method of claim 1, wherein said user does not specify said second column as a part of said input data.","6.A non-transitory machine readable medium storing one or more sequences of instructions for causing a system to generate database queries directed to a database server implemented according to a relational database technology, said database server storing data elements organized as tables according to said relational database technology, with each table containing a corresponding set of columns, wherein each column is identified by a corresponding column name, wherein execution of said one or more instructions by one or more processors contained in said system causes said system to perform the actions of: receiving from an administrator a configuration data containing a plurality of entries, each entry specifying a corresponding comparison predicate to be used for a respective combination of a common name and a conditional operation, wherein the comparison predicate of each entry specifies a manner in which data corresponding to said common name can be retrieved from said database server according to said relational database technology based on said column names; storing said configuration data in a persistent storage; receiving from a user an input data specifying a first common name, a first conditional operation and a first value, wherein said plurality of entries are present stored in said persistent storage as said configuration data prior to said receiving; examining said configuration data to identify a first entry of said plurality of entries, said first entry having said respective combination which matches the combination of said first common name and said first conditional operation, wherein said first entry specifies a first comparison predicate for the combination, wherein said first comparison predicate specifies the column name of a first column in a first table and a second column in a second table according to said relational database technology, wherein the column name of said first column is represented as a text which is different from that representing said first common name; incorporating said first value in said first comparison predicate to construct a second comparison predicate, wherein said second comparison predicate includes the column names of said first column and said second column; forming a first database query with said second comparison predicate including the column names of said first column and said second column, wherein said first database query is formed according to said relational database technology, wherein said first database query, upon execution in said database server causes retrieval of data in said first column corresponding to said first common name in view of said first database query including the column name of said first column and constrains the data in said first column by the values in said second column in view of said first database query including the column name of said second column.","7.The non-transitory machine readable medium of claim 6, wherein said first database query an SQL (structured query language) query specifying a join operation between said first table and said second table based on said second column.","8.The non-transitory machine readable medium of claim 7, wherein said forming comprises one or more instructions for including said second comparison predicate in a WHERE clause of said SQL query.","9.The non-transitory machine readable medium of claim 8, wherein said forming further comprises one or more instructions for including a set of columns to be retrieved in a SELECT clause of said SQL query, and a set of tables containing said set of columns in a FROM clause of said SQL query.","10.The non-transitory machine readable medium of claim 6, wherein said user does not specify said second column as a part of said input data.","11.A digital processing system comprising: a processor; a random access memory (RAM); a machine readable medium to store one or more instructions, which when retrieved into said RAM and executed by said processor causes said digital processing system to generate database queries directed to a database server implemented according to a relational database technology, said database server storing data elements organized as tables according to said relational database technology, with each table containing a corresponding set of columns, wherein each column is identified by a corresponding column name, said digital processing system performing the actions of: receiving from an administrator a configuration data containing a plurality of entries, each entry specifying a corresponding comparison predicate to be used for a respective combination of a common name and a conditional operation, wherein the comparison predicate of each entry specifies a manner in which data corresponding to said common name can be retrieved from said database server according to said relational database technology based on said column names; storing said configuration data in a persistent storage; receiving from a user an input data specifying a first common name, a first conditional operation and a first value, wherein said plurality of entries are present stored in said persistent storage as said configuration data prior to said receiving; examining said configuration data to identify a first entry of said plurality of entries, said first entry having said respective combination which matches the combination of said first common name and said first conditional operation, wherein said first entry specifies a first comparison predicate for the combination, wherein said first comparison predicate specifies the column name of a first column in a first table and a second column in a second table according to said relational database technology, wherein the column name of said first column is represented as a text which is different from that representing said first common name; incorporating said first value in said first comparison predicate to construct a second comparison predicate, wherein said second comparison predicate includes the column names of said first column and said second column; forming a first database query with said second comparison predicate including the column names of said first column and said second column, wherein said first database query is formed according to said relational database technology, wherein said first database query, upon execution in said database server causes retrieval of data in said first column corresponding to said first common name in view of said first database query including the column name of said first column and constrains the data in said first column by the values in said second column in view of said first database query including the column name of said second column.","12.The digital processing system of claim 11, wherein said first database query is an SQL (structured query language) query specifying a join operation between said first table and said second table based on said second column.","13.The digital processing system of claim 12, wherein said forming comprises including said second comparison predicate in a WHERE clause of said SQL query.","14.The digital processing system of claim 13, wherein said forming further comprises including a set of columns to be retrieved in a SELECT clause of said SQL query, and a set of tables containing said set of columns in a FROM clause of said SQL query.","15.The digital processing system of claim 11, wherein said user does not specify said second column as a part of said input data."],[" BACKGROUND OF THE INVENTION "],[" BRIEF DESCRIPTION OF THE DRAWINGS Example embodiments of the present invention will be described with reference to the accompanying drawings briefly described below.","FIG.","1 is a block diagram illustrating an example environment (computing system) in which several aspects of the present invention can be implemented.","FIG.","2 is a flowchart illustrating the manner in which a query builder generates database queries according to an aspect of the present invention.","FIG.","3 depicts a portion of a configuration data used by a query builder for generating SQL queries in one embodiment.","FIG.","4 depicts a graphical user interface (GUI) provided by a query builder in one embodiment.","FIG.","5 is a block diagram illustrating the details of a digital processing system in which several aspects of the present invention are operative by execution of appropriate executable modules.","detailed-description description=\"Detailed Description\" end=\"lead\"?","In the drawings, like reference numbers generally indicate identical, functionally similar, and/or structurally similar elements.","The drawing in which an element first appears is indicated by the leftmost digit(s) in the corresponding reference number."],["RELATED APPLICATIONS The present application is a continuation application of, and claims priority from, co-pending US Patent Application entitled, “DYNAMIC GENERATION OF DATABASE QUERIES IN QUERY BUILDERS”, application Ser.","No.","13/693,061, Filed: 4 Dec. 2012, and is incorporated in its entirety herewith.","BACKGROUND OF THE INVENTION Technical Field The present disclosure relates to server systems, and more specifically to dynamic generation of database queries in query builders.","Related Art Database queries refer to statements, which are used to access data in a database server.","Queries are typically received from external systems, and the result of processing each query is sent as a response to the corresponding requesting external system.","The queries may be received according to languages such as SQL (structured query language) well known in the relevant arts.","A query builder refers to a utility, which facilitates non-technical users (e.g., business managers) to form database queries.","In a typical implementation, a user merely provide various inputs required for forming desired conditions using a convenient GUI (graphical user interface), and the query builder then dynamically generates database queries containing the desired conditions based on the user provided inputs.","The generated queries may be later executed for accessing the data matching the specific conditions, from a database server.","Due to the use of such query builders, users may be shielded from various low level details such as syntax/semantics of language of the database queries (as specific to the database server), the underlying data organization (e.g., the specific tables and columns) in the database server, any required set-up for establishing connections with the database server, etc.","It may be desirable to simplify generation of such database queries even when some of the low level details are changed (for example, when the underlying data is reorganized).","BRIEF DESCRIPTION OF THE DRAWINGS Example embodiments of the present invention will be described with reference to the accompanying drawings briefly described below.","FIG.","1 is a block diagram illustrating an example environment (computing system) in which several aspects of the present invention can be implemented.","FIG.","2 is a flowchart illustrating the manner in which a query builder generates database queries according to an aspect of the present invention.","FIG.","3 depicts a portion of a configuration data used by a query builder for generating SQL queries in one embodiment.","FIG.","4 depicts a graphical user interface (GUI) provided by a query builder in one embodiment.","FIG.","5 is a block diagram illustrating the details of a digital processing system in which several aspects of the present invention are operative by execution of appropriate executable modules.","In the drawings, like reference numbers generally indicate identical, functionally similar, and/or structurally similar elements.","The drawing in which an element first appears is indicated by the leftmost digit(s) in the corresponding reference number.","DETAILED DESCRIPTION OF THE INVENTION 1.Overview A query builder provided according to an aspect of the present invention facilitates users to conveniently generate database queries directed to database servers storing data elements organized according to attributes.","In an embodiment, configuration data indicating a comparison predicate to be used for each combination of an attribute and a conditional operation is maintained.","A user may then provide as inputs a first attribute, a first conditional operation and a first value.","In response, the query builder examines the configuration data to determine a first comparison predicate specified for the combination of the first attribute and the first conditional operation.","The query builder incorporates the first value in the first comparison predicate to construct a second comparison predicate and then forms a first database query with the second comparison predicate.","In one embodiment, the database server is implemented according to a relational database technology, with the query builder forming the first database query according to SQL (structured query language) as an SQL query.","Several aspects of the present invention are described below with reference to examples for illustration.","However, one skilled in the relevant art will recognize that the invention can be practiced without one or more of the specific details or with other methods, components, materials and so forth.","In other instances, well-known structures, materials, or operations are not shown in detail to avoid obscuring the features of the invention.","Furthermore, the features/aspects described can be practiced in various combinations, though only some of the combinations are described herein for conciseness.","2.Example Environment FIG.","1 is a block diagram illustrating an example environment (computing system) in which several aspects of the present invention can be implemented.","The block diagram is shown containing network 110, database server 120, server system 130 (shown executing query builder 150) and end user systems 160A-160X.","Merely for illustration, only representative number/type of systems is shown in FIG.","1.Many environments often contain many more systems, both in number and type, depending on the purpose for which the environment is designed.","Each system/device of FIG.","1 is described below in further detail.","Network 110 provides connectivity between server system 130 and end user systems 160A-160X, and may be implemented using protocols such as Transmission Control Protocol (TCP) and/or Internet Protocol (IP), well known in the relevant arts.","In general, in TCP/IP environments, an IP packet is used as a basic unit of transport, with the source address being set to the IP address assigned to the source system from which the packet originates and the destination address set to the IP address of the target system to which the packet is to be eventually delivered.","A (IP) packet is said to be directed to a target system when the destination IP address of the packet is set to the (IP) address of the target system, such that the packet is eventually delivered to the target system by network 110.When the packet contains content such as port numbers, which specifies the target application, the packet may be said to be directed to such application as well.","Network 110 may be implemented using any combination of wire-based or wireless mediums.","Database server 120 represents a non-volatile (persistent) storage facilitating storage and retrieval of a collection of data by one or more applications executing in server system 130 (typically while processing various client requests).","In one embodiment, database server 120 is implemented using relational database technologies (that is, the data is organized in the form of tables and columns having corresponding names) and therefore provides storage and retrieval of data using structured queries such as SQL (Structured Query Language).","As is well known, SQL refers to a special-purpose, generally non-procedural language that supports the definition, manipulation, and control of data in systems implementing relational database technologies.","However, database server 120 can be implemented using other technologies (e.g., other languages, hierarchical databases) in alternative embodiments.","A SQL query is generally of the form “SELECT columns FROM tables WHERE comparison predicate”, where SELECT, FROM and WHERE are keyword in SQL, columns is a list of columns to be included in the result (with an asterisk (“*”) indicating all columns), tables is a list of tables from which data is to be retrieved, and comparison predicate is a logical condition used to restrict the rows returned by the query.","The comparison predicate typically contains one or more conditions (combined by logical operators such as AND, OR, NOT), with each condition specifying a column name (in a table), a comparison operator (such as “=”, “LIKE”, “IN”, etc.)","and a value to be compared with.","In addition, the SQL query may contain a GROUP BY clause for grouping rows based on specified columns, a HAVING clause specifying a predicate used to filter rows resulting from the GROUP BY clause, and a ORDER BY clause for specifying the order of rows in the result.","Each of end user systems 160A-160X represents a system such as a personal computer, workstation, mobile station, mobile phone, computing tablet, etc., used by users to generate (client) requests directed to applications executing in server system 130.The requests may be generated using appropriate user interfaces provided by applications executing in server system 130 or in the end user system.","In general, a user sends client requests for performing desired tasks and receives corresponding responses containing the results of performance of the requested tasks.","Each request is sent in the form of an IP packet directed to server system 130 (and corresponding application), with the IP packet including data identifying the desired tasks in the payload portion.","Server system 130 represents a system such as a web/application server executing applications capable of performing tasks requested by users.","In response to receiving a client requests from an end user system (such as 160A-160X), an application (to which the client request is directed to) executing in server system 130 performs the tasks specified in the request and sends the result of performance of the tasks to the requesting end user system.","The application may use data stored internally (for example, in a non-volatile storage/hard disk within the server system), external data (for example, in database server 120) and/or data received from external sources (e.g., from the user) in performing such tasks.","Query builder 150 facilitates non-technical users using end user systems 160A-160X to dynamically create SQL queries for retrieving data from database server 120.Query builder 150 provides a graphical user interface (GUI) on an end user system (such as 160A-160X) that enables a user to provide various inputs for forming desired conditions (using the GUI).","Query builder 150 then generates SQL queries based on the user provided inputs.","The generated SQL queries may then be executed (either by query builder 150 or by a different module/application, not shown) or stored for later execution.","In the following disclosure, query builder 150 is assumed to be a stand-alone block/application executing in server system 130.However, in alternative embodiments, query builder 150 may be implemented within an application executing in server system 130, as an external module such as a Dynamic-link library (DLL) that is used/shared by multiple applications executing in server system 130 or an application utility executing in one of the end user systems.","The features of the present invention can be implemented in such alternative embodiments as well, as will be apparent to one skilled in the relevant arts by reading the disclosure herein.","The manner in which query builder 150 dynamically generates SQL queries based on user provided inputs according to several aspects of the present invention is described below with examples.","3.Generating Database Queries FIG.","2 is a flowchart illustrating the manner in which a query builder generates database queries according to an aspect of the present invention.","The flowchart is described with respect to FIG.","1, and in relation to query builder 150 merely for illustration.","However, the features can be implemented in other environments (and in other servers) also without departing from the scope and spirit of various aspects of the present invention, as will be apparent to one skilled in the relevant arts by reading the disclosure provided herein.","In addition, some of the steps may be performed in a different sequence than that depicted below, as suited to the specific environment, as will be apparent to one skilled in the relevant arts.","Many of such implementations are contemplated to be covered by several aspects of the present invention.","The flow chart begins in step 201, in which control immediately passes to step 210.In step 210, query builder 150 maintains a configuration data indicating a comparison predicate to be used for each combination of a stored attribute and conditional operation of interest.","An (stored) attribute provides a common name for a group of data elements (that are stored in the database) sharing a characteristic.","In case of relational databases, a stored attribute eventually maps to a column of a table of a stored relational database.","Evaluation of a conditional operation against data items results in a logical result.","The conditional operation can be any of comparison operations (less than, equal to, between, etc.","), state operations (exists, missing, contained in, begins with, etc).","As noted above, a comparison predicate (specified as part of a SQL query) ensures that only the rows in the tables for which the comparison predicate evaluates to true are included in the result of processing of a corresponding SQL query.","The configuration data may be maintained in a persistent storage such as database server 120.The configuration data may be specified by developers of the query builder and/or applications executing in server system 130 or by administrators of server system 130.In step 230, query builder 150 receives, from a user, a stored attribute, a conditional operation of interest, and a value (hereafter together referred to as a “conditional expression”).","The conditional expression may be received from one of developer systems 160A-160X, in response to the user specifying the three inputs using a graphical user interface provided on the developer system by query builder 150.In step 250, query builder 150 determines the comparison predicate for the received combination of stored attribute and conditional operation.","The determination is performed by examining the configuration data, after retrieval from the persistent storage, and may be performed in a known way.","For example, query builder 150 may first identify a combination in the configuration data the received stored attribute and conditional operations, and then determine the comparison predicate associated with the identified combination.","In step 270, query builder 150 incorporates the received value in the determined comparison predicate.","According to a convention described below, the comparison predicate in the configuration data includes place holders for values to be specified by the users.","Incorporation in such convention therefore entails replacing the place holders with the corresponding user provided values.","Query builder 150 may perform any appropriate conversions of the received value before performing such replacements.","In step 290, query builder 150 forms a database query with the incorporated comparison predicate, for example, as the WHERE clause of a SQL query.","The columns and tables (in the FROM clause) may be determined by query builder 150 by inspecting the comparison predicate.","Alternatively, the configuration data may be designed to also indicate (in addition to the comparison predicate) the specific columns/tables to be included in the SQL query.","As noted above, the formed SQL query may be executed or stored for later execution.","The flow chart ends in step 299.Thus, query builder 150 dynamically generates SQL queries based on user provided inputs.","It should be noted that the steps of 230, 250 and 270 can be iterated by a user to specify a complex condition having multiple conditional expressions.","The step of 290 may be performed only after the user has specified the desired set of conditional expressions.","It may be appreciated that any changes required to SQL queries in view of situations such as changes to the business logic (such as the manner of retrieval) and/or the organization of data (such as the structures of the tables/columns), can be effected by modifying the comparison predicates in the configuration data (in view of the techniques described above).","The programming logic for the generation of the SQL query embedded within (the instructions constituting) query builder 150 need not accordingly be modified in response to such changes.","The manner in which query builder 150 dynamically generates SQL queries according to the foregoing description, is illustrated below with examples.","4.Illustrative Example FIGS.","3 and 4 together illustrate the manner in SQL queries are dynamically generated in query builders (in particular, query builder 150) in one embodiment.","Each of the Figures is described in detail below.","FIG.","3 depicts a portion of a configuration data used by a query builder (150) for generating SQL queries in one embodiment.","For illustration, the configuration data is shown maintained in the form of a table (300) in database server 120.However, in alternative embodiments, the configuration data may be maintained using other data formats such as extensible markup language (XML), as will be apparent to one skilled in the relevant arts by reading the disclosure herein.","Table 300 depicts portions of configuration data maintained by query builder 150.In particular, columns 321 “Attribute” and 322 “Condition” specifies a combination of the (name of) a stored attribute and a conditional operation, while columns 323 “Table” and 324 “Predicate” respectively specifies the table and comparison predicate for the corresponding combination.","Thus, each of rows 341-346 specifies the corresponding table and comparison predicate to be used for a combination of stored attribute and conditional operation.","For example, row 341 indicates that the table “V_RPT_PRODUCT’ table is to be included in the FROM clause and the predicate “V_RPT_CASE.CASE_ID=V_RPT_PRODUCT.CASE_ID and V_RPT_PRODUCT.PRODUCT_ID=(select PRODUCT ID from V_DRUG_NAME where upper(PRODUCT_NAME)=upper(‘#PARAM#’))” is to be used in the WHERE clause for the combination of the stored attribute “Company Product” and conditional operation “Equal to”.","It may be observed that the predicate contains the text “#PARAM#” indicating a place holder for a (user provided) value to be later incorporated.","Similarly other rows 342-346 specify the table and predicate to be used for corresponding combinations.","In the following description it is assumed that all the generated SQL queries retrieve the values in the default table/column “V_RPT_CASE.case_id” and that the default table “V_RPT_CASE” is to be included in the FROM clause in addition to the tables specified in column 423.However, in alternative embodiments, the specific columns to be retrieved and the specific tables to be used may be specified as part of configuration data (table 300), as will be apparent to one skilled in the relevant arts.","It may be appreciated that the configuration data indicates that different predicates are to be used for different combinations of stored attributes and conditional operations.","The predicates may be specified by a developer/administrator based on the underlying business logic (for example, how are company products to be retrieved in relation to cases) to be used, the data organization (tables V_RPT_CASE, V_RPT_REPORT) in database server 120, any optimizations that can be performed during retrieval, etc.","In a scenario that there is a change in the business logic or data organization, the developer/administrator is required to only modify the predicates in column 324 of table 300, with query builder 150 then using the modified predicates for the generation of the SQL queries.","Thus, query builder 150 maintains configuration data (300) indicating the specific comparison predicates to be used for each combination of stored attribute and conditional operation.","Query builder 150 then generates SQL queries based on such configuration data (300) and user provided inputs.","The manner in which a user is enabled to provide inputs for generating SQL queries is described below with examples.","5.Graphical User Interface FIG.","4 depicts a graphical user interface (GUI) provided by a query builder (150) in one embodiment.","Display area 400 depicts a portion of a user interface provided on a display unit (not shown in FIG.","1) associated with one of end user systems (assumed to be 160A, for illustration).","In one embodiment, display area 400 corresponds to a browser (as indicated by the text in display area 405) displaying a web page provided by query builder 150, in response to a user sending a request from end user system 160A.","Display area 420 enables a user to create a new query (advanced condition) by clicking the “Create Query” button and to view the results of executing previously created queries by clicking the “Query Results” button.","The description is continued assuming that the user has selected the “Create Query” button to specify a new query.","Display area 440 enables to user to name and save the newly created query, thereby enabling the user to later execute the saved query.","The text “” in display area 440 indicates that the user has not yet named/saved the current query.","Display area 450 enables the user to provide various inputs for forming desired conditional expressions.","In particular, the user specifies a stored attribute (by selecting or entering the name in the “Attribute” column), a conditional operation (by selecting from the options provided in “Condition” column), and a value to be used for comparison (by searching for or entering in the “Value” column).","The user may also combine multiple conditional expressions using logical operators such as AND, OR, AND NOT, etc.","(by selecting the appropriate option in the “Operator” column).","It may be observed that each of the conditional expressions is specified in a corresponding row (such as row 475) in display area 470.A user may select the buttons shown in display area 460 for adding new rows/conditions or removing older rows/conditions from display area 470.For example, a user may click/select the buttons labeled with a “+” in display area 460 to add a row (either before or after the currently selected row indicated by the dotted boundary, i.e., row 475) in display area 470, and may click/select the button labeled with a “x” in display area 460 to remove the currently selected row (i.e., row 475).","It may be appreciated that the conditional expressions specified in the set of rows in display area 470 represents a complex conditional expression based on which the SQL query is sought to be generated.","A user may also select the opening bracket “(” and closing bracket “)” columns to specify sub-expressions in the complex conditional expression in display area 370.An example of such a complex conditional expression having sub-expressions is “Report Type equal to Spontaneous AND (Country equal to United States OR Country equal to Australia)”, where Report Type and Country are specified in the “Attribute’ column; “equal to” is specified in the “Condition’ column; Spontaneous, United States and Australia are specified in the ‘Value’ column; “AND” and “OR” are specified in the ‘Operator’ column; and the opening and closing brackets are selected in the appropriate “(” and “)” columns.","Thus, a user using the user interface of FIG.","3 is facilitated to specify various inputs for forming the desired conditions/conditional expression.","The description is continued assuming that the user has specified the one conditional expression in the form “Company Product”, “Equal to” and “Vovern [Capsule, 500 mg]” shown in display area 470.The user may then (after specifying a name using an interface not shown) click/select the “Save” button in display area 480 to indicate that a SQL query is to be generated (based on the specified conditional expression) and stored for later execution.","Alternatively, the user may click on “Execute” button in display area 480 to indicate that a SQL query is to be generated and immediately executed.","In response to a user selecting the Save or Execute buttons, query builder 150 generates a SQL query based on the conditions/inputs specified by the user in display area 470.In the embodiment noted above, the browser sends the inputs specified in display area 470 in the form of IP packets directed to server system 130 (in particular query builder 150).","Query builder 150 then generates the SQL query in response to receiving the IP packets from the browser.","The manner in which query builder 150 generates/forms a SQL query based on the user provided inputs (of display area 470) and configuration data (300) is described below with examples.","6.Generating a SQL Query In response to receiving the user inputs “Company Product”, “Equal to” and “Vovern [Capsule, 500 mg]”, query builder 150 first examines configuration data 300 to determine the comparison predicate for the received combination of stored attribute “Company Product” and conditional operation “Equal to”.","Query builder 150 may accordingly identify that row 341 corresponds to the received combination and that predicate indicated in column 324 of row 341 is to be used in the SQL query.","Query builder 150 then incorporates the received value in the determined predicate by replacing the one occurrence of the text “#PARAM#” in the determined predicate with the received value “Vovern [Capsule, 500 mg]”.","Query builder 150 then forms the SQL query by using the default column “V_RPT_CASE.case id”, the tables “V RPT CASE” (default table) and “V_RPT_PRODUCT” (the value in column 323 of row 341) in the FROM clause and the incorporated predicate in the WHERE clause.","Thus, query builder 150 may form the below noted query in response to receiving the values shown in display area 470: SELECT_DISTINCT_V_RPT_CASE.","case id FROM V_RPT_CASE, V_RPT_PRODUCT WHERE (V_RPT_CASE.CASE_ID=V_RPT_PRODUCT.","CASE_ID and V_RPT_PRODUCT.PRODUCT_ID=(select PRODUCT_ID from V_DRUG_NAME where upper(PRODUCT_NAME)=upper(‘Vovern [Capsule, 500 mg]’)) Thus, query builder 150 generates a SQL query based on user provided inputs (shown in display area 470) and configuration data (300).","Query builder 150 may then execute or store (based on whether the user selected “Execute” button or “Save” button in display area 480) the above generated SQL query.","In a scenario that a complex condition (having multiple conditional expressions) is specified by the user in display area 470, query builder 150 may first identify the predicates for each of the combinations in the multiple conditional expressions, incorporate the values specified in the corresponding conditional expressions in the determined predicates and then combine the incorporated predicates based on the logical operators (AND, OR, etc.)","specified by the user.","The SQL query may then be formed using the combined predicate corresponding to all the conditional expressions in the complex condition.","Furthermore, query builder 150 may also receives data indicating sub-expressions and process them by adding corresponding sub-expressions in the generated SQL query.","It should be appreciated that though several features of the present invention are described above with respect to the “SELECT” SQL statement, in alternative embodiments, the features of the present invention may be implemented in the context of other types of conditional SQL statements (such as INSERT, UPDATE and DELETE) as well, as will be apparent to one skilled in the relevant arts by reading the disclosure herein.","It should be further appreciated that the features described above can be implemented in various embodiments as a desired combination of one or more of hardware, executable modules, and firmware.","The description is continued with respect to an embodiment in which various features are operative when corresponding executable modules are executed.","7.Digital Processing System FIG.","5 is a block diagram illustrating the details of digital processing system 500 in which several aspects of the present invention are operative by execution of appropriate executable modules.","Digital processing system 500 may correspond to any system (such as server system 130) executing query builder 150 or any one of end user systems 160A-160X.","Digital processing system 500 may contain one or more processors (such as a central processing unit (CPU) 510), random access memory (RAM) 520, secondary memory 530, graphics controller 560, display unit 570, network interface 580, and input/ output interface 590.All the components except display unit 570 may communicate with each other over communication path 550, which may contain several buses as is well known in the relevant arts.","CPU 510 may execute instructions stored in RAM 520 to provide several features of the present invention.","CPU 510 may contain multiple processing units, with each processing unit potentially being designed for a specific task.","Alternatively, CPU 510 may contain only a single general-purpose processing unit.","RAM 520 may receive instructions from secondary memory 530 using communication path 550.RAM 520 is shown currently containing software instructions constituting shared environment 525 and/or user programs 526.Shared environment 525 contains utilities shared by user programs, and such shared utilities include operating systems, virtual machines, etc., which provide a (common) run-time environment for execution of user programs 526 (such as browsers, email client software).","Graphics controller 560 generates display signals (e.g., in RGB format) to display unit 570 based on data/instructions received from CPU 510.Display unit 570 contains a display screen to display the images defined by the display signals (for example, portions of the user interface shown in FIG.","4).","Input/output interface 590 includes input as well as output devices to enable a user to interact with system 500 (for example, to interact with the user interface of FIG.","4 such as selecting the desired stored attributes, conditional operations, specifying values).","Network interface 580 provides the physical, electrical and protocol implementations that enable system 500 to communicate with other systems of FIG.","1 using protocols such as TCP/IP.","Secondary memory 530 (representing a non-transitory storage/medium) may contain hard drive 535, flash memory 536, and removable storage drive 537.Secondary memory 530 may store data (for example, portions of configuration data shown in FIG.","3, portions of the user provided inputs, portions of the generated SQL queries) and software instructions (for example, for performing the steps of FIG.","2), which enable digital processing system 500 to provide several features in accordance with the present invention, as described above.","Some or all of the data and instructions may be provided on removable storage unit 540, and the data and instructions may be read and provided by removable storage drive 537 to CPU 510.Floppy drive, magnetic tape drive, CD-ROM drive, DVD Drive, Flash memory, removable memory chip (PCMCIA Card, EPROM) are examples of such removable storage drive 537.Removable storage unit 540 may be implemented using medium and storage format compatible with removable storage drive 537 such that removable storage drive 537 can read the data and instructions.","Thus, removable storage unit 540 includes a computer readable storage medium having stored therein computer software and/or data.","However, the computer (or machine, in general) readable storage medium can be in other forms (e.g., non-removable, random access, etc.).","In this document, the term “computer program product” is used to generally refer to secondary memory 530.These computer program products are means for providing software to digital processing system 500.CPU 510 may retrieve the software instructions, and execute the instructions to provide various features of the present invention described above.","It should be understood that numerous specific details, relationships, and methods are set forth to provide a full understanding of the invention.","For example, many of the functions units described in this specification have been labeled as modules/blocks in order to more particularly emphasize their implementation independence.","Reference throughout this specification to “one embodiment”, “an embodiment”, or similar language means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention.","Thus, appearances of the phrases “in one embodiment”, “in an embodiment” and similar language throughout this specification may, but do not necessarily, all refer to the same embodiment.","Furthermore, the described features, structures, or characteristics of the invention may be combined in any suitable manner in one or more embodiments.","In the above description, numerous specific details are provided such as examples of programming, software modules, user selections, network transactions, database queries, database structures, hardware modules, hardware circuits, hardware chips, etc., to provide a thorough understanding of embodiments of the invention.","8.Conclusion While various embodiments of the present invention have been described above, it should be understood that they have been presented by way of example only, and not limitation.","Thus, the breadth and scope of the present invention should not be limited by any of the above-described exemplary embodiments, but should be defined only in accordance with the following claims and their equivalents.","It should be understood that the figures and/or screen shots illustrated in the attachments highlighting the functionality and advantages of the present invention are presented for example purposes only.","The present invention is sufficiently flexible and configurable, such that it may be utilized in ways other than that shown in the accompanying figures.","Further, the purpose of the following Abstract is to enable the Patent Office and the public generally, and especially the scientists, engineers and practitioners in the art who are not familiar with patent or legal terms or phraseology, to determine quickly from a cursory inspection the nature and essence of the technical disclosure of the application.","The Abstract is not intended to be limiting as to the scope of the present invention in any way."]],"string":"[\n [\n \"DYNAMIC GENERATION OF DATABASE QUERIES IN QUERY BUILDERS\",\n \"A query builder provided according to an aspect of the present invention facilitates users to conveniently generate database queries directed to database servers storing data elements organized according to attributes.\",\n \"In an embodiment, configuration data indicating a comparison predicate to be used for each combination of an attribute and a conditional operation is maintained.\",\n \"A user may then provide as inputs a first attribute, a first conditional operation and a first value.\",\n \"In response, the query builder examines the configuration data to determine a first comparison predicate specified for the combination of the first attribute and the first conditional operation.\",\n \"The query builder incorporates the first value in the first comparison predicate to construct a second comparison predicate and then forms a first database query with the second comparison predicate.\"\n ],\n [\n \"1.A method of generating database queries directed to a database server implemented according to a relational database technology, said database server storing data elements organized as tables according to said relational database technology, with each table containing a corresponding set of columns, wherein each column is identified by a corresponding column name, said method comprising: receiving from an administrator a configuration data containing a plurality of entries, each entry specifying a corresponding comparison predicate to be used for a respective combination of a common name and a conditional operation, wherein the comparison predicate of each entry specifies a manner in which data corresponding to said common name can be retrieved from said database server according to said relational database technology based on said column names; storing said configuration data in a persistent storage; receiving from a user an input data specifying a first common name, a first conditional operation and a first value, wherein said plurality of entries are present stored in said persistent storage as said configuration data prior to said receiving; examining said configuration data to identify a first entry of said plurality of entries, said first entry having said respective combination which matches the combination of said first common name and said first conditional operation, wherein said first entry specifies a first comparison predicate for the combination, wherein said first comparison predicate specifies the column name of a first column in a first table and a second column in a second table according to said relational database technology, wherein the column name of said first column is represented as a text which is different from that representing said first common name; incorporating said first value in said first comparison predicate to construct a second comparison predicate, wherein said second comparison predicate includes the column names of said first column and said second column; forming a first database query with said second comparison predicate including the column names of said first column and said second column, wherein said first database query is formed according to said relational database technology, wherein said first database query, upon execution in said database server causes retrieval of data in said first column corresponding to said first common name in view of said first database query including the column name of said first column and constrains the data in said first column by the values in said second column in view of said first database query including the column name of said second column.\",\n \"2.The method of claim 1, wherein said first database query is an SQL (structured query language) query specifying a join operation between said first table and said second table based on said second column.\",\n \"3.The method of claim 2, wherein said forming comprises including said second comparison predicate in a WHERE clause of said SQL query.\",\n \"4.The method of claim 3, wherein said forming further comprises including a set of columns to be retrieved in a SELECT clause of said SQL query, and a set of tables containing said set of columns in a FROM clause of said SQL query.\",\n \"5.The method of claim 1, wherein said user does not specify said second column as a part of said input data.\",\n \"6.A non-transitory machine readable medium storing one or more sequences of instructions for causing a system to generate database queries directed to a database server implemented according to a relational database technology, said database server storing data elements organized as tables according to said relational database technology, with each table containing a corresponding set of columns, wherein each column is identified by a corresponding column name, wherein execution of said one or more instructions by one or more processors contained in said system causes said system to perform the actions of: receiving from an administrator a configuration data containing a plurality of entries, each entry specifying a corresponding comparison predicate to be used for a respective combination of a common name and a conditional operation, wherein the comparison predicate of each entry specifies a manner in which data corresponding to said common name can be retrieved from said database server according to said relational database technology based on said column names; storing said configuration data in a persistent storage; receiving from a user an input data specifying a first common name, a first conditional operation and a first value, wherein said plurality of entries are present stored in said persistent storage as said configuration data prior to said receiving; examining said configuration data to identify a first entry of said plurality of entries, said first entry having said respective combination which matches the combination of said first common name and said first conditional operation, wherein said first entry specifies a first comparison predicate for the combination, wherein said first comparison predicate specifies the column name of a first column in a first table and a second column in a second table according to said relational database technology, wherein the column name of said first column is represented as a text which is different from that representing said first common name; incorporating said first value in said first comparison predicate to construct a second comparison predicate, wherein said second comparison predicate includes the column names of said first column and said second column; forming a first database query with said second comparison predicate including the column names of said first column and said second column, wherein said first database query is formed according to said relational database technology, wherein said first database query, upon execution in said database server causes retrieval of data in said first column corresponding to said first common name in view of said first database query including the column name of said first column and constrains the data in said first column by the values in said second column in view of said first database query including the column name of said second column.\",\n \"7.The non-transitory machine readable medium of claim 6, wherein said first database query an SQL (structured query language) query specifying a join operation between said first table and said second table based on said second column.\",\n \"8.The non-transitory machine readable medium of claim 7, wherein said forming comprises one or more instructions for including said second comparison predicate in a WHERE clause of said SQL query.\",\n \"9.The non-transitory machine readable medium of claim 8, wherein said forming further comprises one or more instructions for including a set of columns to be retrieved in a SELECT clause of said SQL query, and a set of tables containing said set of columns in a FROM clause of said SQL query.\",\n \"10.The non-transitory machine readable medium of claim 6, wherein said user does not specify said second column as a part of said input data.\",\n \"11.A digital processing system comprising: a processor; a random access memory (RAM); a machine readable medium to store one or more instructions, which when retrieved into said RAM and executed by said processor causes said digital processing system to generate database queries directed to a database server implemented according to a relational database technology, said database server storing data elements organized as tables according to said relational database technology, with each table containing a corresponding set of columns, wherein each column is identified by a corresponding column name, said digital processing system performing the actions of: receiving from an administrator a configuration data containing a plurality of entries, each entry specifying a corresponding comparison predicate to be used for a respective combination of a common name and a conditional operation, wherein the comparison predicate of each entry specifies a manner in which data corresponding to said common name can be retrieved from said database server according to said relational database technology based on said column names; storing said configuration data in a persistent storage; receiving from a user an input data specifying a first common name, a first conditional operation and a first value, wherein said plurality of entries are present stored in said persistent storage as said configuration data prior to said receiving; examining said configuration data to identify a first entry of said plurality of entries, said first entry having said respective combination which matches the combination of said first common name and said first conditional operation, wherein said first entry specifies a first comparison predicate for the combination, wherein said first comparison predicate specifies the column name of a first column in a first table and a second column in a second table according to said relational database technology, wherein the column name of said first column is represented as a text which is different from that representing said first common name; incorporating said first value in said first comparison predicate to construct a second comparison predicate, wherein said second comparison predicate includes the column names of said first column and said second column; forming a first database query with said second comparison predicate including the column names of said first column and said second column, wherein said first database query is formed according to said relational database technology, wherein said first database query, upon execution in said database server causes retrieval of data in said first column corresponding to said first common name in view of said first database query including the column name of said first column and constrains the data in said first column by the values in said second column in view of said first database query including the column name of said second column.\",\n \"12.The digital processing system of claim 11, wherein said first database query is an SQL (structured query language) query specifying a join operation between said first table and said second table based on said second column.\",\n \"13.The digital processing system of claim 12, wherein said forming comprises including said second comparison predicate in a WHERE clause of said SQL query.\",\n \"14.The digital processing system of claim 13, wherein said forming further comprises including a set of columns to be retrieved in a SELECT clause of said SQL query, and a set of tables containing said set of columns in a FROM clause of said SQL query.\",\n \"15.The digital processing system of claim 11, wherein said user does not specify said second column as a part of said input data.\"\n ],\n [\n \" BACKGROUND OF THE INVENTION \"\n ],\n [\n \" BRIEF DESCRIPTION OF THE DRAWINGS Example embodiments of the present invention will be described with reference to the accompanying drawings briefly described below.\",\n \"FIG.\",\n \"1 is a block diagram illustrating an example environment (computing system) in which several aspects of the present invention can be implemented.\",\n \"FIG.\",\n \"2 is a flowchart illustrating the manner in which a query builder generates database queries according to an aspect of the present invention.\",\n \"FIG.\",\n \"3 depicts a portion of a configuration data used by a query builder for generating SQL queries in one embodiment.\",\n \"FIG.\",\n \"4 depicts a graphical user interface (GUI) provided by a query builder in one embodiment.\",\n \"FIG.\",\n \"5 is a block diagram illustrating the details of a digital processing system in which several aspects of the present invention are operative by execution of appropriate executable modules.\",\n \"detailed-description description=\\\"Detailed Description\\\" end=\\\"lead\\\"?\",\n \"In the drawings, like reference numbers generally indicate identical, functionally similar, and/or structurally similar elements.\",\n \"The drawing in which an element first appears is indicated by the leftmost digit(s) in the corresponding reference number.\"\n ],\n [\n \"RELATED APPLICATIONS The present application is a continuation application of, and claims priority from, co-pending US Patent Application entitled, “DYNAMIC GENERATION OF DATABASE QUERIES IN QUERY BUILDERS”, application Ser.\",\n \"No.\",\n \"13/693,061, Filed: 4 Dec. 2012, and is incorporated in its entirety herewith.\",\n \"BACKGROUND OF THE INVENTION Technical Field The present disclosure relates to server systems, and more specifically to dynamic generation of database queries in query builders.\",\n \"Related Art Database queries refer to statements, which are used to access data in a database server.\",\n \"Queries are typically received from external systems, and the result of processing each query is sent as a response to the corresponding requesting external system.\",\n \"The queries may be received according to languages such as SQL (structured query language) well known in the relevant arts.\",\n \"A query builder refers to a utility, which facilitates non-technical users (e.g., business managers) to form database queries.\",\n \"In a typical implementation, a user merely provide various inputs required for forming desired conditions using a convenient GUI (graphical user interface), and the query builder then dynamically generates database queries containing the desired conditions based on the user provided inputs.\",\n \"The generated queries may be later executed for accessing the data matching the specific conditions, from a database server.\",\n \"Due to the use of such query builders, users may be shielded from various low level details such as syntax/semantics of language of the database queries (as specific to the database server), the underlying data organization (e.g., the specific tables and columns) in the database server, any required set-up for establishing connections with the database server, etc.\",\n \"It may be desirable to simplify generation of such database queries even when some of the low level details are changed (for example, when the underlying data is reorganized).\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS Example embodiments of the present invention will be described with reference to the accompanying drawings briefly described below.\",\n \"FIG.\",\n \"1 is a block diagram illustrating an example environment (computing system) in which several aspects of the present invention can be implemented.\",\n \"FIG.\",\n \"2 is a flowchart illustrating the manner in which a query builder generates database queries according to an aspect of the present invention.\",\n \"FIG.\",\n \"3 depicts a portion of a configuration data used by a query builder for generating SQL queries in one embodiment.\",\n \"FIG.\",\n \"4 depicts a graphical user interface (GUI) provided by a query builder in one embodiment.\",\n \"FIG.\",\n \"5 is a block diagram illustrating the details of a digital processing system in which several aspects of the present invention are operative by execution of appropriate executable modules.\",\n \"In the drawings, like reference numbers generally indicate identical, functionally similar, and/or structurally similar elements.\",\n \"The drawing in which an element first appears is indicated by the leftmost digit(s) in the corresponding reference number.\",\n \"DETAILED DESCRIPTION OF THE INVENTION 1.Overview A query builder provided according to an aspect of the present invention facilitates users to conveniently generate database queries directed to database servers storing data elements organized according to attributes.\",\n \"In an embodiment, configuration data indicating a comparison predicate to be used for each combination of an attribute and a conditional operation is maintained.\",\n \"A user may then provide as inputs a first attribute, a first conditional operation and a first value.\",\n \"In response, the query builder examines the configuration data to determine a first comparison predicate specified for the combination of the first attribute and the first conditional operation.\",\n \"The query builder incorporates the first value in the first comparison predicate to construct a second comparison predicate and then forms a first database query with the second comparison predicate.\",\n \"In one embodiment, the database server is implemented according to a relational database technology, with the query builder forming the first database query according to SQL (structured query language) as an SQL query.\",\n \"Several aspects of the present invention are described below with reference to examples for illustration.\",\n \"However, one skilled in the relevant art will recognize that the invention can be practiced without one or more of the specific details or with other methods, components, materials and so forth.\",\n \"In other instances, well-known structures, materials, or operations are not shown in detail to avoid obscuring the features of the invention.\",\n \"Furthermore, the features/aspects described can be practiced in various combinations, though only some of the combinations are described herein for conciseness.\",\n \"2.Example Environment FIG.\",\n \"1 is a block diagram illustrating an example environment (computing system) in which several aspects of the present invention can be implemented.\",\n \"The block diagram is shown containing network 110, database server 120, server system 130 (shown executing query builder 150) and end user systems 160A-160X.\",\n \"Merely for illustration, only representative number/type of systems is shown in FIG.\",\n \"1.Many environments often contain many more systems, both in number and type, depending on the purpose for which the environment is designed.\",\n \"Each system/device of FIG.\",\n \"1 is described below in further detail.\",\n \"Network 110 provides connectivity between server system 130 and end user systems 160A-160X, and may be implemented using protocols such as Transmission Control Protocol (TCP) and/or Internet Protocol (IP), well known in the relevant arts.\",\n \"In general, in TCP/IP environments, an IP packet is used as a basic unit of transport, with the source address being set to the IP address assigned to the source system from which the packet originates and the destination address set to the IP address of the target system to which the packet is to be eventually delivered.\",\n \"A (IP) packet is said to be directed to a target system when the destination IP address of the packet is set to the (IP) address of the target system, such that the packet is eventually delivered to the target system by network 110.When the packet contains content such as port numbers, which specifies the target application, the packet may be said to be directed to such application as well.\",\n \"Network 110 may be implemented using any combination of wire-based or wireless mediums.\",\n \"Database server 120 represents a non-volatile (persistent) storage facilitating storage and retrieval of a collection of data by one or more applications executing in server system 130 (typically while processing various client requests).\",\n \"In one embodiment, database server 120 is implemented using relational database technologies (that is, the data is organized in the form of tables and columns having corresponding names) and therefore provides storage and retrieval of data using structured queries such as SQL (Structured Query Language).\",\n \"As is well known, SQL refers to a special-purpose, generally non-procedural language that supports the definition, manipulation, and control of data in systems implementing relational database technologies.\",\n \"However, database server 120 can be implemented using other technologies (e.g., other languages, hierarchical databases) in alternative embodiments.\",\n \"A SQL query is generally of the form “SELECT columns FROM tables WHERE comparison predicate”, where SELECT, FROM and WHERE are keyword in SQL, columns is a list of columns to be included in the result (with an asterisk (“*”) indicating all columns), tables is a list of tables from which data is to be retrieved, and comparison predicate is a logical condition used to restrict the rows returned by the query.\",\n \"The comparison predicate typically contains one or more conditions (combined by logical operators such as AND, OR, NOT), with each condition specifying a column name (in a table), a comparison operator (such as “=”, “LIKE”, “IN”, etc.)\",\n \"and a value to be compared with.\",\n \"In addition, the SQL query may contain a GROUP BY clause for grouping rows based on specified columns, a HAVING clause specifying a predicate used to filter rows resulting from the GROUP BY clause, and a ORDER BY clause for specifying the order of rows in the result.\",\n \"Each of end user systems 160A-160X represents a system such as a personal computer, workstation, mobile station, mobile phone, computing tablet, etc., used by users to generate (client) requests directed to applications executing in server system 130.The requests may be generated using appropriate user interfaces provided by applications executing in server system 130 or in the end user system.\",\n \"In general, a user sends client requests for performing desired tasks and receives corresponding responses containing the results of performance of the requested tasks.\",\n \"Each request is sent in the form of an IP packet directed to server system 130 (and corresponding application), with the IP packet including data identifying the desired tasks in the payload portion.\",\n \"Server system 130 represents a system such as a web/application server executing applications capable of performing tasks requested by users.\",\n \"In response to receiving a client requests from an end user system (such as 160A-160X), an application (to which the client request is directed to) executing in server system 130 performs the tasks specified in the request and sends the result of performance of the tasks to the requesting end user system.\",\n \"The application may use data stored internally (for example, in a non-volatile storage/hard disk within the server system), external data (for example, in database server 120) and/or data received from external sources (e.g., from the user) in performing such tasks.\",\n \"Query builder 150 facilitates non-technical users using end user systems 160A-160X to dynamically create SQL queries for retrieving data from database server 120.Query builder 150 provides a graphical user interface (GUI) on an end user system (such as 160A-160X) that enables a user to provide various inputs for forming desired conditions (using the GUI).\",\n \"Query builder 150 then generates SQL queries based on the user provided inputs.\",\n \"The generated SQL queries may then be executed (either by query builder 150 or by a different module/application, not shown) or stored for later execution.\",\n \"In the following disclosure, query builder 150 is assumed to be a stand-alone block/application executing in server system 130.However, in alternative embodiments, query builder 150 may be implemented within an application executing in server system 130, as an external module such as a Dynamic-link library (DLL) that is used/shared by multiple applications executing in server system 130 or an application utility executing in one of the end user systems.\",\n \"The features of the present invention can be implemented in such alternative embodiments as well, as will be apparent to one skilled in the relevant arts by reading the disclosure herein.\",\n \"The manner in which query builder 150 dynamically generates SQL queries based on user provided inputs according to several aspects of the present invention is described below with examples.\",\n \"3.Generating Database Queries FIG.\",\n \"2 is a flowchart illustrating the manner in which a query builder generates database queries according to an aspect of the present invention.\",\n \"The flowchart is described with respect to FIG.\",\n \"1, and in relation to query builder 150 merely for illustration.\",\n \"However, the features can be implemented in other environments (and in other servers) also without departing from the scope and spirit of various aspects of the present invention, as will be apparent to one skilled in the relevant arts by reading the disclosure provided herein.\",\n \"In addition, some of the steps may be performed in a different sequence than that depicted below, as suited to the specific environment, as will be apparent to one skilled in the relevant arts.\",\n \"Many of such implementations are contemplated to be covered by several aspects of the present invention.\",\n \"The flow chart begins in step 201, in which control immediately passes to step 210.In step 210, query builder 150 maintains a configuration data indicating a comparison predicate to be used for each combination of a stored attribute and conditional operation of interest.\",\n \"An (stored) attribute provides a common name for a group of data elements (that are stored in the database) sharing a characteristic.\",\n \"In case of relational databases, a stored attribute eventually maps to a column of a table of a stored relational database.\",\n \"Evaluation of a conditional operation against data items results in a logical result.\",\n \"The conditional operation can be any of comparison operations (less than, equal to, between, etc.\",\n \"), state operations (exists, missing, contained in, begins with, etc).\",\n \"As noted above, a comparison predicate (specified as part of a SQL query) ensures that only the rows in the tables for which the comparison predicate evaluates to true are included in the result of processing of a corresponding SQL query.\",\n \"The configuration data may be maintained in a persistent storage such as database server 120.The configuration data may be specified by developers of the query builder and/or applications executing in server system 130 or by administrators of server system 130.In step 230, query builder 150 receives, from a user, a stored attribute, a conditional operation of interest, and a value (hereafter together referred to as a “conditional expression”).\",\n \"The conditional expression may be received from one of developer systems 160A-160X, in response to the user specifying the three inputs using a graphical user interface provided on the developer system by query builder 150.In step 250, query builder 150 determines the comparison predicate for the received combination of stored attribute and conditional operation.\",\n \"The determination is performed by examining the configuration data, after retrieval from the persistent storage, and may be performed in a known way.\",\n \"For example, query builder 150 may first identify a combination in the configuration data the received stored attribute and conditional operations, and then determine the comparison predicate associated with the identified combination.\",\n \"In step 270, query builder 150 incorporates the received value in the determined comparison predicate.\",\n \"According to a convention described below, the comparison predicate in the configuration data includes place holders for values to be specified by the users.\",\n \"Incorporation in such convention therefore entails replacing the place holders with the corresponding user provided values.\",\n \"Query builder 150 may perform any appropriate conversions of the received value before performing such replacements.\",\n \"In step 290, query builder 150 forms a database query with the incorporated comparison predicate, for example, as the WHERE clause of a SQL query.\",\n \"The columns and tables (in the FROM clause) may be determined by query builder 150 by inspecting the comparison predicate.\",\n \"Alternatively, the configuration data may be designed to also indicate (in addition to the comparison predicate) the specific columns/tables to be included in the SQL query.\",\n \"As noted above, the formed SQL query may be executed or stored for later execution.\",\n \"The flow chart ends in step 299.Thus, query builder 150 dynamically generates SQL queries based on user provided inputs.\",\n \"It should be noted that the steps of 230, 250 and 270 can be iterated by a user to specify a complex condition having multiple conditional expressions.\",\n \"The step of 290 may be performed only after the user has specified the desired set of conditional expressions.\",\n \"It may be appreciated that any changes required to SQL queries in view of situations such as changes to the business logic (such as the manner of retrieval) and/or the organization of data (such as the structures of the tables/columns), can be effected by modifying the comparison predicates in the configuration data (in view of the techniques described above).\",\n \"The programming logic for the generation of the SQL query embedded within (the instructions constituting) query builder 150 need not accordingly be modified in response to such changes.\",\n \"The manner in which query builder 150 dynamically generates SQL queries according to the foregoing description, is illustrated below with examples.\",\n \"4.Illustrative Example FIGS.\",\n \"3 and 4 together illustrate the manner in SQL queries are dynamically generated in query builders (in particular, query builder 150) in one embodiment.\",\n \"Each of the Figures is described in detail below.\",\n \"FIG.\",\n \"3 depicts a portion of a configuration data used by a query builder (150) for generating SQL queries in one embodiment.\",\n \"For illustration, the configuration data is shown maintained in the form of a table (300) in database server 120.However, in alternative embodiments, the configuration data may be maintained using other data formats such as extensible markup language (XML), as will be apparent to one skilled in the relevant arts by reading the disclosure herein.\",\n \"Table 300 depicts portions of configuration data maintained by query builder 150.In particular, columns 321 “Attribute” and 322 “Condition” specifies a combination of the (name of) a stored attribute and a conditional operation, while columns 323 “Table” and 324 “Predicate” respectively specifies the table and comparison predicate for the corresponding combination.\",\n \"Thus, each of rows 341-346 specifies the corresponding table and comparison predicate to be used for a combination of stored attribute and conditional operation.\",\n \"For example, row 341 indicates that the table “V_RPT_PRODUCT’ table is to be included in the FROM clause and the predicate “V_RPT_CASE.CASE_ID=V_RPT_PRODUCT.CASE_ID and V_RPT_PRODUCT.PRODUCT_ID=(select PRODUCT ID from V_DRUG_NAME where upper(PRODUCT_NAME)=upper(‘#PARAM#’))” is to be used in the WHERE clause for the combination of the stored attribute “Company Product” and conditional operation “Equal to”.\",\n \"It may be observed that the predicate contains the text “#PARAM#” indicating a place holder for a (user provided) value to be later incorporated.\",\n \"Similarly other rows 342-346 specify the table and predicate to be used for corresponding combinations.\",\n \"In the following description it is assumed that all the generated SQL queries retrieve the values in the default table/column “V_RPT_CASE.case_id” and that the default table “V_RPT_CASE” is to be included in the FROM clause in addition to the tables specified in column 423.However, in alternative embodiments, the specific columns to be retrieved and the specific tables to be used may be specified as part of configuration data (table 300), as will be apparent to one skilled in the relevant arts.\",\n \"It may be appreciated that the configuration data indicates that different predicates are to be used for different combinations of stored attributes and conditional operations.\",\n \"The predicates may be specified by a developer/administrator based on the underlying business logic (for example, how are company products to be retrieved in relation to cases) to be used, the data organization (tables V_RPT_CASE, V_RPT_REPORT) in database server 120, any optimizations that can be performed during retrieval, etc.\",\n \"In a scenario that there is a change in the business logic or data organization, the developer/administrator is required to only modify the predicates in column 324 of table 300, with query builder 150 then using the modified predicates for the generation of the SQL queries.\",\n \"Thus, query builder 150 maintains configuration data (300) indicating the specific comparison predicates to be used for each combination of stored attribute and conditional operation.\",\n \"Query builder 150 then generates SQL queries based on such configuration data (300) and user provided inputs.\",\n \"The manner in which a user is enabled to provide inputs for generating SQL queries is described below with examples.\",\n \"5.Graphical User Interface FIG.\",\n \"4 depicts a graphical user interface (GUI) provided by a query builder (150) in one embodiment.\",\n \"Display area 400 depicts a portion of a user interface provided on a display unit (not shown in FIG.\",\n \"1) associated with one of end user systems (assumed to be 160A, for illustration).\",\n \"In one embodiment, display area 400 corresponds to a browser (as indicated by the text in display area 405) displaying a web page provided by query builder 150, in response to a user sending a request from end user system 160A.\",\n \"Display area 420 enables a user to create a new query (advanced condition) by clicking the “Create Query” button and to view the results of executing previously created queries by clicking the “Query Results” button.\",\n \"The description is continued assuming that the user has selected the “Create Query” button to specify a new query.\",\n \"Display area 440 enables to user to name and save the newly created query, thereby enabling the user to later execute the saved query.\",\n \"The text “” in display area 440 indicates that the user has not yet named/saved the current query.\",\n \"Display area 450 enables the user to provide various inputs for forming desired conditional expressions.\",\n \"In particular, the user specifies a stored attribute (by selecting or entering the name in the “Attribute” column), a conditional operation (by selecting from the options provided in “Condition” column), and a value to be used for comparison (by searching for or entering in the “Value” column).\",\n \"The user may also combine multiple conditional expressions using logical operators such as AND, OR, AND NOT, etc.\",\n \"(by selecting the appropriate option in the “Operator” column).\",\n \"It may be observed that each of the conditional expressions is specified in a corresponding row (such as row 475) in display area 470.A user may select the buttons shown in display area 460 for adding new rows/conditions or removing older rows/conditions from display area 470.For example, a user may click/select the buttons labeled with a “+” in display area 460 to add a row (either before or after the currently selected row indicated by the dotted boundary, i.e., row 475) in display area 470, and may click/select the button labeled with a “x” in display area 460 to remove the currently selected row (i.e., row 475).\",\n \"It may be appreciated that the conditional expressions specified in the set of rows in display area 470 represents a complex conditional expression based on which the SQL query is sought to be generated.\",\n \"A user may also select the opening bracket “(” and closing bracket “)” columns to specify sub-expressions in the complex conditional expression in display area 370.An example of such a complex conditional expression having sub-expressions is “Report Type equal to Spontaneous AND (Country equal to United States OR Country equal to Australia)”, where Report Type and Country are specified in the “Attribute’ column; “equal to” is specified in the “Condition’ column; Spontaneous, United States and Australia are specified in the ‘Value’ column; “AND” and “OR” are specified in the ‘Operator’ column; and the opening and closing brackets are selected in the appropriate “(” and “)” columns.\",\n \"Thus, a user using the user interface of FIG.\",\n \"3 is facilitated to specify various inputs for forming the desired conditions/conditional expression.\",\n \"The description is continued assuming that the user has specified the one conditional expression in the form “Company Product”, “Equal to” and “Vovern [Capsule, 500 mg]” shown in display area 470.The user may then (after specifying a name using an interface not shown) click/select the “Save” button in display area 480 to indicate that a SQL query is to be generated (based on the specified conditional expression) and stored for later execution.\",\n \"Alternatively, the user may click on “Execute” button in display area 480 to indicate that a SQL query is to be generated and immediately executed.\",\n \"In response to a user selecting the Save or Execute buttons, query builder 150 generates a SQL query based on the conditions/inputs specified by the user in display area 470.In the embodiment noted above, the browser sends the inputs specified in display area 470 in the form of IP packets directed to server system 130 (in particular query builder 150).\",\n \"Query builder 150 then generates the SQL query in response to receiving the IP packets from the browser.\",\n \"The manner in which query builder 150 generates/forms a SQL query based on the user provided inputs (of display area 470) and configuration data (300) is described below with examples.\",\n \"6.Generating a SQL Query In response to receiving the user inputs “Company Product”, “Equal to” and “Vovern [Capsule, 500 mg]”, query builder 150 first examines configuration data 300 to determine the comparison predicate for the received combination of stored attribute “Company Product” and conditional operation “Equal to”.\",\n \"Query builder 150 may accordingly identify that row 341 corresponds to the received combination and that predicate indicated in column 324 of row 341 is to be used in the SQL query.\",\n \"Query builder 150 then incorporates the received value in the determined predicate by replacing the one occurrence of the text “#PARAM#” in the determined predicate with the received value “Vovern [Capsule, 500 mg]”.\",\n \"Query builder 150 then forms the SQL query by using the default column “V_RPT_CASE.case id”, the tables “V RPT CASE” (default table) and “V_RPT_PRODUCT” (the value in column 323 of row 341) in the FROM clause and the incorporated predicate in the WHERE clause.\",\n \"Thus, query builder 150 may form the below noted query in response to receiving the values shown in display area 470: SELECT_DISTINCT_V_RPT_CASE.\",\n \"case id FROM V_RPT_CASE, V_RPT_PRODUCT WHERE (V_RPT_CASE.CASE_ID=V_RPT_PRODUCT.\",\n \"CASE_ID and V_RPT_PRODUCT.PRODUCT_ID=(select PRODUCT_ID from V_DRUG_NAME where upper(PRODUCT_NAME)=upper(‘Vovern [Capsule, 500 mg]’)) Thus, query builder 150 generates a SQL query based on user provided inputs (shown in display area 470) and configuration data (300).\",\n \"Query builder 150 may then execute or store (based on whether the user selected “Execute” button or “Save” button in display area 480) the above generated SQL query.\",\n \"In a scenario that a complex condition (having multiple conditional expressions) is specified by the user in display area 470, query builder 150 may first identify the predicates for each of the combinations in the multiple conditional expressions, incorporate the values specified in the corresponding conditional expressions in the determined predicates and then combine the incorporated predicates based on the logical operators (AND, OR, etc.)\",\n \"specified by the user.\",\n \"The SQL query may then be formed using the combined predicate corresponding to all the conditional expressions in the complex condition.\",\n \"Furthermore, query builder 150 may also receives data indicating sub-expressions and process them by adding corresponding sub-expressions in the generated SQL query.\",\n \"It should be appreciated that though several features of the present invention are described above with respect to the “SELECT” SQL statement, in alternative embodiments, the features of the present invention may be implemented in the context of other types of conditional SQL statements (such as INSERT, UPDATE and DELETE) as well, as will be apparent to one skilled in the relevant arts by reading the disclosure herein.\",\n \"It should be further appreciated that the features described above can be implemented in various embodiments as a desired combination of one or more of hardware, executable modules, and firmware.\",\n \"The description is continued with respect to an embodiment in which various features are operative when corresponding executable modules are executed.\",\n \"7.Digital Processing System FIG.\",\n \"5 is a block diagram illustrating the details of digital processing system 500 in which several aspects of the present invention are operative by execution of appropriate executable modules.\",\n \"Digital processing system 500 may correspond to any system (such as server system 130) executing query builder 150 or any one of end user systems 160A-160X.\",\n \"Digital processing system 500 may contain one or more processors (such as a central processing unit (CPU) 510), random access memory (RAM) 520, secondary memory 530, graphics controller 560, display unit 570, network interface 580, and input/ output interface 590.All the components except display unit 570 may communicate with each other over communication path 550, which may contain several buses as is well known in the relevant arts.\",\n \"CPU 510 may execute instructions stored in RAM 520 to provide several features of the present invention.\",\n \"CPU 510 may contain multiple processing units, with each processing unit potentially being designed for a specific task.\",\n \"Alternatively, CPU 510 may contain only a single general-purpose processing unit.\",\n \"RAM 520 may receive instructions from secondary memory 530 using communication path 550.RAM 520 is shown currently containing software instructions constituting shared environment 525 and/or user programs 526.Shared environment 525 contains utilities shared by user programs, and such shared utilities include operating systems, virtual machines, etc., which provide a (common) run-time environment for execution of user programs 526 (such as browsers, email client software).\",\n \"Graphics controller 560 generates display signals (e.g., in RGB format) to display unit 570 based on data/instructions received from CPU 510.Display unit 570 contains a display screen to display the images defined by the display signals (for example, portions of the user interface shown in FIG.\",\n \"4).\",\n \"Input/output interface 590 includes input as well as output devices to enable a user to interact with system 500 (for example, to interact with the user interface of FIG.\",\n \"4 such as selecting the desired stored attributes, conditional operations, specifying values).\",\n \"Network interface 580 provides the physical, electrical and protocol implementations that enable system 500 to communicate with other systems of FIG.\",\n \"1 using protocols such as TCP/IP.\",\n \"Secondary memory 530 (representing a non-transitory storage/medium) may contain hard drive 535, flash memory 536, and removable storage drive 537.Secondary memory 530 may store data (for example, portions of configuration data shown in FIG.\",\n \"3, portions of the user provided inputs, portions of the generated SQL queries) and software instructions (for example, for performing the steps of FIG.\",\n \"2), which enable digital processing system 500 to provide several features in accordance with the present invention, as described above.\",\n \"Some or all of the data and instructions may be provided on removable storage unit 540, and the data and instructions may be read and provided by removable storage drive 537 to CPU 510.Floppy drive, magnetic tape drive, CD-ROM drive, DVD Drive, Flash memory, removable memory chip (PCMCIA Card, EPROM) are examples of such removable storage drive 537.Removable storage unit 540 may be implemented using medium and storage format compatible with removable storage drive 537 such that removable storage drive 537 can read the data and instructions.\",\n \"Thus, removable storage unit 540 includes a computer readable storage medium having stored therein computer software and/or data.\",\n \"However, the computer (or machine, in general) readable storage medium can be in other forms (e.g., non-removable, random access, etc.).\",\n \"In this document, the term “computer program product” is used to generally refer to secondary memory 530.These computer program products are means for providing software to digital processing system 500.CPU 510 may retrieve the software instructions, and execute the instructions to provide various features of the present invention described above.\",\n \"It should be understood that numerous specific details, relationships, and methods are set forth to provide a full understanding of the invention.\",\n \"For example, many of the functions units described in this specification have been labeled as modules/blocks in order to more particularly emphasize their implementation independence.\",\n \"Reference throughout this specification to “one embodiment”, “an embodiment”, or similar language means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention.\",\n \"Thus, appearances of the phrases “in one embodiment”, “in an embodiment” and similar language throughout this specification may, but do not necessarily, all refer to the same embodiment.\",\n \"Furthermore, the described features, structures, or characteristics of the invention may be combined in any suitable manner in one or more embodiments.\",\n \"In the above description, numerous specific details are provided such as examples of programming, software modules, user selections, network transactions, database queries, database structures, hardware modules, hardware circuits, hardware chips, etc., to provide a thorough understanding of embodiments of the invention.\",\n \"8.Conclusion While various embodiments of the present invention have been described above, it should be understood that they have been presented by way of example only, and not limitation.\",\n \"Thus, the breadth and scope of the present invention should not be limited by any of the above-described exemplary embodiments, but should be defined only in accordance with the following claims and their equivalents.\",\n \"It should be understood that the figures and/or screen shots illustrated in the attachments highlighting the functionality and advantages of the present invention are presented for example purposes only.\",\n \"The present invention is sufficiently flexible and configurable, such that it may be utilized in ways other than that shown in the accompanying figures.\",\n \"Further, the purpose of the following Abstract is to enable the Patent Office and the public generally, and especially the scientists, engineers and practitioners in the art who are not familiar with patent or legal terms or phraseology, to determine quickly from a cursory inspection the nature and essence of the technical disclosure of the application.\",\n \"The Abstract is not intended to be limiting as to the scope of the present invention in any way.\"\n ]\n]"},"source":{"kind":"string","value":"Patent_15871998"}}},{"rowIdx":4493979,"cells":{"text":{"kind":"list like","value":[["Mechanical energized sealing ball valve","The invention relates to a mechanical energized sealing ball valve comprising a seat, a ball assembly, and a single valve stem that operates both the sealing member and the ball.","The ball comprises a ball and a sealing member.","The valve stem drives the ball to rotate between open position and close position.","When the ball reaches the close position, the sealing member, operated by the same valve stem, moves away from the ball to press and sit against the seat.","The invention has the advantages that: the valve has a compact structure, the friction-free on/off is achieved, the mechanical energized sealing force is even and reliable, the ball is retracted and locked in the opening position to protect against turbulence-induced damage, low operating torque, the open/close operation is rapid, and the valve stem seal operates simply and reliably."],["1.A ball valve with single-action actuation and sealing, the ball valve comprising: a ball assembly, the ball assembly including a ball and a sealing member, the ball assembly having an open position and a closed position; a first valve stem, the first valve stem causing both rotation of the ball and motion of the sealing member; a valve seat; wherein when the ball assembly is in the open position, rotation of the first valve stem first rotates the ball to the closed position, and then causes the sealing member to move linearly towards the valve seat causing the sealing member to press against the valve seat.","2.The ball valve of claim 1, wherein the first valve stem is mechanically coupled to the sealing member using a first gear, a second gear, and a third gear.","3.The ball valve of claim 1, wherein the first gear is coaxial with the first valve stem, and the third gear is coaxial with the sealing member.","4.The ball valve of claim 1, wherein the first valve stem is mechanically coupled to the ball by means of a spring.","5.The ball valve of claim 1, wherein a lower trunnion of the ball is provided with a 90° fan-shaped projection, and a lower trunnion chamber of a valve body is provided with a 180° limiting slot.","6.A ball valve with sequential ball actuation and seal actuation using a single valve stem, the ball valve comprising: a ball, the ball having an open position and a closed position, the ball actuated by the single valve stem during a closure operation; a sealing surface, the sealing surface moving inward and outward with respect to the ball, the sealing surface actuated by the single valve stem during a sealing operation; the sealing surface pressing against a seat when in a sealed position; the closure operation and sealing operation being automatically sequenced depending upon the position of the ball; wherein when the ball is in an open position, rotation of the single valve stem causes the closure operation to occur, and upon the ball reaching a closed position, the single valve stem then causes the sealing operation to occur; wherein when the ball is in a closed position, rotation of the single valve stem causes the sealing operation to occur, and upon the ball reaching an open position, the single valve stem then causes the closure operation to occur.","7.The ball valve of claim 6, wherein the single valve stem is mechanically coupled to the sealing surface using a first gear, a second gear, and a third gear.","8.The ball valve of claim 7, wherein the first gear is coaxial with the single valve stem, the third gear is coaxial with the sealing surface.","9.The ball valve of claim 6, wherein the single valve stem is mechanically coupled to the ball by means of a spring.","10.The ball valve of claim 6, wherein a lower trunnion of the ball is provided with a 90° fan-shaped projection, and a lower trunnion chamber of a valve body is provided with a 180° limiting slot.","11.A mechanical energized sealing ball valve, comprising: a seat; a ball assembly; and a single valve stem, the single valve stem independent of any other valve stem; wherein the ball assembly comprises a ball and a sealing member; the single valve stem rotating the ball and operating the sealing member; wherein rotation of the single valve stem first causes the ball to rotate between an open position and a closed position, and when the ball reaches the closed position, the continued rotation of the valve stem presses the sealing member against the seat.","12.The mechanical energized sealing ball valve according to claim 11, wherein a thread driving wheel is disposed on the ball and connected with the sealing member through threads, and the thread driving wheel causes the sealing member to move inwardly and outwardly.","13.The mechanical energized sealing ball valve according to claim 12, wherein the valve stem causes the thread driving wheel to rotate.","14.The mechanical energized sealing ball valve according to claim 12, wherein the thread driving wheel is cut with gear teeth, and the single valve stem causes the thread driving wheel to rotate by way of a sealing driving gear.","15.The mechanical energized sealing ball valve according to claim 14, wherein an intermediate transmission gear is disposed between the thread driving wheel and the sealing driving gear.","16.The mechanical energized sealing ball valve according to claim 11 wherein when the ball rotates to the closed position from the open position, the ball stops rotating and the single valve stem continues rotating towards the closing direction, causing the sealing member to sit against the seat.","17.The mechanical energized sealing ball valve according to claim 11, wherein a lower trunnion of the ball is provided with a 90° fan-shaped projection, and a lower trunnion chamber of a valve body is provided with a 180° limiting slot.","18.The mechanical energized sealing ball valve according to claim 11, wherein the single valve stem drives the ball to rotate using an elastic component.","19.The mechanical energized sealing ball valve according to claim 18, wherein the elastic component is a torsion spring.","20.The mechanical energized sealing ball valve according to claim 18, wherein the elastic element applies a pre-driving force to the ball for rotating the ball towards the closing position."],[" BACKGROUND In the flow control application, for example, oil/gas production process switching, pipeline shut-off, metering, pressure regulation, molecular sieve switching, compressor inlet/outlet, hydrogen application in oil refining process, air separation of synthetic ammonia equipment, and the like, which require frequent operation and have strict requirements on flow on-off control and closing tightness, it is desired that valves produce a pressure drop as small as possible and can provide a forced torque seal without the influence of the pressure of fluid within the pipeline.","Mechanical energized sealing ball valves are recognized as an ideal solution.","However, for the conventional rising stem mechanical energized sealing ball valve, although there is no contact or friction between the ball and the seat during most of the opening/closing stroke, sliding friction exists between the ball and seat sealing area during the final ball-seat engagement stage.","Thus, valve operation is not a true friction-free rotation, and the ball against seat sealing relies on the stem wedging against ball, with ball being held by lower trunnion.","As a result the movement is unsteady and susceptible to the influence of tolerance of the relative position of the seat and the lower trunnion.","Additionally, the valve stem portion and its assembly have a complicated structure and require the combination of linear movement and rotation movement during the opening/closing process.","The requirement for machining precision is strict, the risk of valve stem leakage is high, and the time of opening/closing operation is too long.","The following six documents of mechanical energized sealing ball valve are found by SIPO patent inquiry: Publication No.","CN104295764A, Application No.","2014105008955: Disclosed is a valve that opens or close using a valve stem and a ball in eccentric arrangement and synchronous rotation.","The design is essentially a modification of eccentric butterfly valve, in which a relative sliding friction between seat and ball sealing surface is produced due to a large angular stroke vector existing during the final siting stage of the ball and seat.","Thus, it is not a true friction-free rotation, as the closing operation is an angular stroke, and the resulting normal component of force between the ball and the seat is not large, which may impact the sealing reliability and actual service life.","Publication No.","CN103727260A, Application No.","2014100163761: Disclosed is a ball valve, in particular a mechanical energized sealing ball valve, comprising a valve body, a secondary valve body, a ball, a seat, and a secondary valve body fluid port, and a stud-nut-driving-type mechanical energized sealing device disposed on the shell of the secondary valve body fluid port.","The worm wheel and the driving stud are coupled via a flat key, when the driving stud makes a rotational movement, the axial sliding key groove of the driven nut fits the driving stud in a rotating manner, enabling an axial linear movement along the guide key on the secondary valve body fluid port.","As a result, a desired sealing specific pressure is generated between the seat and the ball within the valve cavity by the pressure generated outside the body through a pressure transfer system, thereby low-torque opening/closing and mechanical energized sealing can be achieved, and the interlinked actuation of the stud-nut energized sealing device and the electric actuator during opening/closing and sealing process are completed through an automatic control system.","The design applies two operating mechanisms, one of them operates the ball to rotate 90 degrees, and the other operates the said secondary valve body for driving the seat to sit against ball.","The design has many potential leakage paths, complicated structure and bulky size, and is not able to meet standard valve face-to-face dimensions.","Publication No.","CN103527809A, Application No.","2013105342621: Disclosed is a valve comprising a valve body, a valve bonnet , a valve stem, a wedged plug and sealing members, characterized in that the top of the valve body is connected with the valve bonnet, the valve stem is vertically mounted in the center of the top of the valve body through a support, the wedged plug in the cavity of the valve body is fixed at the bottom of the valve stem by a pin through a hole in the center of the valve bonnet to synchronize the movement of the valve stem and the wedged plug, that is, rotating and raising aligned to a fixed axis.","A fixed shaft is perpendicularly disposed in the bottom center of the cavity, the fixed shaft is matched with a hole in the bottom center of the wedged plug, the valve sealing members are fixed at the two sides of the bottom of the cavity through T-shaped grooves, valve sealing member stops are disposed on the top of the valve sealing member and on the inner walls of the two sides of the cavity, and the valve sealing member stops on the two sides are firmly connected with the two side walls of the wedged plug.","The design is actually a mechanical energized plug valve (also known as DBB plug valve in the industry), although the valve can achieve mechanical energized sealing in a closed position, owing to the sliding-type sealing member configuration, the valve sealing member to be influenced by the turbulence when the valve is in the open position.","At present, the design is used for applications under low pressure liquid working conditions only.","Publication No.","CN102979929A, Application No.","2012105315085: Disclosed is a valve comprising a ball, a seat and a sealing ring seat disposed between the ball and the seat to perform the sealing, and a hydraulic device for pushing the sealing ring seat in the axial direction of the sealing ring seat, the hydraulic device being disposed between the seat and the sealing ring seat.","The design realizes a forced seal by applying a pressure to the seal ring between the seat and the ball by using a set of hydraulic system, but the hydraulic leakage and complicated structure of the valve may affect the sealing reliability and service life of the valve.","Publication No.","CN105370909A, Application No.","2014104406033: Disclosed is an opening/closing part having two eccentric spherical members.","Such eccentric structure allows each of the two eccentric spherical surfaces to make a movement in the axial direction of the downstream seat and the upstream seat when the valve stem drives the opening/closing part to make a rotational movement, resulting in the effect of compressing or releasing the seat, thereby realizing the forced seal of the opening/closing part relative to the downstream seat and the upstream seat in a particular valve position.","The valve of the design may be influenced by turbulence in the opening position, the two eccentric spherical members may be damaged by turbulence vibration, which affects the reliability and service life of the valve.","Publication No.","CN104132157A, Application No.","2013101575904: Disclosed is a forced seal valve based on modular design and angular stroke operation, mainly comprising a valve body, an opening/closing part, a valve bonnet, a valve stem, a seat, a flow guide barrel, a seat support plate, a flow guide barrel support plate, an operating mechanism and a drainage valve.","The opening/closing part is arranged between the seat and the flow guide barrel, by adjusting the relative position of sphere center and radii of the convex spherical surface and center of the concave spherical surface, the thicknesses of individual portions of the opening/closing part can be adjusted to adjust the sealing specific pressure between the opening/closing part and the seat when the valve is located in different valve positions, so that the valve realizes a forced seal in a certain valve position.","Accordingly, the design is not a mechanical energized sealing ball valve in a whole sense."],[" SUMMARY An object of the invention is to provide a technical solution of mechanical energized sealing ball valve, thus improving the operating performance and sealing tightness of the ball valve.","In order to achieve the above purpose, the technical solution adopted by the invention is as follows: A mechanical energized sealing ball valve, comprising a seat, a ball assembly and a valve stem, characterized in that the ball assembly comprises a ball and a sealing member, the valve stem drives the ball to rotate between open position and close position, when the ball reaches the close position, the sealing member jacks-up of the ball to sit against the seat.","The ball is driven open and closed, and the sealing member sealed and unsealed, using a single valve stem.","This is in contrast to the prior art, where two or more valve stems were required for the separate operations of opening or closing the ball, and moving the sealing member toward or away from a seat.","Furthermore, a thread driving wheel is disposed on the ball and connected with the sealing member through threads, and the thread driving wheel jacks and retracts the sealing member through the threads during rotating.","Furthermore, the valve stem drives the thread driving wheel to rotate.","Furthermore, the thread driving wheel is cut with gear teeth, and the valve stem drives the thread driving wheel to rotate through a sealing driving gear.","Furthermore, an intermediate transmission gear is disposed between the thread driving wheel and the sealing driving gear.","These gears are alternatively referred to as a first, second, and third gear.","Furthermore, the sealing member and the ball are engaged by means of linear movement.","Furthermore, when the ball rotates to the close position from the open position, the ball stops rotating and the valve stem continues rotating towards the closing direction, so that the sealing member sits against the seat.","The sealing member is alternatively referred to as a sealing surface.","Furthermore, the rotation stroke of the ball is 90°.","Furthermore, the lower trunnion of the ball is provided with a 90° fan-shaped projection, and the lower trunnion chamber of the valve body is provided with a 180° limiting slot.","Furthermore, the valve stem drives the ball to rotate through an elastic component.","Furthermore, the elastic component is a torsion spring.","Furthermore, a torsion spring shaft is disposed at the bottom of the valve stem, with the torsion spring being sleeved on the torsion spring shaft, and the valve stem and the ball are respectively provided with torsion spring pin holes, with the torsion spring pins of the torsion spring being embedded into the torsion spring pin holes of the valve stem and the ball.","Furthermore, the elastic element applies to the ball a pre-driving force for rotating the ball towards the closing position.","Furthermore, the sealing member retracts towards the ball and contacts the ball during the opening process of the mechanical energized sealing ball valve.","The invention has the advantages that: the valve has a compact structure, the true sealing friction-free face in both open and close operation, the sealing force is even and reliable, the ball assembly is retracted and locked in the opening position to protect against turbulence-induced damage, the moment of ball valve operating torque is small, the open/close operation is rapid, and the valve stem seal is simple and reliable.","The invention will now be described in detail with reference to the accompanying drawings and examples."],["CROSS-REFERENCE TO RELATED APPLICATION This application is a continuation of U.S. patent application Ser.","No.","15/678,507, filed Aug. 16, 2017, titled “A mechanical energized sealing ball valve”, which is in turn a continuation of PCT application number PCT/CN2017/080179, filed Apr.","12, 2017, title translated as “Forced Sealing Ball Valve,” which in turn claims priority to China application number ZL 2016 20491127.2, filed May 26, 2016, title translated as “Forced Sealing Ball Valve.” FIELD The invention is a ball valve, and in particular a mechanical energized sealing ball valve.","BACKGROUND In the flow control application, for example, oil/gas production process switching, pipeline shut-off, metering, pressure regulation, molecular sieve switching, compressor inlet/outlet, hydrogen application in oil refining process, air separation of synthetic ammonia equipment, and the like, which require frequent operation and have strict requirements on flow on-off control and closing tightness, it is desired that valves produce a pressure drop as small as possible and can provide a forced torque seal without the influence of the pressure of fluid within the pipeline.","Mechanical energized sealing ball valves are recognized as an ideal solution.","However, for the conventional rising stem mechanical energized sealing ball valve, although there is no contact or friction between the ball and the seat during most of the opening/closing stroke, sliding friction exists between the ball and seat sealing area during the final ball-seat engagement stage.","Thus, valve operation is not a true friction-free rotation, and the ball against seat sealing relies on the stem wedging against ball, with ball being held by lower trunnion.","As a result the movement is unsteady and susceptible to the influence of tolerance of the relative position of the seat and the lower trunnion.","Additionally, the valve stem portion and its assembly have a complicated structure and require the combination of linear movement and rotation movement during the opening/closing process.","The requirement for machining precision is strict, the risk of valve stem leakage is high, and the time of opening/closing operation is too long.","The following six documents of mechanical energized sealing ball valve are found by SIPO patent inquiry: Publication No.","CN104295764A, Application No.","2014105008955: Disclosed is a valve that opens or close using a valve stem and a ball in eccentric arrangement and synchronous rotation.","The design is essentially a modification of eccentric butterfly valve, in which a relative sliding friction between seat and ball sealing surface is produced due to a large angular stroke vector existing during the final siting stage of the ball and seat.","Thus, it is not a true friction-free rotation, as the closing operation is an angular stroke, and the resulting normal component of force between the ball and the seat is not large, which may impact the sealing reliability and actual service life.","Publication No.","CN103727260A, Application No.","2014100163761: Disclosed is a ball valve, in particular a mechanical energized sealing ball valve, comprising a valve body, a secondary valve body, a ball, a seat, and a secondary valve body fluid port, and a stud-nut-driving-type mechanical energized sealing device disposed on the shell of the secondary valve body fluid port.","The worm wheel and the driving stud are coupled via a flat key, when the driving stud makes a rotational movement, the axial sliding key groove of the driven nut fits the driving stud in a rotating manner, enabling an axial linear movement along the guide key on the secondary valve body fluid port.","As a result, a desired sealing specific pressure is generated between the seat and the ball within the valve cavity by the pressure generated outside the body through a pressure transfer system, thereby low-torque opening/closing and mechanical energized sealing can be achieved, and the interlinked actuation of the stud-nut energized sealing device and the electric actuator during opening/closing and sealing process are completed through an automatic control system.","The design applies two operating mechanisms, one of them operates the ball to rotate 90 degrees, and the other operates the said secondary valve body for driving the seat to sit against ball.","The design has many potential leakage paths, complicated structure and bulky size, and is not able to meet standard valve face-to-face dimensions.","Publication No.","CN103527809A, Application No.","2013105342621: Disclosed is a valve comprising a valve body, a valve bonnet , a valve stem, a wedged plug and sealing members, characterized in that the top of the valve body is connected with the valve bonnet, the valve stem is vertically mounted in the center of the top of the valve body through a support, the wedged plug in the cavity of the valve body is fixed at the bottom of the valve stem by a pin through a hole in the center of the valve bonnet to synchronize the movement of the valve stem and the wedged plug, that is, rotating and raising aligned to a fixed axis.","A fixed shaft is perpendicularly disposed in the bottom center of the cavity, the fixed shaft is matched with a hole in the bottom center of the wedged plug, the valve sealing members are fixed at the two sides of the bottom of the cavity through T-shaped grooves, valve sealing member stops are disposed on the top of the valve sealing member and on the inner walls of the two sides of the cavity, and the valve sealing member stops on the two sides are firmly connected with the two side walls of the wedged plug.","The design is actually a mechanical energized plug valve (also known as DBB plug valve in the industry), although the valve can achieve mechanical energized sealing in a closed position, owing to the sliding-type sealing member configuration, the valve sealing member to be influenced by the turbulence when the valve is in the open position.","At present, the design is used for applications under low pressure liquid working conditions only.","Publication No.","CN102979929A, Application No.","2012105315085: Disclosed is a valve comprising a ball, a seat and a sealing ring seat disposed between the ball and the seat to perform the sealing, and a hydraulic device for pushing the sealing ring seat in the axial direction of the sealing ring seat, the hydraulic device being disposed between the seat and the sealing ring seat.","The design realizes a forced seal by applying a pressure to the seal ring between the seat and the ball by using a set of hydraulic system, but the hydraulic leakage and complicated structure of the valve may affect the sealing reliability and service life of the valve.","Publication No.","CN105370909A, Application No.","2014104406033: Disclosed is an opening/closing part having two eccentric spherical members.","Such eccentric structure allows each of the two eccentric spherical surfaces to make a movement in the axial direction of the downstream seat and the upstream seat when the valve stem drives the opening/closing part to make a rotational movement, resulting in the effect of compressing or releasing the seat, thereby realizing the forced seal of the opening/closing part relative to the downstream seat and the upstream seat in a particular valve position.","The valve of the design may be influenced by turbulence in the opening position, the two eccentric spherical members may be damaged by turbulence vibration, which affects the reliability and service life of the valve.","Publication No.","CN104132157A, Application No.","2013101575904: Disclosed is a forced seal valve based on modular design and angular stroke operation, mainly comprising a valve body, an opening/closing part, a valve bonnet, a valve stem, a seat, a flow guide barrel, a seat support plate, a flow guide barrel support plate, an operating mechanism and a drainage valve.","The opening/closing part is arranged between the seat and the flow guide barrel, by adjusting the relative position of sphere center and radii of the convex spherical surface and center of the concave spherical surface, the thicknesses of individual portions of the opening/closing part can be adjusted to adjust the sealing specific pressure between the opening/closing part and the seat when the valve is located in different valve positions, so that the valve realizes a forced seal in a certain valve position.","Accordingly, the design is not a mechanical energized sealing ball valve in a whole sense.","SUMMARY An object of the invention is to provide a technical solution of mechanical energized sealing ball valve, thus improving the operating performance and sealing tightness of the ball valve.","In order to achieve the above purpose, the technical solution adopted by the invention is as follows: A mechanical energized sealing ball valve, comprising a seat, a ball assembly and a valve stem, characterized in that the ball assembly comprises a ball and a sealing member, the valve stem drives the ball to rotate between open position and close position, when the ball reaches the close position, the sealing member jacks-up of the ball to sit against the seat.","The ball is driven open and closed, and the sealing member sealed and unsealed, using a single valve stem.","This is in contrast to the prior art, where two or more valve stems were required for the separate operations of opening or closing the ball, and moving the sealing member toward or away from a seat.","Furthermore, a thread driving wheel is disposed on the ball and connected with the sealing member through threads, and the thread driving wheel jacks and retracts the sealing member through the threads during rotating.","Furthermore, the valve stem drives the thread driving wheel to rotate.","Furthermore, the thread driving wheel is cut with gear teeth, and the valve stem drives the thread driving wheel to rotate through a sealing driving gear.","Furthermore, an intermediate transmission gear is disposed between the thread driving wheel and the sealing driving gear.","These gears are alternatively referred to as a first, second, and third gear.","Furthermore, the sealing member and the ball are engaged by means of linear movement.","Furthermore, when the ball rotates to the close position from the open position, the ball stops rotating and the valve stem continues rotating towards the closing direction, so that the sealing member sits against the seat.","The sealing member is alternatively referred to as a sealing surface.","Furthermore, the rotation stroke of the ball is 90°.","Furthermore, the lower trunnion of the ball is provided with a 90° fan-shaped projection, and the lower trunnion chamber of the valve body is provided with a 180° limiting slot.","Furthermore, the valve stem drives the ball to rotate through an elastic component.","Furthermore, the elastic component is a torsion spring.","Furthermore, a torsion spring shaft is disposed at the bottom of the valve stem, with the torsion spring being sleeved on the torsion spring shaft, and the valve stem and the ball are respectively provided with torsion spring pin holes, with the torsion spring pins of the torsion spring being embedded into the torsion spring pin holes of the valve stem and the ball.","Furthermore, the elastic element applies to the ball a pre-driving force for rotating the ball towards the closing position.","Furthermore, the sealing member retracts towards the ball and contacts the ball during the opening process of the mechanical energized sealing ball valve.","The invention has the advantages that: the valve has a compact structure, the true sealing friction-free face in both open and close operation, the sealing force is even and reliable, the ball assembly is retracted and locked in the opening position to protect against turbulence-induced damage, the moment of ball valve operating torque is small, the open/close operation is rapid, and the valve stem seal is simple and reliable.","The invention will now be described in detail with reference to the accompanying drawings and examples.","BRIEF DESCRIPTION OF THE DRAWINGS FIG.","1 is a structural view of the invention, FIG.","2 is an exploded structural view of the invention, FIG.","3 is an exploded structural view of the invention, taken along the A axis of FIG.","2, FIG.","4 is a structural view of a ball, a seat, and a valve stem of the invention.","DETAILED DESCRIPTION As shown in FIG.","1-4, a mechanical energized sealing ball valve comprising a seat 10, a ball assembly and a valve stem 20, the ball assembly comprises a ball 30 and a sealing member 40, the valve stem drives the ball to make a rotation between open position and close position, when the ball rotates to the close position, the sealing member jacks out of the ball to sit against the seat.","A thread driving wheel 60 is disposed on the ball and connected with the sealing member through threads, and the thread driving wheel jacks up and get back the sealing member 40 through the threads during rotating.","Sealing member 40 is alternatively referred to as sealing surface 40.The valve stem 20 drives the thread driving wheel to rotate.","Note that only a single valve stem 20, or a first valve stem 20, is required for operation of both the ball 30 and sealing member 40.The thread driving wheel is cut with gear teeth 62, and the valve stem 20 drives the thread driving wheel to rotate through a sealing driving gear 70.An intermediate transmission gear 80 is disposed between the thread driving wheel and the sealing driving gear.","These gears are alternatively referred to as first, second, and third gears.","The sealing member and the ball is constrained by means of linear movement against ball.","The ball stops at close position while rotating to the close position from the open position, and the valve stem continues rotating towards the closing direction, drives the sealing member sit against the seat.","The rotation stroke of the ball is 90°.","The lower rotating shaft of the ball is provided with a 90° fan-shaped projection 33, and the lower rotating shaft chamber of the valve body is provided with a 180° limiting slot 13.The valve stem drives the ball to rotate through an elastic component 50.The elastic component is a torsion spring.","A torsion spring shaft 21 is disposed at the bottom end of the valve stem, with the torsion spring being sleeved on the torsion spring shaft, and the valve stem and the ball are respectively provided with torsion spring pin holes (22, 34), with the torsion spring pins of the torsion spring being embedded into the torsion spring pin holes of the valve stem and the ball.","The torsion spring applies to the ball a pre-driving force for rotating the ball towards the closing position.","The sealing member retracts towards the ball and contacts the ball during the opening of the valve.","Example 1 As shown in FIG.","1-4, a mechanical energized sealing ball valve comprises a seat 10, a ball assembly and a single valve stem 20, and the ball assembly comprises a ball 30 and a sealing member 40.The ball is mounted inside the valve body 11, the valve body is provided with an upper cover 14, and the valve stem is mounted within the upper cover.","The profile of the ball is spherical, the ball has a flow port 35 in a way that the axis of the ball flow port is perpendicular to the rotation axis of the ball (i.e., the rotation axis of the valve stem), and when the ball is located in the open position, the flow port is aligned to the seat, so that a medium flows through the ball valve.","The ball is provided with a jack-up guide hole 31, in this example, the jack-up guide hole being a hexagonal hole.","The axis X of the jack-up guide hole is perpendicular to the rotation axis Y of the ball and passes through the sphere center of the ball, and the axis of the jack-up guide hole is also perpendicular to the axis of the ball flow port.","A lower trunnion 32 is disposed at the lower end of the ball, the lower trunnion being coaxial to the rotation axis of the ball, and a 90° fan-shaped projection 33 is disposed at the end of the lower trunnion.","An upper trunnion 36 is disposed at the top of the ball, and a torsion spring pin hole 34 is disposed at the top of the upper trunnion.","An intermediate transmission shaft 37 is disposed between the upper trunnion and the jack-up guide hole.","The ball is provided with a ball-receiving surface 38 on the jack-up guide hole side, the ball-receiving surface being perpendicular to the axis of the jack-up guide hole.","The sealing member 40 is part of ball, comprising a spherical surface 43 and a ball-receiving matching face 44, and the sealing member is provided with a jack-up threaded hole 42 in the center of the ball-receiving matching face side.","The sealing member is constrained by means of linear movement against ball, a guide bar 41 is provided in the jack-up threaded hole, the guide bar is a hexagonal bar and in sliding fit with the jack-up guide hole 31 of the ball, so that the sealing member makes a reciprocating linear movement along the axis of the jack-up guide hole.","The hexagonal shaft disables the sealing member from rotating with respect to the ball, so that the thread driving wheel drives the sealing member through the threads in linear movement.","The thread driving wheel 60 is disposed on the ball, and the thread driving wheel is provided with a jack-up stud 61 which matches the jack-up threaded hole of the sealing member.","The thread driving wheel is cut gear teeth 62, which is coaxial to the jack-up stud, the teeth 62 are conical teeth.","The thread driving wheel is disposed on a shaft 39 of the ball through a locking ring 63.A sealing driving gear 70 is disposed on the valve stem, the sealing driving gear being a cone gear, and a polygonal hole 71 is disposed in the center of the sealing driving gear.","An intermediate transmission gear 80 is disposed between the thread driving wheel and the sealing driving gear such that the intermediate transmission gear is located on the intermediate transmission shaft 37 of the ball, the intermediate transmission gear being also a cone gear, and the intermediate transmission gear is engaged with the sealing driving gear and the gear teeth of the thread driving wheel respectively, so that the valve stem drives the thread driving wheel to rotate via the sealing driving gear, and the thread driving wheel drives the sealing member towards the seat back and forth via matched threads in between.","The ball is disposed within the valve body 11, the valve body is provided with a lower trunion chamber 12 corresponding to the lower trunion of the ball, the lower trunion chamber is provided with a 180-degree limiting slot 13 corresponding to the fan-shaped projection 33 at the bottom of the lower trunion of the ball.","Thus, the rotation stroke of the ball is limited to 90°.","The bottom of the valve stem is a polygon 23, and the top of sealing driving gear is in a driving mate with the bottom of the valve stem through the polygonal hole 71, so that the valve stem drives the sealing driving gear to rotate synchronously.","During the valve closing operation, the single valve stem drives the ball to rotate through a torsion spring 50.The connection end of the valve stem is provided with a torsion spring shaft 21 which extends into the valve stem, with the torsion spring being sleeved on the torsion spring shaft, the valve stem is provided with a torsion spring pin hole 22, and the two torsion spring pins of the torsion spring are embedded in the torsion spring pin hole 22 of the valve stem and the torsion spring pin hole 34 of the ball respectively.","It is desired that the torsion spring maintains a force on the ball, rotating the ball in the closing direction.","Thus, when the ball is in the open position, the torsion spring applies a pre-driving force to the ball, rotating the ball towards the closing direction.","With the driving mate between the valve stem and the sealing driving gear, the pre-driving force is transferred by the intermediate gear, so that thread driving gear drives the sealing member to tighten together against the ball, resulting in a balance.","The seat is provided with a seal 15 that matches with the spherical surface of the sealing member to build up sealing, and when the ball is in the opening position, a rotation gap is provided between the seat and the ball.","The valve stem drives the ball open and close.","During the valve closing operation, the valve stem drives the ball to rotate via the torsion spring 50.When the ball rotates from the open position towards the close position, due to the pre-driving force applied to the ball by the torsion spring, the ball rotates in synchronization with the valve stem, avoiding the relative rotation between the sealing driving gear and the ball, so that the sealing member does not jack up from the ball.","In the closed position, the ball stops rotating due to the fan-shaped projection 33 stop, while the valve stem keeps rotating towards the closing direction, so as to drive the sealing member to jack up the ball against the seat, resulting in the sealing contact between the spherical surface of the sealing member and the seal of the seat, thereby mechanical energized sealing is built.","In the opening process of the valve, the valve stem rotates towards the opening direction and drives the sealing driving gear to rotate synchronously.","Due to the force of the torsion spring, the ball does not rotate, and the sealing driving gear drives the sealing member to retract towards the ball, so that the ball-receiving matching face 44 of the sealing member is in contact with the ball-receiving surface 38 of the ball.","The valve stem keeps rotating towards the opening direction, and as the sealing member is in contact with the ball, the sealing driving gear stops rotating with respect to the ball, so that the valve stem drives the ball and the sealing member to reach the opening position simultaneously.","In order to ensure smooth open/close operation of the ball, after the sealing member retracts in place, the outer profile of the sealing member should not exceed the overall spherical profile of the ball, in this example, the outer profile of the sealing member and the outer profile of the ball form an integral spherical profile.","Example 2 In this example, a mechanical energized sealing ball valve is provided, which is a structural modification of the mechanical energized sealing ball valve of Example 1.According to the mechanical energized sealing ball valve of this example, two sealing members are disposed on the ball and both mate with an upstream seat and a downstream seat.","Example 3 In this example, a mechanical energized sealing ball valve is provided, which is a structural modification of the mechanical energized sealing ball valve of Example 1.A thread-driving wheel is disposed on a ball and connected with a sealing member through threads, and the thread driving wheel drives the sealing member to jack up the ball during rotating.","The thread driving wheel is provided with a threaded hole, the sealing member is provided with a stud which matches threaded hole of the thread driving wheel.","The thread driving wheel drives the sealing member to jack up and get back towards a seat through the threaded hole.","Example 4 In this example, a mechanical energized sealing ball valve is provided, which is a structural modification of the mechanical energized sealing ball valve of Example 1.The sealing member is provided with a guide hole, the guide hole being a prismatic hole, the ball is provided with a guide shaft, the guide shaft being a prismatic shaft in sliding fit with the prismatic hole of the sealing member.","Example 5 In this example, a mechanical energized sealing ball valve is provided, which is a structural modification of the mechanical energized sealing ball valve of Example 4.In this example, the ball and the sealing member are connected through a key shaft match, so that the sealing member jack up and get back towards the seat.","Example 6 In this example, a mechanical energized sealing ball valve is provided, which is a structural modification of the mechanical energized sealing ball valve of Example 1 or Example 4.In this example, the ball and the sealing member are connected through a splined shaft match, so that the sealing member jack up and get back towards the seat.","Example 7 In this example, a mechanical energized sealing ball valve is provided, which is a structural modification of the mechanical energized sealing ball valve of Example 1.The bottom of the valve stem is a spline, and the sealing driving gear top is provided with a splined hole which is engaged with the connection end of the valve stem.","The sealing driving gear forms a driving mate with the bottom of the valve stem through the splined hole, so that the valve stem drives the sealing driving gear to rotate synchronously.","Example 8 In this example, a mechanical energized sealing ball valve is provided, which is a structural modification of the mechanical energized sealing ball valve of Example 1.In this example, the valve body is side-entry body configuration.","Example 9 In this example, a mechanical energized sealing ball valve is provided, which is a structural modification of the mechanical energized sealing ball valve of Example 1.In this example, the valve body is all-welded body configuration.","Based on the basic principle of sealing, the invention fully solves the issues and concerns of the existing mechanical energized sealing ball valves.","For example, the following issues and concerns are solved: relative sliding friction at the final stage of siting movement, insufficient normal component of sealing force of the seat, large structure and bulky size, need of hydraulic systems in certain designs, and potential damages caused by turbulence on the ball/plug assembly in case that the valve is in the open position in certain design.","The invention adopts the design of trunnion mounted ball and stationary seat.","A part of the ball assembly (for a plug valve, a part of the plug assembly), i.e., sealing member, is jacked towards the seat by the threaded jack-up mechanism, thereby build up sealing by mechanical energized force.","The range of movement of the ball of the valve is limited by fine stop at the lower trunnion chamber of the valve body, thereby accurately stopped in 90-degree open/close position; with the torsion spring, the sealing member is tightened and locked against the ball in all other positions than the sealing position, so that 90 degree ball-seat friction free rotation can be achieved.","In addition, the concern in the existing designs that sealing member and/or other parts attached to ball are damaged by turbulence is solved.","After being aligned to the closing position, the ball stops rotating by fine stop of the lower trunnion, at this moment, the thread driving wheel is rotated by valve close torque transmitted by a set of gear mechanisms integrated to the ball, so that the sealing member is jacked up against seat firmly, and mechanical energized torque sealing is built.","Such seating movement is evenly and aligning the normal vertical direction of the seat, so that there is no relative rotating/sliding friction between the sealing surfaces, thereby avoiding the relative sliding friction between the sealing surfaces at the final stage of the closing stroke of the conventional mechanical energized ball valves.","With the principle of thread jack up configuration, the sealing member acts steadily and reliably, thereby ensuring the accuracy of siting between the sealing member and seat sealing surfaces.","The valve has a compact structure which can conform to the standard face-to-face dimension, even may be shorter.","The valve stem seal is a typical rotation stem seal configuration, which is uncomplicated and reliable.","Only a single valve stem is needed to perform both the ball rotation, and sealing/unsealing, operations.","Also, the time of valve open/close stroke is short.","The invention has the innovation in the following aspects: Smoothly-operating sealing member thread jack-up mechanism; Aligning the same axial, the seat is positioned after the sealing member, after the thread driving wheel, after the ball.","While closing the valve, thread driving wheel can only be energized by the operating torque and to rotate when the ball and the sealing member align to the seat, given the fact that the sealing member is guided by its hexagonal shaft, the sealing member is jacked up by thread driving wheel rather than being rotated together with the thread driving wheel, and sited against seat eventually, and mechanical energized sealing is built thereby.","In this process, the thread jack-up action produces a sitting force perpendicular to the seat sealing surface, which avoids sliding friction as there is no any kind of rotation movement other than the jack-up press, sealing build-up is reliable and evenly.","Again, the operations of changing the open and closed position, as well as sealed and unsealed position, require only a single valve stem.","Feature of self-cleaning: While opening valve as the seat and the sealing member move apart evenly: on top of torsion spring force, valve open torque will drive valve open.","It starts from the reverse rotation of the thread driving wheel, and due to the guide of the hexagonal shaft, the sealing member is disengaged from the seat rather than rotating together with the thread driving wheel, and finally locked tightly against the ball under the torsion spring force and the valve-opening torque, at this moment, the ball assembly will rotate until the valve is fully opened.","In this process, the sealing member and the seat move apart evenly without any rotation movement in between the sealing member and the sea, and if foreign things are accumulated around the seat, the foreign things may be uniformly swept off by the medium at any angle, thereby it can be self-cleaned.","The torque for opening/closing the valve is directly applied to the sealing driving gear through the valve stem.","Before the sealing member and the seat are aligned, the gear set remains locked without rotation, and when the sealing member and the seat are aligned, the valve stem rotating torque firstly drives the sealing driving gear to rotate, then the torque is transferred to the thread driving wheel by the intermediate transmission gear, so that the thread driving wheel rotates the thread jack-up mechanism directly, thereby achieve mechanical energized sealing.","By using the intermediate transmission gear for torque transferring, the size of the ball assembly can be greatly reduced, and thus greatly reduce the size of the whole valve.","The torsion spring locking device functions interlink movement of the ball and the sealing driving gear: the torsion spring having a simple and reliable structure is disposed between the valve stem and the ball, The polygonal shaft at bottom of the valve stem is engaged with the polygonal hole at the top sealing driving gear to form the driving mate (alternatively, splined mate), once the sealing member and the ball are tightened by the gear set mechanism, an appropriate locking torque is applied to them by the torsion spring between the ball and valve stem, so that the sealing member and the ball are locked during the valve opening/closing stroke without contacting against the seat, to achieve friction-free ball rotation.","While closing the valve, the sealing member and the seat are aligned, the rotation of the ball is stopped, valve-closing torque transferred through valve stem continuously will overcome the torsion spring force, so that the sealing driving gear rotates with respect to the ball to transfer the torque to the sealing member through the gear set mechanism to build up mechanical energized sealing.","While opening the valve, the torsion spring will apply a torsion force to maintain the ball in the closing position, valve opening torque will drive the gear set mechanism and further drive sealing member to be tightened against the ball firstly, also the torsion spring will apply force on top to the valve closing torque to lock tightly the sealing member to the ball.","The valve stem keeps rotating towards the valve opening direction, and the ball assembly rotates together with the valve stem until reaching the valve full-opening position.","The torsion spring forms a simple-structure interlinked the movement of the valve stem, the ball and sealing driving gear, enables the ball assembly been tightened and locked in other positions than the full-closing position, as a result, the friction-free 90-degree rotation of the ball assembly is achieved, on the other hand, the potential damage of sealing member caused by the vibration due to turbulence of medium can be avoided when the valve is in full-open position.","The mechanical stop at valve lower trunnion separates the joint movement of the ball and the sealing driving gear: Different from the conventional trunnion mounted ball valve, the lower trunnion of the ball is provided with a 90° fan-shaped projection, and the lower trunnion chamber of the valve body is provided with the 180° limiting slot corresponding to the lower trunnion of the ball.","After the valve is assembled, the movement of the ball is strictly limited within the range of 90-degree open/close.","When the ball is stopped at a closed position, valve closing torque applied by stem will overcome the force of torsion spring and drive gear set mechanism and rotate the threaded jack-up mechanism to achieve mechanical energized sealing."]],"string":"[\n [\n \"Mechanical energized sealing ball valve\",\n \"The invention relates to a mechanical energized sealing ball valve comprising a seat, a ball assembly, and a single valve stem that operates both the sealing member and the ball.\",\n \"The ball comprises a ball and a sealing member.\",\n \"The valve stem drives the ball to rotate between open position and close position.\",\n \"When the ball reaches the close position, the sealing member, operated by the same valve stem, moves away from the ball to press and sit against the seat.\",\n \"The invention has the advantages that: the valve has a compact structure, the friction-free on/off is achieved, the mechanical energized sealing force is even and reliable, the ball is retracted and locked in the opening position to protect against turbulence-induced damage, low operating torque, the open/close operation is rapid, and the valve stem seal operates simply and reliably.\"\n ],\n [\n \"1.A ball valve with single-action actuation and sealing, the ball valve comprising: a ball assembly, the ball assembly including a ball and a sealing member, the ball assembly having an open position and a closed position; a first valve stem, the first valve stem causing both rotation of the ball and motion of the sealing member; a valve seat; wherein when the ball assembly is in the open position, rotation of the first valve stem first rotates the ball to the closed position, and then causes the sealing member to move linearly towards the valve seat causing the sealing member to press against the valve seat.\",\n \"2.The ball valve of claim 1, wherein the first valve stem is mechanically coupled to the sealing member using a first gear, a second gear, and a third gear.\",\n \"3.The ball valve of claim 1, wherein the first gear is coaxial with the first valve stem, and the third gear is coaxial with the sealing member.\",\n \"4.The ball valve of claim 1, wherein the first valve stem is mechanically coupled to the ball by means of a spring.\",\n \"5.The ball valve of claim 1, wherein a lower trunnion of the ball is provided with a 90° fan-shaped projection, and a lower trunnion chamber of a valve body is provided with a 180° limiting slot.\",\n \"6.A ball valve with sequential ball actuation and seal actuation using a single valve stem, the ball valve comprising: a ball, the ball having an open position and a closed position, the ball actuated by the single valve stem during a closure operation; a sealing surface, the sealing surface moving inward and outward with respect to the ball, the sealing surface actuated by the single valve stem during a sealing operation; the sealing surface pressing against a seat when in a sealed position; the closure operation and sealing operation being automatically sequenced depending upon the position of the ball; wherein when the ball is in an open position, rotation of the single valve stem causes the closure operation to occur, and upon the ball reaching a closed position, the single valve stem then causes the sealing operation to occur; wherein when the ball is in a closed position, rotation of the single valve stem causes the sealing operation to occur, and upon the ball reaching an open position, the single valve stem then causes the closure operation to occur.\",\n \"7.The ball valve of claim 6, wherein the single valve stem is mechanically coupled to the sealing surface using a first gear, a second gear, and a third gear.\",\n \"8.The ball valve of claim 7, wherein the first gear is coaxial with the single valve stem, the third gear is coaxial with the sealing surface.\",\n \"9.The ball valve of claim 6, wherein the single valve stem is mechanically coupled to the ball by means of a spring.\",\n \"10.The ball valve of claim 6, wherein a lower trunnion of the ball is provided with a 90° fan-shaped projection, and a lower trunnion chamber of a valve body is provided with a 180° limiting slot.\",\n \"11.A mechanical energized sealing ball valve, comprising: a seat; a ball assembly; and a single valve stem, the single valve stem independent of any other valve stem; wherein the ball assembly comprises a ball and a sealing member; the single valve stem rotating the ball and operating the sealing member; wherein rotation of the single valve stem first causes the ball to rotate between an open position and a closed position, and when the ball reaches the closed position, the continued rotation of the valve stem presses the sealing member against the seat.\",\n \"12.The mechanical energized sealing ball valve according to claim 11, wherein a thread driving wheel is disposed on the ball and connected with the sealing member through threads, and the thread driving wheel causes the sealing member to move inwardly and outwardly.\",\n \"13.The mechanical energized sealing ball valve according to claim 12, wherein the valve stem causes the thread driving wheel to rotate.\",\n \"14.The mechanical energized sealing ball valve according to claim 12, wherein the thread driving wheel is cut with gear teeth, and the single valve stem causes the thread driving wheel to rotate by way of a sealing driving gear.\",\n \"15.The mechanical energized sealing ball valve according to claim 14, wherein an intermediate transmission gear is disposed between the thread driving wheel and the sealing driving gear.\",\n \"16.The mechanical energized sealing ball valve according to claim 11 wherein when the ball rotates to the closed position from the open position, the ball stops rotating and the single valve stem continues rotating towards the closing direction, causing the sealing member to sit against the seat.\",\n \"17.The mechanical energized sealing ball valve according to claim 11, wherein a lower trunnion of the ball is provided with a 90° fan-shaped projection, and a lower trunnion chamber of a valve body is provided with a 180° limiting slot.\",\n \"18.The mechanical energized sealing ball valve according to claim 11, wherein the single valve stem drives the ball to rotate using an elastic component.\",\n \"19.The mechanical energized sealing ball valve according to claim 18, wherein the elastic component is a torsion spring.\",\n \"20.The mechanical energized sealing ball valve according to claim 18, wherein the elastic element applies a pre-driving force to the ball for rotating the ball towards the closing position.\"\n ],\n [\n \" BACKGROUND In the flow control application, for example, oil/gas production process switching, pipeline shut-off, metering, pressure regulation, molecular sieve switching, compressor inlet/outlet, hydrogen application in oil refining process, air separation of synthetic ammonia equipment, and the like, which require frequent operation and have strict requirements on flow on-off control and closing tightness, it is desired that valves produce a pressure drop as small as possible and can provide a forced torque seal without the influence of the pressure of fluid within the pipeline.\",\n \"Mechanical energized sealing ball valves are recognized as an ideal solution.\",\n \"However, for the conventional rising stem mechanical energized sealing ball valve, although there is no contact or friction between the ball and the seat during most of the opening/closing stroke, sliding friction exists between the ball and seat sealing area during the final ball-seat engagement stage.\",\n \"Thus, valve operation is not a true friction-free rotation, and the ball against seat sealing relies on the stem wedging against ball, with ball being held by lower trunnion.\",\n \"As a result the movement is unsteady and susceptible to the influence of tolerance of the relative position of the seat and the lower trunnion.\",\n \"Additionally, the valve stem portion and its assembly have a complicated structure and require the combination of linear movement and rotation movement during the opening/closing process.\",\n \"The requirement for machining precision is strict, the risk of valve stem leakage is high, and the time of opening/closing operation is too long.\",\n \"The following six documents of mechanical energized sealing ball valve are found by SIPO patent inquiry: Publication No.\",\n \"CN104295764A, Application No.\",\n \"2014105008955: Disclosed is a valve that opens or close using a valve stem and a ball in eccentric arrangement and synchronous rotation.\",\n \"The design is essentially a modification of eccentric butterfly valve, in which a relative sliding friction between seat and ball sealing surface is produced due to a large angular stroke vector existing during the final siting stage of the ball and seat.\",\n \"Thus, it is not a true friction-free rotation, as the closing operation is an angular stroke, and the resulting normal component of force between the ball and the seat is not large, which may impact the sealing reliability and actual service life.\",\n \"Publication No.\",\n \"CN103727260A, Application No.\",\n \"2014100163761: Disclosed is a ball valve, in particular a mechanical energized sealing ball valve, comprising a valve body, a secondary valve body, a ball, a seat, and a secondary valve body fluid port, and a stud-nut-driving-type mechanical energized sealing device disposed on the shell of the secondary valve body fluid port.\",\n \"The worm wheel and the driving stud are coupled via a flat key, when the driving stud makes a rotational movement, the axial sliding key groove of the driven nut fits the driving stud in a rotating manner, enabling an axial linear movement along the guide key on the secondary valve body fluid port.\",\n \"As a result, a desired sealing specific pressure is generated between the seat and the ball within the valve cavity by the pressure generated outside the body through a pressure transfer system, thereby low-torque opening/closing and mechanical energized sealing can be achieved, and the interlinked actuation of the stud-nut energized sealing device and the electric actuator during opening/closing and sealing process are completed through an automatic control system.\",\n \"The design applies two operating mechanisms, one of them operates the ball to rotate 90 degrees, and the other operates the said secondary valve body for driving the seat to sit against ball.\",\n \"The design has many potential leakage paths, complicated structure and bulky size, and is not able to meet standard valve face-to-face dimensions.\",\n \"Publication No.\",\n \"CN103527809A, Application No.\",\n \"2013105342621: Disclosed is a valve comprising a valve body, a valve bonnet , a valve stem, a wedged plug and sealing members, characterized in that the top of the valve body is connected with the valve bonnet, the valve stem is vertically mounted in the center of the top of the valve body through a support, the wedged plug in the cavity of the valve body is fixed at the bottom of the valve stem by a pin through a hole in the center of the valve bonnet to synchronize the movement of the valve stem and the wedged plug, that is, rotating and raising aligned to a fixed axis.\",\n \"A fixed shaft is perpendicularly disposed in the bottom center of the cavity, the fixed shaft is matched with a hole in the bottom center of the wedged plug, the valve sealing members are fixed at the two sides of the bottom of the cavity through T-shaped grooves, valve sealing member stops are disposed on the top of the valve sealing member and on the inner walls of the two sides of the cavity, and the valve sealing member stops on the two sides are firmly connected with the two side walls of the wedged plug.\",\n \"The design is actually a mechanical energized plug valve (also known as DBB plug valve in the industry), although the valve can achieve mechanical energized sealing in a closed position, owing to the sliding-type sealing member configuration, the valve sealing member to be influenced by the turbulence when the valve is in the open position.\",\n \"At present, the design is used for applications under low pressure liquid working conditions only.\",\n \"Publication No.\",\n \"CN102979929A, Application No.\",\n \"2012105315085: Disclosed is a valve comprising a ball, a seat and a sealing ring seat disposed between the ball and the seat to perform the sealing, and a hydraulic device for pushing the sealing ring seat in the axial direction of the sealing ring seat, the hydraulic device being disposed between the seat and the sealing ring seat.\",\n \"The design realizes a forced seal by applying a pressure to the seal ring between the seat and the ball by using a set of hydraulic system, but the hydraulic leakage and complicated structure of the valve may affect the sealing reliability and service life of the valve.\",\n \"Publication No.\",\n \"CN105370909A, Application No.\",\n \"2014104406033: Disclosed is an opening/closing part having two eccentric spherical members.\",\n \"Such eccentric structure allows each of the two eccentric spherical surfaces to make a movement in the axial direction of the downstream seat and the upstream seat when the valve stem drives the opening/closing part to make a rotational movement, resulting in the effect of compressing or releasing the seat, thereby realizing the forced seal of the opening/closing part relative to the downstream seat and the upstream seat in a particular valve position.\",\n \"The valve of the design may be influenced by turbulence in the opening position, the two eccentric spherical members may be damaged by turbulence vibration, which affects the reliability and service life of the valve.\",\n \"Publication No.\",\n \"CN104132157A, Application No.\",\n \"2013101575904: Disclosed is a forced seal valve based on modular design and angular stroke operation, mainly comprising a valve body, an opening/closing part, a valve bonnet, a valve stem, a seat, a flow guide barrel, a seat support plate, a flow guide barrel support plate, an operating mechanism and a drainage valve.\",\n \"The opening/closing part is arranged between the seat and the flow guide barrel, by adjusting the relative position of sphere center and radii of the convex spherical surface and center of the concave spherical surface, the thicknesses of individual portions of the opening/closing part can be adjusted to adjust the sealing specific pressure between the opening/closing part and the seat when the valve is located in different valve positions, so that the valve realizes a forced seal in a certain valve position.\",\n \"Accordingly, the design is not a mechanical energized sealing ball valve in a whole sense.\"\n ],\n [\n \" SUMMARY An object of the invention is to provide a technical solution of mechanical energized sealing ball valve, thus improving the operating performance and sealing tightness of the ball valve.\",\n \"In order to achieve the above purpose, the technical solution adopted by the invention is as follows: A mechanical energized sealing ball valve, comprising a seat, a ball assembly and a valve stem, characterized in that the ball assembly comprises a ball and a sealing member, the valve stem drives the ball to rotate between open position and close position, when the ball reaches the close position, the sealing member jacks-up of the ball to sit against the seat.\",\n \"The ball is driven open and closed, and the sealing member sealed and unsealed, using a single valve stem.\",\n \"This is in contrast to the prior art, where two or more valve stems were required for the separate operations of opening or closing the ball, and moving the sealing member toward or away from a seat.\",\n \"Furthermore, a thread driving wheel is disposed on the ball and connected with the sealing member through threads, and the thread driving wheel jacks and retracts the sealing member through the threads during rotating.\",\n \"Furthermore, the valve stem drives the thread driving wheel to rotate.\",\n \"Furthermore, the thread driving wheel is cut with gear teeth, and the valve stem drives the thread driving wheel to rotate through a sealing driving gear.\",\n \"Furthermore, an intermediate transmission gear is disposed between the thread driving wheel and the sealing driving gear.\",\n \"These gears are alternatively referred to as a first, second, and third gear.\",\n \"Furthermore, the sealing member and the ball are engaged by means of linear movement.\",\n \"Furthermore, when the ball rotates to the close position from the open position, the ball stops rotating and the valve stem continues rotating towards the closing direction, so that the sealing member sits against the seat.\",\n \"The sealing member is alternatively referred to as a sealing surface.\",\n \"Furthermore, the rotation stroke of the ball is 90°.\",\n \"Furthermore, the lower trunnion of the ball is provided with a 90° fan-shaped projection, and the lower trunnion chamber of the valve body is provided with a 180° limiting slot.\",\n \"Furthermore, the valve stem drives the ball to rotate through an elastic component.\",\n \"Furthermore, the elastic component is a torsion spring.\",\n \"Furthermore, a torsion spring shaft is disposed at the bottom of the valve stem, with the torsion spring being sleeved on the torsion spring shaft, and the valve stem and the ball are respectively provided with torsion spring pin holes, with the torsion spring pins of the torsion spring being embedded into the torsion spring pin holes of the valve stem and the ball.\",\n \"Furthermore, the elastic element applies to the ball a pre-driving force for rotating the ball towards the closing position.\",\n \"Furthermore, the sealing member retracts towards the ball and contacts the ball during the opening process of the mechanical energized sealing ball valve.\",\n \"The invention has the advantages that: the valve has a compact structure, the true sealing friction-free face in both open and close operation, the sealing force is even and reliable, the ball assembly is retracted and locked in the opening position to protect against turbulence-induced damage, the moment of ball valve operating torque is small, the open/close operation is rapid, and the valve stem seal is simple and reliable.\",\n \"The invention will now be described in detail with reference to the accompanying drawings and examples.\"\n ],\n [\n \"CROSS-REFERENCE TO RELATED APPLICATION This application is a continuation of U.S. patent application Ser.\",\n \"No.\",\n \"15/678,507, filed Aug. 16, 2017, titled “A mechanical energized sealing ball valve”, which is in turn a continuation of PCT application number PCT/CN2017/080179, filed Apr.\",\n \"12, 2017, title translated as “Forced Sealing Ball Valve,” which in turn claims priority to China application number ZL 2016 20491127.2, filed May 26, 2016, title translated as “Forced Sealing Ball Valve.” FIELD The invention is a ball valve, and in particular a mechanical energized sealing ball valve.\",\n \"BACKGROUND In the flow control application, for example, oil/gas production process switching, pipeline shut-off, metering, pressure regulation, molecular sieve switching, compressor inlet/outlet, hydrogen application in oil refining process, air separation of synthetic ammonia equipment, and the like, which require frequent operation and have strict requirements on flow on-off control and closing tightness, it is desired that valves produce a pressure drop as small as possible and can provide a forced torque seal without the influence of the pressure of fluid within the pipeline.\",\n \"Mechanical energized sealing ball valves are recognized as an ideal solution.\",\n \"However, for the conventional rising stem mechanical energized sealing ball valve, although there is no contact or friction between the ball and the seat during most of the opening/closing stroke, sliding friction exists between the ball and seat sealing area during the final ball-seat engagement stage.\",\n \"Thus, valve operation is not a true friction-free rotation, and the ball against seat sealing relies on the stem wedging against ball, with ball being held by lower trunnion.\",\n \"As a result the movement is unsteady and susceptible to the influence of tolerance of the relative position of the seat and the lower trunnion.\",\n \"Additionally, the valve stem portion and its assembly have a complicated structure and require the combination of linear movement and rotation movement during the opening/closing process.\",\n \"The requirement for machining precision is strict, the risk of valve stem leakage is high, and the time of opening/closing operation is too long.\",\n \"The following six documents of mechanical energized sealing ball valve are found by SIPO patent inquiry: Publication No.\",\n \"CN104295764A, Application No.\",\n \"2014105008955: Disclosed is a valve that opens or close using a valve stem and a ball in eccentric arrangement and synchronous rotation.\",\n \"The design is essentially a modification of eccentric butterfly valve, in which a relative sliding friction between seat and ball sealing surface is produced due to a large angular stroke vector existing during the final siting stage of the ball and seat.\",\n \"Thus, it is not a true friction-free rotation, as the closing operation is an angular stroke, and the resulting normal component of force between the ball and the seat is not large, which may impact the sealing reliability and actual service life.\",\n \"Publication No.\",\n \"CN103727260A, Application No.\",\n \"2014100163761: Disclosed is a ball valve, in particular a mechanical energized sealing ball valve, comprising a valve body, a secondary valve body, a ball, a seat, and a secondary valve body fluid port, and a stud-nut-driving-type mechanical energized sealing device disposed on the shell of the secondary valve body fluid port.\",\n \"The worm wheel and the driving stud are coupled via a flat key, when the driving stud makes a rotational movement, the axial sliding key groove of the driven nut fits the driving stud in a rotating manner, enabling an axial linear movement along the guide key on the secondary valve body fluid port.\",\n \"As a result, a desired sealing specific pressure is generated between the seat and the ball within the valve cavity by the pressure generated outside the body through a pressure transfer system, thereby low-torque opening/closing and mechanical energized sealing can be achieved, and the interlinked actuation of the stud-nut energized sealing device and the electric actuator during opening/closing and sealing process are completed through an automatic control system.\",\n \"The design applies two operating mechanisms, one of them operates the ball to rotate 90 degrees, and the other operates the said secondary valve body for driving the seat to sit against ball.\",\n \"The design has many potential leakage paths, complicated structure and bulky size, and is not able to meet standard valve face-to-face dimensions.\",\n \"Publication No.\",\n \"CN103527809A, Application No.\",\n \"2013105342621: Disclosed is a valve comprising a valve body, a valve bonnet , a valve stem, a wedged plug and sealing members, characterized in that the top of the valve body is connected with the valve bonnet, the valve stem is vertically mounted in the center of the top of the valve body through a support, the wedged plug in the cavity of the valve body is fixed at the bottom of the valve stem by a pin through a hole in the center of the valve bonnet to synchronize the movement of the valve stem and the wedged plug, that is, rotating and raising aligned to a fixed axis.\",\n \"A fixed shaft is perpendicularly disposed in the bottom center of the cavity, the fixed shaft is matched with a hole in the bottom center of the wedged plug, the valve sealing members are fixed at the two sides of the bottom of the cavity through T-shaped grooves, valve sealing member stops are disposed on the top of the valve sealing member and on the inner walls of the two sides of the cavity, and the valve sealing member stops on the two sides are firmly connected with the two side walls of the wedged plug.\",\n \"The design is actually a mechanical energized plug valve (also known as DBB plug valve in the industry), although the valve can achieve mechanical energized sealing in a closed position, owing to the sliding-type sealing member configuration, the valve sealing member to be influenced by the turbulence when the valve is in the open position.\",\n \"At present, the design is used for applications under low pressure liquid working conditions only.\",\n \"Publication No.\",\n \"CN102979929A, Application No.\",\n \"2012105315085: Disclosed is a valve comprising a ball, a seat and a sealing ring seat disposed between the ball and the seat to perform the sealing, and a hydraulic device for pushing the sealing ring seat in the axial direction of the sealing ring seat, the hydraulic device being disposed between the seat and the sealing ring seat.\",\n \"The design realizes a forced seal by applying a pressure to the seal ring between the seat and the ball by using a set of hydraulic system, but the hydraulic leakage and complicated structure of the valve may affect the sealing reliability and service life of the valve.\",\n \"Publication No.\",\n \"CN105370909A, Application No.\",\n \"2014104406033: Disclosed is an opening/closing part having two eccentric spherical members.\",\n \"Such eccentric structure allows each of the two eccentric spherical surfaces to make a movement in the axial direction of the downstream seat and the upstream seat when the valve stem drives the opening/closing part to make a rotational movement, resulting in the effect of compressing or releasing the seat, thereby realizing the forced seal of the opening/closing part relative to the downstream seat and the upstream seat in a particular valve position.\",\n \"The valve of the design may be influenced by turbulence in the opening position, the two eccentric spherical members may be damaged by turbulence vibration, which affects the reliability and service life of the valve.\",\n \"Publication No.\",\n \"CN104132157A, Application No.\",\n \"2013101575904: Disclosed is a forced seal valve based on modular design and angular stroke operation, mainly comprising a valve body, an opening/closing part, a valve bonnet, a valve stem, a seat, a flow guide barrel, a seat support plate, a flow guide barrel support plate, an operating mechanism and a drainage valve.\",\n \"The opening/closing part is arranged between the seat and the flow guide barrel, by adjusting the relative position of sphere center and radii of the convex spherical surface and center of the concave spherical surface, the thicknesses of individual portions of the opening/closing part can be adjusted to adjust the sealing specific pressure between the opening/closing part and the seat when the valve is located in different valve positions, so that the valve realizes a forced seal in a certain valve position.\",\n \"Accordingly, the design is not a mechanical energized sealing ball valve in a whole sense.\",\n \"SUMMARY An object of the invention is to provide a technical solution of mechanical energized sealing ball valve, thus improving the operating performance and sealing tightness of the ball valve.\",\n \"In order to achieve the above purpose, the technical solution adopted by the invention is as follows: A mechanical energized sealing ball valve, comprising a seat, a ball assembly and a valve stem, characterized in that the ball assembly comprises a ball and a sealing member, the valve stem drives the ball to rotate between open position and close position, when the ball reaches the close position, the sealing member jacks-up of the ball to sit against the seat.\",\n \"The ball is driven open and closed, and the sealing member sealed and unsealed, using a single valve stem.\",\n \"This is in contrast to the prior art, where two or more valve stems were required for the separate operations of opening or closing the ball, and moving the sealing member toward or away from a seat.\",\n \"Furthermore, a thread driving wheel is disposed on the ball and connected with the sealing member through threads, and the thread driving wheel jacks and retracts the sealing member through the threads during rotating.\",\n \"Furthermore, the valve stem drives the thread driving wheel to rotate.\",\n \"Furthermore, the thread driving wheel is cut with gear teeth, and the valve stem drives the thread driving wheel to rotate through a sealing driving gear.\",\n \"Furthermore, an intermediate transmission gear is disposed between the thread driving wheel and the sealing driving gear.\",\n \"These gears are alternatively referred to as a first, second, and third gear.\",\n \"Furthermore, the sealing member and the ball are engaged by means of linear movement.\",\n \"Furthermore, when the ball rotates to the close position from the open position, the ball stops rotating and the valve stem continues rotating towards the closing direction, so that the sealing member sits against the seat.\",\n \"The sealing member is alternatively referred to as a sealing surface.\",\n \"Furthermore, the rotation stroke of the ball is 90°.\",\n \"Furthermore, the lower trunnion of the ball is provided with a 90° fan-shaped projection, and the lower trunnion chamber of the valve body is provided with a 180° limiting slot.\",\n \"Furthermore, the valve stem drives the ball to rotate through an elastic component.\",\n \"Furthermore, the elastic component is a torsion spring.\",\n \"Furthermore, a torsion spring shaft is disposed at the bottom of the valve stem, with the torsion spring being sleeved on the torsion spring shaft, and the valve stem and the ball are respectively provided with torsion spring pin holes, with the torsion spring pins of the torsion spring being embedded into the torsion spring pin holes of the valve stem and the ball.\",\n \"Furthermore, the elastic element applies to the ball a pre-driving force for rotating the ball towards the closing position.\",\n \"Furthermore, the sealing member retracts towards the ball and contacts the ball during the opening process of the mechanical energized sealing ball valve.\",\n \"The invention has the advantages that: the valve has a compact structure, the true sealing friction-free face in both open and close operation, the sealing force is even and reliable, the ball assembly is retracted and locked in the opening position to protect against turbulence-induced damage, the moment of ball valve operating torque is small, the open/close operation is rapid, and the valve stem seal is simple and reliable.\",\n \"The invention will now be described in detail with reference to the accompanying drawings and examples.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS FIG.\",\n \"1 is a structural view of the invention, FIG.\",\n \"2 is an exploded structural view of the invention, FIG.\",\n \"3 is an exploded structural view of the invention, taken along the A axis of FIG.\",\n \"2, FIG.\",\n \"4 is a structural view of a ball, a seat, and a valve stem of the invention.\",\n \"DETAILED DESCRIPTION As shown in FIG.\",\n \"1-4, a mechanical energized sealing ball valve comprising a seat 10, a ball assembly and a valve stem 20, the ball assembly comprises a ball 30 and a sealing member 40, the valve stem drives the ball to make a rotation between open position and close position, when the ball rotates to the close position, the sealing member jacks out of the ball to sit against the seat.\",\n \"A thread driving wheel 60 is disposed on the ball and connected with the sealing member through threads, and the thread driving wheel jacks up and get back the sealing member 40 through the threads during rotating.\",\n \"Sealing member 40 is alternatively referred to as sealing surface 40.The valve stem 20 drives the thread driving wheel to rotate.\",\n \"Note that only a single valve stem 20, or a first valve stem 20, is required for operation of both the ball 30 and sealing member 40.The thread driving wheel is cut with gear teeth 62, and the valve stem 20 drives the thread driving wheel to rotate through a sealing driving gear 70.An intermediate transmission gear 80 is disposed between the thread driving wheel and the sealing driving gear.\",\n \"These gears are alternatively referred to as first, second, and third gears.\",\n \"The sealing member and the ball is constrained by means of linear movement against ball.\",\n \"The ball stops at close position while rotating to the close position from the open position, and the valve stem continues rotating towards the closing direction, drives the sealing member sit against the seat.\",\n \"The rotation stroke of the ball is 90°.\",\n \"The lower rotating shaft of the ball is provided with a 90° fan-shaped projection 33, and the lower rotating shaft chamber of the valve body is provided with a 180° limiting slot 13.The valve stem drives the ball to rotate through an elastic component 50.The elastic component is a torsion spring.\",\n \"A torsion spring shaft 21 is disposed at the bottom end of the valve stem, with the torsion spring being sleeved on the torsion spring shaft, and the valve stem and the ball are respectively provided with torsion spring pin holes (22, 34), with the torsion spring pins of the torsion spring being embedded into the torsion spring pin holes of the valve stem and the ball.\",\n \"The torsion spring applies to the ball a pre-driving force for rotating the ball towards the closing position.\",\n \"The sealing member retracts towards the ball and contacts the ball during the opening of the valve.\",\n \"Example 1 As shown in FIG.\",\n \"1-4, a mechanical energized sealing ball valve comprises a seat 10, a ball assembly and a single valve stem 20, and the ball assembly comprises a ball 30 and a sealing member 40.The ball is mounted inside the valve body 11, the valve body is provided with an upper cover 14, and the valve stem is mounted within the upper cover.\",\n \"The profile of the ball is spherical, the ball has a flow port 35 in a way that the axis of the ball flow port is perpendicular to the rotation axis of the ball (i.e., the rotation axis of the valve stem), and when the ball is located in the open position, the flow port is aligned to the seat, so that a medium flows through the ball valve.\",\n \"The ball is provided with a jack-up guide hole 31, in this example, the jack-up guide hole being a hexagonal hole.\",\n \"The axis X of the jack-up guide hole is perpendicular to the rotation axis Y of the ball and passes through the sphere center of the ball, and the axis of the jack-up guide hole is also perpendicular to the axis of the ball flow port.\",\n \"A lower trunnion 32 is disposed at the lower end of the ball, the lower trunnion being coaxial to the rotation axis of the ball, and a 90° fan-shaped projection 33 is disposed at the end of the lower trunnion.\",\n \"An upper trunnion 36 is disposed at the top of the ball, and a torsion spring pin hole 34 is disposed at the top of the upper trunnion.\",\n \"An intermediate transmission shaft 37 is disposed between the upper trunnion and the jack-up guide hole.\",\n \"The ball is provided with a ball-receiving surface 38 on the jack-up guide hole side, the ball-receiving surface being perpendicular to the axis of the jack-up guide hole.\",\n \"The sealing member 40 is part of ball, comprising a spherical surface 43 and a ball-receiving matching face 44, and the sealing member is provided with a jack-up threaded hole 42 in the center of the ball-receiving matching face side.\",\n \"The sealing member is constrained by means of linear movement against ball, a guide bar 41 is provided in the jack-up threaded hole, the guide bar is a hexagonal bar and in sliding fit with the jack-up guide hole 31 of the ball, so that the sealing member makes a reciprocating linear movement along the axis of the jack-up guide hole.\",\n \"The hexagonal shaft disables the sealing member from rotating with respect to the ball, so that the thread driving wheel drives the sealing member through the threads in linear movement.\",\n \"The thread driving wheel 60 is disposed on the ball, and the thread driving wheel is provided with a jack-up stud 61 which matches the jack-up threaded hole of the sealing member.\",\n \"The thread driving wheel is cut gear teeth 62, which is coaxial to the jack-up stud, the teeth 62 are conical teeth.\",\n \"The thread driving wheel is disposed on a shaft 39 of the ball through a locking ring 63.A sealing driving gear 70 is disposed on the valve stem, the sealing driving gear being a cone gear, and a polygonal hole 71 is disposed in the center of the sealing driving gear.\",\n \"An intermediate transmission gear 80 is disposed between the thread driving wheel and the sealing driving gear such that the intermediate transmission gear is located on the intermediate transmission shaft 37 of the ball, the intermediate transmission gear being also a cone gear, and the intermediate transmission gear is engaged with the sealing driving gear and the gear teeth of the thread driving wheel respectively, so that the valve stem drives the thread driving wheel to rotate via the sealing driving gear, and the thread driving wheel drives the sealing member towards the seat back and forth via matched threads in between.\",\n \"The ball is disposed within the valve body 11, the valve body is provided with a lower trunion chamber 12 corresponding to the lower trunion of the ball, the lower trunion chamber is provided with a 180-degree limiting slot 13 corresponding to the fan-shaped projection 33 at the bottom of the lower trunion of the ball.\",\n \"Thus, the rotation stroke of the ball is limited to 90°.\",\n \"The bottom of the valve stem is a polygon 23, and the top of sealing driving gear is in a driving mate with the bottom of the valve stem through the polygonal hole 71, so that the valve stem drives the sealing driving gear to rotate synchronously.\",\n \"During the valve closing operation, the single valve stem drives the ball to rotate through a torsion spring 50.The connection end of the valve stem is provided with a torsion spring shaft 21 which extends into the valve stem, with the torsion spring being sleeved on the torsion spring shaft, the valve stem is provided with a torsion spring pin hole 22, and the two torsion spring pins of the torsion spring are embedded in the torsion spring pin hole 22 of the valve stem and the torsion spring pin hole 34 of the ball respectively.\",\n \"It is desired that the torsion spring maintains a force on the ball, rotating the ball in the closing direction.\",\n \"Thus, when the ball is in the open position, the torsion spring applies a pre-driving force to the ball, rotating the ball towards the closing direction.\",\n \"With the driving mate between the valve stem and the sealing driving gear, the pre-driving force is transferred by the intermediate gear, so that thread driving gear drives the sealing member to tighten together against the ball, resulting in a balance.\",\n \"The seat is provided with a seal 15 that matches with the spherical surface of the sealing member to build up sealing, and when the ball is in the opening position, a rotation gap is provided between the seat and the ball.\",\n \"The valve stem drives the ball open and close.\",\n \"During the valve closing operation, the valve stem drives the ball to rotate via the torsion spring 50.When the ball rotates from the open position towards the close position, due to the pre-driving force applied to the ball by the torsion spring, the ball rotates in synchronization with the valve stem, avoiding the relative rotation between the sealing driving gear and the ball, so that the sealing member does not jack up from the ball.\",\n \"In the closed position, the ball stops rotating due to the fan-shaped projection 33 stop, while the valve stem keeps rotating towards the closing direction, so as to drive the sealing member to jack up the ball against the seat, resulting in the sealing contact between the spherical surface of the sealing member and the seal of the seat, thereby mechanical energized sealing is built.\",\n \"In the opening process of the valve, the valve stem rotates towards the opening direction and drives the sealing driving gear to rotate synchronously.\",\n \"Due to the force of the torsion spring, the ball does not rotate, and the sealing driving gear drives the sealing member to retract towards the ball, so that the ball-receiving matching face 44 of the sealing member is in contact with the ball-receiving surface 38 of the ball.\",\n \"The valve stem keeps rotating towards the opening direction, and as the sealing member is in contact with the ball, the sealing driving gear stops rotating with respect to the ball, so that the valve stem drives the ball and the sealing member to reach the opening position simultaneously.\",\n \"In order to ensure smooth open/close operation of the ball, after the sealing member retracts in place, the outer profile of the sealing member should not exceed the overall spherical profile of the ball, in this example, the outer profile of the sealing member and the outer profile of the ball form an integral spherical profile.\",\n \"Example 2 In this example, a mechanical energized sealing ball valve is provided, which is a structural modification of the mechanical energized sealing ball valve of Example 1.According to the mechanical energized sealing ball valve of this example, two sealing members are disposed on the ball and both mate with an upstream seat and a downstream seat.\",\n \"Example 3 In this example, a mechanical energized sealing ball valve is provided, which is a structural modification of the mechanical energized sealing ball valve of Example 1.A thread-driving wheel is disposed on a ball and connected with a sealing member through threads, and the thread driving wheel drives the sealing member to jack up the ball during rotating.\",\n \"The thread driving wheel is provided with a threaded hole, the sealing member is provided with a stud which matches threaded hole of the thread driving wheel.\",\n \"The thread driving wheel drives the sealing member to jack up and get back towards a seat through the threaded hole.\",\n \"Example 4 In this example, a mechanical energized sealing ball valve is provided, which is a structural modification of the mechanical energized sealing ball valve of Example 1.The sealing member is provided with a guide hole, the guide hole being a prismatic hole, the ball is provided with a guide shaft, the guide shaft being a prismatic shaft in sliding fit with the prismatic hole of the sealing member.\",\n \"Example 5 In this example, a mechanical energized sealing ball valve is provided, which is a structural modification of the mechanical energized sealing ball valve of Example 4.In this example, the ball and the sealing member are connected through a key shaft match, so that the sealing member jack up and get back towards the seat.\",\n \"Example 6 In this example, a mechanical energized sealing ball valve is provided, which is a structural modification of the mechanical energized sealing ball valve of Example 1 or Example 4.In this example, the ball and the sealing member are connected through a splined shaft match, so that the sealing member jack up and get back towards the seat.\",\n \"Example 7 In this example, a mechanical energized sealing ball valve is provided, which is a structural modification of the mechanical energized sealing ball valve of Example 1.The bottom of the valve stem is a spline, and the sealing driving gear top is provided with a splined hole which is engaged with the connection end of the valve stem.\",\n \"The sealing driving gear forms a driving mate with the bottom of the valve stem through the splined hole, so that the valve stem drives the sealing driving gear to rotate synchronously.\",\n \"Example 8 In this example, a mechanical energized sealing ball valve is provided, which is a structural modification of the mechanical energized sealing ball valve of Example 1.In this example, the valve body is side-entry body configuration.\",\n \"Example 9 In this example, a mechanical energized sealing ball valve is provided, which is a structural modification of the mechanical energized sealing ball valve of Example 1.In this example, the valve body is all-welded body configuration.\",\n \"Based on the basic principle of sealing, the invention fully solves the issues and concerns of the existing mechanical energized sealing ball valves.\",\n \"For example, the following issues and concerns are solved: relative sliding friction at the final stage of siting movement, insufficient normal component of sealing force of the seat, large structure and bulky size, need of hydraulic systems in certain designs, and potential damages caused by turbulence on the ball/plug assembly in case that the valve is in the open position in certain design.\",\n \"The invention adopts the design of trunnion mounted ball and stationary seat.\",\n \"A part of the ball assembly (for a plug valve, a part of the plug assembly), i.e., sealing member, is jacked towards the seat by the threaded jack-up mechanism, thereby build up sealing by mechanical energized force.\",\n \"The range of movement of the ball of the valve is limited by fine stop at the lower trunnion chamber of the valve body, thereby accurately stopped in 90-degree open/close position; with the torsion spring, the sealing member is tightened and locked against the ball in all other positions than the sealing position, so that 90 degree ball-seat friction free rotation can be achieved.\",\n \"In addition, the concern in the existing designs that sealing member and/or other parts attached to ball are damaged by turbulence is solved.\",\n \"After being aligned to the closing position, the ball stops rotating by fine stop of the lower trunnion, at this moment, the thread driving wheel is rotated by valve close torque transmitted by a set of gear mechanisms integrated to the ball, so that the sealing member is jacked up against seat firmly, and mechanical energized torque sealing is built.\",\n \"Such seating movement is evenly and aligning the normal vertical direction of the seat, so that there is no relative rotating/sliding friction between the sealing surfaces, thereby avoiding the relative sliding friction between the sealing surfaces at the final stage of the closing stroke of the conventional mechanical energized ball valves.\",\n \"With the principle of thread jack up configuration, the sealing member acts steadily and reliably, thereby ensuring the accuracy of siting between the sealing member and seat sealing surfaces.\",\n \"The valve has a compact structure which can conform to the standard face-to-face dimension, even may be shorter.\",\n \"The valve stem seal is a typical rotation stem seal configuration, which is uncomplicated and reliable.\",\n \"Only a single valve stem is needed to perform both the ball rotation, and sealing/unsealing, operations.\",\n \"Also, the time of valve open/close stroke is short.\",\n \"The invention has the innovation in the following aspects: Smoothly-operating sealing member thread jack-up mechanism; Aligning the same axial, the seat is positioned after the sealing member, after the thread driving wheel, after the ball.\",\n \"While closing the valve, thread driving wheel can only be energized by the operating torque and to rotate when the ball and the sealing member align to the seat, given the fact that the sealing member is guided by its hexagonal shaft, the sealing member is jacked up by thread driving wheel rather than being rotated together with the thread driving wheel, and sited against seat eventually, and mechanical energized sealing is built thereby.\",\n \"In this process, the thread jack-up action produces a sitting force perpendicular to the seat sealing surface, which avoids sliding friction as there is no any kind of rotation movement other than the jack-up press, sealing build-up is reliable and evenly.\",\n \"Again, the operations of changing the open and closed position, as well as sealed and unsealed position, require only a single valve stem.\",\n \"Feature of self-cleaning: While opening valve as the seat and the sealing member move apart evenly: on top of torsion spring force, valve open torque will drive valve open.\",\n \"It starts from the reverse rotation of the thread driving wheel, and due to the guide of the hexagonal shaft, the sealing member is disengaged from the seat rather than rotating together with the thread driving wheel, and finally locked tightly against the ball under the torsion spring force and the valve-opening torque, at this moment, the ball assembly will rotate until the valve is fully opened.\",\n \"In this process, the sealing member and the seat move apart evenly without any rotation movement in between the sealing member and the sea, and if foreign things are accumulated around the seat, the foreign things may be uniformly swept off by the medium at any angle, thereby it can be self-cleaned.\",\n \"The torque for opening/closing the valve is directly applied to the sealing driving gear through the valve stem.\",\n \"Before the sealing member and the seat are aligned, the gear set remains locked without rotation, and when the sealing member and the seat are aligned, the valve stem rotating torque firstly drives the sealing driving gear to rotate, then the torque is transferred to the thread driving wheel by the intermediate transmission gear, so that the thread driving wheel rotates the thread jack-up mechanism directly, thereby achieve mechanical energized sealing.\",\n \"By using the intermediate transmission gear for torque transferring, the size of the ball assembly can be greatly reduced, and thus greatly reduce the size of the whole valve.\",\n \"The torsion spring locking device functions interlink movement of the ball and the sealing driving gear: the torsion spring having a simple and reliable structure is disposed between the valve stem and the ball, The polygonal shaft at bottom of the valve stem is engaged with the polygonal hole at the top sealing driving gear to form the driving mate (alternatively, splined mate), once the sealing member and the ball are tightened by the gear set mechanism, an appropriate locking torque is applied to them by the torsion spring between the ball and valve stem, so that the sealing member and the ball are locked during the valve opening/closing stroke without contacting against the seat, to achieve friction-free ball rotation.\",\n \"While closing the valve, the sealing member and the seat are aligned, the rotation of the ball is stopped, valve-closing torque transferred through valve stem continuously will overcome the torsion spring force, so that the sealing driving gear rotates with respect to the ball to transfer the torque to the sealing member through the gear set mechanism to build up mechanical energized sealing.\",\n \"While opening the valve, the torsion spring will apply a torsion force to maintain the ball in the closing position, valve opening torque will drive the gear set mechanism and further drive sealing member to be tightened against the ball firstly, also the torsion spring will apply force on top to the valve closing torque to lock tightly the sealing member to the ball.\",\n \"The valve stem keeps rotating towards the valve opening direction, and the ball assembly rotates together with the valve stem until reaching the valve full-opening position.\",\n \"The torsion spring forms a simple-structure interlinked the movement of the valve stem, the ball and sealing driving gear, enables the ball assembly been tightened and locked in other positions than the full-closing position, as a result, the friction-free 90-degree rotation of the ball assembly is achieved, on the other hand, the potential damage of sealing member caused by the vibration due to turbulence of medium can be avoided when the valve is in full-open position.\",\n \"The mechanical stop at valve lower trunnion separates the joint movement of the ball and the sealing driving gear: Different from the conventional trunnion mounted ball valve, the lower trunnion of the ball is provided with a 90° fan-shaped projection, and the lower trunnion chamber of the valve body is provided with the 180° limiting slot corresponding to the lower trunnion of the ball.\",\n \"After the valve is assembled, the movement of the ball is strictly limited within the range of 90-degree open/close.\",\n \"When the ball is stopped at a closed position, valve closing torque applied by stem will overcome the force of torsion spring and drive gear set mechanism and rotate the threaded jack-up mechanism to achieve mechanical energized sealing.\"\n ]\n]"},"source":{"kind":"string","value":"Patent_15872000"}}},{"rowIdx":4493980,"cells":{"text":{"kind":"list like","value":[["Random Mat and Fiber-Reinforced Composite Material Shaped Product","There is provided a random mat including reinforcing fibers having an average fiber length of 3 to 100 mm and a thermoplastic resin, wherein the reinforcing fibers satisfy the following i) to iii).","i) The reinforcing fibers have a weight-average fiber width (Ww) which satisfies the following equation (1).","0 mm Background Art Random mats, which are isotropic, are used as fiber-reinforced composite materials in which carbon fibers, aramid fibers, glass fibers, and the like are used as reinforcing fibers, from the standpoints of formability and process simplicity.","These random mats can be obtained, for example, by the spray-up method (dry process) in which cut reinforcing fibers are blown into a shaping die either alone or simultaneously with a thermosetting resin or by a method (wet process) in which reinforcing fibers which have been cut in advance are added to a binder-containing slurry and this mixture is formed into a sheet by a papermaking method.","Known as a means for improving the mechanical properties of a composite material is to heighten the volume content ratio of reinforcing fibers (Vf).","In the case of random mats employing cut fibers, however, it has been difficult to heighten the volume content ratio of reinforcing fibers because of the presence of fibers oriented in three-dimensional directions, considerable fiber entanglement, etc.","Furthermore, in the case of using random mats, it is difficult to enable the reinforcing fibers to sufficiently exhibit the strength thereof since the fibers are discontinuous, as compared with the case where continuous fibers are used, and there has been a problem in that in a shaped product obtained, the development rate of strength of the reinforcing fibers is as low as up to 50% of the theoretical value.","Non-patent document 1 mentions a composite material produced from a carbon-fiber random mat employing a thermosetting resin as the matrix.","In this composite material, the development rate of strength is about 44% of the theoretical value.","In the case of conventional composite materials employing a thermosetting resin as the matrix, shaped products have been obtained from intermediate materials called prepregs, which were obtained by impregnating a reinforcing-fiber base material with a thermosetting resin in advance, by heating and pressing the intermediate materials for 2 hours or longer using an autoclave.","In recent years, an RTM method has been proposed in which a reinforcing-fiber base material impregnated with no resin is set in a mold and a thermosetting resin is then casted thereinto, and a remarkable reduction in shaping time has been attained.","However, even in the case of using the RTM method, 10 minutes or a longer period is required for each component to be shaped.","Consequently, composite materials obtained using a thermoplastic resin as the matrix, in place of the conventional thermosetting resin, are attracting attention.","Thermoplastic stamping (TP-SMC) in which a thermoplastic resin is used as the matrix (patent document 1) is a molding method which includes heating chopped fibers impregnated in advance with a thermoplastic resin to or above the melting point, introducing the heated fibers into some of the cavity of a mold, immediately closing the mold, and causing the fibers and the resin to flow within the mold to thereby obtain the shape of a product, followed by cooling and molding.","In this technique, molding can be completed in a period as short as about 1 minute by using fibers impregnated with a resin in advance.","Such techniques are methods in which molding materials called SMCs or stampable sheets are used.","The thermoplastic stamping has had problems, for example, in that since the fibers and the resin are caused to flow within the mold, thin-walled products cannot be molded and fiber orientation is disordered and difficult to control.","Patent document 2 proposes, as a means for improving mechanical properties and the isotropy in a fiber-reinforced thermoplastic resin shaped product, a technique wherein constituent carbon fibers are evenly dispersed into a single fiber form to thereby avoid the trouble that resin-rich portions are formed at the spaces between fiber bundles or that the resin cannot be impregnated into inner parts of fiber bundles, resulting in unimpregnated portions, and to thereby improve mechanical properties and the isotropy thereof."],[" SUMMARY OF THE INVENTION "],["CROSS REFERENCE TO RELATED APPLICATIONS This application is a continuation of U.S. application Ser.","No.","14/382,136, filed Aug. 29, 2014, which is a U.S. National Phase Application under 35 U.S.C.","§ 371 of International Application No.","PCT/JP2013/070604, filed Jul.","30, 2013, which claims priority to Japanese Application 2012-169936 filed Jul.","31, 2012, and which was published Under PCT Article 21(2), the entire contents of which are incorporated herein by reference.","Technical Field The present invention relates to a random mat for use as an intermediate material for fiber-reinforced composite material shaped products in which a thermoplastic resin is used as the matrix, and to a fiber-reinforced composite material shaped product obtained from the random mat.","Background Art Random mats, which are isotropic, are used as fiber-reinforced composite materials in which carbon fibers, aramid fibers, glass fibers, and the like are used as reinforcing fibers, from the standpoints of formability and process simplicity.","These random mats can be obtained, for example, by the spray-up method (dry process) in which cut reinforcing fibers are blown into a shaping die either alone or simultaneously with a thermosetting resin or by a method (wet process) in which reinforcing fibers which have been cut in advance are added to a binder-containing slurry and this mixture is formed into a sheet by a papermaking method.","Known as a means for improving the mechanical properties of a composite material is to heighten the volume content ratio of reinforcing fibers (Vf).","In the case of random mats employing cut fibers, however, it has been difficult to heighten the volume content ratio of reinforcing fibers because of the presence of fibers oriented in three-dimensional directions, considerable fiber entanglement, etc.","Furthermore, in the case of using random mats, it is difficult to enable the reinforcing fibers to sufficiently exhibit the strength thereof since the fibers are discontinuous, as compared with the case where continuous fibers are used, and there has been a problem in that in a shaped product obtained, the development rate of strength of the reinforcing fibers is as low as up to 50% of the theoretical value.","Non-patent document 1 mentions a composite material produced from a carbon-fiber random mat employing a thermosetting resin as the matrix.","In this composite material, the development rate of strength is about 44% of the theoretical value.","In the case of conventional composite materials employing a thermosetting resin as the matrix, shaped products have been obtained from intermediate materials called prepregs, which were obtained by impregnating a reinforcing-fiber base material with a thermosetting resin in advance, by heating and pressing the intermediate materials for 2 hours or longer using an autoclave.","In recent years, an RTM method has been proposed in which a reinforcing-fiber base material impregnated with no resin is set in a mold and a thermosetting resin is then casted thereinto, and a remarkable reduction in shaping time has been attained.","However, even in the case of using the RTM method, 10 minutes or a longer period is required for each component to be shaped.","Consequently, composite materials obtained using a thermoplastic resin as the matrix, in place of the conventional thermosetting resin, are attracting attention.","Thermoplastic stamping (TP-SMC) in which a thermoplastic resin is used as the matrix (patent document 1) is a molding method which includes heating chopped fibers impregnated in advance with a thermoplastic resin to or above the melting point, introducing the heated fibers into some of the cavity of a mold, immediately closing the mold, and causing the fibers and the resin to flow within the mold to thereby obtain the shape of a product, followed by cooling and molding.","In this technique, molding can be completed in a period as short as about 1 minute by using fibers impregnated with a resin in advance.","Such techniques are methods in which molding materials called SMCs or stampable sheets are used.","The thermoplastic stamping has had problems, for example, in that since the fibers and the resin are caused to flow within the mold, thin-walled products cannot be molded and fiber orientation is disordered and difficult to control.","Patent document 2 proposes, as a means for improving mechanical properties and the isotropy in a fiber-reinforced thermoplastic resin shaped product, a technique wherein constituent carbon fibers are evenly dispersed into a single fiber form to thereby avoid the trouble that resin-rich portions are formed at the spaces between fiber bundles or that the resin cannot be impregnated into inner parts of fiber bundles, resulting in unimpregnated portions, and to thereby improve mechanical properties and the isotropy thereof.","CITATION LIST Patent Documents Patent Document 1: Japanese Patent No.","4161409 Patent Document 2: International Publication WO 2007/097436 Non-Patent Document Non-Patent Document 1: Composites, Part A 38 (2007) pp.755-770 SUMMARY OF THE INVENTION Problems that the Invention is to Solve However, in the conventional-art techniques described above, no investigations have been made on a fiber-reinforced composite material shaped product which is even in mechanical strength, has excellent tensile strength, and has a high development rate of strength relative to a theoretical strength.","An objective of the invention is to provide a fiber-reinforced composite material shaped product which is isotropic and has excellent mechanical strength and a random mat for use as an intermediate material therefor.","In particular, the invention is to provide a fiber-reinforced composite material shaped product which is a fiber-reinforced composite material shaped product obtained from the random mat and in which the reinforcing-fiber mat included therein has small unevenness of thickness, is even in mechanical strength, and has excellent tensile strength and a high development rate of strength.","Means for Solving the Problems The present inventors have found that a fiber-reinforced composite material shaped product which is excellent in terms of mechanical strength, isotropy thereof, and strength development can be provided by a random mat which includes both a thermoplastic resin and discontinuous reinforcing fibers having specific values of weight-average fiber width, average-fiber-width dispersion ratio, and weight-average fiber thickness.","The invention has been thus completed.","More specifically, the inventors have found that by regulating reinforcing fibers so as to be small and be similar in fiber width, the reinforcing fibers can be densely incorporated into a random mat and a fiber-reinforced composite material shaped product which is even and has excellent mechanical strength and a high development rate of strength can be provided.","Namely, the present invention is: a random mat which includes reinforcing fibers having an average fiber length of 3-100 mm and a thermoplastic resin, wherein the reinforcing fibers satisfy the following i) to iii); and a fiber-reinforced composite material shaped product obtained by shaping the random mat.","i) The reinforcing fibers have a weight-average fiber width (Ww) which satisfies the following equation (1).","0 mm Background Art Random mats, which are isotropic, are used as fiber-reinforced composite materials in which carbon fibers, aramid fibers, glass fibers, and the like are used as reinforcing fibers, from the standpoints of formability and process simplicity.\",\n \"These random mats can be obtained, for example, by the spray-up method (dry process) in which cut reinforcing fibers are blown into a shaping die either alone or simultaneously with a thermosetting resin or by a method (wet process) in which reinforcing fibers which have been cut in advance are added to a binder-containing slurry and this mixture is formed into a sheet by a papermaking method.\",\n \"Known as a means for improving the mechanical properties of a composite material is to heighten the volume content ratio of reinforcing fibers (Vf).\",\n \"In the case of random mats employing cut fibers, however, it has been difficult to heighten the volume content ratio of reinforcing fibers because of the presence of fibers oriented in three-dimensional directions, considerable fiber entanglement, etc.\",\n \"Furthermore, in the case of using random mats, it is difficult to enable the reinforcing fibers to sufficiently exhibit the strength thereof since the fibers are discontinuous, as compared with the case where continuous fibers are used, and there has been a problem in that in a shaped product obtained, the development rate of strength of the reinforcing fibers is as low as up to 50% of the theoretical value.\",\n \"Non-patent document 1 mentions a composite material produced from a carbon-fiber random mat employing a thermosetting resin as the matrix.\",\n \"In this composite material, the development rate of strength is about 44% of the theoretical value.\",\n \"In the case of conventional composite materials employing a thermosetting resin as the matrix, shaped products have been obtained from intermediate materials called prepregs, which were obtained by impregnating a reinforcing-fiber base material with a thermosetting resin in advance, by heating and pressing the intermediate materials for 2 hours or longer using an autoclave.\",\n \"In recent years, an RTM method has been proposed in which a reinforcing-fiber base material impregnated with no resin is set in a mold and a thermosetting resin is then casted thereinto, and a remarkable reduction in shaping time has been attained.\",\n \"However, even in the case of using the RTM method, 10 minutes or a longer period is required for each component to be shaped.\",\n \"Consequently, composite materials obtained using a thermoplastic resin as the matrix, in place of the conventional thermosetting resin, are attracting attention.\",\n \"Thermoplastic stamping (TP-SMC) in which a thermoplastic resin is used as the matrix (patent document 1) is a molding method which includes heating chopped fibers impregnated in advance with a thermoplastic resin to or above the melting point, introducing the heated fibers into some of the cavity of a mold, immediately closing the mold, and causing the fibers and the resin to flow within the mold to thereby obtain the shape of a product, followed by cooling and molding.\",\n \"In this technique, molding can be completed in a period as short as about 1 minute by using fibers impregnated with a resin in advance.\",\n \"Such techniques are methods in which molding materials called SMCs or stampable sheets are used.\",\n \"The thermoplastic stamping has had problems, for example, in that since the fibers and the resin are caused to flow within the mold, thin-walled products cannot be molded and fiber orientation is disordered and difficult to control.\",\n \"Patent document 2 proposes, as a means for improving mechanical properties and the isotropy in a fiber-reinforced thermoplastic resin shaped product, a technique wherein constituent carbon fibers are evenly dispersed into a single fiber form to thereby avoid the trouble that resin-rich portions are formed at the spaces between fiber bundles or that the resin cannot be impregnated into inner parts of fiber bundles, resulting in unimpregnated portions, and to thereby improve mechanical properties and the isotropy thereof.\"\n ],\n [\n \" SUMMARY OF THE INVENTION \"\n ],\n [\n \"CROSS REFERENCE TO RELATED APPLICATIONS This application is a continuation of U.S. application Ser.\",\n \"No.\",\n \"14/382,136, filed Aug. 29, 2014, which is a U.S. National Phase Application under 35 U.S.C.\",\n \"§ 371 of International Application No.\",\n \"PCT/JP2013/070604, filed Jul.\",\n \"30, 2013, which claims priority to Japanese Application 2012-169936 filed Jul.\",\n \"31, 2012, and which was published Under PCT Article 21(2), the entire contents of which are incorporated herein by reference.\",\n \"Technical Field The present invention relates to a random mat for use as an intermediate material for fiber-reinforced composite material shaped products in which a thermoplastic resin is used as the matrix, and to a fiber-reinforced composite material shaped product obtained from the random mat.\",\n \"Background Art Random mats, which are isotropic, are used as fiber-reinforced composite materials in which carbon fibers, aramid fibers, glass fibers, and the like are used as reinforcing fibers, from the standpoints of formability and process simplicity.\",\n \"These random mats can be obtained, for example, by the spray-up method (dry process) in which cut reinforcing fibers are blown into a shaping die either alone or simultaneously with a thermosetting resin or by a method (wet process) in which reinforcing fibers which have been cut in advance are added to a binder-containing slurry and this mixture is formed into a sheet by a papermaking method.\",\n \"Known as a means for improving the mechanical properties of a composite material is to heighten the volume content ratio of reinforcing fibers (Vf).\",\n \"In the case of random mats employing cut fibers, however, it has been difficult to heighten the volume content ratio of reinforcing fibers because of the presence of fibers oriented in three-dimensional directions, considerable fiber entanglement, etc.\",\n \"Furthermore, in the case of using random mats, it is difficult to enable the reinforcing fibers to sufficiently exhibit the strength thereof since the fibers are discontinuous, as compared with the case where continuous fibers are used, and there has been a problem in that in a shaped product obtained, the development rate of strength of the reinforcing fibers is as low as up to 50% of the theoretical value.\",\n \"Non-patent document 1 mentions a composite material produced from a carbon-fiber random mat employing a thermosetting resin as the matrix.\",\n \"In this composite material, the development rate of strength is about 44% of the theoretical value.\",\n \"In the case of conventional composite materials employing a thermosetting resin as the matrix, shaped products have been obtained from intermediate materials called prepregs, which were obtained by impregnating a reinforcing-fiber base material with a thermosetting resin in advance, by heating and pressing the intermediate materials for 2 hours or longer using an autoclave.\",\n \"In recent years, an RTM method has been proposed in which a reinforcing-fiber base material impregnated with no resin is set in a mold and a thermosetting resin is then casted thereinto, and a remarkable reduction in shaping time has been attained.\",\n \"However, even in the case of using the RTM method, 10 minutes or a longer period is required for each component to be shaped.\",\n \"Consequently, composite materials obtained using a thermoplastic resin as the matrix, in place of the conventional thermosetting resin, are attracting attention.\",\n \"Thermoplastic stamping (TP-SMC) in which a thermoplastic resin is used as the matrix (patent document 1) is a molding method which includes heating chopped fibers impregnated in advance with a thermoplastic resin to or above the melting point, introducing the heated fibers into some of the cavity of a mold, immediately closing the mold, and causing the fibers and the resin to flow within the mold to thereby obtain the shape of a product, followed by cooling and molding.\",\n \"In this technique, molding can be completed in a period as short as about 1 minute by using fibers impregnated with a resin in advance.\",\n \"Such techniques are methods in which molding materials called SMCs or stampable sheets are used.\",\n \"The thermoplastic stamping has had problems, for example, in that since the fibers and the resin are caused to flow within the mold, thin-walled products cannot be molded and fiber orientation is disordered and difficult to control.\",\n \"Patent document 2 proposes, as a means for improving mechanical properties and the isotropy in a fiber-reinforced thermoplastic resin shaped product, a technique wherein constituent carbon fibers are evenly dispersed into a single fiber form to thereby avoid the trouble that resin-rich portions are formed at the spaces between fiber bundles or that the resin cannot be impregnated into inner parts of fiber bundles, resulting in unimpregnated portions, and to thereby improve mechanical properties and the isotropy thereof.\",\n \"CITATION LIST Patent Documents Patent Document 1: Japanese Patent No.\",\n \"4161409 Patent Document 2: International Publication WO 2007/097436 Non-Patent Document Non-Patent Document 1: Composites, Part A 38 (2007) pp.755-770 SUMMARY OF THE INVENTION Problems that the Invention is to Solve However, in the conventional-art techniques described above, no investigations have been made on a fiber-reinforced composite material shaped product which is even in mechanical strength, has excellent tensile strength, and has a high development rate of strength relative to a theoretical strength.\",\n \"An objective of the invention is to provide a fiber-reinforced composite material shaped product which is isotropic and has excellent mechanical strength and a random mat for use as an intermediate material therefor.\",\n \"In particular, the invention is to provide a fiber-reinforced composite material shaped product which is a fiber-reinforced composite material shaped product obtained from the random mat and in which the reinforcing-fiber mat included therein has small unevenness of thickness, is even in mechanical strength, and has excellent tensile strength and a high development rate of strength.\",\n \"Means for Solving the Problems The present inventors have found that a fiber-reinforced composite material shaped product which is excellent in terms of mechanical strength, isotropy thereof, and strength development can be provided by a random mat which includes both a thermoplastic resin and discontinuous reinforcing fibers having specific values of weight-average fiber width, average-fiber-width dispersion ratio, and weight-average fiber thickness.\",\n \"The invention has been thus completed.\",\n \"More specifically, the inventors have found that by regulating reinforcing fibers so as to be small and be similar in fiber width, the reinforcing fibers can be densely incorporated into a random mat and a fiber-reinforced composite material shaped product which is even and has excellent mechanical strength and a high development rate of strength can be provided.\",\n \"Namely, the present invention is: a random mat which includes reinforcing fibers having an average fiber length of 3-100 mm and a thermoplastic resin, wherein the reinforcing fibers satisfy the following i) to iii); and a fiber-reinforced composite material shaped product obtained by shaping the random mat.\",\n \"i) The reinforcing fibers have a weight-average fiber width (Ww) which satisfies the following equation (1).\",\n \"0 mm BACKGROUND INFORMATION Early contact lenses have been known with photochromic liquid held in a reservoir disposed between two materials forming a contact lens as part of a protective system against intense flashes such as a nuclear detonation.","More recently, efforts have been directed towards photochromic contact lenses that can be worn daily and that quickly transition between colored and uncolored states utilizing photochromic dyes capable of absorbing light in specific wavelength ranges.","In some examples, a dye is dispensed in a lens capable of exhibiting photochromism in the polymeric material comprising the contact lens so as to preferably have a single layer capable of absorbing light.","However the contact lenses that exhibit photochromism throughout the entire lens area, “edge-to-edge”, are not desired due to cosmetic reasons.","Therefore, efforts have been made to create a contact lens that changes color only in the central pupil region, “pupil-only” contact lens.","US2003/0142267 discloses contact lenses having a photochromic material in the center or pupil region of the lens only.","The lens is made by dispensing monomer mixes having different viscosities into the lens mold.","The contact lenses are hard contact lenses which have no water content.","The process disclosed in US2003/0142267 does not produce soft, hydrogel contact lenses which have desirable properties such as good optics and comfort.","There is a need for an improved pupil only photochromic contact lens, including a method of manufacturing such lenses, that exhibits reduced deformation and optical distortion and increased comfort, wear ability, and cosmetic appearance."],[" BRIEF DESCRIPTION OF THE DRAWINGS The present invention is disclosed with reference to the accompanying drawings, wherein: FIGS.","1A and 1B schematically represent methods of making pupil only photochromic lenses according to the invention.","FIG.","2 is an exemplary lens made according to the methods of the invention.","FIG.","3 shows an interferogram of a contact lens according to the invention.","FIG.","4 is an exemplary lens according to the invention.","FIGS.","5-8 are photographs of the lenses of Examples 12, Comparative Examples 1 and 2 and Example 13.FIG.","9 is a schematic of the apparatus used to measure the deviation of sagittal depth from the design sagittal depth in the examples.","detailed-description description=\"Detailed Description\" end=\"lead\"?"],["RELATED APPLICATIONS This application claims priority to provisional U.S. patent application Ser.","No.","61/323,410, filed Apr.","13, 2010.TECHNICAL FIELD The present invention relates to contact lens eyewear and, more particularly, to contact lenses with photochromic dyes disposed in the region of the lens covering the pupil region when worn, the photochromic contact lenses having improved cosmetic appearance and improved structural qualities.","The invention also relates to methods and materials used for making such photochromic contact lenses.","BACKGROUND INFORMATION Early contact lenses have been known with photochromic liquid held in a reservoir disposed between two materials forming a contact lens as part of a protective system against intense flashes such as a nuclear detonation.","More recently, efforts have been directed towards photochromic contact lenses that can be worn daily and that quickly transition between colored and uncolored states utilizing photochromic dyes capable of absorbing light in specific wavelength ranges.","In some examples, a dye is dispensed in a lens capable of exhibiting photochromism in the polymeric material comprising the contact lens so as to preferably have a single layer capable of absorbing light.","However the contact lenses that exhibit photochromism throughout the entire lens area, “edge-to-edge”, are not desired due to cosmetic reasons.","Therefore, efforts have been made to create a contact lens that changes color only in the central pupil region, “pupil-only” contact lens.","US2003/0142267 discloses contact lenses having a photochromic material in the center or pupil region of the lens only.","The lens is made by dispensing monomer mixes having different viscosities into the lens mold.","The contact lenses are hard contact lenses which have no water content.","The process disclosed in US2003/0142267 does not produce soft, hydrogel contact lenses which have desirable properties such as good optics and comfort.","There is a need for an improved pupil only photochromic contact lens, including a method of manufacturing such lenses, that exhibits reduced deformation and optical distortion and increased comfort, wear ability, and cosmetic appearance.","BRIEF DESCRIPTION OF THE DRAWINGS The present invention is disclosed with reference to the accompanying drawings, wherein: FIGS.","1A and 1B schematically represent methods of making pupil only photochromic lenses according to the invention.","FIG.","2 is an exemplary lens made according to the methods of the invention.","FIG.","3 shows an interferogram of a contact lens according to the invention.","FIG.","4 is an exemplary lens according to the invention.","FIGS.","5-8 are photographs of the lenses of Examples 12, Comparative Examples 1 and 2 and Example 13.FIG.","9 is a schematic of the apparatus used to measure the deviation of sagittal depth from the design sagittal depth in the examples.","DETAILED DESCRIPTION As used herein hydrogels are water swellable polymers which have water contents between about 20 and about 75% water.","As used herein reactive mixture or monomer mixture means As used herein, expansion factor or swell is the change in dimension of a hydrogel article after hydration.","Expansion factor may be calculated by dividing the diameter of hydrated lens by the lens formed in the mold prior to extraction and hydration and multiplying by 100.As used herein sagittal depth is the height of a contact lens, measured at its center (vertex) and from a chord drawn across the lens at its base diameter.","Known tests may be used to measure sagittal depth, including ISO 18369-3, using an ultrasound instrument (section 4.1.4.2.3).","Generally, one way to manufacture soft, hydrogel contact lenses is to cast mold contact lenses in plastic molds.","Typically there are two mold portions which, when assembled, form a cavity.","A reactive mixture which cures within the cavity forms a contact lens.","Typically a first mold portion is dosed with the reactive mixture, and the second mold portion is placed on the first mold portion, and then the reactive mixture is cured.","The reaction of the reactive mixture is commonly radiation activated.","The reactive mixture in the cavity cures e.g.","polymerizes and/or crosslinks to form the contact lens.","The cured hydrogel contact lens is then removed from the molds and put in a solvent to remove the undesired chemical components.","The lens normally swells in the process.","The lens is then brought into contact with water to exchange the solvent with water, and give the hydrogel its final, stable shape and size.","Specifically referring to FIG.","1, two methods of manufacturing pupil only photochromic contact lenses are schematically shown.","In the first method shown in FIG.","1a, a front curve 11a is provided at step 10a.","The front curve 11a is one part of the two part mold that is concave in shape so that the deposited material is held in the center of the mold by gravity.","At step 12a, a small and precise dose of photochromic dye-containing monomer mixture 13a, or pupil monomer mixture, is supplied or dosed on a surface of the front curve mold 11a preferably in a substantially central location and in substantially circular configuration.","In one embodiment, the photochromic dye-containing monomer mixture is dosed in a central circular area within the optic zone of the contact lens.","The central circular area may be the same size as the optic zone, which in a typical contact lens is about 9 mm or less in diameter.","In one embodiment, the central circular area has a diameter of between about 4 and about 7 mm and in another between about 4 and about 6 mm in diameter.","Optionally, the photochromic dye-containing monomer mixture may be at least partially polymerized through a controlled curing mechanism at step 12a.","Then, a dose of clear monomer mixture, which does not contain a photochromic dye, 15a is dosed on the top of the photochromic dye-containing monomer mixture 13a at step 14a.","The dose of clear monomer mixture 15a fills the concave front curve 11a to the desired amount and then, at step 16a, the base curve 17a is provided and the mold halves 11a, 17a are put into their final curing position and the monomer mixtures are cured and/or polymerized completing the molding process.","Where the polymerization process includes a photo-polymerization mechanism, the radiation, may be directed to either the front curve mold half or the base curve mold half, or both.","The molded lens is then extracted to remove the un-desired chemical components and hydrated.","An alternative method is shown in FIG.","1b in which the first dose of photochromic monomer mixture 13b is provided in the center of a front curve mold 11b at step 12b and then an annular ring of clear monomer mixture 15b is dosed at the edge of the front curve mold 11b at step 14b.","The resultant annular ring of clear monomeric material 15b is drawn to the center of the front curve by gravity.","The base curve mold 17b is then supplied and the curing is initiated and completed at step 16b and the extraction and hydration step(s) (not shown) proceed to form the final hydrogel contact lens product.","In order to provide a hydrogel contact lens with acceptable separation of the two regions (print quality) and low distortion, generally in terms of centralized photochromic dye 11 distribution, it has been found that, as described by US2003/0142267, increasing the viscosities of the monomer mixtures 13, 15 and, specifically, increasing the viscosity of the photochromic dye monomer mixture 13 as compared to the clear monomer mixture 15, reduces molecular diffusion of the monomers 13, 15 thereby maintaining photochromic dye in the central region.","Using a photochromic dye monomer mixture that has higher viscosity than the clear monomer mixture helps to reduce the shear at the interface of the two monomers mixtures thereby reducing the physical mixing.","An analysis of the Stokes-Einstein equation, shown below, illustrates the parameters that affect the diffusivity of a material: D = kT 6 πμ r where, D is the molecular diffusivity, k the Boltzmann constant, T the temperature, μ the viscosity and r the radius of the molecule.","Operating at lower temperatures and using monomers of higher viscosities tends to reduce the molecular diffusion rate.","In one embodiment the viscosity of the photochromic dye monomer mixture is at least about 1000 cp higher than the viscosity of the clear or peripheral monomer mixture and in another embodiment at least about 1500 cp higher.","However, controlling the viscosity of the monomer mixtures as disclosed in US2003/0142267 was insufficient to provide hydrogel contact lenses having suitable optics and comfort.","Hydrogel monomer mixtures when cured together produced contact lenses which displayed flattened optic zones, instead of lenses with a continuous radius.","This may be measured by measuring the sagittal depth of the contact lens.","Hydrogel lenses of the present invention have sagittal depths which are within about 100 microns of the design sagittal depth for the lens.","In one embodiment the deviation from the design sagittal depth ranges from 0 (matched to the design sagittal depth) to −100 microns, which represents a slight flattening from the design sagittal depth.","It has been found that by balancing the expansion factor of the polymers formed from the photochromic dye monomer mixture and the clear monomer mixture hydrogel contact lenses having desirable optics and comfort may be produced.","In one embodiment the expansion factors of the polymers formed from the respective monomer mixtures are within about 10% in some embodiments within about 8% and in other embodiments within about 5%.","The expansion factor may be adjusted by manipulating a number of formulation variables including the diluent concentration, the concentration and hydrophilicity or hydrophobicity of hydrophilic and hydrophobic components and concentration of initiator and crosslinker, and combinations thereof.","Many photochromic dyes are highly hydrophobic and at the concentrations used in the present invention can have an impact on the expansion factor the hydrogels which contain them.","In one embodiment, where the photochromic dye is hydrophobic, it is added to the formulation replacing a similar amount of another hydrophobic component.","Similarly, if the photochromic compound were hydrophilic it will be added to the formulation replacing a similar amount of another hydrophilic component.","In some embodiments, for example, where a silicone hydrogel contact lens is being produced, it may be desirable to maintain the concentration of the silicone components and replace a part of one of hydrophilic components.","In these embodiments, multiple adjustments may be needed to achieve the desired expansion factor.","In addition, other formulation variables may be modified to achieve the desired expansion factor.","In some embodiments varying the concentration of the hydrophilic components, the diluent concentration and the initiator concentration, and combinations thereof have been effective at providing photochromic contact lenses having desirable optics and comfort.","In one embodiment a hydrophilic polymer, such as poly(vinyl pyrrolidone) (PVP), methacrylic acid, polydimethylacrylamide or poly(vinyl methacetamide) may be added to the photochromic dye monomer mixture.","In some embodiments it is desirable to use the same or similar components in both the photochromic dye and clear monomer mixtures.","For example, it may be desirable to include the same hydrophilic components in both monomer mixtures.","In this case, formulation variables in addition to the concentration of hydrophilic components may be varied.","The examples further illustrate how the formulation variables may be balanced.","In one embodiment, where a single sided cure is used the expansion factor is matched using monomers, diluent concentration and combinations thereof.","Where cure is effected from only one side (such as during photocuring), increasing the initiator concentration may also be desirable.","The clear monomer mixtures 15 that may be employed in the invention include soft contact lens materials made from HEMA based hydrogel or silicone hydrogel materials, which include but are not limited to silicone hydrogels, and fluorohydrogels.","Examples of soft contact lenses formulations include but are not limited to the formulations of etafilcon A, genfilcon A, lenefilcon A, polymacon, acquafilcon A, balafilcon A, galyfilcon A, senofilcon, narafilcon A, narafilcon B, comfilcon, filcon II 3, asmofilcon, Monomer A and lotrafilcon A, and the like.","Silicone hydrogels formulations, such as those disclosed in U.S. Pat.","No.","5,998,498; U.S. patent app.","Ser.","No.","09/532,943, a continuation-in-part of U.S. patent app.","Ser.","No.","09/532,943, filed on Aug. 30, 2000, and U.S. Pat.","No.","6,087,415, U.S. Pat.","No.","6,087,415, U.S. Pat.","No.","5,760,100, U.S. Pat.","No.","5,776,999, U.S. Pat.","No.","5,789,461, U.S. Pat.","No.","5,849,811, U.S. Pat.","No.","5,965,631, U.S. Pat.","No.","7,553,880, W02008/061992,US2010/048847, may also be used.","These patents are hereby incorporated by reference for the hydrogel compositions contained therein.","In one embodiment contact lens formulations are selected from etafilcon A, balafilcon A, acquafilcon A, lotrafilcon A, galyfilcon A, senfilcon, comfilcon, narafilcon, Monomer A and silicone hydrogels.","Additionally, suitable contact lenses may be formed from reaction mixtures comprising at least one silicone containing component.","A silicone-containing component is one that contains at least one [—Si—O—Si] group, in a monomer, macromer or prepolymer.","Preferably, the Si and attached 0 are present in the silicone-containing component in an amount greater than 20 weight percent, and more preferably greater than 30 weight percent of the total molecular weight of the silicone-containing component.","Useful silicone-containing components preferably comprise polymerizable functional groups such as acrylate, methacrylate, acrylamide, methacrylamide, N-vinyl lactam, N-vinylamide, and styryl functional groups.","Examples of silicone components which may be included in the silicone hydrogel formulations include, but are not limited to silicone macromers, prepolymers and monomers.","Examples of silicone macromers include, without limitation, polydimethylsiloxane methacrylated with pendant hydrophilic groups.","Silicone and/or fluorine containing macromers may also be used.","Suitable silicone monomers include tris(trimethylsiloxy)silylpropyl methacrylate, hydroxyl functional silicone containing monomers, such as 3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane.. Additional suitable siloxane containing monomers include, amide analogs of TRIS.","Vinylcarbanate or carbonate analogs, monomethacryloxypropyl terminated polydimethylsiloxanes, polydimethylsiloxanes, 3-methacryloxypropylbi s(trimethyl siloxy)methyl silane, methacryloxypropylpentamethyl disiloxane and combinations thereof.","Exemplary photochromic materials that may be employed in some embodiments may include dyes mixed with contact lens materials, or alternately, polymerizeable monomers that are themselves photochromic.","Other exemplary materials may include one or more of the following: polymerizable photochromic materials, such as polymerizable naphthoxazines; polymerizable spirobenzopyrans; polymerizable spirobenzopyrans and spirobenzothiopyrans; polymerizable fulgides; polymerizable naphthacenediones; polymerizable spirooxazines; polymerizable polyalkoxylated naphthopyrans; and polymerizable photochromic compounds.","Furthermore the photochromic materials may include in some embodiments, one or more of the following classes of materials: chromenes, e.g., naphthopyrans, benzopyrans, indenonaphthopyrans and phenanthropyrans; spiropyrans, e.g., spiro(benzindoline)naphthopyrans, spiro(indoline)benzopyrans, spiro(indoline)naphthopyrans, spiro(indoline)quinopyrans and spiro(indoline)pyrans; oxazines, e.g., spiro(indoline)naphthoxazines, spiro(indoline)pyridobenzoxazines, spiro(benzindoline)pyridobenzoxazines, spiro(benzindoline)naphthoxazines and spiro(indoline)benzoxazines; mercury dithizonates, fulgides, fulgimides and mixtures of such photochromic compounds.","Other photochromic materials that may be useful in the invention include organo-metal dithiozonates, i.e., (arylazo)-thioformic arylhydrazidates, e.g., mercury dithizonates; and fulgides and fulgimides, e.g., the 3-furyl and 3-thienyl fulgides and fulgimides.","Non-limiting examples of suitable photochromic dyes include The following examples and experiments illustrate certain aspects of the present invention, but they do not delineate or limit the invention.","EXAMPLES The following abbreviations are used in the examples below: Abbreviation Full Chemical Name SiGMA 2-propenoic acid, 2-methyl-,2-hydroxy-3-[3-[1,3,3,3- tetramethyl-1- [(trimethylsilyl)oxy]disiloxanyl]propoxy]propyl ester HEMA 2-hydroxyethyl methacrylate mPDMS 800-1000 MW (Mn) monomethacryloxypropyl terminated mono-n-butyl terminated polydimethylsiloxane DMA N,N-dimethylacrylamide PVP poly(N-vinyl pyrrolidone) (K value 90) Norbloc 2-(2′-hydroxy-5-methacrylyloxyethylphenyl)-2H- benzotriazole CGI 819 1:1 (wgt) blend of 1-hydroxycyclohexyl phenyl ketone and bis(2,6-dimethoxybenzoyl)-2,4-4-trimethylpentyl phosphine oxide Blue HEMA the reaction product of Reactive Blue 4 and HEMA IPA isopropyl alcohol D30 3,7-dimethyl-3-octanol mPDMS— mono-(3-methacryloxy-2-hydroxypropyloxy)propyl OH terminated, mono-butyl terminated polydimethylsiloxane (MW 1100) TEGDMA tetraethyleneglycol dimethacrylate TPME tripropylene glycol methyl ether Monomer Mixture A Monomer mixture A was formed from the components listed in Table 1 and diluent (D30) (77 wt % components:23 wt % D30).","TABLE 1 Components Wt % SiGMA 28 PVP (K90) 7 DMA 24 mPDMS 31 HEMA 6 Norbloc 2 CGI 1850 0.48 TEGDMA 1.5 Blue HEMA 0.02 Monomer Mixture B Monomer mixture B was formed from the 55 wt % components listed in Table 1 and 45 wt % diluent (a mixture of 55 wt % TPME and 45 wt % decanoic acid co-diluent).","TABLE 2 Monomer Components Monomers wt.","% HO—mPDMS 55 TEGDMA 3 DMA 19.53 HEMA 8.00 PVP K-90 12 CGI 819 0.25 Norbloc 2.2 Blue HEMA 0.02 The Monomer mixture B formulations were degassed at about 600-700 mmHg for approximately 30 minutes at ambient temperature prior to dosing.","Example 1 To demonstrate the feasibility for obtaining a pupil-only contact lens according to the method of FIG.","1a, 20 mg ball-pen ink was mixed into 1 g Monomer B monomer mixture listed in Table 2 to simulate the dye-containing pupil monomer and 3 mg of this monomer mixture was dosed into the center of a front curve mold 10c.","The viscosity of the monomer mixture was ˜3000 CP.","Next, 80 mg of Monomer A monomer mixture was dosed on top of the pupil monomer mixture as shown in 14c.","The viscosity of the Monomer A monomer mixture was ˜300 CP.","A base curve was then deposited and the molds were closed and irradiated at 1.2 to 1.8 mW/cm2, under Philips TL K 40 W/03 light bulbs in a nitrogen atmosphere for 25 minutes at about 55±5° C. The assembly was then cured resulting in the photo as shown in 16c.","As can be seen in FIG.","2, a very clear boundary of the two monomer mixtures was observed.","Example 2 In this experiment, a photochromic dye of Formula I, made by PPG Industries, was used.","5% photochromic dye was dissolved into a monomer mixture containing the components listed in Table 2, and 45% TPME as diluent.","For the clear monomer mixture, Monomer B monomer mixture that contained 55% TPME as diluent was used.","The viscosity of this material was ˜400 CP.","The monomer mixtures were then cured under 2% oxygen environment for 20 minutes, at 60° C. under 0.5 mW/cm2 intensity of Philips TL K 40 W/03 light bulbs.","The base curve mold was then removed and the lens stayed in the front curve mold.","The lens and front curve mold assembly was dropped into 90 C deionized water for 15 minutes to separate the lens from the mold, and extract and hydrate the lens.","The lens was then packaged in packaging solution in glass vials and sterilized at 121° C. The packing solution contains the following ingredients in deionized H2O: 0.18 weight % sodium borate [1330-43-4], Mallinckrodt; 0.91 weight % boric acid [10043-35-3], Mallinckrodt; 1.4 weight % sodium chloride, Sigma; 0.005 weight % methylether cellulose [232-674-9] from Fisher Scientific.","FIG.","3 shows the interferrograms of three exemplary lenses 30, 32, and 34 produced in this Example 2.The interferrograms display smooth and continuous interference lines across the junctions between the lens portions formed from the two monomer mixtures.","Accordingly, no obvious physical distortions were observed in any of the produced lenses.","Example 3 In this Example, the clear monomer outer region was Monomer mixture A, Table 1 and the pupil monomer mixture containing photochromic dye was based on Monomer mixture A with 5% additional PVP (poly(N-vinyl pyrolidone)) K90 added along with 6% photochromic dye.","The additional PVP K90 shifted the viscosity of Monomer mixture A from ˜300 CP to ˜1200 CP which was sufficient to maintain a centralized optic zone containing photochromic dye.","3 mg of the pupil monomer mixture was dosed into the center of a Zeonor front curve lens mold.","Next, 80 mg of monomer mixture A was dosed on top of the pupil monomer mixture.","A polypropylene base curve was then deposited on the front curve mold and the molds were closed.","The filled molds were irradiated using Philips TL 20 W/03T fluorescent bulbs above and below the lens molds and the following conditions: about 1 minute at about 1 mW/sec2 at ambient temperature, about 7 minutes at 2 mW/sec2 and 80° C. and about 4 minutes at 5.5.mW/sec2 and 80° C. All curing was done in N2.The molds were opened and lenses were extracted into a 70:30 (wt) solution of IPA and DI H2O at ambient temperature for at least 60 minutes.","The IPA:DI water solution was exchanged twice, and soaked in IPA:DI water at ambient temperature for at least about 30 minutes for each additional exchange to remove residual diluent and monomers, placed into deionized H2O for about 30 minutes, then equilibrated in borate buffered saline for at least about 24 hours and autoclaved at 122° C. for 30 minutes.","A lens 40 according to this experiment is shown at FIG.","4.One outcome of this experiment was that the addition of additional PVP K90 helped to shift the water content of the polymer in the pupil zone higher, thereby counterbalancing the reduction in water content caused by the addition of the hydrophobic photochromic dye.","Accordingly, the degree of hydration of the polymers formed from both the dye-containing monomer mixture and the clear monomer mixture were in substantially conformity.","Optical measurements indicate that the lenses created using this method have improved optic qualities.","Example 4 In this experiment, the clear monomer region was formed from Monomer B monomer mixture and the pupil region was formed from Monomer B material with photochromic dye.","However in this experiment the viscosity was adjusted by changing the concentration of the diluent component Monomer B monomer mixture to 45%.","The 45% diluent in the clear region is made up of 40% tert-amyl alcohol and 60% decanoic acid while the 45% diluent in the pupil monomer mixture was 100% decanoic acid.","By modifying the diluents in this experiment the centering of the photochromic pupil region was well contained within the central region of the optic zone.","Additional this change allowed the viscosities to differ by ˜1800cP between the inner (pupil) and outer (clear) regions while also providing a match in the swell of a hydrated lens in the two regions such that goods optics were obtained.","Example 5 A reaction mixture was formed from the components listed in Table 3 and diluent (D30) (77 wt % components: 23 wt % D30) (Reactive Mixture C).","Photochromic dye of Formula 1 (6 wt % based upon the weight of the reaction components of Reactive Mixture C) and an additional 5% PVP was dissolved into Reactive Mixture C to form a Dye Containing Reactive Mixture.","3 mg of the Dye Containing Reactive Mixture was dosed into the center of a Zeonor front curve lens mold.","Next, 80 mg of Reactive Mixture C was dosed on top of the Dye Containing Reactive Mixture.","A polypropylene base curve was then deposited and the molds were closed.","The filled molds were irradiated using Philips TL 20 W/03T fluorescent bulbs above and below the lens molds and the following conditions: about 1 minute at about 1 mW/sec2 at ambient temperature, about 7 minutes at 2 mW/sec2 and 80° C. and about 4 minutes at 5.5.mW/sec2 and 80° C. All curing was done in Na.","The molds were opened and lenses were extracted into a 70:30 (wt) solution of IPA and DI H2O at ambient temperature for at least 60 minutes.","The IPA:DI water solution was exchanged twice, and soaked in IPA:DI water at ambient temperature for at least about 30 minutes for each additional exchange to remove residual diluent and monomers, placed into deionized H2O for about 30 minutes, then equilibrated in borate buffered saline for at least about 24 hours and autoclaved at 122° C. for 30 minutes.","TABLE 3 Component SiGMA PVP (K90) 7 DMA 24 mPDMS 31 HEMA 6 Norbloc 2 CGI 1850 0.48 TEGDMA 1.5 Blue HEMA 0.02 Lenses of different powers were made.","The lenses with relatively thin center thicknesses (−1.00, 90 microns and −1.75, 120 microns) displayed smooth radii, good optics and comfort.","However, thicker lenses (>120 microns, −6.00 power) displayed lenses having a flattened top, with poor optics.","Examples 6-11 Photochromic dye of Formula II (6 wt % based upon the weight of the reaction components of reactive mixture) was dissolved into reactive mixtures shown in Table 4, to form dye containing reactive mixtures of Examples 6-11.D30 was added as a diluent in the amount listed in Table 4 (based upon the amount of reaction components and diluent.","TABLE 4 Ex # 6 7 8 9 10 11 DMA 24 23.89 23.77 23.77 23.6 23.45 TEGDMA 1 1 1 1 1 1 HEMA 9.55 9.55 9.55 9.55 9.55 9.55 mPDMS 12.5 12.5 12/5 12.5 12.5 12.5 SiMMA 36 36 36 36 36 36 Norbloc 1.7 1.7 1.7 1.7 1.7 1.7 Irgacure 0.25 0.36 0.48 0.48 0.65 0.8 819 PVP 15 15 15 15 15 15 % Diluent 29 29 29 35 35 35 3 mg of the dye containing reactive mixtures were dosed into the center of Zeonor front curve lens molds.","Next, 80 mg of Reactive Mixture 1 was dosed on top of the respective dye containing reactive mixture.","A polypropylene base curve was then deposited and the molds were closed.","The filled molds were irradiated using Philips TL 20 W/03T fluorescent bulbs (including UV filters within Zones 1 (A&B) and Zone 2A) above the lens molds at a constant 80° C. under the following conditions: about 7.5 minutes at about 2.2 mW/sec2(Zones 1 (A&B) and 2A)and about 7.5 minutes at 5.5 mW/sec2(Zones 2B and 3 (A&B)).","All curing was done in N2.The molds were opened and lenses were extracted into a 70:30 (wt) solution of IPA and DI H2O at ambient temperature for at least 60 minutes.","The IPA:DI water solution was exchanged twice, and soaked in IPA:DI water at ambient temperature for at least about 30 minutes for each additional exchange to remove residual diluent and monomers, placed into deionized H2O for about 30 minutes, then equilibrated in borate buffered saline for at least about 24 hours and autoclaved at 122° C. for 30 minutes.","The sagittal depth at the center was measured for lenses made in each example and compared to a calculated ideal or design sagittal depth using the following procedure.","A Nikon Scope SMZ1500 with component model numbers P-BERG (eye piece), P-IBSS (beam splitter camera port), DS-Fi1 (camera), P-FMD (mount), 1X WD 54 (lens), and base was used.","An LED Backlight was arranged adjacent to a water bath with a 45° mirror placed under a Nikon Scope 1X lens such that the light emitted from the LED Backlight illuminates through the water bath and onto the 45° mirror which reflects up into the scope.","See FIG.","9.The scope and the NIS Elements D were set to 0.75X.","The contact lens was placed into the water bath with the back curve side down.","The contact lens and scope were adjusted so that contact lens is in focus on the PC.","The lighting was adjusted such that back and front curve surfaces are visible.","Utilizing the Radius tool in the NIS Elements D Software three points along the back curve surface were selected on each side, such that a circumscribed circle was generated showing the “ideal” curvature of the back curve of the contact lens.","Utilizing the length tool the deviation of central photochromic region was determined by measuring the distance, at contact lens center, between the actual back curve surface of the contact lens and the “ideal” curvature.","Where visibility of the base curve surface in the central photochromic region was limited, a point representing the location of the back curve surface was created.","A point that represents the back curve surface can be generated by measuring from the front curve surface through the contact lens for a distance equal to the center thickness of the contact lens.","This set up was also used to photograph the lenses shown in FIGS.","5-8.The deviation from the ideal is listed in Table 5, below.","TABLE 5 Ex# [CGI 819] [diluent] Ave. dev.","(mm) 6 0.25 29% −0.109 7 0.36 29% −0.014 8 0.48 29% 0.057 9 0.48 36% −0.04 10 0.65 36% 0.0016 11 0.8 36% −0.0038 Example 12 and Comparative Examples 1 and 2 Lenses were made according to Example 6, using the dye monomer mixtures listed in Table 6.TABLE 6 Ex# 12 CE1 CE2 DMA 23.87 24 22.21 TEGDMA 1 1.25 1.5 HEMA 9.55 9.8 5.55 mPDMS 12.5 12 28 SiMMA 36 36 25.41 Norbloc 1.7 1.7 1.85 Irgacure 0.36 0.23 0 819 Irgacure 0 0 0.48 1850 Blue 0.02 0.02 0 HEMA PVP 15 15 15 % Diluent 31 27 27 Lenses made in each of Examples 12 and Comparative Examples 1 and 2 were photographed.","The images are shown at FIGS.","5-7.As can be seen from FIG.","5, the lens of Example 12 is well shaped and has a continuous curve across the entire lens surface.","The average percent deviation from the base curve for five lenses is −4.5%.","The lenses of Comparative Examples 1 and 2 (FIGS.","6 and 7, respectively) show flattened tops, which deviate undesirably from the design sagittal depth.","In FIG.","6, the design curve has been drawn in with a light white line, and the design sagittal height at the lens center is designated with a small white box.","Comparing FIGS.","6 and 7 with FIG.","5 (Example 6) shows the substantial improvement in hydrogel lens shape which can be achieved using the present invention.","The average deviation measured for Comparative Example 2 was −0.397 mm, which is more three times larger than the deviation displayed by the lenses in Example 6 (−0.109 mm).","Example 13 Lenses were made according to Example 6, but using the photochromic monomer mixture and clear monomer mixture listed in columns 2 and 3 of Table 7 below.","The photochromic monomer mixture contained 6 wt % photochromic compound of Formula II and 45 wt % decanoic acid as a diluents.","TABLE 7 Component PMM (wt %) CMM (wt %) Blue HEMA 0.02 0.02 DMA 18.9 18.9 Norbloc 2.2 2.2 OH—mPDMS 41.5 41.5 PVP K-90 12 12 TEGDMA 3 3 HEMA 22.13 22.13 CGI 819 0.25 0.25 Decanoic acid (diluent) 45 60% t-amyl 45 alcohol/40% decanoic acid FIG.","8 shows a photograph of a lens made according to Example 13.The lens is well shaped and the sagittal depth is within 100 microns of the design sagittal depth.","As stated prior, viscosity helps facilitate maintaining the photochromic within the central portion of a contact lens.","However, in order to adjusts the viscosity of the inner (photochromic pupil) and outer (clear) monomers of a contact lens it is important to adjust the two monomers in such a way that the hydrated swell of the final polymer(s) do not induce stress in the transitional region that occur between the photochromic and non photochromic regions.","The matching of the swell in the transitional region can be made through adjusting the levels or types of monomer components such as hydrophilic monomers including 2-hydroxyethyl methacrylate (HEMA), N,N-dimethyl acrylamide (DMA), N-vinyl pyrrolidone (NVP), N-methylacetamide, methacrylic acid, silicones, cross linker, polyvinyl pyrrolidone (PVP), polyacrylic acid (PAA), polymethylacetamide, polydimethyl acrylamide, PVA, and diluents.","The hydrogels of the present invention have water contents between about 20 and about 75% water.","In yet another embodiment the hydrogel contact lenses of the present invention have a water content of at least about 25%.","The lenses of the present invention may also have other desirable properties, including a tensile modulus of less than about 200 psi, in some embodiments less than about 150 psi and in other embodiments less than about 100 psi.","The lenses may further have oxygen permeabilities of greater than about 50 barrers, and in some embodiments greater than about 100 barrers.","It should be understood that combinations of the foregoing properties are desirable, and the above referenced ranges may be combined in any combination.","In some embodiments it may be desirable to have the properties of the photochromic and non-photochromic polymers substantially matched (within about 10%).","A contact lens monomer generally includes a reactive mixture which may be polymerized via exposure to actinic radiation.","Monomer A may generally include a monomer with reaction components and diluent (D30) as listed in Table 1 which can be mixed together with stirring or rolling for at least about 3 hours at about 23° C., until all components were dissolved.","The reactive components are reported as weight percent of all reactive components and the diluent is weight percent of final reaction mixture.","To form a lens, the reaction mixture may be placed into thermoplastic contact lens molds, and irradiated with actinic radiation such as, for example, with fluorescent bulbs at 45° C. for about 20 minutes in an N2 atmosphere.","The molds may be opened and lenses extracted into a 50:50 (wt) solution of IPA and H20, and soaked in IPA at ambient temperature for about 15 hours to remove residual diluent and monomers, placed into deionized H2O for about 30 minutes, then equilibrated in borate buffered saline for at least about 24 hours and autoclaved at 122° C. for 30 minutes.","While the principles of the invention have been described herein, it is to be understood by those skilled in the art that this description is made only by way of example and not as a limitation as to the scope of the invention.","Other embodiments are contemplated within the scope of the present invention in addition to the exemplary embodiments shown and described herein.","Modifications and substitutions by one of ordinary skill in the art are considered to be within the scope of the present invention, which is not to be limited except by the following claims."]],"string":"[\n [\n \"PUPIL-ONLY PHOTOCHROMIC CONTACT LENSES DISPLAYING DESIRABLE OPTICS AND COMFORT\",\n \"A method for making a hydrogel, photochromic contact lens including supplying a first lens composition comprising a contact lens monomer and a photochromic material to a front contact lens mold and supplying a second lens composition to said contact lens mold wherein the viscosity of said first composition is at least about 1000 cp greater than the viscosity of said second contact lens composition, and the makeup of said second composition matches the of said first composition to reduce strain between said compositions of the resulting lens.\"\n ],\n [\n \"1-9.\",\n \"(canceled) 10.A hydrogel contact lens comprising: a body with a front surface curve and a base surface curve wherein said front surface curve has a pupilary region and an outer region and said pupilary region is photochromic and concentric with said outer region wherein said hydrogel contact lens comprises a center sagittal depth within 100 microns of design sagittal depth.\",\n \"11.The contact lens of claim 10 wherein said pupilary region includes a pupil hydrogel composition and the outer region is formed from the reaction of a substantially clear monomer composition wherein the pupil hydrogel composition contains a photochromic dye and is formed from a reactive mixture having a higher viscosity which is at least about 1000 cp higher than the clear monomer composition.\",\n \"12.The contact lens of claim 10 wherein said pupilary region is about 9 mm or less in diameter.\",\n \"13.The contact lens of claim 10 wherein said pupilary region has a diameter of between about 4 and about 7 mm.\",\n \"14.The contact lens of claim 10 wherein said contact lens has a modulus of less than about 150 psi.\",\n \"15.The contact lens of claim 10 wherein said contact lens has a modulus of less than about 100 psi.\",\n \"16.The contact lens of claim 10 wherein said contact lens has an oxygen permeability of greater than about 50 barrers.\",\n \"17.The contact lens of claim 10 wherein said contact lens has an oxygen permeability of greater than about 100 barrers.\",\n \"18.The contact lens of claim 10 wherein said contact lens has a water content between about 20 and about 75%.\"\n ],\n [\n \" BACKGROUND INFORMATION Early contact lenses have been known with photochromic liquid held in a reservoir disposed between two materials forming a contact lens as part of a protective system against intense flashes such as a nuclear detonation.\",\n \"More recently, efforts have been directed towards photochromic contact lenses that can be worn daily and that quickly transition between colored and uncolored states utilizing photochromic dyes capable of absorbing light in specific wavelength ranges.\",\n \"In some examples, a dye is dispensed in a lens capable of exhibiting photochromism in the polymeric material comprising the contact lens so as to preferably have a single layer capable of absorbing light.\",\n \"However the contact lenses that exhibit photochromism throughout the entire lens area, “edge-to-edge”, are not desired due to cosmetic reasons.\",\n \"Therefore, efforts have been made to create a contact lens that changes color only in the central pupil region, “pupil-only” contact lens.\",\n \"US2003/0142267 discloses contact lenses having a photochromic material in the center or pupil region of the lens only.\",\n \"The lens is made by dispensing monomer mixes having different viscosities into the lens mold.\",\n \"The contact lenses are hard contact lenses which have no water content.\",\n \"The process disclosed in US2003/0142267 does not produce soft, hydrogel contact lenses which have desirable properties such as good optics and comfort.\",\n \"There is a need for an improved pupil only photochromic contact lens, including a method of manufacturing such lenses, that exhibits reduced deformation and optical distortion and increased comfort, wear ability, and cosmetic appearance.\"\n ],\n [\n \" BRIEF DESCRIPTION OF THE DRAWINGS The present invention is disclosed with reference to the accompanying drawings, wherein: FIGS.\",\n \"1A and 1B schematically represent methods of making pupil only photochromic lenses according to the invention.\",\n \"FIG.\",\n \"2 is an exemplary lens made according to the methods of the invention.\",\n \"FIG.\",\n \"3 shows an interferogram of a contact lens according to the invention.\",\n \"FIG.\",\n \"4 is an exemplary lens according to the invention.\",\n \"FIGS.\",\n \"5-8 are photographs of the lenses of Examples 12, Comparative Examples 1 and 2 and Example 13.FIG.\",\n \"9 is a schematic of the apparatus used to measure the deviation of sagittal depth from the design sagittal depth in the examples.\",\n \"detailed-description description=\\\"Detailed Description\\\" end=\\\"lead\\\"?\"\n ],\n [\n \"RELATED APPLICATIONS This application claims priority to provisional U.S. patent application Ser.\",\n \"No.\",\n \"61/323,410, filed Apr.\",\n \"13, 2010.TECHNICAL FIELD The present invention relates to contact lens eyewear and, more particularly, to contact lenses with photochromic dyes disposed in the region of the lens covering the pupil region when worn, the photochromic contact lenses having improved cosmetic appearance and improved structural qualities.\",\n \"The invention also relates to methods and materials used for making such photochromic contact lenses.\",\n \"BACKGROUND INFORMATION Early contact lenses have been known with photochromic liquid held in a reservoir disposed between two materials forming a contact lens as part of a protective system against intense flashes such as a nuclear detonation.\",\n \"More recently, efforts have been directed towards photochromic contact lenses that can be worn daily and that quickly transition between colored and uncolored states utilizing photochromic dyes capable of absorbing light in specific wavelength ranges.\",\n \"In some examples, a dye is dispensed in a lens capable of exhibiting photochromism in the polymeric material comprising the contact lens so as to preferably have a single layer capable of absorbing light.\",\n \"However the contact lenses that exhibit photochromism throughout the entire lens area, “edge-to-edge”, are not desired due to cosmetic reasons.\",\n \"Therefore, efforts have been made to create a contact lens that changes color only in the central pupil region, “pupil-only” contact lens.\",\n \"US2003/0142267 discloses contact lenses having a photochromic material in the center or pupil region of the lens only.\",\n \"The lens is made by dispensing monomer mixes having different viscosities into the lens mold.\",\n \"The contact lenses are hard contact lenses which have no water content.\",\n \"The process disclosed in US2003/0142267 does not produce soft, hydrogel contact lenses which have desirable properties such as good optics and comfort.\",\n \"There is a need for an improved pupil only photochromic contact lens, including a method of manufacturing such lenses, that exhibits reduced deformation and optical distortion and increased comfort, wear ability, and cosmetic appearance.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS The present invention is disclosed with reference to the accompanying drawings, wherein: FIGS.\",\n \"1A and 1B schematically represent methods of making pupil only photochromic lenses according to the invention.\",\n \"FIG.\",\n \"2 is an exemplary lens made according to the methods of the invention.\",\n \"FIG.\",\n \"3 shows an interferogram of a contact lens according to the invention.\",\n \"FIG.\",\n \"4 is an exemplary lens according to the invention.\",\n \"FIGS.\",\n \"5-8 are photographs of the lenses of Examples 12, Comparative Examples 1 and 2 and Example 13.FIG.\",\n \"9 is a schematic of the apparatus used to measure the deviation of sagittal depth from the design sagittal depth in the examples.\",\n \"DETAILED DESCRIPTION As used herein hydrogels are water swellable polymers which have water contents between about 20 and about 75% water.\",\n \"As used herein reactive mixture or monomer mixture means As used herein, expansion factor or swell is the change in dimension of a hydrogel article after hydration.\",\n \"Expansion factor may be calculated by dividing the diameter of hydrated lens by the lens formed in the mold prior to extraction and hydration and multiplying by 100.As used herein sagittal depth is the height of a contact lens, measured at its center (vertex) and from a chord drawn across the lens at its base diameter.\",\n \"Known tests may be used to measure sagittal depth, including ISO 18369-3, using an ultrasound instrument (section 4.1.4.2.3).\",\n \"Generally, one way to manufacture soft, hydrogel contact lenses is to cast mold contact lenses in plastic molds.\",\n \"Typically there are two mold portions which, when assembled, form a cavity.\",\n \"A reactive mixture which cures within the cavity forms a contact lens.\",\n \"Typically a first mold portion is dosed with the reactive mixture, and the second mold portion is placed on the first mold portion, and then the reactive mixture is cured.\",\n \"The reaction of the reactive mixture is commonly radiation activated.\",\n \"The reactive mixture in the cavity cures e.g.\",\n \"polymerizes and/or crosslinks to form the contact lens.\",\n \"The cured hydrogel contact lens is then removed from the molds and put in a solvent to remove the undesired chemical components.\",\n \"The lens normally swells in the process.\",\n \"The lens is then brought into contact with water to exchange the solvent with water, and give the hydrogel its final, stable shape and size.\",\n \"Specifically referring to FIG.\",\n \"1, two methods of manufacturing pupil only photochromic contact lenses are schematically shown.\",\n \"In the first method shown in FIG.\",\n \"1a, a front curve 11a is provided at step 10a.\",\n \"The front curve 11a is one part of the two part mold that is concave in shape so that the deposited material is held in the center of the mold by gravity.\",\n \"At step 12a, a small and precise dose of photochromic dye-containing monomer mixture 13a, or pupil monomer mixture, is supplied or dosed on a surface of the front curve mold 11a preferably in a substantially central location and in substantially circular configuration.\",\n \"In one embodiment, the photochromic dye-containing monomer mixture is dosed in a central circular area within the optic zone of the contact lens.\",\n \"The central circular area may be the same size as the optic zone, which in a typical contact lens is about 9 mm or less in diameter.\",\n \"In one embodiment, the central circular area has a diameter of between about 4 and about 7 mm and in another between about 4 and about 6 mm in diameter.\",\n \"Optionally, the photochromic dye-containing monomer mixture may be at least partially polymerized through a controlled curing mechanism at step 12a.\",\n \"Then, a dose of clear monomer mixture, which does not contain a photochromic dye, 15a is dosed on the top of the photochromic dye-containing monomer mixture 13a at step 14a.\",\n \"The dose of clear monomer mixture 15a fills the concave front curve 11a to the desired amount and then, at step 16a, the base curve 17a is provided and the mold halves 11a, 17a are put into their final curing position and the monomer mixtures are cured and/or polymerized completing the molding process.\",\n \"Where the polymerization process includes a photo-polymerization mechanism, the radiation, may be directed to either the front curve mold half or the base curve mold half, or both.\",\n \"The molded lens is then extracted to remove the un-desired chemical components and hydrated.\",\n \"An alternative method is shown in FIG.\",\n \"1b in which the first dose of photochromic monomer mixture 13b is provided in the center of a front curve mold 11b at step 12b and then an annular ring of clear monomer mixture 15b is dosed at the edge of the front curve mold 11b at step 14b.\",\n \"The resultant annular ring of clear monomeric material 15b is drawn to the center of the front curve by gravity.\",\n \"The base curve mold 17b is then supplied and the curing is initiated and completed at step 16b and the extraction and hydration step(s) (not shown) proceed to form the final hydrogel contact lens product.\",\n \"In order to provide a hydrogel contact lens with acceptable separation of the two regions (print quality) and low distortion, generally in terms of centralized photochromic dye 11 distribution, it has been found that, as described by US2003/0142267, increasing the viscosities of the monomer mixtures 13, 15 and, specifically, increasing the viscosity of the photochromic dye monomer mixture 13 as compared to the clear monomer mixture 15, reduces molecular diffusion of the monomers 13, 15 thereby maintaining photochromic dye in the central region.\",\n \"Using a photochromic dye monomer mixture that has higher viscosity than the clear monomer mixture helps to reduce the shear at the interface of the two monomers mixtures thereby reducing the physical mixing.\",\n \"An analysis of the Stokes-Einstein equation, shown below, illustrates the parameters that affect the diffusivity of a material: D = kT 6 πμ r where, D is the molecular diffusivity, k the Boltzmann constant, T the temperature, μ the viscosity and r the radius of the molecule.\",\n \"Operating at lower temperatures and using monomers of higher viscosities tends to reduce the molecular diffusion rate.\",\n \"In one embodiment the viscosity of the photochromic dye monomer mixture is at least about 1000 cp higher than the viscosity of the clear or peripheral monomer mixture and in another embodiment at least about 1500 cp higher.\",\n \"However, controlling the viscosity of the monomer mixtures as disclosed in US2003/0142267 was insufficient to provide hydrogel contact lenses having suitable optics and comfort.\",\n \"Hydrogel monomer mixtures when cured together produced contact lenses which displayed flattened optic zones, instead of lenses with a continuous radius.\",\n \"This may be measured by measuring the sagittal depth of the contact lens.\",\n \"Hydrogel lenses of the present invention have sagittal depths which are within about 100 microns of the design sagittal depth for the lens.\",\n \"In one embodiment the deviation from the design sagittal depth ranges from 0 (matched to the design sagittal depth) to −100 microns, which represents a slight flattening from the design sagittal depth.\",\n \"It has been found that by balancing the expansion factor of the polymers formed from the photochromic dye monomer mixture and the clear monomer mixture hydrogel contact lenses having desirable optics and comfort may be produced.\",\n \"In one embodiment the expansion factors of the polymers formed from the respective monomer mixtures are within about 10% in some embodiments within about 8% and in other embodiments within about 5%.\",\n \"The expansion factor may be adjusted by manipulating a number of formulation variables including the diluent concentration, the concentration and hydrophilicity or hydrophobicity of hydrophilic and hydrophobic components and concentration of initiator and crosslinker, and combinations thereof.\",\n \"Many photochromic dyes are highly hydrophobic and at the concentrations used in the present invention can have an impact on the expansion factor the hydrogels which contain them.\",\n \"In one embodiment, where the photochromic dye is hydrophobic, it is added to the formulation replacing a similar amount of another hydrophobic component.\",\n \"Similarly, if the photochromic compound were hydrophilic it will be added to the formulation replacing a similar amount of another hydrophilic component.\",\n \"In some embodiments, for example, where a silicone hydrogel contact lens is being produced, it may be desirable to maintain the concentration of the silicone components and replace a part of one of hydrophilic components.\",\n \"In these embodiments, multiple adjustments may be needed to achieve the desired expansion factor.\",\n \"In addition, other formulation variables may be modified to achieve the desired expansion factor.\",\n \"In some embodiments varying the concentration of the hydrophilic components, the diluent concentration and the initiator concentration, and combinations thereof have been effective at providing photochromic contact lenses having desirable optics and comfort.\",\n \"In one embodiment a hydrophilic polymer, such as poly(vinyl pyrrolidone) (PVP), methacrylic acid, polydimethylacrylamide or poly(vinyl methacetamide) may be added to the photochromic dye monomer mixture.\",\n \"In some embodiments it is desirable to use the same or similar components in both the photochromic dye and clear monomer mixtures.\",\n \"For example, it may be desirable to include the same hydrophilic components in both monomer mixtures.\",\n \"In this case, formulation variables in addition to the concentration of hydrophilic components may be varied.\",\n \"The examples further illustrate how the formulation variables may be balanced.\",\n \"In one embodiment, where a single sided cure is used the expansion factor is matched using monomers, diluent concentration and combinations thereof.\",\n \"Where cure is effected from only one side (such as during photocuring), increasing the initiator concentration may also be desirable.\",\n \"The clear monomer mixtures 15 that may be employed in the invention include soft contact lens materials made from HEMA based hydrogel or silicone hydrogel materials, which include but are not limited to silicone hydrogels, and fluorohydrogels.\",\n \"Examples of soft contact lenses formulations include but are not limited to the formulations of etafilcon A, genfilcon A, lenefilcon A, polymacon, acquafilcon A, balafilcon A, galyfilcon A, senofilcon, narafilcon A, narafilcon B, comfilcon, filcon II 3, asmofilcon, Monomer A and lotrafilcon A, and the like.\",\n \"Silicone hydrogels formulations, such as those disclosed in U.S. Pat.\",\n \"No.\",\n \"5,998,498; U.S. patent app.\",\n \"Ser.\",\n \"No.\",\n \"09/532,943, a continuation-in-part of U.S. patent app.\",\n \"Ser.\",\n \"No.\",\n \"09/532,943, filed on Aug. 30, 2000, and U.S. Pat.\",\n \"No.\",\n \"6,087,415, U.S. Pat.\",\n \"No.\",\n \"6,087,415, U.S. Pat.\",\n \"No.\",\n \"5,760,100, U.S. Pat.\",\n \"No.\",\n \"5,776,999, U.S. Pat.\",\n \"No.\",\n \"5,789,461, U.S. Pat.\",\n \"No.\",\n \"5,849,811, U.S. Pat.\",\n \"No.\",\n \"5,965,631, U.S. Pat.\",\n \"No.\",\n \"7,553,880, W02008/061992,US2010/048847, may also be used.\",\n \"These patents are hereby incorporated by reference for the hydrogel compositions contained therein.\",\n \"In one embodiment contact lens formulations are selected from etafilcon A, balafilcon A, acquafilcon A, lotrafilcon A, galyfilcon A, senfilcon, comfilcon, narafilcon, Monomer A and silicone hydrogels.\",\n \"Additionally, suitable contact lenses may be formed from reaction mixtures comprising at least one silicone containing component.\",\n \"A silicone-containing component is one that contains at least one [—Si—O—Si] group, in a monomer, macromer or prepolymer.\",\n \"Preferably, the Si and attached 0 are present in the silicone-containing component in an amount greater than 20 weight percent, and more preferably greater than 30 weight percent of the total molecular weight of the silicone-containing component.\",\n \"Useful silicone-containing components preferably comprise polymerizable functional groups such as acrylate, methacrylate, acrylamide, methacrylamide, N-vinyl lactam, N-vinylamide, and styryl functional groups.\",\n \"Examples of silicone components which may be included in the silicone hydrogel formulations include, but are not limited to silicone macromers, prepolymers and monomers.\",\n \"Examples of silicone macromers include, without limitation, polydimethylsiloxane methacrylated with pendant hydrophilic groups.\",\n \"Silicone and/or fluorine containing macromers may also be used.\",\n \"Suitable silicone monomers include tris(trimethylsiloxy)silylpropyl methacrylate, hydroxyl functional silicone containing monomers, such as 3-methacryloxy-2-hydroxypropyloxy)propylbis(trimethylsiloxy)methylsilane.. Additional suitable siloxane containing monomers include, amide analogs of TRIS.\",\n \"Vinylcarbanate or carbonate analogs, monomethacryloxypropyl terminated polydimethylsiloxanes, polydimethylsiloxanes, 3-methacryloxypropylbi s(trimethyl siloxy)methyl silane, methacryloxypropylpentamethyl disiloxane and combinations thereof.\",\n \"Exemplary photochromic materials that may be employed in some embodiments may include dyes mixed with contact lens materials, or alternately, polymerizeable monomers that are themselves photochromic.\",\n \"Other exemplary materials may include one or more of the following: polymerizable photochromic materials, such as polymerizable naphthoxazines; polymerizable spirobenzopyrans; polymerizable spirobenzopyrans and spirobenzothiopyrans; polymerizable fulgides; polymerizable naphthacenediones; polymerizable spirooxazines; polymerizable polyalkoxylated naphthopyrans; and polymerizable photochromic compounds.\",\n \"Furthermore the photochromic materials may include in some embodiments, one or more of the following classes of materials: chromenes, e.g., naphthopyrans, benzopyrans, indenonaphthopyrans and phenanthropyrans; spiropyrans, e.g., spiro(benzindoline)naphthopyrans, spiro(indoline)benzopyrans, spiro(indoline)naphthopyrans, spiro(indoline)quinopyrans and spiro(indoline)pyrans; oxazines, e.g., spiro(indoline)naphthoxazines, spiro(indoline)pyridobenzoxazines, spiro(benzindoline)pyridobenzoxazines, spiro(benzindoline)naphthoxazines and spiro(indoline)benzoxazines; mercury dithizonates, fulgides, fulgimides and mixtures of such photochromic compounds.\",\n \"Other photochromic materials that may be useful in the invention include organo-metal dithiozonates, i.e., (arylazo)-thioformic arylhydrazidates, e.g., mercury dithizonates; and fulgides and fulgimides, e.g., the 3-furyl and 3-thienyl fulgides and fulgimides.\",\n \"Non-limiting examples of suitable photochromic dyes include The following examples and experiments illustrate certain aspects of the present invention, but they do not delineate or limit the invention.\",\n \"EXAMPLES The following abbreviations are used in the examples below: Abbreviation Full Chemical Name SiGMA 2-propenoic acid, 2-methyl-,2-hydroxy-3-[3-[1,3,3,3- tetramethyl-1- [(trimethylsilyl)oxy]disiloxanyl]propoxy]propyl ester HEMA 2-hydroxyethyl methacrylate mPDMS 800-1000 MW (Mn) monomethacryloxypropyl terminated mono-n-butyl terminated polydimethylsiloxane DMA N,N-dimethylacrylamide PVP poly(N-vinyl pyrrolidone) (K value 90) Norbloc 2-(2′-hydroxy-5-methacrylyloxyethylphenyl)-2H- benzotriazole CGI 819 1:1 (wgt) blend of 1-hydroxycyclohexyl phenyl ketone and bis(2,6-dimethoxybenzoyl)-2,4-4-trimethylpentyl phosphine oxide Blue HEMA the reaction product of Reactive Blue 4 and HEMA IPA isopropyl alcohol D30 3,7-dimethyl-3-octanol mPDMS— mono-(3-methacryloxy-2-hydroxypropyloxy)propyl OH terminated, mono-butyl terminated polydimethylsiloxane (MW 1100) TEGDMA tetraethyleneglycol dimethacrylate TPME tripropylene glycol methyl ether Monomer Mixture A Monomer mixture A was formed from the components listed in Table 1 and diluent (D30) (77 wt % components:23 wt % D30).\",\n \"TABLE 1 Components Wt % SiGMA 28 PVP (K90) 7 DMA 24 mPDMS 31 HEMA 6 Norbloc 2 CGI 1850 0.48 TEGDMA 1.5 Blue HEMA 0.02 Monomer Mixture B Monomer mixture B was formed from the 55 wt % components listed in Table 1 and 45 wt % diluent (a mixture of 55 wt % TPME and 45 wt % decanoic acid co-diluent).\",\n \"TABLE 2 Monomer Components Monomers wt.\",\n \"% HO—mPDMS 55 TEGDMA 3 DMA 19.53 HEMA 8.00 PVP K-90 12 CGI 819 0.25 Norbloc 2.2 Blue HEMA 0.02 The Monomer mixture B formulations were degassed at about 600-700 mmHg for approximately 30 minutes at ambient temperature prior to dosing.\",\n \"Example 1 To demonstrate the feasibility for obtaining a pupil-only contact lens according to the method of FIG.\",\n \"1a, 20 mg ball-pen ink was mixed into 1 g Monomer B monomer mixture listed in Table 2 to simulate the dye-containing pupil monomer and 3 mg of this monomer mixture was dosed into the center of a front curve mold 10c.\",\n \"The viscosity of the monomer mixture was ˜3000 CP.\",\n \"Next, 80 mg of Monomer A monomer mixture was dosed on top of the pupil monomer mixture as shown in 14c.\",\n \"The viscosity of the Monomer A monomer mixture was ˜300 CP.\",\n \"A base curve was then deposited and the molds were closed and irradiated at 1.2 to 1.8 mW/cm2, under Philips TL K 40 W/03 light bulbs in a nitrogen atmosphere for 25 minutes at about 55±5° C. The assembly was then cured resulting in the photo as shown in 16c.\",\n \"As can be seen in FIG.\",\n \"2, a very clear boundary of the two monomer mixtures was observed.\",\n \"Example 2 In this experiment, a photochromic dye of Formula I, made by PPG Industries, was used.\",\n \"5% photochromic dye was dissolved into a monomer mixture containing the components listed in Table 2, and 45% TPME as diluent.\",\n \"For the clear monomer mixture, Monomer B monomer mixture that contained 55% TPME as diluent was used.\",\n \"The viscosity of this material was ˜400 CP.\",\n \"The monomer mixtures were then cured under 2% oxygen environment for 20 minutes, at 60° C. under 0.5 mW/cm2 intensity of Philips TL K 40 W/03 light bulbs.\",\n \"The base curve mold was then removed and the lens stayed in the front curve mold.\",\n \"The lens and front curve mold assembly was dropped into 90 C deionized water for 15 minutes to separate the lens from the mold, and extract and hydrate the lens.\",\n \"The lens was then packaged in packaging solution in glass vials and sterilized at 121° C. The packing solution contains the following ingredients in deionized H2O: 0.18 weight % sodium borate [1330-43-4], Mallinckrodt; 0.91 weight % boric acid [10043-35-3], Mallinckrodt; 1.4 weight % sodium chloride, Sigma; 0.005 weight % methylether cellulose [232-674-9] from Fisher Scientific.\",\n \"FIG.\",\n \"3 shows the interferrograms of three exemplary lenses 30, 32, and 34 produced in this Example 2.The interferrograms display smooth and continuous interference lines across the junctions between the lens portions formed from the two monomer mixtures.\",\n \"Accordingly, no obvious physical distortions were observed in any of the produced lenses.\",\n \"Example 3 In this Example, the clear monomer outer region was Monomer mixture A, Table 1 and the pupil monomer mixture containing photochromic dye was based on Monomer mixture A with 5% additional PVP (poly(N-vinyl pyrolidone)) K90 added along with 6% photochromic dye.\",\n \"The additional PVP K90 shifted the viscosity of Monomer mixture A from ˜300 CP to ˜1200 CP which was sufficient to maintain a centralized optic zone containing photochromic dye.\",\n \"3 mg of the pupil monomer mixture was dosed into the center of a Zeonor front curve lens mold.\",\n \"Next, 80 mg of monomer mixture A was dosed on top of the pupil monomer mixture.\",\n \"A polypropylene base curve was then deposited on the front curve mold and the molds were closed.\",\n \"The filled molds were irradiated using Philips TL 20 W/03T fluorescent bulbs above and below the lens molds and the following conditions: about 1 minute at about 1 mW/sec2 at ambient temperature, about 7 minutes at 2 mW/sec2 and 80° C. and about 4 minutes at 5.5.mW/sec2 and 80° C. All curing was done in N2.The molds were opened and lenses were extracted into a 70:30 (wt) solution of IPA and DI H2O at ambient temperature for at least 60 minutes.\",\n \"The IPA:DI water solution was exchanged twice, and soaked in IPA:DI water at ambient temperature for at least about 30 minutes for each additional exchange to remove residual diluent and monomers, placed into deionized H2O for about 30 minutes, then equilibrated in borate buffered saline for at least about 24 hours and autoclaved at 122° C. for 30 minutes.\",\n \"A lens 40 according to this experiment is shown at FIG.\",\n \"4.One outcome of this experiment was that the addition of additional PVP K90 helped to shift the water content of the polymer in the pupil zone higher, thereby counterbalancing the reduction in water content caused by the addition of the hydrophobic photochromic dye.\",\n \"Accordingly, the degree of hydration of the polymers formed from both the dye-containing monomer mixture and the clear monomer mixture were in substantially conformity.\",\n \"Optical measurements indicate that the lenses created using this method have improved optic qualities.\",\n \"Example 4 In this experiment, the clear monomer region was formed from Monomer B monomer mixture and the pupil region was formed from Monomer B material with photochromic dye.\",\n \"However in this experiment the viscosity was adjusted by changing the concentration of the diluent component Monomer B monomer mixture to 45%.\",\n \"The 45% diluent in the clear region is made up of 40% tert-amyl alcohol and 60% decanoic acid while the 45% diluent in the pupil monomer mixture was 100% decanoic acid.\",\n \"By modifying the diluents in this experiment the centering of the photochromic pupil region was well contained within the central region of the optic zone.\",\n \"Additional this change allowed the viscosities to differ by ˜1800cP between the inner (pupil) and outer (clear) regions while also providing a match in the swell of a hydrated lens in the two regions such that goods optics were obtained.\",\n \"Example 5 A reaction mixture was formed from the components listed in Table 3 and diluent (D30) (77 wt % components: 23 wt % D30) (Reactive Mixture C).\",\n \"Photochromic dye of Formula 1 (6 wt % based upon the weight of the reaction components of Reactive Mixture C) and an additional 5% PVP was dissolved into Reactive Mixture C to form a Dye Containing Reactive Mixture.\",\n \"3 mg of the Dye Containing Reactive Mixture was dosed into the center of a Zeonor front curve lens mold.\",\n \"Next, 80 mg of Reactive Mixture C was dosed on top of the Dye Containing Reactive Mixture.\",\n \"A polypropylene base curve was then deposited and the molds were closed.\",\n \"The filled molds were irradiated using Philips TL 20 W/03T fluorescent bulbs above and below the lens molds and the following conditions: about 1 minute at about 1 mW/sec2 at ambient temperature, about 7 minutes at 2 mW/sec2 and 80° C. and about 4 minutes at 5.5.mW/sec2 and 80° C. All curing was done in Na.\",\n \"The molds were opened and lenses were extracted into a 70:30 (wt) solution of IPA and DI H2O at ambient temperature for at least 60 minutes.\",\n \"The IPA:DI water solution was exchanged twice, and soaked in IPA:DI water at ambient temperature for at least about 30 minutes for each additional exchange to remove residual diluent and monomers, placed into deionized H2O for about 30 minutes, then equilibrated in borate buffered saline for at least about 24 hours and autoclaved at 122° C. for 30 minutes.\",\n \"TABLE 3 Component SiGMA PVP (K90) 7 DMA 24 mPDMS 31 HEMA 6 Norbloc 2 CGI 1850 0.48 TEGDMA 1.5 Blue HEMA 0.02 Lenses of different powers were made.\",\n \"The lenses with relatively thin center thicknesses (−1.00, 90 microns and −1.75, 120 microns) displayed smooth radii, good optics and comfort.\",\n \"However, thicker lenses (>120 microns, −6.00 power) displayed lenses having a flattened top, with poor optics.\",\n \"Examples 6-11 Photochromic dye of Formula II (6 wt % based upon the weight of the reaction components of reactive mixture) was dissolved into reactive mixtures shown in Table 4, to form dye containing reactive mixtures of Examples 6-11.D30 was added as a diluent in the amount listed in Table 4 (based upon the amount of reaction components and diluent.\",\n \"TABLE 4 Ex # 6 7 8 9 10 11 DMA 24 23.89 23.77 23.77 23.6 23.45 TEGDMA 1 1 1 1 1 1 HEMA 9.55 9.55 9.55 9.55 9.55 9.55 mPDMS 12.5 12.5 12/5 12.5 12.5 12.5 SiMMA 36 36 36 36 36 36 Norbloc 1.7 1.7 1.7 1.7 1.7 1.7 Irgacure 0.25 0.36 0.48 0.48 0.65 0.8 819 PVP 15 15 15 15 15 15 % Diluent 29 29 29 35 35 35 3 mg of the dye containing reactive mixtures were dosed into the center of Zeonor front curve lens molds.\",\n \"Next, 80 mg of Reactive Mixture 1 was dosed on top of the respective dye containing reactive mixture.\",\n \"A polypropylene base curve was then deposited and the molds were closed.\",\n \"The filled molds were irradiated using Philips TL 20 W/03T fluorescent bulbs (including UV filters within Zones 1 (A&B) and Zone 2A) above the lens molds at a constant 80° C. under the following conditions: about 7.5 minutes at about 2.2 mW/sec2(Zones 1 (A&B) and 2A)and about 7.5 minutes at 5.5 mW/sec2(Zones 2B and 3 (A&B)).\",\n \"All curing was done in N2.The molds were opened and lenses were extracted into a 70:30 (wt) solution of IPA and DI H2O at ambient temperature for at least 60 minutes.\",\n \"The IPA:DI water solution was exchanged twice, and soaked in IPA:DI water at ambient temperature for at least about 30 minutes for each additional exchange to remove residual diluent and monomers, placed into deionized H2O for about 30 minutes, then equilibrated in borate buffered saline for at least about 24 hours and autoclaved at 122° C. for 30 minutes.\",\n \"The sagittal depth at the center was measured for lenses made in each example and compared to a calculated ideal or design sagittal depth using the following procedure.\",\n \"A Nikon Scope SMZ1500 with component model numbers P-BERG (eye piece), P-IBSS (beam splitter camera port), DS-Fi1 (camera), P-FMD (mount), 1X WD 54 (lens), and base was used.\",\n \"An LED Backlight was arranged adjacent to a water bath with a 45° mirror placed under a Nikon Scope 1X lens such that the light emitted from the LED Backlight illuminates through the water bath and onto the 45° mirror which reflects up into the scope.\",\n \"See FIG.\",\n \"9.The scope and the NIS Elements D were set to 0.75X.\",\n \"The contact lens was placed into the water bath with the back curve side down.\",\n \"The contact lens and scope were adjusted so that contact lens is in focus on the PC.\",\n \"The lighting was adjusted such that back and front curve surfaces are visible.\",\n \"Utilizing the Radius tool in the NIS Elements D Software three points along the back curve surface were selected on each side, such that a circumscribed circle was generated showing the “ideal” curvature of the back curve of the contact lens.\",\n \"Utilizing the length tool the deviation of central photochromic region was determined by measuring the distance, at contact lens center, between the actual back curve surface of the contact lens and the “ideal” curvature.\",\n \"Where visibility of the base curve surface in the central photochromic region was limited, a point representing the location of the back curve surface was created.\",\n \"A point that represents the back curve surface can be generated by measuring from the front curve surface through the contact lens for a distance equal to the center thickness of the contact lens.\",\n \"This set up was also used to photograph the lenses shown in FIGS.\",\n \"5-8.The deviation from the ideal is listed in Table 5, below.\",\n \"TABLE 5 Ex# [CGI 819] [diluent] Ave. dev.\",\n \"(mm) 6 0.25 29% −0.109 7 0.36 29% −0.014 8 0.48 29% 0.057 9 0.48 36% −0.04 10 0.65 36% 0.0016 11 0.8 36% −0.0038 Example 12 and Comparative Examples 1 and 2 Lenses were made according to Example 6, using the dye monomer mixtures listed in Table 6.TABLE 6 Ex# 12 CE1 CE2 DMA 23.87 24 22.21 TEGDMA 1 1.25 1.5 HEMA 9.55 9.8 5.55 mPDMS 12.5 12 28 SiMMA 36 36 25.41 Norbloc 1.7 1.7 1.85 Irgacure 0.36 0.23 0 819 Irgacure 0 0 0.48 1850 Blue 0.02 0.02 0 HEMA PVP 15 15 15 % Diluent 31 27 27 Lenses made in each of Examples 12 and Comparative Examples 1 and 2 were photographed.\",\n \"The images are shown at FIGS.\",\n \"5-7.As can be seen from FIG.\",\n \"5, the lens of Example 12 is well shaped and has a continuous curve across the entire lens surface.\",\n \"The average percent deviation from the base curve for five lenses is −4.5%.\",\n \"The lenses of Comparative Examples 1 and 2 (FIGS.\",\n \"6 and 7, respectively) show flattened tops, which deviate undesirably from the design sagittal depth.\",\n \"In FIG.\",\n \"6, the design curve has been drawn in with a light white line, and the design sagittal height at the lens center is designated with a small white box.\",\n \"Comparing FIGS.\",\n \"6 and 7 with FIG.\",\n \"5 (Example 6) shows the substantial improvement in hydrogel lens shape which can be achieved using the present invention.\",\n \"The average deviation measured for Comparative Example 2 was −0.397 mm, which is more three times larger than the deviation displayed by the lenses in Example 6 (−0.109 mm).\",\n \"Example 13 Lenses were made according to Example 6, but using the photochromic monomer mixture and clear monomer mixture listed in columns 2 and 3 of Table 7 below.\",\n \"The photochromic monomer mixture contained 6 wt % photochromic compound of Formula II and 45 wt % decanoic acid as a diluents.\",\n \"TABLE 7 Component PMM (wt %) CMM (wt %) Blue HEMA 0.02 0.02 DMA 18.9 18.9 Norbloc 2.2 2.2 OH—mPDMS 41.5 41.5 PVP K-90 12 12 TEGDMA 3 3 HEMA 22.13 22.13 CGI 819 0.25 0.25 Decanoic acid (diluent) 45 60% t-amyl 45 alcohol/40% decanoic acid FIG.\",\n \"8 shows a photograph of a lens made according to Example 13.The lens is well shaped and the sagittal depth is within 100 microns of the design sagittal depth.\",\n \"As stated prior, viscosity helps facilitate maintaining the photochromic within the central portion of a contact lens.\",\n \"However, in order to adjusts the viscosity of the inner (photochromic pupil) and outer (clear) monomers of a contact lens it is important to adjust the two monomers in such a way that the hydrated swell of the final polymer(s) do not induce stress in the transitional region that occur between the photochromic and non photochromic regions.\",\n \"The matching of the swell in the transitional region can be made through adjusting the levels or types of monomer components such as hydrophilic monomers including 2-hydroxyethyl methacrylate (HEMA), N,N-dimethyl acrylamide (DMA), N-vinyl pyrrolidone (NVP), N-methylacetamide, methacrylic acid, silicones, cross linker, polyvinyl pyrrolidone (PVP), polyacrylic acid (PAA), polymethylacetamide, polydimethyl acrylamide, PVA, and diluents.\",\n \"The hydrogels of the present invention have water contents between about 20 and about 75% water.\",\n \"In yet another embodiment the hydrogel contact lenses of the present invention have a water content of at least about 25%.\",\n \"The lenses of the present invention may also have other desirable properties, including a tensile modulus of less than about 200 psi, in some embodiments less than about 150 psi and in other embodiments less than about 100 psi.\",\n \"The lenses may further have oxygen permeabilities of greater than about 50 barrers, and in some embodiments greater than about 100 barrers.\",\n \"It should be understood that combinations of the foregoing properties are desirable, and the above referenced ranges may be combined in any combination.\",\n \"In some embodiments it may be desirable to have the properties of the photochromic and non-photochromic polymers substantially matched (within about 10%).\",\n \"A contact lens monomer generally includes a reactive mixture which may be polymerized via exposure to actinic radiation.\",\n \"Monomer A may generally include a monomer with reaction components and diluent (D30) as listed in Table 1 which can be mixed together with stirring or rolling for at least about 3 hours at about 23° C., until all components were dissolved.\",\n \"The reactive components are reported as weight percent of all reactive components and the diluent is weight percent of final reaction mixture.\",\n \"To form a lens, the reaction mixture may be placed into thermoplastic contact lens molds, and irradiated with actinic radiation such as, for example, with fluorescent bulbs at 45° C. for about 20 minutes in an N2 atmosphere.\",\n \"The molds may be opened and lenses extracted into a 50:50 (wt) solution of IPA and H20, and soaked in IPA at ambient temperature for about 15 hours to remove residual diluent and monomers, placed into deionized H2O for about 30 minutes, then equilibrated in borate buffered saline for at least about 24 hours and autoclaved at 122° C. for 30 minutes.\",\n \"While the principles of the invention have been described herein, it is to be understood by those skilled in the art that this description is made only by way of example and not as a limitation as to the scope of the invention.\",\n \"Other embodiments are contemplated within the scope of the present invention in addition to the exemplary embodiments shown and described herein.\",\n \"Modifications and substitutions by one of ordinary skill in the art are considered to be within the scope of the present invention, which is not to be limited except by the following claims.\"\n ]\n]"},"source":{"kind":"string","value":"Patent_15872008"}}},{"rowIdx":4493982,"cells":{"text":{"kind":"list like","value":[["AGGREGATING CONTENT FROM DIFFERENT CONTENT SOURCES AT A CLOUD SERVICE","A cloud service stores and aggregates content that is obtained from different content sources using different protocols.","For example, the content may include electronic messages, calendar information, contacts, social network content, feed data, search results, and the like.","The cloud service aggregates content for each user based on the user's configuration settings.","The cloud service may perform processing on the aggregated content before it is delivered and displayed to the user on the client device.","For example, one or more views may be generated and stored by the cloud service before the view is requested from the client.","Changes made to the aggregated content on the client may be synchronized with the content source.","Searches may be made across all or a portion of the different content sources that are aggregated for a user."],["1.A method for aggregating content at a cloud service, comprising: obtaining content from different content sources that use different protocols using the cloud service; aggregating the content at the cloud service and associating the aggregated content with a user; storing the aggregated content for the user at the cloud service; and using a single delivery protocol to deliver aggregated content to a client computing device regardless of the different protocols used by the cloud service to obtain the content.","2.The method of claim 1, wherein obtaining the content from the different content sources that use the different protocols comprises obtaining electronic messages, calendar information, and contact information associated with the user.","3.The method of claim 1, wherein obtaining the content from the different content sources that use the different protocols comprises obtaining at least one of: social network content obtained from a social network; search results obtained from a search engine; or feed content.","4.The method of claim 1, further comprising generating different views of the aggregated content at the cloud service and storing the different views at the cloud service.","5.The method of claim 1, wherein storing the aggregated content for the user at the cloud service comprises storing each different content source as separate content within a data storage.","6.The method of claim 1, further comprising determining when a change is made to the aggregated content and synchronizing the change back to the content source where the content was obtained.","7.The method of claim 1, further comprising obtaining provider specific information from at least one of the content sources in addition to using a synchronization protocol specified by the provider of the content source.","8.The method of claim 1, further comprising receiving a search query from a client device and performing a search across at least a portion of the different content sources aggregated for the user.","9.The method of claim 1, further comprising receiving a search query from a client device and performing a search using the search query across different mail sources to locate messages from different mail providers.","10.A computer-readable medium storing computer-executable instructions for aggregating content at a cloud service, comprising: obtaining content from different content sources using the cloud service including electronic message content, calendar content, and contact content that use different protocols; aggregating the content at the cloud service and associating the aggregated content with a user; storing the aggregated content for the user at the cloud service; and using a single delivery protocol to deliver aggregated content to a client computing device regardless of the different protocols used by the cloud service to obtain the content.","11.The computer-readable medium of claim 10, further comprising generating different views of the aggregated content at the cloud service and storing the different views at the cloud service.","12.The computer-readable medium of claim 10, wherein storing the aggregated content for the user at the cloud service comprises storing each different content source as separate content within a data storage.","13.The computer-readable medium of claim 10, further comprising determining when a change is made to the aggregated content and synchronizing the change back to the content source where the content was obtained.","14.The computer-readable medium of claim 10, further comprising obtaining provider specific information from at least one of the content sources in addition to using a synchronization protocol specified by the provider of the content source.","15.The computer-readable medium of claim 10, further comprising receiving a search query from a client device and performing a search across at least a portion of the different content sources aggregated for the user.","16.The computer-readable medium of claim 10, further comprising receiving a search query from a client device and performing a search using the search query across different mail sources to locate messages from different mail providers.","17.A system for aggregating content at a cloud service, comprising: a processor and memory; an operating environment executing using the processor; and an content manager that is configured to perform actions comprising: obtaining content from different content sources using the cloud service including electronic message content, calendar content, and contact content that use different protocols; aggregating the content at the cloud service and associating the aggregated content with a user; storing the aggregated content for the user at the cloud service; generating different views of the aggregated content at the cloud service; and using a single delivery protocol to deliver one of the views to a client computing device.","18.The system of claim 17, wherein storing the aggregated content for the user at the cloud service comprises storing each different content source as separate content within a data storage.","19.The system of claim 17, further comprising determining when a change is made to the aggregated content and synchronizing the change back to the content source where the content was obtained.","20.The system of claim 17, further comprising obtaining provider specific information from at least one of the content sources in addition to using a synchronization protocol specified by the provider of the content source."],[" BACKGROUND Personal Information Manager (PIM) applications are commonly used by computer users.","PIM applications are used for recording, tracking, and managing personal information for a user.","For example, a user may use a PIM application to access email, contacts and calendar information from one or more providers.","The content that is used by the PIM application may be obtained from a variety of different content sources."],[" SUMMARY This Summary is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description.","This Summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.","A cloud service stores and aggregates content that is obtained from different content sources using different protocols.","For example, the content may include electronic messages, calendar information, contacts, social network content, feed data, search results, and the like.","The cloud service aggregates content for a user based on the user's configuration settings.","For example, a user may configure their personal information manager (PIM) application to include mail from different mail providers.","The user may also configure their PIM application to include contacts from a social network, as well as calendar events from one or more calendars or content sources.","Instead of the client PIM application accessing each of the individual content sources and incorporating the content into the PIM application, the cloud service obtains and aggregates the content obtained from the different content sources.","The cloud service may perform processing on the aggregated content before it is delivered and displayed to the user on the client device.","For example, one or more views may be generated and stored by the cloud service before the view is requested from the client.","Changes made to the aggregated content on the client may be synchronized with the content source.","For example, in response to a user making a change to an email that is associated with a different email provider, the change is synchronized with the different email provider.","Searches may be made across all or a portion of the different content sources that are aggregated for a user.","For example, a user may view the messages from a particular user regardless of the message provider providing the content to the user.","Similarly, a user may perform a general search across each of the different content sources to locate items matching a search query."],["CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of, and claims priority to, non-provisional U.S. application Ser.","No.","13/925,599, filed Jun.","24, 2013, which application is incorporated herein by reference in their entirety.","BACKGROUND Personal Information Manager (PIM) applications are commonly used by computer users.","PIM applications are used for recording, tracking, and managing personal information for a user.","For example, a user may use a PIM application to access email, contacts and calendar information from one or more providers.","The content that is used by the PIM application may be obtained from a variety of different content sources.","SUMMARY This Summary is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description.","This Summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.","A cloud service stores and aggregates content that is obtained from different content sources using different protocols.","For example, the content may include electronic messages, calendar information, contacts, social network content, feed data, search results, and the like.","The cloud service aggregates content for a user based on the user's configuration settings.","For example, a user may configure their personal information manager (PIM) application to include mail from different mail providers.","The user may also configure their PIM application to include contacts from a social network, as well as calendar events from one or more calendars or content sources.","Instead of the client PIM application accessing each of the individual content sources and incorporating the content into the PIM application, the cloud service obtains and aggregates the content obtained from the different content sources.","The cloud service may perform processing on the aggregated content before it is delivered and displayed to the user on the client device.","For example, one or more views may be generated and stored by the cloud service before the view is requested from the client.","Changes made to the aggregated content on the client may be synchronized with the content source.","For example, in response to a user making a change to an email that is associated with a different email provider, the change is synchronized with the different email provider.","Searches may be made across all or a portion of the different content sources that are aggregated for a user.","For example, a user may view the messages from a particular user regardless of the message provider providing the content to the user.","Similarly, a user may perform a general search across each of the different content sources to locate items matching a search query.","BRIEF DESCRIPTION OF THE DRAWINGS FIG.","1 shows a system including a cloud service that aggregates content for different users that is obtained from different content sources; FIG.","2 illustrates a synchronization engine included in a cloud service that augments content that is obtained from different content sources; FIG.","3 illustrates a user accessing a cloud service and performing a search across the aggregated content obtained from different content sources; FIG.","4 shows a process of a cloud service aggregating content from different content sources; FIG.","5 shows a process of a client interacting with a cloud service that stores aggregated content for the client; FIG.","6 illustrates an exemplary online system for aggregating content from different content sources; and FIGS.","7, 8A, 8B, and 9 and the associated descriptions provide a discussion of a variety of operating environments in which embodiments of the invention may be practiced.","DETAILED DESCRIPTION Referring now to the drawings, in which like numerals represent like elements, various embodiments will be described.","FIG.","1 shows a system including a cloud service that aggregates content for different users that is obtained from different content sources.","As illustrated, system 100 includes application(s) 110, content sources 120, search 130, cloud service 105, aggregated content 135, content manager 26, other remote clients 140, and computing device 150.Content manager 26 is configured to aggregate content that is obtained from different content sources.","According to an embodiment, the content is aggregated by the Cloud (e.g.","“online”) service 105 and is stored by the cloud service 105.For example, the aggregated content may be stored in a data store (e.g.","aggregated content 135).","The content sources 120 that are aggregated may include many different types of content.","For example, the content sources may include content relating to electronic messages, calendars (public, private), contacts, social network content, feed data, search results, and the like.","Using content manager 26, cloud service 105 aggregates content for different users based on the configuration settings that are associated with a user.","For example, a user may configure their personal information manager (PIM) application to include mail, contacts, and calendars from different service providers.","The user may also configure their PIM application to include contacts from a social network, as well as calendar events from one or more content sources.","Instead of a client PIM application accessing each of the individual content providers and storing the content, cloud service 105 obtains and aggregates the content that is obtained from the different content sources for the user.","According to an embodiment, service 105 stores each user's data that is obtained from each content source separately.","According to an embodiment, content manager 26 may be configured to augment the aggregated content 135 to include additional content.","For example, calendar events may be augmented to include: traffic information, driving directions, news information, weather information, related events, and the like.","Generally, the content is augmented to include additional information relating to the content.","Cloud service 105 may augment the aggregated content differently based on the type of the content being augmented.","For example, electronic messages may be augmented differently as compared to when augmenting calendar events or contact cards.","As illustrated in FIG.","1, computing device 150 shows Calendar 155 that displays a weekly view of a calendar that includes different events that may be obtained from different content sources.","In the current example, augmented content is shown on April 16th.","The augmented content and the aggregated content may include content from different content sources.","For example, the content may include traffic information, driving directions, location information ,restaurant information, social network posts, news feeds, calendar content, mail content, and the like.","Changes made to the aggregated content on the client may be synchronized with the external content source.","For example, in response to a user making a change to an email that is associated with a different email provider, content manager 26 synchronizes the change with the content stored by the different email provider.","Cloud service 105 may perform processing on the aggregated content before it is displayed or delivered to the user on a client computing device.","For example, one or more views may be generated by content manager 26 and stored by the cloud service 105 before the view is requested from the client computing device.","In order to facilitate communication with content manager 26, one or more callback routines, may be implemented.","Application(s) 110 may be a variety of applications, such as PIM applications, business productivity applications, entertainment applications, music applications, travel applications, video applications, and the like.","Generally, application(s) 110 may be any application that includes content that may be aggregated.","The application(s) 110 may be configured to receive different types of input (e.g.","speech input, touch input, keyboard input (e.g.","a physical keyboard and/or Software Input Panel (SIP)) and/or other types of input.","System 100 as illustrated comprises one or more touch screen input devices, such as computing device 150, that detects when a touch input has been received (e.g.","a finger touching or nearly touching the touch screen).","Any type of touch screen may be utilized that detects a user's touch input.","For example, the touch screen may include one or more layers of capacitive material that detects the touch input.","More details are provided below.","FIG.","2 illustrates a synchronization engine included in a cloud service that augments content that is obtained from different content sources.","As illustrated, system 200 includes content sources 120, synchronization engine 220, content manager 26 including aggregator 250 and augmenter 260, data store 230, cloud service 105, client 270, and other clients 275.Instead of a client application connecting with each different content provider to obtain content, service 105 using content manager 26 obtains and aggregates content from content sources 120.According to an embodiment, a client (e.g.","client 270) may use a single protocol to communicate with the different content obtained by cloud service 105.As discussed above, content sources 120 may include many different content sources.","For example, content sources 120 may include: feed sources; Personal Information Management (PIM) sources (e.g.","OUTLOOK, GMAIL, YAHOO) that include content relating to electronic messages, calendars, tasks, and the like; social network sources (e.g.","TWITTER, FACEBOOK, LINKEDIN .",".",".","); weather sources; entertainment sources; map and navigation sources; public calendar sources, private calendar sources, and the like.","Generally, a content source may be any source from which content may be obtained from and aggregated for a user.","Each client (user) may determine what content they would like aggregated.","For example, when a user first accesses cloud service 105, they may configure what content sources they would like to include (e.g.","mail from GMAIL and YAHOO, as well as OUTLOOK email).","The user may also select social network sources (e.g.","YAMMER, SHAREPOINT, FACEBOOK, TWITTER, .",".",".","), feeds, and the like.","For example, the use may select to include contacts and contact info, FACEBOOK, GMAIL, TWITTER, LINKEDIN, and the like.","In response to the user selections of the content sources, content manager 26 uses aggregator 250 to obtain the content from the content source.","The retrieved content is stored in the cloud service 105 in data store 230.According to an embodiment, each content source that is selected by a user to be aggregated is stored separately within data store 230.In other words, the content from one content source is not mixed with content from another content source.","According to another embodiment, the content sources may be stored mixed within data store 230.Aggregator 250 may obtain content from the content sources in response to different events.","For example, aggregator 250 may obtain content periodically, in response to a notification, or in response to some other event.","Synchronization engine 220 is configured to act an interface between the cloud service 105 and the content sources.","Different content sources may use different protocols 216 to allow access to content in a content source.","For example, the Internet Message Access Protocol (IMAP) is a generic protocol for email that may be used by one or more content sources.","Other common protocols include Exchange Web Service (EWS), Messaging Application Programming Interface (MAPI), Exchange Active Sync (EAS), Post Office Protocol (POP), Simple Mail Transfer Protocol (SMTP), as well as many other protocols that may be associated with accessing and interacting with content in a content source.","Some content sources may use their own defined protocol or may modify a common protocol.","Synchronization engine 220 interacts with each content source using the protocol that is associated with the content source being accessed.","Synchronization engine 220 is configured to aggregate provider specific content.","Instead of just using a generic protocol (e.g.","IMAP, MAPI, .",".",". )","to obtain content from each content source, specific provider synchronization interfaces 218 may be created and used to obtain additional content and information from the content source.","For example, the provider specific interfaces 218 may obtain information form the provider for one or more provider specific features.","For example, a provider specific interface to the GMAIL service may obtain labels in GMAIL and map that information to the same feature or another feature used when a client accesses the GMAIL content (e.g.","map label in GMAIL to a mail folder).","According to another embodiment, the provider synchronization interfaces 218 may be configured to maintain the use of provider specific features.","Generally, the provider specific interfaces 218 are configured to access features of a content provider that are not available using a common protocol that is associated with the service provider.","For example, while mail may be obtained from a mail service provider using a protocol, the defined protocol may not provide functionality to interface with all of the different features that are provided by the service provider.","According to an embodiment, synchronization engine 220 is configured to allow two-way synchronization between the different content sources and data store 230 in the cloud service.","For example, a user (e.g.","client 270) may make a change to an email that was obtained from a different mail service provider that is synchronized back to the different service provider.","This is different from traditional applications that download the content to an application but do not synchronize changes back to the service after a change is made.","As another example, a user may add a folder in the client that translates in mapping the folder to a label.","The provider synchronization interface logic is specific logic that applies to each content provider.","Content may be synchronized to different fidelity levels.","The aggregated content for a user may be augmented with additional content using augmenter 260.The content may be augmented in response to an item being created (e.g.","an appointment, a message) and/or augmented at some other time.","For example, the content may be aggregated when the user opens a view of the content.","The following examples of augmenting content are examples, and are not intended to be limiting.","A view of a user's calendar may be augmented using public calendar feeds.","For example, the calendar feeds could be sports calendars, school calendars, social experiences, home schedules, and the like.","Information relating to the calendar may also be obtained from other sources.","A search may automatically be performed to locate content that is referenced in a message, in a calendar, in a task, and the like.","For example, when viewing the calendar that includes a schedule of games, the scores of the games may automatically be added to the view after performing a search for the score.","Instead of each client having to obtain the content directly from the content sources using the different protocols and storing the aggregated information on the client computing device, the cloud service 105 stores the content, performs the aggregation, and delivers aggregated content to a client using a single communication channel (a single delivery protocol).","Client 270 interacts with the cloud service 105 using a single protocol even though cloud service used many different protocols to obtain the aggregated content.","According to an embodiment, client 270 is a thin and portable client (e.g.","it does not need to include the synchronization logic, protocols and other functionality that cloud service 105 includes).","Other clients 275 also communicate with cloud service 105 to access their aggregated content.","Content manager 26 is also configured to create view(s) 265 of content before it is requested by a client.","For example, a common view (e.g.","a weekly view) of a user's calendar may be created in advance of the view being requested.","The aggregated content may be organized into different views (e.g.","month view, week view, .",".",".",").","Each different view contains the data used to render the UI for that view.","When the user opens a calendar, a current view may be loaded from memory (e.g.","a cache).","Other stored view data is delivered to the user when requested.","Data views may also be created for other common views (e.g.","contacts, mail, tasks, .",".",".",").","FIG.","3 illustrates a user accessing a cloud service and performing a search across the aggregated content obtained from different content sources.","Display 310 shows a user performing “Search 1” (320) in browser 302 to locate items obtained from different content sources.","The user may select the content sources that they would like searched.","In response to performing “Search 1”, results 330 are shown.","As can be seen, different items from different content sources that were aggregated for the user were located in the search.","Instead of the user having to search each different content source separately, two or more content sources may be searched at a single time.","Display 350 shows user performing a search to locate the message from User 1 across different content sources.","The user may select the content sources that they would like searched.","In response to performing search 360, results 370 are shown.","As can be seen, messages from different content sources and message providers are shown on a single display.","Instead of the user having to search each different content source separately for messages from the user, two or more content sources may be searched at a single time.","FIGS.","4 and 5 illustrate a process for aggregating content and interacting with the aggregated content using a cloud service.","When reading the discussion of the routines presented herein, it should be appreciated that the logical operations of various embodiments are implemented (1) as a sequence of computer implemented acts or program modules running on a computing system and/or (2) as interconnected machine logic circuits or circuit modules within the computing system.","The implementation is a matter of choice dependent on the performance requirements of the computing system implementing the invention.","Accordingly, the logical operations illustrated and making up the embodiments described herein are referred to variously as operations, structural devices, acts or modules.","These operations, structural devices, acts and modules may be implemented in software, in firmware, in special purpose digital logic, and any combination thereof.","While the operations are shown in a particular order, the order of the operations may change, be performed in parallel, depending on the implementation.","FIG.","4 shows a process of a cloud service aggregating content from different content sources.","After a start operation, the process moves to operation 410, where a determination is made as to what content sources a user would like to aggregate.","According to an embodiment, the content sources include content relating to electronic messages, calendars (public, private), contacts, social network content, feed data, search results, and the like.","For example, a user may select to aggregate: electronic messages from different message providers (e.g.","OUTLOOK, GMAIL, YAHOO, .",".",".","), contacts from one or more content providers (e.g.","LINKEDIN, OUTLOOK, FACEBOOK, GMAIL, .",".",".","), calendars from different content providers (e.g.","public or private), and the like.","Transitioning to operation 420, the cloud service obtains the content from the different content sources.","The cloud service uses different protocols to obtain content from the content sources.","For example, the cloud service may obtain content using protocols such as: Internet Message Access Protocol (IMAP), Exchange Web Service (EWS), Messaging Application Programming Interface (MAPI), Exchange Active Sync (EAS), Post Office Protocol (POP), Simple Mail Transfer Protocol (SMTP), as well as many other protocols that may be associated with accessing and interacting with content in a content source.","Some content sources may use their own defined protocol or may modify a common protocol.","The cloud service interacts with each content source using the protocol that is associated with the content source being accessed.","According to an embodiment, the cloud service includes custom provider synchronization interfaces to at least a portion of the content providers.","The provider synchronization interfaces are used to obtain additional content and information from the content source than the content that may be obtained using the standard protocol.","The provider specific interfaces may obtain information form the provider for one or more provider specific features.","Generally, the provider specific interfaces 218 are configured to access features of a content provider that are not available using a common protocol that is associated with the service provider.","For example, while mail may be obtained from a mail service provider using a protocol, the defined protocol may not provide functionality to interface with all of the different features that are provided by the service provider.","The content may be obtained and updated using different methods.","For example, the obtained content may be updated periodically, in response to a notification, or in response to some other event.","Flowing to operation 430, the obtained content is aggregated for the user and stored by the cloud service.","According to an embodiment, each content source that is selected by a user to be aggregated is stored separately within data store 230.In other words, the content from one content source is not mixed with content from another content source.","In this way, the user's content that is stored by the online service may be easily located and each content source may be easily identified.","Transitioning to operation 440, the aggregated content may be processed by the cloud service.","For example, the aggregated content may be augmented with additional content and/or views may be created in advance of the view being requested by a client.","For example, a common view (e.g.","a weekly view) of a user's calendar may be created in advance of the view being requested.","The aggregated content may be organized into different views (e.g.","month view, week view, .",".",". )","and stored for later use.","Each different view created by the cloud service contains the data used to render a User Interface display for that view on a client computing device.","Flowing to operation 450, aggregated content is delivered to a client using a single communication channel (e.g.","a single delivery protocol).","The client interacts with the aggregated data that is stored by cloud service using a single protocol even though cloud service used different protocols to obtain the aggregated content.","According to an embodiment, the client is a thin client (e.g.","a web browser) that uses the cloud service to perform computations and processing relating to the aggregated content.","For example, the cloud service provides PIM services that are typically found in a desktop PIM application.","The process flows to an end operation and returns to processing other actions.","FIG.","5 shows a process of a client interacting with a cloud service that stores aggregated content for the client.","After a start operation, the process moves to operation 510, where the cloud service is accessed.","The cloud service stores the aggregated content for a user.","According to an embodiment, the aggregated content includes content relating to electronic messages, calendar information, and contacts obtained from different content sources.","Other content may be aggregated.","According to an embodiment, the cloud service provides services relating to interacting with and viewing electronic messages, calendar information, and contacts.","Other cloud services may include other aggregated content and provide other services.","Transitioning to operation 520, a user selects a view to display using their client application (e.g.","browser, thin client).","For example, a user may make a selection to display a: calendar view (e.g.","yearly, monthly, weekly, daily); an electronic message, a contact; a task, and the like.","Generally, the view is related to the functionality of the cloud service.","Flowing to operation 530, the aggregated content relating to the view is obtained from the cloud service and the view is displayed at the client.","According to an embodiment, the view is obtained from the cloud service.","For example, when the view has already been created by the cloud service, the view is obtained from a memory (e.g.","a cache or network storage) and delivered to the client for display.","Transitioning to operation 540, a user interacts with the view.","For example, a user may make changes to the view, change the content, create a message, create an event, and the like.","A user may also perform a search across one or more of the different content sources that are included in the aggregated content.","For example, a user may look for messages from particular user across each of their mailboxes, look for contacts obtained from different contact sources, and the like.","Flowing to operation 550, changes made to the aggregated content are synchronized with the external content source.","According to an embodiment, instead of just changing the content at the cloud service, the cloud service changes the content at the cloud service and synchronizes the change with the external content source.","For example, if a user adds a calendar event to a calendar obtained from service provider 1, then the cloud service synchronizes the calendar that is stored by service provider 1.In this way, when a user accesses the calendar using an application supplied by service provider 1, the change to the calendar is shown.","The process flows to an end operation and returns to processing other actions.","FIG.","6 illustrates an exemplary online system for aggregating content from different content sources.","As illustrated, system 1000 includes service 1010, data store 1045, touch screen input device 1050 (e.g.","a tablet/slate), smart phone 1030 and display device 1080.As illustrated, service 1010 is a cloud based and/or enterprise based service that may be configured to provide services, such as services related to various applications (e.g.","whiteboards, searching, games, browsing, locating, productivity services (e.g.","spreadsheets, documents, presentations, charts, messages, and the like)).","The service may be interacted with using different types of input/output.","For example, a user may use speech input, touch input, hardware based input, and the like.","The service may provide speech output that combines pre-recorded speech and synthesized speech.","Functionality of one or more of the services/applications provided by service 1010 may also be configured as a client/server based application.","As illustrated, service 1010 is a multi-tenant service that provides resources 1015 and services to any number of tenants (e.g.","Tenants 1-N).","Multi-tenant service 1010 is a cloud based service that provides resources/services 1015 to tenants subscribed to the service and maintains each tenant's data separately and protected from other tenant data.","System 1000 as illustrated comprises a touch screen input device 1050 (e.g.","a slate/tablet device) and smart phone 1030 that detects when a touch input has been received (e.g.","a finger touching or nearly touching the touch screen).","Any type of touch screen may be utilized that detects a user's touch input.","For example, the touch screen may include one or more layers of capacitive material that detects the touch input.","Other sensors may be used in addition to or in place of the capacitive material.","For example, Infrared (IR) sensors may be used.","According to an embodiment, the touch screen is configured to detect objects that in contact with or above a touchable surface.","Although the term “above” is used in this description, it should be understood that the orientation of the touch panel system is irrelevant.","The term “above” is intended to be applicable to all such orientations.","The touch screen may be configured to determine locations of where touch input is received (e.g.","a starting point, intermediate points and an ending point).","Actual contact between the touchable surface and the object may be detected by any suitable means, including, for example, by a vibration sensor or microphone coupled to the touch panel.","A non-exhaustive list of examples for sensors to detect contact includes pressure-based mechanisms, micro-machined accelerometers, piezoelectric devices, capacitive sensors, resistive sensors, inductive sensors, laser vibrometers, and LED vibrometers.","According to an embodiment, smart phone 1030, touch screen input device 1050, and device 1080 are configured with multimodal input/output and each include an application (1031, 1051, 1081).","As illustrated, touch screen input device 1050, smart phone 1030, and display device 1080 shows exemplary displays 1052/1032/1082 showing the use of an application, such as an application that is accessing aggregated content that is associated with a user and stored by service 1010.Data may be stored on a device (e.g.","smart phone 1030, touch screen input device 1050 and/or at some other location (e.g.","network data store 1045).","Data store 1045, or some other store, may be used to store aggregated content as well as other data.","The applications used by the devices may be client based applications, server based applications, cloud based applications and/or some combination.","According to an embodiment, display device 1080 is a device such as a MICROSOFT XBOX coupled to a display.","Content manager 26 is configured to perform operations relating to aggregating content as described herein.","The embodiments and functionalities described herein may operate via a multitude of computing systems including, without limitation, desktop computer systems, wired and wireless computing systems, mobile computing systems (e.g., mobile telephones, netbooks, tablet or slate type computers, notebook computers, and laptop computers), hand-held devices, multiprocessor systems, microprocessor-based or programmable consumer electronics, minicomputers, and mainframe computers.","In addition, the embodiments and functionalities described herein may operate over distributed systems (e.g., cloud-based computing systems), where application functionality, memory, data storage and retrieval and various processing functions may be operated remotely from each other over a distributed computing network, such as the Internet or an intranet.","User interfaces and information of various types may be displayed via on-board computing device displays or via remote display units associated with one or more computing devices.","For example user interfaces and information of various types may be displayed and interacted with on a wall surface onto which user interfaces and information of various types are projected.","Interaction with the multitude of computing systems with which embodiments of the invention may be practiced include, keystroke entry, touch screen entry, voice or other audio entry, gesture entry where an associated computing device is equipped with detection (e.g., camera) functionality for capturing and interpreting user gestures for controlling the functionality of the computing device, and the like.","FIGS.","7-9 and the associated descriptions provide a discussion of a variety of operating environments in which embodiments of the invention may be practiced.","However, the devices and systems illustrated and discussed with respect to FIGS.","7-9 are for purposes of example and illustration and are not limiting of a vast number of computing device configurations that may be utilized for practicing embodiments of the invention, described herein.","FIG.","7 is a block diagram illustrating physical components (i.e., hardware) of a computing device 1100 with which embodiments of the invention may be practiced.","The computing device components described below may be suitable for the computing devices described above.","In a basic configuration, the computing device 1100 may include at least one processing unit 1102 and a system memory 1104.Depending on the configuration and type of computing device, the system memory 1104 may comprise, but is not limited to, volatile storage (e.g., random access memory), non-volatile storage (e.g., read-only memory), flash memory, or any combination of such memories.","The system memory 1104 may include an operating system 1105 and one or more program modules 1106 suitable for running software applications 1120 such as the content manager 26.The operating system 1105, for example, may be suitable for controlling the operation of the computing device 1100.Furthermore, embodiments of the invention may be practiced in conjunction with a graphics library, other operating systems, or any other application program and is not limited to any particular application or system.","This basic configuration is illustrated in FIG.","7 by those components within a dashed line 1108.The computing device 1100 may have additional features or functionality.","For example, the computing device 1100 may also include additional data storage devices (removable and/or non-removable) such as, for example, magnetic disks, optical disks, or tape.","Such additional storage is illustrated in FIG.","7 by a removable storage device 1109 and a non-removable storage device 1110.As stated above, a number of program modules and data files may be stored in the system memory 1104.While executing on the processing unit 1102, the program modules 1106 (e.g., the content manager 26) may perform processes including, but not limited to, one or more of the stages of the methods and processes illustrated in the figures.","Other program modules that may be used in accordance with embodiments of the present invention may include electronic mail and contacts applications, word processing applications, spreadsheet applications, database applications, slide presentation applications, drawing or computer-aided application programs, etc.","Furthermore, embodiments of the invention may be practiced in an electrical circuit comprising discrete electronic elements, packaged or integrated electronic chips containing logic gates, a circuit utilizing a microprocessor, or on a single chip containing electronic elements or microprocessors.","For example, embodiments of the invention may be practiced via a system-on-a-chip (SOC) where each or many of the components illustrated in FIG.","7 may be integrated onto a single integrated circuit.","Such an SOC device may include one or more processing units, graphics units, communications units, system virtualization units and various application functionality all of which are integrated (or “burned”) onto the chip substrate as a single integrated circuit.","When operating via an SOC, the functionality, described herein, with respect to the content manager 26 may be operated via application-specific logic integrated with other components of the computing device 1100 on the single integrated circuit (chip).","Embodiments of the invention may also be practiced using other technologies capable of performing logical operations such as, for example, AND, OR, and NOT, including but not limited to mechanical, optical, fluidic, and quantum technologies.","In addition, embodiments of the invention may be practiced within a general purpose computer or in any other circuits or systems.","The computing device 1100 may also have one or more input device(s) 1112 such as a keyboard, a mouse, a pen, a sound input device, a touch input device, etc.","The output device(s) 1114 such as a display, speakers, a printer, etc.","may also be included.","The aforementioned devices are examples and others may be used.","The computing device 1100 may include one or more communication connections 1116 allowing communications with other computing devices 1118.Examples of suitable communication connections 1116 include, but are not limited to, RF transmitter, receiver, and/or transceiver circuitry; universal serial bus (USB), parallel, and/or serial ports.","The term computer readable media as used herein may include computer storage media.","Computer storage media may include volatile and nonvolatile, removable and non-removable media implemented in any method or technology for storage of information, such as computer readable instructions, data structures, or program modules.","The system memory 1104, the removable storage device 1109, and the non-removable storage device 1110 are all computer storage media examples (i.e., memory storage.)","Computer storage media may include RAM, ROM, electrically erasable read-only memory (EEPROM), flash memory or other memory technology, CD-ROM, digital versatile disks (DVD) or other optical storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other article of manufacture which can be used to store information and which can be accessed by the computing device 1100.Any such computer storage media may be part of the computing device 1100.Computer storage media does not include a carrier wave or other propagated or modulated data signal.","Communication media may be embodied by computer readable instructions, data structures, program modules, or other data in a modulated data signal, such as a carrier wave or other transport mechanism, and includes any information delivery media.","The term “modulated data signal” may describe a signal that has one or more characteristics set or changed in such a manner as to encode information in the signal.","By way of example, and not limitation, communication media may include wired media such as a wired network or direct-wired connection, and wireless media such as acoustic, radio frequency (RF), infrared, and other wireless media.","FIGS.","8A and 8B illustrate a mobile computing device 1200, for example, a mobile telephone, a smart phone, a tablet personal computer, a laptop computer, and the like, with which embodiments of the invention may be practiced.","With reference to FIG.","8A, one embodiment of a mobile computing device 1200 for implementing the embodiments is illustrated.","In a basic configuration, the mobile computing device 1200 is a handheld computer having both input elements and output elements.","The mobile computing device 1200 typically includes a display 1205 and one or more input buttons 1210 that allow the user to enter information into the mobile computing device 1200.The display 1205 of the mobile computing device 1200 may also function as an input device (e.g., a touch screen display).","If included, an optional side input element 1215 allows further user input.","The side input element 1215 may be a rotary switch, a button, or any other type of manual input element.","In alternative embodiments, mobile computing device 1200 may incorporate more or less input elements.","For example, the display 1205 may not be a touch screen in some embodiments.","In yet another alternative embodiment, the mobile computing device 1200 is a portable phone system, such as a cellular phone.","The mobile computing device 1200 may also include an optional keypad 1235.Optional keypad 1235 may be a physical keypad or a “soft” keypad generated on the touch screen display.","In various embodiments, the output elements include the display 1205 for showing a graphical user interface (GUI), a visual indicator 1220 (e.g., a light emitting diode), and/or an audio transducer 1225 (e.g., a speaker).","In some embodiments, the mobile computing device 1200 incorporates a vibration transducer for providing the user with tactile feedback.","In yet another embodiment, the mobile computing device 1200 incorporates input and/or output ports, such as an audio input (e.g., a microphone jack), an audio output (e.g., a headphone jack), and a video output (e.g., a HDMI port) for sending signals to or receiving signals from an external device.","FIG.","8B is a block diagram illustrating the architecture of one embodiment of a mobile computing device.","That is, the mobile computing device 1200 can incorporate a system 1202 (i.e., an architecture) to implement some embodiments.","In one embodiment, the system 1202 is implemented as a “smart phone” capable of running one or more applications (e.g., browser, e-mail, calendaring, contact managers, messaging clients, games, and media clients/players).","In some embodiments, the system 1202 is integrated as a computing device, such as an integrated personal digital assistant (PDA) and wireless phone.","One or more application programs 1266 may be loaded into the memory 1262 and run on or in association with the operating system 1264.Examples of the application programs include phone dialer programs, e-mail programs, personal information management (PIM) programs, word processing programs, spreadsheet programs, Internet browser programs, messaging programs, and so forth.","The system 1202 also includes a non-volatile storage area 1268 within the memory 1262.The non-volatile storage area 1268 may be used to store persistent information that should not be lost if the system 1202 is powered down.","The application programs 1266 may use and store information in the non-volatile storage area 1268, such as e-mail or other messages used by an e-mail application, and the like.","A synchronization application (not shown) also resides on the system 1202 and is programmed to interact with a corresponding synchronization application resident on a host computer to keep the information stored in the non-volatile storage area 1268 synchronized with corresponding information stored at the host computer.","As should be appreciated, other applications may be loaded into the memory 1262 and run on the mobile computing device 1200, including the content manager 26 as described herein.","The system 1202 has a power supply 1270, which may be implemented as one or more batteries.","The power supply 1270 might further include an external power source, such as an AC adapter or a powered docking cradle that supplements or recharges the batteries.","The system 1202 may also include a radio 1272 that performs the function of transmitting and receiving radio frequency communications.","The radio 1272 facilitates wireless connectivity between the system 1202 and the “outside world,” via a communications carrier or service provider.","Transmissions to and from the radio 1272 are conducted under control of the operating system 1264.In other words, communications received by the radio 1272 may be disseminated to the application programs 1266 via the operating system 1264, and vice versa.","The visual indicator 1220 may be used to provide visual notifications, and/or an audio interface 1274 may be used for producing audible notifications via the audio transducer 1225.In the illustrated embodiment, the visual indicator 1220 is a light emitting diode (LED) and the audio transducer 1225 is a speaker.","These devices may be directly coupled to the power supply 1270 so that when activated, they remain on for a duration dictated by the notification mechanism even though the processor 1260 and other components might shut down for conserving battery power.","The LED may be programmed to remain on indefinitely until the user takes action to indicate the powered-on status of the device.","The audio interface 1274 is used to provide audible signals to and receive audible signals from the user.","For example, in addition to being coupled to the audio transducer 1225, the audio interface 1274 may also be coupled to a microphone to receive audible input, such as to facilitate a telephone conversation.","In accordance with embodiments of the present invention, the microphone may also serve as an audio sensor to facilitate control of notifications, as will be described below.","The system 1202 may further include a video interface 1276 that enables an operation of an on-board camera to record still images, video stream, and the like.","A mobile computing device 1200 implementing the system 1202 may have additional features or functionality.","For example, the mobile computing device 1200 may also include additional data storage devices (removable and/or non-removable) such as, magnetic disks, optical disks, or tape.","Such additional storage is illustrated in FIG.","8B by the non-volatile storage area 1268.Mobile computing device 1200 may also include peripheral device port 1230.Data/information generated or captured by the mobile computing device 1200 and stored via the system 1202 may be stored locally on the mobile computing device 1200, as described above, or the data may be stored on any number of storage media that may be accessed by the device via the radio 1272 or via a wired connection between the mobile computing device 1200 and a separate computing device associated with the mobile computing device 1200, for example, a server computer in a distributed computing network, such as the Internet.","As should be appreciated such data/information may be accessed via the mobile computing device 1200 via the radio 1272 or via a distributed computing network.","Similarly, such data/information may be readily transferred between computing devices for storage and use according to well-known data/information transfer and storage means, including electronic mail and collaborative data/information sharing systems.","FIG.","9 illustrates an embodiment of an architecture of an exemplary system, as described above.","Content developed, interacted with, or edited in association with the content manager 26 may be stored in different communication channels or other storage types.","For example, various documents may be stored using a directory service 1322, a web portal 1324, a mailbox service 1326, an instant messaging store 1328, or a social networking site 1330.The content manager 26 may use any of these types of systems or the like for enabling data utilization, as described herein.","A server 1320 may provide the content manager 26 to clients.","As one example, the server 1320 may be a web server providing the content manager 26 over the web.","The server 1320 may provide the content manager 26 over the web to clients through a network 1315.By way of example, the client computing device may be implemented as the computing device 1100 and embodied in a personal computer, a tablet computing device 1310 and/or a mobile computing device 1200 (e.g., a smart phone).","Any of these embodiments of the client computing device 1100, 1310, and 1200 may obtain content from the store 1316.Embodiments of the present invention, for example, are described above with reference to block diagrams and/or operational illustrations of methods, systems, and computer program products according to embodiments of the invention.","The functions/acts noted in the blocks may occur out of the order as shown in any flowchart.","For example, two blocks shown in succession may in fact be executed substantially concurrently or the blocks may sometimes be executed in the reverse order, depending upon the functionality/acts involved.","The description and illustration of one or more embodiments provided in this application are not intended to limit or restrict the scope of the invention as claimed in any way.","The embodiments, examples, and details provided in this application are considered sufficient to convey possession and enable others to make and use the best mode of claimed invention.","The claimed invention should not be construed as being limited to any embodiment, example, or detail provided in this application.","Regardless of whether shown and described in combination or separately, the various features (both structural and methodological) are intended to be selectively included or omitted to produce an embodiment with a particular set of features.","Having been provided with the description and illustration of the present application, one skilled in the art may envision variations, modifications, and alternate embodiments falling within the spirit of the broader aspects of the general inventive concept embodied in this application that do not depart from the broader scope of the claimed invention."]],"string":"[\n [\n \"AGGREGATING CONTENT FROM DIFFERENT CONTENT SOURCES AT A CLOUD SERVICE\",\n \"A cloud service stores and aggregates content that is obtained from different content sources using different protocols.\",\n \"For example, the content may include electronic messages, calendar information, contacts, social network content, feed data, search results, and the like.\",\n \"The cloud service aggregates content for each user based on the user's configuration settings.\",\n \"The cloud service may perform processing on the aggregated content before it is delivered and displayed to the user on the client device.\",\n \"For example, one or more views may be generated and stored by the cloud service before the view is requested from the client.\",\n \"Changes made to the aggregated content on the client may be synchronized with the content source.\",\n \"Searches may be made across all or a portion of the different content sources that are aggregated for a user.\"\n ],\n [\n \"1.A method for aggregating content at a cloud service, comprising: obtaining content from different content sources that use different protocols using the cloud service; aggregating the content at the cloud service and associating the aggregated content with a user; storing the aggregated content for the user at the cloud service; and using a single delivery protocol to deliver aggregated content to a client computing device regardless of the different protocols used by the cloud service to obtain the content.\",\n \"2.The method of claim 1, wherein obtaining the content from the different content sources that use the different protocols comprises obtaining electronic messages, calendar information, and contact information associated with the user.\",\n \"3.The method of claim 1, wherein obtaining the content from the different content sources that use the different protocols comprises obtaining at least one of: social network content obtained from a social network; search results obtained from a search engine; or feed content.\",\n \"4.The method of claim 1, further comprising generating different views of the aggregated content at the cloud service and storing the different views at the cloud service.\",\n \"5.The method of claim 1, wherein storing the aggregated content for the user at the cloud service comprises storing each different content source as separate content within a data storage.\",\n \"6.The method of claim 1, further comprising determining when a change is made to the aggregated content and synchronizing the change back to the content source where the content was obtained.\",\n \"7.The method of claim 1, further comprising obtaining provider specific information from at least one of the content sources in addition to using a synchronization protocol specified by the provider of the content source.\",\n \"8.The method of claim 1, further comprising receiving a search query from a client device and performing a search across at least a portion of the different content sources aggregated for the user.\",\n \"9.The method of claim 1, further comprising receiving a search query from a client device and performing a search using the search query across different mail sources to locate messages from different mail providers.\",\n \"10.A computer-readable medium storing computer-executable instructions for aggregating content at a cloud service, comprising: obtaining content from different content sources using the cloud service including electronic message content, calendar content, and contact content that use different protocols; aggregating the content at the cloud service and associating the aggregated content with a user; storing the aggregated content for the user at the cloud service; and using a single delivery protocol to deliver aggregated content to a client computing device regardless of the different protocols used by the cloud service to obtain the content.\",\n \"11.The computer-readable medium of claim 10, further comprising generating different views of the aggregated content at the cloud service and storing the different views at the cloud service.\",\n \"12.The computer-readable medium of claim 10, wherein storing the aggregated content for the user at the cloud service comprises storing each different content source as separate content within a data storage.\",\n \"13.The computer-readable medium of claim 10, further comprising determining when a change is made to the aggregated content and synchronizing the change back to the content source where the content was obtained.\",\n \"14.The computer-readable medium of claim 10, further comprising obtaining provider specific information from at least one of the content sources in addition to using a synchronization protocol specified by the provider of the content source.\",\n \"15.The computer-readable medium of claim 10, further comprising receiving a search query from a client device and performing a search across at least a portion of the different content sources aggregated for the user.\",\n \"16.The computer-readable medium of claim 10, further comprising receiving a search query from a client device and performing a search using the search query across different mail sources to locate messages from different mail providers.\",\n \"17.A system for aggregating content at a cloud service, comprising: a processor and memory; an operating environment executing using the processor; and an content manager that is configured to perform actions comprising: obtaining content from different content sources using the cloud service including electronic message content, calendar content, and contact content that use different protocols; aggregating the content at the cloud service and associating the aggregated content with a user; storing the aggregated content for the user at the cloud service; generating different views of the aggregated content at the cloud service; and using a single delivery protocol to deliver one of the views to a client computing device.\",\n \"18.The system of claim 17, wherein storing the aggregated content for the user at the cloud service comprises storing each different content source as separate content within a data storage.\",\n \"19.The system of claim 17, further comprising determining when a change is made to the aggregated content and synchronizing the change back to the content source where the content was obtained.\",\n \"20.The system of claim 17, further comprising obtaining provider specific information from at least one of the content sources in addition to using a synchronization protocol specified by the provider of the content source.\"\n ],\n [\n \" BACKGROUND Personal Information Manager (PIM) applications are commonly used by computer users.\",\n \"PIM applications are used for recording, tracking, and managing personal information for a user.\",\n \"For example, a user may use a PIM application to access email, contacts and calendar information from one or more providers.\",\n \"The content that is used by the PIM application may be obtained from a variety of different content sources.\"\n ],\n [\n \" SUMMARY This Summary is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description.\",\n \"This Summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.\",\n \"A cloud service stores and aggregates content that is obtained from different content sources using different protocols.\",\n \"For example, the content may include electronic messages, calendar information, contacts, social network content, feed data, search results, and the like.\",\n \"The cloud service aggregates content for a user based on the user's configuration settings.\",\n \"For example, a user may configure their personal information manager (PIM) application to include mail from different mail providers.\",\n \"The user may also configure their PIM application to include contacts from a social network, as well as calendar events from one or more calendars or content sources.\",\n \"Instead of the client PIM application accessing each of the individual content sources and incorporating the content into the PIM application, the cloud service obtains and aggregates the content obtained from the different content sources.\",\n \"The cloud service may perform processing on the aggregated content before it is delivered and displayed to the user on the client device.\",\n \"For example, one or more views may be generated and stored by the cloud service before the view is requested from the client.\",\n \"Changes made to the aggregated content on the client may be synchronized with the content source.\",\n \"For example, in response to a user making a change to an email that is associated with a different email provider, the change is synchronized with the different email provider.\",\n \"Searches may be made across all or a portion of the different content sources that are aggregated for a user.\",\n \"For example, a user may view the messages from a particular user regardless of the message provider providing the content to the user.\",\n \"Similarly, a user may perform a general search across each of the different content sources to locate items matching a search query.\"\n ],\n [\n \"CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of, and claims priority to, non-provisional U.S. application Ser.\",\n \"No.\",\n \"13/925,599, filed Jun.\",\n \"24, 2013, which application is incorporated herein by reference in their entirety.\",\n \"BACKGROUND Personal Information Manager (PIM) applications are commonly used by computer users.\",\n \"PIM applications are used for recording, tracking, and managing personal information for a user.\",\n \"For example, a user may use a PIM application to access email, contacts and calendar information from one or more providers.\",\n \"The content that is used by the PIM application may be obtained from a variety of different content sources.\",\n \"SUMMARY This Summary is provided to introduce a selection of concepts in a simplified form that are further described below in the Detailed Description.\",\n \"This Summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.\",\n \"A cloud service stores and aggregates content that is obtained from different content sources using different protocols.\",\n \"For example, the content may include electronic messages, calendar information, contacts, social network content, feed data, search results, and the like.\",\n \"The cloud service aggregates content for a user based on the user's configuration settings.\",\n \"For example, a user may configure their personal information manager (PIM) application to include mail from different mail providers.\",\n \"The user may also configure their PIM application to include contacts from a social network, as well as calendar events from one or more calendars or content sources.\",\n \"Instead of the client PIM application accessing each of the individual content sources and incorporating the content into the PIM application, the cloud service obtains and aggregates the content obtained from the different content sources.\",\n \"The cloud service may perform processing on the aggregated content before it is delivered and displayed to the user on the client device.\",\n \"For example, one or more views may be generated and stored by the cloud service before the view is requested from the client.\",\n \"Changes made to the aggregated content on the client may be synchronized with the content source.\",\n \"For example, in response to a user making a change to an email that is associated with a different email provider, the change is synchronized with the different email provider.\",\n \"Searches may be made across all or a portion of the different content sources that are aggregated for a user.\",\n \"For example, a user may view the messages from a particular user regardless of the message provider providing the content to the user.\",\n \"Similarly, a user may perform a general search across each of the different content sources to locate items matching a search query.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS FIG.\",\n \"1 shows a system including a cloud service that aggregates content for different users that is obtained from different content sources; FIG.\",\n \"2 illustrates a synchronization engine included in a cloud service that augments content that is obtained from different content sources; FIG.\",\n \"3 illustrates a user accessing a cloud service and performing a search across the aggregated content obtained from different content sources; FIG.\",\n \"4 shows a process of a cloud service aggregating content from different content sources; FIG.\",\n \"5 shows a process of a client interacting with a cloud service that stores aggregated content for the client; FIG.\",\n \"6 illustrates an exemplary online system for aggregating content from different content sources; and FIGS.\",\n \"7, 8A, 8B, and 9 and the associated descriptions provide a discussion of a variety of operating environments in which embodiments of the invention may be practiced.\",\n \"DETAILED DESCRIPTION Referring now to the drawings, in which like numerals represent like elements, various embodiments will be described.\",\n \"FIG.\",\n \"1 shows a system including a cloud service that aggregates content for different users that is obtained from different content sources.\",\n \"As illustrated, system 100 includes application(s) 110, content sources 120, search 130, cloud service 105, aggregated content 135, content manager 26, other remote clients 140, and computing device 150.Content manager 26 is configured to aggregate content that is obtained from different content sources.\",\n \"According to an embodiment, the content is aggregated by the Cloud (e.g.\",\n \"“online”) service 105 and is stored by the cloud service 105.For example, the aggregated content may be stored in a data store (e.g.\",\n \"aggregated content 135).\",\n \"The content sources 120 that are aggregated may include many different types of content.\",\n \"For example, the content sources may include content relating to electronic messages, calendars (public, private), contacts, social network content, feed data, search results, and the like.\",\n \"Using content manager 26, cloud service 105 aggregates content for different users based on the configuration settings that are associated with a user.\",\n \"For example, a user may configure their personal information manager (PIM) application to include mail, contacts, and calendars from different service providers.\",\n \"The user may also configure their PIM application to include contacts from a social network, as well as calendar events from one or more content sources.\",\n \"Instead of a client PIM application accessing each of the individual content providers and storing the content, cloud service 105 obtains and aggregates the content that is obtained from the different content sources for the user.\",\n \"According to an embodiment, service 105 stores each user's data that is obtained from each content source separately.\",\n \"According to an embodiment, content manager 26 may be configured to augment the aggregated content 135 to include additional content.\",\n \"For example, calendar events may be augmented to include: traffic information, driving directions, news information, weather information, related events, and the like.\",\n \"Generally, the content is augmented to include additional information relating to the content.\",\n \"Cloud service 105 may augment the aggregated content differently based on the type of the content being augmented.\",\n \"For example, electronic messages may be augmented differently as compared to when augmenting calendar events or contact cards.\",\n \"As illustrated in FIG.\",\n \"1, computing device 150 shows Calendar 155 that displays a weekly view of a calendar that includes different events that may be obtained from different content sources.\",\n \"In the current example, augmented content is shown on April 16th.\",\n \"The augmented content and the aggregated content may include content from different content sources.\",\n \"For example, the content may include traffic information, driving directions, location information ,restaurant information, social network posts, news feeds, calendar content, mail content, and the like.\",\n \"Changes made to the aggregated content on the client may be synchronized with the external content source.\",\n \"For example, in response to a user making a change to an email that is associated with a different email provider, content manager 26 synchronizes the change with the content stored by the different email provider.\",\n \"Cloud service 105 may perform processing on the aggregated content before it is displayed or delivered to the user on a client computing device.\",\n \"For example, one or more views may be generated by content manager 26 and stored by the cloud service 105 before the view is requested from the client computing device.\",\n \"In order to facilitate communication with content manager 26, one or more callback routines, may be implemented.\",\n \"Application(s) 110 may be a variety of applications, such as PIM applications, business productivity applications, entertainment applications, music applications, travel applications, video applications, and the like.\",\n \"Generally, application(s) 110 may be any application that includes content that may be aggregated.\",\n \"The application(s) 110 may be configured to receive different types of input (e.g.\",\n \"speech input, touch input, keyboard input (e.g.\",\n \"a physical keyboard and/or Software Input Panel (SIP)) and/or other types of input.\",\n \"System 100 as illustrated comprises one or more touch screen input devices, such as computing device 150, that detects when a touch input has been received (e.g.\",\n \"a finger touching or nearly touching the touch screen).\",\n \"Any type of touch screen may be utilized that detects a user's touch input.\",\n \"For example, the touch screen may include one or more layers of capacitive material that detects the touch input.\",\n \"More details are provided below.\",\n \"FIG.\",\n \"2 illustrates a synchronization engine included in a cloud service that augments content that is obtained from different content sources.\",\n \"As illustrated, system 200 includes content sources 120, synchronization engine 220, content manager 26 including aggregator 250 and augmenter 260, data store 230, cloud service 105, client 270, and other clients 275.Instead of a client application connecting with each different content provider to obtain content, service 105 using content manager 26 obtains and aggregates content from content sources 120.According to an embodiment, a client (e.g.\",\n \"client 270) may use a single protocol to communicate with the different content obtained by cloud service 105.As discussed above, content sources 120 may include many different content sources.\",\n \"For example, content sources 120 may include: feed sources; Personal Information Management (PIM) sources (e.g.\",\n \"OUTLOOK, GMAIL, YAHOO) that include content relating to electronic messages, calendars, tasks, and the like; social network sources (e.g.\",\n \"TWITTER, FACEBOOK, LINKEDIN .\",\n \".\",\n \".\",\n \"); weather sources; entertainment sources; map and navigation sources; public calendar sources, private calendar sources, and the like.\",\n \"Generally, a content source may be any source from which content may be obtained from and aggregated for a user.\",\n \"Each client (user) may determine what content they would like aggregated.\",\n \"For example, when a user first accesses cloud service 105, they may configure what content sources they would like to include (e.g.\",\n \"mail from GMAIL and YAHOO, as well as OUTLOOK email).\",\n \"The user may also select social network sources (e.g.\",\n \"YAMMER, SHAREPOINT, FACEBOOK, TWITTER, .\",\n \".\",\n \".\",\n \"), feeds, and the like.\",\n \"For example, the use may select to include contacts and contact info, FACEBOOK, GMAIL, TWITTER, LINKEDIN, and the like.\",\n \"In response to the user selections of the content sources, content manager 26 uses aggregator 250 to obtain the content from the content source.\",\n \"The retrieved content is stored in the cloud service 105 in data store 230.According to an embodiment, each content source that is selected by a user to be aggregated is stored separately within data store 230.In other words, the content from one content source is not mixed with content from another content source.\",\n \"According to another embodiment, the content sources may be stored mixed within data store 230.Aggregator 250 may obtain content from the content sources in response to different events.\",\n \"For example, aggregator 250 may obtain content periodically, in response to a notification, or in response to some other event.\",\n \"Synchronization engine 220 is configured to act an interface between the cloud service 105 and the content sources.\",\n \"Different content sources may use different protocols 216 to allow access to content in a content source.\",\n \"For example, the Internet Message Access Protocol (IMAP) is a generic protocol for email that may be used by one or more content sources.\",\n \"Other common protocols include Exchange Web Service (EWS), Messaging Application Programming Interface (MAPI), Exchange Active Sync (EAS), Post Office Protocol (POP), Simple Mail Transfer Protocol (SMTP), as well as many other protocols that may be associated with accessing and interacting with content in a content source.\",\n \"Some content sources may use their own defined protocol or may modify a common protocol.\",\n \"Synchronization engine 220 interacts with each content source using the protocol that is associated with the content source being accessed.\",\n \"Synchronization engine 220 is configured to aggregate provider specific content.\",\n \"Instead of just using a generic protocol (e.g.\",\n \"IMAP, MAPI, .\",\n \".\",\n \". )\",\n \"to obtain content from each content source, specific provider synchronization interfaces 218 may be created and used to obtain additional content and information from the content source.\",\n \"For example, the provider specific interfaces 218 may obtain information form the provider for one or more provider specific features.\",\n \"For example, a provider specific interface to the GMAIL service may obtain labels in GMAIL and map that information to the same feature or another feature used when a client accesses the GMAIL content (e.g.\",\n \"map label in GMAIL to a mail folder).\",\n \"According to another embodiment, the provider synchronization interfaces 218 may be configured to maintain the use of provider specific features.\",\n \"Generally, the provider specific interfaces 218 are configured to access features of a content provider that are not available using a common protocol that is associated with the service provider.\",\n \"For example, while mail may be obtained from a mail service provider using a protocol, the defined protocol may not provide functionality to interface with all of the different features that are provided by the service provider.\",\n \"According to an embodiment, synchronization engine 220 is configured to allow two-way synchronization between the different content sources and data store 230 in the cloud service.\",\n \"For example, a user (e.g.\",\n \"client 270) may make a change to an email that was obtained from a different mail service provider that is synchronized back to the different service provider.\",\n \"This is different from traditional applications that download the content to an application but do not synchronize changes back to the service after a change is made.\",\n \"As another example, a user may add a folder in the client that translates in mapping the folder to a label.\",\n \"The provider synchronization interface logic is specific logic that applies to each content provider.\",\n \"Content may be synchronized to different fidelity levels.\",\n \"The aggregated content for a user may be augmented with additional content using augmenter 260.The content may be augmented in response to an item being created (e.g.\",\n \"an appointment, a message) and/or augmented at some other time.\",\n \"For example, the content may be aggregated when the user opens a view of the content.\",\n \"The following examples of augmenting content are examples, and are not intended to be limiting.\",\n \"A view of a user's calendar may be augmented using public calendar feeds.\",\n \"For example, the calendar feeds could be sports calendars, school calendars, social experiences, home schedules, and the like.\",\n \"Information relating to the calendar may also be obtained from other sources.\",\n \"A search may automatically be performed to locate content that is referenced in a message, in a calendar, in a task, and the like.\",\n \"For example, when viewing the calendar that includes a schedule of games, the scores of the games may automatically be added to the view after performing a search for the score.\",\n \"Instead of each client having to obtain the content directly from the content sources using the different protocols and storing the aggregated information on the client computing device, the cloud service 105 stores the content, performs the aggregation, and delivers aggregated content to a client using a single communication channel (a single delivery protocol).\",\n \"Client 270 interacts with the cloud service 105 using a single protocol even though cloud service used many different protocols to obtain the aggregated content.\",\n \"According to an embodiment, client 270 is a thin and portable client (e.g.\",\n \"it does not need to include the synchronization logic, protocols and other functionality that cloud service 105 includes).\",\n \"Other clients 275 also communicate with cloud service 105 to access their aggregated content.\",\n \"Content manager 26 is also configured to create view(s) 265 of content before it is requested by a client.\",\n \"For example, a common view (e.g.\",\n \"a weekly view) of a user's calendar may be created in advance of the view being requested.\",\n \"The aggregated content may be organized into different views (e.g.\",\n \"month view, week view, .\",\n \".\",\n \".\",\n \").\",\n \"Each different view contains the data used to render the UI for that view.\",\n \"When the user opens a calendar, a current view may be loaded from memory (e.g.\",\n \"a cache).\",\n \"Other stored view data is delivered to the user when requested.\",\n \"Data views may also be created for other common views (e.g.\",\n \"contacts, mail, tasks, .\",\n \".\",\n \".\",\n \").\",\n \"FIG.\",\n \"3 illustrates a user accessing a cloud service and performing a search across the aggregated content obtained from different content sources.\",\n \"Display 310 shows a user performing “Search 1” (320) in browser 302 to locate items obtained from different content sources.\",\n \"The user may select the content sources that they would like searched.\",\n \"In response to performing “Search 1”, results 330 are shown.\",\n \"As can be seen, different items from different content sources that were aggregated for the user were located in the search.\",\n \"Instead of the user having to search each different content source separately, two or more content sources may be searched at a single time.\",\n \"Display 350 shows user performing a search to locate the message from User 1 across different content sources.\",\n \"The user may select the content sources that they would like searched.\",\n \"In response to performing search 360, results 370 are shown.\",\n \"As can be seen, messages from different content sources and message providers are shown on a single display.\",\n \"Instead of the user having to search each different content source separately for messages from the user, two or more content sources may be searched at a single time.\",\n \"FIGS.\",\n \"4 and 5 illustrate a process for aggregating content and interacting with the aggregated content using a cloud service.\",\n \"When reading the discussion of the routines presented herein, it should be appreciated that the logical operations of various embodiments are implemented (1) as a sequence of computer implemented acts or program modules running on a computing system and/or (2) as interconnected machine logic circuits or circuit modules within the computing system.\",\n \"The implementation is a matter of choice dependent on the performance requirements of the computing system implementing the invention.\",\n \"Accordingly, the logical operations illustrated and making up the embodiments described herein are referred to variously as operations, structural devices, acts or modules.\",\n \"These operations, structural devices, acts and modules may be implemented in software, in firmware, in special purpose digital logic, and any combination thereof.\",\n \"While the operations are shown in a particular order, the order of the operations may change, be performed in parallel, depending on the implementation.\",\n \"FIG.\",\n \"4 shows a process of a cloud service aggregating content from different content sources.\",\n \"After a start operation, the process moves to operation 410, where a determination is made as to what content sources a user would like to aggregate.\",\n \"According to an embodiment, the content sources include content relating to electronic messages, calendars (public, private), contacts, social network content, feed data, search results, and the like.\",\n \"For example, a user may select to aggregate: electronic messages from different message providers (e.g.\",\n \"OUTLOOK, GMAIL, YAHOO, .\",\n \".\",\n \".\",\n \"), contacts from one or more content providers (e.g.\",\n \"LINKEDIN, OUTLOOK, FACEBOOK, GMAIL, .\",\n \".\",\n \".\",\n \"), calendars from different content providers (e.g.\",\n \"public or private), and the like.\",\n \"Transitioning to operation 420, the cloud service obtains the content from the different content sources.\",\n \"The cloud service uses different protocols to obtain content from the content sources.\",\n \"For example, the cloud service may obtain content using protocols such as: Internet Message Access Protocol (IMAP), Exchange Web Service (EWS), Messaging Application Programming Interface (MAPI), Exchange Active Sync (EAS), Post Office Protocol (POP), Simple Mail Transfer Protocol (SMTP), as well as many other protocols that may be associated with accessing and interacting with content in a content source.\",\n \"Some content sources may use their own defined protocol or may modify a common protocol.\",\n \"The cloud service interacts with each content source using the protocol that is associated with the content source being accessed.\",\n \"According to an embodiment, the cloud service includes custom provider synchronization interfaces to at least a portion of the content providers.\",\n \"The provider synchronization interfaces are used to obtain additional content and information from the content source than the content that may be obtained using the standard protocol.\",\n \"The provider specific interfaces may obtain information form the provider for one or more provider specific features.\",\n \"Generally, the provider specific interfaces 218 are configured to access features of a content provider that are not available using a common protocol that is associated with the service provider.\",\n \"For example, while mail may be obtained from a mail service provider using a protocol, the defined protocol may not provide functionality to interface with all of the different features that are provided by the service provider.\",\n \"The content may be obtained and updated using different methods.\",\n \"For example, the obtained content may be updated periodically, in response to a notification, or in response to some other event.\",\n \"Flowing to operation 430, the obtained content is aggregated for the user and stored by the cloud service.\",\n \"According to an embodiment, each content source that is selected by a user to be aggregated is stored separately within data store 230.In other words, the content from one content source is not mixed with content from another content source.\",\n \"In this way, the user's content that is stored by the online service may be easily located and each content source may be easily identified.\",\n \"Transitioning to operation 440, the aggregated content may be processed by the cloud service.\",\n \"For example, the aggregated content may be augmented with additional content and/or views may be created in advance of the view being requested by a client.\",\n \"For example, a common view (e.g.\",\n \"a weekly view) of a user's calendar may be created in advance of the view being requested.\",\n \"The aggregated content may be organized into different views (e.g.\",\n \"month view, week view, .\",\n \".\",\n \". )\",\n \"and stored for later use.\",\n \"Each different view created by the cloud service contains the data used to render a User Interface display for that view on a client computing device.\",\n \"Flowing to operation 450, aggregated content is delivered to a client using a single communication channel (e.g.\",\n \"a single delivery protocol).\",\n \"The client interacts with the aggregated data that is stored by cloud service using a single protocol even though cloud service used different protocols to obtain the aggregated content.\",\n \"According to an embodiment, the client is a thin client (e.g.\",\n \"a web browser) that uses the cloud service to perform computations and processing relating to the aggregated content.\",\n \"For example, the cloud service provides PIM services that are typically found in a desktop PIM application.\",\n \"The process flows to an end operation and returns to processing other actions.\",\n \"FIG.\",\n \"5 shows a process of a client interacting with a cloud service that stores aggregated content for the client.\",\n \"After a start operation, the process moves to operation 510, where the cloud service is accessed.\",\n \"The cloud service stores the aggregated content for a user.\",\n \"According to an embodiment, the aggregated content includes content relating to electronic messages, calendar information, and contacts obtained from different content sources.\",\n \"Other content may be aggregated.\",\n \"According to an embodiment, the cloud service provides services relating to interacting with and viewing electronic messages, calendar information, and contacts.\",\n \"Other cloud services may include other aggregated content and provide other services.\",\n \"Transitioning to operation 520, a user selects a view to display using their client application (e.g.\",\n \"browser, thin client).\",\n \"For example, a user may make a selection to display a: calendar view (e.g.\",\n \"yearly, monthly, weekly, daily); an electronic message, a contact; a task, and the like.\",\n \"Generally, the view is related to the functionality of the cloud service.\",\n \"Flowing to operation 530, the aggregated content relating to the view is obtained from the cloud service and the view is displayed at the client.\",\n \"According to an embodiment, the view is obtained from the cloud service.\",\n \"For example, when the view has already been created by the cloud service, the view is obtained from a memory (e.g.\",\n \"a cache or network storage) and delivered to the client for display.\",\n \"Transitioning to operation 540, a user interacts with the view.\",\n \"For example, a user may make changes to the view, change the content, create a message, create an event, and the like.\",\n \"A user may also perform a search across one or more of the different content sources that are included in the aggregated content.\",\n \"For example, a user may look for messages from particular user across each of their mailboxes, look for contacts obtained from different contact sources, and the like.\",\n \"Flowing to operation 550, changes made to the aggregated content are synchronized with the external content source.\",\n \"According to an embodiment, instead of just changing the content at the cloud service, the cloud service changes the content at the cloud service and synchronizes the change with the external content source.\",\n \"For example, if a user adds a calendar event to a calendar obtained from service provider 1, then the cloud service synchronizes the calendar that is stored by service provider 1.In this way, when a user accesses the calendar using an application supplied by service provider 1, the change to the calendar is shown.\",\n \"The process flows to an end operation and returns to processing other actions.\",\n \"FIG.\",\n \"6 illustrates an exemplary online system for aggregating content from different content sources.\",\n \"As illustrated, system 1000 includes service 1010, data store 1045, touch screen input device 1050 (e.g.\",\n \"a tablet/slate), smart phone 1030 and display device 1080.As illustrated, service 1010 is a cloud based and/or enterprise based service that may be configured to provide services, such as services related to various applications (e.g.\",\n \"whiteboards, searching, games, browsing, locating, productivity services (e.g.\",\n \"spreadsheets, documents, presentations, charts, messages, and the like)).\",\n \"The service may be interacted with using different types of input/output.\",\n \"For example, a user may use speech input, touch input, hardware based input, and the like.\",\n \"The service may provide speech output that combines pre-recorded speech and synthesized speech.\",\n \"Functionality of one or more of the services/applications provided by service 1010 may also be configured as a client/server based application.\",\n \"As illustrated, service 1010 is a multi-tenant service that provides resources 1015 and services to any number of tenants (e.g.\",\n \"Tenants 1-N).\",\n \"Multi-tenant service 1010 is a cloud based service that provides resources/services 1015 to tenants subscribed to the service and maintains each tenant's data separately and protected from other tenant data.\",\n \"System 1000 as illustrated comprises a touch screen input device 1050 (e.g.\",\n \"a slate/tablet device) and smart phone 1030 that detects when a touch input has been received (e.g.\",\n \"a finger touching or nearly touching the touch screen).\",\n \"Any type of touch screen may be utilized that detects a user's touch input.\",\n \"For example, the touch screen may include one or more layers of capacitive material that detects the touch input.\",\n \"Other sensors may be used in addition to or in place of the capacitive material.\",\n \"For example, Infrared (IR) sensors may be used.\",\n \"According to an embodiment, the touch screen is configured to detect objects that in contact with or above a touchable surface.\",\n \"Although the term “above” is used in this description, it should be understood that the orientation of the touch panel system is irrelevant.\",\n \"The term “above” is intended to be applicable to all such orientations.\",\n \"The touch screen may be configured to determine locations of where touch input is received (e.g.\",\n \"a starting point, intermediate points and an ending point).\",\n \"Actual contact between the touchable surface and the object may be detected by any suitable means, including, for example, by a vibration sensor or microphone coupled to the touch panel.\",\n \"A non-exhaustive list of examples for sensors to detect contact includes pressure-based mechanisms, micro-machined accelerometers, piezoelectric devices, capacitive sensors, resistive sensors, inductive sensors, laser vibrometers, and LED vibrometers.\",\n \"According to an embodiment, smart phone 1030, touch screen input device 1050, and device 1080 are configured with multimodal input/output and each include an application (1031, 1051, 1081).\",\n \"As illustrated, touch screen input device 1050, smart phone 1030, and display device 1080 shows exemplary displays 1052/1032/1082 showing the use of an application, such as an application that is accessing aggregated content that is associated with a user and stored by service 1010.Data may be stored on a device (e.g.\",\n \"smart phone 1030, touch screen input device 1050 and/or at some other location (e.g.\",\n \"network data store 1045).\",\n \"Data store 1045, or some other store, may be used to store aggregated content as well as other data.\",\n \"The applications used by the devices may be client based applications, server based applications, cloud based applications and/or some combination.\",\n \"According to an embodiment, display device 1080 is a device such as a MICROSOFT XBOX coupled to a display.\",\n \"Content manager 26 is configured to perform operations relating to aggregating content as described herein.\",\n \"The embodiments and functionalities described herein may operate via a multitude of computing systems including, without limitation, desktop computer systems, wired and wireless computing systems, mobile computing systems (e.g., mobile telephones, netbooks, tablet or slate type computers, notebook computers, and laptop computers), hand-held devices, multiprocessor systems, microprocessor-based or programmable consumer electronics, minicomputers, and mainframe computers.\",\n \"In addition, the embodiments and functionalities described herein may operate over distributed systems (e.g., cloud-based computing systems), where application functionality, memory, data storage and retrieval and various processing functions may be operated remotely from each other over a distributed computing network, such as the Internet or an intranet.\",\n \"User interfaces and information of various types may be displayed via on-board computing device displays or via remote display units associated with one or more computing devices.\",\n \"For example user interfaces and information of various types may be displayed and interacted with on a wall surface onto which user interfaces and information of various types are projected.\",\n \"Interaction with the multitude of computing systems with which embodiments of the invention may be practiced include, keystroke entry, touch screen entry, voice or other audio entry, gesture entry where an associated computing device is equipped with detection (e.g., camera) functionality for capturing and interpreting user gestures for controlling the functionality of the computing device, and the like.\",\n \"FIGS.\",\n \"7-9 and the associated descriptions provide a discussion of a variety of operating environments in which embodiments of the invention may be practiced.\",\n \"However, the devices and systems illustrated and discussed with respect to FIGS.\",\n \"7-9 are for purposes of example and illustration and are not limiting of a vast number of computing device configurations that may be utilized for practicing embodiments of the invention, described herein.\",\n \"FIG.\",\n \"7 is a block diagram illustrating physical components (i.e., hardware) of a computing device 1100 with which embodiments of the invention may be practiced.\",\n \"The computing device components described below may be suitable for the computing devices described above.\",\n \"In a basic configuration, the computing device 1100 may include at least one processing unit 1102 and a system memory 1104.Depending on the configuration and type of computing device, the system memory 1104 may comprise, but is not limited to, volatile storage (e.g., random access memory), non-volatile storage (e.g., read-only memory), flash memory, or any combination of such memories.\",\n \"The system memory 1104 may include an operating system 1105 and one or more program modules 1106 suitable for running software applications 1120 such as the content manager 26.The operating system 1105, for example, may be suitable for controlling the operation of the computing device 1100.Furthermore, embodiments of the invention may be practiced in conjunction with a graphics library, other operating systems, or any other application program and is not limited to any particular application or system.\",\n \"This basic configuration is illustrated in FIG.\",\n \"7 by those components within a dashed line 1108.The computing device 1100 may have additional features or functionality.\",\n \"For example, the computing device 1100 may also include additional data storage devices (removable and/or non-removable) such as, for example, magnetic disks, optical disks, or tape.\",\n \"Such additional storage is illustrated in FIG.\",\n \"7 by a removable storage device 1109 and a non-removable storage device 1110.As stated above, a number of program modules and data files may be stored in the system memory 1104.While executing on the processing unit 1102, the program modules 1106 (e.g., the content manager 26) may perform processes including, but not limited to, one or more of the stages of the methods and processes illustrated in the figures.\",\n \"Other program modules that may be used in accordance with embodiments of the present invention may include electronic mail and contacts applications, word processing applications, spreadsheet applications, database applications, slide presentation applications, drawing or computer-aided application programs, etc.\",\n \"Furthermore, embodiments of the invention may be practiced in an electrical circuit comprising discrete electronic elements, packaged or integrated electronic chips containing logic gates, a circuit utilizing a microprocessor, or on a single chip containing electronic elements or microprocessors.\",\n \"For example, embodiments of the invention may be practiced via a system-on-a-chip (SOC) where each or many of the components illustrated in FIG.\",\n \"7 may be integrated onto a single integrated circuit.\",\n \"Such an SOC device may include one or more processing units, graphics units, communications units, system virtualization units and various application functionality all of which are integrated (or “burned”) onto the chip substrate as a single integrated circuit.\",\n \"When operating via an SOC, the functionality, described herein, with respect to the content manager 26 may be operated via application-specific logic integrated with other components of the computing device 1100 on the single integrated circuit (chip).\",\n \"Embodiments of the invention may also be practiced using other technologies capable of performing logical operations such as, for example, AND, OR, and NOT, including but not limited to mechanical, optical, fluidic, and quantum technologies.\",\n \"In addition, embodiments of the invention may be practiced within a general purpose computer or in any other circuits or systems.\",\n \"The computing device 1100 may also have one or more input device(s) 1112 such as a keyboard, a mouse, a pen, a sound input device, a touch input device, etc.\",\n \"The output device(s) 1114 such as a display, speakers, a printer, etc.\",\n \"may also be included.\",\n \"The aforementioned devices are examples and others may be used.\",\n \"The computing device 1100 may include one or more communication connections 1116 allowing communications with other computing devices 1118.Examples of suitable communication connections 1116 include, but are not limited to, RF transmitter, receiver, and/or transceiver circuitry; universal serial bus (USB), parallel, and/or serial ports.\",\n \"The term computer readable media as used herein may include computer storage media.\",\n \"Computer storage media may include volatile and nonvolatile, removable and non-removable media implemented in any method or technology for storage of information, such as computer readable instructions, data structures, or program modules.\",\n \"The system memory 1104, the removable storage device 1109, and the non-removable storage device 1110 are all computer storage media examples (i.e., memory storage.)\",\n \"Computer storage media may include RAM, ROM, electrically erasable read-only memory (EEPROM), flash memory or other memory technology, CD-ROM, digital versatile disks (DVD) or other optical storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other article of manufacture which can be used to store information and which can be accessed by the computing device 1100.Any such computer storage media may be part of the computing device 1100.Computer storage media does not include a carrier wave or other propagated or modulated data signal.\",\n \"Communication media may be embodied by computer readable instructions, data structures, program modules, or other data in a modulated data signal, such as a carrier wave or other transport mechanism, and includes any information delivery media.\",\n \"The term “modulated data signal” may describe a signal that has one or more characteristics set or changed in such a manner as to encode information in the signal.\",\n \"By way of example, and not limitation, communication media may include wired media such as a wired network or direct-wired connection, and wireless media such as acoustic, radio frequency (RF), infrared, and other wireless media.\",\n \"FIGS.\",\n \"8A and 8B illustrate a mobile computing device 1200, for example, a mobile telephone, a smart phone, a tablet personal computer, a laptop computer, and the like, with which embodiments of the invention may be practiced.\",\n \"With reference to FIG.\",\n \"8A, one embodiment of a mobile computing device 1200 for implementing the embodiments is illustrated.\",\n \"In a basic configuration, the mobile computing device 1200 is a handheld computer having both input elements and output elements.\",\n \"The mobile computing device 1200 typically includes a display 1205 and one or more input buttons 1210 that allow the user to enter information into the mobile computing device 1200.The display 1205 of the mobile computing device 1200 may also function as an input device (e.g., a touch screen display).\",\n \"If included, an optional side input element 1215 allows further user input.\",\n \"The side input element 1215 may be a rotary switch, a button, or any other type of manual input element.\",\n \"In alternative embodiments, mobile computing device 1200 may incorporate more or less input elements.\",\n \"For example, the display 1205 may not be a touch screen in some embodiments.\",\n \"In yet another alternative embodiment, the mobile computing device 1200 is a portable phone system, such as a cellular phone.\",\n \"The mobile computing device 1200 may also include an optional keypad 1235.Optional keypad 1235 may be a physical keypad or a “soft” keypad generated on the touch screen display.\",\n \"In various embodiments, the output elements include the display 1205 for showing a graphical user interface (GUI), a visual indicator 1220 (e.g., a light emitting diode), and/or an audio transducer 1225 (e.g., a speaker).\",\n \"In some embodiments, the mobile computing device 1200 incorporates a vibration transducer for providing the user with tactile feedback.\",\n \"In yet another embodiment, the mobile computing device 1200 incorporates input and/or output ports, such as an audio input (e.g., a microphone jack), an audio output (e.g., a headphone jack), and a video output (e.g., a HDMI port) for sending signals to or receiving signals from an external device.\",\n \"FIG.\",\n \"8B is a block diagram illustrating the architecture of one embodiment of a mobile computing device.\",\n \"That is, the mobile computing device 1200 can incorporate a system 1202 (i.e., an architecture) to implement some embodiments.\",\n \"In one embodiment, the system 1202 is implemented as a “smart phone” capable of running one or more applications (e.g., browser, e-mail, calendaring, contact managers, messaging clients, games, and media clients/players).\",\n \"In some embodiments, the system 1202 is integrated as a computing device, such as an integrated personal digital assistant (PDA) and wireless phone.\",\n \"One or more application programs 1266 may be loaded into the memory 1262 and run on or in association with the operating system 1264.Examples of the application programs include phone dialer programs, e-mail programs, personal information management (PIM) programs, word processing programs, spreadsheet programs, Internet browser programs, messaging programs, and so forth.\",\n \"The system 1202 also includes a non-volatile storage area 1268 within the memory 1262.The non-volatile storage area 1268 may be used to store persistent information that should not be lost if the system 1202 is powered down.\",\n \"The application programs 1266 may use and store information in the non-volatile storage area 1268, such as e-mail or other messages used by an e-mail application, and the like.\",\n \"A synchronization application (not shown) also resides on the system 1202 and is programmed to interact with a corresponding synchronization application resident on a host computer to keep the information stored in the non-volatile storage area 1268 synchronized with corresponding information stored at the host computer.\",\n \"As should be appreciated, other applications may be loaded into the memory 1262 and run on the mobile computing device 1200, including the content manager 26 as described herein.\",\n \"The system 1202 has a power supply 1270, which may be implemented as one or more batteries.\",\n \"The power supply 1270 might further include an external power source, such as an AC adapter or a powered docking cradle that supplements or recharges the batteries.\",\n \"The system 1202 may also include a radio 1272 that performs the function of transmitting and receiving radio frequency communications.\",\n \"The radio 1272 facilitates wireless connectivity between the system 1202 and the “outside world,” via a communications carrier or service provider.\",\n \"Transmissions to and from the radio 1272 are conducted under control of the operating system 1264.In other words, communications received by the radio 1272 may be disseminated to the application programs 1266 via the operating system 1264, and vice versa.\",\n \"The visual indicator 1220 may be used to provide visual notifications, and/or an audio interface 1274 may be used for producing audible notifications via the audio transducer 1225.In the illustrated embodiment, the visual indicator 1220 is a light emitting diode (LED) and the audio transducer 1225 is a speaker.\",\n \"These devices may be directly coupled to the power supply 1270 so that when activated, they remain on for a duration dictated by the notification mechanism even though the processor 1260 and other components might shut down for conserving battery power.\",\n \"The LED may be programmed to remain on indefinitely until the user takes action to indicate the powered-on status of the device.\",\n \"The audio interface 1274 is used to provide audible signals to and receive audible signals from the user.\",\n \"For example, in addition to being coupled to the audio transducer 1225, the audio interface 1274 may also be coupled to a microphone to receive audible input, such as to facilitate a telephone conversation.\",\n \"In accordance with embodiments of the present invention, the microphone may also serve as an audio sensor to facilitate control of notifications, as will be described below.\",\n \"The system 1202 may further include a video interface 1276 that enables an operation of an on-board camera to record still images, video stream, and the like.\",\n \"A mobile computing device 1200 implementing the system 1202 may have additional features or functionality.\",\n \"For example, the mobile computing device 1200 may also include additional data storage devices (removable and/or non-removable) such as, magnetic disks, optical disks, or tape.\",\n \"Such additional storage is illustrated in FIG.\",\n \"8B by the non-volatile storage area 1268.Mobile computing device 1200 may also include peripheral device port 1230.Data/information generated or captured by the mobile computing device 1200 and stored via the system 1202 may be stored locally on the mobile computing device 1200, as described above, or the data may be stored on any number of storage media that may be accessed by the device via the radio 1272 or via a wired connection between the mobile computing device 1200 and a separate computing device associated with the mobile computing device 1200, for example, a server computer in a distributed computing network, such as the Internet.\",\n \"As should be appreciated such data/information may be accessed via the mobile computing device 1200 via the radio 1272 or via a distributed computing network.\",\n \"Similarly, such data/information may be readily transferred between computing devices for storage and use according to well-known data/information transfer and storage means, including electronic mail and collaborative data/information sharing systems.\",\n \"FIG.\",\n \"9 illustrates an embodiment of an architecture of an exemplary system, as described above.\",\n \"Content developed, interacted with, or edited in association with the content manager 26 may be stored in different communication channels or other storage types.\",\n \"For example, various documents may be stored using a directory service 1322, a web portal 1324, a mailbox service 1326, an instant messaging store 1328, or a social networking site 1330.The content manager 26 may use any of these types of systems or the like for enabling data utilization, as described herein.\",\n \"A server 1320 may provide the content manager 26 to clients.\",\n \"As one example, the server 1320 may be a web server providing the content manager 26 over the web.\",\n \"The server 1320 may provide the content manager 26 over the web to clients through a network 1315.By way of example, the client computing device may be implemented as the computing device 1100 and embodied in a personal computer, a tablet computing device 1310 and/or a mobile computing device 1200 (e.g., a smart phone).\",\n \"Any of these embodiments of the client computing device 1100, 1310, and 1200 may obtain content from the store 1316.Embodiments of the present invention, for example, are described above with reference to block diagrams and/or operational illustrations of methods, systems, and computer program products according to embodiments of the invention.\",\n \"The functions/acts noted in the blocks may occur out of the order as shown in any flowchart.\",\n \"For example, two blocks shown in succession may in fact be executed substantially concurrently or the blocks may sometimes be executed in the reverse order, depending upon the functionality/acts involved.\",\n \"The description and illustration of one or more embodiments provided in this application are not intended to limit or restrict the scope of the invention as claimed in any way.\",\n \"The embodiments, examples, and details provided in this application are considered sufficient to convey possession and enable others to make and use the best mode of claimed invention.\",\n \"The claimed invention should not be construed as being limited to any embodiment, example, or detail provided in this application.\",\n \"Regardless of whether shown and described in combination or separately, the various features (both structural and methodological) are intended to be selectively included or omitted to produce an embodiment with a particular set of features.\",\n \"Having been provided with the description and illustration of the present application, one skilled in the art may envision variations, modifications, and alternate embodiments falling within the spirit of the broader aspects of the general inventive concept embodied in this application that do not depart from the broader scope of the claimed invention.\"\n ]\n]"},"source":{"kind":"string","value":"Patent_15872014"}}},{"rowIdx":4493983,"cells":{"text":{"kind":"list like","value":[["BIASING OF ELECTROMECHANICAL SYSTEMS TRANSDUCER WITH ALTERNATING-CURRENT VOLTAGE WAVEFORM","A MEMS microphone may include a backplate comprising first and second electrodes electrically isolated from one another and mechanically coupled to the backplate in a fixed relationship relative to the backplate and a diaphragm configured to displace relative to the backplate as a function of sound pressure incident upon the diaphragm, the diaphragm comprising third and fourth electrodes electrically isolated from one another and mechanically coupled to the diaphragm in a fixed relationship relative to the diaphragm such that the third and fourth electrodes displace relative to the backplate as a function of sound pressure incident upon the diaphragm.","The first and third electrodes may form a first capacitor and the second and fourth electrodes may form a second capacitor, the capacitance of each which may be a function of the displacement of the diaphragm, and each of which may be biased by an alternating-current voltage waveform."],["1.A microelectromechanical systems transducer, comprising: a backplate comprising a first plurality of electrodes comprising at least a first electrode and a second electrode electrically isolated from one another and each is mechanically coupled to the backplate in a fixed relationship relative to the backplate; and a diaphragm configured to mechanically displace relative to the backplate as a function of pressure incident upon the diaphragm, wherein the diaphragm comprises a second plurality of electrodes, the second plurality of electrodes comprising at least a third electrode and a fourth electrode, wherein the third electrode and the fourth electrode are electrically isolated from one another and each is mechanically coupled to the diaphragm in a fixed relationship relative to the diaphragm such that the second plurality of electrodes mechanically displace relative to the backplate as the function of pressure incident upon the diaphragm; wherein: the first electrode and the third electrode form a first capacitor having a first capacitance which is a function of a displacement of the diaphragm relative to the backplate; the second electrode and the fourth electrode form a second capacitor having a second capacitance which is a function of the displacement of the diaphragm relative to the backplate; and each of the first capacitor and the second capacitor are biased by an alternating-current voltage waveform; wherein the first electrode is electrically coupled to a first terminal of a voltage supply providing the alternating-current voltage waveform and the second electrode is electrically coupled to a second terminal of the voltage supply.","2.","(canceled) 3.The microelectromechanical systems transducer of claim 1, wherein the first capacitor and the second capacitor are electrically coupled to one another in a bridge structure, the bridge structure comprising: a third capacitor in series with the first capacitor and coupled between the first capacitor and the second terminal of the voltage supply; and a fourth capacitor in series with the second capacitor and coupled between the second capacitor and the first terminal of the voltage supply.","4.The microelectromechanical systems transducer of claim 3, further comprising a direct-current voltage detector configured to detect a direct-current voltage offset present in the bridge structure.","5.The microelectromechanical systems transducer of claim 4, wherein the direct-current voltage detector is further configured to control at least one of a third capacitance of the third capacitor and a fourth capacitance of the fourth capacitor responsive to the direct-current voltage offset.","6.The microelectromechanical systems transducer of claim 1, wherein the alternating-current voltage waveform has a frequency greater than that of human hearing.","7.The microelectromechanical systems transducer of claim 1, wherein a magnitude of the alternating-current voltage waveform is set based on a magnitude of pressure upon the diaphragm in order to maximize a dynamic range of the microelectromechanical systems microphone.","8.The microelectromechanical systems transducer of claim 7, wherein the magnitude of the alternating-current voltage waveform increases as the pressure upon the diaphragm decreases and vice versa.","9.The microelectromechanical systems transducer of claim 1, further comprising a capacitance detector configured to measure at least one of the first capacitance and the second capacitance.","10.The microelectromechanical systems transducer of claim 9, wherein the capacitance detector is further configured to control a gain of the microelectromechanical systems microphone responsive to the measurement of at least one of the first capacitance and the second capacitance.","11.A method, comprising: biasing a first capacitor of an electromechanical systems transducer with an alternating-current voltage waveform; biasing a second capacitor of the electromechanical systems transducer with the alternating-current voltage waveform; wherein: the first capacitor is formed from a first electrode and a third electrode; the second capacitor is formed from a second electrode and a fourth electrode; the first electrode and the second electrode are electrically isolated from one another and each is mechanically coupled to a backplate in a fixed relationship relative to the backplate, the backplate comprising a first plurality of electrodes comprising the first electrode and the second electrode; the third electrode and the fourth electrode are electrically isolated from one another and each is mechanically coupled to a diaphragm in a fixed relationship relative to the diaphragm such that the second plurality of electrodes mechanically displace relative to the backplate as the function of pressure incident upon the diaphragm which mechanically displaces the diaphragm relative to the backplate; the first capacitor has a first capacitance which is a function of a displacement of the diaphragm relative to the backplate; and the second capacitor has a second capacitance which is a function of a displacement of the diaphragm relative to the backplate; and electrically coupling the first electrode to a first terminal of a voltage supply providing the alternating-current voltage waveform and electrically coupling the second electrode to a second terminal of the voltage supply.","12.","(canceled) 13.The method of claim 11, wherein the first capacitor and the second capacitor are electrically coupled to one another in a bridge structure, the bridge structure comprising: a third capacitor in series with the first capacitor and coupled between the first capacitor and the second terminal of the voltage supply; and a fourth capacitor in series with the second capacitor and coupled between the second capacitor and the first terminal of the voltage supply.","14.The method of claim 13, further comprising detecting a direct-current voltage offset present in the bridge structure.","15.The method of claim 14, further comprising controlling at least one of a third capacitance of the third capacitor and a fourth capacitance of the fourth capacitor responsive to the direct-current voltage offset.","16.The method of claim 11, wherein the alternating-current voltage waveform has a frequency greater than that of human hearing.","17.The method of claim 11, further comprising setting a magnitude of the alternating-current voltage waveform based on a magnitude of pressure upon the diaphragm in order to maximize a dynamic range of the microelectromechanical systems transducer.","18.The method of claim 17, further comprising increasing the magnitude of the alternating-current voltage waveform as the pressure upon the diaphragm decreases and vice versa.","19.The method of claim 11, further comprising measuring at least one of the first capacitance and the second capacitance.","20.The method of claim 19, further comprising controlling a gain of the microelectromechanical systems transducer responsive to the measurement of at least one of the first capacitance and the second capacitance."],[" BACKGROUND Microphones are ubiquitous on many devices used by individuals, including computers, tablets, smart phones, and many other consumer devices.","Generally speaking, a microphone is an electroacoustic transducer that produces an electrical signal in response to deflection of a portion (e.g., a membrane or other structure) of a microphone caused by sound incident upon the microphone.","For example, a microphone may be implemented as a MEMS transducer.","A MEMS transducer may include a diaphragm or membrane having an electrical capacitance to a reference plane or backplate, such that a change in acoustic pressure applied to the MEMS transducer causes a deflection or other movement of the membrane, and thus causes a change in the electrical capacitance.","Such electrical capacitance or the change thereof may be sensed by a sensing circuit and processed.","Existing MEMS microphone implementations are susceptible to a variety of electronic noise sources that may negatively affect a signal-to-noise ratio of a MEMS microphone.","Among such noise sources are flicker noise (also known as 1/f noise) and noise bias resistors used in the biasing topology of existing approaches.","Also, as with any audio system, it may be desirable to improve dynamic range of MEMS microphone implementations compared to that of existing implementations."],[" SUMMARY In accordance with the teachings of the present disclosure, certain disadvantages and problems associated with existing MEMS transducers may be reduced or eliminated.","In accordance with embodiments of the present disclosure, a microelectromechanical systems microphone may include a backplate comprising a first plurality of electrodes comprising at least a first electrode and a second electrode electrically isolated from one another and each are mechanically coupled to the backplate in a fixed relationship relative to the backplate, and a diaphragm configured to mechanically displace relative to the backplate as a function of sound pressure incident upon the diaphragm, wherein the diaphragm comprises a second plurality of electrodes, the second plurality of electrodes comprising at least a third electrode and a fourth electrode, wherein the third electrode and the fourth electrode are electrically isolated from one another and each is mechanically coupled to the diaphragm in a fixed relationship relative to the diaphragm such that the second plurality of electrodes mechanically displace relative to the backplate as the function of sound pressure incident upon the diaphragm.","The first electrode and the third electrode may form a first capacitor having a first capacitance which is a function of a displacement of the diaphragm relative to the backplate.","The second electrode and the fourth electrode may form a second capacitor having a second capacitance which is a function of the displacement of the diaphragm relative to the backplate.","Each of the first capacitor and the second capacitor may be biased by an alternating-current voltage waveform.","In accordance with these and other embodiments of the present disclosure, a method may include biasing a first capacitor of an electromechanical systems microphone with an alternating-current voltage waveform and biasing a second capacitor of the electromechanical systems microphone with the alternating-current voltage waveform.","The first capacitor may be formed from a first electrode and a third electrode and the second capacitor may be formed from a second electrode and a fourth electrode.","The first electrode and the second electrode may be electrically isolated from one another and may each be mechanically coupled to a backplate in a fixed relationship relative to the backplate, the backplate comprising a first plurality of electrodes comprising the first electrode and the second electrode.","The third electrode and the fourth electrode may be electrically isolated from one another and may each be mechanically coupled to a diaphragm in a fixed relationship relative to the diaphragm such that the second plurality of electrodes mechanically displace relative to the backplate as the function of sound pressure incident upon the diaphragm which mechanically displaces the diaphragm relative to the backplate.","The first capacitor may have a first capacitance which is a function of a displacement of the diaphragm relative to the backplate and the second capacitor may have a second capacitance which is a function of a displacement of the diaphragm relative to the backplate.","Technical advantages of the present disclosure may be readily apparent to one having ordinary skill in the art from the figures, description and claims included herein.","The objects and advantages of the embodiments will be realized and achieved at least by the elements, features, and combinations particularly pointed out in the claims.","It is to be understood that both the foregoing general description and the following detailed description are explanatory examples and are not restrictive of the claims set forth in this disclosure."],["RELATED APPLICATIONS The present disclosure is related to U.S.","Provisional Patent Application Ser.","No.","62/438,144, filed Dec. 22, 2016, which is incorporated by reference herein in its entirety.","FIELD OF DISCLOSURE The present disclosure relates in general to audio systems, and more particularly, to improving the performance of microelectromechanical systems (MEMS) based transducers as compared to traditional approaches.","BACKGROUND Microphones are ubiquitous on many devices used by individuals, including computers, tablets, smart phones, and many other consumer devices.","Generally speaking, a microphone is an electroacoustic transducer that produces an electrical signal in response to deflection of a portion (e.g., a membrane or other structure) of a microphone caused by sound incident upon the microphone.","For example, a microphone may be implemented as a MEMS transducer.","A MEMS transducer may include a diaphragm or membrane having an electrical capacitance to a reference plane or backplate, such that a change in acoustic pressure applied to the MEMS transducer causes a deflection or other movement of the membrane, and thus causes a change in the electrical capacitance.","Such electrical capacitance or the change thereof may be sensed by a sensing circuit and processed.","Existing MEMS microphone implementations are susceptible to a variety of electronic noise sources that may negatively affect a signal-to-noise ratio of a MEMS microphone.","Among such noise sources are flicker noise (also known as 1/f noise) and noise bias resistors used in the biasing topology of existing approaches.","Also, as with any audio system, it may be desirable to improve dynamic range of MEMS microphone implementations compared to that of existing implementations.","SUMMARY In accordance with the teachings of the present disclosure, certain disadvantages and problems associated with existing MEMS transducers may be reduced or eliminated.","In accordance with embodiments of the present disclosure, a microelectromechanical systems microphone may include a backplate comprising a first plurality of electrodes comprising at least a first electrode and a second electrode electrically isolated from one another and each are mechanically coupled to the backplate in a fixed relationship relative to the backplate, and a diaphragm configured to mechanically displace relative to the backplate as a function of sound pressure incident upon the diaphragm, wherein the diaphragm comprises a second plurality of electrodes, the second plurality of electrodes comprising at least a third electrode and a fourth electrode, wherein the third electrode and the fourth electrode are electrically isolated from one another and each is mechanically coupled to the diaphragm in a fixed relationship relative to the diaphragm such that the second plurality of electrodes mechanically displace relative to the backplate as the function of sound pressure incident upon the diaphragm.","The first electrode and the third electrode may form a first capacitor having a first capacitance which is a function of a displacement of the diaphragm relative to the backplate.","The second electrode and the fourth electrode may form a second capacitor having a second capacitance which is a function of the displacement of the diaphragm relative to the backplate.","Each of the first capacitor and the second capacitor may be biased by an alternating-current voltage waveform.","In accordance with these and other embodiments of the present disclosure, a method may include biasing a first capacitor of an electromechanical systems microphone with an alternating-current voltage waveform and biasing a second capacitor of the electromechanical systems microphone with the alternating-current voltage waveform.","The first capacitor may be formed from a first electrode and a third electrode and the second capacitor may be formed from a second electrode and a fourth electrode.","The first electrode and the second electrode may be electrically isolated from one another and may each be mechanically coupled to a backplate in a fixed relationship relative to the backplate, the backplate comprising a first plurality of electrodes comprising the first electrode and the second electrode.","The third electrode and the fourth electrode may be electrically isolated from one another and may each be mechanically coupled to a diaphragm in a fixed relationship relative to the diaphragm such that the second plurality of electrodes mechanically displace relative to the backplate as the function of sound pressure incident upon the diaphragm which mechanically displaces the diaphragm relative to the backplate.","The first capacitor may have a first capacitance which is a function of a displacement of the diaphragm relative to the backplate and the second capacitor may have a second capacitance which is a function of a displacement of the diaphragm relative to the backplate.","Technical advantages of the present disclosure may be readily apparent to one having ordinary skill in the art from the figures, description and claims included herein.","The objects and advantages of the embodiments will be realized and achieved at least by the elements, features, and combinations particularly pointed out in the claims.","It is to be understood that both the foregoing general description and the following detailed description are explanatory examples and are not restrictive of the claims set forth in this disclosure.","BRIEF DESCRIPTION OF THE DRAWINGS A more complete understanding of the present embodiments and advantages thereof may be acquired by referring to the following description taken in conjunction with the accompanying drawings, in which like reference numbers indicate like features, and wherein: FIG.","1 illustrates a block diagram of selected components of an example MEMS microphone, in accordance with embodiments of the present disclosure; and FIG.","2 illustrates a block diagram of selected components of an example audio system comprising a MEMS microphone biased with an alternating-current voltage waveform, in accordance with embodiments of the present disclosure.","DETAILED DESCRIPTION FIG.","1 illustrates a block diagram of selected components of an example MEMS microphone 100, in accordance with embodiments of the present disclosure.","As shown in FIG.","1, MEMS microphone 100 may comprise a backplate 102, a diaphragm 108, and a substrate 114.Backplate 102 may include a plurality of electrodes comprising at least a first electrode 104 and a second electrode 106 electrically isolated from one another and each mechanically coupled to backplate 102 in a fixed relationship relative to backplate 102.For the purposes of clarity and exposition, only two electrodes 104 and 106 are depicted in FIG.","1.In some embodiments, backplate 102 may include more than two electrodes.","Diaphragm 108 may comprise a membrane or other structure configured to mechanically displace relative to the backplate as a function of sound pressure incident upon diaphragm (e.g., through acoustic port 118 of substrate 114).","As shown in FIG.","1, backplate 102 may be mechanically coupled to diaphragm 108 via a plurality of support posts 116 of backplate 102.Diaphragm 108 may include a plurality of electrodes comprising at least a third electrode 110 and a fourth electrode 112, in which third electrode 110 and fourth electrode 112 are electrically isolated from one another and each is mechanically coupled to diaphragm 108 in a fixed relationship relative to diaphragm 108 such that electrodes 110 and 112 mechanically displace relative to backplate 102 as the function of sound pressure incident upon diaphragm 108.Substrate 114 may comprise any suitable substrate or surface (e.g., a semiconductor substrate) upon which MEMS microphone 100 may be fabricated.","The various components of MEMS microphone 100 (e.g., backplate 102, electrode 104, electrode 106, diaphragm 108, electrode 110, electrode 112, support posts 116, etc.)","may be formed on substrate using semiconductor fabrication techniques now known or semiconductor fabrication techniques that may be known in the future.","As also shown in FIG.","1, substrate 114 may also have an acoustic port 118 formed therein (e.g., using semiconductor fabrication techniques now known or semiconductor fabrication techniques that may be known in the future) through which sound pressure may propagate to diaphragm 108 to displace diaphragm 108 as a function of such sound pressure.","MEMS microphone 100 may be constructed such that first electrode 104 and third electrode 110 electrically interact with one another so as to form a first capacitor having a first capacitance which is a function of a displacement of diaphragm 108 relative to backplate 102.Similarly, MEMS microphone 100 may be constructed such that second electrode 106 and fourth electrode 112 electrically interact with one another so as to form a second capacitor having a second capacitance which is a function of a displacement of diaphragm 108 relative to backplate 102.The implementation shown in FIG.","1 may be one of many ways to construct a MEMS microphone in accordance with the present disclosure.","Accordingly, one or more other implementations may exist for a MEMS microphone which are substantially equivalent to that of MEMS microphone 100 depicted in FIG.","1.FIG.","2 illustrates a block diagram of selected components of an example audio system 200 comprising a MEMS microphone biased with an alternating-current voltage waveform, in accordance with embodiments of the present disclosure.","As shown in FIG.","2, audio system 200 may comprise a voltage supply 202, first capacitor 204 formed from first electrode 104 and third electrode 110, second capacitor 206 formed from second electrode 106 and fourth electrode 112, a third capacitor 208, a fourth capacitor 210, an amplifier 212, a demodulator 214, an analog-to-digital converter (ADC) 216, a direct-current voltage detector 218, a peak detector 220, a dynamic range enhancement controller 222, a capacitance measurement subsystem 224, a gain controller 226, and a gain element 228.Voltage supply 202 may comprise any suitable system, device, or apparatus configured to output an alternating-current (AC) bias voltage VBIAS for biasing first capacitor 204 and second capacitor 206, as described in greater detail below.","In some embodiments, voltage supply 202 may generate AC bias voltage VBIAS as a square-wave voltage waveform.","However, any suitable AC waveform may be used.","Voltage supply 202 may be implemented in any suitable manner, including without limitation with a charge pump power supply.","In some embodiments, AC bias voltage VBIAS may have a frequency greater than that of human hearing (e.g., greater than 20 kilohertz).","As shown in FIG.","2, first electrode 104 of first capacitor 204 may be electrically coupled to a first terminal of voltage supply 202 and second electrode 106 of second capacitor 206 may be electrically coupled to a second terminal of voltage supply 202.Accordingly, each of first capacitor 204 and second capacitor 206 may be biased by the alternating-current voltage waveform generated by voltage supply 202.Furthermore, as shown in FIG.","2, first capacitor 204 and second capacitor 206 may be electrically coupled to one another in a bridge structure, the bridge structure comprising third capacitor 208 in series with first capacitor 204 and coupled between first capacitor 204 and the second terminal of voltage supply 202 and fourth capacitor 210 in series with second capacitor 206 and coupled between second capacitor 206 and the first terminal of voltage supply 202.In operation, a differential signal VCAP comprising the difference in potential between a third electrode 110 and fourth electrode 112 may be generated due to the presence of AC bias voltage VBIAS and sound pressure incident on diaphragm 108 which induces changes in capacitances of first capacitor 204 and second capacitor 206.Thus, differential signal VCAP may comprise an audio signal which is a function of the sound pressure incident on diaphragm 108, wherein such audio signal is modulated at a frequency of AC bias voltage VBIAS.","Amplifier 212 may comprise any suitable system, device, or apparatus configured to amplify an analog signal received at its input (e.g., differential signal VCAP) to an amplified version of the input analog signal which may be more suitable for downstream processing.","Demodulator 214 may comprise any suitable system, device, or apparatus configured to extract from an analog signal (e.g., differential signal VCAP as amplified by amplifier 212) an information-bearing signal (e.g., analog microphone signal VMIC) from a modulated carrier wave (e.g., a modulated carrier wave at the frequency of AC bias voltage VBIAS).","In some embodiments, demodulator 214 may comprise a synchronous modulator.","ADC 216 may comprise any suitable system, device, or apparatus configured to convert an analog signal (e.g., analog microphone signal VMIC) into a corresponding digital signal (e.g., digital microphone signal MIC_DIG).","Direct-current voltage detector 218 may comprise any suitable system, device, or apparatus configured to receive digital microphone signal MIC_DIG and analyze such signal in order to detect a direct-current voltage offset present in differential signal VCAP of the bridge structure comprising capacitors 204, 206, 208, and 210.Based on the detected direct-current voltage offset present in differential signal VCAP, direct-current voltage detector 218 may generate a direct-current compensation control signal DC_COMP to control at least one of the third capacitance of third capacitor 208 and the fourth capacitance of fourth capacitor 210 responsive to the direct-current voltage offset in order to compensate for the presence of the direct-current voltage offset.","Peak detector 220 may include any suitable system, device, or apparatus configured to receive analog microphone signal VMIC (or a derivative thereof), determine a magnitude of such signal, and output a peak amplitude signal PEAK indicative of such magnitude.","Dynamic range enhancement controller 222 may include any suitable system, device, or apparatus configured to receive peak amplitude signal PEAK and based thereon, determine an analog gain for audio system 200 and generate an analog gain signal ANALOG_GAIN indicative of such analog gain.","Analog gain signal ANALOG_GAIN may be used as a control signal in order to set a magnitude of AC bias voltage VBIAS.","Accordingly, the magnitude of AC bias voltage VBIAS may be set based on the magnitude of sound pressure upon diaphragm 108 in order to maximize a dynamic range of microelectromechanical systems microphone 100 and audio system 200.For example, to maximize dynamic range, dynamic range enhancement controller 222 may cause the magnitude of AC bias voltage VBIAS to increase as the sound pressure upon diaphragm 108 decreases, and cause the magnitude of AC bias voltage VBIAS to decrease as the sound pressure upon diaphragm 108 increases.","Capacitance measurement subsystem 224 may include any suitable system, device, or apparatus configured to measure a capacitance of first capacitor 204 (as explicitly shown in FIG.","2) and/or second capacitor 206 and output a gain compensation signal GAIN_COMP indicative of such measured capacitance.","Such capacitance may be indicative of the sensitivity of measurement of audio system 200, and thus, as described below, may be used to compensate for such sensitivity.","Gain controller 226 may include any suitable system, device, or apparatus configured to receive analog gain signal ANALOG_GAIN and/or gain compensation signal GAIN_COMP and based thereon, generate a digital gain signal DIG_GAIN, which may be used by gain element 228 to control a digital gain applied to digital microphone signal MIC_DIG to generate an audio output signal AUDIO_OUT of audio system 200.Accordingly, digital gain signal DIG_GAIN may include two components.","First, the level of digital gain indicated by digital gain signal DIG_GAIN may be based on an inverse of analog gain indicated by analog gain signal ANALOG_GAIN, in order to offset the analog gain applied in audio system 200 (e.g., to voltage supply 202) to maximize dynamic range.","Second, the level of digital gain indicated by digital gain signal DIG_GAIN may also control a gain of audio system 200 responsive to the sensitivity of measurement, as may be indicated by the first capacitance of capacitor 204 and/or the second capacitance of capacitor 206.Advantageously, the systems and methods herein may provide an improvement over existing MEMS microphone implementations.","For example, replacing the direct-current (DC) biasing present in existing approaches with the AC biasing approach of the systems and methods disclosed herein creates a signal of interest modulated by a frequency of AC bias voltage VBIAS, reducing or eliminating flicker noise and/or bias resistor noise that is typically present at low frequencies or at DC.","In addition, because of the symmetric excitation applied to the capacitor bridge of audio system 200, the magnitude of AC bias voltage VBIAS may be modified without disturbing a bias point of the sensing amplifier (e.g., amplifier 212) of audio system 200.Accordingly, such magnitude of AC bias voltage VBIAS may be modified as a function of the magnitude of the acoustic pressure incident upon MEMS microphone 100, thus maximizing the dynamic range of MEMS microphone 100 and audio system 200.Furthermore, unlike DC-biased implementations, in which only the change in capacitance of MEMS microphone 100 can be measured but not the static capacitance, in the systems and methods described herein, such static capacitance can be measured, allowing for collection of additional information regarding audio system 200 (e.g., sensitivity), for which audio system 200 may make further adjustments to improve accuracy.","This disclosure encompasses all changes, substitutions, variations, alterations, and modifications to the example embodiments herein that a person having ordinary skill in the art would comprehend.","Similarly, where appropriate, the appended claims encompass all changes, substitutions, variations, alterations, and modifications to the example embodiments herein that a person having ordinary skill in the art would comprehend.","Moreover, reference in the appended claims to an apparatus or system or a component of an apparatus or system being adapted to, arranged to, capable of, configured to, enabled to, operable to, or operative to perform a particular function encompasses that apparatus, system, or component, whether or not it or that particular function is activated, turned on, or unlocked, as long as that apparatus, system, or component is so adapted, arranged, capable, configured, enabled, operable, or operative.","All examples and conditional language recited herein are intended for pedagogical objects to aid the reader in understanding the disclosure and the concepts contributed by the inventor to furthering the art, and are construed as being without limitation to such specifically recited examples and conditions.","Although embodiments of the present disclosure have been described in detail, it should be understood that various changes, substitutions, and alterations could be made hereto without departing from the spirit and scope of the disclosure."]],"string":"[\n [\n \"BIASING OF ELECTROMECHANICAL SYSTEMS TRANSDUCER WITH ALTERNATING-CURRENT VOLTAGE WAVEFORM\",\n \"A MEMS microphone may include a backplate comprising first and second electrodes electrically isolated from one another and mechanically coupled to the backplate in a fixed relationship relative to the backplate and a diaphragm configured to displace relative to the backplate as a function of sound pressure incident upon the diaphragm, the diaphragm comprising third and fourth electrodes electrically isolated from one another and mechanically coupled to the diaphragm in a fixed relationship relative to the diaphragm such that the third and fourth electrodes displace relative to the backplate as a function of sound pressure incident upon the diaphragm.\",\n \"The first and third electrodes may form a first capacitor and the second and fourth electrodes may form a second capacitor, the capacitance of each which may be a function of the displacement of the diaphragm, and each of which may be biased by an alternating-current voltage waveform.\"\n ],\n [\n \"1.A microelectromechanical systems transducer, comprising: a backplate comprising a first plurality of electrodes comprising at least a first electrode and a second electrode electrically isolated from one another and each is mechanically coupled to the backplate in a fixed relationship relative to the backplate; and a diaphragm configured to mechanically displace relative to the backplate as a function of pressure incident upon the diaphragm, wherein the diaphragm comprises a second plurality of electrodes, the second plurality of electrodes comprising at least a third electrode and a fourth electrode, wherein the third electrode and the fourth electrode are electrically isolated from one another and each is mechanically coupled to the diaphragm in a fixed relationship relative to the diaphragm such that the second plurality of electrodes mechanically displace relative to the backplate as the function of pressure incident upon the diaphragm; wherein: the first electrode and the third electrode form a first capacitor having a first capacitance which is a function of a displacement of the diaphragm relative to the backplate; the second electrode and the fourth electrode form a second capacitor having a second capacitance which is a function of the displacement of the diaphragm relative to the backplate; and each of the first capacitor and the second capacitor are biased by an alternating-current voltage waveform; wherein the first electrode is electrically coupled to a first terminal of a voltage supply providing the alternating-current voltage waveform and the second electrode is electrically coupled to a second terminal of the voltage supply.\",\n \"2.\",\n \"(canceled) 3.The microelectromechanical systems transducer of claim 1, wherein the first capacitor and the second capacitor are electrically coupled to one another in a bridge structure, the bridge structure comprising: a third capacitor in series with the first capacitor and coupled between the first capacitor and the second terminal of the voltage supply; and a fourth capacitor in series with the second capacitor and coupled between the second capacitor and the first terminal of the voltage supply.\",\n \"4.The microelectromechanical systems transducer of claim 3, further comprising a direct-current voltage detector configured to detect a direct-current voltage offset present in the bridge structure.\",\n \"5.The microelectromechanical systems transducer of claim 4, wherein the direct-current voltage detector is further configured to control at least one of a third capacitance of the third capacitor and a fourth capacitance of the fourth capacitor responsive to the direct-current voltage offset.\",\n \"6.The microelectromechanical systems transducer of claim 1, wherein the alternating-current voltage waveform has a frequency greater than that of human hearing.\",\n \"7.The microelectromechanical systems transducer of claim 1, wherein a magnitude of the alternating-current voltage waveform is set based on a magnitude of pressure upon the diaphragm in order to maximize a dynamic range of the microelectromechanical systems microphone.\",\n \"8.The microelectromechanical systems transducer of claim 7, wherein the magnitude of the alternating-current voltage waveform increases as the pressure upon the diaphragm decreases and vice versa.\",\n \"9.The microelectromechanical systems transducer of claim 1, further comprising a capacitance detector configured to measure at least one of the first capacitance and the second capacitance.\",\n \"10.The microelectromechanical systems transducer of claim 9, wherein the capacitance detector is further configured to control a gain of the microelectromechanical systems microphone responsive to the measurement of at least one of the first capacitance and the second capacitance.\",\n \"11.A method, comprising: biasing a first capacitor of an electromechanical systems transducer with an alternating-current voltage waveform; biasing a second capacitor of the electromechanical systems transducer with the alternating-current voltage waveform; wherein: the first capacitor is formed from a first electrode and a third electrode; the second capacitor is formed from a second electrode and a fourth electrode; the first electrode and the second electrode are electrically isolated from one another and each is mechanically coupled to a backplate in a fixed relationship relative to the backplate, the backplate comprising a first plurality of electrodes comprising the first electrode and the second electrode; the third electrode and the fourth electrode are electrically isolated from one another and each is mechanically coupled to a diaphragm in a fixed relationship relative to the diaphragm such that the second plurality of electrodes mechanically displace relative to the backplate as the function of pressure incident upon the diaphragm which mechanically displaces the diaphragm relative to the backplate; the first capacitor has a first capacitance which is a function of a displacement of the diaphragm relative to the backplate; and the second capacitor has a second capacitance which is a function of a displacement of the diaphragm relative to the backplate; and electrically coupling the first electrode to a first terminal of a voltage supply providing the alternating-current voltage waveform and electrically coupling the second electrode to a second terminal of the voltage supply.\",\n \"12.\",\n \"(canceled) 13.The method of claim 11, wherein the first capacitor and the second capacitor are electrically coupled to one another in a bridge structure, the bridge structure comprising: a third capacitor in series with the first capacitor and coupled between the first capacitor and the second terminal of the voltage supply; and a fourth capacitor in series with the second capacitor and coupled between the second capacitor and the first terminal of the voltage supply.\",\n \"14.The method of claim 13, further comprising detecting a direct-current voltage offset present in the bridge structure.\",\n \"15.The method of claim 14, further comprising controlling at least one of a third capacitance of the third capacitor and a fourth capacitance of the fourth capacitor responsive to the direct-current voltage offset.\",\n \"16.The method of claim 11, wherein the alternating-current voltage waveform has a frequency greater than that of human hearing.\",\n \"17.The method of claim 11, further comprising setting a magnitude of the alternating-current voltage waveform based on a magnitude of pressure upon the diaphragm in order to maximize a dynamic range of the microelectromechanical systems transducer.\",\n \"18.The method of claim 17, further comprising increasing the magnitude of the alternating-current voltage waveform as the pressure upon the diaphragm decreases and vice versa.\",\n \"19.The method of claim 11, further comprising measuring at least one of the first capacitance and the second capacitance.\",\n \"20.The method of claim 19, further comprising controlling a gain of the microelectromechanical systems transducer responsive to the measurement of at least one of the first capacitance and the second capacitance.\"\n ],\n [\n \" BACKGROUND Microphones are ubiquitous on many devices used by individuals, including computers, tablets, smart phones, and many other consumer devices.\",\n \"Generally speaking, a microphone is an electroacoustic transducer that produces an electrical signal in response to deflection of a portion (e.g., a membrane or other structure) of a microphone caused by sound incident upon the microphone.\",\n \"For example, a microphone may be implemented as a MEMS transducer.\",\n \"A MEMS transducer may include a diaphragm or membrane having an electrical capacitance to a reference plane or backplate, such that a change in acoustic pressure applied to the MEMS transducer causes a deflection or other movement of the membrane, and thus causes a change in the electrical capacitance.\",\n \"Such electrical capacitance or the change thereof may be sensed by a sensing circuit and processed.\",\n \"Existing MEMS microphone implementations are susceptible to a variety of electronic noise sources that may negatively affect a signal-to-noise ratio of a MEMS microphone.\",\n \"Among such noise sources are flicker noise (also known as 1/f noise) and noise bias resistors used in the biasing topology of existing approaches.\",\n \"Also, as with any audio system, it may be desirable to improve dynamic range of MEMS microphone implementations compared to that of existing implementations.\"\n ],\n [\n \" SUMMARY In accordance with the teachings of the present disclosure, certain disadvantages and problems associated with existing MEMS transducers may be reduced or eliminated.\",\n \"In accordance with embodiments of the present disclosure, a microelectromechanical systems microphone may include a backplate comprising a first plurality of electrodes comprising at least a first electrode and a second electrode electrically isolated from one another and each are mechanically coupled to the backplate in a fixed relationship relative to the backplate, and a diaphragm configured to mechanically displace relative to the backplate as a function of sound pressure incident upon the diaphragm, wherein the diaphragm comprises a second plurality of electrodes, the second plurality of electrodes comprising at least a third electrode and a fourth electrode, wherein the third electrode and the fourth electrode are electrically isolated from one another and each is mechanically coupled to the diaphragm in a fixed relationship relative to the diaphragm such that the second plurality of electrodes mechanically displace relative to the backplate as the function of sound pressure incident upon the diaphragm.\",\n \"The first electrode and the third electrode may form a first capacitor having a first capacitance which is a function of a displacement of the diaphragm relative to the backplate.\",\n \"The second electrode and the fourth electrode may form a second capacitor having a second capacitance which is a function of the displacement of the diaphragm relative to the backplate.\",\n \"Each of the first capacitor and the second capacitor may be biased by an alternating-current voltage waveform.\",\n \"In accordance with these and other embodiments of the present disclosure, a method may include biasing a first capacitor of an electromechanical systems microphone with an alternating-current voltage waveform and biasing a second capacitor of the electromechanical systems microphone with the alternating-current voltage waveform.\",\n \"The first capacitor may be formed from a first electrode and a third electrode and the second capacitor may be formed from a second electrode and a fourth electrode.\",\n \"The first electrode and the second electrode may be electrically isolated from one another and may each be mechanically coupled to a backplate in a fixed relationship relative to the backplate, the backplate comprising a first plurality of electrodes comprising the first electrode and the second electrode.\",\n \"The third electrode and the fourth electrode may be electrically isolated from one another and may each be mechanically coupled to a diaphragm in a fixed relationship relative to the diaphragm such that the second plurality of electrodes mechanically displace relative to the backplate as the function of sound pressure incident upon the diaphragm which mechanically displaces the diaphragm relative to the backplate.\",\n \"The first capacitor may have a first capacitance which is a function of a displacement of the diaphragm relative to the backplate and the second capacitor may have a second capacitance which is a function of a displacement of the diaphragm relative to the backplate.\",\n \"Technical advantages of the present disclosure may be readily apparent to one having ordinary skill in the art from the figures, description and claims included herein.\",\n \"The objects and advantages of the embodiments will be realized and achieved at least by the elements, features, and combinations particularly pointed out in the claims.\",\n \"It is to be understood that both the foregoing general description and the following detailed description are explanatory examples and are not restrictive of the claims set forth in this disclosure.\"\n ],\n [\n \"RELATED APPLICATIONS The present disclosure is related to U.S.\",\n \"Provisional Patent Application Ser.\",\n \"No.\",\n \"62/438,144, filed Dec. 22, 2016, which is incorporated by reference herein in its entirety.\",\n \"FIELD OF DISCLOSURE The present disclosure relates in general to audio systems, and more particularly, to improving the performance of microelectromechanical systems (MEMS) based transducers as compared to traditional approaches.\",\n \"BACKGROUND Microphones are ubiquitous on many devices used by individuals, including computers, tablets, smart phones, and many other consumer devices.\",\n \"Generally speaking, a microphone is an electroacoustic transducer that produces an electrical signal in response to deflection of a portion (e.g., a membrane or other structure) of a microphone caused by sound incident upon the microphone.\",\n \"For example, a microphone may be implemented as a MEMS transducer.\",\n \"A MEMS transducer may include a diaphragm or membrane having an electrical capacitance to a reference plane or backplate, such that a change in acoustic pressure applied to the MEMS transducer causes a deflection or other movement of the membrane, and thus causes a change in the electrical capacitance.\",\n \"Such electrical capacitance or the change thereof may be sensed by a sensing circuit and processed.\",\n \"Existing MEMS microphone implementations are susceptible to a variety of electronic noise sources that may negatively affect a signal-to-noise ratio of a MEMS microphone.\",\n \"Among such noise sources are flicker noise (also known as 1/f noise) and noise bias resistors used in the biasing topology of existing approaches.\",\n \"Also, as with any audio system, it may be desirable to improve dynamic range of MEMS microphone implementations compared to that of existing implementations.\",\n \"SUMMARY In accordance with the teachings of the present disclosure, certain disadvantages and problems associated with existing MEMS transducers may be reduced or eliminated.\",\n \"In accordance with embodiments of the present disclosure, a microelectromechanical systems microphone may include a backplate comprising a first plurality of electrodes comprising at least a first electrode and a second electrode electrically isolated from one another and each are mechanically coupled to the backplate in a fixed relationship relative to the backplate, and a diaphragm configured to mechanically displace relative to the backplate as a function of sound pressure incident upon the diaphragm, wherein the diaphragm comprises a second plurality of electrodes, the second plurality of electrodes comprising at least a third electrode and a fourth electrode, wherein the third electrode and the fourth electrode are electrically isolated from one another and each is mechanically coupled to the diaphragm in a fixed relationship relative to the diaphragm such that the second plurality of electrodes mechanically displace relative to the backplate as the function of sound pressure incident upon the diaphragm.\",\n \"The first electrode and the third electrode may form a first capacitor having a first capacitance which is a function of a displacement of the diaphragm relative to the backplate.\",\n \"The second electrode and the fourth electrode may form a second capacitor having a second capacitance which is a function of the displacement of the diaphragm relative to the backplate.\",\n \"Each of the first capacitor and the second capacitor may be biased by an alternating-current voltage waveform.\",\n \"In accordance with these and other embodiments of the present disclosure, a method may include biasing a first capacitor of an electromechanical systems microphone with an alternating-current voltage waveform and biasing a second capacitor of the electromechanical systems microphone with the alternating-current voltage waveform.\",\n \"The first capacitor may be formed from a first electrode and a third electrode and the second capacitor may be formed from a second electrode and a fourth electrode.\",\n \"The first electrode and the second electrode may be electrically isolated from one another and may each be mechanically coupled to a backplate in a fixed relationship relative to the backplate, the backplate comprising a first plurality of electrodes comprising the first electrode and the second electrode.\",\n \"The third electrode and the fourth electrode may be electrically isolated from one another and may each be mechanically coupled to a diaphragm in a fixed relationship relative to the diaphragm such that the second plurality of electrodes mechanically displace relative to the backplate as the function of sound pressure incident upon the diaphragm which mechanically displaces the diaphragm relative to the backplate.\",\n \"The first capacitor may have a first capacitance which is a function of a displacement of the diaphragm relative to the backplate and the second capacitor may have a second capacitance which is a function of a displacement of the diaphragm relative to the backplate.\",\n \"Technical advantages of the present disclosure may be readily apparent to one having ordinary skill in the art from the figures, description and claims included herein.\",\n \"The objects and advantages of the embodiments will be realized and achieved at least by the elements, features, and combinations particularly pointed out in the claims.\",\n \"It is to be understood that both the foregoing general description and the following detailed description are explanatory examples and are not restrictive of the claims set forth in this disclosure.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS A more complete understanding of the present embodiments and advantages thereof may be acquired by referring to the following description taken in conjunction with the accompanying drawings, in which like reference numbers indicate like features, and wherein: FIG.\",\n \"1 illustrates a block diagram of selected components of an example MEMS microphone, in accordance with embodiments of the present disclosure; and FIG.\",\n \"2 illustrates a block diagram of selected components of an example audio system comprising a MEMS microphone biased with an alternating-current voltage waveform, in accordance with embodiments of the present disclosure.\",\n \"DETAILED DESCRIPTION FIG.\",\n \"1 illustrates a block diagram of selected components of an example MEMS microphone 100, in accordance with embodiments of the present disclosure.\",\n \"As shown in FIG.\",\n \"1, MEMS microphone 100 may comprise a backplate 102, a diaphragm 108, and a substrate 114.Backplate 102 may include a plurality of electrodes comprising at least a first electrode 104 and a second electrode 106 electrically isolated from one another and each mechanically coupled to backplate 102 in a fixed relationship relative to backplate 102.For the purposes of clarity and exposition, only two electrodes 104 and 106 are depicted in FIG.\",\n \"1.In some embodiments, backplate 102 may include more than two electrodes.\",\n \"Diaphragm 108 may comprise a membrane or other structure configured to mechanically displace relative to the backplate as a function of sound pressure incident upon diaphragm (e.g., through acoustic port 118 of substrate 114).\",\n \"As shown in FIG.\",\n \"1, backplate 102 may be mechanically coupled to diaphragm 108 via a plurality of support posts 116 of backplate 102.Diaphragm 108 may include a plurality of electrodes comprising at least a third electrode 110 and a fourth electrode 112, in which third electrode 110 and fourth electrode 112 are electrically isolated from one another and each is mechanically coupled to diaphragm 108 in a fixed relationship relative to diaphragm 108 such that electrodes 110 and 112 mechanically displace relative to backplate 102 as the function of sound pressure incident upon diaphragm 108.Substrate 114 may comprise any suitable substrate or surface (e.g., a semiconductor substrate) upon which MEMS microphone 100 may be fabricated.\",\n \"The various components of MEMS microphone 100 (e.g., backplate 102, electrode 104, electrode 106, diaphragm 108, electrode 110, electrode 112, support posts 116, etc.)\",\n \"may be formed on substrate using semiconductor fabrication techniques now known or semiconductor fabrication techniques that may be known in the future.\",\n \"As also shown in FIG.\",\n \"1, substrate 114 may also have an acoustic port 118 formed therein (e.g., using semiconductor fabrication techniques now known or semiconductor fabrication techniques that may be known in the future) through which sound pressure may propagate to diaphragm 108 to displace diaphragm 108 as a function of such sound pressure.\",\n \"MEMS microphone 100 may be constructed such that first electrode 104 and third electrode 110 electrically interact with one another so as to form a first capacitor having a first capacitance which is a function of a displacement of diaphragm 108 relative to backplate 102.Similarly, MEMS microphone 100 may be constructed such that second electrode 106 and fourth electrode 112 electrically interact with one another so as to form a second capacitor having a second capacitance which is a function of a displacement of diaphragm 108 relative to backplate 102.The implementation shown in FIG.\",\n \"1 may be one of many ways to construct a MEMS microphone in accordance with the present disclosure.\",\n \"Accordingly, one or more other implementations may exist for a MEMS microphone which are substantially equivalent to that of MEMS microphone 100 depicted in FIG.\",\n \"1.FIG.\",\n \"2 illustrates a block diagram of selected components of an example audio system 200 comprising a MEMS microphone biased with an alternating-current voltage waveform, in accordance with embodiments of the present disclosure.\",\n \"As shown in FIG.\",\n \"2, audio system 200 may comprise a voltage supply 202, first capacitor 204 formed from first electrode 104 and third electrode 110, second capacitor 206 formed from second electrode 106 and fourth electrode 112, a third capacitor 208, a fourth capacitor 210, an amplifier 212, a demodulator 214, an analog-to-digital converter (ADC) 216, a direct-current voltage detector 218, a peak detector 220, a dynamic range enhancement controller 222, a capacitance measurement subsystem 224, a gain controller 226, and a gain element 228.Voltage supply 202 may comprise any suitable system, device, or apparatus configured to output an alternating-current (AC) bias voltage VBIAS for biasing first capacitor 204 and second capacitor 206, as described in greater detail below.\",\n \"In some embodiments, voltage supply 202 may generate AC bias voltage VBIAS as a square-wave voltage waveform.\",\n \"However, any suitable AC waveform may be used.\",\n \"Voltage supply 202 may be implemented in any suitable manner, including without limitation with a charge pump power supply.\",\n \"In some embodiments, AC bias voltage VBIAS may have a frequency greater than that of human hearing (e.g., greater than 20 kilohertz).\",\n \"As shown in FIG.\",\n \"2, first electrode 104 of first capacitor 204 may be electrically coupled to a first terminal of voltage supply 202 and second electrode 106 of second capacitor 206 may be electrically coupled to a second terminal of voltage supply 202.Accordingly, each of first capacitor 204 and second capacitor 206 may be biased by the alternating-current voltage waveform generated by voltage supply 202.Furthermore, as shown in FIG.\",\n \"2, first capacitor 204 and second capacitor 206 may be electrically coupled to one another in a bridge structure, the bridge structure comprising third capacitor 208 in series with first capacitor 204 and coupled between first capacitor 204 and the second terminal of voltage supply 202 and fourth capacitor 210 in series with second capacitor 206 and coupled between second capacitor 206 and the first terminal of voltage supply 202.In operation, a differential signal VCAP comprising the difference in potential between a third electrode 110 and fourth electrode 112 may be generated due to the presence of AC bias voltage VBIAS and sound pressure incident on diaphragm 108 which induces changes in capacitances of first capacitor 204 and second capacitor 206.Thus, differential signal VCAP may comprise an audio signal which is a function of the sound pressure incident on diaphragm 108, wherein such audio signal is modulated at a frequency of AC bias voltage VBIAS.\",\n \"Amplifier 212 may comprise any suitable system, device, or apparatus configured to amplify an analog signal received at its input (e.g., differential signal VCAP) to an amplified version of the input analog signal which may be more suitable for downstream processing.\",\n \"Demodulator 214 may comprise any suitable system, device, or apparatus configured to extract from an analog signal (e.g., differential signal VCAP as amplified by amplifier 212) an information-bearing signal (e.g., analog microphone signal VMIC) from a modulated carrier wave (e.g., a modulated carrier wave at the frequency of AC bias voltage VBIAS).\",\n \"In some embodiments, demodulator 214 may comprise a synchronous modulator.\",\n \"ADC 216 may comprise any suitable system, device, or apparatus configured to convert an analog signal (e.g., analog microphone signal VMIC) into a corresponding digital signal (e.g., digital microphone signal MIC_DIG).\",\n \"Direct-current voltage detector 218 may comprise any suitable system, device, or apparatus configured to receive digital microphone signal MIC_DIG and analyze such signal in order to detect a direct-current voltage offset present in differential signal VCAP of the bridge structure comprising capacitors 204, 206, 208, and 210.Based on the detected direct-current voltage offset present in differential signal VCAP, direct-current voltage detector 218 may generate a direct-current compensation control signal DC_COMP to control at least one of the third capacitance of third capacitor 208 and the fourth capacitance of fourth capacitor 210 responsive to the direct-current voltage offset in order to compensate for the presence of the direct-current voltage offset.\",\n \"Peak detector 220 may include any suitable system, device, or apparatus configured to receive analog microphone signal VMIC (or a derivative thereof), determine a magnitude of such signal, and output a peak amplitude signal PEAK indicative of such magnitude.\",\n \"Dynamic range enhancement controller 222 may include any suitable system, device, or apparatus configured to receive peak amplitude signal PEAK and based thereon, determine an analog gain for audio system 200 and generate an analog gain signal ANALOG_GAIN indicative of such analog gain.\",\n \"Analog gain signal ANALOG_GAIN may be used as a control signal in order to set a magnitude of AC bias voltage VBIAS.\",\n \"Accordingly, the magnitude of AC bias voltage VBIAS may be set based on the magnitude of sound pressure upon diaphragm 108 in order to maximize a dynamic range of microelectromechanical systems microphone 100 and audio system 200.For example, to maximize dynamic range, dynamic range enhancement controller 222 may cause the magnitude of AC bias voltage VBIAS to increase as the sound pressure upon diaphragm 108 decreases, and cause the magnitude of AC bias voltage VBIAS to decrease as the sound pressure upon diaphragm 108 increases.\",\n \"Capacitance measurement subsystem 224 may include any suitable system, device, or apparatus configured to measure a capacitance of first capacitor 204 (as explicitly shown in FIG.\",\n \"2) and/or second capacitor 206 and output a gain compensation signal GAIN_COMP indicative of such measured capacitance.\",\n \"Such capacitance may be indicative of the sensitivity of measurement of audio system 200, and thus, as described below, may be used to compensate for such sensitivity.\",\n \"Gain controller 226 may include any suitable system, device, or apparatus configured to receive analog gain signal ANALOG_GAIN and/or gain compensation signal GAIN_COMP and based thereon, generate a digital gain signal DIG_GAIN, which may be used by gain element 228 to control a digital gain applied to digital microphone signal MIC_DIG to generate an audio output signal AUDIO_OUT of audio system 200.Accordingly, digital gain signal DIG_GAIN may include two components.\",\n \"First, the level of digital gain indicated by digital gain signal DIG_GAIN may be based on an inverse of analog gain indicated by analog gain signal ANALOG_GAIN, in order to offset the analog gain applied in audio system 200 (e.g., to voltage supply 202) to maximize dynamic range.\",\n \"Second, the level of digital gain indicated by digital gain signal DIG_GAIN may also control a gain of audio system 200 responsive to the sensitivity of measurement, as may be indicated by the first capacitance of capacitor 204 and/or the second capacitance of capacitor 206.Advantageously, the systems and methods herein may provide an improvement over existing MEMS microphone implementations.\",\n \"For example, replacing the direct-current (DC) biasing present in existing approaches with the AC biasing approach of the systems and methods disclosed herein creates a signal of interest modulated by a frequency of AC bias voltage VBIAS, reducing or eliminating flicker noise and/or bias resistor noise that is typically present at low frequencies or at DC.\",\n \"In addition, because of the symmetric excitation applied to the capacitor bridge of audio system 200, the magnitude of AC bias voltage VBIAS may be modified without disturbing a bias point of the sensing amplifier (e.g., amplifier 212) of audio system 200.Accordingly, such magnitude of AC bias voltage VBIAS may be modified as a function of the magnitude of the acoustic pressure incident upon MEMS microphone 100, thus maximizing the dynamic range of MEMS microphone 100 and audio system 200.Furthermore, unlike DC-biased implementations, in which only the change in capacitance of MEMS microphone 100 can be measured but not the static capacitance, in the systems and methods described herein, such static capacitance can be measured, allowing for collection of additional information regarding audio system 200 (e.g., sensitivity), for which audio system 200 may make further adjustments to improve accuracy.\",\n \"This disclosure encompasses all changes, substitutions, variations, alterations, and modifications to the example embodiments herein that a person having ordinary skill in the art would comprehend.\",\n \"Similarly, where appropriate, the appended claims encompass all changes, substitutions, variations, alterations, and modifications to the example embodiments herein that a person having ordinary skill in the art would comprehend.\",\n \"Moreover, reference in the appended claims to an apparatus or system or a component of an apparatus or system being adapted to, arranged to, capable of, configured to, enabled to, operable to, or operative to perform a particular function encompasses that apparatus, system, or component, whether or not it or that particular function is activated, turned on, or unlocked, as long as that apparatus, system, or component is so adapted, arranged, capable, configured, enabled, operable, or operative.\",\n \"All examples and conditional language recited herein are intended for pedagogical objects to aid the reader in understanding the disclosure and the concepts contributed by the inventor to furthering the art, and are construed as being without limitation to such specifically recited examples and conditions.\",\n \"Although embodiments of the present disclosure have been described in detail, it should be understood that various changes, substitutions, and alterations could be made hereto without departing from the spirit and scope of the disclosure.\"\n ]\n]"},"source":{"kind":"string","value":"Patent_15872019"}}},{"rowIdx":4493984,"cells":{"text":{"kind":"list like","value":[["Wheel Bearing Apparatus","The wheel bearing apparatus has hub bolts (6a) to fasten a wheel secured equidistantly around the wheel mounting flange (6).","An annular groove (7a) is formed on the outer-side surface (7) of the wheel mounting flange (6).","The annular groove (7a) includes a region where the hub bolts (6a) are mounted.","The outer-side surface (7) of the wheel mounting flange (6) is formed as a cut surface cut after press-fitting of the hub bolts (6a).","Weight reduction apertures (circular apertures) (13) are formed between the hub bolts 6a of the wheel mounting flange (6).","A diameter of a circumscribed circle øA circumscribing the circular apertures (13) is set larger than an outer diameter øB of the annular groove (7a).","Accordingly, muddy water is easily discharged from the circular apertures (13)."],["1.A wheel bearing apparatus comprising: an outer member, an outer member inner circumference includes double row outer raceway surfaces; an inner member, an inner member outer circumferences includes double row inner raceway surfaces opposing the double row outer raceway surfaces; double row rolling elements are rollably accommodated in a space between the inner raceway surfaces of the inner member and the outer raceway surfaces of the outer member; a wheel mounting flange for mounting a wheel, via a brake disc, is formed on a rotary-side of one of the outer member or the inner member; hub bolts, to fasten the wheel, are secured equidistantly along the wheel mounting flange; an annular groove is formed on the outer-side surface of the wheel mounting flange, the annular groove includes a region where the hub bolts are mounted, weight reduction apertures are formed between hub bolts on the wheel mounting flange, a diameter of a circumscribed circle circumscribing the weight reduction apertures is set larger than an outer diameter of the annular groove or the weight reduction apertures are opened to an outer circumferential surface of the wheel mounting flange.","2.The wheel bearing apparatus of claim 1, wherein the outer-side surface of the wheel mounting flange is formed as a cut surface cut after press-fitting of the hub bolts.","3.The wheel bearing apparatus of claim 1, wherein each of the weight reduction apertures of the wheel mounting flange is formed as a tapered aperture gradually expanding toward the inner-side.","4.The wheel bearing apparatus of claim 1, wherein radially extending drain grooves are formed by cutting a portion adjacent each weight reduction aperture of the wheel mounting flange.","5.The wheel bearing apparatus of claim 1, wherein a radially extending reinforcing rib is formed as a build-up part on the inner-side surface of the wheel mounting flange in a region in which the hub bolt is secured.","6.The wheel bearing apparatus of claim 1, wherein cut-off parts are formed on the outer circumference of the wheel mounting flange between bolt apertures where the hub bolts are press-fit, the cut-off parts keeping clear of near the bolt apertures, and each of the cut-off parts is formed with a circular arc shape so that deepest portions of the cut-off parts are positioned in proximity to a pitch circle diameter of the bolt apertures.","7.The wheel bearing apparatus of claim 6, wherein a diameter of the deepest portions of the cut-off parts is smaller than an outer diameter of the annular groove."],[" BACKGROUND In general, disc brakes are superior in braking performance and have become very popular.","However, a problem exists in that the disc brakes cause vibrations and thus uncomfortable noise at low frequency especially at low speed traveling when braking, sandwiching a brake rotor between brake pads.","Such a phenomenon is called brake judder.","It has been recently noticed as a new subject in technology requiring analysis and improvement due to a desire to achieve high performance as well as silence in the vehicle.","Although theoretical mechanisms causing brake judder have not been found yet, it is believed that one factor is the accuracy of plane deflection of a pad sliding surface.","The accuracy of plane deflection appears as a plane deflection of a side surface of the brake rotor due to accumulation of not only the plane deflection accuracies of the brake rotor itself but the wheel mounting flange on which the brake rotor is mounted, axial deflection of the rolling bearings, accuracy of the inner or outer raceway surfaces and the assembling accuracy of the rolling bearings.","In recent years, measures, for the plane deflection accuracy of the side surface of brake rotor described above, have been taken with satisfying conflicting demands of reduction of size and weight of the wheel bearing apparatus.","This improves fuel consumption and increases the rigidity of the wheel bearing apparatus to improve driving stability of the vehicle.","One example of a known wheel bearing apparatus is shown in FIG.","7 .","This wheel bearing apparatus has an inner member 50 , an outer member 60 and double row rolling elements 70 , 70 .","The inner member 50 has a wheel hub 51 and an inner ring 52 press-fit onto a cylindrical portion 53 of the wheel hub 51 .","One inner raceway surface 51 a is formed on the outer circumference of the wheel hub 51 .","The other inner raceway surface 52 a is formed on the outer circumference of the inner ring 52 .","The wheel hub 51 is integrally formed, on its outer-side end, with a wheel mounting flange 54 to mount a wheel (not shown).","Hub bolts 55 are mounted equidistantly on the wheel mounting flange 54 .","On the other hand, the outer member 60 is formed, on its outer circumference, with a body mounting flange 61 adapted to be mounted on a body (not shown) of a vehicle.","The outer member inner circumference includes double row outer raceway surfaces 60 a , 60 a .","The double row rolling elements (balls) 70 , 70 are rollably accommodated between the inner and outer raceway surfaces 51 a , 52 a and 60 a , 60 a , via cages 71 , 71 .","Seals 62 , 63 are mounted on both end of the outer member 60 to seal annular spaces between the outer member 60 and the inner member 50 .","This prevents leakage of lubricating grease confined within the bearing and entry of rain water or dust from the outside into the bearing.","An annular groove 56 is formed on the outer-side surface 54 a of the wheel mounting flange 54 .","Bolt apertures 57 are formed equidistantly along and in the annular groove 56 .","The hub bolts 55 are secured in the bolt apertures 57 by press-fitting knurled portions 55 a of the hub bolts 55 into the bolt apertures 57 .","A wheel is adapted to be secured on the wheel mounting flange 54 , via the brake rotor (not shown), by fastening nuts (not shown) onto the hub bolts 55 .","The outer-side surface 54 a of the wheel mounting flange 54 is finished processed by grinding after press-fitting of the hub bolts 55 .","This enables the deformation around the bolt aperture 57 or undulations of the side surface 54 a generated by forming the bolt apertures 57 in the annular groove 56 and press-fitting the hub bolts 55 to mainly occur within the annular groove 56 as well as to suppress the influences to the accuracy of plane deflection of the side surface 54 a caused by press-fitting of the hub bolts 55 to substantially zero.","See, JP2003-154801 A.","However, in the prior art wheel bearing apparatus, when circular apertures (weight reduction apertures) 80 are formed between the hub bolts 55 , as shown in FIG.","8( a ) , muddy water etc.","that enters through the weight reduction apertures 80 and often remains in a clearance between the outer-side surface 54 a of the wheel mounting flange 54 and a side surface 81 a of the brake rotor 81 .","Thus, rusts is generated on the contact surfaces between the two.","As a result, the accuracy of the plane deflection of the side surface 54 a of the wheel mounting flange 54 becomes worse.","Thus, it is believed that brake judder would be caused as well as the brake rotor 81 strongly fixed to the wheel mounting flange 54 , via rust.","Thus, disassembly of the brake rotor 81 from the wheel mounting flange 54 would be difficult.","The present disclosure has been achieved with focus on a structure that easily discharges muddy water etc.","entering through the weight reduction apertures of the wheel mounting flange while preventing the muddy water etc.","from remaining in a clearance space between the wheel mounting flange and the brake rotor.","Thus, it is an object of the present disclosure to provide a wheel bearing apparatus that reduces its weight and improves reliability while enhancing the accuracy of the plane deflection of the wheel mounting flange and thus suppressing the generation of brake judder."],[" SUMMARY To achieve the above objects, a wheel bearing apparatus comprises an outer member, an inner member and double row rolling elements.","The outer member includes double row outer raceway surfaces on its inner circumference.","The inner member outer circumference includes double row inner raceway surfaces.","The inner raceway surfaces oppose the double row outer raceway surfaces.","The double row rolling elements are rollably accommodated in a space between the inner raceway surfaces of the inner member and the outer raceway surfaces of the outer member.","A wheel mounting flange, for mounting a wheel via a brake disc, is mounted on a rotary-side of one of the outer member or the inner member.","Hub bolts, for fastening the wheel, are secured equidistantly along the wheel mounting flange.","An annular groove is formed on the outer-side surface of the wheel mounting flange.","The annular groove includes a region where the hub bolts are mounted.","Weight reduction apertures are formed between the hub bolts of the wheel mounting flange.","A diameter of a circumscribed circle circumscribing the weight reduction apertures is set larger than an outer diameter of the annular groove or the weight reduction apertures are opened to an outer circumferential surface of the wheel mounting flange.","The wheel bearing apparatus has a wheel mounting flange, to mount a wheel via a brake disc, mounted on a rotary-side of one of the outer member or the inner member.","Hub bolts, to fasten the wheel, are secured equidistantly along the wheel mounting flange.","An annular groove is formed on the outer-side surface of the wheel mounting flange.","The annular groove includes a region where the hub bolts are mounted.","Weight reduction apertures are formed between hub bolts on the wheel mounting flange.","A diameter of a circumscribed circle circumscribing the weight reduction apertures is set larger than an outer diameter of the annular groove or the weight reduction apertures are opened to an outer circumferential surface of the wheel mounting flange.","Thus, it is possible to provide a wheel bearing apparatus that easily discharges muddy water etc.","entering into the weight reduction apertures of the wheel mounting flange while preventing the muddy water etc.","from remaining in a clearance gap between the outer-side surface of the wheel mounting flange and the side surface of the brake disc.","The wheel bearing apparatus can reduce its own weight and improve reliability while enhancing the accuracy of the plane deflection of the wheel mounting flange and thus suppress the generation of brake judder.","The outer-side surface of the wheel mounting flange is formed as a cut surface.","It is cut after press-fitting of the hub bolts.","This makes it possible to achieve the finish process by a simple turning process and thus reduce the manufacturing cost.","In addition, it is possible to suppress the generation of brake judder while enhancing the accuracy of the plane deflection of the wheel mounting flange by reducing influences on the plane deflection due to press-fitting of hub bolts.","Each of the weight reduction apertures in the wheel mounting flange is formed as a tapered aperture gradually expanding toward the inner-side.","This makes it possible to easily discharge muddy water etc.","from the weight reduction apertures while preventing the muddy water etc.","from remaining in a clearance space between the wheel mounting flange and the brake disc.","Radially extending drain grooves are formed by cutting a portion of each weight reduction aperture of the wheel mounting flange.","This makes it possible to easily discharge muddy water etc.","from the weight reduction apertures through the drain grooves even though the weight reduction apertures are formed within a region of the annular groove.","This prevents the muddy water etc.","from remaining in a clearance gap between the wheel mounting flange and the brake disc.","A radially extending reinforcing rib is formed, as a build-up part, on the inner-side surface of the wheel mounting flange.","It is formed in a region where the hub bolt is secured.","This makes it possible to reduce the weight of the wheel mounting flange while keeping its strength and rigidity.","Cut-off parts are formed on the outer circumference of the wheel mounting flange between the bolt apertures.","The hub bolts are press-fit into the aperture while keeping clear or near the bolt apertures.","Each of the cut-off parts are formed with a circular arc shape so that the deepest portions of the cut-off parts are positioned in proximity to a pitch circle diameter of the bolt apertures.","This makes it possible to reduce the weight and size of the wheel mounting flange while keeping its strength and rigidity.","Also, it suppresses the generation of brake judder while enhancing the accuracy of the plane deflection of the wheel mounting flange by reducing deformation of the wheel mounting flange due to its heat treatment.","A diameter of the deepest portions of the cut-off parts is smaller than an outer diameter of the annular groove.","This makes it possible to make the weight reduction apertures open to the outer circumference of the wheel mounting flange.","Accordingly, it is possible to easily discharge muddy water etc.","entering into the weight reduction apertures of the wheel mounting flange through the deepest portions of the cut-off parts.","This prevents the muddy water etc.","from remaining in a clearance space between the wheel mounting flange and the brake disc.","This also reduces the wheel bearing assembly's own weight and improves reliability while enhancing the accuracy of the plane deflection of the wheel mounting flange and thus suppresses the generation of brake judder.","The wheel bearing apparatus has an outer member, inner member and double row rolling elements.","The outer member inner circumference includes double row outer raceway surfaces.","The inner member outer circumferences include double row inner raceway surfaces opposing the double row outer raceway surfaces.","The double row rolling elements are rollably accommodated in a space between the inner raceway surfaces of the inner member and the outer raceway surfaces of the outer member.","A wheel mounting flange, to mount a wheel via a brake disc, is mounted on a rotary-side of one of the outer member or the inner member.","Hub bolts, to fasten the wheel, are secured equidistantly along the wheel mounting flange.","An annular groove is formed on the outer-side surface of the wheel mounting flange.","The annular groove has a region where the hub bolts are mounted.","Weight reduction apertures are formed between hub bolts of the wheel mounting flange.","A diameter of a circumscribed circle circumscribing the weight reduction apertures is set larger than an outer diameter of the annular groove or the weight reduction apertures are opened to an outer circumferential surface of the wheel mounting flange.","Thus, it is possible to provide a wheel bearing apparatus that can easily discharge muddy water etc.","entering into the weight reduction apertures of the wheel mounting flange while preventing the muddy water etc.","from remaining in a clearance space between the wheel mounting flange and the brake disc.","This also reduces the wheel bearing assembly's own weight and improves reliability while enhancing the accuracy of the plane deflection of the wheel mounting flange and thus suppress the generation of brake judder.","Further areas of applicability will become apparent from the description provided herein.","The description and specific examples in this summary are intended for purposes of illustration only and are not intended to limit the scope of the present disclosure."],["CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of International Application No.","PCT/JP2016/070914, filed Jul.","14, 2016, which claims priority to Japanese Application No.","2015-141921, filed Jul.","16, 2015.The disclosures of the above applications are incorporating herein by reference.","FIELD The present disclosure relates to a wheel bearing apparatus that rotationally bears the weight of a vehicle wheel, such as an automobile, and, more particularly, to a wheel bearing apparatus that reduces the weight of the wheel bearing apparatus as well as suppress the generation of brake judder while enhancing the accuracy of the plane deflection of a wheel mounting flange.","Thus, this improves the reliability of the wheel bearing apparatus.","BACKGROUND In general, disc brakes are superior in braking performance and have become very popular.","However, a problem exists in that the disc brakes cause vibrations and thus uncomfortable noise at low frequency especially at low speed traveling when braking, sandwiching a brake rotor between brake pads.","Such a phenomenon is called brake judder.","It has been recently noticed as a new subject in technology requiring analysis and improvement due to a desire to achieve high performance as well as silence in the vehicle.","Although theoretical mechanisms causing brake judder have not been found yet, it is believed that one factor is the accuracy of plane deflection of a pad sliding surface.","The accuracy of plane deflection appears as a plane deflection of a side surface of the brake rotor due to accumulation of not only the plane deflection accuracies of the brake rotor itself but the wheel mounting flange on which the brake rotor is mounted, axial deflection of the rolling bearings, accuracy of the inner or outer raceway surfaces and the assembling accuracy of the rolling bearings.","In recent years, measures, for the plane deflection accuracy of the side surface of brake rotor described above, have been taken with satisfying conflicting demands of reduction of size and weight of the wheel bearing apparatus.","This improves fuel consumption and increases the rigidity of the wheel bearing apparatus to improve driving stability of the vehicle.","One example of a known wheel bearing apparatus is shown in FIG.","7.This wheel bearing apparatus has an inner member 50, an outer member 60 and double row rolling elements 70, 70.The inner member 50 has a wheel hub 51 and an inner ring 52 press-fit onto a cylindrical portion 53 of the wheel hub 51.One inner raceway surface 51a is formed on the outer circumference of the wheel hub 51.The other inner raceway surface 52a is formed on the outer circumference of the inner ring 52.The wheel hub 51 is integrally formed, on its outer-side end, with a wheel mounting flange 54 to mount a wheel (not shown).","Hub bolts 55 are mounted equidistantly on the wheel mounting flange 54.On the other hand, the outer member 60 is formed, on its outer circumference, with a body mounting flange 61 adapted to be mounted on a body (not shown) of a vehicle.","The outer member inner circumference includes double row outer raceway surfaces 60a, 60a.","The double row rolling elements (balls) 70, 70 are rollably accommodated between the inner and outer raceway surfaces 51a, 52a and 60a, 60a, via cages 71, 71.Seals 62, 63 are mounted on both end of the outer member 60 to seal annular spaces between the outer member 60 and the inner member 50.This prevents leakage of lubricating grease confined within the bearing and entry of rain water or dust from the outside into the bearing.","An annular groove 56 is formed on the outer-side surface 54a of the wheel mounting flange 54.Bolt apertures 57 are formed equidistantly along and in the annular groove 56.The hub bolts 55 are secured in the bolt apertures 57 by press-fitting knurled portions 55a of the hub bolts 55 into the bolt apertures 57.A wheel is adapted to be secured on the wheel mounting flange 54, via the brake rotor (not shown), by fastening nuts (not shown) onto the hub bolts 55.The outer-side surface 54a of the wheel mounting flange 54 is finished processed by grinding after press-fitting of the hub bolts 55.This enables the deformation around the bolt aperture 57 or undulations of the side surface 54a generated by forming the bolt apertures 57 in the annular groove 56 and press-fitting the hub bolts 55 to mainly occur within the annular groove 56 as well as to suppress the influences to the accuracy of plane deflection of the side surface 54a caused by press-fitting of the hub bolts 55 to substantially zero.","See, JP2003-154801 A.","However, in the prior art wheel bearing apparatus, when circular apertures (weight reduction apertures) 80 are formed between the hub bolts 55, as shown in FIG.","8(a), muddy water etc.","that enters through the weight reduction apertures 80 and often remains in a clearance between the outer-side surface 54a of the wheel mounting flange 54 and a side surface 81a of the brake rotor 81.Thus, rusts is generated on the contact surfaces between the two.","As a result, the accuracy of the plane deflection of the side surface 54a of the wheel mounting flange 54 becomes worse.","Thus, it is believed that brake judder would be caused as well as the brake rotor 81 strongly fixed to the wheel mounting flange 54, via rust.","Thus, disassembly of the brake rotor 81 from the wheel mounting flange 54 would be difficult.","The present disclosure has been achieved with focus on a structure that easily discharges muddy water etc.","entering through the weight reduction apertures of the wheel mounting flange while preventing the muddy water etc.","from remaining in a clearance space between the wheel mounting flange and the brake rotor.","Thus, it is an object of the present disclosure to provide a wheel bearing apparatus that reduces its weight and improves reliability while enhancing the accuracy of the plane deflection of the wheel mounting flange and thus suppressing the generation of brake judder.","SUMMARY To achieve the above objects, a wheel bearing apparatus comprises an outer member, an inner member and double row rolling elements.","The outer member includes double row outer raceway surfaces on its inner circumference.","The inner member outer circumference includes double row inner raceway surfaces.","The inner raceway surfaces oppose the double row outer raceway surfaces.","The double row rolling elements are rollably accommodated in a space between the inner raceway surfaces of the inner member and the outer raceway surfaces of the outer member.","A wheel mounting flange, for mounting a wheel via a brake disc, is mounted on a rotary-side of one of the outer member or the inner member.","Hub bolts, for fastening the wheel, are secured equidistantly along the wheel mounting flange.","An annular groove is formed on the outer-side surface of the wheel mounting flange.","The annular groove includes a region where the hub bolts are mounted.","Weight reduction apertures are formed between the hub bolts of the wheel mounting flange.","A diameter of a circumscribed circle circumscribing the weight reduction apertures is set larger than an outer diameter of the annular groove or the weight reduction apertures are opened to an outer circumferential surface of the wheel mounting flange.","The wheel bearing apparatus has a wheel mounting flange, to mount a wheel via a brake disc, mounted on a rotary-side of one of the outer member or the inner member.","Hub bolts, to fasten the wheel, are secured equidistantly along the wheel mounting flange.","An annular groove is formed on the outer-side surface of the wheel mounting flange.","The annular groove includes a region where the hub bolts are mounted.","Weight reduction apertures are formed between hub bolts on the wheel mounting flange.","A diameter of a circumscribed circle circumscribing the weight reduction apertures is set larger than an outer diameter of the annular groove or the weight reduction apertures are opened to an outer circumferential surface of the wheel mounting flange.","Thus, it is possible to provide a wheel bearing apparatus that easily discharges muddy water etc.","entering into the weight reduction apertures of the wheel mounting flange while preventing the muddy water etc.","from remaining in a clearance gap between the outer-side surface of the wheel mounting flange and the side surface of the brake disc.","The wheel bearing apparatus can reduce its own weight and improve reliability while enhancing the accuracy of the plane deflection of the wheel mounting flange and thus suppress the generation of brake judder.","The outer-side surface of the wheel mounting flange is formed as a cut surface.","It is cut after press-fitting of the hub bolts.","This makes it possible to achieve the finish process by a simple turning process and thus reduce the manufacturing cost.","In addition, it is possible to suppress the generation of brake judder while enhancing the accuracy of the plane deflection of the wheel mounting flange by reducing influences on the plane deflection due to press-fitting of hub bolts.","Each of the weight reduction apertures in the wheel mounting flange is formed as a tapered aperture gradually expanding toward the inner-side.","This makes it possible to easily discharge muddy water etc.","from the weight reduction apertures while preventing the muddy water etc.","from remaining in a clearance space between the wheel mounting flange and the brake disc.","Radially extending drain grooves are formed by cutting a portion of each weight reduction aperture of the wheel mounting flange.","This makes it possible to easily discharge muddy water etc.","from the weight reduction apertures through the drain grooves even though the weight reduction apertures are formed within a region of the annular groove.","This prevents the muddy water etc.","from remaining in a clearance gap between the wheel mounting flange and the brake disc.","A radially extending reinforcing rib is formed, as a build-up part, on the inner-side surface of the wheel mounting flange.","It is formed in a region where the hub bolt is secured.","This makes it possible to reduce the weight of the wheel mounting flange while keeping its strength and rigidity.","Cut-off parts are formed on the outer circumference of the wheel mounting flange between the bolt apertures.","The hub bolts are press-fit into the aperture while keeping clear or near the bolt apertures.","Each of the cut-off parts are formed with a circular arc shape so that the deepest portions of the cut-off parts are positioned in proximity to a pitch circle diameter of the bolt apertures.","This makes it possible to reduce the weight and size of the wheel mounting flange while keeping its strength and rigidity.","Also, it suppresses the generation of brake judder while enhancing the accuracy of the plane deflection of the wheel mounting flange by reducing deformation of the wheel mounting flange due to its heat treatment.","A diameter of the deepest portions of the cut-off parts is smaller than an outer diameter of the annular groove.","This makes it possible to make the weight reduction apertures open to the outer circumference of the wheel mounting flange.","Accordingly, it is possible to easily discharge muddy water etc.","entering into the weight reduction apertures of the wheel mounting flange through the deepest portions of the cut-off parts.","This prevents the muddy water etc.","from remaining in a clearance space between the wheel mounting flange and the brake disc.","This also reduces the wheel bearing assembly's own weight and improves reliability while enhancing the accuracy of the plane deflection of the wheel mounting flange and thus suppresses the generation of brake judder.","The wheel bearing apparatus has an outer member, inner member and double row rolling elements.","The outer member inner circumference includes double row outer raceway surfaces.","The inner member outer circumferences include double row inner raceway surfaces opposing the double row outer raceway surfaces.","The double row rolling elements are rollably accommodated in a space between the inner raceway surfaces of the inner member and the outer raceway surfaces of the outer member.","A wheel mounting flange, to mount a wheel via a brake disc, is mounted on a rotary-side of one of the outer member or the inner member.","Hub bolts, to fasten the wheel, are secured equidistantly along the wheel mounting flange.","An annular groove is formed on the outer-side surface of the wheel mounting flange.","The annular groove has a region where the hub bolts are mounted.","Weight reduction apertures are formed between hub bolts of the wheel mounting flange.","A diameter of a circumscribed circle circumscribing the weight reduction apertures is set larger than an outer diameter of the annular groove or the weight reduction apertures are opened to an outer circumferential surface of the wheel mounting flange.","Thus, it is possible to provide a wheel bearing apparatus that can easily discharge muddy water etc.","entering into the weight reduction apertures of the wheel mounting flange while preventing the muddy water etc.","from remaining in a clearance space between the wheel mounting flange and the brake disc.","This also reduces the wheel bearing assembly's own weight and improves reliability while enhancing the accuracy of the plane deflection of the wheel mounting flange and thus suppress the generation of brake judder.","Further areas of applicability will become apparent from the description provided herein.","The description and specific examples in this summary are intended for purposes of illustration only and are not intended to limit the scope of the present disclosure.","DRAWINGS The drawings described herein are for illustrative purposes only of selected embodiments and not all possible implementations, and are not intended to limit the scope of the present disclosure.","FIG.","1 is a longitudinal section view of a first embodiment of the wheel bearing apparatus of the present disclosure.","FIG.","2 is a side elevation view of a wheel hub of FIG.","1.FIG.","3 is a partially enlarged view of a weight reduction aperture of FIG.","1.FIG.","4(a) is a side elevation view of one modification of FIG.","1.FIG.","4(b) is a partially enlarged view of a weight reduction aperture of FIG.","4(a).","FIG.","5(a) is a side elevation view of another modification of FIG.","1.FIG.","5(b) is a partially enlarged view of a weight reduction aperture of FIG.","5(a).","FIG.","6(a) is a side elevation view of a second embodiment of the wheel bearing apparatus.","FIG.","6(b) is a longitudinal section view of FIG.","6(a).","FIG.","6(c) is a partially enlarged view of a weight reduction aperture of FIG.","6(b).","FIG.","7(a) is a side elevation view of a prior art wheel bearing apparatus.","FIG.","7(b) is a longitudinal section view of FIG.","7(a).","FIG.","8(a) is a side elevation view of a wheel bearing apparatus where weight reduction apertures are formed in a wheel mounting flange of FIG.","7(a).","FIG.","8(b) is a partially enlarged view of a weight reduction aperture of FIG.","8(a).","DETAILED DESCRIPTION The present disclosure is a wheel bearing apparatus with an outer member, inner member and rolling members.","The outer member outer circumference includes a body mounting flange to be mounted on a knuckle forming a suspension apparatus.","The outer member inner circumference includes double row outer raceway surfaces.","The inner member includes a wheel hub and an inner ring.","The wheel hub is integrally formed, on its one end, with a wheel mounting flange.","The wheel hub outer circumference includes an inner raceway surface opposing one of the double row outer raceway surfaces.","A cylindrical portion axially extends from the inner raceway surface.","The inner ring is press-fit onto the cylindrical portion of the wheel hub.","The inner ring outer circumference includes an inner raceway surface opposing the other of the double row outer raceway surfaces.","The double row rolling elements are rollably accommodated in a space between the inner raceway surfaces of the inner member and the outer raceway surfaces of the outer member.","Hub bolts, to fasten a wheel mounted on the wheel mounting flange, are equidistantly position along the wheel mounting flange.","An annular groove is formed on the outer-side surface of the wheel mounting flange.","The annular groove includes a region where the hub bolts are mounted.","The outer-side surface of the wheel mounting flange is formed as a cut surface, cut after press-fitting of the hub bolts.","Weight reduction apertures are formed between hub bolts on the wheel mounting flange.","A diameter of a circumscribed circle circumscribing the weight reduction apertures is set larger than an outer diameter of the annular groove.","Embodiments will be described with reference to the accompanied drawings.","FIG.","1 is a longitudinal section view of a first embodiment of the wheel bearing apparatus.","FIG.","2 is a side elevation view of a wheel hub of FIG.","1.FIG.","3 is a partially enlarged view of a weight reduction aperture of FIG.","1.FIG.","4(a) is a side elevation view of one modification of FIG.","1.FIG.","4(b) is a partially enlarged view of a weight reduction aperture of FIG.","4(a).","FIG.","5(a) is a side elevation view of another modification of FIG.","1.FIG.","5(b) is a partially enlarged view of a weight reduction aperture of FIG.","5(a).","In the description of this specification, an outer-side of a bearing apparatus, when it is mounted on a vehicle, is referred to as the “outer-side” (left-side in FIG.","1(b)).","An inner-side of a bearing apparatus, when it is mounted on a vehicle, is referred to as the “inner-side” (right-side in FIG.","1(b)).","The wheel bearing apparatus shown in FIG.","1 is a so-called “third generation” type for a driving wheel.","It includes an inner member 3 including a wheel hub 1 and an inner ring 2 press-fit onto the wheel hub 1.An outer member 5 is mounted on the inner member 3, via a double row rolling elements (balls) 4, 4.The wheel hub 1 is integrally formed, on its outer-side end, with a wheel mounting flange 6.The flange 6 mounts a wheel, via a brake disc or a brake drum (not shown).","The wheel hub outer circumference includes one (outer-side) inner raceway surface 1a.","A cylindrical portion 1b axially extends from the inner raceway surface 1a.","A serration (or spline) 1c, for torque transmission, is formed on the inner circumference of the wheel hub 1.Hub bolts 6a are secured at circumferentially equidistant positions on the wheel mounting flange 6.The inner ring 2 is formed, on its outer circumference, with an inner raceway surface 2a.","The inner ring 2 is press-fit, via a predetermined interference, onto the outer circumference of the cylindrical portion 1b of the wheel hub 1.The inner ring 2 is axially secured on the cylindrical portion 1b by a caulked portion 1d.","The caulked portion 1d is formed by plastically deforming radially outward an end of the cylindrical portion 1b under a predetermined bearing pre-pressure.","An outer-side surface 7, surface where a brake disc is mounted, of the wheel mounting flange 6 is primarily cut by turning.","An annular groove (circumferential groove) 7a is formed in the surface 7 with a predetermined width.","Bolt apertures 8 are formed in the annular groove 7a at center positions in the groove width direction equidistantly along the annular groove 7a.","The side surface 7 is secondarily cut by turning after knurled portions 9 of the hub bolts 6a have been press-fit into the bolt apertures 8.The secondary cut may be performed by other cutting using a milling machine or grinding machine.","The wheel hub 1 is made of medium-high carbon steel such as S53C including carbon of 0.40˜0.80% by weight.","It is hardened by high frequency induction hardening to have a surface hardness of 50˜64 HRC over the inner raceway surface 1a and a region from an inner-side base 6b of the wheel mounting flange 6, forming a seal land portion of a seal 10, to the cylindrical portion 1b.","The caulked portion 1d is not hardened and is kept with a hardness after forging.","This not only improves the anti-friction property of the base portion 6b of the wheel mounting flange 6 but applies sufficient mechanical strength against a rotary bending load loaded on the wheel mounting flange 6.In addition, it is possible to improve the anti-fretting property of the cylindrical portion 1b where the inner ring 2 is press-fit and perform the caulking process of the caulked portion id without causing any micro cracks.","The inner ring 2 is formed from high carbon chrome steel such as SUJ2.It is hardened to its core to have a hardness of 58˜64 HRC.","The rolling elements (balls) 4 are formed of high carbon chrome steel such as SUJ2.They are dip hardened to their cores to have a hardness of 62˜67 HRC.","The outer member 5 is formed, on its outer circumference, with a body mounting flange 5b.","The body mounting flange 5b is adapted to mount onto a knuckle (not shown) to form part of the suspension.","The outer member inner circumference includes double row outer raceway surfaces 5a, 5a that oppose the inner raceway surfaces 1a, 2a of the inner member 3.The double row rolling elements 4, 4 are rollably contained between the inner and outer raceway surfaces 1a, 2a and 5a, 5a, via cages 12.The outer member 5 is formed of medium-high carbon steel such as S53C including carbon of 0.40˜0.80% by weight.","At least the outer raceway surfaces 5a, 5a are hardened by high frequency induction hardening to have a surface hardness of 58˜64 HRC.","Seals 10, 11 are arranged at annular side openings formed between the outer member 5 and the inner member 3.The seals 10, 11 prevent lubricating grease, filled in the bearing, from leaking outside and rain water or dust from entry into the bearing from the outside.","Although the wheel bearing apparatus is shown here formed by a double row angular contact ball bearing using balls as rolling elements 4, the present disclosure is not limited to such a bearing.","Double row tapered roller bearings using tapered rollers as the rolling elements 4 may be used.","In addition, although it is shown here on the third generation type bearing, the present disclosure can be applied to a second generation type bearing, with a pair of inner rings press-fit onto the cylindrical portion, or a fourth generation type bearing, where the inner raceway surfaces are directly formed on the outer circumferences, respectively, of a wheel hub and an outer joint member of a constant velocity universal joint (not shown).","As shown in FIG.","2, a reinforcing rib 21 is formed, in a region where the hub bolt 6a is secured, as a build-up part on the inner-side surface of the wheel mounting flange 6.Each reinforcing rib 21 has a width substantially same as a formation part of each bolt aperture 8.The rib 21 extends radially outward from the annular base 6b of the wheel mounting flange 6 (see FIG.","1).","When the width of the annular groove 7a formed on the outer-side surface 7 of the wheel mounting flange 6 is larger, it is preferable that the workability of the secondary cutting of the side surface 7 occur after press-fitting of hub bolts 6a.","However, it is believed that the contact area between the side surface of the brake rotor and the side surface 7 of the wheel mounting flange would be reduced and the strength and rigidity of the wheel mounting flange 6 would be reduced.","Thus, the wheel mounting flange would be deformed by fastening of the nuts.","In this embodiment, if a distance from the outer diameter of each hub bolt 6a to the annular groove 7a is set at least 1 mm, it has been found that the contact area between the brake rotor and the wheel mounting flange 6 is not largely reduced and the deformation of the wheel mounting flange during fastening of a wheel by nuts can be suppressed.","Thus, worsening of the accuracy of the plane deflection of the side surface of the brake rotor can be limited to minimum.","In this case, when a space more than 1 mm from the outer diameter of each hub bolt 6a remains, workability of the cutting operation using a bite will not be worsened without interference of the bite and hub bolts 6a.","As described above, the deformation of the outer-side surface 7 caused by press-fitting of hub bolts 6a will be limited to a minimum by forming the annular groove 7a on the side surface 7 of the wheel mounting flange 6.In addition, if secondary cutting is performed on the outer-side surface 7 where the brake rotor contacts, the plane deflection that would be caused by press-fitting of the hub bolts 6a will be substantially reduced.","Thus, the generation of brake judder will be suppressed by enhancing the accuracy of the plane deflection of the wheel mounting flange 6.Although the present disclosure has been described with reference to an embodiment where the primary cutting of the outside-surface 7 of the wheel mounting flange 6 is previously performed before press-fitting the hub bolts 6a and then secondary cutting is performed after press-fitting of the hub bolts 6a, the present disclosure is not limited to such an embodiment.","For example, it may be possible to perform primary cutting, via rough turning and semi-finish turning, before press-fitting of the hub bolts 6a.","Secondary cutting (finish turning) would be performed after press-fitting of the hub bolts 6a.","In addition, it may be possible to omit the turning before press-fitting of the hub bolts 6a while remaining in a forged skin state and perform secondary cutting (finish turning) after press-fitting of the hub bolts 6a.","Circular apertures (weight reduction apertures) 13 are formed, by forging, between the hub bolts 6a of the wheel mounting flange 6 equidistantly along a desired diameter of the flange.","The weight reduction apertures 13 are formed beyond the outer diameter of the annular groove 7a.","That is, when a diameter of a circle circumscribing the weight reduction apertures 13 is defined as “A” and an outer diameter of the annular groove 7a is defined as “B”, it is set so that A>B.","Accordingly, as shown in an enlarged view of FIG.","3, such an arrangement of the weight reduction apertures 13 and the annular groove 7a enables muddy water etc.","entering into the weight reduction apertures 13 to be easily discharge through the weight reduction apertures 13 as shown by an arrow in FIG.","3 without remaining in a clearance between the side surface 7 of the wheel mounting flange 6 and the side surface 14a of the brake disc 14.Thus, it is possible to provide a wheel bearing apparatus that reduces its own weight and improves reliability while enhancing the accuracy of the plane deflection of the wheel mounting flange 6 and thus suppresses the generation of brake judder.","FIG.","4 shows modified circular apertures i.e.","weight reduction apertures 15 of the previously described ones.","Similarly to the weight reduction apertures 13 of first embodiment, the diameter “A” of a circle circumscribing the weight reduction apertures 15 is larger than the outer diameter “B” of the annular groove 7a, as shown in FIG.","4(a).","In this modification, an inner circumferential surface of each of the weight reduction apertures 15 is tapered.","The taper is on an inclined angle 0 gradually expanding toward the inner-side of the wheel mounting flange 6 as shown in FIG.","4(b).","Accordingly, it is possible to more easily discharge muddy water etc.","from the weight reduction apertures 15 while preventing the muddy water etc.","from remaining in a clearance between the side surface 7 of the wheel mounting flange 6 and the side surface 14a of the brake disc 14.FIG.","5 shows another modification of the previously described weight reduction apertures 13.The weight reduction apertures 16 of this modification are formed so that they are arranged at positions radially inside of the outer diameter of the annular groove 7a as shown in FIG.","5(a).","That is, the diameter “C” of a circle circumscribing the weight reduction apertures 16 is smaller than the outer diameter “B” of the annular groove 7a (C1.5 PCDb, the weight reduction effect brought by the cut-off parts 22 could not be expected.","In general, such a wheel hub is formed by hot forging.","The wheel mounting flange has a flower-shape and its material between the bolt apertures 8 is insufficient.","It is usually necessary to protrude excessive forged material between tools (punch and/or die) as burrs in order to improve the accuracy of forging when the wheel hub is formed by a so-called closed forging method where upset parts of the wheel hub are restricted.","However, in the wheel hub 18 of this embodiment, since the cut-off parts 22 are positioned outside of the PCDb of the bolt apertures and sufficient material is present between the bolt apertures 8, it is possible to perform the forging process efficiently and accurately without obstructing plastic flow of the material.","Accordingly, corner portions, stepped portions and chamfered portions of material can be perfectly formed by the closed forging method.","Thus, removal of burrs can be limited to minimum.","Thus, it is possible to reduce manufacturing cost by the reduction of manufacturing steps.","Similarly to the previously described embodiment, the annular groove 23a is formed on the outer-side surface 23 of the wheel mounting flange 20.The annular groove 23a has a discontinuous shape since the wheel mounting flange 20 has a flower-shape not a circular shape of the previous wheel mounting flange 6.The bolt apertures 8 are formed at the center of both the groove width of the annular groove 23a and the hub bolts 6a equidistantly along the annular groove 23a.","The secondary cutting of the side surface 23 is performed by turning after press-fitting of the hub bolts 6a into the bolt apertures 8.The weight reduction apertures (circular apertures) 24 are formed by forging equidistantly along a desired diameter of the wheel mounting flange 20, between the hub bolts 6a.","The weight reduction apertures 24 are positioned radially inside of the outer diameter of the annular groove 23a.","That is, a diameter D of the deepest portions 22a of the cut-off parts 22 is smaller than an outer diameter B of the annular groove 23a (D BACKGROUND In general, disc brakes are superior in braking performance and have become very popular.\",\n \"However, a problem exists in that the disc brakes cause vibrations and thus uncomfortable noise at low frequency especially at low speed traveling when braking, sandwiching a brake rotor between brake pads.\",\n \"Such a phenomenon is called brake judder.\",\n \"It has been recently noticed as a new subject in technology requiring analysis and improvement due to a desire to achieve high performance as well as silence in the vehicle.\",\n \"Although theoretical mechanisms causing brake judder have not been found yet, it is believed that one factor is the accuracy of plane deflection of a pad sliding surface.\",\n \"The accuracy of plane deflection appears as a plane deflection of a side surface of the brake rotor due to accumulation of not only the plane deflection accuracies of the brake rotor itself but the wheel mounting flange on which the brake rotor is mounted, axial deflection of the rolling bearings, accuracy of the inner or outer raceway surfaces and the assembling accuracy of the rolling bearings.\",\n \"In recent years, measures, for the plane deflection accuracy of the side surface of brake rotor described above, have been taken with satisfying conflicting demands of reduction of size and weight of the wheel bearing apparatus.\",\n \"This improves fuel consumption and increases the rigidity of the wheel bearing apparatus to improve driving stability of the vehicle.\",\n \"One example of a known wheel bearing apparatus is shown in FIG.\",\n \"7 .\",\n \"This wheel bearing apparatus has an inner member 50 , an outer member 60 and double row rolling elements 70 , 70 .\",\n \"The inner member 50 has a wheel hub 51 and an inner ring 52 press-fit onto a cylindrical portion 53 of the wheel hub 51 .\",\n \"One inner raceway surface 51 a is formed on the outer circumference of the wheel hub 51 .\",\n \"The other inner raceway surface 52 a is formed on the outer circumference of the inner ring 52 .\",\n \"The wheel hub 51 is integrally formed, on its outer-side end, with a wheel mounting flange 54 to mount a wheel (not shown).\",\n \"Hub bolts 55 are mounted equidistantly on the wheel mounting flange 54 .\",\n \"On the other hand, the outer member 60 is formed, on its outer circumference, with a body mounting flange 61 adapted to be mounted on a body (not shown) of a vehicle.\",\n \"The outer member inner circumference includes double row outer raceway surfaces 60 a , 60 a .\",\n \"The double row rolling elements (balls) 70 , 70 are rollably accommodated between the inner and outer raceway surfaces 51 a , 52 a and 60 a , 60 a , via cages 71 , 71 .\",\n \"Seals 62 , 63 are mounted on both end of the outer member 60 to seal annular spaces between the outer member 60 and the inner member 50 .\",\n \"This prevents leakage of lubricating grease confined within the bearing and entry of rain water or dust from the outside into the bearing.\",\n \"An annular groove 56 is formed on the outer-side surface 54 a of the wheel mounting flange 54 .\",\n \"Bolt apertures 57 are formed equidistantly along and in the annular groove 56 .\",\n \"The hub bolts 55 are secured in the bolt apertures 57 by press-fitting knurled portions 55 a of the hub bolts 55 into the bolt apertures 57 .\",\n \"A wheel is adapted to be secured on the wheel mounting flange 54 , via the brake rotor (not shown), by fastening nuts (not shown) onto the hub bolts 55 .\",\n \"The outer-side surface 54 a of the wheel mounting flange 54 is finished processed by grinding after press-fitting of the hub bolts 55 .\",\n \"This enables the deformation around the bolt aperture 57 or undulations of the side surface 54 a generated by forming the bolt apertures 57 in the annular groove 56 and press-fitting the hub bolts 55 to mainly occur within the annular groove 56 as well as to suppress the influences to the accuracy of plane deflection of the side surface 54 a caused by press-fitting of the hub bolts 55 to substantially zero.\",\n \"See, JP2003-154801 A.\",\n \"However, in the prior art wheel bearing apparatus, when circular apertures (weight reduction apertures) 80 are formed between the hub bolts 55 , as shown in FIG.\",\n \"8( a ) , muddy water etc.\",\n \"that enters through the weight reduction apertures 80 and often remains in a clearance between the outer-side surface 54 a of the wheel mounting flange 54 and a side surface 81 a of the brake rotor 81 .\",\n \"Thus, rusts is generated on the contact surfaces between the two.\",\n \"As a result, the accuracy of the plane deflection of the side surface 54 a of the wheel mounting flange 54 becomes worse.\",\n \"Thus, it is believed that brake judder would be caused as well as the brake rotor 81 strongly fixed to the wheel mounting flange 54 , via rust.\",\n \"Thus, disassembly of the brake rotor 81 from the wheel mounting flange 54 would be difficult.\",\n \"The present disclosure has been achieved with focus on a structure that easily discharges muddy water etc.\",\n \"entering through the weight reduction apertures of the wheel mounting flange while preventing the muddy water etc.\",\n \"from remaining in a clearance space between the wheel mounting flange and the brake rotor.\",\n \"Thus, it is an object of the present disclosure to provide a wheel bearing apparatus that reduces its weight and improves reliability while enhancing the accuracy of the plane deflection of the wheel mounting flange and thus suppressing the generation of brake judder.\"\n ],\n [\n \" SUMMARY To achieve the above objects, a wheel bearing apparatus comprises an outer member, an inner member and double row rolling elements.\",\n \"The outer member includes double row outer raceway surfaces on its inner circumference.\",\n \"The inner member outer circumference includes double row inner raceway surfaces.\",\n \"The inner raceway surfaces oppose the double row outer raceway surfaces.\",\n \"The double row rolling elements are rollably accommodated in a space between the inner raceway surfaces of the inner member and the outer raceway surfaces of the outer member.\",\n \"A wheel mounting flange, for mounting a wheel via a brake disc, is mounted on a rotary-side of one of the outer member or the inner member.\",\n \"Hub bolts, for fastening the wheel, are secured equidistantly along the wheel mounting flange.\",\n \"An annular groove is formed on the outer-side surface of the wheel mounting flange.\",\n \"The annular groove includes a region where the hub bolts are mounted.\",\n \"Weight reduction apertures are formed between the hub bolts of the wheel mounting flange.\",\n \"A diameter of a circumscribed circle circumscribing the weight reduction apertures is set larger than an outer diameter of the annular groove or the weight reduction apertures are opened to an outer circumferential surface of the wheel mounting flange.\",\n \"The wheel bearing apparatus has a wheel mounting flange, to mount a wheel via a brake disc, mounted on a rotary-side of one of the outer member or the inner member.\",\n \"Hub bolts, to fasten the wheel, are secured equidistantly along the wheel mounting flange.\",\n \"An annular groove is formed on the outer-side surface of the wheel mounting flange.\",\n \"The annular groove includes a region where the hub bolts are mounted.\",\n \"Weight reduction apertures are formed between hub bolts on the wheel mounting flange.\",\n \"A diameter of a circumscribed circle circumscribing the weight reduction apertures is set larger than an outer diameter of the annular groove or the weight reduction apertures are opened to an outer circumferential surface of the wheel mounting flange.\",\n \"Thus, it is possible to provide a wheel bearing apparatus that easily discharges muddy water etc.\",\n \"entering into the weight reduction apertures of the wheel mounting flange while preventing the muddy water etc.\",\n \"from remaining in a clearance gap between the outer-side surface of the wheel mounting flange and the side surface of the brake disc.\",\n \"The wheel bearing apparatus can reduce its own weight and improve reliability while enhancing the accuracy of the plane deflection of the wheel mounting flange and thus suppress the generation of brake judder.\",\n \"The outer-side surface of the wheel mounting flange is formed as a cut surface.\",\n \"It is cut after press-fitting of the hub bolts.\",\n \"This makes it possible to achieve the finish process by a simple turning process and thus reduce the manufacturing cost.\",\n \"In addition, it is possible to suppress the generation of brake judder while enhancing the accuracy of the plane deflection of the wheel mounting flange by reducing influences on the plane deflection due to press-fitting of hub bolts.\",\n \"Each of the weight reduction apertures in the wheel mounting flange is formed as a tapered aperture gradually expanding toward the inner-side.\",\n \"This makes it possible to easily discharge muddy water etc.\",\n \"from the weight reduction apertures while preventing the muddy water etc.\",\n \"from remaining in a clearance space between the wheel mounting flange and the brake disc.\",\n \"Radially extending drain grooves are formed by cutting a portion of each weight reduction aperture of the wheel mounting flange.\",\n \"This makes it possible to easily discharge muddy water etc.\",\n \"from the weight reduction apertures through the drain grooves even though the weight reduction apertures are formed within a region of the annular groove.\",\n \"This prevents the muddy water etc.\",\n \"from remaining in a clearance gap between the wheel mounting flange and the brake disc.\",\n \"A radially extending reinforcing rib is formed, as a build-up part, on the inner-side surface of the wheel mounting flange.\",\n \"It is formed in a region where the hub bolt is secured.\",\n \"This makes it possible to reduce the weight of the wheel mounting flange while keeping its strength and rigidity.\",\n \"Cut-off parts are formed on the outer circumference of the wheel mounting flange between the bolt apertures.\",\n \"The hub bolts are press-fit into the aperture while keeping clear or near the bolt apertures.\",\n \"Each of the cut-off parts are formed with a circular arc shape so that the deepest portions of the cut-off parts are positioned in proximity to a pitch circle diameter of the bolt apertures.\",\n \"This makes it possible to reduce the weight and size of the wheel mounting flange while keeping its strength and rigidity.\",\n \"Also, it suppresses the generation of brake judder while enhancing the accuracy of the plane deflection of the wheel mounting flange by reducing deformation of the wheel mounting flange due to its heat treatment.\",\n \"A diameter of the deepest portions of the cut-off parts is smaller than an outer diameter of the annular groove.\",\n \"This makes it possible to make the weight reduction apertures open to the outer circumference of the wheel mounting flange.\",\n \"Accordingly, it is possible to easily discharge muddy water etc.\",\n \"entering into the weight reduction apertures of the wheel mounting flange through the deepest portions of the cut-off parts.\",\n \"This prevents the muddy water etc.\",\n \"from remaining in a clearance space between the wheel mounting flange and the brake disc.\",\n \"This also reduces the wheel bearing assembly's own weight and improves reliability while enhancing the accuracy of the plane deflection of the wheel mounting flange and thus suppresses the generation of brake judder.\",\n \"The wheel bearing apparatus has an outer member, inner member and double row rolling elements.\",\n \"The outer member inner circumference includes double row outer raceway surfaces.\",\n \"The inner member outer circumferences include double row inner raceway surfaces opposing the double row outer raceway surfaces.\",\n \"The double row rolling elements are rollably accommodated in a space between the inner raceway surfaces of the inner member and the outer raceway surfaces of the outer member.\",\n \"A wheel mounting flange, to mount a wheel via a brake disc, is mounted on a rotary-side of one of the outer member or the inner member.\",\n \"Hub bolts, to fasten the wheel, are secured equidistantly along the wheel mounting flange.\",\n \"An annular groove is formed on the outer-side surface of the wheel mounting flange.\",\n \"The annular groove has a region where the hub bolts are mounted.\",\n \"Weight reduction apertures are formed between hub bolts of the wheel mounting flange.\",\n \"A diameter of a circumscribed circle circumscribing the weight reduction apertures is set larger than an outer diameter of the annular groove or the weight reduction apertures are opened to an outer circumferential surface of the wheel mounting flange.\",\n \"Thus, it is possible to provide a wheel bearing apparatus that can easily discharge muddy water etc.\",\n \"entering into the weight reduction apertures of the wheel mounting flange while preventing the muddy water etc.\",\n \"from remaining in a clearance space between the wheel mounting flange and the brake disc.\",\n \"This also reduces the wheel bearing assembly's own weight and improves reliability while enhancing the accuracy of the plane deflection of the wheel mounting flange and thus suppress the generation of brake judder.\",\n \"Further areas of applicability will become apparent from the description provided herein.\",\n \"The description and specific examples in this summary are intended for purposes of illustration only and are not intended to limit the scope of the present disclosure.\"\n ],\n [\n \"CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of International Application No.\",\n \"PCT/JP2016/070914, filed Jul.\",\n \"14, 2016, which claims priority to Japanese Application No.\",\n \"2015-141921, filed Jul.\",\n \"16, 2015.The disclosures of the above applications are incorporating herein by reference.\",\n \"FIELD The present disclosure relates to a wheel bearing apparatus that rotationally bears the weight of a vehicle wheel, such as an automobile, and, more particularly, to a wheel bearing apparatus that reduces the weight of the wheel bearing apparatus as well as suppress the generation of brake judder while enhancing the accuracy of the plane deflection of a wheel mounting flange.\",\n \"Thus, this improves the reliability of the wheel bearing apparatus.\",\n \"BACKGROUND In general, disc brakes are superior in braking performance and have become very popular.\",\n \"However, a problem exists in that the disc brakes cause vibrations and thus uncomfortable noise at low frequency especially at low speed traveling when braking, sandwiching a brake rotor between brake pads.\",\n \"Such a phenomenon is called brake judder.\",\n \"It has been recently noticed as a new subject in technology requiring analysis and improvement due to a desire to achieve high performance as well as silence in the vehicle.\",\n \"Although theoretical mechanisms causing brake judder have not been found yet, it is believed that one factor is the accuracy of plane deflection of a pad sliding surface.\",\n \"The accuracy of plane deflection appears as a plane deflection of a side surface of the brake rotor due to accumulation of not only the plane deflection accuracies of the brake rotor itself but the wheel mounting flange on which the brake rotor is mounted, axial deflection of the rolling bearings, accuracy of the inner or outer raceway surfaces and the assembling accuracy of the rolling bearings.\",\n \"In recent years, measures, for the plane deflection accuracy of the side surface of brake rotor described above, have been taken with satisfying conflicting demands of reduction of size and weight of the wheel bearing apparatus.\",\n \"This improves fuel consumption and increases the rigidity of the wheel bearing apparatus to improve driving stability of the vehicle.\",\n \"One example of a known wheel bearing apparatus is shown in FIG.\",\n \"7.This wheel bearing apparatus has an inner member 50, an outer member 60 and double row rolling elements 70, 70.The inner member 50 has a wheel hub 51 and an inner ring 52 press-fit onto a cylindrical portion 53 of the wheel hub 51.One inner raceway surface 51a is formed on the outer circumference of the wheel hub 51.The other inner raceway surface 52a is formed on the outer circumference of the inner ring 52.The wheel hub 51 is integrally formed, on its outer-side end, with a wheel mounting flange 54 to mount a wheel (not shown).\",\n \"Hub bolts 55 are mounted equidistantly on the wheel mounting flange 54.On the other hand, the outer member 60 is formed, on its outer circumference, with a body mounting flange 61 adapted to be mounted on a body (not shown) of a vehicle.\",\n \"The outer member inner circumference includes double row outer raceway surfaces 60a, 60a.\",\n \"The double row rolling elements (balls) 70, 70 are rollably accommodated between the inner and outer raceway surfaces 51a, 52a and 60a, 60a, via cages 71, 71.Seals 62, 63 are mounted on both end of the outer member 60 to seal annular spaces between the outer member 60 and the inner member 50.This prevents leakage of lubricating grease confined within the bearing and entry of rain water or dust from the outside into the bearing.\",\n \"An annular groove 56 is formed on the outer-side surface 54a of the wheel mounting flange 54.Bolt apertures 57 are formed equidistantly along and in the annular groove 56.The hub bolts 55 are secured in the bolt apertures 57 by press-fitting knurled portions 55a of the hub bolts 55 into the bolt apertures 57.A wheel is adapted to be secured on the wheel mounting flange 54, via the brake rotor (not shown), by fastening nuts (not shown) onto the hub bolts 55.The outer-side surface 54a of the wheel mounting flange 54 is finished processed by grinding after press-fitting of the hub bolts 55.This enables the deformation around the bolt aperture 57 or undulations of the side surface 54a generated by forming the bolt apertures 57 in the annular groove 56 and press-fitting the hub bolts 55 to mainly occur within the annular groove 56 as well as to suppress the influences to the accuracy of plane deflection of the side surface 54a caused by press-fitting of the hub bolts 55 to substantially zero.\",\n \"See, JP2003-154801 A.\",\n \"However, in the prior art wheel bearing apparatus, when circular apertures (weight reduction apertures) 80 are formed between the hub bolts 55, as shown in FIG.\",\n \"8(a), muddy water etc.\",\n \"that enters through the weight reduction apertures 80 and often remains in a clearance between the outer-side surface 54a of the wheel mounting flange 54 and a side surface 81a of the brake rotor 81.Thus, rusts is generated on the contact surfaces between the two.\",\n \"As a result, the accuracy of the plane deflection of the side surface 54a of the wheel mounting flange 54 becomes worse.\",\n \"Thus, it is believed that brake judder would be caused as well as the brake rotor 81 strongly fixed to the wheel mounting flange 54, via rust.\",\n \"Thus, disassembly of the brake rotor 81 from the wheel mounting flange 54 would be difficult.\",\n \"The present disclosure has been achieved with focus on a structure that easily discharges muddy water etc.\",\n \"entering through the weight reduction apertures of the wheel mounting flange while preventing the muddy water etc.\",\n \"from remaining in a clearance space between the wheel mounting flange and the brake rotor.\",\n \"Thus, it is an object of the present disclosure to provide a wheel bearing apparatus that reduces its weight and improves reliability while enhancing the accuracy of the plane deflection of the wheel mounting flange and thus suppressing the generation of brake judder.\",\n \"SUMMARY To achieve the above objects, a wheel bearing apparatus comprises an outer member, an inner member and double row rolling elements.\",\n \"The outer member includes double row outer raceway surfaces on its inner circumference.\",\n \"The inner member outer circumference includes double row inner raceway surfaces.\",\n \"The inner raceway surfaces oppose the double row outer raceway surfaces.\",\n \"The double row rolling elements are rollably accommodated in a space between the inner raceway surfaces of the inner member and the outer raceway surfaces of the outer member.\",\n \"A wheel mounting flange, for mounting a wheel via a brake disc, is mounted on a rotary-side of one of the outer member or the inner member.\",\n \"Hub bolts, for fastening the wheel, are secured equidistantly along the wheel mounting flange.\",\n \"An annular groove is formed on the outer-side surface of the wheel mounting flange.\",\n \"The annular groove includes a region where the hub bolts are mounted.\",\n \"Weight reduction apertures are formed between the hub bolts of the wheel mounting flange.\",\n \"A diameter of a circumscribed circle circumscribing the weight reduction apertures is set larger than an outer diameter of the annular groove or the weight reduction apertures are opened to an outer circumferential surface of the wheel mounting flange.\",\n \"The wheel bearing apparatus has a wheel mounting flange, to mount a wheel via a brake disc, mounted on a rotary-side of one of the outer member or the inner member.\",\n \"Hub bolts, to fasten the wheel, are secured equidistantly along the wheel mounting flange.\",\n \"An annular groove is formed on the outer-side surface of the wheel mounting flange.\",\n \"The annular groove includes a region where the hub bolts are mounted.\",\n \"Weight reduction apertures are formed between hub bolts on the wheel mounting flange.\",\n \"A diameter of a circumscribed circle circumscribing the weight reduction apertures is set larger than an outer diameter of the annular groove or the weight reduction apertures are opened to an outer circumferential surface of the wheel mounting flange.\",\n \"Thus, it is possible to provide a wheel bearing apparatus that easily discharges muddy water etc.\",\n \"entering into the weight reduction apertures of the wheel mounting flange while preventing the muddy water etc.\",\n \"from remaining in a clearance gap between the outer-side surface of the wheel mounting flange and the side surface of the brake disc.\",\n \"The wheel bearing apparatus can reduce its own weight and improve reliability while enhancing the accuracy of the plane deflection of the wheel mounting flange and thus suppress the generation of brake judder.\",\n \"The outer-side surface of the wheel mounting flange is formed as a cut surface.\",\n \"It is cut after press-fitting of the hub bolts.\",\n \"This makes it possible to achieve the finish process by a simple turning process and thus reduce the manufacturing cost.\",\n \"In addition, it is possible to suppress the generation of brake judder while enhancing the accuracy of the plane deflection of the wheel mounting flange by reducing influences on the plane deflection due to press-fitting of hub bolts.\",\n \"Each of the weight reduction apertures in the wheel mounting flange is formed as a tapered aperture gradually expanding toward the inner-side.\",\n \"This makes it possible to easily discharge muddy water etc.\",\n \"from the weight reduction apertures while preventing the muddy water etc.\",\n \"from remaining in a clearance space between the wheel mounting flange and the brake disc.\",\n \"Radially extending drain grooves are formed by cutting a portion of each weight reduction aperture of the wheel mounting flange.\",\n \"This makes it possible to easily discharge muddy water etc.\",\n \"from the weight reduction apertures through the drain grooves even though the weight reduction apertures are formed within a region of the annular groove.\",\n \"This prevents the muddy water etc.\",\n \"from remaining in a clearance gap between the wheel mounting flange and the brake disc.\",\n \"A radially extending reinforcing rib is formed, as a build-up part, on the inner-side surface of the wheel mounting flange.\",\n \"It is formed in a region where the hub bolt is secured.\",\n \"This makes it possible to reduce the weight of the wheel mounting flange while keeping its strength and rigidity.\",\n \"Cut-off parts are formed on the outer circumference of the wheel mounting flange between the bolt apertures.\",\n \"The hub bolts are press-fit into the aperture while keeping clear or near the bolt apertures.\",\n \"Each of the cut-off parts are formed with a circular arc shape so that the deepest portions of the cut-off parts are positioned in proximity to a pitch circle diameter of the bolt apertures.\",\n \"This makes it possible to reduce the weight and size of the wheel mounting flange while keeping its strength and rigidity.\",\n \"Also, it suppresses the generation of brake judder while enhancing the accuracy of the plane deflection of the wheel mounting flange by reducing deformation of the wheel mounting flange due to its heat treatment.\",\n \"A diameter of the deepest portions of the cut-off parts is smaller than an outer diameter of the annular groove.\",\n \"This makes it possible to make the weight reduction apertures open to the outer circumference of the wheel mounting flange.\",\n \"Accordingly, it is possible to easily discharge muddy water etc.\",\n \"entering into the weight reduction apertures of the wheel mounting flange through the deepest portions of the cut-off parts.\",\n \"This prevents the muddy water etc.\",\n \"from remaining in a clearance space between the wheel mounting flange and the brake disc.\",\n \"This also reduces the wheel bearing assembly's own weight and improves reliability while enhancing the accuracy of the plane deflection of the wheel mounting flange and thus suppresses the generation of brake judder.\",\n \"The wheel bearing apparatus has an outer member, inner member and double row rolling elements.\",\n \"The outer member inner circumference includes double row outer raceway surfaces.\",\n \"The inner member outer circumferences include double row inner raceway surfaces opposing the double row outer raceway surfaces.\",\n \"The double row rolling elements are rollably accommodated in a space between the inner raceway surfaces of the inner member and the outer raceway surfaces of the outer member.\",\n \"A wheel mounting flange, to mount a wheel via a brake disc, is mounted on a rotary-side of one of the outer member or the inner member.\",\n \"Hub bolts, to fasten the wheel, are secured equidistantly along the wheel mounting flange.\",\n \"An annular groove is formed on the outer-side surface of the wheel mounting flange.\",\n \"The annular groove has a region where the hub bolts are mounted.\",\n \"Weight reduction apertures are formed between hub bolts of the wheel mounting flange.\",\n \"A diameter of a circumscribed circle circumscribing the weight reduction apertures is set larger than an outer diameter of the annular groove or the weight reduction apertures are opened to an outer circumferential surface of the wheel mounting flange.\",\n \"Thus, it is possible to provide a wheel bearing apparatus that can easily discharge muddy water etc.\",\n \"entering into the weight reduction apertures of the wheel mounting flange while preventing the muddy water etc.\",\n \"from remaining in a clearance space between the wheel mounting flange and the brake disc.\",\n \"This also reduces the wheel bearing assembly's own weight and improves reliability while enhancing the accuracy of the plane deflection of the wheel mounting flange and thus suppress the generation of brake judder.\",\n \"Further areas of applicability will become apparent from the description provided herein.\",\n \"The description and specific examples in this summary are intended for purposes of illustration only and are not intended to limit the scope of the present disclosure.\",\n \"DRAWINGS The drawings described herein are for illustrative purposes only of selected embodiments and not all possible implementations, and are not intended to limit the scope of the present disclosure.\",\n \"FIG.\",\n \"1 is a longitudinal section view of a first embodiment of the wheel bearing apparatus of the present disclosure.\",\n \"FIG.\",\n \"2 is a side elevation view of a wheel hub of FIG.\",\n \"1.FIG.\",\n \"3 is a partially enlarged view of a weight reduction aperture of FIG.\",\n \"1.FIG.\",\n \"4(a) is a side elevation view of one modification of FIG.\",\n \"1.FIG.\",\n \"4(b) is a partially enlarged view of a weight reduction aperture of FIG.\",\n \"4(a).\",\n \"FIG.\",\n \"5(a) is a side elevation view of another modification of FIG.\",\n \"1.FIG.\",\n \"5(b) is a partially enlarged view of a weight reduction aperture of FIG.\",\n \"5(a).\",\n \"FIG.\",\n \"6(a) is a side elevation view of a second embodiment of the wheel bearing apparatus.\",\n \"FIG.\",\n \"6(b) is a longitudinal section view of FIG.\",\n \"6(a).\",\n \"FIG.\",\n \"6(c) is a partially enlarged view of a weight reduction aperture of FIG.\",\n \"6(b).\",\n \"FIG.\",\n \"7(a) is a side elevation view of a prior art wheel bearing apparatus.\",\n \"FIG.\",\n \"7(b) is a longitudinal section view of FIG.\",\n \"7(a).\",\n \"FIG.\",\n \"8(a) is a side elevation view of a wheel bearing apparatus where weight reduction apertures are formed in a wheel mounting flange of FIG.\",\n \"7(a).\",\n \"FIG.\",\n \"8(b) is a partially enlarged view of a weight reduction aperture of FIG.\",\n \"8(a).\",\n \"DETAILED DESCRIPTION The present disclosure is a wheel bearing apparatus with an outer member, inner member and rolling members.\",\n \"The outer member outer circumference includes a body mounting flange to be mounted on a knuckle forming a suspension apparatus.\",\n \"The outer member inner circumference includes double row outer raceway surfaces.\",\n \"The inner member includes a wheel hub and an inner ring.\",\n \"The wheel hub is integrally formed, on its one end, with a wheel mounting flange.\",\n \"The wheel hub outer circumference includes an inner raceway surface opposing one of the double row outer raceway surfaces.\",\n \"A cylindrical portion axially extends from the inner raceway surface.\",\n \"The inner ring is press-fit onto the cylindrical portion of the wheel hub.\",\n \"The inner ring outer circumference includes an inner raceway surface opposing the other of the double row outer raceway surfaces.\",\n \"The double row rolling elements are rollably accommodated in a space between the inner raceway surfaces of the inner member and the outer raceway surfaces of the outer member.\",\n \"Hub bolts, to fasten a wheel mounted on the wheel mounting flange, are equidistantly position along the wheel mounting flange.\",\n \"An annular groove is formed on the outer-side surface of the wheel mounting flange.\",\n \"The annular groove includes a region where the hub bolts are mounted.\",\n \"The outer-side surface of the wheel mounting flange is formed as a cut surface, cut after press-fitting of the hub bolts.\",\n \"Weight reduction apertures are formed between hub bolts on the wheel mounting flange.\",\n \"A diameter of a circumscribed circle circumscribing the weight reduction apertures is set larger than an outer diameter of the annular groove.\",\n \"Embodiments will be described with reference to the accompanied drawings.\",\n \"FIG.\",\n \"1 is a longitudinal section view of a first embodiment of the wheel bearing apparatus.\",\n \"FIG.\",\n \"2 is a side elevation view of a wheel hub of FIG.\",\n \"1.FIG.\",\n \"3 is a partially enlarged view of a weight reduction aperture of FIG.\",\n \"1.FIG.\",\n \"4(a) is a side elevation view of one modification of FIG.\",\n \"1.FIG.\",\n \"4(b) is a partially enlarged view of a weight reduction aperture of FIG.\",\n \"4(a).\",\n \"FIG.\",\n \"5(a) is a side elevation view of another modification of FIG.\",\n \"1.FIG.\",\n \"5(b) is a partially enlarged view of a weight reduction aperture of FIG.\",\n \"5(a).\",\n \"In the description of this specification, an outer-side of a bearing apparatus, when it is mounted on a vehicle, is referred to as the “outer-side” (left-side in FIG.\",\n \"1(b)).\",\n \"An inner-side of a bearing apparatus, when it is mounted on a vehicle, is referred to as the “inner-side” (right-side in FIG.\",\n \"1(b)).\",\n \"The wheel bearing apparatus shown in FIG.\",\n \"1 is a so-called “third generation” type for a driving wheel.\",\n \"It includes an inner member 3 including a wheel hub 1 and an inner ring 2 press-fit onto the wheel hub 1.An outer member 5 is mounted on the inner member 3, via a double row rolling elements (balls) 4, 4.The wheel hub 1 is integrally formed, on its outer-side end, with a wheel mounting flange 6.The flange 6 mounts a wheel, via a brake disc or a brake drum (not shown).\",\n \"The wheel hub outer circumference includes one (outer-side) inner raceway surface 1a.\",\n \"A cylindrical portion 1b axially extends from the inner raceway surface 1a.\",\n \"A serration (or spline) 1c, for torque transmission, is formed on the inner circumference of the wheel hub 1.Hub bolts 6a are secured at circumferentially equidistant positions on the wheel mounting flange 6.The inner ring 2 is formed, on its outer circumference, with an inner raceway surface 2a.\",\n \"The inner ring 2 is press-fit, via a predetermined interference, onto the outer circumference of the cylindrical portion 1b of the wheel hub 1.The inner ring 2 is axially secured on the cylindrical portion 1b by a caulked portion 1d.\",\n \"The caulked portion 1d is formed by plastically deforming radially outward an end of the cylindrical portion 1b under a predetermined bearing pre-pressure.\",\n \"An outer-side surface 7, surface where a brake disc is mounted, of the wheel mounting flange 6 is primarily cut by turning.\",\n \"An annular groove (circumferential groove) 7a is formed in the surface 7 with a predetermined width.\",\n \"Bolt apertures 8 are formed in the annular groove 7a at center positions in the groove width direction equidistantly along the annular groove 7a.\",\n \"The side surface 7 is secondarily cut by turning after knurled portions 9 of the hub bolts 6a have been press-fit into the bolt apertures 8.The secondary cut may be performed by other cutting using a milling machine or grinding machine.\",\n \"The wheel hub 1 is made of medium-high carbon steel such as S53C including carbon of 0.40˜0.80% by weight.\",\n \"It is hardened by high frequency induction hardening to have a surface hardness of 50˜64 HRC over the inner raceway surface 1a and a region from an inner-side base 6b of the wheel mounting flange 6, forming a seal land portion of a seal 10, to the cylindrical portion 1b.\",\n \"The caulked portion 1d is not hardened and is kept with a hardness after forging.\",\n \"This not only improves the anti-friction property of the base portion 6b of the wheel mounting flange 6 but applies sufficient mechanical strength against a rotary bending load loaded on the wheel mounting flange 6.In addition, it is possible to improve the anti-fretting property of the cylindrical portion 1b where the inner ring 2 is press-fit and perform the caulking process of the caulked portion id without causing any micro cracks.\",\n \"The inner ring 2 is formed from high carbon chrome steel such as SUJ2.It is hardened to its core to have a hardness of 58˜64 HRC.\",\n \"The rolling elements (balls) 4 are formed of high carbon chrome steel such as SUJ2.They are dip hardened to their cores to have a hardness of 62˜67 HRC.\",\n \"The outer member 5 is formed, on its outer circumference, with a body mounting flange 5b.\",\n \"The body mounting flange 5b is adapted to mount onto a knuckle (not shown) to form part of the suspension.\",\n \"The outer member inner circumference includes double row outer raceway surfaces 5a, 5a that oppose the inner raceway surfaces 1a, 2a of the inner member 3.The double row rolling elements 4, 4 are rollably contained between the inner and outer raceway surfaces 1a, 2a and 5a, 5a, via cages 12.The outer member 5 is formed of medium-high carbon steel such as S53C including carbon of 0.40˜0.80% by weight.\",\n \"At least the outer raceway surfaces 5a, 5a are hardened by high frequency induction hardening to have a surface hardness of 58˜64 HRC.\",\n \"Seals 10, 11 are arranged at annular side openings formed between the outer member 5 and the inner member 3.The seals 10, 11 prevent lubricating grease, filled in the bearing, from leaking outside and rain water or dust from entry into the bearing from the outside.\",\n \"Although the wheel bearing apparatus is shown here formed by a double row angular contact ball bearing using balls as rolling elements 4, the present disclosure is not limited to such a bearing.\",\n \"Double row tapered roller bearings using tapered rollers as the rolling elements 4 may be used.\",\n \"In addition, although it is shown here on the third generation type bearing, the present disclosure can be applied to a second generation type bearing, with a pair of inner rings press-fit onto the cylindrical portion, or a fourth generation type bearing, where the inner raceway surfaces are directly formed on the outer circumferences, respectively, of a wheel hub and an outer joint member of a constant velocity universal joint (not shown).\",\n \"As shown in FIG.\",\n \"2, a reinforcing rib 21 is formed, in a region where the hub bolt 6a is secured, as a build-up part on the inner-side surface of the wheel mounting flange 6.Each reinforcing rib 21 has a width substantially same as a formation part of each bolt aperture 8.The rib 21 extends radially outward from the annular base 6b of the wheel mounting flange 6 (see FIG.\",\n \"1).\",\n \"When the width of the annular groove 7a formed on the outer-side surface 7 of the wheel mounting flange 6 is larger, it is preferable that the workability of the secondary cutting of the side surface 7 occur after press-fitting of hub bolts 6a.\",\n \"However, it is believed that the contact area between the side surface of the brake rotor and the side surface 7 of the wheel mounting flange would be reduced and the strength and rigidity of the wheel mounting flange 6 would be reduced.\",\n \"Thus, the wheel mounting flange would be deformed by fastening of the nuts.\",\n \"In this embodiment, if a distance from the outer diameter of each hub bolt 6a to the annular groove 7a is set at least 1 mm, it has been found that the contact area between the brake rotor and the wheel mounting flange 6 is not largely reduced and the deformation of the wheel mounting flange during fastening of a wheel by nuts can be suppressed.\",\n \"Thus, worsening of the accuracy of the plane deflection of the side surface of the brake rotor can be limited to minimum.\",\n \"In this case, when a space more than 1 mm from the outer diameter of each hub bolt 6a remains, workability of the cutting operation using a bite will not be worsened without interference of the bite and hub bolts 6a.\",\n \"As described above, the deformation of the outer-side surface 7 caused by press-fitting of hub bolts 6a will be limited to a minimum by forming the annular groove 7a on the side surface 7 of the wheel mounting flange 6.In addition, if secondary cutting is performed on the outer-side surface 7 where the brake rotor contacts, the plane deflection that would be caused by press-fitting of the hub bolts 6a will be substantially reduced.\",\n \"Thus, the generation of brake judder will be suppressed by enhancing the accuracy of the plane deflection of the wheel mounting flange 6.Although the present disclosure has been described with reference to an embodiment where the primary cutting of the outside-surface 7 of the wheel mounting flange 6 is previously performed before press-fitting the hub bolts 6a and then secondary cutting is performed after press-fitting of the hub bolts 6a, the present disclosure is not limited to such an embodiment.\",\n \"For example, it may be possible to perform primary cutting, via rough turning and semi-finish turning, before press-fitting of the hub bolts 6a.\",\n \"Secondary cutting (finish turning) would be performed after press-fitting of the hub bolts 6a.\",\n \"In addition, it may be possible to omit the turning before press-fitting of the hub bolts 6a while remaining in a forged skin state and perform secondary cutting (finish turning) after press-fitting of the hub bolts 6a.\",\n \"Circular apertures (weight reduction apertures) 13 are formed, by forging, between the hub bolts 6a of the wheel mounting flange 6 equidistantly along a desired diameter of the flange.\",\n \"The weight reduction apertures 13 are formed beyond the outer diameter of the annular groove 7a.\",\n \"That is, when a diameter of a circle circumscribing the weight reduction apertures 13 is defined as “A” and an outer diameter of the annular groove 7a is defined as “B”, it is set so that A>B.\",\n \"Accordingly, as shown in an enlarged view of FIG.\",\n \"3, such an arrangement of the weight reduction apertures 13 and the annular groove 7a enables muddy water etc.\",\n \"entering into the weight reduction apertures 13 to be easily discharge through the weight reduction apertures 13 as shown by an arrow in FIG.\",\n \"3 without remaining in a clearance between the side surface 7 of the wheel mounting flange 6 and the side surface 14a of the brake disc 14.Thus, it is possible to provide a wheel bearing apparatus that reduces its own weight and improves reliability while enhancing the accuracy of the plane deflection of the wheel mounting flange 6 and thus suppresses the generation of brake judder.\",\n \"FIG.\",\n \"4 shows modified circular apertures i.e.\",\n \"weight reduction apertures 15 of the previously described ones.\",\n \"Similarly to the weight reduction apertures 13 of first embodiment, the diameter “A” of a circle circumscribing the weight reduction apertures 15 is larger than the outer diameter “B” of the annular groove 7a, as shown in FIG.\",\n \"4(a).\",\n \"In this modification, an inner circumferential surface of each of the weight reduction apertures 15 is tapered.\",\n \"The taper is on an inclined angle 0 gradually expanding toward the inner-side of the wheel mounting flange 6 as shown in FIG.\",\n \"4(b).\",\n \"Accordingly, it is possible to more easily discharge muddy water etc.\",\n \"from the weight reduction apertures 15 while preventing the muddy water etc.\",\n \"from remaining in a clearance between the side surface 7 of the wheel mounting flange 6 and the side surface 14a of the brake disc 14.FIG.\",\n \"5 shows another modification of the previously described weight reduction apertures 13.The weight reduction apertures 16 of this modification are formed so that they are arranged at positions radially inside of the outer diameter of the annular groove 7a as shown in FIG.\",\n \"5(a).\",\n \"That is, the diameter “C” of a circle circumscribing the weight reduction apertures 16 is smaller than the outer diameter “B” of the annular groove 7a (C1.5 PCDb, the weight reduction effect brought by the cut-off parts 22 could not be expected.\",\n \"In general, such a wheel hub is formed by hot forging.\",\n \"The wheel mounting flange has a flower-shape and its material between the bolt apertures 8 is insufficient.\",\n \"It is usually necessary to protrude excessive forged material between tools (punch and/or die) as burrs in order to improve the accuracy of forging when the wheel hub is formed by a so-called closed forging method where upset parts of the wheel hub are restricted.\",\n \"However, in the wheel hub 18 of this embodiment, since the cut-off parts 22 are positioned outside of the PCDb of the bolt apertures and sufficient material is present between the bolt apertures 8, it is possible to perform the forging process efficiently and accurately without obstructing plastic flow of the material.\",\n \"Accordingly, corner portions, stepped portions and chamfered portions of material can be perfectly formed by the closed forging method.\",\n \"Thus, removal of burrs can be limited to minimum.\",\n \"Thus, it is possible to reduce manufacturing cost by the reduction of manufacturing steps.\",\n \"Similarly to the previously described embodiment, the annular groove 23a is formed on the outer-side surface 23 of the wheel mounting flange 20.The annular groove 23a has a discontinuous shape since the wheel mounting flange 20 has a flower-shape not a circular shape of the previous wheel mounting flange 6.The bolt apertures 8 are formed at the center of both the groove width of the annular groove 23a and the hub bolts 6a equidistantly along the annular groove 23a.\",\n \"The secondary cutting of the side surface 23 is performed by turning after press-fitting of the hub bolts 6a into the bolt apertures 8.The weight reduction apertures (circular apertures) 24 are formed by forging equidistantly along a desired diameter of the wheel mounting flange 20, between the hub bolts 6a.\",\n \"The weight reduction apertures 24 are positioned radially inside of the outer diameter of the annular groove 23a.\",\n \"That is, a diameter D of the deepest portions 22a of the cut-off parts 22 is smaller than an outer diameter B of the annular groove 23a (D BACKGROUND It is recognized that individual humans differ in their sequence and recently several individuals have had their genomes sequenced, for instance James Watson and Craig Venter.","Comparison of the genome sequence of individuals has revealed differences in their sequences in both coding and non-coding parts of the genome.","Some of these variations in humans are significant and contribute to phenotypic differences between individuals.","In extreme cases these will result in genetic disease.","The 1000 Genomes Project has the objective of cataloguing sequences in the human genome, involving sequencing the genomes of a very large sampling of individuals from diverse art-recognized human ethnic populations."],[" SUMMARY Through the application of human genetic variation analysis and rationally-designed sequence selection the present invention provides for improved human patient diagnosis and therapy.","Importantly, the invention enables tailored medicines that address individual human patient genotypes or phenotypes.","The inventor's analysis of large numbers of naturally-occurring genomic human TOI sequences reveals that there is significant variation across diverse human populations and provides for the ability for correlation between individual human patients and tailored medical and diagnostic approaches addressing the target.","The technical applications of these findings, as per the present invention, thus contribute to better treatment, prophylaxis and diagnosis in humans and provides for patient benefit by enabling personalized medicines and therapies.","This provides advantages of better prescribing, less wastage of medications and improved chances of drug efficacy and better diagnosis in patients.","Furthermore, the inventor surprisingly realised that some rarer natural forms, although present in humans at much lower frequencies than the common form, nevertheless are represented in multiple and ethnically-diverse human populations and usually with many human examples per represented ethnic population.","Thus, the inventor realised that targeting such rarer forms would provide for effective treatment, prophylaxis or diagnosis across many human ethnic populations, thereby extending the utility of the present invention and better serving patients in those populations.","With this, the inventor realised that there is significant industrial and medical application for the invention in terms of guiding the choice of an anti-TOI ligand for administration to human patients for therapy and/or prophylaxis of TOI-mediated or associated diseases and conditions.","In this way, the patient receives drugs and ligands that are tailored to their needs—as determined by the patient's genetic or phenotypic makeup.","Hand-in-hand with this, the invention provides for the genotyping and/or phenotyping of patients in connection with such treatment, thereby allowing a proper match of drug to patient.","This increases the chances of medical efficacy, reduces the likelihood of inferior treatment using drugs or ligands that are not matched to the patient (eg, poor efficacy and/or side-effects) and avoids pharmaceutical mis-prescription and waste.","To this end, the invention provides:— In a First Configuration A method of treating or preventing a disease or condition in a human, wherein the disease or condition is mediated by a Target of Interest (TOI), wherein the TOI is present in humans as different polymorphic variants, the method comprising a.","Administering to the human an anti-TOI ligand to target a TOI variant in the human and treat or prevent said disease or condition, wherein the TOI in said human is encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or wherein the TOI in said human is encoded by a nucleotide sequence having a total human genotype frequency of less than 50%; wherein b.","Before step (a) said human has been or is genotyped as positive for said nucleotide sequence or phenotyped as positive for said TOI variant.","In a Second Configuration A method of treating or preventing a disease or condition in a human, wherein the disease or condition is mediated by a Target of Interest (TOI), wherein the TOI is present in humans as different polymorphic variants, the method comprising a.","Administering to the human an anti-TOI ligand to target a TOI variant in the human and treat or prevent said disease or condition, wherein the TOI in said human is encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or wherein the TOI in said human is encoded by a nucleotide sequence having a total human genotype frequency of less than 50%; wherein b. before step (a) the ligand has been or is determined as capable of binding to said TOI variant.","In a Third Configuration A method of treating or preventing a disease or condition in a human, wherein the disease or condition is mediated by a Target of Interest (TOI), wherein the TOI is present in humans as different polymorphic variants, the method comprising a.","Administering to the human an anti-TOI ligand to target a TOI variant in the human and treat or prevent said disease or condition, wherein the TOI in said human is a variant encoded by a nucleotide sequence having a cumulative human allele frequency of more than 50% and/or having a total human genotype frequency of more than 50%; wherein b.","Before step (a) said human has been or is genotyped as negative for a variant nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%; or phenotyped as negative for a TOI variant encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.","In a Fourth Configuration An anti-human TOI ligand for use in a method of treating and/or preventing a TOI-mediated disease or condition in a human, wherein the TOI is present in humans as different polymorphic variants and wherein the genome of said human comprises a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, the method comprising administering the ligand to the human.","In a Fifth Configuration A ligand that binds a human TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, for use in a method comprising the step of using the ligand to target said TOI in a human to treat and/or prevent a disease or condition mediated by TOI, the method comprising administering the ligand to the human.","In a Sixth Configuration A pharmaceutical composition or kit for treating or preventing a condition or disease mediated by a TOI.","In a Seventh Configuration A method of producing an anti-human TOI antibody binding site, the method comprising obtaining a plurality of anti-TOI antibody binding sites, screening the antibody binding sites for binding to a TOI comprising an amino acid sequence encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, or to a peptide thereof that comprises an amino acid variation from the corresponding sequence encoded by the TOI-encoding nucleotide sequence having the highest cumulative human allele frequency and/or the highest total human genotype frequency, and isolating an antibody binding site that binds in the screening step.","In a Eighth Configuration A method of producing an anti-human TOI antibody, the method comprising immunising a non-human vertebrate (eg, a mouse or a rat) with a TOI comprising an amino acid sequence encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, or to a peptide thereof that comprises an amino acid variation from the corresponding sequence encoded by the TOI-encoding nucleotide sequence having the highest cumulative human allele frequency and/or the highest total human genotype frequency, and isolating an antibody that binds a TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, and optionally producing a TOI-binding fragment or derivative of the isolated antibody.","In a Ninth Configuration A kit for TOI genotyping a human, wherein the kit comprises a nucleic acid comprising a nucleotide sequence that specifically hybridises to a TOI nucleotide sequence selected having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50% or an RNA transcript thereof; and/or the nucleic acid comprises a nucleotide sequence that comprises at least 10 contiguous nucleotides of a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50% or is an antisense sequence thereof.","In a Tenth Configuration Use of an anti-TOI ligand that binds a human TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, in the manufacture of a medicament for treating and/or preventing a TOI-mediated disease or condition in a human whose genome comprises a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.","In a Eleventh Configuration Use of an anti-TOI ligand that binds a human TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, in the manufacture of a medicament for targeting said TOI in a human to treat and/or prevent a disease or condition mediated by TOI.","In a Twelfth Configuration A method of targeting a TOI for treating and/or preventing a TOI-mediated disease or condition in a human, the method comprising administering an anti-TOI ligand to a human comprising a TOI nucleotide sequence selected having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, whereby a TOI encoded by said nucleotide sequence is targeted.","In a Thirteenth Configuration A method of TOI genotyping a nucleic acid sample of a human, the method comprising identifying in the sample the presence of a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.","In a Fourteenth Configuration A method of TOI typing a protein sample of a human, the method comprising identifying in the sample the presence of a TOI amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.","In an example, the TOI is a human TOI selected from the group consisting of PCSK9, VEGF-A and IL6 receptor.","A Fifteenth Configuration provides a ligand, method, use, kit or composition of the invention, wherein (i) the ligand (eg, antibody or fragment) comprises (a) a variable domain that is encoded by a human V region nucleotide sequence, wherein the V nucleotide sequence is derived from recombination of human VH, D and JH gene segments or human VL and JL gene segments; or (b) a constant region domain encoded by a C region gene segment; Wherein a first gene segment of said gene segments of (a), or said C region gene segment of (b) comprises a first single nucleotide polymorphism (SNP) encoding a first amino acid polymorphism; and (ii) the genome of said human comprises said first SNP or wherein said human expresses (a′) an antibody variable domain comprising said first amino acid polymorphism or (b′) an antibody constant domain comprising said first amino acid polymorphism.","A Sixteenth Configuration provides the ligand, method, use, kit or composition of the invention, wherein the ligand comprises or consists of an antibody or fragment that comprises a human antibody variable domain derived from the recombination of a human V gene segment and a human J gene segment (and optionally a human D gene segment when the variable domains are VH domains); and wherein the genome of the human comprises said human V gene segment and/or the human expresses antibodies comprising antibody variable domains derived from the recombination of said human V gene segment and a human J gene segment (and optionally a human D gene segment).","A Sixteenth Configuration provides the ligand, method, use, kit or composition of the invention, wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused human PCSK9 receptor) comprises a human heavy chain constant domain encoded by a first constant region nucleotide sequence; and wherein the genome of the human comprises a heavy chain constant region nucleotide sequence that is identical to said first constant region nucleotide sequence and/or the human expresses antibodies comprising said human constant domain.","A Seventeenth Configuration provides the ligand, method, use, kit or composition of the invention, wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused TOI receptor) comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 or a Leu corresponding to position 206 of SEQ ID NO: 42 and wherein the genome of the human comprises a gamma-1 heavy chain constant region nucleotide sequence that encodes such an Asp or Leu or the human expresses antibodies comprising human gamma-1 constant regions comprising such an Asp or Leu.","A Eighteenth Configuration provides the ligand, method, use, kit or composition of the invention, wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused TOI receptor) comprises a human gamma-2 heavy chain constant region that comprises an amino acid selected from the group consisting of a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44, a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44; and wherein the genome of the human comprises a gamma-2 heavy chain constant region nucleotide sequence that encodes such a selected amino acid or the human expresses antibodies comprising human gamma-2 constant regions comprising such a selected amino acid.","A Nineteenth Configuration provides the ligand, method, use, kit or composition of the invention, wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused TOI receptor) comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 or a Cys corresponding to position 87 of SEQ ID NO: 50; and wherein the genome of the human comprises a kappa light chain constant region nucleotide sequence that encodes such a Val or Cys or the human expresses antibodies comprising human kappa light chain constant regions comprising such a Val or Cys.","A Twentieth Configuration provides the ligand, method, use, kit or composition of the invention, wherein the ligand comprises or consists of an antibody or fragment, wherein the antibody or fragment comprises a VH domain that is derived from the recombination of a human VH gene segment, a human D gene segment and a human JH gene segment, wherein the VH gene segment is selected from the group consisting of (i) IGHV1-18*01 and the genome of the human comprises a human IGHV1-18*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGHV1-18*01; or (ii) IGVH1-46*01 and the genome of the human comprises a human IGHV1-46*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGHV1-46*01.A Twenty-First Configuration provides the ligand, method, use, kit or composition of the invention, wherein the ligand comprises or consists of an antibody or fragment, wherein the antibody or fragment comprises a VL domain that is derived from the recombination of a human VL gene segment and a human JL gene segment, wherein the VL gene segment is selected from the group consisting of (i) IGKV4-1*01 and the genome of the human comprises a human IGKV4-1*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGKV4-1*01; (ii) IGLV2-14*01 and the genome of the human comprises a human IGLV2-14*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGLV2-14*01; or (iii) IGKV1-13*02 and the genome of the human comprises a human IGKV1-13*02 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGKV1-13*02."],["CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of co-pending U.S. application Ser.","No.","14/331,730 filed Jul.","15, 2014, the entire content of which is incorporated by reference.","SEQUENCE LISTING The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety.","Said ASCII copy, created on Jul.","14, 2014, is named 069496-080095_SL.txt and is 222,931 bytes in size.","TECHNICAL FIELD The technology described herein relates to ligands, e.g., antibodies for the treatment of disease.","BACKGROUND It is recognized that individual humans differ in their sequence and recently several individuals have had their genomes sequenced, for instance James Watson and Craig Venter.","Comparison of the genome sequence of individuals has revealed differences in their sequences in both coding and non-coding parts of the genome.","Some of these variations in humans are significant and contribute to phenotypic differences between individuals.","In extreme cases these will result in genetic disease.","The 1000 Genomes Project has the objective of cataloguing sequences in the human genome, involving sequencing the genomes of a very large sampling of individuals from diverse art-recognized human ethnic populations.","SUMMARY Through the application of human genetic variation analysis and rationally-designed sequence selection the present invention provides for improved human patient diagnosis and therapy.","Importantly, the invention enables tailored medicines that address individual human patient genotypes or phenotypes.","The inventor's analysis of large numbers of naturally-occurring genomic human TOI sequences reveals that there is significant variation across diverse human populations and provides for the ability for correlation between individual human patients and tailored medical and diagnostic approaches addressing the target.","The technical applications of these findings, as per the present invention, thus contribute to better treatment, prophylaxis and diagnosis in humans and provides for patient benefit by enabling personalized medicines and therapies.","This provides advantages of better prescribing, less wastage of medications and improved chances of drug efficacy and better diagnosis in patients.","Furthermore, the inventor surprisingly realised that some rarer natural forms, although present in humans at much lower frequencies than the common form, nevertheless are represented in multiple and ethnically-diverse human populations and usually with many human examples per represented ethnic population.","Thus, the inventor realised that targeting such rarer forms would provide for effective treatment, prophylaxis or diagnosis across many human ethnic populations, thereby extending the utility of the present invention and better serving patients in those populations.","With this, the inventor realised that there is significant industrial and medical application for the invention in terms of guiding the choice of an anti-TOI ligand for administration to human patients for therapy and/or prophylaxis of TOI-mediated or associated diseases and conditions.","In this way, the patient receives drugs and ligands that are tailored to their needs—as determined by the patient's genetic or phenotypic makeup.","Hand-in-hand with this, the invention provides for the genotyping and/or phenotyping of patients in connection with such treatment, thereby allowing a proper match of drug to patient.","This increases the chances of medical efficacy, reduces the likelihood of inferior treatment using drugs or ligands that are not matched to the patient (eg, poor efficacy and/or side-effects) and avoids pharmaceutical mis-prescription and waste.","To this end, the invention provides:— In a First Configuration A method of treating or preventing a disease or condition in a human, wherein the disease or condition is mediated by a Target of Interest (TOI), wherein the TOI is present in humans as different polymorphic variants, the method comprising a.","Administering to the human an anti-TOI ligand to target a TOI variant in the human and treat or prevent said disease or condition, wherein the TOI in said human is encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or wherein the TOI in said human is encoded by a nucleotide sequence having a total human genotype frequency of less than 50%; wherein b.","Before step (a) said human has been or is genotyped as positive for said nucleotide sequence or phenotyped as positive for said TOI variant.","In a Second Configuration A method of treating or preventing a disease or condition in a human, wherein the disease or condition is mediated by a Target of Interest (TOI), wherein the TOI is present in humans as different polymorphic variants, the method comprising a.","Administering to the human an anti-TOI ligand to target a TOI variant in the human and treat or prevent said disease or condition, wherein the TOI in said human is encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or wherein the TOI in said human is encoded by a nucleotide sequence having a total human genotype frequency of less than 50%; wherein b. before step (a) the ligand has been or is determined as capable of binding to said TOI variant.","In a Third Configuration A method of treating or preventing a disease or condition in a human, wherein the disease or condition is mediated by a Target of Interest (TOI), wherein the TOI is present in humans as different polymorphic variants, the method comprising a.","Administering to the human an anti-TOI ligand to target a TOI variant in the human and treat or prevent said disease or condition, wherein the TOI in said human is a variant encoded by a nucleotide sequence having a cumulative human allele frequency of more than 50% and/or having a total human genotype frequency of more than 50%; wherein b.","Before step (a) said human has been or is genotyped as negative for a variant nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%; or phenotyped as negative for a TOI variant encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.","In a Fourth Configuration An anti-human TOI ligand for use in a method of treating and/or preventing a TOI-mediated disease or condition in a human, wherein the TOI is present in humans as different polymorphic variants and wherein the genome of said human comprises a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, the method comprising administering the ligand to the human.","In a Fifth Configuration A ligand that binds a human TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, for use in a method comprising the step of using the ligand to target said TOI in a human to treat and/or prevent a disease or condition mediated by TOI, the method comprising administering the ligand to the human.","In a Sixth Configuration A pharmaceutical composition or kit for treating or preventing a condition or disease mediated by a TOI.","In a Seventh Configuration A method of producing an anti-human TOI antibody binding site, the method comprising obtaining a plurality of anti-TOI antibody binding sites, screening the antibody binding sites for binding to a TOI comprising an amino acid sequence encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, or to a peptide thereof that comprises an amino acid variation from the corresponding sequence encoded by the TOI-encoding nucleotide sequence having the highest cumulative human allele frequency and/or the highest total human genotype frequency, and isolating an antibody binding site that binds in the screening step.","In a Eighth Configuration A method of producing an anti-human TOI antibody, the method comprising immunising a non-human vertebrate (eg, a mouse or a rat) with a TOI comprising an amino acid sequence encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, or to a peptide thereof that comprises an amino acid variation from the corresponding sequence encoded by the TOI-encoding nucleotide sequence having the highest cumulative human allele frequency and/or the highest total human genotype frequency, and isolating an antibody that binds a TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, and optionally producing a TOI-binding fragment or derivative of the isolated antibody.","In a Ninth Configuration A kit for TOI genotyping a human, wherein the kit comprises a nucleic acid comprising a nucleotide sequence that specifically hybridises to a TOI nucleotide sequence selected having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50% or an RNA transcript thereof; and/or the nucleic acid comprises a nucleotide sequence that comprises at least 10 contiguous nucleotides of a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50% or is an antisense sequence thereof.","In a Tenth Configuration Use of an anti-TOI ligand that binds a human TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, in the manufacture of a medicament for treating and/or preventing a TOI-mediated disease or condition in a human whose genome comprises a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.","In a Eleventh Configuration Use of an anti-TOI ligand that binds a human TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, in the manufacture of a medicament for targeting said TOI in a human to treat and/or prevent a disease or condition mediated by TOI.","In a Twelfth Configuration A method of targeting a TOI for treating and/or preventing a TOI-mediated disease or condition in a human, the method comprising administering an anti-TOI ligand to a human comprising a TOI nucleotide sequence selected having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, whereby a TOI encoded by said nucleotide sequence is targeted.","In a Thirteenth Configuration A method of TOI genotyping a nucleic acid sample of a human, the method comprising identifying in the sample the presence of a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.","In a Fourteenth Configuration A method of TOI typing a protein sample of a human, the method comprising identifying in the sample the presence of a TOI amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.","In an example, the TOI is a human TOI selected from the group consisting of PCSK9, VEGF-A and IL6 receptor.","A Fifteenth Configuration provides a ligand, method, use, kit or composition of the invention, wherein (i) the ligand (eg, antibody or fragment) comprises (a) a variable domain that is encoded by a human V region nucleotide sequence, wherein the V nucleotide sequence is derived from recombination of human VH, D and JH gene segments or human VL and JL gene segments; or (b) a constant region domain encoded by a C region gene segment; Wherein a first gene segment of said gene segments of (a), or said C region gene segment of (b) comprises a first single nucleotide polymorphism (SNP) encoding a first amino acid polymorphism; and (ii) the genome of said human comprises said first SNP or wherein said human expresses (a′) an antibody variable domain comprising said first amino acid polymorphism or (b′) an antibody constant domain comprising said first amino acid polymorphism.","A Sixteenth Configuration provides the ligand, method, use, kit or composition of the invention, wherein the ligand comprises or consists of an antibody or fragment that comprises a human antibody variable domain derived from the recombination of a human V gene segment and a human J gene segment (and optionally a human D gene segment when the variable domains are VH domains); and wherein the genome of the human comprises said human V gene segment and/or the human expresses antibodies comprising antibody variable domains derived from the recombination of said human V gene segment and a human J gene segment (and optionally a human D gene segment).","A Sixteenth Configuration provides the ligand, method, use, kit or composition of the invention, wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused human PCSK9 receptor) comprises a human heavy chain constant domain encoded by a first constant region nucleotide sequence; and wherein the genome of the human comprises a heavy chain constant region nucleotide sequence that is identical to said first constant region nucleotide sequence and/or the human expresses antibodies comprising said human constant domain.","A Seventeenth Configuration provides the ligand, method, use, kit or composition of the invention, wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused TOI receptor) comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 or a Leu corresponding to position 206 of SEQ ID NO: 42 and wherein the genome of the human comprises a gamma-1 heavy chain constant region nucleotide sequence that encodes such an Asp or Leu or the human expresses antibodies comprising human gamma-1 constant regions comprising such an Asp or Leu.","A Eighteenth Configuration provides the ligand, method, use, kit or composition of the invention, wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused TOI receptor) comprises a human gamma-2 heavy chain constant region that comprises an amino acid selected from the group consisting of a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44, a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44; and wherein the genome of the human comprises a gamma-2 heavy chain constant region nucleotide sequence that encodes such a selected amino acid or the human expresses antibodies comprising human gamma-2 constant regions comprising such a selected amino acid.","A Nineteenth Configuration provides the ligand, method, use, kit or composition of the invention, wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused TOI receptor) comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 or a Cys corresponding to position 87 of SEQ ID NO: 50; and wherein the genome of the human comprises a kappa light chain constant region nucleotide sequence that encodes such a Val or Cys or the human expresses antibodies comprising human kappa light chain constant regions comprising such a Val or Cys.","A Twentieth Configuration provides the ligand, method, use, kit or composition of the invention, wherein the ligand comprises or consists of an antibody or fragment, wherein the antibody or fragment comprises a VH domain that is derived from the recombination of a human VH gene segment, a human D gene segment and a human JH gene segment, wherein the VH gene segment is selected from the group consisting of (i) IGHV1-18*01 and the genome of the human comprises a human IGHV1-18*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGHV1-18*01; or (ii) IGVH1-46*01 and the genome of the human comprises a human IGHV1-46*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGHV1-46*01.A Twenty-First Configuration provides the ligand, method, use, kit or composition of the invention, wherein the ligand comprises or consists of an antibody or fragment, wherein the antibody or fragment comprises a VL domain that is derived from the recombination of a human VL gene segment and a human JL gene segment, wherein the VL gene segment is selected from the group consisting of (i) IGKV4-1*01 and the genome of the human comprises a human IGKV4-1*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGKV4-1*01; (ii) IGLV2-14*01 and the genome of the human comprises a human IGLV2-14*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGLV2-14*01; or (iii) IGKV1-13*02 and the genome of the human comprises a human IGKV1-13*02 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGKV1-13*02.BRIEF DESCRIPTION OF THE DRAWINGS This patent or application file contains at least one drawing executed in color.","Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.","FIG.","1 shows in silico modeling of PCSK9 surface variant residues.","FIG.","2 depicts the cumulative allele frequency distribution across the 1000 Genomes Project database of human VH3-23 alleles comprising SNP rs56069819 (such alleles denoted “C” and the most frequent allele (which does not comprise this SNP) denoted “A”).","The figure shows that VH3-23 alleles comprising SNP rs56069819 are present at a cumulative frequency of 11% across all human ethnic populations taken as a whole, whereas in certain specific human ethnic sub-populations (ASW, LWK, YRI, CEU and GBR) such alleles are present at an above-average cumulative frequency.","Indicated in the figure are those human PCSK9 variant forms (marked “Variants”) that are found in the various sub-populations with above-average occurrence of human VH3-23 alleles comprising SNP rs56069819.FIG.","3 depicts frameworks and CDRs encoded by VH3-23*04 as obtained from the IMGT database (available on the World Wide Web at www.IMGT.org).","FIG.","3 discloses the nucleotide sequences as SEQ ID NOS 68, 68, 68, 70, 70, 70, 71, 73, 75, 39 and 76, respectively, in order of appearance.","FIG.","3 discloses the coded amino acid sequences as SEQ ID NOS 69, 69, 69, 69, 69, 69, 72, 74, 74, 38 and 77, respectively, in order of appearance.","FIG.","4 depicts sequences of VH3-23*04.The portion of VH3-23*04 comprising the FW1 residue change of rs56069819 (SEQ ID NO: 38).","The portion of the nucleic acid sequence encoding rs56069819 is depicted (SEQ ID NO: 39).","The FW1 encoded by VH3-23*04 is depicted (SEQ ID NO: 40).","DETAILED DESCRIPTION The skilled person will know that SNPs or other changes that translate into amino acid variation can cause variability in conformation or activity of human targets to be addressed.","This has spawned great interest in personalized medicine where genotyping and knowledge of protein and nucleotide variability is used to tailor medicines and diagnosis of patients more effectively.","The present invention provides for tailored pharmaceuticals and testing that specifically addresses rarer variant forms of a human target of interest (TOI).","The present invention harnesses the power of human genetic variation analysis and rationally-designed sequence selection.","The technical applications of these approaches, as per the present invention, contribute to better treatment, prophylaxis and diagnosis in humans and provides for patient benefit by providing choice and enabling personalized medicines and therapies.","This provides advantages of better prescribing, less wastage of medications and improved chances of drug efficacy and better diagnosis in patients.","As sources of genomic sequence variation data, the skilled person will be aware of the available databases and resources (including updates thereof) provided by the following:— 1.HapMap (The International HapMap Consortium.","2003; available on the World Wide Web at hapmap.ncbi.nlm.nih.gov/index.html.en).","The HapMap Project is an international project that aims to compare the genetic sequences of different individuals to identify chromosomal regions containing shared genetic variants.","The HapMap www site provides tools to identify chromosomal regions and the variant therein, with options to drill down to population level frequency data.","2.1000 Genomes Project (The 1000 Genomes Project Consortium 2010; available on the World Wide Web at 1000genomes.org/).","This resource provides complete genomic sequence for at least 2500 unidentified individuals from one of 25 distinct population groups.","3.Japanese SNP Database (H. Haga et al.","2002; available on the World Wide Web at snp.ims.u-tokyo.ac.jp/index.html).","Based on a study identifying 190,562 human genetic variants.","The present invention involves the identification and cataloguing of naturally-occurring human genomic target sequence variants, including those found to be relatively low-frequency or rare variants that segregate with specific human ethnic populations and in many individual humans.","An aspect of the invention is based on rational design of sequence selection addressing the desirability to tailor medicaments and diagnostics to rarer, but yet still significant groups of human individuals that suffer from, or have the potential to suffer from (ie, who are at risk of), a disease or condition mediated or associated with the target of interest.","In devising this rational design of the present aspect of the invention, the inventor included considerations of the spread of prevalence of naturally-occurring target variant sequences across multiple, diverse human ethnic populations, as well as the importance of addressing such populations where many individuals are likely to display a genotype and/or phenotype of one or more of the variants being analysed.","As part of this design, the inventor saw the importance of adopting the art-recognised classifications of human ethnic populations, and in this respect the inventor based the analysis and design on the recognised human ethnic populations adopted by the 1000 Genomes Project, since this is a resource that is, and will continue to be, widely adopted by the scientific and medical community.","Thus, in this aspect of the invention, the inventor designed the following variant sequence selection criteria, these being criteria that the inventor realised would provide for useful medical drugs and diagnostics to tailored need in the human population.","Selection Criteria Three or four of the following:— Naturally-occurring human target variant sequences having a cumulative human allele frequency of 35% or less; Naturally-occurring human target variant sequences having a total human genotype frequency of 40% or less; Naturally-occurring human target variant sequences found in many different human ethnic populations (using the standard categorisation of the 1000 Genomes Project; see Table 4 below); and Naturally-occurring human target variant sequences found in many individuals distributed across such many different ethnic populations.","The inventor's selection included, as a consideration, selection for nucleotide variation that produced amino acid variation in corresponding TOI forms (ie, non-synonymous variations), as opposed to silent variations that do not alter amino acid residues in the target protein.","In an embodiment, the cumulative human allele frequency is 30, 25, 20, 15, 10 or 5% or less, eg, in the range from 1 to 20% or 1 to 15% or 1 to 10%.","In an embodiment, the total human genotype frequency is 35, 30, 25, 20, 15, 10 or 5% or less, eg, in the range from 1 to 25%, 1 to 20%, 1 to 15%, 1 to about 15%, 1 to 10%, 1 to about 10% or 1 to 5% or 1 to about 5%.","In an embodiment, the naturally-occurring human target variant sequences are found in at least 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 different human ethnic populations (using the standard categorisation of the 1000 Genomes Project).","In an embodiment, the naturally-occurring human target variant sequences are found in at least 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 130, 140 or 150 individuals distributed across such many different ethnic populations.","In an example, the following criteria are applied:— Naturally-occurring human target variant sequences having a cumulative human allele frequency of 15% or less; Naturally-occurring human target variant sequences having a total human genotype frequency of 20% or less; Naturally-occurring human target variant sequences found in at least 5 different human ethnic populations (using the standard categorisation of the 1000 Genomes Project); and Naturally-occurring human target variant sequences found in many individuals distributed across such many different ethnic populations.","In an example, the criteria are applied with reference to one or more human genomic sequence databases as described herein.","For example, the criteria are those as applied to the 1000 Genomes database.","For example in any aspect example, embodiment or configuration of the invention, the 1000 Genomes database release 13.For example, the 1000 Genomes database in its most recent version as at 1 Oct. 2013.Optionally, further sequence analysis and 3D in silico modelling (eg, see FIG.","1) can also be used as an additional selection criterion: variants whose variant amino acid residues (versus the most common form of human TOI) are surface-exposed on the target are desirable for selection, since the inventor saw these as contributing to determining the topography of the target and potentially contributing to how and where ligand binding on the target occurs.","The following bioinformatics protocol is envisaged to identify human sequences for use in the present invention: (a) Identify a genomic region containing a target sequence of interest (‘target genomic region’) and calculate the genomic coordinates, using coordinates that match the sequence assembly build used by either the 1000 Genomes Project or International HapMap project (or another selected human gene database of choice).","(b) Identify genomic variants mapped to the genomic region previously identified in (a).","Retrieve allele frequencies for variants for each super population and preferably sub-population where such data is available.","The VWC tools for the 1000 Genomes Project can be used for this step.","(c) Filter list of genomic variants from target genomic region to contain only variants classed as either ‘non-synonymous’ single nucleotide polymorphisms (SNPs) or genomic ‘insertions or deletions’ (indels).","Filter further to include those that are present in exonic sequences only.","“Non-synonymous” refers to nucleotide variation that produces amino acid variation (ie, excluding silent mutations).","(d) Correlate population frequency data for each of the identified variants for each of the super populations (for example ‘European Ancestry’, ‘East Asian ancestry’, ‘West African ancestry’, ‘Americas’, and ‘South Asian ancestry’) to identify those variants that segregate with less than two super-populations.","Further correlate all identified variants with each of the sub-populations (for example, ‘European ancestry’ super-population might be subdivided into groups such as ‘CEU—Utah residents with Northern or Western European ancestry’, ‘TSI Toscani in Italia’ and ‘British from England and Scotland’) and produce a second score for rarity of variants within a super-population.","(e) Collect one or more sequences that show segregation to specific sub-populations for use in the present invention, eg, according to selection criteria as described herein.","Human Populations Optionally the ethnic populations are selected from those identified in the 1000 Genomes Project database.","In this respect, see Table 4 which provides details of the ethnic populations on which the 1000 Genomes Project database is based.","N A Rosenberg et al (Science 20 Dec. 2002: vol.","298 no.","5602 2342-2343) studied the genetic structure of human populations of differing geographical ancestry.","In total, 52 populations were sampled, these being populations with: African ancestry (Mbuti Pygmies, Biaka Pygmies, San peoples, and speakers of Niger-Kordofanian languages (Bantu, Yoruba or Mandenka populations), Eurasian ancestry (European ancestry (Orcadian, Adygel, Basque, French, Russians, Italians, Sardinian, Tuscan), Middle Eastern ancestry (Mozabite, Bedouin, Druze, Palestinians), Central/South Asian ancestry (Balochl, Brahul, Makrani, Sindhi, Pathan, Burusho, Hazara, Uygur, Kalash)), East Asian ancestry (Han, Dal, Daur, Hezhen, Lahu, Miao, Oroqen, She, Tujia, Tu, Xibo, Yi, Mongola, Naxi, Cambodian, Japanese, Yakut), Oceanic ancestry (Melanesian, Papuan); or Americas ancestry (Karitiana, Surui, Colombian, Maya, Pima).","The International HapMap Project, Nature, 2003 Dec. 18; 426(6968):789-96, discloses that goal of the HapMap Project: to determine the common patterns of DNA sequence variation in the human genome by determining the genotypes of one million or more sequence variants, their frequencies and the degree of association between them in DNA samples from populations with ancestry from parts of Africa, Asia and Europe.","The relevant human populations of differing geographical ancestry include Yoruba, Japanese, Chinese, Northern European and Western European populations.","More specifically:— Utah population with Northern or Western European ancestry (samples collected in 1980 by the Centre d'Etude du Polymorphisme Humain (CEPH)); population with ancestry of Yoruba people from Ibadan, Nigeria; population with Japanese ancestry; and population with ancestry of Han Chinese from China.","The authors, citing earlier publications, suggest that ancestral geography is a reasonable basis for sampling human populations.","A suitable sample of human populations used in the present invention is as follows:— (a) European ancestry (b) Northern European ancestry; Western European ancestry; Toscani ancestry; British ancestry, Finnish ancestry or Iberian ancestry.","(c) More specifically, population of Utah residents with Northern and/or Western European ancestry; Toscani population in Italia; British population in England and/or Scotland; Finnish population in Finland; or Iberian population in Spain.","(a) East Asian ancestry (b) Japanese ancestry; Chinese ancestry or Vietnamese ancestry.","(c) More specifically, Japanese population in Tokyo, Japan; Han Chinese population in Beijing, China; Chinese Dai population in Xishuangbanna; Kinh population in Ho Chi Minh City, Vietnam; or Chinese population in Denver, Colo., USA.","(a) West African ancestry (b) Yoruba ancestry; Luhya ancestry; Gambian ancestry; or Malawian ancestry.","(c) More specifically, Yoruba population in Ibadan, Nigeria; Luhya population in Webuye, Kenya; Gambian population in Western Division, The Gambia; or Malawian population in Blantyre, Malawi.","(a) Population of The Americas (b) Native American ancestry; Afro-Caribbean ancestry; Mexican ancestry; Puerto Rican ancestry; Columbian ancestry; or Peruvian ancestry.","(c) More specifically, population of African Ancestry in Southwest US; population of African American in Jackson, Miss.","; population of African Caribbean in Barbados; population of Mexican Ancestry in Los Angeles, Calif.; population of Puerto Rican in Puerto Rico; population of Colombian in Medellin, Colombia; or population of Peruvian in Lima, Peru.","(a) South Asian ancestry (b) Ahom ancestry; Kayadtha ancestry; Reddy ancestry; Maratha; or Punjabi ancestry.","(c) More specifically, Ahom population in the State of Assam, India; Kayadtha population in Calcutta, India; Reddy population in Hyderabad, India; Maratha population in Bombay, India; or Punjabi population in Lahore, Pakistan.","In any configuration of the invention, in one embodiment, each human population is selected from a population marked “(a)” above.","In any configuration of the invention, in another embodiment, each human population is selected from a population marked “(b)” above.","In any configuration of the invention, in another embodiment, each human population is selected from a population marked “(c)” above.","In one embodiment the ethnic populations are selected from the group consisting of an ethnic population with European ancestry, an ethnic population with East Asian, an ethnic population with West African ancestry, an ethnic population with Americas ancestry and an ethnic population with South Asian ancestry.","In one embodiment the ethnic populations are selected from the group consisting of an ethnic population with Northern European ancestry; or an ethnic population with Western European ancestry; or an ethnic population with Toscani ancestry; or an ethnic population with British ancestry; or an ethnic population with Icelandic ancestry; or an ethnic population with Finnish ancestry; or an ethnic population with Iberian ancestry; or an ethnic population with Japanese ancestry; or an ethnic population with Chinese ancestry; or an ethnic population Vietnamese ancestry; or an ethnic population with Yoruba ancestry; or an ethnic population with Luhya ancestry; or an ethnic population with Gambian ancestry; or an ethnic population with Malawian ancestry; or an ethnic population with Native American ancestry; or an ethnic population with Afro-Caribbean ancestry; or an ethnic population with Mexican ancestry; or an ethnic population with Puerto Rican ancestry; or an ethnic population with Columbian ancestry; or an ethnic population with Peruvian ancestry; or an ethnic population with Ahom ancestry; or an ethnic population with Kayadtha ancestry; or an ethnic population with Reddy ancestry; or an ethnic population with Maratha; or an ethnic population with Punjabi ancestry.","Anti-Target Ligands The invention provides useful anti-target ligands for addressing humans suffering from or likely to suffer from a disease or condition mediated or associated with the TOI.","For example, the ligand specifically binds to the TOI variant as per the invention.","The ligand may inhibit or antagonise the activity of the target, eg, the ligand neutralises the target.","The skilled person will be familiar with neutralising ligands in general, such as antibodies or antibody fragments, and can readily test suitable ligands for specific binding and/or neutralisation of a target in vitro or in an in vivo assay.","An antibody “fragment” comprises a portion of an intact antibody, preferably the antigen binding and/or the variable region of the intact antibody.","Examples of antibody fragments include dAb, Fab, Fab′, F(ab′)2 and Fv fragments; diabodies; linear antibodies; single-chain antibody molecules and multispecific antibodies formed from antibody fragments.","In an embodiment, the ligand of the invention is or comprises an antibody or antibody fragment, for example an antibody or fragment comprising human variable regions (and optionally also human constant regions).","Anti-TOI or TOI-binding or targeting antibodies and fragments can be prepared according to any known method, eg, using transgenic mice (eg, the Kymouse™ or Velocimouse™, or Omnimouse™, Xenomouse™, HuMab Mouse™ or MeMo Mouser™), rats (eg, the Omnirat™), camelids, sharks, rabbits, chickens or other non-human animals immunised with the TOI followed optionally by humanisation of the constant regions and/or variable regions to produce human or humanised antibodies.","In an example, display technologies can be used, such as yeast, phage or ribosome display, as will be apparent to the skilled person.","Standard affinity maturation, eg, using a display technology, can be performed in a further step after isolation of an antibody lead from a transgenic animal, phage display library or other library.","Representative examples of suitable technologies are described in US20120093818 (Amgen, Inc), which is incorporated herein by reference, eg, the methods set out in paragraphs [0309] to [0346].","Although this is with reference to PCSK9, the antibody-generating methods can be applied to other TOIs as per the broadest scopes of the present invention.","Generally, a VELOCIMMUNE™ or other mouse or rat can be challenged with the antigen of interest, and lymphatic cells (such as B-cells) are recovered from the mice that express antibodies.","The lymphatic cells may be fused with a myeloma cell line to prepare immortal hybridoma cell lines, and such hybridoma cell lines are screened and selected to identify hybridoma cell lines that produce antibodies specific to the antigen of interest.","DNA encoding the variable regions of the heavy chain and light chain may be isolated and linked to desirable isotypic constant regions of the heavy chain and light chain.","Such an antibody protein may be produced in a cell, such as a CHO cell.","Alternatively, DNA encoding the antigen-specific chimaeric antibodies or the variable domains of the light and heavy chains may be isolated directly from antigen-specific lymphocytes.","Initially, high affinity chimaeric antibodies are isolated having a human variable region and a mouse constant region.","As described below, the antibodies are characterized and selected for desirable characteristics, including affinity, selectivity, epitope, etc.","The mouse constant regions are replaced with a desired human constant region to generate the fully human antibody of the invention, for example wild-type or modified IgG1 or IgG4 (for example, SEQ ID NO: 751, 752, 753 in US2011/0065902, which sequences are incorporated herein by reference for use in the ligands of the present invention).","While the constant region selected may vary according to specific use, high affinity antigen-binding and target specificity characteristics reside in the variable region.","In an example, the ligand of the invention is or comprises a nucleic acid, eg, RNA, eg, siRNA that hybridises under stringent condition to the TOI variant sequence, eg, hybridises a nucleotide sequence comprising one or more nucleotides that are variant (versus the most common TOI sequence, eg, with reference to the 1000 Genomes Project database).","Target binding ability, specificity and affinity (Kd, Koff and/or Kon) can be determined by any routine method in the art, eg, by surface plasmon resonance (SPR).","The term “Kd”, as used herein, is intended to refer to the equilibrium dissociation constant of a particular antibody-antigen interaction.","In one embodiment, the surface plasmon resonance (SPR) is carried out at 25° C. In another embodiment, the SPR is carried out at 37° C. In one embodiment, the SPR is carried out at physiological pH, such as about pH7 or at pH7.6 (eg, using Hepes buffered saline at pH7.6 (also referred to as HBS-EP)).","In one embodiment, the SPR is carried out at a physiological salt level, eg, 150 mM NaCl.","In one embodiment, the SPR is carried out at a detergent level of no greater than 0.05% by volume, eg, in the presence of P20 (polysorbate 20; eg, Tween-20™) at 0.05% and EDTA at 3 mM.","In one example, the SPR is carried out at 25° C. or 37° C. in a buffer at pH7.6, 150 mM NaCl, 0.05% detergent (eg, P20) and 3 mM EDTA.","The buffer can contain 10 mM Hepes.","In one example, the SPR is carried out at 25° C. or 37° C. in HBS-EP.","HBS-EP is available from Teknova Inc (California; catalogue number H8022).","In an example, the affinity of the ligand (eg, antibody) is determined using SPR by 1.Coupling anti-mouse (or other relevant human, rat or non-human vertebrate antibody constant region species-matched) IgG (eg, Biacore™ BR-1008-38) to a biosensor chip (eg, GLM chip) such as by primary amine coupling; 2.Exposing the anti-mouse IgG (or other matched species antibody) to a test IgG antibody to capture test antibody on the chip; 3.Passing the test antigen over the chip's capture surface at 1024 nM, 256 nM, 64 nM, 16 nM, 4 nM with a 0 nM (i.e.","buffer alone); and 4.And determining the affinity of binding of test antibody to test antigen using surface plasmon resonance, eg, under an SPR condition discussed above (eg, at 25° C. in physiological buffer).","SPR can be carried out using any standard SPR apparatus, such as by Biacore™ or using the ProteOn XPR36™ (Bio-Rad®).","Regeneration of the capture surface can be carried out with 10 mM glycine at pH1.7.This removes the captured antibody and allows the surface to be used for another interaction.","The binding data can be fitted to 1:1 model inherent using standard techniques, eg, using a model inherent to the ProteOn XPR36™ analysis software.","In an example, the ligand of the invention is contained in a medical container, eg, a vial, syringe, IV container or an injection device (eg, an intraocular or intravitreal injection device).","In an example, the ligand is in vitro, eg, in a sterile container.","In an example, the invention provides a kit comprising the ligand of the invention, packaging and instructions for use in treating or preventing or diagnosing in a human a disease or condition mediated by the TOI.","In an example, the instructions indicate that the human should be genotyped for a TOI variant sequence of the invention before administering the ligand to the human.","In an example, the instructions indicate that the human should be phenotyped for a TOI variant of the invention before administering the ligand to the human.","In an example, the human is of Chinese (eg, Han) ethnicity and the instructions are in Chinese (eg, Mandarin).","In an example, the instructions comprise directions to administer alirocumab or evolocumab to said human.","The invention relates to the concepts set out in the following clauses.","Clause 1 A method of treating or preventing a disease or condition in a human, wherein the disease or condition is mediated by a Target of Interest (TOI), wherein the TOI is present in humans as different polymorphic variants, the method comprising a.","Administering to the human an anti-TOI ligand to target a TOI variant in the human and treat or prevent (eg, by at least 40, 50, 60, 70, 80, 90 or 95%) said disease or condition, wherein the TOI in said human is encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or wherein the TOI in said human is encoded by a nucleotide sequence having a total human genotype frequency of less than 50%; wherein Before step (a) said human has been or is genotyped as positive for said nucleotide sequence or phenotyped as positive for said TOI variant, or the method comprises before step (a) genotyping the human as positive for said nucleotide sequence or phenotyping the human as positive for said TOI variant.","In any aspect, configuration, example, embodiment, clause or concept herein, frequencies may be determined using bioinformatics.","In any aspect, configuration, example, embodiment, clause or concept herein, frequencies may be determined by reference to a database comprising at least 1000 or 2000 human sequences.","In any aspect, configuration, example, embodiment, clause or concept herein “heterozygous human genotype frequency” means the cumulative frequency of all genotypes in the sample or database or in humans having one occurrence of the rare variant allele and one occurrence of another allele (heterozygous state), eg, genotype in 1000 Genomes database.","In any aspect, configuration, example, embodiment, clause or concept herein “homozygous human genotype frequency means the cumulative frequency of two occurrences of the variant allele (homozygous state), eg, genotype in 1000 Genomes Project database.","In any aspect, configuration, example, embodiment, clause or concept herein “total human genotype frequency” means the total of heterozygous plus homozygous human genotype frequencies.","In any aspect, configuration, example, embodiment, clause or concept herein “cumulative human allele frequency” refers to the total of all occurrences of the variant allele in the sample or database or in humans, eg, in the 1000 Genomes Project database.","Clause 2: The method of clause 1, wherein before step (a) the ligand has been or is determined as being capable of binding to said TOI variant, eg, with an affinity (Kd) disclosed below.","In an example, the ligand is (or has been determined as) a neutraliser of the TOI.","In an example, determination is carried out in a human (eg, in a clinical trial).","In an example, determination is carried out in a non-human, eg, in a mouse, rat, rabbit, pig, dog, sheep or non-human primate (eg, Cynomolgous monkey, rhesus monkey or baboon).","Clause 3: A method of treating or preventing a disease or condition in a human, wherein the disease or condition is mediated by a Target of Interest (TOI), wherein the TOI is present in humans as different polymorphic variants, the method comprising a.","Administering to the human an anti-TOI ligand to target a TOI variant in the human and treat or prevent (eg, by at least 40, 50, 60, 70, 80, 90 or 95%) said disease or condition, wherein the TOI in said human is encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or wherein the TOI in said human is encoded by a nucleotide sequence having a total human genotype frequency of less than 50%; wherein b.","Before step (a) the ligand has been or is determined as capable of binding to said TOI variant, eg, with an affinity (Kd) disclosed below.","In an example, the ligand is (or has been determined as) a neutraliser of the TOI.","In an example, determination is carried out in a human (eg, in a clinical trial).","In an example, determination is carried out in a non-human, eg, in a mouse, rat, rabbit, pig, dog, sheep or non-human primate (eg, Cynomolgous monkey, rhesus monkey or baboon).","Clause 4: The method of clause 3, wherein the genome of said human comprises a nucleotide sequence encoding said TOI variant; and before step (a) said nucleotide sequence has been or is determined as having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.","The TOI variant is not the most frequent.","Clause 5: The method of clause 3 or 4, wherein said human has been or is genotyped as positive for said variant nucleotide sequence before step (a), or the method comprises genotyping the human as positive for said variant nucleotide sequence before step (a).","Clause 6: The method of any preceding clause, wherein the human has been or is phenotyped as positive for said TOI variant before step (a), or the method comprises phenotyping the human as positive for said variant nucleotide sequence before step (a).","Clause 7: The method of any preceding clause, wherein said frequency is less than 10 or 15% (eg, from 1 to 10%).","In an embodiment, the cumulative human allele frequency is 30, 25, 20, 15, 10 or 5% or less, eg, in the range from 1 to 20% or 1 to 15% or 1 to 10%.","In an embodiment, the total human genotype frequency is 35, 30, 25, 20, 15, 10 or 5% or less, eg, in the range from 1 to 25%, 1 to 20%, 1 to 15%, 1 to about 15%, 1 to 10%, 1 to about 10% or 1 to 5% or 1 to about 5%.","Clause 8: The method of any preceding clause, wherein the ligand is capable of binding to two or more different TOI variants, each being encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% (eg, from 1 to 10%) and/or having a total human genotype frequency of less than 50% (eg, from 1 to 20%).","In an embodiment, the cumulative human allele frequency of each TOI variant is 30, 25, 20, 15, 10 or 5% or less, eg, in the range from 1 to 20% or 1 to 15% or 1 to 10%.","In an embodiment, the total human genotype frequency of each TOI variant is 35, 30, 25, 20, 15, 10 or 5% or less, eg, in the range from 1 to 25%, 1 to 20%, 1 to 15%, 1 to about 15%, 1 to 10%, 1 to about 10% or 1 to 5% or 1 to about 5%.","Clause 9: A method of treating or preventing a disease or condition in a human, wherein the disease or condition is mediated by a Target of Interest (TOI), wherein the TOI is present in humans as different polymorphic variants, the method comprising a.","Administering to the human an anti-TOI ligand to target a TOI variant in the human and treat or prevent (eg, by at least 40, 50, 60, 70, 80, 90 or 95%) said disease or condition, wherein the TOI in said human is a variant encoded by a nucleotide sequence having a cumulative human allele frequency of more than 50% (eg, the highest frequency) and/or having a total human genotype frequency of more than 50% (eg, the highest frequency); wherein b.","Before step (a) said human has been or is genotyped as negative for a variant nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%; or phenotyped as negative for a TOI variant encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%; or Before step (a) said the method comprises genotyping the human as negative for a variant nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%; or phenotyping the human as negative for a TOI variant encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.","In an embodiment, in (a) the cumulative human allele frequency is 55, 60, 65, 70, 75, 80, 85 or 90 or more but less than 95, 96, 97, 98, 99 or 100% (eg, in the range from 51 to 80%).","In an embodiment, in (a) the total human genotype frequency is 55, 60, 65, 70, 75, 80, 85 or 90 or more but less than 95, 96, 97, 98, 99 or 100% (eg, in the range from 51 to 80%).","In an embodiment, in (b) the cumulative human allele frequency is 30, 25, 20, 15, 10 or 5% or less, eg, in the range from 1 to 20% or 1 to 15% or 1 to 10%.","In an embodiment, in (b) the total human genotype frequency is 35, 30, 25, 20, 15, 10 or 5% or less, eg, in the range from 1 to 25%, 1 to 20%, 1 to 15%, 1 to about 15%, 1 to 10%, 1 to about 10% or 1 to 5% or 1 to about 5%.","Clause 10: The method of clause 9, wherein before step (a), the human has been or is phenotyped as positive for the most frequent TOI variant or genotyped for the nucleotide sequence thereof.","In an embodiment, before step (a) the human has been or is genotyped as positive for TOI variant nucleotide sequence having a cumulative human allele frequency of 55, 60, 65, 70, 75, 80, 85 or 90 or more but less than 95, 96, 97, 98, 99 or 100% (eg, in the range from 51 to 80%) or phenotyped for the TOI variant thereof.","In an embodiment, before step (a) the human has been or is genotyped as positive for TOI variant nucleotide sequence having a total human genotype frequency of 55, 60, 65, 70, 75, 80, 85 or 90 or more but less than 95, 96, 97, 98, 99 or 100% (eg, in the range from 51 to 80%) or phenotyped for the TOI variant thereof.","Clause 11: The method of clause 9 or 10, wherein before step (a) the ligand has been or is determined as being capable of binding to the most frequent TOI variant.","Clause 12: The method of clause 9, 10 or 11, wherein before step (a) the ligand has been or is determined as being substantially incapable of neutralising or inhibiting said TOI variant recited in step (b).","By “substantially incapable or neutralising or inhibiting” is meant: Neutralisation or inhibition less than 50, 25, 10, 5 or 0.5% inhibition or neutralisation of the most frequent TOI variant.","Clause 13: The method of any one of clauses 9 to 12, wherein the ligand is capable of binding to the most frequent TOI variant.","Clause 14: The method of any one of clauses 9 to 13, wherein the ligand is capable of binding to two or more different TOI variants, each being encoded by a nucleotide sequence having a cumulative human allele frequency of more than 50%.","In an embodiment, each TOI variant is encoded by a nucleotide sequence having a cumulative human allele frequency of 55, 60, 65, 70, 75, 80, 85 or 90 or more but less than 95, 96, 97, 98, 99 or 100% (eg, in the range from 51 to 80%).","In an embodiment, each TOI variant is encoded by a nucleotide sequence having a total human genotype frequency of 55, 60, 65, 70, 75, 80, 85 or 90 or more but less than 95, 96, 97, 98, 99 or 100% (eg, in the range from 51 to 80%).","Clause 15: The method of any preceding clause, wherein said variant nucleotide sequence recited in step (a) has been or is determined as being present in at least 2 different human ethnic populations, eg, at least 2, 3, 4, 5, 6, 7, 8 or 9 different human ethnic populations in Table 4.Clause 16: The method of any preceding clause, wherein said human frequency is the frequency in a database of naturally-occurring sequences sampled from at least 15, 20 or 25 different human ethnic populations and comprising at least 1000 sequences.","In an embodiment, the database is the 1000 Genomes Project database as described herein.","Clause 17: An anti-human TOI ligand for use in a method of treating and/or preventing a TOI-mediated disease or condition in a human, wherein the TOI is present in humans as different polymorphic variants and wherein the genome of said human comprises a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, the method comprising administering the ligand to the human.","In the alternative, clause 17 provides an anti-human TOI ligand for use in a method according to any one of clauses 1 to 16, the method comprising administering the ligand to the human.","In an embodiment, the cumulative human allele frequency is 30, 25, 20, 15, 10 or 5% or less, eg, in the range from 1 to 20% or 1 to 15% or 1 to 10%.","In an embodiment, the total human genotype frequency is 35, 30, 25, 20, 15, 10 or 5% or less, eg, in the range from 1 to 25%, 1 to 20%, 1 to 15%, 1 to about 15%, 1 to 10%, 1 to about 10% or 1 to 5% or 1 to about 5%.","Clause 18: The ligand of clause 17, wherein the ligand has been or is determined as capable of binding the human TOI encoded by said nucleotide sequence.","In the alternative, clause 18 provides a ligand that binds a human TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, for use in a method comprising the step of using the ligand to target said TOI in a human to treat and/or prevent a disease or condition mediated by TOI, the method comprising administering the ligand to the human.","Clause 19: A ligand that binds a human TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, for use in a method according to any one of clauses 1 to 16, the method comprising administering the ligand to the human.","Clause 20: The ligand of any one of clauses 17 to 19, wherein the human has been or is genotyped as positive for said TOI nucleotide sequence having a cumulative human allele frequency of less than 50%.","The ligand of any one of clauses 17 to 19, wherein the human has been or is genotyped as positive for said TOI nucleotide sequence having a total human genotype frequency of less than 50%.","Clause 21: The ligand of any one of clauses 17 to 20, wherein the human has been or is phenotyped as positive for a TOI encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.","Clause 22: The ligand of any one of clauses 17 to 21, wherein the human has been or is genotyped as heterozygous for a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%; optionally wherein the human has been or is genotyped as comprising a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and a TOI nucleotide sequence having a cumulative human allele frequency of more than 50% (eg, having the highest cumulative human allele frequency) and/or having a total human genotype frequency of more than 50% (eg, having the highest total human genotype frequency).","Clause 23: The ligand of any one of clauses 17 to 22, wherein the genome of the human has been or is genotyped as homozygous for a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.","Clause 24: The ligand of any one of clauses 17 to 23, wherein the ligand comprises an antibody binding site that binds a human TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%; and optionally has been or is determined as capable of such binding.","Clause 25: The ligand of clause 24, wherein the ligand is an antibody or antibody fragment.","Clause 26: The ligand of any one of clauses 17 to 23, wherein the ligand comprises a nucleotide sequence that specifically hybridises to a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50% or an RNA transcript thereof, and/or the ligand comprises a nucleotide sequence that comprises at least 10 contiguous nucleotides of a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50% or is an antisense sequence thereof.","In an embodiment, the ligand comprises a nucleotide sequence that comprises at least 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 50 or 100 contiguous nucleotides of a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50% or is an antisense sequence thereof.","Clause 27: The ligand of any one of clauses 17 to 26, wherein the genome of said human comprises a nucleotide sequence having a cumulative human allele frequency of less than 50% and the sequence is found in at least 2 different ethnic populations (eg, found in at least 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 different human ethnic populations (for example as per the populations in Table 4)).","In an example, numbers are with reference to the 1000 Genomes Project database.","The ligand of any one of clauses 17 to 26, wherein the genome of said human comprises a nucleotide sequence having a cumulative human allele frequency of less than 50% and the sequence is found in at least 20 individuals distributed across at least 2 said different ethnic populations (eg, found in at least in at least 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 130, 140 or 150 individuals distributed across such many different ethnic populations).","In an example, numbers are with reference to the 1000 Genomes Project database.","Clause 28: A pharmaceutical composition or kit for treating or preventing a condition or disease mediated by a TOI as recited in any preceding clause, the composition or kit comprising a ligand of any one of clauses 17 to 27; and optionally in combination with a label or instructions for use to treat and/or prevent said disease or condition in a human; optionally wherein the label or instructions comprise a marketing authorisation number (eg, an FDA or EMA authorisation number); optionally wherein the kit comprises an injection pen or IV container that comprises the ligand.","In an example, the label or instructions cover or describe use for a human comprising a TOI variant encoded by a nucleotide sequence as recited in clause 17.Clause 29: A method of producing an anti-human TOI antibody binding site, the method comprising obtaining a plurality of anti-TOI antibody binding sites, screening the antibody binding sites for binding to a TOI comprising an amino acid sequence encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, or to a peptide thereof that comprises an amino acid variation from the corresponding sequence encoded by the TOI-encoding nucleotide sequence having the highest cumulative human allele frequency and/or the highest total human genotype frequency, and isolating an antibody binding site that binds in the screening step.","In an embodiment of any aspect herein, the antibody, fragment or binding site is recombinant.","In the alternative, clause 29 provides: A method of producing an anti-human TOI antibody, the method comprising immunising a non-human vertebrate (eg, a mouse or a rat) with a TOI comprising an amino acid sequence encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, or to a peptide thereof that comprises an amino acid variation from the corresponding sequence encoded by the TOI-encoding nucleotide sequence having the highest cumulative human allele frequency and/or the highest total human genotype frequency, and isolating an antibody that binds a TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, and optionally producing a TOI-binding fragment or derivative of the isolated antibody.","The term “isolated” with reference to a ligand, antibody or protein, for example in any aspect, configuration, example or embodiment, means that a subject ligand, antibody, protein etc (1) is free of at least some other proteins with which it would normally be found, (2) is essentially free of other proteins from the same source, e.g., from the same species, (3) is expressed by a cell from a different species, (4) has been separated from at least about 50 percent of polynucleotides, lipids, carbohydrates, or other materials with which it is associated in nature, (5) is operably associated (by covalent or noncovalent interaction) with a polypeptide with which it is not associated in nature, or (6) does not occur in nature.","Typically, an “isolated” ligand, antibody, protein etc constitutes at least about 5%, at least about 10%, at least about 25%, or at least about 50% of a given sample.","Genomic DNA, cDNA, mRNA or other RNA, of synthetic origin, or any combination thereof can encode such an isolated ligand, antibody protein etc.","Preferably, the isolated ligand, antibody protein etc is substantially free from proteins or polypeptides or other contaminants that are found in its natural environment that would interfere with its therapeutic, diagnostic, prophylactic, research or other use.","For example, an “isolated” antibody is one that has been identified, separated and/or recovered from a component of its production environment (eg, naturally or recombinantly).","Preferably, the isolated polypeptide is free of association with all other components from its production environment, eg, so that the antibody has been isolated to an FDA-approvable or approved standard.","Contaminant components of its production environment, such as that resulting from recombinant transfected cells, are materials that would typically interfere with research, diagnostic or therapeutic uses for the antibody, and may include enzymes, hormones, and other proteinaceous or non-proteinaceous solutes.","In preferred embodiments, the polypeptide will be purified: (1) to greater than 95% by weight of antibody as determined by, for example, the Lowry method, and in some embodiments, to greater than 99% by weight; (2) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence by use of a spinning cup sequenator, or (3) to homogeneity by SDS-PAGE under non-reducing or reducing conditions using Coomassie blue or, preferably, silver stain.","Isolated antibody includes the antibody in situ within recombinant cells since at least one component of the antibody's natural environment will not be present.","Ordinarily, however, an isolated polypeptide or antibody will be prepared by at least one purification step.","Immunoconjugates The invention encompasses the ligand (eg, antibody) conjugated to a therapeutic moiety (“immunoconjugate”), such as a cytotoxin, a chemotherapeutic drug, an immunosuppressant or a radioisotope.","Cytotoxin agents include any agent that is detrimental to cells.","Examples of suitable cytotoxin agents and chemotherapeutic agents for forming immunoconjugates are known in the art, see for example, WO 05/103081.Bispecifics The antibodies of the present invention may be monospecific, bispecific, or multispecific.","Multispecific mAbs may be specific for different epitopes of one target polypeptide or may contain antigen-binding domains specific for more than one target polypeptide.","See, e.g., Tutt et al.","(1991) J. Immunol.","147:60-69.The human anti-TOI (eg, anti-PCSK9) mAbs can be linked to or co-expressed with another functional molecule, e.g., another peptide or protein.","For example, an antibody or fragment thereof can be functionally linked (e.g., by chemical coupling, genetic fusion, noncovalent association or otherwise) to one or more other molecular entities, such as another antibody or antibody fragment, to produce a bispecific or a multispecific antibody with a second binding specificity.","An exemplary bi-specific antibody format that can be used in the context of the present invention involves the use of a first immunoglobulin (Ig) CH3 domain and a second Ig CH3 domain, wherein the first and second Ig CH3 domains differ from one another by at least one amino acid, and wherein at least one amino acid difference reduces binding of the bispecific antibody to Protein A as compared to a bi-specific antibody lacking the amino acid difference.","In one embodiment, the first Ig CH3 domain binds Protein A and the second Ig CH3 domain contains a mutation that reduces or abolishes Protein A binding such as an H95R modification (by IMGT exon numbering; H435R by EU numbering).","The second CH3 may further comprise a Y96F modification (by IMGT; Y436F by EU).","Further modifications that may be found within the second CH3 include: D16E, L18M, N44S, K52N, V57M, and V821 (by IMGT; D356E, L358M, N384S, K392N, V397M, and V422I by EU) in the case of IgG1 antibodies; N44S, K52N, and V821 (IMGT; N384S, K392N, and V422I by EU) in the case of IgG2 antibodies; and Q15R, N44S, K52N, V57M, R69K, E79Q, and V821 (by IMGT; Q355R, N3845, K392N, V397M, R409K, E419Q, and V422I by EU) in the case of IgG4 antibodies.","Variations on the bi-specific antibody format described above are contemplated within the scope of the present invention.","Clause 30: The method of clause 29, comprising the step of obtaining a nucleic acid encoding the antibody, fragment, derivative or binding site and optionally inserting the nucleic acid in an expression vector.","Clause 31: A kit for TOI genotyping a human, wherein the kit comprises a nucleic acid comprising a nucleotide sequence that specifically hybridises to a TOI nucleotide sequence selected having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50% or an RNA transcript thereof, and/or the nucleic acid comprises a nucleotide sequence that comprises at least 10 (eg, at least 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 50 or 100) contiguous nucleotides of a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50% or is an antisense sequence thereof.","For example, the nucleic acid hybridises to a region immediately flanking a nucleotide that is variant compared to the corresponding nucleotide of the TOI nucleotide sequence having the highest cumulative human allele frequency and/or the highest total human genotype frequency.","In an example, the nucleic acid hybridises to at two or more such variant nucleotides.","Specific hybridisation is under stringent conditions, as will be apparent to the skilled person, eg, conditions of 5×SSC, 5×Denhardt's reagent, and 0.5% SDS at 65° C. Clause 32: A kit for TOI genotyping or phenotyping a human, wherein the kit comprises a ligand according to any one of clauses 17 to 27 or an antibody, fragment or derivative produced by the method of any one of clauses 29 to 31.For example, the ligand specifically binds to an epitope comprising an amino acid that is variant compared to the corresponding amino acid of the TOI encoded by a nucleotide sequence having the highest cumulative human allele frequency and/or the highest total human genotype frequency.","In an example, the ligand specifically binds to an epitope comprising two or more such variant amino acids.","In an example, specific binding means binding with an affinity (Kd) of 1 mM, 100 nM, 10 nM or 1 nM or less, eg, as determined by SPR.","The term “epitope” is a region of an antigen that is bound by an antibody.","Epitopes may be defined as structural or functional.","Functional epitopes are generally a subset of the structural epitopes and have those residues that directly contribute to the affinity of the interaction.","Epitopes may also be conformational, that is, composed of non-linear amino acids.","In certain embodiments, epitopes may include determinants that are chemically active surface groupings of molecules such as amino acids, sugar side chains, phosphoryl groups, or sulfonyl groups, and, in certain embodiments, may have specific three-dimensional structural characteristics, and/or specific charge characteristics.","Clause 33: Use of an anti-TOI ligand that binds a human TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, in the manufacture of a medicament for treating and/or preventing a TOI-mediated disease or condition in a human whose genome comprises a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.","Clause 34: Use of an anti-TOI ligand that binds a human TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, in the manufacture of a medicament for targeting said TOI in a human to treat and/or prevent a disease or condition mediated by TOI.","The use of clause 33 or 34, wherein the ligand, human, disease or condition is according to any one of clauses 1 to 27.Clause 35: A method of targeting a TOI for treating and/or preventing a TOI-mediated disease or condition in a human, the method comprising administering an anti-TOI ligand to a human comprising a TOI nucleotide sequence selected having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, whereby a TOI encoded by said nucleotide sequence is targeted.","Clause 36: The method of clause 35, wherein the method comprises targeting a human TOI comprising an amino acid sequence with said ligand to treat and/or prevent said disease or condition in said human, wherein said amino acid sequence is encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%.","Clause 37: A method of TOI genotyping a nucleic acid sample of a human, the method comprising identifying in the sample the presence of a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.","In an example, the method comprises obtaining a TOI nucleic acid sample from the human and then carrying out the identifying step.","Clause 38: A method of TOI typing a protein sample of a human, the method comprising identifying in the sample the presence of a TOI amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.","In an example, the method comprises obtaining a TOI protein sample from the human and then carrying out the identifying step.","Clause 39: The method of clause 37 or 38, comprising obtaining a sample of serum, blood, faeces, hair, urine or saliva from a human, whereby the nucleic acid or protein sample is obtained for use in the step of identifying said sequence.","Clause 40: The method of any one of clauses 37 to 39, comprising using a ligand according to any one of clauses 17 to 27 to carry out said identifying step.","Clause 41: A diagnostic kit comprising a ligand that is capable of binding a human TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50% and instructions for carrying out the method of clause 38 or 39.Clause 42: A diagnostic kit comprising a nucleic acid probe comprising a nucleotide sequence that specifically hybridises a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50% or an RNA transcript thereof and instructions for carrying out the method of clause 38 or 39.Clause 43: The method, ligand, composition, kit or use of any preceding clause, wherein the TOI is encoded by a nucleotide sequence having a cumulative human allele frequency from 1 to 10% and/or a total human genotype frequency from 1 to about 15% or from 1 to 15%.","Clause 44: The method, ligand, composition, kit or use of any preceding clause wherein the TOI is a human TOI selected from Table 5; optionally for treating and/or preventing a corresponding disease or condition as set out in Table 5.For example, the TOI is human PCSK9, eg, a mature, cleaved, autocatalysed or active PCSK9.In an example, the disease is a cardiovascular disease such as hyperlipidaemia.","Ligands of the invention are useful, for instance, in specific binding assays, for genotyping or phenotyping humans, affinity purification of the TOI and in screening assays to identify other antagonists of TOI activity.","Some of the ligands of the invention are useful for inhibiting binding of TOI to a congnate human receptor or protein, or inhibiting TOI-mediated activities.","The invention encompasses anti-TOI (eg, PCSK9) antibody ligands having a modified glycosylation pattern.","In some applications, modification to remove undesirable glycosylation sites may be useful, or e.g., removal of a fucose moiety to increase antibody dependent cellular cytotoxicity (ADCC) function (see Shield et al.","(2002) JBC 277:26733).","In other applications, modification of galactosylation can be made in order to modify complement dependent cytotoxicity (CDC).","In an example, the invention features a pharmaceutical composition comprising a ligand of the invention, wherein the ligand is or comprises a recombinant human antibody or fragment thereof which specifically binds the TOI (eg, a rare variant as described herein) and a pharmaceutically acceptable carrier.","In one embodiment, the invention features a composition which is a combination of an antibody ligand or antigen-binding fragment of an antibody of the invention, and a second therapeutic agent.","The second therapeutic agent may be any of an anti-inflammatory agent, an anti-angiogenesis agent, a painkiller, a diuretic, a chemotherapeutic agent, an anti-neoplastic agent, a vasodilator, a vasoconstrictor, a statin, a beta blocker, a nutrient, an adjuvant, an anti-obesity agent and an anti-diabetes agent.","“Pharmaceutically acceptable” refers to approved or approvable by a regulatory agency of the USA Federal or a state government or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in animals, including humans.","A “pharmaceutically acceptable carrier, excipient, or adjuvant” refers to an carrier, excipient, or adjuvant that can be administered to a subject, together with an agent, e.g., any antibody or antibody chain described herein, and which does not destroy the pharmacological activity thereof and is nontoxic when administered in doses sufficient to deliver a therapeutic amount of the agent.","In an example, the invention features a method for inhibiting TOI activity using the anti-TOI ligand of the invention (eg, an antibody or antigen-binding portion of the antibody of the invention), wherein the therapeutic method comprises administering a therapeutically effective amount of a pharmaceutical composition comprising the ligand.","The disorder treated is any disease or condition which is improved, ameliorated, inhibited or prevented by removal, inhibition or reduction of TOI activity.","By the phrase “therapeutically effective amount” is meant an amount that produces the desired effect for which it is administered.","The exact amount will depend on the purpose of the treatment, and will be ascertainable by one skilled in the art using known techniques (see, for example, Lloyd (1999) The Art, Science and Technology of Pharmaceutical Compounding).","The term “specifically binds,” or the like, means that a ligand, eg, an antibody or antigen-binding fragment thereof, forms a complex with an antigen that is relatively stable under physiologic conditions.","Specific binding can be characterized by an equilibrium dissociation constant of at least about 1×10−6 M or less (e.g., a smaller KD denotes a tighter binding).","Methods for determining whether two molecules specifically bind are well known in the art and include, for example, equilibrium dialysis, surface plasmon resonance, and the like.","An isolated antibody that specifically binds a human TOI may, however, exhibit cross-reactivity to other antigens such as a TOI molecule from another species.","Moreover, multi-specific antibodies (e.g., bispecifics) that bind to human TOI and one or more additional antigens are nonetheless considered antibodies that “specifically bind” TOI, as used herein.","Genotyping & Phenotyping The skilled person will be familiar with techniques that can be used for accurate genotyping and application to the invention.","These include the following.","1 Hybridization-based methods 1.1 Dynamic allele-specific hybridization 1.2 Molecular beacons 1.3 SNP microarrays 2 Enzyme-based methods 2.1 Restriction fragment length polymorphism 2.2 PCR-based methods 2.3 Flap endonuclease 2.4 Primer extension 2.5 5′-nuclease 2.6 Oligonucleotide Ligation Assay 3 Other post-amplification methods based on physical properties of DNA 3.1 Single strand conformation polymorphism 3.2 Temperature gradient gel electrophoresis 3.3 Denaturing high performance liquid chromatography 3.4 High-resolution melting of the entire amplicon 3.5 Use of DNA mismatch-binding proteins 3.6 SNPlex (SNPlex™ is a proprietary genotyping platform sold by Applied Biosystems).","Next-generation sequencing technologies such as pyrosequencing is also useful.","Reference is also made to GB2444410A and the genotyping method disclosed therein, which is incorporated herein by reference in its entirety.","Miniaturized assays, such as microarrays with oligonucleotide reagents immobilized on small surfaces, are frequently proposed for large-scale mutation analysis and high-throughput genotyping (Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome (Wang D G, Fan J B, Siao C J, Berno A, Young P, Sapolsky R, Ghandour G, Perkins N, Winchester E, Spencer J, Kruglyak L, Stein L, Hsie L, Topaloglou T, Hubbell E, Robinson E, Mittmann M, Morris M S, Shen N, Kilburn D, Rioux J, Nusbaum C, Rozen S, Hudson T J, Lipshutz R, Chee M, Lander E S, Science.","1998 May 15; 280(5366): 1077-82).","Other high-throughput methods discriminate alleles by differential hybridization, primer extension, ligation and cleavage of an allele-specific probe (Review Accessing genetic variation: genotyping single nucleotide polymorphisms, Syvainen A C, Nat Rev Genet.","2001 December; 2(12):930-42; Review Techniques patents for SNP genotyping, Twyman R M, Primrose S B, Pharmacogenomics.","2003 January; 4(1):67-79).","An approach for a fully automated, large-scale SNP analysis is the ‘homogeneous’ assay, i.e.","a single-phase assay without separation steps, permitting continual monitoring during amplification.","The TaqMan™ assay (Applied Biosystems), originally designed for quantitative real-time PCR, is a homogeneous, single-step assay also used in determination of mutation status of DNA (see, eg, A.","A. Komar (ed.","), Single Nucleotide Polymorphisms, Methods in Molecular Biology 578, DOI 10.1007/978-1-60327-411-1_19, Humana Press, a part of Springer Science+Business Media, LLC; and Single Nucleotide Polymorphisms, Methods in Molecular Biology™ Volume 578, 2009, pp 293-306, The TaqMan Method for SNP Genotyping, Gong-Qing Shen et al).","The TaqMan SNP Genotyping Assay exploits the 5′-exonuclease activity of AmpliTaq Gold™ DNA polymerase to cleave a doubly labeled probe hybridized to the SNP-containing sequence of ssDNA.","Cleavage separates a 5′-fluorophore from a 3′-quencher leading to detectable fluorescent signal.","The use of two allele-specific probes carrying different fluorophores permits SNP determination in the same tube without any post-PCR processing.","Genotype is determined from the ratio of intensities of the two fluorescent probes at the end of amplification.","Thus, rather than taking advantage of the full set of real-time PCR data as in quantitative studies, only end-point data are used.","TaqMan SNP genotyping in a high-throughput, automated manner is facilitated by the use of validated Pre-made TaqMan® Genotyping assays, but Custom TaqMan® Assays may also be used (High-throughput genotyping with single nucleotide polymorphisms, Ranade K, Chang M S, Ting C T, Pei D, Hsiao C F, Olivier M, Pesich R, Hebert J, Chen Y D, Dzau V J, Curb D, Olshen R, Risch N, Cox D R, Botstein D, Genome Res.","2001 July; 11(7): 1262-8; Assessment of two flexible and compatible SNP genotyping platforms: TaqMan SNP Genotyping Assays and the SNPlex Genotyping System, De la Vega F M, Lazaruk K D, Rhodes M D, Wenz M H, Mutat Res.","2005 Jun.","3; 573(1-2): 111-35).","The results of the assay can be automatically determined by genotyping software provided with real-time thermal cyclers (e.g.","IQ software of Bio-Rad, Sequence Detection Software of Applied Biosystems).","Single nucleotide polymorphisms (SNPs) can be determined using TaqMan™ real-time PCR assays (Applied Biosystems) and commercial software that assigns genotypes based on reporter probe signals at the end of amplification.","An algorithm for automatic genotype calling of SNPs using the full course of TaqMan real-time data is available for use (A. Callegaro et al, Nucleic Acids Res.","2006; 34(7): e56, Published online 2006 Apr.","14.doi: 10.1093/nar/gk1185, PMCID: PMC1440877).","The algorithm is unique in that it classifies samples according to the behavior of blanks (no DNA samples), which cluster with heterozygous samples.","This method of classification eliminates the need for positive controls and permits accurate genotyping even in the absence of a genotype class, for example when one allele is rare.","The skilled person will be familiar with techniques that can be used for accurate phenotyping and application to the invention.","These include the use of amino acid sequencing of isolated target protein and comparison of sequences from different variants (eg, with the most common variant).","An antibody that specifically and selectively binds in the area of a SNP under stringent conditions can also be used to identify a particular variant.","In another method, the genotype is determined and a corresponding amino acid sequence (phenotype) determined, eg, by in silico translation.","Therapeutic Administration and Formulations The invention provides therapeutic compositions comprising the anti-TOI ligand, eg, antibodies or antigen-binding fragments thereof, of the present invention.","The administration of therapeutic compositions in accordance with the invention will be administered with suitable carriers, excipients, and other agents that are incorporated into formulations to provide improved transfer, delivery, tolerance, and the like.","A multitude of appropriate formulations can be found in the formulary known to all pharmaceutical chemists: Remington's Pharmaceutical Sciences, Mack Publishing Company, Easton, Pa.","These formulations include, for example, powders, pastes, ointments, jellies, waxes, oils, lipids, lipid (cationic or anionic) containing vesicles (such as LIPOFECTINT™), DNA conjugates, anhydrous absorption pastes, oil-in-water and water-in-oil emulsions, emulsions carbowax (polyethylene glycols of various molecular weights), semi-solid gels, and semi-solid mixtures containing carbowax.","See also Powell et al.","“Compendium of excipients for parenteral formulations” PDA (1998) J Pharm Sci Technol 52:238-311.The dose may vary depending upon the age and the size of a subject to be administered, target disease, conditions, route of administration, and the like.","When the ligand, eg, antibody, of the present invention is used for treating various conditions and diseases associated with the TOI in an adult patient, it is advantageous to intravenously administer the antibody of the present invention normally at a single dose of about 0.01 to about 20 mg/kg body weight, more preferably about 0.02 to about 7, about 0.03 to about 5, or about 0.05 to about 3 mg/kg body weight.","Depending on the severity of the condition, the frequency and the duration of the treatment can be adjusted.","Various delivery systems are known and can be used to administer the ligand or pharmaceutical composition of the invention, for example a ligand provided by e.g., encapsulation in liposomes, microparticles, microcapsules, recombinant cells capable of expressing the mutant viruses, receptor mediated endocytosis (see, e.g., Wu et al.","(1987) J. Biol.","Chem.","262:4429-4432).","Methods of introduction include, but are not limited to, intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal, epidural, and oral routes.","The ligand or composition may be administered by any convenient route, for example by infusion or bolus injection, by absorption through epithelial or mucocutaneous linings (e.g., oral mucosa, rectal and intestinal mucosa, etc.)","and may be administered together with other biologically active agents.","Administration can be systemic or local.","The ligand or pharmaceutical composition can be also delivered in a vesicle, in particular a liposome (see Langer (1990) Science 249:1527-1533; Treat et al.","(1989) in Liposomes in the Therapy of Infectious Disease and Cancer, Lopez Berestein and Fidler (eds.","), Liss, New York, pp.","353-365; Lopez-Berestein, ibid., pp.","317-327; see generally ibid.).","In certain situations, the ligand or pharmaceutical composition can be delivered in a controlled release system.","In one embodiment, a pump may be used (see Langer, supra; Sefton (1987) CRC Crit.","Ref.","Biomed.","Eng.","14:201).","In another embodiment, polymeric materials can be used; see, Medical Applications of Controlled Release, Langer and Wise (eds.","), CRC Pres., Boca Raton, Fla. (1974).","In yet another embodiment, a controlled release system can be placed in proximity of the composition's target, thus requiring only a fraction of the systemic dose (see, e.g., Goodson, in Medical Applications of Controlled Release, supra, vol.","2, pp.","115-138, 1984).","The injectable preparations may include dosage forms for intravenous, subcutaneous, intracutaneous and intramuscular injections, drip infusions, etc.","These injectable preparations may be prepared by methods publicly known.","For example, the injectable preparations may be prepared, e.g., by dissolving, suspending or emulsifying the antibody or its salt described above in a sterile aqueous medium or an oily medium conventionally used for injections.","As the aqueous medium for injections, there are, for example, physiological saline, an isotonic solution containing glucose and other auxiliary agents, etc., which may be used in combination with an appropriate solubilizing agent such as an alcohol (e.g., ethanol), a polyalcohol (e.g., propylene glycol, polyethylene glycol), a nonionic surfactant [e.g., polysorbate 80, HCO-50 (polyoxyethylene (50 mol) adduct of hydrogenated castor oil)], etc.","As the oily medium, there are employed, e.g., sesame oil, soybean oil, etc., which may be used in combination with a solubilizing agent such as benzyl benzoate, benzyl alcohol, etc.","The injection thus prepared is preferably filled in an appropriate ampoule.","A pharmaceutical composition of the present invention can be delivered subcutaneously or intravenously with a standard needle and syringe.","In addition, with respect to subcutaneous delivery, a pen delivery device readily has applications in delivering a pharmaceutical composition of the present invention.","Such a pen delivery device can be reusable or disposable.","A reusable pen delivery device generally utilizes a replaceable cartridge that contains a pharmaceutical composition.","Once all of the pharmaceutical composition within the cartridge has been administered and the cartridge is empty, the empty cartridge can readily be discarded and replaced with a new cartridge that contains the pharmaceutical composition.","The pen delivery device can then be reused.","In a disposable pen delivery device, there is no replaceable cartridge.","Rather, the disposable pen delivery device comes prefilled with the pharmaceutical composition held in a reservoir within the device.","Once the reservoir is emptied of the pharmaceutical composition, the entire device is discarded.","Numerous reusable pen and autoinjector delivery devices have applications in the subcutaneous delivery of a ligand or pharmaceutical composition of the present invention.","Examples include, but certainly are not limited to AUTOPEN™ (Owen Mumford, Inc., Woodstock, UK), DISETRONIC™ pen (Disetronic Medical Systems, Burghdorf, Switzerland), HUMALOG MIX 75/25™ pen, HUMALOG™ pen, HUMALIN 70/30™ pen (Eli Lilly and Co., Indianapolis, Ind.","), NOVOPEN™ I, II and III (Novo Nordisk, Copenhagen, Denmark), NOVOPEN JUNIOR™ (Novo Nordisk, Copenhagen, Denmark), BD™ pen (Becton Dickinson, Franklin Lakes, N.J.), OPTIPENT™, OPTIPEN PRO™, OPTIPEN STARLET™, and OPTICLIKT™ (sanofi-aventis, Frankfurt, Germany), to name only a few.","Examples of disposable pen delivery devices having applications in subcutaneous delivery of a pharmaceutical composition of the present invention include, but certainly are not limited to the SOLOSTAR™ pen (sanofi-aventis), the FLEXPEN™ (Novo Nordisk), and the KWIKPEN™ (Eli Lilly).","Advantageously, the pharmaceutical compositions for oral or parenteral use described above are prepared into dosage forms in a unit dose suited to fit a dose of the ligand(s).","Such dosage forms in a unit dose include, for example, tablets, pills, capsules, injections (ampoules), suppositories, etc.","The amount of the aforesaid antibody contained is generally about 5 to about 500 mg per dosage form in a unit dose; especially in the form of injection, it is preferred that the aforesaid antibody is contained in about 5 to about 100 mg and in about 10 to about 250 mg for the other dosage forms.","Exemplary TOIs For example in any configuration, aspect, concept, example or configuration of the invention, the or each TOI is selected from the group consisting of ABCF1; ACVR1; ACVR1B; ACVR2; ACVR2B; ACVRL1; ADORA2A; Aggrecan; AGR2; AICDA; AW1; AIG1; AKAP1; AKAP2; AIYIH; amyloid-beta; AMHR2; ANGPT1; ANGPT2; ANGPTL3; ANGPTL4; ANPEP; APC; APOC1; AR; Axl; AZGP1 (zinc-a-glycoprotein); B7.1; B7.2; BAD; BAFF; BAG1; BAI1; BCL2; BCL6; BDNF; BLNK; BLR1 (MDR15); BlyS; BMP1; BMP2; BMP3B (GDF1O); BMP4; BMP6; BMP8; BMPR1A; BMPR1B; BMPR2; BPAG1 (plectin); BRCA1; C19orflO (IL27w); C3; C4A; C5; C5R1; CANT1; CASP1; CASP4; CAV1; CB1; CCBP2 (D6/JAB61); CCL1 (I-309); CCL11 (eotaxin); CCL13 (MCP-4); CCL15 (MIP-id); CCL16 (HCC-4); CCL17 (TARC); CCL18 (PARC); CCL19 (MIP-3b); CCL2 (MCP-1); MCAF; CCL2O (MIP-3a); CCL21 (MIP-2); SLC; exodus-2; CCL22 (MDC/STC-1); CCL23 (MPIF-1); CCL24 (MPIF-2 I eotaxin-2); CCL25 (TECK); CCL26 (eotaxin-3); CCL27 (CTACK/ILC); CCL28; CCL3 (MIP-1a); CCL4 (MIP-1b); CCL5 (RANTES); CCL7 (MCP-3); CCL8 (mcp-2); CCNA1; CCNA2; CCND1; CCNE1; CCNE2; CCR1 (CKR1/HM145); CCR2 (mcp-1RB/RA); CCR3 (CKR3/CMKBR3); CCR4; CCR5 (CMKBR5/ChemR13); CCR6 (CMKBR6/CKR-L3/STRL22/DRY6); CCR7 (CKR7/EBI1); CCR8 (CMKBR8/TER1/CKR-L1); CCR9 (GPR-9-6); CCRL1 (VSHK1); CCRL2 (L-CCR); CD7, CD164; CD19; CD1C; CD20; CD200; CD-22; CD24; CD28; CD3; CD37; CD38; CD3E; CD3G; CD3Z; CD4; CD40; CD40L; CD44; CD45RB; CD52; CD69; CD72; CD74; CD79A; CD79B; CD8; CD8O; CD81; CD83; CD86; CD96; CD207; CDH1 (E-cadherin); CDH10; CDH12; CDH13; CDH18; CDH19; CDH20; CDH5; CDH7; CDH8; CDH9; CDK2; CDK3; CDK4; CDK5; CDK6; CDK7; CDK9; CDKN1A (p21Wap1/Cip1); CDKN1B (p27Kip1); CDKNIC; CDKN2A (p161NK4a); CDKN2B; CDKN2C; CDKN3; CEBPB; CELSR3; CER1; CHGA; CHGB; Chitinase; CHRNG; CHST10; CKLFSF2; CKLFSF3; CKLFSF4; CKLFSF5; CKLFSF6; CKLFSF7; CKLFSF8; CLDN3; CLDN7 (claudin-7); CLN3; CLU (clusterin); CMKLR1; CMKOR1 (RDC1); CNR1; COL18A1; COL1A1; COL4A3; COL6A1; CR2; CRP; CSF1 (M-CSF); CRLF2; CSF2 (GM-CSF); CSF3 (GCSF); CTLA4; CTNNB1 (b-catenin); CTSB (cathepsin B); CX3CL1 (SCYDi); CX3CR1 (V28); CXCR6; CXCL1 (GRO1); CXCL10 (IP-10); CXCL11 (I-TAC/IP-9); CXCL12 (SDF1); CXCL13; CXCL14; CXCL16; CXCL2 (GRO2); CXCL3 (GRO3); CXCL5 (ENA-78 I LIX); CXCL6 (GCP-2); CXCL9 (MIG); CXCR3 (GPR9/CKR-L2); CXCR4; CXCR6 (TYMSTR ISTRL33 I Bonzo); CYB5; CYC1; CYSLTR1; DAB2IP; DAND5; DES; DKFZp451J0118; DNCL1; DPP4; E2F1; ECGF1; EDG1; EFNAI; EFNA3; EFNB2; EGF; EGFR; ELAC2; ENG; ENO1; ENO2; ENO3; EphA4; EPHB4; EPO; ERBB2 (Her-2); EREG; ERK8; ESR1; ESR2; F3 (TF); FADD; FasL; FASN; FCER1A; FCER2; FCGR3A; FCRL4; FGF; FGF1 (aFGF); FGF10; FGF11; FGF12; FGF12B; FGF13; FGF14; FGF16; FGF17; FGF18; FGF19; FGF2 (bFGF); FGF20; FGF21; FGF22; FGF23; FGF3 (int-2); FGF4 (HST); FGF5; FGF6 (HST-2); FGF7 (KGF); FGF8; FGF9; FGFR3; FIGF (VEGFD); FIL1 (EPSILON); FIL1 (ZETA); FLJ12584; FLJ25530; FLRT1 (fibronectin); FLT1; FOS; FOSL1 (FRA-1); FY (DARC); GABRP (GABAa); GAGEB1; GAGEC1; Galectin-3; GALNAC4S-65T; GATA3; GDF5; GFI1; GGT1; GHR; GM-CSF; GNAS1; GNRH1; GPR2 (CCR1O); GPR31; GPR44; GPR81 (FKSG8O); GPR87; GPR137C; GRCC10 (C10); GRP; GSN (Gelsolin); GSTP1; HAVCR1; HAVCR2; HDAC4; EDAC5; HDAC7A; HDAC9; hepcidin; hemojuvelin; HGF; HIF1A; HIP1; histamine and histamine receptors; HLA-A; HLA-DRA; HM74; HMOX1; HUMCYT2A; ICEBERG; ICOS; 1D2; IFN-a; IFNA1; IFNA2; IFNA4; IFNA5; IFNA6; IFNA7; IFNB1; IFNgamma; TFNW1; IGBP1; IGF1; IGF1R; IGF2; IGFBP2; IGFBP3; IGFBP6; IL-1; IL10; IL10RA; IL10RB; IL11; IL11RA; IL-12; IL12A; IL12B; IL12RB1; IL12RB2; 1L13; IL13RA1; IL13RA2; 1L14; 1L15; IL15RA; IL16; 1L17; IL17B; IL17C; IL17R; 1L18; IL18BP; IL18R1; IL18RAP; 1L19; IL1A; IL1B; IL1F10; IL1F5; IL1F6; IL1F7; IL1F8; IL1F9; IL1HY1; IL1R1; IL1R2; IL1RAP; IL1RAPL1; IL1RAPL2; IL1RL1; IL1RL2 IL1RN; 1L2; 1L20; IL20RA; IL21R; 1L22; 1L22R; 1L22RA2; 1L23; 1L24; 1L25; 1L26; 1L27; 1L28A; 1L28B; 1L29; IL2RA; IL2RB; IL2RG; 1L3; 1L30; IL3RA; 1L4; IL4R; 1L5; IL5RA; 1L6; IL6 receptor; IL6ST (glycoprotein 130); 1L7; TL7R; 1L8; IL8RA; IL8RB; IL8RB; 1L9; IL9R; ILK; INHA; INHBA; INSL3; INSL4; IRAK1; IRAK2; ITGA1; ITGA2; 1TGA3; ITGA6 (a6 integrin); ITGAV; ITGB3; ITGB4 (b 4 integrin); JAG1; JAK1; JAK3; JUN; K6HF; KAI1; KDR; MTLG; KLF5 (GC Box BP); KLF6; KLK10; KLK12; KLK13; KLK14; KLK15; KLK3; KLK4; KLK5; KLK6; KLK9; KRT1; KRT19 (Keratin 19); KRT2A; KRTHB6 (hair-specific type II keratin); LAG3; LAMA5; LEP (leptin); LIGHT; Lingo-p75; Lingo-Troy; LPS; LRP5; LTA (TNF-b); LTB; LTB4R (GPR16); LTB4R2; LTBR; MACMARCKS; MAG or Omgp; MAP2K7 (c-Jun); MDK; MIB1; midkine; MIF; MIP-2; MK167 (Ki-67); MMP2; MMP9; MS4A1; MSMB; MT3 (metallothionectin-ifi); MTSS 1; MUC 1 (mucin); MYC; MYD88; NCK2; neurocan; Nav1.7; Nav1.8; NFKB1; NFKB2; NGFB (NGF); NGFR; NgR-Lingo; NgR-Nogo66 (Nogo); NgR-p75; NgR-Troy; NME1 (NM23A); NOX5; NPPB; NROB1; NROB2; NR1D1; NR1D2; NR1H2; NR1H3; NR1H4; NR1I2; NR1I3; NR2C1; NR2C2; NR2E1; NR2E3; NR2F1; NR2F2; NR2F6; NR3C1; NR3C2; NR4A1; NR4A2; NR4A3; NR5A1; NR5A2; NR6A1; NRP1; NRP2; NT5E; NTN4; ODZ1; OPG; OPRD1; OX40L; OX40; P2RX7; PAP; PART1; PATE; PAWR; PCA3; PCNA; PCSK9, PD-1, PD-L1; PDGFA; PDGFB; PECAM1; PF4 (CXCL4); PGF; PGR; phosphacan; PIAS2; Placental Growth Factor (PIGF); PIK3CG; PLAU (uPA); PLG; PLXDC1; PPBP (CXCL7); PPID; PR1; PRKCQ; PRKD1; PRL; PROC; PROK2; PSAP; PSCA; PTAFR; PTEN; PTGS2 (COX-2); PTN; RAC2 (p21Rac2); RARB; RGS1; RGS13; RGS3; RNF110 (ZNF144); ROBO2; ROR1; S100A2; SCGB1D2 (lipophilin B); SCGB2A1 (mammaglobin 2); SCGB2A2 (mammaglobin 1); SCYE1 (endothelial Monocyte-activating cytokine); SDF2; SERPINA1; SERPINIA3; SERPINB5 (maspin); SERPINE1 (PAT-i); SERPINF1; SHBG; SLA2; SLC2A2; SLC33A1; SLC43A1; SLIT2; SPP1; SPRR1B (Spri); ST6GAL1; STAB1; STAT6; STEAP; STEAP2; TB4R2; TBX21; TCP1O; TDGF1; TEK; TGFA; TGFB1; TGFBII1; TGFB2; TGFB3; TGFBI; TGFBR1; TGFBR2; TGFBR3; TH1L; THBS1 (thrombospondin-1); THBS2; THBS4; THPO; TIE (Tie-i); TIM3; TMP3; tissue factor; TLR1O; TLR2; TLR3; TLR4; TLR5; TLR6; TLR7; TLR8; TLR9; TMPRSS6; TNF; TNF-a; TNFAIP2 (B94); TNFAIP3; TNFRSF1 1A; TNFRSF1A; TNFRSFiB; TNFRSF21; TNFRSF5; TNFRSF6 (Fas); TNFRSF7; TNFRSF8; TNFRSF9; TNFSF1O (TRAIL); TNFSF1 1 (TRANCE); TNFSF12 (APO3L); TNFSF13 (April); TNFSF13B; TNFSF14 (HVEM-L); TNFSF1 5 (VEGI); TNFSF1 8; TNFSF4 (0X40 ligand); TNFSF5 (CD4O ligand); TNFSF6 (FasL); TNFSF7 (CD27 ligand); TNFSF8 (CD3O ligand); TNFSF9 (4-1BB ligand); TOLLIP; Toll-like receptors; TOP2A (topoisomerase lia); TP53; TPM1; TPM2; TRADD; TRAF1; TRAF2; TRAF3; TRAF4; TRAF5; TRAF6; TRAIL; TREM1; TREM2; TRPC6; TSLP; TWEAK; VEGFA; VEGFB; VEGFC; versican; VHL C5; VLA-4; Wnt7A; XCL1 (lymphotactin); XCL2 (SCM-lb); XCR1 (GPR5/CCXCR1); YY1; and ZFPM2.In an example, the TOI is a human TOI selected from Table 5.In an example, the TOI is OX40 ligand.","In an example, the TOI is OX40.In an example, the TOI is PCSK9.In an example, the TOI is IL6 receptor (IL-6R).","In an example, the TOI is LIGHT.","In an example, the TOI is VEGF-A.","In an example, the TOI is TNF alpha.","In an example, the TOI is PIGF.","In an example, the TOI is IGF1R.","In an example, the TOI is OPG.","In an example, the TOI is ICOS In an example, the TOI is NGF.","In an example, the TOI is BMP6.In an example, the TOI is ferroportin.","In an example, the TOI is TMPRSS6.In an example, the TOI is hemojuvelin.","In an example, the TOI is VEGF receptor.","In an example, the TOI is PDGF receptor.","In an example, the TOI is stem cell factor receptor.","In an example, the TOI is hepcidin.","In an example, the TOI is IL-4 receptor alpha.","In an example, the TOI is sclerostin.","In an example, the TOI is IL-13 receptor.","In an example, the TOI is CD7.In an example, the TOI is delta-like ligand-4 (Dll4).","In an example, the TOI is HGF.","In an example, the TOI is angiopoietin-2 (Ang2).","In an example, the TOI is GDF8.In an example, the TOI is ERBB3.In an example, the TOI is IL-17 receptor.","In an example, the TOI is CD40.In an example, the TOI is CD40 ligand.","In an example, the TOI is EGFR.","For convenience, the meaning of some terms and phrases used in the specification, examples, and appended claims, are provided below.","Unless stated otherwise, or implicit from context, the following terms and phrases include the meanings provided below.","The definitions are provided to aid in describing particular embodiments, and are not intended to limit the claimed invention, because the scope of the invention is limited only by the claims.","Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.","If there is an apparent discrepancy between the usage of a term in the art and its definition provided herein, the definition provided within the specification shall prevail.","For convenience, certain terms employed herein, in the specification, examples and appended claims are collected here.","The terms “decrease”, “reduced”, or “reduction” are all used herein to mean a decrease by a statistically significant amount.","In some embodiments, “reduce,” “reduction” or “decrease” typically means a decrease by at least 10% as compared to a reference level (e.g.","the absence of a given treatment) and can include, for example, a decrease by at least about 10%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, or more.","As used herein, “reduction” does not encompass a complete reduction as compared to a reference level.","A decrease can be preferably down to a level accepted as within the range of normal for an individual without a given disorder.","However, for example, for the purposes of lowering or reducing cholesterol level, for example, a reduction by about 5-10 points can be considered a “decrease” or “reduction.” In certain aspects of all embodiments of the invention, the term “inhibition” is used.","Inhibition refers and refers to decrease by at least 10% as compared to a reference level (e.g.","the absence of a given treatment) and can include, for example, a decrease by at least about 10%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, or more including 100% inhibition as compared to a reference level.","“Complete inhibition” refers to a 100% inhibition as compared to a reference level.","The terms “increased”, “increase”, “enhance”, or “activate” are all used herein to mean an increase by a statically significant amount.","In some embodiments, the terms “increased”, “increase”, “enhance”, or “activate” can mean an increase of at least 10% as compared to a reference level, for example an increase of at least about 20%, or at least about 30%, or at least about 40%, or at least about 50%, or at least about 60%, or at least about 70%, or at least about 80%, or at least about 90% or up to and including a 100% increase or any increase between 10-100% as compared to a reference level, or at least about a 2-fold, or at least about a 3-fold, or at least about a 4-fold, or at least about a 5-fold or at least about a 10-fold increase, or any increase between 2-fold and 10-fold or greater as compared to a reference level.","In the context of a marker or symptom, an “increase” is a statistically significant increase in such level.","As used herein, the term “substantially” refers to the qualitative condition of exhibiting total or near-total extent or degree of a characteristic or property of interest.","One of ordinary skill in the biological arts will understand that biological and chemical phenomena rarely, if ever, go to completion and/or proceed to completeness or achieve or avoid an absolute result.","The term “substantially” is therefore used herein to capture the potential lack of completeness inherent in many biological and chemical phenomena.","For the removal of doubt, “substantially” can refer to at least a 90% extent or degree of a characteristic or property of interest, e.g.","at least 90%, at least 92%, at least 95%, at least 98%, at least 99% or greater.","As used herein, a “subject” means a human or animal.","Usually the animal is a vertebrate such as a primate, rodent, domestic animal or game animal.","Primates include chimpanzees, cynomologous monkeys, spider monkeys, and macaques, e.g., Rhesus.","Rodents include mice, rats, woodchucks, ferrets, rabbits and hamsters.","In some embodiments, the subject is a mammal, e.g., a primate, e.g., a human.","The terms, “individual,” “patient” and “subject” are used interchangeably herein.","In some embodiments, the subject can be a non-human vertebrate, e.g.","a primate, a rodent, a mouse, a rat, a pig, a sheep, a zebrafish, a frog, etc.","Preferably, the subject is a mammal.","The mammal can be a human, non-human primate, mouse, rat, dog, cat, horse, or cow, but is not limited to these examples.","Mammals other than humans can be advantageously used as subjects that represent animal models of a disease or condition, e.g., a cardiovascular condition.","A subject can be male or female.","A subject can be one who has been previously diagnosed with or identified as suffering from or having a condition in need of treatment or one or more complications related to such a condition, and optionally, have already undergone treatment for the condition or the one or more complications related to the condition.","Alternatively, a subject can also be one who has not been previously diagnosed as having the condition or one or more complications related to the condition.","For example, a subject can be one who exhibits one or more risk factors for the condition or one or more complications related to the condition or a subject who does not exhibit risk factors.","A “subject in need” or “human in need” of treatment for a particular condition can be a subject having that condition, such as increased cholesterol levels, diagnosed as having that condition, or at risk of developing that condition.","As used herein, the terms “protein” and “polypeptide” are used interchangeably herein to designate a series of amino acid residues, connected to each other by peptide bonds between the alpha-amino and carboxy groups of adjacent residues.","The terms “protein”, and “polypeptide” refer to a polymer of amino acids with natural amino acids.","When referring to “modified polypeptides” one refers to polypeptides that include modified amino acids (e.g., phosphorylated, glycated, glycosylated, etc.)","and amino acid analogs, regardless of its size or function.","“Protein” and “polypeptide” are often used in reference to relatively large polypeptides, whereas the term “peptide” is often used in reference to small polypeptides, but usage of these terms in the art overlaps.","The terms “protein” and “polypeptide” are used interchangeably herein when referring to a gene product and fragments thereof.","Thus, exemplary polypeptides or proteins include gene products, naturally occurring proteins with the specified sequence.","One can also use peptide homologs, peptide orthologs, peptide paralogs, peptide fragments and other equivalents, variants, fragments, and analogs of the peptides as these terms are understood by one of ordinary skill in the art.","As used herein, the term “nucleic acid” or “nucleic acid sequence” refers to any molecule, preferably a polymeric molecule, incorporating units of ribonucleic acid, deoxyribonucleic acid.","The nucleic acid can be either single-stranded or double-stranded.","A single-stranded nucleic acid can be one nucleic acid strand of a denatured double-stranded DNA.","Alternatively, it can be a single-stranded nucleic acid not derived from any double-stranded DNA.","In one aspect, the nucleic acid can be DNA.","In another aspect, the nucleic acid can be RNA.","Suitable nucleic acid molecules are DNA, including genomic DNA or cDNA.","Other suitable nucleic acid molecules are RNA, including mRNA.","In some aspects one can also use analogs of nucleic acids.","As used herein, the term “nucleic acid probe” refers to an isolated oligonucleotide molecule having a nucleic acid sequence which can hybridize to a target nucleic acid sequence, e.g.","specifically hybridize to the target sequence.","In some embodiments, a nucleic acid probe can further comprise a detectable label.","In some embodiments, a nucleic acid probe can be attached to a solid surface.","In some embodiments, a nucleic acid from is from about 5 nt to about 100 nt in length.","As used herein, the term “siRNA” refers to a nucleic acid that forms an RNA molecule comprising two individual strands of RNA which are substantially complementary to each other.","Typically, the siRNA is at least about 15-40 nucleotides in length (e.g., each complementary sequence of the double stranded siRNA is about 15-40 nucleotides in length, and the double stranded siRNA is about 15-40 base pairs in length, preferably about 19-25 base nucleotides, e.g., 19, 20, 21, 22, 23, 24, or 25 nucleotides in length).","In some embodiments, a siRNA can be blunt-ended.","In some embodiments, a siRNA can comprise a 3′ and/or 5′ overhang on each strand having a length of about 0, 1, 2, 3, 4, or 5 nucleotides.","The length of the overhang is independent between the two strands, i.e., the length of the overhang on one strand is not dependent on the length of the overhang on the second strand.","The siRNA molecules can also comprise a 3′ hydroxyl group.","In some embodiments, the siRNA can comprise a 5′ phosphate group.","A siRNA has the ability to reduce or inhibit expression of a gene or target RNA when the siRNA is present or expressed in the same cell as the target gene, e.g.","the target RNA.","siRNA-dependent post-transcriptional silencing of gene expression involves cutting the target RNA molecule at a site guided by the siRNA.","As used herein, “PCSK9” or “proprotein convertase subtilisin/kexin type 9” refers to a serine protease involved in regulating the levels of the low density lipoprotein receptor (LDLR) protein (Horton et al., 2007; Seidah and Prat, 2007).","PCSK9 has been shown to directly interact with the LDLR protein, be endocytosed along with the LDLR, and co-immunofluoresce with the LDLR throughout the endosomal pathway (Lagace et al., 2006).","PCSK9 is a prohormone-proprotein convertase in the subtilisin (S8) family of serine proteases (Seidah et al., 2003).","The sequence of PCSK9 for a variety of species is known, e.g., human PCSK9 (NCBI Gene ID No: 255738).","Nucleotide and polypeptide sequences for a number of PCSK9 isoforms are provided herein, e.g., SEQ ID NOs: 1-37.PCSK9 exists as both a pro-form and a mature form.","Autocatalysis of the PCSK9 proform occurs between Gln152 and Ser153 (VFAQ|SIP (SEQ ID NO: 67)) (Naureckiene et al., 2003), and has been shown to be required for its secretion from cells (Seidah et al., 2003).","The inactive form prior to this cleavage can be referred to herein as the “inactive”, “pro-form”, or “unprocessed” form of PCSK9.The C-terminal fragment generated by the autocatalysis event can be referred to herein as the “mature,” “cleaved”, “processed” or “active” PCSK9.Examples of pro-form and mature PCSK9 isoforms are provided herein, see, e.g.","SEQ ID NOs: 1-27.As used herein, the “catalytic domain” of PCSK9 refers to the portion of a PCSK9 polypeptide corresponding to positions 153 to 449 of PCSK9, e.g.","of SEQ ID NO: 1.As used herein, the “C-terminal domain” of PCSK9 refers to the portion of a PCSK9 polypeptide corresponding to positions 450-692 of PCSK9, e.g., of SEQ ID NO: 1.As used herein, a disease or condition “mediated by PCSK9” refers to a disease or condition which is caused by or characterized by a change in PCSK9, e.g.","a change in expression level, a change in activity, and/or the presence of a variant or mutation of PCSK9.Non-limiting examples of such diseases or conditions can include, for example, a lipid disorder, hyperlipoproteinemia, hyperlipidemia; dyslipidemia; hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication, type II diabetes, high blood pressure, and a cardiovascular disease or condition.","In an example, the disease or condition is an inflammatory or autoimmune disease or condition.","Methods of identifying and/or diagnosing such diseases and conditions are well known to medical practitioners of ordinary skill.","A subject at risk of having or developing a disease or condition mediated by PCSK9 can be a subject exhibiting one or more signs or symptoms of such a disease or condition or having one or more risk factors for such a disease or condition, e.g.","being overweight, having elevated cholesterol level, comprising one or more genetic polymorphisms known to predispose to the disease or condition, e.g., elevated cholesterol level, such as having a mutation in the LDLR (encoding low-density lipoprotein receptor) or APOB (encoding apolipoprotein B) or in the PCSK9 gene and/or having a family history of such a disease or condition.","As used herein, “ligand” refers to a molecule which can bind, e.g., specifically bind, to a second molecule or receptor.","In some embodiments, a ligand can be, e.g., an antibody, antibody fragment, antibody portion, and/or affibody.","The term “variant” as used herein refers to a peptide or nucleic acid that differs from the polypeptide or nucleic acid (eg, the most common one in humans, eg, most frequent in a database as disclosed herein, such as the 1000 Genomes Project database) by one or more amino acid or nucleic acid deletions, additions, yet retains one or more specific functions or biological activities of the naturally occurring molecule.","Amino acid substitutions include alterations in which an amino acid is replaced with a different naturally-occurring amino acid residue.","Such substitutions may be classified as “conservative”, in which case an amino acid residue contained in a polypeptide is replaced with another naturally occurring amino acid of similar character either in relation to polarity, side chain functionality or size.","Such conservative substitutions are well known in the art.","Substitutions encompassed by the present invention may also be “non-conservative”, in which an amino acid residue which is present in a peptide is substituted with an amino acid having different properties, such as naturally-occurring amino acid from a different group (e.g., substituting a charged or hydrophobic amino; acid with alanine), or alternatively, in which a naturally-occurring amino acid is substituted with a non-conventional amino acid.","In some embodiments amino acid substitutions are conservative.","Also encompassed within the term variant when used with reference to a polynucleotide or polypeptide, refers to a polynucleotide or polypeptide that can vary in primary, secondary, or tertiary structure, as compared to a reference polynucleotide or polypeptide, respectively (e.g., as compared to a wild-type polynucleotide or polypeptide).","Variants of PCSK9 are provided elsewhere herein.","Variants of PCSK9 can include the forms described herein as a, f, c, r, p, m, e h, aj, and q. Sequences of these variants are provided herein, see, e.g, SEQ ID NOs: 1-27 and in Table 1, 2 or 6.In some aspects, one can use “synthetic variants”, “recombinant variants”, or “chemically modified” polynucleotide variants or polypeptide variants isolated or generated using methods well known in the art.","“Modified variants” can include conservative or non-conservative amino acid changes, as described below.","Polynucleotide changes can result in amino acid substitutions, additions, deletions, fusions and truncations in the polypeptide encoded by the reference sequence.","Some aspects use include insertion variants, deletion variants or substituted variants with substitutions of amino acids, including insertions and substitutions of amino acids and other molecules) that do not normally occur in the peptide sequence that is the basis of the variant, for example but not limited to insertion of ornithine which do not normally occur in human proteins.","The term “conservative substitution,” when describing a polypeptide, refers to a change in the amino acid composition of the polypeptide that does not substantially alter the polypeptide's activity.","For example, a conservative substitution refers to substituting an amino acid residue for a different amino acid residue that has similar chemical properties.","Conservative amino acid substitutions include replacement of a leucine with an isoleucine or valine, an aspartate with a glutamate, or a threonine with a serine.","“Conservative amino acid substitutions” result from replacing one amino acid with another having similar structural and/or chemical properties, such as the replacement of a leucine with an isoleucine or valine, an aspartate with a glutamate, or a threonine with a serine.","Thus, a “conservative substitution” of a particular amino acid sequence refers to substitution of those amino acids that are not critical for polypeptide activity or substitution of amino acids with other amino acids having similar properties (e.g., acidic, basic, positively or negatively charged, polar or non-polar, etc.)","such that the substitution of even critical amino acids does not reduce the activity of the peptide, (i.e.","the ability of the peptide to penetrate the blood brain barrier (BBB)).","Conservative substitution tables providing functionally similar amino acids are well known in the art.","For example, the following six groups each contain amino acids that are conservative substitutions for one another: 1) Alanine (A), Serine (S), Threonine (T); 2) Aspartic acid (D), Glutamic acid (E); 3) Asparagine (N), Glutamine (Q); 4) Arginine (R), Lysine (K); 5) Isoleucine (I), Leucine (L), Methionine (M), Valine (V); and 6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W).","(See also Creighton, Proteins, W. H. Freeman and Company (1984), incorporated by reference in its entirety.)","In some embodiments, individual substitutions, deletions or additions that alter, add or delete a single amino acid or a small percentage of amino acids can also be considered “conservative substitutions” if the change does not reduce the activity of the peptide.","Insertions or deletions are typically in the range of about 1 to 5 amino acids.","The choice of conservative amino acids may be selected based on the location of the amino acid to be substituted in the peptide, for example if the amino acid is on the exterior of the peptide and expose to solvents, or on the interior and not exposed to solvents.","In alternative embodiments, one can select the amino acid which will substitute an existing amino acid based on the location of the existing amino acid, i.e.","its exposure to solvents (i.e.","if the amino acid is exposed to solvents or is present on the outer surface of the peptide or polypeptide as compared to internally localized amino acids not exposed to solvents).","Selection of such conservative amino acid substitutions are well known in the art, for example as disclosed in Dordo et al, J. Mol Biol, 1999, 217, 721-739 and Taylor et al, J. Theor.","Biol.","119(1986); 205-218 and S. French and B. Robson, J. Mol.","Evol.","19(1983)171.Accordingly, one can select conservative amino acid substitutions suitable for amino acids on the exterior of a protein or peptide (i.e.","amino acids exposed to a solvent), for example, but not limited to, the following substitutions can be used: substitution of Y with F, T with S or K, P with A, E with D or Q, N with D or G, R with K, G with N or A, T with S or K, D with N or E, I with L or V, F with Y, S with T or A, R with K, G with N or A, K with R, A with S, K or P. In alternative embodiments, one can also select conservative amino acid substitutions encompassed suitable for amino acids on the interior of a protein or peptide, for example one can use suitable conservative substitutions for amino acids is on the interior of a protein or peptide (i.e.","the amino acids are not exposed to a solvent), for example but not limited to, one can use the following conservative substitutions: where Y is substituted with F, T with A or S, I with L or V, W with Y, M with L, N with D, G with A, T with A or S, D with N, I with L or V, F with Y or L, S with A or T and A with S, G, T or V. In some embodiments, non-conservative amino acid substitutions are also encompassed within the term of variants.","As used herein an “antibody” refers to IgG, IgM, IgA, IgD or IgE molecules or antigen-specific antibody fragments thereof (including, but not limited to, a Fab, F(ab′)2, Fv, disulphide linked Fv, scFv, single domain antibody, closed conformation multispecific antibody, disulphide-linked scfv, diabody), whether derived from any species that naturally produces an antibody, or created by recombinant DNA technology; whether isolated from serum, B-cells, hybridomas, transfectomas, yeast or bacteria.","Antibodies can be humanized using routine technology.","As described herein, an “antigen” is a molecule that is bound by a binding site on an antibody agent.","Typically, antigens are bound by antibody ligands and are capable of raising an antibody response in vivo.","An antigen can be a polypeptide, protein, nucleic acid or other molecule or portion thereof.","The term “antigenic determinant” refers to an epitope on the antigen recognized by an antigen-binding molecule, and more particularly, by the antigen-binding site of said molecule.","As used herein, the term “antibody fragment” refers to a polypeptide that includes at least one immunoglobulin variable domain or immunoglobulin variable domain sequence and which specifically binds a given antigen.","An antibody fragment can comprise an antibody or a polypeptide comprising an antigen-binding domain of an antibody.","In some embodiments, an antibody fragment can comprise a monoclonal antibody or a polypeptide comprising an antigen-binding domain of a monoclonal antibody.","For example, an antibody can include a heavy (H) chain variable region (abbreviated herein as VH), and a light (L) chain variable region (abbreviated herein as VL).","In another example, an antibody includes two heavy (H) chain variable regions and two light (L) chain variable regions.","The term “antibody fragment” encompasses antigen-binding fragments of antibodies (e.g., single chain antibodies, Fab and sFab fragments, F(ab′)2, Fd fragments, Fv fragments, scFv, and domain antibodies (dAb) fragments (see, e.g.","de Wildt et al., Eur J. Immunol.","1996; 26(3):629-39; which is incorporated by reference herein in its entirety)) as well as complete antibodies.","An antibody can have the structural features of IgA, IgG, IgE, IgD, IgM (as well as subtypes and combinations thereof).","Antibodies can be from any source, including mouse, rabbit, pig, rat, and primate (human and non-human primate) and primatized antibodies.","Antibodies also include midibodies, humanized antibodies, chimeric antibodies, and the like.","As used herein, “antibody variable domain” refers to the portions of the light and heavy chains of antibody molecules that include amino acid sequences of Complementarity Determining Regions (CDRs; ie., CDR1, CDR2, and CDR3), and Framework Regions (FRs).","VH refers to the variable domain of the heavy chain.","VL refers to the variable domain of the light chain.","According to the methods used in this invention, the amino acid positions assigned to CDRs and FRs may be defined according to Kabat (Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, Md., 1987 and 1991)) or according to IMGT nomenclature.","D domain or region refers to the diversity domain or region of an antibody chain.","J domain or region refers to the joining domain or region of an antibody chain.","An antibody “gene segment”, e.g.","a VH gene segment, D gene segment, or JH gene segment refers to oligonucleotide having a nucleic acid sequence that encodes that portion of an antibody, e.g.","a VH gene segment is an oligonucleotide comprising a nucleic acid sequence that encodes a polypeptide VH domain.","The VH and VL regions can be further subdivided into regions of hypervariability, termed “complementarity determining regions” (“CDR”), interspersed with regions that are more conserved, termed “framework regions” (“FR”).","The extent of the framework region and CDRs has been precisely defined (see, IMGT or Kabat, E. A., et al.","(1991) Sequences of Proteins of Immunological Interest, Fifth Edition, U.S. Department of Health and Human Services, NIH Publication No.","91-3242, and Chothia, C. et al.","(1987) J. Mol.","Biol.","196:901-917; which are incorporated by reference herein in their entireties).","Each VH and VL is typically composed of three CDRs and four FRs, arranged from amino-terminus to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4.The terms “antigen-binding fragment” or “antigen-binding domain”, which are used interchangeably herein are used to refer to one or more fragments of a full length antibody that retain the ability to specifically bind to a target of interest.","Examples of binding fragments encompassed within the term “antigen-binding fragment” of a full length antibody include (i) a Fab fragment, a monovalent fragment consisting of the VL, VH, CL and CH1 domains; (ii) a F(ab′)2 fragment, a bivalent fragment including two Fab fragments linked by a disulfide bridge at the hinge region; (iii) an Fd fragment consisting of the VH and CH1 domains; (iv) an Fv fragment consisting of the VL and VH domains of a single arm of an antibody, (v) a dAb fragment (Ward et al., (1989) Nature 341:544-546; which is incorporated by reference herein in its entirety), which consists of a VH or VL domain; and (vi) an isolated complementarity determining region (CDR) that retains specific antigen-binding functionality.","As used herein, the term “antibody binding site” refers to a polypeptide or domain that comprises one or more CDRs of an antibody and is capable of binding an antigen.","For example, the polypeptide comprises a CDR3 (eg, HCDR3).","For example the polypeptide comprises CDRs 1 and 2 (eg, HCDR1 and 2) or CDRs 1-3 of a variable domain of an antibody (eg, HCDRs1-3).","In an example, the antibody binding site is provided by a single variable domain (eg, a VH or VL domain).","In another example, the binding site comprises a VH/VL pair or two or more of such pairs.","As used herein, the term “specific binding” refers to a chemical interaction between two molecules, compounds, cells and/or particles wherein the first entity binds to the second, target entity with greater specificity and affinity than it binds to a third entity which is a non-target.","For example, in an diagnostic test the specific binding of a ligand can distinguish between two variant PCSK9 proteins as described herein.","In some embodiments, specific binding can refer to an affinity of the first entity for the second target entity which is at least 10 times, at least 50 times, at least 100 times, at least 500 times, at least 1000 times or greater than the affinity for the third nontarget entity.","In the context of oligonucleotide strands which interact via hybridization, specific binding can be “specific hybridization.” Additionally, and as described herein, a recombinant human(ized) antibody can be further optimized to decrease potential immunogenicity, while maintaining functional activity, for therapy in humans.","In this regard, functional activity means a polypeptide capable of displaying one or more known functional activities associated with a recombinant antibody or antibody reagent thereof as described herein.","Such functional activities include, e.g.","the ability to bind to a target molecule.","The term “immunizing” refers to the step or steps of administering one or more antigens to an animal so that antibodies can be raised in the animal Generally, immunizing comprises injecting the antigen or antigens into the animal.","Immunization can involve one or more administrations of the antigen or antigens.","Suitable methods are prime-boost and RIMMS procedures as known to the skilled person in the art.","As used herein, an “affibody” refers to a relatively small synthetic protein molecule that has high binding affinity for a target protein (e.g.","for PCSK9 or a variant therefo).","Affibodies are composed of a three-helix bundle domain derived from the IgG-binding domain of staphylococcal protein A.","The protein domain consists of a 58 amino acid sequence, with 13 randomized amino acids affording a range of affibody variants.","Despite being significantly smaller than an antibody (an affibody weighs about 6 kDa while an antibody commonly weighs about 150 kDa), an affibody molecule works like an antibody since its binding site is approximately equivalent in surface area to the binding site of an antibody.","As used herein, “VH3-23*04” refers to a human VH domain variant comprising the polypeptide sequence of SEQ ID NO: 38.As opposed to the reference sequence, VH3-23*04 has a valine residue instead of a leucine residue (see FIGS.","3 and 4; L24V, numbering including signal sequence; valine at position 5 shown in FIG.","4) as a result of the presence of the rs56069819 SNP in the nucleic acid sequence encoding the VH domain.","As used herein, “rs56069819” refers to a mutation or variant in a VH gene segment from adenosine to cytosine (or thymine to guanine, depending upon the strand of DNA which is being read), resulting in the VH domain encoding VH3-23*04.Rs56069819 is depicted in FIG.","4 and SEQ ID NO: 39, which demonstrate the T->G mutation (it is noted that the dbSNP entry for RS5606819 depicts the other strand, which comprises the A->C mutation).","Further description of VH3-23*04 can be found, e.g., in US Patent Publication 2013/0071405; which is incorporated by reference herein in its entirety.","As used herein, “determine” or “determining” refers to ascertaining, e.g., by a quantitative or qualitative analysis.","As used herein, “has been determined” can refer to ascertaining on the basis of previously obtained information or simultaneously obtained information.","In some aspects of all embodiments of the invention selecting can include automation such as a computer implemented software program that upon input of the relevant data such as ethnicity or a panel of SNP data can make the determination based on the instructions set forth herein.","As used herein, “assaying” refers to assessing, evaluating, quantifying, measuring, or characterizing an analyte, e.g., measuring the level of an analyte in a sample, identifying an analyte, or detecting the presence or absence of an analyte in a sample.","In some embodiments, assaying refers to detecting a presence or absence of the analyte of interest.","In some embodiments, assaying refers to quantifying an amount of an analyte, e.g., providing a measure of concentration or degree of analyte abundance.","In some embodiments, assaying refers to enumerating the number of molecules of analyte present in a sample and/or specimen, e.g., to determine an analyte copy number.","As used herein “multiplex” refers to the carrying out of a method or process simultaneously and in the same reaction vessel on two or more, typically three or more, different target sequences, e.g.","on two or more isoforms of PCSK9, or PCSK9 and an additional target.","A multiplex analysis typically includes analysis of 10-50: 10-100; 10-1000, 10-5000, 10-10000 reactions in a multiplex format, such as a multiwall, an array, or a multichannel reaction.","Often the analysis or multiplex analysis is also automated using robotics and typically software executed by a computer and may include a robotic handling of samples, automatic or robotic selection of positive or negative results, assaying for presence of absence of a target, such as a nucleic acid polymorphism or a protein variant.","The term “biological sample” or “test sample” as used herein denotes a sample taken or isolated from a biological organism, e.g., a sample from a subject.","Exemplary biological samples include, but are not limited to, a biofluid sample; serum; plasma; urine; saliva; hair, epithelial cells, skin, a tumor biopsy and/or tissue sample etc.","The term also includes a mixture of the above-mentioned samples.","The term “test sample” or “biological sample” also includes untreated or pretreated (or pre-processed) biological samples.","For the analysis of nucleic acids, the biological sample should typically comprise at least one cell comprising nucleic acids.","The test sample can be obtained by removing a sample of cells from a subject, but can also be accomplished by using previously isolated cells (e.g.","isolated at a prior time point and isolated by the same or another person).","In addition, the test sample can be freshly collected or a previously collected, refrigerated, frozen or otherwise preserved sample.","In some embodiments, the test sample can be an untreated test sample.","As used herein, the phrase “untreated test sample” refers to a test sample that has not had any prior sample pre-treatment except for dilution and/or suspension in a solution.","Exemplary methods for treating a test sample include, but are not limited to, centrifugation, filtration, sonication, homogenization, heating, freezing and thawing, and combinations thereof.","In some embodiments, the test sample can be a frozen test sample, e.g., a frozen tissue.","The frozen sample can be thawed before employing methods, assays and systems described herein.","After thawing, a frozen sample can be centrifuged before being subjected to methods, assays and systems described herein.","In some embodiments, the test sample is a clarified test sample, for example, by centrifugation and collection of a supernatant comprising the clarified test sample.","In some embodiments, a test sample can be a pre-processed test sample, for example, supernatant or filtrate resulting from a treatment selected from the group consisting of centrifugation, filtration, thawing, purification, and any combinations thereof.","In some embodiments, the test sample can be treated with a chemical and/or biological reagent.","Chemical and/or biological reagents can be employed to protect and/or maintain the stability of the sample, including biomolecules (e.g., nucleic acid and protein) therein, during processing.","One exemplary reagent is a protease inhibitor, which is generally used to protect or maintain the stability of protein during processing.","The skilled artisan is well aware of methods and processes appropriate for pre-processing of biological samples required for determination of the level of an expression product as described herein.","As used herein, “genotyping” refers to a process of determining the specific allelic composition of a cell and/or subject at one or more position within the genome, e.g.","by determining the nucleic acid sequence at that position.","Genotyping refers to a nucleic acid analysis and/or analysis at the nucleic acid level.","As used herein, “phenotyping” refers a process of determining the identity and/or composition of an expression product of a cell and/or subject, e.g.","by determining the polypeptide sequence of an expression product.","Phenotyping refers to a protein analysis and/or analysis at the protein level.","As used herein, the term “nucleic acid amplification” refers to the production of additional copies of a nucleic acid sequence and is typically carried out using polymerase chain reaction (PCR) or ligase chain reaction (LCR) technologies well known in the art (Dieffenbach, C. W. and G. S. Dveksler (1995) PCR Primer, a Laboratory Manual, Cold Spring Harbor Press, Plainview, N.Y.).","Other methods for amplification are also contemplated in aspects of the invention.","The term “allele-specific amplification” refers to a reaction (e.g., PCR reaction) in which at least one of the primers (e.g., allele-specific primer) is chosen from a polymorphic area of gene (e.g., single nucleotide polymorphism), with the polymorphism located at or near the primer's 3′-end.","A mismatched primer will not initiate amplification, whereas a matched primer will initiate amplification.","The appearance of an amplification product is indicative of the presence of the polymorphism.","As used herein, “sequencing” refers to the determination of the exact order of nucleotide bases in a strand of DNA (deoxyribonucleic acid) or RNA (ribonucleic acid) or the exact order of amino acids residues or peptides in a protein.","Nucleic acid sequencing can be done using Sanger sequencing or next-generation high-throughput sequencing.","As used herein “next-generation sequencing” refers to oligonucleotide sequencing technologies that have the capacity to sequence oligonucleotides at speeds above those possible with conventional sequencing methods (e.g.","Sanger sequencing), due to performing and reading out thousands to millions of sequencing reactions in parallel.","Non-limiting examples of next-generation sequencing methods/platforms include Massively Parallel Signature Sequencing (Lynx Therapeutics); 454 pyro-sequencing (454 Life Sciences/Roche Diagnostics); solid-phase, reversible dye-terminator sequencing (Solexa/Illumina): SOLiD technology (Applied Biosystems); Ion semiconductor sequencing (ION Torrent); DNA nanoball sequencing (Complete Genomics); and technologies available from Pacific Biosciences, Intelligen Bio-systems, Oxford Nanopore Technologies, and Helicos Biosciences.","Next-generation sequencing technologies and the constraints and design parameters of associated sequencing primers are well known in the art (see, e.g.","Shendure, et al., “Next-generation DNA sequencing,” Nature, 2008, vol.","26, No.","10, 1135-1145; Mardis, “The impact of next-generation sequencing technology on genetics,” Trends in Genetics, 2007, vol.","24, No.","3, pp.","133-141; Su, et al., “Next-generation sequencing and its applications in molecular diagnostics” Expert Rev Mol Diagn, 2011, 11(3):333-43; Zhang et al., “The impact of next-generation sequencing on genomics”, J Genet Genomics, 2011, 38(3):95-109; (Nyren, P. et al.","Anal Biochem 208: 17175 (1993); Bentley, D. R. Curr Opin Genet Dev 16:545-52 (2006); Strausberg, R. L., et al.","Drug Disc Today 13:569-77 (2008); U.S. Pat.","No.","7,282,337; U.S. Pat.","No.","7,279,563; U.S. Pat.","No.","7,226,720; U.S. Pat.","No.","7,220,549; U.S. Pat.","No.","7,169,560; U.S. Pat.","No.","6,818,395; U.S. Pat.","No.","6,911,345; US Pub.","Nos.","2006/0252077; 2007/0070349; and 20070070349; which are incorporated by reference herein in their entireties).","As used herein, “nucleic acid hybridization” refers to the pairing of complementary RNA and DNA strands as well as the pairing of complementary DNA single strands.","In some embodiments, nucleic acid hybridization can refer to a method of determining a nucleic acid sequence and/or identity by hybridizing a nucleic acid sample with a probe, e.g.","Northern or Southern blot analysis or microarray analysis.","As used herein, the terms “treat,” “treatment,” “treating,” or “amelioration” refer to therapeutic treatments, wherein the object is to reverse, alleviate, ameliorate, inhibit, slow down or stop the progression or severity of a condition associated with a disease or disorder.","The term “treating” includes reducing or alleviating at least one adverse effect or symptom of a condition, disease or disorder.","Treatment is generally “effective” if one or more symptoms or clinical markers are reduced.","Alternatively, treatment is “effective” if the progression of a disease is reduced or halted.","That is, “treatment” includes not just the improvement of symptoms or markers, but also a cessation of, or at least slowing of, progress or worsening of symptoms compared to what would be expected in the absence of treatment.","Beneficial or desired clinical results include, but are not limited to, alleviation of one or more symptom(s), diminishment of extent of disease, stabilized (i.e., not worsening) state of disease, delay or slowing of disease progression, amelioration or palliation of the disease state, remission (whether partial or total), and/or decreased mortality, whether detectable or undetectable.","The term “treatment” of a disease also includes providing relief from the symptoms or side-effects of the disease (including palliative treatment).","For treatment to be effective a complete cure is not contemplated.","The method can in certain aspects include cure as well.","As used herein, the term “pharmaceutical composition” refers to the active agent in combination with a pharmaceutically acceptable carrier e.g.","a carrier commonly used in the pharmaceutical industry.","The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio.","As used herein, the term “administering,” refers to the placement of a compound as disclosed herein into a subject by a method or route which results in at least partial delivery of the agent at a desired site.","Pharmaceutical compositions comprising the compounds disclosed herein can be administered by any appropriate route which results in an effective treatment in the subject.","Multiple compositions can be administered separately or simultaneously.","Separate administration refers to the two compositions being administered at different times, e.g.","at least 10, 20, 30, or 10-60 minutes apart, or 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 hours apart.","One can also administer compositions at 24 hours apart, or even longer apart.","Alternatively, two or more compositions can be administered simultaneously, e.g.","less than 10 or less than 5 minutes apart.","Compositions administered simultaneously can, in some aspects, be administered as a mixture, with or without similar or different time release mechanism for each of the components.","As used herein, “contacting” refers to any suitable means for delivering, or exposing, an agent to at least one complex, enzyme, or cell.","Exemplary delivery methods include, but are not limited to, direct delivery to cell culture medium, perfusion, injection, or other delivery method well known to one skilled in the art.","As used herein, “obtain” refers to any method of acquiring, securing, procuring, or coming into the possession of, e.g.","a sample.","Obtaining a biological sample from a subject can comprise physical removing a sample from a subject (e.g.","drawing blood or taking a hair or saliva sample) without or without active participation from the subject; receiving a sample from a subject (e.g.","the subject collects a saliva or hair sample themselves and provides it, e.g.","in a container provided for the purpose); or procuring a sample from a storage facility, medical facility, or medical provider.","Obtain from the human or subject, refers to an active step of, e.g., drawing blood or taking a tissue or cell sample.","As used herein, “cholesterol level” refers to a level of one or more of total cholesterol, LDL cholesterol, HDL cholesterol, and/or triglycerides.","Cholesterol levels can be the level of cholesterol in the blood of a subject.","As used herein in reference to cholesterol levels, “maintain” refers to preventing the level from worsening (e.g.","increasing).","In some embodiments, maintaining a particular level refers to a process that results in the cholesterol level not increasing by more than 10% over time.","Maintaining may also refer to maintaining a previously achieved level.","For example, if a human has received statin treatment, one can maintain the cholesterol level achieved using the statin treatment.","In some embodiments, the subject treated according to the methods described herein has previously had their cholesterol level reduced.","As used herein, “previously reduced” indicates that at a prior point in time, the subject experienced a decrease in cholesterol levels.","The decrease can be due to administration of a pharmaceutical composition (e.g.","administration of a composition as described herein or another composition, e.g.","a statin) or due to another cause, e.g.","a change in diet and/or exercise.","An existing treatment for high cholesterol levels is the administration of a statin.","As referred to herein, a “statin” (also known as HMG-CoA reductase inhibitors) are inhibitors of the enzyme HMG-coA reductase, which mediates cholesterol production in the liver.","Statins, by competitively binding HMG-CoA reductase, prevent the binding of HMG-CoA to the enzyme and thereby inhibit the activity of the reductase (e.g.","the production of mevalonate).","Non-limiting examples of statins can include atorvastatin (LIPITOR™), fluvastatin (LESCOL™), lovastatin (MEVACOR™, ALTOCOR™), pitavastatin (LIVALO™), pravastatin (PRAVACHOL™), rosuvastatin (CRESTOR™), and simvastatin (ZOCOR™).","Statins can be administered in combination with other agents, e.g.","the combination of ezetimibe and simvastatin.","Some subjects are, or become, resistant to statin treatment.","As used herein, “resistant to statin treatment” or “reduced responsiveness to statin treatment” refers to a subject exhibiting a statistically significantly lower response to the administration of a statin as compared to a reference level.","The reference level can be, e.g., the average response for a population of subjects or the level of the individual subject at an earlier date.","A response to statin treatment is readily measured by one of skill in the art, e.g., measurement of cholesterol levels, changes in cholesterol levels, and/or HMG-CoA reductase activity.","As used herein, the term “detectable label” refers to a molecule or moiety that can be detected, e.g.","measured and/or determined to be present or absent.","Detectable labels can comprise, for example, a light-absorbing dye, a fluorescent dye, or a radioactive label.","Detectable labels, methods of detecting them, and methods of incorporating them into reagents (e.g.","antibodies and nucleic acid probes) are well known in the art.","In some embodiments, detectable labels can include labels that can be detected by spectroscopic, photochemical, biochemical, immunochemical, electromagnetic, radiochemical, or chemical means, such as fluorescence, chemifluoresence, or chemiluminescence, or any other appropriate means.","The detectable labels used in the methods described herein can be primary labels (where the label comprises a moiety that is directly detectable or that produces a directly detectable moiety) or secondary labels (where the detectable label binds to another moiety to produce a detectable signal, e.g., as is common in immunological labeling using secondary and tertiary antibodies).","The detectable label can be linked by covalent or non-covalent means to the reagent.","Alternatively, a detectable label can be linked such as by directly labeling a molecule that achieves binding to the reagent via a ligand-receptor binding pair arrangement or other such specific recognition molecules.","Detectable labels can include, but are not limited to radioisotopes, bioluminescent compounds, chromophores, antibodies, chemiluminescent compounds, fluorescent compounds, metal chelates, and enzymes.","In other embodiments, the detectable label can be a fluorescent compound.","When the fluorescently label is exposed to light of the proper wavelength, its presence can then be detected due to fluorescence.","In some embodiments, a detectable label can be a fluorescent dye molecule, or fluorophore including, but not limited to fluorescein, phycoerythrin, phycocyanin, o-phthaldehyde, fluorescamine, Cy3™, Cy5™, allophycocyanine, Texas Red, peridenin chlorophyll, cyanine, tandem conjugates such as phycoerythrin-Cy5™, green fluorescent protein, rhodamine, fluorescein isothiocyanate (FITC) and Oregon Green™, rhodamine and derivatives (e.g., Texas red and tetrarhodimine isothiocynate (TRITC)), biotin, phycoerythrin, AMCA, CyDyes™, 6-carboxyfhiorescein (commonly known by the abbreviations FAM and F), 6-carboxy-2′,4′,7′,4,7-hexachlorofiuorescein (HEX), 6-carboxy-4′,5′-dichloro-2′,7′-dimethoxyfiuorescein (JOE or J), N,N,N′,N′-tetramethyl-6carboxyrhodamine (TAMRA or T), 6-carboxy-X-rhodamine (ROX or R), 5-carboxyrhodamine-6G (R6G5 or G5), 6-carboxyrhodamine-6G (R6G6 or G6), and rhodamine 110; cyanine dyes, e.g.","Cy3, Cy5 and Cy7 dyes; coumarins, e.g umbelliferone; benzimide dyes, e.g.","Hoechst 33258; phenanthridine dyes, e.g.","Texas Red; ethidium dyes; acridine dyes; carbazole dyes; phenoxazine dyes; porphyrin dyes; polymethine dyes, e.g.","cyanine dyes such as Cy3, Cy5, etc; BODIPY dyes and quinoline dyes.","In some embodiments, a detectable label can be a radiolabel including, but not limited to 3H, 125I, 35S, 14C, 32P, and 33P.","In some embodiments, a detectable label can be an enzyme including, but not limited to horseradish peroxidase and alkaline phosphatase.","An enzymatic label can produce, for example, a chemiluminescent signal, a color signal, or a fluorescent signal.","Enzymes contemplated for use as a detectable label can include, but are not limited to, malate dehydrogenase, staphylococcal nuclease, delta-V-steroid isomerase, yeast alcohol dehydrogenase, alpha-glycerophosphate dehydrogenase, triose phosphate isomerase, horseradish peroxidase, alkaline phosphatase, asparaginase, glucose oxidase, beta-galactosidase, ribonuclease, urease, catalase, glucose-VI-phosphate dehydrogenase, glucoamylase and acetylcholinesterase.","In some embodiments, a detectable label is a chemiluminescent label, including, but not limited to lucigenin, luminol, luciferin, isoluminol, theromatic acridinium ester, imidazole, acridinium salt and oxalate ester.","In some embodiments, a detectable label can be a spectral colorimetric label including, but not limited to colloidal gold or colored glass or plastic (e.g., polystyrene, polypropylene, and latex) beads.","In some embodiments, reagents can also be labeled with a detectable tag, such as c-Myc, HA, VSV-G, HSV, FLAG, V5, HIS, or biotin.","Other detection systems can also be used, for example, a biotin-streptavidin system.","In this system, the antibodies immunoreactive (i. e. specific for) with the biomarker of interest is biotinylated.","Quantity of biotinylated antibody bound to the biomarker is determined using a streptavidin-peroxidase conjugate and a chromagenic substrate.","Such streptavidin peroxidase detection kits are commercially available, e. g. from DAKO; Carpinteria, Calif. A reagent can also be detectably labeled using fluorescence emitting metals such as 152Eu, or others of the lanthanide series.","These metals can be attached to the reagent using such metal chelating groups as diethylenetriaminepentaacetic acid (DTPA) or ethylenediaminetetraacetic acid (EDTA).","As used herein, “authorization number” or “marketing authorization number” refers to a number issued by a regulatory agency upon that agency determining that a particular medical product and/or composition may be marketed and/or offered for sale in the area under the agency's jurisdiction.","As used herein “regulatory agency” refers to one of the agencies responsible for evaluating, e.g, the safety and efficacy of a medical product and/or composition and controlling the sales/marketing of such products and/or compositions in a given area.","The Food and Drug Administration (FDA) in the US and the European Medicines Agency (EPA) in Europe are but two examples of such regulatory agencies.","Other non-limiting examples can include SDA, MPA, MHPRA, IMA, ANMAT, Hong Kong Department of Health-Drug Office, CDSCO, Medsafe, and KFDA.","As used herein, “injection device” refers to a device that is designed for carrying out injections, an injection including the steps of temporarily fluidically coupling the injection device to a person's tissue, typically the subcutaneous tissue.","An injection further includes administering an amount of liquid drug into the tissue and decoupling or removing the injection device from the tissue.","In some embodiments, an injection device can be an intravenous device or IV device, which is a type of injection device used when the target tissue is the blood within the circulatory system, e.g., the blood in a vein.","A common, but non-limiting example of an injection device is a needle and syringe.","As used herein, a “buffer” refers to a chemical agent that is able to absorb a certain quantity of acid or base without undergoing a strong variation in pH.","As used herein, “packaging” refers to how the components are organized and/or restrained into a unit fit for distribution and/or use.","Packaging can include, e.g., boxes, bags, syringes, ampoules, vials, tubes, clamshell packaging, barriers and/or containers to maintain sterility, labeling, etc.","As used herein, “instructions” refers to a display of written, printed or graphic matter on the immediate container of an article, for example the written material displayed on a vial containing a pharmaceutically active agent, or details on the composition and use of a product of interest included in a kit containing a composition of interest.","Instructions set forth the method of the treatment as contemplated to be administered or performed.","As used herein, a “solid surface” refers to an object suitable for the attachment of biomolecules.","Non-limiting examples of a solid surface can include a particle (including, but not limited to an agarose or latex bead or particle or a magnetic particle), a bead, a nanoparticle, a polymer, a substrate, a slide, a coverslip, a plate, a dish, a well, a membrane, and/or a grating.","The solid surface can include many different materials including, but not limited to, polymers, plastics, resins, polysaccharides, silicon or silica based materials, carbon, metals, inorganic glasses, and membranes.","As used herein, “classification” of a subject, e.g., classification of the subject's ancestry refers to determining if the subject has biological ancestors who originated in a particular geographical area, and are therefore likely to have particular genetic variants found in the populations which have historically occupied that area.","Classification can comprise, e.g.","obtaining information on the subject's family, interviewing the subject or a family member regarding their biological family's ancestry, and/or genetic testing.","Classification can be on the basis used for the 1000 Genomes Project, as will be familiar to the skilled person in the art.","In some embodiments, the subject can be classified as being of a particular ancestry if at least the subject's genome comprises a substantial number of different alleles in common with other humans of that ancestry (eg, determined by reference to the 1000 Genomes Project database), for example, at least 10, 20, 30, 40, 50 or 100 or more alleles in common.","Abbreviations for particular ancestral groups are provided in Table 4.The term “statistically significant” or “significantly” refers to statistical significance and generally means a two standard deviation (2SD) or greater difference.","Other than in the operating examples, or where otherwise indicated, all numbers expressing quantities of ingredients or reaction conditions used herein should be understood as modified in all instances by the term “about.” The term “about” when used in connection with percentages can mean±1%.","As used herein the term “comprising” or “comprises” is used in reference to compositions, methods, and respective component(s) thereof, that are essential to the method or composition, yet open to the inclusion of unspecified elements, whether essential or not.","The term “consisting of” refers to compositions, methods, and respective components thereof as described herein, which are exclusive of any element not recited in that description of the embodiment.","As used herein the term “consisting essentially of” refers to those elements required for a given embodiment.","The term permits the presence of elements that do not materially affect the basic and novel or functional characteristic(s) of that embodiment.","The singular terms “a,” “an,” and “the” include plural referents unless context clearly indicates otherwise.","Similarly, the word “or” is intended to include “and” unless the context clearly indicates otherwise.","Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of this disclosure, suitable methods and materials are described below.","The abbreviation, “e.g.” is derived from the Latin exempli gratia, and is used herein to indicate a non-limiting example.","Thus, the abbreviation “e.g.” is synonymous with the term “for example.” Definitions of common terms in cell biology and molecular biology can be found in “The Merck Manual of Diagnosis and Therapy”, 19th Edition, published by Merck Research Laboratories, 2006 (ISBN 0-911910-19-0); Robert S. Porter et al.","(eds.","), The Encyclopedia of Molecular Biology, published by Blackwell Science Ltd., 1994 (ISBN 0-632-02182-9); Benjamin Lewin, Genes X, published by Jones & Bartlett Publishing, 2009 (ISBN-10: 0763766321); Kendrew et al.","(eds.","), Molecular Biology and Biotechnology: a Comprehensive Desk Reference, published by VCH Publishers, Inc., 1995 (ISBN 1-56081-569-8) and Current Protocols in Protein Sciences 2009, Wiley Intersciences, Coligan et al., eds.","Unless otherwise stated, the present invention was performed using standard procedures, as described, for example in Sambrook et al., Molecular Cloning: A Laboratory Manual (4 ed.","), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., USA (2012); Davis et al., Basic Methods in Molecular Biology, Elsevier Science Publishing, Inc., New York, USA (1995); or Methods in Enzymology: Guide to Molecular Cloning Techniques Vol.","152, S. L. Berger and A. R. Kimmel Eds., Academic Press Inc., San Diego, USA (1987); Current Protocols in Protein Science (CPPS) (John E. Coligan, et.","al., ed., John Wiley and Sons, Inc.), Current Protocols in Cell Biology (CPCB) (Juan S. Bonifacino et. al.","ed., John Wiley and Sons, Inc.), and Culture of Animal Cells: A Manual of Basic Technique by R. Ian Freshney, Publisher: Wiley-Liss; 5th edition (2005), Animal Cell Culture Methods (Methods in Cell Biology, Vol.","57, Jennie P. Mather and David Barnes editors, Academic Press, 1st edition, 1998) which are all incorporated by reference herein in their entireties.","Other terms are defined herein within the description of the various aspects of the invention.","All patents and other publications; including literature references, issued patents, published patent applications, and co-pending patent applications; cited throughout this application are expressly incorporated herein by reference for the purpose of describing and disclosing, for example, the methodologies described in such publications that might be used in connection with the technology described herein.","These publications are provided solely for their disclosure prior to the filing date of the present application.","Nothing in this regard should be construed as an admission that the inventors are not entitled to antedate such disclosure by virtue of prior invention or for any other reason.","All statements as to the date or representation as to the contents of these documents is based on the information available to the applicants and does not constitute any admission as to the correctness of the dates or contents of these documents.","The description of embodiments of the disclosure is not intended to be exhaustive or to limit the disclosure to the precise form disclosed.","While specific embodiments of, and examples for, the disclosure are described herein for illustrative purposes, various equivalent modifications are possible within the scope of the disclosure, as those skilled in the relevant art will recognize.","For example, while method steps or functions are presented in a given order, alternative embodiments may perform functions in a different order, or functions may be performed substantially concurrently.","The teachings of the disclosure provided herein can be applied to other procedures or methods as appropriate.","The various embodiments described herein can be combined to provide further embodiments.","Aspects of the disclosure can be modified, if necessary, to employ the compositions, functions and concepts of the above references and application to provide yet further embodiments of the disclosure.","Moreover, due to biological functional equivalency considerations, some changes can be made in protein structure without affecting the biological or chemical action in kind or amount.","These and other changes can be made to the disclosure in light of the detailed description.","All such modifications are intended to be included within the scope of the appended claims.","Specific elements of any of the foregoing embodiments can be combined or substituted for elements in other embodiments.","Furthermore, while advantages associated with certain embodiments of the disclosure have been described in the context of these embodiments, other embodiments may also exhibit such advantages, and not all embodiments need necessarily exhibit such advantages to fall within the scope of the disclosure.","It will be understood that particular configurations, aspects, examples, clauses and embodiments described herein are shown by way of illustration and not as limitations of the invention.","The principal features of this invention can be employed in various embodiments without departing from the scope of the invention.","Those skilled in the art will recognize, or be able to ascertain using no more than routine study, numerous equivalents to the specific procedures described herein.","Such equivalents are considered to be within the scope of this invention and are covered by the claims.","All publications and patent applications mentioned in the specification are indicative of the level of skill of those skilled in the art to which this invention pertains.","All publications and patent applications are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.","The use of the word “a” or “an” when used in conjunction with the term “comprising” in the claims and/or the specification may mean “one,” but it is also consistent with the meaning of “one or more,” “at least one,” and “one or more than one.” The use of the term “or” in the claims is used to mean “and/or” unless explicitly indicated to refer to alternatives only or the alternatives are mutually exclusive, although the disclosure supports a definition that refers to only alternatives and “and/or.” Throughout this application, the term “about” is used to indicate that a value includes the inherent variation of error for the device, the method being employed to determine the value, or the variation that exists among the study subjects.","As used in this specification and claim(s), the words “comprising” (and any form of comprising, such as “comprise” and “comprises”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “includes” and “include”) or “containing” (and any form of containing, such as “contains” and “contain”) are inclusive or open-ended and do not exclude additional, unrecited elements or method steps Any part of this disclosure may be read in combination with any other part of the disclosure, unless otherwise apparent from the context.","All of the compositions and/or methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure.","While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the compositions and/or methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the invention.","All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims.","The present invention is described in more detail in the following non limiting Examples.","Some embodiments of the technology described herein can be defined according to any of the following numbered paragraphs: 1.A method of treating or preventing a disease or condition in a human, wherein the disease or condition is mediated by a Target of Interest (TOI), wherein the TOI is present in humans as different polymorphic variants, the method comprising a. selecting a human that is positive for the TOI polymorphic variant, wherein the TOI in said human is encoded by a nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and/or wherein the TOI in said human is encoded by a nucleotide sequence comprising an allele having total human genotype frequency of less than 50%; and b. administering to the human an anti-TOI ligand to target the TOI in the human to treat or prevent said disease or condition.","In an alternative where the TOI is human PCSK9, paragraph 1 provides:— A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation as defined herein (eg, I474V or E670G) in SEQ ID NO: 1, wherein the antibody comprises a VH domain derived from the recombination of a human VH segment, a human D gene segment and a human JH segment, the human VH segment encoding a valine at the amino acid corresponding to position 5 of SEQ ID NO: 40 and wherein said human comprises (i) a VH gene segment encoding the framework 1 of SEQ ID NO: 40 and (ii) a nucleotide sequence encoding a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation in SEQ ID NO: 1.In an alternative where the TOI is human PCSK9, paragraph 1 provides:— A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation as defined herein (eg, I474V or E670G) in SEQ ID NO: 1, wherein the antibody comprises a VL domain derived from the recombination of a human VL segment and a human JL segment, the human VL segment is a Vλ or Vκ disclosed herein and wherein said human comprises (i) said VL gene segment and (ii) a nucleotide sequence encoding a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation in SEQ ID NO: 1.In an alternative where the TOI is human PCSK9, paragraph 1 provides:— A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation as defined herein (eg, I474V or E670G) in SEQ ID NO: 1, wherein the antibody comprises a C domain encoded by a human CH, Cλ or Cκ gene segment disclosed herein and wherein said human comprises (i) said C gene segment and (ii) a nucleotide sequence encoding a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation in SEQ ID NO: 1.2.The method of paragraph 1, wherein before step (a) the ligand has been or is determined as being capable of specifically binding to said TOI variant.","3.The method of paragraph 1 or 2, comprising determining that the human is positive for the TOI polymorphic variant, optionally wherein the step of determining comprises determining that the human is positive for a nucleotide variant encoding said TOI variant.","4.The method of paragraph 3, wherein the step of determining comprises assaying a biological sample obtained from said human for a nucleotide polymorphism encoding said TOI polymorphic variant.","5.The method of paragraph 3 or 4, wherein the step of determining comprises assaying a biological sample obtained from said human for a protein corresponding to the TOI polymorphic variant.","6.The method of any preceding paragraph, wherein said frequency is less than 15%.","7.The method of any preceding paragraph, wherein said frequency is less than 10%.","8.The method of any preceding paragraph, wherein the ligand is capable of specifically binding to two or more different TOI variants, each being encoded by a nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.","9.A method of treating or preventing a disease or condition in a human, wherein the disease or condition is mediated by a Target of Interest (TOI), wherein the TOI is present in humans as different polymorphic variants, the method comprising a. selecting a human that is negative for a variant nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%; or that the human is negative for a TOI variant encoded by a nucleotide sequence comprising the allele having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%; and b. administering to the human an anti-TOI ligand to target the TOI variant in the human and treat or prevent said disease or condition, wherein the TOI in said human is a variant encoded by a nucleotide sequence comprising an allele having a cumulative human allele frequency of more than 50% and/or having a total human genotype frequency of more than 50%.","10.The method of paragraph 9, comprising determining that the human is positive for the TOI polymorphic variant, optionally wherein the determining comprises that the human has been or is phenotyped as positive for the most frequent TOI variant or genotyped for the nucleotide sequence thereof.","11.The method of paragraph 10, wherein determining comprises assaying for the nucleotide sequence to determine the presence of said allele.","12.The method of paragraph 11, wherein the assaying comprises nucleic acid amplification.","13.The method of paragraph 11 or 12, wherein the assaying comprises hybridization, sequencing, or next generation sequencing.","14.The method of any of paragraphs 11-13, further comprising the step of obtaining a biological sample from the human.","15.The method of any one of paragraphs 9-14, wherein the ligand has been or is determined as being capable of specifically binding to the most frequent TOI variant.","16.The method of any one of paragraphs 9-15, wherein the ligand has been or is determined as being substantially incapable of neutralising or inhibiting said TOI variant.","17.The method of any one of paragraphs 9-16, wherein the ligand is capable of specifically binding to the most frequent TOI variant.","18.The method of any one of paragraphs 9-17, wherein the ligand is capable of specifically binding to two or more different TOI variants, each being encoded by a nucleotide sequence comprising an allele having a cumulative human allele frequency of more than 50%.","19.The method of any preceding paragraph, wherein said TOI polymorphic variant has been or is determined as being present in at least two different human ethnic populations.","20.The method of any preceding paragraph, wherein said cumulative human allele frequency is the frequency in a database of naturally-occurring sequences sampled from at least 15 different human ethnic populations and comprising at least 1000 sequences.","21.The method of any of the preceding paragraphs, wherein the ligand is an antibody, antibody fragment or an affibody.","22.The method of any of the preceding paragraphs, wherein the ligand comprises a nucleotide sequence that specifically hybridises to a TOI nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50% or an RNA transcript thereof, and/or the ligand comprises a nucleotide sequence that comprises at least 10 contiguous nucleotides of a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50% or is an antisense sequence thereof.","23.The method of any of the preceding paragraphs, wherein the genome of said human comprises an allele having a cumulative human allele frequency of less than 50% and the allele is found in at least 2 different ethnic populations.","24.A composition comprising a ligand capable of binding a target of interest encoded by a nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and the allele is found in at least 2 different ethnic populations and optionally a pharmaceutically acceptable carrier and optionally a label or instructions for use to treat and/or prevent said disease or condition in a human; optionally wherein the label or instructions comprise a marketing authorisation number issued by a regulatory authority.","25.A kit for treating or preventing a condition or disease mediated by a target of interest as recited in any preceding paragraph, the kit comprising a ligand capable of specifically binding a target of interest encoded by a nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and the allele is found in at least 2 different ethnic populations; and optionally in combination with a label or instructions for use to treat and/or prevent said disease or condition in a human; optionally wherein the label or instructions comprise a marketing authorisation number issued by a regulatory agency; optionally wherein the kit comprises an injection pen or IV container that comprises the ligand.","26.The composition of paragraph 24 or the kit of paragraph 25, wherein the regulatory agency is FDA or EMA.","27.A method of producing an anti-human TOI antibody binding site, the method comprising obtaining a plurality of anti-TOI antibody binding sites, screening the antibody binding sites for binding to a TOI comprising an amino acid sequence encoded by a nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, or to a peptide thereof that comprises an amino acid variation from the corresponding sequence encoded by the TOI-encoding nucleotide sequence comprising an allele having the highest cumulative human allele frequency and/or the highest total human genotype frequency, and isolating an antibody binding site that binds in the screening step.","28.A method of producing an anti-human TOI antibody, the method comprising immunising a non-human vertebrate with a TOI comprising an amino acid sequence encoded by a nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, or to a peptide thereof that comprises an amino acid variation from the corresponding sequence encoded by the TOI-encoding nucleotide sequence comprising an allele having the highest cumulative human allele frequency and/or the highest total human genotype frequency, and isolating an antibody that binds a TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, and optionally producing a TOI-binding fragment or derivative of the isolated antibody.","29.The method of paragraph 28, wherein the non-human vertebrate is a mouse or a rat.","30.The method of paragraph 29 or 30, comprising the step of obtaining a nucleic acid encoding the antibody, fragment, derivative or binding site and optionally inserting the nucleic acid in an expression vector.","31.A kit for TOI genotyping a human, wherein the kit comprises a nucleic acid comprising a nucleotide sequence that specifically hybridises to a TOI nucleotide sequence selected having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50% or an RNA transcript thereof, and/or the nucleic acid comprises a nucleotide sequence that comprises at least 10 contiguous nucleotides of a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50% or is an antisense sequence thereof.","32.A kit for TOI genotyping or phenotyping a human, wherein the kit comprises a ligand capable of binding a target of interest encoded by a nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% or an antibody, fragment or derivative produced by the method of any one of paragraphs 28 to 30.33.The kit of paragraph 32, wherein the allele is found in at least 2 different ethnic populations.","34.Use of an anti-TOI ligand that specifically binds a human TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, in the manufacture of a medicament for treating and/or preventing a TOI-mediated disease or condition in a human whose genome comprises a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.","35.Use of an anti-TOI ligand that specifically binds a human TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, in the manufacture of a medicament for targeting said TOI in a human to treat and/or prevent a disease or condition mediated by TOI.","36.A method of targeting a Target of Interest (TOI) for treating and/or preventing a TOI-mediated disease or condition in a human, the method comprising administering an anti-TOI ligand to a human comprising a TOI nucleotide sequence comprising an allele selected as having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, whereby a TOI encoded by said nucleotide sequence is targeted.","37.The method of paragraph 36, wherein the method comprises targeting a human TOI comprising an amino acid sequence with said ligand to treat and/or prevent said disease or condition in said human, wherein said amino acid sequence is encoded by a nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%.","38.A method of Target of Interest (TOI) genotyping a nucleic acid sample of a human, the method comprising assaying in the sample the presence of a TOI nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.","39.A method of Target of Interest (TOI) typing a protein sample of a human, the method comprising assaying the sample the presence of a TOI amino acid sequence encoded by a TOI nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.","40.The method of paragraph 38 or 39, comprising obtaining a sample of serum, blood, faeces, hair, urine or saliva from a human, whereby the nucleic acid or protein sample is obtained for use in the step of assaying said sequence.","41.The method of any one of paragraphs 38-40, comprising using a ligand capable of targeting a nucleic acid sequence comprising an allele having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50% or a ligand capable of specifically binding the TOI encoded by said nucleic acid sequence to carry out said identifying step.","42.A diagnostic kit comprising a ligand that is capable of binding a human Target of Interest (TOI) comprising an amino acid sequence encoded by a TOI nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50% and instructions for carrying out the method of any one of paragraphs 38-41.43.The diagnostic kit wherein the ligand is selected from an antibody, antibody fragment, antibody portion, affybody, oligonucleotide, modified oligonucleotide, antisense oligonucleotide, siRNA, and microRNA.","44.A diagnostic kit comprising a nucleic acid probe comprising a nucleotide sequence that specifically hybridises a Target of Interest (TOI) nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50% or an RNA transcript thereof and instructions for carrying out the method of paragraph 38 or 39.45.The method, ligand, composition, kit or use of any preceding paragraph, wherein the TOI is encoded by a nucleotide sequence having a cumulative human allele frequency from 1 to 10% and/or a total human genotype frequency from 1 to about 15% or from 1 to 15%.","46.The method, ligand, composition, kit or use of any preceding paragraph wherein the TOI is a human TOI selected from Table 5; optionally for treating and/or preventing a corresponding disease or condition as set out in Table 5.47.A method of treating or preventing a disease or condition in a human, wherein the disease or condition is mediated by a Target of Interest (TOI), wherein the TOI is present in humans as different polymorphic variants, the method comprising administering to the human determined to be positive for the TOI polymorphic variant, wherein the TOI in said human is encoded by a nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and/or wherein the TOI in said human is encoded by a nucleotide sequence comprising an allele having total human genotype frequency of less than 50% an anti-TOI ligand to target the TOI in the human to treat or prevent said disease or condition.","48.The method of paragraph 47, wherein the anti-TOI ligand is selected from an antibody, an antibody portion, an antibody fragment, an affibody, an antisense oligonucleotide, an siRNA, and a microRNA.","Additional Tailoring of Ligands to Genotype and/or Phenotype of the Human Patient As described herein, the present invention contemplates ligands (eg, antibodies and fragments) whose binding site specificities have been matched to one or more variant human TOIs (eg, PCSK9 or IL6R).","Additionally or alternatively (and as further illustrated in the non-limiting Examples below), an optional aspect of the invention provides for matching of other features of the ligand to the patient's genotype or phenotype.","In this respect, for example, the invention includes the ability to match amino acid sequence variation in a human patient to one or more ligand sequences or domains outside of the binding sites.","For example, where the ligand comprises or consists of a human TOI-binding antibody or an anti-human TOI receptor Fc fusion, this aspect of the invention provides for more tailored matching of one or more constant region domains (eg, the Fc) to the patient genotype or phenotype.","Additionally or alternatively, it is contemplated that sequence variation in the binding site can be similarly matched to the patient's genotype or phenotype.","The present inventor has done this by considering the SNP occurrences in sequences encoding one or more parts of the ligand, eg, SNP occurrences in one, more or all of the gene segments from which the variable domain(s) and/or constant region domain(s) are derived.","The inventor realised that it would be desirable to match the ligand to one or more corresponding variant SNPs found in the patient to be treated therapeutically and/or prophylactically.","Matching could involve designing the ligand specifically for a patient of known phenotype and/or genotype, or matching could involve choosing a ligand by determining that there is correspondence between variation in the patient's phenotype or genotype with the variation in the ligand amino acid and/or corresponding nucleotides.","A key consideration for the inventor was the desire to promote compatibility of the ligand with the patient's body, and in particular, the possible patient immune system responses to administered ligands.","For example, it has been observed that human patients receiving human or humanised antibody drugs may mount an immune response against the incoming antibody (a so-called HAHA response) which results in the patient producing anti-drug antibodies as a result of the patient's immune system recognising the drug as foreign.","For example, studies have suggested that some patients receiving HUMIRA™ (adalimumab), currently the biggest selling antibody medicine, mount a HAHA immune response against the medicine, and this may impact treatment adversely.","Reference is made to JAMA.","2011; 305(14): 1460-1468.doi: 10.1001/jama.2011.406: “Development of Antidrug Antibodies Against Adalimumab and Association With Disease Activity and Treatment Failure During Long-term Follow-up”, G M Bartelds et al.","The authors concluded that results of this study showed that development of antidrug antibodies was associated with a negative outcome of adalimumab treatment in human RA patients.","It was reported that not only did patients with anti-adalimumab antibodies discontinue treatment more often and earlier than patients without anti-adalimumab antibodies, they also had a higher disease activity during treatment and only rarely came into remission.","In addition, reportedly the data showed that two-thirds of the anti-adalimumab antibody-positive patients developed these antibodies in the first 28 weeks of treatment and that the presence of anti-adalimumab antibodies substantially influenced serum adalimumab concentrations.","This HAHA theme is, therefore, a significant concern and this has been considered by the regulatory authorities.","For example, the European Medicines Agency (EMA) has issued a “Guideline on immunogenicity assessment of monoclonal antibodies intended for in vivo clinical use” (available on the world wide web at ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/06/WC500128688.pdf, EMA/CHMP/BMWP/86289/2010, addendum to EMEA/CHMP/BMWP/14327/2006), which came into force on 1 Dec. 2012.As such, it is good practice for researchers to identify and assess risk of anti-antibody drug occurrence and effects.","The present aspect of the invention, by more closely tailoring the ligand itself (as well as its specificity) to the patient, helps to address these considerations when designing and administering anti-human TOI medicines for treating and/or preventing human TOI-related diseases and conditions.","The inventor also considered the desirability to tailor the variation in the ligand constant region (eg, for an antibody or Fc-containing ligand), mindful that then the constant region being administered to the patient would be tuned to the various components, such as patient's Fc receptors, that would interact with the constant region in the patient.","Good Fc/Fc receptor interactions can be important for drug recycling (via the FcRn) to provide for useful half-lives in vivo or for use in cell killing, eg, for cancer indications.","In this way it is possible, therefore, to tune the effector function of the constant region (eg, Fc) to the patient more closely, to promote efficacy.","For example, more efficacious drugs are desirable for better patient treatment and may provide the possibility of lowered dosing and/or dosing frequencies.","Thus, in examples of this aspect, the invention provides the following (set out as clauses):— 1.The ligand, method, use, kit or composition of the invention, wherein (i) the ligand (eg, antibody or fragment) comprises (c) a variable domain that is encoded by a human V region nucleotide sequence, wherein the V nucleotide sequence is derived from recombination of human VH, D and JH gene segments or human VL and JL gene segments; or (d) a constant region domain encoded by a C region gene segment; Wherein a first gene segment of said gene segments of (a), or said C region gene segment of (b) comprises a first single nucleotide polymorphism (SNP) encoding a first amino acid polymorphism; and (ii) the genome of said human comprises said first SNP or wherein said human expresses (a′) an antibody variable domain comprising said first amino acid polymorphism or (b′) an antibody constant domain comprising said first amino acid polymorphism.","2.The ligand, method, use, kit or composition of clause 1, wherein blood of said human comprises substantially no antibodies that specifically bind to the domain comprising said first amino acid polymorphism as determined in an in vitro binding assay.","3.The ligand, method, use, kit or composition of clause 2, wherein SPR is used to carry out said assay.","In an alternative, ELISA is used.","4.The ligand, method, use, kit or composition of any one of clauses 1 to 3, wherein the genome of said human comprises said first gene segment (when (a) applies) or said C region gene segment (when (b) applies).","5.The ligand, method, use, kit or composition of any one of clauses 1 to 4, wherein said first segment or a second segment of said segments of (a), or said C region gene segment of (b), comprises a second SNP encoding a second amino acid polymorphism; and wherein the genome of said human comprises said second SNP or wherein said human expresses (a″) an antibody variable domain comprising said second amino acid polymorphism or (b″) an antibody constant region domain comprising said first and second amino acid polymorphisms.","6.The ligand, method, use, kit or composition of clause 5, wherein said human expresses an antibody variable domain comprising said first and second amino acid polymorphisms.","7.The ligand, method, use, kit or composition of clause 5 or 6, wherein the first and second SNPs of said genome are comprised by the same antibody gene segment.","For example, the first and second SNPs of the genome are comprised by an IGHG1*01 gene segment and said first segment of (a) is an IGHG1*01 gene segment.","For example, the first and second SNPs of the genome are comprised by an IGHG2*01 gene segment and said first segment of (a) is an IGHG2*01 gene segment.","8.The ligand, method, use, kit or composition of any one of clauses 1 to 7, wherein each SNP is a variable region gene segment SNP.","9.The ligand, method, use, kit or composition of any one of clauses 1 to 7, wherein each SNP is a constant region gene segment SNP, eg each SNP is a gamma-1 constant region gene segment SNP, or a gamma-2 constant region gene segment SNP, or a gamma-3 constant region gene segment SNP or a gamma-4 constant region gene segment SNP.","10.The ligand, method, use, kit or composition of clause 9, wherein the first SNP is a CH1, CH2, CH3 or CH4 gene segment SNP and/or the second SNP is a CH1, CH2, CH3 or CH4 gene segment SNP.","11.The ligand, method, use, kit or composition of any one of clauses 1 to 8, wherein each SNP is a variable domain SNP, eg, a VH domain SNP, or a Vκ domain SNP, or a Vλ SNP.","12.The ligand, method, use, kit or composition of any one of clauses 1 to 11, wherein said constant region domain of (b) is comprised by an antibody Fc region.","13.The ligand, method, use, kit or composition of any one of clauses 1 to 12, wherein the ligand (eg, antibody or fragment) has been determined to specifically bind one or more human TOI variants as disclosed herein, for example, with a KD of 1 nM or less (eg, 100 or 10 pM or less) as determined by SPR.","14.The ligand, method, use, kit or composition of the invention (eg, according to any one of clauses 1 to 13), wherein the ligand comprises or consists of an antibody or fragment that comprises a human antibody variable domain derived from the recombination of a human V gene segment and a human J gene segment (and optionally a human D gene segment when the variable domains are VH domains); and wherein the genome of the human comprises said human V gene segment and/or the human expresses antibodies comprising antibody variable domains derived from the recombination of said human V gene segment and a human J gene segment (and optionally a human D gene segment).","In an example, the V gene segment is any of the V gene segments disclosed in WO2013041844, a 1000 Genomes database and/or www.imgt.org, the disclosures of which (including disclosure relating to sequence) is explicitly incorporated herein by reference for use in the present invention.","15.The ligand, method, use, kit or composition of the invention (eg, according to any one of clauses 1 to 14), wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused human TOI receptor) comprises a human heavy chain constant domain encoded by a first constant region nucleotide sequence; and wherein the genome of the human comprises a heavy chain constant region nucleotide sequence that is identical to said first constant region nucleotide sequence and/or the human expresses antibodies comprising said human constant domain.","16.The ligand, method, use, kit or composition of the invention (eg, according to any one of clauses 1 to 15), wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused human TOI receptor) comprises a human gamma heavy chain CH1 domain encoded by a CH1 nucleotide sequence; and wherein the genome of the human comprises a gamma heavy chain constant region nucleotide sequence that is identical to said CH1 nucleotide sequence and/or the human expresses antibodies comprising said human gamma CH1 domain.","17.The ligand, method, use, kit or composition of the invention (eg, according to any one of clauses 1 to 16), wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused human TOI receptor) comprises a human gamma heavy chain CH2 domain encoded by a CH2 nucleotide sequence; and wherein the genome of the human comprises a gamma heavy chain constant region nucleotide sequence that is identical to said CH2 nucleotide sequence and/or the human expresses antibodies comprising said human gamma CH2 domain.","18.The ligand, method, use, kit or composition of the invention (eg, according to any one of clauses 1 to 17), wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused human TOI receptor) comprises a human gamma heavy chain CH3 domain encoded by a CH3 nucleotide sequence; and wherein the genome of the human comprises a gamma heavy chain constant region nucleotide sequence that is identical to said CH3 nucleotide sequence and/or the human expresses antibodies comprising said human gamma CH3 domain.","19.The ligand, method, use, kit or composition of the invention (eg, according to any one of clauses 1 to 18), wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused human TOI receptor) comprises a human gamma heavy chain CH4 domain encoded by a CH4 nucleotide sequence; and wherein the genome of the human comprises a gamma heavy chain constant region nucleotide sequence that is identical to said CH4 nucleotide sequence and/or the human expresses antibodies comprising said human gamma CH4 domain.","20.The ligand, method, use, kit or composition of the invention (eg, according to any one of clauses 1 to 19), wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused human TOI receptor) comprises a human gamma heavy chain Fc region encoded by a Fc nucleotide sequence; and wherein the genome of the human comprises a gamma heavy chain constant region nucleotide sequence that is identical to said Fc nucleotide sequence and/or the human expresses antibodies comprising said human gamma Fc region.","21.The ligand, method, use, kit or composition of any one of clauses 16 to 20, wherein said human gamma heavy chain is a human gamma-1 heavy chain.","22.The ligand, method, use, kit or composition of any one of clauses 16 to 20, wherein said human gamma heavy chain is a human gamma-2 heavy chain.","23.The ligand, method, use, kit or composition of any one of clauses 16 to 20, wherein ligand comprises a human IGHG1*01 gamma-1 heavy chain constant region.","24.The ligand, method, use, kit or composition of any one of clauses 16 to 20, wherein ligand comprises a human IGHG2*01 gamma-1 heavy chain constant region.","25.The ligand, method, use, kit or composition of any one of clauses 15 to 24, wherein the human has been or is genotyped as positive for said heavy chain constant region nucleotide sequence.","26.The ligand, method, use, kit or composition of clause 23, wherein the human has been or is genotyped as positive for human IGHG1*01 nucleotide sequence.","27.The ligand, method, use, kit or composition of clause 24, wherein the human has been or is genotyped as positive for human IGHG2*01 nucleotide sequence.","28.The ligand, method, use, kit or composition of any one of clauses 16 to 24, wherein the human has been or is phenotyped as positive for said gamma heavy chain constant domain, CH1, CH2, CH3, CH4 or Fc.","29.The ligand, method, use, kit or composition of clause 28, (i) when dependent from clause 23, wherein the human has been or is phenotyped as positive for a human IGHG1*01 gamma heavy chain constant domain, CH1, CH2, CH3, CH4 or Fc or (ii) when dependent from clause 24, wherein the human has been phenotyped as positive for a human IGHG2*01 gamma heavy chain constant domain, CH1, CH2, CH3, CH4 or Fc.","30.The method or use of any one of clauses 16 to 24 and 26 to 29, comprising genotyping the human as positive for said gamma heavy chain constant region nucleotide sequence, eg, positive for said gamma heavy chain constant domain, CH1, CH2, CH3, CH4 or Fc nucleotide sequence; positive for said human IGHG1*01 gamma heavy chain constant region, CH1, CH2, CH3, CH4 or Fc nucleotide sequence; or positive for said human IGHG2*01 gamma heavy chain constant region, CH1, CH2, CH3, CH4 or Fc nucleotide sequence.","31.The method or use of any one of clauses 16 to 24 and 26 to 30, comprising phenotyping the human as positive for said gamma heavy chain constant region, eg, positive for said gamma heavy chain constant domain, CH1, CH2, CH3, CH4 or Fc; positive for said human IGHG1*01 gamma heavy chain constant domain, CH1, CH2, CH3, CH4 or Fc; or positive for said human IGHG2*01 gamma heavy chain constant domain, CH1, CH2, CH3, CH4 or Fc.","Examples of Tailored Ligands The inventor analysed amino acid variability and distribution amongst large representative human samples.","The result of the analysis for example antibody gene segments is shown in Table 9.In a first example, the inventor identified the possibility of addressing the rarer IGH-gamma-1 SNPs 204D (observed cumulative frequency of 0.296) and 206L (observed cumulative frequency of 0.283) individually or in combination.","These residues are part of the CH3 domain, and as such they form part of antibody Fc regions.","Thus, matching of these CH3 variations with the patient is especially beneficial for reasons as discussed above.","Thus, this example provides aspects set out in the following clauses.","32.The ligand, method, use, kit or composition of the invention (eg, according to any one of clauses 1 to 31), wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused TOI receptor) comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 or a Leu corresponding to position 206 of SEQ ID NO: 42 and wherein the genome of the human comprises a gamma-1 heavy chain constant region nucleotide sequence that encodes such an Asp or Leu or the human expresses antibodies comprising human gamma-1 constant regions comprising such an Asp or Leu.","The skilled person will be familiar with techniques for determining genome sequences of a human, eg, by using a sample containing genomic DNA and/or RNA, sequencing and comparing using bioinformatics or other computer tools to compare the sampled sequence with sequences of human alleles (eg, as shown in the IMGT, 100 genomes or other database as disclosed herein).","In an example, the sample is a blood or saliva or cheek swab sample.","33.The ligand, method, use, kit or composition of clause 32, wherein the ligand comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 and a Leu corresponding to position 206 of SEQ ID NO: 42.34.The ligand, method, use, kit or composition of clause 32 or 33, wherein the genome of the human comprises a gamma-1 heavy chain constant region nucleotide sequence that encodes such an Asp and Leu or the human expresses antibodies comprising human gamma-1 constant regions comprising such an Asp and Leu.","35.The ligand, method, use, kit or composition of clause 32, 33 or 34, wherein the ligand comprises a human IGHG1*01 gamma-1 heavy chain constant region, eg, an Fc, CH1, CH2 and/or CH3 domain encoded by human IGHG1*01.36.The ligand, method, use, kit or composition of any one of clauses 32 to 35, wherein the genome of the human comprises a human IGHG1*01 nucleotide sequence or the human expresses antibodies comprising human constant domains encoded by a human IGHG1*01 nucleotide sequence.","37.The ligand, method, use, kit or composition of any one of clauses 32 to 36, wherein the ligand comprises a hinge region encoded by human IGHG1*01.38.The ligand, method, use, kit or composition of any one of clauses 32 to 37, wherein the ligand comprises or consists of an antibody, wherein the antibody comprises heavy chains that comprise SEQ ID NO: 61.39.The ligand, method, use, kit or composition of any one of clauses 32 to 38, wherein the human is of European ancestry.","As shown in Table 9, 204D and 206L are found in such humans.","40.The ligand, method, use, kit or composition of any one of clauses 32 to 39, wherein the human has been or is genotyped as positive for said Asp and/or Leu.","41.The ligand, method, use, kit or composition of any one of clauses 32 to 40, wherein the human has been or is genotyped as positive for human IGHG1*01.42.The ligand, method, use, kit or composition of any one of clauses 32 to 41, wherein the human has been or is phenotyped as positive for a human IGHG1*01 CH3.43.The method or use of any one of clauses 32 to 42, comprising selecting a said human whose genome comprises a codon(s) encoding said Asp and/or Leu; comprises human IGHG1*01; or comprises a human IGHG1*01 CH3.44.The method or use of any one of clauses 32 to 43, comprising selecting a said human whose phenotype comprises said Asp and/or Leu; a human IGHG1*01 region; or a human IGHG1*01 CH3.44a.","The ligand, method, use, kit or composition of any one of clauses 32 to 44, wherein the human expresses antibodies comprising human gamma-1 constant regions comprising such an Asp and Leu.","In a second example, the inventor identified the possibility of addressing IGH-gamma-2 SNPs.","This included consideration of Fc region variation—in this respect, the inventor focused on positions 161 and 257 which are in the Fc region.","Thus, this example provides aspects set out in the following clauses.","45.The ligand, method, use, kit or composition of the invention (eg, according to any one of clauses 1 to 31), wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused TOI receptor) comprises a human gamma-2 heavy chain constant region that comprises an amino acid selected from the group consisting of a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44, a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44; and wherein the genome of the human comprises a gamma-2 heavy chain constant region nucleotide sequence that encodes such a selected amino acid or the human expresses antibodies comprising human gamma-2 constant regions comprising such a selected amino acid.","46.The ligand, method, use, kit or composition of clause 45, wherein the ligand comprises a human gamma-2 heavy chain constant region that comprises (i) a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44 and optionally (ii) a Val corresponding to position 161 of SEQ ID NO: 44 and/or an Ala corresponding to position 257 of SEQ ID NO: 44; and wherein the genome of the human comprises a gamma-2 heavy chain constant region nucleotide sequence that encodes such amino acids of (i) or the human expresses antibodies comprising human gamma-2 constant regions comprising such amino acids of (i).","This example focuses on CH1 variation.","47.The ligand, method, use, kit or composition of clause 45 or 46, wherein the ligand comprises a human gamma-2 heavy chain constant region that comprises (i) a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44 and optionally (ii) an amino acid selected from the group consisting of a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44 and a Phe corresponding to position 76 of SEQ ID NO: 44; and wherein the genome of the human comprises a gamma-2 heavy chain constant region nucleotide sequence that encodes such amino acids of (i) or the human expresses antibodies comprising human gamma-2 constant regions comprising such amino acids of (i).","This example focuses on Fc variation.","48.The ligand, method, use, kit or composition of any one of clauses 45 to 47, wherein the ligand comprises a human IGHG2*01 gamma-2 heavy chain constant region, eg, an Fc, CH1, CH2 and/or CH3 domain encoded by human IGHG2*01.49.The ligand, method, use, kit or composition of any one of clauses 45 to 48, wherein the genome of the human comprises a human IGHG2*01 nucleotide sequence or the human expresses antibodies comprising human constant domains encoded by a human IGHG2*01 nucleotide sequence.","50.The ligand, method, use, kit or composition of any one of clauses 45 to 49, wherein the ligand comprises a hinge region encoded by human IGHG2*01.51.The ligand, method, use, kit or composition of any one of clauses 45 to 50, wherein the ligand comprises or consists of an antibody, wherein the antibody comprises heavy chains that comprise SEQ ID NO: 63 or 65.52.The ligand, method, use, kit or composition of any one of clauses 45 to 51, wherein the human is of European, African American, or European American ancestry.","53.The ligand, method, use, kit or composition of any one of clauses 45 to 52, wherein the human has been or is genotyped as positive for one, more or all of said Pro, Asn, Phe, Val and Ala. 54.The ligand, method, use, kit or composition of any one of clauses 45 to 53, wherein the human has been or is genotyped as positive for human IGHG2*01.55.The ligand, method, use, kit or composition of any one of clauses 45 to 54, wherein the human has been or is phenotyped as positive for a human IGHG2*01 CH1.56.The ligand, method, use, kit or composition of any one of clauses 45 to 55, wherein the human has been or is phenotyped as positive for a human IGHG2*01 CH2.57.The ligand, method, use, kit or composition of any one of clauses 45 to 56, wherein the human has been or is phenotyped as positive for a human IGHG2*01 CH3.58.The method or use of any one of clauses 45 to 57, comprising selecting a said human whose genome comprises a codon(s) encoding one, more or all of said Pro, Asn, Phe, Val and Ala; comprises human IGHG2*01; or comprises a human IGHG2*01 CH1, CH2 and/or CH3.59.The method or use of any one of clauses 45 to 58, comprising selecting a said human whose phenotype comprises one, more or all of said Pro, Asn, Phe, Val and Ala; a human IGHG2*01 region; or a human IGHG2*01 CH1, CH2 and/or CH3.60.The ligand, method, use, kit or composition of any one of clauses 45 to 59, wherein the human expresses antibodies comprising human gamma-2 constant regions comprising such a Pro, Asn, Phe, Val and Ala.","In a third example, the inventor addressed human kappa constant region variation.","Thus, the present aspect of the invention also provides the following.","61.The ligand, method, use, kit or composition of the invention (eg, according to any one of clauses 1 to 60), wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused TOI receptor) comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 or a Cys corresponding to position 87 of SEQ ID NO: 50; and wherein the genome of the human comprises a kappa light chain constant region nucleotide sequence that encodes such a Val or Cys or the human expresses antibodies comprising human kappa light chain constant regions comprising such a Val or Cys.","62.The ligand, method, use, kit or composition of clause 61, wherein the ligand comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 and a Cys corresponding to position 87 of SEQ ID NO: 50.63.The ligand, method, use, kit or composition of clause 61 or 62, wherein the genome of the human comprises a kappa light chain constant region nucleotide sequence that encodes such a Val and Cys or the human expresses antibodies comprising human kappa constant regions comprising such a Val and Cys.","64.The ligand, method, use, kit or composition of any one of clauses 61 to 63, wherein the antibody or fragment comprises a human IGKC*01 kappa light chain constant region.","65.The ligand, method, use, kit or composition of any one of clauses 61 to 64, wherein the ligand comprises or consists of an antibody, wherein the antibody comprises light chains that comprise SEQ ID NO: 62 or 66.66.The ligand, method, use, kit or composition of any one of clauses 61 to 65, wherein the ligand comprises or consists of an antibody, wherein the antibody comprises a light chain variable domain derived from recombination of a human Vκ gene segment and a human Jκ gene segment, wherein the Jκ gene segment is IGKJ2*01 (SEQ ID NO: 57).","67.The ligand, method, use, kit or composition of any one of clauses 61 to 66, wherein the human has been or is phenotyped as positive for said Val and/or Cys.","68.The ligand, method, use, kit or composition of any one of clauses 61 to 67, wherein the human has been or is genotyped as positive for human IGKC*01.69.The ligand, method, use, kit or composition of any one of clauses 61 to 68, wherein the human has been or is phenotyped as positive for a human IGKC*01 domain.","70.The method or use of any one of clauses 61 to 69, comprising selecting a said human whose genome comprises a codon(s) encoding said Val and/or Cys; or comprises human IGKC*01.71.The method or use of any one of clauses 61 to 70, comprising selecting a said human whose phenotype comprises such a Val and/or Cys; or comprises a human IGKC*01 domain.","72.The ligand, method, use, kit or composition of any one of clauses 61 to 71, wherein the human expresses antibodies comprising human kappa constant domains comprising such a Val and Cys, eg, expresses human IGKC*01 constant domains.","In a fourth example, the inventor addressed human lambda constant region variation.","Thus, this example provides aspects set out in the following clauses.","73.The ligand, method, use, kit or composition of the invention (eg, according to any one of clauses 1 to 60), wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused TOI receptor) comprises a human IGLC2*01 light chain constant region; and wherein the genome of the human comprises a human IGLC2*01 nucleotide sequence or the human expresses antibodies comprising human light chain IGLC2*01 constant regions.","74.The ligand, method, use, kit or composition of clause 73, wherein the antibody comprises light chains that comprise SEQ ID NO: 64.75.The ligand, method, use, kit or composition of clause 73 or 74, wherein the human has been or is genotyped as positive for human IGLC2*01.76.The ligand, method, use, kit or composition of any one of clauses 73 to 75, wherein the human has been or is phenotyped as positive for a human IGLC2*01 domain.","77.The method or use of any one of clauses 73 to 76, comprising selecting a said human whose genome comprises human IGLC2*01.78.The method or use of any one of clauses 73 to 77, comprising selecting a said human whose phenotype comprises a human IGLC2*01 domain.","79.The ligand, method, use, kit or composition of any one of clauses 73 to 78, wherein the human expresses antibodies comprising human lambda IGLC2*01 constant domains.","In a fifth example, the inventor addressed human heavy chain variable region variation.","Thus, this example provides aspects set out in the following clauses.","80.The ligand, method, use, kit or composition of the invention (eg, according to any one of clauses 1 to 79), wherein the ligand comprises or consists of an antibody or fragment, wherein the antibody or fragment comprises a VH domain that is derived from the recombination of a human VH gene segment, a human D gene segment and a human JH gene segment, wherein the VH gene segment is selected from the group consisting of (i) IGHV1-18*01 and the genome of the human comprises a human IGHV1-18*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGHV1-18*01; or (ii) IGVH1-46*01 and the genome of the human comprises a human IGHV1-46*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGHV1-46*01.81.The ligand, method, use, kit or composition of clause 80, wherein the antibody or fragment comprises a one more or all of a CH1 domain, CH2 domain, CH3 domain, hinge or Fc encoded by human IGHG2*01.82.The ligand, method, use, kit or composition of clause 80 or 81, wherein the antibody or fragment comprises heavy chains that comprise SEQ ID NO: 63 or 65.83.The ligand, method, use, kit or composition of any one of clauses 80 to 82, wherein the human has been or is genotyped as positive for said selected VH gene segment, positive for human IGHV1-18*01 or IGVH1-46*01.84.The method or use of any of clauses 80 to 83, comprising genotyping the human as positive for said selected VH gene segment, eg, positive for human IGHV1-18*01 or IGVH1-46*01.In a sixth example, the inventor addressed human light chain variable region variation.","Thus, this example provides aspects set out in the following clauses.","85.The ligand, method, use, kit or composition of the invention (eg, according to any one of clauses 1 to 84), wherein the ligand comprises or consists of an antibody or fragment, wherein the antibody or fragment comprises a VL domain that is derived from the recombination of a human VL gene segment and a human JL gene segment, wherein the VL gene segment is selected from the group consisting of (i) IGKV4-1*01 and the genome of the human comprises a human IGKV4-1*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGKV4-1*01; (ii) IGLV2-14*01 and the genome of the human comprises a human IGLV2-14*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGLV2-14*01; or (iii) IGKV1-13*02 and the genome of the human comprises a human IGKV1-13*02 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGKV1-13*02.86.The ligand, method, use, kit or composition of clause 85, wherein the antibody comprises light chains that comprise SEQ ID NO: 62, 64 or 66.87.The ligand, method, use, kit or composition of clause 85 or 86, wherein the antibody or fragment comprises a light chain variable domain derived from recombination of a human Vκ gene segment and a human Jκ gene segment, wherein the Jκ gene segment is IGKJ2*01 (SEQ ID NO: 57; wherein (i) or (iii) applies.","88.The ligand, method, use, kit or composition of any one of clauses 85 to 87, wherein the human has been or is genotyped as positive for said selected VL gene segment, eg, positive for human IGKV4-1*01, IGLV2-14*01 or IGKV1-13*02.89.The method or use of clause 88, comprising genotyping the human as positive for said selected VL gene segment, eg, genotyping the human as positive for human IGKV4-1*01, IGLV2-14*01 or IGKV1-13*02.90.The ligand, method, use, kit or composition of any one of clauses 1 to 89, wherein the ligand (eg, antibody or fragment) binds said human TOI with a dissociation constant (Kd) of 1 nM or less as determined by SPR, (eg, 100, 10 or 1 pM or less).","EXAMPLES Example 1: Rare PCSK9 Variants Proprotein convertase subtilisin kexin type 9 (PCSK9) is a serine protease involved in regulating the levels of the low density lipoprotein receptor (LDLR) protein (Horton et al., 2007; Seidah and Prat, 2007).","In vitro experiments have shown that adding PCSK9 to HepG2 cells lowers the levels of cell surface LDLR (Benjannet et al., 2004; Lagace et al., 2006; Maxwell et al., 2005; Park et al., 2004).","Experiments with mice have shown that increasing PCSK9 protein levels decreases levels of LDLR protein in the liver (Benjannet et al., 2004; Lagace et al., 2006; Maxwell et al., 2005; Park et al., 2004), while PCSK9 knockout mice have increased levels of LDLR in the liver (Rashid et al., 2005).","Additionally, various human PCSK9 mutations that result in either increased or decreased levels of plasma LDL have been identified (Kotowski et al., 2006; Zhao et al., 2006).","PCSK9 has been shown to directly interact with the LDLR protein, be endocytosed along with the LDLR, and co-immunofluoresce with the LDLR throughout the endosomal pathway (Lagace et al., 2006).","PCSK9 is a prohormone-proprotein convertase in the subtilisin (S8) family of serine proteases (Seidah et al., 2003).","Humans have nine prohormone-proprotein convertases that can be divided between the S8A and S8B subfamilies (Rawlings et al., 2006).","Furin, PC1/PC3, PC2, PACE4, PC4, PC5/PC6 and PC7/PC8/LPC/SPC7 are classified in subfamily S8B.","Crystal and NMR structures of different domains from mouse furin and PC1 reveal subtilisin-like pro- and catalytic domains, and a P domain directly C-terminal to the catalytic domain (Henrich et al., 2003; Tangrea et al., 2002).","Based on the amino acid sequence similarity within this subfamily, all seven members are predicted to have similar structures (Henrich et al., 2005).","SKI-1/SIP and PCSK9 are classified in subfamily S8A.","Sequence comparisons with these proteins also suggest the presence of subtilisin-like pro- and catalytic domains (Sakai et al., 1998; Seidah et al., 2003; Seidah et al., 1999).","In these proteins the amino acid sequence C-terminal to the catalytic domain is more variable and does not suggest the presence of a P domain.","Prohormone-proprotein convertases are expressed as zymogens and they mature through a multi step process.","The function of the pro-domain in this process is two-fold.","The pro-domain first acts as a chaperone and is required for proper folding of the catalytic domain (Ikemura et al., 1987).","Once the catalytic domain is folded, autocatalysis occurs between the pro-domain and catalytic domain.","Following this initial cleavage reaction, the pro-domain remains bound to the catalytic domain where it then acts as an inhibitor of catalytic activity (Fu et al., 2000).","When conditions are correct, maturation proceeds with a second autocatalytic event at a site within the pro-domain (Anderson et al., 1997).","After this second cleavage event occurs the pro-domain and catalytic domain dissociate, giving rise to an active protease.","Autocatalysis of the PCSK9 zymogen occurs between Gln152 and Ser153 (VFAQ|SIP (SEQ ID NO: 67)) (Naureckiene et al., 2003), and has been shown to be required for its secretion from cells (Seidah et al., 2003).","A second autocatalytic event at a site within PCSK9's pro-domain has not been observed.","Purified PCSK9 is made up of two species that can be separated by non-reducing SDS-PAGE; the pro-domain at 17 Kd, and the catalytic plus C-terminal domains at 65 Kd.","PCSK9 has not been isolated without its inhibitory pro-domain, and measurements of PCSK9's catalytic activity have been variable (Naureckiene et al., 2003; Seidah et al., 2003).","In certain embodiments, a PCSK9 polypeptide includes terminal residues, such as, but not limited to, leader sequence residues, targeting residues, amino terminal methionine residues, lysine residues, tag residues and/or fusion protein residues.","“PCSK9” has also been referred to as FH3, NARC1, HCHOLA3, proprotein convertase subtilisin/kexin type 9, and neural apoptosis regulated convertase 1.The PCSK9 gene encodes a proprotein convertase protein that belongs to the proteinase K subfamily of the secretory subtilase family.","The term “PCSK9” denotes both the proprotein and the product generated following autocatalysis of the proprotein.","When only the autocatalyzed product is being referred to (such as for an antigen binding protein or ligand that binds to the cleaved PCSK9), the protein can be referred to as the “mature,” “cleaved”, “processed” or “active” PCSK9.When only the inactive form is being referred to, the protein can be referred to as the “inactive”, “pro-form”, or “unprocessed” form of PCSK9.The term PCSK9 also encompasses PCSK9 molecules incorporating post-translational modifications of the PCSK9 amino acid sequence, such as PCSK9 sequences that have been glycosylated, PCSK9 sequences from which its signal sequence has been cleaved, PCSK9 sequence from which its pro domain has been cleaved from the catalytic domain but not separated from the catalytic domain (see, e.g., FIGS.","1A and 1B of US20120093818A1; which is incorporated by reference herein in its entirety).","The present invention provides anti-PCSK9 ligands; and PCSK9-binding or targeting ligands as described herein.","The ligands have a variety of utilities.","Some of the ligands, for instance, are useful in specific binding assays, for genotyping or phenotyping humans, affinity purification of PCSK9, in particular human PCSK9 or its ligands and in screening assays to identify other antagonists of PCSK9 activity.","Some of the ligands of the invention are useful for inhibiting binding of PCSK9 to LDLR, or inhibiting PCSK9-mediated activities.","Anti-PCSK9 ligands (eg, antibodies and anti-sense RNA) have been developed based on targeting and neutralising so-called “wild-type” human PCSK9, which is a commonly-occurring form (see, eg, US20120093818A1 and US20110065902A1; each of which is incorporated by reference herein in its entirety).","While such therapies are useful for human patients harbouring this form of human PCSK9, the inventor considered it useful to investigate the possibility of targeting much rarer—but still naturally-occurring—forms of PCSK9 amongst human populations.","In this way, the inventor arrived at insight into the natural occurrences and distributions of rarer human PCSK9 forms that can serve as useful targets (at the protein or nucleic acid level) for human treatment, prophylaxis and diagnosis pertinent to diseases and conditions mediated or associated with PCSK9 activity.","This particularly provides for tailored therapies, prophylaxis and diagnosis in humans that are devoid of the common PCSK9 gene or protein (ie, the form a or a′ as used in US20120093818A1 and US20110065902A1 to generate antibodies).","The skilled person will know that SNPs or other changes that translate into amino acid variation can cause variability in activity and/or conformation of human targets to be addressed.","This has spawned great interest in personalized medicine where genotyping and knowledge of protein and nucleotide variability is used to more effectively tailor medicines and diagnosis of patients.","The invention, therefore, provides for tailored pharmaceuticals and testing that specifically addresses rarer PCSK9 polymorphic variant forms.","Such forms or “alleles” (at the nucleotide level), in many of the examples determined by the inventor, comprise multiple changes at the nucleotide and amino acid levels from the corresponding common form nucleotide and amino acids sequences, ie, there are multiple non-synonymous changes at the nucleotide level that translate into multiple corresponding changes in the protein target in humans.","Furthermore, the inventor surprisingly realised that the rarer natural forms, although present in humans at much lower frequencies than the common form, nevertheless are represented in multiple and ethnically-diverse human populations and usually with many human examples per represented ethnic population.","Thus, the inventor realised that targeting such rarer forms would provide for effective treatment, prophylaxis or diagnosis across many human ethnic populations, thereby extending the utility of the present invention.","With this realisation, the inventor realised that there is significant industrial and medical application for the invention in terms of guiding the choice of anti-PCSK9 ligand for administration to human patients for therapy and/or prophylaxis of PCSK9-mediated or associated diseases or conditions.","In this way, the patient receives drugs and ligands that are tailored to their needs—as determined by the patient's genetic or phenotypic makeup.","Hand-in-hand with this, the invention provides for the genotyping and/or phenotyping of patients in connection with such treatment, thereby allowing a proper match of drug to patient.","This increases the chances of medical efficacy, reduces the likelihood of inferior treatment using drugs or ligands that are not matched to the patient (eg, poor efficacy and/or side-effects) and avoids pharmaceutical mis-prescription and waste.","In developing this thinking, the present inventor decided to determine a set of human PCSK9 variants on the basis of the following criteria, these being criteria that the inventor realised would provide for useful medical drugs and diagnostics to tailored need in the human population.","The inventor selected variants having at least 3 of the 4 following criteria:— PCSK9 variants having a cumulative human allele frequency in the range from 1 to 10%; PCSK9 variants having a total human genotype frequency in the range from 1 to about 15%; PCSK9 variants found in many different human ethnic populations (using the standard categorisation of the 1000 Genomes Project, which is an accepted standard in the art; see Table 4 below); and PCSK9 variants found in many individuals distributed across such many different ethnic populations.","On the basis of these criteria, the inventor identified the variants listed in Table 1 below (excluding form a).","The inventor's selection included, as a consideration, selection for nucleotide variation that produced amino acid variation in corresponding PCSK9 forms (ie, non-synonymous variations), as opposed to silent variations that do not alter amino acid residues in the target protein.","TABLE 1 Human PCSK9 variants distributed over several human ethnic populations & having a total human genotype frequency in the range of 1 to about 15% (a) Amino acid variability, population distributions and frequencies ASW, YRI, GBR, 0.4506 TSI, CLM, CHB, (0.8457) LWK, CHS, MXL, Hom JPT, PUR, IBS, FIN, Freq4 Form a 46R 53A 425N 443A 474I 619Q 670E CEU 939 14 (Het + Variant Amino Acid Position & Variation Human No.","No.","Unique 0.3951 Hom 0.64815 Form 46L 53V 425S 443T 474V 619P 670G Populations Individs1 Pops2 Het Freq3 freq5) Cum Freq6 f x ASW, YRI, GBR, 180 12 0.153 0.009 0.0855 TSI, CLM, LWK, MXL, (0.162) JPT, PUR, IBS, FIN, CEU c x ASW, YRI, GBR, 153 12 0.1296 0.0081 0.0729 TSI, CLM, CHB, (0.1377) LWK, CHS, JPT, PUR, FIN, CEU r x x 0.0234 0.009 0.0292 (0.0324) p x x ASW, GBR, TSI, 49 9 0.0441 (0.0441) 0.0221 CLM, JPT, PUR, IBS, FIN, CEU m x LWK, ASW, YRI, 29 4 0.0225 (0.0225) 0.0149 CLM e x x LWK, ASW, YRI 15 3 0.0135 (0.0135) 0.0068 h x x LWK, ASW, YRI 10 3 0.009 (0.009) 0.0045 aj X x PUR, TSI, FIN, CEU 9 4 0.0081 (0.0081) 0.0041 q x x CHS, ASW, JPT, 7 5 0.0063 (0.0063) 0.0032 PUR, CHB Table Footnotes: “x” in a box indicates that the amino acid for the variant form is different from the amino acid at that position in form a, the variant amino acid being shown in “Amino Acid Position & Variation” of the table and the form a amino acid being shown in the first row of the table; amino acids at all other positions of each variant form are identical to those found in form a. Amino acid numbering is per the numbering shown for the pro-form in Table 2 below.","1Number of individuals in 1000 Genomes database found to have the allele; 2Number of unique human ethnic populations in 1000 Genomes database in which the allele was found to occur; 3Heterozygous human genotype frequency, ie, cumulative frequency of all genotypes having one occurrence of the variant allele and one occurrence of another allele (heterozygous state), eg, ac genotype in 1000 Genomes database; 4Homozygous human genotype frequency, ie, cumulative frequency of two occurrences of the variant allele (homozygous state), eg, cc genotype in 1000 Genomes database; and 5Total human genotype frequency, ie, total of heterozygous plus homozygous human genotype frequencies.","6Cumulative human allele frequency of all occurrences of the variant allele in 1000 Genomes database.","Form a′ is identical to form a with the exception that form a′ has a glycine (G) at position 620 (see US20120093818 (Amgen, Inc)); form a has E at this position.","(b) Nucleotide Sequence Variations of Selected Alleles Allele a G C A G A A A Nucleotide Position1 1:55505647 1:55505668 1:55523802 1:55523855 1:55524237 1:55527222 1:55529187 Non-Synonymous Nucleotide Variation2 T T G A G C G Variant ID3 rs11591147 rs11583680 rs28362261 rs28362263 rs562556 rs28362277 rs505151 Corresponding Amino Acid Variation Variant Allele 46L 53V 425S 443T 474V 619P 670G f X c X r X X p X X m X e X X h X X aj X X q X X “x” in a box indicates that a variant allele comprises the non-synonymous nucleotide variation indicated in the 5th row.","Table Footnotes: 1Notation is chromosome number (all positions are on human chromosome 1): coordinate number (Ensembl release 73 - September 2013, Genome assembly: GRCh37 (GCA_000001405.13); 2Nucleotide change (compared to allele a nucleotide shown in first row) giving rise to an amino acid change in the variant form (compared to amino acid of allele a); and 3NCBI dbSNP reference number (NCBI dbSNP Build 138 released on Apr.","25, 2013).","TABLE 2 Sequences (a) Human PCSK9 Form a Amino Acid Sequence (SEQ ID NO: 1) - “Pro-form” with Signal Sequence 46 53 MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP WRLPGTYVVVLKEETHLSQSERTARRLQAQPARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtligleffirksqlvqpvgplvvllplaggysrvlnascqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgedilgassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ Italics = signal sequence 1-30 Courier = pro peptide 31-152 lower case = catalytic domain 153-449 UPPER CASE = C-terminal domain 450-692 Underlined = residues changed from allele a in other sequences (aa residue number shown) The pro-form is the sequence from amino acid number 31 to (and including) amino acid number 692 of SEQ ID NO: 1.The mature form is the sequence from amino acid number 153 to (and including) amino acid number 692 of SEQ ID NO: 12 (b) Human PCSK9 Form α Amino Acid Sequence (SEQ ID NO: 3) - “Mature-form” (Numbering and notation as per SEQ ID NO: 1 above has been retained) sipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvinaacqrlaragvvlvtaagnfrddady spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqlihfsak 425 443 474 dvineawfpedqrvtpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ (c) Human PCSK9 Allele a Nucleotide Sequence (SEQ ID NO: 28) - Encoding “Pro-form” Plus Signal Sequence ATGGGCACCGTCAGCTCCAGGCGGTCCTGGTGGCCGCTGCCACTGCTGCTGCTGCTGCTGCTGCTCCTGGGTC R46L CGT to CTT CCGCGGGCGCCCGTGCGCAGGAGGACGAGGACGGCGACTACGAGGAGCTGGTGCTAGCCTTGCGTTCCG A53V GCC to GTC AGGAGGACGGCCTGGCCGAAGCACCCGAGCACGGAACCACAGCCACCTTCCACCGCTGCGCCAAGGAT CCGTGGAGGTTGCCTGGCACCTACGTGGTGGTGCTGAAGGAGGAGACCCACCTCTCGCAGTCAGAGCG CACTCCCCGCCGCCTGCAGGCCCAGGCTGCCCGCCGGGGATACCTCACCAAGATCCTGCATGTCTTCC ATGGCCTTCTTCCTGGCTTCCTGGTGAAGATGAGTGGCGACCTGCTGGAGTGGCCTTGAAGTTGCCC CATGTCGACTACATCGAGGAGGACTCCTCTGTCTTTGCCCAGagcattcccgtggaacctggagcggattacccctcca cggtaccgggcggatgaataccagccccccgacggaggcagcctggtggaggtgtatctcctagacaccagcatacagagtgaccaccgggaa atcgagggcagggtcatggtcaccgacttcgagaatgtgcccgaggaggacgggacccgcttccacagacaggccagcaagtgtgacagtcat ggcacccacctggcaggggtggtcagcggccgggatgccggcgtggccaagggtgccagcatgcgcagcctgcgcgtgctcaactgccaaggg aagggcacggttagcggcaccctcataggcctggagtttattcggaaaagccagctggtccagcctgtggggccactggtggtgctgctgcccct ggcgggtgggtacagccgcgtcctcaacgccgcctgccagcgcctggcgagggctggggtcgtgctggtcaccgctgccggcaacttccgggac gatgcctgcctctactccccagcctcagctcccgaggtcatcacagttggggccaccaatgcccaagaccagccggtgaccctggggactttggg gaccaactttggccgctgtgtggacctctttgccccaggggaggacatcattggtgcctccagcgactgcagcacctgctttgtgtcacagagtgg gacatcacaggctgctgcccacgtggctggcattgcagccatgatgctgtctgccgagccggagctcaccctggccgagttgaggcagagactg N425s AAT to AGT A443T GCC to ACC atccacttctctgccaaagatgtcatcaatgaggcctggttccctgaggaccagcgggtactgacccccacctggtggccgccctgccccccag caccatGGGGCAGGTTGGCAGCTGTTTTGCAGGACTGTATGGTCAGCACACTCGGGGCCTACACGGATGGCC I474V ATC to GTC ACAGCCATCGCCCGCTGCGCCCCAGATGAGGAGCTGCTGAGCTGCTCCAGTTTCTCCAGGAGTGGGAAGCGG CGGGGCGAGCGCATGGAGGCCCAAGGGGGCAAGCTGGTCTGCCGGGCCCACAACGCTTTTGGGGGTGAGG GTGTCTACGCCATTGCCAGGTGCTGCCTGCTACCCCAGGCCAACTGCAGCGTCCACACAGCTCCACCAGCTGA GGCCAGCATGGGGACCCGTGTCCACTGCCACCAACAGGGCCACGTCCTCACAGGCTGCAGCTCCCACTGGGA GGTGGAGGACCTTGGCACCCACAAGCCGCCTGTGCTGAGGCCACGAGGTCAGCCCAACCAGTGCGTGGGCC ACAGGGAGGCCAGCATCCACGCTTCCTGCTGCCATGCCCCAGGTCTGGAATGCAAAGTCAAGGAGCATGGAA Q619P CAG to CCG E620G GAG to GGG TCCCGGCCCCTCAGGAGCAGGTGACCGTGGCCTGCGAGGAGGGCTGGACCCTGACTGGCTGCAGTGCCCTCC CTGGGACCTCCCACGTCCTGGGGGCCTACGCCGTAGACAACACGTGTGTAGTCAGGAGCCGGGACGTCAGCA E670G GAG to GGG CTACAGGCAGCACCAGCGAAGAGGCCGTGACAGCCGTTGCCATCTGCTGCCGGAGCCGGCACCTGGCGCAG GCCTCCCAGGAGCTCCAGTGAC Italics = nucleotide sequence encoding signal sequence (nucleotides 1-90) Courier = nucleotide sequence encoding pro peptide (nucleotides 91-456) lower case = nucleotide sequence encoding catalytic domain (nucleotides 457-1346) UPPER CASE = nucleotide sequence encoding C-terminal domain (nucleotides 1347-2076) Underlined = allelic variations from allele a in other sequences (aa residue number changes and codon changes shown) The pro-form is encoded by nucleotide sequence from nucleotide 91 to (and including) nucleotide 2076.The mature form is encoded by nucleotide sequence from nucleotide 457 to (and including) nucleotide 2076.Variant Allele Nucleotide Sequences Thus, (i) The nucleotide sequence of allele f is identical to SEQ ID NO: 28 except that the nucleotide sequence of allele f comprises a GTC codon instead of an ATC codon at the position labelled “I474V” in SEQ ID NO: 28; (ii) The nucleotide sequence of allele c is identical to SEQ ID NO: 28 except that the nucleotide sequence of allele c comprises a GGG codon instead of an GAG codon at the position labelled “E670G” in SEQ ID NO: 28; (iii) The nucleotide sequence of allele r is identical to SEQ ID NO: 28 except that the nucleotide sequence of allele r comprises a GTC codon instead of an ATC codon at the position labelled “I474V” in SEQ ID NO: 28; and a GGG codon instead of an GAG codon at the position labelled “E670G” in SEQ ID NO: 28; (iv) The nucleotide sequence of allele p is identical to SEQ ID NO: 28 except that the nucleotide sequence of allele p comprises a GTC codon instead of a GCC codon at the position labelled “A53V” in SEQ ID NO: 28; and a GTC codon instead of an ATC codon at the position labelled “I474V” in SEQ ID NO: 28; (v) The nucleotide sequence of allele m is identical to SEQ ID NO: 28 except that the nucleotide sequence of allele m comprises a ACC codon instead of a GCC codon at the position labelled “A443T” in SEQ ID NO: 28; (vi) The nucleotide sequence of allele e is identical to SEQ ID NO: 28 except that the nucleotide sequence of allele e comprises a AGT codon instead of an AAT codon at the position labelled “N425S” in SEQ ID NO: 28; and a GTC codon instead of an ATC codon at the position labelled “I474V” in SEQ ID NO: 28; (vii) The nucleotide sequence of allele h is identical to SEQ ID NO: 28 except that the nucleotide sequence of allele h comprises a ACC codon instead of a GCC codon at the position labelled “A443T” in SEQ ID NO: 28; and a CCG codon instead of a CAG codon at the position labelled “Q619P” in SEQ ID NO: 28; (viii) The nucleotide sequence of allele aj is identical to SEQ ID NO: 28 except that the nucleotide sequence of allele aj comprises a CTT codon instead of an CGT codon at the position labelled “R46L” in SEQ ID NO: 28; and a GTC codon instead of an ATC codon at the position labelled “I474V” in SEQ ID NO: 28; and (ix) The nucleotide sequence of allele q is identical to SEQ ID NO: 28 except that the nucleotide sequence of allele q comprises a GTC codon instead of a GCC codon at the position labelled “A53V” in SEQ ID NO: 28; and a GGG codon instead of an GAG codon at the position labelled “E670G” in SEQ ID NO: 28.Variant Pro-Form Amino Acid Sequences (Numbering is as per SEQ ID NO: 1 recited above) (A) The amino acid sequence of form f is identical to the amino acid sequence from amino acid number 31 to (and including) amino acid number 692 of SEQ ID NO: 1 except that the amino acid sequence of form f comprises a valine at position 474; (B) The amino acid sequence of form c is identical to the amino acid sequence from amino acid number 31 to (and including) amino acid number 692 of SEQ ID NO: 1 except that the amino acid sequence of form c comprises a glycine at position 670; (C) The amino acid sequence of form r is identical to the amino acid sequence from amino acid number 31 to (and including) amino acid number 692 of SEQ ID NO: 1 except that the amino acid sequence of form r comprises a valine at position 474 and a glycine at position 670; (D) The amino acid sequence of form p is identical the amino acid sequence from amino acid number 31 to (and including) amino acid number 692 of SEQ ID NO: 1 except that the amino acid sequence of form p comprises a valine at position 53 and a valine at position 474; (E) The amino acid sequence of form m is identical to the amino acid sequence from amino acid number 31 to (and including) amino acid number 692 of SEQ ID NO: 1 except that the amino acid sequence of form m comprises a threonine at position 443; (F) The amino acid sequence of form e is identical to the amino acid sequence from amino acid number 31 to (and including) amino acid number 692 of SEQ ID NO: 1 except that the amino acid sequence of form e comprises a serine at position 425 and a valine at position 474; (G) The amino acid sequence of form h is identical to the amino acid sequence from amino acid number 31 to (and including) amino acid number 692 of SEQ ID NO: 1 except that the amino acid sequence of form h comprises a threonine at position 443 and a proline at position 619; (H) The amino acid sequence of form aj is identical to the amino acid sequence from amino acid number 31 to (and including) amino acid number 692 of SEQ ID NO: 1 except that the amino acid sequence of form aj comprises a leucine at position 46 and a valine at position 474; and (I) The amino acid sequence of form q is identical to the amino acid sequence from amino acid number 31 to (and including) amino acid number 692 of SEQ ID NO: 1 except that the amino acid sequence of form q comprises a valine at position 53 and a glycine at position 670.Variant Mature Form Amino Acid Sequences (Numbering is as per SEQ ID NO: 1 recited above) (A′) The amino acid sequence of form f is identical to SEQ ID NO: 2 except that the amino acid sequence of form f comprises a valine at position 474; (B′) The amino acid sequence of form c is identical to SEQ ID NO: 2 except that the amino acid sequence of form c comprises a glycine at position 670; (C′) The amino acid sequence of form r is identical to SEQ ID NO: 2 except that the amino acid sequence of form r comprises a valine at position 474 and a glycine at position 670; (D′) The amino acid sequence of form p is identical to SEQ ID NO: 2 except that the amino acid sequence of form p comprises a valine at position 474; (E′) The amino acid sequence of form m is identical to SEQ ID NO: 2 except that the amino acid sequence of form m comprises a threonine at position 443; (F′) The amino acid sequence of form e is identical to SEQ ID NO: 2 except that the amino acid sequence of form e comprises a serine at position 425 and a valine at position 474; (G′) The amino acid sequence of form h is identical to SEQ ID NO: 2 except that the amino acid sequence of form h comprises a threonine at position 443 and a proline at position 619; (H′) The amino acid sequence of form aj is identical to SEQ ID NO: 2 except that the amino acid sequence of form aj comprises valine at position 474; and (I′) The amino acid sequence of form q is identical to SEQ ID NO: 2 except that the amino acid sequence of form q comprises a glycine at position 670.The mature form of p is identical to the mature form off and aj.","The mature form of c is identical to the mature form of q.","Further sequence analysis and 3D in silico modelling (see FIG.","1) revealed that selected variants also fulfilled the following selection criteria:— PCSK9 variants whose variant amino acid residues (versus the common form of human PCSK9) are found in the mature form of the target (ie, outside the pro-domain); and PCSK9 variants whose variant amino acid residues (versus the common form of human PCSK9) are surface-exposed on the target, which the inventor saw as contributing to determining the topography of the target and potentially contributing to how and where ligand binding on the target occurs.","As shown in FIG.","1, identified positions 425, 443, 474, 619 and 670 (found in the selected variants of the invention) are all surface-exposed and outside of the pro-domain.","Variant positions 425 and 443 are surface-exposed on the catalytic domain, while variant positions 474, 619 and 670 are surface-exposed on the C-terminal domain.","In a first example, the invention addresses the need to treat humans having naturally-occurring rarer natural PCSK9 alleles, genotypes and phenotypes (rarer protein forms).","In this respect, the invention provides the following aspects: In a First Aspect: An anti-human PCSK9 ligand for use in a method of treating and/or preventing a PCSK9-mediated disease or condition in a human whose genome comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37, wherein the method comprises administering the ligand to the human.","In an example, the nucleotide sequence is selected from the group consisting of SEQ ID NOs: 29-35 and 37; or selected from the group consisting of SEQ ID NOs: 29-32 and 34-37; or selected from the group consisting of SEQ ID NOs: 29-32, 34, 35 and 37.These are naturally-occurring allele (haplotype) sequences that do not encode 46L and which meet the criteria set out above.","These groups comprise variants that are associated with elevated LDL-C.","In an example, the nucleotide sequence is SEQ ID NO: 34, that encodes a 425S, which is associated with elevated LDL-C (Pisciotta et al 2006).","In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31 and 37, that encode 670G which is a marker for severity of coronary atherosclerosis (Chen et al 2005).","In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35, 36 and 37; or selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35 and 37.These are allele (haplotype) sequences that have a naturally-occurring combination of differences from SEQ ID NO: 28 (form a) and which meet the criteria set out above.","In an example, the nucleotide sequence is SEQ ID NO: 29.In an example, the nucleotide sequence is SEQ ID NO: 30.In an example, the nucleotide sequence is SEQ ID NO: 31.In an example, the nucleotide sequence is SEQ ID NO: 32.In an example, the nucleotide sequence is SEQ ID NO: 33.In an example, the nucleotide sequence is SEQ ID NO: 34.In an example, the nucleotide sequence is SEQ ID NO: 35.In an example, the nucleotide sequence is SEQ ID NO: 36.In an example, the nucleotide sequence is SEQ ID NO: 37.In a Second Aspect: The ligand of aspect 1, wherein the ligand has been or is determined as capable of binding a human PCSK9 selected from the group consisting forms f, c, r, p, m, e, h, aj and q.","In an example of any aspect, the ligand binds (or has been determined to bind) two, three, four or more human PCSK9 selected from the group consisting forms f, c, r, p, m, e, h, aj and q.","In an example of any aspect, the ligand comprises a protein domain that specifically binds to PCSK9, eg, a human PCSK9 selected from the group consisting forms f, c, r, p, m, e, h, aj and q.","The term “specifically binds,” or the like, means that a ligand, eg, an antibody or antigen-binding fragment thereof, forms a complex with an antigen that is relatively stable under physiologic conditions.","Specific binding can be characterized by an equilibrium dissociation constant of at least about 1×10−6 M or less (e.g., a smaller KD denotes a tighter binding).","Methods for determining whether two molecules specifically bind are well known in the art and include, for example, equilibrium dialysis, surface plasmon resonance, and the like.","An isolated antibody that specifically binds a human PCSK9 may, however, exhibit cross-reactivity to other antigens such as a PCSK9 molecule from another specie.","Moreover, multi-specific antibodies (e.g., bispecifics) that bind to human PCSK9 and one or more additional antigens are nonetheless considered antibodies that “specifically bind” PCSK9, as used herein.","In an example of any aspect, the ligand comprises or consists of a protein that mimics the EGFA domain of the LDL receptor and specifically binds to PCSK9, eg, a human PCSK9 selected from the group consisting forms f, c, r, p, m, e, h, aj and q.","In an example of any aspect, the ligand antagonises PCSK9, eg, a human PCSK9 selected from the group consisting forms f, c, r, p, m, e, h, aj and q.","In an example of any aspect, the method comprises (before administering the ligand) the step of determining that the ligand is capable of binding a human PCSK9 selected from the group consisting forms f, c, r, p, m, e, h, aj and q.","In an example of any aspect, binding is determined by SPR.","In an example of any aspect, binding is determined by ELISA.","In an example of any aspect, said forms are the mature forms.","In an example of any aspect, said forms are the pro-forms.","In a Third Aspect: A ligand that binds a human PCSK9 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 4-27 for use in a method comprising the step of using the ligand to target said PCSK9 in a human to treat and/or prevent a disease or condition mediated by PCSK9, the method comprising administering the ligand to the human.","In an example, the disease or condition is mediated by a human PCSK9 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 4-27.In an example, the amino acid sequence selected from the group consisting of SEQ ID NOs: 4-23, 26 and 27; or selected from the group consisting of SEQ ID NOs: 4-14 and 18-27; or selected from the group consisting of SEQ ID NOs: 4-14, 18-23, 26 and 27.These are naturally-occurring sequences that do not comprise 46L and which meet the criteria set out above.","These groups comprise variants that are associated with elevated LDL-C.","In an example, the amino acid sequence is SEQ ID NO: 18, 19 or 20, that comprises a 425S, which is associated with elevated LDL-C (Pisciotta et al 2006).","In an example, the amino acid sequence selected from the group consisting of SEQ ID NOs: 10, 11, 12, 26 and 27, that comprise 670G which is a marker for severity of coronary atherosclerosis (Chen et al 2005).","In an example, the amino acid sequence selected from the group consisting of SEQ ID NOs: 10-14 and 18-27; or selected from the group consisting of SEQ ID NOs: 10-14, 18-23, 26 and 27.These are sequences that have a naturally-occurring combination of differences from SEQ ID NOs: 1-3 (form a) and which meet the criteria set out above.","In an example, the amino acid sequence is SEQ ID NO: 4.In an example, the amino acid sequence is SEQ ID NO: 5.In an example, the amino acid sequence is SEQ ID NO: 6.In an example, the amino acid sequence is SEQ ID NO: 7.In an example, the amino acid sequence is SEQ ID NO: 8.In an example, the amino acid sequence is SEQ ID NO: 9.In an example, the amino acid sequence is SEQ ID NO: 10.In an example, the amino acid sequence is SEQ ID NO: 11.In an example, the amino acid sequence is SEQ ID NO: 12.In an example, the amino acid sequence is SEQ ID NO: 13.In an example, the amino acid sequence is SEQ ID NO: 14.In an example, the amino acid sequence is SEQ ID NO: 15.In an example, the amino acid sequence is SEQ ID NO: 16.In an example, the amino acid sequence is SEQ ID NO: 17.In an example, the amino acid sequence is SEQ ID NO: 18.In an example, the amino acid sequence is SEQ ID NO: 19.In an example, the amino acid sequence is SEQ ID NO: 20.In an example, the amino acid sequence is SEQ ID NO: 21.In an example, the amino acid sequence is SEQ ID NO: 22.In an example, the amino acid sequence is SEQ ID NO: 23.In an example, the amino acid sequence is SEQ ID NO: 24.In an example, the amino acid sequence is SEQ ID NO: 25.In an example, the amino acid sequence is SEQ ID NO: 26.In an example, the amino acid sequence is SEQ ID NO: 27.In a Fourth Aspect: The ligand of aspect 3, wherein the genome of the human comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37.In an example, the nucleotide sequence is selected from the group consisting of SEQ ID NOs: 29-35 and 37; or selected from the group consisting of SEQ ID NOs: 29-32 and 34-37; or selected from the group consisting of SEQ ID NOs: 29-32, 34, 35 and 37.These are naturally-occurring allele (haplotype) sequences that do not encode 46L and which meet the criteria set out above.","These groups comprise variants that are associated with elevated LDL-C.","In an example, the nucleotide sequence is SEQ ID NO: 34, that encodes a 425S, which is associated with elevated LDL-C (Pisciotta et al 2006).","In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31 and 37, that encode 670G which is a marker for severity of coronary atherosclerosis (Chen et al 2005).","In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35, 36 and 37; or selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35 and 37.These are allele (haplotype) sequences that have a naturally-occurring combination of differences from SEQ ID NO: 28 (form a) and which meet the criteria set out above.","In an example, the nucleotide sequence is SEQ ID NO: 29 In an example, the nucleotide sequence is SEQ ID NO: 30.In an example, the nucleotide sequence is SEQ ID NO: 31.In an example, the nucleotide sequence is SEQ ID NO: 32.In an example, the nucleotide sequence is SEQ ID NO: 33 In an example, the nucleotide sequence is SEQ ID NO: 34 In an example, the nucleotide sequence is SEQ ID NO: 35.In an example, the nucleotide sequence is SEQ ID NO: 36.In an example, the nucleotide sequence is SEQ ID NO: 37.In a Fifth Aspect: The ligand of any preceding aspect, wherein the human has been or is genotyped as positive for a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof.","In an example, the nucleotide sequence is selected from the group consisting of SEQ ID NOs: 29-35 and 37; or selected from the group consisting of SEQ ID NOs: 29-32 and 34-37; or selected from the group consisting of SEQ ID NOs: 29-32, 34, 35 and 37.These are naturally-occurring allele (haplotype) sequences that do not encode 46L and which meet the criteria set out above.","These groups comprise variants that are associated with elevated LDL-C.","In an example, the nucleotide sequence is SEQ ID NO: 34, that encodes a 425S, which is associated with elevated LDL-C (Pisciotta et al 2006).","In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31 and 37, that encode 670G which is a marker for severity of coronary atherosclerosis (Chen et al 2005).","In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35, 36 and 37; or selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35 and 37.These are allele (haplotype) sequences that have a naturally-occurring combination of differences from SEQ ID NO: 28 (form a) and which meet the criteria set out above.","In an example, the nucleotide sequence is SEQ ID NO: 29.In an example, the nucleotide sequence is SEQ ID NO: 30.In an example, the nucleotide sequence is SEQ ID NO: 31.In an example, the nucleotide sequence is SEQ ID NO: 32.In an example, the nucleotide sequence is SEQ ID NO: 33.In an example, the nucleotide sequence is SEQ ID NO: 34.In an example, the nucleotide sequence is SEQ ID NO: 35.In an example, the nucleotide sequence is SEQ ID NO: 36.In an example, the nucleotide sequence is SEQ ID NO: 37.In a Sixth Aspect: The ligand of any preceding aspect, wherein the human has been or is phenotyped as positive for a human PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q or at least the catalytic or C-terminal domain thereof.","In an example, said forms are the mature forms.","In an example, said forms are the pro-forms.","In a Seventh Aspect: The ligand of any preceding aspect, wherein the method comprises genotyping the human as positive for a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof.","In an example, the nucleotide sequence is selected from the group consisting of SEQ ID NOs: 29-35 and 37; or selected from the group consisting of SEQ ID NOs: 29-32 and 34-37; or selected from the group consisting of SEQ ID NOs: 29-32, 34, 35 and 37.These are naturally-occurring allele (haplotype) sequences that do not encode 46L and which meet the criteria set out above.","These groups comprise variants that are associated with elevated LDL-C.","In an example, the nucleotide sequence is SEQ ID NO: 34, that encodes a 425S, which is associated with elevated LDL-C (Pisciotta et al 2006).","In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31 and 37, that encode 670G which is a marker for severity of coronary atherosclerosis (Chen et al 2005).","In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35, 36 and 37; or selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35 and 37.These are allele (haplotype) sequences that have a naturally-occurring combination of differences from SEQ ID NO: 28 (form a) and which meet the criteria set out above.","In an example, the nucleotide sequence is SEQ ID NO: 29.In an example, the nucleotide sequence is SEQ ID NO: 30.In an example, the nucleotide sequence is SEQ ID NO: 31.In an example, the nucleotide sequence is SEQ ID NO: 32.In an example, the nucleotide sequence is SEQ ID NO: 33.In an example, the nucleotide sequence is SEQ ID NO: 34.In an example, the nucleotide sequence is SEQ ID NO: 35.In an example, the nucleotide sequence is SEQ ID NO: 36.In an example, the nucleotide sequence is SEQ ID NO: 37.In an Eighth Aspect: The ligand of any preceding aspect, wherein the method comprises phenotyping the human has positive for a human PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q or at least the catalytic or C-terminal domain thereof.","In an example, said forms are the mature forms.","In an example, said forms are the pro-forms.","In a Ninth Aspect: The ligand of any preceding aspect, wherein the human has been or is genotyped as heterozygous for a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof, optionally wherein the human has been or is genotyped as comprising the nucleotide sequence of SEQ ID NO: 28 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof and a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof.","“Heterozygous” here means that in the human's genotype one allele comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof and other allele can be any PCSK9 (eg, form a, a′ or an allele comprising a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof).","In an example, the method comprises (before administering the ligand) genotyping the human as heterozygous for a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof, optionally also genotyping the human as comprising the nucleotide sequence of SEQ ID NO: 28 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof and a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof.","In an example, the nucleotide sequence is selected from the group consisting of SEQ ID NOs: 29-35 and 37; or selected from the group consisting of SEQ ID NOs: 29-32 and 34-37; or selected from the group consisting of SEQ ID NOs: 29-32, 34, 35 and 37.These are naturally-occurring allele (haplotype) sequences that do not encode 46L and which meet the criteria set out above.","These groups comprise variants that are associated with elevated LDL-C.","In an example, the nucleotide sequence is SEQ ID NO: 34, that encodes a 425S, which is associated with elevated LDL-C (Pisciotta et al 2006).","In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31 and 37, that encode 670G which is a marker for severity of coronary atherosclerosis (Chen et al 2005).","In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35, 36 and 37; or selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35 and 37.These are allele (haplotype) sequences that have a naturally-occurring combination of differences from SEQ ID NO: 28 (form a) and which meet the criteria set out above.","In an example, the nucleotide sequence is SEQ ID NO: 29.In an example, the nucleotide sequence is SEQ ID NO: 30.In an example, the nucleotide sequence is SEQ ID NO: 31.In an example, the nucleotide sequence is SEQ ID NO: 32.In an example, the nucleotide sequence is SEQ ID NO: 33.In an example, the nucleotide sequence is SEQ ID NO: 34.In an example, the nucleotide sequence is SEQ ID NO: 35.In an example, the nucleotide sequence is SEQ ID NO: 36.In an example, the nucleotide sequence is SEQ ID NO: 37.In a Tenth Aspect: The ligand of any one of aspects 1 to 9, wherein the genome of the human has been or is genotyped as homozygous for a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof.","“Homozygous” here means that in the human's genotype each allele comprises the same nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof.","In an example, the method comprises genotyping the human as homozygous for a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof.","In an example, the nucleotide sequence is selected from the group consisting of SEQ ID NOs: 29-35 and 37; or selected from the group consisting of SEQ ID NOs: 29-32 and 34-37; or selected from the group consisting of SEQ ID NOs: 29-32, 34, 35 and 37.These are naturally-occurring allele (haplotype) sequences that do not encode 46L and which meet the criteria set out above.","These groups comprise variants that are associated with elevated LDL-C.","In an example, the nucleotide sequence is SEQ ID NO: 34, that encodes a 425S, which is associated with elevated LDL-C (Pisciotta et al 2006).","In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31 and 37, that encode 670G which is a marker for severity of coronary atherosclerosis (Chen et al 2005).","In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35, 36 and 37; or selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35 and 37.These are allele (haplotype) sequences that have a naturally-occurring combination of differences from SEQ ID NO: 28 (form a) and which meet the criteria set out above.","In an example, the nucleotide sequence is SEQ ID NO: 29.In an example, the nucleotide sequence is SEQ ID NO: 30.In an example, the nucleotide sequence is SEQ ID NO: 31.In an example, the nucleotide sequence is SEQ ID NO: 32.In an example, the nucleotide sequence is SEQ ID NO: 33.In an example, the nucleotide sequence is SEQ ID NO: 34.In an example, the nucleotide sequence is SEQ ID NO: 35.In an example, the nucleotide sequence is SEQ ID NO: 36.In an example, the nucleotide sequence is SEQ ID NO: 37.In an Eleventh Aspect: The ligand of any preceding aspect, wherein the ligand comprises an antibody binding site that binds a human PCSK9 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 4-27 and optionally has been or is determined as capable of such binding.","In an example, the method comprises (before administering the ligand) the step of determining that the ligand is capable of binding to said human PCSK9.In an example, the binding is specific binding.","In an example, the ligand binds (or has been determined as binding) to the PCSK9 with an affinity (Kd) of 1 mM, 100 nM, 10 nM or 1 nM or less.","In an embodiment, the affinity is no less than 10, 100 or 1000 fM.","In an example, binding or affinity is determined by SPR or ELISA.","In an example, the disease or condition is mediated by a human PCSK9 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 4-27.In an example, the amino acid sequence selected from the group consisting of SEQ ID NOs: 4-23, 26 and 27; or selected from the group consisting of SEQ ID NOs: 4-14 and 18-27; or selected from the group consisting of SEQ ID NOs: 4-14, 18-23, 26 and 27.These are naturally-occurring sequences that do not comprise 46L and which meet the criteria set out above.","These groups comprise variants that are associated with elevated LDL-C.","In an example, the amino acid sequence is SEQ ID NO: 18, 19 or 20, that comprises a 425S, which is associated with elevated LDL-C (Pisciotta et al 2006).","In an example, the amino acid sequence selected from the group consisting of SEQ ID NOs: 10, 11, 12, 26 and 27, that comprise 670G which is a marker for severity of coronary atherosclerosis (Chen et al 2005).","In an example, the amino acid sequence selected from the group consisting of SEQ ID NOs: 10-14 and 18-27; or selected from the group consisting of SEQ ID NOs: 10-14, 18-23, 26 and 27.These are sequences that have a naturally-occurring combination of differences from SEQ ID NOs: 1-3 (form a) and which meet the criteria set out above In an example, the amino acid sequence is SEQ ID NO: 4.In an example, the amino acid sequence is SEQ ID NO: 5.In an example, the amino acid sequence is SEQ ID NO: 6.In an example, the amino acid sequence is SEQ ID NO: 7.In an example, the amino acid sequence is SEQ ID NO: 8.In an example, the amino acid sequence is SEQ ID NO: 9.In an example, the amino acid sequence is SEQ ID NO: 10.In an example, the amino acid sequence is SEQ ID NO: 11.In an example, the amino acid sequence is SEQ ID NO: 12.In an example, the amino acid sequence is SEQ ID NO: 13.In an example, the amino acid sequence is SEQ ID NO: 14.In an example, the amino acid sequence is SEQ ID NO: 15.In an example, the amino acid sequence is SEQ ID NO: 16.In an example, the amino acid sequence is SEQ ID NO: 17.In an example, the amino acid sequence is SEQ ID NO: 18.In an example, the amino acid sequence is SEQ ID NO: 19.In an example, the amino acid sequence is SEQ ID NO: 20.In an example, the amino acid sequence is SEQ ID NO: 21.In an example, the amino acid sequence is SEQ ID NO: 22.In an example, the amino acid sequence is SEQ ID NO: 23.In an example, the amino acid sequence is SEQ ID NO: 24.In an example, the amino acid sequence is SEQ ID NO: 25.In an example, the amino acid sequence is SEQ ID NO: 26.In an example, the amino acid sequence is SEQ ID NO: 27.In a Twelfth Aspect: The ligand of aspect 11, wherein the ligand is an antibody or antibody fragment.","For example, the antibody or antibody fragment is a PCSK9 antagonist, eg, neutralises PCSK9.Examples of such antibodies are disclosed, for instance, in WO 2008/057457, WO2008/057458, WO 2008/057459, WO 2008/063382, WO 2008/133647, WO 2009/100297, WO 2009/100318, WO 2011/037791, WO 2011/053759, WO 2011/053783, WO 2008/125623, WO 2011/072263, WO 2009/055783, WO 2010/029513, WO 2011/111007, WO 2010/077854, the disclosures and sequences of such antibodies being incorporated herein for use in the invention in their entireties by reference.","One specific example is AMG 145 (Amgen), LY3015014 (Eli Lilly) or alirocumab.","Advantageously, the ligand is or comprises alirocumab.","Alternatively, the ligand is or comprises evolocumab.","In an example, the ligand is SAR236553/REGN727 (Sanofi Aventis/Regeneron) or a PCSK9-binding derivative thereof.","In an example, the ligand comprises or consists of a neutralizing antibody that binds to the PCSK9, wherein the antibody binds to PCSK9 and reduces the likelihood that PCSK9 binds to LDLR.","The ligand of aspect 11, wherein the ligand is a PCSK9 antagonist, eg, neutralises PCSK9.In an example of any aspect of the invention, the ligand comprises or consists a ligand selected from evolocumab, 1D05-IgG2 (Merck & Co.), ALN-PCS02 (Alnylam), RN316 (Pfizer-Rinat), LY3015014 (Eli Lilly) and alirocumab (SAR236553/REGN727; Sanofi Aventis/Regeneron).","In Thirteenth Aspect: The ligand of any one of aspects 1 to 10, wherein (i) the ligand comprises a sequence of contiguous nucleotides that specifically hybridises to a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof, or specifically hybridises to an antisense sequence or an RNA transcript of said sequence, wherein said sequence of contiguous nucleotides hybridises to at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 or hybridises to an antisense sequence or an RNA transcript thereof respectively; and/or (ii) the ligand comprises a sequence of at least 10 contiguous nucleotides of a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or is an antisense sequence or RNA version of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28.In an example, the nucleotide sequence is selected from the group consisting of SEQ ID NOs: 29-35 and 37; or selected from the group consisting of SEQ ID NOs: 29-32 and 34-37; or selected from the group consisting of SEQ ID NOs: 29-32, 34, 35 and 37.These are naturally-occurring allele (haplotype) sequences that do not encode 46L and which meet the criteria set out above.","These groups comprise variants that are associated with elevated LDL-C.","In an example, the nucleotide sequence is SEQ ID NO: 34, that encodes a 425S, which is associated with elevated LDL-C (Pisciotta et al 2006).","In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31 and 37, that encode 670G which is a marker for severity of coronary atherosclerosis (Chen et al 2005).","In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35, 36 and 37; or selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35 and 37.These are allele (haplotype) sequences that have a naturally-occurring combination of differences from SEQ ID NO: 28 (form a) and which meet the criteria set out above.","In an example, the nucleotide sequence is SEQ ID NO: 29.In an example, the nucleotide sequence is SEQ ID NO: 30.In an example, the nucleotide sequence is SEQ ID NO: 31.In an example, the nucleotide sequence is SEQ ID NO: 32.In an example, the nucleotide sequence is SEQ ID NO: 33.In an example, the nucleotide sequence is SEQ ID NO: 34.In an example, the nucleotide sequence is SEQ ID NO: 35.In an example, the nucleotide sequence is SEQ ID NO: 36.In an example, the nucleotide sequence is SEQ ID NO: 37.In an embodiment, the ligand comprises at least 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 50 or 100 contiguous nucleotides of said nucleotide sequence.","In a Fourteenth Aspect: The ligand of any preceding aspect, wherein said disease or condition is hyperlipidaemia, hypercholesterolaemia (eg, familial hypercholesterolaemia), heart attack, stroke, coronary heart disease, atherosclerosis or a cardiovascular disease or condition.","The ligand of any preceding aspect, wherein the disease or condition is hypercholesterolemia, hyperlipidemia, hypercholesterolemia, dyslipidemia, cholestatic liver disease, nephrotic syndrome, hypothyroidism, obesity, atherosclerosis or a cardiovascular disease.","In an example, said disease or condition is hypercholesterolaemia.","The term “hypercholesterolaemia,” as used herein, refers to a condition in which cholesterol levels are elevated above a desired level.","In some embodiments, this denotes that serum cholesterol levels are elevated.","In some embodiments, the desired level takes into account various “risk factors” that are known to one of skill in the art (and are described or referenced in US20120093818).","The ligand of any preceding aspect, wherein the human is identified as heterozygous for Familial Hypercholesterolemia, statin intolerant, statin uncontrolled, or at risk for developing hypercholesterolemia, dyslipidemia, cholestatic liver disease, nephrotic syndrome, hypothyroidism, obesity, atherosclerosis or a cardiovascular disease.","In a Fifteenth Aspect: The ligand of any preceding aspect, wherein said disease or condition is associated with elevated LDL cholesterol.","Cholesterol levels are measured in milligrams (mg) of cholesterol per deciliter (dL) of blood in the United States and some other countries.","Canada and most European countries measure cholesterol in millimoles (mmol) per liter (L) of blood.","Below are general guideline ideal ranges and elevated ranges.","Total cholesterol* Total cholesterol (Canada and (U.S. and some other countries) most of Europe) Below 200 mg/dL Below 5.2 mmol/L Ideal 200-239 mg/dL 5.2-6.2 mmol/L Borderline high 240 mg/dL and above Above 6.2 mmol/L High LDL cholesterol* LDL cholesterol (Canada and (U.S. and some other countries) most of Europe) 100-129 mg/dL 2.6-3.3 mmol/L Ideal 130-159 mg/dL 3.4-4.1 mmol/L Borderline high 160-189 mg/dL 4.1-4.9 mmol/L High 190 mg/dL and above Above 4.9 mmol/L Very high *Canadian and European guidelines differ slightly from U.S. guidelines.","These conversions are based on U.S. guidelines.","Elevated LDL cholesterol is, therefore, 160 mg/dL or above (4.1 mmol/L or above).","In a Sixteenth Aspect: The ligand of any preceding aspect, wherein the ligand inhibits human PCSK9 binding to human LDL receptor and optionally has been or is determined as capable of such inhibition.","In an example, the method comprises (before administering the ligand) determining that the ligand is capable of such inhibition.","Inhibition determination is eg, inhibition in a blood or serum sample, at rtp, at ph7, at 37 degrees centigrade and/or under the physiological conditions of a human body.","In a Seventeenth Aspect: The ligand of any preceding aspect, wherein the human is resistant or substantially resistant to statin (eg, avorstatin and/or fluvastatin) treatment of said disease or condition.","In an Eighteenth Aspect: The ligand of any preceding aspect, wherein the ligand is for treating and/or preventing a PCSK9-mediated disease or condition in a human (i) whose genome comprises SEQ ID NO: 29 and wherein the human is of ASW, YRI, GBR, TSI, CLM, LWK, MXL, JPT, PUR, IBS, FIN or CEU ancestry; or (ii) whose genome comprises SEQ ID NO: 30 and wherein the human is of ASW, YRI, GBR, TSI, CLM, CHB, LWK, CHS, JPT, PUR, FIN or CEU ancestry; or (iii) whose genome comprises SEQ ID NO: 32 and wherein the human is of ASW, GBR, TSI, CLM, JPT, PUR, IBS, FIN or CEU ancestry; or (iv) whose genome comprises SEQ ID NO: 33 and wherein the human is of LWK, ASW, YRI or CLM ancestry; or (v) whose genome comprises SEQ ID NO: 34 and wherein the human is of LWK, ASW or YRI ancestry; or (vi) whose genome comprises SEQ ID NO: 35 and wherein the human is of PUR, TSI, FIN or CEU ancestry; or (vii) whose genome comprises SEQ ID NO: 36 and wherein the human is of LWK, ASW or YRI ancestry; or (viii) whose genome comprises SEQ ID NO: 37 and wherein the human is of CHS, ASW, JPT, PUR or CHB ancestry.","In a Ninteenth Aspect: The ligand of any preceding aspect, wherein the ligand is for treating and/or preventing a PCSK9-mediated disease or condition in a human (i) that expresses PCSK9 form f and wherein the human is of ASW, YRI, GBR, TSI, CLM, LWK, MXL, JPT, PUR, IBS, FIN or CEU ancestry; or (ii) that expresses PCSK9 form c and wherein the human is of ASW, YRI, GBR, TSI, CLM, CHB, LWK, CHS, JPT, PUR, FIN or CEU ancestry; or (iii) that expresses PCSK9 form p and wherein the human is of ASW, GBR, TSI, CLM, JPT, PUR, IBS, FIN or CEU ancestry; or (iv) that expresses PCSK9 form m and wherein the human is of LWK, ASW, YRI or CLM ancestry; or (v) that expresses PCSK9 form e and wherein the human is of LWK, ASW or YRI ancestry; or (vi) that expresses PCSK9 form h and wherein the human is of PUR, TSI, FIN or CEU ancestry; or (vii) that expresses PCSK9 form aj and wherein the human is of LWK, ASW or YRI ancestry; or (viii) that expresses PCSK9 form q and wherein the human is of CHS, ASW, JPT, PUR or CHB ancestry.","In an example, said forms are the mature forms.","In an example, said forms are the pro-forms.","In a Twentieth Aspect: A pharmaceutical composition or kit for treating and/or preventing a PCSK9-mediated condition or disease (eg, as recited in aspect 14 or 15), the composition or kit comprising a ligand of any preceding aspect and optionally a statin (eg, cerovastatin, atorvastatin, simvastatin, pitavastin, rosuvastatin, fluvastatin, lovastatin or pravastatin); and optionally in combination with a label or instructions for use to treat and/or prevent said disease or condition in a human (eg, covering treatment of a human as recited in aspect 18 or 19); optionally wherein the label or instructions comprise a marketing authorisation number (eg, an FDA or EMA authorisation number); optionally wherein the label or instructions comprise directions to administer alirocumab or evolocumab to said human; optionally wherein the kit comprises an IV or injection device that comprises the ligand (and, eg, also a statin).","In a Twenty-first Aspect: A method of producing an anti-human PCSK9 antibody binding site, the method comprising obtaining a plurality of anti-PCSK9 antibody binding sites, screening the antibody binding sites for binding to a human PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q or a catalytic or C-terminal domain or a peptide thereof that comprises amino acid variation from the corresponding sequence of SEQ ID NO: 1, 2 or 3 and isolating an antibody binding site that binds in the screening step, and optionally producing a form f c, r, p, m, e, h, aj or q PCSK9-binding fragment or derivative of the isolated antibody.","In an example, said forms are the mature forms.","In an example, said forms are the pro-forms.","In an example of this and the next aspect, the plurality of binding sites comprises or consists of a plurality of 4-chain antibodies or fragments thereof, eg, dAbs, Fabs or scFvs.","Suitable methods for producing pluralities of binding sites for screening include phage display (producing a phage display library of antibody binding sites), ribosome display (producing a ribosome display library of antibody binding sites), yeast display (producing a yeast display library of antibody binding sites), or immunisation of a non-human vertebrate (eg, a rodent, eg, a mouse or rat, eg, a Velocimouse™, Kymouse™, Xenomouse™, Aliva Mouse™, HuMab Mouse™, Omnimouse™ Omnirat™ or MeMo Mouse™) with a PCSK9 epitope and isolation of a repertoire of antibody-producing cells (eg, a B-cell, plasma cell or plasmablast repertoire) and/or a repertoire of isolated antibodies.","In an example, the method comprises selecting one or more antibody binding sites that each specifically binds to a human PCSK9 epitope comprising amino acid variation from the corresponding sequence of SEQ ID NO: 1, 2 or 3.In a Twenty-Second Aspect: A method of producing an anti-human PCSK9 antibody, the method comprising immunising a non-human vertebrate (eg, a mouse or a rat) with a human PCSK9 comprising an amino acid sequence selected from the group consisting of the amino acid sequences of forms f, c, r, p, m, e, h, aj and q or a catalytic or C-terminal domain or a peptide thereof that comprises amino acid variation from the corresponding sequence of SEQ ID NO: 1, 2 or 3 and isolating an antibody that binds a human PCSK9 comprising selected from the group consisting of forms f, c, r, p, m, e, h, aj and q or a catalytic or C-terminal domain or a peptide thereof that comprises amino acid variation from the corresponding sequence of SEQ ID NO: 1, 2 or 3, and optionally producing a form f, c, r, p, m, e, h, aj or q PCSK9-binding fragment or derivative of the isolated antibody.","In an example, said forms are the mature forms.","In an example, said forms are the pro-forms.","In a Twenty-third Aspect: The method of aspect 21 or 22, comprising the step of obtaining a nucleic acid encoding the antibody, fragment, derivative or binding site and optionally inserting the nucleic acid in an expression vector.","For example, the method comprises isolating a cell (eg, B-cell, plasmablast, plasma cell or memory cell) comprising the nucleic acid, wherein the cell is obtained from a non-human vertebrate that has been immunised with the PCSK9 epitope.","In a Twenty-fourth Aspect: A kit for PCSK9 genotyping a human, wherein the kit comprises a nucleic acid (i) comprising a sequence of 10 or more (eg, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100 or more) contiguous nucleotides that specifically hybridises to a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof, or specifically hybridises to an antisense sequence or an RNA transcript of said sequence, wherein said sequence of contiguous nucleotides hybridises to at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 or hybridises to an antisense sequence or an RNA transcript thereof, and/or (ii) comprising a sequence of at least 10 or more (eg, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100 or more) nucleotides of a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or comprising an antisense sequence or RNA version of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28.In an example, the nucleotide sequence is selected from the group consisting of SEQ ID NOs: 29-35 and 37; or selected from the group consisting of SEQ ID NOs: 29-32 and 34-37; or selected from the group consisting of SEQ ID NOs: 29-32, 34, 35 and 37.These are naturally-occurring allele (haplotype) sequences that do not encode 46L and which meet the criteria set out above.","These groups comprise variants that are associated with elevated LDL-C.","In an example, the nucleotide sequence is SEQ ID NO: 34, that encodes a 425S, which is associated with elevated LDL-C (Pisciotta et al 2006).","In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31 and 37, that encode 670G which is a marker for severity of coronary atherosclerosis (Chen et al 2005).","In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35, 36 and 37; or selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35 and 37.These are allele (haplotype) sequences that have a naturally-occurring combination of differences from SEQ ID NO: 28 (form a) and which meet the criteria set out above.","In an example, the nucleotide sequence is SEQ ID NO: 29.In an example, the nucleotide sequence is SEQ ID NO: 30.In an example, the nucleotide sequence is SEQ ID NO: 31.In an example, the nucleotide sequence is SEQ ID NO: 32.In an example, the nucleotide sequence is SEQ ID NO: 33.In an example, the nucleotide sequence is SEQ ID NO: 34.In an example, the nucleotide sequence is SEQ ID NO: 35.In an example, the nucleotide sequence is SEQ ID NO: 36.In an example, the nucleotide sequence is SEQ ID NO: 37.In a Twenty-Fifth Aspect: A kit for PCSK9 genotyping or phenotyping a human, wherein the kit comprises a ligand according to any one of aspects 1 to 19 or an antibody, fragment or derivative produced by the method of any one of aspects 21 to 23.In a Twenty-Sixth Aspect: Use of an anti-PCSK9 ligand that binds a human PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q in the manufacture of a medicament for treating and/or preventing a PCSK9-mediated disease or condition in a human whose genome comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37, optionally for treating and/or preventing a PCSK9-mediated disease or condition in a human as recited in aspect 18 or 19.In an example, said forms are the mature forms.","In an example, said forms are the pro-forms.","In a Twenty-Seventh Aspect: Use of an anti-PCSK9 ligand that binds a human PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q in the manufacture of a medicament for targeting said PCSK9 in a human to treat and/or prevent a disease or condition mediated by PCSK9, optionally for targeting PCSK9 in a human as recited in aspect 18 or 19.In an example, said forms are the mature forms.","In an example, said forms are the pro-forms.","In an example, the nucleotide sequence is selected from the group consisting of SEQ ID NOs: 29-35 and 37; or selected from the group consisting of SEQ ID NOs: 29-32 and 34-37; or selected from the group consisting of SEQ ID NOs: 29-32, 34, 35 and 37.These are naturally-occurring allele (haplotype) sequences that do not encode 46L and which meet the criteria set out above.","These groups comprise variants that are associated with elevated LDL-C.","In an example, the nucleotide sequence is SEQ ID NO: 34, that encodes a 425S, which is associated with elevated LDL-C (Pisciotta et al 2006).","In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31 and 37, that encode 670G which is a marker for severity of coronary atherosclerosis (Chen et al 2005).","In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35, 36 and 37; or selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35 and 37.These are allele (haplotype) sequences that have a naturally-occurring combination of differences from SEQ ID NO: 28 (form a) and which meet the criteria set out above.","In an example, the nucleotide sequence is SEQ ID NO: 29.In an example, the nucleotide sequence is SEQ ID NO: 30.In an example, the nucleotide sequence is SEQ ID NO: 31.In an example, the nucleotide sequence is SEQ ID NO: 32.In an example, the nucleotide sequence is SEQ ID NO: 33.In an example, the nucleotide sequence is SEQ ID NO: 34.In an example, the nucleotide sequence is SEQ ID NO: 35.In an example, the nucleotide sequence is SEQ ID NO: 36.In an example, the nucleotide sequence is SEQ ID NO: 37.The ligand can be any anti-PCSK9 ligand disclosed herein.","In a Twenty-Eight Aspect: The use of aspect 26 or 27, wherein the ligand, human, disease or condition is according to any one of aspects 1 to 19.In a Twenty-Ninth Aspect: A method of targeting a PCSK9 for treating and/or preventing a PCSK9-mediated disease or condition in a human, the method comprising administering an anti-PCSK9 ligand to a human comprising a nucleotide sequence selected from the group consisting SEQ ID NOs: 29-37, whereby a PCSK9 encoded by said nucleotide sequence is targeted.","The ligand can be any anti-PCSK9 ligand disclosed herein.","In a Thirtieth Aspect: The method of aspect 29, wherein the method comprises targeting a human PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q with said ligand to treat and/or prevent said disease or condition in said human.","In an example, said forms are the mature forms.","In an example, said forms are the pro-forms.","In a Thirty-first Aspect: A method of treating and/or preventing a disease or condition mediated by PCSK9 in a human, the method comprising targeting a human PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q by administering to the human a ligand that binds said PCSK9 thereby treating and/or preventing said disease or condition in the human.","In an example, said forms are the mature forms.","In an example, said forms are the pro-forms.","The ligand can be any anti-PCSK9 ligand disclosed herein.","In a Thirty-Second Aspect: The method of aspect 31, wherein the genome of the human comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37.In an example, the nucleotide sequence is selected from the group consisting of SEQ ID NOs: 29-35 and 37; or selected from the group consisting of SEQ ID NOs: 29-32 and 34-37; or selected from the group consisting of SEQ ID NOs: 29-32, 34, 35 and 37.These are naturally-occurring allele (haplotype) sequences that do not encode 46L and which meet the criteria set out above.","These groups comprise variants that are associated with elevated LDL-C.","In an example, the nucleotide sequence is SEQ ID NO: 34, that encodes a 425S, which is associated with elevated LDL-C (Pisciotta et al 2006).","In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31 and 37, that encode 670G which is a marker for severity of coronary atherosclerosis (Chen et al 2005).","In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35, 36 and 37; or selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35 and 37.These are allele (haplotype) sequences that have a naturally-occurring combination of differences from SEQ ID NO: 28 (form a) and which meet the criteria set out above.","In an example, the nucleotide sequence is SEQ ID NO: 29.In an example, the nucleotide sequence is SEQ ID NO: 30.In an example, the nucleotide sequence is SEQ ID NO: 31.In an example, the nucleotide sequence is SEQ ID NO: 32.In an example, the nucleotide sequence is SEQ ID NO: 33.In an example, the nucleotide sequence is SEQ ID NO: 34.In an example, the nucleotide sequence is SEQ ID NO: 35.In an example, the nucleotide sequence is SEQ ID NO: 36.In an example, the nucleotide sequence is SEQ ID NO: 37.In a Thirty-Third Aspect: The method of any one of aspects 29 to 32, wherein the human has been or is genotyped as positive for a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or the catalytic- or C-terminal domain-encoding sequence thereof.","In a Thirty-Fourth Aspect: The method of any one of aspects 29 to 33, wherein the human has been or is phenotyped as positive for a human PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q.","In an example, said forms are the mature forms.","In an example, said forms are the pro-forms.","In a Thirty-Fifth Aspect: The method of any one of aspects 29 to 34, wherein the method comprises genotyping the human as positive for a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or the catalytic- or C-terminal domain-encoding sequence thereof.","In a Thirty-Sixth Aspect: The method of any one of aspects 29 to 35, wherein the method comprises phenotyping the human as positive for a human PCSK9 sequence selected from the group consisting of forms f, c, r, p, m, e, h, aj and q.","In an example, said forms are the mature forms.","In an example, said forms are the pro-forms.","In a Thirty-seventh Aspect: The method of any one of aspects 29 to 36, wherein the human has been or is genotyped as heterozygous for a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or the catalytic- or C-terminal domain-encoding sequence thereof, optionally wherein the human has been or is genotyped as comprising the nucleotide sequence of SEQ ID NO: 28 or the catalytic- or C-terminal domain-encoding sequence thereof and a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or the catalytic- or C-terminal domain-encoding sequence thereof.","In a Thirty-Eighth Aspect: The method of any one of aspects 29 to 37, wherein the genome of the human has been or is genotyped as homozygous for a nucleotide sequence selected from the group consisting of of SEQ ID NOs: 29-37 or the catalytic- or C-terminal domain-encoding sequence thereof.","In a Thirty-Ninth Aspect: The method of any one of aspects 29 to 38, wherein the method comprises genotyping the human for a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or the catalytic- or C-terminal domain-encoding sequence thereof before administering the ligand to the human, wherein the ligand is determined to be capable of binding to a PCSK9 encoded by said selected sequence.","In a Fortieth Aspect: The method of any one of aspects 29 to 39, wherein the ligand, human, disease or condition is according to any one of aspects 1 to 19.In a Forty-First Aspect: A method according to any one of aspects 29 to 40 for treating and/or preventing a condition or disease as recited in aspect 14 or 15, the method comprising administering said ligand and a statin (eg, cerovastatin, atorvastatin, simvastatin, pitavastin, rosuvastatin, fluvastatin, lovastatin or pravastatin) to the human.","In a Forty-Second Aspect: The method of aspect 41, wherein the ligand and statin are administered separately.","In a Forty-Third Aspect: The method of aspect 41, wherein the ligand and statin are administered simultaneously.","In a Forty-Fourth Aspect: The method of any one of aspects 29 to 43, wherein the ligand is administered by subcutaneous injection.","In a Forty-Fifth Aspect: A method of PCSK9 genotyping a nucleic acid sample of a human, the method comprising identifying in the sample the presence of a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or the catalytic- or C-terminal domain-encoding sequence thereof.","In a Forty-Sixth Aspect: A method of PCSK9 typing a protein sample of a human, the method comprising identifying in the sample the presence of a human PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q.","In an example, said forms are the mature forms.","In an example, said forms are the pro-forms.","In a Forty-Seventh Aspect: The method of aspect 45 or 46, comprising obtaining a sample of serum, blood, faeces, hair, tissue, cells, urine or saliva from a human, whereby the nucleic acid or protein sample is obtained and used in the step of identifying said sequence.","In a Forty-Eighth Aspect: The method of any one of aspects 45 to 47, comprising using a ligand according to any one of aspects 1 to 19 to carry out said identifying step.","In a Forty-Ninth Aspect: A method of treating and/or preventing in a human patient a cardiovascular disease or condition, or a disease or condition that is associated with elevated LDL cholesterol (eg, hypercholesterolaemia), wherein the patient is receiving or has previously received statin treatment for said disease or condition, the method comprising typing the patient using a method of any one of aspects 45 to 48 and administering a ligand according to one of aspects 1 to 19 whereby the human is treated or said disease or condition is prevented; optionally also reducing or stopping statin treatment.","In an example, said reducing or stopping comprises reducing the dose and/or dosing frequency of statin.","In a Fiftieth Aspect: A diagnostic, therapeutic or prophylactic kit comprising a ligand that is capable of binding to or has been or is determined as capable of binding to an amino acid sequence selected from SEQ ID NOs: 4-27 and instructions for carrying out the method of any one of aspects 46 to 49 and/or a label or instructions indicating or covering administration of the ligand to a human as defined in any one of aspects 1 to 19.In a Fifty-First Aspect: A diagnostic, therapeutic or prophylactic kit comprising a nucleic acid probe comprising a nucleotide sequence that specifically hybridises to a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or an antisense sequence or RNA transcript thereof and instructions for carrying out the method of aspect 45, 47 or 48.In examples of the present invention, the ligand specifically binds to human PCSK9, eg, one or more of the rare PCSK9 variants disclosed herein (eg, one, two, three, more or all mature forms f, c, r, p, m, e, h, aj and q) and optionally also the a and/or a′ form.","For example, the ligand specifically binds to mature form f and/or c as well as form a.","Determination of such binding can be performed by any antibody binding test as known in the art, eg, by surface plasmon resonance.","Binding to each such form is, for example, respectively with a Kd of at least 1 mM, 100 nM, 1 nM, 100 pM, 10 pM or 1 pM.","In an example, the ligand binds form a and a PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q, wherein the ligand binding to said selected form is with a Kd (determined by SPR) that is at least 60, 70, 80, 90 or 95% of the Kd for binding to form a.","In an embodiment, both forms are mature forms.","In an embodiment, both forms are pro-forms.","In an example, the ligand binds form a and form f, wherein the ligand binding to form f is with a Kd (determined by SPR) that is at least 60, 70, 80, 90 or 95% of the Kd for binding to form a.","In an embodiment, both forms are mature forms.","In an embodiment, both forms are pro-forms.","In an example, the ligand binds form a and form c, wherein the ligand binding to form c is with a Kd (determined by SPR) that is at least 60, 70, 80, 90 or 95% of the Kd for binding to form a.","In an embodiment, both forms are mature forms.","In an embodiment, both forms are pro-forms.","In an example, the ligand binds form a and form r, wherein the ligand binding to form r is with a Kd (determined by SPR) that is at least 60, 70, 80, 90 or 95% of the Kd for binding to form a.","In an embodiment, both forms are mature forms.","In an embodiment, both forms are pro-forms.","In an example, the ligand binds form a and form p, wherein the ligand binding to form p is with a Kd (determined by SPR) that is at least 60, 70, 80, 90 or 95% of the Kd for binding to form a.","In an embodiment, both forms are mature forms.","In an embodiment, both forms are pro-forms.","In an example, the ligand binds form a and form m, wherein the ligand binding to form m is with a Kd (determined by SPR) that is at least 60, 70, 80, 90 or 95% of the Kd for binding to form a.","In an embodiment, both forms are mature forms.","In an embodiment, both forms are pro-forms.","In an example, the ligand binds form a and form e, wherein the ligand binding to form e is with a Kd (determined by SPR) that is at least 60, 70, 80, 90 or 95% of the Kd for binding to form a.","In an embodiment, both forms are mature forms.","In an embodiment, both forms are pro-forms.","In an example, the ligand binds form a and form h, wherein the ligand binding to form h is with a Kd (determined by SPR) that is at least 60, 70, 80, 90 or 95% of the Kd for binding to form a.","In an embodiment, both forms are mature forms.","In an embodiment, both forms are pro-forms.","In an example, the ligand binds form a and form aj, wherein the ligand binding to form aj is with a Kd (determined by SPR) that is at least 60, 70, 80, 90 or 95% of the Kd for binding to form a.","In an embodiment, both forms are mature forms.","In an embodiment, both forms are pro-forms.","In an example, the ligand binds form a and form q, wherein the ligand binding to form q is with a Kd (determined by SPR) that is at least 60, 70, 80, 90 or 95% of the Kd for binding to form a.","In an embodiment, both forms are mature forms.","In an embodiment, both forms are pro-forms.","In examples of the present invention, the ligand neutralises human PCSK9, eg, one or more of the rare PCSK9 variants disclosed herein (eg, one, two, three, more or all mature forms f, c, r, p, m, e, h, aj and q) and optionally also the a and/or a′ form.","For example, the ligand neutralises mature form f and/or c as well as form a.","Determination of neutralisation can be performed, for example, by any neutralisation assay method disclosed in US20120093818A1 (Amgen, Inc) or US20110065902A1 (Regeneron Pharmaceuticals, Inc).","Ligands of the invention that bind or target PCSK9 are useful, for example, for therapeutic and prophylactic applications disclosed in US20120093818A1 and US20110065902A1, these specific disclosures being incorporated herein by reference for use in the present invention and for possible inclusion in claims herein.","In embodiments where the ligand is used for therapeutic applications, an antigen binding protein can inhibit, interfere with or modulate one or more biological activities of a PCSK9 (eg, one or more of the rare variants disclosed herein and optionally also the a and/or a′ form).","In one embodiment, ligand binds specifically to human PCSK9 (eg, one or more of the rare variants disclosed herein and optionally also the a and/or a′ form) and/or substantially inhibits binding of human PCSK9 (eg, said one or more of the rare variants disclosed herein and optionally also the a and/or a′ form) to LDLR by at least 20%, eg, 20%-40%, 40-60%, 60-80%, 80-85%, or more (for example, by measuring binding in an in vitro competitive binding assay).","In an example, the ligand is an antibody.","In an embodiment, the ligand has a Kd of less (binding more tightly) than 10−7, 10−8, 10−9, 10−10, 10−11, 10−12, 10−13 M for binding to one, two or more of the rare variants disclosed herein and optionally also the a and/or a′ form.","In an example, Kd is determined using SPR.","In an embodiment, the ligand has an IC50 for blocking the binding of LDLR to one or more of the rare PCSK9 variants disclosed herein (and optionally also the a and/or a′ form) of less than 1 microM, 1000 nM to 100 nM, 100 nM to 10 nM, 10 nM to 1 nM, 1000 pM to 500 pM, 500 pM to 200 pM, less than 200 pM, 200 pM to 150 pM, 200 pM to 100 pM, 100 pM to 10 pM, 10 pM to 1 pM.","In an embodiment, the ligand has an IC50 for blocking the binding of LDLR to the a and/or a′ form of PCSK9 that is no more than 1000, 100, 90, 80, 70, 60, 50, 40, 30, 20 or 10-fold more (ie, more inhibitory) than the IC50 for blocking the binding of LDLR to one or more of the rare PCSK9 variants disclosed herein (eg, one or more PCSK9 proteins comprising a sequence selected from SEQ ID NOs: 4 to 27).","Additionally or alternatively, for example, the ligand has an IC50 for blocking the binding of LDLR to (i) the a and/or a′ form of less than 1 microM, 1000 nM to 100 nM, 100 nM to 10 nM, 10 nM to 1 nM, 1000 pM to 500 pM, 500 pM to 200 pM, less than 200 pM, 200 pM to 150 pM, 200 pM to 100 pM, 100 pM to 10 pM, 10 pM to 1 pM, eg, in the range of 1 mM to 1 pM (eg, 1 mM to 100 pM; 10 nM to 100 pM; 1 nM to 10 pM; or 100 pM to 1 pM) and (ii) one or more PCSK9 proteins comprising a sequence selected from SEQ ID NOs: 4 to 27 of less than 1 microM, 1000 nM to 100 nM, 100 nM to 10 nM, 10 nM to 1 nM, 1000 pM to 500 pM, 500 pM to 200 pM, less than 200 pM, 200 pM to 150 pM, 200 pM to 100 pM, 100 pM to 10 pM, 10 pM to 1 pM, eg, in the range of 1 mM to 1 pM (eg, 1 mM to 100 pM; 10 nM to 100 pM; 1 nM to 10 pM; or 100 pM to 1 pM).","In an embodiment, the ligand binds to the a and/or a′ form of PCSK9 with a binding affinity (Kd) that is greater than up to 10%, greater than up to 20%, greater than up to 40%, greater than up to 50%, greater than up to 55%, greater than up to 60%, greater than up to 65%, greater than up to 70%, greater than up to 75%, greater than up to 80%, greater than up to 85%, greater than up to 90%, greater than up to 95% or greater than up to 100% (ie, is double) relative to binding to a PCSK9 comprising a sequence selected from SEQ ID NOs: 4 to 27.Such binding measurements can be made using a variety of binding assays known in the art, eg, using surface plasmon resonance (SPR), such as by Biacore™ or using the ProteOn XPR36™ (Bio-Rad®), or using KinExA® (Sapidyne Instruments, Inc).","In one embodiment, the surface plasmon resonance (SPR) is carried out at 25° C. In another embodiment, the SPR is carried out at 37° C. In one embodiment, the SPR is carried out at physiological pH, such as about pH7 or at pH7.6 (eg, using Hepes buffered saline at pH7.6 (also referred to as HBS-EP)).","In one embodiment, the SPR is carried out at a physiological salt level, eg, 150 mM NaCl.","In one embodiment, the SPR is carried out at a detergent level of no greater than 0.05% by volume, eg, in the presence of P20 (polysorbate 20; eg, Tween-20™) at 0.05% and EDTA at 3 mM.","In one example, the SPR is carried out at 25° C. or 37° C. in a buffer at pH7.6, 150 mM NaCl, 0.05% detergent (eg, P20) and 3 mM EDTA.","The buffer can contain 10 mM Hepes.","In one example, the SPR is carried out at 25° C. or 37° C. in HBS-EP.","HBS-EP is available from Teknova Inc (California; catalogue number H8022).","In an example, the affinity of the ligand which is an antibody is determined using SPR by 1.Coupling anti-mouse (or other relevant vertebrate) IgG (eg, Biacore BR-1008-38) to a biosensor chip (eg, GLM chip) such as by primary amine coupling; 2.Exposing the anti-mouse IgG (vertebrate antibody) to a test IgG antibody to capture test antibody on the chip; 3.Passing the test antigen over the chip's capture surface at 1024 nM, 256 nM, 64 nM, 16 nM, 4 nM with a 0 nM (i.e.","buffer alone); and 4.And determining the affinity of binding of test antibody to test antigen using surface plasmon resonance, eg, under an SPR condition discussed above (eg, at 25° C. in physiological buffer).","SPR can be carried out using any standard SPR apparatus, such as by Biacore™ or using the ProteOn XPR36™ (Bio-Rad®).","Regeneration of the capture surface can be carried out with 10 mM glycine at pH1.7.This removes the captured antibody and allows the surface to be used for another interaction.","The binding data can be fitted to 1:1 model inherent using standard techniques, eg, using a model inherent to the ProteOn XPR36™ analysis software.","In an embodiment, assaying or testing of a ligand of the invention is carried out at or substantially at pH7 (eg, for in vitro tests and assays) and at or substantially at rtp.","One example of an IgG2 heavy chain constant domain of an anti-PCSK9 antibody of the present invention has the amino acid sequence as shown in SEQ ID NO: 154, FIG.","3KK of US20120093818A1, which sequence is incorporated herein by reference.","One example of an IgG4 heavy chain constant domain of an anti-PCSK9 antibody of the present invention has the amino acid sequence as shown in SEQ ID NO: 155, FIG.","3KK of US20120093818A1, which sequence is incorporated herein by reference.","One example of a kappa light chain constant domain of an anti-PCSK9 antibody has the amino acid sequence as shown in SEQ ID NO: 157, FIG.","3KK which sequence is incorporated herein by reference.","One example of a lambda light chain constant domain of an anti-PCSK9 antibody has the amino acid sequence as shown in SEQ ID NO: 156, FIG.","3KK of US20120093818A1, which sequence is incorporated herein by reference.","In examples of the present invention, the ligand binds mature PCSK9, eg, a mature form of one or more of the rare variants disclosed herein and optionally also the a and/or a′ form.","In examples of the present invention, the ligand binds the catalytic domain of PCSK9, eg, of a mature form of one or more of the rare variants disclosed herein and optionally also the a and/or a′ form.","In examples of the present invention, the ligand binds the prodomain of PCSK9, eg, of a mature form of one or more of the rare variants disclosed herein and optionally also the a and/or a′ form.","In some embodiments, the ligand binds to the V domain of PCSK9, eg, of a mature form of one or more of the rare variants disclosed herein and optionally also the a and/or a′ form.","In some embodiments, the ligand binds to the V domain of PCSK9 (eg, of a mature form of one or more of the rare variants disclosed herein and optionally also the a and/or a′ form) and prevents (or reduces, eg, by at least 10%) PCSK9 from binding to LDLR.","In some embodiments, the ligand binds to the V domain of PCSK9 (eg, of a mature form of one or more of the rare variants disclosed herein and optionally also the a and/or a′ form), and while it does not prevent (or reduce) the binding of PCSK9 to LDLR, the ligand prevents or reduces (eg, by at least 10%) the adverse activities mediated through PCSK9 on LDLR.","In examples of the present invention, the ligand is or comprises a fully human antibody.","In an example, the ligand comprises human variable regions or humanised variable regions.","In an example, the ligand of the invention specifically binds to an epitope of a human PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q, wherein the epitope comprises at least one amino acid that is not found in form a.","For example, the amino acid is selected from the group consisting of 46L, 53V, 425S, 443T, 474V, 619P and 670G (numbering as used in SEQ ID NO: 1).","For example, the amino acid is selected from the group consisting of 425S, 443T, 474V, 619P and 670G (numbering as used in SEQ ID NO: 1).","For example, the amino acid is selected from the group consisting of 425S and 443T (numbering as used in SEQ ID NO: 1).","For example, the amino acid is selected from the group consisting of 474V, 619P and 670G (numbering as used in SEQ ID NO: 1).","In an example, the PCSK9 form is the mature form.","In an example, the PCSK9 form is the pro-form.","In an example, the ligand also specifically binds to form a and/or a′.","In an embodiment, the ligand specifically binds to an epitope of form f PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to an epitope of form c PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to an epitope of form r PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to an epitope of form p PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to an epitope of form m PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to an epitope of form e PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to an epitope of form h PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to an epitope of form aj PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to an epitope of form q PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, ligand binds specifically to the pro-domain of a human PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q.","In an example, the ligand also specifically binds to the pro-domain of form a and/or a′.","In an embodiment, the ligand specifically binds to the pro-domain of form f PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the pro-domain of form c PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the pro-domain of form r PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the pro-domain of form p PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the pro-domain of form m PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the pro-domain of form e PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the pro-domain of form h PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the pro-domain of form aj PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the pro-domain of form q PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, ligand binds specifically to the catalytic domain of a human PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q.","In an example, the ligand also specifically binds to the catalytic domain of form a and/or a′.","In an embodiment, the ligand specifically binds to the catalytic domain of form f PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the catalytic domain of form c PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the catalytic domain of form r PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the catalytic domain of form p PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the catalytic domain of form m PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the catalytic domain of form e PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the catalytic domain of form h PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the catalytic domain of form aj PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the catalytic domain of form q PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, ligand binds specifically to the C-terminal domain of a human PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q.","In an example, the ligand also specifically binds to the C-terminal domain of form a and/or a′.","In an embodiment, the ligand specifically binds to the C-terminal domain of form f PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the C-terminal domain of form c PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the C-terminal domain of form r PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the C-terminal domain of form p PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the C-terminal domain of form m PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the C-terminal domain of form e PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the C-terminal domain of form h PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the C-terminal domain of form aj PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the C-terminal domain of form q PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, ligand binds specifically to the substrate-binding groove of a human PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q (see Cunningham et al., Nat Struct Mol Biol.","2007 May; 14(5):413-9.Epub 2007 Apr.","15, “Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia”, incorporated herein in its entirety by reference).","In an example, the ligand also specifically binds to the substrate-binding groove of form a and/or a′.","In an embodiment, the ligand specifically binds to the Substrate-binding groove of form f PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the Substrate-binding groove of form c PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the Substrate-binding groove of form r PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the Substrate-binding groove of form p PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the Substrate-binding groove of form m PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the Substrate-binding groove of form e PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the Substrate-binding groove of form h PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the Substrate-binding groove of form aj PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","In an embodiment, the ligand specifically binds to the Substrate-binding groove of form q PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.","Reference is made to US20120093818A1 (Amgen, Inc), the entire disclosure of which is incorporated herein.","This patent application discloses relevant ligands for use in the present invention, as well as examples and methods of producing and testing ligands that can be used with reference to the present invention.","In an example, the ligand is or comprises an antibody disclosed in Table 2 of US20120093818A1 (Amgen, Inc) or is a PCSK9-binding derivative thereof.","In an embodiment, the PCSK9-binding ligand of the invention is selected from the antigen binding proteins disclosed in US20120093818A1 (Amgen, Inc), eg, in paragraphs [0009] to [0014] and [0058] to [0063] of US20120093818A1; all of these disclosures (including the sequences of such proteins) are incorporated herein by reference as though explicitly recited herein and for possible inclusion in one or more claims or for use in the present invention.","In this paragraph SEQ ID NOs are those as appearing in US20120093818A1 (Amgen, Inc) and these sequences are incorporated herein by reference as though explicitly recited herein and for possible inclusion in one or more claims or for use in the present invention.","In some aspects, the ligand of the invention comprises an isolated antigen binding protein that binds PCSK9 comprising: A) one or more heavy chain complementary determining regions (CDRHs) selected from the group consisting of: (i) a CDRH1 from a CDRH1 in a sequence selected from the group consisting of SEQ ID NO: 74, 85, 71, 72, 67, 87, 58, 52, 51, 53, 48, 54, 55, 56, 49, 57, 50, 91, 64, 62, 89, 65, 79, 80, 76, 77, 78, 83, 69, 81, and 60; (ii) a CDRH2 from a CDRH2 in a sequence selected from the group consisting of SEQ ID NO: 74, 85, 71, 72, 67, 87, 58, 52, 51, 53, 48, 54, 55, 56, 49, 57, 50, 91, 64, 62, 89, 65, 79, 80, 76, 77, 78, 83, 69, 81, and 60; (iii) a CDRH3 from a CDRH3 in a sequence selected from the group consisting of SEQ ID NO: 74, 85, 71, 72, 67, 87, 58, 52, 51, 53, 48, 54, 55, 56, 49, 57, 50, 91, 64, 62, 89, 65, 79, 80, 76, 77, 78, 83, 69, 81, and 60; and (iv) a CDRH of (i), (ii), and (iii) that contains one or more amino acid substitutions, deletions or insertions of no more than 4 amino acids; B) one or more light chain complementary determining regions (CDRLs) selected from the group consisting of: (i) a CDRL1 from a CDRL1 in a sequence selected from the group consisting of SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, and 46; (ii) a CDRL2 from a CDRL2 in a sequence selected from the group consisting of SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, and 46; (iii) a CDRL3 from a CDRL3 in a sequence selected from the group consisting of SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, and 46; and (iv) a CDRL of (i), (ii) and (iii) that contains one or more amino acid substitutions, deletions or insertions of no more than 4 amino acids; or C) one or more heavy chain CDRHs of A) and one or more light chain CDRLs of B).","In some embodiments, the isolated antigen binding protein comprises at least one CDRH of A) and at least one CDRL of B).","In some embodiments, the isolated antigen binding protein comprises at least two CDRH of A) and at least two CDRL of B).","In some embodiments, the isolated antigen binding protein comprises said CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3.In some embodiments, the CDRH of A) is selected from at least one of the group consisting of: (i) a CDRH1 amino acid sequence selected from the CDRH1 in a sequence selected from the group consisting of SEQ ID NO: 67, 79, 89, and 49; (ii) a CDRH2 amino acid sequence selected from the CDRH2 in a sequence selected from the group consisting of SEQ ID NO: 67, 79, 89, and 49; (iii) a CDRH3 amino acid sequence selected from the CDRH3 in a sequence selected from the group consisting of SEQ ID NO: 67, 79, 89, and 49; and (iv) a CDRH of (i), (ii) and (iii) that contains one or more amino acid substitutions, deletions or insertions of no more than 2 amino acids.","In addition, the CDRL of B) is selected from at least one of the group consisting of: (i) a CDRL1 amino acid sequence selected from the CDRL1 in a sequence selected from the group consisting of SEQ ID NO: 12, 35, 32, and 23; (ii) a CDRL2 amino acid sequence selected from the CDRL2 in a sequence selected from the group consisting of SEQ ID NO: 12, 35, 32, and 23; (iii) a CDRL3 amino acid sequence selected from the CDRL3 in a sequence selected from the group consisting of SEQ ID NO: 12, 35, 32, and 23; and (iv) a CDRL of (i), (ii) and (iii) that contains one or more amino acid substitutions, deletions or insertions of no more than 2 amino acids; or C) one or more heavy chain CDRHs of A) and one or more light chain CDRLs of B.","In some embodiments, the CDRH of A) is selected from at least one of the group consisting of: (i) a CDRH1 amino acid sequence of the CDRH1 amino acid sequence in SEQ ID NO: 67; (ii) a CDRH2 amino acid sequence of the CDRH2 amino acid sequence in SEQ ID NO: 67; (iii) a CDRH3 amino acid sequence of the CDRH3 amino acid sequence in SEQ ID NO: 67; and (iv) a CDRH of (i), (ii) and (iii) that contains one or more amino acid substitutions, deletions or insertions of no more than 2 amino acids; said CDRL of B) is selected from at least one of the group consisting of: (i) a CDRL1 amino acid sequence of the CDRL1 amino acid sequence in SEQ ID NO: 12; (ii) a CDRL2 amino acid sequence of the CDRL2 amino acid sequence in SEQ ID NO: 12; (iii) a CDRL3 amino acid sequence of the CDRL3 amino acid sequence in SEQ ID NO: 12; and (iv) a CDRL of (i), (ii) and (iii) that contains one or more amino acid substitutions, deletions or insertions of no more than 2 amino acids; or C) one or more heavy chain CDRHs of A) and one or more light chain CDRLs of B).","In some embodiments, the antigen binding protein comprises A) a CDRH1 of the CDRH1 sequence in SEQ ID NO: 67, a CDRH2 of the CDRH2 sequence in SEQ ID NO: 67, and a CDRH3 of the CDRH3 sequence in SEQ ID NO: 67, and B) a CDRL1 of the CDRL1 sequence in SEQ ID NO: 12, a CDRL2 of the CDRL2 sequence in SEQ ID NO: 12, and a CDRL3 of the CDRL3 sequence in SEQ ID NO: 12.In some embodiments, the antigen binding protein comprises a heavy chain variable region (VH) having at least 80% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NO: 74, 85, 71, 72, 67, 87, 58, 52, 51, 53, 48, 54, 55, 56, 49, 57, 50, 91, 64, 62, 89, 65, 79, 80, 76, 77, 78, 83, 69, 81, and 60, and/or a light chain variable region (VL) having at least 80% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, and 46.In some embodiments, the VH has at least 90% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NO: 74, 85, 71, 72, 67, 87, 58, 52, 51, 53, 48, 54, 55, 56, 49, 57, 50, 91, 64, 62, 89, 65, 79, 80, 76, 77, 78, 83, 69, 81, and 60, and/or the VL has at least 90% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, and 46.In some embodiments, the VH is selected from the group consisting of SEQ ID NO: 74, 85, 71, 72, 67, 87, 58, 52, 51, 53, 48, 54, 55, 56, 49, 57, 50, 91, 64, 62, 89, 65, 79, 80, 76, 77, 78, 83, 69, 81, and 60, and/or the VL is selected from the group consisting of SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, and 46.In an example of any aspect of the invention, the PCSK9-targeting or binding ligand comprises or consists of AMG145 or 31H4, 16F12, 11F1, 8A3 or 21B12 disclosed in US20120093818A1 (Amgen, Inc) or an antibody comprising the variable domains of AMG145, 31H4, 16F12, 11F1, 8A3 or 21B12, the disclosures of which (including sequences) are incorporated herein by reference as though explicitly recited herein and for possible inclusion in one or more claims or for use in the present invention.","Preferably, the PCSK9-targeting or binding ligand comprises or consists of AMG145.In an example, the AMG145 or other ligand of the invention is glycosylated, eg, has human glycosylation (eg, produced by a CHO, Cos or Hek293 cell).","In an example, the ligand of the invention is produced in CHO.","Reference is made to US20110065902A1 (Regeneron Pharmaceuticals, Inc), the entire disclosure of which is incorporated herein.","This patent application discloses relevant ligands for use in the present invention, as well as examples and methods of producing and testing ligands and determining medical efficacy that can be used with reference to the present invention.","Reference is made to the following PCT applications, the entire disclosures of which are incorporated herein.","These disclose relevant ligands for use in the present invention, as well as examples and methods of producing and testing ligands and determining medical efficacy that can be used with reference to the present invention.","WO2008057457 WO2008057458 WO2008057459 WO2008063382 WO2008133647 WO2009100297 WO2009100318 WO2011037791 WO2011053759 WO2011053783 WO2008125623 WO2011072263 WO2009055783 WO2010029513 WO2011111007 WO2010077854 Antibody ligands to PCSK9 are described in, for example, WO 2008/057457, WO 2008/057458, WO 2008/057459, WO 2008/063382, WO 2008/125623, and US 2008/0008697; each of which is incorporated by reference herein in its entirety.","In an example, the ligand is or comprises an antibody disclosed in the Examples of US20110065902A1 (eg, 316P or 300N) or is a PCSK9-binding derivative thereof.","All of these disclosures (including the sequences of such proteins and corresponding nucleotide sequences) are incorporated herein by reference as though explicitly recited herein and for possible inclusion in one or more claims or for use in the present invention.","In an embodiment, the ligand is or comprises the variable domains of antibody 316P or 300N disclosed in US20110065902A1 or is (or comprises) such antibody or a PCSK9-binding derivative thereof.","In an embodiment, the ligand is or comprises the variable domains of antibody alirocumab or SAR236553/REGN727 (Sanofi Aventis/Regeneron) or is (or comprises) such antibody or a PCSK9-binding derivative thereof.","In an example, the alirocumab is glycosylated, eg, has human glycosylation (eg, produced by a CHO, Cos or Hek293 cell).","Preferably, the ligand is alirocumab or SAR236553/REGN727.In an embodiment, the ligand is or comprises the variable domains of antibody evolocumab or or is (or comprises) such antibody or a PCSK9-binding derivative thereof.","In an example, the antibody is glycosylated, eg, has human glycosylation (eg, produced by a CHO, Cos or Hek293 cell).","Preferably, the ligand is evolocumab.","In an embodiment, the ligand is selected from evolocumab, 1D05-IgG2 (Merck & Co.), ALN-PCS02 (Alnylam), RN316 (Pfizer-Rinat) and alirocumab.","In an embodiment, the ligand is selected from the following (sequences and definitions as per US2011/0065902, incorporated herein by reference):— 1.An antibody or antigen-binding fragment thereof which specifically binds hPCSK9, wherein the antibody or antigen-binding fragment comprises the heavy and light chain CDRs of a HCVR/LCVR amino acid sequence pair having SEQ ID NOs: 218/226.2.The antibody or antigen-binding fragment of concept 1 comprising heavy and light chain CDR amino acid sequences having SEQ ID NOs: 220, 222, 224, 228, 230 and 232.3.The antibody or antigen-binding fragment of concept 2 comprising an HCVR having the amino acid sequence of SEQ ID NO: 218 and an LCVR having the amino acid sequence of SEQ ID NO: 226.4.An antibody or antigen-binding fragment thereof which binds to the same epitope on hPCSK9 as an antibody comprising heavy and light chain CDR amino acid sequences having SEQ ID NOs: 220, 222, 224, 228, 230 and 232.5.An antibody or antigen-binding fragment thereof which competes for binding to hPCSK9 with an antibody comprising heavy and light chain CDR amino acid sequences having SEQ ID NOs: 220, 222, 224, 228, 230 and 232.In an embodiment, the ligand is selected from the following (sequences and definitions as per US2012/0093818, incorporated herein by reference):— 1.An isolated neutralizing antigen binding protein that binds to a PCSK9 protein comprising the amino acid sequence of SEQ ID NO: 1, wherein the neutralizing antigen binding protein decreases the LDLR lowering effect of PCSK9 on LDLR, wherein the antigen binding protein comprises a light chain comprising an amino acid sequence of SEQ ID NO: 46, and wherein the antigen binding protein comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 60.2.The isolated neutralizing antigen binding protein of concept 2, wherein the antigen binding protein is a LDLR non-competitive neutralizing antigen binding protein.","3.The isolated neutralizing antigen binding protein of concept 2, wherein the antigen binding protein is a LDLR competitive neutralizing antigen binding protein.","4.An antigen binding protein that selectively binds to PCSK9, wherein said antigen binding protein binds to PCSK9 with a Kd that is less than 100 pM.","5.An antigen binding protein that binds to a PCSK9 protein of SEQ ID NO: 303 in a first manner, wherein the antigen binding protein binds to a variant of PCSK9 in a second manner, wherein said PCSK9 variant has at least one point mutation at a position selected from the group consisting of: 207, 208, 185, 181, 439, 513, 538, 539, 132, 351, 390, 413, 582, 162, 164, 167, 123, 129, 311, 313, 337, 519, 521, and 554 of SEQ ID NO: 303, wherein the first manner comprises a first EC50, a first Bmax, or a first EC50 and a first Bmax, wherein the second manner comprises a second EC50, a second Bmax, or a second EC50 and a second Bmax, and wherein a value for the first manner is different from a value for the second manner, and wherein the antigen binding protein comprises a light chain comprising an amino acid sequence of SEQ ID NO: 46, and wherein the antigen binding protein comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 60.6.The antigen binding protein of concept 6, wherein the first manner comprises a first Bmax, wherein the second manner comprises a second Bmax that is different from the first Bmax, and wherein said PCSK9 variant has at least one point mutation selected from the group consisting of: D162R, R164E, E167R, S123R, E129R, A311R, D313R, D337R, R519E, H521R, and Q554R.","7.The antigen binding protein of concept 6, wherein the antigen binding protein binds to PCSK9 at a location that overlaps with a location that LDLR binds to PCSK9.8.A method of making an antigen binding protein that binds to a PCSK9 protein comprising the amino acid sequence of SEQ ID NO: 1, wherein the antigen binding protein decreases the LDLR lowering effect of PCSK9 on LDLR, said method comprising: providing a host cell comprising a nucleic acid sequence that encodes the antigen binding protein; and maintaining the host cell under conditions in which the antigen binding protein is expressed, wherein the antigen binding protein comprises a light chain comprising an amino acid sequence of SEQ ID NO: 46, and wherein the antigen binding protein comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 60.9.A method for treating or preventing a condition associated with elevated serum cholesterol levels in a subject, said method comprising administering to a subject in need thereof an effective amount of an isolated neutralizing antigen binding protein simultaneously or sequentially with an agent that elevates the availability of LDLR protein, wherein the isolated antigen binding protein binds to a PCSK9 protein comprising the amino acid sequence of SEQ ID NO: 1, wherein the neutralizing antigen binding protein decreases the LDLR lowering effect of PCSK9 on LDLR, wherein the antigen binding protein comprises a light chain comprising an amino acid sequence of SEQ ID NO: 46, and wherein the antigen binding protein comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 60.10.The method of concept 10, wherein the agent that elevates the availability of LDLR protein comprises a statin.","11.An antigen binding protein that binds to PCSK9, wherein when the antigen binding protein is bound to PCSK9, the antibody is positioned 8 angstroms or less from at least one of the following residues of PCSK9: S153, S188, I189, Q190, S191, D192, R194, E197, G198, R199, V200, D224, R237, D238, K243, S373, D374, S376, T377, F379, I154, T187, H193, E195, I196, M201, V202, C223, T228, S235, G236, A239, G244, M247, 1369, S372, C375, or C378, wherein the antigen binding protein comprises a light chain comprising an amino acid sequence of SEQ ID NO: 46, and wherein the antigen binding protein comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 60.The ligand can be used for the treatment, therapy, prophylaxis and/or diagnosis of one or more diseases or conditions or susceptibility thereto, wherein such diseases or conditions comprise those disclosed in US20120093818A1 (Amgen, Inc) and US20110065902A1 (Regeneron Pharmaceuticals, Inc), eg, a disease or condition disclosed in paragraphs [0375] to [0383] of US20120093818A1, which disclosure is incorporated herein by reference in its entirety for inclusion in one more claims herein.","The ligand can be administered to a human characterised as described in US20120093818A1 (Amgen, Inc) or US20110065902A1.The ligand can be administered in a form or combination disclosed in US20120093818A1 (Amgen, Inc) or US20110065902A1, which disclosure is incorporated herein by reference.","For example, the ligand with a drug, excipient, diluent or carrier as described in US20120093818A1 (Amgen, Inc) or US20110065902A1 (eg, as disclose in paragraphs [0384] to [0412] of US20120093818A1), which disclosure is incorporated herein by reference, and the present invention also relates to the corresponding pharmaceutical compositions comprising the combination of a ligand of the invention and such a further agent.","The ligand can be used in a method of diagnosis as set out in US20120093818A1 (Amgen, Inc) or US20110065902A1, eg, in paragraphs [0413] to [0415] of US20120093818A1 which disclosure is incorporated herein by reference.","Diagnostic Applications In some embodiments, the ligand of the invention is a diagnostic tool.","The ligand can be used to assay the amount of PCSK9 present in a sample and/or subject.","As will be appreciated by one of skill in the art, such ligands need not be neutralizing ligands.","In some embodiments, the diagnostic ligand is not a neutralizing ligand.","In some embodiments, the diagnostic ligand binds to a different epitope than a neutralizing ligand binds to.","In some embodiments, the two ligands do not compete with one another.","In some embodiments, the ligands of the invention are used or provided in an assay kit and/or method for the detection of PCSK9 in mammalian tissues or cells in order to screen/diagnose for a disease or disorder associated with changes in levels of PCSK9.The kit comprises a ligand that binds PCSK9 and means for indicating the binding of the ligand with PCSK9, if present, and optionally PCSK9 protein levels.","Various means for indicating the presence of a ligand can be used.","For example, fluorophores, other molecular probes, or enzymes can be linked to the ligand and the presence of the ligand can be observed in a variety of ways.","The method for screening for such disorders can involve the use of the kit, or simply the use of one of the disclosed ligands and the determination of whether the ligand binds to PCSK9 in a sample.","As will be appreciated by one of skill in the art, high or elevated levels of PCSK9 will result in larger amounts of the ligand binding to PCSK9 in the sample.","Thus, degree of ligand binding can be used to determine how much PCSK9 is in a sample.","Subjects or samples with an amount of PCSK9 that is greater than a predetermined amount (e.g., an amount or range that a person without a PCSK9 related disorder would have) can be characterized as having a PCSK9 mediated disorder.","In some embodiments, the invention provides a method wherein the ligand is administered to a subject taking a statin, in order to determine if the statin has increased the amount of PCSK9 in the subject.","In some embodiments, the ligand is a non-neutralizing ligand and is used to determine the amount of PCSK9 in a subject receiving an ABP and/or statin treatment.","In some embodiments, the ligand of the invention can specifically bind human PCSK9 (eg, one, two or more rare variant forms disclosed herein) and is characterized by at least one of: (i) capable of reducing serum total cholesterol at least about 25-35% and sustaining the reduction over at least a 24 day period relative to a predose level; (ii) capable of reducing serum LDL cholesterol at least about 65-80% and sustaining the reduction over at least a 24 day period relative to a predose level; (iii) capable of reducing serum LDL cholesterol at least about 40-70% and sustaining the reduction over at least a 60 or 90 day period relative to a predose level; (iv) capable of reducing serum triglyceride at least about 25-40% relative to predose level; (v) does not reduce serum HDL cholesterol or reduces serum HDL cholesterol no more than 5% relative to predose level.","In some embodiments, an isolated nucleic acid molecule is provided and it encodes the ligand.","In some embodiments an expression vector is provided and comprises the nucleic acid molecule.","In some embodiments, a pharmaceutical composition is provided and it can comprise the ligand and a pharmaceutically acceptable carrier.","In some embodiments, a method is provided for treating a disease or condition which is ameliorated, improved, inhibited or prevented with a PCSK9 antagonist ligand of the invention.","The method can comprise administering a therapeutic amount of the pharmaceutical composition or ligand to a subject in need thereof.","In some embodiments, the subject is a human subject suffering from hypercholesterolemia, hyperlipidemia, indicated for LDL apheresis, identified as heterozygous for Familial Hypercholesterolemia, statin intolerant.","statin uncontrolled, at risk for developing hypercholesterolemia, dyslipidemia, cholestatic liver disease, nephrotic syndrome, hypothyroidism, obesity, atherosclerosis and cardiovascular diseases.","In some embodiments, a method of providing a treatment or therapy is provided to a subject.","In some embodiments, the method comprises reducing serum cholesterol at least about 40-70% over at least 60 to 90 days.","In some embodiments, a method of receiving treatment or therapy is provided, the method can comprise receiving a ligand thereof at a frequency of once every 60 to 90 days.","In one aspect, the invention provides a ligand of the invention which is or comprises an human antibody or antigen-binding fragment of a human antibody that specifically binds and inhibits human proprotein convertase subtilisin/kexin type 9 (hPCSK9, eg, one, two or more rare variant forms disclosed herein and optionally form a and/or form a′), characterized by the ability to reduce serum LDL cholesterol in a human by 40-80% over a 24, 60 or 90 day period relative to predose levels, with little or no reduction in serum HDL cholesterol and/or with little or no measurable effect on liver function, as determined by ALT and AST measurements.","In one embodiment, the ligand of the invention comprises an antibody or antigen-binding fragment of an antibody that specifically binds hPCSK9 and is characterized by at least one of: (i) capable of reducing serum total cholesterol at least about 25-35% and sustaining the reduction over at least a 24 day period relative to a predose level, preferably the reduction in serum total cholesterol is at least about 30-40%; (ii) capable of reducing serum LDL cholesterol at least about 65-80% and sustaining the reduction over at least a 24 day period relative to a predose level; (iii) capable of reducing serum triglyceride at least about 25-40% relative to predose level; (iv) does not reduce serum HDL cholesterol or reduces serum HDL cholesterol no more than 5% relative to predose level.","See US2011/0065902 for definitions of these terms and optional features, the disclosure of which is incorporated herein by reference in its entirety.","In one embodiment, the invention comprises an antibody or antigen-binding fragment of an antibody that specifically binds hPCSK9 and is characterized by at least one of: (i) capable of reducing serum LDL cholesterol at least about 40-70% and sustaining the reduction over at least a 60 or 90 day period relative to a predose level; (ii) capable of reducing serum triglyceride at least about 25-40% relative to predose level; (iii) does not reduce serum HDL cholesterol or reduces serum HDL cholesterol no more than 5% relative to predose level.","In one embodiment, the antibody or antigen-binding fragment is characterized as exhibiting an enhanced binding affinity (KD) for hPCSK9 at pH 5.5 relative to the KD at pH 7.4, as measured by plasmon surface resonance.","In a specific embodiment, the antibody or fragment thereof exhibits at least a 20-fold, at least a 40-fold or at least a 50-fold enhanced affinity for PCSK9 at an acidic pH relative to a neutral pH, as measured by surface plasmon resonance.","In one embodiment, the antibody or antigen-binding fragment is characterized as not exhibiting an enhanced binding affinity for PCSK9 at an acidic pH relative to a neutral pH, as measured by surface plasmon resonance.","In a specific embodiment, the antibody or fragment thereof exhibits a decreased binding affinity at an acidic pH.","In another embodiment, the antibody or antigen-binding fragment binds human, human GOF mutation D374Y, cynomolgus monkey, rhesus monkey, mouse, rat and hamster PCSK9.In one embodiment, the antibody or antigen-binding fragment binds human and monkey PCSK9, but does not bind mouse, rat or hamster PCSK9.In one embodiment, the invention comprises an antibody or antigen-binding fragment of an antibody comprising one or more of a heavy chain variable region (HCVR), light chain variable region (LCVR), HCDR1, HCDR2, HCDR3 disclosed in any of paragraphs [023]-[037] of US2011/0065902, the disclosures of which are incorporated herein by reference.","In a related embodiment, the invention comprises an antibody or antigen-binding fragment of an antibody which specifically binds hPCSK9, wherein the antibody or fragment comprises heavy and light chain CDR domains contained within heavy and light chain sequence pairs selected from the group consisting of SEQ ID NO (using the sequence numbering in US2011/0065902): 2/10, 18/20, 22/24, 26/34, 42/44, 46/48, 50/58, 66/68, 70/72, 74/82, 90/92, 94/96, 98/106, 114/116, 118/120, 122/130, 138/140, 142/144, 146/154, 162/164, 166/168, 170/178, 186/188, 190/192, 194/202, 210/212, 214/216, 218/226, 234/236, 238/240, 242/250, 258/260, 262/264, 266/274, 282/284, 286/288, 290/298, 306/308, 310/312, 314/322, 330/332, 334/336, 338/346, 354/356, 358/360, 362/370, 378/380, 382/384, 386/394, 402/404, 406/408, 410/418, 426/428, 430/432, 434/442, 450/452, 454/456, 458/466, 474/476, 478/480, 482/490, 498/500, 502/504, 506/514, 522/524, 526/528, 530/538, 546/548, 550/552, 554/562, 570/572, 574/576, 578/586, 594/596, 598/600, 602/610, 618/620, 622/624, 626/634, 642/644, 646/648, 650/658, 666/668, 670/672, 674/682, 690/692, 694/696, 698/706, 714/716, 718/720, 722/730, 738/740 and 742/744.In one embodiment, the CDR sequences are contained within HCVR and LCVR selected from the amino acid sequence pairs of SEQ ID NO: 50/58, 66/68, 70/72, 74/82, 90/92, 94/96, 122/130, 138/140, 142/144, 218/226, 234/236, 238/240, 242/250, 258/260, 262/264, 314/322, 330/332 and 334/336.In more specific embodiments, the CDR sequences are comprised within HCVR/LCVR sequences selected from SEQ ID NO: 90/92 or 218/226.In an example, the invention features a pharmaceutical composition comprising a ligand of the invention, wherein the ligand comprises or consists of a recombinant human antibody or fragment thereof which specifically binds hPCSK9 and a pharmaceutically acceptable carrier.","In one embodiment, the invention features a composition which is a combination of a ligand of the invention (eg, an antibody or antigen-binding fragment of an antibody), and a second therapeutic agent.","The second therapeutic agent may be any agent that is advantageously combined with the ligand of the invention, for example, an agent capable of inducing a cellular depletion of cholesterol synthesis by inhibiting 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase, such as, for example, cerovastatin, atorvastatin, simvastatin, pitavastin, rosuvastatin, fluvastatin, lovastatin, pravastatin, etc; capable of inhibiting cholesterol uptake and or bile acid re-absorption; capable of increasing lipoprotein catabolism (such as niacin); and/or activators of the LXR transcription factor that plays a role in cholesterol elimination such as 22-hydroxycholesterol.","In an example, the invention provides a method for inhibiting hPCSK9 activity using the anti-PCSK9 ligand of the invention (eg, an antibody or antigen-binding portion of the antibody of the invention), wherein the therapeutic methods comprise administering a therapeutically effective amount of a pharmaceutical composition comprising an antibody or antigen-binding fragment of an antibody of the invention.","The disorder treated is any disease or condition which is improved, ameliorated, inhibited or prevented by removal, inhibition or reduction of PCSK9 activity.","Specific populations treatable by the therapeutic methods of the invention include subjects indicated for LDL apheresis, subjects with PCSK9-activating mutations (gain of function mutations, “GOF”), subjects with heterozygous Familial Hypercholesterolemia (heFH); subjects with primary hypercholesterolemia who are statin intolerant or statin uncontrolled; and subjects at risk for developing hypercholesterolemia who may be preventably treated.","Other indications include dyslipidemia associated with secondary causes such as Type 2 diabetes mellitus, cholestatic liver diseases (primary biliary cirrhosis), nephrotic syndrome, hypothyroidism, obesity; and the prevention and treatment of atherosclerosis and cardiovascular diseases.","In specific embodiments of the method of the invention, the ligand of the invention (eg, anti-hPCSK9 antibody or antibody fragment of the invention) is useful to reduce elevated total cholesterol, non-HDL cholesterol, LDL cholesterol, and/or apolipoprotein B (apolipoprotein B100).","The ligand (eg, antibody or antigen-binding fragment) of the invention may be used alone or in combination with a second agent, for example, an HMG-CoA reductase inhibitor and/or another lipid lowering drug.","Treatment Population The invention provides therapeutic methods for treating a human patient in need of a composition or ligand of the invention.","While modifications in lifestyle and conventional drug treatment are often successful in reducing cholesterol levels, not all patients are able to achieve the recommended target cholesterol levels with such approaches.","Various conditions, such as familial hypercholesterolemia (FH), appear to be resistant to lowering of LDL-C levels in spite of aggressive use of conventional therapy.","Homozygous and heterozygous familial hypercholesterolemia (hoFH, heFH) is a condition associated with premature atherosclerotic vascular disease.","However, patients diagnosed with hoFH are largely unresponsive to conventional drug therapy and have limited treatment options.","Specifically, treatment with statins, which reduce LDL-C by inhibiting cholesterol synthesis and upregulating the hepatic LDL receptor, may have little effect in patients whose LDL receptors are non-existent or defective.","A mean LDL-C reduction of only less than about 20% has been recently reported in patients with genotype-confirmed hoFH treated with the maximal dose of statins.","The addition of ezetimibe 10 mg/day to this regimen resulted in a total reduction of LDL-C levels of 27%, which is still far from optimal.","Likewise, many patients are statin non-responsive, poorly controlled with statin therapy, or cannot tolerate statin therapy; in general, these patients are unable to achieve cholesterol control with alternative treatments.","There is a large unmet medical need for new treatments that can address the short-comings of current treatment options.","Specific populations treatable by the therapeutic methods of the invention include patients indicated for LDL apheresis, subjects with PCSK9-activating (GOF) mutations, heterozygous Familial Hypercholesterolemia (heFH); subjects with primary hypercholesterolemia who are statin intolerant or statin uncontrolled; and subjects at risk for developing hypercholesterolemia who may be preventably treated.","Therapeutic Administration and Formulations The invention provides therapeutic compositions comprising the anti-PCSK9 ligands, antibodies or antigen-binding fragments thereof of the present invention.","The administration of therapeutic compositions in accordance with the invention will be administered with suitable carriers, excipients, and other agents that are incorporated into formulations to provide improved transfer, delivery, tolerance, and the like.","A multitude of appropriate formulations can be found in the formulary known to all pharmaceutical chemists: Remington's Pharmaceutical Sciences, Mack Publishing Company, Easton, Pa.","These formulations include, for example, powders, pastes, ointments, jellies, waxes, oils, lipids, lipid (cationic or anionic) containing vesicles (such as LIPOFECTINT™), DNA conjugates, anhydrous absorption pastes, oil-in-water and water-in-oil emulsions, emulsions carbowax (polyethylene glycols of various molecular weights), semi-solid gels, and semi-solid mixtures containing carbowax.","See also Powell et al.","“Compendium of excipients for parenteral formulations” PDA (1998) J Pharm Sci Technol 52:238-311.The dose may vary depending upon the age and the size of a subject to be administered, target disease, conditions, route of administration, and the like.","When the ligand, eg, antibody, of the present invention is used for treating various conditions and diseases associated with PCSK9, including hypercholesterolemia, disorders associated with LDL and apolipoprotein B, and lipid metabolism disorders, and the like, in an adult patient, it is advantageous to intravenously administer the ligand or antibody of the present invention normally at a single dose of about 0.01 to about 20 mg/kg body weight, more preferably about 0.02 to about 7, about 0.03 to about 5, or about 0.05 to about 3 mg/kg body weight.","Depending on the severity of the condition, the frequency and the duration of the treatment can be adjusted.","Various delivery systems are known and can be used to administer the pharmaceutical composition of the invention, thus the composition invention provides the ligand by e.g., encapsulation in liposomes, microparticles, microcapsules, recombinant cells capable of expressing the mutant viruses, receptor mediated endocytosis (see, e.g., Wu et al.","(1987) J. Biol.","Chem.","262:4429-4432).","Methods of introduction include, but are not limited to, intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal, epidural, and oral routes.","The composition may be administered by any convenient route, for example by infusion or bolus injection, by absorption through epithelial or mucocutaneous linings (e.g., oral mucosa, rectal and intestinal mucosa, etc.)","and may be administered together with other biologically active agents.","Administration can be systemic or local.","The pharmaceutical composition can be also delivered in a vesicle, in particular a liposome (see Langer (1990) Science 249:1527-1533; Treat et al.","(1989) in Liposomes in the Therapy of Infectious Disease and Cancer, Lopez Berestein and Fidler (eds.","), Liss, New York, pp.","353-365; Lopez-Berestein, ibid., pp.","317-327; see generally ibid.).","In certain situations, the pharmaceutical composition can be delivered in a controlled release system.","In one embodiment, a pump may be used (see Langer, supra; Sefton (1987) CRC Crit.","Ref Biomed.","Eng.","14:201).","In another embodiment, polymeric materials can be used; see, Medical Applications of Controlled Release, Langer and Wise (eds.","), CRC Pres., Boca Raton, Fla. (1974).","In yet another embodiment, a controlled release system can be placed in proximity of the composition's target, thus requiring only a fraction of the systemic dose (see, e.g., Goodson, in Medical Applications of Controlled Release, supra, vol.","2, pp.","115-138, 1984).","The injectable preparations may include dosage forms for intravenous, subcutaneous, intracutaneous and intramuscular injections, drip infusions, etc.","These injectable preparations may be prepared by methods publicly known.","For example, the injectable preparations may be prepared, e.g., by dissolving, suspending or emulsifying the antibody or its salt described above in a sterile aqueous medium or an oily medium conventionally used for injections.","As the aqueous medium for injections, there are, for example, physiological saline, an isotonic solution containing glucose and other auxiliary agents, etc., which may be used in combination with an appropriate solubilizing agent such as an alcohol (e.g., ethanol), a polyalcohol (e.g., propylene glycol, polyethylene glycol), a nonionic surfactant [e.g., polysorbate 80, HCO-50 (polyoxyethylene (50 mol) adduct of hydrogenated castor oil)], etc.","As the oily medium, there are employed, e.g., sesame oil, soybean oil, etc., which may be used in combination with a solubilizing agent such as benzyl benzoate, benzyl alcohol, etc.","The injection thus prepared is preferably filled in an appropriate ampoule.","A pharmaceutical composition of the present invention can be delivered subcutaneously or intravenously with a standard needle and syringe.","In addition, with respect to subcutaneous delivery, a pen delivery device readily has applications in delivering a pharmaceutical composition of the present invention.","Such a pen delivery device can be reusable or disposable.","A reusable pen delivery device generally utilizes a replaceable cartridge that contains a pharmaceutical composition.","Once all of the pharmaceutical composition within the cartridge has been administered and the cartridge is empty, the empty cartridge can readily be discarded and replaced with a new cartridge that contains the pharmaceutical composition.","The pen delivery device can then be reused.","In a disposable pen delivery device, there is no replaceable cartridge.","Rather, the disposable pen delivery device comes prefilled with the pharmaceutical composition held in a reservoir within the device.","Once the reservoir is emptied of the pharmaceutical composition, the entire device is discarded.","Numerous reusable pen and autoinjector delivery devices have applications in the subcutaneous delivery of a pharmaceutical composition of the present invention.","Examples include, but certainly are not limited to AUTOPEN™ (Owen Mumford, Inc., Woodstock, UK), DISETRONIC™ pen (Disetronic Medical Systems, Burghdorf, Switzerland), HUMALOG MIX 75/25™ pen, HUMALOG™ pen, HUMALIN 70/30™ pen (Eli Lilly and Co., Indianapolis, Ind.","), NOVOPEN™ I, II and III (Novo Nordisk, Copenhagen, Denmark), NOVOPEN JUNIOR™ (Novo Nordisk, Copenhagen, Denmark), BD™ pen (Becton Dickinson, Franklin Lakes, N.J.), OPTIPENT™, OPTIPEN PRO™, OPTIPEN STARLET™, and OPTICLIKT™ (sanofi-aventis, Frankfurt, Germany), to name only a few.","Examples of disposable pen delivery devices having applications in subcutaneous delivery of a pharmaceutical composition of the present invention include, but certainly are not limited to the SOLOSTAR™ pen (sanofi-aventis), the FLEXPEN™ (Novo Nordisk), and the KWIKPEN™ (Eli Lilly).","Advantageously, the pharmaceutical compositions for oral or parenteral use described above are prepared into dosage forms in a unit dose suited to fit a dose of the active ingredients.","Such dosage forms in a unit dose include, for example, tablets, pills, capsules, injections (ampoules), suppositories, etc.","The amount of the aforesaid antibody contained is generally about 5 to about 500 mg per dosage form in a unit dose; especially in the form of injection, it is preferred that the aforesaid antibody is contained in about 5 to about 100 mg and in about 10 to about 250 mg for the other dosage forms.","The invention provides therapeutic methods in which the ligand, eg, antibody or antibody fragment, of the invention is useful to treat hypercholesterolemia associated with a variety of conditions involving hPCSK9.The anti-PCSK9 ligands, eg, antibodies or antibody fragments, of the invention are particularly useful for the treatment of hypercholesterolemia and the like.","Combination therapies may include the anti-PCSK9 ligand of the invention with, for example, one or more of any agent that (1) induces a cellular depletion of cholesterol synthesis by inhibiting 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase, such as cerivastatin, atorvastatin, simvastatin, pitavastatin, rosuvastatin, fluvastatin, lovastatin, pravastatin; (2) inhibits cholesterol uptake and or bile acid re-absorption; (3) increase lipoprotein catabolism (such as niacin); and activators of the LXR transcription factor that plays a role in cholesterol elimination such as 22-hydroxycholesterol or fixed combinations such as ezetimibe plus simvastatin; a statin with a bile resin (e.g., cholestyramine, colestipol, colesevelam), a fixed combination of niacin plus a statin (e.g., niacin with lovastatin); or with other lipid lowering agents such as omega-3-fatty acid ethyl esters (for example, omacor).","Tailoring Antibodies to Rare PCSK9 Variant Profile As outline above, the invention includes the possibility to tailor treatment of humans further by selecting antibody-based ligands with variable domains based on gene segments commonly found in humans of the ethnic populations where the variant PCSK9 forms are found to meet the selection criteria of the invention.","An example is provided below for ligands comprising antibody VH domains derived from recombination of human VH3-23.The inventor analysed the frequencies and distribution of various human VH3-23 alleles and realised the desirability of using ligands based on human VH3-23 alleles comprising SNP rs56069819.This SNP corresponds to a change from leucine at position 24 in the encoded protein sequence to a valine at that position (L24V change) and the SNP is at coordinate 106268889 on human chromosome 14.FIG.","2 shows the cumulative allele frequency distribution across the 1000 Genomes Project database of human VH3-23 alleles comprising SNP rs56069819 (such alleles denoted “C” and the most frequent allele (which does not comprise this SNP) denoted “A”).","The figure shows that VH3-23 alleles comprising SNP rs56069819 are present at a cumulative frequency of 11% across all human ethnic populations taken as a whole, whereas in certain specific human ethnic sub-populations (ASW, LWK, YRI, CEU and GBR) such alleles are present at an above-average cumulative frequency.","Indicated in the figure are those human PCSK9 variant forms (marked “Variants”) that are found in the various sub-populations with above-average occurrence of human VH3-23 alleles comprising SNP rs56069819.Table 7 shows the VH3-23 variants and the SNPs that they comprise, as well as their cumulative allele frequencies as found in the 1000 Genomes Project database.","Notably, human VH3-23 alleles comprising SNP rs56069819 were found in the CEU population at a frequency that is almost double the frequency of 11% for all populations.","For the ASW and YRI populations the frequency was over a quarter of the population.","Thus, the invention advantageously enables one to select a ligand comprising an antibody or antibody fragment, wherein the antibody or fragment comprises a VH domain derived from the recombination of a human VH gene segment, a human D gene segment and a human JH gene segment, the VH gene segment comprising a nucleotide sequence that comprises SNP rs56069819 (dbSNP numbering, build number as recited above).","In an example, one can tailor the treatment further by selecting such a ligand that specifically binds to a human PCSK9 selected from forms: f, c, m, e, h, p, q and aj, such forms being those appearing in human populations ASW, LWK, YRI, CEU and GBR.","In an example, the VH gene segment is VH3-23*04, which is a commonly found variant that comprises SNP rs56069819 in human populations ASW, LWK, YRI, CEU and GBR.","In an example, the ligand is for treating and/or preventing a PCSK9-mediated disease or condition in a human that expresses a human PCSK9 selected from forms: f, c, m, e, h, p, q and aj.","In an example, the ligand is for treating and/or preventing a PCSK9-mediated disease or condition in a human of ASW, LWK, YRI, CEU or GBR ancestry.","In an embodiment, the ligand is for treating and/or preventing a PCSK9-mediated disease or condition in a human of ASW ancestry, wherein the human expresses a PCSK9 selected from f, c, m, e, h, p and q or the human comprises a corresponding nucleotide or amino acid sequence as set out in Table 6.Optionally this ligand comprises a VH domain derived from recombination of human VH3-23*04.In an embodiment, the ligand is for treating and/or preventing a PCSK9-mediated disease or condition in a human of LWK ancestry, wherein the human expresses a PCSK9 selected from f, c, m, e and h or the human comprises a corresponding nucleotide or amino acid sequence as set out in Table 6.Optionally this ligand comprises a VH domain derived from recombination of human VH3-23*04.In an embodiment, the ligand is for treating and/or preventing a PCSK9-mediated disease or condition in a human of YRI ancestry, wherein the human expresses a PCSK9 selected from f, c, m, e and h or the human comprises a corresponding nucleotide or amino acid sequence as set out in Table 6.Optionally this ligand comprises a VH domain derived from recombination of human VH3-23*04.In an embodiment, the ligand is for treating and/or preventing a PCSK9-mediated disease or condition in a human of CEU ancestry, wherein the human expresses a PCSK9 selected from f, c, p and aj or the human comprises a corresponding nucleotide or amino acid sequence as set out in Table 6.Optionally this ligand comprises a VH domain derived from recombination of human VH3-23*04.In an embodiment, the ligand is for treating and/or preventing a PCSK9-mediated disease or condition in a human of GBR ancestry, wherein the human expresses a PCSK9 selected from f c and p or the human comprises a corresponding nucleotide or amino acid sequence as set out in Table 6.Optionally this ligand comprises a VH domain derived from recombination of human VH3-23*04.In an example, the ligand is alirocumab.","In other embodiments, as explained more fully above, the invention provides for ligands which are tailored to the human recipient's genotype and/or phenotype based on alternative human VH gene segments, or on Vκ, Vλ or constant region gene segments (see further Table 9 for representative variants).","For example, the ligand of the invention comprises or consists of an antibody that comprises a VH domain that is derived from the recombination of a human VH gene segment, a human D gene segment and a human JH gene segment, wherein the VH gene segment is selected from the group consisting of (i) IGHV1-18*01 and the genome of the human comprises a human IGHV1-18*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGHV1-18*01; or (ii) IGVH1-46*01 and the genome of the human comprises a human IGHV1-46*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGHV1-46*01.For example, the ligand of the invention comprises or consists of an antibody that comprises a VL domain that is derived from the recombination of a human VL gene segment and a human JL gene segment, wherein the VL gene segment is selected from the group consisting of (i) IGKV4-1*01 and the genome of the human comprises a human IGKV4-1*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGKV4-1*01; (ii) IGLV2-14*01 and the genome of the human comprises a human IGLV2-14*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGLV2-14*01; or (iii) IGKV1-13*02 and the genome of the human comprises a human IGKV1-13*02 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGKV1-13*02.For example, the inventor identified the possibility of addressing the rarer IGH-gamma-1 SNPs 204D (observed cumulative frequency of 0.296) and 206L (observed cumulative frequency of 0.283) individually or in combination.","These residues are part of the CH3 domain, and as such they form part of antibody Fc regions.","Thus, matching of these CH3 variations with the patient is especially beneficial for reasons as discussed above.","Thus, in this example the ligand of the invention comprises or consists of an antibody that comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 or a Leu corresponding to position 206 of SEQ ID NO: 42 and wherein the genome of the human comprises a gamma-1 heavy chain constant region nucleotide sequence that encodes such an Asp or Leu or the human expresses antibodies comprising human gamma-1 constant regions comprising such an Asp or Leu.","An example of such a ligand is alirocumab.","In another example, the inventor identified the possibility of addressing IGH-gamma-2 SNPs.","This included consideration of Fc region variation—in this respect, the inventor focused on positions 161 and 257 which are in the Fc region.","Thus, in this example the ligand of the invention comprises or consists of an antibody that comprises a human gamma-2 heavy chain constant region that comprises an amino acid selected from the group consisting of a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44, a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44; and wherein the genome of the human comprises a gamma-2 heavy chain constant region nucleotide sequence that encodes such a selected amino acid or the human expresses antibodies comprising human gamma-2 constant regions comprising such a selected amino acid.","An example of such a ligand is evolocumab or bococizumab.","In another example, the inventor addressed human kappa constant region variation.","Thus, in this example the ligand of the invention comprises or consists of an antibody that comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 or a Cys corresponding to position 87 of SEQ ID NO: 50; and wherein the genome of the human comprises a kappa light chain constant region nucleotide sequence that encodes such a Val or Cys or the human expresses antibodies comprising human kappa light chain constant regions comprising such a Val or Cys.","An example of such a ligand is alirocumab or bococizumab.","In another example, the inventor addressed human lambda constant region variation.","Thus, in this example the ligand of the invention comprises or consists of an antibody that comprises a human IGLC2*01 light chain constant region; and wherein the genome of the human comprises a human IGLC2*01 nucleotide sequence or the human expresses antibodies comprising human light chain IGLC2*01 constant regions.","An example of such a ligand is evolocumab.","Further exemplary ligands are in the paragraphs 1-17 as follows.","1.An antibody or antibody fragment for use in a method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, wherein the antibody or fragment comprises a human gamma heavy chain constant region that comprises a first amino acid that is encoded by a human gamma heavy chain constant region gene segment SNP, and the antibody or fragment specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) amino acid sequence that comprises a C-terminal domain comprising a mutation I474V or E670G in SEQ ID NO: 1, wherein the human comprises a nucleotide sequence encoding said PCSK9 amino acid sequence and comprises a human gamma heavy chain constant region gene segment comprising said SNP, or the human expresses antibodies comprising human gamma constant regions comprising said first amino acid.","In an alternative, paragraph 1 provides:— An antibody or antibody fragment for use in a method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, wherein the antibody or fragment comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 or a Leu corresponding to position 206 of SEQ ID NO: 42, and the antibody or fragment specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) amino acid sequence that comprises a C-terminal domain comprising a mutation I474V or E670G in SEQ ID NO: 1, wherein the human comprises a nucleotide sequence encoding said amino acid sequence and comprises an IGHG1*01 human heavy chain constant region gene segment, or the human expresses antibodies comprising human gamma-1 constant regions comprising such an Asp and Leu.","In an embodiment, said mutation is I474V.","In another embodiment, said mutation is E670G.","An example provides:— An antibody or antibody fragment for use in a method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, wherein the antibody or fragment comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 and a Leu corresponding to position 206 of SEQ ID NO: 42, and the antibody or fragment specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) amino acid sequence that comprises a C-terminal domain comprising a mutation I474V in SEQ ID NO: 1, wherein the human comprises a nucleotide sequence encoding said amino acid sequence and comprises an IGHG1*01 human heavy chain constant region gene segment.","Optionally, the antibody or fragment comprises an IGHG1*01 human heavy chain constant region.","Another example provides:— An antibody or antibody fragment for use in a method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, wherein the antibody or fragment comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 and a Leu corresponding to position 206 of SEQ ID NO: 42, and the antibody or fragment specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) amino acid sequence that comprises a C-terminal domain comprising a mutation E670G in SEQ ID NO: 1, wherein the human comprises a nucleotide sequence encoding said amino acid sequence and comprises an IGHG1*01 human heavy chain constant region gene segment.","Optionally, the antibody or fragment comprises an IGHG1*01 human heavy chain constant region.","In an example, said antibody or antibody fragment has been determined to specifically bind a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 or E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 and a Leu corresponding to position 206 of SEQ ID NO: 42 and wherein said human comprises (i) an IGHG1*01 human heavy chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.2.The antibody or antibody fragment of paragraph 1, wherein the antibody comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 and a Leu corresponding to position 206 of SEQ ID NO: 42.3.The antibody or antibody fragment of paragraph 1 or 2, wherein the antibody comprises an IGHG1*01 human heavy chain constant region.","4.The antibody or antibody fragment of any one of paragraphs 1 to 3, wherein the human has been determined to comprise the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1 and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein encoded by the nucleotide sequence of SEQ ID NO: 29 or 30.5.The antibody or antibody fragment of any one of paragraphs 1 to 4, the method comprising the step of determining that the human comprises the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein comprising said mutation I474V or E670G, optionally, wherein the determining step is performed before administration of the antibody to the human.","6.The antibody or antibody fragment of paragraph 5, wherein the step of determining comprises assaying a biological sample from the human for a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.7.The antibody or antibody fragment of paragraph 6, wherein the assaying comprises contacting the biological sample with a. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides that can specifically hybridize to and identify in the biological sample a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or that specifically hybridizes to an antisense of said sequence, wherein said nucleic acid hybridizes to at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 or hybridizes to an antisense sequence thereby forming a complex when at least one nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and/or b. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides of a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or comprising an antisense sequence of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 thereby forming a complex when the nucleotide sequence encoding the PCSK9 that comprises a C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and detecting the presence or absence of the complex, wherein detecting the presence of the complex determines that the human comprises the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.8.The antibody or antibody fragment of paragraph 6 or 7, wherein the assaying comprises nucleic acid amplification and optionally one or more methods selected from sequencing, next generation sequencing, nucleic acid hybridization, and allele-specific amplification and/or wherein the assaying is performed in a multiplex format.","9.The antibody or antibody fragment of any one of paragraphs 1 to 8, wherein said antibody or antibody fragment is for administration to a human that is or has been further determined to be substantially resistant to statin treatment.","10.The antibody or antibody fragment of any one of paragraphs 1 to 9, wherein antibody or antibody fragment is for administration to a human that is receiving or has received statin treatment or has reduced responsiveness to statin treatment.","11.The antibody or antibody fragment of paragraph 9 or 10, wherein said antibody or antibody fragment is for administration to the human separately or simultaneously with said statin treatment.","12.The antibody or antibody fragment of any one of paragraphs 6 to 10, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine and/or saliva of said human.","13.The antibody or antibody fragment of any one of paragraphs 1 to 12, wherein said human is indicated as heterozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising a mutation I474V or E670G, optionally, wherein said human is further indicated as comprising the nucleotide sequence of SEQ ID NO: 28, or said human is indicated as homozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising a mutation I474V or E670G in SEQ ID NO: 1.14.The antibody or antibody fragment of any one of paragraphs 1 to 13, wherein said human has been diagnosed with at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.","15.The antibody or antibody fragment of any one of paragraphs 1 to 14, wherein said antibody or antibody fragment treats or reduces the risk in said human of at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.","16.The antibody or antibody fragment of any one of paragraphs 1 to 15, wherein the nucleotide sequence is SEQ ID NO: 29 or 30.17.The antibody or antibody fragment of any one of paragraphs 1 to 16, wherein said antibody or antibody fragment is for administration by intravenous or subcutaneous administration and/or is comprised in an injectable preparation.","Further exemplary methods are in the paragraphs 1-18 as follows.","1.A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 or E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 or a Leu corresponding to position 206 of SEQ ID NO: 42 and wherein said human comprises (i) an IGHG1*01 human heavy chain constant region gene segment, or the human expresses antibodies comprising human gamma-1 heavy chain constant regions comprising such an Asp and Leu and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.In an embodiment, said mutation is I474V.","In another embodiment, said mutation is E670G.","An example provides:— A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 in SEQ ID NO: 1, wherein the antibody or fragment comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 and a Leu corresponding to position 206 of SEQ ID NO: 42 and wherein said human comprises (i) an IGHG1*01 human heavy chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V in SEQ ID NO: 1.Optionally, the antibody or fragment comprises a IGHG1*01 human heavy chain constant region.","Another example provides:— A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 and a Leu corresponding to position 206 of SEQ ID NO: 42 and wherein said human comprises (i) an IGHG1*01 human heavy chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation E670G in SEQ ID NO: 1.Optionally, the antibody or fragment comprises an IGHG1*01 human heavy chain constant region.","In an example, said antibody or antibody fragment has been determined to specifically bind a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 or E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 and a Leu corresponding to position 206 of SEQ ID NO: 42 and wherein said human comprises (i) an IGHG1*01 human heavy chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.2.The method of paragraph 1, comprising, before said administering, selecting a human comprising said nucleotide sequence of (ii), wherein the human is the human of paragraph 1.3.The method of paragraph 1 or 2, wherein the antibody comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 and a Leu corresponding to position 206 of SEQ ID NO: 42.4.The method of paragraph 1, 2 or 3, wherein the antibody comprises an IGHG1*01 human heavy chain constant region.","5.The method of any one of paragraphs 1 to 4, wherein the human has been determined to comprise the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1 and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein encoded by the nucleotide sequence of SEQ ID NO: 29 or 30.6.The method of any one of paragraphs 1 to 5, comprising the step of determining that the human comprises the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein comprising said mutation I474V or E670G, optionally, wherein the determining step is performed before administration of the antibody to the human.","7.The method of paragraph 6, wherein the step of determining comprises assaying a biological sample from the human for a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.8.The method of paragraph 7, wherein the assaying comprises contacting the biological sample with a. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides that can specifically hybridize to and identify in the biological sample a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or that specifically hybridizes to an antisense of said sequence, wherein said nucleic acid hybridizes to at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 or hybridizes to an antisense sequence thereby forming a complex when at least one nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and/or b. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides of a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or comprising an antisense sequence of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 thereby forming a complex when the nucleotide sequence encoding the PCSK9 that comprises a C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and detecting the presence or absence of the complex, wherein detecting the presence of the complex determines that the human comprises the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.9.The method of paragraph 7 or 8, wherein the assaying comprises nucleic acid amplification and optionally one or more methods selected from sequencing, next generation sequencing, nucleic acid hybridization, and allele-specific amplification and/or wherein the assaying is performed in a multiplex format.","10.The method of any one of paragraphs 1 to 9, wherein said human is or has been further determined to be substantially resistant to statin treatment.","11.The method of any one of paragraphs 1 to 10, wherein said human is receiving or has received statin treatment or has reduced responsiveness to statin treatment.","12.The method of paragraph 10 or 11, wherein said antibody or antibody fragment is administered to the human separately or simultaneously with said statin treatment.","13.The method of any one of paragraphs 7 to 9, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine and/or saliva of said human.","14.The method of any one of paragraphs 1 to 13, wherein said human is indicated as heterozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising said mutation I474V or E670G, optionally, wherein said human is further indicated as comprising the nucleotide sequence of SEQ ID NO: 28, or said human is indicated as homozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.15.The method of any one of paragraphs 1 to 14, wherein said human has been diagnosed with at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.","16.The method of any one of paragraphs 1 to 15, wherein said antibody or antibody fragment treats or reduces the risk in said human of at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.","17.The method of any one of paragraphs 1 to 16, wherein the nucleotide sequence is SEQ ID NO: 29 or 30.18.The method of any one of paragraphs 1 to 17, wherein said antibody or antibody fragment is administered by intravenous or subcutaneous administration and/or is comprised in an injectable preparation.","Further exemplary ligands are in the paragraphs 1-17 as follows.","1.An antibody or antibody fragment for use in a method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, wherein the antibody comprises a human gamma-2 heavy chain constant region that comprises an amino acid selected from the group consisting of a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44, a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44, and the antibody or fragment specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) amino acid sequence that comprises a C-terminal domain comprising a mutation I474V or E670G in SEQ ID NO: 1, wherein the human comprises a nucleotide sequence encoding said amino acid sequence and comprises an IGHG2*01 human heavy chain constant region gene segment, or the human expresses antibodies comprising human gamma-2 constant regions comprising such a Pro, Asn, Phe, Val and Ala.","In an embodiment, said mutation is I474V.","In another embodiment, said mutation is E670G.","An example provides:— An antibody or antibody fragment for use in a method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, wherein the antibody comprises a human gamma-2 heavy chain constant region that comprises a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44, a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44, and the antibody or fragment specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) amino acid sequence that comprises a C-terminal domain comprising a mutation I474V in SEQ ID NO: 1, wherein the human comprises a nucleotide sequence encoding said amino acid sequence and comprises an IGHG2*01 human heavy chain constant region gene segment.","Optionally, the antibody or fragment comprises an IGHG2*01 human heavy chain constant region.","Another example provides:— An antibody or antibody fragment for use in a method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, wherein the antibody comprises a human gamma-2 heavy chain constant region that comprises a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44, a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44, and the antibody or fragment specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) amino acid sequence that comprises a C-terminal domain comprising a mutation E670G in SEQ ID NO: 1, wherein the human comprises a nucleotide sequence encoding said amino acid sequence and comprises an IGHG2*01 human heavy chain constant region gene segment.","Optionally, the antibody or fragment comprises an IGHG2*01 human heavy chain constant region.","In an example, said antibody or antibody fragment has been determined to specifically bind a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 or E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human gamma-2 heavy chain constant region that comprises a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44, a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44 and wherein said human comprises (i) an IGHG2*01 human heavy chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.2.The antibody or antibody fragment of paragraph 1, wherein the antibody comprises a human gamma-2 heavy chain constant region that comprises a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44, a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44.3.The antibody or antibody fragment of paragraph 1 or 2, wherein the antibody comprises an IGHG2*01 human heavy chain constant region.","4.The antibody or antibody fragment of any one of paragraphs 1 to 3, wherein the human has been determined to comprise the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1 and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein encoded by the nucleotide sequence of SEQ ID NO: 29 or 30.5.The antibody or antibody fragment of any one of paragraphs 1 to 4, the method comprising the step of determining that the human comprises the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein comprising said mutation I474V or E670G, optionally, wherein the determining step is performed before administration of the antibody to the human.","6.The antibody or antibody fragment of paragraph 5, wherein the step of determining comprises assaying a biological sample from the human for a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.7.The antibody or antibody fragment of paragraph 6, wherein the assaying comprises contacting the biological sample with a. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides that can specifically hybridize to and identify in the biological sample a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or that specifically hybridizes to an antisense of said sequence, wherein said nucleic acid hybridizes to at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 or hybridizes to an antisense sequence thereby forming a complex when at least one nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and/or b. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides of a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or comprising an antisense sequence of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 thereby forming a complex when the nucleotide sequence encoding the PCSK9 that comprises a C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and detecting the presence or absence of the complex, wherein detecting the presence of the complex determines that the human comprises the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.8.The antibody or antibody fragment of paragraph 6 or 7, wherein the assaying comprises nucleic acid amplification and optionally one or more methods selected from sequencing, next generation sequencing, nucleic acid hybridization, and allele-specific amplification and/or wherein the assaying is performed in a multiplex format.","9.The antibody or antibody fragment of any one of paragraphs 1 to 8, wherein said antibody or antibody fragment is for administration to a human that is or has been further determined to be substantially resistant to statin treatment.","10.The antibody or antibody fragment of any one of paragraphs 1 to 9, wherein antibody or antibody fragment is for administration to a human that is receiving or has received statin treatment or has reduced responsiveness to statin treatment.","11.The antibody or antibody fragment of paragraph 9 or 10, wherein said antibody or antibody fragment is for administration to the human separately or simultaneously with said statin treatment.","12.The antibody or antibody fragment of any one of paragraphs 6 to 8, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine and/or saliva of said human.","13.The antibody or antibody fragment of any one of paragraphs 1 to 12, wherein said human is indicated as heterozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising a mutation I474V or E670G, optionally, wherein said human is further indicated as comprising the nucleotide sequence of SEQ ID NO: 28, or said human is indicated as homozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising a mutation I474V or E670G in SEQ ID NO: 1.14.The antibody or antibody fragment of any one of paragraphs 1 to 13, wherein said human has been diagnosed with at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.","15.The antibody or antibody fragment of any one of paragraphs 1 to 14, wherein said antibody or antibody fragment treats or reduces the risk in said human of at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.","16.The antibody or antibody fragment of any one of paragraphs 1 to 15, wherein the nucleotide sequence is SEQ ID NO: 29 or 30.17.The antibody or antibody fragment of any one of paragraphs 1 to 16, wherein said antibody or antibody fragment is for administration by intravenous or subcutaneous administration and/or is comprised in an injectable preparation.","Further exemplary methods are in the paragraphs 1-18 as follows.","1.A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 or E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human gamma-2 heavy chain constant region that comprises an amino acid selected from the group consisting of a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44, a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44 and wherein said human comprises (i) an IGHG2*01 human heavy chain constant region gene segment, or the human expresses antibodies comprising human gamma-2 heavy chain constant regions comprising such a Pro, Asn, Phe, Val and Ala and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.In an embodiment, said mutation is I474V.","In another embodiment, said mutation is E670G.","An example provides:— A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 in SEQ ID NO: 1, wherein the antibody or fragment comprises a human gamma-2 heavy chain constant region that comprises a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44, a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44 and wherein said human comprises (i) an IGHG2*01 human heavy chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V in SEQ ID NO: 1.Optionally, the antibody or fragment comprises an IGHG2*01 human heavy chain constant region.","Another example provides:— A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human gamma-2 heavy chain constant region that comprises a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44, a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44 and wherein said human comprises (i) an IGHG2*01 human heavy chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation E670G in SEQ ID NO: 1.Optionally, the antibody or fragment comprises an IGHG2*01 human heavy chain constant region.","In an example, said antibody or antibody fragment has been determined to specifically bind a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 or E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human gamma-2 heavy chain constant region that comprises a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44, a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44 and wherein said human comprises (i) an IGHG2*01 human heavy chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.2.The method of paragraph 1, comprising, before said administering, selecting said human comprising said nucleotide sequence of (ii).","3.The method of paragraph 1 or 2, wherein the antibody comprises a human gamma-1 heavy chain constant region that comprises a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44, a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44.4.The method of paragraph 1, 2 or 3, wherein the antibody comprises an IGHG2*01 human heavy chain constant region.","5.The method of any one of paragraphs 1 to 4, wherein the human has been determined to comprise the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1 and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein encoded by the nucleotide sequence of SEQ ID NO: 29 or 30.6.The method of any one of paragraphs 1 to 5, comprising the step of determining that the human comprises the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein comprising said mutation I474V or E670G, optionally, wherein the determining step is performed before administration of the antibody to the human.","7.The method of paragraph 6, wherein the step of determining comprises assaying a biological sample from the human for a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.8.The method of paragraph 7, wherein the assaying comprises contacting the biological sample with a. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides that can specifically hybridize to and identify in the biological sample a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or that specifically hybridizes to an antisense of said sequence, wherein said nucleic acid hybridizes to at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 or hybridizes to an antisense sequence thereby forming a complex when at least one nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and/or b. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides of a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or comprising an antisense sequence of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 thereby forming a complex when the nucleotide sequence encoding the PCSK9 that comprises a C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and detecting the presence or absence of the complex, wherein detecting the presence of the complex determines that the human comprises the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.9.The method of paragraph 7 or 8, wherein the assaying comprises nucleic acid amplification and optionally one or more methods selected from sequencing, next generation sequencing, nucleic acid hybridization, and allele-specific amplification and/or wherein the assaying is performed in a multiplex format.","10.The method of any one of paragraphs 1 to 9, wherein said human is or has been further determined to be substantially resistant to statin treatment.","11.The method of any one of paragraphs 1 to 10, wherein said human is receiving or has received statin treatment or has reduced responsiveness to statin treatment.","12.The method of paragraph 10 or 11, wherein said antibody or antibody fragment is administered to the human separately or simultaneously with said statin treatment.","13.The method of any one of paragraphs 7 to 9, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine and/or saliva of said human.","14.The method of any one of paragraphs 1 to 13, wherein said human is indicated as heterozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising said mutation I474V or E670G, optionally, wherein said human is further indicated as comprising the nucleotide sequence of SEQ ID NO: 28, or said human is indicated as homozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.15.The method of any one of paragraphs 1 to 14, wherein said human has been diagnosed with at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.","16.The method of any one of paragraphs 1 to 15, wherein said antibody or antibody fragment treats or reduces the risk in said human of at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.","17.The method of any one of paragraphs 1 to 16, wherein the nucleotide sequence is SEQ ID NO: 29 or 30.18.The method of any one of paragraphs 1 to 17, wherein said antibody or antibody fragment is administered by intravenous or subcutaneous administration and/or is comprised in an injectable preparation.","Further exemplary ligands are in the paragraphs 1-17 as follows.","1.An antibody or antibody fragment for use in a method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, wherein the antibody or fragment comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 or a Cys corresponding to position 87 of SEQ ID NO: 50, and the antibody or fragment specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) amino acid sequence that comprises a C-terminal domain comprising a mutation I474V or E670G in SEQ ID NO: 1, wherein the human comprises a nucleotide sequence encoding said amino acid sequence and comprises an IGKC*01 human light chain constant region gene segment, or the human expresses antibodies comprising human kappa light chain constant regions comprising such an Val and Cys.","In an embodiment, said mutation is I474V.","In another embodiment, said mutation is E670G.","An example provides:— An antibody or antibody fragment for use in a method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, wherein the antibody or fragment comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 and a Cys corresponding to position 87 of SEQ ID NO: 50, and the antibody or fragment specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) amino acid sequence that comprises a C-terminal domain comprising a mutation I474V in SEQ ID NO: 1, wherein the human comprises a nucleotide sequence encoding said amino acid sequence and comprises an IGKC*01 human light chain constant region gene segment.","Optionally, the antibody or fragment comprises an IGKC*01 human light chain constant region.","Another example provides:— An antibody or antibody fragment for use in a method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, wherein the antibody or fragment comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 and a Cys corresponding to position 87 of SEQ ID NO: 50, and the antibody or fragment specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) amino acid sequence that comprises a C-terminal domain comprising a mutation E670G in SEQ ID NO: 1, wherein the human comprises a nucleotide sequence encoding said amino acid sequence and comprises an IGKC*01 human light chain constant region gene segment.","Optionally, the antibody or fragment comprises an IGKC*01 human light chain constant region.","In an example, said antibody or antibody fragment has been determined to specifically bind a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 or E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 and a Cys corresponding to position 87 of SEQ ID NO: 50 and wherein said human comprises (i) an IGKC*01 human heavy chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.2.The antibody or antibody fragment of paragraph 1, wherein the antibody comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 or a Cys corresponding to position 87 of SEQ ID NO: 50.3.The antibody or antibody fragment of paragraph 1 or 2, wherein the antibody comprises an IGKC*01 human kappa chain constant region.","4.The antibody or antibody fragment of any one of paragraphs 1 to 3, wherein the human has been determined to comprise the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1 and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein encoded by the nucleotide sequence of SEQ ID NO: 29 or 30.5.The antibody or antibody fragment of any one of paragraphs 1 to 4, the method comprising the step of determining that the human comprises the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein comprising said mutation I474V or E670G, optionally, wherein the determining step is performed before administration of the antibody to the human.","6.The antibody or antibody fragment of paragraph 5, wherein the step of determining comprises assaying a biological sample from the human for a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.7.The antibody or antibody fragment of paragraph 6, wherein the assaying comprises contacting the biological sample with a. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides that can specifically hybridize to and identify in the biological sample a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or that specifically hybridizes to an antisense of said sequence, wherein said nucleic acid hybridizes to at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 or hybridizes to an antisense sequence thereby forming a complex when at least one nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and/or b. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides of a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or comprising an antisense sequence of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 thereby forming a complex when the nucleotide sequence encoding the PCSK9 that comprises a C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and detecting the presence or absence of the complex, wherein detecting the presence of the complex determines that the human comprises the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.8.The antibody or antibody fragment of paragraph 6 or 7, wherein the assaying comprises nucleic acid amplification and optionally one or more methods selected from sequencing, next generation sequencing, nucleic acid hybridization, and allele-specific amplification and/or wherein the assaying is performed in a multiplex format.","9.The antibody or antibody fragment of any one of paragraphs 1 to 8, wherein said antibody or antibody fragment is for administration to a human that is or has been further determined to be substantially resistant to statin treatment.","10.The antibody or antibody fragment of any one of paragraphs 1 to 9, wherein antibody or antibody fragment is for administration to a human that is receiving or has received statin treatment or has reduced responsiveness to statin treatment.","11.The antibody or antibody fragment of paragraph 9 or 10, wherein said antibody or antibody fragment is for administration to the human separately or simultaneously with said statin treatment.","12.The antibody or antibody fragment of any one of paragraphs 6 to 10, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine and/or saliva of said human.","13.The antibody or antibody fragment of any one of paragraphs 1 to 12, wherein said human is indicated as heterozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising a mutation I474V or E670G, optionally, wherein said human is further indicated as comprising the nucleotide sequence of SEQ ID NO: 28, or said human is indicated as homozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising a mutation I474V or E670G in SEQ ID NO: 1.14.The antibody or antibody fragment of any one of paragraphs 1 to 13, wherein said human has been diagnosed with at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.","15.The antibody or antibody fragment of any one of paragraphs 1 to 14, wherein said antibody or antibody fragment treats or reduces the risk in said human of at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.","16.The antibody or antibody fragment of any one of paragraphs 1 to 15, wherein the nucleotide sequence is SEQ ID NO: 29 or 30.17.The antibody or antibody fragment of any one of paragraphs 1 to 16, wherein said antibody or antibody fragment is for administration by intravenous or subcutaneous administration and/or is comprised in an injectable preparation.","Further exemplary methods are in the paragraphs 1-18 as follows.","1.A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 or E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 or a Cys corresponding to position 87 of SEQ ID NO: 50 and wherein said human comprises (i) an IGKC*01 human light chain constant region gene segment, or the human expresses antibodies comprising human kappa light chain constant regions comprising such an Val and Cys and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.In an embodiment, said mutation is I474V.","In another embodiment, said mutation is E670G.","An example provides:— A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 in SEQ ID NO: 1, wherein the antibody or fragment comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 and a Cys corresponding to position 87 of SEQ ID NO: 50 and wherein said human comprises (i) an IGKC*01 human light chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V in SEQ ID NO: 1.Optionally, the antibody or fragment comprises an IGKC*01 human light chain constant region.","Another example provides:— A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 and a Cys corresponding to position 87 of SEQ ID NO: 50 and wherein said human comprises (i) an IGKC*01 human light chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation E670G in SEQ ID NO: 1.Optionally, the antibody or fragment comprises an IGKC*01 human light chain constant region.","In an example, said antibody or antibody fragment has been determined to specifically bind a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 or E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 and a Cys corresponding to position 87 of SEQ ID NO: 50 and wherein said human comprises (i) an IGKC*01 human heavy chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.2.The method of paragraph 1, comprising, before said administering, selecting said human comprising said nucleotide sequence of (ii).","3.The method of paragraph 1 or 2, wherein the antibody comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 or a Cys corresponding to position 87 of SEQ ID NO: 50.4.The method of paragraph 1, 2 or 3, wherein the antibody comprises an IGKC*01 human kappa chain constant region.","5.The method of any one of paragraphs 1 to 4, wherein the human has been determined to comprise the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1 and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein encoded by the nucleotide sequence of SEQ ID NO: 29 or 30.6.The method of any one of paragraphs 1 to 5, comprising the step of determining that the human comprises the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein comprising said mutation I474V or E670G, optionally, wherein the determining step is performed before administration of the antibody to the human.","7.The method of paragraph 6, wherein the step of determining comprises assaying a biological sample from the human for a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.8.The method of paragraph 7, wherein the assaying comprises contacting the biological sample with a. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides that can specifically hybridize to and identify in the biological sample a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or that specifically hybridizes to an antisense of said sequence, wherein said nucleic acid hybridizes to at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 or hybridizes to an antisense sequence thereby forming a complex when at least one nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and/or b. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides of a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or comprising an antisense sequence of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 thereby forming a complex when the nucleotide sequence encoding the PCSK9 that comprises a C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and detecting the presence or absence of the complex, wherein detecting the presence of the complex determines that the human comprises the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.9.The method of paragraph 7 or 8, wherein the assaying comprises nucleic acid amplification and optionally one or more methods selected from sequencing, next generation sequencing, nucleic acid hybridization, and allele-specific amplification and/or wherein the assaying is performed in a multiplex format.","10.The method of any one of paragraphs 1 to 9, wherein said human is or has been further determined to be substantially resistant to statin treatment.","11.The method of any one of paragraphs 1 to 10, wherein said human is receiving or has received statin treatment or has reduced responsiveness to statin treatment.","12.The method of paragraph 10 or 11, wherein said antibody or antibody fragment is administered to the human separately or simultaneously with said statin treatment.","13.The method of any one of paragraphs 7 to 9, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine and/or saliva of said human.","14.The method of any one of paragraphs 1 to 13, wherein said human is indicated as heterozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising said mutation I474V or E670G, optionally, wherein said human is further indicated as comprising the nucleotide sequence of SEQ ID NO: 28, or said human is indicated as homozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.15.The method of any one of paragraphs 1 to 14, wherein said human has been diagnosed with at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.","16.The method of any one of paragraphs 1 to 15, wherein said antibody or antibody fragment treats or reduces the risk in said human of at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.","17.The method of any one of paragraphs 1 to 16, wherein the nucleotide sequence is SEQ ID NO: 29 or 30.18.The method of any one of paragraphs 1 to 17, wherein said antibody or antibody fragment is administered by intravenous or subcutaneous administration and/or is comprised in an injectable preparation.","Further exemplary ligands are in the paragraphs 1-15 as follows.","1.An antibody or antibody fragment for use in a method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, wherein the antibody or fragment comprises a human IGLC2*01 lambda light chain constant region, and the antibody or fragment specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) amino acid sequence that comprises a C-terminal domain comprising a mutation I474V or E670G in SEQ ID NO: 1, wherein the human comprises a nucleotide sequence encoding said amino acid sequence and comprises a human IGLC2*01 lambda light chain constant region gene segment, or the human expresses antibodies comprising human IGLC2*01 lambda light chain constant regions.","In an embodiment, said mutation is I474V.","In another embodiment, said mutation is E670G.","An example provides:— An antibody or antibody fragment for use in a method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, wherein the antibody or fragment comprises a human IGLC2*01 lambda light chain constant region, and the antibody or fragment specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) amino acid sequence that comprises a C-terminal domain comprising a mutation I474V in SEQ ID NO: 1, wherein the human comprises a nucleotide sequence encoding said amino acid sequence and comprises a human IGLC2*01 lambda light chain constant region gene segment.","Optionally, the antibody or fragment comprises a human IGLC2*01 lambda light chain constant region.","Another example provides:— An antibody or antibody fragment for use in a method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, wherein the antibody or fragment comprises a human IGLC2*01 lambda light chain constant region, and the antibody or fragment specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) amino acid sequence that comprises a C-terminal domain comprising a mutation E670G in SEQ ID NO: 1, wherein the human comprises a nucleotide sequence encoding said amino acid sequence and comprises a human IGLC2*01 lambda light chain constant region gene segment.","Optionally, the antibody or fragment comprises a human IGLC2*01 lambda light chain constant region.","In an example, said antibody or antibody fragment has been determined to specifically bind a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 or E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human IGLC2*01 lambda light chain constant region and wherein said human comprises (i) an IGLC2*01 human heavy chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.2.The antibody or antibody fragment of paragraph 1, wherein the human has been determined to comprise the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1 and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein encoded by the nucleotide sequence of SEQ ID NO: 29 or 30.3.The antibody or antibody fragment of paragraphs 1 or 2, the method comprising the step of determining that the human comprises the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein comprising said mutation I474V or E670G, optionally, wherein the determining step is performed before administration of the antibody to the human.","4.The antibody or antibody fragment of paragraph 3, wherein the step of determining comprises assaying a biological sample from the human for a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.5.The antibody or antibody fragment of paragraph 4, wherein the assaying comprises contacting the biological sample with a. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides that can specifically hybridize to and identify in the biological sample a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or that specifically hybridizes to an antisense of said sequence, wherein said nucleic acid hybridizes to at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 or hybridizes to an antisense sequence thereby forming a complex when at least one nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and/or b. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides of a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or comprising an antisense sequence of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 thereby forming a complex when the nucleotide sequence encoding the PCSK9 that comprises a C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and detecting the presence or absence of the complex, wherein detecting the presence of the complex determines that the human comprises the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.6.The antibody or antibody fragment of paragraph 4 or 5, wherein the assaying comprises nucleic acid amplification and optionally one or more methods selected from sequencing, next generation sequencing, nucleic acid hybridization, and allele-specific amplification and/or wherein the assaying is performed in a multiplex format.","7.The antibody or antibody fragment of any one of paragraphs 1 to 6, wherein said antibody or antibody fragment is for administration to a human that is or has been further determined to be substantially resistant to statin treatment.","8.The antibody or antibody fragment of any one of paragraphs 1 to 7, wherein antibody or antibody fragment is for administration to a human that is receiving or has received statin treatment or has reduced responsiveness to statin treatment.","9.The antibody or antibody fragment of paragraph 7 or 8, wherein said antibody or antibody fragment is for administration to the human separately or simultaneously with said statin treatment.","10.The antibody or antibody fragment of any one of paragraphs 4 to 8, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine and/or saliva of said human.","11.The antibody or antibody fragment of any one of paragraphs 1 to 10, wherein said human is indicated as heterozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising a mutation I474V or E670G, optionally, wherein said human is further indicated as comprising the nucleotide sequence of SEQ ID NO: 28, or said human is indicated as homozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising a mutation I1474V or E670G in SEQ ID NO: 1.12.The antibody or antibody fragment of any one of paragraphs 1 to 11, wherein said human has been diagnosed with at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.","13.The antibody or antibody fragment of any one of paragraphs 1 to 12, wherein said antibody or antibody fragment treats or reduces the risk in said human of at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.","14.The antibody or antibody fragment of any one of paragraphs 1 to 13, wherein the nucleotide sequence is SEQ ID NO: 29 or 30.15.The antibody or antibody fragment of any one of paragraphs 1 to 14, wherein said antibody or antibody fragment is for administration by intravenous or subcutaneous administration and/or is comprised in an injectable preparation.","Further exemplary methods are in the paragraphs 1-16 as follows.","1.A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 or E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human IGLC2*01 lambda light chain constant region and wherein said human comprises (i) an IGLC2*01 human light chain constant region gene segment, or the human expresses antibodies comprising a human IGLC2*01 lambda light chain constant regions and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.In an embodiment, said mutation is I474V.","In another embodiment, said mutation is E670G.","An example provides:— A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 in SEQ ID NO: 1, wherein the antibody or fragment comprises a human IGLC2*01 lambda light chain constant region and wherein said human comprises (i) an IGLC2*01 human light chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V in SEQ ID NO: 1.Optionally, the antibody or fragment comprises an IGLC2*01 human light chain constant region.","Another example provides:— A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human IGLC2*01 lambda light chain constant region and wherein said human comprises (i) an IGLC2*01 human light chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation E670G in SEQ ID NO: 1.Optionally, the antibody or fragment comprises an IGLC2*01 human light chain constant region.","In an example, said antibody or antibody fragment has been determined to specifically bind a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 or E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human IGLC2*01 lambda light chain constant region and wherein said human comprises (i) an IGLC2*01 human heavy chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1 2.The method of paragraph 1, comprising, before said administering, selecting said human comprising said nucleotide sequence of (ii).","3.The method of paragraph 1 or 2, wherein the human has been determined to comprise the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1 and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein encoded by the nucleotide sequence of SEQ ID NO: 29 or 30.4.The method of any one of paragraphs 1 to 3, comprising the step of determining that the human comprises the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein comprising said mutation I474V or E670G, optionally, wherein the determining step is performed before administration of the antibody to the human.","5.The method of paragraph 4, wherein the step of determining comprises assaying a biological sample from the human for a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.6.The method of paragraph 5, wherein the assaying comprises contacting the biological sample with a. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides that can specifically hybridize to and identify in the biological sample a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or that specifically hybridizes to an antisense of said sequence, wherein said nucleic acid hybridizes to at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 or hybridizes to an antisense sequence thereby forming a complex when at least one nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and/or b. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides of a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or comprising an antisense sequence of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 thereby forming a complex when the nucleotide sequence encoding the PCSK9 that comprises a C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and detecting the presence or absence of the complex, wherein detecting the presence of the complex determines that the human comprises the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.7.The method of paragraph 5 or 6, wherein the assaying comprises nucleic acid amplification and optionally one or more methods selected from sequencing, next generation sequencing, nucleic acid hybridization, and allele-specific amplification and/or wherein the assaying is performed in a multiplex format.","8.The method of any one of paragraphs 1 to 7, wherein said human is or has been further determined to be substantially resistant to statin treatment.","9.The method of any one of paragraphs 1 to 8, wherein said human is receiving or has received statin treatment or has reduced responsiveness to statin treatment.","10.The method of paragraph 8 or 9, wherein said antibody or antibody fragment is administered to the human separately or simultaneously with said statin treatment.","11.The method of any one of paragraphs 5 to 7, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine and/or saliva of said human.","12.The method of any one of paragraphs 1 to 11, wherein said human is indicated as heterozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising said mutation I474V or E670G, optionally, wherein said human is further indicated as comprising the nucleotide sequence of SEQ ID NO: 28, or said human is indicated as homozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.13.The method of any one of paragraphs 1 to 12, wherein said human has been diagnosed with at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.","14.The method of any one of paragraphs 1 to 13, wherein said antibody or antibody fragment treats or reduces the risk in said human of at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.","15.The method of any one of paragraphs 1 to 14, wherein the nucleotide sequence is SEQ ID NO: 29 or 30.16.The method of any one of paragraphs 1 to 15, wherein said antibody or antibody fragment is administered by intravenous or subcutaneous administration and/or is comprised in an injectable preparation.","Further exemplary ligands are in the paragraphs 1-15 as follows.","1.An antibody or antibody fragment for use in a method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, wherein the antibody or fragment comprises a human variable domain that is derived from the recombination of a human VH gene segment, a human D gene segment and a human JH gene segment, wherein the VH gene segment is as defined in any one of clauses 80 to 90, and the antibody or fragment specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) amino acid sequence that comprises a C-terminal domain comprising a mutation I474V or E670G in SEQ ID NO: 1, wherein the human comprises a nucleotide sequence encoding said amino acid sequence, and comprises said VH gene segment or expresses antibodies comprising VH domains that are derived from the recombination of said human VH gene segment, a human D gene segment and a human JH gene segment.","In an embodiment, said mutation is I474V.","In another embodiment, said mutation is E670G.","2.The antibody or antibody fragment of paragraph 1, wherein the human has been determined to comprise the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1 and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein encoded by the nucleotide sequence of SEQ ID NO: 29 or 30.3.The antibody or antibody fragment of paragraphs 1 or 2, the method comprising the step of determining that the human comprises the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein comprising said mutation I474V or E670G, optionally, wherein the determining step is performed before administration of the antibody to the human.","4.The antibody or antibody fragment of paragraph 3, wherein the step of determining comprises assaying a biological sample from the human for a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.5.The antibody or antibody fragment of paragraph 4, wherein the assaying comprises contacting the biological sample with a. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides that can specifically hybridize to and identify in the biological sample a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or that specifically hybridizes to an antisense of said sequence, wherein said nucleic acid hybridizes to at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 or hybridizes to an antisense sequence thereby forming a complex when at least one nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and/or b. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides of a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or comprising an antisense sequence of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 thereby forming a complex when the nucleotide sequence encoding the PCSK9 that comprises a C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and detecting the presence or absence of the complex, wherein detecting the presence of the complex determines that the human comprises the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.6.The antibody or antibody fragment of paragraph 4 or 5, wherein the assaying comprises nucleic acid amplification and optionally one or more methods selected from sequencing, next generation sequencing, nucleic acid hybridization, and allele-specific amplification and/or wherein the assaying is performed in a multiplex format.","7.The antibody or antibody fragment of any one of paragraphs 1 to 6, wherein said antibody or antibody fragment is for administration to a human that is or has been further determined to be substantially resistant to statin treatment.","8.The antibody or antibody fragment of any one of paragraphs 1 to 7, wherein antibody or antibody fragment is for administration to a human that is receiving or has received statin treatment or has reduced responsiveness to statin treatment.","9.The antibody or antibody fragment of paragraph 7 or 8, wherein said antibody or antibody fragment is for administration to the human separately or simultaneously with said statin treatment.","10.The antibody or antibody fragment of any one of paragraphs 4 to 8, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine and/or saliva of said human.","11.The antibody or antibody fragment of any one of paragraphs 1 to 10, wherein said human is indicated as heterozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising a mutation I474V or E670G, optionally, wherein said human is further indicated as comprising the nucleotide sequence of SEQ ID NO: 28, or said human is indicated as homozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising a mutation I474V or E670G in SEQ ID NO: 1.12.The antibody or antibody fragment of any one of paragraphs 1 to 11, wherein said human has been diagnosed with at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.","13.The antibody or antibody fragment of any one of paragraphs 1 to 12, wherein said antibody or antibody fragment treats or reduces the risk in said human of at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.","14.The antibody or antibody fragment of any one of paragraphs 1 to 13, wherein the nucleotide sequence is SEQ ID NO: 29 or 30.15.The antibody or antibody fragment of any one of paragraphs 1 to 14, wherein said antibody or antibody fragment is for administration by intravenous or subcutaneous administration and/or is comprised in an injectable preparation.","Further exemplary methods are in the paragraphs 1-16 as follows.","1.A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 or E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human variable domain that is derived from the recombination of a human VH gene segment, a human D gene segment and a human JH gene segment, wherein the VH gene segment is as defined in any one of clauses 80 to 90 and wherein said human comprises (i) comprises said VH gene segment or expresses antibodies comprising VH domains that are derived from the recombination of said human VH gene segment, a human D gene segment and a human JH gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.In an embodiment, said mutation is I474V.","In another embodiment, said mutation is E670G.","2.The method of paragraph 1, comprising, before said administering, selecting said human comprising said nucleotide sequence of (ii).","3.The method of paragraph 1 or 2, wherein the human has been determined to comprise the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1 and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein encoded by the nucleotide sequence of SEQ ID NO: 29 or 30.4.The method of any one of paragraphs 1 to 3, comprising the step of determining that the human comprises the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein comprising said mutation I474V or E670G, optionally, wherein the determining step is performed before administration of the antibody to the human.","5.The method of paragraph 4, wherein the step of determining comprises assaying a biological sample from the human for a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.6.The method of paragraph 5, wherein the assaying comprises contacting the biological sample with a. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides that can specifically hybridize to and identify in the biological sample a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or that specifically hybridizes to an antisense of said sequence, wherein said nucleic acid hybridizes to at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 or hybridizes to an antisense sequence thereby forming a complex when at least one nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and/or b. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides of a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or comprising an antisense sequence of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 thereby forming a complex when the nucleotide sequence encoding the PCSK9 that comprises a C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and detecting the presence or absence of the complex, wherein detecting the presence of the complex determines that the human comprises the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.7.The method of paragraph 5 or 6, wherein the assaying comprises nucleic acid amplification and optionally one or more methods selected from sequencing, next generation sequencing, nucleic acid hybridization, and allele-specific amplification and/or wherein the assaying is performed in a multiplex format.","8.The method of any one of paragraphs 1 to 7, wherein said human is or has been further determined to be substantially resistant to statin treatment.","9.The method of any one of paragraphs 1 to 8, wherein said human is receiving or has received statin treatment or has reduced responsiveness to statin treatment.","10.The method of paragraph 8 or 9, wherein said antibody or antibody fragment is administered to the human separately or simultaneously with said statin treatment.","11.The method of any one of paragraphs 5 to 7, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine and/or saliva of said human.","12.The method of any one of paragraphs 1 to 11, wherein said human is indicated as heterozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising said mutation I474V or E670G, optionally, wherein said human is further indicated as comprising the nucleotide sequence of SEQ ID NO: 28, or said human is indicated as homozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.13.The method of any one of paragraphs 1 to 12, wherein said human has been diagnosed with at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.","14.The method of any one of paragraphs 1 to 13, wherein said antibody or antibody fragment treats or reduces the risk in said human of at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.","15.The method of any one of paragraphs 1 to 14, wherein the nucleotide sequence is SEQ ID NO: 29 or 30.16.The method of any one of paragraphs 1 to 15, wherein said antibody or antibody fragment is administered by intravenous or subcutaneous administration and/or is comprised in an injectable preparation.","Regimens A: The invention further provides the following regimens, ligands and kits.","1.A method for treating a human PCSK9-mediated disease or condition in a human by targeting a rare variant human PCSK9, the method comprising administering to the human a ligand (eg, an antibody or fragment) that has been determined to specifically bind to said PCSK9 variant; wherein the human expresses said PCSK9 variant or the genome of the human comprises a nucleotide sequence encoding said PCSK9 variant; wherein said human is treated for said disease or condition.","The variant PCSK9 can, for example, be any rare variant as described herein.","For example, there is provided: 1a.","A method for treating a PCSK9-mediated disease or condition in a human by targeting a PCSK9 that comprises a C-terminal domain amino acid polymorphism (compared to SEQ ID NO: 1), the method comprising administering to the human a ligand (eg, an antibody or fragment) that has been determined to specifically bind to a PCSK9 comprising a C-terminal domain comprising I474V or 670G (numbering according to SEQ ID NO: 1); wherein the human expresses said PCSK9 or the genome of the human comprises a nucleotide sequence encoding said PCSK9; wherein said human is treated for said disease or condition.","In an embodiment, determination of said specific binding is by reference to binding assay data, eg, as determined using SPR or ELISA.","Determination may, for example, be by reference to information in a printed publication, eg, with knowledge of data presented in the present or another patent application or in a journal article.","Once armed with such knowledge (eg, in the absence of further testing of binding), the skilled person is able—by direction of the present invention—to treat a relevant human whose genotype or phenotype matches the binding specificity of the ligand.","The antibody or fragment can be according to any configuration, example, embodiment, aspect, clause or paragraph herein.","In an embodiment, the method comprises, before said administering, selecting a human comprising said nucleotide sequence encoding the PCSK9, wherein the human is said human in clause 1 (eg, 1a).","2.The method of clause 1, comprising before said administering the step of determining that the ligand specifically binds to said PCSK9, eg, using SPR or ELISA.","3.The method of clause 1 or 2, wherein the specific binding to said PCSK9 is binding with a dissociation constant (Kd) of 1 nM or less, eg, 100, 10 or 1 pM or less.","4.The method of any of clauses 1 to 3 (eg, clause 1a), wherein the condition is elevated LDL-cholesterol or is caused by elevated LDL-cholesterol.","5.The method of clause 4 (eg, when dependent from clause 1a), wherein the condition is selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.","6.The method of any one of clauses 1 to 5 (eg, when dependent from clause 1a), wherein the human has been determined to comprise the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1 and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein encoded by the nucleotide sequence of SEQ ID NO: 29 or 30.7.The method of any one of clauses 1 to 6 (eg, when dependent from clause 1a), comprising the step of determining that the human comprises the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein comprising said mutation I474V or E670G, optionally, wherein the determining step is performed before administration of the antibody to the human.","8.The method of clause 7, wherein the step of determining comprises assaying a biological sample from the human for a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.9.The method of clause 8, wherein the assaying comprises contacting the biological sample with a. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides that can specifically hybridize to and identify in the biological sample a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or that specifically hybridizes to an antisense of said sequence, wherein said nucleic acid hybridizes to at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 or hybridizes to an antisense sequence thereby forming a complex when at least one nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and/or b. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides of a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or comprising an antisense sequence of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 thereby forming a complex when the nucleotide sequence encoding the PCSK9 that comprises a C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and detecting the presence or absence of the complex, wherein detecting the presence of the complex determines that the human comprises the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.10.The method of clause 8 or 9, wherein the assaying comprises nucleic acid amplification and optionally one or more methods selected from sequencing, next generation sequencing, nucleic acid hybridization, and allele-specific amplification and/or wherein the assaying is performed in a multiplex format.","11.The method of any one of clauses 1 to 10, wherein said human is or has been further determined to be substantially resistant to statin treatment.","12.The method of any one of clauses 1 to 11, wherein said human is receiving or has received statin treatment or has reduced responsiveness to statin treatment.","13.The method of clauses 11 or 12, wherein said antibody or antibody fragment is administered to the human separately or simultaneously with said statin treatment.","14.The method of any one of clauses 8 to 10, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine and/or saliva of said human.","15.The method of any one of clauses 1 to 14, wherein said human is indicated as heterozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising said mutation I474V or E670G, optionally, wherein said human is further indicated as comprising the nucleotide sequence of SEQ ID NO: 28, or said human is indicated as homozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.16.The method of any one of clauses 1 to 15, wherein said human has been diagnosed with at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.","17.The method of any one of clauses 1 to 16, wherein said antibody or antibody fragment treats or reduces the risk in said human of at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.","18.The method of any one of clauses 1 to 17, wherein the nucleotide sequence is SEQ ID NO: 29 or 30.19.The method of any one of clauses 1 to 18, wherein said antibody or antibody fragment is administered by intravenous or subcutaneous administration and/or is comprised in an injectable preparation.","20.A ligand (eg, an antibody or fragment) for use in the method of any one of clauses 1 to 19, wherein the ligand specifically binds the PCSK9.21.A kit comprising the ligand of clause 20 and instructions for carrying out the method of any one of clauses 1 to 19.B: The invention further provides the following regimens, ligands and kits.","1.A method of reducing cholesterol level or maintaining a previously reduced cholesterol level in a human in need thereof, the method comprising:— a.","Carrying out an initial treatment of said human for an initial treatment period by administering an anti-human PCSK9 ligand (eg, an antibody or fragment) to said human, wherein (i) the ligand has been determined to specifically bind to a PCSK9 comprising a C-terminal domain comprising I474V or 670G (numbering according to SEQ ID NO: 1); (ii) the human expresses said PCSK9 or the genome of the human comprises a nucleotide sequence encoding said PCSK9 and (iii) the human has received or is receiving statin treatment to lower or maintain cholesterol level; wherein the initial treatment comprises the administration of a single or multiple doses of the ligand to the human; b.","Determining to (i) terminate statin treatment (ii) keep the human off statin treatment; or (iii) reduce statin treatment after said initial treatment period; and c. Continuing to administer the ligand to said patient after said time period has expired, thereby reducing cholesterol level or maintaining a previously reduced cholesterol level in said human.","In an embodiment, determination of said specific binding is by reference to binding assay data, eg, as determined using SPR or ELISA.","Determination may, for example, be by reference to information in a printed publication, eg, with knowledge of data presented in the present or another patent application or in a journal article.","Once armed with such knowledge (eg, in the absence of further testing of binding), the skilled person is able—by direction of the present invention—to treat a relevant human whose genotype or phenotype matches the binding specificity of the ligand.","The antibody or fragment can be according to any configuration, example, embodiment, aspect, clause or paragraph herein.","A pharmaceutically-effective amount of said ligand is administered.","In an embodiment, the method comprises, before said administering, selecting a human comprising said nucleotide sequence encoding the PCSK9, wherein the human is said human recited in clause 1.In an example, the initial treatment period is 7 days, 14 days, 21 days, 28 days, a month, two months, three months, four months, five months, six months, seven months, eight months, nine months or a year.","2.The method of clause 1, wherein the human has or is suffering from statin-associated memory loss or a statin-associated neurodegenerative condition, or has or is at increased risk of diabetes (eg, statin-associated diabetes).","3.The method of clause 1 or 2, comprising, before said initial treatment, the step of determining that the human has or is suffering from statin-associated memory loss or a statin-associated neurodegenerative condition, or has or is at increased risk of diabetes (eg, statin-associated diabetes).","4.The method of clause 2 or 3, comprising, after step (b) (eg, during step (c)) determining that the memory loss or said neurodegenerative condition has improved.","5.The method of any one of clauses 1 to 4, wherein said human is over 40 years of age (eg, 50 or over, 55 or over, 60 or over, 65 or over, or 70 or over).","6.The method of any one of clauses 1 to 5, wherein step (c) comprises determining to increase the doses of said ligand to be administered after said initial treatment period and administering said increased doses to said human.","7.The method of any one of clauses 1 to 6, wherein step (b) comprises determining that the human is intolerant or refactory to treatment by a statin.","8.The method of any one of clauses 1 to 7, wherein the initial treatment comprises the administration of a statin, fenofibrate (eg, Tricor™ or Lofibra™) or ezetimibe to the human in addition to the ligand.","9.The method of any one of clauses 1 to 8, wherein step (b) comprises terminating or reducing statin, fenofibrate (eg, Tricor™ or Lofibra™) or ezetimibe treatment during step (c).","10.The method of any one of clauses 1 to 9, comprising increasing (ie, increasing compared to the initial treatment dose) the ligand dose during step (c).","11.The method of any one of clauses 1 to 10, wherein the human has received high dose statin treatment prior to the initial treatment, and wherein step (c) comprises administering a lower (eg, a medium or low) dose statin treatment in addition to said ligand.","The skilled person is familiar with the meaning of high, medium and low dose treatments (and how to determine according to each patient, eg, the patient's body mass).","For example, the statin is selected from rosuvastatin, atorvastatin and simvastatin.","For example daily statin doses are as follows:—Low 10 to 20 mg (eg, 10 mg); medium>20 and <60 mg (eg, 40 mg); high 60-100 mg (eg, 80 mg).","12.The method of any one of clauses 1 to 10, wherein the human has received medium dose statin treatment prior to the initial treatment, and wherein step (c) comprises administering a lower (eg, a low) dose statin treatment or no statin in addition to said ligand.","13.The method of any one of clauses 1 to 10, wherein the human has received low dose statin treatment prior to the initial treatment, and wherein step (c) comprises administering no statin in addition to said ligand.","14.The method of any one of clauses 1 to 13, comprising, before the initial treatment, the step of determining that the ligand specifically binds to said PCSK9, eg, using SPR or ELISA.","15.The method of any one of clauses 1 to 14, wherein the specific binding to said PCSK9 is binding with a dissociation constant (Kd) of 1 nM or less, eg, 100, 10 or 1 pM or less.","16.The method of any of clauses 1 to 15, wherein the human is at risk of or suffering from a condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.","17.The method of clause 16, wherein step (c) treats or reduces the risk of said condition in the human.","18.The method of any one of clauses 1 to 17, wherein the human has been determined to comprise the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1 and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein encoded by the nucleotide sequence of SEQ ID NO: 29 or 30.19.The method of any one of clauses 1 to 18, comprising the step of determining that the human comprises the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein comprising said mutation I474V or E670G, optionally, wherein the determining step is performed before administration of the antibody to the human.","20.The method of clause 19, wherein the step of determining comprises assaying a biological sample from the human for a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.21.The method of clause 20, wherein the assaying comprises contacting the biological sample with a. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides that can specifically hybridize to and identify in the biological sample a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or that specifically hybridizes to an antisense of said sequence, wherein said nucleic acid hybridizes to at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 or hybridizes to an antisense sequence thereby forming a complex when at least one nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and/or b. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides of a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or comprising an antisense sequence of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 thereby forming a complex when the nucleotide sequence encoding the PCSK9 that comprises a C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and detecting the presence or absence of the complex, wherein detecting the presence of the complex determines that the human comprises the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.22.The method of clause 20 or 21, wherein the assaying comprises nucleic acid amplification and optionally one or more methods selected from sequencing, next generation sequencing, nucleic acid hybridization, and allele-specific amplification and/or wherein the assaying is performed in a multiplex format.","23.The method of any one of clauses 1 to 22, wherein said human is or has been further determined to be substantially resistant to statin treatment.","24.The method of any one of clauses 20 to 22, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine and/or saliva of said human.","25.The method of any one of clauses 1 to 24, wherein said human is indicated as heterozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising said mutation I474V or E670G, optionally, wherein said human is further indicated as comprising the nucleotide sequence of SEQ ID NO: 28, or said human is indicated as homozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.26.The method of any one of clauses 1 to 25, wherein said human has been diagnosed with at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.","27.The method of any one of clauses 1 to 26, wherein the nucleotide sequence is SEQ ID NO: 29 or 30.28.The method of any one of clauses 1 to 27, wherein said ligand (eg, antibody or antibody fragment) is administered by intravenous or subcutaneous administration and/or is comprised in an injectable preparation.","29.A ligand (eg, an antibody or fragment) for use in the method of any one of clauses 1 to 28, wherein the ligand specifically binds the PCSK9.30.A kit comprising the ligand of clause 29 and instructions for carrying out the method of any one of clauses 1 to 28.In an example of any aspect of the invention, the ligand (eg, antibody or fragment, eg, alirocumab, bocovizumab or evolocumab, or an antibody or fragment comprising the variable domains of 316P or 31H4) is administered to the human at a two-weekly dose of from 75 to 150 mg (eg, from 75 to 150 mg administered once or twice over a two-week period).","In an example, the ligand is for such administration to the human.","Determination of Specific Binding of Ligands of the Invention to PCSK9 Variants Method of SPR Determination of Binding Binding of the antibodies to the PCSK9 variants was carried out by SPR using the ProteOn XPR36™ Array system (BioRad).","An anti-human IgG surface (Jackson Labs 109-005-008) was created on a GLC Biosensor chip by primary amine coupling.","Test antibodies were captured on this surface as ligands.","The PCSK9 variants were used as analytes and passed over the captured antibodies at 256 nM, 64 nM, 16 nM, 4 nM and 1 nM.","Binding curves were double referenced using a buffer injection (i.e.","0 nM) to remove baseline drift and injection artefacts.","Regeneration of the capture surface was with 100 mM phosphoric acid which removed the captured antibody allowing another cycle of capture and binding.","The binding sensorgrams generated were analysed using the 1:1 model inherent to the ProteOn XPR36 Array system analysis software.","The assay was performed at 25° C. and using 1×HBS-EP (Teknova) as running buffer.","Data Three antibodies were tested and the resulting binding data are presented below (Table 3).","Antibodies 316P and 31H4 are antibodies disclosed in US20110065902A1 (the sequences of these antibodies and their variable domains are incorporated herein by reference for possible use in the present invention and possible inclusion in claims herein).","Antibody 316P comprises heavy chain variable domains derived from recombination of human VH3-23*04 and JH2*01 (with a D), and light chain variable domains derived from recombination of human Vκ4-1*01 and Jκ2*01.Evolocumab comprises a human IGHG2*01 heavy chain and a human IGLC2*01 lambda light chain, a VH derived from recombination of human IGHV1-18*01 and IGHJ6*01 (with a D segment) and a Vλ derived from recombination of human IGLV2-14*01 and IGLJ2*01.TABLE 3 SPR Determination of Ligand Binding Specificity for PCSK9 Variants Variant/Antibody ka (1/Ms) kd (1/s) KD (nM) PCSK9 a 316P 1.37E+06 2.75E−04 0.201 31H4 1.14E+06 6.38E−05 0.056 Evolocumab 1.14E+05 2.62E−05 0.229 PCSK9 a′ 316P 1.50E+06 2.72E−04 0.181 31H4 1.23E+06 6.06E−05 0.049 Evolocumab 1.24E+05 2.29E−05 0.185 PCSK9 c 316P 1.49E+06 2.75E−04 0.184 31H4 1.22E+06 5.69E−05 0.047 Evolocumab 1.20E+05 2.20E−05 0.183 PCSK9 r 316P 1.40E+06 2.76E−04 0.197 31H4 1.15E+06 5.82E−05 0.051 Evolocumab 1.16E+05 2.67E−05 0.230 PCSK9 f 316P 1.39E+06 2.82E−04 0.203 31H4 1.13E+06 5.95E−05 0.053 Evolocumab 1.16E+05 2.66E−05 0.229 PCSK9 p 316P 1.39E+06 2.73E−04 0.196 31H4 1.14E+06 6.12E−05 0.054 Evolocumab 1.14E+05 2.50E−05 0.219 Results The results showed that all antibodies tested bound to PCSK9 variants equally, with any binding variation seen being within experimental error for such a strong affinity interaction.","Thus, the invention determines that an antibody with the following profile can specifically bind one or more variants of the invention:— 1.An antibody (eg, 316P or alirocumab) that comprises heavy chain variable domains derived from recombination of human IGHV3-23*04 and IGHJH2*01 (with a D), and light chain variable domains derived from recombination of human IGKV4-1*01 and IGKJ2*01; or 2.An antibody (eg, evolocumab) that comprises human heavy chain variable domains derived from recombination of human IGHV1-18*01 and IGHJ6*01 (with a D segment) and light chain variable domains derived from recombination of human IGLV2-14*01 and IGLJ2*01.Thus, according to the invention, the skilled person is hereby provided with the required determination of specific binding of the ligand to PCSK9 variants.","Applications of this determination are set out above in the context of methods and other aspects of the invention.","REFERENCES Horton et al, Trends Biochem Sci.","2007 February; 32(2):71-7.Epub 2007 Jan. 9, Molecular biology of PCSK9: its role in LDL metabolism.","Seidah and Prat, J Mol Med (Berl).","2007 July; 85(7):685-96.Epub 2007 Mar.","10, The proprotein convertases are potential targets in the treatment of dyslipidemia.","Benjannet et al, J Biol Chem.","2004 Nov. 19; 279(47):48865-75.Epub 2004 Sep. 9, NARC-1/PCSK9 and its natural mutants: zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol.","Lagace et al, J Clin Invest.","2006 November; 116(11):2995-3005, Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice.","Maxwell et al, Proc Natl Acad Sci USA.","2005 Feb. 8; 102(6):2069-74.Epub 2005 Jan. 27, Overexpression of PCSK9 accelerates the degradation of the LDLR in a post-endoplasmic reticulum compartment.","Park et al, J Biol Chem.","2004 Nov. 26; 279(48):50630-8.Epub 2004 Sep. 22, Post-transcriptional regulation of low density lipoprotein receptor protein by proprotein convertase subtilisin/kexin type 9a in mouse liver.","Rashid et al, Proc Natl Acad Sci USA.","2005 Apr.","12; 102(15):5374-9.Epub 2005 Apr.","1, Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9.Kotowski et al, Am J Hum Genet.","2006 March; 78(3):410-22.Epub 2006 Jan. 20, A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol.","Chen et al, J Am Coll Cardiol.","2005 May 17; 45(10): 1611-9.Epub 2005 Apr.","21, A common PCSK9 haplotype, encompassing the E670G coding single nucleotide polymorphism, is a novel genetic marker for plasma low-density lipoprotein cholesterol levels and severity of coronary atherosclerosis.","Pisciotta et al, Atherosclerosis.","2006 June; 186(2):433-40.Epub 2005 Sep. 23, Additive effect of mutations in LDLR and PCSK9 genes on the phenotype of familial hypercholesterolemia.","Zhao et al, Am J Hum Genet.","2006 September; 79(3):514-23.Epub 2006 Jul.","18, Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote.","Seidah et al, Proc Natl Acad Sci USA.","2003 Feb. 4; 100(3):928-33.Epub 2003 Jan. 27, The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation.","TABLE 4 1000 GENOMES PROJECT HUMAN POPULATIONS Below is a summary of the ethnic populations as per the 1000 Genomes Project sequences.","Population European ancestry Utah residents (CEPH) with Northern and Western European ancestry (CEU) Toscani in Italia (TSI) British from England and Scotland (GBR) Finnish from Finland (FIN) Iberian populations in Spain (IBS) East Asian ancestry Han Chinese in Beijing, China (CHB) Japanese in Toyko, Japan (JPT) Han Chinese South (CHS) Chinese Dai in Xishuangbanna (CDX) Kinh in Ho Chi Minh City, Vietnam (KHV) Chinese in Denver, Colorado (CHD) (pilot 3 only) West African ancestry Yoruba in Ibadan, Nigeria (YRI) Luhya in Webuye, Kenya (LWK) Gambian in Western Division, The Gambia (GWD) Malawian in Blantyre, Malawi (MAB) West African Population (TBD) Americas African Ancestry in Southwest US (ASW) African American in Jackson, MS (AJM) African Caribbean in Barbados (ACB) Mexican Ancestry in Los Angeles, CA (MXL) Puerto Rican in Puerto Rico (PUR) Colombian in Medellin, Colombia (CLM) Peruvian in Lima, Peru (PEL) South Asian ancestry Ahom in the State of Assam, India Kayadtha in Calcutta, India Reddy in Hyderabad, India Maratha in Bombay, India Punjabi in Lahore, Pakistan TABLE 5 TOIs & Related Diseases, Conditions and Example Ligands Example Disease or Human TOI Condition Example Ligand Il-17a Inflammatory Disease AIN457 Uveitis Ixekizumab Rheumatoid Arthritis Psoriasis Angiotensin II Receptor Type 1 (AT1) Hypertension LCZ696 Neprilysin Hypertension LCZ696 Metabotropic Glutamate Receptor 5 (Mglur5) Fragile X Syndrome AFQ056 Mavoglurant A Histone Deacetylase Cancer, Eg, Multiple LBH589 Myeloma Panobinostat Diacylglycerol acyltransferase-1 (DGAT-1) Familial LCQ908 Chylomicronaemia Pradigastat Syndrome Smoothened (Smo) Basal cell carcinoma LDE225 Solid tumour Myelofibrosis Medulloblastoma Solid tumour Smoothened (Smo) receptor Basal cell carcinoma LEQ506 Solid tumors ALK Non small cell lung LDK378 carcinoma (NSCLC) phosphatidylinositol-3-kinase (PI3K) Cancer, eg, solid tumour, BKM120 mTOR breast cancer, Renal cell AKT carcinoma (RCC), Endometrial cancer, Non- small cell lung cancer (NSCLC), prostate cancer, Glioblastoma multiforme (GBM) CRPC GIST Myelofibrosis mTOR Cancer, eg, solid tumour, BEZ235 PI3K breast cancer, Renal cell AKT carcinoma (RCC), Endometrial cancer, Non- small cell lung cancer (NSCLC), prostate cancer, Glioblastoma multiforme (GBM) CRPC GIST Myelofibrosis PI3Kα Cancer, eg, solid tumour, BYL719 mTOR breast cancer, Renal cell PI3K carcinoma (RCC), AKT Endometrial cancer, Non- small cell lung cancer (NSCLC), prostate cancer, Glioblastoma multiforme (GBM) CRPC GIST Myelofibrosis Mitogen-activated ERK kinase 1 (MEK1) Cancer, eg, solid tumour, MEK162 Mitogen-activated ERK kinase 2 (MEK2) melanoma, pancreatic, colon, lung or thyroid cancer Metastasis protein kinase Acute myeloid leukemia PKC412 protein kinase C (AML) Midostaurin FLT-3 Myelodysplastic syndrome c-KIT (MDS) Aggressive systemic mastocytosis (ASM) ActRIIB Sporadic inclusion body BYM338 myositis (sIBM) bimagrumab CD19 Cancer, eg, CTL019 (formerly CART- Leukaemia, mast 19) cell leukemia, Acute Lymphoblastic Leukemia, Chronic lymphocytic leukemia (CLL) or Hematological tumors 11β-hydroxylase Cushing's syndrome LCI699 BRAF Cancer, eg, melanoma LGX818 Receptor Tyrosine Kinase Cancer, eg, solid TKI258 (formerly CHIR- FGFR tumour 258) Breast Cancer Dovitinib Endometrial cancer Hepatocellular carcinoma Renal cell carcinoma (RCC) Bladder cancer multiple myeloma (MM), hepatocellular carcinoma endometrial cancer DAC enzyme hematologic malignancy LBH589 Multiple myeloma panobinostat Myel\\odysplastic syndrome (MDS) Myelofibrosis HSP90 Cancer, eg, Breast AUY922 Cancer, gastric cancer or Non- small cell lung cancer (NSCLC) FGFR Cancer, eg, solid BGJ398 tumour Breast Cancer Endometrial cancer Hepatocellular carcinoma Renal cell carcinoma (RCC) Bladder cancer multiple myeloma (MM), hepatocellular carcinoma endometrial cancer cIAP1 Cancer, eg, solid LCL161 cIAP2 tumour Breast Cancer Endometrial cancer Hepatocellular carcinoma Renal cell carcinoma (RCC) Bladder cancer multiple myeloma (MM), hepatocellular carcinoma endometrial cancer Akt Cancer, eg, Solid GDC-0068 tumour, gastric RG7440 cancer (eg, castration-resistant prostate cancer), prostate cancer, gastroesophageal junction cancer CD22 Hematologic malignancies DCDT2980S Non-Hodgkin's lymphoma RG7593 (eg, relapsed or refractory follicular non-Hodgkin's lymphoma) Diffuse large B-cell lymphoma (eg, relapsed or refractory diffuse large B- cell lymphoma) CD79b Hematologic malignancies DCDS4501A Non-Hodgkin's lymphoma RG7596 (eg, relapsed or refractory follicular non-Hodgkin's lymphoma) Diffuse large B-cell lymphoma (eg, relapsed or refractory diffuse large B- cell lymphoma) endothelin B receptor (ETBR) Melanoma, eg, metastatic DEDN6526A or unresectable melanoma RG7636 HER3 Cancer, eg, metastatic MEHD7945A epithelial tumour, RG7597 metastatic squamous cell carcinoma of the head and neck cancer, metastatic colorectal cancer EGFR Cancer, eg, metastatic MEHD7945A epithelial tumour, RG7597 metastatic squamous cell Necitumumab carcinoma of the head and neck cancer, metastatic colorectal cancer MUC16 Cancer, eg, ovarian cancer DMUC5754A (eg, platinum-resistant RG7458 ovarian cancer) sodium-dependent phosphate transport protein Cancer, eg, metastatic non- DNIB0600A 2b (NaPi2b) squamous non-small cell RG7599 lung cancer, ovarian cancer (eg, platinum-resistant ovarian cancer) PDL1 (programmed death ligand 1) Cancer, eg, solid tumour MPDL3280A metastatic melanoma RG7446 non-small cell lung cancer STEAP1 (six-transmembrane epithelial Cancer, eg, prostate cancer DSTP3086S antigen of the prostate 1) (eg, metastatic castration- RG7450 resistant prostate cancer) Bcl-2 Cancer, eg, leukaemia (eg, GDC-0199 chronic lymphocytic RG7601 leukaemia), non-Hodgkin's lymphoma Checkpoint kinase 1 (ChK1) Cancer, eg, solid tumour, GDC-0425 refractory solid tumour or RG7602 lymphoma GDC-0575 RG7741 mitogen activated protein kinase kinase Cancer, eg, solid tumour, GDC-0973 (MAPKK) melanoma (eg, metastatic RG7421 MEK melanoma) Cobimetinib GDC-0623 RG7420 epidermal growth factor domain-like-7 Cancer, eg, colorectal Parsatuzumab (EGFL7) cancer (eg, metastatic MEGF0444A colorectal cancer), NSCLC RG7414 phosphatidylinositol-3-kinase (PI3K) Cancer, eg, prostate cancer, GDC-0032 renal cell carcinoma, RG7604 endometrial cancer, breast GDC-0084 cancer (eg, HER2-negative RG7666 metastatic breast cancer, Pictilisib metastatic hormone GDC-0941 receptor-positive breast RG7321 cancer), solid tumour mTOR Cancer, eg, prostate cancer, GDC-0980 TORC1 renal cell carcinoma, RG7422 TORC2 endometrial cancer, breast PI3K cancer (eg, HER2-negative metastatic breast cancer, metastatic hormone receptor-positive breast cancer), solid tumour IL17 Autoimmune disease Secukinumab Ankylosing spondylitis; ixekizumab Asthma; Multiple myeloma; Multiple sclerosis; Polymyalgia rheumatica; Psoriasis; Psoriatic arthritis; Rheumatoid arthritis; Uveitis M1 prime segment of membrane IgE Allergic Asthma Quilizumab MEMP1972A RG7449 IFN alpha Autoimmune disease Rontalizumab Systemic lupus erythematosus PCSK9 (proprotein convertase subtilisin/kexin coronary heart disease MPSK3169A type 9) (CHD) or high risk of CHD RG7652 hyperlipidaemia hypercholesterolaemia stroke atherosclerosis a cardiovascular disease or condition a condition associated with elevated LDL Vascular Endothelial Growth Factor-A Diabetic Macular Edema EYLEA ® (VEGF-A) (DME), Aflibercept Placental Growth Factor (PlGF) Branch Retinal Vein AVASTIN ™ Occlusion (BRVO) LUCENTIS ™ Wet age-related macular degeneration (Wet AMD) IL-6 receptor Inflammatory disease, eg, Sarilumab rheumatoid arthritis REGN88 Uveitis (eg, non-infectious uveitis) Ankylosing spondylitis; Cancer PCSK9 (proprotein convertase subtilisin/kexin coronary heart disease Alirocumab type 9) (CHD) or high risk of CHD REGN727 hyperlipidaemia LY3015014 hypercholesterolaemia stroke atherosclerosis a cardiovascular disease or condition a condition associated with elevated LDL NGF Osteoarthritis Fasinumab Pain REGN475 IL-4 receptor alpha Allergic asthma Dupilumab eosinophilic asthma REGN668 IL-13 receptor Atopic dermatitis delta-like ligand-4 (Dll4) Cancer Enoticumab REGN421 angiopoietin-2 (Ang2) Cancer Nesvacumab REGN910 GDF8 Metabolic disorder REGN1033 cancer, obesity, diabetes, LY2495655 arthritis, multiple sclerosis, muscular dystrophy, amyotrophic lateral sclerosis, Parkinson's disease, osteoporosis, osteoarthritis, osteopenia, metabolic syndromes (including, but not limited to diabetes, obesity, nutritional disorders, organ atrophy, chronic obstructive pulmonary disease and anorexia) Disuse muscle atrophy cancer-related cachexia ERBB3 Cancer REGN1400 angiopoietin-1 (Ang1) Cancer, eg, ovarian cancer AMG386 angiopoietin-1 (Ang2) VEGF receptor Cancer Motesanib PDGF receptor NSCLC AMG 706 Stem cell factor receptor Breast cancer Thyroid cancer type 1 insulin-like growth factor receptor Cancer Ganitumab (IGF1R) Breast cancer Linsitinib Pancreatic cancer ASP7487 hepatocyte growth factor (HGF) Cancer Rilotumumab Breast cancer Pancreatic cancer HER3 Cancer AMG 888 ErbB3 Breast cancer U3-1287 Pancreatic cancer IL-17 receptor Inflammatory disease AMG 827 Asthma brodalumab Psoriasis sclerostin Bone-related condition AMG 785 postmenopausal CDP7851 osteoporosis fracture healing glucokinase Diabetes AMG 151 ARRY-403 PCSK9 (proprotein convertase subtilisin/kexin coronary heart disease AMG 145 type 9) (CHD) or high risk of CHD Evolocumab hyperlipidaemia hypercholesterolaemia stroke atherosclerosis a cardiovascular disease or condition a condition associated with elevated LDL VLA 2 Inflammatory bowel SAR339658 Integrin α2β1 disease IL-4 Idiopathic pulmonary SAR156597 IL-13 fibrosis lysophosphatidic acid receptor Systemic sclerosis SAR100842 LPA-1 fibrosis LPA-3 Androgen receptor Cancer, eg, prostate cancer, MDV3100 breast cancer enzalutamide HER1 Cancer, eg, NSCLC Erlotinib EGFR ERBITUX ™ VECTIBIX ™ VEGF receptor 1 Cancer, eg, colorectal ASP4130 VEGF receptor 2 cancer, breast cancer tivozanib VEGF receptor 3 JAK Inflammatory disease, eg, ASP015K JAK1 rheumatoid arthritis Baricitinib JAK2 Diabetic nephropathy CD40 Prevention of organ ASP1240 transplant rejection GnRH Endometriosis ASP1707 Cancer, eg, prostate cancer degarelix PDE9 Lower unirary tract ASP4901 symptoms associated with benign prostatic hyperplasia TNF alpha Inflammatory disease, eg, Certolizumab pegol rheumatoid arthritis, psoriasis, chrohn's disease, IBD Programmed cell death protein 1 Cancer Nivolumab Chronic myelocytic MK-3475 leukemia; Hepatitis C virus infection; Hepatocellular carcinoma; Hodgkins disease; Melanoma; Multiple myeloma; Non- Hodgkin lymphoma; Non- small-cell lung cancer; Renal cell carcinoma; Solid tumor; Stage IV melanoma Hepatocyte growth factor Cancer onartuzumab MET Glioblastoma; Hepatocellular carcinoma; Metastatic colorectal cancer; Metastatic non small cell lung cancer; Metastatic stomach cancer; Non-small-cell lung cancer Angiopoietin ligand-1 Breast tumor; Cancer; trebananib Angiopoietin ligand-2 Colorectal tumor; Fallopian Tek tyrosine kinase receptor tube cancer; Gastrointestinal tumor; Glioblastoma; Hepatocellular carcinoma; Metastatic esophageal cancer; Metastatic gastrointestinal cancer; Metastatic non small cell lung cancer; Metastatic ovary cancer; Metastatic renal cancer; Ovary tumor; Peritoneal tumor; Transitional cell carcinoma CD37 modulator Cancer elotuzumab Lymphocyte function antigen-3 receptor Multiple myeloma SLAM family member 7 IL-2 Multiple sclerosis daclizumab IL-2 receptor alpha EGFR Cancer necitumumab Metastatic non small cell lung cancer; Solid tumor IL-5 Asthma; Eosinophilic reslizumab esophagitis B-lymphocyte cell adhesion molecule Cancer, eg Acute Inotuzumab CD22 lymphoblastic leukemia; inotuzumab ozogamicin Follicle center lymphoma; epratuzumab Non-Hodgkin lymphoma; moxetumomab Systemic lupus moxetumomab pasudotox erythematosus, hairy cell leukaemia IL1 beta Acne vulgaris; gevokizumab Atherosclerosis; Behcets disease; Cardiovascular disease; Dermatomyositis; Insulin dependent diabetes; Multiple myeloma; Osteoarthritis; Paraproteinemia; Polymyositis; Pyoderma gangrenosum; Scleritis; Uveitis CD20 Cancer Ocrelizumab Multiple sclerosis ofatumumab follicular lymphoma (eg, refractory or relapsed) diffuse large B cell lymphoma (eg, relapsed) chronic lymphocytic leukaemia (eg, first line therapy or relapsed) IL-23 Crohns disease; tildrakizumab Inflammatory disease; Psoriasis BAFF Autoimmune disease Belimumab Neutrokine alpha systemic lupus Benlysta ™ erythematosus Tabalumab Multiple myeloma vasculitis IL5 Asthma mepolizumab IL6 Inflammatory disease sirukumab rheumatoid arthritis Lp-PLA2 Atherosclerosis darapladib diabetic macular oedema CCR9 chemokine receptor Inflammatory disease Vercirnon rheumatoid arthritis Crohn's disease DOPA decarboxylase Parkinson's Disease Patrome Her2 Cancer, eg, gastric cancer, Tyverb ™ EGFR breast cancer, head and Tykerb ™ neck squamous cell cancer, lapatinib ADP receptor Cardiovascular disease or Brilinta condition Brilique Thrombosis, eg, arterial thrombosis VEGFR Cancer, eg, Caprelsa EGFR medullary thyroid cancer LABA Respiratory disease or PT003 GFF LAMA condition, eg, COPD Factor Xa thromboembolism apixaban Oxelumab OX40 ligand Asthma Graft-versus-host disease Tremelimumab CTLA-4 Cancer, eg, melanoma Ticilimumab CD152 Autoimmune disease ipilimumab MPDL3280A PD-L1 Cancer, eg, solid tumour, MEDI4736 kidney cancer, lung cancer, melanoma, NSCLC, multiple myeloma Autoimmune disease Nivolumab PD-1 Cancer, eg, solid tumour, AMP-514 kidney cancer, lung cancer, AMP-224 melanoma, NSCLC, multiple myeloma Autoimmune disease LIGHT TNFSF14 CD40 ligand JAK Inflammatory disease, eg, tofacitinib rheumatoid arthritis, psoriasis, chrohn's disease, IBD, ulcerative colitis, Psoriatic Arthritis Nerve Growth Factor Pain tanezumab Osteoarthritis pain Her1 receptor Cancer, eg, Non-Small Cell dacomitinib Her2 receptor Lung Cancer Her4 receptor c-MET Cancer, eg, Non-Small Cell crizotinib ALK Lung Cancer Programmed cell death 1 receptor Cancer, eg, renal cell Nivolumab carcinoma SLAMF7 Cancer, eg, multiple Elotuzumab CD319 myeloma CD30 Cancer, eg, Hodgkin Brentuximab lymphoma, systemic Brentuximab vedotin anaplastic large cell lymphoma, T-cell lymphoma GPR40 Diabetes, eg, diabetes Fasiglifam DPP-4 mellitus trelagliptin VEFGR-1 receptor Cancer, eg, non-squamous Motesanib VEFGR-2 receptor non-small cell lung cancer Motesanib diphosphate VEFGR-3 receptor PDGFR cKit amyloid ß Alzheimer's disease Solanezumab TNF alpha Inflammatory disease, eg, SIMPONI ™ rheumatoid arthritis, HUMIRA ™ psoriasis, chrohn's disease, REMICADE ™ IBD, ulcerative colitis, ENBREL ™ Psoriatic Arthritis Adalimumab IL-21 Autoimmune disease or Agonist or antagonist condition antibody specific for Inflammatory disease or human IL-21 condition NNC0114-0005 Rheumatoid arthritis NNC0114-0006 Crohn's disease NN8828 IBD ATR-107 Ulcerative colitis Said or an anti-IL-21 Systemic lupus antibody in combination erythematosus (SLE) with an agent selected from Graft versus host disease the group consisting of Cancer ipilimumab (eg, to treat Metastatic melanoma melanoma), an anti-PD1 Renal cell carcinoma antibody (eg, to treat solid Melanoma tumours), sunitinib (eg, to Solid tumours treat renal cell carcinoma), Acute myeloid leukaemia rituximab (eg, to treat Non- Non-Hodgkin's lymphoma Hodgkin's lymphoma), Ovarian cancer sorafenib (eg, to treat renal Colorectal cancer cell carcinoma), doxorubicin (eg, to treat ovarian cancer) and cetuximab (eg, to treat colorectal cancer).","TABLE 6 PCSK9 SEQUENCES SEQ ID FORM/ALLELE VERSION SEQUENCE NO: AMINO ACID SEQUENCES Italics = signal sequence 1-30 Courier = pro peptide 31-152 lower case = catalytic domain 153-449 UPPER CASE = C-terminal domain 450-692 Underlined = residues changed from allele a in other sequences (aa residue number shown) a Pro-Form with 46 53 1 Signal Sequence MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELAILKLPM VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylidtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllpiaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtigtigtnfgrcvdlfapgedllgassdcstcfvsqsgtsqaaahvagiaammisaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPCIANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ a Pro-Form QEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP 2 WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryadeyqppdggslvevylidtslqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqivqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtigtigtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrllhfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ a Mature form sipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg 3 thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvtvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgedllgassdcstcfvsqsgtsqaaahvaglaammlsaepeltlaelrqrllhfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ f Pro-Form with 46 53 Signal Sequence MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP 4 WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ f Pro-Form QEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP 5 WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnlerltppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrsirvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgedllgassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ f, p, aj Mature form sipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg 6 thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ c Pro-Form with 46 53 7 MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvincqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqriaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammisaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEGAVTAVAICCRSRHLAQASQELQ c Pro-Form QEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP 8 WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnlerltppryradeyqppdggslvevyiidtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvinaacqriaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtigtigtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEGAVTAVAICCRSRHLAQASQELQ c, q Mature form sipwnleritppryradeyqppdggslvevylidtsiqsdhrelegrvmvtdfenvpeedgtrfhrqaskcdshg 9 thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEGAVTAVAICCRSRHLAQASQELQ r Pro-Form with 46 53 10 Signal Sequence MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtigtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEGAVTAVAICCRSRHLAQASQELQ r Pro-Form QEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP 11 WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvaglaammlsaepeltlaelrgrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEGAVTAVAICCRSRHLAQASQELQ r Mature form sipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg 12 thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvaglaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEGAVTAVAICCRSRHLAQASQELQ p Pro-Form with 46 53 13 Signal Sequence MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLVEAPEHGTTATFHRCAKDP WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvaglaammlsaepeltlaelrqrflhfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ p Pro-Form QEDEDGDYEELVLALRSEEDGLVEAPEHGTTATFHRCAKDP 14 WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPM VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ m Pro-Form with 46 53 15 Signal Sequence MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvatlppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ m Pro-Form QEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP 16 WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvatlppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ m Mature form sipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg 17 thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvatlppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ e Pro-Form with 46 53 18 Signal Sequence MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtigtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dviseawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ e Pro-Form QEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP 19 WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dviseawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ e Mature form sipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg 20 thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dviseawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ h Pro-Form with 46 53 21 Signal Sequence MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtigtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvatlppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPPEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ h Pro-Form QEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP 22 WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvatlppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPPEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ h Mature form sipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg 23 thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvatlppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPPEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ aj Pro-Form with 46 53 24 Signal Sequence MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALLSEEDGLAEAPEHGTTATFHRCAKDP WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtigtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ aj Pro-Form QEDEDGDYEELVLALLSEEDGLAEAPEHGTTATFHRCAKDP 25 WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ q Pro-Form with 46 53 26 Signal Sequence MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLVEAPEHGTTATFHRCAKDP WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtigtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEGAVTAVAICCRSRHLAQASQELQ q Pro-Form QEDEDGDYEELVLALRSEEDGLVEAPEHGTTATFHRCAKDP 27 WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEGAVTAVAICCRSRHLAQASQELQ NUCLEOTIDE SEQUENCES Italics = nucleotide sequence encoding signal sequence (nucleotides 1-90) Courier = nucleotide sequence encoding pro peptide (nucleotides 91-456) lower case = nucleotide sequence encoding catalytic domain (nucleotides 457-1346) UPPER CASE = nucleotide sequence encoding C-terminal domain (nucleotides 1347-2076) a ATGGGCACCGTCAGCTCCAGGCGGTCCTGGTGGCCGCTGCCACTGCTGCTGCTGCTGCTGCTGCTCCTGGGTC 28 R46L CGT to CTT CCGCGGGCGCCCGTGCGCAGGAGGACGAGGACGGCGACTACGAGGAGCTGGTGCTAGCCTTGCGTTCCG A53V GCC to GTC AGGAGGACGGCCTGGCCGAAGCACCCGAGCACGGAACCACAGCCACCTTCCACCGCTGCGCCAAGGAT CCGTGGAGGTTGCCTGGCACCTACGTGGTGGTGCTGAAGGAGGAGACCCACCTCTCGCAGTCAGAGCG CACTGCCCGCCGCCTGCAGGCCCAGGCTGCCCGCCGGGGATACCTCACCAAGATCCTGCATGTCTTCC ATGGCCTTCTTCCTGGCTTCCTGGTGAAGATGAGTGGCGACCTGCTGGAGCTGGCCTTGAAGTTGCCC CATGTCGACTACATCGAGGAGGACTCCTCTGTCTTTGCCCAGagcatcccgtggaacctggagcggattacccctcca cggtaccgggcggatgaataccagccccccgacggaggcagcctggtggaggtgtatctcctagacaccagcatacagagtgaccaccgggaa atcgagggcagggtcatggtcaccgacttcgagaatgtgcccgaggaggacgggacccgcttccacagacaggccagcaagtgtgacagtcat ggcacccacctggcaggggtggtcagcggccgggatgccggcgtggccaagggtgccagcatgcgcagcctgcgcgtgctcaactgccaaggg aagggcacggttagcggcaccctcataggcctggagtttattcggaaaagccagctggtccagcctgtggggccactggtggtgctgctgcccct ggcgggtgggtacagccgcgtcctcaacgccgcctgccagcgcctggcgagggctggggtcgtgctggtcaccgctgccggcaacttccgggac gatgcctgcctctactccccagcctcagctcccgaggtcatcacagttggggccaccaatgcccaagaccagccggtgaccctggggactttggg gaccaactttggccgctgtgtggacctctttgccccaggggaggacatcattggtgcctccagcgactgcagcacctgctttgtgtcacagagtgg gacatcacaggctgctgcccacgtggctggcattgcagccatgatgctgctgccgagccggagctaccctggccgagttgaggcagagactg N425S AAT to AGT A443T GCC to ACC atccacttctctgccaaagatgtcatcaatgaggcctggttccctgaggaccagcgggtactgacccccaacctggtggccgccctgccccccag cacccatGGGGCAGGTTGGCAGCTGTTTTGCAGGACTGTATGGTCAGCACACTCGGGGCCTACACGGATGGCC I474V ATC to GTC ACAGCCATCGCCCGCTGCGCCCCAGATGAGGAGCTGCTGAGCTGCTCCAGTTTCTCCAGGAGTGGGAAGCGG CGGGGCGAGCGCATGGAGGCCCAAGGGGGCAAGCTGGTCTGCCGGGCCCACAACGCTTTTGGGGGTGAGGG TGTCTACGCCATTGCCAGGTGCTGCCTGCTACCCCAGGCCAACTGCAGCGTCCACACAGCTCCACCAGCTGAG GCCAGCATGGGGACCCGTGTCCACTGCCACCAACAGGGCCACGTCCTCACAGGCTGCAGCTCCCACTGGGAG GTGGAGGACCTTGGCACCCACAAGCCGCCTGTGCTGAGGCCACGAGGTCAGCCCAACCAGTGCGTGGGCCAC AGGGAGGCCAGCATCCACGCTTCCTGCTGCCATGCCCCAGGTCTGGAATGCAAAGTCAAGGAGCATGGAA Q619P CAG to CCG E620G GAG to GGG TCCCGGCCCCTCAGGAGCAGGTGACCGTGGCCTGCGAGGAGGGCTGGACCCTGACTGGCTGCAGTGCCCTCC CTGGGACCTCCCACGTCCTGGGGGCCTACGCCGTAGACAACACGTGTGTAGTCAGGAGCCGGGACGTCAGCA E670G GAG to GGG CTACAGGCAGCACCAGCGAAGAGGCCGTGACAGCCGTTGCCATCTGCTGCCGGAGCCGGCACCTGGCGCAGG CCTCCCAGGAGCTCCAGTGAC f ATGGGCACCGTCAGCTCCAGGCGGTCCTGGTGGCCGCTGCCACTGCTGCTGCTGCTGCTGCTGCTCCTGGGTC 29 R46L CGT to CTT CCGCGGGCGCCCGTGCGCAGGAGGACGAGGACGGCGACTACGAGGAGCTGGTGCTAGCCTTGCGTTCCG A53V GCC to GTC AGGAGGACGGCCTGGCCGAAGCACCCGAGCACGGAACCACAGCCACCTTCCACCGCTGCGCCAAGGAT CCGTGGAGGTTGCCTGGCACCTACGTGGTGGTGCTGAAGGAGGAGACCCACCTCTCGCAGTCAGAGCG CACTGCCCGCCGCCTGCAGGCCCAGGCTGCCCGCCGGGGATACCTCACCAAGATCCTGCATGTCTTCC ATGGCCTTCTTCCTGGCTTCCTGGTGAAGATGAGTGGCGACCTGCTGGAGCTGGCCTTGAAGTTGCCC CATGTCGACTACATCGAGGAGGACTCCTCTGTCTTTGCCCAGagcatcccgtggaacctggagcggattacccctcca cggtaccgggcggatgaataccagccccccgacggaggcagcctggtggaggtgtatctcctagacaccagcatacagagtgaccaccgggaa atcgagggcagggtcatggtcaccgacttcgagaatgtgcccgaggaggacgggacccgcttccacagacaggccagcaagtgtgacagtcat ggcacccacctggcaggggtggtcagcggccgggatgccggcgtggccaagggtgccagcatgcgcagcctgcgcgtgctcaactgccaaggg aagggcacggttagcggcaccctcataggcctggagtttattcggaaaagccagctggtccagcctgtggggccactggtggtgctgctgcccct ggcgggtgggtacagccgcgtcctcaacgccgcctgccagcgcctggcgagggctggggtcgtgctggtcaccgctgccggcaacttccgggac gatgcctgcctctactccccagcctcagctcccgaggtcatcacagttggggccaccaatgcccaagaccagccggtgaccctggggactttggg gaccaactttggccgctgtgtggacctctttgccccaggggaggacatcattggtgcctccagcgactgcagcacctgctttgtgtcacagagtgg gacatcacaggctgctgcccacgtggctggcattgcagccatgatgctgctgccgagccggagctaccctggccgagttgaggcagagactg N425S AAT to AGT A443T GCC to ACC atccacttctctgccaaagatgtcatcaatgaggcctggttccctgaggaccagcgggtactgacccccaacctggtggccgccctgccccccag cacccatGGGGCAGGTTGGCAGCTGTTTTGCAGGACTGTATGGTCAGCACACTCGGGGCCTACACGGATGGCC I474V ATC to GTC ACAGCCGTCGCCCGCTGCGCCCCAGATGAGGAGCTGCTGAGCTGCTCCAGTTTCTCCAGGAGTGGGAAGCGG CGGGGCGAGCGCATGGAGGCCCAAGGGGGCAAGCTGGTCTGCCGGGCCCACAACGCTTTTGGGGGTGAGGG TGTCTACGCCATTGCCAGGTGCTGCCTGCTACCCCAGGCCAACTGCAGCGTCCACACAGCTCCACCAGCTGAG GCCAGCATGGGGACCCGTGTCCACTGCCACCAACAGGGCCACGTCCTCACAGGCTGCAGCTCCCACTGGGAG GTGGAGGACCTTGGCACCCACAAGCCGCCTGTGCTGAGGCCACGAGGTCAGCCCAACCAGTGCGTGGGCCAC AGGGAGGCCAGCATCCACGCTTCCTGCTGCCATGCCCCAGGTCTGGAATGCAAAGTCAAGGAGCATGGAA Q619P CAG to CCG E620G GAG to GGG TCCCGGCCCCTCAGGAGCAGGTGACCGTGGCCTGCGAGGAGGGCTGGACCCTGACTGGCTGCAGTGCCCTCC CTGGGACCTCCCACGTCCTGGGGGCCTACGCCGTAGACAACACGTGTGTAGTCAGGAGCCGGGACGTCAGCA E670G GAG to GGG CTACAGGCAGCACCAGCGAAGAGGCCGTGACAGCCGTTGCCATCTGCTGCCGGAGCCGGCACCTGGCGCAGG CCTCCCAGGAGCTCCAGTGAC c ATGGGCACCGTCAGCTCCAGGCGGTCCTGGTGGCCGCTGCCACTGCTGCTGCTGCTGCTGCTGCTCCTGGGTC 30 R46L CGT to CTT CCGCGGGCGCCCGTGCGCAGGAGGACGAGGACGGCGACTACGAGGAGCTGGTGCTAGCCTTGCGTTCCG A53V GCC to GTC AGGAGGACGGCCTGGCCGAAGCACCCGAGCACGGAACCACAGCCACCTTCCACCGCTGCGCCAAGGAT CCGTGGAGGTTGCCTGGCACCTACGTGGTGGTGCTGAAGGAGGAGACCCACCTCTCGCAGTCAGAGCG CACTGCCCGCCGCCTGCAGGCCCAGGCTGCCCGCCGGGGATACCTCACCAAGATCCTGCATGTCTTCC ATGGCCTTCTTCCTGGCTTCCTGGTGAAGATGAGTGGCGACCTGCTGGAGCTGGCCTTGAAGTTGCCC CATGTCGACTACATCGAGGAGGACTCCTCTGTCTTTGCCCAGagcatcccgtggaacctggagcggattacccctcca cggtaccgggcggatgaataccagccccccgacggaggcagcctggtggaggtgtatctcctagacaccagcatacagagtgaccaccgggaa atcgagggcagggtcatggtcaccgacttcgagaatgtgcccgaggaggacgggacccgcttccacagacaggccagcaagtgtgacagtcat ggcacccacctggcaggggtggtcagcggccgggatgccggcgtggccaagggtgccagcatgcgcagcctgcgcgtgctcaactgccaaggg aagggcacggttagcggcaccctcataggcctggagtttattcggaaaagccagctggtccagcctgtggggccactggtggtgctgctgcccct ggcgggtgggtacagccgcgtcctcaacgccgcctgccagcgcctggcgagggctggggtcgtgctggtcaccgctgccggcaacttccgggac gatgcctgcctctactccccagcctcagctcccgaggtcatcacagttggggccaccaatgcccaagaccagccggtgaccctggggactttggg gaccaactttggccgctgtgtggacctctttgccccaggggaggacatcattggtgcctccagcgactgcagcacctgctttgtgtcacagagtgg gacatcacaggctgctgcccacgtggctggcattgcagccatgatgctgctgccgagccggagctaccctggccgagttgaggcagagactg N425S AAT to AGT A443T GCC to ACC atccacttctctgccaaagatgtcatcaatgaggcctggttccctgaggaccagcgggtactgacccccaacctggtggccgccctgccccccag cacccatGGGGCAGGTTGGCAGCTGTTTTGCAGGACTGTATGGTCAGCACACTCGGGGCCTACACGGATGGCC I474V ATC to GTC ACAGCCATCGCCCGCTGCGCCCCAGATGAGGAGCTGCTGAGCTGCTCCAGTTTCTCCAGGAGTGGGAAGCGG CGGGGCGAGCGCATGGAGGCCCAAGGGGGCAAGCTGGTCTGCCGGGCCCACAACGCTTTTGGGGGTGAGGG TGTCTACGCCATTGCCAGGTGCTGCCTGCTACCCCAGGCCAACTGCAGCGTCCACACAGCTCCACCAGCTGAG GCCAGCATGGGGACCCGTGTCCACTGCCACCAACAGGGCCACGTCCTCACAGGCTGCAGCTCCCACTGGGAG GTGGAGGACCTTGGCACCCACAAGCCGCCTGTGCTGAGGCCACGAGGTCAGCCCAACCAGTGCGTGGGCCAC AGGGAGGCCAGCATCCACGCTTCCTGCTGCCATGCCCCAGGTCTGGAATGCAAAGTCAAGGAGCATGGAA Q619P CAG to CCG E620G GAG to GGG TCCCGGCCCCTCAGGAGCAGGTGACCGTGGCCTGCGAGGAGGGCTGGACCCTGACTGGCTGCAGTGCCCTCC CTGGGACCTCCCACGTCCTGGGGGCCTACGCCGTAGACAACACGTGTGTAGTCAGGAGCCGGGACGTCAGCA E670G GAG to GGG CTACAGGCAGCACCAGCGAAGGGGCCGTGACAGCCGTTGCCATCTGCTGCCGGAGCCGGCACCTGGCGCAGG CCTCCCAGGAGCTCCAGTGAC r ATGGGCACCGTCAGCTCCAGGCGGTCCTGGTGGCCGCTGCCACTGCTGCTGCTGCTGCTGCTGCTCCTGGGTC 31 R46L CGT to CTT CCGCGGGCGCCCGTGCGCAGGAGGACGAGGACGGCGACTACGAGGAGCTGGTGCTAGCCTTGCGTTCCG A53V GCC to GTC AGGAGGACGGCCTGGCCGAAGCACCCGAGCACGGAACCACAGCCACCTTCCACCGCTGCGCCAAGGAT CCGTGGAGGTTGCCTGGCACCTACGTGGTGGTGCTGAAGGAGGAGACCCACCTCTCGCAGTCAGAGCG CACTGCCCGCCGCCTGCAGGCCCAGGCTGCCCGCCGGGGATACCTCACCAAGATCCTGCATGTCTTCC ATGGCCTTCTTCCTGGCTTCCTGGTGAAGATGAGTGGCGACCTGCTGGAGCTGGCCTTGAAGTTGCCC CATGTCGACTACATCGAGGAGGACTCCTCTGTCTTTGCCCAGagcatcccgtggaacctggagcggattacccctcca cggtaccgggcggatgaataccagccccccgacggaggcagcctggtggaggtgtatctcctagacaccagcatacagagtgaccaccgggaa atcgagggcagggtcatggtcaccgacttcgagaatgtgcccgaggaggacgggacccgcttccacagacaggccagcaagtgtgacagtcat ggcacccacctggcaggggtggtcagcggccgggatgccggcgtggccaagggtgccagcatgcgcagcctgcgcgtgctcaactgccaaggg aagggcacggttagcggcaccctcataggcctggagtttattcggaaaagccagctggtccagcctgtggggccactggtggtgctgctgcccct ggcgggtgggtacagccgcgtcctcaacgccgcctgccagcgcctggcgagggctggggtcgtgctggtcaccgctgccggcaacttccgggac gatgcctgcctctactccccagcctcagctcccgaggtcatcacagttggggccaccaatgcccaagaccagccggtgaccctggggactttggg gaccaactttggccgctgtgtggacctctttgccccaggggaggacatcattggtgcctccagcgactgcagcacctgctttgtgtcacagagtgg gacatcacaggctgctgcccacgtggctggcattgcagccatgatgctgctgccgagccggagctaccctggccgagttgaggcagagactg N425S AAT to AGT A443T GCC to ACC atccacttctctgccaaagatgtcatcaatgaggcctggttccctgaggaccagcgggtactgacccccaacctggtggccgccctgccccccag cacccatGGGGCAGGTTGGCAGCTGTTTTGCAGGACTGTATGGTCAGCACACTCGGGGCCTACACGGATGGCC I474V ATC to GTC ACAGCCGTCGCCCGCTGCGCCCCAGATGAGGAGCTGCTGAGCTGCTCCAGTTTCTCCAGGAGTGGGAAGCGG CGGGGCGAGCGCATGGAGGCCCAAGGGGGCAAGCTGGTCTGCCGGGCCCACAACGCTTTTGGGGGTGAGGG TGTCTACGCCATTGCCAGGTGCTGCCTGCTACCCCAGGCCAACTGCAGCGTCCACACAGCTCCACCAGCTGAG GCCAGCATGGGGACCCGTGTCCACTGCCACCAACAGGGCCACGTCCTCACAGGCTGCAGCTCCCACTGGGAG GTGGAGGACCTTGGCACCCACAAGCCGCCTGTGCTGAGGCCACGAGGTCAGCCCAACCAGTGCGTGGGCCAC AGGGAGGCCAGCATCCACGCTTCCTGCTGCCATGCCCCAGGTCTGGAATGCAAAGTCAAGGAGCATGGAA Q619P CAG to CCG E620G GAG to GGG TCCCGGCCCCTCAGGAGCAGGTGACCGTGGCCTGCGAGGAGGGCTGGACCCTGACTGGCTGCAGTGCCCTCC CTGGGACCTCCCACGTCCTGGGGGCCTACGCCGTAGACAACACGTGTGTAGTCAGGAGCCGGGACGTCAGCA E670G GAG to GGG CTACAGGCAGCACCAGCGAAGGGGCCGTGACAGCCGTTGCCATCTGCTGCCGGAGCCGGCACCTGGCGCAGG CCTCCCAGGAGCTCCAGTGAC p ATGGGCACCGTCAGCTCCAGGCGGTCCTGGTGGCCGCTGCCACTGCTGCTGCTGCTGCTGCTGCTCCTGGGTC 32 R46L CGT to CTT CCGCGGGCGCCCGTGCGCAGGAGGACGAGGACGGCGACTACGAGGAGCTGGTGCTAGCCTTGCGTTCCG A53V GCC to GTC AGGAGGACGGCCTGGTCGAAGCACCCGAGCACGGAACCACAGCCACCTTCCACCGCTGCGCCAAGGAT CCGTGGAGGTTGCCTGGCACCTACGTGGTGGTGCTGAAGGAGGAGACCCACCTCTCGCAGTCAGAGCG CACTGCCCGCCGCCTGCAGGCCCAGGCTGCCCGCCGGGGATACCTCACCAAGATCCTGCATGTCTTCC ATGGCCTTCTTCCTGGCTTCCTGGTGAAGATGAGTGGCGACCTGCTGGAGCTGGCCTTGAAGTTGCCC CATGTCGACTACATCGAGGAGGACTCCTCTGTCTTTGCCCAGagcatcccgtggaacctggagcggattacccctcca cggtaccgggcggatgaataccagccccccgacggaggcagcctggtggaggtgtatctcctagacaccagcatacagagtgaccaccgggaa atcgagggcagggtcatggtcaccgacttcgagaatgtgcccgaggaggacgggacccgcttccacagacaggccagcaagtgtgacagtcat ggcacccacctggcaggggtggtcagcggccgggatgccggcgtggccaagggtgccagcatgcgcagcctgcgcgtgctcaactgccaaggg aagggcacggttagcggcaccctcataggcctggagtttattcggaaaagccagctggtccagcctgtggggccactggtggtgctgctgcccct ggcgggtgggtacagccgcgtcctcaacgccgcctgccagcgcctggcgagggctggggtcgtgctggtcaccgctgccggcaacttccgggac gatgcctgcctctactccccagcctcagctcccgaggtcatcacagttggggccaccaatgcccaagaccagccggtgaccctggggactttggg gaccaactttggccgctgtgtggacctctttgccccaggggaggacatcattggtgcctccagcgactgcagcacctgctttgtgtcacagagtgg gacatcacaggctgctgcccacgtggctggcattgcagccatgatgctgctgccgagccggagctaccctggccgagttgaggcagagactg N425S AAT to AGT A443T GCC to ACC atccacttctctgccaaagatgtcatcaatgaggcctggttccctgaggaccagcgggtactgacccccaacctggtggccgccctgccccccag cacccatGGGGCAGGTTGGCAGCTGTTTTGCAGGACTGTATGGTCAGCACACTCGGGGCCTACACGGATGGCC I474V ATC to GTC ACAGCCGTCGCCCGCTGCGCCCCAGATGAGGAGCTGCTGAGCTGCTCCAGTTTCTCCAGGAGTGGGAAGCGG CGGGGCGAGCGCATGGAGGCCCAAGGGGGCAAGCTGGTCTGCCGGGCCCACAACGCTTTTGGGGGTGAGGG TGTCTACGCCATTGCCAGGTGCTGCCTGCTACCCCAGGCCAACTGCAGCGTCCACACAGCTCCACCAGCTGAG GCCAGCATGGGGACCCGTGTCCACTGCCACCAACAGGGCCACGTCCTCACAGGCTGCAGCTCCCACTGGGAG GTGGAGGACCTTGGCACCCACAAGCCGCCTGTGCTGAGGCCACGAGGTCAGCCCAACCAGTGCGTGGGCCAC AGGGAGGCCAGCATCCACGCTTCCTGCTGCCATGCCCCAGGTCTGGAATGCAAAGTCAAGGAGCATGGAA Q619P CAG to CCG E620G GAG to GGG TCCCGGCCCCTCAGGAGCAGGTGACCGTGGCCTGCGAGGAGGGCTGGACCCTGACTGGCTGCAGTGCCCTCC CTGGGACCTCCCACGTCCTGGGGGCCTACGCCGTAGACAACACGTGTGTAGTCAGGAGCCGGGACGTCAGCA E670G GAG to GGG CTACAGGCAGCACCAGCGAAGAGGCCGTGACAGCCGTTGCCATCTGCTGCCGGAGCCGGCACCTGGCGCAGG CCTCCCAGGAGCTCCAGTGAC m ATGGGCACCGTCAGCTCCAGGCGGTCCTGGTGGCCGCTGCCACTGCTGCTGCTGCTGCTGCTGCTCCTGGGTC 33 R46L CGT to CTT CCGCGGGCGCCCGTGCGCAGGAGGACGAGGACGGCGACTACGAGGAGCTGGTGCTAGCCTTGCGTTCCG A53V GCC to GTC AGGAGGACGGCCTGGCCGAAGCACCCGAGCACGGAACCACAGCCACCTTCCACCGCTGCGCCAAGGAT CCGTGGAGGTTGCCTGGCACCTACGTGGTGGTGCTGAAGGAGGAGACCCACCTCTCGCAGTCAGAGCG CACTGCCCGCCGCCTGCAGGCCCAGGCTGCCCGCCGGGGATACCTCACCAAGATCCTGCATGTCTTCC ATGGCCTTCTTCCTGGCTTCCTGGTGAAGATGAGTGGCGACCTGCTGGAGCTGGCCTTGAAGTTGCCC CATGTCGACTACATCGAGGAGGACTCCTCTGTCTTTGCCCAGagcatcccgtggaacctggagcggattacccctcca cggtaccgggcggatgaataccagccccccgacggaggcagcctggtggaggtgtatctcctagacaccagcatacagagtgaccaccgggaa atcgagggcagggtcatggtcaccgacttcgagaatgtgcccgaggaggacgggacccgcttccacagacaggccagcaagtgtgacagtcat ggcacccacctggcaggggtggtcagcggccgggatgccggcgtggccaagggtgccagcatgcgcagcctgcgcgtgctcaactgccaaggg aagggcacggttagcggcaccctcataggcctggagtttattcggaaaagccagctggtccagcctgtggggccactggtggtgctgctgcccct ggcgggtgggtacagccgcgtcctcaacgccgcctgccagcgcctggcgagggctggggtcgtgctggtcaccgctgccggcaacttccgggac gatgcctgcctctactccccagcctcagctcccgaggtcatcacagttggggccaccaatgcccaagaccagccggtgaccctggggactttggg gaccaactttggccgctgtgtggacctctttgccccaggggaggacatcattggtgcctccagcgactgcagcacctgctttgtgtcacagagtgg gacatcacaggctgctgcccacgtggctggcattgcagccatgatgctgctgccgagccggagctaccctggccgagttgaggcagagactg N425S AAT to AGT A443T GCC to ACC atccacttctctgccaaagatgtcatcaatgaggcctggttccctgaggaccagcgggtactgacccccaacctggtggccaccctgccccccag cacccatGGGGCAGGTTGGCAGCTGTTTTGCAGGACTGTATGGTCAGCACACTCGGGGCCTACACGGATGGCC I474V ATC to GTC ACAGCCATCGCCCGCTGCGCCCCAGATGAGGAGCTGCTGAGCTGCTCCAGTTTCTCCAGGAGTGGGAAGCGG CGGGGCGAGCGCATGGAGGCCCAAGGGGGCAAGCTGGTCTGCCGGGCCCACAACGCTTTTGGGGGTGAGGG TGTCTACGCCATTGCCAGGTGCTGCCTGCTACCCCAGGCCAACTGCAGCGTCCACACAGCTCCACCAGCTGAG GCCAGCATGGGGACCCGTGTCCACTGCCACCAACAGGGCCACGTCCTCACAGGCTGCAGCTCCCACTGGGAG GTGGAGGACCTTGGCACCCACAAGCCGCCTGTGCTGAGGCCACGAGGTCAGCCCAACCAGTGCGTGGGCCAC AGGGAGGCCAGCATCCACGCTTCCTGCTGCCATGCCCCAGGTCTGGAATGCAAAGTCAAGGAGCATGGAA Q619P CAG to CCG E620G GAG to GGG TCCCGGCCCCTCAGGAGCAGGTGACCGTGGCCTGCGAGGAGGGCTGGACCCTGACTGGCTGCAGTGCCCTCC CTGGGACCTCCCACGTCCTGGGGGCCTACGCCGTAGACAACACGTGTGTAGTCAGGAGCCGGGACGTCAGCA E670G GAG to GGG CTACAGGCAGCACCAGCGAAGAGGCCGTGACAGCCGTTGCCATCTGCTGCCGGAGCCGGCACCTGGCGCAGG CCTCCCAGGAGCTCCAGTGAC e ATGGGCACCGTCAGCTCCAGGCGGTCCTGGTGGCCGCTGCCACTGCTGCTGCTGCTGCTGCTGCTCCTGGGTC 34 R46L CGT to CTT CCGCGGGCGCCCGTGCGCAGGAGGACGAGGACGGCGACTACGAGGAGCTGGTGCTAGCCTTGCGTTCCG A53V GCC to GTC AGGAGGACGGCCTGGCCGAAGCACCCGAGCACGGAACCACAGCCACCTTCCACCGCTGCGCCAAGGAT CCGTGGAGGTTGCCTGGCACCTACGTGGTGGTGCTGAAGGAGGAGACCCACCTCTCGCAGTCAGAGCG CACTGCCCGCCGCCTGCAGGCCCAGGCTGCCCGCCGGGGATACCTCACCAAGATCCTGCATGTCTTCC ATGGCCTTCTTCCTGGCTTCCTGGTGAAGATGAGTGGCGACCTGCTGGAGCTGGCCTTGAAGTTGCCC CATGTCGACTACATCGAGGAGGACTCCTCTGTCTTTGCCCAGagcatcccgtggaacctggagcggattacccctcca cggtaccgggcggatgaataccagccccccgacggaggcagcctggtggaggtgtatctcctagacaccagcatacagagtgaccaccgggaa atcgagggcagggtcatggtcaccgacttcgagaatgtgcccgaggaggacgggacccgcttccacagacaggccagcaagtgtgacagtcat ggcacccacctggcaggggtggtcagcggccgggatgccggcgtggccaagggtgccagcatgcgcagcctgcgcgtgctcaactgccaaggg aagggcacggttagcggcaccctcataggcctggagtttattcggaaaagccagctggtccagcctgtggggccactggtggtgctgctgcccct ggcgggtgggtacagccgcgtcctcaacgccgcctgccagcgcctggcgagggctggggtcgtgctggtcaccgctgccggcaacttccgggac gatgcctgcctctactccccagcctcagctcccgaggtcatcacagttggggccaccaatgcccaagaccagccggtgaccctggggactttggg gaccaactttggccgctgtgtggacctctttgccccaggggaggacatcattggtgcctccagcgactgcagcacctgctttgtgtcacagagtgg gacatcacaggctgctgcccacgtggctggcattgcagccatgatgctgctgccgagccggagctaccctggccgagttgaggcagagactg N425S AAT to AGT A443T GCC to ACC atccacttctctgccaaagatgtcatcagtgaggcctggttccctgaggaccagcgggtactgacccccaacctggtggccgccctgccccccag cacccatGGGGCAGGTTGGCAGCTGTTTTGCAGGACTGTATGGTCAGCACACTCGGGGCCTACACGGATGGCC I474V ATC to GTC ACAGCCGTCGCCCGCTGCGCCCCAGATGAGGAGCTGCTGAGCTGCTCCAGTTTCTCCAGGAGTGGGAAGCGG CGGGGCGAGCGCATGGAGGCCCAAGGGGGCAAGCTGGTCTGCCGGGCCCACAACGCTTTTGGGGGTGAGGG TGTCTACGCCATTGCCAGGTGCTGCCTGCTACCCCAGGCCAACTGCAGCGTCCACACAGCTCCACCAGCTGAG GCCAGCATGGGGACCCGTGTCCACTGCCACCAACAGGGCCACGTCCTCACAGGCTGCAGCTCCCACTGGGAG GTGGAGGACCTTGGCACCCACAAGCCGCCTGTGCTGAGGCCACGAGGTCAGCCCAACCAGTGCGTGGGCCAC AGGGAGGCCAGCATCCACGCTTCCTGCTGCCATGCCCCAGGTCTGGAATGCAAAGTCAAGGAGCATGGAA Q619P CAG to CCG E620G GAG to GGG TCCCGGCCCCTCAGGAGCAGGTGACCGTGGCCTGCGAGGAGGGCTGGACCCTGACTGGCTGCAGTGCCCTCC CTGGGACCTCCCACGTCCTGGGGGCCTACGCCGTAGACAACACGTGTGTAGTCAGGAGCCGGGACGTCAGCA E670G GAG to GGG CTACAGGCAGCACCAGCGAAGAGGCCGTGACAGCCGTTGCCATCTGCTGCCGGAGCCGGCACCTGGCGCAGG CCTCCCAGGAGCTCCAGTGAC h ATGGGCACCGTCAGCTCCAGGCGGTCCTGGTGGCCGCTGCCACTGCTGCTGCTGCTGCTGCTGCTCCTGGGTC 35 R46L CGT to CTT CCGCGGGCGCCCGTGCGCAGGAGGACGAGGACGGCGACTACGAGGAGCTGGTGCTAGCCTTGCGTTCCG A53V GCC to GTC AGGAGGACGGCCTGGCCGAAGCACCCGAGCACGGAACCACAGCCACCTTCCACCGCTGCGCCAAGGAT CCGTGGAGGTTGCCTGGCACCTACGTGGTGGTGCTGAAGGAGGAGACCCACCTCTCGCAGTCAGAGCG CACTGCCCGCCGCCTGCAGGCCCAGGCTGCCCGCCGGGGATACCTCACCAAGATCCTGCATGTCTTCC ATGGCCTTCTTCCTGGCTTCCTGGTGAAGATGAGTGGCGACCTGCTGGAGCTGGCCTTGAAGTTGCCC CATGTCGACTACATCGAGGAGGACTCCTCTGTCTTTGCCCAGagcatcccgtggaacctggagcggattacccctcca cggtaccgggcggatgaataccagccccccgacggaggcagcctggtggaggtgtatctcctagacaccagcatacagagtgaccaccgggaa atcgagggcagggtcatggtcaccgacttcgagaatgtgcccgaggaggacgggacccgcttccacagacaggccagcaagtgtgacagtcat ggcacccacctggcaggggtggtcagcggccgggatgccggcgtggccaagggtgccagcatgcgcagcctgcgcgtgctcaactgccaaggg aagggcacggttagcggcaccctcataggcctggagtttattcggaaaagccagctggtccagcctgtggggccactggtggtgctgctgcccct ggcgggtgggtacagccgcgtcctcaacgccgcctgccagcgcctggcgagggctggggtcgtgctggtcaccgctgccggcaacttccgggac gatgcctgcctctactccccagcctcagctcccgaggtcatcacagttggggccaccaatgcccaagaccagccggtgaccctggggactttggg gaccaactttggccgctgtgtggacctctttgccccaggggaggacatcattggtgcctccagcgactgcagcacctgctttgtgtcacagagtgg gacatcacaggctgctgcccacgtggctggcattgcagccatgatgctgctgccgagccggagctaccctggccgagttgaggcagagactg N425S AAT to AGT A443T GCC to ACC atccacttctctgccaaagatgtcatcaatgaggcctggttccctgaggaccagcgggtactgacccccaacctggtggccaccctgccccccag cacccatGGGGCAGGTTGGCAGCTGTTTTGCAGGACTGTATGGTCAGCACACTCGGGGCCTACACGGATGGCC I474V ATC to GTC ACAGCCATCGCCCGCTGCGCCCCAGATGAGGAGCTGCTGAGCTGCTCCAGTTTCTCCAGGAGTGGGAAGCGG CGGGGCGAGCGCATGGAGGCCCAAGGGGGCAAGCTGGTCTGCCGGGCCCACAACGCTTTTGGGGGTGAGGG TGTCTACGCCATTGCCAGGTGCTGCCTGCTACCCCAGGCCAACTGCAGCGTCCACACAGCTCCACCAGCTGAG GCCAGCATGGGGACCCGTGTCCACTGCCACCAACAGGGCCACGTCCTCACAGGCTGCAGCTCCCACTGGGAG GTGGAGGACCTTGGCACCCACAAGCCGCCTGTGCTGAGGCCACGAGGTCAGCCCAACCAGTGCGTGGGCCAC AGGGAGGCCAGCATCCACGCTTCCTGCTGCCATGCCCCAGGTCTGGAATGCAAAGTCAAGGAGCATGGAA Q619P CAG to CCG E620G GAG to GGG TCCCGGCCCCTCCGGAGCAGGTGACCGTGGCCTGCGAGGAGGGCTGGACCCTGACTGGCTGCAGTGCCCTCC CTGGGACCTCCCACGTCCTGGGGGCCTACGCCGTAGACAACACGTGTGTAGTCAGGAGCCGGGACGTCAGCA E670G GAG to GGG CTACAGGCAGCACCAGCGAAGAGGCCGTGACAGCCGTTGCCATCTGCTGCCGGAGCCGGCACCTGGCGCAGG CCTCCCAGGAGCTCCAGTGAC aj ATGGGCACCGTCAGCTCCAGGCGGTCCTGGTGGCCGCTGCCACTGCTGCTGCTGCTGCTGCTGCTCCTGGGTC 36 R46L CGT to CTT CCGCGGGCGCCCGTGCGCAGGAGGACGAGGACGGCGACTACGAGGAGCTGGTGCTAGCCTTGCTTTCCG A53V GCC to GTC AGGAGGACGGCCTGGCCGAAGCACCCGAGCACGGAACCACAGCCACCTTCCACCGCTGCGCCAAGGAT CCGTGGAGGTTGCCTGGCACCTACGTGGTGGTGCTGAAGGAGGAGACCCACCTCTCGCAGTCAGAGCG CACTGCCCGCCGCCTGCAGGCCCAGGCTGCCCGCCGGGGATACCTCACCAAGATCCTGCATGTCTTCC ATGGCCTTCTTCCTGGCTTCCTGGTGAAGATGAGTGGCGACCTGCTGGAGCTGGCCTTGAAGTTGCCC CATGTCGACTACATCGAGGAGGACTCCTCTGTCTTTGCCCAGagcatcccgtggaacctggagcggattacccctcca cggtaccgggcggatgaataccagccccccgacggaggcagcctggtggaggtgtatctcctagacaccagcatacagagtgaccaccgggaa atcgagggcagggtcatggtcaccgacttcgagaatgtgcccgaggaggacgggacccgcttccacagacaggccagcaagtgtgacagtcat ggcacccacctggcaggggtggtcagcggccgggatgccggcgtggccaagggtgccagcatgcgcagcctgcgcgtgctcaactgccaaggg aagggcacggttagcggcaccctcataggcctggagtttattcggaaaagccagctggtccagcctgtggggccactggtggtgctgctgcccct ggcgggtgggtacagccgcgtcctcaacgccgcctgccagcgcctggcgagggctggggtcgtgctggtcaccgctgccggcaacttccgggac gatgcctgcctctactccccagcctcagctcccgaggtcatcacagttggggccaccaatgcccaagaccagccggtgaccctggggactttggg gaccaactttggccgctgtgtggacctctttgccccaggggaggacatcattggtgcctccagcgactgcagcacctgctttgtgtcacagagtgg gacatcacaggctgctgcccacgtggctggcattgcagccatgatgctgctgccgagccggagctaccctggccgagttgaggcagagactg N425S AAT to AGT A443T GCC to ACC atccacttctctgccaaagatgtcatcaatgaggcctggttccctgaggaccagcgggtactgacccccaacctggtggccgccctgccccccag cacccatGGGGCAGGTTGGCAGCTGTTTTGCAGGACTGTATGGTCAGCACACTCGGGGCCTACACGGATGGCC I474V ATC to GTC ACAGCCGTCGCCCGCTGCGCCCCAGATGAGGAGCTGCTGAGCTGCTCCAGTTTCTCCAGGAGTGGGAAGCGG CGGGGCGAGCGCATGGAGGCCCAAGGGGGCAAGCTGGTCTGCCGGGCCCACAACGCTTTTGGGGGTGAGGG TGTCTACGCCATTGCCAGGTGCTGCCTGCTACCCCAGGCCAACTGCAGCGTCCACACAGCTCCACCAGCTGAG GCCAGCATGGGGACCCGTGTCCACTGCCACCAACAGGGCCACGTCCTCACAGGCTGCAGCTCCCACTGGGAG GTGGAGGACCTTGGCACCCACAAGCCGCCTGTGCTGAGGCCACGAGGTCAGCCCAACCAGTGCGTGGGCCAC AGGGAGGCCAGCATCCACGCTTCCTGCTGCCATGCCCCAGGTCTGGAATGCAAAGTCAAGGAGCATGGAA Q619P CAG to CCG E620G GAG to GGG TCCCGGCCCCTCAGGAGCAGGTGACCGTGGCCTGCGAGGAGGGCTGGACCCTGACTGGCTGCAGTGCCCTCC CTGGGACCTCCCACGTCCTGGGGGCCTACGCCGTAGACAACACGTGTGTAGTCAGGAGCCGGGACGTCAGCA E670G GAG to GGG CTACAGGCAGCACCAGCGAAGAGGCCGTGACAGCCGTTGCCATCTGCTGCCGGAGCCGGCACCTGGCGCAGG CCTCCCAGGAGCTCCAGTGAC q ATGGGCACCGTCAGCTCCAGGCGGTCCTGGTGGCCGCTGCCACTGCTGCTGCTGCTGCTGCTGCTCCTGGGTC 37 R46L CGT to CTT CCGCGGGCGCCCGTGCGCAGGAGGACGAGGACGGCGACTACGAGGAGCTGGTGCTAGCCTTGCGTTCCG A53V GCC to GTC AGGAGGACGGCCTGGTCGAAGCACCCGAGCACGGAACCACAGCCACCTTCCACCGCTGCGCCAAGGAT CCGTGGAGGTTGCCTGGCACCTACGTGGTGGTGCTGAAGGAGGAGACCCACCTCTCGCAGTCAGAGCG CACTGCCCGCCGCCTGCAGGCCCAGGCTGCCCGCCGGGGATACCTCACCAAGATCCTGCATGTCTTCC ATGGCCTTCTTCCTGGCTTCCTGGTGAAGATGAGTGGCGACCTGCTGGAGCTGGCCTTGAAGTTGCCC CATGTCGACTACATCGAGGAGGACTCCTCTGTCTTTGCCCAGagcatcccgtggaacctggagcggattacccctcca cggtaccgggcggatgaataccagccccccgacggaggcagcctggtggaggtgtatctcctagacaccagcatacagagtgaccaccgggaa atcgagggcagggtcatggtcaccgacttcgagaatgtgcccgaggaggacgggacccgcttccacagacaggccagcaagtgtgacagtcat ggcacccacctggcaggggtggtcagcggccgggatgccggcgtggccaagggtgccagcatgcgcagcctgcgcgtgctcaactgccaaggg aagggcacggttagcggcaccctcataggcctggagtttattcggaaaagccagctggtccagcctgtggggccactggtggtgctgctgcccct ggcgggtgggtacagccgcgtcctcaacgccgcctgccagcgcctggcgagggctggggtcgtgctggtcaccgctgccggcaacttccgggac gatgcctgcctctactccccagcctcagctcccgaggtcatcacagttggggccaccaatgcccaagaccagccggtgaccctggggactttggg gaccaactttggccgctgtgtggacctctttgccccaggggaggacatcattggtgcctccagcgactgcagcacctgctttgtgtcacagagtgg gacatcacaggctgctgcccacgtggctggcattgcagccatgatgctgctgccgagccggagctaccctggccgagttgaggcagagactg N425S AAT to AGT A443T GCC to ACC atccacttctctgccaaagatgtcatcaatgaggcctggttccctgaggaccagcgggtactgacccccaacctggtggccgccctgccccccag cacccatGGGGCAGGTTGGCAGCTGTTTTGCAGGACTGTATGGTCAGCACACTCGGGGCCTACACGGATGGCC I474V ATC to GTC ACAGCCATCGCCCGCTGCGCCCCAGATGAGGAGCTGCTGAGCTGCTCCAGTTTCTCCAGGAGTGGGAAGCGG CGGGGCGAGCGCATGGAGGCCCAAGGGGGCAAGCTGGTCTGCCGGGCCCACAACGCTTTTGGGGGTGAGGG TGTCTACGCCATTGCCAGGTGCTGCCTGCTACCCCAGGCCAACTGCAGCGTCCACACAGCTCCACCAGCTGAG GCCAGCATGGGGACCCGTGTCCACTGCCACCAACAGGGCCACGTCCTCACAGGCTGCAGCTCCCACTGGGAG GTGGAGGACCTTGGCACCCACAAGCCGCCTGTGCTGAGGCCACGAGGTCAGCCCAACCAGTGCGTGGGCCAC AGGGAGGCCAGCATCCACGCTTCCTGCTGCCATGCCCCAGGTCTGGAATGCAAAGTCAAGGAGCATGGAA Q619P CAG to CCG E620G GAG to GGG TCCCGGCCCCTCAGGAGCAGGTGACCGTGGCCTGCGAGGAGGGCTGGACCCTGACTGGCTGCAGTGCCCTCC CTGGGACCTCCCACGTCCTGGGGGCCTACGCCGTAGACAACACGTGTGTAGTCAGGAGCCGGGACGTCAGCA E670G GAG to GGG CTACAGGCAGCACCAGCGAAGGGGCCGTGACAGCCGTTGCCATCTGCTGCCGGAGCCGGCACCTGGCGCAGG CCTCCCAGGAGCTCCAGTGAC TABLE 7 Human VH3-23 Variant Alleles VH3-23 Cumulative allele haplotype frequency SNPs a (=VH3-23*04) 0.0983 rs56069819 d 0.0087 rs56069819 rs61750837 rs61752504 e 0.0046 rs56069819 rs1064090 rs1055799 j 0.0009 rs56069819 rs1055799 u 0.0005 rs56069819 rs1064091 s 0.0005 rs56069819 rs1064091 rs61752504 rs61750837 r 0.0005 rs56069819 rs1064090 TOTAL: 0.114 TABLE 8 Exemplary anti-PCSK9 antibodies and/or antibody fragments SEQ ID NOs comprising an anti-PCSK9 Patent or monoclonal antibody or fragment thereof patent Pblication Light chain complementary determining regions US20120020975 A1 (CDRL) SEQ ID NO: 5, 7, 9, 10, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, 46, 270, 271, 272, 273, 275, 277, 286, 287, 288, 297, 299, 301, 405, 407, 409, 411, 413, 415, 417, 421, 425, 429, 433, 437, 441, 445, 449, 453, 457, 461, 465, 469, 473, 477, 481, 485; Heavy chain complementary determining regions (CDRH) SEQ ID NO: 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 61, 62, 64, 65, 67, 69, 71, 72, 74, 76, 77, 78, 79, 80, 81, 83, 85, 87, 89, 91, 278, 289, 290, 291, 292, 298, 300, 302, 401, 404, 406, 408, 410, 412, 414, 416, 419, 423, 427, 431, 435, 439, 443, 447, 451, 455, 459, 463, 467, 471, 475, 479, 483; CDRL SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, US20120027765A1 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, 46, 405, 407, 409, 411, 413, 415, 417, 465; CDRH SEQ ID NO: 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 62, 64, 65, 67, 69, 71, 72, 74, 76, 77, 78, 79, 80, 81, 83, 85, 87, 89, 91, 404, 406, 408, 410, 412, 414, 416, 463; CDRL SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, U.S. Pat.","No.","17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 8,168,762B2 33, 35, 36, 37, 38, 39, 40, 42, 44, 46, 405, 407, 409, 411, 413, 415, 417, 465; CDRH SEQ ID NO: 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 62, 64, 65, 67, 69, 71, 72, 74, 76, 77, 78, 79, 80, 81, 83, 85, 87, 89, 91, 404, 406, 408, 410, 412, 414, 416, 463; CDRL SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, US20120020976A1 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, 46, 222, 229, 238, 405, 407, 409, 411, 413, 415, 417; CDRH SEQ ID NO: 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 62, 64, 65, 67, 69, 71, 72, 74, 76, 77, 78, 79, 80, 81, 83, 85, 87, 89, 91, 247, 256, 265, 404, 406, 408, 410, 412, 414, 416; CDRL SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, US20130085265A1 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, 46, 405, 407, 409, 411, 413, 415, 417, 461, 465, 485; CDRH SEQ ID NO: 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 62, 64, 65, 67, 69, 71, 72, 74, 76, 77, 78, 79, 80, 81, 83, 85, 87, 89, 91, 404, 406, 408, 410, 412, 414, 416, 459, 463, 483; CDRL SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, US20130079501A1 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, 46, 405, 407, 409, 411, 413, 415, 417, 461, 465, 485; CDRH SEQ ID NO: 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 62, 64, 65, 67, 69, 71, 72, 74, 76, 77, 78, 79, 80, 81, 83, 85, 87, 89, 91, 404, 406, 408, 410, 412, 414, 416, 459, 463, 483; CDRL SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, US20120213797A1 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, 46, 405, 407, 409, 411, 413, 415, 417, 158, 162, 395, 473, 477; CDRH SEQ ID NO: 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 62, 64, 65, 67, 69, 71, 72, 74, 76, 77, 78, 79, 80, 81, 83, 85, 87, 89, 91, 404, 406, 408, 410, 412, 414, 416, 180, 175, 308, 368, 471, 475; CDRL SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, US20120251544A1 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, 46, 405, 407, 409, 411, 413, 415, 417; CDRH SEQ ID NO: 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 62, 64, 65, 67, 69, 71, 72, 74, 76, 77, 78, 79, 80, 81, 83, 85, 87, 89, 91, 404, 406, 408, 410, 412, 414, 416; CDRL SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, US20130052201A1 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, 46, 405, 407, 409, 411, 413, 415, 417, 461, 465, 485; CDRH SEQ ID NO: 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 62, 64, 65, 67, 69, 71, 72, 74, 76, 77, 78, 79, 80, 81, 83, 85, 87, 89, 91, 404, 406, 408, 410, 412, 414, 416, 459, 463, 483; CDRL SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, US20130058944A1 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, 46, 405, 407, 409, 411, 413, 415, 417, 461, 465, 485; CDRH SEQ ID NO: 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 62, 64, 65, 67, 69, 71, 72, 74, 76, 77, 78, 79, 80, 81, 83, 85, 87, 89, 91, 404, 406, 408, 410, 412, 414, 416, 459, 463, 483; CDRL SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, US20130079502A1 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, 46, 405, 407, 409, 411, 413, 415, 417; CDRH SEQ ID NO: 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 62, 64, 65, 67, 69, 71, 72, 74, 76, 77, 78, 79, 80, 81, 83, 85, 87, 89, 91, 404, 406, 408, 410, 412, 414, 416; CDRL SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, US20130245235A1 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, 46, 405, 407, 409, 411, 413, 415, 417; CDRH SEQ ID NO: 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 62, 64, 65, 67, 69, 71, 72, 74, 76, 77, 78, 79, 80, 81, 83, 85, 87, 89, 91, 404, 406, 408, 410, 412, 414, 416; TABLE 9 Human variable & constant variants distributed over several human ethnic populations - useful for ligand tailoring Nucleotide Hom Human Variation2 Freq7 Gene Example Amino Acid (NCBI dbSNP Variant (Het + Segment Human Position & reference Nucleotide Human No.","Het Hom Cum Type Allele1 Variation number)3 Position Populations4 Individs5 Freq6 freq8) Freq9 IGHG1 IGHG1*01 204D GAT 14:106208086 A 153 0.400 0.096 0.296 (CH3 (forward strand) (European (0.496) variation) ancestry) IGHG1*03 204E GAG 14:106208086 A 366 0.400 0.504 0.704 (CH3 (rs1045853) (forward strand) (European (0.904) variation) ancestry IGHG1*01 206L CTG 14:106208082 A 0.358 0.104 0.283 (CH3 (forward strand) (European (0.462) variation) ancestry) IGHG1*03 206M ATG 14:106208082 A 0.358 0.538 0.717 (CH3 (rs11621259) (forward strand) (European (0.896) variation) ancestry) IGHG2 IGHG2*01 72P CCC 14:106110914 B 0.336 0.540 0.708 (CH1 (forward strand) (0.876) variation) IGHG2*02 72T ACC 14:106110914 B 0.336 0.124 0.292 (CH1 (rs11627594) (forward strand) variation) IGHG2*01 75N AAC 14:106110904 A 0.007 0.993 0.997 (CH1 (forward strand) variation) IGHG2*04 75S AGC 14:106110904 A 0.007 0.004 (CH1 (rs201590297) (forward strand) variation) IGHG2*01 76F TTC (CH1 variation) IGHG2*04 76L TTG (CH1 variation) IGHG2*01 161V GTG 14:10611013 B 0.342 0.539 0.711 (CH2 (forward strand) (0.881) variation) IGHG2*02 161M ATG 14:10611013 B 0.342 0.118 0.289 (CH2 (rs8009156) (forward strand) (0.46) variation) IGHG2*01 257A GCC 14:106109752 C 0.199 0.493 0.592 (CH3 (forward strand) (0.692) variation) D 0.007 0.992 0.995 (0.999) IGHG2*06 257S TCC 14:106109752 C 0.199 0.308 0.408 (CH3 (rs4983499) (forward strand) (0.507) variation) D 0.007 0.002 0.005 (0.009) Table Footnotes: 1IMGT notation (ww.imgt.org); refer to figures for other alleles comprising this variation.","2SNP Underlined in Codon.","3NCBI dbSNP Build 138 released on Apr.","25, 2013.4Human population used for representative variant frequency analysis.","Populations A This population included 662 participants of European descent from the ClinSeq project, all of whom had undergone whole-exome sequencing using Agilent's 38Mb or 50Mb capture kit.","B 1000 Genomes database.","C ESP6500: African_American.","D ESP6500: European_American.","5Number of individuals in representative population found to have the allele.","6Heterozygous human genotype frequency, ie, cumulative frequency of all genotypes having one occurrence of the variant allele and one occurrence of another allele (heterozygous state), eg, ac genotype in the population.","7Homozygous human genotype frequency, ie, cumulative frequency of two occurrences of the variant allele (homozygous state), eg, cc genotype in the population.","8Total human genotype frequency, ie, total of heterozygous plus homozygous human genotype frequencies.","9Cumulative human allele frequency of all occurrences of the variant allele in the population.","TABLE 10 FURTHER SEQUENCES SEQ ID Human NO: Allele Nucleotide/Amino Acid Sequence HEAVY CHAIN ALLELES 41 IGHG1*01 gcctccaccaagggcccatcggtcttccccctggcaccctcctccaaga (CH1 + Hinge + gcacctctggg CH2 + CH3 + CH- ggcacagcggccctgggctgcctggtcaaggactacttccccgaaccgg S) tgacggtgtcg tggaactcaggcgccctgaccagcggcgtgcacaccttcccggctgtcc tacagtcctca ggactctactccctcagcagcgtggtgaccgtgccctccagcagcttgg gcacccagacc tacatctgcaacgtgaatcacaagcccagcaacaccaaggtggacaaga aagttgagccc aaatcttgtgacaaaactcacacatgcccaccgtgcccagcacctgaac tcctgggggga ccgtcagtcttcctcttccccccaaaacccaaggacaccctcatgatct cccggacccct gaggtcacatgcgtggtggtggacgtgagccacgaagaccctgaggtca agttcaactgg tacgtggacggcgtggaggtgcataatgccaagacaaagccgcgggagg agcagtacaac agcacgtaccgggtggtcagcgtcctcaccgtcctgcaccaggactggc tgaatggcaag gagtacaagtgcaaggtctccaacaaagccctcccagcccccatcgaga aaaccatctcc aaagccaaagggcagccccgagaaccacaggtgtacaccctgcccccat cccgggatgag ctgaccaagaaccaggtcagcctgacctgcctggtcaaaggcttctatc ccagcgacatc gccgtggagtgggagagcaatgggcagccggagaacaactacaagacca cgcctcccgtg ctggactccgacggctccttcttcctctacagcaagctcaccgtggaca agagcaggtgg cagcaggggaacgtcttctcatgctccgtgatgcatgaggctctgcaca accactacacg cagaagagcctctccctgtctccgggtaaa 42 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSG VHTFPAVLQSS GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTC PPCPAPELLGG PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHN AKTKPREEQYN STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP QVYTLPPSRDE LTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTIPPVLDSDGSFFL YSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPGK D = position 204 L = position 206 43 IGHG2*01 gcctccaccaagggcccatcggtcttccccctggcgccctgctccagga (CH1 + Hinge + gcacctccgag CH2 + CH3 + CH- agcacagccgccctgggctgcctggtcaaggactacttccccgaaccgg S) tgacggtgtcg tggaactcaggcgctctgaccagcggcgtgcacaccttcccagctgtcc tacagtcctca ggactctactccctcagcagcgtggtgaccgtgccctccagcaacttcg gcacccagacc tacacctgcaacgtagatcacaagcccagcaacaccaaggtggacaaga cagttgagcgc aaatgttgtgtcgagtgcccaccgtgcccagcaccacctgtggcaggac cgtcagtcttc ctcttccccccaaaacccaaggacaccctcatgatctcccggacccctg aggtcacgtgc gtggtggtggacgtgagccacgaagaccccgaggtccagttcaactggt acgtggacggc gtggaggtgcataatgccaagacaaagccacgggaggagcagttcaaca gcacgttccgt gtggtcagcgtcctcaccgttgtgcaccaggactggctgaacggcaagg agtacaagtgc aaggtctccaacaaaggcctcccagcccccatcgagaaaaccatctcca aaaccaaaggg cagccccgagaaccacaggtgtacaccctgcccccatcccgggaggaga tgaccaagaac caggtcagcctgacctgcctggtcaaaggcttctaccccagcgacatcg ccgtggagtgg gagagcaatgggcagccggagaacaactacaagaccacacctcccatgc tggactccgac ggctccttcttcctctacagcaagctcaccgtggacaagagcaggtggc agcaggggaac gtcttctcatgctccgtgatgcatgaggctctgcacaaccactacacgc agaagagcctc tccctgtctccgggtaaa 44 ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSG VHTFPAVLQSS GLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPC PAPPVAGPSVF LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTK PREEQFNSTFR VVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYT LPPSREEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKL TVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGK P = position 72 N = position 75 F = position 76 V = position 161 A = position 257 45 IGHV1-18*01 caggttcagctggtgcagtctggagctgaggtgaagaagcctggggcct cagtgaaggtc tcctgcaaggcttctggttacacctttaccagctatggtatcagctggg tgcgacaggcc cctggacaagggcttgagtggatgggatggatcagcgcttacaatggta acacaaactat gcacagaagctccagggcagagtcaccatgaccacagacacatccacga gcacagcctac atggagctgaggagcctgagatctgacgacacggccgtgtattactgtg cgagaga 46 QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAP GQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDD TAVYYCAR 47 IGHV1-46*01 caggtgcagctggtgcagtctggggctgaggtgaagaagcctggggcct cagtgaaggtt tcctgcaaggcatctggatacaccttcaccagctactatatgcactggg tgcgacaggcc cctggacaagggcttgagtggatgggaataatcaaccctagtggtggta gcacaagctac gcacagaagttccagggcagagtcaccatgaccagggacacgtccacga gcacagtctac atggagctgagcagcctgagatctgaggacacggccgtgtattactgtg cgagaga 48 QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAP GQGLEWMGIINPSGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSED TAVYYCAR LIGHT CHAIN ALLELES 49 IGKC*01 cgaactgtggctgcaccatctgtcttcatcttcccgccatctgatgagc agttgaaatct ggaactgcctctgttgtgtgcctgctgaataacttctatcccagagagg ccaaagtacag tggaaggtggataacgccctccaatcgggtaactcccaggagagtgtca cagagcaggac agcaaggacagcacctacagcctcagcagcaccctgacgctgagcaaag cagactacgag aaacacaaagtctacgcctgcgaagtcacccatcagggcctgagctcgc ccgtcacaaag agcttcaacaggggagagtgt 50 RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQD SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC V = position 84 C = position 87 51 IGLC2*01 ggtcagcccaaggctgccccctcggtcactctgttcccgccctcctctg aggagcttcaa gccaacaaggccacactggtgtgtctcataagtgacttctacccgggag ccgtgacagtg gcttggaaagcagatagcagccccgtcaaggcgggagtggagaccacca caccctccaaa caaagcaacaacaagtacgcggccagcagctatctgagcctgacgcctg agcagtggaag tcccacagaagctacagctgccaggtcacgcatgaagggagcaccgtgg agaagacagtg gcccctacagaatgttca 52 GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPV KAGVETTTPSK QSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 53 IGKV4-1*01 atggtgttgcagacccaggtcttcatttctctgttgctctggatctctg gtgcctacggg gacatcgtgatgacccagtctccagactccctggctgtgtctctgggcg agagggccacc atcaactgcaagtccagccagagtgttttatacagctccaacaataaga actacttagct tggtaccagcagaaaccaggacagcctcctaagctgctcatttactggg catctacccgg gaatccggggtccctgaccgattcagtggcagcgggtctgggacagatt tcactctcacc atcagcagcctgcaggctgaagatgtggcagtttattactgtcagcaat attatagtact cctcc 54 DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKNYLA WYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDV AVYYCQQYYST P 55 IGKV1-13*02 atggacatgagggtccccgctcagctcctggggcttctgctgctctggc tcccagcaggt gccagatgtgccatccagttgacccagtctccatcctccctgtctgcat ctgtaggagac agagtcaccatcacttgccgggcaagtcagggcattagcagtgctttag cctggtatcag cagaaaccagggaaagctcctaagctcctgatctatgatgcctccagtt tggaaagtggg gtcccatcaaggttcagcggcagtggatctgggacagatttcactctca ccatcagcagc ctgcagcctgaagattttgcaacttattactgtcaacagtttaatagtt accctcagtgc cagatgtgccatccagttgacccagtctccatcctccctgtctgcatct gtaggagacag agtcaccatcacttgccgggcaagtcagggcattagcagtgctttagcc tggtatcagca gaaaccagggaaagctcctaagctcctgatctatgatgcctccagtttg gaaagtggggt cccatcaaggttcagcggcagtggatctgggacagatttcactctcacc atcagcagcct gcagcctgaagattttgcaacttattactgtcaacagtttaatagttac cctca 57 IGKJ2*01 tgtacacttttggccaggggaccaagctggagatcaaac 58 YTFGQGTKLEIK 59 IGLJ2*01 tgtggtattcggcggagggaccaagctgaccgtcctag 60 VVFGGGTKLTVL 61 An IGHG1*01 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSG Heavy Chain VHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKV Constant EPKSCDKTHTCPPCPAPELLGGPS Region VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAK TKPREEQYNST YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV YTLPPSRDELT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 62 An IGKC*01 RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS Kappa Light GNSQESVIEQDSKDSTYSLSSILTLSKADYEKHKVYACEVTHQGLSSPV Chain TKSFNRGEC Constant Region 63 An IGHG2*01 ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSG Heavy Chain VHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTV Constant ERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSH Region EDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGK EYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 64 An IGLC2*01 QPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVK Lambda AGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKT Light Chain VAPTECS Constant Region 65 An IGHG2*01 ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSG Heavy Chain VHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTV Constant ERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSH Region EDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGK EYKCKVSNKGLPSSIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 66 An IGKC*01 RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS Kappa Light GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV Chain TKSFNRGEC Constant Region"]],"string":"[\n [\n \"PRECISION MEDICINE FOR CHOLESTEROL TREATMENT\",\n \"The invention relates to human targets of interest (TOI), anti-TOI ligands, kits compositions and method.\"\n ],\n [\n \"1.A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, wherein the method comprises administering an antibody or antibody fragment to the human, wherein (i) the antibody or fragment specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) encoded by the nucleotide sequence of SEQ ID NO: 30, SEQ ID NO: 31 or SEQ ID NO: 37 and the antibody or fragment comprises heavy chain and light chain variable domains of alirocumab; and (ii) said human comprises said nucleotide sequence encoding PCSK9.2.The method of claim 1, wherein the human is or has been further determined to be substantially resistant to statin treatment.\",\n \"3.The method of claim 1, wherein the human is receiving or has received statin treatment or has reduced responsiveness to statin treatment.\",\n \"4.The method of claim 1, wherein said antibody or antibody fragment is administered to the human separately or simultaneously with statin treatment.\",\n \"5.The method of claim 1, wherein said human is indicated as homozygous for the nucleotide sequence SEQ ID NO: 30, SEQ ID NO: 31 or SEQ ID NO: 37.6.The method of claim 1, wherein said human has been diagnosed with coronary heart disease or atherosclerosis.\",\n \"7.The method of claim 1, wherein the method treats or reduces the risk in said human of coronary heart disease or atherosclerosis.\",\n \"8.The method of claim 1, wherein the antibody or fragment is administered to the human by intravenous or subcutaneous administration and/or is comprised in an injectable preparation.\",\n \"9.The method of claim 1, wherein the antibody has human glycosylation produced by a CHO cell.\",\n \"10.The method of claim 1, wherein the antibody is alirocumab.\"\n ],\n [\n \" BACKGROUND It is recognized that individual humans differ in their sequence and recently several individuals have had their genomes sequenced, for instance James Watson and Craig Venter.\",\n \"Comparison of the genome sequence of individuals has revealed differences in their sequences in both coding and non-coding parts of the genome.\",\n \"Some of these variations in humans are significant and contribute to phenotypic differences between individuals.\",\n \"In extreme cases these will result in genetic disease.\",\n \"The 1000 Genomes Project has the objective of cataloguing sequences in the human genome, involving sequencing the genomes of a very large sampling of individuals from diverse art-recognized human ethnic populations.\"\n ],\n [\n \" SUMMARY Through the application of human genetic variation analysis and rationally-designed sequence selection the present invention provides for improved human patient diagnosis and therapy.\",\n \"Importantly, the invention enables tailored medicines that address individual human patient genotypes or phenotypes.\",\n \"The inventor's analysis of large numbers of naturally-occurring genomic human TOI sequences reveals that there is significant variation across diverse human populations and provides for the ability for correlation between individual human patients and tailored medical and diagnostic approaches addressing the target.\",\n \"The technical applications of these findings, as per the present invention, thus contribute to better treatment, prophylaxis and diagnosis in humans and provides for patient benefit by enabling personalized medicines and therapies.\",\n \"This provides advantages of better prescribing, less wastage of medications and improved chances of drug efficacy and better diagnosis in patients.\",\n \"Furthermore, the inventor surprisingly realised that some rarer natural forms, although present in humans at much lower frequencies than the common form, nevertheless are represented in multiple and ethnically-diverse human populations and usually with many human examples per represented ethnic population.\",\n \"Thus, the inventor realised that targeting such rarer forms would provide for effective treatment, prophylaxis or diagnosis across many human ethnic populations, thereby extending the utility of the present invention and better serving patients in those populations.\",\n \"With this, the inventor realised that there is significant industrial and medical application for the invention in terms of guiding the choice of an anti-TOI ligand for administration to human patients for therapy and/or prophylaxis of TOI-mediated or associated diseases and conditions.\",\n \"In this way, the patient receives drugs and ligands that are tailored to their needs—as determined by the patient's genetic or phenotypic makeup.\",\n \"Hand-in-hand with this, the invention provides for the genotyping and/or phenotyping of patients in connection with such treatment, thereby allowing a proper match of drug to patient.\",\n \"This increases the chances of medical efficacy, reduces the likelihood of inferior treatment using drugs or ligands that are not matched to the patient (eg, poor efficacy and/or side-effects) and avoids pharmaceutical mis-prescription and waste.\",\n \"To this end, the invention provides:— In a First Configuration A method of treating or preventing a disease or condition in a human, wherein the disease or condition is mediated by a Target of Interest (TOI), wherein the TOI is present in humans as different polymorphic variants, the method comprising a.\",\n \"Administering to the human an anti-TOI ligand to target a TOI variant in the human and treat or prevent said disease or condition, wherein the TOI in said human is encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or wherein the TOI in said human is encoded by a nucleotide sequence having a total human genotype frequency of less than 50%; wherein b.\",\n \"Before step (a) said human has been or is genotyped as positive for said nucleotide sequence or phenotyped as positive for said TOI variant.\",\n \"In a Second Configuration A method of treating or preventing a disease or condition in a human, wherein the disease or condition is mediated by a Target of Interest (TOI), wherein the TOI is present in humans as different polymorphic variants, the method comprising a.\",\n \"Administering to the human an anti-TOI ligand to target a TOI variant in the human and treat or prevent said disease or condition, wherein the TOI in said human is encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or wherein the TOI in said human is encoded by a nucleotide sequence having a total human genotype frequency of less than 50%; wherein b. before step (a) the ligand has been or is determined as capable of binding to said TOI variant.\",\n \"In a Third Configuration A method of treating or preventing a disease or condition in a human, wherein the disease or condition is mediated by a Target of Interest (TOI), wherein the TOI is present in humans as different polymorphic variants, the method comprising a.\",\n \"Administering to the human an anti-TOI ligand to target a TOI variant in the human and treat or prevent said disease or condition, wherein the TOI in said human is a variant encoded by a nucleotide sequence having a cumulative human allele frequency of more than 50% and/or having a total human genotype frequency of more than 50%; wherein b.\",\n \"Before step (a) said human has been or is genotyped as negative for a variant nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%; or phenotyped as negative for a TOI variant encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.\",\n \"In a Fourth Configuration An anti-human TOI ligand for use in a method of treating and/or preventing a TOI-mediated disease or condition in a human, wherein the TOI is present in humans as different polymorphic variants and wherein the genome of said human comprises a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, the method comprising administering the ligand to the human.\",\n \"In a Fifth Configuration A ligand that binds a human TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, for use in a method comprising the step of using the ligand to target said TOI in a human to treat and/or prevent a disease or condition mediated by TOI, the method comprising administering the ligand to the human.\",\n \"In a Sixth Configuration A pharmaceutical composition or kit for treating or preventing a condition or disease mediated by a TOI.\",\n \"In a Seventh Configuration A method of producing an anti-human TOI antibody binding site, the method comprising obtaining a plurality of anti-TOI antibody binding sites, screening the antibody binding sites for binding to a TOI comprising an amino acid sequence encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, or to a peptide thereof that comprises an amino acid variation from the corresponding sequence encoded by the TOI-encoding nucleotide sequence having the highest cumulative human allele frequency and/or the highest total human genotype frequency, and isolating an antibody binding site that binds in the screening step.\",\n \"In a Eighth Configuration A method of producing an anti-human TOI antibody, the method comprising immunising a non-human vertebrate (eg, a mouse or a rat) with a TOI comprising an amino acid sequence encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, or to a peptide thereof that comprises an amino acid variation from the corresponding sequence encoded by the TOI-encoding nucleotide sequence having the highest cumulative human allele frequency and/or the highest total human genotype frequency, and isolating an antibody that binds a TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, and optionally producing a TOI-binding fragment or derivative of the isolated antibody.\",\n \"In a Ninth Configuration A kit for TOI genotyping a human, wherein the kit comprises a nucleic acid comprising a nucleotide sequence that specifically hybridises to a TOI nucleotide sequence selected having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50% or an RNA transcript thereof; and/or the nucleic acid comprises a nucleotide sequence that comprises at least 10 contiguous nucleotides of a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50% or is an antisense sequence thereof.\",\n \"In a Tenth Configuration Use of an anti-TOI ligand that binds a human TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, in the manufacture of a medicament for treating and/or preventing a TOI-mediated disease or condition in a human whose genome comprises a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.\",\n \"In a Eleventh Configuration Use of an anti-TOI ligand that binds a human TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, in the manufacture of a medicament for targeting said TOI in a human to treat and/or prevent a disease or condition mediated by TOI.\",\n \"In a Twelfth Configuration A method of targeting a TOI for treating and/or preventing a TOI-mediated disease or condition in a human, the method comprising administering an anti-TOI ligand to a human comprising a TOI nucleotide sequence selected having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, whereby a TOI encoded by said nucleotide sequence is targeted.\",\n \"In a Thirteenth Configuration A method of TOI genotyping a nucleic acid sample of a human, the method comprising identifying in the sample the presence of a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.\",\n \"In a Fourteenth Configuration A method of TOI typing a protein sample of a human, the method comprising identifying in the sample the presence of a TOI amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.\",\n \"In an example, the TOI is a human TOI selected from the group consisting of PCSK9, VEGF-A and IL6 receptor.\",\n \"A Fifteenth Configuration provides a ligand, method, use, kit or composition of the invention, wherein (i) the ligand (eg, antibody or fragment) comprises (a) a variable domain that is encoded by a human V region nucleotide sequence, wherein the V nucleotide sequence is derived from recombination of human VH, D and JH gene segments or human VL and JL gene segments; or (b) a constant region domain encoded by a C region gene segment; Wherein a first gene segment of said gene segments of (a), or said C region gene segment of (b) comprises a first single nucleotide polymorphism (SNP) encoding a first amino acid polymorphism; and (ii) the genome of said human comprises said first SNP or wherein said human expresses (a′) an antibody variable domain comprising said first amino acid polymorphism or (b′) an antibody constant domain comprising said first amino acid polymorphism.\",\n \"A Sixteenth Configuration provides the ligand, method, use, kit or composition of the invention, wherein the ligand comprises or consists of an antibody or fragment that comprises a human antibody variable domain derived from the recombination of a human V gene segment and a human J gene segment (and optionally a human D gene segment when the variable domains are VH domains); and wherein the genome of the human comprises said human V gene segment and/or the human expresses antibodies comprising antibody variable domains derived from the recombination of said human V gene segment and a human J gene segment (and optionally a human D gene segment).\",\n \"A Sixteenth Configuration provides the ligand, method, use, kit or composition of the invention, wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused human PCSK9 receptor) comprises a human heavy chain constant domain encoded by a first constant region nucleotide sequence; and wherein the genome of the human comprises a heavy chain constant region nucleotide sequence that is identical to said first constant region nucleotide sequence and/or the human expresses antibodies comprising said human constant domain.\",\n \"A Seventeenth Configuration provides the ligand, method, use, kit or composition of the invention, wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused TOI receptor) comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 or a Leu corresponding to position 206 of SEQ ID NO: 42 and wherein the genome of the human comprises a gamma-1 heavy chain constant region nucleotide sequence that encodes such an Asp or Leu or the human expresses antibodies comprising human gamma-1 constant regions comprising such an Asp or Leu.\",\n \"A Eighteenth Configuration provides the ligand, method, use, kit or composition of the invention, wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused TOI receptor) comprises a human gamma-2 heavy chain constant region that comprises an amino acid selected from the group consisting of a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44, a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44; and wherein the genome of the human comprises a gamma-2 heavy chain constant region nucleotide sequence that encodes such a selected amino acid or the human expresses antibodies comprising human gamma-2 constant regions comprising such a selected amino acid.\",\n \"A Nineteenth Configuration provides the ligand, method, use, kit or composition of the invention, wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused TOI receptor) comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 or a Cys corresponding to position 87 of SEQ ID NO: 50; and wherein the genome of the human comprises a kappa light chain constant region nucleotide sequence that encodes such a Val or Cys or the human expresses antibodies comprising human kappa light chain constant regions comprising such a Val or Cys.\",\n \"A Twentieth Configuration provides the ligand, method, use, kit or composition of the invention, wherein the ligand comprises or consists of an antibody or fragment, wherein the antibody or fragment comprises a VH domain that is derived from the recombination of a human VH gene segment, a human D gene segment and a human JH gene segment, wherein the VH gene segment is selected from the group consisting of (i) IGHV1-18*01 and the genome of the human comprises a human IGHV1-18*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGHV1-18*01; or (ii) IGVH1-46*01 and the genome of the human comprises a human IGHV1-46*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGHV1-46*01.A Twenty-First Configuration provides the ligand, method, use, kit or composition of the invention, wherein the ligand comprises or consists of an antibody or fragment, wherein the antibody or fragment comprises a VL domain that is derived from the recombination of a human VL gene segment and a human JL gene segment, wherein the VL gene segment is selected from the group consisting of (i) IGKV4-1*01 and the genome of the human comprises a human IGKV4-1*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGKV4-1*01; (ii) IGLV2-14*01 and the genome of the human comprises a human IGLV2-14*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGLV2-14*01; or (iii) IGKV1-13*02 and the genome of the human comprises a human IGKV1-13*02 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGKV1-13*02.\"\n ],\n [\n \"CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of co-pending U.S. application Ser.\",\n \"No.\",\n \"14/331,730 filed Jul.\",\n \"15, 2014, the entire content of which is incorporated by reference.\",\n \"SEQUENCE LISTING The instant application contains a Sequence Listing which has been submitted electronically in ASCII format and is hereby incorporated by reference in its entirety.\",\n \"Said ASCII copy, created on Jul.\",\n \"14, 2014, is named 069496-080095_SL.txt and is 222,931 bytes in size.\",\n \"TECHNICAL FIELD The technology described herein relates to ligands, e.g., antibodies for the treatment of disease.\",\n \"BACKGROUND It is recognized that individual humans differ in their sequence and recently several individuals have had their genomes sequenced, for instance James Watson and Craig Venter.\",\n \"Comparison of the genome sequence of individuals has revealed differences in their sequences in both coding and non-coding parts of the genome.\",\n \"Some of these variations in humans are significant and contribute to phenotypic differences between individuals.\",\n \"In extreme cases these will result in genetic disease.\",\n \"The 1000 Genomes Project has the objective of cataloguing sequences in the human genome, involving sequencing the genomes of a very large sampling of individuals from diverse art-recognized human ethnic populations.\",\n \"SUMMARY Through the application of human genetic variation analysis and rationally-designed sequence selection the present invention provides for improved human patient diagnosis and therapy.\",\n \"Importantly, the invention enables tailored medicines that address individual human patient genotypes or phenotypes.\",\n \"The inventor's analysis of large numbers of naturally-occurring genomic human TOI sequences reveals that there is significant variation across diverse human populations and provides for the ability for correlation between individual human patients and tailored medical and diagnostic approaches addressing the target.\",\n \"The technical applications of these findings, as per the present invention, thus contribute to better treatment, prophylaxis and diagnosis in humans and provides for patient benefit by enabling personalized medicines and therapies.\",\n \"This provides advantages of better prescribing, less wastage of medications and improved chances of drug efficacy and better diagnosis in patients.\",\n \"Furthermore, the inventor surprisingly realised that some rarer natural forms, although present in humans at much lower frequencies than the common form, nevertheless are represented in multiple and ethnically-diverse human populations and usually with many human examples per represented ethnic population.\",\n \"Thus, the inventor realised that targeting such rarer forms would provide for effective treatment, prophylaxis or diagnosis across many human ethnic populations, thereby extending the utility of the present invention and better serving patients in those populations.\",\n \"With this, the inventor realised that there is significant industrial and medical application for the invention in terms of guiding the choice of an anti-TOI ligand for administration to human patients for therapy and/or prophylaxis of TOI-mediated or associated diseases and conditions.\",\n \"In this way, the patient receives drugs and ligands that are tailored to their needs—as determined by the patient's genetic or phenotypic makeup.\",\n \"Hand-in-hand with this, the invention provides for the genotyping and/or phenotyping of patients in connection with such treatment, thereby allowing a proper match of drug to patient.\",\n \"This increases the chances of medical efficacy, reduces the likelihood of inferior treatment using drugs or ligands that are not matched to the patient (eg, poor efficacy and/or side-effects) and avoids pharmaceutical mis-prescription and waste.\",\n \"To this end, the invention provides:— In a First Configuration A method of treating or preventing a disease or condition in a human, wherein the disease or condition is mediated by a Target of Interest (TOI), wherein the TOI is present in humans as different polymorphic variants, the method comprising a.\",\n \"Administering to the human an anti-TOI ligand to target a TOI variant in the human and treat or prevent said disease or condition, wherein the TOI in said human is encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or wherein the TOI in said human is encoded by a nucleotide sequence having a total human genotype frequency of less than 50%; wherein b.\",\n \"Before step (a) said human has been or is genotyped as positive for said nucleotide sequence or phenotyped as positive for said TOI variant.\",\n \"In a Second Configuration A method of treating or preventing a disease or condition in a human, wherein the disease or condition is mediated by a Target of Interest (TOI), wherein the TOI is present in humans as different polymorphic variants, the method comprising a.\",\n \"Administering to the human an anti-TOI ligand to target a TOI variant in the human and treat or prevent said disease or condition, wherein the TOI in said human is encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or wherein the TOI in said human is encoded by a nucleotide sequence having a total human genotype frequency of less than 50%; wherein b. before step (a) the ligand has been or is determined as capable of binding to said TOI variant.\",\n \"In a Third Configuration A method of treating or preventing a disease or condition in a human, wherein the disease or condition is mediated by a Target of Interest (TOI), wherein the TOI is present in humans as different polymorphic variants, the method comprising a.\",\n \"Administering to the human an anti-TOI ligand to target a TOI variant in the human and treat or prevent said disease or condition, wherein the TOI in said human is a variant encoded by a nucleotide sequence having a cumulative human allele frequency of more than 50% and/or having a total human genotype frequency of more than 50%; wherein b.\",\n \"Before step (a) said human has been or is genotyped as negative for a variant nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%; or phenotyped as negative for a TOI variant encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.\",\n \"In a Fourth Configuration An anti-human TOI ligand for use in a method of treating and/or preventing a TOI-mediated disease or condition in a human, wherein the TOI is present in humans as different polymorphic variants and wherein the genome of said human comprises a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, the method comprising administering the ligand to the human.\",\n \"In a Fifth Configuration A ligand that binds a human TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, for use in a method comprising the step of using the ligand to target said TOI in a human to treat and/or prevent a disease or condition mediated by TOI, the method comprising administering the ligand to the human.\",\n \"In a Sixth Configuration A pharmaceutical composition or kit for treating or preventing a condition or disease mediated by a TOI.\",\n \"In a Seventh Configuration A method of producing an anti-human TOI antibody binding site, the method comprising obtaining a plurality of anti-TOI antibody binding sites, screening the antibody binding sites for binding to a TOI comprising an amino acid sequence encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, or to a peptide thereof that comprises an amino acid variation from the corresponding sequence encoded by the TOI-encoding nucleotide sequence having the highest cumulative human allele frequency and/or the highest total human genotype frequency, and isolating an antibody binding site that binds in the screening step.\",\n \"In a Eighth Configuration A method of producing an anti-human TOI antibody, the method comprising immunising a non-human vertebrate (eg, a mouse or a rat) with a TOI comprising an amino acid sequence encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, or to a peptide thereof that comprises an amino acid variation from the corresponding sequence encoded by the TOI-encoding nucleotide sequence having the highest cumulative human allele frequency and/or the highest total human genotype frequency, and isolating an antibody that binds a TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, and optionally producing a TOI-binding fragment or derivative of the isolated antibody.\",\n \"In a Ninth Configuration A kit for TOI genotyping a human, wherein the kit comprises a nucleic acid comprising a nucleotide sequence that specifically hybridises to a TOI nucleotide sequence selected having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50% or an RNA transcript thereof; and/or the nucleic acid comprises a nucleotide sequence that comprises at least 10 contiguous nucleotides of a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50% or is an antisense sequence thereof.\",\n \"In a Tenth Configuration Use of an anti-TOI ligand that binds a human TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, in the manufacture of a medicament for treating and/or preventing a TOI-mediated disease or condition in a human whose genome comprises a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.\",\n \"In a Eleventh Configuration Use of an anti-TOI ligand that binds a human TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, in the manufacture of a medicament for targeting said TOI in a human to treat and/or prevent a disease or condition mediated by TOI.\",\n \"In a Twelfth Configuration A method of targeting a TOI for treating and/or preventing a TOI-mediated disease or condition in a human, the method comprising administering an anti-TOI ligand to a human comprising a TOI nucleotide sequence selected having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, whereby a TOI encoded by said nucleotide sequence is targeted.\",\n \"In a Thirteenth Configuration A method of TOI genotyping a nucleic acid sample of a human, the method comprising identifying in the sample the presence of a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.\",\n \"In a Fourteenth Configuration A method of TOI typing a protein sample of a human, the method comprising identifying in the sample the presence of a TOI amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.\",\n \"In an example, the TOI is a human TOI selected from the group consisting of PCSK9, VEGF-A and IL6 receptor.\",\n \"A Fifteenth Configuration provides a ligand, method, use, kit or composition of the invention, wherein (i) the ligand (eg, antibody or fragment) comprises (a) a variable domain that is encoded by a human V region nucleotide sequence, wherein the V nucleotide sequence is derived from recombination of human VH, D and JH gene segments or human VL and JL gene segments; or (b) a constant region domain encoded by a C region gene segment; Wherein a first gene segment of said gene segments of (a), or said C region gene segment of (b) comprises a first single nucleotide polymorphism (SNP) encoding a first amino acid polymorphism; and (ii) the genome of said human comprises said first SNP or wherein said human expresses (a′) an antibody variable domain comprising said first amino acid polymorphism or (b′) an antibody constant domain comprising said first amino acid polymorphism.\",\n \"A Sixteenth Configuration provides the ligand, method, use, kit or composition of the invention, wherein the ligand comprises or consists of an antibody or fragment that comprises a human antibody variable domain derived from the recombination of a human V gene segment and a human J gene segment (and optionally a human D gene segment when the variable domains are VH domains); and wherein the genome of the human comprises said human V gene segment and/or the human expresses antibodies comprising antibody variable domains derived from the recombination of said human V gene segment and a human J gene segment (and optionally a human D gene segment).\",\n \"A Sixteenth Configuration provides the ligand, method, use, kit or composition of the invention, wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused human PCSK9 receptor) comprises a human heavy chain constant domain encoded by a first constant region nucleotide sequence; and wherein the genome of the human comprises a heavy chain constant region nucleotide sequence that is identical to said first constant region nucleotide sequence and/or the human expresses antibodies comprising said human constant domain.\",\n \"A Seventeenth Configuration provides the ligand, method, use, kit or composition of the invention, wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused TOI receptor) comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 or a Leu corresponding to position 206 of SEQ ID NO: 42 and wherein the genome of the human comprises a gamma-1 heavy chain constant region nucleotide sequence that encodes such an Asp or Leu or the human expresses antibodies comprising human gamma-1 constant regions comprising such an Asp or Leu.\",\n \"A Eighteenth Configuration provides the ligand, method, use, kit or composition of the invention, wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused TOI receptor) comprises a human gamma-2 heavy chain constant region that comprises an amino acid selected from the group consisting of a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44, a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44; and wherein the genome of the human comprises a gamma-2 heavy chain constant region nucleotide sequence that encodes such a selected amino acid or the human expresses antibodies comprising human gamma-2 constant regions comprising such a selected amino acid.\",\n \"A Nineteenth Configuration provides the ligand, method, use, kit or composition of the invention, wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused TOI receptor) comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 or a Cys corresponding to position 87 of SEQ ID NO: 50; and wherein the genome of the human comprises a kappa light chain constant region nucleotide sequence that encodes such a Val or Cys or the human expresses antibodies comprising human kappa light chain constant regions comprising such a Val or Cys.\",\n \"A Twentieth Configuration provides the ligand, method, use, kit or composition of the invention, wherein the ligand comprises or consists of an antibody or fragment, wherein the antibody or fragment comprises a VH domain that is derived from the recombination of a human VH gene segment, a human D gene segment and a human JH gene segment, wherein the VH gene segment is selected from the group consisting of (i) IGHV1-18*01 and the genome of the human comprises a human IGHV1-18*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGHV1-18*01; or (ii) IGVH1-46*01 and the genome of the human comprises a human IGHV1-46*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGHV1-46*01.A Twenty-First Configuration provides the ligand, method, use, kit or composition of the invention, wherein the ligand comprises or consists of an antibody or fragment, wherein the antibody or fragment comprises a VL domain that is derived from the recombination of a human VL gene segment and a human JL gene segment, wherein the VL gene segment is selected from the group consisting of (i) IGKV4-1*01 and the genome of the human comprises a human IGKV4-1*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGKV4-1*01; (ii) IGLV2-14*01 and the genome of the human comprises a human IGLV2-14*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGLV2-14*01; or (iii) IGKV1-13*02 and the genome of the human comprises a human IGKV1-13*02 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGKV1-13*02.BRIEF DESCRIPTION OF THE DRAWINGS This patent or application file contains at least one drawing executed in color.\",\n \"Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.\",\n \"FIG.\",\n \"1 shows in silico modeling of PCSK9 surface variant residues.\",\n \"FIG.\",\n \"2 depicts the cumulative allele frequency distribution across the 1000 Genomes Project database of human VH3-23 alleles comprising SNP rs56069819 (such alleles denoted “C” and the most frequent allele (which does not comprise this SNP) denoted “A”).\",\n \"The figure shows that VH3-23 alleles comprising SNP rs56069819 are present at a cumulative frequency of 11% across all human ethnic populations taken as a whole, whereas in certain specific human ethnic sub-populations (ASW, LWK, YRI, CEU and GBR) such alleles are present at an above-average cumulative frequency.\",\n \"Indicated in the figure are those human PCSK9 variant forms (marked “Variants”) that are found in the various sub-populations with above-average occurrence of human VH3-23 alleles comprising SNP rs56069819.FIG.\",\n \"3 depicts frameworks and CDRs encoded by VH3-23*04 as obtained from the IMGT database (available on the World Wide Web at www.IMGT.org).\",\n \"FIG.\",\n \"3 discloses the nucleotide sequences as SEQ ID NOS 68, 68, 68, 70, 70, 70, 71, 73, 75, 39 and 76, respectively, in order of appearance.\",\n \"FIG.\",\n \"3 discloses the coded amino acid sequences as SEQ ID NOS 69, 69, 69, 69, 69, 69, 72, 74, 74, 38 and 77, respectively, in order of appearance.\",\n \"FIG.\",\n \"4 depicts sequences of VH3-23*04.The portion of VH3-23*04 comprising the FW1 residue change of rs56069819 (SEQ ID NO: 38).\",\n \"The portion of the nucleic acid sequence encoding rs56069819 is depicted (SEQ ID NO: 39).\",\n \"The FW1 encoded by VH3-23*04 is depicted (SEQ ID NO: 40).\",\n \"DETAILED DESCRIPTION The skilled person will know that SNPs or other changes that translate into amino acid variation can cause variability in conformation or activity of human targets to be addressed.\",\n \"This has spawned great interest in personalized medicine where genotyping and knowledge of protein and nucleotide variability is used to tailor medicines and diagnosis of patients more effectively.\",\n \"The present invention provides for tailored pharmaceuticals and testing that specifically addresses rarer variant forms of a human target of interest (TOI).\",\n \"The present invention harnesses the power of human genetic variation analysis and rationally-designed sequence selection.\",\n \"The technical applications of these approaches, as per the present invention, contribute to better treatment, prophylaxis and diagnosis in humans and provides for patient benefit by providing choice and enabling personalized medicines and therapies.\",\n \"This provides advantages of better prescribing, less wastage of medications and improved chances of drug efficacy and better diagnosis in patients.\",\n \"As sources of genomic sequence variation data, the skilled person will be aware of the available databases and resources (including updates thereof) provided by the following:— 1.HapMap (The International HapMap Consortium.\",\n \"2003; available on the World Wide Web at hapmap.ncbi.nlm.nih.gov/index.html.en).\",\n \"The HapMap Project is an international project that aims to compare the genetic sequences of different individuals to identify chromosomal regions containing shared genetic variants.\",\n \"The HapMap www site provides tools to identify chromosomal regions and the variant therein, with options to drill down to population level frequency data.\",\n \"2.1000 Genomes Project (The 1000 Genomes Project Consortium 2010; available on the World Wide Web at 1000genomes.org/).\",\n \"This resource provides complete genomic sequence for at least 2500 unidentified individuals from one of 25 distinct population groups.\",\n \"3.Japanese SNP Database (H. Haga et al.\",\n \"2002; available on the World Wide Web at snp.ims.u-tokyo.ac.jp/index.html).\",\n \"Based on a study identifying 190,562 human genetic variants.\",\n \"The present invention involves the identification and cataloguing of naturally-occurring human genomic target sequence variants, including those found to be relatively low-frequency or rare variants that segregate with specific human ethnic populations and in many individual humans.\",\n \"An aspect of the invention is based on rational design of sequence selection addressing the desirability to tailor medicaments and diagnostics to rarer, but yet still significant groups of human individuals that suffer from, or have the potential to suffer from (ie, who are at risk of), a disease or condition mediated or associated with the target of interest.\",\n \"In devising this rational design of the present aspect of the invention, the inventor included considerations of the spread of prevalence of naturally-occurring target variant sequences across multiple, diverse human ethnic populations, as well as the importance of addressing such populations where many individuals are likely to display a genotype and/or phenotype of one or more of the variants being analysed.\",\n \"As part of this design, the inventor saw the importance of adopting the art-recognised classifications of human ethnic populations, and in this respect the inventor based the analysis and design on the recognised human ethnic populations adopted by the 1000 Genomes Project, since this is a resource that is, and will continue to be, widely adopted by the scientific and medical community.\",\n \"Thus, in this aspect of the invention, the inventor designed the following variant sequence selection criteria, these being criteria that the inventor realised would provide for useful medical drugs and diagnostics to tailored need in the human population.\",\n \"Selection Criteria Three or four of the following:— Naturally-occurring human target variant sequences having a cumulative human allele frequency of 35% or less; Naturally-occurring human target variant sequences having a total human genotype frequency of 40% or less; Naturally-occurring human target variant sequences found in many different human ethnic populations (using the standard categorisation of the 1000 Genomes Project; see Table 4 below); and Naturally-occurring human target variant sequences found in many individuals distributed across such many different ethnic populations.\",\n \"The inventor's selection included, as a consideration, selection for nucleotide variation that produced amino acid variation in corresponding TOI forms (ie, non-synonymous variations), as opposed to silent variations that do not alter amino acid residues in the target protein.\",\n \"In an embodiment, the cumulative human allele frequency is 30, 25, 20, 15, 10 or 5% or less, eg, in the range from 1 to 20% or 1 to 15% or 1 to 10%.\",\n \"In an embodiment, the total human genotype frequency is 35, 30, 25, 20, 15, 10 or 5% or less, eg, in the range from 1 to 25%, 1 to 20%, 1 to 15%, 1 to about 15%, 1 to 10%, 1 to about 10% or 1 to 5% or 1 to about 5%.\",\n \"In an embodiment, the naturally-occurring human target variant sequences are found in at least 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 different human ethnic populations (using the standard categorisation of the 1000 Genomes Project).\",\n \"In an embodiment, the naturally-occurring human target variant sequences are found in at least 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 130, 140 or 150 individuals distributed across such many different ethnic populations.\",\n \"In an example, the following criteria are applied:— Naturally-occurring human target variant sequences having a cumulative human allele frequency of 15% or less; Naturally-occurring human target variant sequences having a total human genotype frequency of 20% or less; Naturally-occurring human target variant sequences found in at least 5 different human ethnic populations (using the standard categorisation of the 1000 Genomes Project); and Naturally-occurring human target variant sequences found in many individuals distributed across such many different ethnic populations.\",\n \"In an example, the criteria are applied with reference to one or more human genomic sequence databases as described herein.\",\n \"For example, the criteria are those as applied to the 1000 Genomes database.\",\n \"For example in any aspect example, embodiment or configuration of the invention, the 1000 Genomes database release 13.For example, the 1000 Genomes database in its most recent version as at 1 Oct. 2013.Optionally, further sequence analysis and 3D in silico modelling (eg, see FIG.\",\n \"1) can also be used as an additional selection criterion: variants whose variant amino acid residues (versus the most common form of human TOI) are surface-exposed on the target are desirable for selection, since the inventor saw these as contributing to determining the topography of the target and potentially contributing to how and where ligand binding on the target occurs.\",\n \"The following bioinformatics protocol is envisaged to identify human sequences for use in the present invention: (a) Identify a genomic region containing a target sequence of interest (‘target genomic region’) and calculate the genomic coordinates, using coordinates that match the sequence assembly build used by either the 1000 Genomes Project or International HapMap project (or another selected human gene database of choice).\",\n \"(b) Identify genomic variants mapped to the genomic region previously identified in (a).\",\n \"Retrieve allele frequencies for variants for each super population and preferably sub-population where such data is available.\",\n \"The VWC tools for the 1000 Genomes Project can be used for this step.\",\n \"(c) Filter list of genomic variants from target genomic region to contain only variants classed as either ‘non-synonymous’ single nucleotide polymorphisms (SNPs) or genomic ‘insertions or deletions’ (indels).\",\n \"Filter further to include those that are present in exonic sequences only.\",\n \"“Non-synonymous” refers to nucleotide variation that produces amino acid variation (ie, excluding silent mutations).\",\n \"(d) Correlate population frequency data for each of the identified variants for each of the super populations (for example ‘European Ancestry’, ‘East Asian ancestry’, ‘West African ancestry’, ‘Americas’, and ‘South Asian ancestry’) to identify those variants that segregate with less than two super-populations.\",\n \"Further correlate all identified variants with each of the sub-populations (for example, ‘European ancestry’ super-population might be subdivided into groups such as ‘CEU—Utah residents with Northern or Western European ancestry’, ‘TSI Toscani in Italia’ and ‘British from England and Scotland’) and produce a second score for rarity of variants within a super-population.\",\n \"(e) Collect one or more sequences that show segregation to specific sub-populations for use in the present invention, eg, according to selection criteria as described herein.\",\n \"Human Populations Optionally the ethnic populations are selected from those identified in the 1000 Genomes Project database.\",\n \"In this respect, see Table 4 which provides details of the ethnic populations on which the 1000 Genomes Project database is based.\",\n \"N A Rosenberg et al (Science 20 Dec. 2002: vol.\",\n \"298 no.\",\n \"5602 2342-2343) studied the genetic structure of human populations of differing geographical ancestry.\",\n \"In total, 52 populations were sampled, these being populations with: African ancestry (Mbuti Pygmies, Biaka Pygmies, San peoples, and speakers of Niger-Kordofanian languages (Bantu, Yoruba or Mandenka populations), Eurasian ancestry (European ancestry (Orcadian, Adygel, Basque, French, Russians, Italians, Sardinian, Tuscan), Middle Eastern ancestry (Mozabite, Bedouin, Druze, Palestinians), Central/South Asian ancestry (Balochl, Brahul, Makrani, Sindhi, Pathan, Burusho, Hazara, Uygur, Kalash)), East Asian ancestry (Han, Dal, Daur, Hezhen, Lahu, Miao, Oroqen, She, Tujia, Tu, Xibo, Yi, Mongola, Naxi, Cambodian, Japanese, Yakut), Oceanic ancestry (Melanesian, Papuan); or Americas ancestry (Karitiana, Surui, Colombian, Maya, Pima).\",\n \"The International HapMap Project, Nature, 2003 Dec. 18; 426(6968):789-96, discloses that goal of the HapMap Project: to determine the common patterns of DNA sequence variation in the human genome by determining the genotypes of one million or more sequence variants, their frequencies and the degree of association between them in DNA samples from populations with ancestry from parts of Africa, Asia and Europe.\",\n \"The relevant human populations of differing geographical ancestry include Yoruba, Japanese, Chinese, Northern European and Western European populations.\",\n \"More specifically:— Utah population with Northern or Western European ancestry (samples collected in 1980 by the Centre d'Etude du Polymorphisme Humain (CEPH)); population with ancestry of Yoruba people from Ibadan, Nigeria; population with Japanese ancestry; and population with ancestry of Han Chinese from China.\",\n \"The authors, citing earlier publications, suggest that ancestral geography is a reasonable basis for sampling human populations.\",\n \"A suitable sample of human populations used in the present invention is as follows:— (a) European ancestry (b) Northern European ancestry; Western European ancestry; Toscani ancestry; British ancestry, Finnish ancestry or Iberian ancestry.\",\n \"(c) More specifically, population of Utah residents with Northern and/or Western European ancestry; Toscani population in Italia; British population in England and/or Scotland; Finnish population in Finland; or Iberian population in Spain.\",\n \"(a) East Asian ancestry (b) Japanese ancestry; Chinese ancestry or Vietnamese ancestry.\",\n \"(c) More specifically, Japanese population in Tokyo, Japan; Han Chinese population in Beijing, China; Chinese Dai population in Xishuangbanna; Kinh population in Ho Chi Minh City, Vietnam; or Chinese population in Denver, Colo., USA.\",\n \"(a) West African ancestry (b) Yoruba ancestry; Luhya ancestry; Gambian ancestry; or Malawian ancestry.\",\n \"(c) More specifically, Yoruba population in Ibadan, Nigeria; Luhya population in Webuye, Kenya; Gambian population in Western Division, The Gambia; or Malawian population in Blantyre, Malawi.\",\n \"(a) Population of The Americas (b) Native American ancestry; Afro-Caribbean ancestry; Mexican ancestry; Puerto Rican ancestry; Columbian ancestry; or Peruvian ancestry.\",\n \"(c) More specifically, population of African Ancestry in Southwest US; population of African American in Jackson, Miss.\",\n \"; population of African Caribbean in Barbados; population of Mexican Ancestry in Los Angeles, Calif.; population of Puerto Rican in Puerto Rico; population of Colombian in Medellin, Colombia; or population of Peruvian in Lima, Peru.\",\n \"(a) South Asian ancestry (b) Ahom ancestry; Kayadtha ancestry; Reddy ancestry; Maratha; or Punjabi ancestry.\",\n \"(c) More specifically, Ahom population in the State of Assam, India; Kayadtha population in Calcutta, India; Reddy population in Hyderabad, India; Maratha population in Bombay, India; or Punjabi population in Lahore, Pakistan.\",\n \"In any configuration of the invention, in one embodiment, each human population is selected from a population marked “(a)” above.\",\n \"In any configuration of the invention, in another embodiment, each human population is selected from a population marked “(b)” above.\",\n \"In any configuration of the invention, in another embodiment, each human population is selected from a population marked “(c)” above.\",\n \"In one embodiment the ethnic populations are selected from the group consisting of an ethnic population with European ancestry, an ethnic population with East Asian, an ethnic population with West African ancestry, an ethnic population with Americas ancestry and an ethnic population with South Asian ancestry.\",\n \"In one embodiment the ethnic populations are selected from the group consisting of an ethnic population with Northern European ancestry; or an ethnic population with Western European ancestry; or an ethnic population with Toscani ancestry; or an ethnic population with British ancestry; or an ethnic population with Icelandic ancestry; or an ethnic population with Finnish ancestry; or an ethnic population with Iberian ancestry; or an ethnic population with Japanese ancestry; or an ethnic population with Chinese ancestry; or an ethnic population Vietnamese ancestry; or an ethnic population with Yoruba ancestry; or an ethnic population with Luhya ancestry; or an ethnic population with Gambian ancestry; or an ethnic population with Malawian ancestry; or an ethnic population with Native American ancestry; or an ethnic population with Afro-Caribbean ancestry; or an ethnic population with Mexican ancestry; or an ethnic population with Puerto Rican ancestry; or an ethnic population with Columbian ancestry; or an ethnic population with Peruvian ancestry; or an ethnic population with Ahom ancestry; or an ethnic population with Kayadtha ancestry; or an ethnic population with Reddy ancestry; or an ethnic population with Maratha; or an ethnic population with Punjabi ancestry.\",\n \"Anti-Target Ligands The invention provides useful anti-target ligands for addressing humans suffering from or likely to suffer from a disease or condition mediated or associated with the TOI.\",\n \"For example, the ligand specifically binds to the TOI variant as per the invention.\",\n \"The ligand may inhibit or antagonise the activity of the target, eg, the ligand neutralises the target.\",\n \"The skilled person will be familiar with neutralising ligands in general, such as antibodies or antibody fragments, and can readily test suitable ligands for specific binding and/or neutralisation of a target in vitro or in an in vivo assay.\",\n \"An antibody “fragment” comprises a portion of an intact antibody, preferably the antigen binding and/or the variable region of the intact antibody.\",\n \"Examples of antibody fragments include dAb, Fab, Fab′, F(ab′)2 and Fv fragments; diabodies; linear antibodies; single-chain antibody molecules and multispecific antibodies formed from antibody fragments.\",\n \"In an embodiment, the ligand of the invention is or comprises an antibody or antibody fragment, for example an antibody or fragment comprising human variable regions (and optionally also human constant regions).\",\n \"Anti-TOI or TOI-binding or targeting antibodies and fragments can be prepared according to any known method, eg, using transgenic mice (eg, the Kymouse™ or Velocimouse™, or Omnimouse™, Xenomouse™, HuMab Mouse™ or MeMo Mouser™), rats (eg, the Omnirat™), camelids, sharks, rabbits, chickens or other non-human animals immunised with the TOI followed optionally by humanisation of the constant regions and/or variable regions to produce human or humanised antibodies.\",\n \"In an example, display technologies can be used, such as yeast, phage or ribosome display, as will be apparent to the skilled person.\",\n \"Standard affinity maturation, eg, using a display technology, can be performed in a further step after isolation of an antibody lead from a transgenic animal, phage display library or other library.\",\n \"Representative examples of suitable technologies are described in US20120093818 (Amgen, Inc), which is incorporated herein by reference, eg, the methods set out in paragraphs [0309] to [0346].\",\n \"Although this is with reference to PCSK9, the antibody-generating methods can be applied to other TOIs as per the broadest scopes of the present invention.\",\n \"Generally, a VELOCIMMUNE™ or other mouse or rat can be challenged with the antigen of interest, and lymphatic cells (such as B-cells) are recovered from the mice that express antibodies.\",\n \"The lymphatic cells may be fused with a myeloma cell line to prepare immortal hybridoma cell lines, and such hybridoma cell lines are screened and selected to identify hybridoma cell lines that produce antibodies specific to the antigen of interest.\",\n \"DNA encoding the variable regions of the heavy chain and light chain may be isolated and linked to desirable isotypic constant regions of the heavy chain and light chain.\",\n \"Such an antibody protein may be produced in a cell, such as a CHO cell.\",\n \"Alternatively, DNA encoding the antigen-specific chimaeric antibodies or the variable domains of the light and heavy chains may be isolated directly from antigen-specific lymphocytes.\",\n \"Initially, high affinity chimaeric antibodies are isolated having a human variable region and a mouse constant region.\",\n \"As described below, the antibodies are characterized and selected for desirable characteristics, including affinity, selectivity, epitope, etc.\",\n \"The mouse constant regions are replaced with a desired human constant region to generate the fully human antibody of the invention, for example wild-type or modified IgG1 or IgG4 (for example, SEQ ID NO: 751, 752, 753 in US2011/0065902, which sequences are incorporated herein by reference for use in the ligands of the present invention).\",\n \"While the constant region selected may vary according to specific use, high affinity antigen-binding and target specificity characteristics reside in the variable region.\",\n \"In an example, the ligand of the invention is or comprises a nucleic acid, eg, RNA, eg, siRNA that hybridises under stringent condition to the TOI variant sequence, eg, hybridises a nucleotide sequence comprising one or more nucleotides that are variant (versus the most common TOI sequence, eg, with reference to the 1000 Genomes Project database).\",\n \"Target binding ability, specificity and affinity (Kd, Koff and/or Kon) can be determined by any routine method in the art, eg, by surface plasmon resonance (SPR).\",\n \"The term “Kd”, as used herein, is intended to refer to the equilibrium dissociation constant of a particular antibody-antigen interaction.\",\n \"In one embodiment, the surface plasmon resonance (SPR) is carried out at 25° C. In another embodiment, the SPR is carried out at 37° C. In one embodiment, the SPR is carried out at physiological pH, such as about pH7 or at pH7.6 (eg, using Hepes buffered saline at pH7.6 (also referred to as HBS-EP)).\",\n \"In one embodiment, the SPR is carried out at a physiological salt level, eg, 150 mM NaCl.\",\n \"In one embodiment, the SPR is carried out at a detergent level of no greater than 0.05% by volume, eg, in the presence of P20 (polysorbate 20; eg, Tween-20™) at 0.05% and EDTA at 3 mM.\",\n \"In one example, the SPR is carried out at 25° C. or 37° C. in a buffer at pH7.6, 150 mM NaCl, 0.05% detergent (eg, P20) and 3 mM EDTA.\",\n \"The buffer can contain 10 mM Hepes.\",\n \"In one example, the SPR is carried out at 25° C. or 37° C. in HBS-EP.\",\n \"HBS-EP is available from Teknova Inc (California; catalogue number H8022).\",\n \"In an example, the affinity of the ligand (eg, antibody) is determined using SPR by 1.Coupling anti-mouse (or other relevant human, rat or non-human vertebrate antibody constant region species-matched) IgG (eg, Biacore™ BR-1008-38) to a biosensor chip (eg, GLM chip) such as by primary amine coupling; 2.Exposing the anti-mouse IgG (or other matched species antibody) to a test IgG antibody to capture test antibody on the chip; 3.Passing the test antigen over the chip's capture surface at 1024 nM, 256 nM, 64 nM, 16 nM, 4 nM with a 0 nM (i.e.\",\n \"buffer alone); and 4.And determining the affinity of binding of test antibody to test antigen using surface plasmon resonance, eg, under an SPR condition discussed above (eg, at 25° C. in physiological buffer).\",\n \"SPR can be carried out using any standard SPR apparatus, such as by Biacore™ or using the ProteOn XPR36™ (Bio-Rad®).\",\n \"Regeneration of the capture surface can be carried out with 10 mM glycine at pH1.7.This removes the captured antibody and allows the surface to be used for another interaction.\",\n \"The binding data can be fitted to 1:1 model inherent using standard techniques, eg, using a model inherent to the ProteOn XPR36™ analysis software.\",\n \"In an example, the ligand of the invention is contained in a medical container, eg, a vial, syringe, IV container or an injection device (eg, an intraocular or intravitreal injection device).\",\n \"In an example, the ligand is in vitro, eg, in a sterile container.\",\n \"In an example, the invention provides a kit comprising the ligand of the invention, packaging and instructions for use in treating or preventing or diagnosing in a human a disease or condition mediated by the TOI.\",\n \"In an example, the instructions indicate that the human should be genotyped for a TOI variant sequence of the invention before administering the ligand to the human.\",\n \"In an example, the instructions indicate that the human should be phenotyped for a TOI variant of the invention before administering the ligand to the human.\",\n \"In an example, the human is of Chinese (eg, Han) ethnicity and the instructions are in Chinese (eg, Mandarin).\",\n \"In an example, the instructions comprise directions to administer alirocumab or evolocumab to said human.\",\n \"The invention relates to the concepts set out in the following clauses.\",\n \"Clause 1 A method of treating or preventing a disease or condition in a human, wherein the disease or condition is mediated by a Target of Interest (TOI), wherein the TOI is present in humans as different polymorphic variants, the method comprising a.\",\n \"Administering to the human an anti-TOI ligand to target a TOI variant in the human and treat or prevent (eg, by at least 40, 50, 60, 70, 80, 90 or 95%) said disease or condition, wherein the TOI in said human is encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or wherein the TOI in said human is encoded by a nucleotide sequence having a total human genotype frequency of less than 50%; wherein Before step (a) said human has been or is genotyped as positive for said nucleotide sequence or phenotyped as positive for said TOI variant, or the method comprises before step (a) genotyping the human as positive for said nucleotide sequence or phenotyping the human as positive for said TOI variant.\",\n \"In any aspect, configuration, example, embodiment, clause or concept herein, frequencies may be determined using bioinformatics.\",\n \"In any aspect, configuration, example, embodiment, clause or concept herein, frequencies may be determined by reference to a database comprising at least 1000 or 2000 human sequences.\",\n \"In any aspect, configuration, example, embodiment, clause or concept herein “heterozygous human genotype frequency” means the cumulative frequency of all genotypes in the sample or database or in humans having one occurrence of the rare variant allele and one occurrence of another allele (heterozygous state), eg, genotype in 1000 Genomes database.\",\n \"In any aspect, configuration, example, embodiment, clause or concept herein “homozygous human genotype frequency means the cumulative frequency of two occurrences of the variant allele (homozygous state), eg, genotype in 1000 Genomes Project database.\",\n \"In any aspect, configuration, example, embodiment, clause or concept herein “total human genotype frequency” means the total of heterozygous plus homozygous human genotype frequencies.\",\n \"In any aspect, configuration, example, embodiment, clause or concept herein “cumulative human allele frequency” refers to the total of all occurrences of the variant allele in the sample or database or in humans, eg, in the 1000 Genomes Project database.\",\n \"Clause 2: The method of clause 1, wherein before step (a) the ligand has been or is determined as being capable of binding to said TOI variant, eg, with an affinity (Kd) disclosed below.\",\n \"In an example, the ligand is (or has been determined as) a neutraliser of the TOI.\",\n \"In an example, determination is carried out in a human (eg, in a clinical trial).\",\n \"In an example, determination is carried out in a non-human, eg, in a mouse, rat, rabbit, pig, dog, sheep or non-human primate (eg, Cynomolgous monkey, rhesus monkey or baboon).\",\n \"Clause 3: A method of treating or preventing a disease or condition in a human, wherein the disease or condition is mediated by a Target of Interest (TOI), wherein the TOI is present in humans as different polymorphic variants, the method comprising a.\",\n \"Administering to the human an anti-TOI ligand to target a TOI variant in the human and treat or prevent (eg, by at least 40, 50, 60, 70, 80, 90 or 95%) said disease or condition, wherein the TOI in said human is encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or wherein the TOI in said human is encoded by a nucleotide sequence having a total human genotype frequency of less than 50%; wherein b.\",\n \"Before step (a) the ligand has been or is determined as capable of binding to said TOI variant, eg, with an affinity (Kd) disclosed below.\",\n \"In an example, the ligand is (or has been determined as) a neutraliser of the TOI.\",\n \"In an example, determination is carried out in a human (eg, in a clinical trial).\",\n \"In an example, determination is carried out in a non-human, eg, in a mouse, rat, rabbit, pig, dog, sheep or non-human primate (eg, Cynomolgous monkey, rhesus monkey or baboon).\",\n \"Clause 4: The method of clause 3, wherein the genome of said human comprises a nucleotide sequence encoding said TOI variant; and before step (a) said nucleotide sequence has been or is determined as having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.\",\n \"The TOI variant is not the most frequent.\",\n \"Clause 5: The method of clause 3 or 4, wherein said human has been or is genotyped as positive for said variant nucleotide sequence before step (a), or the method comprises genotyping the human as positive for said variant nucleotide sequence before step (a).\",\n \"Clause 6: The method of any preceding clause, wherein the human has been or is phenotyped as positive for said TOI variant before step (a), or the method comprises phenotyping the human as positive for said variant nucleotide sequence before step (a).\",\n \"Clause 7: The method of any preceding clause, wherein said frequency is less than 10 or 15% (eg, from 1 to 10%).\",\n \"In an embodiment, the cumulative human allele frequency is 30, 25, 20, 15, 10 or 5% or less, eg, in the range from 1 to 20% or 1 to 15% or 1 to 10%.\",\n \"In an embodiment, the total human genotype frequency is 35, 30, 25, 20, 15, 10 or 5% or less, eg, in the range from 1 to 25%, 1 to 20%, 1 to 15%, 1 to about 15%, 1 to 10%, 1 to about 10% or 1 to 5% or 1 to about 5%.\",\n \"Clause 8: The method of any preceding clause, wherein the ligand is capable of binding to two or more different TOI variants, each being encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% (eg, from 1 to 10%) and/or having a total human genotype frequency of less than 50% (eg, from 1 to 20%).\",\n \"In an embodiment, the cumulative human allele frequency of each TOI variant is 30, 25, 20, 15, 10 or 5% or less, eg, in the range from 1 to 20% or 1 to 15% or 1 to 10%.\",\n \"In an embodiment, the total human genotype frequency of each TOI variant is 35, 30, 25, 20, 15, 10 or 5% or less, eg, in the range from 1 to 25%, 1 to 20%, 1 to 15%, 1 to about 15%, 1 to 10%, 1 to about 10% or 1 to 5% or 1 to about 5%.\",\n \"Clause 9: A method of treating or preventing a disease or condition in a human, wherein the disease or condition is mediated by a Target of Interest (TOI), wherein the TOI is present in humans as different polymorphic variants, the method comprising a.\",\n \"Administering to the human an anti-TOI ligand to target a TOI variant in the human and treat or prevent (eg, by at least 40, 50, 60, 70, 80, 90 or 95%) said disease or condition, wherein the TOI in said human is a variant encoded by a nucleotide sequence having a cumulative human allele frequency of more than 50% (eg, the highest frequency) and/or having a total human genotype frequency of more than 50% (eg, the highest frequency); wherein b.\",\n \"Before step (a) said human has been or is genotyped as negative for a variant nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%; or phenotyped as negative for a TOI variant encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%; or Before step (a) said the method comprises genotyping the human as negative for a variant nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%; or phenotyping the human as negative for a TOI variant encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.\",\n \"In an embodiment, in (a) the cumulative human allele frequency is 55, 60, 65, 70, 75, 80, 85 or 90 or more but less than 95, 96, 97, 98, 99 or 100% (eg, in the range from 51 to 80%).\",\n \"In an embodiment, in (a) the total human genotype frequency is 55, 60, 65, 70, 75, 80, 85 or 90 or more but less than 95, 96, 97, 98, 99 or 100% (eg, in the range from 51 to 80%).\",\n \"In an embodiment, in (b) the cumulative human allele frequency is 30, 25, 20, 15, 10 or 5% or less, eg, in the range from 1 to 20% or 1 to 15% or 1 to 10%.\",\n \"In an embodiment, in (b) the total human genotype frequency is 35, 30, 25, 20, 15, 10 or 5% or less, eg, in the range from 1 to 25%, 1 to 20%, 1 to 15%, 1 to about 15%, 1 to 10%, 1 to about 10% or 1 to 5% or 1 to about 5%.\",\n \"Clause 10: The method of clause 9, wherein before step (a), the human has been or is phenotyped as positive for the most frequent TOI variant or genotyped for the nucleotide sequence thereof.\",\n \"In an embodiment, before step (a) the human has been or is genotyped as positive for TOI variant nucleotide sequence having a cumulative human allele frequency of 55, 60, 65, 70, 75, 80, 85 or 90 or more but less than 95, 96, 97, 98, 99 or 100% (eg, in the range from 51 to 80%) or phenotyped for the TOI variant thereof.\",\n \"In an embodiment, before step (a) the human has been or is genotyped as positive for TOI variant nucleotide sequence having a total human genotype frequency of 55, 60, 65, 70, 75, 80, 85 or 90 or more but less than 95, 96, 97, 98, 99 or 100% (eg, in the range from 51 to 80%) or phenotyped for the TOI variant thereof.\",\n \"Clause 11: The method of clause 9 or 10, wherein before step (a) the ligand has been or is determined as being capable of binding to the most frequent TOI variant.\",\n \"Clause 12: The method of clause 9, 10 or 11, wherein before step (a) the ligand has been or is determined as being substantially incapable of neutralising or inhibiting said TOI variant recited in step (b).\",\n \"By “substantially incapable or neutralising or inhibiting” is meant: Neutralisation or inhibition less than 50, 25, 10, 5 or 0.5% inhibition or neutralisation of the most frequent TOI variant.\",\n \"Clause 13: The method of any one of clauses 9 to 12, wherein the ligand is capable of binding to the most frequent TOI variant.\",\n \"Clause 14: The method of any one of clauses 9 to 13, wherein the ligand is capable of binding to two or more different TOI variants, each being encoded by a nucleotide sequence having a cumulative human allele frequency of more than 50%.\",\n \"In an embodiment, each TOI variant is encoded by a nucleotide sequence having a cumulative human allele frequency of 55, 60, 65, 70, 75, 80, 85 or 90 or more but less than 95, 96, 97, 98, 99 or 100% (eg, in the range from 51 to 80%).\",\n \"In an embodiment, each TOI variant is encoded by a nucleotide sequence having a total human genotype frequency of 55, 60, 65, 70, 75, 80, 85 or 90 or more but less than 95, 96, 97, 98, 99 or 100% (eg, in the range from 51 to 80%).\",\n \"Clause 15: The method of any preceding clause, wherein said variant nucleotide sequence recited in step (a) has been or is determined as being present in at least 2 different human ethnic populations, eg, at least 2, 3, 4, 5, 6, 7, 8 or 9 different human ethnic populations in Table 4.Clause 16: The method of any preceding clause, wherein said human frequency is the frequency in a database of naturally-occurring sequences sampled from at least 15, 20 or 25 different human ethnic populations and comprising at least 1000 sequences.\",\n \"In an embodiment, the database is the 1000 Genomes Project database as described herein.\",\n \"Clause 17: An anti-human TOI ligand for use in a method of treating and/or preventing a TOI-mediated disease or condition in a human, wherein the TOI is present in humans as different polymorphic variants and wherein the genome of said human comprises a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, the method comprising administering the ligand to the human.\",\n \"In the alternative, clause 17 provides an anti-human TOI ligand for use in a method according to any one of clauses 1 to 16, the method comprising administering the ligand to the human.\",\n \"In an embodiment, the cumulative human allele frequency is 30, 25, 20, 15, 10 or 5% or less, eg, in the range from 1 to 20% or 1 to 15% or 1 to 10%.\",\n \"In an embodiment, the total human genotype frequency is 35, 30, 25, 20, 15, 10 or 5% or less, eg, in the range from 1 to 25%, 1 to 20%, 1 to 15%, 1 to about 15%, 1 to 10%, 1 to about 10% or 1 to 5% or 1 to about 5%.\",\n \"Clause 18: The ligand of clause 17, wherein the ligand has been or is determined as capable of binding the human TOI encoded by said nucleotide sequence.\",\n \"In the alternative, clause 18 provides a ligand that binds a human TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, for use in a method comprising the step of using the ligand to target said TOI in a human to treat and/or prevent a disease or condition mediated by TOI, the method comprising administering the ligand to the human.\",\n \"Clause 19: A ligand that binds a human TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, for use in a method according to any one of clauses 1 to 16, the method comprising administering the ligand to the human.\",\n \"Clause 20: The ligand of any one of clauses 17 to 19, wherein the human has been or is genotyped as positive for said TOI nucleotide sequence having a cumulative human allele frequency of less than 50%.\",\n \"The ligand of any one of clauses 17 to 19, wherein the human has been or is genotyped as positive for said TOI nucleotide sequence having a total human genotype frequency of less than 50%.\",\n \"Clause 21: The ligand of any one of clauses 17 to 20, wherein the human has been or is phenotyped as positive for a TOI encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.\",\n \"Clause 22: The ligand of any one of clauses 17 to 21, wherein the human has been or is genotyped as heterozygous for a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%; optionally wherein the human has been or is genotyped as comprising a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and a TOI nucleotide sequence having a cumulative human allele frequency of more than 50% (eg, having the highest cumulative human allele frequency) and/or having a total human genotype frequency of more than 50% (eg, having the highest total human genotype frequency).\",\n \"Clause 23: The ligand of any one of clauses 17 to 22, wherein the genome of the human has been or is genotyped as homozygous for a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.\",\n \"Clause 24: The ligand of any one of clauses 17 to 23, wherein the ligand comprises an antibody binding site that binds a human TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%; and optionally has been or is determined as capable of such binding.\",\n \"Clause 25: The ligand of clause 24, wherein the ligand is an antibody or antibody fragment.\",\n \"Clause 26: The ligand of any one of clauses 17 to 23, wherein the ligand comprises a nucleotide sequence that specifically hybridises to a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50% or an RNA transcript thereof, and/or the ligand comprises a nucleotide sequence that comprises at least 10 contiguous nucleotides of a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50% or is an antisense sequence thereof.\",\n \"In an embodiment, the ligand comprises a nucleotide sequence that comprises at least 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 50 or 100 contiguous nucleotides of a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50% or is an antisense sequence thereof.\",\n \"Clause 27: The ligand of any one of clauses 17 to 26, wherein the genome of said human comprises a nucleotide sequence having a cumulative human allele frequency of less than 50% and the sequence is found in at least 2 different ethnic populations (eg, found in at least 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 different human ethnic populations (for example as per the populations in Table 4)).\",\n \"In an example, numbers are with reference to the 1000 Genomes Project database.\",\n \"The ligand of any one of clauses 17 to 26, wherein the genome of said human comprises a nucleotide sequence having a cumulative human allele frequency of less than 50% and the sequence is found in at least 20 individuals distributed across at least 2 said different ethnic populations (eg, found in at least in at least 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 105, 110, 115, 120, 130, 140 or 150 individuals distributed across such many different ethnic populations).\",\n \"In an example, numbers are with reference to the 1000 Genomes Project database.\",\n \"Clause 28: A pharmaceutical composition or kit for treating or preventing a condition or disease mediated by a TOI as recited in any preceding clause, the composition or kit comprising a ligand of any one of clauses 17 to 27; and optionally in combination with a label or instructions for use to treat and/or prevent said disease or condition in a human; optionally wherein the label or instructions comprise a marketing authorisation number (eg, an FDA or EMA authorisation number); optionally wherein the kit comprises an injection pen or IV container that comprises the ligand.\",\n \"In an example, the label or instructions cover or describe use for a human comprising a TOI variant encoded by a nucleotide sequence as recited in clause 17.Clause 29: A method of producing an anti-human TOI antibody binding site, the method comprising obtaining a plurality of anti-TOI antibody binding sites, screening the antibody binding sites for binding to a TOI comprising an amino acid sequence encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, or to a peptide thereof that comprises an amino acid variation from the corresponding sequence encoded by the TOI-encoding nucleotide sequence having the highest cumulative human allele frequency and/or the highest total human genotype frequency, and isolating an antibody binding site that binds in the screening step.\",\n \"In an embodiment of any aspect herein, the antibody, fragment or binding site is recombinant.\",\n \"In the alternative, clause 29 provides: A method of producing an anti-human TOI antibody, the method comprising immunising a non-human vertebrate (eg, a mouse or a rat) with a TOI comprising an amino acid sequence encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, or to a peptide thereof that comprises an amino acid variation from the corresponding sequence encoded by the TOI-encoding nucleotide sequence having the highest cumulative human allele frequency and/or the highest total human genotype frequency, and isolating an antibody that binds a TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, and optionally producing a TOI-binding fragment or derivative of the isolated antibody.\",\n \"The term “isolated” with reference to a ligand, antibody or protein, for example in any aspect, configuration, example or embodiment, means that a subject ligand, antibody, protein etc (1) is free of at least some other proteins with which it would normally be found, (2) is essentially free of other proteins from the same source, e.g., from the same species, (3) is expressed by a cell from a different species, (4) has been separated from at least about 50 percent of polynucleotides, lipids, carbohydrates, or other materials with which it is associated in nature, (5) is operably associated (by covalent or noncovalent interaction) with a polypeptide with which it is not associated in nature, or (6) does not occur in nature.\",\n \"Typically, an “isolated” ligand, antibody, protein etc constitutes at least about 5%, at least about 10%, at least about 25%, or at least about 50% of a given sample.\",\n \"Genomic DNA, cDNA, mRNA or other RNA, of synthetic origin, or any combination thereof can encode such an isolated ligand, antibody protein etc.\",\n \"Preferably, the isolated ligand, antibody protein etc is substantially free from proteins or polypeptides or other contaminants that are found in its natural environment that would interfere with its therapeutic, diagnostic, prophylactic, research or other use.\",\n \"For example, an “isolated” antibody is one that has been identified, separated and/or recovered from a component of its production environment (eg, naturally or recombinantly).\",\n \"Preferably, the isolated polypeptide is free of association with all other components from its production environment, eg, so that the antibody has been isolated to an FDA-approvable or approved standard.\",\n \"Contaminant components of its production environment, such as that resulting from recombinant transfected cells, are materials that would typically interfere with research, diagnostic or therapeutic uses for the antibody, and may include enzymes, hormones, and other proteinaceous or non-proteinaceous solutes.\",\n \"In preferred embodiments, the polypeptide will be purified: (1) to greater than 95% by weight of antibody as determined by, for example, the Lowry method, and in some embodiments, to greater than 99% by weight; (2) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence by use of a spinning cup sequenator, or (3) to homogeneity by SDS-PAGE under non-reducing or reducing conditions using Coomassie blue or, preferably, silver stain.\",\n \"Isolated antibody includes the antibody in situ within recombinant cells since at least one component of the antibody's natural environment will not be present.\",\n \"Ordinarily, however, an isolated polypeptide or antibody will be prepared by at least one purification step.\",\n \"Immunoconjugates The invention encompasses the ligand (eg, antibody) conjugated to a therapeutic moiety (“immunoconjugate”), such as a cytotoxin, a chemotherapeutic drug, an immunosuppressant or a radioisotope.\",\n \"Cytotoxin agents include any agent that is detrimental to cells.\",\n \"Examples of suitable cytotoxin agents and chemotherapeutic agents for forming immunoconjugates are known in the art, see for example, WO 05/103081.Bispecifics The antibodies of the present invention may be monospecific, bispecific, or multispecific.\",\n \"Multispecific mAbs may be specific for different epitopes of one target polypeptide or may contain antigen-binding domains specific for more than one target polypeptide.\",\n \"See, e.g., Tutt et al.\",\n \"(1991) J. Immunol.\",\n \"147:60-69.The human anti-TOI (eg, anti-PCSK9) mAbs can be linked to or co-expressed with another functional molecule, e.g., another peptide or protein.\",\n \"For example, an antibody or fragment thereof can be functionally linked (e.g., by chemical coupling, genetic fusion, noncovalent association or otherwise) to one or more other molecular entities, such as another antibody or antibody fragment, to produce a bispecific or a multispecific antibody with a second binding specificity.\",\n \"An exemplary bi-specific antibody format that can be used in the context of the present invention involves the use of a first immunoglobulin (Ig) CH3 domain and a second Ig CH3 domain, wherein the first and second Ig CH3 domains differ from one another by at least one amino acid, and wherein at least one amino acid difference reduces binding of the bispecific antibody to Protein A as compared to a bi-specific antibody lacking the amino acid difference.\",\n \"In one embodiment, the first Ig CH3 domain binds Protein A and the second Ig CH3 domain contains a mutation that reduces or abolishes Protein A binding such as an H95R modification (by IMGT exon numbering; H435R by EU numbering).\",\n \"The second CH3 may further comprise a Y96F modification (by IMGT; Y436F by EU).\",\n \"Further modifications that may be found within the second CH3 include: D16E, L18M, N44S, K52N, V57M, and V821 (by IMGT; D356E, L358M, N384S, K392N, V397M, and V422I by EU) in the case of IgG1 antibodies; N44S, K52N, and V821 (IMGT; N384S, K392N, and V422I by EU) in the case of IgG2 antibodies; and Q15R, N44S, K52N, V57M, R69K, E79Q, and V821 (by IMGT; Q355R, N3845, K392N, V397M, R409K, E419Q, and V422I by EU) in the case of IgG4 antibodies.\",\n \"Variations on the bi-specific antibody format described above are contemplated within the scope of the present invention.\",\n \"Clause 30: The method of clause 29, comprising the step of obtaining a nucleic acid encoding the antibody, fragment, derivative or binding site and optionally inserting the nucleic acid in an expression vector.\",\n \"Clause 31: A kit for TOI genotyping a human, wherein the kit comprises a nucleic acid comprising a nucleotide sequence that specifically hybridises to a TOI nucleotide sequence selected having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50% or an RNA transcript thereof, and/or the nucleic acid comprises a nucleotide sequence that comprises at least 10 (eg, at least 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 50 or 100) contiguous nucleotides of a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50% or is an antisense sequence thereof.\",\n \"For example, the nucleic acid hybridises to a region immediately flanking a nucleotide that is variant compared to the corresponding nucleotide of the TOI nucleotide sequence having the highest cumulative human allele frequency and/or the highest total human genotype frequency.\",\n \"In an example, the nucleic acid hybridises to at two or more such variant nucleotides.\",\n \"Specific hybridisation is under stringent conditions, as will be apparent to the skilled person, eg, conditions of 5×SSC, 5×Denhardt's reagent, and 0.5% SDS at 65° C. Clause 32: A kit for TOI genotyping or phenotyping a human, wherein the kit comprises a ligand according to any one of clauses 17 to 27 or an antibody, fragment or derivative produced by the method of any one of clauses 29 to 31.For example, the ligand specifically binds to an epitope comprising an amino acid that is variant compared to the corresponding amino acid of the TOI encoded by a nucleotide sequence having the highest cumulative human allele frequency and/or the highest total human genotype frequency.\",\n \"In an example, the ligand specifically binds to an epitope comprising two or more such variant amino acids.\",\n \"In an example, specific binding means binding with an affinity (Kd) of 1 mM, 100 nM, 10 nM or 1 nM or less, eg, as determined by SPR.\",\n \"The term “epitope” is a region of an antigen that is bound by an antibody.\",\n \"Epitopes may be defined as structural or functional.\",\n \"Functional epitopes are generally a subset of the structural epitopes and have those residues that directly contribute to the affinity of the interaction.\",\n \"Epitopes may also be conformational, that is, composed of non-linear amino acids.\",\n \"In certain embodiments, epitopes may include determinants that are chemically active surface groupings of molecules such as amino acids, sugar side chains, phosphoryl groups, or sulfonyl groups, and, in certain embodiments, may have specific three-dimensional structural characteristics, and/or specific charge characteristics.\",\n \"Clause 33: Use of an anti-TOI ligand that binds a human TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, in the manufacture of a medicament for treating and/or preventing a TOI-mediated disease or condition in a human whose genome comprises a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.\",\n \"Clause 34: Use of an anti-TOI ligand that binds a human TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, in the manufacture of a medicament for targeting said TOI in a human to treat and/or prevent a disease or condition mediated by TOI.\",\n \"The use of clause 33 or 34, wherein the ligand, human, disease or condition is according to any one of clauses 1 to 27.Clause 35: A method of targeting a TOI for treating and/or preventing a TOI-mediated disease or condition in a human, the method comprising administering an anti-TOI ligand to a human comprising a TOI nucleotide sequence selected having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, whereby a TOI encoded by said nucleotide sequence is targeted.\",\n \"Clause 36: The method of clause 35, wherein the method comprises targeting a human TOI comprising an amino acid sequence with said ligand to treat and/or prevent said disease or condition in said human, wherein said amino acid sequence is encoded by a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%.\",\n \"Clause 37: A method of TOI genotyping a nucleic acid sample of a human, the method comprising identifying in the sample the presence of a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.\",\n \"In an example, the method comprises obtaining a TOI nucleic acid sample from the human and then carrying out the identifying step.\",\n \"Clause 38: A method of TOI typing a protein sample of a human, the method comprising identifying in the sample the presence of a TOI amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.\",\n \"In an example, the method comprises obtaining a TOI protein sample from the human and then carrying out the identifying step.\",\n \"Clause 39: The method of clause 37 or 38, comprising obtaining a sample of serum, blood, faeces, hair, urine or saliva from a human, whereby the nucleic acid or protein sample is obtained for use in the step of identifying said sequence.\",\n \"Clause 40: The method of any one of clauses 37 to 39, comprising using a ligand according to any one of clauses 17 to 27 to carry out said identifying step.\",\n \"Clause 41: A diagnostic kit comprising a ligand that is capable of binding a human TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50% and instructions for carrying out the method of clause 38 or 39.Clause 42: A diagnostic kit comprising a nucleic acid probe comprising a nucleotide sequence that specifically hybridises a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50% or an RNA transcript thereof and instructions for carrying out the method of clause 38 or 39.Clause 43: The method, ligand, composition, kit or use of any preceding clause, wherein the TOI is encoded by a nucleotide sequence having a cumulative human allele frequency from 1 to 10% and/or a total human genotype frequency from 1 to about 15% or from 1 to 15%.\",\n \"Clause 44: The method, ligand, composition, kit or use of any preceding clause wherein the TOI is a human TOI selected from Table 5; optionally for treating and/or preventing a corresponding disease or condition as set out in Table 5.For example, the TOI is human PCSK9, eg, a mature, cleaved, autocatalysed or active PCSK9.In an example, the disease is a cardiovascular disease such as hyperlipidaemia.\",\n \"Ligands of the invention are useful, for instance, in specific binding assays, for genotyping or phenotyping humans, affinity purification of the TOI and in screening assays to identify other antagonists of TOI activity.\",\n \"Some of the ligands of the invention are useful for inhibiting binding of TOI to a congnate human receptor or protein, or inhibiting TOI-mediated activities.\",\n \"The invention encompasses anti-TOI (eg, PCSK9) antibody ligands having a modified glycosylation pattern.\",\n \"In some applications, modification to remove undesirable glycosylation sites may be useful, or e.g., removal of a fucose moiety to increase antibody dependent cellular cytotoxicity (ADCC) function (see Shield et al.\",\n \"(2002) JBC 277:26733).\",\n \"In other applications, modification of galactosylation can be made in order to modify complement dependent cytotoxicity (CDC).\",\n \"In an example, the invention features a pharmaceutical composition comprising a ligand of the invention, wherein the ligand is or comprises a recombinant human antibody or fragment thereof which specifically binds the TOI (eg, a rare variant as described herein) and a pharmaceutically acceptable carrier.\",\n \"In one embodiment, the invention features a composition which is a combination of an antibody ligand or antigen-binding fragment of an antibody of the invention, and a second therapeutic agent.\",\n \"The second therapeutic agent may be any of an anti-inflammatory agent, an anti-angiogenesis agent, a painkiller, a diuretic, a chemotherapeutic agent, an anti-neoplastic agent, a vasodilator, a vasoconstrictor, a statin, a beta blocker, a nutrient, an adjuvant, an anti-obesity agent and an anti-diabetes agent.\",\n \"“Pharmaceutically acceptable” refers to approved or approvable by a regulatory agency of the USA Federal or a state government or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in animals, including humans.\",\n \"A “pharmaceutically acceptable carrier, excipient, or adjuvant” refers to an carrier, excipient, or adjuvant that can be administered to a subject, together with an agent, e.g., any antibody or antibody chain described herein, and which does not destroy the pharmacological activity thereof and is nontoxic when administered in doses sufficient to deliver a therapeutic amount of the agent.\",\n \"In an example, the invention features a method for inhibiting TOI activity using the anti-TOI ligand of the invention (eg, an antibody or antigen-binding portion of the antibody of the invention), wherein the therapeutic method comprises administering a therapeutically effective amount of a pharmaceutical composition comprising the ligand.\",\n \"The disorder treated is any disease or condition which is improved, ameliorated, inhibited or prevented by removal, inhibition or reduction of TOI activity.\",\n \"By the phrase “therapeutically effective amount” is meant an amount that produces the desired effect for which it is administered.\",\n \"The exact amount will depend on the purpose of the treatment, and will be ascertainable by one skilled in the art using known techniques (see, for example, Lloyd (1999) The Art, Science and Technology of Pharmaceutical Compounding).\",\n \"The term “specifically binds,” or the like, means that a ligand, eg, an antibody or antigen-binding fragment thereof, forms a complex with an antigen that is relatively stable under physiologic conditions.\",\n \"Specific binding can be characterized by an equilibrium dissociation constant of at least about 1×10−6 M or less (e.g., a smaller KD denotes a tighter binding).\",\n \"Methods for determining whether two molecules specifically bind are well known in the art and include, for example, equilibrium dialysis, surface plasmon resonance, and the like.\",\n \"An isolated antibody that specifically binds a human TOI may, however, exhibit cross-reactivity to other antigens such as a TOI molecule from another species.\",\n \"Moreover, multi-specific antibodies (e.g., bispecifics) that bind to human TOI and one or more additional antigens are nonetheless considered antibodies that “specifically bind” TOI, as used herein.\",\n \"Genotyping & Phenotyping The skilled person will be familiar with techniques that can be used for accurate genotyping and application to the invention.\",\n \"These include the following.\",\n \"1 Hybridization-based methods 1.1 Dynamic allele-specific hybridization 1.2 Molecular beacons 1.3 SNP microarrays 2 Enzyme-based methods 2.1 Restriction fragment length polymorphism 2.2 PCR-based methods 2.3 Flap endonuclease 2.4 Primer extension 2.5 5′-nuclease 2.6 Oligonucleotide Ligation Assay 3 Other post-amplification methods based on physical properties of DNA 3.1 Single strand conformation polymorphism 3.2 Temperature gradient gel electrophoresis 3.3 Denaturing high performance liquid chromatography 3.4 High-resolution melting of the entire amplicon 3.5 Use of DNA mismatch-binding proteins 3.6 SNPlex (SNPlex™ is a proprietary genotyping platform sold by Applied Biosystems).\",\n \"Next-generation sequencing technologies such as pyrosequencing is also useful.\",\n \"Reference is also made to GB2444410A and the genotyping method disclosed therein, which is incorporated herein by reference in its entirety.\",\n \"Miniaturized assays, such as microarrays with oligonucleotide reagents immobilized on small surfaces, are frequently proposed for large-scale mutation analysis and high-throughput genotyping (Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome (Wang D G, Fan J B, Siao C J, Berno A, Young P, Sapolsky R, Ghandour G, Perkins N, Winchester E, Spencer J, Kruglyak L, Stein L, Hsie L, Topaloglou T, Hubbell E, Robinson E, Mittmann M, Morris M S, Shen N, Kilburn D, Rioux J, Nusbaum C, Rozen S, Hudson T J, Lipshutz R, Chee M, Lander E S, Science.\",\n \"1998 May 15; 280(5366): 1077-82).\",\n \"Other high-throughput methods discriminate alleles by differential hybridization, primer extension, ligation and cleavage of an allele-specific probe (Review Accessing genetic variation: genotyping single nucleotide polymorphisms, Syvainen A C, Nat Rev Genet.\",\n \"2001 December; 2(12):930-42; Review Techniques patents for SNP genotyping, Twyman R M, Primrose S B, Pharmacogenomics.\",\n \"2003 January; 4(1):67-79).\",\n \"An approach for a fully automated, large-scale SNP analysis is the ‘homogeneous’ assay, i.e.\",\n \"a single-phase assay without separation steps, permitting continual monitoring during amplification.\",\n \"The TaqMan™ assay (Applied Biosystems), originally designed for quantitative real-time PCR, is a homogeneous, single-step assay also used in determination of mutation status of DNA (see, eg, A.\",\n \"A. Komar (ed.\",\n \"), Single Nucleotide Polymorphisms, Methods in Molecular Biology 578, DOI 10.1007/978-1-60327-411-1_19, Humana Press, a part of Springer Science+Business Media, LLC; and Single Nucleotide Polymorphisms, Methods in Molecular Biology™ Volume 578, 2009, pp 293-306, The TaqMan Method for SNP Genotyping, Gong-Qing Shen et al).\",\n \"The TaqMan SNP Genotyping Assay exploits the 5′-exonuclease activity of AmpliTaq Gold™ DNA polymerase to cleave a doubly labeled probe hybridized to the SNP-containing sequence of ssDNA.\",\n \"Cleavage separates a 5′-fluorophore from a 3′-quencher leading to detectable fluorescent signal.\",\n \"The use of two allele-specific probes carrying different fluorophores permits SNP determination in the same tube without any post-PCR processing.\",\n \"Genotype is determined from the ratio of intensities of the two fluorescent probes at the end of amplification.\",\n \"Thus, rather than taking advantage of the full set of real-time PCR data as in quantitative studies, only end-point data are used.\",\n \"TaqMan SNP genotyping in a high-throughput, automated manner is facilitated by the use of validated Pre-made TaqMan® Genotyping assays, but Custom TaqMan® Assays may also be used (High-throughput genotyping with single nucleotide polymorphisms, Ranade K, Chang M S, Ting C T, Pei D, Hsiao C F, Olivier M, Pesich R, Hebert J, Chen Y D, Dzau V J, Curb D, Olshen R, Risch N, Cox D R, Botstein D, Genome Res.\",\n \"2001 July; 11(7): 1262-8; Assessment of two flexible and compatible SNP genotyping platforms: TaqMan SNP Genotyping Assays and the SNPlex Genotyping System, De la Vega F M, Lazaruk K D, Rhodes M D, Wenz M H, Mutat Res.\",\n \"2005 Jun.\",\n \"3; 573(1-2): 111-35).\",\n \"The results of the assay can be automatically determined by genotyping software provided with real-time thermal cyclers (e.g.\",\n \"IQ software of Bio-Rad, Sequence Detection Software of Applied Biosystems).\",\n \"Single nucleotide polymorphisms (SNPs) can be determined using TaqMan™ real-time PCR assays (Applied Biosystems) and commercial software that assigns genotypes based on reporter probe signals at the end of amplification.\",\n \"An algorithm for automatic genotype calling of SNPs using the full course of TaqMan real-time data is available for use (A. Callegaro et al, Nucleic Acids Res.\",\n \"2006; 34(7): e56, Published online 2006 Apr.\",\n \"14.doi: 10.1093/nar/gk1185, PMCID: PMC1440877).\",\n \"The algorithm is unique in that it classifies samples according to the behavior of blanks (no DNA samples), which cluster with heterozygous samples.\",\n \"This method of classification eliminates the need for positive controls and permits accurate genotyping even in the absence of a genotype class, for example when one allele is rare.\",\n \"The skilled person will be familiar with techniques that can be used for accurate phenotyping and application to the invention.\",\n \"These include the use of amino acid sequencing of isolated target protein and comparison of sequences from different variants (eg, with the most common variant).\",\n \"An antibody that specifically and selectively binds in the area of a SNP under stringent conditions can also be used to identify a particular variant.\",\n \"In another method, the genotype is determined and a corresponding amino acid sequence (phenotype) determined, eg, by in silico translation.\",\n \"Therapeutic Administration and Formulations The invention provides therapeutic compositions comprising the anti-TOI ligand, eg, antibodies or antigen-binding fragments thereof, of the present invention.\",\n \"The administration of therapeutic compositions in accordance with the invention will be administered with suitable carriers, excipients, and other agents that are incorporated into formulations to provide improved transfer, delivery, tolerance, and the like.\",\n \"A multitude of appropriate formulations can be found in the formulary known to all pharmaceutical chemists: Remington's Pharmaceutical Sciences, Mack Publishing Company, Easton, Pa.\",\n \"These formulations include, for example, powders, pastes, ointments, jellies, waxes, oils, lipids, lipid (cationic or anionic) containing vesicles (such as LIPOFECTINT™), DNA conjugates, anhydrous absorption pastes, oil-in-water and water-in-oil emulsions, emulsions carbowax (polyethylene glycols of various molecular weights), semi-solid gels, and semi-solid mixtures containing carbowax.\",\n \"See also Powell et al.\",\n \"“Compendium of excipients for parenteral formulations” PDA (1998) J Pharm Sci Technol 52:238-311.The dose may vary depending upon the age and the size of a subject to be administered, target disease, conditions, route of administration, and the like.\",\n \"When the ligand, eg, antibody, of the present invention is used for treating various conditions and diseases associated with the TOI in an adult patient, it is advantageous to intravenously administer the antibody of the present invention normally at a single dose of about 0.01 to about 20 mg/kg body weight, more preferably about 0.02 to about 7, about 0.03 to about 5, or about 0.05 to about 3 mg/kg body weight.\",\n \"Depending on the severity of the condition, the frequency and the duration of the treatment can be adjusted.\",\n \"Various delivery systems are known and can be used to administer the ligand or pharmaceutical composition of the invention, for example a ligand provided by e.g., encapsulation in liposomes, microparticles, microcapsules, recombinant cells capable of expressing the mutant viruses, receptor mediated endocytosis (see, e.g., Wu et al.\",\n \"(1987) J. Biol.\",\n \"Chem.\",\n \"262:4429-4432).\",\n \"Methods of introduction include, but are not limited to, intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal, epidural, and oral routes.\",\n \"The ligand or composition may be administered by any convenient route, for example by infusion or bolus injection, by absorption through epithelial or mucocutaneous linings (e.g., oral mucosa, rectal and intestinal mucosa, etc.)\",\n \"and may be administered together with other biologically active agents.\",\n \"Administration can be systemic or local.\",\n \"The ligand or pharmaceutical composition can be also delivered in a vesicle, in particular a liposome (see Langer (1990) Science 249:1527-1533; Treat et al.\",\n \"(1989) in Liposomes in the Therapy of Infectious Disease and Cancer, Lopez Berestein and Fidler (eds.\",\n \"), Liss, New York, pp.\",\n \"353-365; Lopez-Berestein, ibid., pp.\",\n \"317-327; see generally ibid.).\",\n \"In certain situations, the ligand or pharmaceutical composition can be delivered in a controlled release system.\",\n \"In one embodiment, a pump may be used (see Langer, supra; Sefton (1987) CRC Crit.\",\n \"Ref.\",\n \"Biomed.\",\n \"Eng.\",\n \"14:201).\",\n \"In another embodiment, polymeric materials can be used; see, Medical Applications of Controlled Release, Langer and Wise (eds.\",\n \"), CRC Pres., Boca Raton, Fla. (1974).\",\n \"In yet another embodiment, a controlled release system can be placed in proximity of the composition's target, thus requiring only a fraction of the systemic dose (see, e.g., Goodson, in Medical Applications of Controlled Release, supra, vol.\",\n \"2, pp.\",\n \"115-138, 1984).\",\n \"The injectable preparations may include dosage forms for intravenous, subcutaneous, intracutaneous and intramuscular injections, drip infusions, etc.\",\n \"These injectable preparations may be prepared by methods publicly known.\",\n \"For example, the injectable preparations may be prepared, e.g., by dissolving, suspending or emulsifying the antibody or its salt described above in a sterile aqueous medium or an oily medium conventionally used for injections.\",\n \"As the aqueous medium for injections, there are, for example, physiological saline, an isotonic solution containing glucose and other auxiliary agents, etc., which may be used in combination with an appropriate solubilizing agent such as an alcohol (e.g., ethanol), a polyalcohol (e.g., propylene glycol, polyethylene glycol), a nonionic surfactant [e.g., polysorbate 80, HCO-50 (polyoxyethylene (50 mol) adduct of hydrogenated castor oil)], etc.\",\n \"As the oily medium, there are employed, e.g., sesame oil, soybean oil, etc., which may be used in combination with a solubilizing agent such as benzyl benzoate, benzyl alcohol, etc.\",\n \"The injection thus prepared is preferably filled in an appropriate ampoule.\",\n \"A pharmaceutical composition of the present invention can be delivered subcutaneously or intravenously with a standard needle and syringe.\",\n \"In addition, with respect to subcutaneous delivery, a pen delivery device readily has applications in delivering a pharmaceutical composition of the present invention.\",\n \"Such a pen delivery device can be reusable or disposable.\",\n \"A reusable pen delivery device generally utilizes a replaceable cartridge that contains a pharmaceutical composition.\",\n \"Once all of the pharmaceutical composition within the cartridge has been administered and the cartridge is empty, the empty cartridge can readily be discarded and replaced with a new cartridge that contains the pharmaceutical composition.\",\n \"The pen delivery device can then be reused.\",\n \"In a disposable pen delivery device, there is no replaceable cartridge.\",\n \"Rather, the disposable pen delivery device comes prefilled with the pharmaceutical composition held in a reservoir within the device.\",\n \"Once the reservoir is emptied of the pharmaceutical composition, the entire device is discarded.\",\n \"Numerous reusable pen and autoinjector delivery devices have applications in the subcutaneous delivery of a ligand or pharmaceutical composition of the present invention.\",\n \"Examples include, but certainly are not limited to AUTOPEN™ (Owen Mumford, Inc., Woodstock, UK), DISETRONIC™ pen (Disetronic Medical Systems, Burghdorf, Switzerland), HUMALOG MIX 75/25™ pen, HUMALOG™ pen, HUMALIN 70/30™ pen (Eli Lilly and Co., Indianapolis, Ind.\",\n \"), NOVOPEN™ I, II and III (Novo Nordisk, Copenhagen, Denmark), NOVOPEN JUNIOR™ (Novo Nordisk, Copenhagen, Denmark), BD™ pen (Becton Dickinson, Franklin Lakes, N.J.), OPTIPENT™, OPTIPEN PRO™, OPTIPEN STARLET™, and OPTICLIKT™ (sanofi-aventis, Frankfurt, Germany), to name only a few.\",\n \"Examples of disposable pen delivery devices having applications in subcutaneous delivery of a pharmaceutical composition of the present invention include, but certainly are not limited to the SOLOSTAR™ pen (sanofi-aventis), the FLEXPEN™ (Novo Nordisk), and the KWIKPEN™ (Eli Lilly).\",\n \"Advantageously, the pharmaceutical compositions for oral or parenteral use described above are prepared into dosage forms in a unit dose suited to fit a dose of the ligand(s).\",\n \"Such dosage forms in a unit dose include, for example, tablets, pills, capsules, injections (ampoules), suppositories, etc.\",\n \"The amount of the aforesaid antibody contained is generally about 5 to about 500 mg per dosage form in a unit dose; especially in the form of injection, it is preferred that the aforesaid antibody is contained in about 5 to about 100 mg and in about 10 to about 250 mg for the other dosage forms.\",\n \"Exemplary TOIs For example in any configuration, aspect, concept, example or configuration of the invention, the or each TOI is selected from the group consisting of ABCF1; ACVR1; ACVR1B; ACVR2; ACVR2B; ACVRL1; ADORA2A; Aggrecan; AGR2; AICDA; AW1; AIG1; AKAP1; AKAP2; AIYIH; amyloid-beta; AMHR2; ANGPT1; ANGPT2; ANGPTL3; ANGPTL4; ANPEP; APC; APOC1; AR; Axl; AZGP1 (zinc-a-glycoprotein); B7.1; B7.2; BAD; BAFF; BAG1; BAI1; BCL2; BCL6; BDNF; BLNK; BLR1 (MDR15); BlyS; BMP1; BMP2; BMP3B (GDF1O); BMP4; BMP6; BMP8; BMPR1A; BMPR1B; BMPR2; BPAG1 (plectin); BRCA1; C19orflO (IL27w); C3; C4A; C5; C5R1; CANT1; CASP1; CASP4; CAV1; CB1; CCBP2 (D6/JAB61); CCL1 (I-309); CCL11 (eotaxin); CCL13 (MCP-4); CCL15 (MIP-id); CCL16 (HCC-4); CCL17 (TARC); CCL18 (PARC); CCL19 (MIP-3b); CCL2 (MCP-1); MCAF; CCL2O (MIP-3a); CCL21 (MIP-2); SLC; exodus-2; CCL22 (MDC/STC-1); CCL23 (MPIF-1); CCL24 (MPIF-2 I eotaxin-2); CCL25 (TECK); CCL26 (eotaxin-3); CCL27 (CTACK/ILC); CCL28; CCL3 (MIP-1a); CCL4 (MIP-1b); CCL5 (RANTES); CCL7 (MCP-3); CCL8 (mcp-2); CCNA1; CCNA2; CCND1; CCNE1; CCNE2; CCR1 (CKR1/HM145); CCR2 (mcp-1RB/RA); CCR3 (CKR3/CMKBR3); CCR4; CCR5 (CMKBR5/ChemR13); CCR6 (CMKBR6/CKR-L3/STRL22/DRY6); CCR7 (CKR7/EBI1); CCR8 (CMKBR8/TER1/CKR-L1); CCR9 (GPR-9-6); CCRL1 (VSHK1); CCRL2 (L-CCR); CD7, CD164; CD19; CD1C; CD20; CD200; CD-22; CD24; CD28; CD3; CD37; CD38; CD3E; CD3G; CD3Z; CD4; CD40; CD40L; CD44; CD45RB; CD52; CD69; CD72; CD74; CD79A; CD79B; CD8; CD8O; CD81; CD83; CD86; CD96; CD207; CDH1 (E-cadherin); CDH10; CDH12; CDH13; CDH18; CDH19; CDH20; CDH5; CDH7; CDH8; CDH9; CDK2; CDK3; CDK4; CDK5; CDK6; CDK7; CDK9; CDKN1A (p21Wap1/Cip1); CDKN1B (p27Kip1); CDKNIC; CDKN2A (p161NK4a); CDKN2B; CDKN2C; CDKN3; CEBPB; CELSR3; CER1; CHGA; CHGB; Chitinase; CHRNG; CHST10; CKLFSF2; CKLFSF3; CKLFSF4; CKLFSF5; CKLFSF6; CKLFSF7; CKLFSF8; CLDN3; CLDN7 (claudin-7); CLN3; CLU (clusterin); CMKLR1; CMKOR1 (RDC1); CNR1; COL18A1; COL1A1; COL4A3; COL6A1; CR2; CRP; CSF1 (M-CSF); CRLF2; CSF2 (GM-CSF); CSF3 (GCSF); CTLA4; CTNNB1 (b-catenin); CTSB (cathepsin B); CX3CL1 (SCYDi); CX3CR1 (V28); CXCR6; CXCL1 (GRO1); CXCL10 (IP-10); CXCL11 (I-TAC/IP-9); CXCL12 (SDF1); CXCL13; CXCL14; CXCL16; CXCL2 (GRO2); CXCL3 (GRO3); CXCL5 (ENA-78 I LIX); CXCL6 (GCP-2); CXCL9 (MIG); CXCR3 (GPR9/CKR-L2); CXCR4; CXCR6 (TYMSTR ISTRL33 I Bonzo); CYB5; CYC1; CYSLTR1; DAB2IP; DAND5; DES; DKFZp451J0118; DNCL1; DPP4; E2F1; ECGF1; EDG1; EFNAI; EFNA3; EFNB2; EGF; EGFR; ELAC2; ENG; ENO1; ENO2; ENO3; EphA4; EPHB4; EPO; ERBB2 (Her-2); EREG; ERK8; ESR1; ESR2; F3 (TF); FADD; FasL; FASN; FCER1A; FCER2; FCGR3A; FCRL4; FGF; FGF1 (aFGF); FGF10; FGF11; FGF12; FGF12B; FGF13; FGF14; FGF16; FGF17; FGF18; FGF19; FGF2 (bFGF); FGF20; FGF21; FGF22; FGF23; FGF3 (int-2); FGF4 (HST); FGF5; FGF6 (HST-2); FGF7 (KGF); FGF8; FGF9; FGFR3; FIGF (VEGFD); FIL1 (EPSILON); FIL1 (ZETA); FLJ12584; FLJ25530; FLRT1 (fibronectin); FLT1; FOS; FOSL1 (FRA-1); FY (DARC); GABRP (GABAa); GAGEB1; GAGEC1; Galectin-3; GALNAC4S-65T; GATA3; GDF5; GFI1; GGT1; GHR; GM-CSF; GNAS1; GNRH1; GPR2 (CCR1O); GPR31; GPR44; GPR81 (FKSG8O); GPR87; GPR137C; GRCC10 (C10); GRP; GSN (Gelsolin); GSTP1; HAVCR1; HAVCR2; HDAC4; EDAC5; HDAC7A; HDAC9; hepcidin; hemojuvelin; HGF; HIF1A; HIP1; histamine and histamine receptors; HLA-A; HLA-DRA; HM74; HMOX1; HUMCYT2A; ICEBERG; ICOS; 1D2; IFN-a; IFNA1; IFNA2; IFNA4; IFNA5; IFNA6; IFNA7; IFNB1; IFNgamma; TFNW1; IGBP1; IGF1; IGF1R; IGF2; IGFBP2; IGFBP3; IGFBP6; IL-1; IL10; IL10RA; IL10RB; IL11; IL11RA; IL-12; IL12A; IL12B; IL12RB1; IL12RB2; 1L13; IL13RA1; IL13RA2; 1L14; 1L15; IL15RA; IL16; 1L17; IL17B; IL17C; IL17R; 1L18; IL18BP; IL18R1; IL18RAP; 1L19; IL1A; IL1B; IL1F10; IL1F5; IL1F6; IL1F7; IL1F8; IL1F9; IL1HY1; IL1R1; IL1R2; IL1RAP; IL1RAPL1; IL1RAPL2; IL1RL1; IL1RL2 IL1RN; 1L2; 1L20; IL20RA; IL21R; 1L22; 1L22R; 1L22RA2; 1L23; 1L24; 1L25; 1L26; 1L27; 1L28A; 1L28B; 1L29; IL2RA; IL2RB; IL2RG; 1L3; 1L30; IL3RA; 1L4; IL4R; 1L5; IL5RA; 1L6; IL6 receptor; IL6ST (glycoprotein 130); 1L7; TL7R; 1L8; IL8RA; IL8RB; IL8RB; 1L9; IL9R; ILK; INHA; INHBA; INSL3; INSL4; IRAK1; IRAK2; ITGA1; ITGA2; 1TGA3; ITGA6 (a6 integrin); ITGAV; ITGB3; ITGB4 (b 4 integrin); JAG1; JAK1; JAK3; JUN; K6HF; KAI1; KDR; MTLG; KLF5 (GC Box BP); KLF6; KLK10; KLK12; KLK13; KLK14; KLK15; KLK3; KLK4; KLK5; KLK6; KLK9; KRT1; KRT19 (Keratin 19); KRT2A; KRTHB6 (hair-specific type II keratin); LAG3; LAMA5; LEP (leptin); LIGHT; Lingo-p75; Lingo-Troy; LPS; LRP5; LTA (TNF-b); LTB; LTB4R (GPR16); LTB4R2; LTBR; MACMARCKS; MAG or Omgp; MAP2K7 (c-Jun); MDK; MIB1; midkine; MIF; MIP-2; MK167 (Ki-67); MMP2; MMP9; MS4A1; MSMB; MT3 (metallothionectin-ifi); MTSS 1; MUC 1 (mucin); MYC; MYD88; NCK2; neurocan; Nav1.7; Nav1.8; NFKB1; NFKB2; NGFB (NGF); NGFR; NgR-Lingo; NgR-Nogo66 (Nogo); NgR-p75; NgR-Troy; NME1 (NM23A); NOX5; NPPB; NROB1; NROB2; NR1D1; NR1D2; NR1H2; NR1H3; NR1H4; NR1I2; NR1I3; NR2C1; NR2C2; NR2E1; NR2E3; NR2F1; NR2F2; NR2F6; NR3C1; NR3C2; NR4A1; NR4A2; NR4A3; NR5A1; NR5A2; NR6A1; NRP1; NRP2; NT5E; NTN4; ODZ1; OPG; OPRD1; OX40L; OX40; P2RX7; PAP; PART1; PATE; PAWR; PCA3; PCNA; PCSK9, PD-1, PD-L1; PDGFA; PDGFB; PECAM1; PF4 (CXCL4); PGF; PGR; phosphacan; PIAS2; Placental Growth Factor (PIGF); PIK3CG; PLAU (uPA); PLG; PLXDC1; PPBP (CXCL7); PPID; PR1; PRKCQ; PRKD1; PRL; PROC; PROK2; PSAP; PSCA; PTAFR; PTEN; PTGS2 (COX-2); PTN; RAC2 (p21Rac2); RARB; RGS1; RGS13; RGS3; RNF110 (ZNF144); ROBO2; ROR1; S100A2; SCGB1D2 (lipophilin B); SCGB2A1 (mammaglobin 2); SCGB2A2 (mammaglobin 1); SCYE1 (endothelial Monocyte-activating cytokine); SDF2; SERPINA1; SERPINIA3; SERPINB5 (maspin); SERPINE1 (PAT-i); SERPINF1; SHBG; SLA2; SLC2A2; SLC33A1; SLC43A1; SLIT2; SPP1; SPRR1B (Spri); ST6GAL1; STAB1; STAT6; STEAP; STEAP2; TB4R2; TBX21; TCP1O; TDGF1; TEK; TGFA; TGFB1; TGFBII1; TGFB2; TGFB3; TGFBI; TGFBR1; TGFBR2; TGFBR3; TH1L; THBS1 (thrombospondin-1); THBS2; THBS4; THPO; TIE (Tie-i); TIM3; TMP3; tissue factor; TLR1O; TLR2; TLR3; TLR4; TLR5; TLR6; TLR7; TLR8; TLR9; TMPRSS6; TNF; TNF-a; TNFAIP2 (B94); TNFAIP3; TNFRSF1 1A; TNFRSF1A; TNFRSFiB; TNFRSF21; TNFRSF5; TNFRSF6 (Fas); TNFRSF7; TNFRSF8; TNFRSF9; TNFSF1O (TRAIL); TNFSF1 1 (TRANCE); TNFSF12 (APO3L); TNFSF13 (April); TNFSF13B; TNFSF14 (HVEM-L); TNFSF1 5 (VEGI); TNFSF1 8; TNFSF4 (0X40 ligand); TNFSF5 (CD4O ligand); TNFSF6 (FasL); TNFSF7 (CD27 ligand); TNFSF8 (CD3O ligand); TNFSF9 (4-1BB ligand); TOLLIP; Toll-like receptors; TOP2A (topoisomerase lia); TP53; TPM1; TPM2; TRADD; TRAF1; TRAF2; TRAF3; TRAF4; TRAF5; TRAF6; TRAIL; TREM1; TREM2; TRPC6; TSLP; TWEAK; VEGFA; VEGFB; VEGFC; versican; VHL C5; VLA-4; Wnt7A; XCL1 (lymphotactin); XCL2 (SCM-lb); XCR1 (GPR5/CCXCR1); YY1; and ZFPM2.In an example, the TOI is a human TOI selected from Table 5.In an example, the TOI is OX40 ligand.\",\n \"In an example, the TOI is OX40.In an example, the TOI is PCSK9.In an example, the TOI is IL6 receptor (IL-6R).\",\n \"In an example, the TOI is LIGHT.\",\n \"In an example, the TOI is VEGF-A.\",\n \"In an example, the TOI is TNF alpha.\",\n \"In an example, the TOI is PIGF.\",\n \"In an example, the TOI is IGF1R.\",\n \"In an example, the TOI is OPG.\",\n \"In an example, the TOI is ICOS In an example, the TOI is NGF.\",\n \"In an example, the TOI is BMP6.In an example, the TOI is ferroportin.\",\n \"In an example, the TOI is TMPRSS6.In an example, the TOI is hemojuvelin.\",\n \"In an example, the TOI is VEGF receptor.\",\n \"In an example, the TOI is PDGF receptor.\",\n \"In an example, the TOI is stem cell factor receptor.\",\n \"In an example, the TOI is hepcidin.\",\n \"In an example, the TOI is IL-4 receptor alpha.\",\n \"In an example, the TOI is sclerostin.\",\n \"In an example, the TOI is IL-13 receptor.\",\n \"In an example, the TOI is CD7.In an example, the TOI is delta-like ligand-4 (Dll4).\",\n \"In an example, the TOI is HGF.\",\n \"In an example, the TOI is angiopoietin-2 (Ang2).\",\n \"In an example, the TOI is GDF8.In an example, the TOI is ERBB3.In an example, the TOI is IL-17 receptor.\",\n \"In an example, the TOI is CD40.In an example, the TOI is CD40 ligand.\",\n \"In an example, the TOI is EGFR.\",\n \"For convenience, the meaning of some terms and phrases used in the specification, examples, and appended claims, are provided below.\",\n \"Unless stated otherwise, or implicit from context, the following terms and phrases include the meanings provided below.\",\n \"The definitions are provided to aid in describing particular embodiments, and are not intended to limit the claimed invention, because the scope of the invention is limited only by the claims.\",\n \"Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.\",\n \"If there is an apparent discrepancy between the usage of a term in the art and its definition provided herein, the definition provided within the specification shall prevail.\",\n \"For convenience, certain terms employed herein, in the specification, examples and appended claims are collected here.\",\n \"The terms “decrease”, “reduced”, or “reduction” are all used herein to mean a decrease by a statistically significant amount.\",\n \"In some embodiments, “reduce,” “reduction” or “decrease” typically means a decrease by at least 10% as compared to a reference level (e.g.\",\n \"the absence of a given treatment) and can include, for example, a decrease by at least about 10%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, or more.\",\n \"As used herein, “reduction” does not encompass a complete reduction as compared to a reference level.\",\n \"A decrease can be preferably down to a level accepted as within the range of normal for an individual without a given disorder.\",\n \"However, for example, for the purposes of lowering or reducing cholesterol level, for example, a reduction by about 5-10 points can be considered a “decrease” or “reduction.” In certain aspects of all embodiments of the invention, the term “inhibition” is used.\",\n \"Inhibition refers and refers to decrease by at least 10% as compared to a reference level (e.g.\",\n \"the absence of a given treatment) and can include, for example, a decrease by at least about 10%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 98%, at least about 99%, or more including 100% inhibition as compared to a reference level.\",\n \"“Complete inhibition” refers to a 100% inhibition as compared to a reference level.\",\n \"The terms “increased”, “increase”, “enhance”, or “activate” are all used herein to mean an increase by a statically significant amount.\",\n \"In some embodiments, the terms “increased”, “increase”, “enhance”, or “activate” can mean an increase of at least 10% as compared to a reference level, for example an increase of at least about 20%, or at least about 30%, or at least about 40%, or at least about 50%, or at least about 60%, or at least about 70%, or at least about 80%, or at least about 90% or up to and including a 100% increase or any increase between 10-100% as compared to a reference level, or at least about a 2-fold, or at least about a 3-fold, or at least about a 4-fold, or at least about a 5-fold or at least about a 10-fold increase, or any increase between 2-fold and 10-fold or greater as compared to a reference level.\",\n \"In the context of a marker or symptom, an “increase” is a statistically significant increase in such level.\",\n \"As used herein, the term “substantially” refers to the qualitative condition of exhibiting total or near-total extent or degree of a characteristic or property of interest.\",\n \"One of ordinary skill in the biological arts will understand that biological and chemical phenomena rarely, if ever, go to completion and/or proceed to completeness or achieve or avoid an absolute result.\",\n \"The term “substantially” is therefore used herein to capture the potential lack of completeness inherent in many biological and chemical phenomena.\",\n \"For the removal of doubt, “substantially” can refer to at least a 90% extent or degree of a characteristic or property of interest, e.g.\",\n \"at least 90%, at least 92%, at least 95%, at least 98%, at least 99% or greater.\",\n \"As used herein, a “subject” means a human or animal.\",\n \"Usually the animal is a vertebrate such as a primate, rodent, domestic animal or game animal.\",\n \"Primates include chimpanzees, cynomologous monkeys, spider monkeys, and macaques, e.g., Rhesus.\",\n \"Rodents include mice, rats, woodchucks, ferrets, rabbits and hamsters.\",\n \"In some embodiments, the subject is a mammal, e.g., a primate, e.g., a human.\",\n \"The terms, “individual,” “patient” and “subject” are used interchangeably herein.\",\n \"In some embodiments, the subject can be a non-human vertebrate, e.g.\",\n \"a primate, a rodent, a mouse, a rat, a pig, a sheep, a zebrafish, a frog, etc.\",\n \"Preferably, the subject is a mammal.\",\n \"The mammal can be a human, non-human primate, mouse, rat, dog, cat, horse, or cow, but is not limited to these examples.\",\n \"Mammals other than humans can be advantageously used as subjects that represent animal models of a disease or condition, e.g., a cardiovascular condition.\",\n \"A subject can be male or female.\",\n \"A subject can be one who has been previously diagnosed with or identified as suffering from or having a condition in need of treatment or one or more complications related to such a condition, and optionally, have already undergone treatment for the condition or the one or more complications related to the condition.\",\n \"Alternatively, a subject can also be one who has not been previously diagnosed as having the condition or one or more complications related to the condition.\",\n \"For example, a subject can be one who exhibits one or more risk factors for the condition or one or more complications related to the condition or a subject who does not exhibit risk factors.\",\n \"A “subject in need” or “human in need” of treatment for a particular condition can be a subject having that condition, such as increased cholesterol levels, diagnosed as having that condition, or at risk of developing that condition.\",\n \"As used herein, the terms “protein” and “polypeptide” are used interchangeably herein to designate a series of amino acid residues, connected to each other by peptide bonds between the alpha-amino and carboxy groups of adjacent residues.\",\n \"The terms “protein”, and “polypeptide” refer to a polymer of amino acids with natural amino acids.\",\n \"When referring to “modified polypeptides” one refers to polypeptides that include modified amino acids (e.g., phosphorylated, glycated, glycosylated, etc.)\",\n \"and amino acid analogs, regardless of its size or function.\",\n \"“Protein” and “polypeptide” are often used in reference to relatively large polypeptides, whereas the term “peptide” is often used in reference to small polypeptides, but usage of these terms in the art overlaps.\",\n \"The terms “protein” and “polypeptide” are used interchangeably herein when referring to a gene product and fragments thereof.\",\n \"Thus, exemplary polypeptides or proteins include gene products, naturally occurring proteins with the specified sequence.\",\n \"One can also use peptide homologs, peptide orthologs, peptide paralogs, peptide fragments and other equivalents, variants, fragments, and analogs of the peptides as these terms are understood by one of ordinary skill in the art.\",\n \"As used herein, the term “nucleic acid” or “nucleic acid sequence” refers to any molecule, preferably a polymeric molecule, incorporating units of ribonucleic acid, deoxyribonucleic acid.\",\n \"The nucleic acid can be either single-stranded or double-stranded.\",\n \"A single-stranded nucleic acid can be one nucleic acid strand of a denatured double-stranded DNA.\",\n \"Alternatively, it can be a single-stranded nucleic acid not derived from any double-stranded DNA.\",\n \"In one aspect, the nucleic acid can be DNA.\",\n \"In another aspect, the nucleic acid can be RNA.\",\n \"Suitable nucleic acid molecules are DNA, including genomic DNA or cDNA.\",\n \"Other suitable nucleic acid molecules are RNA, including mRNA.\",\n \"In some aspects one can also use analogs of nucleic acids.\",\n \"As used herein, the term “nucleic acid probe” refers to an isolated oligonucleotide molecule having a nucleic acid sequence which can hybridize to a target nucleic acid sequence, e.g.\",\n \"specifically hybridize to the target sequence.\",\n \"In some embodiments, a nucleic acid probe can further comprise a detectable label.\",\n \"In some embodiments, a nucleic acid probe can be attached to a solid surface.\",\n \"In some embodiments, a nucleic acid from is from about 5 nt to about 100 nt in length.\",\n \"As used herein, the term “siRNA” refers to a nucleic acid that forms an RNA molecule comprising two individual strands of RNA which are substantially complementary to each other.\",\n \"Typically, the siRNA is at least about 15-40 nucleotides in length (e.g., each complementary sequence of the double stranded siRNA is about 15-40 nucleotides in length, and the double stranded siRNA is about 15-40 base pairs in length, preferably about 19-25 base nucleotides, e.g., 19, 20, 21, 22, 23, 24, or 25 nucleotides in length).\",\n \"In some embodiments, a siRNA can be blunt-ended.\",\n \"In some embodiments, a siRNA can comprise a 3′ and/or 5′ overhang on each strand having a length of about 0, 1, 2, 3, 4, or 5 nucleotides.\",\n \"The length of the overhang is independent between the two strands, i.e., the length of the overhang on one strand is not dependent on the length of the overhang on the second strand.\",\n \"The siRNA molecules can also comprise a 3′ hydroxyl group.\",\n \"In some embodiments, the siRNA can comprise a 5′ phosphate group.\",\n \"A siRNA has the ability to reduce or inhibit expression of a gene or target RNA when the siRNA is present or expressed in the same cell as the target gene, e.g.\",\n \"the target RNA.\",\n \"siRNA-dependent post-transcriptional silencing of gene expression involves cutting the target RNA molecule at a site guided by the siRNA.\",\n \"As used herein, “PCSK9” or “proprotein convertase subtilisin/kexin type 9” refers to a serine protease involved in regulating the levels of the low density lipoprotein receptor (LDLR) protein (Horton et al., 2007; Seidah and Prat, 2007).\",\n \"PCSK9 has been shown to directly interact with the LDLR protein, be endocytosed along with the LDLR, and co-immunofluoresce with the LDLR throughout the endosomal pathway (Lagace et al., 2006).\",\n \"PCSK9 is a prohormone-proprotein convertase in the subtilisin (S8) family of serine proteases (Seidah et al., 2003).\",\n \"The sequence of PCSK9 for a variety of species is known, e.g., human PCSK9 (NCBI Gene ID No: 255738).\",\n \"Nucleotide and polypeptide sequences for a number of PCSK9 isoforms are provided herein, e.g., SEQ ID NOs: 1-37.PCSK9 exists as both a pro-form and a mature form.\",\n \"Autocatalysis of the PCSK9 proform occurs between Gln152 and Ser153 (VFAQ|SIP (SEQ ID NO: 67)) (Naureckiene et al., 2003), and has been shown to be required for its secretion from cells (Seidah et al., 2003).\",\n \"The inactive form prior to this cleavage can be referred to herein as the “inactive”, “pro-form”, or “unprocessed” form of PCSK9.The C-terminal fragment generated by the autocatalysis event can be referred to herein as the “mature,” “cleaved”, “processed” or “active” PCSK9.Examples of pro-form and mature PCSK9 isoforms are provided herein, see, e.g.\",\n \"SEQ ID NOs: 1-27.As used herein, the “catalytic domain” of PCSK9 refers to the portion of a PCSK9 polypeptide corresponding to positions 153 to 449 of PCSK9, e.g.\",\n \"of SEQ ID NO: 1.As used herein, the “C-terminal domain” of PCSK9 refers to the portion of a PCSK9 polypeptide corresponding to positions 450-692 of PCSK9, e.g., of SEQ ID NO: 1.As used herein, a disease or condition “mediated by PCSK9” refers to a disease or condition which is caused by or characterized by a change in PCSK9, e.g.\",\n \"a change in expression level, a change in activity, and/or the presence of a variant or mutation of PCSK9.Non-limiting examples of such diseases or conditions can include, for example, a lipid disorder, hyperlipoproteinemia, hyperlipidemia; dyslipidemia; hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication, type II diabetes, high blood pressure, and a cardiovascular disease or condition.\",\n \"In an example, the disease or condition is an inflammatory or autoimmune disease or condition.\",\n \"Methods of identifying and/or diagnosing such diseases and conditions are well known to medical practitioners of ordinary skill.\",\n \"A subject at risk of having or developing a disease or condition mediated by PCSK9 can be a subject exhibiting one or more signs or symptoms of such a disease or condition or having one or more risk factors for such a disease or condition, e.g.\",\n \"being overweight, having elevated cholesterol level, comprising one or more genetic polymorphisms known to predispose to the disease or condition, e.g., elevated cholesterol level, such as having a mutation in the LDLR (encoding low-density lipoprotein receptor) or APOB (encoding apolipoprotein B) or in the PCSK9 gene and/or having a family history of such a disease or condition.\",\n \"As used herein, “ligand” refers to a molecule which can bind, e.g., specifically bind, to a second molecule or receptor.\",\n \"In some embodiments, a ligand can be, e.g., an antibody, antibody fragment, antibody portion, and/or affibody.\",\n \"The term “variant” as used herein refers to a peptide or nucleic acid that differs from the polypeptide or nucleic acid (eg, the most common one in humans, eg, most frequent in a database as disclosed herein, such as the 1000 Genomes Project database) by one or more amino acid or nucleic acid deletions, additions, yet retains one or more specific functions or biological activities of the naturally occurring molecule.\",\n \"Amino acid substitutions include alterations in which an amino acid is replaced with a different naturally-occurring amino acid residue.\",\n \"Such substitutions may be classified as “conservative”, in which case an amino acid residue contained in a polypeptide is replaced with another naturally occurring amino acid of similar character either in relation to polarity, side chain functionality or size.\",\n \"Such conservative substitutions are well known in the art.\",\n \"Substitutions encompassed by the present invention may also be “non-conservative”, in which an amino acid residue which is present in a peptide is substituted with an amino acid having different properties, such as naturally-occurring amino acid from a different group (e.g., substituting a charged or hydrophobic amino; acid with alanine), or alternatively, in which a naturally-occurring amino acid is substituted with a non-conventional amino acid.\",\n \"In some embodiments amino acid substitutions are conservative.\",\n \"Also encompassed within the term variant when used with reference to a polynucleotide or polypeptide, refers to a polynucleotide or polypeptide that can vary in primary, secondary, or tertiary structure, as compared to a reference polynucleotide or polypeptide, respectively (e.g., as compared to a wild-type polynucleotide or polypeptide).\",\n \"Variants of PCSK9 are provided elsewhere herein.\",\n \"Variants of PCSK9 can include the forms described herein as a, f, c, r, p, m, e h, aj, and q. Sequences of these variants are provided herein, see, e.g, SEQ ID NOs: 1-27 and in Table 1, 2 or 6.In some aspects, one can use “synthetic variants”, “recombinant variants”, or “chemically modified” polynucleotide variants or polypeptide variants isolated or generated using methods well known in the art.\",\n \"“Modified variants” can include conservative or non-conservative amino acid changes, as described below.\",\n \"Polynucleotide changes can result in amino acid substitutions, additions, deletions, fusions and truncations in the polypeptide encoded by the reference sequence.\",\n \"Some aspects use include insertion variants, deletion variants or substituted variants with substitutions of amino acids, including insertions and substitutions of amino acids and other molecules) that do not normally occur in the peptide sequence that is the basis of the variant, for example but not limited to insertion of ornithine which do not normally occur in human proteins.\",\n \"The term “conservative substitution,” when describing a polypeptide, refers to a change in the amino acid composition of the polypeptide that does not substantially alter the polypeptide's activity.\",\n \"For example, a conservative substitution refers to substituting an amino acid residue for a different amino acid residue that has similar chemical properties.\",\n \"Conservative amino acid substitutions include replacement of a leucine with an isoleucine or valine, an aspartate with a glutamate, or a threonine with a serine.\",\n \"“Conservative amino acid substitutions” result from replacing one amino acid with another having similar structural and/or chemical properties, such as the replacement of a leucine with an isoleucine or valine, an aspartate with a glutamate, or a threonine with a serine.\",\n \"Thus, a “conservative substitution” of a particular amino acid sequence refers to substitution of those amino acids that are not critical for polypeptide activity or substitution of amino acids with other amino acids having similar properties (e.g., acidic, basic, positively or negatively charged, polar or non-polar, etc.)\",\n \"such that the substitution of even critical amino acids does not reduce the activity of the peptide, (i.e.\",\n \"the ability of the peptide to penetrate the blood brain barrier (BBB)).\",\n \"Conservative substitution tables providing functionally similar amino acids are well known in the art.\",\n \"For example, the following six groups each contain amino acids that are conservative substitutions for one another: 1) Alanine (A), Serine (S), Threonine (T); 2) Aspartic acid (D), Glutamic acid (E); 3) Asparagine (N), Glutamine (Q); 4) Arginine (R), Lysine (K); 5) Isoleucine (I), Leucine (L), Methionine (M), Valine (V); and 6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W).\",\n \"(See also Creighton, Proteins, W. H. Freeman and Company (1984), incorporated by reference in its entirety.)\",\n \"In some embodiments, individual substitutions, deletions or additions that alter, add or delete a single amino acid or a small percentage of amino acids can also be considered “conservative substitutions” if the change does not reduce the activity of the peptide.\",\n \"Insertions or deletions are typically in the range of about 1 to 5 amino acids.\",\n \"The choice of conservative amino acids may be selected based on the location of the amino acid to be substituted in the peptide, for example if the amino acid is on the exterior of the peptide and expose to solvents, or on the interior and not exposed to solvents.\",\n \"In alternative embodiments, one can select the amino acid which will substitute an existing amino acid based on the location of the existing amino acid, i.e.\",\n \"its exposure to solvents (i.e.\",\n \"if the amino acid is exposed to solvents or is present on the outer surface of the peptide or polypeptide as compared to internally localized amino acids not exposed to solvents).\",\n \"Selection of such conservative amino acid substitutions are well known in the art, for example as disclosed in Dordo et al, J. Mol Biol, 1999, 217, 721-739 and Taylor et al, J. Theor.\",\n \"Biol.\",\n \"119(1986); 205-218 and S. French and B. Robson, J. Mol.\",\n \"Evol.\",\n \"19(1983)171.Accordingly, one can select conservative amino acid substitutions suitable for amino acids on the exterior of a protein or peptide (i.e.\",\n \"amino acids exposed to a solvent), for example, but not limited to, the following substitutions can be used: substitution of Y with F, T with S or K, P with A, E with D or Q, N with D or G, R with K, G with N or A, T with S or K, D with N or E, I with L or V, F with Y, S with T or A, R with K, G with N or A, K with R, A with S, K or P. In alternative embodiments, one can also select conservative amino acid substitutions encompassed suitable for amino acids on the interior of a protein or peptide, for example one can use suitable conservative substitutions for amino acids is on the interior of a protein or peptide (i.e.\",\n \"the amino acids are not exposed to a solvent), for example but not limited to, one can use the following conservative substitutions: where Y is substituted with F, T with A or S, I with L or V, W with Y, M with L, N with D, G with A, T with A or S, D with N, I with L or V, F with Y or L, S with A or T and A with S, G, T or V. In some embodiments, non-conservative amino acid substitutions are also encompassed within the term of variants.\",\n \"As used herein an “antibody” refers to IgG, IgM, IgA, IgD or IgE molecules or antigen-specific antibody fragments thereof (including, but not limited to, a Fab, F(ab′)2, Fv, disulphide linked Fv, scFv, single domain antibody, closed conformation multispecific antibody, disulphide-linked scfv, diabody), whether derived from any species that naturally produces an antibody, or created by recombinant DNA technology; whether isolated from serum, B-cells, hybridomas, transfectomas, yeast or bacteria.\",\n \"Antibodies can be humanized using routine technology.\",\n \"As described herein, an “antigen” is a molecule that is bound by a binding site on an antibody agent.\",\n \"Typically, antigens are bound by antibody ligands and are capable of raising an antibody response in vivo.\",\n \"An antigen can be a polypeptide, protein, nucleic acid or other molecule or portion thereof.\",\n \"The term “antigenic determinant” refers to an epitope on the antigen recognized by an antigen-binding molecule, and more particularly, by the antigen-binding site of said molecule.\",\n \"As used herein, the term “antibody fragment” refers to a polypeptide that includes at least one immunoglobulin variable domain or immunoglobulin variable domain sequence and which specifically binds a given antigen.\",\n \"An antibody fragment can comprise an antibody or a polypeptide comprising an antigen-binding domain of an antibody.\",\n \"In some embodiments, an antibody fragment can comprise a monoclonal antibody or a polypeptide comprising an antigen-binding domain of a monoclonal antibody.\",\n \"For example, an antibody can include a heavy (H) chain variable region (abbreviated herein as VH), and a light (L) chain variable region (abbreviated herein as VL).\",\n \"In another example, an antibody includes two heavy (H) chain variable regions and two light (L) chain variable regions.\",\n \"The term “antibody fragment” encompasses antigen-binding fragments of antibodies (e.g., single chain antibodies, Fab and sFab fragments, F(ab′)2, Fd fragments, Fv fragments, scFv, and domain antibodies (dAb) fragments (see, e.g.\",\n \"de Wildt et al., Eur J. Immunol.\",\n \"1996; 26(3):629-39; which is incorporated by reference herein in its entirety)) as well as complete antibodies.\",\n \"An antibody can have the structural features of IgA, IgG, IgE, IgD, IgM (as well as subtypes and combinations thereof).\",\n \"Antibodies can be from any source, including mouse, rabbit, pig, rat, and primate (human and non-human primate) and primatized antibodies.\",\n \"Antibodies also include midibodies, humanized antibodies, chimeric antibodies, and the like.\",\n \"As used herein, “antibody variable domain” refers to the portions of the light and heavy chains of antibody molecules that include amino acid sequences of Complementarity Determining Regions (CDRs; ie., CDR1, CDR2, and CDR3), and Framework Regions (FRs).\",\n \"VH refers to the variable domain of the heavy chain.\",\n \"VL refers to the variable domain of the light chain.\",\n \"According to the methods used in this invention, the amino acid positions assigned to CDRs and FRs may be defined according to Kabat (Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, Md., 1987 and 1991)) or according to IMGT nomenclature.\",\n \"D domain or region refers to the diversity domain or region of an antibody chain.\",\n \"J domain or region refers to the joining domain or region of an antibody chain.\",\n \"An antibody “gene segment”, e.g.\",\n \"a VH gene segment, D gene segment, or JH gene segment refers to oligonucleotide having a nucleic acid sequence that encodes that portion of an antibody, e.g.\",\n \"a VH gene segment is an oligonucleotide comprising a nucleic acid sequence that encodes a polypeptide VH domain.\",\n \"The VH and VL regions can be further subdivided into regions of hypervariability, termed “complementarity determining regions” (“CDR”), interspersed with regions that are more conserved, termed “framework regions” (“FR”).\",\n \"The extent of the framework region and CDRs has been precisely defined (see, IMGT or Kabat, E. A., et al.\",\n \"(1991) Sequences of Proteins of Immunological Interest, Fifth Edition, U.S. Department of Health and Human Services, NIH Publication No.\",\n \"91-3242, and Chothia, C. et al.\",\n \"(1987) J. Mol.\",\n \"Biol.\",\n \"196:901-917; which are incorporated by reference herein in their entireties).\",\n \"Each VH and VL is typically composed of three CDRs and four FRs, arranged from amino-terminus to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4.The terms “antigen-binding fragment” or “antigen-binding domain”, which are used interchangeably herein are used to refer to one or more fragments of a full length antibody that retain the ability to specifically bind to a target of interest.\",\n \"Examples of binding fragments encompassed within the term “antigen-binding fragment” of a full length antibody include (i) a Fab fragment, a monovalent fragment consisting of the VL, VH, CL and CH1 domains; (ii) a F(ab′)2 fragment, a bivalent fragment including two Fab fragments linked by a disulfide bridge at the hinge region; (iii) an Fd fragment consisting of the VH and CH1 domains; (iv) an Fv fragment consisting of the VL and VH domains of a single arm of an antibody, (v) a dAb fragment (Ward et al., (1989) Nature 341:544-546; which is incorporated by reference herein in its entirety), which consists of a VH or VL domain; and (vi) an isolated complementarity determining region (CDR) that retains specific antigen-binding functionality.\",\n \"As used herein, the term “antibody binding site” refers to a polypeptide or domain that comprises one or more CDRs of an antibody and is capable of binding an antigen.\",\n \"For example, the polypeptide comprises a CDR3 (eg, HCDR3).\",\n \"For example the polypeptide comprises CDRs 1 and 2 (eg, HCDR1 and 2) or CDRs 1-3 of a variable domain of an antibody (eg, HCDRs1-3).\",\n \"In an example, the antibody binding site is provided by a single variable domain (eg, a VH or VL domain).\",\n \"In another example, the binding site comprises a VH/VL pair or two or more of such pairs.\",\n \"As used herein, the term “specific binding” refers to a chemical interaction between two molecules, compounds, cells and/or particles wherein the first entity binds to the second, target entity with greater specificity and affinity than it binds to a third entity which is a non-target.\",\n \"For example, in an diagnostic test the specific binding of a ligand can distinguish between two variant PCSK9 proteins as described herein.\",\n \"In some embodiments, specific binding can refer to an affinity of the first entity for the second target entity which is at least 10 times, at least 50 times, at least 100 times, at least 500 times, at least 1000 times or greater than the affinity for the third nontarget entity.\",\n \"In the context of oligonucleotide strands which interact via hybridization, specific binding can be “specific hybridization.” Additionally, and as described herein, a recombinant human(ized) antibody can be further optimized to decrease potential immunogenicity, while maintaining functional activity, for therapy in humans.\",\n \"In this regard, functional activity means a polypeptide capable of displaying one or more known functional activities associated with a recombinant antibody or antibody reagent thereof as described herein.\",\n \"Such functional activities include, e.g.\",\n \"the ability to bind to a target molecule.\",\n \"The term “immunizing” refers to the step or steps of administering one or more antigens to an animal so that antibodies can be raised in the animal Generally, immunizing comprises injecting the antigen or antigens into the animal.\",\n \"Immunization can involve one or more administrations of the antigen or antigens.\",\n \"Suitable methods are prime-boost and RIMMS procedures as known to the skilled person in the art.\",\n \"As used herein, an “affibody” refers to a relatively small synthetic protein molecule that has high binding affinity for a target protein (e.g.\",\n \"for PCSK9 or a variant therefo).\",\n \"Affibodies are composed of a three-helix bundle domain derived from the IgG-binding domain of staphylococcal protein A.\",\n \"The protein domain consists of a 58 amino acid sequence, with 13 randomized amino acids affording a range of affibody variants.\",\n \"Despite being significantly smaller than an antibody (an affibody weighs about 6 kDa while an antibody commonly weighs about 150 kDa), an affibody molecule works like an antibody since its binding site is approximately equivalent in surface area to the binding site of an antibody.\",\n \"As used herein, “VH3-23*04” refers to a human VH domain variant comprising the polypeptide sequence of SEQ ID NO: 38.As opposed to the reference sequence, VH3-23*04 has a valine residue instead of a leucine residue (see FIGS.\",\n \"3 and 4; L24V, numbering including signal sequence; valine at position 5 shown in FIG.\",\n \"4) as a result of the presence of the rs56069819 SNP in the nucleic acid sequence encoding the VH domain.\",\n \"As used herein, “rs56069819” refers to a mutation or variant in a VH gene segment from adenosine to cytosine (or thymine to guanine, depending upon the strand of DNA which is being read), resulting in the VH domain encoding VH3-23*04.Rs56069819 is depicted in FIG.\",\n \"4 and SEQ ID NO: 39, which demonstrate the T->G mutation (it is noted that the dbSNP entry for RS5606819 depicts the other strand, which comprises the A->C mutation).\",\n \"Further description of VH3-23*04 can be found, e.g., in US Patent Publication 2013/0071405; which is incorporated by reference herein in its entirety.\",\n \"As used herein, “determine” or “determining” refers to ascertaining, e.g., by a quantitative or qualitative analysis.\",\n \"As used herein, “has been determined” can refer to ascertaining on the basis of previously obtained information or simultaneously obtained information.\",\n \"In some aspects of all embodiments of the invention selecting can include automation such as a computer implemented software program that upon input of the relevant data such as ethnicity or a panel of SNP data can make the determination based on the instructions set forth herein.\",\n \"As used herein, “assaying” refers to assessing, evaluating, quantifying, measuring, or characterizing an analyte, e.g., measuring the level of an analyte in a sample, identifying an analyte, or detecting the presence or absence of an analyte in a sample.\",\n \"In some embodiments, assaying refers to detecting a presence or absence of the analyte of interest.\",\n \"In some embodiments, assaying refers to quantifying an amount of an analyte, e.g., providing a measure of concentration or degree of analyte abundance.\",\n \"In some embodiments, assaying refers to enumerating the number of molecules of analyte present in a sample and/or specimen, e.g., to determine an analyte copy number.\",\n \"As used herein “multiplex” refers to the carrying out of a method or process simultaneously and in the same reaction vessel on two or more, typically three or more, different target sequences, e.g.\",\n \"on two or more isoforms of PCSK9, or PCSK9 and an additional target.\",\n \"A multiplex analysis typically includes analysis of 10-50: 10-100; 10-1000, 10-5000, 10-10000 reactions in a multiplex format, such as a multiwall, an array, or a multichannel reaction.\",\n \"Often the analysis or multiplex analysis is also automated using robotics and typically software executed by a computer and may include a robotic handling of samples, automatic or robotic selection of positive or negative results, assaying for presence of absence of a target, such as a nucleic acid polymorphism or a protein variant.\",\n \"The term “biological sample” or “test sample” as used herein denotes a sample taken or isolated from a biological organism, e.g., a sample from a subject.\",\n \"Exemplary biological samples include, but are not limited to, a biofluid sample; serum; plasma; urine; saliva; hair, epithelial cells, skin, a tumor biopsy and/or tissue sample etc.\",\n \"The term also includes a mixture of the above-mentioned samples.\",\n \"The term “test sample” or “biological sample” also includes untreated or pretreated (or pre-processed) biological samples.\",\n \"For the analysis of nucleic acids, the biological sample should typically comprise at least one cell comprising nucleic acids.\",\n \"The test sample can be obtained by removing a sample of cells from a subject, but can also be accomplished by using previously isolated cells (e.g.\",\n \"isolated at a prior time point and isolated by the same or another person).\",\n \"In addition, the test sample can be freshly collected or a previously collected, refrigerated, frozen or otherwise preserved sample.\",\n \"In some embodiments, the test sample can be an untreated test sample.\",\n \"As used herein, the phrase “untreated test sample” refers to a test sample that has not had any prior sample pre-treatment except for dilution and/or suspension in a solution.\",\n \"Exemplary methods for treating a test sample include, but are not limited to, centrifugation, filtration, sonication, homogenization, heating, freezing and thawing, and combinations thereof.\",\n \"In some embodiments, the test sample can be a frozen test sample, e.g., a frozen tissue.\",\n \"The frozen sample can be thawed before employing methods, assays and systems described herein.\",\n \"After thawing, a frozen sample can be centrifuged before being subjected to methods, assays and systems described herein.\",\n \"In some embodiments, the test sample is a clarified test sample, for example, by centrifugation and collection of a supernatant comprising the clarified test sample.\",\n \"In some embodiments, a test sample can be a pre-processed test sample, for example, supernatant or filtrate resulting from a treatment selected from the group consisting of centrifugation, filtration, thawing, purification, and any combinations thereof.\",\n \"In some embodiments, the test sample can be treated with a chemical and/or biological reagent.\",\n \"Chemical and/or biological reagents can be employed to protect and/or maintain the stability of the sample, including biomolecules (e.g., nucleic acid and protein) therein, during processing.\",\n \"One exemplary reagent is a protease inhibitor, which is generally used to protect or maintain the stability of protein during processing.\",\n \"The skilled artisan is well aware of methods and processes appropriate for pre-processing of biological samples required for determination of the level of an expression product as described herein.\",\n \"As used herein, “genotyping” refers to a process of determining the specific allelic composition of a cell and/or subject at one or more position within the genome, e.g.\",\n \"by determining the nucleic acid sequence at that position.\",\n \"Genotyping refers to a nucleic acid analysis and/or analysis at the nucleic acid level.\",\n \"As used herein, “phenotyping” refers a process of determining the identity and/or composition of an expression product of a cell and/or subject, e.g.\",\n \"by determining the polypeptide sequence of an expression product.\",\n \"Phenotyping refers to a protein analysis and/or analysis at the protein level.\",\n \"As used herein, the term “nucleic acid amplification” refers to the production of additional copies of a nucleic acid sequence and is typically carried out using polymerase chain reaction (PCR) or ligase chain reaction (LCR) technologies well known in the art (Dieffenbach, C. W. and G. S. Dveksler (1995) PCR Primer, a Laboratory Manual, Cold Spring Harbor Press, Plainview, N.Y.).\",\n \"Other methods for amplification are also contemplated in aspects of the invention.\",\n \"The term “allele-specific amplification” refers to a reaction (e.g., PCR reaction) in which at least one of the primers (e.g., allele-specific primer) is chosen from a polymorphic area of gene (e.g., single nucleotide polymorphism), with the polymorphism located at or near the primer's 3′-end.\",\n \"A mismatched primer will not initiate amplification, whereas a matched primer will initiate amplification.\",\n \"The appearance of an amplification product is indicative of the presence of the polymorphism.\",\n \"As used herein, “sequencing” refers to the determination of the exact order of nucleotide bases in a strand of DNA (deoxyribonucleic acid) or RNA (ribonucleic acid) or the exact order of amino acids residues or peptides in a protein.\",\n \"Nucleic acid sequencing can be done using Sanger sequencing or next-generation high-throughput sequencing.\",\n \"As used herein “next-generation sequencing” refers to oligonucleotide sequencing technologies that have the capacity to sequence oligonucleotides at speeds above those possible with conventional sequencing methods (e.g.\",\n \"Sanger sequencing), due to performing and reading out thousands to millions of sequencing reactions in parallel.\",\n \"Non-limiting examples of next-generation sequencing methods/platforms include Massively Parallel Signature Sequencing (Lynx Therapeutics); 454 pyro-sequencing (454 Life Sciences/Roche Diagnostics); solid-phase, reversible dye-terminator sequencing (Solexa/Illumina): SOLiD technology (Applied Biosystems); Ion semiconductor sequencing (ION Torrent); DNA nanoball sequencing (Complete Genomics); and technologies available from Pacific Biosciences, Intelligen Bio-systems, Oxford Nanopore Technologies, and Helicos Biosciences.\",\n \"Next-generation sequencing technologies and the constraints and design parameters of associated sequencing primers are well known in the art (see, e.g.\",\n \"Shendure, et al., “Next-generation DNA sequencing,” Nature, 2008, vol.\",\n \"26, No.\",\n \"10, 1135-1145; Mardis, “The impact of next-generation sequencing technology on genetics,” Trends in Genetics, 2007, vol.\",\n \"24, No.\",\n \"3, pp.\",\n \"133-141; Su, et al., “Next-generation sequencing and its applications in molecular diagnostics” Expert Rev Mol Diagn, 2011, 11(3):333-43; Zhang et al., “The impact of next-generation sequencing on genomics”, J Genet Genomics, 2011, 38(3):95-109; (Nyren, P. et al.\",\n \"Anal Biochem 208: 17175 (1993); Bentley, D. R. Curr Opin Genet Dev 16:545-52 (2006); Strausberg, R. L., et al.\",\n \"Drug Disc Today 13:569-77 (2008); U.S. Pat.\",\n \"No.\",\n \"7,282,337; U.S. Pat.\",\n \"No.\",\n \"7,279,563; U.S. Pat.\",\n \"No.\",\n \"7,226,720; U.S. Pat.\",\n \"No.\",\n \"7,220,549; U.S. Pat.\",\n \"No.\",\n \"7,169,560; U.S. Pat.\",\n \"No.\",\n \"6,818,395; U.S. Pat.\",\n \"No.\",\n \"6,911,345; US Pub.\",\n \"Nos.\",\n \"2006/0252077; 2007/0070349; and 20070070349; which are incorporated by reference herein in their entireties).\",\n \"As used herein, “nucleic acid hybridization” refers to the pairing of complementary RNA and DNA strands as well as the pairing of complementary DNA single strands.\",\n \"In some embodiments, nucleic acid hybridization can refer to a method of determining a nucleic acid sequence and/or identity by hybridizing a nucleic acid sample with a probe, e.g.\",\n \"Northern or Southern blot analysis or microarray analysis.\",\n \"As used herein, the terms “treat,” “treatment,” “treating,” or “amelioration” refer to therapeutic treatments, wherein the object is to reverse, alleviate, ameliorate, inhibit, slow down or stop the progression or severity of a condition associated with a disease or disorder.\",\n \"The term “treating” includes reducing or alleviating at least one adverse effect or symptom of a condition, disease or disorder.\",\n \"Treatment is generally “effective” if one or more symptoms or clinical markers are reduced.\",\n \"Alternatively, treatment is “effective” if the progression of a disease is reduced or halted.\",\n \"That is, “treatment” includes not just the improvement of symptoms or markers, but also a cessation of, or at least slowing of, progress or worsening of symptoms compared to what would be expected in the absence of treatment.\",\n \"Beneficial or desired clinical results include, but are not limited to, alleviation of one or more symptom(s), diminishment of extent of disease, stabilized (i.e., not worsening) state of disease, delay or slowing of disease progression, amelioration or palliation of the disease state, remission (whether partial or total), and/or decreased mortality, whether detectable or undetectable.\",\n \"The term “treatment” of a disease also includes providing relief from the symptoms or side-effects of the disease (including palliative treatment).\",\n \"For treatment to be effective a complete cure is not contemplated.\",\n \"The method can in certain aspects include cure as well.\",\n \"As used herein, the term “pharmaceutical composition” refers to the active agent in combination with a pharmaceutically acceptable carrier e.g.\",\n \"a carrier commonly used in the pharmaceutical industry.\",\n \"The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio.\",\n \"As used herein, the term “administering,” refers to the placement of a compound as disclosed herein into a subject by a method or route which results in at least partial delivery of the agent at a desired site.\",\n \"Pharmaceutical compositions comprising the compounds disclosed herein can be administered by any appropriate route which results in an effective treatment in the subject.\",\n \"Multiple compositions can be administered separately or simultaneously.\",\n \"Separate administration refers to the two compositions being administered at different times, e.g.\",\n \"at least 10, 20, 30, or 10-60 minutes apart, or 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12 hours apart.\",\n \"One can also administer compositions at 24 hours apart, or even longer apart.\",\n \"Alternatively, two or more compositions can be administered simultaneously, e.g.\",\n \"less than 10 or less than 5 minutes apart.\",\n \"Compositions administered simultaneously can, in some aspects, be administered as a mixture, with or without similar or different time release mechanism for each of the components.\",\n \"As used herein, “contacting” refers to any suitable means for delivering, or exposing, an agent to at least one complex, enzyme, or cell.\",\n \"Exemplary delivery methods include, but are not limited to, direct delivery to cell culture medium, perfusion, injection, or other delivery method well known to one skilled in the art.\",\n \"As used herein, “obtain” refers to any method of acquiring, securing, procuring, or coming into the possession of, e.g.\",\n \"a sample.\",\n \"Obtaining a biological sample from a subject can comprise physical removing a sample from a subject (e.g.\",\n \"drawing blood or taking a hair or saliva sample) without or without active participation from the subject; receiving a sample from a subject (e.g.\",\n \"the subject collects a saliva or hair sample themselves and provides it, e.g.\",\n \"in a container provided for the purpose); or procuring a sample from a storage facility, medical facility, or medical provider.\",\n \"Obtain from the human or subject, refers to an active step of, e.g., drawing blood or taking a tissue or cell sample.\",\n \"As used herein, “cholesterol level” refers to a level of one or more of total cholesterol, LDL cholesterol, HDL cholesterol, and/or triglycerides.\",\n \"Cholesterol levels can be the level of cholesterol in the blood of a subject.\",\n \"As used herein in reference to cholesterol levels, “maintain” refers to preventing the level from worsening (e.g.\",\n \"increasing).\",\n \"In some embodiments, maintaining a particular level refers to a process that results in the cholesterol level not increasing by more than 10% over time.\",\n \"Maintaining may also refer to maintaining a previously achieved level.\",\n \"For example, if a human has received statin treatment, one can maintain the cholesterol level achieved using the statin treatment.\",\n \"In some embodiments, the subject treated according to the methods described herein has previously had their cholesterol level reduced.\",\n \"As used herein, “previously reduced” indicates that at a prior point in time, the subject experienced a decrease in cholesterol levels.\",\n \"The decrease can be due to administration of a pharmaceutical composition (e.g.\",\n \"administration of a composition as described herein or another composition, e.g.\",\n \"a statin) or due to another cause, e.g.\",\n \"a change in diet and/or exercise.\",\n \"An existing treatment for high cholesterol levels is the administration of a statin.\",\n \"As referred to herein, a “statin” (also known as HMG-CoA reductase inhibitors) are inhibitors of the enzyme HMG-coA reductase, which mediates cholesterol production in the liver.\",\n \"Statins, by competitively binding HMG-CoA reductase, prevent the binding of HMG-CoA to the enzyme and thereby inhibit the activity of the reductase (e.g.\",\n \"the production of mevalonate).\",\n \"Non-limiting examples of statins can include atorvastatin (LIPITOR™), fluvastatin (LESCOL™), lovastatin (MEVACOR™, ALTOCOR™), pitavastatin (LIVALO™), pravastatin (PRAVACHOL™), rosuvastatin (CRESTOR™), and simvastatin (ZOCOR™).\",\n \"Statins can be administered in combination with other agents, e.g.\",\n \"the combination of ezetimibe and simvastatin.\",\n \"Some subjects are, or become, resistant to statin treatment.\",\n \"As used herein, “resistant to statin treatment” or “reduced responsiveness to statin treatment” refers to a subject exhibiting a statistically significantly lower response to the administration of a statin as compared to a reference level.\",\n \"The reference level can be, e.g., the average response for a population of subjects or the level of the individual subject at an earlier date.\",\n \"A response to statin treatment is readily measured by one of skill in the art, e.g., measurement of cholesterol levels, changes in cholesterol levels, and/or HMG-CoA reductase activity.\",\n \"As used herein, the term “detectable label” refers to a molecule or moiety that can be detected, e.g.\",\n \"measured and/or determined to be present or absent.\",\n \"Detectable labels can comprise, for example, a light-absorbing dye, a fluorescent dye, or a radioactive label.\",\n \"Detectable labels, methods of detecting them, and methods of incorporating them into reagents (e.g.\",\n \"antibodies and nucleic acid probes) are well known in the art.\",\n \"In some embodiments, detectable labels can include labels that can be detected by spectroscopic, photochemical, biochemical, immunochemical, electromagnetic, radiochemical, or chemical means, such as fluorescence, chemifluoresence, or chemiluminescence, or any other appropriate means.\",\n \"The detectable labels used in the methods described herein can be primary labels (where the label comprises a moiety that is directly detectable or that produces a directly detectable moiety) or secondary labels (where the detectable label binds to another moiety to produce a detectable signal, e.g., as is common in immunological labeling using secondary and tertiary antibodies).\",\n \"The detectable label can be linked by covalent or non-covalent means to the reagent.\",\n \"Alternatively, a detectable label can be linked such as by directly labeling a molecule that achieves binding to the reagent via a ligand-receptor binding pair arrangement or other such specific recognition molecules.\",\n \"Detectable labels can include, but are not limited to radioisotopes, bioluminescent compounds, chromophores, antibodies, chemiluminescent compounds, fluorescent compounds, metal chelates, and enzymes.\",\n \"In other embodiments, the detectable label can be a fluorescent compound.\",\n \"When the fluorescently label is exposed to light of the proper wavelength, its presence can then be detected due to fluorescence.\",\n \"In some embodiments, a detectable label can be a fluorescent dye molecule, or fluorophore including, but not limited to fluorescein, phycoerythrin, phycocyanin, o-phthaldehyde, fluorescamine, Cy3™, Cy5™, allophycocyanine, Texas Red, peridenin chlorophyll, cyanine, tandem conjugates such as phycoerythrin-Cy5™, green fluorescent protein, rhodamine, fluorescein isothiocyanate (FITC) and Oregon Green™, rhodamine and derivatives (e.g., Texas red and tetrarhodimine isothiocynate (TRITC)), biotin, phycoerythrin, AMCA, CyDyes™, 6-carboxyfhiorescein (commonly known by the abbreviations FAM and F), 6-carboxy-2′,4′,7′,4,7-hexachlorofiuorescein (HEX), 6-carboxy-4′,5′-dichloro-2′,7′-dimethoxyfiuorescein (JOE or J), N,N,N′,N′-tetramethyl-6carboxyrhodamine (TAMRA or T), 6-carboxy-X-rhodamine (ROX or R), 5-carboxyrhodamine-6G (R6G5 or G5), 6-carboxyrhodamine-6G (R6G6 or G6), and rhodamine 110; cyanine dyes, e.g.\",\n \"Cy3, Cy5 and Cy7 dyes; coumarins, e.g umbelliferone; benzimide dyes, e.g.\",\n \"Hoechst 33258; phenanthridine dyes, e.g.\",\n \"Texas Red; ethidium dyes; acridine dyes; carbazole dyes; phenoxazine dyes; porphyrin dyes; polymethine dyes, e.g.\",\n \"cyanine dyes such as Cy3, Cy5, etc; BODIPY dyes and quinoline dyes.\",\n \"In some embodiments, a detectable label can be a radiolabel including, but not limited to 3H, 125I, 35S, 14C, 32P, and 33P.\",\n \"In some embodiments, a detectable label can be an enzyme including, but not limited to horseradish peroxidase and alkaline phosphatase.\",\n \"An enzymatic label can produce, for example, a chemiluminescent signal, a color signal, or a fluorescent signal.\",\n \"Enzymes contemplated for use as a detectable label can include, but are not limited to, malate dehydrogenase, staphylococcal nuclease, delta-V-steroid isomerase, yeast alcohol dehydrogenase, alpha-glycerophosphate dehydrogenase, triose phosphate isomerase, horseradish peroxidase, alkaline phosphatase, asparaginase, glucose oxidase, beta-galactosidase, ribonuclease, urease, catalase, glucose-VI-phosphate dehydrogenase, glucoamylase and acetylcholinesterase.\",\n \"In some embodiments, a detectable label is a chemiluminescent label, including, but not limited to lucigenin, luminol, luciferin, isoluminol, theromatic acridinium ester, imidazole, acridinium salt and oxalate ester.\",\n \"In some embodiments, a detectable label can be a spectral colorimetric label including, but not limited to colloidal gold or colored glass or plastic (e.g., polystyrene, polypropylene, and latex) beads.\",\n \"In some embodiments, reagents can also be labeled with a detectable tag, such as c-Myc, HA, VSV-G, HSV, FLAG, V5, HIS, or biotin.\",\n \"Other detection systems can also be used, for example, a biotin-streptavidin system.\",\n \"In this system, the antibodies immunoreactive (i. e. specific for) with the biomarker of interest is biotinylated.\",\n \"Quantity of biotinylated antibody bound to the biomarker is determined using a streptavidin-peroxidase conjugate and a chromagenic substrate.\",\n \"Such streptavidin peroxidase detection kits are commercially available, e. g. from DAKO; Carpinteria, Calif. A reagent can also be detectably labeled using fluorescence emitting metals such as 152Eu, or others of the lanthanide series.\",\n \"These metals can be attached to the reagent using such metal chelating groups as diethylenetriaminepentaacetic acid (DTPA) or ethylenediaminetetraacetic acid (EDTA).\",\n \"As used herein, “authorization number” or “marketing authorization number” refers to a number issued by a regulatory agency upon that agency determining that a particular medical product and/or composition may be marketed and/or offered for sale in the area under the agency's jurisdiction.\",\n \"As used herein “regulatory agency” refers to one of the agencies responsible for evaluating, e.g, the safety and efficacy of a medical product and/or composition and controlling the sales/marketing of such products and/or compositions in a given area.\",\n \"The Food and Drug Administration (FDA) in the US and the European Medicines Agency (EPA) in Europe are but two examples of such regulatory agencies.\",\n \"Other non-limiting examples can include SDA, MPA, MHPRA, IMA, ANMAT, Hong Kong Department of Health-Drug Office, CDSCO, Medsafe, and KFDA.\",\n \"As used herein, “injection device” refers to a device that is designed for carrying out injections, an injection including the steps of temporarily fluidically coupling the injection device to a person's tissue, typically the subcutaneous tissue.\",\n \"An injection further includes administering an amount of liquid drug into the tissue and decoupling or removing the injection device from the tissue.\",\n \"In some embodiments, an injection device can be an intravenous device or IV device, which is a type of injection device used when the target tissue is the blood within the circulatory system, e.g., the blood in a vein.\",\n \"A common, but non-limiting example of an injection device is a needle and syringe.\",\n \"As used herein, a “buffer” refers to a chemical agent that is able to absorb a certain quantity of acid or base without undergoing a strong variation in pH.\",\n \"As used herein, “packaging” refers to how the components are organized and/or restrained into a unit fit for distribution and/or use.\",\n \"Packaging can include, e.g., boxes, bags, syringes, ampoules, vials, tubes, clamshell packaging, barriers and/or containers to maintain sterility, labeling, etc.\",\n \"As used herein, “instructions” refers to a display of written, printed or graphic matter on the immediate container of an article, for example the written material displayed on a vial containing a pharmaceutically active agent, or details on the composition and use of a product of interest included in a kit containing a composition of interest.\",\n \"Instructions set forth the method of the treatment as contemplated to be administered or performed.\",\n \"As used herein, a “solid surface” refers to an object suitable for the attachment of biomolecules.\",\n \"Non-limiting examples of a solid surface can include a particle (including, but not limited to an agarose or latex bead or particle or a magnetic particle), a bead, a nanoparticle, a polymer, a substrate, a slide, a coverslip, a plate, a dish, a well, a membrane, and/or a grating.\",\n \"The solid surface can include many different materials including, but not limited to, polymers, plastics, resins, polysaccharides, silicon or silica based materials, carbon, metals, inorganic glasses, and membranes.\",\n \"As used herein, “classification” of a subject, e.g., classification of the subject's ancestry refers to determining if the subject has biological ancestors who originated in a particular geographical area, and are therefore likely to have particular genetic variants found in the populations which have historically occupied that area.\",\n \"Classification can comprise, e.g.\",\n \"obtaining information on the subject's family, interviewing the subject or a family member regarding their biological family's ancestry, and/or genetic testing.\",\n \"Classification can be on the basis used for the 1000 Genomes Project, as will be familiar to the skilled person in the art.\",\n \"In some embodiments, the subject can be classified as being of a particular ancestry if at least the subject's genome comprises a substantial number of different alleles in common with other humans of that ancestry (eg, determined by reference to the 1000 Genomes Project database), for example, at least 10, 20, 30, 40, 50 or 100 or more alleles in common.\",\n \"Abbreviations for particular ancestral groups are provided in Table 4.The term “statistically significant” or “significantly” refers to statistical significance and generally means a two standard deviation (2SD) or greater difference.\",\n \"Other than in the operating examples, or where otherwise indicated, all numbers expressing quantities of ingredients or reaction conditions used herein should be understood as modified in all instances by the term “about.” The term “about” when used in connection with percentages can mean±1%.\",\n \"As used herein the term “comprising” or “comprises” is used in reference to compositions, methods, and respective component(s) thereof, that are essential to the method or composition, yet open to the inclusion of unspecified elements, whether essential or not.\",\n \"The term “consisting of” refers to compositions, methods, and respective components thereof as described herein, which are exclusive of any element not recited in that description of the embodiment.\",\n \"As used herein the term “consisting essentially of” refers to those elements required for a given embodiment.\",\n \"The term permits the presence of elements that do not materially affect the basic and novel or functional characteristic(s) of that embodiment.\",\n \"The singular terms “a,” “an,” and “the” include plural referents unless context clearly indicates otherwise.\",\n \"Similarly, the word “or” is intended to include “and” unless the context clearly indicates otherwise.\",\n \"Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of this disclosure, suitable methods and materials are described below.\",\n \"The abbreviation, “e.g.” is derived from the Latin exempli gratia, and is used herein to indicate a non-limiting example.\",\n \"Thus, the abbreviation “e.g.” is synonymous with the term “for example.” Definitions of common terms in cell biology and molecular biology can be found in “The Merck Manual of Diagnosis and Therapy”, 19th Edition, published by Merck Research Laboratories, 2006 (ISBN 0-911910-19-0); Robert S. Porter et al.\",\n \"(eds.\",\n \"), The Encyclopedia of Molecular Biology, published by Blackwell Science Ltd., 1994 (ISBN 0-632-02182-9); Benjamin Lewin, Genes X, published by Jones & Bartlett Publishing, 2009 (ISBN-10: 0763766321); Kendrew et al.\",\n \"(eds.\",\n \"), Molecular Biology and Biotechnology: a Comprehensive Desk Reference, published by VCH Publishers, Inc., 1995 (ISBN 1-56081-569-8) and Current Protocols in Protein Sciences 2009, Wiley Intersciences, Coligan et al., eds.\",\n \"Unless otherwise stated, the present invention was performed using standard procedures, as described, for example in Sambrook et al., Molecular Cloning: A Laboratory Manual (4 ed.\",\n \"), Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., USA (2012); Davis et al., Basic Methods in Molecular Biology, Elsevier Science Publishing, Inc., New York, USA (1995); or Methods in Enzymology: Guide to Molecular Cloning Techniques Vol.\",\n \"152, S. L. Berger and A. R. Kimmel Eds., Academic Press Inc., San Diego, USA (1987); Current Protocols in Protein Science (CPPS) (John E. Coligan, et.\",\n \"al., ed., John Wiley and Sons, Inc.), Current Protocols in Cell Biology (CPCB) (Juan S. Bonifacino et. al.\",\n \"ed., John Wiley and Sons, Inc.), and Culture of Animal Cells: A Manual of Basic Technique by R. Ian Freshney, Publisher: Wiley-Liss; 5th edition (2005), Animal Cell Culture Methods (Methods in Cell Biology, Vol.\",\n \"57, Jennie P. Mather and David Barnes editors, Academic Press, 1st edition, 1998) which are all incorporated by reference herein in their entireties.\",\n \"Other terms are defined herein within the description of the various aspects of the invention.\",\n \"All patents and other publications; including literature references, issued patents, published patent applications, and co-pending patent applications; cited throughout this application are expressly incorporated herein by reference for the purpose of describing and disclosing, for example, the methodologies described in such publications that might be used in connection with the technology described herein.\",\n \"These publications are provided solely for their disclosure prior to the filing date of the present application.\",\n \"Nothing in this regard should be construed as an admission that the inventors are not entitled to antedate such disclosure by virtue of prior invention or for any other reason.\",\n \"All statements as to the date or representation as to the contents of these documents is based on the information available to the applicants and does not constitute any admission as to the correctness of the dates or contents of these documents.\",\n \"The description of embodiments of the disclosure is not intended to be exhaustive or to limit the disclosure to the precise form disclosed.\",\n \"While specific embodiments of, and examples for, the disclosure are described herein for illustrative purposes, various equivalent modifications are possible within the scope of the disclosure, as those skilled in the relevant art will recognize.\",\n \"For example, while method steps or functions are presented in a given order, alternative embodiments may perform functions in a different order, or functions may be performed substantially concurrently.\",\n \"The teachings of the disclosure provided herein can be applied to other procedures or methods as appropriate.\",\n \"The various embodiments described herein can be combined to provide further embodiments.\",\n \"Aspects of the disclosure can be modified, if necessary, to employ the compositions, functions and concepts of the above references and application to provide yet further embodiments of the disclosure.\",\n \"Moreover, due to biological functional equivalency considerations, some changes can be made in protein structure without affecting the biological or chemical action in kind or amount.\",\n \"These and other changes can be made to the disclosure in light of the detailed description.\",\n \"All such modifications are intended to be included within the scope of the appended claims.\",\n \"Specific elements of any of the foregoing embodiments can be combined or substituted for elements in other embodiments.\",\n \"Furthermore, while advantages associated with certain embodiments of the disclosure have been described in the context of these embodiments, other embodiments may also exhibit such advantages, and not all embodiments need necessarily exhibit such advantages to fall within the scope of the disclosure.\",\n \"It will be understood that particular configurations, aspects, examples, clauses and embodiments described herein are shown by way of illustration and not as limitations of the invention.\",\n \"The principal features of this invention can be employed in various embodiments without departing from the scope of the invention.\",\n \"Those skilled in the art will recognize, or be able to ascertain using no more than routine study, numerous equivalents to the specific procedures described herein.\",\n \"Such equivalents are considered to be within the scope of this invention and are covered by the claims.\",\n \"All publications and patent applications mentioned in the specification are indicative of the level of skill of those skilled in the art to which this invention pertains.\",\n \"All publications and patent applications are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.\",\n \"The use of the word “a” or “an” when used in conjunction with the term “comprising” in the claims and/or the specification may mean “one,” but it is also consistent with the meaning of “one or more,” “at least one,” and “one or more than one.” The use of the term “or” in the claims is used to mean “and/or” unless explicitly indicated to refer to alternatives only or the alternatives are mutually exclusive, although the disclosure supports a definition that refers to only alternatives and “and/or.” Throughout this application, the term “about” is used to indicate that a value includes the inherent variation of error for the device, the method being employed to determine the value, or the variation that exists among the study subjects.\",\n \"As used in this specification and claim(s), the words “comprising” (and any form of comprising, such as “comprise” and “comprises”), “having” (and any form of having, such as “have” and “has”), “including” (and any form of including, such as “includes” and “include”) or “containing” (and any form of containing, such as “contains” and “contain”) are inclusive or open-ended and do not exclude additional, unrecited elements or method steps Any part of this disclosure may be read in combination with any other part of the disclosure, unless otherwise apparent from the context.\",\n \"All of the compositions and/or methods disclosed and claimed herein can be made and executed without undue experimentation in light of the present disclosure.\",\n \"While the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those of skill in the art that variations may be applied to the compositions and/or methods and in the steps or in the sequence of steps of the method described herein without departing from the concept, spirit and scope of the invention.\",\n \"All such similar substitutes and modifications apparent to those skilled in the art are deemed to be within the spirit, scope and concept of the invention as defined by the appended claims.\",\n \"The present invention is described in more detail in the following non limiting Examples.\",\n \"Some embodiments of the technology described herein can be defined according to any of the following numbered paragraphs: 1.A method of treating or preventing a disease or condition in a human, wherein the disease or condition is mediated by a Target of Interest (TOI), wherein the TOI is present in humans as different polymorphic variants, the method comprising a. selecting a human that is positive for the TOI polymorphic variant, wherein the TOI in said human is encoded by a nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and/or wherein the TOI in said human is encoded by a nucleotide sequence comprising an allele having total human genotype frequency of less than 50%; and b. administering to the human an anti-TOI ligand to target the TOI in the human to treat or prevent said disease or condition.\",\n \"In an alternative where the TOI is human PCSK9, paragraph 1 provides:— A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation as defined herein (eg, I474V or E670G) in SEQ ID NO: 1, wherein the antibody comprises a VH domain derived from the recombination of a human VH segment, a human D gene segment and a human JH segment, the human VH segment encoding a valine at the amino acid corresponding to position 5 of SEQ ID NO: 40 and wherein said human comprises (i) a VH gene segment encoding the framework 1 of SEQ ID NO: 40 and (ii) a nucleotide sequence encoding a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation in SEQ ID NO: 1.In an alternative where the TOI is human PCSK9, paragraph 1 provides:— A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation as defined herein (eg, I474V or E670G) in SEQ ID NO: 1, wherein the antibody comprises a VL domain derived from the recombination of a human VL segment and a human JL segment, the human VL segment is a Vλ or Vκ disclosed herein and wherein said human comprises (i) said VL gene segment and (ii) a nucleotide sequence encoding a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation in SEQ ID NO: 1.In an alternative where the TOI is human PCSK9, paragraph 1 provides:— A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation as defined herein (eg, I474V or E670G) in SEQ ID NO: 1, wherein the antibody comprises a C domain encoded by a human CH, Cλ or Cκ gene segment disclosed herein and wherein said human comprises (i) said C gene segment and (ii) a nucleotide sequence encoding a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation in SEQ ID NO: 1.2.The method of paragraph 1, wherein before step (a) the ligand has been or is determined as being capable of specifically binding to said TOI variant.\",\n \"3.The method of paragraph 1 or 2, comprising determining that the human is positive for the TOI polymorphic variant, optionally wherein the step of determining comprises determining that the human is positive for a nucleotide variant encoding said TOI variant.\",\n \"4.The method of paragraph 3, wherein the step of determining comprises assaying a biological sample obtained from said human for a nucleotide polymorphism encoding said TOI polymorphic variant.\",\n \"5.The method of paragraph 3 or 4, wherein the step of determining comprises assaying a biological sample obtained from said human for a protein corresponding to the TOI polymorphic variant.\",\n \"6.The method of any preceding paragraph, wherein said frequency is less than 15%.\",\n \"7.The method of any preceding paragraph, wherein said frequency is less than 10%.\",\n \"8.The method of any preceding paragraph, wherein the ligand is capable of specifically binding to two or more different TOI variants, each being encoded by a nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.\",\n \"9.A method of treating or preventing a disease or condition in a human, wherein the disease or condition is mediated by a Target of Interest (TOI), wherein the TOI is present in humans as different polymorphic variants, the method comprising a. selecting a human that is negative for a variant nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%; or that the human is negative for a TOI variant encoded by a nucleotide sequence comprising the allele having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%; and b. administering to the human an anti-TOI ligand to target the TOI variant in the human and treat or prevent said disease or condition, wherein the TOI in said human is a variant encoded by a nucleotide sequence comprising an allele having a cumulative human allele frequency of more than 50% and/or having a total human genotype frequency of more than 50%.\",\n \"10.The method of paragraph 9, comprising determining that the human is positive for the TOI polymorphic variant, optionally wherein the determining comprises that the human has been or is phenotyped as positive for the most frequent TOI variant or genotyped for the nucleotide sequence thereof.\",\n \"11.The method of paragraph 10, wherein determining comprises assaying for the nucleotide sequence to determine the presence of said allele.\",\n \"12.The method of paragraph 11, wherein the assaying comprises nucleic acid amplification.\",\n \"13.The method of paragraph 11 or 12, wherein the assaying comprises hybridization, sequencing, or next generation sequencing.\",\n \"14.The method of any of paragraphs 11-13, further comprising the step of obtaining a biological sample from the human.\",\n \"15.The method of any one of paragraphs 9-14, wherein the ligand has been or is determined as being capable of specifically binding to the most frequent TOI variant.\",\n \"16.The method of any one of paragraphs 9-15, wherein the ligand has been or is determined as being substantially incapable of neutralising or inhibiting said TOI variant.\",\n \"17.The method of any one of paragraphs 9-16, wherein the ligand is capable of specifically binding to the most frequent TOI variant.\",\n \"18.The method of any one of paragraphs 9-17, wherein the ligand is capable of specifically binding to two or more different TOI variants, each being encoded by a nucleotide sequence comprising an allele having a cumulative human allele frequency of more than 50%.\",\n \"19.The method of any preceding paragraph, wherein said TOI polymorphic variant has been or is determined as being present in at least two different human ethnic populations.\",\n \"20.The method of any preceding paragraph, wherein said cumulative human allele frequency is the frequency in a database of naturally-occurring sequences sampled from at least 15 different human ethnic populations and comprising at least 1000 sequences.\",\n \"21.The method of any of the preceding paragraphs, wherein the ligand is an antibody, antibody fragment or an affibody.\",\n \"22.The method of any of the preceding paragraphs, wherein the ligand comprises a nucleotide sequence that specifically hybridises to a TOI nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50% or an RNA transcript thereof, and/or the ligand comprises a nucleotide sequence that comprises at least 10 contiguous nucleotides of a nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50% or is an antisense sequence thereof.\",\n \"23.The method of any of the preceding paragraphs, wherein the genome of said human comprises an allele having a cumulative human allele frequency of less than 50% and the allele is found in at least 2 different ethnic populations.\",\n \"24.A composition comprising a ligand capable of binding a target of interest encoded by a nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and the allele is found in at least 2 different ethnic populations and optionally a pharmaceutically acceptable carrier and optionally a label or instructions for use to treat and/or prevent said disease or condition in a human; optionally wherein the label or instructions comprise a marketing authorisation number issued by a regulatory authority.\",\n \"25.A kit for treating or preventing a condition or disease mediated by a target of interest as recited in any preceding paragraph, the kit comprising a ligand capable of specifically binding a target of interest encoded by a nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and the allele is found in at least 2 different ethnic populations; and optionally in combination with a label or instructions for use to treat and/or prevent said disease or condition in a human; optionally wherein the label or instructions comprise a marketing authorisation number issued by a regulatory agency; optionally wherein the kit comprises an injection pen or IV container that comprises the ligand.\",\n \"26.The composition of paragraph 24 or the kit of paragraph 25, wherein the regulatory agency is FDA or EMA.\",\n \"27.A method of producing an anti-human TOI antibody binding site, the method comprising obtaining a plurality of anti-TOI antibody binding sites, screening the antibody binding sites for binding to a TOI comprising an amino acid sequence encoded by a nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, or to a peptide thereof that comprises an amino acid variation from the corresponding sequence encoded by the TOI-encoding nucleotide sequence comprising an allele having the highest cumulative human allele frequency and/or the highest total human genotype frequency, and isolating an antibody binding site that binds in the screening step.\",\n \"28.A method of producing an anti-human TOI antibody, the method comprising immunising a non-human vertebrate with a TOI comprising an amino acid sequence encoded by a nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, or to a peptide thereof that comprises an amino acid variation from the corresponding sequence encoded by the TOI-encoding nucleotide sequence comprising an allele having the highest cumulative human allele frequency and/or the highest total human genotype frequency, and isolating an antibody that binds a TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, and optionally producing a TOI-binding fragment or derivative of the isolated antibody.\",\n \"29.The method of paragraph 28, wherein the non-human vertebrate is a mouse or a rat.\",\n \"30.The method of paragraph 29 or 30, comprising the step of obtaining a nucleic acid encoding the antibody, fragment, derivative or binding site and optionally inserting the nucleic acid in an expression vector.\",\n \"31.A kit for TOI genotyping a human, wherein the kit comprises a nucleic acid comprising a nucleotide sequence that specifically hybridises to a TOI nucleotide sequence selected having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50% or an RNA transcript thereof, and/or the nucleic acid comprises a nucleotide sequence that comprises at least 10 contiguous nucleotides of a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50% or is an antisense sequence thereof.\",\n \"32.A kit for TOI genotyping or phenotyping a human, wherein the kit comprises a ligand capable of binding a target of interest encoded by a nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% or an antibody, fragment or derivative produced by the method of any one of paragraphs 28 to 30.33.The kit of paragraph 32, wherein the allele is found in at least 2 different ethnic populations.\",\n \"34.Use of an anti-TOI ligand that specifically binds a human TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, in the manufacture of a medicament for treating and/or preventing a TOI-mediated disease or condition in a human whose genome comprises a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.\",\n \"35.Use of an anti-TOI ligand that specifically binds a human TOI comprising an amino acid sequence encoded by a TOI nucleotide sequence having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, in the manufacture of a medicament for targeting said TOI in a human to treat and/or prevent a disease or condition mediated by TOI.\",\n \"36.A method of targeting a Target of Interest (TOI) for treating and/or preventing a TOI-mediated disease or condition in a human, the method comprising administering an anti-TOI ligand to a human comprising a TOI nucleotide sequence comprising an allele selected as having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%, whereby a TOI encoded by said nucleotide sequence is targeted.\",\n \"37.The method of paragraph 36, wherein the method comprises targeting a human TOI comprising an amino acid sequence with said ligand to treat and/or prevent said disease or condition in said human, wherein said amino acid sequence is encoded by a nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50%.\",\n \"38.A method of Target of Interest (TOI) genotyping a nucleic acid sample of a human, the method comprising assaying in the sample the presence of a TOI nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.\",\n \"39.A method of Target of Interest (TOI) typing a protein sample of a human, the method comprising assaying the sample the presence of a TOI amino acid sequence encoded by a TOI nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50%.\",\n \"40.The method of paragraph 38 or 39, comprising obtaining a sample of serum, blood, faeces, hair, urine or saliva from a human, whereby the nucleic acid or protein sample is obtained for use in the step of assaying said sequence.\",\n \"41.The method of any one of paragraphs 38-40, comprising using a ligand capable of targeting a nucleic acid sequence comprising an allele having a cumulative human allele frequency of less than 50% and/or having a total human genotype frequency of less than 50% or a ligand capable of specifically binding the TOI encoded by said nucleic acid sequence to carry out said identifying step.\",\n \"42.A diagnostic kit comprising a ligand that is capable of binding a human Target of Interest (TOI) comprising an amino acid sequence encoded by a TOI nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50% and instructions for carrying out the method of any one of paragraphs 38-41.43.The diagnostic kit wherein the ligand is selected from an antibody, antibody fragment, antibody portion, affybody, oligonucleotide, modified oligonucleotide, antisense oligonucleotide, siRNA, and microRNA.\",\n \"44.A diagnostic kit comprising a nucleic acid probe comprising a nucleotide sequence that specifically hybridises a Target of Interest (TOI) nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and/or a total human genotype frequency of less than 50% or an RNA transcript thereof and instructions for carrying out the method of paragraph 38 or 39.45.The method, ligand, composition, kit or use of any preceding paragraph, wherein the TOI is encoded by a nucleotide sequence having a cumulative human allele frequency from 1 to 10% and/or a total human genotype frequency from 1 to about 15% or from 1 to 15%.\",\n \"46.The method, ligand, composition, kit or use of any preceding paragraph wherein the TOI is a human TOI selected from Table 5; optionally for treating and/or preventing a corresponding disease or condition as set out in Table 5.47.A method of treating or preventing a disease or condition in a human, wherein the disease or condition is mediated by a Target of Interest (TOI), wherein the TOI is present in humans as different polymorphic variants, the method comprising administering to the human determined to be positive for the TOI polymorphic variant, wherein the TOI in said human is encoded by a nucleotide sequence comprising an allele having a cumulative human allele frequency of less than 50% and/or wherein the TOI in said human is encoded by a nucleotide sequence comprising an allele having total human genotype frequency of less than 50% an anti-TOI ligand to target the TOI in the human to treat or prevent said disease or condition.\",\n \"48.The method of paragraph 47, wherein the anti-TOI ligand is selected from an antibody, an antibody portion, an antibody fragment, an affibody, an antisense oligonucleotide, an siRNA, and a microRNA.\",\n \"Additional Tailoring of Ligands to Genotype and/or Phenotype of the Human Patient As described herein, the present invention contemplates ligands (eg, antibodies and fragments) whose binding site specificities have been matched to one or more variant human TOIs (eg, PCSK9 or IL6R).\",\n \"Additionally or alternatively (and as further illustrated in the non-limiting Examples below), an optional aspect of the invention provides for matching of other features of the ligand to the patient's genotype or phenotype.\",\n \"In this respect, for example, the invention includes the ability to match amino acid sequence variation in a human patient to one or more ligand sequences or domains outside of the binding sites.\",\n \"For example, where the ligand comprises or consists of a human TOI-binding antibody or an anti-human TOI receptor Fc fusion, this aspect of the invention provides for more tailored matching of one or more constant region domains (eg, the Fc) to the patient genotype or phenotype.\",\n \"Additionally or alternatively, it is contemplated that sequence variation in the binding site can be similarly matched to the patient's genotype or phenotype.\",\n \"The present inventor has done this by considering the SNP occurrences in sequences encoding one or more parts of the ligand, eg, SNP occurrences in one, more or all of the gene segments from which the variable domain(s) and/or constant region domain(s) are derived.\",\n \"The inventor realised that it would be desirable to match the ligand to one or more corresponding variant SNPs found in the patient to be treated therapeutically and/or prophylactically.\",\n \"Matching could involve designing the ligand specifically for a patient of known phenotype and/or genotype, or matching could involve choosing a ligand by determining that there is correspondence between variation in the patient's phenotype or genotype with the variation in the ligand amino acid and/or corresponding nucleotides.\",\n \"A key consideration for the inventor was the desire to promote compatibility of the ligand with the patient's body, and in particular, the possible patient immune system responses to administered ligands.\",\n \"For example, it has been observed that human patients receiving human or humanised antibody drugs may mount an immune response against the incoming antibody (a so-called HAHA response) which results in the patient producing anti-drug antibodies as a result of the patient's immune system recognising the drug as foreign.\",\n \"For example, studies have suggested that some patients receiving HUMIRA™ (adalimumab), currently the biggest selling antibody medicine, mount a HAHA immune response against the medicine, and this may impact treatment adversely.\",\n \"Reference is made to JAMA.\",\n \"2011; 305(14): 1460-1468.doi: 10.1001/jama.2011.406: “Development of Antidrug Antibodies Against Adalimumab and Association With Disease Activity and Treatment Failure During Long-term Follow-up”, G M Bartelds et al.\",\n \"The authors concluded that results of this study showed that development of antidrug antibodies was associated with a negative outcome of adalimumab treatment in human RA patients.\",\n \"It was reported that not only did patients with anti-adalimumab antibodies discontinue treatment more often and earlier than patients without anti-adalimumab antibodies, they also had a higher disease activity during treatment and only rarely came into remission.\",\n \"In addition, reportedly the data showed that two-thirds of the anti-adalimumab antibody-positive patients developed these antibodies in the first 28 weeks of treatment and that the presence of anti-adalimumab antibodies substantially influenced serum adalimumab concentrations.\",\n \"This HAHA theme is, therefore, a significant concern and this has been considered by the regulatory authorities.\",\n \"For example, the European Medicines Agency (EMA) has issued a “Guideline on immunogenicity assessment of monoclonal antibodies intended for in vivo clinical use” (available on the world wide web at ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/06/WC500128688.pdf, EMA/CHMP/BMWP/86289/2010, addendum to EMEA/CHMP/BMWP/14327/2006), which came into force on 1 Dec. 2012.As such, it is good practice for researchers to identify and assess risk of anti-antibody drug occurrence and effects.\",\n \"The present aspect of the invention, by more closely tailoring the ligand itself (as well as its specificity) to the patient, helps to address these considerations when designing and administering anti-human TOI medicines for treating and/or preventing human TOI-related diseases and conditions.\",\n \"The inventor also considered the desirability to tailor the variation in the ligand constant region (eg, for an antibody or Fc-containing ligand), mindful that then the constant region being administered to the patient would be tuned to the various components, such as patient's Fc receptors, that would interact with the constant region in the patient.\",\n \"Good Fc/Fc receptor interactions can be important for drug recycling (via the FcRn) to provide for useful half-lives in vivo or for use in cell killing, eg, for cancer indications.\",\n \"In this way it is possible, therefore, to tune the effector function of the constant region (eg, Fc) to the patient more closely, to promote efficacy.\",\n \"For example, more efficacious drugs are desirable for better patient treatment and may provide the possibility of lowered dosing and/or dosing frequencies.\",\n \"Thus, in examples of this aspect, the invention provides the following (set out as clauses):— 1.The ligand, method, use, kit or composition of the invention, wherein (i) the ligand (eg, antibody or fragment) comprises (c) a variable domain that is encoded by a human V region nucleotide sequence, wherein the V nucleotide sequence is derived from recombination of human VH, D and JH gene segments or human VL and JL gene segments; or (d) a constant region domain encoded by a C region gene segment; Wherein a first gene segment of said gene segments of (a), or said C region gene segment of (b) comprises a first single nucleotide polymorphism (SNP) encoding a first amino acid polymorphism; and (ii) the genome of said human comprises said first SNP or wherein said human expresses (a′) an antibody variable domain comprising said first amino acid polymorphism or (b′) an antibody constant domain comprising said first amino acid polymorphism.\",\n \"2.The ligand, method, use, kit or composition of clause 1, wherein blood of said human comprises substantially no antibodies that specifically bind to the domain comprising said first amino acid polymorphism as determined in an in vitro binding assay.\",\n \"3.The ligand, method, use, kit or composition of clause 2, wherein SPR is used to carry out said assay.\",\n \"In an alternative, ELISA is used.\",\n \"4.The ligand, method, use, kit or composition of any one of clauses 1 to 3, wherein the genome of said human comprises said first gene segment (when (a) applies) or said C region gene segment (when (b) applies).\",\n \"5.The ligand, method, use, kit or composition of any one of clauses 1 to 4, wherein said first segment or a second segment of said segments of (a), or said C region gene segment of (b), comprises a second SNP encoding a second amino acid polymorphism; and wherein the genome of said human comprises said second SNP or wherein said human expresses (a″) an antibody variable domain comprising said second amino acid polymorphism or (b″) an antibody constant region domain comprising said first and second amino acid polymorphisms.\",\n \"6.The ligand, method, use, kit or composition of clause 5, wherein said human expresses an antibody variable domain comprising said first and second amino acid polymorphisms.\",\n \"7.The ligand, method, use, kit or composition of clause 5 or 6, wherein the first and second SNPs of said genome are comprised by the same antibody gene segment.\",\n \"For example, the first and second SNPs of the genome are comprised by an IGHG1*01 gene segment and said first segment of (a) is an IGHG1*01 gene segment.\",\n \"For example, the first and second SNPs of the genome are comprised by an IGHG2*01 gene segment and said first segment of (a) is an IGHG2*01 gene segment.\",\n \"8.The ligand, method, use, kit or composition of any one of clauses 1 to 7, wherein each SNP is a variable region gene segment SNP.\",\n \"9.The ligand, method, use, kit or composition of any one of clauses 1 to 7, wherein each SNP is a constant region gene segment SNP, eg each SNP is a gamma-1 constant region gene segment SNP, or a gamma-2 constant region gene segment SNP, or a gamma-3 constant region gene segment SNP or a gamma-4 constant region gene segment SNP.\",\n \"10.The ligand, method, use, kit or composition of clause 9, wherein the first SNP is a CH1, CH2, CH3 or CH4 gene segment SNP and/or the second SNP is a CH1, CH2, CH3 or CH4 gene segment SNP.\",\n \"11.The ligand, method, use, kit or composition of any one of clauses 1 to 8, wherein each SNP is a variable domain SNP, eg, a VH domain SNP, or a Vκ domain SNP, or a Vλ SNP.\",\n \"12.The ligand, method, use, kit or composition of any one of clauses 1 to 11, wherein said constant region domain of (b) is comprised by an antibody Fc region.\",\n \"13.The ligand, method, use, kit or composition of any one of clauses 1 to 12, wherein the ligand (eg, antibody or fragment) has been determined to specifically bind one or more human TOI variants as disclosed herein, for example, with a KD of 1 nM or less (eg, 100 or 10 pM or less) as determined by SPR.\",\n \"14.The ligand, method, use, kit or composition of the invention (eg, according to any one of clauses 1 to 13), wherein the ligand comprises or consists of an antibody or fragment that comprises a human antibody variable domain derived from the recombination of a human V gene segment and a human J gene segment (and optionally a human D gene segment when the variable domains are VH domains); and wherein the genome of the human comprises said human V gene segment and/or the human expresses antibodies comprising antibody variable domains derived from the recombination of said human V gene segment and a human J gene segment (and optionally a human D gene segment).\",\n \"In an example, the V gene segment is any of the V gene segments disclosed in WO2013041844, a 1000 Genomes database and/or www.imgt.org, the disclosures of which (including disclosure relating to sequence) is explicitly incorporated herein by reference for use in the present invention.\",\n \"15.The ligand, method, use, kit or composition of the invention (eg, according to any one of clauses 1 to 14), wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused human TOI receptor) comprises a human heavy chain constant domain encoded by a first constant region nucleotide sequence; and wherein the genome of the human comprises a heavy chain constant region nucleotide sequence that is identical to said first constant region nucleotide sequence and/or the human expresses antibodies comprising said human constant domain.\",\n \"16.The ligand, method, use, kit or composition of the invention (eg, according to any one of clauses 1 to 15), wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused human TOI receptor) comprises a human gamma heavy chain CH1 domain encoded by a CH1 nucleotide sequence; and wherein the genome of the human comprises a gamma heavy chain constant region nucleotide sequence that is identical to said CH1 nucleotide sequence and/or the human expresses antibodies comprising said human gamma CH1 domain.\",\n \"17.The ligand, method, use, kit or composition of the invention (eg, according to any one of clauses 1 to 16), wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused human TOI receptor) comprises a human gamma heavy chain CH2 domain encoded by a CH2 nucleotide sequence; and wherein the genome of the human comprises a gamma heavy chain constant region nucleotide sequence that is identical to said CH2 nucleotide sequence and/or the human expresses antibodies comprising said human gamma CH2 domain.\",\n \"18.The ligand, method, use, kit or composition of the invention (eg, according to any one of clauses 1 to 17), wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused human TOI receptor) comprises a human gamma heavy chain CH3 domain encoded by a CH3 nucleotide sequence; and wherein the genome of the human comprises a gamma heavy chain constant region nucleotide sequence that is identical to said CH3 nucleotide sequence and/or the human expresses antibodies comprising said human gamma CH3 domain.\",\n \"19.The ligand, method, use, kit or composition of the invention (eg, according to any one of clauses 1 to 18), wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused human TOI receptor) comprises a human gamma heavy chain CH4 domain encoded by a CH4 nucleotide sequence; and wherein the genome of the human comprises a gamma heavy chain constant region nucleotide sequence that is identical to said CH4 nucleotide sequence and/or the human expresses antibodies comprising said human gamma CH4 domain.\",\n \"20.The ligand, method, use, kit or composition of the invention (eg, according to any one of clauses 1 to 19), wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused human TOI receptor) comprises a human gamma heavy chain Fc region encoded by a Fc nucleotide sequence; and wherein the genome of the human comprises a gamma heavy chain constant region nucleotide sequence that is identical to said Fc nucleotide sequence and/or the human expresses antibodies comprising said human gamma Fc region.\",\n \"21.The ligand, method, use, kit or composition of any one of clauses 16 to 20, wherein said human gamma heavy chain is a human gamma-1 heavy chain.\",\n \"22.The ligand, method, use, kit or composition of any one of clauses 16 to 20, wherein said human gamma heavy chain is a human gamma-2 heavy chain.\",\n \"23.The ligand, method, use, kit or composition of any one of clauses 16 to 20, wherein ligand comprises a human IGHG1*01 gamma-1 heavy chain constant region.\",\n \"24.The ligand, method, use, kit or composition of any one of clauses 16 to 20, wherein ligand comprises a human IGHG2*01 gamma-1 heavy chain constant region.\",\n \"25.The ligand, method, use, kit or composition of any one of clauses 15 to 24, wherein the human has been or is genotyped as positive for said heavy chain constant region nucleotide sequence.\",\n \"26.The ligand, method, use, kit or composition of clause 23, wherein the human has been or is genotyped as positive for human IGHG1*01 nucleotide sequence.\",\n \"27.The ligand, method, use, kit or composition of clause 24, wherein the human has been or is genotyped as positive for human IGHG2*01 nucleotide sequence.\",\n \"28.The ligand, method, use, kit or composition of any one of clauses 16 to 24, wherein the human has been or is phenotyped as positive for said gamma heavy chain constant domain, CH1, CH2, CH3, CH4 or Fc.\",\n \"29.The ligand, method, use, kit or composition of clause 28, (i) when dependent from clause 23, wherein the human has been or is phenotyped as positive for a human IGHG1*01 gamma heavy chain constant domain, CH1, CH2, CH3, CH4 or Fc or (ii) when dependent from clause 24, wherein the human has been phenotyped as positive for a human IGHG2*01 gamma heavy chain constant domain, CH1, CH2, CH3, CH4 or Fc.\",\n \"30.The method or use of any one of clauses 16 to 24 and 26 to 29, comprising genotyping the human as positive for said gamma heavy chain constant region nucleotide sequence, eg, positive for said gamma heavy chain constant domain, CH1, CH2, CH3, CH4 or Fc nucleotide sequence; positive for said human IGHG1*01 gamma heavy chain constant region, CH1, CH2, CH3, CH4 or Fc nucleotide sequence; or positive for said human IGHG2*01 gamma heavy chain constant region, CH1, CH2, CH3, CH4 or Fc nucleotide sequence.\",\n \"31.The method or use of any one of clauses 16 to 24 and 26 to 30, comprising phenotyping the human as positive for said gamma heavy chain constant region, eg, positive for said gamma heavy chain constant domain, CH1, CH2, CH3, CH4 or Fc; positive for said human IGHG1*01 gamma heavy chain constant domain, CH1, CH2, CH3, CH4 or Fc; or positive for said human IGHG2*01 gamma heavy chain constant domain, CH1, CH2, CH3, CH4 or Fc.\",\n \"Examples of Tailored Ligands The inventor analysed amino acid variability and distribution amongst large representative human samples.\",\n \"The result of the analysis for example antibody gene segments is shown in Table 9.In a first example, the inventor identified the possibility of addressing the rarer IGH-gamma-1 SNPs 204D (observed cumulative frequency of 0.296) and 206L (observed cumulative frequency of 0.283) individually or in combination.\",\n \"These residues are part of the CH3 domain, and as such they form part of antibody Fc regions.\",\n \"Thus, matching of these CH3 variations with the patient is especially beneficial for reasons as discussed above.\",\n \"Thus, this example provides aspects set out in the following clauses.\",\n \"32.The ligand, method, use, kit or composition of the invention (eg, according to any one of clauses 1 to 31), wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused TOI receptor) comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 or a Leu corresponding to position 206 of SEQ ID NO: 42 and wherein the genome of the human comprises a gamma-1 heavy chain constant region nucleotide sequence that encodes such an Asp or Leu or the human expresses antibodies comprising human gamma-1 constant regions comprising such an Asp or Leu.\",\n \"The skilled person will be familiar with techniques for determining genome sequences of a human, eg, by using a sample containing genomic DNA and/or RNA, sequencing and comparing using bioinformatics or other computer tools to compare the sampled sequence with sequences of human alleles (eg, as shown in the IMGT, 100 genomes or other database as disclosed herein).\",\n \"In an example, the sample is a blood or saliva or cheek swab sample.\",\n \"33.The ligand, method, use, kit or composition of clause 32, wherein the ligand comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 and a Leu corresponding to position 206 of SEQ ID NO: 42.34.The ligand, method, use, kit or composition of clause 32 or 33, wherein the genome of the human comprises a gamma-1 heavy chain constant region nucleotide sequence that encodes such an Asp and Leu or the human expresses antibodies comprising human gamma-1 constant regions comprising such an Asp and Leu.\",\n \"35.The ligand, method, use, kit or composition of clause 32, 33 or 34, wherein the ligand comprises a human IGHG1*01 gamma-1 heavy chain constant region, eg, an Fc, CH1, CH2 and/or CH3 domain encoded by human IGHG1*01.36.The ligand, method, use, kit or composition of any one of clauses 32 to 35, wherein the genome of the human comprises a human IGHG1*01 nucleotide sequence or the human expresses antibodies comprising human constant domains encoded by a human IGHG1*01 nucleotide sequence.\",\n \"37.The ligand, method, use, kit or composition of any one of clauses 32 to 36, wherein the ligand comprises a hinge region encoded by human IGHG1*01.38.The ligand, method, use, kit or composition of any one of clauses 32 to 37, wherein the ligand comprises or consists of an antibody, wherein the antibody comprises heavy chains that comprise SEQ ID NO: 61.39.The ligand, method, use, kit or composition of any one of clauses 32 to 38, wherein the human is of European ancestry.\",\n \"As shown in Table 9, 204D and 206L are found in such humans.\",\n \"40.The ligand, method, use, kit or composition of any one of clauses 32 to 39, wherein the human has been or is genotyped as positive for said Asp and/or Leu.\",\n \"41.The ligand, method, use, kit or composition of any one of clauses 32 to 40, wherein the human has been or is genotyped as positive for human IGHG1*01.42.The ligand, method, use, kit or composition of any one of clauses 32 to 41, wherein the human has been or is phenotyped as positive for a human IGHG1*01 CH3.43.The method or use of any one of clauses 32 to 42, comprising selecting a said human whose genome comprises a codon(s) encoding said Asp and/or Leu; comprises human IGHG1*01; or comprises a human IGHG1*01 CH3.44.The method or use of any one of clauses 32 to 43, comprising selecting a said human whose phenotype comprises said Asp and/or Leu; a human IGHG1*01 region; or a human IGHG1*01 CH3.44a.\",\n \"The ligand, method, use, kit or composition of any one of clauses 32 to 44, wherein the human expresses antibodies comprising human gamma-1 constant regions comprising such an Asp and Leu.\",\n \"In a second example, the inventor identified the possibility of addressing IGH-gamma-2 SNPs.\",\n \"This included consideration of Fc region variation—in this respect, the inventor focused on positions 161 and 257 which are in the Fc region.\",\n \"Thus, this example provides aspects set out in the following clauses.\",\n \"45.The ligand, method, use, kit or composition of the invention (eg, according to any one of clauses 1 to 31), wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused TOI receptor) comprises a human gamma-2 heavy chain constant region that comprises an amino acid selected from the group consisting of a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44, a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44; and wherein the genome of the human comprises a gamma-2 heavy chain constant region nucleotide sequence that encodes such a selected amino acid or the human expresses antibodies comprising human gamma-2 constant regions comprising such a selected amino acid.\",\n \"46.The ligand, method, use, kit or composition of clause 45, wherein the ligand comprises a human gamma-2 heavy chain constant region that comprises (i) a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44 and optionally (ii) a Val corresponding to position 161 of SEQ ID NO: 44 and/or an Ala corresponding to position 257 of SEQ ID NO: 44; and wherein the genome of the human comprises a gamma-2 heavy chain constant region nucleotide sequence that encodes such amino acids of (i) or the human expresses antibodies comprising human gamma-2 constant regions comprising such amino acids of (i).\",\n \"This example focuses on CH1 variation.\",\n \"47.The ligand, method, use, kit or composition of clause 45 or 46, wherein the ligand comprises a human gamma-2 heavy chain constant region that comprises (i) a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44 and optionally (ii) an amino acid selected from the group consisting of a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44 and a Phe corresponding to position 76 of SEQ ID NO: 44; and wherein the genome of the human comprises a gamma-2 heavy chain constant region nucleotide sequence that encodes such amino acids of (i) or the human expresses antibodies comprising human gamma-2 constant regions comprising such amino acids of (i).\",\n \"This example focuses on Fc variation.\",\n \"48.The ligand, method, use, kit or composition of any one of clauses 45 to 47, wherein the ligand comprises a human IGHG2*01 gamma-2 heavy chain constant region, eg, an Fc, CH1, CH2 and/or CH3 domain encoded by human IGHG2*01.49.The ligand, method, use, kit or composition of any one of clauses 45 to 48, wherein the genome of the human comprises a human IGHG2*01 nucleotide sequence or the human expresses antibodies comprising human constant domains encoded by a human IGHG2*01 nucleotide sequence.\",\n \"50.The ligand, method, use, kit or composition of any one of clauses 45 to 49, wherein the ligand comprises a hinge region encoded by human IGHG2*01.51.The ligand, method, use, kit or composition of any one of clauses 45 to 50, wherein the ligand comprises or consists of an antibody, wherein the antibody comprises heavy chains that comprise SEQ ID NO: 63 or 65.52.The ligand, method, use, kit or composition of any one of clauses 45 to 51, wherein the human is of European, African American, or European American ancestry.\",\n \"53.The ligand, method, use, kit or composition of any one of clauses 45 to 52, wherein the human has been or is genotyped as positive for one, more or all of said Pro, Asn, Phe, Val and Ala. 54.The ligand, method, use, kit or composition of any one of clauses 45 to 53, wherein the human has been or is genotyped as positive for human IGHG2*01.55.The ligand, method, use, kit or composition of any one of clauses 45 to 54, wherein the human has been or is phenotyped as positive for a human IGHG2*01 CH1.56.The ligand, method, use, kit or composition of any one of clauses 45 to 55, wherein the human has been or is phenotyped as positive for a human IGHG2*01 CH2.57.The ligand, method, use, kit or composition of any one of clauses 45 to 56, wherein the human has been or is phenotyped as positive for a human IGHG2*01 CH3.58.The method or use of any one of clauses 45 to 57, comprising selecting a said human whose genome comprises a codon(s) encoding one, more or all of said Pro, Asn, Phe, Val and Ala; comprises human IGHG2*01; or comprises a human IGHG2*01 CH1, CH2 and/or CH3.59.The method or use of any one of clauses 45 to 58, comprising selecting a said human whose phenotype comprises one, more or all of said Pro, Asn, Phe, Val and Ala; a human IGHG2*01 region; or a human IGHG2*01 CH1, CH2 and/or CH3.60.The ligand, method, use, kit or composition of any one of clauses 45 to 59, wherein the human expresses antibodies comprising human gamma-2 constant regions comprising such a Pro, Asn, Phe, Val and Ala.\",\n \"In a third example, the inventor addressed human kappa constant region variation.\",\n \"Thus, the present aspect of the invention also provides the following.\",\n \"61.The ligand, method, use, kit or composition of the invention (eg, according to any one of clauses 1 to 60), wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused TOI receptor) comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 or a Cys corresponding to position 87 of SEQ ID NO: 50; and wherein the genome of the human comprises a kappa light chain constant region nucleotide sequence that encodes such a Val or Cys or the human expresses antibodies comprising human kappa light chain constant regions comprising such a Val or Cys.\",\n \"62.The ligand, method, use, kit or composition of clause 61, wherein the ligand comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 and a Cys corresponding to position 87 of SEQ ID NO: 50.63.The ligand, method, use, kit or composition of clause 61 or 62, wherein the genome of the human comprises a kappa light chain constant region nucleotide sequence that encodes such a Val and Cys or the human expresses antibodies comprising human kappa constant regions comprising such a Val and Cys.\",\n \"64.The ligand, method, use, kit or composition of any one of clauses 61 to 63, wherein the antibody or fragment comprises a human IGKC*01 kappa light chain constant region.\",\n \"65.The ligand, method, use, kit or composition of any one of clauses 61 to 64, wherein the ligand comprises or consists of an antibody, wherein the antibody comprises light chains that comprise SEQ ID NO: 62 or 66.66.The ligand, method, use, kit or composition of any one of clauses 61 to 65, wherein the ligand comprises or consists of an antibody, wherein the antibody comprises a light chain variable domain derived from recombination of a human Vκ gene segment and a human Jκ gene segment, wherein the Jκ gene segment is IGKJ2*01 (SEQ ID NO: 57).\",\n \"67.The ligand, method, use, kit or composition of any one of clauses 61 to 66, wherein the human has been or is phenotyped as positive for said Val and/or Cys.\",\n \"68.The ligand, method, use, kit or composition of any one of clauses 61 to 67, wherein the human has been or is genotyped as positive for human IGKC*01.69.The ligand, method, use, kit or composition of any one of clauses 61 to 68, wherein the human has been or is phenotyped as positive for a human IGKC*01 domain.\",\n \"70.The method or use of any one of clauses 61 to 69, comprising selecting a said human whose genome comprises a codon(s) encoding said Val and/or Cys; or comprises human IGKC*01.71.The method or use of any one of clauses 61 to 70, comprising selecting a said human whose phenotype comprises such a Val and/or Cys; or comprises a human IGKC*01 domain.\",\n \"72.The ligand, method, use, kit or composition of any one of clauses 61 to 71, wherein the human expresses antibodies comprising human kappa constant domains comprising such a Val and Cys, eg, expresses human IGKC*01 constant domains.\",\n \"In a fourth example, the inventor addressed human lambda constant region variation.\",\n \"Thus, this example provides aspects set out in the following clauses.\",\n \"73.The ligand, method, use, kit or composition of the invention (eg, according to any one of clauses 1 to 60), wherein the ligand (eg, comprising or consisting of an antibody or fragment or an Fc-fused TOI receptor) comprises a human IGLC2*01 light chain constant region; and wherein the genome of the human comprises a human IGLC2*01 nucleotide sequence or the human expresses antibodies comprising human light chain IGLC2*01 constant regions.\",\n \"74.The ligand, method, use, kit or composition of clause 73, wherein the antibody comprises light chains that comprise SEQ ID NO: 64.75.The ligand, method, use, kit or composition of clause 73 or 74, wherein the human has been or is genotyped as positive for human IGLC2*01.76.The ligand, method, use, kit or composition of any one of clauses 73 to 75, wherein the human has been or is phenotyped as positive for a human IGLC2*01 domain.\",\n \"77.The method or use of any one of clauses 73 to 76, comprising selecting a said human whose genome comprises human IGLC2*01.78.The method or use of any one of clauses 73 to 77, comprising selecting a said human whose phenotype comprises a human IGLC2*01 domain.\",\n \"79.The ligand, method, use, kit or composition of any one of clauses 73 to 78, wherein the human expresses antibodies comprising human lambda IGLC2*01 constant domains.\",\n \"In a fifth example, the inventor addressed human heavy chain variable region variation.\",\n \"Thus, this example provides aspects set out in the following clauses.\",\n \"80.The ligand, method, use, kit or composition of the invention (eg, according to any one of clauses 1 to 79), wherein the ligand comprises or consists of an antibody or fragment, wherein the antibody or fragment comprises a VH domain that is derived from the recombination of a human VH gene segment, a human D gene segment and a human JH gene segment, wherein the VH gene segment is selected from the group consisting of (i) IGHV1-18*01 and the genome of the human comprises a human IGHV1-18*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGHV1-18*01; or (ii) IGVH1-46*01 and the genome of the human comprises a human IGHV1-46*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGHV1-46*01.81.The ligand, method, use, kit or composition of clause 80, wherein the antibody or fragment comprises a one more or all of a CH1 domain, CH2 domain, CH3 domain, hinge or Fc encoded by human IGHG2*01.82.The ligand, method, use, kit or composition of clause 80 or 81, wherein the antibody or fragment comprises heavy chains that comprise SEQ ID NO: 63 or 65.83.The ligand, method, use, kit or composition of any one of clauses 80 to 82, wherein the human has been or is genotyped as positive for said selected VH gene segment, positive for human IGHV1-18*01 or IGVH1-46*01.84.The method or use of any of clauses 80 to 83, comprising genotyping the human as positive for said selected VH gene segment, eg, positive for human IGHV1-18*01 or IGVH1-46*01.In a sixth example, the inventor addressed human light chain variable region variation.\",\n \"Thus, this example provides aspects set out in the following clauses.\",\n \"85.The ligand, method, use, kit or composition of the invention (eg, according to any one of clauses 1 to 84), wherein the ligand comprises or consists of an antibody or fragment, wherein the antibody or fragment comprises a VL domain that is derived from the recombination of a human VL gene segment and a human JL gene segment, wherein the VL gene segment is selected from the group consisting of (i) IGKV4-1*01 and the genome of the human comprises a human IGKV4-1*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGKV4-1*01; (ii) IGLV2-14*01 and the genome of the human comprises a human IGLV2-14*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGLV2-14*01; or (iii) IGKV1-13*02 and the genome of the human comprises a human IGKV1-13*02 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGKV1-13*02.86.The ligand, method, use, kit or composition of clause 85, wherein the antibody comprises light chains that comprise SEQ ID NO: 62, 64 or 66.87.The ligand, method, use, kit or composition of clause 85 or 86, wherein the antibody or fragment comprises a light chain variable domain derived from recombination of a human Vκ gene segment and a human Jκ gene segment, wherein the Jκ gene segment is IGKJ2*01 (SEQ ID NO: 57; wherein (i) or (iii) applies.\",\n \"88.The ligand, method, use, kit or composition of any one of clauses 85 to 87, wherein the human has been or is genotyped as positive for said selected VL gene segment, eg, positive for human IGKV4-1*01, IGLV2-14*01 or IGKV1-13*02.89.The method or use of clause 88, comprising genotyping the human as positive for said selected VL gene segment, eg, genotyping the human as positive for human IGKV4-1*01, IGLV2-14*01 or IGKV1-13*02.90.The ligand, method, use, kit or composition of any one of clauses 1 to 89, wherein the ligand (eg, antibody or fragment) binds said human TOI with a dissociation constant (Kd) of 1 nM or less as determined by SPR, (eg, 100, 10 or 1 pM or less).\",\n \"EXAMPLES Example 1: Rare PCSK9 Variants Proprotein convertase subtilisin kexin type 9 (PCSK9) is a serine protease involved in regulating the levels of the low density lipoprotein receptor (LDLR) protein (Horton et al., 2007; Seidah and Prat, 2007).\",\n \"In vitro experiments have shown that adding PCSK9 to HepG2 cells lowers the levels of cell surface LDLR (Benjannet et al., 2004; Lagace et al., 2006; Maxwell et al., 2005; Park et al., 2004).\",\n \"Experiments with mice have shown that increasing PCSK9 protein levels decreases levels of LDLR protein in the liver (Benjannet et al., 2004; Lagace et al., 2006; Maxwell et al., 2005; Park et al., 2004), while PCSK9 knockout mice have increased levels of LDLR in the liver (Rashid et al., 2005).\",\n \"Additionally, various human PCSK9 mutations that result in either increased or decreased levels of plasma LDL have been identified (Kotowski et al., 2006; Zhao et al., 2006).\",\n \"PCSK9 has been shown to directly interact with the LDLR protein, be endocytosed along with the LDLR, and co-immunofluoresce with the LDLR throughout the endosomal pathway (Lagace et al., 2006).\",\n \"PCSK9 is a prohormone-proprotein convertase in the subtilisin (S8) family of serine proteases (Seidah et al., 2003).\",\n \"Humans have nine prohormone-proprotein convertases that can be divided between the S8A and S8B subfamilies (Rawlings et al., 2006).\",\n \"Furin, PC1/PC3, PC2, PACE4, PC4, PC5/PC6 and PC7/PC8/LPC/SPC7 are classified in subfamily S8B.\",\n \"Crystal and NMR structures of different domains from mouse furin and PC1 reveal subtilisin-like pro- and catalytic domains, and a P domain directly C-terminal to the catalytic domain (Henrich et al., 2003; Tangrea et al., 2002).\",\n \"Based on the amino acid sequence similarity within this subfamily, all seven members are predicted to have similar structures (Henrich et al., 2005).\",\n \"SKI-1/SIP and PCSK9 are classified in subfamily S8A.\",\n \"Sequence comparisons with these proteins also suggest the presence of subtilisin-like pro- and catalytic domains (Sakai et al., 1998; Seidah et al., 2003; Seidah et al., 1999).\",\n \"In these proteins the amino acid sequence C-terminal to the catalytic domain is more variable and does not suggest the presence of a P domain.\",\n \"Prohormone-proprotein convertases are expressed as zymogens and they mature through a multi step process.\",\n \"The function of the pro-domain in this process is two-fold.\",\n \"The pro-domain first acts as a chaperone and is required for proper folding of the catalytic domain (Ikemura et al., 1987).\",\n \"Once the catalytic domain is folded, autocatalysis occurs between the pro-domain and catalytic domain.\",\n \"Following this initial cleavage reaction, the pro-domain remains bound to the catalytic domain where it then acts as an inhibitor of catalytic activity (Fu et al., 2000).\",\n \"When conditions are correct, maturation proceeds with a second autocatalytic event at a site within the pro-domain (Anderson et al., 1997).\",\n \"After this second cleavage event occurs the pro-domain and catalytic domain dissociate, giving rise to an active protease.\",\n \"Autocatalysis of the PCSK9 zymogen occurs between Gln152 and Ser153 (VFAQ|SIP (SEQ ID NO: 67)) (Naureckiene et al., 2003), and has been shown to be required for its secretion from cells (Seidah et al., 2003).\",\n \"A second autocatalytic event at a site within PCSK9's pro-domain has not been observed.\",\n \"Purified PCSK9 is made up of two species that can be separated by non-reducing SDS-PAGE; the pro-domain at 17 Kd, and the catalytic plus C-terminal domains at 65 Kd.\",\n \"PCSK9 has not been isolated without its inhibitory pro-domain, and measurements of PCSK9's catalytic activity have been variable (Naureckiene et al., 2003; Seidah et al., 2003).\",\n \"In certain embodiments, a PCSK9 polypeptide includes terminal residues, such as, but not limited to, leader sequence residues, targeting residues, amino terminal methionine residues, lysine residues, tag residues and/or fusion protein residues.\",\n \"“PCSK9” has also been referred to as FH3, NARC1, HCHOLA3, proprotein convertase subtilisin/kexin type 9, and neural apoptosis regulated convertase 1.The PCSK9 gene encodes a proprotein convertase protein that belongs to the proteinase K subfamily of the secretory subtilase family.\",\n \"The term “PCSK9” denotes both the proprotein and the product generated following autocatalysis of the proprotein.\",\n \"When only the autocatalyzed product is being referred to (such as for an antigen binding protein or ligand that binds to the cleaved PCSK9), the protein can be referred to as the “mature,” “cleaved”, “processed” or “active” PCSK9.When only the inactive form is being referred to, the protein can be referred to as the “inactive”, “pro-form”, or “unprocessed” form of PCSK9.The term PCSK9 also encompasses PCSK9 molecules incorporating post-translational modifications of the PCSK9 amino acid sequence, such as PCSK9 sequences that have been glycosylated, PCSK9 sequences from which its signal sequence has been cleaved, PCSK9 sequence from which its pro domain has been cleaved from the catalytic domain but not separated from the catalytic domain (see, e.g., FIGS.\",\n \"1A and 1B of US20120093818A1; which is incorporated by reference herein in its entirety).\",\n \"The present invention provides anti-PCSK9 ligands; and PCSK9-binding or targeting ligands as described herein.\",\n \"The ligands have a variety of utilities.\",\n \"Some of the ligands, for instance, are useful in specific binding assays, for genotyping or phenotyping humans, affinity purification of PCSK9, in particular human PCSK9 or its ligands and in screening assays to identify other antagonists of PCSK9 activity.\",\n \"Some of the ligands of the invention are useful for inhibiting binding of PCSK9 to LDLR, or inhibiting PCSK9-mediated activities.\",\n \"Anti-PCSK9 ligands (eg, antibodies and anti-sense RNA) have been developed based on targeting and neutralising so-called “wild-type” human PCSK9, which is a commonly-occurring form (see, eg, US20120093818A1 and US20110065902A1; each of which is incorporated by reference herein in its entirety).\",\n \"While such therapies are useful for human patients harbouring this form of human PCSK9, the inventor considered it useful to investigate the possibility of targeting much rarer—but still naturally-occurring—forms of PCSK9 amongst human populations.\",\n \"In this way, the inventor arrived at insight into the natural occurrences and distributions of rarer human PCSK9 forms that can serve as useful targets (at the protein or nucleic acid level) for human treatment, prophylaxis and diagnosis pertinent to diseases and conditions mediated or associated with PCSK9 activity.\",\n \"This particularly provides for tailored therapies, prophylaxis and diagnosis in humans that are devoid of the common PCSK9 gene or protein (ie, the form a or a′ as used in US20120093818A1 and US20110065902A1 to generate antibodies).\",\n \"The skilled person will know that SNPs or other changes that translate into amino acid variation can cause variability in activity and/or conformation of human targets to be addressed.\",\n \"This has spawned great interest in personalized medicine where genotyping and knowledge of protein and nucleotide variability is used to more effectively tailor medicines and diagnosis of patients.\",\n \"The invention, therefore, provides for tailored pharmaceuticals and testing that specifically addresses rarer PCSK9 polymorphic variant forms.\",\n \"Such forms or “alleles” (at the nucleotide level), in many of the examples determined by the inventor, comprise multiple changes at the nucleotide and amino acid levels from the corresponding common form nucleotide and amino acids sequences, ie, there are multiple non-synonymous changes at the nucleotide level that translate into multiple corresponding changes in the protein target in humans.\",\n \"Furthermore, the inventor surprisingly realised that the rarer natural forms, although present in humans at much lower frequencies than the common form, nevertheless are represented in multiple and ethnically-diverse human populations and usually with many human examples per represented ethnic population.\",\n \"Thus, the inventor realised that targeting such rarer forms would provide for effective treatment, prophylaxis or diagnosis across many human ethnic populations, thereby extending the utility of the present invention.\",\n \"With this realisation, the inventor realised that there is significant industrial and medical application for the invention in terms of guiding the choice of anti-PCSK9 ligand for administration to human patients for therapy and/or prophylaxis of PCSK9-mediated or associated diseases or conditions.\",\n \"In this way, the patient receives drugs and ligands that are tailored to their needs—as determined by the patient's genetic or phenotypic makeup.\",\n \"Hand-in-hand with this, the invention provides for the genotyping and/or phenotyping of patients in connection with such treatment, thereby allowing a proper match of drug to patient.\",\n \"This increases the chances of medical efficacy, reduces the likelihood of inferior treatment using drugs or ligands that are not matched to the patient (eg, poor efficacy and/or side-effects) and avoids pharmaceutical mis-prescription and waste.\",\n \"In developing this thinking, the present inventor decided to determine a set of human PCSK9 variants on the basis of the following criteria, these being criteria that the inventor realised would provide for useful medical drugs and diagnostics to tailored need in the human population.\",\n \"The inventor selected variants having at least 3 of the 4 following criteria:— PCSK9 variants having a cumulative human allele frequency in the range from 1 to 10%; PCSK9 variants having a total human genotype frequency in the range from 1 to about 15%; PCSK9 variants found in many different human ethnic populations (using the standard categorisation of the 1000 Genomes Project, which is an accepted standard in the art; see Table 4 below); and PCSK9 variants found in many individuals distributed across such many different ethnic populations.\",\n \"On the basis of these criteria, the inventor identified the variants listed in Table 1 below (excluding form a).\",\n \"The inventor's selection included, as a consideration, selection for nucleotide variation that produced amino acid variation in corresponding PCSK9 forms (ie, non-synonymous variations), as opposed to silent variations that do not alter amino acid residues in the target protein.\",\n \"TABLE 1 Human PCSK9 variants distributed over several human ethnic populations & having a total human genotype frequency in the range of 1 to about 15% (a) Amino acid variability, population distributions and frequencies ASW, YRI, GBR, 0.4506 TSI, CLM, CHB, (0.8457) LWK, CHS, MXL, Hom JPT, PUR, IBS, FIN, Freq4 Form a 46R 53A 425N 443A 474I 619Q 670E CEU 939 14 (Het + Variant Amino Acid Position & Variation Human No.\",\n \"No.\",\n \"Unique 0.3951 Hom 0.64815 Form 46L 53V 425S 443T 474V 619P 670G Populations Individs1 Pops2 Het Freq3 freq5) Cum Freq6 f x ASW, YRI, GBR, 180 12 0.153 0.009 0.0855 TSI, CLM, LWK, MXL, (0.162) JPT, PUR, IBS, FIN, CEU c x ASW, YRI, GBR, 153 12 0.1296 0.0081 0.0729 TSI, CLM, CHB, (0.1377) LWK, CHS, JPT, PUR, FIN, CEU r x x 0.0234 0.009 0.0292 (0.0324) p x x ASW, GBR, TSI, 49 9 0.0441 (0.0441) 0.0221 CLM, JPT, PUR, IBS, FIN, CEU m x LWK, ASW, YRI, 29 4 0.0225 (0.0225) 0.0149 CLM e x x LWK, ASW, YRI 15 3 0.0135 (0.0135) 0.0068 h x x LWK, ASW, YRI 10 3 0.009 (0.009) 0.0045 aj X x PUR, TSI, FIN, CEU 9 4 0.0081 (0.0081) 0.0041 q x x CHS, ASW, JPT, 7 5 0.0063 (0.0063) 0.0032 PUR, CHB Table Footnotes: “x” in a box indicates that the amino acid for the variant form is different from the amino acid at that position in form a, the variant amino acid being shown in “Amino Acid Position & Variation” of the table and the form a amino acid being shown in the first row of the table; amino acids at all other positions of each variant form are identical to those found in form a. Amino acid numbering is per the numbering shown for the pro-form in Table 2 below.\",\n \"1Number of individuals in 1000 Genomes database found to have the allele; 2Number of unique human ethnic populations in 1000 Genomes database in which the allele was found to occur; 3Heterozygous human genotype frequency, ie, cumulative frequency of all genotypes having one occurrence of the variant allele and one occurrence of another allele (heterozygous state), eg, ac genotype in 1000 Genomes database; 4Homozygous human genotype frequency, ie, cumulative frequency of two occurrences of the variant allele (homozygous state), eg, cc genotype in 1000 Genomes database; and 5Total human genotype frequency, ie, total of heterozygous plus homozygous human genotype frequencies.\",\n \"6Cumulative human allele frequency of all occurrences of the variant allele in 1000 Genomes database.\",\n \"Form a′ is identical to form a with the exception that form a′ has a glycine (G) at position 620 (see US20120093818 (Amgen, Inc)); form a has E at this position.\",\n \"(b) Nucleotide Sequence Variations of Selected Alleles Allele a G C A G A A A Nucleotide Position1 1:55505647 1:55505668 1:55523802 1:55523855 1:55524237 1:55527222 1:55529187 Non-Synonymous Nucleotide Variation2 T T G A G C G Variant ID3 rs11591147 rs11583680 rs28362261 rs28362263 rs562556 rs28362277 rs505151 Corresponding Amino Acid Variation Variant Allele 46L 53V 425S 443T 474V 619P 670G f X c X r X X p X X m X e X X h X X aj X X q X X “x” in a box indicates that a variant allele comprises the non-synonymous nucleotide variation indicated in the 5th row.\",\n \"Table Footnotes: 1Notation is chromosome number (all positions are on human chromosome 1): coordinate number (Ensembl release 73 - September 2013, Genome assembly: GRCh37 (GCA_000001405.13); 2Nucleotide change (compared to allele a nucleotide shown in first row) giving rise to an amino acid change in the variant form (compared to amino acid of allele a); and 3NCBI dbSNP reference number (NCBI dbSNP Build 138 released on Apr.\",\n \"25, 2013).\",\n \"TABLE 2 Sequences (a) Human PCSK9 Form a Amino Acid Sequence (SEQ ID NO: 1) - “Pro-form” with Signal Sequence 46 53 MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP WRLPGTYVVVLKEETHLSQSERTARRLQAQPARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtligleffirksqlvqpvgplvvllplaggysrvlnascqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgedilgassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ Italics = signal sequence 1-30 Courier = pro peptide 31-152 lower case = catalytic domain 153-449 UPPER CASE = C-terminal domain 450-692 Underlined = residues changed from allele a in other sequences (aa residue number shown) The pro-form is the sequence from amino acid number 31 to (and including) amino acid number 692 of SEQ ID NO: 1.The mature form is the sequence from amino acid number 153 to (and including) amino acid number 692 of SEQ ID NO: 12 (b) Human PCSK9 Form α Amino Acid Sequence (SEQ ID NO: 3) - “Mature-form” (Numbering and notation as per SEQ ID NO: 1 above has been retained) sipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvinaacqrlaragvvlvtaagnfrddady spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqlihfsak 425 443 474 dvineawfpedqrvtpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ (c) Human PCSK9 Allele a Nucleotide Sequence (SEQ ID NO: 28) - Encoding “Pro-form” Plus Signal Sequence ATGGGCACCGTCAGCTCCAGGCGGTCCTGGTGGCCGCTGCCACTGCTGCTGCTGCTGCTGCTGCTCCTGGGTC R46L CGT to CTT CCGCGGGCGCCCGTGCGCAGGAGGACGAGGACGGCGACTACGAGGAGCTGGTGCTAGCCTTGCGTTCCG A53V GCC to GTC AGGAGGACGGCCTGGCCGAAGCACCCGAGCACGGAACCACAGCCACCTTCCACCGCTGCGCCAAGGAT CCGTGGAGGTTGCCTGGCACCTACGTGGTGGTGCTGAAGGAGGAGACCCACCTCTCGCAGTCAGAGCG CACTCCCCGCCGCCTGCAGGCCCAGGCTGCCCGCCGGGGATACCTCACCAAGATCCTGCATGTCTTCC ATGGCCTTCTTCCTGGCTTCCTGGTGAAGATGAGTGGCGACCTGCTGGAGTGGCCTTGAAGTTGCCC CATGTCGACTACATCGAGGAGGACTCCTCTGTCTTTGCCCAGagcattcccgtggaacctggagcggattacccctcca cggtaccgggcggatgaataccagccccccgacggaggcagcctggtggaggtgtatctcctagacaccagcatacagagtgaccaccgggaa atcgagggcagggtcatggtcaccgacttcgagaatgtgcccgaggaggacgggacccgcttccacagacaggccagcaagtgtgacagtcat ggcacccacctggcaggggtggtcagcggccgggatgccggcgtggccaagggtgccagcatgcgcagcctgcgcgtgctcaactgccaaggg aagggcacggttagcggcaccctcataggcctggagtttattcggaaaagccagctggtccagcctgtggggccactggtggtgctgctgcccct ggcgggtgggtacagccgcgtcctcaacgccgcctgccagcgcctggcgagggctggggtcgtgctggtcaccgctgccggcaacttccgggac gatgcctgcctctactccccagcctcagctcccgaggtcatcacagttggggccaccaatgcccaagaccagccggtgaccctggggactttggg gaccaactttggccgctgtgtggacctctttgccccaggggaggacatcattggtgcctccagcgactgcagcacctgctttgtgtcacagagtgg gacatcacaggctgctgcccacgtggctggcattgcagccatgatgctgtctgccgagccggagctcaccctggccgagttgaggcagagactg N425s AAT to AGT A443T GCC to ACC atccacttctctgccaaagatgtcatcaatgaggcctggttccctgaggaccagcgggtactgacccccacctggtggccgccctgccccccag caccatGGGGCAGGTTGGCAGCTGTTTTGCAGGACTGTATGGTCAGCACACTCGGGGCCTACACGGATGGCC I474V ATC to GTC ACAGCCATCGCCCGCTGCGCCCCAGATGAGGAGCTGCTGAGCTGCTCCAGTTTCTCCAGGAGTGGGAAGCGG CGGGGCGAGCGCATGGAGGCCCAAGGGGGCAAGCTGGTCTGCCGGGCCCACAACGCTTTTGGGGGTGAGG GTGTCTACGCCATTGCCAGGTGCTGCCTGCTACCCCAGGCCAACTGCAGCGTCCACACAGCTCCACCAGCTGA GGCCAGCATGGGGACCCGTGTCCACTGCCACCAACAGGGCCACGTCCTCACAGGCTGCAGCTCCCACTGGGA GGTGGAGGACCTTGGCACCCACAAGCCGCCTGTGCTGAGGCCACGAGGTCAGCCCAACCAGTGCGTGGGCC ACAGGGAGGCCAGCATCCACGCTTCCTGCTGCCATGCCCCAGGTCTGGAATGCAAAGTCAAGGAGCATGGAA Q619P CAG to CCG E620G GAG to GGG TCCCGGCCCCTCAGGAGCAGGTGACCGTGGCCTGCGAGGAGGGCTGGACCCTGACTGGCTGCAGTGCCCTCC CTGGGACCTCCCACGTCCTGGGGGCCTACGCCGTAGACAACACGTGTGTAGTCAGGAGCCGGGACGTCAGCA E670G GAG to GGG CTACAGGCAGCACCAGCGAAGAGGCCGTGACAGCCGTTGCCATCTGCTGCCGGAGCCGGCACCTGGCGCAG GCCTCCCAGGAGCTCCAGTGAC Italics = nucleotide sequence encoding signal sequence (nucleotides 1-90) Courier = nucleotide sequence encoding pro peptide (nucleotides 91-456) lower case = nucleotide sequence encoding catalytic domain (nucleotides 457-1346) UPPER CASE = nucleotide sequence encoding C-terminal domain (nucleotides 1347-2076) Underlined = allelic variations from allele a in other sequences (aa residue number changes and codon changes shown) The pro-form is encoded by nucleotide sequence from nucleotide 91 to (and including) nucleotide 2076.The mature form is encoded by nucleotide sequence from nucleotide 457 to (and including) nucleotide 2076.Variant Allele Nucleotide Sequences Thus, (i) The nucleotide sequence of allele f is identical to SEQ ID NO: 28 except that the nucleotide sequence of allele f comprises a GTC codon instead of an ATC codon at the position labelled “I474V” in SEQ ID NO: 28; (ii) The nucleotide sequence of allele c is identical to SEQ ID NO: 28 except that the nucleotide sequence of allele c comprises a GGG codon instead of an GAG codon at the position labelled “E670G” in SEQ ID NO: 28; (iii) The nucleotide sequence of allele r is identical to SEQ ID NO: 28 except that the nucleotide sequence of allele r comprises a GTC codon instead of an ATC codon at the position labelled “I474V” in SEQ ID NO: 28; and a GGG codon instead of an GAG codon at the position labelled “E670G” in SEQ ID NO: 28; (iv) The nucleotide sequence of allele p is identical to SEQ ID NO: 28 except that the nucleotide sequence of allele p comprises a GTC codon instead of a GCC codon at the position labelled “A53V” in SEQ ID NO: 28; and a GTC codon instead of an ATC codon at the position labelled “I474V” in SEQ ID NO: 28; (v) The nucleotide sequence of allele m is identical to SEQ ID NO: 28 except that the nucleotide sequence of allele m comprises a ACC codon instead of a GCC codon at the position labelled “A443T” in SEQ ID NO: 28; (vi) The nucleotide sequence of allele e is identical to SEQ ID NO: 28 except that the nucleotide sequence of allele e comprises a AGT codon instead of an AAT codon at the position labelled “N425S” in SEQ ID NO: 28; and a GTC codon instead of an ATC codon at the position labelled “I474V” in SEQ ID NO: 28; (vii) The nucleotide sequence of allele h is identical to SEQ ID NO: 28 except that the nucleotide sequence of allele h comprises a ACC codon instead of a GCC codon at the position labelled “A443T” in SEQ ID NO: 28; and a CCG codon instead of a CAG codon at the position labelled “Q619P” in SEQ ID NO: 28; (viii) The nucleotide sequence of allele aj is identical to SEQ ID NO: 28 except that the nucleotide sequence of allele aj comprises a CTT codon instead of an CGT codon at the position labelled “R46L” in SEQ ID NO: 28; and a GTC codon instead of an ATC codon at the position labelled “I474V” in SEQ ID NO: 28; and (ix) The nucleotide sequence of allele q is identical to SEQ ID NO: 28 except that the nucleotide sequence of allele q comprises a GTC codon instead of a GCC codon at the position labelled “A53V” in SEQ ID NO: 28; and a GGG codon instead of an GAG codon at the position labelled “E670G” in SEQ ID NO: 28.Variant Pro-Form Amino Acid Sequences (Numbering is as per SEQ ID NO: 1 recited above) (A) The amino acid sequence of form f is identical to the amino acid sequence from amino acid number 31 to (and including) amino acid number 692 of SEQ ID NO: 1 except that the amino acid sequence of form f comprises a valine at position 474; (B) The amino acid sequence of form c is identical to the amino acid sequence from amino acid number 31 to (and including) amino acid number 692 of SEQ ID NO: 1 except that the amino acid sequence of form c comprises a glycine at position 670; (C) The amino acid sequence of form r is identical to the amino acid sequence from amino acid number 31 to (and including) amino acid number 692 of SEQ ID NO: 1 except that the amino acid sequence of form r comprises a valine at position 474 and a glycine at position 670; (D) The amino acid sequence of form p is identical the amino acid sequence from amino acid number 31 to (and including) amino acid number 692 of SEQ ID NO: 1 except that the amino acid sequence of form p comprises a valine at position 53 and a valine at position 474; (E) The amino acid sequence of form m is identical to the amino acid sequence from amino acid number 31 to (and including) amino acid number 692 of SEQ ID NO: 1 except that the amino acid sequence of form m comprises a threonine at position 443; (F) The amino acid sequence of form e is identical to the amino acid sequence from amino acid number 31 to (and including) amino acid number 692 of SEQ ID NO: 1 except that the amino acid sequence of form e comprises a serine at position 425 and a valine at position 474; (G) The amino acid sequence of form h is identical to the amino acid sequence from amino acid number 31 to (and including) amino acid number 692 of SEQ ID NO: 1 except that the amino acid sequence of form h comprises a threonine at position 443 and a proline at position 619; (H) The amino acid sequence of form aj is identical to the amino acid sequence from amino acid number 31 to (and including) amino acid number 692 of SEQ ID NO: 1 except that the amino acid sequence of form aj comprises a leucine at position 46 and a valine at position 474; and (I) The amino acid sequence of form q is identical to the amino acid sequence from amino acid number 31 to (and including) amino acid number 692 of SEQ ID NO: 1 except that the amino acid sequence of form q comprises a valine at position 53 and a glycine at position 670.Variant Mature Form Amino Acid Sequences (Numbering is as per SEQ ID NO: 1 recited above) (A′) The amino acid sequence of form f is identical to SEQ ID NO: 2 except that the amino acid sequence of form f comprises a valine at position 474; (B′) The amino acid sequence of form c is identical to SEQ ID NO: 2 except that the amino acid sequence of form c comprises a glycine at position 670; (C′) The amino acid sequence of form r is identical to SEQ ID NO: 2 except that the amino acid sequence of form r comprises a valine at position 474 and a glycine at position 670; (D′) The amino acid sequence of form p is identical to SEQ ID NO: 2 except that the amino acid sequence of form p comprises a valine at position 474; (E′) The amino acid sequence of form m is identical to SEQ ID NO: 2 except that the amino acid sequence of form m comprises a threonine at position 443; (F′) The amino acid sequence of form e is identical to SEQ ID NO: 2 except that the amino acid sequence of form e comprises a serine at position 425 and a valine at position 474; (G′) The amino acid sequence of form h is identical to SEQ ID NO: 2 except that the amino acid sequence of form h comprises a threonine at position 443 and a proline at position 619; (H′) The amino acid sequence of form aj is identical to SEQ ID NO: 2 except that the amino acid sequence of form aj comprises valine at position 474; and (I′) The amino acid sequence of form q is identical to SEQ ID NO: 2 except that the amino acid sequence of form q comprises a glycine at position 670.The mature form of p is identical to the mature form off and aj.\",\n \"The mature form of c is identical to the mature form of q.\",\n \"Further sequence analysis and 3D in silico modelling (see FIG.\",\n \"1) revealed that selected variants also fulfilled the following selection criteria:— PCSK9 variants whose variant amino acid residues (versus the common form of human PCSK9) are found in the mature form of the target (ie, outside the pro-domain); and PCSK9 variants whose variant amino acid residues (versus the common form of human PCSK9) are surface-exposed on the target, which the inventor saw as contributing to determining the topography of the target and potentially contributing to how and where ligand binding on the target occurs.\",\n \"As shown in FIG.\",\n \"1, identified positions 425, 443, 474, 619 and 670 (found in the selected variants of the invention) are all surface-exposed and outside of the pro-domain.\",\n \"Variant positions 425 and 443 are surface-exposed on the catalytic domain, while variant positions 474, 619 and 670 are surface-exposed on the C-terminal domain.\",\n \"In a first example, the invention addresses the need to treat humans having naturally-occurring rarer natural PCSK9 alleles, genotypes and phenotypes (rarer protein forms).\",\n \"In this respect, the invention provides the following aspects: In a First Aspect: An anti-human PCSK9 ligand for use in a method of treating and/or preventing a PCSK9-mediated disease or condition in a human whose genome comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37, wherein the method comprises administering the ligand to the human.\",\n \"In an example, the nucleotide sequence is selected from the group consisting of SEQ ID NOs: 29-35 and 37; or selected from the group consisting of SEQ ID NOs: 29-32 and 34-37; or selected from the group consisting of SEQ ID NOs: 29-32, 34, 35 and 37.These are naturally-occurring allele (haplotype) sequences that do not encode 46L and which meet the criteria set out above.\",\n \"These groups comprise variants that are associated with elevated LDL-C.\",\n \"In an example, the nucleotide sequence is SEQ ID NO: 34, that encodes a 425S, which is associated with elevated LDL-C (Pisciotta et al 2006).\",\n \"In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31 and 37, that encode 670G which is a marker for severity of coronary atherosclerosis (Chen et al 2005).\",\n \"In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35, 36 and 37; or selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35 and 37.These are allele (haplotype) sequences that have a naturally-occurring combination of differences from SEQ ID NO: 28 (form a) and which meet the criteria set out above.\",\n \"In an example, the nucleotide sequence is SEQ ID NO: 29.In an example, the nucleotide sequence is SEQ ID NO: 30.In an example, the nucleotide sequence is SEQ ID NO: 31.In an example, the nucleotide sequence is SEQ ID NO: 32.In an example, the nucleotide sequence is SEQ ID NO: 33.In an example, the nucleotide sequence is SEQ ID NO: 34.In an example, the nucleotide sequence is SEQ ID NO: 35.In an example, the nucleotide sequence is SEQ ID NO: 36.In an example, the nucleotide sequence is SEQ ID NO: 37.In a Second Aspect: The ligand of aspect 1, wherein the ligand has been or is determined as capable of binding a human PCSK9 selected from the group consisting forms f, c, r, p, m, e, h, aj and q.\",\n \"In an example of any aspect, the ligand binds (or has been determined to bind) two, three, four or more human PCSK9 selected from the group consisting forms f, c, r, p, m, e, h, aj and q.\",\n \"In an example of any aspect, the ligand comprises a protein domain that specifically binds to PCSK9, eg, a human PCSK9 selected from the group consisting forms f, c, r, p, m, e, h, aj and q.\",\n \"The term “specifically binds,” or the like, means that a ligand, eg, an antibody or antigen-binding fragment thereof, forms a complex with an antigen that is relatively stable under physiologic conditions.\",\n \"Specific binding can be characterized by an equilibrium dissociation constant of at least about 1×10−6 M or less (e.g., a smaller KD denotes a tighter binding).\",\n \"Methods for determining whether two molecules specifically bind are well known in the art and include, for example, equilibrium dialysis, surface plasmon resonance, and the like.\",\n \"An isolated antibody that specifically binds a human PCSK9 may, however, exhibit cross-reactivity to other antigens such as a PCSK9 molecule from another specie.\",\n \"Moreover, multi-specific antibodies (e.g., bispecifics) that bind to human PCSK9 and one or more additional antigens are nonetheless considered antibodies that “specifically bind” PCSK9, as used herein.\",\n \"In an example of any aspect, the ligand comprises or consists of a protein that mimics the EGFA domain of the LDL receptor and specifically binds to PCSK9, eg, a human PCSK9 selected from the group consisting forms f, c, r, p, m, e, h, aj and q.\",\n \"In an example of any aspect, the ligand antagonises PCSK9, eg, a human PCSK9 selected from the group consisting forms f, c, r, p, m, e, h, aj and q.\",\n \"In an example of any aspect, the method comprises (before administering the ligand) the step of determining that the ligand is capable of binding a human PCSK9 selected from the group consisting forms f, c, r, p, m, e, h, aj and q.\",\n \"In an example of any aspect, binding is determined by SPR.\",\n \"In an example of any aspect, binding is determined by ELISA.\",\n \"In an example of any aspect, said forms are the mature forms.\",\n \"In an example of any aspect, said forms are the pro-forms.\",\n \"In a Third Aspect: A ligand that binds a human PCSK9 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 4-27 for use in a method comprising the step of using the ligand to target said PCSK9 in a human to treat and/or prevent a disease or condition mediated by PCSK9, the method comprising administering the ligand to the human.\",\n \"In an example, the disease or condition is mediated by a human PCSK9 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 4-27.In an example, the amino acid sequence selected from the group consisting of SEQ ID NOs: 4-23, 26 and 27; or selected from the group consisting of SEQ ID NOs: 4-14 and 18-27; or selected from the group consisting of SEQ ID NOs: 4-14, 18-23, 26 and 27.These are naturally-occurring sequences that do not comprise 46L and which meet the criteria set out above.\",\n \"These groups comprise variants that are associated with elevated LDL-C.\",\n \"In an example, the amino acid sequence is SEQ ID NO: 18, 19 or 20, that comprises a 425S, which is associated with elevated LDL-C (Pisciotta et al 2006).\",\n \"In an example, the amino acid sequence selected from the group consisting of SEQ ID NOs: 10, 11, 12, 26 and 27, that comprise 670G which is a marker for severity of coronary atherosclerosis (Chen et al 2005).\",\n \"In an example, the amino acid sequence selected from the group consisting of SEQ ID NOs: 10-14 and 18-27; or selected from the group consisting of SEQ ID NOs: 10-14, 18-23, 26 and 27.These are sequences that have a naturally-occurring combination of differences from SEQ ID NOs: 1-3 (form a) and which meet the criteria set out above.\",\n \"In an example, the amino acid sequence is SEQ ID NO: 4.In an example, the amino acid sequence is SEQ ID NO: 5.In an example, the amino acid sequence is SEQ ID NO: 6.In an example, the amino acid sequence is SEQ ID NO: 7.In an example, the amino acid sequence is SEQ ID NO: 8.In an example, the amino acid sequence is SEQ ID NO: 9.In an example, the amino acid sequence is SEQ ID NO: 10.In an example, the amino acid sequence is SEQ ID NO: 11.In an example, the amino acid sequence is SEQ ID NO: 12.In an example, the amino acid sequence is SEQ ID NO: 13.In an example, the amino acid sequence is SEQ ID NO: 14.In an example, the amino acid sequence is SEQ ID NO: 15.In an example, the amino acid sequence is SEQ ID NO: 16.In an example, the amino acid sequence is SEQ ID NO: 17.In an example, the amino acid sequence is SEQ ID NO: 18.In an example, the amino acid sequence is SEQ ID NO: 19.In an example, the amino acid sequence is SEQ ID NO: 20.In an example, the amino acid sequence is SEQ ID NO: 21.In an example, the amino acid sequence is SEQ ID NO: 22.In an example, the amino acid sequence is SEQ ID NO: 23.In an example, the amino acid sequence is SEQ ID NO: 24.In an example, the amino acid sequence is SEQ ID NO: 25.In an example, the amino acid sequence is SEQ ID NO: 26.In an example, the amino acid sequence is SEQ ID NO: 27.In a Fourth Aspect: The ligand of aspect 3, wherein the genome of the human comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37.In an example, the nucleotide sequence is selected from the group consisting of SEQ ID NOs: 29-35 and 37; or selected from the group consisting of SEQ ID NOs: 29-32 and 34-37; or selected from the group consisting of SEQ ID NOs: 29-32, 34, 35 and 37.These are naturally-occurring allele (haplotype) sequences that do not encode 46L and which meet the criteria set out above.\",\n \"These groups comprise variants that are associated with elevated LDL-C.\",\n \"In an example, the nucleotide sequence is SEQ ID NO: 34, that encodes a 425S, which is associated with elevated LDL-C (Pisciotta et al 2006).\",\n \"In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31 and 37, that encode 670G which is a marker for severity of coronary atherosclerosis (Chen et al 2005).\",\n \"In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35, 36 and 37; or selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35 and 37.These are allele (haplotype) sequences that have a naturally-occurring combination of differences from SEQ ID NO: 28 (form a) and which meet the criteria set out above.\",\n \"In an example, the nucleotide sequence is SEQ ID NO: 29 In an example, the nucleotide sequence is SEQ ID NO: 30.In an example, the nucleotide sequence is SEQ ID NO: 31.In an example, the nucleotide sequence is SEQ ID NO: 32.In an example, the nucleotide sequence is SEQ ID NO: 33 In an example, the nucleotide sequence is SEQ ID NO: 34 In an example, the nucleotide sequence is SEQ ID NO: 35.In an example, the nucleotide sequence is SEQ ID NO: 36.In an example, the nucleotide sequence is SEQ ID NO: 37.In a Fifth Aspect: The ligand of any preceding aspect, wherein the human has been or is genotyped as positive for a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof.\",\n \"In an example, the nucleotide sequence is selected from the group consisting of SEQ ID NOs: 29-35 and 37; or selected from the group consisting of SEQ ID NOs: 29-32 and 34-37; or selected from the group consisting of SEQ ID NOs: 29-32, 34, 35 and 37.These are naturally-occurring allele (haplotype) sequences that do not encode 46L and which meet the criteria set out above.\",\n \"These groups comprise variants that are associated with elevated LDL-C.\",\n \"In an example, the nucleotide sequence is SEQ ID NO: 34, that encodes a 425S, which is associated with elevated LDL-C (Pisciotta et al 2006).\",\n \"In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31 and 37, that encode 670G which is a marker for severity of coronary atherosclerosis (Chen et al 2005).\",\n \"In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35, 36 and 37; or selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35 and 37.These are allele (haplotype) sequences that have a naturally-occurring combination of differences from SEQ ID NO: 28 (form a) and which meet the criteria set out above.\",\n \"In an example, the nucleotide sequence is SEQ ID NO: 29.In an example, the nucleotide sequence is SEQ ID NO: 30.In an example, the nucleotide sequence is SEQ ID NO: 31.In an example, the nucleotide sequence is SEQ ID NO: 32.In an example, the nucleotide sequence is SEQ ID NO: 33.In an example, the nucleotide sequence is SEQ ID NO: 34.In an example, the nucleotide sequence is SEQ ID NO: 35.In an example, the nucleotide sequence is SEQ ID NO: 36.In an example, the nucleotide sequence is SEQ ID NO: 37.In a Sixth Aspect: The ligand of any preceding aspect, wherein the human has been or is phenotyped as positive for a human PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q or at least the catalytic or C-terminal domain thereof.\",\n \"In an example, said forms are the mature forms.\",\n \"In an example, said forms are the pro-forms.\",\n \"In a Seventh Aspect: The ligand of any preceding aspect, wherein the method comprises genotyping the human as positive for a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof.\",\n \"In an example, the nucleotide sequence is selected from the group consisting of SEQ ID NOs: 29-35 and 37; or selected from the group consisting of SEQ ID NOs: 29-32 and 34-37; or selected from the group consisting of SEQ ID NOs: 29-32, 34, 35 and 37.These are naturally-occurring allele (haplotype) sequences that do not encode 46L and which meet the criteria set out above.\",\n \"These groups comprise variants that are associated with elevated LDL-C.\",\n \"In an example, the nucleotide sequence is SEQ ID NO: 34, that encodes a 425S, which is associated with elevated LDL-C (Pisciotta et al 2006).\",\n \"In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31 and 37, that encode 670G which is a marker for severity of coronary atherosclerosis (Chen et al 2005).\",\n \"In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35, 36 and 37; or selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35 and 37.These are allele (haplotype) sequences that have a naturally-occurring combination of differences from SEQ ID NO: 28 (form a) and which meet the criteria set out above.\",\n \"In an example, the nucleotide sequence is SEQ ID NO: 29.In an example, the nucleotide sequence is SEQ ID NO: 30.In an example, the nucleotide sequence is SEQ ID NO: 31.In an example, the nucleotide sequence is SEQ ID NO: 32.In an example, the nucleotide sequence is SEQ ID NO: 33.In an example, the nucleotide sequence is SEQ ID NO: 34.In an example, the nucleotide sequence is SEQ ID NO: 35.In an example, the nucleotide sequence is SEQ ID NO: 36.In an example, the nucleotide sequence is SEQ ID NO: 37.In an Eighth Aspect: The ligand of any preceding aspect, wherein the method comprises phenotyping the human has positive for a human PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q or at least the catalytic or C-terminal domain thereof.\",\n \"In an example, said forms are the mature forms.\",\n \"In an example, said forms are the pro-forms.\",\n \"In a Ninth Aspect: The ligand of any preceding aspect, wherein the human has been or is genotyped as heterozygous for a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof, optionally wherein the human has been or is genotyped as comprising the nucleotide sequence of SEQ ID NO: 28 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof and a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof.\",\n \"“Heterozygous” here means that in the human's genotype one allele comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof and other allele can be any PCSK9 (eg, form a, a′ or an allele comprising a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof).\",\n \"In an example, the method comprises (before administering the ligand) genotyping the human as heterozygous for a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof, optionally also genotyping the human as comprising the nucleotide sequence of SEQ ID NO: 28 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof and a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof.\",\n \"In an example, the nucleotide sequence is selected from the group consisting of SEQ ID NOs: 29-35 and 37; or selected from the group consisting of SEQ ID NOs: 29-32 and 34-37; or selected from the group consisting of SEQ ID NOs: 29-32, 34, 35 and 37.These are naturally-occurring allele (haplotype) sequences that do not encode 46L and which meet the criteria set out above.\",\n \"These groups comprise variants that are associated with elevated LDL-C.\",\n \"In an example, the nucleotide sequence is SEQ ID NO: 34, that encodes a 425S, which is associated with elevated LDL-C (Pisciotta et al 2006).\",\n \"In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31 and 37, that encode 670G which is a marker for severity of coronary atherosclerosis (Chen et al 2005).\",\n \"In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35, 36 and 37; or selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35 and 37.These are allele (haplotype) sequences that have a naturally-occurring combination of differences from SEQ ID NO: 28 (form a) and which meet the criteria set out above.\",\n \"In an example, the nucleotide sequence is SEQ ID NO: 29.In an example, the nucleotide sequence is SEQ ID NO: 30.In an example, the nucleotide sequence is SEQ ID NO: 31.In an example, the nucleotide sequence is SEQ ID NO: 32.In an example, the nucleotide sequence is SEQ ID NO: 33.In an example, the nucleotide sequence is SEQ ID NO: 34.In an example, the nucleotide sequence is SEQ ID NO: 35.In an example, the nucleotide sequence is SEQ ID NO: 36.In an example, the nucleotide sequence is SEQ ID NO: 37.In a Tenth Aspect: The ligand of any one of aspects 1 to 9, wherein the genome of the human has been or is genotyped as homozygous for a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof.\",\n \"“Homozygous” here means that in the human's genotype each allele comprises the same nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof.\",\n \"In an example, the method comprises genotyping the human as homozygous for a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof.\",\n \"In an example, the nucleotide sequence is selected from the group consisting of SEQ ID NOs: 29-35 and 37; or selected from the group consisting of SEQ ID NOs: 29-32 and 34-37; or selected from the group consisting of SEQ ID NOs: 29-32, 34, 35 and 37.These are naturally-occurring allele (haplotype) sequences that do not encode 46L and which meet the criteria set out above.\",\n \"These groups comprise variants that are associated with elevated LDL-C.\",\n \"In an example, the nucleotide sequence is SEQ ID NO: 34, that encodes a 425S, which is associated with elevated LDL-C (Pisciotta et al 2006).\",\n \"In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31 and 37, that encode 670G which is a marker for severity of coronary atherosclerosis (Chen et al 2005).\",\n \"In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35, 36 and 37; or selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35 and 37.These are allele (haplotype) sequences that have a naturally-occurring combination of differences from SEQ ID NO: 28 (form a) and which meet the criteria set out above.\",\n \"In an example, the nucleotide sequence is SEQ ID NO: 29.In an example, the nucleotide sequence is SEQ ID NO: 30.In an example, the nucleotide sequence is SEQ ID NO: 31.In an example, the nucleotide sequence is SEQ ID NO: 32.In an example, the nucleotide sequence is SEQ ID NO: 33.In an example, the nucleotide sequence is SEQ ID NO: 34.In an example, the nucleotide sequence is SEQ ID NO: 35.In an example, the nucleotide sequence is SEQ ID NO: 36.In an example, the nucleotide sequence is SEQ ID NO: 37.In an Eleventh Aspect: The ligand of any preceding aspect, wherein the ligand comprises an antibody binding site that binds a human PCSK9 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 4-27 and optionally has been or is determined as capable of such binding.\",\n \"In an example, the method comprises (before administering the ligand) the step of determining that the ligand is capable of binding to said human PCSK9.In an example, the binding is specific binding.\",\n \"In an example, the ligand binds (or has been determined as binding) to the PCSK9 with an affinity (Kd) of 1 mM, 100 nM, 10 nM or 1 nM or less.\",\n \"In an embodiment, the affinity is no less than 10, 100 or 1000 fM.\",\n \"In an example, binding or affinity is determined by SPR or ELISA.\",\n \"In an example, the disease or condition is mediated by a human PCSK9 comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 4-27.In an example, the amino acid sequence selected from the group consisting of SEQ ID NOs: 4-23, 26 and 27; or selected from the group consisting of SEQ ID NOs: 4-14 and 18-27; or selected from the group consisting of SEQ ID NOs: 4-14, 18-23, 26 and 27.These are naturally-occurring sequences that do not comprise 46L and which meet the criteria set out above.\",\n \"These groups comprise variants that are associated with elevated LDL-C.\",\n \"In an example, the amino acid sequence is SEQ ID NO: 18, 19 or 20, that comprises a 425S, which is associated with elevated LDL-C (Pisciotta et al 2006).\",\n \"In an example, the amino acid sequence selected from the group consisting of SEQ ID NOs: 10, 11, 12, 26 and 27, that comprise 670G which is a marker for severity of coronary atherosclerosis (Chen et al 2005).\",\n \"In an example, the amino acid sequence selected from the group consisting of SEQ ID NOs: 10-14 and 18-27; or selected from the group consisting of SEQ ID NOs: 10-14, 18-23, 26 and 27.These are sequences that have a naturally-occurring combination of differences from SEQ ID NOs: 1-3 (form a) and which meet the criteria set out above In an example, the amino acid sequence is SEQ ID NO: 4.In an example, the amino acid sequence is SEQ ID NO: 5.In an example, the amino acid sequence is SEQ ID NO: 6.In an example, the amino acid sequence is SEQ ID NO: 7.In an example, the amino acid sequence is SEQ ID NO: 8.In an example, the amino acid sequence is SEQ ID NO: 9.In an example, the amino acid sequence is SEQ ID NO: 10.In an example, the amino acid sequence is SEQ ID NO: 11.In an example, the amino acid sequence is SEQ ID NO: 12.In an example, the amino acid sequence is SEQ ID NO: 13.In an example, the amino acid sequence is SEQ ID NO: 14.In an example, the amino acid sequence is SEQ ID NO: 15.In an example, the amino acid sequence is SEQ ID NO: 16.In an example, the amino acid sequence is SEQ ID NO: 17.In an example, the amino acid sequence is SEQ ID NO: 18.In an example, the amino acid sequence is SEQ ID NO: 19.In an example, the amino acid sequence is SEQ ID NO: 20.In an example, the amino acid sequence is SEQ ID NO: 21.In an example, the amino acid sequence is SEQ ID NO: 22.In an example, the amino acid sequence is SEQ ID NO: 23.In an example, the amino acid sequence is SEQ ID NO: 24.In an example, the amino acid sequence is SEQ ID NO: 25.In an example, the amino acid sequence is SEQ ID NO: 26.In an example, the amino acid sequence is SEQ ID NO: 27.In a Twelfth Aspect: The ligand of aspect 11, wherein the ligand is an antibody or antibody fragment.\",\n \"For example, the antibody or antibody fragment is a PCSK9 antagonist, eg, neutralises PCSK9.Examples of such antibodies are disclosed, for instance, in WO 2008/057457, WO2008/057458, WO 2008/057459, WO 2008/063382, WO 2008/133647, WO 2009/100297, WO 2009/100318, WO 2011/037791, WO 2011/053759, WO 2011/053783, WO 2008/125623, WO 2011/072263, WO 2009/055783, WO 2010/029513, WO 2011/111007, WO 2010/077854, the disclosures and sequences of such antibodies being incorporated herein for use in the invention in their entireties by reference.\",\n \"One specific example is AMG 145 (Amgen), LY3015014 (Eli Lilly) or alirocumab.\",\n \"Advantageously, the ligand is or comprises alirocumab.\",\n \"Alternatively, the ligand is or comprises evolocumab.\",\n \"In an example, the ligand is SAR236553/REGN727 (Sanofi Aventis/Regeneron) or a PCSK9-binding derivative thereof.\",\n \"In an example, the ligand comprises or consists of a neutralizing antibody that binds to the PCSK9, wherein the antibody binds to PCSK9 and reduces the likelihood that PCSK9 binds to LDLR.\",\n \"The ligand of aspect 11, wherein the ligand is a PCSK9 antagonist, eg, neutralises PCSK9.In an example of any aspect of the invention, the ligand comprises or consists a ligand selected from evolocumab, 1D05-IgG2 (Merck & Co.), ALN-PCS02 (Alnylam), RN316 (Pfizer-Rinat), LY3015014 (Eli Lilly) and alirocumab (SAR236553/REGN727; Sanofi Aventis/Regeneron).\",\n \"In Thirteenth Aspect: The ligand of any one of aspects 1 to 10, wherein (i) the ligand comprises a sequence of contiguous nucleotides that specifically hybridises to a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof, or specifically hybridises to an antisense sequence or an RNA transcript of said sequence, wherein said sequence of contiguous nucleotides hybridises to at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 or hybridises to an antisense sequence or an RNA transcript thereof respectively; and/or (ii) the ligand comprises a sequence of at least 10 contiguous nucleotides of a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or is an antisense sequence or RNA version of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28.In an example, the nucleotide sequence is selected from the group consisting of SEQ ID NOs: 29-35 and 37; or selected from the group consisting of SEQ ID NOs: 29-32 and 34-37; or selected from the group consisting of SEQ ID NOs: 29-32, 34, 35 and 37.These are naturally-occurring allele (haplotype) sequences that do not encode 46L and which meet the criteria set out above.\",\n \"These groups comprise variants that are associated with elevated LDL-C.\",\n \"In an example, the nucleotide sequence is SEQ ID NO: 34, that encodes a 425S, which is associated with elevated LDL-C (Pisciotta et al 2006).\",\n \"In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31 and 37, that encode 670G which is a marker for severity of coronary atherosclerosis (Chen et al 2005).\",\n \"In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35, 36 and 37; or selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35 and 37.These are allele (haplotype) sequences that have a naturally-occurring combination of differences from SEQ ID NO: 28 (form a) and which meet the criteria set out above.\",\n \"In an example, the nucleotide sequence is SEQ ID NO: 29.In an example, the nucleotide sequence is SEQ ID NO: 30.In an example, the nucleotide sequence is SEQ ID NO: 31.In an example, the nucleotide sequence is SEQ ID NO: 32.In an example, the nucleotide sequence is SEQ ID NO: 33.In an example, the nucleotide sequence is SEQ ID NO: 34.In an example, the nucleotide sequence is SEQ ID NO: 35.In an example, the nucleotide sequence is SEQ ID NO: 36.In an example, the nucleotide sequence is SEQ ID NO: 37.In an embodiment, the ligand comprises at least 10, 11, 12, 13, 14, 15, 20, 25, 30, 35, 40, 45, 50 or 100 contiguous nucleotides of said nucleotide sequence.\",\n \"In a Fourteenth Aspect: The ligand of any preceding aspect, wherein said disease or condition is hyperlipidaemia, hypercholesterolaemia (eg, familial hypercholesterolaemia), heart attack, stroke, coronary heart disease, atherosclerosis or a cardiovascular disease or condition.\",\n \"The ligand of any preceding aspect, wherein the disease or condition is hypercholesterolemia, hyperlipidemia, hypercholesterolemia, dyslipidemia, cholestatic liver disease, nephrotic syndrome, hypothyroidism, obesity, atherosclerosis or a cardiovascular disease.\",\n \"In an example, said disease or condition is hypercholesterolaemia.\",\n \"The term “hypercholesterolaemia,” as used herein, refers to a condition in which cholesterol levels are elevated above a desired level.\",\n \"In some embodiments, this denotes that serum cholesterol levels are elevated.\",\n \"In some embodiments, the desired level takes into account various “risk factors” that are known to one of skill in the art (and are described or referenced in US20120093818).\",\n \"The ligand of any preceding aspect, wherein the human is identified as heterozygous for Familial Hypercholesterolemia, statin intolerant, statin uncontrolled, or at risk for developing hypercholesterolemia, dyslipidemia, cholestatic liver disease, nephrotic syndrome, hypothyroidism, obesity, atherosclerosis or a cardiovascular disease.\",\n \"In a Fifteenth Aspect: The ligand of any preceding aspect, wherein said disease or condition is associated with elevated LDL cholesterol.\",\n \"Cholesterol levels are measured in milligrams (mg) of cholesterol per deciliter (dL) of blood in the United States and some other countries.\",\n \"Canada and most European countries measure cholesterol in millimoles (mmol) per liter (L) of blood.\",\n \"Below are general guideline ideal ranges and elevated ranges.\",\n \"Total cholesterol* Total cholesterol (Canada and (U.S. and some other countries) most of Europe) Below 200 mg/dL Below 5.2 mmol/L Ideal 200-239 mg/dL 5.2-6.2 mmol/L Borderline high 240 mg/dL and above Above 6.2 mmol/L High LDL cholesterol* LDL cholesterol (Canada and (U.S. and some other countries) most of Europe) 100-129 mg/dL 2.6-3.3 mmol/L Ideal 130-159 mg/dL 3.4-4.1 mmol/L Borderline high 160-189 mg/dL 4.1-4.9 mmol/L High 190 mg/dL and above Above 4.9 mmol/L Very high *Canadian and European guidelines differ slightly from U.S. guidelines.\",\n \"These conversions are based on U.S. guidelines.\",\n \"Elevated LDL cholesterol is, therefore, 160 mg/dL or above (4.1 mmol/L or above).\",\n \"In a Sixteenth Aspect: The ligand of any preceding aspect, wherein the ligand inhibits human PCSK9 binding to human LDL receptor and optionally has been or is determined as capable of such inhibition.\",\n \"In an example, the method comprises (before administering the ligand) determining that the ligand is capable of such inhibition.\",\n \"Inhibition determination is eg, inhibition in a blood or serum sample, at rtp, at ph7, at 37 degrees centigrade and/or under the physiological conditions of a human body.\",\n \"In a Seventeenth Aspect: The ligand of any preceding aspect, wherein the human is resistant or substantially resistant to statin (eg, avorstatin and/or fluvastatin) treatment of said disease or condition.\",\n \"In an Eighteenth Aspect: The ligand of any preceding aspect, wherein the ligand is for treating and/or preventing a PCSK9-mediated disease or condition in a human (i) whose genome comprises SEQ ID NO: 29 and wherein the human is of ASW, YRI, GBR, TSI, CLM, LWK, MXL, JPT, PUR, IBS, FIN or CEU ancestry; or (ii) whose genome comprises SEQ ID NO: 30 and wherein the human is of ASW, YRI, GBR, TSI, CLM, CHB, LWK, CHS, JPT, PUR, FIN or CEU ancestry; or (iii) whose genome comprises SEQ ID NO: 32 and wherein the human is of ASW, GBR, TSI, CLM, JPT, PUR, IBS, FIN or CEU ancestry; or (iv) whose genome comprises SEQ ID NO: 33 and wherein the human is of LWK, ASW, YRI or CLM ancestry; or (v) whose genome comprises SEQ ID NO: 34 and wherein the human is of LWK, ASW or YRI ancestry; or (vi) whose genome comprises SEQ ID NO: 35 and wherein the human is of PUR, TSI, FIN or CEU ancestry; or (vii) whose genome comprises SEQ ID NO: 36 and wherein the human is of LWK, ASW or YRI ancestry; or (viii) whose genome comprises SEQ ID NO: 37 and wherein the human is of CHS, ASW, JPT, PUR or CHB ancestry.\",\n \"In a Ninteenth Aspect: The ligand of any preceding aspect, wherein the ligand is for treating and/or preventing a PCSK9-mediated disease or condition in a human (i) that expresses PCSK9 form f and wherein the human is of ASW, YRI, GBR, TSI, CLM, LWK, MXL, JPT, PUR, IBS, FIN or CEU ancestry; or (ii) that expresses PCSK9 form c and wherein the human is of ASW, YRI, GBR, TSI, CLM, CHB, LWK, CHS, JPT, PUR, FIN or CEU ancestry; or (iii) that expresses PCSK9 form p and wherein the human is of ASW, GBR, TSI, CLM, JPT, PUR, IBS, FIN or CEU ancestry; or (iv) that expresses PCSK9 form m and wherein the human is of LWK, ASW, YRI or CLM ancestry; or (v) that expresses PCSK9 form e and wherein the human is of LWK, ASW or YRI ancestry; or (vi) that expresses PCSK9 form h and wherein the human is of PUR, TSI, FIN or CEU ancestry; or (vii) that expresses PCSK9 form aj and wherein the human is of LWK, ASW or YRI ancestry; or (viii) that expresses PCSK9 form q and wherein the human is of CHS, ASW, JPT, PUR or CHB ancestry.\",\n \"In an example, said forms are the mature forms.\",\n \"In an example, said forms are the pro-forms.\",\n \"In a Twentieth Aspect: A pharmaceutical composition or kit for treating and/or preventing a PCSK9-mediated condition or disease (eg, as recited in aspect 14 or 15), the composition or kit comprising a ligand of any preceding aspect and optionally a statin (eg, cerovastatin, atorvastatin, simvastatin, pitavastin, rosuvastatin, fluvastatin, lovastatin or pravastatin); and optionally in combination with a label or instructions for use to treat and/or prevent said disease or condition in a human (eg, covering treatment of a human as recited in aspect 18 or 19); optionally wherein the label or instructions comprise a marketing authorisation number (eg, an FDA or EMA authorisation number); optionally wherein the label or instructions comprise directions to administer alirocumab or evolocumab to said human; optionally wherein the kit comprises an IV or injection device that comprises the ligand (and, eg, also a statin).\",\n \"In a Twenty-first Aspect: A method of producing an anti-human PCSK9 antibody binding site, the method comprising obtaining a plurality of anti-PCSK9 antibody binding sites, screening the antibody binding sites for binding to a human PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q or a catalytic or C-terminal domain or a peptide thereof that comprises amino acid variation from the corresponding sequence of SEQ ID NO: 1, 2 or 3 and isolating an antibody binding site that binds in the screening step, and optionally producing a form f c, r, p, m, e, h, aj or q PCSK9-binding fragment or derivative of the isolated antibody.\",\n \"In an example, said forms are the mature forms.\",\n \"In an example, said forms are the pro-forms.\",\n \"In an example of this and the next aspect, the plurality of binding sites comprises or consists of a plurality of 4-chain antibodies or fragments thereof, eg, dAbs, Fabs or scFvs.\",\n \"Suitable methods for producing pluralities of binding sites for screening include phage display (producing a phage display library of antibody binding sites), ribosome display (producing a ribosome display library of antibody binding sites), yeast display (producing a yeast display library of antibody binding sites), or immunisation of a non-human vertebrate (eg, a rodent, eg, a mouse or rat, eg, a Velocimouse™, Kymouse™, Xenomouse™, Aliva Mouse™, HuMab Mouse™, Omnimouse™ Omnirat™ or MeMo Mouse™) with a PCSK9 epitope and isolation of a repertoire of antibody-producing cells (eg, a B-cell, plasma cell or plasmablast repertoire) and/or a repertoire of isolated antibodies.\",\n \"In an example, the method comprises selecting one or more antibody binding sites that each specifically binds to a human PCSK9 epitope comprising amino acid variation from the corresponding sequence of SEQ ID NO: 1, 2 or 3.In a Twenty-Second Aspect: A method of producing an anti-human PCSK9 antibody, the method comprising immunising a non-human vertebrate (eg, a mouse or a rat) with a human PCSK9 comprising an amino acid sequence selected from the group consisting of the amino acid sequences of forms f, c, r, p, m, e, h, aj and q or a catalytic or C-terminal domain or a peptide thereof that comprises amino acid variation from the corresponding sequence of SEQ ID NO: 1, 2 or 3 and isolating an antibody that binds a human PCSK9 comprising selected from the group consisting of forms f, c, r, p, m, e, h, aj and q or a catalytic or C-terminal domain or a peptide thereof that comprises amino acid variation from the corresponding sequence of SEQ ID NO: 1, 2 or 3, and optionally producing a form f, c, r, p, m, e, h, aj or q PCSK9-binding fragment or derivative of the isolated antibody.\",\n \"In an example, said forms are the mature forms.\",\n \"In an example, said forms are the pro-forms.\",\n \"In a Twenty-third Aspect: The method of aspect 21 or 22, comprising the step of obtaining a nucleic acid encoding the antibody, fragment, derivative or binding site and optionally inserting the nucleic acid in an expression vector.\",\n \"For example, the method comprises isolating a cell (eg, B-cell, plasmablast, plasma cell or memory cell) comprising the nucleic acid, wherein the cell is obtained from a non-human vertebrate that has been immunised with the PCSK9 epitope.\",\n \"In a Twenty-fourth Aspect: A kit for PCSK9 genotyping a human, wherein the kit comprises a nucleic acid (i) comprising a sequence of 10 or more (eg, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100 or more) contiguous nucleotides that specifically hybridises to a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or at least the catalytic domain- or C-terminal domain-encoding sequence thereof, or specifically hybridises to an antisense sequence or an RNA transcript of said sequence, wherein said sequence of contiguous nucleotides hybridises to at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 or hybridises to an antisense sequence or an RNA transcript thereof, and/or (ii) comprising a sequence of at least 10 or more (eg, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100 or more) nucleotides of a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or comprising an antisense sequence or RNA version of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28.In an example, the nucleotide sequence is selected from the group consisting of SEQ ID NOs: 29-35 and 37; or selected from the group consisting of SEQ ID NOs: 29-32 and 34-37; or selected from the group consisting of SEQ ID NOs: 29-32, 34, 35 and 37.These are naturally-occurring allele (haplotype) sequences that do not encode 46L and which meet the criteria set out above.\",\n \"These groups comprise variants that are associated with elevated LDL-C.\",\n \"In an example, the nucleotide sequence is SEQ ID NO: 34, that encodes a 425S, which is associated with elevated LDL-C (Pisciotta et al 2006).\",\n \"In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31 and 37, that encode 670G which is a marker for severity of coronary atherosclerosis (Chen et al 2005).\",\n \"In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35, 36 and 37; or selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35 and 37.These are allele (haplotype) sequences that have a naturally-occurring combination of differences from SEQ ID NO: 28 (form a) and which meet the criteria set out above.\",\n \"In an example, the nucleotide sequence is SEQ ID NO: 29.In an example, the nucleotide sequence is SEQ ID NO: 30.In an example, the nucleotide sequence is SEQ ID NO: 31.In an example, the nucleotide sequence is SEQ ID NO: 32.In an example, the nucleotide sequence is SEQ ID NO: 33.In an example, the nucleotide sequence is SEQ ID NO: 34.In an example, the nucleotide sequence is SEQ ID NO: 35.In an example, the nucleotide sequence is SEQ ID NO: 36.In an example, the nucleotide sequence is SEQ ID NO: 37.In a Twenty-Fifth Aspect: A kit for PCSK9 genotyping or phenotyping a human, wherein the kit comprises a ligand according to any one of aspects 1 to 19 or an antibody, fragment or derivative produced by the method of any one of aspects 21 to 23.In a Twenty-Sixth Aspect: Use of an anti-PCSK9 ligand that binds a human PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q in the manufacture of a medicament for treating and/or preventing a PCSK9-mediated disease or condition in a human whose genome comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37, optionally for treating and/or preventing a PCSK9-mediated disease or condition in a human as recited in aspect 18 or 19.In an example, said forms are the mature forms.\",\n \"In an example, said forms are the pro-forms.\",\n \"In a Twenty-Seventh Aspect: Use of an anti-PCSK9 ligand that binds a human PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q in the manufacture of a medicament for targeting said PCSK9 in a human to treat and/or prevent a disease or condition mediated by PCSK9, optionally for targeting PCSK9 in a human as recited in aspect 18 or 19.In an example, said forms are the mature forms.\",\n \"In an example, said forms are the pro-forms.\",\n \"In an example, the nucleotide sequence is selected from the group consisting of SEQ ID NOs: 29-35 and 37; or selected from the group consisting of SEQ ID NOs: 29-32 and 34-37; or selected from the group consisting of SEQ ID NOs: 29-32, 34, 35 and 37.These are naturally-occurring allele (haplotype) sequences that do not encode 46L and which meet the criteria set out above.\",\n \"These groups comprise variants that are associated with elevated LDL-C.\",\n \"In an example, the nucleotide sequence is SEQ ID NO: 34, that encodes a 425S, which is associated with elevated LDL-C (Pisciotta et al 2006).\",\n \"In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31 and 37, that encode 670G which is a marker for severity of coronary atherosclerosis (Chen et al 2005).\",\n \"In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35, 36 and 37; or selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35 and 37.These are allele (haplotype) sequences that have a naturally-occurring combination of differences from SEQ ID NO: 28 (form a) and which meet the criteria set out above.\",\n \"In an example, the nucleotide sequence is SEQ ID NO: 29.In an example, the nucleotide sequence is SEQ ID NO: 30.In an example, the nucleotide sequence is SEQ ID NO: 31.In an example, the nucleotide sequence is SEQ ID NO: 32.In an example, the nucleotide sequence is SEQ ID NO: 33.In an example, the nucleotide sequence is SEQ ID NO: 34.In an example, the nucleotide sequence is SEQ ID NO: 35.In an example, the nucleotide sequence is SEQ ID NO: 36.In an example, the nucleotide sequence is SEQ ID NO: 37.The ligand can be any anti-PCSK9 ligand disclosed herein.\",\n \"In a Twenty-Eight Aspect: The use of aspect 26 or 27, wherein the ligand, human, disease or condition is according to any one of aspects 1 to 19.In a Twenty-Ninth Aspect: A method of targeting a PCSK9 for treating and/or preventing a PCSK9-mediated disease or condition in a human, the method comprising administering an anti-PCSK9 ligand to a human comprising a nucleotide sequence selected from the group consisting SEQ ID NOs: 29-37, whereby a PCSK9 encoded by said nucleotide sequence is targeted.\",\n \"The ligand can be any anti-PCSK9 ligand disclosed herein.\",\n \"In a Thirtieth Aspect: The method of aspect 29, wherein the method comprises targeting a human PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q with said ligand to treat and/or prevent said disease or condition in said human.\",\n \"In an example, said forms are the mature forms.\",\n \"In an example, said forms are the pro-forms.\",\n \"In a Thirty-first Aspect: A method of treating and/or preventing a disease or condition mediated by PCSK9 in a human, the method comprising targeting a human PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q by administering to the human a ligand that binds said PCSK9 thereby treating and/or preventing said disease or condition in the human.\",\n \"In an example, said forms are the mature forms.\",\n \"In an example, said forms are the pro-forms.\",\n \"The ligand can be any anti-PCSK9 ligand disclosed herein.\",\n \"In a Thirty-Second Aspect: The method of aspect 31, wherein the genome of the human comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37.In an example, the nucleotide sequence is selected from the group consisting of SEQ ID NOs: 29-35 and 37; or selected from the group consisting of SEQ ID NOs: 29-32 and 34-37; or selected from the group consisting of SEQ ID NOs: 29-32, 34, 35 and 37.These are naturally-occurring allele (haplotype) sequences that do not encode 46L and which meet the criteria set out above.\",\n \"These groups comprise variants that are associated with elevated LDL-C.\",\n \"In an example, the nucleotide sequence is SEQ ID NO: 34, that encodes a 425S, which is associated with elevated LDL-C (Pisciotta et al 2006).\",\n \"In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31 and 37, that encode 670G which is a marker for severity of coronary atherosclerosis (Chen et al 2005).\",\n \"In an example, the nucleotide sequence selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35, 36 and 37; or selected from the group consisting of SEQ ID NOs: 31, 32, 34, 35 and 37.These are allele (haplotype) sequences that have a naturally-occurring combination of differences from SEQ ID NO: 28 (form a) and which meet the criteria set out above.\",\n \"In an example, the nucleotide sequence is SEQ ID NO: 29.In an example, the nucleotide sequence is SEQ ID NO: 30.In an example, the nucleotide sequence is SEQ ID NO: 31.In an example, the nucleotide sequence is SEQ ID NO: 32.In an example, the nucleotide sequence is SEQ ID NO: 33.In an example, the nucleotide sequence is SEQ ID NO: 34.In an example, the nucleotide sequence is SEQ ID NO: 35.In an example, the nucleotide sequence is SEQ ID NO: 36.In an example, the nucleotide sequence is SEQ ID NO: 37.In a Thirty-Third Aspect: The method of any one of aspects 29 to 32, wherein the human has been or is genotyped as positive for a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or the catalytic- or C-terminal domain-encoding sequence thereof.\",\n \"In a Thirty-Fourth Aspect: The method of any one of aspects 29 to 33, wherein the human has been or is phenotyped as positive for a human PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q.\",\n \"In an example, said forms are the mature forms.\",\n \"In an example, said forms are the pro-forms.\",\n \"In a Thirty-Fifth Aspect: The method of any one of aspects 29 to 34, wherein the method comprises genotyping the human as positive for a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or the catalytic- or C-terminal domain-encoding sequence thereof.\",\n \"In a Thirty-Sixth Aspect: The method of any one of aspects 29 to 35, wherein the method comprises phenotyping the human as positive for a human PCSK9 sequence selected from the group consisting of forms f, c, r, p, m, e, h, aj and q.\",\n \"In an example, said forms are the mature forms.\",\n \"In an example, said forms are the pro-forms.\",\n \"In a Thirty-seventh Aspect: The method of any one of aspects 29 to 36, wherein the human has been or is genotyped as heterozygous for a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or the catalytic- or C-terminal domain-encoding sequence thereof, optionally wherein the human has been or is genotyped as comprising the nucleotide sequence of SEQ ID NO: 28 or the catalytic- or C-terminal domain-encoding sequence thereof and a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or the catalytic- or C-terminal domain-encoding sequence thereof.\",\n \"In a Thirty-Eighth Aspect: The method of any one of aspects 29 to 37, wherein the genome of the human has been or is genotyped as homozygous for a nucleotide sequence selected from the group consisting of of SEQ ID NOs: 29-37 or the catalytic- or C-terminal domain-encoding sequence thereof.\",\n \"In a Thirty-Ninth Aspect: The method of any one of aspects 29 to 38, wherein the method comprises genotyping the human for a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or the catalytic- or C-terminal domain-encoding sequence thereof before administering the ligand to the human, wherein the ligand is determined to be capable of binding to a PCSK9 encoded by said selected sequence.\",\n \"In a Fortieth Aspect: The method of any one of aspects 29 to 39, wherein the ligand, human, disease or condition is according to any one of aspects 1 to 19.In a Forty-First Aspect: A method according to any one of aspects 29 to 40 for treating and/or preventing a condition or disease as recited in aspect 14 or 15, the method comprising administering said ligand and a statin (eg, cerovastatin, atorvastatin, simvastatin, pitavastin, rosuvastatin, fluvastatin, lovastatin or pravastatin) to the human.\",\n \"In a Forty-Second Aspect: The method of aspect 41, wherein the ligand and statin are administered separately.\",\n \"In a Forty-Third Aspect: The method of aspect 41, wherein the ligand and statin are administered simultaneously.\",\n \"In a Forty-Fourth Aspect: The method of any one of aspects 29 to 43, wherein the ligand is administered by subcutaneous injection.\",\n \"In a Forty-Fifth Aspect: A method of PCSK9 genotyping a nucleic acid sample of a human, the method comprising identifying in the sample the presence of a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or the catalytic- or C-terminal domain-encoding sequence thereof.\",\n \"In a Forty-Sixth Aspect: A method of PCSK9 typing a protein sample of a human, the method comprising identifying in the sample the presence of a human PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q.\",\n \"In an example, said forms are the mature forms.\",\n \"In an example, said forms are the pro-forms.\",\n \"In a Forty-Seventh Aspect: The method of aspect 45 or 46, comprising obtaining a sample of serum, blood, faeces, hair, tissue, cells, urine or saliva from a human, whereby the nucleic acid or protein sample is obtained and used in the step of identifying said sequence.\",\n \"In a Forty-Eighth Aspect: The method of any one of aspects 45 to 47, comprising using a ligand according to any one of aspects 1 to 19 to carry out said identifying step.\",\n \"In a Forty-Ninth Aspect: A method of treating and/or preventing in a human patient a cardiovascular disease or condition, or a disease or condition that is associated with elevated LDL cholesterol (eg, hypercholesterolaemia), wherein the patient is receiving or has previously received statin treatment for said disease or condition, the method comprising typing the patient using a method of any one of aspects 45 to 48 and administering a ligand according to one of aspects 1 to 19 whereby the human is treated or said disease or condition is prevented; optionally also reducing or stopping statin treatment.\",\n \"In an example, said reducing or stopping comprises reducing the dose and/or dosing frequency of statin.\",\n \"In a Fiftieth Aspect: A diagnostic, therapeutic or prophylactic kit comprising a ligand that is capable of binding to or has been or is determined as capable of binding to an amino acid sequence selected from SEQ ID NOs: 4-27 and instructions for carrying out the method of any one of aspects 46 to 49 and/or a label or instructions indicating or covering administration of the ligand to a human as defined in any one of aspects 1 to 19.In a Fifty-First Aspect: A diagnostic, therapeutic or prophylactic kit comprising a nucleic acid probe comprising a nucleotide sequence that specifically hybridises to a nucleotide sequence selected from the group consisting of SEQ ID NOs: 29-37 or an antisense sequence or RNA transcript thereof and instructions for carrying out the method of aspect 45, 47 or 48.In examples of the present invention, the ligand specifically binds to human PCSK9, eg, one or more of the rare PCSK9 variants disclosed herein (eg, one, two, three, more or all mature forms f, c, r, p, m, e, h, aj and q) and optionally also the a and/or a′ form.\",\n \"For example, the ligand specifically binds to mature form f and/or c as well as form a.\",\n \"Determination of such binding can be performed by any antibody binding test as known in the art, eg, by surface plasmon resonance.\",\n \"Binding to each such form is, for example, respectively with a Kd of at least 1 mM, 100 nM, 1 nM, 100 pM, 10 pM or 1 pM.\",\n \"In an example, the ligand binds form a and a PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q, wherein the ligand binding to said selected form is with a Kd (determined by SPR) that is at least 60, 70, 80, 90 or 95% of the Kd for binding to form a.\",\n \"In an embodiment, both forms are mature forms.\",\n \"In an embodiment, both forms are pro-forms.\",\n \"In an example, the ligand binds form a and form f, wherein the ligand binding to form f is with a Kd (determined by SPR) that is at least 60, 70, 80, 90 or 95% of the Kd for binding to form a.\",\n \"In an embodiment, both forms are mature forms.\",\n \"In an embodiment, both forms are pro-forms.\",\n \"In an example, the ligand binds form a and form c, wherein the ligand binding to form c is with a Kd (determined by SPR) that is at least 60, 70, 80, 90 or 95% of the Kd for binding to form a.\",\n \"In an embodiment, both forms are mature forms.\",\n \"In an embodiment, both forms are pro-forms.\",\n \"In an example, the ligand binds form a and form r, wherein the ligand binding to form r is with a Kd (determined by SPR) that is at least 60, 70, 80, 90 or 95% of the Kd for binding to form a.\",\n \"In an embodiment, both forms are mature forms.\",\n \"In an embodiment, both forms are pro-forms.\",\n \"In an example, the ligand binds form a and form p, wherein the ligand binding to form p is with a Kd (determined by SPR) that is at least 60, 70, 80, 90 or 95% of the Kd for binding to form a.\",\n \"In an embodiment, both forms are mature forms.\",\n \"In an embodiment, both forms are pro-forms.\",\n \"In an example, the ligand binds form a and form m, wherein the ligand binding to form m is with a Kd (determined by SPR) that is at least 60, 70, 80, 90 or 95% of the Kd for binding to form a.\",\n \"In an embodiment, both forms are mature forms.\",\n \"In an embodiment, both forms are pro-forms.\",\n \"In an example, the ligand binds form a and form e, wherein the ligand binding to form e is with a Kd (determined by SPR) that is at least 60, 70, 80, 90 or 95% of the Kd for binding to form a.\",\n \"In an embodiment, both forms are mature forms.\",\n \"In an embodiment, both forms are pro-forms.\",\n \"In an example, the ligand binds form a and form h, wherein the ligand binding to form h is with a Kd (determined by SPR) that is at least 60, 70, 80, 90 or 95% of the Kd for binding to form a.\",\n \"In an embodiment, both forms are mature forms.\",\n \"In an embodiment, both forms are pro-forms.\",\n \"In an example, the ligand binds form a and form aj, wherein the ligand binding to form aj is with a Kd (determined by SPR) that is at least 60, 70, 80, 90 or 95% of the Kd for binding to form a.\",\n \"In an embodiment, both forms are mature forms.\",\n \"In an embodiment, both forms are pro-forms.\",\n \"In an example, the ligand binds form a and form q, wherein the ligand binding to form q is with a Kd (determined by SPR) that is at least 60, 70, 80, 90 or 95% of the Kd for binding to form a.\",\n \"In an embodiment, both forms are mature forms.\",\n \"In an embodiment, both forms are pro-forms.\",\n \"In examples of the present invention, the ligand neutralises human PCSK9, eg, one or more of the rare PCSK9 variants disclosed herein (eg, one, two, three, more or all mature forms f, c, r, p, m, e, h, aj and q) and optionally also the a and/or a′ form.\",\n \"For example, the ligand neutralises mature form f and/or c as well as form a.\",\n \"Determination of neutralisation can be performed, for example, by any neutralisation assay method disclosed in US20120093818A1 (Amgen, Inc) or US20110065902A1 (Regeneron Pharmaceuticals, Inc).\",\n \"Ligands of the invention that bind or target PCSK9 are useful, for example, for therapeutic and prophylactic applications disclosed in US20120093818A1 and US20110065902A1, these specific disclosures being incorporated herein by reference for use in the present invention and for possible inclusion in claims herein.\",\n \"In embodiments where the ligand is used for therapeutic applications, an antigen binding protein can inhibit, interfere with or modulate one or more biological activities of a PCSK9 (eg, one or more of the rare variants disclosed herein and optionally also the a and/or a′ form).\",\n \"In one embodiment, ligand binds specifically to human PCSK9 (eg, one or more of the rare variants disclosed herein and optionally also the a and/or a′ form) and/or substantially inhibits binding of human PCSK9 (eg, said one or more of the rare variants disclosed herein and optionally also the a and/or a′ form) to LDLR by at least 20%, eg, 20%-40%, 40-60%, 60-80%, 80-85%, or more (for example, by measuring binding in an in vitro competitive binding assay).\",\n \"In an example, the ligand is an antibody.\",\n \"In an embodiment, the ligand has a Kd of less (binding more tightly) than 10−7, 10−8, 10−9, 10−10, 10−11, 10−12, 10−13 M for binding to one, two or more of the rare variants disclosed herein and optionally also the a and/or a′ form.\",\n \"In an example, Kd is determined using SPR.\",\n \"In an embodiment, the ligand has an IC50 for blocking the binding of LDLR to one or more of the rare PCSK9 variants disclosed herein (and optionally also the a and/or a′ form) of less than 1 microM, 1000 nM to 100 nM, 100 nM to 10 nM, 10 nM to 1 nM, 1000 pM to 500 pM, 500 pM to 200 pM, less than 200 pM, 200 pM to 150 pM, 200 pM to 100 pM, 100 pM to 10 pM, 10 pM to 1 pM.\",\n \"In an embodiment, the ligand has an IC50 for blocking the binding of LDLR to the a and/or a′ form of PCSK9 that is no more than 1000, 100, 90, 80, 70, 60, 50, 40, 30, 20 or 10-fold more (ie, more inhibitory) than the IC50 for blocking the binding of LDLR to one or more of the rare PCSK9 variants disclosed herein (eg, one or more PCSK9 proteins comprising a sequence selected from SEQ ID NOs: 4 to 27).\",\n \"Additionally or alternatively, for example, the ligand has an IC50 for blocking the binding of LDLR to (i) the a and/or a′ form of less than 1 microM, 1000 nM to 100 nM, 100 nM to 10 nM, 10 nM to 1 nM, 1000 pM to 500 pM, 500 pM to 200 pM, less than 200 pM, 200 pM to 150 pM, 200 pM to 100 pM, 100 pM to 10 pM, 10 pM to 1 pM, eg, in the range of 1 mM to 1 pM (eg, 1 mM to 100 pM; 10 nM to 100 pM; 1 nM to 10 pM; or 100 pM to 1 pM) and (ii) one or more PCSK9 proteins comprising a sequence selected from SEQ ID NOs: 4 to 27 of less than 1 microM, 1000 nM to 100 nM, 100 nM to 10 nM, 10 nM to 1 nM, 1000 pM to 500 pM, 500 pM to 200 pM, less than 200 pM, 200 pM to 150 pM, 200 pM to 100 pM, 100 pM to 10 pM, 10 pM to 1 pM, eg, in the range of 1 mM to 1 pM (eg, 1 mM to 100 pM; 10 nM to 100 pM; 1 nM to 10 pM; or 100 pM to 1 pM).\",\n \"In an embodiment, the ligand binds to the a and/or a′ form of PCSK9 with a binding affinity (Kd) that is greater than up to 10%, greater than up to 20%, greater than up to 40%, greater than up to 50%, greater than up to 55%, greater than up to 60%, greater than up to 65%, greater than up to 70%, greater than up to 75%, greater than up to 80%, greater than up to 85%, greater than up to 90%, greater than up to 95% or greater than up to 100% (ie, is double) relative to binding to a PCSK9 comprising a sequence selected from SEQ ID NOs: 4 to 27.Such binding measurements can be made using a variety of binding assays known in the art, eg, using surface plasmon resonance (SPR), such as by Biacore™ or using the ProteOn XPR36™ (Bio-Rad®), or using KinExA® (Sapidyne Instruments, Inc).\",\n \"In one embodiment, the surface plasmon resonance (SPR) is carried out at 25° C. In another embodiment, the SPR is carried out at 37° C. In one embodiment, the SPR is carried out at physiological pH, such as about pH7 or at pH7.6 (eg, using Hepes buffered saline at pH7.6 (also referred to as HBS-EP)).\",\n \"In one embodiment, the SPR is carried out at a physiological salt level, eg, 150 mM NaCl.\",\n \"In one embodiment, the SPR is carried out at a detergent level of no greater than 0.05% by volume, eg, in the presence of P20 (polysorbate 20; eg, Tween-20™) at 0.05% and EDTA at 3 mM.\",\n \"In one example, the SPR is carried out at 25° C. or 37° C. in a buffer at pH7.6, 150 mM NaCl, 0.05% detergent (eg, P20) and 3 mM EDTA.\",\n \"The buffer can contain 10 mM Hepes.\",\n \"In one example, the SPR is carried out at 25° C. or 37° C. in HBS-EP.\",\n \"HBS-EP is available from Teknova Inc (California; catalogue number H8022).\",\n \"In an example, the affinity of the ligand which is an antibody is determined using SPR by 1.Coupling anti-mouse (or other relevant vertebrate) IgG (eg, Biacore BR-1008-38) to a biosensor chip (eg, GLM chip) such as by primary amine coupling; 2.Exposing the anti-mouse IgG (vertebrate antibody) to a test IgG antibody to capture test antibody on the chip; 3.Passing the test antigen over the chip's capture surface at 1024 nM, 256 nM, 64 nM, 16 nM, 4 nM with a 0 nM (i.e.\",\n \"buffer alone); and 4.And determining the affinity of binding of test antibody to test antigen using surface plasmon resonance, eg, under an SPR condition discussed above (eg, at 25° C. in physiological buffer).\",\n \"SPR can be carried out using any standard SPR apparatus, such as by Biacore™ or using the ProteOn XPR36™ (Bio-Rad®).\",\n \"Regeneration of the capture surface can be carried out with 10 mM glycine at pH1.7.This removes the captured antibody and allows the surface to be used for another interaction.\",\n \"The binding data can be fitted to 1:1 model inherent using standard techniques, eg, using a model inherent to the ProteOn XPR36™ analysis software.\",\n \"In an embodiment, assaying or testing of a ligand of the invention is carried out at or substantially at pH7 (eg, for in vitro tests and assays) and at or substantially at rtp.\",\n \"One example of an IgG2 heavy chain constant domain of an anti-PCSK9 antibody of the present invention has the amino acid sequence as shown in SEQ ID NO: 154, FIG.\",\n \"3KK of US20120093818A1, which sequence is incorporated herein by reference.\",\n \"One example of an IgG4 heavy chain constant domain of an anti-PCSK9 antibody of the present invention has the amino acid sequence as shown in SEQ ID NO: 155, FIG.\",\n \"3KK of US20120093818A1, which sequence is incorporated herein by reference.\",\n \"One example of a kappa light chain constant domain of an anti-PCSK9 antibody has the amino acid sequence as shown in SEQ ID NO: 157, FIG.\",\n \"3KK which sequence is incorporated herein by reference.\",\n \"One example of a lambda light chain constant domain of an anti-PCSK9 antibody has the amino acid sequence as shown in SEQ ID NO: 156, FIG.\",\n \"3KK of US20120093818A1, which sequence is incorporated herein by reference.\",\n \"In examples of the present invention, the ligand binds mature PCSK9, eg, a mature form of one or more of the rare variants disclosed herein and optionally also the a and/or a′ form.\",\n \"In examples of the present invention, the ligand binds the catalytic domain of PCSK9, eg, of a mature form of one or more of the rare variants disclosed herein and optionally also the a and/or a′ form.\",\n \"In examples of the present invention, the ligand binds the prodomain of PCSK9, eg, of a mature form of one or more of the rare variants disclosed herein and optionally also the a and/or a′ form.\",\n \"In some embodiments, the ligand binds to the V domain of PCSK9, eg, of a mature form of one or more of the rare variants disclosed herein and optionally also the a and/or a′ form.\",\n \"In some embodiments, the ligand binds to the V domain of PCSK9 (eg, of a mature form of one or more of the rare variants disclosed herein and optionally also the a and/or a′ form) and prevents (or reduces, eg, by at least 10%) PCSK9 from binding to LDLR.\",\n \"In some embodiments, the ligand binds to the V domain of PCSK9 (eg, of a mature form of one or more of the rare variants disclosed herein and optionally also the a and/or a′ form), and while it does not prevent (or reduce) the binding of PCSK9 to LDLR, the ligand prevents or reduces (eg, by at least 10%) the adverse activities mediated through PCSK9 on LDLR.\",\n \"In examples of the present invention, the ligand is or comprises a fully human antibody.\",\n \"In an example, the ligand comprises human variable regions or humanised variable regions.\",\n \"In an example, the ligand of the invention specifically binds to an epitope of a human PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"For example, the amino acid is selected from the group consisting of 46L, 53V, 425S, 443T, 474V, 619P and 670G (numbering as used in SEQ ID NO: 1).\",\n \"For example, the amino acid is selected from the group consisting of 425S, 443T, 474V, 619P and 670G (numbering as used in SEQ ID NO: 1).\",\n \"For example, the amino acid is selected from the group consisting of 425S and 443T (numbering as used in SEQ ID NO: 1).\",\n \"For example, the amino acid is selected from the group consisting of 474V, 619P and 670G (numbering as used in SEQ ID NO: 1).\",\n \"In an example, the PCSK9 form is the mature form.\",\n \"In an example, the PCSK9 form is the pro-form.\",\n \"In an example, the ligand also specifically binds to form a and/or a′.\",\n \"In an embodiment, the ligand specifically binds to an epitope of form f PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to an epitope of form c PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to an epitope of form r PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to an epitope of form p PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to an epitope of form m PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to an epitope of form e PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to an epitope of form h PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to an epitope of form aj PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to an epitope of form q PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, ligand binds specifically to the pro-domain of a human PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q.\",\n \"In an example, the ligand also specifically binds to the pro-domain of form a and/or a′.\",\n \"In an embodiment, the ligand specifically binds to the pro-domain of form f PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the pro-domain of form c PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the pro-domain of form r PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the pro-domain of form p PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the pro-domain of form m PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the pro-domain of form e PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the pro-domain of form h PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the pro-domain of form aj PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the pro-domain of form q PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, ligand binds specifically to the catalytic domain of a human PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q.\",\n \"In an example, the ligand also specifically binds to the catalytic domain of form a and/or a′.\",\n \"In an embodiment, the ligand specifically binds to the catalytic domain of form f PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the catalytic domain of form c PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the catalytic domain of form r PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the catalytic domain of form p PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the catalytic domain of form m PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the catalytic domain of form e PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the catalytic domain of form h PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the catalytic domain of form aj PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the catalytic domain of form q PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, ligand binds specifically to the C-terminal domain of a human PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q.\",\n \"In an example, the ligand also specifically binds to the C-terminal domain of form a and/or a′.\",\n \"In an embodiment, the ligand specifically binds to the C-terminal domain of form f PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the C-terminal domain of form c PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the C-terminal domain of form r PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the C-terminal domain of form p PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the C-terminal domain of form m PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the C-terminal domain of form e PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the C-terminal domain of form h PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the C-terminal domain of form aj PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the C-terminal domain of form q PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, ligand binds specifically to the substrate-binding groove of a human PCSK9 selected from the group consisting of forms f, c, r, p, m, e, h, aj and q (see Cunningham et al., Nat Struct Mol Biol.\",\n \"2007 May; 14(5):413-9.Epub 2007 Apr.\",\n \"15, “Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia”, incorporated herein in its entirety by reference).\",\n \"In an example, the ligand also specifically binds to the substrate-binding groove of form a and/or a′.\",\n \"In an embodiment, the ligand specifically binds to the Substrate-binding groove of form f PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the Substrate-binding groove of form c PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the Substrate-binding groove of form r PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the Substrate-binding groove of form p PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the Substrate-binding groove of form m PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the Substrate-binding groove of form e PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the Substrate-binding groove of form h PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the Substrate-binding groove of form aj PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"In an embodiment, the ligand specifically binds to the Substrate-binding groove of form q PCSK9, wherein the epitope comprises at least one amino acid that is not found in form a.\",\n \"Reference is made to US20120093818A1 (Amgen, Inc), the entire disclosure of which is incorporated herein.\",\n \"This patent application discloses relevant ligands for use in the present invention, as well as examples and methods of producing and testing ligands that can be used with reference to the present invention.\",\n \"In an example, the ligand is or comprises an antibody disclosed in Table 2 of US20120093818A1 (Amgen, Inc) or is a PCSK9-binding derivative thereof.\",\n \"In an embodiment, the PCSK9-binding ligand of the invention is selected from the antigen binding proteins disclosed in US20120093818A1 (Amgen, Inc), eg, in paragraphs [0009] to [0014] and [0058] to [0063] of US20120093818A1; all of these disclosures (including the sequences of such proteins) are incorporated herein by reference as though explicitly recited herein and for possible inclusion in one or more claims or for use in the present invention.\",\n \"In this paragraph SEQ ID NOs are those as appearing in US20120093818A1 (Amgen, Inc) and these sequences are incorporated herein by reference as though explicitly recited herein and for possible inclusion in one or more claims or for use in the present invention.\",\n \"In some aspects, the ligand of the invention comprises an isolated antigen binding protein that binds PCSK9 comprising: A) one or more heavy chain complementary determining regions (CDRHs) selected from the group consisting of: (i) a CDRH1 from a CDRH1 in a sequence selected from the group consisting of SEQ ID NO: 74, 85, 71, 72, 67, 87, 58, 52, 51, 53, 48, 54, 55, 56, 49, 57, 50, 91, 64, 62, 89, 65, 79, 80, 76, 77, 78, 83, 69, 81, and 60; (ii) a CDRH2 from a CDRH2 in a sequence selected from the group consisting of SEQ ID NO: 74, 85, 71, 72, 67, 87, 58, 52, 51, 53, 48, 54, 55, 56, 49, 57, 50, 91, 64, 62, 89, 65, 79, 80, 76, 77, 78, 83, 69, 81, and 60; (iii) a CDRH3 from a CDRH3 in a sequence selected from the group consisting of SEQ ID NO: 74, 85, 71, 72, 67, 87, 58, 52, 51, 53, 48, 54, 55, 56, 49, 57, 50, 91, 64, 62, 89, 65, 79, 80, 76, 77, 78, 83, 69, 81, and 60; and (iv) a CDRH of (i), (ii), and (iii) that contains one or more amino acid substitutions, deletions or insertions of no more than 4 amino acids; B) one or more light chain complementary determining regions (CDRLs) selected from the group consisting of: (i) a CDRL1 from a CDRL1 in a sequence selected from the group consisting of SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, and 46; (ii) a CDRL2 from a CDRL2 in a sequence selected from the group consisting of SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, and 46; (iii) a CDRL3 from a CDRL3 in a sequence selected from the group consisting of SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, and 46; and (iv) a CDRL of (i), (ii) and (iii) that contains one or more amino acid substitutions, deletions or insertions of no more than 4 amino acids; or C) one or more heavy chain CDRHs of A) and one or more light chain CDRLs of B).\",\n \"In some embodiments, the isolated antigen binding protein comprises at least one CDRH of A) and at least one CDRL of B).\",\n \"In some embodiments, the isolated antigen binding protein comprises at least two CDRH of A) and at least two CDRL of B).\",\n \"In some embodiments, the isolated antigen binding protein comprises said CDRH1, CDRH2, CDRH3, CDRL1, CDRL2 and CDRL3.In some embodiments, the CDRH of A) is selected from at least one of the group consisting of: (i) a CDRH1 amino acid sequence selected from the CDRH1 in a sequence selected from the group consisting of SEQ ID NO: 67, 79, 89, and 49; (ii) a CDRH2 amino acid sequence selected from the CDRH2 in a sequence selected from the group consisting of SEQ ID NO: 67, 79, 89, and 49; (iii) a CDRH3 amino acid sequence selected from the CDRH3 in a sequence selected from the group consisting of SEQ ID NO: 67, 79, 89, and 49; and (iv) a CDRH of (i), (ii) and (iii) that contains one or more amino acid substitutions, deletions or insertions of no more than 2 amino acids.\",\n \"In addition, the CDRL of B) is selected from at least one of the group consisting of: (i) a CDRL1 amino acid sequence selected from the CDRL1 in a sequence selected from the group consisting of SEQ ID NO: 12, 35, 32, and 23; (ii) a CDRL2 amino acid sequence selected from the CDRL2 in a sequence selected from the group consisting of SEQ ID NO: 12, 35, 32, and 23; (iii) a CDRL3 amino acid sequence selected from the CDRL3 in a sequence selected from the group consisting of SEQ ID NO: 12, 35, 32, and 23; and (iv) a CDRL of (i), (ii) and (iii) that contains one or more amino acid substitutions, deletions or insertions of no more than 2 amino acids; or C) one or more heavy chain CDRHs of A) and one or more light chain CDRLs of B.\",\n \"In some embodiments, the CDRH of A) is selected from at least one of the group consisting of: (i) a CDRH1 amino acid sequence of the CDRH1 amino acid sequence in SEQ ID NO: 67; (ii) a CDRH2 amino acid sequence of the CDRH2 amino acid sequence in SEQ ID NO: 67; (iii) a CDRH3 amino acid sequence of the CDRH3 amino acid sequence in SEQ ID NO: 67; and (iv) a CDRH of (i), (ii) and (iii) that contains one or more amino acid substitutions, deletions or insertions of no more than 2 amino acids; said CDRL of B) is selected from at least one of the group consisting of: (i) a CDRL1 amino acid sequence of the CDRL1 amino acid sequence in SEQ ID NO: 12; (ii) a CDRL2 amino acid sequence of the CDRL2 amino acid sequence in SEQ ID NO: 12; (iii) a CDRL3 amino acid sequence of the CDRL3 amino acid sequence in SEQ ID NO: 12; and (iv) a CDRL of (i), (ii) and (iii) that contains one or more amino acid substitutions, deletions or insertions of no more than 2 amino acids; or C) one or more heavy chain CDRHs of A) and one or more light chain CDRLs of B).\",\n \"In some embodiments, the antigen binding protein comprises A) a CDRH1 of the CDRH1 sequence in SEQ ID NO: 67, a CDRH2 of the CDRH2 sequence in SEQ ID NO: 67, and a CDRH3 of the CDRH3 sequence in SEQ ID NO: 67, and B) a CDRL1 of the CDRL1 sequence in SEQ ID NO: 12, a CDRL2 of the CDRL2 sequence in SEQ ID NO: 12, and a CDRL3 of the CDRL3 sequence in SEQ ID NO: 12.In some embodiments, the antigen binding protein comprises a heavy chain variable region (VH) having at least 80% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NO: 74, 85, 71, 72, 67, 87, 58, 52, 51, 53, 48, 54, 55, 56, 49, 57, 50, 91, 64, 62, 89, 65, 79, 80, 76, 77, 78, 83, 69, 81, and 60, and/or a light chain variable region (VL) having at least 80% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, and 46.In some embodiments, the VH has at least 90% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NO: 74, 85, 71, 72, 67, 87, 58, 52, 51, 53, 48, 54, 55, 56, 49, 57, 50, 91, 64, 62, 89, 65, 79, 80, 76, 77, 78, 83, 69, 81, and 60, and/or the VL has at least 90% sequence identity with an amino acid sequence selected from the group consisting of SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, and 46.In some embodiments, the VH is selected from the group consisting of SEQ ID NO: 74, 85, 71, 72, 67, 87, 58, 52, 51, 53, 48, 54, 55, 56, 49, 57, 50, 91, 64, 62, 89, 65, 79, 80, 76, 77, 78, 83, 69, 81, and 60, and/or the VL is selected from the group consisting of SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, and 46.In an example of any aspect of the invention, the PCSK9-targeting or binding ligand comprises or consists of AMG145 or 31H4, 16F12, 11F1, 8A3 or 21B12 disclosed in US20120093818A1 (Amgen, Inc) or an antibody comprising the variable domains of AMG145, 31H4, 16F12, 11F1, 8A3 or 21B12, the disclosures of which (including sequences) are incorporated herein by reference as though explicitly recited herein and for possible inclusion in one or more claims or for use in the present invention.\",\n \"Preferably, the PCSK9-targeting or binding ligand comprises or consists of AMG145.In an example, the AMG145 or other ligand of the invention is glycosylated, eg, has human glycosylation (eg, produced by a CHO, Cos or Hek293 cell).\",\n \"In an example, the ligand of the invention is produced in CHO.\",\n \"Reference is made to US20110065902A1 (Regeneron Pharmaceuticals, Inc), the entire disclosure of which is incorporated herein.\",\n \"This patent application discloses relevant ligands for use in the present invention, as well as examples and methods of producing and testing ligands and determining medical efficacy that can be used with reference to the present invention.\",\n \"Reference is made to the following PCT applications, the entire disclosures of which are incorporated herein.\",\n \"These disclose relevant ligands for use in the present invention, as well as examples and methods of producing and testing ligands and determining medical efficacy that can be used with reference to the present invention.\",\n \"WO2008057457 WO2008057458 WO2008057459 WO2008063382 WO2008133647 WO2009100297 WO2009100318 WO2011037791 WO2011053759 WO2011053783 WO2008125623 WO2011072263 WO2009055783 WO2010029513 WO2011111007 WO2010077854 Antibody ligands to PCSK9 are described in, for example, WO 2008/057457, WO 2008/057458, WO 2008/057459, WO 2008/063382, WO 2008/125623, and US 2008/0008697; each of which is incorporated by reference herein in its entirety.\",\n \"In an example, the ligand is or comprises an antibody disclosed in the Examples of US20110065902A1 (eg, 316P or 300N) or is a PCSK9-binding derivative thereof.\",\n \"All of these disclosures (including the sequences of such proteins and corresponding nucleotide sequences) are incorporated herein by reference as though explicitly recited herein and for possible inclusion in one or more claims or for use in the present invention.\",\n \"In an embodiment, the ligand is or comprises the variable domains of antibody 316P or 300N disclosed in US20110065902A1 or is (or comprises) such antibody or a PCSK9-binding derivative thereof.\",\n \"In an embodiment, the ligand is or comprises the variable domains of antibody alirocumab or SAR236553/REGN727 (Sanofi Aventis/Regeneron) or is (or comprises) such antibody or a PCSK9-binding derivative thereof.\",\n \"In an example, the alirocumab is glycosylated, eg, has human glycosylation (eg, produced by a CHO, Cos or Hek293 cell).\",\n \"Preferably, the ligand is alirocumab or SAR236553/REGN727.In an embodiment, the ligand is or comprises the variable domains of antibody evolocumab or or is (or comprises) such antibody or a PCSK9-binding derivative thereof.\",\n \"In an example, the antibody is glycosylated, eg, has human glycosylation (eg, produced by a CHO, Cos or Hek293 cell).\",\n \"Preferably, the ligand is evolocumab.\",\n \"In an embodiment, the ligand is selected from evolocumab, 1D05-IgG2 (Merck & Co.), ALN-PCS02 (Alnylam), RN316 (Pfizer-Rinat) and alirocumab.\",\n \"In an embodiment, the ligand is selected from the following (sequences and definitions as per US2011/0065902, incorporated herein by reference):— 1.An antibody or antigen-binding fragment thereof which specifically binds hPCSK9, wherein the antibody or antigen-binding fragment comprises the heavy and light chain CDRs of a HCVR/LCVR amino acid sequence pair having SEQ ID NOs: 218/226.2.The antibody or antigen-binding fragment of concept 1 comprising heavy and light chain CDR amino acid sequences having SEQ ID NOs: 220, 222, 224, 228, 230 and 232.3.The antibody or antigen-binding fragment of concept 2 comprising an HCVR having the amino acid sequence of SEQ ID NO: 218 and an LCVR having the amino acid sequence of SEQ ID NO: 226.4.An antibody or antigen-binding fragment thereof which binds to the same epitope on hPCSK9 as an antibody comprising heavy and light chain CDR amino acid sequences having SEQ ID NOs: 220, 222, 224, 228, 230 and 232.5.An antibody or antigen-binding fragment thereof which competes for binding to hPCSK9 with an antibody comprising heavy and light chain CDR amino acid sequences having SEQ ID NOs: 220, 222, 224, 228, 230 and 232.In an embodiment, the ligand is selected from the following (sequences and definitions as per US2012/0093818, incorporated herein by reference):— 1.An isolated neutralizing antigen binding protein that binds to a PCSK9 protein comprising the amino acid sequence of SEQ ID NO: 1, wherein the neutralizing antigen binding protein decreases the LDLR lowering effect of PCSK9 on LDLR, wherein the antigen binding protein comprises a light chain comprising an amino acid sequence of SEQ ID NO: 46, and wherein the antigen binding protein comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 60.2.The isolated neutralizing antigen binding protein of concept 2, wherein the antigen binding protein is a LDLR non-competitive neutralizing antigen binding protein.\",\n \"3.The isolated neutralizing antigen binding protein of concept 2, wherein the antigen binding protein is a LDLR competitive neutralizing antigen binding protein.\",\n \"4.An antigen binding protein that selectively binds to PCSK9, wherein said antigen binding protein binds to PCSK9 with a Kd that is less than 100 pM.\",\n \"5.An antigen binding protein that binds to a PCSK9 protein of SEQ ID NO: 303 in a first manner, wherein the antigen binding protein binds to a variant of PCSK9 in a second manner, wherein said PCSK9 variant has at least one point mutation at a position selected from the group consisting of: 207, 208, 185, 181, 439, 513, 538, 539, 132, 351, 390, 413, 582, 162, 164, 167, 123, 129, 311, 313, 337, 519, 521, and 554 of SEQ ID NO: 303, wherein the first manner comprises a first EC50, a first Bmax, or a first EC50 and a first Bmax, wherein the second manner comprises a second EC50, a second Bmax, or a second EC50 and a second Bmax, and wherein a value for the first manner is different from a value for the second manner, and wherein the antigen binding protein comprises a light chain comprising an amino acid sequence of SEQ ID NO: 46, and wherein the antigen binding protein comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 60.6.The antigen binding protein of concept 6, wherein the first manner comprises a first Bmax, wherein the second manner comprises a second Bmax that is different from the first Bmax, and wherein said PCSK9 variant has at least one point mutation selected from the group consisting of: D162R, R164E, E167R, S123R, E129R, A311R, D313R, D337R, R519E, H521R, and Q554R.\",\n \"7.The antigen binding protein of concept 6, wherein the antigen binding protein binds to PCSK9 at a location that overlaps with a location that LDLR binds to PCSK9.8.A method of making an antigen binding protein that binds to a PCSK9 protein comprising the amino acid sequence of SEQ ID NO: 1, wherein the antigen binding protein decreases the LDLR lowering effect of PCSK9 on LDLR, said method comprising: providing a host cell comprising a nucleic acid sequence that encodes the antigen binding protein; and maintaining the host cell under conditions in which the antigen binding protein is expressed, wherein the antigen binding protein comprises a light chain comprising an amino acid sequence of SEQ ID NO: 46, and wherein the antigen binding protein comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 60.9.A method for treating or preventing a condition associated with elevated serum cholesterol levels in a subject, said method comprising administering to a subject in need thereof an effective amount of an isolated neutralizing antigen binding protein simultaneously or sequentially with an agent that elevates the availability of LDLR protein, wherein the isolated antigen binding protein binds to a PCSK9 protein comprising the amino acid sequence of SEQ ID NO: 1, wherein the neutralizing antigen binding protein decreases the LDLR lowering effect of PCSK9 on LDLR, wherein the antigen binding protein comprises a light chain comprising an amino acid sequence of SEQ ID NO: 46, and wherein the antigen binding protein comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 60.10.The method of concept 10, wherein the agent that elevates the availability of LDLR protein comprises a statin.\",\n \"11.An antigen binding protein that binds to PCSK9, wherein when the antigen binding protein is bound to PCSK9, the antibody is positioned 8 angstroms or less from at least one of the following residues of PCSK9: S153, S188, I189, Q190, S191, D192, R194, E197, G198, R199, V200, D224, R237, D238, K243, S373, D374, S376, T377, F379, I154, T187, H193, E195, I196, M201, V202, C223, T228, S235, G236, A239, G244, M247, 1369, S372, C375, or C378, wherein the antigen binding protein comprises a light chain comprising an amino acid sequence of SEQ ID NO: 46, and wherein the antigen binding protein comprises a heavy chain comprising an amino acid sequence of SEQ ID NO: 60.The ligand can be used for the treatment, therapy, prophylaxis and/or diagnosis of one or more diseases or conditions or susceptibility thereto, wherein such diseases or conditions comprise those disclosed in US20120093818A1 (Amgen, Inc) and US20110065902A1 (Regeneron Pharmaceuticals, Inc), eg, a disease or condition disclosed in paragraphs [0375] to [0383] of US20120093818A1, which disclosure is incorporated herein by reference in its entirety for inclusion in one more claims herein.\",\n \"The ligand can be administered to a human characterised as described in US20120093818A1 (Amgen, Inc) or US20110065902A1.The ligand can be administered in a form or combination disclosed in US20120093818A1 (Amgen, Inc) or US20110065902A1, which disclosure is incorporated herein by reference.\",\n \"For example, the ligand with a drug, excipient, diluent or carrier as described in US20120093818A1 (Amgen, Inc) or US20110065902A1 (eg, as disclose in paragraphs [0384] to [0412] of US20120093818A1), which disclosure is incorporated herein by reference, and the present invention also relates to the corresponding pharmaceutical compositions comprising the combination of a ligand of the invention and such a further agent.\",\n \"The ligand can be used in a method of diagnosis as set out in US20120093818A1 (Amgen, Inc) or US20110065902A1, eg, in paragraphs [0413] to [0415] of US20120093818A1 which disclosure is incorporated herein by reference.\",\n \"Diagnostic Applications In some embodiments, the ligand of the invention is a diagnostic tool.\",\n \"The ligand can be used to assay the amount of PCSK9 present in a sample and/or subject.\",\n \"As will be appreciated by one of skill in the art, such ligands need not be neutralizing ligands.\",\n \"In some embodiments, the diagnostic ligand is not a neutralizing ligand.\",\n \"In some embodiments, the diagnostic ligand binds to a different epitope than a neutralizing ligand binds to.\",\n \"In some embodiments, the two ligands do not compete with one another.\",\n \"In some embodiments, the ligands of the invention are used or provided in an assay kit and/or method for the detection of PCSK9 in mammalian tissues or cells in order to screen/diagnose for a disease or disorder associated with changes in levels of PCSK9.The kit comprises a ligand that binds PCSK9 and means for indicating the binding of the ligand with PCSK9, if present, and optionally PCSK9 protein levels.\",\n \"Various means for indicating the presence of a ligand can be used.\",\n \"For example, fluorophores, other molecular probes, or enzymes can be linked to the ligand and the presence of the ligand can be observed in a variety of ways.\",\n \"The method for screening for such disorders can involve the use of the kit, or simply the use of one of the disclosed ligands and the determination of whether the ligand binds to PCSK9 in a sample.\",\n \"As will be appreciated by one of skill in the art, high or elevated levels of PCSK9 will result in larger amounts of the ligand binding to PCSK9 in the sample.\",\n \"Thus, degree of ligand binding can be used to determine how much PCSK9 is in a sample.\",\n \"Subjects or samples with an amount of PCSK9 that is greater than a predetermined amount (e.g., an amount or range that a person without a PCSK9 related disorder would have) can be characterized as having a PCSK9 mediated disorder.\",\n \"In some embodiments, the invention provides a method wherein the ligand is administered to a subject taking a statin, in order to determine if the statin has increased the amount of PCSK9 in the subject.\",\n \"In some embodiments, the ligand is a non-neutralizing ligand and is used to determine the amount of PCSK9 in a subject receiving an ABP and/or statin treatment.\",\n \"In some embodiments, the ligand of the invention can specifically bind human PCSK9 (eg, one, two or more rare variant forms disclosed herein) and is characterized by at least one of: (i) capable of reducing serum total cholesterol at least about 25-35% and sustaining the reduction over at least a 24 day period relative to a predose level; (ii) capable of reducing serum LDL cholesterol at least about 65-80% and sustaining the reduction over at least a 24 day period relative to a predose level; (iii) capable of reducing serum LDL cholesterol at least about 40-70% and sustaining the reduction over at least a 60 or 90 day period relative to a predose level; (iv) capable of reducing serum triglyceride at least about 25-40% relative to predose level; (v) does not reduce serum HDL cholesterol or reduces serum HDL cholesterol no more than 5% relative to predose level.\",\n \"In some embodiments, an isolated nucleic acid molecule is provided and it encodes the ligand.\",\n \"In some embodiments an expression vector is provided and comprises the nucleic acid molecule.\",\n \"In some embodiments, a pharmaceutical composition is provided and it can comprise the ligand and a pharmaceutically acceptable carrier.\",\n \"In some embodiments, a method is provided for treating a disease or condition which is ameliorated, improved, inhibited or prevented with a PCSK9 antagonist ligand of the invention.\",\n \"The method can comprise administering a therapeutic amount of the pharmaceutical composition or ligand to a subject in need thereof.\",\n \"In some embodiments, the subject is a human subject suffering from hypercholesterolemia, hyperlipidemia, indicated for LDL apheresis, identified as heterozygous for Familial Hypercholesterolemia, statin intolerant.\",\n \"statin uncontrolled, at risk for developing hypercholesterolemia, dyslipidemia, cholestatic liver disease, nephrotic syndrome, hypothyroidism, obesity, atherosclerosis and cardiovascular diseases.\",\n \"In some embodiments, a method of providing a treatment or therapy is provided to a subject.\",\n \"In some embodiments, the method comprises reducing serum cholesterol at least about 40-70% over at least 60 to 90 days.\",\n \"In some embodiments, a method of receiving treatment or therapy is provided, the method can comprise receiving a ligand thereof at a frequency of once every 60 to 90 days.\",\n \"In one aspect, the invention provides a ligand of the invention which is or comprises an human antibody or antigen-binding fragment of a human antibody that specifically binds and inhibits human proprotein convertase subtilisin/kexin type 9 (hPCSK9, eg, one, two or more rare variant forms disclosed herein and optionally form a and/or form a′), characterized by the ability to reduce serum LDL cholesterol in a human by 40-80% over a 24, 60 or 90 day period relative to predose levels, with little or no reduction in serum HDL cholesterol and/or with little or no measurable effect on liver function, as determined by ALT and AST measurements.\",\n \"In one embodiment, the ligand of the invention comprises an antibody or antigen-binding fragment of an antibody that specifically binds hPCSK9 and is characterized by at least one of: (i) capable of reducing serum total cholesterol at least about 25-35% and sustaining the reduction over at least a 24 day period relative to a predose level, preferably the reduction in serum total cholesterol is at least about 30-40%; (ii) capable of reducing serum LDL cholesterol at least about 65-80% and sustaining the reduction over at least a 24 day period relative to a predose level; (iii) capable of reducing serum triglyceride at least about 25-40% relative to predose level; (iv) does not reduce serum HDL cholesterol or reduces serum HDL cholesterol no more than 5% relative to predose level.\",\n \"See US2011/0065902 for definitions of these terms and optional features, the disclosure of which is incorporated herein by reference in its entirety.\",\n \"In one embodiment, the invention comprises an antibody or antigen-binding fragment of an antibody that specifically binds hPCSK9 and is characterized by at least one of: (i) capable of reducing serum LDL cholesterol at least about 40-70% and sustaining the reduction over at least a 60 or 90 day period relative to a predose level; (ii) capable of reducing serum triglyceride at least about 25-40% relative to predose level; (iii) does not reduce serum HDL cholesterol or reduces serum HDL cholesterol no more than 5% relative to predose level.\",\n \"In one embodiment, the antibody or antigen-binding fragment is characterized as exhibiting an enhanced binding affinity (KD) for hPCSK9 at pH 5.5 relative to the KD at pH 7.4, as measured by plasmon surface resonance.\",\n \"In a specific embodiment, the antibody or fragment thereof exhibits at least a 20-fold, at least a 40-fold or at least a 50-fold enhanced affinity for PCSK9 at an acidic pH relative to a neutral pH, as measured by surface plasmon resonance.\",\n \"In one embodiment, the antibody or antigen-binding fragment is characterized as not exhibiting an enhanced binding affinity for PCSK9 at an acidic pH relative to a neutral pH, as measured by surface plasmon resonance.\",\n \"In a specific embodiment, the antibody or fragment thereof exhibits a decreased binding affinity at an acidic pH.\",\n \"In another embodiment, the antibody or antigen-binding fragment binds human, human GOF mutation D374Y, cynomolgus monkey, rhesus monkey, mouse, rat and hamster PCSK9.In one embodiment, the antibody or antigen-binding fragment binds human and monkey PCSK9, but does not bind mouse, rat or hamster PCSK9.In one embodiment, the invention comprises an antibody or antigen-binding fragment of an antibody comprising one or more of a heavy chain variable region (HCVR), light chain variable region (LCVR), HCDR1, HCDR2, HCDR3 disclosed in any of paragraphs [023]-[037] of US2011/0065902, the disclosures of which are incorporated herein by reference.\",\n \"In a related embodiment, the invention comprises an antibody or antigen-binding fragment of an antibody which specifically binds hPCSK9, wherein the antibody or fragment comprises heavy and light chain CDR domains contained within heavy and light chain sequence pairs selected from the group consisting of SEQ ID NO (using the sequence numbering in US2011/0065902): 2/10, 18/20, 22/24, 26/34, 42/44, 46/48, 50/58, 66/68, 70/72, 74/82, 90/92, 94/96, 98/106, 114/116, 118/120, 122/130, 138/140, 142/144, 146/154, 162/164, 166/168, 170/178, 186/188, 190/192, 194/202, 210/212, 214/216, 218/226, 234/236, 238/240, 242/250, 258/260, 262/264, 266/274, 282/284, 286/288, 290/298, 306/308, 310/312, 314/322, 330/332, 334/336, 338/346, 354/356, 358/360, 362/370, 378/380, 382/384, 386/394, 402/404, 406/408, 410/418, 426/428, 430/432, 434/442, 450/452, 454/456, 458/466, 474/476, 478/480, 482/490, 498/500, 502/504, 506/514, 522/524, 526/528, 530/538, 546/548, 550/552, 554/562, 570/572, 574/576, 578/586, 594/596, 598/600, 602/610, 618/620, 622/624, 626/634, 642/644, 646/648, 650/658, 666/668, 670/672, 674/682, 690/692, 694/696, 698/706, 714/716, 718/720, 722/730, 738/740 and 742/744.In one embodiment, the CDR sequences are contained within HCVR and LCVR selected from the amino acid sequence pairs of SEQ ID NO: 50/58, 66/68, 70/72, 74/82, 90/92, 94/96, 122/130, 138/140, 142/144, 218/226, 234/236, 238/240, 242/250, 258/260, 262/264, 314/322, 330/332 and 334/336.In more specific embodiments, the CDR sequences are comprised within HCVR/LCVR sequences selected from SEQ ID NO: 90/92 or 218/226.In an example, the invention features a pharmaceutical composition comprising a ligand of the invention, wherein the ligand comprises or consists of a recombinant human antibody or fragment thereof which specifically binds hPCSK9 and a pharmaceutically acceptable carrier.\",\n \"In one embodiment, the invention features a composition which is a combination of a ligand of the invention (eg, an antibody or antigen-binding fragment of an antibody), and a second therapeutic agent.\",\n \"The second therapeutic agent may be any agent that is advantageously combined with the ligand of the invention, for example, an agent capable of inducing a cellular depletion of cholesterol synthesis by inhibiting 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase, such as, for example, cerovastatin, atorvastatin, simvastatin, pitavastin, rosuvastatin, fluvastatin, lovastatin, pravastatin, etc; capable of inhibiting cholesterol uptake and or bile acid re-absorption; capable of increasing lipoprotein catabolism (such as niacin); and/or activators of the LXR transcription factor that plays a role in cholesterol elimination such as 22-hydroxycholesterol.\",\n \"In an example, the invention provides a method for inhibiting hPCSK9 activity using the anti-PCSK9 ligand of the invention (eg, an antibody or antigen-binding portion of the antibody of the invention), wherein the therapeutic methods comprise administering a therapeutically effective amount of a pharmaceutical composition comprising an antibody or antigen-binding fragment of an antibody of the invention.\",\n \"The disorder treated is any disease or condition which is improved, ameliorated, inhibited or prevented by removal, inhibition or reduction of PCSK9 activity.\",\n \"Specific populations treatable by the therapeutic methods of the invention include subjects indicated for LDL apheresis, subjects with PCSK9-activating mutations (gain of function mutations, “GOF”), subjects with heterozygous Familial Hypercholesterolemia (heFH); subjects with primary hypercholesterolemia who are statin intolerant or statin uncontrolled; and subjects at risk for developing hypercholesterolemia who may be preventably treated.\",\n \"Other indications include dyslipidemia associated with secondary causes such as Type 2 diabetes mellitus, cholestatic liver diseases (primary biliary cirrhosis), nephrotic syndrome, hypothyroidism, obesity; and the prevention and treatment of atherosclerosis and cardiovascular diseases.\",\n \"In specific embodiments of the method of the invention, the ligand of the invention (eg, anti-hPCSK9 antibody or antibody fragment of the invention) is useful to reduce elevated total cholesterol, non-HDL cholesterol, LDL cholesterol, and/or apolipoprotein B (apolipoprotein B100).\",\n \"The ligand (eg, antibody or antigen-binding fragment) of the invention may be used alone or in combination with a second agent, for example, an HMG-CoA reductase inhibitor and/or another lipid lowering drug.\",\n \"Treatment Population The invention provides therapeutic methods for treating a human patient in need of a composition or ligand of the invention.\",\n \"While modifications in lifestyle and conventional drug treatment are often successful in reducing cholesterol levels, not all patients are able to achieve the recommended target cholesterol levels with such approaches.\",\n \"Various conditions, such as familial hypercholesterolemia (FH), appear to be resistant to lowering of LDL-C levels in spite of aggressive use of conventional therapy.\",\n \"Homozygous and heterozygous familial hypercholesterolemia (hoFH, heFH) is a condition associated with premature atherosclerotic vascular disease.\",\n \"However, patients diagnosed with hoFH are largely unresponsive to conventional drug therapy and have limited treatment options.\",\n \"Specifically, treatment with statins, which reduce LDL-C by inhibiting cholesterol synthesis and upregulating the hepatic LDL receptor, may have little effect in patients whose LDL receptors are non-existent or defective.\",\n \"A mean LDL-C reduction of only less than about 20% has been recently reported in patients with genotype-confirmed hoFH treated with the maximal dose of statins.\",\n \"The addition of ezetimibe 10 mg/day to this regimen resulted in a total reduction of LDL-C levels of 27%, which is still far from optimal.\",\n \"Likewise, many patients are statin non-responsive, poorly controlled with statin therapy, or cannot tolerate statin therapy; in general, these patients are unable to achieve cholesterol control with alternative treatments.\",\n \"There is a large unmet medical need for new treatments that can address the short-comings of current treatment options.\",\n \"Specific populations treatable by the therapeutic methods of the invention include patients indicated for LDL apheresis, subjects with PCSK9-activating (GOF) mutations, heterozygous Familial Hypercholesterolemia (heFH); subjects with primary hypercholesterolemia who are statin intolerant or statin uncontrolled; and subjects at risk for developing hypercholesterolemia who may be preventably treated.\",\n \"Therapeutic Administration and Formulations The invention provides therapeutic compositions comprising the anti-PCSK9 ligands, antibodies or antigen-binding fragments thereof of the present invention.\",\n \"The administration of therapeutic compositions in accordance with the invention will be administered with suitable carriers, excipients, and other agents that are incorporated into formulations to provide improved transfer, delivery, tolerance, and the like.\",\n \"A multitude of appropriate formulations can be found in the formulary known to all pharmaceutical chemists: Remington's Pharmaceutical Sciences, Mack Publishing Company, Easton, Pa.\",\n \"These formulations include, for example, powders, pastes, ointments, jellies, waxes, oils, lipids, lipid (cationic or anionic) containing vesicles (such as LIPOFECTINT™), DNA conjugates, anhydrous absorption pastes, oil-in-water and water-in-oil emulsions, emulsions carbowax (polyethylene glycols of various molecular weights), semi-solid gels, and semi-solid mixtures containing carbowax.\",\n \"See also Powell et al.\",\n \"“Compendium of excipients for parenteral formulations” PDA (1998) J Pharm Sci Technol 52:238-311.The dose may vary depending upon the age and the size of a subject to be administered, target disease, conditions, route of administration, and the like.\",\n \"When the ligand, eg, antibody, of the present invention is used for treating various conditions and diseases associated with PCSK9, including hypercholesterolemia, disorders associated with LDL and apolipoprotein B, and lipid metabolism disorders, and the like, in an adult patient, it is advantageous to intravenously administer the ligand or antibody of the present invention normally at a single dose of about 0.01 to about 20 mg/kg body weight, more preferably about 0.02 to about 7, about 0.03 to about 5, or about 0.05 to about 3 mg/kg body weight.\",\n \"Depending on the severity of the condition, the frequency and the duration of the treatment can be adjusted.\",\n \"Various delivery systems are known and can be used to administer the pharmaceutical composition of the invention, thus the composition invention provides the ligand by e.g., encapsulation in liposomes, microparticles, microcapsules, recombinant cells capable of expressing the mutant viruses, receptor mediated endocytosis (see, e.g., Wu et al.\",\n \"(1987) J. Biol.\",\n \"Chem.\",\n \"262:4429-4432).\",\n \"Methods of introduction include, but are not limited to, intradermal, intramuscular, intraperitoneal, intravenous, subcutaneous, intranasal, epidural, and oral routes.\",\n \"The composition may be administered by any convenient route, for example by infusion or bolus injection, by absorption through epithelial or mucocutaneous linings (e.g., oral mucosa, rectal and intestinal mucosa, etc.)\",\n \"and may be administered together with other biologically active agents.\",\n \"Administration can be systemic or local.\",\n \"The pharmaceutical composition can be also delivered in a vesicle, in particular a liposome (see Langer (1990) Science 249:1527-1533; Treat et al.\",\n \"(1989) in Liposomes in the Therapy of Infectious Disease and Cancer, Lopez Berestein and Fidler (eds.\",\n \"), Liss, New York, pp.\",\n \"353-365; Lopez-Berestein, ibid., pp.\",\n \"317-327; see generally ibid.).\",\n \"In certain situations, the pharmaceutical composition can be delivered in a controlled release system.\",\n \"In one embodiment, a pump may be used (see Langer, supra; Sefton (1987) CRC Crit.\",\n \"Ref Biomed.\",\n \"Eng.\",\n \"14:201).\",\n \"In another embodiment, polymeric materials can be used; see, Medical Applications of Controlled Release, Langer and Wise (eds.\",\n \"), CRC Pres., Boca Raton, Fla. (1974).\",\n \"In yet another embodiment, a controlled release system can be placed in proximity of the composition's target, thus requiring only a fraction of the systemic dose (see, e.g., Goodson, in Medical Applications of Controlled Release, supra, vol.\",\n \"2, pp.\",\n \"115-138, 1984).\",\n \"The injectable preparations may include dosage forms for intravenous, subcutaneous, intracutaneous and intramuscular injections, drip infusions, etc.\",\n \"These injectable preparations may be prepared by methods publicly known.\",\n \"For example, the injectable preparations may be prepared, e.g., by dissolving, suspending or emulsifying the antibody or its salt described above in a sterile aqueous medium or an oily medium conventionally used for injections.\",\n \"As the aqueous medium for injections, there are, for example, physiological saline, an isotonic solution containing glucose and other auxiliary agents, etc., which may be used in combination with an appropriate solubilizing agent such as an alcohol (e.g., ethanol), a polyalcohol (e.g., propylene glycol, polyethylene glycol), a nonionic surfactant [e.g., polysorbate 80, HCO-50 (polyoxyethylene (50 mol) adduct of hydrogenated castor oil)], etc.\",\n \"As the oily medium, there are employed, e.g., sesame oil, soybean oil, etc., which may be used in combination with a solubilizing agent such as benzyl benzoate, benzyl alcohol, etc.\",\n \"The injection thus prepared is preferably filled in an appropriate ampoule.\",\n \"A pharmaceutical composition of the present invention can be delivered subcutaneously or intravenously with a standard needle and syringe.\",\n \"In addition, with respect to subcutaneous delivery, a pen delivery device readily has applications in delivering a pharmaceutical composition of the present invention.\",\n \"Such a pen delivery device can be reusable or disposable.\",\n \"A reusable pen delivery device generally utilizes a replaceable cartridge that contains a pharmaceutical composition.\",\n \"Once all of the pharmaceutical composition within the cartridge has been administered and the cartridge is empty, the empty cartridge can readily be discarded and replaced with a new cartridge that contains the pharmaceutical composition.\",\n \"The pen delivery device can then be reused.\",\n \"In a disposable pen delivery device, there is no replaceable cartridge.\",\n \"Rather, the disposable pen delivery device comes prefilled with the pharmaceutical composition held in a reservoir within the device.\",\n \"Once the reservoir is emptied of the pharmaceutical composition, the entire device is discarded.\",\n \"Numerous reusable pen and autoinjector delivery devices have applications in the subcutaneous delivery of a pharmaceutical composition of the present invention.\",\n \"Examples include, but certainly are not limited to AUTOPEN™ (Owen Mumford, Inc., Woodstock, UK), DISETRONIC™ pen (Disetronic Medical Systems, Burghdorf, Switzerland), HUMALOG MIX 75/25™ pen, HUMALOG™ pen, HUMALIN 70/30™ pen (Eli Lilly and Co., Indianapolis, Ind.\",\n \"), NOVOPEN™ I, II and III (Novo Nordisk, Copenhagen, Denmark), NOVOPEN JUNIOR™ (Novo Nordisk, Copenhagen, Denmark), BD™ pen (Becton Dickinson, Franklin Lakes, N.J.), OPTIPENT™, OPTIPEN PRO™, OPTIPEN STARLET™, and OPTICLIKT™ (sanofi-aventis, Frankfurt, Germany), to name only a few.\",\n \"Examples of disposable pen delivery devices having applications in subcutaneous delivery of a pharmaceutical composition of the present invention include, but certainly are not limited to the SOLOSTAR™ pen (sanofi-aventis), the FLEXPEN™ (Novo Nordisk), and the KWIKPEN™ (Eli Lilly).\",\n \"Advantageously, the pharmaceutical compositions for oral or parenteral use described above are prepared into dosage forms in a unit dose suited to fit a dose of the active ingredients.\",\n \"Such dosage forms in a unit dose include, for example, tablets, pills, capsules, injections (ampoules), suppositories, etc.\",\n \"The amount of the aforesaid antibody contained is generally about 5 to about 500 mg per dosage form in a unit dose; especially in the form of injection, it is preferred that the aforesaid antibody is contained in about 5 to about 100 mg and in about 10 to about 250 mg for the other dosage forms.\",\n \"The invention provides therapeutic methods in which the ligand, eg, antibody or antibody fragment, of the invention is useful to treat hypercholesterolemia associated with a variety of conditions involving hPCSK9.The anti-PCSK9 ligands, eg, antibodies or antibody fragments, of the invention are particularly useful for the treatment of hypercholesterolemia and the like.\",\n \"Combination therapies may include the anti-PCSK9 ligand of the invention with, for example, one or more of any agent that (1) induces a cellular depletion of cholesterol synthesis by inhibiting 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase, such as cerivastatin, atorvastatin, simvastatin, pitavastatin, rosuvastatin, fluvastatin, lovastatin, pravastatin; (2) inhibits cholesterol uptake and or bile acid re-absorption; (3) increase lipoprotein catabolism (such as niacin); and activators of the LXR transcription factor that plays a role in cholesterol elimination such as 22-hydroxycholesterol or fixed combinations such as ezetimibe plus simvastatin; a statin with a bile resin (e.g., cholestyramine, colestipol, colesevelam), a fixed combination of niacin plus a statin (e.g., niacin with lovastatin); or with other lipid lowering agents such as omega-3-fatty acid ethyl esters (for example, omacor).\",\n \"Tailoring Antibodies to Rare PCSK9 Variant Profile As outline above, the invention includes the possibility to tailor treatment of humans further by selecting antibody-based ligands with variable domains based on gene segments commonly found in humans of the ethnic populations where the variant PCSK9 forms are found to meet the selection criteria of the invention.\",\n \"An example is provided below for ligands comprising antibody VH domains derived from recombination of human VH3-23.The inventor analysed the frequencies and distribution of various human VH3-23 alleles and realised the desirability of using ligands based on human VH3-23 alleles comprising SNP rs56069819.This SNP corresponds to a change from leucine at position 24 in the encoded protein sequence to a valine at that position (L24V change) and the SNP is at coordinate 106268889 on human chromosome 14.FIG.\",\n \"2 shows the cumulative allele frequency distribution across the 1000 Genomes Project database of human VH3-23 alleles comprising SNP rs56069819 (such alleles denoted “C” and the most frequent allele (which does not comprise this SNP) denoted “A”).\",\n \"The figure shows that VH3-23 alleles comprising SNP rs56069819 are present at a cumulative frequency of 11% across all human ethnic populations taken as a whole, whereas in certain specific human ethnic sub-populations (ASW, LWK, YRI, CEU and GBR) such alleles are present at an above-average cumulative frequency.\",\n \"Indicated in the figure are those human PCSK9 variant forms (marked “Variants”) that are found in the various sub-populations with above-average occurrence of human VH3-23 alleles comprising SNP rs56069819.Table 7 shows the VH3-23 variants and the SNPs that they comprise, as well as their cumulative allele frequencies as found in the 1000 Genomes Project database.\",\n \"Notably, human VH3-23 alleles comprising SNP rs56069819 were found in the CEU population at a frequency that is almost double the frequency of 11% for all populations.\",\n \"For the ASW and YRI populations the frequency was over a quarter of the population.\",\n \"Thus, the invention advantageously enables one to select a ligand comprising an antibody or antibody fragment, wherein the antibody or fragment comprises a VH domain derived from the recombination of a human VH gene segment, a human D gene segment and a human JH gene segment, the VH gene segment comprising a nucleotide sequence that comprises SNP rs56069819 (dbSNP numbering, build number as recited above).\",\n \"In an example, one can tailor the treatment further by selecting such a ligand that specifically binds to a human PCSK9 selected from forms: f, c, m, e, h, p, q and aj, such forms being those appearing in human populations ASW, LWK, YRI, CEU and GBR.\",\n \"In an example, the VH gene segment is VH3-23*04, which is a commonly found variant that comprises SNP rs56069819 in human populations ASW, LWK, YRI, CEU and GBR.\",\n \"In an example, the ligand is for treating and/or preventing a PCSK9-mediated disease or condition in a human that expresses a human PCSK9 selected from forms: f, c, m, e, h, p, q and aj.\",\n \"In an example, the ligand is for treating and/or preventing a PCSK9-mediated disease or condition in a human of ASW, LWK, YRI, CEU or GBR ancestry.\",\n \"In an embodiment, the ligand is for treating and/or preventing a PCSK9-mediated disease or condition in a human of ASW ancestry, wherein the human expresses a PCSK9 selected from f, c, m, e, h, p and q or the human comprises a corresponding nucleotide or amino acid sequence as set out in Table 6.Optionally this ligand comprises a VH domain derived from recombination of human VH3-23*04.In an embodiment, the ligand is for treating and/or preventing a PCSK9-mediated disease or condition in a human of LWK ancestry, wherein the human expresses a PCSK9 selected from f, c, m, e and h or the human comprises a corresponding nucleotide or amino acid sequence as set out in Table 6.Optionally this ligand comprises a VH domain derived from recombination of human VH3-23*04.In an embodiment, the ligand is for treating and/or preventing a PCSK9-mediated disease or condition in a human of YRI ancestry, wherein the human expresses a PCSK9 selected from f, c, m, e and h or the human comprises a corresponding nucleotide or amino acid sequence as set out in Table 6.Optionally this ligand comprises a VH domain derived from recombination of human VH3-23*04.In an embodiment, the ligand is for treating and/or preventing a PCSK9-mediated disease or condition in a human of CEU ancestry, wherein the human expresses a PCSK9 selected from f, c, p and aj or the human comprises a corresponding nucleotide or amino acid sequence as set out in Table 6.Optionally this ligand comprises a VH domain derived from recombination of human VH3-23*04.In an embodiment, the ligand is for treating and/or preventing a PCSK9-mediated disease or condition in a human of GBR ancestry, wherein the human expresses a PCSK9 selected from f c and p or the human comprises a corresponding nucleotide or amino acid sequence as set out in Table 6.Optionally this ligand comprises a VH domain derived from recombination of human VH3-23*04.In an example, the ligand is alirocumab.\",\n \"In other embodiments, as explained more fully above, the invention provides for ligands which are tailored to the human recipient's genotype and/or phenotype based on alternative human VH gene segments, or on Vκ, Vλ or constant region gene segments (see further Table 9 for representative variants).\",\n \"For example, the ligand of the invention comprises or consists of an antibody that comprises a VH domain that is derived from the recombination of a human VH gene segment, a human D gene segment and a human JH gene segment, wherein the VH gene segment is selected from the group consisting of (i) IGHV1-18*01 and the genome of the human comprises a human IGHV1-18*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGHV1-18*01; or (ii) IGVH1-46*01 and the genome of the human comprises a human IGHV1-46*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGHV1-46*01.For example, the ligand of the invention comprises or consists of an antibody that comprises a VL domain that is derived from the recombination of a human VL gene segment and a human JL gene segment, wherein the VL gene segment is selected from the group consisting of (i) IGKV4-1*01 and the genome of the human comprises a human IGKV4-1*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGKV4-1*01; (ii) IGLV2-14*01 and the genome of the human comprises a human IGLV2-14*01 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGLV2-14*01; or (iii) IGKV1-13*02 and the genome of the human comprises a human IGKV1-13*02 nucleotide sequence or the human expresses antibodies comprising variable domains derived from the recombination of human IGKV1-13*02.For example, the inventor identified the possibility of addressing the rarer IGH-gamma-1 SNPs 204D (observed cumulative frequency of 0.296) and 206L (observed cumulative frequency of 0.283) individually or in combination.\",\n \"These residues are part of the CH3 domain, and as such they form part of antibody Fc regions.\",\n \"Thus, matching of these CH3 variations with the patient is especially beneficial for reasons as discussed above.\",\n \"Thus, in this example the ligand of the invention comprises or consists of an antibody that comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 or a Leu corresponding to position 206 of SEQ ID NO: 42 and wherein the genome of the human comprises a gamma-1 heavy chain constant region nucleotide sequence that encodes such an Asp or Leu or the human expresses antibodies comprising human gamma-1 constant regions comprising such an Asp or Leu.\",\n \"An example of such a ligand is alirocumab.\",\n \"In another example, the inventor identified the possibility of addressing IGH-gamma-2 SNPs.\",\n \"This included consideration of Fc region variation—in this respect, the inventor focused on positions 161 and 257 which are in the Fc region.\",\n \"Thus, in this example the ligand of the invention comprises or consists of an antibody that comprises a human gamma-2 heavy chain constant region that comprises an amino acid selected from the group consisting of a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44, a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44; and wherein the genome of the human comprises a gamma-2 heavy chain constant region nucleotide sequence that encodes such a selected amino acid or the human expresses antibodies comprising human gamma-2 constant regions comprising such a selected amino acid.\",\n \"An example of such a ligand is evolocumab or bococizumab.\",\n \"In another example, the inventor addressed human kappa constant region variation.\",\n \"Thus, in this example the ligand of the invention comprises or consists of an antibody that comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 or a Cys corresponding to position 87 of SEQ ID NO: 50; and wherein the genome of the human comprises a kappa light chain constant region nucleotide sequence that encodes such a Val or Cys or the human expresses antibodies comprising human kappa light chain constant regions comprising such a Val or Cys.\",\n \"An example of such a ligand is alirocumab or bococizumab.\",\n \"In another example, the inventor addressed human lambda constant region variation.\",\n \"Thus, in this example the ligand of the invention comprises or consists of an antibody that comprises a human IGLC2*01 light chain constant region; and wherein the genome of the human comprises a human IGLC2*01 nucleotide sequence or the human expresses antibodies comprising human light chain IGLC2*01 constant regions.\",\n \"An example of such a ligand is evolocumab.\",\n \"Further exemplary ligands are in the paragraphs 1-17 as follows.\",\n \"1.An antibody or antibody fragment for use in a method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, wherein the antibody or fragment comprises a human gamma heavy chain constant region that comprises a first amino acid that is encoded by a human gamma heavy chain constant region gene segment SNP, and the antibody or fragment specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) amino acid sequence that comprises a C-terminal domain comprising a mutation I474V or E670G in SEQ ID NO: 1, wherein the human comprises a nucleotide sequence encoding said PCSK9 amino acid sequence and comprises a human gamma heavy chain constant region gene segment comprising said SNP, or the human expresses antibodies comprising human gamma constant regions comprising said first amino acid.\",\n \"In an alternative, paragraph 1 provides:— An antibody or antibody fragment for use in a method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, wherein the antibody or fragment comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 or a Leu corresponding to position 206 of SEQ ID NO: 42, and the antibody or fragment specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) amino acid sequence that comprises a C-terminal domain comprising a mutation I474V or E670G in SEQ ID NO: 1, wherein the human comprises a nucleotide sequence encoding said amino acid sequence and comprises an IGHG1*01 human heavy chain constant region gene segment, or the human expresses antibodies comprising human gamma-1 constant regions comprising such an Asp and Leu.\",\n \"In an embodiment, said mutation is I474V.\",\n \"In another embodiment, said mutation is E670G.\",\n \"An example provides:— An antibody or antibody fragment for use in a method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, wherein the antibody or fragment comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 and a Leu corresponding to position 206 of SEQ ID NO: 42, and the antibody or fragment specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) amino acid sequence that comprises a C-terminal domain comprising a mutation I474V in SEQ ID NO: 1, wherein the human comprises a nucleotide sequence encoding said amino acid sequence and comprises an IGHG1*01 human heavy chain constant region gene segment.\",\n \"Optionally, the antibody or fragment comprises an IGHG1*01 human heavy chain constant region.\",\n \"Another example provides:— An antibody or antibody fragment for use in a method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, wherein the antibody or fragment comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 and a Leu corresponding to position 206 of SEQ ID NO: 42, and the antibody or fragment specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) amino acid sequence that comprises a C-terminal domain comprising a mutation E670G in SEQ ID NO: 1, wherein the human comprises a nucleotide sequence encoding said amino acid sequence and comprises an IGHG1*01 human heavy chain constant region gene segment.\",\n \"Optionally, the antibody or fragment comprises an IGHG1*01 human heavy chain constant region.\",\n \"In an example, said antibody or antibody fragment has been determined to specifically bind a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 or E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 and a Leu corresponding to position 206 of SEQ ID NO: 42 and wherein said human comprises (i) an IGHG1*01 human heavy chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.2.The antibody or antibody fragment of paragraph 1, wherein the antibody comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 and a Leu corresponding to position 206 of SEQ ID NO: 42.3.The antibody or antibody fragment of paragraph 1 or 2, wherein the antibody comprises an IGHG1*01 human heavy chain constant region.\",\n \"4.The antibody or antibody fragment of any one of paragraphs 1 to 3, wherein the human has been determined to comprise the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1 and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein encoded by the nucleotide sequence of SEQ ID NO: 29 or 30.5.The antibody or antibody fragment of any one of paragraphs 1 to 4, the method comprising the step of determining that the human comprises the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein comprising said mutation I474V or E670G, optionally, wherein the determining step is performed before administration of the antibody to the human.\",\n \"6.The antibody or antibody fragment of paragraph 5, wherein the step of determining comprises assaying a biological sample from the human for a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.7.The antibody or antibody fragment of paragraph 6, wherein the assaying comprises contacting the biological sample with a. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides that can specifically hybridize to and identify in the biological sample a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or that specifically hybridizes to an antisense of said sequence, wherein said nucleic acid hybridizes to at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 or hybridizes to an antisense sequence thereby forming a complex when at least one nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and/or b. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides of a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or comprising an antisense sequence of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 thereby forming a complex when the nucleotide sequence encoding the PCSK9 that comprises a C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and detecting the presence or absence of the complex, wherein detecting the presence of the complex determines that the human comprises the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.8.The antibody or antibody fragment of paragraph 6 or 7, wherein the assaying comprises nucleic acid amplification and optionally one or more methods selected from sequencing, next generation sequencing, nucleic acid hybridization, and allele-specific amplification and/or wherein the assaying is performed in a multiplex format.\",\n \"9.The antibody or antibody fragment of any one of paragraphs 1 to 8, wherein said antibody or antibody fragment is for administration to a human that is or has been further determined to be substantially resistant to statin treatment.\",\n \"10.The antibody or antibody fragment of any one of paragraphs 1 to 9, wherein antibody or antibody fragment is for administration to a human that is receiving or has received statin treatment or has reduced responsiveness to statin treatment.\",\n \"11.The antibody or antibody fragment of paragraph 9 or 10, wherein said antibody or antibody fragment is for administration to the human separately or simultaneously with said statin treatment.\",\n \"12.The antibody or antibody fragment of any one of paragraphs 6 to 10, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine and/or saliva of said human.\",\n \"13.The antibody or antibody fragment of any one of paragraphs 1 to 12, wherein said human is indicated as heterozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising a mutation I474V or E670G, optionally, wherein said human is further indicated as comprising the nucleotide sequence of SEQ ID NO: 28, or said human is indicated as homozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising a mutation I474V or E670G in SEQ ID NO: 1.14.The antibody or antibody fragment of any one of paragraphs 1 to 13, wherein said human has been diagnosed with at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.\",\n \"15.The antibody or antibody fragment of any one of paragraphs 1 to 14, wherein said antibody or antibody fragment treats or reduces the risk in said human of at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.\",\n \"16.The antibody or antibody fragment of any one of paragraphs 1 to 15, wherein the nucleotide sequence is SEQ ID NO: 29 or 30.17.The antibody or antibody fragment of any one of paragraphs 1 to 16, wherein said antibody or antibody fragment is for administration by intravenous or subcutaneous administration and/or is comprised in an injectable preparation.\",\n \"Further exemplary methods are in the paragraphs 1-18 as follows.\",\n \"1.A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 or E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 or a Leu corresponding to position 206 of SEQ ID NO: 42 and wherein said human comprises (i) an IGHG1*01 human heavy chain constant region gene segment, or the human expresses antibodies comprising human gamma-1 heavy chain constant regions comprising such an Asp and Leu and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.In an embodiment, said mutation is I474V.\",\n \"In another embodiment, said mutation is E670G.\",\n \"An example provides:— A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 in SEQ ID NO: 1, wherein the antibody or fragment comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 and a Leu corresponding to position 206 of SEQ ID NO: 42 and wherein said human comprises (i) an IGHG1*01 human heavy chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V in SEQ ID NO: 1.Optionally, the antibody or fragment comprises a IGHG1*01 human heavy chain constant region.\",\n \"Another example provides:— A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 and a Leu corresponding to position 206 of SEQ ID NO: 42 and wherein said human comprises (i) an IGHG1*01 human heavy chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation E670G in SEQ ID NO: 1.Optionally, the antibody or fragment comprises an IGHG1*01 human heavy chain constant region.\",\n \"In an example, said antibody or antibody fragment has been determined to specifically bind a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 or E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 and a Leu corresponding to position 206 of SEQ ID NO: 42 and wherein said human comprises (i) an IGHG1*01 human heavy chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.2.The method of paragraph 1, comprising, before said administering, selecting a human comprising said nucleotide sequence of (ii), wherein the human is the human of paragraph 1.3.The method of paragraph 1 or 2, wherein the antibody comprises a human gamma-1 heavy chain constant region that comprises an Asp corresponding to position 204 of SEQ ID NO: 42 and a Leu corresponding to position 206 of SEQ ID NO: 42.4.The method of paragraph 1, 2 or 3, wherein the antibody comprises an IGHG1*01 human heavy chain constant region.\",\n \"5.The method of any one of paragraphs 1 to 4, wherein the human has been determined to comprise the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1 and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein encoded by the nucleotide sequence of SEQ ID NO: 29 or 30.6.The method of any one of paragraphs 1 to 5, comprising the step of determining that the human comprises the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein comprising said mutation I474V or E670G, optionally, wherein the determining step is performed before administration of the antibody to the human.\",\n \"7.The method of paragraph 6, wherein the step of determining comprises assaying a biological sample from the human for a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.8.The method of paragraph 7, wherein the assaying comprises contacting the biological sample with a. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides that can specifically hybridize to and identify in the biological sample a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or that specifically hybridizes to an antisense of said sequence, wherein said nucleic acid hybridizes to at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 or hybridizes to an antisense sequence thereby forming a complex when at least one nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and/or b. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides of a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or comprising an antisense sequence of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 thereby forming a complex when the nucleotide sequence encoding the PCSK9 that comprises a C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and detecting the presence or absence of the complex, wherein detecting the presence of the complex determines that the human comprises the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.9.The method of paragraph 7 or 8, wherein the assaying comprises nucleic acid amplification and optionally one or more methods selected from sequencing, next generation sequencing, nucleic acid hybridization, and allele-specific amplification and/or wherein the assaying is performed in a multiplex format.\",\n \"10.The method of any one of paragraphs 1 to 9, wherein said human is or has been further determined to be substantially resistant to statin treatment.\",\n \"11.The method of any one of paragraphs 1 to 10, wherein said human is receiving or has received statin treatment or has reduced responsiveness to statin treatment.\",\n \"12.The method of paragraph 10 or 11, wherein said antibody or antibody fragment is administered to the human separately or simultaneously with said statin treatment.\",\n \"13.The method of any one of paragraphs 7 to 9, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine and/or saliva of said human.\",\n \"14.The method of any one of paragraphs 1 to 13, wherein said human is indicated as heterozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising said mutation I474V or E670G, optionally, wherein said human is further indicated as comprising the nucleotide sequence of SEQ ID NO: 28, or said human is indicated as homozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.15.The method of any one of paragraphs 1 to 14, wherein said human has been diagnosed with at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.\",\n \"16.The method of any one of paragraphs 1 to 15, wherein said antibody or antibody fragment treats or reduces the risk in said human of at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.\",\n \"17.The method of any one of paragraphs 1 to 16, wherein the nucleotide sequence is SEQ ID NO: 29 or 30.18.The method of any one of paragraphs 1 to 17, wherein said antibody or antibody fragment is administered by intravenous or subcutaneous administration and/or is comprised in an injectable preparation.\",\n \"Further exemplary ligands are in the paragraphs 1-17 as follows.\",\n \"1.An antibody or antibody fragment for use in a method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, wherein the antibody comprises a human gamma-2 heavy chain constant region that comprises an amino acid selected from the group consisting of a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44, a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44, and the antibody or fragment specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) amino acid sequence that comprises a C-terminal domain comprising a mutation I474V or E670G in SEQ ID NO: 1, wherein the human comprises a nucleotide sequence encoding said amino acid sequence and comprises an IGHG2*01 human heavy chain constant region gene segment, or the human expresses antibodies comprising human gamma-2 constant regions comprising such a Pro, Asn, Phe, Val and Ala.\",\n \"In an embodiment, said mutation is I474V.\",\n \"In another embodiment, said mutation is E670G.\",\n \"An example provides:— An antibody or antibody fragment for use in a method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, wherein the antibody comprises a human gamma-2 heavy chain constant region that comprises a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44, a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44, and the antibody or fragment specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) amino acid sequence that comprises a C-terminal domain comprising a mutation I474V in SEQ ID NO: 1, wherein the human comprises a nucleotide sequence encoding said amino acid sequence and comprises an IGHG2*01 human heavy chain constant region gene segment.\",\n \"Optionally, the antibody or fragment comprises an IGHG2*01 human heavy chain constant region.\",\n \"Another example provides:— An antibody or antibody fragment for use in a method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, wherein the antibody comprises a human gamma-2 heavy chain constant region that comprises a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44, a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44, and the antibody or fragment specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) amino acid sequence that comprises a C-terminal domain comprising a mutation E670G in SEQ ID NO: 1, wherein the human comprises a nucleotide sequence encoding said amino acid sequence and comprises an IGHG2*01 human heavy chain constant region gene segment.\",\n \"Optionally, the antibody or fragment comprises an IGHG2*01 human heavy chain constant region.\",\n \"In an example, said antibody or antibody fragment has been determined to specifically bind a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 or E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human gamma-2 heavy chain constant region that comprises a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44, a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44 and wherein said human comprises (i) an IGHG2*01 human heavy chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.2.The antibody or antibody fragment of paragraph 1, wherein the antibody comprises a human gamma-2 heavy chain constant region that comprises a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44, a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44.3.The antibody or antibody fragment of paragraph 1 or 2, wherein the antibody comprises an IGHG2*01 human heavy chain constant region.\",\n \"4.The antibody or antibody fragment of any one of paragraphs 1 to 3, wherein the human has been determined to comprise the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1 and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein encoded by the nucleotide sequence of SEQ ID NO: 29 or 30.5.The antibody or antibody fragment of any one of paragraphs 1 to 4, the method comprising the step of determining that the human comprises the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein comprising said mutation I474V or E670G, optionally, wherein the determining step is performed before administration of the antibody to the human.\",\n \"6.The antibody or antibody fragment of paragraph 5, wherein the step of determining comprises assaying a biological sample from the human for a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.7.The antibody or antibody fragment of paragraph 6, wherein the assaying comprises contacting the biological sample with a. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides that can specifically hybridize to and identify in the biological sample a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or that specifically hybridizes to an antisense of said sequence, wherein said nucleic acid hybridizes to at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 or hybridizes to an antisense sequence thereby forming a complex when at least one nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and/or b. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides of a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or comprising an antisense sequence of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 thereby forming a complex when the nucleotide sequence encoding the PCSK9 that comprises a C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and detecting the presence or absence of the complex, wherein detecting the presence of the complex determines that the human comprises the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.8.The antibody or antibody fragment of paragraph 6 or 7, wherein the assaying comprises nucleic acid amplification and optionally one or more methods selected from sequencing, next generation sequencing, nucleic acid hybridization, and allele-specific amplification and/or wherein the assaying is performed in a multiplex format.\",\n \"9.The antibody or antibody fragment of any one of paragraphs 1 to 8, wherein said antibody or antibody fragment is for administration to a human that is or has been further determined to be substantially resistant to statin treatment.\",\n \"10.The antibody or antibody fragment of any one of paragraphs 1 to 9, wherein antibody or antibody fragment is for administration to a human that is receiving or has received statin treatment or has reduced responsiveness to statin treatment.\",\n \"11.The antibody or antibody fragment of paragraph 9 or 10, wherein said antibody or antibody fragment is for administration to the human separately or simultaneously with said statin treatment.\",\n \"12.The antibody or antibody fragment of any one of paragraphs 6 to 8, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine and/or saliva of said human.\",\n \"13.The antibody or antibody fragment of any one of paragraphs 1 to 12, wherein said human is indicated as heterozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising a mutation I474V or E670G, optionally, wherein said human is further indicated as comprising the nucleotide sequence of SEQ ID NO: 28, or said human is indicated as homozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising a mutation I474V or E670G in SEQ ID NO: 1.14.The antibody or antibody fragment of any one of paragraphs 1 to 13, wherein said human has been diagnosed with at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.\",\n \"15.The antibody or antibody fragment of any one of paragraphs 1 to 14, wherein said antibody or antibody fragment treats or reduces the risk in said human of at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.\",\n \"16.The antibody or antibody fragment of any one of paragraphs 1 to 15, wherein the nucleotide sequence is SEQ ID NO: 29 or 30.17.The antibody or antibody fragment of any one of paragraphs 1 to 16, wherein said antibody or antibody fragment is for administration by intravenous or subcutaneous administration and/or is comprised in an injectable preparation.\",\n \"Further exemplary methods are in the paragraphs 1-18 as follows.\",\n \"1.A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 or E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human gamma-2 heavy chain constant region that comprises an amino acid selected from the group consisting of a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44, a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44 and wherein said human comprises (i) an IGHG2*01 human heavy chain constant region gene segment, or the human expresses antibodies comprising human gamma-2 heavy chain constant regions comprising such a Pro, Asn, Phe, Val and Ala and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.In an embodiment, said mutation is I474V.\",\n \"In another embodiment, said mutation is E670G.\",\n \"An example provides:— A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 in SEQ ID NO: 1, wherein the antibody or fragment comprises a human gamma-2 heavy chain constant region that comprises a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44, a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44 and wherein said human comprises (i) an IGHG2*01 human heavy chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V in SEQ ID NO: 1.Optionally, the antibody or fragment comprises an IGHG2*01 human heavy chain constant region.\",\n \"Another example provides:— A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human gamma-2 heavy chain constant region that comprises a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44, a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44 and wherein said human comprises (i) an IGHG2*01 human heavy chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation E670G in SEQ ID NO: 1.Optionally, the antibody or fragment comprises an IGHG2*01 human heavy chain constant region.\",\n \"In an example, said antibody or antibody fragment has been determined to specifically bind a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 or E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human gamma-2 heavy chain constant region that comprises a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44, a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44 and wherein said human comprises (i) an IGHG2*01 human heavy chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.2.The method of paragraph 1, comprising, before said administering, selecting said human comprising said nucleotide sequence of (ii).\",\n \"3.The method of paragraph 1 or 2, wherein the antibody comprises a human gamma-1 heavy chain constant region that comprises a Pro corresponding to position 72 of SEQ ID NO: 44, an Asn corresponding to position 75 of SEQ ID NO: 44, a Phe corresponding to position 76 of SEQ ID NO: 44, a Val corresponding to position 161 of SEQ ID NO: 44 and an Ala corresponding to position 257 of SEQ ID NO: 44.4.The method of paragraph 1, 2 or 3, wherein the antibody comprises an IGHG2*01 human heavy chain constant region.\",\n \"5.The method of any one of paragraphs 1 to 4, wherein the human has been determined to comprise the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1 and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein encoded by the nucleotide sequence of SEQ ID NO: 29 or 30.6.The method of any one of paragraphs 1 to 5, comprising the step of determining that the human comprises the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein comprising said mutation I474V or E670G, optionally, wherein the determining step is performed before administration of the antibody to the human.\",\n \"7.The method of paragraph 6, wherein the step of determining comprises assaying a biological sample from the human for a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.8.The method of paragraph 7, wherein the assaying comprises contacting the biological sample with a. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides that can specifically hybridize to and identify in the biological sample a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or that specifically hybridizes to an antisense of said sequence, wherein said nucleic acid hybridizes to at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 or hybridizes to an antisense sequence thereby forming a complex when at least one nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and/or b. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides of a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or comprising an antisense sequence of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 thereby forming a complex when the nucleotide sequence encoding the PCSK9 that comprises a C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and detecting the presence or absence of the complex, wherein detecting the presence of the complex determines that the human comprises the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.9.The method of paragraph 7 or 8, wherein the assaying comprises nucleic acid amplification and optionally one or more methods selected from sequencing, next generation sequencing, nucleic acid hybridization, and allele-specific amplification and/or wherein the assaying is performed in a multiplex format.\",\n \"10.The method of any one of paragraphs 1 to 9, wherein said human is or has been further determined to be substantially resistant to statin treatment.\",\n \"11.The method of any one of paragraphs 1 to 10, wherein said human is receiving or has received statin treatment or has reduced responsiveness to statin treatment.\",\n \"12.The method of paragraph 10 or 11, wherein said antibody or antibody fragment is administered to the human separately or simultaneously with said statin treatment.\",\n \"13.The method of any one of paragraphs 7 to 9, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine and/or saliva of said human.\",\n \"14.The method of any one of paragraphs 1 to 13, wherein said human is indicated as heterozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising said mutation I474V or E670G, optionally, wherein said human is further indicated as comprising the nucleotide sequence of SEQ ID NO: 28, or said human is indicated as homozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.15.The method of any one of paragraphs 1 to 14, wherein said human has been diagnosed with at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.\",\n \"16.The method of any one of paragraphs 1 to 15, wherein said antibody or antibody fragment treats or reduces the risk in said human of at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.\",\n \"17.The method of any one of paragraphs 1 to 16, wherein the nucleotide sequence is SEQ ID NO: 29 or 30.18.The method of any one of paragraphs 1 to 17, wherein said antibody or antibody fragment is administered by intravenous or subcutaneous administration and/or is comprised in an injectable preparation.\",\n \"Further exemplary ligands are in the paragraphs 1-17 as follows.\",\n \"1.An antibody or antibody fragment for use in a method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, wherein the antibody or fragment comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 or a Cys corresponding to position 87 of SEQ ID NO: 50, and the antibody or fragment specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) amino acid sequence that comprises a C-terminal domain comprising a mutation I474V or E670G in SEQ ID NO: 1, wherein the human comprises a nucleotide sequence encoding said amino acid sequence and comprises an IGKC*01 human light chain constant region gene segment, or the human expresses antibodies comprising human kappa light chain constant regions comprising such an Val and Cys.\",\n \"In an embodiment, said mutation is I474V.\",\n \"In another embodiment, said mutation is E670G.\",\n \"An example provides:— An antibody or antibody fragment for use in a method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, wherein the antibody or fragment comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 and a Cys corresponding to position 87 of SEQ ID NO: 50, and the antibody or fragment specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) amino acid sequence that comprises a C-terminal domain comprising a mutation I474V in SEQ ID NO: 1, wherein the human comprises a nucleotide sequence encoding said amino acid sequence and comprises an IGKC*01 human light chain constant region gene segment.\",\n \"Optionally, the antibody or fragment comprises an IGKC*01 human light chain constant region.\",\n \"Another example provides:— An antibody or antibody fragment for use in a method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, wherein the antibody or fragment comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 and a Cys corresponding to position 87 of SEQ ID NO: 50, and the antibody or fragment specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) amino acid sequence that comprises a C-terminal domain comprising a mutation E670G in SEQ ID NO: 1, wherein the human comprises a nucleotide sequence encoding said amino acid sequence and comprises an IGKC*01 human light chain constant region gene segment.\",\n \"Optionally, the antibody or fragment comprises an IGKC*01 human light chain constant region.\",\n \"In an example, said antibody or antibody fragment has been determined to specifically bind a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 or E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 and a Cys corresponding to position 87 of SEQ ID NO: 50 and wherein said human comprises (i) an IGKC*01 human heavy chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.2.The antibody or antibody fragment of paragraph 1, wherein the antibody comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 or a Cys corresponding to position 87 of SEQ ID NO: 50.3.The antibody or antibody fragment of paragraph 1 or 2, wherein the antibody comprises an IGKC*01 human kappa chain constant region.\",\n \"4.The antibody or antibody fragment of any one of paragraphs 1 to 3, wherein the human has been determined to comprise the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1 and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein encoded by the nucleotide sequence of SEQ ID NO: 29 or 30.5.The antibody or antibody fragment of any one of paragraphs 1 to 4, the method comprising the step of determining that the human comprises the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein comprising said mutation I474V or E670G, optionally, wherein the determining step is performed before administration of the antibody to the human.\",\n \"6.The antibody or antibody fragment of paragraph 5, wherein the step of determining comprises assaying a biological sample from the human for a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.7.The antibody or antibody fragment of paragraph 6, wherein the assaying comprises contacting the biological sample with a. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides that can specifically hybridize to and identify in the biological sample a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or that specifically hybridizes to an antisense of said sequence, wherein said nucleic acid hybridizes to at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 or hybridizes to an antisense sequence thereby forming a complex when at least one nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and/or b. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides of a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or comprising an antisense sequence of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 thereby forming a complex when the nucleotide sequence encoding the PCSK9 that comprises a C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and detecting the presence or absence of the complex, wherein detecting the presence of the complex determines that the human comprises the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.8.The antibody or antibody fragment of paragraph 6 or 7, wherein the assaying comprises nucleic acid amplification and optionally one or more methods selected from sequencing, next generation sequencing, nucleic acid hybridization, and allele-specific amplification and/or wherein the assaying is performed in a multiplex format.\",\n \"9.The antibody or antibody fragment of any one of paragraphs 1 to 8, wherein said antibody or antibody fragment is for administration to a human that is or has been further determined to be substantially resistant to statin treatment.\",\n \"10.The antibody or antibody fragment of any one of paragraphs 1 to 9, wherein antibody or antibody fragment is for administration to a human that is receiving or has received statin treatment or has reduced responsiveness to statin treatment.\",\n \"11.The antibody or antibody fragment of paragraph 9 or 10, wherein said antibody or antibody fragment is for administration to the human separately or simultaneously with said statin treatment.\",\n \"12.The antibody or antibody fragment of any one of paragraphs 6 to 10, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine and/or saliva of said human.\",\n \"13.The antibody or antibody fragment of any one of paragraphs 1 to 12, wherein said human is indicated as heterozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising a mutation I474V or E670G, optionally, wherein said human is further indicated as comprising the nucleotide sequence of SEQ ID NO: 28, or said human is indicated as homozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising a mutation I474V or E670G in SEQ ID NO: 1.14.The antibody or antibody fragment of any one of paragraphs 1 to 13, wherein said human has been diagnosed with at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.\",\n \"15.The antibody or antibody fragment of any one of paragraphs 1 to 14, wherein said antibody or antibody fragment treats or reduces the risk in said human of at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.\",\n \"16.The antibody or antibody fragment of any one of paragraphs 1 to 15, wherein the nucleotide sequence is SEQ ID NO: 29 or 30.17.The antibody or antibody fragment of any one of paragraphs 1 to 16, wherein said antibody or antibody fragment is for administration by intravenous or subcutaneous administration and/or is comprised in an injectable preparation.\",\n \"Further exemplary methods are in the paragraphs 1-18 as follows.\",\n \"1.A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 or E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 or a Cys corresponding to position 87 of SEQ ID NO: 50 and wherein said human comprises (i) an IGKC*01 human light chain constant region gene segment, or the human expresses antibodies comprising human kappa light chain constant regions comprising such an Val and Cys and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.In an embodiment, said mutation is I474V.\",\n \"In another embodiment, said mutation is E670G.\",\n \"An example provides:— A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 in SEQ ID NO: 1, wherein the antibody or fragment comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 and a Cys corresponding to position 87 of SEQ ID NO: 50 and wherein said human comprises (i) an IGKC*01 human light chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V in SEQ ID NO: 1.Optionally, the antibody or fragment comprises an IGKC*01 human light chain constant region.\",\n \"Another example provides:— A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 and a Cys corresponding to position 87 of SEQ ID NO: 50 and wherein said human comprises (i) an IGKC*01 human light chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation E670G in SEQ ID NO: 1.Optionally, the antibody or fragment comprises an IGKC*01 human light chain constant region.\",\n \"In an example, said antibody or antibody fragment has been determined to specifically bind a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 or E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 and a Cys corresponding to position 87 of SEQ ID NO: 50 and wherein said human comprises (i) an IGKC*01 human heavy chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.2.The method of paragraph 1, comprising, before said administering, selecting said human comprising said nucleotide sequence of (ii).\",\n \"3.The method of paragraph 1 or 2, wherein the antibody comprises a human kappa light chain constant region that comprises a Val corresponding to position 84 of SEQ ID NO: 50 or a Cys corresponding to position 87 of SEQ ID NO: 50.4.The method of paragraph 1, 2 or 3, wherein the antibody comprises an IGKC*01 human kappa chain constant region.\",\n \"5.The method of any one of paragraphs 1 to 4, wherein the human has been determined to comprise the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1 and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein encoded by the nucleotide sequence of SEQ ID NO: 29 or 30.6.The method of any one of paragraphs 1 to 5, comprising the step of determining that the human comprises the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein comprising said mutation I474V or E670G, optionally, wherein the determining step is performed before administration of the antibody to the human.\",\n \"7.The method of paragraph 6, wherein the step of determining comprises assaying a biological sample from the human for a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.8.The method of paragraph 7, wherein the assaying comprises contacting the biological sample with a. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides that can specifically hybridize to and identify in the biological sample a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or that specifically hybridizes to an antisense of said sequence, wherein said nucleic acid hybridizes to at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 or hybridizes to an antisense sequence thereby forming a complex when at least one nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and/or b. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides of a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or comprising an antisense sequence of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 thereby forming a complex when the nucleotide sequence encoding the PCSK9 that comprises a C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and detecting the presence or absence of the complex, wherein detecting the presence of the complex determines that the human comprises the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.9.The method of paragraph 7 or 8, wherein the assaying comprises nucleic acid amplification and optionally one or more methods selected from sequencing, next generation sequencing, nucleic acid hybridization, and allele-specific amplification and/or wherein the assaying is performed in a multiplex format.\",\n \"10.The method of any one of paragraphs 1 to 9, wherein said human is or has been further determined to be substantially resistant to statin treatment.\",\n \"11.The method of any one of paragraphs 1 to 10, wherein said human is receiving or has received statin treatment or has reduced responsiveness to statin treatment.\",\n \"12.The method of paragraph 10 or 11, wherein said antibody or antibody fragment is administered to the human separately or simultaneously with said statin treatment.\",\n \"13.The method of any one of paragraphs 7 to 9, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine and/or saliva of said human.\",\n \"14.The method of any one of paragraphs 1 to 13, wherein said human is indicated as heterozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising said mutation I474V or E670G, optionally, wherein said human is further indicated as comprising the nucleotide sequence of SEQ ID NO: 28, or said human is indicated as homozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.15.The method of any one of paragraphs 1 to 14, wherein said human has been diagnosed with at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.\",\n \"16.The method of any one of paragraphs 1 to 15, wherein said antibody or antibody fragment treats or reduces the risk in said human of at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.\",\n \"17.The method of any one of paragraphs 1 to 16, wherein the nucleotide sequence is SEQ ID NO: 29 or 30.18.The method of any one of paragraphs 1 to 17, wherein said antibody or antibody fragment is administered by intravenous or subcutaneous administration and/or is comprised in an injectable preparation.\",\n \"Further exemplary ligands are in the paragraphs 1-15 as follows.\",\n \"1.An antibody or antibody fragment for use in a method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, wherein the antibody or fragment comprises a human IGLC2*01 lambda light chain constant region, and the antibody or fragment specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) amino acid sequence that comprises a C-terminal domain comprising a mutation I474V or E670G in SEQ ID NO: 1, wherein the human comprises a nucleotide sequence encoding said amino acid sequence and comprises a human IGLC2*01 lambda light chain constant region gene segment, or the human expresses antibodies comprising human IGLC2*01 lambda light chain constant regions.\",\n \"In an embodiment, said mutation is I474V.\",\n \"In another embodiment, said mutation is E670G.\",\n \"An example provides:— An antibody or antibody fragment for use in a method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, wherein the antibody or fragment comprises a human IGLC2*01 lambda light chain constant region, and the antibody or fragment specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) amino acid sequence that comprises a C-terminal domain comprising a mutation I474V in SEQ ID NO: 1, wherein the human comprises a nucleotide sequence encoding said amino acid sequence and comprises a human IGLC2*01 lambda light chain constant region gene segment.\",\n \"Optionally, the antibody or fragment comprises a human IGLC2*01 lambda light chain constant region.\",\n \"Another example provides:— An antibody or antibody fragment for use in a method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, wherein the antibody or fragment comprises a human IGLC2*01 lambda light chain constant region, and the antibody or fragment specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) amino acid sequence that comprises a C-terminal domain comprising a mutation E670G in SEQ ID NO: 1, wherein the human comprises a nucleotide sequence encoding said amino acid sequence and comprises a human IGLC2*01 lambda light chain constant region gene segment.\",\n \"Optionally, the antibody or fragment comprises a human IGLC2*01 lambda light chain constant region.\",\n \"In an example, said antibody or antibody fragment has been determined to specifically bind a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 or E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human IGLC2*01 lambda light chain constant region and wherein said human comprises (i) an IGLC2*01 human heavy chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.2.The antibody or antibody fragment of paragraph 1, wherein the human has been determined to comprise the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1 and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein encoded by the nucleotide sequence of SEQ ID NO: 29 or 30.3.The antibody or antibody fragment of paragraphs 1 or 2, the method comprising the step of determining that the human comprises the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein comprising said mutation I474V or E670G, optionally, wherein the determining step is performed before administration of the antibody to the human.\",\n \"4.The antibody or antibody fragment of paragraph 3, wherein the step of determining comprises assaying a biological sample from the human for a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.5.The antibody or antibody fragment of paragraph 4, wherein the assaying comprises contacting the biological sample with a. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides that can specifically hybridize to and identify in the biological sample a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or that specifically hybridizes to an antisense of said sequence, wherein said nucleic acid hybridizes to at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 or hybridizes to an antisense sequence thereby forming a complex when at least one nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and/or b. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides of a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or comprising an antisense sequence of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 thereby forming a complex when the nucleotide sequence encoding the PCSK9 that comprises a C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and detecting the presence or absence of the complex, wherein detecting the presence of the complex determines that the human comprises the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.6.The antibody or antibody fragment of paragraph 4 or 5, wherein the assaying comprises nucleic acid amplification and optionally one or more methods selected from sequencing, next generation sequencing, nucleic acid hybridization, and allele-specific amplification and/or wherein the assaying is performed in a multiplex format.\",\n \"7.The antibody or antibody fragment of any one of paragraphs 1 to 6, wherein said antibody or antibody fragment is for administration to a human that is or has been further determined to be substantially resistant to statin treatment.\",\n \"8.The antibody or antibody fragment of any one of paragraphs 1 to 7, wherein antibody or antibody fragment is for administration to a human that is receiving or has received statin treatment or has reduced responsiveness to statin treatment.\",\n \"9.The antibody or antibody fragment of paragraph 7 or 8, wherein said antibody or antibody fragment is for administration to the human separately or simultaneously with said statin treatment.\",\n \"10.The antibody or antibody fragment of any one of paragraphs 4 to 8, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine and/or saliva of said human.\",\n \"11.The antibody or antibody fragment of any one of paragraphs 1 to 10, wherein said human is indicated as heterozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising a mutation I474V or E670G, optionally, wherein said human is further indicated as comprising the nucleotide sequence of SEQ ID NO: 28, or said human is indicated as homozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising a mutation I1474V or E670G in SEQ ID NO: 1.12.The antibody or antibody fragment of any one of paragraphs 1 to 11, wherein said human has been diagnosed with at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.\",\n \"13.The antibody or antibody fragment of any one of paragraphs 1 to 12, wherein said antibody or antibody fragment treats or reduces the risk in said human of at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.\",\n \"14.The antibody or antibody fragment of any one of paragraphs 1 to 13, wherein the nucleotide sequence is SEQ ID NO: 29 or 30.15.The antibody or antibody fragment of any one of paragraphs 1 to 14, wherein said antibody or antibody fragment is for administration by intravenous or subcutaneous administration and/or is comprised in an injectable preparation.\",\n \"Further exemplary methods are in the paragraphs 1-16 as follows.\",\n \"1.A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 or E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human IGLC2*01 lambda light chain constant region and wherein said human comprises (i) an IGLC2*01 human light chain constant region gene segment, or the human expresses antibodies comprising a human IGLC2*01 lambda light chain constant regions and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.In an embodiment, said mutation is I474V.\",\n \"In another embodiment, said mutation is E670G.\",\n \"An example provides:— A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 in SEQ ID NO: 1, wherein the antibody or fragment comprises a human IGLC2*01 lambda light chain constant region and wherein said human comprises (i) an IGLC2*01 human light chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V in SEQ ID NO: 1.Optionally, the antibody or fragment comprises an IGLC2*01 human light chain constant region.\",\n \"Another example provides:— A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human IGLC2*01 lambda light chain constant region and wherein said human comprises (i) an IGLC2*01 human light chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation E670G in SEQ ID NO: 1.Optionally, the antibody or fragment comprises an IGLC2*01 human light chain constant region.\",\n \"In an example, said antibody or antibody fragment has been determined to specifically bind a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 or E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human IGLC2*01 lambda light chain constant region and wherein said human comprises (i) an IGLC2*01 human heavy chain constant region gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1 2.The method of paragraph 1, comprising, before said administering, selecting said human comprising said nucleotide sequence of (ii).\",\n \"3.The method of paragraph 1 or 2, wherein the human has been determined to comprise the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1 and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein encoded by the nucleotide sequence of SEQ ID NO: 29 or 30.4.The method of any one of paragraphs 1 to 3, comprising the step of determining that the human comprises the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein comprising said mutation I474V or E670G, optionally, wherein the determining step is performed before administration of the antibody to the human.\",\n \"5.The method of paragraph 4, wherein the step of determining comprises assaying a biological sample from the human for a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.6.The method of paragraph 5, wherein the assaying comprises contacting the biological sample with a. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides that can specifically hybridize to and identify in the biological sample a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or that specifically hybridizes to an antisense of said sequence, wherein said nucleic acid hybridizes to at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 or hybridizes to an antisense sequence thereby forming a complex when at least one nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and/or b. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides of a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or comprising an antisense sequence of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 thereby forming a complex when the nucleotide sequence encoding the PCSK9 that comprises a C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and detecting the presence or absence of the complex, wherein detecting the presence of the complex determines that the human comprises the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.7.The method of paragraph 5 or 6, wherein the assaying comprises nucleic acid amplification and optionally one or more methods selected from sequencing, next generation sequencing, nucleic acid hybridization, and allele-specific amplification and/or wherein the assaying is performed in a multiplex format.\",\n \"8.The method of any one of paragraphs 1 to 7, wherein said human is or has been further determined to be substantially resistant to statin treatment.\",\n \"9.The method of any one of paragraphs 1 to 8, wherein said human is receiving or has received statin treatment or has reduced responsiveness to statin treatment.\",\n \"10.The method of paragraph 8 or 9, wherein said antibody or antibody fragment is administered to the human separately or simultaneously with said statin treatment.\",\n \"11.The method of any one of paragraphs 5 to 7, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine and/or saliva of said human.\",\n \"12.The method of any one of paragraphs 1 to 11, wherein said human is indicated as heterozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising said mutation I474V or E670G, optionally, wherein said human is further indicated as comprising the nucleotide sequence of SEQ ID NO: 28, or said human is indicated as homozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.13.The method of any one of paragraphs 1 to 12, wherein said human has been diagnosed with at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.\",\n \"14.The method of any one of paragraphs 1 to 13, wherein said antibody or antibody fragment treats or reduces the risk in said human of at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.\",\n \"15.The method of any one of paragraphs 1 to 14, wherein the nucleotide sequence is SEQ ID NO: 29 or 30.16.The method of any one of paragraphs 1 to 15, wherein said antibody or antibody fragment is administered by intravenous or subcutaneous administration and/or is comprised in an injectable preparation.\",\n \"Further exemplary ligands are in the paragraphs 1-15 as follows.\",\n \"1.An antibody or antibody fragment for use in a method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, wherein the antibody or fragment comprises a human variable domain that is derived from the recombination of a human VH gene segment, a human D gene segment and a human JH gene segment, wherein the VH gene segment is as defined in any one of clauses 80 to 90, and the antibody or fragment specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) amino acid sequence that comprises a C-terminal domain comprising a mutation I474V or E670G in SEQ ID NO: 1, wherein the human comprises a nucleotide sequence encoding said amino acid sequence, and comprises said VH gene segment or expresses antibodies comprising VH domains that are derived from the recombination of said human VH gene segment, a human D gene segment and a human JH gene segment.\",\n \"In an embodiment, said mutation is I474V.\",\n \"In another embodiment, said mutation is E670G.\",\n \"2.The antibody or antibody fragment of paragraph 1, wherein the human has been determined to comprise the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1 and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein encoded by the nucleotide sequence of SEQ ID NO: 29 or 30.3.The antibody or antibody fragment of paragraphs 1 or 2, the method comprising the step of determining that the human comprises the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein comprising said mutation I474V or E670G, optionally, wherein the determining step is performed before administration of the antibody to the human.\",\n \"4.The antibody or antibody fragment of paragraph 3, wherein the step of determining comprises assaying a biological sample from the human for a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.5.The antibody or antibody fragment of paragraph 4, wherein the assaying comprises contacting the biological sample with a. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides that can specifically hybridize to and identify in the biological sample a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or that specifically hybridizes to an antisense of said sequence, wherein said nucleic acid hybridizes to at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 or hybridizes to an antisense sequence thereby forming a complex when at least one nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and/or b. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides of a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or comprising an antisense sequence of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 thereby forming a complex when the nucleotide sequence encoding the PCSK9 that comprises a C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and detecting the presence or absence of the complex, wherein detecting the presence of the complex determines that the human comprises the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.6.The antibody or antibody fragment of paragraph 4 or 5, wherein the assaying comprises nucleic acid amplification and optionally one or more methods selected from sequencing, next generation sequencing, nucleic acid hybridization, and allele-specific amplification and/or wherein the assaying is performed in a multiplex format.\",\n \"7.The antibody or antibody fragment of any one of paragraphs 1 to 6, wherein said antibody or antibody fragment is for administration to a human that is or has been further determined to be substantially resistant to statin treatment.\",\n \"8.The antibody or antibody fragment of any one of paragraphs 1 to 7, wherein antibody or antibody fragment is for administration to a human that is receiving or has received statin treatment or has reduced responsiveness to statin treatment.\",\n \"9.The antibody or antibody fragment of paragraph 7 or 8, wherein said antibody or antibody fragment is for administration to the human separately or simultaneously with said statin treatment.\",\n \"10.The antibody or antibody fragment of any one of paragraphs 4 to 8, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine and/or saliva of said human.\",\n \"11.The antibody or antibody fragment of any one of paragraphs 1 to 10, wherein said human is indicated as heterozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising a mutation I474V or E670G, optionally, wherein said human is further indicated as comprising the nucleotide sequence of SEQ ID NO: 28, or said human is indicated as homozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising a mutation I474V or E670G in SEQ ID NO: 1.12.The antibody or antibody fragment of any one of paragraphs 1 to 11, wherein said human has been diagnosed with at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.\",\n \"13.The antibody or antibody fragment of any one of paragraphs 1 to 12, wherein said antibody or antibody fragment treats or reduces the risk in said human of at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.\",\n \"14.The antibody or antibody fragment of any one of paragraphs 1 to 13, wherein the nucleotide sequence is SEQ ID NO: 29 or 30.15.The antibody or antibody fragment of any one of paragraphs 1 to 14, wherein said antibody or antibody fragment is for administration by intravenous or subcutaneous administration and/or is comprised in an injectable preparation.\",\n \"Further exemplary methods are in the paragraphs 1-16 as follows.\",\n \"1.A method of reducing cholesterol level or maintaining previously reduced cholesterol level in a human in need thereof, the method comprising administering to said human an antibody or antibody fragment that specifically binds a proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising a mutation I474 or E670G in SEQ ID NO: 1, wherein the antibody or fragment comprises a human variable domain that is derived from the recombination of a human VH gene segment, a human D gene segment and a human JH gene segment, wherein the VH gene segment is as defined in any one of clauses 80 to 90 and wherein said human comprises (i) comprises said VH gene segment or expresses antibodies comprising VH domains that are derived from the recombination of said human VH gene segment, a human D gene segment and a human JH gene segment and (ii) a nucleotide sequence encoding said proprotein convertase subtilisin/kexin type 9 (PCSK9) that comprises a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.In an embodiment, said mutation is I474V.\",\n \"In another embodiment, said mutation is E670G.\",\n \"2.The method of paragraph 1, comprising, before said administering, selecting said human comprising said nucleotide sequence of (ii).\",\n \"3.The method of paragraph 1 or 2, wherein the human has been determined to comprise the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1 and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein encoded by the nucleotide sequence of SEQ ID NO: 29 or 30.4.The method of any one of paragraphs 1 to 3, comprising the step of determining that the human comprises the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein comprising said mutation I474V or E670G, optionally, wherein the determining step is performed before administration of the antibody to the human.\",\n \"5.The method of paragraph 4, wherein the step of determining comprises assaying a biological sample from the human for a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.6.The method of paragraph 5, wherein the assaying comprises contacting the biological sample with a. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides that can specifically hybridize to and identify in the biological sample a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or that specifically hybridizes to an antisense of said sequence, wherein said nucleic acid hybridizes to at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 or hybridizes to an antisense sequence thereby forming a complex when at least one nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and/or b. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides of a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or comprising an antisense sequence of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 thereby forming a complex when the nucleotide sequence encoding the PCSK9 that comprises a C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and detecting the presence or absence of the complex, wherein detecting the presence of the complex determines that the human comprises the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.7.The method of paragraph 5 or 6, wherein the assaying comprises nucleic acid amplification and optionally one or more methods selected from sequencing, next generation sequencing, nucleic acid hybridization, and allele-specific amplification and/or wherein the assaying is performed in a multiplex format.\",\n \"8.The method of any one of paragraphs 1 to 7, wherein said human is or has been further determined to be substantially resistant to statin treatment.\",\n \"9.The method of any one of paragraphs 1 to 8, wherein said human is receiving or has received statin treatment or has reduced responsiveness to statin treatment.\",\n \"10.The method of paragraph 8 or 9, wherein said antibody or antibody fragment is administered to the human separately or simultaneously with said statin treatment.\",\n \"11.The method of any one of paragraphs 5 to 7, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine and/or saliva of said human.\",\n \"12.The method of any one of paragraphs 1 to 11, wherein said human is indicated as heterozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising said mutation I474V or E670G, optionally, wherein said human is further indicated as comprising the nucleotide sequence of SEQ ID NO: 28, or said human is indicated as homozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.13.The method of any one of paragraphs 1 to 12, wherein said human has been diagnosed with at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.\",\n \"14.The method of any one of paragraphs 1 to 13, wherein said antibody or antibody fragment treats or reduces the risk in said human of at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.\",\n \"15.The method of any one of paragraphs 1 to 14, wherein the nucleotide sequence is SEQ ID NO: 29 or 30.16.The method of any one of paragraphs 1 to 15, wherein said antibody or antibody fragment is administered by intravenous or subcutaneous administration and/or is comprised in an injectable preparation.\",\n \"Regimens A: The invention further provides the following regimens, ligands and kits.\",\n \"1.A method for treating a human PCSK9-mediated disease or condition in a human by targeting a rare variant human PCSK9, the method comprising administering to the human a ligand (eg, an antibody or fragment) that has been determined to specifically bind to said PCSK9 variant; wherein the human expresses said PCSK9 variant or the genome of the human comprises a nucleotide sequence encoding said PCSK9 variant; wherein said human is treated for said disease or condition.\",\n \"The variant PCSK9 can, for example, be any rare variant as described herein.\",\n \"For example, there is provided: 1a.\",\n \"A method for treating a PCSK9-mediated disease or condition in a human by targeting a PCSK9 that comprises a C-terminal domain amino acid polymorphism (compared to SEQ ID NO: 1), the method comprising administering to the human a ligand (eg, an antibody or fragment) that has been determined to specifically bind to a PCSK9 comprising a C-terminal domain comprising I474V or 670G (numbering according to SEQ ID NO: 1); wherein the human expresses said PCSK9 or the genome of the human comprises a nucleotide sequence encoding said PCSK9; wherein said human is treated for said disease or condition.\",\n \"In an embodiment, determination of said specific binding is by reference to binding assay data, eg, as determined using SPR or ELISA.\",\n \"Determination may, for example, be by reference to information in a printed publication, eg, with knowledge of data presented in the present or another patent application or in a journal article.\",\n \"Once armed with such knowledge (eg, in the absence of further testing of binding), the skilled person is able—by direction of the present invention—to treat a relevant human whose genotype or phenotype matches the binding specificity of the ligand.\",\n \"The antibody or fragment can be according to any configuration, example, embodiment, aspect, clause or paragraph herein.\",\n \"In an embodiment, the method comprises, before said administering, selecting a human comprising said nucleotide sequence encoding the PCSK9, wherein the human is said human in clause 1 (eg, 1a).\",\n \"2.The method of clause 1, comprising before said administering the step of determining that the ligand specifically binds to said PCSK9, eg, using SPR or ELISA.\",\n \"3.The method of clause 1 or 2, wherein the specific binding to said PCSK9 is binding with a dissociation constant (Kd) of 1 nM or less, eg, 100, 10 or 1 pM or less.\",\n \"4.The method of any of clauses 1 to 3 (eg, clause 1a), wherein the condition is elevated LDL-cholesterol or is caused by elevated LDL-cholesterol.\",\n \"5.The method of clause 4 (eg, when dependent from clause 1a), wherein the condition is selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.\",\n \"6.The method of any one of clauses 1 to 5 (eg, when dependent from clause 1a), wherein the human has been determined to comprise the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1 and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein encoded by the nucleotide sequence of SEQ ID NO: 29 or 30.7.The method of any one of clauses 1 to 6 (eg, when dependent from clause 1a), comprising the step of determining that the human comprises the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein comprising said mutation I474V or E670G, optionally, wherein the determining step is performed before administration of the antibody to the human.\",\n \"8.The method of clause 7, wherein the step of determining comprises assaying a biological sample from the human for a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.9.The method of clause 8, wherein the assaying comprises contacting the biological sample with a. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides that can specifically hybridize to and identify in the biological sample a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or that specifically hybridizes to an antisense of said sequence, wherein said nucleic acid hybridizes to at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 or hybridizes to an antisense sequence thereby forming a complex when at least one nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and/or b. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides of a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or comprising an antisense sequence of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 thereby forming a complex when the nucleotide sequence encoding the PCSK9 that comprises a C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and detecting the presence or absence of the complex, wherein detecting the presence of the complex determines that the human comprises the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.10.The method of clause 8 or 9, wherein the assaying comprises nucleic acid amplification and optionally one or more methods selected from sequencing, next generation sequencing, nucleic acid hybridization, and allele-specific amplification and/or wherein the assaying is performed in a multiplex format.\",\n \"11.The method of any one of clauses 1 to 10, wherein said human is or has been further determined to be substantially resistant to statin treatment.\",\n \"12.The method of any one of clauses 1 to 11, wherein said human is receiving or has received statin treatment or has reduced responsiveness to statin treatment.\",\n \"13.The method of clauses 11 or 12, wherein said antibody or antibody fragment is administered to the human separately or simultaneously with said statin treatment.\",\n \"14.The method of any one of clauses 8 to 10, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine and/or saliva of said human.\",\n \"15.The method of any one of clauses 1 to 14, wherein said human is indicated as heterozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising said mutation I474V or E670G, optionally, wherein said human is further indicated as comprising the nucleotide sequence of SEQ ID NO: 28, or said human is indicated as homozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.16.The method of any one of clauses 1 to 15, wherein said human has been diagnosed with at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.\",\n \"17.The method of any one of clauses 1 to 16, wherein said antibody or antibody fragment treats or reduces the risk in said human of at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.\",\n \"18.The method of any one of clauses 1 to 17, wherein the nucleotide sequence is SEQ ID NO: 29 or 30.19.The method of any one of clauses 1 to 18, wherein said antibody or antibody fragment is administered by intravenous or subcutaneous administration and/or is comprised in an injectable preparation.\",\n \"20.A ligand (eg, an antibody or fragment) for use in the method of any one of clauses 1 to 19, wherein the ligand specifically binds the PCSK9.21.A kit comprising the ligand of clause 20 and instructions for carrying out the method of any one of clauses 1 to 19.B: The invention further provides the following regimens, ligands and kits.\",\n \"1.A method of reducing cholesterol level or maintaining a previously reduced cholesterol level in a human in need thereof, the method comprising:— a.\",\n \"Carrying out an initial treatment of said human for an initial treatment period by administering an anti-human PCSK9 ligand (eg, an antibody or fragment) to said human, wherein (i) the ligand has been determined to specifically bind to a PCSK9 comprising a C-terminal domain comprising I474V or 670G (numbering according to SEQ ID NO: 1); (ii) the human expresses said PCSK9 or the genome of the human comprises a nucleotide sequence encoding said PCSK9 and (iii) the human has received or is receiving statin treatment to lower or maintain cholesterol level; wherein the initial treatment comprises the administration of a single or multiple doses of the ligand to the human; b.\",\n \"Determining to (i) terminate statin treatment (ii) keep the human off statin treatment; or (iii) reduce statin treatment after said initial treatment period; and c. Continuing to administer the ligand to said patient after said time period has expired, thereby reducing cholesterol level or maintaining a previously reduced cholesterol level in said human.\",\n \"In an embodiment, determination of said specific binding is by reference to binding assay data, eg, as determined using SPR or ELISA.\",\n \"Determination may, for example, be by reference to information in a printed publication, eg, with knowledge of data presented in the present or another patent application or in a journal article.\",\n \"Once armed with such knowledge (eg, in the absence of further testing of binding), the skilled person is able—by direction of the present invention—to treat a relevant human whose genotype or phenotype matches the binding specificity of the ligand.\",\n \"The antibody or fragment can be according to any configuration, example, embodiment, aspect, clause or paragraph herein.\",\n \"A pharmaceutically-effective amount of said ligand is administered.\",\n \"In an embodiment, the method comprises, before said administering, selecting a human comprising said nucleotide sequence encoding the PCSK9, wherein the human is said human recited in clause 1.In an example, the initial treatment period is 7 days, 14 days, 21 days, 28 days, a month, two months, three months, four months, five months, six months, seven months, eight months, nine months or a year.\",\n \"2.The method of clause 1, wherein the human has or is suffering from statin-associated memory loss or a statin-associated neurodegenerative condition, or has or is at increased risk of diabetes (eg, statin-associated diabetes).\",\n \"3.The method of clause 1 or 2, comprising, before said initial treatment, the step of determining that the human has or is suffering from statin-associated memory loss or a statin-associated neurodegenerative condition, or has or is at increased risk of diabetes (eg, statin-associated diabetes).\",\n \"4.The method of clause 2 or 3, comprising, after step (b) (eg, during step (c)) determining that the memory loss or said neurodegenerative condition has improved.\",\n \"5.The method of any one of clauses 1 to 4, wherein said human is over 40 years of age (eg, 50 or over, 55 or over, 60 or over, 65 or over, or 70 or over).\",\n \"6.The method of any one of clauses 1 to 5, wherein step (c) comprises determining to increase the doses of said ligand to be administered after said initial treatment period and administering said increased doses to said human.\",\n \"7.The method of any one of clauses 1 to 6, wherein step (b) comprises determining that the human is intolerant or refactory to treatment by a statin.\",\n \"8.The method of any one of clauses 1 to 7, wherein the initial treatment comprises the administration of a statin, fenofibrate (eg, Tricor™ or Lofibra™) or ezetimibe to the human in addition to the ligand.\",\n \"9.The method of any one of clauses 1 to 8, wherein step (b) comprises terminating or reducing statin, fenofibrate (eg, Tricor™ or Lofibra™) or ezetimibe treatment during step (c).\",\n \"10.The method of any one of clauses 1 to 9, comprising increasing (ie, increasing compared to the initial treatment dose) the ligand dose during step (c).\",\n \"11.The method of any one of clauses 1 to 10, wherein the human has received high dose statin treatment prior to the initial treatment, and wherein step (c) comprises administering a lower (eg, a medium or low) dose statin treatment in addition to said ligand.\",\n \"The skilled person is familiar with the meaning of high, medium and low dose treatments (and how to determine according to each patient, eg, the patient's body mass).\",\n \"For example, the statin is selected from rosuvastatin, atorvastatin and simvastatin.\",\n \"For example daily statin doses are as follows:—Low 10 to 20 mg (eg, 10 mg); medium>20 and <60 mg (eg, 40 mg); high 60-100 mg (eg, 80 mg).\",\n \"12.The method of any one of clauses 1 to 10, wherein the human has received medium dose statin treatment prior to the initial treatment, and wherein step (c) comprises administering a lower (eg, a low) dose statin treatment or no statin in addition to said ligand.\",\n \"13.The method of any one of clauses 1 to 10, wherein the human has received low dose statin treatment prior to the initial treatment, and wherein step (c) comprises administering no statin in addition to said ligand.\",\n \"14.The method of any one of clauses 1 to 13, comprising, before the initial treatment, the step of determining that the ligand specifically binds to said PCSK9, eg, using SPR or ELISA.\",\n \"15.The method of any one of clauses 1 to 14, wherein the specific binding to said PCSK9 is binding with a dissociation constant (Kd) of 1 nM or less, eg, 100, 10 or 1 pM or less.\",\n \"16.The method of any of clauses 1 to 15, wherein the human is at risk of or suffering from a condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.\",\n \"17.The method of clause 16, wherein step (c) treats or reduces the risk of said condition in the human.\",\n \"18.The method of any one of clauses 1 to 17, wherein the human has been determined to comprise the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1 and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein encoded by the nucleotide sequence of SEQ ID NO: 29 or 30.19.The method of any one of clauses 1 to 18, comprising the step of determining that the human comprises the nucleotide sequence that encodes a PCSK9 comprising a C-terminal domain comprising said mutation I474V or E670G and/or a proprotein convertase subtilisin/kexin type 9 (PCSK9) variant protein comprising said mutation I474V or E670G, optionally, wherein the determining step is performed before administration of the antibody to the human.\",\n \"20.The method of clause 19, wherein the step of determining comprises assaying a biological sample from the human for a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.21.The method of clause 20, wherein the assaying comprises contacting the biological sample with a. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides that can specifically hybridize to and identify in the biological sample a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or that specifically hybridizes to an antisense of said sequence, wherein said nucleic acid hybridizes to at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 or hybridizes to an antisense sequence thereby forming a complex when at least one nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and/or b. at least one oligonucleotide probe comprising a sequence of at least 10 contiguous nucleotides of a nucleotide sequence encoding the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 or comprising an antisense sequence of said contiguous nucleotides, wherein said sequence of contiguous nucleotides comprises at least one nucleotide present in said selected sequence which is not present in SEQ ID NO: 28 thereby forming a complex when the nucleotide sequence encoding the PCSK9 that comprises a C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1 is present; and detecting the presence or absence of the complex, wherein detecting the presence of the complex determines that the human comprises the PCSK9 that comprises the C-terminal domain comprising the mutation I474V or E670G in SEQ ID NO: 1.22.The method of clause 20 or 21, wherein the assaying comprises nucleic acid amplification and optionally one or more methods selected from sequencing, next generation sequencing, nucleic acid hybridization, and allele-specific amplification and/or wherein the assaying is performed in a multiplex format.\",\n \"23.The method of any one of clauses 1 to 22, wherein said human is or has been further determined to be substantially resistant to statin treatment.\",\n \"24.The method of any one of clauses 20 to 22, wherein said biological sample comprises serum, blood, faeces, tissue, a cell, urine and/or saliva of said human.\",\n \"25.The method of any one of clauses 1 to 24, wherein said human is indicated as heterozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising said mutation I474V or E670G, optionally, wherein said human is further indicated as comprising the nucleotide sequence of SEQ ID NO: 28, or said human is indicated as homozygous for a nucleotide sequence encoding the PCSK9 C-terminal domain comprising said mutation I474V or E670G in SEQ ID NO: 1.26.The method of any one of clauses 1 to 25, wherein said human has been diagnosed with at least one condition selected from a lipid disorder, hyperlipoproteinemia, hyperlipidemia, dyslipidemia, hypercholesterolemia, a heart attack, a stroke, coronary heart disease, atherosclerosis, peripheral vascular disease, claudication and high blood pressure.\",\n \"27.The method of any one of clauses 1 to 26, wherein the nucleotide sequence is SEQ ID NO: 29 or 30.28.The method of any one of clauses 1 to 27, wherein said ligand (eg, antibody or antibody fragment) is administered by intravenous or subcutaneous administration and/or is comprised in an injectable preparation.\",\n \"29.A ligand (eg, an antibody or fragment) for use in the method of any one of clauses 1 to 28, wherein the ligand specifically binds the PCSK9.30.A kit comprising the ligand of clause 29 and instructions for carrying out the method of any one of clauses 1 to 28.In an example of any aspect of the invention, the ligand (eg, antibody or fragment, eg, alirocumab, bocovizumab or evolocumab, or an antibody or fragment comprising the variable domains of 316P or 31H4) is administered to the human at a two-weekly dose of from 75 to 150 mg (eg, from 75 to 150 mg administered once or twice over a two-week period).\",\n \"In an example, the ligand is for such administration to the human.\",\n \"Determination of Specific Binding of Ligands of the Invention to PCSK9 Variants Method of SPR Determination of Binding Binding of the antibodies to the PCSK9 variants was carried out by SPR using the ProteOn XPR36™ Array system (BioRad).\",\n \"An anti-human IgG surface (Jackson Labs 109-005-008) was created on a GLC Biosensor chip by primary amine coupling.\",\n \"Test antibodies were captured on this surface as ligands.\",\n \"The PCSK9 variants were used as analytes and passed over the captured antibodies at 256 nM, 64 nM, 16 nM, 4 nM and 1 nM.\",\n \"Binding curves were double referenced using a buffer injection (i.e.\",\n \"0 nM) to remove baseline drift and injection artefacts.\",\n \"Regeneration of the capture surface was with 100 mM phosphoric acid which removed the captured antibody allowing another cycle of capture and binding.\",\n \"The binding sensorgrams generated were analysed using the 1:1 model inherent to the ProteOn XPR36 Array system analysis software.\",\n \"The assay was performed at 25° C. and using 1×HBS-EP (Teknova) as running buffer.\",\n \"Data Three antibodies were tested and the resulting binding data are presented below (Table 3).\",\n \"Antibodies 316P and 31H4 are antibodies disclosed in US20110065902A1 (the sequences of these antibodies and their variable domains are incorporated herein by reference for possible use in the present invention and possible inclusion in claims herein).\",\n \"Antibody 316P comprises heavy chain variable domains derived from recombination of human VH3-23*04 and JH2*01 (with a D), and light chain variable domains derived from recombination of human Vκ4-1*01 and Jκ2*01.Evolocumab comprises a human IGHG2*01 heavy chain and a human IGLC2*01 lambda light chain, a VH derived from recombination of human IGHV1-18*01 and IGHJ6*01 (with a D segment) and a Vλ derived from recombination of human IGLV2-14*01 and IGLJ2*01.TABLE 3 SPR Determination of Ligand Binding Specificity for PCSK9 Variants Variant/Antibody ka (1/Ms) kd (1/s) KD (nM) PCSK9 a 316P 1.37E+06 2.75E−04 0.201 31H4 1.14E+06 6.38E−05 0.056 Evolocumab 1.14E+05 2.62E−05 0.229 PCSK9 a′ 316P 1.50E+06 2.72E−04 0.181 31H4 1.23E+06 6.06E−05 0.049 Evolocumab 1.24E+05 2.29E−05 0.185 PCSK9 c 316P 1.49E+06 2.75E−04 0.184 31H4 1.22E+06 5.69E−05 0.047 Evolocumab 1.20E+05 2.20E−05 0.183 PCSK9 r 316P 1.40E+06 2.76E−04 0.197 31H4 1.15E+06 5.82E−05 0.051 Evolocumab 1.16E+05 2.67E−05 0.230 PCSK9 f 316P 1.39E+06 2.82E−04 0.203 31H4 1.13E+06 5.95E−05 0.053 Evolocumab 1.16E+05 2.66E−05 0.229 PCSK9 p 316P 1.39E+06 2.73E−04 0.196 31H4 1.14E+06 6.12E−05 0.054 Evolocumab 1.14E+05 2.50E−05 0.219 Results The results showed that all antibodies tested bound to PCSK9 variants equally, with any binding variation seen being within experimental error for such a strong affinity interaction.\",\n \"Thus, the invention determines that an antibody with the following profile can specifically bind one or more variants of the invention:— 1.An antibody (eg, 316P or alirocumab) that comprises heavy chain variable domains derived from recombination of human IGHV3-23*04 and IGHJH2*01 (with a D), and light chain variable domains derived from recombination of human IGKV4-1*01 and IGKJ2*01; or 2.An antibody (eg, evolocumab) that comprises human heavy chain variable domains derived from recombination of human IGHV1-18*01 and IGHJ6*01 (with a D segment) and light chain variable domains derived from recombination of human IGLV2-14*01 and IGLJ2*01.Thus, according to the invention, the skilled person is hereby provided with the required determination of specific binding of the ligand to PCSK9 variants.\",\n \"Applications of this determination are set out above in the context of methods and other aspects of the invention.\",\n \"REFERENCES Horton et al, Trends Biochem Sci.\",\n \"2007 February; 32(2):71-7.Epub 2007 Jan. 9, Molecular biology of PCSK9: its role in LDL metabolism.\",\n \"Seidah and Prat, J Mol Med (Berl).\",\n \"2007 July; 85(7):685-96.Epub 2007 Mar.\",\n \"10, The proprotein convertases are potential targets in the treatment of dyslipidemia.\",\n \"Benjannet et al, J Biol Chem.\",\n \"2004 Nov. 19; 279(47):48865-75.Epub 2004 Sep. 9, NARC-1/PCSK9 and its natural mutants: zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol.\",\n \"Lagace et al, J Clin Invest.\",\n \"2006 November; 116(11):2995-3005, Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice.\",\n \"Maxwell et al, Proc Natl Acad Sci USA.\",\n \"2005 Feb. 8; 102(6):2069-74.Epub 2005 Jan. 27, Overexpression of PCSK9 accelerates the degradation of the LDLR in a post-endoplasmic reticulum compartment.\",\n \"Park et al, J Biol Chem.\",\n \"2004 Nov. 26; 279(48):50630-8.Epub 2004 Sep. 22, Post-transcriptional regulation of low density lipoprotein receptor protein by proprotein convertase subtilisin/kexin type 9a in mouse liver.\",\n \"Rashid et al, Proc Natl Acad Sci USA.\",\n \"2005 Apr.\",\n \"12; 102(15):5374-9.Epub 2005 Apr.\",\n \"1, Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9.Kotowski et al, Am J Hum Genet.\",\n \"2006 March; 78(3):410-22.Epub 2006 Jan. 20, A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol.\",\n \"Chen et al, J Am Coll Cardiol.\",\n \"2005 May 17; 45(10): 1611-9.Epub 2005 Apr.\",\n \"21, A common PCSK9 haplotype, encompassing the E670G coding single nucleotide polymorphism, is a novel genetic marker for plasma low-density lipoprotein cholesterol levels and severity of coronary atherosclerosis.\",\n \"Pisciotta et al, Atherosclerosis.\",\n \"2006 June; 186(2):433-40.Epub 2005 Sep. 23, Additive effect of mutations in LDLR and PCSK9 genes on the phenotype of familial hypercholesterolemia.\",\n \"Zhao et al, Am J Hum Genet.\",\n \"2006 September; 79(3):514-23.Epub 2006 Jul.\",\n \"18, Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote.\",\n \"Seidah et al, Proc Natl Acad Sci USA.\",\n \"2003 Feb. 4; 100(3):928-33.Epub 2003 Jan. 27, The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation.\",\n \"TABLE 4 1000 GENOMES PROJECT HUMAN POPULATIONS Below is a summary of the ethnic populations as per the 1000 Genomes Project sequences.\",\n \"Population European ancestry Utah residents (CEPH) with Northern and Western European ancestry (CEU) Toscani in Italia (TSI) British from England and Scotland (GBR) Finnish from Finland (FIN) Iberian populations in Spain (IBS) East Asian ancestry Han Chinese in Beijing, China (CHB) Japanese in Toyko, Japan (JPT) Han Chinese South (CHS) Chinese Dai in Xishuangbanna (CDX) Kinh in Ho Chi Minh City, Vietnam (KHV) Chinese in Denver, Colorado (CHD) (pilot 3 only) West African ancestry Yoruba in Ibadan, Nigeria (YRI) Luhya in Webuye, Kenya (LWK) Gambian in Western Division, The Gambia (GWD) Malawian in Blantyre, Malawi (MAB) West African Population (TBD) Americas African Ancestry in Southwest US (ASW) African American in Jackson, MS (AJM) African Caribbean in Barbados (ACB) Mexican Ancestry in Los Angeles, CA (MXL) Puerto Rican in Puerto Rico (PUR) Colombian in Medellin, Colombia (CLM) Peruvian in Lima, Peru (PEL) South Asian ancestry Ahom in the State of Assam, India Kayadtha in Calcutta, India Reddy in Hyderabad, India Maratha in Bombay, India Punjabi in Lahore, Pakistan TABLE 5 TOIs & Related Diseases, Conditions and Example Ligands Example Disease or Human TOI Condition Example Ligand Il-17a Inflammatory Disease AIN457 Uveitis Ixekizumab Rheumatoid Arthritis Psoriasis Angiotensin II Receptor Type 1 (AT1) Hypertension LCZ696 Neprilysin Hypertension LCZ696 Metabotropic Glutamate Receptor 5 (Mglur5) Fragile X Syndrome AFQ056 Mavoglurant A Histone Deacetylase Cancer, Eg, Multiple LBH589 Myeloma Panobinostat Diacylglycerol acyltransferase-1 (DGAT-1) Familial LCQ908 Chylomicronaemia Pradigastat Syndrome Smoothened (Smo) Basal cell carcinoma LDE225 Solid tumour Myelofibrosis Medulloblastoma Solid tumour Smoothened (Smo) receptor Basal cell carcinoma LEQ506 Solid tumors ALK Non small cell lung LDK378 carcinoma (NSCLC) phosphatidylinositol-3-kinase (PI3K) Cancer, eg, solid tumour, BKM120 mTOR breast cancer, Renal cell AKT carcinoma (RCC), Endometrial cancer, Non- small cell lung cancer (NSCLC), prostate cancer, Glioblastoma multiforme (GBM) CRPC GIST Myelofibrosis mTOR Cancer, eg, solid tumour, BEZ235 PI3K breast cancer, Renal cell AKT carcinoma (RCC), Endometrial cancer, Non- small cell lung cancer (NSCLC), prostate cancer, Glioblastoma multiforme (GBM) CRPC GIST Myelofibrosis PI3Kα Cancer, eg, solid tumour, BYL719 mTOR breast cancer, Renal cell PI3K carcinoma (RCC), AKT Endometrial cancer, Non- small cell lung cancer (NSCLC), prostate cancer, Glioblastoma multiforme (GBM) CRPC GIST Myelofibrosis Mitogen-activated ERK kinase 1 (MEK1) Cancer, eg, solid tumour, MEK162 Mitogen-activated ERK kinase 2 (MEK2) melanoma, pancreatic, colon, lung or thyroid cancer Metastasis protein kinase Acute myeloid leukemia PKC412 protein kinase C (AML) Midostaurin FLT-3 Myelodysplastic syndrome c-KIT (MDS) Aggressive systemic mastocytosis (ASM) ActRIIB Sporadic inclusion body BYM338 myositis (sIBM) bimagrumab CD19 Cancer, eg, CTL019 (formerly CART- Leukaemia, mast 19) cell leukemia, Acute Lymphoblastic Leukemia, Chronic lymphocytic leukemia (CLL) or Hematological tumors 11β-hydroxylase Cushing's syndrome LCI699 BRAF Cancer, eg, melanoma LGX818 Receptor Tyrosine Kinase Cancer, eg, solid TKI258 (formerly CHIR- FGFR tumour 258) Breast Cancer Dovitinib Endometrial cancer Hepatocellular carcinoma Renal cell carcinoma (RCC) Bladder cancer multiple myeloma (MM), hepatocellular carcinoma endometrial cancer DAC enzyme hematologic malignancy LBH589 Multiple myeloma panobinostat Myel\\\\odysplastic syndrome (MDS) Myelofibrosis HSP90 Cancer, eg, Breast AUY922 Cancer, gastric cancer or Non- small cell lung cancer (NSCLC) FGFR Cancer, eg, solid BGJ398 tumour Breast Cancer Endometrial cancer Hepatocellular carcinoma Renal cell carcinoma (RCC) Bladder cancer multiple myeloma (MM), hepatocellular carcinoma endometrial cancer cIAP1 Cancer, eg, solid LCL161 cIAP2 tumour Breast Cancer Endometrial cancer Hepatocellular carcinoma Renal cell carcinoma (RCC) Bladder cancer multiple myeloma (MM), hepatocellular carcinoma endometrial cancer Akt Cancer, eg, Solid GDC-0068 tumour, gastric RG7440 cancer (eg, castration-resistant prostate cancer), prostate cancer, gastroesophageal junction cancer CD22 Hematologic malignancies DCDT2980S Non-Hodgkin's lymphoma RG7593 (eg, relapsed or refractory follicular non-Hodgkin's lymphoma) Diffuse large B-cell lymphoma (eg, relapsed or refractory diffuse large B- cell lymphoma) CD79b Hematologic malignancies DCDS4501A Non-Hodgkin's lymphoma RG7596 (eg, relapsed or refractory follicular non-Hodgkin's lymphoma) Diffuse large B-cell lymphoma (eg, relapsed or refractory diffuse large B- cell lymphoma) endothelin B receptor (ETBR) Melanoma, eg, metastatic DEDN6526A or unresectable melanoma RG7636 HER3 Cancer, eg, metastatic MEHD7945A epithelial tumour, RG7597 metastatic squamous cell carcinoma of the head and neck cancer, metastatic colorectal cancer EGFR Cancer, eg, metastatic MEHD7945A epithelial tumour, RG7597 metastatic squamous cell Necitumumab carcinoma of the head and neck cancer, metastatic colorectal cancer MUC16 Cancer, eg, ovarian cancer DMUC5754A (eg, platinum-resistant RG7458 ovarian cancer) sodium-dependent phosphate transport protein Cancer, eg, metastatic non- DNIB0600A 2b (NaPi2b) squamous non-small cell RG7599 lung cancer, ovarian cancer (eg, platinum-resistant ovarian cancer) PDL1 (programmed death ligand 1) Cancer, eg, solid tumour MPDL3280A metastatic melanoma RG7446 non-small cell lung cancer STEAP1 (six-transmembrane epithelial Cancer, eg, prostate cancer DSTP3086S antigen of the prostate 1) (eg, metastatic castration- RG7450 resistant prostate cancer) Bcl-2 Cancer, eg, leukaemia (eg, GDC-0199 chronic lymphocytic RG7601 leukaemia), non-Hodgkin's lymphoma Checkpoint kinase 1 (ChK1) Cancer, eg, solid tumour, GDC-0425 refractory solid tumour or RG7602 lymphoma GDC-0575 RG7741 mitogen activated protein kinase kinase Cancer, eg, solid tumour, GDC-0973 (MAPKK) melanoma (eg, metastatic RG7421 MEK melanoma) Cobimetinib GDC-0623 RG7420 epidermal growth factor domain-like-7 Cancer, eg, colorectal Parsatuzumab (EGFL7) cancer (eg, metastatic MEGF0444A colorectal cancer), NSCLC RG7414 phosphatidylinositol-3-kinase (PI3K) Cancer, eg, prostate cancer, GDC-0032 renal cell carcinoma, RG7604 endometrial cancer, breast GDC-0084 cancer (eg, HER2-negative RG7666 metastatic breast cancer, Pictilisib metastatic hormone GDC-0941 receptor-positive breast RG7321 cancer), solid tumour mTOR Cancer, eg, prostate cancer, GDC-0980 TORC1 renal cell carcinoma, RG7422 TORC2 endometrial cancer, breast PI3K cancer (eg, HER2-negative metastatic breast cancer, metastatic hormone receptor-positive breast cancer), solid tumour IL17 Autoimmune disease Secukinumab Ankylosing spondylitis; ixekizumab Asthma; Multiple myeloma; Multiple sclerosis; Polymyalgia rheumatica; Psoriasis; Psoriatic arthritis; Rheumatoid arthritis; Uveitis M1 prime segment of membrane IgE Allergic Asthma Quilizumab MEMP1972A RG7449 IFN alpha Autoimmune disease Rontalizumab Systemic lupus erythematosus PCSK9 (proprotein convertase subtilisin/kexin coronary heart disease MPSK3169A type 9) (CHD) or high risk of CHD RG7652 hyperlipidaemia hypercholesterolaemia stroke atherosclerosis a cardiovascular disease or condition a condition associated with elevated LDL Vascular Endothelial Growth Factor-A Diabetic Macular Edema EYLEA ® (VEGF-A) (DME), Aflibercept Placental Growth Factor (PlGF) Branch Retinal Vein AVASTIN ™ Occlusion (BRVO) LUCENTIS ™ Wet age-related macular degeneration (Wet AMD) IL-6 receptor Inflammatory disease, eg, Sarilumab rheumatoid arthritis REGN88 Uveitis (eg, non-infectious uveitis) Ankylosing spondylitis; Cancer PCSK9 (proprotein convertase subtilisin/kexin coronary heart disease Alirocumab type 9) (CHD) or high risk of CHD REGN727 hyperlipidaemia LY3015014 hypercholesterolaemia stroke atherosclerosis a cardiovascular disease or condition a condition associated with elevated LDL NGF Osteoarthritis Fasinumab Pain REGN475 IL-4 receptor alpha Allergic asthma Dupilumab eosinophilic asthma REGN668 IL-13 receptor Atopic dermatitis delta-like ligand-4 (Dll4) Cancer Enoticumab REGN421 angiopoietin-2 (Ang2) Cancer Nesvacumab REGN910 GDF8 Metabolic disorder REGN1033 cancer, obesity, diabetes, LY2495655 arthritis, multiple sclerosis, muscular dystrophy, amyotrophic lateral sclerosis, Parkinson's disease, osteoporosis, osteoarthritis, osteopenia, metabolic syndromes (including, but not limited to diabetes, obesity, nutritional disorders, organ atrophy, chronic obstructive pulmonary disease and anorexia) Disuse muscle atrophy cancer-related cachexia ERBB3 Cancer REGN1400 angiopoietin-1 (Ang1) Cancer, eg, ovarian cancer AMG386 angiopoietin-1 (Ang2) VEGF receptor Cancer Motesanib PDGF receptor NSCLC AMG 706 Stem cell factor receptor Breast cancer Thyroid cancer type 1 insulin-like growth factor receptor Cancer Ganitumab (IGF1R) Breast cancer Linsitinib Pancreatic cancer ASP7487 hepatocyte growth factor (HGF) Cancer Rilotumumab Breast cancer Pancreatic cancer HER3 Cancer AMG 888 ErbB3 Breast cancer U3-1287 Pancreatic cancer IL-17 receptor Inflammatory disease AMG 827 Asthma brodalumab Psoriasis sclerostin Bone-related condition AMG 785 postmenopausal CDP7851 osteoporosis fracture healing glucokinase Diabetes AMG 151 ARRY-403 PCSK9 (proprotein convertase subtilisin/kexin coronary heart disease AMG 145 type 9) (CHD) or high risk of CHD Evolocumab hyperlipidaemia hypercholesterolaemia stroke atherosclerosis a cardiovascular disease or condition a condition associated with elevated LDL VLA 2 Inflammatory bowel SAR339658 Integrin α2β1 disease IL-4 Idiopathic pulmonary SAR156597 IL-13 fibrosis lysophosphatidic acid receptor Systemic sclerosis SAR100842 LPA-1 fibrosis LPA-3 Androgen receptor Cancer, eg, prostate cancer, MDV3100 breast cancer enzalutamide HER1 Cancer, eg, NSCLC Erlotinib EGFR ERBITUX ™ VECTIBIX ™ VEGF receptor 1 Cancer, eg, colorectal ASP4130 VEGF receptor 2 cancer, breast cancer tivozanib VEGF receptor 3 JAK Inflammatory disease, eg, ASP015K JAK1 rheumatoid arthritis Baricitinib JAK2 Diabetic nephropathy CD40 Prevention of organ ASP1240 transplant rejection GnRH Endometriosis ASP1707 Cancer, eg, prostate cancer degarelix PDE9 Lower unirary tract ASP4901 symptoms associated with benign prostatic hyperplasia TNF alpha Inflammatory disease, eg, Certolizumab pegol rheumatoid arthritis, psoriasis, chrohn's disease, IBD Programmed cell death protein 1 Cancer Nivolumab Chronic myelocytic MK-3475 leukemia; Hepatitis C virus infection; Hepatocellular carcinoma; Hodgkins disease; Melanoma; Multiple myeloma; Non- Hodgkin lymphoma; Non- small-cell lung cancer; Renal cell carcinoma; Solid tumor; Stage IV melanoma Hepatocyte growth factor Cancer onartuzumab MET Glioblastoma; Hepatocellular carcinoma; Metastatic colorectal cancer; Metastatic non small cell lung cancer; Metastatic stomach cancer; Non-small-cell lung cancer Angiopoietin ligand-1 Breast tumor; Cancer; trebananib Angiopoietin ligand-2 Colorectal tumor; Fallopian Tek tyrosine kinase receptor tube cancer; Gastrointestinal tumor; Glioblastoma; Hepatocellular carcinoma; Metastatic esophageal cancer; Metastatic gastrointestinal cancer; Metastatic non small cell lung cancer; Metastatic ovary cancer; Metastatic renal cancer; Ovary tumor; Peritoneal tumor; Transitional cell carcinoma CD37 modulator Cancer elotuzumab Lymphocyte function antigen-3 receptor Multiple myeloma SLAM family member 7 IL-2 Multiple sclerosis daclizumab IL-2 receptor alpha EGFR Cancer necitumumab Metastatic non small cell lung cancer; Solid tumor IL-5 Asthma; Eosinophilic reslizumab esophagitis B-lymphocyte cell adhesion molecule Cancer, eg Acute Inotuzumab CD22 lymphoblastic leukemia; inotuzumab ozogamicin Follicle center lymphoma; epratuzumab Non-Hodgkin lymphoma; moxetumomab Systemic lupus moxetumomab pasudotox erythematosus, hairy cell leukaemia IL1 beta Acne vulgaris; gevokizumab Atherosclerosis; Behcets disease; Cardiovascular disease; Dermatomyositis; Insulin dependent diabetes; Multiple myeloma; Osteoarthritis; Paraproteinemia; Polymyositis; Pyoderma gangrenosum; Scleritis; Uveitis CD20 Cancer Ocrelizumab Multiple sclerosis ofatumumab follicular lymphoma (eg, refractory or relapsed) diffuse large B cell lymphoma (eg, relapsed) chronic lymphocytic leukaemia (eg, first line therapy or relapsed) IL-23 Crohns disease; tildrakizumab Inflammatory disease; Psoriasis BAFF Autoimmune disease Belimumab Neutrokine alpha systemic lupus Benlysta ™ erythematosus Tabalumab Multiple myeloma vasculitis IL5 Asthma mepolizumab IL6 Inflammatory disease sirukumab rheumatoid arthritis Lp-PLA2 Atherosclerosis darapladib diabetic macular oedema CCR9 chemokine receptor Inflammatory disease Vercirnon rheumatoid arthritis Crohn's disease DOPA decarboxylase Parkinson's Disease Patrome Her2 Cancer, eg, gastric cancer, Tyverb ™ EGFR breast cancer, head and Tykerb ™ neck squamous cell cancer, lapatinib ADP receptor Cardiovascular disease or Brilinta condition Brilique Thrombosis, eg, arterial thrombosis VEGFR Cancer, eg, Caprelsa EGFR medullary thyroid cancer LABA Respiratory disease or PT003 GFF LAMA condition, eg, COPD Factor Xa thromboembolism apixaban Oxelumab OX40 ligand Asthma Graft-versus-host disease Tremelimumab CTLA-4 Cancer, eg, melanoma Ticilimumab CD152 Autoimmune disease ipilimumab MPDL3280A PD-L1 Cancer, eg, solid tumour, MEDI4736 kidney cancer, lung cancer, melanoma, NSCLC, multiple myeloma Autoimmune disease Nivolumab PD-1 Cancer, eg, solid tumour, AMP-514 kidney cancer, lung cancer, AMP-224 melanoma, NSCLC, multiple myeloma Autoimmune disease LIGHT TNFSF14 CD40 ligand JAK Inflammatory disease, eg, tofacitinib rheumatoid arthritis, psoriasis, chrohn's disease, IBD, ulcerative colitis, Psoriatic Arthritis Nerve Growth Factor Pain tanezumab Osteoarthritis pain Her1 receptor Cancer, eg, Non-Small Cell dacomitinib Her2 receptor Lung Cancer Her4 receptor c-MET Cancer, eg, Non-Small Cell crizotinib ALK Lung Cancer Programmed cell death 1 receptor Cancer, eg, renal cell Nivolumab carcinoma SLAMF7 Cancer, eg, multiple Elotuzumab CD319 myeloma CD30 Cancer, eg, Hodgkin Brentuximab lymphoma, systemic Brentuximab vedotin anaplastic large cell lymphoma, T-cell lymphoma GPR40 Diabetes, eg, diabetes Fasiglifam DPP-4 mellitus trelagliptin VEFGR-1 receptor Cancer, eg, non-squamous Motesanib VEFGR-2 receptor non-small cell lung cancer Motesanib diphosphate VEFGR-3 receptor PDGFR cKit amyloid ß Alzheimer's disease Solanezumab TNF alpha Inflammatory disease, eg, SIMPONI ™ rheumatoid arthritis, HUMIRA ™ psoriasis, chrohn's disease, REMICADE ™ IBD, ulcerative colitis, ENBREL ™ Psoriatic Arthritis Adalimumab IL-21 Autoimmune disease or Agonist or antagonist condition antibody specific for Inflammatory disease or human IL-21 condition NNC0114-0005 Rheumatoid arthritis NNC0114-0006 Crohn's disease NN8828 IBD ATR-107 Ulcerative colitis Said or an anti-IL-21 Systemic lupus antibody in combination erythematosus (SLE) with an agent selected from Graft versus host disease the group consisting of Cancer ipilimumab (eg, to treat Metastatic melanoma melanoma), an anti-PD1 Renal cell carcinoma antibody (eg, to treat solid Melanoma tumours), sunitinib (eg, to Solid tumours treat renal cell carcinoma), Acute myeloid leukaemia rituximab (eg, to treat Non- Non-Hodgkin's lymphoma Hodgkin's lymphoma), Ovarian cancer sorafenib (eg, to treat renal Colorectal cancer cell carcinoma), doxorubicin (eg, to treat ovarian cancer) and cetuximab (eg, to treat colorectal cancer).\",\n \"TABLE 6 PCSK9 SEQUENCES SEQ ID FORM/ALLELE VERSION SEQUENCE NO: AMINO ACID SEQUENCES Italics = signal sequence 1-30 Courier = pro peptide 31-152 lower case = catalytic domain 153-449 UPPER CASE = C-terminal domain 450-692 Underlined = residues changed from allele a in other sequences (aa residue number shown) a Pro-Form with 46 53 1 Signal Sequence MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELAILKLPM VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylidtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllpiaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtigtigtnfgrcvdlfapgedllgassdcstcfvsqsgtsqaaahvagiaammisaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPCIANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ a Pro-Form QEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP 2 WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryadeyqppdggslvevylidtslqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqivqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtigtigtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrllhfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ a Mature form sipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg 3 thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvtvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgedllgassdcstcfvsqsgtsqaaahvaglaammlsaepeltlaelrqrllhfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ f Pro-Form with 46 53 Signal Sequence MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP 4 WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ f Pro-Form QEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP 5 WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnlerltppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrsirvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgedllgassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ f, p, aj Mature form sipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg 6 thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ c Pro-Form with 46 53 7 MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvincqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqriaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammisaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEGAVTAVAICCRSRHLAQASQELQ c Pro-Form QEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP 8 WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnlerltppryradeyqppdggslvevyiidtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvinaacqriaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtigtigtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEGAVTAVAICCRSRHLAQASQELQ c, q Mature form sipwnleritppryradeyqppdggslvevylidtsiqsdhrelegrvmvtdfenvpeedgtrfhrqaskcdshg 9 thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEGAVTAVAICCRSRHLAQASQELQ r Pro-Form with 46 53 10 Signal Sequence MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtigtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEGAVTAVAICCRSRHLAQASQELQ r Pro-Form QEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP 11 WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvaglaammlsaepeltlaelrgrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEGAVTAVAICCRSRHLAQASQELQ r Mature form sipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg 12 thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvaglaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEGAVTAVAICCRSRHLAQASQELQ p Pro-Form with 46 53 13 Signal Sequence MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLVEAPEHGTTATFHRCAKDP WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvaglaammlsaepeltlaelrqrflhfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ p Pro-Form QEDEDGDYEELVLALRSEEDGLVEAPEHGTTATFHRCAKDP 14 WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPM VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ m Pro-Form with 46 53 15 Signal Sequence MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvatlppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ m Pro-Form QEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP 16 WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvatlppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ m Mature form sipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg 17 thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvatlppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ e Pro-Form with 46 53 18 Signal Sequence MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtigtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dviseawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ e Pro-Form QEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP 19 WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dviseawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ e Mature form sipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg 20 thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dviseawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ h Pro-Form with 46 53 21 Signal Sequence MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtigtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvatlppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPPEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ h Pro-Form QEDEDGDYEELVLALRSEEDGLAEAPEHGTTATFHRCAKDP 22 WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvatlppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPPEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ h Mature form sipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg 23 thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvatlppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPPEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ aj Pro-Form with 46 53 24 Signal Sequence MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALLSEEDGLAEAPEHGTTATFHRCAKDP WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtigtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ aj Pro-Form QEDEDGDYEELVLALLSEEDGLAEAPEHGTTATFHRCAKDP 25 WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAVARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEEAVTAVAICCRSRHLAQASQELQ q Pro-Form with 46 53 26 Signal Sequence MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLVEAPEHGTTATFHRCAKDP WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtigtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEGAVTAVAICCRSRHLAQASQELQ q Pro-Form QEDEDGDYEELVLALRSEEDGLVEAPEHGTTATFHRCAKDP 27 WRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLPGFLVKMSGDLLELALKLPH VDYIEEDSSVFAQsipwnleritppryradeyqppdggslvevylldtsiqsdhreiegrvmvtdfenvpeedgtrfhrqaskcdshg thlagvvsgrdagvakgasmrslrvlncqgkgtvsgtliglefirksqlvqpvgplvvllplaggysrvlnaacqrlaragvvlvtaagnfrddacly spasapevitvgatnaqdqpvtlgtlgtnfgrcvdlfapgediigassdcstcfvsqsgtsqaaahvagiaammlsaepeltlaelrqrlihfsak 425 443 474 dvineawfpedqrvltpnlvaalppsthGAGWQLFCRTVWSAHSGPTRMATAIARCAPDEELLSCSSFSRSGKRRGERM EAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAPPAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGT 619620 HKPPVLRPRGQPNQCVGHREASIHASCCHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAY 670 AVDNTCVVRSRDVSTTGSTSEGAVTAVAICCRSRHLAQASQELQ NUCLEOTIDE SEQUENCES Italics = nucleotide sequence encoding signal sequence (nucleotides 1-90) Courier = nucleotide sequence encoding pro peptide (nucleotides 91-456) lower case = nucleotide sequence encoding catalytic domain (nucleotides 457-1346) UPPER CASE = nucleotide sequence encoding C-terminal domain (nucleotides 1347-2076) a ATGGGCACCGTCAGCTCCAGGCGGTCCTGGTGGCCGCTGCCACTGCTGCTGCTGCTGCTGCTGCTCCTGGGTC 28 R46L CGT to CTT CCGCGGGCGCCCGTGCGCAGGAGGACGAGGACGGCGACTACGAGGAGCTGGTGCTAGCCTTGCGTTCCG A53V GCC to GTC AGGAGGACGGCCTGGCCGAAGCACCCGAGCACGGAACCACAGCCACCTTCCACCGCTGCGCCAAGGAT CCGTGGAGGTTGCCTGGCACCTACGTGGTGGTGCTGAAGGAGGAGACCCACCTCTCGCAGTCAGAGCG CACTGCCCGCCGCCTGCAGGCCCAGGCTGCCCGCCGGGGATACCTCACCAAGATCCTGCATGTCTTCC ATGGCCTTCTTCCTGGCTTCCTGGTGAAGATGAGTGGCGACCTGCTGGAGCTGGCCTTGAAGTTGCCC CATGTCGACTACATCGAGGAGGACTCCTCTGTCTTTGCCCAGagcatcccgtggaacctggagcggattacccctcca cggtaccgggcggatgaataccagccccccgacggaggcagcctggtggaggtgtatctcctagacaccagcatacagagtgaccaccgggaa atcgagggcagggtcatggtcaccgacttcgagaatgtgcccgaggaggacgggacccgcttccacagacaggccagcaagtgtgacagtcat ggcacccacctggcaggggtggtcagcggccgggatgccggcgtggccaagggtgccagcatgcgcagcctgcgcgtgctcaactgccaaggg aagggcacggttagcggcaccctcataggcctggagtttattcggaaaagccagctggtccagcctgtggggccactggtggtgctgctgcccct ggcgggtgggtacagccgcgtcctcaacgccgcctgccagcgcctggcgagggctggggtcgtgctggtcaccgctgccggcaacttccgggac gatgcctgcctctactccccagcctcagctcccgaggtcatcacagttggggccaccaatgcccaagaccagccggtgaccctggggactttggg gaccaactttggccgctgtgtggacctctttgccccaggggaggacatcattggtgcctccagcgactgcagcacctgctttgtgtcacagagtgg gacatcacaggctgctgcccacgtggctggcattgcagccatgatgctgctgccgagccggagctaccctggccgagttgaggcagagactg N425S AAT to AGT A443T GCC to ACC atccacttctctgccaaagatgtcatcaatgaggcctggttccctgaggaccagcgggtactgacccccaacctggtggccgccctgccccccag cacccatGGGGCAGGTTGGCAGCTGTTTTGCAGGACTGTATGGTCAGCACACTCGGGGCCTACACGGATGGCC I474V ATC to GTC ACAGCCATCGCCCGCTGCGCCCCAGATGAGGAGCTGCTGAGCTGCTCCAGTTTCTCCAGGAGTGGGAAGCGG CGGGGCGAGCGCATGGAGGCCCAAGGGGGCAAGCTGGTCTGCCGGGCCCACAACGCTTTTGGGGGTGAGGG TGTCTACGCCATTGCCAGGTGCTGCCTGCTACCCCAGGCCAACTGCAGCGTCCACACAGCTCCACCAGCTGAG GCCAGCATGGGGACCCGTGTCCACTGCCACCAACAGGGCCACGTCCTCACAGGCTGCAGCTCCCACTGGGAG GTGGAGGACCTTGGCACCCACAAGCCGCCTGTGCTGAGGCCACGAGGTCAGCCCAACCAGTGCGTGGGCCAC AGGGAGGCCAGCATCCACGCTTCCTGCTGCCATGCCCCAGGTCTGGAATGCAAAGTCAAGGAGCATGGAA Q619P CAG to CCG E620G GAG to GGG TCCCGGCCCCTCAGGAGCAGGTGACCGTGGCCTGCGAGGAGGGCTGGACCCTGACTGGCTGCAGTGCCCTCC CTGGGACCTCCCACGTCCTGGGGGCCTACGCCGTAGACAACACGTGTGTAGTCAGGAGCCGGGACGTCAGCA E670G GAG to GGG CTACAGGCAGCACCAGCGAAGAGGCCGTGACAGCCGTTGCCATCTGCTGCCGGAGCCGGCACCTGGCGCAGG CCTCCCAGGAGCTCCAGTGAC f ATGGGCACCGTCAGCTCCAGGCGGTCCTGGTGGCCGCTGCCACTGCTGCTGCTGCTGCTGCTGCTCCTGGGTC 29 R46L CGT to CTT CCGCGGGCGCCCGTGCGCAGGAGGACGAGGACGGCGACTACGAGGAGCTGGTGCTAGCCTTGCGTTCCG A53V GCC to GTC AGGAGGACGGCCTGGCCGAAGCACCCGAGCACGGAACCACAGCCACCTTCCACCGCTGCGCCAAGGAT CCGTGGAGGTTGCCTGGCACCTACGTGGTGGTGCTGAAGGAGGAGACCCACCTCTCGCAGTCAGAGCG CACTGCCCGCCGCCTGCAGGCCCAGGCTGCCCGCCGGGGATACCTCACCAAGATCCTGCATGTCTTCC ATGGCCTTCTTCCTGGCTTCCTGGTGAAGATGAGTGGCGACCTGCTGGAGCTGGCCTTGAAGTTGCCC CATGTCGACTACATCGAGGAGGACTCCTCTGTCTTTGCCCAGagcatcccgtggaacctggagcggattacccctcca cggtaccgggcggatgaataccagccccccgacggaggcagcctggtggaggtgtatctcctagacaccagcatacagagtgaccaccgggaa atcgagggcagggtcatggtcaccgacttcgagaatgtgcccgaggaggacgggacccgcttccacagacaggccagcaagtgtgacagtcat ggcacccacctggcaggggtggtcagcggccgggatgccggcgtggccaagggtgccagcatgcgcagcctgcgcgtgctcaactgccaaggg aagggcacggttagcggcaccctcataggcctggagtttattcggaaaagccagctggtccagcctgtggggccactggtggtgctgctgcccct ggcgggtgggtacagccgcgtcctcaacgccgcctgccagcgcctggcgagggctggggtcgtgctggtcaccgctgccggcaacttccgggac gatgcctgcctctactccccagcctcagctcccgaggtcatcacagttggggccaccaatgcccaagaccagccggtgaccctggggactttggg gaccaactttggccgctgtgtggacctctttgccccaggggaggacatcattggtgcctccagcgactgcagcacctgctttgtgtcacagagtgg gacatcacaggctgctgcccacgtggctggcattgcagccatgatgctgctgccgagccggagctaccctggccgagttgaggcagagactg N425S AAT to AGT A443T GCC to ACC atccacttctctgccaaagatgtcatcaatgaggcctggttccctgaggaccagcgggtactgacccccaacctggtggccgccctgccccccag cacccatGGGGCAGGTTGGCAGCTGTTTTGCAGGACTGTATGGTCAGCACACTCGGGGCCTACACGGATGGCC I474V ATC to GTC ACAGCCGTCGCCCGCTGCGCCCCAGATGAGGAGCTGCTGAGCTGCTCCAGTTTCTCCAGGAGTGGGAAGCGG CGGGGCGAGCGCATGGAGGCCCAAGGGGGCAAGCTGGTCTGCCGGGCCCACAACGCTTTTGGGGGTGAGGG TGTCTACGCCATTGCCAGGTGCTGCCTGCTACCCCAGGCCAACTGCAGCGTCCACACAGCTCCACCAGCTGAG GCCAGCATGGGGACCCGTGTCCACTGCCACCAACAGGGCCACGTCCTCACAGGCTGCAGCTCCCACTGGGAG GTGGAGGACCTTGGCACCCACAAGCCGCCTGTGCTGAGGCCACGAGGTCAGCCCAACCAGTGCGTGGGCCAC AGGGAGGCCAGCATCCACGCTTCCTGCTGCCATGCCCCAGGTCTGGAATGCAAAGTCAAGGAGCATGGAA Q619P CAG to CCG E620G GAG to GGG TCCCGGCCCCTCAGGAGCAGGTGACCGTGGCCTGCGAGGAGGGCTGGACCCTGACTGGCTGCAGTGCCCTCC CTGGGACCTCCCACGTCCTGGGGGCCTACGCCGTAGACAACACGTGTGTAGTCAGGAGCCGGGACGTCAGCA E670G GAG to GGG CTACAGGCAGCACCAGCGAAGAGGCCGTGACAGCCGTTGCCATCTGCTGCCGGAGCCGGCACCTGGCGCAGG CCTCCCAGGAGCTCCAGTGAC c ATGGGCACCGTCAGCTCCAGGCGGTCCTGGTGGCCGCTGCCACTGCTGCTGCTGCTGCTGCTGCTCCTGGGTC 30 R46L CGT to CTT CCGCGGGCGCCCGTGCGCAGGAGGACGAGGACGGCGACTACGAGGAGCTGGTGCTAGCCTTGCGTTCCG A53V GCC to GTC AGGAGGACGGCCTGGCCGAAGCACCCGAGCACGGAACCACAGCCACCTTCCACCGCTGCGCCAAGGAT CCGTGGAGGTTGCCTGGCACCTACGTGGTGGTGCTGAAGGAGGAGACCCACCTCTCGCAGTCAGAGCG CACTGCCCGCCGCCTGCAGGCCCAGGCTGCCCGCCGGGGATACCTCACCAAGATCCTGCATGTCTTCC ATGGCCTTCTTCCTGGCTTCCTGGTGAAGATGAGTGGCGACCTGCTGGAGCTGGCCTTGAAGTTGCCC CATGTCGACTACATCGAGGAGGACTCCTCTGTCTTTGCCCAGagcatcccgtggaacctggagcggattacccctcca cggtaccgggcggatgaataccagccccccgacggaggcagcctggtggaggtgtatctcctagacaccagcatacagagtgaccaccgggaa atcgagggcagggtcatggtcaccgacttcgagaatgtgcccgaggaggacgggacccgcttccacagacaggccagcaagtgtgacagtcat ggcacccacctggcaggggtggtcagcggccgggatgccggcgtggccaagggtgccagcatgcgcagcctgcgcgtgctcaactgccaaggg aagggcacggttagcggcaccctcataggcctggagtttattcggaaaagccagctggtccagcctgtggggccactggtggtgctgctgcccct ggcgggtgggtacagccgcgtcctcaacgccgcctgccagcgcctggcgagggctggggtcgtgctggtcaccgctgccggcaacttccgggac gatgcctgcctctactccccagcctcagctcccgaggtcatcacagttggggccaccaatgcccaagaccagccggtgaccctggggactttggg gaccaactttggccgctgtgtggacctctttgccccaggggaggacatcattggtgcctccagcgactgcagcacctgctttgtgtcacagagtgg gacatcacaggctgctgcccacgtggctggcattgcagccatgatgctgctgccgagccggagctaccctggccgagttgaggcagagactg N425S AAT to AGT A443T GCC to ACC atccacttctctgccaaagatgtcatcaatgaggcctggttccctgaggaccagcgggtactgacccccaacctggtggccgccctgccccccag cacccatGGGGCAGGTTGGCAGCTGTTTTGCAGGACTGTATGGTCAGCACACTCGGGGCCTACACGGATGGCC I474V ATC to GTC ACAGCCATCGCCCGCTGCGCCCCAGATGAGGAGCTGCTGAGCTGCTCCAGTTTCTCCAGGAGTGGGAAGCGG CGGGGCGAGCGCATGGAGGCCCAAGGGGGCAAGCTGGTCTGCCGGGCCCACAACGCTTTTGGGGGTGAGGG TGTCTACGCCATTGCCAGGTGCTGCCTGCTACCCCAGGCCAACTGCAGCGTCCACACAGCTCCACCAGCTGAG GCCAGCATGGGGACCCGTGTCCACTGCCACCAACAGGGCCACGTCCTCACAGGCTGCAGCTCCCACTGGGAG GTGGAGGACCTTGGCACCCACAAGCCGCCTGTGCTGAGGCCACGAGGTCAGCCCAACCAGTGCGTGGGCCAC AGGGAGGCCAGCATCCACGCTTCCTGCTGCCATGCCCCAGGTCTGGAATGCAAAGTCAAGGAGCATGGAA Q619P CAG to CCG E620G GAG to GGG TCCCGGCCCCTCAGGAGCAGGTGACCGTGGCCTGCGAGGAGGGCTGGACCCTGACTGGCTGCAGTGCCCTCC CTGGGACCTCCCACGTCCTGGGGGCCTACGCCGTAGACAACACGTGTGTAGTCAGGAGCCGGGACGTCAGCA E670G GAG to GGG CTACAGGCAGCACCAGCGAAGGGGCCGTGACAGCCGTTGCCATCTGCTGCCGGAGCCGGCACCTGGCGCAGG CCTCCCAGGAGCTCCAGTGAC r ATGGGCACCGTCAGCTCCAGGCGGTCCTGGTGGCCGCTGCCACTGCTGCTGCTGCTGCTGCTGCTCCTGGGTC 31 R46L CGT to CTT CCGCGGGCGCCCGTGCGCAGGAGGACGAGGACGGCGACTACGAGGAGCTGGTGCTAGCCTTGCGTTCCG A53V GCC to GTC AGGAGGACGGCCTGGCCGAAGCACCCGAGCACGGAACCACAGCCACCTTCCACCGCTGCGCCAAGGAT CCGTGGAGGTTGCCTGGCACCTACGTGGTGGTGCTGAAGGAGGAGACCCACCTCTCGCAGTCAGAGCG CACTGCCCGCCGCCTGCAGGCCCAGGCTGCCCGCCGGGGATACCTCACCAAGATCCTGCATGTCTTCC ATGGCCTTCTTCCTGGCTTCCTGGTGAAGATGAGTGGCGACCTGCTGGAGCTGGCCTTGAAGTTGCCC CATGTCGACTACATCGAGGAGGACTCCTCTGTCTTTGCCCAGagcatcccgtggaacctggagcggattacccctcca cggtaccgggcggatgaataccagccccccgacggaggcagcctggtggaggtgtatctcctagacaccagcatacagagtgaccaccgggaa atcgagggcagggtcatggtcaccgacttcgagaatgtgcccgaggaggacgggacccgcttccacagacaggccagcaagtgtgacagtcat ggcacccacctggcaggggtggtcagcggccgggatgccggcgtggccaagggtgccagcatgcgcagcctgcgcgtgctcaactgccaaggg aagggcacggttagcggcaccctcataggcctggagtttattcggaaaagccagctggtccagcctgtggggccactggtggtgctgctgcccct ggcgggtgggtacagccgcgtcctcaacgccgcctgccagcgcctggcgagggctggggtcgtgctggtcaccgctgccggcaacttccgggac gatgcctgcctctactccccagcctcagctcccgaggtcatcacagttggggccaccaatgcccaagaccagccggtgaccctggggactttggg gaccaactttggccgctgtgtggacctctttgccccaggggaggacatcattggtgcctccagcgactgcagcacctgctttgtgtcacagagtgg gacatcacaggctgctgcccacgtggctggcattgcagccatgatgctgctgccgagccggagctaccctggccgagttgaggcagagactg N425S AAT to AGT A443T GCC to ACC atccacttctctgccaaagatgtcatcaatgaggcctggttccctgaggaccagcgggtactgacccccaacctggtggccgccctgccccccag cacccatGGGGCAGGTTGGCAGCTGTTTTGCAGGACTGTATGGTCAGCACACTCGGGGCCTACACGGATGGCC I474V ATC to GTC ACAGCCGTCGCCCGCTGCGCCCCAGATGAGGAGCTGCTGAGCTGCTCCAGTTTCTCCAGGAGTGGGAAGCGG CGGGGCGAGCGCATGGAGGCCCAAGGGGGCAAGCTGGTCTGCCGGGCCCACAACGCTTTTGGGGGTGAGGG TGTCTACGCCATTGCCAGGTGCTGCCTGCTACCCCAGGCCAACTGCAGCGTCCACACAGCTCCACCAGCTGAG GCCAGCATGGGGACCCGTGTCCACTGCCACCAACAGGGCCACGTCCTCACAGGCTGCAGCTCCCACTGGGAG GTGGAGGACCTTGGCACCCACAAGCCGCCTGTGCTGAGGCCACGAGGTCAGCCCAACCAGTGCGTGGGCCAC AGGGAGGCCAGCATCCACGCTTCCTGCTGCCATGCCCCAGGTCTGGAATGCAAAGTCAAGGAGCATGGAA Q619P CAG to CCG E620G GAG to GGG TCCCGGCCCCTCAGGAGCAGGTGACCGTGGCCTGCGAGGAGGGCTGGACCCTGACTGGCTGCAGTGCCCTCC CTGGGACCTCCCACGTCCTGGGGGCCTACGCCGTAGACAACACGTGTGTAGTCAGGAGCCGGGACGTCAGCA E670G GAG to GGG CTACAGGCAGCACCAGCGAAGGGGCCGTGACAGCCGTTGCCATCTGCTGCCGGAGCCGGCACCTGGCGCAGG CCTCCCAGGAGCTCCAGTGAC p ATGGGCACCGTCAGCTCCAGGCGGTCCTGGTGGCCGCTGCCACTGCTGCTGCTGCTGCTGCTGCTCCTGGGTC 32 R46L CGT to CTT CCGCGGGCGCCCGTGCGCAGGAGGACGAGGACGGCGACTACGAGGAGCTGGTGCTAGCCTTGCGTTCCG A53V GCC to GTC AGGAGGACGGCCTGGTCGAAGCACCCGAGCACGGAACCACAGCCACCTTCCACCGCTGCGCCAAGGAT CCGTGGAGGTTGCCTGGCACCTACGTGGTGGTGCTGAAGGAGGAGACCCACCTCTCGCAGTCAGAGCG CACTGCCCGCCGCCTGCAGGCCCAGGCTGCCCGCCGGGGATACCTCACCAAGATCCTGCATGTCTTCC ATGGCCTTCTTCCTGGCTTCCTGGTGAAGATGAGTGGCGACCTGCTGGAGCTGGCCTTGAAGTTGCCC CATGTCGACTACATCGAGGAGGACTCCTCTGTCTTTGCCCAGagcatcccgtggaacctggagcggattacccctcca cggtaccgggcggatgaataccagccccccgacggaggcagcctggtggaggtgtatctcctagacaccagcatacagagtgaccaccgggaa atcgagggcagggtcatggtcaccgacttcgagaatgtgcccgaggaggacgggacccgcttccacagacaggccagcaagtgtgacagtcat ggcacccacctggcaggggtggtcagcggccgggatgccggcgtggccaagggtgccagcatgcgcagcctgcgcgtgctcaactgccaaggg aagggcacggttagcggcaccctcataggcctggagtttattcggaaaagccagctggtccagcctgtggggccactggtggtgctgctgcccct ggcgggtgggtacagccgcgtcctcaacgccgcctgccagcgcctggcgagggctggggtcgtgctggtcaccgctgccggcaacttccgggac gatgcctgcctctactccccagcctcagctcccgaggtcatcacagttggggccaccaatgcccaagaccagccggtgaccctggggactttggg gaccaactttggccgctgtgtggacctctttgccccaggggaggacatcattggtgcctccagcgactgcagcacctgctttgtgtcacagagtgg gacatcacaggctgctgcccacgtggctggcattgcagccatgatgctgctgccgagccggagctaccctggccgagttgaggcagagactg N425S AAT to AGT A443T GCC to ACC atccacttctctgccaaagatgtcatcaatgaggcctggttccctgaggaccagcgggtactgacccccaacctggtggccgccctgccccccag cacccatGGGGCAGGTTGGCAGCTGTTTTGCAGGACTGTATGGTCAGCACACTCGGGGCCTACACGGATGGCC I474V ATC to GTC ACAGCCGTCGCCCGCTGCGCCCCAGATGAGGAGCTGCTGAGCTGCTCCAGTTTCTCCAGGAGTGGGAAGCGG CGGGGCGAGCGCATGGAGGCCCAAGGGGGCAAGCTGGTCTGCCGGGCCCACAACGCTTTTGGGGGTGAGGG TGTCTACGCCATTGCCAGGTGCTGCCTGCTACCCCAGGCCAACTGCAGCGTCCACACAGCTCCACCAGCTGAG GCCAGCATGGGGACCCGTGTCCACTGCCACCAACAGGGCCACGTCCTCACAGGCTGCAGCTCCCACTGGGAG GTGGAGGACCTTGGCACCCACAAGCCGCCTGTGCTGAGGCCACGAGGTCAGCCCAACCAGTGCGTGGGCCAC AGGGAGGCCAGCATCCACGCTTCCTGCTGCCATGCCCCAGGTCTGGAATGCAAAGTCAAGGAGCATGGAA Q619P CAG to CCG E620G GAG to GGG TCCCGGCCCCTCAGGAGCAGGTGACCGTGGCCTGCGAGGAGGGCTGGACCCTGACTGGCTGCAGTGCCCTCC CTGGGACCTCCCACGTCCTGGGGGCCTACGCCGTAGACAACACGTGTGTAGTCAGGAGCCGGGACGTCAGCA E670G GAG to GGG CTACAGGCAGCACCAGCGAAGAGGCCGTGACAGCCGTTGCCATCTGCTGCCGGAGCCGGCACCTGGCGCAGG CCTCCCAGGAGCTCCAGTGAC m ATGGGCACCGTCAGCTCCAGGCGGTCCTGGTGGCCGCTGCCACTGCTGCTGCTGCTGCTGCTGCTCCTGGGTC 33 R46L CGT to CTT CCGCGGGCGCCCGTGCGCAGGAGGACGAGGACGGCGACTACGAGGAGCTGGTGCTAGCCTTGCGTTCCG A53V GCC to GTC AGGAGGACGGCCTGGCCGAAGCACCCGAGCACGGAACCACAGCCACCTTCCACCGCTGCGCCAAGGAT CCGTGGAGGTTGCCTGGCACCTACGTGGTGGTGCTGAAGGAGGAGACCCACCTCTCGCAGTCAGAGCG CACTGCCCGCCGCCTGCAGGCCCAGGCTGCCCGCCGGGGATACCTCACCAAGATCCTGCATGTCTTCC ATGGCCTTCTTCCTGGCTTCCTGGTGAAGATGAGTGGCGACCTGCTGGAGCTGGCCTTGAAGTTGCCC CATGTCGACTACATCGAGGAGGACTCCTCTGTCTTTGCCCAGagcatcccgtggaacctggagcggattacccctcca cggtaccgggcggatgaataccagccccccgacggaggcagcctggtggaggtgtatctcctagacaccagcatacagagtgaccaccgggaa atcgagggcagggtcatggtcaccgacttcgagaatgtgcccgaggaggacgggacccgcttccacagacaggccagcaagtgtgacagtcat ggcacccacctggcaggggtggtcagcggccgggatgccggcgtggccaagggtgccagcatgcgcagcctgcgcgtgctcaactgccaaggg aagggcacggttagcggcaccctcataggcctggagtttattcggaaaagccagctggtccagcctgtggggccactggtggtgctgctgcccct ggcgggtgggtacagccgcgtcctcaacgccgcctgccagcgcctggcgagggctggggtcgtgctggtcaccgctgccggcaacttccgggac gatgcctgcctctactccccagcctcagctcccgaggtcatcacagttggggccaccaatgcccaagaccagccggtgaccctggggactttggg gaccaactttggccgctgtgtggacctctttgccccaggggaggacatcattggtgcctccagcgactgcagcacctgctttgtgtcacagagtgg gacatcacaggctgctgcccacgtggctggcattgcagccatgatgctgctgccgagccggagctaccctggccgagttgaggcagagactg N425S AAT to AGT A443T GCC to ACC atccacttctctgccaaagatgtcatcaatgaggcctggttccctgaggaccagcgggtactgacccccaacctggtggccaccctgccccccag cacccatGGGGCAGGTTGGCAGCTGTTTTGCAGGACTGTATGGTCAGCACACTCGGGGCCTACACGGATGGCC I474V ATC to GTC ACAGCCATCGCCCGCTGCGCCCCAGATGAGGAGCTGCTGAGCTGCTCCAGTTTCTCCAGGAGTGGGAAGCGG CGGGGCGAGCGCATGGAGGCCCAAGGGGGCAAGCTGGTCTGCCGGGCCCACAACGCTTTTGGGGGTGAGGG TGTCTACGCCATTGCCAGGTGCTGCCTGCTACCCCAGGCCAACTGCAGCGTCCACACAGCTCCACCAGCTGAG GCCAGCATGGGGACCCGTGTCCACTGCCACCAACAGGGCCACGTCCTCACAGGCTGCAGCTCCCACTGGGAG GTGGAGGACCTTGGCACCCACAAGCCGCCTGTGCTGAGGCCACGAGGTCAGCCCAACCAGTGCGTGGGCCAC AGGGAGGCCAGCATCCACGCTTCCTGCTGCCATGCCCCAGGTCTGGAATGCAAAGTCAAGGAGCATGGAA Q619P CAG to CCG E620G GAG to GGG TCCCGGCCCCTCAGGAGCAGGTGACCGTGGCCTGCGAGGAGGGCTGGACCCTGACTGGCTGCAGTGCCCTCC CTGGGACCTCCCACGTCCTGGGGGCCTACGCCGTAGACAACACGTGTGTAGTCAGGAGCCGGGACGTCAGCA E670G GAG to GGG CTACAGGCAGCACCAGCGAAGAGGCCGTGACAGCCGTTGCCATCTGCTGCCGGAGCCGGCACCTGGCGCAGG CCTCCCAGGAGCTCCAGTGAC e ATGGGCACCGTCAGCTCCAGGCGGTCCTGGTGGCCGCTGCCACTGCTGCTGCTGCTGCTGCTGCTCCTGGGTC 34 R46L CGT to CTT CCGCGGGCGCCCGTGCGCAGGAGGACGAGGACGGCGACTACGAGGAGCTGGTGCTAGCCTTGCGTTCCG A53V GCC to GTC AGGAGGACGGCCTGGCCGAAGCACCCGAGCACGGAACCACAGCCACCTTCCACCGCTGCGCCAAGGAT CCGTGGAGGTTGCCTGGCACCTACGTGGTGGTGCTGAAGGAGGAGACCCACCTCTCGCAGTCAGAGCG CACTGCCCGCCGCCTGCAGGCCCAGGCTGCCCGCCGGGGATACCTCACCAAGATCCTGCATGTCTTCC ATGGCCTTCTTCCTGGCTTCCTGGTGAAGATGAGTGGCGACCTGCTGGAGCTGGCCTTGAAGTTGCCC CATGTCGACTACATCGAGGAGGACTCCTCTGTCTTTGCCCAGagcatcccgtggaacctggagcggattacccctcca cggtaccgggcggatgaataccagccccccgacggaggcagcctggtggaggtgtatctcctagacaccagcatacagagtgaccaccgggaa atcgagggcagggtcatggtcaccgacttcgagaatgtgcccgaggaggacgggacccgcttccacagacaggccagcaagtgtgacagtcat ggcacccacctggcaggggtggtcagcggccgggatgccggcgtggccaagggtgccagcatgcgcagcctgcgcgtgctcaactgccaaggg aagggcacggttagcggcaccctcataggcctggagtttattcggaaaagccagctggtccagcctgtggggccactggtggtgctgctgcccct ggcgggtgggtacagccgcgtcctcaacgccgcctgccagcgcctggcgagggctggggtcgtgctggtcaccgctgccggcaacttccgggac gatgcctgcctctactccccagcctcagctcccgaggtcatcacagttggggccaccaatgcccaagaccagccggtgaccctggggactttggg gaccaactttggccgctgtgtggacctctttgccccaggggaggacatcattggtgcctccagcgactgcagcacctgctttgtgtcacagagtgg gacatcacaggctgctgcccacgtggctggcattgcagccatgatgctgctgccgagccggagctaccctggccgagttgaggcagagactg N425S AAT to AGT A443T GCC to ACC atccacttctctgccaaagatgtcatcagtgaggcctggttccctgaggaccagcgggtactgacccccaacctggtggccgccctgccccccag cacccatGGGGCAGGTTGGCAGCTGTTTTGCAGGACTGTATGGTCAGCACACTCGGGGCCTACACGGATGGCC I474V ATC to GTC ACAGCCGTCGCCCGCTGCGCCCCAGATGAGGAGCTGCTGAGCTGCTCCAGTTTCTCCAGGAGTGGGAAGCGG CGGGGCGAGCGCATGGAGGCCCAAGGGGGCAAGCTGGTCTGCCGGGCCCACAACGCTTTTGGGGGTGAGGG TGTCTACGCCATTGCCAGGTGCTGCCTGCTACCCCAGGCCAACTGCAGCGTCCACACAGCTCCACCAGCTGAG GCCAGCATGGGGACCCGTGTCCACTGCCACCAACAGGGCCACGTCCTCACAGGCTGCAGCTCCCACTGGGAG GTGGAGGACCTTGGCACCCACAAGCCGCCTGTGCTGAGGCCACGAGGTCAGCCCAACCAGTGCGTGGGCCAC AGGGAGGCCAGCATCCACGCTTCCTGCTGCCATGCCCCAGGTCTGGAATGCAAAGTCAAGGAGCATGGAA Q619P CAG to CCG E620G GAG to GGG TCCCGGCCCCTCAGGAGCAGGTGACCGTGGCCTGCGAGGAGGGCTGGACCCTGACTGGCTGCAGTGCCCTCC CTGGGACCTCCCACGTCCTGGGGGCCTACGCCGTAGACAACACGTGTGTAGTCAGGAGCCGGGACGTCAGCA E670G GAG to GGG CTACAGGCAGCACCAGCGAAGAGGCCGTGACAGCCGTTGCCATCTGCTGCCGGAGCCGGCACCTGGCGCAGG CCTCCCAGGAGCTCCAGTGAC h ATGGGCACCGTCAGCTCCAGGCGGTCCTGGTGGCCGCTGCCACTGCTGCTGCTGCTGCTGCTGCTCCTGGGTC 35 R46L CGT to CTT CCGCGGGCGCCCGTGCGCAGGAGGACGAGGACGGCGACTACGAGGAGCTGGTGCTAGCCTTGCGTTCCG A53V GCC to GTC AGGAGGACGGCCTGGCCGAAGCACCCGAGCACGGAACCACAGCCACCTTCCACCGCTGCGCCAAGGAT CCGTGGAGGTTGCCTGGCACCTACGTGGTGGTGCTGAAGGAGGAGACCCACCTCTCGCAGTCAGAGCG CACTGCCCGCCGCCTGCAGGCCCAGGCTGCCCGCCGGGGATACCTCACCAAGATCCTGCATGTCTTCC ATGGCCTTCTTCCTGGCTTCCTGGTGAAGATGAGTGGCGACCTGCTGGAGCTGGCCTTGAAGTTGCCC CATGTCGACTACATCGAGGAGGACTCCTCTGTCTTTGCCCAGagcatcccgtggaacctggagcggattacccctcca cggtaccgggcggatgaataccagccccccgacggaggcagcctggtggaggtgtatctcctagacaccagcatacagagtgaccaccgggaa atcgagggcagggtcatggtcaccgacttcgagaatgtgcccgaggaggacgggacccgcttccacagacaggccagcaagtgtgacagtcat ggcacccacctggcaggggtggtcagcggccgggatgccggcgtggccaagggtgccagcatgcgcagcctgcgcgtgctcaactgccaaggg aagggcacggttagcggcaccctcataggcctggagtttattcggaaaagccagctggtccagcctgtggggccactggtggtgctgctgcccct ggcgggtgggtacagccgcgtcctcaacgccgcctgccagcgcctggcgagggctggggtcgtgctggtcaccgctgccggcaacttccgggac gatgcctgcctctactccccagcctcagctcccgaggtcatcacagttggggccaccaatgcccaagaccagccggtgaccctggggactttggg gaccaactttggccgctgtgtggacctctttgccccaggggaggacatcattggtgcctccagcgactgcagcacctgctttgtgtcacagagtgg gacatcacaggctgctgcccacgtggctggcattgcagccatgatgctgctgccgagccggagctaccctggccgagttgaggcagagactg N425S AAT to AGT A443T GCC to ACC atccacttctctgccaaagatgtcatcaatgaggcctggttccctgaggaccagcgggtactgacccccaacctggtggccaccctgccccccag cacccatGGGGCAGGTTGGCAGCTGTTTTGCAGGACTGTATGGTCAGCACACTCGGGGCCTACACGGATGGCC I474V ATC to GTC ACAGCCATCGCCCGCTGCGCCCCAGATGAGGAGCTGCTGAGCTGCTCCAGTTTCTCCAGGAGTGGGAAGCGG CGGGGCGAGCGCATGGAGGCCCAAGGGGGCAAGCTGGTCTGCCGGGCCCACAACGCTTTTGGGGGTGAGGG TGTCTACGCCATTGCCAGGTGCTGCCTGCTACCCCAGGCCAACTGCAGCGTCCACACAGCTCCACCAGCTGAG GCCAGCATGGGGACCCGTGTCCACTGCCACCAACAGGGCCACGTCCTCACAGGCTGCAGCTCCCACTGGGAG GTGGAGGACCTTGGCACCCACAAGCCGCCTGTGCTGAGGCCACGAGGTCAGCCCAACCAGTGCGTGGGCCAC AGGGAGGCCAGCATCCACGCTTCCTGCTGCCATGCCCCAGGTCTGGAATGCAAAGTCAAGGAGCATGGAA Q619P CAG to CCG E620G GAG to GGG TCCCGGCCCCTCCGGAGCAGGTGACCGTGGCCTGCGAGGAGGGCTGGACCCTGACTGGCTGCAGTGCCCTCC CTGGGACCTCCCACGTCCTGGGGGCCTACGCCGTAGACAACACGTGTGTAGTCAGGAGCCGGGACGTCAGCA E670G GAG to GGG CTACAGGCAGCACCAGCGAAGAGGCCGTGACAGCCGTTGCCATCTGCTGCCGGAGCCGGCACCTGGCGCAGG CCTCCCAGGAGCTCCAGTGAC aj ATGGGCACCGTCAGCTCCAGGCGGTCCTGGTGGCCGCTGCCACTGCTGCTGCTGCTGCTGCTGCTCCTGGGTC 36 R46L CGT to CTT CCGCGGGCGCCCGTGCGCAGGAGGACGAGGACGGCGACTACGAGGAGCTGGTGCTAGCCTTGCTTTCCG A53V GCC to GTC AGGAGGACGGCCTGGCCGAAGCACCCGAGCACGGAACCACAGCCACCTTCCACCGCTGCGCCAAGGAT CCGTGGAGGTTGCCTGGCACCTACGTGGTGGTGCTGAAGGAGGAGACCCACCTCTCGCAGTCAGAGCG CACTGCCCGCCGCCTGCAGGCCCAGGCTGCCCGCCGGGGATACCTCACCAAGATCCTGCATGTCTTCC ATGGCCTTCTTCCTGGCTTCCTGGTGAAGATGAGTGGCGACCTGCTGGAGCTGGCCTTGAAGTTGCCC CATGTCGACTACATCGAGGAGGACTCCTCTGTCTTTGCCCAGagcatcccgtggaacctggagcggattacccctcca cggtaccgggcggatgaataccagccccccgacggaggcagcctggtggaggtgtatctcctagacaccagcatacagagtgaccaccgggaa atcgagggcagggtcatggtcaccgacttcgagaatgtgcccgaggaggacgggacccgcttccacagacaggccagcaagtgtgacagtcat ggcacccacctggcaggggtggtcagcggccgggatgccggcgtggccaagggtgccagcatgcgcagcctgcgcgtgctcaactgccaaggg aagggcacggttagcggcaccctcataggcctggagtttattcggaaaagccagctggtccagcctgtggggccactggtggtgctgctgcccct ggcgggtgggtacagccgcgtcctcaacgccgcctgccagcgcctggcgagggctggggtcgtgctggtcaccgctgccggcaacttccgggac gatgcctgcctctactccccagcctcagctcccgaggtcatcacagttggggccaccaatgcccaagaccagccggtgaccctggggactttggg gaccaactttggccgctgtgtggacctctttgccccaggggaggacatcattggtgcctccagcgactgcagcacctgctttgtgtcacagagtgg gacatcacaggctgctgcccacgtggctggcattgcagccatgatgctgctgccgagccggagctaccctggccgagttgaggcagagactg N425S AAT to AGT A443T GCC to ACC atccacttctctgccaaagatgtcatcaatgaggcctggttccctgaggaccagcgggtactgacccccaacctggtggccgccctgccccccag cacccatGGGGCAGGTTGGCAGCTGTTTTGCAGGACTGTATGGTCAGCACACTCGGGGCCTACACGGATGGCC I474V ATC to GTC ACAGCCGTCGCCCGCTGCGCCCCAGATGAGGAGCTGCTGAGCTGCTCCAGTTTCTCCAGGAGTGGGAAGCGG CGGGGCGAGCGCATGGAGGCCCAAGGGGGCAAGCTGGTCTGCCGGGCCCACAACGCTTTTGGGGGTGAGGG TGTCTACGCCATTGCCAGGTGCTGCCTGCTACCCCAGGCCAACTGCAGCGTCCACACAGCTCCACCAGCTGAG GCCAGCATGGGGACCCGTGTCCACTGCCACCAACAGGGCCACGTCCTCACAGGCTGCAGCTCCCACTGGGAG GTGGAGGACCTTGGCACCCACAAGCCGCCTGTGCTGAGGCCACGAGGTCAGCCCAACCAGTGCGTGGGCCAC AGGGAGGCCAGCATCCACGCTTCCTGCTGCCATGCCCCAGGTCTGGAATGCAAAGTCAAGGAGCATGGAA Q619P CAG to CCG E620G GAG to GGG TCCCGGCCCCTCAGGAGCAGGTGACCGTGGCCTGCGAGGAGGGCTGGACCCTGACTGGCTGCAGTGCCCTCC CTGGGACCTCCCACGTCCTGGGGGCCTACGCCGTAGACAACACGTGTGTAGTCAGGAGCCGGGACGTCAGCA E670G GAG to GGG CTACAGGCAGCACCAGCGAAGAGGCCGTGACAGCCGTTGCCATCTGCTGCCGGAGCCGGCACCTGGCGCAGG CCTCCCAGGAGCTCCAGTGAC q ATGGGCACCGTCAGCTCCAGGCGGTCCTGGTGGCCGCTGCCACTGCTGCTGCTGCTGCTGCTGCTCCTGGGTC 37 R46L CGT to CTT CCGCGGGCGCCCGTGCGCAGGAGGACGAGGACGGCGACTACGAGGAGCTGGTGCTAGCCTTGCGTTCCG A53V GCC to GTC AGGAGGACGGCCTGGTCGAAGCACCCGAGCACGGAACCACAGCCACCTTCCACCGCTGCGCCAAGGAT CCGTGGAGGTTGCCTGGCACCTACGTGGTGGTGCTGAAGGAGGAGACCCACCTCTCGCAGTCAGAGCG CACTGCCCGCCGCCTGCAGGCCCAGGCTGCCCGCCGGGGATACCTCACCAAGATCCTGCATGTCTTCC ATGGCCTTCTTCCTGGCTTCCTGGTGAAGATGAGTGGCGACCTGCTGGAGCTGGCCTTGAAGTTGCCC CATGTCGACTACATCGAGGAGGACTCCTCTGTCTTTGCCCAGagcatcccgtggaacctggagcggattacccctcca cggtaccgggcggatgaataccagccccccgacggaggcagcctggtggaggtgtatctcctagacaccagcatacagagtgaccaccgggaa atcgagggcagggtcatggtcaccgacttcgagaatgtgcccgaggaggacgggacccgcttccacagacaggccagcaagtgtgacagtcat ggcacccacctggcaggggtggtcagcggccgggatgccggcgtggccaagggtgccagcatgcgcagcctgcgcgtgctcaactgccaaggg aagggcacggttagcggcaccctcataggcctggagtttattcggaaaagccagctggtccagcctgtggggccactggtggtgctgctgcccct ggcgggtgggtacagccgcgtcctcaacgccgcctgccagcgcctggcgagggctggggtcgtgctggtcaccgctgccggcaacttccgggac gatgcctgcctctactccccagcctcagctcccgaggtcatcacagttggggccaccaatgcccaagaccagccggtgaccctggggactttggg gaccaactttggccgctgtgtggacctctttgccccaggggaggacatcattggtgcctccagcgactgcagcacctgctttgtgtcacagagtgg gacatcacaggctgctgcccacgtggctggcattgcagccatgatgctgctgccgagccggagctaccctggccgagttgaggcagagactg N425S AAT to AGT A443T GCC to ACC atccacttctctgccaaagatgtcatcaatgaggcctggttccctgaggaccagcgggtactgacccccaacctggtggccgccctgccccccag cacccatGGGGCAGGTTGGCAGCTGTTTTGCAGGACTGTATGGTCAGCACACTCGGGGCCTACACGGATGGCC I474V ATC to GTC ACAGCCATCGCCCGCTGCGCCCCAGATGAGGAGCTGCTGAGCTGCTCCAGTTTCTCCAGGAGTGGGAAGCGG CGGGGCGAGCGCATGGAGGCCCAAGGGGGCAAGCTGGTCTGCCGGGCCCACAACGCTTTTGGGGGTGAGGG TGTCTACGCCATTGCCAGGTGCTGCCTGCTACCCCAGGCCAACTGCAGCGTCCACACAGCTCCACCAGCTGAG GCCAGCATGGGGACCCGTGTCCACTGCCACCAACAGGGCCACGTCCTCACAGGCTGCAGCTCCCACTGGGAG GTGGAGGACCTTGGCACCCACAAGCCGCCTGTGCTGAGGCCACGAGGTCAGCCCAACCAGTGCGTGGGCCAC AGGGAGGCCAGCATCCACGCTTCCTGCTGCCATGCCCCAGGTCTGGAATGCAAAGTCAAGGAGCATGGAA Q619P CAG to CCG E620G GAG to GGG TCCCGGCCCCTCAGGAGCAGGTGACCGTGGCCTGCGAGGAGGGCTGGACCCTGACTGGCTGCAGTGCCCTCC CTGGGACCTCCCACGTCCTGGGGGCCTACGCCGTAGACAACACGTGTGTAGTCAGGAGCCGGGACGTCAGCA E670G GAG to GGG CTACAGGCAGCACCAGCGAAGGGGCCGTGACAGCCGTTGCCATCTGCTGCCGGAGCCGGCACCTGGCGCAGG CCTCCCAGGAGCTCCAGTGAC TABLE 7 Human VH3-23 Variant Alleles VH3-23 Cumulative allele haplotype frequency SNPs a (=VH3-23*04) 0.0983 rs56069819 d 0.0087 rs56069819 rs61750837 rs61752504 e 0.0046 rs56069819 rs1064090 rs1055799 j 0.0009 rs56069819 rs1055799 u 0.0005 rs56069819 rs1064091 s 0.0005 rs56069819 rs1064091 rs61752504 rs61750837 r 0.0005 rs56069819 rs1064090 TOTAL: 0.114 TABLE 8 Exemplary anti-PCSK9 antibodies and/or antibody fragments SEQ ID NOs comprising an anti-PCSK9 Patent or monoclonal antibody or fragment thereof patent Pblication Light chain complementary determining regions US20120020975 A1 (CDRL) SEQ ID NO: 5, 7, 9, 10, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, 46, 270, 271, 272, 273, 275, 277, 286, 287, 288, 297, 299, 301, 405, 407, 409, 411, 413, 415, 417, 421, 425, 429, 433, 437, 441, 445, 449, 453, 457, 461, 465, 469, 473, 477, 481, 485; Heavy chain complementary determining regions (CDRH) SEQ ID NO: 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 61, 62, 64, 65, 67, 69, 71, 72, 74, 76, 77, 78, 79, 80, 81, 83, 85, 87, 89, 91, 278, 289, 290, 291, 292, 298, 300, 302, 401, 404, 406, 408, 410, 412, 414, 416, 419, 423, 427, 431, 435, 439, 443, 447, 451, 455, 459, 463, 467, 471, 475, 479, 483; CDRL SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, US20120027765A1 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, 46, 405, 407, 409, 411, 413, 415, 417, 465; CDRH SEQ ID NO: 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 62, 64, 65, 67, 69, 71, 72, 74, 76, 77, 78, 79, 80, 81, 83, 85, 87, 89, 91, 404, 406, 408, 410, 412, 414, 416, 463; CDRL SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, U.S. Pat.\",\n \"No.\",\n \"17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 8,168,762B2 33, 35, 36, 37, 38, 39, 40, 42, 44, 46, 405, 407, 409, 411, 413, 415, 417, 465; CDRH SEQ ID NO: 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 62, 64, 65, 67, 69, 71, 72, 74, 76, 77, 78, 79, 80, 81, 83, 85, 87, 89, 91, 404, 406, 408, 410, 412, 414, 416, 463; CDRL SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, US20120020976A1 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, 46, 222, 229, 238, 405, 407, 409, 411, 413, 415, 417; CDRH SEQ ID NO: 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 62, 64, 65, 67, 69, 71, 72, 74, 76, 77, 78, 79, 80, 81, 83, 85, 87, 89, 91, 247, 256, 265, 404, 406, 408, 410, 412, 414, 416; CDRL SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, US20130085265A1 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, 46, 405, 407, 409, 411, 413, 415, 417, 461, 465, 485; CDRH SEQ ID NO: 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 62, 64, 65, 67, 69, 71, 72, 74, 76, 77, 78, 79, 80, 81, 83, 85, 87, 89, 91, 404, 406, 408, 410, 412, 414, 416, 459, 463, 483; CDRL SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, US20130079501A1 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, 46, 405, 407, 409, 411, 413, 415, 417, 461, 465, 485; CDRH SEQ ID NO: 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 62, 64, 65, 67, 69, 71, 72, 74, 76, 77, 78, 79, 80, 81, 83, 85, 87, 89, 91, 404, 406, 408, 410, 412, 414, 416, 459, 463, 483; CDRL SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, US20120213797A1 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, 46, 405, 407, 409, 411, 413, 415, 417, 158, 162, 395, 473, 477; CDRH SEQ ID NO: 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 62, 64, 65, 67, 69, 71, 72, 74, 76, 77, 78, 79, 80, 81, 83, 85, 87, 89, 91, 404, 406, 408, 410, 412, 414, 416, 180, 175, 308, 368, 471, 475; CDRL SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, US20120251544A1 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, 46, 405, 407, 409, 411, 413, 415, 417; CDRH SEQ ID NO: 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 62, 64, 65, 67, 69, 71, 72, 74, 76, 77, 78, 79, 80, 81, 83, 85, 87, 89, 91, 404, 406, 408, 410, 412, 414, 416; CDRL SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, US20130052201A1 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, 46, 405, 407, 409, 411, 413, 415, 417, 461, 465, 485; CDRH SEQ ID NO: 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 62, 64, 65, 67, 69, 71, 72, 74, 76, 77, 78, 79, 80, 81, 83, 85, 87, 89, 91, 404, 406, 408, 410, 412, 414, 416, 459, 463, 483; CDRL SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, US20130058944A1 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, 46, 405, 407, 409, 411, 413, 415, 417, 461, 465, 485; CDRH SEQ ID NO: 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 62, 64, 65, 67, 69, 71, 72, 74, 76, 77, 78, 79, 80, 81, 83, 85, 87, 89, 91, 404, 406, 408, 410, 412, 414, 416, 459, 463, 483; CDRL SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, US20130079502A1 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, 46, 405, 407, 409, 411, 413, 415, 417; CDRH SEQ ID NO: 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 62, 64, 65, 67, 69, 71, 72, 74, 76, 77, 78, 79, 80, 81, 83, 85, 87, 89, 91, 404, 406, 408, 410, 412, 414, 416; CDRL SEQ ID NO: 5, 7, 9, 10, 12, 13, 15, 16, US20130245235A1 17, 18, 19, 20, 21, 22, 23, 24, 26, 28, 30, 31, 32, 33, 35, 36, 37, 38, 39, 40, 42, 44, 46, 405, 407, 409, 411, 413, 415, 417; CDRH SEQ ID NO: 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 60, 62, 64, 65, 67, 69, 71, 72, 74, 76, 77, 78, 79, 80, 81, 83, 85, 87, 89, 91, 404, 406, 408, 410, 412, 414, 416; TABLE 9 Human variable & constant variants distributed over several human ethnic populations - useful for ligand tailoring Nucleotide Hom Human Variation2 Freq7 Gene Example Amino Acid (NCBI dbSNP Variant (Het + Segment Human Position & reference Nucleotide Human No.\",\n \"Het Hom Cum Type Allele1 Variation number)3 Position Populations4 Individs5 Freq6 freq8) Freq9 IGHG1 IGHG1*01 204D GAT 14:106208086 A 153 0.400 0.096 0.296 (CH3 (forward strand) (European (0.496) variation) ancestry) IGHG1*03 204E GAG 14:106208086 A 366 0.400 0.504 0.704 (CH3 (rs1045853) (forward strand) (European (0.904) variation) ancestry IGHG1*01 206L CTG 14:106208082 A 0.358 0.104 0.283 (CH3 (forward strand) (European (0.462) variation) ancestry) IGHG1*03 206M ATG 14:106208082 A 0.358 0.538 0.717 (CH3 (rs11621259) (forward strand) (European (0.896) variation) ancestry) IGHG2 IGHG2*01 72P CCC 14:106110914 B 0.336 0.540 0.708 (CH1 (forward strand) (0.876) variation) IGHG2*02 72T ACC 14:106110914 B 0.336 0.124 0.292 (CH1 (rs11627594) (forward strand) variation) IGHG2*01 75N AAC 14:106110904 A 0.007 0.993 0.997 (CH1 (forward strand) variation) IGHG2*04 75S AGC 14:106110904 A 0.007 0.004 (CH1 (rs201590297) (forward strand) variation) IGHG2*01 76F TTC (CH1 variation) IGHG2*04 76L TTG (CH1 variation) IGHG2*01 161V GTG 14:10611013 B 0.342 0.539 0.711 (CH2 (forward strand) (0.881) variation) IGHG2*02 161M ATG 14:10611013 B 0.342 0.118 0.289 (CH2 (rs8009156) (forward strand) (0.46) variation) IGHG2*01 257A GCC 14:106109752 C 0.199 0.493 0.592 (CH3 (forward strand) (0.692) variation) D 0.007 0.992 0.995 (0.999) IGHG2*06 257S TCC 14:106109752 C 0.199 0.308 0.408 (CH3 (rs4983499) (forward strand) (0.507) variation) D 0.007 0.002 0.005 (0.009) Table Footnotes: 1IMGT notation (ww.imgt.org); refer to figures for other alleles comprising this variation.\",\n \"2SNP Underlined in Codon.\",\n \"3NCBI dbSNP Build 138 released on Apr.\",\n \"25, 2013.4Human population used for representative variant frequency analysis.\",\n \"Populations A This population included 662 participants of European descent from the ClinSeq project, all of whom had undergone whole-exome sequencing using Agilent's 38Mb or 50Mb capture kit.\",\n \"B 1000 Genomes database.\",\n \"C ESP6500: African_American.\",\n \"D ESP6500: European_American.\",\n \"5Number of individuals in representative population found to have the allele.\",\n \"6Heterozygous human genotype frequency, ie, cumulative frequency of all genotypes having one occurrence of the variant allele and one occurrence of another allele (heterozygous state), eg, ac genotype in the population.\",\n \"7Homozygous human genotype frequency, ie, cumulative frequency of two occurrences of the variant allele (homozygous state), eg, cc genotype in the population.\",\n \"8Total human genotype frequency, ie, total of heterozygous plus homozygous human genotype frequencies.\",\n \"9Cumulative human allele frequency of all occurrences of the variant allele in the population.\",\n \"TABLE 10 FURTHER SEQUENCES SEQ ID Human NO: Allele Nucleotide/Amino Acid Sequence HEAVY CHAIN ALLELES 41 IGHG1*01 gcctccaccaagggcccatcggtcttccccctggcaccctcctccaaga (CH1 + Hinge + gcacctctggg CH2 + CH3 + CH- ggcacagcggccctgggctgcctggtcaaggactacttccccgaaccgg S) tgacggtgtcg tggaactcaggcgccctgaccagcggcgtgcacaccttcccggctgtcc tacagtcctca ggactctactccctcagcagcgtggtgaccgtgccctccagcagcttgg gcacccagacc tacatctgcaacgtgaatcacaagcccagcaacaccaaggtggacaaga aagttgagccc aaatcttgtgacaaaactcacacatgcccaccgtgcccagcacctgaac tcctgggggga ccgtcagtcttcctcttccccccaaaacccaaggacaccctcatgatct cccggacccct gaggtcacatgcgtggtggtggacgtgagccacgaagaccctgaggtca agttcaactgg tacgtggacggcgtggaggtgcataatgccaagacaaagccgcgggagg agcagtacaac agcacgtaccgggtggtcagcgtcctcaccgtcctgcaccaggactggc tgaatggcaag gagtacaagtgcaaggtctccaacaaagccctcccagcccccatcgaga aaaccatctcc aaagccaaagggcagccccgagaaccacaggtgtacaccctgcccccat cccgggatgag ctgaccaagaaccaggtcagcctgacctgcctggtcaaaggcttctatc ccagcgacatc gccgtggagtgggagagcaatgggcagccggagaacaactacaagacca cgcctcccgtg ctggactccgacggctccttcttcctctacagcaagctcaccgtggaca agagcaggtgg cagcaggggaacgtcttctcatgctccgtgatgcatgaggctctgcaca accactacacg cagaagagcctctccctgtctccgggtaaa 42 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSG VHTFPAVLQSS GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTC PPCPAPELLGG PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHN AKTKPREEQYN STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREP QVYTLPPSRDE LTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTIPPVLDSDGSFFL YSKLTVDKSRW QQGNVFSCSVMHEALHNHYTQKSLSLSPGK D = position 204 L = position 206 43 IGHG2*01 gcctccaccaagggcccatcggtcttccccctggcgccctgctccagga (CH1 + Hinge + gcacctccgag CH2 + CH3 + CH- agcacagccgccctgggctgcctggtcaaggactacttccccgaaccgg S) tgacggtgtcg tggaactcaggcgctctgaccagcggcgtgcacaccttcccagctgtcc tacagtcctca ggactctactccctcagcagcgtggtgaccgtgccctccagcaacttcg gcacccagacc tacacctgcaacgtagatcacaagcccagcaacaccaaggtggacaaga cagttgagcgc aaatgttgtgtcgagtgcccaccgtgcccagcaccacctgtggcaggac cgtcagtcttc ctcttccccccaaaacccaaggacaccctcatgatctcccggacccctg aggtcacgtgc gtggtggtggacgtgagccacgaagaccccgaggtccagttcaactggt acgtggacggc gtggaggtgcataatgccaagacaaagccacgggaggagcagttcaaca gcacgttccgt gtggtcagcgtcctcaccgttgtgcaccaggactggctgaacggcaagg agtacaagtgc aaggtctccaacaaaggcctcccagcccccatcgagaaaaccatctcca aaaccaaaggg cagccccgagaaccacaggtgtacaccctgcccccatcccgggaggaga tgaccaagaac caggtcagcctgacctgcctggtcaaaggcttctaccccagcgacatcg ccgtggagtgg gagagcaatgggcagccggagaacaactacaagaccacacctcccatgc tggactccgac ggctccttcttcctctacagcaagctcaccgtggacaagagcaggtggc agcaggggaac gtcttctcatgctccgtgatgcatgaggctctgcacaaccactacacgc agaagagcctc tccctgtctccgggtaaa 44 ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSG VHTFPAVLQSS GLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPC PAPPVAGPSVF LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTK PREEQFNSTFR VVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYT LPPSREEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKL TVDKSRWQQGN VFSCSVMHEALHNHYTQKSLSLSPGK P = position 72 N = position 75 F = position 76 V = position 161 A = position 257 45 IGHV1-18*01 caggttcagctggtgcagtctggagctgaggtgaagaagcctggggcct cagtgaaggtc tcctgcaaggcttctggttacacctttaccagctatggtatcagctggg tgcgacaggcc cctggacaagggcttgagtggatgggatggatcagcgcttacaatggta acacaaactat gcacagaagctccagggcagagtcaccatgaccacagacacatccacga gcacagcctac atggagctgaggagcctgagatctgacgacacggccgtgtattactgtg cgagaga 46 QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAP GQGLEWMGWISAYNGNTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDD TAVYYCAR 47 IGHV1-46*01 caggtgcagctggtgcagtctggggctgaggtgaagaagcctggggcct cagtgaaggtt tcctgcaaggcatctggatacaccttcaccagctactatatgcactggg tgcgacaggcc cctggacaagggcttgagtggatgggaataatcaaccctagtggtggta gcacaagctac gcacagaagttccagggcagagtcaccatgaccagggacacgtccacga gcacagtctac atggagctgagcagcctgagatctgaggacacggccgtgtattactgtg cgagaga 48 QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAP GQGLEWMGIINPSGGSTSYAQKFQGRVTMTRDTSTSTVYMELSSLRSED TAVYYCAR LIGHT CHAIN ALLELES 49 IGKC*01 cgaactgtggctgcaccatctgtcttcatcttcccgccatctgatgagc agttgaaatct ggaactgcctctgttgtgtgcctgctgaataacttctatcccagagagg ccaaagtacag tggaaggtggataacgccctccaatcgggtaactcccaggagagtgtca cagagcaggac agcaaggacagcacctacagcctcagcagcaccctgacgctgagcaaag cagactacgag aaacacaaagtctacgcctgcgaagtcacccatcagggcctgagctcgc ccgtcacaaag agcttcaacaggggagagtgt 50 RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS GNSQESVTEQD SKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC V = position 84 C = position 87 51 IGLC2*01 ggtcagcccaaggctgccccctcggtcactctgttcccgccctcctctg aggagcttcaa gccaacaaggccacactggtgtgtctcataagtgacttctacccgggag ccgtgacagtg gcttggaaagcagatagcagccccgtcaaggcgggagtggagaccacca caccctccaaa caaagcaacaacaagtacgcggccagcagctatctgagcctgacgcctg agcagtggaag tcccacagaagctacagctgccaggtcacgcatgaagggagcaccgtgg agaagacagtg gcccctacagaatgttca 52 GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPV KAGVETTTPSK QSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 53 IGKV4-1*01 atggtgttgcagacccaggtcttcatttctctgttgctctggatctctg gtgcctacggg gacatcgtgatgacccagtctccagactccctggctgtgtctctgggcg agagggccacc atcaactgcaagtccagccagagtgttttatacagctccaacaataaga actacttagct tggtaccagcagaaaccaggacagcctcctaagctgctcatttactggg catctacccgg gaatccggggtccctgaccgattcagtggcagcgggtctgggacagatt tcactctcacc atcagcagcctgcaggctgaagatgtggcagtttattactgtcagcaat attatagtact cctcc 54 DIVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKNYLA WYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDV AVYYCQQYYST P 55 IGKV1-13*02 atggacatgagggtccccgctcagctcctggggcttctgctgctctggc tcccagcaggt gccagatgtgccatccagttgacccagtctccatcctccctgtctgcat ctgtaggagac agagtcaccatcacttgccgggcaagtcagggcattagcagtgctttag cctggtatcag cagaaaccagggaaagctcctaagctcctgatctatgatgcctccagtt tggaaagtggg gtcccatcaaggttcagcggcagtggatctgggacagatttcactctca ccatcagcagc ctgcagcctgaagattttgcaacttattactgtcaacagtttaatagtt accctcagtgc cagatgtgccatccagttgacccagtctccatcctccctgtctgcatct gtaggagacag agtcaccatcacttgccgggcaagtcagggcattagcagtgctttagcc tggtatcagca gaaaccagggaaagctcctaagctcctgatctatgatgcctccagtttg gaaagtggggt cccatcaaggttcagcggcagtggatctgggacagatttcactctcacc atcagcagcct gcagcctgaagattttgcaacttattactgtcaacagtttaatagttac cctca 57 IGKJ2*01 tgtacacttttggccaggggaccaagctggagatcaaac 58 YTFGQGTKLEIK 59 IGLJ2*01 tgtggtattcggcggagggaccaagctgaccgtcctag 60 VVFGGGTKLTVL 61 An IGHG1*01 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSG Heavy Chain VHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKV Constant EPKSCDKTHTCPPCPAPELLGGPS Region VFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAK TKPREEQYNST YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV YTLPPSRDELT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS KLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 62 An IGKC*01 RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS Kappa Light GNSQESVIEQDSKDSTYSLSSILTLSKADYEKHKVYACEVTHQGLSSPV Chain TKSFNRGEC Constant Region 63 An IGHG2*01 ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSG Heavy Chain VHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTV Constant ERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSH Region EDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGK EYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 64 An IGLC2*01 QPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVK Lambda AGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKT Light Chain VAPTECS Constant Region 65 An IGHG2*01 ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSG Heavy Chain VHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTV Constant ERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSH Region EDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGK EYKCKVSNKGLPSSIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLT CLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKS RWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 66 An IGKC*01 RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQS Kappa Light GNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV Chain TKSFNRGEC Constant Region\"\n ]\n]"},"source":{"kind":"string","value":"Patent_15872025"}}},{"rowIdx":4493986,"cells":{"text":{"kind":"list like","value":[["COMPOSITION AND METHOD FOR TREATMENT OF SYMPTOMS ASSOCIATED WITH VARIOUS SKIN CONDITIONS","Compositions containing imidazole-based compounds, and optionally, colloidal oatmeal, for the treatment, prevention, and management of symptoms, conditions, diseases, and disorders of the skin.","Also, methods for the treatment, prevention, and management of symptoms, conditions, diseases, and disorders of the skin using compositions containing imidazole-based compounds, and optionally, colloidal oatmeal."],["1.A composition comprising colloidal oatmeal and an imidazole compound of the formula wherein: R1 is hydrogen, alkyl or aryl; R6 is OR10 or OC(O)R10; R7 is OR11 or OC(O)R11; R8 is OR12 or OC(O)R12; and R9 is hydrogen, CH2OR13 or CH2OC(O)R13; and each of R10, R11, R12 and R13 is independently hydrogen or lower alkyl, and pharmaceutically, dermatologically, or cosmetically acceptable salts thereof, contained in a dermatologically acceptable carrier.","2.The composition of claim 1, in the form of a spray, cream, gel, lotion, or ointment.","3.The composition of claim 1, wherein the carrier comprises one or more excipients selected from the group consisting of surfactants, solvents, tonicity modifiers, thickeners, emulsifiers, preservatives, dispersants, buffers, stabilizers, fragrances, colorants, and flavorings.","4.The composition of claim 1, further comprising one or more compounds or compositions selected from the group consisting of antipruritics, emollients, antiseptics, antifungals, antiinflammatories, immunosuppressants, psoriasis agents, anti-cancer agents, antibiotics, antiparasitics, antioxidants, antibacterials, antimicrobials, antiretrovirals, moisturizers, sunscreens, NSAIDs, hormones, steroids, analgesics, antihistamines, and antipyretics.","5.The composition of claim 1, comprising 0.01% to 10% by weight of 2-acetyl-4-tetrahydroxybutylimidazole or a pharmaceutically, dermatologically, or cosmetically acceptable salt thereof and 0.01% to 25% by weight of the colloidal oatmeal.","6.The composition of claim 5, comprising 0.1% to 5% by weight of 2-acetyl-4-tetrahydroxybutylimidazole or a pharmaceutically, dermatologically, or cosmetically acceptable salt thereof and 0.1% to 10% by weight of the colloidal oatmeal.","7.The composition of claim 6, comprising 0.5% to 2% by weight of 2-acetyl-4-tetrahydroxybutylimidazole or a pharmaceutically, dermatologically, or cosmetically acceptable salt thereof and 0.5% to 2% by weight of the colloidal oatmeal."],[" FIELD OF THE INVENTION This invention relates to compositions containing imidazole-based compounds, and optionally, colloidal oatmeal, and to methods of their use for the treatment, prevention, and management of symptoms, conditions, diseases, and disorders of the skin."],[" SUMMARY OF THE INVENTION One aspect of the invention relates to a method of treating, managing, or preventing a dermatological or skin condition, which comprises topically administering to a subject in need thereof a therapeutically or prophylactically effective composition comprising an imidazole compound of the formula: wherein: R 1 is hydrogen, alkyl or aryl; R 6 is OR 10 or OC(O)R 10 ; R 7 is OR 11 or OC(O)R 11 ; R 8 is OR 12 or OC(O)R 12 ; and R 9 is hydrogen, CH 2 OR 13 or CH 2 OC(O)R 13 ; and each of R 10 , R 11 , R 12 and R 13 is independently hydrogen or lower alkyl, and pharmaceutically, dermatologically, or cosmetically acceptable salts thereof.","Another aspect of the invention relates to a method of caring for skin, which comprises topically administering to the skin of a subject in need thereof a composition comprising the imidazole compound in an amount and for a time sufficient to effect a change in the skin.","Another aspect of the invention relates to a method of delivering or depositing a benefit agent onto skin, which comprises topically administering to the skin of a subject a composition comprising the imidazole compound contained in a dermatologically acceptable carrier.","Another aspect of the invention relates to a method of suppressing a dermatologic immune response in a patient in need thereof, comprising topically administering an effective composition comprising the imidazole compound contained in a dermatologically acceptable carrier.","Another aspect of the invention relates to a composition comprising an imidazole compound of the formula: wherein: R 1 is hydrogen, alkyl or aryl; R 6 is OR 10 or OC(O)R 10 ; R 7 is OR 11 or OC(O)R 11 ; R 8 is OR 12 or OC(O)R 12 ; and R 9 is hydrogen, CH 2 OR 13 or CH 2 OC(O)R 13 ; and each of R 10 , R 11 , R 12 and R 13 is independently hydrogen or lower alkyl, and pharmaceutically, dermatologically, or cosmetically acceptable salts thereof.","Another aspect of the invention relates to compositions containing combinations of imidazole-based compounds and, optionally, colloidal oatmeal, and to methods of their use for the treatment, prevention, and management of inflammatory or immune-mediated symptoms, conditions, diseases, and disorders of the skin.","Another aspect of the invention relates to combinations of imidazole-based compounds and, optionally, colloidal oatmeal, and to methods of their use for the treatment, prevention, and management of various skin symptoms, conditions, diseases, and disorders.","Another aspect of the invention relates to combinations of imidazole-based compounds and colloidal oatmeal and to methods of their use for the treatment, prevention, and management of atopic dermatitis, seborrheic dermatitis, contact dermatitis, cutaneous sarcoidosis, drug induced photosensitivity, fixed drug eruptions, id reactions, bullous skin diseases, discoid lupus erythematosus, subacute cutaneous lupus, alopecia areata, sea bathers eruptions, psoriasis, dyshidrotic eczema, and pompholyx.","Another aspect of the invention relates to compositions and methods for treating inflammatory and/or immune-mediated dermatoses with imidazole-based compounds and combinations of imidazole-based compounds and colloidal oatmeal.","Another aspect of the invention relates to care, supplement, and pharmaceutical compositions containing imidazole-based compounds, colloidal oatmeal, and other ingredients used to treat disorders of the skin, as well as to compositions suitable for use in personal care applications, and in particular skin care compositions, which effectively deliver and/or deposit various benefit agents into and onto the skin.","Another aspect of the invention relates to compositions and methods for treating contact dermatitis.","These and further aspects of the claimed invention will now be explained in more detail.","detailed-description description=\"Detailed Description\" end=\"lead\"?"],["CROSS-REFERENCE TO RELATED APPLICATIONS This application is a divisional application, claiming benefit 35 U.S.C.","§ 120 of U.S. application Ser.","No.","14/230,494, filed Mar.","31, 2014, which claims the benefit under 35 U.S.C.","§§ 120 and 365(c) of PCT International Application No.","PCT/US2012/057431, filed Sep. 27, 2012, and claiming benefit under 35 U.S.C.","§ 119(e) of U.S.","Provisional Application No.","61/540,953, filed Sep. 29, 2011.The disclosures of U.S. application Ser.","No.","14/230,494, PCT International Application No.","PCT/US2012/057431, and U.S.","Provisional Application No.","61/540,953 are incorporated herein by reference in their entirety.","FIELD OF THE INVENTION This invention relates to compositions containing imidazole-based compounds, and optionally, colloidal oatmeal, and to methods of their use for the treatment, prevention, and management of symptoms, conditions, diseases, and disorders of the skin.","SUMMARY OF THE INVENTION One aspect of the invention relates to a method of treating, managing, or preventing a dermatological or skin condition, which comprises topically administering to a subject in need thereof a therapeutically or prophylactically effective composition comprising an imidazole compound of the formula: wherein: R1 is hydrogen, alkyl or aryl; R6 is OR10 or OC(O)R10; R7 is OR11 or OC(O)R11; R8 is OR12 or OC(O)R12; and R9 is hydrogen, CH2OR13 or CH2OC(O)R13; and each of R10, R11, R12 and R13 is independently hydrogen or lower alkyl, and pharmaceutically, dermatologically, or cosmetically acceptable salts thereof.","Another aspect of the invention relates to a method of caring for skin, which comprises topically administering to the skin of a subject in need thereof a composition comprising the imidazole compound in an amount and for a time sufficient to effect a change in the skin.","Another aspect of the invention relates to a method of delivering or depositing a benefit agent onto skin, which comprises topically administering to the skin of a subject a composition comprising the imidazole compound contained in a dermatologically acceptable carrier.","Another aspect of the invention relates to a method of suppressing a dermatologic immune response in a patient in need thereof, comprising topically administering an effective composition comprising the imidazole compound contained in a dermatologically acceptable carrier.","Another aspect of the invention relates to a composition comprising an imidazole compound of the formula: wherein: R1 is hydrogen, alkyl or aryl; R6 is OR10 or OC(O)R10; R7 is OR11 or OC(O)R11; R8 is OR12 or OC(O)R12; and R9 is hydrogen, CH2OR13 or CH2OC(O)R13; and each of R10, R11, R12 and R13 is independently hydrogen or lower alkyl, and pharmaceutically, dermatologically, or cosmetically acceptable salts thereof.","Another aspect of the invention relates to compositions containing combinations of imidazole-based compounds and, optionally, colloidal oatmeal, and to methods of their use for the treatment, prevention, and management of inflammatory or immune-mediated symptoms, conditions, diseases, and disorders of the skin.","Another aspect of the invention relates to combinations of imidazole-based compounds and, optionally, colloidal oatmeal, and to methods of their use for the treatment, prevention, and management of various skin symptoms, conditions, diseases, and disorders.","Another aspect of the invention relates to combinations of imidazole-based compounds and colloidal oatmeal and to methods of their use for the treatment, prevention, and management of atopic dermatitis, seborrheic dermatitis, contact dermatitis, cutaneous sarcoidosis, drug induced photosensitivity, fixed drug eruptions, id reactions, bullous skin diseases, discoid lupus erythematosus, subacute cutaneous lupus, alopecia areata, sea bathers eruptions, psoriasis, dyshidrotic eczema, and pompholyx.","Another aspect of the invention relates to compositions and methods for treating inflammatory and/or immune-mediated dermatoses with imidazole-based compounds and combinations of imidazole-based compounds and colloidal oatmeal.","Another aspect of the invention relates to care, supplement, and pharmaceutical compositions containing imidazole-based compounds, colloidal oatmeal, and other ingredients used to treat disorders of the skin, as well as to compositions suitable for use in personal care applications, and in particular skin care compositions, which effectively deliver and/or deposit various benefit agents into and onto the skin.","Another aspect of the invention relates to compositions and methods for treating contact dermatitis.","These and further aspects of the claimed invention will now be explained in more detail.","DETAILED DESCRIPTION OF THE INVENTION Definitions Unless otherwise indicated, the term “alkyl” means a straight chain, branched and/or cyclic (“cycloalkyl”) hydrocarbon having from 1 to 20 (e.g., 1 to 10 or 1 to 4) carbon atoms.","Alkyl moieties having from 1 to 4 carbons are referred to as “lower alkyl.” Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, t-butyl, isobutyl, pentyl, hexyl, isohexyl, heptyl, 4,4-dimethylpentyl, octyl, 2,2,4-trimethylpentyl, nonyl, decyl, undecyl and dodecyl.","Cycloalkyl moieties may be monocyclic or multicyclic, and examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and adamantyl.","Additional examples of alkyl moieties have linear, branched and/or cyclic portions (e.g., 1-ethyl-4-methyl-cyclohexyl).","The term “alkyl” includes saturated hydrocarbons as well as alkenyl and alkynyl moieties.","Unless otherwise indicated, the terms “manage,” “managing” and “management” encompass preventing the recurrence of the specified disease or disorder in a patient who has already suffered from the disease or disorder, and/or lengthening the time that a patient who has suffered from the disease or disorder remains in remission.","The terms encompass modulating the threshold, development and/or duration of the disease or disorder, or changing the way that a patient responds to the disease or disorder.","Unless otherwise indicated, the terms “prevent,” “preventing” and “prevention” contemplate an action that occurs before a patient begins to suffer from the specified disease or disorder, which inhibits or reduces the severity of the disease or disorder.","In other words, the terms encompass prophylaxis.","Unless otherwise indicated, a “prophylactically effective” means sufficient to prevent a disease or condition, or one or more symptoms associated with the disease or condition, or prevent its recurrence.","A prophylactically effective amount of a compound means an amount of therapeutic agent, alone or in combination with other agents, which provides a prophylactic benefit in the prevention of the disease.","The term “prophylactically effective” can encompass a composition that improves overall prophylaxis or enhances the prophylactic efficacy of another prophylactic agent.","Unless otherwise indicated, a “therapeutically effective” means sufficient to provide a therapeutic benefit in the treatment or management of a disease or condition, or to delay or minimize one or more symptoms associated with the disease or condition.","A therapeutically effective amount of a compound means an amount of therapeutic agent, alone or in combination with other therapies, which provides a therapeutic benefit in the treatment or management of the disease or condition.","The term “therapeutically effective” can encompass a composition that improves overall therapy, reduces or avoids symptoms or causes of a disease or condition, or enhances the therapeutic efficacy of another therapeutic agent.","Unless otherwise indicated, the terms “treat,” “treating” and “treatment” contemplate an action that occurs while a patient is suffering from the specified disease or disorder, which reduces the severity of the disease or disorder, or retards or slows the progression of the disease or disorder.","Unless otherwise indicated, the term “include” has the same meaning as “include, but are not limited to,” and the term “includes” has the same meaning as “includes, but is not limited to.” Similarly, the term “such as” has the same meaning as the term “such as, but not limited to.” Unless otherwise indicated, one or more adjectives immediately preceding a series of nouns is to be construed as applying to each of the nouns.","For example, the phrase “optionally substituted A, B, or C” has the same meaning as “optionally substituted A, optionally substituted B, or optionally substituted C.” It should be noted that a chemical moiety that forms part of a larger compound may be described herein using a name commonly accorded it when it exists as a single molecule or a name commonly accorded its radical.","It should also be noted that if the stereochemistry of a structure or a portion of a structure is not indicated with, for example, bold or dashed lines, the structure or the portion of the structure is to be interpreted as encompassing all stereoisomers of it.","Moreover, any atom shown in a drawing with unsatisfied valences is assumed to be attached to enough hydrogen atoms to satisfy the valences.","As used herein, the term “benefit agent” includes any active ingredient that is to be delivered into and/or onto the skin at a desired location, such as a cosmetic, care or pharmaceutical agent, and that is capable of providing a cosmetic, care, or therapeutic effect.","By “cosmetic agent,” it is meant any ingredient that is appropriate for cosmetically treating, providing nutrients to, and/or conditioning the hair, nail, and/or skin via topical application.","By “pharmaceutical agent,” it is mean any drug that is either hydrophobic or hydrophilic in nature and appropriate for topical use.","As used herein “medicament agents” include those agents capable of promoting recovery from injury and illness.","As used herein “pharmaceutically, dermatologically, or cosmetically acceptable” means that the ingredients which the term describes are suitable for use in contact with the skin without undue toxicity, incompatibility, instability, irritation, allergic response, and the like.","Other than where otherwise indicated, or where required to distinguish over the prior art, all numbers expressing quantities of ingredients herein are to be understood as modified in all instances by the term “about”.","As used herein, the words “may” and “may be” are to be interpreted in an open-ended, non-restrictive manner.","At minimum, “may” and “may be” are to be interpreted as definitively including, but not limited to, the composition, structure, or act recited.","As used herein, and in particular as used herein to define the elements of the claims that follow, the articles “a” and “an” are synonymous and used interchangeably with “at least one” or “one or more,” disclosing or encompassing both the singular and the plural, unless specifically defined herein otherwise.","The conjunction “or” is used herein in both in the conjunctive and disjunctive sense, such that phrases or terms conjoined by “or” disclose or encompass each phrase or term alone as well as any combination so conjoined, unless specifically defined herein otherwise.","The description of a group or class of materials as suitable or preferred for a given purpose in connection with the invention implies that mixtures of any two or more of the members of the group or class are equally suitable or preferred.","Description of constituents in chemical terms refers unless otherwise indicated, to the constituents at the time of addition to any combination specified in the description, and does not necessarily preclude chemical interactions among the constituents of a mixture once mixed.","Steps in any method disclosed or claimed need not be performed in the order recited, except as otherwise specifically disclosed or claimed.","Changes in form and substitution of equivalents are contemplated as circumstances may suggest or render expedient.","Although specific terms have been employed herein, such terms are intended in a descriptive sense and not for purposes of limitation.","Methods of Treatment The general form of treatment for dermatoses according to the invention is chemical therapy by topical administration of the benefit agent or agents.","Topical medications may be delivered to the affected site by means including but not limited to baths, soaps, shampoos, wet dressings or soaks, powders, pastes, tinctures, shake lotions, aerosols, foams, medicated tape, transdermal devices, creams, ointments, oils, and emulsions.","Generally, the composition is topically applied to the affected skin areas in a predetermined or as-needed regimen to bring about improvement, it generally being the case that gradual improvement is noted with each successive application.","Insofar as has been determined based upon studies to date, no adverse side effects are encountered.","In treating atopic dermatitis, psoriasis, eczema, or any of the conditions or indications disclosed herein, an ointment or lotion according to aspects of the invention containing 0.01% to 10% by weight of the imidazole compound and, optionally, 0.01% to 25% of colloidal oatmeal is applied to the affected area of the skin.",".","The upper limit of the imidazole compound may preferably be 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2.5%, 2%, or even 1.5% by weight of the ointment or lotion, and the lower limit of the imidazole compound may preferably be 0.01%, 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, or even 0.5% by weight of the ointment or lotion.","Preferably the ointment or lotion comprises 1.0% by weight of the imidazole compound.","The upper limit of the colloidal oatmeal may preferably be 25%, 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2.5%, 2%, or even 1.5% by weight of the ointment or lotion, and the lower limit of the colloidal oatmeal may preferably be 0.01%, 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, or even 0.5% by weight of the ointment or lotion.","Preferably the ointment or lotion comprises 1.0% by weight of the colloidal oatmeal.","The patient may be treated, for example, daily for two to four weeks with a dosage amount of 5 mg to 10 mg of imidazole compound and 5 mg to 10 mg of colloidal oatmeal a day.","The topically effective amounts of imidazole compound are typically 0.5% to 2% by weight and of the colloidal oatmeal 0.5%% to 2% by weight in an ointment or lotion and are applied one to three times a day for a period of time, typically weeks, to effectively treat the dermatoses.","Under certain circumstances, it is desirable to administer the imidazole compound and colloidal oatmeal simultaneously with other dermatologically active agents.","The precise amount of imidazole compound and colloidal oatmeal used alone or with other dermatologic agents varies depending, for example, on the condition for which the composition is administered.","The amount, route of administration and dosing schedule will depend upon factors such as the specific indication to be treated, prevented, or managed, and the age, sex and condition of the patient.","The roles played by such factors are well known in the art, and may be accommodated by routine experimentation.","One skilled in the art can adjust the dosage forms to achieve the desired therapeutic levels.","Depending on the specific tissue to be treated, additional components may be used prior to, in conjunction with, or subsequent to treatment with active ingredients of the invention.","For example, penetration enhancers may be used to assist in delivering active ingredients to the tissue.","Another embodiment of the present invention is directed to a method for depositing a benefit agent onto the skin to a desired location on a human or animal.","While the frequency and amount of the benefit agent-containing composition to be applied will depend upon, for example, the type and amount of benefit agent available, the intended usage of the final composition, i.e.","therapeutic versus maintenance regimen, and the sensitivity of the individual user to the composition, typically the benefit agent-containing composition of the present invention should be topically applied to affected body parts at regular intervals, and preferably twice daily, in the morning and evening.","The composition may be applied more frequently during the initial stages of treatment, until the desired effect is achieved, then less frequently when maintenance is desired.","Conditions Treated The methods according to the invention can be used to treat a variety of skin conditions, which result in inflammation or erythema.","For example, inflammation or erythema can result from external causes such as sun or wind burn or irritating soaps or cleansers.","It is also known that inflammation and erythema can be caused from inherent conditions such as rosacea, atopic dermatitis, or allergic skin reactions.","The method according to the invention can be used to treat inflammation and/or erythema caused by both external and inherent conditions.","Another aspect of the invention relates to combinations of imidazole-based compounds and colloidal oatmeal and to methods of their use for the treatment, prevention, and management of atopic dermatitis, seborrheic dermatitis, contact dermatitis, cutaneous sarcoidosis, drug induced photosensitivity, fixed drug eruptions, id reactions, bullous skin diseases, discoid lupus erythematosus, subacute cutaneous lupus, alopecia areata, sea bathers eruptions, psoriasis, dyshidrotic eczema, and Pompholyx.","This list of examples of dermatological conditions, for which the therapy as proposed in this application is useful, does not limit the present invention to these indications, since there may be other dermatological conditions not mentioned here where combinations of imidazole-based compounds and colloidal oatmeal may also be effective.","Thus, further non-limiting examples of conditions to which the present invention may be applied include: (a) dermatologic allergies, such as contact dermatitis, photoallergic dermatitis; industrial dermatoses caused by exposure to a variety of compounds used by industry that are contact irritants; atopic eczema (infantile and adult), dermatoses caused by drugs and nummular eczema; (b) immune-mediated skin diseases, suchbullous pemphigoid, pemphigus vulgaris, necrotizing vasculitis, lupus erythematosus (discoid and systemic), dermatitis herpetiformis; (B2) immune, non-immune, or autoimmune urticarias such as allergic urticaria, chronic idiopathic urticaria, solar urticaria, cholinergic urticaria, pressure urticaria, cold urticaria, dermatographia, and pruritic urticarial papules and plaques of pregnancy (PUPPP); (B3) mastocytosis; (c) pruritic dermatoses, such as winter, senile, and essential pruritus, pruritus ani, external otitis, and genital pruritus; (d) vascular dermatoses, such as erythema multiforme, erythema nodosum, stasis dermatitis, purpuric dermatoses such as thrombocytopenic purpura and Henoch-Schonlein purpura, ecchymoses, stasis purpura, primary and secondary telangiectases; (e) seborrheic dermatitis, acne, and rosacea; (f) papulosquamous dermatoses: such as psoriasis, pityriasis rosea, lichen planus; (g) bacterial dermatoses, such as pyoderma, impetigo, ecthyma, folliculitis, furuncles styes, carbuncles, sweat gland infections, erysipelas, erythrasma, infected ulcers, and infected eczematoid dermatitis; (h) systemic bacterial infections with skin manifestations, such as scarlet fever, granuloma inguinale, chancroid, tuberculosis, leprosy, gonorrhea, rickettsial diseases, actinomycosis, syphilis; (i) viral skin infection, such as those caused by herpes simplex virus, Kaposi's varicelliform eruption, zoster, chickenpox, smallpox, vaccinia, cowpox, warts, molluscum contagiosum, lymphogranuloma venereum, exanthematous diseases such as German measles, roseola and erythema infectiosum; (j) mycolic skin infections, such as tinea (superficial fungal infections of the skin in various body sites), sporotrichosis, North American blastomycosis; (k) granulomatous dermatoses, such as sarcoidosis, granuloma annulare, silica induced granulomas; (1) parasitic skin infections, such as scabies, pediculosis; (m) bullous dermatoses; (n) exfoliative dermatitis, primary and secondary; (o) pigmented dermatoses, such as chloasma (melasma) and vitiligo; (p) collagen diseases, such as lupus erythematosus, scleroderma, dermatomyositis; (q) dermatoses due to internal diseases, such as Kaposi's sarcoma, pyoderma gangrenosum associated with ulcerative colitis, ulcers due to diabetes, xanthomas; (r) diseases of mucous membranes, such as aphthous ulcers; (s) dermatoses due to physical agents, such as sunburns and radiation; and (t) photosensitive dermatoses of the exogenous-type, such as drug-induced photodermatitis, contact dermatitis with photoallergic components, and of the endogenous-type, such as porphyrias, collagen vascular disorders such as lupus erythematosus, dermatomyositis, and polymorphous light eruptions.","Contact dermatitis is a steroid responsive condition and is caused by plant saps (poison ivy, etc) and chemicals.","About 80% are irritant type while 20% are allergic.","There are over 85,000 chemicals estimated to exist in the modern environment.","Any might cause contact dermatitis.","The most common allergic sensitizers are nickel sulfate, fragrances, thimerosal, quartemium-15, neomycin sulfate, formaldehyde, bacitracin, thiuram mix, balsam of Peru, cobalt chloride, p-phenylenediamine, and carba mix.","Other steroid responsive dematoses might include seborrheic dermatitis, diaper rash, and bullous skin diseases such as bullous pemphigoid.","Further examples of diseases and disorders include ankylosing spondylitis, asthma (e.g., bronchial asthma), atopic dermatitis, Behcet's disease, graft-vs-host disease, Kawasaki syndrome, lupus erythematosus, multiple sclerosis, myasthenia gravis, pollinosis, psoriasis, psoriatic arthritis, rheumatoid arthritis, scleroderma, transplant rejection (e.g., of organ, cell or bone marrow), type 1 diabetes, and uveitis.","Additional diseases and disorders include Addison's Disease, anti-phospholipid syndrome, autoimmune atrophic gastritis, achlorhydra autoimmune, Celiac Disease, Crohn's Disease, Cushing's Syndrome, dermatomyositis, Goodpasture's Syndrome, Grave's Disease, Hashimoto's thyroiditis, idiopathic adrenal atrophy, idiopathic thrombocytopenia, Lambert-Eaton Syndrome, pemphigoid, pemphigus vulgaris, pernicious anemia, polyarteritis nodosa, primary biliary cirrhosis, primary sclerosing cholangitis, Raynauds, Reiter's Syndrome, relapsing polychondritis, Schmidt's Syndrome, Sjogren's Syndrome, sympathetic ophthalmia, Takayasu's Arteritis, temporal arteritis, thyrotoxicosis, ulcerative colitis, and Wegener's granulomatosis.","Further indications addressed by the compositions and methods of the invention include, for example, immunosuppression (e.g., employing one or more agents such as cyclosporin A, QKT3, FK506, mycophenolate mofetil (MMF), azathioprine, corticosteroids (such as prednisone), antilymphocyte globulin, antithymocyte globulin, and the like), inflammatory disease therapy (e.g., employing disease-modifying agents (such as antimalarials, methotrexate, sulfasalazine, mesalamine, azathioprine, 6-mercaptopurine, metronidazole, injectable and oral gold, D-penicillamine, and the like), corticosteroids, non-steroidal antiinflammatory drugs (such as aspirin, sodium salicylate, magnesium salicylate, choline magnesium salicylate, salicylsalicylic acid, ibuprofen, naproxen, diclofenac, diflunisal, etodolac, fenoprofen calcium, fluriprofen, piroxicam, indomethacin, ketoprofen, ketorolac tromethamine, meclofenamate, meclofenamate sodium, mefenamic acid, nabumetone, oxaprozin, phenyl butyl nitrone (PBN), sulindac, tolmetin, and the like), and the like), anti-cancer therapy (e.g., employing one or more agents such as alkylating agents (such as mechlorethamine, chlorambuccil, ifosfamide, melphalan, busulfan, carmustine, lomustine, procarbazine, dacarbazine, cisplatin, carboplatin, and the like), antimetabolites (such as methotrexate, mercaptopurine, thioguanine fluorouracil, cytarabine, and the like), hormonal agents (such as testosterone propionate, fluoxymesterone, flutamide, diethylstilbestrol, ethinyl estradiol, tamoxifen, hydroxyprogesterone caproate, medroxyprogesterone, megestrol acetate, and the like), adrenocorticosteroids (such as prednisone), aromatase inhibitors (such as amino glutethimide), leuprolide, goserelin acetate, biological response modifiers (such as interferon-.alpha.2a, interferon-.alpha.2b, interleukin-2, and the like), peptide hormone inhibitors (such as octreotide acetate), natural products (such as vinblastine, vincristine, vinorelbine, paclitaxel, dactinomycin, daunorubicin, idarubicin, doxorubicin, etoposide, plicamycin, mitomycin, mitoxantrone, bleomycin, hydroxyurea, mitotane, fludarabine, cladribine, and the like), supportive agents (such as allopurinol, mesna, leucovorin, erythropoietin, filgrastim, sargramostim, and the like), and the like, anti-microbial therapy (e.g., employing one or more agents such as celftriaxone, TMP-SMZ, penicillin, aminoglycosides, vancomycin, gentamicin, rifampin, imipenem, clindamycin, metronidazole, tetracycline, erythromycin, sulfonamide, streptomycin, ampicillin, isoniazid, pyrazinamide, ethambutol, and the like), anti-fungal therapy (e.g., employing agents such as amphotericin B, griseofulvin, myastatin, flucytosine, natamycin, antifungal imidazoles (e.g., clotrimazole, miconazole, ketoconazole, fluconazole, itraconazole, and the like), and the like, anti-retroviral therapy (e.g., employing agents such as protease inhibitors (such as Invirase, Ritonavir, Crixivan, and the like), zidovudine, didanosine, zalcitabine, stavudine, viramune, and the like), and treatment of cellular proliferative diseases (e.g., oncolytic viral therapy employing naturally occurring and/or modified oncolytic viruses such as reovirus, adenovirus, seneca valley virus, vesicular stomatitis virus, poliovirus, vacina virus, herpes virus and the like), and treatment of opportunistic infections and malignancies (e.g., anti-AIDS treatment, employing agents such as pentamidine, trimethoprim/sulfamethoxazole, primaquine, atovaquope, clarithromycin, clofazimine, ethambutol, rifampin, amikacin, ciprofloxacin, pyrimethamine, amphotericin B, ganciclovir, foscarnet, fluconazole, ketoconazole, acyclovir, and the like).","Benefit Agents A first element of the compositions and methods according to aspects of the invention is an imidazole compound of the formula: wherein: R1is hydrogen, alkyl or aryl; R6 is OR10 or OC(O)R11; R7 is ORH or OC(O)R11; R8 is OR12 or OC(O)R12; and R9 is hydrogen, CH2OR13 or CH2OC(O)R13; and each of R10, R11, R12 and R13 is independently hydrogen or lower alkyl.","The compounds of the preceding formula of the present invention may also be present in the form of pharmaceutically, dermatologically, or cosmetically acceptable salts thereof that can be made by conventional techniques.","Pharmaceutically, dermatologically, or cosmetically acceptable acidic/anionic salts include, and are not limited to acetate, benzenesulfonate, benzoate, bicarbonate, bitartrate, bromide, calcium edetate, camsylate, carbonate, chloride, citrate, dihydrochloride, edetate, edisylate, estolate, esylate, fumarate, glyceptate, gluconate, glutamate, glycollylarsanilate, hexylresorcinate, hydrabamine, hydrobromide, hydrochloride, hydroxynaphthoate, iodide, isethionate, lactate, lactobionate, malate, maleate, mandelate, mesylate, methylbromide, methylnitrate, methylsulfate, mucate, napsylate, nitrate, pamoate, pantothenate, phosphate/diphospate, polygalacturonate, salicylate, stearate, subacetate, succinate, sulfate, tannate, tartrate, teoclate, tosylate and triethiodide.","Pharmaceutically, dermatologically, or cosmetically acceptable basic/cationic salts include, and are not limited to aluminum, benzathine, calcium, chloroprocaine, choline, diethanolamine, ethylenediamine, lithium, magnesium, meglumine, potassium, procaine, sodium and zinc.","Other salts may, however, be useful in the preparation of compounds according to this invention or of their cosmetically acceptable salts.","Organic or inorganic acids also include, and are not limited to, hydriodic, perchloric, sulfuric, phosphoric, propionic, glycolic, methanesulfonic, hydroxyethanesulfonic, oxalic, 2-naphthalenesulfonic, p-toluenesulfonic, cyclohexanesulfamic, saccharinic or trifluoroacetic acid.","In particular embodiments, the imidazole compound is 2-acetyl-4-tetrahydroxybutylimidazole (THI).","THI is a component of caramel color III and has been identified as a sphingosine-1-phosphate lyase antagonist.","Sphingosine-1-phosphate (SIP) is a bioactive molecule with effects on multiple organ systems.","Sphingosine-1-phosphate lyase is a vitamin B6-dependent enzyme localized in the membrane of the endoplasmic reticulum.","Van Veldhoven and Mannaerts, J. Biol.","Chem.","266:12502-12507 (1991); Van Veldhoven and Mannaerts, Adv.","Lipid.","Res.","26:69 (1993).","The polynucleotide and amino acid sequences of human SP1 lyase and its gene products are described in PCT Patent Application No.","WO 99/16888.THI inhibits S1P lyase activity when administered to mice.","Schwab, S. et al., Science 309:1735-1739 (2005).","Administration of the compound to rats and mice induces lymphopenia and causes the accumulation of mature T cells in the thymus.","See, e.g., Schwab, supra; Pyne, S. G., ACGC Chem.","Res.","Comm.","11:108-112 (2000); Gugasyan, R., et al., Immunology 93(3):398-404 (1998); Halweg, K. M. and Büchi, G., J. Org.","Chem.","50:1134-1136 (1985); U.S. Pat.","No.","4,567,194 to Kroeplien and Rosdorfer.","Still, there are no known reports of THI having an immunological effect in animals other than mice and rats.","Although U.S. Pat.","No.","4,567,194 alleges that THI and some related compounds may be useful as immunosuppressive medicinal agents, studies of the compound in humans have found no immunological effects.","See Thuvander, A. and Oskarsson, A., Fd.","Chem.","Toxic.","32(1):7-13 (1994); Houben, G. F., et al., Fd.","Chem.","Toxic.","30(9):749-757 (1992).","Compounds of the invention may contain one or more stereocenters, and can exist as racemic mixtures of enantiomers or mixtures of diastereomers.","This invention encompasses stereomerically pure forms of such compounds, as well as mixtures of those forms.","Stereoisomers may be asymmetrically synthesized or resolved using standard techniques such as chiral columns or chiral resolving agents.","See, e.g., Jacques, J., et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Wilen, S. H., et al., Tetrahedron 33:2725 (1977); Eliel, E. L., Stereochemistry of Carbon Compounds (McGraw Hill, NY, 1962); and Wilen, S. H., Tables of Resolving Agents and Optical Resolutions, p. 268 (E. L. Eliel, Ed., Univ.","of Notre Dame Press, Notre Dame, Ind., 1972).","This invention further encompasses stereoisomeric mixtures of compounds disclosed herein.","It also encompasses configurational isomers of compounds disclosed herein, either in admixture or in pure or substantially pure form.","Compounds of the invention can be prepared by methods known in the art (e.g., by varying and adding to the approaches described in Pyne, S. G., ACGC Chem.","Res.","Comm.","11:108-112 (2000); Halweg, K. M. and Büchi, G., J. Org.","Chem.","50:1134-1136 (1985)).","Compounds can also be made by the methods disclosed below and variants thereof, which will be apparent to those of ordinary skill in the art.","The compositions according to the invention preferably contain the imidazole-based compound in an amount of 0.001% to 10%, more preferably 0.5% to 2%, and most preferably about 1% by weight of the composition.","The imidazole-based compound may also preferably be included in an amount of 0.01% to 10%, 0.1% to 10%, 0.1% to 9%, 0.1% to 8%, 0.1% to 7%, 0.1% to 6%, 0.1% to 5%, 0.2% to 5%, 0.3% to 5%, 0.4% to 5%, 0.5% to 5%, 0.5% to 4%, and 0.5% to 3% by weight of the composition.","A further element of preferred compositions and methods according to aspects of the invention is colloidal oatmeal.","Oatmeal has been used as a soothing agent to relieve itch and irritation associated with various xerotic dermatoses.","In 1945, a ready to use colloidal oatmeal, produced by finely grinding the oat and boiling it to extract the colloidal material, became available.","Today, colloidal oatmeal is available in various dosage forms from powders for the bath to shampoos, shaving gels, and moisturizing creams.","Currently, the use of colloidal oatmeal as a skin protectant is regulated by the U.S. Food and Drug Administration (FDA) according to the Over-The-Counter Final Monograph for Skin Protectant Drug Products issued in June 2003.Its preparation is also standardized by the United States Pharmacopeia.","The many clinical properties of colloidal oatmeal derive from its chemical polymorphism.","The high concentration in starches and beta-glucan is responsible for the protective and water-holding functions of oat.","The presence of different types of phenols confers antioxidant and anti-inflammatory activity.","Some of the oat phenols are also strong ultraviolet absorbers.","The cleansing activity of oat is mostly due to saponins.","Its many functional properties make colloidal oatmeal a cleanser, moisturizer, buffer, as well as a soothing and protective anti-inflammatory agent.","Colloidal oatmeal may act at the site of application to control the osmotic pressure of water with respect to the skin and permits adequate water to enter into the stratum corneum.","Oatmeal may leave an occlusive film on the skin that serves to hold in moisture, which protects the skin against irritation and acts as an antipruritic.","Colloidal oatmeal includes the powder resulting from the grinding and further processing of whole oat grain meeting United States Standards for Number 1 or Number 2 oats.","A suitable colloidal oatmeal has a particle size distribution as follows: not more than 3 percent of the total particles exceed 150 micrometers in size and not more than 20 percent of the total particles exceed 75 micrometers in size.","Examples of suitable colloidal oatmeals include, but are not limited to, “Tech-O” colloidal oatmeals (e.g., Tech-O #11-065 colloidal oatmeal) available from the Beacon Corporation and colloidal oatmeals available from Quaker.","A USP grade of colloidal oatmeal suitable for use in this invention may be obtained under the mark “Tech-O” from Beacon CMP Corporation, 611 Springfield Road, Kenilworth, N.J. 07033.The compositions may further contain one or more benefit agents or pharmaceutically-acceptable salts thereof.","The benefit agents useful herein may be categorized by their therapeutic benefit or their postulated mode of action.","However, it is to be understood that the benefit agents useful herein may, in some circumstances, provide more than one therapeutic benefit or operate via greater than one mode of action.","Therefore, the particular classifications provided herein are made for the sake of convenience and are not intended to limit the benefit agents to the particular application(s) listed.","In addition, the compounds, which are identified below as being suitable for use as benefit agents, may be used in an amount over and above the amount that they may be used for other purposes in the compositions of the invention.","Further benefit agents useful in the methods and compositions of the invention include antipruritics, emollients, antiseptics, antifungals, antiinflammatories, immunosuppressants, psoriasis agents, anti-cancer agents, antibiotics, antiparasitics, antioxidants, antibacterials, antimicrobials, antiretrovirals, moisturizers, sunscreens, NSAIDs, hormones, steroids, analgesics, antihistamines, and antipyretics.","The following chemotherapeutic agents used to treat dermatoses are not comprehensive but rather consist of examples of commonly used groups of drugs.","The antihistamines added to the topical compositions are typically from the structural classes of ethylenediamines, aminoalkylethers, and alkylamines.","Among the ethylenediamine group are such antihistamines as antazoline phosphate, clemizole hydrochloride, chlorcyclizine hydrochloride, chlorothen, methapheniline hydrochloride, dorastine hydrochloride, methdilazine hydrochloride, promethazine hydrochloride, pyrathiazine hydrochloride, pyrilamine maleate, quinetolate, thenaldine, thenyldiamine hydrochloride, thonzylamine hydrochloride, tripelennamine, and zolamine hydrochloride.","Among the aminoalkylether group are such antihistamines as chlorphenoxamine hydrochloride, carbinoxamine maleate, clemastine, diphenhydramine hydrochloride, diphenylpyraline hydrochloride, doxylamine succinate, and pyroxamine maleate.","Among the alkamine group are such antihistamines as azatadine maleate, bromdiphenhydramine hydrochloride, cyproheptadine hydrochloride, dimethindene maleate, phenindamine tartrate, pheniramine maleate, brompheniramine maleate, dexbrompheniramine maleate, chlorpheniramine maleate, dex-chlorpheniramine maleate, closiramine, cycliramine maleate, mianserin hydrochloride, pyrrobutamine phosphate, terfenadine, and triprolidine hydrochloride.","Besides the above, some compositions in structural groups, which groups are not primarily antihistamines such as phenothiazines, piperidines, and piperazines, have antihistaminic characteristics.","These groups include promethazine, astemizole, fexofenadine, loratadine, desloratadine, terfenadine, cetirizine, and meclizin, which are antihistaminic.","Another active ingredient used in the formulations hereof is the employment of a topical anesthetic.","While some of these topical anesthetic compounds are structurally related to the antihistamines in the preceding paragraph, the compounds take on a disinct role in preparations described.","The first group are esters of benzoic acid and diethylaminoethyl alcohols, namely, benzocaine, chloroprocaine, procaine, and tetracaine.","Other synthetic anesthetic compounds, which are not esters of benzoic acid and are pharmacologically grouped together, are bupivacaine, dibucaine, lidocaine, mepivacaine, and prilocaine.","Besides these two groups, the compounds of etidocaine and pramoxine are also applicable.","In one of the topical spray formulations described below the anesthetic, pramoxine hydrochloride, comprises up to 1.0 percent by weight thereof.","Corticosteroids are a group of agents used to treat inflammation of the skin having many different etiologies.","Examples of indications in which systemically administered corticosteroids are employed as therapeutics include psoriasis, erythema nodosum leprosum, discold lupus erythematosus, urticaria, different types of pruritis, pemphigus and keloids.","Antihistamines are a group of agents having an antipruritic effect.","They include alkylamines, phenothiazines, ethylenediamine, ethanolamine, and piperazine.","Retinoids are synthetic and natural forms of vitamin A, including isotretinoin and etretinate.","Retinoids are used to treat acne vulgaris or rosacea and psoriasis.","Antimicrobial compounds include antibiotic, antibacterial, antifungal, antiviral, and antiparasitic agents.","In addition to the imidazole-based compound and colloidal oatmeal, the benefit agents comprising topical preparations used according to the invention may also comprise: (a) anti pruritic agents, which relieve itching, such as 0.25% menthol, 0.5% phenol, 2% camphor and 2-10% coal tar solutions; (b) keratoplastic agents, which increase the thickness of the horny layer of the skin, such as 1-2% salicylic acid; (c) emollients, which often soften surface layers of skin, such as petrolatum, nivea oil and mineral oil; (d) antiseptics, which inhibit and/or destroy fungi and/or bacteria, such as 3% Vioform, 3-10% ammoniated mercury, antifungal agents such as Whitfields ointment, antibiotics such as 3% terramycin, 0.5% neomycin, 0.1% garamycin and 3% aureomycin; (e) antieczematous agents, which remove oozing and vesicular excretions, such as Burows solution, soaks or packs, 2-5% coal tar solutions and 0.5-2% hydrocortisone; (f) keratolytic agents, which remove or soften the horny layer of the skin, such as 4-10% salicylic acid, 2-4% resorcinol and 4-10% sulfur; and (g) antiparasitics, which inhibit or destroy infestations by parasites, such as Kewell cream for scabies and pediculosis and Eurax lotion for scabies.","Further examples of suitable benefit agents include, but are not limited to: depigmentation agents; reflectants; film forming polymers; humectants; amino acids and their derivatives; antimicrobial agents; allergy inhibitors; anti-acne agents; anti-aging agents; anti-wrinkling agents, antiseptics; analgesics; antitussives; antipruritics; local anesthetics; anti-hair loss agents; hair growth promoting agents; hair growth inhibitor agents, antihistamines such as Mandragora Vernalis, Tanacetum Parthenium and the like; antiinfectives such as Acacia Catechu, Aloe Barbadensis, Convallaria Maj alis, Echinacea, Eucalyptus, Mentha Piperita, Rosa Canina, Sassafras Albidum, and the like; inflammation inhibitors; anti-emetics; anticholinergics; vasoconstrictors; vasodilators; wound healing promoters; peptides, polypeptides and proteins; deodorants and anti-perspirants; medicament agents; skin emollients and skin moisturizers; skin firming agents, hair conditioners; hair softeners; hair moisturizers; vitamins; tanning agents; skin lightening agents; antifungals such as Centaurea Cyanus, Kalmia Latifolia and antifungals for foot preparations; depilating agents; shaving preparations; external analgesics; perfumes; counterirritants; hemorrhoidals; insecticides; poison ivy products; poison oak products; burn products; anti-diaper rash agents; prickly heat agents; make-up preparations; vitamins; amino acids and their derivatives; herbal extracts; retinoids; flavenoids; sensates; anti-oxidants; skin conditioners; hair tighteners; chelating agents; cell turnover enhancers; coloring agents; pigments; sunscreens; anti-edema agents; collagen enhancers; and mixtures thereof.","Examples of suitable anti-edema agents nonexclusively include bisabolol natural, synthetic bisabolol, and mixtures thereof.","Examples of suitable vasoconstrictors nonexclusively include horse chestnut extract, prickly ash, and mixtures thereof.","Examples of suitable anti-inflammatory agents nonexclusively include benoxaprofen, centella asiatica, bisabolol, feverfew (whole), feverfew (parthenolide free), green tea extract, green tea concentrate, hydrogen peroxide, lycopene including “Lyc-o-Pen” available from LycoRed Natural Products Industries, Ltd., oat oil, chamomile, and mixtures thereof.","Examples of collagen enhancers nonexclusively include vitamin A, vitamin C, and mixtures thereof.","Examples of suitable skin firming agent nonexclusively include dimethylaminoethanol (“DMAE”).","Examples of suitable antipruritics and skin protectants nonexclusively include betaglucan, feverfew, soy and derivatives thereof, bicarbonate of soda, colloidal oatmeal, surfactant based colloidal oatmeal cleanser, Anagallis Arvensis, Oenothera Biennis, Verbena Officinalis, and the like.","Examples of suitable reflectants nonexclusively include mica, alumina, calcium silicate, glycol dioleate, glycol distearate, silica, sodium magnesium fluorosilicate, and mixtures thereof.","Suitable film forming polymers include those that, upon drying, produce a substantially continuous coating or film on the skin.","Nonexclusive examples of suitable film forming polymers include acrylamidopropyl trimonium chloride/acrylamide copolymer; corn starch/acrylamide/sodium acrylate copolymer; polyquatemium-10; polyquaternium-47; polyvinylmethylether/maleic anhydride copolymer; styrene/acrylates copolymers; and mixtures thereof.","Commercially available humectants which are capable of providing moisturization and conditioning properties to the composition are suitable for use in the present invention.","Examples of suitable humectants nonexclusively include: water soluble liquid polyols selected from the group comprising glycerine, propylene glycol, hexylene glycol, butylene glycol, pentylene glycol, dipropylene glycol, and mixtures thereof; polyalkylene glycols; polyethylene glycol ether of methyl glucose; urea; fructose; glucose; honey; lactic acid; maltose; sodium glucuronate; and mixtures thereof.","Suitable amino acid agents include amino acids derived from the hydrolysis of various proteins as well as the salts, esters, and acyl derivatives thereof.","Examples of such amino acid agents nonexclusively include amphoteric amino acids such as alkylamido alkylamines, i.e.","stearyl acetyl glutamate, capryloyl silk amino acid, capryloyl collagen amino acids; capryloyl keratin amino acids; capryloyl pea amino acids; cocodimonium hydroxypropyl silk amino acids; corn gluten amino acids; cysteine; glutamic acid; glycine; hair keratin amino acids; amino acids such as aspartic acid, threonine, serine, glutamic acid, proline, glycine, alanine, cystine, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, cysteic acid, lysine, histidine, arginine, cysteine, tryptophan, citrulline; lysine; silk amino acids, wheat amino acids; and mixtures thereof.","Suitable proteins include those polymers that have a long chain, i.e.","at least about 10 carbon atoms, and a high molecular weight, i.e.","at least about 1000, and are formed by self-condensation of amino acids.","Nonexclusive examples of such proteins include collagen, deoxyribonuclease, iodized corn protein; milk protein; protease; serum protein; silk; sweet almond protein; wheat germ protein; wheat protein; alpha and beta helix of keratin proteins; hair proteins, such as intermediate filament proteins, high-sulfur proteins, ultrahigh-sulfur proteins, intermediate filament-associated proteins, high-tyrosine proteins, high-glycine tyrosine proteins, tricohyalin, and mixtures thereof.","Examples of suitable vitamins nonexclusively include vitamin B complex; including thiamine, nicotinic acid, biotin, pantothenic acid, choline, riboflavin, vitamin B6, vitamin B12, pyridoxine, inositol, carnitine; vitamins A, C, D, E, K and their derivatives such as vitamin A palmitate and pro-vitamins, e.g.","(i.e.","panthenol (pro vitamin B5) and panthenol triacetate) and mixtures thereof.","Examples of suitable antibacterial agents nonexclusively include bacitracin, erythromycin, neomycin, tetracycline, chlortetracycline, benzethonium chloride, phenol, and mixtures thereof.","Examples of suitable skin emollients and skin moisturizers nonexclusively include mineral oil, lanolin, vegetable oils, isostearyl isostearate, glyceryl laurate, methyl gluceth-10, methyl gluceth-20 chitosan, and mixtures thereof.","Examples of sunscreen agents nonexclusively include benzophenones, bornelone, butyl paba, cinnamidopropyl trimethyl ammonium chloride, disodium distyrylbiphenyl disulfonate, paba, potassium methoxycinnamate, butyl methoxydibenzoylmethane, octyl methoxycinnamate, oxybenzone, octocrylene, octyl salicylate, phenylbenzimidazole sulfonic acid, ethyl hydroxypropyl aminobenzoate, menthyl anthranilate, aminobenzoic acid, cinoxate, diethanolamine methoxycinnamate, glyceryl aminobenzoate, titanium dioxide, zinc oxide, oxybenzone, Padimate O, red petrolatum, and mixtures thereof.","Further examples of sunscreen active agents include, but are not limited to octyl methoxycinnamate (ethylhexyl p-methoxycinnamate), octyl salicylate oxybenzone (benzophenone-3), benzophenone-4, menthyl anthranilate, dioxybenzone, aminobenzoic acid, amyl dimethyl PABA, diethanolamine p-methoxy cinnamate, ethyl 4-bis (hydroxypropyl) aminobenzoate, 2-ethylhexy 1-2-cyano-3,3-diphenylacrylate, homomenthyl salicylate, glyceryl aminobenzoate, dihydroxyacetone, octyl dimethyl PABA, 2-phenylbenzimidazole-5-sulfonic acid, triethanolamine salicylate, zinc oxide, and titanium oxide, and mixtures thereof.","Examples of suitable anti-aging agents include, but are not limited to inorganic sunscreens such as titanium dioxide and zinc oxide; organic sunscreens such as octyl-methoxy cinnamates and derivatives thereof; retinoids; vitamins such as vitamin E, vitamin A, vitamin C, vitamin B, and derivatives thereof such as vitamin E acetate, vitamin C palmitate, and the like; antioxidants including beta carotene, alpha hydroxy acids such as glycolic acid, citric acid, lactic acid, malic acid, mandelic acid, ascorbic acid, alpha-hydroxybutyric acid, alpha-hydroxyisobutyric acid, alpha-hydroxyisocaproic acid, atrrolactic acid, alpha-hydroxyisovaleric acid, ethyl pyruvate, galacturonic acid, glucoheptonic acid, glucoheptono 1,4-lactone, gluconic acid, gluconolactone, glucuronic acid, glucuronolactone, glycolic acid, isopropyl pyruvate, methyl pyruvate, mucic acid, pyruvic acid, saccharic acid, saccaric acid 1,4-lactone, tartaric acid, and tartronic acid; beta hydroxy acids such as beta-hydroxybutyric acid, beta-phenyl-lactic acid, beta-phenylpyruvic acid; botanical extracts such as green tea, soy, milk thistle, algae, aloe, angelica, bitter orange, coffee, goldthread, grapefruit, hoellen, honeysuckle, Job's tears, lithospermum, mulberry, peony, puerarua, nice, safflower, and mixtures thereof.","Examples of suitable external analgesics and local anesthetics nonexclusively include benzocaine, dibucaine, benzyl alcohol, camphor, capsaicin, capsicum, capsicum oleoresin, juniper tar, menthol, methyl nicotinate, methyl salicylate, phenol, resorcinol, turpentine oil, and mixtures thereof.","Examples of suitable antiperspirants and deodorants nonexclusively include aluminium chlorohydrates, aluminium zirconium chlorohydrates, and mixtures thereof.","Examples of suitable counterirritants nonexclusively include camphor, menthol, methyl salicylate, peppermint and clove oils, ichtammol, and mixtures thereof Examples of suitable inflammation inhibitors nonexclusively includes hydrocortisone, Fragaria Vesca, Matricaria Chamomilla, and Salvia Officinalis.","Other well-known antipruritic agents include phenol, camphor, menthol, hydro-cortisone, hydrocortisone acetate, camphorated metacresol, phenolated sodium, and mixtures thereof.","Other preferred benefit agents nonexclusively include DMAE, soy and derivatives thereof, colloidal oatmeal, sulfonated shale oil, olive leaf, elubiol, 6-(1-piperidinyl)-2,4-pyrimidinediamine-3-oxide, finasteride, ketoconazole, salicylic acid, zinc pyrithione, coal tar, benzoyl peroxide, selenium sulfide, hydrocortisone, sulfur, menthol, pramoxine hydrochloride, tricetylmonium chloride, polyquaternium 10, panthenol, panthenol triacetate, vitamin A and derivatives thereof, vitamin B and derivatives thereof, vitamin C and derivatives thereof, vitamin D and derivatives thereof, vitamin E and derivatives thereof, vitamin K and derivatives thereof, keratin, lysine, arginine, hydrolyzed wheat proteins, hydrolyzed silk proteins, octyl methoxycinnamate, oxybenzone, minoxidil, titanium dioxide, zinc dioxide, retinol, erthromycin, tretinoin, and mixtures thereof.","One preferred type of benefit agent includes those therapeutic components that are effective in the treatment of seborrheic dermatitis and psoriasis as well as the symptoms associated therewith.","Examples of such suitable benefits agents nonexclusively include zinc pyrithione, anthralin, shale oil and derivatives thereof such as sulfonated shale oil, selenium sulfide, sulfur; salicylic acid; coal tar; povidone-iodine, imidazoles such as ketoconazole, dichlorophenyl imidazolodioxalan, which is commercially available from Janssen Pharmaceutica, Nev., under the tradename, “Elubiol”, clotrimazole, itraconazole, miconazole, climbazole, tioconazole, sulconazole, butoconazole, fluconazole, miconazole nitrate and any possible stereo isomers and derivatives thereof; piroctone olamine (Octopirox); selenium sulfide; ciclopirox olamine; anti-psoriasis agents such as vitamin D analogs, e.g.","calcipotriol, calcitriol, and tacaleitrol; vitamin A analogs such as esters of vitamin A, e.g.","vitamin A palmitate, retinoids, retinols, and retinoic acid; corticosteroids such as hydrocortisone, clobetasone, butyrate, clobetasol propionate and mixtures thereof.","Further examples of benefit agents are emollients, skin conditioning agents, humectants, preservatives, antioxidants, perfumes, chelating agents, or mixtures thereof.","Emollients in the composition of the invention function have ability to remain on the skin surface or in the stratum corneum to act as lubricants, to reduce flaking, and to improve the skin appearance.","Typical emollients include fatty esters, fatty alcohols, mineral oil, polyether siloxane copolymers and the like.","Examples of suitable emollients include, but are not limited to, polypropylene glycol (“PPG”)-15 stearyl ether, PPG-10 acetyl ether, steareth-10, oleth-8, PPG-4 lauryl ether, vitamin E acetate, PEG-7 glyceryl cocoate, lanolin, cetyl alcohol, (e.g., Cetyl Alcohol NF available from Lotioncrafter LLC) octyl hydroxystearate, dimethicone (e.g., Xiameter® PMX-200 Silicone Fluid 100CS available from Dow Corning), and combinations thereof.","Examples of skin conditioning agents include, but are not limited to, olive leaf, sulfonated shale oil, elubiol, 6-(1-piperidinyl)-2,4-pyrimidinediamine-3-oxide, finasteride, ketoconazole, zinc pyrithione, coal tar, benzoyl peroxide, selenium sulfide, hydrocortisone, pramoxine hydrochloride, tricetylammonium chloride, polyquaternium 10, panthenol, panthenol triacetate, vitamin B and derivatives thereof, vitamin C and derivatives thereof, vitamin D and derivatives thereof, vitamin E and derivatives thereof, vitamin K and derivatives thereof, keratin, lysine, arginine, hydrolyzed wheat proteins, hydrolyzed silk proteins, octyl methoxycinnamate, oxybenzone, minoxidil, titanium dioxide, zinc dioxide, erthromycin, tretinoin, and mixtures thereof.","Polyhydric alcohols can be utilized as humectants in the compositions of the invention.","The humectants aid in increasing the effectiveness of the emollient, reduce scaling, stimulate removal of built-up scale and improve skin feel.","Suitable polyhydric alcohols include, but are not limited to, glycerol (also known as glycerin), polyalkylene glycols, alkylene polyols and their derivatives, including butylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, polyethylene glycol and derivatives thereof, sorbitol, hydroxypropyl sorbitol, hexylene glycol, 1,3-dibutylene glycol, 1,2,6,-hexanetriol, ethoxylated glycerol, propoxylated glycerol and mixtures thereof.","Examples of suitable preservatives for use in the compositions of the invention include the Ci-C4 alkyl parabens and phenoxyethanol (e.g., Microcare® PE available from Thor Personal Care).","Suitable antioxidants include butylated hydroxy toluene (BHT), ascorbyl palmitate, butylated hydroanisole (BHA), phenyl-[alpha]-naphthylamine, hydroquinone, propyl gallate, nordihydroquiaretic acid, vitamin E or derivatives of vitamin E, vitamin C and derivatives thereof, calcium pantothenic, green tea extracts and mixed polyphenols, and mixtures thereof.","Any fragrance may be added to the compositions of the invention for aesthetic purposes.","Suitable fragrances include, but are not limited to, eucalyptus oil, camphor synthetic, peppermint oil, clove oil, lavender, chamomile and the like.","In certain aspects of this invention, the compositions may include a chelating agent.","Chelating agents which are useful in the compositions of present invention include ethylenediamine tetra acetic acid (EDTA) and derivatives and salts thereof, dihydroxyethyl glycine, tartaric acid, and mixtures thereof.","It is also envisioned that the composition of this invention could be combined with other agents topical anesthetics, for example, such as benzocaine or other caine type molecules, or even mild steroids such as hydrocortisone for enhanced anti-inflammatory activity.","Further benefit agents useful in the compositions and methods of the present invention include, but are not limited to: antihistamine/antipruritic drugs, such as ethanolamines (e.g., diphenhydramine, diphenhydramine hydrochloride, clemastine, clemastine fumarate, and the like), ethylenediamines (e.g., brompheniramine, brompheniramine maleate, chlorpheniramine, chlorpheniramine maleate, dexchlorpheniramine maleate, triprolidine, triprolidine hydrochloride, and the like), phenothiazines (e.g., promethazine), piperidines (e.g., hydroxzine, hydroxyzine hydrochloride, terfenadine, astemizole, azatadine, azatadine maleate, and the like), cyproheptadine, cyproheptadine hydrochloride, loratidine, carbinoxamine maleate, diphenylpyraline hydrochloride, phenindamine tartrate, tripelennamine hydrochloride, methdilazine hydrochloride, trimprazine tartrate, and the like; immunosuppressants, such as glucocorticoids (methylprednisolone), myelin basic protein (e.g., 7-capaxone), anti-Fe receptor monoclonal antibodies, hydroorotate dehydrogenase inhibitor, anti-IL2 monoclonal antibodies (e.g., CHI-621 and dacliximab), buspirone, castanospermine, CD-59 (complement factor inhibitor), 5-lipoxygenase inhibitor (e.g., CMI-392), phosphatidic acid synthesis antagonists, ebselen, edelfosine, enlimomab, galaptin, platelet activating factor antagonists, selectin antagonists (e.g., ICAM-4), interleukin-10 agonist, macrocylic lactone, methoxatone, mizoribine, OX-19, peptigen agents, PG-27, protein kinase C inhibitors, phosphodiesterase IV inhibitor, single chain antigen binding proteins, complement factor inhibitor, sialophorin, sirolimus, spirocyclic lactams, 5-hydroxytryptamine antagonist, anti-TCR monoclonal antibodies, CD5 gelonin and TOK-8801, and the like; antibacterial agents (e.g., amikacin sulfate, aztreonam, chloramphenicol, chloramphenicol palmitate, chloramphenicol sodium succinate, ciprofloxacin hydrochloride, clindamycin hydrochloride, clindamycin palmitate, clindamycin phosphate, metronidazole, metronidazole hydrochloride, gentamicin sulfate, lincomycin hydrochloride, tobramycin sulfate, vancomycin hydrochloride, polymyxin B sulfate, colistimethate sodium, colistin sulfate, and the like); antifungal agents (e.g., griseofulvin, keloconazole, and the like); antiviral agents (e.g., interferon gamma, zidovudine, amantadine hydrochloride, ribavirin, acyclovir, and the like); antimicrobials (e.g., cephalosporins (e.g., cefazolin sodium, cephradine, cefaclor, cephapirin sodium, ceftizoxime sodium, cefoperazone sodium, cefotetan disodium, cefutoxime azotil, cefotaxime sodium, cefadroxil monohydrate, ceftazidime, cephalexin, cephalothin sodium, cephalexin hydrochloride monohydrate, cefamandole nafate, cefoxitin sodium, cefonicid sodium, ceforanide, ceftriaxone sodium, ceftazidime, cefadroxil, cephradine, cefuroxime sodium, and the like), penicillins (e.g., ampicillin, amoxicillin, penicillin G benzathine, cyclacillin, ampicillin sodium, penicillin G potassium, penicillin V potassium, piperacillin sodium, oxacillin sodium, bacampicillin hydrochloride, cloxacillin sodium, ticarcillin disodium, azlocillin sodium, carbenicillin indanyl sodium, penicillin G potassium, penicillin G procaine, methicillin sodium, nafcillin sodium, and the like), erythromycins (e.g., erythromycin ethylsuccinate, erythromycin, erythromycin estolate, erythromycin lactobionate, erythromycin siearate, erythromycin ethylsuccinate, and the like), tetracyclines (e.g., tetracycline hydrochloride, doxycycline hyclate, minocycline hydrochloride, and the like), and the like); antioxidants (e.g., N-acetylcsysteine, Vitamin A, Vitamin C, Vitamin E, .beta.-carotene, EUK-8, flavonoids, glutathione, .alpha.lipoic acid, melatonin, retinols, and the like); anti-infectives (e.g., miconazole, vidarabine, inosine, pranobex, vidarabine, inosine prabonex, cefpimizole sodium), fradiomycin, and the like); hormones (e.g., androgens (e.g., danazol, testosterone cypionate, fluoxymesterone, ethyltostosterone, testosterone enanihate, methyltestosterone, fluoxymesterone, testosterone cypionate), estrogens (e.g., estradiol, estropipate, conjugated estrogens), progestins (e.g., methoxyprogesterone acetate, norethindrone acetate), corticosteroids (e.g., triamcinolone, betamethasone, betamethasone sodium phosphate, dexamethasone, dexamethasone sodium phosphate, dexamethasone acetate, prednisone, methylprednisolone acetate suspension, triamcinolone acetonide, methylprednisolone, prednisolone sodium phosphate methylprednisolone sodium succinate, hydrocortisone sodium succinate, methylprednisolone sodium succinate, triamcinolone hexacatonide, hydrocortisone, hydrocortisone cypionate, prednisolone, fluorocortisone acetate, paramethasone acetate, prednisolone tebulate, prednisolone acetate, prednisolone sodium phosphate, hydrocortisone sodium succinate, and the like), thyroid hormones (e.g., levothyroxine sodium) and the like), and the like; psoriasis agents, such as 5-LO inhibitors (e.g., Wy-50295, Wy-49232, Lonapalene, RS-43179, MK-886, L-663536, ETH-615, DUP-654, Zileuton, epocarbazolin-A, and A-64077), 5-LO/CO inhibitors (e.g., BF-397, Tenidap, CP-309, and CP-66248), angiogenesis inhibitors (e.g., platelet factor 4), anticancer antibiotic (e.g., AGM-1470, and TNP-470), anti-inflammatory cytochrome P450 oxidoreductase inhibitors (e.g., DuP-630, and DuP-983), antiproliferative compounds (e.g., Zyn-Linker), arachidonic acid analogues (e.g., CD581, and CD554), arachidonic acid antagonists (e.g., Lonopalene, RS-43179, triamcinolone acetonide with penetration enhancer Azone, betamethasone dipropionate steroid wipe, G-202, Halobetasol propionate, ultravate, Halometasone, C-48401-Ba, and Sicorten), beta-glucan receptor antagonists, betamethasone steroid wipes, calcium metabolic moderators (e.g., Tacalcitol, Bonealfa, TV-02 ointment, Ro-23-6474, KH-1060, Calcipotriol, BMS-181161, BMY-30434, Dovonex, and Divonex), CD4 binding inhibitors (e.g., PIC 060), cell adhesion compounds (e.g., CY-726, VCAM-1, ELAM-1, and ICAM), cell adhesion inhibitors (e.g., selectin inhibitor, GM-1930), cellular aging inhibitors (e.g., Factor X), corticosteroids (e.g., Halobetasol propionate, ultravate, Halometasone, C-48401-Ba, and Sicorten), cyclosporin analogues (e.g., IMM-125), dihydrofolate reductase inhibitors (e.g., G-301, dichlorobenzoprim, methotrexate, and methotrexate in microsponge delivery system), E-selectin inhibitors (e.g., ISIS 4730), endogenous active form of vitamin D3 (e.g., Calcitriol, and Du-026325), fibroblast growth factor antagonists (e.g., Saporin mitotoxin, and Steno-Stat), fumagillin analogues (e.g., AGM-1470, and TNP-470), G-proteins and signal transduction compounds (e.g., CPC-A), gel formulations for acne (e.g., nicotinamide, N-547, and Papulex), growth hormone antagonists (e.g., Octreotide, Sandostatin, Lanreotide, angiopeptin, BIM-23014, and Somatuline), humanized antibodies (e.g., anti-CD4 antibody), hydroorotate dehydrogenase inhibitors (e.g., Brequinar sodium, bipenquinate, and DuP-785), ICAM-1 inhibitors (e.g., ISIS 939), IL-1 and other cytokine inhibitors (e.g., Septanil), IL-1 converting ezyme inhibitors, IL-1 receptor antagonists (e.g., Antril), IL-2 antagonists (e.g., Tacrolimus, Prograf, and FK-506), IL-2 receptor-targeted fusion toxins (DAB389IL-2), IL-8 receptors, immunostimulants (e.g., Thymopentin, and Timunox), immunosuppressants (e.g., XomaZyme-CD5 Plus, cyclosporine, Sandimmune, SR-31747, anti-CD 11, 18 MAb, Tacrolimus, Prograf, FK-506, and FK-507), immunosuppressive agents targeting FK506 (e.g., immunophilins, VX-10367, and VX-10428), immunotoxins MAb directed against CD antigen (e.g., XomaZyme-CD5 Plus), leukotriene antagonists (e.g., Sch-40120, Wy-50295, and Wy49232), leukotriene B4 antagonists (e.g., SC-41930, SC-50605, SC-48928, ONO-4057, LB-457, LY-255283, LY-177455, LY-223982, LY-223980, and LY-255253), leukotriene synthesis inhibitors (MK-886, and L-663536), lipase clearing factor inhibitors (e.g., 1-docosanol, and lidakol), lipid encapsulated reducing agent (e.g., Dithranol), liposomal gel (e.g., Dithranol), LO inhibitors (e.g., CD581, CD554, Masoprocol, and Actinex), lithium succinate ointments (e.g., lithium salts, and Efalith), LO/CO inhibitors (e.g., P-8892, P-8977, CHX-108, and FPL-62064), membrane integrity agonists (e.g., lithium salts, and Efalith), microtubule inhibitors (e.g., Posophyliotoxin-containing compound, and Psorex), octapeptide somatostatin analogues (e.g., Lanreotide, angiopeptin, BIM-23014, and Somatuline), oligonucleotides (e.g., ISIS 4730, ISIS 3801, ISIS 1939, and IL-1 inhibitors), peptide agonists (e.g., octapeptide, and peptide T), PKC inhibitors, phospholipase A2 compounds, pospholipase D compounds, photodynamic anticancer agents (e.g., 5-aminolevulinic acid, and 5-ALA), photodynamic therapies (e.g., benzoporphyrin derivative, synthetic chlorins, synthetic porphyrins, and EF-9), photosensitizer (e.g., Porfirmer sodium), PKC inhibitors (e.g., Safingol, and Kynac), platelet activating factor antagonists (e.g., TCV-309), platelet aggregation inhibitors (e.g., CPC-A), prodrug NSAIDs (e.g., G-201), prostaglandin agonist (e.g., eicosapentaenoic acid +gamma-linolenic acid combination, and Efamol Marine), protein inhibitors (e.g., SPC-103600, and SPC-101210), protein kinase C (PKC) inhibitors (e.g., Ro-31-7549, Ro-31-8161, and Ro-31-8220), protein synthesis antagonists (e.g., Calcitriol, Du-026325, LG-1069, LG-1064, AGN-190168, Namirotene, and CBS-211A), purine nucleoside phosphorylase inhibitors (e.g., BCX-34), radical formation agonists (e.g., benzoporphyrin derivative), recombinant antileukoproteinases (e.g., ALP-242), retinoids (e.g., BMY-30123, LG-1Q69, and LG-1064), retinoid derivatives (e.g., AGN-190168), rapamycin binding proteins (FKBP) (e.g., immunophilins, VX-10367, and VX-10428), second generation monoaromatic retinoids (e.g., Acitretin, and Neotigason), soluble IL-1, IL-4 and IL-7 receptors, somatostatin and somatostatin analogues (e.g., Octreotide, and Sandostatin), steroids, (e.g., AGN-191743), streptomyces anulatus isolates (e.g., epocarbazolin-A), superoxide dismutase (e.g., EC-SOD-B), thymidylate synthase inhibitors (e.g., AG-85, MPI-5002, 5-FU in biodegradable gel-like matrix, 5-FU and epinephrine in biodegradable gel-like matrix, and AccuSite), topical formulations (e.g., P-0751, and P-0802), transglutaminase inhibitors, tyrphostin EGF receptor kinase blockers (e.g., AG-18, and AG-555), VCAM-1 inhibitors (e.g., ISIS 3801), vitamin D analogues (e.g., Ro-23-6474, KH-1060, Calcipotriol, BMS-181161, BMY-30434, Dovonex, and Divonex), vitamin D3 analogues (e.g., Tacalcitol, 20 Bonealfa, TV-02 ointment), and vitamin D3 derivatives (e.g., 1,2-diOH-vitamin D3), and the like; and agents useful for the treatment of carcinomas (e.g., adriamycin, taxol, interleukin-1, interleukin-2 (especially useful for treatment of renal carcinoma), and the like, as well as leuprolide acetate, LHRH analogs (such as nafarelin acetate), and the like, which are especially useful for the treatment of prostatic carcinoma).","The amount of benefit agent to be included may vary depending upon, for example, the ability of the benefit agent to penetrate through the skin, the specific benefit agent chosen, the particular benefit desired, the sensitivity of the user to the benefit agent, the health condition, age, and skin condition of the user, and the like.","In sum, the benefit agent is used in a “safe and effective amount,” which is an amount that is high enough to deliver a desired skin benefit or to modify a certain condition to be treated, but is low enough to avoid serious side effects, at a reasonable risk to benefit ratio within the scope of sound medical judgment.","Formulations The compositions of the present invention can be prepared and administered in a wide variety of topical forms.","For topical formulations of the present invention, dermatologically acceptable carriers can be either solid or liquid.","The compositions of this invention is preferably in the form of topical products that can be applied externally to the skin and can be prepared in accordance with conventional techniques known to those of ordinary skill in the art.","The carrier may take a variety of physical forms such as, for example, creams, dressings, gels, lotions, ointments or liquids.","One could also utilize this in a convenient spray applicator.","Typical carriers include lotions containing water and/or alcohols and emollients such as hydrocarbon oils and waxes, silicone oils, hyaluronic acid, vegetable, animal or marine fats or oils, glyceride derivatives, fatty acids or fatty acid esters or alcohols or alcohol ethers, lanolin and derivatives, polyhydric alcohols or esters, wax esters, sterols, phospholipids and the like, and generally also emulsifiers (nonionic, cationic or anionic), although some of the emollients inherently possess emulsifying properties.","These same general ingredients can be formulated into a cream rather than a lotion, or into gels, or into solid sticks by utilization of different proportions of the ingredients and/or by inclusion of thickening agents such as gums or other forms of hydrophillic colloids.","The compositions according to the invention preferably contain an effective stabilizing amount of an emulsifier.","Any emulsifier that is compatible with the components of the composition can be employed.","Suitable emulsifiers include stearic acid, acetyl alcohol, stearyl alcohol, steareth 2, steareth 20, Acrylates/C10-30 alkyl Acrylate Crosspolymer Particularly preferred is PEMULEN TR-1 (CTFA Designation: Acrylates/10-30 Alkyl Acrylate Crosspolymer).","The composition of the invention may be in the form of an oil-in-water emulsion, a water-in-oil emulsion, or a dispersion.","Liquid form preparations such as lotions or creams include solutions, suspensions, and emulsions, for example, water or DMSO/propylene glycol solutions.","Liquid suspensions suitable for topical use can be made by dispersing the finely divided active component in an appropriate liquid with viscous material, such as natural or synthetic gums, resins, methycellulose, sodium carboxymethylcellulose, and other well-known suspending agents.","Also included are solid form preparations which are intended to be converted, shortly before use, to liquid form preparations for topical administration.","Such liquid forms include solutions, suspensions, and emulsions.","These preparations may contain, addition to the active component, colorants, flavors, fragrances, stabilizers, buffers, artificial and natural sweeteners, dispersants, thickeners, solubilizing agents, and the like.","To prepare dermally applicable formulations it is possible to use the previously mentioned substances and spreadable or liquid hydrocarbons such as Vaseline or paraffin or gels of alkanes and polyethylene, fats and oils of plant or animal origin, which may in part also be hydrated, or synthetic fats such as glycerides of fatty acids C8 -C18, as well as beeswax, cetyl palmitate (e.g., Cutina® CP available from Cognis/BASF), wool wax, wool wax alcohols, fatty alcohols such as cetyl alcohol, stearyl alcohol, polyethylene glycols of molecular weight 200 to 20,000; liquid waxes such as isopropyl myristate, isopropyl stearate, ethyloleate; emulsifiers such as sodium, potassium, ammonium salts of stearic acid or palmitic acid as well as triethalolamine stearate, alkali salts of oleic acid, castor oil acid, salts of sulfurated fatty alcohols such as sodium lauryl sulphate, sodium cetyl sulphate, sodium stearyl sulphate, salts of gallic acid, sterols such as cholesterol, partial fatty acid esters of multivalent alcohols such as ethylene glycol monostearate, glycerol monostearate, pentaerythritol monostearate, partial fatty acid esters of sorbitan, partial fatty acid esters of polyoxyethylene sorbitan, sorbitol ethers of polyoxyethylene, fatty acid esters of polyoxyethylene, fatty alcohol ethers of polyoxyethylene, fatty acid esters of saccharose, fatty acid esters of polyglycerol, lecithin.","Examples of suitable esters nonexclusively include a branched C5 to C22 alkyl alcohol ester of an aromatic acid, a straight-chained or branched C5 to C22 alkyl acid esters of optionally ethyoxylated/propoxylated polyols having from about 3 carbon atoms to about 7 carbon atoms, a branched C5 to C22 alkyl alcohol esters of branched polyacids, a branched or straight-chained Cs to C22 alkyl acid esters of branched and/or unsaturated C5 to C22 alkyl alcohols, a branched or unsaturated C5 to C22 alkyl alcohol esters of an acid selected from the group consisting of adipic acid, succinic acid, maleic acid, sebacic acid, and mixtures thereof, polyether interrupted fatty acid esters, benzoic acid ester of heterogeneous alcohols having from about 8 carbon atoms to about 22 carbon atoms and mixtures thereof with straight-chained or branched C5 to C22 alkyl acid esters of optionally ethyoxylated/propoxylated polyols, benzoic acid esters of heterogeneous alcohols, and mixtures thereof.","Further suitable esters are disclosed in U.S. Pat.","No.","6,762,158, the entire disclosure of which is incorporated herein by reference.","Antioxidants that may for example be used are sodium metabisulphite, ascorbic acid, gallic acid, gallic acid alkyl ester, butylhydroxyanisol, nordihydroguaiacic acid, tocopherols as well as tocopherols .+-.synergitic substances that bind heavy metals through complex formation, for example lecithin, ascorbic acid, phosphoric acid).","Conserving agents that may for example be considered are sorbic acid, p-hydroxybenzoic acid esters (for example lower alkyl esters), benzoic acid, sodium benzoate, trichloroisobutyl alcohol, phenol, cresol, benzethonium chloride and formalin derivatives.","Topical dosage forms include, but are not limited to, sprays, aerosols, creams, lotions, ointments, gels, solutions, emulsions, suspensions, or other forms known to one of skill in the art.","See, e.g., Remington's Pharmaceutical Sciences, 16th and 18th eds., Mack Publishing, Easton Pa. (1980 & 1990); and Introduction to Pharmaceutical Dosage Forms, 4th ed., Lea & Febiger, Philadelphia (1985).","See also Cosmetic Model Formulae—A Compilation of Model Formulae for the Manufacture of Cosmetic Preparations (Henkel KGaA; 1988), the entirety of which is incorporated herein by reference.","Transdermal dosage forms include “reservoir type” or “matrix type” patches, which can be applied to the skin and worn for a specific period of time to permit the penetration of a desired amount of active ingredients.","Suitable excipients (e.g., carriers and diluents) and other materials that can be used to provide transdermal, topical, and mucosal dosage forms are well known to those skilled in the pharmaceutical arts, and depend on the particular tissue to which a given pharmaceutical composition or dosage form will be applied.","The pH of the inventive compositions may also be adjusted to improve delivery of one or more active ingredients.","In another preferred embodiment, the compositions used in the methods of present invention contain a pH-buffering agent.","Preferably, the amount of buffering agent should be that which would result in compositions having a pH ranging from about 4.5 to about 8:5, more preferably from about 5.5 to about 8.5, most preferably from about 6.5 to about 8.0.The buffering agent can be any of the known buffering agents commonly found in topical compositions provided that they are physically and chemically stable with the other ingredients of the composition.","Suitable buffering agents include organic acids such as, but not intended to be restricted to, citric acid, malic acid, and glycolic acid.","Similarly, the polarity of a solvent carrier, its ionic strength, or tonicity can be adjusted to improve delivery.","Compounds such as stearates may also be added to pharmaceutical compositions or dosage forms to advantageously alter the hydrophilicity or lipophilicity of one or more active ingredients so as to improve delivery.","In this regard, stearates can serve as a lipid vehicle for the formulation, as an emulsifying agent or surfactant, and as a delivery-enhancing or penetration-enhancing agent.","Different salts, hydrates or solvates of the active ingredients can be used to further adjust the properties of the resulting composition.","The topical compositions of the present invention may contain a water dispersible component, which is preferably a water soluble solvent.","As used herein, the term “water dispersible component” shall mean a material that produces a uniform, clear or hazy, mixture when combined with at least a weight equivalent of water.","Examples of suitable water dispersible components nonexclusively include polyethylene glycol 400, hexylene glycol, propylene glycol, polypropylene glycol-10 methylglucose ether, ethoxydiglycol, polyethylene glycol-6 caprylic/capric glyceride, ethylene glycol monobutyl ether, polyethylene glycol-8 caprylic/capric glycerides, 3-methoxy-3-methyl-1-butanol, dimethyl isosorbide, and mixtures thereof.","Most preferred water dispersible components include hexylene glycol, dimethyl isosorbide, polyethylene glycol-6 caprylic/capric glyceride, and mixtures thereof.","A further optional component of the compositions of the present invention is a volatile or nonvolatile liquid silicone.","Examples of suitable silicones nonexclusively include the polydimethyl siloxanes and derivatives thereof such as hexamethylsiloxane, dimethicone, dimethiconol, and cyclomethicone, with cyclomethicone being preferred.","Examples of suitable cyclomethicones nonexclusively include cyclotetradimethyl siloxane; cyclopentadimethyl siloxane, cyclohexadimethyl siloxane, cycloheptadimethyl siloxane, and mixtures thereof.","Further optional components of the compositions of the present invention are polymeric emulsifiers and/or thickeners.","Examples of suitable polymeric emulsifiers nonexclusively include polyethylene glycol-30 dipolyhydroxystearate, dimethicone copolyol, substituted acrylates, and mixtures thereof Examples of suitable hydrophilic thickeners nonexclusively include carbomers (e.g., Carbopol® Ultrez polymers available from Lubrizol Corp.; also various carbomer prodcts available from B. F. Goodrich), acrylate copolymers, hydroxyethylcellulose modified with cetyl ether groups, polyvinylmethyl ether/maleic anhydride (PVM/MA) decadiene crosspolymer, and copolymers and mixtures thereof.","Examples of suitable acrylate copolymers nonexclusively include acrylate copolymers available from Rohm & Haas, acrylates/aminoacrylates copolymer, acrylates/steareth-20 itaconate copolymer, acrylates/ceteth-20 itaconate copolymer, acrylates/steareth-20 methacrylate copolymer, and copolymers and mixtures thereof.","The compositions of the present invention may also optionally contain a stability enhancer for the purpose of enhancing the stability of the benefit agent and/or the aesthetics of the composition.","Generally, the stability enhancer may be selected from a nonionic emulsifier, an essentially non-foaming surfactant, or mixtures thereof.","Examples of suitable nonionic emulsifiers include isocetheth-20, oleth-2, mixture of PEG-40 hydrogenated castor oil and trideceth-9, Poloxamer 184, laureth-4, sorbitan trioleate, polyoxyethylene-(2) oleyl ether, sorbitan stearate, cetearyl glucoside, glyceryl oleate, trideceth-9, polyethylene glycol-40 hydrogenated castor oil, and mixtures thereof.","Examples of suitable essentially non-foaming surfactants include non-foaming nonionic surfactants such as sucrose esters, e.g., sucrose cocoate, sucrose stearate and mixtures thereof.","By “essentially non-foaming,” it is meant that the surfactant, when used with the composition of the present invention, has a column height of less than about 20 mm as determined by the Ross-Miles Foam Generation Test.","See 18 (I.)","Oil & Soap 99-102 (1941)(“Ross-Miles Test”), which is incorporated by reference herein.","The composition may either be rinseable with water or may be wiped-off.","Preferably, the essentially non-foaming surfactants are used in embodiments wherein the composition is rinseable with water.","The composition may also optionally contain a foaming surfactant.","The foaming surfactant may be non-ionic, cationic, amphoteric, or anionic.","By “foaming,” it is meant that the surfactant, when used with the composition of the present invention, has a column height of foam greater than about 20 mm as determined by the Ross-Miles Test.","Preservatives for the formulations herein are benzoic acid and derivatives thereof, namely, butylparaben, ethylparaben, methylparaben, propylparaben, sodium benzoate, and mixtures thereof.","Typical use of benzoic-acid-derived preservative is a mixture of methylparaben comprising up to 0.3 percent by weight of the treating composition and propylparaben comprising up to 0.1 percent by weight of the treating composition.","Other useful preservatives include alcohol, benzalkonium chloride, benzethonium chloride, benzyl alcohol, bronopol, cetrimide, chlorhexidine, chlorobutanol, chlorocresol, cresol, glycerin, imidurea, phenol, phenoxyethanol, phenylethyl alcohol, phenylmercuric acetate, phenylmercuric borate, phenylmercuric nitrate, potassium sorbate, propylene glycol, sodium propionate, sorbic acid and thimerosal.","Among the inactive ingredients are surfactants and emulsifying agents.","These ingredients take on importance as the use thereof improves absorption, coverage, appearance, and feel of the product.","Some suitable emulsifying agents are acacia, anionic emulsifying wax, carbomer, carboxymethyl cellulose, cetostearyl alcohol, cetyl alcohol, cholesterol, diethanolamine, glyceryl monostearate, hydrous lanolin, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, lanolin, lanolin alcohols, lecithin, methylcellulose, mineral oil and lanolin alcohols, monobasic sodium phosphate, monoethanolamine, nonionic emulsifying wax, oleic acid, poloxamer, polyoxyethylene alkyl ethers, polyoxyethylene castor oil derivatives, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates, propylene glycol alginate, sodium lauryl sulfate, sorbitan esters, stearic acid, triethanolamine, and xanthan gum.","Frequently mixtures of complimentary surfactants are used in a given formulation.","Suitable anionic surfactants are lauryl sulfates, including sodium lauryl sulfate, triethanolamine lauryl sulfate, and ammonium lauryl sulfate; laureth sulfates,including sodium laureth sulfate, triethanolamine laureth sulfate, and ammonium laureth sulfate; sarcosines, including lauryl sarcosine, and sodium lauryl sarcosinate; sulfosuccinates, including disodium oleamine sulfosuccinate, and sodium dioctyl sulfosuccinate; and docusate sodium.","The cationic surfactants are benzalkonium chloride, benzethonium chloride, and cetrimide.","The nonionic surfactants are glyceryl monooleate, polyvinyl alcohol, sorbitan esters, povidone, crospovidone, polyoxyethylene fatty alcohols, polyoxyethylene sorbitol esters, and alkanolamides.","Additionally, amphoteric detergents such as betaines, sultaines, and imidazolinium derivatives are used, and particularly ingredients such as cocamidopropyl betaine and sodium lauraminopropionate.","In ointment and cream preparations, emollients form a vehicle to carry the active ingredients to the site of the immune response and the associated dermatitis.","The emollient group from which these carriers are selected include allantoin, cetostearyl alcohol, cetyl esters wax, cocoa butter, cholesterol, dimethicone, glycerin, glyceryl monostearate, isopropyl myristate, isopropyl palmitate, kaolin, lecithin, light mineral oil, mineral oil, mineral oil and lanolin alcohols, petrolatum, and petrolatum and lanolin alcohols.","The carrier can be any suitable aqueous dispersion material, cream, lotion, or ointment, which may include, for example hydrocolloids, plasdone, methyl cellulose, hydroxypropyl cellulose, lanolin, mineral oil, petroleum jelly, polyalkylene glycols such as polyethylene glycols, or mixtures thereof.","The formulations may contain surfactants, antioxidants, and stabilizers such as benzoic acid, sorbic acid, parabens, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), vitamin E, sarcosonates, and the like.","The benefit agents can also be combined with astringents such as witch hazel, aluminum acetate, aluminum sulfate, zinc oxide, zinc acetate, sodium bicarbonate, and calamine.","One of the functions of the formulations when applied to contact dermatitis is to remove the irritant material from the skin.","This requires astringent activity, and the addition of aluminum acetate, zinc oxide, zinc acetate, sodium bicarbonate, calamine, witch hazel, zinc carbonate, and aluminum hydroxide may be employed to enhance this physical property.","A preferred carrier material includes water, glycerin, cetyl palmitate, mineral oil, caprylic/capric triglyceride, octyldodecanol, cetyl alcohol, glyceryl stearate, colloidal oat flour, dimethicone, PEG-40 stearate, carbomer, sodium hydroxide, phenoxy ethanol, caramel III coloring, DMDM hydantoin, and iodopropynyl butylcarbamate.","Glycerin, also called glycerol, acts as a humectant, skin protectant, and solvent present in all natural lipids (fats), whether animal or vegetable.","Whether natural or synthetic, glycerin is a humectant and extremely hygroscopic, meaning it readily absorbs water from other sources, attracting water from the environment and from the lower layers of skin (dermis) and increasing the amount of water in the surface layers of skin.","Another aspect of glycerin's benefit is that it is a skin-identical ingredient, meaning it is a substance found naturally in skin.","In that respect it is one of the many substances in skin that help maintain the outer barrier and prevent dryness or scaling.","The Food and Drug Administration (FDA) includes glycerin on its list of direct food additives considered Generally Recognized As Safe (GRAS), and on its list of approved indirect food additives.","Glycerin is also an FDA-approved active ingredient in Over-the-Counter (OTC) skin protectant drug products and ear drying products, and it is an approved demulcent for the eyes.","Cetyl palmitate acts as an emollient, acting as a lubricant on the skin's surface, which gives the skin a soft and smooth appearance.","The palmitates generally are esters of palmitic acid and ethylhexyl, cetyl, or isopropyl alcohol.","In cosmetics and personal care products, they all function as skin conditioning agents and emollients.","The palmitates are efficient opacifiers in cream and lotion shampoos.","Isopropyl Palmitate also functions as a binder.","The safety of the palmitates has been assessed by the Cosmetic Ingredient Review (CIR) Expert Panel.","The CIR Expert Panel evaluated the scientific data and concluded that Ethylhexyl Palmitate, Cetyl Palmitate and Isopropyl Palmitate were safe as cosmetic ingredients.","In 2001, the CIR Expert Panel considered available new data on Ethylhexyl, Cetyl and Isopropyl Palmitate and reaffirmed the above conclusion.","Light mineral oil acts as an emollient, skin protectant, and solvent.","Mineral oil functions as an emollient skin conditioning agent , an occlusive skin protectant, and as a solvent.","The FDA permits the use of mineral oil as an active ingredient in the following OTC drug product categories: anorectal drugs, skin protectants, and ophthalmic emollients.","Caprylic/capric triglyceride (CAS No.","124-07-2) acts as a moisturizer, viscosity modulator, inactive carrier, and stabilizer.","Caprylic/capric triglyceride is an oily liquid made from coconut oil.","It is used in cosmetics and other personal care products, such as face creams, lipstick, eye makeup and foundations.","It can also be used in perfumes, moisturizers and sunscreens.","It is found naturally in foods but can also be made by industrial processes.","Caprylic/capric triglyceride has a number of useful properties in the formulation of cosmetics and, in particular, face creams.","Caprylic/capric triglyceride creates a barrier on the skin's surface, decreasing the amount of moisture lost through the skin, functioning not only to prevent dryness in skin, but also as a skin conditioning agent.","It provides a slippery feeling and promotes dispersion of pigments in various colored cosmetics.","Caprylic/capric triglycerides have a low viscosity.","This property allows it to alter the thickness of a particular cosmetic product.","Adding caprylic/capric triglycerides to thick face creams helps thin them out to the desired thickness.","Caprylic/capric trigylceride does not readily oxidize.","It is particularly useful as a stabilizer of emulsions.","This property is particularly useful in facial creams and other cosmetic products, helping to give them a longer shelf life.","The Food and Drug Administration lists caprylic/capric triglyceride as Generally Recognized As Safe, or GRAS, for use as a direct food additive.","In addition, caprylic/capric triglyceride has been assessed by the Cosmetic Ingredient Review Expert Panel, which evaluated the scientific data and concluded, and reaffirmed in 2001, that it was safe as it was being used at that time.","Similarly suitable triglyceride materials include medium-chain triglyceride oil (CAS 65381-09-1) available as MCT oil from Acme-Hardesty Oleochemicals.","Octyldodecanol (CAS No.","5333-42-6; Tegosoft® G20 available from Evonik) acts as a stabilizer, emulsifier, lubricant, and solvent.","Octyldodecanol helps to form emulsions and prevent an emulsion from separating into its oil and liquid components.","These ingredients also reduce the tendency of finished products to generate foam when shaken.","When used in the formulation of skin care products, octyldodecanol acts as a lubricant on the skin surface, which gives the skin a soft, smooth appearance.","The safety of Octyldodecanol and related ingredients has been assessed by the Cosmetic Ingredient Review (CIR) Expert Panel.","The CIR Expert Panel evaluated the scientific data and concluded that octyldodecanol was safe for use in cosmetics and personal care products.","In 2004, the CIR Expert Panel considered available new data on octyldodecanol and reaffirmed the above conclusion.","Octyldodecanol may be used in cosmetics and personal care products marketed in Europe according to the general provisions of the Cosmetics Directive of the European Union.","Cetyl alcohol (CAS No.","36653-82-4) acts as an emollients, thickeners, and emulsifier.","Cetyl alcohol and the other fatty alcohols keep an emulsion from separating into its oil and liquid components.","These ingredients are also used to alter the thickness of liquid products and to increase foaming capacity or to stabilize foams.","The safety of cetyl alcohol has been assessed by the Cosmetic Ingredient Review (CIR) Expert Panel.","The CIR Expert Panel evaluated the scientific data and concluded that this fatty alcohol was safe for use as a cosmetic ingredient.","In 2005, the CIR Expert Panel considered available new data on cetearyl alcohol and the other fatty alcohols and reaffirmed the above conclusion.","If they are derived from plants, cetearyl, cetyl, isostearyl, myristyl and behenyl alcohols may be used in cosmetics and personal care products marketed in Europe according to the general provisions of the Cosmetics Directive of the European Union.","Ingredients of animal origin must comply with European Union animal by-products regulations.","Glyceryl stearate (CAS Nos.","11099-07-3, 31566-31-1) may act as an emulsifier, humectant, lubricant, or solvent.","As an emulsifier it assists in forming neutral, stable emulsions; it is also a solvent, humectant, and consistency regulator in water-in-oil and oil-in-water formulations.","It is typically derived from palm kernel or soy oil for cosmetic use.","Glyceryl stearate helps to form emulsions by reducing the surface tension of the substances to be emulsified.","The safety of Glyceryl Stearate has been assessed by the Cosmetic Ingredient Review (CIR) Expert Panel.","The CIR Expert Panel evaluated the scientific data and concluded that Glyceryl Stearate was safe form use in cosmetics and personal care products.","The CIR Expert Panel reviewed chronic studies of glyceryl stearate that showed no adverse effects on reproduction, and no carcinogenic effects.","Human exposure studies of products containing glyceryl stearate and glyceryl stearate SE, as well as clinical experience, have shown these compounds to be non-sensitizing, non-phototoxic and non-photosensitizing.","If they are made from plants, glyceryl stearate and glyceryl stearate SE may be used in cosmetics and personal care products marketed in Europe according to the general provisions of the Cosmetics Directive of the European Union.","Ingredients made from animal sources must comply with the European Union animal by-products regulations.","A suitable material is available from Protameen Chemicals Inc. under the trade name “Protachem GMS-450.” Colloidal oat flour (CAS No.","281-672-4) may act as a moisturizer, skin protectant, pH buffer, and anti-inflammatory agent, and may have anti-irritant and anti-inflammatory properties.","As a skin protectant, colloidal oatmeal temporarily protects injured or exposed skin from harmful or annoying stimuli, and may therefore provide relief to the skin.","Oatmeal has been used for centuries as a soothing agent to relieve itch and irritation associated with various xerotic dermatoses.","In 1945, a ready to use colloidal oatmeal, produced by finely grinding the oat and boiling it to extract the colloidal material, became available.","Today, colloidal oatmeal is available in various dosage forms from powders for the bath to shampoos, shaving gels, and moisturizing creams.","Currently, the use of colloidal oatmeal as a skin protectant is regulated by the U.S. Food and Drug Administration (FDA) according to the Over-The-Counter Final Monograph for Skin Protectant Drug Products issued in June 2003.Its preparation is also standardized by the United States Pharmacopeia.","The many clinical properties of colloidal oatmeal derive from its chemical polymorphism.","The high concentration in starches and beta-glucan is responsible for the protective and water-holding functions of oat.","The presence of different types of phenols confers antioxidant and anti-inflammatory activity.","Some of the oat phenols are also strong ultraviolet absorbers.","The cleansing activity of oat is mostly due to saponins.","Its many functional properties make colloidal oatmeal a cleanser, moisturizer, buffer, as well as a soothing and protective anti-inflammatory agent.","The Food and Drug Administration (FDA) reviewed the safety and efficacy of colloidal oatmeal and approved its use as an active ingredient in Over-the-Counter (OTC) skin protectant drug products at a minimum concentration of 0.007%, or 0.003% when used in combination with mineral oil.","When used as a skin protectant in an OTC skin protectant drug product, this ingredient must be called colloidal oatmeal.","The Cosmetic Ingredient Review (CIR) has deferred evaluation of this ingredient because the safety has been assessed by FDA.","This deferral of review is according to the provisions of the CIR Procedures.","Avena Sativa (Oat) Kernel Meal and colloidal oatmeal may be used in cosmetics and personal care products marketed in Europe according to the general provisions of the Cosmetics Directive of the European Union.","Dimethicone (CAS No.","9006-65-9) may act as a moisturizer and emollient.","Dimethicone is a silicone based polymer that forms a protective barrier on the skin to help retain moisture.","Dimethicone's oil-like consistency also gives it emollient properties.","The Food and Drug Administration (FDA) reviewed the safety of dimethicone and approved its use as a skin protectant active ingredient in over-the-counter (OTC) drug products.","The safety of Dimethicone has been assessed by the Cosmetic Ingredient Review (CIR) Expert Panel.","The CIR Expert Panel evaluated the scientific data and concluded that these ingredients were safe for use in cosmetics.","Dimethicone, methicone, and the related polymers may be used in cosmetics and personal care products marketed in Europe according to the general provisions of the Cosmetics Directive of the European Union.","The World Health Organization Joint FAO/WHO Expert Committee on Food Additives has established an acceptable daily intake level for Dimethylpolysiloxane (Dimethicone) of 0 to 1.5 mg/kg body weight.","PEG-40 stearate (CAS No.","9004-99-3) may act as an emulsifier.","PEG-40 stearate typically functions as a cleansing agent, but also helps keep ingredients solubilized.","Suitable materials include a PEG-40 stearate available from Lipo Chemicals Inc. under the trade name “Lipopeg® 39S.”The safety of the PEG stearates has been assessed by the Cosmetic Ingredient Review (CIR) Expert Panel.","The CIR Expert Panel evaluated the scientific data and concluded that PEG-2, -6, -8, -12, -20, -32, -40, -50, -100 and -150 stearates are safe for use in cosmetics and personal care products.","In 2002, as part of the scheduled re-evaluation of ingredients, the CIR Expert Panel considered available new data on the PEG Stearates and reaffirmed the above conclusion.","In the CIR Safety Review, the PEG stearates, whose average number of ethylene oxide monomers range from 2 to 150, were nonlethal at levels up to 10 g/kg.","They gave evidence of only minimal skin irritation and minimal eye irritation when tested at 100%.","PEG-8, -40 and -100 stearates produced no significant changes in growth, histopathologic observations or hematologic values in long-term feeding studies.","Multiple generation studies of PEG-8 and -40 stearates were negative for effects on reproduction.","Clinical studies on the PEG stearates indicated that these ingredients were neither irritants nor sensitizers at concentrations of 25% or greater.","There was no evidence of phototoxicity or photosensitization of PEG-2 or -8 stearates.","Because the smaller PEG stearates were not photosensitizing the CIR Expert Panel did not expect the larger ingredients to be photosensitizing.","The CIR Expert Panel concluded that safety data on individual PEG stearates were sufficient for a decision regarding the safety of the entire group.","Carbomer polymers may act a thickeners and formulation stabilizers.","Carbomers are synthetic polymers of varying molecular weights that can be used to thicken suspend and stabilize cosmetic formulations.","Requiring very low concentrations, carbomers are often used to adjust the viscosity of cosmetic preparations.","They dry quickly and are not film forming.","Carbomers as an ingredient family resist bacterial attack and do not readily support mold growth.","Under normal conditions, gels prepared with sodium carbomer neither prevent nor promote the growth of microorganisms; therefore the addition of a suitable preservative system is advisable.","The safety of the Carbomer has been assessed by the Cosmetic Ingredient Review (CIR) Expert Panel.","The CIR Expert Panel evaluated the scientific data and concluded that carbomer polymers were safe as ingredients in cosmetics and personal care products.","In 2001, as part of the scheduled re-evaluation of ingredients, the CIR Expert Panel considered available new data on carbomer polymers and reaffirmed the above conclusion.","The CIR Expert Panel reviewed acute oral studies showing that carbomer polymers have low toxicities when ingested.","Minimal skin irritation and no to moderate eye irritation were observed.","Subchronic feeding studies with a carbomer polymer resulted in lower than normal body weights, but no abnormal changes were observed in the organs.","Some gastrointestinal irritation and marked pigment deposition within specific cells in the liver, called Kupffer cells, were seen in studies with carbomer.","Clinical studies with carbomers showed that these polymers have low potential for skin irritation and sensitization at concentrations up to 100%.","A carbomer polymer demonstrated low potential for phototoxicity and photo-contact allergenicity.","The Carbomers may be used in cosmetics and personal care products marketed in Europe according to the general provisions of the Cosmetics Directive of the European Union.","Sodium Hydroxide (CAS No.","1310-73-2) may function as a pH modulator, an alkali used to neutralize acids in maintenance of pH of the cream.","The Food and Drug Administration (FDA) includes sodium hydroxide on its list of substances affirmed as Generally Recognized as Safe (GRAS) for direct addition to food.","Sodium hydroxide, as well as calcium hydroxide, is also approved as an indirect food additive for use as a defoaming agent in the manufacture of paper and paperboard used as food packaging.","Sodium hydroxide is listed in the Cosmetics Directive of the European Union (see Annex III) and may be used at the following concentrations and pH values: 5% by weight in nail cuticle solvents, 2% by weight in hair straighteners for general use, 4.5% by weight in hair straighteners for professional use, up to a pH 12.7 in depilatories, and up to pH 11 in other uses as a pH adjuster.","The nail cuticle solvents and the general use hair straighteners containing these ingredients must be labeled “contains alkali, avoid contact with eyes, can cause blindness, keep out of reach of children.” The professional hair straighteners must be labeled “for professional use only, avoid contact with eyes, can cause blindness.” Depilatories containing these ingredients must include the following on the label: “Keep out of reach of children, avoid contact with eyes.” Phenoxy ethanol (CAS No.","9004-78-8) may act as a preservative, anti-oxidant, or anti-microbial.","Phenoxyethanol is used as a preservative in cosmetics.","Phenoxyethanol prevents or retards microbial growth, and thus protects cosmetics and personal care products from spoilage.","It may also be used in fragrances.","Phenoxyethanol is usually synthesized for commercial use but it can also be found naturally in products such as green tea.","The CIR Expert Panel reviewed safety data on phenoxyethanol and noted that it was practically nontoxic via oral and dermal administration.","In a subchronic oral study, increased weights of some organs were noted when high doses of phenoxyethanol were administered.","The doses in this study were considered to be much higher than those resulting from use of cosmetics and personal care products containing phenoxyethanol.","In dermal laboratory studies, phenoxyethanol did not cause any birth defects.","Phenoxyethanol was not mutagenic.","In clinical studies, phenoxyethanol was neither a primary nor a cumulative irritant, it did not cause delayed hypersensitivity, and was it nonphototoxic.","Phenoxyethanol is listed as 2-Phenoxyethanol in Annex VI, Part 1 (preservative which cosmetic products may contain) of the Cosmetics Directive of the European Union and may be used in concentrations up to 1%.","Caramel Coloring III (CAS No.","8028-89-5) is a coloring agent derived from heating edible sugar.","In cosmetics and personal care products, caramel is used in the formulation of a wide variety of product types as a coloring agent.","The Food and Drug Administration (FDA) includes caramel on its list of substances considered Generally Recognized As Safe (GRAS) as a multipurpose food substance.","FDA also lists caramel as a color additive exempt from certification.","Caramel is determined to be safe for use in coloring cosmetics and personal care products, including products applied to the lips and area of the eye.","The Cosmetic Ingredient Review (CIR) has deferred evaluation of this ingredient because the safety has been assessed by FDA.","This deferral of review is according to the provisions of the CIR Procedures.","Caramel functions as a colorant in cosmetics and personal care products.","To be used as a colorant in the United States, caramel must comply with FDA manufacturing requirements.","For example, only certain food-grade acids, alkalis, and salts may be used to assist carmelization, in amounts consistent with good manufacturing practice.","Caramel is listed in Annex IV, Part I (coloring agent allowed for use in cosmetic products) of the Cosmetics Directive of the European Union and may be used without restriction when purity requirements included in food regulations are fulfilled.","DMDM Hydantoin (e.g., Glydant® Plus available from Lonza) may function as a preservative and anti-microbial.","It is used as an antimicrobial formaldehyde releaser preservative with the trade name Glydant.","DMDM hydantoin is an organic compound belonging to a class of compounds known as hydantoins.","It is used in the cosmetics industry and found in products like shampoos, hair conditioners, hair gels and skin care products.","DMDM hydantoin works as a preservative because the released formaldehyde makes the environment less favorable to the microorganisms.","The Cosmetic Ingredient Review (CIR) Expert Panel has evaluated DMDM hydantoin and concluded that it was safe to a great majority of consumers but has limited the concentration to 0.2% free formaldehyde due to the skin sensitivity of some individuals to this agent.","A study found “[a]n increase in the use of DMDM hydantoin in cosmetic products will also inevitably increase the risk of cosmetic dermatitis in consumers allergic to formaldehyde.","The CIR Safety Review determined DMDM hydantoin is poorly absorbed from the skin.","In a laboratory study, oral exposure to DMDM hydantoin did not result in any adverse effects.","The CIR Expert Panel noted that DMDM hydantoin is a formaldehyde donor in aqueous media.","They attributed positive results in some in vitro mutagenicity studies to formaldehyde release.","In these studies, the concentrations of DMDM hydantoin tested were higher than those used in cosmetic and personal care products, likely resulting in much higher concentrations of formaldehyde than found in products.","Clinical studies revealed some observations of skin irritation which could also be related to the release of formaldehyde from DMDM hydantoin.","The CIR Expert Panel has reviewed the safety of formaldehyde in cosmetics and personal care products and concluded that it was safe to a great majority of consumers but has limited the concentration to 0.2% free formaldehyde due to the skin sensitivity of some individuals to this agent.","The amount of DMDM hydantoin required to preserve a product (less than 1%) does not expose the consumer to concentrations of formaldehyde above the 0.2% limit for formaldehyde recommended by the CIR Expert Panel.","DMDM hydantoin, called dimethylol, dimethylhydantoin [1,3-Bis(hydroxymethyl)-5,5-dimethylimidazolidine-2,4-dione], is listed in Annex VI, Part I (preservatives which cosmetics products may contain) of the Cosmetics Directive of the European Union and may be used in cosmetics and personal care products at a maximum concentration of 0.6%.","If the concentration of released formaldehyde exceeds 0.05% in the finished product it must be labeled “contains formaldehyde.” Iodopropynyl Butylcarbamate (CAS No.","55406-53-6) may function as a preservative, anti-microbial, and anti-fungal.","The active ingredient of this product, IPBC, is recognized by the CTFA in the USA for use in cosmetic and personal care products and listed by the EU as an approved cosmetic preservative.","IPBC-II is a colorless to light yellow, clear viscous liquid at room temperature.","It is a unique and cost effective preservative that provides a high level of antimicrobial activity.","It is remarkably proficient in inhibiting the growth of yeasts and molds.","IPBC is compatible with essentially all cosmetic ingredients, such as surfactants, emulsifiers, proteins and herbal extracts.","Methods of Preparation The compositions in general are prepared from the imidazole compound and colloidal oatmeal, as well as any other desired benefit agents.","If desired additional ingredients such as surfactants and emulsifying agents, antihistamines, topical anesthetics, topical antipruritics, astringents, and emollients may be added.","The ingredients may be added in such steps and amounts and processing varied as to create a spray, cream, gel, ointment, or lotion.","The advantages of the invention and specific embodiments of the skin care compositions prepared in accordance with the present invention are illustrated by the following examples.","It will be understood, however, that the invention is not confined to the specific limitations set forth in the individual examples, but rather defined within the scope of the appended claims.","EXAMPLES Example 1 A topical formulation containing 100 mg of THI in 10 g of base cream was prepared as follows.","To 1.0 g of base cream (water, glycerin, mineral oil, cetyl palmitate, caprylic/capric triglyceride, octyldodecanol, cetyl alcohol, glyceryl stearate, colloidal oat flour, dimethicone, PEG-40 stearate, carbomer, sodium hydroxide, phenoxy ethanol, caramel III coloring, DMDM hydantoin, iodopropynyl butylcarbamate) was added 100 mg of THI (CAS No.","94944-70-4) portionwise with levigation of the powder between additions.","A smooth cream was obtained by levigation in a marble mortar and pestle.","A dime-sized portion of the levigated material was then incorporate geometrically with similar-sized portions of base and mixed thoroughly.","Geometric mixing with additional cream base was repeated until 9.9 g of base was incorporated, yielding a 1.0% THI cream.","Examination of the cream on a mixing plate suggested the THI was at least partially dissolving in the cream base.","Application of the finished cream to the skin left no residue.","Example 2 Eczema/Psoriasis Lotion Treatment The treatment test regime consists of three concentrations ranging from 0.5% to 2% of the active ingredient THI.","Affected areas are documented with before and after photos and notes of observations from each step in the treatment regime are recorded.","Three lotions respectively containing 0.5% (Disc “A”), 1.0% (Disc “B”), and 2% (Disc “C”) by weight of THI are used in the treatment test.","Standard Application Protocol The area to which the lotion is to be applied to is cleaned before starting treatment.","The lotion from Disc “A” is applied to just cover the affected area twice a day, once in morning and once again in evening.","Any physical changes observed are noted; the treatment is discontinued if redness occurs.","This regime is continued for one week.","If the desired effect is realized at this concentration, applications at 0.5% concentration are continued without moving on to the next higher concentration.","The treatment is discontinued if redness occurs.","At the start of week two if no observed relief is noticed with 0.5% lotion from Disc “A”, treatment is begun with 1.0% lotion from Disc “B”.","The application regime just described is repeated substituting the 1.0% lotion from disc “B” for one week.","If the desired effect is realized at 1.0% concentration, the applications are continued at this concentration without moving on to the next higher concentration, Any physical changes observed are noted; the treatment is discontinued if redness occurs.","At the start of week three if no observed relief is noticed with 1.0% lotion from Disc “B”, treatment is begun with 2.0% lotion from Disc “C”.","The application regime just described is repeated substituting the 2.0% lotion from disc “C” for one week.","If the desired effect is realized at 2.0% concentration, the applications are continued at this concentration.","Any physical changes observed are noted; the treatment is discontinued if redness occurs.","Example 3 Test Case for Excema The subject is a 10-year-old Caucasian male, in otherwise excellent health, suffering from excema over a portion of the subject's thighs.","The subject rated the severity of the excema before treatment according to the protocol of Example 2 as 9 on a scale of 0 to 10, where 0 represents no psoriasis or excema, and 10 represents extremely bad psoriasis or excema.","The subject had been previously treated with locoid lipid oil and hyderm topical hydrocortisone treatments with little to moderate success.","The subject rated the effectiveness of the locoid lipid oil as 2 and of the hyderm cream as 4 on a scale of 1 to 5, where 1 represents an extremely useful treatment, and 5 represents no change in symptoms.","After following the treatment protocol of Example 2 using only the 0.5% concentration lotion, the subject rated the severity of excema after treatment as 0.Example 4 Test Case for Psoriasis The subject is a 63-year-old Caucasian male, apparently in otherwise good health, suffering from psoriasis over a portion of the subject's chest and lower back.","The subject had been suffering from moderate to severe psoriasis in these areas for more than 40 years and was able to obtain only moderate relief during that time from a variety of treatments including UV radiation, and at the time immediately prior to the treatment according to the protocol of Example 2 had been taking methotrexate orally and applying Daivonet or Daivonex ointments topically.","Following the treatment protocol of Example 2 for two weeks and three weeks concluding with the 2.0% concentration lotion substantially relieved the subject's psoriatic symptoms."]],"string":"[\n [\n \"COMPOSITION AND METHOD FOR TREATMENT OF SYMPTOMS ASSOCIATED WITH VARIOUS SKIN CONDITIONS\",\n \"Compositions containing imidazole-based compounds, and optionally, colloidal oatmeal, for the treatment, prevention, and management of symptoms, conditions, diseases, and disorders of the skin.\",\n \"Also, methods for the treatment, prevention, and management of symptoms, conditions, diseases, and disorders of the skin using compositions containing imidazole-based compounds, and optionally, colloidal oatmeal.\"\n ],\n [\n \"1.A composition comprising colloidal oatmeal and an imidazole compound of the formula wherein: R1 is hydrogen, alkyl or aryl; R6 is OR10 or OC(O)R10; R7 is OR11 or OC(O)R11; R8 is OR12 or OC(O)R12; and R9 is hydrogen, CH2OR13 or CH2OC(O)R13; and each of R10, R11, R12 and R13 is independently hydrogen or lower alkyl, and pharmaceutically, dermatologically, or cosmetically acceptable salts thereof, contained in a dermatologically acceptable carrier.\",\n \"2.The composition of claim 1, in the form of a spray, cream, gel, lotion, or ointment.\",\n \"3.The composition of claim 1, wherein the carrier comprises one or more excipients selected from the group consisting of surfactants, solvents, tonicity modifiers, thickeners, emulsifiers, preservatives, dispersants, buffers, stabilizers, fragrances, colorants, and flavorings.\",\n \"4.The composition of claim 1, further comprising one or more compounds or compositions selected from the group consisting of antipruritics, emollients, antiseptics, antifungals, antiinflammatories, immunosuppressants, psoriasis agents, anti-cancer agents, antibiotics, antiparasitics, antioxidants, antibacterials, antimicrobials, antiretrovirals, moisturizers, sunscreens, NSAIDs, hormones, steroids, analgesics, antihistamines, and antipyretics.\",\n \"5.The composition of claim 1, comprising 0.01% to 10% by weight of 2-acetyl-4-tetrahydroxybutylimidazole or a pharmaceutically, dermatologically, or cosmetically acceptable salt thereof and 0.01% to 25% by weight of the colloidal oatmeal.\",\n \"6.The composition of claim 5, comprising 0.1% to 5% by weight of 2-acetyl-4-tetrahydroxybutylimidazole or a pharmaceutically, dermatologically, or cosmetically acceptable salt thereof and 0.1% to 10% by weight of the colloidal oatmeal.\",\n \"7.The composition of claim 6, comprising 0.5% to 2% by weight of 2-acetyl-4-tetrahydroxybutylimidazole or a pharmaceutically, dermatologically, or cosmetically acceptable salt thereof and 0.5% to 2% by weight of the colloidal oatmeal.\"\n ],\n [\n \" FIELD OF THE INVENTION This invention relates to compositions containing imidazole-based compounds, and optionally, colloidal oatmeal, and to methods of their use for the treatment, prevention, and management of symptoms, conditions, diseases, and disorders of the skin.\"\n ],\n [\n \" SUMMARY OF THE INVENTION One aspect of the invention relates to a method of treating, managing, or preventing a dermatological or skin condition, which comprises topically administering to a subject in need thereof a therapeutically or prophylactically effective composition comprising an imidazole compound of the formula: wherein: R 1 is hydrogen, alkyl or aryl; R 6 is OR 10 or OC(O)R 10 ; R 7 is OR 11 or OC(O)R 11 ; R 8 is OR 12 or OC(O)R 12 ; and R 9 is hydrogen, CH 2 OR 13 or CH 2 OC(O)R 13 ; and each of R 10 , R 11 , R 12 and R 13 is independently hydrogen or lower alkyl, and pharmaceutically, dermatologically, or cosmetically acceptable salts thereof.\",\n \"Another aspect of the invention relates to a method of caring for skin, which comprises topically administering to the skin of a subject in need thereof a composition comprising the imidazole compound in an amount and for a time sufficient to effect a change in the skin.\",\n \"Another aspect of the invention relates to a method of delivering or depositing a benefit agent onto skin, which comprises topically administering to the skin of a subject a composition comprising the imidazole compound contained in a dermatologically acceptable carrier.\",\n \"Another aspect of the invention relates to a method of suppressing a dermatologic immune response in a patient in need thereof, comprising topically administering an effective composition comprising the imidazole compound contained in a dermatologically acceptable carrier.\",\n \"Another aspect of the invention relates to a composition comprising an imidazole compound of the formula: wherein: R 1 is hydrogen, alkyl or aryl; R 6 is OR 10 or OC(O)R 10 ; R 7 is OR 11 or OC(O)R 11 ; R 8 is OR 12 or OC(O)R 12 ; and R 9 is hydrogen, CH 2 OR 13 or CH 2 OC(O)R 13 ; and each of R 10 , R 11 , R 12 and R 13 is independently hydrogen or lower alkyl, and pharmaceutically, dermatologically, or cosmetically acceptable salts thereof.\",\n \"Another aspect of the invention relates to compositions containing combinations of imidazole-based compounds and, optionally, colloidal oatmeal, and to methods of their use for the treatment, prevention, and management of inflammatory or immune-mediated symptoms, conditions, diseases, and disorders of the skin.\",\n \"Another aspect of the invention relates to combinations of imidazole-based compounds and, optionally, colloidal oatmeal, and to methods of their use for the treatment, prevention, and management of various skin symptoms, conditions, diseases, and disorders.\",\n \"Another aspect of the invention relates to combinations of imidazole-based compounds and colloidal oatmeal and to methods of their use for the treatment, prevention, and management of atopic dermatitis, seborrheic dermatitis, contact dermatitis, cutaneous sarcoidosis, drug induced photosensitivity, fixed drug eruptions, id reactions, bullous skin diseases, discoid lupus erythematosus, subacute cutaneous lupus, alopecia areata, sea bathers eruptions, psoriasis, dyshidrotic eczema, and pompholyx.\",\n \"Another aspect of the invention relates to compositions and methods for treating inflammatory and/or immune-mediated dermatoses with imidazole-based compounds and combinations of imidazole-based compounds and colloidal oatmeal.\",\n \"Another aspect of the invention relates to care, supplement, and pharmaceutical compositions containing imidazole-based compounds, colloidal oatmeal, and other ingredients used to treat disorders of the skin, as well as to compositions suitable for use in personal care applications, and in particular skin care compositions, which effectively deliver and/or deposit various benefit agents into and onto the skin.\",\n \"Another aspect of the invention relates to compositions and methods for treating contact dermatitis.\",\n \"These and further aspects of the claimed invention will now be explained in more detail.\",\n \"detailed-description description=\\\"Detailed Description\\\" end=\\\"lead\\\"?\"\n ],\n [\n \"CROSS-REFERENCE TO RELATED APPLICATIONS This application is a divisional application, claiming benefit 35 U.S.C.\",\n \"§ 120 of U.S. application Ser.\",\n \"No.\",\n \"14/230,494, filed Mar.\",\n \"31, 2014, which claims the benefit under 35 U.S.C.\",\n \"§§ 120 and 365(c) of PCT International Application No.\",\n \"PCT/US2012/057431, filed Sep. 27, 2012, and claiming benefit under 35 U.S.C.\",\n \"§ 119(e) of U.S.\",\n \"Provisional Application No.\",\n \"61/540,953, filed Sep. 29, 2011.The disclosures of U.S. application Ser.\",\n \"No.\",\n \"14/230,494, PCT International Application No.\",\n \"PCT/US2012/057431, and U.S.\",\n \"Provisional Application No.\",\n \"61/540,953 are incorporated herein by reference in their entirety.\",\n \"FIELD OF THE INVENTION This invention relates to compositions containing imidazole-based compounds, and optionally, colloidal oatmeal, and to methods of their use for the treatment, prevention, and management of symptoms, conditions, diseases, and disorders of the skin.\",\n \"SUMMARY OF THE INVENTION One aspect of the invention relates to a method of treating, managing, or preventing a dermatological or skin condition, which comprises topically administering to a subject in need thereof a therapeutically or prophylactically effective composition comprising an imidazole compound of the formula: wherein: R1 is hydrogen, alkyl or aryl; R6 is OR10 or OC(O)R10; R7 is OR11 or OC(O)R11; R8 is OR12 or OC(O)R12; and R9 is hydrogen, CH2OR13 or CH2OC(O)R13; and each of R10, R11, R12 and R13 is independently hydrogen or lower alkyl, and pharmaceutically, dermatologically, or cosmetically acceptable salts thereof.\",\n \"Another aspect of the invention relates to a method of caring for skin, which comprises topically administering to the skin of a subject in need thereof a composition comprising the imidazole compound in an amount and for a time sufficient to effect a change in the skin.\",\n \"Another aspect of the invention relates to a method of delivering or depositing a benefit agent onto skin, which comprises topically administering to the skin of a subject a composition comprising the imidazole compound contained in a dermatologically acceptable carrier.\",\n \"Another aspect of the invention relates to a method of suppressing a dermatologic immune response in a patient in need thereof, comprising topically administering an effective composition comprising the imidazole compound contained in a dermatologically acceptable carrier.\",\n \"Another aspect of the invention relates to a composition comprising an imidazole compound of the formula: wherein: R1 is hydrogen, alkyl or aryl; R6 is OR10 or OC(O)R10; R7 is OR11 or OC(O)R11; R8 is OR12 or OC(O)R12; and R9 is hydrogen, CH2OR13 or CH2OC(O)R13; and each of R10, R11, R12 and R13 is independently hydrogen or lower alkyl, and pharmaceutically, dermatologically, or cosmetically acceptable salts thereof.\",\n \"Another aspect of the invention relates to compositions containing combinations of imidazole-based compounds and, optionally, colloidal oatmeal, and to methods of their use for the treatment, prevention, and management of inflammatory or immune-mediated symptoms, conditions, diseases, and disorders of the skin.\",\n \"Another aspect of the invention relates to combinations of imidazole-based compounds and, optionally, colloidal oatmeal, and to methods of their use for the treatment, prevention, and management of various skin symptoms, conditions, diseases, and disorders.\",\n \"Another aspect of the invention relates to combinations of imidazole-based compounds and colloidal oatmeal and to methods of their use for the treatment, prevention, and management of atopic dermatitis, seborrheic dermatitis, contact dermatitis, cutaneous sarcoidosis, drug induced photosensitivity, fixed drug eruptions, id reactions, bullous skin diseases, discoid lupus erythematosus, subacute cutaneous lupus, alopecia areata, sea bathers eruptions, psoriasis, dyshidrotic eczema, and pompholyx.\",\n \"Another aspect of the invention relates to compositions and methods for treating inflammatory and/or immune-mediated dermatoses with imidazole-based compounds and combinations of imidazole-based compounds and colloidal oatmeal.\",\n \"Another aspect of the invention relates to care, supplement, and pharmaceutical compositions containing imidazole-based compounds, colloidal oatmeal, and other ingredients used to treat disorders of the skin, as well as to compositions suitable for use in personal care applications, and in particular skin care compositions, which effectively deliver and/or deposit various benefit agents into and onto the skin.\",\n \"Another aspect of the invention relates to compositions and methods for treating contact dermatitis.\",\n \"These and further aspects of the claimed invention will now be explained in more detail.\",\n \"DETAILED DESCRIPTION OF THE INVENTION Definitions Unless otherwise indicated, the term “alkyl” means a straight chain, branched and/or cyclic (“cycloalkyl”) hydrocarbon having from 1 to 20 (e.g., 1 to 10 or 1 to 4) carbon atoms.\",\n \"Alkyl moieties having from 1 to 4 carbons are referred to as “lower alkyl.” Examples of alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, t-butyl, isobutyl, pentyl, hexyl, isohexyl, heptyl, 4,4-dimethylpentyl, octyl, 2,2,4-trimethylpentyl, nonyl, decyl, undecyl and dodecyl.\",\n \"Cycloalkyl moieties may be monocyclic or multicyclic, and examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and adamantyl.\",\n \"Additional examples of alkyl moieties have linear, branched and/or cyclic portions (e.g., 1-ethyl-4-methyl-cyclohexyl).\",\n \"The term “alkyl” includes saturated hydrocarbons as well as alkenyl and alkynyl moieties.\",\n \"Unless otherwise indicated, the terms “manage,” “managing” and “management” encompass preventing the recurrence of the specified disease or disorder in a patient who has already suffered from the disease or disorder, and/or lengthening the time that a patient who has suffered from the disease or disorder remains in remission.\",\n \"The terms encompass modulating the threshold, development and/or duration of the disease or disorder, or changing the way that a patient responds to the disease or disorder.\",\n \"Unless otherwise indicated, the terms “prevent,” “preventing” and “prevention” contemplate an action that occurs before a patient begins to suffer from the specified disease or disorder, which inhibits or reduces the severity of the disease or disorder.\",\n \"In other words, the terms encompass prophylaxis.\",\n \"Unless otherwise indicated, a “prophylactically effective” means sufficient to prevent a disease or condition, or one or more symptoms associated with the disease or condition, or prevent its recurrence.\",\n \"A prophylactically effective amount of a compound means an amount of therapeutic agent, alone or in combination with other agents, which provides a prophylactic benefit in the prevention of the disease.\",\n \"The term “prophylactically effective” can encompass a composition that improves overall prophylaxis or enhances the prophylactic efficacy of another prophylactic agent.\",\n \"Unless otherwise indicated, a “therapeutically effective” means sufficient to provide a therapeutic benefit in the treatment or management of a disease or condition, or to delay or minimize one or more symptoms associated with the disease or condition.\",\n \"A therapeutically effective amount of a compound means an amount of therapeutic agent, alone or in combination with other therapies, which provides a therapeutic benefit in the treatment or management of the disease or condition.\",\n \"The term “therapeutically effective” can encompass a composition that improves overall therapy, reduces or avoids symptoms or causes of a disease or condition, or enhances the therapeutic efficacy of another therapeutic agent.\",\n \"Unless otherwise indicated, the terms “treat,” “treating” and “treatment” contemplate an action that occurs while a patient is suffering from the specified disease or disorder, which reduces the severity of the disease or disorder, or retards or slows the progression of the disease or disorder.\",\n \"Unless otherwise indicated, the term “include” has the same meaning as “include, but are not limited to,” and the term “includes” has the same meaning as “includes, but is not limited to.” Similarly, the term “such as” has the same meaning as the term “such as, but not limited to.” Unless otherwise indicated, one or more adjectives immediately preceding a series of nouns is to be construed as applying to each of the nouns.\",\n \"For example, the phrase “optionally substituted A, B, or C” has the same meaning as “optionally substituted A, optionally substituted B, or optionally substituted C.” It should be noted that a chemical moiety that forms part of a larger compound may be described herein using a name commonly accorded it when it exists as a single molecule or a name commonly accorded its radical.\",\n \"It should also be noted that if the stereochemistry of a structure or a portion of a structure is not indicated with, for example, bold or dashed lines, the structure or the portion of the structure is to be interpreted as encompassing all stereoisomers of it.\",\n \"Moreover, any atom shown in a drawing with unsatisfied valences is assumed to be attached to enough hydrogen atoms to satisfy the valences.\",\n \"As used herein, the term “benefit agent” includes any active ingredient that is to be delivered into and/or onto the skin at a desired location, such as a cosmetic, care or pharmaceutical agent, and that is capable of providing a cosmetic, care, or therapeutic effect.\",\n \"By “cosmetic agent,” it is meant any ingredient that is appropriate for cosmetically treating, providing nutrients to, and/or conditioning the hair, nail, and/or skin via topical application.\",\n \"By “pharmaceutical agent,” it is mean any drug that is either hydrophobic or hydrophilic in nature and appropriate for topical use.\",\n \"As used herein “medicament agents” include those agents capable of promoting recovery from injury and illness.\",\n \"As used herein “pharmaceutically, dermatologically, or cosmetically acceptable” means that the ingredients which the term describes are suitable for use in contact with the skin without undue toxicity, incompatibility, instability, irritation, allergic response, and the like.\",\n \"Other than where otherwise indicated, or where required to distinguish over the prior art, all numbers expressing quantities of ingredients herein are to be understood as modified in all instances by the term “about”.\",\n \"As used herein, the words “may” and “may be” are to be interpreted in an open-ended, non-restrictive manner.\",\n \"At minimum, “may” and “may be” are to be interpreted as definitively including, but not limited to, the composition, structure, or act recited.\",\n \"As used herein, and in particular as used herein to define the elements of the claims that follow, the articles “a” and “an” are synonymous and used interchangeably with “at least one” or “one or more,” disclosing or encompassing both the singular and the plural, unless specifically defined herein otherwise.\",\n \"The conjunction “or” is used herein in both in the conjunctive and disjunctive sense, such that phrases or terms conjoined by “or” disclose or encompass each phrase or term alone as well as any combination so conjoined, unless specifically defined herein otherwise.\",\n \"The description of a group or class of materials as suitable or preferred for a given purpose in connection with the invention implies that mixtures of any two or more of the members of the group or class are equally suitable or preferred.\",\n \"Description of constituents in chemical terms refers unless otherwise indicated, to the constituents at the time of addition to any combination specified in the description, and does not necessarily preclude chemical interactions among the constituents of a mixture once mixed.\",\n \"Steps in any method disclosed or claimed need not be performed in the order recited, except as otherwise specifically disclosed or claimed.\",\n \"Changes in form and substitution of equivalents are contemplated as circumstances may suggest or render expedient.\",\n \"Although specific terms have been employed herein, such terms are intended in a descriptive sense and not for purposes of limitation.\",\n \"Methods of Treatment The general form of treatment for dermatoses according to the invention is chemical therapy by topical administration of the benefit agent or agents.\",\n \"Topical medications may be delivered to the affected site by means including but not limited to baths, soaps, shampoos, wet dressings or soaks, powders, pastes, tinctures, shake lotions, aerosols, foams, medicated tape, transdermal devices, creams, ointments, oils, and emulsions.\",\n \"Generally, the composition is topically applied to the affected skin areas in a predetermined or as-needed regimen to bring about improvement, it generally being the case that gradual improvement is noted with each successive application.\",\n \"Insofar as has been determined based upon studies to date, no adverse side effects are encountered.\",\n \"In treating atopic dermatitis, psoriasis, eczema, or any of the conditions or indications disclosed herein, an ointment or lotion according to aspects of the invention containing 0.01% to 10% by weight of the imidazole compound and, optionally, 0.01% to 25% of colloidal oatmeal is applied to the affected area of the skin.\",\n \".\",\n \"The upper limit of the imidazole compound may preferably be 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2.5%, 2%, or even 1.5% by weight of the ointment or lotion, and the lower limit of the imidazole compound may preferably be 0.01%, 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, or even 0.5% by weight of the ointment or lotion.\",\n \"Preferably the ointment or lotion comprises 1.0% by weight of the imidazole compound.\",\n \"The upper limit of the colloidal oatmeal may preferably be 25%, 20%, 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2.5%, 2%, or even 1.5% by weight of the ointment or lotion, and the lower limit of the colloidal oatmeal may preferably be 0.01%, 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, or even 0.5% by weight of the ointment or lotion.\",\n \"Preferably the ointment or lotion comprises 1.0% by weight of the colloidal oatmeal.\",\n \"The patient may be treated, for example, daily for two to four weeks with a dosage amount of 5 mg to 10 mg of imidazole compound and 5 mg to 10 mg of colloidal oatmeal a day.\",\n \"The topically effective amounts of imidazole compound are typically 0.5% to 2% by weight and of the colloidal oatmeal 0.5%% to 2% by weight in an ointment or lotion and are applied one to three times a day for a period of time, typically weeks, to effectively treat the dermatoses.\",\n \"Under certain circumstances, it is desirable to administer the imidazole compound and colloidal oatmeal simultaneously with other dermatologically active agents.\",\n \"The precise amount of imidazole compound and colloidal oatmeal used alone or with other dermatologic agents varies depending, for example, on the condition for which the composition is administered.\",\n \"The amount, route of administration and dosing schedule will depend upon factors such as the specific indication to be treated, prevented, or managed, and the age, sex and condition of the patient.\",\n \"The roles played by such factors are well known in the art, and may be accommodated by routine experimentation.\",\n \"One skilled in the art can adjust the dosage forms to achieve the desired therapeutic levels.\",\n \"Depending on the specific tissue to be treated, additional components may be used prior to, in conjunction with, or subsequent to treatment with active ingredients of the invention.\",\n \"For example, penetration enhancers may be used to assist in delivering active ingredients to the tissue.\",\n \"Another embodiment of the present invention is directed to a method for depositing a benefit agent onto the skin to a desired location on a human or animal.\",\n \"While the frequency and amount of the benefit agent-containing composition to be applied will depend upon, for example, the type and amount of benefit agent available, the intended usage of the final composition, i.e.\",\n \"therapeutic versus maintenance regimen, and the sensitivity of the individual user to the composition, typically the benefit agent-containing composition of the present invention should be topically applied to affected body parts at regular intervals, and preferably twice daily, in the morning and evening.\",\n \"The composition may be applied more frequently during the initial stages of treatment, until the desired effect is achieved, then less frequently when maintenance is desired.\",\n \"Conditions Treated The methods according to the invention can be used to treat a variety of skin conditions, which result in inflammation or erythema.\",\n \"For example, inflammation or erythema can result from external causes such as sun or wind burn or irritating soaps or cleansers.\",\n \"It is also known that inflammation and erythema can be caused from inherent conditions such as rosacea, atopic dermatitis, or allergic skin reactions.\",\n \"The method according to the invention can be used to treat inflammation and/or erythema caused by both external and inherent conditions.\",\n \"Another aspect of the invention relates to combinations of imidazole-based compounds and colloidal oatmeal and to methods of their use for the treatment, prevention, and management of atopic dermatitis, seborrheic dermatitis, contact dermatitis, cutaneous sarcoidosis, drug induced photosensitivity, fixed drug eruptions, id reactions, bullous skin diseases, discoid lupus erythematosus, subacute cutaneous lupus, alopecia areata, sea bathers eruptions, psoriasis, dyshidrotic eczema, and Pompholyx.\",\n \"This list of examples of dermatological conditions, for which the therapy as proposed in this application is useful, does not limit the present invention to these indications, since there may be other dermatological conditions not mentioned here where combinations of imidazole-based compounds and colloidal oatmeal may also be effective.\",\n \"Thus, further non-limiting examples of conditions to which the present invention may be applied include: (a) dermatologic allergies, such as contact dermatitis, photoallergic dermatitis; industrial dermatoses caused by exposure to a variety of compounds used by industry that are contact irritants; atopic eczema (infantile and adult), dermatoses caused by drugs and nummular eczema; (b) immune-mediated skin diseases, suchbullous pemphigoid, pemphigus vulgaris, necrotizing vasculitis, lupus erythematosus (discoid and systemic), dermatitis herpetiformis; (B2) immune, non-immune, or autoimmune urticarias such as allergic urticaria, chronic idiopathic urticaria, solar urticaria, cholinergic urticaria, pressure urticaria, cold urticaria, dermatographia, and pruritic urticarial papules and plaques of pregnancy (PUPPP); (B3) mastocytosis; (c) pruritic dermatoses, such as winter, senile, and essential pruritus, pruritus ani, external otitis, and genital pruritus; (d) vascular dermatoses, such as erythema multiforme, erythema nodosum, stasis dermatitis, purpuric dermatoses such as thrombocytopenic purpura and Henoch-Schonlein purpura, ecchymoses, stasis purpura, primary and secondary telangiectases; (e) seborrheic dermatitis, acne, and rosacea; (f) papulosquamous dermatoses: such as psoriasis, pityriasis rosea, lichen planus; (g) bacterial dermatoses, such as pyoderma, impetigo, ecthyma, folliculitis, furuncles styes, carbuncles, sweat gland infections, erysipelas, erythrasma, infected ulcers, and infected eczematoid dermatitis; (h) systemic bacterial infections with skin manifestations, such as scarlet fever, granuloma inguinale, chancroid, tuberculosis, leprosy, gonorrhea, rickettsial diseases, actinomycosis, syphilis; (i) viral skin infection, such as those caused by herpes simplex virus, Kaposi's varicelliform eruption, zoster, chickenpox, smallpox, vaccinia, cowpox, warts, molluscum contagiosum, lymphogranuloma venereum, exanthematous diseases such as German measles, roseola and erythema infectiosum; (j) mycolic skin infections, such as tinea (superficial fungal infections of the skin in various body sites), sporotrichosis, North American blastomycosis; (k) granulomatous dermatoses, such as sarcoidosis, granuloma annulare, silica induced granulomas; (1) parasitic skin infections, such as scabies, pediculosis; (m) bullous dermatoses; (n) exfoliative dermatitis, primary and secondary; (o) pigmented dermatoses, such as chloasma (melasma) and vitiligo; (p) collagen diseases, such as lupus erythematosus, scleroderma, dermatomyositis; (q) dermatoses due to internal diseases, such as Kaposi's sarcoma, pyoderma gangrenosum associated with ulcerative colitis, ulcers due to diabetes, xanthomas; (r) diseases of mucous membranes, such as aphthous ulcers; (s) dermatoses due to physical agents, such as sunburns and radiation; and (t) photosensitive dermatoses of the exogenous-type, such as drug-induced photodermatitis, contact dermatitis with photoallergic components, and of the endogenous-type, such as porphyrias, collagen vascular disorders such as lupus erythematosus, dermatomyositis, and polymorphous light eruptions.\",\n \"Contact dermatitis is a steroid responsive condition and is caused by plant saps (poison ivy, etc) and chemicals.\",\n \"About 80% are irritant type while 20% are allergic.\",\n \"There are over 85,000 chemicals estimated to exist in the modern environment.\",\n \"Any might cause contact dermatitis.\",\n \"The most common allergic sensitizers are nickel sulfate, fragrances, thimerosal, quartemium-15, neomycin sulfate, formaldehyde, bacitracin, thiuram mix, balsam of Peru, cobalt chloride, p-phenylenediamine, and carba mix.\",\n \"Other steroid responsive dematoses might include seborrheic dermatitis, diaper rash, and bullous skin diseases such as bullous pemphigoid.\",\n \"Further examples of diseases and disorders include ankylosing spondylitis, asthma (e.g., bronchial asthma), atopic dermatitis, Behcet's disease, graft-vs-host disease, Kawasaki syndrome, lupus erythematosus, multiple sclerosis, myasthenia gravis, pollinosis, psoriasis, psoriatic arthritis, rheumatoid arthritis, scleroderma, transplant rejection (e.g., of organ, cell or bone marrow), type 1 diabetes, and uveitis.\",\n \"Additional diseases and disorders include Addison's Disease, anti-phospholipid syndrome, autoimmune atrophic gastritis, achlorhydra autoimmune, Celiac Disease, Crohn's Disease, Cushing's Syndrome, dermatomyositis, Goodpasture's Syndrome, Grave's Disease, Hashimoto's thyroiditis, idiopathic adrenal atrophy, idiopathic thrombocytopenia, Lambert-Eaton Syndrome, pemphigoid, pemphigus vulgaris, pernicious anemia, polyarteritis nodosa, primary biliary cirrhosis, primary sclerosing cholangitis, Raynauds, Reiter's Syndrome, relapsing polychondritis, Schmidt's Syndrome, Sjogren's Syndrome, sympathetic ophthalmia, Takayasu's Arteritis, temporal arteritis, thyrotoxicosis, ulcerative colitis, and Wegener's granulomatosis.\",\n \"Further indications addressed by the compositions and methods of the invention include, for example, immunosuppression (e.g., employing one or more agents such as cyclosporin A, QKT3, FK506, mycophenolate mofetil (MMF), azathioprine, corticosteroids (such as prednisone), antilymphocyte globulin, antithymocyte globulin, and the like), inflammatory disease therapy (e.g., employing disease-modifying agents (such as antimalarials, methotrexate, sulfasalazine, mesalamine, azathioprine, 6-mercaptopurine, metronidazole, injectable and oral gold, D-penicillamine, and the like), corticosteroids, non-steroidal antiinflammatory drugs (such as aspirin, sodium salicylate, magnesium salicylate, choline magnesium salicylate, salicylsalicylic acid, ibuprofen, naproxen, diclofenac, diflunisal, etodolac, fenoprofen calcium, fluriprofen, piroxicam, indomethacin, ketoprofen, ketorolac tromethamine, meclofenamate, meclofenamate sodium, mefenamic acid, nabumetone, oxaprozin, phenyl butyl nitrone (PBN), sulindac, tolmetin, and the like), and the like), anti-cancer therapy (e.g., employing one or more agents such as alkylating agents (such as mechlorethamine, chlorambuccil, ifosfamide, melphalan, busulfan, carmustine, lomustine, procarbazine, dacarbazine, cisplatin, carboplatin, and the like), antimetabolites (such as methotrexate, mercaptopurine, thioguanine fluorouracil, cytarabine, and the like), hormonal agents (such as testosterone propionate, fluoxymesterone, flutamide, diethylstilbestrol, ethinyl estradiol, tamoxifen, hydroxyprogesterone caproate, medroxyprogesterone, megestrol acetate, and the like), adrenocorticosteroids (such as prednisone), aromatase inhibitors (such as amino glutethimide), leuprolide, goserelin acetate, biological response modifiers (such as interferon-.alpha.2a, interferon-.alpha.2b, interleukin-2, and the like), peptide hormone inhibitors (such as octreotide acetate), natural products (such as vinblastine, vincristine, vinorelbine, paclitaxel, dactinomycin, daunorubicin, idarubicin, doxorubicin, etoposide, plicamycin, mitomycin, mitoxantrone, bleomycin, hydroxyurea, mitotane, fludarabine, cladribine, and the like), supportive agents (such as allopurinol, mesna, leucovorin, erythropoietin, filgrastim, sargramostim, and the like), and the like, anti-microbial therapy (e.g., employing one or more agents such as celftriaxone, TMP-SMZ, penicillin, aminoglycosides, vancomycin, gentamicin, rifampin, imipenem, clindamycin, metronidazole, tetracycline, erythromycin, sulfonamide, streptomycin, ampicillin, isoniazid, pyrazinamide, ethambutol, and the like), anti-fungal therapy (e.g., employing agents such as amphotericin B, griseofulvin, myastatin, flucytosine, natamycin, antifungal imidazoles (e.g., clotrimazole, miconazole, ketoconazole, fluconazole, itraconazole, and the like), and the like, anti-retroviral therapy (e.g., employing agents such as protease inhibitors (such as Invirase, Ritonavir, Crixivan, and the like), zidovudine, didanosine, zalcitabine, stavudine, viramune, and the like), and treatment of cellular proliferative diseases (e.g., oncolytic viral therapy employing naturally occurring and/or modified oncolytic viruses such as reovirus, adenovirus, seneca valley virus, vesicular stomatitis virus, poliovirus, vacina virus, herpes virus and the like), and treatment of opportunistic infections and malignancies (e.g., anti-AIDS treatment, employing agents such as pentamidine, trimethoprim/sulfamethoxazole, primaquine, atovaquope, clarithromycin, clofazimine, ethambutol, rifampin, amikacin, ciprofloxacin, pyrimethamine, amphotericin B, ganciclovir, foscarnet, fluconazole, ketoconazole, acyclovir, and the like).\",\n \"Benefit Agents A first element of the compositions and methods according to aspects of the invention is an imidazole compound of the formula: wherein: R1is hydrogen, alkyl or aryl; R6 is OR10 or OC(O)R11; R7 is ORH or OC(O)R11; R8 is OR12 or OC(O)R12; and R9 is hydrogen, CH2OR13 or CH2OC(O)R13; and each of R10, R11, R12 and R13 is independently hydrogen or lower alkyl.\",\n \"The compounds of the preceding formula of the present invention may also be present in the form of pharmaceutically, dermatologically, or cosmetically acceptable salts thereof that can be made by conventional techniques.\",\n \"Pharmaceutically, dermatologically, or cosmetically acceptable acidic/anionic salts include, and are not limited to acetate, benzenesulfonate, benzoate, bicarbonate, bitartrate, bromide, calcium edetate, camsylate, carbonate, chloride, citrate, dihydrochloride, edetate, edisylate, estolate, esylate, fumarate, glyceptate, gluconate, glutamate, glycollylarsanilate, hexylresorcinate, hydrabamine, hydrobromide, hydrochloride, hydroxynaphthoate, iodide, isethionate, lactate, lactobionate, malate, maleate, mandelate, mesylate, methylbromide, methylnitrate, methylsulfate, mucate, napsylate, nitrate, pamoate, pantothenate, phosphate/diphospate, polygalacturonate, salicylate, stearate, subacetate, succinate, sulfate, tannate, tartrate, teoclate, tosylate and triethiodide.\",\n \"Pharmaceutically, dermatologically, or cosmetically acceptable basic/cationic salts include, and are not limited to aluminum, benzathine, calcium, chloroprocaine, choline, diethanolamine, ethylenediamine, lithium, magnesium, meglumine, potassium, procaine, sodium and zinc.\",\n \"Other salts may, however, be useful in the preparation of compounds according to this invention or of their cosmetically acceptable salts.\",\n \"Organic or inorganic acids also include, and are not limited to, hydriodic, perchloric, sulfuric, phosphoric, propionic, glycolic, methanesulfonic, hydroxyethanesulfonic, oxalic, 2-naphthalenesulfonic, p-toluenesulfonic, cyclohexanesulfamic, saccharinic or trifluoroacetic acid.\",\n \"In particular embodiments, the imidazole compound is 2-acetyl-4-tetrahydroxybutylimidazole (THI).\",\n \"THI is a component of caramel color III and has been identified as a sphingosine-1-phosphate lyase antagonist.\",\n \"Sphingosine-1-phosphate (SIP) is a bioactive molecule with effects on multiple organ systems.\",\n \"Sphingosine-1-phosphate lyase is a vitamin B6-dependent enzyme localized in the membrane of the endoplasmic reticulum.\",\n \"Van Veldhoven and Mannaerts, J. Biol.\",\n \"Chem.\",\n \"266:12502-12507 (1991); Van Veldhoven and Mannaerts, Adv.\",\n \"Lipid.\",\n \"Res.\",\n \"26:69 (1993).\",\n \"The polynucleotide and amino acid sequences of human SP1 lyase and its gene products are described in PCT Patent Application No.\",\n \"WO 99/16888.THI inhibits S1P lyase activity when administered to mice.\",\n \"Schwab, S. et al., Science 309:1735-1739 (2005).\",\n \"Administration of the compound to rats and mice induces lymphopenia and causes the accumulation of mature T cells in the thymus.\",\n \"See, e.g., Schwab, supra; Pyne, S. G., ACGC Chem.\",\n \"Res.\",\n \"Comm.\",\n \"11:108-112 (2000); Gugasyan, R., et al., Immunology 93(3):398-404 (1998); Halweg, K. M. and Büchi, G., J. Org.\",\n \"Chem.\",\n \"50:1134-1136 (1985); U.S. Pat.\",\n \"No.\",\n \"4,567,194 to Kroeplien and Rosdorfer.\",\n \"Still, there are no known reports of THI having an immunological effect in animals other than mice and rats.\",\n \"Although U.S. Pat.\",\n \"No.\",\n \"4,567,194 alleges that THI and some related compounds may be useful as immunosuppressive medicinal agents, studies of the compound in humans have found no immunological effects.\",\n \"See Thuvander, A. and Oskarsson, A., Fd.\",\n \"Chem.\",\n \"Toxic.\",\n \"32(1):7-13 (1994); Houben, G. F., et al., Fd.\",\n \"Chem.\",\n \"Toxic.\",\n \"30(9):749-757 (1992).\",\n \"Compounds of the invention may contain one or more stereocenters, and can exist as racemic mixtures of enantiomers or mixtures of diastereomers.\",\n \"This invention encompasses stereomerically pure forms of such compounds, as well as mixtures of those forms.\",\n \"Stereoisomers may be asymmetrically synthesized or resolved using standard techniques such as chiral columns or chiral resolving agents.\",\n \"See, e.g., Jacques, J., et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Wilen, S. H., et al., Tetrahedron 33:2725 (1977); Eliel, E. L., Stereochemistry of Carbon Compounds (McGraw Hill, NY, 1962); and Wilen, S. H., Tables of Resolving Agents and Optical Resolutions, p. 268 (E. L. Eliel, Ed., Univ.\",\n \"of Notre Dame Press, Notre Dame, Ind., 1972).\",\n \"This invention further encompasses stereoisomeric mixtures of compounds disclosed herein.\",\n \"It also encompasses configurational isomers of compounds disclosed herein, either in admixture or in pure or substantially pure form.\",\n \"Compounds of the invention can be prepared by methods known in the art (e.g., by varying and adding to the approaches described in Pyne, S. G., ACGC Chem.\",\n \"Res.\",\n \"Comm.\",\n \"11:108-112 (2000); Halweg, K. M. and Büchi, G., J. Org.\",\n \"Chem.\",\n \"50:1134-1136 (1985)).\",\n \"Compounds can also be made by the methods disclosed below and variants thereof, which will be apparent to those of ordinary skill in the art.\",\n \"The compositions according to the invention preferably contain the imidazole-based compound in an amount of 0.001% to 10%, more preferably 0.5% to 2%, and most preferably about 1% by weight of the composition.\",\n \"The imidazole-based compound may also preferably be included in an amount of 0.01% to 10%, 0.1% to 10%, 0.1% to 9%, 0.1% to 8%, 0.1% to 7%, 0.1% to 6%, 0.1% to 5%, 0.2% to 5%, 0.3% to 5%, 0.4% to 5%, 0.5% to 5%, 0.5% to 4%, and 0.5% to 3% by weight of the composition.\",\n \"A further element of preferred compositions and methods according to aspects of the invention is colloidal oatmeal.\",\n \"Oatmeal has been used as a soothing agent to relieve itch and irritation associated with various xerotic dermatoses.\",\n \"In 1945, a ready to use colloidal oatmeal, produced by finely grinding the oat and boiling it to extract the colloidal material, became available.\",\n \"Today, colloidal oatmeal is available in various dosage forms from powders for the bath to shampoos, shaving gels, and moisturizing creams.\",\n \"Currently, the use of colloidal oatmeal as a skin protectant is regulated by the U.S. Food and Drug Administration (FDA) according to the Over-The-Counter Final Monograph for Skin Protectant Drug Products issued in June 2003.Its preparation is also standardized by the United States Pharmacopeia.\",\n \"The many clinical properties of colloidal oatmeal derive from its chemical polymorphism.\",\n \"The high concentration in starches and beta-glucan is responsible for the protective and water-holding functions of oat.\",\n \"The presence of different types of phenols confers antioxidant and anti-inflammatory activity.\",\n \"Some of the oat phenols are also strong ultraviolet absorbers.\",\n \"The cleansing activity of oat is mostly due to saponins.\",\n \"Its many functional properties make colloidal oatmeal a cleanser, moisturizer, buffer, as well as a soothing and protective anti-inflammatory agent.\",\n \"Colloidal oatmeal may act at the site of application to control the osmotic pressure of water with respect to the skin and permits adequate water to enter into the stratum corneum.\",\n \"Oatmeal may leave an occlusive film on the skin that serves to hold in moisture, which protects the skin against irritation and acts as an antipruritic.\",\n \"Colloidal oatmeal includes the powder resulting from the grinding and further processing of whole oat grain meeting United States Standards for Number 1 or Number 2 oats.\",\n \"A suitable colloidal oatmeal has a particle size distribution as follows: not more than 3 percent of the total particles exceed 150 micrometers in size and not more than 20 percent of the total particles exceed 75 micrometers in size.\",\n \"Examples of suitable colloidal oatmeals include, but are not limited to, “Tech-O” colloidal oatmeals (e.g., Tech-O #11-065 colloidal oatmeal) available from the Beacon Corporation and colloidal oatmeals available from Quaker.\",\n \"A USP grade of colloidal oatmeal suitable for use in this invention may be obtained under the mark “Tech-O” from Beacon CMP Corporation, 611 Springfield Road, Kenilworth, N.J. 07033.The compositions may further contain one or more benefit agents or pharmaceutically-acceptable salts thereof.\",\n \"The benefit agents useful herein may be categorized by their therapeutic benefit or their postulated mode of action.\",\n \"However, it is to be understood that the benefit agents useful herein may, in some circumstances, provide more than one therapeutic benefit or operate via greater than one mode of action.\",\n \"Therefore, the particular classifications provided herein are made for the sake of convenience and are not intended to limit the benefit agents to the particular application(s) listed.\",\n \"In addition, the compounds, which are identified below as being suitable for use as benefit agents, may be used in an amount over and above the amount that they may be used for other purposes in the compositions of the invention.\",\n \"Further benefit agents useful in the methods and compositions of the invention include antipruritics, emollients, antiseptics, antifungals, antiinflammatories, immunosuppressants, psoriasis agents, anti-cancer agents, antibiotics, antiparasitics, antioxidants, antibacterials, antimicrobials, antiretrovirals, moisturizers, sunscreens, NSAIDs, hormones, steroids, analgesics, antihistamines, and antipyretics.\",\n \"The following chemotherapeutic agents used to treat dermatoses are not comprehensive but rather consist of examples of commonly used groups of drugs.\",\n \"The antihistamines added to the topical compositions are typically from the structural classes of ethylenediamines, aminoalkylethers, and alkylamines.\",\n \"Among the ethylenediamine group are such antihistamines as antazoline phosphate, clemizole hydrochloride, chlorcyclizine hydrochloride, chlorothen, methapheniline hydrochloride, dorastine hydrochloride, methdilazine hydrochloride, promethazine hydrochloride, pyrathiazine hydrochloride, pyrilamine maleate, quinetolate, thenaldine, thenyldiamine hydrochloride, thonzylamine hydrochloride, tripelennamine, and zolamine hydrochloride.\",\n \"Among the aminoalkylether group are such antihistamines as chlorphenoxamine hydrochloride, carbinoxamine maleate, clemastine, diphenhydramine hydrochloride, diphenylpyraline hydrochloride, doxylamine succinate, and pyroxamine maleate.\",\n \"Among the alkamine group are such antihistamines as azatadine maleate, bromdiphenhydramine hydrochloride, cyproheptadine hydrochloride, dimethindene maleate, phenindamine tartrate, pheniramine maleate, brompheniramine maleate, dexbrompheniramine maleate, chlorpheniramine maleate, dex-chlorpheniramine maleate, closiramine, cycliramine maleate, mianserin hydrochloride, pyrrobutamine phosphate, terfenadine, and triprolidine hydrochloride.\",\n \"Besides the above, some compositions in structural groups, which groups are not primarily antihistamines such as phenothiazines, piperidines, and piperazines, have antihistaminic characteristics.\",\n \"These groups include promethazine, astemizole, fexofenadine, loratadine, desloratadine, terfenadine, cetirizine, and meclizin, which are antihistaminic.\",\n \"Another active ingredient used in the formulations hereof is the employment of a topical anesthetic.\",\n \"While some of these topical anesthetic compounds are structurally related to the antihistamines in the preceding paragraph, the compounds take on a disinct role in preparations described.\",\n \"The first group are esters of benzoic acid and diethylaminoethyl alcohols, namely, benzocaine, chloroprocaine, procaine, and tetracaine.\",\n \"Other synthetic anesthetic compounds, which are not esters of benzoic acid and are pharmacologically grouped together, are bupivacaine, dibucaine, lidocaine, mepivacaine, and prilocaine.\",\n \"Besides these two groups, the compounds of etidocaine and pramoxine are also applicable.\",\n \"In one of the topical spray formulations described below the anesthetic, pramoxine hydrochloride, comprises up to 1.0 percent by weight thereof.\",\n \"Corticosteroids are a group of agents used to treat inflammation of the skin having many different etiologies.\",\n \"Examples of indications in which systemically administered corticosteroids are employed as therapeutics include psoriasis, erythema nodosum leprosum, discold lupus erythematosus, urticaria, different types of pruritis, pemphigus and keloids.\",\n \"Antihistamines are a group of agents having an antipruritic effect.\",\n \"They include alkylamines, phenothiazines, ethylenediamine, ethanolamine, and piperazine.\",\n \"Retinoids are synthetic and natural forms of vitamin A, including isotretinoin and etretinate.\",\n \"Retinoids are used to treat acne vulgaris or rosacea and psoriasis.\",\n \"Antimicrobial compounds include antibiotic, antibacterial, antifungal, antiviral, and antiparasitic agents.\",\n \"In addition to the imidazole-based compound and colloidal oatmeal, the benefit agents comprising topical preparations used according to the invention may also comprise: (a) anti pruritic agents, which relieve itching, such as 0.25% menthol, 0.5% phenol, 2% camphor and 2-10% coal tar solutions; (b) keratoplastic agents, which increase the thickness of the horny layer of the skin, such as 1-2% salicylic acid; (c) emollients, which often soften surface layers of skin, such as petrolatum, nivea oil and mineral oil; (d) antiseptics, which inhibit and/or destroy fungi and/or bacteria, such as 3% Vioform, 3-10% ammoniated mercury, antifungal agents such as Whitfields ointment, antibiotics such as 3% terramycin, 0.5% neomycin, 0.1% garamycin and 3% aureomycin; (e) antieczematous agents, which remove oozing and vesicular excretions, such as Burows solution, soaks or packs, 2-5% coal tar solutions and 0.5-2% hydrocortisone; (f) keratolytic agents, which remove or soften the horny layer of the skin, such as 4-10% salicylic acid, 2-4% resorcinol and 4-10% sulfur; and (g) antiparasitics, which inhibit or destroy infestations by parasites, such as Kewell cream for scabies and pediculosis and Eurax lotion for scabies.\",\n \"Further examples of suitable benefit agents include, but are not limited to: depigmentation agents; reflectants; film forming polymers; humectants; amino acids and their derivatives; antimicrobial agents; allergy inhibitors; anti-acne agents; anti-aging agents; anti-wrinkling agents, antiseptics; analgesics; antitussives; antipruritics; local anesthetics; anti-hair loss agents; hair growth promoting agents; hair growth inhibitor agents, antihistamines such as Mandragora Vernalis, Tanacetum Parthenium and the like; antiinfectives such as Acacia Catechu, Aloe Barbadensis, Convallaria Maj alis, Echinacea, Eucalyptus, Mentha Piperita, Rosa Canina, Sassafras Albidum, and the like; inflammation inhibitors; anti-emetics; anticholinergics; vasoconstrictors; vasodilators; wound healing promoters; peptides, polypeptides and proteins; deodorants and anti-perspirants; medicament agents; skin emollients and skin moisturizers; skin firming agents, hair conditioners; hair softeners; hair moisturizers; vitamins; tanning agents; skin lightening agents; antifungals such as Centaurea Cyanus, Kalmia Latifolia and antifungals for foot preparations; depilating agents; shaving preparations; external analgesics; perfumes; counterirritants; hemorrhoidals; insecticides; poison ivy products; poison oak products; burn products; anti-diaper rash agents; prickly heat agents; make-up preparations; vitamins; amino acids and their derivatives; herbal extracts; retinoids; flavenoids; sensates; anti-oxidants; skin conditioners; hair tighteners; chelating agents; cell turnover enhancers; coloring agents; pigments; sunscreens; anti-edema agents; collagen enhancers; and mixtures thereof.\",\n \"Examples of suitable anti-edema agents nonexclusively include bisabolol natural, synthetic bisabolol, and mixtures thereof.\",\n \"Examples of suitable vasoconstrictors nonexclusively include horse chestnut extract, prickly ash, and mixtures thereof.\",\n \"Examples of suitable anti-inflammatory agents nonexclusively include benoxaprofen, centella asiatica, bisabolol, feverfew (whole), feverfew (parthenolide free), green tea extract, green tea concentrate, hydrogen peroxide, lycopene including “Lyc-o-Pen” available from LycoRed Natural Products Industries, Ltd., oat oil, chamomile, and mixtures thereof.\",\n \"Examples of collagen enhancers nonexclusively include vitamin A, vitamin C, and mixtures thereof.\",\n \"Examples of suitable skin firming agent nonexclusively include dimethylaminoethanol (“DMAE”).\",\n \"Examples of suitable antipruritics and skin protectants nonexclusively include betaglucan, feverfew, soy and derivatives thereof, bicarbonate of soda, colloidal oatmeal, surfactant based colloidal oatmeal cleanser, Anagallis Arvensis, Oenothera Biennis, Verbena Officinalis, and the like.\",\n \"Examples of suitable reflectants nonexclusively include mica, alumina, calcium silicate, glycol dioleate, glycol distearate, silica, sodium magnesium fluorosilicate, and mixtures thereof.\",\n \"Suitable film forming polymers include those that, upon drying, produce a substantially continuous coating or film on the skin.\",\n \"Nonexclusive examples of suitable film forming polymers include acrylamidopropyl trimonium chloride/acrylamide copolymer; corn starch/acrylamide/sodium acrylate copolymer; polyquatemium-10; polyquaternium-47; polyvinylmethylether/maleic anhydride copolymer; styrene/acrylates copolymers; and mixtures thereof.\",\n \"Commercially available humectants which are capable of providing moisturization and conditioning properties to the composition are suitable for use in the present invention.\",\n \"Examples of suitable humectants nonexclusively include: water soluble liquid polyols selected from the group comprising glycerine, propylene glycol, hexylene glycol, butylene glycol, pentylene glycol, dipropylene glycol, and mixtures thereof; polyalkylene glycols; polyethylene glycol ether of methyl glucose; urea; fructose; glucose; honey; lactic acid; maltose; sodium glucuronate; and mixtures thereof.\",\n \"Suitable amino acid agents include amino acids derived from the hydrolysis of various proteins as well as the salts, esters, and acyl derivatives thereof.\",\n \"Examples of such amino acid agents nonexclusively include amphoteric amino acids such as alkylamido alkylamines, i.e.\",\n \"stearyl acetyl glutamate, capryloyl silk amino acid, capryloyl collagen amino acids; capryloyl keratin amino acids; capryloyl pea amino acids; cocodimonium hydroxypropyl silk amino acids; corn gluten amino acids; cysteine; glutamic acid; glycine; hair keratin amino acids; amino acids such as aspartic acid, threonine, serine, glutamic acid, proline, glycine, alanine, cystine, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, cysteic acid, lysine, histidine, arginine, cysteine, tryptophan, citrulline; lysine; silk amino acids, wheat amino acids; and mixtures thereof.\",\n \"Suitable proteins include those polymers that have a long chain, i.e.\",\n \"at least about 10 carbon atoms, and a high molecular weight, i.e.\",\n \"at least about 1000, and are formed by self-condensation of amino acids.\",\n \"Nonexclusive examples of such proteins include collagen, deoxyribonuclease, iodized corn protein; milk protein; protease; serum protein; silk; sweet almond protein; wheat germ protein; wheat protein; alpha and beta helix of keratin proteins; hair proteins, such as intermediate filament proteins, high-sulfur proteins, ultrahigh-sulfur proteins, intermediate filament-associated proteins, high-tyrosine proteins, high-glycine tyrosine proteins, tricohyalin, and mixtures thereof.\",\n \"Examples of suitable vitamins nonexclusively include vitamin B complex; including thiamine, nicotinic acid, biotin, pantothenic acid, choline, riboflavin, vitamin B6, vitamin B12, pyridoxine, inositol, carnitine; vitamins A, C, D, E, K and their derivatives such as vitamin A palmitate and pro-vitamins, e.g.\",\n \"(i.e.\",\n \"panthenol (pro vitamin B5) and panthenol triacetate) and mixtures thereof.\",\n \"Examples of suitable antibacterial agents nonexclusively include bacitracin, erythromycin, neomycin, tetracycline, chlortetracycline, benzethonium chloride, phenol, and mixtures thereof.\",\n \"Examples of suitable skin emollients and skin moisturizers nonexclusively include mineral oil, lanolin, vegetable oils, isostearyl isostearate, glyceryl laurate, methyl gluceth-10, methyl gluceth-20 chitosan, and mixtures thereof.\",\n \"Examples of sunscreen agents nonexclusively include benzophenones, bornelone, butyl paba, cinnamidopropyl trimethyl ammonium chloride, disodium distyrylbiphenyl disulfonate, paba, potassium methoxycinnamate, butyl methoxydibenzoylmethane, octyl methoxycinnamate, oxybenzone, octocrylene, octyl salicylate, phenylbenzimidazole sulfonic acid, ethyl hydroxypropyl aminobenzoate, menthyl anthranilate, aminobenzoic acid, cinoxate, diethanolamine methoxycinnamate, glyceryl aminobenzoate, titanium dioxide, zinc oxide, oxybenzone, Padimate O, red petrolatum, and mixtures thereof.\",\n \"Further examples of sunscreen active agents include, but are not limited to octyl methoxycinnamate (ethylhexyl p-methoxycinnamate), octyl salicylate oxybenzone (benzophenone-3), benzophenone-4, menthyl anthranilate, dioxybenzone, aminobenzoic acid, amyl dimethyl PABA, diethanolamine p-methoxy cinnamate, ethyl 4-bis (hydroxypropyl) aminobenzoate, 2-ethylhexy 1-2-cyano-3,3-diphenylacrylate, homomenthyl salicylate, glyceryl aminobenzoate, dihydroxyacetone, octyl dimethyl PABA, 2-phenylbenzimidazole-5-sulfonic acid, triethanolamine salicylate, zinc oxide, and titanium oxide, and mixtures thereof.\",\n \"Examples of suitable anti-aging agents include, but are not limited to inorganic sunscreens such as titanium dioxide and zinc oxide; organic sunscreens such as octyl-methoxy cinnamates and derivatives thereof; retinoids; vitamins such as vitamin E, vitamin A, vitamin C, vitamin B, and derivatives thereof such as vitamin E acetate, vitamin C palmitate, and the like; antioxidants including beta carotene, alpha hydroxy acids such as glycolic acid, citric acid, lactic acid, malic acid, mandelic acid, ascorbic acid, alpha-hydroxybutyric acid, alpha-hydroxyisobutyric acid, alpha-hydroxyisocaproic acid, atrrolactic acid, alpha-hydroxyisovaleric acid, ethyl pyruvate, galacturonic acid, glucoheptonic acid, glucoheptono 1,4-lactone, gluconic acid, gluconolactone, glucuronic acid, glucuronolactone, glycolic acid, isopropyl pyruvate, methyl pyruvate, mucic acid, pyruvic acid, saccharic acid, saccaric acid 1,4-lactone, tartaric acid, and tartronic acid; beta hydroxy acids such as beta-hydroxybutyric acid, beta-phenyl-lactic acid, beta-phenylpyruvic acid; botanical extracts such as green tea, soy, milk thistle, algae, aloe, angelica, bitter orange, coffee, goldthread, grapefruit, hoellen, honeysuckle, Job's tears, lithospermum, mulberry, peony, puerarua, nice, safflower, and mixtures thereof.\",\n \"Examples of suitable external analgesics and local anesthetics nonexclusively include benzocaine, dibucaine, benzyl alcohol, camphor, capsaicin, capsicum, capsicum oleoresin, juniper tar, menthol, methyl nicotinate, methyl salicylate, phenol, resorcinol, turpentine oil, and mixtures thereof.\",\n \"Examples of suitable antiperspirants and deodorants nonexclusively include aluminium chlorohydrates, aluminium zirconium chlorohydrates, and mixtures thereof.\",\n \"Examples of suitable counterirritants nonexclusively include camphor, menthol, methyl salicylate, peppermint and clove oils, ichtammol, and mixtures thereof Examples of suitable inflammation inhibitors nonexclusively includes hydrocortisone, Fragaria Vesca, Matricaria Chamomilla, and Salvia Officinalis.\",\n \"Other well-known antipruritic agents include phenol, camphor, menthol, hydro-cortisone, hydrocortisone acetate, camphorated metacresol, phenolated sodium, and mixtures thereof.\",\n \"Other preferred benefit agents nonexclusively include DMAE, soy and derivatives thereof, colloidal oatmeal, sulfonated shale oil, olive leaf, elubiol, 6-(1-piperidinyl)-2,4-pyrimidinediamine-3-oxide, finasteride, ketoconazole, salicylic acid, zinc pyrithione, coal tar, benzoyl peroxide, selenium sulfide, hydrocortisone, sulfur, menthol, pramoxine hydrochloride, tricetylmonium chloride, polyquaternium 10, panthenol, panthenol triacetate, vitamin A and derivatives thereof, vitamin B and derivatives thereof, vitamin C and derivatives thereof, vitamin D and derivatives thereof, vitamin E and derivatives thereof, vitamin K and derivatives thereof, keratin, lysine, arginine, hydrolyzed wheat proteins, hydrolyzed silk proteins, octyl methoxycinnamate, oxybenzone, minoxidil, titanium dioxide, zinc dioxide, retinol, erthromycin, tretinoin, and mixtures thereof.\",\n \"One preferred type of benefit agent includes those therapeutic components that are effective in the treatment of seborrheic dermatitis and psoriasis as well as the symptoms associated therewith.\",\n \"Examples of such suitable benefits agents nonexclusively include zinc pyrithione, anthralin, shale oil and derivatives thereof such as sulfonated shale oil, selenium sulfide, sulfur; salicylic acid; coal tar; povidone-iodine, imidazoles such as ketoconazole, dichlorophenyl imidazolodioxalan, which is commercially available from Janssen Pharmaceutica, Nev., under the tradename, “Elubiol”, clotrimazole, itraconazole, miconazole, climbazole, tioconazole, sulconazole, butoconazole, fluconazole, miconazole nitrate and any possible stereo isomers and derivatives thereof; piroctone olamine (Octopirox); selenium sulfide; ciclopirox olamine; anti-psoriasis agents such as vitamin D analogs, e.g.\",\n \"calcipotriol, calcitriol, and tacaleitrol; vitamin A analogs such as esters of vitamin A, e.g.\",\n \"vitamin A palmitate, retinoids, retinols, and retinoic acid; corticosteroids such as hydrocortisone, clobetasone, butyrate, clobetasol propionate and mixtures thereof.\",\n \"Further examples of benefit agents are emollients, skin conditioning agents, humectants, preservatives, antioxidants, perfumes, chelating agents, or mixtures thereof.\",\n \"Emollients in the composition of the invention function have ability to remain on the skin surface or in the stratum corneum to act as lubricants, to reduce flaking, and to improve the skin appearance.\",\n \"Typical emollients include fatty esters, fatty alcohols, mineral oil, polyether siloxane copolymers and the like.\",\n \"Examples of suitable emollients include, but are not limited to, polypropylene glycol (“PPG”)-15 stearyl ether, PPG-10 acetyl ether, steareth-10, oleth-8, PPG-4 lauryl ether, vitamin E acetate, PEG-7 glyceryl cocoate, lanolin, cetyl alcohol, (e.g., Cetyl Alcohol NF available from Lotioncrafter LLC) octyl hydroxystearate, dimethicone (e.g., Xiameter® PMX-200 Silicone Fluid 100CS available from Dow Corning), and combinations thereof.\",\n \"Examples of skin conditioning agents include, but are not limited to, olive leaf, sulfonated shale oil, elubiol, 6-(1-piperidinyl)-2,4-pyrimidinediamine-3-oxide, finasteride, ketoconazole, zinc pyrithione, coal tar, benzoyl peroxide, selenium sulfide, hydrocortisone, pramoxine hydrochloride, tricetylammonium chloride, polyquaternium 10, panthenol, panthenol triacetate, vitamin B and derivatives thereof, vitamin C and derivatives thereof, vitamin D and derivatives thereof, vitamin E and derivatives thereof, vitamin K and derivatives thereof, keratin, lysine, arginine, hydrolyzed wheat proteins, hydrolyzed silk proteins, octyl methoxycinnamate, oxybenzone, minoxidil, titanium dioxide, zinc dioxide, erthromycin, tretinoin, and mixtures thereof.\",\n \"Polyhydric alcohols can be utilized as humectants in the compositions of the invention.\",\n \"The humectants aid in increasing the effectiveness of the emollient, reduce scaling, stimulate removal of built-up scale and improve skin feel.\",\n \"Suitable polyhydric alcohols include, but are not limited to, glycerol (also known as glycerin), polyalkylene glycols, alkylene polyols and their derivatives, including butylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, polyethylene glycol and derivatives thereof, sorbitol, hydroxypropyl sorbitol, hexylene glycol, 1,3-dibutylene glycol, 1,2,6,-hexanetriol, ethoxylated glycerol, propoxylated glycerol and mixtures thereof.\",\n \"Examples of suitable preservatives for use in the compositions of the invention include the Ci-C4 alkyl parabens and phenoxyethanol (e.g., Microcare® PE available from Thor Personal Care).\",\n \"Suitable antioxidants include butylated hydroxy toluene (BHT), ascorbyl palmitate, butylated hydroanisole (BHA), phenyl-[alpha]-naphthylamine, hydroquinone, propyl gallate, nordihydroquiaretic acid, vitamin E or derivatives of vitamin E, vitamin C and derivatives thereof, calcium pantothenic, green tea extracts and mixed polyphenols, and mixtures thereof.\",\n \"Any fragrance may be added to the compositions of the invention for aesthetic purposes.\",\n \"Suitable fragrances include, but are not limited to, eucalyptus oil, camphor synthetic, peppermint oil, clove oil, lavender, chamomile and the like.\",\n \"In certain aspects of this invention, the compositions may include a chelating agent.\",\n \"Chelating agents which are useful in the compositions of present invention include ethylenediamine tetra acetic acid (EDTA) and derivatives and salts thereof, dihydroxyethyl glycine, tartaric acid, and mixtures thereof.\",\n \"It is also envisioned that the composition of this invention could be combined with other agents topical anesthetics, for example, such as benzocaine or other caine type molecules, or even mild steroids such as hydrocortisone for enhanced anti-inflammatory activity.\",\n \"Further benefit agents useful in the compositions and methods of the present invention include, but are not limited to: antihistamine/antipruritic drugs, such as ethanolamines (e.g., diphenhydramine, diphenhydramine hydrochloride, clemastine, clemastine fumarate, and the like), ethylenediamines (e.g., brompheniramine, brompheniramine maleate, chlorpheniramine, chlorpheniramine maleate, dexchlorpheniramine maleate, triprolidine, triprolidine hydrochloride, and the like), phenothiazines (e.g., promethazine), piperidines (e.g., hydroxzine, hydroxyzine hydrochloride, terfenadine, astemizole, azatadine, azatadine maleate, and the like), cyproheptadine, cyproheptadine hydrochloride, loratidine, carbinoxamine maleate, diphenylpyraline hydrochloride, phenindamine tartrate, tripelennamine hydrochloride, methdilazine hydrochloride, trimprazine tartrate, and the like; immunosuppressants, such as glucocorticoids (methylprednisolone), myelin basic protein (e.g., 7-capaxone), anti-Fe receptor monoclonal antibodies, hydroorotate dehydrogenase inhibitor, anti-IL2 monoclonal antibodies (e.g., CHI-621 and dacliximab), buspirone, castanospermine, CD-59 (complement factor inhibitor), 5-lipoxygenase inhibitor (e.g., CMI-392), phosphatidic acid synthesis antagonists, ebselen, edelfosine, enlimomab, galaptin, platelet activating factor antagonists, selectin antagonists (e.g., ICAM-4), interleukin-10 agonist, macrocylic lactone, methoxatone, mizoribine, OX-19, peptigen agents, PG-27, protein kinase C inhibitors, phosphodiesterase IV inhibitor, single chain antigen binding proteins, complement factor inhibitor, sialophorin, sirolimus, spirocyclic lactams, 5-hydroxytryptamine antagonist, anti-TCR monoclonal antibodies, CD5 gelonin and TOK-8801, and the like; antibacterial agents (e.g., amikacin sulfate, aztreonam, chloramphenicol, chloramphenicol palmitate, chloramphenicol sodium succinate, ciprofloxacin hydrochloride, clindamycin hydrochloride, clindamycin palmitate, clindamycin phosphate, metronidazole, metronidazole hydrochloride, gentamicin sulfate, lincomycin hydrochloride, tobramycin sulfate, vancomycin hydrochloride, polymyxin B sulfate, colistimethate sodium, colistin sulfate, and the like); antifungal agents (e.g., griseofulvin, keloconazole, and the like); antiviral agents (e.g., interferon gamma, zidovudine, amantadine hydrochloride, ribavirin, acyclovir, and the like); antimicrobials (e.g., cephalosporins (e.g., cefazolin sodium, cephradine, cefaclor, cephapirin sodium, ceftizoxime sodium, cefoperazone sodium, cefotetan disodium, cefutoxime azotil, cefotaxime sodium, cefadroxil monohydrate, ceftazidime, cephalexin, cephalothin sodium, cephalexin hydrochloride monohydrate, cefamandole nafate, cefoxitin sodium, cefonicid sodium, ceforanide, ceftriaxone sodium, ceftazidime, cefadroxil, cephradine, cefuroxime sodium, and the like), penicillins (e.g., ampicillin, amoxicillin, penicillin G benzathine, cyclacillin, ampicillin sodium, penicillin G potassium, penicillin V potassium, piperacillin sodium, oxacillin sodium, bacampicillin hydrochloride, cloxacillin sodium, ticarcillin disodium, azlocillin sodium, carbenicillin indanyl sodium, penicillin G potassium, penicillin G procaine, methicillin sodium, nafcillin sodium, and the like), erythromycins (e.g., erythromycin ethylsuccinate, erythromycin, erythromycin estolate, erythromycin lactobionate, erythromycin siearate, erythromycin ethylsuccinate, and the like), tetracyclines (e.g., tetracycline hydrochloride, doxycycline hyclate, minocycline hydrochloride, and the like), and the like); antioxidants (e.g., N-acetylcsysteine, Vitamin A, Vitamin C, Vitamin E, .beta.-carotene, EUK-8, flavonoids, glutathione, .alpha.lipoic acid, melatonin, retinols, and the like); anti-infectives (e.g., miconazole, vidarabine, inosine, pranobex, vidarabine, inosine prabonex, cefpimizole sodium), fradiomycin, and the like); hormones (e.g., androgens (e.g., danazol, testosterone cypionate, fluoxymesterone, ethyltostosterone, testosterone enanihate, methyltestosterone, fluoxymesterone, testosterone cypionate), estrogens (e.g., estradiol, estropipate, conjugated estrogens), progestins (e.g., methoxyprogesterone acetate, norethindrone acetate), corticosteroids (e.g., triamcinolone, betamethasone, betamethasone sodium phosphate, dexamethasone, dexamethasone sodium phosphate, dexamethasone acetate, prednisone, methylprednisolone acetate suspension, triamcinolone acetonide, methylprednisolone, prednisolone sodium phosphate methylprednisolone sodium succinate, hydrocortisone sodium succinate, methylprednisolone sodium succinate, triamcinolone hexacatonide, hydrocortisone, hydrocortisone cypionate, prednisolone, fluorocortisone acetate, paramethasone acetate, prednisolone tebulate, prednisolone acetate, prednisolone sodium phosphate, hydrocortisone sodium succinate, and the like), thyroid hormones (e.g., levothyroxine sodium) and the like), and the like; psoriasis agents, such as 5-LO inhibitors (e.g., Wy-50295, Wy-49232, Lonapalene, RS-43179, MK-886, L-663536, ETH-615, DUP-654, Zileuton, epocarbazolin-A, and A-64077), 5-LO/CO inhibitors (e.g., BF-397, Tenidap, CP-309, and CP-66248), angiogenesis inhibitors (e.g., platelet factor 4), anticancer antibiotic (e.g., AGM-1470, and TNP-470), anti-inflammatory cytochrome P450 oxidoreductase inhibitors (e.g., DuP-630, and DuP-983), antiproliferative compounds (e.g., Zyn-Linker), arachidonic acid analogues (e.g., CD581, and CD554), arachidonic acid antagonists (e.g., Lonopalene, RS-43179, triamcinolone acetonide with penetration enhancer Azone, betamethasone dipropionate steroid wipe, G-202, Halobetasol propionate, ultravate, Halometasone, C-48401-Ba, and Sicorten), beta-glucan receptor antagonists, betamethasone steroid wipes, calcium metabolic moderators (e.g., Tacalcitol, Bonealfa, TV-02 ointment, Ro-23-6474, KH-1060, Calcipotriol, BMS-181161, BMY-30434, Dovonex, and Divonex), CD4 binding inhibitors (e.g., PIC 060), cell adhesion compounds (e.g., CY-726, VCAM-1, ELAM-1, and ICAM), cell adhesion inhibitors (e.g., selectin inhibitor, GM-1930), cellular aging inhibitors (e.g., Factor X), corticosteroids (e.g., Halobetasol propionate, ultravate, Halometasone, C-48401-Ba, and Sicorten), cyclosporin analogues (e.g., IMM-125), dihydrofolate reductase inhibitors (e.g., G-301, dichlorobenzoprim, methotrexate, and methotrexate in microsponge delivery system), E-selectin inhibitors (e.g., ISIS 4730), endogenous active form of vitamin D3 (e.g., Calcitriol, and Du-026325), fibroblast growth factor antagonists (e.g., Saporin mitotoxin, and Steno-Stat), fumagillin analogues (e.g., AGM-1470, and TNP-470), G-proteins and signal transduction compounds (e.g., CPC-A), gel formulations for acne (e.g., nicotinamide, N-547, and Papulex), growth hormone antagonists (e.g., Octreotide, Sandostatin, Lanreotide, angiopeptin, BIM-23014, and Somatuline), humanized antibodies (e.g., anti-CD4 antibody), hydroorotate dehydrogenase inhibitors (e.g., Brequinar sodium, bipenquinate, and DuP-785), ICAM-1 inhibitors (e.g., ISIS 939), IL-1 and other cytokine inhibitors (e.g., Septanil), IL-1 converting ezyme inhibitors, IL-1 receptor antagonists (e.g., Antril), IL-2 antagonists (e.g., Tacrolimus, Prograf, and FK-506), IL-2 receptor-targeted fusion toxins (DAB389IL-2), IL-8 receptors, immunostimulants (e.g., Thymopentin, and Timunox), immunosuppressants (e.g., XomaZyme-CD5 Plus, cyclosporine, Sandimmune, SR-31747, anti-CD 11, 18 MAb, Tacrolimus, Prograf, FK-506, and FK-507), immunosuppressive agents targeting FK506 (e.g., immunophilins, VX-10367, and VX-10428), immunotoxins MAb directed against CD antigen (e.g., XomaZyme-CD5 Plus), leukotriene antagonists (e.g., Sch-40120, Wy-50295, and Wy49232), leukotriene B4 antagonists (e.g., SC-41930, SC-50605, SC-48928, ONO-4057, LB-457, LY-255283, LY-177455, LY-223982, LY-223980, and LY-255253), leukotriene synthesis inhibitors (MK-886, and L-663536), lipase clearing factor inhibitors (e.g., 1-docosanol, and lidakol), lipid encapsulated reducing agent (e.g., Dithranol), liposomal gel (e.g., Dithranol), LO inhibitors (e.g., CD581, CD554, Masoprocol, and Actinex), lithium succinate ointments (e.g., lithium salts, and Efalith), LO/CO inhibitors (e.g., P-8892, P-8977, CHX-108, and FPL-62064), membrane integrity agonists (e.g., lithium salts, and Efalith), microtubule inhibitors (e.g., Posophyliotoxin-containing compound, and Psorex), octapeptide somatostatin analogues (e.g., Lanreotide, angiopeptin, BIM-23014, and Somatuline), oligonucleotides (e.g., ISIS 4730, ISIS 3801, ISIS 1939, and IL-1 inhibitors), peptide agonists (e.g., octapeptide, and peptide T), PKC inhibitors, phospholipase A2 compounds, pospholipase D compounds, photodynamic anticancer agents (e.g., 5-aminolevulinic acid, and 5-ALA), photodynamic therapies (e.g., benzoporphyrin derivative, synthetic chlorins, synthetic porphyrins, and EF-9), photosensitizer (e.g., Porfirmer sodium), PKC inhibitors (e.g., Safingol, and Kynac), platelet activating factor antagonists (e.g., TCV-309), platelet aggregation inhibitors (e.g., CPC-A), prodrug NSAIDs (e.g., G-201), prostaglandin agonist (e.g., eicosapentaenoic acid +gamma-linolenic acid combination, and Efamol Marine), protein inhibitors (e.g., SPC-103600, and SPC-101210), protein kinase C (PKC) inhibitors (e.g., Ro-31-7549, Ro-31-8161, and Ro-31-8220), protein synthesis antagonists (e.g., Calcitriol, Du-026325, LG-1069, LG-1064, AGN-190168, Namirotene, and CBS-211A), purine nucleoside phosphorylase inhibitors (e.g., BCX-34), radical formation agonists (e.g., benzoporphyrin derivative), recombinant antileukoproteinases (e.g., ALP-242), retinoids (e.g., BMY-30123, LG-1Q69, and LG-1064), retinoid derivatives (e.g., AGN-190168), rapamycin binding proteins (FKBP) (e.g., immunophilins, VX-10367, and VX-10428), second generation monoaromatic retinoids (e.g., Acitretin, and Neotigason), soluble IL-1, IL-4 and IL-7 receptors, somatostatin and somatostatin analogues (e.g., Octreotide, and Sandostatin), steroids, (e.g., AGN-191743), streptomyces anulatus isolates (e.g., epocarbazolin-A), superoxide dismutase (e.g., EC-SOD-B), thymidylate synthase inhibitors (e.g., AG-85, MPI-5002, 5-FU in biodegradable gel-like matrix, 5-FU and epinephrine in biodegradable gel-like matrix, and AccuSite), topical formulations (e.g., P-0751, and P-0802), transglutaminase inhibitors, tyrphostin EGF receptor kinase blockers (e.g., AG-18, and AG-555), VCAM-1 inhibitors (e.g., ISIS 3801), vitamin D analogues (e.g., Ro-23-6474, KH-1060, Calcipotriol, BMS-181161, BMY-30434, Dovonex, and Divonex), vitamin D3 analogues (e.g., Tacalcitol, 20 Bonealfa, TV-02 ointment), and vitamin D3 derivatives (e.g., 1,2-diOH-vitamin D3), and the like; and agents useful for the treatment of carcinomas (e.g., adriamycin, taxol, interleukin-1, interleukin-2 (especially useful for treatment of renal carcinoma), and the like, as well as leuprolide acetate, LHRH analogs (such as nafarelin acetate), and the like, which are especially useful for the treatment of prostatic carcinoma).\",\n \"The amount of benefit agent to be included may vary depending upon, for example, the ability of the benefit agent to penetrate through the skin, the specific benefit agent chosen, the particular benefit desired, the sensitivity of the user to the benefit agent, the health condition, age, and skin condition of the user, and the like.\",\n \"In sum, the benefit agent is used in a “safe and effective amount,” which is an amount that is high enough to deliver a desired skin benefit or to modify a certain condition to be treated, but is low enough to avoid serious side effects, at a reasonable risk to benefit ratio within the scope of sound medical judgment.\",\n \"Formulations The compositions of the present invention can be prepared and administered in a wide variety of topical forms.\",\n \"For topical formulations of the present invention, dermatologically acceptable carriers can be either solid or liquid.\",\n \"The compositions of this invention is preferably in the form of topical products that can be applied externally to the skin and can be prepared in accordance with conventional techniques known to those of ordinary skill in the art.\",\n \"The carrier may take a variety of physical forms such as, for example, creams, dressings, gels, lotions, ointments or liquids.\",\n \"One could also utilize this in a convenient spray applicator.\",\n \"Typical carriers include lotions containing water and/or alcohols and emollients such as hydrocarbon oils and waxes, silicone oils, hyaluronic acid, vegetable, animal or marine fats or oils, glyceride derivatives, fatty acids or fatty acid esters or alcohols or alcohol ethers, lanolin and derivatives, polyhydric alcohols or esters, wax esters, sterols, phospholipids and the like, and generally also emulsifiers (nonionic, cationic or anionic), although some of the emollients inherently possess emulsifying properties.\",\n \"These same general ingredients can be formulated into a cream rather than a lotion, or into gels, or into solid sticks by utilization of different proportions of the ingredients and/or by inclusion of thickening agents such as gums or other forms of hydrophillic colloids.\",\n \"The compositions according to the invention preferably contain an effective stabilizing amount of an emulsifier.\",\n \"Any emulsifier that is compatible with the components of the composition can be employed.\",\n \"Suitable emulsifiers include stearic acid, acetyl alcohol, stearyl alcohol, steareth 2, steareth 20, Acrylates/C10-30 alkyl Acrylate Crosspolymer Particularly preferred is PEMULEN TR-1 (CTFA Designation: Acrylates/10-30 Alkyl Acrylate Crosspolymer).\",\n \"The composition of the invention may be in the form of an oil-in-water emulsion, a water-in-oil emulsion, or a dispersion.\",\n \"Liquid form preparations such as lotions or creams include solutions, suspensions, and emulsions, for example, water or DMSO/propylene glycol solutions.\",\n \"Liquid suspensions suitable for topical use can be made by dispersing the finely divided active component in an appropriate liquid with viscous material, such as natural or synthetic gums, resins, methycellulose, sodium carboxymethylcellulose, and other well-known suspending agents.\",\n \"Also included are solid form preparations which are intended to be converted, shortly before use, to liquid form preparations for topical administration.\",\n \"Such liquid forms include solutions, suspensions, and emulsions.\",\n \"These preparations may contain, addition to the active component, colorants, flavors, fragrances, stabilizers, buffers, artificial and natural sweeteners, dispersants, thickeners, solubilizing agents, and the like.\",\n \"To prepare dermally applicable formulations it is possible to use the previously mentioned substances and spreadable or liquid hydrocarbons such as Vaseline or paraffin or gels of alkanes and polyethylene, fats and oils of plant or animal origin, which may in part also be hydrated, or synthetic fats such as glycerides of fatty acids C8 -C18, as well as beeswax, cetyl palmitate (e.g., Cutina® CP available from Cognis/BASF), wool wax, wool wax alcohols, fatty alcohols such as cetyl alcohol, stearyl alcohol, polyethylene glycols of molecular weight 200 to 20,000; liquid waxes such as isopropyl myristate, isopropyl stearate, ethyloleate; emulsifiers such as sodium, potassium, ammonium salts of stearic acid or palmitic acid as well as triethalolamine stearate, alkali salts of oleic acid, castor oil acid, salts of sulfurated fatty alcohols such as sodium lauryl sulphate, sodium cetyl sulphate, sodium stearyl sulphate, salts of gallic acid, sterols such as cholesterol, partial fatty acid esters of multivalent alcohols such as ethylene glycol monostearate, glycerol monostearate, pentaerythritol monostearate, partial fatty acid esters of sorbitan, partial fatty acid esters of polyoxyethylene sorbitan, sorbitol ethers of polyoxyethylene, fatty acid esters of polyoxyethylene, fatty alcohol ethers of polyoxyethylene, fatty acid esters of saccharose, fatty acid esters of polyglycerol, lecithin.\",\n \"Examples of suitable esters nonexclusively include a branched C5 to C22 alkyl alcohol ester of an aromatic acid, a straight-chained or branched C5 to C22 alkyl acid esters of optionally ethyoxylated/propoxylated polyols having from about 3 carbon atoms to about 7 carbon atoms, a branched C5 to C22 alkyl alcohol esters of branched polyacids, a branched or straight-chained Cs to C22 alkyl acid esters of branched and/or unsaturated C5 to C22 alkyl alcohols, a branched or unsaturated C5 to C22 alkyl alcohol esters of an acid selected from the group consisting of adipic acid, succinic acid, maleic acid, sebacic acid, and mixtures thereof, polyether interrupted fatty acid esters, benzoic acid ester of heterogeneous alcohols having from about 8 carbon atoms to about 22 carbon atoms and mixtures thereof with straight-chained or branched C5 to C22 alkyl acid esters of optionally ethyoxylated/propoxylated polyols, benzoic acid esters of heterogeneous alcohols, and mixtures thereof.\",\n \"Further suitable esters are disclosed in U.S. Pat.\",\n \"No.\",\n \"6,762,158, the entire disclosure of which is incorporated herein by reference.\",\n \"Antioxidants that may for example be used are sodium metabisulphite, ascorbic acid, gallic acid, gallic acid alkyl ester, butylhydroxyanisol, nordihydroguaiacic acid, tocopherols as well as tocopherols .+-.synergitic substances that bind heavy metals through complex formation, for example lecithin, ascorbic acid, phosphoric acid).\",\n \"Conserving agents that may for example be considered are sorbic acid, p-hydroxybenzoic acid esters (for example lower alkyl esters), benzoic acid, sodium benzoate, trichloroisobutyl alcohol, phenol, cresol, benzethonium chloride and formalin derivatives.\",\n \"Topical dosage forms include, but are not limited to, sprays, aerosols, creams, lotions, ointments, gels, solutions, emulsions, suspensions, or other forms known to one of skill in the art.\",\n \"See, e.g., Remington's Pharmaceutical Sciences, 16th and 18th eds., Mack Publishing, Easton Pa. (1980 & 1990); and Introduction to Pharmaceutical Dosage Forms, 4th ed., Lea & Febiger, Philadelphia (1985).\",\n \"See also Cosmetic Model Formulae—A Compilation of Model Formulae for the Manufacture of Cosmetic Preparations (Henkel KGaA; 1988), the entirety of which is incorporated herein by reference.\",\n \"Transdermal dosage forms include “reservoir type” or “matrix type” patches, which can be applied to the skin and worn for a specific period of time to permit the penetration of a desired amount of active ingredients.\",\n \"Suitable excipients (e.g., carriers and diluents) and other materials that can be used to provide transdermal, topical, and mucosal dosage forms are well known to those skilled in the pharmaceutical arts, and depend on the particular tissue to which a given pharmaceutical composition or dosage form will be applied.\",\n \"The pH of the inventive compositions may also be adjusted to improve delivery of one or more active ingredients.\",\n \"In another preferred embodiment, the compositions used in the methods of present invention contain a pH-buffering agent.\",\n \"Preferably, the amount of buffering agent should be that which would result in compositions having a pH ranging from about 4.5 to about 8:5, more preferably from about 5.5 to about 8.5, most preferably from about 6.5 to about 8.0.The buffering agent can be any of the known buffering agents commonly found in topical compositions provided that they are physically and chemically stable with the other ingredients of the composition.\",\n \"Suitable buffering agents include organic acids such as, but not intended to be restricted to, citric acid, malic acid, and glycolic acid.\",\n \"Similarly, the polarity of a solvent carrier, its ionic strength, or tonicity can be adjusted to improve delivery.\",\n \"Compounds such as stearates may also be added to pharmaceutical compositions or dosage forms to advantageously alter the hydrophilicity or lipophilicity of one or more active ingredients so as to improve delivery.\",\n \"In this regard, stearates can serve as a lipid vehicle for the formulation, as an emulsifying agent or surfactant, and as a delivery-enhancing or penetration-enhancing agent.\",\n \"Different salts, hydrates or solvates of the active ingredients can be used to further adjust the properties of the resulting composition.\",\n \"The topical compositions of the present invention may contain a water dispersible component, which is preferably a water soluble solvent.\",\n \"As used herein, the term “water dispersible component” shall mean a material that produces a uniform, clear or hazy, mixture when combined with at least a weight equivalent of water.\",\n \"Examples of suitable water dispersible components nonexclusively include polyethylene glycol 400, hexylene glycol, propylene glycol, polypropylene glycol-10 methylglucose ether, ethoxydiglycol, polyethylene glycol-6 caprylic/capric glyceride, ethylene glycol monobutyl ether, polyethylene glycol-8 caprylic/capric glycerides, 3-methoxy-3-methyl-1-butanol, dimethyl isosorbide, and mixtures thereof.\",\n \"Most preferred water dispersible components include hexylene glycol, dimethyl isosorbide, polyethylene glycol-6 caprylic/capric glyceride, and mixtures thereof.\",\n \"A further optional component of the compositions of the present invention is a volatile or nonvolatile liquid silicone.\",\n \"Examples of suitable silicones nonexclusively include the polydimethyl siloxanes and derivatives thereof such as hexamethylsiloxane, dimethicone, dimethiconol, and cyclomethicone, with cyclomethicone being preferred.\",\n \"Examples of suitable cyclomethicones nonexclusively include cyclotetradimethyl siloxane; cyclopentadimethyl siloxane, cyclohexadimethyl siloxane, cycloheptadimethyl siloxane, and mixtures thereof.\",\n \"Further optional components of the compositions of the present invention are polymeric emulsifiers and/or thickeners.\",\n \"Examples of suitable polymeric emulsifiers nonexclusively include polyethylene glycol-30 dipolyhydroxystearate, dimethicone copolyol, substituted acrylates, and mixtures thereof Examples of suitable hydrophilic thickeners nonexclusively include carbomers (e.g., Carbopol® Ultrez polymers available from Lubrizol Corp.; also various carbomer prodcts available from B. F. Goodrich), acrylate copolymers, hydroxyethylcellulose modified with cetyl ether groups, polyvinylmethyl ether/maleic anhydride (PVM/MA) decadiene crosspolymer, and copolymers and mixtures thereof.\",\n \"Examples of suitable acrylate copolymers nonexclusively include acrylate copolymers available from Rohm & Haas, acrylates/aminoacrylates copolymer, acrylates/steareth-20 itaconate copolymer, acrylates/ceteth-20 itaconate copolymer, acrylates/steareth-20 methacrylate copolymer, and copolymers and mixtures thereof.\",\n \"The compositions of the present invention may also optionally contain a stability enhancer for the purpose of enhancing the stability of the benefit agent and/or the aesthetics of the composition.\",\n \"Generally, the stability enhancer may be selected from a nonionic emulsifier, an essentially non-foaming surfactant, or mixtures thereof.\",\n \"Examples of suitable nonionic emulsifiers include isocetheth-20, oleth-2, mixture of PEG-40 hydrogenated castor oil and trideceth-9, Poloxamer 184, laureth-4, sorbitan trioleate, polyoxyethylene-(2) oleyl ether, sorbitan stearate, cetearyl glucoside, glyceryl oleate, trideceth-9, polyethylene glycol-40 hydrogenated castor oil, and mixtures thereof.\",\n \"Examples of suitable essentially non-foaming surfactants include non-foaming nonionic surfactants such as sucrose esters, e.g., sucrose cocoate, sucrose stearate and mixtures thereof.\",\n \"By “essentially non-foaming,” it is meant that the surfactant, when used with the composition of the present invention, has a column height of less than about 20 mm as determined by the Ross-Miles Foam Generation Test.\",\n \"See 18 (I.)\",\n \"Oil & Soap 99-102 (1941)(“Ross-Miles Test”), which is incorporated by reference herein.\",\n \"The composition may either be rinseable with water or may be wiped-off.\",\n \"Preferably, the essentially non-foaming surfactants are used in embodiments wherein the composition is rinseable with water.\",\n \"The composition may also optionally contain a foaming surfactant.\",\n \"The foaming surfactant may be non-ionic, cationic, amphoteric, or anionic.\",\n \"By “foaming,” it is meant that the surfactant, when used with the composition of the present invention, has a column height of foam greater than about 20 mm as determined by the Ross-Miles Test.\",\n \"Preservatives for the formulations herein are benzoic acid and derivatives thereof, namely, butylparaben, ethylparaben, methylparaben, propylparaben, sodium benzoate, and mixtures thereof.\",\n \"Typical use of benzoic-acid-derived preservative is a mixture of methylparaben comprising up to 0.3 percent by weight of the treating composition and propylparaben comprising up to 0.1 percent by weight of the treating composition.\",\n \"Other useful preservatives include alcohol, benzalkonium chloride, benzethonium chloride, benzyl alcohol, bronopol, cetrimide, chlorhexidine, chlorobutanol, chlorocresol, cresol, glycerin, imidurea, phenol, phenoxyethanol, phenylethyl alcohol, phenylmercuric acetate, phenylmercuric borate, phenylmercuric nitrate, potassium sorbate, propylene glycol, sodium propionate, sorbic acid and thimerosal.\",\n \"Among the inactive ingredients are surfactants and emulsifying agents.\",\n \"These ingredients take on importance as the use thereof improves absorption, coverage, appearance, and feel of the product.\",\n \"Some suitable emulsifying agents are acacia, anionic emulsifying wax, carbomer, carboxymethyl cellulose, cetostearyl alcohol, cetyl alcohol, cholesterol, diethanolamine, glyceryl monostearate, hydrous lanolin, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, lanolin, lanolin alcohols, lecithin, methylcellulose, mineral oil and lanolin alcohols, monobasic sodium phosphate, monoethanolamine, nonionic emulsifying wax, oleic acid, poloxamer, polyoxyethylene alkyl ethers, polyoxyethylene castor oil derivatives, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates, propylene glycol alginate, sodium lauryl sulfate, sorbitan esters, stearic acid, triethanolamine, and xanthan gum.\",\n \"Frequently mixtures of complimentary surfactants are used in a given formulation.\",\n \"Suitable anionic surfactants are lauryl sulfates, including sodium lauryl sulfate, triethanolamine lauryl sulfate, and ammonium lauryl sulfate; laureth sulfates,including sodium laureth sulfate, triethanolamine laureth sulfate, and ammonium laureth sulfate; sarcosines, including lauryl sarcosine, and sodium lauryl sarcosinate; sulfosuccinates, including disodium oleamine sulfosuccinate, and sodium dioctyl sulfosuccinate; and docusate sodium.\",\n \"The cationic surfactants are benzalkonium chloride, benzethonium chloride, and cetrimide.\",\n \"The nonionic surfactants are glyceryl monooleate, polyvinyl alcohol, sorbitan esters, povidone, crospovidone, polyoxyethylene fatty alcohols, polyoxyethylene sorbitol esters, and alkanolamides.\",\n \"Additionally, amphoteric detergents such as betaines, sultaines, and imidazolinium derivatives are used, and particularly ingredients such as cocamidopropyl betaine and sodium lauraminopropionate.\",\n \"In ointment and cream preparations, emollients form a vehicle to carry the active ingredients to the site of the immune response and the associated dermatitis.\",\n \"The emollient group from which these carriers are selected include allantoin, cetostearyl alcohol, cetyl esters wax, cocoa butter, cholesterol, dimethicone, glycerin, glyceryl monostearate, isopropyl myristate, isopropyl palmitate, kaolin, lecithin, light mineral oil, mineral oil, mineral oil and lanolin alcohols, petrolatum, and petrolatum and lanolin alcohols.\",\n \"The carrier can be any suitable aqueous dispersion material, cream, lotion, or ointment, which may include, for example hydrocolloids, plasdone, methyl cellulose, hydroxypropyl cellulose, lanolin, mineral oil, petroleum jelly, polyalkylene glycols such as polyethylene glycols, or mixtures thereof.\",\n \"The formulations may contain surfactants, antioxidants, and stabilizers such as benzoic acid, sorbic acid, parabens, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), vitamin E, sarcosonates, and the like.\",\n \"The benefit agents can also be combined with astringents such as witch hazel, aluminum acetate, aluminum sulfate, zinc oxide, zinc acetate, sodium bicarbonate, and calamine.\",\n \"One of the functions of the formulations when applied to contact dermatitis is to remove the irritant material from the skin.\",\n \"This requires astringent activity, and the addition of aluminum acetate, zinc oxide, zinc acetate, sodium bicarbonate, calamine, witch hazel, zinc carbonate, and aluminum hydroxide may be employed to enhance this physical property.\",\n \"A preferred carrier material includes water, glycerin, cetyl palmitate, mineral oil, caprylic/capric triglyceride, octyldodecanol, cetyl alcohol, glyceryl stearate, colloidal oat flour, dimethicone, PEG-40 stearate, carbomer, sodium hydroxide, phenoxy ethanol, caramel III coloring, DMDM hydantoin, and iodopropynyl butylcarbamate.\",\n \"Glycerin, also called glycerol, acts as a humectant, skin protectant, and solvent present in all natural lipids (fats), whether animal or vegetable.\",\n \"Whether natural or synthetic, glycerin is a humectant and extremely hygroscopic, meaning it readily absorbs water from other sources, attracting water from the environment and from the lower layers of skin (dermis) and increasing the amount of water in the surface layers of skin.\",\n \"Another aspect of glycerin's benefit is that it is a skin-identical ingredient, meaning it is a substance found naturally in skin.\",\n \"In that respect it is one of the many substances in skin that help maintain the outer barrier and prevent dryness or scaling.\",\n \"The Food and Drug Administration (FDA) includes glycerin on its list of direct food additives considered Generally Recognized As Safe (GRAS), and on its list of approved indirect food additives.\",\n \"Glycerin is also an FDA-approved active ingredient in Over-the-Counter (OTC) skin protectant drug products and ear drying products, and it is an approved demulcent for the eyes.\",\n \"Cetyl palmitate acts as an emollient, acting as a lubricant on the skin's surface, which gives the skin a soft and smooth appearance.\",\n \"The palmitates generally are esters of palmitic acid and ethylhexyl, cetyl, or isopropyl alcohol.\",\n \"In cosmetics and personal care products, they all function as skin conditioning agents and emollients.\",\n \"The palmitates are efficient opacifiers in cream and lotion shampoos.\",\n \"Isopropyl Palmitate also functions as a binder.\",\n \"The safety of the palmitates has been assessed by the Cosmetic Ingredient Review (CIR) Expert Panel.\",\n \"The CIR Expert Panel evaluated the scientific data and concluded that Ethylhexyl Palmitate, Cetyl Palmitate and Isopropyl Palmitate were safe as cosmetic ingredients.\",\n \"In 2001, the CIR Expert Panel considered available new data on Ethylhexyl, Cetyl and Isopropyl Palmitate and reaffirmed the above conclusion.\",\n \"Light mineral oil acts as an emollient, skin protectant, and solvent.\",\n \"Mineral oil functions as an emollient skin conditioning agent , an occlusive skin protectant, and as a solvent.\",\n \"The FDA permits the use of mineral oil as an active ingredient in the following OTC drug product categories: anorectal drugs, skin protectants, and ophthalmic emollients.\",\n \"Caprylic/capric triglyceride (CAS No.\",\n \"124-07-2) acts as a moisturizer, viscosity modulator, inactive carrier, and stabilizer.\",\n \"Caprylic/capric triglyceride is an oily liquid made from coconut oil.\",\n \"It is used in cosmetics and other personal care products, such as face creams, lipstick, eye makeup and foundations.\",\n \"It can also be used in perfumes, moisturizers and sunscreens.\",\n \"It is found naturally in foods but can also be made by industrial processes.\",\n \"Caprylic/capric triglyceride has a number of useful properties in the formulation of cosmetics and, in particular, face creams.\",\n \"Caprylic/capric triglyceride creates a barrier on the skin's surface, decreasing the amount of moisture lost through the skin, functioning not only to prevent dryness in skin, but also as a skin conditioning agent.\",\n \"It provides a slippery feeling and promotes dispersion of pigments in various colored cosmetics.\",\n \"Caprylic/capric triglycerides have a low viscosity.\",\n \"This property allows it to alter the thickness of a particular cosmetic product.\",\n \"Adding caprylic/capric triglycerides to thick face creams helps thin them out to the desired thickness.\",\n \"Caprylic/capric trigylceride does not readily oxidize.\",\n \"It is particularly useful as a stabilizer of emulsions.\",\n \"This property is particularly useful in facial creams and other cosmetic products, helping to give them a longer shelf life.\",\n \"The Food and Drug Administration lists caprylic/capric triglyceride as Generally Recognized As Safe, or GRAS, for use as a direct food additive.\",\n \"In addition, caprylic/capric triglyceride has been assessed by the Cosmetic Ingredient Review Expert Panel, which evaluated the scientific data and concluded, and reaffirmed in 2001, that it was safe as it was being used at that time.\",\n \"Similarly suitable triglyceride materials include medium-chain triglyceride oil (CAS 65381-09-1) available as MCT oil from Acme-Hardesty Oleochemicals.\",\n \"Octyldodecanol (CAS No.\",\n \"5333-42-6; Tegosoft® G20 available from Evonik) acts as a stabilizer, emulsifier, lubricant, and solvent.\",\n \"Octyldodecanol helps to form emulsions and prevent an emulsion from separating into its oil and liquid components.\",\n \"These ingredients also reduce the tendency of finished products to generate foam when shaken.\",\n \"When used in the formulation of skin care products, octyldodecanol acts as a lubricant on the skin surface, which gives the skin a soft, smooth appearance.\",\n \"The safety of Octyldodecanol and related ingredients has been assessed by the Cosmetic Ingredient Review (CIR) Expert Panel.\",\n \"The CIR Expert Panel evaluated the scientific data and concluded that octyldodecanol was safe for use in cosmetics and personal care products.\",\n \"In 2004, the CIR Expert Panel considered available new data on octyldodecanol and reaffirmed the above conclusion.\",\n \"Octyldodecanol may be used in cosmetics and personal care products marketed in Europe according to the general provisions of the Cosmetics Directive of the European Union.\",\n \"Cetyl alcohol (CAS No.\",\n \"36653-82-4) acts as an emollients, thickeners, and emulsifier.\",\n \"Cetyl alcohol and the other fatty alcohols keep an emulsion from separating into its oil and liquid components.\",\n \"These ingredients are also used to alter the thickness of liquid products and to increase foaming capacity or to stabilize foams.\",\n \"The safety of cetyl alcohol has been assessed by the Cosmetic Ingredient Review (CIR) Expert Panel.\",\n \"The CIR Expert Panel evaluated the scientific data and concluded that this fatty alcohol was safe for use as a cosmetic ingredient.\",\n \"In 2005, the CIR Expert Panel considered available new data on cetearyl alcohol and the other fatty alcohols and reaffirmed the above conclusion.\",\n \"If they are derived from plants, cetearyl, cetyl, isostearyl, myristyl and behenyl alcohols may be used in cosmetics and personal care products marketed in Europe according to the general provisions of the Cosmetics Directive of the European Union.\",\n \"Ingredients of animal origin must comply with European Union animal by-products regulations.\",\n \"Glyceryl stearate (CAS Nos.\",\n \"11099-07-3, 31566-31-1) may act as an emulsifier, humectant, lubricant, or solvent.\",\n \"As an emulsifier it assists in forming neutral, stable emulsions; it is also a solvent, humectant, and consistency regulator in water-in-oil and oil-in-water formulations.\",\n \"It is typically derived from palm kernel or soy oil for cosmetic use.\",\n \"Glyceryl stearate helps to form emulsions by reducing the surface tension of the substances to be emulsified.\",\n \"The safety of Glyceryl Stearate has been assessed by the Cosmetic Ingredient Review (CIR) Expert Panel.\",\n \"The CIR Expert Panel evaluated the scientific data and concluded that Glyceryl Stearate was safe form use in cosmetics and personal care products.\",\n \"The CIR Expert Panel reviewed chronic studies of glyceryl stearate that showed no adverse effects on reproduction, and no carcinogenic effects.\",\n \"Human exposure studies of products containing glyceryl stearate and glyceryl stearate SE, as well as clinical experience, have shown these compounds to be non-sensitizing, non-phototoxic and non-photosensitizing.\",\n \"If they are made from plants, glyceryl stearate and glyceryl stearate SE may be used in cosmetics and personal care products marketed in Europe according to the general provisions of the Cosmetics Directive of the European Union.\",\n \"Ingredients made from animal sources must comply with the European Union animal by-products regulations.\",\n \"A suitable material is available from Protameen Chemicals Inc. under the trade name “Protachem GMS-450.” Colloidal oat flour (CAS No.\",\n \"281-672-4) may act as a moisturizer, skin protectant, pH buffer, and anti-inflammatory agent, and may have anti-irritant and anti-inflammatory properties.\",\n \"As a skin protectant, colloidal oatmeal temporarily protects injured or exposed skin from harmful or annoying stimuli, and may therefore provide relief to the skin.\",\n \"Oatmeal has been used for centuries as a soothing agent to relieve itch and irritation associated with various xerotic dermatoses.\",\n \"In 1945, a ready to use colloidal oatmeal, produced by finely grinding the oat and boiling it to extract the colloidal material, became available.\",\n \"Today, colloidal oatmeal is available in various dosage forms from powders for the bath to shampoos, shaving gels, and moisturizing creams.\",\n \"Currently, the use of colloidal oatmeal as a skin protectant is regulated by the U.S. Food and Drug Administration (FDA) according to the Over-The-Counter Final Monograph for Skin Protectant Drug Products issued in June 2003.Its preparation is also standardized by the United States Pharmacopeia.\",\n \"The many clinical properties of colloidal oatmeal derive from its chemical polymorphism.\",\n \"The high concentration in starches and beta-glucan is responsible for the protective and water-holding functions of oat.\",\n \"The presence of different types of phenols confers antioxidant and anti-inflammatory activity.\",\n \"Some of the oat phenols are also strong ultraviolet absorbers.\",\n \"The cleansing activity of oat is mostly due to saponins.\",\n \"Its many functional properties make colloidal oatmeal a cleanser, moisturizer, buffer, as well as a soothing and protective anti-inflammatory agent.\",\n \"The Food and Drug Administration (FDA) reviewed the safety and efficacy of colloidal oatmeal and approved its use as an active ingredient in Over-the-Counter (OTC) skin protectant drug products at a minimum concentration of 0.007%, or 0.003% when used in combination with mineral oil.\",\n \"When used as a skin protectant in an OTC skin protectant drug product, this ingredient must be called colloidal oatmeal.\",\n \"The Cosmetic Ingredient Review (CIR) has deferred evaluation of this ingredient because the safety has been assessed by FDA.\",\n \"This deferral of review is according to the provisions of the CIR Procedures.\",\n \"Avena Sativa (Oat) Kernel Meal and colloidal oatmeal may be used in cosmetics and personal care products marketed in Europe according to the general provisions of the Cosmetics Directive of the European Union.\",\n \"Dimethicone (CAS No.\",\n \"9006-65-9) may act as a moisturizer and emollient.\",\n \"Dimethicone is a silicone based polymer that forms a protective barrier on the skin to help retain moisture.\",\n \"Dimethicone's oil-like consistency also gives it emollient properties.\",\n \"The Food and Drug Administration (FDA) reviewed the safety of dimethicone and approved its use as a skin protectant active ingredient in over-the-counter (OTC) drug products.\",\n \"The safety of Dimethicone has been assessed by the Cosmetic Ingredient Review (CIR) Expert Panel.\",\n \"The CIR Expert Panel evaluated the scientific data and concluded that these ingredients were safe for use in cosmetics.\",\n \"Dimethicone, methicone, and the related polymers may be used in cosmetics and personal care products marketed in Europe according to the general provisions of the Cosmetics Directive of the European Union.\",\n \"The World Health Organization Joint FAO/WHO Expert Committee on Food Additives has established an acceptable daily intake level for Dimethylpolysiloxane (Dimethicone) of 0 to 1.5 mg/kg body weight.\",\n \"PEG-40 stearate (CAS No.\",\n \"9004-99-3) may act as an emulsifier.\",\n \"PEG-40 stearate typically functions as a cleansing agent, but also helps keep ingredients solubilized.\",\n \"Suitable materials include a PEG-40 stearate available from Lipo Chemicals Inc. under the trade name “Lipopeg® 39S.”The safety of the PEG stearates has been assessed by the Cosmetic Ingredient Review (CIR) Expert Panel.\",\n \"The CIR Expert Panel evaluated the scientific data and concluded that PEG-2, -6, -8, -12, -20, -32, -40, -50, -100 and -150 stearates are safe for use in cosmetics and personal care products.\",\n \"In 2002, as part of the scheduled re-evaluation of ingredients, the CIR Expert Panel considered available new data on the PEG Stearates and reaffirmed the above conclusion.\",\n \"In the CIR Safety Review, the PEG stearates, whose average number of ethylene oxide monomers range from 2 to 150, were nonlethal at levels up to 10 g/kg.\",\n \"They gave evidence of only minimal skin irritation and minimal eye irritation when tested at 100%.\",\n \"PEG-8, -40 and -100 stearates produced no significant changes in growth, histopathologic observations or hematologic values in long-term feeding studies.\",\n \"Multiple generation studies of PEG-8 and -40 stearates were negative for effects on reproduction.\",\n \"Clinical studies on the PEG stearates indicated that these ingredients were neither irritants nor sensitizers at concentrations of 25% or greater.\",\n \"There was no evidence of phototoxicity or photosensitization of PEG-2 or -8 stearates.\",\n \"Because the smaller PEG stearates were not photosensitizing the CIR Expert Panel did not expect the larger ingredients to be photosensitizing.\",\n \"The CIR Expert Panel concluded that safety data on individual PEG stearates were sufficient for a decision regarding the safety of the entire group.\",\n \"Carbomer polymers may act a thickeners and formulation stabilizers.\",\n \"Carbomers are synthetic polymers of varying molecular weights that can be used to thicken suspend and stabilize cosmetic formulations.\",\n \"Requiring very low concentrations, carbomers are often used to adjust the viscosity of cosmetic preparations.\",\n \"They dry quickly and are not film forming.\",\n \"Carbomers as an ingredient family resist bacterial attack and do not readily support mold growth.\",\n \"Under normal conditions, gels prepared with sodium carbomer neither prevent nor promote the growth of microorganisms; therefore the addition of a suitable preservative system is advisable.\",\n \"The safety of the Carbomer has been assessed by the Cosmetic Ingredient Review (CIR) Expert Panel.\",\n \"The CIR Expert Panel evaluated the scientific data and concluded that carbomer polymers were safe as ingredients in cosmetics and personal care products.\",\n \"In 2001, as part of the scheduled re-evaluation of ingredients, the CIR Expert Panel considered available new data on carbomer polymers and reaffirmed the above conclusion.\",\n \"The CIR Expert Panel reviewed acute oral studies showing that carbomer polymers have low toxicities when ingested.\",\n \"Minimal skin irritation and no to moderate eye irritation were observed.\",\n \"Subchronic feeding studies with a carbomer polymer resulted in lower than normal body weights, but no abnormal changes were observed in the organs.\",\n \"Some gastrointestinal irritation and marked pigment deposition within specific cells in the liver, called Kupffer cells, were seen in studies with carbomer.\",\n \"Clinical studies with carbomers showed that these polymers have low potential for skin irritation and sensitization at concentrations up to 100%.\",\n \"A carbomer polymer demonstrated low potential for phototoxicity and photo-contact allergenicity.\",\n \"The Carbomers may be used in cosmetics and personal care products marketed in Europe according to the general provisions of the Cosmetics Directive of the European Union.\",\n \"Sodium Hydroxide (CAS No.\",\n \"1310-73-2) may function as a pH modulator, an alkali used to neutralize acids in maintenance of pH of the cream.\",\n \"The Food and Drug Administration (FDA) includes sodium hydroxide on its list of substances affirmed as Generally Recognized as Safe (GRAS) for direct addition to food.\",\n \"Sodium hydroxide, as well as calcium hydroxide, is also approved as an indirect food additive for use as a defoaming agent in the manufacture of paper and paperboard used as food packaging.\",\n \"Sodium hydroxide is listed in the Cosmetics Directive of the European Union (see Annex III) and may be used at the following concentrations and pH values: 5% by weight in nail cuticle solvents, 2% by weight in hair straighteners for general use, 4.5% by weight in hair straighteners for professional use, up to a pH 12.7 in depilatories, and up to pH 11 in other uses as a pH adjuster.\",\n \"The nail cuticle solvents and the general use hair straighteners containing these ingredients must be labeled “contains alkali, avoid contact with eyes, can cause blindness, keep out of reach of children.” The professional hair straighteners must be labeled “for professional use only, avoid contact with eyes, can cause blindness.” Depilatories containing these ingredients must include the following on the label: “Keep out of reach of children, avoid contact with eyes.” Phenoxy ethanol (CAS No.\",\n \"9004-78-8) may act as a preservative, anti-oxidant, or anti-microbial.\",\n \"Phenoxyethanol is used as a preservative in cosmetics.\",\n \"Phenoxyethanol prevents or retards microbial growth, and thus protects cosmetics and personal care products from spoilage.\",\n \"It may also be used in fragrances.\",\n \"Phenoxyethanol is usually synthesized for commercial use but it can also be found naturally in products such as green tea.\",\n \"The CIR Expert Panel reviewed safety data on phenoxyethanol and noted that it was practically nontoxic via oral and dermal administration.\",\n \"In a subchronic oral study, increased weights of some organs were noted when high doses of phenoxyethanol were administered.\",\n \"The doses in this study were considered to be much higher than those resulting from use of cosmetics and personal care products containing phenoxyethanol.\",\n \"In dermal laboratory studies, phenoxyethanol did not cause any birth defects.\",\n \"Phenoxyethanol was not mutagenic.\",\n \"In clinical studies, phenoxyethanol was neither a primary nor a cumulative irritant, it did not cause delayed hypersensitivity, and was it nonphototoxic.\",\n \"Phenoxyethanol is listed as 2-Phenoxyethanol in Annex VI, Part 1 (preservative which cosmetic products may contain) of the Cosmetics Directive of the European Union and may be used in concentrations up to 1%.\",\n \"Caramel Coloring III (CAS No.\",\n \"8028-89-5) is a coloring agent derived from heating edible sugar.\",\n \"In cosmetics and personal care products, caramel is used in the formulation of a wide variety of product types as a coloring agent.\",\n \"The Food and Drug Administration (FDA) includes caramel on its list of substances considered Generally Recognized As Safe (GRAS) as a multipurpose food substance.\",\n \"FDA also lists caramel as a color additive exempt from certification.\",\n \"Caramel is determined to be safe for use in coloring cosmetics and personal care products, including products applied to the lips and area of the eye.\",\n \"The Cosmetic Ingredient Review (CIR) has deferred evaluation of this ingredient because the safety has been assessed by FDA.\",\n \"This deferral of review is according to the provisions of the CIR Procedures.\",\n \"Caramel functions as a colorant in cosmetics and personal care products.\",\n \"To be used as a colorant in the United States, caramel must comply with FDA manufacturing requirements.\",\n \"For example, only certain food-grade acids, alkalis, and salts may be used to assist carmelization, in amounts consistent with good manufacturing practice.\",\n \"Caramel is listed in Annex IV, Part I (coloring agent allowed for use in cosmetic products) of the Cosmetics Directive of the European Union and may be used without restriction when purity requirements included in food regulations are fulfilled.\",\n \"DMDM Hydantoin (e.g., Glydant® Plus available from Lonza) may function as a preservative and anti-microbial.\",\n \"It is used as an antimicrobial formaldehyde releaser preservative with the trade name Glydant.\",\n \"DMDM hydantoin is an organic compound belonging to a class of compounds known as hydantoins.\",\n \"It is used in the cosmetics industry and found in products like shampoos, hair conditioners, hair gels and skin care products.\",\n \"DMDM hydantoin works as a preservative because the released formaldehyde makes the environment less favorable to the microorganisms.\",\n \"The Cosmetic Ingredient Review (CIR) Expert Panel has evaluated DMDM hydantoin and concluded that it was safe to a great majority of consumers but has limited the concentration to 0.2% free formaldehyde due to the skin sensitivity of some individuals to this agent.\",\n \"A study found “[a]n increase in the use of DMDM hydantoin in cosmetic products will also inevitably increase the risk of cosmetic dermatitis in consumers allergic to formaldehyde.\",\n \"The CIR Safety Review determined DMDM hydantoin is poorly absorbed from the skin.\",\n \"In a laboratory study, oral exposure to DMDM hydantoin did not result in any adverse effects.\",\n \"The CIR Expert Panel noted that DMDM hydantoin is a formaldehyde donor in aqueous media.\",\n \"They attributed positive results in some in vitro mutagenicity studies to formaldehyde release.\",\n \"In these studies, the concentrations of DMDM hydantoin tested were higher than those used in cosmetic and personal care products, likely resulting in much higher concentrations of formaldehyde than found in products.\",\n \"Clinical studies revealed some observations of skin irritation which could also be related to the release of formaldehyde from DMDM hydantoin.\",\n \"The CIR Expert Panel has reviewed the safety of formaldehyde in cosmetics and personal care products and concluded that it was safe to a great majority of consumers but has limited the concentration to 0.2% free formaldehyde due to the skin sensitivity of some individuals to this agent.\",\n \"The amount of DMDM hydantoin required to preserve a product (less than 1%) does not expose the consumer to concentrations of formaldehyde above the 0.2% limit for formaldehyde recommended by the CIR Expert Panel.\",\n \"DMDM hydantoin, called dimethylol, dimethylhydantoin [1,3-Bis(hydroxymethyl)-5,5-dimethylimidazolidine-2,4-dione], is listed in Annex VI, Part I (preservatives which cosmetics products may contain) of the Cosmetics Directive of the European Union and may be used in cosmetics and personal care products at a maximum concentration of 0.6%.\",\n \"If the concentration of released formaldehyde exceeds 0.05% in the finished product it must be labeled “contains formaldehyde.” Iodopropynyl Butylcarbamate (CAS No.\",\n \"55406-53-6) may function as a preservative, anti-microbial, and anti-fungal.\",\n \"The active ingredient of this product, IPBC, is recognized by the CTFA in the USA for use in cosmetic and personal care products and listed by the EU as an approved cosmetic preservative.\",\n \"IPBC-II is a colorless to light yellow, clear viscous liquid at room temperature.\",\n \"It is a unique and cost effective preservative that provides a high level of antimicrobial activity.\",\n \"It is remarkably proficient in inhibiting the growth of yeasts and molds.\",\n \"IPBC is compatible with essentially all cosmetic ingredients, such as surfactants, emulsifiers, proteins and herbal extracts.\",\n \"Methods of Preparation The compositions in general are prepared from the imidazole compound and colloidal oatmeal, as well as any other desired benefit agents.\",\n \"If desired additional ingredients such as surfactants and emulsifying agents, antihistamines, topical anesthetics, topical antipruritics, astringents, and emollients may be added.\",\n \"The ingredients may be added in such steps and amounts and processing varied as to create a spray, cream, gel, ointment, or lotion.\",\n \"The advantages of the invention and specific embodiments of the skin care compositions prepared in accordance with the present invention are illustrated by the following examples.\",\n \"It will be understood, however, that the invention is not confined to the specific limitations set forth in the individual examples, but rather defined within the scope of the appended claims.\",\n \"EXAMPLES Example 1 A topical formulation containing 100 mg of THI in 10 g of base cream was prepared as follows.\",\n \"To 1.0 g of base cream (water, glycerin, mineral oil, cetyl palmitate, caprylic/capric triglyceride, octyldodecanol, cetyl alcohol, glyceryl stearate, colloidal oat flour, dimethicone, PEG-40 stearate, carbomer, sodium hydroxide, phenoxy ethanol, caramel III coloring, DMDM hydantoin, iodopropynyl butylcarbamate) was added 100 mg of THI (CAS No.\",\n \"94944-70-4) portionwise with levigation of the powder between additions.\",\n \"A smooth cream was obtained by levigation in a marble mortar and pestle.\",\n \"A dime-sized portion of the levigated material was then incorporate geometrically with similar-sized portions of base and mixed thoroughly.\",\n \"Geometric mixing with additional cream base was repeated until 9.9 g of base was incorporated, yielding a 1.0% THI cream.\",\n \"Examination of the cream on a mixing plate suggested the THI was at least partially dissolving in the cream base.\",\n \"Application of the finished cream to the skin left no residue.\",\n \"Example 2 Eczema/Psoriasis Lotion Treatment The treatment test regime consists of three concentrations ranging from 0.5% to 2% of the active ingredient THI.\",\n \"Affected areas are documented with before and after photos and notes of observations from each step in the treatment regime are recorded.\",\n \"Three lotions respectively containing 0.5% (Disc “A”), 1.0% (Disc “B”), and 2% (Disc “C”) by weight of THI are used in the treatment test.\",\n \"Standard Application Protocol The area to which the lotion is to be applied to is cleaned before starting treatment.\",\n \"The lotion from Disc “A” is applied to just cover the affected area twice a day, once in morning and once again in evening.\",\n \"Any physical changes observed are noted; the treatment is discontinued if redness occurs.\",\n \"This regime is continued for one week.\",\n \"If the desired effect is realized at this concentration, applications at 0.5% concentration are continued without moving on to the next higher concentration.\",\n \"The treatment is discontinued if redness occurs.\",\n \"At the start of week two if no observed relief is noticed with 0.5% lotion from Disc “A”, treatment is begun with 1.0% lotion from Disc “B”.\",\n \"The application regime just described is repeated substituting the 1.0% lotion from disc “B” for one week.\",\n \"If the desired effect is realized at 1.0% concentration, the applications are continued at this concentration without moving on to the next higher concentration, Any physical changes observed are noted; the treatment is discontinued if redness occurs.\",\n \"At the start of week three if no observed relief is noticed with 1.0% lotion from Disc “B”, treatment is begun with 2.0% lotion from Disc “C”.\",\n \"The application regime just described is repeated substituting the 2.0% lotion from disc “C” for one week.\",\n \"If the desired effect is realized at 2.0% concentration, the applications are continued at this concentration.\",\n \"Any physical changes observed are noted; the treatment is discontinued if redness occurs.\",\n \"Example 3 Test Case for Excema The subject is a 10-year-old Caucasian male, in otherwise excellent health, suffering from excema over a portion of the subject's thighs.\",\n \"The subject rated the severity of the excema before treatment according to the protocol of Example 2 as 9 on a scale of 0 to 10, where 0 represents no psoriasis or excema, and 10 represents extremely bad psoriasis or excema.\",\n \"The subject had been previously treated with locoid lipid oil and hyderm topical hydrocortisone treatments with little to moderate success.\",\n \"The subject rated the effectiveness of the locoid lipid oil as 2 and of the hyderm cream as 4 on a scale of 1 to 5, where 1 represents an extremely useful treatment, and 5 represents no change in symptoms.\",\n \"After following the treatment protocol of Example 2 using only the 0.5% concentration lotion, the subject rated the severity of excema after treatment as 0.Example 4 Test Case for Psoriasis The subject is a 63-year-old Caucasian male, apparently in otherwise good health, suffering from psoriasis over a portion of the subject's chest and lower back.\",\n \"The subject had been suffering from moderate to severe psoriasis in these areas for more than 40 years and was able to obtain only moderate relief during that time from a variety of treatments including UV radiation, and at the time immediately prior to the treatment according to the protocol of Example 2 had been taking methotrexate orally and applying Daivonet or Daivonex ointments topically.\",\n \"Following the treatment protocol of Example 2 for two weeks and three weeks concluding with the 2.0% concentration lotion substantially relieved the subject's psoriatic symptoms.\"\n ]\n]"},"source":{"kind":"string","value":"Patent_15872027"}}},{"rowIdx":4493987,"cells":{"text":{"kind":"list like","value":[["INDUCTIVE VEHICLE","An inductively powered toy vehicle and an associated track with inductive charging segment.","The vehicle may include a secondary coil, a drive motor, an electrical power storage device connected between said secondary coil and said drive motor, and a wireless communications unit.","The charging segment may include a primary coil, a sense circuit operable to detect the presence of the vehicle based on a change in the detected impedance of the primary coil, and a power control unit operable to provide a time-varying current to the primary coil when the vehicle traverses the charging segment.","The primary coil is positioned within the race track adjacent the track upper surface.","The vehicle drive motor may be operable at first and second speed settings, and a remote control device can provide operating instructions to the vehicle wireless communications unit."],["1.A vehicle for traversing a charging circuitry having a primary coil configured to generate an inductive field, said vehicle comprising: a secondary coil; and a load electrically connected to said secondary coil; wherein said load receives electrical power from said secondary coil; wherein said vehicle is configured to perform an automated vehicle control action for a pre-set period of time based on a signal associated with the charging circuitry when proximate the charging circuitry.","2.The vehicle of claim 1 wherein said load includes an energy storage device, the vehicle further including a charge condition indicator to provide an indication based on the available charge remaining in said energy storage device.","3.The vehicle of claim 1 wherein said load includes a drive motor and an electrical power storage device electrically connected to said drive motor.","4.The vehicle of claim 3 wherein said drive motor is operable at a plurality of speed settings based on the signal associated with said charging circuitry.","5.The vehicle of claim 4 wherein said vehicle includes a sensor to detect said signal associated with said charging circuitry, said sensor being one of an electromagnetic sensor, a mechanical sensor, and an optical sensor.","6.The vehicle of claim 5 further including a microcontroller to regulate an operating parameter of said vehicle, said operating parameter including at least one of vehicle speed and vehicle steering.","7.A vehicle capable of traveling proximate an inductive charging station, said vehicle comprising: a controller; a secondary coil; and an electrical power storage device electrically connected to said secondary coil; wherein said controller is configured to initiate an automated vehicle control action based on a signal associated with the inductive power station, such that said vehicle performs said automated vehicle control action when proximate said inductive power station and such that said vehicle performs said automated vehicle control action for a pre-set period of time.","8.The vehicle of claim 7 including a display unit to provide an indication of a charge level remaining in said electrical energy storage device.","9.The vehicle of claim 7 including a drive motor electrically coupled to said electrical power storage device.","10.The vehicle of claim 9 wherein said vehicle is configured to deactivate said drive motor when said vehicle is proximate said inductive power station.","11.The vehicle of claim 7 wherein said automated vehicle control action includes changing the speed of said vehicle.","12.The vehicle of claim 7 including an RF circuit to receive the signal associated with said inductive power station, said RF circuit being separate from said secondary coil.","13.A vehicle for traversing a charging circuitry having a primary coil configured to generate an inductive field, said vehicle comprising: a secondary coil; a load electrically connected to said secondary coil; a sensor configured to sense a signal associated with the charging circuitry; a controller in electrical communication with said load, said controller configured to detect the charging circuitry based on the signal associated with the charging circuitry, and said controller configured to perform an automated vehicle control action for a pre-set period of time in response to said controller detecting the charging circuitry.","14.The vehicle of claim 13 wherein said sensor includes said secondary coil.","15.The vehicle of claim 13 wherein said sensor includes an RF circuit to receive the signal associated with said charging circuitry, said RF circuit being separate from said secondary coil.","16.The vehicle of claim 13 wherein said sensor includes one of an electromagnetic sensor, a mechanical sensor, and an optical sensor.","17.The vehicle of claim 13 wherein said automated vehicle control action includes changing speed of said vehicle.","18.The vehicle of claim 13 wherein said load includes a drive motor and an electrical power storage device electrically connected to said drive motor.","19.The vehicle of claim 18 wherein said drive motor is operable at a plurality of speed settings based on the signal associated with said charging circuitry.","20.The vehicle of claim 13 wherein said controller is configured to regulate an operating parameter of said vehicle, said operating parameter including at least one of vehicle speed and vehicle steering."],[" BACKGROUND OF THE INVENTION The present invention relates to providing inductive power to toy vehicles.","Electrically powered race track toys are known.","Some are intended for use on a grooved track surface, and are known as slot cars.","These toy vehicles or slot cars are designed for use on a segmented electrified track surface that is equipped with a slot, for accepting a guide pin attached to the car, and a pair of electrical contacts on either side of slot, also on the bottom of the car, for contacting matching wires embedded in the track to provide power to the car's electric motor.","Other cars are slot-less, and are retained on the track segments by curbs or walls on either side.","In the case of slot-less cars, most if not all of the track surface is equipped with electrical contacts to provide power to the car's electric motor.","The toy cars are typically controlled by a hand-held controller, which is connected by wire to the power supplied to the track.","By varying the electrical power, such as by a rheostat or digitally, the speed of the cars can be varied according to the user's discretion.","In the case of slot cars, steering is generally unavailable, as the slot and pin layout precludes deviation from the slot contained in the track.","In slot-less cars, some control may be available by varying the speed of the cars and by utilizing rudimentary steering inputs.","These toy cars, either slotted or slot-less, obtain electrical power required for motion from the track surface.","Thus, good electrical conductivity and physical contact is required throughout the entire track surface, or the cars may stop or perform erratically.","Consequently, the electrical contacts must normally be kept clean both on the track and on the cars.","As the tracks are often placed in dusty areas, such as a floor surface, and electricity attracts lint and other particles, such as dust, users are often required to clean the track and the contacts of the cars for good performance.","Another issue with the track segments involves the connection of the track segments to each other.","As the track forms a circuit to conduct electricity from each track segment to the next, a strong connection between segments is normally required.","The connection must normally provide considerable strength between adjacent track segments, but also remain easily detachable for track redesign or storage.","Over time, these contact areas between track segments can become worn and the conductivity degraded.","Additionally, the wires embedded in the track surface can oxidize while exposed to air, reducing the conductivity possible and reducing performance.","The user will normally clean the wires with an eraser or contact cleaner to remove the oxidation.","This is time-consuming and can be difficult, depending on the length of track to be cleaned.","A race track toy that addresses the issues discussed above and provides for more flexibility and user enjoyment is desired."],[" SUMMARY OF THE INVENTION The aforementioned problems are overcome by the present invention wherein a vehicle toy system eliminates electrical contacts on both the vehicle and the track, replacing them with inductive elements.","A wireless remote control allows users to operate the vehicle without an electrical connection.","One embodiment of the toy vehicle system of the present disclosure includes a track with at least one inductive coil charging portion, one or more toy vehicles, each with inductive coil charging equipment, one or more wireless controllers for operating the toy vehicles, and a power supply that provides power to the at least one inductive coil charging track portion.","Another embodiment of the present disclosure includes an inductive coil track portion that features a primary inductive coil in proximity to the track surface such that a vehicle coming into proximity of the surface receives an electrical charge.","Yet another embodiment of the present disclosure includes a toy vehicle with an inductive secondary coil for receiving electrical power from an inductive coil-equipped track segment.","Another embodiment of the present disclosure includes a toy vehicle with an inductive secondary coil for receiving electrical power from a source that is also connected to an electrical power storage device, such as a capacitor, a battery or the combination thereof.","Another embodiment of the present invention includes an inductive primary coil track segment that detects the presence of a toy vehicle by inductively pinging for the presence of a secondary inductive coil, such as contained within a toy vehicle or remote control device.","An embodiment of the present disclosure includes a toy vehicle with speed/throttle and/or steering controls broadcasting by a wireless control device to a receiver contained within the vehicle.","An embodiment of the present disclosure includes a toy vehicle operable at first and second speed settings based on a detected signal associated with a track, the vehicle including an electromagnetic sensor, a mechanical sensor, or an optical sensor.","An embodiment of the present disclosure includes a toy vehicle with steering operated by an electric relay device using wireless remote control.","An embodiment of the present disclosure includes a toy vehicle or remote controller with power level or other performance indicators, such as light emitting diodes (LEDs) to display information such as charge level remaining.","An embodiment of the present disclosure includes a toy vehicle with steering operated by an electric motor.","An embodiment of the present disclosure includes a toy vehicle with computer controls for monitoring performance, training purposes, and providing entertainment variables.","An embodiment of the present disclosure includes a track portion with a primary inductive coil.","The track portion may include a sensor to detect the presence of a vehicle, and provide power to the vehicle's onboard secondary coil.","Another embodiment of the present disclosure is a toy vehicle equipped with a secondary inductive coil, a primary inductive coil power station, and a remote control device for operating the toy vehicle.","These and other objects, advantages, and features of the invention will be more fully understood and appreciated by reference to the description of the current embodiment and the drawings.","It will be readily understood that the components of the present disclosure, as generally described and illustrated in the figures herein, may be arranged and designed in a wide variety of different configurations.","Thus, the following more detailed description of the embodiments of the apparatus, system, and method of the present disclosure, as represented in accompanying figures, is not intended to limit the scope of the disclosure, as claimed, but is merely representative of selected embodiments of the disclosure.","Reference throughout this specification to “one embodiment” or “an embodiment” (or similar) means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present disclosure.","Thus, appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment.","Furthermore, the described features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.","In the following description, numerous specific details are provided, such as examples, to provide a thorough understanding of embodiments of the present disclosure.","One skilled in the art will recognize, however, that the disclosure can be practiced without one or more of the specific details, or with other methods, components, materials, etc.","In other instances, well-known structures, materials, or operations are not shown or described in detail in order to avoid obscuring aspects of the disclosure.","The illustrated embodiments of the disclosure will be best understood by reference to the drawings, wherein like parts are designated by like numerals or other labels throughout.","The following description is intended only by way of example, and simply illustrates certain selected embodiments of devices, systems, and processes that are consistent with the disclosure as claimed herein."],["CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of U.S. Nonprovisional application Ser.","No.","14/023,730, entitled “INDUCTIVE SYSTEMS FOR VEHICLES”, filed Sep. 11, 2013, which is a continuation of U.S. Nonprovisional application Ser.","No.","12/622,465, entitled “INDUCTIVE TOY VEHICLE”, filed Nov. 20, 2009 (now U.S. Pat.","No.","8,545,284), which claims the benefit of U.S.","Provisional Application No.","61/116,908, filed Nov. 21, 2008, entitled “INDUCTIVE TOY VEHICLE.” BACKGROUND OF THE INVENTION The present invention relates to providing inductive power to toy vehicles.","Electrically powered race track toys are known.","Some are intended for use on a grooved track surface, and are known as slot cars.","These toy vehicles or slot cars are designed for use on a segmented electrified track surface that is equipped with a slot, for accepting a guide pin attached to the car, and a pair of electrical contacts on either side of slot, also on the bottom of the car, for contacting matching wires embedded in the track to provide power to the car's electric motor.","Other cars are slot-less, and are retained on the track segments by curbs or walls on either side.","In the case of slot-less cars, most if not all of the track surface is equipped with electrical contacts to provide power to the car's electric motor.","The toy cars are typically controlled by a hand-held controller, which is connected by wire to the power supplied to the track.","By varying the electrical power, such as by a rheostat or digitally, the speed of the cars can be varied according to the user's discretion.","In the case of slot cars, steering is generally unavailable, as the slot and pin layout precludes deviation from the slot contained in the track.","In slot-less cars, some control may be available by varying the speed of the cars and by utilizing rudimentary steering inputs.","These toy cars, either slotted or slot-less, obtain electrical power required for motion from the track surface.","Thus, good electrical conductivity and physical contact is required throughout the entire track surface, or the cars may stop or perform erratically.","Consequently, the electrical contacts must normally be kept clean both on the track and on the cars.","As the tracks are often placed in dusty areas, such as a floor surface, and electricity attracts lint and other particles, such as dust, users are often required to clean the track and the contacts of the cars for good performance.","Another issue with the track segments involves the connection of the track segments to each other.","As the track forms a circuit to conduct electricity from each track segment to the next, a strong connection between segments is normally required.","The connection must normally provide considerable strength between adjacent track segments, but also remain easily detachable for track redesign or storage.","Over time, these contact areas between track segments can become worn and the conductivity degraded.","Additionally, the wires embedded in the track surface can oxidize while exposed to air, reducing the conductivity possible and reducing performance.","The user will normally clean the wires with an eraser or contact cleaner to remove the oxidation.","This is time-consuming and can be difficult, depending on the length of track to be cleaned.","A race track toy that addresses the issues discussed above and provides for more flexibility and user enjoyment is desired.","SUMMARY OF THE INVENTION The aforementioned problems are overcome by the present invention wherein a vehicle toy system eliminates electrical contacts on both the vehicle and the track, replacing them with inductive elements.","A wireless remote control allows users to operate the vehicle without an electrical connection.","One embodiment of the toy vehicle system of the present disclosure includes a track with at least one inductive coil charging portion, one or more toy vehicles, each with inductive coil charging equipment, one or more wireless controllers for operating the toy vehicles, and a power supply that provides power to the at least one inductive coil charging track portion.","Another embodiment of the present disclosure includes an inductive coil track portion that features a primary inductive coil in proximity to the track surface such that a vehicle coming into proximity of the surface receives an electrical charge.","Yet another embodiment of the present disclosure includes a toy vehicle with an inductive secondary coil for receiving electrical power from an inductive coil-equipped track segment.","Another embodiment of the present disclosure includes a toy vehicle with an inductive secondary coil for receiving electrical power from a source that is also connected to an electrical power storage device, such as a capacitor, a battery or the combination thereof.","Another embodiment of the present invention includes an inductive primary coil track segment that detects the presence of a toy vehicle by inductively pinging for the presence of a secondary inductive coil, such as contained within a toy vehicle or remote control device.","An embodiment of the present disclosure includes a toy vehicle with speed/throttle and/or steering controls broadcasting by a wireless control device to a receiver contained within the vehicle.","An embodiment of the present disclosure includes a toy vehicle operable at first and second speed settings based on a detected signal associated with a track, the vehicle including an electromagnetic sensor, a mechanical sensor, or an optical sensor.","An embodiment of the present disclosure includes a toy vehicle with steering operated by an electric relay device using wireless remote control.","An embodiment of the present disclosure includes a toy vehicle or remote controller with power level or other performance indicators, such as light emitting diodes (LEDs) to display information such as charge level remaining.","An embodiment of the present disclosure includes a toy vehicle with steering operated by an electric motor.","An embodiment of the present disclosure includes a toy vehicle with computer controls for monitoring performance, training purposes, and providing entertainment variables.","An embodiment of the present disclosure includes a track portion with a primary inductive coil.","The track portion may include a sensor to detect the presence of a vehicle, and provide power to the vehicle's onboard secondary coil.","Another embodiment of the present disclosure is a toy vehicle equipped with a secondary inductive coil, a primary inductive coil power station, and a remote control device for operating the toy vehicle.","These and other objects, advantages, and features of the invention will be more fully understood and appreciated by reference to the description of the current embodiment and the drawings.","It will be readily understood that the components of the present disclosure, as generally described and illustrated in the figures herein, may be arranged and designed in a wide variety of different configurations.","Thus, the following more detailed description of the embodiments of the apparatus, system, and method of the present disclosure, as represented in accompanying figures, is not intended to limit the scope of the disclosure, as claimed, but is merely representative of selected embodiments of the disclosure.","Reference throughout this specification to “one embodiment” or “an embodiment” (or similar) means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present disclosure.","Thus, appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment.","Furthermore, the described features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.","In the following description, numerous specific details are provided, such as examples, to provide a thorough understanding of embodiments of the present disclosure.","One skilled in the art will recognize, however, that the disclosure can be practiced without one or more of the specific details, or with other methods, components, materials, etc.","In other instances, well-known structures, materials, or operations are not shown or described in detail in order to avoid obscuring aspects of the disclosure.","The illustrated embodiments of the disclosure will be best understood by reference to the drawings, wherein like parts are designated by like numerals or other labels throughout.","The following description is intended only by way of example, and simply illustrates certain selected embodiments of devices, systems, and processes that are consistent with the disclosure as claimed herein.","BRIEF DESCRIPTION OF THE DRAWINGS FIG.","1 is a perspective view of a track and associated toy vehicle in accordance with an embodiment of the present invention.","FIGS.","2A-D disclose a race track toy according to at least one embodiment of the present disclosure.","FIG.","3 discloses a race track toy according to at least one embodiment of the present disclosure.","FIGS.","4A-D disclose a plurality of race track toy embodiments.","FIGS.","5A-B disclose a toy vehicle according to at least one embodiment of the present disclosure.","FIG.","6 discloses a toy vehicle in accordance with at least one embodiment of the present invention.","FIG.","7 discloses a plurality of toy vehicles and remote controls according to at least one embodiment of the present disclosure.","FIG.","8 discloses a toy vehicle with secondary inductive coil and controls, and a track segment with primary inductive coil and power supply control system, according to at least one embodiment of the present disclosure.","FIG.","9 discloses a circuit diagram for an inductive power track segment with inductive sense circuit according to at least one embodiment of the present disclosure.","FIG.","10 discloses a circuit diagram for an inductive power track segment with proximity detector according to at least one embodiment of the present disclosure.","FIG.","11 discloses a circuit diagram for the inductive power track section with sense circuit using infrared (IR) modulation according to at least one embodiment of the present disclosure.","FIG.","12 discloses a circuit diagram for the present disclosure including a sense circuit using a magnetic interaction and a Hall Effect sensor according to at least one embodiment of the present disclosure.","FIG.","13 discloses a circuit diagram for the sense circuit using inductive coupling to determine a toy vehicle position near the primary charging coil according to at least one embodiment of the present disclosure.","FIG.","14 discloses a process flow diagram for enabling and disabling the charging circuit.","FIG.","15 discloses a process flow diagram for charging a car or a remote control on a segment of track equipped with a primary inductive coil according to at least one embodiment of the present disclosure.","FIG.","16 discloses a sensor sequence using an inductive sensor to turn power on and off in a primary inductive coil track segment according to at least one embodiment of the present disclosure.","FIG.","17 discloses a sensor sequence using light, IR or magnetic sensors to turn power in the track segment primary coil according to at least one embodiment of the present disclosure.","FIG.","18 discloses a sensor sequence using light, IR, or magnetic sensors to turn power on or off in the track segment primary coil according to at least one embodiment of the present disclosure.","FIG.","19 discloses a diagram of the interoperability between the toy vehicle and the remote controller, whereby the energy storage in both are inductively charged according to at least one embodiment of the present disclosure.","FIG.","20 discloses a diagram for the charging and energy storage system inside the toy vehicle according to at least one embodiment of the present disclosure.","FIG.","21 discloses a circuit diagram for the charging and energy storage system inside the toy vehicle including a protection switch and a diode according to at least one embodiment of the present disclosure.","FIG.","22 discloses a circuit diagram showing AC mains power being transformed and rectified to provide DC power to the wireless power supply to at least one embodiment of the present disclosure.","FIG.","23 discloses a circuit diagram illustrating multiple track segments with primary inductive coils that are monitored by a drive controller according to at least one embodiment of the present disclosure.","FIG.","24 discloses a circuit diagram illustrating multiple track segments with primary inductive coils that are monitored by multiple drive controllers according to at least one embodiment of the present disclosure.","FIG.","25 discloses a circuit diagram illustrating AC mains power being transformed and rectified to power multiple segments of track containing primary inductive coils according to at least one embodiment of the present disclosure.","FIG.","26 discloses a circuit diagram illustrating radio frequency (RF) communication of an inductive coil equipped track segment according to at least one embodiment of the present disclosure.","FIG.","27 discloses a circuit diagram illustrating a discrete drive and steering control of a vehicle and a remote controller according to at least one embodiment of the present disclosure.","FIG.","28 discloses a circuit diagram illustrating a continuous (proportional) control of drive and steering control of a car and a remote controller according to at least one embodiment of the present disclosure.","FIG.","29 discloses a toy vehicle and start/finish line containing inductive coils according to at least one embodiment of the present disclosure.","FIG.","30 discloses a toy vehicle and pit stop/gas station containing inductive coils according to at least one embodiment of the present disclosure.","FIG.","31 discloses a toy train and railroad containing inductive coils according to at least one embodiment of the present disclosure.","FIG.","32 discloses a boat and dock/poolside containing inductive coils according to at least one embodiment of the present disclosure.","FIG.","33 discloses a toy helicopter and landing pad containing inductive coils according to at least one embodiment of the present disclosure.","FIG.","34 discloses a toy aircraft and runway containing inductive coils according to at least one embodiment of the present disclosure.","DESCRIPTION OF THE CURRENT EMBODIMENT With reference to FIG.","1, a toy vehicle system including an inductively powered toy vehicle 40, at least one track segment 42, and an associated control module 44 is shown.","The vehicle 40 is drivable on a track including at least one segment 42 having a wireless power supply to generate an inductive field, wherein the vehicle 40 receives power from the inductive field when it traverses the track segment 42.Though shown as adapted for use on a circuit formed of multiple interconnected track segments 42, the toy vehicle 40 may also be used with only a single track segment 42 in combination with any suitable driving surface.","With reference to FIGS.","2A-2D, track segments 42 may be straight, curved, a combination of both, or other shapes, such as an intersection or a pit road track segment.","Plastic or other formable material may be used to construct the track segments, which optionally include connectors (not shown) to join other track segments together.","These connectors allow for a smooth transition surface or joint between the track segments so as to allow for the toy cars or vehicles to pass between sections unhindered.","Additionally, the optional connectors also allow for users to quickly disconnect the track segments to make alterations to the track layout or assemble a new circuit.","As shown in FIG.","2B, the track segment 42 is curved in a constant radius, to allow the vehicles to make a ninety degree turn.","Track segments 42 may be formed of any shape however, such as an intersection, sweeping curve, or other shape.","Optional lateral barriers or guard rails 43 may be used to contain the toy vehicles on the track surface, since the toy vehicles can be steerable and guide pins are unnecessary.","The guard rails 43 can help prevent vehicles from exiting the track segments 42, unless using specific segments equipped with exit ramps (not shown) where fences are omitted.","The track segments 42 can be easily presented in a circuit format as shown in FIG.","2C, where a number of straight and curved segments 42 or portions are arranged to form a circuit.","Using the integrated connectors of the track segments 42, a complete circuit 45 is shown in FIG.","1D, whereby vehicles may lap repeatedly without leaving the circuit 45 due to the guard rails 43.A track segment 42 with a primary inductive element 46 is shown in FIG.","3.The primary inductive element 46 can be any conductive element operable to produce a magnetic field when subject to a time-varying current, including a coil, for example.","A power and control unit 48 receives AC mains power from an external source (not shown), such as a wall outlet, and transforms and rectifies it to supply power to the track segment 42.At least one optional sensor 50, 52 is shown as a component to the track segment 42.The sensor 50, 52 can detect the presence of a vehicle entering and/or exiting the track segment 42.In one embodiment, a signal may be communicated from the sensor 50, 52 to the power and control unit 48 to power up the primary coil 46 if the sensor 50, 52 indicates that a vehicle is entering the track segment 42 and power down the primary coil 46 if a vehicle is leaving the segment 42.Additionally, the sensor 50, 52 may provide information for an optional race status display unit 54.The optional race status display unit 54 may display information such as the vehicle's lap speed and other performance parameters such as lap time, place, or other pertinent data.","Optionally, the vehicle 40 may be uniquely identified using specific resonant signals or other electronic marking, such as digital technology, and the display unit 54 can determine which vehicle has entered the track segment 42, or if multiple vehicles 40 enter, their places can be accurately determined.","The optional sensors 50, 52 may be embedded within the track surface 56, side rails 42, or attachable using a fastening method, such as snap-on or adhesive.","In this way, additional sensors 50, 52 can be placed about the track 45 to measure performance in portions of a circuit, such as a racing training aid or performance meter.","While one primary inductive coil 46 is shown in a track segment 42 in FIG.","3, multiple primary coils may be included in a track segment 42 or other application suitable for coil shapes, such as a pad, start/finish line, or other suitable surface for engagement with a vehicle.","For example, a plurality of primary coils arranged in a staggered pattern or an array of coils allows for power to be transferred to vehicles with secondary coils in a number of variations.","FIGS.","4A-D are illustrations of various race track arrangements.","A primary inductive coil segment or charging portion 56 is shown as a part of a race track circuit 44.For illustrative purposes only, an oval is shown; however a circuit of any shape may be constructed.","The primary inductive coil segment 56 is connected to a power, control, and race status unit 58 which provides mains power and optionally processes race car performance data from the sensors (not shown) included in the track segment(s) 56.In another embodiment as shown in FIG.","4B, two primary inductive coil segments 56 are shown as a portion of a race track circuit 45.For both segments 56, power, control, and race status unit connections may be provided.","In another embodiment as shown in FIG.","4C, three primary inductive coil segments 56 are shown as a portion of a race track circuit 45, each may be provided with connection to the power, control, and race status unit 58.In yet another embodiment as shown in FIG.","4D, four primary inductive coil segments 56 are shown as a portion of a race track circuit 45, each provided with connection to the power and race and control unit 58.By utilizing multiple primary coil track segments 56, the toy vehicle 40, for example a race car 60, may receive additional charging opportunities; data may be gathered about their performance in multiple sections of the track, as well as other performance or entertainment data.","For example, one primary coil segment 56 could be located in a pit area, such that a vehicle 40 may pause and “refuel” by charging inductively.","Additionally, the control unit may retain a vehicle 40 in a segment 42 by sending a signal to the vehicle to deactivate it for a period of time, such as to serve a penalty or “black flag”.","Another feature of the present disclosure is the adaptability of the track segments 56 with inductive coils 46 to be equipped with adapters for use with other existing and future track circuits and vehicles, or as a stand-alone additional accessory for vehicles not requiring a track circuit.","For example, an adapter attached to a track segment with inductive coils may be inserted into a track system, allowing for vehicles equipped with inductive secondary coils to use the track circuit.","Further, the remote controllers may also receive charging from the inductive track segment 56 due to their own on-board secondary coils.","FIGS.","5A-B are illustrations of a race car 60 according to at least one embodiment of the disclosure.","As shown in FIG.","5A, the race car 60 can include a body shell 62 and chassis 64 with various components.","FIG.","5B shows the race car 60 with the body shell 62 removed, revealing the chassis 64 with various components.","The drive motor 66 is shown, which is equipped with a gear that engages a second gear located on a drive shaft, connected to a pair of wheels.","Note that in this embodiment, the rear wheels of the race car 60 are the drive wheels, but in other embodiments, the race car 60 may have front wheel drive or all-wheel drive.","Additionally, other means of providing power to the wheels may be used, such as a belt drive system, or individual motors may be located at some or all of the wheels.","On the bottom of the chassis 64 is the secondary inductive element 68, which selectively receives electrical power when in proximity to a track segment 42 containing a primary inductive coil 46.The secondary inductive element 68 can be any conducting element adapted to generate a current when subject to a time-varying magnetic field, including a secondary coil, for example.","The energy storage system 70 is shown in the middle portion of the chassis 64 in this embodiment, but may be located elsewhere on the chassis 64.As the coil 68 is energized, electrical power is transferred to the energy storage system 70, which may include a battery, a capacitor, a combination of both, or another suitable energy storage device.","A microcontroller 72 includes an RF receiver or other wireless communications device and is optionally located on the chassis 64.The microcontroller 72 receives signals from a control unit (not shown) which is operated by the user, by the track control unit, or by internal control circuitry, such as a pace car or training aid.","The microcontroller 72 can regulate the race car speed, steering, and other control features, such as lights.","In the current embodiment, the steering mechanism 74 includes a relay, servomotor, or other means for changing the front wheel direction so as to allow the user to steer the race car 60.Additionally, the rear or all wheels may also feature steering for additional performance.","As shown in FIG.","6, the secondary coil 68 can optionally extend beyond the length and width of the wheel base of the car 60, or circumferentially encompass the each of the four tractive wheels.","This configuration can achieve an enhanced transfer of power, with the secondary coil 68 optionally functioning as a bumper for the car 60 during racing.","FIG.","7 illustrates a race car controller 76 and a race car 60.Additional race cars 78 may be controlled by additional controllers 80 with complimentary, non-interfering, independent wireless communication.","A controller 76 is shown with a number of control options, such as speed setting, steering, and braking.","Other, different, or fewer controls may also be included, such as a graphic display providing car data, light control, battery power remaining in the car and controller, as well as other features.","A wireless link may be established between the controller 76 and race car 60.This link allows for the user to operate or drive the car 60 around a track circuit 45 or outside of a track circuit 45 if desired.","The car 60 may be recharged by driving it onto or over a primary coil track segment 56 or other embodiment of a track segment, such as a pit stop or gas station (not shown).","The wireless communication may be RF, infrared, Bluetooth, or some other wireless communication method.","Optionally, the controller 76 may include variable speed control and continuous steering control instead of discrete steering inputs.","FIG.","8 is a cutaway view of a toy race car 60 including a secondary inductive coil 68 located on the car chassis 64, which receives energy and transfers it to storage device 70.The energy may be rectified in an optional rectify unit 82.A power control 84 and a microcontroller 86 receive energy from the storage device 70, which may be a battery, capacitor, combination of both or other suitable energy storage device.","An RF communications circuit 88 receives energy from power control 84 and the microcontroller 86, and can receive and transmit wireless signals to the user controller (not shown) to operate the race car 60.A Drive and Speed FWD/REV unit 90 is shown, which in this embodiment is the rear drive wheels, including an electric motor and gear system.","Steering control 92 is shown at the front of the race car 60, which receives signals from the microcontroller 86, which in turn receives signal commands from the user remote control (not shown) as to which direction the user desires the race car to move.","An ID unit 94 is shown within the race car 60, which includes unique car information that may be transmitted to the race track power and race control unit (not shown).","Such ID information could include type of vehicle, performance level, driver ID, or other information.","The drive motor 66 can be operated at multiple speed settings based on a detected signal associated with a portion of the track 45.For example, a first speed setting could be set by the vehicle microcontroller 86 to prevent the drive motor 66 from draining the energy storage device 70 to quickly.","A second speed setting could be set by the microcontroller 86 to provide increased vehicle speed during short intervals in which increased vehicle speed is desired, e.g., in a run-up to a ramp or loop.","The microcontroller 86 can switch between speed settings in response to a signal associated with a portion of the track 45, for example, an inductively powered track segment 56.Upon receiving the signal, optionally through the secondary coil 68 or the RF circuit 88, the microcontroller 86 could control the drive motor to increase or decrease the power drawn from the storage device 70.The change in drive motor control could be momentary (i.e., pre-set for a period of time) or permanent (i.e., continuing until a second signal is detected during the course of the vehicle's movement about the track).","As discussed in greater detail below, the signal can also be generated by a magnet in combination with a Hall Effect sensor, an LED in combination with a photodiode, or a mechanical switch in combination with an actuator, for example.","As also shown in FIG.","8, a wireless power supply 106 including a primary inductive coil 46 is shown embedded in a track segment 42.An inverter 96 is shown connected to the primary coil 46, as well as a microcontroller 98, which, in the current embodiment, receives signals from the sense circuit 100 to activate when the race car 60 is in proximity to the track segment 42.A DC/DC converter 102 is connected to the inverter 96 and microcontroller 98 and receives power from a DC input 104.As shown in FIG.","9, the sense circuit 100 can be an inductive sense circuit 108.Power is supplied by mains input 110, which is then rectified by mains rectifier 112.The inductive sense circuit 108 monitors the impedance of the primary coil 46 and generates a signal which is analyzed by the control unit 114 to determine if a vehicle 40, for example a race car 60, is in the proximity of the primary coil 46.The inductive sense circuit 108 may also determine the identity of the race car 60 and monitor performance.","The performance information can also be used to monitor lap counts and race status, for example.","Rectified power is sent through the DC/DC converter 116 and the inverter 118 which energizes the inductive coil 68 if a race car 60 is in proximity.","In another embodiment as shown in FIG.","10, the sense circuit 100 can be a vehicle proximity sense circuit or proximity detector 120.By using a proximity detector 120, energy is conserved by only energizing the primary coil 46 within the track segment 42 when a race car 60 is in proximity, e.g., when the race car 60 traverses the track segment 42.Additionally, the activating of the proximity detector 120 may be used to record laps or other performance data due to the unique identification of each vehicle.","Power is supplied by mains input 110, which is then rectified by the mains rectifier 112.The proximity detector 120 determines if a vehicle is in proximity and generates a signal which is analyzed by the control unit 114.Rectified power is sent through the DC/DC converter 116 and the inverter 118 which energizes the primary inductive coil 46 if a vehicle is in proximity.","FIG.","11 is a block diagram of one embodiment of a sense circuit 100 using IR or wireless modulation, such as shown in FIG.","8.An IR or other wireless transmitter 122 is located on a race car 60, which transmits a signal to the sense circuit 100.An IR or wireless sensor and demodulator 124 receives the signal, which is amplified by amplifier 126 before being sent to signal conditioner 128, which sends an output signal to the control unit (not shown) and receives power from the rectifier (not shown).","Each race car 60 may be equipped with an IR transmitter or other wireless transmitter 122 which emits an encoded unique signal which is detected when the car 60 is present near the sense circuit 100, such as may be located in a primary inductive coil track segment 56.Information encoded on the transmitted signal is used to identify the car, its performance, or other information.","Additionally, optical sensors such as photoelectric eyes may also be used.","FIG.","12 is a block diagram of one embodiment of a Hall Effect proximity sense circuit 100 such as shown in FIG.","8.A magnet 130 is located on each race car 60.The Hall Effect sensor 132 differentiates between particular cars based on the unique magnetic signal of each magnet 130 onboard each car.","An arrangement of different sizes and polar orientations of the magnets 130 allows for multitudes of combinations for car identification.","The signal generated by the Hall Effect sensor 132 enters the amplifier 126 before being passed to the signal conditioner 128, which outputs the signal to the control unit (not shown) and receives power from the rectifier (not shown).","FIG.","13 is a block diagram of an inductive sense circuit 108 showing a race car 60 or remote control 76, either of which being equipped with a secondary inductive coil 68 in proximity to the primary coil 46.The primary coil 46 may be located in a track segment 42 or other suitable location, such as a charging station or holster, or a pit garage location.","The inductive sensor and signal generator 134 detects the presence of a load 68 in proximity to the primary coil 46, optionally based on a change the detected impedance of the primary coil when the car 60 is proximate the inductive track segment 56, and sends a signal to the amplifier 126, which then passes the amplified signal to the signal conditioner 128 for output to the control unit (not shown) as the sense circuit 108 continues to receive power from the rectifier (not shown).","FIG.","14 illustrates a process flow diagram describing one embodiment of a race car or remote charge sequence.","The primary coil 46 with sensor unit 100, such as enclosed within a track section 42, determines whether a car 60 is present, using a motion sensor 120 or inductive sense circuit 108.If no car is present, the primary coil 46 remains de-energized.","If a car or remote is present, however, the control unit is powered up, which using sensors determines the car identity, speed, and other data, and transmits the data to the power and race control unit 58.Power is then applied to the primary coil 46 for the period the car 60 is present.","Once the race car 60 has passed out of the presence of the primary coil 46, or a foreign object is detected, the primary coil 46 is de-energized until another race car 60 enters the proximity of the primary coil 46.Accordingly, the primary coil 46 provides wireless power to the car 60 in increments corresponding to successive traversals of the inductive charging segment 56 by the race car.","FIG.","15 is a process flow diagram describing another embodiment of a race car or remote charge sequence.","The primary coil 46 with sensor unit 100, such as enclosed within a track section 42, determines whether a car 60 or remote control is present, using a motion sensor 120 or inductive sense circuit 108.If no car 60 or remote 76 is present, the primary coil 46 remains de-energized.","If a car 60 or remote 76 is present, however, the control unit 114 is powered up, which using sensors determines the car identity, speed, and other data, and transmits the data to the power and race control unit 58.Power is then applied to the primary coil 46 for the period the car 60 or remote 76 is present.","Once the race car 60 has passed out of the presence of the primary coil 46, the remote 76 is removed, or a foreign object is detected, the primary coil 46 is de-energized until another race car 60 or remote 76 enters the proximity of the primary coil 46, or until the foreign object is removed.","Accordingly, the primary coil 46 provides wireless power to the car 60 in increments corresponding to successive traversals of the inductive charging segment 56 by the race car.","FIG.","16 is a graph of one embodiment of a sensor sequence using an inductive sensor to energize and de-energize a primary inductor coil.","In section A, the inductive sensor 134 periodically checks for the presence of a race car 60.As the car 60 enters the range of the sensor 134, the inductive sensor 134 detects the presence of a load 68 and activates the primary coil 46, energizing it to provide power to the race car 60.Once the race car 60 has passed out of the range of the inductive sensor 134, the primary coil 46 is deactivated and the inductive sensor 134 returns to a periodic checking mode, until the next race car 60 enters the range of the inductive sensor 134.FIG.","17 is a graph of one embodiment of a sensor sequence with using various sensing techniques, including light, IR, magnetic sensors, or other wireless communication.","As a race car approaches a sensor, it is wirelessly detected, and the sensor signal is communicated to the control unit which energizes the primary coil located in a track segment, for example.","The sensor continues to detect the presence of the car, and maintains the signal sent to the control unit.","FIG.","18 is a graph of one embodiment of a sensor sequence with using various sensing techniques, including light, IR, magnetic sensors, or other wireless communication.","As a race car approaches a sensor, it is wirelessly detected, and the sensor signal is communicated to the control unit which energizes the primary coil located in a track segment, for example.","The sensor continues to detect the presence of the car, and maintains the signal sent to the control unit.","After a period of time, the car departs the range of the sensor, and primary coil is de-energized.","FIG.","19 is a block diagram illustrating the interoperability of an inductive wireless power supply 106, a toy vehicle 40, and a vehicle controller 76.As described above in connection with FIG.","14, the wireless power supply 106 can include a DC/DC converter 116 connected to an inverter 118 and microcontroller 98 and receives power from a DC input 104.The wireless power supply 106 is shown as including an inductive sense circuit 108, but can also include a proximity detector 120 as explained above in connection with FIG.","10.The toy vehicle 40 and remote control 76 can each include an inductive secondary 68, a rectify and charge control circuit 85 as described above in connection with FIG.","9, and a vehicle energy storage unit 70.In operation, the wireless power supply 106 provides a varying magnetic field to induce an alternating current in the respective secondary coils 68 of the toy vehicle 40 and remote control 76.Once rectified by the rectifier and charge control circuit 85, current supplied by the secondary coil can be stored in the energy storage unit 70.As shown in FIG.","20, the vehicle energy storage device can include a charge control unit 136, a storage device 138 and a protection/regulation device 140.The storage device 138 can include a battery, capacitor, combination of both, or other storage device.","The voltage is conditioned to the appropriate values for the subsequent circuit elements in the protection/regulation device 140.Output signals are produced by the protection/regulation device 140 which indicate the charge state of storage device 138 and are sent to the car control unit (not shown).","As shown in FIG.","21, the vehicle energy storage unit 70 includes a protection switch 142 and diode 144 after the voltage input point.","The switch 142 allows for the isolation of the energy storage circuit 70 if so desired and the diode 144 constrains flow only into the charge control circuit block.","FIG.","22 is one embodiment of a circuit diagram of AC mains power being transformed and rectified in the DC power supply 146, which using a cable 148, can be remotely located from the wireless race track power supply 106, allowing for large track circuits and freedom from mains power outlet locations.","FIG.","23 is one embodiment of a circuit diagram illustrating multiple inductive track segments 56 being monitored, powered and controlled by a single drive controller 114.Mains voltage 110 is supplied to the wireless power supply 106.As the voltage enters the power supply, it first passes to the rectifier 112, after which the sense circuit 100 monitors the presence of race cars (or other secondary coil-equipped devices) at multiple track segments.","A single drive control unit 114 is connected to the multiple track segments, each with its own primary coil 46.As race cars enter the proximity of the various coils, the sense circuit detects their load and allows for power to the supplied to the particular coil where a car is present, for the period that the car is present.","FIG.","24 is a circuit diagram illustrating multiple inductive track segments 56 being monitored, powered and controlled by multiple drive controllers 114.Mains voltage 110 is supplied to the wireless power supply 106.As the power enters the power supply, it first passes to the rectifier 112, after which the sense circuit 100 monitors the presence of race cars (or other secondary coil-equipped devices) at multiple track segments.","Multiple drive control units 114 are connected to the multiple track segments, each with its own primary coil 46.As race cars enter the proximity of the various coils, the sense circuit detects their load and allows for power to the supplied to the particular coil where a car is present, for the period that the car is present.","FIG.","25 is a circuit diagram illustrating mains power being transformed and rectified to power multiple inductive track segments, including the separation of the mains rectification and the DC/DC conversion from the remainder of the race track using a cable.","Mains voltage is supplied to the DC power supply 146, containing a rectifier and a DC/DC converter.","Connected to the DC power supply is cable 148, which allows for separation of the DC power supply and the wireless power supply 106, which includes an internal power supply 150, connected to a sense and sense control unit 100, which monitors the presence of race cars (or other secondary coil-equipped devices) at multiple track segments.","Multiple drive control units 114 are connected to the multiple track segments, each with its own primary coil 46.As the voltage enters the power supply, it first passes to the rectifier 112, after which the sense circuit 100 monitors the presence of race cars (or other secondary coil-equipped devices) at multiple track segments.","Multiple drive control units 114 are connected to the multiple track segments, each with its own primary coil 46.As race cars enter the proximity of the various coils, the sense circuit detects their load and allows for power to the supplied to the particular coil where a car is present, for the period that the car is present.","FIG.","26 is a circuit diagram illustrating one embodiment of RF remote communication of the inductive segments of race track, which allows for wireless control of the power supply and communication between the components.","A remote control unit 76 includes an input and control interface 153, a stored power device 70, such as a battery, and a RF or wireless circuit 152, which is connected to an optional antenna 154.The remote control unit 76 communicates with the wireless power supply 106 using RF, infrared, Bluetooth or other type of wireless communication.","Mains power is supplied to the wireless power supply.","There, mains power is supplied to the RF/wireless communications circuit 156, though DC power may also be used.","Mains power is rectified by the rectifier 112, after which the output is monitored by the power supply control unit 114 and the sense circuit 100, which also is connected to the RF communications circuit.","The DC/DC converter processes the rectified power and sends it to the inverter 118, after which the power is sent to the primary coil 46, which is located in a track segment 42 or other suitable location.","The remote control 76, toy vehicle 40, or inductive track segment 56 can include a charge condition indicator (not shown) to provide an indication based on the available charge remaining in a storage device 70 in either of the remote control 76 or toy vehicle 40.FIG.","27 discloses a circuit diagram illustrating a discrete drive and steering control of a car and a remote controller 76.Within the controller is a RF transmit and receive circuit 152, connected to an input and control interface 153, which features operational controls, such as forward/reverse, turn right/left, and other vehicle controls.","The remote controller 76 is powered by a stored power device 70, which may be a battery, a capacitor, a combination of both, or another suitable power storage device.","The remote controller 76 also includes an antenna 154, which may be external or internal.","The car drive control circuit 170 is located within a vehicle (not shown) and includes a charge storage device, which may be a battery, a capacitor, a combination of both, or another suitable power storage device.","The charge storage device 156 is connected to a DC/DC converter 160, which provides power to the RF transmit and receive circuit 158.Signals from the circuit 158 are relayed to the microcontroller 86, which also is powered by the DC/DC converter 160.The microcontroller controls the steering control voltage unit 162 and the wheel drive voltage unit 164.The drive motor 168 receives regulated voltage from the wheel drive voltage unit resulting in varying vehicle speed according to user input on the remote controller 76.The steering solenoid 166 receives regulated voltage from the steering control voltage unit 162 resulting in varying vehicle direction according to user input on the remote controller 76.As noted above in connection with FIG.","26, the remote control 76, toy vehicle 40, or inductive track segment 56 can include a charge condition indicator (not shown) to provide an indication based on the available charge remaining in a storage device 70 in either of the remote control 76 or toy vehicle 40.FIG.","28 discloses a circuit diagram illustrating a continuous (proportional) control of drive and steering control of a car 60 and a remote controller 76.Within the controller is a RF transmit and receive circuit 152, connected an input and control interface 153, which features operational controls, such as forward/reverse, turn right/left, and other vehicle controls.","The remote controller is powered by a stored power device 70, which may be a battery, a capacitor, a combination of both, or another suitable power storage device.","The remote controller 76 also includes an antenna 154, which may be external or internal.","The car drive control circuit 170 is located within a vehicle (not shown) and includes a charge storage device, which may be a battery, a capacitor, a combination of both, or another suitable power storage device.","The charge storage device is connected to a DC/DC converter 160, which provides power to the RF transmit and receive circuit 158.Signals from the circuit 158 are relayed to the microcontroller 86, which also is powered by the DC/DC converter.","The microcontroller controls the proportional steering control voltage unit 172 and the proportional wheel drive voltage unit 174.The drive motor 168 receives regulated voltage from the wheel drive voltage unit resulting in varying vehicle speed according to user input on the remote controller 76.The steering solenoid 166 receives regulated voltage from the proportional steering control voltage unit 172 resulting in varying vehicle direction according to user input on the remote controller 76.FIG.","29 discloses one embodiment of an inductive charging segment 56 including start/finish line 200 with a power supply 202 and a primary inductive coil (not shown) located within the start/finish line.","A car 60 containing a secondary inductive coil 68 and control system (not shown) is controlled by a wireless remote controller (not shown), also containing a secondary coil, operated by a user.","As the user drives the car 60 across the start/finish line 200, a charge is received by the vehicle's secondary coil 68 and is stored by the vehicle's onboard storage device.","This charge allows for the vehicle to continue operating.","For example, a user can position the start/finish line 200 in an area and create a custom race circuit, or simply place the start/finish line 200 in an area that the user decides to operate the vehicle.","A display (not shown) contained on the start/finish line 200 and/or the vehicle 60 and its controller provide the user with charge level information.","Optionally, the charging segment 56 can include one or more ramps or inclines 203 extending from the lateral edges of the charging segment 56 to permit a car 60 to drive onto and off of the charging segment 56.FIG.","30 discloses a charging segment 56 including a charge station or pit stop 204 with a power supply 202 and a primary inductive coil (not shown) located within the pit stop 204.A car 60 containing a secondary inductive coil 68 and control system (not shown) is controlled by a wireless remote controller (not shown), also containing a secondary coil, operated by a user.","As the user drives the car 60 across the pit stop 204, a charge is received by the vehicle's secondary coil 68 and is stored by the vehicle's onboard storage device.","This charge allows for the car 60 to continue operating.","For example, a user can position the pit stop 204 in an area and create a custom race circuit, or simply place the pit stop in an area that the user decides to operate the car 60.A display (not shown) contained on the pit stop 204 and/or the car 60 and its controller provide the user with charge level information.","A suitable decoration such as a gas pump 206 may be used to identify the charging location.","Optionally, the charging segment 56 can include one or more ramps or inclines 203 extending from the lateral edges of the charging segment 56 to permit a car 60 to drive onto and off of the charging segment 56.Though described above in connection with a race car moveable along a toy race track, the present invention can also be incorporated in other toy vehicles, including a toy train 192, a toy boat 194, a toy helicopter 196, or toy airplane 198, for example.","As shown in FIG.","31, the present invention can include a train 192 moveable along a railroad track 176 equipped with a primary inductive coil 46.Onboard the train is a wireless control unit 170 according to the present disclosure, and powering the railroad track primary coil is a power and control unit according to the present disclosure.","As the user controls the train 192, it moves over the inductive coil 46 incorporated into the railroad track section.","In doing so, a charge is received by the secondary coil 68 onboard the train 192, which is stored in a suitable storage device.","The train's electric motor then powers the train about the railroad circuit, and receives another charge when it passes over the primary coil equipped track segment again.","In this embodiment, a train engine, railroad car, trolley, or other rolling stock may be equipped with secondary coils, energy storage devices, and other controls which may be wirelessly controlled by the user, or automatic in operation.","Additionally, as disclosed above, a wireless remote control device equipped with a secondary coil and energy storage device is used to control the train, though a traditional power supply may also be used, to send digital signals through the track while power is supplied by inductive coil.","In another embodiment, the primary inductive coil 46 may be incorporated in other railroad accoutrements, such as buildings, landscaping or the rail bed.","Locating inductive coils about a train layout provides power to buildings, street lights, and other decorations without traditional wiring.","As shown in FIG.","32, the inductively powered vehicle can include a motorized boat 194 having a secondary coil 68 and control system 170 as disclosed above.","The boat 194 can be controlled by a wireless remote controller 76 including a secondary coil 68, and the primary inductive coil 46 and associated power supply system circuitry 106 can be incorporated into a portion of a dock or a portion of a poolside 178, for example.","As a user operates the boat 194 via the remote controller 76, the boat 194 and/or controller 76 can include a charge condition indicator (not shown) to display the charge level remaining in the boat's onboard energy storage device and control system (not shown) as disclosed above.","The display can allow a user to determine when to approach the primary coil equipped portion of the dock or pool side 178.The user can move the boat 194 from that location when the vessel is fully charged, or leave early if desired.","In order to maintain a proximity to the primary coil equipped portion 178, a magnet 180 or other restraining device may be used, which may be positioned to prevent the boat 40 from departing until a full charge is received, for example.","FIG.","33 discloses a helicopter 196 with a secondary inductive coil 68 and control system 170 as disclosed above.","The helicopter 196 is controlled by a wireless remote controller (not shown), also with a secondary inductive coil.","A primary inductive coil 46 and power supply system is incorporated into a landing pad 182 or other suitable object.","A user flies the helicopter 196 using the remote controller, and lands it on the landing pad 182 to receive a charge.","The controller and/or helicopter 196 provide the user with charge level status.","When the user desires, and the helicopter has sufficient charge, it may lift off and resume flight at the user's discretion.","The primary coil 46 may be located in other objects aside from a landing pad, such as a target incorporated into a flying game.","FIG.","34 discloses an airplane 198 with a secondary inductive coil 68 and control system as disclosed above.","The aircraft 40 is controlled by a wireless remote controller, also with a secondary inductive coil (not shown).","A primary inductive coil 46 and power supply system is incorporated into a runway 184 or other suitable object.","The user flies the airplane 198 using the controller and lands on the runway 184 for a charge.","The controller and/or aircraft 198 provide the user with charge level status.","When the user desires, and the aircraft 198 has sufficient charge, it may lift off and resume flight at the user's discretion.","The primary coil 46 may be incorporated into other aviation-related objects, such as a taxiway or aircraft carrier.","Accordingly, additional vehicles may utilize the inductive charging technology as detailed above.","For example, toy aircraft such as helicopters or airplanes may be equipped with inductive coils and energy storage devices, along with control systems.","A landing pad or runway may also be equipped with a primary inductive coil and power supply, enabling a user to land a craft on such a surface, similar to the track segments as in the race track, and receive a charge for the onboard storage energy storage device.","The user can then command the craft to takeoff, using a wireless remote control, and enjoy another electrically-powered flight.","Trains may also be equipped with inductive charging technology.","For example, a locomotive may include an inductive coil, energy storage device, and control system, and a railroad segment may include a primary coil and power supply.","A user, with a control unit, can command the train to move onto the segment, receiving a charge stored onboard.","This segment could be, for example, a train station, coaling depot, or a plurality of segments spaced about a train track layout, each providing a charge to the train locomotive, or other cars being pulled by the train.","Motor boats may also be equipped with inductive charging technology.","A boat with a secondary coil can approach a dock, for example, which may include a securing device, such as a magnet, for holding the boat to the dock.","Within the dock is a primary coil and power supply.","The boat, when fully charged, is released by the dock or the user, and is able to drive about the surface of the water, or underwater, if used in a submersible craft.","Although illustrative embodiments of the present disclosure have been described herein with reference to the accompanying drawings, it is to be understood that the disclosure is not limited to those precise embodiments, and that various other changes and modifications may be affected therein by one skilled in the art without departing from the scope or spirit of the disclosure.","The above description is that of current embodiments of the invention.","Various alterations and changes can be made without departing from the spirit and broader aspects of the invention as defined in the appended claims, which are to be interpreted in accordance with the principles of patent law including the doctrine of equivalents.","Any reference to elements in the singular, for example, using the articles “a,” “an,” “the,” or “said,” is not to be construed as limiting the element to the singular."]],"string":"[\n [\n \"INDUCTIVE VEHICLE\",\n \"An inductively powered toy vehicle and an associated track with inductive charging segment.\",\n \"The vehicle may include a secondary coil, a drive motor, an electrical power storage device connected between said secondary coil and said drive motor, and a wireless communications unit.\",\n \"The charging segment may include a primary coil, a sense circuit operable to detect the presence of the vehicle based on a change in the detected impedance of the primary coil, and a power control unit operable to provide a time-varying current to the primary coil when the vehicle traverses the charging segment.\",\n \"The primary coil is positioned within the race track adjacent the track upper surface.\",\n \"The vehicle drive motor may be operable at first and second speed settings, and a remote control device can provide operating instructions to the vehicle wireless communications unit.\"\n ],\n [\n \"1.A vehicle for traversing a charging circuitry having a primary coil configured to generate an inductive field, said vehicle comprising: a secondary coil; and a load electrically connected to said secondary coil; wherein said load receives electrical power from said secondary coil; wherein said vehicle is configured to perform an automated vehicle control action for a pre-set period of time based on a signal associated with the charging circuitry when proximate the charging circuitry.\",\n \"2.The vehicle of claim 1 wherein said load includes an energy storage device, the vehicle further including a charge condition indicator to provide an indication based on the available charge remaining in said energy storage device.\",\n \"3.The vehicle of claim 1 wherein said load includes a drive motor and an electrical power storage device electrically connected to said drive motor.\",\n \"4.The vehicle of claim 3 wherein said drive motor is operable at a plurality of speed settings based on the signal associated with said charging circuitry.\",\n \"5.The vehicle of claim 4 wherein said vehicle includes a sensor to detect said signal associated with said charging circuitry, said sensor being one of an electromagnetic sensor, a mechanical sensor, and an optical sensor.\",\n \"6.The vehicle of claim 5 further including a microcontroller to regulate an operating parameter of said vehicle, said operating parameter including at least one of vehicle speed and vehicle steering.\",\n \"7.A vehicle capable of traveling proximate an inductive charging station, said vehicle comprising: a controller; a secondary coil; and an electrical power storage device electrically connected to said secondary coil; wherein said controller is configured to initiate an automated vehicle control action based on a signal associated with the inductive power station, such that said vehicle performs said automated vehicle control action when proximate said inductive power station and such that said vehicle performs said automated vehicle control action for a pre-set period of time.\",\n \"8.The vehicle of claim 7 including a display unit to provide an indication of a charge level remaining in said electrical energy storage device.\",\n \"9.The vehicle of claim 7 including a drive motor electrically coupled to said electrical power storage device.\",\n \"10.The vehicle of claim 9 wherein said vehicle is configured to deactivate said drive motor when said vehicle is proximate said inductive power station.\",\n \"11.The vehicle of claim 7 wherein said automated vehicle control action includes changing the speed of said vehicle.\",\n \"12.The vehicle of claim 7 including an RF circuit to receive the signal associated with said inductive power station, said RF circuit being separate from said secondary coil.\",\n \"13.A vehicle for traversing a charging circuitry having a primary coil configured to generate an inductive field, said vehicle comprising: a secondary coil; a load electrically connected to said secondary coil; a sensor configured to sense a signal associated with the charging circuitry; a controller in electrical communication with said load, said controller configured to detect the charging circuitry based on the signal associated with the charging circuitry, and said controller configured to perform an automated vehicle control action for a pre-set period of time in response to said controller detecting the charging circuitry.\",\n \"14.The vehicle of claim 13 wherein said sensor includes said secondary coil.\",\n \"15.The vehicle of claim 13 wherein said sensor includes an RF circuit to receive the signal associated with said charging circuitry, said RF circuit being separate from said secondary coil.\",\n \"16.The vehicle of claim 13 wherein said sensor includes one of an electromagnetic sensor, a mechanical sensor, and an optical sensor.\",\n \"17.The vehicle of claim 13 wherein said automated vehicle control action includes changing speed of said vehicle.\",\n \"18.The vehicle of claim 13 wherein said load includes a drive motor and an electrical power storage device electrically connected to said drive motor.\",\n \"19.The vehicle of claim 18 wherein said drive motor is operable at a plurality of speed settings based on the signal associated with said charging circuitry.\",\n \"20.The vehicle of claim 13 wherein said controller is configured to regulate an operating parameter of said vehicle, said operating parameter including at least one of vehicle speed and vehicle steering.\"\n ],\n [\n \" BACKGROUND OF THE INVENTION The present invention relates to providing inductive power to toy vehicles.\",\n \"Electrically powered race track toys are known.\",\n \"Some are intended for use on a grooved track surface, and are known as slot cars.\",\n \"These toy vehicles or slot cars are designed for use on a segmented electrified track surface that is equipped with a slot, for accepting a guide pin attached to the car, and a pair of electrical contacts on either side of slot, also on the bottom of the car, for contacting matching wires embedded in the track to provide power to the car's electric motor.\",\n \"Other cars are slot-less, and are retained on the track segments by curbs or walls on either side.\",\n \"In the case of slot-less cars, most if not all of the track surface is equipped with electrical contacts to provide power to the car's electric motor.\",\n \"The toy cars are typically controlled by a hand-held controller, which is connected by wire to the power supplied to the track.\",\n \"By varying the electrical power, such as by a rheostat or digitally, the speed of the cars can be varied according to the user's discretion.\",\n \"In the case of slot cars, steering is generally unavailable, as the slot and pin layout precludes deviation from the slot contained in the track.\",\n \"In slot-less cars, some control may be available by varying the speed of the cars and by utilizing rudimentary steering inputs.\",\n \"These toy cars, either slotted or slot-less, obtain electrical power required for motion from the track surface.\",\n \"Thus, good electrical conductivity and physical contact is required throughout the entire track surface, or the cars may stop or perform erratically.\",\n \"Consequently, the electrical contacts must normally be kept clean both on the track and on the cars.\",\n \"As the tracks are often placed in dusty areas, such as a floor surface, and electricity attracts lint and other particles, such as dust, users are often required to clean the track and the contacts of the cars for good performance.\",\n \"Another issue with the track segments involves the connection of the track segments to each other.\",\n \"As the track forms a circuit to conduct electricity from each track segment to the next, a strong connection between segments is normally required.\",\n \"The connection must normally provide considerable strength between adjacent track segments, but also remain easily detachable for track redesign or storage.\",\n \"Over time, these contact areas between track segments can become worn and the conductivity degraded.\",\n \"Additionally, the wires embedded in the track surface can oxidize while exposed to air, reducing the conductivity possible and reducing performance.\",\n \"The user will normally clean the wires with an eraser or contact cleaner to remove the oxidation.\",\n \"This is time-consuming and can be difficult, depending on the length of track to be cleaned.\",\n \"A race track toy that addresses the issues discussed above and provides for more flexibility and user enjoyment is desired.\"\n ],\n [\n \" SUMMARY OF THE INVENTION The aforementioned problems are overcome by the present invention wherein a vehicle toy system eliminates electrical contacts on both the vehicle and the track, replacing them with inductive elements.\",\n \"A wireless remote control allows users to operate the vehicle without an electrical connection.\",\n \"One embodiment of the toy vehicle system of the present disclosure includes a track with at least one inductive coil charging portion, one or more toy vehicles, each with inductive coil charging equipment, one or more wireless controllers for operating the toy vehicles, and a power supply that provides power to the at least one inductive coil charging track portion.\",\n \"Another embodiment of the present disclosure includes an inductive coil track portion that features a primary inductive coil in proximity to the track surface such that a vehicle coming into proximity of the surface receives an electrical charge.\",\n \"Yet another embodiment of the present disclosure includes a toy vehicle with an inductive secondary coil for receiving electrical power from an inductive coil-equipped track segment.\",\n \"Another embodiment of the present disclosure includes a toy vehicle with an inductive secondary coil for receiving electrical power from a source that is also connected to an electrical power storage device, such as a capacitor, a battery or the combination thereof.\",\n \"Another embodiment of the present invention includes an inductive primary coil track segment that detects the presence of a toy vehicle by inductively pinging for the presence of a secondary inductive coil, such as contained within a toy vehicle or remote control device.\",\n \"An embodiment of the present disclosure includes a toy vehicle with speed/throttle and/or steering controls broadcasting by a wireless control device to a receiver contained within the vehicle.\",\n \"An embodiment of the present disclosure includes a toy vehicle operable at first and second speed settings based on a detected signal associated with a track, the vehicle including an electromagnetic sensor, a mechanical sensor, or an optical sensor.\",\n \"An embodiment of the present disclosure includes a toy vehicle with steering operated by an electric relay device using wireless remote control.\",\n \"An embodiment of the present disclosure includes a toy vehicle or remote controller with power level or other performance indicators, such as light emitting diodes (LEDs) to display information such as charge level remaining.\",\n \"An embodiment of the present disclosure includes a toy vehicle with steering operated by an electric motor.\",\n \"An embodiment of the present disclosure includes a toy vehicle with computer controls for monitoring performance, training purposes, and providing entertainment variables.\",\n \"An embodiment of the present disclosure includes a track portion with a primary inductive coil.\",\n \"The track portion may include a sensor to detect the presence of a vehicle, and provide power to the vehicle's onboard secondary coil.\",\n \"Another embodiment of the present disclosure is a toy vehicle equipped with a secondary inductive coil, a primary inductive coil power station, and a remote control device for operating the toy vehicle.\",\n \"These and other objects, advantages, and features of the invention will be more fully understood and appreciated by reference to the description of the current embodiment and the drawings.\",\n \"It will be readily understood that the components of the present disclosure, as generally described and illustrated in the figures herein, may be arranged and designed in a wide variety of different configurations.\",\n \"Thus, the following more detailed description of the embodiments of the apparatus, system, and method of the present disclosure, as represented in accompanying figures, is not intended to limit the scope of the disclosure, as claimed, but is merely representative of selected embodiments of the disclosure.\",\n \"Reference throughout this specification to “one embodiment” or “an embodiment” (or similar) means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present disclosure.\",\n \"Thus, appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment.\",\n \"Furthermore, the described features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.\",\n \"In the following description, numerous specific details are provided, such as examples, to provide a thorough understanding of embodiments of the present disclosure.\",\n \"One skilled in the art will recognize, however, that the disclosure can be practiced without one or more of the specific details, or with other methods, components, materials, etc.\",\n \"In other instances, well-known structures, materials, or operations are not shown or described in detail in order to avoid obscuring aspects of the disclosure.\",\n \"The illustrated embodiments of the disclosure will be best understood by reference to the drawings, wherein like parts are designated by like numerals or other labels throughout.\",\n \"The following description is intended only by way of example, and simply illustrates certain selected embodiments of devices, systems, and processes that are consistent with the disclosure as claimed herein.\"\n ],\n [\n \"CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of U.S. Nonprovisional application Ser.\",\n \"No.\",\n \"14/023,730, entitled “INDUCTIVE SYSTEMS FOR VEHICLES”, filed Sep. 11, 2013, which is a continuation of U.S. Nonprovisional application Ser.\",\n \"No.\",\n \"12/622,465, entitled “INDUCTIVE TOY VEHICLE”, filed Nov. 20, 2009 (now U.S. Pat.\",\n \"No.\",\n \"8,545,284), which claims the benefit of U.S.\",\n \"Provisional Application No.\",\n \"61/116,908, filed Nov. 21, 2008, entitled “INDUCTIVE TOY VEHICLE.” BACKGROUND OF THE INVENTION The present invention relates to providing inductive power to toy vehicles.\",\n \"Electrically powered race track toys are known.\",\n \"Some are intended for use on a grooved track surface, and are known as slot cars.\",\n \"These toy vehicles or slot cars are designed for use on a segmented electrified track surface that is equipped with a slot, for accepting a guide pin attached to the car, and a pair of electrical contacts on either side of slot, also on the bottom of the car, for contacting matching wires embedded in the track to provide power to the car's electric motor.\",\n \"Other cars are slot-less, and are retained on the track segments by curbs or walls on either side.\",\n \"In the case of slot-less cars, most if not all of the track surface is equipped with electrical contacts to provide power to the car's electric motor.\",\n \"The toy cars are typically controlled by a hand-held controller, which is connected by wire to the power supplied to the track.\",\n \"By varying the electrical power, such as by a rheostat or digitally, the speed of the cars can be varied according to the user's discretion.\",\n \"In the case of slot cars, steering is generally unavailable, as the slot and pin layout precludes deviation from the slot contained in the track.\",\n \"In slot-less cars, some control may be available by varying the speed of the cars and by utilizing rudimentary steering inputs.\",\n \"These toy cars, either slotted or slot-less, obtain electrical power required for motion from the track surface.\",\n \"Thus, good electrical conductivity and physical contact is required throughout the entire track surface, or the cars may stop or perform erratically.\",\n \"Consequently, the electrical contacts must normally be kept clean both on the track and on the cars.\",\n \"As the tracks are often placed in dusty areas, such as a floor surface, and electricity attracts lint and other particles, such as dust, users are often required to clean the track and the contacts of the cars for good performance.\",\n \"Another issue with the track segments involves the connection of the track segments to each other.\",\n \"As the track forms a circuit to conduct electricity from each track segment to the next, a strong connection between segments is normally required.\",\n \"The connection must normally provide considerable strength between adjacent track segments, but also remain easily detachable for track redesign or storage.\",\n \"Over time, these contact areas between track segments can become worn and the conductivity degraded.\",\n \"Additionally, the wires embedded in the track surface can oxidize while exposed to air, reducing the conductivity possible and reducing performance.\",\n \"The user will normally clean the wires with an eraser or contact cleaner to remove the oxidation.\",\n \"This is time-consuming and can be difficult, depending on the length of track to be cleaned.\",\n \"A race track toy that addresses the issues discussed above and provides for more flexibility and user enjoyment is desired.\",\n \"SUMMARY OF THE INVENTION The aforementioned problems are overcome by the present invention wherein a vehicle toy system eliminates electrical contacts on both the vehicle and the track, replacing them with inductive elements.\",\n \"A wireless remote control allows users to operate the vehicle without an electrical connection.\",\n \"One embodiment of the toy vehicle system of the present disclosure includes a track with at least one inductive coil charging portion, one or more toy vehicles, each with inductive coil charging equipment, one or more wireless controllers for operating the toy vehicles, and a power supply that provides power to the at least one inductive coil charging track portion.\",\n \"Another embodiment of the present disclosure includes an inductive coil track portion that features a primary inductive coil in proximity to the track surface such that a vehicle coming into proximity of the surface receives an electrical charge.\",\n \"Yet another embodiment of the present disclosure includes a toy vehicle with an inductive secondary coil for receiving electrical power from an inductive coil-equipped track segment.\",\n \"Another embodiment of the present disclosure includes a toy vehicle with an inductive secondary coil for receiving electrical power from a source that is also connected to an electrical power storage device, such as a capacitor, a battery or the combination thereof.\",\n \"Another embodiment of the present invention includes an inductive primary coil track segment that detects the presence of a toy vehicle by inductively pinging for the presence of a secondary inductive coil, such as contained within a toy vehicle or remote control device.\",\n \"An embodiment of the present disclosure includes a toy vehicle with speed/throttle and/or steering controls broadcasting by a wireless control device to a receiver contained within the vehicle.\",\n \"An embodiment of the present disclosure includes a toy vehicle operable at first and second speed settings based on a detected signal associated with a track, the vehicle including an electromagnetic sensor, a mechanical sensor, or an optical sensor.\",\n \"An embodiment of the present disclosure includes a toy vehicle with steering operated by an electric relay device using wireless remote control.\",\n \"An embodiment of the present disclosure includes a toy vehicle or remote controller with power level or other performance indicators, such as light emitting diodes (LEDs) to display information such as charge level remaining.\",\n \"An embodiment of the present disclosure includes a toy vehicle with steering operated by an electric motor.\",\n \"An embodiment of the present disclosure includes a toy vehicle with computer controls for monitoring performance, training purposes, and providing entertainment variables.\",\n \"An embodiment of the present disclosure includes a track portion with a primary inductive coil.\",\n \"The track portion may include a sensor to detect the presence of a vehicle, and provide power to the vehicle's onboard secondary coil.\",\n \"Another embodiment of the present disclosure is a toy vehicle equipped with a secondary inductive coil, a primary inductive coil power station, and a remote control device for operating the toy vehicle.\",\n \"These and other objects, advantages, and features of the invention will be more fully understood and appreciated by reference to the description of the current embodiment and the drawings.\",\n \"It will be readily understood that the components of the present disclosure, as generally described and illustrated in the figures herein, may be arranged and designed in a wide variety of different configurations.\",\n \"Thus, the following more detailed description of the embodiments of the apparatus, system, and method of the present disclosure, as represented in accompanying figures, is not intended to limit the scope of the disclosure, as claimed, but is merely representative of selected embodiments of the disclosure.\",\n \"Reference throughout this specification to “one embodiment” or “an embodiment” (or similar) means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the present disclosure.\",\n \"Thus, appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment.\",\n \"Furthermore, the described features, structures, or characteristics may be combined in any suitable manner in one or more embodiments.\",\n \"In the following description, numerous specific details are provided, such as examples, to provide a thorough understanding of embodiments of the present disclosure.\",\n \"One skilled in the art will recognize, however, that the disclosure can be practiced without one or more of the specific details, or with other methods, components, materials, etc.\",\n \"In other instances, well-known structures, materials, or operations are not shown or described in detail in order to avoid obscuring aspects of the disclosure.\",\n \"The illustrated embodiments of the disclosure will be best understood by reference to the drawings, wherein like parts are designated by like numerals or other labels throughout.\",\n \"The following description is intended only by way of example, and simply illustrates certain selected embodiments of devices, systems, and processes that are consistent with the disclosure as claimed herein.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS FIG.\",\n \"1 is a perspective view of a track and associated toy vehicle in accordance with an embodiment of the present invention.\",\n \"FIGS.\",\n \"2A-D disclose a race track toy according to at least one embodiment of the present disclosure.\",\n \"FIG.\",\n \"3 discloses a race track toy according to at least one embodiment of the present disclosure.\",\n \"FIGS.\",\n \"4A-D disclose a plurality of race track toy embodiments.\",\n \"FIGS.\",\n \"5A-B disclose a toy vehicle according to at least one embodiment of the present disclosure.\",\n \"FIG.\",\n \"6 discloses a toy vehicle in accordance with at least one embodiment of the present invention.\",\n \"FIG.\",\n \"7 discloses a plurality of toy vehicles and remote controls according to at least one embodiment of the present disclosure.\",\n \"FIG.\",\n \"8 discloses a toy vehicle with secondary inductive coil and controls, and a track segment with primary inductive coil and power supply control system, according to at least one embodiment of the present disclosure.\",\n \"FIG.\",\n \"9 discloses a circuit diagram for an inductive power track segment with inductive sense circuit according to at least one embodiment of the present disclosure.\",\n \"FIG.\",\n \"10 discloses a circuit diagram for an inductive power track segment with proximity detector according to at least one embodiment of the present disclosure.\",\n \"FIG.\",\n \"11 discloses a circuit diagram for the inductive power track section with sense circuit using infrared (IR) modulation according to at least one embodiment of the present disclosure.\",\n \"FIG.\",\n \"12 discloses a circuit diagram for the present disclosure including a sense circuit using a magnetic interaction and a Hall Effect sensor according to at least one embodiment of the present disclosure.\",\n \"FIG.\",\n \"13 discloses a circuit diagram for the sense circuit using inductive coupling to determine a toy vehicle position near the primary charging coil according to at least one embodiment of the present disclosure.\",\n \"FIG.\",\n \"14 discloses a process flow diagram for enabling and disabling the charging circuit.\",\n \"FIG.\",\n \"15 discloses a process flow diagram for charging a car or a remote control on a segment of track equipped with a primary inductive coil according to at least one embodiment of the present disclosure.\",\n \"FIG.\",\n \"16 discloses a sensor sequence using an inductive sensor to turn power on and off in a primary inductive coil track segment according to at least one embodiment of the present disclosure.\",\n \"FIG.\",\n \"17 discloses a sensor sequence using light, IR or magnetic sensors to turn power in the track segment primary coil according to at least one embodiment of the present disclosure.\",\n \"FIG.\",\n \"18 discloses a sensor sequence using light, IR, or magnetic sensors to turn power on or off in the track segment primary coil according to at least one embodiment of the present disclosure.\",\n \"FIG.\",\n \"19 discloses a diagram of the interoperability between the toy vehicle and the remote controller, whereby the energy storage in both are inductively charged according to at least one embodiment of the present disclosure.\",\n \"FIG.\",\n \"20 discloses a diagram for the charging and energy storage system inside the toy vehicle according to at least one embodiment of the present disclosure.\",\n \"FIG.\",\n \"21 discloses a circuit diagram for the charging and energy storage system inside the toy vehicle including a protection switch and a diode according to at least one embodiment of the present disclosure.\",\n \"FIG.\",\n \"22 discloses a circuit diagram showing AC mains power being transformed and rectified to provide DC power to the wireless power supply to at least one embodiment of the present disclosure.\",\n \"FIG.\",\n \"23 discloses a circuit diagram illustrating multiple track segments with primary inductive coils that are monitored by a drive controller according to at least one embodiment of the present disclosure.\",\n \"FIG.\",\n \"24 discloses a circuit diagram illustrating multiple track segments with primary inductive coils that are monitored by multiple drive controllers according to at least one embodiment of the present disclosure.\",\n \"FIG.\",\n \"25 discloses a circuit diagram illustrating AC mains power being transformed and rectified to power multiple segments of track containing primary inductive coils according to at least one embodiment of the present disclosure.\",\n \"FIG.\",\n \"26 discloses a circuit diagram illustrating radio frequency (RF) communication of an inductive coil equipped track segment according to at least one embodiment of the present disclosure.\",\n \"FIG.\",\n \"27 discloses a circuit diagram illustrating a discrete drive and steering control of a vehicle and a remote controller according to at least one embodiment of the present disclosure.\",\n \"FIG.\",\n \"28 discloses a circuit diagram illustrating a continuous (proportional) control of drive and steering control of a car and a remote controller according to at least one embodiment of the present disclosure.\",\n \"FIG.\",\n \"29 discloses a toy vehicle and start/finish line containing inductive coils according to at least one embodiment of the present disclosure.\",\n \"FIG.\",\n \"30 discloses a toy vehicle and pit stop/gas station containing inductive coils according to at least one embodiment of the present disclosure.\",\n \"FIG.\",\n \"31 discloses a toy train and railroad containing inductive coils according to at least one embodiment of the present disclosure.\",\n \"FIG.\",\n \"32 discloses a boat and dock/poolside containing inductive coils according to at least one embodiment of the present disclosure.\",\n \"FIG.\",\n \"33 discloses a toy helicopter and landing pad containing inductive coils according to at least one embodiment of the present disclosure.\",\n \"FIG.\",\n \"34 discloses a toy aircraft and runway containing inductive coils according to at least one embodiment of the present disclosure.\",\n \"DESCRIPTION OF THE CURRENT EMBODIMENT With reference to FIG.\",\n \"1, a toy vehicle system including an inductively powered toy vehicle 40, at least one track segment 42, and an associated control module 44 is shown.\",\n \"The vehicle 40 is drivable on a track including at least one segment 42 having a wireless power supply to generate an inductive field, wherein the vehicle 40 receives power from the inductive field when it traverses the track segment 42.Though shown as adapted for use on a circuit formed of multiple interconnected track segments 42, the toy vehicle 40 may also be used with only a single track segment 42 in combination with any suitable driving surface.\",\n \"With reference to FIGS.\",\n \"2A-2D, track segments 42 may be straight, curved, a combination of both, or other shapes, such as an intersection or a pit road track segment.\",\n \"Plastic or other formable material may be used to construct the track segments, which optionally include connectors (not shown) to join other track segments together.\",\n \"These connectors allow for a smooth transition surface or joint between the track segments so as to allow for the toy cars or vehicles to pass between sections unhindered.\",\n \"Additionally, the optional connectors also allow for users to quickly disconnect the track segments to make alterations to the track layout or assemble a new circuit.\",\n \"As shown in FIG.\",\n \"2B, the track segment 42 is curved in a constant radius, to allow the vehicles to make a ninety degree turn.\",\n \"Track segments 42 may be formed of any shape however, such as an intersection, sweeping curve, or other shape.\",\n \"Optional lateral barriers or guard rails 43 may be used to contain the toy vehicles on the track surface, since the toy vehicles can be steerable and guide pins are unnecessary.\",\n \"The guard rails 43 can help prevent vehicles from exiting the track segments 42, unless using specific segments equipped with exit ramps (not shown) where fences are omitted.\",\n \"The track segments 42 can be easily presented in a circuit format as shown in FIG.\",\n \"2C, where a number of straight and curved segments 42 or portions are arranged to form a circuit.\",\n \"Using the integrated connectors of the track segments 42, a complete circuit 45 is shown in FIG.\",\n \"1D, whereby vehicles may lap repeatedly without leaving the circuit 45 due to the guard rails 43.A track segment 42 with a primary inductive element 46 is shown in FIG.\",\n \"3.The primary inductive element 46 can be any conductive element operable to produce a magnetic field when subject to a time-varying current, including a coil, for example.\",\n \"A power and control unit 48 receives AC mains power from an external source (not shown), such as a wall outlet, and transforms and rectifies it to supply power to the track segment 42.At least one optional sensor 50, 52 is shown as a component to the track segment 42.The sensor 50, 52 can detect the presence of a vehicle entering and/or exiting the track segment 42.In one embodiment, a signal may be communicated from the sensor 50, 52 to the power and control unit 48 to power up the primary coil 46 if the sensor 50, 52 indicates that a vehicle is entering the track segment 42 and power down the primary coil 46 if a vehicle is leaving the segment 42.Additionally, the sensor 50, 52 may provide information for an optional race status display unit 54.The optional race status display unit 54 may display information such as the vehicle's lap speed and other performance parameters such as lap time, place, or other pertinent data.\",\n \"Optionally, the vehicle 40 may be uniquely identified using specific resonant signals or other electronic marking, such as digital technology, and the display unit 54 can determine which vehicle has entered the track segment 42, or if multiple vehicles 40 enter, their places can be accurately determined.\",\n \"The optional sensors 50, 52 may be embedded within the track surface 56, side rails 42, or attachable using a fastening method, such as snap-on or adhesive.\",\n \"In this way, additional sensors 50, 52 can be placed about the track 45 to measure performance in portions of a circuit, such as a racing training aid or performance meter.\",\n \"While one primary inductive coil 46 is shown in a track segment 42 in FIG.\",\n \"3, multiple primary coils may be included in a track segment 42 or other application suitable for coil shapes, such as a pad, start/finish line, or other suitable surface for engagement with a vehicle.\",\n \"For example, a plurality of primary coils arranged in a staggered pattern or an array of coils allows for power to be transferred to vehicles with secondary coils in a number of variations.\",\n \"FIGS.\",\n \"4A-D are illustrations of various race track arrangements.\",\n \"A primary inductive coil segment or charging portion 56 is shown as a part of a race track circuit 44.For illustrative purposes only, an oval is shown; however a circuit of any shape may be constructed.\",\n \"The primary inductive coil segment 56 is connected to a power, control, and race status unit 58 which provides mains power and optionally processes race car performance data from the sensors (not shown) included in the track segment(s) 56.In another embodiment as shown in FIG.\",\n \"4B, two primary inductive coil segments 56 are shown as a portion of a race track circuit 45.For both segments 56, power, control, and race status unit connections may be provided.\",\n \"In another embodiment as shown in FIG.\",\n \"4C, three primary inductive coil segments 56 are shown as a portion of a race track circuit 45, each may be provided with connection to the power, control, and race status unit 58.In yet another embodiment as shown in FIG.\",\n \"4D, four primary inductive coil segments 56 are shown as a portion of a race track circuit 45, each provided with connection to the power and race and control unit 58.By utilizing multiple primary coil track segments 56, the toy vehicle 40, for example a race car 60, may receive additional charging opportunities; data may be gathered about their performance in multiple sections of the track, as well as other performance or entertainment data.\",\n \"For example, one primary coil segment 56 could be located in a pit area, such that a vehicle 40 may pause and “refuel” by charging inductively.\",\n \"Additionally, the control unit may retain a vehicle 40 in a segment 42 by sending a signal to the vehicle to deactivate it for a period of time, such as to serve a penalty or “black flag”.\",\n \"Another feature of the present disclosure is the adaptability of the track segments 56 with inductive coils 46 to be equipped with adapters for use with other existing and future track circuits and vehicles, or as a stand-alone additional accessory for vehicles not requiring a track circuit.\",\n \"For example, an adapter attached to a track segment with inductive coils may be inserted into a track system, allowing for vehicles equipped with inductive secondary coils to use the track circuit.\",\n \"Further, the remote controllers may also receive charging from the inductive track segment 56 due to their own on-board secondary coils.\",\n \"FIGS.\",\n \"5A-B are illustrations of a race car 60 according to at least one embodiment of the disclosure.\",\n \"As shown in FIG.\",\n \"5A, the race car 60 can include a body shell 62 and chassis 64 with various components.\",\n \"FIG.\",\n \"5B shows the race car 60 with the body shell 62 removed, revealing the chassis 64 with various components.\",\n \"The drive motor 66 is shown, which is equipped with a gear that engages a second gear located on a drive shaft, connected to a pair of wheels.\",\n \"Note that in this embodiment, the rear wheels of the race car 60 are the drive wheels, but in other embodiments, the race car 60 may have front wheel drive or all-wheel drive.\",\n \"Additionally, other means of providing power to the wheels may be used, such as a belt drive system, or individual motors may be located at some or all of the wheels.\",\n \"On the bottom of the chassis 64 is the secondary inductive element 68, which selectively receives electrical power when in proximity to a track segment 42 containing a primary inductive coil 46.The secondary inductive element 68 can be any conducting element adapted to generate a current when subject to a time-varying magnetic field, including a secondary coil, for example.\",\n \"The energy storage system 70 is shown in the middle portion of the chassis 64 in this embodiment, but may be located elsewhere on the chassis 64.As the coil 68 is energized, electrical power is transferred to the energy storage system 70, which may include a battery, a capacitor, a combination of both, or another suitable energy storage device.\",\n \"A microcontroller 72 includes an RF receiver or other wireless communications device and is optionally located on the chassis 64.The microcontroller 72 receives signals from a control unit (not shown) which is operated by the user, by the track control unit, or by internal control circuitry, such as a pace car or training aid.\",\n \"The microcontroller 72 can regulate the race car speed, steering, and other control features, such as lights.\",\n \"In the current embodiment, the steering mechanism 74 includes a relay, servomotor, or other means for changing the front wheel direction so as to allow the user to steer the race car 60.Additionally, the rear or all wheels may also feature steering for additional performance.\",\n \"As shown in FIG.\",\n \"6, the secondary coil 68 can optionally extend beyond the length and width of the wheel base of the car 60, or circumferentially encompass the each of the four tractive wheels.\",\n \"This configuration can achieve an enhanced transfer of power, with the secondary coil 68 optionally functioning as a bumper for the car 60 during racing.\",\n \"FIG.\",\n \"7 illustrates a race car controller 76 and a race car 60.Additional race cars 78 may be controlled by additional controllers 80 with complimentary, non-interfering, independent wireless communication.\",\n \"A controller 76 is shown with a number of control options, such as speed setting, steering, and braking.\",\n \"Other, different, or fewer controls may also be included, such as a graphic display providing car data, light control, battery power remaining in the car and controller, as well as other features.\",\n \"A wireless link may be established between the controller 76 and race car 60.This link allows for the user to operate or drive the car 60 around a track circuit 45 or outside of a track circuit 45 if desired.\",\n \"The car 60 may be recharged by driving it onto or over a primary coil track segment 56 or other embodiment of a track segment, such as a pit stop or gas station (not shown).\",\n \"The wireless communication may be RF, infrared, Bluetooth, or some other wireless communication method.\",\n \"Optionally, the controller 76 may include variable speed control and continuous steering control instead of discrete steering inputs.\",\n \"FIG.\",\n \"8 is a cutaway view of a toy race car 60 including a secondary inductive coil 68 located on the car chassis 64, which receives energy and transfers it to storage device 70.The energy may be rectified in an optional rectify unit 82.A power control 84 and a microcontroller 86 receive energy from the storage device 70, which may be a battery, capacitor, combination of both or other suitable energy storage device.\",\n \"An RF communications circuit 88 receives energy from power control 84 and the microcontroller 86, and can receive and transmit wireless signals to the user controller (not shown) to operate the race car 60.A Drive and Speed FWD/REV unit 90 is shown, which in this embodiment is the rear drive wheels, including an electric motor and gear system.\",\n \"Steering control 92 is shown at the front of the race car 60, which receives signals from the microcontroller 86, which in turn receives signal commands from the user remote control (not shown) as to which direction the user desires the race car to move.\",\n \"An ID unit 94 is shown within the race car 60, which includes unique car information that may be transmitted to the race track power and race control unit (not shown).\",\n \"Such ID information could include type of vehicle, performance level, driver ID, or other information.\",\n \"The drive motor 66 can be operated at multiple speed settings based on a detected signal associated with a portion of the track 45.For example, a first speed setting could be set by the vehicle microcontroller 86 to prevent the drive motor 66 from draining the energy storage device 70 to quickly.\",\n \"A second speed setting could be set by the microcontroller 86 to provide increased vehicle speed during short intervals in which increased vehicle speed is desired, e.g., in a run-up to a ramp or loop.\",\n \"The microcontroller 86 can switch between speed settings in response to a signal associated with a portion of the track 45, for example, an inductively powered track segment 56.Upon receiving the signal, optionally through the secondary coil 68 or the RF circuit 88, the microcontroller 86 could control the drive motor to increase or decrease the power drawn from the storage device 70.The change in drive motor control could be momentary (i.e., pre-set for a period of time) or permanent (i.e., continuing until a second signal is detected during the course of the vehicle's movement about the track).\",\n \"As discussed in greater detail below, the signal can also be generated by a magnet in combination with a Hall Effect sensor, an LED in combination with a photodiode, or a mechanical switch in combination with an actuator, for example.\",\n \"As also shown in FIG.\",\n \"8, a wireless power supply 106 including a primary inductive coil 46 is shown embedded in a track segment 42.An inverter 96 is shown connected to the primary coil 46, as well as a microcontroller 98, which, in the current embodiment, receives signals from the sense circuit 100 to activate when the race car 60 is in proximity to the track segment 42.A DC/DC converter 102 is connected to the inverter 96 and microcontroller 98 and receives power from a DC input 104.As shown in FIG.\",\n \"9, the sense circuit 100 can be an inductive sense circuit 108.Power is supplied by mains input 110, which is then rectified by mains rectifier 112.The inductive sense circuit 108 monitors the impedance of the primary coil 46 and generates a signal which is analyzed by the control unit 114 to determine if a vehicle 40, for example a race car 60, is in the proximity of the primary coil 46.The inductive sense circuit 108 may also determine the identity of the race car 60 and monitor performance.\",\n \"The performance information can also be used to monitor lap counts and race status, for example.\",\n \"Rectified power is sent through the DC/DC converter 116 and the inverter 118 which energizes the inductive coil 68 if a race car 60 is in proximity.\",\n \"In another embodiment as shown in FIG.\",\n \"10, the sense circuit 100 can be a vehicle proximity sense circuit or proximity detector 120.By using a proximity detector 120, energy is conserved by only energizing the primary coil 46 within the track segment 42 when a race car 60 is in proximity, e.g., when the race car 60 traverses the track segment 42.Additionally, the activating of the proximity detector 120 may be used to record laps or other performance data due to the unique identification of each vehicle.\",\n \"Power is supplied by mains input 110, which is then rectified by the mains rectifier 112.The proximity detector 120 determines if a vehicle is in proximity and generates a signal which is analyzed by the control unit 114.Rectified power is sent through the DC/DC converter 116 and the inverter 118 which energizes the primary inductive coil 46 if a vehicle is in proximity.\",\n \"FIG.\",\n \"11 is a block diagram of one embodiment of a sense circuit 100 using IR or wireless modulation, such as shown in FIG.\",\n \"8.An IR or other wireless transmitter 122 is located on a race car 60, which transmits a signal to the sense circuit 100.An IR or wireless sensor and demodulator 124 receives the signal, which is amplified by amplifier 126 before being sent to signal conditioner 128, which sends an output signal to the control unit (not shown) and receives power from the rectifier (not shown).\",\n \"Each race car 60 may be equipped with an IR transmitter or other wireless transmitter 122 which emits an encoded unique signal which is detected when the car 60 is present near the sense circuit 100, such as may be located in a primary inductive coil track segment 56.Information encoded on the transmitted signal is used to identify the car, its performance, or other information.\",\n \"Additionally, optical sensors such as photoelectric eyes may also be used.\",\n \"FIG.\",\n \"12 is a block diagram of one embodiment of a Hall Effect proximity sense circuit 100 such as shown in FIG.\",\n \"8.A magnet 130 is located on each race car 60.The Hall Effect sensor 132 differentiates between particular cars based on the unique magnetic signal of each magnet 130 onboard each car.\",\n \"An arrangement of different sizes and polar orientations of the magnets 130 allows for multitudes of combinations for car identification.\",\n \"The signal generated by the Hall Effect sensor 132 enters the amplifier 126 before being passed to the signal conditioner 128, which outputs the signal to the control unit (not shown) and receives power from the rectifier (not shown).\",\n \"FIG.\",\n \"13 is a block diagram of an inductive sense circuit 108 showing a race car 60 or remote control 76, either of which being equipped with a secondary inductive coil 68 in proximity to the primary coil 46.The primary coil 46 may be located in a track segment 42 or other suitable location, such as a charging station or holster, or a pit garage location.\",\n \"The inductive sensor and signal generator 134 detects the presence of a load 68 in proximity to the primary coil 46, optionally based on a change the detected impedance of the primary coil when the car 60 is proximate the inductive track segment 56, and sends a signal to the amplifier 126, which then passes the amplified signal to the signal conditioner 128 for output to the control unit (not shown) as the sense circuit 108 continues to receive power from the rectifier (not shown).\",\n \"FIG.\",\n \"14 illustrates a process flow diagram describing one embodiment of a race car or remote charge sequence.\",\n \"The primary coil 46 with sensor unit 100, such as enclosed within a track section 42, determines whether a car 60 is present, using a motion sensor 120 or inductive sense circuit 108.If no car is present, the primary coil 46 remains de-energized.\",\n \"If a car or remote is present, however, the control unit is powered up, which using sensors determines the car identity, speed, and other data, and transmits the data to the power and race control unit 58.Power is then applied to the primary coil 46 for the period the car 60 is present.\",\n \"Once the race car 60 has passed out of the presence of the primary coil 46, or a foreign object is detected, the primary coil 46 is de-energized until another race car 60 enters the proximity of the primary coil 46.Accordingly, the primary coil 46 provides wireless power to the car 60 in increments corresponding to successive traversals of the inductive charging segment 56 by the race car.\",\n \"FIG.\",\n \"15 is a process flow diagram describing another embodiment of a race car or remote charge sequence.\",\n \"The primary coil 46 with sensor unit 100, such as enclosed within a track section 42, determines whether a car 60 or remote control is present, using a motion sensor 120 or inductive sense circuit 108.If no car 60 or remote 76 is present, the primary coil 46 remains de-energized.\",\n \"If a car 60 or remote 76 is present, however, the control unit 114 is powered up, which using sensors determines the car identity, speed, and other data, and transmits the data to the power and race control unit 58.Power is then applied to the primary coil 46 for the period the car 60 or remote 76 is present.\",\n \"Once the race car 60 has passed out of the presence of the primary coil 46, the remote 76 is removed, or a foreign object is detected, the primary coil 46 is de-energized until another race car 60 or remote 76 enters the proximity of the primary coil 46, or until the foreign object is removed.\",\n \"Accordingly, the primary coil 46 provides wireless power to the car 60 in increments corresponding to successive traversals of the inductive charging segment 56 by the race car.\",\n \"FIG.\",\n \"16 is a graph of one embodiment of a sensor sequence using an inductive sensor to energize and de-energize a primary inductor coil.\",\n \"In section A, the inductive sensor 134 periodically checks for the presence of a race car 60.As the car 60 enters the range of the sensor 134, the inductive sensor 134 detects the presence of a load 68 and activates the primary coil 46, energizing it to provide power to the race car 60.Once the race car 60 has passed out of the range of the inductive sensor 134, the primary coil 46 is deactivated and the inductive sensor 134 returns to a periodic checking mode, until the next race car 60 enters the range of the inductive sensor 134.FIG.\",\n \"17 is a graph of one embodiment of a sensor sequence with using various sensing techniques, including light, IR, magnetic sensors, or other wireless communication.\",\n \"As a race car approaches a sensor, it is wirelessly detected, and the sensor signal is communicated to the control unit which energizes the primary coil located in a track segment, for example.\",\n \"The sensor continues to detect the presence of the car, and maintains the signal sent to the control unit.\",\n \"FIG.\",\n \"18 is a graph of one embodiment of a sensor sequence with using various sensing techniques, including light, IR, magnetic sensors, or other wireless communication.\",\n \"As a race car approaches a sensor, it is wirelessly detected, and the sensor signal is communicated to the control unit which energizes the primary coil located in a track segment, for example.\",\n \"The sensor continues to detect the presence of the car, and maintains the signal sent to the control unit.\",\n \"After a period of time, the car departs the range of the sensor, and primary coil is de-energized.\",\n \"FIG.\",\n \"19 is a block diagram illustrating the interoperability of an inductive wireless power supply 106, a toy vehicle 40, and a vehicle controller 76.As described above in connection with FIG.\",\n \"14, the wireless power supply 106 can include a DC/DC converter 116 connected to an inverter 118 and microcontroller 98 and receives power from a DC input 104.The wireless power supply 106 is shown as including an inductive sense circuit 108, but can also include a proximity detector 120 as explained above in connection with FIG.\",\n \"10.The toy vehicle 40 and remote control 76 can each include an inductive secondary 68, a rectify and charge control circuit 85 as described above in connection with FIG.\",\n \"9, and a vehicle energy storage unit 70.In operation, the wireless power supply 106 provides a varying magnetic field to induce an alternating current in the respective secondary coils 68 of the toy vehicle 40 and remote control 76.Once rectified by the rectifier and charge control circuit 85, current supplied by the secondary coil can be stored in the energy storage unit 70.As shown in FIG.\",\n \"20, the vehicle energy storage device can include a charge control unit 136, a storage device 138 and a protection/regulation device 140.The storage device 138 can include a battery, capacitor, combination of both, or other storage device.\",\n \"The voltage is conditioned to the appropriate values for the subsequent circuit elements in the protection/regulation device 140.Output signals are produced by the protection/regulation device 140 which indicate the charge state of storage device 138 and are sent to the car control unit (not shown).\",\n \"As shown in FIG.\",\n \"21, the vehicle energy storage unit 70 includes a protection switch 142 and diode 144 after the voltage input point.\",\n \"The switch 142 allows for the isolation of the energy storage circuit 70 if so desired and the diode 144 constrains flow only into the charge control circuit block.\",\n \"FIG.\",\n \"22 is one embodiment of a circuit diagram of AC mains power being transformed and rectified in the DC power supply 146, which using a cable 148, can be remotely located from the wireless race track power supply 106, allowing for large track circuits and freedom from mains power outlet locations.\",\n \"FIG.\",\n \"23 is one embodiment of a circuit diagram illustrating multiple inductive track segments 56 being monitored, powered and controlled by a single drive controller 114.Mains voltage 110 is supplied to the wireless power supply 106.As the voltage enters the power supply, it first passes to the rectifier 112, after which the sense circuit 100 monitors the presence of race cars (or other secondary coil-equipped devices) at multiple track segments.\",\n \"A single drive control unit 114 is connected to the multiple track segments, each with its own primary coil 46.As race cars enter the proximity of the various coils, the sense circuit detects their load and allows for power to the supplied to the particular coil where a car is present, for the period that the car is present.\",\n \"FIG.\",\n \"24 is a circuit diagram illustrating multiple inductive track segments 56 being monitored, powered and controlled by multiple drive controllers 114.Mains voltage 110 is supplied to the wireless power supply 106.As the power enters the power supply, it first passes to the rectifier 112, after which the sense circuit 100 monitors the presence of race cars (or other secondary coil-equipped devices) at multiple track segments.\",\n \"Multiple drive control units 114 are connected to the multiple track segments, each with its own primary coil 46.As race cars enter the proximity of the various coils, the sense circuit detects their load and allows for power to the supplied to the particular coil where a car is present, for the period that the car is present.\",\n \"FIG.\",\n \"25 is a circuit diagram illustrating mains power being transformed and rectified to power multiple inductive track segments, including the separation of the mains rectification and the DC/DC conversion from the remainder of the race track using a cable.\",\n \"Mains voltage is supplied to the DC power supply 146, containing a rectifier and a DC/DC converter.\",\n \"Connected to the DC power supply is cable 148, which allows for separation of the DC power supply and the wireless power supply 106, which includes an internal power supply 150, connected to a sense and sense control unit 100, which monitors the presence of race cars (or other secondary coil-equipped devices) at multiple track segments.\",\n \"Multiple drive control units 114 are connected to the multiple track segments, each with its own primary coil 46.As the voltage enters the power supply, it first passes to the rectifier 112, after which the sense circuit 100 monitors the presence of race cars (or other secondary coil-equipped devices) at multiple track segments.\",\n \"Multiple drive control units 114 are connected to the multiple track segments, each with its own primary coil 46.As race cars enter the proximity of the various coils, the sense circuit detects their load and allows for power to the supplied to the particular coil where a car is present, for the period that the car is present.\",\n \"FIG.\",\n \"26 is a circuit diagram illustrating one embodiment of RF remote communication of the inductive segments of race track, which allows for wireless control of the power supply and communication between the components.\",\n \"A remote control unit 76 includes an input and control interface 153, a stored power device 70, such as a battery, and a RF or wireless circuit 152, which is connected to an optional antenna 154.The remote control unit 76 communicates with the wireless power supply 106 using RF, infrared, Bluetooth or other type of wireless communication.\",\n \"Mains power is supplied to the wireless power supply.\",\n \"There, mains power is supplied to the RF/wireless communications circuit 156, though DC power may also be used.\",\n \"Mains power is rectified by the rectifier 112, after which the output is monitored by the power supply control unit 114 and the sense circuit 100, which also is connected to the RF communications circuit.\",\n \"The DC/DC converter processes the rectified power and sends it to the inverter 118, after which the power is sent to the primary coil 46, which is located in a track segment 42 or other suitable location.\",\n \"The remote control 76, toy vehicle 40, or inductive track segment 56 can include a charge condition indicator (not shown) to provide an indication based on the available charge remaining in a storage device 70 in either of the remote control 76 or toy vehicle 40.FIG.\",\n \"27 discloses a circuit diagram illustrating a discrete drive and steering control of a car and a remote controller 76.Within the controller is a RF transmit and receive circuit 152, connected to an input and control interface 153, which features operational controls, such as forward/reverse, turn right/left, and other vehicle controls.\",\n \"The remote controller 76 is powered by a stored power device 70, which may be a battery, a capacitor, a combination of both, or another suitable power storage device.\",\n \"The remote controller 76 also includes an antenna 154, which may be external or internal.\",\n \"The car drive control circuit 170 is located within a vehicle (not shown) and includes a charge storage device, which may be a battery, a capacitor, a combination of both, or another suitable power storage device.\",\n \"The charge storage device 156 is connected to a DC/DC converter 160, which provides power to the RF transmit and receive circuit 158.Signals from the circuit 158 are relayed to the microcontroller 86, which also is powered by the DC/DC converter 160.The microcontroller controls the steering control voltage unit 162 and the wheel drive voltage unit 164.The drive motor 168 receives regulated voltage from the wheel drive voltage unit resulting in varying vehicle speed according to user input on the remote controller 76.The steering solenoid 166 receives regulated voltage from the steering control voltage unit 162 resulting in varying vehicle direction according to user input on the remote controller 76.As noted above in connection with FIG.\",\n \"26, the remote control 76, toy vehicle 40, or inductive track segment 56 can include a charge condition indicator (not shown) to provide an indication based on the available charge remaining in a storage device 70 in either of the remote control 76 or toy vehicle 40.FIG.\",\n \"28 discloses a circuit diagram illustrating a continuous (proportional) control of drive and steering control of a car 60 and a remote controller 76.Within the controller is a RF transmit and receive circuit 152, connected an input and control interface 153, which features operational controls, such as forward/reverse, turn right/left, and other vehicle controls.\",\n \"The remote controller is powered by a stored power device 70, which may be a battery, a capacitor, a combination of both, or another suitable power storage device.\",\n \"The remote controller 76 also includes an antenna 154, which may be external or internal.\",\n \"The car drive control circuit 170 is located within a vehicle (not shown) and includes a charge storage device, which may be a battery, a capacitor, a combination of both, or another suitable power storage device.\",\n \"The charge storage device is connected to a DC/DC converter 160, which provides power to the RF transmit and receive circuit 158.Signals from the circuit 158 are relayed to the microcontroller 86, which also is powered by the DC/DC converter.\",\n \"The microcontroller controls the proportional steering control voltage unit 172 and the proportional wheel drive voltage unit 174.The drive motor 168 receives regulated voltage from the wheel drive voltage unit resulting in varying vehicle speed according to user input on the remote controller 76.The steering solenoid 166 receives regulated voltage from the proportional steering control voltage unit 172 resulting in varying vehicle direction according to user input on the remote controller 76.FIG.\",\n \"29 discloses one embodiment of an inductive charging segment 56 including start/finish line 200 with a power supply 202 and a primary inductive coil (not shown) located within the start/finish line.\",\n \"A car 60 containing a secondary inductive coil 68 and control system (not shown) is controlled by a wireless remote controller (not shown), also containing a secondary coil, operated by a user.\",\n \"As the user drives the car 60 across the start/finish line 200, a charge is received by the vehicle's secondary coil 68 and is stored by the vehicle's onboard storage device.\",\n \"This charge allows for the vehicle to continue operating.\",\n \"For example, a user can position the start/finish line 200 in an area and create a custom race circuit, or simply place the start/finish line 200 in an area that the user decides to operate the vehicle.\",\n \"A display (not shown) contained on the start/finish line 200 and/or the vehicle 60 and its controller provide the user with charge level information.\",\n \"Optionally, the charging segment 56 can include one or more ramps or inclines 203 extending from the lateral edges of the charging segment 56 to permit a car 60 to drive onto and off of the charging segment 56.FIG.\",\n \"30 discloses a charging segment 56 including a charge station or pit stop 204 with a power supply 202 and a primary inductive coil (not shown) located within the pit stop 204.A car 60 containing a secondary inductive coil 68 and control system (not shown) is controlled by a wireless remote controller (not shown), also containing a secondary coil, operated by a user.\",\n \"As the user drives the car 60 across the pit stop 204, a charge is received by the vehicle's secondary coil 68 and is stored by the vehicle's onboard storage device.\",\n \"This charge allows for the car 60 to continue operating.\",\n \"For example, a user can position the pit stop 204 in an area and create a custom race circuit, or simply place the pit stop in an area that the user decides to operate the car 60.A display (not shown) contained on the pit stop 204 and/or the car 60 and its controller provide the user with charge level information.\",\n \"A suitable decoration such as a gas pump 206 may be used to identify the charging location.\",\n \"Optionally, the charging segment 56 can include one or more ramps or inclines 203 extending from the lateral edges of the charging segment 56 to permit a car 60 to drive onto and off of the charging segment 56.Though described above in connection with a race car moveable along a toy race track, the present invention can also be incorporated in other toy vehicles, including a toy train 192, a toy boat 194, a toy helicopter 196, or toy airplane 198, for example.\",\n \"As shown in FIG.\",\n \"31, the present invention can include a train 192 moveable along a railroad track 176 equipped with a primary inductive coil 46.Onboard the train is a wireless control unit 170 according to the present disclosure, and powering the railroad track primary coil is a power and control unit according to the present disclosure.\",\n \"As the user controls the train 192, it moves over the inductive coil 46 incorporated into the railroad track section.\",\n \"In doing so, a charge is received by the secondary coil 68 onboard the train 192, which is stored in a suitable storage device.\",\n \"The train's electric motor then powers the train about the railroad circuit, and receives another charge when it passes over the primary coil equipped track segment again.\",\n \"In this embodiment, a train engine, railroad car, trolley, or other rolling stock may be equipped with secondary coils, energy storage devices, and other controls which may be wirelessly controlled by the user, or automatic in operation.\",\n \"Additionally, as disclosed above, a wireless remote control device equipped with a secondary coil and energy storage device is used to control the train, though a traditional power supply may also be used, to send digital signals through the track while power is supplied by inductive coil.\",\n \"In another embodiment, the primary inductive coil 46 may be incorporated in other railroad accoutrements, such as buildings, landscaping or the rail bed.\",\n \"Locating inductive coils about a train layout provides power to buildings, street lights, and other decorations without traditional wiring.\",\n \"As shown in FIG.\",\n \"32, the inductively powered vehicle can include a motorized boat 194 having a secondary coil 68 and control system 170 as disclosed above.\",\n \"The boat 194 can be controlled by a wireless remote controller 76 including a secondary coil 68, and the primary inductive coil 46 and associated power supply system circuitry 106 can be incorporated into a portion of a dock or a portion of a poolside 178, for example.\",\n \"As a user operates the boat 194 via the remote controller 76, the boat 194 and/or controller 76 can include a charge condition indicator (not shown) to display the charge level remaining in the boat's onboard energy storage device and control system (not shown) as disclosed above.\",\n \"The display can allow a user to determine when to approach the primary coil equipped portion of the dock or pool side 178.The user can move the boat 194 from that location when the vessel is fully charged, or leave early if desired.\",\n \"In order to maintain a proximity to the primary coil equipped portion 178, a magnet 180 or other restraining device may be used, which may be positioned to prevent the boat 40 from departing until a full charge is received, for example.\",\n \"FIG.\",\n \"33 discloses a helicopter 196 with a secondary inductive coil 68 and control system 170 as disclosed above.\",\n \"The helicopter 196 is controlled by a wireless remote controller (not shown), also with a secondary inductive coil.\",\n \"A primary inductive coil 46 and power supply system is incorporated into a landing pad 182 or other suitable object.\",\n \"A user flies the helicopter 196 using the remote controller, and lands it on the landing pad 182 to receive a charge.\",\n \"The controller and/or helicopter 196 provide the user with charge level status.\",\n \"When the user desires, and the helicopter has sufficient charge, it may lift off and resume flight at the user's discretion.\",\n \"The primary coil 46 may be located in other objects aside from a landing pad, such as a target incorporated into a flying game.\",\n \"FIG.\",\n \"34 discloses an airplane 198 with a secondary inductive coil 68 and control system as disclosed above.\",\n \"The aircraft 40 is controlled by a wireless remote controller, also with a secondary inductive coil (not shown).\",\n \"A primary inductive coil 46 and power supply system is incorporated into a runway 184 or other suitable object.\",\n \"The user flies the airplane 198 using the controller and lands on the runway 184 for a charge.\",\n \"The controller and/or aircraft 198 provide the user with charge level status.\",\n \"When the user desires, and the aircraft 198 has sufficient charge, it may lift off and resume flight at the user's discretion.\",\n \"The primary coil 46 may be incorporated into other aviation-related objects, such as a taxiway or aircraft carrier.\",\n \"Accordingly, additional vehicles may utilize the inductive charging technology as detailed above.\",\n \"For example, toy aircraft such as helicopters or airplanes may be equipped with inductive coils and energy storage devices, along with control systems.\",\n \"A landing pad or runway may also be equipped with a primary inductive coil and power supply, enabling a user to land a craft on such a surface, similar to the track segments as in the race track, and receive a charge for the onboard storage energy storage device.\",\n \"The user can then command the craft to takeoff, using a wireless remote control, and enjoy another electrically-powered flight.\",\n \"Trains may also be equipped with inductive charging technology.\",\n \"For example, a locomotive may include an inductive coil, energy storage device, and control system, and a railroad segment may include a primary coil and power supply.\",\n \"A user, with a control unit, can command the train to move onto the segment, receiving a charge stored onboard.\",\n \"This segment could be, for example, a train station, coaling depot, or a plurality of segments spaced about a train track layout, each providing a charge to the train locomotive, or other cars being pulled by the train.\",\n \"Motor boats may also be equipped with inductive charging technology.\",\n \"A boat with a secondary coil can approach a dock, for example, which may include a securing device, such as a magnet, for holding the boat to the dock.\",\n \"Within the dock is a primary coil and power supply.\",\n \"The boat, when fully charged, is released by the dock or the user, and is able to drive about the surface of the water, or underwater, if used in a submersible craft.\",\n \"Although illustrative embodiments of the present disclosure have been described herein with reference to the accompanying drawings, it is to be understood that the disclosure is not limited to those precise embodiments, and that various other changes and modifications may be affected therein by one skilled in the art without departing from the scope or spirit of the disclosure.\",\n \"The above description is that of current embodiments of the invention.\",\n \"Various alterations and changes can be made without departing from the spirit and broader aspects of the invention as defined in the appended claims, which are to be interpreted in accordance with the principles of patent law including the doctrine of equivalents.\",\n \"Any reference to elements in the singular, for example, using the articles “a,” “an,” “the,” or “said,” is not to be construed as limiting the element to the singular.\"\n ]\n]"},"source":{"kind":"string","value":"Patent_15872028"}}},{"rowIdx":4493988,"cells":{"text":{"kind":"list like","value":[["METHOD AND APPARATUS FOR EXCHANGING COMMUNICATION SIGNALS","Aspects of the subject disclosure may include, for example, receiving, by each of a plurality of receivers, one of a plurality of electromagnetic waves, each electromagnetic wave of the plurality of electromagnetic waves guided by a different one of a plurality of twin-lead transmission lines, each twin-lead transmission line sharing a wire, and each electromagnetic wave of the plurality of electromagnetic waves including a different one of a plurality of communication signals, and obtaining, by each of the plurality of receivers, one of the plurality of communication signals.","Other embodiments are disclosed."],["1.A device, comprising: an antenna that facilitates receiving an electromagnetic wave of a plurality of electromagnetic waves, wherein each electromagnetic wave of the plurality of electromagnetic waves is guided by a different one of a plurality of twin-lead transmission lines, wherein the plurality of electromagnetic waves propagate along the plurality of twin-lead transmission lines without requiring an electrical return path, and wherein each electromagnetic wave of the plurality of electromagnetic waves conveys a different one of a plurality of communication signals; and a receiver that facilitates obtaining, from the electromagnetic wave that is received by the antenna, the different one of the plurality of communication signals.","2.The device of claim 1, wherein the antenna extracts energy from a twin-lead transmission line of the plurality of twin-lead transmission lines.","3.The device of claim 1, wherein the antenna comprises a dipole antenna having elements disposed between conductors of each of the plurality of twin-lead transmission lines.","4.The device of claim 1, wherein the antenna comprises a dipole antenna, and wherein an operating frequency of the different one of the communication signals is associated with dimensions of the dipole antenna.","5.The device of claim 1, wherein the plurality of electromagnetic waves operates in a non-optical frequency range.","6.The device of claim 1, wherein the plurality of twin-lead transmission lines comprise insulated conductors.","7.The device of claim 1, wherein the plurality of twin-lead transmission lines comprise uninsulated conductors.","8.The device of claim 1, wherein the plurality of twin-lead transmission lines comprise a plurality of twisted pairs of insulated conductors.","9.The device of claim 8, wherein each respective twin-lead transmission line of the plurality of twin-lead transmission lines corresponds to a respective twisted pair of insulated conductors of the plurality of twisted pairs of insulated conductors.","10.The device of claim 1, wherein the antenna is positioned between the plurality of twin-lead transmission lines.","11.A method, comprising: receiving, by an antenna of a communication device, a respective electromagnetic wave of a plurality of electromagnetic waves, the respective electromagnetic wave guided by a respective cable pair of a bundle of cables, wherein the respective electromagnetic wave propagates without requiring an electrical return path; and obtaining, by the antenna from the respective electromagnetic wave, a respective communication signal of a plurality of communication signals conveyed by the plurality of electromagnetic waves.","12.The method of claim 11, wherein the plurality of electromagnetic waves operates in a non-optical frequency range.","13.The method of claim 11, wherein the bundle of cables comprises a plurality of twisted pairs of uninsulated conductors.","14.The method of claim 11, wherein the bundle of cables comprises an insulated conductor, an uninsulated conductor, or combinations thereof.","15.The method of claim 11, wherein the bundle of cables comprises a plurality of twisted pairs of insulated conductors.","16.The method of claim 15, wherein the respective cable pair of the bundle of cables corresponds to a respective twisted pair of insulated conductors of the plurality of twisted pairs of insulated conductors.","17.The method of claim 16, wherein each respective twisted pair of insulated conductors of the plurality of twisted pairs of insulated conductors has a respective electrical return path that enables transmission of electrical signals.","18.The method of claim 11, wherein the plurality of electromagnetic waves employs phase shift keying, frequency shift keying, quadrature amplitude modulation, amplitude modulation, multi-carrier modulation, frequency division multiplexing, time division multiplexing, code division multiplexing, multiplexing via differing wave propagation modes, or any combinations thereof.","19.A device, comprising: a spacer that facilitates separation of a plurality of transmission lines; and an antenna that facilitates receiving an electromagnetic wave of a plurality of electromagnetic waves, wherein each electromagnetic wave of the plurality of electromagnetic waves is guided by a different one of the plurality of transmission lines, wherein each electromagnetic wave of the plurality of electromagnetic waves propagates without requiring an electrical return path, and wherein the antenna is coupled to the spacer.","20.The device of claim 19, wherein each electromagnetic wave of the plurality of electromagnetic waves conveys a different one of a plurality of communication signals."],[" BACKGROUND As smart phones and other portable devices increasingly become ubiquitous, and data usage increases, macrocell base station devices and existing wireless infrastructure in turn require higher bandwidth capability in order to address the increased demand.","To provide additional mobile bandwidth, small cell deployment is being pursued, with microcells and picocells providing coverage for much smaller areas than traditional macrocells.","In addition, most homes and businesses have grown to rely on broadband data access for services such as voice, video and Internet browsing, etc.","Broadband access networks include satellite, 4G or 5G wireless, power line communication, fiber, cable, and telephone networks."],[" BRIEF DESCRIPTION OF THE DRAWINGS Reference will now be made to the accompanying drawings, which are not necessarily drawn to scale, and wherein: FIG.","1 is a block diagram illustrating an example, non-limiting embodiment of a guided-wave communications system in accordance with various aspects described herein.","FIG.","2 is a block diagram illustrating an example, non-limiting embodiment of a transmission device in accordance with various aspects described herein.","FIG.","3 is a graphical diagram illustrating an example, non-limiting embodiment of an electromagnetic field distribution in accordance with various aspects described herein.","FIG.","4 is a graphical diagram illustrating an example, non-limiting embodiment of an electromagnetic field distribution in accordance with various aspects described herein.","FIG.","5A is a graphical diagram illustrating an example, non-limiting embodiment of a frequency response in accordance with various aspects described herein.","FIG.","5B is a graphical diagram illustrating example, non-limiting embodiments of a longitudinal cross-section of an insulated wire depicting fields of guided electromagnetic waves at various operating frequencies in accordance with various aspects described herein.","FIG.","6 is a graphical diagram illustrating an example, non-limiting embodiment of an electromagnetic field distribution in accordance with various aspects described herein.","FIG.","7 is a block diagram illustrating an example, non-limiting embodiment of an arc coupler in accordance with various aspects described herein.","FIG.","8 is a block diagram illustrating an example, non-limiting embodiment of an arc coupler in accordance with various aspects described herein.","FIG.","9A is a block diagram illustrating an example, non-limiting embodiment of a stub coupler in accordance with various aspects described herein.","FIG.","9B is a diagram illustrating an example, non-limiting embodiment of an electromagnetic distribution in accordance with various aspects described herein.","FIGS.","10A and 10B are block diagrams illustrating example, non-limiting embodiments of couplers and transceivers in accordance with various aspects described herein.","FIG.","11 is a block diagram illustrating an example, non-limiting embodiment of a dual stub coupler in accordance with various aspects described herein.","FIG.","12 is a block diagram illustrating an example, non-limiting embodiment of a repeater system in accordance with various aspects described herein.","FIG.","13 illustrates a block diagram illustrating an example, non-limiting embodiment of a bidirectional repeater in accordance with various aspects described herein.","FIG.","14 is a block diagram illustrating an example, non-limiting embodiment of a waveguide system in accordance with various aspects described herein.","FIG.","15 is a block diagram illustrating an example, non-limiting embodiment of a guided-wave communications system in accordance with various aspects described herein.","FIGS.","16A, 16B and 16C are block diagrams illustrating an example, non-limiting embodiment of a system for managing a communication system in accordance with various aspects described herein.","FIG.","16D illustrates a flow diagram of an example, non-limiting embodiment of a method in accordance with various aspects described herein.","FIG.","17A illustrates a flow diagram of an example, non-limiting embodiment of a method for detecting and mitigating disturbances occurring in a communication network of the system of FIGS.","16A, 16B, and 16C .","FIG.","17B illustrates a flow diagram of an example, non-limiting embodiment of a method for detecting and mitigating disturbances occurring in a communication network of the system of FIGS.","16A, 16B, and 16C .","FIG.","18 illustrates a block diagram illustrating an example, non-limiting embodiment of a cross-sectional view of transmission media in accordance with various aspects described herein.","FIG.","19 illustrates a block diagram illustrating an example, non-limiting embodiment of spacing device for coupling to the transmission media in accordance with various aspects described herein.","FIG.","20 illustrates a flow diagram of an example, non-limiting embodiment of a method in accordance with various aspects described herein.","FIG.","21 is a block diagram of an example, non-limiting embodiment of a computing environment in accordance with various aspects described herein.","FIG.","22 is a block diagram of an example, non-limiting embodiment of a mobile network platform in accordance with various aspects described herein.","FIG.","23 is a block diagram of an example, non-limiting embodiment of a communication device in accordance with various aspects described herein.","detailed-description description=\"Detailed Description\" end=\"lead\"?"],["CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of U.S. patent application Ser.","No.","15/665,632, filed Aug. 1, 2017, which is a continuation of U.S. patent application Ser.","No.","15/250,345, filed Aug. 29, 2016, now U.S. Pat.","No.","9,838,078, which is a continuation of U.S. patent application Ser.","No.","14/815,019, filed Jul.","31, 2015, now U.S. Pat.","No.","9,461,706.The contents of the foregoing are hereby incorporated by reference into this application as if set forth herein in full.","FIELD OF THE DISCLOSURE The subject disclosure relates to guided electromagnetic wave communications.","BACKGROUND As smart phones and other portable devices increasingly become ubiquitous, and data usage increases, macrocell base station devices and existing wireless infrastructure in turn require higher bandwidth capability in order to address the increased demand.","To provide additional mobile bandwidth, small cell deployment is being pursued, with microcells and picocells providing coverage for much smaller areas than traditional macrocells.","In addition, most homes and businesses have grown to rely on broadband data access for services such as voice, video and Internet browsing, etc.","Broadband access networks include satellite, 4G or 5G wireless, power line communication, fiber, cable, and telephone networks.","BRIEF DESCRIPTION OF THE DRAWINGS Reference will now be made to the accompanying drawings, which are not necessarily drawn to scale, and wherein: FIG.","1 is a block diagram illustrating an example, non-limiting embodiment of a guided-wave communications system in accordance with various aspects described herein.","FIG.","2 is a block diagram illustrating an example, non-limiting embodiment of a transmission device in accordance with various aspects described herein.","FIG.","3 is a graphical diagram illustrating an example, non-limiting embodiment of an electromagnetic field distribution in accordance with various aspects described herein.","FIG.","4 is a graphical diagram illustrating an example, non-limiting embodiment of an electromagnetic field distribution in accordance with various aspects described herein.","FIG.","5A is a graphical diagram illustrating an example, non-limiting embodiment of a frequency response in accordance with various aspects described herein.","FIG.","5B is a graphical diagram illustrating example, non-limiting embodiments of a longitudinal cross-section of an insulated wire depicting fields of guided electromagnetic waves at various operating frequencies in accordance with various aspects described herein.","FIG.","6 is a graphical diagram illustrating an example, non-limiting embodiment of an electromagnetic field distribution in accordance with various aspects described herein.","FIG.","7 is a block diagram illustrating an example, non-limiting embodiment of an arc coupler in accordance with various aspects described herein.","FIG.","8 is a block diagram illustrating an example, non-limiting embodiment of an arc coupler in accordance with various aspects described herein.","FIG.","9A is a block diagram illustrating an example, non-limiting embodiment of a stub coupler in accordance with various aspects described herein.","FIG.","9B is a diagram illustrating an example, non-limiting embodiment of an electromagnetic distribution in accordance with various aspects described herein.","FIGS.","10A and 10B are block diagrams illustrating example, non-limiting embodiments of couplers and transceivers in accordance with various aspects described herein.","FIG.","11 is a block diagram illustrating an example, non-limiting embodiment of a dual stub coupler in accordance with various aspects described herein.","FIG.","12 is a block diagram illustrating an example, non-limiting embodiment of a repeater system in accordance with various aspects described herein.","FIG.","13 illustrates a block diagram illustrating an example, non-limiting embodiment of a bidirectional repeater in accordance with various aspects described herein.","FIG.","14 is a block diagram illustrating an example, non-limiting embodiment of a waveguide system in accordance with various aspects described herein.","FIG.","15 is a block diagram illustrating an example, non-limiting embodiment of a guided-wave communications system in accordance with various aspects described herein.","FIGS.","16A, 16B and 16C are block diagrams illustrating an example, non-limiting embodiment of a system for managing a communication system in accordance with various aspects described herein.","FIG.","16D illustrates a flow diagram of an example, non-limiting embodiment of a method in accordance with various aspects described herein.","FIG.","17A illustrates a flow diagram of an example, non-limiting embodiment of a method for detecting and mitigating disturbances occurring in a communication network of the system of FIGS.","16A, 16B, and 16C.","FIG.","17B illustrates a flow diagram of an example, non-limiting embodiment of a method for detecting and mitigating disturbances occurring in a communication network of the system of FIGS.","16A, 16B, and 16C.","FIG.","18 illustrates a block diagram illustrating an example, non-limiting embodiment of a cross-sectional view of transmission media in accordance with various aspects described herein.","FIG.","19 illustrates a block diagram illustrating an example, non-limiting embodiment of spacing device for coupling to the transmission media in accordance with various aspects described herein.","FIG.","20 illustrates a flow diagram of an example, non-limiting embodiment of a method in accordance with various aspects described herein.","FIG.","21 is a block diagram of an example, non-limiting embodiment of a computing environment in accordance with various aspects described herein.","FIG.","22 is a block diagram of an example, non-limiting embodiment of a mobile network platform in accordance with various aspects described herein.","FIG.","23 is a block diagram of an example, non-limiting embodiment of a communication device in accordance with various aspects described herein.","DETAILED DESCRIPTION One or more embodiments are now described with reference to the drawings, wherein like reference numerals are used to refer to like elements throughout.","In the following description, for purposes of explanation, numerous details are set forth in order to provide a thorough understanding of the various embodiments.","It is evident, however, that the various embodiments can be practiced without these details (and without applying to any particular networked environment or standard).","In an embodiment, a guided wave communication system is presented for sending and receiving communication signals such as data or other signaling via guided electromagnetic waves.","The guided electromagnetic waves include, for example, surface waves or other electromagnetic waves that are bound to or guided by a transmission medium.","It will be appreciated that a variety of transmission media can be utilized with guided wave communications without departing from example embodiments.","Examples of such transmission media can include one or more of the following, either alone or in one or more combinations: wires, whether insulated or not, and whether single-stranded or multi-stranded; conductors of other shapes or configurations including wire bundles, cables, rods, rails, pipes; non-conductors such as dielectric pipes, rods, rails, or other dielectric members; combinations of conductors and dielectric materials; or other guided wave transmission media.","The inducement of guided electromagnetic waves on a transmission medium can be independent of any electrical potential, charge or current that is injected or otherwise transmitted through the transmission medium as part of an electrical circuit.","For example, in the case where the transmission medium is a wire, it is to be appreciated that while a small current in the wire may be formed in response to the propagation of the guided waves along the wire, this can be due to the propagation of the electromagnetic wave along the wire surface, and is not formed in response to electrical potential, charge or current that is injected into the wire as part of an electrical circuit.","The electromagnetic waves traveling on the wire therefore do not require a circuit to propagate along the wire surface.","The wire therefore is a single wire transmission line that is not part of a circuit.","Also, in some embodiments, a wire is not necessary, and the electromagnetic waves can propagate along a single line transmission medium that is not a wire.","More generally, “guided electromagnetic waves” or “guided waves” as described by the subject disclosure are affected by the presence of a physical object that is at least a part of the transmission medium (e.g., a bare wire or other conductor, a dielectric, an insulated wire, a conduit or other hollow element, a bundle of insulated wires that is coated, covered or surrounded by a dielectric or insulator or other wire bundle, or another form of solid, liquid or otherwise non-gaseous transmission medium) so as to be at least partially bound to or guided by the physical object and so as to propagate along a transmission path of the physical object.","Such a physical object can operate as at least a part of a transmission medium that guides, by way of an interface of the transmission medium (e.g., an outer surface, inner surface, an interior portion between the outer and the inner surfaces or other boundary between elements of the transmission medium), the propagation of guided electromagnetic waves, which in turn can carry energy, data and/or other signals along the transmission path from a sending device to a receiving device.","Unlike free space propagation of wireless signals such as unguided (or unbounded) electromagnetic waves that decrease in intensity inversely by the square of the distance traveled by the unguided electromagnetic waves, guided electromagnetic waves can propagate along a transmission medium with less loss in magnitude per unit distance than experienced by unguided electromagnetic waves.","Unlike electrical signals, guided electromagnetic waves can propagate from a sending device to a receiving device without requiring a separate electrical return path between the sending device and the receiving device.","As a consequence, guided electromagnetic waves can propagate from a sending device to a receiving device along a transmission medium having no conductive components (e.g., a dielectric strip), or via a transmission medium having no more than a single conductor (e.g., a single bare wire or insulated wire).","Even if a transmission medium includes one or more conductive components and the guided electromagnetic waves propagating along the transmission medium generate currents that flow in the one or more conductive components in a direction of the guided electromagnetic waves, such guided electromagnetic waves can propagate along the transmission medium from a sending device to a receiving device without requiring a flow of opposing currents on an electrical return path between the sending device and the receiving device.","In a non-limiting illustration, consider electrical systems that transmit and receive electrical signals between sending and receiving devices by way of conductive media.","Such systems generally rely on electrically separate forward and return paths.","For instance, consider a coaxial cable having a center conductor and a ground shield that are separated by an insulator.","Typically, in an electrical system a first terminal of a sending (or receiving) device can be connected to the center conductor, and a second terminal of the sending (or receiving) device can be connected to the ground shield.","If the sending device injects an electrical signal in the center conductor via the first terminal, the electrical signal will propagate along the center conductor causing forward currents in the center conductor, and return currents in the ground shield.","The same conditions apply for a two terminal receiving device.","In contrast, consider a guided wave communication system such as described in the subject disclosure, which can utilize different embodiments of a transmission medium (including among others a coaxial cable) for transmitting and receiving guided electromagnetic waves without an electrical return path.","In one embodiment, for example, the guided wave communication system of the subject disclosure can be configured to induce guided electromagnetic waves that propagate along an outer surface of a coaxial cable.","Although the guided electromagnetic waves will cause forward currents on the ground shield, the guided electromagnetic waves do not require return currents to enable the guided electromagnetic waves to propagate along the outer surface of the coaxial cable.","The same can be said of other transmission media used by a guided wave communication system for the transmission and reception of guided electromagnetic waves.","For example, guided electromagnetic waves induced by the guided wave communication system on an outer surface of a bare wire, or an insulated wire can propagate along the bare wire or the insulated bare wire without an electrical return path.","Consequently, electrical systems that require two or more conductors for carrying forward and reverse currents on separate conductors to enable the propagation of electrical signals injected by a sending device are distinct from guided wave systems that induce guided electromagnetic waves on an interface of a transmission medium without the need of an electrical return path to enable the propagation of the guided electromagnetic waves along the interface of the transmission medium.","It is further noted that guided electromagnetic waves as described in the subject disclosure can have an electromagnetic field structure that lies primarily or substantially outside of a transmission medium so as to be bound to or guided by the transmission medium and so as to propagate non-trivial distances on or along an outer surface of the transmission medium.","In other embodiments, guided electromagnetic waves can have an electromagnetic field structure that lies primarily or substantially inside a transmission medium so as to be bound to or guided by the transmission medium and so as to propagate non-trivial distances within the transmission medium.","In other embodiments, guided electromagnetic waves can have an electromagnetic field structure that lies partially inside and partially outside a transmission medium so as to be bound to or guided by the transmission medium and so as to propagate non-trivial distances along the transmission medium.","The desired electronic field structure in an embodiment may vary based upon a variety of factors, including the desired transmission distance, the characteristics of the transmission medium itself, and environmental conditions/characteristics outside of the transmission medium (e.g., presence of rain, fog, atmospheric conditions, etc.).","Various embodiments described herein relate to coupling devices, that can be referred to as “waveguide coupling devices”, “waveguide couplers” or more simply as “couplers”, “coupling devices” or “launchers” for launching and/or extracting guided electromagnetic waves to and from a transmission medium at millimeter-wave frequencies (e.g., 30 to 300 GHz), wherein the wavelength can be small compared to one or more dimensions of the coupling device and/or the transmission medium such as the circumference of a wire or other cross sectional dimension, or lower microwave frequencies such as 300 MHz to 30 GHz.","Transmissions can be generated to propagate as waves guided by a coupling device, such as: a strip, arc or other length of dielectric material; a horn, monopole, rod, slot or other antenna; an array of antennas; a magnetic resonant cavity, or other resonant coupler; a coil, a strip line, a waveguide or other coupling device.","In operation, the coupling device receives an electromagnetic wave from a transmitter or transmission medium.","The electromagnetic field structure of the electromagnetic wave can be carried inside the coupling device, outside the coupling device or some combination thereof.","When the coupling device is in close proximity to a transmission medium, at least a portion of an electromagnetic wave couples to or is bound to the transmission medium, and continues to propagate as guided electromagnetic waves.","In a reciprocal fashion, a coupling device can extract guided waves from a transmission medium and transfer these electromagnetic waves to a receiver.","According to an example embodiment, a surface wave is a type of guided wave that is guided by a surface of a transmission medium, such as an exterior or outer surface of the wire, or another surface of the wire that is adjacent to or exposed to another type of medium having different properties (e.g., dielectric properties).","Indeed, in an example embodiment, a surface of the wire that guides a surface wave can represent a transitional surface between two different types of media.","For example, in the case of a bare or uninsulated wire, the surface of the wire can be the outer or exterior conductive surface of the bare or uninsulated wire that is exposed to air or free space.","As another example, in the case of insulated wire, the surface of the wire can be the conductive portion of the wire that meets the insulator portion of the wire, or can otherwise be the insulator surface of the wire that is exposed to air or free space, or can otherwise be any material region between the insulator surface of the wire and the conductive portion of the wire that meets the insulator portion of the wire, depending upon the relative differences in the properties (e.g., dielectric properties) of the insulator, air, and/or the conductor and further dependent on the frequency and propagation mode or modes of the guided wave.","According to an example embodiment, the term “about” a wire or other transmission medium used in conjunction with a guided wave can include fundamental guided wave propagation modes such as a guided waves having a circular or substantially circular field distribution, a symmetrical electromagnetic field distribution (e.g., electric field, magnetic field, electromagnetic field, etc.)","or other fundamental mode pattern at least partially around a wire or other transmission medium.","In addition, when a guided wave propagates “about” a wire or other transmission medium, it can do so according to a guided wave propagation mode that includes not only the fundamental wave propagation modes (e.g., zero order modes), but additionally or alternatively non-fundamental wave propagation modes such as higher-order guided wave modes (e.g., 1st order modes, 2nd order modes, etc.","), asymmetrical modes and/or other guided (e.g., surface) waves that have non-circular field distributions around a wire or other transmission medium.","As used herein, the term “guided wave mode” refers to a guided wave propagation mode of a transmission medium, coupling device or other system component of a guided wave communication system.","For example, such non-circular field distributions can be unilateral or multi-lateral with one or more axial lobes characterized by relatively higher field strength and/or one or more nulls or null regions characterized by relatively low-field strength, zero-field strength or substantially zero-field strength.","Further, the field distribution can otherwise vary as a function of azimuthal orientation around the wire such that one or more angular regions around the wire have an electric or magnetic field strength (or combination thereof) that is higher than one or more other angular regions of azimuthal orientation, according to an example embodiment.","It will be appreciated that the relative orientations or positions of the guided wave higher order modes or asymmetrical modes can vary as the guided wave travels along the wire.","As used herein, the term “millimeter-wave” can refer to electromagnetic waves/signals that fall within the “millimeter-wave frequency band” of 30 GHz to 300 GHz.","The term “microwave” can refer to electromagnetic waves/signals that fall within a “microwave frequency band” of 300 MHz to 300 GHz.","The term “radio frequency” or “RF” can refer to electromagnetic waves/signals that fall within the “radio frequency band” of 10 kHz to 1 THz.","It is appreciated that wireless signals, electrical signals, and guided electromagnetic waves as described in the subject disclosure can be configured to operate at any desirable frequency range, such as, for example, at frequencies within, above or below millimeter-wave and/or microwave frequency bands.","In particular, when a coupling device or transmission medium includes a conductive element, the frequency of the guided electromagnetic waves that are carried by the coupling device and/or propagate along the transmission medium can be below the mean collision frequency of the electrons in the conductive element.","Further, the frequency of the guided electromagnetic waves that are carried by the coupling device and/or propagate along the transmission medium can be a non-optical frequency, e.g., a radio frequency below the range of optical frequencies that begins at 1 THz.","As used herein, the term “antenna” can refer to a device that is part of a transmitting or receiving system to transmit/radiate or receive wireless signals.","In accordance with one or more embodiments, a method can include receiving, by each of a plurality of launchers, one of a plurality of communication signals, each of the plurality of communication signals including different data, and launching, by each of the plurality of launchers, one of a plurality of electromagnetic waves, each electromagnetic wave of the plurality of electromagnetic waves guided by one of a plurality of twin-lead transmission lines formed between different ones of a plurality of power lines and a common cable, and each electromagnetic wave of the plurality of electromagnetic waves including a different one of the plurality of communication signals.","In accordance with one or more embodiments, a method can include receiving, by each of a plurality of receivers, one of a plurality of electromagnetic waves, each electromagnetic wave of the plurality of electromagnetic waves guided by a different one of a plurality of twin-lead transmission lines, each twin-lead transmission line sharing a wire, and each electromagnetic wave of the plurality of electromagnetic waves including a different one of a plurality of communication signals, and obtaining, by each of the plurality of receivers, one of the plurality of communication signals.","In accordance with one or more embodiments, a device can include a spacer that facilitates separation of a plurality of power lines and a common cable, and a plurality of transmitters coupled to the spacer, each of the plurality of transmitters facilitating transmission of one of a plurality of electromagnetic waves, each electromagnetic wave of the plurality of electromagnetic waves guided by one of a plurality of twin-lead transmission lines formed between different ones of the plurality of power lines and the common cable.","Referring now to FIG.","1, a block diagram 100 illustrating an example, non-limiting embodiment of a guided wave communications system is shown.","In operation, a transmission device 101 receives one or more communication signals 110 from a communication network or other communications device that includes data and generates guided waves 120 to convey the data via the transmission medium 125 to the transmission device 102.The transmission device 102 receives the guided waves 120 and converts them to communication signals 112 that include the data for transmission to a communications network or other communications device.","The guided waves 120 can be modulated to convey data via a modulation technique such as phase shift keying, frequency shift keying, quadrature amplitude modulation, amplitude modulation, multi-carrier modulation such as orthogonal frequency division multiplexing and via multiple access techniques such as frequency division multiplexing, time division multiplexing, code division multiplexing, multiplexing via differing wave propagation modes and via other modulation and access strategies.","The communication network or networks can include a wireless communication network such as a mobile data network, a cellular voice and data network, a wireless local area network (e.g., WiFi or an 802.xx network), a satellite communications network, a personal area network or other wireless network.","The communication network or networks can also include a wired communication network such as a telephone network, an Ethernet network, a local area network, a wide area network such as the Internet, a broadband access network, a cable network, a fiber optic network, or other wired network.","The communication devices can include a network edge device, bridge device or home gateway, a set-top box, broadband modem, telephone adapter, access point, base station, or other fixed communication device, a mobile communication device such as an automotive gateway or automobile, laptop computer, tablet, smartphone, cellular telephone, or other communication device.","In an example embodiment, the guided wave communication system 100 can operate in a bi-directional fashion where transmission device 102 receives one or more communication signals 112 from a communication network or device that includes other data and generates guided waves 122 to convey the other data via the transmission medium 125 to the transmission device 101.In this mode of operation, the transmission device 101 receives the guided waves 122 and converts them to communication signals 110 that include the other data for transmission to a communications network or device.","The guided waves 122 can be modulated to convey data via a modulation technique such as phase shift keying, frequency shift keying, quadrature amplitude modulation, amplitude modulation, multi-carrier modulation such as orthogonal frequency division multiplexing and via multiple access techniques such as frequency division multiplexing, time division multiplexing, code division multiplexing, multiplexing via differing wave propagation modes and via other modulation and access strategies.","The transmission medium 125 can include a cable having at least one inner portion surrounded by a dielectric material such as an insulator or other dielectric cover, coating or other dielectric material, the dielectric material having an outer surface and a corresponding circumference.","In an example embodiment, the transmission medium 125 operates as a single-wire transmission line to guide the transmission of an electromagnetic wave.","When the transmission medium 125 is implemented as a single wire transmission system, it can include a wire.","The wire can be insulated or uninsulated, and single-stranded or multi-stranded (e.g., braided).","In other embodiments, the transmission medium 125 can contain conductors of other shapes or configurations including wire bundles, cables, rods, rails, pipes.","In addition, the transmission medium 125 can include non-conductors such as dielectric pipes, rods, rails, or other dielectric members; combinations of conductors and dielectric materials, conductors without dielectric materials or other guided wave transmission media.","It should be noted that the transmission medium 125 can otherwise include any of the transmission media previously discussed.","Further, as previously discussed, the guided waves 120 and 122 can be contrasted with radio transmissions over free space/air or conventional propagation of electrical power or signals through the conductor of a wire via an electrical circuit.","In addition to the propagation of guided waves 120 and 122, the transmission medium 125 may optionally contain one or more wires that propagate electrical power or other communication signals in a conventional manner as a part of one or more electrical circuits.","Referring now to FIG.","2, a block diagram 200 illustrating an example, non-limiting embodiment of a transmission device is shown.","The transmission device 101 or 102 includes a communications interface (I/F) 205, a transceiver 210 and a coupler 220.In an example of operation, the communications interface 205 receives a communication signal 110 or 112 that includes data.","In various embodiments, the communications interface 205 can include a wireless interface for receiving a wireless communication signal in accordance with a wireless standard protocol such as LTE or other cellular voice and data protocol, WiFi or an 802.11 protocol, WIMAX protocol, Ultra Wideband protocol, Bluetooth protocol, Zigbee protocol, a direct broadcast satellite (DBS) or other satellite communication protocol or other wireless protocol.","In addition or in the alternative, the communications interface 205 includes a wired interface that operates in accordance with an Ethernet protocol, universal serial bus (USB) protocol, a data over cable service interface specification (DOCSIS) protocol, a digital subscriber line (DSL) protocol, a Firewire (IEEE 1394) protocol, or other wired protocol.","In additional to standards-based protocols, the communications interface 205 can operate in conjunction with other wired or wireless protocol.","In addition, the communications interface 205 can optionally operate in conjunction with a protocol stack that includes multiple protocol layers including a MAC protocol, transport protocol, application protocol, etc.","In an example of operation, the transceiver 210 generates an electromagnetic wave based on the communication signal 110 or 112 to convey the data.","The electromagnetic wave has at least one carrier frequency and at least one corresponding wavelength.","The carrier frequency can be within a millimeter-wave frequency band of 30 GHz-300 GHz, such as 60 GHz or a carrier frequency in the range of 30-40 GHz or a lower frequency band of 300 MHz-30 GHz in the microwave frequency range such as 26-30 GHz, 11 GHz, 6 GHz or 3 GHz, but it will be appreciated that other carrier frequencies are possible in other embodiments.","In one mode of operation, the transceiver 210 merely upconverts the communications signal or signals 110 or 112 for transmission of the electromagnetic signal in the microwave or millimeter-wave band as a guided electromagnetic wave that is guided by or bound to the transmission medium 125.In another mode of operation, the communications interface 205 either converts the communication signal 110 or 112 to a baseband or near baseband signal or extracts the data from the communication signal 110 or 112 and the transceiver 210 modulates a high-frequency carrier with the data, the baseband or near baseband signal for transmission.","It should be appreciated that the transceiver 210 can modulate the data received via the communication signal 110 or 112 to preserve one or more data communication protocols of the communication signal 110 or 112 either by encapsulation in the payload of a different protocol or by simple frequency shifting.","In the alternative, the transceiver 210 can otherwise translate the data received via the communication signal 110 or 112 to a protocol that is different from the data communication protocol or protocols of the communication signal 110 or 112.In an example of operation, the coupler 220 couples the electromagnetic wave to the transmission medium 125 as a guided electromagnetic wave to convey the communications signal or signals 110 or 112.While the prior description has focused on the operation of the transceiver 210 as a transmitter, the transceiver 210 can also operate to receive electromagnetic waves that convey other data from the single wire transmission medium via the coupler 220 and to generate communications signals 110 or 112, via communications interface 205 that includes the other data.","Consider embodiments where an additional guided electromagnetic wave conveys other data that also propagates along the transmission medium 125.The coupler 220 can also couple this additional electromagnetic wave from the transmission medium 125 to the transceiver 210 for reception.","The transmission device 101 or 102 includes an optional training controller 230.In an example embodiment, the training controller 230 is implemented by a standalone processor or a processor that is shared with one or more other components of the transmission device 101 or 102.The training controller 230 selects the carrier frequencies, modulation schemes and/or guided wave modes for the guided electromagnetic waves based on feedback data received by the transceiver 210 from at least one remote transmission device coupled to receive the guided electromagnetic wave.","In an example embodiment, a guided electromagnetic wave transmitted by a remote transmission device 101 or 102 conveys data that also propagates along the transmission medium 125.The data from the remote transmission device 101 or 102 can be generated to include the feedback data.","In operation, the coupler 220 also couples the guided electromagnetic wave from the transmission medium 125 and the transceiver receives the electromagnetic wave and processes the electromagnetic wave to extract the feedback data.","In an example embodiment, the training controller 230 operates based on the feedback data to evaluate a plurality of candidate frequencies, modulation schemes and/or transmission modes to select a carrier frequency, modulation scheme and/or transmission mode to enhance performance, such as throughput, signal strength, reduce propagation loss, etc.","Consider the following example: a transmission device 101 begins operation under control of the training controller 230 by sending a plurality of guided waves as test signals such as pilot waves or other test signals at a corresponding plurality of candidate frequencies and/or candidate modes directed to a remote transmission device 102 coupled to the transmission medium 125.The guided waves can include, in addition or in the alternative, test data.","The test data can indicate the particular candidate frequency and/or guide-wave mode of the signal.","In an embodiment, the training controller 230 at the remote transmission device 102 receives the test signals and/or test data from any of the guided waves that were properly received and determines the best candidate frequency and/or guided wave mode, a set of acceptable candidate frequencies and/or guided wave modes, or a rank ordering of candidate frequencies and/or guided wave modes.","This selection of candidate frequenc(ies) or/and guided-mode(s) are generated by the training controller 230 based on one or more optimizing criteria such as received signal strength, bit error rate, packet error rate, signal to noise ratio, propagation loss, etc.","The training controller 230 generates feedback data that indicates the selection of candidate frequenc(ies) or/and guided wave mode(s) and sends the feedback data to the transceiver 210 for transmission to the transmission device 101.The transmission device 101 and 102 can then communicate data with one another based on the selection of candidate frequenc(ies) or/and guided wave mode(s).","In other embodiments, the guided electromagnetic waves that contain the test signals and/or test data are reflected back, repeated back or otherwise looped back by the remote transmission device 102 to the transmission device 101 for reception and analysis by the training controller 230 of the transmission device 101 that initiated these waves.","For example, the transmission device 101 can send a signal to the remote transmission device 102 to initiate a test mode where a physical reflector is switched on the line, a termination impedance is changed to cause reflections, a loop back mode is switched on to couple electromagnetic waves back to the source transmission device 102, and/or a repeater mode is enabled to amplify and retransmit the electromagnetic waves back to the source transmission device 102.The training controller 230 at the source transmission device 102 receives the test signals and/or test data from any of the guided waves that were properly received and determines selection of candidate frequenc(ies) or/and guided wave mode(s).","While the procedure above has been described in a start-up or initialization mode of operation, each transmission device 101 or 102 can send test signals, evaluate candidate frequencies or guided wave modes via non-test such as normal transmissions or otherwise evaluate candidate frequencies or guided wave modes at other times or continuously as well.","In an example embodiment, the communication protocol between the transmission devices 101 and 102 can include an on-request or periodic test mode where either full testing or more limited testing of a subset of candidate frequencies and guided wave modes are tested and evaluated.","In other modes of operation, the re-entry into such a test mode can be triggered by a degradation of performance due to a disturbance, weather conditions, etc.","In an example embodiment, the receiver bandwidth of the transceiver 210 is either sufficiently wide or swept to receive all candidate frequencies or can be selectively adjusted by the training controller 230 to a training mode where the receiver bandwidth of the transceiver 210 is sufficiently wide or swept to receive all candidate frequencies.","Referring now to FIG.","3, a graphical diagram 300 illustrating an example, non-limiting embodiment of an electromagnetic field distribution is shown.","In this embodiment, a transmission medium 125 in air includes an inner conductor 301 and an insulating jacket 302 of dielectric material, as shown in cross section.","The diagram 300 includes different gray-scales that represent differing electromagnetic field strengths generated by the propagation of the guided wave having an asymmetrical and non-fundamental guided wave mode.","In particular, the electromagnetic field distribution corresponds to a modal “sweet spot” that enhances guided electromagnetic wave propagation along an insulated transmission medium and reduces end-to-end transmission loss.","In this particular mode, electromagnetic waves are guided by the transmission medium 125 to propagate along an outer surface of the transmission medium—in this case, the outer surface of the insulating jacket 302.Electromagnetic waves are partially embedded in the insulator and partially radiating on the outer surface of the insulator.","In this fashion, electromagnetic waves are “lightly” coupled to the insulator so as to enable electromagnetic wave propagation at long distances with low propagation loss.","As shown, the guided wave has a field structure that lies primarily or substantially outside of the transmission medium 125 that serves to guide the electromagnetic waves.","The regions inside the conductor 301 have little or no field.","Likewise regions inside the insulating jacket 302 have low field strength.","The majority of the electromagnetic field strength is distributed in the lobes 304 at the outer surface of the insulating jacket 302 and in close proximity thereof.","The presence of an asymmetric guided wave mode is shown by the high electromagnetic field strengths at the top and bottom of the outer surface of the insulating jacket 302 (in the orientation of the diagram)—as opposed to very small field strengths on the other sides of the insulating jacket 302.The example shown corresponds to a 38 GHz electromagnetic wave guided by a wire with a diameter of 1.1 cm and a dielectric insulation of thickness of 0.36 cm.","Because the electromagnetic wave is guided by the transmission medium 125 and the majority of the field strength is concentrated in the air outside of the insulating jacket 302 within a limited distance of the outer surface, the guided wave can propagate longitudinally down the transmission medium 125 with very low loss.","In the example shown, this “limited distance” corresponds to a distance from the outer surface that is less than half the largest cross sectional dimension of the transmission medium 125.In this case, the largest cross sectional dimension of the wire corresponds to the overall diameter of 1.82 cm, however, this value can vary with the size and shape of the transmission medium 125.For example, should the transmission medium 125 be of a rectangular shape with a height of 0.3 cm and a width of 0.4 cm, the largest cross sectional dimension would be the diagonal of 0.5 cm and the corresponding limited distance would be 0.25 cm.","The dimensions of the area containing the majority of the field strength also vary with the frequency, and in general, increase as carrier frequencies decrease.","It should also be noted that the components of a guided wave communication system, such as couplers and transmission media can have their own cut-off frequencies for each guided wave mode.","The cut-off frequency generally sets forth the lowest frequency that a particular guided wave mode is designed to be supported by that particular component.","In an example embodiment, the particular asymmetric mode of propagation shown is induced on the transmission medium 125 by an electromagnetic wave having a frequency that falls within a limited range (such as Fc to 2Fc) of the lower cut-off frequency Fc for this particular asymmetric mode.","The lower cut-off frequency Fc is particular to the characteristics of transmission medium 125.For embodiments as shown that include an inner conductor 301 surrounded by an insulating jacket 302, this cutoff frequency can vary based on the dimensions and properties of the insulating jacket 302 and potentially the dimensions and properties of the inner conductor 301 and can be determined experimentally to have a desired mode pattern.","It should be noted however, that similar effects can be found for a hollow dielectric or insulator without an inner conductor.","In this case, the cutoff frequency can vary based on the dimensions and properties of the hollow dielectric or insulator.","At frequencies lower than the lower cut-off frequency, the asymmetric mode is difficult to induce in the transmission medium 125 and fails to propagate for all but trivial distances.","As the frequency increases above the limited range of frequencies about the cut-off frequency, the asymmetric mode shifts more and more inward of the insulating jacket 302.At frequencies much larger than the cut-off frequency, the field strength is no longer concentrated outside of the insulating jacket, but primarily inside of the insulating jacket 302.While the transmission medium 125 provides strong guidance to the electromagnetic wave and propagation is still possible, ranges are more limited by increased losses due to propagation within the insulating jacket 302—as opposed to the surrounding air.","Referring now to FIG.","4, a graphical diagram 400 illustrating an example, non-limiting embodiment of an electromagnetic field distribution is shown.","In particular, a cross section diagram 400, similar to FIG.","3 is shown with common reference numerals used to refer to similar elements.","The example shown corresponds to a 60 GHz wave guided by a wire with a diameter of 1.1 cm and a dielectric insulation of thickness of 0.36 cm.","Because the frequency of the guided wave is above the limited range of the cut-off frequency of this particular asymmetric mode, much of the field strength has shifted inward of the insulating jacket 302.In particular, the field strength is concentrated primarily inside of the insulating jacket 302.While the transmission medium 125 provides strong guidance to the electromagnetic wave and propagation is still possible, ranges are more limited when compared with the embodiment of FIG.","3, by increased losses due to propagation within the insulating jacket 302.Referring now to FIG.","5A, a graphical diagram illustrating an example, non-limiting embodiment of a frequency response is shown.","In particular, diagram 500 presents a graph of end-to-end loss (in dB) as a function of frequency, overlaid with electromagnetic field distributions 510, 520 and 530 at three points for a 200 cm insulated medium voltage wire.","The boundary between the insulator and the surrounding air is represented by reference numeral 525 in each electromagnetic field distribution.","As discussed in conjunction with FIG.","3, an example of a desired asymmetric mode of propagation shown is induced on the transmission medium 125 by an electromagnetic wave having a frequency that falls within a limited range (such as Fc to 2Fc) of the lower cut-off frequency Fc of the transmission medium for this particular asymmetric mode.","In particular, the electromagnetic field distribution 520 at 6 GHz falls within this modal “sweet spot” that enhances electromagnetic wave propagation along an insulated transmission medium and reduces end-to-end transmission loss.","In this particular mode, guided waves are partially embedded in the insulator and partially radiating on the outer surface of the insulator.","In this fashion, the electromagnetic waves are “lightly” coupled to the insulator so as to enable guided electromagnetic wave propagation at long distances with low propagation loss.","At lower frequencies represented by the electromagnetic field distribution 510 at 3 GHz, the asymmetric mode radiates more heavily generating higher propagation losses.","At higher frequencies represented by the electromagnetic field distribution 530 at 9 GHz, the asymmetric mode shifts more and more inward of the insulating jacket providing too much absorption, again generating higher propagation losses.","Referring now to FIG.","5B, a graphical diagram 550 illustrating example, non-limiting embodiments of a longitudinal cross-section of a transmission medium 125, such as an insulated wire, depicting fields of guided electromagnetic waves at various operating frequencies is shown.","As shown in diagram 556, when the guided electromagnetic waves are at approximately the cutoff frequency (fc) corresponding to the modal “sweet spot”, the guided electromagnetic waves are loosely coupled to the insulated wire so that absorption is reduced, and the fields of the guided electromagnetic waves are bound sufficiently to reduce the amount radiated into the environment (e.g., air).","Because absorption and radiation of the fields of the guided electromagnetic waves is low, propagation losses are consequently low, enabling the guided electromagnetic waves to propagate for longer distances.","As shown in diagram 554, propagation losses increase when an operating frequency of the guide electromagnetic waves increases above about two-times the cutoff frequency (fc)—or as referred to, above the range of the “sweet spot”.","More of the field strength of the electromagnetic wave is driven inside the insulating layer, increasing propagation losses.","At frequencies much higher than the cutoff frequency (fc) the guided electromagnetic waves are strongly bound to the insulated wire as a result of the fields emitted by the guided electromagnetic waves being concentrated in the insulation layer of the wire, as shown in diagram 552.This in turn raises propagation losses further due to absorption of the guided electromagnetic waves by the insulation layer.","Similarly, propagation losses increase when the operating frequency of the guided electromagnetic waves is substantially below the cutoff frequency (fc), as shown in diagram 558.At frequencies much lower than the cutoff frequency (fc) the guided electromagnetic waves are weakly (or nominally) bound to the insulated wire and thereby tend to radiate into the environment (e.g., air), which in turn, raises propagation losses due to radiation of the guided electromagnetic waves.","Referring now to FIG.","6, a graphical diagram 600 illustrating an example, non-limiting embodiment of an electromagnetic field distribution is shown.","In this embodiment, a transmission medium 602 is a bare wire, as shown in cross section.","The diagram 300 includes different gray-scales that represent differing electromagnetic field strengths generated by the propagation of a guided wave having a symmetrical and fundamental guided wave mode at a single carrier frequency.","In this particular mode, electromagnetic waves are guided by the transmission medium 602 to propagate along an outer surface of the transmission medium—in this case, the outer surface of the bare wire.","Electromagnetic waves are “lightly” coupled to the wire so as to enable electromagnetic wave propagation at long distances with low propagation loss.","As shown, the guided wave has a field structure that lies substantially outside of the transmission medium 602 that serves to guide the electromagnetic waves.","The regions inside the conductor 602 have little or no field.","Referring now to FIG.","7, a block diagram 700 illustrating an example, non-limiting embodiment of an arc coupler is shown.","In particular a coupling device is presented for use in a transmission device, such as transmission device 101 or 102 presented in conjunction with FIG.","1.The coupling device includes an arc coupler 704 coupled to a transmitter circuit 712 and termination or damper 714.The arc coupler 704 can be made of a dielectric material, or other low-loss insulator (e.g., Teflon, polyethylene, etc.","), or made of a conducting (e.g., metallic, non-metallic, etc.)","material, or any combination of the foregoing materials.","As shown, the arc coupler 704 operates as a waveguide and has a wave 706 propagating as a guided wave about a waveguide surface of the arc coupler 704.In the embodiment shown, at least a portion of the arc coupler 704 can be placed near a wire 702 or other transmission medium, (such as transmission medium 125), in order to facilitate coupling between the arc coupler 704 and the wire 702 or other transmission medium, as described herein to launch the guided wave 708 on the wire.","The arc coupler 704 can be placed such that a portion of the curved arc coupler 704 is tangential to, and parallel or substantially parallel to the wire 702.The portion of the arc coupler 704 that is parallel to the wire can be an apex of the curve, or any point where a tangent of the curve is parallel to the wire 702.When the arc coupler 704 is positioned or placed thusly, the wave 706 travelling along the arc coupler 704 couples, at least in part, to the wire 702, and propagates as guided wave 708 around or about the wire surface of the wire 702 and longitudinally along the wire 702.The guided wave 708 can be characterized as a surface wave or other electromagnetic wave that is guided by or bound to the wire 702 or other transmission medium.","A portion of the wave 706 that does not couple to the wire 702 propagates as a wave 710 along the arc coupler 704.It will be appreciated that the arc coupler 704 can be configured and arranged in a variety of positions in relation to the wire 702 to achieve a desired level of coupling or non-coupling of the wave 706 to the wire 702.For example, the curvature and/or length of the arc coupler 704 that is parallel or substantially parallel, as well as its separation distance (which can include zero separation distance in an embodiment), to the wire 702 can be varied without departing from example embodiments.","Likewise, the arrangement of arc coupler 704 in relation to the wire 702 may be varied based upon considerations of the respective intrinsic characteristics (e.g., thickness, composition, electromagnetic properties, etc.)","of the wire 702 and the arc coupler 704, as well as the characteristics (e.g., frequency, energy level, etc.)","of the waves 706 and 708.The guided wave 708 stays parallel or substantially parallel to the wire 702, even as the wire 702 bends and flexes.","Bends in the wire 702 can increase transmission losses, which are also dependent on wire diameters, frequency, and materials.","If the dimensions of the arc coupler 704 are chosen for efficient power transfer, most of the power in the wave 706 is transferred to the wire 702, with little power remaining in wave 710.It will be appreciated that the guided wave 708 can still be multi-modal in nature (discussed herein), including having modes that are non-fundamental or asymmetric, while traveling along a path that is parallel or substantially parallel to the wire 702, with or without a fundamental transmission mode.","In an embodiment, non-fundamental or asymmetric modes can be utilized to minimize transmission losses and/or obtain increased propagation distances.","It is noted that the term parallel is generally a geometric construct which often is not exactly achievable in real systems.","Accordingly, the term parallel as utilized in the subject disclosure represents an approximation rather than an exact configuration when used to describe embodiments disclosed in the subject disclosure.","In an embodiment, substantially parallel can include approximations that are within 30 degrees of true parallel in all dimensions.","In an embodiment, the wave 706 can exhibit one or more wave propagation modes.","The arc coupler modes can be dependent on the shape and/or design of the coupler 704.The one or more arc coupler modes of wave 706 can generate, influence, or impact one or more wave propagation modes of the guided wave 708 propagating along wire 702.It should be particularly noted however that the guided wave modes present in the guided wave 706 may be the same or different from the guided wave modes of the guided wave 708.In this fashion, one or more guided wave modes of the guided wave 706 may not be transferred to the guided wave 708, and further one or more guided wave modes of guided wave 708 may not have been present in guided wave 706.It should also be noted that the cut-off frequency of the arc coupler 704 for a particular guided wave mode may be different than the cutoff frequency of the wire 702 or other transmission medium for that same mode.","For example, while the wire 702 or other transmission medium may be operated slightly above its cutoff frequency for a particular guided wave mode, the arc coupler 704 may be operated well above its cut-off frequency for that same mode for low loss, slightly below its cut-off frequency for that same mode to, for example, induce greater coupling and power transfer, or some other point in relation to the arc coupler's cutoff frequency for that mode.","In an embodiment, the wave propagation modes on the wire 702 can be similar to the arc coupler modes since both waves 706 and 708 propagate about the outside of the arc coupler 704 and wire 702 respectively.","In some embodiments, as the wave 706 couples to the wire 702, the modes can change form, or new modes can be created or generated, due to the coupling between the arc coupler 704 and the wire 702.For example, differences in size, material, and/or impedances of the arc coupler 704 and wire 702 may create additional modes not present in the arc coupler modes and/or suppress some of the arc coupler modes.","The wave propagation modes can comprise the fundamental transverse electromagnetic mode (Quasi-TEM00), where only small electric and/or magnetic fields extend in the direction of propagation, and the electric and magnetic fields extend radially outwards while the guided wave propagates along the wire.","This guided wave mode can be donut shaped, where few of the electromagnetic fields exist within the arc coupler 704 or wire 702.Waves 706 and 708 can comprise a fundamental TEM mode where the fields extend radially outwards, and also comprise other, non-fundamental (e.g., asymmetric, higher-level, etc.)","modes.","While particular wave propagation modes are discussed above, other wave propagation modes are likewise possible such as transverse electric (TE) and transverse magnetic (TM) modes, based on the frequencies employed, the design of the arc coupler 704, the dimensions and composition of the wire 702, as well as its surface characteristics, its insulation if present, the electromagnetic properties of the surrounding environment, etc.","It should be noted that, depending on the frequency, the electrical and physical characteristics of the wire 702 and the particular wave propagation modes that are generated, guided wave 708 can travel along the conductive surface of an oxidized uninsulated wire, an unoxidized uninsulated wire, an insulated wire and/or along the insulating surface of an insulated wire.","In an embodiment, a diameter of the arc coupler 704 is smaller than the diameter of the wire 702.For the millimeter-band wavelength being used, the arc coupler 704 supports a single waveguide mode that makes up wave 706.This single waveguide mode can change as it couples to the wire 702 as guided wave 708.If the arc coupler 704 were larger, more than one waveguide mode can be supported, but these additional waveguide modes may not couple to the wire 702 as efficiently, and higher coupling losses can result.","However, in some alternative embodiments, the diameter of the arc coupler 704 can be equal to or larger than the diameter of the wire 702, for example, where higher coupling losses are desirable or when used in conjunction with other techniques to otherwise reduce coupling losses (e.g., impedance matching with tapering, etc.).","In an embodiment, the wavelength of the waves 706 and 708 are comparable in size, or smaller than a circumference of the arc coupler 704 and the wire 702.In an example, if the wire 702 has a diameter of 0.5 cm, and a corresponding circumference of around 1.5 cm, the wavelength of the transmission is around 1.5 cm or less, corresponding to a frequency of 70 GHz or greater.","In another embodiment, a suitable frequency of the transmission and the carrier-wave signal is in the range of 30-100 GHz, perhaps around 30-60 GHz, and around 38 GHz in one example.","In an embodiment, when the circumference of the arc coupler 704 and wire 702 is comparable in size to, or greater, than a wavelength of the transmission, the waves 706 and 708 can exhibit multiple wave propagation modes including fundamental and/or non-fundamental (symmetric and/or asymmetric) modes that propagate over sufficient distances to support various communication systems described herein.","The waves 706 and 708 can therefore comprise more than one type of electric and magnetic field configuration.","In an embodiment, as the guided wave 708 propagates down the wire 702, the electrical and magnetic field configurations will remain the same from end to end of the wire 702.In other embodiments, as the guided wave 708 encounters interference (distortion or obstructions) or loses energy due to transmission losses or scattering, the electric and magnetic field configurations can change as the guided wave 708 propagates down wire 702.In an embodiment, the arc coupler 704 can be composed of nylon, Teflon, polyethylene, a polyamide, or other plastics.","In other embodiments, other dielectric materials are possible.","The wire surface of wire 702 can be metallic with either a bare metallic surface, or can be insulated using plastic, dielectric, insulator or other coating, jacket or sheathing.","In an embodiment, a dielectric or otherwise non-conducting/insulated waveguide can be paired with either a bare/metallic wire or insulated wire.","In other embodiments, a metallic and/or conductive waveguide can be paired with a bare/metallic wire or insulated wire.","In an embodiment, an oxidation layer on the bare metallic surface of the wire 702 (e.g., resulting from exposure of the bare metallic surface to oxygen/air) can also provide insulating or dielectric properties similar to those provided by some insulators or sheathings.","It is noted that the graphical representations of waves 706, 708 and 710 are presented merely to illustrate the principles that wave 706 induces or otherwise launches a guided wave 708 on a wire 702 that operates, for example, as a single wire transmission line.","Wave 710 represents the portion of wave 706 that remains on the arc coupler 704 after the generation of guided wave 708.The actual electric and magnetic fields generated as a result of such wave propagation may vary depending on the frequencies employed, the particular wave propagation mode or modes, the design of the arc coupler 704, the dimensions and composition of the wire 702, as well as its surface characteristics, its optional insulation, the electromagnetic properties of the surrounding environment, etc.","It is noted that arc coupler 704 can include a termination circuit or damper 714 at the end of the arc coupler 704 that can absorb leftover radiation or energy from wave 710.The termination circuit or damper 714 can prevent and/or minimize the leftover radiation or energy from wave 710 reflecting back toward transmitter circuit 712.In an embodiment, the termination circuit or damper 714 can include termination resistors, and/or other components that perform impedance matching to attenuate reflection.","In some embodiments, if the coupling efficiencies are high enough, and/or wave 710 is sufficiently small, it may not be necessary to use a termination circuit or damper 714.For the sake of simplicity, these transmitter 712 and termination circuits or dampers 714 may not be depicted in the other figures, but in those embodiments, transmitter and termination circuits or dampers may possibly be used.","Further, while a single arc coupler 704 is presented that generates a single guided wave 708, multiple arc couplers 704 placed at different points along the wire 702 and/or at different azimuthal orientations about the wire can be employed to generate and receive multiple guided waves 708 at the same or different frequencies, at the same or different phases, at the same or different wave propagation modes.","FIG.","8, a block diagram 800 illustrating an example, non-limiting embodiment of an arc coupler is shown.","In the embodiment shown, at least a portion of the coupler 704 can be placed near a wire 702 or other transmission medium, (such as transmission medium 125), in order to facilitate coupling between the arc coupler 704 and the wire 702 or other transmission medium, to extract a portion of the guided wave 806 as a guided wave 808 as described herein.","The arc coupler 704 can be placed such that a portion of the curved arc coupler 704 is tangential to, and parallel or substantially parallel to the wire 702.The portion of the arc coupler 704 that is parallel to the wire can be an apex of the curve, or any point where a tangent of the curve is parallel to the wire 702.When the arc coupler 704 is positioned or placed thusly, the wave 806 travelling along the wire 702 couples, at least in part, to the arc coupler 704, and propagates as guided wave 808 along the arc coupler 704 to a receiving device (not expressly shown).","A portion of the wave 806 that does not couple to the arc coupler propagates as wave 810 along the wire 702 or other transmission medium.","In an embodiment, the wave 806 can exhibit one or more wave propagation modes.","The arc coupler modes can be dependent on the shape and/or design of the coupler 704.The one or more modes of guided wave 806 can generate, influence, or impact one or more guide-wave modes of the guided wave 808 propagating along the arc coupler 704.It should be particularly noted however that the guided wave modes present in the guided wave 806 may be the same or different from the guided wave modes of the guided wave 808.In this fashion, one or more guided wave modes of the guided wave 806 may not be transferred to the guided wave 808, and further one or more guided wave modes of guided wave 808 may not have been present in guided wave 806.Referring now to FIG.","9A, a block diagram 900 illustrating an example, non-limiting embodiment of a stub coupler is shown.","In particular a coupling device that includes stub coupler 904 is presented for use in a transmission device, such as transmission device 101 or 102 presented in conjunction with FIG.","1.The stub coupler 904 can be made of a dielectric material, or other low-loss insulator (e.g., Teflon, polyethylene and etc.","), or made of a conducting (e.g., metallic, non-metallic, etc.)","material, or any combination of the foregoing materials.","As shown, the stub coupler 904 operates as a waveguide and has a wave 906 propagating as a guided wave about a waveguide surface of the stub coupler 904.In the embodiment shown, at least a portion of the stub coupler 904 can be placed near a wire 702 or other transmission medium, (such as transmission medium 125), in order to facilitate coupling between the stub coupler 904 and the wire 702 or other transmission medium, as described herein to launch the guided wave 908 on the wire.","In an embodiment, the stub coupler 904 is curved, and an end of the stub coupler 904 can be tied, fastened, or otherwise mechanically coupled to a wire 702.When the end of the stub coupler 904 is fastened to the wire 702, the end of the stub coupler 904 is parallel or substantially parallel to the wire 702.Alternatively, another portion of the dielectric waveguide beyond an end can be fastened or coupled to wire 702 such that the fastened or coupled portion is parallel or substantially parallel to the wire 702.The fastener 910 can be a nylon cable tie or other type of non-conducting/dielectric material that is either separate from the stub coupler 904 or constructed as an integrated component of the stub coupler 904.The stub coupler 904 can be adjacent to the wire 702 without surrounding the wire 702.Like the arc coupler 704 described in conjunction with FIG.","7, when the stub coupler 904 is placed with the end parallel to the wire 702, the guided wave 906 travelling along the stub coupler 904 couples to the wire 702, and propagates as guided wave 908 about the wire surface of the wire 702.In an example embodiment, the guided wave 908 can be characterized as a surface wave or other electromagnetic wave.","It is noted that the graphical representations of waves 906 and 908 are presented merely to illustrate the principles that wave 906 induces or otherwise launches a guided wave 908 on a wire 702 that operates, for example, as a single wire transmission line.","The actual electric and magnetic fields generated as a result of such wave propagation may vary depending on one or more of the shape and/or design of the coupler, the relative position of the dielectric waveguide to the wire, the frequencies employed, the design of the stub coupler 904, the dimensions and composition of the wire 702, as well as its surface characteristics, its optional insulation, the electromagnetic properties of the surrounding environment, etc.","In an embodiment, an end of stub coupler 904 can taper towards the wire 702 in order to increase coupling efficiencies.","Indeed, the tapering of the end of the stub coupler 904 can provide impedance matching to the wire 702 and reduce reflections, according to an example embodiment of the subject disclosure.","For example, an end of the stub coupler 904 can be gradually tapered in order to obtain a desired level of coupling between waves 906 and 908 as illustrated in FIG.","9A.","In an embodiment, the fastener 910 can be placed such that there is a short length of the stub coupler 904 between the fastener 910 and an end of the stub coupler 904.Maximum coupling efficiencies are realized in this embodiment when the length of the end of the stub coupler 904 that is beyond the fastener 910 is at least several wavelengths long for whatever frequency is being transmitted.","Turning now to FIG.","9B, a diagram 950 illustrating an example, non-limiting embodiment of an electromagnetic distribution in accordance with various aspects described herein is shown.","In particular, an electromagnetic distribution is presented in two dimensions for a transmission device that includes coupler 952, shown in an example stub coupler constructed of a dielectric material.","The coupler 952 couples an electromagnetic wave for propagation as a guided wave along an outer surface of a wire 702 or other transmission medium.","The coupler 952 guides the electromagnetic wave to a junction at x0 via a symmetrical guided wave mode.","While some of the energy of the electromagnetic wave that propagates along the coupler 952 is outside of the coupler 952, the majority of the energy of this electromagnetic wave is contained within the coupler 952.The junction at x0 couples the electromagnetic wave to the wire 702 or other transmission medium at an azimuthal angle corresponding to the bottom of the transmission medium.","This coupling induces an electromagnetic wave that is guided to propagate along the outer surface of the wire 702 or other transmission medium via at least one guided wave mode in direction 956.The majority of the energy of the guided electromagnetic wave is outside or, but in close proximity to the outer surface of the wire 702 or other transmission medium.","In the example shown, the junction at x0 forms an electromagnetic wave that propagates via both a symmetrical mode and at least one asymmetrical surface mode, such as the first order mode presented in conjunction with FIG.","3, that skims the surface of the wire 702 or other transmission medium.","It is noted that the graphical representations of guided waves are presented merely to illustrate an example of guided wave coupling and propagation.","The actual electric and magnetic fields generated as a result of such wave propagation may vary depending on the frequencies employed, the design and/or configuration of the coupler 952, the dimensions and composition of the wire 702 or other transmission medium, as well as its surface characteristics, its insulation if present, the electromagnetic properties of the surrounding environment, etc.","Turning now to FIG.","10A, illustrated is a block diagram 1000 of an example, non-limiting embodiment of a coupler and transceiver system in accordance with various aspects described herein.","The system is an example of transmission device 101 or 102.In particular, the communication interface 1008 is an example of communications interface 205, the stub coupler 1002 is an example of coupler 220, and the transmitter/receiver device 1006, diplexer 1016, power amplifier 1014, low noise amplifier 1018, frequency mixers 1010 and 1020 and local oscillator 1012 collectively form an example of transceiver 210.In operation, the transmitter/receiver device 1006 launches and receives waves (e.g., guided wave 1004 onto stub coupler 1002).","The guided waves 1004 can be used to transport signals received from and sent to a host device, base station, mobile devices, a building or other device by way of a communications interface 1008.The communications interface 1008 can be an integral part of system 1000.Alternatively, the communications interface 1008 can be tethered to system 1000.The communications interface 1008 can comprise a wireless interface for interfacing to the host device, base station, mobile devices, a building or other device utilizing any of various wireless signaling protocols (e.g., LTE, WiFi, WiMAX, IEEE 802.xx, etc.)","including an infrared protocol such as an infrared data association (IrDA) protocol or other line of sight optical protocol.","The communications interface 1008 can also comprise a wired interface such as a fiber optic line, coaxial cable, twisted pair, category 5 (CAT-5) cable or other suitable wired or optical mediums for communicating with the host device, base station, mobile devices, a building or other device via a protocol such as an Ethernet protocol, universal serial bus (USB) protocol, a data over cable service interface specification (DOCSIS) protocol, a digital subscriber line (DSL) protocol, a Firewire (IEEE 1394) protocol, or other wired or optical protocol.","For embodiments where system 1000 functions as a repeater, the communications interface 1008 may not be necessary.","The output signals (e.g., Tx) of the communications interface 1008 can be combined with a carrier wave (e.g., millimeter-wave carrier wave) generated by a local oscillator 1012 at frequency mixer 1010.Frequency mixer 1010 can use heterodyning techniques or other frequency shifting techniques to frequency shift the output signals from communications interface 1008.For example, signals sent to and from the communications interface 1008 can be modulated signals such as orthogonal frequency division multiplexed (OFDM) signals formatted in accordance with a Long-Term Evolution (LTE) wireless protocol or other wireless 3G, 4G, 5G or higher voice and data protocol, a Zigbee, WIMAX, UltraWideband or IEEE 802.11 wireless protocol; a wired protocol such as an Ethernet protocol, universal serial bus (USB) protocol, a data over cable service interface specification (DOCSIS) protocol, a digital subscriber line (DSL) protocol, a Firewire (IEEE 1394) protocol or other wired or wireless protocol.","In an example embodiment, this frequency conversion can be done in the analog domain, and as a result, the frequency shifting can be done without regard to the type of communications protocol used by a base station, mobile devices, or in-building devices.","As new communications technologies are developed, the communications interface 1008 can be upgraded (e.g., updated with software, firmware, and/or hardware) or replaced and the frequency shifting and transmission apparatus can remain, simplifying upgrades.","The carrier wave can then be sent to a power amplifier (“PA”) 1014 and can be transmitted via the transmitter receiver device 1006 via the diplexer 1016.Signals received from the transmitter/receiver device 1006 that are directed towards the communications interface 1008 can be separated from other signals via diplexer 1016.The received signal can then be sent to low noise amplifier (“LNA”) 1018 for amplification.","A frequency mixer 1020, with help from local oscillator 1012 can downshift the received signal (which is in the millimeter-wave band or around 38 GHz in some embodiments) to the native frequency.","The communications interface 1008 can then receive the transmission at an input port (Rx).","In an embodiment, transmitter/receiver device 1006 can include a cylindrical or non-cylindrical metal (which, for example, can be hollow in an embodiment, but not necessarily drawn to scale) or other conducting or non-conducting waveguide and an end of the stub coupler 1002 can be placed in or in proximity to the waveguide or the transmitter/receiver device 1006 such that when the transmitter/receiver device 1006 generates a transmission, the guided wave couples to stub coupler 1002 and propagates as a guided wave 1004 about the waveguide surface of the stub coupler 1002.In some embodiments, the guided wave 1004 can propagate in part on the outer surface of the stub coupler 1002 and in part inside the stub coupler 1002.In other embodiments, the guided wave 1004 can propagate substantially or completely on the outer surface of the stub coupler 1002.In yet other embodiments, the guided wave 1004 can propagate substantially or completely inside the stub coupler 1002.In this latter embodiment, the guided wave 1004 can radiate at an end of the stub coupler 1002 (such as the tapered end shown in FIG.","4) for coupling to a transmission medium such as a wire 702 of FIG.","7.Similarly, if guided wave 1004 is incoming (coupled to the stub coupler 1002 from a wire 702), guided wave 1004 then enters the transmitter/receiver device 1006 and couples to the cylindrical waveguide or conducting waveguide.","While transmitter/receiver device 1006 is shown to include a separate waveguide—an antenna, cavity resonator, klystron, magnetron, travelling wave tube, or other radiating element can be employed to induce a guided wave on the coupler 1002, with or without the separate waveguide.","In an embodiment, stub coupler 1002 can be wholly constructed of a dielectric material (or another suitable insulating material), without any metallic or otherwise conducting materials therein.","Stub coupler 1002 can be composed of nylon, Teflon, polyethylene, a polyamide, other plastics, or other materials that are non-conducting and suitable for facilitating transmission of electromagnetic waves at least in part on an outer surface of such materials.","In another embodiment, stub coupler 1002 can include a core that is conducting/metallic, and have an exterior dielectric surface.","Similarly, a transmission medium that couples to the stub coupler 1002 for propagating electromagnetic waves induced by the stub coupler 1002 or for supplying electromagnetic waves to the stub coupler 1002 can, in addition to being a bare or insulated wire, be wholly constructed of a dielectric material (or another suitable insulating material), without any metallic or otherwise conducting materials therein.","It is noted that although FIG.","10A shows that the opening of transmitter receiver device 1006 is much wider than the stub coupler 1002, this is not to scale, and that in other embodiments the width of the stub coupler 1002 is comparable or slightly smaller than the opening of the hollow waveguide.","It is also not shown, but in an embodiment, an end of the coupler 1002 that is inserted into the transmitter/receiver device 1006 tapers down in order to reduce reflection and increase coupling efficiencies.","Before coupling to the stub coupler 1002, the one or more waveguide modes of the guided wave generated by the transmitter/receiver device 1006 can couple to the stub coupler 1002 to induce one or more wave propagation modes of the guided wave 1004.The wave propagation modes of the guided wave 1004 can be different than the hollow metal waveguide modes due to the different characteristics of the hollow metal waveguide and the dielectric waveguide.","For instance, wave propagation modes of the guided wave 1004 can comprise the fundamental transverse electromagnetic mode (Quasi-TEM00), where only small electrical and/or magnetic fields extend in the direction of propagation, and the electric and magnetic fields extend radially outwards from the stub coupler 1002 while the guided waves propagate along the stub coupler 1002.The fundamental transverse electromagnetic mode wave propagation mode may or may not exist inside a waveguide that is hollow.","Therefore, the hollow metal waveguide modes that are used by transmitter/receiver device 1006 are waveguide modes that can couple effectively and efficiently to wave propagation modes of stub coupler 1002.It will be appreciated that other constructs or combinations of the transmitter/receiver device 1006 and stub coupler 1002 are possible.","For example, a stub coupler 1002′ can be placed tangentially or in parallel (with or without a gap) with respect to an outer surface of the hollow metal waveguide of the transmitter/receiver device 1006′ (corresponding circuitry not shown) as depicted by reference 1000′ of FIG.","10B.","In another embodiment, not shown by reference 1000′, the stub coupler 1002′ can be placed inside the hollow metal waveguide of the transmitter/receiver device 1006′ without an axis of the stub coupler 1002′ being coaxially aligned with an axis of the hollow metal waveguide of the transmitter/receiver device 1006′.","In either of these embodiments, the guided wave generated by the transmitter/receiver device 1006′ can couple to a surface of the stub coupler 1002′ to induce one or more wave propagation modes of the guided wave 1004′ on the stub coupler 1002′ including a fundamental mode (e.g., a symmetric mode) and/or a non-fundamental mode (e.g., asymmetric mode).","In one embodiment, the guided wave 1004′ can propagate in part on the outer surface of the stub coupler 1002′ and in part inside the stub coupler 1002′.","In another embodiment, the guided wave 1004′ can propagate substantially or completely on the outer surface of the stub coupler 1002′.","In yet other embodiments, the guided wave 1004′ can propagate substantially or completely inside the stub coupler 1002′.","In this latter embodiment, the guided wave 1004′ can radiate at an end of the stub coupler 1002′ (such as the tapered end shown in FIG.","9) for coupling to a transmission medium such as a wire 702 of FIG.","9.It will be further appreciated that other constructs the transmitter/receiver device 1006 are possible.","For example, a hollow metal waveguide of a transmitter/receiver device 1006″ (corresponding circuitry not shown), depicted in FIG.","10B as reference 1000″, can be placed tangentially or in parallel (with or without a gap) with respect to an outer surface of a transmission medium such as the wire 702 of FIG.","4 without the use of the stub coupler 1002.In this embodiment, the guided wave generated by the transmitter/receiver device 1006″ can couple to a surface of the wire 702 to induce one or more wave propagation modes of a guided wave 908 on the wire 702 including a fundamental mode (e.g., a symmetric mode) and/or a non-fundamental mode (e.g., asymmetric mode).","In another embodiment, the wire 702 can be positioned inside a hollow metal waveguide of a transmitter/receiver device 1006′ (corresponding circuitry not shown) so that an axis of the wire 702 is coaxially (or not coaxially) aligned with an axis of the hollow metal waveguide without the use of the stub coupler 1002—see FIG.","10B reference 1000′″.","In this embodiment, the guided wave generated by the transmitter/receiver device 1006′″ can couple to a surface of the wire 702 to induce one or more wave propagation modes of a guided wave 908 on the wire including a fundamental mode (e.g., a symmetric mode) and/or a non-fundamental mode (e.g., asymmetric mode).","In the embodiments of 1000″ and 1000′″, for a wire 702 having an insulated outer surface, the guided wave 908 can propagate in part on the outer surface of the insulator and in part inside the insulator.","In embodiments, the guided wave 908 can propagate substantially or completely on the outer surface of the insulator, or substantially or completely inside the insulator.","In the embodiments of 1000″ and 1000′″, for a wire 702 that is a bare conductor, the guided wave 908 can propagate in part on the outer surface of the conductor and in part inside the conductor.","In another embodiment, the guided wave 908 can propagate substantially or completely on the outer surface of the conductor.","Referring now to FIG.","11, a block diagram 1100 illustrating an example, non-limiting embodiment of a dual stub coupler is shown.","In particular, a dual coupler design is presented for use in a transmission device, such as transmission device 101 or 102 presented in conjunction with FIG.","1.In an embodiment, two or more couplers (such as the stub couplers 1104 and 1106) can be positioned around a wire 1102 in order to receive guided wave 1108.In an embodiment, one coupler is enough to receive the guided wave 1108.In that case, guided wave 1108 couples to coupler 1104 and propagates as guided wave 1110.If the field structure of the guided wave 1108 oscillates or undulates around the wire 1102 due to the particular guided wave mode(s) or various outside factors, then coupler 1106 can be placed such that guided wave 1108 couples to coupler 1106.In some embodiments, four or more couplers can be placed around a portion of the wire 1102, e.g., at 90 degrees or another spacing with respect to each other, in order to receive guided waves that may oscillate or rotate around the wire 1102, that have been induced at different azimuthal orientations or that have non-fundamental or higher order modes that, for example, have lobes and/or nulls or other asymmetries that are orientation dependent.","However, it will be appreciated that there may be less than or more than four couplers placed around a portion of the wire 1102 without departing from example embodiments.","It should be noted that while couplers 1106 and 1104 are illustrated as stub couplers, any other of the coupler designs described herein including arc couplers, antenna or horn couplers, magnetic couplers, etc., could likewise be used.","It will also be appreciated that while some example embodiments have presented a plurality of couplers around at least a portion of a wire 1102, this plurality of couplers can also be considered as part of a single coupler system having multiple coupler subcomponents.","For example, two or more couplers can be manufactured as single system that can be installed around a wire in a single installation such that the couplers are either pre-positioned or adjustable relative to each other (either manually or automatically with a controllable mechanism such as a motor or other actuator) in accordance with the single system.","Receivers coupled to couplers 1106 and 1104 can use diversity combining to combine signals received from both couplers 1106 and 1104 in order to maximize the signal quality.","In other embodiments, if one or the other of the couplers 1104 and 1106 receive a transmission that is above a predetermined threshold, receivers can use selection diversity when deciding which signal to use.","Further, while reception by a plurality of couplers 1106 and 1104 is illustrated, transmission by couplers 1106 and 1104 in the same configuration can likewise take place.","In particular, a wide range of multi-input multi-output (MIMO) transmission and reception techniques can be employed for transmissions where a transmission device, such as transmission device 101 or 102 presented in conjunction with FIG.","1 includes multiple transceivers and multiple couplers.","It is noted that the graphical representations of waves 1108 and 1110 are presented merely to illustrate the principles that guided wave 1108 induces or otherwise launches a wave 1110 on a coupler 1104.The actual electric and magnetic fields generated as a result of such wave propagation may vary depending on the frequencies employed, the design of the coupler 1104, the dimensions and composition of the wire 1102, as well as its surface characteristics, its insulation if any, the electromagnetic properties of the surrounding environment, etc.","Referring now to FIG.","12, a block diagram 1200 illustrating an example, non-limiting embodiment of a repeater system is shown.","In particular, a repeater device 1210 is presented for use in a transmission device, such as transmission device 101 or 102 presented in conjunction with FIG.","1.In this system, two couplers 1204 and 1214 can be placed near a wire 1202 or other transmission medium such that guided waves 1205 propagating along the wire 1202 are extracted by coupler 1204 as wave 1206 (e.g.","as a guided wave), and then are boosted or repeated by repeater device 1210 and launched as a wave 1216 (e.g.","as a guided wave) onto coupler 1214.The wave 1216 can then be launched on the wire 1202 and continue to propagate along the wire 1202 as a guided wave 1217.In an embodiment, the repeater device 1210 can receive at least a portion of the power utilized for boosting or repeating through magnetic coupling with the wire 1202, for example, when the wire 1202 is a power line or otherwise contains a power-carrying conductor.","It should be noted that while couplers 1204 and 1214 are illustrated as stub couplers, any other of the coupler designs described herein including arc couplers, antenna or horn couplers, magnetic couplers, or the like, could likewise be used.","In some embodiments, repeater device 1210 can repeat the transmission associated with wave 1206, and in other embodiments, repeater device 1210 can include a communications interface 205 that extracts data or other signals from the wave 1206 for supplying such data or signals to another network and/or one or more other devices as communication signals 110 or 112 and/or receiving communication signals 110 or 112 from another network and/or one or more other devices and launch guided wave 1216 having embedded therein the received communication signals 110 or 112.In a repeater configuration, receiver waveguide 1208 can receive the wave 1206 from the coupler 1204 and transmitter waveguide 1212 can launch guided wave 1216 onto coupler 1214 as guided wave 1217.Between receiver waveguide 1208 and transmitter waveguide 1212, the signal embedded in guided wave 1206 and/or the guided wave 1216 itself can be amplified to correct for signal loss and other inefficiencies associated with guided wave communications or the signal can be received and processed to extract the data contained therein and regenerated for transmission.","In an embodiment, the receiver waveguide 1208 can be configured to extract data from the signal, process the data to correct for data errors utilizing for example error correcting codes, and regenerate an updated signal with the corrected data.","The transmitter waveguide 1212 can then transmit guided wave 1216 with the updated signal embedded therein.","In an embodiment, a signal embedded in guided wave 1206 can be extracted from the transmission and processed for communication with another network and/or one or more other devices via communications interface 205 as communication signals 110 or 112.Similarly, communication signals 110 or 112 received by the communications interface 205 can be inserted into a transmission of guided wave 1216 that is generated and launched onto coupler 1214 by transmitter waveguide 1212.It is noted that although FIG.","12 shows guided wave transmissions 1206 and 1216 entering from the left and exiting to the right respectively, this is merely a simplification and is not intended to be limiting.","In other embodiments, receiver waveguide 1208 and transmitter waveguide 1212 can also function as transmitters and receivers respectively, allowing the repeater device 1210 to be bi-directional.","In an embodiment, repeater device 1210 can be placed at locations where there are discontinuities or obstacles on the wire 1202 or other transmission medium.","In the case where the wire 1202 is a power line, these obstacles can include transformers, connections, utility poles, and other such power line devices.","The repeater device 1210 can help the guided (e.g., surface) waves jump over these obstacles on the line and boost the transmission power at the same time.","In other embodiments, a coupler can be used to jump over the obstacle without the use of a repeater device.","In that embodiment, both ends of the coupler can be tied or fastened to the wire, thus providing a path for the guided wave to travel without being blocked by the obstacle.","Turning now to FIG.","13, illustrated is a block diagram 1300 of an example, non-limiting embodiment of a bidirectional repeater in accordance with various aspects described herein.","In particular, a bidirectional repeater device 1306 is presented for use in a transmission device, such as transmission device 101 or 102 presented in conjunction with FIG.","1.It should be noted that while the couplers are illustrated as stub couplers, any other of the coupler designs described herein including arc couplers, antenna or horn couplers, magnetic couplers, or the like, could likewise be used.","The bidirectional repeater 1306 can employ diversity paths in the case of when two or more wires or other transmission media are present.","Since guided wave transmissions have different transmission efficiencies and coupling efficiencies for transmission medium of different types such as insulated wires, un-insulated wires or other types of transmission media and further, if exposed to the elements, can be affected by weather, and other atmospheric conditions, it can be advantageous to selectively transmit on different transmission media at certain times.","In various embodiments, the various transmission media can be designated as a primary, secondary, tertiary, etc.","whether or not such designation indicates a preference of one transmission medium over another.","In the embodiment shown, the transmission media include an insulated or uninsulated wire 1302 and an insulated or uninsulated wire 1304 (referred to herein as wires 1302 and 1304, respectively).","The repeater device 1306 uses a receiver coupler 1308 to receive a guided wave traveling along wire 1302 and repeats the transmission using transmitter waveguide 1310 as a guided wave along wire 1304.In other embodiments, repeater device 1306 can switch from the wire 1304 to the wire 1302, or can repeat the transmissions along the same paths.","Repeater device 1306 can include sensors, or be in communication with sensors (or a network management system 1601 depicted in FIG.","16A) that indicate conditions that can affect the transmission.","Based on the feedback received from the sensors, the repeater device 1306 can make the determination about whether to keep the transmission along the same wire, or transfer the transmission to the other wire.","Turning now to FIG.","14, illustrated is a block diagram 1400 illustrating an example, non-limiting embodiment of a bidirectional repeater system.","In particular, a bidirectional repeater system is presented for use in a transmission device, such as transmission device 101 or 102 presented in conjunction with FIG.","1.The bidirectional repeater system includes waveguide coupling devices 1402 and 1404 that receive and transmit transmissions from other coupling devices located in a distributed antenna system or backhaul system.","In various embodiments, waveguide coupling device 1402 can receive a transmission from another waveguide coupling device, wherein the transmission has a plurality of subcarriers.","Diplexer 1406 can separate the transmission from other transmissions, and direct the transmission to low-noise amplifier (“LNA”) 1408.A frequency mixer 1428, with help from a local oscillator 1412, can downshift the transmission (which is in the millimeter-wave band or around 38 GHz in some embodiments) to a lower frequency, such as a cellular band (˜1.9 GHz) for a distributed antenna system, a native frequency, or other frequency for a backhaul system.","An extractor (or demultiplexer) 1432 can extract the signal on a subcarrier and direct the signal to an output component 1422 for optional amplification, buffering or isolation by power amplifier 1424 for coupling to communications interface 205.The communications interface 205 can further process the signals received from the power amplifier 1424 or otherwise transmit such signals over a wireless or wired interface to other devices such as a base station, mobile devices, a building, etc.","For the signals that are not being extracted at this location, extractor 1432 can redirect them to another frequency mixer 1436, where the signals are used to modulate a carrier wave generated by local oscillator 1414.The carrier wave, with its subcarriers, is directed to a power amplifier (“PA”) 1416 and is retransmitted by waveguide coupling device 1404 to another system, via diplexer 1420.An LNA 1426 can be used to amplify, buffer or isolate signals that are received by the communication interface 205 and then send the signal to a multiplexer 1434 which merges the signal with signals that have been received from waveguide coupling device 1404.The signals received from coupling device 1404 have been split by diplexer 1420, and then passed through LNA 1418, and downshifted in frequency by frequency mixer 1438.When the signals are combined by multiplexer 1434, they are upshifted in frequency by frequency mixer 1430, and then boosted by PA 1410, and transmitted to another system by waveguide coupling device 1402.In an embodiment bidirectional repeater system can be merely a repeater without the output device 1422.In this embodiment, the multiplexer 1434 would not be utilized and signals from LNA 1418 would be directed to mixer 1430 as previously described.","It will be appreciated that in some embodiments, the bidirectional repeater system could also be implemented using two distinct and separate unidirectional repeaters.","In an alternative embodiment, a bidirectional repeater system could also be a booster or otherwise perform retransmissions without downshifting and upshifting.","Indeed in example embodiment, the retransmissions can be based upon receiving a signal or guided wave and performing some signal or guided wave processing or reshaping, filtering, and/or amplification, prior to retransmission of the signal or guided wave.","Referring now to FIG.","15, a block diagram 1500 illustrating an example, non-limiting embodiment of a guided wave communications system is shown.","This diagram depicts an exemplary environment in which a guided wave communication system, such as the guided wave communication system presented in conjunction with FIG.","1, can be used.","To provide network connectivity to additional base station devices, a backhaul network that links the communication cells (e.g., macrocells and macrocells) to network devices of a core network correspondingly expands.","Similarly, to provide network connectivity to a distributed antenna system, an extended communication system that links base station devices and their distributed antennas is desirable.","A guided wave communication system 1500 such as shown in FIG.","15 can be provided to enable alternative, increased or additional network connectivity and a waveguide coupling system can be provided to transmit and/or receive guided wave (e.g., surface wave) communications on a transmission medium such as a wire that operates as a single-wire transmission line (e.g., a utility line), and that can be used as a waveguide and/or that otherwise operates to guide the transmission of an electromagnetic wave.","The guided wave communication system 1500 can comprise a first instance of a distribution system 1550 that includes one or more base station devices (e.g., base station device 1504) that are communicably coupled to a central office 1501 and/or a macrocell site 1502.Base station device 1504 can be connected by a wired (e.g., fiber and/or cable), or by a wireless (e.g., microwave wireless) connection to the macrocell site 1502 and the central office 1501.A second instance of the distribution system 1560 can be used to provide wireless voice and data services to mobile device 1522 and to residential and/or commercial establishments 1542 (herein referred to as establishments 1542).","System 1500 can have additional instances of the distribution systems 1550 and 1560 for providing voice and/or data services to mobile devices 1522-1524 and establishments 1542 as shown in FIG.","15.Macrocells such as macrocell site 1502 can have dedicated connections to a mobile network and base station device 1504 or can share and/or otherwise use another connection.","Central office 1501 can be used to distribute media content and/or provide internet service provider (ISP) services to mobile devices 1522-1524 and establishments 1542.The central office 1501 can receive media content from a constellation of satellites 1530 (one of which is shown in FIG.","15) or other sources of content, and distribute such content to mobile devices 1522-1524 and establishments 1542 via the first and second instances of the distribution system 1550 and 1560.The central office 1501 can also be communicatively coupled to the Internet 1503 for providing internet data services to mobile devices 1522-1524 and establishments 1542.Base station device 1504 can be mounted on, or attached to, utility pole 1516.In other embodiments, base station device 1504 can be near transformers and/or other locations situated nearby a power line.","Base station device 1504 can facilitate connectivity to a mobile network for mobile devices 1522 and 1524.Antennas 1512 and 1514, mounted on or near utility poles 1518 and 1520, respectively, can receive signals from base station device 1504 and transmit those signals to mobile devices 1522 and 1524 over a much wider area than if the antennas 1512 and 1514 were located at or near base station device 1504.It is noted that FIG.","15 displays three utility poles, in each instance of the distribution systems 1550 and 1560, with one base station device, for purposes of simplicity.","In other embodiments, utility pole 1516 can have more base station devices, and more utility poles with distributed antennas and/or tethered connections to establishments 1542.A transmission device 1506, such as transmission device 101 or 102 presented in conjunction with FIG.","1, can transmit a signal from base station device 1504 to antennas 1512 and 1514 via utility or power line(s) that connect the utility poles 1516, 1518, and 1520.To transmit the signal, radio source and/or transmission device 1506 upconverts the signal (e.g., via frequency mixing) from base station device 1504 or otherwise converts the signal from the base station device 1504 to a microwave band signal and the transmission device 1506 launches a microwave band wave that propagates as a guided wave traveling along the utility line or other wire as described in previous embodiments.","At utility pole 1518, another transmission device 1508 receives the guided wave (and optionally can amplify it as needed or desired or operate as a repeater to receive it and regenerate it) and sends it forward as a guided wave on the utility line or other wire.","The transmission device 1508 can also extract a signal from the microwave band guided wave and shift it down in frequency or otherwise convert it to its original cellular band frequency (e.g., 1.9 GHz or other defined cellular frequency) or another cellular (or non-cellular) band frequency.","An antenna 1512 can wireless transmit the downshifted signal to mobile device 1522.The process can be repeated by transmission device 1510, antenna 1514 and mobile device 1524, as necessary or desirable.","Transmissions from mobile devices 1522 and 1524 can also be received by antennas 1512 and 1514 respectively.","The transmission devices 1508 and 1510 can upshift or otherwise convert the cellular band signals to microwave band and transmit the signals as guided wave (e.g., surface wave or other electromagnetic wave) transmissions over the power line(s) to base station device 1504.Media content received by the central office 1501 can be supplied to the second instance of the distribution system 1560 via the base station device 1504 for distribution to mobile devices 1522 and establishments 1542.The transmission device 1510 can be tethered to the establishments 1542 by one or more wired connections or a wireless interface.","The one or more wired connections may include without limitation, a power line, a coaxial cable, a fiber cable, a twisted pair cable, a guided wave transmission medium or other suitable wired mediums for distribution of media content and/or for providing internet services.","In an example embodiment, the wired connections from the transmission device 1510 can be communicatively coupled to one or more very high bit rate digital subscriber line (VDSL) modems located at one or more corresponding service area interfaces (SAIs—not shown) or pedestals, each SAI or pedestal providing services to a portion of the establishments 1542.The VDSL modems can be used to selectively distribute media content and/or provide internet services to gateways (not shown) located in the establishments 1542.The SAIs or pedestals can also be communicatively coupled to the establishments 1542 over a wired medium such as a power line, a coaxial cable, a fiber cable, a twisted pair cable, a guided wave transmission medium or other suitable wired mediums.","In other example embodiments, the transmission device 1510 can be communicatively coupled directly to establishments 1542 without intermediate interfaces such as the SAIs or pedestals.","In another example embodiment, system 1500 can employ diversity paths, where two or more utility lines or other wires are strung between the utility poles 1516, 1518, and 1520 (e.g., for example, two or more wires between poles 1516 and 1520) and redundant transmissions from base station/macrocell site 1502 are transmitted as guided waves down the surface of the utility lines or other wires.","The utility lines or other wires can be either insulated or uninsulated, and depending on the environmental conditions that cause transmission losses, the coupling devices can selectively receive signals from the insulated or uninsulated utility lines or other wires.","The selection can be based on measurements of the signal-to-noise ratio of the wires, or based on determined weather/environmental conditions (e.g., moisture detectors, weather forecasts, etc.).","The use of diversity paths with system 1500 can enable alternate routing capabilities, load balancing, increased load handling, concurrent bi-directional or synchronous communications, spread spectrum communications, etc.","It is noted that the use of the transmission devices 1506, 1508, and 1510 in FIG.","15 are by way of example only, and that in other embodiments, other uses are possible.","For instance, transmission devices can be used in a backhaul communication system, providing network connectivity to base station devices.","Transmission devices 1506, 1508, and 1510 can be used in many circumstances where it is desirable to transmit guided wave communications over a wire, whether insulated or not insulated.","Transmission devices 1506, 1508, and 1510 are improvements over other coupling devices due to no contact or limited physical and/or electrical contact with the wires that may carry high voltages.","The transmission device can be located away from the wire (e.g., spaced apart from the wire) and/or located on the wire so long as it is not electrically in contact with the wire, as the dielectric acts as an insulator, allowing for cheap, easy, and/or less complex installation.","However, as previously noted conducting or non-dielectric couplers can be employed, for example in configurations where the wires correspond to a telephone network, cable television network, broadband data service, fiber optic communications system or other network employing low voltages or having insulated transmission lines.","It is further noted, that while base station device 1504 and macrocell site 1502 are illustrated in an embodiment, other network configurations are likewise possible.","For example, devices such as access points or other wireless gateways can be employed in a similar fashion to extend the reach of other networks such as a wireless local area network, a wireless personal area network or other wireless network that operates in accordance with a communication protocol such as a 802.11 protocol, WIMAX protocol, UltraWideband protocol, Bluetooth protocol, Zigbee protocol or other wireless protocol.","Referring now to FIGS.","16A, 16B and 16C, block diagrams illustrating an example, non-limiting embodiment of a system for managing a communication system are shown.","Considering FIG.","16A, a waveguide system 1602 is presented for use in a guided wave communications system, such as the system presented in conjunction with FIG.","15.The waveguide system 1602 can comprise sensors 1604, a power management system 1605, a transmission device 101 or 102 that includes at least one communication interface 205, transceiver 210 and coupler 220.The waveguide system 1602 can be coupled to a power line 1610 for facilitating guided wave communications in accordance with embodiments described in the subject disclosure.","In an example embodiment, the transmission device 101 or 102 includes coupler 220 for inducing electromagnetic waves on a surface of the power line 1610 that longitudinally propagate along the surface of the power line 1610 as described in the subject disclosure.","The transmission device 101 or 102 can also serve as a repeater for retransmitting electromagnetic waves on the same power line 1610 or for routing electromagnetic waves between power lines 1610 as shown in FIGS.","12-13.The transmission device 101 or 102 includes transceiver 210 configured to, for example, up-convert a signal operating at an original frequency range to electromagnetic waves operating at, exhibiting, or associated with a carrier frequency that propagate along a coupler to induce corresponding guided electromagnetic waves that propagate along a surface of the power line 1610.A carrier frequency can be represented by a center frequency having upper and lower cutoff frequencies that define the bandwidth of the electromagnetic waves.","The power line 1610 can be a wire (e.g., single stranded or multi-stranded) having a conducting surface or insulated surface.","The transceiver 210 can also receive signals from the coupler 220 and down-convert the electromagnetic waves operating at a carrier frequency to signals at their original frequency.","Signals received by the communications interface 205 of transmission device 101 or 102 for up-conversion can include without limitation signals supplied by a central office 1611 over a wired or wireless interface of the communications interface 205, a base station 1614 over a wired or wireless interface of the communications interface 205, wireless signals transmitted by mobile devices 1620 to the base station 1614 for delivery over the wired or wireless interface of the communications interface 205, signals supplied by in-building communication devices 1618 over the wired or wireless interface of the communications interface 205, and/or wireless signals supplied to the communications interface 205 by mobile devices 1612 roaming in a wireless communication range of the communications interface 205.In embodiments where the waveguide system 1602 functions as a repeater, such as shown in FIGS.","12-13, the communications interface 205 may or may not be included in the waveguide system 1602.The electromagnetic waves propagating along the surface of the power line 1610 can be modulated and formatted to include packets or frames of data that include a data payload and further include networking information (such as header information for identifying one or more destination waveguide systems 1602).","The networking information may be provided by the waveguide system 1602 or an originating device such as the central office 1611, the base station 1614, mobile devices 1620, or in-building devices 1618, or a combination thereof.","Additionally, the modulated electromagnetic waves can include error correction data for mitigating signal disturbances.","The networking information and error correction data can be used by a destination waveguide system 1602 for detecting transmissions directed to it, and for down-converting and processing with error correction data transmissions that include voice and/or data signals directed to recipient communication devices communicatively coupled to the destination waveguide system 1602.Referring now to the sensors 1604 of the waveguide system 1602, the sensors 1604 can comprise one or more of a temperature sensor 1604a, a disturbance detection sensor 1604b, a loss of energy sensor 1604c, a noise sensor 1604d, a vibration sensor 1604e, an environmental (e.g., weather) sensor 1604f, and/or an image sensor 1604g.","The temperature sensor 1604a can be used to measure ambient temperature, a temperature of the transmission device 101 or 102, a temperature of the power line 1610, temperature differentials (e.g., compared to a setpoint or baseline, between transmission device 101 or 102 and 1610, etc.","), or any combination thereof.","In one embodiment, temperature metrics can be collected and reported periodically to a network management system 1601 by way of the base station 1614.The disturbance detection sensor 1604b can perform measurements on the power line 1610 to detect disturbances such as signal reflections, which may indicate a presence of a downstream disturbance that may impede the propagation of electromagnetic waves on the power line 1610.A signal reflection can represent a distortion resulting from, for example, an electromagnetic wave transmitted on the power line 1610 by the transmission device 101 or 102 that reflects in whole or in part back to the transmission device 101 or 102 from a disturbance in the power line 1610 located downstream from the transmission device 101 or 102.Signal reflections can be caused by obstructions on the power line 1610.For example, a tree limb may cause electromagnetic wave reflections when the tree limb is lying on the power line 1610, or is in close proximity to the power line 1610 which may cause a corona discharge.","Other obstructions that can cause electromagnetic wave reflections can include without limitation an object that has been entangled on the power line 1610 (e.g., clothing, a shoe wrapped around a power line 1610 with a shoe string, etc.","), a corroded build-up on the power line 1610 or an ice build-up.","Power grid components may also impede or obstruct with the propagation of electromagnetic waves on the surface of power lines 1610.Illustrations of power grid components that may cause signal reflections include without limitation a transformer and a joint for connecting spliced power lines.","A sharp angle on the power line 1610 may also cause electromagnetic wave reflections.","The disturbance detection sensor 1604b can comprise a circuit to compare magnitudes of electromagnetic wave reflections to magnitudes of original electromagnetic waves transmitted by the transmission device 101 or 102 to determine how much a downstream disturbance in the power line 1610 attenuates transmissions.","The disturbance detection sensor 1604b can further comprise a spectral analyzer circuit for performing spectral analysis on the reflected waves.","The spectral data generated by the spectral analyzer circuit can be compared with spectral profiles via pattern recognition, an expert system, curve fitting, matched filtering or other artificial intelligence, classification or comparison technique to identify a type of disturbance based on, for example, the spectral profile that most closely matches the spectral data.","The spectral profiles can be stored in a memory of the disturbance detection sensor 1604b or may be remotely accessible by the disturbance detection sensor 1604b.","The profiles can comprise spectral data that models different disturbances that may be encountered on power lines 1610 to enable the disturbance detection sensor 1604b to identify disturbances locally.","An identification of the disturbance if known can be reported to the network management system 1601 by way of the base station 1614.The disturbance detection sensor 1604b can also utilize the transmission device 101 or 102 to transmit electromagnetic waves as test signals to determine a roundtrip time for an electromagnetic wave reflection.","The round trip time measured by the disturbance detection sensor 1604b can be used to calculate a distance traveled by the electromagnetic wave up to a point where the reflection takes place, which enables the disturbance detection sensor 1604b to calculate a distance from the transmission device 101 or 102 to the downstream disturbance on the power line 1610.The distance calculated can be reported to the network management system 1601 by way of the base station 1614.In one embodiment, the location of the waveguide system 1602 on the power line 1610 may be known to the network management system 1601, which the network management system 1601 can use to determine a location of the disturbance on the power line 1610 based on a known topology of the power grid.","In another embodiment, the waveguide system 1602 can provide its location to the network management system 1601 to assist in the determination of the location of the disturbance on the power line 1610.The location of the waveguide system 1602 can be obtained by the waveguide system 1602 from a pre-programmed location of the waveguide system 1602 stored in a memory of the waveguide system 1602, or the waveguide system 1602 can determine its location using a GPS receiver (not shown) included in the waveguide system 1602.The power management system 1605 provides energy to the aforementioned components of the waveguide system 1602.The power management system 1605 can receive energy from solar cells, or from a transformer (not shown) coupled to the power line 1610, or by inductive coupling to the power line 1610 or another nearby power line.","The power management system 1605 can also include a backup battery and/or a super capacitor or other capacitor circuit for providing the waveguide system 1602 with temporary power.","The loss of energy sensor 1604c can be used to detect when the waveguide system 1602 has a loss of power condition and/or the occurrence of some other malfunction.","For example, the loss of energy sensor 1604c can detect when there is a loss of power due to defective solar cells, an obstruction on the solar cells that causes them to malfunction, loss of power on the power line 1610, and/or when the backup power system malfunctions due to expiration of a backup battery, or a detectable defect in a super capacitor.","When a malfunction and/or loss of power occurs, the loss of energy sensor 1604c can notify the network management system 1601 by way of the base station 1614.The noise sensor 1604d can be used to measure noise on the power line 1610 that may adversely affect transmission of electromagnetic waves on the power line 1610.The noise sensor 1604d can sense unexpected electromagnetic interference, noise bursts, or other sources of disturbances that may interrupt reception of modulated electromagnetic waves on a surface of a power line 1610.A noise burst can be caused by, for example, a corona discharge, or other source of noise.","The noise sensor 1604d can compare the measured noise to a noise profile obtained by the waveguide system 1602 from an internal database of noise profiles or from a remotely located database that stores noise profiles via pattern recognition, an expert system, curve fitting, matched filtering or other artificial intelligence, classification or comparison technique.","From the comparison, the noise sensor 1604d may identify a noise source (e.g., corona discharge or otherwise) based on, for example, the noise profile that provides the closest match to the measured noise.","The noise sensor 1604d can also detect how noise affects transmissions by measuring transmission metrics such as bit error rate, packet loss rate, jitter, packet retransmission requests, etc.","The noise sensor 1604d can report to the network management system 1601 by way of the base station 1614 the identity of noise sources, their time of occurrence, and transmission metrics, among other things.","The vibration sensor 1604e can include accelerometers and/or gyroscopes to detect 2D or 3D vibrations on the power line 1610.The vibrations can be compared to vibration profiles that can be stored locally in the waveguide system 1602, or obtained by the waveguide system 1602 from a remote database via pattern recognition, an expert system, curve fitting, matched filtering or other artificial intelligence, classification or comparison technique.","Vibration profiles can be used, for example, to distinguish fallen trees from wind gusts based on, for example, the vibration profile that provides the closest match to the measured vibrations.","The results of this analysis can be reported by the vibration sensor 1604e to the network management system 1601 by way of the base station 1614.The environmental sensor 1604f can include a barometer for measuring atmospheric pressure, ambient temperature (which can be provided by the temperature sensor 1604a), wind speed, humidity, wind direction, and rainfall, among other things.","The environmental sensor 1604f can collect raw information and process this information by comparing it to environmental profiles that can be obtained from a memory of the waveguide system 1602 or a remote database to predict weather conditions before they arise via pattern recognition, an expert system, knowledge-based system or other artificial intelligence, classification or other weather modeling and prediction technique.","The environmental sensor 1604f can report raw data as well as its analysis to the network management system 1601.The image sensor 1604g can be a digital camera (e.g., a charged coupled device or CCD imager, infrared camera, etc.)","for capturing images in a vicinity of the waveguide system 1602.The image sensor 1604g can include an electromechanical mechanism to control movement (e.g., actual position or focal points/zooms) of the camera for inspecting the power line 1610 from multiple perspectives (e.g., top surface, bottom surface, left surface, right surface and so on).","Alternatively, the image sensor 1604g can be designed such that no electromechanical mechanism is needed in order to obtain the multiple perspectives.","The collection and retrieval of imaging data generated by the image sensor 1604g can be controlled by the network management system 1601, or can be autonomously collected and reported by the image sensor 1604g to the network management system 1601.Other sensors that may be suitable for collecting telemetry information associated with the waveguide system 1602 and/or the power lines 1610 for purposes of detecting, predicting and/or mitigating disturbances that can impede the propagation of electromagnetic wave transmissions on power lines 1610 (or any other form of a transmission medium of electromagnetic waves) may be utilized by the waveguide system 1602.To mitigate harsh winter conditions, the waveguide system 1602 of FIG.","16A can be adapted to use a heater system 1630 such as depicted in FIG.","16B.","The heater system 1630 can comprise a toroidal inductor 1631 that surrounds a cross-sectional view of a transmission medium 1633, such as the power line 1610 shown in FIG.","16A.","The toroidal inductor 1631 can be constructed of multiple turns of wire 1636 wrapped around an annular toroid of powdered iron or other ferrite (referred to herein, for illustration purposes, as a ferrite core 1637).","In an embodiment where the transmission medium 1633 is a bare wire, a dielectric washer or other insulator 1635 can provide electrical insulation while supporting the wire within the toroidal inductor 1631.Such a dielectric washer can be constructed of Teflon, polystyrene, polyethylene or other dielectric or insulating material.","In cases where the transmission medium 1633 is nonconductive or includes an insulating sheath or jacket, the dielectric washer can be eliminated.","A power signal conducted by the transmission medium 1633 (e.g., 60 Hz or 50 Hz medium voltage power signal) can induce currents in the wire 1636 wrapped around the ferrite core 1637.The current induced in the wire 1636 can feed a heating element (e.g., a resistor) 1632.To control activation of the heating element 1632, the heating element 1632 can include a controllable switch (not shown) that can be opened to break the circuit formed by the wire 1636 and the heating element 1632, and thereby disable the heating element 1632.When the switch is closed and current begins to flow in the circuit, the heating element 1632 is enabled and thereby emits heat.","In one embodiment, the waveguide system 1602 of FIG.","16A can utilize the temperature sensor 1604a to measure an internal temperature of the waveguide system 1602 and/or an ambient temperature in a vicinity of the waveguide system 1602.In an embodiment, the waveguide system 1602 can use the image sensor 1604g singly or in combination with the temperature sensor 1604a.","The image sensor 1604g can be used to determine if ice and/or snow is accumulating on an outer surface of the waveguide system 1602.To place the toroidal inductor 1631 on a transmission medium 1633, such as a power line, the toroidal inductor 1631 can be inserted into the transmission medium 1633 through a middle cavity opening of the toroidal inductor 1631 if the power line has an open endpoint, or can be separated mechanically at the dashed lines 1639.In the latter embodiment, the toroidal inductor 1631 can be separated to enable placement on the transmission medium 1633 and reattached with a hinge, latch or other mechanical features during an installation process of the waveguide system 1602 on the power line.","Turning now to FIG.","16D, flow diagram of an example, non-limiting embodiment of a method 1670 in accordance with various aspects described herein is shown.","Method 1670 can begin with step 1672 where the waveguide system 1602 monitors the environment using the temperature sensor 1604a and/or the image sensor 1604g as described above.","It the waveguide system 1602 determines at step 1674 that the measured temperature (internal and/or ambient) falls below one or more thresholds (e.g., 32° F.) and/or images indicate there is an accumulation of ice and/or snow on a housing assembly of the waveguide system 1602, a circuit 1634 shown in FIG.","16B can generate at step 1676 a signal that causes the switch used by the heating element 1632 to close and thereby cause current to flow through the heating element 1632 to emit heat inside the waveguide system 1602.The circuit 1634 can be a controller (e.g., a microprocessor) of the waveguide system 1602.The heat emitted inside the housing assembly of the waveguide system 1602 can be used to prevent malfunction of circuits used by the waveguide system 1602 due to severe weather conditions.","Additionally, the heat emitted by the heating element 1632 may radiate sufficiently to heat the housing assembly of the waveguide system 1602 and thereby cause snow or ice to melt.","Once the waveguide system 1602 detects at steps 1672 that the temperature and/or snow or ice accumulation has dissipated, the waveguide system 1602 can proceed to step 1678 to disable the heating element 1632 by the circuit 1634 emitting a signal that causes the switch to open and break the circuit to prevent current flow in the heating element 1632.To maintain a steady temperature that prevents ice and/or snow accumulation, the steps of method 1670 can be adapted to operate as a thermostat that maintains a near constant temperature of the waveguide system 1602 to preemptively prevent snow and/or ice accumulation on the housing assembly of the waveguide system 1602.While for purposes of simplicity of explanation, the respective processes are shown and described as a series of blocks in FIG.","16D, it is to be understood and appreciated that the claimed subject matter is not limited by the order of the blocks, as some blocks may occur in different orders and/or concurrently with other blocks from what is depicted and described herein.","Moreover, not all illustrated blocks may be required to implement the methods described herein.","Referring now to FIG.","16C, block diagram 1650 illustrates an example, non-limiting embodiment of a system for managing a power grid 1653 and a communication system 1655 embedded therein or associated therewith in accordance with various aspects described herein.","The communication system 1655 comprises a plurality of waveguide systems 1602 coupled to power lines 1610 of the power grid 1653.At least a portion of the waveguide systems 1602 used in the communication system 1655 can be in direct communication with a base station 1614 and/or the network management system 1601.Waveguide systems 1602 not directly connected to a base station 1614 or the network management system 1601 can engage in communication sessions with either a base station 1614 or the network management system 1601 by way of other downstream waveguide systems 1602 connected to a base station 1614 or the network management system 1601.The network management system 1601 can be communicatively coupled to equipment of a utility company 1652 and equipment of a communications service provider 1654 for providing each entity, status information associated with the power grid 1653 and the communication system 1655, respectively.","The network management system 1601, the equipment of the utility company 1652, and the communications service provider 1654 can access communication devices utilized by utility company personnel 1656 and/or communication devices utilized by communications service provider personnel 1658 for purposes of providing status information and/or for directing such personnel in the management of the power grid 1653 and/or communication system 1655.FIG.","17A illustrates a flow diagram of an example, non-limiting embodiment of a method 1700 for detecting and mitigating disturbances occurring in a communication network of the systems of FIGS.","16A-16C.","Method 1700 can begin with step 1702 where a waveguide system 1602 transmits and receives messages embedded in, or forming part of, modulated electromagnetic waves or another type of electromagnetic waves traveling along a surface of a power line 1610.The messages can be voice messages, streaming video, and/or other data/information exchanged between communication devices communicatively coupled to the communication system 1655.At step 1704 the sensors 1604 of the waveguide system 1602 can collect sensing data.","In an embodiment, the sensing data can be collected in step 1704 prior to, during, or after the transmission and/or receipt of messages in step 1702.At step 1706 the waveguide system 1602 (or the sensors 1604 themselves) can determine from the sensing data an actual or predicted occurrence of a disturbance in the communication system 1655 that can affect communications originating from (e.g., transmitted by) or received by the waveguide system 1602.The waveguide system 1602 (or the sensors 1604) can process temperature data, signal reflection data, loss of energy data, noise data, vibration data, environmental data, or any combination thereof to make this determination.","The waveguide system 1602 (or the sensors 1604) may also detect, identify, estimate, or predict the source of the disturbance and/or its location in the communication system 1655.If a disturbance is neither detected/identified nor predicted/estimated at step 1708, the waveguide system 1602 can proceed to step 1702 where it continues to transmit and receive messages embedded in, or forming part of, modulated electromagnetic waves traveling along a surface of the power line 1610.If at step 1708 a disturbance is detected/identified or predicted/estimated to occur, the waveguide system 1602 proceeds to step 1710 to determine if the disturbance adversely affects (or alternatively, is likely to adversely affect or the extent to which it may adversely affect) transmission or reception of messages in the communication system 1655.In one embodiment, a duration threshold and a frequency of occurrence threshold can be used at step 1710 to determine when a disturbance adversely affects communications in the communication system 1655.For illustration purposes only, assume a duration threshold is set to 500 ms, while a frequency of occurrence threshold is set to 5 disturbances occurring in an observation period of 10 sec.","Thus, a disturbance having a duration greater than 500 ms will trigger the duration threshold.","Additionally, any disturbance occurring more than 5 times in a 10 sec time interval will trigger the frequency of occurrence threshold.","In one embodiment, a disturbance may be considered to adversely affect signal integrity in the communication systems 1655 when the duration threshold alone is exceeded.","In another embodiment, a disturbance may be considered as adversely affecting signal integrity in the communication systems 1655 when both the duration threshold and the frequency of occurrence threshold are exceeded.","The latter embodiment is thus more conservative than the former embodiment for classifying disturbances that adversely affect signal integrity in the communication system 1655.It will be appreciated that many other algorithms and associated parameters and thresholds can be utilized for step 1710 in accordance with example embodiments.","Referring back to method 1700, if at step 1710 the disturbance detected at step 1708 does not meet the condition for adversely affected communications (e.g., neither exceeds the duration threshold nor the frequency of occurrence threshold), the waveguide system 1602 may proceed to step 1702 and continue processing messages.","For instance, if the disturbance detected in step 1708 has a duration of 1 msec with a single occurrence in a 10 sec time period, then neither threshold will be exceeded.","Consequently, such a disturbance may be considered as having a nominal effect on signal integrity in the communication system 1655 and thus would not be flagged as a disturbance requiring mitigation.","Although not flagged, the occurrence of the disturbance, its time of occurrence, its frequency of occurrence, spectral data, and/or other useful information, may be reported to the network management system 1601 as telemetry data for monitoring purposes.","Referring back to step 1710, if on the other hand the disturbance satisfies the condition for adversely affected communications (e.g., exceeds either or both thresholds), the waveguide system 1602 can proceed to step 1712 and report the incident to the network management system 1601.The report can include raw sensing data collected by the sensors 1604, a description of the disturbance if known by the waveguide system 1602, a time of occurrence of the disturbance, a frequency of occurrence of the disturbance, a location associated with the disturbance, parameters readings such as bit error rate, packet loss rate, retransmission requests, jitter, latency and so on.","If the disturbance is based on a prediction by one or more sensors of the waveguide system 1602, the report can include a type of disturbance expected, and if predictable, an expected time occurrence of the disturbance, and an expected frequency of occurrence of the predicted disturbance when the prediction is based on historical sensing data collected by the sensors 1604 of the waveguide system 1602.At step 1714, the network management system 1601 can determine a mitigation, circumvention, or correction technique, which may include directing the waveguide system 1602 to reroute traffic to circumvent the disturbance if the location of the disturbance can be determined.","In one embodiment, the waveguide coupling device 1402 detecting the disturbance may direct a repeater such as the one shown in FIGS.","13-14 to connect the waveguide system 1602 from a primary power line affected by the disturbance to a secondary power line to enable the waveguide system 1602 to reroute traffic to a different transmission medium and avoid the disturbance.","In an embodiment where the waveguide system 1602 is configured as a repeater the waveguide system 1602 can itself perform the rerouting of traffic from the primary power line to the secondary power line.","It is further noted that for bidirectional communications (e.g., full or half-duplex communications), the repeater can be configured to reroute traffic from the secondary power line back to the primary power line for processing by the waveguide system 1602.In another embodiment, the waveguide system 1602 can redirect traffic by instructing a first repeater situated upstream of the disturbance and a second repeater situated downstream of the disturbance to redirect traffic from a primary power line temporarily to a secondary power line and back to the primary power line in a manner that avoids the disturbance.","It is further noted that for bidirectional communications (e.g., full or half-duplex communications), repeaters can be configured to reroute traffic from the secondary power line back to the primary power line.","To avoid interrupting existing communication sessions occurring on a secondary power line, the network management system 1601 may direct the waveguide system 1602 to instruct repeater(s) to utilize unused time slot(s) and/or frequency band(s) of the secondary power line for redirecting data and/or voice traffic away from the primary power line to circumvent the disturbance.","At step 1716, while traffic is being rerouted to avoid the disturbance, the network management system 1601 can notify equipment of the utility company 1652 and/or equipment of the communications service provider 1654, which in turn may notify personnel of the utility company 1656 and/or personnel of the communications service provider 1658 of the detected disturbance and its location if known.","Field personnel from either party can attend to resolving the disturbance at a determined location of the disturbance.","Once the disturbance is removed or otherwise mitigated by personnel of the utility company and/or personnel of the communications service provider, such personnel can notify their respective companies and/or the network management system 1601 utilizing field equipment (e.g., a laptop computer, smartphone, etc.)","communicatively coupled to network management system 1601, and/or equipment of the utility company and/or the communications service provider.","The notification can include a description of how the disturbance was mitigated and any changes to the power lines 1610 that may change a topology of the communication system 1655.Once the disturbance has been resolved (as determined in decision 1718), the network management system 1601 can direct the waveguide system 1602 at step 1720 to restore the previous routing configuration used by the waveguide system 1602 or route traffic according to a new routing configuration if the restoration strategy used to mitigate the disturbance resulted in a new network topology of the communication system 1655.In another embodiment, the waveguide system 1602 can be configured to monitor mitigation of the disturbance by transmitting test signals on the power line 1610 to determine when the disturbance has been removed.","Once the waveguide system 1602 detects an absence of the disturbance it can autonomously restore its routing configuration without assistance by the network management system 1601 if it determines the network topology of the communication system 1655 has not changed, or it can utilize a new routing configuration that adapts to a detected new network topology.","FIG.","17B illustrates a flow diagram of an example, non-limiting embodiment of a method 1750 for detecting and mitigating disturbances occurring in a communication network of the system of FIGS.","16A-16C.","In one embodiment, method 1750 can begin with step 1752 where a network management system 1601 receives from equipment of the utility company 1652 or equipment of the communications service provider 1654 maintenance information associated with a maintenance schedule.","The network management system 1601 can at step 1754 identify from the maintenance information, maintenance activities to be performed during the maintenance schedule.","From these activities, the network management system 1601 can detect a disturbance resulting from the maintenance (e.g., scheduled replacement of a power line 1610, scheduled replacement of a waveguide system 1602 on the power line 1610, scheduled reconfiguration of power lines 1610 in the power grid 1653, etc.).","In another embodiment, the network management system 1601 can receive at step 1755 telemetry information from one or more waveguide systems 1602.The telemetry information can include among other things an identity of each waveguide system 1602 submitting the telemetry information, measurements taken by sensors 1604 of each waveguide system 1602, information relating to predicted, estimated, or actual disturbances detected by the sensors 1604 of each waveguide system 1602, location information associated with each waveguide system 1602, an estimated location of a detected disturbance, an identification of the disturbance, and so on.","The network management system 1601 can determine from the telemetry information a type of disturbance that may be adverse to operations of the waveguide, transmission of the electromagnetic waves along the wire surface, or both.","The network management system 1601 can also use telemetry information from multiple waveguide systems 1602 to isolate and identify the disturbance.","Additionally, the network management system 1601 can request telemetry information from waveguide systems 1602 in a vicinity of an affected waveguide system 1602 to triangulate a location of the disturbance and/or validate an identification of the disturbance by receiving similar telemetry information from other waveguide systems 1602.In yet another embodiment, the network management system 1601 can receive at step 1756 an unscheduled activity report from maintenance field personnel.","Unscheduled maintenance may occur as result of field calls that are unplanned or as a result of unexpected field issues discovered during field calls or scheduled maintenance activities.","The activity report can identify changes to a topology configuration of the power grid 1653 resulting from field personnel addressing discovered issues in the communication system 1655 and/or power grid 1653, changes to one or more waveguide systems 1602 (such as replacement or repair thereof), mitigation of disturbances performed if any, and so on.","At step 1758, the network management system 1601 can determine from reports received according to steps 1752 through 1756 if a disturbance will occur based on a maintenance schedule, or if a disturbance has occurred or is predicted to occur based on telemetry data, or if a disturbance has occurred due to an unplanned maintenance identified in a field activity report.","From any of these reports, the network management system 1601 can determine whether a detected or predicted disturbance requires rerouting of traffic by the affected waveguide systems 1602 or other waveguide systems 1602 of the communication system 1655.When a disturbance is detected or predicted at step 1758, the network management system 1601 can proceed to step 1760 where it can direct one or more waveguide systems 1602 to reroute traffic to circumvent the disturbance.","When the disturbance is permanent due to a permanent topology change of the power grid 1653, the network management system 1601 can proceed to step 1770 and skip steps 1762, 1764, 1766, and 1772.At step 1770, the network management system 1601 can direct one or more waveguide systems 1602 to use a new routing configuration that adapts to the new topology.","However, when the disturbance has been detected from telemetry information supplied by one or more waveguide systems 1602, the network management system 1601 can notify maintenance personnel of the utility company 1656 or the communications service provider 1658 of a location of the disturbance, a type of disturbance if known, and related information that may be helpful to such personnel to mitigate the disturbance.","When a disturbance is expected due to maintenance activities, the network management system 1601 can direct one or more waveguide systems 1602 to reconfigure traffic routes at a given schedule (consistent with the maintenance schedule) to avoid disturbances caused by the maintenance activities during the maintenance schedule.","Returning back to step 1760 and upon its completion, the process can continue with step 1762.At step 1762, the network management system 1601 can monitor when the disturbance(s) have been mitigated by field personnel.","Mitigation of a disturbance can be detected at step 1762 by analyzing field reports submitted to the network management system 1601 by field personnel over a communications network (e.g., cellular communication system) utilizing field equipment (e.g., a laptop computer or handheld computer/device).","If field personnel have reported that a disturbance has been mitigated, the network management system 1601 can proceed to step 1764 to determine from the field report whether a topology change was required to mitigate the disturbance.","A topology change can include rerouting a power line 1610, reconfiguring a waveguide system 1602 to utilize a different power line 1610, otherwise utilizing an alternative link to bypass the disturbance and so on.","If a topology change has taken place, the network management system 1601 can direct at step 1770 one or more waveguide systems 1602 to use a new routing configuration that adapts to the new topology.","If, however, a topology change has not been reported by field personnel, the network management system 1601 can proceed to step 1766 where it can direct one or more waveguide systems 1602 to send test signals to test a routing configuration that had been used prior to the detected disturbance(s).","Test signals can be sent to affected waveguide systems 1602 in a vicinity of the disturbance.","The test signals can be used to determine if signal disturbances (e.g., electromagnetic wave reflections) are detected by any of the waveguide systems 1602.If the test signals confirm that a prior routing configuration is no longer subject to previously detected disturbance(s), then the network management system 1601 can at step 1772 direct the affected waveguide systems 1602 to restore a previous routing configuration.","If, however, test signals analyzed by one or more waveguide coupling device 1402 and reported to the network management system 1601 indicate that the disturbance(s) or new disturbance(s) are present, then the network management system 1601 will proceed to step 1768 and report this information to field personnel to further address field issues.","The network management system 1601 can in this situation continue to monitor mitigation of the disturbance(s) at step 1762.In the aforementioned embodiments, the waveguide systems 1602 can be configured to be self-adapting to changes in the power grid 1653 and/or to mitigation of disturbances.","That is, one or more affected waveguide systems 1602 can be configured to self-monitor mitigation of disturbances and reconfigure traffic routes without requiring instructions to be sent to them by the network management system 1601.In this embodiment, the one or more waveguide systems 1602 that are self-configurable can inform the network management system 1601 of its routing choices so that the network management system 1601 can maintain a macro-level view of the communication topology of the communication system 1655.While for purposes of simplicity of explanation, the respective processes are shown and described as a series of blocks in FIGS.","17A and 17B, respectively, it is to be understood and appreciated that the claimed subject matter is not limited by the order of the blocks, as some blocks may occur in different orders and/or concurrently with other blocks from what is depicted and described herein.","Moreover, not all illustrated blocks may be required to implement the methods described herein.","Turning now to FIG.","18, a block diagram illustrating an example, non-limiting embodiment of a cross-sectional view of transmission media 1800 in accordance with various aspects described herein is shown.","In one embodiment, transmission media 1800 can comprise a bundle of power lines sharing a common cable.","FIG.","18 depicts a first power line 1804, a second power line 1806, and a third power line 1808 sharing a common cable 1802 that may itself be either another power line or a support cable used to support the bundle.","Other configurations of more or fewer power lines can be used in accordance with the embodiments of the subject disclosure.","The power lines 1804, 1806 and 1808 and common cable 1802 can be coupled to multiple spacers such as the spacer 1900 depicted in FIG.","19.Each spacer 1900 can have clamps 1902 which can be used to support the power lines 1804, 1806 and 1808 and the common cable 1802.For power lines held by utility poles over long distances, the spacers 1900 can be separated longitudinally from each other such as to achieve a uniform spacing between the power lines 1804, 1806 and 1808 and the common cable 1802.The power lines 1804, 1806 and 1808 can be constructed with insulated or uninsulated conductors.","Similarly, the common cable 1802 can be an insulated or uninsulated conductor.","In various embodiments, the bundle of power lines 1804, 1806 and 1808 share the common cable 1802 in order to support multiple electromagnetic communication paths.","For example, the separation between the common cable 1802 and the first power line 1804 can form a first twin-lead cable, which can be used for propagating a first electromagnetic wave 1804′ that propagates longitudinally along the first power line 1804 and the common cable 1802 and at least a portion of the area in between (i.e., in a longitudinal direction that points in and/or out of the page).","Similarly, the separation between the common cable 1802 and the second power line 1806 can form a second twin-lead cable, which can be used for propagating a second electromagnetic wave 1806′ that propagates longitudinally along the second power line 1806 and the common cable 1802 and at least a portion of the area in between.","Lastly, the separation between the common cable 1802 and the third power line 1808 can form a third twin-lead cable, which can be used for propagating a third electromagnetic wave 1808′ that propagates longitudinally along the third power line 1806 and the common cable 1802 and at least a portion of the area in between.","Each twin-lead pair can serve as a transmission line for propagation of guided electromagnetic waves.","From the illustration of FIG.","18, a relationship exists between the number of cables and the number of twin-leads that can be used.","Particularly, N−1 twin-leads can be formed from a bundle of cables, where N is a sum of a total number of power lines and the common cable.","Based on FIG.","18, three twin-lead cables (four total cables−one) are possible.","Each twin-lead cable can have an impedance range (e.g., from 600 ohms to 75 ohms) that determines an operating frequency range of electromagnetic waves that can be guided by each twin-lead cable (e.g., 3 KHz to 300 GHz).","The embodiments of FIGS.","18-19 can also be combined with the embodiments described earlier for transporting electromagnetic waves on a single transmission medium.","For example, a waveguide system 1602 such as described earlier in FIG.","16A can be configured to exchange electromagnetic waves with other waveguide systems 1602 over the first power line 1804, while at the same time another system exchanges electromagnetic waves guided by the twin-lead comprising the first power line 1804 and the common cable 1802.Guided electromagnetic waves can also be transmitted individually on the second power line 1806, the third power line 1808 and the common cable 1802.Accordingly, the configuration of FIG.","18, can be used as seven communication pathways: A) three communication pathways via the three twin-lead cables, and B) four communication pathways via the four cables used for exchanging electromagnetic waves traveling on an outer surface of each cable.","Turning now to FIG.","20, a flow diagram of an example, non-limiting embodiment of a method 2000 that can be used for exchanging electromagnetic waves with transmission lines depicted in FIG.","18 in accordance with various aspects described herein is shown.","Method 2002 can begin with a plurality of launchers receiving a plurality of communication signals.","Each launcher can be configured to receive a select one of the communication signals.","Each communication signal can include data such as voice, streaming content or other forms of communication data generated by different sources.","At step 2004, the launchers can be configured to transmit a plurality of electromagnetic waves by way of the bundle of transmission media 1800 such as shown in FIG.","18.Each twin-lead of the bundle of transmission media 1800, for example, can be connected to a launcher (not shown) which can launch between the power line and the common cable forming an electromagnetic wave guided by the twin-lead, which can propagate longitudinally to a receiver (not shown) at a downstream location.","In one embodiment, the plurality of launchers can be integrated with the spacer 1900 of FIG.","19.Each launcher can have a coupler that, for example, makes contact with a corresponding power lines supported by clamp 1902 to excite an electromagnetic wave at a corresponding cable pairs of each twin lead, including the shared cable.","The launcher can be a radio frequency (RF) transmitter that includes RF circuits for modulating and transmitting RF signals.","Similarly, the receiver can be an RF receiver that includes RF circuits for receiving and demodulating RF signals.","At step 2006, downstream receivers, each coupled to a particular twin-lead of the bundle of transmission media 1800, can receive the electromagnetic wave and retrieve at step 2008 a corresponding communication signal.","For bi-directional communications, method 2000 can be adapted so that launchers and receivers are combined to form transceivers at each end such as the transmission devices 101 and 102 of FIG.","1 for transmitting guided waves 120 and 122, respectively.","As noted earlier, the individual cables of the bundled transmission media 1800 can also be used for exchanging electromagnetic waves on an outer surface of each cable.","Accordingly, method 2000 can be adapted to use waveguide systems to add more communication pathways if so desired.","It is further noted that a dipole antenna can be used as a launcher to excite and/or extract energy from each twin lead transmission line previously described by the illustration of FIG.","18.For example, the ends of the dipole antenna can be sized to fit between the conductors of the twin lead (orthogonal to them), can be positioned in a same plane as the spacer 1900 and oriented between the shared cable and corresponding power line in order to send and receive guided wave communication via the corresponding twin lead communication path.","In some embodiments, a dipole antenna can be placed where line 1804′ is shown in FIG.","18, and can be supplied signals at center feed points of the antenna.","In one embodiment, the spacer 1900 can be configured with a dipole antenna painted or otherwise integrated onto or molded inside a plastic material of the spacer 1900.The dimensions of the dipole antenna can dictate an operating frequency of signals supplied to the twin lead.","In one embodiment, the electronics of the launcher can be molded into the spacer 1900, and can be configured to draw power from any two conductors held by the spacer 1900.In another embodiment, a millimeter wave or terahertz communication device having a small antenna can be positioned at a center location of the spacer 1900 (e.g., diamond shaped null 1903).","The transmitter can be configured to transmit signals that support very high bandwidth communications between spacers 1900 using the open space between the wires supported by the spacers 1900.It will be appreciated that the foregoing embodiments can also be adapted without the use of a spacer 1900.For example, the embodiments of the subject disclosure can be applied to any two parallel suspended conductors as a twin lead transmission line, including those that hang at a top section of a utility pole (without a spacer 1900).","To accommodate variable spacing between conductors not supported by spacers 1900, an operating frequency of the electromagnetic waves supplied to the twin leads can be lowered to provide reliable communications.","In one embodiment, a (dipole) coupler antenna system a Yagi antenna, or other launcher can be attached to a cross arm at a top section of a utility pole to supply electromagnetic wave signals to pairs of power lines (not supported by spacers 1900) that are being used as a twin lead.","Other variants of the subject disclosure are contemplated.","While for purposes of simplicity of explanation, the respective processes are shown and described as a series of blocks in FIG.","20, it is to be understood and appreciated that the claimed subject matter is not limited by the order of the blocks, as some blocks may occur in different orders and/or concurrently with other blocks from what is depicted and described herein.","Moreover, not all illustrated blocks may be required to implement the methods described herein.","Referring now to FIG.","21, there is illustrated a block diagram of a computing environment in accordance with various aspects described herein.","In order to provide additional context for various embodiments of the embodiments described herein, FIG.","21 and the following discussion are intended to provide a brief, general description of a suitable computing environment 2100 in which the various embodiments of the subject disclosure can be implemented.","While the embodiments have been described above in the general context of computer-executable instructions that can run on one or more computers, those skilled in the art will recognize that the embodiments can be also implemented in combination with other program modules and/or as a combination of hardware and software.","Generally, program modules comprise routines, programs, components, data structures, etc., that perform particular tasks or implement particular abstract data types.","Moreover, those skilled in the art will appreciate that the inventive methods can be practiced with other computer system configurations, comprising single-processor or multiprocessor computer systems, minicomputers, mainframe computers, as well as personal computers, hand-held computing devices, microprocessor-based or programmable consumer electronics, and the like, each of which can be operatively coupled to one or more associated devices.","As used herein, a processing circuit includes processor as well as other application specific circuits such as an application specific integrated circuit, digital logic circuit, state machine, programmable gate array or other circuit that processes input signals or data and that produces output signals or data in response thereto.","It should be noted that while any functions and features described herein in association with the operation of a processor could likewise be performed by a processing circuit.","The terms “first,” “second,” “third,” and so forth, as used in the claims, unless otherwise clear by context, is for clarity only and doesn't otherwise indicate or imply any order in time.","For instance, “a first determination,” “a second determination,” and “a third determination,” does not indicate or imply that the first determination is to be made before the second determination, or vice versa, etc.","The illustrated embodiments of the embodiments herein can be also practiced in distributed computing environments where certain tasks are performed by remote processing devices that are linked through a communications network.","In a distributed computing environment, program modules can be located in both local and remote memory storage devices.","Computing devices typically comprise a variety of media, which can comprise computer-readable storage media and/or communications media, which two terms are used herein differently from one another as follows.","Computer-readable storage media can be any available storage media that can be accessed by the computer and comprises both volatile and nonvolatile media, removable and non-removable media.","By way of example, and not limitation, computer-readable storage media can be implemented in connection with any method or technology for storage of information such as computer-readable instructions, program modules, structured data or unstructured data.","Computer-readable storage media can comprise, but are not limited to, random access memory (RAM), read only memory (ROM), electrically erasable programmable read only memory (EEPROM), flash memory or other memory technology, compact disk read only memory (CD-ROM), digital versatile disk (DVD) or other optical disk storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices or other tangible and/or non-transitory media which can be used to store desired information.","In this regard, the terms “tangible” or “non-transitory” herein as applied to storage, memory or computer-readable media, are to be understood to exclude only propagating transitory signals per se as modifiers and do not relinquish rights to all standard storage, memory or computer-readable media that are not only propagating transitory signals per se.","Computer-readable storage media can be accessed by one or more local or remote computing devices, e.g., via access requests, queries or other data retrieval protocols, for a variety of operations with respect to the information stored by the medium.","Communications media typically embody computer-readable instructions, data structures, program modules or other structured or unstructured data in a data signal such as a modulated data signal, e.g., a carrier wave or other transport mechanism, and comprises any information delivery or transport media.","The term “modulated data signal” or signals refers to a signal that has one or more of its characteristics set or changed in such a manner as to encode information in one or more signals.","By way of example, and not limitation, communication media comprise wired media, such as a wired network or direct-wired connection, and wireless media such as acoustic, RF, infrared and other wireless media.","With reference again to FIG.","21, the example environment 2100 for transmitting and receiving signals via or forming at least part of a base station (e.g., base station devices 1504, macrocell site 1502, or base stations 1614) or central office (e.g., central office 1501 or 1611).","At least a portion of the example environment 2100 can also be used for transmission devices 101 or 102.The example environment can comprise a computer 2102, the computer 2102 comprising a processing unit 2104, a system memory 2106 and a system bus 2108.The system bus 2108 couples system components including, but not limited to, the system memory 2106 to the processing unit 2104.The processing unit 2104 can be any of various commercially available processors.","Dual microprocessors and other multiprocessor architectures can also be employed as the processing unit 2104.The system bus 2108 can be any of several types of bus structure that can further interconnect to a memory bus (with or without a memory controller), a peripheral bus, and a local bus using any of a variety of commercially available bus architectures.","The system memory 2106 comprises ROM 2110 and RAM 2112.A basic input/output system (BIOS) can be stored in a non-volatile memory such as ROM, erasable programmable read only memory (EPROM), EEPROM, which BIOS contains the basic routines that help to transfer information between elements within the computer 2102, such as during startup.","The RAM 2112 can also comprise a high-speed RAM such as static RAM for caching data.","The computer 2102 further comprises an internal hard disk drive (HDD) 2114 (e.g., EIDE, SATA), which internal hard disk drive 2114 can also be configured for external use in a suitable chassis (not shown), a magnetic floppy disk drive (FDD) 2116, (e.g., to read from or write to a removable diskette 2118) and an optical disk drive 2120, (e.g., reading a CD-ROM disk 2122 or, to read from or write to other high capacity optical media such as the DVD).","The hard disk drive 2114, magnetic disk drive 2116 and optical disk drive 2120 can be connected to the system bus 2108 by a hard disk drive interface 2124, a magnetic disk drive interface 2126 and an optical drive interface 2128, respectively.","The interface 2124 for external drive implementations comprises at least one or both of Universal Serial Bus (USB) and Institute of Electrical and Electronics Engineers (IEEE) 1394 interface technologies.","Other external drive connection technologies are within contemplation of the embodiments described herein.","The drives and their associated computer-readable storage media provide nonvolatile storage of data, data structures, computer-executable instructions, and so forth.","For the computer 2102, the drives and storage media accommodate the storage of any data in a suitable digital format.","Although the description of computer-readable storage media above refers to a hard disk drive (HDD), a removable magnetic diskette, and a removable optical media such as a CD or DVD, it should be appreciated by those skilled in the art that other types of storage media which are readable by a computer, such as zip drives, magnetic cassettes, flash memory cards, cartridges, and the like, can also be used in the example operating environment, and further, that any such storage media can contain computer-executable instructions for performing the methods described herein.","A number of program modules can be stored in the drives and RAM 2112, comprising an operating system 2130, one or more application programs 2132, other program modules 2134 and program data 2136.All or portions of the operating system, applications, modules, and/or data can also be cached in the RAM 2112.The systems and methods described herein can be implemented utilizing various commercially available operating systems or combinations of operating systems.","Examples of application programs 2132 that can be implemented and otherwise executed by processing unit 2104 include the diversity selection determining performed by transmission device 101 or 102.A user can enter commands and information into the computer 2102 through one or more wired/wireless input devices, e.g., a keyboard 2138 and a pointing device, such as a mouse 2140.Other input devices (not shown) can comprise a microphone, an infrared (IR) remote control, a joystick, a game pad, a stylus pen, touch screen or the like.","These and other input devices are often connected to the processing unit 2104 through an input device interface 2142 that can be coupled to the system bus 2108, but can be connected by other interfaces, such as a parallel port, an IEEE 1394 serial port, a game port, a universal serial bus (USB) port, an IR interface, etc.","A monitor 2144 or other type of display device can be also connected to the system bus 2108 via an interface, such as a video adapter 2146.It will also be appreciated that in alternative embodiments, a monitor 2144 can also be any display device (e.g., another computer having a display, a smart phone, a tablet computer, etc.)","for receiving display information associated with computer 2102 via any communication means, including via the Internet and cloud-based networks.","In addition to the monitor 2144, a computer typically comprises other peripheral output devices (not shown), such as speakers, printers, etc.","The computer 2102 can operate in a networked environment using logical connections via wired and/or wireless communications to one or more remote computers, such as a remote computer(s) 2148.The remote computer(s) 2148 can be a workstation, a server computer, a router, a personal computer, portable computer, microprocessor-based entertainment appliance, a peer device or other common network node, and typically comprises many or all of the elements described relative to the computer 2102, although, for purposes of brevity, only a memory/storage device 2150 is illustrated.","The logical connections depicted comprise wired/wireless connectivity to a local area network (LAN) 2152 and/or larger networks, e.g., a wide area network (WAN) 2154.Such LAN and WAN networking environments are commonplace in offices and companies, and facilitate enterprise-wide computer networks, such as intranets, all of which can connect to a global communications network, e.g., the Internet.","When used in a LAN networking environment, the computer 2102 can be connected to the local network 2152 through a wired and/or wireless communication network interface or adapter 2156.The adapter 2156 can facilitate wired or wireless communication to the LAN 2152, which can also comprise a wireless AP disposed thereon for communicating with the wireless adapter 2156.When used in a WAN networking environment, the computer 2102 can comprise a modem 2158 or can be connected to a communications server on the WAN 2154 or has other means for establishing communications over the WAN 2154, such as by way of the Internet.","The modem 2158, which can be internal or external and a wired or wireless device, can be connected to the system bus 2108 via the input device interface 2142.In a networked environment, program modules depicted relative to the computer 2102 or portions thereof, can be stored in the remote memory/storage device 2150.It will be appreciated that the network connections shown are example and other means of establishing a communications link between the computers can be used.","The computer 2102 can be operable to communicate with any wireless devices or entities operatively disposed in wireless communication, e.g., a printer, scanner, desktop and/or portable computer, portable data assistant, communications satellite, any piece of equipment or location associated with a wirelessly detectable tag (e.g., a kiosk, news stand, restroom), and telephone.","This can comprise Wireless Fidelity (Wi-Fi) and BLUETOOTH® wireless technologies.","Thus, the communication can be a predefined structure as with a conventional network or simply an ad hoc communication between at least two devices.","Wi-Fi can allow connection to the Internet from a couch at home, a bed in a hotel room or a conference room at work, without wires.","Wi-Fi is a wireless technology similar to that used in a cell phone that enables such devices, e.g., computers, to send and receive data indoors and out; anywhere within the range of a base station.","Wi-Fi networks use radio technologies called IEEE 802.11 (a, b, g, n, ac, ag etc.)","to provide secure, reliable, fast wireless connectivity.","A Wi-Fi network can be used to connect computers to each other, to the Internet, and to wired networks (which can use IEEE 802.3 or Ethernet).","Wi-Fi networks operate in the unlicensed 2.4 and 5 GHz radio bands for example or with products that contain both bands (dual band), so the networks can provide real-world performance similar to the basic 10BaseT wired Ethernet networks used in many offices.","FIG.","22 presents an example embodiment 2200 of a mobile network platform 2210 that can implement and exploit one or more aspects of the disclosed subject matter described herein.","In one or more embodiments, the mobile network platform 2210 can generate and receive signals transmitted and received by base stations (e.g., base station devices 1504, macrocell site 1502, or base stations 1614), central office (e.g., central office 1501 or 1611), or transmission device 101 or 102 associated with the disclosed subject matter.","Generally, wireless network platform 2210 can comprise components, e.g., nodes, gateways, interfaces, servers, or disparate platforms, that facilitate both packet-switched (PS) (e.g., internet protocol (IP), frame relay, asynchronous transfer mode (ATM)) and circuit-switched (CS) traffic (e.g., voice and data), as well as control generation for networked wireless telecommunication.","As a non-limiting example, wireless network platform 2210 can be included in telecommunications carrier networks, and can be considered carrier-side components as discussed elsewhere herein.","Mobile network platform 2210 comprises CS gateway node(s) 2222 which can interface CS traffic received from legacy networks like telephony network(s) 2240 (e.g., public switched telephone network (PSTN), or public land mobile network (PLMN)) or a signaling system #7 (SS7) network 2270.Circuit switched gateway node(s) 2222 can authorize and authenticate traffic (e.g., voice) arising from such networks.","Additionally, CS gateway node(s) 2222 can access mobility, or roaming, data generated through SS7 network 2270; for instance, mobility data stored in a visited location register (VLR), which can reside in memory 2230.Moreover, CS gateway node(s) 2222 interfaces CS-based traffic and signaling and PS gateway node(s) 2218.As an example, in a 3GPP UMTS network, CS gateway node(s) 2222 can be realized at least in part in gateway GPRS support node(s) (GGSN).","It should be appreciated that functionality and specific operation of CS gateway node(s) 2222, PS gateway node(s) 2218, and serving node(s) 2216, is provided and dictated by radio technology(ies) utilized by mobile network platform 2210 for telecommunication.","In addition to receiving and processing CS-switched traffic and signaling, PS gateway node(s) 2218 can authorize and authenticate PS-based data sessions with served mobile devices.","Data sessions can comprise traffic, or content(s), exchanged with networks external to the wireless network platform 2210, like wide area network(s) (WANs) 2250, enterprise network(s) 2270, and service network(s) 2280, which can be embodied in local area network(s) (LANs), can also be interfaced with mobile network platform 2210 through PS gateway node(s) 2218.It is to be noted that WANs 2250 and enterprise network(s) 2260 can embody, at least in part, a service network(s) like IP multimedia subsystem (IMS).","Based on radio technology layer(s) available in technology resource(s) 2217, packet-switched gateway node(s) 2218 can generate packet data protocol contexts when a data session is established; other data structures that facilitate routing of packetized data also can be generated.","To that end, in an aspect, PS gateway node(s) 2218 can comprise a tunnel interface (e.g., tunnel termination gateway (TTG) in 3GPP UMTS network(s) (not shown)) which can facilitate packetized communication with disparate wireless network(s), such as Wi-Fi networks.","In embodiment 2200, wireless network platform 2210 also comprises serving node(s) 2216 that, based upon available radio technology layer(s) within technology resource(s) 2217, convey the various packetized flows of data streams received through PS gateway node(s) 2218.It is to be noted that for technology resource(s) 2217 that rely primarily on CS communication, server node(s) can deliver traffic without reliance on PS gateway node(s) 2218; for example, server node(s) can embody at least in part a mobile switching center.","As an example, in a 3GPP UMTS network, serving node(s) 2216 can be embodied in serving GPRS support node(s) (SGSN).","For radio technologies that exploit packetized communication, server(s) 2214 in wireless network platform 2210 can execute numerous applications that can generate multiple disparate packetized data streams or flows, and manage (e.g., schedule, queue, format .",".",". )","such flows.","Such application(s) can comprise add-on features to standard services (for example, provisioning, billing, customer support .",".",". )","provided by wireless network platform 2210.Data streams (e.g., content(s) that are part of a voice call or data session) can be conveyed to PS gateway node(s) 2218 for authorization/authentication and initiation of a data session, and to serving node(s) 2216 for communication thereafter.","In addition to application server, server(s) 2214 can comprise utility server(s), a utility server can comprise a provisioning server, an operations and maintenance server, a security server that can implement at least in part a certificate authority and firewalls as well as other security mechanisms, and the like.","In an aspect, security server(s) secure communication served through wireless network platform 2210 to ensure network's operation and data integrity in addition to authorization and authentication procedures that CS gateway node(s) 2222 and PS gateway node(s) 2218 can enact.","Moreover, provisioning server(s) can provision services from external network(s) like networks operated by a disparate service provider; for instance, WAN 2250 or Global Positioning System (GPS) network(s) (not shown).","Provisioning server(s) can also provision coverage through networks associated to wireless network platform 2210 (e.g., deployed and operated by the same service provider), such as the distributed antennas networks shown in FIG.","1(s) that enhance wireless service coverage by providing more network coverage.","Repeater devices such as those shown in FIGS.","7, 8, and 9 also improve network coverage in order to enhance subscriber service experience by way of UE 2275.It is to be noted that server(s) 2214 can comprise one or more processors configured to confer at least in part the functionality of macro network platform 2210.To that end, the one or more processor can execute code instructions stored in memory 2230, for example.","It is should be appreciated that server(s) 2214 can comprise a content manager 2215, which operates in substantially the same manner as described hereinbefore.","In example embodiment 2200, memory 2230 can store information related to operation of wireless network platform 2210.Other operational information can comprise provisioning information of mobile devices served through wireless platform network 2210, subscriber databases; application intelligence, pricing schemes, e.g., promotional rates, flat-rate programs, couponing campaigns; technical specification(s) consistent with telecommunication protocols for operation of disparate radio, or wireless, technology layers; and so forth.","Memory 2230 can also store information from at least one of telephony network(s) 2240, WAN 2250, enterprise network(s) 2270, or SS7 network 2260.In an aspect, memory 2230 can be, for example, accessed as part of a data store component or as a remotely connected memory store.","In order to provide a context for the various aspects of the disclosed subject matter, FIG.","22, and the following discussion, are intended to provide a brief, general description of a suitable environment in which the various aspects of the disclosed subject matter can be implemented.","While the subject matter has been described above in the general context of computer-executable instructions of a computer program that runs on a computer and/or computers, those skilled in the art will recognize that the disclosed subject matter also can be implemented in combination with other program modules.","Generally, program modules comprise routines, programs, components, data structures, etc.","that perform particular tasks and/or implement particular abstract data types.","FIG.","23 depicts an illustrative embodiment of a communication device 2300.The communication device 2300 can serve as an illustrative embodiment of devices such as mobile devices and in-building devices referred to by the subject disclosure (e.g., in FIGS.","15, 16A-16C).","The communication device 2300 can comprise a wireline and/or wireless transceiver 2302 (herein transceiver 2302), a user interface (UI) 2304, a power supply 2314, a location receiver 2316, a motion sensor 2318, an orientation sensor 2320, and a controller 2306 for managing operations thereof.","The transceiver 2302 can support short-range or long-range wireless access technologies such as Bluetooth®, ZigBee®, WiFi, DECT, or cellular communication technologies, just to mention a few (Bluetooth® and ZigBee® are trademarks registered by the Bluetooth® Special Interest Group and the ZigBee® Alliance, respectively).","Cellular technologies can include, for example, CDMA-1×, UMTS/HSDPA, GSM/GPRS, TDMA/EDGE, EV/DO, WiMAX, SDR, LTE, as well as other next generation wireless communication technologies as they arise.","The transceiver 2302 can also be adapted to support circuit-switched wireline access technologies (such as PSTN), packet-switched wireline access technologies (such as TCP/IP, VoIP, etc.","), and combinations thereof.","The UI 2304 can include a depressible or touch-sensitive keypad 2308 with a navigation mechanism such as a roller ball, a joystick, a mouse, or a navigation disk for manipulating operations of the communication device 2300.The keypad 2308 can be an integral part of a housing assembly of the communication device 2300 or an independent device operably coupled thereto by a tethered wireline interface (such as a USB cable) or a wireless interface supporting for example Bluetooth®.","The keypad 2308 can represent a numeric keypad commonly used by phones, and/or a QWERTY keypad with alphanumeric keys.","The UI 2304 can further include a display 2310 such as monochrome or color LCD (Liquid Crystal Display), OLED (Organic Light Emitting Diode) or other suitable display technology for conveying images to an end user of the communication device 2300.In an embodiment where the display 2310 is touch-sensitive, a portion or all of the keypad 2308 can be presented by way of the display 2310 with navigation features.","The display 2310 can use touch screen technology to also serve as a user interface for detecting user input.","As a touch screen display, the communication device 2300 can be adapted to present a user interface having graphical user interface (GUI) elements that can be selected by a user with a touch of a finger.","The touch screen display 2310 can be equipped with capacitive, resistive or other forms of sensing technology to detect how much surface area of a user's finger has been placed on a portion of the touch screen display.","This sensing information can be used to control the manipulation of the GUI elements or other functions of the user interface.","The display 2310 can be an integral part of the housing assembly of the communication device 2300 or an independent device communicatively coupled thereto by a tethered wireline interface (such as a cable) or a wireless interface.","The UI 2304 can also include an audio system 2312 that utilizes audio technology for conveying low volume audio (such as audio heard in proximity of a human ear) and high volume audio (such as speakerphone for hands free operation).","The audio system 2312 can further include a microphone for receiving audible signals of an end user.","The audio system 2312 can also be used for voice recognition applications.","The UI 2304 can further include an image sensor 2313 such as a charged coupled device (CCD) camera for capturing still or moving images.","The power supply 2314 can utilize common power management technologies such as replaceable and rechargeable batteries, supply regulation technologies, and/or charging system technologies for supplying energy to the components of the communication device 2300 to facilitate long-range or short-range portable communications.","Alternatively, or in combination, the charging system can utilize external power sources such as DC power supplied over a physical interface such as a USB port or other suitable tethering technologies.","The location receiver 2316 can utilize location technology such as a global positioning system (GPS) receiver capable of assisted GPS for identifying a location of the communication device 2300 based on signals generated by a constellation of GPS satellites, which can be used for facilitating location services such as navigation.","The motion sensor 2318 can utilize motion sensing technology such as an accelerometer, a gyroscope, or other suitable motion sensing technology to detect motion of the communication device 2300 in three-dimensional space.","The orientation sensor 2320 can utilize orientation sensing technology such as a magnetometer to detect the orientation of the communication device 2300 (north, south, west, and east, as well as combined orientations in degrees, minutes, or other suitable orientation metrics).","The communication device 2300 can use the transceiver 2302 to also determine a proximity to a cellular, WiFi, Bluetooth®, or other wireless access points by sensing techniques such as utilizing a received signal strength indicator (RSSI) and/or signal time of arrival (TOA) or time of flight (TOF) measurements.","The controller 2306 can utilize computing technologies such as a microprocessor, a digital signal processor (DSP), programmable gate arrays, application specific integrated circuits, and/or a video processor with associated storage memory such as Flash, ROM, RAM, SRAM, DRAM or other storage technologies for executing computer instructions, controlling, and processing data supplied by the aforementioned components of the communication device 2300.Other components not shown in FIG.","23 can be used in one or more embodiments of the subject disclosure.","For instance, the communication device 2300 can include a slot for adding or removing an identity module such as a Subscriber Identity Module (SIM) card or Universal Integrated Circuit Card (UICC).","SIM or UICC cards can be used for identifying subscriber services, executing programs, storing subscriber data, and so on.","In the subject specification, terms such as “store,” “storage,” “data store,” data storage,” “database,” and substantially any other information storage component relevant to operation and functionality of a component, refer to “memory components,” or entities embodied in a “memory” or components comprising the memory.","It will be appreciated that the memory components described herein can be either volatile memory or nonvolatile memory, or can comprise both volatile and nonvolatile memory, by way of illustration, and not limitation, volatile memory, non-volatile memory, disk storage, and memory storage.","Further, nonvolatile memory can be included in read only memory (ROM), programmable ROM (PROM), electrically programmable ROM (EPROM), electrically erasable ROM (EEPROM), or flash memory.","Volatile memory can comprise random access memory (RAM), which acts as external cache memory.","By way of illustration and not limitation, RAM is available in many forms such as synchronous RAM (SRAM), dynamic RAM (DRAM), synchronous DRAM (SDRAM), double data rate SDRAM (DDR SDRAM), enhanced SDRAM (ESDRAM), Synchlink DRAM (SLDRAM), and direct Rambus RAM (DRRAM).","Additionally, the disclosed memory components of systems or methods herein are intended to comprise, without being limited to comprising, these and any other suitable types of memory.","Moreover, it will be noted that the disclosed subject matter can be practiced with other computer system configurations, comprising single-processor or multiprocessor computer systems, mini-computing devices, mainframe computers, as well as personal computers, hand-held computing devices (e.g., PDA, phone, smartphone, watch, tablet computers, netbook computers, etc.","), microprocessor-based or programmable consumer or industrial electronics, and the like.","The illustrated aspects can also be practiced in distributed computing environments where tasks are performed by remote processing devices that are linked through a communications network; however, some if not all aspects of the subject disclosure can be practiced on stand-alone computers.","In a distributed computing environment, program modules can be located in both local and remote memory storage devices.","Some of the embodiments described herein can also employ artificial intelligence (AI) to facilitate automating one or more features described herein.","For example, artificial intelligence can be used in optional training controller 230 evaluate and select candidate frequencies, modulation schemes, MIMO modes, and/or guided wave modes in order to maximize transfer efficiency.","The embodiments (e.g., in connection with automatically identifying acquired cell sites that provide a maximum value/benefit after addition to an existing communication network) can employ various AI-based schemes for carrying out various embodiments thereof.","Moreover, the classifier can be employed to determine a ranking or priority of the each cell site of the acquired network.","A classifier is a function that maps an input attribute vector, x=(x1, x2, x3, x4, .",".",".",", xn), to a confidence that the input belongs to a class, that is, f(x)=confidence (class).","Such classification can employ a probabilistic and/or statistical-based analysis (e.g., factoring into the analysis utilities and costs) to prognose or infer an action that a user desires to be automatically performed.","A support vector machine (SVM) is an example of a classifier that can be employed.","The SVM operates by finding a hypersurface in the space of possible inputs, which the hypersurface attempts to split the triggering criteria from the non-triggering events.","Intuitively, this makes the classification correct for testing data that is near, but not identical to training data.","Other directed and undirected model classification approaches comprise, e.g., naïve Bayes, Bayesian networks, decision trees, neural networks, fuzzy logic models, and probabilistic classification models providing different patterns of independence can be employed.","Classification as used herein also is inclusive of statistical regression that is utilized to develop models of priority.","As will be readily appreciated, one or more of the embodiments can employ classifiers that are explicitly trained (e.g., via a generic training data) as well as implicitly trained (e.g., via observing UE behavior, operator preferences, historical information, receiving extrinsic information).","For example, SVMs can be configured via a learning or training phase within a classifier constructor and feature selection module.","Thus, the classifier(s) can be used to automatically learn and perform a number of functions, including but not limited to determining according to a predetermined criteria which of the acquired cell sites will benefit a maximum number of subscribers and/or which of the acquired cell sites will add minimum value to the existing communication network coverage, etc.","As used in some contexts in this application, in some embodiments, the terms “component,” “system” and the like are intended to refer to, or comprise, a computer-related entity or an entity related to an operational apparatus with one or more specific functionalities, wherein the entity can be either hardware, a combination of hardware and software, software, or software in execution.","As an example, a component may be, but is not limited to being, a process running on a processor, a processor, an object, an executable, a thread of execution, computer-executable instructions, a program, and/or a computer.","By way of illustration and not limitation, both an application running on a server and the server can be a component.","One or more components may reside within a process and/or thread of execution and a component may be localized on one computer and/or distributed between two or more computers.","In addition, these components can execute from various computer readable media having various data structures stored thereon.","The components may communicate via local and/or remote processes such as in accordance with a signal having one or more data packets (e.g., data from one component interacting with another component in a local system, distributed system, and/or across a network such as the Internet with other systems via the signal).","As another example, a component can be an apparatus with specific functionality provided by mechanical parts operated by electric or electronic circuitry, which is operated by a software or firmware application executed by a processor, wherein the processor can be internal or external to the apparatus and executes at least a part of the software or firmware application.","As yet another example, a component can be an apparatus that provides specific functionality through electronic components without mechanical parts, the electronic components can comprise a processor therein to execute software or firmware that confers at least in part the functionality of the electronic components.","While various components have been illustrated as separate components, it will be appreciated that multiple components can be implemented as a single component, or a single component can be implemented as multiple components, without departing from example embodiments.","Further, the various embodiments can be implemented as a method, apparatus or article of manufacture using standard programming and/or engineering techniques to produce software, firmware, hardware or any combination thereof to control a computer to implement the disclosed subject matter.","The term “article of manufacture” as used herein is intended to encompass a computer program accessible from any computer-readable device or computer-readable storage/communications media.","For example, computer readable storage media can include, but are not limited to, magnetic storage devices (e.g., hard disk, floppy disk, magnetic strips), optical disks (e.g., compact disk (CD), digital versatile disk (DVD)), smart cards, and flash memory devices (e.g., card, stick, key drive).","Of course, those skilled in the art will recognize many modifications can be made to this configuration without departing from the scope or spirit of the various embodiments.","In addition, the words “example” and “exemplary” are used herein to mean serving as an instance or illustration.","Any embodiment or design described herein as “example” or “exemplary” is not necessarily to be construed as preferred or advantageous over other embodiments or designs.","Rather, use of the word example or exemplary is intended to present concepts in a concrete fashion.","As used in this application, the term “or” is intended to mean an inclusive “or” rather than an exclusive “or”.","That is, unless specified otherwise or clear from context, “X employs A or B” is intended to mean any of the natural inclusive permutations.","That is, if X employs A; X employs B; or X employs both A and B, then “X employs A or B” is satisfied under any of the foregoing instances.","In addition, the articles “a” and “an” as used in this application and the appended claims should generally be construed to mean “one or more” unless specified otherwise or clear from context to be directed to a singular form.","Moreover, terms such as “user equipment,” “mobile station,” “mobile,” subscriber station,” “access terminal,” “terminal,” “handset,” “mobile device” (and/or terms representing similar terminology) can refer to a wireless device utilized by a subscriber or user of a wireless communication service to receive or convey data, control, voice, video, sound, gaming or substantially any data-stream or signaling-stream.","The foregoing terms are utilized interchangeably herein and with reference to the related drawings.","Furthermore, the terms “user,” “subscriber,” “customer,” “consumer” and the like are employed interchangeably throughout, unless context warrants particular distinctions among the terms.","It should be appreciated that such terms can refer to human entities or automated components supported through artificial intelligence (e.g., a capacity to make inference based, at least, on complex mathematical formalisms), which can provide simulated vision, sound recognition and so forth.","As employed herein, the term “processor” can refer to substantially any computing processing unit or device comprising, but not limited to comprising, single-core processors; single-processors with software multithread execution capability; multi-core processors; multi-core processors with software multithread execution capability; multi-core processors with hardware multithread technology; parallel platforms; and parallel platforms with distributed shared memory.","Additionally, a processor can refer to an integrated circuit, an application specific integrated circuit (ASIC), a digital signal processor (DSP), a field programmable gate array (FPGA), a programmable logic controller (PLC), a complex programmable logic device (CPLD), a discrete gate or transistor logic, discrete hardware components or any combination thereof designed to perform the functions described herein.","Processors can exploit nano-scale architectures such as, but not limited to, molecular and quantum-dot based transistors, switches and gates, in order to optimize space usage or enhance performance of user equipment.","A processor can also be implemented as a combination of computing processing units.","As used herein, terms such as “data storage,” data storage,” “database,” and substantially any other information storage component relevant to operation and functionality of a component, refer to “memory components,” or entities embodied in a “memory” or components comprising the memory.","It will be appreciated that the memory components or computer-readable storage media, described herein can be either volatile memory or nonvolatile memory or can include both volatile and nonvolatile memory.","What has been described above includes mere examples of various embodiments.","It is, of course, not possible to describe every conceivable combination of components or methodologies for purposes of describing these examples, but one of ordinary skill in the art can recognize that many further combinations and permutations of the present embodiments are possible.","Accordingly, the embodiments disclosed and/or claimed herein are intended to embrace all such alterations, modifications and variations that fall within the spirit and scope of the appended claims.","Furthermore, to the extent that the term “includes” is used in either the detailed description or the claims, such term is intended to be inclusive in a manner similar to the term “comprising” as “comprising” is interpreted when employed as a transitional word in a claim.","In addition, a flow diagram may include a “start” and/or “continue” indication.","The “start” and “continue” indications reflect that the steps presented can optionally be incorporated in or otherwise used in conjunction with other routines.","In this context, “start” indicates the beginning of the first step presented and may be preceded by other activities not specifically shown.","Further, the “continue” indication reflects that the steps presented may be performed multiple times and/or may be succeeded by other activities not specifically shown.","Further, while a flow diagram indicates a particular ordering of steps, other orderings are likewise possible provided that the principles of causality are maintained.","As may also be used herein, the term(s) “operably coupled to”, “coupled to”, and/or “coupling” includes direct coupling between items and/or indirect coupling between items via one or more intervening items.","Such items and intervening items include, but are not limited to, junctions, communication paths, components, circuit elements, circuits, functional blocks, and/or devices.","As an example of indirect coupling, a signal conveyed from a first item to a second item may be modified by one or more intervening items by modifying the form, nature or format of information in a signal, while one or more elements of the information in the signal are nevertheless conveyed in a manner than can be recognized by the second item.","In a further example of indirect coupling, an action in a first item can cause a reaction on the second item, as a result of actions and/or reactions in one or more intervening items.","Although specific embodiments have been illustrated and described herein, it should be appreciated that any arrangement which achieves the same or similar purpose may be substituted for the embodiments described or shown by the subject disclosure.","The subject disclosure is intended to cover any and all adaptations or variations of various embodiments.","Combinations of the above embodiments, and other embodiments not specifically described herein, can be used in the subject disclosure.","For instance, one or more features from one or more embodiments can be combined with one or more features of one or more other embodiments.","In one or more embodiments, features that are positively recited can also be negatively recited and excluded from the embodiment with or without replacement by another structural and/or functional feature.","The steps or functions described with respect to the embodiments of the subject disclosure can be performed in any order.","The steps or functions described with respect to the embodiments of the subject disclosure can be performed alone or in combination with other steps or functions of the subject disclosure, as well as from other embodiments or from other steps that have not been described in the subject disclosure.","Further, more than or less than all of the features described with respect to an embodiment can also be utilized."]],"string":"[\n [\n \"METHOD AND APPARATUS FOR EXCHANGING COMMUNICATION SIGNALS\",\n \"Aspects of the subject disclosure may include, for example, receiving, by each of a plurality of receivers, one of a plurality of electromagnetic waves, each electromagnetic wave of the plurality of electromagnetic waves guided by a different one of a plurality of twin-lead transmission lines, each twin-lead transmission line sharing a wire, and each electromagnetic wave of the plurality of electromagnetic waves including a different one of a plurality of communication signals, and obtaining, by each of the plurality of receivers, one of the plurality of communication signals.\",\n \"Other embodiments are disclosed.\"\n ],\n [\n \"1.A device, comprising: an antenna that facilitates receiving an electromagnetic wave of a plurality of electromagnetic waves, wherein each electromagnetic wave of the plurality of electromagnetic waves is guided by a different one of a plurality of twin-lead transmission lines, wherein the plurality of electromagnetic waves propagate along the plurality of twin-lead transmission lines without requiring an electrical return path, and wherein each electromagnetic wave of the plurality of electromagnetic waves conveys a different one of a plurality of communication signals; and a receiver that facilitates obtaining, from the electromagnetic wave that is received by the antenna, the different one of the plurality of communication signals.\",\n \"2.The device of claim 1, wherein the antenna extracts energy from a twin-lead transmission line of the plurality of twin-lead transmission lines.\",\n \"3.The device of claim 1, wherein the antenna comprises a dipole antenna having elements disposed between conductors of each of the plurality of twin-lead transmission lines.\",\n \"4.The device of claim 1, wherein the antenna comprises a dipole antenna, and wherein an operating frequency of the different one of the communication signals is associated with dimensions of the dipole antenna.\",\n \"5.The device of claim 1, wherein the plurality of electromagnetic waves operates in a non-optical frequency range.\",\n \"6.The device of claim 1, wherein the plurality of twin-lead transmission lines comprise insulated conductors.\",\n \"7.The device of claim 1, wherein the plurality of twin-lead transmission lines comprise uninsulated conductors.\",\n \"8.The device of claim 1, wherein the plurality of twin-lead transmission lines comprise a plurality of twisted pairs of insulated conductors.\",\n \"9.The device of claim 8, wherein each respective twin-lead transmission line of the plurality of twin-lead transmission lines corresponds to a respective twisted pair of insulated conductors of the plurality of twisted pairs of insulated conductors.\",\n \"10.The device of claim 1, wherein the antenna is positioned between the plurality of twin-lead transmission lines.\",\n \"11.A method, comprising: receiving, by an antenna of a communication device, a respective electromagnetic wave of a plurality of electromagnetic waves, the respective electromagnetic wave guided by a respective cable pair of a bundle of cables, wherein the respective electromagnetic wave propagates without requiring an electrical return path; and obtaining, by the antenna from the respective electromagnetic wave, a respective communication signal of a plurality of communication signals conveyed by the plurality of electromagnetic waves.\",\n \"12.The method of claim 11, wherein the plurality of electromagnetic waves operates in a non-optical frequency range.\",\n \"13.The method of claim 11, wherein the bundle of cables comprises a plurality of twisted pairs of uninsulated conductors.\",\n \"14.The method of claim 11, wherein the bundle of cables comprises an insulated conductor, an uninsulated conductor, or combinations thereof.\",\n \"15.The method of claim 11, wherein the bundle of cables comprises a plurality of twisted pairs of insulated conductors.\",\n \"16.The method of claim 15, wherein the respective cable pair of the bundle of cables corresponds to a respective twisted pair of insulated conductors of the plurality of twisted pairs of insulated conductors.\",\n \"17.The method of claim 16, wherein each respective twisted pair of insulated conductors of the plurality of twisted pairs of insulated conductors has a respective electrical return path that enables transmission of electrical signals.\",\n \"18.The method of claim 11, wherein the plurality of electromagnetic waves employs phase shift keying, frequency shift keying, quadrature amplitude modulation, amplitude modulation, multi-carrier modulation, frequency division multiplexing, time division multiplexing, code division multiplexing, multiplexing via differing wave propagation modes, or any combinations thereof.\",\n \"19.A device, comprising: a spacer that facilitates separation of a plurality of transmission lines; and an antenna that facilitates receiving an electromagnetic wave of a plurality of electromagnetic waves, wherein each electromagnetic wave of the plurality of electromagnetic waves is guided by a different one of the plurality of transmission lines, wherein each electromagnetic wave of the plurality of electromagnetic waves propagates without requiring an electrical return path, and wherein the antenna is coupled to the spacer.\",\n \"20.The device of claim 19, wherein each electromagnetic wave of the plurality of electromagnetic waves conveys a different one of a plurality of communication signals.\"\n ],\n [\n \" BACKGROUND As smart phones and other portable devices increasingly become ubiquitous, and data usage increases, macrocell base station devices and existing wireless infrastructure in turn require higher bandwidth capability in order to address the increased demand.\",\n \"To provide additional mobile bandwidth, small cell deployment is being pursued, with microcells and picocells providing coverage for much smaller areas than traditional macrocells.\",\n \"In addition, most homes and businesses have grown to rely on broadband data access for services such as voice, video and Internet browsing, etc.\",\n \"Broadband access networks include satellite, 4G or 5G wireless, power line communication, fiber, cable, and telephone networks.\"\n ],\n [\n \" BRIEF DESCRIPTION OF THE DRAWINGS Reference will now be made to the accompanying drawings, which are not necessarily drawn to scale, and wherein: FIG.\",\n \"1 is a block diagram illustrating an example, non-limiting embodiment of a guided-wave communications system in accordance with various aspects described herein.\",\n \"FIG.\",\n \"2 is a block diagram illustrating an example, non-limiting embodiment of a transmission device in accordance with various aspects described herein.\",\n \"FIG.\",\n \"3 is a graphical diagram illustrating an example, non-limiting embodiment of an electromagnetic field distribution in accordance with various aspects described herein.\",\n \"FIG.\",\n \"4 is a graphical diagram illustrating an example, non-limiting embodiment of an electromagnetic field distribution in accordance with various aspects described herein.\",\n \"FIG.\",\n \"5A is a graphical diagram illustrating an example, non-limiting embodiment of a frequency response in accordance with various aspects described herein.\",\n \"FIG.\",\n \"5B is a graphical diagram illustrating example, non-limiting embodiments of a longitudinal cross-section of an insulated wire depicting fields of guided electromagnetic waves at various operating frequencies in accordance with various aspects described herein.\",\n \"FIG.\",\n \"6 is a graphical diagram illustrating an example, non-limiting embodiment of an electromagnetic field distribution in accordance with various aspects described herein.\",\n \"FIG.\",\n \"7 is a block diagram illustrating an example, non-limiting embodiment of an arc coupler in accordance with various aspects described herein.\",\n \"FIG.\",\n \"8 is a block diagram illustrating an example, non-limiting embodiment of an arc coupler in accordance with various aspects described herein.\",\n \"FIG.\",\n \"9A is a block diagram illustrating an example, non-limiting embodiment of a stub coupler in accordance with various aspects described herein.\",\n \"FIG.\",\n \"9B is a diagram illustrating an example, non-limiting embodiment of an electromagnetic distribution in accordance with various aspects described herein.\",\n \"FIGS.\",\n \"10A and 10B are block diagrams illustrating example, non-limiting embodiments of couplers and transceivers in accordance with various aspects described herein.\",\n \"FIG.\",\n \"11 is a block diagram illustrating an example, non-limiting embodiment of a dual stub coupler in accordance with various aspects described herein.\",\n \"FIG.\",\n \"12 is a block diagram illustrating an example, non-limiting embodiment of a repeater system in accordance with various aspects described herein.\",\n \"FIG.\",\n \"13 illustrates a block diagram illustrating an example, non-limiting embodiment of a bidirectional repeater in accordance with various aspects described herein.\",\n \"FIG.\",\n \"14 is a block diagram illustrating an example, non-limiting embodiment of a waveguide system in accordance with various aspects described herein.\",\n \"FIG.\",\n \"15 is a block diagram illustrating an example, non-limiting embodiment of a guided-wave communications system in accordance with various aspects described herein.\",\n \"FIGS.\",\n \"16A, 16B and 16C are block diagrams illustrating an example, non-limiting embodiment of a system for managing a communication system in accordance with various aspects described herein.\",\n \"FIG.\",\n \"16D illustrates a flow diagram of an example, non-limiting embodiment of a method in accordance with various aspects described herein.\",\n \"FIG.\",\n \"17A illustrates a flow diagram of an example, non-limiting embodiment of a method for detecting and mitigating disturbances occurring in a communication network of the system of FIGS.\",\n \"16A, 16B, and 16C .\",\n \"FIG.\",\n \"17B illustrates a flow diagram of an example, non-limiting embodiment of a method for detecting and mitigating disturbances occurring in a communication network of the system of FIGS.\",\n \"16A, 16B, and 16C .\",\n \"FIG.\",\n \"18 illustrates a block diagram illustrating an example, non-limiting embodiment of a cross-sectional view of transmission media in accordance with various aspects described herein.\",\n \"FIG.\",\n \"19 illustrates a block diagram illustrating an example, non-limiting embodiment of spacing device for coupling to the transmission media in accordance with various aspects described herein.\",\n \"FIG.\",\n \"20 illustrates a flow diagram of an example, non-limiting embodiment of a method in accordance with various aspects described herein.\",\n \"FIG.\",\n \"21 is a block diagram of an example, non-limiting embodiment of a computing environment in accordance with various aspects described herein.\",\n \"FIG.\",\n \"22 is a block diagram of an example, non-limiting embodiment of a mobile network platform in accordance with various aspects described herein.\",\n \"FIG.\",\n \"23 is a block diagram of an example, non-limiting embodiment of a communication device in accordance with various aspects described herein.\",\n \"detailed-description description=\\\"Detailed Description\\\" end=\\\"lead\\\"?\"\n ],\n [\n \"CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of U.S. patent application Ser.\",\n \"No.\",\n \"15/665,632, filed Aug. 1, 2017, which is a continuation of U.S. patent application Ser.\",\n \"No.\",\n \"15/250,345, filed Aug. 29, 2016, now U.S. Pat.\",\n \"No.\",\n \"9,838,078, which is a continuation of U.S. patent application Ser.\",\n \"No.\",\n \"14/815,019, filed Jul.\",\n \"31, 2015, now U.S. Pat.\",\n \"No.\",\n \"9,461,706.The contents of the foregoing are hereby incorporated by reference into this application as if set forth herein in full.\",\n \"FIELD OF THE DISCLOSURE The subject disclosure relates to guided electromagnetic wave communications.\",\n \"BACKGROUND As smart phones and other portable devices increasingly become ubiquitous, and data usage increases, macrocell base station devices and existing wireless infrastructure in turn require higher bandwidth capability in order to address the increased demand.\",\n \"To provide additional mobile bandwidth, small cell deployment is being pursued, with microcells and picocells providing coverage for much smaller areas than traditional macrocells.\",\n \"In addition, most homes and businesses have grown to rely on broadband data access for services such as voice, video and Internet browsing, etc.\",\n \"Broadband access networks include satellite, 4G or 5G wireless, power line communication, fiber, cable, and telephone networks.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS Reference will now be made to the accompanying drawings, which are not necessarily drawn to scale, and wherein: FIG.\",\n \"1 is a block diagram illustrating an example, non-limiting embodiment of a guided-wave communications system in accordance with various aspects described herein.\",\n \"FIG.\",\n \"2 is a block diagram illustrating an example, non-limiting embodiment of a transmission device in accordance with various aspects described herein.\",\n \"FIG.\",\n \"3 is a graphical diagram illustrating an example, non-limiting embodiment of an electromagnetic field distribution in accordance with various aspects described herein.\",\n \"FIG.\",\n \"4 is a graphical diagram illustrating an example, non-limiting embodiment of an electromagnetic field distribution in accordance with various aspects described herein.\",\n \"FIG.\",\n \"5A is a graphical diagram illustrating an example, non-limiting embodiment of a frequency response in accordance with various aspects described herein.\",\n \"FIG.\",\n \"5B is a graphical diagram illustrating example, non-limiting embodiments of a longitudinal cross-section of an insulated wire depicting fields of guided electromagnetic waves at various operating frequencies in accordance with various aspects described herein.\",\n \"FIG.\",\n \"6 is a graphical diagram illustrating an example, non-limiting embodiment of an electromagnetic field distribution in accordance with various aspects described herein.\",\n \"FIG.\",\n \"7 is a block diagram illustrating an example, non-limiting embodiment of an arc coupler in accordance with various aspects described herein.\",\n \"FIG.\",\n \"8 is a block diagram illustrating an example, non-limiting embodiment of an arc coupler in accordance with various aspects described herein.\",\n \"FIG.\",\n \"9A is a block diagram illustrating an example, non-limiting embodiment of a stub coupler in accordance with various aspects described herein.\",\n \"FIG.\",\n \"9B is a diagram illustrating an example, non-limiting embodiment of an electromagnetic distribution in accordance with various aspects described herein.\",\n \"FIGS.\",\n \"10A and 10B are block diagrams illustrating example, non-limiting embodiments of couplers and transceivers in accordance with various aspects described herein.\",\n \"FIG.\",\n \"11 is a block diagram illustrating an example, non-limiting embodiment of a dual stub coupler in accordance with various aspects described herein.\",\n \"FIG.\",\n \"12 is a block diagram illustrating an example, non-limiting embodiment of a repeater system in accordance with various aspects described herein.\",\n \"FIG.\",\n \"13 illustrates a block diagram illustrating an example, non-limiting embodiment of a bidirectional repeater in accordance with various aspects described herein.\",\n \"FIG.\",\n \"14 is a block diagram illustrating an example, non-limiting embodiment of a waveguide system in accordance with various aspects described herein.\",\n \"FIG.\",\n \"15 is a block diagram illustrating an example, non-limiting embodiment of a guided-wave communications system in accordance with various aspects described herein.\",\n \"FIGS.\",\n \"16A, 16B and 16C are block diagrams illustrating an example, non-limiting embodiment of a system for managing a communication system in accordance with various aspects described herein.\",\n \"FIG.\",\n \"16D illustrates a flow diagram of an example, non-limiting embodiment of a method in accordance with various aspects described herein.\",\n \"FIG.\",\n \"17A illustrates a flow diagram of an example, non-limiting embodiment of a method for detecting and mitigating disturbances occurring in a communication network of the system of FIGS.\",\n \"16A, 16B, and 16C.\",\n \"FIG.\",\n \"17B illustrates a flow diagram of an example, non-limiting embodiment of a method for detecting and mitigating disturbances occurring in a communication network of the system of FIGS.\",\n \"16A, 16B, and 16C.\",\n \"FIG.\",\n \"18 illustrates a block diagram illustrating an example, non-limiting embodiment of a cross-sectional view of transmission media in accordance with various aspects described herein.\",\n \"FIG.\",\n \"19 illustrates a block diagram illustrating an example, non-limiting embodiment of spacing device for coupling to the transmission media in accordance with various aspects described herein.\",\n \"FIG.\",\n \"20 illustrates a flow diagram of an example, non-limiting embodiment of a method in accordance with various aspects described herein.\",\n \"FIG.\",\n \"21 is a block diagram of an example, non-limiting embodiment of a computing environment in accordance with various aspects described herein.\",\n \"FIG.\",\n \"22 is a block diagram of an example, non-limiting embodiment of a mobile network platform in accordance with various aspects described herein.\",\n \"FIG.\",\n \"23 is a block diagram of an example, non-limiting embodiment of a communication device in accordance with various aspects described herein.\",\n \"DETAILED DESCRIPTION One or more embodiments are now described with reference to the drawings, wherein like reference numerals are used to refer to like elements throughout.\",\n \"In the following description, for purposes of explanation, numerous details are set forth in order to provide a thorough understanding of the various embodiments.\",\n \"It is evident, however, that the various embodiments can be practiced without these details (and without applying to any particular networked environment or standard).\",\n \"In an embodiment, a guided wave communication system is presented for sending and receiving communication signals such as data or other signaling via guided electromagnetic waves.\",\n \"The guided electromagnetic waves include, for example, surface waves or other electromagnetic waves that are bound to or guided by a transmission medium.\",\n \"It will be appreciated that a variety of transmission media can be utilized with guided wave communications without departing from example embodiments.\",\n \"Examples of such transmission media can include one or more of the following, either alone or in one or more combinations: wires, whether insulated or not, and whether single-stranded or multi-stranded; conductors of other shapes or configurations including wire bundles, cables, rods, rails, pipes; non-conductors such as dielectric pipes, rods, rails, or other dielectric members; combinations of conductors and dielectric materials; or other guided wave transmission media.\",\n \"The inducement of guided electromagnetic waves on a transmission medium can be independent of any electrical potential, charge or current that is injected or otherwise transmitted through the transmission medium as part of an electrical circuit.\",\n \"For example, in the case where the transmission medium is a wire, it is to be appreciated that while a small current in the wire may be formed in response to the propagation of the guided waves along the wire, this can be due to the propagation of the electromagnetic wave along the wire surface, and is not formed in response to electrical potential, charge or current that is injected into the wire as part of an electrical circuit.\",\n \"The electromagnetic waves traveling on the wire therefore do not require a circuit to propagate along the wire surface.\",\n \"The wire therefore is a single wire transmission line that is not part of a circuit.\",\n \"Also, in some embodiments, a wire is not necessary, and the electromagnetic waves can propagate along a single line transmission medium that is not a wire.\",\n \"More generally, “guided electromagnetic waves” or “guided waves” as described by the subject disclosure are affected by the presence of a physical object that is at least a part of the transmission medium (e.g., a bare wire or other conductor, a dielectric, an insulated wire, a conduit or other hollow element, a bundle of insulated wires that is coated, covered or surrounded by a dielectric or insulator or other wire bundle, or another form of solid, liquid or otherwise non-gaseous transmission medium) so as to be at least partially bound to or guided by the physical object and so as to propagate along a transmission path of the physical object.\",\n \"Such a physical object can operate as at least a part of a transmission medium that guides, by way of an interface of the transmission medium (e.g., an outer surface, inner surface, an interior portion between the outer and the inner surfaces or other boundary between elements of the transmission medium), the propagation of guided electromagnetic waves, which in turn can carry energy, data and/or other signals along the transmission path from a sending device to a receiving device.\",\n \"Unlike free space propagation of wireless signals such as unguided (or unbounded) electromagnetic waves that decrease in intensity inversely by the square of the distance traveled by the unguided electromagnetic waves, guided electromagnetic waves can propagate along a transmission medium with less loss in magnitude per unit distance than experienced by unguided electromagnetic waves.\",\n \"Unlike electrical signals, guided electromagnetic waves can propagate from a sending device to a receiving device without requiring a separate electrical return path between the sending device and the receiving device.\",\n \"As a consequence, guided electromagnetic waves can propagate from a sending device to a receiving device along a transmission medium having no conductive components (e.g., a dielectric strip), or via a transmission medium having no more than a single conductor (e.g., a single bare wire or insulated wire).\",\n \"Even if a transmission medium includes one or more conductive components and the guided electromagnetic waves propagating along the transmission medium generate currents that flow in the one or more conductive components in a direction of the guided electromagnetic waves, such guided electromagnetic waves can propagate along the transmission medium from a sending device to a receiving device without requiring a flow of opposing currents on an electrical return path between the sending device and the receiving device.\",\n \"In a non-limiting illustration, consider electrical systems that transmit and receive electrical signals between sending and receiving devices by way of conductive media.\",\n \"Such systems generally rely on electrically separate forward and return paths.\",\n \"For instance, consider a coaxial cable having a center conductor and a ground shield that are separated by an insulator.\",\n \"Typically, in an electrical system a first terminal of a sending (or receiving) device can be connected to the center conductor, and a second terminal of the sending (or receiving) device can be connected to the ground shield.\",\n \"If the sending device injects an electrical signal in the center conductor via the first terminal, the electrical signal will propagate along the center conductor causing forward currents in the center conductor, and return currents in the ground shield.\",\n \"The same conditions apply for a two terminal receiving device.\",\n \"In contrast, consider a guided wave communication system such as described in the subject disclosure, which can utilize different embodiments of a transmission medium (including among others a coaxial cable) for transmitting and receiving guided electromagnetic waves without an electrical return path.\",\n \"In one embodiment, for example, the guided wave communication system of the subject disclosure can be configured to induce guided electromagnetic waves that propagate along an outer surface of a coaxial cable.\",\n \"Although the guided electromagnetic waves will cause forward currents on the ground shield, the guided electromagnetic waves do not require return currents to enable the guided electromagnetic waves to propagate along the outer surface of the coaxial cable.\",\n \"The same can be said of other transmission media used by a guided wave communication system for the transmission and reception of guided electromagnetic waves.\",\n \"For example, guided electromagnetic waves induced by the guided wave communication system on an outer surface of a bare wire, or an insulated wire can propagate along the bare wire or the insulated bare wire without an electrical return path.\",\n \"Consequently, electrical systems that require two or more conductors for carrying forward and reverse currents on separate conductors to enable the propagation of electrical signals injected by a sending device are distinct from guided wave systems that induce guided electromagnetic waves on an interface of a transmission medium without the need of an electrical return path to enable the propagation of the guided electromagnetic waves along the interface of the transmission medium.\",\n \"It is further noted that guided electromagnetic waves as described in the subject disclosure can have an electromagnetic field structure that lies primarily or substantially outside of a transmission medium so as to be bound to or guided by the transmission medium and so as to propagate non-trivial distances on or along an outer surface of the transmission medium.\",\n \"In other embodiments, guided electromagnetic waves can have an electromagnetic field structure that lies primarily or substantially inside a transmission medium so as to be bound to or guided by the transmission medium and so as to propagate non-trivial distances within the transmission medium.\",\n \"In other embodiments, guided electromagnetic waves can have an electromagnetic field structure that lies partially inside and partially outside a transmission medium so as to be bound to or guided by the transmission medium and so as to propagate non-trivial distances along the transmission medium.\",\n \"The desired electronic field structure in an embodiment may vary based upon a variety of factors, including the desired transmission distance, the characteristics of the transmission medium itself, and environmental conditions/characteristics outside of the transmission medium (e.g., presence of rain, fog, atmospheric conditions, etc.).\",\n \"Various embodiments described herein relate to coupling devices, that can be referred to as “waveguide coupling devices”, “waveguide couplers” or more simply as “couplers”, “coupling devices” or “launchers” for launching and/or extracting guided electromagnetic waves to and from a transmission medium at millimeter-wave frequencies (e.g., 30 to 300 GHz), wherein the wavelength can be small compared to one or more dimensions of the coupling device and/or the transmission medium such as the circumference of a wire or other cross sectional dimension, or lower microwave frequencies such as 300 MHz to 30 GHz.\",\n \"Transmissions can be generated to propagate as waves guided by a coupling device, such as: a strip, arc or other length of dielectric material; a horn, monopole, rod, slot or other antenna; an array of antennas; a magnetic resonant cavity, or other resonant coupler; a coil, a strip line, a waveguide or other coupling device.\",\n \"In operation, the coupling device receives an electromagnetic wave from a transmitter or transmission medium.\",\n \"The electromagnetic field structure of the electromagnetic wave can be carried inside the coupling device, outside the coupling device or some combination thereof.\",\n \"When the coupling device is in close proximity to a transmission medium, at least a portion of an electromagnetic wave couples to or is bound to the transmission medium, and continues to propagate as guided electromagnetic waves.\",\n \"In a reciprocal fashion, a coupling device can extract guided waves from a transmission medium and transfer these electromagnetic waves to a receiver.\",\n \"According to an example embodiment, a surface wave is a type of guided wave that is guided by a surface of a transmission medium, such as an exterior or outer surface of the wire, or another surface of the wire that is adjacent to or exposed to another type of medium having different properties (e.g., dielectric properties).\",\n \"Indeed, in an example embodiment, a surface of the wire that guides a surface wave can represent a transitional surface between two different types of media.\",\n \"For example, in the case of a bare or uninsulated wire, the surface of the wire can be the outer or exterior conductive surface of the bare or uninsulated wire that is exposed to air or free space.\",\n \"As another example, in the case of insulated wire, the surface of the wire can be the conductive portion of the wire that meets the insulator portion of the wire, or can otherwise be the insulator surface of the wire that is exposed to air or free space, or can otherwise be any material region between the insulator surface of the wire and the conductive portion of the wire that meets the insulator portion of the wire, depending upon the relative differences in the properties (e.g., dielectric properties) of the insulator, air, and/or the conductor and further dependent on the frequency and propagation mode or modes of the guided wave.\",\n \"According to an example embodiment, the term “about” a wire or other transmission medium used in conjunction with a guided wave can include fundamental guided wave propagation modes such as a guided waves having a circular or substantially circular field distribution, a symmetrical electromagnetic field distribution (e.g., electric field, magnetic field, electromagnetic field, etc.)\",\n \"or other fundamental mode pattern at least partially around a wire or other transmission medium.\",\n \"In addition, when a guided wave propagates “about” a wire or other transmission medium, it can do so according to a guided wave propagation mode that includes not only the fundamental wave propagation modes (e.g., zero order modes), but additionally or alternatively non-fundamental wave propagation modes such as higher-order guided wave modes (e.g., 1st order modes, 2nd order modes, etc.\",\n \"), asymmetrical modes and/or other guided (e.g., surface) waves that have non-circular field distributions around a wire or other transmission medium.\",\n \"As used herein, the term “guided wave mode” refers to a guided wave propagation mode of a transmission medium, coupling device or other system component of a guided wave communication system.\",\n \"For example, such non-circular field distributions can be unilateral or multi-lateral with one or more axial lobes characterized by relatively higher field strength and/or one or more nulls or null regions characterized by relatively low-field strength, zero-field strength or substantially zero-field strength.\",\n \"Further, the field distribution can otherwise vary as a function of azimuthal orientation around the wire such that one or more angular regions around the wire have an electric or magnetic field strength (or combination thereof) that is higher than one or more other angular regions of azimuthal orientation, according to an example embodiment.\",\n \"It will be appreciated that the relative orientations or positions of the guided wave higher order modes or asymmetrical modes can vary as the guided wave travels along the wire.\",\n \"As used herein, the term “millimeter-wave” can refer to electromagnetic waves/signals that fall within the “millimeter-wave frequency band” of 30 GHz to 300 GHz.\",\n \"The term “microwave” can refer to electromagnetic waves/signals that fall within a “microwave frequency band” of 300 MHz to 300 GHz.\",\n \"The term “radio frequency” or “RF” can refer to electromagnetic waves/signals that fall within the “radio frequency band” of 10 kHz to 1 THz.\",\n \"It is appreciated that wireless signals, electrical signals, and guided electromagnetic waves as described in the subject disclosure can be configured to operate at any desirable frequency range, such as, for example, at frequencies within, above or below millimeter-wave and/or microwave frequency bands.\",\n \"In particular, when a coupling device or transmission medium includes a conductive element, the frequency of the guided electromagnetic waves that are carried by the coupling device and/or propagate along the transmission medium can be below the mean collision frequency of the electrons in the conductive element.\",\n \"Further, the frequency of the guided electromagnetic waves that are carried by the coupling device and/or propagate along the transmission medium can be a non-optical frequency, e.g., a radio frequency below the range of optical frequencies that begins at 1 THz.\",\n \"As used herein, the term “antenna” can refer to a device that is part of a transmitting or receiving system to transmit/radiate or receive wireless signals.\",\n \"In accordance with one or more embodiments, a method can include receiving, by each of a plurality of launchers, one of a plurality of communication signals, each of the plurality of communication signals including different data, and launching, by each of the plurality of launchers, one of a plurality of electromagnetic waves, each electromagnetic wave of the plurality of electromagnetic waves guided by one of a plurality of twin-lead transmission lines formed between different ones of a plurality of power lines and a common cable, and each electromagnetic wave of the plurality of electromagnetic waves including a different one of the plurality of communication signals.\",\n \"In accordance with one or more embodiments, a method can include receiving, by each of a plurality of receivers, one of a plurality of electromagnetic waves, each electromagnetic wave of the plurality of electromagnetic waves guided by a different one of a plurality of twin-lead transmission lines, each twin-lead transmission line sharing a wire, and each electromagnetic wave of the plurality of electromagnetic waves including a different one of a plurality of communication signals, and obtaining, by each of the plurality of receivers, one of the plurality of communication signals.\",\n \"In accordance with one or more embodiments, a device can include a spacer that facilitates separation of a plurality of power lines and a common cable, and a plurality of transmitters coupled to the spacer, each of the plurality of transmitters facilitating transmission of one of a plurality of electromagnetic waves, each electromagnetic wave of the plurality of electromagnetic waves guided by one of a plurality of twin-lead transmission lines formed between different ones of the plurality of power lines and the common cable.\",\n \"Referring now to FIG.\",\n \"1, a block diagram 100 illustrating an example, non-limiting embodiment of a guided wave communications system is shown.\",\n \"In operation, a transmission device 101 receives one or more communication signals 110 from a communication network or other communications device that includes data and generates guided waves 120 to convey the data via the transmission medium 125 to the transmission device 102.The transmission device 102 receives the guided waves 120 and converts them to communication signals 112 that include the data for transmission to a communications network or other communications device.\",\n \"The guided waves 120 can be modulated to convey data via a modulation technique such as phase shift keying, frequency shift keying, quadrature amplitude modulation, amplitude modulation, multi-carrier modulation such as orthogonal frequency division multiplexing and via multiple access techniques such as frequency division multiplexing, time division multiplexing, code division multiplexing, multiplexing via differing wave propagation modes and via other modulation and access strategies.\",\n \"The communication network or networks can include a wireless communication network such as a mobile data network, a cellular voice and data network, a wireless local area network (e.g., WiFi or an 802.xx network), a satellite communications network, a personal area network or other wireless network.\",\n \"The communication network or networks can also include a wired communication network such as a telephone network, an Ethernet network, a local area network, a wide area network such as the Internet, a broadband access network, a cable network, a fiber optic network, or other wired network.\",\n \"The communication devices can include a network edge device, bridge device or home gateway, a set-top box, broadband modem, telephone adapter, access point, base station, or other fixed communication device, a mobile communication device such as an automotive gateway or automobile, laptop computer, tablet, smartphone, cellular telephone, or other communication device.\",\n \"In an example embodiment, the guided wave communication system 100 can operate in a bi-directional fashion where transmission device 102 receives one or more communication signals 112 from a communication network or device that includes other data and generates guided waves 122 to convey the other data via the transmission medium 125 to the transmission device 101.In this mode of operation, the transmission device 101 receives the guided waves 122 and converts them to communication signals 110 that include the other data for transmission to a communications network or device.\",\n \"The guided waves 122 can be modulated to convey data via a modulation technique such as phase shift keying, frequency shift keying, quadrature amplitude modulation, amplitude modulation, multi-carrier modulation such as orthogonal frequency division multiplexing and via multiple access techniques such as frequency division multiplexing, time division multiplexing, code division multiplexing, multiplexing via differing wave propagation modes and via other modulation and access strategies.\",\n \"The transmission medium 125 can include a cable having at least one inner portion surrounded by a dielectric material such as an insulator or other dielectric cover, coating or other dielectric material, the dielectric material having an outer surface and a corresponding circumference.\",\n \"In an example embodiment, the transmission medium 125 operates as a single-wire transmission line to guide the transmission of an electromagnetic wave.\",\n \"When the transmission medium 125 is implemented as a single wire transmission system, it can include a wire.\",\n \"The wire can be insulated or uninsulated, and single-stranded or multi-stranded (e.g., braided).\",\n \"In other embodiments, the transmission medium 125 can contain conductors of other shapes or configurations including wire bundles, cables, rods, rails, pipes.\",\n \"In addition, the transmission medium 125 can include non-conductors such as dielectric pipes, rods, rails, or other dielectric members; combinations of conductors and dielectric materials, conductors without dielectric materials or other guided wave transmission media.\",\n \"It should be noted that the transmission medium 125 can otherwise include any of the transmission media previously discussed.\",\n \"Further, as previously discussed, the guided waves 120 and 122 can be contrasted with radio transmissions over free space/air or conventional propagation of electrical power or signals through the conductor of a wire via an electrical circuit.\",\n \"In addition to the propagation of guided waves 120 and 122, the transmission medium 125 may optionally contain one or more wires that propagate electrical power or other communication signals in a conventional manner as a part of one or more electrical circuits.\",\n \"Referring now to FIG.\",\n \"2, a block diagram 200 illustrating an example, non-limiting embodiment of a transmission device is shown.\",\n \"The transmission device 101 or 102 includes a communications interface (I/F) 205, a transceiver 210 and a coupler 220.In an example of operation, the communications interface 205 receives a communication signal 110 or 112 that includes data.\",\n \"In various embodiments, the communications interface 205 can include a wireless interface for receiving a wireless communication signal in accordance with a wireless standard protocol such as LTE or other cellular voice and data protocol, WiFi or an 802.11 protocol, WIMAX protocol, Ultra Wideband protocol, Bluetooth protocol, Zigbee protocol, a direct broadcast satellite (DBS) or other satellite communication protocol or other wireless protocol.\",\n \"In addition or in the alternative, the communications interface 205 includes a wired interface that operates in accordance with an Ethernet protocol, universal serial bus (USB) protocol, a data over cable service interface specification (DOCSIS) protocol, a digital subscriber line (DSL) protocol, a Firewire (IEEE 1394) protocol, or other wired protocol.\",\n \"In additional to standards-based protocols, the communications interface 205 can operate in conjunction with other wired or wireless protocol.\",\n \"In addition, the communications interface 205 can optionally operate in conjunction with a protocol stack that includes multiple protocol layers including a MAC protocol, transport protocol, application protocol, etc.\",\n \"In an example of operation, the transceiver 210 generates an electromagnetic wave based on the communication signal 110 or 112 to convey the data.\",\n \"The electromagnetic wave has at least one carrier frequency and at least one corresponding wavelength.\",\n \"The carrier frequency can be within a millimeter-wave frequency band of 30 GHz-300 GHz, such as 60 GHz or a carrier frequency in the range of 30-40 GHz or a lower frequency band of 300 MHz-30 GHz in the microwave frequency range such as 26-30 GHz, 11 GHz, 6 GHz or 3 GHz, but it will be appreciated that other carrier frequencies are possible in other embodiments.\",\n \"In one mode of operation, the transceiver 210 merely upconverts the communications signal or signals 110 or 112 for transmission of the electromagnetic signal in the microwave or millimeter-wave band as a guided electromagnetic wave that is guided by or bound to the transmission medium 125.In another mode of operation, the communications interface 205 either converts the communication signal 110 or 112 to a baseband or near baseband signal or extracts the data from the communication signal 110 or 112 and the transceiver 210 modulates a high-frequency carrier with the data, the baseband or near baseband signal for transmission.\",\n \"It should be appreciated that the transceiver 210 can modulate the data received via the communication signal 110 or 112 to preserve one or more data communication protocols of the communication signal 110 or 112 either by encapsulation in the payload of a different protocol or by simple frequency shifting.\",\n \"In the alternative, the transceiver 210 can otherwise translate the data received via the communication signal 110 or 112 to a protocol that is different from the data communication protocol or protocols of the communication signal 110 or 112.In an example of operation, the coupler 220 couples the electromagnetic wave to the transmission medium 125 as a guided electromagnetic wave to convey the communications signal or signals 110 or 112.While the prior description has focused on the operation of the transceiver 210 as a transmitter, the transceiver 210 can also operate to receive electromagnetic waves that convey other data from the single wire transmission medium via the coupler 220 and to generate communications signals 110 or 112, via communications interface 205 that includes the other data.\",\n \"Consider embodiments where an additional guided electromagnetic wave conveys other data that also propagates along the transmission medium 125.The coupler 220 can also couple this additional electromagnetic wave from the transmission medium 125 to the transceiver 210 for reception.\",\n \"The transmission device 101 or 102 includes an optional training controller 230.In an example embodiment, the training controller 230 is implemented by a standalone processor or a processor that is shared with one or more other components of the transmission device 101 or 102.The training controller 230 selects the carrier frequencies, modulation schemes and/or guided wave modes for the guided electromagnetic waves based on feedback data received by the transceiver 210 from at least one remote transmission device coupled to receive the guided electromagnetic wave.\",\n \"In an example embodiment, a guided electromagnetic wave transmitted by a remote transmission device 101 or 102 conveys data that also propagates along the transmission medium 125.The data from the remote transmission device 101 or 102 can be generated to include the feedback data.\",\n \"In operation, the coupler 220 also couples the guided electromagnetic wave from the transmission medium 125 and the transceiver receives the electromagnetic wave and processes the electromagnetic wave to extract the feedback data.\",\n \"In an example embodiment, the training controller 230 operates based on the feedback data to evaluate a plurality of candidate frequencies, modulation schemes and/or transmission modes to select a carrier frequency, modulation scheme and/or transmission mode to enhance performance, such as throughput, signal strength, reduce propagation loss, etc.\",\n \"Consider the following example: a transmission device 101 begins operation under control of the training controller 230 by sending a plurality of guided waves as test signals such as pilot waves or other test signals at a corresponding plurality of candidate frequencies and/or candidate modes directed to a remote transmission device 102 coupled to the transmission medium 125.The guided waves can include, in addition or in the alternative, test data.\",\n \"The test data can indicate the particular candidate frequency and/or guide-wave mode of the signal.\",\n \"In an embodiment, the training controller 230 at the remote transmission device 102 receives the test signals and/or test data from any of the guided waves that were properly received and determines the best candidate frequency and/or guided wave mode, a set of acceptable candidate frequencies and/or guided wave modes, or a rank ordering of candidate frequencies and/or guided wave modes.\",\n \"This selection of candidate frequenc(ies) or/and guided-mode(s) are generated by the training controller 230 based on one or more optimizing criteria such as received signal strength, bit error rate, packet error rate, signal to noise ratio, propagation loss, etc.\",\n \"The training controller 230 generates feedback data that indicates the selection of candidate frequenc(ies) or/and guided wave mode(s) and sends the feedback data to the transceiver 210 for transmission to the transmission device 101.The transmission device 101 and 102 can then communicate data with one another based on the selection of candidate frequenc(ies) or/and guided wave mode(s).\",\n \"In other embodiments, the guided electromagnetic waves that contain the test signals and/or test data are reflected back, repeated back or otherwise looped back by the remote transmission device 102 to the transmission device 101 for reception and analysis by the training controller 230 of the transmission device 101 that initiated these waves.\",\n \"For example, the transmission device 101 can send a signal to the remote transmission device 102 to initiate a test mode where a physical reflector is switched on the line, a termination impedance is changed to cause reflections, a loop back mode is switched on to couple electromagnetic waves back to the source transmission device 102, and/or a repeater mode is enabled to amplify and retransmit the electromagnetic waves back to the source transmission device 102.The training controller 230 at the source transmission device 102 receives the test signals and/or test data from any of the guided waves that were properly received and determines selection of candidate frequenc(ies) or/and guided wave mode(s).\",\n \"While the procedure above has been described in a start-up or initialization mode of operation, each transmission device 101 or 102 can send test signals, evaluate candidate frequencies or guided wave modes via non-test such as normal transmissions or otherwise evaluate candidate frequencies or guided wave modes at other times or continuously as well.\",\n \"In an example embodiment, the communication protocol between the transmission devices 101 and 102 can include an on-request or periodic test mode where either full testing or more limited testing of a subset of candidate frequencies and guided wave modes are tested and evaluated.\",\n \"In other modes of operation, the re-entry into such a test mode can be triggered by a degradation of performance due to a disturbance, weather conditions, etc.\",\n \"In an example embodiment, the receiver bandwidth of the transceiver 210 is either sufficiently wide or swept to receive all candidate frequencies or can be selectively adjusted by the training controller 230 to a training mode where the receiver bandwidth of the transceiver 210 is sufficiently wide or swept to receive all candidate frequencies.\",\n \"Referring now to FIG.\",\n \"3, a graphical diagram 300 illustrating an example, non-limiting embodiment of an electromagnetic field distribution is shown.\",\n \"In this embodiment, a transmission medium 125 in air includes an inner conductor 301 and an insulating jacket 302 of dielectric material, as shown in cross section.\",\n \"The diagram 300 includes different gray-scales that represent differing electromagnetic field strengths generated by the propagation of the guided wave having an asymmetrical and non-fundamental guided wave mode.\",\n \"In particular, the electromagnetic field distribution corresponds to a modal “sweet spot” that enhances guided electromagnetic wave propagation along an insulated transmission medium and reduces end-to-end transmission loss.\",\n \"In this particular mode, electromagnetic waves are guided by the transmission medium 125 to propagate along an outer surface of the transmission medium—in this case, the outer surface of the insulating jacket 302.Electromagnetic waves are partially embedded in the insulator and partially radiating on the outer surface of the insulator.\",\n \"In this fashion, electromagnetic waves are “lightly” coupled to the insulator so as to enable electromagnetic wave propagation at long distances with low propagation loss.\",\n \"As shown, the guided wave has a field structure that lies primarily or substantially outside of the transmission medium 125 that serves to guide the electromagnetic waves.\",\n \"The regions inside the conductor 301 have little or no field.\",\n \"Likewise regions inside the insulating jacket 302 have low field strength.\",\n \"The majority of the electromagnetic field strength is distributed in the lobes 304 at the outer surface of the insulating jacket 302 and in close proximity thereof.\",\n \"The presence of an asymmetric guided wave mode is shown by the high electromagnetic field strengths at the top and bottom of the outer surface of the insulating jacket 302 (in the orientation of the diagram)—as opposed to very small field strengths on the other sides of the insulating jacket 302.The example shown corresponds to a 38 GHz electromagnetic wave guided by a wire with a diameter of 1.1 cm and a dielectric insulation of thickness of 0.36 cm.\",\n \"Because the electromagnetic wave is guided by the transmission medium 125 and the majority of the field strength is concentrated in the air outside of the insulating jacket 302 within a limited distance of the outer surface, the guided wave can propagate longitudinally down the transmission medium 125 with very low loss.\",\n \"In the example shown, this “limited distance” corresponds to a distance from the outer surface that is less than half the largest cross sectional dimension of the transmission medium 125.In this case, the largest cross sectional dimension of the wire corresponds to the overall diameter of 1.82 cm, however, this value can vary with the size and shape of the transmission medium 125.For example, should the transmission medium 125 be of a rectangular shape with a height of 0.3 cm and a width of 0.4 cm, the largest cross sectional dimension would be the diagonal of 0.5 cm and the corresponding limited distance would be 0.25 cm.\",\n \"The dimensions of the area containing the majority of the field strength also vary with the frequency, and in general, increase as carrier frequencies decrease.\",\n \"It should also be noted that the components of a guided wave communication system, such as couplers and transmission media can have their own cut-off frequencies for each guided wave mode.\",\n \"The cut-off frequency generally sets forth the lowest frequency that a particular guided wave mode is designed to be supported by that particular component.\",\n \"In an example embodiment, the particular asymmetric mode of propagation shown is induced on the transmission medium 125 by an electromagnetic wave having a frequency that falls within a limited range (such as Fc to 2Fc) of the lower cut-off frequency Fc for this particular asymmetric mode.\",\n \"The lower cut-off frequency Fc is particular to the characteristics of transmission medium 125.For embodiments as shown that include an inner conductor 301 surrounded by an insulating jacket 302, this cutoff frequency can vary based on the dimensions and properties of the insulating jacket 302 and potentially the dimensions and properties of the inner conductor 301 and can be determined experimentally to have a desired mode pattern.\",\n \"It should be noted however, that similar effects can be found for a hollow dielectric or insulator without an inner conductor.\",\n \"In this case, the cutoff frequency can vary based on the dimensions and properties of the hollow dielectric or insulator.\",\n \"At frequencies lower than the lower cut-off frequency, the asymmetric mode is difficult to induce in the transmission medium 125 and fails to propagate for all but trivial distances.\",\n \"As the frequency increases above the limited range of frequencies about the cut-off frequency, the asymmetric mode shifts more and more inward of the insulating jacket 302.At frequencies much larger than the cut-off frequency, the field strength is no longer concentrated outside of the insulating jacket, but primarily inside of the insulating jacket 302.While the transmission medium 125 provides strong guidance to the electromagnetic wave and propagation is still possible, ranges are more limited by increased losses due to propagation within the insulating jacket 302—as opposed to the surrounding air.\",\n \"Referring now to FIG.\",\n \"4, a graphical diagram 400 illustrating an example, non-limiting embodiment of an electromagnetic field distribution is shown.\",\n \"In particular, a cross section diagram 400, similar to FIG.\",\n \"3 is shown with common reference numerals used to refer to similar elements.\",\n \"The example shown corresponds to a 60 GHz wave guided by a wire with a diameter of 1.1 cm and a dielectric insulation of thickness of 0.36 cm.\",\n \"Because the frequency of the guided wave is above the limited range of the cut-off frequency of this particular asymmetric mode, much of the field strength has shifted inward of the insulating jacket 302.In particular, the field strength is concentrated primarily inside of the insulating jacket 302.While the transmission medium 125 provides strong guidance to the electromagnetic wave and propagation is still possible, ranges are more limited when compared with the embodiment of FIG.\",\n \"3, by increased losses due to propagation within the insulating jacket 302.Referring now to FIG.\",\n \"5A, a graphical diagram illustrating an example, non-limiting embodiment of a frequency response is shown.\",\n \"In particular, diagram 500 presents a graph of end-to-end loss (in dB) as a function of frequency, overlaid with electromagnetic field distributions 510, 520 and 530 at three points for a 200 cm insulated medium voltage wire.\",\n \"The boundary between the insulator and the surrounding air is represented by reference numeral 525 in each electromagnetic field distribution.\",\n \"As discussed in conjunction with FIG.\",\n \"3, an example of a desired asymmetric mode of propagation shown is induced on the transmission medium 125 by an electromagnetic wave having a frequency that falls within a limited range (such as Fc to 2Fc) of the lower cut-off frequency Fc of the transmission medium for this particular asymmetric mode.\",\n \"In particular, the electromagnetic field distribution 520 at 6 GHz falls within this modal “sweet spot” that enhances electromagnetic wave propagation along an insulated transmission medium and reduces end-to-end transmission loss.\",\n \"In this particular mode, guided waves are partially embedded in the insulator and partially radiating on the outer surface of the insulator.\",\n \"In this fashion, the electromagnetic waves are “lightly” coupled to the insulator so as to enable guided electromagnetic wave propagation at long distances with low propagation loss.\",\n \"At lower frequencies represented by the electromagnetic field distribution 510 at 3 GHz, the asymmetric mode radiates more heavily generating higher propagation losses.\",\n \"At higher frequencies represented by the electromagnetic field distribution 530 at 9 GHz, the asymmetric mode shifts more and more inward of the insulating jacket providing too much absorption, again generating higher propagation losses.\",\n \"Referring now to FIG.\",\n \"5B, a graphical diagram 550 illustrating example, non-limiting embodiments of a longitudinal cross-section of a transmission medium 125, such as an insulated wire, depicting fields of guided electromagnetic waves at various operating frequencies is shown.\",\n \"As shown in diagram 556, when the guided electromagnetic waves are at approximately the cutoff frequency (fc) corresponding to the modal “sweet spot”, the guided electromagnetic waves are loosely coupled to the insulated wire so that absorption is reduced, and the fields of the guided electromagnetic waves are bound sufficiently to reduce the amount radiated into the environment (e.g., air).\",\n \"Because absorption and radiation of the fields of the guided electromagnetic waves is low, propagation losses are consequently low, enabling the guided electromagnetic waves to propagate for longer distances.\",\n \"As shown in diagram 554, propagation losses increase when an operating frequency of the guide electromagnetic waves increases above about two-times the cutoff frequency (fc)—or as referred to, above the range of the “sweet spot”.\",\n \"More of the field strength of the electromagnetic wave is driven inside the insulating layer, increasing propagation losses.\",\n \"At frequencies much higher than the cutoff frequency (fc) the guided electromagnetic waves are strongly bound to the insulated wire as a result of the fields emitted by the guided electromagnetic waves being concentrated in the insulation layer of the wire, as shown in diagram 552.This in turn raises propagation losses further due to absorption of the guided electromagnetic waves by the insulation layer.\",\n \"Similarly, propagation losses increase when the operating frequency of the guided electromagnetic waves is substantially below the cutoff frequency (fc), as shown in diagram 558.At frequencies much lower than the cutoff frequency (fc) the guided electromagnetic waves are weakly (or nominally) bound to the insulated wire and thereby tend to radiate into the environment (e.g., air), which in turn, raises propagation losses due to radiation of the guided electromagnetic waves.\",\n \"Referring now to FIG.\",\n \"6, a graphical diagram 600 illustrating an example, non-limiting embodiment of an electromagnetic field distribution is shown.\",\n \"In this embodiment, a transmission medium 602 is a bare wire, as shown in cross section.\",\n \"The diagram 300 includes different gray-scales that represent differing electromagnetic field strengths generated by the propagation of a guided wave having a symmetrical and fundamental guided wave mode at a single carrier frequency.\",\n \"In this particular mode, electromagnetic waves are guided by the transmission medium 602 to propagate along an outer surface of the transmission medium—in this case, the outer surface of the bare wire.\",\n \"Electromagnetic waves are “lightly” coupled to the wire so as to enable electromagnetic wave propagation at long distances with low propagation loss.\",\n \"As shown, the guided wave has a field structure that lies substantially outside of the transmission medium 602 that serves to guide the electromagnetic waves.\",\n \"The regions inside the conductor 602 have little or no field.\",\n \"Referring now to FIG.\",\n \"7, a block diagram 700 illustrating an example, non-limiting embodiment of an arc coupler is shown.\",\n \"In particular a coupling device is presented for use in a transmission device, such as transmission device 101 or 102 presented in conjunction with FIG.\",\n \"1.The coupling device includes an arc coupler 704 coupled to a transmitter circuit 712 and termination or damper 714.The arc coupler 704 can be made of a dielectric material, or other low-loss insulator (e.g., Teflon, polyethylene, etc.\",\n \"), or made of a conducting (e.g., metallic, non-metallic, etc.)\",\n \"material, or any combination of the foregoing materials.\",\n \"As shown, the arc coupler 704 operates as a waveguide and has a wave 706 propagating as a guided wave about a waveguide surface of the arc coupler 704.In the embodiment shown, at least a portion of the arc coupler 704 can be placed near a wire 702 or other transmission medium, (such as transmission medium 125), in order to facilitate coupling between the arc coupler 704 and the wire 702 or other transmission medium, as described herein to launch the guided wave 708 on the wire.\",\n \"The arc coupler 704 can be placed such that a portion of the curved arc coupler 704 is tangential to, and parallel or substantially parallel to the wire 702.The portion of the arc coupler 704 that is parallel to the wire can be an apex of the curve, or any point where a tangent of the curve is parallel to the wire 702.When the arc coupler 704 is positioned or placed thusly, the wave 706 travelling along the arc coupler 704 couples, at least in part, to the wire 702, and propagates as guided wave 708 around or about the wire surface of the wire 702 and longitudinally along the wire 702.The guided wave 708 can be characterized as a surface wave or other electromagnetic wave that is guided by or bound to the wire 702 or other transmission medium.\",\n \"A portion of the wave 706 that does not couple to the wire 702 propagates as a wave 710 along the arc coupler 704.It will be appreciated that the arc coupler 704 can be configured and arranged in a variety of positions in relation to the wire 702 to achieve a desired level of coupling or non-coupling of the wave 706 to the wire 702.For example, the curvature and/or length of the arc coupler 704 that is parallel or substantially parallel, as well as its separation distance (which can include zero separation distance in an embodiment), to the wire 702 can be varied without departing from example embodiments.\",\n \"Likewise, the arrangement of arc coupler 704 in relation to the wire 702 may be varied based upon considerations of the respective intrinsic characteristics (e.g., thickness, composition, electromagnetic properties, etc.)\",\n \"of the wire 702 and the arc coupler 704, as well as the characteristics (e.g., frequency, energy level, etc.)\",\n \"of the waves 706 and 708.The guided wave 708 stays parallel or substantially parallel to the wire 702, even as the wire 702 bends and flexes.\",\n \"Bends in the wire 702 can increase transmission losses, which are also dependent on wire diameters, frequency, and materials.\",\n \"If the dimensions of the arc coupler 704 are chosen for efficient power transfer, most of the power in the wave 706 is transferred to the wire 702, with little power remaining in wave 710.It will be appreciated that the guided wave 708 can still be multi-modal in nature (discussed herein), including having modes that are non-fundamental or asymmetric, while traveling along a path that is parallel or substantially parallel to the wire 702, with or without a fundamental transmission mode.\",\n \"In an embodiment, non-fundamental or asymmetric modes can be utilized to minimize transmission losses and/or obtain increased propagation distances.\",\n \"It is noted that the term parallel is generally a geometric construct which often is not exactly achievable in real systems.\",\n \"Accordingly, the term parallel as utilized in the subject disclosure represents an approximation rather than an exact configuration when used to describe embodiments disclosed in the subject disclosure.\",\n \"In an embodiment, substantially parallel can include approximations that are within 30 degrees of true parallel in all dimensions.\",\n \"In an embodiment, the wave 706 can exhibit one or more wave propagation modes.\",\n \"The arc coupler modes can be dependent on the shape and/or design of the coupler 704.The one or more arc coupler modes of wave 706 can generate, influence, or impact one or more wave propagation modes of the guided wave 708 propagating along wire 702.It should be particularly noted however that the guided wave modes present in the guided wave 706 may be the same or different from the guided wave modes of the guided wave 708.In this fashion, one or more guided wave modes of the guided wave 706 may not be transferred to the guided wave 708, and further one or more guided wave modes of guided wave 708 may not have been present in guided wave 706.It should also be noted that the cut-off frequency of the arc coupler 704 for a particular guided wave mode may be different than the cutoff frequency of the wire 702 or other transmission medium for that same mode.\",\n \"For example, while the wire 702 or other transmission medium may be operated slightly above its cutoff frequency for a particular guided wave mode, the arc coupler 704 may be operated well above its cut-off frequency for that same mode for low loss, slightly below its cut-off frequency for that same mode to, for example, induce greater coupling and power transfer, or some other point in relation to the arc coupler's cutoff frequency for that mode.\",\n \"In an embodiment, the wave propagation modes on the wire 702 can be similar to the arc coupler modes since both waves 706 and 708 propagate about the outside of the arc coupler 704 and wire 702 respectively.\",\n \"In some embodiments, as the wave 706 couples to the wire 702, the modes can change form, or new modes can be created or generated, due to the coupling between the arc coupler 704 and the wire 702.For example, differences in size, material, and/or impedances of the arc coupler 704 and wire 702 may create additional modes not present in the arc coupler modes and/or suppress some of the arc coupler modes.\",\n \"The wave propagation modes can comprise the fundamental transverse electromagnetic mode (Quasi-TEM00), where only small electric and/or magnetic fields extend in the direction of propagation, and the electric and magnetic fields extend radially outwards while the guided wave propagates along the wire.\",\n \"This guided wave mode can be donut shaped, where few of the electromagnetic fields exist within the arc coupler 704 or wire 702.Waves 706 and 708 can comprise a fundamental TEM mode where the fields extend radially outwards, and also comprise other, non-fundamental (e.g., asymmetric, higher-level, etc.)\",\n \"modes.\",\n \"While particular wave propagation modes are discussed above, other wave propagation modes are likewise possible such as transverse electric (TE) and transverse magnetic (TM) modes, based on the frequencies employed, the design of the arc coupler 704, the dimensions and composition of the wire 702, as well as its surface characteristics, its insulation if present, the electromagnetic properties of the surrounding environment, etc.\",\n \"It should be noted that, depending on the frequency, the electrical and physical characteristics of the wire 702 and the particular wave propagation modes that are generated, guided wave 708 can travel along the conductive surface of an oxidized uninsulated wire, an unoxidized uninsulated wire, an insulated wire and/or along the insulating surface of an insulated wire.\",\n \"In an embodiment, a diameter of the arc coupler 704 is smaller than the diameter of the wire 702.For the millimeter-band wavelength being used, the arc coupler 704 supports a single waveguide mode that makes up wave 706.This single waveguide mode can change as it couples to the wire 702 as guided wave 708.If the arc coupler 704 were larger, more than one waveguide mode can be supported, but these additional waveguide modes may not couple to the wire 702 as efficiently, and higher coupling losses can result.\",\n \"However, in some alternative embodiments, the diameter of the arc coupler 704 can be equal to or larger than the diameter of the wire 702, for example, where higher coupling losses are desirable or when used in conjunction with other techniques to otherwise reduce coupling losses (e.g., impedance matching with tapering, etc.).\",\n \"In an embodiment, the wavelength of the waves 706 and 708 are comparable in size, or smaller than a circumference of the arc coupler 704 and the wire 702.In an example, if the wire 702 has a diameter of 0.5 cm, and a corresponding circumference of around 1.5 cm, the wavelength of the transmission is around 1.5 cm or less, corresponding to a frequency of 70 GHz or greater.\",\n \"In another embodiment, a suitable frequency of the transmission and the carrier-wave signal is in the range of 30-100 GHz, perhaps around 30-60 GHz, and around 38 GHz in one example.\",\n \"In an embodiment, when the circumference of the arc coupler 704 and wire 702 is comparable in size to, or greater, than a wavelength of the transmission, the waves 706 and 708 can exhibit multiple wave propagation modes including fundamental and/or non-fundamental (symmetric and/or asymmetric) modes that propagate over sufficient distances to support various communication systems described herein.\",\n \"The waves 706 and 708 can therefore comprise more than one type of electric and magnetic field configuration.\",\n \"In an embodiment, as the guided wave 708 propagates down the wire 702, the electrical and magnetic field configurations will remain the same from end to end of the wire 702.In other embodiments, as the guided wave 708 encounters interference (distortion or obstructions) or loses energy due to transmission losses or scattering, the electric and magnetic field configurations can change as the guided wave 708 propagates down wire 702.In an embodiment, the arc coupler 704 can be composed of nylon, Teflon, polyethylene, a polyamide, or other plastics.\",\n \"In other embodiments, other dielectric materials are possible.\",\n \"The wire surface of wire 702 can be metallic with either a bare metallic surface, or can be insulated using plastic, dielectric, insulator or other coating, jacket or sheathing.\",\n \"In an embodiment, a dielectric or otherwise non-conducting/insulated waveguide can be paired with either a bare/metallic wire or insulated wire.\",\n \"In other embodiments, a metallic and/or conductive waveguide can be paired with a bare/metallic wire or insulated wire.\",\n \"In an embodiment, an oxidation layer on the bare metallic surface of the wire 702 (e.g., resulting from exposure of the bare metallic surface to oxygen/air) can also provide insulating or dielectric properties similar to those provided by some insulators or sheathings.\",\n \"It is noted that the graphical representations of waves 706, 708 and 710 are presented merely to illustrate the principles that wave 706 induces or otherwise launches a guided wave 708 on a wire 702 that operates, for example, as a single wire transmission line.\",\n \"Wave 710 represents the portion of wave 706 that remains on the arc coupler 704 after the generation of guided wave 708.The actual electric and magnetic fields generated as a result of such wave propagation may vary depending on the frequencies employed, the particular wave propagation mode or modes, the design of the arc coupler 704, the dimensions and composition of the wire 702, as well as its surface characteristics, its optional insulation, the electromagnetic properties of the surrounding environment, etc.\",\n \"It is noted that arc coupler 704 can include a termination circuit or damper 714 at the end of the arc coupler 704 that can absorb leftover radiation or energy from wave 710.The termination circuit or damper 714 can prevent and/or minimize the leftover radiation or energy from wave 710 reflecting back toward transmitter circuit 712.In an embodiment, the termination circuit or damper 714 can include termination resistors, and/or other components that perform impedance matching to attenuate reflection.\",\n \"In some embodiments, if the coupling efficiencies are high enough, and/or wave 710 is sufficiently small, it may not be necessary to use a termination circuit or damper 714.For the sake of simplicity, these transmitter 712 and termination circuits or dampers 714 may not be depicted in the other figures, but in those embodiments, transmitter and termination circuits or dampers may possibly be used.\",\n \"Further, while a single arc coupler 704 is presented that generates a single guided wave 708, multiple arc couplers 704 placed at different points along the wire 702 and/or at different azimuthal orientations about the wire can be employed to generate and receive multiple guided waves 708 at the same or different frequencies, at the same or different phases, at the same or different wave propagation modes.\",\n \"FIG.\",\n \"8, a block diagram 800 illustrating an example, non-limiting embodiment of an arc coupler is shown.\",\n \"In the embodiment shown, at least a portion of the coupler 704 can be placed near a wire 702 or other transmission medium, (such as transmission medium 125), in order to facilitate coupling between the arc coupler 704 and the wire 702 or other transmission medium, to extract a portion of the guided wave 806 as a guided wave 808 as described herein.\",\n \"The arc coupler 704 can be placed such that a portion of the curved arc coupler 704 is tangential to, and parallel or substantially parallel to the wire 702.The portion of the arc coupler 704 that is parallel to the wire can be an apex of the curve, or any point where a tangent of the curve is parallel to the wire 702.When the arc coupler 704 is positioned or placed thusly, the wave 806 travelling along the wire 702 couples, at least in part, to the arc coupler 704, and propagates as guided wave 808 along the arc coupler 704 to a receiving device (not expressly shown).\",\n \"A portion of the wave 806 that does not couple to the arc coupler propagates as wave 810 along the wire 702 or other transmission medium.\",\n \"In an embodiment, the wave 806 can exhibit one or more wave propagation modes.\",\n \"The arc coupler modes can be dependent on the shape and/or design of the coupler 704.The one or more modes of guided wave 806 can generate, influence, or impact one or more guide-wave modes of the guided wave 808 propagating along the arc coupler 704.It should be particularly noted however that the guided wave modes present in the guided wave 806 may be the same or different from the guided wave modes of the guided wave 808.In this fashion, one or more guided wave modes of the guided wave 806 may not be transferred to the guided wave 808, and further one or more guided wave modes of guided wave 808 may not have been present in guided wave 806.Referring now to FIG.\",\n \"9A, a block diagram 900 illustrating an example, non-limiting embodiment of a stub coupler is shown.\",\n \"In particular a coupling device that includes stub coupler 904 is presented for use in a transmission device, such as transmission device 101 or 102 presented in conjunction with FIG.\",\n \"1.The stub coupler 904 can be made of a dielectric material, or other low-loss insulator (e.g., Teflon, polyethylene and etc.\",\n \"), or made of a conducting (e.g., metallic, non-metallic, etc.)\",\n \"material, or any combination of the foregoing materials.\",\n \"As shown, the stub coupler 904 operates as a waveguide and has a wave 906 propagating as a guided wave about a waveguide surface of the stub coupler 904.In the embodiment shown, at least a portion of the stub coupler 904 can be placed near a wire 702 or other transmission medium, (such as transmission medium 125), in order to facilitate coupling between the stub coupler 904 and the wire 702 or other transmission medium, as described herein to launch the guided wave 908 on the wire.\",\n \"In an embodiment, the stub coupler 904 is curved, and an end of the stub coupler 904 can be tied, fastened, or otherwise mechanically coupled to a wire 702.When the end of the stub coupler 904 is fastened to the wire 702, the end of the stub coupler 904 is parallel or substantially parallel to the wire 702.Alternatively, another portion of the dielectric waveguide beyond an end can be fastened or coupled to wire 702 such that the fastened or coupled portion is parallel or substantially parallel to the wire 702.The fastener 910 can be a nylon cable tie or other type of non-conducting/dielectric material that is either separate from the stub coupler 904 or constructed as an integrated component of the stub coupler 904.The stub coupler 904 can be adjacent to the wire 702 without surrounding the wire 702.Like the arc coupler 704 described in conjunction with FIG.\",\n \"7, when the stub coupler 904 is placed with the end parallel to the wire 702, the guided wave 906 travelling along the stub coupler 904 couples to the wire 702, and propagates as guided wave 908 about the wire surface of the wire 702.In an example embodiment, the guided wave 908 can be characterized as a surface wave or other electromagnetic wave.\",\n \"It is noted that the graphical representations of waves 906 and 908 are presented merely to illustrate the principles that wave 906 induces or otherwise launches a guided wave 908 on a wire 702 that operates, for example, as a single wire transmission line.\",\n \"The actual electric and magnetic fields generated as a result of such wave propagation may vary depending on one or more of the shape and/or design of the coupler, the relative position of the dielectric waveguide to the wire, the frequencies employed, the design of the stub coupler 904, the dimensions and composition of the wire 702, as well as its surface characteristics, its optional insulation, the electromagnetic properties of the surrounding environment, etc.\",\n \"In an embodiment, an end of stub coupler 904 can taper towards the wire 702 in order to increase coupling efficiencies.\",\n \"Indeed, the tapering of the end of the stub coupler 904 can provide impedance matching to the wire 702 and reduce reflections, according to an example embodiment of the subject disclosure.\",\n \"For example, an end of the stub coupler 904 can be gradually tapered in order to obtain a desired level of coupling between waves 906 and 908 as illustrated in FIG.\",\n \"9A.\",\n \"In an embodiment, the fastener 910 can be placed such that there is a short length of the stub coupler 904 between the fastener 910 and an end of the stub coupler 904.Maximum coupling efficiencies are realized in this embodiment when the length of the end of the stub coupler 904 that is beyond the fastener 910 is at least several wavelengths long for whatever frequency is being transmitted.\",\n \"Turning now to FIG.\",\n \"9B, a diagram 950 illustrating an example, non-limiting embodiment of an electromagnetic distribution in accordance with various aspects described herein is shown.\",\n \"In particular, an electromagnetic distribution is presented in two dimensions for a transmission device that includes coupler 952, shown in an example stub coupler constructed of a dielectric material.\",\n \"The coupler 952 couples an electromagnetic wave for propagation as a guided wave along an outer surface of a wire 702 or other transmission medium.\",\n \"The coupler 952 guides the electromagnetic wave to a junction at x0 via a symmetrical guided wave mode.\",\n \"While some of the energy of the electromagnetic wave that propagates along the coupler 952 is outside of the coupler 952, the majority of the energy of this electromagnetic wave is contained within the coupler 952.The junction at x0 couples the electromagnetic wave to the wire 702 or other transmission medium at an azimuthal angle corresponding to the bottom of the transmission medium.\",\n \"This coupling induces an electromagnetic wave that is guided to propagate along the outer surface of the wire 702 or other transmission medium via at least one guided wave mode in direction 956.The majority of the energy of the guided electromagnetic wave is outside or, but in close proximity to the outer surface of the wire 702 or other transmission medium.\",\n \"In the example shown, the junction at x0 forms an electromagnetic wave that propagates via both a symmetrical mode and at least one asymmetrical surface mode, such as the first order mode presented in conjunction with FIG.\",\n \"3, that skims the surface of the wire 702 or other transmission medium.\",\n \"It is noted that the graphical representations of guided waves are presented merely to illustrate an example of guided wave coupling and propagation.\",\n \"The actual electric and magnetic fields generated as a result of such wave propagation may vary depending on the frequencies employed, the design and/or configuration of the coupler 952, the dimensions and composition of the wire 702 or other transmission medium, as well as its surface characteristics, its insulation if present, the electromagnetic properties of the surrounding environment, etc.\",\n \"Turning now to FIG.\",\n \"10A, illustrated is a block diagram 1000 of an example, non-limiting embodiment of a coupler and transceiver system in accordance with various aspects described herein.\",\n \"The system is an example of transmission device 101 or 102.In particular, the communication interface 1008 is an example of communications interface 205, the stub coupler 1002 is an example of coupler 220, and the transmitter/receiver device 1006, diplexer 1016, power amplifier 1014, low noise amplifier 1018, frequency mixers 1010 and 1020 and local oscillator 1012 collectively form an example of transceiver 210.In operation, the transmitter/receiver device 1006 launches and receives waves (e.g., guided wave 1004 onto stub coupler 1002).\",\n \"The guided waves 1004 can be used to transport signals received from and sent to a host device, base station, mobile devices, a building or other device by way of a communications interface 1008.The communications interface 1008 can be an integral part of system 1000.Alternatively, the communications interface 1008 can be tethered to system 1000.The communications interface 1008 can comprise a wireless interface for interfacing to the host device, base station, mobile devices, a building or other device utilizing any of various wireless signaling protocols (e.g., LTE, WiFi, WiMAX, IEEE 802.xx, etc.)\",\n \"including an infrared protocol such as an infrared data association (IrDA) protocol or other line of sight optical protocol.\",\n \"The communications interface 1008 can also comprise a wired interface such as a fiber optic line, coaxial cable, twisted pair, category 5 (CAT-5) cable or other suitable wired or optical mediums for communicating with the host device, base station, mobile devices, a building or other device via a protocol such as an Ethernet protocol, universal serial bus (USB) protocol, a data over cable service interface specification (DOCSIS) protocol, a digital subscriber line (DSL) protocol, a Firewire (IEEE 1394) protocol, or other wired or optical protocol.\",\n \"For embodiments where system 1000 functions as a repeater, the communications interface 1008 may not be necessary.\",\n \"The output signals (e.g., Tx) of the communications interface 1008 can be combined with a carrier wave (e.g., millimeter-wave carrier wave) generated by a local oscillator 1012 at frequency mixer 1010.Frequency mixer 1010 can use heterodyning techniques or other frequency shifting techniques to frequency shift the output signals from communications interface 1008.For example, signals sent to and from the communications interface 1008 can be modulated signals such as orthogonal frequency division multiplexed (OFDM) signals formatted in accordance with a Long-Term Evolution (LTE) wireless protocol or other wireless 3G, 4G, 5G or higher voice and data protocol, a Zigbee, WIMAX, UltraWideband or IEEE 802.11 wireless protocol; a wired protocol such as an Ethernet protocol, universal serial bus (USB) protocol, a data over cable service interface specification (DOCSIS) protocol, a digital subscriber line (DSL) protocol, a Firewire (IEEE 1394) protocol or other wired or wireless protocol.\",\n \"In an example embodiment, this frequency conversion can be done in the analog domain, and as a result, the frequency shifting can be done without regard to the type of communications protocol used by a base station, mobile devices, or in-building devices.\",\n \"As new communications technologies are developed, the communications interface 1008 can be upgraded (e.g., updated with software, firmware, and/or hardware) or replaced and the frequency shifting and transmission apparatus can remain, simplifying upgrades.\",\n \"The carrier wave can then be sent to a power amplifier (“PA”) 1014 and can be transmitted via the transmitter receiver device 1006 via the diplexer 1016.Signals received from the transmitter/receiver device 1006 that are directed towards the communications interface 1008 can be separated from other signals via diplexer 1016.The received signal can then be sent to low noise amplifier (“LNA”) 1018 for amplification.\",\n \"A frequency mixer 1020, with help from local oscillator 1012 can downshift the received signal (which is in the millimeter-wave band or around 38 GHz in some embodiments) to the native frequency.\",\n \"The communications interface 1008 can then receive the transmission at an input port (Rx).\",\n \"In an embodiment, transmitter/receiver device 1006 can include a cylindrical or non-cylindrical metal (which, for example, can be hollow in an embodiment, but not necessarily drawn to scale) or other conducting or non-conducting waveguide and an end of the stub coupler 1002 can be placed in or in proximity to the waveguide or the transmitter/receiver device 1006 such that when the transmitter/receiver device 1006 generates a transmission, the guided wave couples to stub coupler 1002 and propagates as a guided wave 1004 about the waveguide surface of the stub coupler 1002.In some embodiments, the guided wave 1004 can propagate in part on the outer surface of the stub coupler 1002 and in part inside the stub coupler 1002.In other embodiments, the guided wave 1004 can propagate substantially or completely on the outer surface of the stub coupler 1002.In yet other embodiments, the guided wave 1004 can propagate substantially or completely inside the stub coupler 1002.In this latter embodiment, the guided wave 1004 can radiate at an end of the stub coupler 1002 (such as the tapered end shown in FIG.\",\n \"4) for coupling to a transmission medium such as a wire 702 of FIG.\",\n \"7.Similarly, if guided wave 1004 is incoming (coupled to the stub coupler 1002 from a wire 702), guided wave 1004 then enters the transmitter/receiver device 1006 and couples to the cylindrical waveguide or conducting waveguide.\",\n \"While transmitter/receiver device 1006 is shown to include a separate waveguide—an antenna, cavity resonator, klystron, magnetron, travelling wave tube, or other radiating element can be employed to induce a guided wave on the coupler 1002, with or without the separate waveguide.\",\n \"In an embodiment, stub coupler 1002 can be wholly constructed of a dielectric material (or another suitable insulating material), without any metallic or otherwise conducting materials therein.\",\n \"Stub coupler 1002 can be composed of nylon, Teflon, polyethylene, a polyamide, other plastics, or other materials that are non-conducting and suitable for facilitating transmission of electromagnetic waves at least in part on an outer surface of such materials.\",\n \"In another embodiment, stub coupler 1002 can include a core that is conducting/metallic, and have an exterior dielectric surface.\",\n \"Similarly, a transmission medium that couples to the stub coupler 1002 for propagating electromagnetic waves induced by the stub coupler 1002 or for supplying electromagnetic waves to the stub coupler 1002 can, in addition to being a bare or insulated wire, be wholly constructed of a dielectric material (or another suitable insulating material), without any metallic or otherwise conducting materials therein.\",\n \"It is noted that although FIG.\",\n \"10A shows that the opening of transmitter receiver device 1006 is much wider than the stub coupler 1002, this is not to scale, and that in other embodiments the width of the stub coupler 1002 is comparable or slightly smaller than the opening of the hollow waveguide.\",\n \"It is also not shown, but in an embodiment, an end of the coupler 1002 that is inserted into the transmitter/receiver device 1006 tapers down in order to reduce reflection and increase coupling efficiencies.\",\n \"Before coupling to the stub coupler 1002, the one or more waveguide modes of the guided wave generated by the transmitter/receiver device 1006 can couple to the stub coupler 1002 to induce one or more wave propagation modes of the guided wave 1004.The wave propagation modes of the guided wave 1004 can be different than the hollow metal waveguide modes due to the different characteristics of the hollow metal waveguide and the dielectric waveguide.\",\n \"For instance, wave propagation modes of the guided wave 1004 can comprise the fundamental transverse electromagnetic mode (Quasi-TEM00), where only small electrical and/or magnetic fields extend in the direction of propagation, and the electric and magnetic fields extend radially outwards from the stub coupler 1002 while the guided waves propagate along the stub coupler 1002.The fundamental transverse electromagnetic mode wave propagation mode may or may not exist inside a waveguide that is hollow.\",\n \"Therefore, the hollow metal waveguide modes that are used by transmitter/receiver device 1006 are waveguide modes that can couple effectively and efficiently to wave propagation modes of stub coupler 1002.It will be appreciated that other constructs or combinations of the transmitter/receiver device 1006 and stub coupler 1002 are possible.\",\n \"For example, a stub coupler 1002′ can be placed tangentially or in parallel (with or without a gap) with respect to an outer surface of the hollow metal waveguide of the transmitter/receiver device 1006′ (corresponding circuitry not shown) as depicted by reference 1000′ of FIG.\",\n \"10B.\",\n \"In another embodiment, not shown by reference 1000′, the stub coupler 1002′ can be placed inside the hollow metal waveguide of the transmitter/receiver device 1006′ without an axis of the stub coupler 1002′ being coaxially aligned with an axis of the hollow metal waveguide of the transmitter/receiver device 1006′.\",\n \"In either of these embodiments, the guided wave generated by the transmitter/receiver device 1006′ can couple to a surface of the stub coupler 1002′ to induce one or more wave propagation modes of the guided wave 1004′ on the stub coupler 1002′ including a fundamental mode (e.g., a symmetric mode) and/or a non-fundamental mode (e.g., asymmetric mode).\",\n \"In one embodiment, the guided wave 1004′ can propagate in part on the outer surface of the stub coupler 1002′ and in part inside the stub coupler 1002′.\",\n \"In another embodiment, the guided wave 1004′ can propagate substantially or completely on the outer surface of the stub coupler 1002′.\",\n \"In yet other embodiments, the guided wave 1004′ can propagate substantially or completely inside the stub coupler 1002′.\",\n \"In this latter embodiment, the guided wave 1004′ can radiate at an end of the stub coupler 1002′ (such as the tapered end shown in FIG.\",\n \"9) for coupling to a transmission medium such as a wire 702 of FIG.\",\n \"9.It will be further appreciated that other constructs the transmitter/receiver device 1006 are possible.\",\n \"For example, a hollow metal waveguide of a transmitter/receiver device 1006″ (corresponding circuitry not shown), depicted in FIG.\",\n \"10B as reference 1000″, can be placed tangentially or in parallel (with or without a gap) with respect to an outer surface of a transmission medium such as the wire 702 of FIG.\",\n \"4 without the use of the stub coupler 1002.In this embodiment, the guided wave generated by the transmitter/receiver device 1006″ can couple to a surface of the wire 702 to induce one or more wave propagation modes of a guided wave 908 on the wire 702 including a fundamental mode (e.g., a symmetric mode) and/or a non-fundamental mode (e.g., asymmetric mode).\",\n \"In another embodiment, the wire 702 can be positioned inside a hollow metal waveguide of a transmitter/receiver device 1006′ (corresponding circuitry not shown) so that an axis of the wire 702 is coaxially (or not coaxially) aligned with an axis of the hollow metal waveguide without the use of the stub coupler 1002—see FIG.\",\n \"10B reference 1000′″.\",\n \"In this embodiment, the guided wave generated by the transmitter/receiver device 1006′″ can couple to a surface of the wire 702 to induce one or more wave propagation modes of a guided wave 908 on the wire including a fundamental mode (e.g., a symmetric mode) and/or a non-fundamental mode (e.g., asymmetric mode).\",\n \"In the embodiments of 1000″ and 1000′″, for a wire 702 having an insulated outer surface, the guided wave 908 can propagate in part on the outer surface of the insulator and in part inside the insulator.\",\n \"In embodiments, the guided wave 908 can propagate substantially or completely on the outer surface of the insulator, or substantially or completely inside the insulator.\",\n \"In the embodiments of 1000″ and 1000′″, for a wire 702 that is a bare conductor, the guided wave 908 can propagate in part on the outer surface of the conductor and in part inside the conductor.\",\n \"In another embodiment, the guided wave 908 can propagate substantially or completely on the outer surface of the conductor.\",\n \"Referring now to FIG.\",\n \"11, a block diagram 1100 illustrating an example, non-limiting embodiment of a dual stub coupler is shown.\",\n \"In particular, a dual coupler design is presented for use in a transmission device, such as transmission device 101 or 102 presented in conjunction with FIG.\",\n \"1.In an embodiment, two or more couplers (such as the stub couplers 1104 and 1106) can be positioned around a wire 1102 in order to receive guided wave 1108.In an embodiment, one coupler is enough to receive the guided wave 1108.In that case, guided wave 1108 couples to coupler 1104 and propagates as guided wave 1110.If the field structure of the guided wave 1108 oscillates or undulates around the wire 1102 due to the particular guided wave mode(s) or various outside factors, then coupler 1106 can be placed such that guided wave 1108 couples to coupler 1106.In some embodiments, four or more couplers can be placed around a portion of the wire 1102, e.g., at 90 degrees or another spacing with respect to each other, in order to receive guided waves that may oscillate or rotate around the wire 1102, that have been induced at different azimuthal orientations or that have non-fundamental or higher order modes that, for example, have lobes and/or nulls or other asymmetries that are orientation dependent.\",\n \"However, it will be appreciated that there may be less than or more than four couplers placed around a portion of the wire 1102 without departing from example embodiments.\",\n \"It should be noted that while couplers 1106 and 1104 are illustrated as stub couplers, any other of the coupler designs described herein including arc couplers, antenna or horn couplers, magnetic couplers, etc., could likewise be used.\",\n \"It will also be appreciated that while some example embodiments have presented a plurality of couplers around at least a portion of a wire 1102, this plurality of couplers can also be considered as part of a single coupler system having multiple coupler subcomponents.\",\n \"For example, two or more couplers can be manufactured as single system that can be installed around a wire in a single installation such that the couplers are either pre-positioned or adjustable relative to each other (either manually or automatically with a controllable mechanism such as a motor or other actuator) in accordance with the single system.\",\n \"Receivers coupled to couplers 1106 and 1104 can use diversity combining to combine signals received from both couplers 1106 and 1104 in order to maximize the signal quality.\",\n \"In other embodiments, if one or the other of the couplers 1104 and 1106 receive a transmission that is above a predetermined threshold, receivers can use selection diversity when deciding which signal to use.\",\n \"Further, while reception by a plurality of couplers 1106 and 1104 is illustrated, transmission by couplers 1106 and 1104 in the same configuration can likewise take place.\",\n \"In particular, a wide range of multi-input multi-output (MIMO) transmission and reception techniques can be employed for transmissions where a transmission device, such as transmission device 101 or 102 presented in conjunction with FIG.\",\n \"1 includes multiple transceivers and multiple couplers.\",\n \"It is noted that the graphical representations of waves 1108 and 1110 are presented merely to illustrate the principles that guided wave 1108 induces or otherwise launches a wave 1110 on a coupler 1104.The actual electric and magnetic fields generated as a result of such wave propagation may vary depending on the frequencies employed, the design of the coupler 1104, the dimensions and composition of the wire 1102, as well as its surface characteristics, its insulation if any, the electromagnetic properties of the surrounding environment, etc.\",\n \"Referring now to FIG.\",\n \"12, a block diagram 1200 illustrating an example, non-limiting embodiment of a repeater system is shown.\",\n \"In particular, a repeater device 1210 is presented for use in a transmission device, such as transmission device 101 or 102 presented in conjunction with FIG.\",\n \"1.In this system, two couplers 1204 and 1214 can be placed near a wire 1202 or other transmission medium such that guided waves 1205 propagating along the wire 1202 are extracted by coupler 1204 as wave 1206 (e.g.\",\n \"as a guided wave), and then are boosted or repeated by repeater device 1210 and launched as a wave 1216 (e.g.\",\n \"as a guided wave) onto coupler 1214.The wave 1216 can then be launched on the wire 1202 and continue to propagate along the wire 1202 as a guided wave 1217.In an embodiment, the repeater device 1210 can receive at least a portion of the power utilized for boosting or repeating through magnetic coupling with the wire 1202, for example, when the wire 1202 is a power line or otherwise contains a power-carrying conductor.\",\n \"It should be noted that while couplers 1204 and 1214 are illustrated as stub couplers, any other of the coupler designs described herein including arc couplers, antenna or horn couplers, magnetic couplers, or the like, could likewise be used.\",\n \"In some embodiments, repeater device 1210 can repeat the transmission associated with wave 1206, and in other embodiments, repeater device 1210 can include a communications interface 205 that extracts data or other signals from the wave 1206 for supplying such data or signals to another network and/or one or more other devices as communication signals 110 or 112 and/or receiving communication signals 110 or 112 from another network and/or one or more other devices and launch guided wave 1216 having embedded therein the received communication signals 110 or 112.In a repeater configuration, receiver waveguide 1208 can receive the wave 1206 from the coupler 1204 and transmitter waveguide 1212 can launch guided wave 1216 onto coupler 1214 as guided wave 1217.Between receiver waveguide 1208 and transmitter waveguide 1212, the signal embedded in guided wave 1206 and/or the guided wave 1216 itself can be amplified to correct for signal loss and other inefficiencies associated with guided wave communications or the signal can be received and processed to extract the data contained therein and regenerated for transmission.\",\n \"In an embodiment, the receiver waveguide 1208 can be configured to extract data from the signal, process the data to correct for data errors utilizing for example error correcting codes, and regenerate an updated signal with the corrected data.\",\n \"The transmitter waveguide 1212 can then transmit guided wave 1216 with the updated signal embedded therein.\",\n \"In an embodiment, a signal embedded in guided wave 1206 can be extracted from the transmission and processed for communication with another network and/or one or more other devices via communications interface 205 as communication signals 110 or 112.Similarly, communication signals 110 or 112 received by the communications interface 205 can be inserted into a transmission of guided wave 1216 that is generated and launched onto coupler 1214 by transmitter waveguide 1212.It is noted that although FIG.\",\n \"12 shows guided wave transmissions 1206 and 1216 entering from the left and exiting to the right respectively, this is merely a simplification and is not intended to be limiting.\",\n \"In other embodiments, receiver waveguide 1208 and transmitter waveguide 1212 can also function as transmitters and receivers respectively, allowing the repeater device 1210 to be bi-directional.\",\n \"In an embodiment, repeater device 1210 can be placed at locations where there are discontinuities or obstacles on the wire 1202 or other transmission medium.\",\n \"In the case where the wire 1202 is a power line, these obstacles can include transformers, connections, utility poles, and other such power line devices.\",\n \"The repeater device 1210 can help the guided (e.g., surface) waves jump over these obstacles on the line and boost the transmission power at the same time.\",\n \"In other embodiments, a coupler can be used to jump over the obstacle without the use of a repeater device.\",\n \"In that embodiment, both ends of the coupler can be tied or fastened to the wire, thus providing a path for the guided wave to travel without being blocked by the obstacle.\",\n \"Turning now to FIG.\",\n \"13, illustrated is a block diagram 1300 of an example, non-limiting embodiment of a bidirectional repeater in accordance with various aspects described herein.\",\n \"In particular, a bidirectional repeater device 1306 is presented for use in a transmission device, such as transmission device 101 or 102 presented in conjunction with FIG.\",\n \"1.It should be noted that while the couplers are illustrated as stub couplers, any other of the coupler designs described herein including arc couplers, antenna or horn couplers, magnetic couplers, or the like, could likewise be used.\",\n \"The bidirectional repeater 1306 can employ diversity paths in the case of when two or more wires or other transmission media are present.\",\n \"Since guided wave transmissions have different transmission efficiencies and coupling efficiencies for transmission medium of different types such as insulated wires, un-insulated wires or other types of transmission media and further, if exposed to the elements, can be affected by weather, and other atmospheric conditions, it can be advantageous to selectively transmit on different transmission media at certain times.\",\n \"In various embodiments, the various transmission media can be designated as a primary, secondary, tertiary, etc.\",\n \"whether or not such designation indicates a preference of one transmission medium over another.\",\n \"In the embodiment shown, the transmission media include an insulated or uninsulated wire 1302 and an insulated or uninsulated wire 1304 (referred to herein as wires 1302 and 1304, respectively).\",\n \"The repeater device 1306 uses a receiver coupler 1308 to receive a guided wave traveling along wire 1302 and repeats the transmission using transmitter waveguide 1310 as a guided wave along wire 1304.In other embodiments, repeater device 1306 can switch from the wire 1304 to the wire 1302, or can repeat the transmissions along the same paths.\",\n \"Repeater device 1306 can include sensors, or be in communication with sensors (or a network management system 1601 depicted in FIG.\",\n \"16A) that indicate conditions that can affect the transmission.\",\n \"Based on the feedback received from the sensors, the repeater device 1306 can make the determination about whether to keep the transmission along the same wire, or transfer the transmission to the other wire.\",\n \"Turning now to FIG.\",\n \"14, illustrated is a block diagram 1400 illustrating an example, non-limiting embodiment of a bidirectional repeater system.\",\n \"In particular, a bidirectional repeater system is presented for use in a transmission device, such as transmission device 101 or 102 presented in conjunction with FIG.\",\n \"1.The bidirectional repeater system includes waveguide coupling devices 1402 and 1404 that receive and transmit transmissions from other coupling devices located in a distributed antenna system or backhaul system.\",\n \"In various embodiments, waveguide coupling device 1402 can receive a transmission from another waveguide coupling device, wherein the transmission has a plurality of subcarriers.\",\n \"Diplexer 1406 can separate the transmission from other transmissions, and direct the transmission to low-noise amplifier (“LNA”) 1408.A frequency mixer 1428, with help from a local oscillator 1412, can downshift the transmission (which is in the millimeter-wave band or around 38 GHz in some embodiments) to a lower frequency, such as a cellular band (˜1.9 GHz) for a distributed antenna system, a native frequency, or other frequency for a backhaul system.\",\n \"An extractor (or demultiplexer) 1432 can extract the signal on a subcarrier and direct the signal to an output component 1422 for optional amplification, buffering or isolation by power amplifier 1424 for coupling to communications interface 205.The communications interface 205 can further process the signals received from the power amplifier 1424 or otherwise transmit such signals over a wireless or wired interface to other devices such as a base station, mobile devices, a building, etc.\",\n \"For the signals that are not being extracted at this location, extractor 1432 can redirect them to another frequency mixer 1436, where the signals are used to modulate a carrier wave generated by local oscillator 1414.The carrier wave, with its subcarriers, is directed to a power amplifier (“PA”) 1416 and is retransmitted by waveguide coupling device 1404 to another system, via diplexer 1420.An LNA 1426 can be used to amplify, buffer or isolate signals that are received by the communication interface 205 and then send the signal to a multiplexer 1434 which merges the signal with signals that have been received from waveguide coupling device 1404.The signals received from coupling device 1404 have been split by diplexer 1420, and then passed through LNA 1418, and downshifted in frequency by frequency mixer 1438.When the signals are combined by multiplexer 1434, they are upshifted in frequency by frequency mixer 1430, and then boosted by PA 1410, and transmitted to another system by waveguide coupling device 1402.In an embodiment bidirectional repeater system can be merely a repeater without the output device 1422.In this embodiment, the multiplexer 1434 would not be utilized and signals from LNA 1418 would be directed to mixer 1430 as previously described.\",\n \"It will be appreciated that in some embodiments, the bidirectional repeater system could also be implemented using two distinct and separate unidirectional repeaters.\",\n \"In an alternative embodiment, a bidirectional repeater system could also be a booster or otherwise perform retransmissions without downshifting and upshifting.\",\n \"Indeed in example embodiment, the retransmissions can be based upon receiving a signal or guided wave and performing some signal or guided wave processing or reshaping, filtering, and/or amplification, prior to retransmission of the signal or guided wave.\",\n \"Referring now to FIG.\",\n \"15, a block diagram 1500 illustrating an example, non-limiting embodiment of a guided wave communications system is shown.\",\n \"This diagram depicts an exemplary environment in which a guided wave communication system, such as the guided wave communication system presented in conjunction with FIG.\",\n \"1, can be used.\",\n \"To provide network connectivity to additional base station devices, a backhaul network that links the communication cells (e.g., macrocells and macrocells) to network devices of a core network correspondingly expands.\",\n \"Similarly, to provide network connectivity to a distributed antenna system, an extended communication system that links base station devices and their distributed antennas is desirable.\",\n \"A guided wave communication system 1500 such as shown in FIG.\",\n \"15 can be provided to enable alternative, increased or additional network connectivity and a waveguide coupling system can be provided to transmit and/or receive guided wave (e.g., surface wave) communications on a transmission medium such as a wire that operates as a single-wire transmission line (e.g., a utility line), and that can be used as a waveguide and/or that otherwise operates to guide the transmission of an electromagnetic wave.\",\n \"The guided wave communication system 1500 can comprise a first instance of a distribution system 1550 that includes one or more base station devices (e.g., base station device 1504) that are communicably coupled to a central office 1501 and/or a macrocell site 1502.Base station device 1504 can be connected by a wired (e.g., fiber and/or cable), or by a wireless (e.g., microwave wireless) connection to the macrocell site 1502 and the central office 1501.A second instance of the distribution system 1560 can be used to provide wireless voice and data services to mobile device 1522 and to residential and/or commercial establishments 1542 (herein referred to as establishments 1542).\",\n \"System 1500 can have additional instances of the distribution systems 1550 and 1560 for providing voice and/or data services to mobile devices 1522-1524 and establishments 1542 as shown in FIG.\",\n \"15.Macrocells such as macrocell site 1502 can have dedicated connections to a mobile network and base station device 1504 or can share and/or otherwise use another connection.\",\n \"Central office 1501 can be used to distribute media content and/or provide internet service provider (ISP) services to mobile devices 1522-1524 and establishments 1542.The central office 1501 can receive media content from a constellation of satellites 1530 (one of which is shown in FIG.\",\n \"15) or other sources of content, and distribute such content to mobile devices 1522-1524 and establishments 1542 via the first and second instances of the distribution system 1550 and 1560.The central office 1501 can also be communicatively coupled to the Internet 1503 for providing internet data services to mobile devices 1522-1524 and establishments 1542.Base station device 1504 can be mounted on, or attached to, utility pole 1516.In other embodiments, base station device 1504 can be near transformers and/or other locations situated nearby a power line.\",\n \"Base station device 1504 can facilitate connectivity to a mobile network for mobile devices 1522 and 1524.Antennas 1512 and 1514, mounted on or near utility poles 1518 and 1520, respectively, can receive signals from base station device 1504 and transmit those signals to mobile devices 1522 and 1524 over a much wider area than if the antennas 1512 and 1514 were located at or near base station device 1504.It is noted that FIG.\",\n \"15 displays three utility poles, in each instance of the distribution systems 1550 and 1560, with one base station device, for purposes of simplicity.\",\n \"In other embodiments, utility pole 1516 can have more base station devices, and more utility poles with distributed antennas and/or tethered connections to establishments 1542.A transmission device 1506, such as transmission device 101 or 102 presented in conjunction with FIG.\",\n \"1, can transmit a signal from base station device 1504 to antennas 1512 and 1514 via utility or power line(s) that connect the utility poles 1516, 1518, and 1520.To transmit the signal, radio source and/or transmission device 1506 upconverts the signal (e.g., via frequency mixing) from base station device 1504 or otherwise converts the signal from the base station device 1504 to a microwave band signal and the transmission device 1506 launches a microwave band wave that propagates as a guided wave traveling along the utility line or other wire as described in previous embodiments.\",\n \"At utility pole 1518, another transmission device 1508 receives the guided wave (and optionally can amplify it as needed or desired or operate as a repeater to receive it and regenerate it) and sends it forward as a guided wave on the utility line or other wire.\",\n \"The transmission device 1508 can also extract a signal from the microwave band guided wave and shift it down in frequency or otherwise convert it to its original cellular band frequency (e.g., 1.9 GHz or other defined cellular frequency) or another cellular (or non-cellular) band frequency.\",\n \"An antenna 1512 can wireless transmit the downshifted signal to mobile device 1522.The process can be repeated by transmission device 1510, antenna 1514 and mobile device 1524, as necessary or desirable.\",\n \"Transmissions from mobile devices 1522 and 1524 can also be received by antennas 1512 and 1514 respectively.\",\n \"The transmission devices 1508 and 1510 can upshift or otherwise convert the cellular band signals to microwave band and transmit the signals as guided wave (e.g., surface wave or other electromagnetic wave) transmissions over the power line(s) to base station device 1504.Media content received by the central office 1501 can be supplied to the second instance of the distribution system 1560 via the base station device 1504 for distribution to mobile devices 1522 and establishments 1542.The transmission device 1510 can be tethered to the establishments 1542 by one or more wired connections or a wireless interface.\",\n \"The one or more wired connections may include without limitation, a power line, a coaxial cable, a fiber cable, a twisted pair cable, a guided wave transmission medium or other suitable wired mediums for distribution of media content and/or for providing internet services.\",\n \"In an example embodiment, the wired connections from the transmission device 1510 can be communicatively coupled to one or more very high bit rate digital subscriber line (VDSL) modems located at one or more corresponding service area interfaces (SAIs—not shown) or pedestals, each SAI or pedestal providing services to a portion of the establishments 1542.The VDSL modems can be used to selectively distribute media content and/or provide internet services to gateways (not shown) located in the establishments 1542.The SAIs or pedestals can also be communicatively coupled to the establishments 1542 over a wired medium such as a power line, a coaxial cable, a fiber cable, a twisted pair cable, a guided wave transmission medium or other suitable wired mediums.\",\n \"In other example embodiments, the transmission device 1510 can be communicatively coupled directly to establishments 1542 without intermediate interfaces such as the SAIs or pedestals.\",\n \"In another example embodiment, system 1500 can employ diversity paths, where two or more utility lines or other wires are strung between the utility poles 1516, 1518, and 1520 (e.g., for example, two or more wires between poles 1516 and 1520) and redundant transmissions from base station/macrocell site 1502 are transmitted as guided waves down the surface of the utility lines or other wires.\",\n \"The utility lines or other wires can be either insulated or uninsulated, and depending on the environmental conditions that cause transmission losses, the coupling devices can selectively receive signals from the insulated or uninsulated utility lines or other wires.\",\n \"The selection can be based on measurements of the signal-to-noise ratio of the wires, or based on determined weather/environmental conditions (e.g., moisture detectors, weather forecasts, etc.).\",\n \"The use of diversity paths with system 1500 can enable alternate routing capabilities, load balancing, increased load handling, concurrent bi-directional or synchronous communications, spread spectrum communications, etc.\",\n \"It is noted that the use of the transmission devices 1506, 1508, and 1510 in FIG.\",\n \"15 are by way of example only, and that in other embodiments, other uses are possible.\",\n \"For instance, transmission devices can be used in a backhaul communication system, providing network connectivity to base station devices.\",\n \"Transmission devices 1506, 1508, and 1510 can be used in many circumstances where it is desirable to transmit guided wave communications over a wire, whether insulated or not insulated.\",\n \"Transmission devices 1506, 1508, and 1510 are improvements over other coupling devices due to no contact or limited physical and/or electrical contact with the wires that may carry high voltages.\",\n \"The transmission device can be located away from the wire (e.g., spaced apart from the wire) and/or located on the wire so long as it is not electrically in contact with the wire, as the dielectric acts as an insulator, allowing for cheap, easy, and/or less complex installation.\",\n \"However, as previously noted conducting or non-dielectric couplers can be employed, for example in configurations where the wires correspond to a telephone network, cable television network, broadband data service, fiber optic communications system or other network employing low voltages or having insulated transmission lines.\",\n \"It is further noted, that while base station device 1504 and macrocell site 1502 are illustrated in an embodiment, other network configurations are likewise possible.\",\n \"For example, devices such as access points or other wireless gateways can be employed in a similar fashion to extend the reach of other networks such as a wireless local area network, a wireless personal area network or other wireless network that operates in accordance with a communication protocol such as a 802.11 protocol, WIMAX protocol, UltraWideband protocol, Bluetooth protocol, Zigbee protocol or other wireless protocol.\",\n \"Referring now to FIGS.\",\n \"16A, 16B and 16C, block diagrams illustrating an example, non-limiting embodiment of a system for managing a communication system are shown.\",\n \"Considering FIG.\",\n \"16A, a waveguide system 1602 is presented for use in a guided wave communications system, such as the system presented in conjunction with FIG.\",\n \"15.The waveguide system 1602 can comprise sensors 1604, a power management system 1605, a transmission device 101 or 102 that includes at least one communication interface 205, transceiver 210 and coupler 220.The waveguide system 1602 can be coupled to a power line 1610 for facilitating guided wave communications in accordance with embodiments described in the subject disclosure.\",\n \"In an example embodiment, the transmission device 101 or 102 includes coupler 220 for inducing electromagnetic waves on a surface of the power line 1610 that longitudinally propagate along the surface of the power line 1610 as described in the subject disclosure.\",\n \"The transmission device 101 or 102 can also serve as a repeater for retransmitting electromagnetic waves on the same power line 1610 or for routing electromagnetic waves between power lines 1610 as shown in FIGS.\",\n \"12-13.The transmission device 101 or 102 includes transceiver 210 configured to, for example, up-convert a signal operating at an original frequency range to electromagnetic waves operating at, exhibiting, or associated with a carrier frequency that propagate along a coupler to induce corresponding guided electromagnetic waves that propagate along a surface of the power line 1610.A carrier frequency can be represented by a center frequency having upper and lower cutoff frequencies that define the bandwidth of the electromagnetic waves.\",\n \"The power line 1610 can be a wire (e.g., single stranded or multi-stranded) having a conducting surface or insulated surface.\",\n \"The transceiver 210 can also receive signals from the coupler 220 and down-convert the electromagnetic waves operating at a carrier frequency to signals at their original frequency.\",\n \"Signals received by the communications interface 205 of transmission device 101 or 102 for up-conversion can include without limitation signals supplied by a central office 1611 over a wired or wireless interface of the communications interface 205, a base station 1614 over a wired or wireless interface of the communications interface 205, wireless signals transmitted by mobile devices 1620 to the base station 1614 for delivery over the wired or wireless interface of the communications interface 205, signals supplied by in-building communication devices 1618 over the wired or wireless interface of the communications interface 205, and/or wireless signals supplied to the communications interface 205 by mobile devices 1612 roaming in a wireless communication range of the communications interface 205.In embodiments where the waveguide system 1602 functions as a repeater, such as shown in FIGS.\",\n \"12-13, the communications interface 205 may or may not be included in the waveguide system 1602.The electromagnetic waves propagating along the surface of the power line 1610 can be modulated and formatted to include packets or frames of data that include a data payload and further include networking information (such as header information for identifying one or more destination waveguide systems 1602).\",\n \"The networking information may be provided by the waveguide system 1602 or an originating device such as the central office 1611, the base station 1614, mobile devices 1620, or in-building devices 1618, or a combination thereof.\",\n \"Additionally, the modulated electromagnetic waves can include error correction data for mitigating signal disturbances.\",\n \"The networking information and error correction data can be used by a destination waveguide system 1602 for detecting transmissions directed to it, and for down-converting and processing with error correction data transmissions that include voice and/or data signals directed to recipient communication devices communicatively coupled to the destination waveguide system 1602.Referring now to the sensors 1604 of the waveguide system 1602, the sensors 1604 can comprise one or more of a temperature sensor 1604a, a disturbance detection sensor 1604b, a loss of energy sensor 1604c, a noise sensor 1604d, a vibration sensor 1604e, an environmental (e.g., weather) sensor 1604f, and/or an image sensor 1604g.\",\n \"The temperature sensor 1604a can be used to measure ambient temperature, a temperature of the transmission device 101 or 102, a temperature of the power line 1610, temperature differentials (e.g., compared to a setpoint or baseline, between transmission device 101 or 102 and 1610, etc.\",\n \"), or any combination thereof.\",\n \"In one embodiment, temperature metrics can be collected and reported periodically to a network management system 1601 by way of the base station 1614.The disturbance detection sensor 1604b can perform measurements on the power line 1610 to detect disturbances such as signal reflections, which may indicate a presence of a downstream disturbance that may impede the propagation of electromagnetic waves on the power line 1610.A signal reflection can represent a distortion resulting from, for example, an electromagnetic wave transmitted on the power line 1610 by the transmission device 101 or 102 that reflects in whole or in part back to the transmission device 101 or 102 from a disturbance in the power line 1610 located downstream from the transmission device 101 or 102.Signal reflections can be caused by obstructions on the power line 1610.For example, a tree limb may cause electromagnetic wave reflections when the tree limb is lying on the power line 1610, or is in close proximity to the power line 1610 which may cause a corona discharge.\",\n \"Other obstructions that can cause electromagnetic wave reflections can include without limitation an object that has been entangled on the power line 1610 (e.g., clothing, a shoe wrapped around a power line 1610 with a shoe string, etc.\",\n \"), a corroded build-up on the power line 1610 or an ice build-up.\",\n \"Power grid components may also impede or obstruct with the propagation of electromagnetic waves on the surface of power lines 1610.Illustrations of power grid components that may cause signal reflections include without limitation a transformer and a joint for connecting spliced power lines.\",\n \"A sharp angle on the power line 1610 may also cause electromagnetic wave reflections.\",\n \"The disturbance detection sensor 1604b can comprise a circuit to compare magnitudes of electromagnetic wave reflections to magnitudes of original electromagnetic waves transmitted by the transmission device 101 or 102 to determine how much a downstream disturbance in the power line 1610 attenuates transmissions.\",\n \"The disturbance detection sensor 1604b can further comprise a spectral analyzer circuit for performing spectral analysis on the reflected waves.\",\n \"The spectral data generated by the spectral analyzer circuit can be compared with spectral profiles via pattern recognition, an expert system, curve fitting, matched filtering or other artificial intelligence, classification or comparison technique to identify a type of disturbance based on, for example, the spectral profile that most closely matches the spectral data.\",\n \"The spectral profiles can be stored in a memory of the disturbance detection sensor 1604b or may be remotely accessible by the disturbance detection sensor 1604b.\",\n \"The profiles can comprise spectral data that models different disturbances that may be encountered on power lines 1610 to enable the disturbance detection sensor 1604b to identify disturbances locally.\",\n \"An identification of the disturbance if known can be reported to the network management system 1601 by way of the base station 1614.The disturbance detection sensor 1604b can also utilize the transmission device 101 or 102 to transmit electromagnetic waves as test signals to determine a roundtrip time for an electromagnetic wave reflection.\",\n \"The round trip time measured by the disturbance detection sensor 1604b can be used to calculate a distance traveled by the electromagnetic wave up to a point where the reflection takes place, which enables the disturbance detection sensor 1604b to calculate a distance from the transmission device 101 or 102 to the downstream disturbance on the power line 1610.The distance calculated can be reported to the network management system 1601 by way of the base station 1614.In one embodiment, the location of the waveguide system 1602 on the power line 1610 may be known to the network management system 1601, which the network management system 1601 can use to determine a location of the disturbance on the power line 1610 based on a known topology of the power grid.\",\n \"In another embodiment, the waveguide system 1602 can provide its location to the network management system 1601 to assist in the determination of the location of the disturbance on the power line 1610.The location of the waveguide system 1602 can be obtained by the waveguide system 1602 from a pre-programmed location of the waveguide system 1602 stored in a memory of the waveguide system 1602, or the waveguide system 1602 can determine its location using a GPS receiver (not shown) included in the waveguide system 1602.The power management system 1605 provides energy to the aforementioned components of the waveguide system 1602.The power management system 1605 can receive energy from solar cells, or from a transformer (not shown) coupled to the power line 1610, or by inductive coupling to the power line 1610 or another nearby power line.\",\n \"The power management system 1605 can also include a backup battery and/or a super capacitor or other capacitor circuit for providing the waveguide system 1602 with temporary power.\",\n \"The loss of energy sensor 1604c can be used to detect when the waveguide system 1602 has a loss of power condition and/or the occurrence of some other malfunction.\",\n \"For example, the loss of energy sensor 1604c can detect when there is a loss of power due to defective solar cells, an obstruction on the solar cells that causes them to malfunction, loss of power on the power line 1610, and/or when the backup power system malfunctions due to expiration of a backup battery, or a detectable defect in a super capacitor.\",\n \"When a malfunction and/or loss of power occurs, the loss of energy sensor 1604c can notify the network management system 1601 by way of the base station 1614.The noise sensor 1604d can be used to measure noise on the power line 1610 that may adversely affect transmission of electromagnetic waves on the power line 1610.The noise sensor 1604d can sense unexpected electromagnetic interference, noise bursts, or other sources of disturbances that may interrupt reception of modulated electromagnetic waves on a surface of a power line 1610.A noise burst can be caused by, for example, a corona discharge, or other source of noise.\",\n \"The noise sensor 1604d can compare the measured noise to a noise profile obtained by the waveguide system 1602 from an internal database of noise profiles or from a remotely located database that stores noise profiles via pattern recognition, an expert system, curve fitting, matched filtering or other artificial intelligence, classification or comparison technique.\",\n \"From the comparison, the noise sensor 1604d may identify a noise source (e.g., corona discharge or otherwise) based on, for example, the noise profile that provides the closest match to the measured noise.\",\n \"The noise sensor 1604d can also detect how noise affects transmissions by measuring transmission metrics such as bit error rate, packet loss rate, jitter, packet retransmission requests, etc.\",\n \"The noise sensor 1604d can report to the network management system 1601 by way of the base station 1614 the identity of noise sources, their time of occurrence, and transmission metrics, among other things.\",\n \"The vibration sensor 1604e can include accelerometers and/or gyroscopes to detect 2D or 3D vibrations on the power line 1610.The vibrations can be compared to vibration profiles that can be stored locally in the waveguide system 1602, or obtained by the waveguide system 1602 from a remote database via pattern recognition, an expert system, curve fitting, matched filtering or other artificial intelligence, classification or comparison technique.\",\n \"Vibration profiles can be used, for example, to distinguish fallen trees from wind gusts based on, for example, the vibration profile that provides the closest match to the measured vibrations.\",\n \"The results of this analysis can be reported by the vibration sensor 1604e to the network management system 1601 by way of the base station 1614.The environmental sensor 1604f can include a barometer for measuring atmospheric pressure, ambient temperature (which can be provided by the temperature sensor 1604a), wind speed, humidity, wind direction, and rainfall, among other things.\",\n \"The environmental sensor 1604f can collect raw information and process this information by comparing it to environmental profiles that can be obtained from a memory of the waveguide system 1602 or a remote database to predict weather conditions before they arise via pattern recognition, an expert system, knowledge-based system or other artificial intelligence, classification or other weather modeling and prediction technique.\",\n \"The environmental sensor 1604f can report raw data as well as its analysis to the network management system 1601.The image sensor 1604g can be a digital camera (e.g., a charged coupled device or CCD imager, infrared camera, etc.)\",\n \"for capturing images in a vicinity of the waveguide system 1602.The image sensor 1604g can include an electromechanical mechanism to control movement (e.g., actual position or focal points/zooms) of the camera for inspecting the power line 1610 from multiple perspectives (e.g., top surface, bottom surface, left surface, right surface and so on).\",\n \"Alternatively, the image sensor 1604g can be designed such that no electromechanical mechanism is needed in order to obtain the multiple perspectives.\",\n \"The collection and retrieval of imaging data generated by the image sensor 1604g can be controlled by the network management system 1601, or can be autonomously collected and reported by the image sensor 1604g to the network management system 1601.Other sensors that may be suitable for collecting telemetry information associated with the waveguide system 1602 and/or the power lines 1610 for purposes of detecting, predicting and/or mitigating disturbances that can impede the propagation of electromagnetic wave transmissions on power lines 1610 (or any other form of a transmission medium of electromagnetic waves) may be utilized by the waveguide system 1602.To mitigate harsh winter conditions, the waveguide system 1602 of FIG.\",\n \"16A can be adapted to use a heater system 1630 such as depicted in FIG.\",\n \"16B.\",\n \"The heater system 1630 can comprise a toroidal inductor 1631 that surrounds a cross-sectional view of a transmission medium 1633, such as the power line 1610 shown in FIG.\",\n \"16A.\",\n \"The toroidal inductor 1631 can be constructed of multiple turns of wire 1636 wrapped around an annular toroid of powdered iron or other ferrite (referred to herein, for illustration purposes, as a ferrite core 1637).\",\n \"In an embodiment where the transmission medium 1633 is a bare wire, a dielectric washer or other insulator 1635 can provide electrical insulation while supporting the wire within the toroidal inductor 1631.Such a dielectric washer can be constructed of Teflon, polystyrene, polyethylene or other dielectric or insulating material.\",\n \"In cases where the transmission medium 1633 is nonconductive or includes an insulating sheath or jacket, the dielectric washer can be eliminated.\",\n \"A power signal conducted by the transmission medium 1633 (e.g., 60 Hz or 50 Hz medium voltage power signal) can induce currents in the wire 1636 wrapped around the ferrite core 1637.The current induced in the wire 1636 can feed a heating element (e.g., a resistor) 1632.To control activation of the heating element 1632, the heating element 1632 can include a controllable switch (not shown) that can be opened to break the circuit formed by the wire 1636 and the heating element 1632, and thereby disable the heating element 1632.When the switch is closed and current begins to flow in the circuit, the heating element 1632 is enabled and thereby emits heat.\",\n \"In one embodiment, the waveguide system 1602 of FIG.\",\n \"16A can utilize the temperature sensor 1604a to measure an internal temperature of the waveguide system 1602 and/or an ambient temperature in a vicinity of the waveguide system 1602.In an embodiment, the waveguide system 1602 can use the image sensor 1604g singly or in combination with the temperature sensor 1604a.\",\n \"The image sensor 1604g can be used to determine if ice and/or snow is accumulating on an outer surface of the waveguide system 1602.To place the toroidal inductor 1631 on a transmission medium 1633, such as a power line, the toroidal inductor 1631 can be inserted into the transmission medium 1633 through a middle cavity opening of the toroidal inductor 1631 if the power line has an open endpoint, or can be separated mechanically at the dashed lines 1639.In the latter embodiment, the toroidal inductor 1631 can be separated to enable placement on the transmission medium 1633 and reattached with a hinge, latch or other mechanical features during an installation process of the waveguide system 1602 on the power line.\",\n \"Turning now to FIG.\",\n \"16D, flow diagram of an example, non-limiting embodiment of a method 1670 in accordance with various aspects described herein is shown.\",\n \"Method 1670 can begin with step 1672 where the waveguide system 1602 monitors the environment using the temperature sensor 1604a and/or the image sensor 1604g as described above.\",\n \"It the waveguide system 1602 determines at step 1674 that the measured temperature (internal and/or ambient) falls below one or more thresholds (e.g., 32° F.) and/or images indicate there is an accumulation of ice and/or snow on a housing assembly of the waveguide system 1602, a circuit 1634 shown in FIG.\",\n \"16B can generate at step 1676 a signal that causes the switch used by the heating element 1632 to close and thereby cause current to flow through the heating element 1632 to emit heat inside the waveguide system 1602.The circuit 1634 can be a controller (e.g., a microprocessor) of the waveguide system 1602.The heat emitted inside the housing assembly of the waveguide system 1602 can be used to prevent malfunction of circuits used by the waveguide system 1602 due to severe weather conditions.\",\n \"Additionally, the heat emitted by the heating element 1632 may radiate sufficiently to heat the housing assembly of the waveguide system 1602 and thereby cause snow or ice to melt.\",\n \"Once the waveguide system 1602 detects at steps 1672 that the temperature and/or snow or ice accumulation has dissipated, the waveguide system 1602 can proceed to step 1678 to disable the heating element 1632 by the circuit 1634 emitting a signal that causes the switch to open and break the circuit to prevent current flow in the heating element 1632.To maintain a steady temperature that prevents ice and/or snow accumulation, the steps of method 1670 can be adapted to operate as a thermostat that maintains a near constant temperature of the waveguide system 1602 to preemptively prevent snow and/or ice accumulation on the housing assembly of the waveguide system 1602.While for purposes of simplicity of explanation, the respective processes are shown and described as a series of blocks in FIG.\",\n \"16D, it is to be understood and appreciated that the claimed subject matter is not limited by the order of the blocks, as some blocks may occur in different orders and/or concurrently with other blocks from what is depicted and described herein.\",\n \"Moreover, not all illustrated blocks may be required to implement the methods described herein.\",\n \"Referring now to FIG.\",\n \"16C, block diagram 1650 illustrates an example, non-limiting embodiment of a system for managing a power grid 1653 and a communication system 1655 embedded therein or associated therewith in accordance with various aspects described herein.\",\n \"The communication system 1655 comprises a plurality of waveguide systems 1602 coupled to power lines 1610 of the power grid 1653.At least a portion of the waveguide systems 1602 used in the communication system 1655 can be in direct communication with a base station 1614 and/or the network management system 1601.Waveguide systems 1602 not directly connected to a base station 1614 or the network management system 1601 can engage in communication sessions with either a base station 1614 or the network management system 1601 by way of other downstream waveguide systems 1602 connected to a base station 1614 or the network management system 1601.The network management system 1601 can be communicatively coupled to equipment of a utility company 1652 and equipment of a communications service provider 1654 for providing each entity, status information associated with the power grid 1653 and the communication system 1655, respectively.\",\n \"The network management system 1601, the equipment of the utility company 1652, and the communications service provider 1654 can access communication devices utilized by utility company personnel 1656 and/or communication devices utilized by communications service provider personnel 1658 for purposes of providing status information and/or for directing such personnel in the management of the power grid 1653 and/or communication system 1655.FIG.\",\n \"17A illustrates a flow diagram of an example, non-limiting embodiment of a method 1700 for detecting and mitigating disturbances occurring in a communication network of the systems of FIGS.\",\n \"16A-16C.\",\n \"Method 1700 can begin with step 1702 where a waveguide system 1602 transmits and receives messages embedded in, or forming part of, modulated electromagnetic waves or another type of electromagnetic waves traveling along a surface of a power line 1610.The messages can be voice messages, streaming video, and/or other data/information exchanged between communication devices communicatively coupled to the communication system 1655.At step 1704 the sensors 1604 of the waveguide system 1602 can collect sensing data.\",\n \"In an embodiment, the sensing data can be collected in step 1704 prior to, during, or after the transmission and/or receipt of messages in step 1702.At step 1706 the waveguide system 1602 (or the sensors 1604 themselves) can determine from the sensing data an actual or predicted occurrence of a disturbance in the communication system 1655 that can affect communications originating from (e.g., transmitted by) or received by the waveguide system 1602.The waveguide system 1602 (or the sensors 1604) can process temperature data, signal reflection data, loss of energy data, noise data, vibration data, environmental data, or any combination thereof to make this determination.\",\n \"The waveguide system 1602 (or the sensors 1604) may also detect, identify, estimate, or predict the source of the disturbance and/or its location in the communication system 1655.If a disturbance is neither detected/identified nor predicted/estimated at step 1708, the waveguide system 1602 can proceed to step 1702 where it continues to transmit and receive messages embedded in, or forming part of, modulated electromagnetic waves traveling along a surface of the power line 1610.If at step 1708 a disturbance is detected/identified or predicted/estimated to occur, the waveguide system 1602 proceeds to step 1710 to determine if the disturbance adversely affects (or alternatively, is likely to adversely affect or the extent to which it may adversely affect) transmission or reception of messages in the communication system 1655.In one embodiment, a duration threshold and a frequency of occurrence threshold can be used at step 1710 to determine when a disturbance adversely affects communications in the communication system 1655.For illustration purposes only, assume a duration threshold is set to 500 ms, while a frequency of occurrence threshold is set to 5 disturbances occurring in an observation period of 10 sec.\",\n \"Thus, a disturbance having a duration greater than 500 ms will trigger the duration threshold.\",\n \"Additionally, any disturbance occurring more than 5 times in a 10 sec time interval will trigger the frequency of occurrence threshold.\",\n \"In one embodiment, a disturbance may be considered to adversely affect signal integrity in the communication systems 1655 when the duration threshold alone is exceeded.\",\n \"In another embodiment, a disturbance may be considered as adversely affecting signal integrity in the communication systems 1655 when both the duration threshold and the frequency of occurrence threshold are exceeded.\",\n \"The latter embodiment is thus more conservative than the former embodiment for classifying disturbances that adversely affect signal integrity in the communication system 1655.It will be appreciated that many other algorithms and associated parameters and thresholds can be utilized for step 1710 in accordance with example embodiments.\",\n \"Referring back to method 1700, if at step 1710 the disturbance detected at step 1708 does not meet the condition for adversely affected communications (e.g., neither exceeds the duration threshold nor the frequency of occurrence threshold), the waveguide system 1602 may proceed to step 1702 and continue processing messages.\",\n \"For instance, if the disturbance detected in step 1708 has a duration of 1 msec with a single occurrence in a 10 sec time period, then neither threshold will be exceeded.\",\n \"Consequently, such a disturbance may be considered as having a nominal effect on signal integrity in the communication system 1655 and thus would not be flagged as a disturbance requiring mitigation.\",\n \"Although not flagged, the occurrence of the disturbance, its time of occurrence, its frequency of occurrence, spectral data, and/or other useful information, may be reported to the network management system 1601 as telemetry data for monitoring purposes.\",\n \"Referring back to step 1710, if on the other hand the disturbance satisfies the condition for adversely affected communications (e.g., exceeds either or both thresholds), the waveguide system 1602 can proceed to step 1712 and report the incident to the network management system 1601.The report can include raw sensing data collected by the sensors 1604, a description of the disturbance if known by the waveguide system 1602, a time of occurrence of the disturbance, a frequency of occurrence of the disturbance, a location associated with the disturbance, parameters readings such as bit error rate, packet loss rate, retransmission requests, jitter, latency and so on.\",\n \"If the disturbance is based on a prediction by one or more sensors of the waveguide system 1602, the report can include a type of disturbance expected, and if predictable, an expected time occurrence of the disturbance, and an expected frequency of occurrence of the predicted disturbance when the prediction is based on historical sensing data collected by the sensors 1604 of the waveguide system 1602.At step 1714, the network management system 1601 can determine a mitigation, circumvention, or correction technique, which may include directing the waveguide system 1602 to reroute traffic to circumvent the disturbance if the location of the disturbance can be determined.\",\n \"In one embodiment, the waveguide coupling device 1402 detecting the disturbance may direct a repeater such as the one shown in FIGS.\",\n \"13-14 to connect the waveguide system 1602 from a primary power line affected by the disturbance to a secondary power line to enable the waveguide system 1602 to reroute traffic to a different transmission medium and avoid the disturbance.\",\n \"In an embodiment where the waveguide system 1602 is configured as a repeater the waveguide system 1602 can itself perform the rerouting of traffic from the primary power line to the secondary power line.\",\n \"It is further noted that for bidirectional communications (e.g., full or half-duplex communications), the repeater can be configured to reroute traffic from the secondary power line back to the primary power line for processing by the waveguide system 1602.In another embodiment, the waveguide system 1602 can redirect traffic by instructing a first repeater situated upstream of the disturbance and a second repeater situated downstream of the disturbance to redirect traffic from a primary power line temporarily to a secondary power line and back to the primary power line in a manner that avoids the disturbance.\",\n \"It is further noted that for bidirectional communications (e.g., full or half-duplex communications), repeaters can be configured to reroute traffic from the secondary power line back to the primary power line.\",\n \"To avoid interrupting existing communication sessions occurring on a secondary power line, the network management system 1601 may direct the waveguide system 1602 to instruct repeater(s) to utilize unused time slot(s) and/or frequency band(s) of the secondary power line for redirecting data and/or voice traffic away from the primary power line to circumvent the disturbance.\",\n \"At step 1716, while traffic is being rerouted to avoid the disturbance, the network management system 1601 can notify equipment of the utility company 1652 and/or equipment of the communications service provider 1654, which in turn may notify personnel of the utility company 1656 and/or personnel of the communications service provider 1658 of the detected disturbance and its location if known.\",\n \"Field personnel from either party can attend to resolving the disturbance at a determined location of the disturbance.\",\n \"Once the disturbance is removed or otherwise mitigated by personnel of the utility company and/or personnel of the communications service provider, such personnel can notify their respective companies and/or the network management system 1601 utilizing field equipment (e.g., a laptop computer, smartphone, etc.)\",\n \"communicatively coupled to network management system 1601, and/or equipment of the utility company and/or the communications service provider.\",\n \"The notification can include a description of how the disturbance was mitigated and any changes to the power lines 1610 that may change a topology of the communication system 1655.Once the disturbance has been resolved (as determined in decision 1718), the network management system 1601 can direct the waveguide system 1602 at step 1720 to restore the previous routing configuration used by the waveguide system 1602 or route traffic according to a new routing configuration if the restoration strategy used to mitigate the disturbance resulted in a new network topology of the communication system 1655.In another embodiment, the waveguide system 1602 can be configured to monitor mitigation of the disturbance by transmitting test signals on the power line 1610 to determine when the disturbance has been removed.\",\n \"Once the waveguide system 1602 detects an absence of the disturbance it can autonomously restore its routing configuration without assistance by the network management system 1601 if it determines the network topology of the communication system 1655 has not changed, or it can utilize a new routing configuration that adapts to a detected new network topology.\",\n \"FIG.\",\n \"17B illustrates a flow diagram of an example, non-limiting embodiment of a method 1750 for detecting and mitigating disturbances occurring in a communication network of the system of FIGS.\",\n \"16A-16C.\",\n \"In one embodiment, method 1750 can begin with step 1752 where a network management system 1601 receives from equipment of the utility company 1652 or equipment of the communications service provider 1654 maintenance information associated with a maintenance schedule.\",\n \"The network management system 1601 can at step 1754 identify from the maintenance information, maintenance activities to be performed during the maintenance schedule.\",\n \"From these activities, the network management system 1601 can detect a disturbance resulting from the maintenance (e.g., scheduled replacement of a power line 1610, scheduled replacement of a waveguide system 1602 on the power line 1610, scheduled reconfiguration of power lines 1610 in the power grid 1653, etc.).\",\n \"In another embodiment, the network management system 1601 can receive at step 1755 telemetry information from one or more waveguide systems 1602.The telemetry information can include among other things an identity of each waveguide system 1602 submitting the telemetry information, measurements taken by sensors 1604 of each waveguide system 1602, information relating to predicted, estimated, or actual disturbances detected by the sensors 1604 of each waveguide system 1602, location information associated with each waveguide system 1602, an estimated location of a detected disturbance, an identification of the disturbance, and so on.\",\n \"The network management system 1601 can determine from the telemetry information a type of disturbance that may be adverse to operations of the waveguide, transmission of the electromagnetic waves along the wire surface, or both.\",\n \"The network management system 1601 can also use telemetry information from multiple waveguide systems 1602 to isolate and identify the disturbance.\",\n \"Additionally, the network management system 1601 can request telemetry information from waveguide systems 1602 in a vicinity of an affected waveguide system 1602 to triangulate a location of the disturbance and/or validate an identification of the disturbance by receiving similar telemetry information from other waveguide systems 1602.In yet another embodiment, the network management system 1601 can receive at step 1756 an unscheduled activity report from maintenance field personnel.\",\n \"Unscheduled maintenance may occur as result of field calls that are unplanned or as a result of unexpected field issues discovered during field calls or scheduled maintenance activities.\",\n \"The activity report can identify changes to a topology configuration of the power grid 1653 resulting from field personnel addressing discovered issues in the communication system 1655 and/or power grid 1653, changes to one or more waveguide systems 1602 (such as replacement or repair thereof), mitigation of disturbances performed if any, and so on.\",\n \"At step 1758, the network management system 1601 can determine from reports received according to steps 1752 through 1756 if a disturbance will occur based on a maintenance schedule, or if a disturbance has occurred or is predicted to occur based on telemetry data, or if a disturbance has occurred due to an unplanned maintenance identified in a field activity report.\",\n \"From any of these reports, the network management system 1601 can determine whether a detected or predicted disturbance requires rerouting of traffic by the affected waveguide systems 1602 or other waveguide systems 1602 of the communication system 1655.When a disturbance is detected or predicted at step 1758, the network management system 1601 can proceed to step 1760 where it can direct one or more waveguide systems 1602 to reroute traffic to circumvent the disturbance.\",\n \"When the disturbance is permanent due to a permanent topology change of the power grid 1653, the network management system 1601 can proceed to step 1770 and skip steps 1762, 1764, 1766, and 1772.At step 1770, the network management system 1601 can direct one or more waveguide systems 1602 to use a new routing configuration that adapts to the new topology.\",\n \"However, when the disturbance has been detected from telemetry information supplied by one or more waveguide systems 1602, the network management system 1601 can notify maintenance personnel of the utility company 1656 or the communications service provider 1658 of a location of the disturbance, a type of disturbance if known, and related information that may be helpful to such personnel to mitigate the disturbance.\",\n \"When a disturbance is expected due to maintenance activities, the network management system 1601 can direct one or more waveguide systems 1602 to reconfigure traffic routes at a given schedule (consistent with the maintenance schedule) to avoid disturbances caused by the maintenance activities during the maintenance schedule.\",\n \"Returning back to step 1760 and upon its completion, the process can continue with step 1762.At step 1762, the network management system 1601 can monitor when the disturbance(s) have been mitigated by field personnel.\",\n \"Mitigation of a disturbance can be detected at step 1762 by analyzing field reports submitted to the network management system 1601 by field personnel over a communications network (e.g., cellular communication system) utilizing field equipment (e.g., a laptop computer or handheld computer/device).\",\n \"If field personnel have reported that a disturbance has been mitigated, the network management system 1601 can proceed to step 1764 to determine from the field report whether a topology change was required to mitigate the disturbance.\",\n \"A topology change can include rerouting a power line 1610, reconfiguring a waveguide system 1602 to utilize a different power line 1610, otherwise utilizing an alternative link to bypass the disturbance and so on.\",\n \"If a topology change has taken place, the network management system 1601 can direct at step 1770 one or more waveguide systems 1602 to use a new routing configuration that adapts to the new topology.\",\n \"If, however, a topology change has not been reported by field personnel, the network management system 1601 can proceed to step 1766 where it can direct one or more waveguide systems 1602 to send test signals to test a routing configuration that had been used prior to the detected disturbance(s).\",\n \"Test signals can be sent to affected waveguide systems 1602 in a vicinity of the disturbance.\",\n \"The test signals can be used to determine if signal disturbances (e.g., electromagnetic wave reflections) are detected by any of the waveguide systems 1602.If the test signals confirm that a prior routing configuration is no longer subject to previously detected disturbance(s), then the network management system 1601 can at step 1772 direct the affected waveguide systems 1602 to restore a previous routing configuration.\",\n \"If, however, test signals analyzed by one or more waveguide coupling device 1402 and reported to the network management system 1601 indicate that the disturbance(s) or new disturbance(s) are present, then the network management system 1601 will proceed to step 1768 and report this information to field personnel to further address field issues.\",\n \"The network management system 1601 can in this situation continue to monitor mitigation of the disturbance(s) at step 1762.In the aforementioned embodiments, the waveguide systems 1602 can be configured to be self-adapting to changes in the power grid 1653 and/or to mitigation of disturbances.\",\n \"That is, one or more affected waveguide systems 1602 can be configured to self-monitor mitigation of disturbances and reconfigure traffic routes without requiring instructions to be sent to them by the network management system 1601.In this embodiment, the one or more waveguide systems 1602 that are self-configurable can inform the network management system 1601 of its routing choices so that the network management system 1601 can maintain a macro-level view of the communication topology of the communication system 1655.While for purposes of simplicity of explanation, the respective processes are shown and described as a series of blocks in FIGS.\",\n \"17A and 17B, respectively, it is to be understood and appreciated that the claimed subject matter is not limited by the order of the blocks, as some blocks may occur in different orders and/or concurrently with other blocks from what is depicted and described herein.\",\n \"Moreover, not all illustrated blocks may be required to implement the methods described herein.\",\n \"Turning now to FIG.\",\n \"18, a block diagram illustrating an example, non-limiting embodiment of a cross-sectional view of transmission media 1800 in accordance with various aspects described herein is shown.\",\n \"In one embodiment, transmission media 1800 can comprise a bundle of power lines sharing a common cable.\",\n \"FIG.\",\n \"18 depicts a first power line 1804, a second power line 1806, and a third power line 1808 sharing a common cable 1802 that may itself be either another power line or a support cable used to support the bundle.\",\n \"Other configurations of more or fewer power lines can be used in accordance with the embodiments of the subject disclosure.\",\n \"The power lines 1804, 1806 and 1808 and common cable 1802 can be coupled to multiple spacers such as the spacer 1900 depicted in FIG.\",\n \"19.Each spacer 1900 can have clamps 1902 which can be used to support the power lines 1804, 1806 and 1808 and the common cable 1802.For power lines held by utility poles over long distances, the spacers 1900 can be separated longitudinally from each other such as to achieve a uniform spacing between the power lines 1804, 1806 and 1808 and the common cable 1802.The power lines 1804, 1806 and 1808 can be constructed with insulated or uninsulated conductors.\",\n \"Similarly, the common cable 1802 can be an insulated or uninsulated conductor.\",\n \"In various embodiments, the bundle of power lines 1804, 1806 and 1808 share the common cable 1802 in order to support multiple electromagnetic communication paths.\",\n \"For example, the separation between the common cable 1802 and the first power line 1804 can form a first twin-lead cable, which can be used for propagating a first electromagnetic wave 1804′ that propagates longitudinally along the first power line 1804 and the common cable 1802 and at least a portion of the area in between (i.e., in a longitudinal direction that points in and/or out of the page).\",\n \"Similarly, the separation between the common cable 1802 and the second power line 1806 can form a second twin-lead cable, which can be used for propagating a second electromagnetic wave 1806′ that propagates longitudinally along the second power line 1806 and the common cable 1802 and at least a portion of the area in between.\",\n \"Lastly, the separation between the common cable 1802 and the third power line 1808 can form a third twin-lead cable, which can be used for propagating a third electromagnetic wave 1808′ that propagates longitudinally along the third power line 1806 and the common cable 1802 and at least a portion of the area in between.\",\n \"Each twin-lead pair can serve as a transmission line for propagation of guided electromagnetic waves.\",\n \"From the illustration of FIG.\",\n \"18, a relationship exists between the number of cables and the number of twin-leads that can be used.\",\n \"Particularly, N−1 twin-leads can be formed from a bundle of cables, where N is a sum of a total number of power lines and the common cable.\",\n \"Based on FIG.\",\n \"18, three twin-lead cables (four total cables−one) are possible.\",\n \"Each twin-lead cable can have an impedance range (e.g., from 600 ohms to 75 ohms) that determines an operating frequency range of electromagnetic waves that can be guided by each twin-lead cable (e.g., 3 KHz to 300 GHz).\",\n \"The embodiments of FIGS.\",\n \"18-19 can also be combined with the embodiments described earlier for transporting electromagnetic waves on a single transmission medium.\",\n \"For example, a waveguide system 1602 such as described earlier in FIG.\",\n \"16A can be configured to exchange electromagnetic waves with other waveguide systems 1602 over the first power line 1804, while at the same time another system exchanges electromagnetic waves guided by the twin-lead comprising the first power line 1804 and the common cable 1802.Guided electromagnetic waves can also be transmitted individually on the second power line 1806, the third power line 1808 and the common cable 1802.Accordingly, the configuration of FIG.\",\n \"18, can be used as seven communication pathways: A) three communication pathways via the three twin-lead cables, and B) four communication pathways via the four cables used for exchanging electromagnetic waves traveling on an outer surface of each cable.\",\n \"Turning now to FIG.\",\n \"20, a flow diagram of an example, non-limiting embodiment of a method 2000 that can be used for exchanging electromagnetic waves with transmission lines depicted in FIG.\",\n \"18 in accordance with various aspects described herein is shown.\",\n \"Method 2002 can begin with a plurality of launchers receiving a plurality of communication signals.\",\n \"Each launcher can be configured to receive a select one of the communication signals.\",\n \"Each communication signal can include data such as voice, streaming content or other forms of communication data generated by different sources.\",\n \"At step 2004, the launchers can be configured to transmit a plurality of electromagnetic waves by way of the bundle of transmission media 1800 such as shown in FIG.\",\n \"18.Each twin-lead of the bundle of transmission media 1800, for example, can be connected to a launcher (not shown) which can launch between the power line and the common cable forming an electromagnetic wave guided by the twin-lead, which can propagate longitudinally to a receiver (not shown) at a downstream location.\",\n \"In one embodiment, the plurality of launchers can be integrated with the spacer 1900 of FIG.\",\n \"19.Each launcher can have a coupler that, for example, makes contact with a corresponding power lines supported by clamp 1902 to excite an electromagnetic wave at a corresponding cable pairs of each twin lead, including the shared cable.\",\n \"The launcher can be a radio frequency (RF) transmitter that includes RF circuits for modulating and transmitting RF signals.\",\n \"Similarly, the receiver can be an RF receiver that includes RF circuits for receiving and demodulating RF signals.\",\n \"At step 2006, downstream receivers, each coupled to a particular twin-lead of the bundle of transmission media 1800, can receive the electromagnetic wave and retrieve at step 2008 a corresponding communication signal.\",\n \"For bi-directional communications, method 2000 can be adapted so that launchers and receivers are combined to form transceivers at each end such as the transmission devices 101 and 102 of FIG.\",\n \"1 for transmitting guided waves 120 and 122, respectively.\",\n \"As noted earlier, the individual cables of the bundled transmission media 1800 can also be used for exchanging electromagnetic waves on an outer surface of each cable.\",\n \"Accordingly, method 2000 can be adapted to use waveguide systems to add more communication pathways if so desired.\",\n \"It is further noted that a dipole antenna can be used as a launcher to excite and/or extract energy from each twin lead transmission line previously described by the illustration of FIG.\",\n \"18.For example, the ends of the dipole antenna can be sized to fit between the conductors of the twin lead (orthogonal to them), can be positioned in a same plane as the spacer 1900 and oriented between the shared cable and corresponding power line in order to send and receive guided wave communication via the corresponding twin lead communication path.\",\n \"In some embodiments, a dipole antenna can be placed where line 1804′ is shown in FIG.\",\n \"18, and can be supplied signals at center feed points of the antenna.\",\n \"In one embodiment, the spacer 1900 can be configured with a dipole antenna painted or otherwise integrated onto or molded inside a plastic material of the spacer 1900.The dimensions of the dipole antenna can dictate an operating frequency of signals supplied to the twin lead.\",\n \"In one embodiment, the electronics of the launcher can be molded into the spacer 1900, and can be configured to draw power from any two conductors held by the spacer 1900.In another embodiment, a millimeter wave or terahertz communication device having a small antenna can be positioned at a center location of the spacer 1900 (e.g., diamond shaped null 1903).\",\n \"The transmitter can be configured to transmit signals that support very high bandwidth communications between spacers 1900 using the open space between the wires supported by the spacers 1900.It will be appreciated that the foregoing embodiments can also be adapted without the use of a spacer 1900.For example, the embodiments of the subject disclosure can be applied to any two parallel suspended conductors as a twin lead transmission line, including those that hang at a top section of a utility pole (without a spacer 1900).\",\n \"To accommodate variable spacing between conductors not supported by spacers 1900, an operating frequency of the electromagnetic waves supplied to the twin leads can be lowered to provide reliable communications.\",\n \"In one embodiment, a (dipole) coupler antenna system a Yagi antenna, or other launcher can be attached to a cross arm at a top section of a utility pole to supply electromagnetic wave signals to pairs of power lines (not supported by spacers 1900) that are being used as a twin lead.\",\n \"Other variants of the subject disclosure are contemplated.\",\n \"While for purposes of simplicity of explanation, the respective processes are shown and described as a series of blocks in FIG.\",\n \"20, it is to be understood and appreciated that the claimed subject matter is not limited by the order of the blocks, as some blocks may occur in different orders and/or concurrently with other blocks from what is depicted and described herein.\",\n \"Moreover, not all illustrated blocks may be required to implement the methods described herein.\",\n \"Referring now to FIG.\",\n \"21, there is illustrated a block diagram of a computing environment in accordance with various aspects described herein.\",\n \"In order to provide additional context for various embodiments of the embodiments described herein, FIG.\",\n \"21 and the following discussion are intended to provide a brief, general description of a suitable computing environment 2100 in which the various embodiments of the subject disclosure can be implemented.\",\n \"While the embodiments have been described above in the general context of computer-executable instructions that can run on one or more computers, those skilled in the art will recognize that the embodiments can be also implemented in combination with other program modules and/or as a combination of hardware and software.\",\n \"Generally, program modules comprise routines, programs, components, data structures, etc., that perform particular tasks or implement particular abstract data types.\",\n \"Moreover, those skilled in the art will appreciate that the inventive methods can be practiced with other computer system configurations, comprising single-processor or multiprocessor computer systems, minicomputers, mainframe computers, as well as personal computers, hand-held computing devices, microprocessor-based or programmable consumer electronics, and the like, each of which can be operatively coupled to one or more associated devices.\",\n \"As used herein, a processing circuit includes processor as well as other application specific circuits such as an application specific integrated circuit, digital logic circuit, state machine, programmable gate array or other circuit that processes input signals or data and that produces output signals or data in response thereto.\",\n \"It should be noted that while any functions and features described herein in association with the operation of a processor could likewise be performed by a processing circuit.\",\n \"The terms “first,” “second,” “third,” and so forth, as used in the claims, unless otherwise clear by context, is for clarity only and doesn't otherwise indicate or imply any order in time.\",\n \"For instance, “a first determination,” “a second determination,” and “a third determination,” does not indicate or imply that the first determination is to be made before the second determination, or vice versa, etc.\",\n \"The illustrated embodiments of the embodiments herein can be also practiced in distributed computing environments where certain tasks are performed by remote processing devices that are linked through a communications network.\",\n \"In a distributed computing environment, program modules can be located in both local and remote memory storage devices.\",\n \"Computing devices typically comprise a variety of media, which can comprise computer-readable storage media and/or communications media, which two terms are used herein differently from one another as follows.\",\n \"Computer-readable storage media can be any available storage media that can be accessed by the computer and comprises both volatile and nonvolatile media, removable and non-removable media.\",\n \"By way of example, and not limitation, computer-readable storage media can be implemented in connection with any method or technology for storage of information such as computer-readable instructions, program modules, structured data or unstructured data.\",\n \"Computer-readable storage media can comprise, but are not limited to, random access memory (RAM), read only memory (ROM), electrically erasable programmable read only memory (EEPROM), flash memory or other memory technology, compact disk read only memory (CD-ROM), digital versatile disk (DVD) or other optical disk storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices or other tangible and/or non-transitory media which can be used to store desired information.\",\n \"In this regard, the terms “tangible” or “non-transitory” herein as applied to storage, memory or computer-readable media, are to be understood to exclude only propagating transitory signals per se as modifiers and do not relinquish rights to all standard storage, memory or computer-readable media that are not only propagating transitory signals per se.\",\n \"Computer-readable storage media can be accessed by one or more local or remote computing devices, e.g., via access requests, queries or other data retrieval protocols, for a variety of operations with respect to the information stored by the medium.\",\n \"Communications media typically embody computer-readable instructions, data structures, program modules or other structured or unstructured data in a data signal such as a modulated data signal, e.g., a carrier wave or other transport mechanism, and comprises any information delivery or transport media.\",\n \"The term “modulated data signal” or signals refers to a signal that has one or more of its characteristics set or changed in such a manner as to encode information in one or more signals.\",\n \"By way of example, and not limitation, communication media comprise wired media, such as a wired network or direct-wired connection, and wireless media such as acoustic, RF, infrared and other wireless media.\",\n \"With reference again to FIG.\",\n \"21, the example environment 2100 for transmitting and receiving signals via or forming at least part of a base station (e.g., base station devices 1504, macrocell site 1502, or base stations 1614) or central office (e.g., central office 1501 or 1611).\",\n \"At least a portion of the example environment 2100 can also be used for transmission devices 101 or 102.The example environment can comprise a computer 2102, the computer 2102 comprising a processing unit 2104, a system memory 2106 and a system bus 2108.The system bus 2108 couples system components including, but not limited to, the system memory 2106 to the processing unit 2104.The processing unit 2104 can be any of various commercially available processors.\",\n \"Dual microprocessors and other multiprocessor architectures can also be employed as the processing unit 2104.The system bus 2108 can be any of several types of bus structure that can further interconnect to a memory bus (with or without a memory controller), a peripheral bus, and a local bus using any of a variety of commercially available bus architectures.\",\n \"The system memory 2106 comprises ROM 2110 and RAM 2112.A basic input/output system (BIOS) can be stored in a non-volatile memory such as ROM, erasable programmable read only memory (EPROM), EEPROM, which BIOS contains the basic routines that help to transfer information between elements within the computer 2102, such as during startup.\",\n \"The RAM 2112 can also comprise a high-speed RAM such as static RAM for caching data.\",\n \"The computer 2102 further comprises an internal hard disk drive (HDD) 2114 (e.g., EIDE, SATA), which internal hard disk drive 2114 can also be configured for external use in a suitable chassis (not shown), a magnetic floppy disk drive (FDD) 2116, (e.g., to read from or write to a removable diskette 2118) and an optical disk drive 2120, (e.g., reading a CD-ROM disk 2122 or, to read from or write to other high capacity optical media such as the DVD).\",\n \"The hard disk drive 2114, magnetic disk drive 2116 and optical disk drive 2120 can be connected to the system bus 2108 by a hard disk drive interface 2124, a magnetic disk drive interface 2126 and an optical drive interface 2128, respectively.\",\n \"The interface 2124 for external drive implementations comprises at least one or both of Universal Serial Bus (USB) and Institute of Electrical and Electronics Engineers (IEEE) 1394 interface technologies.\",\n \"Other external drive connection technologies are within contemplation of the embodiments described herein.\",\n \"The drives and their associated computer-readable storage media provide nonvolatile storage of data, data structures, computer-executable instructions, and so forth.\",\n \"For the computer 2102, the drives and storage media accommodate the storage of any data in a suitable digital format.\",\n \"Although the description of computer-readable storage media above refers to a hard disk drive (HDD), a removable magnetic diskette, and a removable optical media such as a CD or DVD, it should be appreciated by those skilled in the art that other types of storage media which are readable by a computer, such as zip drives, magnetic cassettes, flash memory cards, cartridges, and the like, can also be used in the example operating environment, and further, that any such storage media can contain computer-executable instructions for performing the methods described herein.\",\n \"A number of program modules can be stored in the drives and RAM 2112, comprising an operating system 2130, one or more application programs 2132, other program modules 2134 and program data 2136.All or portions of the operating system, applications, modules, and/or data can also be cached in the RAM 2112.The systems and methods described herein can be implemented utilizing various commercially available operating systems or combinations of operating systems.\",\n \"Examples of application programs 2132 that can be implemented and otherwise executed by processing unit 2104 include the diversity selection determining performed by transmission device 101 or 102.A user can enter commands and information into the computer 2102 through one or more wired/wireless input devices, e.g., a keyboard 2138 and a pointing device, such as a mouse 2140.Other input devices (not shown) can comprise a microphone, an infrared (IR) remote control, a joystick, a game pad, a stylus pen, touch screen or the like.\",\n \"These and other input devices are often connected to the processing unit 2104 through an input device interface 2142 that can be coupled to the system bus 2108, but can be connected by other interfaces, such as a parallel port, an IEEE 1394 serial port, a game port, a universal serial bus (USB) port, an IR interface, etc.\",\n \"A monitor 2144 or other type of display device can be also connected to the system bus 2108 via an interface, such as a video adapter 2146.It will also be appreciated that in alternative embodiments, a monitor 2144 can also be any display device (e.g., another computer having a display, a smart phone, a tablet computer, etc.)\",\n \"for receiving display information associated with computer 2102 via any communication means, including via the Internet and cloud-based networks.\",\n \"In addition to the monitor 2144, a computer typically comprises other peripheral output devices (not shown), such as speakers, printers, etc.\",\n \"The computer 2102 can operate in a networked environment using logical connections via wired and/or wireless communications to one or more remote computers, such as a remote computer(s) 2148.The remote computer(s) 2148 can be a workstation, a server computer, a router, a personal computer, portable computer, microprocessor-based entertainment appliance, a peer device or other common network node, and typically comprises many or all of the elements described relative to the computer 2102, although, for purposes of brevity, only a memory/storage device 2150 is illustrated.\",\n \"The logical connections depicted comprise wired/wireless connectivity to a local area network (LAN) 2152 and/or larger networks, e.g., a wide area network (WAN) 2154.Such LAN and WAN networking environments are commonplace in offices and companies, and facilitate enterprise-wide computer networks, such as intranets, all of which can connect to a global communications network, e.g., the Internet.\",\n \"When used in a LAN networking environment, the computer 2102 can be connected to the local network 2152 through a wired and/or wireless communication network interface or adapter 2156.The adapter 2156 can facilitate wired or wireless communication to the LAN 2152, which can also comprise a wireless AP disposed thereon for communicating with the wireless adapter 2156.When used in a WAN networking environment, the computer 2102 can comprise a modem 2158 or can be connected to a communications server on the WAN 2154 or has other means for establishing communications over the WAN 2154, such as by way of the Internet.\",\n \"The modem 2158, which can be internal or external and a wired or wireless device, can be connected to the system bus 2108 via the input device interface 2142.In a networked environment, program modules depicted relative to the computer 2102 or portions thereof, can be stored in the remote memory/storage device 2150.It will be appreciated that the network connections shown are example and other means of establishing a communications link between the computers can be used.\",\n \"The computer 2102 can be operable to communicate with any wireless devices or entities operatively disposed in wireless communication, e.g., a printer, scanner, desktop and/or portable computer, portable data assistant, communications satellite, any piece of equipment or location associated with a wirelessly detectable tag (e.g., a kiosk, news stand, restroom), and telephone.\",\n \"This can comprise Wireless Fidelity (Wi-Fi) and BLUETOOTH® wireless technologies.\",\n \"Thus, the communication can be a predefined structure as with a conventional network or simply an ad hoc communication between at least two devices.\",\n \"Wi-Fi can allow connection to the Internet from a couch at home, a bed in a hotel room or a conference room at work, without wires.\",\n \"Wi-Fi is a wireless technology similar to that used in a cell phone that enables such devices, e.g., computers, to send and receive data indoors and out; anywhere within the range of a base station.\",\n \"Wi-Fi networks use radio technologies called IEEE 802.11 (a, b, g, n, ac, ag etc.)\",\n \"to provide secure, reliable, fast wireless connectivity.\",\n \"A Wi-Fi network can be used to connect computers to each other, to the Internet, and to wired networks (which can use IEEE 802.3 or Ethernet).\",\n \"Wi-Fi networks operate in the unlicensed 2.4 and 5 GHz radio bands for example or with products that contain both bands (dual band), so the networks can provide real-world performance similar to the basic 10BaseT wired Ethernet networks used in many offices.\",\n \"FIG.\",\n \"22 presents an example embodiment 2200 of a mobile network platform 2210 that can implement and exploit one or more aspects of the disclosed subject matter described herein.\",\n \"In one or more embodiments, the mobile network platform 2210 can generate and receive signals transmitted and received by base stations (e.g., base station devices 1504, macrocell site 1502, or base stations 1614), central office (e.g., central office 1501 or 1611), or transmission device 101 or 102 associated with the disclosed subject matter.\",\n \"Generally, wireless network platform 2210 can comprise components, e.g., nodes, gateways, interfaces, servers, or disparate platforms, that facilitate both packet-switched (PS) (e.g., internet protocol (IP), frame relay, asynchronous transfer mode (ATM)) and circuit-switched (CS) traffic (e.g., voice and data), as well as control generation for networked wireless telecommunication.\",\n \"As a non-limiting example, wireless network platform 2210 can be included in telecommunications carrier networks, and can be considered carrier-side components as discussed elsewhere herein.\",\n \"Mobile network platform 2210 comprises CS gateway node(s) 2222 which can interface CS traffic received from legacy networks like telephony network(s) 2240 (e.g., public switched telephone network (PSTN), or public land mobile network (PLMN)) or a signaling system #7 (SS7) network 2270.Circuit switched gateway node(s) 2222 can authorize and authenticate traffic (e.g., voice) arising from such networks.\",\n \"Additionally, CS gateway node(s) 2222 can access mobility, or roaming, data generated through SS7 network 2270; for instance, mobility data stored in a visited location register (VLR), which can reside in memory 2230.Moreover, CS gateway node(s) 2222 interfaces CS-based traffic and signaling and PS gateway node(s) 2218.As an example, in a 3GPP UMTS network, CS gateway node(s) 2222 can be realized at least in part in gateway GPRS support node(s) (GGSN).\",\n \"It should be appreciated that functionality and specific operation of CS gateway node(s) 2222, PS gateway node(s) 2218, and serving node(s) 2216, is provided and dictated by radio technology(ies) utilized by mobile network platform 2210 for telecommunication.\",\n \"In addition to receiving and processing CS-switched traffic and signaling, PS gateway node(s) 2218 can authorize and authenticate PS-based data sessions with served mobile devices.\",\n \"Data sessions can comprise traffic, or content(s), exchanged with networks external to the wireless network platform 2210, like wide area network(s) (WANs) 2250, enterprise network(s) 2270, and service network(s) 2280, which can be embodied in local area network(s) (LANs), can also be interfaced with mobile network platform 2210 through PS gateway node(s) 2218.It is to be noted that WANs 2250 and enterprise network(s) 2260 can embody, at least in part, a service network(s) like IP multimedia subsystem (IMS).\",\n \"Based on radio technology layer(s) available in technology resource(s) 2217, packet-switched gateway node(s) 2218 can generate packet data protocol contexts when a data session is established; other data structures that facilitate routing of packetized data also can be generated.\",\n \"To that end, in an aspect, PS gateway node(s) 2218 can comprise a tunnel interface (e.g., tunnel termination gateway (TTG) in 3GPP UMTS network(s) (not shown)) which can facilitate packetized communication with disparate wireless network(s), such as Wi-Fi networks.\",\n \"In embodiment 2200, wireless network platform 2210 also comprises serving node(s) 2216 that, based upon available radio technology layer(s) within technology resource(s) 2217, convey the various packetized flows of data streams received through PS gateway node(s) 2218.It is to be noted that for technology resource(s) 2217 that rely primarily on CS communication, server node(s) can deliver traffic without reliance on PS gateway node(s) 2218; for example, server node(s) can embody at least in part a mobile switching center.\",\n \"As an example, in a 3GPP UMTS network, serving node(s) 2216 can be embodied in serving GPRS support node(s) (SGSN).\",\n \"For radio technologies that exploit packetized communication, server(s) 2214 in wireless network platform 2210 can execute numerous applications that can generate multiple disparate packetized data streams or flows, and manage (e.g., schedule, queue, format .\",\n \".\",\n \". )\",\n \"such flows.\",\n \"Such application(s) can comprise add-on features to standard services (for example, provisioning, billing, customer support .\",\n \".\",\n \". )\",\n \"provided by wireless network platform 2210.Data streams (e.g., content(s) that are part of a voice call or data session) can be conveyed to PS gateway node(s) 2218 for authorization/authentication and initiation of a data session, and to serving node(s) 2216 for communication thereafter.\",\n \"In addition to application server, server(s) 2214 can comprise utility server(s), a utility server can comprise a provisioning server, an operations and maintenance server, a security server that can implement at least in part a certificate authority and firewalls as well as other security mechanisms, and the like.\",\n \"In an aspect, security server(s) secure communication served through wireless network platform 2210 to ensure network's operation and data integrity in addition to authorization and authentication procedures that CS gateway node(s) 2222 and PS gateway node(s) 2218 can enact.\",\n \"Moreover, provisioning server(s) can provision services from external network(s) like networks operated by a disparate service provider; for instance, WAN 2250 or Global Positioning System (GPS) network(s) (not shown).\",\n \"Provisioning server(s) can also provision coverage through networks associated to wireless network platform 2210 (e.g., deployed and operated by the same service provider), such as the distributed antennas networks shown in FIG.\",\n \"1(s) that enhance wireless service coverage by providing more network coverage.\",\n \"Repeater devices such as those shown in FIGS.\",\n \"7, 8, and 9 also improve network coverage in order to enhance subscriber service experience by way of UE 2275.It is to be noted that server(s) 2214 can comprise one or more processors configured to confer at least in part the functionality of macro network platform 2210.To that end, the one or more processor can execute code instructions stored in memory 2230, for example.\",\n \"It is should be appreciated that server(s) 2214 can comprise a content manager 2215, which operates in substantially the same manner as described hereinbefore.\",\n \"In example embodiment 2200, memory 2230 can store information related to operation of wireless network platform 2210.Other operational information can comprise provisioning information of mobile devices served through wireless platform network 2210, subscriber databases; application intelligence, pricing schemes, e.g., promotional rates, flat-rate programs, couponing campaigns; technical specification(s) consistent with telecommunication protocols for operation of disparate radio, or wireless, technology layers; and so forth.\",\n \"Memory 2230 can also store information from at least one of telephony network(s) 2240, WAN 2250, enterprise network(s) 2270, or SS7 network 2260.In an aspect, memory 2230 can be, for example, accessed as part of a data store component or as a remotely connected memory store.\",\n \"In order to provide a context for the various aspects of the disclosed subject matter, FIG.\",\n \"22, and the following discussion, are intended to provide a brief, general description of a suitable environment in which the various aspects of the disclosed subject matter can be implemented.\",\n \"While the subject matter has been described above in the general context of computer-executable instructions of a computer program that runs on a computer and/or computers, those skilled in the art will recognize that the disclosed subject matter also can be implemented in combination with other program modules.\",\n \"Generally, program modules comprise routines, programs, components, data structures, etc.\",\n \"that perform particular tasks and/or implement particular abstract data types.\",\n \"FIG.\",\n \"23 depicts an illustrative embodiment of a communication device 2300.The communication device 2300 can serve as an illustrative embodiment of devices such as mobile devices and in-building devices referred to by the subject disclosure (e.g., in FIGS.\",\n \"15, 16A-16C).\",\n \"The communication device 2300 can comprise a wireline and/or wireless transceiver 2302 (herein transceiver 2302), a user interface (UI) 2304, a power supply 2314, a location receiver 2316, a motion sensor 2318, an orientation sensor 2320, and a controller 2306 for managing operations thereof.\",\n \"The transceiver 2302 can support short-range or long-range wireless access technologies such as Bluetooth®, ZigBee®, WiFi, DECT, or cellular communication technologies, just to mention a few (Bluetooth® and ZigBee® are trademarks registered by the Bluetooth® Special Interest Group and the ZigBee® Alliance, respectively).\",\n \"Cellular technologies can include, for example, CDMA-1×, UMTS/HSDPA, GSM/GPRS, TDMA/EDGE, EV/DO, WiMAX, SDR, LTE, as well as other next generation wireless communication technologies as they arise.\",\n \"The transceiver 2302 can also be adapted to support circuit-switched wireline access technologies (such as PSTN), packet-switched wireline access technologies (such as TCP/IP, VoIP, etc.\",\n \"), and combinations thereof.\",\n \"The UI 2304 can include a depressible or touch-sensitive keypad 2308 with a navigation mechanism such as a roller ball, a joystick, a mouse, or a navigation disk for manipulating operations of the communication device 2300.The keypad 2308 can be an integral part of a housing assembly of the communication device 2300 or an independent device operably coupled thereto by a tethered wireline interface (such as a USB cable) or a wireless interface supporting for example Bluetooth®.\",\n \"The keypad 2308 can represent a numeric keypad commonly used by phones, and/or a QWERTY keypad with alphanumeric keys.\",\n \"The UI 2304 can further include a display 2310 such as monochrome or color LCD (Liquid Crystal Display), OLED (Organic Light Emitting Diode) or other suitable display technology for conveying images to an end user of the communication device 2300.In an embodiment where the display 2310 is touch-sensitive, a portion or all of the keypad 2308 can be presented by way of the display 2310 with navigation features.\",\n \"The display 2310 can use touch screen technology to also serve as a user interface for detecting user input.\",\n \"As a touch screen display, the communication device 2300 can be adapted to present a user interface having graphical user interface (GUI) elements that can be selected by a user with a touch of a finger.\",\n \"The touch screen display 2310 can be equipped with capacitive, resistive or other forms of sensing technology to detect how much surface area of a user's finger has been placed on a portion of the touch screen display.\",\n \"This sensing information can be used to control the manipulation of the GUI elements or other functions of the user interface.\",\n \"The display 2310 can be an integral part of the housing assembly of the communication device 2300 or an independent device communicatively coupled thereto by a tethered wireline interface (such as a cable) or a wireless interface.\",\n \"The UI 2304 can also include an audio system 2312 that utilizes audio technology for conveying low volume audio (such as audio heard in proximity of a human ear) and high volume audio (such as speakerphone for hands free operation).\",\n \"The audio system 2312 can further include a microphone for receiving audible signals of an end user.\",\n \"The audio system 2312 can also be used for voice recognition applications.\",\n \"The UI 2304 can further include an image sensor 2313 such as a charged coupled device (CCD) camera for capturing still or moving images.\",\n \"The power supply 2314 can utilize common power management technologies such as replaceable and rechargeable batteries, supply regulation technologies, and/or charging system technologies for supplying energy to the components of the communication device 2300 to facilitate long-range or short-range portable communications.\",\n \"Alternatively, or in combination, the charging system can utilize external power sources such as DC power supplied over a physical interface such as a USB port or other suitable tethering technologies.\",\n \"The location receiver 2316 can utilize location technology such as a global positioning system (GPS) receiver capable of assisted GPS for identifying a location of the communication device 2300 based on signals generated by a constellation of GPS satellites, which can be used for facilitating location services such as navigation.\",\n \"The motion sensor 2318 can utilize motion sensing technology such as an accelerometer, a gyroscope, or other suitable motion sensing technology to detect motion of the communication device 2300 in three-dimensional space.\",\n \"The orientation sensor 2320 can utilize orientation sensing technology such as a magnetometer to detect the orientation of the communication device 2300 (north, south, west, and east, as well as combined orientations in degrees, minutes, or other suitable orientation metrics).\",\n \"The communication device 2300 can use the transceiver 2302 to also determine a proximity to a cellular, WiFi, Bluetooth®, or other wireless access points by sensing techniques such as utilizing a received signal strength indicator (RSSI) and/or signal time of arrival (TOA) or time of flight (TOF) measurements.\",\n \"The controller 2306 can utilize computing technologies such as a microprocessor, a digital signal processor (DSP), programmable gate arrays, application specific integrated circuits, and/or a video processor with associated storage memory such as Flash, ROM, RAM, SRAM, DRAM or other storage technologies for executing computer instructions, controlling, and processing data supplied by the aforementioned components of the communication device 2300.Other components not shown in FIG.\",\n \"23 can be used in one or more embodiments of the subject disclosure.\",\n \"For instance, the communication device 2300 can include a slot for adding or removing an identity module such as a Subscriber Identity Module (SIM) card or Universal Integrated Circuit Card (UICC).\",\n \"SIM or UICC cards can be used for identifying subscriber services, executing programs, storing subscriber data, and so on.\",\n \"In the subject specification, terms such as “store,” “storage,” “data store,” data storage,” “database,” and substantially any other information storage component relevant to operation and functionality of a component, refer to “memory components,” or entities embodied in a “memory” or components comprising the memory.\",\n \"It will be appreciated that the memory components described herein can be either volatile memory or nonvolatile memory, or can comprise both volatile and nonvolatile memory, by way of illustration, and not limitation, volatile memory, non-volatile memory, disk storage, and memory storage.\",\n \"Further, nonvolatile memory can be included in read only memory (ROM), programmable ROM (PROM), electrically programmable ROM (EPROM), electrically erasable ROM (EEPROM), or flash memory.\",\n \"Volatile memory can comprise random access memory (RAM), which acts as external cache memory.\",\n \"By way of illustration and not limitation, RAM is available in many forms such as synchronous RAM (SRAM), dynamic RAM (DRAM), synchronous DRAM (SDRAM), double data rate SDRAM (DDR SDRAM), enhanced SDRAM (ESDRAM), Synchlink DRAM (SLDRAM), and direct Rambus RAM (DRRAM).\",\n \"Additionally, the disclosed memory components of systems or methods herein are intended to comprise, without being limited to comprising, these and any other suitable types of memory.\",\n \"Moreover, it will be noted that the disclosed subject matter can be practiced with other computer system configurations, comprising single-processor or multiprocessor computer systems, mini-computing devices, mainframe computers, as well as personal computers, hand-held computing devices (e.g., PDA, phone, smartphone, watch, tablet computers, netbook computers, etc.\",\n \"), microprocessor-based or programmable consumer or industrial electronics, and the like.\",\n \"The illustrated aspects can also be practiced in distributed computing environments where tasks are performed by remote processing devices that are linked through a communications network; however, some if not all aspects of the subject disclosure can be practiced on stand-alone computers.\",\n \"In a distributed computing environment, program modules can be located in both local and remote memory storage devices.\",\n \"Some of the embodiments described herein can also employ artificial intelligence (AI) to facilitate automating one or more features described herein.\",\n \"For example, artificial intelligence can be used in optional training controller 230 evaluate and select candidate frequencies, modulation schemes, MIMO modes, and/or guided wave modes in order to maximize transfer efficiency.\",\n \"The embodiments (e.g., in connection with automatically identifying acquired cell sites that provide a maximum value/benefit after addition to an existing communication network) can employ various AI-based schemes for carrying out various embodiments thereof.\",\n \"Moreover, the classifier can be employed to determine a ranking or priority of the each cell site of the acquired network.\",\n \"A classifier is a function that maps an input attribute vector, x=(x1, x2, x3, x4, .\",\n \".\",\n \".\",\n \", xn), to a confidence that the input belongs to a class, that is, f(x)=confidence (class).\",\n \"Such classification can employ a probabilistic and/or statistical-based analysis (e.g., factoring into the analysis utilities and costs) to prognose or infer an action that a user desires to be automatically performed.\",\n \"A support vector machine (SVM) is an example of a classifier that can be employed.\",\n \"The SVM operates by finding a hypersurface in the space of possible inputs, which the hypersurface attempts to split the triggering criteria from the non-triggering events.\",\n \"Intuitively, this makes the classification correct for testing data that is near, but not identical to training data.\",\n \"Other directed and undirected model classification approaches comprise, e.g., naïve Bayes, Bayesian networks, decision trees, neural networks, fuzzy logic models, and probabilistic classification models providing different patterns of independence can be employed.\",\n \"Classification as used herein also is inclusive of statistical regression that is utilized to develop models of priority.\",\n \"As will be readily appreciated, one or more of the embodiments can employ classifiers that are explicitly trained (e.g., via a generic training data) as well as implicitly trained (e.g., via observing UE behavior, operator preferences, historical information, receiving extrinsic information).\",\n \"For example, SVMs can be configured via a learning or training phase within a classifier constructor and feature selection module.\",\n \"Thus, the classifier(s) can be used to automatically learn and perform a number of functions, including but not limited to determining according to a predetermined criteria which of the acquired cell sites will benefit a maximum number of subscribers and/or which of the acquired cell sites will add minimum value to the existing communication network coverage, etc.\",\n \"As used in some contexts in this application, in some embodiments, the terms “component,” “system” and the like are intended to refer to, or comprise, a computer-related entity or an entity related to an operational apparatus with one or more specific functionalities, wherein the entity can be either hardware, a combination of hardware and software, software, or software in execution.\",\n \"As an example, a component may be, but is not limited to being, a process running on a processor, a processor, an object, an executable, a thread of execution, computer-executable instructions, a program, and/or a computer.\",\n \"By way of illustration and not limitation, both an application running on a server and the server can be a component.\",\n \"One or more components may reside within a process and/or thread of execution and a component may be localized on one computer and/or distributed between two or more computers.\",\n \"In addition, these components can execute from various computer readable media having various data structures stored thereon.\",\n \"The components may communicate via local and/or remote processes such as in accordance with a signal having one or more data packets (e.g., data from one component interacting with another component in a local system, distributed system, and/or across a network such as the Internet with other systems via the signal).\",\n \"As another example, a component can be an apparatus with specific functionality provided by mechanical parts operated by electric or electronic circuitry, which is operated by a software or firmware application executed by a processor, wherein the processor can be internal or external to the apparatus and executes at least a part of the software or firmware application.\",\n \"As yet another example, a component can be an apparatus that provides specific functionality through electronic components without mechanical parts, the electronic components can comprise a processor therein to execute software or firmware that confers at least in part the functionality of the electronic components.\",\n \"While various components have been illustrated as separate components, it will be appreciated that multiple components can be implemented as a single component, or a single component can be implemented as multiple components, without departing from example embodiments.\",\n \"Further, the various embodiments can be implemented as a method, apparatus or article of manufacture using standard programming and/or engineering techniques to produce software, firmware, hardware or any combination thereof to control a computer to implement the disclosed subject matter.\",\n \"The term “article of manufacture” as used herein is intended to encompass a computer program accessible from any computer-readable device or computer-readable storage/communications media.\",\n \"For example, computer readable storage media can include, but are not limited to, magnetic storage devices (e.g., hard disk, floppy disk, magnetic strips), optical disks (e.g., compact disk (CD), digital versatile disk (DVD)), smart cards, and flash memory devices (e.g., card, stick, key drive).\",\n \"Of course, those skilled in the art will recognize many modifications can be made to this configuration without departing from the scope or spirit of the various embodiments.\",\n \"In addition, the words “example” and “exemplary” are used herein to mean serving as an instance or illustration.\",\n \"Any embodiment or design described herein as “example” or “exemplary” is not necessarily to be construed as preferred or advantageous over other embodiments or designs.\",\n \"Rather, use of the word example or exemplary is intended to present concepts in a concrete fashion.\",\n \"As used in this application, the term “or” is intended to mean an inclusive “or” rather than an exclusive “or”.\",\n \"That is, unless specified otherwise or clear from context, “X employs A or B” is intended to mean any of the natural inclusive permutations.\",\n \"That is, if X employs A; X employs B; or X employs both A and B, then “X employs A or B” is satisfied under any of the foregoing instances.\",\n \"In addition, the articles “a” and “an” as used in this application and the appended claims should generally be construed to mean “one or more” unless specified otherwise or clear from context to be directed to a singular form.\",\n \"Moreover, terms such as “user equipment,” “mobile station,” “mobile,” subscriber station,” “access terminal,” “terminal,” “handset,” “mobile device” (and/or terms representing similar terminology) can refer to a wireless device utilized by a subscriber or user of a wireless communication service to receive or convey data, control, voice, video, sound, gaming or substantially any data-stream or signaling-stream.\",\n \"The foregoing terms are utilized interchangeably herein and with reference to the related drawings.\",\n \"Furthermore, the terms “user,” “subscriber,” “customer,” “consumer” and the like are employed interchangeably throughout, unless context warrants particular distinctions among the terms.\",\n \"It should be appreciated that such terms can refer to human entities or automated components supported through artificial intelligence (e.g., a capacity to make inference based, at least, on complex mathematical formalisms), which can provide simulated vision, sound recognition and so forth.\",\n \"As employed herein, the term “processor” can refer to substantially any computing processing unit or device comprising, but not limited to comprising, single-core processors; single-processors with software multithread execution capability; multi-core processors; multi-core processors with software multithread execution capability; multi-core processors with hardware multithread technology; parallel platforms; and parallel platforms with distributed shared memory.\",\n \"Additionally, a processor can refer to an integrated circuit, an application specific integrated circuit (ASIC), a digital signal processor (DSP), a field programmable gate array (FPGA), a programmable logic controller (PLC), a complex programmable logic device (CPLD), a discrete gate or transistor logic, discrete hardware components or any combination thereof designed to perform the functions described herein.\",\n \"Processors can exploit nano-scale architectures such as, but not limited to, molecular and quantum-dot based transistors, switches and gates, in order to optimize space usage or enhance performance of user equipment.\",\n \"A processor can also be implemented as a combination of computing processing units.\",\n \"As used herein, terms such as “data storage,” data storage,” “database,” and substantially any other information storage component relevant to operation and functionality of a component, refer to “memory components,” or entities embodied in a “memory” or components comprising the memory.\",\n \"It will be appreciated that the memory components or computer-readable storage media, described herein can be either volatile memory or nonvolatile memory or can include both volatile and nonvolatile memory.\",\n \"What has been described above includes mere examples of various embodiments.\",\n \"It is, of course, not possible to describe every conceivable combination of components or methodologies for purposes of describing these examples, but one of ordinary skill in the art can recognize that many further combinations and permutations of the present embodiments are possible.\",\n \"Accordingly, the embodiments disclosed and/or claimed herein are intended to embrace all such alterations, modifications and variations that fall within the spirit and scope of the appended claims.\",\n \"Furthermore, to the extent that the term “includes” is used in either the detailed description or the claims, such term is intended to be inclusive in a manner similar to the term “comprising” as “comprising” is interpreted when employed as a transitional word in a claim.\",\n \"In addition, a flow diagram may include a “start” and/or “continue” indication.\",\n \"The “start” and “continue” indications reflect that the steps presented can optionally be incorporated in or otherwise used in conjunction with other routines.\",\n \"In this context, “start” indicates the beginning of the first step presented and may be preceded by other activities not specifically shown.\",\n \"Further, the “continue” indication reflects that the steps presented may be performed multiple times and/or may be succeeded by other activities not specifically shown.\",\n \"Further, while a flow diagram indicates a particular ordering of steps, other orderings are likewise possible provided that the principles of causality are maintained.\",\n \"As may also be used herein, the term(s) “operably coupled to”, “coupled to”, and/or “coupling” includes direct coupling between items and/or indirect coupling between items via one or more intervening items.\",\n \"Such items and intervening items include, but are not limited to, junctions, communication paths, components, circuit elements, circuits, functional blocks, and/or devices.\",\n \"As an example of indirect coupling, a signal conveyed from a first item to a second item may be modified by one or more intervening items by modifying the form, nature or format of information in a signal, while one or more elements of the information in the signal are nevertheless conveyed in a manner than can be recognized by the second item.\",\n \"In a further example of indirect coupling, an action in a first item can cause a reaction on the second item, as a result of actions and/or reactions in one or more intervening items.\",\n \"Although specific embodiments have been illustrated and described herein, it should be appreciated that any arrangement which achieves the same or similar purpose may be substituted for the embodiments described or shown by the subject disclosure.\",\n \"The subject disclosure is intended to cover any and all adaptations or variations of various embodiments.\",\n \"Combinations of the above embodiments, and other embodiments not specifically described herein, can be used in the subject disclosure.\",\n \"For instance, one or more features from one or more embodiments can be combined with one or more features of one or more other embodiments.\",\n \"In one or more embodiments, features that are positively recited can also be negatively recited and excluded from the embodiment with or without replacement by another structural and/or functional feature.\",\n \"The steps or functions described with respect to the embodiments of the subject disclosure can be performed in any order.\",\n \"The steps or functions described with respect to the embodiments of the subject disclosure can be performed alone or in combination with other steps or functions of the subject disclosure, as well as from other embodiments or from other steps that have not been described in the subject disclosure.\",\n \"Further, more than or less than all of the features described with respect to an embodiment can also be utilized.\"\n ]\n]"},"source":{"kind":"string","value":"Patent_15872029"}}},{"rowIdx":4493989,"cells":{"text":{"kind":"list like","value":[["DATA ACQUISITION DEVICES, SYSTEMS AND METHOD FOR ANALYZING PASSIVE STRAIN INDICATORS AND MONITORING TURBINE COMPONENT STRAIN","Data acquisition devices for analyzing reference objects and systems for monitoring turbine component deformation are provided.","A data acquisition device has a longitudinal axis and includes a lens assembly and an image capture device in communication with the lens assembly for receiving and processing light from the lens assembly to generate images.","The data acquisition device further includes a light source and a light tube coupled at a rear end to the light source.","The light tube extends along the longitudinal axis between a front end and the rear end, and is operable to transport light from the light source therethrough and emit the light from the front end.","The data acquisition device further includes an actuator operable to activate the image capture device and the light source."],["1.A system for monitoring turbine component deformation, the turbine component having an exterior surface, the system comprising: a passive strain indicator configurable on the exterior surface of the turbine component; and a data acquisition device for analyzing the passive strain indicator, the data acquisition device comprising: a lens assembly; an image capture device in communication with the lens assembly for receiving and processing light from the lens assembly to generate images; a light source; a light tube coupled at a rear end to the light source and extending along a longitudinal axis between a front end and the rear end, the light tube operable to transport light from the light source therethrough and emit the light from the front end; an actuator operable to activate the image capture device and the light source; a shell, the shell surrounding the lens assembly, the image capture device, the light source, and the light tube; and a plurality of spacers disposed proximate the front end of the light tube, each of the plurality of spacers extending from the shell and sized to space the front end of the light tube from the exterior surface of the turbine component when the data acquisition device is in an operative position in contact with the exterior surface of the turbine component.","2.The system of claim 1, wherein the data acquisition device further comprises an outer shroud surrounding at least a portion of an outer surface of the light tube.","3.The system of claim 1, wherein an outer surface of the light tube comprises a chamfered portion, the chamfered portion tapering towards an inner surface of the light tube along the longitudinal axis.","4.The system of claim 3, wherein the chamfered portion includes the front end.","5.The system of claim 1, wherein light is emitted from the front end of the light tube at an angle of incidence of between approximately 20 degrees and approximately 50 degrees.","6.The system of claim 1, wherein each of the plurality of spacers is sized to space the front end of the light tube from the exterior surface of the turbine component by a distance along the longitudinal axis of between approximately 0.25 inches and approximately 0.75 inches when the data acquisition device is in an operative position in contact with the exterior surface of the turbine component.","7.The system of claim 1, wherein the data acquisition device further comprises a processor, the processor configured for: locating a passive strain indicator portion relative to a background portion within an image of the passive strain indicator by performing a first analysis of the image; identifying passive strain indicator indicia of the passive strain indicator portion by performing a second analysis of the image; and conducting a quality analysis of the passive strain indicator portion by performing a third analysis of the passive strain indicator portion of the image, the third analysis utilizing a higher bit-depth than the first analysis.","8.A method for analyzing a passive strain indicator, the method comprising: locating a passive strain indicator portion relative to a background portion within an image of the passive strain indicator by performing a first analysis of the image; identifying passive strain indicator indicia of the passive strain indicator portion by performing a second analysis of the image; and conducting a quality analysis of the passive strain indicator portion by performing a third analysis of the passive strain indicator portion of the image, the third analysis utilizing a higher bit-depth than the first analysis.","9.The method of claim 16, wherein the first analysis is a binary analysis of multi-pixel groups of the passive strain indicator portion of the image.","10.The method of claim 16, wherein the second analysis is a binary analysis of single pixels of the passive strain indicator portion of the image.","11.The method of claim 16, wherein the third analysis is a 256 bit-per-pixel greyscale analysis.","12.The method of claim 16, further comprising the step of activating a light source.","13.The method of claim 16, further comprising the step of saving the image when the locating step, the identifying step, and the conducting step each satisfy a predetermined threshold.","14.The method of claim 21, further comprising comparing the image to a previously-saved image."],[" BACKGROUND OF THE INVENTION Turbomachines are widely utilized in fields such as power generation and aircraft engines.","For example, a conventional gas turbine system includes a compressor section, a combustor section, and at least one turbine section.","The compressor section is configured to compress air as the air flows through the compressor section.","The air is then flowed from the compressor section to the combustor section, where it is mixed with fuel and combusted, generating a hot gas flow.","The hot gas flow is provided to the turbine section, which utilizes the hot gas flow by extracting energy from it to power the compressor, an electrical generator, and other various loads.","During operation of a turbomachine, various components (collectively known as turbine components) within the turbomachine and particularly within the turbine section of the turbomachine, such as turbine blades, may be subject to creep due to high temperatures and stresses.","For turbine blades, creep may cause portions of or the entire blade to elongate so that the blade tips contact a stationary structure, for example a turbine casing, and potentially cause unwanted vibrations and/or reduced performance during operation.","Accordingly, it is desirable to monitor turbine components for creep.","One approach to monitoring turbine components for creep is to configure passive strain indicators on the components, and analyze the passive strain indicators at various intervals to monitor for deformations associated with creep strain.","However, such deformation can in many cases be on the order of 0.01% of an original dimension, thus requiring specialized equipment for strain monitoring.","Presently known acquisition tools and techniques for monitoring such passive strain indicators may in some cases not provide the desired sufficiently low-distortion, high-contrast, small scale images for these applications.","Accordingly, alternative systems and methods for monitoring turbine component strain are desired in the art.","Further, alternative data acquisition devices and methods for analyzing reference objects, such as passive strain indicators, are desired in the art.","Systems, devices and methods which provide sufficiently low-distortion, high-contrast, small scale images for turbine component passive strain indicator monitoring would be particularly advantageous."],[" BRIEF DESCRIPTION OF THE INVENTION Aspects and advantages of the invention will be set forth in part in the following description, or may be obvious from the description, or may be learned through practice of the invention.","In accordance with one embodiment of the present disclosure, a data acquisition device for analyzing a reference object is provided.","The data acquisition device has a longitudinal axis and includes a lens assembly and an image capture device in communication with the lens assembly for receiving and processing light from the lens assembly to generate images.","The data acquisition device further includes a light source and a light tube coupled at a rear end to the light source.","The light tube extends along the longitudinal axis between a front end and the rear end, and is operable to transport light from the light source therethrough and emit the light from the front end.","The data acquisition device further includes an actuator operable to activate the image capture device and the light source.","In accordance with another embodiment of the present disclosure, a system for monitoring turbine component deformation is provided.","The turbine component has an exterior surface.","The system includes a passive strain indicator configurable on the exterior surface of the turbine component, and a data acquisition device for analyzing the passive strain indicator.","The data acquisition device includes a lens assembly and an image capture device in communication with the lens assembly for receiving and processing light from the lens assembly to generate images.","The data acquisition device further includes a light source, and a light tube coupled at a rear end to the light source.","The light tube extends along a longitudinal axis between a front end and the rear end, and is operable to transport light from the light source therethrough and emit the light from the front end.","The data acquisition device further includes an actuator operable to activate the image capture device and the light source, and a shell, the shell surrounding the lens assembly, the image capture device, the light source, and the light tube.","The data acquisition device further includes a plurality of spacers disposed proximate the front end of the light tube.","Each of the plurality of spacers extends from the shell and is sized to space the front end of the light tube from the exterior surface of the turbine component when the data acquisition device is in an operative position in contact with the exterior surface of the turbine component.","In accordance with another embodiment of the present disclosure, a method for analyzing a passive strain indicator is provided.","The method includes locating a passive strain indicator portion relative to a background portion within an image of the passive strain indicator by performing a first analysis of the image.","The method further includes identifying passive strain indicator indicia of the passive strain indicator portion by performing a second analysis of the image.","The method further includes conducting a quality analysis of the passive strain indicator portion by performing a third analysis of the passive strain indicator portion of the image, the third analysis utilizing a higher bit-depth than the first analysis.","These and other features, aspects and advantages of the present invention will become better understood with reference to the following description and appended claims.","The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and, together with the description, serve to explain the principles of the invention."],["CROSS-REFERENCE TO RELATED PATENT APPLICATIONS This application is a continuation-in-part of application Ser.","No.","15/384,513 filed Dec. 20, 2016 and titled “Data Acquisition Devices, Systems and Method for Analyzing Passing Strain Indicators and Monitoring Turbine Component Strain”, which is incorporated by reference herein.","FIELD OF THE INVENTION The present disclosure relates generally to data acquisition devices and methods for analyzing reference objects such as passive strain indicators, and to systems for monitoring turbine component strain which utilize such devices to analyze passive strain indicators.","BACKGROUND OF THE INVENTION Turbomachines are widely utilized in fields such as power generation and aircraft engines.","For example, a conventional gas turbine system includes a compressor section, a combustor section, and at least one turbine section.","The compressor section is configured to compress air as the air flows through the compressor section.","The air is then flowed from the compressor section to the combustor section, where it is mixed with fuel and combusted, generating a hot gas flow.","The hot gas flow is provided to the turbine section, which utilizes the hot gas flow by extracting energy from it to power the compressor, an electrical generator, and other various loads.","During operation of a turbomachine, various components (collectively known as turbine components) within the turbomachine and particularly within the turbine section of the turbomachine, such as turbine blades, may be subject to creep due to high temperatures and stresses.","For turbine blades, creep may cause portions of or the entire blade to elongate so that the blade tips contact a stationary structure, for example a turbine casing, and potentially cause unwanted vibrations and/or reduced performance during operation.","Accordingly, it is desirable to monitor turbine components for creep.","One approach to monitoring turbine components for creep is to configure passive strain indicators on the components, and analyze the passive strain indicators at various intervals to monitor for deformations associated with creep strain.","However, such deformation can in many cases be on the order of 0.01% of an original dimension, thus requiring specialized equipment for strain monitoring.","Presently known acquisition tools and techniques for monitoring such passive strain indicators may in some cases not provide the desired sufficiently low-distortion, high-contrast, small scale images for these applications.","Accordingly, alternative systems and methods for monitoring turbine component strain are desired in the art.","Further, alternative data acquisition devices and methods for analyzing reference objects, such as passive strain indicators, are desired in the art.","Systems, devices and methods which provide sufficiently low-distortion, high-contrast, small scale images for turbine component passive strain indicator monitoring would be particularly advantageous.","BRIEF DESCRIPTION OF THE INVENTION Aspects and advantages of the invention will be set forth in part in the following description, or may be obvious from the description, or may be learned through practice of the invention.","In accordance with one embodiment of the present disclosure, a data acquisition device for analyzing a reference object is provided.","The data acquisition device has a longitudinal axis and includes a lens assembly and an image capture device in communication with the lens assembly for receiving and processing light from the lens assembly to generate images.","The data acquisition device further includes a light source and a light tube coupled at a rear end to the light source.","The light tube extends along the longitudinal axis between a front end and the rear end, and is operable to transport light from the light source therethrough and emit the light from the front end.","The data acquisition device further includes an actuator operable to activate the image capture device and the light source.","In accordance with another embodiment of the present disclosure, a system for monitoring turbine component deformation is provided.","The turbine component has an exterior surface.","The system includes a passive strain indicator configurable on the exterior surface of the turbine component, and a data acquisition device for analyzing the passive strain indicator.","The data acquisition device includes a lens assembly and an image capture device in communication with the lens assembly for receiving and processing light from the lens assembly to generate images.","The data acquisition device further includes a light source, and a light tube coupled at a rear end to the light source.","The light tube extends along a longitudinal axis between a front end and the rear end, and is operable to transport light from the light source therethrough and emit the light from the front end.","The data acquisition device further includes an actuator operable to activate the image capture device and the light source, and a shell, the shell surrounding the lens assembly, the image capture device, the light source, and the light tube.","The data acquisition device further includes a plurality of spacers disposed proximate the front end of the light tube.","Each of the plurality of spacers extends from the shell and is sized to space the front end of the light tube from the exterior surface of the turbine component when the data acquisition device is in an operative position in contact with the exterior surface of the turbine component.","In accordance with another embodiment of the present disclosure, a method for analyzing a passive strain indicator is provided.","The method includes locating a passive strain indicator portion relative to a background portion within an image of the passive strain indicator by performing a first analysis of the image.","The method further includes identifying passive strain indicator indicia of the passive strain indicator portion by performing a second analysis of the image.","The method further includes conducting a quality analysis of the passive strain indicator portion by performing a third analysis of the passive strain indicator portion of the image, the third analysis utilizing a higher bit-depth than the first analysis.","These and other features, aspects and advantages of the present invention will become better understood with reference to the following description and appended claims.","The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and, together with the description, serve to explain the principles of the invention.","BRIEF DESCRIPTION OF THE DRAWINGS A full and enabling disclosure of the present invention, including the best mode thereof, directed to one of ordinary skill in the art, is set forth in the specification, which makes reference to the appended figures, in which: FIG.","1 is a perspective view of an exemplary turbine component comprising a passive strain indicator in accordance with one embodiment of the present disclosure; FIG.","2 is a top view of an exemplary passive strain indicator in accordance with one embodiment of the present disclosure; FIG.","3 is a side view of a system for monitoring turbine component strain in accordance with one embodiment of the present disclosure; FIG.","4 is a perspective view of a data acquisition device in accordance with one embodiment of the present disclosure; FIG.","5 is a perspective cross-sectional view of a data acquisition device in accordance with one embodiment of the present disclosure; FIG.","6 is a side view of a data acquisition device, with various components shown in shadow for illustrative purposes, in accordance with one embodiment of the present disclosure; FIG.","7 is a perspective view of a light tube of a data acquisition device in accordance with one embodiment of the present disclosure; FIG.","8 illustrates an image of a passive strain indicator in accordance with one embodiment of the present disclosure; and FIG.","9 is a flow chart illustrating a method in accordance with one embodiment of the present disclosure.","DETAILED DESCRIPTION OF THE INVENTION Reference now will be made in detail to embodiments of the invention, one or more examples of which are illustrated in the drawings.","Each example is provided by way of explanation of the invention, not limitation of the invention.","In fact, it will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the scope or spirit of the invention.","For instance, features illustrated or described as part of one embodiment can be used with another embodiment to yield a still further embodiment.","Thus, it is intended that the present invention covers such modifications and variations as come within the scope of the appended claims and their equivalents.","Referring now to FIG.","1, a turbine component 10 is illustrated with a passive strain indicator 40 configured on a portion of the turbine component's exterior surface 11.The turbine component 10 can comprise a variety of specific components such as those utilized in high temperature applications (e.g., components comprising nickel or cobalt based superalloys).","For example, in some embodiments, the turbine component 10 may comprise a combustion component or hot gas path component.","In some particular embodiments, the turbine component 10 may comprise a bucket, blade, vane, nozzle, shroud, rotor, transition piece or casing.","In other embodiments, the turbine component 10 may comprise any other component of a turbine such as a component for a gas turbine, industrial gas turbine, steam turbine or the like.","The turbine component 10 has an exterior surface 11 on which passive strain indicators 40 are configured.","Passive strain indicators 40 in accordance with the present disclosure may be configured on the exterior surface 11 using any suitable techniques, including deposition techniques; other suitable additive manufacturing techniques; subtractive techniques such as laser ablation, engraving, machining, etc.","; appearance- change techniques such as annealing, direct surface discoloration, or techniques to cause local changes in reflectivity; mounting of previously formed passive strain indicators 40 using suitable mounting apparatus or techniques such as adhering, welding, brazing, etc.","; or identifying pre-existing characteristics of the exterior surface 11 that can function as the components of a passive strain indicator 40.Referring now to FIGS.","1 and 2, a passive strain indicator 40 is configured on a portion of the exterior surface 11 of the turbine component 10.The passive strain indicator 40 generally comprises at least two reference points 41 and 42 that can be used to measure a distance D between said at least two reference points 41 and 42 at a plurality of time intervals.","As should be appreciated to those skilled in the art, these measurements can help determine the amount of strain, strain rate, creep, fatigue, stress, etc.","at that region of the turbine component 10.The at least two reference points 41 and 42 can be disposed at a variety of distances and in a variety of locations depending on the specific turbine component 10 so long as the distance D there between can be measured.","Moreover, the at least two reference points 41 and 42 may comprise dots, lines, circles, boxes or any other geometrical or non-geometrical shape so long as they are consistently identifiable and may be used to measure the distance D there between.","The passive strain indicator 40 may comprise a variety of different configurations and cross-sections such as by incorporating a variety of differently shaped, sized, and positioned reference points 41 and 42.For example, as illustrated in FIG.","2, the passive strain indicator 40 may comprise a variety of different reference points comprising various shapes and sizes.","Such embodiments may provide for a greater variety of distance measurements D such as between the outer most reference points (as illustrated), between two internal or external reference points, or any combination there between.","The greater variety may further provide a more robust strain analysis on a particular portion of the turbine component 10 by providing strain measurements across a greater variety of locations.","Furthermore, the dimensions of the passive strain indicator 40 may depend on, for example, the turbine component 10, the location of the passive strain indicator 40, the targeted precision of the measurement, application technique, and optical measurement technique.","For example, in some embodiments, the passive strain indicator 40 may comprise a length and width ranging from less than 1 millimeter to greater than 300 millimeters.","Moreover, the passive strain indicator 40 may comprise any thickness that is suitable for application and subsequent optical identification without significantly impacting the performance of the underlying turbine component 10.Notably, this thickness may be a positive thickness away from the surface 11 (such as when additive techniques are utilized) or a negative thickness into the surface 11 (such as when subtractive techniques are utilized).","For example, in some embodiments, the passive strain indicator 40 may comprise a thickness of less than from about 0.01 millimeters to greater than 1 millimeter.","In some embodiments, the passive strain indicator 40 may have a substantially uniform thickness.","Such embodiments may help facilitate more accurate measurements for subsequent strain calculations between the first and second reference points 41 and 42.In some embodiments, the passive strain indicator 40 may comprise a positively applied square or rectangle wherein the first and second reference points 41 and 42 comprise two opposing sides of said square or rectangle.","In other embodiments, the passive strain indicator 40 may comprise at least two applied reference points 41 and 42 separated by a negative space 45 (i.e., an area in which the passive strain indicator material is not applied).","The negative space 45 may comprise, for example, an exposed portion of the exterior surface 11 of the turbine component 10.Alternatively or additionally, the negative space 45 may comprise a subsequently applied visually contrasting material that is distinct from the material of the at least two reference points 41 and 42 (or vice versa).","As illustrated in FIG.","2, in some embodiments, the passive strain indicator 40 may include a unique identifier 47 (hereinafter “UID”).","The UID 47 may comprise any type of barcode, label, tag, serial number, pattern or other identifying system that facilitates the identification of that particular passive strain indicator 40.In some embodiments, the UID 47 may additionally or alternatively comprise information about the turbine component 10 or the overall turbine that the passive strain indicator 40 is deposited on.","The UID 47 may thereby assist in the identification and tracking of particular passive strain indicators 40, turbine components 10 or even overall turbines to help correlate measurements for past, present and future operational tracking.","The passive strain indicator 40 may thereby be configured in one or more of a variety of locations of various turbine components 10.For example, as discussed above, the passive strain indicator 40 may be configured on a bucket, blade, vane, nozzle, shroud, rotor, transition piece or casing.","In such embodiments, the passive strain indicator 40 may be configured in one or more locations known to experience various forces during unit operation such as on or proximate airfoils, platforms, tips or any other suitable location.","Moreover, the passive strain indicator 40 may be deposited in one or more locations known to experience elevated temperatures.","For example the passive strain indicator 40 may be configured on a hot gas path or combustion turbine component 10.In some embodiments, multiple passive strain indicators 40 may be configured on a single turbine component 10 or on multiple turbine components 10.For example, a plurality of passive strain indicators 40 may be configured on a single turbine component 10 (e.g., a bucket) at various locations such that the strain may be determined at a greater number of locations about the individual turbine component 10.Alternatively or additionally, a plurality of like turbine components 10 (e.g., a plurality of buckets) may each have a passive strain indicator 40 configured in a standard location so that the amount of strain experienced by each specific turbine component 10 may be compared to other like turbine components 10.In even some embodiments, multiple different turbine components 10 of the same turbine unit (e.g., buckets and vanes for the same turbine) may each have a passive strain indicator 40 configured thereon so that the amount of strain experienced at different locations within the overall turbine may be determined.","Referring now to FIG.","3, a system 100 for monitoring turbine component 10 deformation is provided.","System 100 may include, for example, one or more passive strain indicators 40 which are configurable on the exterior surface 11 of one or more turbine components 10 as discussed above.","Further, system 100 may further include a data acquisition device 102 for analyzing one or more reference objects, such as passive strain indicators 40.Data acquisition devices 102 in accordance with the present disclosure may advantageously facilitate improved passive strain indicator 40 analysis.","In particular, such data acquisition devices 102 may advantageously provide low-distortion, high-contrast, small scale images which are particularly useful for turbine component 10 passive strain indicator 40 monitoring.","For example, in some embodiments, data acquisition devices 102 in accordance with the present disclosure can provide images having up to approximately 15 micron resolution, up to 0.001 millimeter overall accuracy, and/or measurement accuracy up to 5 microstrain or 0.000005 inch/inch.","To provide such images, and as discussed herein, data acquisition devices 102 in accordance with the present disclosure advantageously include a number of image optimization features, such as for example features for providing optimal light source standoff distances and light angles as well as features for providing optimal, consistent imaging angles relative to the reference object(s) being imaged, such as passive strain indicators 40.Referring now to FIGS.","3 through 7, embodiments of data acquisition devices 102 in accordance with the present disclosure are provided.","A device 102 in accordance with the present disclosure defines and extends along a longitudinal axis 104 between a front end 106 and a rear end 108.The front end 106 may generally be the end that contacts a surface, such as an external surface 11 of a turbine component 10, for imaging purposes.","As discussed herein, device 102 may be positioned such that the front end 106 is in contact with a surface such as an external surface 11, and further positioned such that a reference object such as a passive strain indicator 40 is within a viewing window 109 of the device 102.The viewing window 109 can generally be defined as the area visible to a lens assembly 110 of the device 102.Light may then be received and processed by an image capture device 120 to generate images, and these images may be analyzed as discussed herein.","Device 102 may thus include, for example, a lens assembly 110 and an image capture device 120.Lens assembly 110 may generally extend between a front end 112 and a rear end 114 along the longitudinal axis 104, and may magnify images viewed by the lens assembly 110 for processing by the image capture device 120.Lens assembly 110 in some embodiments may, for example, be a suitable camera lens, telescope lens, etc., and may include one or more lens spaced apart to provide the required magnification.","Notably, the required magnification for applications as discussed herein is not necessarily significantly large, and may for example, be approximately 0.5 to approximately 2 times magnification or more.","Image capture device 120 may generally be in communication with the lens assembly 110 for receiving and processing light from the lens assembly 110 to generate images.","In exemplary embodiments, for example, image capture device 120 may be a camera sensor which receives and processes light from a camera lens to generate images, such as digital images, as is generally understood.","Notably, the required resolution for applications as discussed herein is not necessarily significantly large, and may for example, be approximately 1.5 Megapixels or more.","Image capture device 120 may further be in communication with suitable hardware and/or software, via for example a suitable wired or wireless connection, for storing and analyzing the images from the image capture device 120 and device 102 generally.","Such hardware and/or software may, for example, generally analyze passive strain indicators 40 to determine whether deformation and strain have occurred as discussed above.","Device 102 can further, for example, include a light source 130.Light source may generally provide light to illuminate a reference object, such as a passive strain indicator 40, for imaging purposes.","Light source 130 is, in exemplary embodiments as shown, spaced from the front end 106 of the device 102.For example, light source 130 may be positioned proximate the front end 112 of the lens assembly 110, which may be spaced from the front end 106 of the device 102.Light source 130 may include, for example, one or more light emitting diodes (“LEDs”) or other light emitting components 132.The light emitting components 132 may, for example, be spaced apart in an annular array.","Light source 130 may further include a ring 134 on which the light emitting components 132 are mounted and positioned.","The light source 130 and light emitting components 132 thereof may generally be selectively activatable and, when activated, may provide light which provides illumination within the viewing window 109.Device 102 can further, for example, include a light tube 140 which is operable to transmit light from the light source 130 therethrough.","Light tube 140 extends along the longitudinal axis 104 between a front end 142 and a rear end 144, and is operable to transport light therethrough and emit the light from the front end 142.For example, in exemplary embodiments as shown, light tube 140 may be coupled at its rear end 144 to the light source 130, such that the light tube 140 and light source 130 are in contact.","The light emitting components 132, for example, may be positioned within recesses 145 defined in the rear end 144 of the light tube 140.When light is emitted from the light source 130, such as from the light emitting components 132 thereof, this light may travel through the light tube 140 and be emitted from the front end 142.Light tube 140 may, for example, be formed from a suitable plastic which allows light travel therethrough.","For example, in exemplary embodiments, light tube 140 may be formed from a translucent plastic, which may or may not be transparent.","In some embodiments, light tube 140 may be formed from a material that has a critical exposure of between approximately 10 mJ/cm2 and approximately 14 mJ/cm2 and/or an exposure that gives 0.010 inch thickness of between approximately 50 mJ/cm2 and approximately 60 mJ/cm2.As mentioned, light travels through the light tube 140 from the rear end 144 towards the front end 142, and is emitted from the front end 142.In some exemplary embodiments, an outer surface 146 of the light tube 140 may include one or more chamfered portions 147, which can assist in focusing and aiming the light as it travels through the light tube 140 for optimal output.","Each chamfered portion 147 of the outer surface 146 may taper towards an inner surface 148 (which defines an interior 149 of the light tube 140) along the longitudinal axis 104.For example, as shown, a chamfered portion 147 may be provided proximate the rear end 144 to initially focus the light after it enters the light tube 140.Additionally or alternatively, a chamfered portion 147 may be provided at the front of the light tube 140.This chamfered portion 147 may be proximate or may include the front end 142.In particular when this chamfered portion 147 includes the front end 142, this chamfered portion 147 may focus the light as it is emitted from the front end 142 for optimal light distribution within the viewing window 109.For example, in exemplary embodiments as shown, light may be emitted from the front end 142 at an angle of incidence 150 of between approximately 20 degrees and approximately 50 degrees, such as between approximately 30 degrees and approximately 45 degrees.","An angle of incidence within this range may provide optimal light distribution within the viewing window 109, particularly when viewing reference features on turbine components, and in exemplary embodiments may be due to the chamfered portion 147 that includes the front end 142.In exemplary embodiments as illustrated, light tube 140 is generally cylindrical, thus having a circular cross-sectional shape.","Alternatively, however, light tube 140 may have an oval, rectangular, triangular, or any other suitable polygonal cross-sectional shape.","Notably, light tube 140 also defines the viewing window 109.Specifically, the inner surface 148 and interior 149 define the viewing window 109.Images of a reference object, when the device 102 is in position on the surface on which the reference object is configured, are visible to the lens assembly 110 and received by the image capture device 120 through the interior 149, as illustrated.","Accordingly, front end 112 of lens assembly 110 may be positioned proximate rear end 144 of light tube 140.To prevent loss of light due to emission from the light tube 140 before the light reaches the front end 142, an outer shroud 160 and/or and inner shroud 162 may in exemplary embodiments be included in the data acquisition device 102.The shrouds 160, 162 may be positioned proximate and optionally in contact with the outer and inner surface 146, 148 of the light tube 140, respectively, and be formed form opaque materials which prevent light from travelling therethrough.","Accordingly, light that encounters the shrouds 160, 162 as it is travelling through the light tube 140 may be redirected within the light tube 140, rather than being allowed to escape.","For example, in exemplary embodiments one or both shrouds 160, 162 may be formed from a suitable metal, such as aluminum.","Outer shroud 160 may surround at least a portion of the outer surface 146 of the light tube 140, and inner shroud 162 may surround at least a portion of the inner surface 148 of the light tube 140.To further facilitate optimal lighting of the positioning of the viewing window 109, device 102 may further include one or more spacers 170 which are disposed proximate the front end 142 of the light tube 140.In exemplary embodiments, three spacers 170 are utilized, such that the device 102 can be optimally balanced on surfaces, such as exterior surfaces 11, that are both planer and surfaces that are non-planer.","However, it should be understood that any suitable number of spacers is within the scope and spirit of the present disclosure.","The spacers 170 are sized and positioned to provide optimal spacing between the light tube 140 and the exterior surface 11 when the device 102 is in an operative position in contact with a surface on which a reference object is configured, such that optimal lighting of the reference objected is provided and optimal images are received by the image capture device 120 from the lens assembly 110.For example, in exemplary embodiments, each spacer may be sized such that a distance 174 along the longitudinal axis 104 between a front end 172 of each of the plurality of spacers 170 and the front end 142 of the light tube 140 is between approximately 0.25 inches and approximately 0.75 inches, such as between approximately 0.4 inches and approximately 0.5 inches.","Thus, each spacer 170 may be sized to space the front end 142 of the light tube 140 from the exterior surface 11 of the turbine component 10 or other object by a distance 176 along the longitudinal axis 104 of between approximately 0.25 inches and approximately 0.75 inches, such as between approximately 0.4 inches and approximately 0.5 inches, when the device 102 is in an operative position in contact with the exterior surface 11 of the turbine component 10 or other object.","Device 102 may, in exemplary embodiments, further include an actuator 180.Actuator 180 may, for example, be a button, switch, or other suitable component which can be operated to activate other components of the device 102.For example, actuator 180 may be in communication (via a suitable wired or wireless connection) with the image capture device 120 and the light source 130.When the actuator 180 is actuated to activate the image capture device 120 and the light source 130, the light emitting components 132 may be activated to emit light and the image capture device 120 may be activated to receive one or more images.","These components may then be deactivated, either automatically or manually due to additional actuation of the actuator 180.Device 102 may additionally include a shell 190 which generally surrounds and contains various other components of the device 102.For example, shell 190 may surround the lens assembly 110, the image capture device 120, the light source 130, and the light tube 140.Shell 190 may further surround the actuator 180, which may be actuatable through the shell 190, or the actuator 180 may protrude through the shell 190.Notably, the front ends 172 of the spacers 170 may extend outwardly from the shell 190 along the longitudinal axis 104, to space the shell 190 from a surface when the device 102 is in an operative position as discussed.","It should be noted that, in exemplary embodiments, devices 102 as discussed herein are hand-held devices which may be manually operated for image analysis as discussed herein.","However, it should be understood that the present disclosure is not limited to hand-held devices.","Rather, any suitable devices, including for example automated devices and/or devices attached to, for example, robotic machines, etc., and which are manually operated or automated, are within the scope and spirit of the present disclosure.","Referring now to FIGS.","8 and 9, the present disclosure is further directed to methods 300 for analyzing reference objects, such as passive strain indicators 40.In exemplary embodiments, an image capture device 120 may be utilized to obtain images that are analyzed via a method 300 in accordance with the present disclosure.","However, it should be understood that the present disclosure is not limited image capture devices 120 and images captured therefrom, and rather that any suitable images of references objects may be analyzed in accordance with the present disclosure.","As mentioned, an image capture device 120 may be in communication with suitable hardware and/or software, via for example a suitable wired or wireless connection, for storing and analyzing the images from the image capture device 120 and device 102 generally.","Accordingly, an image capture device 120 may further include a processor 200 which may include such suitable hardware and/or software.","In exemplary embodiments, processor 200 may perform various of the steps of method 300 as discussed herein.","In general, as used herein, the term “processor” refers not only to integrated circuits referred to in the art as being included in a computer, but also refers to a controller, a microcontroller, a microcomputer, a programmable logic controller (PLC), an application specific integrated circuit, and other programmable circuits.","Processor 200 may also include various input/output channels for receiving inputs from and sending control signals to various other components with which the processor 200 is in communication, such as the lens assembly 110, light source 130, image capture device 200, etc.","Method 300 may include, for example, the step 310 of locating a reference object portion 314 (such as a passive strain indicator portion 314) relative to a background portion 316 within an image 312 of the reference object (such as the passive strain indicator 40) by performing a first analysis of the image 312.The first analysis is generally an analysis which differentiates the reference object portion 314 from the background portion 316 on the basis of differences in color depth.","First analysis may be performed on each individual pixel 318 or groups of pixels 319 defining the image 312.For example, in exemplary embodiments, a binary color depth analysis is performed on multi-pixel groups 319.For a binary analysis to occur, the number of bits-per-pixel of the image i.e.","128, 256, etc., is divided into two groups (generally a group which includes the lighter color depths and a group which includes the darker color depths).","Each group is categorized as a reference object portion 314 or a background portion 316.For example, the binary color depth analysis may categorize pixels or multi-pixel groups 319 that are darker color depths as denoting a reference object portion 314, and may categorize pixels or multi-pixel groups 319 that are lighter color depths as denoting a background portion 316.In alternative embodiments, first analysis need not be a binary analysis.","For example, first analysis may be a suitable greyscale analysis, as discussed herein, or other suitable comparison of color depths of the pixels 318 defining the image 312.Step 310 may generally locate the reference object portion 314 within the image 312.Further, in some embodiments, the information obtained from the first analysis may then be compared to predetermined threshold(s) for such information to determine if the threshold is satisfied.","A predetermined threshold may, for example, include one or more dimensions of the reference object, desired locations and orientation of the reference object portion 314 in the plane of the image 312, etc.","In some embodiments, if the predetermined threshold is satisfied, feedback signals may be provided to the device 102 to indicate such satisfaction.","For example, indicator lights 195 may be activated.","Method 300 may further include, for example, the step 320 of identifying reference object indicia (such as passive strain indicator indicia) of the reference object portion 314 by performing a second analysis of the image 312 (such as the entire image 312 or the reference object portion 314 thereof).","For passive strain indicators 40, passive strain indicator indicia may include, for example, reference points 41, 42, unique identifiers 47, and other identifiable components of the passive strain indicators 40.In general, reference object indicia are identifiable components of the reference object which provide some information about the reference object.","The second analysis is generally an analysis which further differentiates the reference object portion 314 from the background portion 316, and which differentiates the various reference object indicia, on the basis of differences in color depth.","Second analysis may be performed on each individual pixel 318 or groups of pixels 319 defining the image 312.For example, in exemplary embodiments, a binary color depth analysis is performed on single pixels 318.In alternative embodiments, second analysis need not be a binary analysis.","For example, second analysis may be a suitable greyscale analysis, as discussed herein, or other suitable comparison of color depths of the pixels 318 defining the image 312.Step 320 may generally further locate the reference object portion 314 within the image 312, and may further facilitate collection of information from the reference object of which the image 312 was taken.","For example, the existence of reference points 41, 42 may be confirmed, and identifying information for the reference object may be collected from the unique identifiers 47.Further, in some embodiments, the information obtained from the second analysis may then be compared to predetermined threshold(s) for such information to determine if the threshold is satisfied.","A predetermined threshold may, for example, include predetermined levels of indicia, such as reference points 41, 42, which can be confirmed.","Method 300 may further include, for example, the step 330 of conducting a quality analysis of the reference object portion 314 by performing a third analysis of the image 312 (such as the entire image 312 or the reference object portion 314 thereof).","The third analysis is generally an analysis which further differentiates the reference object portion 314 from the background portion 316, and which further differentiates the various reference object indicia, on the basis of differences in color depth.","In exemplary embodiments, third analysis utilizes a higher bit-depth than the first analysis.","Further, in some embodiments, third analysis may utilize a higher bit-depth than the second analysis.","Third analysis may be performed on each individual pixel 318, or on sub-sections of individual pixels.","For example, pixels 318 may be divided into 100 sub-sections, 1000 sub-sections, 10,000 sub-sections, or any other suitable number of subsections, and the third analysis may be performed on each individual sub-section.","In exemplary embodiments, a greyscale analysis is performed on the bits-per-pixel of the image i.e.","128, 256, etc.","For example, in some embodiments, a 256 bit-per-pixel greyscale analysis is performed.","Accordingly, each pixel 318 or sub-section thereof is categorized as having a particular color depth per the 128, 256, etc.","color depth scale.","Step 330 may generally allow for the strength of the image 312 to be analyzed by, for example, analyzing the contrast between neighboring pixels 318 or sub-sections thereof.","For example, it is generally desirable for the contrast between pixels at the border of features of the reference object portion 314, such as the edges of the reference object portion 314 or indicia thereof, to be high, thus indicating the distinction between the reference object portion 314 or indicia thereof and the background portion 316, etc.","Further, step 330 may generally allow for the sharpness of the image 312 to be analyzed by, for example, analyzing the width in pixels 318 or sub-sections thereof of various features of the reference object portion 314.For example, it is generally desirable for the width of features of the reference object portion 314, such as the edges of the reference object portion 314 or indicia thereof, to be low, thus indicating the sharpness of the image of the reference object portion 314 or indicia thereof relative to the background portion 316, etc.","Further, in some embodiment, the information obtained from the third analysis may then be compared to predetermined threshold(s) for such information to determine if the threshold is satisfied.","A predetermined threshold may, for example, include predetermined strength and sharpness levels.","Steps 310, 320 and/or 330 may generally be utilized to determine whether an image 312 is of sufficient quality to be saved for subsequent analysis, such as subsequent strain analysis as discussed herein.","For example, as discussed, in some embodiments, the information obtained from the color analyses in each step 310, 320, 330 may compared to various predetermined thresholds.","In exemplary embodiments, method 300 may further include the step 340 of saving the image 312 when the locating step 310, the identifying step 320 and/or the conducting step 330 each satisfy the required predetermined threshold(s).","Such image 312 may then be utilized in subsequent analysis of the reference object.","In some embodiments, method 300 may further include the step 350 of comparing the saved image 312 to one or more previously-saved images 312.The previously-saved images 312 are generally images 312 that have been saved within the same iteration of reference object analysis, i.e.","during the same operation of the device 102 and processor 200 to obtain images during a particular time period.","In general, differences between the reference object portions 314, such as differences between the indicia thereof, may be analyzed.","Optimally, little or no differences should be present, because the images are taken during a single iteration.","In general, a threshold may be set for particular differences, such as a threshold strain.","For example, a threshold strain may be 5 microstrain, 10 microstrain, 20 microstrain, etc.","If a difference exceeds the threshold, this may indicate that outside forces are influencing the accuracy of the images, thus allowing a user to cease analysis and perform a quality check of the associated system 100, device 102, processor 200, etc.","It should be noted that steps 310, 320 and/or 330 as discussed herein may in exemplary embodiments, be performed in real time as images are received by the processor 200 from image captures device 120.Method 300 may further include various steps for initially operating a device, such as device 102, to analyze a reference object.","For example, method 300 may include the step 360 of activating a light source, such as light source 130.Light source 130 may be activated (such as by processor 200) either automatically within an automated system or manually in response to an input by a user, such by a user pressing actuator 180.Further, method 300 may include the step 370 of activating the processor 200 to analyze images.","In accordance with this step, the processor 200 may enter a mode wherein steps 310, 320 and/or 330 are performed.","Such activation may occur (such as by processor 200) either automatically within an automated system or manually in response to an input by a user, such by a user pressing actuator 180.Further, method 300 may include the step 380 of contacting the exterior surface on which the reference object is configured, such as the exterior surface 11 of the turbine component 10, with a device such as device 102.In exemplary embodiments as discussed herein, spacers 170 may contact the exterior surface 11.Such contact may occur either automatically within an automated system (such as by processor 200) or manually by a user.","Notably, in exemplary embodiments, step 370 may occur after step 360.Steps 310-350 may occur after such steps.","This written description uses examples to disclose the invention, including the best mode, and also to enable any person skilled in the art to practice the invention, including making and using any devices or systems and performing any incorporated methods.","The patentable scope of the invention is defined by the claims, and may include other examples that occur to those skilled in the art.","Such other examples are intended to be within the scope of the claims if they include structural elements that do not differ from the literal language of the claims, or if they include equivalent structural elements with insubstantial differences from the literal languages of the claims."]],"string":"[\n [\n \"DATA ACQUISITION DEVICES, SYSTEMS AND METHOD FOR ANALYZING PASSIVE STRAIN INDICATORS AND MONITORING TURBINE COMPONENT STRAIN\",\n \"Data acquisition devices for analyzing reference objects and systems for monitoring turbine component deformation are provided.\",\n \"A data acquisition device has a longitudinal axis and includes a lens assembly and an image capture device in communication with the lens assembly for receiving and processing light from the lens assembly to generate images.\",\n \"The data acquisition device further includes a light source and a light tube coupled at a rear end to the light source.\",\n \"The light tube extends along the longitudinal axis between a front end and the rear end, and is operable to transport light from the light source therethrough and emit the light from the front end.\",\n \"The data acquisition device further includes an actuator operable to activate the image capture device and the light source.\"\n ],\n [\n \"1.A system for monitoring turbine component deformation, the turbine component having an exterior surface, the system comprising: a passive strain indicator configurable on the exterior surface of the turbine component; and a data acquisition device for analyzing the passive strain indicator, the data acquisition device comprising: a lens assembly; an image capture device in communication with the lens assembly for receiving and processing light from the lens assembly to generate images; a light source; a light tube coupled at a rear end to the light source and extending along a longitudinal axis between a front end and the rear end, the light tube operable to transport light from the light source therethrough and emit the light from the front end; an actuator operable to activate the image capture device and the light source; a shell, the shell surrounding the lens assembly, the image capture device, the light source, and the light tube; and a plurality of spacers disposed proximate the front end of the light tube, each of the plurality of spacers extending from the shell and sized to space the front end of the light tube from the exterior surface of the turbine component when the data acquisition device is in an operative position in contact with the exterior surface of the turbine component.\",\n \"2.The system of claim 1, wherein the data acquisition device further comprises an outer shroud surrounding at least a portion of an outer surface of the light tube.\",\n \"3.The system of claim 1, wherein an outer surface of the light tube comprises a chamfered portion, the chamfered portion tapering towards an inner surface of the light tube along the longitudinal axis.\",\n \"4.The system of claim 3, wherein the chamfered portion includes the front end.\",\n \"5.The system of claim 1, wherein light is emitted from the front end of the light tube at an angle of incidence of between approximately 20 degrees and approximately 50 degrees.\",\n \"6.The system of claim 1, wherein each of the plurality of spacers is sized to space the front end of the light tube from the exterior surface of the turbine component by a distance along the longitudinal axis of between approximately 0.25 inches and approximately 0.75 inches when the data acquisition device is in an operative position in contact with the exterior surface of the turbine component.\",\n \"7.The system of claim 1, wherein the data acquisition device further comprises a processor, the processor configured for: locating a passive strain indicator portion relative to a background portion within an image of the passive strain indicator by performing a first analysis of the image; identifying passive strain indicator indicia of the passive strain indicator portion by performing a second analysis of the image; and conducting a quality analysis of the passive strain indicator portion by performing a third analysis of the passive strain indicator portion of the image, the third analysis utilizing a higher bit-depth than the first analysis.\",\n \"8.A method for analyzing a passive strain indicator, the method comprising: locating a passive strain indicator portion relative to a background portion within an image of the passive strain indicator by performing a first analysis of the image; identifying passive strain indicator indicia of the passive strain indicator portion by performing a second analysis of the image; and conducting a quality analysis of the passive strain indicator portion by performing a third analysis of the passive strain indicator portion of the image, the third analysis utilizing a higher bit-depth than the first analysis.\",\n \"9.The method of claim 16, wherein the first analysis is a binary analysis of multi-pixel groups of the passive strain indicator portion of the image.\",\n \"10.The method of claim 16, wherein the second analysis is a binary analysis of single pixels of the passive strain indicator portion of the image.\",\n \"11.The method of claim 16, wherein the third analysis is a 256 bit-per-pixel greyscale analysis.\",\n \"12.The method of claim 16, further comprising the step of activating a light source.\",\n \"13.The method of claim 16, further comprising the step of saving the image when the locating step, the identifying step, and the conducting step each satisfy a predetermined threshold.\",\n \"14.The method of claim 21, further comprising comparing the image to a previously-saved image.\"\n ],\n [\n \" BACKGROUND OF THE INVENTION Turbomachines are widely utilized in fields such as power generation and aircraft engines.\",\n \"For example, a conventional gas turbine system includes a compressor section, a combustor section, and at least one turbine section.\",\n \"The compressor section is configured to compress air as the air flows through the compressor section.\",\n \"The air is then flowed from the compressor section to the combustor section, where it is mixed with fuel and combusted, generating a hot gas flow.\",\n \"The hot gas flow is provided to the turbine section, which utilizes the hot gas flow by extracting energy from it to power the compressor, an electrical generator, and other various loads.\",\n \"During operation of a turbomachine, various components (collectively known as turbine components) within the turbomachine and particularly within the turbine section of the turbomachine, such as turbine blades, may be subject to creep due to high temperatures and stresses.\",\n \"For turbine blades, creep may cause portions of or the entire blade to elongate so that the blade tips contact a stationary structure, for example a turbine casing, and potentially cause unwanted vibrations and/or reduced performance during operation.\",\n \"Accordingly, it is desirable to monitor turbine components for creep.\",\n \"One approach to monitoring turbine components for creep is to configure passive strain indicators on the components, and analyze the passive strain indicators at various intervals to monitor for deformations associated with creep strain.\",\n \"However, such deformation can in many cases be on the order of 0.01% of an original dimension, thus requiring specialized equipment for strain monitoring.\",\n \"Presently known acquisition tools and techniques for monitoring such passive strain indicators may in some cases not provide the desired sufficiently low-distortion, high-contrast, small scale images for these applications.\",\n \"Accordingly, alternative systems and methods for monitoring turbine component strain are desired in the art.\",\n \"Further, alternative data acquisition devices and methods for analyzing reference objects, such as passive strain indicators, are desired in the art.\",\n \"Systems, devices and methods which provide sufficiently low-distortion, high-contrast, small scale images for turbine component passive strain indicator monitoring would be particularly advantageous.\"\n ],\n [\n \" BRIEF DESCRIPTION OF THE INVENTION Aspects and advantages of the invention will be set forth in part in the following description, or may be obvious from the description, or may be learned through practice of the invention.\",\n \"In accordance with one embodiment of the present disclosure, a data acquisition device for analyzing a reference object is provided.\",\n \"The data acquisition device has a longitudinal axis and includes a lens assembly and an image capture device in communication with the lens assembly for receiving and processing light from the lens assembly to generate images.\",\n \"The data acquisition device further includes a light source and a light tube coupled at a rear end to the light source.\",\n \"The light tube extends along the longitudinal axis between a front end and the rear end, and is operable to transport light from the light source therethrough and emit the light from the front end.\",\n \"The data acquisition device further includes an actuator operable to activate the image capture device and the light source.\",\n \"In accordance with another embodiment of the present disclosure, a system for monitoring turbine component deformation is provided.\",\n \"The turbine component has an exterior surface.\",\n \"The system includes a passive strain indicator configurable on the exterior surface of the turbine component, and a data acquisition device for analyzing the passive strain indicator.\",\n \"The data acquisition device includes a lens assembly and an image capture device in communication with the lens assembly for receiving and processing light from the lens assembly to generate images.\",\n \"The data acquisition device further includes a light source, and a light tube coupled at a rear end to the light source.\",\n \"The light tube extends along a longitudinal axis between a front end and the rear end, and is operable to transport light from the light source therethrough and emit the light from the front end.\",\n \"The data acquisition device further includes an actuator operable to activate the image capture device and the light source, and a shell, the shell surrounding the lens assembly, the image capture device, the light source, and the light tube.\",\n \"The data acquisition device further includes a plurality of spacers disposed proximate the front end of the light tube.\",\n \"Each of the plurality of spacers extends from the shell and is sized to space the front end of the light tube from the exterior surface of the turbine component when the data acquisition device is in an operative position in contact with the exterior surface of the turbine component.\",\n \"In accordance with another embodiment of the present disclosure, a method for analyzing a passive strain indicator is provided.\",\n \"The method includes locating a passive strain indicator portion relative to a background portion within an image of the passive strain indicator by performing a first analysis of the image.\",\n \"The method further includes identifying passive strain indicator indicia of the passive strain indicator portion by performing a second analysis of the image.\",\n \"The method further includes conducting a quality analysis of the passive strain indicator portion by performing a third analysis of the passive strain indicator portion of the image, the third analysis utilizing a higher bit-depth than the first analysis.\",\n \"These and other features, aspects and advantages of the present invention will become better understood with reference to the following description and appended claims.\",\n \"The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and, together with the description, serve to explain the principles of the invention.\"\n ],\n [\n \"CROSS-REFERENCE TO RELATED PATENT APPLICATIONS This application is a continuation-in-part of application Ser.\",\n \"No.\",\n \"15/384,513 filed Dec. 20, 2016 and titled “Data Acquisition Devices, Systems and Method for Analyzing Passing Strain Indicators and Monitoring Turbine Component Strain”, which is incorporated by reference herein.\",\n \"FIELD OF THE INVENTION The present disclosure relates generally to data acquisition devices and methods for analyzing reference objects such as passive strain indicators, and to systems for monitoring turbine component strain which utilize such devices to analyze passive strain indicators.\",\n \"BACKGROUND OF THE INVENTION Turbomachines are widely utilized in fields such as power generation and aircraft engines.\",\n \"For example, a conventional gas turbine system includes a compressor section, a combustor section, and at least one turbine section.\",\n \"The compressor section is configured to compress air as the air flows through the compressor section.\",\n \"The air is then flowed from the compressor section to the combustor section, where it is mixed with fuel and combusted, generating a hot gas flow.\",\n \"The hot gas flow is provided to the turbine section, which utilizes the hot gas flow by extracting energy from it to power the compressor, an electrical generator, and other various loads.\",\n \"During operation of a turbomachine, various components (collectively known as turbine components) within the turbomachine and particularly within the turbine section of the turbomachine, such as turbine blades, may be subject to creep due to high temperatures and stresses.\",\n \"For turbine blades, creep may cause portions of or the entire blade to elongate so that the blade tips contact a stationary structure, for example a turbine casing, and potentially cause unwanted vibrations and/or reduced performance during operation.\",\n \"Accordingly, it is desirable to monitor turbine components for creep.\",\n \"One approach to monitoring turbine components for creep is to configure passive strain indicators on the components, and analyze the passive strain indicators at various intervals to monitor for deformations associated with creep strain.\",\n \"However, such deformation can in many cases be on the order of 0.01% of an original dimension, thus requiring specialized equipment for strain monitoring.\",\n \"Presently known acquisition tools and techniques for monitoring such passive strain indicators may in some cases not provide the desired sufficiently low-distortion, high-contrast, small scale images for these applications.\",\n \"Accordingly, alternative systems and methods for monitoring turbine component strain are desired in the art.\",\n \"Further, alternative data acquisition devices and methods for analyzing reference objects, such as passive strain indicators, are desired in the art.\",\n \"Systems, devices and methods which provide sufficiently low-distortion, high-contrast, small scale images for turbine component passive strain indicator monitoring would be particularly advantageous.\",\n \"BRIEF DESCRIPTION OF THE INVENTION Aspects and advantages of the invention will be set forth in part in the following description, or may be obvious from the description, or may be learned through practice of the invention.\",\n \"In accordance with one embodiment of the present disclosure, a data acquisition device for analyzing a reference object is provided.\",\n \"The data acquisition device has a longitudinal axis and includes a lens assembly and an image capture device in communication with the lens assembly for receiving and processing light from the lens assembly to generate images.\",\n \"The data acquisition device further includes a light source and a light tube coupled at a rear end to the light source.\",\n \"The light tube extends along the longitudinal axis between a front end and the rear end, and is operable to transport light from the light source therethrough and emit the light from the front end.\",\n \"The data acquisition device further includes an actuator operable to activate the image capture device and the light source.\",\n \"In accordance with another embodiment of the present disclosure, a system for monitoring turbine component deformation is provided.\",\n \"The turbine component has an exterior surface.\",\n \"The system includes a passive strain indicator configurable on the exterior surface of the turbine component, and a data acquisition device for analyzing the passive strain indicator.\",\n \"The data acquisition device includes a lens assembly and an image capture device in communication with the lens assembly for receiving and processing light from the lens assembly to generate images.\",\n \"The data acquisition device further includes a light source, and a light tube coupled at a rear end to the light source.\",\n \"The light tube extends along a longitudinal axis between a front end and the rear end, and is operable to transport light from the light source therethrough and emit the light from the front end.\",\n \"The data acquisition device further includes an actuator operable to activate the image capture device and the light source, and a shell, the shell surrounding the lens assembly, the image capture device, the light source, and the light tube.\",\n \"The data acquisition device further includes a plurality of spacers disposed proximate the front end of the light tube.\",\n \"Each of the plurality of spacers extends from the shell and is sized to space the front end of the light tube from the exterior surface of the turbine component when the data acquisition device is in an operative position in contact with the exterior surface of the turbine component.\",\n \"In accordance with another embodiment of the present disclosure, a method for analyzing a passive strain indicator is provided.\",\n \"The method includes locating a passive strain indicator portion relative to a background portion within an image of the passive strain indicator by performing a first analysis of the image.\",\n \"The method further includes identifying passive strain indicator indicia of the passive strain indicator portion by performing a second analysis of the image.\",\n \"The method further includes conducting a quality analysis of the passive strain indicator portion by performing a third analysis of the passive strain indicator portion of the image, the third analysis utilizing a higher bit-depth than the first analysis.\",\n \"These and other features, aspects and advantages of the present invention will become better understood with reference to the following description and appended claims.\",\n \"The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and, together with the description, serve to explain the principles of the invention.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS A full and enabling disclosure of the present invention, including the best mode thereof, directed to one of ordinary skill in the art, is set forth in the specification, which makes reference to the appended figures, in which: FIG.\",\n \"1 is a perspective view of an exemplary turbine component comprising a passive strain indicator in accordance with one embodiment of the present disclosure; FIG.\",\n \"2 is a top view of an exemplary passive strain indicator in accordance with one embodiment of the present disclosure; FIG.\",\n \"3 is a side view of a system for monitoring turbine component strain in accordance with one embodiment of the present disclosure; FIG.\",\n \"4 is a perspective view of a data acquisition device in accordance with one embodiment of the present disclosure; FIG.\",\n \"5 is a perspective cross-sectional view of a data acquisition device in accordance with one embodiment of the present disclosure; FIG.\",\n \"6 is a side view of a data acquisition device, with various components shown in shadow for illustrative purposes, in accordance with one embodiment of the present disclosure; FIG.\",\n \"7 is a perspective view of a light tube of a data acquisition device in accordance with one embodiment of the present disclosure; FIG.\",\n \"8 illustrates an image of a passive strain indicator in accordance with one embodiment of the present disclosure; and FIG.\",\n \"9 is a flow chart illustrating a method in accordance with one embodiment of the present disclosure.\",\n \"DETAILED DESCRIPTION OF THE INVENTION Reference now will be made in detail to embodiments of the invention, one or more examples of which are illustrated in the drawings.\",\n \"Each example is provided by way of explanation of the invention, not limitation of the invention.\",\n \"In fact, it will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the scope or spirit of the invention.\",\n \"For instance, features illustrated or described as part of one embodiment can be used with another embodiment to yield a still further embodiment.\",\n \"Thus, it is intended that the present invention covers such modifications and variations as come within the scope of the appended claims and their equivalents.\",\n \"Referring now to FIG.\",\n \"1, a turbine component 10 is illustrated with a passive strain indicator 40 configured on a portion of the turbine component's exterior surface 11.The turbine component 10 can comprise a variety of specific components such as those utilized in high temperature applications (e.g., components comprising nickel or cobalt based superalloys).\",\n \"For example, in some embodiments, the turbine component 10 may comprise a combustion component or hot gas path component.\",\n \"In some particular embodiments, the turbine component 10 may comprise a bucket, blade, vane, nozzle, shroud, rotor, transition piece or casing.\",\n \"In other embodiments, the turbine component 10 may comprise any other component of a turbine such as a component for a gas turbine, industrial gas turbine, steam turbine or the like.\",\n \"The turbine component 10 has an exterior surface 11 on which passive strain indicators 40 are configured.\",\n \"Passive strain indicators 40 in accordance with the present disclosure may be configured on the exterior surface 11 using any suitable techniques, including deposition techniques; other suitable additive manufacturing techniques; subtractive techniques such as laser ablation, engraving, machining, etc.\",\n \"; appearance- change techniques such as annealing, direct surface discoloration, or techniques to cause local changes in reflectivity; mounting of previously formed passive strain indicators 40 using suitable mounting apparatus or techniques such as adhering, welding, brazing, etc.\",\n \"; or identifying pre-existing characteristics of the exterior surface 11 that can function as the components of a passive strain indicator 40.Referring now to FIGS.\",\n \"1 and 2, a passive strain indicator 40 is configured on a portion of the exterior surface 11 of the turbine component 10.The passive strain indicator 40 generally comprises at least two reference points 41 and 42 that can be used to measure a distance D between said at least two reference points 41 and 42 at a plurality of time intervals.\",\n \"As should be appreciated to those skilled in the art, these measurements can help determine the amount of strain, strain rate, creep, fatigue, stress, etc.\",\n \"at that region of the turbine component 10.The at least two reference points 41 and 42 can be disposed at a variety of distances and in a variety of locations depending on the specific turbine component 10 so long as the distance D there between can be measured.\",\n \"Moreover, the at least two reference points 41 and 42 may comprise dots, lines, circles, boxes or any other geometrical or non-geometrical shape so long as they are consistently identifiable and may be used to measure the distance D there between.\",\n \"The passive strain indicator 40 may comprise a variety of different configurations and cross-sections such as by incorporating a variety of differently shaped, sized, and positioned reference points 41 and 42.For example, as illustrated in FIG.\",\n \"2, the passive strain indicator 40 may comprise a variety of different reference points comprising various shapes and sizes.\",\n \"Such embodiments may provide for a greater variety of distance measurements D such as between the outer most reference points (as illustrated), between two internal or external reference points, or any combination there between.\",\n \"The greater variety may further provide a more robust strain analysis on a particular portion of the turbine component 10 by providing strain measurements across a greater variety of locations.\",\n \"Furthermore, the dimensions of the passive strain indicator 40 may depend on, for example, the turbine component 10, the location of the passive strain indicator 40, the targeted precision of the measurement, application technique, and optical measurement technique.\",\n \"For example, in some embodiments, the passive strain indicator 40 may comprise a length and width ranging from less than 1 millimeter to greater than 300 millimeters.\",\n \"Moreover, the passive strain indicator 40 may comprise any thickness that is suitable for application and subsequent optical identification without significantly impacting the performance of the underlying turbine component 10.Notably, this thickness may be a positive thickness away from the surface 11 (such as when additive techniques are utilized) or a negative thickness into the surface 11 (such as when subtractive techniques are utilized).\",\n \"For example, in some embodiments, the passive strain indicator 40 may comprise a thickness of less than from about 0.01 millimeters to greater than 1 millimeter.\",\n \"In some embodiments, the passive strain indicator 40 may have a substantially uniform thickness.\",\n \"Such embodiments may help facilitate more accurate measurements for subsequent strain calculations between the first and second reference points 41 and 42.In some embodiments, the passive strain indicator 40 may comprise a positively applied square or rectangle wherein the first and second reference points 41 and 42 comprise two opposing sides of said square or rectangle.\",\n \"In other embodiments, the passive strain indicator 40 may comprise at least two applied reference points 41 and 42 separated by a negative space 45 (i.e., an area in which the passive strain indicator material is not applied).\",\n \"The negative space 45 may comprise, for example, an exposed portion of the exterior surface 11 of the turbine component 10.Alternatively or additionally, the negative space 45 may comprise a subsequently applied visually contrasting material that is distinct from the material of the at least two reference points 41 and 42 (or vice versa).\",\n \"As illustrated in FIG.\",\n \"2, in some embodiments, the passive strain indicator 40 may include a unique identifier 47 (hereinafter “UID”).\",\n \"The UID 47 may comprise any type of barcode, label, tag, serial number, pattern or other identifying system that facilitates the identification of that particular passive strain indicator 40.In some embodiments, the UID 47 may additionally or alternatively comprise information about the turbine component 10 or the overall turbine that the passive strain indicator 40 is deposited on.\",\n \"The UID 47 may thereby assist in the identification and tracking of particular passive strain indicators 40, turbine components 10 or even overall turbines to help correlate measurements for past, present and future operational tracking.\",\n \"The passive strain indicator 40 may thereby be configured in one or more of a variety of locations of various turbine components 10.For example, as discussed above, the passive strain indicator 40 may be configured on a bucket, blade, vane, nozzle, shroud, rotor, transition piece or casing.\",\n \"In such embodiments, the passive strain indicator 40 may be configured in one or more locations known to experience various forces during unit operation such as on or proximate airfoils, platforms, tips or any other suitable location.\",\n \"Moreover, the passive strain indicator 40 may be deposited in one or more locations known to experience elevated temperatures.\",\n \"For example the passive strain indicator 40 may be configured on a hot gas path or combustion turbine component 10.In some embodiments, multiple passive strain indicators 40 may be configured on a single turbine component 10 or on multiple turbine components 10.For example, a plurality of passive strain indicators 40 may be configured on a single turbine component 10 (e.g., a bucket) at various locations such that the strain may be determined at a greater number of locations about the individual turbine component 10.Alternatively or additionally, a plurality of like turbine components 10 (e.g., a plurality of buckets) may each have a passive strain indicator 40 configured in a standard location so that the amount of strain experienced by each specific turbine component 10 may be compared to other like turbine components 10.In even some embodiments, multiple different turbine components 10 of the same turbine unit (e.g., buckets and vanes for the same turbine) may each have a passive strain indicator 40 configured thereon so that the amount of strain experienced at different locations within the overall turbine may be determined.\",\n \"Referring now to FIG.\",\n \"3, a system 100 for monitoring turbine component 10 deformation is provided.\",\n \"System 100 may include, for example, one or more passive strain indicators 40 which are configurable on the exterior surface 11 of one or more turbine components 10 as discussed above.\",\n \"Further, system 100 may further include a data acquisition device 102 for analyzing one or more reference objects, such as passive strain indicators 40.Data acquisition devices 102 in accordance with the present disclosure may advantageously facilitate improved passive strain indicator 40 analysis.\",\n \"In particular, such data acquisition devices 102 may advantageously provide low-distortion, high-contrast, small scale images which are particularly useful for turbine component 10 passive strain indicator 40 monitoring.\",\n \"For example, in some embodiments, data acquisition devices 102 in accordance with the present disclosure can provide images having up to approximately 15 micron resolution, up to 0.001 millimeter overall accuracy, and/or measurement accuracy up to 5 microstrain or 0.000005 inch/inch.\",\n \"To provide such images, and as discussed herein, data acquisition devices 102 in accordance with the present disclosure advantageously include a number of image optimization features, such as for example features for providing optimal light source standoff distances and light angles as well as features for providing optimal, consistent imaging angles relative to the reference object(s) being imaged, such as passive strain indicators 40.Referring now to FIGS.\",\n \"3 through 7, embodiments of data acquisition devices 102 in accordance with the present disclosure are provided.\",\n \"A device 102 in accordance with the present disclosure defines and extends along a longitudinal axis 104 between a front end 106 and a rear end 108.The front end 106 may generally be the end that contacts a surface, such as an external surface 11 of a turbine component 10, for imaging purposes.\",\n \"As discussed herein, device 102 may be positioned such that the front end 106 is in contact with a surface such as an external surface 11, and further positioned such that a reference object such as a passive strain indicator 40 is within a viewing window 109 of the device 102.The viewing window 109 can generally be defined as the area visible to a lens assembly 110 of the device 102.Light may then be received and processed by an image capture device 120 to generate images, and these images may be analyzed as discussed herein.\",\n \"Device 102 may thus include, for example, a lens assembly 110 and an image capture device 120.Lens assembly 110 may generally extend between a front end 112 and a rear end 114 along the longitudinal axis 104, and may magnify images viewed by the lens assembly 110 for processing by the image capture device 120.Lens assembly 110 in some embodiments may, for example, be a suitable camera lens, telescope lens, etc., and may include one or more lens spaced apart to provide the required magnification.\",\n \"Notably, the required magnification for applications as discussed herein is not necessarily significantly large, and may for example, be approximately 0.5 to approximately 2 times magnification or more.\",\n \"Image capture device 120 may generally be in communication with the lens assembly 110 for receiving and processing light from the lens assembly 110 to generate images.\",\n \"In exemplary embodiments, for example, image capture device 120 may be a camera sensor which receives and processes light from a camera lens to generate images, such as digital images, as is generally understood.\",\n \"Notably, the required resolution for applications as discussed herein is not necessarily significantly large, and may for example, be approximately 1.5 Megapixels or more.\",\n \"Image capture device 120 may further be in communication with suitable hardware and/or software, via for example a suitable wired or wireless connection, for storing and analyzing the images from the image capture device 120 and device 102 generally.\",\n \"Such hardware and/or software may, for example, generally analyze passive strain indicators 40 to determine whether deformation and strain have occurred as discussed above.\",\n \"Device 102 can further, for example, include a light source 130.Light source may generally provide light to illuminate a reference object, such as a passive strain indicator 40, for imaging purposes.\",\n \"Light source 130 is, in exemplary embodiments as shown, spaced from the front end 106 of the device 102.For example, light source 130 may be positioned proximate the front end 112 of the lens assembly 110, which may be spaced from the front end 106 of the device 102.Light source 130 may include, for example, one or more light emitting diodes (“LEDs”) or other light emitting components 132.The light emitting components 132 may, for example, be spaced apart in an annular array.\",\n \"Light source 130 may further include a ring 134 on which the light emitting components 132 are mounted and positioned.\",\n \"The light source 130 and light emitting components 132 thereof may generally be selectively activatable and, when activated, may provide light which provides illumination within the viewing window 109.Device 102 can further, for example, include a light tube 140 which is operable to transmit light from the light source 130 therethrough.\",\n \"Light tube 140 extends along the longitudinal axis 104 between a front end 142 and a rear end 144, and is operable to transport light therethrough and emit the light from the front end 142.For example, in exemplary embodiments as shown, light tube 140 may be coupled at its rear end 144 to the light source 130, such that the light tube 140 and light source 130 are in contact.\",\n \"The light emitting components 132, for example, may be positioned within recesses 145 defined in the rear end 144 of the light tube 140.When light is emitted from the light source 130, such as from the light emitting components 132 thereof, this light may travel through the light tube 140 and be emitted from the front end 142.Light tube 140 may, for example, be formed from a suitable plastic which allows light travel therethrough.\",\n \"For example, in exemplary embodiments, light tube 140 may be formed from a translucent plastic, which may or may not be transparent.\",\n \"In some embodiments, light tube 140 may be formed from a material that has a critical exposure of between approximately 10 mJ/cm2 and approximately 14 mJ/cm2 and/or an exposure that gives 0.010 inch thickness of between approximately 50 mJ/cm2 and approximately 60 mJ/cm2.As mentioned, light travels through the light tube 140 from the rear end 144 towards the front end 142, and is emitted from the front end 142.In some exemplary embodiments, an outer surface 146 of the light tube 140 may include one or more chamfered portions 147, which can assist in focusing and aiming the light as it travels through the light tube 140 for optimal output.\",\n \"Each chamfered portion 147 of the outer surface 146 may taper towards an inner surface 148 (which defines an interior 149 of the light tube 140) along the longitudinal axis 104.For example, as shown, a chamfered portion 147 may be provided proximate the rear end 144 to initially focus the light after it enters the light tube 140.Additionally or alternatively, a chamfered portion 147 may be provided at the front of the light tube 140.This chamfered portion 147 may be proximate or may include the front end 142.In particular when this chamfered portion 147 includes the front end 142, this chamfered portion 147 may focus the light as it is emitted from the front end 142 for optimal light distribution within the viewing window 109.For example, in exemplary embodiments as shown, light may be emitted from the front end 142 at an angle of incidence 150 of between approximately 20 degrees and approximately 50 degrees, such as between approximately 30 degrees and approximately 45 degrees.\",\n \"An angle of incidence within this range may provide optimal light distribution within the viewing window 109, particularly when viewing reference features on turbine components, and in exemplary embodiments may be due to the chamfered portion 147 that includes the front end 142.In exemplary embodiments as illustrated, light tube 140 is generally cylindrical, thus having a circular cross-sectional shape.\",\n \"Alternatively, however, light tube 140 may have an oval, rectangular, triangular, or any other suitable polygonal cross-sectional shape.\",\n \"Notably, light tube 140 also defines the viewing window 109.Specifically, the inner surface 148 and interior 149 define the viewing window 109.Images of a reference object, when the device 102 is in position on the surface on which the reference object is configured, are visible to the lens assembly 110 and received by the image capture device 120 through the interior 149, as illustrated.\",\n \"Accordingly, front end 112 of lens assembly 110 may be positioned proximate rear end 144 of light tube 140.To prevent loss of light due to emission from the light tube 140 before the light reaches the front end 142, an outer shroud 160 and/or and inner shroud 162 may in exemplary embodiments be included in the data acquisition device 102.The shrouds 160, 162 may be positioned proximate and optionally in contact with the outer and inner surface 146, 148 of the light tube 140, respectively, and be formed form opaque materials which prevent light from travelling therethrough.\",\n \"Accordingly, light that encounters the shrouds 160, 162 as it is travelling through the light tube 140 may be redirected within the light tube 140, rather than being allowed to escape.\",\n \"For example, in exemplary embodiments one or both shrouds 160, 162 may be formed from a suitable metal, such as aluminum.\",\n \"Outer shroud 160 may surround at least a portion of the outer surface 146 of the light tube 140, and inner shroud 162 may surround at least a portion of the inner surface 148 of the light tube 140.To further facilitate optimal lighting of the positioning of the viewing window 109, device 102 may further include one or more spacers 170 which are disposed proximate the front end 142 of the light tube 140.In exemplary embodiments, three spacers 170 are utilized, such that the device 102 can be optimally balanced on surfaces, such as exterior surfaces 11, that are both planer and surfaces that are non-planer.\",\n \"However, it should be understood that any suitable number of spacers is within the scope and spirit of the present disclosure.\",\n \"The spacers 170 are sized and positioned to provide optimal spacing between the light tube 140 and the exterior surface 11 when the device 102 is in an operative position in contact with a surface on which a reference object is configured, such that optimal lighting of the reference objected is provided and optimal images are received by the image capture device 120 from the lens assembly 110.For example, in exemplary embodiments, each spacer may be sized such that a distance 174 along the longitudinal axis 104 between a front end 172 of each of the plurality of spacers 170 and the front end 142 of the light tube 140 is between approximately 0.25 inches and approximately 0.75 inches, such as between approximately 0.4 inches and approximately 0.5 inches.\",\n \"Thus, each spacer 170 may be sized to space the front end 142 of the light tube 140 from the exterior surface 11 of the turbine component 10 or other object by a distance 176 along the longitudinal axis 104 of between approximately 0.25 inches and approximately 0.75 inches, such as between approximately 0.4 inches and approximately 0.5 inches, when the device 102 is in an operative position in contact with the exterior surface 11 of the turbine component 10 or other object.\",\n \"Device 102 may, in exemplary embodiments, further include an actuator 180.Actuator 180 may, for example, be a button, switch, or other suitable component which can be operated to activate other components of the device 102.For example, actuator 180 may be in communication (via a suitable wired or wireless connection) with the image capture device 120 and the light source 130.When the actuator 180 is actuated to activate the image capture device 120 and the light source 130, the light emitting components 132 may be activated to emit light and the image capture device 120 may be activated to receive one or more images.\",\n \"These components may then be deactivated, either automatically or manually due to additional actuation of the actuator 180.Device 102 may additionally include a shell 190 which generally surrounds and contains various other components of the device 102.For example, shell 190 may surround the lens assembly 110, the image capture device 120, the light source 130, and the light tube 140.Shell 190 may further surround the actuator 180, which may be actuatable through the shell 190, or the actuator 180 may protrude through the shell 190.Notably, the front ends 172 of the spacers 170 may extend outwardly from the shell 190 along the longitudinal axis 104, to space the shell 190 from a surface when the device 102 is in an operative position as discussed.\",\n \"It should be noted that, in exemplary embodiments, devices 102 as discussed herein are hand-held devices which may be manually operated for image analysis as discussed herein.\",\n \"However, it should be understood that the present disclosure is not limited to hand-held devices.\",\n \"Rather, any suitable devices, including for example automated devices and/or devices attached to, for example, robotic machines, etc., and which are manually operated or automated, are within the scope and spirit of the present disclosure.\",\n \"Referring now to FIGS.\",\n \"8 and 9, the present disclosure is further directed to methods 300 for analyzing reference objects, such as passive strain indicators 40.In exemplary embodiments, an image capture device 120 may be utilized to obtain images that are analyzed via a method 300 in accordance with the present disclosure.\",\n \"However, it should be understood that the present disclosure is not limited image capture devices 120 and images captured therefrom, and rather that any suitable images of references objects may be analyzed in accordance with the present disclosure.\",\n \"As mentioned, an image capture device 120 may be in communication with suitable hardware and/or software, via for example a suitable wired or wireless connection, for storing and analyzing the images from the image capture device 120 and device 102 generally.\",\n \"Accordingly, an image capture device 120 may further include a processor 200 which may include such suitable hardware and/or software.\",\n \"In exemplary embodiments, processor 200 may perform various of the steps of method 300 as discussed herein.\",\n \"In general, as used herein, the term “processor” refers not only to integrated circuits referred to in the art as being included in a computer, but also refers to a controller, a microcontroller, a microcomputer, a programmable logic controller (PLC), an application specific integrated circuit, and other programmable circuits.\",\n \"Processor 200 may also include various input/output channels for receiving inputs from and sending control signals to various other components with which the processor 200 is in communication, such as the lens assembly 110, light source 130, image capture device 200, etc.\",\n \"Method 300 may include, for example, the step 310 of locating a reference object portion 314 (such as a passive strain indicator portion 314) relative to a background portion 316 within an image 312 of the reference object (such as the passive strain indicator 40) by performing a first analysis of the image 312.The first analysis is generally an analysis which differentiates the reference object portion 314 from the background portion 316 on the basis of differences in color depth.\",\n \"First analysis may be performed on each individual pixel 318 or groups of pixels 319 defining the image 312.For example, in exemplary embodiments, a binary color depth analysis is performed on multi-pixel groups 319.For a binary analysis to occur, the number of bits-per-pixel of the image i.e.\",\n \"128, 256, etc., is divided into two groups (generally a group which includes the lighter color depths and a group which includes the darker color depths).\",\n \"Each group is categorized as a reference object portion 314 or a background portion 316.For example, the binary color depth analysis may categorize pixels or multi-pixel groups 319 that are darker color depths as denoting a reference object portion 314, and may categorize pixels or multi-pixel groups 319 that are lighter color depths as denoting a background portion 316.In alternative embodiments, first analysis need not be a binary analysis.\",\n \"For example, first analysis may be a suitable greyscale analysis, as discussed herein, or other suitable comparison of color depths of the pixels 318 defining the image 312.Step 310 may generally locate the reference object portion 314 within the image 312.Further, in some embodiments, the information obtained from the first analysis may then be compared to predetermined threshold(s) for such information to determine if the threshold is satisfied.\",\n \"A predetermined threshold may, for example, include one or more dimensions of the reference object, desired locations and orientation of the reference object portion 314 in the plane of the image 312, etc.\",\n \"In some embodiments, if the predetermined threshold is satisfied, feedback signals may be provided to the device 102 to indicate such satisfaction.\",\n \"For example, indicator lights 195 may be activated.\",\n \"Method 300 may further include, for example, the step 320 of identifying reference object indicia (such as passive strain indicator indicia) of the reference object portion 314 by performing a second analysis of the image 312 (such as the entire image 312 or the reference object portion 314 thereof).\",\n \"For passive strain indicators 40, passive strain indicator indicia may include, for example, reference points 41, 42, unique identifiers 47, and other identifiable components of the passive strain indicators 40.In general, reference object indicia are identifiable components of the reference object which provide some information about the reference object.\",\n \"The second analysis is generally an analysis which further differentiates the reference object portion 314 from the background portion 316, and which differentiates the various reference object indicia, on the basis of differences in color depth.\",\n \"Second analysis may be performed on each individual pixel 318 or groups of pixels 319 defining the image 312.For example, in exemplary embodiments, a binary color depth analysis is performed on single pixels 318.In alternative embodiments, second analysis need not be a binary analysis.\",\n \"For example, second analysis may be a suitable greyscale analysis, as discussed herein, or other suitable comparison of color depths of the pixels 318 defining the image 312.Step 320 may generally further locate the reference object portion 314 within the image 312, and may further facilitate collection of information from the reference object of which the image 312 was taken.\",\n \"For example, the existence of reference points 41, 42 may be confirmed, and identifying information for the reference object may be collected from the unique identifiers 47.Further, in some embodiments, the information obtained from the second analysis may then be compared to predetermined threshold(s) for such information to determine if the threshold is satisfied.\",\n \"A predetermined threshold may, for example, include predetermined levels of indicia, such as reference points 41, 42, which can be confirmed.\",\n \"Method 300 may further include, for example, the step 330 of conducting a quality analysis of the reference object portion 314 by performing a third analysis of the image 312 (such as the entire image 312 or the reference object portion 314 thereof).\",\n \"The third analysis is generally an analysis which further differentiates the reference object portion 314 from the background portion 316, and which further differentiates the various reference object indicia, on the basis of differences in color depth.\",\n \"In exemplary embodiments, third analysis utilizes a higher bit-depth than the first analysis.\",\n \"Further, in some embodiments, third analysis may utilize a higher bit-depth than the second analysis.\",\n \"Third analysis may be performed on each individual pixel 318, or on sub-sections of individual pixels.\",\n \"For example, pixels 318 may be divided into 100 sub-sections, 1000 sub-sections, 10,000 sub-sections, or any other suitable number of subsections, and the third analysis may be performed on each individual sub-section.\",\n \"In exemplary embodiments, a greyscale analysis is performed on the bits-per-pixel of the image i.e.\",\n \"128, 256, etc.\",\n \"For example, in some embodiments, a 256 bit-per-pixel greyscale analysis is performed.\",\n \"Accordingly, each pixel 318 or sub-section thereof is categorized as having a particular color depth per the 128, 256, etc.\",\n \"color depth scale.\",\n \"Step 330 may generally allow for the strength of the image 312 to be analyzed by, for example, analyzing the contrast between neighboring pixels 318 or sub-sections thereof.\",\n \"For example, it is generally desirable for the contrast between pixels at the border of features of the reference object portion 314, such as the edges of the reference object portion 314 or indicia thereof, to be high, thus indicating the distinction between the reference object portion 314 or indicia thereof and the background portion 316, etc.\",\n \"Further, step 330 may generally allow for the sharpness of the image 312 to be analyzed by, for example, analyzing the width in pixels 318 or sub-sections thereof of various features of the reference object portion 314.For example, it is generally desirable for the width of features of the reference object portion 314, such as the edges of the reference object portion 314 or indicia thereof, to be low, thus indicating the sharpness of the image of the reference object portion 314 or indicia thereof relative to the background portion 316, etc.\",\n \"Further, in some embodiment, the information obtained from the third analysis may then be compared to predetermined threshold(s) for such information to determine if the threshold is satisfied.\",\n \"A predetermined threshold may, for example, include predetermined strength and sharpness levels.\",\n \"Steps 310, 320 and/or 330 may generally be utilized to determine whether an image 312 is of sufficient quality to be saved for subsequent analysis, such as subsequent strain analysis as discussed herein.\",\n \"For example, as discussed, in some embodiments, the information obtained from the color analyses in each step 310, 320, 330 may compared to various predetermined thresholds.\",\n \"In exemplary embodiments, method 300 may further include the step 340 of saving the image 312 when the locating step 310, the identifying step 320 and/or the conducting step 330 each satisfy the required predetermined threshold(s).\",\n \"Such image 312 may then be utilized in subsequent analysis of the reference object.\",\n \"In some embodiments, method 300 may further include the step 350 of comparing the saved image 312 to one or more previously-saved images 312.The previously-saved images 312 are generally images 312 that have been saved within the same iteration of reference object analysis, i.e.\",\n \"during the same operation of the device 102 and processor 200 to obtain images during a particular time period.\",\n \"In general, differences between the reference object portions 314, such as differences between the indicia thereof, may be analyzed.\",\n \"Optimally, little or no differences should be present, because the images are taken during a single iteration.\",\n \"In general, a threshold may be set for particular differences, such as a threshold strain.\",\n \"For example, a threshold strain may be 5 microstrain, 10 microstrain, 20 microstrain, etc.\",\n \"If a difference exceeds the threshold, this may indicate that outside forces are influencing the accuracy of the images, thus allowing a user to cease analysis and perform a quality check of the associated system 100, device 102, processor 200, etc.\",\n \"It should be noted that steps 310, 320 and/or 330 as discussed herein may in exemplary embodiments, be performed in real time as images are received by the processor 200 from image captures device 120.Method 300 may further include various steps for initially operating a device, such as device 102, to analyze a reference object.\",\n \"For example, method 300 may include the step 360 of activating a light source, such as light source 130.Light source 130 may be activated (such as by processor 200) either automatically within an automated system or manually in response to an input by a user, such by a user pressing actuator 180.Further, method 300 may include the step 370 of activating the processor 200 to analyze images.\",\n \"In accordance with this step, the processor 200 may enter a mode wherein steps 310, 320 and/or 330 are performed.\",\n \"Such activation may occur (such as by processor 200) either automatically within an automated system or manually in response to an input by a user, such by a user pressing actuator 180.Further, method 300 may include the step 380 of contacting the exterior surface on which the reference object is configured, such as the exterior surface 11 of the turbine component 10, with a device such as device 102.In exemplary embodiments as discussed herein, spacers 170 may contact the exterior surface 11.Such contact may occur either automatically within an automated system (such as by processor 200) or manually by a user.\",\n \"Notably, in exemplary embodiments, step 370 may occur after step 360.Steps 310-350 may occur after such steps.\",\n \"This written description uses examples to disclose the invention, including the best mode, and also to enable any person skilled in the art to practice the invention, including making and using any devices or systems and performing any incorporated methods.\",\n \"The patentable scope of the invention is defined by the claims, and may include other examples that occur to those skilled in the art.\",\n \"Such other examples are intended to be within the scope of the claims if they include structural elements that do not differ from the literal language of the claims, or if they include equivalent structural elements with insubstantial differences from the literal languages of the claims.\"\n ]\n]"},"source":{"kind":"string","value":"Patent_15872034"}}},{"rowIdx":4493990,"cells":{"text":{"kind":"list like","value":[["Novel Systems, Methods And Compositions Involving Plant Life Enhancing Products","A method for producing a plant life enhancing product is described.","The method includes: (i) anaerobically digesting agricultural residue to produce an anaerobically activated organic residue and an ammonia-enriched water; (ii) aerobically digesting the ammonia-enriched water to produce an aerobically activated organic residue; and (iii) blending the anaerobically activated organic residue with the aerobically activated organic residue to produce the plant life enhancing product."],["1.A method for producing a plant life enhancing product, said method comprising; anaerobically digesting agricultural residue to produce an anaerobically activated organic residue and an ammonia-enriched water; aerobically digesting said ammonia-enriched water to produce an aerobically activated organic residue; and blending said anaerobically activated organic residue with said aerobically activated organic residue to produce said plant life enhancing product.","2.The method of claim 1, wherein said anaerobically activated organic residue is blended following said anaerobically digesting agricultural residue.","3.The method of claim 1, further comprising drying said plant life enhancing product to form a dried plant life enhancing product.","4.The method of claim 3, further comprising pelletizing said dried plant life enhancing product.","5.The method of claim 1, wherein said plant life enhancing product is used as at least one member selected from a group comprising biocide, pesticide, and agricultural feed product.","6.The method of claim 1, further comprising removing solids from anaerobically activated organic residue.","7.The method of claim 6, wherein said removing solids includes removing at least one member selected from a group comprising coarse solids, medium-sized solids, and fine solids."],[" BACKGROUND Large volumes of water are used in the operation of dairies and farms, where crops and animals are raised.","The resulting wastewater is mainly organic in nature and nutrient rich.","Moreover, a significant amount of organics and/or nutrients are in the form of complex molecules that are not readily absorbed by plants and animals.","To keep up with a diminishing water supply in some regions and lower water and energy costs, attempted wastewater treatment solutions are passive in nature and offer no effective solution to recover the nutrients.","The attempted solutions also fail to provide nutrients in a form that may be used by the plants and animals."],[" SUMMARY In view of the foregoing, the present teachings offer novel systems and methods for wastewater treatment and byproducts that provide plant and animal life enhancing products.","In one aspect, the present teachings provide a system for producing plant life enhancing product.","The system includes: (i) an anaerobic tank for anaerobically digesting agricultural residue to produce an anaerobically activated organic residue and an ammonia-enriched water; (ii) a solids removal sub-assembly for separating the ammonia-enriched water from the anaerobically activated organic residue to produce a substantially ammonia-free anaerobically activated organic residue; (iii) an aerobic tank for aerobically digesting the ammonia-enriched water to produce an aerobically activated organic residue; and (iv) a blending unit for blending the anaerobically activated organic residue with aerobically activated organic residue to produce the plant life enhancing product.","In another aspect, the present teachings provide a method for producing a plant life enhancing product.","The method includes: (i) anaerobically digesting agricultural residue to produce an anaerobically activated organic residue and an ammonia-enriched water; (ii) aerobically digesting the ammonia-enriched water to produce an aerobically activated organic residue; and (iii) blending the anaerobically activated organic residue with the aerobically activated organic residue to produce the plant life enhancing product.","In yet another aspect, the present teachings provide a plant life enhancing composition.","The plant life enhancing component includes: (i) an effective amount of a bioavailable component that is available for immediate absorption by a plant; (ii) an effective amount of a precursor component, which has a more complex molecular structure than the bioavailable component and over a duration transforms into the bioavailable component; and (iii) an effective amount of a catalyst that facilitates transformation of the precursor component to the bioavailable component.","In yet another aspect, the present teachings provide another plant life enhancing composition comprising: (i) an effective amount of a dormant component, which includes an output of aerobic digestion; (ii) an effective amount of a decomposed dormant component, which includes an output of anaerobic digestion; and (iii) an effective amount of a catalyst that facilitates transformation of the dormant component to the decomposed dormant component.","Conventional wastewater treatments typically release noxious gases into the environment, contributing to the greenhouse effect.","The present teachings provide novel systems and methods for capturing those gases, converting those gases into useful energy, and doing so preferably in a substantially closed system.","It is an objective, among many, of the present teachings to convert otherwise harmful byproducts to useful energy, preferably using some of the treated water resulting from wastewater treatment.","The approach adopted by the present teachings recognizes, among other things, that the concept of biochemical oxygen demand (“BOD”) drives various steps of wastewater treatment.","BOD is a well-known parameter, which indicates the amount of oxygen needed to biologically stabilize the organic matter present.","According to preferred embodiments of the present teachings, efforts to effectively control BOD levels in various stages of wastewater treatment rely upon more than gravity and time.","This allows the present teachings to offer active treatment of wastewater, as opposed to prior art's passive treatment, which relies only upon gravity and time.","Organic matter commonly present in wastewater uses oxygen for various reasons and as a result, depletes soluble oxygen.","A requisite high level of dissolved oxygen, however, is desirable during certain stages of treatment to grow microorganisms to consume organic matter present in wastewater treatment.","Conventional methods only in a single discrete step grow microorganisms by introducing oxygen to replenish the depleted levels of oxygen in wastewater.","This step provides oxygen to initially promote growth of naturally occurring microorganisms to large numbers so that they consume almost all of the organic matter and oxygen in wastewater.","Conventional methods introduce oxygen by implementing passive means, i.e., requiring a large space-consuming tank to expose a greater surface area to the atmosphere for long periods of time.","The present teachings recognize the need to maximize use of high-pressure air diffusion in multiple steps to actively increase the amount of dissolved oxygen in wastewater as well as creating an active environment for naturally occurring and custom introduced bacteria to grow by increasing the surface-area-to-volume ratio in specific reactors.","In preferred embodiments of the present teachings, this process of actively introducing oxygen and increasing surface-area-to-volume ratio begins early, during a solids-removal stage, and well before microorganisms growth is encouraged in conventional methods.","When sufficient amount of microorganisms die in an oxygen- and nutrient-poor environment, dead organisms undergo decay, raising levels of ammonia, nitrate, and nitrite through a process known as “nitrification.” Conventional treatment discharges the wastewater with a high concentration of nitrogen and phosphorous to the environment.","Reverse osmosis and ion exchange are known to remove nitrogen and phosphorous, but are not deemed commercially viable and are therefore not integrated into conventional wastewater treatment methods.","Discharge of nutrient-rich effluent is known to be injurious to life.","Nitrates are carcinogenic and direct discharge of wastewater with nitrates may contaminate drinking water aquifers.","The present teachings recognize this and prevents such contamination by effectively removing nitrogen and phosphorous from wastewater before discharge.","Preferred embodiments of the present teachings effectively treat wastewater by driving down BOD, maintaining the level of dissolved oxygen, lowering the solid content, and controlling the nutrient level in wastewater at various stages.","By way of example, in one stage, the present teachings drive down BOD and solid content in wastewater by actively focusing on the removal of BOD-contributing solids.","As another example, during the process of removing solids, the present teachings also focus on improving the growth regime for naturally occurring and genetically engineered bacteria.","Preferred embodiments of the present teachings use high-pressure air diffusion to substantially maintain or increase the level of dissolved oxygen in wastewater.","As a result, according to preferred embodiments of the present teachings, microorganism growth is encouraged well before they are employed to remove organic matter.","As yet another example, directly after removal of organic matter by microorganism consumption, preferred embodiments treat wastewater by creating anaerobic conditions to achieve complete microorganism die off and lower solid content or reduce BOD in wastewater.","Next, the wastewater is treated to remove solids and further reduce BOD in an aerobic environment, which replenishes the dissolved oxygen levels.","As yet another example, preferred embodiments of the present teachings, while actively removing BOD-contributing solids, dead microorganisms, nutrients, algae, and other solids, maintain the level of dissolved oxygen in wastewater to prevent an increase of BOD and solid content by reversible reaction.","It is important to note that prior art fails to recognize drawbacks of reversible reactions, which increase BOD, let alone offer provisions to prevent increase of BOD.","As yet another example, preferred embodiments of the present teachings drive down the nutrients in wastewater by actively focusing on the removal of all forms of nitrogen and phosphates by effectively cultivating specific biological processes that utilize nutrients available for their own growth.","The teachings further reduce the nutrient load by actively removing any biological matter remaining in the effluent.","As yet another example, the present teachings offer provisions to capture methane and other components of biogas to convert methane into electricity and to convert other components of biogas and byproducts of the electricity conversion process to chemical species, which promote growth or production of useful products.","In preferred embodiments of the present teachings, a portion of treated water resulting from wastewater treatment is used in conjunction with biogas and gases produced during anaerobic and aerobic digestion, respectively, in a useful manner as opposed to releasing such gases to the atmosphere, as conventional processes do.","In yet another aspect, the present teachings provide a method for removing methane from biogas.","The method includes: (i) receiving biogas including methane and other components into a first tank; (ii) receiving water into the first tank; (iii) contacting the biogas with the water inside the first tank; (iv) dispensing methane gas from an outlet of the first tank; and (v) producing from the tank an effluent stream that includes other components of the biogas.","The step of contacting may include passing bubbles of biogas through the water.","Water may be obtained from any source of purified water.","Preferably, however, water is obtained from a wastewater treatment facility.","In one embodiment of the present teachings, the inventive methods may further include a step of carrying out digestion of water enriched with organic matter in a second tank to produce the biogas.","The second tank may be different from the first tank.","The organic matter in the water may be between about 0.5% by volume and about 25% by volume.","In preferred embodiments of the present teachings, inventive methods include a step of sending the effluent stream from the tank to a diffused air flotation (“DAF”) tank that is designed to effect removal of solids.","Inventive methods may further include a step of sending the methane gas to an electrical generator that is designed to burn methane gas and produce electrical energy.","Preferably, the electrical generator produces exhaust gases which include at least one of CO 2 gas, SO x gas, and NO x gas, and are treated in a third tank by contacting the exhaust gases with water to remove at least one of CO 2 gas, SO x gas, and NO x gas from the third tank and produce water having dissolved therein at least one of CO 2 gas, SO x gas, and NO x gas.","More preferably, the water having dissolved therein at least one of CO 2 gas, SO x gas, and NO x gas is delivered to an algal pond.","The algal pond may be a high rate algal pond (“HRAP”).","In yet another aspect, the present teachings provide a method for removing byproduct gases after aerobic digestion.","The method includes: (i) receiving into a first tank a gaseous mixture including at least one of ammonia gas and sulfur gas; (ii) receiving water into the first tank; (iii) contacting the gaseous mixture including at least one of the ammonia gas and the sulfur gas with the water inside the first tank to produce an effluent stream of water having dissolved therein the at least one of aqueous ammonia and sulfur and produce a residual gaseous mixture including at least one of ammonia gas and sulfur gas; (iv) dispensing residual gas including at least one of residual ammonia gas and residual sulfur gas; and (v) discharging the effluent stream including water which has dissolved therein the at least one of aqueous ammonia and sulfur gas.","Residual gaseous mixture refers to the gas or gases that do not dissolve in water.","The step of dispensing may include recirculating the residual gaseous mixture from outlet of the first tank to an inlet of the first tank.","The step of contacting may include passing bubbles of the gaseous mixture through the water.","In yet another aspect, the present teachings provide a system for removing byproducts of anaerobic digestion.","The system includes: (i) a first tank including: (a) a first inlet that is connected to receive byproduct gases of anaerobic digestion including at least one gas and methane, (b) a first outlet that provides methane gas as exhaust, (c) a second inlet that is connected to receive a stream of water, and (d) a second outlet that discharges an effluent water stream having dissolved therein the above-mentioned at least one gas into a tank designed for removing solids; and (ii) an electrical generator that is connected to the first outlet of the first tank; and wherein the first tank is designed to contact the stream of water with the byproduct gases of anaerobic digestion and produce the effluent stream of water.","In preferred embodiments, the electrical generator produces electricity and a gas including at least one of CO 2 gas, SO x gas, and NO x gas.","In yet another aspect, the present teachings provide a system for wastewater treatment.","The system includes: (i) a solids-removal subassembly designed to remove solids from wastewater and produce solids-depleted water; (ii) an assembly designed for processing organic material in the solids-depleted wastewater to produce treated water and the assembly connected to the solids-removal subassembly; (iii) a tank that has a first inlet, a first outlet, and a second outlet; and (iv) wherein the first inlet of the tank is designed to receive treated water, the first outlet is designed to discharge a first portion of treated water, the second outlet is designed to discharge a second portion of treated water, and the first portion of treated water is used for processing byproduct gases resulting from wastewater treatment.","Preferably, the tank may be a holding tank that is located downstream from a nutrient-removal tank, which is designed to remove nutrients from wastewater.","In alternative embodiments of the present teachings, the tank is a nutrient-removal tank designed to remove nutrients from wastewater In yet another aspect, the present teachings provide a method of wastewater treatment.","The method includes the steps of: (i) removing solids from wastewater to produce solids-depleted water; (ii) processing organic material in the solids-depleted wastewater to produce treated water; (iii) discharging a first portion of treated water and a second portion of treated water; and (iv) using the first portion of treated water to process byproduct gases resulting from wastewater treatment.","In preferred embodiments, the present teachings provide the further step of removing nutrients from wastewater.","The above-mentioned step of using may be carried out after removing nutrients.","The construction and method of operation of the teachings, however, together with additional objects and advantages thereof will be best understood from the following descriptions of specific embodiments when read in connection with the accompanying figures."],["RELATED APPLICATION This application claims priority to U.S.","Provisional Application No.","61/727,097, filed on Nov. 15, 2012, entitled “Novel Systems And Methods For Treatment Of Gaseous And Solid Byproducts Of Wastewater Treatment”, which is related to U.S. patent application Ser.","No.","13/750,989, filed Jan. 25, 2013, entitled “Novel Systems And Methods For Converting Gaseous Byproducts Of Wastewater Treatment Into Energy”, which claims priority to and is a divisional of U.S. patent application Ser.","No.","12/577,129 filed on Oct. 9, 2009, which is now U.S. Pat.","No.","8,382,983, issued Feb. 26, 2013, all of which are incorporated herein for all purposes.","FIELD The present teachings relate generally to wastewater treatment and byproducts thereof.","More particularly, the present teachings relate to novel systems, methods and compositions involving plant life enhancing products produced from wastewater treatment and/or byproducts thereof.","BACKGROUND Large volumes of water are used in the operation of dairies and farms, where crops and animals are raised.","The resulting wastewater is mainly organic in nature and nutrient rich.","Moreover, a significant amount of organics and/or nutrients are in the form of complex molecules that are not readily absorbed by plants and animals.","To keep up with a diminishing water supply in some regions and lower water and energy costs, attempted wastewater treatment solutions are passive in nature and offer no effective solution to recover the nutrients.","The attempted solutions also fail to provide nutrients in a form that may be used by the plants and animals.","SUMMARY In view of the foregoing, the present teachings offer novel systems and methods for wastewater treatment and byproducts that provide plant and animal life enhancing products.","In one aspect, the present teachings provide a system for producing plant life enhancing product.","The system includes: (i) an anaerobic tank for anaerobically digesting agricultural residue to produce an anaerobically activated organic residue and an ammonia-enriched water; (ii) a solids removal sub-assembly for separating the ammonia-enriched water from the anaerobically activated organic residue to produce a substantially ammonia-free anaerobically activated organic residue; (iii) an aerobic tank for aerobically digesting the ammonia-enriched water to produce an aerobically activated organic residue; and (iv) a blending unit for blending the anaerobically activated organic residue with aerobically activated organic residue to produce the plant life enhancing product.","In another aspect, the present teachings provide a method for producing a plant life enhancing product.","The method includes: (i) anaerobically digesting agricultural residue to produce an anaerobically activated organic residue and an ammonia-enriched water; (ii) aerobically digesting the ammonia-enriched water to produce an aerobically activated organic residue; and (iii) blending the anaerobically activated organic residue with the aerobically activated organic residue to produce the plant life enhancing product.","In yet another aspect, the present teachings provide a plant life enhancing composition.","The plant life enhancing component includes: (i) an effective amount of a bioavailable component that is available for immediate absorption by a plant; (ii) an effective amount of a precursor component, which has a more complex molecular structure than the bioavailable component and over a duration transforms into the bioavailable component; and (iii) an effective amount of a catalyst that facilitates transformation of the precursor component to the bioavailable component.","In yet another aspect, the present teachings provide another plant life enhancing composition comprising: (i) an effective amount of a dormant component, which includes an output of aerobic digestion; (ii) an effective amount of a decomposed dormant component, which includes an output of anaerobic digestion; and (iii) an effective amount of a catalyst that facilitates transformation of the dormant component to the decomposed dormant component.","Conventional wastewater treatments typically release noxious gases into the environment, contributing to the greenhouse effect.","The present teachings provide novel systems and methods for capturing those gases, converting those gases into useful energy, and doing so preferably in a substantially closed system.","It is an objective, among many, of the present teachings to convert otherwise harmful byproducts to useful energy, preferably using some of the treated water resulting from wastewater treatment.","The approach adopted by the present teachings recognizes, among other things, that the concept of biochemical oxygen demand (“BOD”) drives various steps of wastewater treatment.","BOD is a well-known parameter, which indicates the amount of oxygen needed to biologically stabilize the organic matter present.","According to preferred embodiments of the present teachings, efforts to effectively control BOD levels in various stages of wastewater treatment rely upon more than gravity and time.","This allows the present teachings to offer active treatment of wastewater, as opposed to prior art's passive treatment, which relies only upon gravity and time.","Organic matter commonly present in wastewater uses oxygen for various reasons and as a result, depletes soluble oxygen.","A requisite high level of dissolved oxygen, however, is desirable during certain stages of treatment to grow microorganisms to consume organic matter present in wastewater treatment.","Conventional methods only in a single discrete step grow microorganisms by introducing oxygen to replenish the depleted levels of oxygen in wastewater.","This step provides oxygen to initially promote growth of naturally occurring microorganisms to large numbers so that they consume almost all of the organic matter and oxygen in wastewater.","Conventional methods introduce oxygen by implementing passive means, i.e., requiring a large space-consuming tank to expose a greater surface area to the atmosphere for long periods of time.","The present teachings recognize the need to maximize use of high-pressure air diffusion in multiple steps to actively increase the amount of dissolved oxygen in wastewater as well as creating an active environment for naturally occurring and custom introduced bacteria to grow by increasing the surface-area-to-volume ratio in specific reactors.","In preferred embodiments of the present teachings, this process of actively introducing oxygen and increasing surface-area-to-volume ratio begins early, during a solids-removal stage, and well before microorganisms growth is encouraged in conventional methods.","When sufficient amount of microorganisms die in an oxygen- and nutrient-poor environment, dead organisms undergo decay, raising levels of ammonia, nitrate, and nitrite through a process known as “nitrification.” Conventional treatment discharges the wastewater with a high concentration of nitrogen and phosphorous to the environment.","Reverse osmosis and ion exchange are known to remove nitrogen and phosphorous, but are not deemed commercially viable and are therefore not integrated into conventional wastewater treatment methods.","Discharge of nutrient-rich effluent is known to be injurious to life.","Nitrates are carcinogenic and direct discharge of wastewater with nitrates may contaminate drinking water aquifers.","The present teachings recognize this and prevents such contamination by effectively removing nitrogen and phosphorous from wastewater before discharge.","Preferred embodiments of the present teachings effectively treat wastewater by driving down BOD, maintaining the level of dissolved oxygen, lowering the solid content, and controlling the nutrient level in wastewater at various stages.","By way of example, in one stage, the present teachings drive down BOD and solid content in wastewater by actively focusing on the removal of BOD-contributing solids.","As another example, during the process of removing solids, the present teachings also focus on improving the growth regime for naturally occurring and genetically engineered bacteria.","Preferred embodiments of the present teachings use high-pressure air diffusion to substantially maintain or increase the level of dissolved oxygen in wastewater.","As a result, according to preferred embodiments of the present teachings, microorganism growth is encouraged well before they are employed to remove organic matter.","As yet another example, directly after removal of organic matter by microorganism consumption, preferred embodiments treat wastewater by creating anaerobic conditions to achieve complete microorganism die off and lower solid content or reduce BOD in wastewater.","Next, the wastewater is treated to remove solids and further reduce BOD in an aerobic environment, which replenishes the dissolved oxygen levels.","As yet another example, preferred embodiments of the present teachings, while actively removing BOD-contributing solids, dead microorganisms, nutrients, algae, and other solids, maintain the level of dissolved oxygen in wastewater to prevent an increase of BOD and solid content by reversible reaction.","It is important to note that prior art fails to recognize drawbacks of reversible reactions, which increase BOD, let alone offer provisions to prevent increase of BOD.","As yet another example, preferred embodiments of the present teachings drive down the nutrients in wastewater by actively focusing on the removal of all forms of nitrogen and phosphates by effectively cultivating specific biological processes that utilize nutrients available for their own growth.","The teachings further reduce the nutrient load by actively removing any biological matter remaining in the effluent.","As yet another example, the present teachings offer provisions to capture methane and other components of biogas to convert methane into electricity and to convert other components of biogas and byproducts of the electricity conversion process to chemical species, which promote growth or production of useful products.","In preferred embodiments of the present teachings, a portion of treated water resulting from wastewater treatment is used in conjunction with biogas and gases produced during anaerobic and aerobic digestion, respectively, in a useful manner as opposed to releasing such gases to the atmosphere, as conventional processes do.","In yet another aspect, the present teachings provide a method for removing methane from biogas.","The method includes: (i) receiving biogas including methane and other components into a first tank; (ii) receiving water into the first tank; (iii) contacting the biogas with the water inside the first tank; (iv) dispensing methane gas from an outlet of the first tank; and (v) producing from the tank an effluent stream that includes other components of the biogas.","The step of contacting may include passing bubbles of biogas through the water.","Water may be obtained from any source of purified water.","Preferably, however, water is obtained from a wastewater treatment facility.","In one embodiment of the present teachings, the inventive methods may further include a step of carrying out digestion of water enriched with organic matter in a second tank to produce the biogas.","The second tank may be different from the first tank.","The organic matter in the water may be between about 0.5% by volume and about 25% by volume.","In preferred embodiments of the present teachings, inventive methods include a step of sending the effluent stream from the tank to a diffused air flotation (“DAF”) tank that is designed to effect removal of solids.","Inventive methods may further include a step of sending the methane gas to an electrical generator that is designed to burn methane gas and produce electrical energy.","Preferably, the electrical generator produces exhaust gases which include at least one of CO2 gas, SOx gas, and NOx gas, and are treated in a third tank by contacting the exhaust gases with water to remove at least one of CO2 gas, SOx gas, and NOx gas from the third tank and produce water having dissolved therein at least one of CO2 gas, SOx gas, and NOx gas.","More preferably, the water having dissolved therein at least one of CO2 gas, SOx gas, and NOx gas is delivered to an algal pond.","The algal pond may be a high rate algal pond (“HRAP”).","In yet another aspect, the present teachings provide a method for removing byproduct gases after aerobic digestion.","The method includes: (i) receiving into a first tank a gaseous mixture including at least one of ammonia gas and sulfur gas; (ii) receiving water into the first tank; (iii) contacting the gaseous mixture including at least one of the ammonia gas and the sulfur gas with the water inside the first tank to produce an effluent stream of water having dissolved therein the at least one of aqueous ammonia and sulfur and produce a residual gaseous mixture including at least one of ammonia gas and sulfur gas; (iv) dispensing residual gas including at least one of residual ammonia gas and residual sulfur gas; and (v) discharging the effluent stream including water which has dissolved therein the at least one of aqueous ammonia and sulfur gas.","Residual gaseous mixture refers to the gas or gases that do not dissolve in water.","The step of dispensing may include recirculating the residual gaseous mixture from outlet of the first tank to an inlet of the first tank.","The step of contacting may include passing bubbles of the gaseous mixture through the water.","In yet another aspect, the present teachings provide a system for removing byproducts of anaerobic digestion.","The system includes: (i) a first tank including: (a) a first inlet that is connected to receive byproduct gases of anaerobic digestion including at least one gas and methane, (b) a first outlet that provides methane gas as exhaust, (c) a second inlet that is connected to receive a stream of water, and (d) a second outlet that discharges an effluent water stream having dissolved therein the above-mentioned at least one gas into a tank designed for removing solids; and (ii) an electrical generator that is connected to the first outlet of the first tank; and wherein the first tank is designed to contact the stream of water with the byproduct gases of anaerobic digestion and produce the effluent stream of water.","In preferred embodiments, the electrical generator produces electricity and a gas including at least one of CO2 gas, SOx gas, and NOx gas.","In yet another aspect, the present teachings provide a system for wastewater treatment.","The system includes: (i) a solids-removal subassembly designed to remove solids from wastewater and produce solids-depleted water; (ii) an assembly designed for processing organic material in the solids-depleted wastewater to produce treated water and the assembly connected to the solids-removal subassembly; (iii) a tank that has a first inlet, a first outlet, and a second outlet; and (iv) wherein the first inlet of the tank is designed to receive treated water, the first outlet is designed to discharge a first portion of treated water, the second outlet is designed to discharge a second portion of treated water, and the first portion of treated water is used for processing byproduct gases resulting from wastewater treatment.","Preferably, the tank may be a holding tank that is located downstream from a nutrient-removal tank, which is designed to remove nutrients from wastewater.","In alternative embodiments of the present teachings, the tank is a nutrient-removal tank designed to remove nutrients from wastewater In yet another aspect, the present teachings provide a method of wastewater treatment.","The method includes the steps of: (i) removing solids from wastewater to produce solids-depleted water; (ii) processing organic material in the solids-depleted wastewater to produce treated water; (iii) discharging a first portion of treated water and a second portion of treated water; and (iv) using the first portion of treated water to process byproduct gases resulting from wastewater treatment.","In preferred embodiments, the present teachings provide the further step of removing nutrients from wastewater.","The above-mentioned step of using may be carried out after removing nutrients.","The construction and method of operation of the teachings, however, together with additional objects and advantages thereof will be best understood from the following descriptions of specific embodiments when read in connection with the accompanying figures.","BRIEF DESCRIPTION OF THE DRAWINGS FIG.","1A shows an exemplar system for wastewater treatment, according to one present arrangement.","FIG.","1B shows an exemplar system, according to one embodiment of the present teachings, for separating methane gas from biogas that is produced after anaerobic digestion.","FIG.","1C shows an exemplar system, according to one present arrangement, for treating gas produced by aerobic and anaerobic digestion.","FIG.","2 shows details of a BCR design, according to one present arrangement, used in the system of FIG.","1A.","FIG.","3 shows an exemplar algal pond used in the system of FIG.","1A.","FIG.","4 shows a perspective view of the algal pond of FIG.","3.FIG.","5 shows an exemplar system, according to one present arrangement, for converting methane gas into electricity.","FIG.","6 shows an exemplar system for converting solid byproducts of wastewater treatment into plant life enhancing product, e.g., fertilizer, pesticide, biocide, and/or agricultural feed, according to one present arrangement.","FIG.","7 shows an exemplar flow diagram, according to one present arrangement, for converting solid byproducts of wastewater treatment into plant life enhancing products (e.g., fertilizer, pesticide, biocide, and/or agricultural feed).","DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS In the following description numerous specific details are set forth in order to provide a thorough understanding of the present teachings.","It will be apparent, however, to one skilled in the art that the present teachings may be practiced without limitation to some or all of these specific details.","In other instances, well known process steps have not been described in detail in order to not unnecessarily obscure the teachings.","FIG.","1A shows a system design 100, according to one embodiment of the present teachings, for active treatment of wastewater.","System 100 includes an anaerobic tank 102, inside which anaerobic digestion of wastewater takes place.","In other words, inside anaerobic tank 102, organic content in wastewater is broken down into simpler molecules, which may be further treated by other methods.","A byproduct of anaerobic digestion, biogas 128, is collected at the top surface of anaerobic tank 102 (not shown to simplify illustration) and delivered to a system for treatment resulting in product that may be converted into clean energy (described below with reference to FIGS.","1B and 5).","System design 100 provides wastewater that has undergone anaerobic digestion to a series of active devices for removal of solid waste.","These active devices include a solids separator 104, a DAF tank 106, and a first SRT 108, each of which facilitates removal of solid contaminants of different sizes and type.","The relatively solid-free wastewater is then transported to a series of BCRs 110 and 112 to remove organic matter.","For removal of solid sludge, if necessary, an aerobic sludge digester tank 114 is provided.","Wastewater containing dead microorganisms from either BCR 112 or from aerobic sludge digester 114, if one is employed, is sent to a second SRT 116 for removal of solids, which include for the most part dead microorganisms.","For further removal of dead organisms, the wastewater is treated in DAF tank 106 and from there sent to HRAP 118.HRAP 118 is provided to remove nutrients, such as nitrates, nitrites, and phosphorous from the wastewater.","Next, wastewater is passed again through DAF tank 106 and through a third SRT 120 to specifically remove algae introduced into wastewater from HRAP 118.DAF tank 106 also serves to increase level of dissolved oxygen in wastewater.","The nutrient-and-algae-depleted wastewater is optionally provided to a maturation pond 122 before discharging to the environment.","In maturation pond 122, residual algae not removed in either DAF tank 106 or SRT 120 is removed and treated wastewater is exposed to elements of the natural environment.","In preferred embodiments of the present teachings, a portion of the effluent stream flowing through line 125 from maturation pond 122 facilitates conversion of various byproducts of wastewater treatment (described below with reference to FIGS.","1B and 1C) to useful energy (described below with reference to FIG.","5) or useful downstream products (described below with reference to FIGS.","1B, 1C, and 5).","System 100 also includes various lines or connections between the different tanks to transport residual solids that are removed from the wastewater.","According to FIG.","1A, one such line 124 is provided between DAF tank 106 and anaerobic tank 102 to transport those solids which are not removed after treatment in DAF tank 106 back to a subsystem for drying and pelletizing.","Another line 127 is also provided to transport solids, which typically include dead microorganisms, from aerobic sludge digester 114 to a subsystem designed for drying and pelletizing.","The resulting pellets are used for fertilizer, pesticide, and/or biocide (described below with reference to FIGS.","6 and 7).","According to the embodiment shown in FIG.","1A, residual solids are not only transported from aerobic sludge digester 114, but are also transported to digester 114.Specifically, a line 128 is provided to transport residual solids from DAF tank 106 back to aerobic sludge digester 114.In addition to conveying wastewater at different stages of treatment and conveying residual solids, various lines or connections between the different tanks of system 100 deliver biogas and gas to produce energy and other useful downstream products.","By way of example, a gaseous mixture 128, which includes methane and other gases captured as byproducts of anaerobic digestion inside anaerobic tank 102, is transported to a tank 126 shown in FIG.","1B.","In preferred embodiments of the present teachings, tank 126 is a scrubber designed to contact gaseous mixture 128 with liquid stream 125.As another example, a portion of effluent stream 125 from maturation pond 122 is used to contact gaseous mixture 142 of FIG.","1C.","FIG.","1C, described in greater detail below, shows processing of the gas or gaseous mixture resulting from aerobic digestion.","From tank 126 of FIG.","1B, a line 130 is provided to DAF tank 106 (as shown in FIG.","1A) to deliver an effluent water stream having dissolved therein certain biogas components, such as ammonia, carbon dioxide, hydrogen, and sulfur, but not including methane, for further treatment.","A detailed description of FIG.","1B explains how the effluent entering DAF tank 106 shown in FIG.","1A is produced.","In system 100, gas (which includes ammonia gas and sulfur gas) emanating from processing of organic matter inside BCR 110 (shown in FIG.","1A) is delivered via line 142 to a tank 140.Tank 140 is preferably a scrubber that is configured to contact a portion of treated water 125 (shown in FIGS.","1A and 1B), for example, with the gas generated inside BCR 110.In other embodiments of the present teachings, instead of using a portion of treated water stream 125, any water stream that is relatively pure may be used.","Solids separator 104 comes equipped with a screen designed to remove solids that do not settle out in anaerobic tank 102 or that are pulled into system 100 by the inlet pumps (not shown to simplify illustration of FIG.","1A).","Solids in wastewater that pass through the screen are pressed between at least two belts, each of which is supported by turning rollers positioned throughout the press.","The belts are permeable and allow wastewater to pass through, holding back heavy solids.","Moving action of the belt and the splashing of wastewater, as it permeates the belt, also serve to introduce oxygen into wastewater.","The resulting increased level of dissolved oxygen encourages growth of microorganisms, which remove organic matter in a subsequent step.","Depending on the screen size, solids separator 104 removes between about 75% and about 98% of solids removed from wastewater, which at this stage of treatment typically has a solid content that is between about 15% and about 30%.","Eliminating these solids represents a significant amount of BOD removal.","Solids removed by the press may be composted or otherwise removed from the premises for disposal.","Solids separator 104 may be made from any rigid material, but is preferably made from stainless steel.","Similarly, a range of suitable dimensions work well.","In one preferred embodiment of the present teachings, system 100 uses a solids separator commercially available from Press Technologies of Wheat Ridge, Colorado.","DAF tank 106 captures small particulate matter that is not removed by solids separator 104.To effect solid separation from wastewater, DAF tank 106, in accordance with one embodiment of the present teachings, uses a pored diffuser and a high-pressure pump that is preferably fitted with a venturi tube and is designed to introduce air bubbles inside wastewater.","The pump draws in air, forcing air bubbles through the pored diffuser to form micro-air bubbles.","The pored diffuser may be made from stone.","Air is forced through the pored diffuser to produce a diffused air flow, preferably of about 40 cubic feet per minute.","Air bubbles in their upward motion accumulate on the particulate matter and carry with them particulate matter to the top, where they are removed via skimmers.","Air bubbles inside DAF tank provide a large surface area to effectively dissolve oxygen and thereby raise the level of soluble oxygen in wastewater.","As a result, air bubbles not only facilitate removal of solids, but also increase the level of dissolved oxygen in wastewater to promote microorganism growth for subsequent removal of organic matter.","Thus, the present teachings promote conditions for effective removal of organic matter in early stages and well before such removal is the primary focus during subsequent treatment.","In preferred embodiments of the present teachings, DAF tank is commercially available from Martint Environmental of Lexington, S.C. By way of example, a DAF tank used in the present teachings is about 7 feet long, 3.5 feet wide, and 5 feet high.","Hydraulic residence time in a DAF tank may be between about 1 and about 3 hours.","Hydraulic residence time refers to the amount of time it takes for a single molecule of water to pass through the unit from the time it enters a tank, for example, to the time it leaves.","DAF tank removes between about 85% and about 95% of the solids removed from wastewater, which at this point has a solid content that is between about 3% and about 6%.","Unlike conventional solid sedimentation in the prior art, the present teachings do not require solids to fully settle to the bottom of the SRT to be trapped there.","SRT 108 effects separation of residual solids by actively increasing the hydraulic flow path and providing physical impediments to particles for permanently trapping them.","Hydraulic flow path refers to a path that is traversed by wastewater.","An increase in the hydraulic flow path allows for separating a greater amount of solids from wastewater.","SRT 108 is preferably large enough such that it takes wastewater being pumped in at 40 gallons per minute 100 minutes to fill it.","U.S. Pat.","No.","6,899,808, which is incorporated herein by reference for all purposes, describes preferred embodiments of the SRT used in the present teachings.","Surface area inside SRT 108 is preferably between about 160 square feet and about 320 square feet.","SRT removes between about 85% and about 90% of solids having particle sizes greater than 20 micrometers from wastewater, which at this point has a solid content of about 1%.","During the solid removal process, SRT 108 effects diffused air flow to raise level of dissolved oxygen in wastewater and to clean the screens provided for solid removal.","By reducing ROD level and solid content and raising level of dissolved oxygen in wastewater, the present teachings promote conditions for removal of organic matter in early stages and well before such removal is the primary focus during subsequent treatment.","FIG.","2 shows a cross-sectional view of a BCR 200 (e.g., BCRS 110 and 112), in accordance with one embodiment of the present teachings.","BCR 200 includes a tank 202, which contains biological chips 214 and has an inlet 208 for providing wastewater (not shown to simplify illustration) for treatment.","Tank 202 is equipped with a blower 204 which introduces air inside wastewater.","Waste solids in wastewater form a layer 212 and are removed by a pump 210.Biological chips 214 and blower 204 serve to provide wastewater with very high dissolved oxygen concentration and a high surface-area-to-volume ratio to aid the metabolic growth rates of microorganisms (not shown in FIG.","2 to simplify illustration).","BCR is an aerobic treatment system that utilizes microorganisms attached to biologic chips to form a biological film or slime layer (typically ranging from 0.1 mm to 0.2 mm thick).","Microorganisms in the outer part of slime layer degrade the organic material in wastewater.","However, as the slime layer thickens, oxygen is unable to penetrate the biological chips and anaerobic organisms develop.","Eventually the microorganisms near the surface lose their ability to cling to the biological chips, and a portion of the slime layer falls off.","In accordance with one embodiment of the present teachings, microorganisms inside a BCR include aerobic, anaerobic and facultative bacteria, fungi, and protozoa.","BCR 110 is preferably designed to contain many different types of microorganisms, each of which is ideally suited to remove at least one type of organic matter from wastewater.","By way of example, BCR 110 uses heterotrophic bacteria (e.g., Achromobacter, Alcaligenes, Arthrobacter, Cirtomonas, Flavobacterium, Pseudomonas, and Zoogloea) for removal of BOD.","BOD is created by any matter containing a carbon molecule normally present in wastewater and that is generated from any one of human waste, food waste, animal waste, and plant waste.","Blower 204 is effective in providing oxygen to microorganisms in wastewater.","Size of bubbles formed in wastewater from pumping air and the amount of air pumped dictate the amount of oxygen dissolved in wastewater.","Those skilled in the art will recognize that small bubbles may be twice as efficient at transferring oxygen because they provide greater surface area of air per mass of air.","Bubbles also mix wastewater inside the BCR to ensure that nutrients in wastewater are in constant contact with the bacteria that consumes them.","The presence of biological chips provides a high surface area inside the reactor to which the microorganisms may affix.","By way of example, the ratio of surface area inside the BCR to volume of BCR is between about 32 square feet per cubic foot and about 130 square feet per cubic foot.","Preferably, however, the ratio of surface area inside the BCR to volume of BCR is about 73.5 square feet per cubic feet.","High surface area combined with high oxygen concentration aide the metabolic rates of microorganisms.","The affixed microorganisms quickly remove all available food in the form of organic particulate matter (which contribute to BOD) from the reactor and leave a situation of high metabolic rates and low amounts of food (i.e., there is a low ratio of food to microorganism).","Over a period of time, most solids in the reactors continue to be active and remove more BOD from the influent water.","Eventually, as more and more of the food is depleted inside the reactor, the microorganisms die from starvation.","BCR 112 is preferably designed to contain at least one type of microorganism, which removes at least one type of organic matter that is particularly difficult to remove from the wastewater in BCR 110 or requires additional processing time, i.e., above and beyond the processing time in BCR 110.According to the present teachings, it is also possible to have additional BCRs, in addition to BCRs 110 and 112, to facilitate effective organic matter removal.","By way of example, an initial step of nitrification is carried out in BCR 112 by autotropic bacteria Nitrosomonas, which converts ammonia to nitrite, despite the fact that some nitrifying bacteria exist in BCR 110.A third BCR (not shown in FIG.","1A to simplify illustration) may be used for a subsequent step of nitrification using autotropic bacteria Nitrobacter.","In preferred embodiments of the present teachings, BCRs 110 and 112 are about 7 feet long, 10.5 feet wide, and 8 inches in height.","Temperature inside BCRs is preferably between about 15° C. and about 33° C., and the hydraulic residence time is preferably about 8 hours.","According to one embodiment of the present teachings, BCRs are about 40% filled with small biorings, have 133 cubic feet per minute of diffused air flowing through it during operation, and use 6 ounces of defoaming agent per day.","In cold climates, where heat dissipation is relatively high, it is preferable to keep substrate levels high to carry out nitrification effectively.","The term “high substrate levels” means keeping a certain level of biological matter (sludge) inside the BCR to maintain its thermal mass and avoid wide temperature swings inside the BCR and/or also means keeping the bacteria count high to accommodate the greater die-off rate when temperatures drop.","The present teachings use of a BCR, individually or in combination with other BCRs, represent an active process because it is provides air and constantly places bacteria in contact with nutrients through circulation of wastewater to effectively encourage nutrient uptake.","Furthermore, the surface area inside the BCR is also optimized for removal of organic waste.","Aerobic sludge digester 114 is one type of BCR, except that it is designed to remove sludge.","In other words, digester 114 contains microorganisms that are known to consume, and therefore remove, sludge.","Although the BCRs and aerobic sludge digesters remove organic matter and lower the BOD, they leave wastewater rich with nitrates from the endogenous decay of microorganisms that have run out of food source.","To this end, previously described DAF tank 106 and a second SRT, shown as SRT 116 in FIG.","1A, are used to remove dead microorganisms.","To remove dead microorganisms, DAF tank 106 is provided with another chamber, separate from the chamber which is used to remove from wastewater solids that are not dead microorganisms.","IIRAP 118 is used in system 100 to remove nutrients from wastewater.","FIG.","3 shows HRAP 300, according to one preferred embodiment of the present teachings.","HRAP 300 includes a tank 302 containing algae 308.A spectrum of radiation 306 operates at wavelengths that range from about 102 nm and 106 nm.","This spectrum of radiation is preferably disposed at a location that is between about ⅓ and about ½ the depth of HRAP 300.At the bottom of tank 302, a solid waste layer 304 accumulates which may ultimately be removed.","A hydraulic pump and a paddle (both not shown to simplify illustration) are preferably provided in HRAP 300 for stirring and aeration of wastewater.","Aeration and stirring facilitates driving up the dissolved oxygen level in wastewater to promote algae growth.","Tank 302 is preferably maintained at a temperature that is between about 21° C. and 35° C. FIG.","4 shows a perspective view of HRAP 300, in accordance with one preferred embodiment of the present teachings.","Inside HRAP 300 wastewater is preferably guided through a channel, which allows the water to traverse back and forth along a length of tank 302.The channel carves out a hydraulic path for wastewater and is preferably serpentine in shape.","HRAP may have any dimensions that effectively remove nutrients from wastewater.","The present teachings recognize, however, that nutrient load and flow rate of wastewater drive HRAP dimensions.","By way of example, HRAP has a length of about 24 feet, a width of about 77 feet, and a height of about 4 feet.","IIRAP preferably provides a surface area that is between about 1000 square feet and about 50,000 square feet and, more preferably, about 1848 square feet for wastewater treatment.","The channel length is preferably between about 200 feet and about 3000 feet.","Inside the channel of HRAP, wastewater moves at a velocity of 10 inches per second and has a residence time of about 72 hours.","HRAP primarily uses algae to remove nitrates and phosphates from wastewater.","Growth rate of algae is dictated by available oxygen, temperature, light, and nutrients.","Conventional algal ponds are very shallow because they facilitate introduction of oxygen and penetration of light to promote algae growth.","Unfortunately, for processing relatively large volumes of wastewater, conventional algal ponds are very large, i.e., they are typically measured in hectares.","The present teachings preferably use an HRAP, which is deeper and not so spread out.","In preferred embodiments of the present teachings, it both aerates and stirs wastewater to effectively introduce oxygen.","Furthermore, a radiation source inside the HRAP effectively facilitates penetration of light through greater depths of wastewater.","As a result, HRAPs according to the present teachings may occupy as little as 160 square meters for 120-cubic-meters-per-day flow systems.","Preferably contemporaneous with above-described treatment of wastewater, the present teachings also treat byproducts resulting from wastewater treatment.","To this end, FIG.","1B shows a system 140, according to one embodiment of the present teachings, for separating methane gas from other components of biogas that are produced after anaerobic digestion in wastewater.","Although this system and other such systems which process byproducts of wastewater treatment may function either in a contemporaneous or non-contemporaneous manner relative to wastewater treatment, in preferred embodiments, inventive systems and methods process the byproducts in a contemporaneous manner to increase throughput and avoid byproduct build-up.","System 140 includes a tank 126, preferably a scrubber, for removal of methane 132 so that it may subsequently be used as energy source (described below with reference to FIG.","5).","Tank 126 includes a first inlet for receiving a stream of water (e.g., a portion of treated water 125 from maturation pond 122 of FIG.","1A), a first outlet for dispensing an effluent water stream 130 having dissolved therein certain components of biogas, a second inlet for receiving biogas 128 produced after anaerobic digestion, and a second outlet for methane exhaust 132.As shown in FIG.","1A, methane, one component of biogas, is a residual gas as it is not soluble in water.","Tank 126 may receive a water stream from any source of water or pure water.","In the interest of water conservation, the present teachings recognize that a portion of treated wastewater resulting from wastewater treatment may be used for processing byproducts of wastewater treatment.","Tank 126 preferably comes equipped with a bubbler 129 to produce bubbles.","Specifically, bubbler 129 introduces biogas 128 inside a tank full of water in the form of micro-bubbles.","The bubbles provide a large surface area between the biogas/water interface to facilitate dissolving certain soluble biogas components in water.","Residual methane gas exits tank 126 and is further processed as described below in system 170 of FIG.","5.FIG.","5 shows a system 170, according to one embodiment of the present teachings, for converting methane exhaust into electricity and for converting residual gases resulting from an electricity generator to a simpler, less complicated molecular form that may be used by HRAP 118 of FIG.","1A to foster growth of algae, which is useful for producing, among other things, biofuels.","System 170 includes an electrical generator 150 and a tank 160, which is preferably a scrubber.","Electrical generator 150 uses methane exhaust 132 (generated inside tank 126 of FIG.","1B) to generate electricity and a produce a gaseous mixture 152 (e.g., including at least one of CO2, SOx, and NOx), which are fed into a tank 160.According to FIG.","5, a portion of treated water 125 from maturation pond 122 of FIG.","1A enters tank 160 such that it contacts gaseous mixture 152 of tank 160.A bubbler 156, similar to bubbler 129 of FIG.","1B, ensures that the gaseous mixture in the form of micro bubbles contacts water to facilitate dissolving components of the gaseous mixture in water.","As a result, a certain amount of the gaseous components of mixture 152 dissolves in the treated water to form water 162 that is enriched with aqueous components (i.e., predominantly at least one of CO2, SOx, and NOx).","As shown in FIG.","5, this gas-enriched water stream 162 is advanced to HRAP 118 of FIG.","1A, where algae production is promoted by the dissolved gaseous components in water.","The residual gases, which include remaining amounts of at least one of CO2, SOx, and NOx that did not dissolve in treated water, are recycled back to tank 160 via line 154 for further treatment.","The goal of the recycling feature of FIG.","1B is to ultimately dissolve all of CO2, SOx, and/or NOx gases in water and advance these gases to HRAP 118 of FIG.","1A to promote algae growth.","FIG.","1C shows a system 180, according to one embodiment of the present teachings, for processing gas (i.e., predominantly ammonia gas and sulfur gas) produced by BCR 110 of FIG.","1A.","According to this figure, gaseous byproducts resulting from aerobic digestion of wastewater that is carried out in BCR 110, are transported to a tank 140, preferably a scrubber, for processing.","Like tank 160 of FIG.","5 and tank 126 of FIG.","1A, tank 140 of FIG.","1C comes equipped with bubbler 139, which introduces the gas produced in BCR 110 in the form of micro bubbles through the tank full of treated water to facilitate dissolving in water of those components of the gaseous byproducts that are soluble in water.","Tank 160 includes a first inlet for receiving water and a first outlet for dispensing water, which is enriched with at least a soluble amount of gaseous components that dissolve.","In preferred embodiments of the present teachings, the water is treated water 125 from maturation pond 122 of FIG.","1A.","However, it is possible to so treat the gaseous byproducts with a water stream obtained from any source.","Tank 140 has a second inlet for receiving gas from BCR 110 and a second outlet for dispensing the residual gas that does not dissolve in water.","An ammonia concentration sensor 182 is located downstream from tank 140 and is capable of controlling the flow of effluent stream from tank 140 to either HRAP 118 or back to BCR 110.To this end, ammonia sensor 182 is communicatively coupled to two different valve assemblies 184 and 186 via control lines 188 and 190, respectively.","When ammonia concentration sensor 182 detects ammonia concentration in the effluent stream of tank 140 to be either equal to or greater than a predetermined concentration value, sensor 182 activates valve assembly 184 to convey an effluent stream of tank 140 to BCR 110 for further treatment.","In the alternative, when sensor 182 detects ammonia concentration in the effluent stream to be less than the predetermined concentration value, sensor 182 activates valve assembly 186 to convey the effluent stream to HRAP 118.In preferred embodiments of the present teachings, the value of predetermined ammonia concentration lies in a range that is between about 0 ppm and about 10 ppm, depending primarily on the concentration of ammonia in a feed stream that is being reduced by oxidation, e.g., in the BCR reactor.","An effluent stream with low ammonia concentration suggests nitrogen is present in the effluent stream in a less complex form which is useful for promoting algae growth in HRAP 118.In contrast, a high ammonia concentration suggests that the effluent stream does not have sufficient amount of nitrogen in simple form to facilitate algae growth in HRAP 118.Those skilled in the art will recognize that although system 180 is shown in connection with BCR 110, a similar system could be used to process the gas emanating in BCR 112 of FIG.","1A.","Regardless of whether gas emanating from BCR 110 or BCR 112 is processed as described above, if the concentration of ammonia in the effluent stream of a scrubber, for example, is greater than or equal to a predetermined concentration value, then that effluent stream is sent hack to the BCR so that the dissolved aqueous ammonia in the effluent stream may be broken down to a simpler form which is ultimately useful to promote algae growth in HRAP 118.Similar to ammonia gas, sulfur is another gaseous byproduct of aerobic digestion carried out in BCR 110 or BCR 112 of FIG.","1A.","Instead of or in addition to using an ammonia concentration sensor, system 180 of FIG.","1C may include a sensor for detecting the concentration of sulfur gas (not shown to simplify illustration) if the presence of sulfur gas is expected or suspected as a byproduct of aerobic digestion.","Those skilled in the art will recognize that the valve assemblies, similar to those shown in connection with the ammonia concentration sensor, may be used in conjunction with the sulfur concentration sensor.","Because sulfur naturally dissipates faster relative to ammonia, it is not necessary in preferred embodiments of the present teachings to monitor the sulfur concentration in the same way as the ammonia concentration.","In even more preferred embodiments of the present teachings, only the ammonia concentration is measured and so long as that concentration is less than a predetermined value, it is safe to assume that the sulfur concentration is also sufficiently low to advance the effluent stream from tank 140 to HRAP 118.In preferred embodiments of the present teachings, electrical generator 150 is commercially available from General Electric, Inc.'s Jenbacher gas engine division located in Jenbach, Austria.","However, other electrical generators, which use methane to generate electricity will work also.","In preferred embodiments of the present teachings, tank 126 (in system 140 of FIG.","1B), tank 140 (in system 180 of FIG.","1C), and tank 160 (system 170 of FIG.","5) are large enough to hold at least a volume of liquid that is between about 380 liters and about 38000 liters.","Wastewater treatment according to present teachings has many advantages over the conventional wastewater treatment technology.","At a minimum, conventional wastewater treatment processes release noxious byproducts of anaerobic and aerobic digestion into the atmosphere, some of which are believed to contribute to the greenhouse effect.","In sharp contrast, the present teachings offer novel systems and methods to process these byproducts to generate clean energy and promote production of useful downstream products.","In preferred embodiments of the novel systems and methods of the present teachings, a portion of the treated wastewater is used to process the byproducts as mentioned above.","It is counter to conventional wisdom that treated or purified water obtained from wastewater treatment should be used to treat environmentally harmful byproducts because after putting a substantial amount of energy in treating wastewater, conventional wastewater techniques teach away from wasting that energy by contaminating that treated water.","As a result, conventional wastewater treatment processes fail to recognize, among other things, that a portion of the treated water may be used to convert byproducts of wastewater treatment into clean energy.","The present teachings provide a substantially closed system that treats wastewater and recycles a portion of that treated wastewater to convert noxious byproducts of wastewater treatment into useful energy.","By way of example, if the closed system is implemented on a farm, then the wastewater generated at the farm may be treated and at the same time be used to produce clean energy for the farm.","In other respects unrelated to treatment of byproducts, at a minimum, conventional wastewater treatment processes fail to recognize: (i) that decomposition of organic matter depletes soluble oxygen in wastewater constantly during various treatment steps; (ii) the need to substantially maintain the level of dissolved oxygen in wastewater at various stages is important for effective treatment; and (iii) that failure to substantially maintain level of dissolved oxygen and lower solid content through each stage of wastewater treatment causes a reversible reaction which reverses the treatment accomplished in previous treatment steps.","To this end, various steps in preferred embodiments of the present teachings recognize the need to drive down BOD, solid content, and nutrient level and maintain or increase level of dissolved oxygen in wastewater.","In preferred embodiments of the present teachings, wastewater undergoes different types of treatment.","By way of example, BOD-creating solids are removed first.","Then, the bacteria consume the organic matter.","Next, nutrients present in wastewater are removed.","After performing a first type of treatment, however, the present teachings recognize the need to stabilize the wastewater before advancing it to a second type of treatment.","Stabilizing involves preventing a meaningful change in certain important properties of wastewater, e.g., ROD level, dissolved oxygen level, solid content level, and nutrient level, which are susceptible to changing to undesired values by a reversible reaction.","Specifically, by lowering BOD levels and solid content and increasing or substantially maintaining dissolved oxygen levels in wastewater throughout the various stages, the present teachings effectively transition from one treatment type to another, without suffering from drawbacks of a reversible reaction.","In accordance with one embodiment, the inventive process using system 100 of FIG.","1A may begin when a treatment system 100 receives wastewater for treatment directly from an anaerobic tank (e.g., anaerobic tank 102 of FIG.","1A).","Inside anaerobic tank 102, complex organic material is broken down into smaller constituent organic material by anaerobic bacteria under anaerobic conditions.","By way of example, inside anaerobic tank 102, a temperature may be a value that is between about 30° C. and 40° C., a pressure that is about 1 atmosphere, and a volume that is between about 10 gallons per minute and about 15,000 gallons per minute.","The volume of the tank is completely scalable and may be higher than 15,000 gallons per minute so long as the necessary amount of equipment is used to process a large amount of liquid in parallel.","In the anaerobic tank, the wastewater is treated with microorganisms that carry out anaerobic digestion, causing the release of biogas 128 that is captured atop an anaerobic tank and delivered to a tank (e.g., tank 126 of FIG.","1B), which is preferably a scrubber and is capable of separating methane from the other components of biogas.","The wastewater is then immediately advanced for solid removal as one type of treatment.","In a preferred embodiment of the present teachings, solid removal is carried out methodically in different steps.","It is noteworthy that in this embodiment, not only are solids removed at different steps, but the inventive process is designed to substantially maintain the level of dissolved oxygen in wastewater during these steps to avoid a reversible reaction.","Solid removal preferably begins with removal of relatively large solids from wastewater using a mechanical technique.","By way of example, a solids separator such as the one shown in FIG.","1A is preferably used for pressing wastewater containing solids because it also introduces air into the wastewater during the pressing action.","As a result, pressing not only removes large solids from wastewater but also maintains the level of dissolved oxygen in wastewater.","At this early stage of solid removal, an aerobic process ensures a natural biological degradation and purification process in which bacteria that thrive in oxygen-rich environment break down and digest the organic matter.","Maintaining oxygen levels during solid removal ensures that such bacteria do not die off and that level of BOD-contributing solids and solid content in wastewater does not increase.","Undesired increase in BOD-contributing solids at this stage would defeat the ultimate purpose of removing the BOD-contributing solids in this step.","In other words, during a single treatment step, lowering solid content, lowering BOD level, and substantially maintaining or increasing level of dissolved oxygen in wastewater prevents a reversible reaction that increases BOD, solid content, and/or lowers level of dissolved oxygen in wastewater.","After removing large solids, preferred embodiments of the present teachings focus on the removal of medium-sized particles using small air bubbles.","In this treatment step, medium-sized.","solids are carried by an upward motion of air bubbles and removed as explained previously.","As a result, bubbles remove BOD-contributing solids, lower solid content, and introduce oxygen simultaneously to substantially maintain or increase a level of dissolved oxygen in wastewater.","The advantages of lowering BOD and solid content, and at the same time substantially maintaining or increasing a level of dissolved oxygen in wastewater realized in the previous step, are also realized in this step.","For removal of finer solids from wastewater, the inventive process in a preferred embodiment moves to a tank, such as SRT 108 as shown in FIG.","1A.","This tank also stabilizes the wastewater before removal of organic matter commences.","Specifically, the tank is designed to remove fine solid particles using a screen when diffused airflow is used inside the tank.","Such air flow provides cleaning action to remove the solid build up on the screen and introduces oxygen into wastewater.","The advantages of lowering BOD and solid content in wastewater, and at the same time substantially maintaining or increasing level of dissolved oxygen in wastewater realized in the previous steps, are also realized in this step.","Next, the inventive process preferably moves to removal of organic matter as another type of treatment.","In this stage of treatment, preferably in a BCR, such as the one shown in FIG.","1A, microorganisms in the presence of biological chips consume organic matter.","The microorganisms release gas containing ammonia and sulfur.","Various steps of the present teachings (described below with reference to FIG.","1C) provide a means to clean this gas with recycled wastewater 125.Consumption of organic matter by microorganisms is enhanced by the presence of a blower, which introduces oxygen into wastewater, increasing level of dissolved oxygen in wastewater.","With removal of organic matter, wastewater has lower BOD level and solid content and increased level of dissolved oxygen.","Microorganisms after consuming a substantial amount of organic material, however, die off and increase both BOD level and solid content.","If the dead microorganisms are not timely removed, level of dissolved oxygen in wastewater will drop and a reversible reaction will increase BOD level and solid content in wastewater.","As a result, in the next treatment step, the present teachings offer provisions to remove dead microorganisms from wastewater.","To this end, preferably, first anaerobic treatment and then an aerobic treatment is used.","It is noteworthy that in preferred embodiments of the present teachings, wastewater at this stage is subjected to anaerobic digestion for a second time.","In the anaerobic treatment at this stage, preferably an SRT is sealed off to make sure that all aerobic microorganisms die off.","At the same time, using screens inside the SRT, dead microorganisms are removed using screens inside the SRT.","This lowers both BOD level and solid content in wastewater.","But, before wastewater may advance to the next stage, the present teachings realize that level of dissolved oxygen in wastewater should increase.","In the next step, aerobic treatment is preferably carried out using a DAF tank such as the one shown in FIG.","1A.","Diffused airflow inside the DAF tank raises level of dissolved oxygen and removes residual solids.","Now, wastewater having lower BOD level and solid content and higher level of dissolved oxygen is ready for the next stage of treatment.","In the next stage, wastewater is treated in algal pond, preferably an HRAP such as the one shown in FIG.","1A, to effectively remove nutrients from wastewater.","Nutrient removal from wastewater is carried out by algae, which in the presence of an operating radiation source effectively consumes nutrients.","Algae also boost level of dissolved oxygen in wastewater.","However, level of dissolved oxygen in wastewater may not be high enough to meet the requirement of discharge to environment.","It is important to recognize that if after anaerobic treatment aerobic treatment did not follow, then wastewater with high concentration of ammonia, as opposed to nitrates or nitrogen, would have entered the HRAP posing a risk of killing algae.","Thus, anaerobic treatment followed by aerobic treatment ensures that wastewater is prepared for nutrient removal in the subsequent steps.","In the next treatment steps, dissolved oxygen level in wastewater is raised to allow discharge to environment.","Preferably a DAF tank is used to provide diffused air flow for raising level of dissolved oxygen and removing algae and other solids from wastewater.","Solid removal lowers BOD level and solid content in wastewater.","Then, for removal of finer particles, wastewater is advanced to an SRT, which uses diffused air for removal of solids from and introduction of oxygen to wastewater.","Consequently, wastewater has the requisite high level of dissolved oxygen, lower BOD level, and solid content for discharge into environment.","Although wastewater is now ready for discharge into environment, preferred embodiments treat this wastewater in a maturation pond where it is exposed to elements found in the environment.","Wastewater matures and is adapted to the natural environment in the maturation pond, from where it is discharged to the environment.","As shown in FIG.","1A, solids removal is carried out at least partially in DAF tank 106 and SRT 108.During such solids removal, however, aerobic bacteria are typically present.","As a result, when oxygen is added to these tanks during solids removal, these tanks are not only efficiently removing solids, but are effectively carrying out aerobic digestion on the wastewater well before that wastewater reaches the BCR reactors, where the wastewater further undergoes aerobic digestion.","In accordance with preferred embodiments, the inventive processes on a parallel track treat the gaseous byproducts produced during wastewater treatment.","By way of example, biogas (e.g., methane, carbon dioxide, ammonia, hydrogen, and sulfur) resulting from anaerobic digestion is delivered from an anaerobic tank to another tank, which is preferably a scrubber.","Before biogas is conveyed to the tank, the tank is filled with water, which is preferably treated water obtained after the conclusion of a wastewater treatment process.","Inside the tank, water contacts the biogas.","In preferred embodiments of the present teachings, biogas is in the form of tiny micro bubbles when it contacts water.","Biogas in bubble form provides a high surface area between the biogas/water interface to allow certain gases in the biogas mixture to dissolve in water.","However, as methane does not dissolve in water, it exhausts from the tank.","Instead of releasing methane exhaust into the atmosphere, as conventional processes do, the present teachings deliver methane for further processing to an electrical generator located downstream.","From inside the tank, a stream of water, which contains certain biogas components dissolved therein, is discharged to a tank for solids removal (e.g., DAF tank 106 of FIG.","1A).","The methane exhaust is further processed (e.g., in system 170 of FIG.","5) to produce electricity and other useful products.","Specifically, methane gas is delivered to an electrical generator, which converts methane to electricity and produces other byproduct gases (e.g., at least one of CO2, SOx, and NOx).","These gaseous byproducts are next conveyed to a tank, preferably a scrubber, where they are treated substantially similarly to the treatment of biogas as a byproduct (i.e., tiny micro bubbles of the gaseous mixture are conveyed through water to dissolve those components of the gaseous mixture which dissolve in water).","Preferably, treated water is used to process the byproduct gas.","Residual gas not dissolved in water is recirculated back to the tank for further processing i.e., multiple passes may be made through the tank to dissolve the residual gases in water.","Water effluent that includes the dissolved gases is conveyed to an algal pond (e.g., HRAP 118 of FIG.","1A) to promote algae growth.","With regard to the energy produced by the electrical generator, the amount of energy is significant.","By way of example, for a farm that raises dairy cattle, an electrical generator produces between about 1 and about 5 kilowatts of electricity per day per animal.","Processing of wastewater by aerobic digestion also produces byproducts, which are treated according to the preferred embodiments of novel systems and methods of the present teachings.","In accordance with one preferred embodiment, the inventive processes may begin when byproduct gas is received into a tank, preferably a scrubber, after wastewater has undergone aerobic digestion (e.g., in BCRs 110 and 112).","Byproduct gas (e.g., shown denoted by reference numeral 142 of FIG.","1C) of aerobic digestion includes at least one of ammonia gas and sulfur gas.","Before the byproduct gas is received, however, the tank is filled with water, which is preferably treated wastewater.","In preferred embodiments, byproduct gas processed according to the present teachings is introduced in bubble form.","A certain amount that is soluble of certain components of the byproduct gas dissolve in water and the remaining, undissolved amounts or components, such as residual ammonia gas or residual sulfur gas, are recycled back to the tank further processing (i.e., for further attempts to dissolve the residual ammonia gas and sulfur gas in water in subsequent contact cycles in the tank).","The resulting effluent stream enriched with the soluble byproduct gas components is discharged from the tank and processed depending on the concentration of aqueous ammonia and sulfur in the water stream.","Using an ammonia concentration sensor, the concentration of ammonia in the wastewater is determined.","If the effluent contains ammonia in a concentration that is greater or equal to a predetermined concentration value, then the ammonia is typically sent back to the BCR reactor, from where the byproduct gas had originated.","In this BCR, the residual ammonia gas undergoes further processing so that it is reduced to simpler molecular forms, such as nitrates, nitrites, or nitrogen, which are useful for algae growth (e.g., in HRAP 118 of FIG.","1A).","If, however, the concentration of ammonia is sufficiently low, i.e., below the predetermined concentration value, then the effluent stream is considered to have simpler forms of nitrogen which are useful for algae growth.","Accordingly, effluent streams with such low concentrations of ammonia are advanced to an algal pond (e.g., in HRAP 118 of FIG.","1A).","In other preferred embodiments of the present teachings, the concentration of sulfur is similarly discerned.","If the sulfur concentration sensor detects the concentration of sulfur gas to be greater than or equal to a predetermined concentration value, then the effluent stream is returned back to the BCR reactor, from where the byproduct gas had originated.","In this BCR, the residual sulfur gas undergoes further processing so that it is consumed if not in the first pass back to the BCR, then in the subsequent ones.","Alternatively, if the sulfur concentration detects the concentration of sulfur gas to be less than the predetermined concentration value, then the effluent stream advances to the algal pond.","In light of the above disclosure, those skilled in the art will recognize that in preferred embodiments of the present teachings, the effluent stream of the tank (e.g., a scrubber) are only advanced to an algal pond when both concentration of aqueous ammonia and sulfur gas are below their respective predetermined concentration values.","However, compared to ammonia, sulfur is known to dissipate relatively quickly and, therefore, in preferred embodiments of the present teachings, only the concentration of ammonia in the effluent stream is monitored as described above.","FIG.","6 shows a system 600, according to one preferred present arrangement, for converting solid byproducts of wastewater treatment into a plant life enhancing product, e.g., fertilizer, biocide, pesticide, and/or agricultural feed.","System 600 includes an anaerobic feed tank 602, a solids separator 604, a DAF tank 606, an SRT #1 608, a BCR #1 610, a BCR #2 612, an aerobic sludge digester 614, an SRT #2 616, an HRAP 618, and an SRT #3 620, each of which is substantially similar to their counterparts, anaerobic feed tank 102, solids separator 104, DAF 106, SRT #1 108, BCR #1 110, BCR #2 112, aerobic sludge digester 114, SRT #2 116, HRAP 118, and SRT #3 120, respectively, in system 100 of FIG.","1A.","System 600 further includes an intermediate blender 660, that receives and blends different types of solid byproducts of wastewater treatment, i.e., anaerobically activated coarse solids 650, anaerobically activated medium-sized solids 624, and/or anaerobically activated fine solids 652, produced from solids separator 604, DAF tank 606, and SRT #1 608, respectively, to form an anaerobically activated organic residue 662.Preferably, these various-sized solids primarily include fibrous, cellular material (e.g., lignin, cellulose, hemicellulose) that is broken down in the above-mentioned components.","System 600 further includes a blender 664 that receives and mixes anaerobically activated organic residue 662 from blender 664 with one or more of other solid byproducts of wastewater treatment, i.e., aerobically activated organic residue 627, dead microorganisms 654, algae-enriched slurry 656, and/or algae 658, from aerobic sludge digester 614, SRT #2 616, HRAP 618, and SRT #3, respectively, to form a slurry 666.The present arrangement also optionally includes a dryer 668 capable of drying slurry 666, and a pelletizer 670 capable of pelletizing the dried product received from dryer 668.Anaerobic feed tank 602 is designed to receive wastewater, which includes agricultural residue (e.g., biomass and manure), and treats the wastewater under anaerobic conditions.","Inside anaerobic feed tank 602, among other things, complex organic material from agricultural residue is digested into smaller constituent organic material by anaerobic bacteria.","Anaerobic feed tank 602 then delivers the resulting anaerobically activated slurry 632 to solids separator 604 for further treatment.","Solids separator 604 separates anaerobically activated coarse solids 650 from anaerobically activated slurry 632, using mechanical techniques, to form an anaerobically activated slurry depleted of coarse solids 634.Anaerobically activated coarse solids 650 have an average particle size that is greater than about 150 pm.","As shown in FIG.","6, once separated from treated wastewater, anaerobically activated coarse solids 650 are delivered to intermediate blender 660 for blending with other types of solid byproducts.","Also as shown in FIG.","6, anaerobically activated slurry depleted of coarse solids 634 is then delivered to DAF tank 606 for further treatment.","DAF tank 606 separates anaerobically activated medium-sized solids 624 from anaerobically activated slurry depleted of coarse solids 634 to form an anaerobically activated slurry depleted of medium-sized solids 636.To facilitate their removal, anaerobically activated medium-sized solids 624 are carried by an upward motion of air bubbles introduced into DAF tank 606.DAF tank 606 removes medium-sized solids from wastewater, which have an average particle size that ranges from about 25 μm to about 150 μm.","According to FIG.","6, separated, anaerobically activated medium-sized solids 624 are delivered to intermediate blender 660 for blending with other types of solid byproducts.","Also, as shown in FIG.","6, anaerobically activated slurry depleted of medium-sized solids 636 is then delivered to SRT #1 608 for further treatment.","SRT #1 608 separates anaerobically activated fine solids 652 from anaerobically activated slurry depleted of medium-sized solids 636 to form anaerobically activated slurry depleted of solids 638.Removal of anaerobically activated fine solids 652 is facilitated by use of a screen when diffused air flow is introduced inside the tank.","SRT #1 601 removes solids that have an average particle size that is less than about 25 μm.","According to FIG.","6, anaerobically activated fine solids 652 are delivered to intermediate blender 660 for blending with other types of solid byproduct.","Also, as shown in FIG.","6, the resulting anaerobically activated slurry depleted of solids 638 is then delivered to BCR #1 610 for further treatment.","Intermediate blender 660 receives and blends one or more of anaerobically activated coarse solids 650, anaerobically activated medium-sized solids 624, and anaerobically activated fine solids 652, to form anaerobically activated organic residue 662.Preferably, intermediate blender 660 is designed to blend relatively fibrous solid byproducts of wastewater treatment (e.g., lignin, cellulose, and hemicellulose).","As shown in the embodiment of FIG.","6, intermediate blender 660 delivers anaerobically activated organic residue 662 to blender 664 for blending with other solid byproducts of wastewater treatment.","In alternate embodiments of the present arrangement, however, a single blender is configured to blend all solid byproducts of wastewater treatment.","BCR #1 610 treats organic matter from anaerobically activated slurry depleted of solids 638, which are typically enriched with nutrients, by aerobic digestion.","Preferably, anaerobically activated slurry depleted of solids 638 are treated with at least one type of microorganism, which consumes organic matter.","In one preferred embodiment of the present arrangement, the resulting wastewater slurry 640 treated in BCR #1 610 is delivered to BCR #2 612 for further treatment with one or more microorganisms that preferably consume organic matter that is particularly difficult to remove.","The wastewater slurry 642 resulting from treatment in BCR #2 is delivered to aerobic sludge digester 614 for further treatment under aerobic conditions with one or more microorganisms that are known to consume solid sludge, i.e., accumulated organic matter, producing aerobically activated organic residue 627.Preferably, the microorganisms include at least one microorganism that converts ammonia to nitrites and at least one microorganism that converts nitrites to nitrates.","Aerobically activated organic residue 627 is separated from treated wastewater slurry 642, producing aerobically activated slurry 644, which is in a nutrient-enriched state.","As shown in FIG.","6, aerobically activated organic residue 627 is then delivered to blender 664 for blending with other solid byproducts of wastewater treatment.","Also as shown in FIG.","6, aerobically activated slurry 644 is then delivered to SRT #2 616 for further treatment.","Though the embodiment of FIG.","6 shows two BCRs and one aerobic sludge digester, alternate embodiments of the present arrangement include any number of BCRs and aerobic sludge digesters.","Likewise, other embodiments of the present arrangement include no BCRs or no aerobic sludge digesters.","SRT #2 616 is sealed off to create anaerobic conditions during treatment of aerobically activated slurry 644, which kills substantially all of the aerobic microorganisms utilized in BCR #1 610, BCR #2 612, and aerobic sludge digester 614.Dead microorganisms 654 are then removed, preferably using screens inside SRT #2 616.As shown in FIG.","6, dead microorganisms 654 are next delivered to blender 664 for blending with other solid byproducts of wastewater treatment.","Also as shown in FIG.","6, the resulting nutrient-enriched slurry 646 is delivered to HRAP 618 for further treatment.","In preferred embodiments of the present teachings, however, nutrient-enriched slurry 646 is first delivered to DAF tank 606 for further aerobic treatment, as described above with reference to FIG.","1A, and then delivered to HRAP 618 for further treatment.","In HRAP 618, algae-enriched slurry 656 is separated from nutrient-enriched slurry 646 to form a nutrient-depleted slurry 648.Algae-enriched slurry 656 is delivered to blender 664 for blending with other solid waste products of wastewater treatment.","In certain embodiments of the present arrangement, nutrient-depleted slurry 620 is delivered to SRT #3 620 for further treatment.","In preferred embodiments, however, nutrient-depleted slurry 620 if first delivered to DAF tank 606 for further aerobic treatment, as described above with reference to FIG.","1A, and then delivered to SRT #3 620 for further treatment.","In SRT No.","3 620, algae 658 are separated from nutrient-depleted slurry 648.Algae 658 are then delivered to blender 664 for blending with other solid waste products of wastewater treatment.","Algae 658, which are rich in nutrients (e.g., nitrogen, phosphorous, and potassium), provides nutrients for use in fertilizer, biocide, pesticide, and/or agricultural feed.","Blender 664 is any blender capable of blending solid waste products of wastewater treatment.","Preferably, blender 664 is designed to blend relatively small products of wastewater treatment (e.g., anaerobically activated organic residue 662, aerobically activated organic residue 627, dead bacteria 654, algae-enriched slurry 656, and algae 658) to produce slurry 666.Though the embodiment of FIG.","6 includes intermediate blender 660 and blender 664, alternate embodiments of the present arrangement include one blender that is configured to blend all solid byproducts of wastewater treatment.","Regardless of whether a single or multiple blenders are used, the present teachings contemplate the use of an external amendment that provides additional amounts of a desired material (e.g., sulfur and nitrogen) so that a predetermined concentration of the desired material is reached in the plant life enhancing composition.","To this end, FIG.","6 shows that, in one embodiment of the present teachings, an external amendment 674 is connected to intermediate blender 660 via a connection 676 and is also connected to a blender 664 via a connection 678.Although it is not necessary to include the external amendment feature and its associated connections, in those instances where the concentration of a desired material needs to be supplemented in the plant life enhancing composition, external amendment 674 and at least one of the associated connections represent a preferred embodiment of the present teachings.","Slurry 666 is comprised of one or more of anaerobically activated organic residue 662, aerobically activated organic 627, dead bacteria 654, algae-enriched slurry 656, and algae 658.Slurry 666 may be used to produce a plant life enhancing composition, e.g., fertilizer, pesticide, biocide, and/or agricultural feed, though in alternate embodiments of the present arrangement, slurry 666 may optionally be delivered to dryer 668 for drying.","Dryer 668 is any dryer capable of drying slurry 666.The dried product resulting from dryer 668 may be used as fertilizer, pesticide, biocide, and/or agricultural feed.","Optionally, however, the dried product may instead be delivered to pelletizer 670 for pelletizing.","Pelletizer 670 is any pelletizer capable of pelletizing the dried product of dryer 668.In one preferred arrangement, the pellets resulting from pelletizer are used as a plant life enhancing composition, e.g., fertilizer, pesticide, biocide, and/or agricultural feed.","FIG.","7 shows a process 700, according to one preferred arrangement, for converting solid byproducts of wastewater treatment into a plant life enhancing product, e.g., fertilizer, biocide, pesticide, and/or agricultural feed.","Process 700 begins with a first step 702, which includes anaerobically digesting agricultural residue to produce anaerobically activated organic residue and ammonia-enriched water.","According to one preferred arrangement, anaerobically digesting agricultural residue to produce an anaerobically activated organic residue and an ammonia-enriched water is carried out using a series of components (e.g., anaerobic feed tank 602, solids separator 604, DAF tank 606, and SRT #1 608 of FIG.","6) that treat organic residue under anaerobic conditions and remove various-sized solid byproducts of wastewater treatment (e.g., anaerobically activated coarse solids 650, anaerobically activated medium-sized solids 624, and/or anaerobically activated fine solids 652 of FIG.","6) from wastewater.","The resulting wastewater is ammonia-enriched and delivered for further treatment.","Though not shown in FIG.","7, prior to step 704, anaerobically activated organic waste, which is comprised of one or more of coarse, medium-sized, and fine solids, is preferably delivered to an intermediate blender (e.g., intermediate blender 660 of FIG.","6) for blending.","The present teachings recognize that the ratio of coarse, medium-sized, and fine solids in anaerobically activated organic waste delivered to the intermediate blender may be adjusted so as to optimize formulations for a plant life enhancing product, e.g., fertilizer, biocide, pesticide, and/or agricultural feed.","In doing so, the present arrangement recognizes that coarse solids produced by a solids separator (e.g., solids separator 604 of FIG.","6) are relatively less broken down than medium-sized solids produced by a DAF tank (e.g., DAF tank 606 of FIG.","6).","Likewise, medium-sized solids are relatively less broken down than fine solids produced by an SRT (e.g., SRT #1 608 of FIG.","6).","It is noteworthy that as these solids arc progressively broken down, nitrogen, in the form of ammonia, is made progressively more bioavailable.","Accordingly, the release of nitrogen in plant life enhancing compositions, such as fertilizer, pesticide, and/or biocide is optimized by adjusting the ratio of coarse, medium-sized, and fine solids in anaerobically activated organic waste.","By way of example, a fast-acting fertilizer, i.e., where nitrogen in the form of ammonia is readily available for uptake, may be comprised of relatively more fine solids, which contain more bioavailable nitrogen than coarse and medium-sized solids.","Likewise, a slow-acting fertilizer may be comprised of relatively more coarse solids, which contain nitrogen that is less bioavailable and therefore released more slowly, over a longer period of time.","Next, a step 704 includes aerobically digesting the ammonia-enriched water to produce aerobically activated organic residue.","Preferably, aerobic digestion is carried out in a series of components (e.g., BCR #1 610, BCR #2 612, and aerobic sludge digester 614 of FIG.","6) that facilitate removal of aerobically activated organic residue.","Though not shown in FIG.","7, ammonia-enriched water is preferably further treated in a series of components, including an SRT (e.g., SRT #2 616 of FIG.","6), an HRAP (e.g., HRAP 618 of FIG.","6), and another SRT (e.g., SRT #3 620), which facilitate removal of other solid byproducts of wastewater treatment, including dead microorganisms, algae-enriched slurry, and algae, respectively.","Next, a step 706 includes blending the anaerobically activated organic residue with the aerobically activated organic residue to produce fertilizer.","Though not shown in FIG.","7, other byproducts of wastewater treatment (e.g., dead microorganisms, algae-enriched slurry, and algae) are preferably also blended with anaerobically activated organic residue to produce fertilizer.","In preferred embodiments of the present arrangement, however, the blended product is a precursor to a plant life enhancing composition that is delivered to a dryer and a pelletizer to ultimately produce the plant life enhancing composition.","In a similar manner to that described above with reference to step 702, the ratio of each solid waste component blended in step 706 (e.g., anaerobically activated organic residue, dead microorganisms, algae-enriched slurry, and algae) may be delivered to the blender in ratios that produce optimized formulations of fertilizer.","In one embodiment of the present teachings, a plant life enhancing composition includes an effective amount of a bioavailable component that is available for immediate absorption by a plant and an effective amount of a precursor component, which has a more complex molecular structure than the bioavailable component.","Over a period of time the precursor component transforms into the bioavailable component.","In this embodiment, an effective amount of a catalyst is also provided.","The catalyst facilitates transformation of the precursor component (i.e., more complex molecules) to the bioavailable component (i.e., less complex molecules).","The period of time to transform the precursor component to a bioavailable component may vary depending on various factors, such as the temperature at which the plant enhancing composition is placed, amount of activating agent, such as water, and the complexity of the precursor component.","In one preferred embodiment of the present teachings, duration is a period of time that ranges from about one day to about six months.","An effective amount of the catalyst may be a value that ranges from about.","0.01% (by weight of the fertilizer) to about 2% (by weight of the fertilizer).","The catalyst may include an enzyme.","In the presence of the enzyme, the precursor component is transformed to the bioavailable component at a rate that may be between about 3 times and about 4 times faster than a rate of transforming the precursor component to the bioavailable component in absence of the catalyst.","In one embodiment of the present teachings, the enzyme includes at least one member chosen from a group comprising β-glucosidase, fluorescein diacetate hydrolysis, amidase, urease, phosphatase, sulfatase , endoglumayase, cellobiohydrolase, β-glucosidase cellobiohydrolase, endoxylanase, endomannanase, β-glycosidases, esterases, endochitinase, N-acetlyglucosaminidase, α-glucosidase, Mn-peroxidase, lignin peroxidase, laccase, phenoloxidase, proteases, aminopeptidases, urease, phosphomonoesterase, phospohodiesterase and arylsulfatase.","In the plant life enhancing composition, the bioavailable component includes an effective amount of micronutrient and/or an effective amount of macronutrient to enhance plant growth.","The effective amount of each of the micronutrient and the macronutrient is a value that may range from about 0.1% (by weight of the bioavailable component) to about 6% (by weight of the bioavailable component).","The micronutrient preferably includes at least one member selected from a group comprising boron, cobalt, chromium, copper, fluorine, iodine, molybdenum, selenium, zinc, chlorine, iron, manganese, zinc and nickel.","The macronutrient preferably includes at least one member selected from a group comprising nitrogen, potassium, calcium, magnesium, phosphorous, carbon and sulfur.","The precursor component preferably includes an effective amount of non-bioavailable forms of a member chosen from a group comprising boron, cobalt, chromium, copper, fluorine, iodine, molybdenum, selenium, zinc, chlorine, iron, manganese, zinc, nickel, nitrogen, potassium, calcium, magnesium, phosphorous, carbon and sulfur.","The effective amount of the precursor component may be a value that ranges from about 0.01% (by weight of the plant life enhancing composition) to about 10% (by weight of the plant life enhancing composition).","In other aspects, the plant life enhancing composition of the present teachings include an effective amount of a dormant component, which, in turn, may include any one of aerobically activated organic residue 627, dead bacteria 654, algae-enriched slurry 656 and algae 658).","In this aspect, an effective amount of a decomposed dormant component may also be present.","The decomposed dormant component includes an output of anaerobic digestion.","By way of example, decomposed dormant component includes anaerobically activated fine solids which may comprise any one of activated coarse solids 650, anaerobically activated medium-sized solids 624, and anaerobically activated fine solids 652.The resulting plant life enhancing composition, as discussed above, in some instances may not have a sufficient amount of a desired material.","To this end, the plant life enhancing composition may be admixed with an effective amount of an amendment to provide a predetermined amount of one more desired materials that are inorganic or organic in nature.","Examples of one or more of the desired materials may include sulfur and/or nitrogen.","In another embodiment, the present teachings provide a plant life enhancing composition that includes effective amounts of each of a dormant component, a decomposed dormant component and a catalyst.","The dormant component includes an output of aerobic digestion (e.g., aerobically activated organic residue) and the decomposed dormant component includes an output of anaerobic digestion (e.g., anaerobically activated organic residue), as discussed above.","The catalyst facilitates transformation of the dormant component to the decomposed dormant component.","Further, the catalyst may also transform the decomposed dormant component to a bioavailable component in the plant life enhancing composition of the present teachings.","Effective amount of each of the dormant and the decomposed dormant component may be a value that ranges from about 0.01% (by weight of the plant life enhancing component) to about 10% (by weight of the plant life enhancing component).","The effective amount of the catalyst is a value that may range from about 0.01% (by weight of the plant life enhancing component) to about 2% (by weight of the plant life enhancing component) and in presence of the catalyst.","Further, the dormant component is transformed to the decomposed dormant component at a rate that may be between about 3 times and about 4 times faster than a rate of transforming the dormant component to the decomposed dormant component in absence of the catalyst.","In one aspect, the present teachings propose that enzymes be used lo serve as catalysts, as they promote plant growth and effectively activate bacteria, which facilitates transforming the dormant component to the decomposed dormant component discussed above.","Although illustrative embodiments of the present teachings have been shown and described, other modifications, changes, and substitutions are intended.","Accordingly, it is appropriate that the appended claims be construed broadly and in a manner consistent with the scope of the disclosure, as set forth in the following claims."]],"string":"[\n [\n \"Novel Systems, Methods And Compositions Involving Plant Life Enhancing Products\",\n \"A method for producing a plant life enhancing product is described.\",\n \"The method includes: (i) anaerobically digesting agricultural residue to produce an anaerobically activated organic residue and an ammonia-enriched water; (ii) aerobically digesting the ammonia-enriched water to produce an aerobically activated organic residue; and (iii) blending the anaerobically activated organic residue with the aerobically activated organic residue to produce the plant life enhancing product.\"\n ],\n [\n \"1.A method for producing a plant life enhancing product, said method comprising; anaerobically digesting agricultural residue to produce an anaerobically activated organic residue and an ammonia-enriched water; aerobically digesting said ammonia-enriched water to produce an aerobically activated organic residue; and blending said anaerobically activated organic residue with said aerobically activated organic residue to produce said plant life enhancing product.\",\n \"2.The method of claim 1, wherein said anaerobically activated organic residue is blended following said anaerobically digesting agricultural residue.\",\n \"3.The method of claim 1, further comprising drying said plant life enhancing product to form a dried plant life enhancing product.\",\n \"4.The method of claim 3, further comprising pelletizing said dried plant life enhancing product.\",\n \"5.The method of claim 1, wherein said plant life enhancing product is used as at least one member selected from a group comprising biocide, pesticide, and agricultural feed product.\",\n \"6.The method of claim 1, further comprising removing solids from anaerobically activated organic residue.\",\n \"7.The method of claim 6, wherein said removing solids includes removing at least one member selected from a group comprising coarse solids, medium-sized solids, and fine solids.\"\n ],\n [\n \" BACKGROUND Large volumes of water are used in the operation of dairies and farms, where crops and animals are raised.\",\n \"The resulting wastewater is mainly organic in nature and nutrient rich.\",\n \"Moreover, a significant amount of organics and/or nutrients are in the form of complex molecules that are not readily absorbed by plants and animals.\",\n \"To keep up with a diminishing water supply in some regions and lower water and energy costs, attempted wastewater treatment solutions are passive in nature and offer no effective solution to recover the nutrients.\",\n \"The attempted solutions also fail to provide nutrients in a form that may be used by the plants and animals.\"\n ],\n [\n \" SUMMARY In view of the foregoing, the present teachings offer novel systems and methods for wastewater treatment and byproducts that provide plant and animal life enhancing products.\",\n \"In one aspect, the present teachings provide a system for producing plant life enhancing product.\",\n \"The system includes: (i) an anaerobic tank for anaerobically digesting agricultural residue to produce an anaerobically activated organic residue and an ammonia-enriched water; (ii) a solids removal sub-assembly for separating the ammonia-enriched water from the anaerobically activated organic residue to produce a substantially ammonia-free anaerobically activated organic residue; (iii) an aerobic tank for aerobically digesting the ammonia-enriched water to produce an aerobically activated organic residue; and (iv) a blending unit for blending the anaerobically activated organic residue with aerobically activated organic residue to produce the plant life enhancing product.\",\n \"In another aspect, the present teachings provide a method for producing a plant life enhancing product.\",\n \"The method includes: (i) anaerobically digesting agricultural residue to produce an anaerobically activated organic residue and an ammonia-enriched water; (ii) aerobically digesting the ammonia-enriched water to produce an aerobically activated organic residue; and (iii) blending the anaerobically activated organic residue with the aerobically activated organic residue to produce the plant life enhancing product.\",\n \"In yet another aspect, the present teachings provide a plant life enhancing composition.\",\n \"The plant life enhancing component includes: (i) an effective amount of a bioavailable component that is available for immediate absorption by a plant; (ii) an effective amount of a precursor component, which has a more complex molecular structure than the bioavailable component and over a duration transforms into the bioavailable component; and (iii) an effective amount of a catalyst that facilitates transformation of the precursor component to the bioavailable component.\",\n \"In yet another aspect, the present teachings provide another plant life enhancing composition comprising: (i) an effective amount of a dormant component, which includes an output of aerobic digestion; (ii) an effective amount of a decomposed dormant component, which includes an output of anaerobic digestion; and (iii) an effective amount of a catalyst that facilitates transformation of the dormant component to the decomposed dormant component.\",\n \"Conventional wastewater treatments typically release noxious gases into the environment, contributing to the greenhouse effect.\",\n \"The present teachings provide novel systems and methods for capturing those gases, converting those gases into useful energy, and doing so preferably in a substantially closed system.\",\n \"It is an objective, among many, of the present teachings to convert otherwise harmful byproducts to useful energy, preferably using some of the treated water resulting from wastewater treatment.\",\n \"The approach adopted by the present teachings recognizes, among other things, that the concept of biochemical oxygen demand (“BOD”) drives various steps of wastewater treatment.\",\n \"BOD is a well-known parameter, which indicates the amount of oxygen needed to biologically stabilize the organic matter present.\",\n \"According to preferred embodiments of the present teachings, efforts to effectively control BOD levels in various stages of wastewater treatment rely upon more than gravity and time.\",\n \"This allows the present teachings to offer active treatment of wastewater, as opposed to prior art's passive treatment, which relies only upon gravity and time.\",\n \"Organic matter commonly present in wastewater uses oxygen for various reasons and as a result, depletes soluble oxygen.\",\n \"A requisite high level of dissolved oxygen, however, is desirable during certain stages of treatment to grow microorganisms to consume organic matter present in wastewater treatment.\",\n \"Conventional methods only in a single discrete step grow microorganisms by introducing oxygen to replenish the depleted levels of oxygen in wastewater.\",\n \"This step provides oxygen to initially promote growth of naturally occurring microorganisms to large numbers so that they consume almost all of the organic matter and oxygen in wastewater.\",\n \"Conventional methods introduce oxygen by implementing passive means, i.e., requiring a large space-consuming tank to expose a greater surface area to the atmosphere for long periods of time.\",\n \"The present teachings recognize the need to maximize use of high-pressure air diffusion in multiple steps to actively increase the amount of dissolved oxygen in wastewater as well as creating an active environment for naturally occurring and custom introduced bacteria to grow by increasing the surface-area-to-volume ratio in specific reactors.\",\n \"In preferred embodiments of the present teachings, this process of actively introducing oxygen and increasing surface-area-to-volume ratio begins early, during a solids-removal stage, and well before microorganisms growth is encouraged in conventional methods.\",\n \"When sufficient amount of microorganisms die in an oxygen- and nutrient-poor environment, dead organisms undergo decay, raising levels of ammonia, nitrate, and nitrite through a process known as “nitrification.” Conventional treatment discharges the wastewater with a high concentration of nitrogen and phosphorous to the environment.\",\n \"Reverse osmosis and ion exchange are known to remove nitrogen and phosphorous, but are not deemed commercially viable and are therefore not integrated into conventional wastewater treatment methods.\",\n \"Discharge of nutrient-rich effluent is known to be injurious to life.\",\n \"Nitrates are carcinogenic and direct discharge of wastewater with nitrates may contaminate drinking water aquifers.\",\n \"The present teachings recognize this and prevents such contamination by effectively removing nitrogen and phosphorous from wastewater before discharge.\",\n \"Preferred embodiments of the present teachings effectively treat wastewater by driving down BOD, maintaining the level of dissolved oxygen, lowering the solid content, and controlling the nutrient level in wastewater at various stages.\",\n \"By way of example, in one stage, the present teachings drive down BOD and solid content in wastewater by actively focusing on the removal of BOD-contributing solids.\",\n \"As another example, during the process of removing solids, the present teachings also focus on improving the growth regime for naturally occurring and genetically engineered bacteria.\",\n \"Preferred embodiments of the present teachings use high-pressure air diffusion to substantially maintain or increase the level of dissolved oxygen in wastewater.\",\n \"As a result, according to preferred embodiments of the present teachings, microorganism growth is encouraged well before they are employed to remove organic matter.\",\n \"As yet another example, directly after removal of organic matter by microorganism consumption, preferred embodiments treat wastewater by creating anaerobic conditions to achieve complete microorganism die off and lower solid content or reduce BOD in wastewater.\",\n \"Next, the wastewater is treated to remove solids and further reduce BOD in an aerobic environment, which replenishes the dissolved oxygen levels.\",\n \"As yet another example, preferred embodiments of the present teachings, while actively removing BOD-contributing solids, dead microorganisms, nutrients, algae, and other solids, maintain the level of dissolved oxygen in wastewater to prevent an increase of BOD and solid content by reversible reaction.\",\n \"It is important to note that prior art fails to recognize drawbacks of reversible reactions, which increase BOD, let alone offer provisions to prevent increase of BOD.\",\n \"As yet another example, preferred embodiments of the present teachings drive down the nutrients in wastewater by actively focusing on the removal of all forms of nitrogen and phosphates by effectively cultivating specific biological processes that utilize nutrients available for their own growth.\",\n \"The teachings further reduce the nutrient load by actively removing any biological matter remaining in the effluent.\",\n \"As yet another example, the present teachings offer provisions to capture methane and other components of biogas to convert methane into electricity and to convert other components of biogas and byproducts of the electricity conversion process to chemical species, which promote growth or production of useful products.\",\n \"In preferred embodiments of the present teachings, a portion of treated water resulting from wastewater treatment is used in conjunction with biogas and gases produced during anaerobic and aerobic digestion, respectively, in a useful manner as opposed to releasing such gases to the atmosphere, as conventional processes do.\",\n \"In yet another aspect, the present teachings provide a method for removing methane from biogas.\",\n \"The method includes: (i) receiving biogas including methane and other components into a first tank; (ii) receiving water into the first tank; (iii) contacting the biogas with the water inside the first tank; (iv) dispensing methane gas from an outlet of the first tank; and (v) producing from the tank an effluent stream that includes other components of the biogas.\",\n \"The step of contacting may include passing bubbles of biogas through the water.\",\n \"Water may be obtained from any source of purified water.\",\n \"Preferably, however, water is obtained from a wastewater treatment facility.\",\n \"In one embodiment of the present teachings, the inventive methods may further include a step of carrying out digestion of water enriched with organic matter in a second tank to produce the biogas.\",\n \"The second tank may be different from the first tank.\",\n \"The organic matter in the water may be between about 0.5% by volume and about 25% by volume.\",\n \"In preferred embodiments of the present teachings, inventive methods include a step of sending the effluent stream from the tank to a diffused air flotation (“DAF”) tank that is designed to effect removal of solids.\",\n \"Inventive methods may further include a step of sending the methane gas to an electrical generator that is designed to burn methane gas and produce electrical energy.\",\n \"Preferably, the electrical generator produces exhaust gases which include at least one of CO 2 gas, SO x gas, and NO x gas, and are treated in a third tank by contacting the exhaust gases with water to remove at least one of CO 2 gas, SO x gas, and NO x gas from the third tank and produce water having dissolved therein at least one of CO 2 gas, SO x gas, and NO x gas.\",\n \"More preferably, the water having dissolved therein at least one of CO 2 gas, SO x gas, and NO x gas is delivered to an algal pond.\",\n \"The algal pond may be a high rate algal pond (“HRAP”).\",\n \"In yet another aspect, the present teachings provide a method for removing byproduct gases after aerobic digestion.\",\n \"The method includes: (i) receiving into a first tank a gaseous mixture including at least one of ammonia gas and sulfur gas; (ii) receiving water into the first tank; (iii) contacting the gaseous mixture including at least one of the ammonia gas and the sulfur gas with the water inside the first tank to produce an effluent stream of water having dissolved therein the at least one of aqueous ammonia and sulfur and produce a residual gaseous mixture including at least one of ammonia gas and sulfur gas; (iv) dispensing residual gas including at least one of residual ammonia gas and residual sulfur gas; and (v) discharging the effluent stream including water which has dissolved therein the at least one of aqueous ammonia and sulfur gas.\",\n \"Residual gaseous mixture refers to the gas or gases that do not dissolve in water.\",\n \"The step of dispensing may include recirculating the residual gaseous mixture from outlet of the first tank to an inlet of the first tank.\",\n \"The step of contacting may include passing bubbles of the gaseous mixture through the water.\",\n \"In yet another aspect, the present teachings provide a system for removing byproducts of anaerobic digestion.\",\n \"The system includes: (i) a first tank including: (a) a first inlet that is connected to receive byproduct gases of anaerobic digestion including at least one gas and methane, (b) a first outlet that provides methane gas as exhaust, (c) a second inlet that is connected to receive a stream of water, and (d) a second outlet that discharges an effluent water stream having dissolved therein the above-mentioned at least one gas into a tank designed for removing solids; and (ii) an electrical generator that is connected to the first outlet of the first tank; and wherein the first tank is designed to contact the stream of water with the byproduct gases of anaerobic digestion and produce the effluent stream of water.\",\n \"In preferred embodiments, the electrical generator produces electricity and a gas including at least one of CO 2 gas, SO x gas, and NO x gas.\",\n \"In yet another aspect, the present teachings provide a system for wastewater treatment.\",\n \"The system includes: (i) a solids-removal subassembly designed to remove solids from wastewater and produce solids-depleted water; (ii) an assembly designed for processing organic material in the solids-depleted wastewater to produce treated water and the assembly connected to the solids-removal subassembly; (iii) a tank that has a first inlet, a first outlet, and a second outlet; and (iv) wherein the first inlet of the tank is designed to receive treated water, the first outlet is designed to discharge a first portion of treated water, the second outlet is designed to discharge a second portion of treated water, and the first portion of treated water is used for processing byproduct gases resulting from wastewater treatment.\",\n \"Preferably, the tank may be a holding tank that is located downstream from a nutrient-removal tank, which is designed to remove nutrients from wastewater.\",\n \"In alternative embodiments of the present teachings, the tank is a nutrient-removal tank designed to remove nutrients from wastewater In yet another aspect, the present teachings provide a method of wastewater treatment.\",\n \"The method includes the steps of: (i) removing solids from wastewater to produce solids-depleted water; (ii) processing organic material in the solids-depleted wastewater to produce treated water; (iii) discharging a first portion of treated water and a second portion of treated water; and (iv) using the first portion of treated water to process byproduct gases resulting from wastewater treatment.\",\n \"In preferred embodiments, the present teachings provide the further step of removing nutrients from wastewater.\",\n \"The above-mentioned step of using may be carried out after removing nutrients.\",\n \"The construction and method of operation of the teachings, however, together with additional objects and advantages thereof will be best understood from the following descriptions of specific embodiments when read in connection with the accompanying figures.\"\n ],\n [\n \"RELATED APPLICATION This application claims priority to U.S.\",\n \"Provisional Application No.\",\n \"61/727,097, filed on Nov. 15, 2012, entitled “Novel Systems And Methods For Treatment Of Gaseous And Solid Byproducts Of Wastewater Treatment”, which is related to U.S. patent application Ser.\",\n \"No.\",\n \"13/750,989, filed Jan. 25, 2013, entitled “Novel Systems And Methods For Converting Gaseous Byproducts Of Wastewater Treatment Into Energy”, which claims priority to and is a divisional of U.S. patent application Ser.\",\n \"No.\",\n \"12/577,129 filed on Oct. 9, 2009, which is now U.S. Pat.\",\n \"No.\",\n \"8,382,983, issued Feb. 26, 2013, all of which are incorporated herein for all purposes.\",\n \"FIELD The present teachings relate generally to wastewater treatment and byproducts thereof.\",\n \"More particularly, the present teachings relate to novel systems, methods and compositions involving plant life enhancing products produced from wastewater treatment and/or byproducts thereof.\",\n \"BACKGROUND Large volumes of water are used in the operation of dairies and farms, where crops and animals are raised.\",\n \"The resulting wastewater is mainly organic in nature and nutrient rich.\",\n \"Moreover, a significant amount of organics and/or nutrients are in the form of complex molecules that are not readily absorbed by plants and animals.\",\n \"To keep up with a diminishing water supply in some regions and lower water and energy costs, attempted wastewater treatment solutions are passive in nature and offer no effective solution to recover the nutrients.\",\n \"The attempted solutions also fail to provide nutrients in a form that may be used by the plants and animals.\",\n \"SUMMARY In view of the foregoing, the present teachings offer novel systems and methods for wastewater treatment and byproducts that provide plant and animal life enhancing products.\",\n \"In one aspect, the present teachings provide a system for producing plant life enhancing product.\",\n \"The system includes: (i) an anaerobic tank for anaerobically digesting agricultural residue to produce an anaerobically activated organic residue and an ammonia-enriched water; (ii) a solids removal sub-assembly for separating the ammonia-enriched water from the anaerobically activated organic residue to produce a substantially ammonia-free anaerobically activated organic residue; (iii) an aerobic tank for aerobically digesting the ammonia-enriched water to produce an aerobically activated organic residue; and (iv) a blending unit for blending the anaerobically activated organic residue with aerobically activated organic residue to produce the plant life enhancing product.\",\n \"In another aspect, the present teachings provide a method for producing a plant life enhancing product.\",\n \"The method includes: (i) anaerobically digesting agricultural residue to produce an anaerobically activated organic residue and an ammonia-enriched water; (ii) aerobically digesting the ammonia-enriched water to produce an aerobically activated organic residue; and (iii) blending the anaerobically activated organic residue with the aerobically activated organic residue to produce the plant life enhancing product.\",\n \"In yet another aspect, the present teachings provide a plant life enhancing composition.\",\n \"The plant life enhancing component includes: (i) an effective amount of a bioavailable component that is available for immediate absorption by a plant; (ii) an effective amount of a precursor component, which has a more complex molecular structure than the bioavailable component and over a duration transforms into the bioavailable component; and (iii) an effective amount of a catalyst that facilitates transformation of the precursor component to the bioavailable component.\",\n \"In yet another aspect, the present teachings provide another plant life enhancing composition comprising: (i) an effective amount of a dormant component, which includes an output of aerobic digestion; (ii) an effective amount of a decomposed dormant component, which includes an output of anaerobic digestion; and (iii) an effective amount of a catalyst that facilitates transformation of the dormant component to the decomposed dormant component.\",\n \"Conventional wastewater treatments typically release noxious gases into the environment, contributing to the greenhouse effect.\",\n \"The present teachings provide novel systems and methods for capturing those gases, converting those gases into useful energy, and doing so preferably in a substantially closed system.\",\n \"It is an objective, among many, of the present teachings to convert otherwise harmful byproducts to useful energy, preferably using some of the treated water resulting from wastewater treatment.\",\n \"The approach adopted by the present teachings recognizes, among other things, that the concept of biochemical oxygen demand (“BOD”) drives various steps of wastewater treatment.\",\n \"BOD is a well-known parameter, which indicates the amount of oxygen needed to biologically stabilize the organic matter present.\",\n \"According to preferred embodiments of the present teachings, efforts to effectively control BOD levels in various stages of wastewater treatment rely upon more than gravity and time.\",\n \"This allows the present teachings to offer active treatment of wastewater, as opposed to prior art's passive treatment, which relies only upon gravity and time.\",\n \"Organic matter commonly present in wastewater uses oxygen for various reasons and as a result, depletes soluble oxygen.\",\n \"A requisite high level of dissolved oxygen, however, is desirable during certain stages of treatment to grow microorganisms to consume organic matter present in wastewater treatment.\",\n \"Conventional methods only in a single discrete step grow microorganisms by introducing oxygen to replenish the depleted levels of oxygen in wastewater.\",\n \"This step provides oxygen to initially promote growth of naturally occurring microorganisms to large numbers so that they consume almost all of the organic matter and oxygen in wastewater.\",\n \"Conventional methods introduce oxygen by implementing passive means, i.e., requiring a large space-consuming tank to expose a greater surface area to the atmosphere for long periods of time.\",\n \"The present teachings recognize the need to maximize use of high-pressure air diffusion in multiple steps to actively increase the amount of dissolved oxygen in wastewater as well as creating an active environment for naturally occurring and custom introduced bacteria to grow by increasing the surface-area-to-volume ratio in specific reactors.\",\n \"In preferred embodiments of the present teachings, this process of actively introducing oxygen and increasing surface-area-to-volume ratio begins early, during a solids-removal stage, and well before microorganisms growth is encouraged in conventional methods.\",\n \"When sufficient amount of microorganisms die in an oxygen- and nutrient-poor environment, dead organisms undergo decay, raising levels of ammonia, nitrate, and nitrite through a process known as “nitrification.” Conventional treatment discharges the wastewater with a high concentration of nitrogen and phosphorous to the environment.\",\n \"Reverse osmosis and ion exchange are known to remove nitrogen and phosphorous, but are not deemed commercially viable and are therefore not integrated into conventional wastewater treatment methods.\",\n \"Discharge of nutrient-rich effluent is known to be injurious to life.\",\n \"Nitrates are carcinogenic and direct discharge of wastewater with nitrates may contaminate drinking water aquifers.\",\n \"The present teachings recognize this and prevents such contamination by effectively removing nitrogen and phosphorous from wastewater before discharge.\",\n \"Preferred embodiments of the present teachings effectively treat wastewater by driving down BOD, maintaining the level of dissolved oxygen, lowering the solid content, and controlling the nutrient level in wastewater at various stages.\",\n \"By way of example, in one stage, the present teachings drive down BOD and solid content in wastewater by actively focusing on the removal of BOD-contributing solids.\",\n \"As another example, during the process of removing solids, the present teachings also focus on improving the growth regime for naturally occurring and genetically engineered bacteria.\",\n \"Preferred embodiments of the present teachings use high-pressure air diffusion to substantially maintain or increase the level of dissolved oxygen in wastewater.\",\n \"As a result, according to preferred embodiments of the present teachings, microorganism growth is encouraged well before they are employed to remove organic matter.\",\n \"As yet another example, directly after removal of organic matter by microorganism consumption, preferred embodiments treat wastewater by creating anaerobic conditions to achieve complete microorganism die off and lower solid content or reduce BOD in wastewater.\",\n \"Next, the wastewater is treated to remove solids and further reduce BOD in an aerobic environment, which replenishes the dissolved oxygen levels.\",\n \"As yet another example, preferred embodiments of the present teachings, while actively removing BOD-contributing solids, dead microorganisms, nutrients, algae, and other solids, maintain the level of dissolved oxygen in wastewater to prevent an increase of BOD and solid content by reversible reaction.\",\n \"It is important to note that prior art fails to recognize drawbacks of reversible reactions, which increase BOD, let alone offer provisions to prevent increase of BOD.\",\n \"As yet another example, preferred embodiments of the present teachings drive down the nutrients in wastewater by actively focusing on the removal of all forms of nitrogen and phosphates by effectively cultivating specific biological processes that utilize nutrients available for their own growth.\",\n \"The teachings further reduce the nutrient load by actively removing any biological matter remaining in the effluent.\",\n \"As yet another example, the present teachings offer provisions to capture methane and other components of biogas to convert methane into electricity and to convert other components of biogas and byproducts of the electricity conversion process to chemical species, which promote growth or production of useful products.\",\n \"In preferred embodiments of the present teachings, a portion of treated water resulting from wastewater treatment is used in conjunction with biogas and gases produced during anaerobic and aerobic digestion, respectively, in a useful manner as opposed to releasing such gases to the atmosphere, as conventional processes do.\",\n \"In yet another aspect, the present teachings provide a method for removing methane from biogas.\",\n \"The method includes: (i) receiving biogas including methane and other components into a first tank; (ii) receiving water into the first tank; (iii) contacting the biogas with the water inside the first tank; (iv) dispensing methane gas from an outlet of the first tank; and (v) producing from the tank an effluent stream that includes other components of the biogas.\",\n \"The step of contacting may include passing bubbles of biogas through the water.\",\n \"Water may be obtained from any source of purified water.\",\n \"Preferably, however, water is obtained from a wastewater treatment facility.\",\n \"In one embodiment of the present teachings, the inventive methods may further include a step of carrying out digestion of water enriched with organic matter in a second tank to produce the biogas.\",\n \"The second tank may be different from the first tank.\",\n \"The organic matter in the water may be between about 0.5% by volume and about 25% by volume.\",\n \"In preferred embodiments of the present teachings, inventive methods include a step of sending the effluent stream from the tank to a diffused air flotation (“DAF”) tank that is designed to effect removal of solids.\",\n \"Inventive methods may further include a step of sending the methane gas to an electrical generator that is designed to burn methane gas and produce electrical energy.\",\n \"Preferably, the electrical generator produces exhaust gases which include at least one of CO2 gas, SOx gas, and NOx gas, and are treated in a third tank by contacting the exhaust gases with water to remove at least one of CO2 gas, SOx gas, and NOx gas from the third tank and produce water having dissolved therein at least one of CO2 gas, SOx gas, and NOx gas.\",\n \"More preferably, the water having dissolved therein at least one of CO2 gas, SOx gas, and NOx gas is delivered to an algal pond.\",\n \"The algal pond may be a high rate algal pond (“HRAP”).\",\n \"In yet another aspect, the present teachings provide a method for removing byproduct gases after aerobic digestion.\",\n \"The method includes: (i) receiving into a first tank a gaseous mixture including at least one of ammonia gas and sulfur gas; (ii) receiving water into the first tank; (iii) contacting the gaseous mixture including at least one of the ammonia gas and the sulfur gas with the water inside the first tank to produce an effluent stream of water having dissolved therein the at least one of aqueous ammonia and sulfur and produce a residual gaseous mixture including at least one of ammonia gas and sulfur gas; (iv) dispensing residual gas including at least one of residual ammonia gas and residual sulfur gas; and (v) discharging the effluent stream including water which has dissolved therein the at least one of aqueous ammonia and sulfur gas.\",\n \"Residual gaseous mixture refers to the gas or gases that do not dissolve in water.\",\n \"The step of dispensing may include recirculating the residual gaseous mixture from outlet of the first tank to an inlet of the first tank.\",\n \"The step of contacting may include passing bubbles of the gaseous mixture through the water.\",\n \"In yet another aspect, the present teachings provide a system for removing byproducts of anaerobic digestion.\",\n \"The system includes: (i) a first tank including: (a) a first inlet that is connected to receive byproduct gases of anaerobic digestion including at least one gas and methane, (b) a first outlet that provides methane gas as exhaust, (c) a second inlet that is connected to receive a stream of water, and (d) a second outlet that discharges an effluent water stream having dissolved therein the above-mentioned at least one gas into a tank designed for removing solids; and (ii) an electrical generator that is connected to the first outlet of the first tank; and wherein the first tank is designed to contact the stream of water with the byproduct gases of anaerobic digestion and produce the effluent stream of water.\",\n \"In preferred embodiments, the electrical generator produces electricity and a gas including at least one of CO2 gas, SOx gas, and NOx gas.\",\n \"In yet another aspect, the present teachings provide a system for wastewater treatment.\",\n \"The system includes: (i) a solids-removal subassembly designed to remove solids from wastewater and produce solids-depleted water; (ii) an assembly designed for processing organic material in the solids-depleted wastewater to produce treated water and the assembly connected to the solids-removal subassembly; (iii) a tank that has a first inlet, a first outlet, and a second outlet; and (iv) wherein the first inlet of the tank is designed to receive treated water, the first outlet is designed to discharge a first portion of treated water, the second outlet is designed to discharge a second portion of treated water, and the first portion of treated water is used for processing byproduct gases resulting from wastewater treatment.\",\n \"Preferably, the tank may be a holding tank that is located downstream from a nutrient-removal tank, which is designed to remove nutrients from wastewater.\",\n \"In alternative embodiments of the present teachings, the tank is a nutrient-removal tank designed to remove nutrients from wastewater In yet another aspect, the present teachings provide a method of wastewater treatment.\",\n \"The method includes the steps of: (i) removing solids from wastewater to produce solids-depleted water; (ii) processing organic material in the solids-depleted wastewater to produce treated water; (iii) discharging a first portion of treated water and a second portion of treated water; and (iv) using the first portion of treated water to process byproduct gases resulting from wastewater treatment.\",\n \"In preferred embodiments, the present teachings provide the further step of removing nutrients from wastewater.\",\n \"The above-mentioned step of using may be carried out after removing nutrients.\",\n \"The construction and method of operation of the teachings, however, together with additional objects and advantages thereof will be best understood from the following descriptions of specific embodiments when read in connection with the accompanying figures.\",\n \"BRIEF DESCRIPTION OF THE DRAWINGS FIG.\",\n \"1A shows an exemplar system for wastewater treatment, according to one present arrangement.\",\n \"FIG.\",\n \"1B shows an exemplar system, according to one embodiment of the present teachings, for separating methane gas from biogas that is produced after anaerobic digestion.\",\n \"FIG.\",\n \"1C shows an exemplar system, according to one present arrangement, for treating gas produced by aerobic and anaerobic digestion.\",\n \"FIG.\",\n \"2 shows details of a BCR design, according to one present arrangement, used in the system of FIG.\",\n \"1A.\",\n \"FIG.\",\n \"3 shows an exemplar algal pond used in the system of FIG.\",\n \"1A.\",\n \"FIG.\",\n \"4 shows a perspective view of the algal pond of FIG.\",\n \"3.FIG.\",\n \"5 shows an exemplar system, according to one present arrangement, for converting methane gas into electricity.\",\n \"FIG.\",\n \"6 shows an exemplar system for converting solid byproducts of wastewater treatment into plant life enhancing product, e.g., fertilizer, pesticide, biocide, and/or agricultural feed, according to one present arrangement.\",\n \"FIG.\",\n \"7 shows an exemplar flow diagram, according to one present arrangement, for converting solid byproducts of wastewater treatment into plant life enhancing products (e.g., fertilizer, pesticide, biocide, and/or agricultural feed).\",\n \"DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS In the following description numerous specific details are set forth in order to provide a thorough understanding of the present teachings.\",\n \"It will be apparent, however, to one skilled in the art that the present teachings may be practiced without limitation to some or all of these specific details.\",\n \"In other instances, well known process steps have not been described in detail in order to not unnecessarily obscure the teachings.\",\n \"FIG.\",\n \"1A shows a system design 100, according to one embodiment of the present teachings, for active treatment of wastewater.\",\n \"System 100 includes an anaerobic tank 102, inside which anaerobic digestion of wastewater takes place.\",\n \"In other words, inside anaerobic tank 102, organic content in wastewater is broken down into simpler molecules, which may be further treated by other methods.\",\n \"A byproduct of anaerobic digestion, biogas 128, is collected at the top surface of anaerobic tank 102 (not shown to simplify illustration) and delivered to a system for treatment resulting in product that may be converted into clean energy (described below with reference to FIGS.\",\n \"1B and 5).\",\n \"System design 100 provides wastewater that has undergone anaerobic digestion to a series of active devices for removal of solid waste.\",\n \"These active devices include a solids separator 104, a DAF tank 106, and a first SRT 108, each of which facilitates removal of solid contaminants of different sizes and type.\",\n \"The relatively solid-free wastewater is then transported to a series of BCRs 110 and 112 to remove organic matter.\",\n \"For removal of solid sludge, if necessary, an aerobic sludge digester tank 114 is provided.\",\n \"Wastewater containing dead microorganisms from either BCR 112 or from aerobic sludge digester 114, if one is employed, is sent to a second SRT 116 for removal of solids, which include for the most part dead microorganisms.\",\n \"For further removal of dead organisms, the wastewater is treated in DAF tank 106 and from there sent to HRAP 118.HRAP 118 is provided to remove nutrients, such as nitrates, nitrites, and phosphorous from the wastewater.\",\n \"Next, wastewater is passed again through DAF tank 106 and through a third SRT 120 to specifically remove algae introduced into wastewater from HRAP 118.DAF tank 106 also serves to increase level of dissolved oxygen in wastewater.\",\n \"The nutrient-and-algae-depleted wastewater is optionally provided to a maturation pond 122 before discharging to the environment.\",\n \"In maturation pond 122, residual algae not removed in either DAF tank 106 or SRT 120 is removed and treated wastewater is exposed to elements of the natural environment.\",\n \"In preferred embodiments of the present teachings, a portion of the effluent stream flowing through line 125 from maturation pond 122 facilitates conversion of various byproducts of wastewater treatment (described below with reference to FIGS.\",\n \"1B and 1C) to useful energy (described below with reference to FIG.\",\n \"5) or useful downstream products (described below with reference to FIGS.\",\n \"1B, 1C, and 5).\",\n \"System 100 also includes various lines or connections between the different tanks to transport residual solids that are removed from the wastewater.\",\n \"According to FIG.\",\n \"1A, one such line 124 is provided between DAF tank 106 and anaerobic tank 102 to transport those solids which are not removed after treatment in DAF tank 106 back to a subsystem for drying and pelletizing.\",\n \"Another line 127 is also provided to transport solids, which typically include dead microorganisms, from aerobic sludge digester 114 to a subsystem designed for drying and pelletizing.\",\n \"The resulting pellets are used for fertilizer, pesticide, and/or biocide (described below with reference to FIGS.\",\n \"6 and 7).\",\n \"According to the embodiment shown in FIG.\",\n \"1A, residual solids are not only transported from aerobic sludge digester 114, but are also transported to digester 114.Specifically, a line 128 is provided to transport residual solids from DAF tank 106 back to aerobic sludge digester 114.In addition to conveying wastewater at different stages of treatment and conveying residual solids, various lines or connections between the different tanks of system 100 deliver biogas and gas to produce energy and other useful downstream products.\",\n \"By way of example, a gaseous mixture 128, which includes methane and other gases captured as byproducts of anaerobic digestion inside anaerobic tank 102, is transported to a tank 126 shown in FIG.\",\n \"1B.\",\n \"In preferred embodiments of the present teachings, tank 126 is a scrubber designed to contact gaseous mixture 128 with liquid stream 125.As another example, a portion of effluent stream 125 from maturation pond 122 is used to contact gaseous mixture 142 of FIG.\",\n \"1C.\",\n \"FIG.\",\n \"1C, described in greater detail below, shows processing of the gas or gaseous mixture resulting from aerobic digestion.\",\n \"From tank 126 of FIG.\",\n \"1B, a line 130 is provided to DAF tank 106 (as shown in FIG.\",\n \"1A) to deliver an effluent water stream having dissolved therein certain biogas components, such as ammonia, carbon dioxide, hydrogen, and sulfur, but not including methane, for further treatment.\",\n \"A detailed description of FIG.\",\n \"1B explains how the effluent entering DAF tank 106 shown in FIG.\",\n \"1A is produced.\",\n \"In system 100, gas (which includes ammonia gas and sulfur gas) emanating from processing of organic matter inside BCR 110 (shown in FIG.\",\n \"1A) is delivered via line 142 to a tank 140.Tank 140 is preferably a scrubber that is configured to contact a portion of treated water 125 (shown in FIGS.\",\n \"1A and 1B), for example, with the gas generated inside BCR 110.In other embodiments of the present teachings, instead of using a portion of treated water stream 125, any water stream that is relatively pure may be used.\",\n \"Solids separator 104 comes equipped with a screen designed to remove solids that do not settle out in anaerobic tank 102 or that are pulled into system 100 by the inlet pumps (not shown to simplify illustration of FIG.\",\n \"1A).\",\n \"Solids in wastewater that pass through the screen are pressed between at least two belts, each of which is supported by turning rollers positioned throughout the press.\",\n \"The belts are permeable and allow wastewater to pass through, holding back heavy solids.\",\n \"Moving action of the belt and the splashing of wastewater, as it permeates the belt, also serve to introduce oxygen into wastewater.\",\n \"The resulting increased level of dissolved oxygen encourages growth of microorganisms, which remove organic matter in a subsequent step.\",\n \"Depending on the screen size, solids separator 104 removes between about 75% and about 98% of solids removed from wastewater, which at this stage of treatment typically has a solid content that is between about 15% and about 30%.\",\n \"Eliminating these solids represents a significant amount of BOD removal.\",\n \"Solids removed by the press may be composted or otherwise removed from the premises for disposal.\",\n \"Solids separator 104 may be made from any rigid material, but is preferably made from stainless steel.\",\n \"Similarly, a range of suitable dimensions work well.\",\n \"In one preferred embodiment of the present teachings, system 100 uses a solids separator commercially available from Press Technologies of Wheat Ridge, Colorado.\",\n \"DAF tank 106 captures small particulate matter that is not removed by solids separator 104.To effect solid separation from wastewater, DAF tank 106, in accordance with one embodiment of the present teachings, uses a pored diffuser and a high-pressure pump that is preferably fitted with a venturi tube and is designed to introduce air bubbles inside wastewater.\",\n \"The pump draws in air, forcing air bubbles through the pored diffuser to form micro-air bubbles.\",\n \"The pored diffuser may be made from stone.\",\n \"Air is forced through the pored diffuser to produce a diffused air flow, preferably of about 40 cubic feet per minute.\",\n \"Air bubbles in their upward motion accumulate on the particulate matter and carry with them particulate matter to the top, where they are removed via skimmers.\",\n \"Air bubbles inside DAF tank provide a large surface area to effectively dissolve oxygen and thereby raise the level of soluble oxygen in wastewater.\",\n \"As a result, air bubbles not only facilitate removal of solids, but also increase the level of dissolved oxygen in wastewater to promote microorganism growth for subsequent removal of organic matter.\",\n \"Thus, the present teachings promote conditions for effective removal of organic matter in early stages and well before such removal is the primary focus during subsequent treatment.\",\n \"In preferred embodiments of the present teachings, DAF tank is commercially available from Martint Environmental of Lexington, S.C. By way of example, a DAF tank used in the present teachings is about 7 feet long, 3.5 feet wide, and 5 feet high.\",\n \"Hydraulic residence time in a DAF tank may be between about 1 and about 3 hours.\",\n \"Hydraulic residence time refers to the amount of time it takes for a single molecule of water to pass through the unit from the time it enters a tank, for example, to the time it leaves.\",\n \"DAF tank removes between about 85% and about 95% of the solids removed from wastewater, which at this point has a solid content that is between about 3% and about 6%.\",\n \"Unlike conventional solid sedimentation in the prior art, the present teachings do not require solids to fully settle to the bottom of the SRT to be trapped there.\",\n \"SRT 108 effects separation of residual solids by actively increasing the hydraulic flow path and providing physical impediments to particles for permanently trapping them.\",\n \"Hydraulic flow path refers to a path that is traversed by wastewater.\",\n \"An increase in the hydraulic flow path allows for separating a greater amount of solids from wastewater.\",\n \"SRT 108 is preferably large enough such that it takes wastewater being pumped in at 40 gallons per minute 100 minutes to fill it.\",\n \"U.S. Pat.\",\n \"No.\",\n \"6,899,808, which is incorporated herein by reference for all purposes, describes preferred embodiments of the SRT used in the present teachings.\",\n \"Surface area inside SRT 108 is preferably between about 160 square feet and about 320 square feet.\",\n \"SRT removes between about 85% and about 90% of solids having particle sizes greater than 20 micrometers from wastewater, which at this point has a solid content of about 1%.\",\n \"During the solid removal process, SRT 108 effects diffused air flow to raise level of dissolved oxygen in wastewater and to clean the screens provided for solid removal.\",\n \"By reducing ROD level and solid content and raising level of dissolved oxygen in wastewater, the present teachings promote conditions for removal of organic matter in early stages and well before such removal is the primary focus during subsequent treatment.\",\n \"FIG.\",\n \"2 shows a cross-sectional view of a BCR 200 (e.g., BCRS 110 and 112), in accordance with one embodiment of the present teachings.\",\n \"BCR 200 includes a tank 202, which contains biological chips 214 and has an inlet 208 for providing wastewater (not shown to simplify illustration) for treatment.\",\n \"Tank 202 is equipped with a blower 204 which introduces air inside wastewater.\",\n \"Waste solids in wastewater form a layer 212 and are removed by a pump 210.Biological chips 214 and blower 204 serve to provide wastewater with very high dissolved oxygen concentration and a high surface-area-to-volume ratio to aid the metabolic growth rates of microorganisms (not shown in FIG.\",\n \"2 to simplify illustration).\",\n \"BCR is an aerobic treatment system that utilizes microorganisms attached to biologic chips to form a biological film or slime layer (typically ranging from 0.1 mm to 0.2 mm thick).\",\n \"Microorganisms in the outer part of slime layer degrade the organic material in wastewater.\",\n \"However, as the slime layer thickens, oxygen is unable to penetrate the biological chips and anaerobic organisms develop.\",\n \"Eventually the microorganisms near the surface lose their ability to cling to the biological chips, and a portion of the slime layer falls off.\",\n \"In accordance with one embodiment of the present teachings, microorganisms inside a BCR include aerobic, anaerobic and facultative bacteria, fungi, and protozoa.\",\n \"BCR 110 is preferably designed to contain many different types of microorganisms, each of which is ideally suited to remove at least one type of organic matter from wastewater.\",\n \"By way of example, BCR 110 uses heterotrophic bacteria (e.g., Achromobacter, Alcaligenes, Arthrobacter, Cirtomonas, Flavobacterium, Pseudomonas, and Zoogloea) for removal of BOD.\",\n \"BOD is created by any matter containing a carbon molecule normally present in wastewater and that is generated from any one of human waste, food waste, animal waste, and plant waste.\",\n \"Blower 204 is effective in providing oxygen to microorganisms in wastewater.\",\n \"Size of bubbles formed in wastewater from pumping air and the amount of air pumped dictate the amount of oxygen dissolved in wastewater.\",\n \"Those skilled in the art will recognize that small bubbles may be twice as efficient at transferring oxygen because they provide greater surface area of air per mass of air.\",\n \"Bubbles also mix wastewater inside the BCR to ensure that nutrients in wastewater are in constant contact with the bacteria that consumes them.\",\n \"The presence of biological chips provides a high surface area inside the reactor to which the microorganisms may affix.\",\n \"By way of example, the ratio of surface area inside the BCR to volume of BCR is between about 32 square feet per cubic foot and about 130 square feet per cubic foot.\",\n \"Preferably, however, the ratio of surface area inside the BCR to volume of BCR is about 73.5 square feet per cubic feet.\",\n \"High surface area combined with high oxygen concentration aide the metabolic rates of microorganisms.\",\n \"The affixed microorganisms quickly remove all available food in the form of organic particulate matter (which contribute to BOD) from the reactor and leave a situation of high metabolic rates and low amounts of food (i.e., there is a low ratio of food to microorganism).\",\n \"Over a period of time, most solids in the reactors continue to be active and remove more BOD from the influent water.\",\n \"Eventually, as more and more of the food is depleted inside the reactor, the microorganisms die from starvation.\",\n \"BCR 112 is preferably designed to contain at least one type of microorganism, which removes at least one type of organic matter that is particularly difficult to remove from the wastewater in BCR 110 or requires additional processing time, i.e., above and beyond the processing time in BCR 110.According to the present teachings, it is also possible to have additional BCRs, in addition to BCRs 110 and 112, to facilitate effective organic matter removal.\",\n \"By way of example, an initial step of nitrification is carried out in BCR 112 by autotropic bacteria Nitrosomonas, which converts ammonia to nitrite, despite the fact that some nitrifying bacteria exist in BCR 110.A third BCR (not shown in FIG.\",\n \"1A to simplify illustration) may be used for a subsequent step of nitrification using autotropic bacteria Nitrobacter.\",\n \"In preferred embodiments of the present teachings, BCRs 110 and 112 are about 7 feet long, 10.5 feet wide, and 8 inches in height.\",\n \"Temperature inside BCRs is preferably between about 15° C. and about 33° C., and the hydraulic residence time is preferably about 8 hours.\",\n \"According to one embodiment of the present teachings, BCRs are about 40% filled with small biorings, have 133 cubic feet per minute of diffused air flowing through it during operation, and use 6 ounces of defoaming agent per day.\",\n \"In cold climates, where heat dissipation is relatively high, it is preferable to keep substrate levels high to carry out nitrification effectively.\",\n \"The term “high substrate levels” means keeping a certain level of biological matter (sludge) inside the BCR to maintain its thermal mass and avoid wide temperature swings inside the BCR and/or also means keeping the bacteria count high to accommodate the greater die-off rate when temperatures drop.\",\n \"The present teachings use of a BCR, individually or in combination with other BCRs, represent an active process because it is provides air and constantly places bacteria in contact with nutrients through circulation of wastewater to effectively encourage nutrient uptake.\",\n \"Furthermore, the surface area inside the BCR is also optimized for removal of organic waste.\",\n \"Aerobic sludge digester 114 is one type of BCR, except that it is designed to remove sludge.\",\n \"In other words, digester 114 contains microorganisms that are known to consume, and therefore remove, sludge.\",\n \"Although the BCRs and aerobic sludge digesters remove organic matter and lower the BOD, they leave wastewater rich with nitrates from the endogenous decay of microorganisms that have run out of food source.\",\n \"To this end, previously described DAF tank 106 and a second SRT, shown as SRT 116 in FIG.\",\n \"1A, are used to remove dead microorganisms.\",\n \"To remove dead microorganisms, DAF tank 106 is provided with another chamber, separate from the chamber which is used to remove from wastewater solids that are not dead microorganisms.\",\n \"IIRAP 118 is used in system 100 to remove nutrients from wastewater.\",\n \"FIG.\",\n \"3 shows HRAP 300, according to one preferred embodiment of the present teachings.\",\n \"HRAP 300 includes a tank 302 containing algae 308.A spectrum of radiation 306 operates at wavelengths that range from about 102 nm and 106 nm.\",\n \"This spectrum of radiation is preferably disposed at a location that is between about ⅓ and about ½ the depth of HRAP 300.At the bottom of tank 302, a solid waste layer 304 accumulates which may ultimately be removed.\",\n \"A hydraulic pump and a paddle (both not shown to simplify illustration) are preferably provided in HRAP 300 for stirring and aeration of wastewater.\",\n \"Aeration and stirring facilitates driving up the dissolved oxygen level in wastewater to promote algae growth.\",\n \"Tank 302 is preferably maintained at a temperature that is between about 21° C. and 35° C. FIG.\",\n \"4 shows a perspective view of HRAP 300, in accordance with one preferred embodiment of the present teachings.\",\n \"Inside HRAP 300 wastewater is preferably guided through a channel, which allows the water to traverse back and forth along a length of tank 302.The channel carves out a hydraulic path for wastewater and is preferably serpentine in shape.\",\n \"HRAP may have any dimensions that effectively remove nutrients from wastewater.\",\n \"The present teachings recognize, however, that nutrient load and flow rate of wastewater drive HRAP dimensions.\",\n \"By way of example, HRAP has a length of about 24 feet, a width of about 77 feet, and a height of about 4 feet.\",\n \"IIRAP preferably provides a surface area that is between about 1000 square feet and about 50,000 square feet and, more preferably, about 1848 square feet for wastewater treatment.\",\n \"The channel length is preferably between about 200 feet and about 3000 feet.\",\n \"Inside the channel of HRAP, wastewater moves at a velocity of 10 inches per second and has a residence time of about 72 hours.\",\n \"HRAP primarily uses algae to remove nitrates and phosphates from wastewater.\",\n \"Growth rate of algae is dictated by available oxygen, temperature, light, and nutrients.\",\n \"Conventional algal ponds are very shallow because they facilitate introduction of oxygen and penetration of light to promote algae growth.\",\n \"Unfortunately, for processing relatively large volumes of wastewater, conventional algal ponds are very large, i.e., they are typically measured in hectares.\",\n \"The present teachings preferably use an HRAP, which is deeper and not so spread out.\",\n \"In preferred embodiments of the present teachings, it both aerates and stirs wastewater to effectively introduce oxygen.\",\n \"Furthermore, a radiation source inside the HRAP effectively facilitates penetration of light through greater depths of wastewater.\",\n \"As a result, HRAPs according to the present teachings may occupy as little as 160 square meters for 120-cubic-meters-per-day flow systems.\",\n \"Preferably contemporaneous with above-described treatment of wastewater, the present teachings also treat byproducts resulting from wastewater treatment.\",\n \"To this end, FIG.\",\n \"1B shows a system 140, according to one embodiment of the present teachings, for separating methane gas from other components of biogas that are produced after anaerobic digestion in wastewater.\",\n \"Although this system and other such systems which process byproducts of wastewater treatment may function either in a contemporaneous or non-contemporaneous manner relative to wastewater treatment, in preferred embodiments, inventive systems and methods process the byproducts in a contemporaneous manner to increase throughput and avoid byproduct build-up.\",\n \"System 140 includes a tank 126, preferably a scrubber, for removal of methane 132 so that it may subsequently be used as energy source (described below with reference to FIG.\",\n \"5).\",\n \"Tank 126 includes a first inlet for receiving a stream of water (e.g., a portion of treated water 125 from maturation pond 122 of FIG.\",\n \"1A), a first outlet for dispensing an effluent water stream 130 having dissolved therein certain components of biogas, a second inlet for receiving biogas 128 produced after anaerobic digestion, and a second outlet for methane exhaust 132.As shown in FIG.\",\n \"1A, methane, one component of biogas, is a residual gas as it is not soluble in water.\",\n \"Tank 126 may receive a water stream from any source of water or pure water.\",\n \"In the interest of water conservation, the present teachings recognize that a portion of treated wastewater resulting from wastewater treatment may be used for processing byproducts of wastewater treatment.\",\n \"Tank 126 preferably comes equipped with a bubbler 129 to produce bubbles.\",\n \"Specifically, bubbler 129 introduces biogas 128 inside a tank full of water in the form of micro-bubbles.\",\n \"The bubbles provide a large surface area between the biogas/water interface to facilitate dissolving certain soluble biogas components in water.\",\n \"Residual methane gas exits tank 126 and is further processed as described below in system 170 of FIG.\",\n \"5.FIG.\",\n \"5 shows a system 170, according to one embodiment of the present teachings, for converting methane exhaust into electricity and for converting residual gases resulting from an electricity generator to a simpler, less complicated molecular form that may be used by HRAP 118 of FIG.\",\n \"1A to foster growth of algae, which is useful for producing, among other things, biofuels.\",\n \"System 170 includes an electrical generator 150 and a tank 160, which is preferably a scrubber.\",\n \"Electrical generator 150 uses methane exhaust 132 (generated inside tank 126 of FIG.\",\n \"1B) to generate electricity and a produce a gaseous mixture 152 (e.g., including at least one of CO2, SOx, and NOx), which are fed into a tank 160.According to FIG.\",\n \"5, a portion of treated water 125 from maturation pond 122 of FIG.\",\n \"1A enters tank 160 such that it contacts gaseous mixture 152 of tank 160.A bubbler 156, similar to bubbler 129 of FIG.\",\n \"1B, ensures that the gaseous mixture in the form of micro bubbles contacts water to facilitate dissolving components of the gaseous mixture in water.\",\n \"As a result, a certain amount of the gaseous components of mixture 152 dissolves in the treated water to form water 162 that is enriched with aqueous components (i.e., predominantly at least one of CO2, SOx, and NOx).\",\n \"As shown in FIG.\",\n \"5, this gas-enriched water stream 162 is advanced to HRAP 118 of FIG.\",\n \"1A, where algae production is promoted by the dissolved gaseous components in water.\",\n \"The residual gases, which include remaining amounts of at least one of CO2, SOx, and NOx that did not dissolve in treated water, are recycled back to tank 160 via line 154 for further treatment.\",\n \"The goal of the recycling feature of FIG.\",\n \"1B is to ultimately dissolve all of CO2, SOx, and/or NOx gases in water and advance these gases to HRAP 118 of FIG.\",\n \"1A to promote algae growth.\",\n \"FIG.\",\n \"1C shows a system 180, according to one embodiment of the present teachings, for processing gas (i.e., predominantly ammonia gas and sulfur gas) produced by BCR 110 of FIG.\",\n \"1A.\",\n \"According to this figure, gaseous byproducts resulting from aerobic digestion of wastewater that is carried out in BCR 110, are transported to a tank 140, preferably a scrubber, for processing.\",\n \"Like tank 160 of FIG.\",\n \"5 and tank 126 of FIG.\",\n \"1A, tank 140 of FIG.\",\n \"1C comes equipped with bubbler 139, which introduces the gas produced in BCR 110 in the form of micro bubbles through the tank full of treated water to facilitate dissolving in water of those components of the gaseous byproducts that are soluble in water.\",\n \"Tank 160 includes a first inlet for receiving water and a first outlet for dispensing water, which is enriched with at least a soluble amount of gaseous components that dissolve.\",\n \"In preferred embodiments of the present teachings, the water is treated water 125 from maturation pond 122 of FIG.\",\n \"1A.\",\n \"However, it is possible to so treat the gaseous byproducts with a water stream obtained from any source.\",\n \"Tank 140 has a second inlet for receiving gas from BCR 110 and a second outlet for dispensing the residual gas that does not dissolve in water.\",\n \"An ammonia concentration sensor 182 is located downstream from tank 140 and is capable of controlling the flow of effluent stream from tank 140 to either HRAP 118 or back to BCR 110.To this end, ammonia sensor 182 is communicatively coupled to two different valve assemblies 184 and 186 via control lines 188 and 190, respectively.\",\n \"When ammonia concentration sensor 182 detects ammonia concentration in the effluent stream of tank 140 to be either equal to or greater than a predetermined concentration value, sensor 182 activates valve assembly 184 to convey an effluent stream of tank 140 to BCR 110 for further treatment.\",\n \"In the alternative, when sensor 182 detects ammonia concentration in the effluent stream to be less than the predetermined concentration value, sensor 182 activates valve assembly 186 to convey the effluent stream to HRAP 118.In preferred embodiments of the present teachings, the value of predetermined ammonia concentration lies in a range that is between about 0 ppm and about 10 ppm, depending primarily on the concentration of ammonia in a feed stream that is being reduced by oxidation, e.g., in the BCR reactor.\",\n \"An effluent stream with low ammonia concentration suggests nitrogen is present in the effluent stream in a less complex form which is useful for promoting algae growth in HRAP 118.In contrast, a high ammonia concentration suggests that the effluent stream does not have sufficient amount of nitrogen in simple form to facilitate algae growth in HRAP 118.Those skilled in the art will recognize that although system 180 is shown in connection with BCR 110, a similar system could be used to process the gas emanating in BCR 112 of FIG.\",\n \"1A.\",\n \"Regardless of whether gas emanating from BCR 110 or BCR 112 is processed as described above, if the concentration of ammonia in the effluent stream of a scrubber, for example, is greater than or equal to a predetermined concentration value, then that effluent stream is sent hack to the BCR so that the dissolved aqueous ammonia in the effluent stream may be broken down to a simpler form which is ultimately useful to promote algae growth in HRAP 118.Similar to ammonia gas, sulfur is another gaseous byproduct of aerobic digestion carried out in BCR 110 or BCR 112 of FIG.\",\n \"1A.\",\n \"Instead of or in addition to using an ammonia concentration sensor, system 180 of FIG.\",\n \"1C may include a sensor for detecting the concentration of sulfur gas (not shown to simplify illustration) if the presence of sulfur gas is expected or suspected as a byproduct of aerobic digestion.\",\n \"Those skilled in the art will recognize that the valve assemblies, similar to those shown in connection with the ammonia concentration sensor, may be used in conjunction with the sulfur concentration sensor.\",\n \"Because sulfur naturally dissipates faster relative to ammonia, it is not necessary in preferred embodiments of the present teachings to monitor the sulfur concentration in the same way as the ammonia concentration.\",\n \"In even more preferred embodiments of the present teachings, only the ammonia concentration is measured and so long as that concentration is less than a predetermined value, it is safe to assume that the sulfur concentration is also sufficiently low to advance the effluent stream from tank 140 to HRAP 118.In preferred embodiments of the present teachings, electrical generator 150 is commercially available from General Electric, Inc.'s Jenbacher gas engine division located in Jenbach, Austria.\",\n \"However, other electrical generators, which use methane to generate electricity will work also.\",\n \"In preferred embodiments of the present teachings, tank 126 (in system 140 of FIG.\",\n \"1B), tank 140 (in system 180 of FIG.\",\n \"1C), and tank 160 (system 170 of FIG.\",\n \"5) are large enough to hold at least a volume of liquid that is between about 380 liters and about 38000 liters.\",\n \"Wastewater treatment according to present teachings has many advantages over the conventional wastewater treatment technology.\",\n \"At a minimum, conventional wastewater treatment processes release noxious byproducts of anaerobic and aerobic digestion into the atmosphere, some of which are believed to contribute to the greenhouse effect.\",\n \"In sharp contrast, the present teachings offer novel systems and methods to process these byproducts to generate clean energy and promote production of useful downstream products.\",\n \"In preferred embodiments of the novel systems and methods of the present teachings, a portion of the treated wastewater is used to process the byproducts as mentioned above.\",\n \"It is counter to conventional wisdom that treated or purified water obtained from wastewater treatment should be used to treat environmentally harmful byproducts because after putting a substantial amount of energy in treating wastewater, conventional wastewater techniques teach away from wasting that energy by contaminating that treated water.\",\n \"As a result, conventional wastewater treatment processes fail to recognize, among other things, that a portion of the treated water may be used to convert byproducts of wastewater treatment into clean energy.\",\n \"The present teachings provide a substantially closed system that treats wastewater and recycles a portion of that treated wastewater to convert noxious byproducts of wastewater treatment into useful energy.\",\n \"By way of example, if the closed system is implemented on a farm, then the wastewater generated at the farm may be treated and at the same time be used to produce clean energy for the farm.\",\n \"In other respects unrelated to treatment of byproducts, at a minimum, conventional wastewater treatment processes fail to recognize: (i) that decomposition of organic matter depletes soluble oxygen in wastewater constantly during various treatment steps; (ii) the need to substantially maintain the level of dissolved oxygen in wastewater at various stages is important for effective treatment; and (iii) that failure to substantially maintain level of dissolved oxygen and lower solid content through each stage of wastewater treatment causes a reversible reaction which reverses the treatment accomplished in previous treatment steps.\",\n \"To this end, various steps in preferred embodiments of the present teachings recognize the need to drive down BOD, solid content, and nutrient level and maintain or increase level of dissolved oxygen in wastewater.\",\n \"In preferred embodiments of the present teachings, wastewater undergoes different types of treatment.\",\n \"By way of example, BOD-creating solids are removed first.\",\n \"Then, the bacteria consume the organic matter.\",\n \"Next, nutrients present in wastewater are removed.\",\n \"After performing a first type of treatment, however, the present teachings recognize the need to stabilize the wastewater before advancing it to a second type of treatment.\",\n \"Stabilizing involves preventing a meaningful change in certain important properties of wastewater, e.g., ROD level, dissolved oxygen level, solid content level, and nutrient level, which are susceptible to changing to undesired values by a reversible reaction.\",\n \"Specifically, by lowering BOD levels and solid content and increasing or substantially maintaining dissolved oxygen levels in wastewater throughout the various stages, the present teachings effectively transition from one treatment type to another, without suffering from drawbacks of a reversible reaction.\",\n \"In accordance with one embodiment, the inventive process using system 100 of FIG.\",\n \"1A may begin when a treatment system 100 receives wastewater for treatment directly from an anaerobic tank (e.g., anaerobic tank 102 of FIG.\",\n \"1A).\",\n \"Inside anaerobic tank 102, complex organic material is broken down into smaller constituent organic material by anaerobic bacteria under anaerobic conditions.\",\n \"By way of example, inside anaerobic tank 102, a temperature may be a value that is between about 30° C. and 40° C., a pressure that is about 1 atmosphere, and a volume that is between about 10 gallons per minute and about 15,000 gallons per minute.\",\n \"The volume of the tank is completely scalable and may be higher than 15,000 gallons per minute so long as the necessary amount of equipment is used to process a large amount of liquid in parallel.\",\n \"In the anaerobic tank, the wastewater is treated with microorganisms that carry out anaerobic digestion, causing the release of biogas 128 that is captured atop an anaerobic tank and delivered to a tank (e.g., tank 126 of FIG.\",\n \"1B), which is preferably a scrubber and is capable of separating methane from the other components of biogas.\",\n \"The wastewater is then immediately advanced for solid removal as one type of treatment.\",\n \"In a preferred embodiment of the present teachings, solid removal is carried out methodically in different steps.\",\n \"It is noteworthy that in this embodiment, not only are solids removed at different steps, but the inventive process is designed to substantially maintain the level of dissolved oxygen in wastewater during these steps to avoid a reversible reaction.\",\n \"Solid removal preferably begins with removal of relatively large solids from wastewater using a mechanical technique.\",\n \"By way of example, a solids separator such as the one shown in FIG.\",\n \"1A is preferably used for pressing wastewater containing solids because it also introduces air into the wastewater during the pressing action.\",\n \"As a result, pressing not only removes large solids from wastewater but also maintains the level of dissolved oxygen in wastewater.\",\n \"At this early stage of solid removal, an aerobic process ensures a natural biological degradation and purification process in which bacteria that thrive in oxygen-rich environment break down and digest the organic matter.\",\n \"Maintaining oxygen levels during solid removal ensures that such bacteria do not die off and that level of BOD-contributing solids and solid content in wastewater does not increase.\",\n \"Undesired increase in BOD-contributing solids at this stage would defeat the ultimate purpose of removing the BOD-contributing solids in this step.\",\n \"In other words, during a single treatment step, lowering solid content, lowering BOD level, and substantially maintaining or increasing level of dissolved oxygen in wastewater prevents a reversible reaction that increases BOD, solid content, and/or lowers level of dissolved oxygen in wastewater.\",\n \"After removing large solids, preferred embodiments of the present teachings focus on the removal of medium-sized particles using small air bubbles.\",\n \"In this treatment step, medium-sized.\",\n \"solids are carried by an upward motion of air bubbles and removed as explained previously.\",\n \"As a result, bubbles remove BOD-contributing solids, lower solid content, and introduce oxygen simultaneously to substantially maintain or increase a level of dissolved oxygen in wastewater.\",\n \"The advantages of lowering BOD and solid content, and at the same time substantially maintaining or increasing a level of dissolved oxygen in wastewater realized in the previous step, are also realized in this step.\",\n \"For removal of finer solids from wastewater, the inventive process in a preferred embodiment moves to a tank, such as SRT 108 as shown in FIG.\",\n \"1A.\",\n \"This tank also stabilizes the wastewater before removal of organic matter commences.\",\n \"Specifically, the tank is designed to remove fine solid particles using a screen when diffused airflow is used inside the tank.\",\n \"Such air flow provides cleaning action to remove the solid build up on the screen and introduces oxygen into wastewater.\",\n \"The advantages of lowering BOD and solid content in wastewater, and at the same time substantially maintaining or increasing level of dissolved oxygen in wastewater realized in the previous steps, are also realized in this step.\",\n \"Next, the inventive process preferably moves to removal of organic matter as another type of treatment.\",\n \"In this stage of treatment, preferably in a BCR, such as the one shown in FIG.\",\n \"1A, microorganisms in the presence of biological chips consume organic matter.\",\n \"The microorganisms release gas containing ammonia and sulfur.\",\n \"Various steps of the present teachings (described below with reference to FIG.\",\n \"1C) provide a means to clean this gas with recycled wastewater 125.Consumption of organic matter by microorganisms is enhanced by the presence of a blower, which introduces oxygen into wastewater, increasing level of dissolved oxygen in wastewater.\",\n \"With removal of organic matter, wastewater has lower BOD level and solid content and increased level of dissolved oxygen.\",\n \"Microorganisms after consuming a substantial amount of organic material, however, die off and increase both BOD level and solid content.\",\n \"If the dead microorganisms are not timely removed, level of dissolved oxygen in wastewater will drop and a reversible reaction will increase BOD level and solid content in wastewater.\",\n \"As a result, in the next treatment step, the present teachings offer provisions to remove dead microorganisms from wastewater.\",\n \"To this end, preferably, first anaerobic treatment and then an aerobic treatment is used.\",\n \"It is noteworthy that in preferred embodiments of the present teachings, wastewater at this stage is subjected to anaerobic digestion for a second time.\",\n \"In the anaerobic treatment at this stage, preferably an SRT is sealed off to make sure that all aerobic microorganisms die off.\",\n \"At the same time, using screens inside the SRT, dead microorganisms are removed using screens inside the SRT.\",\n \"This lowers both BOD level and solid content in wastewater.\",\n \"But, before wastewater may advance to the next stage, the present teachings realize that level of dissolved oxygen in wastewater should increase.\",\n \"In the next step, aerobic treatment is preferably carried out using a DAF tank such as the one shown in FIG.\",\n \"1A.\",\n \"Diffused airflow inside the DAF tank raises level of dissolved oxygen and removes residual solids.\",\n \"Now, wastewater having lower BOD level and solid content and higher level of dissolved oxygen is ready for the next stage of treatment.\",\n \"In the next stage, wastewater is treated in algal pond, preferably an HRAP such as the one shown in FIG.\",\n \"1A, to effectively remove nutrients from wastewater.\",\n \"Nutrient removal from wastewater is carried out by algae, which in the presence of an operating radiation source effectively consumes nutrients.\",\n \"Algae also boost level of dissolved oxygen in wastewater.\",\n \"However, level of dissolved oxygen in wastewater may not be high enough to meet the requirement of discharge to environment.\",\n \"It is important to recognize that if after anaerobic treatment aerobic treatment did not follow, then wastewater with high concentration of ammonia, as opposed to nitrates or nitrogen, would have entered the HRAP posing a risk of killing algae.\",\n \"Thus, anaerobic treatment followed by aerobic treatment ensures that wastewater is prepared for nutrient removal in the subsequent steps.\",\n \"In the next treatment steps, dissolved oxygen level in wastewater is raised to allow discharge to environment.\",\n \"Preferably a DAF tank is used to provide diffused air flow for raising level of dissolved oxygen and removing algae and other solids from wastewater.\",\n \"Solid removal lowers BOD level and solid content in wastewater.\",\n \"Then, for removal of finer particles, wastewater is advanced to an SRT, which uses diffused air for removal of solids from and introduction of oxygen to wastewater.\",\n \"Consequently, wastewater has the requisite high level of dissolved oxygen, lower BOD level, and solid content for discharge into environment.\",\n \"Although wastewater is now ready for discharge into environment, preferred embodiments treat this wastewater in a maturation pond where it is exposed to elements found in the environment.\",\n \"Wastewater matures and is adapted to the natural environment in the maturation pond, from where it is discharged to the environment.\",\n \"As shown in FIG.\",\n \"1A, solids removal is carried out at least partially in DAF tank 106 and SRT 108.During such solids removal, however, aerobic bacteria are typically present.\",\n \"As a result, when oxygen is added to these tanks during solids removal, these tanks are not only efficiently removing solids, but are effectively carrying out aerobic digestion on the wastewater well before that wastewater reaches the BCR reactors, where the wastewater further undergoes aerobic digestion.\",\n \"In accordance with preferred embodiments, the inventive processes on a parallel track treat the gaseous byproducts produced during wastewater treatment.\",\n \"By way of example, biogas (e.g., methane, carbon dioxide, ammonia, hydrogen, and sulfur) resulting from anaerobic digestion is delivered from an anaerobic tank to another tank, which is preferably a scrubber.\",\n \"Before biogas is conveyed to the tank, the tank is filled with water, which is preferably treated water obtained after the conclusion of a wastewater treatment process.\",\n \"Inside the tank, water contacts the biogas.\",\n \"In preferred embodiments of the present teachings, biogas is in the form of tiny micro bubbles when it contacts water.\",\n \"Biogas in bubble form provides a high surface area between the biogas/water interface to allow certain gases in the biogas mixture to dissolve in water.\",\n \"However, as methane does not dissolve in water, it exhausts from the tank.\",\n \"Instead of releasing methane exhaust into the atmosphere, as conventional processes do, the present teachings deliver methane for further processing to an electrical generator located downstream.\",\n \"From inside the tank, a stream of water, which contains certain biogas components dissolved therein, is discharged to a tank for solids removal (e.g., DAF tank 106 of FIG.\",\n \"1A).\",\n \"The methane exhaust is further processed (e.g., in system 170 of FIG.\",\n \"5) to produce electricity and other useful products.\",\n \"Specifically, methane gas is delivered to an electrical generator, which converts methane to electricity and produces other byproduct gases (e.g., at least one of CO2, SOx, and NOx).\",\n \"These gaseous byproducts are next conveyed to a tank, preferably a scrubber, where they are treated substantially similarly to the treatment of biogas as a byproduct (i.e., tiny micro bubbles of the gaseous mixture are conveyed through water to dissolve those components of the gaseous mixture which dissolve in water).\",\n \"Preferably, treated water is used to process the byproduct gas.\",\n \"Residual gas not dissolved in water is recirculated back to the tank for further processing i.e., multiple passes may be made through the tank to dissolve the residual gases in water.\",\n \"Water effluent that includes the dissolved gases is conveyed to an algal pond (e.g., HRAP 118 of FIG.\",\n \"1A) to promote algae growth.\",\n \"With regard to the energy produced by the electrical generator, the amount of energy is significant.\",\n \"By way of example, for a farm that raises dairy cattle, an electrical generator produces between about 1 and about 5 kilowatts of electricity per day per animal.\",\n \"Processing of wastewater by aerobic digestion also produces byproducts, which are treated according to the preferred embodiments of novel systems and methods of the present teachings.\",\n \"In accordance with one preferred embodiment, the inventive processes may begin when byproduct gas is received into a tank, preferably a scrubber, after wastewater has undergone aerobic digestion (e.g., in BCRs 110 and 112).\",\n \"Byproduct gas (e.g., shown denoted by reference numeral 142 of FIG.\",\n \"1C) of aerobic digestion includes at least one of ammonia gas and sulfur gas.\",\n \"Before the byproduct gas is received, however, the tank is filled with water, which is preferably treated wastewater.\",\n \"In preferred embodiments, byproduct gas processed according to the present teachings is introduced in bubble form.\",\n \"A certain amount that is soluble of certain components of the byproduct gas dissolve in water and the remaining, undissolved amounts or components, such as residual ammonia gas or residual sulfur gas, are recycled back to the tank further processing (i.e., for further attempts to dissolve the residual ammonia gas and sulfur gas in water in subsequent contact cycles in the tank).\",\n \"The resulting effluent stream enriched with the soluble byproduct gas components is discharged from the tank and processed depending on the concentration of aqueous ammonia and sulfur in the water stream.\",\n \"Using an ammonia concentration sensor, the concentration of ammonia in the wastewater is determined.\",\n \"If the effluent contains ammonia in a concentration that is greater or equal to a predetermined concentration value, then the ammonia is typically sent back to the BCR reactor, from where the byproduct gas had originated.\",\n \"In this BCR, the residual ammonia gas undergoes further processing so that it is reduced to simpler molecular forms, such as nitrates, nitrites, or nitrogen, which are useful for algae growth (e.g., in HRAP 118 of FIG.\",\n \"1A).\",\n \"If, however, the concentration of ammonia is sufficiently low, i.e., below the predetermined concentration value, then the effluent stream is considered to have simpler forms of nitrogen which are useful for algae growth.\",\n \"Accordingly, effluent streams with such low concentrations of ammonia are advanced to an algal pond (e.g., in HRAP 118 of FIG.\",\n \"1A).\",\n \"In other preferred embodiments of the present teachings, the concentration of sulfur is similarly discerned.\",\n \"If the sulfur concentration sensor detects the concentration of sulfur gas to be greater than or equal to a predetermined concentration value, then the effluent stream is returned back to the BCR reactor, from where the byproduct gas had originated.\",\n \"In this BCR, the residual sulfur gas undergoes further processing so that it is consumed if not in the first pass back to the BCR, then in the subsequent ones.\",\n \"Alternatively, if the sulfur concentration detects the concentration of sulfur gas to be less than the predetermined concentration value, then the effluent stream advances to the algal pond.\",\n \"In light of the above disclosure, those skilled in the art will recognize that in preferred embodiments of the present teachings, the effluent stream of the tank (e.g., a scrubber) are only advanced to an algal pond when both concentration of aqueous ammonia and sulfur gas are below their respective predetermined concentration values.\",\n \"However, compared to ammonia, sulfur is known to dissipate relatively quickly and, therefore, in preferred embodiments of the present teachings, only the concentration of ammonia in the effluent stream is monitored as described above.\",\n \"FIG.\",\n \"6 shows a system 600, according to one preferred present arrangement, for converting solid byproducts of wastewater treatment into a plant life enhancing product, e.g., fertilizer, biocide, pesticide, and/or agricultural feed.\",\n \"System 600 includes an anaerobic feed tank 602, a solids separator 604, a DAF tank 606, an SRT #1 608, a BCR #1 610, a BCR #2 612, an aerobic sludge digester 614, an SRT #2 616, an HRAP 618, and an SRT #3 620, each of which is substantially similar to their counterparts, anaerobic feed tank 102, solids separator 104, DAF 106, SRT #1 108, BCR #1 110, BCR #2 112, aerobic sludge digester 114, SRT #2 116, HRAP 118, and SRT #3 120, respectively, in system 100 of FIG.\",\n \"1A.\",\n \"System 600 further includes an intermediate blender 660, that receives and blends different types of solid byproducts of wastewater treatment, i.e., anaerobically activated coarse solids 650, anaerobically activated medium-sized solids 624, and/or anaerobically activated fine solids 652, produced from solids separator 604, DAF tank 606, and SRT #1 608, respectively, to form an anaerobically activated organic residue 662.Preferably, these various-sized solids primarily include fibrous, cellular material (e.g., lignin, cellulose, hemicellulose) that is broken down in the above-mentioned components.\",\n \"System 600 further includes a blender 664 that receives and mixes anaerobically activated organic residue 662 from blender 664 with one or more of other solid byproducts of wastewater treatment, i.e., aerobically activated organic residue 627, dead microorganisms 654, algae-enriched slurry 656, and/or algae 658, from aerobic sludge digester 614, SRT #2 616, HRAP 618, and SRT #3, respectively, to form a slurry 666.The present arrangement also optionally includes a dryer 668 capable of drying slurry 666, and a pelletizer 670 capable of pelletizing the dried product received from dryer 668.Anaerobic feed tank 602 is designed to receive wastewater, which includes agricultural residue (e.g., biomass and manure), and treats the wastewater under anaerobic conditions.\",\n \"Inside anaerobic feed tank 602, among other things, complex organic material from agricultural residue is digested into smaller constituent organic material by anaerobic bacteria.\",\n \"Anaerobic feed tank 602 then delivers the resulting anaerobically activated slurry 632 to solids separator 604 for further treatment.\",\n \"Solids separator 604 separates anaerobically activated coarse solids 650 from anaerobically activated slurry 632, using mechanical techniques, to form an anaerobically activated slurry depleted of coarse solids 634.Anaerobically activated coarse solids 650 have an average particle size that is greater than about 150 pm.\",\n \"As shown in FIG.\",\n \"6, once separated from treated wastewater, anaerobically activated coarse solids 650 are delivered to intermediate blender 660 for blending with other types of solid byproducts.\",\n \"Also as shown in FIG.\",\n \"6, anaerobically activated slurry depleted of coarse solids 634 is then delivered to DAF tank 606 for further treatment.\",\n \"DAF tank 606 separates anaerobically activated medium-sized solids 624 from anaerobically activated slurry depleted of coarse solids 634 to form an anaerobically activated slurry depleted of medium-sized solids 636.To facilitate their removal, anaerobically activated medium-sized solids 624 are carried by an upward motion of air bubbles introduced into DAF tank 606.DAF tank 606 removes medium-sized solids from wastewater, which have an average particle size that ranges from about 25 μm to about 150 μm.\",\n \"According to FIG.\",\n \"6, separated, anaerobically activated medium-sized solids 624 are delivered to intermediate blender 660 for blending with other types of solid byproducts.\",\n \"Also, as shown in FIG.\",\n \"6, anaerobically activated slurry depleted of medium-sized solids 636 is then delivered to SRT #1 608 for further treatment.\",\n \"SRT #1 608 separates anaerobically activated fine solids 652 from anaerobically activated slurry depleted of medium-sized solids 636 to form anaerobically activated slurry depleted of solids 638.Removal of anaerobically activated fine solids 652 is facilitated by use of a screen when diffused air flow is introduced inside the tank.\",\n \"SRT #1 601 removes solids that have an average particle size that is less than about 25 μm.\",\n \"According to FIG.\",\n \"6, anaerobically activated fine solids 652 are delivered to intermediate blender 660 for blending with other types of solid byproduct.\",\n \"Also, as shown in FIG.\",\n \"6, the resulting anaerobically activated slurry depleted of solids 638 is then delivered to BCR #1 610 for further treatment.\",\n \"Intermediate blender 660 receives and blends one or more of anaerobically activated coarse solids 650, anaerobically activated medium-sized solids 624, and anaerobically activated fine solids 652, to form anaerobically activated organic residue 662.Preferably, intermediate blender 660 is designed to blend relatively fibrous solid byproducts of wastewater treatment (e.g., lignin, cellulose, and hemicellulose).\",\n \"As shown in the embodiment of FIG.\",\n \"6, intermediate blender 660 delivers anaerobically activated organic residue 662 to blender 664 for blending with other solid byproducts of wastewater treatment.\",\n \"In alternate embodiments of the present arrangement, however, a single blender is configured to blend all solid byproducts of wastewater treatment.\",\n \"BCR #1 610 treats organic matter from anaerobically activated slurry depleted of solids 638, which are typically enriched with nutrients, by aerobic digestion.\",\n \"Preferably, anaerobically activated slurry depleted of solids 638 are treated with at least one type of microorganism, which consumes organic matter.\",\n \"In one preferred embodiment of the present arrangement, the resulting wastewater slurry 640 treated in BCR #1 610 is delivered to BCR #2 612 for further treatment with one or more microorganisms that preferably consume organic matter that is particularly difficult to remove.\",\n \"The wastewater slurry 642 resulting from treatment in BCR #2 is delivered to aerobic sludge digester 614 for further treatment under aerobic conditions with one or more microorganisms that are known to consume solid sludge, i.e., accumulated organic matter, producing aerobically activated organic residue 627.Preferably, the microorganisms include at least one microorganism that converts ammonia to nitrites and at least one microorganism that converts nitrites to nitrates.\",\n \"Aerobically activated organic residue 627 is separated from treated wastewater slurry 642, producing aerobically activated slurry 644, which is in a nutrient-enriched state.\",\n \"As shown in FIG.\",\n \"6, aerobically activated organic residue 627 is then delivered to blender 664 for blending with other solid byproducts of wastewater treatment.\",\n \"Also as shown in FIG.\",\n \"6, aerobically activated slurry 644 is then delivered to SRT #2 616 for further treatment.\",\n \"Though the embodiment of FIG.\",\n \"6 shows two BCRs and one aerobic sludge digester, alternate embodiments of the present arrangement include any number of BCRs and aerobic sludge digesters.\",\n \"Likewise, other embodiments of the present arrangement include no BCRs or no aerobic sludge digesters.\",\n \"SRT #2 616 is sealed off to create anaerobic conditions during treatment of aerobically activated slurry 644, which kills substantially all of the aerobic microorganisms utilized in BCR #1 610, BCR #2 612, and aerobic sludge digester 614.Dead microorganisms 654 are then removed, preferably using screens inside SRT #2 616.As shown in FIG.\",\n \"6, dead microorganisms 654 are next delivered to blender 664 for blending with other solid byproducts of wastewater treatment.\",\n \"Also as shown in FIG.\",\n \"6, the resulting nutrient-enriched slurry 646 is delivered to HRAP 618 for further treatment.\",\n \"In preferred embodiments of the present teachings, however, nutrient-enriched slurry 646 is first delivered to DAF tank 606 for further aerobic treatment, as described above with reference to FIG.\",\n \"1A, and then delivered to HRAP 618 for further treatment.\",\n \"In HRAP 618, algae-enriched slurry 656 is separated from nutrient-enriched slurry 646 to form a nutrient-depleted slurry 648.Algae-enriched slurry 656 is delivered to blender 664 for blending with other solid waste products of wastewater treatment.\",\n \"In certain embodiments of the present arrangement, nutrient-depleted slurry 620 is delivered to SRT #3 620 for further treatment.\",\n \"In preferred embodiments, however, nutrient-depleted slurry 620 if first delivered to DAF tank 606 for further aerobic treatment, as described above with reference to FIG.\",\n \"1A, and then delivered to SRT #3 620 for further treatment.\",\n \"In SRT No.\",\n \"3 620, algae 658 are separated from nutrient-depleted slurry 648.Algae 658 are then delivered to blender 664 for blending with other solid waste products of wastewater treatment.\",\n \"Algae 658, which are rich in nutrients (e.g., nitrogen, phosphorous, and potassium), provides nutrients for use in fertilizer, biocide, pesticide, and/or agricultural feed.\",\n \"Blender 664 is any blender capable of blending solid waste products of wastewater treatment.\",\n \"Preferably, blender 664 is designed to blend relatively small products of wastewater treatment (e.g., anaerobically activated organic residue 662, aerobically activated organic residue 627, dead bacteria 654, algae-enriched slurry 656, and algae 658) to produce slurry 666.Though the embodiment of FIG.\",\n \"6 includes intermediate blender 660 and blender 664, alternate embodiments of the present arrangement include one blender that is configured to blend all solid byproducts of wastewater treatment.\",\n \"Regardless of whether a single or multiple blenders are used, the present teachings contemplate the use of an external amendment that provides additional amounts of a desired material (e.g., sulfur and nitrogen) so that a predetermined concentration of the desired material is reached in the plant life enhancing composition.\",\n \"To this end, FIG.\",\n \"6 shows that, in one embodiment of the present teachings, an external amendment 674 is connected to intermediate blender 660 via a connection 676 and is also connected to a blender 664 via a connection 678.Although it is not necessary to include the external amendment feature and its associated connections, in those instances where the concentration of a desired material needs to be supplemented in the plant life enhancing composition, external amendment 674 and at least one of the associated connections represent a preferred embodiment of the present teachings.\",\n \"Slurry 666 is comprised of one or more of anaerobically activated organic residue 662, aerobically activated organic 627, dead bacteria 654, algae-enriched slurry 656, and algae 658.Slurry 666 may be used to produce a plant life enhancing composition, e.g., fertilizer, pesticide, biocide, and/or agricultural feed, though in alternate embodiments of the present arrangement, slurry 666 may optionally be delivered to dryer 668 for drying.\",\n \"Dryer 668 is any dryer capable of drying slurry 666.The dried product resulting from dryer 668 may be used as fertilizer, pesticide, biocide, and/or agricultural feed.\",\n \"Optionally, however, the dried product may instead be delivered to pelletizer 670 for pelletizing.\",\n \"Pelletizer 670 is any pelletizer capable of pelletizing the dried product of dryer 668.In one preferred arrangement, the pellets resulting from pelletizer are used as a plant life enhancing composition, e.g., fertilizer, pesticide, biocide, and/or agricultural feed.\",\n \"FIG.\",\n \"7 shows a process 700, according to one preferred arrangement, for converting solid byproducts of wastewater treatment into a plant life enhancing product, e.g., fertilizer, biocide, pesticide, and/or agricultural feed.\",\n \"Process 700 begins with a first step 702, which includes anaerobically digesting agricultural residue to produce anaerobically activated organic residue and ammonia-enriched water.\",\n \"According to one preferred arrangement, anaerobically digesting agricultural residue to produce an anaerobically activated organic residue and an ammonia-enriched water is carried out using a series of components (e.g., anaerobic feed tank 602, solids separator 604, DAF tank 606, and SRT #1 608 of FIG.\",\n \"6) that treat organic residue under anaerobic conditions and remove various-sized solid byproducts of wastewater treatment (e.g., anaerobically activated coarse solids 650, anaerobically activated medium-sized solids 624, and/or anaerobically activated fine solids 652 of FIG.\",\n \"6) from wastewater.\",\n \"The resulting wastewater is ammonia-enriched and delivered for further treatment.\",\n \"Though not shown in FIG.\",\n \"7, prior to step 704, anaerobically activated organic waste, which is comprised of one or more of coarse, medium-sized, and fine solids, is preferably delivered to an intermediate blender (e.g., intermediate blender 660 of FIG.\",\n \"6) for blending.\",\n \"The present teachings recognize that the ratio of coarse, medium-sized, and fine solids in anaerobically activated organic waste delivered to the intermediate blender may be adjusted so as to optimize formulations for a plant life enhancing product, e.g., fertilizer, biocide, pesticide, and/or agricultural feed.\",\n \"In doing so, the present arrangement recognizes that coarse solids produced by a solids separator (e.g., solids separator 604 of FIG.\",\n \"6) are relatively less broken down than medium-sized solids produced by a DAF tank (e.g., DAF tank 606 of FIG.\",\n \"6).\",\n \"Likewise, medium-sized solids are relatively less broken down than fine solids produced by an SRT (e.g., SRT #1 608 of FIG.\",\n \"6).\",\n \"It is noteworthy that as these solids arc progressively broken down, nitrogen, in the form of ammonia, is made progressively more bioavailable.\",\n \"Accordingly, the release of nitrogen in plant life enhancing compositions, such as fertilizer, pesticide, and/or biocide is optimized by adjusting the ratio of coarse, medium-sized, and fine solids in anaerobically activated organic waste.\",\n \"By way of example, a fast-acting fertilizer, i.e., where nitrogen in the form of ammonia is readily available for uptake, may be comprised of relatively more fine solids, which contain more bioavailable nitrogen than coarse and medium-sized solids.\",\n \"Likewise, a slow-acting fertilizer may be comprised of relatively more coarse solids, which contain nitrogen that is less bioavailable and therefore released more slowly, over a longer period of time.\",\n \"Next, a step 704 includes aerobically digesting the ammonia-enriched water to produce aerobically activated organic residue.\",\n \"Preferably, aerobic digestion is carried out in a series of components (e.g., BCR #1 610, BCR #2 612, and aerobic sludge digester 614 of FIG.\",\n \"6) that facilitate removal of aerobically activated organic residue.\",\n \"Though not shown in FIG.\",\n \"7, ammonia-enriched water is preferably further treated in a series of components, including an SRT (e.g., SRT #2 616 of FIG.\",\n \"6), an HRAP (e.g., HRAP 618 of FIG.\",\n \"6), and another SRT (e.g., SRT #3 620), which facilitate removal of other solid byproducts of wastewater treatment, including dead microorganisms, algae-enriched slurry, and algae, respectively.\",\n \"Next, a step 706 includes blending the anaerobically activated organic residue with the aerobically activated organic residue to produce fertilizer.\",\n \"Though not shown in FIG.\",\n \"7, other byproducts of wastewater treatment (e.g., dead microorganisms, algae-enriched slurry, and algae) are preferably also blended with anaerobically activated organic residue to produce fertilizer.\",\n \"In preferred embodiments of the present arrangement, however, the blended product is a precursor to a plant life enhancing composition that is delivered to a dryer and a pelletizer to ultimately produce the plant life enhancing composition.\",\n \"In a similar manner to that described above with reference to step 702, the ratio of each solid waste component blended in step 706 (e.g., anaerobically activated organic residue, dead microorganisms, algae-enriched slurry, and algae) may be delivered to the blender in ratios that produce optimized formulations of fertilizer.\",\n \"In one embodiment of the present teachings, a plant life enhancing composition includes an effective amount of a bioavailable component that is available for immediate absorption by a plant and an effective amount of a precursor component, which has a more complex molecular structure than the bioavailable component.\",\n \"Over a period of time the precursor component transforms into the bioavailable component.\",\n \"In this embodiment, an effective amount of a catalyst is also provided.\",\n \"The catalyst facilitates transformation of the precursor component (i.e., more complex molecules) to the bioavailable component (i.e., less complex molecules).\",\n \"The period of time to transform the precursor component to a bioavailable component may vary depending on various factors, such as the temperature at which the plant enhancing composition is placed, amount of activating agent, such as water, and the complexity of the precursor component.\",\n \"In one preferred embodiment of the present teachings, duration is a period of time that ranges from about one day to about six months.\",\n \"An effective amount of the catalyst may be a value that ranges from about.\",\n \"0.01% (by weight of the fertilizer) to about 2% (by weight of the fertilizer).\",\n \"The catalyst may include an enzyme.\",\n \"In the presence of the enzyme, the precursor component is transformed to the bioavailable component at a rate that may be between about 3 times and about 4 times faster than a rate of transforming the precursor component to the bioavailable component in absence of the catalyst.\",\n \"In one embodiment of the present teachings, the enzyme includes at least one member chosen from a group comprising β-glucosidase, fluorescein diacetate hydrolysis, amidase, urease, phosphatase, sulfatase , endoglumayase, cellobiohydrolase, β-glucosidase cellobiohydrolase, endoxylanase, endomannanase, β-glycosidases, esterases, endochitinase, N-acetlyglucosaminidase, α-glucosidase, Mn-peroxidase, lignin peroxidase, laccase, phenoloxidase, proteases, aminopeptidases, urease, phosphomonoesterase, phospohodiesterase and arylsulfatase.\",\n \"In the plant life enhancing composition, the bioavailable component includes an effective amount of micronutrient and/or an effective amount of macronutrient to enhance plant growth.\",\n \"The effective amount of each of the micronutrient and the macronutrient is a value that may range from about 0.1% (by weight of the bioavailable component) to about 6% (by weight of the bioavailable component).\",\n \"The micronutrient preferably includes at least one member selected from a group comprising boron, cobalt, chromium, copper, fluorine, iodine, molybdenum, selenium, zinc, chlorine, iron, manganese, zinc and nickel.\",\n \"The macronutrient preferably includes at least one member selected from a group comprising nitrogen, potassium, calcium, magnesium, phosphorous, carbon and sulfur.\",\n \"The precursor component preferably includes an effective amount of non-bioavailable forms of a member chosen from a group comprising boron, cobalt, chromium, copper, fluorine, iodine, molybdenum, selenium, zinc, chlorine, iron, manganese, zinc, nickel, nitrogen, potassium, calcium, magnesium, phosphorous, carbon and sulfur.\",\n \"The effective amount of the precursor component may be a value that ranges from about 0.01% (by weight of the plant life enhancing composition) to about 10% (by weight of the plant life enhancing composition).\",\n \"In other aspects, the plant life enhancing composition of the present teachings include an effective amount of a dormant component, which, in turn, may include any one of aerobically activated organic residue 627, dead bacteria 654, algae-enriched slurry 656 and algae 658).\",\n \"In this aspect, an effective amount of a decomposed dormant component may also be present.\",\n \"The decomposed dormant component includes an output of anaerobic digestion.\",\n \"By way of example, decomposed dormant component includes anaerobically activated fine solids which may comprise any one of activated coarse solids 650, anaerobically activated medium-sized solids 624, and anaerobically activated fine solids 652.The resulting plant life enhancing composition, as discussed above, in some instances may not have a sufficient amount of a desired material.\",\n \"To this end, the plant life enhancing composition may be admixed with an effective amount of an amendment to provide a predetermined amount of one more desired materials that are inorganic or organic in nature.\",\n \"Examples of one or more of the desired materials may include sulfur and/or nitrogen.\",\n \"In another embodiment, the present teachings provide a plant life enhancing composition that includes effective amounts of each of a dormant component, a decomposed dormant component and a catalyst.\",\n \"The dormant component includes an output of aerobic digestion (e.g., aerobically activated organic residue) and the decomposed dormant component includes an output of anaerobic digestion (e.g., anaerobically activated organic residue), as discussed above.\",\n \"The catalyst facilitates transformation of the dormant component to the decomposed dormant component.\",\n \"Further, the catalyst may also transform the decomposed dormant component to a bioavailable component in the plant life enhancing composition of the present teachings.\",\n \"Effective amount of each of the dormant and the decomposed dormant component may be a value that ranges from about 0.01% (by weight of the plant life enhancing component) to about 10% (by weight of the plant life enhancing component).\",\n \"The effective amount of the catalyst is a value that may range from about 0.01% (by weight of the plant life enhancing component) to about 2% (by weight of the plant life enhancing component) and in presence of the catalyst.\",\n \"Further, the dormant component is transformed to the decomposed dormant component at a rate that may be between about 3 times and about 4 times faster than a rate of transforming the dormant component to the decomposed dormant component in absence of the catalyst.\",\n \"In one aspect, the present teachings propose that enzymes be used lo serve as catalysts, as they promote plant growth and effectively activate bacteria, which facilitates transforming the dormant component to the decomposed dormant component discussed above.\",\n \"Although illustrative embodiments of the present teachings have been shown and described, other modifications, changes, and substitutions are intended.\",\n \"Accordingly, it is appropriate that the appended claims be construed broadly and in a manner consistent with the scope of the disclosure, as set forth in the following claims.\"\n ]\n]"},"source":{"kind":"string","value":"Patent_15872036"}}},{"rowIdx":4493991,"cells":{"text":{"kind":"list like","value":[["BLOOD LANCET WITH HYGIENIC TIP PROTECTION","The invention concerns lancets with a lancet needle, the tip of the lancet needle being embedded in an elastic material.","Furthermore the invention concerns lancets where the tip of the lancet needle is surrounded by a hollow body which partially consists of an elastic material that can be pierced by the tip of the lancet needle during the lancing process and which reseals the tip of the lancet needle in the hollow body when it is retracted.","In addition the invention concerns a lancet magazine in which the lancets are accommodated in individual chambers, each chamber having an opening through which the tip of the lancet needle can pass, which is sealed by an elastic material.","Finally the invention concerns the use of an elastic material as a component of a lancet or a lancet magazine to maintain the sterility of at least the tip of a lancet needle in the unused state and to hygienically protect at least the tip of a lancet needle in the used state."],["1.Lancet magazine containing at least two lancets which each comprise a lancet needle with a tip and which are each accommodated in individual chambers of the lancet magazine that are independent of one another, each chamber having at least one opening for the tip of the lancet needle to emerge, the said opening of the chamber being closed by an elastic material such that the elastic material can be pierced by the tip of the lancet needle during the lancing process, characterized in that the elastic material tightly reseals after the tip of the lancet needle has been retracted into the chamber.","2.Lancet magazine according to claim 1, characterized in that the elastic material is a thermoplastic elastomer.","3.Use of an elastic material as a component of a lancet according to claim 1 to preserve the sterility of at least the tip of a lancet needle in an unused state.","4.Use according to claim 3, characterized in that the elastic material is additionally used to hygienically shield at least the tip of a lancet needle in an used state.","5.Use according to claim 3, characterized in that the elastic material is a thermoplastic elastomer.","6.Lancet magazine according to claim 1, wherein the chambers in the lancet magazine are disposed in a regular geometric pattern where neighboring chambers have at least one common wall.","7.Lancet magazine according to claim 1, wherein: each of the chambers has an inner wall; and each of the lancets has a lancet body that seals with the inner wall of the chamber.","8.Lancet magazine according to claim 1, wherein the chambers are arranged symmetrically around a central axis to give the lancet magazine a cylindrical shape.","9.Lancet magazine according to claim 1, wherein the chambers are arranged next to one another give the lancet magazine a cuboid shape.","10.A lancet system for piercing tissue to cause a body fluid to flow out of the tissue, the lancet system comprising: a lancing device; a plurality of lancets stored in the lancing device, each lancet including a lancet needle with a tip, wherein the tip is sharp for piercing the tissue, wherein the lancet needle is manufactured from a material that is hard enough to withstand mechanical stress without deformation during piercing of the tissue, a lancet body which completely surrounds the lancet needle at least in the area of the tip, the tip being able to move relative to the lancet body and able to protrude from the lancet body and the lancet body including an elastic material at least in the area of the tip of the lancet needle, characterized in that before its use, the tip of the lancet needle is embedded in the elastic material without a hollow space remaining, wherein the lancet body is configured to keep at least the tip of the lancet needle sterile in an unused state before use, wherein the elastic material is a thermoplastic elastomer that is configured to be pierced by the tip without damaging the tip, wherein the tip of the lancet needle has a first position in which the tip is embedded within the elastic material of the lancet body, wherein the tip of the lancet needle has a second position in which the tip protrudes from the lancet body, and the tip of the lancet needle being moveable from the first position to the second position; the lancing device configured to engage the lancets to move the tip of the lancet needle from the first position to the second position, wherein the tip is configured to pierce the lancet body when the lancing device moves the tip from the first position to the second position; wherein unused ones of the lancets are stored together with used ones of the lancets in the lancing device; and wherein the entire store of lancets are configured to be disposed of as a whole from the lancing device.","11.The lancet system according to claim 10, further comprising: the lancet needle having a drive end opposite the tip; and wherein a length of the lancet needle from the lancet body to the drive end is bare to allow the lancet needle to move relative to the lancet body.","12.The lancet system according to claim 11, wherein the drive end of the lancet needle is dull.","13.The lancet system according to claim 10, wherein the plurality of lancets are stored in a lancet magazine.","14.The lancet system according to claim 13, wherein the lancet magazine includes a plurality of chambers where the lancets are housed.","15.The lancet system according to claim 14, wherein the chambers in the lancet magazine are disposed in a regular geometric pattern where neighboring chambers have at least one common wall.","16.The lancet system according to claim 15, wherein the chambers are arranged symmetrically around a central axis to give the lancet magazine a cylindrical shape.","17.The lancet system according to claim 15, wherein the chambers are arranged next to one another give the lancet magazine a cuboid shape.","18.The lancet system according to claim 14, wherein: each of the chambers has an inner wall; and each of the lancets has a portion that seals with the inner wall of the chamber.","19.The lancet system according to claim 10, wherein the lancets are connected together to form a lancet tape.","20.The lancet system according to claim 19, wherein the thermoplastic elastomer connects the lancets together.","21.The lancet system according to claim 10, wherein the elastic material is stabilized with a stiff material.","22.A lancet system, comprising: a lancet magazine; a plurality of lancets accommodated in the lancet magazine, each of the lancets including a lancet needle with a tip, and a lancet body which completely surrounds the lancet needle at least in the area of the tip, the tip being able to move relative to the lancet body and able to protrude from the lancet body and the lancet body including an elastic material at least in the area of the tip of the lancet needle, characterized in that before its use, the tip of the lancet needle is embedded in the elastic material without a hollow space remaining, wherein the elastic material is an injection moldable material.","23.The lancet system of claim 22, further comprising: wherein for each of the lancets the tip of the lancet needle has a first position in which the tip is embedded within the elastic material of the lancet body, the tip of the lancet needle has a second position in which the tip protrudes from the lancet body, and the tip of the lancet needle being moveable from the first position to the second position; and a lancing device having a drive device engaging the lancet needle to move the tip of the lancet needle from the first position to the second position.","24.The lancet system according to claim 22, wherein the lancet magazine includes a plurality of chambers where the lancets are housed.","25.The lancet system according to claim 24, wherein the chambers in the lancet magazine are disposed in a regular geometric pattern where neighboring chambers have at least one common wall.","26.The lancet system according to claim 25, wherein the chambers are arranged symmetrically around a central axis to give the lancet magazine a cylindrical shape.","27.The lancet system according to claim 24, wherein: each of the chambers has an inner wall; and each of the lancets has a portion that seals with the inner wall of the chamber."],["