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referring now to fig1 there is shown a portion of a thin film test sampling chamber which is denoted generally by the numeral 2 . the test sample being assayed in this case is blood plasma or serum and it is being assayed for the presence of tsh ( thyroid specific hormone ). the chamber 2 has a surface or wall 4 to which a plurality of ligands 6 is affixed . in this case the ligands 6 will be specific to a first surface epitope of the tsh molecules being assayed . fig2 shows the chamber 2 after it has been filled with a mixture of the plasma being assayed and fluorescent reporter particles 8 . the particles 8 include ligands that are specific to a second epitope on the target analyte so that some of the particles will bond with target analyte molecules prior to being placed in the testing chamber 2 . fluorescent reporter particles that bond to the target analyte molecules 12 are designated by the numeral 10 . the free unbound fluorescent reporter particles are designated by the numeral 8 in fig2 . the target analytes , in this case tsh , are designated by the numeral 12 in fig2 . fig2 shows several of the captured analytes 12 and a number of the free unbound fluorescent reporter particles 8 . the unbound particles 8 tend to move in the sample 4 as indicated schematically by arrows 14 . this being the case , when the sampling chamber 2 is imaged as shown schematically in fig3 , the fluorescent signal from the captured reporter particles ( on the target analytes ) will be relatively bright in the sample , as indicated by the numeral 10 ′ in fig3 , and the fluorescent signal from the free reporter particles will be relatively dim or blurry , as indicated by the numeral 8 ′ in fig3 . thus the number of captured target analytes in the sample 4 can be easily determined by imaging the sample 4 . since the volume of the sampling chamber 2 is controlled , the volume of the sample 4 in the chamber 2 is known and the target analyte count can be measured in target analyte / sample volume units . referring now to fig4 - 6 , there is shown an embodiment of the device of this invention which is able to sample a larger volume of the sample being assayed . this embodiment includes a sample reservoir 16 in which a larger sample of the plasma or serum to be assayed is placed . the reservoir 16 can hold up to 1 ml , for example , of the sample . the reservoir 16 can have a flexible upper surface which can be depressed so as to compress the sample and pump it through the sample testing chamber component 2 of the assembly . the testing chamber 2 includes a control area 20 which is devoid of capture ligands 6 and the sampling area 2 ′. this control area is not shown to scale and is much smaller than the capture area or if desired may be connected with a diffusion barrier from the capture area , which includes the analyte capture ligands 6 . when the reservoir 16 is compressed , the sample will move in the direction of the arrows a through the sampling area 2 ′ and the control area 20 at the same time . after passing through the areas 2 ′ and 20 , the sample will be deposited in a reception reservoir 18 which may contain a sample absorbent , if so desired . fig6 illustrates the image that will be detected in the sample chamber 2 ′ after the sample has been moved there through . the image will show the bright images 10 of the captured reporter particles , and will show the dimmer and blurrier fluorescent signals 8 from the free or non - captured reporter particles . if the sample test is proven to be valid , then the control area 20 will only include the blurry fluorescent signals 8 . the inclusion of the reservoirs 16 and 18 will allow a greater amount of the sample to be assayed , and therefore can provide more valid test results . the broken line 11 in fig4 - 6 indicates an impermeable barrier between the sampling area 2 ′ and the control area 20 which prevents sample crossover between the two areas . many modifications of this invention with respect to its construction are possible within the description of the invention . they include the area of the assay chamber ranging from 1 mm 2 to 400 mm 2 , with a height of 2 microns to 10 microns . the localized bound antibodies are preferably placed in a homogeneous pattern , with the adjacent control area having antibodies with no affinity for the desired analyte , or no antibodies at all . it is the control area that is desirable to assure the absence of , or to control for nonspecific detection of , points of higher intensity that do not correspond to a labeled analyte . it is preferable to limit the diffusion of the sample from the control area to the capture area in order to obtain a more accurate volume determination of the amount of sample that is exposed to the capture antibody . it is also possible , if desired to perform as standard curve where multiple concentrations of known analyte are placed in the analysis chamber and analyzed under similar conditions . the number of detectable discrete signal areas per area imaged in the capture area minus the detectable discrete signals per area imaged in the control area are plotted against the known concentrations of analyte to obtain the standard curve . the results may be used to calculate the concentration of analyte in unknown samples that are analyzed under identical conditions as the standard curve . probe signal amplification such as rcat ( rolling circle amplification technology ) could be used in place of the nanoparticles since they have the effect of producing localized fluorescent particles . since many changes and variations of the disclosed embodiment of the invention may be made without departing from the inventive concept , it is not intended to limit the invention except as required by the appended claims .	6
the detailed description provided below in connection with the accompanying drawings is intended as a description of the present examples and is not intended to represent the only forms in which the present examples may be constructed or utilized . the description sets forth at least some of the functions of the examples and / or the sequence of steps for constructing and operating the examples . however , the same or equivalent functions and sequences may be accomplished by different examples . although the present examples are described and illustrated herein as being implemented for building construction , the techniques described are provided as examples and not limitations . as those skilled in the art will appreciate , the present examples are suitable for application in a variety of different types of construction or the like . fig1 a is a diagram showing an end view 100 a of an example fabricated timber with a 3 - dimensional view 100 b of the same example fabricated timber illustrated in fig1 b . such a timber according to this example is typically fabricated with two vertical members ( e . g ., members 110 and 120 ) of thickness t v and height h disposed on a horizontal member ( e . g ., member 130 ) of thickness t h and width w , each of the three members having substantially the same length l . in one example , the length l of the various members is from one to thirty feet , the height of the vertical members is from three to fifty inches , the width of the horizontal member is from three to thirty inches , and the thickness of the various members is from one to four inches . in other examples , the lengths l of the members may vary from one another , as may the thicknesses t v of 110 , t v of 120 , and t h of 130 . the surface measured by height h of the vertical members ( e . g ., 110 and 120 ) may represent a vertical plane of the members , and the surface measured by width w of the horizontal member ( e . g ., 130 ) may represent a horizontal plane of the member . the term “ substantially ” as used herein typically indicates “ according to plan ”, “ nominally ”, “ conventionally ”, and “ customary ” in relation to the arts of house - scale building construction as known to those of average skill in the art . the term “ from n to m & lt ; units & gt ;” as used herein ( e . g ., from one to thirty feet ) typically refers to a specific measurement based on a particular unit of measure ( e . g ., feet or inches or the like ) that is ≧ n and ≦ m . for example , eight feet is a distance in feet that is from one to thirty feet . thirty - nine feet , on the other hand , is not from one to thirty feet . one vertical member 110 is typically disposed length - wise atop the left side l of horizontal member 130 , and the other vertical member 120 is typically disposed length - wise atop the right side r of horizontal member 130 , as illustrated in fig1 b . vertical members 110 and 120 typically have substantially the same height h . each vertical member ( e . g . 110 and 120 ) sits atop the horizontal member ( e . g ., 130 ) such that its height h is at an angle that is substantially perpendicular to or at a substantially 90 degree angle to the width w of the horizontal member ( e . g ., 130 ). the length l of supported vertical member 110 typically extends down the length l of horizontal member 130 , and the length l of supported vertical member 120 also typically extends down the length l of horizontal member 130 . vertical members 110 and 120 are typically disposed length - wise atop horizontal member 130 so as to be substantially parallel with each other ( e . g ., 160 ), and to be substantially parallel with outer sides l and r of horizontal member 130 . in one example , the shape of each member may generally be described as cuboid comprising three opposing pairs of rectangular faces . in some examples , vertical members 110 and 120 are fastened to horizontal member 130 using fasteners ( e . g ., 150 ) such as nails , screws , bolts , staples , pins , dowels , pegs , spikes , ties , strapping , adhesive , or the like . in one particular example , fastener 150 represents conventional 16d nails every n inches on center . the term “ every n inches on center ” as used herein refers to a fastener ( e . g ., a nail ) installed so as to fasten the vertical member to the horizontal member as illustrated in fig1 a , with such a fastener installed at least every n inches along the length l of the vertical and horizontal members , each such fastener approximately centered between the inner vertical face f i of the vertical member ( e . g ., 110 and 120 ) and the outer vertical face f o of the horizontal member ( e . g ., 130 ). one example of n may be 8 . in other examples , other types or sizes of fasteners may be installed at other increments along the length l of the vertical and horizontal members . in further examples , a fabricated timber may be cast , extruded , molded , hewn , carved , cut , milled , or otherwise fabricated as a single piece rather than fabricated of separate members 110 , 120 , and 130 as shown in the examples of fig1 a and 1 b . note that the horizontal and vertical members of a fabricated timber form a channel 180 . this channel may be used for installing utilities such as electrical wires , gas and / or water lines , ducting , and the like . this channel may optionally be filled with insulation . blocking may be added at the ends to keep insulation in , or ends may be covered with plastic , cardboard , or any other suitable material or the like to retail any insulation inside the fabricated timber . the term “ blocking ” as used herein typically refers to pieces of wood or other material ( e . g ., 224 ) disposed between members ( e . g ., 110 and 120 ) to provide support , attachment sites , or brace against lateral - torsion buckling , or the like . the composition of fabricated timbers ( e . g ., 100 ) as described herein is not limited to wood , but may be plastic , fiber - cement , metal , laminated materials , composites , or the like , or any combination of such . in one example , conventional 2 × lumber has been shown to be an inexpensive and readily available choice of materials that is simple to work with and that only requires commonly - available skills and tools . the term “ 2 × lumber ” or “ two - by lumber ” as used herein generally refers to softwood or conifer sized to nominal standardized dimensions as commonly used in construction of wood - buildings and the like , where the number ‘ 2 ’ in “ 2 ×” typically refers to the nominal pre - dried 2 - inch thickness of the lumber which typically measures about 1 . 5 inches once dried . such 2 × lumber used in the construction of fabricated timbers and the like is typically kiln dried or the like . note that other types and sizes of lumber may also be used in fabricated timbers , including hardwood , rough - cut wood , or wood of thicknesses less than or greater than about 1 . 5 inches , etc . the only factor limiting the composition of a fabricated timber 100 is that it should possess certain attributes as described herein below . in the example where members 110 , 120 , and 130 are each separate members , one attribute that these members should possess is a common shrinkage characteristic . the term “ shrinkage characteristic ” as used herein refers to expected amounts and directions of shrinkage over time and / or under particular conditions for a particular material ( e . g ., wood , etc ). further , should the material from which members ( e . g ., 110 , 120 , and 130 ) are fabricated include a grain ( as with e . g ., wood , fiber - cement , etc ), the grain of each member should be oriented in substantially the same plane , such as a horizontal plane . such grain alignment may result in shrinkage over time that is relatively consistent in direction and amount between each of the members . further , any given member ( e . g ., 110 , 120 , and 130 ) may actually comprise multiple separate members of various lengths positioned end - to - end resulting in an overall length of l . the term “ grain ” as used herein typically refers to an overall direction of a pattern of fibers or the like of a material such as that from which members of a fabricated timber are comprised . the term “ fabricated timber ” as used herein refers to a statutory article ( s ) of manufacture constructed according to various example methods described herein and that is configured for possessing various attributes specified herein . the term “ fabricated timber ” does not refer to any pre - existing article ( s ) of manufacture or the like . nor does it suggest any pre - existing method ( s ) of construction or the like . in one example of a fabricated timber 100 , a vertical member ( e . g . 120 ) is disposed atop a horizontal member ( e . g ., 130 ) such that the outer portion of the vertical member overhangs the horizontal member resulting in a reveal , such as reveal r 140 . either or both vertical members may be disposed to provide such a reveal r 140 . such a reveal is typically from 0 % up to about 50 % of the thickness t v of the vertical member . such a reveal can be used for , among other things , a location for chinking or the like and / or running wiring , plumbing , and / or other utilities or the like as described below . in one example , a reveal up to ¾ inch ( about ¼ inch being preferred ) is provided for chinking or the like . the term “ reveal ” as used herein typically refers to a side of an opening between an outer surface and an inner surface . an example of such a side of an opening is provided by r 140 with respect to the outer surface of member 120 ( opposite f i ) and to the inner surface f o of member 130 . in another example of a fabricated timber 100 , a vertical member ( e . g . 120 ) is positioned atop a horizontal member ( e . g ., 130 ) such that no reveal is provided , but such that the outer face of the vertical member is substantially flush with the outer side of the horizontal member instead . such a “ no reveal ” configuration may provide for stacked timbers that have an appearance of a square log with a height that is the combined height of the stacked timbers where the horizontal interfaces between the stacked logs are dressed so as to be substantially non - visible . other “ no reveal ” configurations are also acceptable , as described below . the term “ dressed ” (“ dressing ”, “ dress ”, and the like ) as used herein typically indicates treating the outside faces of individual or stacked fabricated timbers and / or interfaces of stacked fabricated timbers to have a desired appearance . for example , it may be desirable for the outside faces of fabricated timbers to have the appearance of a square log , a peeled log , and / or a rough - hewn log , or the like . in one example , the outside faces and / or interfaces of such timbers may be distressed using a chainsaw or the like to produce an appearance of a rough - hewn log . interfaces may be filled with wood filler or the like to hide them before or after distressing . such dressing or distressing may be performed prior to timbers being stacked , or after stacking , or both . the term “ desired ” as used herein typically refers to some quality or characteristic or the like that is expected as a result of some action , design , planning , or the like . other aspects of the term “ dressed ” as used herein may include staining , tinting , painting , or otherwise coloring , finishing , and / or otherwise treating the faces , visible portions , and / or interfaces of fabricated timbers . other examples may include sealing and / or waterproofing or the like . another example may include chinking , such as with conventional chinking , cement , sand mortar , flexible vinyl chinking , or the like . conventionally , chinking is used to seal gaps between logs . in the case of fabricated timbers , chinking is primarily used for aesthetic reasons and to obtain a conventional chinked appearance or the like . various attributes that a fabricated timber 100 configured for building construction should possess include the capability of sustaining various loads including at least dead loads , live loads , and environmental loads . the noun “ building ” as used herein typically refers to a structure ( generally enclosed by walls and a roof ) constructed to provide support and shelter for an intended occupancy . the term “ occupancy ” as used herein typically refers to the purpose for which a building or other structure , or portion thereof , is used or intended to be used . the term “ load ” as used herein typically refers to forces or other actions upon a building that result from the weight of building materials and the like , building occupants and / or their possessions , objects supported by the building , environmental effects , differential movement , restrained dimensional changes , and the like . the term “ dead loads ” as used herein typically refers to substantially permanent loads such as the weight of materials of construction incorporated into a building or structure including but not limited to walls , floors , roofs , ceilings , stairways , built - in partitions , finishes , and all other similarly incorporated construction materials , and all equipment and the like affixed to the building or structure , but not including live loads or environmental loads . in one example , a fabricated timber may be configured to sustain a desired dead load of at least fifteen pounds per square foot . the term “ live loads ” as used herein typically refers to loads produced by occupancy of a building or structure that do not include dead loads or environmental loads . in one example , a fabricated timber may be configured to support a desired live load of at least thirty pounds per square foot . the term “ environmental loads ” as used herein typically refers to loads that act on a building or structure as a result of weather , topography , or other natural phenomena including but not limited to wind , snow , rain , ice , seismic activity , temperature variations leading to thermal expansion or the like , ponding , dust , fluids , floods , and lateral pressures from soil , ground water , bulk materials against the building , and the like , but not including dead loads or live loads . in one example , a fabricated timber may be configured to support a desired environmental load of at least ten pounds per square foot . in another example , a fabricated timber may be configured to support at least the desired dead load , live load , and environmental load combined . the term “ support ” as used herein with respect to a fabricated timbers typically indicates a capability to bear desired loads plus a safety factor without exceeding a yield strength of the fabricated timber or , in other words , while maintaining its elasticity . fig2 a is a diagram showing a top view of an example fabricated timber 100 . this top view shows portions of example horizontal member 130 and example vertical members 110 and 120 , as also shown in fig1 a and 1 b . also shown in fig2 a are holes ( e . g ., 220 ) of sufficient diameter to allow tie - down fasteners to pass through horizontal member 130 via the holes , as well as blocking ( e . g ., 224 ) optionally disposed on one or both sides of each hole . in one example , holes ( e . g ., 220 ) in the horizontal member are located approximately every m feet on center . the term “ every m feet on center ” as used herein refers to a hole at least every m feet along the length l of the horizontal member , each such hole approximately centered within the width w of the horizontal member ( e . g ., 130 ). in another example , holes ( e . g ., 220 ) may be provided at other increments ( e . g ., every b units ) along the length l of the horizontal member . in other examples , a fabricated timber 100 may be fabricated to include the holes ( e . g ., 220 ) and optional blocking ( e . g ., 224 ) as a single member . note that any blocking ( e . g ., 224 ) may comprise holes and / or notches ( e . g ., 225 ) to facilitate utility runs such as wiring , plumbing , etc . any one block may comprise from one to four corner notches ( only one 225 shown in fig2 b ) and / or any number of holes . generally all blocking in a fabricated timber would comprise the same hole / notch number and pattern . the size of the holes / notches ( e . g ., 225 ) is typically sufficient for desired runs of wiring , plumbing , and other utilities and the like . such blocking holes / notches ( e . g ., 225 ) may alternatively be referred to as “ blocking utility ports ”. fig2 b is a diagram showing an end view of the example fabricated timber 100 . this end view shows portions of example horizontal member 130 and example vertical members 110 and 120 , as also shown in fig1 a and 1 b . also shown in fig2 b is an end view of example blocking 224 . the composition of the blocking ( e . g ., 224 ) is typically the same as that of the fabricated timber &# 39 ; s members ( e . g ., 110 , 120 , and 130 ). further , should the material from which members 110 , 120 , 130 , and 224 are fabricated include a grain ( as with e . g ., wood , fiber - cement , etc ), the grain of each member , including blocking members ( e . g ., 224 ), should be oriented in substantially the same plane . such grain alignment may result in shrinkage over time that is relatively consistent between each of the members . in one example , blocking ( e . g ., 224 ) is attached to vertical member ( e . g ., 110 and 120 ) with fasteners ( e . g ., 226 ) as illustrated in fig2 b . in a particular example , blocking is fastened by installing two nails on each side ( e . g ., 110 and 120 ), as illustrated . alternatively or additionally , the fasteners ( e . g ., 226 ) may be installed on the bottom ( e . g ., 130 ) and / or through the bottom of a next timber ( e . g ., fig3 , 330 ), leaving the outer faces of the vertical members free from any appearance of fasteners . in another example , other types or sizes of fasteners may be installed to fasten blocking . note that the height h of the blocking is substantially the same as the height h of vertical members 110 and 120 . preferably , the blocking height is not greater than , but may be the same as or somewhat less than the height of the vertical members . fig3 is a diagram showing an example wall 300 constructed from a plurality of example fabricated timbers ( e . g ., 100 i , 100 , and 100 t ). in this example , bottom fabricated timber 100 i is attached atop foundation 310 . alternatively , the bottom fabricated timber 100 i may be positioned atop any other type of foundation suitable for a building or structure . the term “ foundation ” as used herein typically refers to the lowest load - bearing portion of a building which may comprise any suitable design and material . in this example , tie - down fasteners ( e . g ., 312 ) may be embedded in or attached to the foundation using conventional techniques . the tie - down fasteners may be comprised of multiple components ( e . g ., 312 , 320 , and 322 ) and may continue upward via holes in the horizontal member ( e . g ., 130 ) of each fabricated timber ( e . g ., 100 i , 100 , and 100 t , as well as all other fabricated timbers ). the term “ tie - down fastener ” as used herein typically refers to a fastening device or mechanism configured to secure some object ( s ) ( e . g ., a fabricated timber ( s )) against a base of some kind ( e . g ., a foundation ). in one example , bottom fabricated timber 100 i may include an optional additional member ( e . g ., 316 ) that may be fastened to the top of its horizontal member inside the timber via fasteners ( e . g ., 314 ) and further attached to the foundation via a nut and washer or the like ( e . g , 318 ), thus locking down the bottom fabricated timber 100 i to the foundation . example wall 300 extends upward to the desired height by stacking and attaching fabricated timbers one atop another starting with a bottom fabricated timber ( e . g ., 100 i ) up through the top fabricated timber ( e . g ., 100 t ). the fabricated timbers are typically stacked so as to be level horizontally and to be substantially plumb . such stacking can typically be performed by two or three people ( workers ) without the use of a crane or other heavy equipment or the like . the holes in the horizontal members may be sufficiently aligned vertically so as to allow tie - down fasteners ( e . g ., 312 & amp ; 320 ) to pass through each stacked fabricated timber while remaining substantially plumb vertically . in one example , the holes are drilled or otherwise formed by the workers as the timbers are stacked . one method of finding the correct location for each hole is to place the next timber in the desired horizontal position above the lower timber and atop the applicable and substantially plumb tie - down fasteners , beat the horizontal member of the next timber against the tops of the tie - down fasteners so as to form discernible marks on its bottom at the locations where the tie - down fasteners touch the horizontal member , and then drill or otherwise form the holes according to the marks . this method typically allows for the holes to be formed by the workers at the required locations along the horizontal member of the next timber at the job site without complex design or measurements or the like . regarding the tie - down fasteners , these fasteners may be attached to or embedded in foundation 310 at their lower ends , that extend through the courses of stacked fabricated timbers forming a wall , and that are fastened to the top of the wall thus maintaining the wall in a high degree of force over time against the foundation ( e . g ., 310 ). such tie - down fasteners may be configured to maintain the high degree of force on the wall , even in the event of shrinkage of the wall &# 39 ; s fabricated timbers and in the event that various forces are applied to the wall , including environmental forces such as wind , earthquake , shifting , flooding , and the like . in one example , each tie - down fastener may be a threaded rod , or a plurality of threaded rods ( e . g ., 320 ) coupled together by coupler nuts ( e . g ., 322 ). a bottom rod , also known as an anchor bolt , ( e . g ., 312 ) may be embedded in or otherwise attached to the building &# 39 ; s foundation ( e . g ., 310 ) via conventional means . the bottom rod may be sufficiently long to pass through the first course of fabricated timbers ( e . g ., 100 i ) and may be coupled via a coupling nut ( e . g ., 322 ) or the like to a second rod ( e . g ., 320 ) that is sufficiently long to pass through at least a second course of fabricated timbers , etc ., until a final rod or top portion of a single rod passes into and / or through a top fabricated timber ( e . g ., 100 t ). in one example , a tie - down fastener and related components may terminate against the horizontal member of the top fabricated timber . in another example , wall cap members 332 and 334 may cap the final course of fabricated timbers and allow for the tie - down fastener ( s ) to hold the stacked courses of fabricated timbers against the building foundation ( e . g ., 310 ). member 332 may be optional . member 334 may be the same width as a horizontal member ( e . g ., 130 ) or extend up to the entire width of a fabricated timber ( e . g ., 100 t ). the desired holding force may be achieved via a tensioner mechanism ( e . g ., 333 ) such as a spring or the like positioned atop a washer or plate ( e . g ., 331 ) locked in position via the rod ( e . g ., 320 ) by a nut ( e . g ., 336 ) and washer ( e . g ., 335 ) or other suitable locking device ( s ). any other suitable tensioner mechanism may alternatively / additionally be used to provide the desired force on the wall 300 . in one example ( not illustrated ), the tensioner mechanism may be installed on top of wall top cap ( e . g ., 332 and 334 ). in another example , the tensioner mechanism may be installed inside the top fabricated timber 100 t against its horizontal member as illustrated in fig3 . in one example of a wall constructed using fabricated timbers , the tie - down fasteners comprise threaded metal rods ( e . g ., 320 ) ⅝ inches in diameter joined by coupler nuts ( e . g ., 322 ) as needed , the bottom rods or anchor bolts ( e . g ., 312 ) embedded at least 6 inches in a conventional concrete foundation ( e . g ., 310 ), the tie - down fasteners spaced at least every 4 feet along the horizontal length of the wall ( e . g ., 300 ), with the top ends attached via tensioner mechanisms ( e . g ., 333 ) and associated components ( e . g ., 331 , 335 , and 336 ), and where each combination of tie - down fastener , tensioner mechanism , and associated components ( e . g ., 331 , 335 , and 336 ) has a tension capacity of at least 2 , 500 lbs . the term “ tension capacity ” as used herein is related to a material &# 39 ; s or object ( s )&# 39 ; s “ tensile strength ” and indicates a rated usage value below such a tensile strength . the term “ associated components ” as used herein typically refers to various pieces of hardware or the like required to complete , secure , and / or retain a tie - down fastener and / or tensioner mechanism , pieces of hardware such as washers , plates , nuts , pins , and the like . each course of fabricated timbers of a wall is typically attached to the previous course . fig3 shows an example of how one course can be attached to the previous course . in this example , fasteners ( e . g ., 328 and 330 ) are installed to attach a next fabricated timber that is being stacked atop a previously stacked fabricated timber . fasteners ( e . g ., 328 ) are installed so as to attach the horizontal member of the next fabricated timber to the vertical members ( e . g ., 110 and 120 ) of the previous fabricated timber ( e . g ., 110 ). further , additional fasteners ( e . g ., 330 ) may be installed so as to attach the horizontal member of the next fabricated timber to some or all of the blocking ( e . g ., 224 ) of the previous fabricated timber ( e . g ., 110 ). prior to attaching a next fabricated timber to the previous fabricated timber , gaps and the like between the two may be substantially removed . in one example , this is done by compressing the next fabricated timber against the previous fabricated timber sufficient to remove such gaps . such may be accomplished using existing tie - down fasteners to force the next fabricated timber toward the foundation until gaps and the like between the next fabricated timber and the previous fabricated timber are substantially eliminated . given a threaded rod tie - down fastener , a plate or the like may be slid down the rod against the top of the next fabricated timber , and a nut tightened against the plate to remove any gaps . then , while under compression with gaps substantially removed , the next fabricated timber may be attached to the previous fabricated timber . as one fabricated timber is stacked atop another , one or more beads of caulking and / or glue or the like may be applied . in one example , a bead of caulking may be applied along the length of a top of a fabricated timber &# 39 ; s vertical members ( e . g ., 110 and 120 ) prior to stacking another fabricated timber on top of it . such a bead may be applied along the inside and / or outside edge ( s ) of the vertical members , or along any other portion of the vertical members . one such bead may be formed from a caulking or the like that is configured to remain flexible over time , though cycles of hot and cold seasons , and to seal out moisture , bugs , air , and / or other substances and / or objects , and be further configured to maintain such a seal given settling , movement , shrinkage , or the like of the fabricated timbers . another such bead may be similarly applied that is formed of glue or construction adhesive or the like . a wall constructed of fabricated timbers that supports angled trusses may also include weight distribution members that typically approximate the shape of a right triangle , as illustrated in fig3 by element 340 . in one example , one such weight distribution member ( e . g ., 340 ) is installed atop the wall ( e . g ., 300 ) under each truss ( e . g ., 338 ). each such weight distribution member is typically disposed and configured to evenly distribute the various loads imposed by the truss across the top surface of the top course of fabricated timbers ( e . g ., 100 t ). the width of such a weight distribution member is typically about the same as the width of the wall top cap or the like that it is disposed upon . the height and hypotenuse of the weight distribution member are typically configured to support the truss by contact along the length of the hypotenuse . such a weight distribution member may be fabricated any of the materials suitable for members of a fabricated timber . fig4 is a diagram showing an example method 400 for constructing a fabricated timber . such timbers may be partially or completely assembled as pre - manufactured timbers off - site at a factory or the like , or they may be partially or entirely assembled on - site . in both cases , the basic process of construction is typically the same . block 402 typically indicates determining a total desired load plus a safety factor that the fabricated timber should support without exceeding its yield strength . the total desired load may be a minimum , and is typically comprised of a determined desired minimum dead load ( block 410 ) plus a determined desired minimum live load ( block 420 ) plus a determined desired minimum environmental load ( block 430 ). each of these determined loads may be based at least on the overall design , occupancy , and physical environment of the building . alternatively , desired average , maximum , or other loads may be used instead of desired minimum loads . block 440 typically indicates determining a composition of each of the various members of the fabricated timber . such determining may be based at least on the determined desired loads ( e . g ., block 402 ) and aspects of the design , occupancy , and physical environment of the building comprising the fabricated timber . such determining may also take into account a desired outside dressing and / or desired inside dressing of the fabricated timber . note that the various members of a fabricated timber need not be of the same composition . nor need one fabricated timber ( or various members thereof ) used in a building be of the same composition as another fabricated timber ( or various members thereof ) used in the building . block 440 also typically indicates determining a thickness of the various members of the fabricated timber , such as members 110 , 120 , 130 , and 224 . such determining may be based at least on the determined desired loads ( e . g ., block 402 ) and aspects of the design , occupancy , and physical environment of the building comprising the fabricated timber . such determining may also take into account a desired outside dressing and / or desired inside dressing of the fabricated timber . note that the various members of a fabricated timber need not be of the same thickness . nor need one fabricated timber ( or various members thereof ) used in a building be of the same thickness as another fabricated timber ( or various members thereof ) used in the building . the end result of the determinings indicated by block 440 is generally that the compositions and thicknesses of the various members of the fabricated timber have been determined . another aspect ( not explicitly indicated in fig4 ) is determining the length of the fabricated timber or each of the fabricated timbers used in a building or wall or the like . generally the length of each fabricated timber is based upon it position in a wall of a building or the like , the position of windows , doors , and other opening , the length of the wall , etc . a typical fabricated timber may generally be between approximately one and thirty feet in length . should a wall require greater lengths , two or more such fabricated timbers may be disposed end - to - end to obtain the desired overall length . yet another aspect ( not explicitly indicated in fig4 ) is determining the width of the horizontal member and the height of the vertical members of the fabricated timber or of each of the fabricated timbers used in a building or wall or the like . the width may be determined based on a desired thickness of a wall or portion thereof . the desired thickness may be based on a desired amount of insulating value , a desired appearance , or other factors that may impact the width of a wall or portion thereof . the desired height may be determined based on a desired timber height , desired appearance , desired locations of windows and / or other openings , desired wall heights , roof heights , and floor heights ( such as in multi - level structures ), and the like . block 442 typically indicates various aspects of constructing a fabricated timber . block 450 typically indicates disposing a first vertical member atop a horizontal member . in one example , the first vertical member 110 is typically disposed length - wise atop the left side l ( or the right side r ) of horizontal member 130 , as illustrated in fig1 b . the first vertical member may be disposed to provide a reveal r 140 , as illustrated in fig1 b . the first vertical member 110 may be fastened to the horizontal member 130 using fasteners installed every n inches on center or the like , and / or the horizontal member and the first vertical member may be fabricated as a single piece . the disposing of the first vertical member atop the horizontal member may take place at a job site as part of the construction of a wall of a building , or as part of a process of construction a plurality of fabricated timbers such as for later use in constructing walls or the like . block 460 typically indicates disposing a second vertical member atop a horizontal member . in one example , the second vertical member 110 is typically disposed length - wise atop the right side r ( or the left side l , whichever side the first vertical member is not disposed on ), of horizontal member 130 , as illustrated in fig1 b . the second vertical member may be disposed to provide a reveal r 140 , as illustrated in fig1 b . the second vertical member 110 may be fastened to the horizontal member 130 using fasteners installed every n inches on center or the like , and / or the horizontal member and the second vertical member may be fabricated as a single piece . the disposing of the second vertical member atop the horizontal member may take place at a job site as part of construction of a wall of a building or the like , or as part of a process of construction a plurality of fabricated timbers for later use at another site in constructing walls or the like . block 470 typically indicates forming one or more holes in a horizontal member of a fabricated timber . in one example , each hole is formed so as to enable a tie - down fastener to pass through the fabricated timber via the hole . as fabricated timbers are stacked to form a wall , holes formed in each timber are typically aligned with holes formed in any timbers above and below such that a tie - down fastener can to pass through each set of aligned holes in a substantially vertical orientation , as partially illustrated in fig3 . such holes may be formed off - site during timber fabrication in advance of wall construction , or as part of wall construction at a job site ( the location of building construction ). holes are typically formed to allow for tie - down fasteners to be installed at approximately two foot or greater intervals along the length of a wall constructed of fabricated timbers . in one example , holes are formed to allow for a tie - down fastener to be installed at approximately four foot intervals along the length of a wall . block 480 typically indicates installing a fabricated timber &# 39 ; s blocking . one example of such blocking is illustrated in fig2 a wherein a block is optionally installed on one or both sides of a formed hole . in one example , a block is installed about two to six inches on one or both sides of a formed hole &# 39 ; s center . such optional blocking is typically installed in each timber such that , when stacked , the blocking of the stacked timbers is substantially aligned vertically . that is , the optional hole blocking of one timber tends to be vertically aligned with that of any timbers above and / or below it . in another example , blocking may additionally or alternatively be installed at intervals unrelated to the location of formed holes . such blocking of stacked timbers may be installed so as to be substantially aligned vertically . as with forming holes , blocking may be installed off - site during timber fabrication in advance of wall construction , or as part of wall construction at a job site . fig5 is a diagram showing an example method 500 for constructing a wall from fabricated timbers . block 510 typically indicates attaching a timber used in constructing the wall . in one example , the first or bottom fabricated timber of a wall is typically attached to a foundation as described in connection with at least fig3 , elements 100 i and 316 . in another example , a fabricated timber that is stacked upon another fabricated timber is attached as described in connection with at least fig3 , element 328 . further , holes are typically formed in fabricated timbers so as to enable tie - down fasteners to pass through the fabricated timber via the holes . further , one or more beads of caulking or glue or the like may be applied as a part of the attaching . in one example , a bead of caulking may be applied along the length of a top of a fabricated timber &# 39 ; s vertical members ( e . g ., 110 and 120 ) prior to stacking another fabricated timber on top of it . such a bead may be applied along the inside and / or outside edge ( s ) of the vertical members , or along any other portion of the vertical members . one such bead may be formed from a caulking or the like that is designed to remain flexible over time , cycles of hot and cold , and to seal out moisture , bugs , air , and or other substances and / or objects , and be further designed to maintain a seal given settling , movement , and / or shrinkage of the fabricated timbers . another such bead may be formed from glue or construction adhesive or the like . block 520 typically indicates optionally extending a tie - down fastener ( s ) to pass through a next fabricated timber used to construct the wall . in one example , tie - down fasteners may be extended as described in connection with fig3 , elements 320 and 322 . in another example , a tie - down fastener ( s ) may not require extending , such as in the case of using full wall height tie - down fasteners . block 530 typically indicates optionally installing utilities such as electrical wires , gas and / or water lines , ducting , and the like . in one example , electrical wires , water lines , gas lines , ducting , etc , may be run horizontally through the channel ( fig1 a , 180 ) formed by a fabricated timber . such may require forming holes / notches ( e . g ., 225 ) in blocking of the fabricated timber ( s ) to allow the utilities to pass through . in another example , electrical wires , water lines , gas lines , ducting , etc , may also be run vertically from one course of fabricated timbers to another . such may require forming hole ( s ) in a horizontal member ( s ) of the fabricated timber ( s ) to allow the utilities to pass through . further , holes may be formed in vertical member ( s ) of the fabricated timber ( s ) to allow the utilities to be accesses from the outside surface ( s ) of the fabricated timber ( s ). such holes may be formed to allow for outlets , valves , vents , receptacles , etc . block 540 typically indicates optionally installing insulation . in one example , insulation is installed in the channel ( fig1 a , 180 ) formed by a fabricated timber . any form of insulation may be installed , or no insulation at all depending on the application of the wall and / or preferences of the builder . generally , a sufficient quantity of a particular type of insulation is used to provide an insulation r - value ( conventional measure of thermal resistance ) sufficient for the purpose and location of the wall . once a particular course of fabricated timbers have been stacked and attached , any desired utilities have been run , and any tie - down fasteners have been installed and / or extended , then that course of fabricated timbers is typically complete and a next course may be attached . block 550 typically indicates determining if there is at least one additional course to be added to the wall being constructed . if so , method 500 continues again at block 510 . otherwise method 500 continues at block 560 . block 560 typically indicates installing a wall cap at the top of a fabricated timber - based wall . in one example , a wall cap may be fabricated and installed as described in connection with fig3 , elements 332 , 334 , and 336 . installing wall caps may include forming holes so as to enable tie - down fasteners to pass through the wall caps via the holes . further , installing wall caps may include applying a bead ( s ) of caulking and / or glue or the like along the length of a top of the top fabricated timber &# 39 ; s vertical members ( e . g ., 110 and 120 ) prior to installing a wall cap on top of it . such a bead may be applied along the inside and / or outside edge ( s ) of the vertical members , or along any other portion of the vertical members . one such bead may be formed from a caulking or the like that is designed to remain flexible over time , through cycles of hot and cold , and to seal out moisture , bugs , air , and / or other substances and / or objects , and be further designed to maintain a seal given settling , movement , and / or shrinkage of the fabricated timbers and / or wall cap . another such bead may be similarly applied that is formed of glue or construction adhesive or the like . block 570 typically indicates installing tensioner mechanisms to any tie - down fasteners . in one example , such may be installed inside a fabricated timber . in another example , such may be installed on wall caps at the top of a wall . block 580 typically indicates optionally installing chinking in any reveals of the constructed wall , such as reveal 140 of fig1 a that may be provided by fabricated timbers of the wall . such chinking may comprise material that is intended to be functional and / or decorative in nature . conventional chinking materials may be used , and / or other non - conventional chinking materials . for example , mortar , stucco , caulk , grout , and / or the like may be used for chinking . any such materials may be applied using conventional means . in one example , wire mesh may be installed in the reveal area and the chinking material applied over the installed wire mesh . in another example , chinking material may be applied directly to the reveal areas of the stacked fabricated timbers . in another example , electrical wiring may be run along the reveal areas , nail guards installed to protect the electrical wiring , and chinking installed over the nail guard with or without wire mesh . fig6 a is a diagram showing an end view 600 a of an example alternate fabricated timber with a 3 - dimensional view 600 b of the same example alternate fabricated timber illustrated in fig6 b . such a timber according to this example is typically fabricated in a similar manner to that of example fabricated timber of fig1 a and 1 b , with the additional of top horizontal member 190 that may have similar properties , attributes , uses , and characteristics to those of bottom horizontal timber 130 . further , such a timber according to this example can be used in conjunction with fabricated timbers ( e . g ., 100 ). in one example , alternate fabricated timbers ( e . g ., 600 ) may be used for the outside walls of a building while fabricated timbers ( e . g ., 100 ) may be used for inside walls of the same building . the two types of timbers may even both be used in the same wall . other combinations of the two timbers are also acceptable . regarding construction of an alternate fabricated timber ( e . g ., 600 ), top horizontal member 190 may be attached to the tops of vertical members 110 and 120 in a manner similar to that of bottom horizontal member 130 . alternate fabricated timbers ( e . g ., 600 ) may be fabricated to be insulated and fully enclosed either at a fabrication site or on a job site . holes for tie - down fasteners may also be formed either at the fabrication site or on the job site . blocking may be used to enclose the ends of an alternate fabricated timber , and may be built in at approximately two foot or greater intervals along the length of the timber . blocking in both fabricated timbers and alternate fabricated timbers may also include holes configured to provide runs for utilities along the length of the inside of alternate fabricated timbers . an alternate fabricated timber may include conduit ( s ) installed in one or more sets of utility holes in the blocking , the conduit ( s ) typically extending from one end of the timber to the other . such conduits may be used to run utilities through alternate fabricated timbers . blocking in alternate fabricated timbers need not be included on either side of holes formed for tie - down fasteners . further , horizontal members 130 and / or 190 may include channels or grooves along the length of their outer faces ( not shown ), the channels configured to provide a run for electrical wiring or the like . fig7 is a diagram showing an example wall 700 constructed from a plurality of example alternate fabricated timbers ( e . g ., 600 ). like reference numbers refer to like elements within fig7 and between figures . wall 700 is constructed in much the same way as wall 300 , with some variations to account for the use of alternate fabricated timbers ( e . g ., 600 ) versus fabricated timbers ( e . g ., 100 ). one variation may be how one course of alternate fabricated timbers is attached to another course . in one example , strapping 720 is run along adjoining reveals of two stacked courses of alternate fabricated timbers and attached with fasteners 710 at regular intervals , such as approximately every twenty - four inches . strapping 720 may be formed of solid or perforated metal or the like configured for using nails or the like as fasteners 710 . alternatively , strapping 720 may be formed of various sized plates or the like , or of construction tape or the like with adhesive or the like performing the function of fasteners 710 . in another example , individual brackets or the like may be used at intervals along the length of courses . other mechanisms may alternatively and / or additionally be utilized to lock one course to another course when using alternate fabricated timbers . in one example , the tensioner mechanism and related components may be installed on top of the wall top cap . in another example , the tensioner mechanism may be installed inside the top fabricated timber 600 t against its bottom horizontal member . another variation may be how blocking is locked into place in an alternate fabricated timber . in one example , blocking in alternate fabricated timbers may be installed at four - foot or less intervals . fasteners may be installed via the top and bottom horizontal members of an alternate fabricated timber as opposed to via the vertical members . this approach has the advantage of fasteners not being visible on the outside vertical faces of an alternate fabricated timber . another variation may be how a tensioner mechanism and related components are configured . in one example , a plate 733 or the like may be used in conjunction with a tensioner mechanism and a washer 335 and nut 336 . plate 335 is typically configured to distribute forces from any tensioner mechanism ( s ) ( e . g ., 734 ) down the vertical members of alternate fabricated timbers to the foundation . plate 335 may be made of metal or any other material configured to provide the required force distribution . in one example , plate 335 is a steel plate between ⅛ ″ and ½ ″ in thickness that extends substantially across the width of the mating surface of the bottom horizontal member . in another example , plate 335 may alternatively be formed of angle iron or the like , or i - beam or channel or the like . other variations may also include how a bottom course of alternate fabricated timbers is attached to a foundation , how a tie - down fastener is attached to an alternate fabricated timber , etc . further , alternate fabricated timbers ( e . g ., 600 ) may be used in combination with fabricated timbers ( e . g ., fig3 , 100 ). in one example , regular fabricated timbers ( e . g ., fig3 , 100 ) may be used against a foundation as described in connection with fig3 , 100 i , and a top horizontal member may optionally be added . in another example , regular fabricated timbers ( e . g ., fig3 , 100 ) may be used for a top course along with regular wall cap members ( e . g ., fig3 , 332 / 334 ). in another example , a member ( e . g ., 714 ) similar to a horizontal member of a fabricated timber may be disposed atop the foundation ( e . g ., 310 ) and a first alternate fabricated timber be stacked and attached atop the member ( e . g ., 714 ). in one example , such a member ( e . g ., 714 ) may be made of pressure - treated 2 × lumber or the like . such a configuration may provide a reveal at as bottom course that is consistent in depth and height with that resulting from two alternate fabricated timbers stacked one atop the other . solid tall wood timbers tend to be very expensive because old growth trees of sufficient size are scarce . therefore , tall timbers tend to be desirable . fig8 illustrates an example of construction of a tall fabricated timber that has the appearance of an expensive solid tall wood timber . such a tall fabricated timber may be constructed for use as a fabricated timber ( e . g ., 100 ) or as an alternate fabricated timber ( e . g ., 600 ). fig8 illustrates construction of a tall fabricated timber comprising three sections . in one example , section 1 is a fabricated timber ( e . g ., 100 ). sections 2 and 3 are tall fabricated timber sections . section 2 is shown stacked upon and attached ( e . g ., by fasteners 840 on both sides ) to section 1 . arrows 890 indicates stacking section 3 on section 2 . in one example , as illustrated by section 3 , a tall fabricated timber section comprises vertical members 810 and 820 that are typically formed of the same material as vertical members 110 and 120 . the height of vertical members 810 and 820 need not be the same as that of 110 and 120 . in one example , the base member ( e . g ., 830 + 831 ) of each tall fabricated timber section is typically made of two pieces of 2 × lumber attached together as illustrated using any suitable means . alternatively , the base member may be made of a single piece of lumber or other material . typically , the base member extends along the length of the section . such sections may be stacked , compressed , and attached as described elsewhere herein , resulting in a tall fabricated timber . such a tall fabricated timber may be up to the height of a wall it is used to form . fig9 illustrates an example of construction of a single - reveal fabricated timber ( e . g ., 900 i , 900 , and 900 t ) that has the appearance of an expensive solid tall wood timber on one side and a reveal on the other side . either side may be used on the inside or outside of a building . such a single - reveal fabricated timber may be constructed in much the same manner as a fabricated timber ( e . g ., 100 ) and / or an alternate fabricated timber ( e . g ., 600 ). vertical member 920 varies from vertical member 120 in that its height is the same as that of the entire timber . horizontal member 930 varies from horizontal member 130 in that its width is sufficient to provide a desired reveal on one side while the end of the other side abuts the inside bottom face of vertical member 920 such that the bottom face of horizontal member 930 is even with and parallel to the bottom end of vertical member 920 , as illustrated . such single - reveal fabricated timbers may be stacked , compressed , and attached using fasteners ( e . g ., 840 ) as described elsewhere herein . fig1 illustrates an example of construction of a single - reveal alternate fabricated timber ( e . g ., 1000 i , 1000 , and 1000 t ) that has the appearance of an expensive solid tall wood timber on one side and a reveal on the other side . either side may be used on the inside or outside of a building . such a single - reveal alternate fabricated timber may be constructed in much the same manner as a fabricated timber ( e . g ., 100 ) and / or an alternate fabricated timber ( e . g ., 600 ). vertical member 920 varies from vertical member 120 in that its height is the same as that of the entire timber . top and bottom horizontal members 930 vary from horizontal member 130 in that their width is sufficient to provide a desired reveal on one side while the end of the other side abuts the corresponding inside top or bottom face of vertical member 920 such that the corresponding top or bottom face of horizontal member 930 is even with and parallel to the corresponding top or bottom end of vertical member 920 , as illustrated . such single - reveal alte4rnate fabricated timbers may be stacked , compressed , and attached using fasteners ( e . g ., 710 , 720 , and 840 ) as described elsewhere herein . fig1 illustrates front and side views of an example fabricated timber end cap ( e . g ., 1100 ). such end caps may be attached to exposed ends of wall timbers where the height and width of each end cap is typically equal to the height and width of its corresponding timber end . any suitable method of attachment may be used , including fasteners such as nails , glue , and / or any others indicated herein and / or the like . each end cap may be beveled , as illustrated , or otherwise shaped as desired . further , such end caps may be dressed , either prior to or after attachment , so as to match the appearance of their timbers and / or to create the appearance of being integral portions of their timbers .	4
referring to fig1 , an embodiment 10 of a wireless system in accordance with the invention uses a local medium reservation technique to schedule access to a wireless transmission medium . in this manner , the wireless system 10 includes local stations 20 ( stations 20 a and 20 b , as examples ) that may each reserve exclusive access to the wireless transmission medium for a scheduled time slot . during this scheduled time slot , the local station 20 that holds the reservation may communicate several frames without being interrupted by another one of the local stations 20 . as a result of this arrangement , the system 10 supports high bandwidth wireless communications that are well suited for real time data , such as voice and / or video traffic . to accomplish these features , the system 10 is designed to maintain information regarding future traffic over the wireless medium , prioritize real time traffic over non - real time data and schedule access to the shared medium , as described below . more particularly , in some embodiments of the invention , the system 10 may include cells 50 that each includes a group of the local stations 20 . thus , as an example , a cell 50 a may include the three local stations 20 a that are depicted in fig1 , and another cell 50 b may include the three local stations 20 b that are also depicted in fig1 . each cell 50 , in turn , may include an access point ( ap ) 30 that establishes communication between the local stations 20 of the cell 50 and a wired network 40 , such as an ethernet network , for example , or the aps 30 may communicate with each other through the wireless interface . in some embodiments of the invention , the stations 20 and 30 use a contention protocol , such as a carrier sense multiple access / collision avoidance ( csma / ca ) protocol , for purposes of avoiding collisions for contention access to the wireless transmission medium . in some embodiments of the invention , the ieee 802 . 11 wireless local area network ( wlan ) standard may generally govern communication across the wireless medium . for purposes of reserving a time slot ( i . e ., for purposes of reserving bandwidth ) to the wireless medium for real time access , the system 10 uses carrier sense information and properties of the real time traffic ( voice , streaming video , etc .) in its medium reservation policy , as described below . in this manner , in some embodiments of the invention , each cell 50 includes a central authority 42 ( that may be located within the ap 30 of the cell 50 , for example ) that interacts with a particular local station 20 to reserve bandwidth using a technique 60 that is depicted in fig2 . referring to fig2 , more particularly , a local station 20 may request ( block 61 of fig2 ) that a particular bandwidth be reserved for a given traffic type over a defined period of time . this reservation request is received and analyzed ( block 62 ) by the central authority 42 ; and depending upon the underlying network properties , desired traffic characteristics and the policy applicable to the requesting real time station , the central authority 42 determines ( diamond 66 ) whether the central authority 42 will grant or deny the request . based on this determination , the central authority 42 communicates a frame to the requesting station 20 indicating either denial ( block 76 ) or the grant ( block 78 ) of the request . if the request is granted , the central authority 42 calculates ( block 74 ) the duration and the periodicity of the transmissions for the requesting station 20 to meet the throughput and delay requirements of the real time traffic and indicates the reserved time slot in the frame that is transmitted ( block 78 ) to the requesting station . for purposes of tracking the reserved time slots and for purposes of determining which time slots are available , the central authority 42 uses a reservation vector that is described below . in some embodiments of the invention , the system 10 uses the properties of carrier sense functions that determine the state of the wireless transmission medium to ensure that no other local station 20 attempts to transmit during a reserved time slot . for example , in some embodiments of the invention , the system 10 uses the csma / ca protocol , a protocol that uses physical and virtual carrier sense functions are used to determine the state of the wireless medium . when either the physical or the virtual carrier sense functions of a local station 20 that needs to transmit indicate that the wireless transmission medium is busy , transmission is deferred . the virtual carrier sense mechanism in csma / ca takes the form of a network allocation vector ( nav ) that indicates the busy status and the duration of transmission over the wireless medium . the central authority 42 uses this virtual carrier sense mechanism and before each reserved time slot begins ( as indicated by the reservation vector ), it transmits frames that include information to populate the navs ( that are maintained locally by all stations 20 within the cell 50 ) with indication that the wireless transmission medium is busy during the upcoming reserved timeslot . this action causes the virtual carrier sense function , provided by the medium access control ( mac ) layer in each station 20 , to conclude that the wireless transmission medium is busy during the reserved period . therefore , in the scheme described herein , each local station 20 makes the medium access decision locally but the medium reservation control is carried out centrally by the central authority 42 . in some embodiments of the invention , the scheme may be used across multiple cells 50 in the following manner . first , the requesting local station 20 transmits the initial reservation request to the local central authority that , in turn , transits the request across all cells 50 where bandwidth reservation is required . for example , the cells 50 in which this occurs may be all cells 50 that are adjacent to and including the cell 50 of the requesting station 20 . next , the central authorities 42 of these cells 50 reserve the time slots ( if possible ) and update their reservation vectors . reserving the bandwidth across adjacent cells 50 provides a solution to prevent interference from adjoining cells . fig3 depicts a reservation request frame ( rrf ) 100 that is transmitted by a local station 20 to reserve a specified bandwidth over a predefined period of time . one field 102 of the rrf 100 indicates a type of the frame . in this manner , the rrf 100 may be a reservation , cancellation , or refresh frame . a local station 20 transmits a reservation type rrf 100 for purposes of requesting the reservation of bandwidth for a particular time slot . a local station 20 transmits a cancellation type rrf to cancel a previously reserved time slot . a local station 20 transmits a refresh type rrf to renew a reserved time slot . a central authority 42 may also transmit a refresh type rrf after a particular reserved time slot expires to alert the corresponding local station 20 that renewal of the time is required , as further described below . another field 104 of the rrf 100 indicates a type of the traffic to be transmitted during the reserved time slot . for example , the field 104 may indicate whether the traffic to be transmitted during the reserved time slot is voice or streaming video traffic . a field 106 of the rrf 100 indicates a priority of the traffic . another field 108 of the rrf 100 indicates the required throughput for the given type of traffic . use of the field 108 , in some embodiments of the invention , is optional and may be used only if the traffic type is unknown . the rrf 100 may also include a field 110 to indicate the periodicity , the maximum time interval between successive transmissions . in some embodiments , the field 110 is optional and may be used only if the traffic type is unknown . upon reception of an rrf 100 , the central authority 42 examines the parameters indicated by the rrf 100 and the central authority &# 39 ; s reservation vector to determine if a time slot may be reserved . an exemplary reservation vector 150 is depicted in fig4 . as shown , the reservation vector 150 indicates a bandwidth reservation window 151 that includes time slots 160 that are reserved for the local stations 20 . for example , a particular local station 20 may have time slots 160 in that are denoted by “ sta 1 ”, and another station 20 may have time slots 160 ( in the reservation vector 150 ) that are denoted by “ sta 2 .” as shown , in some embodiments , any two adjacent reserved time slots 160 are separated from each other by a contention time slot 162 , a time slot in which the local stations 20 that do not have reserved periods may transmit using the csma / ca contention protocol . once the central authority 42 receives an rrf that requests a reservation , the central authority 42 ascertains if sufficient resources are available based on the throughput offered by the underlying network , the latency , carrier sense information , the amount of requested bandwidth , and the policy that is applicable to the requesting local station 20 . if resources are available , then the central authority 42 calculates the duration ( called “ ι ”) of each transmission according to the following formula : t = ρ · r t a t + λ , equation ⁢ ⁢ 1 where “ r t ” is the required throughput , “ a t ” is the throughput offered by the underlying network , “ ρ ” is the periodicity and “ λ ” is the network latency . once the central authority 42 fulfills the request , the central authority 42 transmits an acknowledgment frame to the requesting station 20 , a frame that indicates the time at which the reserved time slot begins . the central authority 42 includes a scheduler that performs a technique 180 that is depicted in fig5 . in the technique 180 , the scheduler “ wakes ” up ( block 182 ) before each scheduled transmission period and transmits ( block 184 ) a frame that populates the navs of the local stations 20 that are not going to transmit during the reserved time slot with the duration of the next reserved transmission . this event causes the virtual carrier sense mechanism that is provided by the mac layer of each local station 20 to conclude that the medium is busy and defer transmission . therefore , the medium access decision is taken by the virtual carrier sense mechanism local to each station 20 , and the reservation control information is sent by the central authority 42 . the central authority 42 grants a reserved time slot only for a determined period of time , and the duration of this time may be negotiated with the requesting station 20 when the requesting station 20 transmits a reservation request ( in the form of an rrf ) for the first time . basing the duration of the time slot on the available resources ( as described above ), the central authority 42 responds to the request with an indication of the actual period of time for which the reservation is granted . at the expiration of a reservation period , the central authority 42 sends out a refresh notice ( via an rrf frame 100 ) to the appropriate local station 20 . if the local station 20 does not respond with a refresh request ( via an rrf frame 100 ), the central authority 42 frees up any resources that are allocated to the local station 20 and removes the associated time slot from its reservation vector . reservation periods may be cancelled by local stations 20 ( via an rrf frame 100 ), and upon reception of a reservation cancellation frame from a particular local station 20 , the central authority frees up the time slot 160 ( and thus , the bandwidth ) that is allocated to the station 20 and adds the additional time to the contention free time slots 162 . in some embodiments , the central authority 42 may free up the time slots 160 that are allocated to a particular local station 20 if that local station 20 does not transmit during one of its allocated time slots 160 . the scheme described above has the added advantage of working well even when adjacent cells 50 share the same frequency . in this manner , the frame transmitted by the central authority 42 to populate the navs would also be received by stations in the adjacent cell 50 , which would lead to them defer transmissions during the reserved period . thus , interference from neighboring cells 50 is minimized in the above - described scheme . referring to fig6 , in some embodiments of the invention , the central authority 42 may include a control unit 202 ( a computer , a computer unit , a microprocessor or any other type of processor , as examples ) that may execute routines in the form of a program 200 to perform the scheduling and reservation techniques that are described herein . the central authority 42 may include a storage unit 204 ( a hard disk drive or a cd - rom drive , as examples ) that may store a copy of the program 200 . other arrangements are possible . other embodiments are within the scope of the following claims . for example , in cases where multiple access points are present within the same cell 50 , in some embodiments of the invention , the central authority 42 may dynamically choose to route real time traffic through the access point that has the least existing traffic . as another example , in cases where carrier frequencies overlap in the same cell 50 , in some embodiments of the invention , the central authority 42 may choose to transmit real time traffic using the carrier frequency that best meets a predefined criteria , such as the carrier frequency in which previous communications had the least error rate or the carrier frequency in which previsous communications had the shortest latencies , as examples . while the invention has been disclosed with respect to a limited number of embodiments , those skilled in the art , having the benefit of this disclosure , will appreciate numerous modifications and variations therefrom . it is intended that the appended claims cover all such modifications and variations as fall within the true spirit and scope of the invention .	7
referring to fig1 , the workpiece transfer system 10 includes a bar 12 that moves a workpiece 20 between workstations ( not shown ). an adaptor 14 is attached to the bar 12 and supports the tools 18 . the tools 18 extend from removable rails 16 attached to the adaptor 14 . the tools 18 illustrated are pneumatically actuated suction cups . however , other tools as are known would also benefit from the disclosures of this invention , for example mechanical grippers and part present sensing devices . the rail 16 is part of a rail assembly . there are four rail assemblies 42 , 44 , 46 and 48 illustrated . the tools 18 are mounted to arms 22 that are in turn mounted to the rail 16 of each rail assembly 42 , 44 , 46 and 48 . the position of the tools 18 along the rail 16 is infinitely adjustable such that the configuration and placement of the tools 18 can be tailored to the requirements of a specific application and workpiece 20 . each of the rail assemblies 42 , 44 , 46 and 48 include a mount plug 25 that is attachable to selectively releasable mount connector 24 attached to the adaptor 14 . the mount plug 25 is affixed to a first end of the rail 16 for each of the rail assemblies 42 , 44 , 46 and 48 . the mount plug 25 interfaces with the mount connector 24 to communicate pressurized air and provide an electrical connection for any electrical devices mounted to the rail 16 . the mount connector 24 includes a locking device 27 movable between a released position where the rail 16 may be removed and a secured position where the rail 16 is rigidly held into the mount connector 24 , and the desired electrical and pneumatic connections are completed . the example rail assembly 42 includes a sensor 38 for detecting the presence of the workpiece 20 . the sensor 38 is electrically attached through the interface between the mount plug 25 and the mount connector 24 . the mount connector 24 is in turn in communication with a source of electrical energy and pressurized air . further , the mount connector 24 is adaptable for providing communication of control signals to the tools 18 mounted to the rail 16 . the mount connector 24 also provides support of an end of the rail 16 . the second end 28 of the rail 16 is supported by a lug 32 that fits within a lug mount 30 . the lug 32 on the rail 16 is first placed within the lug mount 30 and slid axially into full engagement with the mount connector 24 . the lug mount 30 receives the lug 32 within a slot 35 that includes a vertical portion 37 and horizontal portion 39 . the lug 32 drops within the vertical portion 37 of the slot 35 and is slid axially within the horizontal portion 39 of the slot to facilitate axial engagement and securement of the mount plug 25 within the mount connector 24 . although a mount connector 24 and mount plug 25 are illustrated , it is within the contemplation of this invention to utilize other mounting devices that are known in the art . the rail assemblies 42 , 44 , 46 and 48 are installed to the adaptor 14 in a specific location . each of the rail assemblies 42 , 44 , 46 and 48 are adapted to fit only one location to assure a desired orientation of the rail assemblies 42 , 44 , 46 and 48 to comply with application specific requirements . each of the rail assemblies 42 , 44 , 46 and 48 are identified by a color code . the color of the lug 32 corresponds to a color on the lug mount 30 to provide a determination of the correct position for mounting of the rail assembly . the color code in the illustrated example is green for the rail assembly 42 and is indicated schematically by shading 17 b on the the rail assembly 42 and shading 17 a on the lug mount 30 . the rail assembly 46 includes a gold color code schematically indicated at 19 a on the rail 16 and a matching gold color indicated at 19 b on the lug mount 30 . the rail assembly 44 includes a silver color code ( not shown ) and the rail assembly 46 includes a black color code ( not shown ). the color - codes 17 a and 19 a disposed on the rail 16 of each rail assembly 42 , 46 comprise a colored tape . the color - codes 17 b and 19 b on the lug mounts 30 are provided by a desired plating color . as appreciated , other colors and method of adhering that color to the lug mount and the rail may be utilized to identify each position on the adaptor 14 with the corresponding one of the rail assemblies 42 , 44 , 46 and 48 . the different color codes provide for easy identification of the proper location for the rail assembly . referring to fig2 , the rail assembly 42 is illustrated removed from the rail adaptor 14 . the rail assembly 42 , like the other rail assemblies 44 , 46 and 48 includes a length 50 between the lug 32 and a portion of the mount plug 25 . the length 50 for each of the rail assemblies is unique such that one rail assembly cannot be assembled into the place of another rail assembly . in the example illustrated in fig2 , the rail assembly 46 includes a length 54 that is different than the length 50 such that the rail assembly 46 cannot be assembled in place of the rail assembly 42 . the length 50 between the lug 32 and the end of the mount plug 25 corresponds to a length 52 between the mount connector 24 and the lug mount 30 . the length 52 is measured from a stop of the mount connector 24 and a position within the horizontal portion 39 of the slot 35 within the lug mount 30 . the length 50 between the lug 32 and the end of the mount plug 25 is a dimension that is fabricated within desired tolerances to provide the desired fit once mounted . as appreciated , some prior art tool mounting devices include multiple critical dimensions that must be closely controlled to provide the desired fit , or event to allow assembly . the instant tool mounting system includes only a single closely held dimension , thereby simplifying assembly , and fabrication . the rail assembly 42 is easily removable by unlocking the mount plug 25 from the mount connector 24 and moving the entire rail axially away from the mount plug 25 until the lug 32 is free to move vertically within the slot 35 of the lug mount 30 . another rail assembly including tooling for a differently shaped and configured workpiece can then be installed to provide a relatively quick and easy tooling change over . in operation , several sets of rail assemblies will be provided that correspond to various and differently configured workpieces . change over is conducted by removing one set of color - coded rail assemblies and installing another set in the proper color coded locations . rail assemblies can only be properly installed into corresponding locations due to the different lengths 50 and 54 between the mount connector 24 and the lug mount 30 . referring to fig3 , the lug mount 30 is shown without the rail and adaptor for clarity . the lug mount 30 includes the slot 35 having the vertical portion 37 and the horizontal portion 39 . the drop down feature provided by the lug 32 being received in the slot 35 facilitates quick assembly of a rail assembly . the lug 32 includes a bushing 33 that supports the tool and prevents twisting during installation . the drop down feature thereby prevents twisting of the rail assembly during assembly , thereby substantially eliminating the need for an assembler to support the rail assembly during the entire assembly process . referring to fig4 , the lug mount 30 is shown schematically that correspond to mounting arrangements for the rail assembly 42 and the rail assembly 46 . the slot 35 includes a width 58 for the lug 32 . the lug 32 includes the bushing 33 supported on a shaft 31 . the shaft 31 includes a diameter 60 that corresponds with the width 58 that provides for assembly of the lug 32 within the slot 35 . the width 58 is tailored to each of the rail assemblies 42 , 44 , 46 and 48 such that each of the rail assemblies 42 , 44 , 46 and 48 includes a tailored width 58 unique to that particular rail assembly . accordingly , the rail assembly 46 is partially shown with the lug 32 having a shaft 31 of a diameter 64 different than the diameter 60 for the rail assembly 42 . the lug mount 30 for the rail assembly 46 includes a width 62 of the slot 35 ′ that prevents another rail assembly , such as for example the rail assembly 42 from being installed within the lug mount 30 instead of the rail assembly 46 . accordingly , the different diameters for each shaft 31 of each of the rail assemblies 42 , 44 , 46 and 48 substantially prevent assembly of a rail assembly in a non - desired orientation . referring to fig5 , a cross - section of the transfer system 10 is shown with the adaptor 14 attached to the bar 12 . as appreciated , the transfer system 10 operates within a space - restricted environment . in some applications , it is desired to limit or eliminate mounting of devices or objects to the top of the bar 12 . such applications may not allow the mounting of electrical wire harnesses and airlines to the top surface of the bar 12 . in such applications , the instant adaptor 14 provides the necessary mounting and communication of air and electric to the tooling without extending substantially beyond the top surface of the bar 12 . the addition of the adaptor 14 adds only the minimal thickness of the adaptor 14 to the overall height of the bar 12 . accordingly , the inventive workpiece transfer system 10 includes several features that assure proper configuration of the several rail assemblies 42 , 44 , 46 and 48 that expedite and facilitate quick tool changeover . different lengths between mounting points for each rail assembly and tailored diameters of shafts for each lug accompanied by color - coded parts provides for fail safe and efficient tool change over . further , the drop down mounting provided by the lug and lug mount tool mount configuration eases mounting by eliminating awkward and difficult maneuvering of the rail assemblies during the mounting process . although a preferred embodiment of this invention has been disclosed , a worker of ordinary skill in this art would recognize that certain modifications would come within the scope of this invention . for that reason , the following claims should be studied to determine the true scope and content of this invention .	8
the distributor of this invention can be used in conjunction with any type of particle bed . typically , the particle bed and inlet distributor will be located inside a vessel for a catalytic reaction or an adsorption process . this invention finds greatest advantage when used with a vessel having a downward flow of fluid from an inlet nozzle through an unconfined bed of particles . the invention can also be used with confined particle beds . in confined particle beds , large scale shifting of the upstream bed surface is not a concern due to restraint by a screen or other confining device but plugging of the bed surface can still cause excessive pressure drop and poor utilization of the particle bed . this invention is more fully explained in the context of a typical downflow vessel arrangement as shown in fig1 . fluid entering the distributor of this invention may be gaseous phase , liquid phase , or a combination of the two . greatest advantage is obtained when the fluid stream entering through the inlet distributors is in gas phase . the remainder of this description refers to the fluid as a gas . this reference is not meant to limit the invention to gas phase flow . referring again to fig1 an upper pipe 10 delivers a gas phase fluid to a vessel 12 through an inlet nozzle 14 which is connected to pipe 10 through a straight conduit 16 and an elbow 18 . all of the gas flow that enters vessel 12 is intercepted first by distributor 20 . distributor 20 has an inlet plate 22 flanged to the top of inlet nozzle 14 . plate 22 secures distributor 20 to vessel 12 and provides a seal between nozzle 14 and inlet plate 22 that prevents fluid from entering vessel 12 without first passing through distributor 20 . other well - known means of attaching distributor 20 to vessel 12 can be used . nevertheless , whatever method of attachment is used , it is important that the method prevent bypassing of fluid around distributor 20 and into the vessel 12 . distributor 20 disperses the gas over the cross - section of vessel 12 . the dispersed gas enters a particle bed 24 having an upper surface 25 . bed 24 is composed of solid particles which can be in the form of pills , spheres , cylinders , or other extruded shapes . the actual properties of the particles will depend upon the process which is carried out in the containment vessel . generally , particles will consist of an adsorbent or a catalyst . as a further means of preventing bed disturbances , a layer of support material , usually comprising ceramic balls , may be added and comprise the upper surface of the particle bed . bed surface 25 will in most cases simply consist of particles that have been leveled at the time of loading . as gas passes across upper surface 25 , it proceeds down through the remainder of bed 24 . if the top surface of the bed remains level and open , a complete redistribution of the gas is usually effected such that it will pass uniformly through the remainder of the bed . therefore , it is not essential that distributor 20 provide a completely uniform distribution of gas across the bed surface 25 . in the past , the distributor 20 was to provide a fluid , or in this case gas dispersion , that has enough uniformity to eliminate any concentrated jets of fluid having sufficient velocity to disrupt surface 25 . after a predetermined contact time , gas leaves the catalyst bed 24 by passing through a porous support member 26 . member 26 can be screen or any other rigid layer of porous material having sufficient strength to support the weight and pressure loading of catalyst bed 24 . exiting gases pass through an outlet screen 28 that collects any fine particles that have passed out of a catalyst bed and through support member 26 . from screen 28 , exiting gases leave the vessel 12 through an outlet nozzle 30 which is connected to a lower pipe 32 . fig1 also shows one of the prior art methods for collecting debris that would gather at the top of a downflow reactor . debris collectors , or baskets 34 , are shown having an opening 36 for admitting gas into the collector and downwardly extended sidewalls 38 for distributing gas from the interior volume 40 of the basket into the adjacent portions of the bed . the bottom of the basket has end closure 42 to prevent bed particles from moving upward into the interior 40 of the basket . with the distributor of this invention , baskets 34 are no longer necessary and would not be present at the top of the bed . fig2 illustrates one form of the apparatus and method of this invention . a gas stream containing solid debris enters the top of vessel 12 &# 39 ; through a conduit 16 &# 39 ;. conduit 16 &# 39 ; directs the gas downwardly into a fluid distributor 44 . fluid distributor 44 has perforated sidewalls 46 that are located between the bottom of the inlet nozzle 14 &# 39 ; and a baffle 48 located inside the distributor 44 and arranged in the form of a series of diagonal vanes 49 . as gas flows downwardly in the distributor , the momentum of the solid particles carries them through baffle 48 while the lighter gases are diverted radially outward through the sidewall 46 . the openings in the perforated portion of the distributor sidewall need not be smaller than the debris that is sought to be trapped within the inlet distributor . the primary mechanism for the removal of the particles in this arrangement is the downwardly directed momentum of the particles which carries the particles out of the gas flow and past the baffle 44 . the sidewall 50 and bottom 52 of the distributor form a collection zone 53 below the baffle 48 . the sidewalls 50 and bottom 52 are at least closed to any flow of the solid particles out of the bottom of the distributor and are typically completely closed to fluid flow . when the bottoms and sidewalls 50 and 52 are completely sealed , the volume of the distributor around and below the baffles has no net fluid flow and is essentially dead space . as the particles enter the space below the baffle 48 , they come to rest at the bottom of the distributor . baffles 48 prevent any eddy current from the redirection of the fluid above the baffles from disturbing the particles below the baffle and reentraining them with the outgoing flow of gas from the distributor . it may be desirable in some cases to have some fluid flow through sidewalls 50 and bottom 52 in the collection zone of the distributor . in such cases , the bottoms and sidewalls can be composed of very fine screen that will not permit solid particles to escape from the collection zone . such an arrangement may be advantageous where the debris is very fine and some small fluid flow through the collection zone would serve to prevent any migration of fine dust debris back into the space of the distributor above baffle 48 . however , such an arrangement is not desired where the debris comprises heavy viscous liquids that may eventually seep through any permeable surface in sidewall 50 or bottom 52 . however , any fluid flow that passes through the distributor below the baffle 48 must be kept low in order to achieve the objectives of this invention . the directing of particles into the collection zone of the distributor may be further improved by the arrangement of the invention shown in fig3 . in this arrangement gases enter the contacting vessel 12 &# 34 ; through a conduit 16 &# 34 ;. conduit 16 &# 34 ; discharges the particles into an inlet distributor 44 &# 39 ; that has a perforated portion 46 &# 39 ; of a sidewall through which the gases exit the inlet distributor . particles and debris collect below baffle 48 &# 39 ; in a collection zone 53 &# 39 ;. the outlet end of conduit 16 &# 34 ; extends downwardly into the inlet distributor past the lower extent of the perforated portion of the sidewall 46 &# 39 ;. the extension of conduit 16 &# 34 ; prevents the deflection or migration of any of solid particles to the outside of the distributor in the region of the perforated sidewall . in the arrangement of fig3 the flow is thereby confined to direct more of the particles on to the baffles 48 &# 39 ;. the arrangement of fig3 is most suitable for lower flow velocities where the gas flow through conduit 16 &# 39 ; will not create large cross - currents that could reentrain particles into the gas flow exiting through perforated portion 46 &# 39 ;. a variety of different arrangements can be used for the baffle in the bottom of the distributor . the sloped vanes of fig2 and 3 are shown in fig4 where parallel vanes 49 are spaced transversely across the cross - section of the inlet distributor . the plates 49 are spaced apart and extend in a parallel direction and cover essentially the entire transverse cross - section of the inlet distributor to shield the collection zone from direct gas flow . those skilled in the art are aware of a variety of suitable plate configurations such as conical or annular plate sections .	1
before the present composition for wound healing is disclosed and described , it is to be understood that this invention is not limited to the particular configurations , process steps , and materials disclosed herein as such configurations , process steps , and materials may vary somewhat . it is also to be understood that the terminology employed herein is used for the purpose of describing particular embodiments only and is not intended to be limiting since the scope of the present invention will be limited only by the appended claims and equivalents thereof . as described above , the present invention is directed to a composition for stimulating cell growth and the healing of wounds by administering a pharmacologically effective amount of grown factors directly to the affected tissue . the composition may be used to treat any type of non - healing wound whereby fibroblast activity is reduced or ineffective . such wounds include diabetic non - healing wounds , burns , osteomyelitis , trauma wounds , subcutaneous trauma and various forms of dermatitis . the composition may also be employed to stimulate hair growth on the scalp and other body areas . the growth factors of the present invention have been identified in hen &# 39 ; s egg whites . ovalbumin is the major constituent of egg whites from the hen comprising about 75 % by weight of the egg white . the molecular weight of ovalbumin is approximately 4 , 500 , and ovalbumin is produced under hormonal control by the bird oviduct . it may be isolated and crystallized readily from the filtrate of an acidified mixture of egg white and an equal volume of saturated ammonium sulfate . sorensen et al ., c . r . trav . lab . carlsberg 12 , 12 ( 1917 ). alternative methods of isolation of ovalbumin are disclosed by kekwick et al ., biochem journal 30 : 227 ( 1930 ). ovalbumin can also be separated by electrophoresis and chromatography from about 10 other minor components found in egg whites including avidin ( qv ), lysozyme ( qv ), conalbumin ( qv ), and ovomucoid . the structure of ovalbumin is that of a complex protein consisting of a single polypeptide chain of about 460 residues ( about half of which are hydrophobic ), a maximum of 2 phosphate residues per mole , and a oligosaccharide side chain composed of only mannose and glucosamine residues . see narita , j . biochem . 52 : 367 ( 1962 ); thompson et al ., aust . j . biol . science 24 : 525 ( 1971 ). ovalbumin is soluble in electrolyte free water and combines with salts , acids and bases . denaturation can be induced by heating to 56 ° c ., by vigorous shaking , by electric current and by various chemicals such as acids , ammonium salts , heavy metal salts and alcohols . such methods produce complete and irreversible denaturation . the isoelectric point of ovalbumin is 4 . 63 . see merck index ( 12 th ed . 1996 ). in accordance with the compositions and method of the present invention , ovalbumin may be administered in the form of a pharmaceutical composition additionally comprising pharmaceutically acceptable carrier . one skilled in the art will appreciate that suitable methods of administering the ovalbumin compositions to an animal , such as a mammal , are available and , although more than one method can be used to administer a particular composition , a particular method and dosage can provide a more immediate and more effective reaction than others . pharmaceutically acceptable carriers are also well known to those skilled in the art . the choice of carrier will be determined , in part , both by the particular composition and by the particular method used to administer the composition . accordingly , there is a wide variety of suitable formulations of the pharmaceutical compositions of the present invention . the present invention is preferable in the form of a topical dosage form such as creams , ointments , lotions , gels or powders . the present invention may be formulated as necessary with additives used commonly in the pharmaceutical sciences , such as surfactants , oils and fats , polyhydric alcohols , lower alcohols , thickening agents , uv absorbents , light scattering agents , preservatives , antioxidants , antibiotics , chelating agents , ph regulators , flavoring agents , pigments and water . examples of surfactants include polyoxyethylene ( hereinafter abbreviated as poe -) branched alkyl ethers such as poe - octyldodecyl alcohol and poe - 2 - decyltetradecyl alcohol , poe - alkyl ethers such as poe - oleyl alcohol ether and poe - cetyl alcohol ether , sorbitan esters such as sorbitan monooleate , sorbitan monoisostearate and sorbitan monolaurate , poe - sorbitan esters such as poe - sorbitan monooleate , poe - sorbitan monoisostearate and poe - sorbitan monolaurate , fatty acid esters of glycerol such as glyceryl monooleate , glyceryl monostearate and glyceryl monomyristate , poe - fatty acid esters of glycerol such as poe - glyceryl monooleate , poe - glyceryl monostearate and poe - glyceryl monomyristate , poe - dihydrocholesterol ester , poe - hardened castor oil , poe - hardened castor oil fatty acid esters such as poe - hardened castor oil isostearate , poe - alkylaryl ethers such as poe - octylphenol ether , glycerol esters such as glycerol monoisostearate and glycerol monomyristate , poe - glycerol ethers such as poe - glycerol monoisostearate and poe - glycerol monomyristate , polyglycerol fatty acid esters such as diglyceryl monostearate , decaglyceryl decastearate , decaglyceryl decaisostearate and diglyceryl diisostearte and other nonionic surfactants ; potassium salts , sodium salts , diethanolamine salts , triethanolamine salts , amino acid salts and other salts of higher fatty acids such as myristic acid , stearic acid , palmitic acid , behenic acid , isostearic acid and oleic acid , the above alkali salts of ether carboxylic acids , salts of n - acylamino acids , n - acylsalconates , higher alkylsulfonates and other anionic surfactants ; alkylamine salts , polyamine , aminoalcohol fatty acids , organic silicone resin , alkyl quaternary ammonium salts and other cationic surfactants ; and lecithin , betaine derivatives and other amphoteric surfactants . examples of oils and fats include vegetable oils and fats such as castor - oil , olive oil , cacao oil , camellia oil , coconut oil , wood wax , jojoba oil , grape seed oil and avocado oil ; animal oils and fats such as mink oil and egg yolk oil ; waxes such as beeswax , whale wax , lanolin , carnauba wax and candelilla wax ; hydrocarbons such as liquid paraffin , squalene , microcrystalline wax , ceresine wax ; paraffin wax and vaseline ; natural or synthetic fatty acids such as lauric acid , myristic acid , stearic acid , oleic acid , isostearic acid and behenic acid ; natural or higher alcohols such as cetanol , stearyl alcohol , hexyldecanol , octyldecanol and lauryl alcohol ; and esters such as isopropyl myristate , isopropyl palmitate , octyldodecyl myristate , octyldodecyl oleate and cholesterol oleate . examples of polyhydric alcohols include ethylene glycol , polyethylene glycol , propylene glycol , 1 , 3 - butyrene glycol , 1 , 4 - butyrene glycol , diprophylene glycol , glycerol , diglycerol , triglycerol , tetraglycerol and other polyglycerols , glucose , maltose , maltitose , sucrose , fructose , xylitose , sorbitol , maltotriose , threitol and erythritol . examples of thickening agents include naturally - occurring high molecular substances such as sodium alginate , xanthene gum , aluminum silicate , quince seed extract , gum tragacanth , starch , collagen and sodium hyaluronate ; semi - synthetic high molecular substances such as methyl cellulose , hydroxyethyl cellulose , carboxymethyl cellulose , soluble starch and cationized cellulose ; and synthetic high molecular substances such as carboxyvinyl polymer and polyvinyl alcohol . examples of uv absorbents include p - amnobenzoic acid , 2 - ethoxyethyl p - methoxycinnamate , isopropyl p - methoxycinnamate , butylmethoxybenzoylmethane , glyceryl - mono - 2 - ethylhexanoyl - di - p - methoxybenzophenone , digalloyl trileate , 2 , 2 ′- dihydroxy - 4 - methoxybenzophenone , ethyl - 4 - bishydroxypropylaminobenzoate , 2 - ethylhexyl - 2 - cyano - 3 , 3 ′- diphenyl acrylate , ethylhexyl p - methoxycinnamate , 2 - ethylhexyl salicylate , glyceryl p - aminobenzoate , homomethyl salicylate , methyl o - aminobenzoate , 2 - hydroxy - 4 - methoxybenzophenone , amyl p - dimethylaminobenzoate , 2 - phenylbenzoimidazole - 5 - sulfonic acid and 2 - hydroxy - 4 - methoxybenzophenone - 5 - sulfonic acid . examples of preservatives include benzoates , salicylates , sorbates , dehydroacetates , p - oxybenzoates , 2 , 4 , 4 ′- trichloro - 2 ′- hydroxydiphenyl ether , 3 , 4 , 4 ′- trichlorocarbanilide , benzalkonium chloride , hinokitiol , resorcinol and ethanol . examples of antioxidants include tocopherol , ascorbic acid , butylhydroxyanisole , dibutylhydroxytoluene , nordihydroguaiaretic acid and propyl gallate . examples of antibiotics include penicillin , neomycin , cephalothin , potassium permanganate , selenium sulfide , erythromycin , bacitracin , tethacyclin , chloramphenicol , vancomycin , nitrofurantoin , acrisorcin , chlorodontoin , and flucytosine . some of these additives function to enhance the efficacy of the composition by increasing the stability or percutaneous absorbability of the essential components of the present invention . also , any dosage form is acceptable , whether in solution , emulsion , powder dispersion , or others . applicability is wide , including fundamental dosage forms such as lotions , emulsions , creams and gels . the composition of the present invention is preferably formulated according to formula 1 : the method for processing and pasteurizing hen egg whites is well known in the art and generally involves reverse osmosis , heating , and drying steps resulting in solid egg whites ready for compounding . in addition to those stated above , suitable vehicles , carriers and adjuvants include water , vaseline , petrolatum , mineral oil , vegetable oil , animal oil , organic and inorganic waxes , polymers such as xanthanes , gelatin , cellulose , collagen , starch , kaolin , carregeenan , gum arabic , synthetic polymers , alcohols , polyols , and the like . the carrier can also include sustained release carrier such as lypizomes , microsponges , microspheres , or microcapsules , aqueous base ointments , water in oil or oil in water emulsions , gels or the like . the dose administered to an animal , particularly a human , in the context of the present invention should be sufficient to effect a therapeutic response over a reasonable time frame . the dose will be determined by the strength of the particular compositions employed and the condition of the person . the size of the dose and the frequency of application also will be determined by the existence , nature , and extent of any adverse side effects that may accompany the administration of a particular composition . the composition of the present invention may be employed to treat diabetic ulcers , healing resistant wounds , bed sores , burns , osteomyelitis , trauma wounds , subcutaneous trauma and various forms of dermatitis . the following examples illustrate the inventive compositions and methods , but should not be regarded as limiting the invention in any manner . additional studies are in progress as of the filing date of this application . in march 1998 a female patient who underwent laminectomy and fusion of t3 and t4 began applying the inventive composition to the surgical wound . this patient experienced no scaring from the surgical wounds and continued to be without scars 10 months post surgery . this patient had a previous history of radical surgery in may 1960 for removal of a right breast tumor . the wound from that surgery healed in approximately one month , but left a large scar . eighteen months after the may 1960 surgery she had major abdominal surgery , and in 1985 had reconstructive of the right and left breast , but with both surgeries experienced significant scaring . thus , with the recent surgery , the inventive composition prevented scaring . the wound healing characteristics of the inventive composition was demonstrated on sprague - dawley rats using a cream according to formula 1 applied to a wound once daily for five days per week . the percentage of wound acceleration in days and in size was compared to control . the percent of wound acceleration in days was determined to be 5 . 19 , and the percent of acceleration in size was determined to be 22 . 07 . note : percentage wound acceleration in days =( 1 − td / cd )× 100 %, where td and cd are the days required for 80 % wound healing in the treatment and control animals , respectively . percent wound acceleration in size =( 1 − ta / ca )× 100 %, where ta and ca are the areas of the wounds in the treatment in control animals , when 80 % wound healing is reached on the former . a male patient routinely plagued by muscle and joint soreness and stiffness related to sports activities on the morning following such activities , applied the inventive composition to the affected areas and found that he experienced no joint soreness the mornings following the sports activities . patient number 964885 has been applying the inventive compositions to a diabetic ulcer on the left foot and has experienced a shrinkage of the wound . a female applied the inventive composition in a cream form to a third degree burn on her left inner forearm . after daily application of the cream to the affected area , the blister reabsorbed readily , and the area healed within seven days with no residual scar tissue . an 88 - year - old patient sustained a fall resulting in several facial abrasions and a 1 . 5 inch laceration over the right eyebrow . with the use of the inventive cream to the affected area , these lacerations healed in about 72 hours leaving no scar tissue . a male who has had diabetes for more than 30 years sustained various skin tears and small ulcers on his upper and lower extremities . daily application of the inventive composition in a cream form has kept the affected areas clean and painfree and healing took place in a relatively short time frame . a wound on a dog &# 39 ; s hind leg was so extensive that the pad of the paw was almost detached . the inventive composition cream was applied and the wound bandaged . a few days later , the veterinarian noticed remarkable healing in that the wound was clean and dry with a good granulation bed , and there was the beginning of granulation across the wound . the extent of the healing was so great that the dog was able to go home with no bandage on its paw . similarly , a filly who had experienced a cut foreleg to the cannon bone was administered the inventive cream and the wound was wrapped . two days later , upon removal of the bandage and checking of the wound , it had healed nicely across with a base of granulation over the periosteum and showed a good , clean , dry wound bed with moist , supple edges . several patients have used the inventive composition for arthritis , foot calluses , dry skin , back pain , bruises , allergies ( including latex allergies ), and inflammation . all such patients reported symptomatic relief using the inventive composition . the composition of the invention ( formula 1 ) was tested using antibodies directed against bovine and other mammalan derived growth factors . in particular , the antibodies used were targeted toward pdgf , fgf a , fgf b , tgfβ , tgfα , and egf . the following antibodies were used for detection of the growth factors . unless noted otherwise the antibodies were purchased from research diagnostics inc ., flanders , n . j . antibodies specificity catalog number identification according to label rdi - pdgfababg goat anti - pdgf recognizes pdgf - aa , - ab , - bb chains of human , primate , bovine and porcine . rdi - bfgfaabm mouse anti - fgf recognizes bovine acidic acidic fgf , human acidic fgf and human basic fgf . rdi - brgfbabm2 mouse anti - bovine recognizes bovine , rat , b . mouse and human fgf - fgf basic rdi - tgfbabmx mouse anti - human recognizes human , mouse tgf - b and bovine tgfb1 and b2 , also xenopus tgfb3 . rdi - tgfaabmb mouse anti - human recognizes mouse , rat and tgf - a human tcg - a rdi - msegfcabg goat anti mouse egf recognized mouse and c - term human egf at carboxy terminus donkey anti - goat igg ( h & amp ; l ) linked to biotin sp used for egf and pdgf antibodies . horse anti - mouse ( igg ( h & amp ; l ) linked to biotin used for all other antibodies . protein concentration was determined by the bca assay ( pierce ) according to manufacture &# 39 ; s instructions . ppt mg54 - 2 — 21 mg / ml 1 mg54 - 2 jul . 24 , 1997 115 mg / ml 2 mg54 - 3 sep . 8 , 1997 55 mg / ml for control samples crude rat brain homogenates were generated and run in adjacent lanes to samples of the inventive composition . separation of proteins was carried out in modified form from the procedures of laemmli ( nature 227 : 680 - 685 ( 1970 )). samples and controls were electrophoresed on a 15 % sds - page gel . 40 μg of sample or - control was loaded onto each lane . samples to test for pdgf and tgfb were run under non - reducing conditions as specified by the supplier of the primary antibody . all other samples and controls were run under reducing conditions . the samples were electrophoresed for 45 minutes at 200 v . the gel was placed on a pvdf membrane and electrophorectically transferred for one hour at 25 - 30 amps . the membrane was blocked for one hour in pbs containing 5 % nonfat dry milk . the primary antibodies were diluted in preparation for incubation with the membrane . unless otherwise noted the antibodies were diluted in pbs . the concentration of the antibodies used was as follows : goat anti - human pdgf - ab 10 ug / ml mouse anti - human tgfb 1 ug / ml in pbs with 1 mg / ml bsa mouse anti - bovine basic fgf1 ug / ml mouse anti - bovine acidic fgf 1 ug / ml in pbs with 5 mg / ml bsa mouse anti - human tgf a 10 ug / ml mouse anti - goat egf 10 ug / ml lanes were cut from the membrane and incubated overnight at 4 ° c . with the primary antibody of interest . the membrane strips were washed for one hour in pbs - tween ( 0 . 05 % tween 20 ) and incubated for two hours with the secondary antibody of choice diluted in pbs . for landes incubated with goat derived primary antibodies , biotin linked donkey anti - goat igg at 1 : 10 , 000 dilution was used as secondary antibody . for lanes incubated with mouse derived primary antibody , biotin linked horse anti - mouse igg at 7 . 5 μg / ml diluted in pbs ( 1 : 200 ) with 1 % normal horse serum was used as secondary antibody . the membrane strips were washed for one our in pbs and incubated with either streptavidin - hrp for one hour ( zymed 1 : 4000 , for donkey anti - goat igg stained strips ) or vectastain ab reagent ( avidin dh linked to biotinylated peroxidase ) for 30 minutes ( for horse anti - mouse igg stained strips ). the strips were washed for 30 minutes in pbs and developed using diaminobenzadine tetrahydrochloride ( dab ). the membrane strips were washed for 10 minutes in pbs and air dried . a preliminary western run to test the response of the antibodies was run without controls . antibodies to pdgf and tgf β showed little activity against the inventive composition ( lane 6 pdgf , 7 tgf β ). antibodies to egf , tgf α , fgf α , fgf β , ( lanes 1 - 4 , respectively ) had identical binding to the invention with bands at 70 kda , 32 - 34 kda and 15 - 17 kda . while the specific invention has been described with an emphasis upon preferred embodiments , it will be obvious to those of ordinary skill in the art that variations in the preferred methods of the present invention may be used and that it is intended that the invention may be practiced otherwise than as specifically described herein . accordingly , this invention includes all modifications encompassed within the spirit and scope of the invention as defined by the following claims .	0
fig1 shows a heat exchanger plate 1 . the heat exchanger plate 1 comprises bulges 2 which are raised by a given height over the plane of the heat exchanger plate 1 . furthermore , the heat exchanger plate 1 comprises hollows 3 which are sunk to a given depth in this heat exchanger plate 1 . the bulges 2 are symbolized by white circles while the hollows 3 are symbolized by circles with a cross . as it is known in the art , two such heat exchanger plates 1 form a pair of plates when stacked upon each other . two such neighbouring plates usually will with be slightly differently shaped , such that when they are stacked , the bulge 2 of one plate meets with hollows 3 of the neighbouring plate , etc . flow paths are in this manner formed within such pairs . typically the flow path formed on one side of a heat exchanger plate 1 will belong to a first flow path , and the flow path formed on the opposite side will belong to a second flow path being sealed from the first flow path . the heat exchanger plate 1 is made of sheet metal . a sheet metal is a material having a good thermal conductivity and can be formed in a press or die . it is also possible to use plastic materials as sheet metal . the bulges 2 and the hollows 3 form a three - dimensional structured profile or pattern . this pattern is produced in said press or die . however , any other suitable pattern can be used , e . g . a herringbone pattern , as they are well established in the art . the heat exchanger plate 1 of the illustration comprises four through - openings 5 - 8 . these through - openings 5 - 8 are used to form channels or connections to the first and second flow paths respectively . for example , the through - openings 5 , 7 forms a supply and a return for the first flow path and the through - openings 6 , 8 form a supply and a return for the second fluid path . in order to separate the two flow paths from each other a gasket 9 is introduced between two heat exchanger plates . this is shown in fig2 a , 2 b . fig2 shows three heat exchanger plates 1 a , 1 b , 1 c . to simplify the further explanation the heat exchanger plate 1 b is simply termed as “ heat exchanger plate ” or “ first heat exchanger plate ”. the heat exchanger plate 1 a is termed as “ adjacent heat exchanger plate ” or “ second heat exchanger plate ”. the gasket 9 has a form that a first set of through - openings 5 , 7 is arranged outside a space sealed by the gasket 9 and a second set of through - openings 6 , 8 is arranged within the sealing , thus forming e . g . second flow path . the corresponding gasket between the first heat exchanger plate 1 b and a third heat exchanger plate 1 c is positioned such the openings 5 , 7 are sealed , and the openings 6 , 8 are left free to the external . in this way it is possible to use the through - openings 5 , 7 as supply and return for the first flow path and the through - openings 6 , 8 as supply and return for the second flow path . the gasket 9 is arranged within a groove 10 . this groove is shown in more detail in fig2 . the groove 10 has a inner surface 11 , in the present illustration being a bottom , and two side walls 12 , 13 . two protrusions 14 , 15 of the groove 10 of the first heat exchanger plate 1 b are directed to the adjacent or second heat exchanger plate 1 a . in its opposite or lower side the first heat exchanger plate 1 b comprises two recesses 16 , 17 in the form of which corresponds to the form of the protrusions 14 , 15 which is in the present case a triangle . however , it is possible that only the top of the protrusions is formed as a triangle . when two heat exchanger plates 1 a , 1 b are stacked onto each other and the gasket 9 is positioned in the groove 10 of the first heat exchanger plate 1 b , the gasket 9 is deformed in the region of the protrusions 14 , 15 . this deformation results in a compression of the gasket 9 which is stronger in the region of the protrusions 14 , 15 than in other regions . to this end the protrusions 14 , 15 have a height which ensures a significant deformation of the gasket 9 , such as at least 10 % 25 % of the thickness of the gasket 9 , or more preferably at least 20 %, or even more preferably at least 25 %. the gasket 9 is deformed into the recesses 16 , 17 on the lower side of the second heat exchanger plate 1 a . therefore , the gasket has a wave like form with regions of stronger compression and regions of a less strong compression . the inner surface 11 of the groove 10 is flat between the side walls 12 , 13 and the protrusions 14 , 15 . the bottom 11 of the groove 10 is flat as well as between the protrusions 14 , 15 . in these flat regions ( the lower side of the bottom 11 of the groove 10 is flat as well as in these regions ) have the effect that the gasket 9 is only slightly compressed in these regions as it is known from the art . the effect of the protrusions 14 , 15 is shown in fig2 b . even when the first heat exchanger plate 1 b is deformed under the pressure between the heat exchanger plates 1 a , 1 b the gasket 9 ensures a tight sealing . although the heat exchanger plate 1 b has been deformed , the protrusions 14 , 15 are still positioned within the gasket 9 . the elasticity of the material forming the gasket will just follow the protrusions 14 , 15 still forming a fluid tight barrier . the protrusions 14 , 15 will push at the gasket 9 thus still squeezing it against the second heat exchanger plate 1 a , even at a significant deformation of the heat exchanger plate 1 b . fig3 shows a detail iii of fig1 in a larger scale without the gasket 9 . it can be seen that the protrusions 14 , 15 in the groove 10 are restricted to a section of the groove 10 surrounding the through - opening 5 partly . therefore , the protrusions 14 , 15 run along a curved path thus strengthening the heat exchanger plate 1 . the groove 10 has at least a linear section 18 , 19 running along the edges of the heat exchanger plate 1 . the protrusions 14 , 15 are restricted to an area out of said linear sections 18 , 19 . in fig4 a slightly modified embodiment is shown . the same elements have the same reference numerals . in fig4 the gasket is not shown . auxiliary protrusions 20 are arranged in the groove 10 . these auxiliary protrusions 20 traverse the groove 10 orthogonal to the protrusions 14 , 15 . these auxiliary protrusions 20 serve to strengthen the heat exchanger plate 1 in the orthogonal direction too . fig5 shows an alternative embodiment where the grooves 10 instead are ‘ up - wards ’ hollows within the walls 12 , 13 forming a raised section , the inner surface 11 being a top . the gasket 9 then rests on this raised section , being the top 11 of the raised section of the lower heat exchanger plate , and this lower section then has protrusions 14 , 15 reaching into the hollows forming the grooves 10 , thus pressing the gaskets 9 into the hollows deforming it as described above . any of the embodiments of the fig1 - 4 also applies to this embodiment of fig5 . while the present invention has been illustrated and described with respect to a particular embodiment thereof , it should be appreciated by those of ordinary skill in the art that various modifications to this invention may be made without departing from the spirit and scope of the present .	5
referring to fig1 , the vehicle seat 10 is supported on a frame 12 , and includes foam cushions 14 and 16 on the seat bottom and back . the seat 10 is equipped with a conventional shoulder / lap seat belt 18 anchored to the vehicle floor ( not shown ) and b - pillar 20 . in use , the belt 18 is drawn around an occupant or through the frame of a child or infant seat , and a clip 22 slidably mounted on the belt 18 is inserted into the buckle 24 to fasten the belt 18 in place . a retractor assembly ( not shown ) mounted in the b - pillar 20 maintains a desired tension on the belt 18 , and locks the belt 18 in place when the vehicle experiences significant deceleration . according to this invention , the presence of a rfis on the seat cushion 14 is detected based on the operating state and tension of the seat belt 18 , and the position of the seat belt 18 relative to a bight region 26 where the seat bottom and back cushions 14 , 16 meet . the operating state of the seat belt 18 — i . e ., buckled or un - buckled — is detected by a switch within the buckle 24 that is closes or opens on insertion of the clip 22 into the buckle 24 . one side of the switch is connected to an electrical ground or power terminal , while the other side is coupled to the conductor 28 to provide an electrical signal ( state ) indicative of the belt state . the seat belt tension is detected by a belt tension sensor 30 that may be located in the b - pillar 20 as shown , near the floor on the outboard side of seat 10 , or in any other convenient location . the tension sensor 30 may be constructed as disclosed , for example , in the aforementioned u . s . pat . no . 6 , 605 , 877 to patterson et al ., incorporated herein by reference , and produces an electrical signal ( tension ) on line 32 indicative of the seat belt tension . the proximity of the seat belt 18 relative to the bight region 26 is detected magnetically using a seat belt magnetic strip 34 a and a first hall effect seat sensor 36 . the first hall effect sensor 36 is disposed in the seat back or bottom cushion 14 , 16 in the vicinity of the central portion of the bight region 26 , and the magnetic strip 34 a is embedded in the fabric of the seat belt 18 . when the seat belt 18 is in proximity to the central portion of the bight region 26 as shown in fig1 , the strip 34 a is magnetically coupled with the sensor 36 , and an electrical signal ( pos 1 ) produced by sensor 36 on line 38 indicates that the seat belt 18 is near the bight region 26 ; in other positions of the seat belt 18 , there is only weak magnetic coupling between the strip 34 a and the sensor 36 , and the pos 1 signal indicates that the seat belt 18 is disposed away from the bight region 26 . optionally , a second hall effect sensor 40 is disposed in the middle of the seat back cushion 16 , and detects proximity of the seat belt 18 to the seat back cushion 16 by virtue of a magnetic strip 34 b embedded in the fabric of the seat belt 18 . when the seat belt 18 is in proximity to the back cushion 14 as shown in fig1 , the strip 34 a is magnetically coupled with the sensor 40 , and an electrical signal ( pos 2 ) produced by sensor 40 on line 42 indicates that the seat belt 18 is close to the back cushion 16 ; in other positions of the seat belt 18 , there is only weak magnetic coupling between the strip 34 b and the sensor 40 , and the pos 2 signal indicates that the seat belt 18 is disposed away from the back cushion 16 . the magnetic strips 34 a and 34 b may be constituted by individual lap and shoulder portions as shown , or by a single continuous strip of magnetic material if desired . in any event , portions of the seat belt 18 containing the magnetic strips 34 a and 34 b will be in proximity to the first and second sensors 34 and 40 when a rfis is present , much the same as when the seat belt 18 is buckled with an empty seat as depicted in fig1 ; and no part of the seat belt 18 will be in proximity to the sensors 34 or 40 when the seat belt 18 is used to properly secure a normally seated person or a forward - facing infant seat . the electrical signals on lines 28 , 32 and 38 ( and optionally , line 42 ) are provided as inputs to a passive occupant detection system electronic control unit ( pods ecu ) 50 , which in turn , is coupled to an airbag control module ( acm ) 52 via bi - directional communication bus 54 . the acm 52 may be conventional in nature , and operates to deploy one or more airbags or other restraint devices ( not shown ) for vehicle occupant protection based on acceleration data and occupant characterization data obtained from pods ecu 50 . in general , acm 52 deploys the restraints if the acceleration signals indicate the occurrence of a severe crash , unless the pods ecu 50 indicates that a rfis is present . also , acm 52 communicates the suppression status and driver warnings to a driver display device 56 . in general , the pods ecu 50 characterizes the inputs on lines 28 , 32 and 38 ( and optionally , line 42 ), and applies them to a decision matrix such as depicted by the chart of fig3 to determine if a rfis is present . the flow diagram of fig2 represents a software routine that is periodically executed by the pods ecu 50 according to this invention . the block 60 is first executed to read the inputs including the seat belt tension ( tension ), the seat belt status ( status ), and the seat belt position ( pos 1 ). as indicated above and explained below , the inputs may optionally include the position signal pos 2 . the block 62 then characterizes the analog inputs ( tension and pos 1 ) by comparing them to various predefined thresholds , and applies the inputs to the decision matrix of fig3 . in the illustrated embodiment , tension is characterized as being either high ( above a tension threshold ) or low ( below the tension threshold ), and the position pos 1 of the seat belt relative to the bight area of the seat is characterized as being either near ( above a proximity threshold ) or far ( below a proximity threshold ). the decision matrix of fig3 provides an rfis present output ( yes or no ) and a driver warning output , and the block 64 causes the pods ecu 50 to supply the outputs to acm 52 . the acm 52 allows or suppresses air bag deployment based on the supplied outputs , and visually communicates the occupant status and any driver warnings via display 56 . referring to fig3 , the decision matrix of the illustrated embodiment comprehends the eight possible output combinations of tension , status and pos 1 . states 1 and 2 result in a yes condition of the rfis present output ; in each case , status = buckled and pos 1 = near . in state 1 , tension = high , and no driver warning is produced ; in state 2 , tension = low , and a driver warning ( warning 1 ) is produced to indicate that the seat belt tension should be increased in order to properly restrain the infant seat . state 1 can also occur when the seat 10 is occupied by a normally seated person while the seat belt 18 buckled but positioned behind the occupant ; accordingly , the driver warning ( warning 1 ) should be broad enough to encompass either an improperly tensioned infant seat or an improperly restrained but normally seated person . the other states ( 3 – 8 ) result in a no condition of the rfis present output , because status = unbuckled and / or pos 1 = far . in systems where the seat belt position signal pos 2 is provided as an additional input , the decision matrix may detect additional conditions of improper seat belt usage by a normally seated person . for example , an occupant may be utilizing the lap portion of the seat belt 28 properly , with the shoulder portion of the seat belt 28 improperly disposed between the occupant and the seat back cushion 16 ; in this case , pos 1 = far but pos 2 = near . if this combination of position inputs occurs while status = buckled , the pods ecu 50 may issue a suitable driver warning . another improper condition can also occur when an occupant is improperly sitting on the lap portion of the seat belt 28 , with the shoulder portion of the seat belt 28 properly positioned in front of the torso ; in this case , pos 1 = near but pos 2 = far . this has the benefit of distinguishing between an improperly tensioned infant seat and a normally seated but improperly belted occupant . in summary , the present invention provides a simple and cost - effective way of reliably detecting the presence of a rfis without requiring special equipment on the infant seat . the addition of the optional seat back belt proximity sensor provides further occupant detection capability , and the ability to distinguish between an improperly tensioned infant seat and a normally seated but improperly belted occupant . while the present invention has been described with respect to the illustrated embodiment , it is recognized that numerous modifications and variations in addition to those mentioned herein will occur to those skilled in the art . for example , the system may include additional sensors if desired , or a proximity sensor other than a hall effect sensor , and so on . accordingly , it is intended that the invention not be limited to the disclosed embodiment , but that it have the full scope permitted by the language of the following claims .	1
the following detailed description is merely exemplary in nature and is not intended to limit the invention or the application and uses of the invention . furthermore , there is no intention to be bound by any expressed or implied theory presented in the preceding technical field , background , brief summary or the following detailed description . the words “ rest ” or “ pause ” or “ retracted ” are used interchangeably herein to refer to the position or status of the wipers generally when motion is temporarily stopped during intermittent operation and the word “ stowage ” is used generally to refer to the wiper position or status when the wipers are off . fig3 - 4 are simplified representations of the windshield wiping - washing and wiper de - icing system 50 of the present invention for different wiper arm positions 34 , 35 . in fig3 , wiper assemblies 24 , 24 ′ are shown in standard wiping - washing state 34 , similar to that shown in fig1 , that is , wiper assemblies 24 , 24 ′ are up on the windshield moving according to arrows 32 , 32 ′ and emitting washing fluid sprays 30 . this is analogous to the normal wiping - washing mode illustrated in fig1 . however , system 50 differs from prior art system 20 in that , among other things , auxiliary de - icing spray nozzles 36 , 36 ′ are provided . auxiliary de - icing spray nozzles 36 , 36 ′ spray wiper assemblies 24 , 24 ′ when they are in pause or stowage position 35 illustrated in fig4 . the washer fluid emitted as sprays 37 , 37 ′ contains an antifreeze compound and therefore acts to melt ice that has accumulated on wiper assemblies 24 , 24 ′. when wiper assemblies 24 , 24 ′ are in retracted or stowage position 35 , windshield washing sprays 30 are desirably turned off , but this is not essential . fig5 - 6 are simplified schematic piping diagrams of windshield wiping - washing and wiper de - icing system 50 of the present invention showing further details and illustrating washing fluid flow during different modes of operation . for clarity , the details of wiper arm spindle 25 , wiper arm 26 , wiper blade support bracket 27 and wiper blade 28 are omitted in fig5 - 6 . as shown in fig5 - 6 , system 50 of the present invention includes washing fluid reservoir 52 , washing fluid pump 54 , valve 56 , and : ( i ) tubing or conduit 57 leading to wiper assemblies 24 , 24 ′ with spray nozzles 29 emitting washing fluid sprays 30 ( see fig5 ), and ( ii ) tubing or conduit 58 leading to nozzles 36 emitting washing fluid sprays 37 ( see fig6 ). for convenience of explanation and not intended to be limiting , it is assumed that wiper assembly 24 ′ is like assembly 24 and operates in substantially the same way and likewise for nozzles 36 ′, 36 and sprays 37 ′, 37 . for convenience of description , unless otherwise expressly indicated , reference numbers 24 , 36 , 37 are intended to include their primed equivalents 24 ′, 36 ′, 37 ′. in fig5 - 6 heavier dark lines are used to illustrate the paths followed by windshield washing fluid 53 from reservoir 52 , through pump 54 and valve 56 to wiper assembly spray nozzles 29 in fig5 or auxiliary de - icing spray nozzles 36 in fig6 . fig5 illustrates washing fluid flow during normal wiping - washing mode of operation . in fig5 washing fluid 53 flows from pump 54 through valve 56 through channel 57 to wiper assembly 24 and nozzles 29 , which produce sprays 30 . fig6 illustrates the arrangement of parts and washing fluid flow during the wiper de - icing operation of the present invention . in fig6 washing fluid 53 flows from reservoir 52 through pump 54 , through valve 56 and conduit 58 to nozzles 36 , which produce sprays 37 . nozzles 36 are arranged with respect to wiper assembly 24 in retracted or rest position 35 so as to maximize coverage of wiper assemblies 24 by sprays 37 , especially coverage of support brackets 27 and blades 28 where ice formation can have the largest impact . in fig5 - 6 valve 56 is assumed to be a two position exclusive or valve , that is , washing fluid 53 flows either to nozzles 29 or nozzles 36 but not to both nozzles 29 and 36 at the same time . however , this is merely for convenience of description and not intended to be limiting . persons of skill in the art will understand based on the description herein that valve 56 may , alternatively , be such that washing fluid 53 flows to nozzles 29 for sprays 30 whenever pump 54 is on and that valve 56 only switches on and off sprays 37 . either arrangement is useful . still further , persons of skill in the art will understand based on the description herein that valve 56 may embody two independent valves , one for nozzles 36 and sprays 37 and another for nozzles 29 and sprays 30 , but this is not essential . a dual valve arrangement has the advantage of flexibility of operation since sprays 30 and 37 may be independently controlled . in the preferred mode of operation sprays 37 come on when wiper assembly 24 is in retracted position 35 and sprays 30 come on when wiper assembly 24 is in wiping position 34 and the user has activated the “ wash ” mode switch . fig7 is a simplified electrical schematic diagram of control system 70 useful for wiping - washing and wiper de - icing system 50 of the present invention . system 70 comprises washer - on switch 72 ( the “ wash ” mode switch ) coupled to controller 74 by bus or leads 73 , memory 76 coupled to controller 74 by bus or leads 75 , temperature sensor 78 coupled to controller 74 by bus or leads 77 , washer fluid pump switch 80 coupled to controller 74 by bus or leads 81 , wiper actuator 82 coupled to controller 74 by bus or leads 83 , de - ice valve activator 84 coupled to processor 74 by bus or leads 85 and wiper position sensor 86 coupled to processor 74 by bus or leads 87 . wiper actuator 82 and wiper position sensor 86 may be integrated in the same housing or interconnected as shown by bus or leads 89 . washer - on switch 72 is what the operator uses to initiate a windshield washing operation , that is , to launch a wash cycle or wash mode . memory 76 stores operating programs ( e . g ., see fig7 ), predetermined constants ( e . g ., t 1 , tp , tc , etc .) and intermediate variable values used by controller 74 of control system 70 in operating system 50 . pump switch 80 energizes pump 54 of fig5 - 6 . controller 74 manages overall operation of washer / wiper / de - icing system 50 . wiper actuator 82 , e . g ., a motor or motor assembly , causes wiper assembly 24 to move across windshield 22 in directions 32 and return to rest , pause and / or stowage position 35 , under the control of controller 74 . de - ice valve activator 84 opens and closes valve ( s ) 56 and wiper position sensor 86 monitors or determines the position of wiper assembly 24 , that is , whether it is in wiping position 34 or in retracted or stowage position 35 . person of skill in the art will understand that the pause or rest position of wiper assembly 24 may be somewhat different than the stowage position . in general , in the rest or pause position , assembly 24 usually does not retracted as far toward or at the base of the windshield as in the stowage position . for the purposes of this invention , nozzles 36 may be located so that sprays 37 contact wiper assemblies 24 in either the pause or stowage positions or both according to the needs of the designer . persons of skill in the art will also understand that different types valves may be used for valve ( s ) 56 and , as used herein , the words “ de - ice valve actuator 84 ” are not intended to be limiting and are intended to include any type of mechanism as may be appropriate to operate the type of valve ( s ) 56 being used . the operation of system 70 will be more fully understood by reference to fig8 . control system 70 may be a fully software programmable system wherein program instructions are stored in memory 76 and executed by controller 74 or it may be a hardwired logic system or a combination thereof control system 70 may be a dedicated controller substantially dealing only with washing / wiping / de - icing system 50 or may be part of an overall or shared vehicle electronic system dealing with system 50 on a part time basis , or a combination thereof the various elements of system 70 may be dumb , that is , operating entirely under the direction of controller 74 or may be smart , that is , containing some logical functions and / or timers . the various elements in system 70 may operate under the general direction of controller 74 but provide certain sub - functions ( e . g ., timing , critical value comparisons , etc .) on their own . either arrangement is useful . various time intervals or time durations mentioned herein , e . g ., t 1 , tp , etc . may be measured using software loops or other programmable means or may be measured by separate hardware timers or combinations thereof . for example , dry - mode time duration t 1 may be determined by controller 74 or may be determined by a timer built actuator 82 or elsewhere and the signals sent by controller 74 to operate actuator 82 adapted accordingly . any and all of these variations are useful and persons of skill in the art will understand based on the description herein how to implement them depending upon the needs of their particular application . fig8 is a simplified process flow chart of method 100 of operating wiping - washing and wiper de - icing system 50 of the present invention , according to a preferred embodiment . method 100 is executed by control system 50 of fig7 in combination with reservoir 52 , pump 54 and valve ( s ) 56 of fig5 - 6 . method 100 begins with start 102 that desirably occurs at vehicle power - up , that is , when system 70 is energized when the vehicle is turned on . system 70 and method 100 are quiescent until the operator or other vehicle operator pushes or otherwise activates switch 72 to initiate a wash cycle , whereupon wash switch on ? query 104 results in a yes ( true ) outcome . ( prior to that query 104 returns a no ( false ) outcome and loops back to start 102 .) method 100 then progresses to start pump step 106 wherein , for example , controller 74 retrieves a “ start wash ” signal from switch 72 and sends an appropriate signal over bus or leads 81 to pump switch 80 thereby causing washing fluid pump 54 to start pumping fluid 53 from reservoir 52 through washing / de - icing system 50 . this initiates the windshield washing process . as will be subsequently explained , washing fluid pump stays on as long as the operator continues to activate switch 72 . following start pump step 106 , method 100 executes outside temp & gt ; tc ? query 108 wherein it is determined whether or not the outside air temperature measured by temperature sensor 78 is greater than a predetermined critical tc . tc is the temperature at which there is a significant probability of ice formation on wiper assembly 24 , and is generally in the range of 0 ° c . to − 39 ° c ., usually about 0 ° c . to − 20 ° c . and more likely about − 7 ° c . however , some ice formation may occur even though the average ambient temperature is ≧ 0 ° c . because heat loss from evaporation may lower the temperature of residual water on wiper assembly 24 or wiper assembly 24 itself to below 0 ° c . therefore , setting tc in the range about + 5 ° c . to − 5 ° c . is convenient , with about 0 ° c . preferred . tc may be retrieved from memory 76 by controller 74 or may be stored in sensor 78 . either arrangement is useful . if the outcome of query 108 is yes ( true ) meaning that the outside air temperature is high enough that ice formation on wiper assembly 24 is unlikely , then method 100 proceeds to steps 110 - 118 . steps 110 - 118 are analogous to conventional wash cycle steps 64 - 68 , respectively . ww on in windshield wash mode step 110 is executed . ( the abbreviation “ ww ” stands for “ windshield wiper ”.). step 110 causes the wipers to begin moving across the windshield , usually in a low speed mode , suitable for a wash cycle . wash switch still on ? query 112 is then executed to determine whether the operator is still activating the “ wash ” switch . if the outcome of query 112 is yes ( true ) then method 60 loops back as shown by path 112 a and the pump and windshield wipers remain on . if the outcome of query 112 is no ( false ), then stop pump step 114 is executed and the washing fluid pump shuts off , thereby terminating spraying of the windshield with washing fluid . the combination of steps 106 - 114 cause nozzles 29 to emit washing fluid spray 30 onto the windshield as long as the operator is activating the “ wash ” switch and the ambient temperature t & gt ; tc . after stop pump step 114 washing fluid no longer flows to nozzles 29 and ww on in windshield dry mode for time t 1 step 116 is executed to dry the windshield for time duration t 1 . in step 116 the windshield wipers may be left in the same mode set in step 110 or changed to a different operating mode . the duration t 1 may be selected by the designer , depending upon the particular vehicle &# 39 ; s requirements . approximately 10 seconds is a non - limiting example of a useful time duration for t 1 , but larger or smaller values can also be used . following the expiration of time duration t 1 , method 100 executes return ww to prior mode step 118 whereby it returns operation of the wipers to whatever state or mode they were in prior to initial query 104 . method 100 then returns to start 102 and initial query 104 as shown by path 119 . most modern wiper systems can operate continuously at various speeds or in a pause or delay mode . in the delay mode , wiper assembly 24 operates in wiping position 34 for a predetermined wiping time and pauses in rest position 35 for a predetermined ‘ pause ’ time tp , and then repeats the sequence wipe - pause - wipe , etc . returning now to query 108 , if the outcome of query 108 is no ( false ), then method 100 proceeds to ww on in de - ice mode step 120 . the de - ice mode is preferably a minimum pause time operating mode , that is tp has its smallest value . pause time tp may , for example , be retrieved by controller 74 from memory 76 or maybe built into actuator 82 or a combination thereof . either arrangement is useful . minimum pause times tp are conveniently in the range of 0 to 2 seconds , typically in the range of 0 . 1 to 1 seconds and preferably in the range of 0 . 25 to 0 . 50 seconds . following step 120 , system 50 prepares to de - ice wiper assemblies 24 by executing ww moving ? query 122 . in step 122 , system 70 determines whether wiper assembly 24 is moving or not , e . g ., stuck in the ice or temporarily paused . if the outcome of query 122 is yes ( true ) indicating that wiper assemblies 24 are moving , then method 100 proceeds to step 124 . in step 124 if de - ice valve 56 is already open to permit washer fluid 53 to flow to nozzles 36 , then valve 56 is closed . if valve 54 is already closed , then in step 124 , it remains closed . this is accomplished by controller 74 sending an appropriate signal to de - icing valve activator 84 controlling valve ( s ) 56 . if the outcome of query 122 is no ( false ) indicating that wiper assemblies 24 are not moving , e . g ., one or both of assemblies 24 , 24 ′ are held fast by ice or in a temporary pause , then in step 126 , de - icing valve activator 84 is energized to open valve 56 causing washer fluid 53 to flow to nozzles 36 so that sprays 37 are directed toward wiper assemblies 24 while in retracted or paused position 35 . following steps 124 or 126 , wash switch still on ? query 128 is executed wherein controller 74 determines the state of switch 72 ( or 80 ). if the outcome of query 128 is no ( false ) indicating that the operator has released switch 72 , then method 100 proceeds to stop pump step 114 , ww on in windshield dry mode for time t 1 step 116 , return ww to prior mode step 118 and return to start 102 via path 119 , as already discussed . if the outcome of query 128 is yes ( true ) indicating that the operator has ‘ wash ’ switch 72 ( and therefore pump switch 80 ) still activated , then method 100 loops back to step 122 as shown by path 129 . as long as the operator continues to depress or otherwise activate switch 72 , method 100 will activate sprays 37 whenever wiper assemblies 24 are paused or stuck in position 35 and thereby provide de - icing fluid to assemblies 24 . there are two scenarios of interest : first , if wiper assembly 24 is frozen , unable to move and is stuck in the pause or rest or stowage position , method 100 continues to bathe wiper assembly 24 in washing fluid de - icing spray 73 as long as switch 72 is activated ; and second , if wiper assembly 24 can move and shuttle back and forth in the direction of arrows 32 , then in the de - ice mode provided by step 120 , each time wiper assembly 24 stops in pause or rest position 35 , valve 56 opens in response to step 126 and wiper assemblies 24 are bathed with washing fluid de - icing spray 73 during the pause interval . this serves to retard or prevent further ice buildup when the wipers are operating in cold weather conditions . method 100 continues around this loop ( steps 120 , 122 , 124 / 126 , 128 ) until the operator releases switch 72 and pump 54 shuts off in step 114 . then , as already discussed , method 100 proceeds to ww on in windshield dry mode for time t 1 step 116 , return ww to prior mode step 118 and then returns to start 102 as shown by path 119 . in the preferred embodiment , the operator controls the amount of windshield washer fluid by maintaining the switch 72 in the active position , but this is not essential . alternatively , controller 74 or the vehicle computer can control the amount of windshield washer fluid delivered during the wash cycle and / or the de - ice cycle . this has the advantage that the state of the vehicle can be used to determine the time required for the various steps executed in method 100 . for example and not intended to be limiting , the pump - on time and the wash and / or de - ice time can be made dependant on vehicle geometry , vehicle speed , wind speed , wiper speed , wiper motor feedback , windshield size , pump flow , ambient temperature , wash fluid composition , washer fluid temperature , other factors and / or combinations thereof this allows the system to deliver an appropriate amount of fluid and wiper and / or de - ice cycle times as function of the current vehicle state . for example , when the vehicle is parked , the de - ice mode spray interval and the wipe intervals can be lengthened to help combat accumulating snow or other adverse conditions . while at least one exemplary embodiment has been presented in the foregoing detailed description , it should be appreciated that a vast number of variations exist . for example , while operation of system 50 has been described in terms of nozzles 29 being mounted on wiper assemblies 24 , this is not essential . alternatively , nozzles 29 may be mounted on the vehicle itself , for example , at the periphery of windshield 22 and spray onto windshield 22 during the windshield washing cycle before or during wiper motion 32 . either arrangement is useful . it will also be noted that , in contrast to prior art wiper de - icing arrangements such as are described for example in u . s . pat . no . 6 , 438 , 789 b1 , nozzles 36 are preferably fixed and that a pop - up blade de - icing arrangement is not necessary . this significantly simplifies blade de - icing and is a significant advantage over the prior art . it will be further noted that although in the preferred embodiment sensor 78 is used to measure ambient air temperature t and query 108 is executed in preferred method 100 to determine whether t & gt ; tc , this is not essential . the present invention will also operate if temperature sensor 78 is omitted and query 108 is replaced with a timing or randomizing step that toggles method 100 between branches 110 - 112 and branch 120 - 128 ( the branches rejoin at step 114 ) at periodic or random intervals . some washing fluid will be wasted when freezing is unlikely , but this alternative arrangement provides a useful backup in case sensor 78 fails . it should also be appreciated that the exemplary embodiment or exemplary embodiments are only examples , and are not intended to limit the scope , applicability , or configuration of the invention in any way . rather , the foregoing detailed description will provide those skilled in the art with a convenient road map for implementing the exemplary embodiment or exemplary embodiments . it should be understood that various changes can be made in the function and arrangement of elements without departing from the scope of the invention as set forth in the appended claims and the legal equivalents thereof	1
a magnetic separation device 10 to separate non - magnetic components from magnetic components in a wet or dry mixture , as shown in fig1 - 5 , the device comprising a non - magnetic cylindrical housing 20 defining an inner longitudinal cylindrical channel 22 , an outer surface 24 , a central radial hilt 30 , a closed end tool section 25 and a handle section 27 defining an opening 29 to the inner longitudinal channel 22 , a handle section grommet 40 having a central aperture 42 , the handle section grommet 40 inserting within the opening 29 of the handle section 27 , a drive shaft 60 defining a tool end 62 , a cylindrical neck 64 and a drill attaching end 66 , the tool end 62 attaching a strong cylindrical bipolar magnet 50 encased within a slip sleeve 55 , the slip sleeve 55 slidably engaged within the inner longitudinal cylindrical channel 22 , the drill attaching end 66 extending beyond the central aperture 42 of the handle section grommet 40 further secured to a rotary drive apparatus a , fig1 , delivering rotation to the 60 drive shaft , the bipolar magnet 50 upon the tool end 62 rotating within the inner longitudinal cylindrical channel 22 of the cylindrical housing 20 and being movable between the tool section 25 and the handle section 27 as drive shaft 60 is pulled or pushed with the neck 64 moving within the central aperture 42 of the grommet 40 , the bipolar magnet 50 producing an alternating and rotating magnetic field around the outer surface 24 of the cylindrical housing 20 attracting magnetic components from a mixture of magnetic and non - magnetic particles against the outer surface 24 of the cylindrical housing 20 , spinning the particle mixture upon the outer surface 24 of the tool section 25 of the cylindrical housing 20 while the bipolar magnet 50 is positioned within the tool section 25 , fig2 . this spinning action urges , liberates and releases the non - magnetic particles outward while spinning , grinding and agitating the magnetic particles against one another while rotating upon the outer surface 24 , wherein the non - magnetic particles are expelled and collected from the spinning mixture while the magnetic particles remain bound to the outer surface 24 at the tool section 25 of the cylindrical housing 20 . once the user has cleaned the quantity of mixed materials to their satisfaction , the device 10 is then transferred to a disposal location where the magnetic material is removed from the outer surface 24 of the tool section 25 of the cylindrical tube 20 by withdrawing the bipolar magnet 50 by sliding the drive shaft 60 from the tool section 25 into the handle section 27 , fig3 , the magnetic material removed from the outer surface 24 as the bipolar magnet 50 is passed by the radial hilt 30 into the handle section 27 , withdrawing the magnetic attraction retaining the magnetic material from the tool section 25 , the radial hilt 30 blocking the magnetic material from transfer onto the outer surface 24 of the handle section 27 within which the bipolar magnet 50 is now positioned . it would be beneficial for the cylindrical housing 20 to be made of a smooth , non - stick material for ease of removal of the magnetic materials from the tool section 25 during disposal . the device 10 is then ready for further use in processing more of the mixture , or reprocessing the same material for more complete separation by returning the bipolar magnet 50 to the tool section 25 of the cylindrical housing , fig2 . the slip sleeve 55 surrounding the bipolar magnet 50 is made of a non - magnetic friction reducing material which allows the encased bipolar magnet 50 to rotate and slide freely within the inner longitudinal cylindrical channel 22 . the bi - polar magnet 50 is a strong earth magnet having a positive portion n and a negative portion s which may be provided in several polar configurations embodiments including a radial polar and a diametric polar configuration , as shown in fig4 and 5 . this bi - polar magnet 50 would configure the positive portion n and negative portion s in a manner which would produce a shifting or alternating magnetic field during rotation . this rotation causes the magnetic particles to also rotate around the outer surface of the cylindrical housing 20 at the same speed as the rotary drive apparatus a would turn the attached drive shaft 60 . the higher the rotational speed of the drive shaft 60 , the greater the rotational speed of the bipolar magnet 50 and its resulting alternating magnetic field , further causing greater rotation and grinding movement of the magnetic particles , separating the non - magnetic particles from confinement within the magnetic particles and producing a greater amount of rotational force or inertia upon the non - magnetic particles , spinning those non - magnetic particles outward and releasing them from the mixture , preferably into a container for further processing . the retained magnetic particles are then transferred to an appropriate waste disposal container while still attached upon the device 10 and released from the device 10 into the waste disposal container by withdrawing the bipolar magnet 50 within the cylindrical housing 20 from the tool section 25 to the handle section 27 thereby removing the magnetic attraction from the tool section 25 . the radial hilt 30 would be attached to the outer surface 24 of the cylindrical housing 20 along a linear axis between the tool section 25 and the handle section 27 introducing a barrier between the tool section 25 and handle section 27 and also a hand grip stop for the user to hold during operation and use , with the positioning of the radial hilt 30 dependant on the manufactured length desired for the tool section 25 . it is contemplated that the radial hilt 30 may be incorporated into a handle section sleeve 28 which inserts over the outer surface 24 of the handle section 27 of the cylindrical housing 20 , fig3 and 4 , the handle section sleeve 28 being also made of a non - magnetic material and could also be constructed with the radial hilt 30 as an integrated component . as currently constructed , the tool section 25 beyond the radial hilt 30 is provided in a short version and a long version , with the handle section 27 being provided in both versions at approximately the same size and length . the radial hilt 30 would further provide a tool side surface 32 and a handle side surface 34 , with the radial hilt 30 aligning the tool side surface 32 and handle side surface 34 at right angles with the outer surface 24 , as shown in fig2 and 3 , for better deterrent to the passage of magnetic materials during withdrawal of the bipolar magnet 50 from the tool section 25 to the handle section 27 of the cylindrical housing 20 . it is contemplated within the scope of this device 10 that its use may be in conjunction with mining and prospecting , ideally suited for use in the separation of black sand mixtures containing precious metals , and also in applications involving plastics and foundries , oil and petroleum refinement , oil and petroleum extraction , chemical and pharmaceutical processing , agricultural and food processing or any other industrial use requiring the separation or extraction of magnetic particles . additionally , the rotary drive apparatus a may be proportionally sized to the application employed , from as small as the hand held rotary drill shown in fig1 , above , to an independent drive mechanism , not shown , which is supplied to the device or provided locally within the industrially application or appliance to compel the required rotational force and speed . a mechanical means , also not shown , may also be provided within a large industrial section to move the magnet from the tool section to the handle section , not under human hand control as is implied in the present device employing the hand held drill of fig1 , the handle section 27 alternatively being referenced as a base section , an anchor section , or a dormant section , depending on the size of the magnet , its orientation and the magnitude of the correlating components . it is contemplated that the device 10 may be used in conjunction with other mining and prospecting application , such as incorporation of the device into a trammel , wet or dry sluice , roller cage , swarf , air or water spinning devices , barrels or drums , or into a conveyor drive mechanism , as observed in the prior art and as determined by those skilled in the art who might substitute the novel features of the current device into other technologies . additionally , the cylindrical housing 20 is intended to be used as a hand held device , held in one hand against the handle side surface 34 by the handle section 27 , with the other hand being used to operate the rotary drive apparatus a while controlling the position location of the bipolar magnet 50 within the longitudinal cylindrical channel 22 . it is essential that the cylindrical housing 20 be of an appropriate circumference to be comfortably and securely held by a user . thus , the cylindrical housing 20 may be presented in more than one circumference for the comfort to various users , with the bipolar magnet 50 and other components accordingly sized to maintain the intended function of the device 10 . the cylindrical bi - polar magnet 50 would preferably be no longer than the length of the tool section 25 , the tool side surface 32 of the radial hilt 30 imposing a separation barrier between the tool section 25 of the cylindrical housing 20 and the handle section 27 of the cylindrical housing 20 , while completely withdrawing any magnetic attraction to the tool section 25 when the bipolar magnet 50 is completely withdrawn into the handle section 27 to release the magnetic particles from the tool section 25 , fig3 . without the radial hilt 30 , the magnetic particles would simply pass along the cylindrical housing 20 without the ability to release the magnetic particles from the cylindrical housing 20 . with the inclusion of the radial hilt 50 , the attracted and attached magnetic particles are prevented from passing along the cylindrical housing 20 and , when the bipolar magnet 50 is withdrawn past the radial hilt 30 , the magnetic particles are released and fall away from the outer surface 24 of the cylindrical housing 20 . while the separation device 10 has been particularly shown and described with reference to a preferred embodiment thereof , it will be understood by those skilled in the art that changes in form and detail may be made therein without departing from the spirit and scope of the invention .	1
in the following detailed description of the preferred embodiments , reference is made to the accompanying drawings which form a part hereof , and in which is shown by way of illustration specific embodiments in which the invention may be practiced . it is to be understood that other embodiments may be utilized and structural changes may be made without departing from the scope of the present invention . some portions of the detailed descriptions which follow are presented in terms of algorithms and symbolic representations of operations on data bits within a computer memory . these algorithmic descriptions and representations are the means used by those skilled in the data processing arts to most effectively convey the substance of their work to others skilled in the art . an algorithm is here , and generally , conceived to be a self - consistent sequence of steps leading to a desired result . the steps are those requiring physical manipulations of physical quantities . usually , though not necessarily , these quantities take the form of electrical or magnetic signals capable of being stored , transferred , combined , compared , and otherwise manipulated . it has proven convenient at times , principally for reasons of common usage , to refer to these signals as bits , values , elements , symbols , characters , terms , numbers , or the like . it should be borne in mind , however , that all of these and similar terms are to be associated with the appropriate physical quantities and are merely convenient labels applied to these quantities . unless specifically stated otherwise as apparent from the following discussions , it is appreciated that throughout the present invention , discussions utilizing terms such as “ processing ” or “ computing ” or “ calculating ” or “ determining ” or “ displaying ” or the like , refer to the action and processes of a computer system , or similar electronic computing device , that manipulates and transforms data represented as physical ( electronic ) quantities within the computer system &# 39 ; s registers and memories into other data similarly represented as physical quantities within the computer system memories or registers or other such information storage , transmission or display devices . [ 0022 ] fig1 illustrates a medical device system 10 with the inventive parameter interaction detection and display feature . medical device system 10 includes a medical device 12 and a programmer 14 . programmer 14 includes an input device 16 and a display 18 and is connected to medical device 12 via communications link 20 . communications link 20 may embody any form of communications protocol , including wired , wireless , optical and other forms of communication protocols . input device 16 , display 18 and the underlying hardware and software make up the programming interface . features of medical device 12 are displayed on display 18 and may be modified through the use of input device 16 . parameter interactions between these features are also displayed on display 18 in the manner described below . [ 0024 ] fig2 illustrates a medical device system 30 with the inventive parameter interaction detection and display feature . medical device system 30 includes a medical device 32 with a built - in programming interface 34 . programming interface 34 includes an input device 36 and a display 38 . features of medical device 32 are displayed on display 38 and may be modified through the use of input device 36 . parameter interactions between these features are also displayed on display 38 in the manner described below . in one embodiment , medical device system 10 is an implantable shock therapy system . such a medical device system 10 is shown in fig3 . in fig3 medical device system 10 includes a defibrillator 40 , a power supply 42 and a programmer 44 . power supply 42 is connected to defibrillator 40 and supplies power to defibrillator 40 . defibrillator 40 is connected to programmer 44 via communications link 20 . in one such embodiment , defibrillator 40 includes a telemetry system 46 for communicating with programmer 44 . in addition , defibrillator 40 supplies the requisite therapy to the heart via leads 48 . programmer 44 includes an input device 52 such as a keyboard or mouse , a display 54 and telemetry system 55 . features selected or programmed by physicians into programmer 44 are communicated through telemetry to defibrillator 40 , where they control shock and pacing therapy applied to the patient &# 39 ; s heart . in one embodiment , systems 10 and 20 include interactive programming feedback . interactive programming feedback is a feature that is designed to assist the user in programming the medical device appropriately . in one such embodiment , a set of rules govern the universe of possibilities that the various parameters may be programmed to . the rules ensure that incompatibilities among features are caught and prevented and that programming conflicts cannot exist . in one such embodiment , if a user programs a parameter in such a way that an incompatibility exists , programmer 14 or 44 , or programming interface 34 , provides a visual indication on the respective display to inform the user of the situation , and provides on - screen guidance as to how to correct the situation . in addition , when the user attempts to correct the programming error , systems 10 and 20 provide immediate feedback as to the success of the correction . a display which could be used to control systems 10 and 20 is shown in fig4 . the display in fig4 is geared toward the defibrillator system shown in fig3 but can be generalized to control of any medical device 12 or 32 . representative three zone configurations are shown in fig4 . in the embodiment shown in fig4 system 10 includes up to three tachyarrhythmia zones ( labeled as vt - 1 , vt , and vf ). in one such embodiment , such as is shown in fig4 each zone is identified on display 24 with its label 70 and its rate threshold 72 . in the embodiment shown in fig4 label 70 and its associated rate threshold 72 are displayed within a zone rate bar 74 . in addition , a detection summary for each zone is displayed within detection button 76 for that zone and a therapy summary for each zone is displayed within therapy button 78 for that zone . in one embodiment , the user accesses the detection parameters for a zone by selecting the respective detection button 76 and accesses the therapy parameters for a zone by selecting the respective therapy button 78 . if a zone &# 39 ; s detection button 76 has been selected , the initial and redetection parameters 88 are displayed for that zone . for example , fig4 illustrates the initial and redetection parameters associated with the vt - 1 zone , while fig5 illustrates the initial and redetection parameters associated with the vt zone . detection enhancement rhythm discrimination categories 90 ( see fig4 and 5 ) are displayed as well for those zones in which enhancements are available . in one embodiment , the user selects rate threshold value 72 in order to change the rate threshold for that zone . in the embodiment shown in fig4 and 5 , the number of zones tachyarrhythmia zones can be modified by selecting one of the number buttons beneath the “# zones ” label . in one embodiment , if parameter settings have changed but have not yet been programmed into the pulse generator , hatch marks (////) will appear in the summary area . when the values are programmed , the hatch marks disappear . in one embodiment , a subset of zone configuration information is displayed when the system summary and quick check screens are visible , which allows a shortcut to the detection and / or therapy parameters screens . ( only presently programmed values are displayed ; it does not display changed data that has not yet been programmed into the device nor hatch marks .) in one embodiment , the user selects a shortcut icon to navigate to the tachy parameters screen , which displays detailed information . if a shortcut icon appears dim , it indicates that a change to the number of zones has not been programmed ; thus a shortcut is not available to the parameter screens . a brady therapy summary 80 is also visible in fig4 and 5 . this area displays the normal and post - shock bradycardia modes and rates . additional bradycardia parameter settings may be viewed and changed by selecting the brady summary button when a shortcut icon is visible , or the brady parameters tool . depending on which toolbox screen is visible , this summary button may show just the rate / zone bar or may include additional information as is shown in fig4 and 5 . toolbox 82 displays various features depending on the chosen toolbox button . the features allow interaction with the pulse generator as well as a review of data in pulse generator memory . only one tool may be selected at a time . ( in one embodiment , the system summary tool is selected when the application is initially accessed . however , if an episode is in progress at initial interrogation , the ep test screen will be displayed .) in the embodiment shown in fig4 and 5 , windows contain information relevant to a particular function . they may include names of pulse generator parameters and functions , value boxes to accommodate value changes , buttons to open additional windows , and buttons to cancel changes or close the window . to remove the window from the display , select the button that initiates activity or select the close or cancel button . message windows are used to provide feedback during communication sessions . some require action as indicated in the window before continuing the session , while others simply relay information without requiring further action or show status of an activity . many message windows have a cancel or close button ; select the desired button to cancel the action being performed as explained in the message and / or close the window . in the embodiment shown in fig4 and 5 , ecg display 84 is always visible . ecg display 84 shows real - time surface ecg traces , as well as real - time electrograms ( egms ) and event markers , which are useful in ascertaining system performance . in one such embodiment , a 20 - second snapshot of the ecg trace , electrograms , and markers can be printed automatically ; when the cursor is positioned over the ecg display the cursor changes to a camera icon ; click the left trackball key to “ capture ” the trace . the printed trace shows 10 seconds before and 10 seconds after the moment of command . in one embodiment , annotated event markers identify certain intrinsic cardiac and device - related events , and provide information such as sensed / paced events , decision of detection criteria , and therapy delivery . the markers are displayed on ecg display 84 . in one embodiment , real - time electrograms can be transmitted from the pace / sense or shocking electrodes to evaluate lead system integrity such as lead fractures , insulation breaks , or dislodgments . the number of zones , the zones &# 39 ; rate thresholds , and values for detection , redetection , and detection enhancement parameters can be programmed from the zone configuration display in fig4 and 5 in the following manner . first , select tachy parameters button 86 from toolbox 82 to display the zone configuration area and the selected zone &# 39 ; s parameters . next , change the number of zones by selecting the desired number ( 1 , 2 , or 3 ) from the # zones column . the zone configuration will display the selected number of zones with hatch marks overlaying the new zones , which have not been programmed into the device yet . third , change the rate threshold using either select box 72 from zone / rate bar 74 or via the zone &# 39 ; s detection button 76 . next , change any of the desired initial or redetection parameters . in one embodiment , hatch marks overlay the zone &# 39 ; s detection button 76 until the changed parameters have been programmed into the pulse generator . note : as parameter values are changed , the information icon and / or stop sign icon may appear at the top of the main application screen to inform of potential parameter interactions . modify parameters as required to get around these objections . detection and display of parameter interaction will be further discussed below . magnifying - glass icon 94 can be used ro display feature parameters . in addition , a number of details are shown in fig4 and 5 . for instance , detection enhancement details for vt - 1 zone are shown in fig4 while detection enhancement details for vt zone are shown in fig5 . detection enhancement parameters can be more easily programmed by identifying the type of rhythm discrimination desired and associating the clinical rhythms with particular detection enhancements . in one embodiment , the types of clinical rhythms include : atrial tachyarrhythmia , sinus tachycardia , and polymorphic vt . see “ system and method for detection enhancement programming ,” filed herewith , for more information on detection enhancement programming through the use of clinical rhythms . when a rhythm discrimination is selected , preselected values are displayed for the parameters that are suitable for discriminating that rhythm . from a zone &# 39 ; s detection screen ( window 92 in fig6 and 7 ), detection parameters can be turned on by selecting the detection enhancements on or off value box , or by selecting the individual rhythm types . window 92 is closed when the parameters values are as desired . as noted above , systems 10 and 20 provide almost immediate feedback of parameters interactions and how to correct them . in one embodiment , once the user has attempted to program an incompatible setting , systems 10 and 20 display a written message that describes the problem to the user . the written description of the programming conflict describes why the programming change is not allowed , and what specific parameters need to be changed in order to correct the problem . if more than one option is available to correct the incompatibility , all choices are displayed . in one embodiment , systems 10 and 20 list each of the parameters in question that may need to be adjusted , and a status icon for each . in one such embodiment , the visual display of the interactive feedback includes the use of icons to signify the status of the programming change . if a red stop sign is displayed , the programming change violates a rule of programming , and thus needs to be corrected before the system will allow programming of the medical device . if a yellow warning sign is displayed , the programming change is allowable , but caution should be used as to the limitations that may occur when the device is programmed as such . on seeing a red stop sign or a yellow warning sign , the user has the opportunity to change one or more programming parameter values . if the user does so and a green check mark or exclamation point is displayed , the programming change has corrected the issue , and thus no further programming is necessary . one visual display which can be used to provide such feedback is shown in fig8 . the example in fig8 is based on the defibrillator example of fig3 but could be extended to other medical devices . in display 100 of fig8 feedback is provided to the user in the form of a warning 102 , an icon 104 and one or more parameters 106 . in addition , display 100 may include parameters 108 . warning 102 gives the reason why the suggested programming settings are not allowed . icon 104 designated the status of the suggested programming change ( in this scenario , icon 104 is a yellow warning icon as described above ). parameters 106 are the parameters in question while parameters 108 are the additional parameters which may need to be adjusted . finally , there is a present value 110 and a change box 112 for each parameter 106 and 108 . in one embodiment , changes to parameters 106 and 108 are displayed immediately , with a visual confirmation of the success or failure of the change in programming . an example of a successful change in programming is shown in fig9 . in fig9 a change to the post - shock brady max tracking rate ( from 140 ppm in fig8 to 120 ppm in fig9 ) results in an acceptable post - shock brady minimum dynamic vrp parameter 116 . as a result , a positive icon 114 is displayed next to parameter 116 . ( in this scenario , icon 114 is a green check icon as described above . other symbols of correctness could also be used .) note that the possible problem with normal brady minimum dynamic vrp parameter 106 remains uncorrected at this time . another example of parameter interaction is shown in fig1 . in fig1 , feedback is provided to the user in the form of a warning 102 , an icon 104 and one or more parameters 106 . in addition , display 100 may include parameters 108 . as in fig8 warning 102 gives the reason why the suggested programming settings are not allowed . icon 104 designated the status of the suggested programming change ( in this scenario , the first icon 104 is a red stop sign icon while the second icon 104 is a yellow warning icon ). parameters 106 are the parameters in question while parameters 108 are the additional parameters which may need to be adjusted . finally , there is a present value 110 and a change box 112 for each parameter 106 and 108 . in one embodiment , when a new parameter is entered in the change column of display 100 , it is immediately checked for interactions with other parameters . this may be done , for example , by a review of the set of rules discussed above . if the new value violates interactive limits within the application , a parameter interaction stop sign is displayed as discussed above . in one such embodiment , this icon can be selected to access a parameter interaction screen such as is displayed in fig8 - 10 . once the parameter interaction screen is accessed , the user can make changes directly from within the window . similarly , if the new value creates a situation where the value is not forbidden but more information should be presented to the clinician , the warning sign icon is displayed . in one such embodiment , this icon can be selected to access a parameter interaction screen such as is displayed in fig8 - 10 . changes to the affected parameter or parameters need not be made in order to proceed . physician discretion is , however , advised depending on the type of patient or on other circumstances relating to the device . one should be careful when writing the rules which detect and display parameter interactions . each warning should include a description of the present clinical situation , the present equation at issue and suggestions for resolving the issue . the rules and the warnings must be coordinated to present meaningful warnings for all combinations of parameter interactions . in contrast to previous devices , this method of handling parameter interaction provides a more intuitive approach coupled with the capability to provide the user immediate feedback on the choices they have made . this saves time for the user . in addition , by allowing the user to make all necessary changes from one screen , rather than having to navigate through multiple screens , ease of use is improved . although specific embodiments have been illustrated and described herein , it will be appreciated by those of ordinary skill in the art that any arrangement which is calculated to achieve the same purpose may be substituted for the specific embodiment shown . this application is intended to cover any adaptations or variations of the present invention . therefore , it is intended that this invention be limited only by the claims and the equivalents thereof .	0
referring to fig2 , a power amplifier of the present invention includes : a comparator 1 , a bridge circuit 2 , and a low - pass filter 3 . referring to fig2 , the comparator 1 receives a first analog signal , compares the first analog signal with a reference signal , and then exports a square wave signal . the first analog signal refers in particular to an audio signal in all the embodiments hereinafter . referring to fig2 and fig3 , the bridge circuit includes : an inverter 23 , a first mems switch 24 and a second mems switch 25 . the inverter 23 is connected to the output end of the comparator 1 . referring to fig2 and fig3 , the first mems switch 24 connected to the output end of the comparator 1 receives a first voltage signal , which is a high voltage hv in this embodiment . the first mems switch 24 is also connected to the input end of the low - pass filter 3 . specifically , the first mems switch 24 comprises a first electrode 241 and a second electrode 242 . the first electrode 241 comprises a first basal plate 2411 , a first insulating layer 2412 , a first conductor 2413 and a second conductor 2414 . the first basal plate 2411 receives a first control signal ( not shown in the figures ), which controls the polarity of the first basal plate 2411 . the first insulating layer 2412 is upon the first basal plate 2411 , and the first conductor 2413 and the second conductor 2414 are arranged upon the first insulating layer 2412 with some interval . the first conductor 2413 is connected to the high voltage hv , and the second conductor 2414 is connected to the input end of the low - pass filter 3 . the second electrode 242 is connected to the input end of the comparator 1 . to be specific , the second electrode 242 comprises a first connecting conductor 2421 , a second insulating layer 2422 , a second polar plate 2423 , the second polar plate 2423 is connected to the input end of the comparator 1 , and the first connecting conductor 2421 and the second polar plate 2423 are arranged upon the opposite surface of the second insulating layer 2422 . referring to fig3 , the input end of the inverter 23 is connected to the output end of the comparator 1 . the second mems switch 25 connected to the output end of the inverter 23 receives a second voltage signal , which is a ground signal , in this embodiment . the second mems switch 25 is also connected to the input end of the low - pass filter 3 . specifically , the second mems switch 25 comprises a third electrode 251 and a fourth electrode 252 . the third electrode 251 comprises a third conductor 2511 and a fourth conductor 2512 . the third conductor 2511 is connected to the second voltage signal , and the fourth conductor 2512 is connected to the input end of the low - pass filter 3 . the third electrode 251 further comprises a second basal plate 2513 and a third insulating layer 2514 . the third insulating layer 2514 is upon the second basal plate 2513 , and the third conductor 2511 and the fourth conductor 2512 are arranged upon the third insulating layer 2514 with some interval . the second basal plate 2513 receives a second control signal ( not shown in the figures ), which controls the polarity of the second basal plate 2513 . the fourth electrode 252 is connected to the output end of the inverter 23 . to be specific , the fourth electrode 252 comprises a second connecting conductor 2521 , a third polar plate 2322 and a fourth insulating layer 2523 . the third polar plate 2522 is connected to the output end of the inverter 23 . the second connecting conductor 2521 and the third polar plate 2522 are arranged upon the opposite surface of the fourth insulating layer 2523 . what is more , the first mems switch 24 and the second mems switch 25 both comprise a spring arm 26 . the spring arm 26 of the first mems switch 24 is set on the first electrode 241 and connected to the second electrode 242 , so the first electrode 241 and the second electrode 242 can shift away from or close to each other . the spring arm 26 of the second mems switch 25 is set on the third electrode 251 and connected to the fourth electrode 252 , so the third electrode 251 and the fourth electrode 252 can shift away from or close to each other . referring to fig3 , the working process of the power amplifier in this embodiment is as follows . ordinarily , the first analog signal ( an audio signal ) is a sine wave , and the reference signal 5 is a triangular wave , which is generated by a triangular wave generator . the comparator 1 compares the audio signal with the reference signal 5 , and then outputs a square wave signal . the square wave signal is composed of alternate a third voltage and a fourth voltage , and the third voltage is higher than the fourth voltage . that the polarity of the square wave signal is positive means the square wave signal is the third voltage , and that the polarity of the square wave signal is negative means the square wave signal is the fourth voltage . in this embodiment , the polarity of the first control signal put on the first basal plate 2411 of the first mems switch 24 and the polarity of the second control signal put on the second basal plate 2513 of the second mems switch 25 are the same , for example , the polarity is negative ( the first control signal and the second control signal both are the fourth voltage ). the comparator 1 compares the audio signal with the reference signal 5 , and then outputs a square wave signal . when the polarity of the square wave signal is positive , the polarity of the second polar plate 2423 is positive too . because the polarity of the second polar plate 2423 and the first basal plate 2411 are opposite to each other , static pull - in working on the second polar plate 2423 draws it near to the first conductor 2413 and the second conductor 2414 of the first electrode 241 , in this way , the first conductor 2413 , the second conductor 2414 , and the first connecting conductor 2421 will bring into contact with each other and be activated , whereby the high voltage hv can be transmitted into the low - pass filter 3 . moreover , the polarity of the square wave signal is changed to negative after running through the inverter 23 , as well as the polarity of the third polar plate 2522 . because the polarity of the third polar plate 2522 and the second basal plate 2513 are the same , the third polar plate 2522 will not move to the second basal plate 2513 , so the second connecting conductor 2521 , the third conductor 2511 and the fourth conductor 2512 will not be activated . when the polarity of the square wave signal is negative , the polarity of the second polar plate 2423 is negative too , that is to say , the polarity of the second polar plate 2423 and the first basal plate 2411 are the same , thereby they will repel each other , and the second basal plate 2513 will depart from the second polar plate 2423 . moreover , the polarity of the square wave signal is changed to positive after running through the inverter 23 , as well as the polarity of the third polar plate 2522 . because the polarity of the third polar plate 2522 and the second basal plate 2513 are opposite to each other , the third polar plate 2522 will move to the third conductor 2511 and the fourth conductor 2512 , in this way , the third conductor 2511 and the fourth conductor 2512 will be connected through the second connecting conductor 2521 , and the ground signal will be transmitted to the input end of the low - pass filter 3 . thereby , the input end of the low - pass filter 3 will receive alternate hv and ground signal because of the output of the comparator 1 . that is to say , the amplitude value of the square wave signal which is output by the comparator 1 is amplified to hv after running through the first mems switch 24 and the second mems switch 25 . the square wave signal will be changed to an amplified audio signal ( the second analog signal ), and then transmitted to the input end of the loudhailer 4 . in addition , when the first control signal put on the first basal plate 2411 of the first mems switch 24 and the second control signal put on the second basal plate 2513 of the second mems switch 25 is positive ( for example , they are the third voltage ), the system can get the same effect . simply the difference is as follows . when the square wave signal output by the comparator 1 is positive , the second mems switch 25 turns on , while the first mems switch 24 turns off . when the square wave signal output by the comparator 1 is negative , the first mems switch 24 turns on , while the second mems switch 25 turns off . some variations to this embodiment of the present invention are as follows . the first control signal is put on the first basal plate 2411 , the output end of the comparator 1 is connected to the second polar plate 2423 , the second control signal is put on the third polar plate 2522 , and the output end of the inverter 23 is connected to the second basal plate 2513 . or , the first control signal is put on the second polar plate 2423 , the output end of the comparator 1 is connected to the first basal plate 2411 , the second control signal is put on the second basal plate 2513 , and the output end of the inverter , 23 is connected to the third polar plate 2522 . or , the first control signal is put on the second polar plate 2423 , the output end of the comparator 1 is connected to the first basal plate 2411 , the second control signal is put on the third polar plate 2522 , and the output end of the inverter 23 is connected to the second basal plate 2513 . in this embodiment , when the polarity of the first control signal and the second control signal both are negative , while the output signal of the comparator is positive , the first mems switch 24 will be switched on and the second mems switch 25 will be switched off . however , if the output signal of the comparator is negative , the first mems switch 24 will be switched off and the second mems switch 25 will be switched on . therefore , the first mems switch 24 and the second mems switch 25 will just be switched on when the polarity of the square wave signal is opposite . in conclusion , the present invention substitutes the transistors with surface mems switches whose on - off are under the control of a comparator , the power consumption is reduced . what is more , mems switches , comparators and low - pass filters all can adopt cmos technology , that is to say , mems switches , comparators and low - pass filters can be overlapped , which can reduce the size of all components and the manufacture costs . referring to fig4 , it is structural sketch of the power amplifier according to the second embodiment of the present invention . in this embodiment , the power amplifier comprises : a comparator 1 , a bridge circuit 2 , and a low - pass filter 3 . the difference between this embodiment and the first embodiment is as follows : the structure of a first mems switch 34 and a second mems switch 35 in this embodiment is different from the structure of the first mems switch 24 and the second mems switch 25 in the first embodiment . the first mems switch 34 comprises a first electrode 341 and a second electrode 342 which are arranged opposite to each other . the first electrode 341 comprises a first polar plate 3411 which receives a first control signal , a first conductor 3412 which connects to a high voltage hv , and a second conductor 3413 which connects to the input end of the low - pass filter 3 . in this embodiment , the first electrode 341 further comprises a first basal plate 3414 and a first insulating layer 3415 . the first basal plate 3414 is a semiconductor substrate such as silicon substrate , and the first insulating layer 3415 is a silicon dioxide layer . the first insulating layer 3415 is formed on the first basal plate 3414 . the first polar plate 3411 , the first conductor 3412 and the second conductor 3413 are formed on the first insulating layer 3415 . in this embodiment , the second electrode 342 comprises a first connecting conductor 3421 , a second polar plate 3422 and a second insulating layer 3423 . the second polar plate 3422 connects to the output end of the comparator 1 . the second polar plate 3422 and the first connecting conductor 3421 are formed on the opposite surface of the second insulating layer 3423 . referring to fig4 , the second mems switch 35 in the second embodiment comprises a third electrode 351 and a fourth electrode 352 which are arranged opposite to each other . the third electrode 351 comprises a fourth polar plate 3511 which receives a second control signal , a third conductor 3512 which connects to the ground , and a fourth conductor 3513 which connects to the input end of the low - pass filter 3 . in this embodiment , the third electrode 351 further comprises a second basal plate 3514 and a third insulating layer 3515 . the second basal plate 3514 is a semiconductor substrate such as silicon substrate , and the third insulating layer 3515 is a silicon dioxide layer . the third insulating layer 3515 is formed on the second basal plate 3514 . the fourth polar plate 3511 , the third conductor 3512 and the fourth conductor 3513 are formed on the third insulating layer 3515 . in this embodiment , the fourth electrode 352 comprises a second connecting conductor 3521 , a third polar plate 3522 and a fourth insulating layer 3523 . the third polar plate 3522 connects to the output end of the inverter 3 . the third polar plate 3522 and the second connecting conductor 3521 are formed on the opposite surface of the fourth insulating layer 3523 . in this embodiment , the first mems switch 34 and the second mems switch 35 both comprises a spring arm 36 , and it makes that the fourth electrode 352 shifts away from or close to the third electrode 351 , or the second electrode 342 shifts away from or close to the first electrode 341 , possible . referring to fig4 , the working process of this embodiment and the first embodiment are similar to each other . it is illustrated briefly thereafter . when the first mems switch 34 and the second mems switch 35 works , the polarity of the first control signal put on the first polar plate 3411 and the polarity of the second control signal put on the fourth polar plate 3511 are the same . when the polarity of the output signal of the comparator 1 is opposite to the first polar plate 3411 , the polarity of the first polar plate 3411 is also opposite to the second polar plate 3422 . the static pull - in between the first polar plate 3411 and the second polar plate 3422 draws the first connecting conductor 3421 near to the first conductor 3412 and the second conductor 3413 , in this way , the high voltage hv connected to the first connecting conductor 3421 can be transmitted into the input end of the low - pass filter 3 . moreover , because of the inverter 23 , the polarity of the fourth polar plate 3511 and the third polar plate 3522 are the same , the fourth electrode 352 will not move to the third electrode 351 , so the second connecting conductor 3521 , the third conductor 3512 and the fourth conductor 3513 will not be activated , and the ground signal will not be transmitted to the input end of the low - pass filter 3 . similarly , when the polarity of the output signal of the comparator 1 and the first polar plate 3411 are the same , the second electrode 342 of the first mems switch 34 will not move to the first electrode 341 , then the high voltage hv will not be transmitted to the input end of the low - pass filter 3 . the second electrode 352 of the second mems switch 35 will move to the first electrode 351 because of static pull - in , whereby the third conductor 3512 and the fourth conductor 3513 will be connected through the second connecting conductor 3521 , and the ground signal gnd will be transmitted to the input end of the low - pass filter 3 . again and again , the input end of the low - pass filter 3 receives a square wave signal whose amplitude value is hv because of the output signal of the comparator 1 . in other words , the square wave signal output by the comparator 1 is amplified to a square wave signal whose amplitude value is hv after transmitting through the first mems switch 34 and the second mems switch 35 . next the amplified square wave signal is amplified and converted into an audio signal by the low - pass filter 3 , and then transmitted to the loudhailer 4 . likewise , some variations to this embodiment of the present invention are as follows . the first control signal is put on the first polar plate 3411 , the output end of the comparator 1 is connected to the second polar plate 3422 , the second control signal is put on the third polar plate 3522 , and the output end of the inverter 23 is connected to the fourth polar plate 3511 . or , the first control signal is put on the second polar plate 3422 , the output end of the comparator 1 is connected to the first polar plate 3411 , the second control signal is put on fourth polar plate 3511 , and the output end of the inverter 23 is connected to the third polar plate 3522 . or , the first control signal is put on the second polar plate 3422 , the output end of the comparator 1 is connected to the first polar plate 3411 , the second control signal is put on the third polar plate 3522 , and the output end of the inverter 23 is connected to the fourth polar plate 3511 . these variations have the same effect . it is understandable that the first mems switch 34 and the second mems switch 35 used in a power amplifier can reduce the power consumption and the percentage area of the devices . referring to fig5 , the present invention is not necessarily comprising an inverter . the difference between the power amplifier in this solution and the power amplifier shown in fig2 is that the bridge circuit has different structure . in this solution , the bridge circuit 2 comprises a first mems switch 24 and a second mems switch 25 . the first mems switch 24 is under the control of a first control signal , connected to the output end of a comparator 1 , a low - pass filter 3 , and a high voltage hv . the second mems switch 25 is under the control of a second control signal , connected to the output end of a comparator 1 , a low - pass filter 3 , and a ground signal gnu . the first mems switch 24 and the second mems switch 25 switch on alternately when the polarity of the first control signal or the second control signal is opposite to the polarity of the output signal of the comparator 1 , and output the high voltage hv or the ground signal gnd accordingly to the low - pass filter 3 . then the low - pass filter 3 converts the hv or gnd signal into an audio signal and transmits the audio signal to a loudhailer 4 . referring to fig6 , how the invention adopts mems switches realizing power amplifying without an inverter is illustrated hereafter . the first mems switch 24 and the second mems switch 25 still adopt the structure shown in fig3 , but the opposite of the first control signal and the second control signal are opposite to each other . the first control signal is put on the first basal plate 2411 of the first mems switch 24 . the second control signal is put on the second basal plate 2513 of the second mems switch 25 . the working principle is the same as the power amplifier with an inverter . likewise , some variations to this embodiment of the present invention are as follows . the first control signal is put on the first basal plate 2411 , the output end of the comparator 1 is connected to the second polar plate 2423 , the second control signal is put on the third polar plate 2522 , and the output end of the comparator 1 is connected to the second basal plate 2513 . or , the first control signal is put on the second polar plate 2423 , the output end of the comparator 1 is connected to the first basal plate 2411 , the second control signal is put on the second basal plate 2513 , and the output end of the comparator 1 is connected to the third polar plate 2522 . or , the first control signal is put on the second polar plate 2423 , the output end of the comparator 1 is connected to the first basal plate 2411 , the second control signal is put on the third polar plate 2522 , and the output end of the comparator 1 is connected to the second basal plate 2513 . the working process is similar to the first embodiment . referring to fig7 , how the invention adopts mems switches realizing power amplifying without an inverter is illustrated hereafter . the first mems switch 34 and the second mems switch 35 still adopt the structure shown in fig4 , but the polarity of the first control signal and the second control signal are opposite to each other . the first control signal is put on the first polar plate 3411 of the first mems switch 34 . the second control signal is put on the fourth polar plate 3511 of the second mems switch 35 . the working principle is the same as the power amplifier with an inverter . likewise , some variations to this embodiment of the present invention are as follows . the first control signal is put on the first polar plate 3411 , the output end of the comparator 1 is connected to the second polar plate 3422 , the second control signal is put on the third polar plate 3522 , and the output end of the comparator 1 is connected to the fourth polar plate 3511 . or , the first control signal is put on the second polar plate 3422 , the output end of the comparator 1 is connected to the first polar plate 3411 , the second control signal is put on the fourth polar plate 3511 , and the output end of the comparator 1 is connected to the third polar plate 3522 . or , the first control signal is put on the second polar plate 3422 , the output end of the comparator 1 is connected to the first polar plate 3411 , the second control signal is put on the third polar plate 3522 , and the output end of the comparator 1 is connected to the fourth polar plate 3511 . the working process is similar to the first embodiment . in addition , the mems switch can be formed with other types of structures , such as three - electrode mems switches . in this three - electrode scheme , the middle electrode is a movable part , and the polarity of the up electrode is opposite to the down electrode . if different voltages are put on the middle electrode , the up and down electrode will generate an attractive force and a repelling force , and perform switching on - off function by this means . in a word , this kind of switch also can achieve the purpose that using mems switches realize power amplifying . the detailed working principle is the same as adopting the first mems switch 24 and the second mems switch 25 . in the end , although the above descriptions take an audio signal as example , the present invention is also fit for other analog signals . although the present invention has been disclosed as above with reference to preferred embodiments thereof but will not be limited thereto . those skilled in the art can modify and vary the embodiments without departing from the spirit and scope of the present invention . accordingly , the scope of the present invention shall be defined in the appended claims .	7
in fig1 - 4 , an f type coupler head is shown generally at 10 . the knuckle side of the coupler is shown at 12 , and the guard arm side at 14 . as best seen in fig1 coupler front face 16 has a generally flat , vertical planar section . coupler face 16 includes throat portion 18 extending toward knuckle side 12 in a curved manner toward pivot lugs 20 having pin holes 22 . it is within pivot lugs 20 that a knuckle 24 is received and retained in a pivotal manner with a pin ( not shown ) that extends through pin holes 22 and a corresponding hole 26 in knuckle 24 . located behind pivot lugs 20 are buffing shoulders 28 which form a pocket for receiving knuckle 24 . projecting from buffing shoulders 28 are pulling lugs 30 behind which are engaged by ccrresponding pulling surfaces 32 of knuckle 24 . fig4 shows the prior art design profile of a bottom pulling lug 30 . it is to be understood that the design profile in top and bottom pulling lugs 30 are similar . pulling lug 30 includes a knuckle interface comprising a substantially vertical pulling surface 34 which extends into a radial fillet 36 having a constant radius . coupler head 10 also includes a second fillet 38 also of constant radius which forms the left - half portion of a raised boss 40 for a thrower hole 42 . thrower hole 42 receives a pivot portion of a thrower ( not shown ) which rotates around to throw open knuckle 24 during uncoupling . located between and separating radial fillet 36 from raised boss 40 is a substantially flat surface 44 . it is at the junction between radial fillet 36 and flat surface 44 where fatigue cracks have been found to form . fig5 shows a bottom pulling lug 46 embodying the improved design of the present invention . the radial fillet of constant radius has been replaced with a parabolic fillet 48 having a variable radius that increases with the distance away from an unchanged substantially vertical surface 50 . in addition , substantially flat surface 44 which was located between radial fillet 36 and raised boss 40 in the prior art design profile of fig4 has been eliminated . in the improved design , parabolic fillet 48 extends into a second fillet 52 of constant radius at a raised boss 54 for thrower hole 56 , said boss 54 and thrower hole 56 being unchanged over the prior art design profile . the prior art design profile is shown in dashed lines in fig5 to illustrate the modifications in said improved design profile . the substitution of parabolic fillet 48 and the resulting elimination of substantially flat surface 44 from the prior art design profile greatly reduces the stress concentration between substantially vertical surface 50 and raised boss 54 by distributing the load over a larger , smoother curved surface area , namely along the entire parabolic curve 48 , instead of the mere radial fillet 36 of the prior art design profile . this reduction in stress concentration reduces the likelihood of fatigue cracks forming behind the pulling lugs . a parabolic fillet is preferred due to the small space envelope which is available along the x and y axes as shown in fig5 . the distance along the y axis remains unchanged over the prior art pulling lug design because the fillet may not extend any higher into substantially vertical surface 50 which interfaces with a corresponding pulling surface on a knuckle . such an extension of the fillet would result in the loss of interchangeability with knuckles of standard design . the distance along the x axis is greater in the improved design , however , as the parabolic fillet 48 eliminates substantially flat surface 44 of the prior art design profile of fig4 . to construct an approximate parabolic fillet 48 profile , the distances along the x and y axes may be divided into the same number of segments and identically numbered from top to bottom and from left to right as shown in fig6 . points having the same number are then connected by straight lines resulting in an envelope of gradually increasing radius which approximates a parabolic curve . the parabolic fillet can also be constructed using the parabolic equation y 2 = 2fx with the origin of the parabola located at point 58 where the substantially vertical surface 50 meets the fillet 48 as shown in fig5 . the constant f in the parabolic equation is selected in accordance with the x and y space limits for the given pulling lug . while a parabolic fillet is preferred , other compound curves of variable radii such as ellipses or catanaries would also reduce the stress concentration . furthermore , while an f type coupler head is shown in the drawings , identical modifications could be made to the pulling lugs of an e type coupler to achieve the same result . the foregoing description and drawings explain and illustrate the best known mode of the invention and those skilled in the art who have the disclosure before them will be able to make modifications and variations therein without departing from the scope of the invention which is defined in the following claims .	1
fig1 a - 1c show a process for fabricating an embodiment of a channel region 100 of a transistor 10 . in fig1 a , channel region 100 is implanted with a dopant selected to provide a relatively low threshold voltage for transistor 10 . in fig1 b , a photoresist mask 102 is formed over channel region 100 to establish a first portion 120 and leave a second portion 122 exposed . the second portion 122 of channel region 100 is implanted with a dopant selected to provide a relatively high threshold voltage . in fig1 c , a finished channel region 100 is shown with first portion 120 and second portion 122 . the remainder of transistor 10 to include a gate region 104 , a source region 106 , and a drain region 108 can be formed in a conventional manner . fig2 a - 2c show an alternative process for fabricating an embodiment of channel region 100 of transistor 10 . in fig2 a , channel region 100 is implanted with a first dopant selected to provide a relatively low threshold voltage for transistor 10 . in fig2 b , a gate region 104 is formed over channel region 100 . a photoresist mask 102 is formed over channel region 100 and gate region 104 to establish a first portion 120 and leave a second portion 122 exposed . the second portion 122 of channel region 100 is implanted with a second dopant selected to provide a relatively high threshold voltage . the implanting of the second dopant may be performed at an angle relative to transistor 10 to assist in establishing second portion 122 and first portion 120 . in fig2 c , a finished channel region 100 is shown with first portion 120 and second portion 122 . the remainder of transistor 10 to include gate region 104 , source region 106 , and drain region 106 can be formed in a conventional manner . in one embodiment , second portion 122 is shown in closer proximity to source region 106 of transistor 10 than first portion 120 . though shown in this manner , transistor 10 can also be fabricated with second portion 122 being in closer proximity to drain region 108 than first portion 120 . fig3 shows a schematic circuit diagram of transistor 10 . by establishing first portion 120 and second portion 122 within channel region 100 , transistor 10 logically becomes a dual transistor device with a lower threshold voltage transistor 112 serially connected with a higher threshold voltage transistor 114 . the total length of channel region 100 is similar to channel lengths of conventional transistors . higher threshold voltage transistor 114 has a channel length of α × l , where l is the total channel length of channel region 100 and a is a fraction less than one . lower threshold voltage transistor 112 has a channel length of l −( α × l ). by optimizing a to be a small fraction ( such as approximately 0 . 1 to 0 . 15 ), the on current can mainly be determined by lower threshold voltage transistor 112 having a longer channel length and the off current can mainly be determined by higher threshold voltage transistor 114 having the shorter channel length . higher threshold voltage transistor 114 reduces leakage current exponentially as the threshold voltage is increased . however , this has a minimal affect on the on current of transistor 10 because the on current is a quadrature or linear function of threshold voltage as well as from higher threshold transistor 114 having a smaller channel length . the increase resistance provided by higher threshold transistor 114 enables the threshold voltage of lower threshold transistor 112 to become even lower and still maintain a lower off current than a traditional transistor design with a uniform channel region . thereby , the on current can be further increased . in addition , the off leakage current from lower threshold voltage transistor 112 is essentially blocked by higher threshold voltage transistor 114 . in essence , higher threshold voltage transistor 114 acts somewhat as an insulator in the off state to absorb the leakage current flowing through lower threshold voltage transistor 112 . if maintaining low leakage current is of primary interest , then a can be larger ( e . g ., greater than 0 . 5 ). fig4 shows an alternate embodiment of channel region 100 of transistor 10 . though shown in fig3 as having higher threshold voltage transistor 114 in series with lower threshold voltage transistor 112 , channel region 100 may be implanted in a manner to provide any number of transistors within physical transistor 10 . for example , channel region 100 may have a first portion 220 , a second portion 222 , and a third portion 224 . second portion 222 may establish a lower threshold voltage transistor 212 . first portion 220 and third portion 224 may establish higher threshold transistors 214 and 216 . first portion 220 and third portion 224 may be of equal or different lengths . similarly , second portion 222 may establish a higher threshold voltage transistor 212 . first portion 220 and third portion 224 may establish lower threshold transistors 214 and 216 . in essence , this is an extension of the configuration discussed above with reference to fig1 a - 1c and 2 a - 2 c , where second portion 122 can be formed to separate first portion 120 into two sub - portions with each sub - portion having a similar doping profile or further processed to have different doping profiles . further , second portion 122 may be positioned such that each sub - portion may have similar or different lengths . fig5 shows an alternative embodiment of channel region 100 of transistor 10 . in this embodiment , second portion 122 has a lesser depth than first portion 120 . second portion 122 may be implanted to provide a relatively higher threshold voltage . second portion 122 may also be formed to include a relatively same number of dopants as it would have if it were fabricated with the same depth as first portion 120 . the amount of dopant in second portion 122 is merely confined to a smaller area , resulting in higher dopant concentration . this provides an advantage when the drain voltage of second portion 122 becomes higher . without this embodiment , the higher drain voltage will cause more dibl ( drain induced barrier lowering ) and clm ( channel length modulation ) effects . by selecting dopants to establish different threshold voltages in transistor 10 , the on current for transistor 10 can be increased without causing a corresponding increase in the off leakage current of transistor 10 . in one example embodiment having a 100 nm length for second portion 122 and an 800 nm length for first portion 120 providing a 900 nm length for channel region 100 , second portion 122 can provide a 150 mv higher threshold voltage and first portion 120 can provide a 150 mv lower threshold voltage than a single dopant implanted channel region . the off leakage current may be reduced by a factor of five with a corresponding 35 % increase in on current . moreover , this technique can be applicable for any type of transistor , including junction field effect and metal oxide semiconductor field effect transistor designs . thus , it is apparent that there has been provided , in accordance with the present invention , a transistor with dual threshold voltages and method of fabrication thereof that satisfies the advantages set forth above . although the present invention has been described in detail , various changes , substitutions , and alterations may be readily ascertainable by those skilled in the art and may be made herein without departing from the spirit and scope of the present invention as set out in the appended claims . moreover , the present invention is not intended to be limited in any way by any statement made herein that is not otherwise reflected in the following claims .	7
the present invention provides an alternative approach to improving transfection reagents . the compositions and methods of the present invention were shown to be unusually effective . in preferred embodiments , the present invention provides the combination of two or more cationic lipoids to provide improved transfection reagents . in some embodiments , the first cationic lipoid is a standard cationic lipoid used in transfection reagents and the second cationic lipoid is of the nature where , when combined with the first cationic lipoid in transfection reagents , alters the hydrophobicity of the hydrophobic mass either in the extent of hydrophobicity of the lipoids or in the organization of the lipoids compared to the reagents in the absence of the second cationic lipoid , and wherein such change in hydrophobicity increases the ability of the transfection reagents to transfect cells . in some embodiments , the second cationic lipoid is a lipoid that has higher water solubility than the first lipoid and / or that increases the exposure of the hydrophobic core of the lipoid structure to an aqueous environment ( e . g ., disrupt the bilayer of a liposome ) as compared to the same structure in the absence of the second cationic lipoid . the degree of increase in water solubility and / or increased exposure of the hydrophobic core that finds use in the present invention can readily be measured by detecting transfection efficiency with and without the second cationic lipoid or by comparing the transfection reagents having the second cationic lipoid to other transfection reagents ( see e . g ., example 1 for such a method ). optimization to increase water solubility and / or increased exposure of the hydrophobic core can be achieved by a variety a methods . for example , in some embodiments , the second cationic lipoid has a smaller hydrophobic mass ( e . g ., shorter hydrophobic tail ). in some embodiments , the second cationic lipoid is functionalized to add hydrophilicity ( e . g ., canceling some of the hydrophobic mass ). in some embodiments , the functionalization comprises addition of one or more polar groups . in some embodiments , a polar fluorophore is added ( e . g ., nbd ), providing the added feature of fluorescent detectability . for example , particularly efficient transfection reagents were produced by the combination of dilauroyl ( 12 carbon chain ) and dioleoyl ( 18 carbon chain ) homologues of o - ethylphosphatidylcholine . this mixture transfected dna into human umbilical artery endothelial cells ( huaecs ) more than 30 - fold more efficiently than either compound separately . a unique advantage of this kind of combination agent is that transfection can be optimized either in the presence or absence of serum by adjusting the component ratio . in some embodiments , the second lipoid has chains that are not significantly different in length from those of the first lipoid , but the second lipoid has chains that have a larger cross - sectional area . in some embodiments , the second lipoid has chains that are differently shaped from those of the first lipoid , so as to occupy space in the bilayer in a different way than those of the first lipoid . cationic lipids have been widely used for the delivery of plasmid and antisense dna into eukaryotic cells ; however , inefficiency of transfection is a major problem confronting their use in gene therapy . vascular endothelial cells act as an interface between circulating blood and various tissues and organs of the body , and are known to be involved in inflammatory processes such as leukocyte recruitment , cytokine production ( see , e . g ., koning g a , et al ., endothelium 2002 , 9 : 161 - 171 ; neuhaus t et al ., clinical science 2000 ; 98 : 461 - 470 ; stier s et al ., febs letters 2000 ; 467 : 299 - 304 ; each herein incorporated by reference in their entireties ), and to play a major role in the pathogenesis of atherosclerosis ( see , e . g ., behrendt d , and ganz p ., am j cardiol 2002 ; 90 : 40l - 48l ; ulrich - merzenich g , et al ., european journal of nutrition 2002 ; 41 : 27 - 34 ; each herein incorporated by reference in their entireties ), as well as angiogenesis ( see , e . g ., ellis l m . am surg 2003 ; 69 : 3 - 10 ; nam n h , parang k . curr drug targets 2003 ; 4 : 159 - 179 ; ranieri g , and gasparini g ., curr drug targets immune endocr metabol disord 2001 ; 1 : 241 - 253 ; sylven c . drugs today ( barc ) 2002 ; 38 : 819 - 827 ; each herein incorporated by reference in their entireties ), on which the growth and spread of tumors are dependent . hence , they are of considerable interest as a gene therapy target ( see , e . g ., baker ah ., j card surg 2002 ; 17 : 543 - 548 ; morishita r ., circ j 2002 ; 66 : 1077 - 1086 ; each herein incorporated by reference in their entireties ). even though they are readily accessible , gene therapy with nonviral vectors of endothelial tissue has been seriously hampered by the fact that endothelial cells are very difficult to transfect . according to struck et al ., biochemistry 1981 , 20 : 4093 - 4099 , the transfection efficiency of vascular endothelial cells with cationic lipids was only 2 %. it is known that the cytotoxicity of cationic lipids increases with the shortening of acyl groups and so cationic lipids used in transfection invariably have alkyl chains that are 14 or more carbon long . the present invention provides solutions to such problems . for example , in one embodiment , a short chain cationic phosphocholine ( 1 , 2 - dilauroyl - sn - glycero - 3 - ethylphosphocholine , edlpc ), when combined with longer chain compounds ( 1 , 2 - dioleoyl - sn - glycero - 3 - ethylphosphocholine , edopc , or 1 , 2 - dimyristol - sn - glycero - 3 - ethylphosphocholine , edmpc ) dramatically enhances ( up to 30 - fold ) the transfection efficiency of human umbilical artery endothelial cells ( huaecs ) even though , individually , edlpc , edopc or edmpc are quite weak transfection reagents . moreover , transfection efficiency can be adjusted to be optimal either in the presence or absence of serum by changing the edlpc / edopc ratio and the ratio of total lipids to dna . under optimal conditions , transfection efficiency can be achieved up to 15 % both in the presence and absence of serum . thus , these formulations constitute a novel form of cellular transfection reagent and offer entirely new formulations for optimizing in vivo gene delivery . at present , only phosphatidylethanolamine and cholesterol are used as the helper lipids to improve the transfection properties of cationic lipids . unlike these prior methods ( although they may be used in conjunction with the present invention ), the present invention employs compounds with different hydrophobicity - hydrophilicity balance to improve the gene delivery properties of lipoplexes . the properties of lipoplexes can be tuned by changing the ratio of the different lipoids ( e . g ., the ratio of medium chain to long chain cationic lipoids and the ratio of lipoid to dna ). in some preferred embodiments , one or more agents may be added to the cationic lipoid mixtures so as to further increase transfection efficiency . examples of agents include , but are not limited to , cholesterol , polyamidoamine dendrons , histidylated lipids , octylglucoside , phycoerythrin , and non - cationic lipids . in some preferred embodiments , the cationic lipoid mixtures may be transfected with additional transfection reagent systems so as to further increase transfection efficiency . examples of transfection reagent systems include , but are not limited to , lipofectamine ( invitrogen ), optifect ( invitrogen ), 293fectin ( invitrogen ), oligofectamine ( invitrogen ), cellfectin ( invitrogen ), lipofectin ( invitrogen ), dmrie - c ( invitrogen ), exgen 500 ( euromedex ), octylglucoside , fugene ( roche ), effectgene ( qiagen ), and superfect ( qiagen ). in some embodiments , the first or second lipoids are not cationic but are configured to have a structural impact on the bilayer into which they are incorporated ( e . g ., to impact the water solubility than a cationic lipoid used alone , to increase the exposure of the hydrophobic core of the lipoid structure to an acqueous environment , or to disrupt the packing of the bilayer of a liposome or other structure as compared to the same structure in the absence of a second cationic lipoid ). the transfection system described herein is useful to express any polypeptide of interest or to transfect any nucleic acid of interest ( e . g ., sirnas , antisense oligonucleotides , expression vectors , etc .). the transgene will generally encode a native or recombinant protein , although the expression of other polypeptides , such as epitopes or other immunologically active polypeptides , are contemplated within the scope of this invention . examples of proteins that can be expressed using the method of the present invention are hormones ; cytokines , such as growth factors ; enzymes ; receptors ; oncogenes ; polypeptide vaccines , viral proteins , and structural and secretory proteins . the transgene employed in the constructs of the invention can be cloned sequences that retain intronic regions . if the exonic structure of the gene is known , the coding exons can be inserted in the constructs . expression of the polypeptide of interest can be directed by a promoter homologous to the polypeptide coding sequences ( for example , human glucose - 6 - phosphate dehydrogenase under the control of its own transcription promoter sequences ). further , other homologous or heterologous expression control elements ( e . g ., affecting transcription , translation , or post - translational events ) may be used . it should be understood that expression of the transgene in the mammalian cells of the invention can be stable or transient . even transient expression , at a higher than normal level , is useful for functional studies in the cells or for the production and recovery of proteins of interest . in addition to selectable markers and transgenes , the constructs described herein may contain suitable regulatory elements . regulatory elements ( or control elements ) are selected for use in the host cell of interest ; for example , selectable markers may be included to allow propagation in microorganisms , ( e . g ., f1 origin of replication and ampicillin resistance encoding sequences ). such regulatory elements include , but are not limited to , transcription promoters , transcription enhancer elements , transcription termination signals , polyadenylation sequences ( located 3 ′ to the translation stop codon ), sequences for optimization of initiation of translation ( located 5 ′ to the coding sequence ), translation termination sequences , secretion signal sequences , and sequences that direct post - translational modification ( e . g ., glycosylation sites ). transcription promoters can include inducible promoters ( where expression of a polynucleotide sequence operably linked to the promoter is induced by an analyte , cofactor , regulatory protein , etc . ), repressible promoters ( where expression of a polynucleotide sequence operably linked to the promoter is induced by an analyte , cofactor , regulatory protein , etc . ), and constitutive promoters . the cells ( e . g ., host cells ) employed in this invention include all eukaryotic cells including mammalian cells ( in vivo or in vitro ), cell lines , and cell cultures . the cells can be derived from mammals , such as mice , rats , or other rodents , or from primates , such as humans or monkeys . mammalian germ cells or somatic cells can be employed for this purpose . it will be understood that primary cell cultures or immortalized cells can be employed in carrying out the techniques of the present invention . the cells may also reside in vivo . examples of cells used in the present invention include , but are not limited to , huaaec cells , human dermal fibroblast cells , cancer cells ( e . g ., myeloma cells ). the transformed cells obtained by some embodiments of the present invention can be employed for the preparation of continuous cell lines in which the cells are essentially immortal , or for the preparation of established cell lines that have the potential to be subcultured in vitro . continuous cell lines and established cell lines can be obtained from a variety of organisms and organs , such as rodent embryos ; primate kidneys ; rodent and human tumors ; and fibroblast , epithelial , or lymphoid cells . cells exhibiting the highest levels of expression can be cloned , if desired . the following examples are provided to demonstrate and further illustrate certain preferred embodiments of the present invention and are not to be construed as limiting the scope thereof . experiments conducted during the development of the present invention found that attention to the hydrophobic portions of medium and long - chain cationic lipids synergistically enhance transfection . it was found that a combination of two cationic lipid derivatives with the same head group but tails of different chain lengths behave considerably differently as transfection agents than the separate molecules . for example , the combination of the dilauroyl ( 12 carbon chain ) and the dioleoyl ( 18 carbon chain ) homologues of o - ethylphosphatidylcholine transfected dna into primary human umbilical artery endothelial cells ( huaecs ) more than 30 - fold more efficiently than either compound separately . the present invention is not limited to a particular mechanism . indeed , an understanding of the mechanism is not necessary to practice the present invention . nonetheless , these results suggest that the hydrophobic portions of medium and long - chain cationic lipids is far more important than previously assumed . an advantage of this kind of combination agent is that transfection is optimized either in the presence or absence of serum by adjusting the component ratio . considering that there are more opportunities to modify and combine the hydrophobic moieties on cationic lipoids than there are for variation of the head groups , a study of the transfection efficiency of lipids with different kinds of tails and different kinds of combinations of those tails leads to new and improved nonviral vectors was conducted . a unique advantage of the cationic phospholipoids for hydrophobic structure modification is that they allow use of specific enzymes in their synthesis , a feature not exhibited by the other cationic lipoids described in the literature because those compounds are not based on a natural product . fig1 shows that combining edlpc with edopc enhances by ˜ 30 - fold of the extent of transfection of huaecs , compared to edlpc or edopc alone . the ratio of edlpc to edopc affected performance , with different ratios optimal , depending upon whether serum is present or absent . the edlpc / edmpc mixture exhibits the similar pattern to that of edlpc / edopc , but the extent of transfection is lower than that of edlpc / edopc . on the basis of the results presented above , edlpc / edopc ( 80 / 20 ) and edlpc / edopc ( 60 / 40 ) were chosen to further optimize transfection ; the ratio of lipids to dna and the amount of dna were used as optimization parameters . fig2 depicts the change of transfection with the ratio of edlpc to edopc and the ratio of total lipids to dna . for some formulations , transfection without serum was better than that in serum ; but for others , transfection in serum was better than that in the absence of serum . the highest transfection in the absence of serum was obtained when edlpc / edopc = 80 / 20 and lipid / dna = 4 / 1 , with 0 . 5 μg dna / well ; under these conditions the extent of expression was 8 × higher than that in the presence of serum . in contrast , the most efficient transfection in the presence of serum was when edlpc / edopc = 60 / 40 and lipid / dna = 6 / 1 , with 1 . 0 μg dna / well , under which condition the expression was 20 × that in the absence of serum . according to x - gal staining , 15 % of the cells treated under both of these conditions were positive . this efficiency of transfection is more than an order of magnitude higher than has been previously reported for transfection of these primary cells . these two formulations were thus used in the subsequent studies . such assays can be used to readily determine optimal ratios and optimal components of the transfection reagents of the present invention . the cell viability and the percentage of cells transfected for the two formulations were determined using the mtt method and x - gal staining , respectively ( table 1 ). those data revealed that the low transfection efficiency in the absence of serum for edlpc / edopc = 60 / 40 and lipid / dna = 6 / 1 was due to high cytotoxicity . while the present invention is not limited to any particular mechanism of action and an understanding of the mechanism of action is not necessary to practice the present invention , it is contemplated that the medium chain lipid facilitates mixing of the lipoplex lipid with cellular lipid , which could lead to the neutralizing of the positive charge of the cationic lipid and facilitate release of dna from the complex . under such circumstances , edlpc could facilitate fusion ( or at least lipid mixing ) of cationic liposomes with anionic liposomes . the fusion of edlpc / edopc ( 80 / 20 ), edlpc / edopc ( 60 / 40 ) and pure edopc lipoplexes were compared to phosphatidylglycerol - containing ( anionic ) liposomes . membrane fusion was measured using a fret assay ( see , e . g ., struck d k , et al ., biochemistry 1981 ; 20 : 4093 - 4099 ; herein incorporated by reference in its entirety ) that measures reduction of energy transfer between nbd - pe and rh - pe in cationic lipids of the lipoplexes as they fuse with egg - pc liposomes containing 20 % dopg . from fig3 , it is seen that the extent of fusion of edlpc / edopc ( 80 / 20 ) and edlpc / edopc ( 60 / 40 ) lipoplexes is significantly higher than that of pure edopc . the present invention is not limited to a particular mechanism . indeed , an understanding of the mechanism is not necessary to practice the present invention . nonetheless , these results indicate that increased transfection efficiency is associated with membrane fusion characteristics . in order to determine if this pattern of fusion is also observed within cells ( e . g ., the mixture is more prone to fuse with endosomal membranes facilitating escape of dna from endosomal degradation and nuclei entrance ) the intracellular distribution of fluorescent lipid and oligonucleotide in edopc and edlpc / edopc ( 60 / 40 ) lipoplexes was investigated . it was found that both lipid and oligonucleotide in edopc lipoplexes remained in the cytoplasm for at least 20 hours , whereas a large amount of the oligonucleotide from edlpc / edopc ( 60 / 40 ) lipoplexes entered the nuclei , in particular at the early time point of 2 h , although lipid in edlpc / edopc ( 60 / 40 ) lipoplexes remained in the cytoplasm at this and all other time points . fig4 shows oligonucleotide distribution of edopc and edlpc / edopc / dna ( 60 / 40 / 16 . 7 ) lipoplexes in huaecss . lipoplexes were labeled with a fluorescein derivative of a double - stranded dodecameric oligonucleotide . cells were incubated with the resulting lipoplexes in the presence of serum for 2 h and imaged under a fluorescence microscope after being washed in hbss . as shown in fig4 , the results of these experiments indicated that in the presense of the lipoid mixture there was an increase in the nuclear distribution of highly fluorescent oligonucleotides . similar images were obtained with fluorescent plasmid dna , although the fluorescence of the nucleus was less intense . escape of lipoplexes from endosomes prior to their entry into lysosomes is important for transgene efficient expression . it is contemplated that fusion of lipoplexes with endosomal membranes facilitates dna release from endosomes into cytoplasm , and thus increase dna expression . while the present invention is not limited to any particular mechanism of action and an understanding of the mechanism of action is not necessary to practice the present invention , it is contemplated that this may be one reason that transfection by the mixtures of lipid is much higher than that of pure edopc . the present invention is not limited to a particular mechanism . indeed , an understanding of the mechanism is not necessary to practice the present invention . nonetheless , it is contemplated that dissociation of dna from the surface of a lipoid is caused by neutralization of the lipoid by cellular anionic lipids . such neutralization implies fusion or transfer of lipids as a necessary prerequisite of efficient transfection , and implies that the dna must become sufficiently free of the lipid - lipoid array to be transcribed in the nucleus . unlike normal cellular lipids , the combination of cationic lipoids and anionic lipids gives rise to a variety of non - lamellar phases which may or may not be capable of retaining a molecule as large as a typical plasmid . generally , generation of lipid phases through combination of cationic and anionic lipids is dependent upon lipids ( see , e . g ., tarahovsky , y . s ., et al ., 2004 , biophysical journal 87 : 1054 - 1064 ; herein incorporated by reference in its entirety ). for example , mixtures such as edopc - edlpc , when reconstituted with anionic lipids such as phosphatidylglycerol , give rise to a highly curved inverted micellar cubic phase . this phase is characterized by a cubic array of balls ( shells ) in which amphipathic molecules are organized with their polar portion facing a small aqueous core and their hydrophobic tails facing those of other shells . these phases have aqueous spaces too small to entrap either a plasmid or other dna molecule . separate experiments have revealed that treatment of edopc - edlpc lipoplexes with the anionic lipid , phosphatidylserine , releases more dna by far that does treatment of edopc lipoplexes with phoshatidylserine . the present invention is not limited to a particular mechanism . indeed , an understanding of the mechanism is not necessary to practice the present invention . nonetheless , it is contemplated that there are at least two important effects involved when certain kinds of lipoid mixtures are used to prepare lipoplexes . first , the mixed lipoid lipoplex may acquire anionic lipid from the cell ( e . g ., perhaps by membrane fusion or molecular exchange ) faster and / or to a larger extent than do lipoplexes composed of lipoids of a single type . second , the phase or 3 - dimensional array assumed after the cellular anionic lipid and the lipoplex lipoid may have such a structure as to release faster and / or to a greater extent its cargo of dna than do conventional lipoplexes . serum strongly influences properties of lipoplexes , so experiments were conducted to examine the effect of serum on the composition of these two formulations . in fig5 , one sees that during 90 min incubation in serum , for edlpc / edopc = 60 / 40 , 20 % of the edopc and 10 % of the edlpc were extracted from the lipoplexes ; in the case of edlpc / edopc = 80 / 20 , 30 % of the edopc and 50 % of the edlpc are extracted . furthermore , at early times ( 30 min ), which are contemplated to be more important for endocytosis , the extraction of edlpc and edopc from edlpc / edopc = 80 / 20 was much larger than that from edlpc / edopc = 60 / 40 . gene expression in delipidated serum was tested ( fig6 ). transgene expression of both two formulations decreased significantly in delipidated serum , in which ˜ 80 % lipids ( including cholesterol , hdl cholesterol , ldl cholesterol and phospholipids ) are absent relative to normal serum . while the present invention is not limited to any particular mechanism of action and an understanding of the mechanism of action is not necessary to practice the present invention , it is contemplated that this indirectly confirms serum extraction of lipids , since delipidated serum , with a higher lipid binding capacity than normal serum , would also extract more lipids from the lipoplex . human dermal fibroblasts are another medically important cell type through participation in wound healing . it was contemplated that human dermal fibroblasts would be useful in gene therapy to accelerate wound healing . it was therefore of interest to determine if the “ mixed lipid ” effect also operates in these primary cells . it was found that the “ mixed lipid ” effect is more pronounced than with huaecs . the response in serum was not as pronounced , but efforts were not made to optimize the conditions for this system . a human multiple myeloma cell line that is extremely difficult to transfect was also investigated and the “ mixing effect ” was observed , although the transfection efficiency was very low ( 1 - 2 %). the mixed lipoid effect is not limited to cationic phospholipoids . as shown in fig7 , the effect is seen when a dimethylammonium with two c14 chains is mixed with edopc and when the c 18 phospholipoid is replaced with a dimethylammonium having two c 18 chains . the tap compounds , dotap and dmtap in various combinations , were investigated with each other and with edopc . in all cases substantial increases at intermediate compositions was observed . the present invention is not limited to a particular mechanism . indeed , an understanding of the mechanism is not necessary to practice the present invention . nonetheless , the mixed lipoid effect appears quite general , as would be anticipated if some aspect of the hydrophobicity of the lipoplex needs to be matched to the cell and the transfection conditions . although other lipoids can be synthesized to have chain length differences , it is unlikely that any other such compounds offer the flexibility of structural variation as the cationic phospholipoids . thus , while the present invention is not limited to the use of cationic lipoids , cationic lipoids are a preferred material . these compounds offer enormous flexibility in constructing molecules with varied amount and configuration of hydrophobic moieties . transfection of human dermal fibroblasts with edopc / epopc and edopc / ediphytanoyl pc transfection reagents fig8 shows that combining edopc with epopc ( one oleoyl chain , which is 18c &# 39 ; s with one double bond , and one palmitoyl chain , which is 16c &# 39 ; s without any double bond ) shows little mixing effect in transfection of human dermal fibroblast cells in the absence of serum . fig9 shows that combining edopc with ediphytanoyl pc ( two phytanoyl chains , 16 carbon chains with 4 methyl branches ) shows marked mixing effect in the transfection of human dermal fibroblast cells in the absence of serum . fig1 shows the results of transfecting huaecs with edopc / epopc , edopc / ediphytanoylpc , edopc / sdopc ( dopc with an 18 carbon chain instead of an ethyl group on the phosphate oxygen ), and edopc / ec18c10pc mixtures . new cationic phospholipids ( derivatives of phosphatidylcholine ) are contemplated including , but not limited to , medium chain cationic pc &# 39 ; s with phosphate oxygen alkyl substituents ranging in length from 2 to 24 c &# 39 ; s ); lyso cationic pc &# 39 ; s with one long chain ( c24 ) and a phosphate oxygen alkyl substituent with 2 to 12 c &# 39 ; s ; cationic pc &# 39 ; s with acyl groups having very much different chain lengths ; tetra - acyl cationic pc &# 39 ; s with short acyl chains ; and lipoids with very long (& gt ; 18 carbons ) acyl chains . in some cases , acyl or alky substituents may be branched so as to effectively increase the number of chains without increasing the number of attachment points to the hydrophilic cationic head group . all publications and patents mentioned are herein incorporated by reference . various modifications and variations of the described method and system 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 preferred 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 that are obvious to those skilled in the relevant fields are intended to be within the scope of the following claims .	2
a detailed description of embodiments of the present invention is presented below . while the disclosure will be described in connection with these drawings , there is no intent to limit it to the embodiment or embodiments disclosed herein . on the contrary , the intent is to cover all alternatives , modifications and equivalents included within the spirit and scope of the disclosure as defined by the appended claims . fig2 illustrates an embodiment of one of the wireless devices / stations shown in fig1 . it can be configured to receive and process messages as disclosed below . generally speaking , station 120 can comprise any one of a wide variety of wireless computing devices , such as a desktop computer , portable computer , dedicated server computer , multiprocessor computing device , cellular telephone , pda , handheld or pen based computer , embedded appliance , and so forth . irrespective of its specific arrangement , station 120 can , for instance , comprise memory 212 , processing device 202 , a number of input / output interfaces 204 , wireless network interface device 206 , display 208 , and mass storage 222 , wherein each of these devices is connected across one or more data buses 210 . optionally , station 120 can also comprise a network interface device 220 also connected across one or more data buses 210 . processing device 202 can include any custom made or commercially available processor , a central processing unit ( cpu ) or an auxiliary processor among several processors associated with the computing device 120 , a semiconductor based microprocessor ( in the form of a microchip ), a macroprocessor , one or more application specific integrated circuits ( asics ), a plurality of suitably configured digital logic gates , or generally any device for executing instructions . input / output interfaces 204 provide any number of interfaces for the input and output of data . for example , where station 120 comprises a pc , these components may interface with user input device 204 , which may be a keyboard or a mouse . where station 120 comprises a handheld device ( e . g ., pda , mobile telephone ), these components may interface with function keys or buttons , a touch sensitive screen , a stylist , etc . display 208 can comprise a computer monitor or a plasma screen for a pc or a liquid crystal display ( lcd ) on a hand held device , for example . wireless network interface device 206 and optionally network interface device 220 comprises various components used to transmit and / or receive data over a network environment . by way of example , these may include a device that can communicate with both inputs and outputs , for instance , a modulator / demodulator ( e . g ., a modem ), wireless ( e . g ., rf ) transceiver , a telephonic interface , a bridge , a router , network card , etc . station 120 can use wireless network interface device 206 to communicate with access point 130 . with further reference to fig2 , memory 212 can include any one of a combination of volatile memory elements ( e . g ., random - access memory ( ram ), such as dram , and sram , etc .) and nonvolatile memory elements ( e . g ., flash , read only memory ( rom ), nonvolatile ram , etc .). mass storage 222 can also include nonvolatile memory elements ( e . g ., flash , hard drive , tape , cdrom , etc .) memory 212 comprises software which may include one or more separate programs , each of which includes an ordered listing of executable instructions for implementing logical functions . often , the executable code can be loaded from nonvolatile memory elements including from components of memory 212 and mass storage 222 . specifically , the software can include native operating system 214 , one or more native applications , emulation systems , or emulated applications for any of a variety of operating systems and / or emulated hardware platforms , emulated operating systems , etc . these may further include networking related software 216 which can further comprise a communications protocol stack comprising a physical layer , a link layer , a network layer and a transport layer . network related software 216 can be used by processing device 202 to communicate with access point 130 through wireless network interface 206 and can further include logic that causes the processor to receive instructions from an access point while disassociated with access point 130 . in particular , the software can receive a wakeup instruction from the access point even in a protected wireless network . the software can comprise logic that maps the length of encrypted payloads of protected frames into a message . it should be noted , however , that the logic for performing these processes can also be implemented in hardware or a combination of software and hardware . one of ordinary skill in the art will appreciate that the memory 212 can , and typically will , comprise other components which have been omitted for purposes of brevity . fig3 illustrates an embodiment of one of the access points shown in fig1 . it can be configured to receive and process messages as disclosed below . generally speaking , station 120 can comprise any one of a wide variety of network functions , including network address translation ( nat ), routing , dynamic host configuration protocol ( dhcp ), domain name services ( dns ) and firewall functions . irrespective of its specific arrangement , the stations 120 can , for instance , comprise memory 312 , a processing device 302 , wireless network interface 304 , network interface 306 , and nonvolatile storage 324 , wherein each of these devices is connected across one or more data buses 310 . processing device 302 can include any custom made or commercially available processor , a cpu or an auxiliary processor among several processors associated with access point 130 , a semiconductor based microprocessor ( in the form of a microchip ), a macroprocessor , one or more asics , a plurality of suitably configured digital logic gates , or generally any device for executing instructions . wireless network interface device 304 and network interface device 306 comprise various components used to transmit and / or receive data over a network environment . by way of example , either interface may include a device that can communicate with both inputs and outputs , for instance , a modulator / demodulator ( e . g ., a modem ), wireless ( e . g ., rf ) transceiver , a telephonic interface , a bridge , a router , network card , etc . access point 130 typically uses wireless network interface device 304 to communicate with nearby stations , and network interface device 306 to communicate with network 140 . in some implementation , the two devices can be combined into one physical unit . with further reference to fig3 , memory 312 can include any one of a combination of volatile memory elements ( e . g ., ram , such as dram , and sram , etc .) and nonvolatile memory elements ( e . g ., flash , rom , nonvolatile ram , hard drive , tape , cdrom , etc .). memory 312 comprises software which may include one or more separate programs , each of which includes an ordered listing of executable instructions for implementing logical functions . often , the executable code and persistent configuration parameters can be loaded from nonvolatile memory elements including from components of memory 312 . specifically , the software can include native operating system 314 , one or more native applications , emulation systems , or emulated applications for any of a variety of operating systems and / or emulated hardware platforms , emulated operating systems , etc . these may further include networking related software 322 which can further comprise a communications protocol stack comprising a physical layer , a link layer , a network layer and a transport layer . these may further include networking related software 316 which can further comprise a communications protocol stack comprising a physical layer , a link layer , a network layer and a transport layer . network related software 316 can be used by processing device 302 to communicate with access point 130 through wireless network interface 306 and can further include logic that causes the processor to receive messages broadcast to a special multicast address and retransmit the messages to nearby stations in unencrypted form regardless of whether access point 130 is operating on a protected wlan . it should be noted , however , that the logic for performing these processes can also be implemented in hardware or a combination of software and hardware . one of ordinary skill in the art will appreciate that the memory 312 can , and typically will , comprise other components which have been omitted for purposes of brevity . fig4 shows the format for a data frame . fields 402 , 404 , 406 , 408 , 410 , 412 , 414 and 416 are collectively referred to as the media access control ( mac ) header . frame control field 402 is a two octet fixed field indicative of properties of the frame as defined by the particular standard . it comprises a bit which when set indicates the frame is protected . duration / id field 404 is a two octet fixed field which comprises either duration information or identification information depending on the frame use as defined by the particular standard . address fields 406 , 408 , 410 , and 414 are used to specify various address parameters . typically in a multicast or broadcast application , address field 406 which is the receiver address is set to a multicast or broadcast address . address field 408 which is the sender address is usually set to the bssid . address field 410 which is the source address is set to the address of the sender of the frame . address field 414 is optional and is not used in a typical multicast or broadcast application . sequence control field 412 is a two octet fixed field which comprises a fragment number and a sequence number . the fragment number is used when a frame is fragmented to keep track of the fragments . the sequence number is incremented each time a station transmits a message . quality of service ( qos ) control field 416 is a two octet field used to carry qos parameters . after the mac header , the data frame includes frame body 418 which contains the payload . frame body 418 is encrypted as specified by the standard if the frame is protected . finally , frame check sequence field 420 is a four octet fixed field indicative of the integrity of the frame . the specific integrity check is specified by the standard , but as an example , some standards use a cyclic redundancy code ( crc ). referring to the architecture in fig1 , central computer 150 located somewhere on network 140 needs to wake up station 110 . the central computer prepares a multicast message and transmits it to a multicast address . access point 130 receives the multicast message addressed to multicast address and transmits it to stations within its range . if access point 130 is not a protected access point , then prior art methods to wake up station 110 could be used . however , if access point 130 is protected , if station 110 is in standby mode and disassociated with access point 130 , it cannot decrypt messages from access point 130 without reassociating with access point 130 which is costly in energy consumption as the station would have to roam and scan . due to the cost in resources , it is desirable to reassociate only if access point 130 has traffic for station 110 . this results in a vicious circle , that is , a station should not reassociate unless traffic is waiting for the station , but the station cannot know if there is traffic waiting for the station unless it reassociates . one solution uses a specially designated multicast address . many multicast addresses are designated for many purposes . for example , some are used for broadcast of media . there are also multicast addresses that are designated for specific purposes . these special multicast addresses are typical designated by a standards body and are used for a specific purpose . for example , there is a multicast address that is used for the specific purpose of address resolution . for this solution , there could be a multicast address specifically for waking up disassociated stations or generally for communicating with disassociated stations . this address could be any multicast address agreed upon by convention or at least agreed upon by the central computer and the stations , but preferably would be an address that is designated with a special purpose . while for the purposes of this disclosure , this address will be referred to as the wakeup multicast address , it is understood that the address could apply to the more general purpose of communicating with disassociated stations . in one embodiment , the access point upon receiving a multicast request through a network from a central computer , recognizes the destination address as a wakeup multicast address , that is , address frame 406 contains the wakeup multicast address . rather than encrypting the payload and transmitting a multicast data frame , the access point creates a multicast frame without encrypting the payload . a station in standby mode wakes up and checks the multicast frames . this wake up can take place periodically at predetermined times , such as in the usually broadcast and multicast opportunity that occurs after a delivery traffic indication map ( dtim ) beacon frame . when it sees a multicast frame with the destination address matching the wakeup multicast address , it recognizes the frame as a special multicast frame that is designated for disassociated stations . the station recognizes that the payload is not encrypted and can read the message . if the message is a wakeup message , the station can determine if it must wake up from the payload of the wakeup message . if so , the station reassociates with the access point and can now receive encrypted data designated for it . if the station determines it is not the intended recipient of the wakeup message , it can return to standby mode . one drawback of this embodiment is that the access points must be aware of the wakeup multicast address and conditionally apply encryption not to data frames destined for the wakeup multicast address . this would require the aps to be upgraded . this amounts to requiring an upgrade in the infrastructure . while this may be done through software / firmware updates . it is likely a change in the standards would need to be established to implement this approach . thus , it is desirable to have a solution where only the stations and the central computer need to be aware of the wakeup multicast frame , because such a solution would not require any infrastructure changes to be made . in another embodiment , a central computer transmits a multicast message to the access point . the payload of the message is a dummy message , however , the length of the payload is indicative of the station or group of stations to wake up , or in general the length of the payload is a message or part of a message to be transmitted to one or more disassociated clients . the central computer sends the message to all connected access point ( s ) with the wakeup multicast address as the destination . in the example of fig1 , central computer 150 would broadcast the wakeup message to access points 130 and 132 . the access point ( s ) receives the message but only recognizes the message as destined to a multicast address and not necessarily a multicast address with a special purpose . the access point encrypts the payload and transmits the multicast frame . when the station then receives the frame , it recognizes the wakeup multicast address and determines the length of the payload . depending on the implementation , the payload size may exclude header and encryption information added by the access point to encrypt the payload . in this manner , the central computer does not need to be aware of the added length created by the encryption process . the length can then be mapped to a station or group of stations for which the wakeup message is intended . the payload length can typically be varied between the order of 0 and 1500 bytes , or between 64 and 1500 bytes when the minimum ethernet packet size is taken into account , or between 8 and 1500 bytes when the logical link control / subnetwork access protocol ( llc / snap ) header is taken into account ( which is always present in 802 . 11 frames ), or between 28 and 1500 if the wakeup message is sent as an ip packet ( the ip header is 20 bytes , plus 8 for the llc / snap header ). therefore , to be more agnostic to the higher protocol layers , a range of 64 to 1500 should used . for the sake of the specific examples , a minimum of 64 and a maximum of 1500 are used . the use of these values should in no way be construed to limit the embodiments to this value . there are several approaches to mapping the payload length to a station . the most basic is to take the length and subtract the minimum length to obtain the index . for example , as depicted in fig5 , suppose the payload length is 121 and by convention the agreed minimum length is 64 , then station 57 ( 121 − 64 ) should wake up , where station 57 is the 57 th entry in a station list . another approach is to map the mac address through some function to yield a value between the minimum and maximum length . for example , the length can be associated with 64 + mac address mod 1436 to yield a length between 64 and 1500 . this runs the risk that by coincidence more than one station maps to the same length . under this situation , a station may awaken and reassociate unnecessarily . as the odds of this happening should be small , this mapping may be preferable as it eliminates the need to keep track of and maintain stations list . although the odds of coincidentally two stations on the same network being mapped to the same length should be remote , due to commonalities in the portions of the mac addresses , for example , there is a portion unique to each manufacturer , the probabilities may not be as remote . this can be resolved by first running the mac address through a cryptographic hash . thus , in the example above , the length is associated with 64 + hash ( mac address ) mod 1436 . fig6 a - d illustrate a multiple frame approach that can be used in the unlikely event 1436 values is not sufficient to convey the message to the desired station . the minimum length 64 is reserved as a continuation symbol . while the choice of the minimum length as a continuation symbol is used here , it is understood that equivalently any symbol between the minimum length and the maximum length could be used . fig6 a and 6b illustrate representations of values from 1 to 1435 . the mapping is similar to that given above except the minimum is set to 65 because the length 64 is reserved . fig6 a shows the representation of the value 57 . fig6 b shows the representation of the value 1435 . fig6 c illustrates how the value 1436 can be represented as 1436 is too large to be represented in a single frame . two frames are required . as the value is greater than 1435 , the first frame payload has a length of 64 which represents a continuation in counting from 1435 in the next frame payload . the length of the next frame payload is 65 which boils down to an offset value of 1 , but since the frame is a continuation frame , the value is 1435 plus the offset value . fig6 d illustrates the representation of the value 1600 . again since the value 1600 is greater than 1435 , a second frame is needed . frame 1 would comprise a payload of length 64 and frame 2 a payload of length 1600 − 1435 plus the 64 minimum that is 229 . the process could be extended to a third frame if the value to be represented is greater than 2870 , and so on . however , with the use of multiple frames it can be more efficient to set a smaller maximum value rather than 1500 and use more frames . for strings of more than two frames , a specific length value could be designated to demarcate the beginning of a sequence . fig7 is a flowchart describing the method of encoding a message based on the approach of fig6 a - d . the message in question is encoded as a number . one of ordinary skill in the art would recognize the equivalence between a message and its representation as a number . notationally , the number m is initially the representation of the message , and a maximum payload length and minimum payload length are represented by l max and l min , respectively . furthermore , to avoid cumbersome repetition in notation , the quantity l max − l min − 1 will be referred to as the encoding range . the encoding process begins at step 702 , where m is compared to the encoding range . if m is less than the encoding range , a dummy payload is created with length m + l min + 1 at step 704 , the payload can then be included in a protected frame possibly as part of a frame burst . this would end the encoding process . however , if m is greater than or equal to the encoding range , a dummy payload is created with length l min which can then be included in a protected frame possibly as part of a frame burst at step 706 . at step 708 , m is decremented by the encoding range . the process then repeats at step 702 . fig8 is a flowchart describing the corresponding method of decoding a message encoded in accordance with fig7 . the same notation is adopted for clarity . as each frame is received perhaps within the same burst . initially , m is set to zero at step 802 . at step 804 , the payload length from the next frame is derived shown as l payload . if l payload matches the continuation symbol which is l min in this example at step 806 , then m is incremented by the encoding range at step 810 and the process repeats at step 804 . however , if l payload is not equal to the continuation symbol , the process ends after m is incremented by l payload − l min − 1 at step 808 . the multiple frame approach of fig6 a - d is additive , that is , each additional frame gives the ability to address and add fixed number of values ( e . g . an additional 1435 values ). fig9 a - c show a multiplicative approach where each payload length encompasses 8 values representing three bits of information . a ninth value can be used as an end of message symbol . this shorter format enables the transmission of more data using shorter messages . specifically , in fig9 a , the value 411 which is 635 in octal needs to be expressed . the first frame has length 70 which corresponds to an offset of 6 from the minimum payload length , hence represents the octal digit 6 in the first digit of the octal value . the second frame has length 67 which corresponds to an offset of 3 from the minimum payload length , hence represents the octal digit 3 in the second digit of the octal value . the third frame has length 69 which corresponds to an offset of 5 from the minimum payload length , hence represents the octal digit 5 in the second digit of the octal value . finally a fourth frame has length 72 which corresponds to an offset of 8 from the minimum payload length which represents the end of value symbol . similarly , fig9 b and 9c illustrate the formatting of the values 56 and 98 , respectively . in general , the multiplicative approach splits the message into pieces based on some numeric base , ( e . g ., base 8 in the previous example ). while it is tempting for those skilled in the art to use a power of 2 for the base , any numeric base can be used . each piece is then encoded by adding the minimum payload length as an offset . the message is then terminated by an end of message symbol . alternatively , rather than specifying an end of message symbol the first frame could contain the number of frames representing the message . the general approach is similar to that illustrated in fig9 a - 9c . the message is split into pieces based on some numeric base . however , rather than expressing an end of message symbol in the last frame of the encoded message , the length of the message in frames is encoded in the payload of the first frame . examples that are counterparts to the examples of fig9 a - 9c are illustrated as fig1 a - 10c . the drawback to the multiple frame approaches is that sequence of the frames need to be tracked to insure the right information is tracked , but can be tracked by the sequence control frame 412 . while all the approaches above can transmit data to a disassociated station , the information rate for the amount of traffic generated is very low . the tradeoff between power usage , reassociation time and urgency of the message should be weighed . however , one of the most suitable uses is for breaking the encryption / reassociation dilemma by altering the station in standby mode to wake up , reassociate and receive an important encrypted message . it should be emphasized that the above - described embodiments are merely examples of possible implementations . many variations and modifications may be made to the above - described embodiments without departing from the principles of the present disclosure . all such modifications and variations are intended to be included herein within the scope of this disclosure and protected by the following claims .	8
the present invention now will be described more fully hereinafter with reference to the accompanying drawings , in which preferred embodiments of the invention are shown . this invention may , however , be embodied in many different forms and should not be construed as limited to the embodiments set forth herein ; rather , these embodiments are provided so that this disclosure will be thorough and complete , and will fully convey the scope of the invention to those skilled in the art . like numbers refer to like elements throughout . according to fig3 , a first driver 311 in a first integrated circuit 301 compares the respective logic levels of data d 0 and data d 1 , and generates a transmit signal vd 1 . when the logic levels of the data d 0 and d 1 are different , the first driver 311 generates the transmit signal vd 1 as a high voltage level . if the logic levels of the data d 0 and d 1 are the same , the first driver 311 generates the transmit signal vd 1 as a low voltage level . for example , when the logic level of the data d 0 is low and the logic level of the data d 1 is high , the first driver 311 generates the transmit signal vd 1 as a high voltage level . when both the logic levels of the data d 0 and d 1 are low , the first driver 311 generates the transmit signal vd 1 as a low voltage level . the transmit signal vd 1 generated by the first driver 311 is transmitted to a transmission line 331 via a pad 321 . the integrated circuit device 301 transmits data d 0 on a dummy transmission line 330 via the pad 320 . a first receiver 351 in a second integrated circuit 341 compares the data d 0 and the transmit signal vd 1 received as input via pads 361 and 362 , respectively , and recovers the data d 1 . the first receiver 351 calculates the absolute value of the difference between the voltage levels of the data d 0 and transmit signal vd 1 , and compares the absolute value of the difference with a threshold voltage . in a preferred embodiment , the voltage threshold is about 0 . 8 volts . when the absolute value is greater than the threshold voltage , the first receiver 351 outputs data of high voltage level . when the absolute value is less than the threshold voltage , the first receiver 351 outputs data of low voltage level . alternatively , the first driver 311 can generate a transmit signal vd 1 of low voltage level when the voltage levels of the data d 0 and d 1 are different , and generate a transmit signal vd 1 of high voltage level when they are the same . in this case , the first receiver 351 outputs the data d 1 as a low voltage level when the absolute value of the difference between the voltage levels of the data d 0 and the signal vd 1 input via the pads 361 and 362 , respectively , is greater than the threshold voltage . when the absolute value is less than the threshold voltage , the receiver 351 outputs the data d 1 as a high voltage level . a second driver 312 compares the voltage levels of the transmit signal vd 1 and data d 2 , and outputs the result as a transmit signal vd 2 . a third driver 313 compares the voltage levels of the transmit signal vd 2 and data d 3 with each other , and outputs the result as a transmit signal vd 3 . the operation of the second and third drivers 312 313 is analogous to the operation of the first driver 311 . the second receiver 352 compares the transmit signal vd 1 to the transmit signal vd 2 , and recovers the data d 2 , and a third receiver 353 compares the transmit signal vd 2 to the transmit signal vd 3 , and generates data d 3 . the operation of the second and third receivers 352 353 is analogous to the operation of the first receiver 351 . it will be understood that more drivers and receivers can be used . in another embodiment , the dummy transmission line 330 may be eliminated . in such an embodiment , for example , the first driver 311 receives the data d 1 and generates the transmit signal vd 1 either as the same voltage level as the data d 1 or as a different voltage level . also , the first receiver 351 receives only the transmit signal vd 1 and produces the data d 1 according to the voltage level of the signal vd 1 . fig4 is a circuit schematic diagram of the driver 311 of fig3 . a first detector circuit 411 receives data d 0 and d 1 , and includes a nand gate for performing a nand operation on the received data . a second detector circuit 421 receives the data d 0 and d 1 , and performs an or operation on the received data . that is , the second detector circuit 421 outputs a logic high when either the data d 0 and d 1 is logic high , and outputs a logic low when both the data d 0 and d 1 are logic low . the second detector circuit 421 includes a nor gate 423 and an inverter 425 . a transmit generator circuit 431 performs an and operation on the outputs of the first and second detector circuits 411 and 421 , and generates a signal vd 1 . that is , the transmit generator 431 generates the signal vd 1 as logic low when any one of the outputs of the first and second detector circuits 411 421 is a low logic level . when both of the outputs of the first and second detector circuits 411 421 are a high logic level , the transmit generator circuit 431 generates the signal vd 1 as a high logic level . as shown in fig3 , the transmit generator circuit 431 can include a nand gate 433 and an inverter 435 . referring to fig5 , the first receiver circuit 351 receives the data d 0 and the transmit signal vd 1 via resistors 521 , 523 , 525 and 527 , and provides the output data d 1 via an inverter 541 . the data d 0 is input to the gate of the nmos transistor 511 via the resistor 521 , and the transmit signal vd 1 is input to the gate of the nmos transistor 512 via the resistor 525 . accordingly , the nmos transistor 511 is turned on when the voltage level of the data d 0 is high , and is turned off when it is low . the nmos transistor 512 is turned on when the voltage level of the signal vd 1 is high , and is turned off when it is low . the output data d 1 is determined by the voltage level of the data d 0 and the voltage level of the transmit signal vd 1 . when the voltage levels of the data d 0 and transmit signal vd 1 are both low , the nmos transistors 511 and 512 are both turned off . the voltage level of a node n 1 becomes high via a supply voltage vcc , and is inverted by an inverter 541 , thereby causing the voltage level of the output data d 1 to become low . when the voltage level of the data d 0 is low , and the voltage level of the transmit signal vd 1 is high , the nmos transistor 511 is turned off , and the nmos transistor 512 is turned on . thus , the node n 1 is electrically coupled to the junction of the resistors 527 and 528 . the voltage level of the node n 1 becomes low , and is inverted by the inverter 541 , and thus the voltage level of the output data d 1 becomes high . when the voltage level of the data d 0 is high , and the voltage level of the signal vd 1 is low , the nmos transistor 511 is turned on , and the nmos transistor 512 is turned off . thus , the node n 1 is electrically coupled to the junction of the resistors 523 and 524 . the voltage level of the node n 1 becomes low , and is inverted by the inverter 541 , thereby causing the voltage level of the output data d 1 to become high . when the voltage levels of the data d 0 and vd 1 are both high , the nmos transistors 511 and 512 are both turned on . in this case , the sources of the nmos transistors 511 and 512 are each maintained at a high voltage level by the high voltage level signal vd 1 and data d 0 so that the voltage of the node n 1 is kept high when both the nmos transistors 511 and 512 are turned on . the voltage of the node n 1 is inverted by the inverter 541 , thereby causing the voltage level of the output data d 1 to become low . in operation of the first receiver 351 , if the absolute value of the difference between the voltage levels of the data d 0 and the signal vd 1 is higher than the voltage threshold , the voltage level of the output data d 1 becomes high . if the absolute value of the difference between the voltage levels of the data d 0 and the signal vd 1 is lower than the voltage threshold , the output data d 1 becomes logic low . when the inverter 541 is not used , if the absolute value of the difference between the voltage levels of the data d 0 and the signal vd 1 is higher than the voltage threshold , the voltage level of the output data d 1 becomes low . if the absolute value of the difference between the voltage levels of the data d 0 and the transmit signal vd 1 is lower than the voltage threshold , the voltage level of the output data d 1 becomes high . the voltage levels of the data d 2 and d 3 output by the second and third receivers 352 , 353 of fig3 can be the same or different depending on the characteristics of the second and third drivers 312 , 313 . the operation of the first receiver circuit 351 can , therefore , be summarized as shown below . accordingly , the likelihood of data loss can be reduced despite the presence of common mode noise . the use of one transmission line per receiver may simplify the structure of an embodiment according to the present invention . for example , as shown in fig3 , the first - third transmission lines 331 – 333 electrically couple the first - third drivers 311 – 313 and to the first – third receivers 351 – 353 respectively , which may simplify an embodiment according to the present invention , thereby allowing a reduction in manufacturing costs . in the drawings and specification , there have been disclosed typical preferred embodiments of the invention and , although specific terms are employed , they are used in a generic and descriptive sense only and not for purposes of limitation , the scope of the invention being set forth in the following claims .	7
treatment of tobacco plants with cell wall - degrading enzymes ( i . e . cellulases and pectinases ) leads to the induction of a subset of pr genes involved in the plant defence response ( palva et al ., 1993 ; vidal et al ., 1998 ). this induction occurs both in the local treated leaf and the distal uninfected leaves . furthermore , it has been shown that during plant - pathogen interactions there is er lumenal gene induction ( walter - larsen et al ., 1993 ; denecke et al ., 1995 ). the present invention is concerned primarily with the exact timing of chaperone induction in plants subjected to pathogen stress , which is simulated by treatment with cell wall - degrading enzymes ( cdes ). er chaperone gene induction occurs rapidly upon cde treatment on a local as well as systemic level which is faster than the pr gene activation . the invention is also concerned with elucidating the role of sa and its signal transduction pathway in this fast - acting induction mechanism , as this molecule is known to play an important role in establishing the pathogen defence mechanism ( ward et al ., 1991 ; delaney et al ., 1994 ; gaffney et al ., 1993 ). the parallel induction of er chaperones in the local and distal untreated leaves suggests the presence of a signal molecule or other such mechanism whereby a signal can be quickly transported throughout the whole plant . the results show that the systemic induction of er chaperones is not triggered by a feedback signal mechanism resulting from accumulation of newly synthesised proteins ( i . e . the upr ) in the local treated leaf . the early induction of bip is likely to depend on a feedforward mechanism in which the plant prepares itself for the folding of newly synthesised pr proteins exogenously applied sa leads to an induced resistance to erwinia carotovora subsp . carotovora in tobacco ( palva et al ., 1994 ). arabidopsis thaliana saii mutants which are abolished in their pr1 gene expression during sa treatment due to a mutation in the sa signal transduction pathway ( shah et al ., 1997 ) showed a normal cde - mediated bip induction . furthermore , transgenic nahg plants which contain the enzyme salicylate hydroxylase that converts sa into a non - active form showed similar cde - mediated bip gene expression as in the wt plants . this clearly demonstrates that sa is not involved in the local and systemic bip induction during cde treatment . other molecules like ethylene and jasmonate might be involved in the rapid induction of er chaperones as it is known that these compounds accumulate upon wounding and during pathogen attack thereby inducing a distinct set of genes which are thought to play a role in plant defence ( hyodo , 1991 ; reviewed by boller , 1991 ; creelman et al ., 1992 ; farmer et al ., 1992 ). it has been shown that the cde - induced defence response involves both the ethylene and signal transduction pathways ( vidal et al ., in preparation ). as ethylene and methyl jasmonate are both volatile , possible diffusion from the site of synthesis might occur , thereby acting in its gaseous form as the long distance signal . however , the role of both compounds in the early induction of bip gene expression has still to be established . therefore characterisation of bip gene induction in ethylene - insensitive mutants of arabidopsis would be a novel way to obtain more insight in the role of ethylene during cde treatment . the cde signal transduction pathway leading to the bip gene induction is independent of the β - 1 , 3 - glucanase signal transduction pathway as overproduction of the bip protein does not lead to induced β - 1 , 3 - glucanase transcript levels . this suggests that early in the cde signal transduction pathway bip differentiates from the β - 1 , 3 - glucanase signal transduction route leading to a rapid bip gene induction before that of pr genes . the plant therefore anticipates the need for more er chaperones necessary for the expected pr gene transcripts encoding secretory defence proteins on the rough er during defence reactions . the signal involved in the cde - mediated initiation of bip gene expression is still unknown although it is most likely to be independent of the upr and sa - mediated signal transduction pathway . besides cde treatment , sa also rapidly induces bip genes well before the pr genes . the sa - dependent induction of bip is distinct from that of the cde - mediated bip induction . the results show that the induction of bip upon pathogen attack is not merely a consequence of the increased synthesis of proteins on the rough er , but an early response of plant cells in order to prepare an adequate machinery for pr protein synthesis . the most crucial part of the invention concerns the contribution of the er chaperone bip in plant pathogen interactions and sar . bip induction occurs rapidly via an sa - mediated signal which also induces sar and pr protein synthesis , but the signal transduction pathway leading to bip is faster and independent of pr gene activation . this process operates in tobacco as well as aracbidopsis thaliana and is likely to be a conserved mechanism among plants . the sail mutant is incapable of sa - mediated pr1 induction but shows a normal sa - mediated rapid bip induction . artificially increased bip levels do not lead to pr1 induction in the absence of sa , which demonstrates that bip is not an earlier element of the sa - mediated signal transduction cascade leading to pr1 . however , artificially increased bip levels do have a synergistic action on the sa signal and accelerate pr1 induction to a give much faster response . working model for the role of bip in sa - mediated pr gene induction a model for the contribution of bip in the early response of plant cells to pathogen attack is illustrated in fig1 . when plants are attacked by a range of pathogens . sa levels increase and mediate sar and pr gene induction ( durner et al , 1997 ). many pr proteins such as chitinases , β - 1 , 3 ,- glucanases , pr1 , extension and pgip are secreted or vacuolar and are synthesised on the rough er . leaf mesophyll or epidermal cells in fully developed leaves do not secrete significant amounts of protein and have low levels of er chaperones ( vitale et al , 1993 ). therefore plants anticipate the need for more er protein folding machinery to accommodate the drastically increased concentration of transcripts encoding secretory defence proteins on the rough er during defence reactions . sa induces bip independently of pr genes via a branched signal transduction pathway , with the branching point being located upstream of saii . downstream of the branching point , elements of the signal transduction pathway leading to pr1 such as saii ( and others ) must be influenced by light and cell wall - degrading enzymes , none of which have an effect on the sa - mediated bip induction . in addition , a regulatory cross - talk between the two branches of the pathway exists to provide an additional regulatory mechanism to delay pr gene induction until bip levels are adequate . pr gene induction is either inhibited by low bip levels or induced by high bip levels in combination with sa . such a regulatory mechanism is beneficial to the plant cell as it ensures an upregulated er function before increased secretory protein synthesis commences in the defence response . this avoids an accumulation of translocation and folding intermediates of pr proteins in the er due to a lack of bip . bip is a key element in the early responses of plants to pathogen attack due to its requirement for the translocation and folding of proteins in the er and to constitute an important regulatory mechanism that delays pr protein synthesis on the rough er until the er lumen is adequately prepared with chaperones and folding enzymes . other er resident proteins such as pdi and calreticulin may be important as well as they too are induced , but since bip overexpression alone accelerates pr gene induction , bip is the key element in the regulation . bip should therefore be regarded as a novel target gene in early responses of plants to pathogen attack . bip overproducing plants have a higher viability and are more vigorous than the untransformed plants . overexpression of bip may have either positive effects on the ability to produce proteins , to grow faster and to resist a range of abiotic stresses such as frost , drought and salt stress . the inhibitory effect of low bip levels on pr gene expression is probably part of a more general regulatory mechanism to regulate protein synthesis on the rough er . synthesis of the secretory protein α - amylase is inhibited by er stress which limits the level of free bip . artificially increased bip levels do not show such an inhibition , demonstrating that high levels of bip are required for efficient α - amylase synthesis under stress . this phenomenon could be related to the retardation of pr gene induction until sufficient bip molecules are available . further results suggest that a novel negative pathway leads to a specific reduction of transcript levels corresponding to genes encoding secretory proteins , which means proteins synthesised by the rough er . overexpression of bip could thus have additional benefits besides increased pathogen resistance , for example in the production of secretory proteins in general ( of which pr proteins are merely a subset ). our experiments have shown that bip over - producers exhibit resistance to the bacteria causing soft rot in potatoes ( erwinia ), in that the bacteria has a reduced division rate in wounded parts of bip over - producers and so infection is reduced as compared to controls . in the field , where infection usually starts with just one bacterium , this difference may be crucial . additionally , we have observed that bip over - producers grow more rapidly , set seeds more rapidly and germinate more rapidly compared to controls , moreover cells prepared from bip over - producing plants have a higher capacity to produce protein than control plant cells . the following examples are provided to fully illustrate the present invention and should not be construed as limiting thereof . details of the materials and methods used are included after the specific examples . we have shown that treatment of tobacco plants with cell wall - degrading enzymes ( cde ) leads to the rapid induction of β - 1 , 3 - glucanase and other pr genes , both locally and systemically ( vidal et al , 1997 ). we have now repeated these experiments and monitored the er chaperone bip as well as β - 1 , 3 - glucanase , which was the most rapidly induced pr protein in this experimental system ( vidal et al , 1997 ). we used a commercial preparation of fungal cdes instead of custom made erwinia - derived hydrolases to increase reproducibility . one leaf from each tobacco plant was treated with cdes and the induction of bip gene expression was analysed in the treated ( local ) and untreated ( systemic ) leaves from the same plant . fig1 shows that bip transcripts accumulate rapidly , reaching a maximum after just 2 hours of incubation . this induction was observed locally as well systemically with the same timing and intensity . β - 1 , 3 - glucanase transcript accumulation is detectable only after 4 hours of incubation and reaches its plateau after 8 hours as described previously ( vidal et al , 1997 ). whereas bip induction is transient , β - 1 , 3 - glucanase mrna levels continue to be high after prolonged incubation times ( 24 - 48 hours ). similar patterns were obtained for pdi and calreticulin ( data not shown ) indicating that other reticuloplasmins are also induced both locally and systemically . our results clearly show that bip gene expression is induced locally as well systemically prior to the pr gene β - 1 , 3 - glucanase . the signal involved in the systemic response of bip gene expression must therefore be transported very rapidly from the local leaf to the distal leaves . as sa was shown to induce er chaperone expression ( denecke et al , 1995 ), we wanted to test if sa plays a role in the bip gene induction during treatment with cell wall - degrading enzymes . we used as sa - insensitive mutant of arabidopsis thaliana ( saii ) which no longer shows an induction of pr1 in the presence of sa ( shah et al , 1997 ). wt and saii mutants of the same ecotype were treated with cell wall - degrading enzymes and incubated for 6 hours . as a control ( con ), leaves were mock - infected with h 2 o . total rna was extracted and northern blot analysis was performed for bip and a hevein - like protein ( hel ) which is known to be induced by cdes of erwinia carotovora ( vidal et al , in preparation ). fig2 shows that wt arabidopsis thaliana plants show a specific cde - induced accumulation of bip transcripts ( compare with the mock infection ) as in tobacco plants . in the arabidopsis saii mutant , the bip gene expression exhibits exactly the same profile as seen in arabidopsis wt plants . transcripts of hel were also induced in wild - type plants . this demonstrates that either the mutation in the saii is downstream of the bip gene induction in an sa signal transduction pathway or that sa and the saii - dependent signal transduction pathway is not involved at all in the cde - mediated bip gene induction . both local and systemic induction of bip and glucanase by cell wall - degrading enzymes is sa independent although saii mutants are insensitive to sa it is known that they are still able to accumulate sa upon pathogen infection ( shah et al ., 1997 ). the previous experiment could not rule out completely the involvement of sa in the cde - mediated bip gene expression . to test this possibility , we used transgenic tobacco plants ( nahg ) that overexpress the enzyme salicylate hydroxylase which inactivates sa . it is clearly established that such plants are unable to accumulate sa ( gaffney et al ., 1993 ). after 6 and 24 hours of cde treatment , local and systemic leaves were harvested from unstransformed tobacco plants ( wt ) and nahg plants for rna extraction . as a positive control , the expression of β - 1 , 3 - glucanase was monitored because cde treatment will lead to its local and systemic induction independently of sa ( vidal et al ., 1997 ). our results clearly demonstrate that the presence of the nahg geneproduct has no influence on the cde - mediated bip induction ( fig3 ). this shows that sa is not involved in the signal transduction mechanism for both the local and the systemic induction of bip in this experimental system . as expected β - 1 , 3 - glucanase was induced locally and systemically in both wt and nahg plants when treated with cde as shown before ( vidal et al ., 1997 ). systemic induction of er chaperones is independent of the upr in local leaves even though bip induction occurs prior to β - 1 , 3 glucanase induction , we cannot rule out that other , as yet unidentified defence related proteins are induced more rapidly and perhaps before bip in our experimental system . if this were the case , it would still be possible that the rapid induction of bip is the result of a feedback mechanism due to er stress resulting from the increased synthesis of proteins on the rough er , the unfolded protein response ( upr ). in addition , a unique feature of the plant er is its continuity through the entire plant through the numerous plasmodesmata . we thus wanted to test if a upr triggered locally could result in a systemic upr in cells that do not suffer from er stress . we treated one leaf of a tobacco plant with the drug tunicamycin , which inhibits n - glycosylation of proteins in the er and causes the accumulation of malfolded proteins and the upr ( kosutsumi et al ., 1988 ; shamu et al ., 1997 ). as a negative control , tobacco leaves were mock - infected with h 2 o to examine possible induction of reticuloplasmin gene expression upon wounding whereas the positive control was the infection with cdes . total rna was extracted from the treated ( local ) leaves and the distal untreated ( systemic ) leaves after 3 and 8 hours of incubation . bip gene expression during mock - infection shows a slight induction after 3 hours of treatment in the local and systemic . this induction is shown to be transient and bip mrna levels return to their basic steady state levels after 8 hours ( fig4 ). β - 1 , 3 - glucanase mrna levels , however , do not increase at all during the mock - infection , confirming a minor influence of the wound response in our experimental system . treatment of tobacco leaves with cell wall - degrading enzymes shows a local and systemic induction of bip and β - 1 , 3 - glucanase genes , with the bip induction being the fastest response as seen in fig1 . when tobacco leaves are treated with tunicamycin a strong increase of bip mrna levels is observed after 3 and 8 hours in the treated leaf , but not the systemic leaf . this shows that the upr alone cannot constitute a systemic signal to induce bip in plants . the sytemic signal must thus be a novel compound that has yet to be identified . in addition , the expression of β - 1 , 3 - glucanase was neither locally nor systemically induced upon tunicamycin treatment , demonstrating that the upr is not involved in the production of defence related proteins either . we postulated that bip gene induction occurs via a feedforward mechanism in which the plant anticipates the need for more er chaperones for the folding of newly synthesised pr proteins . overexpression of bip is not sufficient to trigger the induction β - 1 , 3 - glucanase the more rapid induction of bip compared to β - 1 , 3 - glucanase and the otherwise similar expression profiles could suggest that bip is an element of the signal transduction cascade leading to the defence genes . to test this , we used transgenic plants which overproduce bip under the control of the strong constitutive cauliflower mosaic virus ( camv ) 35s promoter . these plants show a 142 - fold increase in bip transcript levels and a 5 - fold increased bip steady state protein level . if bip were part of the signal transduction cascade leading to the target gene β 1 , 3 - glucanase , bip overexpression alone should trigger β - 1 , 3 - glucanase gene induction . rna was extracted from untreated ( t = 0 ) and cde - treated ( 6 hours ) plants after which bip and β - 1 , 3 - glucanase are detected . fig5 shows that bip overproduction alone does not lead to the induction of β - 1 , 3 - glucanase ( compare lanes 0 with each other ). otherwise , β - 1 , 3 - glucanase was induced after 6 hours of cde treatment in both the wt and bip overproducing plants ( lane 6 wt and 89 ). the figure also illustrates the higher bip mrna levels in bip overproducing plants ( compare lanes 0 with each other ). the data clearly demonstrate that high bip protein levels do not replace the signal which leads to the β - 1 , 3 - glucanase gene induction during cde treatment . thus , bip is not part of the signal transduction pathway leading to β - 1 , 3 - glucanase . the unfolded protein response is additive to the cde response of bip and inhibits the expression of β - 1 , 3glucanase . to compare the cde - and upr - mediated induction of bip , we wanted to test if both stimuli are additive . for this purpose , we prepared protoplasts which are known to exhibit induced levels of β - 1 , 3 - glucanase ( denecke et al ., 1995 ). this is not surprising as protoplasts are prepared with cdes . these protoplasts were then treated with tunicanycin , to superimpose the upr onto the cde response . fig7 shows that both stimuli are additive , exhibited by a further induction of bip by tunicamycin . this suggests that both mechanisms are different . interestingly , β1 , 3 - glucanase expression is inhibited by tunicamycin . the additional er stress could trap bip in malfolded protein complexes , thus making it unavailable to promote pr protein synthesis on the rough er . the results suggested that although bip induction alone is not sufficient to trigger pr protein synthesis , sufficient bip levels are required to promote pr gene expression . it has been shown that sa is involved in the induction of pr genes ( reviewed by malamy and klessig , 1992 ) and that this signal molecule also induces the expression of er chaperones ( denecke et al , 1995 ). we wanted to investigate whether er chaperone induction is a consequence of the high synthesis rates of pr genes and used bip as a model system . tobacco plants were sprayed with sa ( 5 mm ) and the exact timing of the sa - mediated induction of pr - gene pri was compared to that of bip . pr1 was chosen as a representative marker for sa - mediated induction of pr genes as its response to sa is faster and more pronounced than that of acidic chitinase , basic chitinase and basic β - 1 . 3 glucanase ( vidal et al , 1997 ). fig7 a shows that the bip mrna levels are induced after 2 hours of treatment with sa and reach a plateau after 4 hours . in contrast sa - induced transcription of pr1 starts only after 6 - 8 hours and continues to accumulate upto 16 hours after treatment . at this time - point , bip mrna levels start to decrease again . we have shown previously that pr1 continuous to accumulate until 48 hours after sa treatment using the same experimental system ( vidal et al , 1997 ). similar patterns where obtained for pdi and calreticulin ( data not shown ) indicating that other reticuloplasmins are upregulated as well . the data also show that bip expression during sa - treatment is unlikely to be triggered by a feedback mechanism resulting from the presence of newly synthesised and perhaps malfolded or partially folded pr proteins in the er . bip protein levels were also shown to increase ( fig7 b ), with a significant increase noticeable after 4 - 6 hours of induction . to investigate further similarities and differences in the sa - mediated induction of bip and pr genes , we tested if the presence of light is required for the induction . the rationale for this experiment was derived from the observation that sa inhibits catalase , resulting in an increase of active oxygen species in the plant , which would then induce pr genes such as pr1 ( chen et al , 1993 ). despite the fact that the inhibition of catalase activity alone is not the key route by which pr1 is induced during sa - treatment ( chamnongpol et al , 1996 ), a cooperative interaction of sa and h 2 o 2 might lead to the strong induction of pr1 ( leon et al , 1995 , chen et al , 1995 ). since photorespiration is a major source of hydrogen peroxide in plant cells , sa would be a less effective inducer during darkness . tobacco plants were thus sprayed with sa ( 5 mm ) and incubated in the presence and absence of light for 6 and 16 hours . in the absence of light , bip showed hardly any reduction in the accumulation of mrna transcripts during sa - treatment whereas pr1 induction was almost completely abolished ( fig8 ). these data demonstrate that the sa - mediated induction of bip differs from that of pr1 . the data also confirm that bip mrna levels increase transiently and a significant decrease in mrna levels is detectable after 16 hours of treatment ( see also fig7 ). cell wall - degrading enzymes antagonise sa - mediated induction of pr1 but not bip we have shown that the sa - induced expression of pr1 is inhibited in a concentration dependent fashion by the presence of erwinia carotovora culture filtrate containing cell wall - degrading enzymes ( vidal et al , 1997 ). plant cell wall - degrading enzymes antagonise the effect of sa - dependent pr - gene expression via an unknown mechanism , and we wanted to test if cell wall - degrading enzymes had a similar antagonistic effect on sa - mediated bip expression . tobacco plants were therefore treated with a solution of 5 mm sa with or without cell wall - degrading enzymes ( 0 . 2 % macerozyme , 0 . 4 % cellulose ) as antagonists followed by a 6 and 16 hours incubation in the light . total rna was extracted and the expression of chaperones was determined in relation to pr1 . the results confirm that cell wall - degrading enzymes inhibit the sa - mediated pr1 expression ( fig9 ). quantification via phosphoimaging reveals that at 16 hours of incubation only 36 % of the signal is detected in the presence of cell wall - degrading enzymes , which corresponds well with previous findings ( vidal et al , 1997 ). in contrast , bip expression is not antagonised by the cell wall - degrading enzymes and appears even to be induced cooperatively after prolonged incubations ( 16 hours ). obviously , cell wall - degrading enzymes do not have a inhibitory effect on the sa - mediated bip expression . this suggests that bip is controlled by a different sa - dependent regulatory mechanism to pr1 . the unfolded protein response is additive to the sa response of bip in example 6 we have shown that the upr - induced bip gene expression is additive to the cell wall - degrading enzyme ( cde ) response . we now tested whether the sa - and upr - mediated induction of bip expression were additive as well . for this purpose , plants were sprayed with 5 mm sa and incubated for 12 h . to superimpose the upr onto the sa response , the sa - treated leaves were transferred to petridishes which contained ms medium with and without tunicamycin . after floating of the leaves for 2 . 5 h on this medium , rna was extracted and bip gene expression was analysed by northern blotting . fig1 shows that bip gene expression is strongly induced in the sa - treated plants ( compare lane con with lane sa − tu ). in addition , a further induction of bip transcription is established by tunicamycin treatment ( compare lane sa − tu with lane sa + tu ). this induction is due to the presence of tunicamycin in the ms medium and is not an artefact due to prolonged floating ( 2 . 5 h ) of the leaves on the medium as the negative control leaves ( sa − tu ) have floated as well 2 . 5 h on ms - medium without tunicamycin . the fact that , upon sa treatment , tunicamycin is still able to induce bip gene expression shows that both stimuli are additive which suggests that the two induction mechanisms are different . example 11 different signal transduction pathway are used for the induction of pr genes and bip to gain further insight into the signal transduction pathways leading to the induction of bip and pr1 , an sa non - responsive mutant of arabidopsis thaliana ( saii ) was used which does not express pr1 in the presence of sa ( shah et al , 1997 ). wt and saii mutants of the same ecotype were sprayed with sa ( 5 mm ) and incubated in the light . total rna was extracted and probed with the pr1 and bip gene from arabidopsis . the induction of pr1 in wt arabidopsis was detected 3 hours after sa - treatment and continued to increase until 8 hours ( fig1 ). bip showed the same expression profile as seen in tobacco plants when treated with sa . as in tobacco plants , bip mrna levels increase prior to pr1 transcripts in sa treated arabidopsis plants ( fig1 ) and diminish after prolonged incubations ( data not shown ). in the arabidopsis saii mutant , the pr1 induction was completely abolished during sa - treatment as expected ( shah et al , 1997 ). in contrast , bip mrna levels in the mutants showed exactly the same induction pattern as in the wild - type plant . this demonstrates that either a different sa - dependent signal transduction pathway is used to induce the bip gene , or that the regulatory protein which is defective in saii mutants is located downstream of the bip gene in the signal transduction pathway leading from sa to induced pr1 or bip gene induction . to distinguish between the two possible working models , we tested pr1 gene expression in transgenic plants carrying the bip coding region under the control of the strong constitutive cauliflower mosaic virus ( camv ) 35s promoter . if bip is simply located on the signal transduction pathway upstream of the saii mutation . bip overproduction alone should lead to induced pr1 gene expression . transgenic plants which show 5 - fold increased bip steady state protein levels and 142 - fold increased bip transcript levels were used to test basal pr1 mrna levels and sa - mediated pr1 induction . as shown in fig1 , basal bip mrna levels are much higher in the bip overproducing plants the weak induction by sa was unexpected but could be due to the influence of sa on the camv35s promoter itself ( qin et al , 1994 ). fig1 shows that the overproduction of bip alone does not replace the sa signal because it does not lead to induction of the pr1 gene ( compare lanes 0 with each other ). however , the bip overproducing plants show a more rapid pr1 induction upon sa treatment compared to the wild - type plant . together the results show that high bip levels in the er promote the sa - mediated pr1 induction but cannot replace the sa signal . this suggest that a branched signal transduction pathway leads to the induction of bip and pr1 upon sa treatment and that there is cross - talk between the two branches of the pathway . we have established a model system based on the comparison of protein biosynthesis in the cytosol and on the rough er using transient expression . a plasmid was constructed ( pnl200 , fig1 a ) containing two genes , one encoding the secreted barley α - amylase ( rogers , 1985 ) and the other encoding the cytosolic marker β - glucuronidase ( gus ; jefferson et al ., 1987 ). α - amylase was used to measure secretory protein biosynthesis , and gus was used to control for transfection efficiency and overall cell viability . we compared cells under normal culture conditions with cells subjected to er stress by treatment with tunicamycin . fig1 b shows that tunicamycin does not affect cell viability during the course of the experiment , as monitored with the internal marker gus , confirming previous results ( denecke et al ., 1990 ). in contrast , total α - amylase activity in the cell suspension was greatly reduced . since α - amylase is not glycosylated , tunicamycin should not have a direct effect on this protein . the tunicamycin effect is protein - specific and not dependent on the promoter used . therefore , we postulated that during tunicamycin stress , α - amylase synthesis , translocation , or folding is compromised . artificially increased bip levels alleviate er stress as measured by secretory protein production one possible explanation for the tunicamycin effect could be that bip is recruited by other malfolded proteins and is not available in sufficient quantities to promote optimal α - amylase synthesis , translocation , and folding . to test this hypothesis , we coexpressed bip to determine whether increased bip levels would alleviate the er stress and restore efficient α - amylase production . the protoplasts were coelectroporated with pnl200 and plasmids carrying ( 1 ) a gene encoding the bulk flow secretory marker phosphinothricin acetyltransferase ( sspat ; denecke et al ., 1990 ), ( 2 ) a bip overexpression construct ( pde800 ), or ( 3 ) a bip antisense construct ( pnl100 ). the bip isoform used in these experiments was the one that complemented the yeast kar2 mutant ( denecke et al ., 1991 ), whereas sspat is a neutral secretory protein used for control purposes . the protoplasts were incubated for 20 hours with and without tunicamycin and the activities of α - amylase and gus were measured . experiments were conducted in such a manner that similar internal marker activities ( gus ) were obtained in each experiment . the α - amylase activity of the total extract was then corrected with the final gus activities , and fig1 a shows the ratio of α - amylase activity to gus activity . if pat is coexpressed , tunicamycin leads to a reduction of α - amylase activities , as shown in fig1 . bip coexpression alone leads to slightly lower α - amylase activities compared to pat coexpression , but no further reduction of α - amylase activity was seen during tunicamycin treatment . coexpression of the antisense construct was indistinguishable from pat coexpression . fig1 b shows the percentage of α - amylase activity that remains after tunicamycin treatment and illustrates clearly that bip overexpression protects the cells from tunicamycin stress . er stress leads to a reduction of mrna levels corresponding to genes encoding secretory proteins fig1 shows that the transcript level of the vacuolar pr protein β - 1 , 3 - glucanase rapidly decreases during upr - induced bip transcription but begins to rise again when the bip mrna level has reached its maximum . during prolonged incubation times , transcript levels encoding secretory proteins recover to almost normal ( initial ) values again . identical results were obtained with other transcripts encoding the secretory proteins acidic chitinase and basic chitinase present in tobacco protoplasts , showing that the effect is not restricted to β - 1 , 3 - glucanase ( data not shown ). the data suggest that inhibition of secretory protein synthesis , observed during er stress ( fig1 ), occurs prior to translation . artificially increased bip levels alleviate er stress as measured by mrna levels corresponding to genes encoding secretory proteins fig1 a shows that in bip overexpressing tobacco protoplasts ( 89 ), no tunicamycin - mediated reduction of β - 1 , 3 - glucanase mrna levels is observed , consistent with the hypothesis that the effect is due to limiting amounts of bip . overexpression of a bip derivative lacking the er retention signal ( 801 ) only partially restores the β - 1 , 3 - glucanase mrna level under er stress conditions ( fig1 b ). this would be expected as the lack of a retention signal will result in a lower bip level in the er lumen . the result also suggest that it is the level of bip in the er lumen , and not the level of bip transcripts which is important in this respect as judged from our present results , two distinct mechanisms operate during a typical upr . one mechanism is the well established induction of expression of bip and other er chaperone genes during accumulation of unfolded proteins in the er ( shamu , 1997 ). a second mechanism ensures that secretory protein synthesis is held at a minimum at times when the amount of bip is limiting . this mechanism is post - transcriptional , and requires information to be present on the transcripts encoding secretory proteins . as soon as bip transcription is induced and sufficient bip is being synthesised to replenish the pool , the negative regulation is abolished and efficient secretory protein synthesis is permitted to take place once again . the proposed mechanism would limit er stress to a minimum . clearly , when the amount of bip is limiting , further protein synthesis on the rough er would cause additional er stress . this result could also explain the delay in pr gene induction until sufficient bip is available . plants of nicotiana tabacum cultivar petit havana ( maliga et al ., 1973 ) were axenically grown in ms medium ( murashige and skoog , 1962 ), 2 % sucrose in a temperature controlled room at 25 ° c . with a 16 h day / 8 h light regime and a light irradiance of 200 μe . m − 2 . s − 1 . arabidopsis thaliana nössen wt and saii plants ( shah et al ., 1997 ) were grown under the same conditions . plants were sprayed with 5 mm sa and 0 . 5 % tween 20 from all sides , ensuring contact on both sides of each leaf of the plant . typically , 10 ml of the sa solution was sprayed onto each plant . plants were then transferred from the 16 h day / 8 h night regime to constant light regime . protoplasts rnas were extracted as described by jones et al ., ( 1985 ). leaves were ground in frozen liquid nitrogen and transferred to ntes buffer ( 0 . 1 m nacl , 10 mm tris ph 7 . 5 , 1 mm edta , 1 % sds ). protoplasts samples were frozen in liquid nitrogen and thawed in ntes buffer . rna was extracted after adding an equal volume of phenol / chloroform . ethanol precipitation was carried out after incubation at − 20 ° c . for 16 hours . the pellet was resuspended and rna was selectively precipitated with licl ( 2m licl ) for 2 hours on ice . the pellet was washed with 70 % ethanol and resuspended in diethyl pyrocarbonate - treated water . gel blots of total rna denatured in formamide and formaldehyde were prepared . rna was blotted onto hybond - n membrane ( amersham corp ), as described by the manufacturer . a blp4 bip specific probe containing full length cdna , partial length bip2 were labelled using random prime dna synthesis using klenow fragment of dna polymerase i . hybridisation was performed as previously described ( denecke et al ., 1995 ). probes for tobacco bip ( denecke et al ., 1991 ), tobacco pr1a ( cornelissen et al ., 1986 ), arabidopsis bip and arabidopsis pr1a were prepared as described ( denecke et al ., 1995 ; vidal et al ., 1997 ). as a riboprobe , we used the 28s rna from asparagus , kindly provided by j . draper , university of wales , aberystwyth . fully expanded leaves were collected and quickly frozen in liquid nitrogen . frozen samples were then ground with a mortar and pestle . protein concentrations were determined using bio - rad protein assay reagent proteins in sds - polyacrylamide gels were transferred onto a nitrocellulose membrane and then blocked with pbs , 0 . 5 % tween 20 , and 5 % milk powder for 1 hr . the filter was then incubated in blocking buffer with primary antibody at a dilution of 1 / 5000 for anti - bip and anti - calreticulin antibodies . antibodies to barley α - amylase were used at a dilution of 1 / 10000 . after 1 hr , a 15 - min wash and three 5 min washes were done with 1 × pbs and 0 . 5 % tween 20 . the secondary antibody used was anti - rabbit antibody conjugated to horseradish peroxidase at a dilution of 1 / 5000 in 1 × pbs , 0 . 5 % tween 20 , and 5 % milk powder . the filter was incubated with the secondary antibody for 1 hr . washes were for 15 min , with 4 washes of 5 min with 1 × pbs and 0 . 5 % tween 20 followed by a final wash with 1 × pbs . detection of antigen - antibody complexes was performed with enhanced chemiluminescence ( ecl , amersham corp ), and the images were recorded on film . all dna manipulations were done according to established procedures . the escherichia coli mc1061 ampicillin - resistant strain ( casadaban and cohen , 1980 ) was used for the amplification of all plasmids . the plasmid pde203 containing the dual mannopine synthase ( mas ) promoter driving the chloramphenicol acetyltransferase ( cat ) gene and the β - glucuronidase ( gus ) gene is identical to pde222 ( denecke et al ., 1992 ), except for the presence of the cat coding region rather than the bar coding region . pde203 was digested with ncoi , filled in using the klenow fragment of dna polymerase i , and digested with hindiii . the α - amylase coding region was inserted as a blunt hindiii fragment , resulting in pnl200 ( fig7 ). the lumenal binding protein ( bip ) coding region of isoform blp4 ( denecke et al ., 1991 ) was amplified by polymerase chain reaction , creating an ncoi site overlapping with the translation initiation codon and a bamhi site just after the stop codon . this fragment was inserted between the cauliflower mosaic virus ( camv ) 35s promoter and the 3 ′ untranslated end of the nopaline synthase ( nos ) gene present on pde4 ( denecke et al ., 1990 ), resulting in pde800 . to obtain a bip antisense construct , pde800 was digested with ncoi and bamhi releasing the bip sequence , the vector was dephosphorylated using calf intestine alkaline phosphatase , and both vector and fragment were filled in . after gel purification , the two parts were ligated again . the plasmid containing the bip coding region in the antisense orientation was named pnl100 . chimeric genes containing the camv 35s promoter and the coding region of bip , in sense and antisense orientations , were ligated into the agrobacterium tumefaciens transformation vector pde 1001 ( denecke et al ., 1992 ). the pt plasmids were mobilised into the agrobacterium tumefaciens rifampicin - resistant strain c58 ( pgv2260 ) ( debleare et al ., 1985 ) using the kanamycin resistant e . coli helper strain hb101 ( prk2013 ). transformed plants were obtained by agrobacteria infection of leaf pieces with the respective strains . transformants were selected on murashige and skoog medium with 3 % sucrose containing 100 μg / ml kanamycin and 250 μg / ml cefotaxin . tobacco leaf protoplasts ( from transformed or untransformed plants ) were prepared , and electroporation experiments were performed as previously described ( denecke and vitale , 1995 ), with minor modifications to the electroporation conditions . the conditions used in these experiments were 910 μf and 130 v . these optimal conditions were established with the expression of the α - amylase gene in tobacco protoplasts . for each experiment 2 . 5 × 10 6 protoplasts were used with 20 to 40 μg of dna . after 24 or 48 hr , the protoplasts were analysed by enzymatic assay or by protein gel blotting . tunicamycin was used at a concentration of 20 μg / ml . harvesting of cells and culture medium was done as described previously ( denecke and vitale , 1995 ). α - 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( 1992 ). salicylic acid and plant disease reisistance . plant j . 2 , 643 - 654 . maliga , p ., breznowitz , a ., and marton , l . ( 1973 ). streptomycin - resistant plants from callus culture of haploid tobacco . nature 244 , 29 - 30 . mauch , f ., mauch - mani , b . and boller , t . ( 1988 ). antifungal hydrolases in pea tissue . ii . inhibition of fungal growth by combinations of chitinase and β - 1 . 3 glucanase . plant physiol . 88 , 936 - 942 . murashige , t . and skoog , f . ( 1962 ). a revised medium for rapid growth and bioassays with tobacco tissue culture . physiol . plant . 15 , 473 - 479 . palva , t . k ., holmström , k .- o ., heino , p ., and palva , e . t . ( 1993 ). induction of plant defense response by exoenzymes of erwinia crotovora subsp . crotovora mol . plant - microbe interact . 6 , 190 - 196 palva , t . k ., hurtig , m ., saindrenan , p ., and palva , e . t . ( 1994 ). salicylic induced resistance to erwinia crotovora subsp . crotovora in tobacco . mol . plant - microbe interact . 7 , 356 - 363 pérombelon , m . c . m . and salmond , g . p . c . ( 1995 ) bacterial soft rots . in pathogenesis and host specifity in plant diseases ( ed . u s sing , r p singh and k kohmoto ), 1 , 1 - 20 . oxford : pergamon qin , x . f ., holuigue , l ., horvath , d . m . and chua , n . h . ( 1994 ). immediate - early transcription activation by salicylic - acid via the cauliflowre mosaic - virus as - 1 element . plant cell 6 , 863 - 874 . rogers , j . ( 1985 ). two barley α - amylase gene families are regulated differently in barley aleurone cells . j . biol . chem . 260 , 3731 - 3738 . ross , a . f . ( 1961 ). localized acquired resistance to plant virus infection in hypersensitive hosts . vir 14 : 329 - 339 sela - buurlage , m . b ., ponstein , a . s ., bres - vloemans , s . a ., melchers , l . s ., van den elzen , p . j . m . and cornelissen , b . j . c . ( 1993 ) only specific tobacco ( nicotania tabacum ) chitinases and beta - 1 , 3 - glucanases exhibit antifungal activity . plant phys 101 , 857 - 863 shah , j ., tsui , f . and klessig d . f . ( 1997 ). characterization of a alicylic acid - insensitive mutant ( sail ) of arabidopsis thaliana , identified in a selective screen utilizing the sa - inducible expression of the tms2 gene . mol . plant - microbe interact . 10 , 69 - 78 . shamu , c . ( 1997 ). splicing together the unfolded - protein response . current biology 7 , r67 - 70 . vidal , s ., de leon , i . p ., denecke j . and palva , e . t . ( 1997 ). salicylic acid and the plant pathogen erwinia carotovora induce defense genes via antagonistic pathways . plant journal 11 , 115 - 123 . vidal , s ., eriksson , a . r . b ., montesano , m ., denecke , j . and palva , e . t . ( 1998 ) cell wall - degrading enzymes from erwinia carotovora cooperate in the salicylic acid - independent induction of a plant defense response . mol plant - microbe interact 11 , 232 - 32 vidal , s ., norman , c . and palva , e . t . cross - talk between ethylene , jasmonic acid and salicylic acid - dependent signal pathways regulates defense gene expression triggered by the plant pathogen erwinia carotovora . in preparation vitale , a ., ceriotti , a . and denecke , j . ( 1993 ). the role of the endoplasmic reticulum in protein systhesis , modification and intracellular transport . j . exp . bot ., 44 , 1417 - 1444 . vogel , j . p , misra , l . m ., and rose , m . d . ( 1990 ). loss of bip / grp78 function blocks translocation of secretory proteins in yeast j . cell biol . 110 , 1885 - 1895 . walther - larsen , h ., brandt , j ., collinge , d . b . and thordal - christensen , h . ( 1993 ) a pathogen - induced gene of barley encodes hsp90 homologue showing striking similarity to vertebrate forms resident in the endoplasmic reticulum . plant mol biol 21 , 1097 - 11098 ward , e . r ., uknes , s . j ., williams , s . c ., dincher , s . s ., wiederhold , d . l ., alexander , d . c ., ahl - goy , p ., métraux , j .- p . and ryals . j . a . ( 1991 ). coordinate gene activity in response to agents that induce systemic acquired resistance . plant cell 3 , 1085 - 1094 .	2
the compounds of the formula ( i ) may be used as such or , where appropriate , as pharmacologically acceptable salts ( acid or base addition salts ) thereof . the pharmacologically acceptable addition salts mentioned above are meant to comprise the therapeutically active non - toxic acid and base addition salt forms that the compounds are able to form . compounds that have basic properties can be converted to their pharmaceutically acceptable acid addition salts by treating the base form with an appropriate acid . exemplary acids include inorganic acids , such as hydrogen chloride , hydrogen bromide , hydrogen iodide , sulfuric acid , phosphoric acid ; and organic acids such as formic acid , acetic acid , propanoic acid , hydroxyacetic acid , lactic acid , pyruvic acid , glycolic acid , maleic acid , malonic acid , oxalic acid , benzenesulfonic acid , toluenesulfonic acid , methanesulfonic acid , trifluoroacetic acid , fumaric acid , succinic acid , malic acid , tartaric acid , citric acid , salicylic acid , p - aminosalicylic acid , pamoic acid , benzoic acid , ascorbic acid and the like . exemplary base addition salt forms are the sodium , potassium , calcium salts , and salts with pharmaceutically acceptable amines such as , for example , ammonia , alkylamines , benzathine , and amino acids , such as , e . g . arginine and lysine . the term addition salt as used herein also comprises solvates which the compounds and salts thereof are able to form , such as , for example , hydrates , alcoholates and the like . for clinical use , the compounds of the invention are formulated into pharmaceutical formulations for oral , rectal , parenteral or other mode of administration . pharmaceutical formulations are usually prepared by mixing the active substance , or a pharmaceutically acceptable salt thereof , with conventional pharmaceutical excipients . examples of excipients are water , gelatin , gum arabicum , lactose , microcrystalline cellulose , starch , sodium starch glycolate , calcium hydrogen phosphate , magnesium stearate , talcum , colloidal silicon dioxide , and the like . such formulations may also contain other pharmacologically active agents , and conventional additives , such as stabilizers , wetting agents , emulsifiers , flavouring agents , buffers , and the like . the formulations can be further prepared by known methods such as granulation , compression , microencapsulation , spray coating , etc . the formulations may be prepared by conventional methods in the dosage form of tablets , capsules , granules , powders , syrups , suspensions , suppositories or injections . liquid formulations may be prepared by dissolving or suspending the active substance in water or other suitable vehicles . tablets and granules may be coated in a conventional manner . in a further aspect the invention relates to methods of making compounds of any of the formulae herein comprising reacting any one or more of the compounds of the formulae delineated herein , including any processes delineated herein . the compounds of the formula ( i ) above may be prepared by , or in analogy with , conventional methods . the processes described above may be carried out to give a compound of the invention in the form of a free base or as an acid addition salt . a pharmaceutically acceptable acid addition salt may be obtained by dissolving the free base in a suitable organic solvent and treating the solution with an acid , in accordance with conventional procedures for preparing acid addition salts from base compounds . examples of addition salt forming acids are mentioned above . the compounds of formula ( i ) may possess one or more chiral carbon atoms , and they may therefore be obtained in the form of optical isomers , e . g . as a pure enantiomer , or as a mixture of enantiomers ( racemate ) or as a mixture containing diastereomers . the separation of mixtures of optical isomers to obtain pure enantiomers is well known in the art and may , for example , be achieved by fractional crystallization of salts with optically active ( chiral ) acids or by chromatographic separation on chiral columns . the chemicals used in the synthetic routes delineated herein may include , for example , solvents , reagents , catalysts , and protecting group and deprotecting group reagents . the methods described above may also additionally include steps , either before or after the steps described specifically herein , to add or remove suitable protecting groups in order to ultimately allow synthesis of the compounds . in addition , various synthetic steps may be performed in an alternate sequence or order to give the desired compounds . synthetic chemistry transformations and protecting group methodologies ( protection and deprotection ) useful in synthesizing applicable compounds are known in the art and include , for example , those described in r . larock , comprehensive organic transformations , vch publishers ( 1989 ); t . w . greene and p . g . m . wuts , protective groups in organic synthesis , 3 rd ed ., john wiley and sons ( 1999 ); l . fieser and m . fieser , fieser and fieser &# 39 ; s reagents for organic synthesis , john wiley and sons ( 1994 ); and l . paquette , ed ., encyclopedia of reagents for organic synthesis , john wiley and sons ( 1995 ) and subsequent editions thereof . the necessary starting materials for preparing the compounds of formula ( i ) are either known or may be prepared in analogy with the preparation of known compounds . the dose level and frequency of dosage of the specific compound will vary depending on a variety of factors including the potency of the specific compound employed , the metabolic stability and length of action of that compound , the patient &# 39 ; s age , body weight , general health , sex , diet , mode and time of administration , rate of excretion , drug combination , the severity of the condition to be treated , and the patient undergoing therapy . the daily dosage may , for example , range from about 0 . 001 mg to about 100 mg per kilo of body weight , administered singly or multiply in doses , e . g . from about 0 . 01 mg to about 25 mg each . normally , such a dosage is given orally but parenteral administration may also be chosen . the invention will now be further illustrated by the following specific examples . these examples are not limitative of the remainder of the disclosure in any way whatsoever . without further elaboration , it is believed that one skilled in the art can , based on the description herein , utilize the present invention to its fullest extent . all publications cited herein are hereby incorporated by reference in their entirety . 1 h nuclear magnetic resonance ( nmr ) and 13 c nmr were recorded on a bruker pmr 500 spectrometer at 500 . 1 mhz and 125 . 1 mhz , respectively or on a jeol eclipse 270 spectrometer at 270 . 0 mhz and 67 . 5 mhz , respectively , or on a bruker advance dpx 400 spectrometer at 400 . 1 and 100 . 6 mhz , respectively . all spectra were recorded using residual solvent or tetramethylsilane ( tms ) as internal standard . all spectra were recorded using residual solvent or tetramethylsilane ( tms ) as internal standard . ir spectra were recorded on a perkin - elmer spectrum 1000 ft - ir spectrometer . electrospray mass spectrometry ( ms ) were obtained using an agilent msd mass spectrometer . accurate mass measurements were performed on a micromass lct dual probe . elemental analyses were performed on a vario el instrument or sent to mikro kemi in uppsala . analytical hplc were performed on agilent 1100 . preparative hplc was performed on a gilson system or on a waters / micromass platform zq system . preparative flash chromatography was performed on merck silica gel 60 ( 230 - 400 mesh ). the compounds were automatically named using acd6 . 0 . gc - ms analysis was performed on a hewlett packard 5890 gas chromatograph with a hp - 5ms 15 m * 0 . 25 mm * 0 . 25 μm column connected to a 5971 ms detector . electrospray mass spectrometry ( ms ) spectra were obtained on a perkin - elmer api 150ex mass spectrometer . accurate mass measurements were performed on a micromass lct dual probe . a solution of the amine , ( 3as , 6r , 7as )- 1 - benzyl - 3a -( 3 , 4 - dimethoxyphenyl ) octahydro - 1h - indol - 6 - amine , comparative example 5 ( 18 . 3 mg ; 0 . 05 mmol ) in methylene chloride ( 2 . 0 ml ) was treated with an isocyanate or isothiocyanate ( 1 equiv . ; 0 . 05 mmol ) the mixture was shaken at room temperature for 18 h , then the solvent was removed by evaporation . a solution of the appropriate amine ( 1 mmol ) in dcm ( 5 . 0 ml ) was treated with para - nitrophenylchloroformate ( 1 mmol ). the resulting solution was then treated dropwise at room temperature with hunigs base ( 1 mmol ). the mixtures were stirred at room temperature for 5 h . an aliquot ( 0 . 25 ml ; 0 . 05 mmol ) of the crude pnp - carbamate from the reaction mixtures described above was then transferred to a solution of the amine , ( 3as , 6r , 7as )- 1 - benzyl - 3a -( 3 , 4 - dimethoxyphenyl ) octahydro - 1h - indol - 6 - amine , comparative example 5 ( 18 mg ; 0 . 05 mmol ) in methylene chloride ( 3 . 0 ml ) and the resulting solution shaken at r . t . overnight . the solvent was removed by evaporation and the crude reaction mixtures purified by preparative hplc . a solution of the amine , ( 3as , 6r , 7as )- 1 - methyl - 3a -( 3 , 4 - dimethoxyphenyl ) octahydro - 1h - indol - 6 - amine , comparative example 7 ( 7 . 3 mg ; 0 . 025 mmol ) in tetrahydrofuran ( 1 . 0 ml ) was treated with and isocyanate or isothiocyanate ( 1 equiv . ; 0 . 025 mmol ) the mixture was shaken at room temperature for 18 h , then the solvent was removed by evaporation . the amine , ( 3as , 6r , 7as )- 1 - methyl - 3a -( 3 , 4 - dimethoxyphenyl ) octahydro - 1h - indol - 6 - amine , comparative example 7 ( 7 mg , 0 . 024 mmol ) and isocyanate ( 1 . 3 eq ) were dissolved in dry thf ( 1 . 5 ml ). reaction in r . t ., under n 2 and overnight . the solvent was evaporated under reduced pressure . purification was performed by preparative hplc . to the appropiate amine ( 0 . 06 mmol ) in etoh ( 0 . 5 ml ) and thf ( 0 . 5 ml ) was added an aldehyde ( 0 . 1 mmol ) and nabh 3 cn ( 1 mmol ). the mixture was stirred overnight and concentrated . 2 m naoh was added and the aqueous layer extracted with etoac . the products were purified by preparative hplc . dimethoxyphenyl acetonitrile ( 4 . 43 g , 2 . 5 mmol ) was dissolved in dmf ( 20 ml ). sodium hydride ( 4 g of a 60 % dispersion , 2 . 4 g , 100 mmol ) was added in portions and the mixture was stirred at room temperature for 10 minutes . bromochloroethane ( 2 . 1 ml , 3 . 62 g , 25 . 2 mmol ) was added , and the mixture stirred at room temperature overnight . the reaction was cautiously quenched by addition of a methanol / water mixture ( 1 : 1 , 300 ml ) and the reaction products were extracted into ethyl acetate ( 3 × 200 ml ). the combined extracts were washed with water ( 4 × 200 ml ), brine ( 1 × 200 ml ) and then dried ( na 2 so 4 ). the solvent was then removed under reduced pressure and the crude product chromatographed ( sio 2 , etoac / petroleum ether 1 : 3 as eluent ) to give the title compound as an off - white solid ( 2 . 4 g , 47 %). 1 h nmr ( 270 mhz , cdcl 3 ) δ 1 . 32 ( m , 2h ) 1 . 64 ( m , 2h ) 3 . 84 ( s , 3h ) 3 . 88 ( s 3h ) 6 . 79 ( d , j = 1 . 0 hz , 2h ) 6 . 84 ( s 1h ). ms ( esi +) for c 12 h 13 no 2 : m / z 204 . 1 ( m + 1 ). 1 -( 3 , 4 - dimethoxyphenyl ) cyclopropanecarbonitrile , comparative example 1 ( 2 . 0 g , 9 . 84 mmol ) was dissolved in thf ( 30 ml ). dibal - h ( 15 ml of a 1 . 0 m solution in toluene , 15 mmol ) was added and the mixture was stirred at room temperature for 3 hours . the reaction was cautiously quenched by addition of 2 m hcl and organic components were extracted into dichloromethane ( 3 × 125 ml ). the combined extracts were washed with water ( 2 × 100 ml ), brine ( 2 × 100 ml ) and then dried ( na 2 so 4 ), giving the title compound as an off - white sold ( 1 . 95 g , 98 %). 1 h nmr ( 270 mhz , cdcl 3 ) δ ppm 1 . 38 ( m , 2h ) 1 . 53 ( m , 2h ) 3 . 87 ( s , 6h ) 6 . 81 ( s , 1h ) 6 . 84 ( d , j = 1 . 0 hz , 2h ) 9 . 23 ( s , 1h ). ms ( esi +) for c 12 h 14 o 3 : no ion detected . 1 -( 3 , 4 - dimethoxyphenyl ) cyclopropanecarbaldehyde , comparative example 2 ( 3 . 25 g , 16 . 0 mmol ) was dissolved in dichloromethane ( 35 ml ). benzylamine ( 1 . 77 ml , 1 . 74 g , 16 . 2 mmol ) was added , followed by sodium sulfate ( 15 g , 105 . 6 mmol ). the mixture was stirred at room temperature overnight before being filtered and evaporated to yield the crude imine as a clear oil . this material was then dissolved in dmf ( 15 ml ), and sodium iodide ( 246 mg , 1 . 64 mmol ) and trimethylsilyl chloride ( 202 μl , 172 mg , 1 . 58 mmol ) were added . the resulting mixture was heated to 70 ° c . for 3 hours and then partitioned between water ( 150 ml ) and ethyl acetate ( 200 ml ). the aqueous phase was extracted with a further portion of ethyl acetate ( 1 × 200 ml ) and the combined extracts were washed with brine ( 1 × 200 ml ) and dried ( na 2 so 4 ). the solvent was removed under reduced pressure , and the crude product dissolved in dichloromethane ( 30 ml ). to this was added hcl in ether ( 70 ml of a 1 . 0 m solution , 70 mmol ) and the crude hcl salt was evaporated to dryness . this material was then dissolved in acetonitrile ( 70 ml ), methyl vinyl ketone ( 1 . 42 ml , 1 . 19 g , 17 mmol ) was added and the mixture heated to reflux for 16 hours . on cooling the solvent was removed under reduced pressure and the resulting dark oil partitioned between 3m hcl solution ( 200 ml ) and ether ( 150 ml ). the aqueous fraction was washed with further ether ( 3 × 150 ml ), and then brought to basic ph using 3 m naoh solution . the organic components were then extracted into diethyl ether ( 3 × 150 ml ) and the combined extracts washed with brine ( 1 × 200 ml ) and dried ( na 2 so 4 ). on removal of the solvent under reduced pressure , the crude product was purified by chromatography ( sio 2 , ethyl acetate / petroleum ether 2 : 3 as eluent ) to give the title compound as a clear oil ( 3 . 10 g , 53 %). 1 h nmr ( 270 mhz , cdcl 3 ) δ ppm : 1 . 87 - 2 . 38 ( m , 6h ); ( 2 . 38 - 2 . 82 ( m , 3h ); 2 . 82 - 3 . 05 ( m , 1h ); 3 . 05 - 3 . 20 ( m , j = 12 . 6 hz , 1h ); 3 . 20 - 3 . 35 ( m , 1h ); 3 . 92 ( s , 6h ); 3 . 96 - 4 . 19 ( m , j = 12 . 6 hz , 1h ); 6 . 73 - 7 . 03 ( m , 3h ) 7 . 09 - 7 . 42 . 13 c nmr ( 68 mhz , cdcl 3 ) δ ppm : 34 . 80 , 36 . 21 , 38 . 61 , 40 . 63 , 47 . 18 , 51 . 67 , 53 . 38 , 57 . 38 , 60 . 32 , 68 . 15 , 109 . 90 , 110 . 95 , 117 . 76 , 126 . 89 , 128 . 15 , 128 . 76 , 138 . 79 , 140 . 32 , 147 . 47 , 148 . 98 , 211 . 36 . 1 -( 3 , 4 - dimethoxyphenyl ) cyclopropanecarbaldehyde , comparative example 2 ( 8 . 0 g , 38 . 8 mmol ) was dissolved in dichloroethane ( 100 ml ). sodium sulfate ( 25 g , 176 mmol ) was added and methylamine gas was bubbled through the solution for 10 minutes . the reaction vessel was then sealed and the mixture stirred at room temperature overnight before being filtered and evaporated to yield the crude imine as a yellow oil . this material was then dissolved in dmf ( 30 ml ), and sodium iodide ( 585 mg , 3 . 90 mmol ) and trimethylsilyl chloride ( 500 l , 426 mg , 3 . 92 mmol ) were added . the resulting mixture was heated to 90 ° c . for 3 hours and then partitioned between water ( 200 ml ) and ethyl acetate ( 200 ml ). the aqueous phase was extracted with a further ethyl acetate ( 2 × 100 ml ) and the combined extracts were dried ( na 2 so 4 ). the solvent was removed under reduced pressure , and the crude product dissolved in dichloromethane ( 100 ml ). to this was added hcl in ether ( 100 ml of a 1 . 0 m solution , 100 mmol ) and the crude hcl salt was evaporated to dryness . this material was then dissolved in acetonitrile ( 100 ml ), methyl vinyl ketone ( 3 . 5 ml , 2 . 95 g , 42 . 1 mmol ) was added and the mixture heated to reflux for 16 hours . on cooling the solvent was removed under reduced pressure and the resulting dark oil partitioned between 3m hcl solution ( 200 ml ) and ether ( 200 ml ). the aqueous fraction was washed with further ether ( 2 × 100 ml ), and then brought to basic ph using 3 m naoh solution . the organic components were then extracted into ethyl acetate ( 4 × 150 ml ) and the combined extracts washed with brine ( 1 × 200 ml ) and dried ( na 2 so 4 ). on removal of the solvent under reduced pressure , the crude product was purified by chromatography ( sio 2 , ethyl acetate as eluent ) to give the title compound as a yellow oil ( 4 . 5 g , 40 %). 1 h nmr ( 270 mhz , cdcl 3 ) δ ppm : 1 . 99 - 2 . 12 ( m , 2h ); 2 . 12 - 2 . 26 ( m , 3h ); 2 . 28 ( s , 3h ); 2 . 30 - 2 . 47 ( m , 2h ); 2 . 52 - 2 . 62 ( m , 2h ); 2 . 88 - 2 . 95 ( m , 1h ) 3 . 06 - 3 . 15 ( m , 1h ) 3 . 85 ( s , 3h ); 3 . 87 ( s , 3h ); 6 . 76 - 6 . 93 ( m , 3h ). 13 c nmr ( 68 mhz , cdcl 3 ) δ ppm : 35 . 20 , 36 . 16 , 38 . 76 , 40 . 01 , 40 . 48 , 47 . 42 , 54 . 78 , 55 . 82 , 55 . 92 , 70 . 31 , 109 . 84 , 110 . 87 , 117 . 83 , 140 . 12 , 147 . 39 , 148 . 90 , 211 . 40 . ms ( esi +) for c 17 h 23 no 3 m / z 290 . 2 ( m + h ) + . hrms ( ei ) calcd for c 17 h 23 no 3 : 289 . 1678 , found 289 . 1684 ( 3 as , 7as )- 1 - benzyl - 3a -( 3 , 4 - dimethoxyphenyl ) octahydro - 6h - indol - 6 - one ( comparative example 3 ) ( 750 mg , 2 . 05 mmol ) was dissolved in methanol ( 60 ml ). ammonium acetate ( 1 . 6 g , 20 . 8 mmol ) was added and the solution allowed to stir at room temperature for 2 hours before sodium cyanoborohydride ( 100 mg , 1 . 59 mmol ) was added . the mixture was stirred at room temperature for 16 hours , diluted with 3 m naoh solution ( 100 ml ) and extracted into dichloromethane ( 2 × 150 ml ). the combined extracts were dried ( na 2 so 4 ) and the solvent removed to give the crude mixture of amines ( 410 mg , 55 %). this crude material was used as a mixture without further purification , or the cis ( 6r )- and trans - isomer ( 6s ) separated by flash chromatography using chloroform saturated with nh 3 ( g ). same procedure as for comparative example 5 and comparative example 6 starting from ( 3as , 7as )- 3a -( 3 , 4 - dimethoxyphenyl )- 1 - methyloctahydro - 6h - indol - 6 - one ( comparative example 4 ). this crude material was used as a mixture without further purification , or the cis ( 6r )- and trans - isomer ( 6s ,) separated by flash chromatography using chloroform saturated with nh 3 ( g ). into a solution of comparative example 3 ( 3 . 0 g , 8 . 2 mmol ) and ( boc ) 2 o ( 3 . 0 g , 13 . 7 mmol ) in i - proh ( 200 ml ) was suspended 10 % pd on charcoal ( 0 . 8 g ), and the resulting mixture was vigorously agitated under h 2 ( 1 . 4 atm ) during 4 h at rt . the catalyst was filtered off and the filtrate was shaken with ps - trisamine ( 3 . 0 g , 4 mmol / g ) at rt overnight . the resin was filtered off and the solvent evaporated , leaving the title compound ( 2 . 4 g , 80 %) as a thick oil , which was used in the next step without further purification . 1 h nmr ( 270 mhz , cdcl 3 ): δ ppm 1 . 28 - 1 . 51 ( m , 9h ), 1 . 96 - 2 . 38 ( m , 6h ), 2 . 43 - 2 . 72 ( m , 1h ), 2 . 72 - 2 . 89 ( m , 1h ), 3 . 14 - 3 . 45 ( m , 1h ), 3 . 68 - 3 . 84 ( m , 6h ), 4 . 27 - 4 . 58 ( m , 1h ), 6 . 60 - 6 . 84 ( m , 3h ). 13 c nmr ( 270 mhz , cdcl 3 ): δ ppm 14 . 22 , 21 . 04 , 28 . 50 , 33 . 22 , 36 . 59 , 44 . 76 , 55 . 90 , 55 . 96 , 60 . 29 , 79 . 87 , 100 . 00 , 109 . 49 , 111 . 20 , 117 . 99 , 137 . 66 , 147 . 86 , 149 . 08 , 210 . 41 . the compounds were synthesised ( starting with 705 mg of the mixture of amines ) and purified in an analogous method to that described in example 14 and 15 to give : ms ( esi +) for c 26 h 35 n 3 o 2 s : m / z 454 . 0 ( m + 1 ) hrms ( ei ) calcd c 26 h 35 n 3 o 2 s : 453 . 2450 , found 453 . 2472 ms ( esi +) for c 26 h 35 n 3 o 2 s : m / z 454 . 0 ( m + 1 ) hrms ( ei ) calcd c 26 h 35 n 3 o 2 s : 453 . 2435 , found 453 . 2450 compounds were prepared and purified in an analougous method to that described in example 14 and 15 to give : ms ( esi +) for c 28 h 39 n 3 o 2 s : m / z 482 . 1 ( m + 1 ) hrms ( ei ) calcd c 28 h 39 n 3 o 2 s : 481 . 2763 , found 481 . 2765 ms ( esi +) for c 28 h 39 n 3 o 2 s : m / z 482 . 1 ( m + 1 ) hrms ( ei ) calcd c 28 h 39 n 3 o 2 s : 481 . 2763 , found 481 . 2742 the mixture of cis and trans amines from comparative example 5 and comparative example 6 ( 82 . 5 mg , 225 μmol ) was dissolved in dichloromethane ( 5 ml ). benzyl isothiocyanate ( 39 μl , 43 . 9 mg , 294 μmol ) was added and the mixture stirred at room temperature for 16 hours . the solvent was then removed , and the crude reaction mixture chromatographed ( sio 2 , petroleum ether / ethyl acetate 5 : 2 as eluent ) to give : ms ( esi +) for c 31 h 37 n 3 o 2 s : m / z 516 . 2 ( m + 1 ) hrms ( ei ) calcd c 31 h 37 n 3 o 2 s : 515 . 2606 , found 516 . 2602 ms ( esi +) for c 31 h 37 n 3 o 2 s : m / z 516 . 2 ( m + 1 ) hrms ( ei ) calcd c 31 h 37 n 3 o 2 s : 515 . 2606 , found 516 . 2623 the compound was synthesised and purified an analougous method to that described in example 14 and 15 to give : ms ( esi +) for c 26 h 35 n 3 o 3 : m / z 438 . 5 ( m + 1 ) hrms ( ei ) calcd c 26 h 35 n 3 o 3 : 437 . 2678 , found 437 . 2670 nh 4 oac ( 2 g ) was added to a solution of tert - butyl ( 3as , 7as )- 3a -( 3 , 4 - dimethoxyphenyl )- 6 - oxooctahydro - 1h - indole - 1 - carboxylate ( comparative example 9 , 2 . 4 g , 6 . 4 mmol ) in meoh ( 50 ml ), and the solution was stirred at ambient temperature for 2 h before nabh 3 cn ( 400 mg ) was added and the mixture stirred overnight . the mixture was diluted with 3 m naoh ( 50 ml ) and extracted with dichloromethane . the crude mixture of amines was used without further purifications . benzyl thioisocyanate ( 1 . 5 eqv .) was added to a solution of the amine mixture from above ( 0 . 1 g , 0 . 26 mmol ) in chcl 3 ( 50 ml ) and the mixture was stirred at ambient temperature overnight . trisamine - ps ( 1 g ) was added and the mixture stirred for 4 h before filtration and separation of products by flash chromatography ( silica , chcl 3 / meoh / nh 3 ). first eluted . tert - butyl ( 3as , 6r , 7as )- 6 -{[( benzylamino ) carbonothioyl ] amino }- 3a -( 3 , 4 - dimethoxyphenyl ) octahydro - 1h - indole - 1 - carboxylate : 215 mg . 1 h nmr ( 270 mhz , cdcl 3 ): δ ppm 1 . 13 - 1 . 53 ( m , 10h ), 1 . 65 - 1 . 99 ( m , 4h ), 1 . 99 - 2 . 23 ( m , 1h ), 2 . 92 - 3 . 31 ( m , 1h ), 3 . 31 - 3 . 66 ( m , 3h ), 3 . 77 - 3 . 94 ( m , 6h ), 3 . 96 - 4 . 15 ( m , 1h ), 4 . 74 - 5 . 01 ( m , 1h ), 5 . 79 - 5 . 96 ( m , 1h ), 6 . 74 - 6 . 91 ( m , 3h ), 7 . 18 - 7 . 34 ( m , 3h ), 7 . 34 - 7 . 44 ( m , 1h ), 7 . 44 - 7 . 70 ( m , 1h ). ( esi +) m / z 526 ( m + 1 ). hrms ( ei ) calc for c 32 h 36 f 3 n 3 o 3 s : 525 . 2661 ; found 525 . 2662 . to a solution of example 17 ( 600 mg , 1 . 14 mmol ) in dcm ( 20 ml ) was added trifluoroacetic acid ( 20 ml ) and the resulting solution was stirred at rt during 5 min . the volatiles were evaporated under reduced pressure and the residue was partitioned between etoac ( 5 ml ) and naoh ( aq ., 1m , 2 ml ). the water phase was extracted with etoac and the organic phases were washed with saturated aqueous nacl ( 2 ml ), dried ( mgso 4 ) and evaporated to give the title compound ( 0 . 44 g , 91 %) as a colorless oil . 1 h nmr ( 270 mhz , cdcl 3 ): δ ppm 1 . 01 - 1 . 15 ( m , 1h ), 1 . 15 - 1 . 42 ( m , 1h ), 1 . 56 - 1 . 68 ( m , 1h ), 1 . 72 - 1 . 89 ( m , 2h ), 1 . 90 - 2 . 15 ( m , 4h ), 2 . 20 - 2 . 33 ( m , 1h ), 2 . 34 - 2 . 45 ( m , 1h ), 3 . 09 - 3 . 22 ( m , 1h ), 3 . 22 - 3 . 40 ( m , 1h ), 3 . 77 - 3 . 97 ( m , 6h ), 4 . 17 - 4 . 39 ( m , 1h ), 4 . 59 - 4 . 94 ( m , 2h ), 5 . 67 - 6 . 16 ( m , 1h ), 6 . 65 - 6 . 94 ( m , 3h ), 7 . 18 - 7 . 40 ( m , 5h ). ms ( esi +) m / z 426 ( m + 1 ). hrms ( ei ) calc for c 24 h 31 n 3 o 2 s : 425 . 2137 ; found 425 . 2157 . following the general procedure for reductive alkylation of the pyrrolidine moiety , scheme e , using n - benzyl - n ′-[( 3 as , 6r , 7as )- 3a -( 3 , 4 - dimethoxyphenyl ) octahydro - 1h - indol - 6 - yl ] thiourea ( example 19 , 20 mg , 0 . 051 mmol ) and quinoline - 3 - carbaldehyde ( 0 . 25 mmol ), gave the title compound after preparative hplc purification . 1 h nmr ( 270 mhz , cdcl 3 ): δ ppm 1 . 04 - 1 . 26 ( m , 1h ), 1 . 26 - 2 . 61 ( m , 8h ), 2 . 83 - 3 . 20 ( m , 3h ), 3 . 20 - 3 . 38 ( m , 1h ), 3 . 69 - 3 . 91 ( m , 6h ), 4 . 27 - 4 . 67 ( m , 3h ), 4 . 77 - 4 . 99 ( m , 2h ), 5 . 21 - 5 . 46 ( m , 1h ), 5 . 75 - 6 . 07 ( m , 1h ), 6 . 68 - 6 . 90 ( m , 3h ), 7 . 40 - 7 . 58 ( m , 2h ), 7 . 58 - 7 . 69 ( m , 1h ), 7 . 72 - 7 . 87 ( m , 1h ), 7 . 99 - 8 . 21 ( m , 3h ), 8 . 81 - 8 . 81 - 8 . 92 ( m , 1h ). ms ( esi +) m / z 567 ( m + 1 ). hrms ( ei ) calc for c 34 h 38 n 4 o 2 s : 566 . 2715 ; found 566 . 2695 . following the general procedure for reductive alkylation of the pyrrolidine moiety , scheme e , using n - benzyl - n ′-[( 3as , 6r , 7as )- 3a -( 3 , 4 - dimethoxyphenyl ) octahydro - 1h - indol - 6 - yl ] thiourea ( example 19 , 20 mg , 0 . 051 mmol ) and 3 -( trifluoromethyl ) benzaldehyde ( 0 . 25 mmol ), gave the title compound after preparative hplc purification . 11h nmr ( 270 mhz , cdcl 3 ): δ ppm 1 . 01 - 1 . 17 ( m , 1h ), 1 . 24 - 1 . 59 ( m , 3h ), 1 . 59 - 1 . 85 ( m , 3h ), 1 . 85 - 2 . 51 ( m , 4h ), 2 . 81 - 3 . 24 ( m , 3h ), 3 . 67 - 3 . 92 ( m , 6h ), 4 . 10 - 4 . 33 ( m , 1h ), 4 . 33 - 4 . 70 ( m , 3h ), 5 . 20 - 5 . 57 ( m , 1h ), 5 . 72 - 6 . 05 ( m , 2h ), 6 . 66 - 6 . 91 ( m , 3h ), 7 . 19 - 7 . 85 ( m , 7h ). ( esi +) m / z 584 ( m + 1 ). hrms ( ei ) calc for c 32 h 36 f 3 n 3 o 2 s : 583 . 2480 ; found 583 . 2487 following the general procedure for reductive alkylation of the pyrrolidine moiety , scheme e , using n - benzyl - n ′-[( 3 as , 6r , 7as )- 3a -( 3 , 4 - dimethoxyphenyl ) octahydro - 1h - indol - 6 - yl ] thiourea ( example 19 , 20 mg , 0 . 051 mmol ) and 4 -( trifluoromethoxy ) benzaldehyde ( 0 . 25 mmol ), gave the title compound after preparative hplc purification . 1 h nmr ( 270 mhz , cdcl 3 ): δ ppm 1 . 03 - 1 . 29 ( m , 1h ), 1 . 30 - 1 . 49 ( m , 1h ), 1 . 49 - 1 . 66 ( m , 2h ), 1 . 66 - 1 . 91 ( m , 3h ), 1 . 91 - 2 . 35 ( m , 3h ), 2 . 35 - 2 . 60 ( m , 1h ), 2 . 83 - 3 . 22 ( m ; 3h ), 3 . 72 - 3 . 97 ( m , 6h ), 4 . 09 - 4 . 34 ( m , 1h ), 4 . 34 - 4 . 76 ( m , 2h ), 5 . 75 - 6 . 02 ( m , 1h ), 6 . 73 - 6 . 95 ( m , 3h ), 7 . 05 - 7 . 19 ( m , 2h ), 7 . 20 - 7 . 34 ( m , 5h ), 7 . 34 - 7 . 49 ( m , 2h ). ms ( esi +) m / z 600 ( m + 1 ). hrms ( ei ) calc for c 32 h 36 f 3 n 3 o 3 s : 599 . 2429 ; found 599 . 2443 following the general procedure for reductive alkylation of the pyrrolidine moiety , scheme e , using n - benzyl - n ′-[( 3as , 6r , 7as )- 3a -( 3 , 4 - dimethoxyphenyl ) octahydro - 1h - indol - 6 - yl ] thiourea ( example 19 , 20 mg , 0 . 051 mmol ) and 3 - phenylpropanal ( 0 . 25 mmol ), gave the title compound as a colorless after preparative hplc purification . 1 h nmr ( 270 mhz , cdcl 3 ): δ ppm 0 . 95 - 1 . 42 ( m , 3h ), 1 . 42 - 1 . 87 ( m , 6h ), 1 . 87 - 2 . 35 ( m , 5h ), 2 . 35 - 3 . 04 ( m , 4h ), 3 . 07 - 3 . 31 ( m , 1h ), 3 . 65 - 3 . 97 ( m , 6h ), 4 . 35 - 4 . 80 ( m , 2h ), 5 . 28 - 6 . 01 ( m , 1h ), 6 . 60 - 6 . 91 ( m , 3h ), 6 . 91 - 7 . 44 ( m , 10h ). ms ( esi +) m / z 544 ( m + 1 ). hrms ( ei ) calc for c 33 h 41 n 3 o 2 s : 543 . 2919 ; found 543 . 2902 . following the general procedure for reductive alkylation of the pyrrolidine moiety , scheme e , using n - benzyl - n ′-[( 3as , 6r , 7as )- 3a -( 3 , 4 - dimethoxyphenyl ) octahydro - 1h - indol - 6 - yl ] thiourea ( example 19 , 20 mg , 0 . 051 mmol ) and pyridine - 3 - carbaldehyde ( 0 . 25 mmol ), gave the title compound as a colorless oil after preparative hplc purification . 1 h nmr ( 270 mhz , cdcl 3 ): δ ppm 1 . 01 - 1 . 40 ( m , 3h ), 1 . 43 - 1 . 60 ( m , 2h ), 1 . 67 - 1 . 78 ( m , 3h ), 1 . 91 - 2 . 04 ( m , 1h ), 2 . 04 - 2 . 26 ( m , 2h ), 2 . 37 - 2 . 50 ( m , 1h ), 2 . 83 - 2 . 99 ( m , 1h ), 2 . 99 - 3 . 14 ( m , 2h ), 3 . 62 - 3 . 69 ( m , 1h ), 3 . 76 - 3 . 87 ( m , 7h ), 4 . 12 - 4 . 27 ( m , 1h ), 4 . 36 - 4 . 62 ( m , 2h ), 5 . 77 - 5 . 97 ( m , 1h ), 6 . 71 - 6 . 71 - 6 . 84 ( m , 3h ), 6 . 96 - 7 . 00 ( m , 1h ), 7 . 38 - 7 . 42 ( m , 1h ), 7 . 71 - 7 . 85 ( m , 5h ), 8 . 40 - 8 . 45 ( m , 1h ), 8 . 47 - 8 . 53 ( m , 1h ). ms ( esi +) m / z 517 ( m + 1 ). hrms ( ei ) calc for c 30 h 36 n 4 o 2 s : 516 . 2559 ; found 516 . 2557 . following the general procedure for reductive alkylation of the pyrrolidine moiety , scheme e , using n - benzyl - n ′-[( 3as , 6r , 7as )- 3a -( 3 , 4 - dimethoxyphenyl ) octahydro - 1h - indol - 6 - yl ] thiourea ( example 19 , 20 mg , 0 . 051 mmol ) and 4 - methoxybenzaldehyde ( 0 . 25 mmol ), gave the title compound as a colorless oil after preparative hplc purification . 1 h nmr ( 270 mhz , cdcl 3 ): δ ppm 1 . 01 - 1 . 15 ( m , 1h ), 1 . 26 - 1 . 43 ( m , 1h ), 1 . 43 - 1 . 63 ( m , 2h ), 1 . 63 - 1 . 85 ( m , 3h ), 1 . 85 - 2 . 16 ( m , 2h ), 2 . 16 - 2 . 43 ( m , 1h ), 2 . 84 - 3 . 20 ( m , 3h ), 3 . 66 - 3 . 77 ( m , 3h ), 3 . 77 - 3 . 92 ( m , 6h ), 3 . 95 - 4 . 18 ( m , 1h ), 4 . 37 - 4 . 73 ( m , 2h ), 5 . 28 - 5 . 62 ( m , 1h ), 5 . 62 - 5 . 99 ( m , 1h ), 6 . 62 - 6 . 62 - 6 . 95 ( m , 5h ), 7 . 03 - 7 . 44 ( m , 7h ). hrms ( ei ) calc for c 32 h 39 n 3 o 3 s : 545 . 2712 ; found 545 . 2712 . following the general procedure for reductive alkylation of the pyrrolidine moiety , scheme e , using n - benzyl - n ′-[( 3as , 6r , 7as )- 3a -( 3 , 4 - dimethoxyphenyl ) octahydro - 1h - indol - 6 - yl ] thiourea ( example 19 , 20 mg , 0 . 051 mmol ) and ethyl glyoxalate ( 0 . 25 mmol ), gave the title compound as a colorless oil after preparative hplc purification . 1 h nmr ( 270 mhz , cdcl 3 ): δ ppm 1 . 04 - 1 . 14 ( m , 3h ), 1 . 18 - 1 . 26 ( m , 11h ), 1 . 34 - 1 . 43 ( m , 11h ), 1 . 43 - 1 . 54 ( m , 2h ), 1 . 68 - 1 . 76 ( m , 1h ), 1 . 76 - 1 . 85 ( m , 2h ), 1 . 89 - 2 . 13 ( m , 3h ), 2 . 45 - 2 . 69 ( m , 1h ), 2 . 98 - 3 . 50 ( m , 4h ), 3 . 64 - 3 . 78 ( m , 1h ), 3 . 78 - 3 . 83 ( m , 6h ), 3 . 86 - 3 . 97 ( m , 1h ), 3 . 97 - 4 . 20 ( m , 1h ), 4 . 57 - 4 . 94 ( m , 2h ), 5 . 44 - 4 . 94 - 5 . 77 ( m , 1h ), 6 . 66 - 6 . 85 ( m , 3h ), 7 . 22 - 7 . 35 ( m , 5h ). ms ( esi +) m / z 512 ( m + 1 ). hrms ( ei ) calc for c 28 h 37 n 3 o 4 s : 511 . 2505 ; found 511 . 2518 . following the general procedure for reductive alkylation of the pyrrolidine moiety , scheme e , using n - benzyl - n ′-[( 3as , 6r , 7as )- 3a -( 3 , 4 - dimethoxyphenyl ) octahydro - 1h - indol - 6 - yl ] thiourea ( example 19 , 20 mg , 0 . 051 mmol ) and 4 - nitrobenzaldehyde ( 0 . 25 mmol ), gave the title compound as a colorless oil after preparative hplc purification . 1 h nmr ( 270 mhz , cdcl 3 ): δ ppm 1 . 04 - 1 . 84 ( m , 9h ), 1 . 89 - 2 . 28 ( m , 3h ), 2 . 33 - 2 . 57 ( m , 1h ), 2 . 72 - 3 . 00 ( m , 1h ), 3 . 00 - 3 . 23 ( m , 2h ), 3 . 70 - 3 . 89 ( m , 6h ), 4 . 14 - 4 . 67 ( m , 4h ), 5 . 19 - 5 . 37 ( m , 1h ), 5 . 67 - 6 . 02 ( m , 1h ), 6 . 51 - 6 . 62 ( m , 1h ), 6 . 69 - 6 . 87 ( m , 3h ), 7 . 20 - 7 . 36 ( m , 3h ), 7 . 48 - 7 . 64 ( m , 2h ), 7 . 70 - 7 . 85 ( m , 1h ), 8 . 04 - 8 . 14 ( m , 3h ), 8 . 15 - 8 . 32 ( m , 1h ). ms ( esi +) m / z 544 ( m + 1 ). following the general procedure for reductive alkylation of the pyrrolidine moiety , scheme e , using n - benzyl - n ′-[( 3as , 6r , 7as )- 3a -( 3 , 4 - dimethoxyphenyl ) octahydro - 1h - indol - 6 - yl ] thiourea ( example 19 , 20 mg , 0 . 051 mmol ) and pentanal ( 0 . 25 mmol ), gave the title compound as a colorless oil after preparative hplc purification . 1 h nmr ( 270 mhz , cdcl 3 ): δ ppm 0 . 70 - 0 . 91 ( m , 3h ), 0 . 91 - 1 . 85 ( m , 9h ), 1 . 85 - 2 . 09 ( m , 3h ), 2 . 09 - 2 . 30 ( m , 2h ), 2 . 59 - 2 . 78 ( m , 1h ), 2 . 78 - 2 . 94 ( m , 1h ), 3 . 04 - 3 . 24 ( m , 1h ), 3 . 70 - 3 . 88 ( m , 6h ), 4 . 48 - 4 . 81 ( m , 1h ), 5 . 64 - 5 . 88 ( m , 1h ), 6 . 64 - 6 . 87 ( m , 3h ), 7 . 20 - 7 . 35 ( m , 5h ). ms ( esi +) m / z 496 ( m + 1 ). hrms ( ei ) calc for c 29 h 41 n 3 o 2 s : 495 . 2919 ; found 495 . 2929 . to a solution of tert - butyl ( 3as , 6s , 7as )- 6 -{[( benzylamino ) carbonothioyl ] amino }- 3a -( 3 , 4 - dimethoxyphenyl ) octahydro - 1h - indole - 1 - carboxylate ( example 18 , 10 mg ) in dcm ( 2 ml ) was added trifluoroacetic acid ( 2 ml ) and the resulting solution was stirred at rt during 5 min . the volatiles were evaporated under reduced pressure and the residue was partitioned between etoac ( 5 ml ) and naoh ( aq ., 1m , 2 ml ). the water phase was re - extracted with etoac and the organic phases were washed with saturated aqueous nacl ( 2 ml ), dried ( mgso 4 ) and evaporated to give the title compound as a colourless oil . 1 h nmr ( 500 mhz , cdcl 3 ): δ ppm 1 . 34 - 1 . 46 ( m , 1h ), 1 . 61 - 2 . 08 ( m , 9h ), 2 . 75 - 3 . 04 ( m , 2h ), 3 . 69 - 3 . 79 ( m , 1h ), 3 . 79 - 3 . 95 ( m , 6h ), 4 . 25 - 4 . 79 ( m , 3h ), 6 . 09 - 6 . 61 ( m , 1h ), 6 . 78 - 6 . 85 ( m , 3h ), 7 . 27 - 7 . 39 ( m , 4h ), 8 . 78 - 9 . 64 ( m , 1h ). ms ( esi +): m / z 426 ( m + 1 ). to a solution of mixture of amines , intermediate from example 17 and 18 ( 2 . 2 g , 5 . 84 mmol ) in dichloromethane ( 50 ml ) was added n - butyl thioisocyanate ( 1 . 02 g , 8 . 8 mmol ) and the mixture was stirred orvernight . ps - trisamine ( 2 g ) was added and mixture was filtered and purified by flash chromatography using 20 - 70 % etoac in hexanes . yield : 800 mg of cis - compound . the boc - protected compound from above was deproteced by stirring in dichloromethane ( 10 ml ) and trifluoroacetic acid ( 10 ml ) for 30 min . the mixture was concentrated and redissolved in chloroform . ps - trisamine was added and the mixture filtered . the crude material was used without further purifications . following the general procedure for reductive alkylation of the pyrrolidine moiety , scheme e , using the deprotected amine from above ( 20 mg , 0 . 051 mmol ) and acetaldehyde ( 0 . 25 mmol ), gave the title compound as a colorless oil after preparative hplc purification . 1 h nmr ( 270 mhz , cdcl 3 ): δ ppm 0 . 86 - 0 . 98 ( m , 3h ), 1 . 25 - 0 . 98 1 . 40 ( m , 4h ), 1 . 40 - 1 . 57 ( m , 5h ), 1 . 67 - 1 . 95 ( m , 4h ), 2 . 08 - 2 . 35 ( m , 3h ), 2 . 35 - 2 . 49 ( m , 1h ), 2 . 61 - 2 . 78 ( m , 1h ), 3 . 34 - 3 . 50 ( m , 2h ), 3 . 63 - 3 . 78 ( m , 1h ), 3 . 80 - 3 . 92 ( m , 7h ), 4 . 05 - 4 . 16 ( m , 1h ), 4 . 41 - 4 . 60 ( m , 2h ), 6 . 93 - 7 . 04 ( m , 3h ). ms ( esi +) m / z 420 ( m + 1 ). hrms ( ei ) calc for c 23 h 37 n 3 o 2 s : 419 . 2606 ; found 419 . 2604 . following the general procedure for reductive alkylation of the pyrrolidine moiety , scheme e , using deprotected amine , intermediate from example 40 ( 20 mg , 0 . 051 mmol ) and propanal ( 0 . 25 mmol ), gave the title compound as a colorless oil after preparative hplc purification . 1 h nmr ( 270 mhz , cdcl 3 ): δ ppm 0 . 86 - 1 . 01 ( m , 3h ), 1 . 24 - 1 . 61 ( m , 5h ), 1 . 61 - 2 . 04 ( m , 4h ), 2 . 16 - 2 . 39 ( m , 2h ), 2 . 39 - 2 . 59 ( m , 1h ), 2 . 67 - 2 . 88 ( m , 1h ), 3 . 05 - 3 . 26 ( m , 3h ), 3 . 37 - 3 . 66 ( m , 2h ), 3 . 74 - 4 . 00 ( m , 7h ), 4 . 11 - 4 . 24 ( m , 1h ), 4 . 44 - 4 . 63 ( m , 2h ), 6 . 91 - 7 . 06 ( m , 3h ), 7 . 20 - 7 . 49 ( m , 5h ). ms ( esi +) m / z 434 ( m + 1 ). hrms ( ei ) calc for c 24 h 39 n 3 o 2 s : 433 . 2763 ; found 433 . 2775 . following the general procedure for reductive alkylation of the pyrrolidine moiety , scheme e , using deprotected amine , intermediate from example 40 ( 20 mg , 0 . 051 mmol ) and isobutyraldehyde ( 0 . 25 mmol ), gave the title compound as a colorless after preparative hplc purification . 1 h nmr ( 270 mhz , cdcl 3 ): δ ppm 0 . 85 - 0 . 85 - 1 . 01 ( m , 3h ), 1 . 09 - 1 . 24 ( m , 5h ), 1 . 24 - 1 . 62 ( m , 6h ), 1 . 62 - 2 . 09 ( m , 4h ), 2 . 09 - 2 . 47 ( m , 5h ), 2 . 65 - 2 . 83 ( m , 1h ), 3 . 07 - 3 . 20 ( m , 1h ), 3 . 34 - 3 . 53 ( m , 3h ), 3 . 78 - 3 . 90 ( m , 6h ), 3 . 90 - 4 . 08 ( m , 1h ), 4 . 08 - 4 . 21 ( m , 1h ), 4 . 40 - 4 . 61 ( m , 2h ), 6 . 88 - 7 . 10 ( m , 3h ). ms ( esi +) m / z 448 ( m + 1 ). hrms ( ei ) calc for c 25 h 41 n 3 o 2 s : 447 . 2919 ; found 447 . 2808 . following the general procedure for reductive alkylation of the pyrrolidine moiety , scheme e , using deprotected amine , intermediate from example 40 ( 20 mg , 0 . 051 mmol ) and pentanal ( 0 . 25 mmol ), gave the title compound as a colorless oil after preparative hplc purification . 1 h nmr ( 270 mhz , cdcl 3 ): δ ppm 0 . 85 - 1 . 03 ( m , 6h ), 1 . 22 - 1 . 59 ( m , 10h ), 1 . 61 - 2 . 00 ( m , 7h ), 2 . 10 - 2 . 33 ( m , 2h ), 2 . 33 - 2 . 49 ( m , 1h ), 2 . 64 - 2 . 81 ( m , 1h ), 3 . 08 - 3 . 25 ( m , 1h ), 3 . 35 - 3 . 50 ( m , 2h ), 3 . 50 - 3 . 70 ( m , 1h ), 3 . 74 - 3 . 89 ( m , 7h ), 4 . 06 - 4 . 16 ( m , 1h ), 4 . 38 - 4 . 60 ( m , 1h ), 6 . 92 - 7 . 02 ( m , 3h ). ms ( esi +) m / z 462 ( m + 1 ). hrms ( ei ) calc for c 26 h 43 n 3 o 2 s : 461 . 3076 ; found 461 . 3059 . following the general procedure for reductive alkylation of the pyrrolidine moiety , scheme e , using deprotected amine , intermediate from example 40 ( 20 mg , 0 . 051 mmol ) and phenylacetaldehyde ( 0 . 25 mmol ), gave the title compound as a colorless oil after preparative hplc purification . 1 h nmr ( 270 mhz , cdcl 3 ): δ ppm 0 . 84 - 1 . 00 ( m , 3h ), 1 . 26 - 1 . 58 ( m , 6h ), 1 . 61 - 1 . 82 ( m , 1h ), 1 . 82 - 2 . 03 ( m , 2h ), 2 . 15 - 2 . 37 ( m , 3h ), 2 . 38 - 2 . 54 ( m , 1h ), 2 . 68 - 2 . 87 ( m , 1h ), 3 . 39 - 3 . 65 ( m , 3h ), 3 . 73 - 4 . 00 ( m , 11h ), 4 . 13 - 4 . 22 ( m , 2h ), 4 . 46 - 4 . 61 ( m , 2h ), 6 . 92 - 7 . 04 ( m , 3h ), 7 . 21 - 7 . 48 ( m , 5h ). ms ( esi +) m / z 496 ( m + 1 ). hrms ( ei ) calc for c 29 h 41 n 3 o 2 s : 495 . 2919 ; found 495 . 2914 . following the general procedure for reductive alkylation of the pyrrolidine moiety , scheme e , using deprotected amine , intermediate from example 40 ( 20 mg , 0 . 051 mmol ) and 2 - formyl - cyclopropanecarboxylic acid ethyl ester ( 0 . 25 mmol ), gave the title compound as a colorless oil in after preparative hplc purification . 1 h nmr ( 270 mhz , cdcl 3 ): δ ppm 0 . 82 - 0 . 98 ( m , 3h ), 1 . 05 - 1 . 42 ( m , 9h ), 1 . 42 - 1 . 60 ( m , 2h ), 1 . 66 - 2 . 02 ( m , 5h ), 2 . 12 - 2 . 36 ( m , 2h ), 2 . 36 - 2 . 51 ( m , 1h ), 2 . 59 - 2 . 80 ( m , 1h ), 3 . 14 - 3 . 27 ( m , 2h ), 3 . 47 - 3 . 74 ( m , 3h ), 3 . 74 - 4 . 02 ( m , 7h ), 4 . 05 - 4 . 23 ( m , 3h ), 4 . 36 - 4 . 57 ( m , 2h ), 6 . 89 - 7 . 05 ( m , 3h ). ms ( esi +) m / z 518 ( m + 1 ). hrms ( ei ) calc for c 28 h 43 n 3 o 4 s : 517 . 2974 ; found 517 . 2973 . following the general procedure for reductive alkylation of the pyrrolidine moiety , scheme e , using deprotected amine , intermediate from example 40 ( 20 mg , 0 . 051 mmol ) and furan - 3 - carbaldehyde ( 0 . 25 mmol ), gave the title compound as a colorless oil after preparative hplc purification . 1 h nmr ( 270 mhz , cdcl 3 ): δ ppm 0 . 84 - 1 . 01 ( m , 3h ), 1 . 24 - 1 . 61 ( m , 5h ), 1 . 61 - 2 . 00 ( m , 4h ), 2 . 03 - 2 . 34 ( m , 3h ), 2 . 34 - 2 . 48 ( m , 1h ), 2 . 68 - 2 . 82 ( m , 1h ), 3 . 25 - 3 . 47 ( m , 1h ), 3 . 47 - 3 . 64 ( m , 2h ), 3 . 64 - 3 . 81 ( m , 2h ), 3 . 81 - 3 . 89 ( m , 6h ), 4 . 09 - 4 . 18 ( m , 1h ), 4 . 29 - 4 . 44 ( m , 1h ), 4 . 60 - 4 . 71 ( m , 1h ), 6 . 70 - 6 . 80 ( m , 1h ), 6 . 89 - 7 . 03 ( m , 3h ), 7 . 63 - 7 . 71 ( m , 11h ), 7 . 85 - 7 . 93 ( m , 11h ). ms ( esi +) m / z 472 ( m + 1 ). hrms ( ei ) calc for c 26 h 37 n 3 o 3 s : 471 . 2556 ; found 471 . 2569 . following the general procedure for reductive alkylation of the pyrrolidine moiety , scheme e , using deprotected amine , intermediate from example 40 ( 20 mg , 0 . 051 mmol ) and 1 - methyl - 1h - pyrrole - 2 - carbaldehyde ( 0 . 25 mmol ), gave the title compound as a colorless oil after preparative hplc purification . 1 h nmr ( 270 mhz , cdcl 3 ): δ 0 . 86 - 0 . 97 ( m , 3h ), 1 . 25 - 1 . 42 ( m , 2h ), 1 . 42 - 1 . 57 ( m , 3h ), 1 . 70 - 1 . 98 ( m , 5h ), 2 . 14 - 2 . 32 ( m , 3h ), 2 . 32 - 2 . 56 ( m , 3h ), 2 . 67 - 2 . 82 ( m , 2h ), 3 . 27 - 3 . 47 ( m , 3h ), 3 . 58 - 3 . 73 ( m , 2h ), 3 . 79 - 3 . 89 ( m , 6h ), 4 . 15 - 4 . 22 ( m , 1h ), 4 . 43 - 4 . 54 ( m , 1h ), 6 . 11 - 6 . 16 ( m , 1h ), 6 . 46 - 6 . 51 ( m , 1h ), 6 . 84 - 6 . 89 ( m , 1h ), 6 . 94 - 7 . 01 ( m , 3h ), 7 . 31 - 7 . 31 - 7 . 42 ( m , 1h ). ms ( esi +) m / z 485 ( m + 1 ). hrms ( ei ) calc for c 27 h 40 n 4 o 2 s : 484 . 2872 ; found 484 . 2880 . following the general procedure for reductive alkylation of the pyrrolidine moiety , scheme e , using deprotected amine , intermediate from example 40 ( 20 mg , 0 . 051 mmol ) and 5 - methyl - furan - 2 - carbaldehyde ( 0 . 25 mmol ), gave the title compound as a colorless oil after preparative hplc purification . 1 h nmr ( 270 mhz , cdcl 3 ): δ ppm 0 . 88 - 0 . 99 ( m , 3h ), 1 . 25 - 1 . 58 ( m , 5h ), 1 . 62 - 1 . 98 ( m , 3h ), 2 . 02 - 2 . 18 ( m , 1h ), 2 . 19 - 2 . 32 ( m , 1h ), 2 . 32 - 2 . 38 ( m , 3h ), 2 . 38 - 2 . 57 ( m , 2h ), 3 . 16 - 3 . 49 ( m , 2h ), 3 . 53 - 3 . 69 ( m , 2h ), 3 . 70 - 3 . 81 ( m , 1h ), 3 . 81 - 3 . 90 ( m , 6h ), 4 . 08 - 4 . 19 ( m , 1h ), 4 . 38 - 4 . 52 ( m , 1h ), 4 . 52 - 4 . 71 ( m , 3h ), 6 . 10 - 6 . 18 ( m , 1h ), 6 . 65 - 6 . 72 ( m , 1h ), 6 . 87 - 7 . 03 ( m , 3h ). ms ( esi +) m / z 486 ( m + 1 ). hrms ( ei ) calc for c 27 h 39 n 3 o 3 s : 485 . 2712 ; found 485 . 2721 . following the general procedure for reductive alkylation of the pyrrolidine moiety , scheme e , using deprotected amine , intermediate from example 40 ( 20 mg , 0 . 051 mmol ) and thiophene - 3 - carbaldehyde ( 0 . 25 mmol ), gave the title compound as a colorless oil after preparative hplc purification . 1 h nmr ( 270 mhz , cdcl 3 ): δ ppm 0 . 87 - 1 . 01 ( m , 3h ), 1 . 20 - 1 . 62 ( m , 6h ), 1 . 62 - 2 . 03 ( m , 4h ), 2 . 03 - 2 . 31 ( m , 3h ), 2 . 31 - 2 . 48 ( m , 1h ), 2 . 59 - 2 . 77 ( m , 1h ), 3 . 51 - 3 . 76 ( m , 2h ), 3 . 79 - 3 . 90 ( m , 7h ), 4 . 09 - 4 . 23 ( m , 1h ), 4 . 39 - 4 . 59 ( m , 2h ), 4 . 73 - 4 . 83 ( m , 1h ), 6 . 87 - 7 . 04 ( m , 3h ), 7 . 34 - 7 . 45 ( m , 1h ), 7 . 56 - 7 . 67 ( m , 1h ), 7 . 78 - 7 . 89 ( m , 1h ). ms ( esi +) m / z 488 ( m + 1 ). hrms ( ei ) calc for c 26 h 37 n 3 o 2 s 2 : 487 . 2326 ; found 487 . 2327 . following the general procedure for reductive alkylation of the pyrrolidine moiety , scheme e , using deprotected amine , intermediate from example 40 ( 20 mg , 0 . 051 mmol ) and 5 - methyl - 3h - imidazole - 4 - carbaldehyde ( 0 . 25 mmol ), gave the title compound as a colorless oil after preparative hplc purification . 1 h nmr ( 270 mhz , cdcl 3 ): δ ppm 0 . 86 - 1 . 01 ( m , 3h ), 1 . 23 - 1 . 60 ( m , 6h ), 1 . 66 - 2 . 08 ( m , 3h ), 2 . 12 - 2 . 34 ( m , 2h ), 2 . 34 - 2 . 48 ( m , 1h ), 2 . 48 - 2 . 59 ( m , 4h ), 2 . 60 - 2 . 79 ( m , 1h ), 3 . 16 - 3 . 64 ( m , 3h ), 3 . 68 - 3 . 95 ( m , 8h ), 4 . 19 - 4 . 35 ( m , 1h ), 4 . 41 - 4 . 67 ( m , 2h ), 6 . 90 - 7 . 08 ( m , 3h ), 8 . 81 - 8 . 86 ( m , 1h ). ms ( esi +) m / z 486 ( m + 1 ). hrms ( ei ) calc for c 26 h 39 n 5 o 2 s : 485 . 2824 ; found 485 . 2839 . following the general procedure for reductive alkylation of the pyrrolidine moiety , scheme e , using deprotected amine , intermediate from example 40 ( 20 mg , 0 . 051 mmol ) and 3 - phenylpropanal ( 0 . 25 mmol ), gave the title compound as a colorless oil after preparative hplc purification . 1 h nmr ( 270 mhz , cdcl 3 ): δ ppm 0 . 86 - 1 . 00 ( m , 3h ), 1 . 24 - 1 . 59 ( m , 5h ), 1 . 62 - 1 . 97 ( m , 3h ), 2 . 10 - 2 . 33 ( m , 4h ), 2 . 33 - 2 . 48 ( m , 1h ), 2 . 61 - 2 . 84 ( m , 3h ), 3 . 12 - 3 . 47 ( m , 5h ), 3 . 53 - 3 . 73 ( m , 1h ), 3 . 73 - 3 . 90 ( m , 8h ), 4 . 04 - 4 . 16 ( m , 1h ), 4 . 41 - 4 . 59 ( m , 1h ), 6 . 91 - 7 . 02 ( m , 3h ), 7 . 16 - 7 . 37 ( m , 5h ). ms ( esi +) m / z 510 ( m + 1 ). hrms ( ei ) calc for c 30 h 43 n 3 o 2 s : 509 . 3076 ; found 509 . 3068 . n - benzyl - 1h - pyrazole - 1 - carboximidamide hydrochloride ( 50 mg , 0 . 21 mmol ), diispropylethylamine ( 0 . 03 ml , 0 . 21 mmol ) and ( 3as , 6s , 7as )- 3a -( 3 , 4 - dimethoxyphenyl )- 1 - methyl - octahydro - 1h - indol - 6 - amine , ( comparative example 8 , 60 mg , 0 . 21 mmol ) were mixed in anhydrous dmf ( 1 ml ) and heated at 100 ° c . for 2 hrs . the crude mixture was purified by preparative hplc to give the title compound , 9 mg ( 8 %) n - butyl - 1h - pyrazole - 1 - carboximidamide hydrochloride ( 43 mg , 0 . 21 mmol ), diispropylethylamine ( 0 . 03 ml , 0 . 21 mmol ) and ( 3as , 6s , 7as )- 3a -( 3 , 4 - dimethoxyphenyl )- 1 - methyl - octahydro - 1h - indol - 6 - amine ( comparative example 8 , 60 mg , 0 . 21 mmol ) were mixed in anhydrous dmf ( 1 ml ) and heated at 100 ° c . for 2 hrs . the crude mixture was purified by preparative hplc to give the title compound , 9 mg ( 9 %) hrms ( ei ) calc : 388 . 2838 found : 388 . 2849 . n - pentyl - 1h - pyrazole - 1 - carboximidamide hydrochloride ( 45 mg , 0 . 21 mmol ), diispropylethylamine ( 0 . 03 ml , 0 . 21 mmol ) and ( 3as , 6s , 7as )- 3a -( 3 , 4 - dimethoxyphenyl )- 1 - methyl - octahydro - 1h - indol - 6 - amine ( comparative example 8 , 60 mg , 0 . 21 mmol ) were mixed in anhydrous dmf ( 1 ml ) and heated at 100 ° c . for 2 hrs . the crude mixture was purified by preparative hplc to give the title compound , 9 mg ( 8 %) hrms ( ei ) calc : 402 . 2995 found : 402 . 2991 n - butyl - 1h - pyrazole - 1 - carboximidamide hydrochloride ( 6 mg , 0 . 03 mmol ), diispropylethylamine ( 0 . 01 ml , 0 . 06 mmol ) and ( 3as , 6r , 7as )- 3a -( 3 , 4 - dimethoxyphenyl )- 1 - methyloctahydro - 1h - indol - 6 - amine ( comparative example 7 , 10 mg , 0 . 03 mmol ) were mixed in anhydrous dmf ( 1 ml ) and heated at 100 ° c . for 2 hrs . the crude mixture was purified by preparative hplc to give the title compound , 1 mg ( 7 %) hrms ( ei ) calc : 388 . 2838 found : 388 . 2856 . mesembrine ( 250 mg , 870 μmol ) was dissolved in dcm ( 4 ml ). an aqueous solution of methylamine ( 12 ml of a 50 % solution ) was added , followed by sodium cyanoborohydride ( 250 mg , 3 . 98 mmol ). the mixture was stirred overnight at room temperature and the solvent removed under reduced pressure . the crude product was partitioned between naoh solution ( 25 ml , 3m ) and dcm ( 25 ml ). the aqueous portion was extracted with further dcm ( 2 × 20 ml ), the combined extracts dried ( na 2 so 4 ), and the solvent was removed under reduced pressure . the oily residue was dissolved in dcm ( 5 ml ), and treated with n - butylisothiocyanate ( 115 μl , 110 mg , 960 μmol ). after stirring at room temperature for 16 hours , the solvent was removed and the crude products purified by preparative hplc . ms ( esi +) for c 23 h 37 n 3 o 2 s : m / z 420 . 3 ( m + 1 ). hrms ( ei ) calcd c 23 h 37 n 3 o 2 s : 419 . 2606 , found 419 . 2605 n ′- butyl - n -[( 3as , 6s , 7as )- 3a -( 3 , 4 - dimethoxyphenyl )- 1 - methyloctahydro - 1h - indol - 6 - yl ]- n - methylthiourea ( 40 . 4 mg , 11 %): ms ( esi +) for c 23 h 37 n 3 o 2 s : m / z 420 . 3 ( m + 1 ). hrms ( ei ) calcd c 23 h 37 n 3 o 2 s : 419 . 2606 , found 419 . 2592 compounds were prepared and purified in an analogous method to example 70 and 71 . n ′- benzyl - n -[( 3as , 6r , 7as )- 3a -( 3 , 4 - dimethoxyphenyl )- 1 - methyloctahydro - 1h - indol - 6 - yl ]- n - methylthiourea ( 56 . 3 mg , 14 %): ms ( esi +) for c 26 h 35 n 3 o 2 s : m / z 454 . 2 ( m + 1 ). hrms ( ei ) calcd c 26 h 35 n 3 o 2 s : 453 . 245 , found 454 . 2442 n ′- benzyl - n -[( 3as , 6s , 7as )- 3a -( 3 , 4 - dimethoxyphenyl )- 1 - methyloctahydro - 1h - indol - 6 - yl ]- n - methylthiourea ( 72 . 3 mg , 18 %): ms ( esi +) for c 26 h 35 n 3 o 2 s : m / z 454 . 2 ( m + 1 ). hrms ( ei ) calcd c 26 h 35 n 3 o 2 s : 453 . 245 , found 454 . 2444 . triethylamine ( 0 . 29 ml , 2 . 07 mmol ) was added to a solution of ( 3as , 6s , 7as )- 1 - benzyl - 3a -( 3 , 4 - dimethoxyphenyl ) octahydro - 1h - indol - 6 - amine ( example 6 , 0 . 38 g , 1 . 04 mmol ) in dry ch 2 cl 2 ( 20 ml ). triphosgene ( 0 . 123 g , 0 . 415 mmol ), dissolved in dry ch 2 cl 2 ( 3 ml ), was added to the reaction mixture dropwise . the mixture was stirred at room temperature under n 2 atmosphere for about 30 minutes . during this time the colour changed from light yellow to darker yellow . volatiles were evaporated which gave the crude isocyanate as a yellow solid . ms ( esi +) m / z 393 ( m + h ) + . 1 - methyl - piperazine ( 0 . 164 ml , 1 . 48 mmol ) was added to the crude isocyanate ( 0 . 194 g , 0 . 494 mmol ) dissolved in dry ch 2 cl 2 ( 10 ml ), and the mixture was stirred under n 2 atmosphere for 3 hours . volatiles were evaporated and the crude product was purified by preparative hplc which gave 0 . 64 mg of the title compound as an off - white solid . ms ( esi +) m / z 493 ( m + h ) + . hrms ( ei ) calc for c 29 h 4 o 3 n 4 o 3 : 492 . 3100 found 492 . 3076 . triethylamine ( 62 μl , 0 . 448 mmol ) was added to a solution of ( 3as , 6r , 7as )- 3a -( 3 , 4 - dimethoxyphenyl )- 1 - methyloctahydro - 1h - indol - 6 - amine ( comparative example 7 , 65 mg , 0 . 224 mmol ) dissolved in dry ch 2 cl 2 ( 3 ml ). triphosgene ( 26 . 6 mg , 0 . 0895 mmol ) was dissolved in dry ch 2 cl 2 ( 1 ml ) and added dropwise . the solution was stirred under n 2 in room temperature for 3 h . 1 - methyl - piperazine ( 25 μl , 0 . 224 mmol ) was added and the reaction mixture was stirred at room temperature overnight . volatiles was evaporated and the crude product was purified by preparative hplc which gave 93 mg ( 99 %) of the title compound . 1 h nmr ( 400 mhz , meoh - d4 ) δ ppm 1 . 18 ( s , 3h ), 1 . 21 ( s , 3h ), 1 . 67 - 1 . 75 ( m , 2h ), 2 . 11 ( br s , 2h ), 2 . 26 - 2 . 30 ( br s , 3h ), 2 . 77 - 3 . 35 ( m , 8h ), 3 . 69 ( s , 3h ), 3 . 73 ( s , 3h ), 3 . 78 ( br m , 2h ), 3 . 99 ( br m , 3h ), 6 . 86 ( m , 3h ). ms ( esi +) m / z 417 ( m + h ) + . hrms ( ei ) calc for c 23 h 36 n 4 o 3 : 416 . 2787 found 416 . 2791 . piperazine ( 9 . 5 mg , 0 . 1097 mmol ) was added to the crude solution of isocyanate ( 0 . 1097 mmol ) prepared in comparative example 77 . the mixture was stirred at room temperature under n 2 atmosphere overnight . volatiles were evaporated and the crude product was purified by preparative hplc which gave 5 . 8 mg ( 13 %) of example 76 . ms ( esi +) m / z 403 ( m + h ) + . hrms ( ei ) calc for c 22 h 34 n 4 o 3 : 402 . 2631 found 402 . 2630 . see also under comparative example 77 . triethylamine ( 305 μl , 2 . 19 mmol ) was added to a solution of ( 3as , 6r , 7as )- 3a -( 3 , 4 - dimethoxyphenyl )- 1 - methyloctahydro - 1h - indol - 6 - amine ( comparative example 7 , 318 mg , 1 . 097 mmol ) dissolved in dry ch 2 cl 2 ( 5 ml ). triphosgene ( 130 mg , 0 . 44 mmol ) was dissolved in dry ch 2 cl 2 ( 1 ml ) and added dropwise . the solution was stirred under n 2 in room temperature for 3 h . ms ( esi +) m / z 393 ( m + h ) + . the crude isocyanate was partitioned into several reaction vials , to which the appropriate amine ( see below ) was added ). n -( 2 - aminoethyl ) piperazine ( 14 μl , 0 . 1097 mmol ) was added to the isocyanate ( 0 . 1097 mmol ) solution of comparative example 77 . the mixture was stirred at room temperature under n 2 atmosphere overnight . volatiles were evaporated and the crude product was purified by preparative hplc , which gave 39 mg ( 79 %) of the title compound . ms ( esi +) m / z 446 ( m + h ) + . hrms ( ei ) calc for c 24 h 39 n 5 o 3 : 445 . 3053 found 445 . 3058 . 1 -( 3 - aminopropyl )- 4 - methylpiperazine ( 17 mg , 0 . 1097 mmol ) was added to the isocyanate ( 0 . 1097 mmol ) solution of comparative example 77 . the mixture was stirred at room temperature under n 2 atmosphere overnight . volatiles were evaporated and the crude product was purified by preparative hplc , which gave 22 mg ( 42 %) of the title compound . ms ( esi +) m / z 474 ( m + h ) + . hrms ( ei ) calc for c 26 h 43 n 5 o 3 : 473 . 3366 found 473 . 3364 . 2 -( aminomethyl )- 5 - methylpyrazine ( 21 mg , 0 . 17 mmol ) was dissolved in 1 ml dry ch 2 cl 2 under n 2 . diisopropylamine ( 44 mg , 0 . 34 mmol was added followed by dropwise addition of triphosgene ( 24 mg , 0 . 08 mmol ) in 1 ml of dry ch 2 cl 2 . stirred at room temperature for 2 hrs , and then ( 3as , 6r , 7as )- 3a -( 3 , 4 - dimethoxyphenyl )- 1 - methyloctahydro - 1h - indol - 6 - amine ( comparative example 7 , 50 mg , 0 . 17 mmol ) was added . stirred at room temperature overnight and then concentrated . purification using preparative hplc gave the product as light yellow oil ( 7 . 8 mg , 10 %). 1 hnmr ( 270 mhz , chloroform - d ) ppm 1 . 04 - 1 . 32 ( m , 5h ); 1 . 76 - 1 . 90 ( m , 3h ); 2 . 00 - 2 . 38 ( m , 5h ); 2 . 53 ( s , 3h ); 3 . 46 - 3 . 72 ( m , 1h ); 3 . 87 ( s , 6h ); 4 . 05 - 4 . 20 ( m , 1h ); 4 . 48 ( s , 2h ); 5 . 21 ( w , 1h ); 6 . 70 - 6 . 98 ( m , 2h ); 7 . 30 - 7 . 65 ( m , 1h ); 8 . 36 - 8 . 40 ( m , 2h ); 8 . 47 ( b , 1h ). ms ( esi + ) for c 24 h 33 n 5 o 3 m / z 440 ( m + h + ), hrms found : 439 , 2580 calculated : 439 , 2583 1 - amino - 4 - methylpiperazine ( 13 μl , 0 . 1097 mmol ) was added to the isocyanate ( 0 . 1097 mmol ) solution of comparative example 77 . the mixture was stirred at room temperature under n 2 atmosphere overnight . volatiles were evaporated and the crude product was purified by preparative hplc , which gave 33 mg ( 69 %) of the title compound . ms ( esi +) m / z 432 ( m + h ) + . hrms ( ei ) calc for c 23 h 37 n 5 o 3 : 431 . 2896 found 431 . 2875 . linh 2 ( 7 . 5 g , 328 mmol ) was suspended in dme ( 200 ml ) at ambient temperature and ( 3 , 4 - methylenedioxy ) phenylacetonitrile ( 20 g , 124 mmol ) in dme ( 50 ml ) was added portionwise over 15 min . the mixture was heated at 80 ° c . for 30 min , whereupon its color changed to green , before a solution of 1 - bromo - 2 - chloroethane ( 11 . 3 ml , 136 mmol ) in dme ( 50 ml ) was added over a period of 20 min . during the course of the addition , the green color of the mixture changed to light brown . the mixture was heated at 80 ° c . overnight , or until gc indicated & gt ; 95 % consumption of the starting material . the mixture was cooled on an ice / water bath , and water ( 200 ml ) and et 2 o ( 400 ml ) was then added to destroy the excess of strong base . the mixture was extracted with dcm ( 2 × 100 ml ), and the combined organic extracts were washed with h 2 o ( 100 ml ), dried ( mgso 4 ) and evaporated . the residue was purified by flash chromatography ( silica , 10 - 20 % etoac in n - heptane ) to yield 1 -( 3 , 4 - methylenedioxyphenyl ) cyclopropanecarbonitrile ( 19 . 0 g , 82 %) as a yellowish oil . 1 h nmr ( 270 mhz , cdcl 3 ) δ ppm 1 . 18 - 1 . 32 ( m , 2h ); 1 . 57 - 1 . 66 ( m , 2h ); 5 . 93 ( s , 2h ); 6 . 71 - 6 . 83 ( m , 3h ). 1 -( 3 , 4 - methylenedioxyphenyl ) cyclopropanecarbonitrile ( 19 . 0 g of crude material , 101 mmol ), was dissolved in dry toluene ( 800 ml ) and cooled on an ice / water bath . a solution of dibal ( 1m in toluene , 140 ml , 140 mmol ) was added dropwise via an addition funnel , over a period of 30 min . the resulting mixture was heated at 50 ° c . overnight . the reaction mixture was cooled to 0 ° c . and cautiously transferred , in small portions and with swirling , to a separatory funnel containing ice - cold aq . hcl ( 4m , 0 . 5 l ). the aqueous layer was extracted once with etoac ( 400 ml ) and the combined organic portions were washed with water ( 1 × 300 ml ) and brine ( 1 × 200 ml ), dried ( mgso 4 ) and concentrated to give the aldehyde ( 19 g ) as a yellowish oil , which was used in the subsequent step without further purification . 1 h nmr ( 270 mhz , cdcl 3 ) δ 1 . 32 - 1 . 37 ( m , 2h ); 1 . 49 - 1 . 55 ( m , 2h ); 5 . 95 ( s , 2h ); 6 . 69 - 6 . 83 ( m , 3h ); 9 . 18 ( s , 1h ). to a solution of the aldehyde ( 19 g of crude material , assumed to be 101 mmol ) in dry thf ( 800 ml ) was added benzylamine ( 11 . 9 g , 111 mmol ) and an excess of mgso 4 ( 50 g ) and the resulting mixture was stirred at rt during 24 h . the mixture was filtered and evaporated to give the imine ( 28 g ), which was used in the next step without further purification . 1 h nmr ( 270 mhz , cdcl 3 ) δ 1 . 12 - 1 . 17 ( m , 2h ); 1 . 30 - 1 . 36 ( m , 2h ); 4 . 56 ( s , 2h ); 5 . 93 ( s , 2h ); 6 . 69 - 6 . 89 ( m , 3h ); 7 . 14 - 7 . 40 ( m , 5h ); 7 . 70 ( s , 11h ). to a solution of imine ( 10 g of crude material , assumed to be 53 mmol ) and benzylamine hydrochloride ( 10 g , 68 mmol ) in mecn ( 400 ml ) was added na 2 so 4 ( 20 g ) and but - 3 - en - 2 - one ( 3 . 7 g , 53 mmol ). the mixture was heated at reflux for 5 h and then cooled to rt . the drying agent was filtered off and the filtrate was evaporated to dryness . the residue was partitioned between etoac ( 200 ml ) and saturated aqueous nahco 3 ( 100 ml ), and the aqueous layer was extracted with etoac ( 2 × 100 ml ). the combined organic portions were washed with brine ( 100 ml ), dried ( mgso 4 ) and concentrated to give ( 3as , 7as )- 3a - benzo [ 1 , 3 ] dioxol - 5 - yl - 1 - benzyl - octahydroindol - 6 - one as a colorless oil ( 29 %) after purification by column chromatography ( silica / hexanes : etoac 70 : 30 ). 1 h nmr ( 270 mhz , cdcl 3 ) δ 1 . 85 - 2 . 36 ( m , 6h ); 2 . 40 - 2 . 82 ( m , 3h ); 2 . 87 - 2 . 98 ( m , 1h ); 3 . 10 ( d , 11h , j = 12 . 1 hz ); 3 . 21 - 3 . 26 ( m , 11h ); 4 . 08 ( d , 11h , j = 12 . 1 hz ); 5 . 93 ( s , 2h ); 6 . 71 - 6 . 95 ( m , 3h ); 7 . 17 - 7 . 41 ( m , 5h ). 13 c nmr ( 67 . 9 mhz , cdcl 3 ) 34 . 86 , 36 . 08 , 38 . 45 , 40 . 36 , 47 . 24 , 51 . 46 , 57 . 30 , 68 . 24 , 100 . 88 , 106 . 73 , 107 . 86 , 118 . 48 , 126 . 75 , 128 . 02 , 128 . 57 , 138 . 78 , 141 . 52 , 145 . 63 , 147 . 86 , 210 . 96 . to a solution of ( 3as , 7as )- 3a - benzo [ 1 , 3 ] dioxol - 5 - yl - 1 - benzyl - octahydroindol - 6 - one ( 1 . 5 g , 4 . 30 mmol ) and ammonium formate ( 2 g , 38 mmol ) in meoh ( 100 ml ) was added nabh 3 cn ( 2 g , 32 mmol ) in portions during 5 min . the resulting mixture was stirred at rt for 4 h and then evaporated . the residue was partitioned between etoac ( 100 ml ) and saturated aqueous nahco 3 ( 50 ml ). the aqueous phase was extracted with etoac ( 2 × 50 ml ) and the combined organic fractions were washed with brine ( 50 ml ), dried ( mgso 4 ) and evaporated to give ( 3as , 7as )- 3a - benzo [ 1 , 3 ] dioxol - 5 - yl - 1 - benzyl - octahydro - indol - 6 - ylamine as a colorless oil ( 1 . 3 g , 87 %), which was used in the next step without further purification . 1 h nmr indicated the formation of approximately a 1 : 1 mixture of diastereomers ( at c - 6 ). 1 h nmr ( 270 mhz , cdcl 3 ) δ 0 . 89 - 2 . 42 ( m , 11h ); 2 . 83 - 3 . 30 ( m , 3h ); 4 . 18 ( d , 0 . 5h , j = 13 . 7 hz ); 4 . 30 ( d , 0 . 5h , j = 13 . 0 hz ); 5 . 88 ( s , 2h ); 6 . 64 - 7 . 00 ( m , 3h ); 7 . 10 - 7 . 53 ( m , 5h ). the general procedure for urea / thiourea formation was used , starting from ( 3as , 7as )- 3a - benzo [ 1 , 3 ] dioxol - 5 - yl - 1 - benzyl - octahydro - indol - 6 - ylamine ( 0 . 1 g , 0 . 29 mmol ) and allyl isocyanate ( 34 mg , 0 . 4 mmol ), to give 102 mg ( 74 %) of the mixture of isomers . the isomers were separated by using column chromatography ( silica , chcl 3 / meoh / nh 3 ) and converted to the corresponding hydrochlorides via treatment of dcm solutions with hcl / et 2 o ( sat .) followed by evaporation . first eluted : n - allyl - n ′-[( 3as , 6r , 7as )- 3a -( 1 , 3 - benzodioxol - 5 - yl )- 1 - benzyloctahydro - 1h - indol - 6 - yl ] urea hydrochloride : 23 mg ( 17 %). 1 h nmr ( 500 mhz , cdcl 3 ): δ ppm 1 . 16 - 1 . 34 ( m , 1h ); 1 . 55 - 1 . 68 ( m , 1h ); 1 . 82 ( d , 1h , j = 14 . 1 hz ); 1 . 91 - 2 . 26 ( m , 4h ); 3 . 21 - 3 . 31 ( m , 1h ); 3 . 73 - 4 . 08 ( m , 4h ); 4 . 21 ( dd , 1h , j = 13 . 0 , 4 . 9 hz ); 4 . 45 - 4 . 54 ( m , 1h ); 4 . 56 ( d , 1h , j = 13 . 2 hz ); 5 . 11 ( d , 1h , j = 10 . 6 hz ); 5 . 21 ( dd , 1h , j = 16 . 7 , 4 . 8 hz ); 5 . 44 - 5 . 64 ( br s , 1h ); 5 . 82 - 5 . 95 ( m , 1h , j = 16 . 7 , 10 . 6 , 5 . 0 hz ); 5 . 97 ( s , 2h ); 6 . 59 ( d , 1h , j = 8 . 46 hz ); 6 . 65 ( s , 1h ); 6 . 78 ( d , 1h , j = 8 . 46 hz ); 6 . 68 - 7 . 05 ( br s , 1h ); 7 . 45 - 7 . 53 ( m , 3h ); 7 . 65 ( d , 2h , j = 7 . 06 hz ); 11 . 77 - 12 . 26 ( br s , 1h ). ms ( esi +): m / z 434 ( m + 1 ). hrms ( ei ) calc for c 26 h 31 n 3 o 3 : 433 . 2365 ; found 433 . 2553 . second eluted : n - allyl - n ′-[( 3as , 6s , 7as )- 3a -( 1 , 3 - benzodioxol - 5 - yl )- 1 - benzyloctahydro - 1h - indol - 6 - yl ] urea hydrochloride : greyish gummy solid ; 49 mg ( 36 %). the relative configuration was determined by 1 h nmr spectroscopy ( noesy ). 1 h nmr ( 270 mhz , cdcl 3 ): δ ppm 1 . 23 - 1 . 47 ( m , 2h ); 1 . 54 - 1 . 70 ( m , 1h ); 1 . 77 - 1 . 96 ( m , 2h ); 1 . 98 - 2 . 34 ( m , 2h ); 2 . 35 - 2 . 38 ( m , 1h ); 3 . 04 - 3 . 17 ( m , 1h ); 3 . 20 - 3 . 35 ( m , 2h ), 4 . 21 ( d , 1h , j = 13 . 0 hz ); 4 . 35 - 4 . 50 ( m , 1h ); 4 . 63 - 4 . 80 ( m , 1h ); 4 . 94 - 5 . 23 ( m , 2h ); 5 . 65 - 5 . 88 ( m , 1h ); 5 . 93 ( s , 2h ); 6 . 67 - 6 . 87 ( m , 3h ); 7 . 23 - 7 . 37 ( m , 5h ). ms ( esi +): m / z 434 ( m + 1 ). hrms ( ei ) calc for c 26 h 31 n 3 o 3 : 433 . 2365 ; found 433 . 2358 . the general procedure for urea / thiourea formation was used , starting from from ( 3as , 7as )- 3a - benzo [ 1 , 3 ] dioxol - 5 - yl - 1 - benzyl - octahydro - indol - 6 - ylamine , intermediate from example 86 and 87 ( 0 . 1 g , 0 . 29 mmol ) and ethyl isothiocyanate ( 36 mg , 0 . 4 mmol ), to give 111 mg ( 81 %) of the mixture of isomers . the isomers were separated by using column chromatography ( silica , chcl 3 / meoh / nh 3 ) and converted to the corresponding hydrochlorides via treatment of dcm solutions with hcl / et 2 o ( sat .) followed by evaporation . n -[( 3as , 6r , 7as )- 3a -( 1 , 3 - benzodioxol - 5 - yl )- 1 - benzyloctahydro - 1h - indol - 6 - yl ]- n ′- ethylthiourea hydrochloride ( slower elute ): greyish gummy solid ; 30 mg ( 20 %). the relative configuration was determined by 1 h nmr spectroscopy ( noesy ). 1 h nmr ( 270 mhz , cdcl 3 ): δ ppm 0 . 81 - 0 . 96 ( m , 1h ); 1 . 03 ( t , 3h , j = 7 . 05 hz ); 1 . 10 - 1 . 52 ( m , 2h ); 1 . 55 - 1 . 75 ( m , 2h ); 1 . 75 - 2 . 10 ( m , 5h ); 2 . 18 ( d , 1h , j = 15 . 6 hz ); 2 . 56 - 2 . 71 ( m , 1h ); 2 . 87 - 3 . 54 ( m , 3h ); 4 . 03 - 4 . 50 ( m , 1h ); 5 . 12 - 5 . 26 ( br s , 1h ); 5 . 94 ( s , 2h ); 6 . 69 - 6 . 89 ( m , 3h ); 7 . 23 - 7 . 44 ( m , 5h ). ms ( esi +): m / z 438 ( m + 1 ). hrms ( ei ) calc for c 25 h 31 n 3 o 2 s : 437 . 2137 ; found 437 . 2151 . faster elute : n -[( 3as , 6s , 7as )- 3a -( 1 , 3 - benzodioxol - 5 - yl )- 1 - benzyloctahydro - 1h - indol - 6 - yl ]- n ′- ethylthiourea hydrochloride : greyish gummy solid ; 58 mg ( 40 %). the relative configuration was determined by 1 h nmr spectroscopy ( noesy ). 1 h nmr ( 270 mhz , cdcl 3 ): δ ppm 1 . 03 - 1 . 16 ( m , 4h ); 1 . 16 - 1 . 32 ( m , 3h ); 1 . 36 - 1 . 52 ( m , 1h ); 1 . 60 - 1 . 93 ( m , 3h ); 1 . 94 - 2 . 06 ( m , 1h ); 2 . 10 - 2 . 48 ( m , 2h ); 2 . 95 - 3 . 13 ( m , 2h ); 3 . 16 - 3 . 38 ( m , 2h ); 4 . 15 - 4 . 28 ( m , 1h ); 5 . 27 - 5 . 51 ( br s , 1h ); 5 . 94 ( s , 2h ); 6 . 69 - 6 . 89 ( m , 3h ); 7 . 27 - 7 . 48 ( m , 5h ). ms ( esi +) m / z 438 ( m + 1 ). hrms ( ei ) calc for c 25 h 31 n 3 o 2 s : 437 . 2137 ; found 437 . 2124 . the general procedure for urea / thiourea formation was used , starting from ( 3as , 7as )- 3a - benzo [ 1 , 3 ] dioxol - 5 - yl - 1 - benzyl - octahydro - indol - 6 - ylamine , intermediate from example 86 and 87 ( 0 . 9 g , 2 . 57 mmol ) and benzyl isothiocyanate ( 500 mg , 3 . 3 mmol ), to give 960 mg ( 65 %) of the mixture of isomers . the isomers were separated by using column chromatography ( silica , chcl 3 / meoh / nh 3 ) and converted to the corresponding hydrochlorides via treatment of dcm solutions with hcl / et 2 o ( sat .) followed by evaporation . n -[( 3as , 6s , 7as )- 3a -( 1 , 3 - benzodioxol - 5 - yl )- 1 - benzyloctahydro - 1h - indol - 6 - yl ]- n ′- benzylthiourea hydrochloride ( faster eluting ): colorless gummy solid ; 500 mg ( 17 %). the relative configuration was determined by 1 h nmr spectroscopy ( noesy ). 1 h nmr ( 270 mhz , cdcl 3 ) δ ppm 0 . 81 - 0 . 96 ( m , 1h ); 1 . 16 - 1 . 47 ( m , 2h ); 1 . 53 - 2 . 48 ( m , 10h ); 2 . 92 - 3 . 26 ( m , 2h ); 4 . 09 - 4 . 23 ( m , 2h ); 4 . 53 - 4 . 63 ( br s , 1h ); 5 . 94 ( s , 2h ); 6 . 71 - 6 . 90 ( m , 3h ); 7 . 15 - 7 . 42 ( m , 10h ). ms ( esi +) m / z 500 ( m + 1 ). hrms ( ei ) calc for c 30 h 33 n 3 o 2 s : 499 . 2293 ; found : 499 . 2277 the general procedure for urea / thiourea formation was used , starting from ( 3as , 7as )- 3a - benzo [ 1 , 3 ] dioxol - 5 - yl - 1 - benzyl - octahydro - indol - 6 - ylamine , intermediate from example 86 and 87 ( 0 . 1 g , 0 . 29 mmol ) and n - butyl isothiocyanate ( 46 mg , 0 . 4 mmol ), to give 95 mg ( 68 %) of the mixture of isomers . the isomers were separated by using column chromatography ( silica , chcl 3 / meoh / nh 3 ) and converted to the corresponding hydrochlorides via treatment of dcm solutions with hcl / et 2 o ( sat .) followed by evaporation . the title compound ( slower elute ): greyish gummy solid ; 48 mg ( 33 %). the relative configuration was determined by 1 h nmr spectroscopy ( noesy ). 1 h nmr ( 270 mhz , cdcl 3 ) δ ppm 0 . 86 ( t , 3h , j = 7 . 3 hz ); 1 . 06 - 2 . 06 ( m , 12h ); 2 . 18 ( d , 1h , j = 16 . 0 hz ); 2 . 55 - 2 . 70 ( m , 1h ); 2 . 85 - 3 . 33 ( m , 3h ); 3 . 45 ( d , 1h , j = 13 . 3 hz ); 4 . 04 - 4 . 14 ( m , 1h ); 4 . 58 - 4 . 75 ( br s , 1h ); 5 . 19 - 5 . 33 ( br s , 1h ); 5 . 93 ( s , 2h ); 6 . 70 - 6 . 87 ( m , 3h ); 7 . 23 - 7 . 45 ( m , 5h ) 8 . 43 - 8 . 59 ( br s , 1h ). ms ( esi +): m / z 466 ( m + 1 ). hrms ( ei ) calc for c 27 h 35 n 3 o 2 s : 465 . 2450 ; found 465 . 2435 . the general procedure for urea / thiourea formation was used , starting from ( 3as , 7as )- 3a - benzo [ 1 , 3 ] dioxol - 5 - yl - 1 - benzyl - octahydro - indol - 6 - ylamine , intermediate from example 86 and 87 ( 0 . 1 g , 0 . 29 mmol ) and t - butyl isothiocyanate ( 46 mg , 0 . 4 mmol ), to give 103 mg ( 74 %) of the mixture of isomers . the isomers were separated by using column chromatography ( silica , chcl 3 / meoh / nh 3 ) and converted to the corresponding hydrochlorides via treatment of dcm solutions with hcl / et 2 o ( sat .) followed by evaporation . the title compound ( slower elute ): colorless gummy solid ; 19 mg ( 14 %). the relative configuration was determined by 1 h nmr spectroscopy ( noesy ). 1 h nmr ( 270 mhz , cdcl 3 ) δ ppm 0 . 80 - 0 . 97 ( m , 1h ); 1 . 16 - 1 . 47 ( m , 11h ); 1 . 62 - 2 . 32 ( m , 7h ); 2 . 57 ( d , 11h , j = 14 . 0 hz ); 2 . 88 - 3 . 20 ( m , 2h ); 4 . 59 - 4 . 80 ( br s , 1h ); 5 . 29 ( d , 1h , j = 9 . 0 hz ); 5 . 78 - 5 . 90 ( br s , 1h ); 5 . 93 ( s , 2h ); 6 . 72 - 6 . 91 ( m , 3h ); 7 . 16 - 7 . 49 ( m , 5h ). ms ( esi +): m / z 466 ( m + 1 ). hrms ( ei ) calc for c 27 h 35 n 3 o 2 s : 465 . 2450 ; found 465 . 2448 . the general procedure for urea / thiourea formation was used , starting from ( 3as , 7as )- 3a - benzo [ 1 , 3 ] dioxol - 5 - yl - 1 - benzyl - octahydro - indol - 6 - ylamine , intermediate from example 86 and 87 ( 0 . 1 g , 0 . 29 mmol ) and t - butyl isothiocyanate ( 46 mg , 0 . 4 mmol ), to give 103 mg ( 74 %) of the mixture of isomers . the isomers were separated by using column chromatography ( silica , chcl 3 / meoh / nh 3 ) and converted to the corresponding hydrochlorides via treatment of dcm solutions with hcl / et 2 o ( sat .) followed by evaporation . example 91 ( faster elute ): colorless gummy solid ; 48 mg ( 34 %). the relative configuration was determined by 1 h nmr spectroscopy ( noesy ). 1 h nmr ( 270 mhz , cdcl 3 ) δ ppm 1 . 20 - 1 . 32 ( m , 1h ); 1 . 42 ( s , 9h ); 1 . 58 - 1 . 73 ( m , 1h ); 1 . 49 - 2 . 05 ( m , 6h ); 2 . 24 ( d , 1h , j = 16 . 5 hz ); 2 . 62 - 2 . 79 ( m , 1h ); 3 . 10 - 3 . 23 ( m , 2h ); 3 . 70 ( d , 1h , j = 13 . 8 hz ); 4 . 00 ( d , 11h , j = 13 . 8 hz ); 5 . 55 - 5 . 65 ( br s , 1h ); 5 . 93 ( s , 2h ); 6 . 68 - 6 . 80 ( m , 3h ); 7 . 25 - 7 . 40 ( m , 5h ); 7 . 94 - 8 . 11 ( br s , 1h ). ms ( esi +): m / z 466 ( m + 1 ). hrms ( ei ) calc for c 27 h 35 n 3 o 2 s : 465 . 2450 ; found 465 . 2450 . the general procedure for urea / thiourea formation was used , starting from ( 3as , 7as )- 3a - benzo [ 1 , 3 ] dioxol - 5 - yl - 1 - benzyl - octahydro - indol - 6 - ylamine , intermediate from example 86 and 87 ( 0 . 1 g , 0 . 29 mmol ) and n - butyl isothiocyanate ( 46 mg , 0 . 4 mmol ), to give 95 mg ( 68 %) of the mixture of isomers . the isomers were separated by using column chromatography ( silica , chcl 3 / meoh / nh 3 ) and converted to the corresponding hydrochlorides via treatment of dcm solutions with hcl / et 2 o ( sat .) followed by evaporation . the title compound ( faster eluting ): colorless gummy solid ; 30 mg ( 21 %). the relative configuration was determined by 1 h nmr spectroscopy ( noesy ). 1 h nmr ( 270 mhz , cdcl 3 ) δ ppm 0 . 82 - 0 . 96 ( m , 4h ); 1 . 14 - 2 . 52 ( m , 14h ); 2 . 96 - 3 . 36 ( m , 4h ); 4 . 20 - 4 . 31 ( m , 2h ); 5 . 32 - 5 . 61 ( br s , 1h ); 5 . 93 ( s , 2h ); 6 . 71 - 6 . 90 ( m , 3h ); 7 . 24 - 7 . 50 ( m , 5h ). ms ( esi +) m / z 466 ( m + 1 ). hrms ( ei ) calc for c 27 h 35 n 3 o 2 s : 465 . 2450 ; found 465 . 2451 . the general procedure for urea / thiourea was used , starting from ( 3as , 7as *)- 3a - benzo [ 1 , 3 ] dioxol - 5 - yl - 1 - benzyl - octahydro - indol - 6 - ylamine , intermediate from example 86 and 87 ( 0 . 9 g , 2 . 57 mmol ) and benzyl isothiocyanate ( 500 mg , 3 . 3 mmol ), to give 960 mg ( 71 %) of a mixture of isomers . the isomers were separated by using column chromatography ( silica , chcl 3 / meoh / nh 3 ) and converted to the corresponding hydrochlorides via treatment of dcm solutions with hcl / et 2 o ( sat .) followed by evaporation . the title compound ( slower elute ): colorless gummy solid ; 350 mg ( 12 %). the relative configuration was determined by 1 h nmr spectroscopy ( noesy ). 1 h nmr ( 270 mhz , cdcl 3 ) δ ppm 0 . 79 - 0 . 93 ( m , 1h ); 1 . 14 - 2 . 60 ( m , 8h ); 3 . 00 - 3 . 15 ( m , 1h ); 3 . 38 ( 1h , d , j = 13 . 3 hz ); 3 . 95 - 4 . 78 ( m , 4h ); 4 . 64 - 4 . 75 ( br s , 1h ); 5 . 53 - 5 . 56 ( br s , 1h ); 5 . 94 ( s , 2h ); 6 . 68 - 6 . 86 ( m , 3h ); 7 . 16 - 7 . 41 ( m , 10h ). ms ( esi +) m / z 500 ( m + 1 ). hrms ( ei ) calc for c 30 h 33 n 3 o 2 s : 499 . 2293 ; found : 499 . 2283 the active ingredient 1 is mixed with ingredients 2 , 3 , 4 and 5 for about 10 minutes . the magnesium stearate is then added , and the resultant mixture is mixed for about 5 minutes and compressed into tablet form with or without film - coating . the ability of a compound of the invention to bind or act at the mch1r receptor can be determined using in vitro and in vivo assays known in the art . the biological activity of compounds prepared in the examples was tested using different tests . the compounds according to the invention were evaluated for their binding to the human mch1r receptor by the following method : compounds : mch peptide was purchased from phoenix pharmaceuticals . ( phe 13 , [ 125 i ] tyr 19 melanine - concentrating hormone ( human , mouse , rat ) ([ 125 i ]- mch ) was obtained from nen life science products . inc . boston , mass . wheat germ agglutinine spa beads ( rpnq 0001 ) were obtained from amersham - pharmacia biotech . all other reagents used are of highest purity from different resources available . protein kits , micro bca ™ protein assay reagent kit ( cat no . 23235 ) were purchased from piece , rockford , ill ., usa . plastic wares : cell culture flasks , dishes were from decton dickinson labware , n . j ., usa . scintillation plate , white clear bottom were from wallac , finland . cho - k1 cells expressing hmch1 receptor were purchased from euroscreen . cho - k1 hmchri ( euroscreen , brussels , belgium , # es - 370 - c ) were cultivated in nutrient mixture ham &# 39 ; s f - 12 with glutamax i ( gibco - brl # 31765 - 027 ) supplemented with 10 % heat - inactivated foetal calf serum ( fcs , gibco - brl # 10108 - 165 ) and 400 μg / ml geniticin ( gibco - brl # 1140 - 0359 ). the cells were sub - cultivated twice weekly with split ratio = 1 : 20 - 1 : 30 . for membrane preparation the cells were cultured in 500 mm 2 dishes and the cells were harvested when 90 % confluent . when the cells reached more than 90 % confluence , dishes ( 500 cm 2 ) were rinsed twice with 20 ml pbs ( ca 2 + and mg 2 + free ). buffer a , which contains tris . hcl ( 15 ), mgcl 2 . 6h 2 o ( 2 ), edta ( 0 . 3 ), egta ( 1 ) in mm with ph 7 . 5 , 25 ml was added and cells were suspended using a window scraper . the cells were collected in 50 ml falcon tube pre - cooled on ice and then centrifuged for 3 minutes at 1500 g at 4 ° c . the supernatant was discarded and the cells were suspended again with buffer a . the cells were homogenized using a polytron homogenizer at setting 4 for 4 times for 30 seconds with 1 minute pause between the cycles . the homogenized preparation was centrifuged at 40 , 000 g ( 18500 rpm with ss - 34 , no . 5 rotor in sorvall centrifuge , rc5c , dupont ) for 25 minutes at 4 ° c . the pellets were washed once with buffer a and centrifuged again under the same conditions . the pellets were suspended with buffer b , which contains tris . hcl ( 7 . 5 ), mgcl 2 . 6h 2 o ( 12 . 5 ), edta ( 0 . 3 ), egta ( 1 ), sucrose ( 25 ) in mm with ph 7 . 5 , and gently homogenized for several times with a glass homogenizer . the membrane preparation was aliquoted into eppendorf tubes , 1 ml / tube and frozen at − 70 ° c . the protein determination was done as described in the instruction provided with pierce protein assay kit ( peirce micro bca protein assay reagent kit , no 23235 , pierce , usa ). briefly , the piece working reagent components a , b and c were mixed in the ratio 25 : 24 : 1 . bsa ( no . 23209 , pierce , usa ) provided with the kits was used as standard , which the concentration in the curve is 1 , 2 , 4 , 6 , 8 , 12 , 16 and 24 μl / ml . the samples from membrane preparation were diluted for 50 , 100 , 200 , 400 times . the standards or the samples 150 μl and the working reagent 150 μl were mixed in each well in a costa 96 well microtiter plate and incubated at 37 ° c . for 2 hours . the plate was cooled down to room temperature and read at 595 nm with a microplate reader from molecular devices , usa . the wga beads were re - constructed with reaction buffer , which contains tris ( 50 ), mgcl 2 ( 5 ), edta ( 2 . 5 ) in mm with ph adjusted to 7 . 4 , to 40 mg / ml as a stock suspension . to link the membrane with the bead , the beads and the membrane will be pre - incubated with for 30 minutes at room temperature with gentle shaking . the suspension of the beads was centrifuged at 3400 rpm for 2 minutes using centrifuge . the supernatant was discarded and the beads were re - suspended with binding buffer , hepes ( 25 mm ), mgcl 2 ( 5 mm ), cacl 2 ( 1 mm ), bsa ( 0 . 5 %) with peptidase inhibitors ( 1 μg / ml ) leupeptin , aprotinin and pepstatin , ph 7 . 4 . since appropriated beads and membrane construction is needed for spa , the ratio of beads and membrane in link were tested and it will be indicated where the experiments are described . the radio labeled [ 125 i ]- mch was diluted with cold mch in ratio 1 : 3 . in kd determination , the concentrations of labeled peptide were 3 nm with 1 : 2 series dilution for 11 samples . the amount of the beads was 0 . 25 mg / well . the results were calculated using excel program and the curves were drawn using a program graphpad prism . for screening of the substances the amount of the beads used was 0 . 25 mg / well and the amount of the membrane protein was 4 μg / well 0 . 2 nm of labeled mch was used . the total volume was 200 μl , which contained 50 μl [ 125 i ]- mch , 100 μl substances and 50 μl beads . the plate was gently shaken for 30 minute and incubated overnight . the samples were counted using microbeta counter ( wallac trilux 1450 micro beta counter , wallac , finland ) for 2 minutes and the results were calculated by using the computer program activity base . the equilibrium time of the binding was investigated at room temperature , 30 and 37 ° c . the equilibrium time was about 30 minutes at 37 ° c . but the binding was lower compared with that at room temperature and 30 ° c . the equilibrium time was about 2 hours at 30 ° c . while it took about 4 hours to reach stable binding at room temperature . thus , room temperature was chosen since it is easy condition for experiments . the [ 125 i ]- mch binding to hmch r1 was further characterized by determination of kd values . the kd values are same , 0 . 19 nm , as reported by chambers j , ames r s , bergsma d , muir a , fitzgerald l r , hervieu g , dytko g m , foley j j , martin j , liu w s , park j , ellis c , ganguly s , konchar s , cluderay j , leslie r , wilson s , sarau h m . melanin - concentrating hormone is the cognate ligand for the orphan g - protein - coupled receptor slc - 1 . nature 1999 jul . 15 ; 400 ( 6741 ): 261 - 5 . in all displacement experiments , 0 . 2 nm [ 125 i ]- mch was used for total binding and 300 nm mch used as non - specific binding . the background is low and the signal is good . the z ′ factor was 0 . 83 which is considered very good for screening . kd values from present study were consistent with that from macdonald d , murgolo n , zhang r , durkin j p , yao x , strader c d , graziano m p . molecular characterization of the melanin - concentrating hormone / receptor complex : identification of critical residues involved in binding and activation . mol pharmacol 2000 july ; 58 ( 1 ): 217 - 25 but were slightly different from that 1 . 2 nm from hervieu g j , cluderay j e , harrison d , meakin j , maycox p , nasir s , leslie r a , the distribution of the mrna and protein products of the melanin - concentrating hormone ( mch ) receptor gene , slc - 1 , in the central nervous system of the rat . eur j neurosci 2000 april ; 12 ( 4 ): 1194 - 216 . the reason for this is unknown but might be caused by different clones of the cells . the calculation of the k i values for the inhibitors was performed by use of activity base . the k i value is calculated from ic 50 and the k m value is calculated using . the cheng prushoff equation ( with reversible inhibition that follows the michaelis - menten equation ): k i = ic 50 ( 1 +[ s ]/ k m ) [ cheng , y . c . ; prushoff , w . h . biochem . pharmacol . 1973 , 22 , 3099 - 3108 ]. the ic 50 is measured experimentally in an assay wherein the decrease of the turnover of cortisone to cortisol is dependent on the inhibition potential of each substance . the compounds of formula ( i ) exhibit the ic 50 values for the mch1r receptor in the range from 10 nm to 10 μm . illustrative of the invention , the following ki values have been determined in the assay ( see table 1 ):	2
first , briefly in overview , the present invention is directed to a novel proxy asset system operated by a system proprietor responsible for implementing and managing a group of proxy assets . the system proprietor is linked to various ancillary information sources and outlets , via communications links including dedicated server lines , the internet or similar . thus , the system is accessible to brokers or outside investors , in a limited and pre - defined way . the proxy asset system is implemented by a proxy asset data processor and a programmed controlled criterion for operation , with this criterion well understood by participants . the proxy asset data processor includes a proxy asset account manager and a proxy asset dividend generator . in addition , the proxy asset system preferably includes a trading , issuance and redemption system that receives and stores customer orders to buy and sell , including market orders , limit orders and possibly other varieties of order , and executes these orders by trading existing proxy asset shares or issuing or redeeming proxy asset shares in complete sets , here defined , as needed . the stored programming implements a cash account formula , that defines the balances in the cash accounts and a dividend payout formula for each proxy asset , to be discussed here below . the pooled resources for all cash accounts within the system are invested in some assets , such as money market instruments , by an investment manager , or separate firm external to the system , characterized herein as the bank . the bank reports to the system proprietor the value of the pooled resources , and the system proprietor tracks the separate cash accounts for the proxy assets , which are claims on the pooled funds in the bank . the underlying criteria for account processing are publically distributed to insure complete knowledge by participants . transfers are made among cash accounts within the proxy asset system . the illustrative examples here present a single proxy asset system , recognizing that there could be more than one such system , each operating at different institutions run by different system proprietors . turning to an exemplary proxy asset system implementing , at a minimum , two proxy assets for real estate in a given city for a given base year . these two proxy assets are referred to as an up proxy asset and a down proxy asset , one share of each forming what will be called a complete set ( see also below ). the first proxy asset , the up proxy asset , has a cash account balance per share that is adjusted by the system proprietor according to a cash account formula that specifies that it contains , at regular intervals ( e . g ., quarterly ), a balance proportional to the real estate price index for the given base year for that city , and investors (&# 34 ; shareholders &# 34 ;) in that proxy asset receive a regular dividend according to a dividend payout formula that specifies a dividend payout equal to a constant , predetermined , payout rate times the balance in the cash account corresponding to that share and subject to an upper limit . the second proxy asset , the down proxy asset has cash account balance per share that is set , according to its cash account formula , to equal the combined balances in the cash accounts for both up and down proxy asset per share minus the balance in the up proxy asset cash account per share . its dividend payout formula defines a dividend equal to the payout rate times the balance in that account , so long as that balance is positive , and not exceeding an upper bound . the system is defined so that all dividends payouts are always feasible : the sum of the dividend payout formulas for an up share and a down share is always less than the combined balances per share in the two accounts in the bank , by construction . accordingly , buying shares in the up proxy asset corresponds to investing in the illiquid real estate itself ; the proxy asset is , however , liquid . moreover , shares in the up proxy asset have the look and feel of an ordinary investment , since they confer on the investor a claim on the cash account which &# 34 ; backs &# 34 ; the proxy asset , thereby encouraging a receptive market psychology for these assets . investments in the down proxy asset are less clearly analogous to existing investments . one might call a share in one of them analogous to a portfolio consisting of a short position in real estate and also the margin account balance for that short position . by this interpretation , if the assets are created when the index is at 100 , we may say that the margin account has an initial margin of 200 %, rather than the 150 % required by the federal reserve regulations for conventional short positions , the higher initial margin allowing for a reasonably well - functioning hedging vehicle without margin calls . if the index drifts far from 100 , then the proxy asset system creates new up and down proxy assets with an index that is 100 in a newer base year , issuing both up and down proxy assets at 100 . investors may then redeem their original proxy assets and purchase those with the newer base year . since the down proxy asset does not involve margin calls at all and resembles an asset , it is better to regard it as a fundamentally new investment vehicle that makes it much easier for participants to hedge their risks . in accordance with pre - defined logic and controlling system instructions , the system proprietor has two primary functions . the first is to create the proxy assets and distribute shares in these assets , like the up - down proxy assets described in the example above , in a way that allows free commercial access and payment of a market price for the proxy assets , and to allow redemption of shares . the second aspect involves , as seen in the example above , the management of a cash account for each proxy asset that is linked to the cash accounts of other proxy assets in the system and so that the changes in the value of the underlying assets are translated into changes in cash account balances and ultimately into dividends for distribution to the owners of the proxy asset shares . a third function , a trading , issuance and redemption system , is optionally integrated as a feature of the system . as in the example above , each proxy asset within the proxy asset system has a prespecified cash account formula that defines how much is in its cash account per share at each point of time . those proxy assets whose cash account formulas sum identically to the combined cash values per share in the cash accounts corresponding to all the proxy assets in the set will be called a complete set of proxy assets . as long as all proxy assets are part of complete sets of proxy assets , then it is always possible for all proxy assets to be created such that the proxy asset data processor can always adhere to the cash account formulas defining the proxy assets &# 39 ; s balances without running out of cash . ( there may also be restrictions on the kinds of complete sets for which share redemptions or new share issues will be generated .) proxy assets will be issued and redeemed by the proxy asset data processor only in complete sets , so that the cash account balances defined by the cash account formula and the dividends can always be paid in accordance with the cash account formula . we can clarify what we have said above about issuance and redemption in mathematical terms . let us call v t the total value of all pooled cash accounts for a given base year in the bank at time t . call s , the number of shares of all proxy assets in the system . thus , the value per share , averaging over the entire system with that base year is v t / s t , though individual proxy assets within the system will have different values . the proxy asset data processor allows free issuance of new shares and redemption of existing shares at any time t at prices so as not to disturb v t / s t . thus , when a packet of new shares is issued at time t , if there are s t shares in the packet , the total value of the packet must be v t s / s t , so that after issuance there will be s t + s t shares and the total value after the issuance will be v t + v t s t / s t . it follows that the value per share after issuance will be ( v t + v t s t / s t )/( s t + s t ) which equals v t / s t , the same as it was before the issuance . note that in general the individual shares will nol be issued or redeemed at price v t / s t , nor will the underlying cash value accounts for each share contain that amount . the cash account formula for each proxy asset specifies how much its cash account contains per share , at regular intervals such as quarterly , in terms of some measure of value or income of underlying proxy assets , as well as in terms of v t / s t , and possibly other economic variables such as inflation or interest rates . a complete set is a set of n shares of proxy assets such that the sum of cash account formulas for the cash accounts per share equals nv t / s t . thus , so long as the shares comprise a complete set according to the formula definitions , they can be issued or redeemed together without affecting v t / s t . the dividend payout formula for each proxy asset specifies how much is paid out as a dividend per share each time period to owners of that proxy asset as a function of the balance in that proxy asset &# 39 ; s cash account per share , and possibly as a function of other data , such as interest rates and the rate of inflation , and possibly as a function of the balances in cash accounts that belong to the same complete set . the dividend payout formula must be specified so that dividend payments are always feasible given the balances in the cash accounts . there is an important reason for issuing and redeeming shares only in such a way that the value per share , averaging over the entire system , is unaffected . the reason is that the cash account balances of individuals will thus be protected from being influenced by the decisions of other investors to issue or redeem . the cash account for each proxy asset has several purposes . first , all proxy asset holders receive dividends equal to the amounts in their asset value account at the dividend definition date times a payout factor defined by the dividend payout formula , generally , the same payout factor applied to all proxy assets managed by a single proxy asset system . second , the account balance is used by the system to determine whether offers to buy or sell can be settled by issuance of new proxy assets or redemption of old proxy assets . third , the account balance is provided to customers as information relevant to their evaluation of the proxy assets ; the cash account balance may be referred to as the cash value of the investment , and thus lends substance to the otherwise amorphous securities . two illustrative techniques depict the issuance and redemption of proxy assets . the first technique involves issuing complete sets of proxy assets to brokers by conventional underwriting methods , just as new shares in corporations are issued today . brokers who buy the complete sets will then have the burden of selling off the elements of the complete sets to clients as best they can , leaving the problem of finding customers for the elements of the complete sets to the brokers . moreover , brokers can redeem the complete sets of proxy assets by purchasing on the market the complete sets , and submitting these back to the system proprietor . the second technique provides for an integrated trading , issuance , and redemption system implemented by the system proprietor , ( possibly with the participation of an existing electronic trading system ) that solves the problem of finding complete sets for the brokers , and also allows trading of existing shares . if the proxy asset shares are traded on the trading system described here , participants in the system , ( e . g ., brokers and possibly individuals ), can place orders to buy or sell proxy assets in the form of either a market order ( to buy or sell at any price ) or a limit order ( to buy at a price at or below a given price or to sell at a price at or above a given price ), and possibly other kinds of orders . the system will manage the buy or sell orders partly as do other existing trading systems today : in the case of limit orders , it will search for matches , sell limit orders that are at or below buy limit orders for single proxy assets , and clear them . it will also execute buy or sell orders in another way . whenever a set of unmatched buy orders can be found that constitutes a complete set of proxy assets , at combined prices equal to or above the combined values of the cash accounts of the proxy assets , then the orders will be executed by creating a new complete set of proxy assets and crediting the proceeds of the sale ( minus some commission ) into the cash accounts in amounts corresponding to the balances currently in the accounts . whenever a set of sell orders can be found that constitutes a complete set of proxy assets , at combined prices at or below the combined values of the cash accounts of the proxy assets , then the orders will be executed by redeeming a complete set of proxy assets , and transferring the balances ( minus some commission ) in the cash accounts in amounts corresponding to the balances currently in the accounts to the sellers . when such complete sets are discovered among buy or sell orders , it means that it is feasible to execute the order by issuance and / or redemption without having any effect on the system proprietors &# 39 ; ability to keep asset balances at their values specified by the cash account formula , and the execution will then be done automatically . the trading , issuance , and redemption system is preferably fully automated and electronic , though it is possible that elements of the system may need to be done manually , given possible regulatory or other issues . please see u . s . pat . no . 4 , 674 , 044 to kalmus , et al ., relating to automated trading techniques , the contents of which are incorporated by reference . it is possible in some implementations of the trading , issuance , and redemption system that the system proprietor is not the only exchange , or even the primary exchange , on which the existing proxy assets are traded . trades on the system may be limited to issuance and redemption , or limited to certain times , such as once a month . system constraints will reflect federal and state regulations , taxation issues , and issues raised by existing securities exchanges . a separate aspect involves the creation of proxy asset bundles , groupings of proxy assets that may be traded as a bundle even if the individual components do not trade individually . under this approach , the system implements the dismantling of the proxy asset bundles under select circumstances . the bundling and dismantling will be illustrated below . applying the above structure to a real estate example , two proxy assets are established for each city ( and associated base year ) to be managed by the system : one ( the up proxy asset for a long position in real estate in that city , and the other ( the down proxy asset ) for a short , or reciprocal position , in the city . we shall suppose that when the proxy assets for this base year were first issued in that base year , the home price index was scaled so that the index equaled 100 then , and the initial cash accounts for both the up proxy asset and the down proxy assets originally contained $ 100 . the cash account formula for the up proxy asset at quarterly intervals after that is just the price index : up cash account balance per share end of quarter = home price index . the cash account formula for the down proxy asset cash account balance per share , that determines its cash account balance at time t , is : down cash account balance per share end of quarter = 2 × total account balances per share - home price index . ( in terms of the mathematics shown above , the up proxy asset cash account balance at the end of quarter t equals the home price index at time t , i t , and the down proxy asset cash account balance equals 2v t / s t - i t .) transfers between the accounts are made each quarter to assure that at the end of each quarter these cash account formulas are satisfied . thus , if the index is 100 in the base year and is now 120 , ( reflecting an increase in real estate prices since the base year ) then the underlying account for each up security has $ 120 in it . the cash account balance for one share of the down security is just the combined investment value of the balances in a pair of up and down securities in that city minus the index . the combined investment value in the up and down cash accounts was $ 200 on the base date , when the index was 100 by definition , and today is the accumulated investment value ( in the money market fund where cash account balances are invested ) since the base date of $ 200 , after paying out dividends according to the dividend payout formula . thus , for example , if the combined value in the up and the down cash accounts per share is now $ 205 , then when the index is at 120 , the down account has $ 85 corresponding to each down security . to support issuance - redemption and trade execution , the proxy asset data processor searches over the buy and sell orders to find a complete set whose total prices exceed the total value of a set . since a complete set consists of one up proxy asset share and one down proxy asset share , then whenever an offer to buy an up proxy asset share at price p 1 and a down proxy asset share at price p 2 are found such that p 1 + p 2 ≧ 2v t / s t , then both orders are executed and from the proceeds of the combined sale the proxy asset data processor allocates an amount equal to the value corresponding to one share in the up cash account to that account , and an amount equal to the value corresponding to one share in the down cash account to that account . thus , after this issuance of new shares , each share has the same cash account balance as before , and there are now more shares outstanding . when offers to sell the shares are found at prices such that p t + p 2 ≦ 2v t / s t , then the shares are redeemed and the proceeds of the sale deducted from the cash accounts in proportion to the amounts already in these accounts . moreover , when an offer to buy one up proxy asset share at price p 1 and an offer to sell one up proxy asset share at price p 2 is found by the proxy asset data processor so that p 1 ≦ p 2 , then the order is executed without issuance or redemption , merely by selling an existing share . the same occurs for offers to buy and sell down proxy assets . in the above examples , we have neglected , for illustrative purposes only , the commission charged for the sales and also the profit accruing from these trades . the dividend payout formula for both up and down proxy assets in this example is given by : dividend per share = r ×( amount in own cash account per share ) if positive and if amount in own cash account is less than the combined value in the two accounts = r ×( combined amount in the two accounts ) if amount in own cash account is greater than the combined value where r is a payout rate defined by the proxy asset system rules ; it could be a fixed number such as 2 % per annum , corresponding to an estimate of the long - term real interest rate on money market accounts . ( it must of course be less than 100 % so that the dividend payout is always feasible , but presumably it will be much less .) the down proxy asset &# 39 ; s cash account could have a negative value in it , in which case no dividend will be paid to its shareholders . in this case , the up proxy asset &# 39 ; s cash account would have more than the total cash in the two accounts , in which case the dividend paid for the up proxy asset per share would just be the payout rate , r , times the total cash in the two accounts per share . the market price of the down proxy asset will still be positive , since there is always the possibility that the index will drop enough to bring its balance to a positive number again . note that the market price of the up proxy asset will tend to the index , so long as the index does not differ too far from 100 . in this case , investing in the up proxy asset will be a proxy for investing in the real estate itself . so long as the unobserved dividends ( in the form of housing services ) on the actual real estate are approximated by the dividend payout formula payout rate , then the owner of the proxy asset will be receiving the same dividends as would be received by investing in the real estate itself . so long as the proxy asset price stays close to the price index for the real estate , then investing in the proxy asset will also tend to produce essentially the same capital gains and losses as investing in real estate . however , investing in the proxy asset will not produce the identical capital gains and losses because the proxy asset market will be more liquid , allowing investors to take better opportunity of predictable movements in index values . the down proxy asset will be extremely useful to homeowners wishing to hedge the risks of their investment in their own home . as is well known , many recent declines in real estate markets have caused homeowners to lose the real equity in their homes . a single decision of a homeowner to put part of his or her investments in a down proxy asset for the city will then effectively hedge the homeowner indefinitely against such price risk . because the down proxy asset has such a simple form , and is easily understood , it is easy for people to do this . the system will provide continuous information about the balance in the cash account , and thus investors will have the satisfaction of knowing that their accounts are &# 34 ; backed &# 34 ; by some real assets . they will also know that if certain predefined circumstances pertain ( such as termination of the system ), they will automatically receive the balance in their cash account , further strengthening their impression that their investment has substantive value , even though such circumstances are so defined as to be unlikely for the foreseeable future . bundling is applied to our up - down proxy assets to facilitate the marketing of the assets . for example it is possible that in each city there is a demand for the down asset for that city , corresponding to the natural hedging demand for people of that city , but little or no demand for the individual up assets of individual cities , as investors all want to be diversified . the system creates and market down assets for each of the cities , but the corresponding up proxy assets for each city is bundled for distribution as a single global up proxy asset which is a portfolio of the up proxy assets for all cities . these up assets could then later be taken apart , under defined circumstances . the initial down proxy assets could also be for individual zip codes or even census tracts , thereby facilitating very accurate hedging for individual homeowners , and the up proxy assets marketed could be only highly aggregated as of the corresponding individual up proxy assets . a second form of proxy asset , continuing the real estate example , is labeled here swap proxy assets . investors wishing to swap out of the risk in their own city can buy an asset that is short their own city and long some other city . with such assets , they cannot adjust their overall real estate exposure ( as they could with up - down proxy assets ) but they can diversify their real estate exposure across cities ( horizontal hedging ). adjusting the exposure to their own city can be a useful portfolio management device , since many investors are not overinvested in real estate per se but are overexposed to real estate in one region . with between - city - swap proxy assets , this kind of hedging of one &# 39 ; s risk and diversification into other cities can have the appearance of buying ordinary shares in other cities . buying the proxy asset is like buying a share in the other city and selling exposure in a first city . if we begin the system for n cities , then there are n2 - n ordered pairs of cities , and there will be one swap proxy asset for each such pair . for the ijth pair , then the cash account formula for the cash account for one share of swap proxy asset ij is : cash account balance per share for swap proxy asset ij = average cash account value per share + 2 ( index i - index j ) and we will have for the jith pair a swap proxy asset whose cash account formula is : cash account balance per share for swap proxy asset ij = average cash account value per share + 2 ( index j - index i ) note that the average cash account value per share is the total balance in all cash accounts in the system per share , denoted v t / s t above . in this example the swap proxy assets are more levered than in the previous up - down example , in that the indices are multiplied by two . ( another multiplier , other than two , could of course be used , to create a different amount of leverage ; the number given is just for illustration .) the prices of the swap proxy assets will not have the simple interpretation of the price of the up proxy asset of the previous example , but the assets will have the offsetting advantage that they offer effective means of diversifying risk . one way of defining the complete sets for the purpose of issuance and redemption is that all pairs of investments , one share in ij and one in ji , are complete sets . in this case , we can use the same dividend rule as was defined in the previous example , the example of up - down proxy assets . there are other possible ways to define complete sets . a complete set could consist of a share in ij a share jk and a share in ki proxy assets . these sets are circles of assets . if we defined such alternative complete sets , then we may wish to alter the dividend payout formula so that , in the case where some balances are negative , so that some swap proxy assets are paying no dividend , the dividends on the remaining swap proxy assets still sum to the payout rate times the combined balances . fig1 shows an illustration of the kinds of closed paths ( complete sets ) that the swap system processor identifies among the orders to buy and sell shares . the first set , set a , is just a san francisco - denver swap proxy asset paired with a denver - san francisco swap proxy asset . the second set , set b , is a complicated closed path involving three cities and three swap proxy assets . the proxy asset data processor applies these more complicated definitions of complete sets and searches the data to find opportunities to issue , redeem , and allow trade of proxy assets , a process much more complicated than was the case with the up - down proxy assets . for example , setting the average cash account balance in the system ( v t / s t ) at $ 105 . 50 dollars per share , suppose that three book windows on the trading display screen are as shown : ______________________________________bid quantity offer quantity______________________________________boston / chicago base 1998010111015 100 11015 5011014 50 11016 5011013 50 11018 1001999 / 03 / 02 10 : 53chicago / seattle base 19980101 8593 50 8594 501999 / 03 / 02 10 : 53seattle / boston base 1998010112042 50 12043 50 12045 50 12046 1001999 / 03 / 02 10 : 53______________________________________ the proxy asset system and processor would discover that a bid for 50 boston - chicago shares at $ 110 . 15 matches with the offer to sell 50 boston - chicago shares , and so this trade would automatically be executed , and the match shown on the hypothetical window above would not persist for more than an instant . to execute these orders , there is no need for issuance or redemption . the computer will also discover that there is a bid for boston - chicago for another 50 shares at $ 110 . 15 , a bid for 50 chicago - seattle shares at $ 85 . 93 , and a bid for 50 seattle - boston shares for $ 120 . 42 , and that the sum of these prices is $ 316 . 50 , or three times the average cash account value per share ( 3 v t / s t ), and so it automatically fills these orders by issuing the new proxy assets , and allocating the proceeds from the sale into the respective cash accounts in proportion to amounts already there . once again , these orders would not persist on the book window for more than an instant . note that in interfacing with an electronic trading system , such as the globex or other system , there would ideally be some minor modifications in the electronic trading system . for an obvious example , traders would probably appreciate the ability to maintain more than one book window on the screen at a time , because of the interaction of orders within complete sets . for another example , traders who have asked the trading system to alert them when the price has hit a specific level may also want to be alerted in case any combination of orders for other proxy assets within the same compete set would suggest an opportunity to obtain the specified price by issuance or redemption at the specified price . it would be natural for our system to do this alerting , since such an operation would combine naturally with the enterprise of searching for complete sets among the orders . these swap proxy assets will work very well for those investors who already hold both real estate and other investments , but whose real estate investment is largely accounted for by their own homes , which are too concentrated in each city . for example , a person who owns a $ 400 , 000 home in los angeles and is worried about possible poor performance of real estate in los angeles relative to new york can invest $ 100 , 000 in proxy asset shares like those described just above that is short los angeles and long new york , and thereby create a situation in which he or she is effectively invested in the los angeles market only in the amount of $ 200 , 000 , and is effectively invested in the new york market in the amount of $ 200 , 000 , thereby diversifying risks equally between the two cities . the person could also invest $ 40 , 000 in each of four swaps , a new - york - los angeles swap proxy asset , a miami - los angeles swap proxy asset , and a chicago - los - angeles swap proxy asset , a denver - los angeles swap proxy asset , thereby diversifying from an exclusive los angeles real estate position to a real estate position that is equally diversified across five cities . the swap proxy assets are optionally bundled together and sold only as a group ( called here a proxy asset bundle ). for example , if there is a lot of demand among residents of each city to swap their city real estate index for an average of all other cities , thereby effecting a diversified investment , then the only assets that need be marketed are the bundles of swaps that respond positively to a single city . under certain conditions , these proxy asset bundles will provide the underlying swaps to the public which then may be disassembled later if demand appears for the individual components of the bundles . if there is a lot of demand among investors to invest in how well each city &# 39 ; s real estate index will perform relative to all of the others combined , the relevant assets are the proxy asset bundles of swap proxy assets of each city versus all of the others . in this case , complete sets with only two elements would not exist ; complete sets would require representation of all cities . such structures permit investors to go long the chosen city while requiring no one to hedge any city . such a structure could be of value if the demand for hedging is minimal . a third form of proxy asset is labeled here as multi - asset pools . this arrangement has no down securities , only up securities , the up securities for a given illiquid asset functioning also as down securities for the others together . here , n proxy assets , each , corresponding to an index i at , a = 1 , . . . , n , at time t , swaps the one index against the remaining n - 1 indices . a complete set is one of each of the n proxy assets . the cash account function that defines the balance per share after transfer in cash account a at time t may be given by : ## equ1 ## for example , if n = 2 , then the assets are analogous to swaps between pairs of assets , as with the swap proxy assets described above . for another example , if n = 5 , there could be five proxy assets , one for the real estate of each of the five largest cities of the country . note that this formula satisfies the adding - up constraint ; the total value of all accounts after transfers still equals the total amount in all accounts before transfer . another cash account formula that would define the balance in the cash account a at time t with a nonlinear formula : ## equ2 ## where the weights w a , a = 1 , . . . , n correspond to the relative amounts outstanding of the various assets . ( for example , cities with more people in them would get more weight .) a complete set is again one of each of the n proxy assets . with such a formula , the individual proxy asset cash accounts would never hit zero . note that this formula also satisfies the adding - up constraint ; the total value of all cash accounts after transfers still equals the total amount in all cash accounts before transfer . the amounts in the various accounts would always correspond to the values in the various illiquid assets . thus , there will be less of a need to issue securities with a new base year as time goes on . this multi - asset pooling proxy asset security will tend to be less volatile than the one defined by the linear formula . with the foregoing description in mind , attention is now directed to fig2 providing a schematic block diagram of the proxy asset account manager in the up - down proxy asset version . in this exemplary arrangement , two proxy assets are created , and the two constitute a complete set . in particular , the system proprietor issues shares of up proxy asset ( a ) ( block 10 ), following orders placed in the system on behalf of investors by conventional brokerage arrangements ( block 40 ). similarly , the system proprietor also issues , at block 20 , the down proxy assets ( b ), also following orders placed in the system by brokers on behalf of investors . importantly , the shares must be issued only in complete sets , which in this example means that the number of a proxy assets issued must equal the number of b proxy assets issued . receipts from the sale of both the up and the down securities are pooled by the system proprietor in the bank and then the individual cash accounts credited with shares of this pool , block 30 , in proportions to the amounts per share already in these accounts . as provided above , it can be recognized that no actual underlying illiquid asset has been identified or purchased by the system proprietor , and accordingly , no meaningful transaction expenses have been incurred . the system operates to provide a proxy to real estate . the up proxy assets are marketed with a set of defining parameters including a link to an established index , and the cash account , acct a tied to these account balance would grow in proportion with the index . in a reciprocal manner , the down proxy asset &# 39 ; s cash account balance would drop in value in proportion to an increase in the real estate index value . this is practically implemented by having actual capital taken from acct b and deposited in acct a in correspondence with the changing index value , as shown at 70 . acct a would grow and acct b would shrink by a like amount . as the underlying index is capable of both growth and retraction , fig2 depicts capital flows in both directions . in accordance with stored program logic , the system receives input on adjusted account balances and determines a dividend payment , w corresponding to this new balance . an inverted relation is found between the index and the dividend stream of acct b , linked to the down securities . as real estate markets appreciate , funds in acct b are transferred out , leaving less capital for dividend generation w &# 39 ;, and thus a reduced dividend for the holders of the down proxy assets b . these proxy assets , however , should remain in demand at some price , because of the cash account value and because of their usefulness as a hedging vehicle against a drop in real estate values . implementation of the foregoing features is best accomplished via digital computer utilizing a uniquely defined controlling logic , wherein the computer system includes an integrated network between and among the various participants in the proxy asset security . this is depicted generally in fig3 wherein a block diagram highlights the components of a computer system useful for implementing these assets . the computer system is of conventional design , having a central processor ( cpu ) block 100 linked to a main database , db ( i ), block 110 . the main database includes archival data on the various securities , and allows proper manipulation of the underlying parameters in accordance with system logic . the database structure is outlined in detail in the database structure section below . the logic controlling system operation is stored in discrete memory block 120 . one aspect of the foregoing system involves the input of price or income indices in the underlying illiquid asset markets , recording price movements and / or income changes necessary to implement changes in proxy asset accounts . accordingly , the system includes commlink , block 140 , to a network for proper controlled communication to various institutions and investors involved in the proxy asset . these participants have separate workstations , 150 located at remote locations , but in communication with the system . it is expected that the bank and the price and income index provider ( s ) as well as the brokers handling trades with individuals , and possibly also individuals themselves , will each communicate with the system proprietor . the actual hardware configuration used is not particularly critical , as long as the processing power is adequate in terms of memory , accounts , periods of updating indexed values , the number of proxy assets and their respective cash account formulas and dividend payout formulas , and order execution , redemption and issuance . a network of pcs with a windows nt operating system is expected to give acceptable performance . oracle based database engines allow substantial account coverage and expansion . the controlling logic will invariably use a language and compiler to match that on the cpu 100 . these selections will be set according to per se well known conventions in the software community . an alternative configuration would involve , instead of the 150 workstation linked by windows nt , an internet web site that allows trade directly over the internet . use of the system could still be restricted to brokers , if that is the objective , by suitable password procedures . table 1 below shows an exemplary arrangement of the database for the proxy asset data processor . this table shows the records and fields that will be necessary for proper management under this embodiment . table 1______________________________________database structure______________________________________format : recordsfieldsshareholder information : customer or client i . d . number : name or firm : address : proxy asset or bundle id numbers : current numbers of shares or bundles owned in each : transaction id numbers : transaction information : transaction id number : proxy asset or bundle id number : buyer id number : seller id number : exchange , issuance or redemption : date and time : number of shares or bundles : price per share or bundle : complete set id number : buy and sell orders : order number : customer id number : buy order or sell order : proxy asset id number or bundle id number : if market order : numbers of shares or bundlesif limit order : price and numbers of shares or bundlesif stop order : price and numbers of shares or bundlesorder date and time : order expiration date and time : e . g . fill order until 1 : 00 pm 1 / 5 / 98pooled cash account information : total investable assets held for cash accounts ( in bank ) ( v . sub . t ): total number of shares outstanding in entire system ( s . sub . t ): average cash account balance per share in system ( v . sub . t / s . sub . t ): complete sets : set number : proxy asset or bundle id numbers in set : index information : index id number : update frequency : e . g . quarterlydate of last update : market description : e . g . single family homes in metro los angelesprice or income index : e . g . pricedate : e . g . first quarter 1980index level : e . g . 100 . 00cash account formula : cash account formula id number : proxy asset type : swap , up or down , etc . : cash account formula : e . g ., a ) for up cash account = index ( index id number ) b ) for down cash account = 2 × v . sub . t / s . sub . t - index ( index idnumber ) c ) for swap cash account = v . sub . t / s . sub . t + 2 × ( a index - bindex )( index id numbers ) dividend payout formula : dividend payout formula id number : proxy asset type : swap , up or down , etc . : dividend payout dates : dividend payout formula : e . g ., dividend paid per share = 0 . 02 × ( cash account balance ) proxy asset balance change information : proxy asset cash balance change formula id : proxy asset id number : index id number : cash account formula id number : cash balance change frequency : e . g . quarterlynext cash balance change date : historical cash balance changes : historical cash balance change id numberhistorical cash balance change date : historical cash balance before change amount : historical cash balance change amount : historical cash balance after change amount : proxy asset definition : proxy asset id number : proxy asset type : swap , up or down : initial cash per share : e . g . $ 100 . 00base date : e . g . january 10 , 1998current number of shares outstanding : e . g . 500 , 000current cash account balance per share : e . g . $ 100dividend frequency : next dividend due : e . g . january 10 , 1998cash account formula id number : dividend payout formula id number : next cash balance change due : e . g . january 10 , 1998cash account number : next interest deposit due : issuance id : redemption id : proxy asset bundle definition : proxy asset bundle id : proxy asset id numbers : number of shares of each proxy asset in bundle : issuance history : proxy asset or bundle id number : complete set id number : issuance id number : issuance date : number of shares : issuance amount per share : redemption history : proxy asset or bundle id number : complete set id number : redemption id number : redemption date : number of shares : redemption amount per share : ______________________________________ may be a multiple field there are three primary functions of the logic command instructions . the first is to allow controlled creation of proxy assets , by defining new proxy assets from scratch , by bundling existing proxy assets together , by debundling existing proxy asset bundles , or by doing combinations of the above . the second is to transfer balances among cash accounts so that the cash account formula is satisfied by the balances . the third is to define and allocate dividends on the proxy assets . in each case , the critical controlling data must be stored in the properly configured database . the first of these three functions is important , as success in risk management requires identifying the appropriate risk categories , categories that may be changing all the time . for example , investor demand for proxy assets in real estate may suddenly shift to a small configuration of neighborhoods that might be represented by a combination of zip - code or census - tract real estate price indices . we want to have a system in which the creation of new proxy assets such as these can be done as automatically as possible , by a trained representative of the system proprietor operating the proxy asset data processor , or even , possibly , by broker clients themselves . if the cost of creating new proxy assets is made very low , then we might expect to see many more such proxy assets created . the first function is accomplished in accordance with the logic flow chart depicted in fig4 . logic conceptually begins at start block 200 and continues to block 210 wherein the proxy asset under consideration ast ( i ) is entered by the system user . by ast ( i ) we mean , for the real estate example , a definition of the geographical area , identification of real estate price index , base year , cash account formula , and dividend payout formula . since users will find it difficult to specify these , the system may provide tools , such as maps showing locations of zip codes or census tracts , and some summary statistics about the price indices for each of these . the system first tests whether the entered proxy asset definition ast ( i ) is new and cannot be approximated by existing proxy assets , by an identical proxy asset already defined , by proxy assets with a slightly different base year , by new bundles of existing proxy assets , by components of existing proxy asset bundles , or by combinations thereof . in an initial run , test 220 , the system searches over the existing proxy assets , the possibilities for new proxy asset bundles from existing proxy assets , components of existing proxy asset bundles , and displays the characteristics of the proxy assets that may be thus generated , including information about the cash account balance that would be implied for the proxy asset under consideration . possibly , some combination or division of proxy assets with a slightly different base year may be close enough to the proposed proxy asset . if the user signals that the entered proxy asset is not sufficiently new , if one of the possibilities put forward by the data processor is satisfactory , logic branches to block 230 and the existing records are pulled from the database for the already extant proxy asset or proxy asset bundles , with logic shifted to a separate subroutine . a positive response to test 220 branches logic to block 250 wherein the parameters of the new proxy asset are entered into the system , and the parameters of the remaining elements of the complete set specified . in the case of simple up - down proxy assets , as illustrated in the figure , the complete set can be automatically defined by the system , providing a definition of the proxy asset pair ( ast -- par ( i )), both elements of which must now be created . at this point , it must be decided whether the new proxy asset pair should be defined in terms of a single index or whether the pair should be defined as a proxy asset bundle in terms of a cluster of component indices . if the former , the system branches to block 290 . if the latter , the system branches to block 270 , where the bundle is defined , possibly by entering new indices into the system , and updating the database , block 280 . at test 310 , the system queries about a default cycle for the asset adjustment period . a negative response to this allows custom entry of a controlling cycle , cyc ( i ) setting the time interval between adjustments for the accounts and dividends for the up - down proxy assets . the more common response to test 310 defaults the controlling interval to a system stored value , blocks 320 - 330 . this completes the first portion of the processing with logic shifted to the next sequence , block 350 . creation of the underlying cash accounts and associated computer files and displays forming the foundation for the up - down proxy asset pair is accomplished by the logic control commands shown in fig5 . beginning at start block 1400 , logic first enables the entry of the pending proxy asset pair , ast -- par ( i ) block 1410 . the system checks whether this is a new proxy asset pair at test 1420 . if new , logic continues to block 1440 , wherein the cash account balance per share ast -- bal ( i ) is entered for both elements of the pair . these balances provide the financial backbone of the proxy assets . implementation is made at blocks 1450 - 1460 setting up the two corresponding accounts accta ( i ) and acctb ( i ): operation allows the entry of custom account parameters (&# 34 ; yes &# 34 ; to test 1470 -- and entry at block 1490 ) or entry of pre - selected default values , block 1480 . as previously described , the system includes a communication link between various participants and governing institutions . a book window is created , block 1500 , for traders on the trading system , indicating , initially , the defined cash account balances per share for both proxy assets in the pair , even though no shares yet exist . orders may now be placed by customers , and these will appear on the book window . to create the first proxy asset share , since no shares yet exist , the trading system must first identify a complete set within the orders whose value equals ( or exceeds ) the combined cash account balances per share . thereafter , the system can fill orders both by exchanging existing shares and by finding complete sets among orders . when a complete set is first created , the bank or similar repository of capital in account form , must be notified with wire transfer of funds and automatic structuring of accounts particularized in advance , in response to the order . during routine operation of the proxy asset system , the system proprietor will be directly responsible for rebalancing the accounts ( maintained by the bank in pooled form only ) within complete sets with the changing indices governing the accounts . returning to fig5 after the database is updated with the current ( and new ) ast ( i ) information , logic queries on the next ast value ( i + 1 ) at test 1530 ; if another batch is ready , logic continues to the beginning and the process is repeated for the next in series . day to day operation of the system requires analysis of a variety of time - varying inputs and selective calculation of a number of distinct variables to allow operation of the proxy asset . in fig6 several of these operations and routine procedures are depicted as examples of system processing , recognizing that many other variables are tracked in like fashion . beginning with block 1600 , logic in fig6 first pulls the current date , date ( j ), and enters this into the process , block 1610 . the current proxy asset pair file is recalled , block 1620 read , which includes the current asset balances updated for interest earned by the bank . the periodic date is compared to the present date to determine if the current date is an event date for adjusting the proxy asset accounts . a positive response to test 1630 reflects the match of dates and need to update the accounts ; accordingly logic continues to block 1640 and the system recalls the current index value for the tracked asset , idx ( i , j ). in this context , the counter variable j tracks the cycle -- and thus absolute and relative time periods . continuing with fig6 the system applies the cash account formula to the down proxy asset , block 1650 , making the balance per share equal the combined balances per share in the two accounts before the transfer minus the index , and applies the cash account formula to the up proxy asset , block 1660 , making the balance per share just equal to the index . note that the combined balances of the two accounts is unchanged by this transfer , so the transfer is always feasible , even though the down proxy asset cash account balance may be negative . then the foregoing calculations are applied to calculate the appropriate dividend level per share for each proxy asset pair , using the dividend payout formula . in block 1670 , the system queries whether the balance in the down proxy asset is negative . if no , the system proceeds to blocks 1680 and 1690 , where each account is given a dividend at the rate dr ( i ). if yes , then the system branches to block 1700 , where the up proxy asset is defined a dividend equal to dr ( i ) times the combined values in the two accounts , and block 1710 , where the down proxy asset is given a dividend of 0 . these values are then stored in the main database , db ( x ) at block 1720 , and the entire process repeated for the next proxy asset under management by incrementing index variable i , block 1730 . as previously described , the system includes a communications link between various participants and governing institutions . this includes a bank or similar repository of capital in account form , with wire transfer of funds and automatic structuring of accounts particularized in advance , and individual brokers or even individual investors who might place orders directly with the system . during routine operation of the proxy management system , the bank will be directly responsible for investing the pooled balances of the cash accounts , while the proxy asset system will be responsible for maintaining the cash accounts for the individual proxy assets , thereby in effect dividing up the balance in the bank among proxy asset shareholders . execution of orders , by issuance and redemption or matching and clearing of buy and sell orders , for the proxy assets is accomplished by the logic and control commands detailed in fig7 and 8 . fig7 shows the proxy asset order processor . beginning at start block 400 in fig7 the order entry subroutine is detailed . orders are received at block 410 from investors or brokers via workstations 150 ( fig3 ) or internet link . orders may consist of market orders ( to buy or sell a specific number of a specific proxy asset at any price ) or limit orders ( to buy a specific number of proxy assets at or below a certain price , or to sell a specific number of proxy assets at or above a certain price , bids and offers , hits and takes ), or possibly other kinds of orders . these buy and sell orders are stored , at block 420 , in a pending order list for each proxy asset in what is essentially equivalent to a book window in the trading system . they may be arranged , in effect , in the book window with the highest bid at the top of one column , and the highest offer at the top of another column , with prices in descending value below these . with reference to fig8 the proxy asset trading , issuance and redemption system begins at block 500 . in a subroutine beginning at block 510 , the pending order lists corresponding to each proxy asset are individually accessed and searched . at block 520 , if a buy order for a proxy asset is matched with an identical sell order for that proxy asset , those shares are traded at block 530 without the issuance or redemption of any additional shares , those orders removed from the pending order list and processing returns to block 520 to search for additional matching orders . when no additional matches are present in the pending order list for the current proxy asset , the no path from block 520 is followed and processing loops , asset in the system . when all matching orders in the system have been processed , logic extends to block 550 , whereupon the buy orders for all proxy assets in the system are together searched for a complete set or closed path . as discussed in example i , a complete set is just an up - down pair . in example ii above , closed paths may consist of reciprocal swap proxy assets ( e . g ., ij and ji ) or a more complicated set , such as an ij swap , a jk swap , and a ki swap ( or any other path beginning and ending on the same asset ). the combination of the proxy assets in the path have a total value as discussed in example ii . the sum of the buy orders in the path must equal or exceed this value . if so , test block 560 branches to a processing routine , beginning at block 570 , for issuing new shares of these proxy assets , updating the cash accounts of the respective proxy assets in the proportion to amounts already there , then deletes these buy orders from the pending order list , before returning to loop 550 to search for additional closed paths . alternately , if the sum of the buy orders in the identified path do not meet the total value of the path , the path identified in block 550 is rejected at test 560 and different path combinations are searched . when no additional complete sets ( closed paths ) are located in subroutine 550 , processing continues to a subroutine beginning at block 600 , searching for closed paths of sell orders in the pending order lists of all proxy assets in the system . the sum of the sell orders is compared to the total value of the proxy assets in the identified path at block 610 . if greater , the orders are executed beginning with block 620 by redeeming existing shares of these proxy assets , updating the cash accounts to reflect the redeemed proxy assets and deleting the sell orders from the pending order list . processing then continues to exhaust all possible closed paths . when all closed paths are identified , the subroutine ends at block 630 , or alternately , the abilities of one skilled in the art of programming may allow the system proprietor to implement the subroutines instead beginning at blocks 510 , 550 and 600 as separate , and / or concurrent subroutines . the execution of the buy and sell orders may also be connected to procedures whereby trade is suspended in unusual market situations , akin to the circuit breakers of organized exchanges . the execution of the buy and sell orders may be limited to certain classes of customers , such as registered broker dealers . the execution of the buy and sell orders may also be connected to a market surveillance system , like those at existing exchanges , to check for attempts at market manipulation or other illegal trading practices . fig9 is a relational block diagram depicting the proxy asset bundle manager . in this diagram , four proxy assets , proxy assets a , b , c , and d are shown for illustration . in this example , only proxy asset d is sold directly to the public . proxy assets a , b , and c are bundled together as shown , and the bundle is sold to the public . since the cash accounts for proxy assets a , b , and c are already in place , and their cash account formulas and dividend payout formulas already defined , people will have some idea of the effects of taking this proxy asset bundle apart at a later date . knowing that the proxy asset bundle is decomposable later may facilitate its marketing to the public today . table 2 below shows an outline of the functions of the proxy asset data processor . the table gives an outline of the basic steps that this data processor must handle , on a continuing or daily basis , and the steps that are undertaken only on a less frequent basis . table 2______________________________________functions of proxy asset data processor______________________________________1 . functions ordered by system proprietoradd index data ( run manually ) load new index into index record databasefill in other fields of index recordupdate interest payment ( run daily ) for each proxy asset : is interest deposit due today ? if yes : adjust current cash balance with interest paymentfill in next interest deposit duepay dividends ( run daily ) for each proxy asset : interest deposit run for today ? if yes : dividend payment due today ? if yes : use dividend payout formula to calculate dividendpay dividend , adjust current cash account balancefill in next dividend payment dueupdate indices ( run daily ) for each indexdate for an index update ? if yes : receive index update into index recordupdate cash account balances using cash account formulas ( run daily ) index , interest and dividend update performed already for today ? if yesfor each proxy asset : look up cash balance change formula and necessary indicescalculate cash account balances changeis transfer between accounts due today ? if yes : make transfers among cash accounts according tocash account formuladefine new swap proxy asset ( run manually ) select the two indices to be used , rescale to 100 on base dateselect formula typefill in base date and initial cash per sharefill in cash account formulafill in dividend payout formulamake list of all complete setsdefine new up / down proxy asset pair ( run manually ) select the index to be used , rescale to 100 on base dateselect formula typefor both up and down proxy asset : fill in base date and initial cash per share ( same for both ) fill in cash account formulafill in dividend payout formulamake list of all complete sets2 . functions ordered by brokersprocess buy or sell orders ( run when an order comes in )( if for a bundle , treat each proxy asset in bundle as shown below ) receive transaction request and enter into databasedisplay order on screen with other unfilled ordersdisplay historical values of indicesdisplay cash account balancessearch for combinations of non - expired buy and sell orders of sameproxy asset identify matches in limit orders and numbers of sharesif found , execute orders through exchange of existing sharesif none found , combine order with other orders of same type ( e . g . buys forsame proxy asset ) if a bid for proxy assetsearch for complete set among bidsif total bid prices in set ≧ total cash account balancesthen : issue new shares create transaction records create complete set record fill in issuance records create investor records fill in historical cash balance changes record update number of shares and current cash balance in proxy asset recordif an offer to sell a proxy assetsearch for complete sets among offersif total offer prices in set ≦ total cash account balancesthen : redeem existing sharescreate transaction recordscreate complete set recordfill in redemption recordsupdate investor recordsfill historical cash balance changes recordupdate number of shares and current cash balance in proxy asset recordprovide information for electronic trading systemorder processing and confirmationprovide information for book window for trading screenprovide responses to requests for alerts - e . g ., alert traderswhen a specified price level has been reached either bya trade in subject proxy asset or by trades in otherproxy assets within the same complete set3 . functions ordered by investors ( informational web site ): view indicesview outstanding limit orders ( book window ) view composition of bundlesview proxy assetbase dateindices usedcash account balance per sharestarting cash account balance per sharecash account balance change historydividend payment historycash account formuladividend payout formula______________________________________ although the invention has been described in detail for the purpose of illustration , it is to be understood that such detail is solely for that purpose and that variations can be made therein by those skilled in the art without departing from the spirit and scope of the invention . indeed , some variations may need to be made to satisfy requirements of regulators , tax authorities , existing exchanges , brokers and underwriters , requirements that may vary through time and across countries .	6
a description will be given below of embodiments in accordance with the present invention with reference to the accompanying drawings . fig1 , 2 and 3 show one example of a welding method in accordance with the present invention , and show a case of applying a friction stir welding method to a lap joint . fig1 shows a material 1 and a material 2 corresponding to a weld material . a cavity portion 3 and a cavity portion 4 respectively having semicircular cross sectional shapes are formed in the material 1 and the material 2 . a cavity portion having a circular cross sectional shape is formed at a time of lapping the material 1 and the material 2 , thereby forming an embedded member 5 having an approximately equal cross sectional shape to the cavity portion . the material 1 and the material 2 corresponding to two weld materials having the cavity portions of the semicircular cross sectional shape are lapped via the embedded member 5 . both of the material 1 and the material 2 are made of an aluminum alloy . an applied material is essentially constituted by a material which can be friction stir welded . for example , metals such as a magnesium alloy , a copper alloy , a steel material and the like correspond thereto . both of thicknesses of the material 1 and the material 2 are 10 mm . a thickness of the applied material is determined on the basis of an applied material , a friction stir welding apparatus and a capacity of a rotating tool , however , in the case of the aluminum alloy , it is possible to apply to the thickness between about 0 . 5 mm and 100 mm . fig2 is a conceptual view of a state in which the material 1 , the material 2 and the embedded member 5 are set in such a manner as to be welded . the cavity portion 3 and the cavity portion 4 are lapped in such a manner that end portions thereof are aligned , and a cavity portion having a circular cross sectional shape is provided . the embedded member 5 is set to the cavity portion 7 . the cross sectional shape of the embedded member 5 is approximately equal to that of the cavity portion 7 . a radius of the cavity portion 7 formed by the cavity portion 3 and the cavity portion 4 having the semicircular cross sectional shape is about one half of the thickness of the material 1 . in other words , in order to form the weld portion having an excellent fatigue property , it is necessary to set a member having a larger radius of curvature than the unwelded portion formed near the weld portion . accordingly , the radius of the cavity portion 7 is larger than a gap of the lap surface formed by the material 1 and the material 2 , and is limited to one half of the thickness of the material 1 . the embedded member 5 is made of a steel material , and is harder than the material 1 and the material 2 . in order to form the weld portion which is excellent in the fatigue property , the cross sectional shape of the cavity portion 7 and the embedded member 5 is not limited to the circular shape , but may be changed as far as a cross sectional shape has a large radius of curvature . for example , an oval shape or the like corresponds thereto . further , fig2 shows a positional relation among the rotating tool 6 , a weld line and a weld surface . the rotating tool 6 is inserted from a direction which is in parallel to the weld surface 8 and is perpendicular to the weld surface 9 . an end surface 11 close to the embedded member 5 in a probe 10 existing in an end portion of the rotating tool 6 is inserted in such a manner as to be approximately in contact with the embedded member 5 , and a distance between the end surface 11 and the embedded member 5 at a time of inserting the rotating tool 6 is set to about 0 . 5 mm . fig3 shows a conceptual view of a state in which the rotating tool 6 is inserted to the weld surface 8 and the weld surface 9 , and the material 1 and the material 2 are welded along the weld line 12 . the rotating tool 6 is rotated in a clockwise direction as seen from the above of the rotating tool 6 . the weld makes progress toward a far side from a near side of the material . as shown in fig3 , a stir zone 13 stirred by the rotating tool 6 is formed in the weld portion in such a manner as to be in contact with the embedded member 5 . in accordance with the structure mentioned above , the unwelded portion is not formed between the stir zone 13 and the embedded member 5 . fig4 shows a cross section to which the friction stir welding is applied by forming only the cavity portion without using the embedded member 5 . a positional relation between a material 14 and a material 15 is shown by a dotted line 16 . a cavity portion obtained by lapping the semicircular cross sectional shape is provided on a surface in which the material 14 and the material 15 are brought into contact with each other . a shape of the cavity portion before the friction stir welding is applied thereto has a circular cross sectional shape as described by a dotted line 17 . a shape of the rotating tool 18 is structured such that a diameter of a shoulder portion is 10 mm , a diameter of a probe 20 is 4 mm , and a length of the probe 20 is 10 mm . a description will be given of a positional relation between the rotating tool 18 and the cavity portion 17 by using fig4 . when the rotating tool 18 is inserted to the material 14 and the material 15 , a distance between an end surface 21 of the probe 20 close to the cavity portion and the cavity portion 17 is 0 . 2 mm . a rotating speed of the rotating tool 18 is set to 1000 rotation / min , and a welding speed is set to 100 mm / min . as is understood from fig4 , a shape of the cavity portion 17 after the friction stir welding is applied thereto is largely deformed , and loses the circular shape . this is because about some hundreds kg to about one ton load is applied to the weld portion by inserting and traveling the rotating tool 18 at a time of the friction stir welding , whereby the material exposed to the load of the material 14 and the material 15 flows into the cavity portion in case that a backing metal supporting the load does not exist . as mentioned above , the shape of the cavity portion provided for improving the fatigue property of the weld portion collapses . in other words , since the surface having the large radius of curvature does not exist near the weld portion , and the unwelded portion is formed in the weld surface 23 , the stress concentration to the weld portion becomes higher and the fatigue property is deteriorated , in the case that the stress is applied in the perpendicular direction to the weld surface 23 . on the contrary , fig5 shows a cross section photograph in the case that the friction stir welding is applied by using the embedded member . the positional relation between the rotating tool 18 and an embedded member 24 after the end of the welding is shown in fig5 . a welding condition is approximately equal to that shown in fig4 . there can be observed that the unwelded defect does not appear between the rotating tool 18 and the embedded member 24 , and a complete weld is achieved . even in the case that the stress is applied to the weld portion , the unwelded portion is not formed , and the surface to which the stress is applied exhibits the large curvature , so that it is possible to avoid the stress concentration . as mentioned above , it is possible to improve the fatigue property of the weld portion by setting the embedded member in the cavity portion having the circular cross section so as to weld . fig6 shows a conceptual view of a case that the welding method is applied to the weld structure . the weld structure is constituted by a pressure container , and is structured such that a material 25 corresponding to a container and a material 26 corresponding to a lid are lapped over such that end portions are aligned with each other . a circular cavity portion 28 is provided in a surface 27 in which the material 25 and the material 26 are in contact with each other . a member 29 having an approximately equal cross sectional shape is embedded in the cavity portion 28 . the material 25 and the material 26 are welded in accordance with a friction stir welding method by using a rotating tool 30 . a positional relation between the rotating tool 30 and the weld surface and a positional relation between the rotating tool 30 and the embedded member 29 is the same as those of fig1 , 2 and 3 . the unwelded portion is not formed between a stir zone 31 formed thereby and the embedded member 29 even by applying the friction stir welding , and a surface having a large curvature is obtained . a space 32 is formed in an inner side thereof by welding the material 25 and the material 26 . in the case that a repeated stress is applied to a direction perpendicular to the surface 27 by the space 32 , the unwelded portion is not formed , so that it is possible to form a weld portion which is excellent in a fatigue strength . the weld mentioned above can be applied to a weld structure to which the repeated stress is applied , for example , a cooling apparatus having a water channel , a pressure container or the like . fig7 , 8 and 9 show a welding method in accordance with the other embodiment of the present invention . the present embodiment corresponds to a case that the present invention is applied to a lap joint , however , shapes of a material 33 and a material 34 are different from the material 1 and the material 2 of the embodiment 1 . fig7 shows a positional relation among the material 33 and the material 34 , a cavity portion 38 having a semicircular cross sectional shape and a cavity portion 39 having a semicircular cross sectional shape , and an embedded member 40 having a circular cross sectional shape . the cavity portion 38 and the cavity portion 39 are provided on a surface in which the material 33 and the material 34 are brought into contact with each other , that is , a butt weld surface 35 and a butt weld surface 36 . both of the material 33 and the material 34 are made of an aluminum alloy . the embedded member 40 is made of a harder material than the material 33 and the material 34 , and is made of a steel material . thicknesses of the material 33 and the material 34 are the same as those shown in the embodiment 1 . fig8 is a conceptual view showing a state in which the material 33 , the material 34 , the cavity portion 38 , the cavity portion 39 and the embedded member 40 are set in such a manner as to be welded . fig8 shows a positional relation among the butt weld surface 35 , the butt weld surface 36 and a rotating tool 37 . the rotating tool 37 is inserted from a direction perpendicular to the butt weld surface 35 and the butt weld surface 36 . a cavity portion 41 having a circular cross sectional shape is provided by lapping the cavity portion 38 and the cavity portion 39 in such a manner that end portions thereof are aligned with each other . the embedded member 40 is set to the cavity portion 41 . a cross sectional shape of the embedded member 40 is approximately equal to the cavity portion 41 . a radius of the cavity portion 41 formed by the cavity portion 38 having the semicircular cross sectional shape and the cavity portion 39 having the semicircular cross sectional shape is approximately one half of a thickness of the material 33 , and is set to the same as described in the embodiment 1 . a positional relation between an end surface 43 of the embedded member 40 side in the probe 42 at a time of inserting the rotating tool 37 and the embedded member 40 is the same as described in the embodiment 1 . fig9 shows a conceptual view of a state in which the material 33 and the material 34 are welded by inserting the rotating tool 37 to the butt weld surface 35 and the butt weld surface 36 from a direction of the material 33 while keeping the positional relation between the end surface 43 and the embedded member 40 . the rotating tool 37 is rotated in a clockwise direction as seen from the above of the rotating tool 37 . a frictional stir welding makes progress toward a far side from a near side of the drawing . as shown in fig9 , a stir zone 44 stirred by the rotating tool 37 is formed in the weld portion in such a manner as to be in contact with the embedded member 40 , and an unwelded portion is not formed between the stir zone and the embedded member 40 . as a result , it is possible to improve a fatigue characteristic of the weld portion . fig1 , 11 and 12 show the other embodiment in accordance with the present invention . the embodiment corresponds to a case that the frictional stir welding is applied to a butt joint . fig1 shows a positional relation among a material 45 and a material 46 , a cavity portion 47 having a semicircular cross sectional shape and a cavity portion 48 having a semicircular cross sectional shape , and an embedded member 49 having a circular cross sectional shape . the cavity portion 47 and the cavity portion 48 are provided on a surface in which the material 45 and the material 46 are brought into contact with each other . both of the material 45 and the material 46 are made of an aluminum alloy . an applied material is the same as described in the embodiment 1 . thicknesses of the material 45 and the material 46 are both set to 10 mm . fig1 is a conceptual view showing a state in which the material 45 , the material 46 , the cavity portion 47 , the cavity portion 48 and the embedded member 49 are set in such a manner as to be welded . a cavity portion 50 having a circular cross sectional shape is provided by lapping the cavity portion 47 and the cavity portion 48 in such a manner that end portions thereof are aligned with each other . a cross sectional shape of the embedded member 49 is approximately equal to the cavity portion 50 . a radius of the cavity portion 50 formed by the cavity portion 47 and the cavity portion 48 is approximately one half of a thickness of the material 45 and the material 46 . fig1 shows a positional relation between a rotating tool 51 and a weld line . the rotating tool 51 is inserted from a direction perpendicular to a butt weld line 53 . a lower end surface 55 in a probe 54 existing in an end portion of the rotating tool 51 is inserted to a position which is approximately in contact with the embedded member 49 , and a distance between the end surface 55 and the embedded member 49 at a time of inserting the rotating tool 51 is set to about 0 . 1 mm . fig1 shows a conceptual view of a state in which the material 45 and the material 46 are welded by inserting the rotating tool 51 along the weld line 53 . the rotating tool 51 is rotated in a clockwise direction as seen from the above of the rotating tool 51 . a welding makes progress toward a far side from a near side of the drawing . as shown in fig1 , a stir zone 56 stirred by the rotating tool 51 is formed in the weld portion in such a manner as to be in contact with the embedded member 49 . in accordance with the structure mentioned above , an unwelded portion is not formed between the stir zone 56 and the embedded member 49 . a load from about some hundreds of kg to about one ton is applied to the weld portion by inserting and traveling the rotating tool 51 at a time of the friction stir welding , however , since the embedded member 49 supporting the load is provided , the curvature is not changed , and the unwelded portion is not formed , so that it is possible to support the load . in the case that a repeated stress is applied in a perpendicular direction to the weld surface , the unwelded portion is not formed . accordingly , it is possible to form the weld portion which is excellent in a fatigue strength . in accordance with these embodiments , since the unwelded portion is not formed near the cavity portion , the notch effect is reduced , and it is possible to form the weld member which is excellent in the fatigue property . the present invention relates to the friction stir welding method of welding in a state in which the cavity portion is provided in the weld surface , and the embedded member is formed in the cavity portion , in the case of applying the friction stir welding . it should be further understood by those skilled in the art that although the foregoing description has been made on embodiments of the invention , the invention is not limited thereto and various changes and modifications may be made without departing from the spirit of the invention and the scope of the appended claims .	1
the following definitions are used , unless otherwise described : halo is fluoro , chloro , bromo , or iodo . alkyl , alkoxy , alkenyl , alkynyl , etc . denote both straight and branched groups ; but reference to an individual group such as “ propyl ” embraces only the straight chain variant , a branched chain isomer such as “ isopropyl ” being specifically referred to . bicyclic aryl denotes an ortho - fused bicyclic carbocyclic substituent having about nine to ten ring atoms in which at least one ring is aromatic . monocyclic heteroaryl encompasses a substituent attached via a ring carbon of a monocyclic aromatic ring containing five or six ring atoms consisting of carbon and one to four heteroatoms each selected from the group consisting of non - peroxide oxygen , sulfur , and n ( x ) wherein x is absent or is h , o , ( c 1 – c 4 ) alkyl , phenyl or benzyl . bicyclic heteroaryl encompasses a substituent of an ortho - fused bicyclic heterocycle of about eight to ten ring atoms derived therefrom , particularly a benzyl - derivative or one derived by fusing a propylene , trimethylene , or tetramethylene divalent substituent thereto . bicyclic alkyl encompasses a substituent of an ortho - fused bicyclic alkyl of about eight to ten ring atoms containing five or six ring atoms consisting of carbon and one to four ring atoms consisting of heteroatoms selected from the group consisting of non - peroxide oxygen , sulfur , and n ( x ) wherein x is absent or is h , o , ( c 1 – c 4 ) alkyl , phenyl or benzyl . it will be appreciated by those skilled in the art that compounds of the invention having a chiral center may exist in and be isolated in optically active and racemic forms . some compounds may exhibit polymorphism . it is to be understood that the present invention encompasses any racemic , optically - active , polymorphic , or stereoisomeric form , or mixtures thereof , of a compound of the invention , which possess the useful properties described herein , it being well known in the art how to prepare optically active forms ( for example , by resolution of the racemic form by recrystallization techniques , by synthesis from optically - active starting materials , by chiral synthesis , or by chromatographic separation using a chiral stationary phase ) and how to determine mmp inhibition activity using the standard tests described hereinbelow , or using other similar tests which are well known in the art . as used herein , “ ovulation ” is the release of an ovum from the ovarian follicle . stedman &# 39 ; s medical dictionary , 25th ed ., illustrated , williams & amp ; wilkins , baltimore , 1990 , p . 1116 . as used herein , “ ovum ” is the female sex ( reproductive ) cell . when fertilized by a spermatozoon , an ovum is capable of developing into a new individual of the same species . stedman &# 39 ; s medical dictionary , 25th ed ., illustrated , williams & amp ; wilkins , baltimore , 1990 , p . 1116 . as used herein , “ fertilization ” is the process beginning with penetration of the secondary oocyte by the spermatozoon and completed by infusion of the male and female pronuclei . stedman &# 39 ; s medical dictionary , 25th ed ., illustrated , williams & amp ; wilkins , baltimore , 1990 , p . 573 . as used herein , a “ uterus ” is the womb , metra , or the hollow muscular organ in which the impregnated ovum is developed into the child . stedman &# 39 ; s medical dictionary , 25th ed ., illustrated , williams & amp ; wilkins , baltimore , 1990 , pp . 1677 – 1678 . specific and preferred values listed below for substituents ( i . e ., groups ) and ranges are for illustration only ; they do not exclude other defined values or other values within defined ranges for the substituents specifically , ( c 1 – c 6 ) alkyl can be methyl , ethyl , propyl , isopropyl , butyl , iso - butyl , sec - butyl , pentyl , 3 - pentyl , or hexyl ; ( c 1 – c 6 ) alkoxy can be methoxy , ethoxy , propoxy , isopropoxy , butoxy , iso - butoxy , sec - butoxy , pentoxy , 3 - pentoxy , or hexyloxy ; ( c 2 – c 6 ) alkenyl can be vinyl , allyl , 1 - propenyl , 2 - propenyl , 1 - butenyl , 2 - butenyl , 3 - butenyl , 1 - pentenyl , 2 - pentenyl , 3 - pentenyl , 4 - pentenyl , 1 - hexenyl , 2 - hexenyl , 3 - hexenyl , 4 - hexenyl , or 5 - hexenyl ; ( c 2 – c 6 ) alkynyl can be ethynyl , 1 - propynyl , 2 - propynyl , 1 - butynyl , 2 - butynyl , 3 - butynyl , 1 - pentynyl , 2 - pentynyl , 3 - pentynyl , 4 - pentynyl , 1 - hexynyl , 2 - hexynyl , 3 - hexynyl , 4 - hexynyl , or 5 - hexynyl ; ( c 1 – c 6 ) alkanoyl can be acetyl , propanoyl or butanoyl ; ( c 2 – c 6 ) alkanoyloxy can be acetoxy , propanoyloxy , butanoyloxy , isobutanoyloxy , pentanoyloxy , or hexanoyloxy ; ( c 3 – c 8 ) cycloalkyl can be cyclopropyl , cyclobutyl , cyclopentyl , cyclohexyl , cycloheptyl , or cyclooctyl ; aryl can be phenyl , indenyl , 5 , 6 , 7 , 8 - tetrahydronaphthyl , or naphthyl and heteroaryl can be furyl , imidazolyl , tetrazolyl , pyridyl , ( or its n - oxide ), thienyl , pyrimidinyl ( or its n - oxide ), indolyl , or quinolyl ( or its n - oxide ); bicyclic aryl can be indenyl or naphthyl ; monocyclic heteroaryl can be furyl , imidazolyl , triazolyl , triazinyl , oxazoyl , isoxazoyl , thiazolyl , isothiazoyl , pyrazolyl , pyrrolyl , pyrazinyl , tetrazolyl , pyridyl ( or its n - oxide ), thienyl , or pyrimidinyl ( or its n - oxide ), bicyclic heteroaryl can be quinolyl ( or its n - oxide ); and bicyclic alkyl can be decahydroquinoline or decahydronaphthalene ( cis and trans ). as used herein , an “ amino acid ” is a natural amino acid residue ( e . g . ala , arg , asn , asp , cys , glu , gln , gly , his , hyl , hyp , ile , leu , lys , met , phe , pro , ser , thr , trp , tyr , and val ) in d or l form , as well as unnatural amino acid ( e . g . phosphoserine ; phosphothreonine ; phosphotyrosine ; hydroxyproline ; gamma - carboxyglutamate ; hippuric acid ; octahydroindole - 2 - carboxylic acid ; statine ; 1 , 2 , 3 , 4 ,- tetrahydroisoquinoline - 3 - carboxylic acid ; penicillamine ; ornithine ; citruline ; a - methyl - alanine ; para - benzoylphenylalanine ; phenylglycine ; propargylglycine ; sarcosine ; and tert - butylglycine ) residue having one or more open valences . the term also comprises natural and unnatural amino acids bearing amino protecting groups ( e . g . acetyl , acyl , trifluoroacetyl , or benzyloxycarbonyl ), as well as natural and unnatural amino acids protected at carboxy with protecting groups ( e . g . as a ( c 1 – c 6 ) alkyl , phenyl or benzyl ester or amide ). other suitable amino and carboxy protecting groups are known to those skilled in the art ( see for example , t . w . greene , protecting groups in organic synthesis ; wiley : new york , 1981 ; d . voet , biochemistry , wiley : new york , 1990 ; l . stryer , biochemistry , ( 3rd ed . ), w . h . freeman and co . : new york , 1975 ; j . march , advanced organic chemistry , reactions , mechanisms and structure , ( 2nd ed . ), mcgraw hill : new york , 1977 ; f . carey and r . sundberg , advanced organic chemistry , part b : reactions and synthesis , ( 2nd ed . ), plenum : new york , 1977 ; and references cited therein ). according to the invention , the amino or carboxy protecting group can also comprise a radionuclide ( e . g ., fluorine - 18 , iodine - 123 , or iodine - 124 ). as used herein , an “ electrophile ” refers to a chemical species , ion , or a portion of a compound which , in the course of a chemical reaction , will acquire electrons , or share electrons , to form other molecules or ions . electrophiles are ordinarily thought of as cationic species ( positively charged ). mcgraw - hill concise encyclopedia of science & amp ; technology , mcgraw - hill , p . 715 , 4 th edition , new york , n . y . ( 1998 ). as used herein , a “ nucleophile ” refers to a chemical species , ion , or a portion of a compound which , in the course of a chemical reaction , will lose electrons , or share electrons , to form other molecules or ions . nucleophiles are ordinarily thought of as anionic species ( negatively charged ). typical nucleoplic species include , e . g ., hydroxyl ( oh ), halo ( f , cl , br , or i ), cyano ( cn ), alkoxy ( ch 3 ch 2 o ), carboxyl ( coo ), and thio ( s ). mcgraw - hill concise encyclopedia of science & amp ; technology , mcgraw - hill , p . 715 , 4 th edition , new york , n . y . ( 1998 ). as used herein , a “ peptide ” is a sequence of 2 to 25 amino acids ( e . g . as defined hereinabove ) or peptidic residues having one or more open valences . the sequence may be linear or cyclic . for example , a cyclic peptide can be prepared or may result from the formation of disulfide bridges between two cysteine residues in a sequence . a peptide can be linked through the carboxy terminus , the amino terminus , or through any other convenient point of attachment , such as , for example , through the sulfur of a cysteine . peptide derivatives can be prepared as disclosed in u . s . pat . nos . 4 , 612 , 302 ; 4 , 853 , 371 ; and 4 , 684 , 620 . peptide sequences specifically recited herein are written with the amino terminus on the left and the carboxy terminus on the right . as used herein , a “ hydrophobic group ” or “ hydrophobic moiety ” refers to a group that is relatively non - polar and will have a relatively minimal affinity for water . the nature of the hydrophobic group ( i . e ., a — x — m ) is not important , provided the hydrophobic group fits into the pocket and has a favorable interaction ( e . g ., binding ) with the enzyme . the hydrophobic group , while being relatively hydrophobic , can include one or more heteroatoms ( e . g ., s , o , or n ) that can have an electrostatic charge or can include one or more groups ( e . g ., esters or amides ) that can have an electrostatic charge , provided the hydrophobic group fits into the pocket and has a favorable interaction with the enzyme . any suitable hydrophobic group can be employed as a — x — m , provided the hydrophobic group fits into the pocket and has a favorable interaction ( e . g ., binding ) with the enzyme . for example , the hydrophobic group can include a straight - chained or branched hydrocarbon chain ( e . g ., alkyl , alkenyl , or alkynyl ), an aryl group ( e . g ., monocyclic or bicylic ), a heteroaryl group ( e . g ., monocyclic or bicylic ), a cycloalkyl group , an amino acid , a peptide , or a combination thereof . in one embodiment , a — x — m can be a saturated or partially unsaturated hydrocarbon chain comprising one or more carbon atoms and optionally comprising one or more oxy (— o —), thio (— s —), sulfinyl (— so —), sulfonyl ( s ( o ) 2 —), or nr f in the chain , wherein each r f is independently hydrogen or ( c 1 – c 6 ) alkyl . the saturated or partially unsaturated hydrocarbon chain can optionally be substituted with one or more oxo (═ o ), hydroxy , cyano , halo , nitro , trifluoromethyl , trifluoromethoxy , ( c 1 – c 6 ) alkyl , ( c 1 – c 6 ) alkoxy , ( c 1 – c 6 ) alkoxy ( c 1 – c 6 ) alkyl , ( c 3 – c 6 ) alkyl , c 3 – c 8 ) cycloalkyl , aryl , heteroaryl , ( c 3 – c 8 ) cycloalkyl ( c 1 – c 6 ) alkyl , ( aryl )( c 1 – c 8 ) alkyl , ( heteroaryl )( c 1 – c 6 ) alkyl , ( c 3 – c 8 ) cycloalkyl oxy , ( aryl ) oxy , ( heteroaryl ) oxy , ( c 3 – c 8 ) cycloalkyl , ( aryl ) oxy ( aryl ), ( heteroaryl ) oxy ( heteroaryl ), ( c 3 – c 8 ) cycloalkyl oxy ( c 1 – c 6 ) alkyl , ( aryl ) oxy ( c 1 – c 6 ) alkyl , or ( heteroaryl ) oxy ( c 1 – c 6 ) alkyl . in addition , any aryl , ( c 3 – c 8 ) cycloalkyl , or heteroaryl can optionally be substituted with one or more oxo (═ o ), hydroxy , cyano , halo , nitro , trifluoromethyl , trifluoromethoxy , ( c 1 – c 6 ) alkyl , ( c 1 – c 6 ) alkoxy , ( c 1 – c 6 ) alkoxy ( c 1 – c 6 ) alkyl , ( c 3 – c 8 ) cycloalkyl , aryl , heteroaryl , ( c 3 – c 8 ) cycloalkyl ( c 1 – c 6 ) alkyl , ( aryl )( c 1 – c 8 ) alkyl , ( heteroaryl )( c 1 – c 6 ) alkyl , ( c 3 – c 8 ) cycloalkyl oxy , ( aryl ) oxy , ( heteroaryl ) oxy , ( c 3 – c 8 ) cycloalkyl , ( aryl ) oxy ( aryl ), ( heteroaryl ) oxy ( heteroaryl ), ( c 3 – c 8 ) cycloalkyl oxy ( c 1 – c 6 ) alkyl , ( aryl ) oxy ( c 1 – c 6 ) alkyl , or ( heteroaryl ) oxy ( c 1 – c 6 ) alkyl . when a — x — m is a “ partially unsaturated ” group , such group may comprise one or more ( e . g . 1 or 2 ) carbon - carbon double or triple bonds . for example , when a — x — m is a partially unsaturated ( c 1 – c 6 ) alkyl , it can be vinyl , allyl , 1 - propenyl , 2 - propenyl , 1 - butenyl , 2 - butenyl , 3 - butenyl , 1 , 3 - butadienyl , 1 - pentenyl , 2 - pentenyl , 3 - pentenyl , 4 - pentenyl , 1 - hexenyl , 2 - hexenyl , 3 - hexenyl , 4 - hexenyl , 2 , 4 - hexadienyl , 5 - hexenyl , ethynyl , 1 - propynyl , 2 - propynyl , 1 - butynyl , 2 - butynyl , 3 - butynyl , 1 - pentynyl , 2 - pentynyl , 3 - pentynyl , 4 - pentynyl , 5 - hexene - 1 - ynyl , 2 - hexynyl , 3 - hexynyl , 3 - hexen - 5 - ynyl , 4 - hexynyl , or 5 - hexynyl . a specific value for a — x — m is a and m are each independently phenyl or monocyclic heteroaryl , wherein any phenyl or heteroaryl is optionally substituted with one or more ( e . g ., 1 , 2 , 3 , or 4 ) hydroxy , ( c 1 – 6 ) alkyl , ( c 1 – c 6 ) alkanoyl , ( c 1 – c 6 ) alkanoyloxy , ( c 1 – c 6 ) alkoxy , cyano , nitro , halo , trifluoromethyl , trifluoromethoxy , sr , nrr , or coor ; and x is o , s , so , so 2 , c (═ o ) nr , c (═ o ) o , nrc (═ o ), oc (═ o ), nr , a direct bond , or ( c 1 – c 6 ) alkyl optionally substituted with one or more hydroxy , ( c 1 – c 6 ) alkoxy , cyano , nitro , halo , sr , nrr , or coor . another specific value for a — x — m is bicyclic aryl ( e . g ., naphthyl ), bicyclic heteroaryl , or bicyclic alkyl ; wherein any aryl , heteroaryl or alkyl is optionally substituted with one or more ( e . g ., 1 , 2 , 3 , or 4 ) hydroxy , ( c 1 – c 6 ) alkyl , ( c 1 – c 6 ) alkanoyl , ( c 1 – c 6 ) alkanoyloxy , ( c 1 – c 6 ) alkoxy , cyano , nitro , halo , trifluoromethyl , trifluoromethoxy , sr , nrr , or coor ; wherein each r is independently h , ( c 1 – c 6 ) alkyl , phenyl , benzyl , or phenethyl . a specific value for a is phenyl or monocyclic heteroaryl . another specific value for a is phenyl . a specific value for m is phenyl or monocyclic heteroaryl . another specific value for m is phenyl . a specific value for x is o , s , so , so 2 , c (═ o ) nr , c (═ o ) o , nrc (═ o ), oc (═ o ), nr , a direct bond , or ( c 1 – c 6 ) alkyl . another specific value for x is o . x ′ is o , ( c 1 – c 6 ) alkyl ( e . g ., ch 2 ), or a direct bond ; y ′ is n or ( c 1 – c 6 ) alkyl ( e . g ., ch 2 ); and z ′ is halo , ( c 1 – c 6 ) alkoxy ( e . g ., och 3 ), or hydroxy . z ′ is halo , ( c 1 – c 6 ) alkoxy ( e . g ., och 3 ), or hydroxy . z ′ is halo , ( c 1 – c 6 ) alkoxy ( e . g ., och 3 ), or hydroxy . r ′ is o , ( c 1 – c 6 ) alkyl ( e . g ., ch 2 ), or s ; and a specific value for e is ( c 1 – c 6 ) alkyl . another specific value for e is methyl . a specific value for ( c 1 – c 6 ) alkyl is methyl . a specific compound of the present invention is a compound of formula ( i ) wherein a is phenyl , m is phenyl , x is o , d is so 2 , e is methyl , j is s , g is hydrogen , t is hydrogen , and q is hydrogen . fig2 illustrates a synthesis for compounds 1 - 4 . 4 - phenoxythiophenol 10 was prepared from the commercially available 4 - phenoxyphenol 7 via the 3 step procedure illustrated by newman and karnes . newman m . s . ; karnes h . a . j . org . chem ., 1996 , 31 , 3980 – 3984 . subsequent alkylation of 10 with allyl bromide , 4 - bromo - 1 - butene and 5 - bromo - 1 - pentene respectively , led to the sulfanyl compounds 11 – 13 in good yield . although the epoxidation of 12 and 13 with mcpba was relatively quick , taking only 2 – 3 days , the formation of 11 took 7 days and required a large excess of mcpba . finally , the conversion of the epoxides 4 – 6 to their corresponding thiirane derivatives 1 – 3 , was accomplished via the treatment of each epoxide with ammoniumthiocyanate in thf / water . although the thiiranes 2 and 3 were isolated in high yield , 93 % and 85 % respectively , thiirane 1 could only be recovered in a very poor ( i . e ., 14 %) yield . processes for preparing compounds of formula ( i ) or for preparing intermediates useful for preparing compounds of formula ( i ) are provided as further embodiments of the invention . intermediates useful for preparing compounds of formula ( i ) are also provided as further embodiments of the invention . a compound of formula ( i ) wherein j is s can be prepared by treating a corresponding compound of formula ( i ) wherein j is o with a suitable sulfonating reagent . see , e . g ., march , advanced organic chemistry reactions , mechanisms and structure , 2 nd ed ., 1977 and carey & amp ; sundberg , advanced organic chemistry , part b : reactions , 2 nd ed ., 1983 . a compound of formula ( i ) wherein j is o can be prepared by epoxidizing a corresponding compound of formula ( i ) wherein the ring that includes j is an alkene . see , e . g ., march , advanced organic chemistry , reactions , mechanisms and structure , 2 nd ed ., 1977 and carey & amp ; sundberg , advanced organic chemistry , part b : reactions , 2 nd ed ., 1983 . a compound of formula ( i ) wherein d is so 2 and j is o can be prepared by oxidizing a corresponding compound of formula ( i ) wherein d is s . see , e . g ., march , advanced organic chemistry , reactions , mechanisms and structure , 2 nd ed ., 1977 and carey & amp ; sundberg , advanced organic chemistry , part b : reactions , 2 nd ed ., 1983 . a specific group of the compounds of the present invention , that can be activated by zinc for nucleophilic substitution and that can form a covalent bond with a nucleophile of the matrix metalloproteinase , includes a thiirane ring . another specific group of the compounds of the present invention , that can be activated by zinc for nucleophilic substitution and that can form a covalent bond with a nucleophile of the matrix metalloproteinase , includes an oxirane ring . in addition , a specific nucleophile of the matrix metalloproteinase which can form a covalent bond with the group of the compounds of the present invention ( e . g ., thiirane or oxirane ) is located at the amino acid residue corresponding to residue 404 of the matrix metalloproteinase , wherein the numbering is based on the active site general base for gelatinase a , which is observed in other mmps . more specifically , the nucleophile is a carboxy ( i . e ., coo − ) oxygen atom located at amino acid residue corresponding to residue 404 of the matrix metalloproteinase , wherein the numbering is based on the active site general base for gelatinase a , which is observed in other mmps . see , fig1 . the matrix metalloproteinase can be a human matrix metalloproteinase . in addition , the matrix metalloproteinase can be a gelatinase , collagenase , stromelysin , membrane - type mmp , or matrilysin . specifically , the gelatinase can be mmp - 2 or mmp - 9 . according to the method of the invention , the matrix metalloproteinase can be contacted with the compound , e . g ., a compound of formula ( i ), in vitro . alternatively , the matrix metalloproteinase can be contacted with the compound , e . g ., a compound of formula ( i ), in vivo . without being bound by any particular theory , coordination of a thiirane in a compound of formula ( i ) with the enzyme active - site zinc ion is believed to activate the thiirane for modification by a nucleophile of the enzyme . see , fig1 . a computational model based on three - dimensional homology modeling for this enzyme with compound 1 indicates that the biphenyl group would fit in the active site analogously to the same group in certain known reversible inhibitors of mmp - 2 and mmp - 9 , as analyzed by x - ray structure determination . freskos , j . n . ; mischke b . v . ; decrescenzo , g . a . ; heintz , r . ; getman , d . p . ; howard , s . c . ; kishore , n . n . ; mcdonald , j . j . ; munie , g . e . ; rangwala , s . ; swearingen , c . a . ; voliva , c . ; welsch , d . j . bioorg . & amp ; med . chem . letters , 1999 , 9 , 943 – 948 . tamura , y . ; watanabe , f . ; nakatani , t . ; yasui , k . ; fuji , m . ; komurasaki , t . ; tsuzuki , h . ; maekawa , r . ; yoshioka , t . ; kawada , k . ; sugita , k . ; ohtani , m . j . med . chem . 1998 , 41 , 640 – 649 . as such , the biphenyl ether moiety in compounds 1 – 4 is believed to fit in the p1 ′ subsite of gelatinases , which is a deep hydrophobic pocket . ( a ) morgunova , e . ; tuuttila , a . ; bergmann , u . ; isupov , m . ; lindqvist , y . ; schneider , g . ; tryggvason , k . science 1999 , 284 , 1667 – 1670 . ( b ) massova , i . ; fridman , r . ; mobashery , s . j . mol . mod . 1997 , 3 , 17 – 34 ; olson , m . w . ; bernardo , m . m . ; pietila , m . ; gervasi , d . c . ; toth , m . ; kotra , l . p . ; massova , i . ; mobashery , s . ; fridman , r . j . biol . chem ., 2000 , 275 , 2661 – 2668 . this binding mode brings the sulfur of the thiirane in i into the coordination sphere of the zinc ion . see , fig1 . the models also indicated that the thiirane moiety in compounds 2 and 3 , with longer carbon backbones , would not be able to coordinate with the zinc ion as well as compound 1 , but would fit in an extended configuration in the active site . it is believed that the high specificity of certain compounds of the invention for a targeted enzyme arises predominantly from three factors . ( i ) the compounds satisfy the binding specificity requirements at the active site . in this respect these compounds are not any different from conventional reversible or affinity inhibitors . ( ii ) furthermore , the structural features of the inhibition should allow it to undergo chemical activation by the zinc atom of the enzyme to generate an electrophilic species within the active site . ( iii ) finally , there should be a nucleophilic amino - acid residue in the active site , in the proper orientation , to react with the electrophilic species ( e . g ., thiirane ring ), resulting in irreversible enzyme inactivation . by selecting a hydrophobic group ( e . g ., a — x — m ) located a specific distance from a group ( e . g ., d ) that can bind ( e . g ., hydrogen bond ) with one or more sites in the enzyme ( e . g ., amino acid residue 191 and / or amino acid residue 192 , in gelatinase a ), which is in turn located a specific distance from a thiirane ring that can coordinate with the enzyme active - site zinc atom , one can prepare selective mechanism - based inhibitors for a given mmp . see , fig1 . accordingly , preferred mmp inhibitors have a hydrophobic aryl moiety ( e . g ., a — x — m ) that can fit in the deep hydrophobic pocket ( i . e ., p 1 ′ subsite ) of an mmp . in addition , preferred mechanism - based mmp inhibitors also have a thiirane ring that can coordinate with the enzyme active - site zinc ion , and be modified by a nucleophile ( e . g ., carboxylate group of amino acid residue 404 of mmp - 2 ) in the enzyme active site . see , fig1 . the preferred mmp inhibitors can optionally include a second group ( e . g ., d ) that can coordinate with one or more sites in the enzyme . specifically , the second group can optionally hydrogen bond to the one or two proton donors ( e . g ., amino acid residue corresponding to residue 191 and / or amino acid residue corresponding to residue 192 of mmp - 2 ) in the enzyme active site . see , fig1 . the present invention provides a method for identifying a mechanistic based mmp inhibitor . the method includes providing a compound wherein ( 1 ) a hydrophobic moiety of the compound fits into a hydrophobic pocket of the mmp ; ( 2 ) the compound has one or two groups that can hydrogen bond with one or two hydrogen donors of the mmp , wherein the hydrogen donors of the mmp are located at amino acid residue corresponding to residue 191 and amino acid residue corresponding to residue 192 of mmp - 2 ; ( 3 ) the compound has an electrophilic group that can covalently bond with a nucleophile of the mmp , wherein the nucleophile of the mmp is located at amino acid residue corresponding to residue 404 of mmp - 2 ; and / or ( 4 ) the compound includes a group that can coordinate with the zinc ion of the mmp . preferred mmp inhibitors have a thiirane or oxirane such that the sulfur or oxygen atom of the thiirane or oxirane is located about 3 angstroms to about 4 angstroms from the zinc ion . the suitable mmp inhibitors can also include a thiirane or oxirane ring located about 3 angstroms to about 5 angstroms from the active site nucleophile . see , fig1 and 3 . radiolabeled compounds of formula ( i ) are also useful as imaging agents for imaging cells comprising mmp &# 39 ; s . accordingly , the invention also provides compounds of formula ( i ) that include one or more detectable radionuclides ( e . g ., one or more metallic radionuclide and / or one or more non - metallic radionuclides ). for example , a detectable radionuclide can be incorporated into a compound by replacing an atom of the compound of formula ( i ) with a radionuclide ( e . g ., non - metallic radionuclide ). alternatively , a radiolabeled compound of the invention can be prepared by linking a compound of formula ( i ) to a chelating group that includes a detectable radionuclide ( e . g ., metallic radionuclide ). such compounds can be useful to image tissues with mmp activity or tumors , in vivo or in vitro . as used herein , a “ chelating group ” is a group that can include a detectable radionuclide ( e . g ., a metallic radioisotope ). any suitable chelating group can be employed . suitable chelating groups are disclosed , e . g ., in poster sessions , proceedings of the 46th annual meeting , j . nuc . med ., p . 316 , no . 1386 ; scientific papers , proceedings of the 46th annual meeting , j . nuc . med ., p . 123 , no . 499 ; scientific papers , proceedings of the 46th annual meeting , j . nuc . med ., p . 102 , no . 413 ; scientific papers , proceedings of the 46th annual meeting , j . nuc . med ., p . 102 , no . 414 ; scientific papers , proceedings of the 46th annual meeting , j . nuc . med ., p . 103 , no . 415 ; poster sessions , proceedings of the 46th annual meeting , j . nuc . med ., p . 318 , no . 1396 ; poster sessions , proceedings of the 46th annual meeting , j . nuc . med ., p . 319 , no . 1398 ; m . moi et al ., j . amer . chem ., soc ., 49 , 2639 ( 1989 ); s . v . deshpande et al ., j . nucl . med ., 31 , 473 ( 1990 ); g . kuser et al ., bioconj . chem ., 1 , 345 ( 1990 ); c . j . broan et al ., j . c . s . chem . comm ., 23 , 1739 ( 1990 ); c . j . anderson et al ., j . nucl . med . 36 , 850 ( 1995 ); u . s . pat . nos . 5 , 739 , 313 ; and u . s . pat . no . 6 , 004 , 533 . specifically , the chelating group can be . as used herein , a “ detectable radionuclide ” is any suitable radionuclide ( i . e ., radioisotope ) useful in a diagnostic procedure in vivo or in vitro . suitable detectable radionuclides include metallic radionuclides ( i . e ., metallic radioisotopes ) and non - metallic radionuclides ( i . e ., non - metallic radioisotopes ). suitable metallic radionuclides ( i . e ., metallic radioisotopes or metallic paramagnetic ions ) include antimony - 124 , antimony - 125 , arsenic - 74 , barium - 103 , barium - 140 , beryllium - 7 , bismuth - 206 , bismuth - 207 , cadmium - 109 , cadmium - 115m , calcium - 45 , cerium - 139 , cerium - 141 , cerium - 144 , cesium - 137 , chromium - 51 , cobalt - 55 , cobalt - 56 , cobalt - 57 , cobalt - 58 , cobalt - 60 , cobalt - 64 , copper - 67 , erbium - 169 , europium - 152 , gallium - 64 , gallium - 68 , gadolinium - 153 , gadolinium - 157 gold - 195 , gold - 199 , hafnium - 175 , hafnium - 175 - 181 , holmium - 166 , indium - 110 , indium - 111 , iridium - 192 , iron - 55 , iron - 59 , krypton - 85 , lead - 210 , manganese - 54 , mercury - 197 , mercury - 203 , molybdenum - 99 , neodymium - 147 , neptunium - 237 , nickel - 63 , niobium - 95 , osmium - 185 + 191 , palladium - 103 , platinum - 195m , praseodymium - 143 , promethium - 147 , protactinium - 233 , radium - 226 , rhenium - 186 , rhenium - 188 , rubidium - 86 , ruthenium - 103 , ruthenium - 106 , scandium - 44 , scandium - 46 , selenium - 75 , silver - 110m , silver - 111 , sodium - 22 , strontium - 85 , strontium - 89 , strontium - 90 , sulfur - 35 , tantalum - 182 , technetium - 99m , tellurium - 125 , tellurium - 132 , thallium - 204 , thorium - 228 , thorium - 232 , thallium - 170 , tin - 113 , tin - 114 , tin - 117m , titanium - 44 , tungsten - 185 , vanadium - 48 , vanadium - 49 , ytterbium - 169 , yttrium - 86 , yttrium - 88 , yttrium - 90 , yttrium - 91 , zinc - 65 , and zirconium - 95 . specifically , the chelating group can include more than one metallic radioisotope . more specifically , the detectable chelating group can include 2 to about 10 , 2 to about 8 , 2 to about 6 , or 2 to about 4 metallic radioisotopes . specifically , the non - metallic radionuclide can be a non - metallic paramagnetic atom ( e . g ., fluorine - 19 ); or a non - metallic positron emitting radionuclide ( e . g ., carbon - 11 , fluorine - 18 , iodine - 123 , or bromine - 76 ). specifically , the compounds of the present invention can include more than one non - metallic radioisotope . more specifically , the compounds of the present invention can include 2 to about 10 , 2 to about 8 , 2 to about 6 , or 2 to about 4 non - metallic radioisotopes . a compound of formula ( i ), or a pharmaceutically acceptable salt thereof , can be administered to a mammal ( e . g ., human ) in conjunction with a chemotherapeutic agent , or a pharmaceutically acceptable salt thereof . accordingly , a compounds of formula ( i ) can be administered in conjunction with a chemotherapeutic agent to treat a tumor or cancer . as used herein , a “ chemotherapeutic agent ” is a compound that has biological activity against one or more forms of cancer and can be administered to a patient with a compound of formula ( i ) without losing its anticancer activity . suitable chemotherapeutic agents include , e . g ., antineoplasts . representative antineoplasts include , e . g ., adjuncts , androgen inhibitors , antibiotic derivatives , antiestrogens , antimetabolites , cytotoxic agents , hormones , immunomodulators , nitrogen mustard derivatives and steroids . physicians &# 39 ; desk reference , 50th edition , 1996 . representative adjuncts include , e . g ., levamisole , gallium nitrate , granisetron , sargramostim strontium - 89 chloride , filgrastim , pilocarpine , dexrazoxane , and ondansetron . physicians &# 39 ; desk reference , 50th edition , 1996 . representative androgen inhibitors include , e . g ., flutamide and leuprolide acetate . physicians &# 39 ; desk reference , 50th edition , 1996 . representative antibiotic derivatives include , e . g ., doxorubicin , bleomycin sulfate , daunorubicin , dactinomycin , and idarubicin . representative antiestrogens include , e . g ., tamoxifen citrate and analogs thereof . physicians &# 39 ; desk reference , 50th edition , 1996 . additional antiestrogens include nonsteroidal antiestrogens such as toremifene , droloxifene and roloxifene . magarian et al ., current medicinal chemistry , 1994 , vol . 1 , no . 1 . representative antimetabolites include , e . g ., fluorouracil , fludarabine phosphate , floxuridine , interferon alfa - 2b recombinant , methotrexate sodium , plicamycin , mercaptopurine , and thioguanine . physicians &# 39 ; desk reference , 50th edition , 1996 . representative cytotoxic agents include , e . g ., doxorubicin , carmustine [ bcnu ], lomustine [ ccnu ], cytarabine usp , cyclophosphamide , estramucine phosphate sodium , altretamine , hydroxyurea , ifosfamide , procarbazine , mitomycin , busulfan , cyclophosphamide , mitoxantrone , carboplati , cisplati , cisplatin , interferon alfa - 2a recombinant , paclitaxel , teniposide , and streptozoci . physicians &# 39 ; desk reference , 50th edition , 1996 . representative hormones include , e . g ., medroxyprogesterone acetate , estradiol , megestrol acetate , octreotide acetate , diethylstilbestrol diphosphate , testolactone , and goserelin acetate . physicians &# 39 ; desk reference , 50th edition , 1996 . representative immunodilators include , e . g ., aldesleukin . physicians &# 39 ; desk reference , 50th edition , 1996 . representative nitrogen mustard derivatives include , e . g ., melphalan , chlorambucil , mechlorethamine , and thiotepa . physicians &# 39 ; desk reference , 50th edition , 1996 . representative steroids include , e . g ., betamethasone sodium phosphate and betamethasone acetate . physicians &# 39 ; desk reference , 50th edition , 1996 . additional suitable chemotherapeutic agents include , e . g ., alkylating agents , antimitotic agents , plant alkaloids , biologicals , topoisomerase i inhibitors , topoisomerase ii inhibitors , synthetics , antiangiogenic drugs , and antibodies . see , e . g ., anticancer agents by mechanism , http :// www . dtp . nci . nih . gov / docs / cancer / searches / standard_mechanism_list . html , apr . 12 , 1999 ; approved anti - cancer agents , http :// www . ctep . info . nih . gov / handbook / handbooktext / fda_agen . htm , pages 1 – 7 , jun . 18 , 1999 ; mcmp 611 chemotherapeutic drugs to know , http // www . vet . purdue . edu / depts / bms / courses / mcmp611 / chrx / drg2no61 . html , jun . 24 , 1999 ; chemotherapy , http :// www . vetmed . lsu . edu / oncology / chemotherapy . htm , apr . 12 , 1999 ; and angiogenesis inhibitors in clinical trials , http :// www . cancertrials . nci . nih . gov / news / angio / table . html , pages 1 – 5 , apr . 19 , 2000 . representative alkylating agents include , e . g ., asaley , azq , bcnu , busulfan , bisulphan , carboxyphthalatoplatinum , cbdca , ccnu , chip , chlorambucil , chlorozotocin , cis - platinum , clomesone , cyanomorpholinodoxorubicin , cyclodisone , cyclophosphamide , dianhydrogalactitol , fluorodopan , hepsulfam , hycanthone , iphosphamide , melphalan , methyl ccnu , mitomycin c , mitozolamide , nitrogen mustard , pcnu , piperazine , piperazinedione , pipobroman , porfiromycin , spirohydantoin mustard , streptozotocin , teroxirone , tetraplatin , thiotepa , triethylenemelamine , uracil nitrogen mustard , and yoshi - 864 . anticancer agents by mechanism , http :// dtp . nci . nih . gov / docs / cancer / searches / standard_mechanism_list . html , apr . 12 , 1999 . representative antimitotic agents include , e . g ., allocolchicine , halichondrin b , colchicine , colchicine derivatives , dolastatin 10 , maytansine , rhizoxin , paclitaxel derivatives , paclitaxel , thiocolchicine , trityl cysteine , vinblastine sulfate , and vincristine sulfate . anticancer agents by mechanism , http :// dtp . nci . nih . gov / docs / cancer / searches / standard_mechanism_list . html , apr . 12 , 1999 . representative plant alkaloids include , e . g ., actinomycin d , bleomycin , l - asparaginase , idarubicin , vinblastine sulfate , vincristine sulfate , mitramycin , mitomycin , daunorubicin , vp - 16 - 213 , vm - 26 , navelbine and taxotere . approved anti - cancer agents , http :// ctep . info . nih . gov / handbook / handbooktext / fda_agent . htm , jun . 18 , 1999 . representative biologicals include , e . g ., alpha interferon , bcg , g - csf , gm - csf , and interleukin - 2 . approved anti - cancer agents , http :// ctep . info . nih . gov / handbook / handbooktext / fda_agent . htm , jun . 18 , 1999 . representative antiangiogenic drugs include e . g ., marimastat , ag3340 , col - 3 , neovastat , bms - 275291 , tnp - 470 , thalidomide , squalamine , combretastatin a - 4 prodrug , endostatin , su5416 , su6668 , interferon - alpha , anti - vegf antibody , emd121974 , cai , interleukin - 12 , and im862 . angiogenesis inhibitors in clinical trials , http :// www . cancertrials . nci . nih . gov / news / angio / table . html , pages 1 – 5 , apr . 19 , 2000 . representative topoisomerase i inhibitors include , e . g ., camptothecin , camptothecin derivatives , and morpholinodoxorubicin . anticancer agents by mechanism , http :// dtp . nci . nih . gov / docs / cancer / searches / standard_mechanism_list . html , apr . 12 , 1999 . additional biologicals include drugs designed to inhibit tumor vascularization , which is also known as tumor angiogenesis . these drugs can be potent antiangiogenic agents . additional biologicals include humanized antibodies to growth factors , for example , to her2 , signaling molecules and adhesion receptors . additional biologicals also include treatment with recombinant viruses and other means of gene therapy delivery , including for example , dna , oligonucleotides , rybozymes , and liposomes . representative topoisomerase ii inhibitors include , e . g ., mitoxantron , amonafide , m - amsa , anthrapyrazole derivatives , pyrazoloacridine , bisantrene hcl , daunorubicin , deoxydoxorubicin , menogaril , n , n - dibenzyl daunomycin , oxanthrazole , rubidazone , vm - 26 and vp - 16 . anticancer agents by mechanism , http :// dtp . nci . nih . gov / docs / cancer / searches / standard_mechanism_list . html , apr . 12 , 1999 . representative synthetics include , e . g ., hydroxyurea , procarbazine , o , p ′- ddd , dacarbazine , ccnu , bcnu , cis - diamminedichloroplatimun , mitoxantrone , cbdca , levamisole , hexamethylmelamine , all - trans retinoic acid , gliadel and porfimer sodium . approved anti - cancer agents , http :// ctep . info . nih . gov / handbook / handbooktext / fda_agen . htm , jun . 18 , 1999 . in cases where compounds are sufficiently basic or acidic to form stable nontoxic acid or base salts , administration of the compounds as salts may be appropriate . examples of pharmaceutically acceptable salts are organic acid addition salts formed with acids which form a physiological acceptable anion , for example , tosylate , methanesulfonate , acetate , citrate , malonate , tartarate , succinate , benzoate , ascorbate , a - ketoglutarate , and a - glycerophosphate . suitable inorganic salts may also be formed , including hydrochloride , sulfate , nitrate , bicarbonate , and carbonate salts . pharmaceutically acceptable salts may be obtained using standard procedures well known in the art , for example by reacting a sufficiently basic compound such as an amine with a suitable acid affording a physiologically acceptable anion . alkali metal ( e . g ., sodium , potassium or lithium ) or alkaline earth metal ( e . g ., calcium ) salts of carboxylic acids can also be made . the compounds of formula ( i ) can be formulated as pharmaceutical compositions and administered to a mammalian host , such as a human patient in a variety of forms adapted to the chosen route of administration , i . e ., orally or parenterally , by intravenous , intramuscular , topical or subcutaneous routes . thus , the present compounds may be systemically administered , e . g ., orally , in combination with a pharmaceutically acceptable vehicle such as an inert diluent or an assimilable edible carrier . they may be enclosed in hard or soft shell gelatin capsules , may be compressed into tablets , or may be incorporated directly with the food of the patient &# 39 ; s diet . for oral therapeutic administration , the active compound may be combined with one or more excipients and used in the form of ingestible tablets , buccal tablets , troches , capsules , elixirs , suspensions , syrups , wafers , and the like . such compositions and preparations should contain at least 0 . 1 % of active compound . the percentage of the compositions and preparations may , of course , be varied and may conveniently be between about 2 to about 60 % of the weight of a given unit dosage form . the amount of active compound in such therapeutically useful compositions is such that an effective dosage level will be obtained . the tablets , troches , pills , capsules , and the like may also contain the following : binders such as gum tragacanth , acacia , corn starch or gelatin ; excipients such as dicalcium phosphate ; a disintegrating agent such as corn starch , potato starch , alginic acid and the like ; a lubricant such as magnesium stearate ; and a sweetening agent such as sucrose , fructose , lactose or aspartame or a flavoring agent such as peppermint , oil of wintergreen , or cherry flavoring may be added . when the unit dosage form is a capsule , it may contain , in addition to materials of the above type , a liquid carrier , such as a vegetable oil or a polyethylene glycol . various other materials may be present as coatings or to otherwise modify the physical form of the solid unit dosage form . for instance , tablets , pills , or capsules may be coated with gelatin , wax , shellac or sugar and the like . a syrup or elixir may contain the active compound , sucrose or fructose as a sweetening agent , methyl and propylparabens as preservatives , a dye and flavoring such as cherry or orange flavor . of course , any material used in preparing any unit dosage form should be pharmaceutically acceptable and substantially non - toxic in the amounts employed . in addition , the active compound may be incorporated into sustained - release preparations and devices . the active compound may also be administered intravenously or intraperitoneally by infusion or injection . solutions of the active compound or its salts can be prepared in water , optionally mixed with a nontoxic surfactant . dispersions can also be prepared in glycerol , liquid polyethylene glycols , triacetin , and mixtures thereof and in oils . under ordinary conditions of storage and use , these preparations contain a preservative to prevent the growth of microorganisms . the pharmaceutical dosage forms suitable for injection or infusion can include sterile aqueous solutions or dispersions or sterile powders comprising the active ingredient which are adapted for the extemporaneous preparation of sterile injectable or infusible solutions or dispersions , optionally encapsulated in liposomes . in all cases , the ultimate dosage form should be sterile , fluid and stable under the conditions of manufacture and storage . the liquid carrier or vehicle can be a solvent or liquid dispersion medium comprising , for example , water , ethanol , a polyol ( e . g ., glycerol , propylene glycol , liquid polyethylene glycols , and the like ), vegetable oils , nontoxic glyceryl esters , and suitable mixtures thereof . the proper fluidity can be maintained , for example , by the formation of liposomes , by the maintenance of the required particle size in the case of dispersions or by the use of surfactants . the prevention of the action of microorganisms can be brought about by various antibacterial and antifungal agents , for example , parabens , chlorobutanol , phenol , sorbic acid , thimerosal , and the like . in many cases , it will be preferable to include isotonic agents , for example , sugars , buffers or sodium chloride . prolonged absorption of the injectable compositions can be brought about by the use in the compositions of agents delaying absorption , for example , aluminum monostearate and gelatin . sterile injectable solutions are prepared by incorporating the active compound in the required amount in the appropriate solvent with various of the other ingredients enumerated above , as required , followed by filter sterilization . in the case of sterile powders for the preparation of sterile injectable solutions , the preferred methods of preparation are vacuum drying and the freeze drying techniques , which yield a powder of the active ingredient plus any additional desired ingredient present in the previously sterile - filtered solutions . for topical administration , the present compounds may be applied in pure form , i . e ., when they are liquids . however , it will generally be desirable to administer them to the skin as compositions or formulations , in combination with a dermatologically acceptable carrier , which may be a solid or a liquid . useful solid carriers include finely divided solids such as talc , clay , microcrystalline cellulose , silica , alumina and the like . useful liquid carriers include water , alcohols or glycols or water - alcohol / glycol blends , in which the present compounds can be dissolved or dispersed at effective levels , optionally with the aid of non - toxic surfactants . adjuvants such as fragrances and additional antimicrobial agents can be added to optimize the properties for a given use . the resultant liquid compositions can be applied from absorbent pads , used to impregnate bandages and other dressings , or sprayed onto the affected area using pump - type or aerosol sprayers . thickeners such as synthetic polymers , fatty acids , fatty acid salts and esters , fatty alcohols , modified celluloses or modified mineral materials can also be employed with liquid carriers to form spreadable pastes , gels , ointments , soaps , and the like , for application directly to the skin of the user . examples of useful dermatological compositions which can be used to deliver the compounds of formula i to the skin are known to the art ; for example , see jacquet et al . ( u . s . pat . no . 4 , 608 , 392 ), geria ( u . s . pat . no . 4 , 992 , 478 ), smith et al . ( u . s . pat . no . 4 , 559 , 157 ) and wortzman ( u . s . pat . no . 4 , 820 , 508 ). useful dosages of the compounds of formula i can be determined by comparing their in vitro activity , and in vivo activity in animal models . methods for the extrapolation of effective dosages in mice , and other animals , to humans are known to the art ; for example , see u . s . pat . no . 4 , 938 , 949 . generally , the concentration of the compound ( s ) of formula i in a liquid composition , such as a lotion , will be from about 0 . 1 – 25 wt -%, preferably from about 0 . 5 – 10 wt -%. the concentration in a semi - solid or solid composition such as a gel or a powder will be about 0 . 1 – 5 wt -%, preferably about 0 . 5 – 2 . 5 wt -%. the amount of the compound , or an active salt or derivative thereof , required for use in treatment will vary not only with the particular salt selected but also with the route of administration , the nature of the condition being treated and the age and condition of the patient and will be ultimately at the discretion of the attendant physician or clinician . in general , however , a suitable dose will be in the range of from about 0 . 5 to about 100 mg / kg , e . g ., from about 10 to about 75 mg / kg of body weight per day , such as 3 to about 50 mg per kilogram body weight of the recipient per day , preferably in the range of 6 to 90 mg / kg / day , most preferably in the range of 15 to 60 mg / kg / day . the compound is conveniently administered in unit dosage form ; for example , containing 5 to 1000 mg , conveniently 10 to 750 mg , most conveniently , 50 to 500 mg of active ingredient per unit dosage form . ideally , the active ingredient should be administered to achieve peak plasma concentrations of the active compound of from about 0 . 5 to about 75 μm , preferably , about 1 to 50 μm , most preferably , about 2 to about 30 μm . this may be achieved , for example , by the intravenous injection of a 0 . 05 to 5 % solution of the active ingredient , optionally in saline , or orally administered as a bolus containing about 1 – 100 mg of the active ingredient . desirable blood levels may be maintained by continuous infusion to provide about 0 . 01 – 5 . 0 mg / kg / hr or by intermittent infusions containing about 0 . 4 – 15 mg / kg of the active ingredient ( s ). the desired dose may conveniently be presented in a single dose or as divided doses administered at appropriate intervals , for example , as two , three , four or more sub - doses per day . the sub - dose itself may be further divided , e . g ., into a number of discrete loosely spaced administrations ; such as multiple inhalations from an insufflator or by application of a plurality of drops into the eye . the ability of a compound of the invention to act as an mmp inhibitor may be determined using pharmacological models which are well known to the art , or using the methods described hereinbelow . the enzymatic activity of mmp - 2 , mmp - 9 , and mmp - 7 was monitored with the fluorescence quenched substrate mocacplgla 2 pr ( dnp )- ar - nh 2 . fluorescence was measured with a photon technology international ( pti ) spectrofluorometer interfaced to a pentium computer , equipped with the ratiomaster ™ and felix ™ hardware and software , respectively . the cuvette compartment was thermostated at 25 . 0 ° c . substrate hydrolysis was monitored at emission and excitation wavelengths of 328 and 393 nm and excitation and emission band passes of 1 and 3 nm , respectively . fluorescence measurements were taken every 4 s . less than 10 % hydrolysis of the fluorogenic substrate was monitored , as described by knight . knight , c . g . methods enzymol . 1995 , 248 , 18 – 34 . stromelysin i enzymatic activity was monitored using the synthetic fluorogenic substrate mocacrpkpve - nva - wrk ( dnp )- nh 2 ( peptides international , louisville , ky .) at excitation and emission wavelengths of 325 and 393 nm and excitation and emission band passes of 1 and 3 nm , respectively . human pro - mmp - 2 , pro - mmp - 9 , timp - 1 and timp - 2 were expressed in hela s3 cells infected with the appropriate recombinant vaccinia viruses and were purified to homogeneity , as previously described . fridman , r . ; fuerst , t . r . ; bird , r . e . ; hoyhtya , m . ; oelkuct , m . ; kraus , s . ; komarek , d . ; liotta , l . a . ; berman , m . l . ; stetler - stevenson , w . g . j . biol . chem . 1992 , 267 , 15398 – 15405 . fridman , r . ; birs , r . e . ; hoyhtya , m . ; oelkuct , m . ; komarek , d . ; liang , c . m . ; berman , m . l . ; liotta , l . a . ; stetler - stevenson , w . g . ; fuerst , t . r . biochem . j . 1993 , 289 , 411 – 416 . pro - mmp - 2 , pro - mmp - 9 , timp - 1 and timp - 2 concentrations were determined using the extinction coefficients of 122 , 800 , 114 , 360 , 26 , 500 and 39 , 600 m − 1 cm − 1 , respectively . to obtain active mmp - 2 , pro - mmp - 2 ( 7 . 3 μm ) was incubated at 37 ° c . for 1 h with 1 mm p - aminophenylmercuric acetate ( apma ) ( dissolved in 200 mm tris ) in buffer c . the enzyme solution was dialyzed against buffer d at 4 ° c . to remove apma . active mmp - 9 was obtained by incubating pro - mmp - 9 ( 1 μm ) with heat - activated recombinant human stromelysin 1 ( 68 nm ) ( mmp - 3 , generously provided by dr . paul cannon , center for bone and joint research , palo alto , calif .) at 37 ° c ., for 2 . 5 h in buffer c . the resulting solution was subjected to gelatin - agarose chromatography to remove stromelysin 1 . mmp - 9 was eluted with buffer d containing 10 % dmso and dialyzed against the same buffer without dmso to remove the organic solvent . pro - mmp - 2 and pro - mmp - 9 activation reactions were monitored using the fluorescence quenched substrate mocacplgla 2 pr ( dnp )- ar - nh 2 ( peptides international , louisville , ky . ), as will be described below . the mmp - 2 and mmp - 9 concentrations were determined by titration with timp - 1 . progress curves were obtained by adding enzyme ( 0 . 5 – 2 nm ) to a mixture of fluorogenic substrate ( 5 – 7 μm ) and varying concentrations of inhibitor in buffer r containing 5 – 15 % dmso ( final volume 2 ml ), in acrylic cuvettes with stirring and monitoring the increase in fluorescence with time for 15 – 30 minutes . the progress curves were nonlinear least squares fitted to equation 1 ( muller - steffner , h . m ., malver , o ., hosie , l ., oppenheimer , n . j ., and schuber , f . j . biol . chem . 1992 , 267 , 9606 – 9611 . ): f = ν s t + i ( ν 0 − ν s )( 1 − exp (− kt ))/ k + f 0 ( 1 ) where ν 0 represents the initial rate , ν s , the steady state rate , k , the apparent first order rate constant characterizing the formation of the steady - state enzyme - inhibitor complex and f 0 , the initial fluorescence , using the program scientist ( micromath scientific software , salt lake city , utah ). the obtained k values , ν 0 and ν s were further analyzed according to equations 2 and 3 for a one - step association mechanism ( ν 0 − ν s )/ ν s =[ i ]/( k i ( 1 +[ s ]/ k m )) ( 3 ) intercept and slope values , obtained by linear regression of the k versus inhibitor concentration plot ( equation 2 ), yielded the association and dissociation rate constants k on and k off , respectively , and the inhibition constant k i ( k off / k on ). alternatively , k i was determined from the slope of the ( ν 0 − ν s )/ ν s νs [ i ] plot according to equation 3 . the dissociation rate constants were determined independently from the enzyme activity recovered after dilution of a pre - formed enzyme - inhibitor complex . to this end , typically 200 nm of enzyme was incubated with 1 μm of inhibitor for a sufficient time to reach equilibrium (& gt ; 45 min ) at 25 . 0 ° c . the complex was diluted into 2 ml of buffer r containing fluorogenic substrate ( 5 – 7 μm final concentration ) to a final enzyme concentration of 1 nm . recovery of enzyme activity was monitored for ˜ 30 min . the fluorescence versus time trace was fitted , using the program scientist , to equation 4 f = ν s t +( ν 0 − ν s )( 1 − exp (− k off ))/ k off + f 0 ( 4 ) where ν o represents the initial rate ( very small ), ν s , the rate observed when the e . i complex is completely dissociated and k off , the first order rate constant when the e . i dissociation . analysis for linear competitive inhibition was performed in the following manner . initial rates were obtained by adding enzyme ( 0 . 5 – 2 nm ) to a mixture of fluorogenic substrate ( 5 – 7 μm ) and varying concentrations of inhibitor in buffer r , containing 5 – 15 % dmso ( final volume 1 ml ) in semi - micro quartz cuvettes , and monitoring the increase in fluorescence with time for 5 – 10 minutes . the fluorescence versus time traces were fitted by linear regression analysis using felix ™. the initial rates were fitted to equation 5 ( segel , i . h . in : enzyme kinetics , wiley inc ., new york , 1975 , pp . 104 . ): v / v max = s /( k m ( 1 + i / k i )+ s ) ( 5 ) where v and v max represent the initial and maximal velocities , s and i , the substrate and inhibitor concentrations , respectively , k m the michaelis - menten constant for the substrate - enzyme reaction and k i the inhibition constant , using the program scientist . inhibitors 1 – 4 all bind with the active site of the mmps that were used in the study , with k i values of micromolar , or less , however , the behavior of inhibitor 1 was very different . inhibitor 1 showed a dual behavior . it served as a mechanism - based inhibitor with a partition ratio of 79 ± 10 ( i . e . k cat / k inact ) for mmp - 2 and 416 ± 63 for mmp - 9 . furthermore , it also behaved as a slow - binding inhibitor , for which the rate constants for the on - set of inhibition ( k on ) and recovery of activity from inhibition ( k off ) were evaluated ( table 1 ). it would appear that coordination of the thiirane with the zinc ion ( as seen in energy - minimized computational models ; fig1 ) would set in motion a conformational change , which is presumed from the slow - binding kinetic behavior . the kinetic data fit the model for slow - binding inhibition . morrison , j . f . adv . enzymol . 1988 , 61 , 201 – 301 . covalent modification of the enzymes results from this conformational change . inhibitor 1 was incubated with mmp - 2 to the point that less than 5 % activity remained . this inhibitor - enzyme complex was dialyzed over three days , which resulted in recovery of approximately 50 % of the activity . this observation is consistent with modification of the active site glu - 404 ( according to the numbering for human mmp - 2 ), via the formation of an ester bond , which is a relatively labile covalent linkage . the time - dependent loss of activity is not merely due to the slow - binding behavior . for instance , for a k off of 2 × 10 − 3 s − 1 ( the values are not very different from one another in table 1 ) the half time for recovery of activity ( t 1 / 2 ) is calculated at just under 6 min . the fact that 50 % of activity still did not recover after dialysis over three days strongly argues for the covalency of enzyme modification . selectivity in inhibition of gelatinases by inhibitor 1 was observed . its k i values are 13 . 9 ± 4 nm and 600 ± 200 nm for mmp - 2 and mmp - 9 , respectively . the corresponding k i values are elevated to the micromolar range for the other mmps , even for the case of mmp - 3 , which does show the slow - binding , mechanism - based inhibition profile . in addition , the values for k on are 611 - and 78 - fold larger for mmp - 2 and mmp - 9 , respectively , than that for mmp - 3 . whereas the k off values are more similar to one another , the value for mmp - 2 is the smallest , so the reversal of inhibition of this enzyme takes place more slowly . collectively , these kinetic parameters demonstrate that inhibitor 1 can be a potent and selective inhibitor for mmp - 2 , mmp - 9 , and especially mmp - 2 . it has been previously shown that two molecules of either timp - 1 or timp - 2 ( endogenous cellular protein inhibitors of mmps ) bind to activated mmp - 2 and mmp - 9 . olson , m . w . ; gervasi , d . c . ; mobashery , s . ; fridman , r . j . biol . chem . 1997 , 272 , 29975 . one binding event is high affinity and would appear physiologically relevant , whereas the second binding event takes place with relatively lower affinity ( micromolar ). olson , m . w . ; gervasi , d . c . ; mobashery , s . ; fridman , r . j . biol . chem . 1997 , 272 , 29975 . inhibition of mmp - 2 and mmp - 9 by timps also follows slow - binding kinetics . the kinetic parameters for these interactions at the high affinity site are listed in table 1 . the kinetic parameters for the slow - binding component of inhibition of mmp - 2 and mmp - 9 by inhibitor 1 ( k on and k off ) approach closely the same parameters for those of the protein inhibitors . olson , m . w . ; gervasi , d . c . ; mobashery , s . ; fridman , r . j . biol . chem . 1997 , 272 , 29975 – 29983 . oxiranes 4 – 6 inhibit mmps in a competitive manner with higher k i values . there was no evidence of slow - binding behavior or time - dependence of loss of activity with this inhibitor with any of the mmps . small - molecule inhibitor 1 follows both slow - binding and mechanism - based inhibition in its kinetic profile . this compound appears to behave very similarly to the endogenous cellular protein inhibitors for mmps ( timps ) in the slow - binding component of inhibition . furthermore , the inhibitor also exhibits a covalent mechanism - based behavior in inhibition of these enzymes . the high discrimination in targeting that inhibitor 1 displays ( both in affinities and the modes of inhibition ) among the other structurally similar mmps is noteworthy and could serve as a paradigm in the design of inhibitors for other closely related enzymes in the future . 1 h and 13 c nmr spectra were recorded on either a varian gemini - 300 , a varian mercury - 400 or a varian unity - 500 spectrometer . chemical shifts are reported in ppm from tetramethylsilane on the d scale . infrared spectra were recorded on a nicolet 680 dsp spectrophotometer . mass spectra were recorded on a kratos ms 80rft spectrometer . melting points were taken on an electrothermal melting point apparatus and are uncorrected . thin - layer chromatography was performed with whatman reagents 0 . 25 mm silica gel 60 - f plates . all other reagents were purchased from either aldrich chemical company or across organics . the following buffers were used in experiments with enzymes : buffer c ( 50 mm hepes at ph 7 . 5 , 150 mm nacl , 5 mm cacl 2 , 0 . 02 % brij - 35 ); buffer r ( 50 mm hepes at ph 7 . 5 , 150 mm nacl , 5 mm cacl 2 , 0 . 01 % brij - 35 , and 1 % v / v me 2 so ) and buffer d ( 50 mm tris at ph 7 . 5 , 150 mm nacl , 5 mm cacl 2 , and 0 . 02 % brij - 35 ). ( 4 - phenoxyphenylsulfonyl ) methyloxirane ( 4 ). to compound 11 ( 598 mg , 2 . 5 mmol ) in dichloromethane ( 10 ml ), mcpba ( 2 . 84 g , 10 mmol , aldrich 57 – 86 %), was slowly added . the mixture was stirred at room temperature for 3 days , after which time a second portion of mcpba ( 2 . 84 g , 10 mmol ) was added . the mixture was then stirred for another 4 days , after which time the mixture was poured into ethyl acetate ( 200 ml ), and washed with aqueous sodium thiosulfate ( 3 × 50 ml , 10 % w / v ), aqueous sodium bicarbonate ( 3 × 50 ml , 5 % w / v ), and brine ( 50 ml ). the organic phase was dried over magnesium sulfate and was concentrated to provide a yellow oil . the crude material was purified by column chromatography ( silica , 4 : 1 hexanes : ethyl acetate ) to give compound 4 as a pale yellow semi - solid ( 501 mg , 70 %). 1 h nmr ( 500 mhz , cdcl 3 ) d 7 . 90 – 7 . 86 ( m , 2 h ), 7 . 46 – 7 . 40 ( m , 2 h ), 7 . 26 – 7 . 22 ( m , 1 h ), 7 . 10 – 6 . 96 ( m , 4 h ), 3 . 34 – 3 . 24 ( m , 2 h ), 2 . 84 – 2 . 8 ( m , 1 h ), 2 . 49 – 2 . 46 ( m , 1 h ); 13 c nmr ( 125 mhz , cdcl 3 ) d 163 . 15 , 154 . 95 , 130 . 76 , 130 . 51 , 125 . 52 , 120 . 77 , 117 . 83 , 59 . 89 , 46 . 13 ; ir ( film ) 3054 ( w ), 2919 ( w ), 1576 ( s ), 1492 ( s ), 1320 ( s ), 1245 ( s ), 1148 ( s ) cm − 1 ; m / z ( ei ) 290 ( m + , 100 %), 233 ( 70 ) ( 50 ), 185 ( 40 ); hrms ( ei ) calcd . for c 15 h 14 o 4 s 290 . 0613 , found 290 . 0611 . ( a .) o - 4 - phenoxyphenyl - n , n - dimethylthiocarbamate ( 8 ). to a solution of 4 - phenoxyphenol ( 7 , 8 . 46 g , 45 mmol ) in dmf ( 40 ml ) at 10 cc , sodium hydride ( 1 . 83 g , 45 mmol , 60 % dispersion in mineral oil ) was added in small portions . after the evolution of hydrogen ceased , n , n - dimethylthiocarbamoyl chloride ( 6 . 16 g , 50 mmol ) was added in one portion . the reaction mixture was then stirred at 70 cc for 2 hours . the mixture was cooled to room temperature , poured into water ( 100 ml ) and extracted with chloroform ( 3 × 50 ml ). the combined organic extracts were washed with aqueous potassium hydroxide ( 50 ml , 5 % w / v ), and brine ( 10 × 50 ml ). the organic extract was dried over magnesium sulfate and concentrated to obtain a yellow oil . the crude material was purified by column chromatography ( silica , 5 : 1 hexanes : ethyl acetate ) to give compound 8 as a white solid ( 11 . 16 g , 90 %). m . p . 50 – 51 cc ; 1 h nmr ( 300 mhz , cdcl 3 ) d 7 . 38 – 7 . 31 ( m , 2 h ), 7 . 14 – 7 . 08 ( m , 1 h ), 7 . 06 – 7 . 00 ( m , 6 h ), 3 . 46 ( s , 3 h ), 3 . 34 ( s , 3 h ); 13 c nmr ( 75 mhz , cdcl 3 ) d 188 . 17 , 157 . 26 , 155 . 16 , 149 . 62 , 130 . 05 , 124 . 11 , 123 . 71 , 119 . 31 , 43 . 57 , 38 . 96 ; ir ( kbr ) 3040 ( m ), 2938 ( s ), 1587 ( s ), 1487 ( s ), 1394 ( s ), 1287 ( s ), 1190 ( s ) cm − 1 ; m / z ( ei ) 273 ( m + , 15 %), 186 ( 100 ); hrms ( ei ) calcd . for c 15 h 15 no 2 s 273 . 0823 , found 273 . 0824 . ( b .) s - 4 - phenoxyphenyl - n , n - dimethylthiocarbamate ( 9 ). compound 8 ( 3 . 99 g , 15 mmol ) was heated under argon at 260 cc for 3 . 5 hours . the resulting dark brown oil was purified by column chromatography using a gradient eluent system ( silica , 19 : 1 then 9 : 1 then 3 : 1 hexanes : ethyl acetate ) to obtain compound 9 as a pale yellow solid ( 2 . 55 g , 64 %). m . p . 97 – 99 cc ; 1 h nmr ( 400 mhz , cdcl 3 ) d 7 . 45 – 7 . 40 ( m , 2 h ), 7 . 40 – 7 . 30 ( m , 2 h ), 7 . 15 – 7 . 10 ( m , 1 h ), 7 . 05 ( d , j = 8 . 8 hz , 2 h ) 6 . 98 ( d , j = 8 . 8 hz , 2 h ) 3 . 08 ( bs , 3 h ), 3 . 02 ( bs , 3 h ); 13 c nmr ( 100 mhz , cdcl 3 ) d 167 . 48 , 158 . 87 , 156 . 53 , 137 . 66 , 130 . 09 , 124 . 14 , 122 . 39 , 119 . 87 , 118 . 94 , 37 . 14 ; ir ( kbr ) 3037 ( w ), 2925 ( w ), 1652 ( s ), 1581 ( s ) 1486 ( s ), 1239 ( s ) cm − 1 ; m / z ( ei ) 273 ( m + , 25 %), 257 ( 5 ), 200 ( 5 ); hrms ( ei ) calcd . for c 15 h 15 no 2 s 273 . 0823 , found 273 . 0822 . ( c .) 4 - phenoxythiophenol ( 10 ). a mixture of compound 9 ( 2 . 55 g , 9 mmol ) in methanol ( 20 ml ), and aqueous naoh ( 10 ml , 10 % w / v ), were refluxed for 4 hours . the solution was cooled to room temperature and was acidified to ph 1 with aqueous hcl ( 1m ). water ( 100 ml ) was added and the mixture was extracted with chloroform ( 3 × 50 ml ). the combined organic extracts were washed with brine ( 50 ml ), dried over magnesium sulfate and concentrated to obtain a yellow oil . the crude product was purified by column chromatography ( silica , 5 : 1 hexanes : ethyl acetate ) to give compound 10 as a pale yellow oil ( 1 . 80 g , & gt ; 99 %). 1 h nmr ( 300 mhz , cdcl 3 ) d 7 . 36 – 7 . 31 ( m , 2 h ), 7 . 30 – 7 . 25 ( m , 2 h ), 7 . 13 – 7 . 09 ( m , 1 h ), 7 . 04 – 6 . 88 ( m , 4 h ), 3 . 43 ( s , 1 h ); 13 c nmr ( 75 mhz , cdcl 3 ) d 157 . 30 , 156 . 15 , 132 . 14 , 130 . 00 , 124 . 04 , 123 . 95 , 119 . 88 , 119 . 04 ; ir ( film ) 3038 ( w ), 1583 ( s ), 1484 ( s ), 1236 ( s ), 1166 ( s ) cm − 1 ; m / z ( ei ) 202 ( m + , 100 %; hrms ( ei ) calcd . for c 12 h 10 os 202 . 0452 , found 202 . 0454 . ( d .) 3 -( 4 - phenoxyphenylsulfanyl )- 1 - propene ( 11 ). to a mixture of compound 10 ( 516 mg , 2 . 7 mmol ) and potassium carbonate ( 534 mg , 3 . 9 mmol ) in dmf ( 5 ml ), allyl bromide ( 253 μl , 2 . 9 mmol ) was added in one portion . the mixture was stirred at room temperature overnight . the crude reaction mixture was poured into ether ( 200 ml ), washed with saturated aqueous potassium carbonate ( 25 ml ), and brine ( 6 × 50 ml ). the organic layer was dried over magnesium sulfate and concentrated in vacuo to give a yellow oil . the crude material was purified by column chromatography ( silica , 98 : 2 hexanes : ethyl acetate ) to obtain the title compound as a pale yellow oil ( 598 mg , 93 %). 1 h nmr ( 300 mhz , cdcl 3 ) d 7 . 38 – 7 . 32 ( m , 4 h ), 7 . 15 – 7 . 10 ( m , 1 h ), 7 . 04 – 7 . 00 ( m , 2 h ), 6 . 97 – 6 . 92 ( m , 2 h ), 5 . 92 – 5 . 82 ( m , 1 h ), 5 . 10 – 5 . 04 ( m , 2 h ), 3 . 50 ( d , j = 7 . 2 hz , 2 h ); 13 c nmr ( 75 mhz , cdcl 3 ) d 157 . 14 , 156 . 73 , 134 . 01 , 133 . 22 , 130 . 05 , 129 . 50 , 123 . 75 , 119 . 40 , 119 . 25 , 117 . 81 , 38 . 84 ; ir ( film ) 3078 ( w ), 3039 ( w ), 1582 ( s ), 1484 ( s ), 1240 ( s ), 1165 ( s ) cm − 1 ; m / z ( ei ) 242 ( m + , 100 %), 201 ([ m - allyl ] + , 100 ); hrms ( ei ) calcd . for c 15 h 14 os 242 . 0765 , found 242 . 0764 . 2 -( 4 - phenoxyphenylsulfonyl ) ethyloxirane ( 5 ). the title compound was prepared in the same manner as described for 4 , with the exception that compound 12 was used in place of compound 11 , and the reaction time was 2 days . the title compound was obtained as a white solid ( 78 %). m . p . 75 – 77 cc ; 1 h nmr ( 500 mhz , cdcl 3 ) d 7 . 84 – 7 . 80 ( m , 2 h ), 7 . 44 – 7 . 38 ( m , 2 h ), 7 . 24 – 7 . 20 ( m , 1 h ), 7 . 09 – 7 . 04 ( m , 4 h ), 3 . 25 – 3 . 15 ( m , 2 h ), 3 . 02 – 2 . 97 ( m , 1 h ), 2 . 76 ( t , j = 4 . 3 hz , 1 h ), 2 . 49 ( dd , j = 3 . 0 and 5 . 0 hz , 1 h ), 2 . 19 – 2 . 10 ( m , 1 h ), 1 . 86 ( m , 1 h ); 13 c nmr ( 125 mhz , cdcl 3 ) d 162 . 93 , 155 . 02 , 130 . 58 , 130 . 81 , 125 . 47 , 120 . 69 , 117 . 91 , 53 . 15 , 50 . 32 , 47 . 29 , 26 . 23 ; ir ( kbr disc ) 3040 ( s ), 1580 ( s ), 1490 ( s ), 1320 ( s ), 1248 ( s ), 1148 cm − 1 ; m / z ( ei ) 304 ( m + , 80 %), 233 ( 50 ), 217 ( 100 ); hrms ( ei ) calcd . for c 16 h 16 o 4 s 304 . 0769 , found 304 . 0768 . ( a .) 4 -( 4 - phenoxyphenylsulfanyl )- 1 - butene ( 12 ). the title compound was prepared in the same manner as described for 11 , with the exception that 4 - bromo - 1 - butene was used in place of allyl bromide . compound 12 was obtained as a colorless oil ( 88 %). 1 h nmr ( 400 mhz , cdcl 3 ) d 7 . 37 – 7 . 32 ( m , 4 h ), 7 . 14 – 7 . 10 ( m , 1 h ), 7 . 04 – 7 . 00 ( m , 2 h ), 6 . 96 – 6 . 88 ( m , 2 h ), 5 . 90 – 5 . 80 ( m , 1 h ), 5 . 12 – 5 . 02 ( m , 2 h ), 2 . 98 ( m , 2 h ), 2 . 41 – 2 . 34 ( m , 2 h ); 13 c nmr ( 100 mhz , cdcl 3 ) d 157 . 18 , 156 . 50 , 136 . 65 , 132 . 57 , 130 . 05 , 123 . 72 , 119 . 55 , 119 . 21 , 116 . 47 , 34 . 65 , 33 . 71 ; ir ( film ) 3076 ( w ), 2923 ( w ), 1583 ( s ), 1485 ( s ), 1239 ( s ) cm − 1 ; m / z ( ei ) 256 ( m + , 100 %), 215 ([ m - allyl ] + , 90 ), 202 ( 15 ); hrms ( ei ) calcd . for c 16 h 16 os 256 . 0922 , found 256 . 0922 . 3 -( 4 - phenoxyphenylsulfonyl ) propyloxirane ( 6 ). the title compound was prepared in the same manner as described for 4 , with the exception that compound 13 was used in place of compound 11 , and that the reaction time was 3 days . the title compound was obtained as a white solid ( 94 %). 1 h nmr ( 500 mhz , cdcl 3 ) d 7 . 86 – 7 . 80 ( m , 2 h ), 7 . 44 – 7 . 39 ( m , 2 h ), 7 . 25 – 7 . 22 ( m , 1 h ), 7 . 10 – 7 . 04 ( m , 4 h ), 3 . 21 – 3 . 08 ( m , 2 h ), 2 . 90 – 2 . 86 ( m , 1 h ), 2 . 74 ( t , j = 4 . 5 hz , 1 h ), 2 . 45 ( dd , j = 2 . 5 and 4 . 5 hz 1 h ), 1 . 92 ( quin , j = 7 . 0 hz , 2 h ), 1 . 85 – 1 . 78 ( m , 1 h ), ( m , 1 h ); 13 c nmr ( 125 mhz , cdcl 3 ) d 162 . 84 , 155 . 08 , 130 . 58 , 130 . 48 , 125 . 43 , 120 . 70 , 117 . 88 , 56 . 28 , 51 . 64 , 46 . 86 , 31 . 17 , 20 . 12 ; ir ( kbr disc ) 3063 ( w ), 2923 ( w ), 1582 ( s ), 1488 ( s ), 1294 ( s ), 1246 ( s ), 1142 ( s ) cm − 1 ; m / z ( ei ) 318 ( m + , 40 %), 290 ( 20 ), 217 ( 100 %); hrms ( ei ) calcd . for c 17 h 18 o 4 s 318 . 0926 , found 318 . 0924 . ( a .) 5 -( 4 - phenoxyphenylsulfanyl )- 1 - pentene ( 13 ). the title compound was prepared in the same manner as described for 11 , with the exception that 5 - bromo - 1 - pentene was used in place of allyl bromide . the title compound was obtained as a colorless oil ( 65 %). 1 h nmr ( 500 mhz , cdcl 3 ) d 7 . 37 – 7 . 34 ( m , 4 h ), 7 . 13 – 7 . 09 ( m , 1 h ), 7 . 03 – 7 . 00 ( m , 2 h ), 6 . 96 – 93 ( m , 2 h ), 5 . 83 – 5 . 74 ( m , 1 h ), 5 . 06 – 4 . 98 ( m , 2 h ), 2 . 88 ( t , j = 7 . 0 hz , 2 h ), 2 . 22 – 2 . 16 ( m , 2 h ), 1 . 73 ( q , j = 7 . 0 hz , 2 h ); 13 c nmr ( 125 mhz , cdcl 3 ) d 157 . 23 , 156 . 36 , 137 . 84 , 132 . 30 , 130 . 41 , 130 . 03 , 123 . 67 , 119 . 55 , 119 . 16 , 115 . 62 , 34 . 61 , 32 . 86 , 28 . 61 ; ir ( film ) 3075 ( w ), 2929 ( m ), 1583 ( s ), 1484 ( s ), 1236 ( s ) cm − 1 ; m / z ( ei ) 270 ( m + , 100 %), 215 ( 70 ), 202 ( 60 ); hrms ( ei ) calcd . for c 17 h 18 os 270 . 1078 , found 270 . 1076 . ( 4 - phenoxyphenylsulfonyl ) methylthiirane ( 1 ). to a solution of compound 4 ( 710 mg , 2 . 5 mmol ) in thf ( 5 ml ), a solution of ammonium thiocyanate ( 559 mg , 7 . 4 mmol ) in water ( 3 ml ) was added . the reaction was stirred at room temperature for 16 hours , after which time it was poured into ethyl acetate ( 100 ml ), and then washed with water ( 25 ml ), followed by brine ( 25 ml ). the organic phase was dried over magnesium sulfate and was concentrated to give a white oil . the crude material was purified by column chromatography ( silica , 8 : 1 hexanes : ethyl acetate ) to obtain compound i as a white solid ( 102 mg , 14 %). m . p . 99 – 101 ° c . ; 1 h nmr ( 500 mhz , cdcl 3 ) d 7 . 89 – 7 . 84 ( m , 2 h ), 7 . 46 – 7 . 40 ( m , 2 h ), 7 . 26 – 7 . 22 ( m , 1 h ), 7 . 11 – 6 . 96 ( m , 4 h ), 3 . 52 ( dd , j = 5 . 5 and 14 . 5 hz , 1 h ), 3 . 17 ( dd , j = 7 . 5 and 14 . 5 hz , 1 h ), 3 . 09 – 3 . 03 ( m , 1 h ), 2 . 53 ( dd , j = 2 . 0 and 6 . 0 hz , 1 h ) 2 . 16 ( dd , j = 2 . 0 and 5 . 0 hz , 1 h ); 13 c nmr ( 125 mhz , cdcl 3 ) d 163 . 20 , 155 . 02 , 132 . 13 , 130 . 95 , 130 . 52 , 125 . 52 , 120 . 69 , 117 . 97 , 62 . 90 , 26 . 31 , 24 . 47 ; ir ( kbr disc ) 3030 ( w ), 1583 ( s ), 1486 ( s ), 1317 ( s ), 1246 ( s ), 1141 ( s ) cm − 1 ; m / z ( ei ) 306 ( m + , 2 %), 242 ([ m − so 2 ] + , 35 ); hrms ( ei ) calcd . for c 15 h 14 o 3 s 2 306 . 0384 , found 306 . 0382 . 2 -( 4 - phenoxyphenylsulfonyl ) ethylthiirane ( 2 ). the title compound was prepared in the same manner as described for 1 , with the exception that compound 5 was used in place of compound 4 . the crude material was purified by column chromatography ( silica , 2 : 1 hexanes : ethyl acetate ) to give the title compound as a white solid ( 93 %). m . p . 99 – 101 ° c . ; 1 h nmr ( 500 mhz , cdcl 3 ) d 7 . 83 ( d , j = 8 . 0 hz , 2 h ), 7 . 42 ( t , j = 8 . 0 hz , 2 h ), 7 . 26 – 7 . 22 ( m , 1 h ), 7 . 10 – 7 . 06 ( m , 4 h ), 3 . 30 – 3 – 20 ( m , 2 h ), 2 . 98 – 2 . 92 ( m , 1 h ), 2 . 52 ( dd , j = 1 and 6 hz , 1 h ), 2 . 48 – 2 . 39 ( m , 1 h ), 2 . 18 ( dd , j = 1 and 5 hz , 1 h ), 1 . 78 – 1 . 69 ( m , 1 h ); 13 c nmr ( 125 mhz , cdcl 3 ) d 162 . 94 , 155 . 03 , 132 . 50 , 130 . 55 , 130 . 51 , 125 . 48 , 120 . 71 , 117 . 92 , 55 . 97 , 33 . 62 , 29 . 82 , 26 . 05 ; ir ( kbr disc ) 3040 ( w ), 1583 ( s ), 1487 ( s ), 1256 ( s ), 1142 ( s ) cm − 1 ; m / z ( ei ) 320 ( m + , 50 %), 288 ( 20 ), 234 ( 40 ), 217 ( 60 ), 170 ( 100 ); hrms ( ei ) calcd . for c 16 h 16 o 3 s 2 320 . 0541 , found 320 . 0540 . 3 -( 4 - phenoxyphenylsulfonyl ) propylthiirane ( 3 ). the title compound was prepared in the same manner as described for 1 , with the exception that compound 6 was used in place of compound 4 . the crude material was purified by column chromatography ( silica , 2 : 1 hexanes : ethyl acetate ) to give the title compound as a white solid ( 85 %). m . p . 75 – 76 cc ; 1 h nmr ( 500 mhz , cdcl 3 ) d 7 . 85 – 7 . 82 ( m , 2 h ), 7 . 44 – 7 . 40 ( m , 2 h ), 7 . 26 – 7 . 22 ( m , 1 h ), 7 . 10 – 7 . 06 ( m , 4 h ), 3 . 20 – 3 . 09 ( m , 2 h ), 2 . 84 – 2 . 79 ( m , 1 h ), 2 . 50 ( dd , j = 1 and 6 hz , 1 h ), 2 . 14 ( dd , j = 1 and 5 . 5 hz , 1 h ), 2 . 12 – 2 . 06 ( m , 1 h ), 1 . 97 ( quin , j = 8 hz , 2 h ), 1 . 45 – 1 . 38 ( m , 1 h ); 13 c nmr ( 125 mhz , cdcl 3 ) d 162 . 85 , 155 . 08 , 132 . 55 , 130 . 60 , 130 . 49 , 125 . 43 , 120 . 69 , 117 . 91 , 56 . 09 , 35 . 13 , 34 . 86 , 25 . 72 , 22 . 92 ; ir ( kbr disc ) 3000 ( w ), 1583 ( s ), 1480 ( s ), 1254 ( s ), 1143 ( s ) cm − 1 ; m / z ( ei ) 334 ( m + , 30 %), 301 ( 10 ), 234 ( 100 ), 217 ( 70 ), 170 ( 70 ); hrms ( ei ) calcd . for c 17 h 18 o 3 s 2 334 . 0697 , found 334 . 06 . all publications , patents , and patent documents are incorporated by reference herein , as though individually incorporated by reference . the invention has been described with reference to various specific and preferred embodiments and techniques . however , it should be understood that many variations and modifications may be made while remaining within the spirit and scope of the invention . in addition , some references were obtained on the world wide web ( www ). these references are also incorporated by reference herein , as though individually incorporated by reference .	2
the present invention is directed to apparatus for synchronizing brake light activation of following vehicles using a rear - facing directional transmitter that is powered upon vehicle brake light activation . a following vehicle would pick up a signal from the transmitter , immediately re - transmitting it to the next following vehicle , simultaneously initiating brake light operation of that vehicle , and so on , thereby eliminating the one - second reaction delay of each successively following driver . the transmitter - receiver range is preferably limited such as to 100 to 120 feet for eliminating interference from other vehicles . while pulsed infra red ( ir ) radiation , described below , is preferred as the presently most practical and lowest cost directional tansmitter - receiver implementation , the present invention is not necessarily limited to any particular range of radiation frequency . ir leds pulsed at a standard rate provide good range and freedom from interference from other vehicles . the radiation is invisible , and penetrates fog and rain better than normal brake lights . an ir detector on the following vehicle simultaneously activates ir leds on that vehicle and its brake lights . this means that all these vehicle brake lights would turn on at the same time or synchronize with the brake lights of the first vehicle . the result is that all the vehicles behind the first vehicle would brake only about one second later , the cumulative delays that normally cause many of the worst rear - end collisions being eliminated . drivers of vehicles not equipped with the invention would benefit by seeing brake lights a number of seconds earlier , depending on the number of equipped vehicles ahead . rather than pulse the ir leds continuously while the brake lights are on , the pulsed ir leds are preferably driven for one second , when the brake lights first come on , or when an ir signal from a leading vehicle is detected . this feature allows automatic turn - on of the brake lights of the following vehicle while limiting the possibility of reception by vehicles in other lanes , when many vehicles are so equipped . the ir leds typically have a narrow output angle of about 50 degrees , and typical ir detector diodes have an even narrower pickup angle . however , it is preferred that the detector diodes as well as the leds be shrouded for further decreasing the possibility of interference pickup from adjacent lanes . the detector and associated receiver electronics can be mounted inside the passenger compartment near the center mirror , detecting through the windshield for long - term clarity , cleanliness , and reliability . the output from the detector triggers a two second timer to turn on the brake lights until the driver reacts to press the brake pedal . if the driver chooses not to brake , then only a short flash will be seen . in that case , a next - following driver is not likely to react with braking , although a heightened state of alertness is likely to result . with reference to fig1 - 5 of the drawings , exemplary apparatus 10 of the present invention is installed on a vehicle 20 , the vehicle having a brake pedal 22 or equivalent operatively connected to a brake actuator 24 for applying vehicle brakes 26 , a brake light switch 28 activating a brake light 30 in a conventional manner upon and during application of the brakes . a rear - facing infrared ( ir ) transmitter 40 is connected to the brake lights , being activated in response to operation of the brake light switch 28 , for producing rearwardly directed radiation from the vehicle 20 when its brakes are applied . an ir receiver 60 is oriented for detecting like radiation from another vehicle that the vehicle 20 is following , the receiver 60 also being connected to the brake light switch of the vehicle 20 for activating the brake light 30 independently of operation of the brake actuator 24 . fig2 shows three of the vehicles , designated 20 a , 20 b , and 20 c , in a line , each of the vehicles 20 being equipped with counterparts of the apparatus 10 . the vehicles 20 a and 20 c are typical passenger automobiles , and vehicle 20 b is a van truck . the passenger vehicles 20 a and 20 c preferably have the ir receivers mounted behind the windshield , together with the rear - view mirror ( that of vehicle 20 c only being shown ), whereas the truck 20 b ( being taller ) has the receiver 60 mounted near the bottom of the windshield . the automobiles 20 a and 20 c preferably have the ir transmitters 40 mounted high , such as adjacent an upper stop light assembly , if present , whereas the truck 20 b has the ir transmitter 40 mounted relatively lower such as together with the stop light 30 as shown in fig2 , a high mounting being typically much higher than the height of automobiles . with particular reference to fig3 , the transmitter 40 includes a first power regulator 42 for powering a series - parallel ir led emitter array 44 , the regulator having a storage capacitor 46 . a second power regulator 48 feeds a pulse generator 50 that is enabled by a burst timer 51 for driving a solid - state switch 52 , periodically grounding the ir array at high repetition rate and low duty - cycle during an interval of approximately one second . preferably the emitter array 44 is provided with a shroud 54 for avoiding transmission of radiation to adjacent lanes . the shroud 64 is configured for reducing the radiation angle of the array ( or of the leds individually ) to approximately five degrees . suitable devices for the switch 52 include power mosfets having low rdson , one such commercially available device being irlz44n for switching up to 31 amps from 5 volt logic . a preferred pulse repetition rate is 1000 times per second , with a 10 , 20 , or 30 microsecond pulse width ( corresponding to a duty cycle of one , two , or three percent ), which allows a much higher pulse power output than is practical on a continuous basis . the longer pulse widths provide greater range and power , the modulation at the same time allowing the signal to be selectively detected , using a filter having a corresponding pass frequency ( 1 khz in this case ), thereby eliminating unwanted interference . this frequency ( 1 khz in this example ) would be the standard pulse repetition frequency , allowing every vehicle to be responsive to the braking transmissions of every other vehicle that is equipped with the present invention . this frequency also permits the receiver to achieve substantially instant brake light activation . the first and second power regulators 42 and 48 are preferably powered from the brake light switch 28 for wiring simplicity , the first regulator 42 being current - limited such as to approximately 3 a for limiting inrush current to the storage capacitor 46 , which is preferably of large value such as 10 , 000 μf , for high - current pulse drive of the emitter array 44 as described above . once the capacitor is charged , the average current drawn at 12v is far less than the peak current powering the leds for only 10 microseconds . the first power regulator preferably is set for approximately 10v , with current limiting to approximately 3 a . the second regulator 48 can be a conventional voltage regulator , preferably set for 5v , a convenient operating voltage for the pulse generator 50 which can be a suitable 74 - series integrated circuit , the regulator 48 having a relatively lower current rating such as 100 ma . initial charging of the storage capacitor 46 , with current limiting in the first power regulator 42 as described above , does result in a slight delay in achieving full power output of the ir leds 44 ; however , this delay is relatively negligible , on the order of 5 ms . the burst timer 51 is configured for disabling the pulse generator 50 after a suitable period such as one second , for decreasing the possibility of spurious reception by other vehicles equipped with the present invention that are in adjacent lanes . the burst timer 51 can be implemented conveniently in a known manner based on capacitive discharge or using a pulse counter . fig4 shows an exemplary configuration of the receiver 60 , including an ir sensor 61 and an associated preamplifier 62 and pulse amplifier 64 . more particularly , and as shown in fig5 , the ir sensor itself is preferably a pin ir photodiode having a peak response at 890 nm . the preamplifier 62 includes an integrated operational amplifier 621 which is powered from a conventional 5 - v regulator ( not shown ), and having a feedback inductor 623 , the amplifier being configured for removing 60 hz pickup from streetlights , etc . it was discovered that the feedback inductor 623 materially improves rejection of ambient light interference . preferably the ir sensor 61 is provided with a shroud 63 for excluding reception of radiation from adjacent lanes . the shroud 63 is configured for reducing the reception angle of the sensor to approximately five degrees . the received signal from the sensor 61 and preamplifier 62 , having a duration of approximately 10 μs as generated in the above - described exemplary configuration of the ir transmitter 40 , is capacitively coupled to a counterpart of the operational amplifier , designated 641 , of the pulse amplifier 64 as further shown in fig5 . a suitable integrated circuit for both operational amplifiers 621 and 641 is available as device mcp 6022 from a variety of sources . a suitable device for use as the ir sensor 61 is similarly available as pin photodiode el - pd333 - 2c / ho1 . 2 . the pulse amplifier 64 drives a ( 1 khz ) bandpass filter 66 , preferably an active high - q filter for discriminating against spurious radiation . the filter 66 thus “ tunes ” the receiver to signals having a pulse repetition rate of 1 khz , thereby further eliminating interference . the resulting 1 khz sine wave is fed through a rectifying diode detector 67 and compared with a reference voltage in a comparator 68 for producing a logic signal which feeds a timer 70 for activating a lamp driver 72 , the output of which is connected to the brake light 30 . the timer 70 has an active duration of approximately two seconds ; consequently , the brake light is activated for that interval only , unless the interval is extended by operation of the vehicle brakes 26 . the apparatus 10 as described above has been tested , the results confirming an active range of approximately 75 feet . however , improved discrimination at the 1 khz signal frequency was found to be desirable . with further reference to fig6 , a preferred alternative configuration of the receiver , designated 60 ′, provides increased range and immunity from spurious signals . the receiver 60 ′ includes counterparts of the sensor 61 , preamplifier 62 , and of the pulse amplifier , designated 64 ′ ( having increased high - frequency gain ). the pulses , which are 10 μs in duration in the exemplary configuration of the ir transmitter 40 when a valid signal is being received , are directly fed to an inverted counterpart of the comparator , designated 68 ′, for passing pulses that exceed a predetermined amplitude greater than a noise amplitude . the comparator 68 ′ is connected to a schmitt trigger 69 , which triggers a counterpart of the timer , designated 70 ′ for producing corresponding pulses of uniform width being half the period of the pulse repetition rate of the ir transmitter 40 , that is 500 μs in the preferred exemplary configuration described above . thus , when radiation from the ir transmitter 40 of a leading vehicle is received , the output of the timer 71 is a 5v p - p square wave , at 1 khz in this example . the output of the timer 70 ′ is fed through an adjustable attenuator 74 to a counterpart of the ( high - q ) bandpass filter , designated 66 ′, producing an approximate sine wave output of robust amplitude only when fed at nearly exactly 1 khz . this output of the filter 66 ′ is passed through a counterpart of the diode detector 67 to a counterpart of the schmitt trigger , designated 69 ′, which activates a counterpart of the timer 70 that feeds a counterpart of the lamp driver 72 for activating the brake light 30 as described above . the apparatus 10 including the ir receiver 60 ′ as described above has also been tested , the results confirming an extended active range of approximately 100 feet , and with improved discrimination and noise immunity . with further reference to fig7 and 8 , another alternative configuration of the ir receiver , designated 60 ″, is responsive to vehicle speed for disabling operation below a predetermined speed such as 10 mph . the receiver 60 ″ includes counterparts of the ir sensor 61 , preamplifier 62 , pulse amplifier 64 ′, comparator 68 ′, schmitt trigger 69 , and the timer 70 ′. the receiver 60 ″ also includes counterparts of the adjustable attenuator 74 , band - pass filter 66 ′, diode detector 67 , schmitt trigger 69 ′, timer 70 , and the lamp driver 72 as described above for the receiver 60 ′. the timer 70 is enabled by a speed controller 78 that receives a vehicle speed signal from the vehicle 20 . under modern practice ( since 1985 ) typical vehicles no longer use traditional ( bowden ) speedometer cables , the speed timer being configured for receiving speedometer pulses having a 10 mph pulse rate of between 10 and 150 per second . thus the receiver 60 ″ is operative for activating the brake light 30 for 2 seconds in response to validly received ir signals unless the vehicle is traveling at or under approximately 10 mph . with further reference to fig9 and 10 , an alternative configuration of the apparatus , designated 10 ′ has a microprocessor implementation , which is consistent with recent developments in vehicle technology . the vehicle 20 , as is currently typical , includes one or more microprocessors ( not shown ) that communicate with vehicle components on a common signal bus 32 ( such as a canbus that is typically used in current vehicle manufacture ), a counterpart of the brake light switch , designated 28 ′, being activated by a brake light microprocessor 34 in response to signals on the signal bus 32 . the apparatus 10 ′ includes counterparts of the ir transmitter , designated 40 ′, and the ir receiver , designated 60 ′″, each being interfaced with the signal bus as described herein . the ir transmitter 40 ′ includes a transmit microprocessor 56 that is interfaced with the signal bus 52 , being programmed for driving the solid state switch 52 directly or , if necessary through a suitable buffer ( not shown ). the microprocessor 56 monitors the signal bus 32 for activation signals addressed to the brake light microprocessor , programmed activation of the solid state switch 52 being a series of pulses ( 10 μs in duration with a repetition rate of 1 khz and terminating after one second as described above in connection with the pulse generator 50 , or other suitable combination ), the pulses preferably terminating after one or two seconds as described above in connection with the burst timer 51 . a counterpart of the first power regulator , designated 42 ′, can be powered directly from a suitable switched battery bus , typically 12v , there being no particular advantage in powering from the vehicle brake light switch in this signal bus implementation of the apparatus 10 ′. also , since the regulator 42 ′ commences charging the bypass capacitor 46 as soon as the battery bus is switched on , there is no associated delay in activation of the emitter array 44 from the time the solid state switch 52 is first activated by the transmit microprocessor 56 . optionally , transmitter 40 ′ includes an auxiliary counterpart of the brake light switch , designated 28 ″, for driving an auxiliary counterpart of the brake light , designated 30 ′. the auxiliary brake light 30 ′ can be mounted together with the emitter array 44 . as described below , the auxiliary brake light 30 ′ can be operated in unison with the vehicle brake light 30 as described above or , for example , only when the emitter array is activated , the vehicle brake light 30 being conventionally activated only in response to application of the brakes 26 . alternatively , the auxiliary brake light 30 ′ can be activated both during brake application and activation of the emitter array , the vehicle brake light activation also being restricted to brake application . in another alternative , further described below , the transmit microprocessor 56 can be programmed for addressing the brake light microprocessor 34 and activating the vehicle brake light 30 during activation of the emitter array 44 , the brake light 30 also being conventionally activated during brake application . in this alternative the auxiliary brake light 30 ′ and associated auxiliary brake light switch 28 ″ can be omitted . the ir receiver 60 ′″ includes counterparts of the ir sensor 61 , the preamplifier 62 , the pulse amplifier 64 ′, the comparator 68 ′, the schmitt trigger 69 , and the timer 70 ′, the timer 70 ′ feeding a receive microprocessor 80 that is interfaced with the signal bus 32 . the microprocessor 80 is programmed for determining a validly received ir signal based on the pulse rate output of the schmitt trigger 69 , and addressing signals to the brake light microprocessor 34 for activating the brake light 30 , the signals continuing for a limited duration such as two seconds as described above . fig1 shows a brake light control process 100 for operating the vehicle brake lights when an ir signal of proper frequency is picked up by the receiver 60 ′″. in the process 100 , a brake output register b is initialized to zero ( turning brake lights off , unless vehicle brakes are on ). optionally , for implementations activating the auxiliary brake light 30 ′, a check loop is entered ( and reentered if the brake lights are already on ). next , a counter c is set to zero and then incremented by ir pulses during an interval of t milliseconds ( 100 , for example ). the resulting count is compared against low ( l ) and high ( h ) limits ( 95 and 105 , for example ) for validity . if valid , the register b is set for activating the brake lights and the process pauses for s milliseconds ( 2000 , for example ), after which control is returned to the beginning , resetting register b to zero to turn off the brake lights ( unless the brakes are applied ). the process 100 can be implemented in a microchip processor using a basic compiler such as picbasic pro , available from micro engineering labs , inc ., of colorado springs , colo . using the preferred ir pulse repetition rate of 1 khz with the count interval t being 100 ms , exemplary values for l and h , respectively , can be 96 and 94 ( 95 & lt ;= c & lt ;= 105 ), corresponding to a received pulse repetition rate range of 950 to 1050 hz . in this example , the receive microprocessor 80 takes 100 ms to identify the received ir pulse frequency ( thus giving a 100 ms reaction delay to each vehicle ), whereas the bandpass filter 66 ′ requires less than 10 ms . assuming the sample interval remains unchanged ( 1 ms ), there is a trade - off between speed and accuracy . for example , using a count duration of 10 ms , one count corresponds to 10 %, that is from 900 to 1100 hz . it will be understood that other count intervals between 10 ms and 100 ms can provide corresponding trade - offs between speed and accuracy . in practice , however , much higher count rates are possible using current technology , and ir pulse rates higher than 1 khz are contemplated within the scope of the present invention . as described above , the transmit microprocessor 56 is operative for activating the emitter array 44 in response to brake light activation signals on the signal bus , regardless of their origination from the receive microprocessor 80 or the vehicle braking system . alternatively , the receive microprocessor 80 can be implemented for addressing the transmit microprocessor exclusively , at least in configurations wherein the vehicle brake light is to be operated only in response to vehicle braking . although the present invention has been described in considerable detail with reference to certain preferred versions thereof , other versions are possible . for example , the enlargement structure 15 can be separately formed and bonded to the base portion 14 . also , a relay can be substituted for the solid state switch 52 , although a delay on the order of 10 ms would be introduced . therefore , the spirit and scope of the appended claims should not necessarily be limited to the description of the preferred versions contained herein .	1
referring first to fig1 an apparatus for removing electrostatic charges from paper according to the present invention comprises an enclosure 10 having a door 12 . in the presently preferred embodiment , enclosure 10 is roughly cubical with an edge length of about 36 inches . enclosure size and configuration can be changed as desired according to how large a stack is to be treated , as long as components inside of enclosure 10 to be described below are sufficiently removed from one another to prevent high voltage arcing effects . the door 12 has a handle 14 and hinges 16 and 18 . enclosure 10 may also be provided with a lid 20 for permitting access to the interior of enclosure 10 through its top . a separate enclosure 22 contains the means for applying a high voltage gradient to a stack of paper placed within enclosure 10 . it will be obvious to one skilled in the art that any suitable commercially available high voltage power supply with or without incorporated switches and meters will suffice for this application . in the presently preferred embodiment , the enclosure 22 contains a high voltage supply 24 having an off / on switch 26 , indicator light 28 , and power fuse 30 . high voltage supply 24 also incorporates a voltage adjustment dial 32 , voltmeter polarity switch 35 , and an overload fuse 36 . the system output polarity is not affected by the switch on the front panel , although the polarity may be changed internally by connector reversal . a volt meter 38 and a milliammeter 40 are also incorporated into high voltage supply 24 . the high voltage supply used in the presently preferred embodiment has an operating range of 0 - 60 kv . above 60 kv the corona discharge is very difficult to contain , or control . also contained in enclosure 22 is high voltage supply timer control 42 which controls line power ( 115 vac ) to high voltage supply 24 . timer control 42 has a center dial 43 having an inner part 44 and outer part 46 . depression of center part 44 activates power supply 24 for an interval of time preselected by means of outer part 46 . in the presently preferred embodiment , timer control 42 is a sixteen minute maximum range timer settable in one - half minute intervals . an indicator lamp 47 indicates operation of timer control 42 . turning now to fig2 the interior elements of enclosure 10 can now be seen . specifically , it can be seen that the walls of enclosure 10 are of two layers , an exterior layer 48 and an interior layer 50 . exterior layer 48 is made of insulating material . the preferred embodiment uses one - half inch plywood . interior layer 50 is made of a conducting material such as sheet aluminum . one skilled in the art will readily appreciate that the entire enclosure may be fabricated from aluminum or other conductive metal , although this would be more costly than the choice of materials in the presently preferred embodiment . also in fig2 one can see lid 20 drawn in phantom in a partially opened position . lid 20 has attached to it hooks 52 , which hook into eyelets 54 disposed in the interior of enclosure 10 . also inside enclosure 10 is treatment platform 56 . in the presently preferred embodiment , treatment platform 56 is an electrically conductive plate measuring about 18 × 18 × 1 / 8 inches . this plate may be of any desirable size as long as its edges are sufficiently distant from the interior of enclosure 10 . also , the edges of treatment platform 56 must be rounded to reduce high voltage arcing effects . treatment platform 56 is supported by four insulating posts 58 . the insulating posts 58 in the presently preferred embodiment are comprised of ceramic and are about 71 / 2 inches high . their height is selected to prevent arcing between treatment platform 56 and the floor or enclosure 10 . enclosure 10 also contains door actuated roller mechanism 60 . door actuator roller mechanism 60 is comprised of a pivot 62 , on which turns arms 64 and 66 and shorting arm 68 . arm 64 is provided with roller 70 which frictionally engages door 12 . arm 66 is attached to spring 72 which is also connected to the interior of enclosure 10 . spring 72 tends to pull the end of arm 66 remote from pivot 62 towards the interior of enclosure 10 . shorting arm 68 bears a high voltage cable 69 . arms 64 and 66 and shorting arm 68 are rigidly interconnected so that shorting arm 68 does not contact treatment platform 56 when door 12 is closed , but places cable 69 in contact with platform 56 when door 12 is open . cable 69 is electrically connected to resistor 74 , which is disposed in the interior of enclosure 10 on insulating posts 76 . the other end of resistor 74 is connected to ground . platform 56 is connected to the high voltage supply through coaxial cable 78 . the sheathing of coaxial cable 78 is connected at one end to the interior 50 of enclosure 10 and at the other end to ground . the center conductor of coaxial cable 78 is guided to treatment platform 56 through pipe 80 . pipe 80 is comprised of electrically insulative material . pipe 80 is secured to treatment platform 56 by an encircling outer circumference of the female pipe connector 82 . cable 78 is secured to the exterior of enclosure 10 by bracket 84 by wing nut means 92 electrically connected to an internal shield by a through bolt 93 . a center conductor of coaxial cable 78 plugs into the inner circumference of copper pipe 82 . as seen in fig3 edges 87 and 89 of treatment platform 56 are provided with polyethylene sleeves 86 to prevent the effects of corona discharge . in the preferred embodiment , sleeves 86 are slit polyethylene tubing secured to edges 87 and 89 with a silicon - based adhesive . also visible in fig3 are microswitches 88 and 90 which are open when door 12 is open and closed when door 12 is closed . electrically , these microswitches are interposed between timer control 42 and high voltage supply 24 . also visible in fig3 are magnetic door latches 92 . the electrical connection between various components is most readily perceived in fig4 . a line voltage source 94 is connected to timer control 42 through on / off switch 26 , to indicator lamp 28 , and fuse 30 . timer control 42 is connected to the adjustable high voltage supply 24 through microswitches 90 and 88 . high voltage supply 24 is connected to treatment platform 56 through fuse 36 , milliammeter 40 , and coaxial cable 78 . polarity and magnitude control 25 , controlled by voltage adjustment dial 32 , and polarity switch 35 in fig1 is connected to high voltage supply 24 . high voltage meter 38 is connected in parallel with treatment plate 56 . when switch 80 , corresponding to shorting arm 68 , is closed , treatment plate 56 is also connected to ground through resistor 74 . interior surfaces 50 of enclosure 10 are connected to ground and serve as both opposing electrodes and shield for platform 56 . in use , an apparatus for removing electrostatic charges from paper arranged in stacks according to the present invention operates as follows . door 12 is opened and the stack of papers is placed within enclosure 10 atop platform 56 , care being taken not to allow too much overlap of the plate 56 with the edges of the sheets [ the overlap cannot be great enough to permit breakdown of the dielectric -- paper -- and arcing to the inside of the enclosure ]. while door 12 is open , shorting arm 68 contacts it , thus draining off any charge which may reside on the plate due to previous charging operations . also , microswitches 88 and 90 are open thus disabling high voltage supply 24 and protecting the user from the hazard of electric shock . once the stack of papers has been properly positioned atop plate 56 , door 12 is closed . door 12 is retained in the closed position by magnetic latches 92 . closing door 12 closes microswitches 88 and 90 . then inner part 44 of center dial 43 of high voltage supply timer control 42 is depressed , thus activating high voltage supply 24 for a period of time preselected by use of outer part 46 . this time period depends on stack height and type of paper . to discharge the charges on an eight inch stack of computer form paper , for example , the stack is subjected to 55 kilovolts for four minutes . if a smaller stack is used , less time is required . after the preselected amount of time , high voltage timer control 42 deactivates high voltage supply 24 . the stack of paper is then removed , having been rendered more susceptible to manipulation in subsequent handling operations . although only one embodiment of the invention has been described in detail above , those skilled in the art will readily appreciate that many modifications are possible without departing from the novelty teachings and advantages of this invention . accordingly , all such modifications are intended to be included within the scope of this invention as defined by the following claims .	7
fig1 is a perspective exploded view of a first embodiment of the present invention . it shows a pressure bulkhead 1 having a longitudinal axis 17 . in this embodiment the bulkhead 1 has a circular or oval shape and comprises a frame 2 and a bulkhead main portion 3 . the bulkhead main portion 3 consists of a reticular component 5 , which is formed by a braided cloth 11 with a peripheral rim 12 . on the left side of the frame 2 there is an inside of a not shown interior of an aircraft , indicated by the reference sign a . reference sign b indicates an outside , e . g . the rear of the tail of the aircraft not shown . the frame 2 supports the bulkhead main portion 3 which is fixed to the frame 2 as shown in fig2 and in an enlarged sectional view in fig3 . fig2 ( above ) illustrates a plan view of the assembled bulkhead 1 from the inside a and from the outside b ( below ). as can be seen from fig2 , the cloth 11 is attached to the frame 2 from the outside b as illustrated in fig3 . fig3 is an enlarged schematic sectional view of an exemplary attachment of the bulkhead according to the first embodiment of fig1 to a fuselage 10 of the aircraft . in this example the frame 2 has a rectangle or cross - section or may have another cross - section and may be a hollow profile made of aluminium , such as aluminium 7150 . the cloth 11 is attached to the frame 2 on its surface facing to the outside b and on the outer peripheral surface facing to the fuselage 10 . the frame 2 is fixed to the fuselage 10 by first fixing elements 15 , e . g . rivets . for example , these rivets 15 may fix the attached cloth 11 as well . further and / or other methods for fixing the cloth 11 may be used , e . g . a suitable adhesive or the same . as can be seen from fig3 , the pressure bulkhead 1 is a flat element under unloaded condition . this is a significant advantage because the areas next to the bulkhead 1 are easy to access and to maintain . the cloth 11 may be made of braided ligament elements 6 as can be seen from fig4 in an enlarged view . the ligaments 6 are woven in a specific manner so that an airtight structure is achieved . thus , the cloth 11 will bear only tensional stresses under loaded condition , for example when the inside a ( see fig3 ) is under cabin pressure . in case of positive or negative pressure gradients , only tensional stresses will occur in the cloth 11 . furthermore , fig4 shows an opening 14 with so called polar weaves 13 in the cloth 11 . this type of opening may be used for airtight passage of e . g . conduits if necessary . the best position of such an arrangement can be found by finite elements analysis of the bulkhead . fig5 illustrates a standard cloth 11 with a circular shape . in an alternative embodiment the cloth 11 may comprise more than one layer of braided ligaments 6 . these layers may be standard fabrics stacked in a quasi orthotropic sequence . due to the airtight structure no resins or the like are necessary . therefore , the number of parts and time of manufacturing are significantly reduced . the cloth 11 may be made of aromatic polyamide fibres also known as aramide fibres . this material provides an excellent flame resistance and is a non toxic material . it has a functionality to ensure air tightness even if penetrated by a small particle ( e . g . shot bullet ). the examples shown in fig1 to 5 are of a diameter of approximately 4 m . fig6 is a perspective exploded view of a second embodiment of the present invention . it illustrates a pressure bulkhead 1 ′ having a longitudinal axis 17 . in this example , the bulkhead 1 has a circular or oval shape and comprises a frame 2 and a bulkhead main portion 3 . the bulkhead main portion 3 consists of two reticular components 5 ′ and 5 ″, which are formed by ligament elements 6 ′, 6 ″ in the shape of belts . on the left side of the frame 2 there is the inside , indicated by the reference sign a of a not shown interior of an aircraft . reference sign b indicates the outside , e . g . the rear part of the tail of the aircraft not shown . the frame 2 supports the bulkhead main portion 3 which is fixed to the frame 2 as shown in fig9 similar as shown in fig3 . the ligaments 6 ′ of the reticular component 5 ′ are arranged in a manner so that they extend radially in at least one first layer and one second layer , respectively and form at least two retaining layers for a sealing element 4 arranged between said retaining layers . the ligaments 6 ′ of the first retaining layer on the outside b are connected with inner ends 7 to a circular central belt 8 as can be seen from the right view of fig7 . the outer ends of the ligaments 6 ′ are connected to a peripheral belt 9 . these connections may be formed by sewing or the same . as shown in fig8 , the ligaments 6 ″ of the second retaining layer on the inside a may be smaller than the ligaments 6 ′ of the first layer due to the possible load they have to bear . these ligaments 6 ″ are connected together in a central region and are connected with their outer ends to the peripheral belt 9 as well as the sealing element 4 . according to this embodiment the sealing element 4 is made of a thermoplastic membrane which is flat under unloaded condition and retained by the ligaments 6 ′, 6 ″ of the retaining layers in case of loaded condition . the ligaments 6 ′, 6 ″ are loaded only by tensional stresses in both cases , positive and negative pressure gradients . the peripheral belt 9 and the ligaments 6 ′, 6 ″ and the sealing element 4 connected thereto is fixed to the fuselage 10 via the frame 2 for example as shown in fig9 . as can be seen from fig9 , the sealing element 4 and the ligaments 6 ′, 6 ″ are fixed to the frame 2 by second fixing element 16 , e . g . rivets . further and / or other fixing methods may be used . in the second embodiment of the present invention 250 ligaments 6 ′ and 4 ligaments 6 ″ are used for example . they form a flat bulkhead . regarding the sizing of the shown examples it has to be noted as follows : the dimension of each part has been obtained for a circular fuselage having a diameter of about 4 m . an analytical model of the ligaments 6 , 6 ′, 6 ″ based on the catenary &# 39 ; s equation has been used to evaluate the stability of the bulkhead . the load case taken into account is the maximum positive pressure gradient at ultimate level ( 2 δp = 1 . 234 bar ) that results the most critical one . all the results obtained , in terms of stress and strain , are compatible with the mechanical properties of the materials selected , while the resulting high frequencies of the first two modes of the frame ensure its stability at ultimate level . the results of this test show a maximum displacement of the bulkhead main portion 3 of the first embodiment of about 196 mm and of the second embodiment of about 453 mm . the present invention eliminates the disadvantages of the state of art mentioned above as follows . the pressure bulkhead 1 , 1 ′ is a flat element and has a less area with respect to a bulkhead with a single or double curvature . the pressure bulkhead 1 , 1 ′ has a reduced thickness and does not need any stiffeners . it cannot buckle because it is a membrane that exhibits only tensional stresses . for these reasons the weight is reduced and the manufacturing problems are reduced . furthermore , the pressure bulkhead 1 , 1 ′ does not need expensive curing cycles , so the manufacturing time is reduced . less material is needed with respect to the state of the art . the advantages are reduced thickness , no stiffeners , cost reduction and reduction of manufacturing time . it will be apparent that modifications can be made to the embodiments described above . for example , the cloth 11 may be soaked with an appropriate material to achieve a specific high level of air tightness . the pressure bulkhead 1 , 1 ′ may have an other shape than circular or oval shape . the ligaments 6 , 6 ′, 6 ″ may be made of materials with same or better characteristics than the mentioned ones .	1
in the lamp according to the invention , the synthetic resin member connects in radial directions , i . e . directions transverse to the axis of the lamp vessel , the end portion of the lamp vessel to the lamp cap . as a result , there is a comparatively large surface of application for the synthetic resin member to both the lamp vessel and the lamp cap . moreover , size differences in these components are more readily neutralized and the lamp cap can be more readily positioned correctly coaxially to the lamp vessel . the lamp vessel , the synthetic resin member and the lamp cap are then arranged substantially coaxially . the torsional strength of the connection between the lamp vessel and the lamp cap is materially improved as compared to the known lamp , due to the fact that the end portion of the lamp vessel is non - circular in cross - sections transverse to the axis of the lamp vessel . for example , the end portion may be oval or may have one or more depressions , for example transversal or axial grooves , in which the synthetic resin member adheres and which are filled with the synthetic resin . the end portion can have a projection which extends transversely to the axis of the lamp vessel and projects into the synthetic resin member . such a projection neutralizes shearing forces in the interface between the lamp cap and the synthetic resin member . the uniformity of the forces in this interface is larger when several , for example two or more , of such projections are distributed along the circumference of the end portion . such projections are readily obtained during the operation in which the end portion of the lamp vessel is shaped . this operation is a normal step in the manufacture of conventional lamps whose lamp vessel is fixed in the lamp cap by means of cement . the projections have a particular advantage , which will be stated hereinafter . the adhesion of the synthetic resin member to the material of the lamp cap , generally metal , for example copper alloys , such as copper - nickel , brass or tombak , stainless steel , aluminum , new silver or nickel - plated metals , is generally stronger than to glass of the lamp vessel . nevertheless , the inner surface of the lamp cap where it is in contact with the synthetic resin can be profiled to enlarge the application of the synthetic resin thereto . a good possibility is to use for this purpose an inwardly depressed metal lamp cap . the depression ( s ) is ( are ) then at least tangentially enclosed in the synthetic resin . in a particular embodiment of the lamp according to the invention , a current supply conductor to the light source is clamped between the synthetic resin and the sheath of the lamp cap . in lamp caps having a metal sheath , it has surprisingly been found that a good electrical contact between this sheath and this conductor is obtained . in fact it has been found that it is possible in this manner , for example with swan - s lamp caps , i . e . swan lamp caps having only one contact at the base portion and one contact at the sheath , and with edison lamp caps to connect the contact at the sheath of the lamp cap to a current supply conductor without using a soldering or welding operation . this means a very considerable simplification and acceleration of the manufacturing process , the more so as a current conductor emerging from the lamp over the edge of its cap can be situated at any point along the circumference of this edge . this is in contrast with a current conductor that can emerge from the base portion of the lamp cap only at one given area . therefore , before this current conductor can be fixed , it has first to be ascertained where this conductor is situated . another important advantage is that the relevant current supply conductor is now allowed to be so short that it does not emerge from the lamp cap . a loose wire outside the lamp cap , which may be touched in conventional lamps while it is alive , is not possible in this embodiment in which the current supply conductor remains inside the lamp cap . this embodiment renders welding or soldering of contacts entirely superfluous in lamps having two lamp caps each having a sheath contact , such as in a lamp having festoon caps . very satisfactory results are attained with at least substantially aromatic polyethersulphones , marketed under the tradename victrex by ici and having the structure of a repeating unit shown in fig6 of the drawings . the polyethersulphones may have a filling of mineral powders , such as sio 2 , caco 3 , mgo , zno , baso 4 , al 2 o 3 , but alternatively of fibres , such as glass fibres . the lamp according to the invention may be one of several kinds , for example an incandescent lamp , in which the light source is a filament . the filament may be surrounded by an inner bulb which is arranged in the lamp vessel . the lamp may alternatively be a discharge lamp , for example a low - pressure discharge lamp , such as a low - pressure mercury discharge lamp . the light source is in this case an ionizable mercury - containing gas with electrodes that may be arranged in the lamp vessel . inside the lamp vessel , the gas filling may be present in an inner bulb , such as in a low - pressure sodium discharge lamp . the lamp may alternatively be a high - pressure discharge lamp , such as a high - pressure sodium discharge lamp , which emits at least substantially white light . the light source is in this case a sodium - containing ionizable gas in a crystalline inner bulb provided with electrodes . the lamp according to the invention can be very readily manufactured . it has proved to be favorable to arrange a preformed ring of the polyethersulphone around the hot end portion of the lamp vessel . it is favourable to carry out this step while this end portion is still hot , for example has a temperature of 400 °- 450 ° c . due to the operation in which this portion is shaped . in an embodiment of the method , the ring is brought to an elevated temperature , for example 150 °- 200 ° c . the ring adheres , when it is provided , to the hot surface of the end portion . if desired , the ring around the end portion may then be shaped by means of a jig . the jig may have an elevated temperature , for example of 150 °- 200 ° c . subsequently , the lamp cap is provided . the lamp cap is heated for this purpose at a temperature of about 400 °- 450 ° c . the temperatures are not critical . at temperatures at the level of 400 ° c ., the synthetic resin material rapidly softens and adheres . at temperatures at the level of 200 ° c ., the ring retains its shape and does not adhere to objects with which it is in contact . on adhesion to objects at a temperature of about 400 ° c ., a connection is obtained which becomes stronger upon cooling . when a current supply conductor is bent around the ring provided on the end portion , an electrical connection is obtained with the lamp cap during the step of providing the lamp cap if this lamp cap has a metal sheath . these steps of connecting the cap and making an electrical contact require only a few , for example 3 to 4 seconds , while , when using a conventional cement , times of up to 25 seconds are required for curing the cement only . as a result , in conventional lamps , the step of mounting the lamp cap is one of the slowest assembling steps , so a material improvement is achieved by use of the invention . the ring of synthetic resin has in a favorable embodiment a conical shape , for example with an apic angle of 2 × 5 °. this shape facilitates the step of providing the ring around the end portion of the lamp vessel . in many cases , the lamp vessel is moreover conical at the free end of its end portion , because glass mouldings cannot be made with sharp shapes . one or more projections at the end portion of the lamp vessel are particularly favorable means for enlarging the grip of the synthetic resin on the lamp vessel . the ring of synthetic resin can then have at its inner surface one or more grooves , which are caused to engage these projections . a ring having a smaller wall thickness can be used while maintaining its enlarged grip if this ring has at its wide end one or more recesses with which the ring laterally engages a projection . these embodiments make it possible to provide the ring around the end portion in a simple manner , by slipping the ring onto the end portion while requiring only a small quantity of synthetic resin . similar recesses at the narrow end of the ring or grooves in the outer surface of the ring may be present to receive inward depressions in the lamp cap . eu ps 186 , 827 a2 discloses a lamp of pressed glass whose lamp cap is connected via a skirt of synthetic resin to the bottom of the lamp vessel . the sleeve then replaces a metal collar and a glass body through which in conventional lamps of pressed glass the bottom of the lamp vessel is connected to the lamp cap . the skirt of synthetic resin has a wide collar portion with longitudinal slots and internal nose - shaped projections , which under elastic deformation of the collar portion are caused to engage cavities in the bottom of the lamp vessel . as a result , a mechanical coupling is obtained between the lamp vessel and the skirt . at its outer surface the skirt has parts of screw - thread onto which the edison lamp cap is screwed , while it further has in its outer surface recesses in which the lamp cap is depressed in order to lock the screw connection between the skirt and the lamp cap against displacement . the skirt is consequently secured mechanically both to the lamp vessel and to the lamp cap . the skirt is more than a means for coupling the lamp vessel to the lamp cap . it is an insulator body between the lamp vessel and the lamp cap and a body which causes the length of the lamp to be considerably greater than in the case of a direct connection of the lamp cap to the lamp vessel . the synthetic resins that can be used for the sleeve include polyethersulphones . an embodiment of the lamp and the method according to the invention will be described more fully with reference to the drawing . as shown in fig3 this lamp has a translucent glass lamp vessel 1 having an axis 2 and an end portion 3 . a filament 4 serving as the light source is arranged in the lamp vessel 1 . in the lamp cap 5 , which has a sheath portion 6 and base portion 7 , the end portion 3 of the lamp vessel 1 is fixed by means of a thermoplastic synthetic resin member 8 so that the synthetic resin member adheres both to the lamp vessel and to the lamp cap . the lamp cap 5 has an electrical contact at the sheath 6 to which a current supply conductor 11 to the light source 4 is connected . a base contact 9 at the base portion 7 is connected to a second current supply conductor 12 to the light source 4 . as the thermoplastic synthetic resin use is made of polyethersulfone containing 30 % by weight of glass fibre . the synthetic resin member 8 bonds the end portion 3 of the lamp vessel 1 in directions transverse to the axis 2 of the lamp vessel 1 to this lamp vessel . the synthetic resin member 8 and the lamp cap 5 consequently surround the end portion 3 and the synthetic resin member 8 , respectively , substantially coaxially . the end portion 3 has non - circular cross - sections transverse to the axis 2 of the lamp vessel 1 in which the end portion 3 is in contact with the synthetic resin . in the embodiments shown in fig1 this non - circularity is due to a projection 10 which extends transversely to the axis 2 and projects into the synthetic resin member 8 ( fig5 ). although this is not visible in fig1 the end portion 3 has diametrically opposite to the projection 10 a second similar projection ( 14 in fig3 ). the projections 10 , 14 are distributed regularly along the circumference of end portion 3 . the current supply conductor 11 is in electrical contact with the lamp cap 5 on the inner side of this lamp cap due to the fact that this conductor 11 is clamped between the synthetic resin member 8 and the sheath portion 6 of the lamp cap 5 . the synthetic resin member 8 employed in the lamp of fig1 is a conical ring , the wide end of which is provided with two diametrically opposed recesses of which only one , 13 , is shown in fig2 a cross - sectional view of said ring . the synthetic resin employed in the member 8 is a polyethersulfone , the structural formula of a unit of which is shown in fig6 . steps in a method of mounting the lamp cap according to the invention will now be described with reference to fig1 fig2 and fig3 . in fig3 the lamp vessel 1 is shown rotated through 180 ° with respect to fig1 and is held in position by a holder 20 . the end portion 3 has a temperature of 400 ° to 450 ° c . due to a shaping and cleaning process , at the end of which process the lamp vessel 1 was sealed in a vacuum - tight manner by closing the exhaust tube 15 . a thermoplastic synthetic resin ring 8 heated at about 150 °- 200 ° c . is situated in a holder 21 accommodating heating elements 22 . the holders 20 , 21 are moved towards each other and the ring 8 is pressed on the end portion 3 , the ring melting at its inner surface and adhering to the end portion 3 . the recesses 13 in the ring 8 then engage the projections 10 , 14 . the ring consequently has a profile cooperating with the non - circular cross - sections of the end portion 3 . similar recesses may be present at the narrow end of the ring 8 in order to cooperate with depressions that may be present in the lamp cap 5 . a shaper 23 in fig4 which internally is oversized with respect to the interior of the lamp cap 5 , is moved to the holder 20 to shape the external surface of the thermoplastic synthetic resin ring 8 . after the current supply conductor 11 has been shortened and bent and the current supply conductor 12 has been aligned substantially coaxially , a holder 24 ( fig5 ) with a lamp cap 5 shown diagrammatically , which is heated by means of , for example , a flame to a temperature of about 400 ° to 450 ° c ., is pressed on the ring 8 , this ring melting at its outer surface and adhering to the sheath portion 6 ( shown in fig1 ) of the lamp cap 5 . after the holder 24 is removed , the connection of the base contact 9 ( shown in fig1 ) with the current supply conductor 12 can be made and the lamp may be cooled by means of an air jet . alternatively , the current supply conductor 11 may be shortened before the ring 8 is mounted in the step shown in fig3 .	7
the device of the present invention is generally adapted for use in an apparatus for measuring the concentration of analytes , such as alcohol , cholesterol , proteins , ketones , enzymes , phenylalanine , and glucose , in biological fluids such as blood , urine , and saliva . for brevity , we describe the details for using the device in connection with self - monitoring of blood glucose ; however , a person of ordinary skill in the art of medical diagnostics would be able to readily adapt the technology for measuring other analytes in other biological fluids . self - monitoring of blood glucose is generally done with meters that operate on one of two principles . the first is the photometric type , which is based on reagent strips that include a composition that changes color after blood is applied . the color change is a measure of the glucose concentration . the second type of blood glucose monitor is electrochemical and operates on the understanding that blood applied to an electrochemical cell can cause an electrical signal -- voltage , current , or charge , depending on the type of meter -- that can be related to the blood glucose concentration . the present invention permits convenient , remote dosing for both photometric and electrochemical systems . for brevity , the description below focuses on a photometric system . similar devices can be used with an electrochemical system . with either type of system , the present device permits the meter to monitor the complete course of the reaction , from the time the sample is applied until a glucose determination is made . the ability to measure the test start time makes it easier to determine the glucose concentration accurately . there are some advantages to using a photometric rather than an electrochemical system to make a glucose determination . one advantage of a photometric system is that measurements can be made at more than one wavelength of light , and corrections can be made for variations in blood hematocrit . the disposable disclosed here provides these advantages of the photometric system , while also permitting minimal meter contamination . the disposables used in photometric measurement systems are generally made in the form of a thin rectangular strip . the shape derives from the original so - called &# 34 ; dip and read &# 34 ; test strip configuration . one end serves as a handle , while the chemical reaction with the fluid sample is carried out at the other end . these rectangular disposables form the male portion of the interface with the meter . that is , the strip is retained by features on the meter that enclose the disposable . this method of retention invites contamination of the meter with the fluid sample . in order to avoid the problems of contamination the present disposable takes the form of a hollow frustum , which provides the female portion of the interface with the meter . that is , the disposable encloses a portion of the meter and serves as a cover to prevent contamination of the meter by the fluid sample . fig1 depicts in partial cutaway an embodiment of this invention in which the disposable 10 is a hollow frustum of a cone . membrane 12 is attached to the smaller end 14 . optional lip 16 provides a surface to which membrane 12 is attached with adhesive 18 . optional indentations 20 are spaced around the circumference of the cone to provide a retention mechanism , in conjunction with a groove on a meter . fig2 is a cross section of the disposable of fig1 taken along the line 2 -- 2 . as shown in fig2 the membrane is attached to the outside of the disposable . alternatively , as shown in fig1 , the membrane may be attached to the inside of the disposable . fig3 is an exploded perspective view of a photometric meter and a disposable device of the type shown in fig1 . meter 30 has an elongated configuration with a distal section 32 that is a substantially cylindrically symmetrical frustum , along whose perimeter is optionally a groove 34 . note that the disposable nests on the distal section of the meter in such a way that there is an accurately defined gap g between the distal end 36 of meter 30 and the bottom surface of membrane 12 . the accurate positioning contributes to measurement precision and reliability . in the cutout can be seen a light source 38 and detector 40 , which provide for illuminating a disposable and for detecting light reflected from the disposable , respectively . as discussed below , measuring light reflected from the disposable yields the glucose concentration in the sample applied to the membrane . although only one source and detector are shown in fig3 multiple sources , optionally having different output spectra , and / or multiple detectors may be used . fig4 is a perspective view of the way in which a device and meter of fig3 can be used to obtain a sample s from a stuck finger tip . it is quite easy for the user to bring the disposable into contact with the finger , which is a big advantage for users that have impaired vision . fig5 is a cross section of part of distal section 32 of meter 30 and disposable 10 , which illustrates the way indentations 20 and groove 34 positively locate meter 30 within disposable 10 , leaving gap g . note that gap g ensures that blood that penetrates through the membrane does not contaminate the meter . the gap dimension , while not critical , is preferably at least about 1 / 2 mm . an advantage of the device of the invention , when used with a meter of the type shown in fig3 is that the devices can be in a stack , nested conveniently in a container 42 , as shown in fig6 . a device can then be secured simply by inserting the distal section 32 of meter 30 into container 42 and engaging groove 34 and indentations 20 . after a test has been completed , a used disposable can be ejected into waste container w , as shown in fig7 provided there is an optional push - button ejection mechanism . push - button ejection mechanisms of the type that are widely known and used are suitable for this invention ( see e . g . ; u . s . pat . no . 3 , 991 , 617 ). one such mechanism is depicted in fig8 and 9 , which show a push - button mechanism mounted in a meter of the type shown in fig3 . the elements of the mechanism include shaft 44 , which joins ejector 46 and push button 48 . push button 48 works through shaft 44 to cause ejector 46 to disengage disposable 10 from the distal section 32 of meter 30 . spring 50 works to return the ejector 46 and push button 48 to their retracted position . push - button ejection , by permitting the disposable to be removed without direct contact , helps to avoid contamination . disposables to be used with push - button ejection mechanisms of the type shown in fig8 and 9 preferably have a flange 19 . fig1 depicts an embodiment of a meter of this invention , which includes a display 50 for depicting the analyte concentration measured by the meter . the display can be a light - emitting diode ( led ) display , a liquid crystal display ( lcd ), or similar display well known in the art . although the above description and figures contemplate a disposable having a circular cross section and meter having a distal section having a mating cross section , that geometry is not essential and , in fact , may not even be preferred . a primary consideration in selecting the geometry in a photometric system is the optical design . generally , reflectometry dictates at least a minimum angular separation ( typically 45 °) between a detector and specularly reflected light . this , in turn requires at least a minimum vertex angle of the conical disposable . however , it is an advantage to a user to be able to view his / her finger for dosing , and a large vertex angle interferes with that view . thus , a disposable having a rectangular cross section may be preferred , such as the hollow frustum of a rectangular pyramid 110 shown in fig1 . in that case , the angular separation between detector and specular - reflected light determines only the minimum feasible value of l , the longitudinal dimension of the larger open end . but the disposable could be smaller and provide less interference with a user &# 39 ; s view of his / her finger . furthermore , rectangular membranes can be fabricated from ribbons or sheets at less expense and with less waste of material . nevertheless , a circular cross section is advantageous when an array of several sources and / or detectors is used in the optical system . since contamination is possible if excess sample were to drop from the disposable , it is desirable to accommodate large samples , without dripping . various designs can serve to retain excess sample . one is shown in fig1 , 13 , and 14 . fig1 depicts the disposable of fig1 with indentations 124 on the small - end surface of the disposable . as shown in fig1 and 14 , the indentations allow capillary flow to fill the resulting gap between the membrane and the top inside surface of the device . an alternative way of forming such gaps is to adhere the membrane to the disposable with thick adhesive , leaving gaps to accommodate the excess sample . another way to absorb excess sample is to attach an absorbent pad 126 over the front surface of the membrane , as shown in fig1 . fig1 is an exploded perspective view of a meter and a disposable of the type shown in fig1 . the distal section 132 of meter 130 has an optional groove 134 , which is similar to groove 34 , for retaining the disposable . elongated neck 130 facilitates pickup of disposables from the elongated containers 42 shown in fig6 . display 150 depicts the measured analyte concentration . fig1 depicts an alternative embodiment of a meter adapted for use with the disposable of fig1 . fig1 depicts the distal portion of yet another embodiment of a disposable 210 and meter 230 . distal section 232 mates with disposable 210 . note that slots 234 are an alternative to groove 34 ( or 134 ) for capturing indentations , such as 220 , on the disposable . in the method of this invention , a blood sample is picked up on the outward - facing surface of the membrane . glucose in the sample interacts with a reagent in the membrane to cause a color change , which changes the reflectance of the inward - facing membrane surface . the light source in the meter illuminates the inward - facing membrane surface and measures the intensity of light reflected from that surface . using the appropriate computation , the change in reflectance yields the glucose concentration in the sample . a variety of combinations of membrane and reagent compositions are known for photometric determinations of blood glucose concentration . a preferred membrane / reagent composition is a polyamide matrix incorporating an oxidase enzyme , a peroxidase , and a dye or dye couple . the oxidase enzyme is preferably glucose oxidase . the peroxidase is preferably horseradish peroxidase . a preferred dye couple is 3 - methyl - 2 benzothiazolinone hydrazone hydrochloride plus 3 , 3 - dimethylaminobenzoic acid . details of that membrane / reagent combination and variations on it appear in u . s . pat . no . 5 , 304 , 468 , issued apr . 19 , 1994 , to phillips et al ., incorporated herein by reference . another preferred membrane / reagent composition is an anisotropic polysulfone membrane ( available from memtec america corp ., timonium , md .) incorporating glucose oxidase , horseradish peroxidase , and the dye couple 3 - methyl - 2 - benzothiazolinone hydrazone ! n - sulfonyl benzenesulfonate monosodium combined with 8 - anilino - 1 - naphthalene sulfonic acid ammonium . details of that membrane / reagent combination and variations on it appear in u . s . patent application ser . no . 08 / 302 , 575 , filed sep . 8 , 1994 , incorporated herein by reference . it will be understood by those skilled in the art that the foregoing descriptions of embodiments of this invention are illustrative of practicing the present invention but are in no way limiting . variations of the detail presented herein may be made without departing from the scope and spirit of the present invention .	8
in the preferred embodiment of the splash apron according to fig1 and 2 , the splash apron 1 is formed of straight , substantially vertical elongated , fibrous flaps or strips 2 , 3 , which are attached side - by - side in a row to a suitable supporting member 4 . the supporting member can further be attached by conventional methods behind the tire 5 , seen from the driving direction , to the frame structure or equivalent of a vehicle , which is not illustrated in the drawing . the fibrous flaps 33 of the splash apron are alternately long and short , respectively . the difference in length in comparison with the total length of the splash apron is not great , preferably about 5 - 15 %, which depends on the material to be used . advantageously the flaps 2 , 3 are manufactured of a flexible and facile , water - repellent artificial fiber material , which should be particularly resistant to corrosion . when a vehicle provided with the aforementioned splash aprons moves forwardly , the air flow separates the shorter and lighter flaps 3 from the longer and heavier flaps 2 , as is seen in fig3 . thus there are formed vertical air gaps in the splash apron . in the previous embodiment , the fibrous flaps can also be suitably divided into alternating groups of short and long flaps that is every other one of the flaps is short . the air gaps in the splash apron of the invention can also be created as shown in fig7 so that at the lower end of every second flap or group of flaps 10 there is attached a suitable leaden weight or equivalent 12 , in which case the lighter flaps 11 move more easily in accordance to the air flow . in the embodiment of fig1 - 3 the fibrous flaps of the splash apron fall directly downwardly from the supporting member . they can also be arranged to fall downwardly in a fan - shaped fashion , in which case the air gaps are arranged without any further measures between the flaps 2 , 3 of equal length . in fig4 is presented another splash apron according to the invention , which splash apron consists of adjacent ribbon - like or lamellated flaps 7 , 8 . every second flap 7 becomes wider in the downward direction from the supporting member 4 or its immediate neighbourhood , and respectively the remaining flaps 8 become narrower . owing to the effect of a driving draft , the flaps 7 which are wide at the bottom are bent backwardly and thus separated -- due to greater air resistance -- from the flaps 8 which are narrow at the bottom . thus the desired vertical or roughly vertical air gaps are formed in the splash apron . this is also due to the narrower web of the flaps 7 which connect the top of each flap to a common cross part as shown in fig4 . the splash apron of fig4 can also be realized so that the ribbon - like or lamellated flaps are partly arranged in overlapping or roughly adjacent fashion . in that case the first alternating flaps 8 , located partly at the front , could be of equal width , whereas the second alternating flaps 7 , located partly at the back , could still become wider towards the bottom . the splash apron is attached in a conventional fashion to a suitable supporting member , and by means of the member further behind the tire or directly to the body of the vehicle . in fig5 and 6 are illustrated details of a splash apron of the invention , where a certain type of supporting member is utilized . the fibrous , ribbon - like or lamellated flaps of the splash apron can be pressed in between the supporting pieces 41 , 42 by means of bolted joints 9 or similar joints . in the supporting pieces there are respectively arranged grooves 10 and brackets 11 to match those alternating flaps or groups of flaps , which are directed slightly backwardly from the plane of the splash apron ( fig6 ) in order to create or reinforce the air gaps . fig5 represents a side - elevation view of a similar point as described above , and fig6 represents a respective view for example at the next flap of the splash apron where the grooves and brackets do not exist and where the flap of the flash apron falls directly downwardly when in the resting position . the splash apron of the invention can be manufactured of any flexible and durable material , such as rubber or a suitable type of plastic . the whole of the splash apron can be made of one piece of material by suitably cutting the fibrous , ribbon - like or lamellated flaps therefrom and by leaving the upper part unbroken as is seen in fig4 . on the other hand , the flaps can also be manufactured separately , and what is more , of different materials . they can be arranged for instance so that every second flap is made of a more flexible material than the rest . in the above the present invention has been described with reference to a few preferred embodiments only . it is , however , by no means intended to limit the scope of the invention to include only these embodiments , but several modifications thereto are possible within the invention specified in the following patent claims .	1
the present invention provides a system which eliminates the need to isolate the gas purifier in the event of equipment malfunction or otherwise a false alarm . with reference to fig2 , a gas purifier 200 , which may be utilized in system 100 is provided . purifier 200 can be configured as a column , having a chemical adsorbent bed therein . a conventional purity gas stream such as nitrogen enters purifier 200 and is exposed to chemical adsorbent bed 210 , which removes contaminants such as hydrogen , carbon monoxide and oxygen . the chemical adsorbent can be made from nickel , palladium or any other material that is sensitive or selective to the impurities removed and retains same . the chemical adsorbent bed is designed to include at least one dual temperature sensor 204 , 205 , 206 that is located in close proximity to the adsorbent bed , but at various locations therein . the temperature sensors may be resistance - based devices , such as resistance temperature detectors ( rtds ) or thermocouples . these devices are inserted into the chemical adsorbent bed 210 through thermal wells , which are permanent tubular devices that project into the bed , and minimize the interference with the gas flow . the temperature sensors may also be located on the wall of the purifier bed . typically , more than one temperature sensor is utilized so that excessive temperature is quickly detected at the various locations within the bed . high chemical adsorbent temperatures are indicative of the bed being exposed to excessive contaminant levels . the temperature measured by sensors 204 , 205 , 206 is transformed into an electrical signal which is sent to a receiving computer card . in the event the computer registers a temperature in excess of the predetermined value , typically between 120 ° f . and 400 ° f ., adsorbent bed 210 is isolated by closing valves 220 , 230 , 240 , and the bed is vented to atmosphere or an abatement system ( not shown ) by opening valve 250 . the failure of temperature sensing equipment , such as thermocouples and thermocouple computer boards , generate an electrical signal that is similar in magnitude to that generated by a high temperature reading . therefore , the computer interprets failed temperature sensing equipment in the same manner as a high temperature reading , causing the purifier to shutdown as described above . such a shutdown is unnecessary , because the chemical adsorbent temperature is not excessive . the present invention addresses the need to distinguish between temperature sensing equipment failure and excessive chemical adsorbent temperature . in an exemplary embodiment , dual temperature sensor sets 204 a and 204 b ; 205 a and 205 b ; 206 a and 206 b ; can be utilized to detect the temperature at various locations in the bed . for example , one set of temperature sensors can be disposed in close proximity to the top of the purifier bed , while the others may be place near the center of the purifier , and in close proximity to the bottom of the purifier , respectively . utilizing dual temperature sensors in the manner explained below provides a means to distinguish a failure of the equipment ( i . e ., temperature sensor , computer card , etc .) from a real event such as temperature rise in the chemical adsorbent bed above a predetermined level . the latter would lead to the destruction of the chemical adsorbent , which could cause corrosive substances such as hydrochloric or sulfuric acid to be released from the purifier . without this distinction , gas purifier 200 would need to be shut down ( i . e ., taken off - line ) regardless of whether or not a real event were occurring . with continued reference to fig2 , conventional purity nitrogen is provided from an air separation unit 140 , or a backup source 160 to gas purifier 200 at near ambient temperature and a pressure ranging from about 10 psia to 200 psia , preferably 50 psia to 180 psia and most preferably 100 psia to 170 psia . the flow rate of the incoming stream ranges from ranging from 1 , 000 cfh - ntp to 1 , 000 , 000 cfh - ntp , preferably between 5 , 000 cfh - ntp and 750 , 000 cfh - ntp and most preferably between 10 , 000 cfh - ntp and 500 , 000 cfh - ntp , and contains between 0 . 1 and 10 part per million each of hydrogen , carbon monoxide and oxygen . the conventional purity nitrogen gas stream enters gas purifier 200 , and is passed through and exposed to the chemical adsorbent bed 210 . the adsorbent bed typically contains a nickel based chemical adsorbent . examples of other chemical adsorbents that can be employed include but not limited to palladium , zirconium , platinum , rhodium , ruthenium , and titanium - based or other materials that are selective toward particular contaminants . the metal based chemical adsorbent reacts with and / or adsorbs residual oxygen , hydrogen and carbon monoxide , thereby removing them from the conventional purity nitrogen gas stream and producing an ultra - high purity nitrogen gas stream . this ultra - high purity nitrogen gas stream exits the chemical adsorbent bed typically containing between 0 and 20 parts per billion each of hydrogen , carbon monoxide and oxygen , preferably containing between 0 and 10 parts per billion each of hydrogen , carbon monoxide and oxygen and most preferably containing between 0 and 1 part per billion each of hydrogen , carbon monoxide and oxygen . the gas purifier is designed to include at least one dual temperature sensor set 204 a and 204 b ; 205 a and 205 b ; 206 a and 206 b that is located in proximity to the chemical adsorbent 210 , as discussed above . these temperature sensors are relatively fragile and could break as the chemical adsorbent shifts during the transition from purification to regeneration and back . moreover , the temperature sensors need to be removed and replaced whenever they fail . as a result , the temperature sensors / detectors are inserted into the chemical adsorbent bed 210 through thermal wells , which project into the bed . the dual temperature sensors can be placed in one or several thermowells . the dual temperature sensors are used as part of a set so that temperature sensor failure can be detected while eliminating a false or misleading indication of a high chemical adsorbent temperature . the distinction between a temperature sensor failure and a high chemical adsorbent temperature is made by determining the temperature difference between the two temperature sensors in a given dual temperature sensor set . if both temperature sensors are functioning properly , this temperature difference should be small , since the temperature sensors in a given set ( for example , 204 a and 204 b ) are located in close proximity to one other . typically , the distance between the temperature sensors is between 0 and 6 inches , preferably between 0 and 3 inches and most preferably between 0 and 1 inch . however , if the difference in measured temperature between two temperature sensors in a given set ( for example , 204 a and 204 b ) exceeds a first predetermined value , typically between 5 ° f . and 100 ° f ., preferably between 10 ° f . and 40 ° f . and most preferably between 10 ° f . and 25 ° f ., one of the temperature sensors is determined to have failed and an alarm is initiated . a high chemical adsorbent temperature is not found to have occurred unless both temperature sensors in a given dual thermocouple set indicate a temperature that exceeds a second predetermined value . specifically , each temperature sensor in the dual temperature sensor set 204 a and 204 b ; 205 a and 205 b ; 206 a and 206 b generates an electric signal that is sent to a temperature sensor signal receiving computer card 207 a and 207 b . the temperature sensors associated with each dual temperature sensor set are wired to separate temperature sensor signal receiving computer cards . in this embodiment , temperature sensors 204 a , 205 a and 206 a are wired to temperature sensor signal receiving computer card 207 a and temperature sensors 204 b , 205 b and 206 b are wired to temperature sensor signal receiving computer card 207 b . in order to initiate a gas purifier shutdown , at least one temperature sensor must indicate a temperature that exceeds the second predetermined value on each temperature sensor signal receiving computer card . the second predetermined value is typically between 120 ° f . and 400 ° f ., preferably between 150 ° f . and 350 ° f . and most preferably between 150 ° f . and 300 ° f . the temperature sensor and temperature sensor signal receiving computer card logic is illustrated in fig3 . referring to this figure , the temperature difference between temperature sensors 204 a and 204 b is determined . if this difference exceeds the first predetermined value , one of the temperature sensors or the temperature sensor signal receiving computer card has failed and an alarm is sounded . in this situation the operator , would access the gas purifier and change out the malfunctioning equipment without having to take the purifier off - line . on the other hand , if the temperature difference does not exceed the first predetermined value , the temperature difference between sensors 205 a and 205 b is determined . if this difference exceeds the first predetermined value , one of the temperature sensors or the temperature sensor signal receiving computer card has failed and an alarm is sounded , and the procedure outlined above can be carried out . if this difference does not exceed the first predetermined value , the temperature difference between sensors 206 a and 206 b is determined . if the temperature difference exceeds the first predetermined value , one of the temperature sensors or the temperature sensor signal receiving computer card has failed and an alarm is sounded . if this difference does not exceed the first predetermined value , the actual value of the temperature readings is examined . if the temperature measured by at least one of the dual thermocouple in the dual set exceeds the second predetermined value , the chemical adsorbent temperature is too high and the gas purifier is isolated . the chemical adsorbent bed 210 is isolated by closing valves 220 , 230 and 240 . the chemical adsorbent bed may also be vented by opening valve 250 . if the temperature readings do not exceed the second predetermined value , the gas purifier is operating normally and no action is taken . the logic illustrated in fig3 is programmed into a computing device that contains the temperature sensor signal receiving computer cards . this device is typically a computer or programmable logic controller ( plc ). because at least one temperature sensor must indicate an excessive temperature on each temperature sensor signal receiving computer card to initiate a gas purifier shutdown , a single temperature sensor or temperature sensor signal receiving computer card failure will not cause the gas purifier to isolate . typically , the system is designed such that a single temperature sensor or temperature sensor signal receiving computer card failure will initiate an alarm to notify the operator that the failure has occurred . the chemical adsorbent requires periodic regeneration . referring again to fig2 , the regeneration nitrogen is heated in a heat exchanger 260 , typically to a temperature between 400 ° f . and 800 ° f ., preferably to a temperature between 400 ° f . and 700 ° f . and most preferably to a temperature between 400 ° f . and 600 ° f . the hot regeneration nitrogen stream is routed to the purifier 200 where it drives contaminants off of the chemical adsorbent 210 . generally , the contaminant - containing regeneration nitrogen is circulated counter to the direction in which the production gas is purified , and exits purifier 200 as waste . the temperature of the regeneration stream generally exceeds the temperature that initiates a chemical adsorbent bed shutdown . therefore , the chemical adsorbent bed high temperature shutdown is disregarded during regeneration . however , a single temperature sensor or temperature sensor signal receiving computer card failure can still be detected because these are identified based on temperature difference , not absolute temperature . while the invention has been described in detail with reference to specific embodiments thereof , it will become apparent to one skilled in the art that various changes and modifications can be make , and equivalents employed .	1
referring to the drawings in detail wherein like numerals designate like parts , a rectangular steel casing or shell 10 , which may be thermally insulated , is filled with fresh water or another thermal transfer liquid , such as glycol , to the approximate level 11 , fig2 . preferably , the shell 10 has attached skids 12 to protect the bottom wall of the unit from deck water on a ship , and to facilitate handling by a forklift truck . fixed within the shell 10 midway between its two side walls 13 is a rectangular firebox 14 which shares the bottom wall 15 of the shell 10 . as best shown in fig3 a vertical water - tight bulkhead 16 extends between the shell side walls 13 and defines the front of the fresh water chamber of the unit . the bulkhead 16 is spaced slightly forwardly of the front wall of the firebox 14 to form an intervening liquid - filled space . the rear wall 17 of the firebox is spaced forwardly of the rear parallel wall 18 of shell 10 . the top wall 19 of the firebox is at a level well above the bottom wall 15 . the firebox 14 is thus surrounded by liquid on all sides and at its top . only its bottom wall is a dry wall . there is no necessity for any refractory lining of the firebox due to its immersion in liquid , which prevents warping of its walls . the dry bottom wall 15 of the firebox promotes rapid ignition and more complete burning of oil or other fuel in the firebox . in this connection , the device may utilize liquid , gaseous or solid fuels , depending upon availability , convenience and the particular application of the heating unit . a relatively shallow adapter sleeve 20 rises from the top of the firebox 14 and is in open communication with its combustion chamber . on top of this adapter sleeve is fixedly mounted a primary heat exchanger assembly 21 consisting of a unitized group of open - ended vertical axis fire tubes 22 , preferably arranged in three spaced parallel transverse rows of six fire tubes each and six spaced front - to - back parallel rows of three tubes each , fig3 . different numbers of fire tubes in a different configuration and size may be employed in some cases . the open top and bottom ends of the fire tubes are united with horizontal flange plates 23 and 24 , as shown . the lower flange plate 24 is fixed to the adapter sleeve 20 , and the top flange plate 23 is similarly fixed to the bottom of a heat exchanger cap or hood 25 which leads upwardly to and communicates directly with an exhaust stack 26 for gaseous combustion products rising from the fire tubes 22 . the primary heat exchanger 21 including all of the fire tubes 22 and the cap 25 are submerged in the water or other liquid contained in the shell 10 and therefore are in direct heat transfer relationship with such liquid . the top wall of the shell 10 is preferably in the form of a detachable and removable plate 27 held in place by fastening means 28 , thereby allowing ready access at required times to the interior of the heating unit . a short sleeve extension 29 rises above the removable top wall 27 and is united therewith in spaced surrounding relationship to the exhaust stack 26 . the interior of the shell 10 is vented to atmosphere by a series of spaced splash plates 30 fixedly held within the sleeve 29 . in this connection , the liquid heating unit is completely unpressurized device , distinguishing it from a classic boiler which is a pressurized device . the splash plates 30 prevent the liquid contained in the shell 10 from splashing out of the top of the unit when a ship carrying it is in rough water , as with diver utilization of the invention . preferably , a rain cover 30 &# 39 ; is provided above the exhaust stack 26 , and a heat baffle , not shown , may be placed in the area between the stack 26 and forward fuel tanks . in connection with diver utilization , preferably a pair of secondary heat exchangers 31 in the form of finned copper tubing coils are supported in a submerged state in the liquid chambers at the opposite sides of firebox 14 and between the firebox and shell side walls . the secondary heat exchanger coils , as best shown in fig2 may extend vertically for the major portion of the height of the shell 10 . in the front - to - back direction , fig3 the secondary heat exchanger coils extend at least along the two opposite side walls of the firebox 14 and may extend rearwardly of the firebox , if desired . the secondary heat exchangers could , in some cases , be located at other locations within the shell 10 instead of the two side positions illustrated . in still other cases , only a single secondary heat exchanger may be utilized , or more than two secondary heat exchangers could be used , if desirable . in diver utilization of the invention , sea water is pumped through the secondary heat exchanger coils 31 and such water or other liquid is heated in direct proportion to the temperature maintained in the liquid filling the shell 10 by operation of the primary heat exchanger 21 . the thus heated liquid in the secondary heat exchanger coils 31 is then circulated through the suit of a diver or divers and then is discharged from the suit or suits back into the sea . any suitable pumping arrangement , not shown , such as a submersible pump or an on - board pump , may be used to maintain circulation of the sea water through the coils 31 in the described manner . when the unit is employed for non - diver applications , the secondary heat exchangers 31 can be shut off or omitted entirely . water or other suitable liquid in the shell 10 can be maintained at a proper level therein by conventional pumping means , not shown , and this liquid will be heated by the primary heat exchanger 21 and can be delivered in a closed loop system or systems to remote heat exchangers , such as radiators for heating a building or for other like purposes . thus , the invention is versatile in its use capabilities as well as being simplified , substantially self - contained and efficient and economical in operation . at the front of the rectangular unit , forwardly of the bulkhead 16 , upper and lower dry service compartments 32 and 33 , fig1 are provided . within the upper compartment 16 is an electrical control panel 34 for instrumentation including aquastat temperature controls and temperature gages , not shown . also , in the compartment 16 , are sea water strainers 35 through which incoming sea water must pass before being delivered to the secondary heat exchanger coils 31 as shown schematically in fig4 . the sea water heated within the coils 31 is delivered to a manifold 36 in the compartment 16 having several different delivery lines 37 through which warm water can be delivered to one or more divers through hoses of sufficient lengths . as previously , stated , the water after passing through the diver &# 39 ; s suit is expelled back into the sea . in the lower front compartment 33 , twin oil or gas burner gun units 38 are fixed to mounting flanges 39 on the forward ends of short gun spacer pipes 39 &# 39 ; which are attached to the forward vertical wall of the firebox 14 , fig3 . the use of the spacer pipes 39 &# 39 ; for mounting the fuel guns 38 prevents overheating of the fuel guns , as might occur if they were in direct thermal contact with the firebox . the narrow water space at the front of the firebox adjacent to the bulkhead 16 also keeps the temperature of the guns 38 within a safe range . the guns 38 , which are conventional , deliver oil or other fuel directly into the combustion chamber defined by the firebox 14 where the fuel is ignited and burned . on opposite sides of the two front compartments 32 and 33 , built - in vertically elongated fuel storage tanks 40 extend from the top to the bottom of the shell 10 . a connecting upper horizontal tank 40 &# 39 ; extends between and communicates with the two vertical tanks 40 for added fuel storage capacity . double folding doors 41 are provided to cover the compartments 32 and 33 , and when opened these doors can fold flat against the fronts of tanks 40 . a single rear dry service compartment 42 having hinged doors 43 is recessed into the rear of the shell 10 and thus projects into the rear water chamber of the shell behind the firebox 14 . within opposite sides of the service compartment 42 can be installed forwardly projecting dual back - up electrical heating elements 44 for the diver application of the invention . these back - up heating elements assure sufficient heating of the fresh water or other liquid in the shell 10 for life support even in the event of complete failure of the primary heat exchanger 21 due to combustion failure in the firebox 14 . in lieu of the electrical back - up elements 44 , steam heated dual back - up elements , not shown , can be employed in some cases . it is also possible to provide a back - up emergency heating element , either steam or electric , across the rear liquid chamber of the shell 10 beneath the compartment 42 or at other locations in the shell . an electrical control panel 45 for electric heat sensors , not shown , aquastat temperature gages , etc . are provided in the rear service compartment 42 . inasmuch as warmth is vital to the survival of divers , it may be seen that in addition to providing one or more back - up heating means within the shell 10 the invention throughout provides dual or redundant prime operating components including the dual burner guns 38 , dual secondary heat exchangers 31 , and dual back - up heating elements 44 . the maximum safety of the diver relying on the heating system is thus assured . when using solid fuel , the fuel gun mounting flanges 39 can be easily adapted to a solid fuel auger for automated feed , or replaced with a door arrangement to provide solid fuel and combustion air access to the firebox 14 . it is to be understood that the form of the invention herewith shown and described is to be taken as a preferred example of the same , and that various changes in the shape , size and arrangement of parts may be resorted to , without departing from the spirit of the invention or scope of the subjoined claims .	1
now , embodiments of the present invention will be described in detail with reference to the accompanying drawings . configurations of the present invention for performing encoding and decoding using panning ( hereinafter “ balance adjustment ”) will be explained using the following configuration . that is to say , using part of the configuration of an encoder ( that is , the configuration removing the part for generating side signals from the left half configuration shown in fig . b . 13 ) used widely as an aac ( advanced audio codec ), which is a standard mpeg - 2 and mpeg - 4 system in iso / iec given in “ iso / iec 14496 - 3 : 1999 ( e ) “ mpeg - 2 ”, p . 232 , fig . b . 13 ″ ( hereinafter “ non - patent literature 3 ), by adding intensity stereo components disclosed in patent literature 1 to the right half of this configuration and adding encoders to the respective output destinations of individual signals , an overall configuration for encoding and transmitting all information is given . furthermore , a stereo signal is designed so that , by receiving different audio signals in the left ear and the right ear , a listener can enjoy audio with realistic sensation . consequently , with audio sigils to provide content , the simplest stereo signal is a two - channel signal comprised of an l signal and an r signal , and a case where an input signal is a two - channel signal will be described with the present embodiment . first , the configuration of an encoding apparatus according to am embodiment of the present invention will be described . fig1 is a block diagram showing a configuration of encoding apparatus 100 according to the present embodiment . fig1 shows a configuration to perform scalable ( multilayer - structure ) coding of stereo signals , that is , to encode an m signal in a core encoder and then encode a stereo signal in the frequency domain using a decoded signal generated by decoding in a core decoder . encoding apparatus 100 is formed primarily with down mixing section 101 , core encoder 102 , core decoder 103 , modified discrete cosine transform ( hereinafter referred to as “ mdct ( modified discrete cosine transform )”) section 104 , mdct section 105 , mdct section 106 , down mixing section 107 , adding section 108 , quantizing apparatus 109 , multiplying section 110 , multiplying section 111 , adding section 112 , adding section 113 , encoder 114 , encoder 115 and encoder 116 . down mixing section 101 receives as input an l signal ( first signal ) and an r signal ( second signal ), which are vectors of a predetermined length , and provides an m signal ( third signal ) by down - mixing the l signal and r signal received as input . down mixing section 101 also outputs the m signal found , to core encoder 102 . equation 1 is an example of a down mixing calculation method in down mixing section 101 . the present embodiment uses a most simple down mixing method of adding an l signal and an r signal and multiplying the result by 0 . 5 . core encoder 102 finds a code by encoding the m signal received as input from down mixing section 101 , and outputs the found code to core decoder 103 and multiplexing section 117 . core decoder 103 generates a decoded signal by decoding the code received as input from core encoder 102 , and outputs the generated decoded signal to mdct section 105 . mdct section 104 receives as input the l signal , performs a discrete cosine transform of the l signal received as input , and transforms the time domain signal to a frequency domain signal ( frequency spectrum ). mdct section 104 outputs the transformed signal to down mixing section 107 , adding section 112 and quantizing apparatus 109 . mdct section 105 performs a discrete cosine transform of the decoded signal received as input from core decoder 103 , and transforms the time domain signal into a frequency domain signal ( frequency spectrum ). mdct section 105 outputs the transformed signal to adding section 108 . mdct section 106 receives as input an r signal , performs a discrete cosine transform of the r signal received as input , and transforms the time domain signal into a frequency domain signal ( frequency spectrum ). mdct section 106 outputs the transformed signal to down mixing section 107 , adding section 113 and quantizing apparatus 109 . down mixing section 107 finds an m signal by down mixing the l signal received as input from mdct section 104 and the r signal received as input from mdct section 106 . down mixing section 107 outputs the found m signal to adding section 108 . down mixing section 107 is different from down mixing section 101 in down mixing a frequency domain signal , not a time domain signal . the down mixing calculation method is the same as equation 1 and will not be described here . adding section 108 subtracts the signal received as input from mdct section 105 , from the m signal received as input from down mixing section 107 , and calculates an m signal of the target ( hereinafter referred to as “ target m signal ”). then , adding section 108 outputs the calculated target m signal to multiplying section 110 , multiplying section 111 , encoder 115 and quantizing apparatus 109 . quantizing apparatus 109 encodes a balancing weight coefficient to use for balance adjustment and finds a weight coefficient code , using the l signal received as input from mdct section 104 , the target m signal received as input from adding section 108 , and the r signal received as input from mdct section 106 . then , quantizing apparatus 109 outputs the found code to multiplexing section 117 . quantizing apparatus 109 acquires balancing weight coefficient w l , ( hereinafter referred to as “ l signal balancing weight coefficient w l ”) to adjust the amplitude balance of the target m signal with respect to the l signal by decoding found code , and sets acquired l signal balancing weight coefficient w l in multiplying section 110 . quantizing apparatus 109 acquires balancing weight coefficient w r ( hereinafter referred to as “ r signal balancing weight coefficient w r ”) to adjust the amplitude balance of the target m signal with respect to the r signal , using acquired l signal balancing weight coefficient w l , and sets acquired r signal balancing weight coefficient w r in multiplying section 111 . the configuration of quantizing apparatus 109 will be described in detail later . multiplying section 110 multiples the target m signal received as input from adding section 108 , by l signal balancing weight coefficient w l received as input from quantizing apparatus 109 , and outputs the result to adding section 112 . multiplying section 111 multiplies the target m signal received as input from adding section 108 , by r signal balancing weight coefficient w r received as input from quantizing apparatus 109 , and outputs the result to adding section 113 . adding section 112 subtracts the target m signal multiplied by l signal balancing weight coefficient w l , received as input from multiplying section 110 , from the l signal received as input from mdct section 104 , and finds an l signal of the target ( hereinafter “ target l signal ”). adding section 112 outputs the found target l signal to encoder 114 . adding section 113 subtracts the target m signal multiplied by r signal balancing weight coefficient w r , received as input from multiplying section 111 , from the r signal received as input from mdct section 106 , and finds an r signal of the target ( hereinafter “ target r signal ”). adding section 113 outputs the found target r signal to encoder 116 . the calculations in adding section 112 and adding section 113 can be represented by equations 2 . { circumflex over ( r )} f = r f − w r ·{ circumflex over ( m )} f ( equations 2 ) the above algorithms are equivalent to transformation of an l signal and an r signal using balance adjustment . the balancing weight coefficients show the similarity between the target m signal and the l and r signals . consequently , a target l signal and a target r signal , given by subtracting the target m signal multiplied by balancing weight coefficients from an l signal and an r signal , become signals in which redundant parts are removed by the target m signal and in which signal power is reduced , so that the target l signal and target r signal both can be encoded efficiently . encoder 114 outputs a code found by encoding the target l signal received as input from adding section 112 , to multiplexing section 117 . encoder 115 outputs a code found by encoding the target m signal received as input from adding section 108 , to multiplexing section 117 . encoder 116 outputs a code found by encoding the target r signal received as input from adding section 113 , to multiplexing section 117 . multiplexing section 117 multiplexes the codes received as input from core encoder 102 , quantizing apparatus 109 , encoder 114 , encoder 115 and encoder 116 , and outputs a multiplexed bit stream . next , the configuration of quantizing apparatus 109 will be described using fig2 . fig2 is a block diagram showing a configuration of quantizing apparatus 109 . quantizing apparatus 109 is formed primarily with power / correlation calculating section 201 , intermediate value calculating section 202 , codebook 203 , search section 204 and decoding section 205 . power / correlation calculating section 201 performs power calculation and correlation value calculation using the l signal received as input from mdct section 104 , the target m signal received as input from adding section 108 , and the r signal received as input from mdct section 106 . then , power / correlation calculating section 201 outputs the calculated power and correlation value , to intermediate value calculating section 202 . the power and correlation value can be found by equations 3 . c { circumflex over ( m )}{ circumflex over ( m )} : power of target m signal c { circumflex over ( m )} l : correlation value between target m signal and l signal c { circumflex over ( m )} r : correlation value between target m signal and r signal intermediate value calculating section 202 finds two intermediate values using the power and correlation value received as input from power / correlation calculating section 201 . then , intermediate value calculating section 202 outputs the found intermediate values to search section 204 . for example , intermediate value can be determined using equations 4 . a 2 =− 2 . 0 · c { circumflex over ( m )} l − 4 . 0 · c { circumflex over ( m )} m + 2 . 0 . · c { circumflex over ( m )} r ( equations 4 ) codebook 203 is information that is stored in a memory means such as a rom ( read only memory ), and is formed with a plurality of scalar values to be selected as an l signal weight coefficient . fig3 shows , by way of example , scalar values numbered and stored in codebook 203 of the present embodiment . the scalar values stored in codebook 203 are only the l values of balancing weight coefficients . search section 204 searches for an optimal one of a plurality of scalar values stored in codebook 203 , and encodes a balancing weight coefficient by selecting a number corresponding to the optimal scalar value found . to be more specific , for example , search section 204 searches for number n to minimize the cost function shown in equation 5 . search section 204 outputs selected number n to multiplexing section 117 as a code . search section 204 outputs the code having been outputted to multiplexing section 117 , to decoding section 205 . a 1 ·( w l n ) 2 + a 2 · w l n ( equation 5 ) w l n : scalar value of number n stored in codebook 203 referring to equation 5 , although scalar values stored in codebook 203 are squared , in this case , search is made possible by even a smaller amount of calculation by storing square values in codebook 203 in advance . decoding section 205 finds an l signal balancing weight coefficient by decoding a code ( number n ) received as input from search section 204 ( w l = w l n ). that is to say , decoding section 205 picks up a scalar value corresponding to the code ( number n ) received as input from search section 204 , out of a plurality of scalar values stored in codebook 203 , as an l signal balancing weight coefficient . decoding section 205 uses the result of subtracting the acquired l signal balancing weight coefficient from a predetermined constant , as an r signal balancing weight coefficient . for example , decoding section 205 finds an r signal balancing weight coefficient ( w r = 2 . 0 − w l n ) by subtracting the l signal balancing weight coefficient from the constant 2 . 0 . here n is an l signal balancing weight coefficient code , and w l and w r are decoded balancing weight coefficients . the constant 2 . 0 is a value set according to the quantitative relationships between signals upon down mixing in down mixing section 101 . the reason to find an r signal balancing weight coefficient by subtracting an l signal balancing weight coefficient from the constant 2 . 0 , will be described later . decoding section 205 sets the l signal balancing weight coefficient in multiplying section 110 and sets the r signal balancing weight coefficient in multiplying section 111 . next , a detailed explanation will be given about the theoretical background of balance adjustment by means of quantized and decoded balancing weight coefficients according to the present invention . first , efficient coding of an l signal and r signal using balance adjustment is made possible by minimizing the power of the transformed values in equations 6 . the m signal in this case is an average value of an l signal and an r signal . where l ′ f and r ′ f in equation 6 are the same as shown in equation 7 next , calculating a balancing weight coefficient to minimize the l signal power in equations 6 gives equation 8 . similarly , in equations 6 , the balancing weight coefficient to minimize the power in the equation for the r signal is shown as equation 9 . that is to say , l signal power and r signal power can be minimized by selecting the balancing weight coefficients of equations 8 and 9 above . furthermore , given that the m signal holds the relationship of equation 1 , the addition result of an l signal balancing weight coefficient and an r signal balancing weight coefficient can be represented by equation 10 , from equation 1 and equations 3 . although with the present embodiment a target m signal is quantized in a scalable fashion as shown in fig1 , not based on the simple relationship of equation 1 , but , presuming that the relationship of equation 1 is predominant , balancing weight coefficients are quantized based on the relationship of equation 10 . based on this presumption , it is possible to quantize ( encode ) only one parameter , allowing low bit rate coding . furthermore , it is also possible to quantize l signal balancing weight coefficient w l alone using codebook 203 , and find r signal balancing weight coefficient w r from the relationship of equation 10 . cost function f of search in this case can be represented by equation 11 . in above equation 11 , the third term is not related to l signal balancing weight coefficient w l and therefore omitted , and only the sum of the first term and the second term is used as a cost function . the values multiplied upon the balancing weight coefficients are the two intermediate values shown in equations 4 . furthermore , when this cost function is smaller , the total sum of a target l signal and a target r signal can be made smaller , and searching for such l signal balancing weight coefficient w l is equivalent to quantizing ( encoding ) an optimal balancing weight coefficient . by using balancing weight coefficients found by means of the above coding , it is possible to reduce target l signal power and target r signal power and consequently transmit sound / speech of good quality at low bit rates . a verification test of the present embodiment has been conducted and its result will be explained next . the encoder that was used was a codec simulator to perform the same scalable spectrum quantization of stereo signals ( 16 khz sampling ) as in non - patent literature 3 . the evaluation data was data ( 24 seconds ) appending six sounds / voices given from varying source positions . the number of balancing weight coefficient quantization bits was four . the result of performing a verification test based on the above conditions was that , by replacing a conventional encoding apparatus with the encoding apparatus of the present embodiment , the amount of calculation when finding balancing weight coefficients according to the present embodiment and performing quantization was 3 / 5 compared to heretofore . consequently , with the present embodiment , the amount of calculation was saved significantly compared to heretofore . reasons this significant effect could be achieved may include that a calculation to involve a complex arithmetic operation and increase the amount of calculation , such as division , is not performed , and that the number of pairs of numbers and scalar values stored in codebook 203 is comparatively small , that is , sixteen variations , so that these can be specified by only dour bits . thus , with the present invention , balancing weight coefficients themselves are not calculated , so that the amount of calculation is reduced and more efficient quantization is made possible . a feature of the present embodiment lies in performing different calculations from embodiment 1 in a quantizing apparatus upon performing coding and decoding using balance adjustment . with the present embodiment , the encoding apparatus configuration is the same as in fig1 and explanations will be omitted . also , with the present embodiment , the quantizing apparatus configuration is the same as in fig2 . in the following description , codes in fig1 and fig2 will be used . power / correlation calculating section 201 performs power calculation and correlation value calculation using the l signal received as input from mdct section 104 , the target m signal received as input from adding section 108 , and the r signal received as input from mdct section 106 . power / correlation calculating section 201 outputs the calculated power and correlation value to intermediate value calculating section 202 . power / correlation calculating section 201 finds power and correlation value by equations 12 . c1 { circumflex over ( m )}{ circumflex over ( m )} : adjusted power of target m signal c1 { circumflex over ( m )} l : adjusted correlation value of target m signal and l signal c1 { circumflex over ( m )} r : adjusted correlation value of target m signal and r signal in equations 12 , γ , η , and ζ , representing the proportions of power components to be added , may be variables or constants , or may be all different values . for example , experiment has shown that , when making γ , η , and ζ constants , good performance can be achieved by setting these three γ , η , and ζ to 0 . 25 . the adjusted power of a target m signal , the adjusted correlation value of a target m signal and an l signal , and the adjusted correlation value of a target m signal and an r signal , are provided by adjusting the power of a target m signal , the correlation value of a target m signal and an l signal , and the correlation value of a target m signal and an r signal using the power of an l signal , the power of an r signal , the sum of l signal power and r signal power , and the proportions of power components to be added ( three coefficients ). in the following description , the adjusted power of a target m signal will be redefined as the power of a target m signal , the adjusted correlation value of a target m signal and an l signal will be redefined as the correlation value between a target m signal and an l signal , and the adjusted correlation value of a target m signal and an r signal will be redefined as the correlation value of a target m signal and an r signal . when γ , η and ζ are made variables , power / correlation calculating section 201 performs equalization in order to reduce the variations of the variables over time . power / correlation calculating section 201 performs equalization by performing the calculation of equations 13 , applying the result to equations 14 , and updating each state . c 2 { circumflex over ( m )} r = α · c { circumflex over ( m )} r +( 1 − α )· s { circumflex over ( m )} r ( equations 13 ) c2 { circumflex over ( m )}{ circumflex over ( m )} : equalized power of target m signal c2 { circumflex over ( m )} l : equalized correlation value between target m signal and l signal c2 { circumflex over ( m )} r : equalized correlation value between target m signal and r signal s { circumflex over ( m )}{ circumflex over ( m )} : power state of target m signal s { circumflex over ( m )} l : correlation value state between target m signal and l signal s { circumflex over ( m )} r : correlation value state between target m signal and r signal c2 { circumflex over ( m )}{ circumflex over ( m )} : equalized power of target m signal c2 { circumflex over ( m )} l : equalized correlation value between target m signal and l signal c2 { circumflex over ( m )} r : equalized correlation value between target m signal and r signal s { circumflex over ( m )}{ circumflex over ( m )} : power state of target m signal s { circumflex over ( m )} l : correlation value state between target m signal and l signal s { circumflex over ( m )} r : correlation value between target m signal and r signal the three states in equations 13 and equations 14 , namely the power state of a target m signal , the correlation state of a target m signal and an l signal , and the correlation state of a target m signal and an r signal , are all variables to be stored in a static memory area during coding processing . consequently , upon starting coding processing , the three states need to be initialized to 0 . furthermore , α , which represents the proportion in equalization , may be either a variable or a constant . for example , experiment has shown that good performance can be achieved when α is set between 0 . 5 and 0 . 7 . when α is 1 . 0 , power / correlation calculating section 201 performs equalization . the equalized power of a target m signal , the equalized correlation value of a target m signal and an l signal , and the equalized correlation value of a target m signal and an r signal , are provided by equalizing the power of a target m signal , the correlation value of a target m signal and an l signal , and the correlation value of a target m signal and an r signal , using the power state of a target m signal , the correlation value state of a target m signal and an l signal , the correlation value state of a target m signal and an r signal and the proportions of equalization . in the following descriptions , the equalized power of a target m signal will be redefined as the power of a target m signal , the equalized correlation value of a target m signal and an l signal will be redefined as a correlation value of a target m signal and an l signal , and the equalized correlation value of a target signal and an r signal will be redefined as the correlation value of a target m signal and an r signal . with the present embodiment , the processings in intermediate value calculating section 202 , codebook 203 , search section 204 and decoding section 205 are the same as in embodiment 1 , and so their explanations will be omitted . the present embodiment is different from embodiment 1 in adding l signal power or r signal power in equations 12 . an effect of adding l signal power or r signal power will be explained below . first , the cost function is as shown in equation 11 . ω l to minimize this cost function is as shown in equation 15 , given that the result of partial differentiation is 0 . in equation 15 , when cross term c lr shows stable positive correlation ( that is , has a positive value ), ω l is a stable weight and gives little perceptual awkwardness . on the other hand , when cross term c lr shows negative correlation or moves wildly between positive and negative over time , although cost function f is made smaller , decoded sound / speech obtained in a decoder using that weight is perceptually awkward sound / speech in which sound pressure moves to the left and the right wildly . this is a specific phenomenon seen when there is significant coding distortion . then , in quantization of weight , if the cost function is modified in a direction to be less influenced by the value of cross term c lr , it is possible to achieve good sound / speech quality even when there is significant coding distortion . if each term in equations 4 is developed top be in proximity with a signal given by down mixing a target m signal , the result can be represented by equations 16 . a 1 = 2 . 0 · c { circumflex over ( m )}{ circumflex over ( m )} ≅ 0 . 5 ·( c llrr + 2 . 0 · c lr ) a 2 =− 2 . 0 · c { circumflex over ( m )} l − 4 . 0 · c { circumflex over ( m )} m + 2 . 0 · c { circumflex over ( m )} ≅( c ll + c lr )−( c llrr + 2 . 0 · c lr )+( c rr + c lr ) ( equations 16 ) to reduce the influence of cross term c lr included in each term of equations 16 , the values of the terms of power besides cross term c lr may be added and increased . this is a significant element of the present embodiment . consequently , in the end , equations 12 can be derived . experiment has verified that good sound / speech quality can be achieved when the transmission rate is low ( that is , when there is significant coding distortion ). in equations 12 , addition of the values of the terms of power besides cross term c lr is addition of known signal power , so that the amount of calculation required for weight quantization does not increase significantly . consequently , a significant effect can be achieved at a small increase in the amount of calculation . according to the present embodiment , in addition to the advantages of above embodiment 1 , by reducing the influence of cross term between a plurality of signals , it is possible to achieve good sound / speech quality by preventing awkward sound / speech quality in which , for example , sound pressure varies significantly , prevent the amount of calculation from increasing , and achieve good sound / speech quality . a feature of the present embodiment lies in performing different calculations from those of embodiment 1 and embodiment 2 , in a quantizing apparatus , upon performing coding and decoding using balance adjustment . the encoding apparatus configuration of the present embodiment is the same as in fig1 , and its explanations will be omitted . with the present embodiment , the quantizing apparatus configuration is the same as in fig2 . in the following description of a quantizing apparatus , codes in fig1 and fig2 will be used . power / correlation calculating section 201 performs power calculation and correlation value calculation using the l signal received as input from mdct section 104 , the target m signal received as input from adding section 108 , and the r signal received as input from mdct section 106 . power / correlation calculating section 201 outputs the calculated power and correlation value , to intermediate value calculating section 202 . power / correlation calculating section 201 finds the power and correlation value using equations 12 and equations 17 . equations 17 provides an algorithm to support embodiment 1 and equations 12 provides an algorithm to support embodiment 2 . c { circumflex over ( m )}{ circumflex over ( m )} : power of target m signal c { circumflex over ( m )} l : correlation value between target m signal and l signal c { circumflex over ( m )} r : correlation value between target m signal and r signal when power and correlation value are found using equations 12 , power / correlation calculating section 201 performs equalization as represented by equations 13 and equations 14 in order to reduce the variations of variables in equations 12 over time . when power and correlation value are found using equations 17 , power / correlation calculating section 201 performs equalization by performing the calculation of equations 18 , applying the result of equations 18 to equations 19 and updating each state . c3 { circumflex over ( m )}{ circumflex over ( m )} : equalized power of target m signal c3 { circumflex over ( m )} l : equalized correlation value between target m sign al and l signal c3 { circumflex over ( m )} r : equalized correlation value between target m sign al and r signal s { circumflex over ( m )}{ circumflex over ( m )} : equalized power of target m signal s { circumflex over ( m )} l : correlation value state between target m signal an d l signal s { circumflex over ( m )} r : correlation value state between target m signal an d r signal c3 { circumflex over ( m )}{ circumflex over ( m )} : equalized power of target m signal c3 { circumflex over ( m )} l : equalized correlation value of target m signal and l signal c3 { circumflex over ( m )} r : equalized correlation value of target m signal and r signal s { circumflex over ( m )}{ circumflex over ( m )} : power state of target m signal s { circumflex over ( m )} l : correlate values state between target m signal an d l signal s { circumflex over ( m )} r : correlation value state between target m signal an d r signal the equalized power of a target m signal , the equalized correlation value of a target m signal and an l signal , and the equalized correlation value of a target m signal and an r signal , are provided by equalizing the power of a target m signal , the correlation value of a target m signal and an l signal , and the correlation value of a target m signal and an r signal , using the power state of a target m signal , the correlation value state of a target m signal and an l signal , the correlation value state of a target m signal and an r signal and the proportions of equalization . in the following descriptions , the equalized power of a target m signal will be redefined as the power of a target m signal , the equalized correlation value of a target m signal and an l signal will be redefined as a correlation value of a target m signal and an l signal , the equalized correlation value of a target signal and an r signal will be redefined as the correlation value of a target m signal and an r signal , the equalized power of an l signal will be redefined as the power of an l signal , and the equalized power of an r signal will be redefined as the power of an r signal . intermediate value calculating section 202 finds five intermediate values using the power and correlation value received as input from power / correlation calculating section 201 . intermediate value calculating section 202 outputs the found intermediate values to search section 204 . for example , intermediate values can be found using equations 20 . α 2 =− 4 . 0 · c { circumflex over ( m )}{ circumflex over ( m )} + 2 . 0 · c { circumflex over ( m )} r α 4 = 4 . 0 · c { circumflex over ( m )}{ circumflex over ( m )} − 4 . 0 · c { circumflex over ( m )} r + c rr ( equations 20 ) where α 0 , α 1 , α 2 , α 3 , α 4 : intermediate values codebook 203 is information that is stored in a memory means such as a rom and is formed with a plurality of scalar values to be selected as an l signal balancing weight coefficient , weight coefficients , and calculated value found from weigh coefficients . the content of information to be stored in codebook 203 will be described later . search section 204 searches for an optimal one of a plurality of scalar values stored in codebook 203 , and encodes a balancing weight coefficient by selecting a number corresponding to the optimal scalar value found . to be more specific , for example , search section 204 searches for number n to minimize the cost function shown in equation 21 . search section 204 outputs selected number n to multiplexing section 117 as a code . search section 204 outputs the code having been outputted to multiplexing section 117 , to decoding section 205 . the processing in decoding section 205 according to the present embodiment is the same as in above embodiment 1 and so will not be described . α 0 · w 0 n + α 1 · w 1 n α 2 · w 2 n + α 3 · ω l n + α4 · ω r n ( equation 21 ) where ω l n , ω r n : scalar values of number n stored in codebook 203 ( weight coefficients for l signal and r signal ) w 0 n , w 1 n , w 2 n : values determined using scalar value of nu mber n stored in codebook 203 ( balancing weight coefficient f or l signal ) and weight coefficients for l signal and r signal n : number ( number n to minimize cost function beco mes code ) this concludes the explanation of the configuration of quantizing apparatus 109 . the idea of the present embodiment and the method of designing codebook 203 of the present embodiment will be explained next . although the theoretical background of balance adjustment is the same as described with embodiment 1 , the cost function of the present embodiment is different from those of embodiment 1 and embodiment 2 . although embodiment 1 and embodiment 2 use the cost function of equation 11 , when the cost function of equation 11 is used , good sound / speech quality can be achieved when there is not much difference between the power of signal l f and the power of signal r f , but , when there is a significant difference between the power of signal l f and the power of signal r f ( that is , when balancing weight coefficient w n l is extremely small or when balancing weight coefficient w n l is extremely large ), the one of the l signal side and the r signal side having the greater power becomes predominant , and the one of the smaller power becomes not worth evaluating . in that case , a phenomenon occurs where the signal of the one of the smaller power becomes even smaller . in embodiment 1 and embodiment 2 , the distortion of the signal of the smaller power becomes smaller , so that the sound / speech quality of the predominant signal improves and good sound / speech quality can be achieved . there is also a method to keep the power of a signal of a small sound that is heard with a big sound from falling , and , in that case , ingenuity would be required . so , the present embodiment uses the cost function of equation 22 below . where ω l , ω r : weight coefficients for l signal and r signal that is to say , the difference between l signal power and r signal power can be learned from the scale of the reconstructed l signal balancing weight coefficient , so that the above technical problems can be solved by performing weighting of the corresponding cost function . the present embodiment uses the weight coefficients shown in fig4 . fig4 shows part of information stored in codebook 203 of the present embodiment . in fig4 , the size of codebook 203 is 16 ( four bits ). as obvious from fig4 , when the value of l signal weight coefficient ω l is small , the value of r signal weight coefficient ω r is set large , and , when the value of r signal weight coefficient ω r is small , the value of l signal weight coefficient ω l is set large . by this means , the weight of the cost function of equation 22 can be adjusted . now , the intermediate values are found by developing the cost function of equation 22 . the developed equations are shown as equation 23 . in equation 21 , calculated values w n 0 , w n 1 , and w n 2 , necessary for the calculation of equation 21 , are found in advance by equations 24 below , and stored in codebook 203 . thus , according to the present embodiment , it is possible to find intermediate values by equation 20 , find scalar values efficiently following the above steps using codebook 203 and equation 21 , and quantize balancing weight coefficients . as a result of this , even when there is a significant difference between the values of the two terms of the l signal side and the r signal side constituting the cost function , the deterioration of the signal of the smaller value , caused by the fact that the term of the greater value becomes predominant , can be prevented , and , consequently , synthesized speech of good overall sound / speech quality can be acquired . although with the present embodiment the size of the codebook is sixteen variations ( four bits ), the present invention is by no means limited to this , and other sizes can obviously be used as well , because the present invention does not rely upon the size of the codebook . although examples have been given with above embodiments 1 through embodiment 3 where coding is performed in a scalable configuration in which an m signal is encoded in core encoder 102 before a stereo signal is quantized , the present invention is by no means limited to this and is equally applicable to stereo signal coding without a core encoder . this is because the present invention is designed to encode a balancing weight coefficient efficiently taking advantage of the fact that an m signal is produced by down mixing , and because the present invention therefore does not rely upon the presence or absence of a core encoder . regarding the m signal to be processed in quantizing apparatus 109 , although the difference between an m signal acquired by down mixing and a decoded signal obtained by core decoder 103 is used as a target m signal , the present invention is not limited to this , and it is equally possible to process a decoded signal or an m signal subjected to down mixing , in quantizing apparatus 109 . this is because the present invention is designed to encode a balancing weight coefficient efficiently taking advantage of the fact that an m signal is produced by down mixing , and because the present invention therefore does not rely upon the quality of an m signal . although embodiment 1 to embodiment 3 above disclose cases where the sum of the balancing weight coefficients of an l signal and an r signal is 2 . 0 , the present invention is by no means limited to this , and the sum of the balancing weight coefficients of an l signal and an r signal may be values other than 2 . 0 , such as 1 . 9 , 1 . 85 , etc ., given that the optimal value might vary depending on the nature of an m signal . a possible interpretation of the present embodiment is that some of the characteristics of an m signal are lost , due to down minimizing , from a target m signal obtained in core encoder 102 , so that there is a possibility to achieve good coding performance by setting values slightly lower than 2 . 0 . to be more specific , a possible method is to , for example , evaluate coding performance by changing this sum value little by little and using this sum value as the value of the sum of the balancing weight coefficients of an l signal and an r signal for encoding , on a fixed basis . although with embodiment 1 to embodiment 3 above down mixing is performed after transformation into the frequency domain , the present invention is by no means limited to this , and the present invention obviously maintains valid even if a signal having been down mixed in the time domain is transformed into the frequency domain , because the present invention does not rely upon in which domain down mixing is performed . although in embodiment 1 through embodiment 3 above the mdct is used as the method of transformation into the frequency domain , the present invention is by no means limited to this , and it is equally possible to use any digital transformation method resembling the mdct such as the dct and fft , because the present invention does not rely upon the method of frequency domain transformation . although the three signals in embodiments 1 to embodiment 3 above were time domain signals , it is equally possible to use frequency domain signals or segments of these signals , because the present invention does not rely upon the nature of vectors . codes acquired in embodiment 1 to embodiment 3 above may be transmitted when used for communication or may be stored in a recoding medium ( such as a memory , disc or print code ) when used for storage , because the present invention does not rely upon the usage of codes . although cases with two channels have been described above with embodiments 1 to embodiment 3 , the present invention is by no means limited to this and is equally applicable to cases of multiple channels ( e . g . 5 . 1 ch ). although with embodiment 1 to embodiment 3 above an l signal , r signal and m signal are subject to coding , the present invention is by no means limited to this , and it is equally possible to encode frequency spectrums of an l signal , r signal , and m signal , or segments of these , as a first signal , second signal and third signal . although with embodiment 1 to embodiment 3 above balance adjustment for a target m signal is performed prior to encoding , the present invention is by no means limited to this , and it is equally possible to perform encoding prior to balance adjustment . that is to say , encoder 115 may be placed in a location closer to input than adding section 108 , because the present invention does not rely upon whether balance adjustment is performed before or after encoding . although the above descriptions have shown preferred embodiments of the present invention by way of example , this by no means limits the scope of the present invention . the present invention is applicable to any system featuring a coding apparatus . the quantizing apparatus and encoding apparatus according to the present invention can be provided in a communication terminal apparatus and base station apparatus in a mobile communication system , so that it is possible to provide a communication terminal apparatus , base station apparatus and a mobile communication system having the same operations and effects . also , although cases have been described with the above embodiment as examples where the present invention is configured by hardware , the present invention can also be realized by software . for example , it is possible to write the algorithms of the present invention in a programming language , store this program in a memory , and , by running this program using an information processing means , implement the same functions as those of the coding apparatus of the present invention . each function block employed in the description of each of the aforementioned embodiments may typically be implemented as an lsi constituted by an integrated circuit . these may be individual chips or partially or totally contained on a single chip . “ lsi ” is adopted here but this may also be referred to as “ ic ,” “ system lsi ,” “ super lsi ,” or “ ultra lsi ,” depending on differing extents of integration . further , the method of circuit integration is not limited to lsi &# 39 ; s , and implementation using dedicated circuitry or general purpose processors is also possible . after lsi manufacture , utilization of a programmable fpga ( field programmable gate array ) or a reconfigurable processor where connections and settings of circuit cells within an lsi can be reconfigured is also possible . further , if integrated circuit technology comes out to replace lsi &# 39 ; s as a result of the advancement of semiconductor technology or a derivative other technology , it is naturally also possible to carry out function block integration using this technology . application of biotechnology is also possible . the disclosure of japanese patent application no . 2008 - 205643 , filed aug . 8 , 2008 , japanese patent application no . 2009 - 59502 , filed mar . 12 , 2009 , and japanese patent application no . 2009 - 95260 , filed apr . 9 , 2009 , including the specifications , drawings and abstracts , are incorporated herein by reference in their entirety . the quantizing apparatus , encoding apparatus , quantizing method and encoding method of the present invention are suitable for use to , for example , encode a stereo audio signal at a low bit rate .	6
with reference now to fig1 . compost is formed by grinding organic waste comprising bagged cuttings , clippings and unsalable produce to a reduced size , preferably of a size that will pass through a screen having a hole size of 6 inches square ( 6 &# 34 ;× 6 &# 34 ;) or more . any plastic containers ( bags ) for the green waste is ground with the green waste and remains with it until separated in accordance with the invention . the green waste is stored in wind - rows 10 containing plastic fragments 12 spaced to a wetting truck 14 as well as a wind - row former / processor . the fragments of plastic bags are normally in segments to about 12 - 20 inches long . the compost is kept wet by a spray of water 18 on the pile from truck 14 and allowed to stand until sufficiently digested or mature for separation according to size . when mature or stabilized , the compost is transferred to a collection truck ( not shown ), which transports the compost to a vibrating screen separator 20 for segregation according to size . separator 20 consists of a non - blinding vibrating screen and associated means to deliver the compost to the screens and process it into &# 34 ; accept &# 34 ; and &# 34 ; reject &# 34 ;. it is preferred to employ a screen with a screen bed 22 containing flexible screen mats which are dynamically tensioned and slackened by a screen box driver unit ( s ) ( not shown ). the screen box is accelerated by 3 . 5 g , the bulk receives up to 50 g . this materially aids in preventing blinding or pegs . oscillation of the screen frame , which is similar to a ladder in construction , is caused by connection to rubber blocks at the screen deck 22 level , which in turn are activated by the vibration of the screen box ( not shown ). the rubber blocks act as spring elements for the oscillation system . operation is quite quiet with minimum vibration transmitted to the support structure . the screen mats are typically - full width formed of polyurethane and flexible oscillation systems , which operate at different amplitudes , but at the same frequency to generate the non - blinding action . the non - blinding vibrating screen system is described , for instance , in u . s . pat . nos . 4 , 169 , 788 to 5 , 062 , 949 incorporated herein by reference , and manufactured by aggregates equipment , inc . of leola , pa . the screen is inclined at an angle of about 20 ° and is divided into multiple , preferably three , zones . the first zone or zones separate out small sized particles and typically has a hole size of about 1 / 4 inch square ( 1 / 4 &# 34 ;× 1 / 4 &# 34 ;). smaller or larger holes can be employed . an intermediate zone contains holes of a larger size , typically 3 / 8 &# 34 ;× 3 / 8 &# 34 ; to 5 / 8 &# 34 ;× 5 / 8 &# 34 ; and more typically about 1 / 2 &# 34 ;× 1 / 2 &# 34 ;. the coarser zone typically contains screens of holes 3 / 4 &# 34 ;× 3 / 4 &# 34 ; to 1 &# 34 ;× 1 &# 34 ;. committed , particulate compost enters screen deck 22 from hopper 24 and passes through a zone a of finest screen size . from there , it passes through zone b of a larger screen size , and then to a larger screen size in zone c for final recovery of largest compost particles . maximum screen size may be anywhere from 1 / 2 &# 34 ;× 1 / 2 &# 34 ; to 1 &# 34 ;× 1 &# 34 ;, depending on the market . it is to be understood that more or less screen sections may be employed , but to no great advantage . after final separation , the oversized particles are passed to the discharge conduit 26 and deposited onto conveyer 28 for recycling to freshly made green waste to help initiate and promote the digestion of the green waste . the recycled compost is substantially free of plastic due to removal in an exhaust system and prevented thereby from concentrating in the green waste and , ultimately , the compost . one or more , preferably two ( 2 ) plenum chambers 30 and 32 are coupled to frame 34 positioned above the screen deck 22 and act in cooperation with a wheel blower system 36 and 38 to draw air through the bed of compost counter - current to the passage of compost through the screen . the air lifts the waste plastic fragments from the bed . the fragments are drawn by suction into the plenum chambers . the plenum chambers have converging walls which cause velocity to increase as the exhaust of the plenum chamber is approached . the plenum chambers typically have a length coextensive with a width of the screen deck and sealed to screen bed 22 with flexible rubber seals 40 and 42 . plenum chamber 30 has a width in machine direction of about three feet ( 3 &# 39 ;) and draws air through the bed of compost at a rate of about 5 to about 10 feet per second . plenum chamber 32 , by contrast , is smaller , having a width of about 2 feet ( 2 &# 39 ;) and draws air at higher velocity , of about 10 to about 15 feet per second . as depicted , the plenum chambers are positioned over the mid - section ( zone b ) of the bed so as not to draw in the finer sized compost from zone a . purification is typically completed by the time the compost reaches zone c . the plenum chambers could , however , extend into zone a and / or zone c . the waste plastic which is recovered is recycled or disposed of in a landfill . compost which passes through the screens is separately recovered or combined in conveyor 40 . the compost which passes through the screen is , as indicated , conveyed away from the screen deck , packaged and sold to the agricultural and horticultural markets . as indicated above , oversized particles goes back to the compost and mixed with the green waste to continue the digestion action to break down both the green waste and the oversize . in process , the screen size in zone a is sufficiently small to prevent plastic from entering the product . in zone b , the size of the compost is large enough not to enter the plenum chamber with the plastic while the suction and screen size inhibit plastic from passing through the screen . in the final zone , plastic may pass through the screen and contaminate the compost , but is removed ahead of that zone .	2
an embodiment of the present invention will be described hereinbelow with reference to the drawings . fig3 and 4 are block diagrams showing constructions of an embodiment of the invention . fig3 shows a coding circuit and fig4 shows a decoding circuit . in fig3 reference numeral 60 denotes a memory to store data , as a table , corresponding to check bits of cyclic codes for input data i 0 , i 1 , . . . , i k - 1 , and i k . when the data i 0 , i 1 , . . . , i k - 1 , and i k are input to addresses a 0 , a 1 , . . . , a k - 1 in the memory 60 , corresponding check bits r 0 , r 1 , . . . , r m - 1 are output from data outputs d 0 , d 1 , . . . , and d m - 1 . reference numeral 62 indicates a latch circuit for latching the input data i 0 , i 1 , . . . , i k - 1 , and i k and outputs of the memory 60 corresponding to them , that is , the check bits r 0 , r 1 , . . . , and r m - 1 and outputting as a code word . in fig4 reference numeral 64 indicates a memory of the same content as that of the memory 60 . when information bits of the code word including the error pattern which was received are input to the memory 64 , corresponding check bits are output therefrom . reference numeral 66 denotes a comparator of a bit unit for comparing the check bits of the code word including the error pattern which was received and the check bits from the memory 64 on a bit unit basis and outputting an error detection signal indicative of the presence or absence of error and the error position . as the result of the bit comparison by the comparator 66 , if all of the check bits coincide , respectively , it is decided that no error exists . fig5 is a block diagram showing a schematic construction of the main section of a processing circuit as the second embodiment of the invention in the case where the number of information bits constructing one code word and the number of check bits corresponding to the information bits are large . that is , fig5 shows modification examples of the portions of the memories 60 and 64 in the coding circuit of fig3 and the decoding circuit of fig4 . reference numerals 70 , 71 , 72 , and 73 denote memories for outputting the data regarding check bits , which will be explained hereinlater , for the address inputs . reference numerals 76 , 77 , 78 , and 79 indicate operating circuits for getting the exclusive or . in the example shown in the diagram , the check bits r 0 , r 1 , . . . , and r 7 of eight bits are generated for the inputs i 0 , i 1 , . . . , and i 19 of 20 bits . the arithmetic operations are based on the galois field and its theoretical background will now be described hereinbelow . there is the relation of the following equation between the input data i and the check bits r . ## equ1 ## the equation ( 9 ) is separated into four parts . ## equ2 ## since coefficients { g i , j } of the equation ( 10 ) are previously known , the relation of ( r 0 &# 39 ;, r 1 &# 39 ;, r 2 &# 39 ;, r 3 &# 39 ;) for ( i 0 , i 1 , . . . , i 9 ) is previously obtained . a data table such that when ( i 0 , i 1 , . . . , i 9 ) are input to the addresses , the output data of ( r 0 &# 39 ;, r 1 &# 39 ;, r 2 &# 39 ;, r 3 &# 39 ;) in the equation ( 10 ) can be obtained is stored into the memory 70 . similarly , data tables such as to provide the relations of the equations ( 11 ), ( 12 ), and ( 13 ) are respectively stored into the memories 71 , 72 , and 73 . the operations of the equation ( 14 ) are executed by the operating circuits 76 , 77 , 78 , and 79 , thereby obtaining the check bits ( r 0 , r 1 , . . . , r 7 ) as final objective values . fig6 is a block diagram showing a schematic construction of the main section in the embodiment in the cases where the number of information bits and the number of check bits are further increased than those in the case of fig5 and where the number of information bits is set to a × n and the number of check bits is set to b × m . in a manner similar to fig5 fig6 shows modification examples of the portions of the memories 60 and 64 in fig3 and 4 . as shown in the diagram , in the construction of fig6 ( a × b ) memories 80 to 88 similar to the memories 70 to 73 in fig5 are arranged like a matrix , the input information bits i 0 , . . . , and i an - 1 are divided into groups and the information bits of each group are input to address inputs of the memory of the same row . similar to fig5 the memories 80 to 88 output the data regarding the corresponding check bits . if outputs from the memories of the same column are calculated by exclusive or circuits 90 to 95 , the objective check bits r 0 , . . . , r bm - 1 can be obtained . in a manner similar to the case of fig4 according to the decoding circuit using the circuits shown in fig5 and 6 , in the constructions shown in fig5 and 6 , the check bits for the information bits in the reception code word are obtained and compared with the check bits in the reception code word by a bit comparator on a bit unit basis . with the above construction , since the data is processed in parallel , objective outputs can be obtained at a very high speed . on the other hand , since the apparatus does not depend on the bit rate , even a signal of a high bit rate can be also similarly processed at a high speed . as will be easily understood from the above description , according to the invention , the check bits for the information bits can be obtained at a high speed irrespective of the bit rate . thus , the data transmission of a high bit rate can be easily realized .	7
referring to fig3 there is shown a schematic block diagram of a single channel rotary transformer circuit for a vcr in accordance with the present invention . as shown in this drawing , the single channel rotary transformer circuit comprises a microcomputer 1 for generating a head switching signal and recording / playback flags to control recording / playback operations , a control signal oscillator 2 for generating a control oscillating signal in response to the head switching signal from the microcomputer 1 , an erase signal oscillator 3 for generating an erase oscillating signal in response to the recording / playback flags from the microcomputer 1 , and a first rotary transformer 4 for transferring a signal into which the control oscillating signal from the control signal oscillator 2 and the erase oscillating signal from the erase signal oscillator 3 are combined , to first and second band pass filters 9 and 6 and a power supply circuit 5 . the power supply circuit 5 is adapted to supply power to a drum rotating circuit ( not shown ) in response to an output signal from the first rotary transformer 4 . to this end , the power supply circuit 5 includes a diode 51 for rectifying the output signal from the first rotary transformer 4 , and a condenser 52 for smoothing the rectified signal from the diode 51 . the second band pass filter 6 is adapted to filter the output signal from the first rotary transformer 4 at an erase signal frequency band . the first band pass filter 9 is adapted to filter the output signal from the first rotary transformer 4 at a control signal frequency band . the single channel rotary transformer circuit further comprises an erase switch 7 being switched in response to an output signal from the second band pass filter 6 , an erase magnetic head 8 for erasing signals recorded on a magnetic tape in response to an output signal from the erase switch 7 , a frequency / voltage converter 10 for converting an output signal from the first band pass filter 9 into a voltage signal , a buffer 11 for buffering an output signal from the frequency / voltage converter 10 , a 2 - divider 12 for dividing a period of an output signal from the buffer 11 by 2 , and a head section 16 for recording signals on the magnetic tape and reading the signals recorded on the magnetic tape . an output signal from the 2 - divider 12 is applied as a switching control signal to first and second select switches 151 and 153 in a switching section 15 , and the output signal from the frequency / voltage converter 10 is applied as a switching control signal to a third select switch 152 in the switching section 15 . the head section 16 includes a plurality of magnetic heads a - d for recording the signals on the magnetic tape and reading the signals recorded on the magnetic tape . the switching section 15 is switched in response to the output signal from the buffer 11 and the output signal from the 2 - divider 12 to transfer an output signal from the head section 16 to a second rotary transformer 14 . also , the switching section 15 is switched in response to the output signal from the buffer 11 and the output signal from the 2 - divider 12 to transfer an output signal from the second rotary transformer 14 to the head section 16 . to this end , the switching section 15 includes the first to third select switches 151 , 153 and 152 . the first select switch 151 is switched in response to the output signal from the 2 - divider 12 to select one of output signals from the magnetic heads a and b in the head section 16 . the second select switch 153 is switched in response to the output signal from the 2 - divider 12 to select one of output signals from the magnetic heads c and d in the head section 16 . the third select switch 152 is switched in response to the output signal from the buffer 11 to select one of output signals from the first and second select switches 151 and 153 . the second rotary transformer 14 is adapted to transfer an output signal from the switching section 15 to a recording / playback amplifier circuit 13 having an amplifier . also , the second rotary transformer 14 transfers an output signal from the recording / playback amplifier 13 to the switching section 15 . the recording / playback amplifier circuit 13 is adapted to amplify an output signal from the second rotary transformer 14 by a predetermined level and output the amplified signal to an input / output terminal . also , the recording / playback amplifier circuit 13 amplifies an output signal from the input / output terminal by the predetermined level and outputs the amplified signal to the second rotary transformer 14 . the operation of the single channel rotary transformer circuit for the vcr with the above - mentioned construction in accordance with the present invention will hereinafter be described in detail with reference to fig4 a to 4i which are waveform diagrams of the output signals from the components in fig3 . first , in a playback mode , the magnetic heads a - d in the head section 16 travel on tracks of the magnetic tape to read sequentially the signals recorded on the magnetic tape . at this time , the microcomputer 1 , which controls the rotation of a head drum ( not shown ), outputs the head switching signal as shown in fig4 a to the control signal oscillator 2 . the microcomputer 1 also outputs the playback flag &# 34 ; 0 &# 34 ; to the erase signal oscillator 3 . when the head switching signal from the microcomputer 1 is high in logic , the control signal oscillator 2 outputs the control oscillating signal as shown in fig4 b . the erase signal oscillator 3 outputs a playback oscillating frequency signal fp in response to the playback flag &# 34 ; 0 &# 34 ; from the microcomputer 1 , the playback oscillating frequency signal fp having a frequency lower than that of a recording oscillating frequency signal fn . the control oscillating signal from the control signal oscillator 2 and the playback oscillating frequency signal fp from the erase signal oscillator 3 are combined as shown in fig4 c and then transferred through the first rotary transformer 4 to the first and second band pass filters 9 and 6 and the power supply circuit 5 . in the power supply circuit 5 , the combined signal is rectified by the diode 51 and smoothed by the condenser 52 . the resultant direct current ( referred to hereinafter as dc ) voltage signal is supplied to the drum rotating circuit . also , the combined signal is not filtered at a recording oscillating frequency band by the second band pass filter 6 . also , the combined signal is filtered at the control signal frequency band by the first band pass filter 9 and the resultant signal as shown in fig4 b is applied to the frequency / voltage converter 10 . the frequency / voltage converter 10 converts the output frequency signal from the first band pass filter 9 into the voltage signal as shown in fig4 d and outputs the converted voltage signal to the buffer 11 . the buffer 11 buffers the output signal from the frequency / voltage converter 10 and outputs the resultant signal as shown in fig4 e to the 2 - divider 12 and the third select switch 152 in the switching section 15 . the 2 - divider 12 divides the period of the output signal from the buffer 11 by 2 and outputs the resultant signal as shown in fig4 f to the first and second select switches 151 and 153 in the switching section 15 . when the output signal from the 2 - divider 12 as shown in fig4 f is high in logic , the first and second select switches 151 and 153 select the output signal from the magnetic head a and the output signal from the magnetic head c , respectively . on the contrary , when the output signal from the 2 - divider 12 as shown in fig4 f is low in logic , the first and second select switches 151 and 153 select the output signal from the magnetic head b and the output signal from the magnetic head d , respectively . as a result , the first and second select switches 151 and 153 output the resultant signals as shown in fig4 g and 4h to the third select switch 152 , respectively . also , when the output signal from the buffer 11 as shown in fig4 e is high in logic , the third select switch 152 selects the output signals from the magnetic heads a and b transferred through the first select switch 151 . on the contrary , when the output signal from the buffer 11 as shown in fig4 e is low in logic , the third select switch 152 selects the output signals from the magnetic heads c and d transferred through the second select switch 153 . as a result , the third select switch 152 outputs the resultant signal as shown in fig4 i to the second rotary transformer 14 . in result , the output signals from the magnetic heads a - d in the head section 16 are sequentially applied to the second rotary transformer 14 through the switching section 15 . then , the output signal from the switching section 15 as shown in fig4 i is transferred to the recording / playback amplifier circuit 13 through the second rotary transformer 14 . the recording / playback amplifier circuit 13 amplifies the output signal from the second rotary transformer 14 by the predetermined level and outputs the amplified signal to a video / audio processing circuit ( not shown ) through the input / output terminal . on the other hand , in a recording mode , the microcomputer 1 , which controls the rotation of the head drum ( not shown ), outputs the head switching signal as shown in fig4 a to the control signal oscillator 2 . the microcomputer 1 also outputs the recording flag &# 34 ; 1 &# 34 ; to the erase signal oscillator 3 . when the head switching signal from the microcomputer 1 is high in logic , the control signal oscillator 2 outputs the control oscillating signal as shown in fig4 b . the erase signal oscillator 3 outputs the recording oscillating frequency signal fn in response to the recording flag &# 34 ; 1 &# 34 ; from the microcomputer 1 . the control oscillating signal from the control signal oscillator 2 and the recording oscillating frequency signal fn from the erase signal oscillator 3 are combined as shown in fig4 c and then transferred through the first rotary transformer 4 to the first and second band pass filters 9 and 6 and the power supply circuit 5 . in the power supply circuit 5 , the combined signal is rectified by the diode 51 and smoothed by the condenser 52 . the resultant dc voltage signal is supplied to the drum rotating circuit . also , the combined signal is filtered at the recording oscillating frequency band by the second band pass filter 6 , thereby causing the erase switch 7 to be turned on . as the erase switch 7 is turned on , the erase magnetic head 8 erases the signals recorded on the magnetic tape . also , the combined signal is filtered at the control signal frequency band by the first band pass filter 9 and then applied as the switching control signals to the first to third select switches 151 , 153 and 152 in the switching section 15 in the same manner as that in the playback mode . on the other hand , an output signal from the video / audio processing circuit ( not shown ) is applied to the recording / playback amplifier circuit 13 through the input / output terminal . the output signal from the video / audio processing circuit is amplified by the predetermined level by the recording / playback amplifier circuit 13 and then applied to the switching section 15 through the second rotary transformer 14 . in the switching section 15 , the first to third select switches 151 , 153 and 152 are switched in response to the output signal from the 2 - divider 12 and the output signal from the buffer 11 to drive the corresponding magnetic hems . as a result , the output signal from the video / audio processing circuit is recorded on the magnetic tape . as apparent from the above description , according to the present invention , the single channel rotary transformer circuit is capable of switching the plurality of magnetic heads to transmit the recording / playback signals to / from the magnetic heads through the single channel . therefore , an rf circuit can be simplified in construction as compared with the conventional multi - channel rotary transformer circuit . also , there is no necessity for designing a short ring to shield an inter - channel signal interference . further , the reduced number of recording / playback amplifiers has the effect of reducing the manufacturing cost . although the preferred embodiments of the present invention have been disclosed for illustrative purposes , those skilled in the art will appreciate that various modifications , additions and substitutions are possible , without departing from the scope and spirit of the invention as disclosed in the accompanying claims .	6
we turn now to the circuitry and operation of a preferred embodiment of the invention , after first briefly describing the drawings . fig1 is a block diagram of the circuitry embodying this invention . fig2 is a circuit diagram of a single stage of a low pass filter . fig3 is a circuit diagram of a single stage of a high pass filter . fig4 is a timing diagram of the input and output of a modulator . referring to fig1 the muscle fatigue monitor circuit is shown generally at 10 . a myoelectric signal is detected by differential surface electrodes 12 and transmitted to preamplifier 14 . preamplifier 14 first filters the myoelectric signal to remove noise and low frequency artifacts caused by body movements and then amplifies the signal . the output from preamplifier 14 is simultaneously fed to modulated low pass and high pass filters 16 , 18 . each filter has a series of five identical stages . the first stage 20 for the low pass filter is shown in fig2 . the signal passes through a pair of switches 24 , 25 ( when closed ) and a pair of identical resistors 27 , 28 to an input of operational amplifier 30 . identical capacitors 32 , 33 form a double - pole rc filter with resistors 27 , 28 , which determines the cutoff frequency fc of the filter stage according to the following equation : as the rc value is constant , the cutoff frequency is actually a function of n , the duty cycle , which is directly proportional to the length of time switches 24 , 25 remain closed during a cycle . trim resistors 35 , 36 control the spectral characteristics of stage 20 . first stage 40 for high pass filter 18 is shown in fig3 . the signal from preamplifier 14 passes through a pair of identical , series - connected capacitors 44 , 45 to an input of operational amplifier 47 . switches 49 , 50 connect a pair of resistors 52 , 53 to corresponding capacitors 44 , 45 , and the cutoff frequency of stage 40 is governed by the same equation as with low pass filter stage 20 . trim resistors 55 , 56 control the spectral characteristics of stage 40 . low pass filter 16 has the same cutoff frequency as high pass filter 18 for all values of the duty cycle . both filters 16 , 18 have very sharp roll - offs of about 60 db per octave , and their resistor and capacitor values are correspondingly equal so that filter characteristics are independent of any change in cutoff frequency . filters 16 , 18 introduce a gain of about ten . the output signal of high pass filter 18 is fed to fixed low pass filter 60 , which removes the high frequency artifacts created by the filter &# 39 ; s switches . as fixed low pass filter 60 introduces its own gain of about ten , an attenuator 61 is used as a pre - stage to reduce the incoming signal by the same factor . the gain of filter 60 therefore restores its output signal to a level equal to the output signal of low pass filter 16 . the signals from filters 16 , 60 are fed into identical rms circuits 70 , 71 , which calculate true rms voltage . rms circuits 70 , 71 have unity gain amplifiers 72 , 73 as first stages , which provide the input signals for rms modules 75 , 76 . amplifiers 72 , 73 remove any d . c . offsets introduced by the amplifiers of filters 16 , 18 , and 60 . such offsets would otherwise be erroneously added to the rms circuits &# 39 ; output , as each rms module 75 , 76 continuously sends out an rms voltage corresponding to the magnitude of the filtered input signal it receives . a four position switch 77 having multiple poles is connected to rms modules 75 , 76 of the rms circuits 70 , 71 . two poles connect a different capacitance 81 - 84 to rms modules 75 , 76 and thereby enables time constant of 0 . 1 , 0 . 5 , 2 . 83 or 10 . 0 seconds to be selected for a given test . six other poles are used to maintain the gains and offsets of the circuits . the outputs of rms circuits 70 , 71 are fed through switches 78 , 79 ( when closed ) to difference amplifier 80 , the output of which is proportional to the difference between its two rms voltage inputs . the gain of amplifier 80 is externally adjustable through two poles of switch 77 . the gain is adjusted by the poles to keep dynamic performance constant relative to the selected time constant . the output from amplifier 80 is sent to differentiator 85 and one input of summing amplifier 86 . differentiator 85 produces an initially large , transient voltage for an abrupt change in input voltage . the differentiator &# 39 ; s output is fed to the other input of summing amplifier 86 . the addition of the differentiated voltage into this circuitry which controls the response of the monitor ( as hereinafter explained ) improves the dynamic responses of the monitor by a factor of about four . summing amplifier 86 combines the differentiator &# 39 ; s and the difference amplifier &# 39 ; s outputs . the sum of these voltages is then fed to integrator 87 which produces a slowly varying d . c . voltage corresponding to the integral of the difference between the high - filtered and low - filtered rms voltages and the differentiated value of said difference . the integrated output is fed through sample and hold circuit 88 ( to be discussed later ) to comparator 92 of the modulator 90 . the other input for comparator 92 is from triangle wave generator 94 which operates at about 20 khz . the integrator signal of fig4 is greatly time - compressed as it has a much lower frequency content than that of the triangle wave . therefore , changes in pulse width and duty cycle would occur more gradually than represented . as shown in the timing diagram of fig4 the output of comparator 92 is a pulse width modulated ( pwm ) signal or pulse train , the pulse width ( and hence the duty cycle ) of which increases or decreases with a corresponding change in the level of the integrator output . the pwm signal is fed to low and high pass filters 16 , 18 . the output from sample and hold circuit 88 is also fed to band pass filter 98 which eliminates the d . c . level and sends an amplified a . c . output to zero detector 100 . placement of band pass filter 98 after sample and hold circuit 88 insures stable operation when monitor is used in the hold mode ( as hereinafter explained ). zero detector 100 feeds an input signal from band pass filter 98 into a pair of matched comparators 101 , 102 and sends out the resulting signal to clock 104 . as long as no voltage is received from zero detector 100 , clock 104 provides high frequency clocking pulses for sample and hold circuit 88 . the clocking pulses repeatedly enable the sample and hold circuit 88 , thus passing a staircased version of the output of integrator 87 to modulator 90 . the output of zero detector 100 is also fed to switches 78 , 79 , alternate light circuit 108 , and event marker driver circuit 114 . when the integrator output continues to have significant a . c . variation , no zero is detected . red light 109 of light circuit 108 is lit , and switches 78 , 79 remain closed . if there is no a . c . variation from integrator 87 , zero detector 100 produces an output voltage . green light 110 turns on , and switches 78 , 79 are open . driver circuit 114 enables the event marker of a gulton rustrack # 500 strip chart recorder 112 . recorder 112 also has scale select switch 116 , which controls the recorder chart scale , and a chart drive switch 118 , which selectively enables the chart movement of recorder 112 . the rms circuits 70 , 71 also need their respective outputs to meter switch 120 and meter 122 . meter switch 120 is a two - pole , three - position switch which selectively forwards either high or low filtered rms voltage or their difference to meter circuit 122 . meter circuit 122 amplifies the signal from meter switch 120 and sends it to meter 124 for visual display . the same rms outputs are also fed to mode switch 126 , which when closed , feeds the rms voltage to divider circuit 128 . divider circuit 128 produces an output signal which represents the ratio of the two rms voltages . this ratio output is amplified and sent to analog switch 130 . analog switch 130 sets its ratio output to 1 until an initial signal is received . the ratio output of analog switch 130 is sent to recorder &# 39 ; s parameter switch 132 . parameter switch 132 also receives the output from sample and hold circuit 88 , and either signal can be selected for print out on the recorder 112 . referring to fig1 surface electrodes 12 are connected to a patient &# 39 ; s muscle . a cutoff frequency is selected for filters 16 , 18 . this selected frequency is usually about 90 hz , which is in the mid - range of possible median myoelectric frequencies . when the monitor is activated , the actual myoelectric signal is sensed by electrodes 12 and sent through preamplifier 14 to low and high pass filters 16 , 18 . if the actual median frequency of the myoelectric signal is above or below the selected cutoff frequency , the low and high filters &# 39 ; rms voltages from rms circuits 70 , 71 will not be the same . when the rms difference is zero the cutoff frequency of the filters approximately equals the true median frequency . switches 78 , 79 are initially closed , and the different rms voltages are fed into amplifier 80 . the amplifier output represents the difference between the rms voltages . if the low pass filter &# 39 ; s output is greater than the high pass filter &# 39 ; s output , the output of difference amplifier 80 has a negative value . if the opposite were the case , the amplifier output would be positive . this signal passes through differentiator 85 and summing amplifier 86 . integrator 87 then produces the slowly varying d . c . signal which is fed to modulator 90 , because sample and hold circuit 88 is initially continuously enabled . the modulator combines the integrator output with the triangle wave to produce a 20 khz pulse train which is fed to the switches of filters 16 , 18 . the filter switches close when they receive a pulse and open for a period of zero voltage . as previously explained , the duty cycle and hence the filters &# 39 ; cutoff frequency directly depend on the length of &# 34 ; on &# 34 ; time for the switches , and as shown in fig4 the level of the integrator output determines this pulse width or &# 34 ; on &# 34 ; time . based on the pulse width of the modulator output signal , the filters &# 39 ; cutoff frequency increases or decreases toward the actual median frequency . the rms voltages are compared again and the difference is less . integrator 87 integrates the new difference to the old , and the cutoff frequency is increased or decreased again towards the real median . this is a continuous process which forces the cutoff frequency of the filters toward close approximation of the true median frequency . in the event the modulator output raises or lowers the filters &# 39 ; cutoff frequency past the actual median , the output of difference amplifier 80 will change sign . the new output will reduce the integrator output thereby correcting the overshoot . the monitor can operate in a track mode in which the sample and hold circuit 88 is continually enabled , and switches 78 , 79 remained closed throughout the test . the track plot records the cutoff frequency of filters 16 , 18 . the filters &# 39 ; cutoff frequency is continually displayed as it decreases as the median frequency decreases . the decrease in frequency can be real - time recorded in this manner and directly observed as it occurs . the resulting track mode plot can be directly read for median frequency at any given point . the track plot is also not susceptable to amplitude changes which invariably occur due to a number of factors including patient movement . finally , track plots for successive tests can be easily compared . there is a fall off at the beginning of each muscle contraction . this is clearly shown by the track plots even if the readouts for different tests were not started at the same time . the monitor can also function in a hold mode . there , zero detector 100 disables clock 104 when it senses the absence of substantial a . c . variation from the integrator 87 . sample and hold circuit 88 then blocks any signal from integrator 87 and holds the last previous value . at the same time , zero detector 100 switches 78 , 79 cutting off any further rms voltages from rms circuits 70 , 71 . the cutoff frequency of the filters of the now - balanced monitor is fixed at the initial median frequency . the median frequency of the myoelectric signal decreases as the muscle is fatigued , however , and low pass filter therefore passes increasingly more of the entire signal . as the test progresses , the high filtered voltage decreases with respect to the low filtered voltage . the difference can be seen visually at meter 124 or on the chart of recorder 112 . in one embodiment the two voltages are respectively plotted along x and y axes of a graph , with the resulting polar vector representing the magnitude of the overall myoelectric signal . alternatively , the ratio of the voltages can be plotted as a function of time .	0
some examples of the present invention will be described below in the specification with reference to illustrative drawings . it should be noted that each reference numerals in the drawings are to be meant to indicate the same element when the numeral is the same although present in different drawings . also , in explaining the examples of the present invention in the specification , detailed description on the well - known constructing element or functions related to the invention will be omitted when the specific explanation can obscure the features of the present invention . also , if a component is referred to be “ linked ”, “ coupled ” or “ connected ” to another component in describing construction component of the present invention , the component may be directly linked or connected to the other component , or a third component may intervene to “ link ”, “ couple ” or “ connect ” the two components . fig1 is a block diagram illustrating a 3d image processing unit . referring to fig1 , the 3d image processing unit comprises an input unit 100 , an inverse - multiplexing unit 110 , a video decoding unit 120 , a 3d image synchronizing unit 130 , a 3d image compositing unit 140 , a video output unit 150 , an audio decoding unit 160 and an audio output unit 170 . the input unit 100 receives input of 3d images from outside . more specifically , the input unit 100 receives input of transmission stream including 3d image data , and transmits the input to an inverse - multiplexing unit . the inverse - multiplexing unit 110 separates audio and video . more specifically , the inverse - multiplexing unit 110 can separate basic stream ( s ) on audio and basic stream ( s ) on video from the transmission stream and , in the case of 3d image broadcasting , can separate basic stream on multiple constituent videos ( images ). the video decoding unit 120 decodes the basic stream ( s ) on video . the video decoding unit 120 can include a first video decoding unit 121 and a second video decoding unit 122 . the first video decoding unit 121 can decode the basic stream on the first image constituting the 3d image to generate a first image ( data ), and the second video decoding unit 122 can decode the basic stream on the second image , which constitutes the 3d image and related to the first image , to generate a second image ( data ). for example , when the 3d image is consist of a dual stream with one basic stream on the reference image and the other basic stream on the additional image , the first video decoding unit 121 can decode the basic stream on the reference image to generate a reference image , and the second video decoding unit 122 can decode the basic stream on the additional image to generate on additional image . the audio decoding unit 160 decodes the basic stream ( s ) on audio and generates audio ( data ), and the audio output unit 170 outputs the audio data generated . the 3d image synchronizing unit 130 synchronizes the decoded first image and the second image at the video decoding unit 120 . the 3d image compositing unit 140 generates 3d image ( data ) on the basis of the synchronized first and second images , and outputs the images on a display means through the video output unit 150 . the 3d image compositing unit 140 generates the 3d image data in the format of side - by - side or frame packing depending on the format supported by the video output unit 150 , and outputs the images on a displaying means through the video output unit 150 . for example , the first image can be a reference image and the second image an additional image . when the first video decoding unit 121 decodes the basic stream on the reference image to generate a reference image and the second video decoding unit 122 decodes the basic stream on the additional image to generate an additional image , mpeg - 2 video encoding method can be used at the first video decoding unit 121 and encoding methods producing high quality video such as h . 264 or hevc ( high efficiency video coding ) can be used at the second video decoding unit 122 . the h . 264 video encoding method generally shows two times higher compression efficiency compared to mpeg - 2 video encoding method , and the hevc video method shows four times higher compression efficiency compared to mpeg - 2 video method . therefore , when a broadcasting station ( server ) transmits dual stream - based 3d image broadcasting , h . 264 encoded stream can have 12 mbps of data rates if mpeg - 2 encoded stream has 6 mbps of data rates . in other words , under the same channel noise environment , the chances of error when transmitting mpeg - 2 encoded data is about two times higher compared to the chances of error when transmitting h . 264 encoded data . the present invention , considering the features that occurrence of errors in multiple images constituting a 3d image is not homogeneous among images , proposes a method of enhancing the quality of 3d images by correcting ( or compensating ) the error of one image by using the other image in which error has not occurred from multiple images constituting a 3d image . fig2 is a block diagram illustrating a 3d image processing unit according to one example of the present invention . referring to fig2 , the 3d image processing unit according to the present invention comprises an input unit 200 , an inverse - multiplexing unit 210 , a video decoding unit 220 , a 3d image synchronizing unit 230 , a 3d image correcting unit 235 , a 3d image compositing unit 240 , a video output unit 250 , an audio decoding unit 260 and an audio output unit 270 . the video decoding unit 220 includes a first video decoding unit 221 and a second video decoding unit 222 . the operations of the input unit 200 , the inverse - multiplexing unit 210 , the video decoding unit 220 , the 3d image synchronizing unit 230 , the audio decoding unit 260 and the audio output unit 270 are the same as the operations of the devices described with reference to fig2 and detailed explanation is omitted . the 3d image processing unit according to the present invention further includes a 3d image correcting unit 235 . the 3d image correcting unit 235 performs the step of error correction on the basis of the first and second images synchronized at the 3d image synchronizing unit 230 . the step of error correction includes checking the error and , when error is detected , correcting the error of the data of the image which contains the error on the basis of other image in which error is not detected . when error is detected in the first image ( or one block of the first image ), for example , the error in the first image ( or one block of the first image ) can be corrected on the basis of the second image ( or corresponding block of the second image ). when error is detected in the second image ( or one block of the second image ), as another example , the error in the second image ( or one block of the second image ) can be corrected on the basis of the first image ( or corresponding block of the first image ). the 3d image compositing unit 240 generates a 3d image on the basis of the reference image and additional image for which error correction has been performed , and outputs the 3d image on a display means through the video output unit 150 . the process of correcting errors performed at the 3d image correcting unit 235 can be performed as follows . fig3 is a flow diagram illustrating the process of error correction by the 3d image correcting unit according to one example of the present invention . in the description below , the case where error is detected in the first image among multiple images constituting the 3d image will be described as an example . it is obvious that the first image can be one arbitrary image of multiple images 3d image . for example , the first image can be a reference image constituting the stereoscopic image or the first image can be an additional . also , when three or more images constitute the 3d image , for example , the first image can be one of the three or more images . referring to fig3 , the 3d image correcting unit detects ( or checks ) errors on the first image constituting a 3d image in block unit ( or pixel unit ) of the image ( s 300 ). the error detection can be performed by using the characteristics of the basic stream of corresponding image itself or can be performed by comparing the pixel values of corresponding image decoded or by comparing the values of pixel blocks . as one example , if the first image is a reference image encoded by mpeg - 2 , the 3d image correcting unit can detect errors by comparing the level ( value ) in macro block unit of n × n pixels ( for example 8 × 8 pixels ) on the image decoded by mpeg - 2 . explaining more specifically , dc ( direct current ) coefficient included in dct ( discrete cosine transform ) coefficient as respective macro block unit of decoded image data is compared with dc coefficients of adjacent blocks to check whether the coefficient is within a certain range of values , and if the coefficient is not within the certain range of values , the macro block can be determined to contain errors . in other words , after extracting dc of each macro block unit , dc level of one block is compared to those of adjacent blocks and if the dc level is not within a certain range , the block can be detected ( or determined ) as an error block in which an error is occurred . in this case , the 3d image correcting unit can detect error blocks in the way shown in table 1 . referring to table 1 , x represents a certain block and neighbor ( x ) adjacent blocks around x ( for example 8 blocks surrounding the block x ). in the table , y represents the block among the adjacent blocks represented by neighbor ( x ), which is most similar to the block x in dc level . also , dis ( x , y ) represents the distance of similarity between the dc level of block x and the dc level of block y , and t represents the value of certain limit . in other words , the block x can be determined as an error block if the distance of similarity between the dc level of block y , which is the adjacent block with the closest dc level to the block x , and the dc level of block x is larger than the limit value of t . when the 3d image correcting unit detects error in macro block unit , detection of error can be easily performed with shorter time for correction . when the 3d image correcting unit detects an error block ( or pixel ) containing an error in the first image , the unit searches a corresponding block ( or pixel ) which corresponds to the error block in the second image related to the first image ( s 310 ). when the first image is a reference image decoded by mpeg - 2 and the second image is an additional image decoded by h . 264 ( or hevc ), for example , and if an error block is detected in the macro block unit of n × n pixels ( for example , 8 × 8 pixels ) on the reference image , comparison can be made on the macro block unit of n × n pixels ( for example , 8 × 8 pixels ) on the additional image . first , the 3d image correcting unit calculates correlation between the macro blocks on the first image and the macro blocks on the second image related to the first image to calculate disparity at the block unit . the calculation of correlation between the macro blocks on the first image and the macro blocks on the second image can be performed by using general 3 dimensional stereo matching method . as one example , dc level ( value ) of each block can be used as the value of each block of the macro blocks of the first image and the macro blocks of the second image . for example , considering each block as one pixel , disparity between two blocks can be represented as mathematical formula 1 , and the value of disparity can be calculated by using the value with the minimum cost among adjacent pixels . e ( x , y , d )=\| i 1 ( x + d , y )− i 2 ( x , y )\| [ mathematical formula 1 ] referring to mathematical formula 1 , i 1 is the value of the block ( or pixel ) of the first image , i 2 the block ( or pixel ) of the second image , ( x , y ) a variable representing the spatial coordinate of blocks ( or pixels ), d the disparity representing spatial distance between two corresponding blocks ( or pixels ) and e the cost . the 3d image correcting unit can calculate the value of disparity by using the value with minimum cost on the basis of the mathematical formula 1 . then , the 3d image correcting unit can search corresponding block in the second image , in which error has not been occurred , by using disparities of blocks excluding error block of the first image ( for example , reference image ), in which the error has occurred , and the blocks of the second image ( for example , additional image ) related to the first image . fig4 illustrates the process of searching the block corresponding to an error block according to one example of the present invention . in the figure , it is assumed that ( a ) represents the macro blocks on the first image and ( b ) represents the macro blocks on the second image . in fig4 , assuming that the area with oblique lines in ( a ), which is the blocks on the first image , is an error block 400 , corresponding block 410 can be searched in ( b ), which is the blocks on the second image , through the disparities of adjacent blocks ( 401 , 402 , 403 , 404 , 405 , 406 , 407 , 408 ). referring to fig3 again , the 3d image correcting unit corrects the error block ( or pixel ) of the first image , in which an error has occurred , on the basis of the block ( or pixel ) information of the corresponding block ( or pixel ) related to the first image ( s 320 ). here , correction of the block in which an error has occurred includes correcting the error pixel in the block in which the error has occurred . the 3d image correcting unit can correct the error block on the basis of the block information of the corresponding block when the amount of disparity change of the error block and the amount of disparity change of the corresponding block is not similar . in other words , the 3d image correcting unit can correct the error block on the basis of the block information of the corresponding block when the difference between the amount of disparity change , which is measured between the adjacent blocks of said error block and said error block , and the amount of disparity change , which is measured between the adjacent blocks of said corresponding block and said corresponding block , is greater than a certain value . here , the amount of disparity change can mean the amount of disparity change between the corresponding block and adjacent blocks . in the above one example , when the value of disparity at the same block of previous frame exists in the step of searching the corresponding block , the value can be used for reference . for example , when the value of a block except the error block is similar to the value of previous frame , the value of disparity calculated in previous frame can be used as the value of disparity of current block . also , the 3d image correcting unit can correct the error block on the basis of the color of the corresponding block or the difference in colors with adjacent blocks of the corresponding block when the difference in colors of the error block and adjacent blocks of the error block is not similar to the difference in colors of the corresponding block and adjacent blocks of the corresponding block . the 3d image correcting unit can correct the error block by simply copying the color of the corresponding block to the error block , or can correct the error block on the basis of the difference in colors between the corresponding block and adjacent blocks of the corresponding block . fig5 is a block diagram illustrating a 3d image processing unit according to one example of the present invention . referring to fig5 , the 3d image correcting unit 50 , which performs error correction on the first and second images constituting the 3d image , includes an error block detector 500 , a corresponding block searcher 510 and a corrector 520 . the error block detector 500 determines errors of the first image in block unit and detects an error block . the error block detector 500 can detect an error block by extracting dc level from the macro block unit of n × n pixels of the first image and comparing dc level of a certain block to dc level of adjacent blocks . for example , the macro block unit of n × n pixels of the first image includes the case of the macro block unit of 8 × 8 pixels of the first image . also , the error block detector 500 can detect a certain block as the error block when the difference of the dc level of the certain block and the dc level of the block having the dc level which is closest to the dc level of the certain block among the adjacent blocks of the certain block is greater than predetermined limit , as described in table 1 . the corresponding block searcher 510 searches the corresponding block which corresponds to the error block detected in the second image . the corresponding block searcher 510 can calculate the disparity at the macro block unit of n × n pixels of the first image and the macro block unit of n × n pixels of the second image , and search the corresponding block in the second image on the basis of the disparity at the block unit . in this case , the corresponding block searcher 510 can calculate the disparity by using the mathematical formula 1 . the corrector 520 corrects the error of the error block on the basis of the block information of the corresponding block . the corrector 520 can correct the error block by copying the colors of the corresponding block to the error block . also , the corrector 520 can correct the error block on the basis of the difference in colors between the corresponding block and adjacent blocks of the corresponding block . fig6 illustrates the process of processing a 3d image according to one example of the present invention . the 3d image processing unit synchronizes the first and second images constituting the 3d image ( s 600 ). the 3d image processing unit detects an error block in the first image ( s 610 ). the 3d image processing unit extracts dc level from macro block unit ( for example , macro block unit of 8 × 8 pixels ) of n × n pixels of the first image , and can detect the error block by comparing dc level of a certain block to dc level of adjacent blocks . for example , as described with respect to table 1 , the 3d image processing unit can detect a certain block as the error block when the difference of the dc level of the certain block and the dc level of the block having the dc level which is closest to the dc level of the certain block among the adjacent blocks of the certain block is greater than predetermined amount . the 3d image processing unit searches the corresponding block which corresponds to the error block in the second image ( s 620 ). the 3d image processing unit , in searching the corresponding block , can calculate the disparity at the macro block unit of n × n pixels of the first image and the macro block unit of n × n pixels of the second image , and can search the corresponding block in the second image on the basis of the disparity at the block unit . in this case , the 3d image processing unit can calculate the disparity by using the mathematical formula 1 described above . the 3d image processing unit corrects the error block on the basis of the block information of the corresponding block ( s 630 ). the 3d image processing unit can correct the error block by copying the colors of the corresponding block to the error block . also , the 3d image processing unit can correct the error block on the basis of the difference in colors between the corresponding block and adjacent blocks of the corresponding block . also , the 3d image correcting device can correct the error block on the basis of the block information of the corresponding block only when the difference between the amount of disparity change , which is measured between the adjacent blocks of the error block and the error block , and the amount of disparity change , which is measured between the adjacent blocks of the corresponding block and the corresponding block , is greater than predetermined value . also , the 3d image processing unit can correct the error block on the basis of the color of the corresponding block or the difference in colors with adjacent blocks of the corresponding block when the difference in colors of the error block and adjacent blocks of the error block is not similar to the difference in colors between the corresponding block and adjacent blocks of the corresponding block . the 3d image processing unit generates the 3d image by compositing the first image the error block corrected and the second image ( s 640 ). the 3d image processing unit can generate a 3d image with error corrected . the devices and the system including thereof can be implemented by hardware , software and the combination thereof . in the case of hardware implementation , the module used for recording broadcast program can be implemented by one or more application specific ic ( asic ), digital signal processor ( dsp ), digital signal processing unit ( dspd ), programmable logic device ( pld ), field programmable gate array ( fpga ), processor , controller , micro - controller , microprocessor , or other electronic unit designed to perform the functions described in the specification , or by combination thereof . software can be used to implement the module performing the functions described in the specification . software codes can be stored in a memory unit and executed by a processor . the memory unit can be implemented inside or outside the processor , and when implemented outside the processor , the memory can be connected to the processor through well - known connecting means . meanwhile , the method of the present invention described above can be implemented by a computer program . and the code or code segment constituting the program can be easily inferred by computer programmers in the field . also , the produced computer program can be stored in recording media ( information storing media ) that can be read by a computer , and executed by the computer , thereby implementing the method of the present invention . and , the recording media include all forms of recording media that can be read by a computer ( including intangible media such as carrier wave as well as tangible media such as cd and dvd ). it should be appreciated that the above description has been made to illustrate the technical idea of the present invention , and can be corrected and modified within the scope of the essential features of the present invention by those skilled in the art to which the present invention pertains to . therefore , the examples in the specification of the present invention should be considered not to limit the technical idea of the present invention but illustrate the present invention . in sum , and the present invention shall not be limited by the examples but shall be interpreted by the claims attached in terms of the scope of the invention , and any technical ideas equivalent to that of the present invention shall be considered to be within the scope of the present invention .	7
the present invention provides that the activation of mir - 221 and mir - 222 is regulated , at least in part , by the met oncogene and the c - jun transcription factor , and which , in turn , down - regulates pten and timp3 . activation of met signaling is a frequent genetic event observed in liver and lung cancer development . ap - 1 is a complex of dimeric basic region - leucine zipper proteins that belong to the jun ( c - jun , junb , jund ), fos ( c - fos , fosb , fra - 1 and fra - 2 ), maf and atf subfamilies c - jun is the most potent transcriptional activator in its group , whose transcriptional activity is attenuated and sometimes antagonized by junb . the fos proteins , which cannot homodimerize , form stable heterodimers with jun proteins and thereby enhance their dna binding activity . the present inventors focused on these two ap - 1 subfamilies , and in particular on c - jun and c - fos , although they found by bioinformatics search ( tess database ) that also atf - 1 and jund , could be potential transcription factors involved in mir - 221 and mir - 222 activation . the present invention demonstrates that c - jun and not c - fos is involved in mir - 221 and mir - 222 activation and that c - jun has one binding site in the mir - 221 / mir - 222 promoter region . the induction of ap - 1 is mostly mediated by the jnk cascades . by using anisomycin , an antibiotic which activates the jnk cascade , the inventors found an increase of mir - 221 / mir - 222 expression in huh7 hepatocarcinoma cells , as consequence of c - jun phosphorylation . intriguingly , when the inventors grew huh7 cells in serum free medium , they did not observe any variation in the expression level of mir - 221 and mir - 222 or pten and timp3 , showing that met activation is important for mir - 221 and mir - 222 transcription regulation and subsequent cellular migration . to address this issue the inventors investigated calu - 1 and snu - 387 cell migration and invasion after met silencing . migratory and invasive capabilities of both cell lines were reduced after met oncogene silencing ( fig1 a - 17b ). furthermore , a xenograft model of calu - 1 cells in which c - met was silenced by using an shmet plasmid ( fig1 c ), showed that mice injected with calu - 1 shmet cells are more sensitive to trail inducing apoptosis compared to the mice injected with the sh control ( fig1 d - 17e ). thus met confers not only a tumor growth advantage but also resistance to trail - inducing apoptosis over control tumors in vivo . therefore , met oncogene regulates mir - 221 and mir - 222 levels and , accordingly , cellular invasion and migration through c - jun transcription factor and jnk activation ( fig8 ). taken together , these data highlight a mechanism , involving met , through which mir - 221 and mir - 222 promote tumorigenesis and metastasis . thus approaches targeting met receptor and / or mir - 221 and mir - 222 in order to sensitize nsclc and hcc to trail - inducing apoptosis , but also in the prevention and inhibition of lung cancer and hepatocellular carcinoma , are included in the present invention . in the present invention , there are identified major mrna targets and signaling pathways that mediate mir - 221 and mir - 222 regulation in a wide panel of nsclc and hcc - derived cell lines . in vitro and in vivo experiments reveal that elevated levels of mir - 221 and mir - 222 in nsclcs and hccs correlates with pten and timp3 down - regulation , indicating that these two micrornas are a causal factor in the down - regulation of pten and timp3 in these types of cancers . the inventors examined the effects of mir - 221 and mir - 222 and their targets on cell survival and trail resistance . interestingly , the inventors found that after mir - 221 / mir - 222 enforced expression , or pten and timp3 down regulation , trail - sensitive nsclc and hcc cells became resistant to trail - inducing apoptosis , although pten down regulation was slightly more effective than that of timp3 . the present invention provides methods to affect mir - 221 and mir222 expression , since it is now proved that mir - 221 and mir - 222 expression is a “ prerequisite ” of trail - resistant nsclc and hcc cells . importantly , tumor stratification , on the basis of mir - 221 / mir - 222 expression levels , could be used as prognostic tool to predict trail - sensitivity or trail - resistance in the treatment of nsclcs and hccs . the present invention also discloses that mir - 221 and mir - 222 block pten expression leading to activation of the akt pathway , showing that mir - 221 and mir - 222 plays an important role in cell growth and invasiveness by targeting the pten / akt pathway . in this regard , cell cycle analysis evidenced an increase in cell growth tightly linked to the g1 to s shift , which is in agreement with modulation of pten and also of p27kip1 , a known regulator of the g1 / s cell cycle checkpoint and a downstream effector of pten . nsclc and hcc cells overexpressing mir - 221 and mir - 222 are not only trail - resistant but they also show an increase in migration and invasion capabilities , compared to cells expressing lower levels of mir - 221 and mir - 222 cells . moreover , mir - 221 and mir - 222 are herein shown to promote cell migration , invasion and growth via direct repression of pten and timp3 expression and of downstream pathways involving akt and erks phosphorylation , and the activation of mmp - 3 and mmp - 9 . further , pten and timp3 loss in h460 tumor xenograft conferred not only a significant tumor growth advantage but also a resistance to trail - inducing apoptosis over control tumors also in vivo . interestingly , the timp3 knockdown tumors were more vascularized than the control tumors , highlighting its role in angiogenesis and tumor formation . the identification of mir - 221 and mir - 222 as important regulators of tumor cell proliferation , migration , and invasion of nsclc and hcc , in vitro and in vivo , provides insights into the role of these mirnas in hepatic and lung oncogenesis and tumor behavior . the effects of mir - 221 and mir - 222 and their targets on cell survival and trail resistance were examined . interestingly , after mir - 221 / mir - 222 enforced expression , or pten and timp3 downregulation , trail - sensitive nsclc and hcc cells became resistant to trail - inducing apoptosis , although pten down regulation was slightly more effective than that of timp3 . this indicates that mir - 221 and mir - 222 overexpression is a “ prerequisite ” of trail - resistant nsclc and hcc cells . importantly , tumor stratification , on the basis of mir - 221 / mir - 222 expression levels , could be used as prognostic tool to predict trail - sensitivity or trail - resistance in the treatment of nsclcs and hccs . it is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not intended to limit the scope of the current teachings . in this application , the use of the singular includes the plural unless specifically stated otherwise . 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 .” also , the use of “ comprise ”, “ contain ”, and “ include ”, or modifications of those root words , for example but not limited to , “ comprises ”, “ contained ”, and “ including ”, are not intended to be limiting . the term “ and / or ” means that the terms before and after can be taken together or separately . for illustration purposes , but not as a limitation , “ x and / or y ” can mean “ x ” or “ y ” or “ x and y ”. it is understood that an mirna is derived from genomic sequences or a gene . in this respect , the term “ gene ” is used for simplicity to refer to the genomic sequence encoding the precursor mirna for a given mirna . however , embodiments of the invention may involve genomic sequences of a mirna that are involved in its expression , such as a promoter or other regulatory sequences . the term “ mirna ” generally refers to a single - stranded molecule , but in specific embodiments , molecules implemented in the invention will also encompass a region or an additional strand that is partially ( between 10 and 50 % complementary across length of strand ), substantially ( greater than 50 % but less than 100 % complementary across length of strand ) or fully complementary to another region of the same single - stranded molecule or to another nucleic acid . thus , nucleic acids may encompass a molecule that comprises one or more complementary or self - complementary strand ( s ) or “ complement ( s )” of a particular sequence comprising a molecule . for example , precursor mirna may have a self - complementary region , which is up to 100 % complementary mirna probes of the invention can be or be at least 60 , 65 , 70 , 75 , 80 , 85 , 90 , 95 , or 100 % complementary to their target . the term “ combinations thereof ” as used herein refers to all permutations and combinations of the listed items preceding the term . for example , “ a , b , c , or combinations thereof ” is intended to include at least one of : a , b , c , ab , ac , bc , or abc , and if order is important in a particular context , also ba , ca , cb , acb , cba , bca , bac , or cab . unless otherwise noted , technical terms are used according to conventional usage . definitions of common terms in molecular biology may be found in benjamin lewin , genes v , published by oxford university press , 1994 ( isbn 0 - 19 - 854287 - 9 ); kendrew et al . ( eds . ), the encyclopedia of molecular biology , published by blackwell science ltd ., 1994 ( isbn 0 - 632 - 02182 - 9 ); and robert a . meyers ( ed . ), molecular biology and biotechnology : a comprehensive desk reference , published by vch publishers , inc ., 1995 ( isbn 1 - 56081 - 569 - 8 ). in order to facilitate review of the various embodiments of the disclosure , the following explanations of specific terms are provided : adjunctive therapy : a treatment used in combination with a primary treatment to improve the effects of the primary treatment . for example , a patient diagnosed with hcc may undergo liver resection as a primary treatment and antisense mir - 221 and mir - 222 therapy as an adjunctive therapy . candidate : as used herein , a “ candidate ” for therapy is a patient that has trail - resistant trail expression pattern . clinical outcome : refers to the health status of a patient following treatment for a disease or disorder , such as hcc , or in the absence of treatment . clinical outcomes include , but are not limited to , an increase in the length of time until death , a decrease in the length of time until death , an increase in the chance of survival , an increase in the risk of death , survival , disease - free survival , chronic disease , metastasis , advanced or aggressive disease , disease recurrence , death , and favorable or poor response to therapy . control : a “ control ” refers to a sample or standard used for comparison with an experimental sample , such as a tumor sample obtained from a patient having trail - resistant cancer . in some embodiments , the control is a liver sample obtained from a healthy patient or a non - cancerous tissue sample obtained from a patient diagnosed with hcc . in some embodiments , the control is a historical control or standard value ( i . e . a previously tested control sample or group of samples that represent baseline or normal values , such as the level trail expression pattern in non - cancerous tissue ). cytokines : proteins produced by a wide variety of hematopoietic and non - hematopoietic cells that affect the behavior of other cells . cytokines are important for both the innate and adaptive immune responses . decrease in survival : as used herein , “ decrease in survival ” refers to a decrease in the length of time before death of a patient , or an increase in the risk of death for the patient . detecting level of expression : for example , “ detecting the level of mir - 221 and mir - 222 expression ” refers to quantifying the amount of mir - 221 and mir - 222 present in a sample . detecting expression of mir - 221 and mir - 222 , or any microrna , can be achieved using any method known in the art or described herein , such as by qrt - pcr . detecting expression of mir - 221 and mir - 222 includes detecting expression of either a mature form of mir - 221 and mir - 222 or a precursor form that is correlated with mir - 221 and mir - 222 expression . typically , mirna detection methods involve sequence specific detection , such as by rt - pcr . mir - 221 and mir - 222 - specific primers and probes can be designed using the precursor and mature mir - 221 and mir - 222 nucleic acid sequences , which are known in the art and include modifications which do not change the function of the sequences . hepatocellular carcinoma ( hcc ): hcc is a primary malignancy of the liver typically occurring in patients with inflammatory livers resulting from viral hepatitis , liver toxins or hepatic cirrhosis ( often caused by alcoholism ). micrornas are generally 21 - 23 nucleotides in length . micrornas are processed from primary transcripts known as pri - mirna to short stem - loop structures called precursor ( pre )- mirna and finally to functional , mature microrna . mature microrna molecules are partially complementary to one or more messenger rna molecules , and their primary function is to down - regulate gene expression . micrornas regulate gene expression through the rnai pathway . mir - 221 and mir - 222 expression : as used herein , “ low mir - 221 and mir - 222 expression ” and “ high mir - mir - 221 and mir - 222 expression ” are relative terms that refer to the level of mir - 221 and mir - 222 found in a sample , such as a healthy or hcc liver sample . in some embodiments , low and high mir - 221 and mir - 222 expression are determined by comparison of mir - 221 and mir - 222 levels in a group of non - cancerous and hcc liver samples . low and high expression can then be assigned to each sample based on whether the expression of mir - 221 and mir - 222 in a sample is above ( high ) or below ( low ) the average or median mir - 221 and mir - 222 expression level . for individual samples , high or low mir - 221 and mir - 222 expression can be determined by comparison of the sample to a control or reference sample known to have high or low expression , or by comparison to a standard value . low and high mir - 221 and mir - 222 expression can include expression of either the precursor or mature forms or mir - 221 and mir - 222 , or both . patient : as used herein , the term “ patient ” includes human and non - human animals . the preferred patient for treatment is a human . “ patient ” and “ subject ” are used interchangeably herein . pharmaceutically acceptable vehicles : the pharmaceutically acceptable carriers ( vehicles ) useful in this disclosure are conventional . remington &# 39 ; s pharmaceutical sciences , by e . w . martin , mack publishing co ., easton , pa ., 15th edition ( 1975 ), describes compositions and formulations suitable for pharmaceutical delivery of one or more therapeutic compounds , molecules or agents . in general , the nature of the carrier will depend on the particular mode of administration being employed . for instance , parenteral formulations usually comprise injectable fluids that include pharmaceutically and physiologically acceptable fluids such as water , physiological saline , balanced salt solutions , aqueous dextrose , glycerol or the like as a vehicle . for solid compositions ( for example , powder , pill , tablet , or capsule forms ), conventional non - toxic solid carriers can include , for example , pharmaceutical grades of mannitol , lactose , starch , or magnesium stearate . in addition to biologically - neutral carriers , pharmaceutical compositions to be administered can contain minor amounts of non - toxic auxiliary substances , such as wetting or emulsifying agents , preservatives , and ph buffering agents and the like , for example sodium acetate or sorbitan monolaurate . preventing , treating or ameliorating a disease : “ preventing ” a disease ( such as hcc ) refers to inhibiting the full development of a disease . “ treating ” refers to a therapeutic intervention that ameliorates a sign or symptom of a disease or pathological condition after it has begun to develop . “ ameliorating ” refers to the reduction in the number or severity of signs or symptoms of a disease . screening : as used herein , “ screening ” refers to the process used to evaluate and identify candidate agents that affect trail expression patterns . in some cases , screening involves contacting a candidate agent ( such as an antibody , small molecule or cytokine ) with trail - resistant cancer cells and testing the effect of the agent on trail expression patterns . expression of a microrna can be quantified using any one of a number of techniques known in the art and described herein , such as by microarray analysis or by qrt - pcr . small molecule : a molecule , typically with a molecular weight less than about 1000 daltons , or in some embodiments , less than about 500 daltons , wherein the molecule is capable of modulating , to some measurable extent , an activity of a target molecule . therapeutic agent : a chemical compound , small molecule , or other composition , such as an antisense compound , antibody , protease inhibitor , hormone , chemokine or cytokine , capable of inducing a desired therapeutic or prophylactic effect when properly administered to a subject . for example , therapeutic agents for trail - resistant cancer cells include agents that prevent or inhibit development or metastasis of trail - resistant cancer cells . as used herein , a “ candidate agent ” is a compound selected for screening to determine if it can function as a therapeutic agent for trail - resistant cancer cells . in some embodiments , the candidate agent is identified as a therapeutic agent if the agent converts the cell from in trail - resistant cancer cells . “ incubating ” includes a sufficient amount of time for an agent to interact with a cell or tissue . “ contacting ” includes incubating an agent in solid or in liquid form with a cell or tissue . “ treating ” a cell or tissue with an agent includes contacting or incubating the agent with the cell or tissue . therapeutically effective amount : a quantity of a specified pharmaceutical or therapeutic agent sufficient to achieve a desired effect in a subject , or in a cell , being treated with the agent . for example , this can be the amount of a therapeutic agent that decreases expression of mir - 221 and mir - 222 and c - jun or decreases the expression of mir - 221 and mir - 222 in conjunction with increasing pten and / or timp3 thereby prevents , treats or ameliorates trail - resistant cancer cells in a patient . the effective amount of the agent will be dependent on several factors , including , but not limited to the subject or cells being treated , and the manner of administration of the therapeutic composition . trail expression pattern : the comparative expression levels of four genes in a cell , cell culture , or tissue sample , including c - jun , mir - 221 and mir - 222 , pten and timp3 . trail - resistant trail expression pattern : is a trail expression pattern wherein c - jun and mir - 221 and mir - 222 expression is high , and pten and timp3 expression is low compared to control . trail resistant cancer cells , trail resistant cancer , trail resistant tumor cells or tumor , and the like : cells ( in vitro , in situ , in vivo ) which , if challenged with trail , no or little apoptosis in response to trail would be observed compared to control . this definition does not require trail challenge testing of every putative trail resistant cell in order to meet the definition ; rather , sampling , staining , phenotypic or genetic marker identification , known trail status , or any other suggestion of trail resistance , is within the meaning of this definition . trail - sensitive trail expression pattern : is a trail expression pattern wherein c - jun and mir - 221 and mir - 222 expression is low , and pten and timp3 expression is high compared to control . tumor , neoplasia , malignancy or cancer : the result of abnormal and uncontrolled growth of cells . neoplasia , malignancy , cancer and tumor are often used interchangeably and refer to abnormal growth of a tissue or cells that results from excessive cell division . the amount of a tumor in an individual is the “ tumor burden ” which can be measured as the number , volume , or weight of the tumor . a tumor that does not metastasize is referred to as “ benign .” a tumor that invades the surrounding tissue and / or can metastasize is referred to as “ malignant .” tumor - node - metastasis ( tnm ): the tnm classification of malignant tumors is a cancer staging system for describing the extent of cancer in a patient &# 39 ; s body . t describes the size of the primary tumor and whether it has invaded nearby tissue ; n describes any lymph nodes that are involved ; and m describes metastasis . tnm is developed and maintained by the international union against cancer to achieve consensus on one globally recognized standard for classifying the extent of spread of cancer . the tnm classification is also used by the american joint committee on cancer and the international federation of gynecology and obstetrics . in some embodiments , the control is non - cancerous tissue sample obtained from the same patient . in other embodiments , the control is a liver sample obtained from a healthy subject , such as a healthy liver donor . in another example , the control is a standard calculated from historical values . tumor samples and non - cancerous tissue samples can be obtained according to any method known in the art . for example , tumor and non - cancerous samples can be obtained from hcc patients that have undergone liver resection , or they can be obtained by extraction using a hypodermic needle , by microdissection , or by laser capture . control ( non - cancerous ) samples can be obtained , for example , from a cadaveric donor or from a healthy liver donor . in some embodiments , screening comprises contacting the candidate agents with cells . the cells can be primary cells obtained from a patient , or the cells can be immortalized or transformed cells . the candidate agents can be any type of agent , such as a protein , peptide , small molecule , antibody or nucleic acid . in some embodiments , the candidate agent is a cytokine . in some embodiments , the candidate agent is a small molecule . screening includes both high - throughout screening and screening individual or small groups of candidate agents . the sequences of precursor micrornas ( pre - mirnas ) and mature mirnas are publicly available , such as through the mirbase database , available online by the sanger institute ( see griffiths - jones et al ., nucleic acids res . 36 : d154 - d158 , 2008 ; griffiths - jones et al ., nucleic acids res . 34 : d140 - d144 , 2006 ; and griffiths - jones , nucleic acids res . 32 : d109 - d111 , 2004 ). detection and quantification of rna expression can be achieved by any one of a number of methods well known in the art ( see , for example , u . s . patent application publication nos . 2006 / 0211000 and 2007 / 0299030 , herein incorporated by reference ) and described below . using the known sequences for rna family members , specific probes and primers can be designed for use in the detection methods described below as appropriate . in some cases , the rna detection method requires isolation of nucleic acid from a sample , such as a cell or tissue sample . nucleic acids , including rna and specifically mirna , can be isolated using any suitable technique known in the art . for example , phenol - based extraction is a common method for isolation of rna . phenol - based reagents contain a combination of denaturants and rnase inhibitors for cell and tissue disruption and subsequent separation of rna from contaminants . phenol - based isolation procedures can recover rna species in the 10 - 200 - nucleotide range ( e . g ., precursor and mature mirnas , 5s and 5 . 8s ribosomal rna ( rrna ), and ui small nuclear rna ( snrna )). in addition , extraction procedures such as those using trizol ™ or trireagent ™, will purify all rnas , large and small , and are efficient methods for isolating total rna from biological samples that contain mirnas and small interfering rnas ( sirnas ). a microarray is a microscopic , ordered array of nucleic acids , proteins , small molecules , cells or other substances that enables parallel analysis of complex biochemical samples . a dna microarray consists of different nucleic acid probes , known as capture probes that are chemically attached to a solid substrate , which can be a microchip , a glass slide or a microsphere - sized bead . microarrays can be used , for example , to measure the expression levels of large numbers of messenger rnas ( mrnas ) and / or mirnas simultaneously . microarrays can be fabricated using a variety of technologies , including printing with fine - pointed pins onto glass slides , photolithography using pre - made masks , photolithography using dynamic micromirror devices , ink - jet printing , or electrochemistry on microelectrode arrays . microarray analysis of mirnas , for example ( although these procedures can be used in modified form for any rna analysis ) can be accomplished according to any method known in the art ( see , for example , pct publication no . wo 2008 / 054828 ; ye et al ., nat . med . 9 ( 4 ): 416 - 423 , 2003 ; calin et al ., n . engl . j . med . 353 ( 17 ): 1793 - 1801 , 2005 , each of which is herein incorporated by reference ). in one example , rna is extracted from a cell or tissue sample , the small rnas ( 18 - 26 - nucleotide rnas ) are size - selected from total rna using denaturing polyacrylamide gel electrophoresis . oligonucleotide linkers are attached to the 5 ′ and 3 ′ ends of the small rnas and the resulting ligation products are used as templates for an rt - pcr reaction with 10 cycles of amplification . the sense strand pcr primer has a fluorophore attached to its 5 ′ end , thereby fluorescently labeling the sense strand of the pcr product . the pcr product is denatured and then hybridized to the microarray . a pcr product , referred to as the target nucleic acid that is complementary to the corresponding mirna capture probe sequence on the array will hybridize , via base pairing , to the spot at which the capture probes are affixed . the spot will then fluoresce when excited using a microarray laser scanner . the fluorescence intensity of each spot is then evaluated in terms of the number of copies of a particular mirna , using a number of positive and negative controls and array data normalization methods , which will result in assessment of the level of expression of a particular mirna . in an alternative method , total rna containing the small rna fraction ( including the mirna ) extracted from a cell or tissue sample is used directly without size - selection of small rnas , and 3 ′ end labeled using t4 rna ligase and either a fluorescently - labeled short rna linker the rna samples are labeled by incubation at 30 ° c . for 2 hours followed by heat inactivation of the t4 rna ligase at 80 ° c . for 5 minutes . the fluorophore - labeled mirnas complementary to the corresponding mirna capture probe sequences on the array will hybridize , via base pairing , to the spot at which the capture probes are affixed . the microarray scanning and data processing is carried out as described above . there are several types of microarrays than be employed , including spotted oligonucleotide microarrays , pre - fabricated oligonucleotide microarrays and spotted long oligonucleotide arrays . in spotted oligonucleotide microarrays , the capture probes are oligonucleotides complementary to mirna sequences . this type of array is typically hybridized with amplified pcr products of size - selected small rnas from two samples to be compared ( such as non - cancerous tissue and hcc liver tissue ) that are labeled with two different fluorophores . alternatively , total rna containing the small rna fraction ( including the mirnas ) is extracted from the two samples and used directly without size - selection of small rnas , and 3 ′ end labeled using t4 rna ligase and short rna linkers labeled with two different fluorophores . the samples can be mixed and hybridized to one single microarray that is then scanned , allowing the visualization of up - regulated and down - regulated mirna genes in one assay . in pre - fabricated oligonucleotide microarrays or single - channel microarrays , the probes are designed to match the sequences of known or predicted mirnas . there are commercially available designs that cover complete genomes ( for example , from affymetrix or agilent ). these microarrays give estimations of the absolute value of gene expression and therefore the comparison of two conditions requires the use of two separate microarrays . spotted long oligonucleotide arrays are composed of 50 to 70 - mer oligonucleotide capture probes , and are produced by either ink jet or robotic printing . short oligonucleotide arrays are composed of 20 - 25 - mer oligonucleotide probes , and are produced by photolithographic synthesis ( affymetrix ) or by robotic printing . quantitative rt - pcr ( qrt - pcr ) is a modification of polymerase chain reaction used to rapidly measure the quantity of a product of polymerase chain reaction . qrt - pcr is commonly used for the purpose of determining whether a genetic sequence , such as a mir , is present in a sample , and if it is present , the number of copies in the sample . any method of pcr that can determine the expression of a nucleic acid molecule , including a mirna , falls within the scope of the present disclosure . there are several variations of the qrt - pcr method known in the art , three of which are described below . methods for quantitative polymerase chain reaction include , but are not limited to , via agarose gel electrophoresis , the use of sybr green ( a double stranded dna dye ), and the use of a fluorescent reporter probe . the latter two can be analyzed in real - time . with agarose gel electrophoresis , the unknown sample and a known sample are prepared with a known concentration of a similarly sized section of target dna for amplification . both reactions are run for the same length of time in identical conditions ( preferably using the same primers , or at least primers of similar annealing temperatures ). agarose gel electrophoresis is used to separate the products of the reaction from their original dna and spare primers . the relative quantities of the known and unknown samples are measured to determine the quantity of the unknown . the use of sybr green dye is more accurate than the agarose gel method , and can give results in real time . a dna binding dye binds all newly synthesized double stranded dna and an increase in fluorescence intensity is measured , thus allowing initial concentrations to be determined however , sybr green will label all double - stranded dna , including any unexpected pcr products as well as primer dimers , leading to potential complications and artifacts . the reaction is prepared as usual , with the addition of fluorescent double - stranded dna dye . the reaction is run , and the levels of fluorescence are monitored ( the dye only fluoresces when bound to the double - stranded dna ). with reference to a standard sample or a standard curve , the double - stranded dna concentration in the pcr can be determined the fluorescent reporter probe method uses a sequence - specific nucleic acid based probe so as to only quantify the probe sequence and not all double stranded dna . it is commonly carried out with dna based probes with a fluorescent reporter and a quencher held in adjacent positions ( so - called dual - labeled probes ). the close proximity of the reporter to the quencher prevents its fluorescence ; it is only on the breakdown of the probe that the fluorescence is detected . this process depends on the 5 ′ to 3 ′ exonuclease activity of the polymerase involved . the real - time quantitative pcr reaction is prepared with the addition of the dual - labeled probe . on denaturation of the double - stranded dna template , the probe is able to bind to its complementary sequence in the region of interest of the template dna . when the pcr reaction mixture is heated to activate the polymerase , the polymerase starts synthesizing the complementary strand to the primed single stranded template dna . as the polymerization continues , it reaches the probe bound to its complementary sequence , which is then hydrolyzed due to the 5 ′- 3 ′ exonuclease activity of the polymerase , thereby separating the fluorescent reporter and the quencher molecules . this results in an increase in fluorescence , which is detected . during thermal cycling of the real - time pcr reaction , the increase in fluorescence , as released from the hydrolyzed dual - labeled probe in each pcr cycle is monitored , which allows accurate determination of the final , and so initial , quantities of dna . in situ hybridization ( ish ) applies and extrapolates the technology of nucleic acid hybridization to the single cell level , and , in combination with the art of cytochemistry , immunocytochemistry and immunohistochemistry , permits the maintenance of morphology and the identification of cellular markers to be maintained and identified , and allows the localization of sequences to specific cells within populations , such as tissues and blood samples . ish is a type of hybridization that uses a complementary nucleic acid to localize one or more specific nucleic acid sequences in a portion or section of tissue ( in situ ), or , if the tissue is small enough , in the entire tissue ( whole mount ish ). rna ish can be used to assay expression patterns in a tissue , such as the expression of mirnas . sample cells or tissues are treated to increase their permeability to allow a probe , such as a mirna - specific probe , to enter the cells . the probe is added to the treated cells , allowed to hybridize at pertinent temperature , and excess probe is washed away . a complementary probe is labeled with a radioactive , fluorescent or antigenic tag , so that the probe &# 39 ; s location and quantity in the tissue can be determined using autoradiography , fluorescence microscopy or immunoassay . the sample may be any sample as herein described , such as a non - cancerous or hcc liver sample . since the sequences of mir - 26 family members are known , mir - 26 probes can be designed accordingly such that the probes specifically bind mir - 26 . in situ pcr is the pcr based amplification of the target nucleic acid sequences prior to ish . for detection of rna , an intracellular reverse transcription step is introduced to generate complementary dna from rna templates prior to in situ pcr . this enables detection of low copy rna sequences . prior to in situ pcr , cells or tissue samples are fixed and permeabilized to preserve morphology and permit access of the pcr reagents to the intracellular sequences to be amplified . pcr amplification of target sequences is next performed either in intact cells held in suspension or directly in cytocentrifuge preparations or tissue sections on glass slides . in the former approach , fixed cells suspended in the pcr reaction mixture are thermally cycled using conventional thermal cyclers . after pcr , the cells are cytocentrifuged onto glass slides with visualization of intracellular pcr products by ish or immunohistochemistry . in situ pcr on glass slides is performed by overlaying the samples with the pcr mixture under a coverslip which is then sealed to prevent evaporation of the reaction mixture . thermal cycling is achieved by placing the glass slides either directly on top of the heating block of a conventional or specially designed thermal cycler or by using thermal cycling ovens . detection of intracellular pcr products is generally achieved by one of two different techniques , indirect in situ pcr by ish with pcr - product specific probes , or direct in situ pcr without ish through direct detection of labeled nucleotides ( such as digoxigenin - 11 - dutp , fluorescein - dutp , 3h - ctp or biotin - 16 - dutp ), which have been incorporated into the pcr products during thermal cycling . use of mir - 221 and mir - 222 and c - jun , pten and timp3 as predictive markers of prognosis and for identification of therapeutic agents for treatment of trail resistant cancer cells it is disclosed herein that expression patterns of mir - 221 and mir - 222 , c - jun , pten and timp3 are predictors of survival prognosis in trail - resistant patients . trail resistant cancer cells samples ( for example , tissue biopsy samples ) with high mir - 221 and mir - 222 and c - jun expression , along with low pten and timp3 expression compared to non - cancerous tissue from the same subject or from a healthy subject , predicts a decrease in survival . thus , the trail resistant expression pattern status in tumors can be used as a clinical tool in trail - resistant cancer patients &# 39 ; prognosis . in some embodiments , the expression level of the markers herein in a trail - resistant tumor sample is directly compared with the trail resistant expression pattern in surrounding non - cancerous tissue from the same patient . in other embodiments , trail resistant expression pattern in the tumor sample is compared to the trail resistant expression pattern in a liver sample obtained from a healthy subject , such as a liver donor . in some cases , the non - cancerous tissue used as a control sample is obtained from a cadaver . in other embodiments , the trail resistant expression pattern in the tumor sample is compared with a standard level based on historical values . for example , the standard can be set based on average trail resistant expression pattern in non - cancerous liver tissue samples obtained from a cohort of subjects . for instance , the cohort of subjects can be a group of hcc patients enrolled in a clinical trial . the cohort of subject can also be a group of cadaveric donors . finding a trail resistant expression pattern in a hcc tumor sample relative to a control indicates a poor prognosis for the patient and identifies the patient as a good candidate for specialized therapy . as used herein , “ poor prognosis ” generally refers to a decrease in survival , or in other words , an increase in risk of death or a decrease in the time until death . poor prognosis can also refer to an increase in severity of the disease , such as an increase in spread ( metastasis ) of the cancer to other organs . in one embodiment , trail resistant expression pattern is found when the respective markers show at least a 1 . 5 - fold increase or decrease in expression relative to the control . in other embodiments , trail resistant expression pattern is indicated by at least a 2 - fold , at least a 2 . 5 - fold , at least a 3 - fold , at least a 3 . 5 - fold , or at least a 4 - fold increase or decrease in the markers of trail resistant expression pattern relative to the control . the finding that patients with trail resistant tumors having a trail sensitive expression pattern have a better chance of survival indicates that compounds that decrease c - jun , mir - 221 and mir - 222 expression in conjunction with increasing pten and timp3 expression will be useful as therapeutic agents for the treatment of trail resistant tumors . thus , provided herein is a method of identifying therapeutic agents for the treatment of trail resistant cancer cells , comprising screening candidate agents in vitro to select an agent that promote conversion from trail resistant trail expression pattern to trail sensitive trail expression pattern . in some embodiments , screening comprises contacting the candidate agents with trail resistant cancer cells and detecting any change trail expression pattern . the trail resistant cancer cells can be primary cells obtained from a patient , immortalized or transformed cells obtained from a patient , or the cells can be commercially available immortalized cell lines , such as , but not limited to mhcc97 , hepg2 , hep3b or snu - 423 cells . a conversion to trail sensitive expression pattern following treatment with the candidate agent identifies the agent as a therapeutic agent for the treatment of trail resistant cancer . methods of screening candidate agents to identify therapeutic agents for the treatment of disease are well known in the art . methods of detecting expression levels of rna and proteins are known in the art and are described herein , such as , but not limited to , microarray analysis , rt - pcr ( including qrt - pcr ), in situ hybridization , in situ pcr , and northern blot analysis . in one embodiment , screening comprises a high - throughput screen . in another embodiment , candidate agents are screened individually . the candidate agents can be any type of molecule , such as , but not limited to nucleic acid molecules , proteins , peptides , antibodies , lipids , small molecules , chemicals , cytokines , chemokines , hormones , or any other type of molecule that may alter trail expression pattern ( s ) either directly or indirectly . in some embodiments , the candidate agents are molecules that play a role in the nfκb / il - 6 signaling pathway . in other embodiments , the candidate agents are molecules that play a role in the il - 10 , stat3 or interferon - inducible factor signaling networks . in one embodiment , the candidate agents are cytokines . in another embodiment , the candidate agents are small molecules . also described herein is a method for the characterization of trail resistant cancer , wherein at least one feature of trail resistant cancer is selected from one or more of the group consisting of : presence or absence of trail resistant cancer ; diagnosis of trail resistant cancer ; prognosis of trail resistant cancer ; therapy outcome prediction ; therapy outcome monitoring ; suitability of trail resistant cancer to treatment , such as suitability of trail resistant cancer to chemotherapy treatment and / or radiotherapy treatment ; suitability of trail resistant cancer to hormone treatment ; suitability of trail resistant cancer for removal by invasive surgery ; suitability of trail resistant cancer to combined adjuvant therapy . also described herein is a kit for the detection of trail resistant cancer , the kit comprising at least one detection probe comprising c - jun and mir - 221 and mir - 222 or mir - 221 and mir - 222 and pten and / or timp3 . the kit can be in the form or comprises an oligonucleotide array . also described herein is a method for the determination of suitability of a trail resistant cancer patient for treatment comprising : i ) isolating at least one tissue sample from a patient suffering from trail resistant cancer ; ii ) performing the characterization of at least one tissue sample and / or utilizing a detection probe , to identify the trail expression pattern ; iii ) based on the at least one feature identified in step ii ), diagnosing the physiological status of the patient ; iv ) based on the diagnosis obtained in step iii ), determining whether the patient would benefit from treatment of the trail resistant cancer . in certain embodiments , the at least one feature of the cancer is selected from one or more of the group consisting of : presence or absence of the cancer ; type of the cancer ; origin of the cancer ; diagnosis of cancer ; prognosis of the cancer ; therapy outcome prediction ; therapy outcome monitoring ; suitability of the cancer to treatment , such as suitability of the cancer to chemotherapy treatment and / or radiotherapy treatment ; suitability of the cancer to hormone treatment ; suitability of the cancer for removal by invasive surgery ; suitability of the cancer to combined adjuvant therapy . also described herein is a method of for the determination of suitability of a cancer for treatment , wherein the at least one feature of the cancer is suitability of the cancer to treatment , such as suitability of the cancer to chemotherapy treatment and / or radiotherapy treatment ; suitability of the cancer to hormone treatment ; suitability of the cancer for removal by invasive surgery ; suitability of the cancer to combined adjuvant therapy . also described herein is a method for the determination of the likely prognosis of a cancer patient comprising : i ) isolating at least one tissue sample from a patient suffering from cancer ; and , ii ) characterizing at least one tissue sample to identify the trail expression pattern ; wherein the feature allows for the determination of the likely prognosis of the cancer patient . the following examples are provided to illustrate certain particular features and / or embodiments . these examples should not be construed to limit the disclosure to the particular features or embodiments described . to identify putative mir - 221 and mir - 222 targets , a bioinformatics search ( targetscan , pictar , rnhybrid ) was conducted . among the candidate targets , 3 ′- utrs of human pten ( nucleotides 200 - 207 , nm — 000314 ) and human timp3 ( nucleotides 2443 - 2449 , nm — 000362 ) contained regions that matched the seed sequences of hsa - mir - 221 and mir - 222 ( fig1 a ). to ascertain whether pten and timp3 are direct targets of mir - 221 and mir - 222 , pten and timp3 3 ′ utr containing the mir - 221 / mir - 222 binding sites were cloned downstream of the luciferase open reading frame . these reporter constructs were used to transfect meg01 cells , which express very low levels of mir - 221 and mir - 222 ( fig1 b ) and are highly transfectable ( freson et al ., 2005 ). increased expression of these mirs upon transfection , confirmed by qrt - pcr ( fig1 b ), significantly affected luciferase expression , measured as relative luciferase activity ( fig1 c ). conversely , when luciferase assays were performed by using a plasmid harboring the 3 ′ utr of pten and timp3 mrnas , where the binding sites for mir - 221 and mir - 222 were inactivated by site - directed mutagenesis , there was observed a consistent reduction in mir - 221 and mir - 222 inhibitory effect ( fig1 c ). to determine if these micrornas affect pten and timp3 expression in the h460 cellular environment , the consequences of the ectopic expression of mir - 221 and mir - 222 in h460 cells were analyzed . increased expression of these mirs upon transfection was confirmed by qrt - pcr ( fig1 d ) and then the effects on endogenous levels of pten and timp3 were analyzed by western blot ( fig1 e ); mir - 221 and mir - 222 over - expression significantly reduced the endogenous levels of pten and timp3 , compared to h460 cells transfected with scrambled pre - mir . conversely , knockdown of mir - 221 and mir - 222 by 2 ′- o - me - anti - mir - 221 and 2 ′- o - me - anti - mir - 222 , confirmed by qrt - pcr ( fig1 f ) in calu - 1 - lung derived cells with high levels of endogenous mir - 221 and mir - 222 , increased the protein levels of pten and timp3 ( fig1 g ). intriguingly , by quantitative rt - pcr , it was found that pten , but not timp3 mrna levels , were strongly reduced in the mir - 221 and mir - 222 transfected cells ( fig1 h ), indicating that mir - 221 and mir - 222 induce the degradation of pten mrna while timp3 is regulated by these micrornas only at the translational level . pten and timp3 3 ′ utrs are therefore direct targets of mir - 221 and mir - 222 . mir - 221 and mir - 222 are inversely correlated with pten and timp3 expression in nsclc and hcc the endogenous levels of mir - 221 and mir - 222 were evaluated by northern blot in large panels of primary nsclcs and hccs , compared with the normal counterpart . mir - 221 and mir - 222 expression was almost undetectable in normal lung and liver cells but highly expressed in the majority of tumor cell lines . moreover , as assessed by western blot , an inverse correlation between mir - 221 and mir - 222 rna expression and pten and timp3 protein expression was found in most cell lines analyzed ( fig2 a ), confirmed also by qrt - pcr ( fig2 b ). timp3 mrna expression levels was not tested because down - regulation of timp3 mrna after enforced mir - 221 and mir - 222 expression was not observed ( fig1 h ). these results indicate that high expression of mir - 221 and mir - 222 is one of the mechanisms acting to negatively regulate pten and timp3 in nsclc and hcc . to verify whether these micrornas affected pten and timp3 endogenous levels also in hcc , analysis of the effects of the ectopic expression of mir - 221 and mir - 222 in the sk - hep1 cell line , which expresses low levels of mir - 221 and mir - 222 , was performed . as shown in fig3 a , pten and timp3 proteins were reduced in sk - hep1 cells upon mir - 221 and mir - 222 over - expression . conversely , knockdown of mir - 221 and mir - 222 by 2 ′- o - me - anti - mir - 221 and 2 ′- o - me - anti - mir - 222 in snu - 387 cells , which expressed high levels of endogenous mir - 221 and mir - 222 , increased the protein level of pten and timp3 ( fig3 a ). having noted that mir - 221 and mir - 222 down - regulate pten and timp3 expression in both nsclc and hcc - derived cells in culture , regulation in vivo was studied . to answer this question , pten mrna and mir - 221 and mir - 222 expression by qrt - pcr in primary lung tumor specimens was studied , in comparison with normal human lung tissue samples . mir - 221 and mir - 222 were almost undetectable in normal human lung samples and highly expressed in all the tumor samples analyzed . of the 22 primary lung tumors examined , in fact , all exhibited down - regulation of pten and over - expression of mir - 221 and mir - 222 ( fig3 b ). these data further support the finding that pten is a direct target of mir - 221 and mir - 222 also in vivo . to corroborate these findings , in situ hybridization analysis was performed , by using 5 ′- dig - labeled lna probes , on hepatocarcinoma and normal liver tissues , followed by immunohistochemistry for pten and timp3 ( fig3 c ). mir - 221 / mir - 222 and pten / timp3 expressions were inversely related in liver cancers and the adjacent normal / cirrhotic liver tissues . liver cancer cells showed high expression of mir - 221 / mir - 222 and rarely expressed pten or timp3 ( fig3 cg - h - k - l ) whereas the adjacent non - malignant liver expressed pten and timp3 abundantly and rarely showed detectable mir - 221 / mir - 222 signal ( fig3 ca - b - e - f ). mir - 221 / mir - 222 and pten / timp3 expression were also inversely related in lung cancers and the adjacent normal lung tissues ( fig9 ). the majority of cancer cells were positive for mir - 221 and mir - 222 and negative for pten ( fig9 f - 9g ) and timp3 ( fig9 i - 9j ). in fig9 i - 9j mirna expression was evident in the cancer cells and timp3 expression in the surrounding cells . a strong mir - 222 signal ( large arrow ) was found in the nests of tumor cells that are infiltrating the adjacent fibrotic lung tissue ( fig9 k - 9l ). mir - 221 and mir - 222 induce trail resistance in nsclc and hcc by targeting pten and timp3 the effects of mir - 221 and mir - 222 and / or pten - timp3 silencing on cell survival and trail resistance in both nsclc and hcc were studied . first there was performed a proliferation assay on 5 hcc - derived cell lines , three of them ( hepg2 , sk - hep1 and huh 7 ) with low mir - 221 - mir - 222 expression and two ( plc / prf - 5 and snu - 387 ) with high mir - 221 - mir - 222 expression level ( fig4 a ). cells were exposed to trail for 24 hours and subsequently cell proliferation was assessed using an mtt assay . interestingly , cells expressing low levels of mir - 221 and mir - 222 underwent trail - induced cell death , showing a very low proliferation rate , whereas cells over - expressing mir - 221 and mir - 222 did not display sensitivity when exposed to soluble trail ( fig4 a ). moreover , annexin - fitc and caspase 3 / 7 assays on trail - sensitive cell lines sk - hep1 cells , ( fig4 b - 4c ), hepg2 and huh7 ( fig1 a - 10b ), revealed an increase of about 30 - 40 % in trail resistance after mir - 221 and mir - 222 over - expression , as well as after pten and timp3 silencing by pten and timp3 sirnas . trail - sensitive h460 cells also became more resistant to trail inducing - apoptosis after pten and timp3 knockdown , as determined by caspase 3 / 7 activity ( fig4 d ) and annexin - fitc assay ( fig4 e ), although pten silencing was more effective than timp3 . moreover , to further evaluate the contribution of these targets on trail - inducing apoptosis , pten and timp3 sequences were cloned in pcruz - ha plasmid ( santa cruz ) and used to transfect calu - 1 trail - resistant cells . calu - 1 cells became more sensitive to trail inducing - apoptosis after pten and timp3 restoration , alone or in combination , as determined by caspase 3 / 7 activity ( fig4 d ) and annexin - fitc staining ( fig1 a - 11b ). to further investigate the role of timp3 in trail - inducing apoptosis the expression of caspase - 3 ,- 8 - 9 , poly - adp - ribose polymerase ( parp ) and some of the molecule involved in the trail - signaling pathway were tested by western blot after timp3 overexpression in calu - 1 cell line ( fig1 c ). interestingly , the activation of parp and the caspase cascade were observed , as assessed by the appearance of the cleaved fragments . moreover , mc1 - 1 expression was down - regulated while cytochrome c expression increased ( fig1 c ). all together these results suggest an involvement of timp3 in both the extrinsic and intrinsic apoptotic pathways and highlight its role in trail - inducing apoptosis . the same results were obtained after timp3 restoration in snu - 387 cells ( data not shown ). further , the expression and / or the activation of some of the proteins involved in the pi3k / akt pathway after mir - 221 and mir - 222 enforced expression in h460 cells or after mir - 221 / mir - 222 silencing in snu - 387 cells was conducted . as shown in fig5 a , the expression levels of pi3k , akt and its phosphorylated substrate , phospho - glycogen synthase kinase 3 , were elevated by ectopic expression of mir - 221 and mir - 222 , and , in contrast , were decreased by knockdown of mir - 221 and mir - 222 in snu - 387 cells , indicating that mir - 221 and mir - 222 target the pten / akt pathway ( fig5 b ). further investigation of the activation and expression levels of these proteins was conducted . there was found an increase in erks phosphorylation and pak1 expression , as compared with h460 cells transfected with the control mir ( fig5 c ). interestingly , increased expression of metallopeptidase 3 and metallopeptidase 9 was also found , as possible result of timp3 down - regulation ( fig5 a - 5c ). to test if the activation of the previous proteins was pten and / or timp3 - dependent , pten and timp3 were silenced in h460 cells . as shown in fig5 d and e the activation of the erks and pak1 is both pten and timp3 - dependent , while akt phosphorylation is pten - dependent and mmp3 and mmp9 are upregulated after timp3 knockdown . finally , akt inhibition was studied , as it relates to whether it could override mir - 221 and mir - 222 - induced cell survival and trail - resistance . calu - 1 and snu - 387 were transfected with 2 ′- o - methyl ( 2 ′- o - me )- anti - mir - 221 and mir - 222 oligoribonucleotides . cells transfected with 2 ′- o - me - scrambled mir were used as control . blocking mir - 221 and mir - 222 expression considerably sensitized these cells to trail - induced apoptosis , as assessed by caspase 3 / 7 assay ( fig5 f - 5g ). moreover , calu - 1 and snu - 387 cells were treated with the specific akt inhibitor , api - 2 / triciribine , with or without trail . as shown in fig5 f and 5g , api - 2 abrogated mir 221 and mir - 222 - activated akt and significantly inhibited mir - 221 and mir - 222 - induced cell survival and trail resistance . next , to directly compare the growth of tumors with and without pten and timp3 , short hairpin rna ( shrna ) constructs , designed to knockdown gene expression , were used to silence pten and timp3 in h460 cells . an shrna plasmid , encoding a scrambled shrna sequence that does not lead to the specific degradation of any known cellular mrna , was used as control . the consequences of pten and timp3 disruption on tumor growth and trail resistance was assessed in vivo by implanting h460 pten and timp3 knockdown cells into the right dorsal sides of nude mice . trail treatment was initiated 5 days afterwards , when lung carcinoma had been established . pten and timp3 loss ( fig1 a ) conferred not only a significant tumor growth advantage but also resistance to trail - inducing apoptosis over control tumors ( fig1 b - 12 c - 12 d - 2 e - 12 f - 12 g ). in conclusion , pten and timp3 are important targets in trail resistance and play an important role in tumorigenicity of nsclc and hcc cells . pten and timp3 down - regulation by mir - 221 and mir - 222 induces migration and invasiveness in nsclc and hcc cells to directly test the functional role of mir - 221 / mir - 222 in tumorigenesis , these two micrornas were over - expressed , or pten and timp3 were silenced , in h460 and sk - hep1 cells . then , by cell cycle analysis , mir - 221 and mir - 222 and pten sirna h460 transfected cells showed a decrease of g1 and a corresponding increase of the s and g2 - m phases ( fig6 a ). after 72 h of transfection the analysis revealed an earlier onset of dna synthesis induced by mir - 221 and mir - 222 or pten knockdown , paralleled by a faster reduction of g1 cells , contributing to the proliferative advantage ( fig6 a ). the same change was observed in sk - hep1 cells ( fig1 a ). next , the inventors analyzed the effects of mir - 221 and mir - 222 over - expression on cellular migration and invasion of nsclc and hcc cells . interestingly , a significant increase on the migratory ( fig6 b - 6c ) and invasive ( fig6 d ) capabilities of h460 and sk - hep1 ( fig1 b ) cells after mir - 221 and mir - 222 overexpression as well after pten and timp3 downregulation was observed . conversely , when mir - 221 and mir - 222 were down - regulated by transfection with 2 ′- o - me - anti - mir - 221 and mir - 222 , a decrease in cell migration and invasion in both calu - 1 and snu - 387 cells ( fig1 a - 14b ) was observed . met was silenced by using sirna , in calu - 1 and snu - 387 cells and in a gastric cell line ( gtl16 ), previously reported to over - express met oncogene due to dna amplification ( giordano et al ., 1989 ). first , mir - 221 and mir - 222 expression levels were evaluated by qrt - pcr . after met knockdown , mir - 221 and mir - 222 expression was down - regulated in all cell lines analyzed ( fig7 a - 7 b - 7 c ). the same result was obtained by treating gtl16 cells with a met inhibitor , su11274 ( fig1 a ). secondly , by immunostaining , there was observed increased pten and timp3 expression levels after met down - regulation or inhibition , indicating that met is involved in mir - 221 and mir - 222 activation ( fig7 d - 7 e - 7 f ). next , by bioinformatics search ( tess database : http :// www . cbil . upenn . edu / cgi - bin / tess / tess ), it was found that the only transcription factor involved in the met pathway predicted to bind and transcriptionally activate mir - 221 / mir - 222 promoter was ap - 1 . ap - 1 is a dimeric basic region - leucine zipper protein that belongs to the jun and fos subfamilies c - jun is the most potent transcriptional activator in its group . to identify which factor belonging to the ap - 1 family was involved in mir - 221 / mir - 222 transcriptional activation , the correlation between mir - 221 and mir - 222 expression and c - jun and c - fos protein levels in 4 different cell lines ( h460 , calu - 1 , huh7 and snu - 387 ) ( figure s 7 b ) was studied . calu - 1 , highly expressing c - jun and c - fos , were co - transfected with met sirna , c - jun sirna or c - fos sirna . subsequent qrt - pcr amplification showed that met and c - jun down - regulation , but not c - fos knockdown , gave rise to a reduction of ˜ 45 - 50 % in mir - 221 and mir - 222 expression levels , as compared with the negative control ( figure s 7 c ). to further confirm these results luciferase assays were conducted . in previous work , the inventors found that mir - 221 and mir - 222 are transcribed into a single species of 2 . 1 kb rna and the transcription is regulated by the upstream sequence located at − 150 bp / 50 bp from the 5 ′ end of mir - 222 hairpin structure . to determine if the previously identified mir - 221 and mir - 222 promoter region was affected by met / ap1 , the luciferase assay was performed by using the reporter plasmids containing the fragments spanning + 3 ˜− 150 , + 3 ˜− 600 , + 3 ˜− 1000 (+ 1 position corresponds to the 5 ′ terminus of mir - 222 hairpin ) ( fig7 g ) into the pgl3basic vector which harbors the promoter - less luciferase gene ( di leva et al ., unpublished data ). the pgl3b , − 150 , − 600 and − 1000 pgl3b were co - transfected with met sirna , c - jun sirna or c - fos sirna into calu - 1 cells ( fig1 d - 15e ). subsequent luciferase assays showed that met and c - jun down - regulation gave rise to a reduction of ˜ 45 % in luciferase activity , as compared to the basal activity determined by transfection with pgl3b empty vector ; the inventors did not observe a reduction of luciferase activity after c - fos sirna transfection ( fig1 d - 15e ). these data indicate that c - jun and not c - fos is the transcription factor involved in the met pathway , responsible for mir - 221 and mir - 222 activation in nsclc and hcc cells . since the promoter region was responsive to c - jun modulation , to verify a direct binding of c - jun on mir - 221 and mir - 222 promoter , a chromatin immunoprecipitation ( chip ) assays was conducted . first , by bioinformatics analysis , it was found that only one ap - 1 putative binding site is located ˜ 130 bp upstream of the premir - 222 - 5 ′ end . taking into account the predicted ap - 1 binding site , a total of 2 chromatin regions were analyzed ( fig7 g ): one spanning the ap - 1 binding site and the second , as negative control , ˜ 1700 nt upstream of the pre - mir - 222 - 5 ′ end , where the inventors did not find any predicted binding site for ap - 1 . the chip assay of c - jun positive calu - 1 and snu - 387 cells showed remarkable ap - 1 binding at chip analyzed region 2 , proximal to the promoter ( fig7 h - 7i ). no chromatin enrichment by c - jun chip was observed in c - jun negative h460 cells , verifying the specificity of the chip assay . finally , huh7 cells , which show low levels of mir - 221 and mir - 222 , were treated with anisomycin , an antibiotic able to activate jnk kinases , and , thus ap - 1 , mir - 221 and mir - 222 and pten - timp3 expression levels were checked . after c - jun activation ( fig7 m ) by anisomycin , mir - 221 and - 222 expression increased ( mir - 221 = 80 %, mir - 222 = 40 %) as confirmed by qrt - pcr ( fig7 l ), while pten and timp3 expression levels were decreased drastically ( fig7 m ). to further prove that jnk is the intermediate signaling factor between c - met and c - jun and that c - jun knockdown leads to increased pten and timp3 expression , c - met and c - jun in calu - 1 cells were studied and the jnk1 / 2 phosphorylation and pten and timp3 expression were analyzed , respectively . as shown in figure s 7 f , met knockdown reduces jnk1 / 2 phosphorylation while c - jun silencing increases pten / timp3 expression as result of mir - 221 and mir - 222 down modulation . to investigate whether there is a direct relation between met and pten / timp3 in vivo , immunohistochemistry analysis was performed on lung and liver cancer and normal samples . the co - labeling met / pten and met / timp3 showed that pten and timp3 are abundantly expressed only in the normal cells , where met is not present , whereas c - met is expressed exclusively in the cancer cells ( fig1 ). these data confirm that met is implicated in mir - 221 and mir - 222 regulation , at least in part through jnk , ap - 1 and in particular c - jun transcription factor . the 3 ′ utr of the human pten and timp3 genes were pcr amplified using the following primers : pten fw 5 ′- tct aga gac tct gat cca gag aat gaa cc - 3 ′ [ seq id no : 1 ] and pten rw 5 ′- tct aga gtt gcc aca agt gca aag ggg tag gat gtg - 3 ′ [ seq id no : 2 ]; timp3 fw 5 ′- tct aga ctg ggc aaa gaa ggg tct ttc gca aag c - 3 ′ [ seq id no : 3 ] and timp3 rw 5 ′ tct aga ttc caa tag gga gga ggc tgg agg agt ctc - 3 ′ [ seq id no : 4 ] and cloned downstream of the renilla luciferase stop codon in pgl3 control vector ( promega ), giving rise to the p3 ′ utr - pten and p3 ′ utr - timp3 plasmids . these constructs were used to generate , by inverse pcr , the p3 ′- utrmut - pten plasmid - primers : fw : 5 ′- gtt gaa aaa agg ttg ggg gcg ggt gtc atg tat ata c - 3 [ seq id no : 5 ]; rw : 5 ′- gta tat aca tga cac ccg ccc cca acc ttt ttt caa c - 3 ′[ seq id no : 6 ]; p3 ′- utrmut - timp3 plasmid - primers : fw : 5 ′- gta taa ttt aaa atc att ggg cgg cgg gag aca ctt ctg tat ttc - 3 ′ [ seq id no : 7 ]; rw : 5 ′- gaa ata cag aag tgt ctc ccg ccg ccc aat gat ttt aaa tta tac - 3 ′ [ seq id no : 8 ]. meg01 cells were cotransfected with 1 μg of p3 ′ utr - pten or p3 ′ utr - timp3 and with p3 ′ utrmut - pten or p3 ′ utr timp3 plasmids and 1 μg of a renilla luciferase expression construct prl - tk ( promega ) by using lipofectamine 2000 ( invitrogen ). cells were harvested 24 h post - transfection and assayed with dual luciferase assay ( promega ) according to the manufacturer &# 39 ; s instructions . three independent experiments were performed in triplicate . a total of 32 snap - frozen normal and malignant lung tissues ( 19 men and 13 women , median age : 70 . 0 , range : 55 - 82 ) and 60 snap - frozen normal and 60 malignant liver tissues were collected at the ohio state university medical center ( columbus , ohio ). other 72 cancer and normal ( 24 ) lung tissues were purchased from us biomax , inc . all human tissues were obtained according to a protocol approved by the ohio state institutional review board . animal studies were performed according to institutional guidelines . nci - h460 cells were stable transfected by using shpten and timp3 plasmids ( santa cruz ); calu - 1 cells were stable transfected with shmet . after the selection in puromycin for 10 days 5 106 ( h460 ) or 7106 ( calu - 1 ) viable cells were injected s . c . into the right flanks of 6 - wk - old male nude mice ( charles riverbreeding laboratories , wilmington , mass .). treatment started five days ( h460 xenograft ) or ten days ( calu - 1 xenograft ) from tumor cell inoculation by daily ip injections of trail / apo2 ( 10 mg / kg / d ) or vehicle ( pbs ) for two cycles of 5 days . tumor size was assessed every five days by a digital caliper . the tumor volumes were determined by measuring the length ( 1 ) and the width ( w ) and calculating the volume ( v = lw2 / 2 ). 35 days after injection , mice were sacrificed and tumors samples were analyzed by western blot for pten , timp3 and met expression . statistical significance between control and treated animals was evaluated by using student &# 39 ; s t test . animal experiments were conducted after approval of the institutional animal care and use committee , ohio state university . student &# 39 ; s t - test and one - way anova analysis was used to determine significance . all error bars represent the standard error of the mean . pearson correlation coefficient was calculated to test the association between mir - 221 / mir - 222 and pten in the classes normal versus tumor . statistical significance for all the tests , assessed by calculating p - value , was & lt ; 0 . 05 . total proteins from nsclc and hcc cells were extracted with radioimmuno - precipitation assay ( ripa ) buffer ( 0 . 15 mm nacl , 0 . 05 mm tris - hcl , ph 7 . 5 , 1 % triton , 0 . 1 % sds , 0 . 1 % sodium deoxycholate and 1 % nonidet p40 ). sample extract ( 50 μg ) was resolved on 7 . 5 - 12 % sds - polyacrylamide gels ( page ) using a mini - gel apparatus ( bio - rad laboratories ) and transferred to hybond - c extra nitrocellulose . membranes were blocked for 1 h with 5 % nonfat dry milk in tris - buffered saline containing 0 . 05 % tween 20 , incubated overnight with primary antibody , washed and incubated with secondary antibody , and visualized by chemiluminescence . the following primary antibodies were used : anti - pten , anti - c - jun , anti - p - c - jun , anti - fos , anti - p - jnk , anti - mmp3 , anti - mc1 - 1 ( santa cruz ), anti - timp3 ( millipore ) anti - pi3k ( bd biosciences ), anti - erks , anti - phospho erks , anti - akt , anti - p - akt , anti - gsk3b , anti - p - gsk3b ( ser9 ), anti - pak1 anti - caspase - 8 ,- 3 and - 9 , anti - parp , anti - cytochrome c ( cell signaling ) and anti - mmp9 , anti - fadd ( abcam ), anti - 1 - actin antibody ( sigma ). a secondary anti - rabbit or anti - mouse immunoglobulin g ( igg ) antibody peroxidase conjugate ( chemicon ) was used . dna fragments containing the putative regulatory region upstream to mir - 222 / mir - 221 ( from + 1 ˜− 150 nt , + 1 ˜− 600 , + 1 ˜− 1000 (+ 1 position corresponds to the 5 ′ terminus of mir - 222 hairpin ) were amplified and cloned in pgl3basic ( promega ). meg01 cells were transfected with lipofectamine 2000 ( invitrogen ), 1 . 0 g of pgl3basic empty vector or of pgl3 containing the above genomic fragments , 200 ng of renilla luciferase expression construct prl - tk ( promega ) and met , c - jun , c - fos sirnas . after 48 h , 4 cells were lysed and assayed with dual luciferase assay ( promega ) according to the manufacturer &# 39 ; s instructions . three independent experiments were performed in triplicate . the primers utilized for the cloning were the followings : real - time pcr was performed using a standard taqman pcr kit protocol on an applied biosystems 7900ht sequence detection system ( applied biosystems ). the 10 μl pcr reaction included 0 . 67 μl rt product , 1 μl taqman universal pcr master mix ( applied biosystems ), 0 . 2 mm taqman probe , 1 . 5 mm forward primer and 0 . 7 mm reverse primer . the reactions were incubated in a 96 - well plate at 95 ° c . for 10 mm , followed by 40 cycles of 95 ° c . for 15 s and 60 ° c . for 1 min . all reactions were run in triplicate . the threshold cycle ( ct ) is defined as the fractional cycle number at which the fluorescence passes the fixed threshold . the comparative ct method for relative quantization of gene expression ( applied biosystems ) was used to determine mirna expression levels . the y axis represents the 2 (- ct ), or the relative expression of the different mirs . mirs expression was calculated relative to u44 and u48 rrna and multiplied by 104 . experiments were carried out in triplicate for each data point , and data analysis was performed by using software ( bio - rad ). total rna was extracted with trizol solution ( invitrogen according to the manufacturer &# 39 ; s instructions and the integrity of rna was assessed with an agilent bioanalizer 2100 ( agilent , palo alto , calif ., usa ). northern blotting was performed as described by calin et al ., 2002 . the oligonucleotides used as probes were the complementary sequences of the mature mirna ( mirna registry ): 2 ′- o - methyl ( 2 ′- o - me ) oligoribonucleotides were synthesized by fidelity . the sequences of 2 ′- o - me - anti - mir - 221 and 2 ′- o - me - anti - mir - 222 are as follows : 2 ′- o - me - gfp mir ( 5 ′- aaggcaagcugacccugaagu [ seq id no : 17 ]) was used as control . cells were grown in six well plate ( 1 . 7 × 10 6 per well ) for 24 h and transfected 100 nmoli / l / well of 2 ′- o - me - oligoribonucleotides using lipofectamine 2000 . rna and proteins were extracted after 72 h from the transfection . cells were plated in 96 - well plates in triplicate and incubated at 37 ° c . in a 5 % co 2 incubator . super - killer trail ( alexis biochemicals ) was used for 24 - 48 h at 400 ng ml - 1 . cell viability was examined with 3 -( 4 , 5 - dimethylthiazol - 2 - yl )- 2 , 5 - dipheniltetrazolium bromide ( mtt )- cell titer 96 aqueous one solution cell proliferation assay ( promega ), according to the manufacturer &# 39 ; s protocol . metabolically active cells were detected by adding 20 μl of mtt to each well . after 1 h of incubation , the plates were analyzed in a multilabel counter ( bio - rad laboratories ). apoptosis was assessed using annexin v - fitc apoptosis detection kits followed by flowcytometric analysis and caspase 3 / 7 activity . cells were seeded at 1 . 8106 cells per 100 mm dish , grown overnight in 10 % fbs / rpmi , washed with phosphate - buffered saline ( pbs ) and then treated for 24 h with 400 ng / ml trail . following incubation , cells were washed with cold pbs and removed from the plates by trypsinization . the resuspended cells were washed with cold pbs and stained with fitc - conjugated annexin v antibody according to the manufacturer &# 39 ; s instructions ( roche applied science ). cells ( 5 × 10 5 per sample ) were then subjected to flow cytometric analysis . flow cytometry analyses were done as described ( garofalo et al ., 2007 ). the fraction of h460 cells treated with trail was taken as the apoptotic cell population . the percentage of apoptosis indicated was corrected for background levels found in the corresponding untreated controls . statistical analysis was done using two sample t test , assuming equal variance , and p value was calculated based on two - tailed test . for detection of caspase 3 / 7 activity , cells were cultured in 96 - well plates and treated with trail 400 ng / ml and analyzed using caspase - glo 3 / 7 assay kit ( promega ) according to the manufacturer &# 39 ; s instructions . continuous variables are expressed as mean values ± standard deviation ( s . d .). chromatin immunoprecipitation was performed as described by de belle et al ., 2000 with slight modifications . cells ( 5106 ) from h460 , calu - 1 and snu - 387 cell lines were fixed in 1 % formaldehyde for 10 min at 37 ° c . cells were washed with ice - cold 1 pbs , scraped in 1 × pbs plus protease inhibitors , and collected by centrifugation . cell pellets , resuspended in cell lysis buffer [ 50 mmol / l tris - hcl ( ph 8 . 0 ), 10 mmol / l edta , and 1 % sds ] plus protease inhibitors , were then sonicated . dna - protein complexes were immunoprecipitated using 5 g of the anti - c - jun antibody ( santa cruz ) or with rabbit polyclonal igg control ( zymed ). cross - links in the immunoprecipitated chromatin were reversed by heating with proteinase k at 65 ° c . overnight , and dna was purified by the minelute reaction cleanup column ( qiagen ) and resuspended in water . the purified chromatin was subjected to pcr and the products were analyzed by gel electrophoresis using 2 % agarose . the following primers were used : cells were cultured to 80 % confluence and transiently transfected using lipofectamine 2000 with 100 nm anti - pten or with 100 nm anti - timp3 smartpool sirnas or control sirnas ( dharmacon ), a pool of four target specific 20 - 25 nt sirnas designed to knock down gene expression . mirna locked nucleic acid in situ hybridization of formalin fixed , paraffin - embedded tissue section . in situ hybridization ( ish ) was carried out on deparaffinized human lung and liver tissues using previously published protocol ( nuovo et al ., 2009 ), which includes a digestion in pepsin ( 1 . 3 mg / ml ) for 30 minutes . the sequences of the probes containing the six dispersed locked nucleic acid ( lna ) modified bases with digoxigenin conjugated to the 5 ′ end were : the probe cocktail and tissue mirna were co - denatured at 60 ° c . for 5 minutes , followed by hybridization at 37 ° c . overnight and a low stringency wash in 0 . 2 × ssc and 2 % bovine serum albumin at 4 ° c . for 10 minutes . the probe - target complex was seen due to the action of alkaline phosphatase on the chromogen nitroblue tetrazolium and bromochloroindolyl phosphate ( nbt / bcip ). negative controls included the use of a probe which should yield a negative result in such tissues . no counterstain was used , to facilitate co - labeling for pten , timp3 and met proteins . after in situ hybridization for the mirnas , as previously described ( nuovo et al ., 2009 ), the slides were analyzed for immunohistochemistry using the optimal conditions for pten ( 1 : 800 , cell conditioning for 30 minutes ), timp3 ( 1 : 1300 , cell conditioning for 30 minutes ) and met ( 1 : 20 , cell conditioning for 30 minutes ). for the immunohistochemistry , the inventors used the ultrasensitive universal fast red system from ventana medical systems . the inventors used normal liver and lung tissues as controls for these proteins . the percentage of tumor cells expressing pten , timp3 and mir - 221 and mir - 222 was then analyzed with emphasis on co - localization of the respective targets ( mir - 221 or mir - 222 and either pten or timp3 ). media , sera and antibiotics for cell culture were from life technologies , inc . ( grand island , n . y ., usa ). protein electrophoresis reagents were from bio - rad laboratories ( richmond , va ., usa ) and western blotting and ecl reagents from ge healthcare ( piscataway , n . j ., usa ). all other chemicals were from sigma ( st louis , mo ., usa ). human calu - 1 and a549 cell lines were grown in dulbecco &# 39 ; s modified eagle &# 39 ; s medium containing 10 % heat - inactivated fetal bovine serum ( fbs ) and with 2 mm l - glutamine and 100 uml - 1 penicillin - streptomycin . he1299 , h460 , a459 , h1975 , h1299 , h1573 , h23 , plcrf15 , snu - 387 , snu - 423 , snu - 475 cell lines were grown in rpmi containing 10 % heat - inactivated fbs and with 2 mm l - glutamine and 100 uml - 1 penicillin - streptomycin . sk - hepl , hep - g2 , hepg2c3a , hep3b , huh7 were grown in mem supplemented with 10 % fetal bovine serum , 2 mm l - glutamine and 100 uml - 1 penicillin - streptomycin . normal hepatocytes were grown in hepatocytes growth medium ( sciencell ) supplemented with 10 % fetal bovine serum , 2 mm l - glutamine , 1 % of hepatocyte growth supplement ( hgs ) and 100 uml - 1 penicillin - streptomycin . transwell insert chambers with 8 - nm porous membrane ( greiner bio - one ) were used for the assay . cells were washed three times with pbs and added to the top chamber in serum - free media . the bottom chamber was filled with media containing 10 % fbs . cells were incubated for 24 h at 37 ° c . in a 5 % co2 humidified incubator . to quantify migrating cells , cells on the top chamber were removed by using a cotton - tipped swab , and the migrated cells were fixed in pbs , 25 % glutaraldehyde and stained with crystal violet stain , visualized under a phase - contrast microscope , and photographed . cristal violet - stained cells were moreover solubilized in acetic acid and methanol ( 1 : 1 ) and absorbance was measured at 595 nm . the results are means of three independent experiments ± s . d . h460 and sk - hep - 1 cells were placed into the top chamber of a bd falcon hts fluoroblok insert with a membrane containing 8 - nm pores ( bd biosciences ) in 300 l of serum - free dulbecco &# 39 ; s modified eagle medium in triplicate . the inserts were placed into the bottom chamber wells of a 24 - well plate containing dulbecco &# 39 ; s modified eagle medium media and fetal bovine serum ( 10 %) as chemoattractant . cells that migrated through the pores of the membrane to the bottom chamber were labeled with 8 g / ml calcein - am ( molecular probes , eugene , oreg .) in phosphate - buffered saline ( pbs ) for 30 minutes at 37 ° c . the fluorescence of migrated cells was quantified using a fluorometer at excitation wavelengths of 485 nm and emission wavelengths of 530 nm and expressed as arbitrary fluorescence units . data are expressed as mean ± standard error of 4 separate determinations . pten and timp3 cdnas were obtained from h460 cells rna by using the one step rt - pcr kit ( invitrogen ) according to the manufacturer &# 39 ; s instructions . the pcr fragments were amplified by using the following primers : and then cloned in pcruz - ha ( santa cruz ) after digestion with noti - xbai ( pten ) or noti - bglii ( timp3 ). all vectors were controlled by sequencing . bioinformatic analysis was performed by using these specific programs : targetscanl , pictar2 and rnhybrid3 . 1 http :// www . targetscan . org / 2 http :// pictar . bio . nyu . edu / 3 http :// bibiserv . techfak . uni - bielefeld . de / method of treating hcc in patients exhibiting trail sensitive trail expression pattern in hcc tumor samples this example describes a method of selecting and treating hcc patients that are likely to have a favorable response to trail treatment as a therapy . for some hcc patients , trail therapy can prolong survival ( sun et al ., j . cancer res . clin . oncol . 132 ( 7 ): 458 - 465 , 2006 ). however , it would be beneficial to identify patients that are most likely to benefit from trail therapy prior to initiating treatment . it is now disclosed herein that the prognosis of hcc patients expressing trail sensitive trail expression pattern in tumor samples relative to a control ( such as non - cancerous liver tissue obtained from the same patient ) significantly improves after treatment with trail . in contrast , patients expressing trail resistant trail expression pattern in tumor samples do not exhibit a significant increase in survival following trail treatment and thus are not good candidates for such adjunctive treatment . a patient diagnosed with hcc first undergoes liver resection with an intent to cure . hcc tumor and non - cancerous tissue samples are obtained from the portion of the liver tissue removed from the patient . rna is then isolated from the tissue samples using any appropriate method for extraction of small rnas that are well known in the art , such as by using trizol ™. purified rna is then subjected to rt - pcr using primers specific for c - jun and mir - 221 and mir - 222 , optionally in conjunction with pten and / or timp3 . the assay may also be run with mir - 221 and mir - 222 and pten and / or timp3 , without c - jun . these assays are run to determine the expression level of the pertinent rna in the tumor and non - cancerous tissues . if trail sensitive expression pattern is found in the tumor tissue relative to the non - cancerous tissue , the patient is a candidate for trail adjunctive therapy . accordingly , the patient is treated with a therapeutically effective amount of trail a according to methods known in the art . the dose and dosing regimen of trail will vary depending on a variety of factors , such as health status of the patient and the stage of the hcc . typically , trail is administered in many doses over time . alternative treatment method for hcc patients with low expression of mir - 26 this example describes a method of treating a patient diagnosed with hcc in the absence of liver resection . to determine whether a patient diagnosed with hcc is a good candidate for trail therapy , a hcc tumor sample is obtained from the patient that has not undergone liver resection , along with a non - cancerous liver tissue sample . the tissue samples can be obtained according to any method known in the art . for example , the tissue samples can be obtained by performing a biopsy procedure using a hypodermic needle to remove the desired tissues . rna is then isolated from the tissue samples using any appropriate method for extraction of small rnas that are well known in the art , such as by using trizol ™. purified rna is then subjected to rt - pcr using primers specific for mir - 26 to determine the expression level of mir - 26 in the tumor and non - cancerous tissues . if trail sensitive trail expression pattern is found in the tumor tissue relative to the non - cancerous tissue , the patient is a candidate for therapy . accordingly , the patient is treated with a therapeutically effective amount of therapeutic according to methods known in the art . the dose and dosing regimen will vary depending on a variety of factors , such as health status of the patient and the stage of the hcc . typically , treatment is administered in many doses over time . method of treating hcc in patients exhibiting trail resistant trail expression pattern in hcc tumor samples this example describes a method of treating a patient diagnosed with hcc if the patient exhibits a trail resistant trail expression pattern in the hcc tumor . a patient diagnosed with hcc first undergoes liver resection with an intent to cure . hcc tumor and non - cancerous tissue samples are obtained from the portion of the liver tissue removed from the patient . rna is then isolated from the tissue samples using any appropriate method for extraction of small rnas that are well known in the art , such as by using trizol ™. purified rna is then subjected to rt - pcr using primers specific for mir - 26 to determine the expression level of mir - 26 in the tumor and non - cancerous tissues . if trail resistant trail expression pattern is found in the tumor tissue relative to the non - cancerous tissue , the patient is unlikely to respond favorably to trail adjunctive therapy . accordingly , the patient does not receive trail therapy but is considered for other treatment modalities to convert to trail sensitivity . alternatively , the patient is monitored for post - operative signs of disease recurrence . in one particular aspect , there is provided herein a method of diagnosing whether a subject has , or is at risk for developing , hepatocellular carcinoma ( hcc ). the method generally includes measuring the trail expression pattern in a test sample from the subject and determining whether the trail expression pattern in the test sample deviates relative to the level of a trail expression pattern in a control sample , is indicative of the subject either having , or being at risk for developing , hcc . in certain embodiments , the level of the at least one gene product is measured using northern blot analysis . also , in certain embodiments , the level of the at least one gene product in the test sample is less than the level of the corresponding mir gene product in the control sample , and / or the level of the at least one mir gene product in the test sample is greater than the level of the corresponding mir gene product in the control sample . the level of the at least one mir gene product can be measured by reverse transcribing rna from a test sample obtained from the subject to provide a set of target oligodeoxynucleotides ; hybridizing the target oligodeoxynucleotides to a microarray comprising mirna - specific probe oligonucleotides to provide a hybridization profile for the test sample ; and , comparing the test sample hybridization profile to a hybridization profile generated from a control sample . an alteration in the signal of at least one mirna is indicative of the subject either having , or being at risk for developing , hcc . in another aspect , there is provided herein are methods of treating hcc in a subject , where the signal of at least one mirna , relative to the signal generated from the control sample , is de - regulated ( e . g ., down - regulated and / or up - regulated ). also provided herein are methods of diagnosing whether a subject has , or is at risk for developing , a hcc associated with one or more adverse prognostic markers in a subject , by reverse transcribing rna from a test sample obtained from the subject to provide a set of target oligodeoxynucleotides ; hybridizing the target oligodeoxynucleotides to a microarray comprising mirna - specific probe oligonucleotides to provide a hybridization profile for the test sample ; and , comparing the test sample hybridization profile to a hybridization profile generated from a control sample . an alteration in the signal is indicative of the subject either having , or being at risk for developing , the cancer . also provided herein are methods of treating hcc in a subject who has hcc in which at least two gene products of the trail expression pattern genes are down - regulated or up - regulated in the cancer cells of the subject relative to control cells . when the at least two gene products are down - regulated in the cancer cells , the method comprises administering to the subject an effective amount of at least two isolated gene products , such that proliferation of cancer cells in the subject is inhibited . when two or more gene products are up - regulated in the cancer cells , the method comprises administering to the subject an effective amount of at least one compound for inhibiting expression of at least one gene product , such that proliferation of cancer cells in the subject is inhibited . also provided herein are methods of treating hcc in a subject , comprising : determining the amount of at least two trail expression gene products in hcc cells , relative to control cells ; and , altering the amount of the gene products expressed in the hcc cells by : administering to the subject an effective amount of at the at least two gene products , if the amount of the gene products expressed in the cancer cells is less than the amount of the gene products expressed in control cells ; or administering to the subject an effective amount of at least one compound for inhibiting expression of the at least two gene products , if the amount of the gene product expressed in the cancer cells is greater than the amount of the gene product expressed in control cells , such that proliferation of cancer cells in the subject is inhibited . also provided herein are pharmaceutical compositions for treating trail resistant cancer , comprising at least two isolated trail expression pattern gene product and a pharmaceutically - acceptable carrier . in a particular embodiment , the pharmaceutical compositions comprise gene products corresponds to gene products that are down - regulated in hcc cells relative to suitable control cells . in another particular embodiment , the pharmaceutical composition comprises at least one expression regulator ( for example , an inhibitor ) compound and a pharmaceutically - acceptable carrier . also provided herein are pharmaceutical compositions that include at least one expression regulator compound that is specific for a gene product that is up - or down - regulated in hcc cells relative to suitable control cells . any of the compositions described herein may be comprised in a kit . in a non - limiting example , reagents for isolating mirna , labeling mirna , and / or evaluating an mirna population using an array are included in a kit . the kit may further include reagents for creating or synthesizing mirna probes . the kits will thus comprise , in suitable container means , an enzyme for labeling the mirna by incorporating labeled nucleotide or unlabeled nucleotides that are subsequently labeled . it may also include one or more buffers , such as reaction buffer , labeling buffer , washing buffer , or a hybridization buffer , compounds for preparing the mirna probes , and components for isolating mirna . other kits may include components for making a nucleic acid array comprising oligonucleotides complementary to mirnas , and thus , may include , for example , a solid support . for any kit embodiment , including an array , there can be nucleic acid molecules that contain a sequence that is identical or complementary to all or part of any of the sequences herein . the components of the kits may be packaged either in aqueous media or in lyophilized form . the container means of the kits will generally include at least one vial , test tube , flask , bottle , syringe or other container means , into which a component may be placed , and preferably , suitably aliquoted . where there is more than one component in the kit ( labeling reagent and label may be packaged together ), the kit also will generally contain a second , third or other additional container into which the additional components may be separately placed . however , various combinations of components may be comprised in a vial . the kits of the present invention also will typically include a means for containing the nucleic acids , and any other reagent containers in close confinement for commercial sale . such containers may include injection or blow - molded plastic containers into which the desired vials are retained . when the components of the kit are provided in one and / or more liquid solutions , the liquid solution is an aqueous solution , with a sterile aqueous solution being one preferred solution . other solutions that may be included in a kit are those solutions involved in isolating and / or enriching mirna from a mixed sample . however , the components of the kit may be provided as dried powder ( s ). when reagents and / or components are provided as a dry powder , the powder can be reconstituted by the addition of a suitable solvent . it is envisioned that the solvent may also be provided in another container means . the kits may also include components that facilitate isolation of the labeled mirna . it may also include components that preserve or maintain the mirna or that protect against its degradation . the components may be rnase - free or protect against rnases . also , the kits can generally comprise , in suitable means , distinct containers for each individual reagent or solution . the kit can also include instructions for employing the kit components as well the use of any other reagent not included in the kit . instructions may include variations that can be implemented . it is contemplated that such reagents are embodiments of kits of the invention . also , the kits are not limited to the particular items identified above and may include any reagent used for the manipulation or characterization of mirna . it is also contemplated that any embodiment discussed in the context of an mirna array may be employed more generally in screening or profiling methods or kits of the invention . in other words , any embodiments describing what may be included in a particular array can be practiced in the context of mirna profiling more generally and need not involve an array per se . it is also contemplated that any kit , array or other detection technique or tool , or any method can involve profiling for any of these mirnas . also , it is contemplated that any embodiment discussed in the context of an mirna array can be implemented with or without the array format in methods of the invention ; in other words , any mirna in an mirna array may be screened or evaluated in any method of the invention according to any techniques known to those of skill in the art . the array format is not required for the screening and diagnostic methods to be implemented . the kits for using mirna arrays for therapeutic , prognostic , or diagnostic applications and such uses are contemplated by the inventors herein . the kits can include an mirna array , as well as information regarding a standard or normalized mirna profile for the mirnas on the array . also , in certain embodiments , control rna or dna can be included in the kit . the control rna can be mirna that can be used as a positive control for labeling and / or array analysis . the methods and kits of the current teachings have been described broadly and generically herein . each of the narrower species and sub - generic groupings falling within the generic disclosure also form part of the current teachings . this includes the generic description of the current teachings with a proviso or negative limitation removing any subject matter from the genus , regardless of whether or not the excised material is specifically recited herein . also provided herein are the preparation and use of mirna arrays , which are ordered macroarrays or microarrays of nucleic acid molecules ( probes ) that are fully or nearly complementary or identical to a plurality of mirna molecules or precursor mirna molecules and that are positioned on a support material in a spatially separated organization . macroarrays are typically sheets of nitrocellulose or nylon upon which probes have been spotted . microarrays position the nucleic acid probes more densely such that up to 10 , 000 nucleic acid molecules can be fit into a region typically 1 to 4 square centimeters . microarrays can be fabricated by spotting nucleic acid molecules , e . g ., genes , oligonucleotides , etc ., onto substrates or fabricating oligonucleotide sequences in situ on a substrate . spotted or fabricated nucleic acid molecules can be applied in a high density matrix pattern of up to about 30 non - identical nucleic acid molecules per square centimeter or higher , e . g . up to about 100 or even 1000 per square centimeter . microarrays typically use coated glass as the solid support , in contrast to the nitrocellulose - based material of filter arrays . by having an ordered array of mirna - complementing nucleic acid samples , the position of each sample can be tracked and linked to the original sample . a variety of different array devices in which a plurality of distinct nucleic acid probes are stably associated with the surface of a solid support are known to those of skill in the art . useful substrates for arrays include nylon , glass and silicon . the arrays may vary in a number of different ways , including average probe length , sequence or types of probes , nature of bond between the probe and the array surface , e . g . covalent or non - covalent , and the like . the labeling and screening methods described herein and the arrays are not limited in its utility with respect to any parameter except that the probes detect mirna ; consequently , methods and compositions may be used with a variety of different types of mirna arrays . in view of the many possible embodiments to which the principles of our invention may be applied , it should be recognized that the illustrated embodiments are only preferred examples of the invention and should not be taken as a limitation on the scope of the invention . rather , the scope of the invention is defined by the following claims . we therefore claim as our invention all that comes within the scope and spirit of these claims .	2
with reference to fig1 and fig2 the schematic drawings show a preferred embodiment of the invention which includes : an elastic filler , such as a sponge ( 3 ), enveloped by the internal lining ( 2 ); an electromagnetic hammering mode massage device ( 4 ) installed centrally within the elastic filler of sponge ( 3 ), including : an electronic circuit box ( 5 ), connected via a conductor ( 6 ) to a control box ( 7 ), installed in a clamping plate frame of the electromagnetic hammering mode massage device , the control box ( 7 ) is fitted with a power supply socket fixed to a side of the cushion by a securing ring ( 10 ) ( see fig2 ). a potentiometer ( 8 ) is provided to perform and adjust the hammering mode massage . as shown in fig3 the electromagnetic hammering mode massage device ( 4 ) comprises an electromagnetic hammering mechanism ( 35 ), a clamping plate frame ( 29 ), and an electric control unit including a circuit box ( 5 ). the electromagnetic hammering mechanism ( 35 ) of the preferred embodiment is situated centrally within the clamping frame ( 29 ). the clamping plate frame ( 29 ) includes a rear plate ( 11 ) and a front plate ( 23 ) with four supporting columns ( 22 ) of equal length are mounted there between so that the front plate ( 23 ) and the rear plate ( 11 ) are spaced parallel to each other . on both the rear plate ( 11 ) and the front plate ( 23 ), holes are provided for mounting the ends of the supporting columns thereto . the four supporting columns ( 22 ) are distributed evenly around a hole ( 30 ) formed in the front plate ( 23 ). a shock - absorbing block ( 21 ) is fixed to a rear surface of the front plate ( 23 ) around the hole ( 30 ) of the front plate ( 23 ). the electromagnetic hammering mechanism ( 35 ) includes a stop block ( 25 ), having a centrally - located through hole formed therein , which is mounted in a through hole formed in the center of a stop plate ( 24 ). a coil frame ( 16 ), wound to form a coil ( 17 ) and mounted in a magnet yoke ( 18 ), has a cylindrical through hole formed in the center of the coil frame ( 16 ). an end of the stop block ( 25 ) which protrudes through the stop plate ( 24 ) is fitted within one end of the coil frame through hole . the magnet yoke ( 18 ) is fastened to the stop plate ( 24 ) so that the coil frame ( 16 ) is also fixed on the stop plate ( 24 ). the magnet yoke ( 18 ) is also provided with a through hole which aligns with the center through hole of the coil frame ( 16 ). a cylindrical armature ( 14 ) is fastened at a lower end to a stop ring ( 12 ). an upper end of the armature ( 14 ) passes through the through hole of the magnet yoke ( 18 ) into the center through hole of the coil frame ( 16 ). the upper end of the armature ( 14 ) is provided with a threaded hole . a shock - absorbing gasket ( 13 ) is installed between the top surface of the stop ring ( 12 ) and the bottom face of the magnet yoke ( 18 ). a sliding rod ( 15 ), which has a threaded lower end , is slideably disposed in the through hole of the stop block ( 25 ). the threaded end of the sliding rod ( 15 ) is engaged with the threaded hole in the upper end of the armature ( 14 ). a hammering head ( 28 ) is attached to the upper end of the sliding rod ( 15 ). a shock absorber structure consisting of a compressible spring ( 26 ) and a shock absorbing ring ( 27 ) is mounted on the sliding rod ( 15 ) between the top face of the stop block ( 25 ) and the bottom face of the hammering head ( 28 ). the stop plate ( 24 ) is provided with guide holes which align with the columns ( 22 ) which allow the stop plate ( 24 ) to slide along the columns ( 22 ). a flange ( 20 ) is disposed in alignment with and immediately under each guide hole of the stop plate ( 24 ). a compressible spring ( 19 ) is fitted around each supporting column ( 22 ) between a lower end face of the flange ( 20 ) and the top surface of the rear plate ( 11 ) so that the whole electromagnetic hammering mechanism ( 35 ) can be elastically installed in the clamping plate frame . after installation of the electromagnetic hammering mechanism in the clamping plate frame , the hammering head ( 28 ) should protrude from the top surface of the front plate ( 23 ) through hole ( 30 ). fig4 shows a block diagram of an electric control unit of the present invention which includes a pulse shaping circuit ( 31 ), a massage status controlling circuit ( 32 ), a pulse - width regulating circuit ( 33 ), and an electronic switch ( 34 ). the beat output of the pulse - shaping circuit ( 31 ) regulates the hammering speed ; the massage status controlling circuit ( 32 ) is brought into operation through the selection switch following the pulse - shaping . hammering intensity is regulated by changing the pulse width with the pulse - width adjustment circuit ( 33 ). the pulse current output from the electronic switch ( 34 ) is transmitted to the magnet coil ( 17 ) of the electromagnetic hammering mechanism ( 35 ) so as to produce an electromagnetic force for driving the hammering head ( 28 ) resulting in the hammering mode massage action . though the preferred embodiment employs only one electromagnetic hammering mechanism , fig4 shows the circuit black diagram for a plurality of electromagnetic hammering mechanisms represented in the block diagram by reference numbers having a subscript 1 - n . the electronic circuit of the present invention is designed to use either alternating or direct current power supply with a voltage of 12v - 220v . it can also incorporate an isolation transformer or a safety device against electric shock . additionally , the device may be provided with a protection function to stop operation upon absence of the person using the device , or an automatic shut - off function activated by temperature control . the device may also be equipped with an audio device for music or a radio set . it is to be understood that the outward appearance of the soft cushion of the present invention , the surface material used for external cover ( 1 ) and the filling material may be selected to meet various requirements . furthermore , changes may be made in details of the other components within the principles of the invention to the full extent indicated by the broad general meaning of the terms in which the appended claims are expressed . for instance , more than one hammering mode massage mechanism may be installed within the soft cushion .	8
reference will now be made in detail to the presently preferred embodiments of the invention . each example is provided by way of explanation of the invention , not limitation of the invention . it will be apparent to those skilled in the art that various modifications and variations can be made in the invention without departing from the scope or spirit of the invention . it is intended that the present invention cover such modifications and variations as come within the scope of the claims and their equivalents . in accordance with the objects of the invention , and as illustrated in fig1 an adjustable surface mount adapter 10 is provided . adapter 10 includes an inner wall mount 12 for being disposed on one side of the wall . inner wall mount 12 includes wall contacting surface 14 . the shape and configuration of inner wall mount 12 and wall contacting surface 14 illustrated in fig1 is illustrated as a mere example of an embodiment of the invention . it should be understood that inner wall mount 12 can take on any shape such as hexagonal , square , or the like . in addition , wall contacting surface 14 may take on the form of an annular ring as illustrated in fig1 or , can assume any other suitable configuration such as alternate projections , a flat surface encompassing substantially the entire back surface of wall mount 12 , or the like . in addition , it is within the scope of the claims to include a washer , gasket , or insulation material between inner wall mount 12 and a wall with the washer , gasket , or material thus being the wall contacting surface 14 . inner wall mount 12 also includes a stem portion 16 . stem portion 16 is of a sufficient length to extend through a wall of predetermined thickness , for example for the adapter to be utilized for walls having a thickness of from 1 / 8 inch to 11 / 2 inches , stem portion 16 could be of a length of 21 / 4 inches from the wall contacting surface 14 . it should be understood that stem portion 16 can be of any length depending upon the thickness of the wall adapter 10 is to be utilized with . stem portion 16 also includes a form locking outer diameter surface 18 over at least a portion thereof . in a preferred embodiment as illustrated in the figures , form locking surface 18 comprises a threaded surface 20 . however , it is within the scope of the invention that form locking surface 18 also include a ratcheted surface , a tongue in groove surface , or even a smooth surface to be cemented or glued . for ease of manufacture and assembly of adapter 10 , however , a threaded surface is preferred . inner wall mount 12 further defines an inner diameter 24 sufficient for a pipe of predetermined diameter to be inserted therein . for example , if inner wall mount 12 were to receive a 3 / 4 inch pipe , inner diameter 24 would be approximately 0 . 882 inches . it should be understood that stem portion 16 is essentially hollow and preferably is of the same inner diameter as inner diameter 24 in the mount 12 receiving the pipe . however , such is not a limitation of the invention . for example , in an alternative preferred embodiment , inner wall mount 12 may include a flange or similar structure essentially separating inner diameter portion 24 and stem portion 16 of the mount 12 . in this manner , a pipe inserted into inner diameter 24 would abut against flange 26 and it would not be essential that the inner diameter of stem portion 16 match that of portion 24 . a flange or like structure would also provide for easier alignment and gluing or securing of a pipe within mount 12 . surface mount adapter 10 also includes an outer wall mount 34 as illustrated in the figures . outer wall mount 34 also includes a wall contacting surface 42 and , as discussed above , the shape and configuration of mount 34 and wall contacting surface 42 illustrated in the figures is but a mere example of any suitable configuration . for example , mount 34 may have a hexagonal , circular , or any other profile . outer wall mount 34 includes a receiving portion 37 . receiving portion 37 has a form - locking inner diameter surface 38 for engagement with form - locking surface 18 of stem portion 16 . in the preferred embodiment , form - locking surface 38 is a threaded surface matching the threads on stem portion 16 . in this manner , outer wall mount 34 engages inner wall mount 12 by simply being screwed onto stem portion 16 . in this way , a wall is more or less squeezed between wall contacting surfaces 14 and 42 of mounts 12 and 34 respectively . thus , adapter 10 is non - movably secured directly to the wall and forms a rigid passage therethrough . outer wall mount 34 acts essentially as a nut which is threaded onto stem portion 1b . in this manner , once mount 34 has been secured to inner mount 12 through stem portion 16 , any manner of pipe , fixture , adapter , or the like can be fitted into the open end of stem portion 16 extending through the wall . in a preferred embodiment , as illustrated in fig3 a threaded adapter may be fitted into stem portion 16 for receiving a pipe , fixture , or the like having a diameter different from that of stem portion 16 . also , stem portion 16 may have an inner flange or collar reducing the extreme end diameter thereof . it is preferred that outer wall mount 34 also include a circumferential engagement portion 44 . preferably , portion 44 is formed in the shape of a hexagon or other flat sided configuration for engagement with a wrench so as mount 34 can be easily screwed or tightened onto inner mount 12 . alternatively , outer mount 34 may be simply hand tightened onto inner mount 12 . the components of the present invention preferably are formed of , and compatible with , conventional plastic plumbing materials , such as pvc and cpvc since these materials can be readily glued . other materials require welding or soldering and detract from the invention . fig2 illustrates another embodiment of inner wall mount 12 and stem portion 16 according to the invention . inner wall mount 12 depicted in fig2 would be used for a relatively thick wall and includes a non form - locking or non - engaging portion 22 for extension through the wall . in this embodiment , only form - locking surface 18 would be engaged by outer wall mount 34 . preferably , the stem portion of mount 20 is cut and a pipe of any desired length is inserted between the mount and threaded stem portion . alternatively , the non form - locking portion and threaded portion could comprise a single integral component . thus , it should be understood that the present invention is not limited to any particularly thickness of wall and can be suitably adapted for any type wall . in further accordance with the objects of the present invention , and as depicted in fig3 a plumbing system having a rigid through - wall connection is provided . plumbing system 50 illustrated in fig3 is but a mere example of a system within the scope of the present invention and is illustrated as a supply 30 and faucet or shower head 32 running through wall 28 . it should be understood however that fixture 32 may also be a drain and pipe 30 may also be a drain line instead of a supply header . the present plumbing system is not limited to any particular configuration but is applicable to any through - wall plumbing connection . in the embodiment of fig3 system 50 includes supply pipe 30 disposed on the inner side of wall 28 . inner wall mount 12 is also provided on the inner side of wall 28 and receives pipe 30 therein . inner wall mount 12 is essentially as discussed above and includes stem portion 16 extending through wall 28 having a threaded outer surface . on the outer side of wall 28 , outer wall mount 34 is provided having a threaded receiving portion for engagement with stem portion 16 . mount 34 has a flat sided circumferential portion 44 for allowing mount 34 to be threaded onto stem portion 16 , as discussed above . system 50 further includes plumbing fixture 32 being received in outer wall mount 34 . preferably , an adapter 26 is provided so that fixture 32 is readily removable from outer wall mount 34 . pipe 30 and adapter 26 are easily inserted and glued to mount 12 and stem portion 16 , respectively . also , it is within the scope of the present invention that inner diameter 24 of stem portion 16 be threaded near the end thereof for engagement with a threaded adapter of pipe . however , in the preferred embodiment of the system wherein the components are made of pvc or cpvc material , it is a relatively easy procedure to simply glue fixtures 30 and 32 into the respective mounts 12 and 16 . fixture 32 of the present system 50 can comprise , for example , a shower head , faucet , drain , isolation valve , or any conventional plumbing fixture .	4
the present invention is directed to an automatic , self stirring device for stove top and microwave oven cooking , as illustrated in the several figures , where like reference numerals identify like components or features throughout the various views . fig1 illustrates a first embodiment of the stirring device 10 of this invention , where such device is shown removably mounted over a cooking pot . the device comprises a housing 12 , a mounting system 14 to support said housing 12 , a downwardly extending rotating shaft 16 , and a pair of laterally extended , adjustable mixing blades 18 removably attached to the distal end 20 of shaft 16 . the housing 12 , generally rectangular in configuration and fabricated from a high temperature resistant plastic , such as high density polyethylene , comprises four upstanding side walls 22 , a top wall 24 , and a bottom wall 26 , where said bottom wall includes a central opening 28 communicating with the interior thereof . further , the respective side walls 22 include threaded recesses 30 into which components of the mounting system 14 are received . a first embodiment of the mounting system 14 preferably comprises four individually , extendable , telescopic arms 32 . each said arm includes a first arm segment 34 , threaded at one end 35 thereof for engaging a complementary threaded recess 30 in the housing side wall , and a second arm segment 36 slidably received within said first arm segment 34 . the distal end 38 of said second arm segment may include a downwardly projecting stop member 40 , fabricated from rubber , for example , for engaging the periphery of the cooking pot when in the extended position . biasing the second arm segment and stop member 40 against the cooking pot is an internal compression spring 42 . as best seen in fig3 the outer end 43 of the first arm may be provided with an inwardly directed annular flange 45 . cooperating with said flange 45 is an annular rim or stop 47 about the second arm 36 to prevent it from prematurely releasing from the first arm 34 . by this arrangement , the housing 12 may be centrally disposed over a variety of sized circular or rectangular cooking pots . the rotating shaft 16 and adjustable mixing blades 18 are best illustrated in fig1 and 2 . in order to position the blades in close proximity to the bottom of the cooking pot , the rotating shaft 16 preferably comprises a pair telescopically engaged upper and lower shaft segments 44 , 46 , respectively . a first end of upper shaft segment 44 is internally threaded to engage threaded stub 48 , the external rotary member extending from the power source within the housing 12 and extending through opening 28 . the opposite end is provided with an internally positioned , v - shaped plastic latching member 50 , wedged therewithin , where one end thereof includes a nibble 52 communicating exteriorly thereof through an opening 54 . slidably engaging the opposite end is lower shaft segment 46 , where said segment includes a series of openings 56 . these openings 56 cooperate with the latching member 50 to axially position the respective shaft segments to the desired length . the free or distal end of lower shaft segment 46 is provided with a spring biased clip 58 having a blade support 60 extending downwardly through the bite thereof , fig2 . the blade support 60 includes a central wall 62 having a pair of outwardly curved flange members 64 , where the respective flanges along each side at wall 62 define a channel for slidably receiving a mixing blade 18 . by this arrangement , the blades may be positioned to a depth desired , then laterally extended or retracted , as desired , and locked by the clip 58 , to precisely fit the cooking pot . the blades 18 , as best seen in fig1 include a first series of larger holes 66 to facilitate mixing , and a series of smaller holes 68 for selectively engaging the clip 58 . fig3 and 4 are , respectively , side and plan views of the interior of the housing 12 showing primarily the gear mechanism for rotating the main shaft 70 , an extension of threaded stub 48 . the rotating mechanism includes a coiled , torsional spring 72 wound about and connected to said main shaft 70 , and a rubber speed control mechanism 74 to constrain or ensure the torsional spring 72 rotates at a designated rate . otherwise , the spring would unwind immediately . the half spring 76 is an important component of the timer or rotating mechanism . this half spring 76 winds as the pendulum like pallet 78 moves one way and then unwinds forcing the pallet 78 to move the other direction . the balance thereof keeps the oscillary motion initiated by the spring 76 and pallet 78 constant . the pallet 78 , like a pendulum , moves one direction as the escape wheel 80 rotates and then releases the wheel . as this sequence occurs , the other end of the pallet 78 rotates the shaft which loads the half spring 76 . in return , the half spring unwinds causing the pallet 78 to move in the other direction so that it engages the escape wheel again . this sequence of steps causes the escape wheel 80 to revolve once every eight seconds , which is the key to keeping accurate time . the main gear 82 is attached to the spring 72 which turns the gear 82 at a rate of one revolution every four seconds , which in turn is coordinated by the adjacent torque and timing gear trains 84 , 86 , respectively . the center wheel 90 rotates every 20 minutes to give validity to the manual rotary timer dial 92 . by this arrangement , the rotary mechanism provides a 300 : 1 ratio of teeth between the center wheel 90 and the main gear 82 so that the center wheel revolves once per twenty minutes and the main gear 82 revolves once per four seconds . the torsional gear 86 , toward the left of the respective figures , acts as an intermediate between the main gear 82 and the rubber speed control wheel 74 . the satellite wheels 94 , 96 function to transfer a slow angular rotation to the center wheel 90 to a fast revolution of the escape wheel 80 . to assist a non - attendant homemaker in using the stirring device of this invention , an alarm device may be incorporated into the system hereof . for example , when the stirring device runs down , a bell 97 , rung by the mallet 99 , may be provided . the spring 101 ( fig3 ) is loaded when the flexible pivot 103 pulls the mallet 99 back . the spring loads when the time expires forcing the mallet to strike the bell 97 . the flexible pivot 103 ( fig4 ) pulls the mallet back ( to load the spring ) when the main shaft 70 is turned from its initial position via component 105 , which enlarges the radius of the shaft . once the main shaft rotates back to its initial position , i . e ., signifying the expiration of time , the radius decreases by cam washer 107 , releasing the flexible pivot 103 which in turn unleashes the spring and mallet . a second embodiment for the mounting system for positioning the housing 12 of this invention is illustrated by the two views of fig5 and 6 . the modified mounting system comprises a central mounting plate 100 , having a central opening 102 for receiving the threaded stub 48 , as noted above . emanating from the mounting plate 100 is an inner network of connected leg segments 104 having a plurality of free legs 106 radially and angularly extending therefrom . the distal ends 108 of said free legs 106 may include a v - shaped , rubberized foot 109 to secure the network about the rim of the cooking pot . the network , including the free legs 106 , being fabricated from a high temperature resistant plastic , is sufficiently flexible to shift such legs to accommodate different dimensioned cooking vessels . finally , to position and fix the housing 12 the mounting plate 100 , plural apertures 110 may be provided to receive complementary feet 112 extending from the housing base . recognizing that exposed metal parts heated in a microwave oven can cause serious damage , the device hereof uses a heat resistant plastic , up to 500 degrees f ., that protects all metal parts , such as the stainless steel springs . while two embodiments have been described above on the mounting system , it is recognized that variations may be had with respect to the components hereof . therefore , while the invention has been disclosed in preferred forms only , it will be obvious to those skilled in the art that many additions , deletions and modifications can be made therein without departing from the spirit and scope of this invention , and that no undue limits should be imposed thereon except as set forth in the following claims .	1
embodiments of the present invention will now be described with reference to the accompanying drawings . fig1 is a diagram schematically illustrating the configuration of an automatic analyzer according to one embodiment of the present invention . the automatic analyzer according to this embodiment includes a sample rack loading unit 1 , an id reading unit 2 , a transfer line 3 , a reexamination transfer line 4 , analysis modules 5 , 6 , 7 , and 8 , a sample rack standby section 9 , a sample rack collecting unit 10 , a second reagent storing unit 100 , and an overall control computer 11 . the analysis modules 5 , 6 , 7 , and 8 and the sample rack loading unit 1 are equipped with control computers 12 , 13 , 14 , 15 , and 16 , respectively . in addition , the overall control computer 11 is equipped with an operation unit 18 and a display unit 19 . the sample rack loading unit 1 is a unit used to load a plurality of sample racks , each of which holds one or more samples ( specimens ). the analysis modules 5 , 6 , 7 , and 8 are units which are capable of separately performing automatic analysis ; they are located along and detachably connected to the transfer line 3 . the transfer line 3 leads to the analysis modules 5 , 6 , 7 , and 8 through lead - in lines 20 , 21 , 22 , and 23 , respectively , so that a sample ( specimen ) can be transferred therebetween . the number of the analysis modules may be arbitrarily determined ; in this embodiment , that number is four . further , in this embodiment , all of the analysis modules are biochemical analysis modules . the analysis modules may also include a combination of a biochemical analysis module and another analysis module ( for example , an electrolyte analysis module ). each of the analysis modules 5 , 6 , 7 , and 8 is provided with a sample dispenser 30 for dispensing a sample ( specimen ) that has been transferred to the analysis module with the sample placed in a sample rack ; and a reaction vessel 31 in which the sample ( specimen ) is made to react . in addition , each of the analysis modules 5 , 6 , 7 , and 8 is further provided with a reagent dispenser 32 for dispensing a reagent into the reaction vessel 31 into which the sample has been dispensed ; and a first reagent storing unit 33 that holds a reagent cassette filled with a reagent to be dispensed into the reaction vessel 31 . in this embodiment , each of the analysis modules 5 and 6 is provided with one first reagent storing unit 33 ; each of the analysis modules 7 and 8 is provided with two first reagent storing units 33 . as above , the analysis modules can each have a single or multiple first reagent storing units 33 . the second reagent storing unit 100 is connected via a reagent transfer line 101 to the first reagent storing units 33 included in the analysis modules 5 , 6 , 7 , and 8 . however , one analysis system need not have only one second reagent storing unit 100 as above ; instead , each analysis module within the analysis system can have one second reagent storing unit 100 . alternatively , one second reagent storing unit 100 can be provided for analysis modules of the same kind such as biochemical analysis modules or electrolyte analysis modules . the second reagent storing unit 100 includes a reagent supply unit 102 to which a user supplies reagents ; and a reagent identification unit 103 for identifying the kinds of the supplied reagents . moreover , the second reagent storing unit 100 may also have the function of refrigerating the reagents so as to store them for a long period of time . when the user operates the automatic analyzer on the basis of , for example , operation set 1 used for periodic medical examinations shown in table 1 , the number of required analysis items is limited , for operation set 1 is used for periodic medical examinations . however , the number of analysis samples registered for each analysis item is large . in contrast , in operation set 2 for nighttime shown in table 1 , many analysis items need to be analyzed due to various night - time analysis requests . however , the number of samples to be analyzed is not larger than those in regular medical examinations , and the number of analysis samples to be registered is thus smaller . when analysis items and the number of analysis samples are registered as an operation set proper for each automatic analyzer operation as above , various operation modes can be supported . a method for changing the operation mode of the automatic analyzer using an operation set will be described in accordance with the process flowchart shown in fig2 . in step 201 shown in fig2 , an operation set is registered for each operation mode . each of the operation sets constitutes a combination of analysis items and analysis sample numbers for the analysis items . in step 202 shown in fig2 , an operation set is selected . reagents required for the selected operation set are then checked to identify analysis items that can be analyzed by all the reagents placed in the first reagent storing unit 33 and in the second reagent storing unit 100 and to calculate the number of tests for each of the identified analysis items . next , in step 207 of fig2 , the operation set is changed . in step 208 of fig2 , reagents are replaced between the first reagent storing unit 33 and the second reagent storing unit 100 . in step 212 of fig2 , relevant reagents are placed in the first reagent storing unit 33 ; the reagents are in agreement with the analysis items and the number of planned analyses for each of the analysis items in the operation set . hereinafter , means for selecting reagents used for the analysis operation based on an operation set is referred to as “ reagent selection means ,” in which operation set analysis items each combined with the scheduled number of analyses are registered . next , steps executed by the reagent selection means will be sequentially described in detail . registration of an operation set , which corresponds to step 201 of fig2 , will be described with reference to fig3 . an operation set name is registered in an operation set list 401 . next , an analysis item is selected from an analysis item list 402 , and the selected analysis item is then added by use of an “ add ” button 403 . unnecessary items can be selected from among analysis items registered in an operation - set item list 404 and deleted by use of a “ delete ” button 405 . radio buttons 406 for selecting a method for setting the number of tests can be used to select the manual setting mode or the automatic setting mode . in the manual setting mode , the user manually sets the number of analyses for each analysis item . after that , the settings which have been set by use of the “ add ” button 403 and the “ delete ” button 405 are fixed by use of an “ update ” button 407 . lastly , the above settings are registered by use of a “ register ” button 408 . the above settings can be cancelled by use of a “ cancel ” button 409 . here , data relating to the operation set includes analysis item names ; the number of tests ; reagent names ; data ( bar code ) used to identify reagent cassettes ; the validity dates of reagents ; and analysis logs . these are written onto recording media built into the overall control computer 11 or the control computers 12 , 13 , 14 , and 15 . this makes it possible to easily set / register an operation set and to easily control transfer of reagents . as step 202 of fig2 , how to select an operation set will be described with reference to fig4 . an operation mode required at a certain point of time is selected from all registered operation sets shown in fig3 ( this embodiment shows a case where “ normal analysis ” is selected by use of an operation - set selection combo box 501 ). a “ check placed reagents ” button 502 is then clicked to identify analysis items that can be analyzed by all reagents placed in the first reagent storing unit 33 and in the second reagent storing unit 100 , and to calculate the number of tests corresponding to each of the analysis items that can be analyzed . in step 203 shown in fig2 , the identified analysis items that can be analyzed by use of all reagents placed in the first reagent storing unit 33 and in the second reagent storing unit 100 , and the calculated number of tests corresponding to each of the analysis items that can be analyzed , both of which have been obtained according to step 202 shown in fig2 , are compared with the analysis items of the operation set selected in fig4 and the scheduled number of analyses corresponding to each of the analysis items respectively . if it is judged that reagents required for the analysis operation based on the operation set are placed , a confirmation screen as shown in fig5 is displayed in step 204 shown in fig2 . clicking a “ close ” button 601 completes the confirmation . however , as a result of the placed reagent check in step 203 shown in fig2 , if it is judged that the reagents required for the analysis operation based on the operation set are not placed , insufficient reagents are displayed as shown in fig6 . this corresponds to step 205 shown in fig2 . in the example shown in fig6 , for the analysis items specified in the selected operation set , and for the scheduled number of analyses corresponding to each of the analysis items , information is displayed in a reagent information list 701 . the displayed information includes : a name of an analysis item for which a reagent is insufficient ; the scheduled number of analyses ( a ) specified in the operation set ; the number of analyses ( b ) that can be made by use of currently placed reagents ; and the insufficient number of tests ( c ). additionally , the number of new reagents ( d ) is displayed . this is the number of additional reagents required to satisfy the scheduled number of analyses specified in the operation set when the user is required to add new reagents . the number of new reagents ( d ) enables the user to know the number of reagents that should be placed . here , as step 206 shown in fig2 , the user places the reagents in the second reagent storing unit 100 . in this case , step 206 shown in fig2 may also be omitted . more specifically , the user is allowed not to place reagents if necessary although the user knows that the reagents are insufficient . in step 207 shown in fig2 , in order to place , in the first reagent storing unit 33 , reagents required for the scheduled number of tests specified in the operation set , a “ change operation set ” button 503 shown in fig4 is clicked . as a result , in step 208 , a reagent is transferred between the first reagent storing unit and the second reagent storing unit . in this case , an insufficient reagent is transferred from the second reagent storing unit 100 to the first reagent storing unit 33 so as to enable analyses , the number of which is equivalent to the scheduled number of analyses corresponding to each analysis item registered in the specified operation set . if the first reagent storing unit 33 does not have empty space for a reagent to be placed therein , with the result that no reagent can be transferred to the first reagent storing unit 33 , a reagent , which is not required for analysis items specified in the operation set , and which is not required for the scheduled number of analyses corresponding to each of the analysis items , is transferred from the first reagent storing unit 33 to the second reagent storing unit 100 . as a result , the first reagent storing unit 33 is provided with empty space for a required reagent to be placed therein . until all reagents , which are required for the analysis items specified in the operation set , and which are required for the scheduled number of analyses corresponding to each of the analysis items , are placed in the first reagent storing unit 33 , reagents are transferred between the first reagent storing unit 33 and the second reagent storing unit 100 . hereinafter , means for , when the first reagent storing unit does not have empty space for a reagent to be placed therein , with the result that all reagents required for analysis operation based on the operation set cannot be completely transferred to the first reagent storing unit , keeping the required reagent waiting in the second reagent storing unit , and for , when the first reagent storing unit is provided with empty space for a reagent to be placed therein , making a judgment as to whether or not to transfer the reagent to the first reagent storing unit , is referred to as “ transferability judgment means ”. incidentally , when a “ cancel ” button 504 shown in fig4 is clicked , the process proceeds to a next step without checking placed reagents , and without changing the operation set . in the case of an operation set in which the scheduled number of analyses corresponding to each analysis item is large , a large number of analysis items may require that a plurality of reagents be placed in the first reagent storing unit 33 on an analysis item basis . in this case , however , in step 209 shown in fig2 , such a situation can also be thought to occur that all reagent , which are required for analysis items specified in the operation set , and which are required for the scheduled number of analyses corresponding to each of the analysis items , cannot be completely transferred to the first reagent storing unit 33 . in such a case , as step 210 shown in fig2 , when reagents which could not be transferred to the first reagent storing unit 33 are kept waiting in the second reagent storing unit 100 ; the reagents are kept waiting in the second reagent storing unit 100 with a higher priority placed on a reagent , the required number of which is two or more for an identical item , and in decreasing order of the scheduled number of analyses specified in the operation set . this enables the first reagent storing unit 33 to always contain at least one reagent required for each of the analysis items specified in the operation set . on the completion of the reagent transfer operation , in step 211 shown in fig2 , a judgment is made again as to whether or not the reagents required for the operation set are placed in the first reagent storing unit 33 and in the second reagent storing unit 100 . the user &# 39 ; s attention is then attracted . here , if it is judged that the reagents required for the operation set are placed , the placement has been completed in step 212 shown in fig2 , and a confirmation screen as shown in fig7 is displayed . clicking a “ close ” button 801 completes the confirmation . however , if it is not judged that the reagents required for the operation set are placed in the first reagent storing unit 33 and in the second reagent storing unit 100 ( for example , there is a case where although insufficient reagents are displayed in step 205 shown in fig2 , the reagents have not yet been placed in step 206 shown in fig2 ; or there is a case where although the reagents have been placed in step 206 shown in fig2 , the reagents are insufficient for the scheduled number of analyses ), then , in step 213 , information is displayed again in the reagent information list 701 as shown in fig6 . the displayed information includes : a name of an analysis item for which a reagent is insufficient ; the scheduled number of analyses ( a ) specified in the operation set ; the number of analyses ( b ) that can be made by currently placed reagents ; the number of insufficient tests ( c ); and the number of new reagents ( d ) required when new reagents are placed . when analysis is started in step 214 shown in fig2 , a reagent which cannot be used for the analysis may occur for some reasons ( for example , the validity time is expired ) in step 215 shown in fig2 , a judgment is made as to whether or not the second reagent storing unit 100 contains a reagent to be transferred to the first reagent storing unit 33 . if it is judged that the second reagent storing unit 100 contains a reagent to be transferred to the first reagent storing unit 33 , a judgment is made in step 216 in fig2 as to whether or not the first reagent storing unit 33 has empty space for a reagent to be placed therein , or whether or not the first reagent storing unit 33 has an area in which a reagent which cannot be used for the analysis is placed . if it is judged to be “ yes ” in step 216 , a reagent kept waiting in the second reagent storing unit 100 is transferred to the empty space or the area in question in step 217 shown in fig2 . in contrast , if it is judged that the first reagent storing unit 33 has empty space for a reagent to be placed therein , or it is judged that the first reagent storing unit 33 has an area in which a reagent which cannot be used for the analysis is placed , then in step 218 , a reagent required for the analysis is transferred to the first reagent storing unit by replacing the reagent which cannot be used for the analysis or a reagent excessively stored in the first reagent storing unit with the reagent kept waiting in the second reagent storing unit 100 . as described above , each reagent kept waiting in the second reagent storing unit 100 is transferred to the first reagent storing unit 33 every time the first reagent storing unit 33 is provided with empty space for a reagent to be placed therein . as a result , even in the case of an operation set in which the scheduled number of analyses corresponding to each analysis item is large ( for example , an operation set used for multi - sample analysis ), analyses can be continued by use of reagents prepared before the start of the analyses . in step 201 shown in fig2 , when the scheduled number of analyses to be specified in the operation set is determined , if “ automatic ” is selected , the user is prompted to specify the day of the week and the time at which analysis will be started , and the day of the week and the time at which the analysis will be ended . accordingly , the scheduled number of analyses corresponding to each analysis item , which are to be made within the specified period of time , is automatically determined on the basis of the number of analyses corresponding to each analysis item recorded as past analysis recording . the number of analyses corresponding to each analysis item within a specified past period of time can be calculated by recording the number of analyses as the analysis recording with the number of analyses linked with information including the measurement date and time of each analysis item , and the kind of examination . hereinafter , the means for automatically determining the scheduled number of analyses corresponding to each analysis item defined in the operation set on the basis of the number of analyses corresponding to each analysis item recorded as the past analysis recording is referred to as “ scheduled - number - of - analyses automatic determination means ”. as an example of a method for automatically determining the scheduled number of analyses , for example , if a period of time is specified at the time of registering an operation set , the average number of analyses corresponding to each analysis item , which have been made within the same time range in the past corresponding to the specified period of time , is automatically determined as the scheduled number of analyses for the specified period of time . the above method will be described with reference to table 2 . when a period of time during which analyses are made , and an analysis item , are specified ( in table 2 , a time range from monday 9 : 00 to monday 17 : 00 is specified as the period of time ; and ast is specified as the analysis item ), analysis recording covering analyses of the specified analysis item made during the specified period of time is extracted from the past analysis recording to calculate the number of analyses for the specified period of time ( table 2 shows the number of analyses measured within the specified period of time on a week basis ). therefore , the average number of analyses measured within the same time range in the past is determined as the scheduled number of analyses for the specified period of time . as another example of the method for automatically determining the scheduled number of analyses , for example , if a period of time is specified at the time of registering an operation set , the maximum number of analyses which have been made within the same time range in the past is automatically determined as the scheduled number of analyses for the specified period of time . in this case , even if requests for analysis accidentally increases , it is possible to minimize the possibility that insufficient reagent will occur . in the above - described embodiments , the above processes can be automatically executed by recording a program for instructing a computer to function as the above means , or a program for instructing the computer to execute the above processes , in a computer - readable storage medium that is built into the overall control computer 11 or the control computers 12 , 13 , 14 , and 15 .	8
with reference now to the figures and in particular with reference to fig1 , a pictorial representation of a data processing system in which the present invention may be implemented is depicted in accordance with a preferred embodiment of the present invention . a computer 100 is depicted which includes system unit 102 , video display terminal 104 , keyboard 106 , storage devices 108 such as floppy drives and other types of permanent and removable storage media , and mouse 110 . additional input devices may be included with personal computer 100 , such as , for example , a joystick , touchpad , touch screen , trackball , microphone , and the like . computer 100 can be implemented using any suitable computer , such as an ibm eserver computer or intellistation computer , which are products of international business machines corporation , located in armonk , n . y . although the depicted representation shows a computer , other embodiments of the present invention may be implemented in other types of data processing systems , such as a network computer . computer 100 also preferably includes a graphical user interface ( gui ) that may be implemented by means of systems software residing in computer readable media in operation within computer 100 . fig2 is a block diagram of a data processing system in which the present invention may be implemented . data processing system 200 is an example of a computer , such as computer 100 in fig1 , in which code or instructions implementing the processes of the present invention may be located . data processing system 200 uses a peripheral component interconnect ( pci ) local bus architecture . although the depicted example employs a pci bus , other bus architectures such as accelerated graphics port ( agp ) and industry standard architecture ( isa ) may be used . processor 202 and main memory 204 connect to pci local bus 206 through pci bridge 208 . pci bridge 208 also may include an integrated memory controller and cache memory for processor 202 . additional connections to pci local bus 206 may be made through direct component interconnection or through add - in connectors . in the depicted example , local area network ( lan ) adapter 210 , small computer system interface ( scsi ) host bus adapter 212 , and expansion bus interface 214 connect to pci local bus 206 by direct component connection . in contrast , audio adapter 216 , graphics adapter 218 , and audio / video adapter 219 connect to pci local bus 206 by add - in boards inserted into expansion slots . expansion bus interface 214 provides a connection for a keyboard and mouse adapter 220 , modem 222 , and additional memory 224 . scsi host bus adapter 212 connects to hard disk drive 226 , tape drive 228 , and cd - rom drive 230 . an operating system runs on processor 202 and is used to coordinate and provide control of various components within data processing system 200 in fig2 . the operating system may be a commercially available operating system such as windows xp , which is available from microsoft corporation . an object oriented programming system such as java may run in conjunction with the operating system and provides calls to the operating system from java programs or applications executing on data processing system 200 . “ java ” is a trademark of sun microsystems , inc . instructions for the operating system , the object - oriented programming system , and applications or programs are located on storage devices , such as hard disk drive 226 , and may be loaded into main memory 204 for execution by processor 202 . those of ordinary skill in the art will appreciate that the hardware in fig2 may vary depending on the implementation . other internal hardware or peripheral devices , such as flash read - only memory ( rom ), equivalent nonvolatile memory , or optical disk drives and the like , may be used in addition to or in place of the hardware depicted in fig2 . also , the processes of the present invention may be applied to a multiprocessor data processing system . for example , data processing system 200 , if optionally configured as a network computer , may not include scsi host bus adapter 212 , hard disk drive 226 , tape drive 228 , and cd - rom 230 . in that case , the computer , to be properly called a client computer , includes some type of network communication interface , such as lan adapter 210 , modem 222 , or the like . as another example , data processing system 200 may be a stand - alone system configured to be bootable without relying on some type of network communication interface , whether or not data processing system 200 comprises some type of network communication interface . as a further example , data processing system 200 may be a personal digital assistant ( pda ), which is configured with rom and / or flash rom to provide non - volatile memory for storing operating system files and / or user - generated data . the depicted example in fig2 and above - described examples are not meant to imply architectural limitations . for example , data processing system 200 also may be a notebook computer or hand held computer in addition to taking the form of a pda . data processing system 200 also may be a kiosk or a web appliance . the processes of the present invention are performed by processor 202 using computer implemented instructions , which may be located in a memory such as , for example , main memory 204 , memory 224 , or in one or more peripheral devices 226 - 230 . fig3 is a block diagram illustrating the relationship of software components operating within a computer system that may implement the present invention . java - based system 300 contains platform specific operating system 302 that provides hardware and system support to software executing on a specific hardware platform . jvm 304 is one software application that may execute in conjunction with the operating system . jvm 304 provides a java run - time environment with the ability to execute java application or applet 306 , which is a program , servlet , or software component written in the java programming language . the computer system in which jvm 304 operates may be similar to data processing system 200 or computer 100 described above . however , jvm 304 may be implemented in dedicated hardware on a so - called java chip , java - on - silicon , or java processor with an embedded picojava core . at the center of a java run - time environment is the jvm , which supports all aspects of java &# 39 ; s environment , including its architecture , security features , mobility across networks and platform independence . the jvm is a virtual computer , i . e . a computer that is specified abstractly . certain features are present in every jvm , with some range of design choices that may depend upon the platform on which the jvm is designed to execute . for example , all jvms must execute java bytecodes and may use a range of techniques to execute the instructions represented by the bytecodes . a jvm may be implemented completely in software or somewhat in hardware . this flexibility allows different jvms to be designed for mainframe computers and pdas . the jvm is the name of a virtual computer component that actually executes java programs . java programs are not run directly by the central processor but instead by the jvm , which is itself a piece of software running on the processor . the jvm allows java programs to be executed on a different platform as opposed to only the one platform for which the code was compiled . java programs are compiled for the jvm . in this manner , java is able to support applications for many types of data processing systems , which may contain a variety of central processing units and operating systems architectures . to enable a java application to execute on different types of data processing systems , a compiler typically generates an architecture - neutral file format — the compiled code is executable on many processors , given the presence of the java run - time system . the java compiler generates bytecode instructions that are nonspecific to a particular computer architecture . a bytecode is a machine independent code generated by the java compiler and executed by a java interpreter . a java interpreter is part of the jvm that alternately decodes and interprets a bytecode or bytecodes . these bytecode instructions are designed to be easy to interpret on any computer and easily translated on the fly into native machine code . bytecodes are translated into native code by a just - in - time compiler or jit . a jvm loads class files and executes the bytecodes within them . more specifically , a class loader in the jvm loads these class files . the class loader loads class files from an application and the class files from the java application programming interfaces ( apis ), which are needed by the application . the execution engine that executes the bytecodes may vary across platforms and implementations . one type of software - based execution engine is a just - in - time compiler . with this type of execution , the bytecodes of a method are compiled to native machine code upon successful fulfillment of some type of criteria for jitting a method . the native machine code for the method is then cached and reused upon the next invocation of the method . the execution engine may also be implemented in hardware and embedded on a chip so that the java bytecodes are executed natively . jvms usually interpret bytecodes , but jvms may also use other techniques , such as just - in - time compiling , to execute bytecodes . when an application is executed on a jvm that is implemented in software on a platform - specific operating system , a java application may interact with the host operating system by invoking native methods . a java method is written in the java language , compiled to bytecodes , and stored in class files . a native method is written in some other language and compiled to the native machine code of a particular processor . native methods are stored in a dynamically linked library whose exact form is platform specific . fig4 is a block diagram of a jvm in accordance with a preferred embodiment of the present invention . jvm 400 includes class loader subsystem 402 , which is a mechanism for loading types , such as classes and interfaces , given fully qualified names . jvm 400 also contains runtime data areas 404 , execution engine 406 , native method interface 408 , and memory management 410 . execution engine 406 is a mechanism for executing instructions contained in the methods of classes loaded by class loader subsystem 402 . execution engine 406 may be , for example , java interpreter 412 or just - in - time compiler 414 . native method interface 408 allows access to resources in the underlying operating system . native method interface 408 may be , for example , the java native interface ( jni ). runtime data areas 404 contain native method stacks 416 , java stacks 418 , pc registers 420 , method area 422 , and heap 424 . these different data areas represent the organization of memory needed by jvm 400 to execute a program . java stacks 418 store the state of java method invocations . when a new thread is launched , the jvm creates a new java stack for the thread . the jvm performs only two operations directly on java stacks : it pushes and pops frames . a threads java stack stores the state of java method invocations for the thread . the state of a java method invocation includes its local variables , the parameters with which it was invoked , its return value , if any , and intermediate calculations . java stacks are composed of stack frames . a stack frame contains the state of a single java method invocation . when a thread invokes a method , the jvm pushes a new frame onto the java stack of the thread . when the method completes , the jvm pops the frame for that method and discards it . the jvm does not have any registers for holding intermediate values ; any java instruction that requires or produces an intermediate value uses the stack for holding the intermediate values . in this manner , the java instruction set is well - defined for a variety of platform architectures . program counter ( pc ) registers 420 indicate the next instruction to be executed . each instantiated thread gets its own pc register and java stack . if the thread is executing a jvm method , the value of the pc register indicates the next instruction to execute . if the thread is executing a native method , then the contents of the pc register are undefined . native method stacks 416 stores the state of invocations of native methods . the state of native method invocations is stored in an implementation - dependent way in native method stacks , registers , or other implementation - dependent memory areas . in some jvm implementations , native method stacks 416 and java stacks 418 are combined . method area 422 contains class data , while heap 424 contains all instantiated objects . the constant pool is located in method area 422 in these examples . the jvm specification strictly defines data types and operations . most jvms choose to have one method area and one heap , each of which are shared by all threads running inside the jvm , such as jvm 400 . when jvm 400 loads a class file , it parses information about a type from the binary data contained in the class file . jvm 400 places this type of information into the method area . each time a class instance or array is created , the memory for the new object is allocated from heap 424 . jvm 400 includes an instruction that allocates memory space within the memory for heap 424 , but includes no instruction for freeing that space within the memory . memory management 410 in the depicted example manages memory space within the memory allocated to heap 424 . memory management 410 may include a garbage collector , which automatically reclaims memory used by objects that are no longer referenced . additionally , a garbage collector also may move objects to reduce heap fragmentation . the garbage collector performs operations generally referred to as mark / sweep / compact . these operations are the marking of live objects and coalescing sequences of dead objects and spaces that are not marked as live to thereby free or reclaim memory space . any fragmentation caused by the live objects within the heap is compacted during the compact operation . compaction is a process that moves objects toward one end of the heap with the goal of creating the largest possible contiguous free area or areas . compaction helps to avoid allocating new memory to expand the heap size . objects are marked ( noted as live ) by following chains of references from a set of root objects to all other objects they reach . marks are recorded in an area of memory allocated outside of the heap , referred to as a mark bit array . a single bit in the mark bit array is set as each new live object is discovered . the present invention provides an improved method , apparatus , and computer instructions for determining or identifying memory leaks in a heap , such as java heap . the mechanism of the present invention employs an extra bit in the header of each object in the heap . extra bits may be found in most object implementations . after a normal mark - sweep - compact operation cycle , a user driven mark operation sets a bit in the live objects . this bit is used to identify objects that have not been deallocated at the start of the observation period . the user driven mark operation can also be treated as , for example , a periodic event , such as the passage of some period of time in order to constantly monitor the health of the heap . the period of time may be for example , one hour or several days . next fig5 is a diagram illustrating components used to identify leak in a heap in accordance with a preferred embodiment of the present invention . heap 500 in this example is a java heap and may be implemented as heap 424 in fig4 . memory management 502 manages heap 500 and may be implemented as memory management 410 in fig4 . memory management 502 provides management function , including allocating and deallocating objects in heap 500 . additionally , in these illustrative examples , memory management 502 also includes processes for identifying memory leaks in heap 500 . as illustrated in fig5 , heap 500 contains objects 504 , 506 , 508 , and 510 . additionally , indicators 512 , 514 , 516 , and 518 are present in objects 504 , 506 , 508 , and 510 . these indicators take the form of bits in this illustrative example . of course , the indicators may take other forms , such as a flag or a tag that is associated with the object rather than actually being incorporated within the objects . in one illustrative embodiment , all live objects in heap 500 have their indicators set or marked by memory management 502 . in this illustrative example , indicators 512 , 514 , 516 , and 518 are marked by memory management 502 for objects 504 , 506 , 508 , and 510 . the system is then allowed to run in the production environment over the leakage period . this period of time can last for hours , days , or even weeks . no additional overhead is present while the system leaks . when the observation period ends or when a required event occurs , for example , when the heap gets full or near full , an outofmemory exception , a mark - sweep - compact operation is triggered to get the set of actual live objects . then , memory management 502 performs a query of live objects in heap 500 . memory management 502 marks all objects in heap 500 that do not have their indicator marked and presents these to the user in these illustrative examples . these unmarked objects are new objects and the predominant type that are most likely to be a leaked object . this mechanism is useful for memory leaks , which happen over large periods of time . alternatively , the mechanism of the present invention in memory management 502 clears all indicators on currently live objects and then turns on a jvm - wide marking function . the marking operation is triggered on each allocation operation within the jvm and sets the indicator within the created object . this allocation operation may be initiated by an application needed to create an object . when the transaction is over or the observation period has ended , a mark - sweep - compact is triggered to get a set of actual live objects . the presence of marked objects in heap 500 after this step implies the presence of possible memory leaks . a dump of marked objects in heap 500 provides an indication of the source of the memory leak . by identifying objects involved in a memory leak , the processes creating those objects may be determined . as a result , programmers or other designers may alter these processes analyze these processes as part of a memory leak analysis . fig6 is a flowchart of a process for identifying memory leaks in accordance with a preferred embodiment of the present invention . the process illustrated in fig6 may be implemented in a management process , such as memory management 502 in fig5 . the process begins by identifying live objects in a heap ( step 600 ). the identification process is a mark - sweep - compact operation . most jvms have a method to trigger garbage collection programmatically which can be used for the above purpose . the process marks identified live objects through a user driven mark operation ( step 602 ). in these examples , the process marks the objects by setting an indicator , such as a bit in the header of the objects . the system is exposed to the workload , which seems to cause the memory leak . this workload is also referred to as a target workload . thereafter , process observes the system under a target workload ( step 604 ). next , a determination is made as to whether the observation period threshold has been reached ( step 606 ). this threshold may be set in a number of different ways . for example , the threshold may be reached as to when the heap is full or 90 percent full . another possible example is a user - specified end of observation period . if the observation threshold is reached , the process identifies the unmarked objects ( step 608 ). in this illustrative example , the unmarked objects are objects most likely associated with a memory leak in the heap . the process then presents the identified objects ( step 610 ), with the process terminating thereafter . these objects may be presented in a number of different ways . for example , a listing of objects may be presented or a graphical representation of the objects may be displayed in a graphical user interface ( gui ). with reference again to step 606 , if the number of objects do not reach the observation threshold , the process returns to step 604 . next , fig7 is a flowchart of a process for identifying memory leaks in accordance with a preferred embodiment of the present invention . the process illustrated in fig7 may be implemented in a management process , such as memory management 502 in fig5 . the process begins by cleaning the heap ( mark - sweep - compact ) and clearing all live marked objects in the heap ( step 700 ). the process turns on the marking function ( step 702 ). the marking function in step 702 sets the indicator in each new object being allocated hence . the process then waits for the observation period to complete ( step 704 ). the end of the observation period can be denoted by the end of a transaction or user specified time period or a user input . next , a determination is made as to whether any live marked objects are present ( step 706 ). if live marked objects are present , the process dumps the live marked objects ( step 708 ). these live marked objects are objects most likely causing the memory leak . thereafter , the process presents the results of the dump ( step 710 ), with the process terminating thereafter . the process proceeds to step 710 in step 706 , if live marked objects are not present in the heap . in fig8 is a flowchart of a process for a marking function in accordance with a preferred embodiment of the present invention . the process illustrated in fig8 may be implemented in memory management 502 in fig5 in these illustrative examples . the marking function is called by the jvm memory management after allocation of a new object . the process begins by receiving a request to allocate a new object ( step 800 ). the process allocates the object ( step 802 ), and the process marks the object ( step 804 ), with the process terminating thereafter . the setting and resetting of bits or indictors may be preformed using interfaces supported by the jvm . these interfaces include , for example , ones supported by java virtual machine tools interface ( jvmti ). thus , the present invention provides and improved method , apparatus and computer instructions for identifying memory leaks . the mechanism of the present invention employs indicators associated with objects in a heap . these indicators may be contained within the objects or may reference the objects . live objects are identified and the indicators for these live objects are set or unset in the heap depending on the particular implementation . after an event occurs , the heap is examined and objects likely to be associated with a memory leak may be identified through locating marked or unmarked live objects still present in the heap . it is important to note that while the present invention has been described in the context of a fully functioning data processing system , those of ordinary skill in the art will appreciate that the processes of the present invention are capable of being distributed in the form of a computer readable medium of instructions and a variety of forms and that the present invention applies equally regardless of the particular type of signal bearing media actually used to carry out the distribution . examples of computer readable media include recordable - type media , such as a floppy disk , a hard disk drive , a ram , cd - roms , and dvd - roms . the computer readable media may take the form of coded formats that are decoded for actual use in a particular data processing system . the description of the present invention has been presented for purposes of illustration and description , and is not intended to be exhaustive or limited to the invention in the form disclosed . many modifications and variations will be apparent to those of ordinary skill in the art . the embodiment was chosen and described in order to best explain the principles of the invention , the practical application , and to enable others of ordinary skill in the art to understand the invention for various embodiments with various modifications as are suited to the particular use contemplated .	6
in the following detailed description , reference is made to the accompanying drawings , which form a part hereof . in the drawings , similar symbols typically identify similar components , unless context dictates otherwise . the illustrative embodiments described in the detailed description , drawings , and claims are not meant to be limiting . other embodiments may be utilized , and other changes may be made , without departing from the spirit or scope of the subject matter presented herein . the aspects of the present disclosure , as generally described herein , and illustrated in the figures , can be arranged , substituted , combined , separated , and designed in a wide variety of different configurations , all of which are explicitly contemplated herein . some embodiments herein are directed to conveyance assemblies that may include a slide channel and a support channel . each of the slide and support channels may include primary and tertiary support bearings . the primary bearings may be configured to support lateral movement of the slide channel with respect to the support channel . the tertiary support bearings may be configured to provide lateral support between the slide channel and the support channel . sliding or rolling mechanisms in some previous conveyance assemblies did not include lateral support to help to reduce and / or prevent a cargo deck coupled to the rolling mechanism from tilting in a lateral direction relative to the structure that housed the conveyance assemblies . in these and other assemblies , the sliding or rolling mechanisms may be coupled by permanently welding cross - members to secure the desired orientation of the sliding or rolling mechanisms in an installed state . in contrast , in some embodiments of the conveyance assemblies described herein , the tertiary support bearings may provide sufficient lateral support such that cross - members may be eliminated or fixed through a fastener ( e . g ., not welded ) such that a footprint of the conveyance assemblies when disassembled may be smaller than other previous conveyance assemblies . a smaller footprint for a conveyance assembly may reduce storage , shipping , installment , manufacturing , and other costs , along with providing other benefits . fig1 a - 1c illustrate top , side , and cross - sectional views of an example support channel 10 , arranged in accordance with at least one embodiment described herein . the support channel 10 may be defined by first , second , and third sides 11 , 12 , 13 . the second and third sides 12 , 13 may extend orthogonally from the first side 11 , such that the support channel 10 may be substantially rectangular . a first flange 14 a may extend from the second side 12 , away from the third side 13 . a second flange 14 b may extend from the third side 13 , away from the second side 12 . the support channel 10 may include first , second , and third fastener tabs 18 a , 18 b , and 18 c , referred to herein as “ fastener tabs 18 ,” coupled to the first side 11 . the fastener tabs 18 may be configured to receive fasteners to couple the fastener tabs 18 with support cross - members to facilitate the assembly of a support frame , described in further detail below . the support channel 10 may include a primary support bearing 15 operably coupled to the second and third sides 12 , 13 of the support channel 10 . the support channel 10 may include a tertiary support bearing 17 operably coupled to the third fastener tab 18 c . the tertiary support bearing 17 may extend through openings 11 o , 12 o defined , respectively , along the first side 11 and the second side 12 . the primary and tertiary support bearings 15 , 17 may be configured to contact , respectively , a first side 21 and a first flange 24 a of a slide channel 20 ( fig2 a - 2c ), described in further detail below . the support channel 10 may also include a catch member 19 configured to engage with a stop member 29 of the slide channel 20 ( fig2 a - 2c ) to help to reduce and / or prevent overextension of the slide channel 20 with respect to the support channel 10 , described in further detail below . the support channel 10 may be formed from any type or a combination of types of materials . in some embodiments , the support channel 10 may be formed from steel . in particular , the support channel 10 may be formed by roll - forming steel . fig2 a - 2c illustrate bottom , side , and cross - sectional views of the slide channel 20 , arranged in accordance with at least one embodiment described herein . the slide channel 20 may include a first side 21 , a second side 22 , and a third side 23 . the second and third sides 22 , 23 may extend orthogonally from the first side 21 , such that the slide channel 20 may be substantially rectangular . a first flange 24 a may extend from the second side 22 toward the third side 23 . a second flange 24 b may extend from the third side 23 toward the second side 22 . the slide channel 20 may include a primary slide bearing 25 operably coupled to the first side 21 of the slide channel 20 . the slide channel 20 may include first and second secondary slide bearings 26 a , 26 b , referred to herein as “ secondary slide bearings 26 ,” operably coupled to the second and third sides 22 , 23 , respectively , of the slide channel 20 . the slide channel 20 may also include a tertiary slide bearing 27 operably coupled to the third side 23 of the slide channel 20 . the primary slide bearing 25 may be configured to contact the first side 11 of the support channel 10 . the secondary slide bearings 26 may be configured to contact the first and second flanges 14 a , 14 b of the support channel 10 . the tertiary slide bearing 27 may be configured to contact the third side 13 of the support channel 10 . the slide channel 20 may further include a stop member 29 , disposed along the first side 21 . the stop member 29 may be configured to contact the catch member 19 of the support channel 10 to help to reduce and / or prevent overextension of the slide channel 20 with respect to the support channel 10 , described in further detail below . the slide channel 20 may be formed from any type or a combination of types of materials . in some embodiments , the slide channel 20 may be formed from steel . in particular , the slide channel 20 may be formed by roll - forming steel . fig3 a and 3b illustrate cross - sectional views of the support channel 10 of fig1 a - 1c and the slide channel 20 of fig2 a - 2c in an assembled state , arranged in accordance with at least one embodiment described herein . more particularly , fig3 a illustrates the interactions of the primary and tertiary support bearings 15 , 17 with the slide channel 20 . fig3 b illustrates the interactions of the primary , secondary , and tertiary slide bearings 25 , 26 , 27 with the support channel 10 . in the assembled state , the primary and tertiary support bearing 15 , 17 and the primary , secondary , and tertiary slide bearings 25 , 26 , 27 may be located at opposite ends of , respectively , the support and slide channels 10 , 20 . accordingly , the cross - sectional views of fig3 a and 3b may illustrate opposite ends of the support and slide channels 10 , 20 in the assembled state . in the assembled state , the support channel 10 may be at least partially enclosed by the slide channel 20 , the respective second sides 12 , 22 , and the third sides 13 , 23 of the support and slide channels 10 , 20 may be adjacent to one another , and the first and second flanges 24 a , 24 b of the slide channel 20 may overlap with the first and second flanges 14 a , 14 b of the support channel 10 . the first and second flanges 14 a , 14 b of the support channel 10 may extend orthogonally to define a width equal to approximately the length of the first side 21 of the slide channel 20 . the first and second flanges 24 a , 24 b of the slide channel 20 may extend orthogonally to define a space equal to approximately the length of the first side 11 of the support channel 10 . accordingly , longitudinal movement of the slide channel 20 with respect to the support channel 10 may be substantially restricted by the respective flanges 14 a , 14 b , 24 a , 24 b . referencing fig3 a , the primary support bearing 15 may contact the first side 21 of the slide channel 20 to facilitate longitudinal movement of the slide channel 20 with respect to the support channel 10 . the tertiary support bearing 17 may contact the first flange 24 a of the slide channel 20 to help to reduce and / or prevent lateral movement of the slide channel 20 with respect to the support channel 10 . referencing fig3 b , the primary slide bearing 25 may contact the first side 11 of the support channel 10 to facilitate longitudinal movement of the slide channel 20 with respect to the support channel 10 . the secondary slide bearings 26 may contact the first and second flanges 14 a , 14 b of the support channel 10 to further facilitate longitudinal movement of the slide channel 20 with respect to the support channel 10 and to help to reduce and / or prevent accidental or other disassembly of the slide channel 20 from the support channel 10 . the tertiary slide bearing 27 may contact the third side 13 of the support channel 10 to help to reduce and / or prevent lateral movement of the slide channel 20 with respect to the support channel 10 . in the example embodiment , the roll - formed manufacture of the support and slide channels 10 , 20 may allow for smoother longitudinal transition of the slide channel 20 with respect to the support channel 10 . for example , the roll - formed manufacture may reduce or eliminate mil that may form in the slide channel 20 when the slide channel 20 is manufactured using other methods . the substantially rectangular shapes of the support and slide channels 10 , 20 may facilitate smooth contact between the support and slide bearings 15 , 17 , 25 , 26 , 27 and the support and slide channels 10 , 20 , further promoting smooth translation of the slide channel 20 with respect to the support channel 10 and thereby reducing wear on the support or slide bearings 15 , 17 , 25 , 26 , 27 . alternately or additionally , the stop member 29 may contact the catch member 19 as the slide channel 20 slides along the support channel 10 to help to reduce and / or prevent overextension and / or accidental disassembly . modifications , additions , or omissions may be made to the support channel 10 illustrated in fig1 a - 1c and the slide channel 20 illustrated in fig2 a - 2c without departing from the scope of the present disclosure . the proportions and dimensions of the support channel 10 and / or slide channel 20 may vary . accordingly , the dimensions or locations of the support or slide bearings 15 , 17 , 25 , 26 , 27 may vary . furthermore , the number of support or slide bearings 15 , 17 , 25 , 26 , 27 provided on the support and slide channels 10 , 20 may vary . in these and other embodiments , the catch and stop members 19 , 29 may be removable to allow disassembly of the slide channel 20 from the support channel 10 . fig4 illustrates a top view of an example support frame 200 , arranged in accordance with at least one embodiment described herein . the support frame 200 may include first and second support channels 110 a and 110 b , referred to herein as “ support channel ( s ) 110 .” the support channels 110 may substantially embody the support channel 10 described according to fig1 a - 1c . the support frame 200 may further include first , second , and third support cross - members 130 a , 130 b , 130 c , referred to herein as “ support cross - member ( s ) 130 .” the first support cross - member 130 a may be coupled to the first and second support channels 110 a , 110 b at the respective first fastener tabs 18 a . the second support cross - member 130 b may be coupled to the respective second fastener tabs 18 b of the first and second support channels 110 a , 110 b . the third support cross - member 130 c may be coupled to the first and second support channels 110 a , 110 b at the respective third fastener tabs 18 c . the support cross - members 130 may be configured to receive fasteners to facilitate fixation of the support frame 200 to a structure , such as a cargo space inside of a vehicle or other storage space . in other embodiments , the support cross - members 130 may couple to the support channels 110 using other fastener devices . in these and other embodiments , the support cross - members 130 may not be welded to the support channels 110 . fig5 illustrates a bottom view of an example slide frame 300 , arranged in accordance with at least one embodiment described herein . the slide frame 300 may include first and second slide channels 120 a and 120 b , referred to herein as “ slide channel ( s ) 120 .” the slide channels 120 may substantially embody the slide channel 20 described according to fig2 a - 2c . each of the first and second slide channels 120 a , 120 b may include first , second , and third fastener tabs 28 a , 28 b , 28 c , referred to herein as “ fastener tab ( s ) 28 ,” coupled to the second or third side 22 , 23 . the slide frame 300 may further include first , second , third , and fourth slide cross - members 140 a , 140 b , 140 c , 140 d referred to herein as “ slide cross - member ( s ) 140 .” the first slide cross - member 140 a may be coupled to the first and second slide channels 120 a , 120 b at the respective first fastener tabs 28 a . the second slide cross - member 140 b may be coupled to the first and second slide channels 120 a , 120 b at the respective second fastener tabs 28 b . the third slide cross - member 140 c may be coupled to the first and second slide channels 120 a , 120 b at the respective third fastener tabs 28 c . the fourth slide cross - member 140 d may be coupled to the first and second slide channels 120 a , 120 b at the respective proximal ends . the slide cross - members 140 may be configured to receive fasteners to facilitate fixation of an apparatus , such as a container , drawer , or shelf , to the slide frame 300 . in other embodiments , the slide cross - members 140 may couple to the slide channels 120 using other fastener devices . in these and other embodiments , the slide cross - members 140 may not be welded to the slide channels 120 . the slide frame 300 may be configured to support a latch mechanism , described in further detail below . as illustrated in fig6 a - 6d , the slide frame 300 may slidably engage with the support frame 200 to form a slidable conveyance assembly 100 ( referred to herein as the “ assembly 100 ”). the support frame 200 may be configured to be fixed to a structure , such as a cargo space inside of a vehicle or other storage space . the slide frame 300 may be configured to slide with respect to the support frame 200 in a longitudinal direction relative to the cargo space . furthermore , the slide frame 300 may be configured to support any apparatus , such as a container , drawer , and / or a shelf . the apparatus supported thereon may therefore be transitioned in and out of the structure by transitioning the slide frame 300 . the slide channels 120 of the slide frame 300 may be slidably engaged with the support channels 110 of the support frame 200 in an assembled state that substantially embodies the slidable engagement of the assembled state of the slide channel 20 with the support channel 10 described according to fig3 a and 3b . accordingly , the slide channels 120 may slide with respect to the support channels 110 by way of the primary and tertiary support bearings against the slide channels 120 and the primary , secondary , and tertiary slide bearings against the support channels 110 . the first slide channel 120 a may slide with respect to the first support channel 110 a and the second slide channel 120 b may slide with respect to the second support channel 110 b . as a result , the slide frame 300 may slidably transition in a longitudinal direction along the support frame 200 between an unextended state ( fig6 a and 6b ) and an extended state ( fig6 c and 6d ), with little to no lateral movement relative to the support frame 200 . the assembly 100 may further include a latch mechanism 150 . the latch mechanism 150 may include a first latch member 151 having first , second , and third corners 151 a , 151 b , 151 c , a second latch member 152 having first and second ends 152 a , 152 b , a latch rod 153 having first and second ends 153 a , 153 b , and a latch handle 154 at the first end 153 a of the latch rod 153 . the first corner 151 a may be rotatably engaged with a first tab 155 a disposed on the first slide cross - member 140 a . the second corner 151 b may be rotatably engaged with a second tab 155 b disposed on the second end 153 b of the latch rod 153 . the third corner 151 c may be rotatably engaged with the first end 152 a of the second latch member 152 . the latch rod 153 may be manipulated by the latch handle 154 to transition the latch mechanism 150 between an engaged state and an unengaged state . in the engaged state , the second latch member 152 may transition laterally towards the first slide channel 120 a ; in the unengaged state , the second latch member 152 may transition laterally away from the first slide channel 120 a . the latch mechanism 150 may be configured to secure the slide frame 300 with respect to the support frame 200 such that slidable movement of the slide frame 300 with respect to the support frame 200 is restricted at certain points . in some embodiments , the first slide channel 120 a may include a first slot configured to receive the second end 152 b of the second latch member 152 . the first support channel 110 a may include one or more slots configured to align with the first slot of the first slide channel 120 a as the slide frame 300 slides with respect to the support frame 200 . accordingly , at certain points along the slidable transition of the slide frame 300 , the first slot of the first slide channel 120 a may align with one of the one or more slots of the first support channel 110 a , whereupon the latch mechanism 150 may be transitioned into the engaged state , such that the second latch member 152 extends through the slots of both the first support and slide channels 110 a , 120 a , thereby securing the slide frame 300 with respect to the support frame 200 . modifications , additions , or omissions may be made to the assembly 100 illustrated in fig4 - 6d without departing from the scope of the present disclosure . in some embodiments , the support and slide frames 200 , 300 may include fewer or more support and slide cross - members 130 , 140 , respectively , than those illustrated . alternately or additionally , the support and slide cross - members 130 , 140 may be disposed along the support and slide channels 110 , 120 at different locations than those illustrated . in other embodiments , the assembly 100 may not include any support or slide cross - members 130 , 140 . in these and other embodiments , an apparatus supported by the assembly 100 , such as a drawer or shelf , may be coupled to both first and second slide channels 120 a , 120 b of the slide frame 300 such that the first and second slide channels 120 a , 120 b slide along the first and second support channels 110 a , 110 b in unison . alternately or additionally , in some embodiments , the assembly 100 may not include the latch mechanism 150 , or may include more than one latch mechanism 150 , or may include a different type of latch mechanism 150 than that discussed and / or illustrated above . alternately or additionally , the assembly 100 may include fewer or more support and slide channels 110 , 120 . for example , in some embodiments , the assembly 100 may include a single support channel 110 and a single slide channel 120 . alternately or additionally , the assembly 100 may include three or more support channels 110 and a corresponding slide channel 120 for each support channel 110 provided . in these and other embodiments , the number of support and slide channels 110 , 120 provided may vary based on the required width of the assembly 100 , the apparatus supported by the assembly 100 , and / or the weight of the cargo to be supported by the assembly 100 , among other factors . from the foregoing , it will be appreciated that various embodiments of the present disclosure have been described herein for purposes of illustration , and that various modifications may be made without departing from the scope and spirit of the present disclosure . accordingly , the various embodiments disclosed herein are not intended to be limiting , with the true scope and spirit being indicated by the following claims .	1
symbols ( reference numerals ) mainly used in the figures indicate the following : 101 denotes signal input ; 102 addition of parity ; 103 addition of subcode ; 104 interleave ; 105 modulation ; 106 a disk ; 107 system control ; 109 a semiconductor circuit for processing recording signals ; 110 output ; 111 a process of putting data together in predetermined units ; 112 error correction ; 113 address detection ; 114 deinterleave ; 115 demodulation ; and 119 a semiconductor circuit for processing reproducing signals . a preferred embodiment of the present invention will be described below with reference to the accompanying drawings . fig2 and 3 show data structures used to record user data according to the present invention . fig1 shows an example in which the size of a record block is changed according to the present invention . fig4 shows a data arrangement obtained as a result of rearranging the data structure shown in fig3 to actually record the data . fig2 shows a data structure of a record unit of data to be recorded on a recording medium according to the present invention . the following description assumes that the recording medium is an optical disk . the record block comprises : in each column , 496 bytes ; and in each row , a sync ( synchronization signal ) of one byte , data of 38 bytes , and 3 sets of a burst error detecting subcode of one byte and data of 38 bytes ; totaling 77 , 736 bytes . the arrow indicates the direction in which data is recorded on a disk . the ldc ( long distance code ) portions constitute user data and are obtained as a result of adding 32 parities to 216 pieces of data , using an rs ( reed solomon ) code . in the figure , the code runs sequentially as a single column indicated by the shaded portion . however , the code may be divided and arranged by means of interleaving . fig3 shows a data arrangement in which each 2k bytes of data is put together into one logical block using the record block shown in fig2 . thus , 32 2k - byte logical blocks can be arranged using the 64k - byte record block . in addition to the above example , the logical blocks may be arranged such that each 2 blocks are aligned in a row . fig4 shows the structure of data obtained as a result of adding error correcting code to the 2k - byte logical blocks 1 to 4 shown in fig3 . as shown in the figure , the error correcting code rs ( 248 , 216 , 31 ) is vertically ( in the column direction ) added to the data . thus , the figure shows a case in which the error correcting code is added to the vertically aligned logical blocks 1 to 4 . however , the error correcting code may be added to the logical blocks 1 , 16 , 2 , and 17 with the same effect . thus , the present invention is not limited to a specific combination of logical blocks ; any combination may be employed by means of regular interleaving . fig1 shows a method for forming and recording a record block smaller than that shown above . as shown in fig2 , the record block a comprises : in each column , 496 bytes ; and in each row , a sync of one byte , data of 38 bytes , and 3 sets of a burst error detecting subcode of one byte and data of 38 bytes ; totaling 77 , 736 bytes . the arrow indicates the direction in which the data is recorded on a disk . the record block b 1 comprises : in each column , 62 bytes ; and in each row , a sync of one byte , data of 38 bytes , and 3 sets of a burst error detecting subcode of one byte and data of 38 bytes , as in the case of the record block a ; totaling 9 , 672 bytes . the direction in which data is recorded on a disk is the same as that for the record block a . data of 2048 bytes and an error check code of 4 bytes collectively form a recorded data unit , and the data of the record block a is made up of 32 recorded data units . as for the record block b 1 , data of 2048 * 4 bytes and an error check code of 4 * 4 bytes collectively form its minimum recorded data unit . the minimum recorded data unit is rearranged , as indicated by the record block b 2 in the figure , to form a structure ( arrangement ) similar to that of the record block a which includes rs code ( error correcting code ), making it possible to use the same method as that employed for the record block a for carrying out ram control to temporarily store data for signal processing or performing error correction processing . that is , error correcting code and then a subcode are added to the structure of the record block b 2 . when recording the data , the data is recorded as the record block b 1 ( using the structure of the record block b 1 ). since the subcode is a code string of 62 bytes , it may be added as a single column or arranged by means of interleaving . incidentally , data of 2048 bytes are roughly 2k bytes . accordingly , the record block b 1 has a data structure for recording 8k bytes of data which includes 62 record block units each arranged in a row . however , the record block b 1 is not limited to this specific data structure , that is , this specific number of bytes , 8k bytes . the record block b 1 ( that is , its data structure ) may be of any size if it can be easily divided and rearranged to form the data structure of the record block a . on the other hand , a data structure made up of small blocks such as those described above may make it impossible to interleave the data , deteriorating the error correction capability . to solve this problem , the same data may be recorded a plurality of times or error correcting parities may be added . fig7 shows a 16k - byte recorded data structure formed from the 8k - byte recorded data structure shown in fig1 . a 32k - byte recorded data structure also can be easily obtained from the 16k - byte recorded data structure using a similar method . fig8 shows an area in the user data area of a dvd in which copy control information is recorded . in the figure , the area cgms ( copy generation management system ) records information on user data , and therefore is not required as management information data . accordingly , management information may be recorded in this area by coding the size of data to be recorded into a few types of code and recording the code . for example , when 2 bits are assigned to the area cgm , the flag “ 00 ” may be used to indicate an 8k byte recorded data . the area for recording such information is not limited to the area cgms . any area can be used to record such information if it is used for user data and not included in the management area . fig8 shows a data structure larger than that shown above . as shown in fig8 , the record block d comprises 32k bytes of data , which is half of the 64k - byte record block a in size . since dvds record data in units of 32k bytes , a record block of this data size can easily be made compatible with a dvd system . with this record block , data to be recorded is added with parities and subcodes and then interleaved such that the data is distributed to enhance the burst error detecting capability . the subcodes may be added after the interleave instead of before the interleave . with the record block a , data is interleaved by adding parities to the data and then , for example , rearranging it . with this arrangement using an interleaving technique , when a burst error has occurred , two apparent burst errors half as long as the actual burst error are detected . therefore , even in the case where data cannot be serially reproduced due to the burst error , the data may be corrected by use of the added parities if the apparent burst errors are within a distance of error correction by use of interleaving . to obtain such effect , the data is interleaved and then the subcodes added to the interleaved data are also interleaved to enhance the error correction capability . since the record block d includes data smaller than that of the record block a , the same interleaving technique as that for the record block a cannot be applied to the record block d . accordingly , the subcodes are interleaved within 248 bytes . by using such a method , it is possible to form and record a record block of 32k bytes . in each of the above descriptions , data is put together in units of a number of bytes close to the nth power of 2 ( n is an integer ). this is not restrictive . to round a fraction , redundant data may be added to produce a number easy to use when combining data . fig9 shows an example of how data to be recorded according to the present invention is actually recorded on a disk . the recording disk has arranged thereon a management information area , a read - in area , a user data area , and a readout area , and data is recorded in a predetermined format in each area . data is recorded in predetermined record blocks having 64k bytes in the user data area . as for the management information area , data is recorded in record blocks having a block size smaller than 64k bytes , namely 4k bytes , 8k bytes , 16k bytes , or 32k bytes . by recording data as described above , it is possible to efficiently record management information in a limited area . it should be noted that even though the management area is provided inside the read - in area in fig9 , this relationship may be reversed . furthermore , if it is known beforehand that there is not enough management area , it may be arranged such that a definition can be established to extend it . for example , the border between the read - in area and the user data area shown in fig5 may not be fixed ( even though it is fixed between 02ffffh and 030000h in terms of ecc block addresses in the figure ), and may be changed . in such a case , the position of the changed border can be recorded in the first portion of a specific area such as the management information area to extend the management area if it is known beforehand that a management area of large size is required . fig1 shows a configuration of a recording apparatus according to the present invention . reference numeral 101 denotes a signal input section for inputting data to be recorded ; 102 an “ addition of parity ” section for adding error correcting code ; 103 an “ addition of subcode ” section for adding information such as addresses in a distributed manner ; 104 an interleave section for rearranging data ; 105 a modulation section for recording data ; and 106 a disk on which the data is recorded . reference numeral 107 denotes a system control circuit for controlling the system , while 109 denotes a semiconductor circuit for processing recording signals . though not shown , a recording means is provided to record data on a recording medium . the term “ a recording means ” here denotes , for example , an optical head . a recording means may further include a recording optical system and a laser for recording . the term “ a combining means ” here indicates a means for putting together data to be recorded on a recording medium in predetermined units so that parities can be added to the data . for example , the process ( section ) 100 for combining data into predetermined units shown in fig1 is a combining means . it should be noted that if there are a plurality of different data units ( that is , each data unit consists of a different number of bytes , etc .) in which data is put together , a different circuit may be used for each data unit , or alternatively a single circuit may be used which is capable of changing the number ( of bytes ) constituting the data unit . further , an error correcting code adding means is a means for adding parities to data to be recorded on a recording medium . for example , the “ addition of parity ” section 102 shown in fig1 is an error correcting code adding means . an error correction code adding means may include a mechanism for storing data in a ram , etc . and writing / reading the data . it should be noted that if there are a plurality of different data units ( that is , each data unit consists of a different number of bytes , etc .) in which data is put together , a different circuit may be used for each data unit as an error correcting code adding means , or alternatively a single circuit may be used for all different data units as an error correcting code adding means by switching among different data units or among different data string units ( each having a different number of bytes , etc .). the system is controlled such that when data to be recorded is management information and small , each piece of data entered from the signal input section is set to be small and is not subjected to ordinary interleave processing but directly subjected to modulation and recorded on a disk by use of changeover switches after it is added with parities and subcodes . in the figure , the addition of subcode 103 is carried out before the interleave . however , it may be carried out after the interleave , depending on the data to be recorded . furthermore , even in the above case in which data is not subjected to the ordinary interleave processing by use of the changeover switches , the data may be subjected to simple interleave processing which is suitable for small data to be recorded . the above processing operations may be switched by a changeover signal from the system control 107 or automatically switched by means of address detection performed inside the semiconductor circuit 109 . fig1 shows a configuration of a reproducing circuit ( apparatus ). a reproduced signal from a disk 106 is demodulated by a demodulation section ( circuit ) 115 and is subjected to address detection by an address detection section 113 . reference numeral 114 denotes a deinterleave section for rearranging data . the data is subjected to error correction by an error correction section 112 , and output from a terminal 111 after the data is put together in predetermined units . reference numeral 119 denotes a semiconductor circuit for processing reproducing signals . the term “ a demodulating means ” here denotes a means for demodulating data in a recording medium . for example , the demodulation circuit 115 in fig1 is a demodulating means . the term “ a reproduction combining means ” here indicates a means for combining data reproduced from a recording medium in predetermined units corresponding to units in which the data was recorded , in order to carry out error correction . this means corresponds to the process ( address detection section ) 113 , shown in fig1 , for detecting the address of data and combining the data in predetermined units . it should be noted that if there are a plurality of different data units ( that is , each data unit consists of a different number of bytes , etc .) in which data is put together , a different circuit may be used for each data unit , or alternatively a single circuit may be used which is capable of changing the number ( of bytes ) constituting the error correction data unit based on the address value . further , an error correcting means is a means for correcting an error in data reproduced from a recording medium . for example , the error correction section 112 shown in fig1 is an error correcting means . an error correcting means may include a mechanism for storing data in a ram , etc . and writing / reading the data . it should be noted that if there are a plurality of different data units ( that is , each data unit consists of a different number of bytes , etc .) in which data is put together , a different circuit may be used for each data unit as an error correcting means , or alternatively a single circuit may be used for all different data units as an error correcting means by switching among different data units or among different data string units ( each having a different number of bytes , etc .). the system is controlled such that when data to be reproduced is management information and small , the unit of data to be reproduced from a recording medium and error - corrected is set to be small and subjected to error correction . when management information data of small size is read out , the location of the data is checked by means of address detection . by controlling changeover switches , the data is not subjected to the ordinary interleave processing before it is stored . then , the data is error - corrected in predetermined record blocks and output . fig1 shows the structure of cpr_mai ( copyright management information ) 403 in the data area in a dvd . of available 48 bits , only 4 bits are currently used . reference numeral b 47 denotes cpm ( copyrighted material ) which indicates whether this sector includes a copyrighted material ; b 46 denotes cp_sec which indicates whether this sector has a specific data structure for a copyright protection system ; and b 45 and b 44 denote cgms ( copy generation management system ) which records copy restriction information . information on control of data copying must be recorded in the data area . however , copy information such as cgms need not be recorded in the management area . accordingly , the following arrangement can be made . the size of a record block in the management area may be coded into a code of 2 bits which is then recorded in the cgms 2 - bit area , making it possible to obtain the size of the record block . fig1 shows a data structure used to record data in units of 4k bytes . in the figure , reference numerals a to h each denote a data unit having 19 bytes in each row and 31 bytes in each column . a record block e 2 comprises : two subcode strings each having 62 bytes including parities ; and 19 code strings each having 248 bytes arranged in a column . these data units ( the record block e 2 ) are rearranged into a record block e 1 having a data structure comprising 31 bytes in each column and 156 bytes in each row . by using such a data structure , it is possible to record data having a size of 4k bytes . incidentally , if the subcode strings s 1 and s 2 in the record block e 2 are divided and rearranged as they are , the positions of the syncs after the rearrangement do not match the arrangement of the user data in the record block e 1 . to solve this problem , as shown in fig1 , the syncs are inserted into specific portions in the structure of the code strings s 1 and s 2 , and data , such as address information , and parities added to the data are put in the other portions . by using such a data structure of the subcodes , it is possible to match the positions of the syncs with the arrangement of the user data . fig1 shows an example in which errors are included in portions of a sync and a subcode when the 4k - byte data structure illustrated in fig1 and 14 is reproduced . in the figure , a sync n . g . and a subcode n . g . are indicated as error examples . specifically , when a sync is not properly detected or erroneous data is included in error correcting code for subcode , the subsequent string must be processed since the string may be erroneous . when a sync detection n . g . or a subcode n . g . occurs , as described above , the error portions included in the data units a to h can be estimated from the position of the sync n . g . or the subcode n . g . as indicated by the shaded portions in the figure . by correcting errors in data based on this information , it is possible to properly decode the data . in such a case , the data may be recorded a plurality of times . fig1 shows another example ( different from the example of fig1 ) in which the case where a sync is not properly detected or erroneous data is included in error correcting code for subcode occurs a plurality of times serially , and the data between the errors is processed since the data may be erroneous . use of such an algorithm increases the reliability of information on the positions of errors in data , making it possible to correct the data by discarding the erroneous portions . fig1 is a flowchart showing a method for processing the data to be recorded described so far , changing the structure of the data . first of all , when data is recorded , it is determined whether the target area is the management area at step 171 , and if it is the user data area , the data is processed in units of 64k bytes . syncs and subcodes are added at step 173 , and the data is interleaved to produce a record data structure at step 174 . if the target area is determined to be the management area at step 171 , on the other hand , the size of the data to be recorded is determined at step 175 . in this case , if the size of the data to be recorded requires that the data be recorded in record units of 64k bytes , a 64k - byte record block is used to record the data as in the case of the user data area . the sizes which require that data be recorded in record units of 64k bytes include sizes a little smaller than 64k bytes ( for example , 60k bytes or so ) and sizes larger than 64k bytes . if the size of the data to be recorded is determined to be small at step 175 , an appropriate record block size is selected based on the size of the data to be recorded at step 179 . as described above , a record block can be configured such that its size is set to be one of various sizes smaller than 64k bytes , such as 32k bytes ( illustrated in fig8 ), 16k bytes ( illustrated in fig7 ), 8k bytes ( illustrated in fig1 ), and 4k bytes ( illustrated in fig1 ). accordingly , by selecting an appropriate record block size based on the size of data to be recorded , it is possible to reduce an amount of data recorded in the management area . then , an identification code is added at step 180 . the identification code indicates the size of a record block . the addition of syncs and subcodes and the conversion of the data arrangement are carried out based on the size of the record block indicated by this identification code . specifically , at step 181 , the data to be recorded and the identification code are added with syncs and subcodes for small sizes . at step 182 , the data is rearranged based on the size to produce data to be recorded . by carrying out such processing , it is possible to record even data of small size in a disk management area . according to the present invention described above , when data is recorded on a recording medium , even data of small size to be recorded can be subjected to recording signal processing in much the same way as ordinary data ( of ordinary size ) to be recorded , making it possible to record data in a management information area in small units . accordingly , it is possible to reduce the time required for recording management information , and efficiently use the management information area .	6
the apparatus and methods of the present invention may be employed in particular to improve the detection of an analyte that may be present in a variety of fluids . gases are the preferred fluids according to the practice of the present invention , and therefore the following description of the invention will include a description of the arrangement , construction , and operation of pneumatic devices , and is directed to the control of a plurality of gaseous streams in a detector in a gas chromatographic analytical system ( hereinafter , a chromatograph ). however , for the purposes of the following description , the term &# 34 ; pneumatic &# 34 ; will also be considered to refer to all types of fluids . further examples that are particularly benefited by use of the present invention include supercritical fluid chromatography and high - pressure gas chromatography ( hpgc ). however , it should be understood that the teachings herein are applicable to other analytical instruments , including liquid chromatographs , high - pressure liquid chromatographs ( hplc ), clinical analyzers , flow - injection analyzers , laboratory water purification systems , syringe - type reagent dispensers , manual and automated solid phase extraction ( spe ) instruments , supercritical fluid extraction ( scf ) instruments , stopped - flow spectrophotometers , automated protein or nucleic acid sequencers , and solid phase protein or nucleic acid synthesizers . a new and novel analytical instrument is shown in fig1 and is generally designated chromatograph 10 . in the preferred embodiment , the chromatograph 10 is a hewlett - packard hp6890 gas chromatograph . in order to perform a chromatographic separation of a given sample compound , a sample is injected with a pressurized carrier gas by means of an injector 12 . the carrier gas supplied to injector 12 is provided from a source 12a through one or more pneumatic manifold assemblies 13 , each of which serves in part to control and redirect a plurality of gas flows , including the carrier gas and a plurality of detector gasses of appropriate types , such as air , hydrogen , and make - up gas . the detector gases are provided from respective sources ( one such source 24a is shown ) to the pneumatic manifold assembly 13 . suitable fluid - handling devices such as valves , sensors and the like in the pneumatic manifold assembly 13 are operated under the control of the computer 22 by a way of control signals provided on a data and control lines 28 , 30 . for example , the pneumatic controller 26 effects control of , among other things , fluid flow rate , fluid pressure , fluid flow regulation , and the continuity or discontinuity of flow . as further example , the time during which a particular valve in the pneumatic manifold assembly 13 will remain open and closed in relation to control signals received on the data and control line 28 and in accordance with certain operating conditions of the chromatograph 10 . the control and data line 30 also allows the return of sense information from suitable sensors and signal - interface electronics that are provided in the pneumatic manifold assembly 13 . accordingly , the computer 22 , pneumatic controller 26 , and pneumatic manifold 13 may be operated to effect a modulation of any of the aforementioned gas flows , either individually or in combination . a column 14 is positioned within an oven 16 . the carrier gas / sample combination passing through column 14 is exposed to a temperature profile resulting in part from the operation of a heater 18 within oven 16 . during this profile of changing temperatures , the sample will separate into its components primarily due to differences in the interaction of each component with the column 14 at a given temperature . as the separated components exit the column 14 , they are detected by the detector 24 . as the components exit column 14 they are detected by a flame - based detector ( hereinafter , detector ) 24 . in particular , and in accordance with a feature of the present invention , the pneumatic controller 26 modulates the flow of one or more of the detector gases that are provided to the detector 24 during an ignition sequence , as will be described below . computer 22 maintains overall control of all systems associated with gas chromatograph 10 . it will be recognized that any particular gas chromatograph may include more systems than those described in relation to the present invention . it will also be understood that although computer 22 is shown as a single block , such computer includes a central processing unit and all associated peripheral devices , such as random access memories , read - only memories , input / output isolation devices , clocks and other related electronic components . in the preferred embodiment , the central processor used in computer 22 is a microprocessor . as such , computer 22 includes a memory in which information and programming can be stored and retrieved by known methods . however , it will be appreciated that the programmed control of pneumatic controller 26 can be implemented by other computing means , such as an embedded microprocessor or dedicated controller circuit incorporated in the pneumatic controller 26 . also , the programming associated with computer 22 that is utilized in relation to the present invention will be readily understood from the description herein . an electronic control panel 50 is shown to include at least two main input / output components , namely a keypad 58 , and a display 60 . by monitoring the operation of the chromatograph 10 by signals from certain components , such as the detector 24 , the computer 22 can initiate and maintain certain functions required for an analytical run . consequently , indicating or prompt messages can be generated by computer 22 and displayed on display 60 . operating commands and other information are entered into computer 22 by way of keypad 58 . one particular data type is detector ignition setpoint values and one particular operating command is a detector ignition command , both of which may be prompted by messages displayed on display 60 and the requisite command or data are entered through keypad 58 . another particular type of data is a detector ignition lit offset value , which may be acknowledge by messages displayed on display 60 and modified by commands and data entered through keypad 58 . the ensuing ignition sequence which relates to the present invention is then automatically provided under control of the computer 22 as described below in reference to fig4 and 5 . the control of one or more fluid flow characteristics is provided as shown in fig2 and 3 . in the embodiments illustrated in fig2 and 3 , the computer 22 controls the flow of the make - up fluid , the first fluid , the first detector fluid , and the second detector fluid by transmitting an appropriate signal to the pneumatic controller 26 , which in turn provides respective signals to a respective valve in the pneumatic manifold assembly 13 to increase or decrease the amount of fluid flowing therethrough to the detector 201 . in particular , the fluid flow control in the embodiment illustrated in fig3 is preferably provided via electronic pneumatic control ( epc ). for further details of electronic pneumatic control techniques , one may consult , for example , klein , et al ., u . s . pat . nos . 4 , 994 , 096 and 5 , 108 , 466 , the disclosures of which are incorporated herein by reference . fig2 shows a schematic illustration of a first preferred embodiment of a detector 201 preferably constructed as a fid and a pneumatic control section 202 that is best suited for operation in a non - epc configuration . the detector 201 constructed to include an igniter 211 , an ignition line 212 , and a collector electrode 213 . the igniter 211 and the collector electrode 213 are aligned in the interior of a jet 214 that is mounted in a passageway defined by a fluid - directing structure 210 . an electronic power supply ( not shown ) provides a controlled amount of electrical current or voltage on the ignition line 212 to cause a selectable amount of heat in the igniter 211 . in response , the fluid flow in the proximity of a jet 214 achieves an elevated temperature and is ignited . a vent tube 232 allows the combustion and further passage of the fluid mixture from the detector 201 . the collector electrode 213 is electrically connected to an ion current measurement device ( not shown ) such as an electrometer which is used to measure the magnitude of ionization current that flows from the jet 214 to the collector electrode 213 . the resulting ion current is measured to provide a chromatogram . a fluid mixing structure 222 communicates with the fluid - directing structure 210 for directing the following fluids toward the igniter 211 : a first fluid supplied on a first fluid supply line 224 , a make - up fluid supplied on a make - up fluid line 225 , a first detector fluid supplied on a first detector fluid line 226 , and a second detector fluid supplied on a second detector fluid line 227 . preferably , the first fluid line 224 is integral with the column 14 and hence the first fluid comprises a heated , gaseous combination ( under pressure ) of the sample that is to be analyzed and a carrier gas . the make - up fluid also preferably comprises carrier gas ; the first detector fluid comprises pressurized hydrogen ( h 2 ) gas ; and the second detector fluid comprises air at ambient pressure and temperature . the make - up fluid and the first detector fluid are combined via a conduit 229 connected between the fluid mixing structure 222 , the make - up fluid line 225 , and the first detector fluid line 226 . also included are a make - up fluid pressure regulator 235 , a make - up fluid valve 225v , and a make - up fluid restrictor 225r ; first detector fluid valve 226v and restrictor 226r ; and second detector fluid valve 227v and restrictor 227r . in the instance that the detector 201 is constructed as a fid , it is contemplated that a predetermined pneumatic volume is provided in the second detector fluid line 227 between the valve 227v and the restrictor 227r . ( in the alternative instance that the detector 201 is constructed as a fpd , it is contemplated that a predetermined pneumatic volume would be provided in the first detector fluid line 226 between the valve 226v and the restrictor 226r .) the valves 225v , 226v , and 227v are preferably solenoid valves that are subject to the control of the pneumatic controller 26 as will be described in greater detail below . fig3 illustrates an alternative embodiment 202a of the pneumatic control section 201 of fig2 that is best suited for operation as an epc configuration . that is , in fig3 the valves 225v , 226v , and 227v are preferably provided in the form of proportional valves that are subject to the control of the pneumatic controller 26 according to signals received by the computer 22 from sensors 225s , 226s , and 227s , as will be described in greater detail below . preferably , such sensors are pressure sensors that provide sense signals indicative of the respective pressures in the make - up fluid line 225 , first detector fluid line 226 , and second detector fluid line 227 . in the embodiment illustrated in fig3 sensors 225s , 226s , 227s each sense a particular fluid parameter , such as fluid pressure or fluid flow , and transmits a feedback signal representative of such parameter to the computer 22 . by monitoring the sense signals from sensors 225s , 226s , 227s , the computer 22 can effect near - instantaneous alteration of the flow of each fluid that is provided to the detector 201 at any desired time . in the preferred embodiment of the computer 22 , the procedures necessary to set up or operate chromatograph 10 , so that a particular gas chromatographic separation test or analytical run can be conducted , are automated . the contemplated automation allows the operator to program events using programming via a table of fluid flow setpoints , a run table , and by clock time programming . a plurality of timed events may be programmed in each run table for execution during an analytical run . run time programming allows certain setpoints to change automatically during a run as a function of the chromatographic run time . for example , an event such as detector ignition may be programmed to occur prior to injection . such programming is contemplated as being applicable to the operation of the pneumatic controller , and particularly to the control of at least one of the first detector fluid flow and the second detector fluid flow . certain programmed steps effected by computer 22 in controlling the operation of the pneumatic controller 26 , which relate to and are in accordance with the present invention , are illustrated in fig4 and 5 . in the preferred embodiment , the operator may enter data regarding the operation of the pneumatic controller 26 into the computer 22 by use of the keypad 58 . the computer 22 operates to store the entered information into memory . the data thus entered may include one or more commands that are to be implemented immediately , or if necessary , the entered data may be stored in the form of one or more tables for later access . for example , the programmed events may be arranged in order of execution time in a run table . text denoting the characteristics of each event may be displayed on the display 60 . in the embodiments illustrated in fig2 and 3 , individual fluid streams combine to form a fluid mixture that is restricted to pass the igniter 211 and the collector electrode 213 . the flow characteristics and the composition of the fluid mixture that passes the igniter 211 will determine the success or failure of the ignition mechanism that occurs at the igniter 211 . hence , in a departure from the prior art , the content of the fluid mixture is temporarily altered during certain steps in an ignition sequence , so as to favor the ignition mechanism and thereby facilitate ignition . specifically , the flow of at least one of the fluid streams is modulated to effect either an increase or decrease in the fluid flow . accordingly , and in a particular feature of the present invention , a particular modulation of the flow of the first or second detector fluid during an ignition sequence has been found to facilitate detector ignition . such ignition has been successful in instances that may otherwise be unsuccessful due to the influence of the content and other characteristics of the fluid mixture . in the preferred embodiment , and as illustrated in fig4 and 5 , either the air flow rate or the hydrogen flow rate is modulated during a portion of the ignition sequence . the implementation of the modulation will differ slightly according to whether the embodiments of fig2 or fig3 are provided . because the flow through the solenoid valves shown in the configuration in fig2 can only be turned on or off , rather than varied continuously , a modulated flow is preferably achieved by cycling the appropriate valve ( valve 227v or fid , valve 226v for fpd ) on and off , starting at a low duty cycle and increasing it ( preferably at a fixed frequency ) until full flow is attained . in the configuration illustrated in fig3 the contemplated epc achieves a modulated flow by opening the appropriate valve ( valve 227v for fid , valve 226v or fpd ) in a continuous ramp , starting at a low value and increasing it until full flow is attained . in an instance of non - epc control , the second detector fluid flow is best modulated by a solenoid valve according to the practice of : a ) fixing the flow duty cycle and varying the frequency of modulation ; b ) fixing the frequency of modulation and varying the flow duty cycle ; or c ) varying both the flow duty cycle and the frequency of modulation . preferably , a fixed frequency option is selected because it is the easiest to implement in firmware resident in the computer 22 . the preferred frequency of modulation is chosen to offer : d ) for all operating conditions , a predetermined range of duty cycles that will result in ignition , and e ) for the most severe conditions ( such as may be found during a very high second detector fluid flow and when helium is used as the make - up gas ), the greatest span of duty cycles which will result in ignition . in another feature of the present invention , the aforementioned criteria may be applied to a particular chromatograph 10 such that a modulation envelope may be predetermined to provide the requisite flow modulation that will facilitate , if not ensure , a successful ignition even under worst case conditions . in a further aspect of the present invention , in the ignition of a fid , the make - up fluid flow is discontinued during a portion of the ignition sequence and then resumed after the flame is lit . in a still further aspect of the present invention , in the ignition of a fid , the first fluid flow is discontinued during a portion of the ignition sequence and then resumed after the flame is lit . in the preferred embodiment of the chromatograph 10 , detector 24 is provided as a plurality of separately located detectors , e . g ., a front detector and a back detector . also in the preferred embodiment , the first detector fluid is provided as hydrogen gas . fig4 illustrates a first preferred ignition sequence that is pertinent to the operation of the chromatograph 10 when one such detector 24 is provided in the form of an fid . in the preferred embodiment , each of the first , second , and third delay periods are approximately 2 - 3 seconds . fig5 illustrates a second preferred ignition sequence that is pertinent to the operation of the chromatograph 10 when one such detector 24 is provided in the form of an fpd . in the preferred embodiment , each of the first , second , and third delay periods are approximately 1 - 2 seconds . the advantages of the above - described embodiments were demonstrated in a series of ignition repeatability experiments performed on a test apparatus that included a fid mounted in a hewlett - packard hp5890 gas chromatograph . pneumatic control was provided according to the non - epc configuration illustrated in fig2 . consistent ignition was found to occur according to certain criteria , as will now be described . one modulation frequency that was found to satisfy these criteria in the chromatograph under test was 0 . 5 cycles / sec . a slow duty cycle was found to be preferable because the time demands on the firmware in the computer 22 are lessened and any differences in valve actuation speed are less likely to affect the success of the ignition . based on the test data , the preferred duty cycle started at 10 % and was stepped through several duty cycles until at least 60 %, at which point the relevant valve can remain full - on . adding a pneumatic volume between the valve 227v and the frit 227f was found to reduce the necessary frequency of actuation and , in addition , increase the range of duty cycling at which the flame will ignite . a volume of 1500 mm 3 was found to be the preferred amount . fig6 - 9 illustrate the test results that indicate the effect of certain operating conditions in the chromatograph upon ignition , according to a relationship between flow duty cycle and modulation frequency . in each instance , a successful ignition was found to occur within one or more particular modulation envelopes , each of which relate a range of flow duty cycles and modulation frequencies . the illustrated modulation envelopes are provided as examples of modulation envelopes that were particularly successful is achieving consistent ignition in the fid of the test apparatus , and in no way should be considered limiting . fig6 shows first ( a ), second ( b ), and third ( c ) modulation envelopes realized in the aforementioned test apparatus according to a variation in pneumatic volume . the response curves ( a ), ( b ), and ( c ) correspond to the pneumatic volume being implemented as 1500 mm 3 , 3000 mm 3 , and 785 mm 3 respectively . fig7 shows a modulation envelope realized in the aforementioned test apparatus according to an interruption in make - up gas during the ignition sequence . fig8 shows first ( a ) and second ( b ) modulation envelopes realized in the aforementioned test apparatus according to differing air flow rates during the ignition sequence . the first and second response curves ( a ) and ( b ) correspond to the air flow rates being implemented as 400 milliliters / minute and 650 milliliters / minute , respectively . fig9 shows first ( a ) and second ( b ) modulation envelopes realized in the aforementioned test apparatus according to differing jet orifice sizes that were used during the ignition sequence . the first and second response curves ( a ) and ( b ) correspond to the jet orifice being implemented as 0 . 030 inches and 0 . 011 inches , respectively . fig9 illustrates at least two worst case ignition conditions . by satisfying the ignition flow requirements via valve modulation rather than diverting fluid flow , the preferred embodiment may be constructed without a diverter valve and the associated costs of tubing and fittings , additional assembly labor , and machining of parts . reliability and ease of use are increased . the presence of make - up gas and / or carrier gas , each of which undermines successful ignition by diluting the hydrogen and oxygen in the fluid mixture and by cooling the igniter , may be eliminated during a portion of the ignition sequence . in contrast to systems constructed according to the prior art , a successful ignition in the preferred embodiment is not as subject to manufacturing production variations . heretofore , a normal variation in , for example , the gas source pressure , which may stray out of the range required by an operating condition for proper ignition would cause the operator to experiment with differing source pressures to try to find a reliable operating region . in the preferred embodiment , the first or second detector fluid flow is modulated during the ignition sequence and therefore will pass through the optimum fluid mixture that facilitates ignition . the modulation is automatically effected during the ignition sequence , in a manner not generally noticeable by the operator , thereby ensuring a reliable flame ignition . although the invention has been described with reference to the above - described preferred embodiments , variations and modifications are contemplated as being within the scope and spirit of the present invention .	6
the present invention is hereinafter further described with reference to accompanying drawings by using embodiments . a method for identifying and extracting ideographic components is oriented to a bilingual sentence pair of same semantic content , where a sentence alignment operation is performed by using a software method and man - human interactions , and texts of languages a and b of same semantic content are stored in word fields of language a and word fields of language b in a sentence database ( this part is similar to translation memory in the prior art ). the present invention requires that samples of extracted ideographic components should be standard , for example , extracted from issued essays or works such as textbooks , model essays , and special reference documents . an operating principle is that a user who identifies and extracts ideographic components and a person who collates sentence pairs for semantic content alignment cannot modify content of an operated sentence pair . with reference to fig1 , which is a flowchart of extracting ideographic components , by using chinese and english languages as an example , the following further describes the method for extracting ideographic components . as shown in fig1 , this method includes the following four steps : herein concepts that have special meanings are defined and abstracted as follows : sentence : in a language text , a basic unit that expresses complete semantic content is a sentence . sentences in different language texts may express same semantic content . a sentence may include two parts : a sentence frame and a sentence cabin , where one sentence frame includes at least one sentence cabin . sentence frame : a residual part after sentence cabins are removed is a sentence frame . the sentence frame is the frame of a sentence . it is originated from abstraction of a type of sentence , is relatively stable in the sentence , and reflects the basic semantic content and type of the sentence . it constitutes the basic frame part of this type of sentence . the sentence frame reflects basic semantic content and type of the sentence and is oriented to the whole mankind and are language - independent , while the basic frame is oriented to a specific natural language . sentence cabin : the parts that are embedded in the sentence frame , namely , the basic frame , and are often replaced flexibly , are sentence cabins . the sentence frame plays a role in selecting and constraining sentence cabins . the sentence cabins may be filled or replaced with sense group strings and form specific diversified sentences . the quantity and semantic content of sentence cabins are oriented to the whole mankind and are language - independent , but positions and sequences of the sentence cabins in the sentence frame and sense group strings for filling therein are oriented to specific natural languages . idiom : an idiom is a sentence that cannot be divided into a sentence frame and a sentence cabin because it is too short , or is a sentence that cannot be divided into a sentence frame and a sentence cabin because of languages or customs . the idiom is a type of special sentence . for example , sentences that cannot be divided into sentence frames and sentence cabins because of languages or customs include : “ , , ”; “ one boy is a boy , two boys half a boy , three boys no boy .”; “ ” there can never be too much deception in war .” no word string has a same sense , and it is difficult to extract or label the sentence cabins . in chinese , some idioms , common sayings , proverbs , two - part allegorical sayings , and so on , are also idioms . the sentence frame and sentence cabin are like a blank filling question , where the sentence frame is a question stem and the sentence cabin is a blank . they are like a mathematical formula , where the sentence cabin is a variable and the sentence frame is an equation . the sentence cabin is filled with or composed of sense group strings led by sense groups . however , sizes of sentence cabins vary greatly . a smallest sentence cabin includes only one sense group string , while a largest sentence cabin may include a subordinate clause or a clause . sentence cabins are classed into two types : simple sentence cabin and complex sentence cabin . after a sentence pair is read into a bilingual sentence database ( 101 ), the sentence pair needs to be matched with a sentence frame . if there is a sentence frame , and after the sentence pair is integrated into the sentence frame , each sentence cabin and cabin eye are even and complete without stacking , the sentence pair is skipped . a sentence frame needs to be extracted only when the sentence pair does not match any sentence frame . first an operation of matching a sentence frame is performed . in matching a sentence frame , a sentence frame word string table is generated in advance according to a cavity between a sentence frame word string and a sentence cabin , and is indexed , for example , a sentence frame is “ i know +[ 1 ]+ got crush on +[ 2 ]+, +[ 3 ]+ you could +[ 4 ]+ . . . ”, “ +[ 1 ]+ +[ 2 ]+ , +[ 3 ]+ +[ 4 ]+ ”, so that it becomes a sentence frame word string “ i know . . . got crush on . . . , . . . you could . . . . ”, “ . . . . . . . . . . . . ”; they are jointly tabulated and indexed with a sentence frame code and a frame header . the sentence frame word string is divided by sentence cabins into sentence frame word segments , for example , “ i know ”, “ got crush on ”, “,”, “ you could ”, “.”; “ ”, “ ”, “ ,”, “,”, “ ”, “ ”. it is noted that “,” and “.”, like “ got crush on ”, are also a sentence frame word segment . sentence frame match operation : the machine generates and indexes a sentence frame word string table in advance according to a cavity between a sentence frame word string and a sentence cabin . when matching a sentence frame , the machine fetches english words and chinese characters one by one from a sentence example from left to right , searches for a frame header field ( in english , the first word or symbol of a sentence frame word string is included ; in chinese , the first word or punctuation is included ) in the sentence frame word string table , and saves a search result to a temporary table . then the machine fetches content of the temporary table from the records in succession , and inquires sentence pair examples by using sentence frame word segments . if each segment of the sentence frame word string may be found in the sentence pair examples and sequences thereof in sentence frames are the same , those sentence frames are matched sentence frames . then the machine fetches the sentence frame of the corresponding language according to a sentence frame code field of the sentence frame word string table . in the sentence frame match operation , a matched sentence frame is searched out , the current sentence pair example is integrated into the sentence frame , and “ cabin detection ” and “ search , match , and label ” buttons are displayed and provided . when a user considers , after reading , that each sentence cabin and cabin eye are even and complete without stacking ( this is an unexpected gain , because the user knows by a glimpse whether semantic content is appropriate ), and that the semantic content is correct , the user clicks the “ cabin detection ” button to indicate approval . the machine continues a cabin detection step . otherwise , the provided result is not approved , and the “ search , match , and label ” button is clicked . the machine performs a “ search , match , and label ” operation , and inquires , by using word strings of language a , a conventional electronic dictionary to see whether word strings of language b corresponding to the word strings of language a are included in the sentence of language b , and generates a semantic match table for the current sentence pair . “ search , match , and label ” operation : in a “ search , match , and label ” operation , the machine uses a match table including part - of - speech fields , word fields of language a , and word fields of language b , first performs segmentation in units of word strings of the sentence of language a and fills in the word fields of language a in the match table sequentially , then fetches the word strings from the records one by one and inquires the conventional electronic dictionary , and uses the obtained corresponding explanations of language b to search to determine whether the sentence of language b includes the explanations . if an explanation is included and is the longest string , the machine fills in the word field of language b with the string and fills in the part - of - speech field with the part of speech thereof . if no explanation is included , the word field of language b is empty . now a preparation is made for identifying and labeling sentence cabins . n is set to 0 , and a counter of sentence cabins is cleared . hereinafter concepts that have special meanings are defined and abstracted as follows : simple sentence cabin : if the count of word strings in a pinyin text in a sentence cabin is not greater than five original word strings or a sentence cabin includes not more than three sense group strings except non - ideographic function words , the sentence cabin is called a simple sentence cabin . repetitive sentence cabins : sentence cabins with completely same sentence cabin content and a same number are repetitive sentence cabins . in a sentence pair , the quantity and positions of repetitive sentence cabins in two sentences are not necessarily equal . continuous sentence cabins : two sentence cabins connected without a separating word string ( or character ) in between are continuous sentence cabins . the quantity of continuous sentence cabins in a sentence pair is strictly limited , and only two continuous sentence cabins are allowed . if three continuous sentence cabins appear in either of two sentences , the work and operation must be redone . complex sentence cabin : a sentence cabin that is greater than a simple sentence cabin is a complex sentence cabin . a sentence cabin including a cabin model is a sentence cabin with a model and is generally greater than or equal to eight original word strings . a group string sentence cabin generally includes a complex word string , and is greater than a simple sentence cabin but smaller than a sentence cabin with a model . cabin model and cabin eye : by further analyzing the complex sentence cabin , it is derived that a part like a frame part is called a cabin model and that a replaceable part embedded in the frame of the cabin model is called a cabin eye . the sentence cabin and cabin eye are a superordinate concept and a subordinate concept , but the size of the simple sentence cabin is equal to that of the cabin eye . automatic identification is oriented to the foregoing match table , and features of content of automatic identification are as follows : quantity string : all chinese and english word strings indicating “ number ” and “ quantity ” are collected and recorded in a quantity table . in the table , there are fields such as english quantity , chinese quantity , calculation value , and part of speech , where the part of speech includes “ calculation string ”, “ digital string ”, “ cardinal number ”, “ ordinal number ”, “ quantity ”, and so on . if calculation is required , a quantity string is segmented in words from left to right ; the table is inquired , and if the part of speech thereof is labeled with “ calculation string ”, it is added as a calculation value to result number a ; if it is a digital string , the digital string is multiplied by result number a and then is added to result number b after completion of the operation . in judging whether a string is a quantity string , a string recorded in the table is identified as a quantity string . if the quantity string in the match table is followed by a noun that is recorded and identified in the quantity table as a quantifier , the two are combined into a quantity string . proper noun string : by using english capital initials , all words beginning with a capital letter except in other capitalization cases are identified as proper noun strings . article noun string : an english article is used for identification . a noun following an article , or an “ article adjective noun ” inserted with an adjective is identified as an article noun string . zero - article noun string : a string that does not begin with an article but whose part - of - speech field is a noun and whose word field of language a and explanation field of language b are not empty , is identified as a zero - article noun string with equivalent semantic content . other match strings : other types of words , as long as their word fields of language a and explanation fields of language b are not empty , are identified as other match strings with equivalent semantic content . continuation : the machine identifies the bilingual quantity string , proper noun string , and article noun string sequentially simultaneously , and pre - labels them as sentence cabins according to a time sequence by using n = n + 1 . operation of automatically identifying the pre - labeled sentence cabins : for example , a sentence pair example is : “ in hengtung county , its per - mu_grain_yield surpassed 800 jin in 1970 , double that before 1965 . the machine inquires a semantic match table of the current sentence pair , first searches for and identifies quantity strings , and if quantity strings exist , simultaneously pre - labels the quantity strings with “ a , b , c . . . ” according to n = n + 1 . in this example , three pairs of quantity strings exist and are pre - labeled as three sentence cabins “ a , b , and c ”, for example , “ in hengtung county , its per - mu_grain_yield surpassed a { 800 jin } in b { 1970 }, double that before c { 1965 }. if no quantity string exists or after the machine identifies and searches for quantity strings in the whole sentence completely , the machine identifies and searches for proper noun strings . if proper noun strings exist , the machine also pre - labels them with “ a , b , c . . . ” according to n = n + 1 . in this example , one pair of proper noun strings exists and continues to be pre - labeled as a sentence cabin “ d ”, for example , “ in d { hengtung county }, its per - mu_grain_yield surpassed a { 800 jin } in b { 1970 }, double that before c { 1965 }. if no proper noun string exists or after the machine identifies and searches for proper noun strings in the whole sentence completely , the machine identifies and searches for article noun strings . if article noun strings exist , the machine also pre - labels them with “ a , b , c . . . ” according to n = n + 1 . no article noun string exists in this example . if no article noun string exists or after the machine identifies and searches for article noun strings in the whole sentence completely , the machine displays a symbol “\|” and displays “←” and “→” command buttons on two sides respectively , calculates and displays a frame example percentage , and a “√” command button , and accepts the user &# 39 ; s correction or approval ; meanwhile displays the frame example percentage as “ 64 %”. the percentage does not reach a criterion 15 - 50 %. therefore , the machine needs to continue to identify and label sentence cabins , accepts the user &# 39 ; s click on the “√” button , and continues identification and labeling . quantity strings , proper noun strings , and article noun strings of two languages are simultaneously identified sequentially above . after the three types of word strings are identified , the machine calculates the frame example percentage , and displays and provides a pre - labeling result and some command buttons simultaneously . if a correction is required , the machine may accept a user &# 39 ; s ( namely , the user , same hereinafter ) correction . if no correction is required but the frame example percentage exceeds the criterion , as in this example , the machine continues identification and labeling . if the frame example percentage is higher than 15 - 50 %, the machine searches according to the match table , where those whose part - of - speech fields are nouns and whose word fields of language a and word fields of language b are not empty are semantic match zero - article noun strings , or those whose part - of - speech fields are not nouns but whose word fields of language a and word fields of language b are not empty are other semantic match word strings . meanwhile , the machine displays the semantic match table of the current sentence pair , “ hand ”, “ v ”, “& lt ;∩”, and “ format check ” buttons . in this example , the machine continues to identify zero - article noun strings and other semantic match word strings . it is noted that from now , the machine pauses every time when one sentence cabin is identified and pre - labeled and waits for interactive approval or correction . for example , the machine searches for zero - article noun strings from left to right and there are “ per - mu_grain_yield ” and “ ”, which are both separated from previous and next labeled sentence cabins by word strings , and therefore further pre - labels a sentence cabin “ e ”, for example , “ in d { hengtung county }, its e { per - mu_grain_yield } surpassed a { 800 jin } in b { 1970 }, double that before c { 1965 }. in this case , the frame example percentage “ 42 %” already reaches the criterion , but is not smaller than or equal to 15 %. therefore , the user may end identification according to the semantic case , and click the “ format check ” button ; or may perform identification and pre - labeling , and click the “√” button ; or may use other command buttons to make corrections . the correcting operation is associated with the foregoing displayed command buttons , which are enumerated as follows : “ ” buttons : when a sentence to be corrected is clicked , insert and display “\|” at the clicked point , and then judge whether “←” and “→” buttons are clicked ; when “←” is clicked , move the left word string of “\|” to the left : if “\|” is in a sentence cabin , move the left word string of “\|” out of the sentence cabin ; if “\|” is out of the sentence cabin , move the left word string of “\|” into the sentence cabin . when “\|” is clicked , move the right word string of “\|” to the right ; if “\|” is in the sentence cabin , move the right word string of “\|” out of the sentence cabin ; if “\|” is out of the sentence cabin , move the right word string of “\|” into the sentence cabin . thereby , content of the sentence cabin is increased or decreased . “√” button : approve the currently identified and pre - labeled sentence cabin , and continue to identify and pre - label a new sentence cabin . “\| hand \|” button : manually identify a sentence cabin , meanwhile respectively click the header and tail of each sentence cabin to be pre - labeled , in the sentences to be corrected of languages a and b , then click the “\| hand \|” button , pre - label them as a pair of sentence cabins , and automatically modify the frame example percentage . “& lt ;∩” button : click each time to draw back the last identified and pre - labeled sentence cabin , and restore to the state and frame example percentage before the last pre - labeling . this operation may be repeated until all sentence cabins are removed . “ format check ” button : end the correcting operation on the current sentence pair , and perform a format check operation . the format check includes three steps : redo check , label format check , and formal labeling . the specific operation is as follows : the length of a sentence frame is limited to be smaller than or equal to 200 characters for english sentences , and limited to be smaller than or equal to 150 characters ( one chinese character is counted as two bytes ) for chinese sentences ; the quantity of continuous sentence cabins is limited to two connected sentence cabins . once it is found that the sentence frame length exceeds the limit or that three sentence cabins are connected , a report is generated immediately , and work should be redone immediately . the automatic identification and pre - labeling of sentence cabins described above are performed according to the following “ rule for labeling sentence frames and sentence cabins ”. herein the label format check is also a check performed according to this rule . if there are incompliant parts , the incompliant parts are modified automatically if they can be modified automatically ; or the user is prompted to make modifications if they cannot be modified automatically . after completion of the check , a search is performed to determine whether continuous sentence cabins having same numbers simultaneously exist in sentences of languages a and b , and if so , a dialog box is displayed to obtain the user &# 39 ; s approval and then the continuous cabins are merged into one sentence cabin . the continuous sentence cabins having same numbers simultaneously , for example , connected sentence cabins “ c , d ” or “ d , c ” included in both sentences of languages a and b , should be merged after an interaction ( decided by the user certainly ). then the next step is performed . chinese and english are the first language pair extracted in the identification and comparison . according to the english sentence , numbers are arranged in an ascending order from left to right . the sentence cabins are formally labeled with numbers “ 1 , 2 , 3 . . . ”. starting from a third language , the labeled sentences are used as samples for replication , identification , and labeling , and no pre - labeling is required . { circle around ( 1 )} a sentence frame includes three types of components : sentence frame word , sentence cabin , and punctuation . “+” must be used for separation between a sentence cabin and the other two types of components , and between sentence cabins . punctuations are labeled in the same ways as sentence frame words . for example , { circle around ( 2 )} a punctuation is equivalent to a sentence frame word . the punctuation at the end or in the middle of the sentence is separated by a space in english , but not separated in chinese . for example , { circle around ( 3 )} the first word of the sentence frame in english is not capitalized ( except “\|”), including an irregular word , inflectional ending , and so on ( should be consistent with the example ). for example , { circle around ( 4 )} all short forms are converted into full spellings regardless of whether they are in the sentence frame or sentence example . { circle around ( 5 )} chinese and english are the first language pair . according to the english sentence , sentence cabin numbers are arranged from left to right in an ascending order . those of chinese and other languages all correspond to the sentence cabin numbers of the english sentence according to the semantic content . there are two forms : a sentence frame form and a frame example form . the former uses square brackets , and the latter uses braces . ( a ) in the sentence frame form , such as a sentence frame 263 : ( b ) in the frame example form , the only difference lies in positions of numbers of sentence cabins . for example , the frame example form of the sentence frame 263 is : 1 { at_that_time they } could not afford 2 { the ordinary comforts of life }, not to speak of 3 { luxuries }. { circle around ( 6 )} repetitive sentence cabins have a same sentence cabin number and same sentence cabin content . they do not necessarily correspond each other between languages . their labels are also the same . for example , { circle around ( 7 )} the label of a cabin model is consistent with that of a sentence frame , and also has two corresponding forms . the cabin model number is placed in parentheses “( )” and located at the beginning of the sentence cabin , for example , the 1 { fisherman } consents to return 2 { the feather suit }, on condition that 3 {( 00205 ) 1 [ fairy ] 2 [ dance ] and 3 [ play heavenly music ] for him }. 3 {( 00205 ) 1 [ ] 2 [ ] 3 [ ]} , 1 { } 2 { }. { circle around ( 8 )} the foregoing parentheses , square brackets , and braces used for labeling all occupy a single byte for chinese , english , and other languages . continuation : for the current sentence pair example , identification and labeling of sentence cabins are all completed . for example , “ in 1 { hengtung county }, its 2 { per - mu_grain_yield } surpassed 3 { 800 jin } in 4 { 1970 }, double that before 5 { 1965 }. some content about identification and pre - labeling of sentence cabins of the current sentence pair example is still not involved . therefore , another example is provided for description . for example , a sentence pair is read : “ for three years , there is been a running fight between the tory and labour members of the housing committee about raising council ho house rents .”, “ 3 , ” as described above , a quantity string , a proper noun string , and an article noun string are automatically simultaneously identified sequentially . a prompt is displayed , saying “ the article noun string “ running ” does not match !” after the three types of word strings are identified and sentence cabins are pre - labeled , the frame example percentage is displayed as 59 %. the pre - labeling result is : “ for a { three years }, there is been a running fight between b { the tory } and c { labour members } of d { the housing committee } about raising council house rents .”: the content that is not involved in the previous example appears in this example . the processing is the same as above , and the machine additionally displays the semantic match table of the current sentence pair , “\| hand \|”, “ v ”, and “∩” buttons , and accepts the user &# 39 ; s modification of the match table or addition of semantic match word strings by using a sense group alignment method such as composing complex words , extending senses of words , or adding characters or words ahead or behind , and continues to pre - label sentence cabins . in the identification and pre - labeling of the quantity string , proper noun string , and article noun string , a prompt “ the article noun string “ running ” does not match !” is displayed . in the match table , a field of language b corresponding to “ running ” in language a is empty and therefore is not matched ; explanations about “ running ” in the conventional electronic dictionary include : “ n , ; ; ; ; adj , ; ; ; ; ;”. none of them is included in the sentence of language b during the search and therefore is not matched . according to semantic content of the current sentence pair example , the running expresses a sense of “ ”, which is an extension of the senses of “ ” and “ ”. it complies with the operation requirement of “ sense group alignment ” ( described in detail later ). therefore , “ ” is added to the field of language b ( the part - of - speech field is filled with “ t ”, indicating other supplementary word types , the same hereinafter ), so that “ running ” and “ ” are matched to form a sense group string . however , the article noun string “ a running fight ” and “ ” are matched , and are identified and pre - labeled as a sentence cabin “ e ”; the frame example percentage is 48 %. for example , “ for a { three years }, there is been e { a running fight } between b { the tory } and c { labour members } of d { the housing committee } about raising council house rents .”; 48 % no sentence cabin exists in the last part of the sentence pair , and the frame example percentage is 48 %. the machine may continue to pre - label sentence cabins . in the match table , “ council ” cannot be matched in the last “ raising council house rents ” and “ ”. in the conventional dictionary , senses of “ council ” include “ n , ; ; ; ; ; ; ; ; ”, and herein it expresses a sense of “ ”, and is an extension of the sense of the original word string . it complies with the operation requirement of “ sense group alignment ”. therefore , the explanation “ ” is added to the field of language b . when the user clicks the “√” button , automatic identification and pre - labeling are continued as follows : for a { three years }, there is been e { a running fight } between b { the tory } and c { labour members } of d { the housing committee } about f { raising council house rents }. a { 3 } , d { } b { } c { } f { } e { }. in this case , the frame example percentage is 26 %; and distribution of the sentence cabins is rational ( an interval between cabins is generally 1 - 5 strings ). the operation of identification and pre - labeling ends ; the click on the “ format check ” button is accepted . a format check operation is performed . then formal labeling is : for 1 { three years }, there is been 2 { a running fight } between 3 { the tory } and 4 { labour members } of 5 { the housing committee } about 6 { raising council house rents }. two sentence pair examples are provided above , and are both paused after formal labeling . continued from the foregoing sentence pair example 1 , after formal labeling , the sentence pair example is : 1 { in hengtung county }, 2 { its per - mu_grain_yield } surpassed 3 { 800 jin } in 4 { 1970 }, double that before 5 { 1965 }. in this case , the quantity of sentence cabins is 5 , which satisfies the “ n =& gt ; 1 ” requirement ; then the residual parts after content of the sentence cabins is removed are sentence frame components , for example , the sentence frame components are stored in corresponding language component fields of a sentence frame database respectively . herein , for example , the english sentence frame “ in +[ 1 ]+, its +[ 2 ]+ surpassed +[ 3 ]+ in +[ 4 ]+, double that before +[ 5 ]+.” is stored in the “ english sentence frame ” field of the sentence frame database ; and the chinese sentence frame “[ 1 ]+ +[ 4 ]+[ 2 ]+ +[ 3 ]+, +[ 5 ]+ ” is stored in the “ chinese sentence frame ” field of the sentence frame database . hereinafter , xxxx components are stored in corresponding language component fields in an xxxx database , and so on . there are sentence frame fields of multiple languages such as “ english sentence frame ”, “ chinese sentence frame ”, and “ russian sentence frame ” in a sentence frame database ( 105 ), which are respectively used to store sentence frames of corresponding languages . semantic content of sentence frames of multiple languages in a same record is the same . in the second round of semantic comparison and sentence frame extraction , the labeled language sentences are used as a template to identify and label the sentence cabins . after the sentence frame of the new language is obtained , the sentence frame database is searched by using the labeled language sentence frame , and the sentence frame is stored in the corresponding field of the new language in the same record . continued from the foregoing sentence pair example 2 , after formal labeling , the sentence pair example is : for 1 { three } years , there is been 2 { a running fight } between 3 { the tory } and 4 { labour } members of 5 { the housing committee } about 6 { raising council house rents }. in this case , the quantity of sentence cabins is 6 , which satisfies the “ n =& gt ; 1 ” requirement ; then the residual parts after content of the sentence cabins is removed are sentence frame components , for example , like the foregoing example , they are respectively stored in the “ english sentence frame ” and “ chinese sentence frame ” fields in the same record of the sentence frame database . many things grow in the garden that were never sown there . no sentence frame is matched in the operation of matching a sentence frame . then a “ search , match , and label ” operation is performed . there are 12 records in the match table after the “ search , match , and label ” operation . fields of language a are words and full stops of the english sentence . fields of language b are all empty . in the “ search , match , and label ” operation , no string is matched . then the operation of identifying and labeling sentence cabins is performed , but there is no sentence cabin that can be labeled . this satisfies n = 0 . they are idiom components . they are respectively stored in the “ english idiom ” and “ chinese idiom ” fields in a same record of an idiom database . there are idiom fields of multiple languages such as “ english idiom ”, “ chinese idiom ”, and “ russian idiom ” in an idiom database ( 104 ), which are respectively used to store the idioms of the corresponding languages . semantic content of idioms of multiple languages in a same record is the same . in the second round of semantic comparison and idiom extraction , the labeled language sentences are used as a template to identify and label the idioms . after the idiom of the new language is obtained , the idiom database is searched by using the labeled language idiom , and the idiom is stored in the corresponding field of the new language in the same record . the step of identifying and labeling the sentence cabins is completed . the obtained sentence frame components and idiom components are respectively stored in the sentence frame database and idiom database . ( iii ) detecting cabins and extracting a cabin model ( 106 ) sentence cabins are detected one by one sequentially . in the first round of comparison , word strings included in english sentence cabins are counted . if the quantity of word strings included in a sentence cabin is smaller than eight original word strings , complex words are composed according to requirements . if complex words do not need to be composed , this operation is skipped . if the quantity of word strings included in a sentence cabin is greater than or equal to eight original word strings , a “ search , match , and label ” operation is performed by using the current sentence cabin , and a semantic match table is generated for the current sentence cabin , so that a cabin model is further extracted as a sentence cabin with a model , for example , 1 { the american } 2 { economic } machine is , organized around 3 { a basically private - enterprise }, 4 { market - oriented economy } in which 5 { consumers } largely determine 6 { what shall be produced } by 7 { spending their money in the marketplace for those goods and services that they want most }. 1 { } 2 { } 3 { } 4 { } , 2 { } , 5 { } 7 { } 6 { }. 6 { }. the sentence cabins are detected one by one sequentially . none of the sentence cabins numbered 1 - 6 exceeds eight original strings . a sentence cabin 7 { spending their money in the marketplace for those goods and services that they want most } exceeds eight original word strings . a “ search , match , and label ” operation is performed and a semantic match table is generated for the current sentence cabin , so that a cabin model is further extracted as a sentence cabin with a model . the cabin model is extracted , and bilingual quantity strings , proper noun strings , and article noun strings are simultaneously identified sequentially and pre - labeled as cabin eyes . for example , the current cabin is labeled as : spending their money in a [ the marketplace ] for those goods and services that they want most in this case , the model example percentage is 81 %, greater than 50 - 70 %. then zero - article noun strings or other semantic match word strings are labeled as cabin eyes one by one under a prerequisite that spacing exists . the user can not only perform approval or correction , but also modify the match table by using a sense group alignment method such as composing complex words , extending senses of words , or adding characters or words ahead or behind , add a semantic match word string , and continue to pre - label cabin eye b . spending their money in a [ the marketplace ] for those b [ goods and services ] that they want most in this case , the model example percentage is 65 %, which is between 50 % and 70 %. the labeling operation may be ended or sentence cabin c may be further pre - labeled according to requirements of semantic content . spending their money in a [ the marketplace ] for those b [ goods and services ] that c [ they want most ] in this case , the model example percentage is 53 %, which is lower than 50 - 70 %. labeling cannot be performed any more . the previous labeling is drawn back and restored . eye labeling ends . the pre - labeled cabin eyes are modified into formally labeled cabin eyes for the english sentence cabins from left to right . for example , the current sentence cabin is formally labeled as : spending their money in 1 [ the marketplace ] for those 2 [ goods and services ] that 3 [ they want most ] the extracted cabin model of the current sentence cabin includes two cabin eyes , which satisfies the condition of the cabin model n =& gt ; 1 . residual parts after cabin eye content is removed are cabin model components . for example , the cabin models obtained in current extraction are saved to corresponding language component fields in a cabin model database ( 107 ). there are cabin model fields of multiple languages such as “ english cabin model ”, “ chinese cabin model ”, and “ russian cabin model ” in the cabin model database ( 107 ), which are respectively used to store the cabin models of corresponding languages . semantic content of cabin models of multiple languages in a same record is the same . in the second round of semantic comparison and cabin model extraction , the labeled language sentences are used as a template to identify and label the cabin models . after the cabin model of the new language is obtained , the cabin model database is searched by using the labeled language cabin model , and the cabin model is stored in the corresponding field of the new language in the same record . then the machine continues to detect other sentence cabins , until detection of sentence cabins of the whole sentence pair is completed . the current cabin model is the last sentence cabin of the current sentence pair example . therefore , detection of sentence cabins of the whole sentence pair is completed . the current sentence cabin is integrated back into the current cabin model . the frame example form of the whole sentence pair is as follows : 1 { the american } 2 { economic } machine is , organized around 3 { a basically private - enterprise }, 4 { market - oriented economy } in which 5 ( consumers ) largely determine 6 { what shall be produced } by 7 {( 2301 ) spending their money in 1 [ the marketplace ] for those 2 [ goods and services ] that 3 [ they want most ]}. 1 { } 2 { } 3 { } 4 { } , 2 { } , 5 { } 7 {( 2301 ) 1 [ ] 3 [ ] 2 [ ] } 6 { }. herein concepts that have special meanings are defined and abstracted as follows : sense group : a sense group is equivalence and unification of a “ sense ” of a character , a word , a word combination , or a phrase of a natural language and is a basic unit of human thinking activities . the sense group is not limited to languages but belongs to the whole mankind , and is also metabolized with development of the human society . sense group string : a corresponding expression of the sense group in a language text is called a sense group text string , sense group string for short . a sense group string in a pinyin text is classified into a single string and a complex string . a string including only one original word string is a single string . a string composed of two or more than two original word strings and connected with “ _ ” is a complex string . sense group alignment : the sense group alignment method uses the language - independent feature of the sense group to perform semantic alignment on the characters , words , word combinations , or phrases of multiple languages under the support of the current sentence pair example . after alignment , they become a sense group string and are eligible for being stored in a sense group database . mainly the following methods are available : { circle around ( 1 )} composing complex words : judgment is performed according to the semantic content of the current sentence pair and sentence cabin . if one of them requires that two or more original word entries should be merged , so that the semantic content is the same as that of another word entry , the original word entries are connected by using “-” and merged into one word entry , which is called a complex word . alternatively , when total semantic content of two or more original word strings cannot be obtained by addition of the semantic content of the word strings , the word strings are connected by using “ _ ” to form a complex word ( complex string ): with respect to “ works little ” “ ”, although a sense of “ works ” is “ ”, “ little ” does not have a sense of “ ”; the total semantic content of the two words cannot be obtained by addition of the word strings ; therefore , they are connected by using “ _ ” to compose a complex word . { circle around ( 2 )} according to the current sentence pair example , extending or supplementing semantic content of a word . the senses of “ useful ” include “ , ,”, and definitely the semantic content “ ” is expressed in the sentence pair ; in addition , senses of “ ” and “ ” are similar . therefore , the sense entry “ ” is added or extended . the sense entry “ ” is added for “ small ” according to the sentence pair example . { circle around ( 3 )} increasing or decreasing a string length under a prerequisite that the original characters and words are not changed , for ease of splicing . “ teach ” v has senses of “ , ”; the length of the word string is reduced to “ ”, and the sense entry “ ” is added . for example , words are added to change “ good ” into “ ”. for example , a word is added to change “ word ” into “ ”. { circle around ( 5 )} inflectional forms of words are recorded in the database as new word entries ( for semantic content expressed by participles and comparative degrees , new word entries and corresponding senses of the words ). for “ been ”, senses of “ ” are added . for “ punished ”, a sense of “ ” is added . the sense group alignment method is as important as the sentence frame match operation and “ search , match , and label ” operation , and is also indispensable to the method of the technology . the sense group database overlaps the conventional dictionary and electronic dictionary , and the original vocabulary is basically incorporated . a difference is related to sense group alignment . inflectional forms of words are recorded as new word entries . sense group alignment increases the relative quantity of word entries and makes great contributions to splicing . complex words and terms can all be covered . continuation : referring to the foregoing semantic match table after the identification and labeling of sentence cabins , bilingual word strings with aligned semantic content in the sentence cabins or cabin eyes are determined to be sense group strings , and are stored in pairs one by one in the corresponding language component fields in the sense group database ( 109 ). the operation of comparison and extraction of the current sentence pair ends , and s1 is continued to read a sentence and match a frame . according to an order of numbers of the sentence cabins and cabin eyes , the sentence cabins or cabin eyes are searched in pairs one by one . with reference to the semantic match table , if word fields of language a and word fields of language b are not empty in records of the match table of the corresponding content and semantic content of texts of languages a and b is aligned , the content has become sense group strings . the content is fetched from the records in succession , and respectively stored in the corresponding language fields of the same record in the sense group database ( 109 ). for example , a sentence pair example of the frame example form after the foregoing processing is : 1 { dyslexia } first was recognized in 2 { europe } and 3 { the united_states } more than 4 { 80 years } ago . the sentence cabins or cabin eyes are searched in pairs one by one . with reference to the semantic match table , if word fields of language a and word fields of language b are not empty in records of the match table of the corresponding content and semantic content of texts of languages a and b is aligned , the content is determined to be sense group string components . for example , “ dyslexia ”, “ europe ”, “ united_states ”, and “ years ” are expressions of sense groups in different language texts , and are equivalence and unification of “ senses ” of characters , words , word combinations , or phrases of natural languages ; therefore , they are sense group strings , namely , sense group string components . then the sense group strings are saved to the corresponding language component fields in the sense group database ( 109 ) in records ( pairs ) one by one . the sense group database ( 109 ) includes a corresponding single string database and complex string database because sense group strings of a pinyin text are classified into single strings and complex strings . an ideographic text is stored in the single string database or complex string database with the strings of the pinyin text according to semantic content . before the storing , first , a search is performed , and the ideographic text is added if it is not found in the database for avoiding repetitions . there are single string fields of multiple languages such as “ english single string ”, “ chinese single string ”, and “ russian single string ” in the single string database , which are respectively used to store sense group single strings of corresponding languages . semantic content of single strings of multiple languages in a same record is same . for example , “ dyslexia ” and “ europe ”. there are complex string fields of multiple languages such as “ english complex string ”, “ chinese complex string ”, and “ russian complex string ” in the complex string database , which are respectively used to store sense group complex strings of corresponding languages . semantic content of complex strings of multiple languages in a same record is same . for example , “ united_states ”, “ lose_touch_with ”, and “ strike_a_balance ”. in the second round of semantic comparison and sense group string extraction , the labeled language sentences are used as a template . after the sense group string of the new language is obtained , the single string database or complex string database is searched by using the labeled language sense group string , and the sense group string is stored in the corresponding single string or complex string field of the new language in the same record . after all sense group strings after the semantic match ( semantic alignment ) in the sentence cabins and cabin eyes of the current sentence pair example are stored in the sense group database , the operation of semantic comparison of the current sentence pair example and extraction of ideographic components ends . step ( i ) is continued : reading a sentence and matching a frame ; reading a next sentence pair example , and continuing the foregoing operation . the foregoing method for extracting ideographic components is performed in orientation to bilingual sentences by using chinese and english as an example . semantic comparison is performed , and several ideographic components are identified and extracted . in each round of comparison , identification , and extraction , two languages a and b are selected ; language a is allocated to pinyin texts or is a language that is already compared , identified , and extracted . language b is allocated to ideographic texts , or may be allocated to pinyin texts , or is a new language . in the first round of comparison , identification , and extraction , a chinese and english bilingual sentence pair is selected as a core pair ; language a is english and language b is chinese . starting from the second round , one new language is added in each round ; the other one must be a language that is already compared , identified , and extracted . however , starting from the second round , operations of comparison , identification , and extraction are different . language a that is already compared , identified , and extracted is used as a template to identify and label sentence cabins and obtain sentence frames , and so on . for example , the new language in the second round is russian , which is language b ; language a is chinese that is already compared , identified , and extracted . a chinese and russian sentence pair is extracted : however , the chinese sentence is used to search the sentence frame database to obtain a matched sentence frame “[ 1 ]+ +[ 4 ]+ +[ 3 ]+[ 2 ]+ ”; the chinese sentence example is integrated into the frame to become a frame example form , for example , then , content in sentence cabins is fetched in succession according to the match table after the corresponding “ search , match , and label ” operation , for example , “ ” of a sentence cabin 1 is fetched . corresponding “ ” in russian is found according to the match table , and is labeled as a sentence cabin 1 , for example , 1 ? in the same way , “ ” of a sentence cabin 4 is fetched . corresponding “ ” in russian is found according to the match table , and is labeled as a sentence cabin 4 , for example , 1 ? in the same way , “ ” of a sentence cabin 3 is fetched . corresponding “ ” in russian is found according to the match table , and is labeled as a sentence cabin 3 , for example , 1 ? finally , “ ” of a sentence cabin 2 is fetched . corresponding “ ” in russian is found according to the match table , and is labeled as a sentence cabin 2 , for example , however , residual parts after the sentence cabins are removed are sentence frame components . the sentence frame of the new language russian is obtained : the sentence frame database is inquired by using the sentence frame of language a “[ 1 ]+ +[ 4 ]+ +[ 3 ]+[ 2 ]+ ?”, and then the “ russian sentence frame ” field of the record where the sentence frame of language a is located is filled with the newly obtained russian sentence frame “[ 1 ]+[ 2 ]+ +[ 3 ]+ +[ 4 ]+?” sentence frames of the three languages “ english , chinese , russian ” in the current sentence frame database are respectively : does +[ 1 ]+[ 2 ]+ as +[ 3 ]+ as +[ 4 ]+? comparison , identification , and extraction of other ideographic components are inferred by analogy . in the foregoing operation process of the method for extracting ideographic components , four types of ideographic components , namely , sentence frames , cabin models , sense group strings , and idioms , are extracted , and are stored in the corresponding sentence frame database , cabin model database , sense group database , and idiom database respectively . their features are as follows : ( 1 ) sentence frame components are residual frame parts of the sentence after the sentence cabins are removed . the sentence frame database is configured to store sentence frame components and has sentence frame codes , english sentence frame fields , chinese sentence frame fields , and russian sentence frame fields , where sentence frame fields of each language in a same record store sentence frames of corresponding languages , they have same semantic content , and the sentence frame codes are expressions of their semantic content and position . sentence frames of each language in a same record have same semantic content , which is decided by use of a language pair in each round of comparison , identification , and extraction . starting from the second round , a language is added in each round , and corresponding language component fields are added to the sentence frame database . a new sentence frame that is compared , identified , and extracted is stored in the corresponding language component field . the comparison , identification , and extraction method and software operation ensure that ideographic components in a same record have same semantic content . due to the features of the database , components of a same record are mapped mutually , including component fields and sentence frame codes of each language , and as long as one of them is searched out , content of the corresponding language component field may be fetched . ( 2 ) cabin model components are residual frame parts of the sentence cabins after the cabin eyes are removed . the cabin model database is configured to store cabin model components and has cabin model codes , english cabin model fields , chinese cabin model fields , and russian cabin model fields , where cabin model fields of each language in a same record store cabin models of corresponding languages , they have same semantic content , and the cabin model codes are expressions of their semantic content and position . a feature of the cabin model database is that language component fields of a same record in a same sentence frame database have same semantic content and are mapped mutually . ( 3 ) sense group string components are components for filling sentence cabins or cabin eyes . the sense group database is configured to store sense group string components and has sense group codes , english group string fields , chinese group string fields , and russian group string fields , where sense group string fields of each language in a same record store sense group strings of corresponding languages , they have same semantic content , and the sense group codes are expressions of their semantic content and position . a feature of the sense group database is also that language component fields of a same record in a same sentence frame database have same semantic content and are mapped mutually . ( 4 ) idiom components are a type of special sentence that cannot be divided into sentence frames and sentence cabins . the idiom database is configured to store idiom components and has idiom codes , english idiom fields , chinese idiom fields , and russian idiom fields , where idiom fields of each language in a same record store idioms of corresponding languages , they have same semantic content , and the idiom codes are expressions of their semantic content and position . a feature of the idiom database is also that language component fields of a same record in a same sentence frame database have same semantic content and are mapped mutually . ( 5 ) ideographic components are specific reflections of associating different language texts by using ideographs , and are semantic blocks having different sizes and different forms and structures . they are also equivalence and unification of ideographs of multilingual texts . in addition , ideographic components are semantic blocks that have different sizes and different structures and may be disassembled , assembled , and spliced . the ideographic components include sentence frame components , cabin model components , sense group string components , and idiom components , where the sentence frame database , cabin model database , sense group database , and idiom database jointly constitute an ideographic component database . the four sub - databases are independent of each other . ( 6 ) in identification and extraction starting from the second round , component fields of a new language should be added to the four sub - databases respectively in advance . ( 7 ) language text information processing is supported by the ideographic components and database thereof ; therefore , beneficial effects of associating different language texts by using ideographs and overcoming “ semantic barriers ” by using language text information processing may be achieved . multiple scenarios of language text information processing may be supported . described by using a visualized language , sentence frame components are like a chassis of a car , and just enough space and connecting parts are reserved for the driver &# 39 ; s cab , wheels , power machine , oil supply machine , and so on . the cabin model components are like the driver &# 39 ; s cab , and further include other small machines and parts . the sense group string components are like wheels , other types of small machines , assemblies , components , and so on , and may be assembled in any position as required . the idiom is a special type of minicar having only features of a basic car , even a jinriksha and a handcart , and so on . ii . a method for performing interactive translation of machine translation and human proofreading based on ideographic components with reference to fig2 , which is a flowchart of interactive translation of machine translation and human proofreading , by using english - to - chinese translation as an example , the following further describes the method for performing interactive translation of machine translation and human proofreading . a source language file to be translated is read ( 201 ), and saved to a buffer . then steps of the following four modules are performed : ( i ) reading a sentence , matching a frame , and integrating a source language sentence into the frame ( 202 ). a source language sentence is read , a sentence frame database is searched by using the source language sentence , and a sentence frame match operation same as above is performed . oliver twist was born in workhouse ; there were no aunts , no sisters , no cousins , no grand_mothers . english words and chinese characters are fetched one by one from the current sentence example from left to right , a frame header field ( in english , the first word or symbol of a sentence frame word string is included ; in chinese , the first word is included ) in a sentence frame word string table ( including a frame header field , a sentence frame field , and a sentence frame code field ) is searched out , and a search result is saved to a temporary table . then content of the temporary table is fetched from the records in succession , and sentence pair examples are inquired by using sentence frame word segments . if each segment of the sentence frame word string may be found in the sentence pair examples and sequences thereof in sentence frames are the same , those sentence frames are matched sentence frames . then a sentence frame of the corresponding language is fetched according to the sentence frame code field of the sentence frame word string table . the sentence frame code is made up of a sentence frame database flag and a record number . other index tables are inferred by analogy . in this example , the source and target language sentence frames are fetched from a sentence frame database according to the sentence frame code field as follows : “[ 1 ]+ +[ 2 ]+; +[ 3 ]+, +[ 4 ]+, +[ 5 ]+, +[ 6 ]+.” then the source language sentence is integrated into the source language sentence frame strictly according to cabin numbers . “ integrating strictly according to cabin numbers ” means that the first sentence frame word segment “ was born in ” in the example matches the corresponding segment “ was born in ” in the sentence example , and that the sentence frame word segment “; there were no “ matches the corresponding segment ”; there were no ” in the sentence example , such as the “ bold ” parts : oliver twist was born in workhouse ; there were no aunts , no sisters , no cousins , no grand_mothers . other parts ( italic ) than the corresponding segments in the sentence example are respectively arranged in corresponding sentence cabins ( that is , in a frame example form ), for example , “ oliver twist ” is arranged in a sentence cabin [ 1 ], and “ workhouse ” is arranged in a sentence cabin [ 2 ], “ aunts ” is arranged in a sentence cabin [ 3 ], and so on , in a source language sentence frame example combination form . for example , 1 { oliver twist } was born in 2 { workhouse }; there were no 3 { aunts }, no 4 { sisters }, no 5 { cousins }, no 6 { grand_mothers }. after the source language sentence is integrated into the source language sentence frame strictly according to cabin numbers , cabin detection is performed . if a cabin is a sentence cabin with a model , a cabin model database is searched , the cabin is integrated into the cabin model and incorporated into the sentence frame , so that it is in a source language sentence frame example combination form . the step ends . ( ii ) transferring content of sentence cabins or cabin eyes ( 203 ). content of sentence cabins or cabin eyes is fetched in succession from the source language sentence frame example form , and transferred to corresponding sentence cabins or cabin eyes of a target language sentence frame to derive a source and target language transition form . using the foregoing sentence cabin including a model as an example , a source language frame example form thereof is as follows : 1 { the american } 2 { economic } machine is , organized around 3 { a basically private - enterprise }, 4 { market - oriented economy } in which 5 { consumers } largely determine 6 { what shall be produced } by 7 {( 2301 ) spending their money in 1 [ the marketplace ] for those 2 [ goods and services ] that 3 [ they want most ]}. corresponding sentence cabins or cabin models of a target language sentence frame are as follows : { 1 } { 2 } { 3 } { 4 } { 2 } , { 5 } 7 {( 2301 ) [ 1 ] [ 3 ] [ 2 ] { 6 }. then the content of the sentence cabins or cabin eyes is fetched in succession from the source language sentence frame example form , and transferred to the corresponding sentence cabins or cabin eyes of the target language sentence frame . for example , content “ the american ” of a sentence cabin 1 is fetched and transferred to a corresponding sentence cabin 1 “{ 1 }” of the target language sentence frame ; content “ economic ” of a sentence cabin 2 is fetched and transferred to a corresponding sentence cabin 2 “{ 2 }” of the target language sentence frame ; . . . ; content “ the marketplace ” of a cabin eye 1 in a sentence cabin 7 is fetched and transferred to a corresponding cabin eye 1 “[ 1 ]” of a sentence cabin 7 of the target language sentence frame , and so on , to derive a source and target language transition form : 1 { the american } 2 { economic }, 3 { a basically private - enterprise } 4 { market - oriented economy )} , 2 { economic } , 5 { consumers } 7 {( 2301 ) 1 [ the marketplace ] 3 [ ] 2 [ goods and services ] 6 { what shall be produced }. therefore , a source and target language transition form is derived . the step ends . ( iii ) saving inquiry items and pre - selecting and providing a target language sentence to be corrected ( 204 ). word strings of the source language are fetched one by one from the sentence cabins or cabin eyes in the source and target language transition form , and a sense group database is inquired . if no word spacing exists in an ideographic text , the sense group database is inquired by using possible left - to - right arrangements , and inquiry items of the word strings of the two languages are saved to a correcting table . the correcting table includes at least a word string segment field , a search string field , an explanation field , and a string header field . continued from the foregoing example , “ american ” is fetched , the sense group database is inquired , and “ ”, “ ”, “ ”, “ ”, and “ ” are obtained ; “ american ” is saved to the search string field ; “ ”, “ ”, and so on are saved to explanation fields : the word string segment field is filled with 1 ; and the string header field is filled with 8 ( including a space and occupying the eighth character position ). then “ economic ” is fetched and saved to the search string field , the sense group database is inquired , and “ ”, “ ”, “ ”, and so on are obtained and saved to explanation fields ( three records are added in the correcting table again ); the word string segment field is filled with 2 ( they are the second segment ); the string header field is filled with 22 , and so on . a search is performed by using a pre - selecting module ( 402 ). if a record is reselected , it is transposed to the header of the word string segment in the correcting table . in the foregoing example , before a machine operates the pre - selecting module , the target language sentence is as follows ( note italic words ): 1 { } 2 { } 3 { } 4 { } 2 { } , 5 { } 7 {( 2301 ) 1 [ ] 3 [ ] 2 [ ] } 6 { }. in the pre - selecting module ( 402 ), an experience - based word database ( 405 ) ( including english string fields and chinese explanation fields ) and a chinese word order database ( 408 ) ( including an original order field and a corrected order field ) need to be searched . the sentence cabin 1 “ american ” has a reselected record of “ ” in records of the experience - based word database ( 405 ). in this case , the fourth record at “ ” in the correcting table is the first word string segment , and the segment header is “ ”. therefore , “ ” is replaced with “ ” ( because only the segment header record is provided finally ). similarly , “ basically ” in a sentence cabin 3 has a reselected record of “ ”; content of a cabin eye 3 of a sentence cabin 7 has a record of a corrected order of “ ” in the chinese word order database ( 408 ); after the operation in the pre - selecting module and after the corresponding sentence cabins and cabin eyes are corrected automatically , a target language sentence to be corrected that reserves flags and numbers of sentence cabins and cabin eyes after the pre - selection is provided ; and the sentence to be corrected is displayed ( 416 ) as follows : 1 { } 2 { } 3 { } 4 { } , 2 { } , 5 { } 7 {( 2301 ) 1 [ ] 3 [ ] 2 [ ] } 6 { }. the corresponding source language reference sentence is : 1 { the american } 2 { economic } machine is , organized around 3 { a basically private - enterprise }, 4 { market - oriented economy } in which 5 { consumers } largely determine 6 { what shall be produced } by 7 {( 2301 ) spending their money in 1 [ the marketplace ] for those 2 [ goods and services ] that they want most }. while the sentence to be corrected is displayed and provided , command buttons “ return ”, “ follow - up ”, “ move left ”, “ move right ”, “▴”, “ λ ”, and “ rhetoric ”, and a corresponding source language reference sentence are displayed ; and a preparation is made for accepting a user &# 39 ; s correcting operation . the step of this module ends . all the steps in modules ( i ) to ( iii ) are completed in a completely automatic state , and are a “ machine translation ” part in the method title “ a method for performing interactive translation of machine translation and human proofreading ”. next , the step of module ( iv ) is a “ human proofreading ” part , where interactions in human proofreading ensure that a fast and convenient use effect is achieved . still as shown in fig3 , which is a flowchart of a semantic content correcting module , after the operation in the step of the foregoing module , the target language sentence to be corrected , button , and source language reference sentence are provided ( 301 ), and a preparation is made for correcting semantic content . when the user reads the target language sentence to be corrected and the corresponding source language reference sentence , a correcting operation is started . the correcting module of the machine performs a semantic content correcting operation by using the correcting table , and the self - leaming module ( 401 ) interacts with the correcting module to learn and memorize man - machine interactions in the correcting process and provide data for the pre - selecting module . ( a ) replacing impropriate word strings ( 302 ): for example , the sentence to be corrected that is read by the user and the corresponding source language reference sentence are as follows : when the user considers that a word string “ ” in the sentence to be corrected is appropriate , the user clicks it . the machine searches the correcting table , and displays a drop - down list providing all related inquiry items as options . the search string field and string header field are inquired according to a clicked word string and character positions in the sentence to be corrected , and compliant records such as “ , , , ” are provided in a drop - down list . when an option in the list is clicked by the user , for example , when “ ” is clicked , the current impropriate word string “ ” is replaced with “ ”; content of the two records “ ” and “ ” in the correcting table is interchanged ; because the length of “ ” is not equal to the length of “ ”, the value of the “ string header ” field needs to be recorded after the modification . after the “ return ” button is clicked , the foregoing correction information is recorded in the experience - based word database , so that it is used for a search by the pre - selecting module . finally , the machine returns and performs an operation of translating a next sentence . ( b ) segmenting continuous sentence cabins ( 303 ): when continuous sentence cabins that cannot be segmented automatically for lack of reference are encountered , the sentence cabins are provided for segmentation and the user &# 39 ; s intervention . for example , when continuous sentence cabins include two word strings , the two sentence cabins respectively take one word and are segmented automatically . for another example , two sentence cabins are continuous , and one of the sentence cabins is a repetitive sentence cabin . by referring to the other one of the repetitive sentence cabins , a same part in the repetitive sentence cabins is divided out of the continuous sentence cabins , and the residual part belongs to the other one of the continuous sentence cabins . for example , the operation on the sentence to be translated “ when will he go there , tomorrow or some_other_day ?” pauses , and continuous sentence cabins “ 1 { 2 { he go there }” appear and cannot be segmented for lack of reference ; therefore , “ continuous sentence cabins . please click a segmentation point :” is displayed : apparently , “ he go there ” should be segmented into “ he ” and “ go there ”, which are respectively put into [ 1 ]+ +[ 2 ]. when “ he go there ” is clicked , the clicked point is used as a segmentation point to separate content of the two sentence cabins , so that the sentence becomes : ( c ) intervening and selecting another sentence frame ( 304 ): when encountering an incorrect selection of a sentence frame , such as uneven , incomplete , or stacking sentence cabins or cabin eyes , or when the user does not approve the current translated sentence and clicks the “ follow - up ” button , the machine provides multiple matched sentence frames as options , reintegrates the sentence into a sentence frame selected by clicking , and continues to perform the operation in s6 . for example , a sentence to be translated is : all content of the reference sentence is stacked in one sentence cabin . at least “ one sentence includes two parts : a sentence frame and a sentence cabin ” is not supported . the sentence frame selected automatically is incorrect . the “ follow - up ” button is clicked by the user , and multiple matched sentence frames are provided as options . after the user selects another sentence frame , the operation is continued to provide the sentence to be corrected and the corresponding source language reference sentence : after the foregoing command button is clicked by the user , subsequent operations are judgment and follow - up ( 313 ). ( d ) adding a sense group string ( 305 ): when another word string is selected to replace an impropriate word string and the sentence becomes incomplete , the user &# 39 ; s addition of a sense group string by using a sense group alignment method such as extending senses of words or adding characters or words ahead or behind is accepted , and the added string is used to make a replacement , and added to a corresponding language component field of the sense group string . for example , a sentence to be translated is : when the user clicks “ doctors ”, no option is found in the correcting table . when the user selects doctors to inquire a dictionary , a prompt “ doctors is a plural noun or a third - person singular verb ” is provided . the method specifies that all inflectional forms of words are recorded as new words . a sense group string “ doctors ” and “ ” entered by the user is accepted as a new sense group string and saved to the sense group database . meanwhile , the sentence to be corrected is replaced with : after the foregoing command button is clicked by the user , subsequent operations are judgment and follow - up ( 313 ). ( e ) composing and selecting a complex word string ( 306 ): when another word string is selected to replace an impropriate word string and the sentence becomes incomplete , the user &# 39 ; s addition of a complex word string by using a method of composing a complex word or reselecting a complex word is accepted , and the added string is used to make a replacement , and added to a corresponding language component field of a complex word database of the sense group database . an automatically provided sentence to be corrected and a corresponding source language reference sentence are : when the user clicks word strings in one of the two sentence cabins , the user does not select an option listed in the correcting table , but uses a drag method to select “ before eating ”. a complex string “ ” composed by using the word strings by using a method of composing a complex word by the user is accepted . herein the word strings “ ” are replaced and the complex string is added to the complex word database . then the user uses the drag method to select “ during the night ”, and a complex word “ during the night ” is automatically inquired and provided . the user &# 39 ; s click and selection are accepted . in this case , the sentence to be corrected is corrected as follows : after the foregoing command button is clicked by the user , subsequent operations are judgment and follow - up ( 313 ). ( f ) word order of a sentence cabin ( 307 ): when the word order of a sentence cabin of a translated sentence is incorrect , the user &# 39 ; s click on a string and click on the “ move left ” or “ move right ” button are accepted , and then the clicked string is shifted forward or backward by one string position . doctors have been able to help lessen the pain of ulcers . an automatically provided sentence to be corrected and a corresponding source language reference sentence are : 1 { doctors } have been able to help 2 { lessen the pain of ulcers }. if the user clicks “ ” and then clicks the “ move right ” button twice consecutively , the word is shifted right twice , and the sentence to be corrected is changed to : then the user clicks the “ move right ” button after clicking “ ”, and the sentence to be corrected is corrected as follows : when the user clicks the “ return ” button , first it is determined that the user changes the word order by using the “ move left ” or “ move right ” button , and the self - learning module is started . content before and after the movement in the currently moved sentence cabin is saved to the “ chinese word order ” database . then the machine returns . ( g ) replacing words ( 308 ): when multiple continuous strings are impropriate and cannot be selected by clicking , when the user selects a string by using a drag operation , enters another word string in a word replacement position , or edits the string , or makes it empty , and then dicks the “ λ ” button , the machine replaces the former with the latter . alfred herman , he shared the 1911 nobel peace prize for his work toward world peace . an automatically provided sentence to be corrected and a corresponding source language reference sentence are : 1 { }, 2 { } 4 { } , 3 ( 1911 peace prize }. 1 { alfred herman }, 2 { he } shared 3 { the 1911 nobel peace prize } for his work toward 4 { world peace )}. when the user considers that “ peace prize ” is inappropriate and selects them by using a drag operation , the machine displays them in a text box like “ string selection ” and “ word replacement ”, and accepts the edited “ ”. when the “ λ ” button is clicked , the former is replaced with the latter , and the sentence to be corrected is corrected as follows : after the foregoing command button is clicked by the user , subsequent operations are judgment and follow - up ( 313 ). ( h ) rhetoric ( 309 ): when a rhetoric phenomenon cannot be processed by using the foregoing listed steps , the user &# 39 ; s dick on the “ rhetoric ” button is accepted , and then the current sentence to be corrected is copied to an editing box , and the user &# 39 ; s rhetoric operation performed by using an editing method is accepted . for example , a sentence to be translated or a rhetoric phenomenon after processing in other listed steps is as follows : dickens &# 39 ; language , at once rich colourful and varied , is like fine and sensitive musical instrument . an automatically provided sentence to be corrected and a corresponding source language reference sentence are : 1 { dickens &# 39 ; language }, at once 2 { rich colourful } and 3 { varied }, is like 4 { fine and sensitive musical instrument }. when the user clicks the “ rhetoric ” button , the sentence to be corrected is copied to the editing box , and the user &# 39 ; s rhetoric operation performed by using an editing method is accepted . after the operation , the target language sentence to be corrected is : in addition to the foregoing functions , the “ return ” command button is further used to scan an editing box that is specially set for rhetoric . when the editing box is not empty , content of the box is fetched and returned ; otherwise , the sentence to be corrected is fetched and returned . ( j ) adding a quantifier ( 311 ): in english - to - chinese translation , because there is no quantifier in english but there are quantifiers in chinese , when necessary , a quantifier needs to be added to the sentence to be corrected , and the machine accepts the user &# 39 ; s click in a position in which addition is needed in the sentence to be corrected , and searches for a central noun after a quantity string that is closest to the clicked point ; when the “▴” button is also clicked , the machine searches a quantifier database by using the central noun , fetches the corresponding quantifier , and adds it to the sentence to be corrected ; if no quantifier is found in the quantifier database , the machine provides a dialog box , accepts the entered quantifier , adds it to the sentence , and adds it to the quantifier database . for example , a sentence to be translated is : on apr . 24 , 1970 . china successfully launched its first man - made earth satellite . an automatically provided sentence to be corrected and a corresponding source language reference sentence are : 1 { 24 }, 2 { 1970 , } 3 { }. 1 { on april 24 }, 2 { 1970 , china } successfully launched its 3 { first man - made earth satellite }. the user selects a central noun after a number string or a quantity string by using a drag operation . for example , the user selects “ , and the machine displays them in “ string selection ” and “ word replacement ”. when the user clicks the “▴” command button , the quantifier database is searched by using the central noun (“ ” herein ), and a corresponding quantifier “ ” is fetched and added to the sentence to be corrected . in this case , the sentence to be corrected is changed to : 2 { 1970 } 1 { 24 }, 3 { } 4 { }. if the quantifier is not found in the quantifier database , a dialog box is provided , saying “ the quantifier is not found . the quantifier may be added in a ‘ quantifier / noun ’ form in word replacement .” in this example , “ ” may be entered . after the foregoing command button is clicked by the user , subsequent operations are judgment and follow - up ( 313 ). the foregoing steps a - h are unrelated to the types of language texts and have common features , and may appear in a bidirectional translation process of multiple languages , for example , a bidirectional translation process of english - to - chinese translation or chinese - to - english translation . the step j are related to the types of language texts and used in translating english into chinese or translating other languages into chinese . hereinafter , the stepsl and k are further related to the types of language texts . the step i are used in translation of ideographic texts without word spacing , for example , chinese - to - english translation . the step k are used in chinese - to - english translation . j - k have individual features , which are set according to specific languages . english - to - chinese translation is used as an example for description above . hereinafter , i and k occur in a chinese - to - english translation process . therefore , chinese - to - english translation is hereinafter used as an example for description accordingly . ( 1 ) converting cabins ( 310 ): in chinese - to - english translation , the machine accepts the users click on content of a sentence cabin or a cabin eye , searches for all inquiry items included in the current sentence cabin or cabin eye in the correcting table , provides them in a list , waits for the user to sequentially click and select for multiple times , and uses them to replace the content of a corresponding sentence cabin or cabin eye in the sentence to be corrected . an automatically provided sentence to be corrected and a corresponding source language reference sentence are : 1 { essentially }, a 2 { theory } is an 3 { abstract }, 4 { } of what is conceived to be 5 { reality }. the sentence to be corrected includes four sentence cabins , where three sentence cabins have been translated into english , and only a sentence cabin 4 reserves content “ 4 { }” of the source language sentence cabin . when the user clicks the cabin content “ ”, in the process of inquiring the sense group database and generating the correcting table , because possible left - to - right arrangements of an ideographic text without word spacing are used as word strings to inquire the sense group database , all inquiry items are saved to the correcting table . “ ” is segmented into chinese word strings such as “ ”, “ ”, “ ”, “ ”, and “ ”, and the inquiry items include them and english explanations related to them , so that the user selects them sequentially according to english habits . herein the user should first select “ symbolic ”, and then select “ representation ”. then processing of the current sentence cabin is completed . the current sentence to be corrected is : 1 { essentially }, a 2 { theory } is an 3 { abstract }, 4 { symbolic representation } of what is conceived to be 5 { reality }. regardless of whether there are other corrections , the machine detects whether the foregoing command button and the provided related box and table are clicked by the user , and determines whether to perform subsequent operations of judgment and follow - up ( 313 ) accordingly . ( k ) adding articles and other words ( 312 ): in chinese - to - english translation , because there are no articles in chinese and verbs to / be and to / have and so on are not distinguished , these words need to be added in chinese - to - english translation ; when the machine provides the target language sentence to be corrected that reserves flags and numbers of sentence cabins , the machine has displayed “ a / an ”, “ the ”, “ to / be ”, “ to / have ”. and “###”; when one of them is clicked ( except “###”, which is an end flag ) and the sentence to be corrected is also clicked , the machine uses one of them to add a word string of an appropriate form in the clicked position in the sentence to be corrected . an automatically provided sentence to be corrected and a corresponding source language reference sentence are : the machine inquires the sense group database by using possible arrangements of “ ”, and saves all inquiry items to the correcting table for the user to make a selection . herein the user selects “ ” and “ tired ”. in this case , the sentence to be corrected is changed to : this obviously does not comply with requirements of english . the user clicks “ to / be ” in “ a / an the to / be to / have ###” listed under “ add articles and other words ”, and then clicks the space in “ we tired ”. the machine determines that an operation of “ adding articles and other words ” needs to be performed herein , and determines , according to a requirement of “ to / be ”, that a verb “ are ” should be inserted herein . then the current sentence to be corrected is changed to : regardless of whether there are other corrections , the machine detects whether the foregoing command button and the provided related box and table are clicked by the user , and determines whether to perform subsequent operations of judgment and follow - up ( 313 ) accordingly . the steps that need to be corrected are listed and described above . another case is that the provided sentence to be corrected is completely correct and that the user clicks the “ return ” button without clicking any one of the foregoing buttons and related displayed page controls , that is , in this case , the provided sentence to be corrected is completely correct and does not need to be corrected . with the use of the method , more and more such cases will occur . it should be noted additionally that , all the sentences to be corrected that are mentioned above are provided in forms of target language sentences to be corrected that reserve flags and numbers of sentence cabins and cabin eyes . when the “ return ” command button is clicked , the machine retums , and all these flags and numbers of sentence cabins and cabin eyes and unnecessary spaces are discarded , as in a conventional manner . for example , “ 1 { we are tired }, as anyone can see .”; “ 2 { 1970 } 1 { 24 }, 3 { } 4 { }.” is changed to : “ we are tired , as anyone can see ”. 1970 24 , , “ which is returned and provided in a translation text box . finally , a target language text is generated and output ( 206 ).” a software machine generated for implementing the present invention may be operated and implemented in stand - alone or networked computers such as an existing mid - range computer , a minicomputer , a microcomputer , a supercomputer , a notebook computer , and a palmtop computer . it may be operated and implemented in various computer networks , and in particular , on the internet . it may also be operated and implemented in apparatuses such as a “ personal digital assistant ” pda ( personal digital assistant ), a tablet computer , and a mobile phone . a product in which the present invention is implemented may be applied in scenarios of work , study , entertainment , tourism , and so on where communication with people of other languages is required ; and may be used in scenarios of homes , organizations , schools , and every industry or trade where foreign languages are involved .	6
refer to fig1 , it is a flowchart showing a fabrication process according to a preferred embodiment of the invention . firstly , a metal - chalcogenide precursor containing benzyl or benzyl derivative is synthesized ( step s 101 ), wherein the metal - chalcogenide precursor containing benzyl or benzyl derivative has the general formula of ( r 1 r 2 r 3 r 4 r 5 — c 6 h 3 — ch 2 —) nh - 2i m h x i ; wherein r 1 , r 2 , r 3 , r 4 , and r 5 are each independently a functional group , m denotes an n - valent metal and n is an integer of 1 - 6 , x denotes a chalcogen element , h is an integer of 1 - 10 , and i is an integer of 0 - 30 ; wherein the r 1 - 5 groups are selected from hydrogen , aromatic , ester , ether , carboxylic acid , sulfonic acid , aldehyde , hydroxyl , ketone , imine , amide , methyl or ethyl group , and a branched or cyclic aliphatic group containing 3 to 6 carbons , and the metal is germanium ( ge ), antimony ( sb ), tin ( sn ), lead ( pb ), bismuth ( bi ), gallium ( ga ), indium ( in ), or thallium ( ti ). and then , the precursor is dissolved in a solvent to produce a precursor solution ( step s 103 ), wherein a chalcogen element or compound can be added to the precursor solution to adjust the molar ratio of metal ion to chalcogen therein ; wherein the chalcogen element is sulfur , selenium , or tellurium , or a mixture thereof , and the solvent may be selected from aromatics , aliphatics , esters , ketones , alcohols , amides , amines , imines , sulfonamides , or a mixture thereof . thereafter , the precursor solution is pattern - coated on a suitable substrate in a coating manner ( step s 105 ), such as roller coating , ink jet printing , screen printing , or imprinting , and the like . after the substrate is dried through a hot plate , a curing process is performed to form a patterned active layer film on the substrate ( step s 107 ) for use in a semiconductor element . the curing process can be performed by direct pattern , ultraviolet curing , or thermal curing to cure the existing patterned region ; and the semiconductor element may be , for example , an active element , thin film transistor , solar cell , radio - frequency identification element ( rfid ), integrated circuit , or optical communication element , and the like . refer to fig2 , it is a flowchart showing a fabrication process according to another preferred embodiment of the invention . firstly , a metal - chalcogenide precursor containing benzyl or benzyl derivative is synthesized ( step s 20 1 ), wherein the metal - chalcogenide precursor containing benzyl or benzyl derivative has the general formula of ( r 1 r 2 r 3 r 4 r 5 — c 6 h 3 — ch 2 —) nh - 2i m h x i ; wherein r 1 , r 2 , r 3 , r 4 , and r 5 are each independently a functional group , m denotes an n - valent metal and n is an integer of 1 - 6 , x denotes a chalcogen element , h is an integer of 1 - 10 , and i is an integer of 0 - 30 ; wherein the r 1 - 5 groups are selected from hydrogen , aromatic , ester , ether , carboxylic acid , sulfonic acid , aldehyde , hydroxyl , ketone , imine , amide , methyl or ethyl group , and a branched or cyclic aliphatic group containing 3 to 6 carbons , and the metal is germanium ( ge ), antimony ( sb ), tin ( sn ), lead ( pb ), bismuth ( bi ), gallium ( ga ), indium ( in ), or thallium ( ti ). and then , the precursor is dissolved in a solvent to produce a precursor solution ( step . s 203 ), wherein a chalcogen element or compound can be added to the precursor solution to adjust the molar ratio of metal ion to chalcogen therein ; wherein the chalcogen element is sulfur , selenium , or tellurium , or a mixture thereof , and the solvent may be selected from aromatics , aliphatics , esters , ketones , alcohols , amides , amines , imines , sulfonamides , or a mixture thereof . thereafter , the precursor solution is non - pattern - coated on a substrate in a coating manner ( step s 205 ), such as spin coating , roller coating , ink jet printing , slot die coating , screen printing , or imprinting , and the like . after the non - pattern coating , an active layer thin film can be formed , for example , through the following two ways . one is that after the substrate is dried through a hot plate , a curing process is performed by photo or thermal curing to directly cure the whole non - pattern coated region ( step s 207 ), and then photoresist and etching is utilized to remove unwanted metal - chalcogenide portion , forming a patterned active layer film ( step s 209 ). the other is that after the substrate is dried through a hot plate , a curing process is performed by a photo - mask in combination with laser or ultraviolet curing to only cure a desired pattern region ( step s 211 ), and then a developer is utilized to remove uncured metal - chalcogenide precursor portion , forming a patterned active layer thin film ( step s 213 ). finally , the patterned active layer thin film is applied to a semiconductor element , such as , active element , thin film transistor , solar cell , radio - frequency identification element ( rfid ), integrated circuit , or optical communication element , and the like . refer to fig3 , it is a sectional view showing the use in a bottom - gate thin - film transistor according to the invention . in a presently common bottom - gate thin - film transistor structure , an active layer thin film is formed by plasma enhanced chemical vapor deposition ( pecvd ) to deposit amorphous si on a gate insulator , and then coating photoresist is performed by spin coating , and after exposure and development , a pattern is obtained by etching . and in the present invention , a metal - chalcogenide precursor solution is pattern - coated on a gate insulator 3 formed on a substrate 1 , then a photo or thermal curing ( laser direct pattern ) is performed to fabricate a semiconductor layer 4 of an active layer thin film and a positively charged semiconductor layer 5 of an active layer thin film having material nature close to that of amorphous silicon , which are insulating for a first conductive layer 2 through the gate insulator 3 . a passivation layer 7 is further set on a second conductive layer 6 to insulate from outside , and a third conductive layer 8 is used to connect with outside . in addition , for the positively charged semiconductor layer 5 of an active layer thin film , after being non - pattern coated and cured , unwanted pattern region is removed by laser direct pattern . non - limiting exemplifications below are only used to further illustrate embodiment aspects of the present invention . refer to fig4 , it is a flowchart showing a synthesis process of a tin sulfide precursor containing benzyl group according to an embodiment of the invention . it can be seen in the fig4 that , a dibenzyl tin dichloride / thf solution ( step s 401 ) is firstly take , and then added drop - wise to anhydrous sodium sulfide / thf solution with magnetic stirring at 30 ° c ., and after this , the mixture solution is continually stirred for thorough mixing to react ( step s 403 ). subsequently , the reaction solution is poured into water , and extracted with diethyl ether ; repeat three times ( step s 405 ). the extract is concentrated under reduced pressure and filtrated to obtain a solid product ( step s 407 ). and then , the solid product is dried in vacuum at room temperature to synthesize the tin sulfide precursor containing benzyl group ( 2 , 2 , 4 , 4 , 6 , 6 - hexabenzyl cycloytristannasulfane , ( bn 2 sns ) 3 )( step s 409 ). refer to fig5 , it is a flowchart showing a preparation process of a tin - chalcogenide active - layer film according to an embodiment of the invention . firstly , the tin sulfide precursor synthesized in the fig4 is taken , mixed simultaneously with chalcogenide dibenzyl disulfide , dibenzyl diselenide , and pyridine as a solvent , and stirred on a hot plate at 60 ° c . until they are completely be dissolved . after that , the mixture solution is filtrate through a filter , obtaining a precursor solution ( step s 501 ). subsequently , the precursor solution is spin - coated on a substrate ( step s 503 ), dried with a hot plate ( step s 505 ), and charged into an oven under nitrogen to perform thermal curing ( step s 507 ). repeat ( steps s 503 to s 507 ) three times , to provide the tin - chalcogenide active - layer film ( step s 509 ). refer to fig6 , it is a flowchart showing a synthesis process of a tin sulfide precursor containing benzyl derivative according to another embodiment of the invention . it can be seen in the fig6 that firstly a di ( 4 - methylbenzyl ) tin dichloride )/ thf solution is taken ( step s 601 ), and then added drop - wise to anhydrous sodium sulfide / thf solution with magnetic stirring at 30 ° c ., and after this , the mixture solution is continually stirred for thorough mixing to react ( step s 603 ). subsequently , the reaction solution is poured into water , and extracted with diethyl ether ; repeat three times ( step s 605 ). the extract is concentrated under reduced pressure and filtrated to obtain a solid product ( step s 607 ). and then , the solid product is dried in vacuum at room temperature to synthesize the tin sulfide precursor containing benzyl derivative ( 2 , 2 , 4 , 4 , 6 , 6 - hexa ( 4 ′- methyl - benzyl ) cycloytristannasulfane , ( ch 3 — bn 2 sns ) 3 )( step s 609 ). refer to fig7 , it is a flowchart showing a preparation process of a tin - chalcogenide active - layer film according to another embodiment of the invention . firstly , the tin sulfide precursor synthesized in the fig6 is taken , mixed simultaneously with chalcogenide dibenzyl disulfide , dibenzyl diselenide , and pyridine as a solvent , and magnetically stirred until they are completely be dissolved . after that , the mixture solution is filtrate through a filter , obtaining a precursor solution ( step s 701 ). subsequently , the precursor solution is spin - coated on a substrate ( step s 703 ), dried with a hot plate ( step s 705 ), and charged into an oven under nitrogen to perform thermal curing ( step s 707 ), to provide the tin - chalcogenide active - layer film ( step s 709 ). in conclusion , with the technical approaches above , the present invention can not only achieve the purposes of reduced equipment cost and simplified process , but also further provide enhanced quality : in the precursor solution of the invention , various properties of the active layer thin film , such as band gap value and mobility etc ., can be adjusted by adding other compounds for doping ; and it can be well verified that these properties have favorable benefits for reducing starting voltage and improving whole quality . the invention is different from conventional technologies either in materials or in fabrication manner , is considerably valuable for industry application , and conforms to the requirements of novelty and inventive step . but , the foregoing general descriptions are only illustrative and not to limit the present invention . it will be apparent to those skilled in the art that various modifications and variations can be made without departing from the scope of the invention , which fall within the scope of the following claims .	7
the present invention relates to the manipulation of pipettes , as well as a number of its applications . for the purpose of illustration , the drawings as well as the description will generally refer to the apparatus addressing this solution as a liquid handling android . however , the means disclosed in this invention are equally applicable to more general embodiments in the field of liquid handling . the global structure of a liquid handling android comprises few elements , all of which have a given functional role in the architecture . in essence , a liquid handling android operates above a certain deck , that could include or not the android base itself . the deck could either be a physical part , soft or rigid , either a virtual region without delimitations — for example belonging to a laboratory bench . the deck could also be the physical assembly of smaller units , called blocks , that combine together in order to form a larger operating surface . a liquid handling android body — also referred to as base — provides the physical support to the arm , and possibly may comprise additional hardware like power chord connector , general switch , illumination , twister , settings camera , arm fixation , usb hub , tip waste tray , pipette rack , lifting handle . most importantly , its purpose is providing a certain stable anchor to the arm movement . the arm constitutes the main electromechanical element : it generates movement of the hand in space , mainly moving over a two dimensional surface but also capable of lifting and descending the pipette in order to perform the desired pipette action . the arm is attached to the body and could either comprise a hand , or be connected to a hand . the hand constitutes the part of the body coming in contact with the pipette , and with the optional ability of grabbing and depositing pipettes onto the pipette rack . additionally , the hand may contain a hand camera , the functionality of manipulating the pipette knob for the purpose of aspiration and dispensing , the functionality of tip ejection and the functionality of actuating the pipette for the purpose of setting a desired volume . the system is complemented by a software interface , whose purpose comprises controlling the movements of the arm , the actions of the hand , communicating with the cameras and processing the images , and above all managing all the interaction with the user for programmability purposes and also for reporting purposes . a possible liquid handling android can be made as described in fig1 . the body 101 could be an injection moulded polymeric structure , either monolithic or in various parts , including active components ( like electronics and cameras ) and passive components like a weight ballast ( solid or liquid - filled ), preferably positioned in the lower part 104 . in some embodiments , the body could include a foot ( not shown ) meant to provide additional stability . in other embodiments the body could be positioned onto a laboratory bench but , by hosting batteries and interfaces , could also be designed to be used in other environments , like in the field or in portable implementations . in the figure , the body hosts a ballast 104 , a receptacle for a removable tip tray 103 , a body camera in location 102 with the purpose of volumetric setting and possibly with the purpose of deck area monitoring and inspection for intrusion detection , a plurality of pipette slots 121 , in the form of receptacles or hanging fixtures or magnetic holders or similar designed to host pipettes like the one indicated by 105 . the body can include a lifting handle like the one described in 108 , and mechanical elements like the one indicated in 109 making the interaction with the pipette easier , for example by allowing an easy access the ejection button for the tip . the body can include a twister 122 , defined as the actuator capable of setting the pipette volume . typically , this operation is performed by twisting the knob of the pipette , but it could also be achieved by electronic means for electronic pipettes — for example remote bluetooth communication or physical electrical links . it should be noted that additional electronics accessories could improve the advantages of the system : for example , a temperature or pressure or humidity sensor , possibly connected to a usb hub and read directly from the software interface , could allow improving the calibration of the pipettes by integrating and correcting for this information . the deck area 106 defines the operating surface of the liquid handling android , being larger , smaller or equal than the operating range of the arm . the deck area could have a circular shape , a rectangular shape or similar . preferably the deck has a shape making intuitive to the user the correct orientation . the deck could be a virtual region , for example delimited by simple illumination , but also a soft pad ( for example , a silicon pad that can be easily rolled above itself to reduce its size and recover a flat conformal shape when positioned onto a bench ), or a rigid metallic or polymeric plate , including wood or composite materials . it is important to emphasize the possible advantages of virtual or foldable decks , since portability of a liquid handling android constitutes a main advantage for service and support operations , making the shipment of the android more effective cost - wise . in addition , a foldable or virtual deck allows saving space when the android is not in use . the deck could contain a plurality of locations providing specific information , either to the user either to the system itself . for example , labels , warnings , instructions , precautions , and disclaimers addressed to the user , but also localization marks , barcodes , coded symbols , tags , fiducial spots , to improve the space localization of the pipette and the consumables by means of the cameras . a plurality of types of consumables , for example the microplates indicated as 107 , can be positioned onto the deck , either in a free format configuration , either in fixed or almost fixed format configuration . a fixed format configuration implies to precisely localize the consumable in a given position , without leaving an arbitrary choice for its orientation , while an almost fixed format configuration indicates an approximate region for the consumable , but leaving the option of rotations and displacements in proximity of the nominal position for the same . fixed format configurations may profit from slots , rails or similar solutions . in all configurations , the presence of serigraphic or printed graphics can facilitate the user job of positioning a plate , but also simplifying the function of consumable localization by the cameras and providing a sense of order to the user perception , making the repetition of the same protocol an easier task . optionally , the printed graphics and information could be performed in different colours , making the camera more selective to identify a part of the information hereby present . the arm , in this case defined as the structure between element 110 and element 113 , comprises a plurality of actuators or solutions with a similar functionality ( for example , a cable driven system where the motors are actually localized outside the arm , or a pneumatic system using cylinders as actuators ). in the present embodiment , actuators are chosen from the category of servo motors integrating gear reduction and angular feedback , allowing setting the actuator to a given angle between its body and the output axis . in a single unit , for example unit 110 , the provision of power and serial communication link ( for example based on the rs232 , rs485 or usb standards ) allows to input and output different information : examples of input are the desired position , the velocity profile for a movement , the maximum torque , the angular acceptance window ; examples of output are the current position , the current velocity , the unit temperature , the unit status , and possible faults . the motion of the arm occurs mainly in the horizontal plane , being typical biochemical operations performed on a planar and horizontal bench with consumables which have a marginally different height . however , the insertion of tips and the aspiration and dispensing of liquids , for example , also require vertical movements . in this specific embodiment , the arm operates mostly in the horizontal plane and it has a more limited excursion in the vertical plane . one way to achieve the required displacement , for example , would be relying on two angular actuators setting the position in the horizontal plane and a vertical linear actuator . in alternative , the weight and complexity of the linear actuator could suggest its replacement by two angular movements , for example the angular actuators 112 and 113 , allowing moving the pipette up and down by conserving its orientation in space through simultaneous movement . this feature can be important in consideration of the fact that the pipette verticality constitutes an important requirement for better volumetric performances of pipettes . for other reasons , it could be preferable to increase the number of angular actuators for a movement in the horizontal plane . for example , in some embodiments it could be desirable to define the orientation of the vertical pipette with respect to azimuthal rotations : this automatically implies at least three actuators for horizontal movements . the presence of obstacles or fixed structure could also require a larger number of actuators , for example four as depicted in fig1 . the choice of the arm configuration could follow good engineering practice and common sense , in view of the application and of the angular actuators performances . the hand design could exploit concepts and components similar to those applied to the arm . in the depicted embodiment , the hand starts from actuator 114 , which is actually the actuator taking care of the grabbing of the pipette . the grabber , not shown for clarity , can be a simple claw mechanism capable of exercising a pressure on the two sides of the pipette . it could also be a single claw mechanism , where the moving claw is opposite to a fixed claw which is conformal to the pipette . claws can have , in general , a conformal shape , a planar shape , or a limited number of contact points with the pipette . different design have different advantages : depending on the embodiment , the liquid handling android could be designed to deal with a single type of pipette , or with a multiplicity of models . it is obvious to those skilled in the art that claws have to be conceived accordingly , and their conception could be different for different pipettes . the hand may further comprise a camera 123 , to be oriented and moved in different directions , independently or dependently together with the pipette , with the purpose of identifying the consumable and its position in space but also the position of the tip 120 or the pipette 119 once it has been grabbed from the body slot 121 . it is important to realize that it is challenging to image , with a fixed camera , a typical deck surface characteristic of a biological or chemical test without going too far away from the deck . therefore , the suggested embodiment indicates a solution for the problem by imaging the deck area by a series of pictures individually covering a part of the useful surface . the image could be recomposed in a mosaic by suitable software , allowing having a synoptic view of the deck space and the consumable thereby contained . the composite imaging could also allow — by tilting or translation of the camera or of the hand — to have multiple images of the same deck or part of it . this feature could be easily exploited with the purpose of obtaining stereoscopic information in order to reconstruct at least part of the three - dimensional information . this feature is particularly relevant in order to extract information on the height of the consumable , possibly required for the correct setting of the pipette aspirating and dispensing position . three - dimensional information could also be achieved by means of using the focus information from the camera , provided that the camera has an adjustable focus and the optical configuration has a limited depth of focus . this method , would allow extracting depth information by simple scan of the object itself , and analysis of the spatial contrast of the image . a colour camera could also provide additional information , for example allowing identifying consumables and pipettes or other accessories based on the colour space distribution . the hand may include a thumb actuator 115 , whose purpose is to actuate the thumb 116 with functionality similar to the human thumb in the manipulation of a pipette . the thumb movement could be a simple partial rotation around the axis , but it is important to notice that improving the precision of the thumb action , for example in its speed , position , and pressure sensitivity with respect to a human thumb , could introduce various improvements in the pipette manipulation : for example , improved mixing of liquids by rapid aspiration / dispensing sequences through the excursion of knob 117 , improvements in the precision of dispensing by a reproducible position displacement or velocity profile , and an improved detection of the pipette stop by pressure feedback mechanisms . ultimately , the thumb action could also depend on the liquid properties — making the pipette working in optimal conditions with viscous liquids or heterogeneous samples . as another example , a fast and reproducible thumb action could improve the performances and the reliability for on - the - fly dispensing of liquids , defined as dispensing of liquids without physical contact with the recipient - contained liquid . this possibility would enable performances that are not possible to be achieved by manual pipetting operations , with significant savings in time and in the use of tips . a combination of a multiplicity of dispensing and aspirating methods , combined with the possibility of individually calibrate them for arbitrary liquids ( as described in a following section ) supports the evidence that a liquid handling android can outperform easily a manual operator , both in capacity and quality . a second embodiment of a liquid handling android is described in fig6 . a plastic enclose 601 constitutes and contains the main body , which is designed as a vertical structure mounted onto a baseplate 602 . the baseplate 602 has the purpose of providing stability to the system , and to make the system independent from possible vibrations and oscillations of the supporting bench — whether induced by the android itself or by external agents . the body 601 also include a rotating actuator 603 for the execution of the volume setting procedure . the rotating actuator is assisted by a camera 604 that , by means of the internal illuminator 605 , is capable if imaging the digital counter positioned onto the pipettes 606 . in this embodiment , the body 601 contains electronics and mechanics : in fact , the vertical movement of the arm is achieved by a linear actuator ( not visible in the picture ) that raises vertically the shoulder 607 , allowing for the required vertical excursion of the arm . as a consequence of this , the arm functionality is limited to the displacement of the hand 608 in the horizontal plane , being the vertical movements achieved inside the body 601 . differently from fig1 , the arm therefore contains only three servomotors 609 that allow for complete coverage of the intended area . details about the hand embodiment are shown in fig7 . two servomotors 701 and 702 assist the hand in manipulating the pipette , including grabbing , ejecting the tip , and actuating the pipette knob 705 for aspiration and dispensing of liquids . servomotor 701 has the double function of applying the required pressure on the pipette knob 705 , including the monitoring of the pressure feedback and the monitoring of the knob position in order to determine the pipette stop . the double functionality is achieved by means of cams , where cam 704 is always moving together with the servomotor 701 axis , while the cam 712 is actuated by the cam 704 only within a limited angular range . the pressure of cam 704 onto cam 712 actuates the button 706 on the pipette , inducing the ejection of tip 709 from the pipette . another cam is actuated by servomotor 702 : cam 703 actuates a lever ( not shown ) that slides on wedge 707 , which in its turn pushes the clamp 708 against the pipette body and results in the pipette grabbing . a symmetric mechanism is present on the other side of the pipette , resulting in a symmetric clamping force aligning the axis of the pipette with the axis of the hand . importantly , the hand hosts a camera 711 and an associated light source 710 . the purpose of the light is to apply uniform and constant illumination in the field of view of camera 711 , field of view comprising the bird flight view of the deck , the imaging of the tip 709 and in this case also of the pipette end 713 . having these elements within the field of view , allows measuring the relative position of these objects within the camera image . in fact , the correction of the optical distortion of the lens allows determining the radial line — passing through the objective of camera 711 — along which an object within the field of view lies . therefore , its transversal position can be reconstructed by estimating its vertical location . the vertical location of an element , for example the tip end , can be estimated in different ways : by means of the lens focus , by contact of the same object against a reference of known vertical position ( sensed through the pressure feedback of the vertical motion ), by multiple displaced images of an object which is not connected to the hand , by stereoscopic imaging of two cameras are mounted on the hand , by measurement of the apparent size of a 2 - dimensional barcode of known dimensions , and other methods . a possible embodiment describing methods and devices for the definition of the pre - set volume in an adjustable pipette is described in fig2 . in the picture , a camera 203 is located inside the body 201 , body already described in fig1 . the camera is positioned in such a way to be able to image the pipette display 215 ( not directly visible in the picture being covered by the pipette body but indicated for example in location 313 of fig3 ) indicating the dispensing / aspirating volume of pipette 204 . obviously , the arm which is partially visible ( actuators 213 and 214 ) has been suitably designed in order to allow this position to be reached . the camera could either image the display from the front , or from a certain angle in whatever direction and plane ( for example , from the top or from the bottom , from the left or from the right ). the camera could be assisted by artificial illumination , either from the environment or from sources contained in the liquid handling android , either from natural sources . it is useful to combine the display monitoring with the capability of adjusting the pipette volume setting . this is accomplished by the actuator 206 connected to the knob twister 207 . the actuator can be set either by its angular position , either by its angular velocity . the knob twister is an element , preferably of elastic material , which has been designed in order to be able , by simple pressure of the knob against the twister , of applying a torque on the knob therefore allowing — as done for the majority of pipette types — to perform the required pipette adjustment . in some embodiments , the twister could be a rubber based cylinder with a concave ( truncated ) cone carved into its body : the cone shape would allow to conformally adjusting to different sizes of pipette knobs . a possible embodiment describing apparatus and methods for the action of tip ejection is shown in fig3 . obviously , tip ejection in a liquid handling android is complemented by tip insertion onto the pipette . however , in most of the present pipettes the tip insertion is simply performed by applying a certain pressure when the pipette body has been inserted into the tip . clearly , this operation is feasible in an embodiment as described in fig1 . concerning the tip ejection , multiple solutions could be exploited , including the direct action of the ejection button by means of a dedicated actuator most probably located into the hand of the liquid android . however , there is an economical solution which doesn &# 39 ; t require an additional actuator , as shown in fig3 for the liquid handling android embodiment already described in fig1 . the arm allows localizing the pipette 303 in a configuration where the ejection button 305 of the same pipette is facing a fixed structure 306 , for example fixed with respect to the body structure 301 . the actuation of the ejection button is achieved by a force generated by the arm itself , for example by the action of the actuators 309 and 310 in order to have the fixed structure 306 and the ejection button 305 being pushed one against the other . this solution allows saving at least one actuator and a certain complexity in the hand , resulting in a lighter and more reliable solution . an appropriate choice of the shape of the structure 306 allows also ejecting the tip in different spatial position , something which is desirable to avoid the accumulation of tips into a limited area of the waste tray 103 shown in fig1 . a possible embodiment of methods and devices achieving volumetric monitoring and traceability of pipetting operations is shown in fig4 . the four images correspond to four different snapshots taken by a camera , which in the liquid handling android previously described could either be camera 123 or camera 102 of fig1 . for simplicity of description , the image is taken from a position which is orthogonal to the pipette axis : however , this is not strictly required and most angles of view are possible . the image can visualize in part or in full the pipette body 402 and the tip 401 . as it is visible in the leftmost image , a reference image of an empty pipette constitutes the reference and it could also be stored — temporarily or permanently . it is understood that the image could be taken in a reference position of the arm , so providing a uniform and constant background information and illumination . in the second picture from the left of fig4 , it is depicted a tip which has been loaded by a given amount of liquid , according to the volumetric settings of the adjustable pipette . it is obvious to those skilled in the art that every set volume corresponds , for a given tip , to a given location of liquid meniscus 403 . in this respect , therefore , the meniscus location constitutes an indicator that the pipette has aspirated correctly the desired amount of liquid . conversely , the reference image constitutes the logical reference after a dispensing operation , where the presence of droplets or liquid left - overs can also be detected in a similar way . in the third picture from the left in fig4 , it is shown a pathological case where the aspiration is not occurred correctly . visibly , a bubble of air 405 has been introduced in the pipette , modifying the actual liquid volume contained in the pipette with respect to the desired volume . according to the origin of the bubble , the meniscus 404 could be at the correct position ( defined according to the considerations done for the second picture from the left of the same figure ), therefore indicating that the actual liquid volume in the tip is lower than expected . the liquid meniscus could also be at a higher level , indicating for example that the bubble has been formed after aspiration , or could even be lower than expected — suggesting a serious problem in the liquid collection . a simple and practical case occurring in laboratory practice is shown in the rightmost picture of fig4 : a lack of liquid in the container where the pipette has aspirated the liquid , or the incorrect position of the tip with respect to the liquid level , has resulted in a partial aspiration of the liquid at the advantage of air contained in the pipette . the meniscus 405 is most probably in the correct position ; however a second liquid - air interface is visible in location 407 . all these undesirable behaviours can be made available to the user , significantly improving the interpretation of the data generated by the assay . in all cases , the image contains significant information that would be lost in manual operations . this useful information could either be processed online , in order to try recovering the process , either simply stored offline for operator monitoring and quality control purposes . overall , a similar imaging configuration could be used for controlling the position of a tip in a consumable with respect to the liquid level . the imaging of the consumable , and the identification of the liquid level , could allow determining the vertical distance between the liquid and the tip , allowing precise sipping or dispensing of liquids . similarly , the same procedure could be applied to aspirate liquid in particular vertical location of the liquid , for example in the case of separated blood and aspiration of buffy coat at the interface between plasma / serum and erythrocytes . a possible embodiment describing methods and apparatus for achieving vision assisted positioning of a tip is shown in fig5 . the image corresponds to the image taken by a camera which is preferably connected to the pipette hand , for example camera 123 described in fig1 . if the camera is connected to the pipette hand , grabbing the pipette 119 connected to tip 120 in fig1 will result in a reproducible and constant position of the pipette tip 504 visible in fig5 . therefore , this information constitutes already an important control on the proper grabbing of the pipette from the hand . it is understood that different pipettes and different tips could result in different images and shapes , so the tip imaging also represents a possible method for making sure that no misidentification has occurred . additionally , the image may contain — as in the case of fig5 — additional objects within the field of view . it is well known in the art that any object could be either in focus , either out of focus , accordingly to the type of optics and sensor utilized , and obviously their distance from the camera . the arm capability is such that it is possible to operate the arm at a desired height , which of course means that the distance between the consumable and the tip will be set to a desired value . in this conditions , it is possible to identify the lateral alignment of tip 504 with respect to the desired well position 507 according to the following method : the axis 504 of the tip 503 , when prolonged , will identify the trajectory that the tip will perform for a vertical movement ( in the example that the tip is vertical , as it should typically be ). however , a given and typical distance of the tip with respect to the consumable will define a single point in the image that the tip will intersect when localized at the same height of the identified well . therefore , the relative horizontal alignment of the tip can be achieved by imaging the same tip within the field of view , and applying an offset in the imaging plane : this point should be directly positioned onto the desired destination , by applying lateral movements of the arm without changing the distance of the tip from the consumable . it should be remarked that this method works also in presence of optical distortions , that can be corrected either in full by vision analysis method either by empirical alignment . in another implementation , as visible for example in fig7 , the camera can image the tip while the tip is approaching the liquid surface . with respect to an image where the tip is far away from the liquid , an image where the tip is in contact with the liquid will change the image of the tip , and therefore such change can be used to identify the position where the tip touches the liquid surface , for example with the purpose of aspirating or dispensing nearby the liquid surface . the difference in the images can be enhanced by suitable illumination of the tip or of the liquid : as soon as they come in contact , the refraction index of the tip polymer and the refraction index of a liquid are similar , and therefore light will channel through the other medium under the guidance of internal reflection along the materials surface . the change in the illumination configuration can be easily identified and lead to the detection of the tip - liquid contact . illumination conditions particularly suited to the internal reflection exploitation can be achieved by means of light emitting diodes or lasers , or under the guidance of light guides , like for example optical fibres . a possible embodiment of a deck configuration is shown in fig8 . differently from the deck described in fig1 , the consumables are organized in a geometrical manner by means of holders called blocks , defined as reusable or non - reusable supports capable of holding one or a plurality of consumables . a feature of the blocks is the possibility of assembling them into a larger structure called mosaic , which is a planar composition of blocks organized according to some pre - defined rules but with a certain pre - defined flexibility . in fig8 , different types of blocks are assembled together : for example , block 801 is intended for the collection of used tips , bock 802 is designed to contain and support different types of microtubes , block 803 is intended to hold and support tip racks , block 804 serves the support of larger tubes like for example 15 ml , 50 ml and blood tubes , and block 805 contains a microplate . these blocks are not exhaustively covering all possibilities . for example , a block could be designed to host simultaneously pre - loaded reagents , specific consumables like tips , barcodes for processing information , tubes and empty consumables for allowing the users providing their own samples . in this last configuration , it is possible to conceive a domino block as a single unit that doesn &# 39 ; t require external blocks for processing , making therefore the domino deck a collection of independent experiments that do not depend from each other . importantly , domino blocks can be complemented by information by means of nfc , rfids , linear barcodes , optical recognition marks and two - dimensional barcodes as indicated in 806 . the purpose of providing additional information reliefs the system in active and contact - less identification of the blocks , for example by means of the camera 711 described in fig7 . other ways of extracting the domino block information is by means of electrical contacts positioned on their sides and coming into contact with neighbouring blocks , and propagated to the other blocks by means of an electrical network . one important feature of a domino deck consists in the capability of adapting its configuration to the user needs , while simultaneously being able to organize and rule the assembly of the blocks . in fact , the domino block could present keys on the sides , for example mechanical keys or magnetic keys , preventing the user from assembling the domino block incorrectly , and also validating the choice of a configuration by some forces keeping the assembly all together . one embodiment for a key is a mechanical configuration , similar to those implemented in lego toys for the purpose of education and play . another mechanism consists in specific magnetic configuration : for example , along a side designed to be oriented in direction “ down ” the side could host a plurality of magnets presenting a suitable magnetic configuration . poles in the configuration sns ( south - north - south ) could be matched to sides presenting nsn ( north - south - north ) as a consequence of an attraction force , while sides nsn will be pushed away from a side nsn ( similarly to the repulsion force of a sns side when pushed against a sns side ). the advantage of a magnetic configuration consists in an attractive force validating an allowed configuration , while a repulsive force will prevent assembling blocks with the wrong orientation . these magnetic forces could also improve the overall organization of the domino deck by means of connecting to an external reference structure . for example , in fig8 the block 807 is magnetically attached to the base below the body of the android by means of a sns magnetic configuration facing a nsn magnetic configuration generated by magnets embedded on side 809 . similarly , block 808 is magnetically connected to magnets position on side 810 of the android base through an sns magnetic configuration facing a nsn magnetic configuration . in this example , what prevent to rotate by 90 degrees the block is the different pitch between magnets , shorter on side 810 with respect to side 809 . for the same reason , the blocks in the domino deck cannot be rotated by 180 degrees or by 90 degrees . one important advantage of a domino deck consists in an optimal space occupation of the laboratory bench , being external to the android body . in fact , the space occupied by the system is limited to the space required by a given experiment , contrarily to the configuration of today liquid handlers that occupy bench space irrespectively of the complexity of the experiment involved . additionally , it allows minimizing the occupied bench space when the system is not used , for example by storing the domino blocks elsewhere or by assembling them in a vertical pile occupying the footprint of a single domino block . in general , users can exploit different domino blocks according to their typical experiment , by varying the amount of blocks of the various types which are required and without using the blocks which are unnecessary . while multiple procedures and methods for positioning are known to those skilled in the art , including the use of precision mechanics and encoders and decoders of x - y - z cartesian robots , we describe a method which is particularly suited for the identification and localization of consumables by means of a simple camera mounted on the moving arm . the camera and arm geometry here described is the one shown in fig6 , the arm 609 holding a pipette 608 by means of the grabber 708 shown in fig7 together with camera 711 and related illumination 710 . fig9 represent a possible image taken by camera 711 while moving above a certain block , to be accessed precisely for the purpose of pipetting in one given position ( for example well 910 ). it should be noted it is critical to extract the relative position of the pipette axis in three dimensions with respect to the desired pipetting location . known the pipette tip length ( for example by the pipette model or by other techniques including the sensing of the pipette tip contact , stereoscopic imaging , external measurement by means of camera 604 of fig6 , and other methods ), and given the fact the pipette tip could be visible within the field of view of the camera ( as possible in fig7 for pipette 709 by exploiting a suitable objective for camera 711 ), it is evident that the lateral position of the pipette tip end with respect to the camera axis can be computed in the space of the image sensor coordinates ( pixels ) and converted in real space lateral displacement once the conversion scale is known for the plane where the pipette tip end resides . the conversion scale can be achieved in multiple ways , including the use of a two - dimensional barcode of known dimensions in the same plane . however , fig9 shows that knowing the relative position of the pipette tip end with respect to the camera is a partial solution to the problem addressing the positioning of the pipette tip end into a well 910 , since it is still required to move the camera axis ( shown by the hatched cross 901 ) at a given offset ( in the real space ) with respect to the consumable 902 . the following method shows a procedure which has the advantage of being rapid and robust , being capable of compensating any misalignments and locally adjusted for each individual block or small area of the deck . in fact , block 911 is equipped with different features . one feature is the presence of mirrors 903 , 904 , 905 , 906 positioned on planes which are at 45 degrees with respect to the horizontal plane , and reflecting in the upward direction the image from the side of the microplate . these mirrors allow the optical inspection of any user - labelled barcode put on the vertical sides of the microplates , that can be measured by the camera 711 easily irrespectively of the sides where the barcode is applied , and potentially detecting any microplate rotation if the user barcode should be in a given side of the microplate . the same barcode identification capability can be exploited to detect other barcodes implemented into the block 911 in positions 909 and 908 for example . it should be emphasized that the choice of two barcodes could be reduced to a single barcode and could be extended to a plurality of those , with the purpose of increasing the system robustness or the amount of information to be read by the camera . the two dimensional barcodes mounted in block 911 are positioned at about the same height of the wells , or at a known offset in the vertical plane . the reading of a barcode , for example of a qr barcode , also provides to the user information about its apparent size , which is the size measured by the camera in its space ( typically , measured in pixels along the directions of the dimensions of the sensor ). having barcodes of known dimensions , or of dimensions which are reported into the content of the barcode itself , allows therefore to define the spatial conversion scale to convert any distance measured by the camera in the same plane into real dimensions . alternatively , if the barcode is of unknown dimensions , two barcodes at a known distance can serve the same purpose , for example by knowing the distance between barcode 908 and barcode 909 . indeed , for the case of camera with unknown pixel shape the information about the barcode angle has to be used in order to extract the suitable conversion scale ( different in the two directions of the image sensor ). in summary , measuring the dimensions and the angle of a single two - dimensional barcode allows for measuring distances in the same plane of the barcode , or in its proximity . however , for a given camera and objective the conversion scale changes with the distance according to simple projective rules , once the camera images are corrected for the objective distortions . so , a vertical scan performed by moving vertically the camera at known steps ( for example , knowing the gear factor and the steps of a motor moving the arm vertically , allows to construct a curve that automatically provides the user , by interpolation and extrapolation , the vertical distance for a given camera and objective from the barcode itself . ultimately , the same curve can be used in a reverse manner to extract the actual distance of the camera from the barcode , and knowing the offset of the pipette tip end with respect to the camera : this inverse method allows solving the problem of vertical positioning of the pipette end tip with respect to well 910 . similarly , the lateral offset of the camera axis 910 with respect to well 910 can be computed by knowing the lateral offset of well 910 with respect to a barcode 909 in the reference frame described by arrows 912 and 907 . this offset is specific to each module , and can be stored into a suitable way externally or internally to the module ( for example , by means of a database , inside the barcode data , or by an rfid or nfc tag ). to achieve the target of relative positioning of the arm , it should be noted that the camera axis 901 is localized in the reference frame 912 and 907 by the measurement of the barcode angle , its position in the sensor image and the previously described spatial conversion scale : the transformation between the camera reference frame and the real space reference frame of the block become uniquely identified by a single image . so , putting all elements together , the present method allows precise relative positioning of a pipette with respect to a location in a given consumable by means of a camera mounted on a robotic arm , using the information provided by a barcode . in fact , the present method can be used also for precisely identify the parameters transforming the angles of the servomotors 609 of fig6 into relative coordinates within one block . this approach has the advantage of precisely refine the mechanical precision in presence of the arm twisting , bending , imperfections in the angular determination , inaccurate arm sizes and dimensions , assembly inaccuracies and in general improving the reproducibility . in summary , the non - linear , non - invertible transformation of the servomotors angles into the camera position in the real space depends on a large number of external parameters , but is a known analytical function following basic trigonometric rules . however , many of these parameters are more accurate when computed locally , for example the bending of the arm could vary as a function of the arm configuration ( its extension , for example ). the method here disclosed is based on multiple images of block 911 — similar to the image of fig9 — where the images are displaced by a known , local angular amount for any of the motors , allows creating a dataset of images where the barcode position and angle is measured within the camera image . using the arguments explained before for a single image , the distances between the theoretical positions of the camera in the barcode reference frame 912 and 907 and the actual distances can be minimized by means of a least squares minimization algorithm , and therefore an optimal local transformation can be created and used afterwards . this procedure can be repeated rapidly over time , for example triggered by a large discrepancy between theoretical positions and actual positions during the arm operations , in order to maintain the system highly reproducible . in fig1 , an example of the residuals that can be obtained by changing individually the angular position of the three servomotors 609 shown in fig6 , for a number of angular settings ( each of the intersecting lines corresponding to the modification of the angle of one individual motor , as indicated in the plot labels ). the arrows in the plot indicate the residuals , defined as the deviation of the expected position vs . the actual position measured by the camera , after having applied the previously mentioned minimization procedure . the size of the arrows ( magnified by a factor 5 × in order to make them visible in the plot ) indicates the error in positioning of the system . the method here described allowed improving the spatial precision of the system by a factor 6 ×, taking average residuals from 6 mm ( mainly given by the precision of the mechanical system and of the electronics ) to less than 1 mm . a problem specific to liquid handling instrumentation is the need of identify , localize , count and dispose the liquid handling consumable called tip . there many different types of tips — and typical liquid handling operations imply the disposal of the tip after each liquid dispensing step , to avoid further contamination . the consequence is a complex logistics even for relatively simple protocols , both in manual operations and liquid handling performed by automated systems . in particular , pipette tips in some disciplines have also strict requirements in terms of sterilization and contamination before operations actually have place : the consequence is that a typical laboratory has a very complex tip management logistics , induced by multiple tip types , compatibility of each tips for each equipment and manufacturer , and of the formats and packaging associated to those . essentially , all instrument manufacturers supply users with their own tip racks , tip rack being the name for a structure organizing tips in a regular array , and try to offer the widest choice possible in order to allow any operation on any instrument . consequently , tips supply becomes an expensive activity both for users and instrument suppliers . hereby , we describe a novel solution allowing our androids to use any tip which is already being used in the laboratory . the solution is totally independent from the tip rack , e . g . the holder containing the tips . the solution allows also to identify uniquely the tips , and to know which tips are usable in a rack without the requirement ( demanded by most instruments ) to start operations with unused and new tip racks . in this way , evident economy can be achieved by the customer , simultaneously obtaining the maximum flexibility in using high quality consumables on the android . the solution consists in identifying and localizing tips by means of top - view vision , for example the one achieved by means of camera 711 in picture 7 . any tip rack can be positioned in a domino block like the one shown in fig1 , the domino block essentially being a simple box ( possibly with a surface with an anti - slip pad to avoid undesired movement over time of the tip rack itself ) capable of hosting the vast majority of tip racks commercially available . it is very common to purchase tip racks that organize the tip consumables in the same geometrical configuration of microplate wells , e . g . a rectangular array of 12 × 8 tips which are spaced apart by 9 mm . assuming this configuration , in order to be able to use tips effectively we need to deal with various aspects : the identification of the type of tips , the identification of the available tips , the determination of the height of the tip upper part that will come in contact with the pipette end . even if these operations could be performed by direct image processing , e . g . vision - based algorithms identifying shapes and structures , it would be hard to be robust enough to be able to deal with hundreds of different configurations and designs which are not known a - priori . our vision - based solution consists in inserting into the tip racks two buttons 1101 and 1102 . the buttons could be either inserted by the user before executing an experiment , but also before autoclaving the tips for further reuse , or at manufacturing . the two buttons could be made in different ways : as a simple cork to be inserted into a tip of the corresponding type , or as a passive stub similar to the upper part of a tip and having about the same external diameter . buttons would require a barcode or similar optical mark at the top , the barcode being an easy and robust solution for identification and localization by the top - vision camera mounted on the arm . the advantage in using two - dimensional barcode consist in the fact that they will automatically provide the precise vertical position of the tip for grabbing , and also the correct transversal scale for identifying the conversion scale in the image allowing to reconstruct spatial dimensions . spatial coordinates are needed both for guiding the movement of the arm in order to grab a tip , but also to compute and determine the number of available tips , and their localization . in fact , barcodes 1101 and 1102 would be used to define the region of the tip rack where tips are present . in the example from fig1 , all the 34 tips localized in the matrix defined by the two buttons as corners would become a region from which the arm will pick the tips , region highlighted in the picture by means of the dashed rectangular perimeter 1103 . it is evident by anybody skilled in the art that the suitable choice of the corners would allow choosing the region of the tip rack to use , and allow counting ( by means of the known pitch among tips ) the number of tips available . similarly , the content of the barcode would provide to the system the information on the type of tips being hosted in the specific rack . the method here described by means of two barcodes , can be easily extended to a plurality of barcodes and different methods for indicating the usable sector of the rack for tips extraction . this method therefore provides the way of localize , identify and count tips in a substantially generic tip rack , and the same principle could be used for the extraction of partial information — for example in combination with tip recognition methods to discover possible holes in the tips formatting ( as an hypothesis , one tip being absent in location 1104 ). it should be noted that the same method can be applied to different types of consumables that imply picking operations : for example , needles for the purpose of liquid handling could be considered under the same methodology , with equivalent advantages . an important element of the liquid handling android is constituted by the software interface , a generic name including the package communicating with the camera , actuators and electronics , controlling and synchronizing their operations , processing the information to be sent and collected , but in particular interacting with the user and external sources of information ( websites and servers , for example ). the interaction with the user consists both on the system programmability and the provision of feedback related to the liquid handling process , including its execution performances , faults , checkpoints . in one possible embodiment , the cameras and the actuators of the liquid handling android are controlled by means of usb , and a usb hub is localized inside the body . in this embodiment , a single usb cable can connect the personal computer or the tablet constituting the user interface to the liquid handling android itself . in other embodiments , a wi - fi connection could serve for the purpose avoiding the necessity of a physical link . the controlling software could therefore exploit usb drivers and software development kits provided with the individual components with the purpose of minimizing the development , and similarly integrate existing packages for the vision processing and for the inverse transformation determining a set of actuators angles for a given position , in angle and space , of the pipette . an important aspect of software is constituted by the user interface . the availability of cameras capable of capturing real images of the process suggests using an approach based on virtual reality , where the user is provided with information — on the screen of the controlling system — which results partially from real images and partially from synthetic information . in this way , the adherence of the original protocol can be made in a more user - friendly way , improving the performances of the operator and reducing possible faults to minimum . the software interface could also interact with the user during the execution of liquid handling steps . for example , a protocol could require specific liquid handling steps — or operations like spectrophotometry , phase separation , microscope inspection or similar — which cannot be executed from the android itself . therefore , the software interface will trigger the user intervention ( or in alternative simply wait for it ) for example by means of visual indicators , hand waiving , acoustic signals , emails , sms or phone calls to the user . the purpose of the software is not limited to the execution of protocols , but it could also be extended to other operations having , for example , the purpose of improving the hardware performances . for example , it is well known in the art that accurate pipette performances require frequent calibration of the same , being the performances related to environmental parameters and also to their use . a liquid handling android could be controlled by software in such a way to execute pipette calibration procedures for example repeating a sufficient number of dispensing steps into a consumable , and monitoring ( by weight , colorimetry , fluorescence or similar techniques ) a physical parameter representative of the dispensed volume . it should be noted that — in a liquid handling android — there is no strict need of physically adjust the pipette calibration scale , since the software could automatically define the calibration table , and therefore the knowledge of the actual volume to be set in order to achieve a desired volume . having now described a few embodiments of the invention , it should be apparent to those skilled in the art that the foregoing is merely illustrative and not limiting , having been presented by way of example only . numerous modifications and other embodiments are within the scope of ordinary skill in the art and are contemplated as falling within the scope of the invention as defined by the appended claims and equivalents thereto . the contents of any references cited throughout this application are hereby incorporated by reference . the appropriate components , processes , and methods of those documents may be selected for the present invention and embodiments thereof .	1
this invention simplifies what has been attempted before in a very elegant aerodynamic execution of a device which not only distributes the fibers uniformly in the cross machine direction , but also allows them to be formed into a web . it is well known and published in the art what the key aerodynamic parameters for conveying solid particles in an air stream . the difficulty has been in developing a device that can maintain these conditions and distribute fibers onto a forming zone . a forming zone on most air laid machines is a foraminous screen supported over a vacuum table to consolidate the individual fibers into a web . other forming zones are rotary vacuum drums or condensers into which the air is blown into and the fibers are matted into a web on its surface later to be transferred to another process operation . other forming zones are composed by air conveying the individual cellulose fibers into a curtain of molten polymeric fibers as they are extruded from the die and later consolidated in a blended form onto a forming screen . fig6 shows a typical installation of this device , items 60 and 70 , with in association with a forming zone comprised of a forming vacuum box with a foraminous forming screen item 90 , as well as a meltblown extrusion die identified by item 80 . fibers or particles , because they are denser and consequently heavier than air , tend to follow their own trajectories due to the iso - kinetic forces exhibited in the air stream . therefore , it is imperative that air forming devices be designed to accommodate not only for the air characteristics required , but also accommodate the ability to uniformly convey and distribute particles or fibers in the cross direction , especially when a substrate or web is to be formed from the device . fibers , especially cellulose fluff fibers , need to be well defibrated into individual fibers . this process is . well understood in the industry , with several successful designs currently in the market place . companies like kamas , m & amp ; j , and famecannica have developed devices to defibrate pulp into individual fibers for many years now . the biggest use of these fibers is in absorbent cores for disposable products such as baby diapers and feminine care sanitary products . fibers from such devices can then be conveyed by air to their final fluff forming devices . in the case of forming absorbent batts in which the thickness or basis weight of the batt is large ( greater than 100 gsm ) the aerodynamic characteristics of the fluff forming devices are not as critical . the aerodynamic and design characteristics of the forming device become much more critical when the requirement is to form a substrate of less than 100 gsm and closer to the 20 gsm level . the challenge becomes on taking fibers that are being conveyed in a round duct at velocities that are typically in the 1000 to 10 , 000 fpm range and spreading these fibers to widths up to five meters wide while achieving a uniformity of the fibers or particles ranging under +/− 10 % by accepted standard test methods used in measuring this parameter . the present invention uses sound engineering principles in achieving this goal . the critical parameter of this invention is to take fibers from a circular duct and spread them to widths of approximately 1 . 5 to 3 . 2 meters or greater uniformly . fig1 shows the device which accomplishes this goal . it is a funnel like device which is fed by a round duct conveying fibers in an air stream . prior to the introduction of fibers into the air stream the spreading and forming device needs to provide air flows at the discharge which are extremely uniform in the cross direction . this is accomplished by maintaining constant or accelerating velocities through the funnel length , as the area at the discharge of the round duct is the same or slightly greater than the rectangular opening at the discharge of the funnel . this concept of maintaining constant or slightly accelerating air velocities through any cross sectional plane such that aa =& gt ; bb =& gt ; cc =& gt ; dd as shown in fig1 items 10 , 20 , 30 , and 40 of the spreading device is critical in achieving uniform cross direction air profiles at the discharge of the unit . fig4 shows the air profiles that are achieved applying these techniques to the forming device . this data was obtained from an unmodified discharge nozzle profile . it can be basically made flat when the profile control system shown in fig5 is implemented . the second key parameter is to have the fiber velocities which are equivalent to the air velocities of the conveying air stream be dissipated so that the iso - kinetic energy of the fiber is greatly reduced as it enters the spreading device . this is accomplished by the geometry of item 50 of fig2 , which shows the round duct entering the funnel at an angle , thus having the fibers hit the far wall of the spreading device . in this manner the velocity of the fibers and the momentum of the fibers are dissipated . this allows the fibers then to be re - aligned with the airflow profiles that will be developed by the geometries used in the design of the spreading device . if this step is not done , the fibers would have the tendency to stay in the center of the device creating a heavier center on the substrate formed . the angle of the circular duct can vary , as long as the fiber velocity is dissipated as they strike the back wall of the spreading and forming device . other means of conveying the fibers to the entrance of the forming device can be contemplated so that the velocities of the individual fibers align themselves with the velocities of the air stream . once the fibers are in the spreading and forming device , it is important that they have enough residence time in the device to streamline themselves to the airflows that have been developed within the device . this is accomplished by having the length of the device be at a minimum equivalent to ten times the diameter of the round feed duct for the fibers . lengths much shorter than 10 equivalent diameters will result in less efficient fiber spreading in the cross direction and worse profiles . the third key element of this invention is the ability to control the discharge of the fibers onto a foraminous forming screen or onto another fiber stream in order for the fibers to blend with these fibers forming a web . in this case the angle in which the fibers are directed onto either a forming zone , or is critical . this angle may require adjustment . item 60 in fig2 shows a device which is used at the discharge end of the spreading device to turn the fibers in the proper direction . the figure shows a nozzle with 90 ° turn . this angle is adjustable and can be adjusted to be whatever the application requires it to be . another method that can be used to adjust for the angle is to tilt the spreading and forming device to that angle which is also required for proper web forming . another advantage that this system has is the ability to have modular forming heads . thus , they can be combined individually in the cross machine direction making the formation width of the machine a non - issue . fig3 shows the advantage of this design by showing two side to side formers . there is no limitation to the number of formers that can be combined in the cross machine direction making it possible to achieve widths of five meters or more . for practical purposes the ideal width of the formers are in the range of 1 to 1 . 5 meters . even though the fiber formers are separate , the discharge portion , item 60 in the figures shown , is a continuous piece . in this manner , the fibers are air conveyed in a uniform cross direction manner to the forming zone without any separation as a result of the separate conveying funnels . furthermore , the discharge section as is shown in fig5 , item 60 , has an adjustable bottom plate , item 61 , which can be constricted in opening by adjustable screws to influence the trajectory of both the fiber and air stream . this added control system will guarantee a uniform profile of fibers into the forming zone .	3
preferred embodiments of the present invention will now be described in detail in accordance with the accompanying drawings . fig1 is a side sectional view depicting the structure of a thermal transfer printing apparatus ( to be referred to as a printing apparatus hereinafter ) as a typical embodiment of the present invention . the overall structure of the printing apparatus will be explained first . printing sheets p stacked in a paper cassette 2 are picked up and fed one by one to an apparatus main body 1 by a pickup roller 3 . a printing sheet p is clamped and conveyed by a pair of conveyance rollers 4 , so that the printing sheet p can be reciprocally moved relative to a printing unit . in the printing unit , a platen roller 5 and thermal head 6 that generates heat in accordance with information to be printed oppose each other to sandwich a printing sheet conveyance path therebetween . the thermal head 6 presses an ink sheet 8 , which is stored in an ink cassette 7 and has an ink layer applied with hot - melt or thermal sublimation ink , and an overcoat layer used to form an overcoat on the printing surface to protect the printing surface , against the printing sheet p , and selectively heats the ink sheet 8 , thus transferring a predetermined image onto the printing sheet p , and forming a protection layer that overcoats the printing sheet p . the ink sheet 8 is prepared by juxtaposing yellow ( y ), magenta ( m ), and cyan ( c ) ink layers and an overcoat ( op ) layer each having a size approximately equal to that of the printing region of the printing sheet p to cover the printing region . every time color ink for each layer is thermally transferred , the printing sheet p is returned to a print start position ( p 1 ), thus transferring the respective color inks on the printing sheet to overlap each other . in this way , the printing sheet p is reciprocally moved in correspondence with the total number of color ink and overcoat layers , and is finally guided to a pair of exhaust rollers 9 and is exhausted outside the apparatus housing , thus ending the printing operation . since the normal thermal transfer printing apparatus frame - sequentially prints three colors y , m , and c , control for accurately matching the printing leading ends of the respective colors is required . for this reason , the pair of conveyance rollers 4 must securely clamp and convey the printing sheet p without releasing it . as a result , unprintable margin portions must be required on the edge portions of the printing sheet p . in order to finally obtain a print without any extra - margins , as shown in fig2 the printing sheet p has perforations 22 formed by dotted - line pattern holes as cut - off portions that allow the user to easily manually cut off margin portions where no image can be printed since they are securely clamped by the pair of conveyance rollers 4 at the beginning of the print process . in this embodiment , an image is printed using such printing sheet p with perforations and the thermal transfer printing apparatus , and no overcoat agent is applied to the regions of the cut - off portions formed on the printing sheet p upon printing . the pair of conveyance rollers 4 include a pinch roller 42 and grip roller 41 , and the rotating shaft of a stepping motor ( not shown ) is directly coupled to the grip roller 41 via a reduction gear mechanism to freely drive the grip roller 41 in the forward / reverse direction under the rotation control of the stepping motor . since the printing sheet p is securely clamped and reciprocally conveyed by the pair of conveyance rollers 4 , it is conveyed while undergoing accurate position control by means of the rotation control of the stepping motor . if the printing pitch per line by the thermal head 6 is 85 μm , and the number of steps of the stepping motor required for conveying the printing sheet p by one line is 4 , the printing sheet p can be conveyed by one line ( i . e ., 85 μm ) by controlling rotation of the stepping motor to be four steps . furthermore , the printing apparatus 1 has a printing sheet leading end sensor 10 at a position immediately before the pair of conveyance rollers 4 when they are viewed from the pickup roller 3 . with this sensor , when a printing sheet p is fed from the paper cassette 2 or is conveyed toward the exhaust rollers 9 , the leading end ( or trailing end ) of the printing sheet p is detected , and after detection the printing sheet p is fed by the predetermined number of lines and is stopped within the range that the pair of conveyance rollers 4 can clamp it . in this embodiment , convey of the printing sheet is stopped after the stepping motor has rotated for 10 lines , i . e ., for 40 steps . this position corresponds to the aforementioned print start position ( p 1 ). such operation for stopping conveyance of the printing sheet at the print start position ( p 1 ) is made a total of four times upon transferring the y , m , and c color inks and overcoat layer . note that the distance between the printing sheet leading end sensor 10 and the position where the printing sheet p is pressed by the platen roller 5 and thermal head 6 is set at 10 mm in this embodiment in consideration of the parts layout in the apparatus . when the printing sheet p stops at the print start position ( p 1 ), it is conveyed toward the exhaust rollers 9 , the printing sheet leading end sensor 10 detects the leading end of the printing sheet again , the printing sheet is fed by the predetermined number of lines , and the thermal head is driven to generate heat in correspondence with information to be printed , thus printing predetermined images of the respective color inks and transferring the overcoat layer . on the other hand , a device such as a digital still camera , digital video camera , or the like is directly connected to the printing apparatus of this embodiment via a predetermined connection cable , and data of images captured by such device are input to the apparatus via an interface ( i / f ) 11 , and the apparatus can print an image on a printing sheet on the basis of such image data . for this purpose , the printing apparatus comprises a controller 12 that incorporates an mpu 13 for executing printing control . when the mpu 13 reads out and executes codes stored in the internal rom of the controller 12 , a predetermined image process and image print process are implemented . fig3 shows the image printing position and overcoat position together with the dimensions of a printing sheet . in fig3 hatched regions undergo only an image print process , and also correspond to perforation regions . on the other hand , cross - hatched regions undergo both an image print process and overcoating . since the image printing range shown in fig3 is around 144 mm wide in the conveyance direction , 1 , 694 lines can be printed , and the stepping motor can be rotated for 6 , 776 steps to convey the printing sheet by those lines . the printing method using the printing apparatus with the aforementioned arrangement will be explained in detail below . a conventional method will be explained first for the purpose of comparison . fig4 is a flow chart showing the conventional printing method . a printing sheet p is fed from the paper cassette 2 in step s 10 , and an initial value ( n = 1 ) is set in a control parameter variable ( n ) in step s 15 . the value of the control parameter variable ( n ) is checked in step s 20 . if n = 5 , it is determined that ink transfer and overcoat layer transfer are complete , and the flow jumps to step s 35 to exhaust the printing sheet p , then ending the processing . on the other hand , if n ≠ 5 , the flow advances to step s 25 . in step s 25 , the y , m , and c inks and overcoat agent are frame - sequentially transferred . upon completion of transfer of one of the y , m , and c inks and overcoat agent , the flow advances to step s 30 to increment the value of the control parameter variable ( n ) by “+ 1 ”. after that , the flow returns to step s 20 . as described above , according to the conventional method , the transfer print processes of the respective color inks and the overcoat layer transfer process are executed in the same processing sequence . by contrast , in the printing method according to this embodiment , as shown in the flow chart in fig5 color ink transfer processes and an overcoat agent transfer process are executed in different processing steps . note that the same step numbers in the flow chart in fig5 denote the same processes as those in the flow chart in fig4 and a detailed description thereof will be omitted . after the processes in steps s 10 and s 15 , the value of the control parameter variable ( n ) is checked in step s 20 a . if n = 4 , the flow jumps to step s 30 a ; if n ≠ 4 , the flow advances to step s 25 a . in step s 25 a , the respective color inks are transferred onto the printing sheet , and details of the process are as follows : ( 1 ) after the leading end of the printing sheet p is detected , the stepping motor 116 is rotated for 116 steps to start a print process . the print start position at that time is 12 . 465 mm from the leading end ( e ) of the printing sheet . ( 2 ) while rotating the stepping motor for four steps , the thermal head is driven to generate heat , thus printing an image for one line . this print process comes to an end after the stepping motor has rotated for a total of 6 , 776 steps ( 1 , 694 lines ). the print end position at that time is 156 . 455 mm from the leading end ( e ) of the printing sheet . ( 3 ) the stepping motor is rotated for about 10 lines ( 40 steps ) for the purpose of deceleration until conveyance of the printing sheet is stopped , thus stopping conveyance of the printing sheet . ( 4 ) the stepping motor is driven in the reverse direction from that state to convey the printing sheet p in a direction opposite to that upon printing . after the printing sheet leading end sensor 10 detects the leading end of the printing sheet again , the stepping motor is rotated for about 10 lines ( 40 steps ) for the purpose of deceleration . after that , conveyance of the printing sheet is stopped . ( 5 ) in order to print an image using another color ink , the stepping motor rotates again to convey the printing sheet p . in step s 30 , the control parameter variable ( n ) is incremented by “+ 1 ”, and the flow returns to step s 20 a . after such process is repeated three times , the print processes for three colors y , m , and c are complete , and a desired image is transferred and printed on the printing sheet p 1 . at this time , since the control parameter variable ( n ) becomes n = 4 , the flow advances to step s 30 a . in step s 30 a , the overcoat layer is transferred to protect the surface of the printed image . details of the overcoat layer transfer process will be explained below . ( 1 ) after the leading end of the printing sheet p is detected , the stepping motor 116 is rotated for 116 steps to start transfer of the overcoat agent . at this time , the coating start position is 12 . 465 mm from the leading end ( e ) of the printing sheet as that upon printing . ( 2 ) while rotating the stepping motor for four steps , the thermal head is driven to generate heat , thus transferring an overcoat agent for one line . the stepping motor is rotated for a total of 48 steps ( 12 lines ), thus ending transfer of the overcoat agent . the head position at that time is 13 . 485 mm from the leading end ( e ) of the printing sheet . ( 3 ) the stepping motor is rotated for 48 steps ( 12 lines ) without driving the thermal head . the head position at that time is 14 . 505 mm from the leading end ( e ) of the printing sheet . ( 4 ) the thermal head is driven again to generate heat to transfer an overcoat agent for one line while rotating the stepping motor for four steps , and this process proceeds over a total of 6 , 588 steps ( 1 , 647 lines ) until transfer of the overcoat agent is complete . the head position upon completion of transfer is 154 . 5 mm from the leading end ( e ) of the printing sheet . ( 5 ) the stepping motor is rotated for 48 steps ( 12 lines ) without driving the thermal head , thus conveying the printing sheet . the head position at that time is 155 . 52 mm away from the leading end ( e ) of the printing sheet . ( 6 ) the thermal head is driven again to generate heat , and the overcoat agent is transferred for one line while rotating the stepping motor for four steps . the stepping motor is rotated for a total of 48 steps ( 12 lines ), thus ending transfer of the overcoat agent . the head position at that time is 156 . 54 mm from the leading end ( e ) of the printing sheet . ( 7 ) the stepping motor is rotated for about 10 lines ( 40 steps ) for the purpose of deceleration until conveyance of the printing sheet is stopped , thus stopping conveyance of the printing sheet . in this manner , the transfer print process of the respective color inks and overcoat agent are complete . finally , the flow advances to step s 35 , and the printing sheet p is guided to the pair of exhaust rollers 9 and is discharged outside the housing , thus ending the print process . therefore , according to the aforementioned embodiment , since the overcoat agent is transferred so as not to form any overcoat layer on portions of the printing sheet where perforations as cut - off portions are present , even when the margin portions of the printing sheets are cut off along the perforations after the print process , the overcoat layer can be prevented from peeling , and a high - quality printed image can be stably preserved for a long period of time . since the overcoat layer never peels , neither fine dust nor powder dust are produced due to peeling of the overcoat layer , thus preventing environmental pollution and any causes of failures of the printing apparatus . in the above description , regions where no overcoat layer is formed have been explained as predetermined regions including the perforations as cut - off portions . for the purpose of protecting an image , the predetermined regions are preferably as small as possible , and can be set within the range in which the overcoat layer can be prevented from peeling . as described above , the present invention is characterized in that when an image is formed on a printing medium having cut - off portions that allow the user to easily cut off margin portions , a region on the printing medium where ink is applied during a print process , and a region on the printing medium where a protection agent is applied during a process for forming a protection layer by applying the protection agent are appropriately set to be different from each other , and no protection agent is applied to the cut - off portions on the printing medium . hence , upon cutting off margin portions from the printing medium along the cut - off portions , the protection agent is prevented from peeling , so that no dust or powder dust can be scattered . in the above embodiment , as shown in fig3 the overcoat agent is transferred onto the nearly entire image printing region except for perforation regions for the purpose of protection of a print . in general , portions cut off along the perforations are removed and discarded . hence , no overcoat layer need be formed on such portions which are to be discarded . this embodiment is made in consideration of such situation , and a print shown in fig6 is obtained . that is , an overcoat agent is transferred onto only a region bounded by perforations formed at the two sides of the printing sheet in the conveyance direction , thus obtaining an overcoated print . in fig6 hatched regions undergo only an image print process , and a cross - hatched region undergoes both the image print process and overcoat agent transfer process . operations for obtaining such print will be explained in detail below . a printing sheet and thermal transfer printing apparatus used in this embodiment are common to those in the aforementioned embodiment . a characteristic feature of this embodiment lies in the overcoat agent transfer process in step s 30 a shown in fig5 . this process is performed as follows . ( 1 ) the overcoat agent begins to be transferred by rotating the stepping motor 212 steps after detection of the leading end ( e ) of the printing sheet . the transfer start position at that time is 14 . 505 mm from the leading end ( e ) of the printing sheet . ( 2 ) while rotating the stepping motor for four steps , the thermal head is driven to generate heat , thus transferring an overcoat agent for one line . this process proceeds over 6 , 588 steps ( 1 , 647 lines ) of the stepping motor until transfer of the overcoat agent comes to an end . the head position at that time is 154 . 5 mm from the leading end ( e ) of the printing sheet . ( 3 ) the stepping motor is rotated for about 10 lines ( 40 steps ) for the purpose of deceleration until conveyance of the printing sheet is stopped , thus stopping conveyance of the printing sheet . according to the aforementioned embodiment , since the overcoat layer is formed on only a region slightly inside the perforations , the overcoat agent can be prevented from being wasted . in the aforementioned embodiments , the overcoat agent is transferred by only turning on / off the heat generation driving of the thermal head . in order to transfer the overcoat layer more stably , the heat amount may be controlled to gradually increase at the beginning of transfer of the overcoat agent , and to gradually decrease at the end of transfer of the overcoat agent , as shown in fig7 . in the above embodiments , heat generation driving of the thermal head is stopped to stop transfer of the overcoat agent . however , the present invention is not limited to such specific arrangement . for example , the thermal head clamps and presses the ink sheet and printing sheet in the transfer print process , and transfer of the overcoat layer may be stopped by releasing the pressing operation . in the aforementioned embodiments , in the transfer print process of the y , m , and c color inks and overcoat agent , the print position management is made by detecting the leading end of the printing sheet by the printing sheet leading end sensor and managing the number of steps of rotation driving of the stepping motor with reference to the leading end detection signal . however , the present invention is not limited to such specific arrangement . for example , the print position management may be made by managing the number of steps of rotation driving of the stepping motor throughout the print operation on the basis of the number of steps of the stepping motor and the positional relationship upon conveying the printing sheet p using the leading end detection signal of the printing sheet initially detected by the printing sheet leading end sensor when feeding the printing sheet p . note that the present invention is characterized in that no overcoat layer is formed on perforation regions formed on the printing sheet so as to easily obtain a print without any extra - margins . since the transfer print process at a desired position on the printing sheet is determined by the specifications of the thermal head and the arrangement of the conveyance means as described in the above embodiments , and can be achieved by managing them using predetermined means , modifications of the present invention can be applied to printing sheets with various sizes and perforation positions . furthermore , in the aforementioned embodiments , the thermal transfer printing apparatus has been exemplified . however , the present invention is not limited to such a specific apparatus , and a printing apparatus using other printing methods such as an ink - jet printing apparatus may be used as long as they print using printing media such as printing sheets with perforations . note that the present invention may be applied to either a system constituted by a plurality of devices ( e . g ., a host computer , an interface device , a reader , a printer , and the like ), or an apparatus consisting of a single piece of equipment ( e . g ., a copying machine , a facsimile apparatus , or the like ). the objects of the present invention are also achieved by supplying a storage medium ( or recording medium ), which stores a program code of a software program that can implement the functions of the above - mentioned embodiments to the system or apparatus , and reading out and executing the program code stored in the storage medium by a computer ( or a cpu or mpu ) of the system or apparatus . in this case , the program code itself read out from the storage medium implements the functions of the above - mentioned embodiments , and the storage medium which stores the program code constitutes the present invention . the functions of the above - mentioned embodiments may be implemented not only by executing the readout program code by the computer but also by some or all of actual processing operations executed by an os ( operating system ) running on the computer on the basis of an instruction of the program code . furthermore , the functions of the above - mentioned embodiments may be implemented by some or all of actual processing operations executed by a cpu or the like arranged in a function extension card or a function extension unit , which is inserted in or connected to the computer , after the program code read out from the storage medium is written in a memory of the extension card or unit . in the above embodiments , the perforations formed by dot - line pattern holes have been exemplified as cut - off portions that allow the user to easily cut off margin portions from a printing medium . however , the present invention is not limited to the printing medium with perforations , but can be applied to a printing medium in which the thickness of a portion to be cut off is set to be smaller than the remaining portion , and a printing medium in which cut - off portions are formed of a material that allows easy cutting . as many apparently widely different embodiments of the present invention can be made without departing from the spirit and scope thereof , it is to be understood that the invention is not limited to the specific embodiments thereof except as defined in the appended claims .	1
the present invention now will be described more fully with reference to the accompanying drawings , in which preferred embodiments of the invention are shown . this invention may , however , be embodied in many different forms and should not be construed as being limited to the embodiments set forth herein ; rather , these embodiments are provided so that this disclosure will be thorough and complete , and will fully convey the scope of the invention to those skilled in the art . like reference numerals refer to like elements throughout . it will be understood that when an element or layer is referred to as being “ on ,” “ connected to ” or “ coupled to ” another element or layer ( and variants thereof ), it can be directly on , connected or coupled to the other element or layer or intervening elements or layers may be present . in contrast , when an element is referred to as being “ directly on ,” “ directly connected to ” or “ directly coupled to ” another element or layer ( and variants thereof ), there are no intervening elements or layers present . like reference numerals refer to like elements throughout . it will be understood that , although the terms first , second , third , etc . may be used herein to describe various elements , components , regions , layers and / or sections , these elements , components , regions , layers and / or sections should not be limited by these terms . these terms are only used to distinguish one element , component , region , layer or section from another region , layer or section . thus , a first element , component , region , layer or section discussed below could be termed a second element , component , region , layer or section without departing from the teachings of the present invention . spatially relative terms , such as “ beneath ,” “ below ,” “ lower ,” “ above ,” “ upper ” and the like , may be used herein for ease of description to describe one element or feature &# 39 ; s relationship to another element ( s ) or feature ( s ) as illustrated in the figures . it will be understood that the spatially relative terms are intended to encompass different orientations of the device in use or operation in addition to the orientation depicted in the figures . for example , if the device in the figures is turned over , elements described as “ below ” or “ beneath ” other elements or features would then be oriented “ above ” the other elements or features . thus , the term “ below ” can encompass both an orientation of above and below . the device may be otherwise oriented ( rotated 90 degrees or at other orientations ) and the spatially relative descriptors used herein interpreted accordingly . the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the present invention . as used herein , the singular forms “ a ,” “ an ” and “ the ” are intended to include the plural forms as well , unless the context clearly indicates otherwise . it will be further understood that the terms “ comprising ”, “ including ”, “ having ” and variants thereof , when used in this specification , specify the presence of stated features , steps , operations , elements , and / or components , but do not preclude the presence or addition of one or more other features , steps , operations , elements , components , and / or groups thereof . in contrast , the term “ consisting of ” when used in this specification , specifies the stated features , steps , operations , elements , and / or components , and precludes additional features , steps , operations , elements and / or components . embodiments of the present invention are described herein with reference to cross - section and perspective illustrations that are schematic illustrations of idealized embodiments ( and intermediate structures ) of the present invention . as such , variations from the shapes of the illustrations as a result , for example , of manufacturing techniques and / or tolerances , are to be expected . thus , embodiments of the present invention 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 . for example , a sharp angle may be somewhat rounded due to manufacturing techniques / tolerances . unless otherwise defined , all terms ( including technical and scientific terms ) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention belongs . it will be further understood that terms , such as those defined in commonly used dictionaries , should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein . fig1 a is a plan view illustrating a 3d semiconductor memory device according to an embodiment of the inventive concept . fig1 b is a cross - sectional view taken along line i - i ′ of fig1 a . fig1 c is a magnified view of a portion a of fig1 b . referring to fig1 a and 1b , a well region 102 doped with a first conductive dopant may be disposed in a semiconductor substrate 100 ( hereinafter referred to as a substrate ). the substrate 100 may be a silicon substrate , a germanium substrate or a silicon - germanium substrate , for example a common source region 105 doped with a second conductive dopant may be formed in the well region 102 . an upper surface of the common source region 105 may be disposed on the substantially same level as that of the upper surface of the substrate 100 . a lower surface of the common source region 105 may be disposed on a level higher than that of a lower surface of the well region 102 . one of the first and second conductive dopants may be an n - type dopant , and the other may be a p - type dopant . for example , the well region 102 may be doped with a p - type dopant , and the common source region 105 may be doped with an n - type dopant . a stack - structure , including insulation patterns 110 a and gate patterns 155 l , 155 a 1 , 155 a and 155 u that are stacked alternately and repeatedly , may be disposed on the common source region 105 . a plurality of the stack - structures may be disposed on the common source region 105 . as illustrated in fig1 a , the stack - structures may be extended side by side in a first direction . the stack - structures may be spaced apart in a second direction perpendicular to the first direction . the first and second directions may be parallel with the upper surface of the substrate 100 . a vertical active pattern 130 may pass through the stack - structure . the vertical active pattern 130 may be extended into a recess region 120 that is formed in the common source region 105 under the vertical active pattern 130 . therefore , the vertical active pattern 130 may be connected to the well region 102 under the vertical active pattern 130 . as illustrated in fig1 b , the recess region 120 may vertically pass through the common source region 105 . a bottom surface of the recess region 120 may be disposed on a level lower than that of the lower surface of the common source region 105 . the vertical active pattern 130 may contact the bottom surface of the recess region 120 . accordingly , the vertical active pattern 130 may contact the well region 102 . also , the vertical active pattern 130 may contact a sidewall of the recess region 120 . as a result , the vertical active pattern 130 may directly contact the common source region 105 . according to an embodiment of the inventive concept , a portion 122 of the well region 102 just under the bottom surface of the recess region 120 may have a high dopant concentration . in other words , the first conductive dopant concentration of the portion 122 of the well region 102 may be higher than the first conductive dopant concentration of another portion of the well region 102 . according to an embodiment of the inventive concept , the vertical active pattern 130 may have a hollow pipe shape or a macaroni shape . herein , the lower end of the vertical active pattern 130 may be in a closed state . the inside of the vertical active pattern 130 may be filled with a filling dielectric pattern 132 . a gate dielectric layer 150 may be disposed between a sidewall of the vertical active pattern 130 and each of the gate patterns 155 l , 155 a 1 , 155 a and 155 u . according to an embodiment of the inventive concept , as illustrated in fig1 b , the gate dielectric layer 150 may be extended to cover an upper surface and a lower surface of each of the gate patterns 155 l , 155 a 1 , 155 a and 155 u . that is , the extended portion of the gate dielectric layer 150 may be disposed between each of the gate patterns 155 l , 155 a 1 , 155 a and 155 u and the insulation pattern 110 a adjacent to each of the gate patterns 155 l , 155 a 1 , 155 a and 155 u . the gate dielectric layer 150 will be described below in more detail with reference to fig1 c . referring to fig1 c , according to an embodiment of the inventive concept , the gate dielectric layer 150 may include a tunnel dielectric layer 141 , a charge storage layer 142 and a blocking dielectric layer 143 . the tunnel dielectric layer 141 may be adjacent to the sidewall of the vertical active pattern 130 , and the blocking dielectric layer 143 may be adjacent to each of the gate patterns 155 l , 155 a 1 , 155 a and 155 u . the charge storage layer 142 may be disposed between the tunnel dielectric layer 141 and the blocking dielectric layer 143 . according to an embodiment of the inventive concept , as illustrated in fig1 c , the entirety of the gate dielectric layer 150 ( i . e ., the tunnel dielectric layer 141 , the charge storage layer 142 and the blocking dielectric layer 143 ) may be extended to cover the upper and lower surfaces of each of the gate patterns 155 l , 155 a 1 , 155 a and 155 u . the tunnel dielectric layer 141 may include oxide and / or oxynitride . the tunnel dielectric layer 141 may be single - layered or multi - layered . the charge storage layer 142 may include a dielectric material having traps for storing electric charges , for example , the charge storage layer 142 may include nitride and / or metal - oxide . the blocking dielectric layer 143 may include a high - k dielectric layer having a dielectric constant higher than that of the tunnel dielectric layer 141 . for example , the high - k dielectric layer in the blocking dielectric layer 143 may include metal - oxide such as aluminum - oxide or hafnium - oxide . furthermore , the blocking dielectric layer 143 may further include a barrier dielectric layer . the barrier dielectric layer in the blocking dielectric layer 143 may include a dielectric material having a greater band gap than the high - k dielectric layer in the blocking dielectric layer 143 . for example , the barrier dielectric layer may include oxide . the barrier dielectric layer may be disposed between the high - k dielectric layer and the charge storage layer 142 . a lowermost gate pattern 155 l in the stack - structure may correspond to a ground selection gate . a ground selection transistor including the lowermost gate pattern 155 l may include a vertical channel region that is defined in the sidewall of the vertical active pattern 130 . as illustrated in fig1 a and 1b , the entire lower surface of the lowermost gate pattern 155 l may substantially overlap with the common source region 105 . an uppermost gate pattern 155 u in the stack - structure may correspond to a string selection gate . gate patterns 155 a 1 and 155 a between the uppermost gate pattern 155 u and the lowermost gate pattern 155 l may correspond to cell gates . a string selection transistor including the uppermost gate pattern 155 u and cell transistors including the cell gates may also include vertical channel regions that are defined in the sidewall of the vertical active pattern 130 a . the vertical channel regions of the ground selection transistor , the cell transistor and the string selection transistor configuring one cell string may be defined in the vertical active pattern 130 . according to an embodiment of the inventive concept , among gate patterns used as the cell gates in the stack - structure , a gate pattern most adjacent to the lowermost gate pattern 155 l may correspond to a dummy cell gate . for example , the gate pattern 1551 a disposed just on the lowermost gate pattern 155 l may be a dummy gate pattern . for example , the gate pattern 155 a 1 that is stacked secondly from the substrate 100 may be a dummy cell gate . naturally , one of the insulation pattern 110 a is disposed between the lowermost gate pattern 155 l and the secondly - stacked gate pattern 155 a 1 . for example , a dummy cell transistor including the secondly - stacked gate pattern 155 a 1 may have the same shape as that of a cell transistor storing data , but may not serve as the cell transistor . for example , the dummy cell transistor may perform only a turn - on / off function . thus , the secondly - stacked gate pattern 155 a 1 may be a second ground selection gate . in this case , the cell string may include a plurality of stacked ground selection transistors . a plurality of the vertical active patterns 130 may pass through each of the stack - structures . as illustrated in fig1 a , the vertical active patterns 130 passing though each of the stack - structures may be arranged in the first direction to form one column . alternatively , the vertical active patterns 130 passing though each of the stack - structures may be arranged in a zigzag shape in the first direction . the vertical active pattern 130 may include a semiconductor material . for example , the vertical active pattern 130 may include the same semiconductor material as that of the substrate 100 . the vertical active pattern 130 may have an undoped state , or may be doped with the first conductive dopant . the vertical active pattern 130 may have a poly - crystalline state or a single crystalline state . the gate patterns 155 l , 155 a 1 , 155 a and 155 u include a conductive material . for example , the gate patterns 155 l , 155 a 1 , 155 a and 155 u may include at least one of a doped semiconductor ( for example , doped silicon and others ), a metal ( for example , tungsten , aluminum , copper and others ), a transition metal ( for example , titanium , tantalum and others ) or a conductive metal nitride ( for example , a titanium nitride , a tantalum nitride and others ). the insulation patterns 110 a may include oxide . a device isolation pattern 160 a may be disposed between the stack - structures . an upper surface of the device isolation pattern 160 a and an upper surface of the stack - structure may substantially be coplanar . an interlayer dielectric 165 may be disposed on the substrate 100 . a contact plug 167 may be connected to an upper end of the vertical active pattern 130 through the interlayer dielectric 165 . a drain being doped with the second conductive dopant may be formed in the upper portion of the vertical active pattern 130 . a lower surface of the drain may be disposed on a level adjacent to an upper surface of the uppermost gate pattern 155 u . a bit line 170 may be disposed on the interlayer dielectric 165 , and may be connected to the contact plug 167 . the bit line 170 may be extended in the second direction and cross over the stack - structure . the interlayer dielectric 165 may include oxide . the contact plug 167 includes a conductive material . for example , the contact plug 167 may include tungsten . the bit line 170 also includes a conductive material . as an example , the bit line 170 may include tungsten , copper , aluminum or the like . according to the above - described 3d semiconductor memory device , the vertical active pattern 130 may be disposed in the recess region 120 passing though the common source region 105 and be connected to the well region 102 . moreover , the common source region 105 may be disposed under the lowermost gate pattern 155 l . therefore , a distance between the vertical active pattern 130 and the common source region can be minimized , and also the vertical active pattern 130 can be connected to the well region 102 . consequently , a current flowing through the vertical active pattern 130 can quickly flow to the common source region 105 . accordingly , the reduction of an amount of current in a cell transistor can be minimized . also , the vertical active pattern 130 is connected to the well region 102 , such that the erasing operation of cell transistors is very easy . as a result , the 3d semiconductor memory device can be implemented which has excellent reliability and is optimized for high integration . next , the modification examples of the 3d semiconductor memory device according to an embodiment of the inventive concept will be described below with reference to the accompanying drawings . in the modification examples , a description on the same elements as the above - described elements will be omitted for avoiding a repetitive description . fig2 a is a cross - sectional view taken along line i - i ′ of fig1 a for describing a modification example of a 3d semiconductor memory device according to an embodiment of the inventive concept . referring to fig2 a and according to the modification example , protection dielectric patterns 173 a may be disposed between the insulation patterns 110 a and the vertical active pattern 130 and between the inner sidewall of the recess region 120 and the vertical active pattern 130 . the protection dielectric pattern 173 a may include a dielectric material for protecting the vertical active pattern 130 in a fabricating process . for example , the protection dielectric pattern 173 a may include oxide . according to the modification example , a capping semiconductor pattern 175 may be disposed on the vertical active pattern 130 . the capping semiconductor pattern 175 may also be disposed on the protection dielectric pattern 173 a that is disposed between an uppermost insulation pattern 110 a and the vertical active pattern 130 . the upper end of the vertical active pattern 130 may be disposed on a level lower than an upper surface of the uppermost insulation pattern 110 a . the upper surface of the capping semiconductor pattern 175 and the upper surface of the uppermost insulation pattern 110 a may be substantially coplanar . the capping semiconductor pattern 175 may include the same semiconductor material as that of the vertical active pattern 130 . the capping semiconductor pattern 175 may be doped with the second conductive dopant . the contact plug 167 may be connected to the capping semiconductor pattern 175 . fig2 b is a cross - sectional view taken along line i - i ′ of fig1 a for describing other modification example of a 3d semiconductor memory device according to an embodiment of the inventive concept . referring to fig2 b and according to the modification example , a bottom surface of the recess region 120 may be disposed on a level higher than the lower surface of the common source region 105 . in this case , a region 122 a being counter - doped with the first conductive dopant may be disposed under the bottom surface of the recess region 120 a . the counter - doped region 122 a may contact the vertical active pattern 130 and the well region 102 . therefore , the vertical active pattern 130 may be connected to the well region 102 through the counter - doped region 122 a . fig3 a is a cross - sectional view taken along line i - i ′ of fig1 a for describing still other modification example of a 3d semiconductor memory device according to an embodiment of the inventive concept . fig3 b is a magnified view of a portion b of fig3 a . referring to fig3 a , a gate dielectric layer 150 a according to the modification example may be disposed between a vertical active pattern 130 a and each of the gate patterns 155 l , 155 a 1 , 155 a and 155 u . the gate dielectric layer 150 a may include a first sub - layer 147 and a second sub - layer 149 . the first sub - layer 147 may be substantially extended vertically and be disposed between the vertical active pattern 130 a and the insulation pattern 110 a . the second sub - layer 149 may be substantially extended horizontally and cover the lower surface and upper surface of each of the gate patterns 155 l , 155 a 1 , 155 a and 155 u . the gate dielectric layer 150 a may include the tunnel dielectric layer , the charge storage layer and the blocking dielectric layer . herein , the first sub - layer 147 may include at least a portion of the tunnel dielectric layer , and the second sub - layer 149 may include at least a portion of the blocking dielectric layer . one of the first and second sub - layers 147 and 149 may include the charge storage layer . in other words , a portion of the gate dielectric layer 150 a including the tunnel dielectric layer , the charge storage layer and the blocking dielectric layer may be extended vertically , and another portion of the gate dielectric layer 150 a may be extended horizontally . the vertical active pattern 130 a may include first and second semiconductor patterns 123 and 124 . the first semiconductor pattern 123 may be disposed between the second semiconductor pattern 124 and the first sub - layer 147 . the first semiconductor pattern 123 may contact the first sub - layer 147 . according to an embodiment of the inventive concept , the first semiconductor pattern 123 may have a macaroni shape or a pipe shape where an upper end and a lower end are opened . the first semiconductor pattern 123 may not contact the inner surface of the recess region 120 by the first sub - layer 147 . the second semiconductor pattern 124 may contact the first semiconductor pattern 123 and the inner surface of the recess region 120 . the second semiconductor pattern 124 may have a macaroni shape or a pipe shape where a lower end is closed . a filling dielectric pattern 132 may fill the inside of the second semiconductor pattern 124 . the first and second semiconductor patterns 123 and 124 may have an undoped state or be doped with a dopant ( i . e ., the first conductive dopant ) having the same type as that of the well region 102 . according to an embodiment of the inventive concept , as illustrated in fig3 b , the first sub - layer 147 of the gate dielectric layer 150 a may include a tunnel dielectric layer 141 , a charge storage layer 142 and a barrier dielectric layer 144 . in this case , the second sub - layer 149 may include a high - k dielectric material ( for example , metal - oxide such as aluminum oxide or hafnium oxide ) having a dielectric constant higher than that of the tunnel dielectric layer 141 . the barrier dielectric layer 144 may include a dielectric material having a greater band gap than that of the high - k dielectric material . for example , the barrier dielectric layer 144 may include oxide . the second sub - layer 149 and the barrier dielectric layer 144 , disposed between the charge storage layer 142 and each of the gate patterns 155 l , 155 a 1 , 155 a and 155 u , may included in the blocking dielectric layer . in other words , the first sub - layer 147 may include the tunnel dielectric layer 141 , the charge storage layer 142 and a portion ( i . e ., the barrier dielectric layer 144 ) of the blocking dielectric layer , and the second sub - layer 149 may include another portion ( i . e ., the high - k dielectric layer ) of the blocking dielectric layer . however , an embodiment of the inventive concept is not limited thereto . the first and second sub - layers of the gate dielectric layer may be combined differently . fig3 c is a magnified view of a portion b of fig3 a for describing even other modification example of a 3d semiconductor memory device according to an embodiment of the inventive concept . referring to fig3 c , a first sub - layer 147 a of a gate dielectric layer 150 b according to the modification example may include a tunnel dielectric layer 141 and a charge storage layer 142 , and a second sub - layer 149 a of the gate dielectric layer 150 b may include a barrier dielectric layer 144 and a high - k dielectric layer 146 . the high - k dielectric layer 146 may be formed of the same material as the high - k dielectric material that has been described above with reference to fig3 b . according to the modification example , the second sub - layer 149 b may correspond to a blocking dielectric layer . according to the modification example , the first sub - layer 147 a may include the tunnel dielectric layer 141 and the charge storage layer 142 , and the second sub - layer 149 a may include the blocking dielectric layer . fig3 d is a magnified view of a portion b of fig3 a for describing yet other modification example of a 3d semiconductor memory device according to an embodiment of the inventive concept . referring to fig3 d , a first sub - layer 147 b of a gate dielectric layer 150 c according to the modification example may include the tunnel dielectric layer , and a second sub - layer 149 b of the gate dielectric layer 150 c may include the charge storage layer 142 and the blocking dielectric layer 143 . according to the modification example , the tunnel dielectric layer in the gate dielectric layer 150 c may be extended vertically and be disposed between the vertical active pattern 130 a and the insulation pattern 110 a , and the charge storage layer 142 and the blocking dielectric layer 143 in the gate dielectric layer 150 c may be extended horizontally and cover the upper surface and lower surface of each of the gate patterns 155 l , 155 a 1 , 155 a and 155 u . the first and second sub - layers according to an embodiment of the inventive concept are not limited to the modification examples that have been described above with reference to fig3 b , 3 c and 3 d . the first and second sub - layers may be combined differently . fig4 a is a cross - sectional view taken along line i - i ′ of fig1 a for describing further modification example of a 3d semiconductor memory device according to an embodiment of the inventive concept . fig4 b is a magnified view of a portion c of fig4 a . referring to fig4 a and 4b , the entirety of a gate dielectric layer 150 d between the vertical active pattern 130 a and each of the gate patterns 155 l , 155 a 1 , 155 a and 155 u may be substantially extended vertically . that is , the tunnel dielectric layer 141 , charge storage layer 142 and blocking dielectric layer 143 of the gate dielectric layer 150 d may be substantially extended vertically . an extended portion of the gate dielectric layer 150 d may be disposed between the vertical active pattern 130 a and the insulation pattern 110 a . the stack - structure of fig1 a and 1b may have a line shape that is extended in the first direction . unlike this , the stack - structure may include gate patterns having a flat plate shape . this will be described below with reference to the accompanying drawings . fig5 a is a plan view illustrating still further modification example of a 3d semiconductor memory device according to an embodiment of the inventive concept . fig5 b is a cross - sectional view taken along line ii - ii ′ of fig5 a . referring to fig5 a and 5b , a stack - structure according to the modification example may include gate patterns 220 l , 220 a , 220 and 220 u and insulation patterns 210 and 210 u that are stacked alternately and repeatedly . a lowermost gate pattern 220 l in the stack - structure may be a ground selection gate , and an uppermost gate pattern 220 u in the stack - structure may be a string selection gate . the gate pattern 220 a just on the lowermost gate pattern 220 l may be used as a cell gate , a dummy cell gate or a second ground selection gate . the gate patterns 220 between the gate pattern 220 a just on the lowermost gate pattern 220 l and the upper gate pattern 220 u may be used as cell gates . the gate patterns 220 l , 220 a and 220 under a string selection gate , as illustrated in fig5 a and 5b , may have a flat plate shape . the uppermost gate pattern 220 u corresponding to the string selection gate may have a line shape that is extended in the first direction . the uppermost gate pattern 220 u may be provided in plurality , and the uppermost gate patterns 220 u may be extended side by side in the first direction . the bit line 170 may be extended in the second direction and cross over the uppermost gate pattern 220 u . like the uppermost gate pattern 220 u , an uppermost insulation pattern 210 u on the uppermost gate pattern 220 u may also be extended in the first direction . the vertical active pattern 130 a may pass through the stack - structure and be extended into the recess region 120 under it . the lowermost gate pattern 220 l corresponding to the ground selection gate may be disposed on the common source region 105 in the substrate 100 . the entire lower surface of the lowermost gate pattern 220 l may substantially overlap with the common source region 105 . according to the modification example , the gate dielectric layer 150 d may be disposed between the vertical active pattern 130 a and the inner sidewall of an opening 115 passing through the stack - structure . the gate dielectric layer 150 d may be substantially extended vertically . the opening 115 and the recess region 120 may be self - aligned . the gate dielectric layer 150 d may be extended into the recess region 120 . according to an embodiment of the inventive concept , the lower end of the gate dielectric layer 150 d in the recess region 120 may be disposed on a level higher than the lower surface of the recess region 120 . a lower interlayer dielectric 163 may be disposed between the uppermost gate patterns 220 u . an upper surface of the lower interlayer dielectric 163 may be coplanar with an upper surface of the uppermost insulation pattern 210 u . an upper interlayer dielectric 165 may be disposed on the lower interlayer dielectric 163 and the uppermost gate patterns 220 u . the insulation patterns 210 and 210 u may include oxide , nitride and / or oxynitride . the gate patterns 220 l , 220 a , 220 and 220 u may include at least one of a doped semiconductor ( for example , doped silicon ), a metal ( for example , tungsten and others ) or a conductive metal nitride ( for example , a titanium nitride , a tantalum nitride and others ). the elements of the above - described modification examples may be combined or replaced . for example , the capping semiconductor pattern 175 of fig2 a may be disposed on the vertical active pattern 130 or 130 a that has been disclosed in fig1 b , 3 a , 4 a or 5 b . fig6 a to 6h are cross - sectional views taken along line i - i ′ of fig1 a for describing a method of fabricating 3d semiconductor memory device according to an embodiment of the inventive concept . referring to fig6 a , a well region 102 may be formed by providing a first conductive dopant into the substrate 100 . a common source region 105 may be formed by providing a second conductive dopant into the upper portion of the well region 102 . insulation layers 110 and sacrificial layers 112 may be alternately and repeatedly stacked on the common source region 105 . for example , the insulation layers 110 may be formed as oxide layers . the sacrificial layers 112 may be formed of materials having an etch selectivity with respect to the insulation layers 112 . for example , the sacrificial layers 112 may be formed as nitride layers . referring to fig6 b , an opening 115 and a recess region 120 may be formed by sequentially patterning the insulation layers 110 , sacrificial layers 112 and the substrate 100 . the opening 115 may pass through the insulation layers 110 and sacrificial layers 112 , and the recess region 120 may be formed in the common source region 102 under the opening 115 ( i . e ., in a portion of the substrate 100 ). the recess region 120 is self - aligned in the opening 115 by sequentially patterning the insulation layers 110 and sacrificial layers 112 and the substrate 100 . the recess region 120 may pass through the common source region 105 , and the bottom surface of the recess region 120 may be disposed on a level lower than the lower surface of the common source region 105 . therefore , the well region 102 may be exposed to the bottom surface of the recess region 120 , and the common source region 105 may be exposed to the inner sidewall of the recess region 120 . a high concentration region 122 may be formed by providing the first conductive dopant into the well region 102 through the bottom surface of the recess region 120 . the high concentration region 122 of the first conductive dopant may be higher than another portion of the well region 102 . that is , due to the high concentration region 122 , the well region 102 may partially have a high dopant concentration . referring to fig6 c , a semiconductor layer may be conformally formed on the substrate 100 having the opening 115 and the recess region 120 . therefore , the semiconductor layer may be formed to have a substantially uniform thickness on the inner surface of the recess region 120 and an inner sidewall of the opening 115 . the semiconductor layer may contact the inner surface ( i . e ., an inner sidewall and a bottom surface ) of the recess region 120 . the semiconductor layer may be formed in a chemical vapor deposition process and / or an atomic layer deposition process . a filling dielectric layer may be formed on the semiconductor layer to fill the opening 115 . for example , the filling dielectric layer may be formed as an oxide layer . by planarizing the filling dielectric layer and the semiconductor layer until the uppermost insulation layer 110 is exposed , a vertical active pattern 130 and a filling dielectric pattern 132 may be formed in the opening 115 and the recess region 120 . referring to fig6 d , a trench 135 may be formed by sequentially patterning the insulation layers 110 and sacrificial layers 112 , such that insulation patterns 110 a and the sacrificial patterns 112 a being alternately and repeatedly stacked may be formed at a side of the trench 135 . the insulation patterns 110 a and sacrificial patterns 112 a may include the opening 115 . that is , the vertical active patterns 130 may sequentially pass through the insulation patterns 110 a and the sacrificial patterns 112 a being alternately and repeatedly stacked on the substrate 100 . sidewalls of the sacrificial patterns 112 a and the insulation patterns 110 a are exposed to the trench 135 . referring to fig6 e , empty regions 140 may be formed by removing the sacrificial patterns 112 a exposed to the trench 135 . each of the empty regions 140 corresponds to a region from which the each sacrificial pattern 112 a is removed . the empty regions 140 may expose some portions of the sidewall of the vertical active pattern 130 , respectively . referring to fig6 f , a gate dielectric layer 150 may be conformally formed on the substrate 100 having the empty regions 140 . therefore , the gate dielectric layer 150 may be conformally formed on the inner surfaces of the empty regions 140 . the gate dielectric layer 150 , as described above with reference to fig1 b and 1c , may include the tunnel dielectric layer , the charge storage layer and the blocking dielectric layer . a gate conductive layer 155 filling the empty regions 140 may be formed on the substrate 100 having the gate dielectric layer 150 . the gate conductive layer 155 may also be formed in the trench 135 . herein , the gate conductive layer 155 may partially fill the trench 135 . therefore , a space surrounded by the gate conductive layer 155 may be formed in the trench 135 . a bottom surface of the space may be lower than an inner - upper surface of the lowermost empty region 140 . referring to fig6 g , the gate patterns 155 l , 155 a 1 , 155 a and 155 u respectively filling the empty regions 140 may be formed by etching the gate conductive layer 155 . the gate patterns 155 l , 155 a 1 , 155 a and 155 u are separated by the etching process of the gate conductive layer 155 . according to an embodiment of the inventive concept , the etching process of the gate conductive layer 155 may be an isotropic etching process . the insulation patterns 110 a and the gate patterns 155 l , 155 a 1 , 155 a and 155 u , being alternately and repeatedly stacked on the substrate 100 , may be included in a stack - structure . subsequently , a device isolation insulation layer 160 may be formed to fill the trench 135 . referring to fig6 h , the device isolation insulation layer 160 and the gate dielectric layer 150 may be planarized until the uppermost insulation pattern among the insulation patterns 110 a is exposed . therefore , a device isolation pattern 160 a may be formed in the trench 135 . subsequently , by forming the interlayer dielectric 165 , contact plug 167 and bit line 170 of the fig1 b on the substrate 100 , the 3d semiconductor memory device that has disclosed in fig1 a , 1 b and 1 c may be implemented . according to the above - described 3d semiconductor memory device , the opening 115 and the recess region 120 can be formed in self - alignment by sequentially patterning the insulation layers 110 , the sacrificial layers 112 and the substrate 100 ( i . e . the common source region 105 ). therefore , the 3d semiconductor memory device can be implemented which has excellent reliability and is optimized for high integration . next , a method of fabricating the 3d semiconductor memory device that has been disclosed in fig2 a will be described below with reference to the accompanying drawings . the method may include the methods that have been described above with reference to fig6 a and 6b . fig7 a to 7d are cross - sectional views taken along line i - i ′ of fig1 a for describing a modification example of a method of fabricating 3d semiconductor memory device according to an embodiment of the inventive concept . referring to fig6 b and 7a , a protection dielectric layer 173 may be conformally formed on the substrate 100 having the opening 115 and the recess region 120 , and the protection dielectric layer 173 may be etched by a blanket anisotropic etching process until the bottom surface of the recess region 120 is exposed . as illustrated in fig7 a , therefore , the protection dielectric layer 173 may be formed on the sidewalls of the recess region 120 and the opening 115 . the protection dielectric layer 173 may include a dielectric material having an etch selectivity with respect to the sacrificial layer 112 . for example , the protection dielectric layer 173 may be formed of oxide . subsequently , a semiconductor layer may be formed , a filling dielectric layer may be formed on the semiconductor layer , and the filling dielectric layer and the semiconductor layer may be planarized . therefore , the vertical active pattern 130 and the filling dielectric pattern 132 may be formed in the opening 115 and the recess region 120 . the vertical active pattern 130 may contact the bottom surface of the recess region 120 . the protection dielectric layer 173 may be disposed between the vertical active pattern 130 and the inner sidewalls of the opening 115 and the recess region 120 . referring to fig7 b , the upper ends of the vertical active pattern 130 , filling dielectric pattern 132 and protection dielectric layer 175 may be recessed lower than the upper surface of the uppermost insulation layer 110 . subsequently , a capping semiconductor layer filling the opening 110 may be formed on the substrate 100 , and a capping semiconductor pattern 175 may be formed by planarizing the capping semiconductor layer until the uppermost insulation layer 110 is exposed . the capping semiconductor pattern 175 may cover the recessed upper ends of the vertical active pattern 130 , filling dielectric pattern 132 and protection dielectric layer 175 . subsequently , the trench 135 may be formed by sequentially patterning the insulation layers 110 and the sacrificial layers 112 . in this case , as described above , the insulation patterns 110 and the sacrificial patterns 112 a that are alternately and repeatedly stacked may be formed at a side of the trench 135 . referring to fig7 c , the sacrificial patterns 112 a exposed to the trench 135 may be removed . therefore , the empty regions 140 may be formed which respectively exposes some portions of the protection dielectric layer 173 disposed on the sacrificial patterns 112 a and the vertical active patterns 130 . as described above , the protection dielectric layer 173 has an etch selectivity with respect to the sacrificial patterns 112 a , and thus it can protect the vertical active pattern 130 from a process of removing the sacrificial patterns 112 a . the protection dielectric layer 173 may be used as an etch stop layer in the process of removing the sacrificial patterns 112 a . subsequently , the exposed portions of the protection dielectric layer 173 may be removed . therefore , the empty regions 140 may expose some portions of the side wall of the vertical active pattern 130 , respectively . when removing the exposed portions of the protection dielectric layer 173 , the protection dielectric patterns 173 a may be formed between the vertical active pattern 130 and the insulation patterns 110 a and between the vertical active pattern 130 and the inner sidewall of the recess region 120 . the protection dielectric patterns 173 a correspond to remaining portions of protection dielectric layer 173 . referring to fig7 d , the gate dielectric layer 150 may be conformally formed on the substrate 100 having the empty regions 140 , and the gate patterns 155 l , 155 a 1 , 155 a and 155 u respectively filling the empty regions 140 may be formed . afterwards , the device isolation pattern 160 a filling the trench 135 may be formed . subsequently , by forming the interlayer dielectric 165 , contact plug 167 and bit line 170 of fig2 a , the 3d semiconductor memory device of fig2 a can be implemented . the features of a method , that fabricates the 3d semiconductor memory device that has been disclosed in fig2 b , may have a process of forming the lower surface of the recess region 120 higher than the lower surface of the common source region 105 and a process of forming the counter - doped region 122 a by counter - doping the common source region 105 under the bottom surface of the recess region 120 with the first conductive dopant . other processes may be the same as the processes that have been described above with reference to fig7 a to 7d . next , a method of fabricating the 3d semiconductor memory device that has been disclosed in fig3 a will be described below with reference to the accompanying drawings . the method may include the methods that have been described above with reference to fig6 a and 6b . fig8 a to 8f are cross - sectional views taken along line i - i ′ of fig1 a for describing other modification example of a method of fabricating 3d semiconductor memory device according to an embodiment of the inventive concept . referring to fig6 b and 8a , a first sub - layer 147 may be conformally formed on the substrate 100 having the opening 115 and the recess region 120 . the first sub - layer 147 may be conformally formed on the inner sidewall of the opening 115 and the inner surface of the recess region 120 . a first semiconductor layer 121 may be conformally formed on the substrate 100 having the first sub - layer 147 . referring to fig8 b , portions of the first sub - layer 147 and the first semiconductor layer 121 disposed on the bottom surface of the recess region 120 may be removed . at this point , portions of the first sub - layer 147 and the first semiconductor layer 121 disposed outside opening 115 may also be removed . therefore , the first sub - layer 147 and the first semiconductor pattern 123 that are sequentially stacked on the sidewalls of the recess region 120 and opening 115 may be formed , the first semiconductor pattern 123 correspond to a portion of the first semiconductor layer 121 . according to an embodiment of the inventive concept , by blanket - anisotropic - etching the first semiconductor layer 121 and the first sub - layer 147 until the bottom surface of the recess region 120 is exposed , the first semiconductor pattern 123 may be formed . the first semiconductor pattern 123 may not contact the inner surface of the recess region 120 by the first sub - layer 147 . referring to fig8 c , subsequently , by isotropic - etching the first sub - layer 147 , at least one portion of the inner sidewall of the recess region 120 may be exposed . at this point , a portion of the first semiconductor pattern 123 in the recess region 120 may also be etched . referring to fig8 d , subsequently , a second semiconductor layer may be conformally formed on the substrate 100 , a filling dielectric layer filling the opening 115 may be formed on the second semiconductor layer . the second semiconductor layer may contact the first semiconductor pattern 123 , and also the second semiconductor layer may contact the bottom surface and exposed inner sidewall of the recess region 120 . by planarizing the second semiconductor layer and the filling dielectric layer , a second semiconductor pattern 124 and a filling dielectric pattern 132 may be formed in the opening 115 and the recess region 120 . the second semiconductor pattern 124 may contact the bottom surface and inner sidewall of the recess region 120 and the first semiconductor pattern 123 . the first and second semiconductor patterns 123 and 124 may configure a vertical active pattern 130 a . referring to fig8 e , subsequently , the trench 135 , the insulation patterns 110 a and the sacrificial patterns 112 may be formed by sequentially patterning the insulation layers 110 and the sacrificial layers 112 . the empty regions 140 may be formed by removing the sacrificial patterns 112 . at this point , the empty regions 140 may expose some portions of the first sub - layer 147 , respectively . referring to fig8 f , a second sub - layer 149 may be conformally formed on the substrate 100 having the empty regions 140 . the second sub - layer 149 may be conformally formed on the inner surfaces of the empty regions 140 . the second sub - layer 149 may contact the first sub - layer 147 exposed to the empty regions 140 . the first and second sub - layers 147 and 149 may be included in the gate dielectric layer 150 a . the first sub - layer 147 may include at least a portion of the tunnel dielectric layer , and the second sub - layer 149 may include at least a portion of the blocking dielectric layer . herein , one of the first and second sub - layers 147 and 149 may include the charge storage layer . according to an embodiment of the inventive concept , the first and second sub - layers 147 and 149 may be the same as the layers that have been described above with reference to fig3 b . unlike this , the first and second sub - layers 147 and 149 may be replaced with the first and second sub - layers 147 a and 149 a of the fig3 c , respectively . unlike this , the first and second sub - layers 147 and 149 may be replaced with the first and second sub - layers 149 b and 149 c of the fig3 c , respectively . subsequently , the gate patterns 155 l , 155 a 1 , 155 a and 155 u respectively filling the empty regions 140 may be formed , and the device isolation pattern 160 a filling the trench 135 may be formed . subsequently , the interlayer dielectric 165 , the contact plug 167 and the bit line 170 that have been disclosed in fig3 a may be formed . next , a method of fabricating the 3d semiconductor memory device that has been disclosed in fig4 a and 4b will be described below with reference to the accompanying drawings . the method may include the methods that have been described above with reference to fig6 a and 6b . fig9 a to 9d are cross - sectional views taken along line i - i ′ of fig1 a for describing still other modification example of a method of fabricating 3d semiconductor memory device according to an embodiment of the inventive concept . referring to fig6 b to 9a , a gate dielectric layer 150 d may be conformally formed on the substrate 100 having the opening 115 and the recess region 120 . a first semiconductor layer may be conformally formed on the gate dielectric layer 150 d . subsequently , the first semiconductor layer and the gate dielectric layer 150 d may be etched by a blanket - anisotropic - etching process until the bottom of the recess region 120 is exposed , such that a first semiconductor pattern 123 may be formed in the opening 115 and the recess region 120 . at this point , the gate dielectric layer 150 d may also be restrictively disposed in the opening 115 and the recess region 120 . the first semiconductor pattern 123 may not contact the side wall of the opening 115 and the inner surface of the recess region 120 by the gate dielectric layer 150 d . referring to fig9 b , subsequently , a second semiconductor may be conformally formed over the substrate 100 , and a filling dielectric layer may be formed on the second semiconductor layer . by planarizing the filling dielectric layer and the second semiconductor layer , a second semiconductor pattern 124 and a filling dielectric pattern 132 may be formed in the opening 115 and the recess region 120 . the first and second semiconductor patterns 123 and 124 may configure a vertical active pattern 130 a . subsequently , a trench 135 , insulation patterns 110 a and sacrificial patterns 112 a may be formed by sequentially patterning the insulation layers 110 and the sacrificial layers 112 . according to the modification example , a portion of the lowermost insulation layer among the insulation layers 110 may remain under the trench 135 . referring to fig9 c , empty regions 140 may be formed by removing the sacrificial patterns 112 a . the empty regions 140 may expose the gate dielectric layer 150 d . particularly , the blocking dielectric layer 143 ( see fig4 b ) in the gate dielectric layer 150 d may be exposed . subsequently , a gate conductive layer 155 filling the empty regions 140 may be formed on the substrate 100 . referring to fig9 d , by removing the gate conductive layer outside the empty regions 140 , gate patterns 155 l , 155 a 1 , 155 a and 155 u filling the empty regions 140 may be formed . subsequently , the device isolation pattern 160 a filling the trench 135 may be formed , and the interlayer dielectric 165 , contact plug 167 and bit line 170 of fig4 a may be formed . thus , the 3d semiconductor memory device of fig4 a and 4b can be implemented . next , a method of fabricating the 3d semiconductor memory device of fig5 a and 5b will be described below with reference to the accompanying drawings . fig1 a to 10c are cross - sectional views taken along line i - i ′ of fig1 a for describing even other modification example of a method of fabricating 3d semiconductor memory device according to an embodiment of the inventive concept . referring to fig1 a , insulation layers 210 and gate layers 220 may be alternately and repeatedly stacked on the common source region 105 in the substrate 100 . the insulation layers 210 and gate layers 220 l , 220 a and 220 may have a flat plate shape . referring to fig1 b , an uppermost gate pattern 220 u and an uppermost insulation pattern 210 u may be formed by patterning an uppermost insulation layer and an uppermost gate layer . the uppermost gate pattern 220 u and the uppermost insulation pattern 210 u may have a line shape that is extended in one direction as illustrated in fig5 a . a lower interlayer dielectric 163 may be formed on the substrate 100 , and the lower interlayer dielectric 163 may be planarized . an opening 115 and a recess region 120 may be formed by sequentially patterning the uppermost insulation pattern 210 u , the uppermost gate pattern 220 u , the insulation layers 210 , the gate layers 220 l , 220 a and 220 and the common source region 105 . the recess region 120 may be formed in self - alignment in the opening 115 . by providing a first conductive dopant through the bottom surface of the recess region 120 , a high concentration region 122 may be formed . subsequently , a gate dielectric layer 150 d may be conformally formed over the substrate 100 , and a first semiconductor layer may be conformally formed on the gate dielectric layer 150 d . by blanket - isotropic - etching the first semiconductor layer and the gate dielectric layer 150 d until the bottom surface of the recess region 120 is exposed , a first semiconductor pattern 123 may be formed in the opening 115 and the recess region 120 . referring to fig1 c , a second semiconductor layer may be conformally formed over the substrate 100 , and a filling dielectric layer may be formed on the second semiconductor . by planarizing the filling dielectric layer and the second semiconductor layer , a second semiconductor pattern 124 and a filling dielectric pattern 132 may be formed in the opening 115 and the recess region 120 . the first and second semiconductor patterns 123 and 124 may configure a vertical active pattern 130 a . subsequently , the tipper dielectric layer 165 , contact plug 167 and bit line 170 of fig5 b may be formed . thus , the 3d semiconductor memory device of fig5 a and 5b can be implemented . according to the above - described method , the uppermost gate pattern 220 u may be formed , and thereafter the vertical active pattern 130 a may be formed . unlike this , after the opening 115 , the recess region 120 and the vertical active pattern 130 a may be formed , and then the uppermost gate pattern 220 u may be formed . when forming the uppermost gate pattern 220 u , a stack - structure having a line shape may be formed by sequentially patterning the gate layers 220 , 220 a and 220 l and insulation layers 110 under the uppermost gate pattern 220 u . in this case , the 3d semiconductor memory device of fig4 a and 4b can be implemented . in other words , the 3d semiconductor memory device of fig4 a and 4b may be implemented in the method that has been described above with reference to fig9 a to 9d or a modified method of a portion of the fabricating method of fig1 a to 10c . fig1 is a cross - sectional view illustrating a 3d semiconductor memory device according to another embodiment of the inventive concept . referring to fig1 , a well region 102 doped with a first conductive dopant may be disposed in a substrate 100 . a stack - structure may be disposed on the well region 102 . the stack - structure may include insulation patterns 110 a and gate patterns 155 l , 155 a 1 , 155 a and 155 u that are alternately and repeatedly stacked on the well region 102 . a plurality of the stack - structures may be disposed on the well region 102 . the stack - structures may be spaced apart from each other . as illustrated in fig1 a , the stack - structures may be extended in parallel . a vertical active pattern 280 may pass through the stack - structure . also , the vertical active pattern 280 may be extended into a recess region 120 that is formed in the substrate 100 under the vertical active pattern 280 . the vertical active pattern 280 may include a lower active pattern 250 and an upper active pattern 270 that are sequentially stacked . the lower active pattern 250 may fill the recess region 120 . the upper active pattern 270 may contact the inner surface ( i . e ., inner sidewall and bottom surface ) of the recess region 120 . the lower active pattern 250 is disposed in the recess region 120 and contacts the well region 102 . the upper surface of the lower active pattern 250 may be disposed on a level higher than that of the upper surface of the substrate 100 . according to an embodiment of the inventive concept , as illustrated in fig1 , the upper surface of the lower active pattern 250 may be higher than the lower surface of the lowermost gate pattern 155 l and lower than the upper surface of the lowermost gate pattern 155 l . however , the inventive concept is not limited thereto . the upper active pattern 270 contacts the upper surface of the lower active pattern 250 . according to an embodiment of the inventive concept , the lower active pattern 250 may have a pillar shape , and the upper active pattern 270 may have a pipe shape or a macaroni shape . in this case , the inside of the upper active pattern 270 may be filled with a filling dielectric pattern 132 . the lower and upper active patterns 250 and 270 may include a semiconductor material . for example , the lower and upper active patterns 250 and 270 may include the same semiconductor material as that of the substrate 100 . as an example , when the substrate 100 is a silicon substrate , the lower and upper active patterns 250 and 270 may include silicon . according to an embodiment of the inventive concept , the lower active pattern 250 may have a single crystalline state . the upper active pattern 270 may have a poly - crystalline state . the lower active pattern 250 may be doped with a dopant having the same type as that of the well region 102 . the upper active pattern 270 may be doped with a dopant having the same type as that of the well region 102 , or may have an undoped state . a high concentration region 122 may be disposed under the bottom surface of the recess region 120 . the high concentration region 122 may correspond to a portion of the well region 102 , and it may have a higher dopant concentration than another portion of the well region 102 . a gate dielectric layer 150 may be disposed between a sidewall of the vertical active pattern 280 and each of the gate patterns 155 l , 155 a 1 , 155 a and 155 u . as described above in first embodiment of the inventive concept , the gate dielectric layer 150 may be extended horizontally and cover the upper surface and lower surface of each of the gate patterns 155 l , 155 a 1 , 155 a and 155 u . according to an embodiment of the inventive concept , a common source regions 105 a may be disposed in the substrate 100 of the both sides of the stack - structure , respectively . the common source region 105 a may be laterally separated from the lower active pattern 250 . the common source region 105 a is doped with a second conductive dopant . a device isolation pattern 160 a may be disposed between the stack - structures . the common source region 105 a may be disposed under the device isolation pattern 160 a . in operating of the 3d semiconductor memory device , a horizontal channel may be generated in the well region 102 under the lowermost gate pattern 155 l . the common source region 105 a may be electrically connected to vertical channels that are formed in the vertical active pattern 280 by the horizontal channel in the well region 102 . a contact plug 167 passing through the interlayer dielectric 165 may be connected to the upper end of the upper active pattern 270 . a drain doped with the second conductive dopant may be disposed in the upper portion of the upper active pattern 270 . the lower surface of the drain may be disposed on a level adjacent to the upper surface of the uppermost gate pattern 155 u in the stack - structure . according to the above - described 3d semiconductor memory device , the lower active pattern 250 included in the vertical active pattern 280 fills the recess region 120 to contact the well region 102 . therefore , reliability for the operations of a vertical cell string can be improved . particularly , reliability for the erasing operation of cell transistors can be enhanced . also , the vertical active pattern 280 may be divided into the lower active pattern 250 and the upper active pattern 270 . accordingly , an independent and additional process may be performed in the lower active pattern 250 . for example , a dopant concentration may be adjusted in the lower active pattern 250 . thus , it is very easy to control the characteristic of the 3d semiconductor memory device . as a result , the 3d semiconductor memory device can be implemented which has excellent reliability and is optimized for high integration . next , the modification examples of the 3d semiconductor memory device will be described below with reference to the accompanying drawings . fig1 a is a cross - sectional view illustrating a modification example of a 3d semiconductor memory device according to another embodiment of the inventive concept . referring to fig1 a , a common source region 105 may be extended to the substrate 100 under the stack - structures . for example , the entire lower surface of the lowermost gate pattern 155 l may substantially overlap with the common source region 105 . in this case , the bottom of the recess region 120 may be disposed on a level lower than the lower surface of the common source region 105 . the common source region 105 may contact a sidewall of the lower active pattern 250 . fig1 b is a cross - sectional view illustrating other modification example of a 3d semiconductor memory device according to another embodiment of the inventive concept . referring to fig1 b , a vertical active pattern 280 a may include a lower active pattern 250 and an upper active pattern 270 a that are sequentially stacked . a gate dielectric layer 150 a may be disposed between the upper active pattern 270 a and each of the gate patterns 155 a 1 , 155 a and 155 u disposed next to the upper active pattern 270 a . the gate dielectric layer 150 a may include a first and a second sub - layers 147 and 149 . as described above in first embodiment of the inventive concept , the first sub - layer 147 may be extended vertically and be disposed between the upper active pattern 270 a and the insulation pattern 110 a . the second sub - layer 149 may be extended horizontally and cover the lower surface and upper surface of each of the gate patterns 155 a 1 , 155 a and 155 u . when the upper surface of the lower active pattern 250 is disposed on a level between the levels of the lower and upper surfaces of the lowermost gate pattern 155 l , the first sub - layer 147 may not exist between the lower active pattern 250 and the lowermost gate pattern 155 l . the upper active pattern 270 a may include a first semiconductor pattern 265 and a second semiconductor pattern 267 . the first semiconductor pattern 265 may be disposed between the first sub - layer 147 and the second semiconductor pattern 267 . the first semiconductor pattern 265 may be separated from the upper surface of the lower active pattern 250 by a portion of the first sub - layer 147 . the second semiconductor pattern 267 contacts the first semiconductor pattern 265 . also , the second semiconductor pattern 267 contacts the upper surface of the lower active pattern 250 . the upper surface of the lower active pattern 250 may be divided into a center portion 252 c contacting the second semiconductor pattern 267 and an edge portion 252 e contacting the first sub - layer 147 . herein , the center portion 252 c of the upper surface of the lower active pattern 250 may be disposed on a level lower than that of the edge portion 252 e . the upper active pattern 270 a including the first and second semiconductor patterns 265 and 267 may have a pipe shape or a macaroni shape . in this case , the inside of the upper active pattern 270 a may be filled with a filling dielectric pattern 132 . the first and second semiconductor patterns 265 and 267 may have a poly - crystalline state . in the modification example , the first and second sub - layers 147 and 149 may be replaced by the first and second sub - layers 147 a and 149 a of fig3 c or the first and second sub - layers 147 b and 149 b of fig3 c . unlike this , as described above in first embodiment of the inventive concept , the first and second sub - layers 147 and 149 may be formed by another combination of a tunnel dielectric layer , a charge storage layer and a blocking dielectric layer . fig1 c is a cross - sectional view illustrating still other modification example of a 3d semiconductor memory device according to another embodiment of the inventive concept . referring to fig1 c , at least edge portion of the upper surface of the lower active pattern 250 may be disposed on a level higher than the upper surface of the lowermost gate pattern 155 l . in this case , an oxide layer 255 may be disposed between the sidewall of the lower active pattern 250 and the lowermost gate pattern 155 l . the oxide layer 255 may include oxide formed by oxidizing the sidewall of the lower active pattern 250 . therefore , the width of a first portion of the lower active pattern 250 next to the oxide layer 255 may be less than that of a second portion of the lower active pattern 250 disposed in the recess region 120 . when the gate dielectric layer 150 a includes the first and second sub - layers 147 and 149 , the oxide layer 255 and a portion of the second sub - layer 149 may be disposed between the sidewall of the lower active pattern 250 and the lowermost gate pattern 155 l . in other words , the first sub - layer 147 may not exist between the sidewall of the lower active pattern 250 and the lowermost gate pattern 155 l . according to an embodiment of the inventive concept , when the first sub - layer 147 includes a charge storage layer , the charge storage layer may not exist between the sidewall of the lower active pattern 250 and the lowermost gate pattern 155 l . therefore , the reliability of a ground selection transistor including the lowermost gate pattern 155 l can be improved . moreover , the lower active pattern 250 may have a single crystalline state . accordingly , the reliability of the ground selection transistor can be more enhanced . fig1 d is a cross - sectional view illustrating even other modification example of a 3d semiconductor memory device according to another embodiment of the inventive concept . referring to fig1 d , at least the edge portion of the upper surface of a lower active pattern 250 may be disposed on a level higher than the upper surface of a gate pattern 155 a 1 that is stacked secondarily from the substrate 100 and lower than the lower surface of a gate pattern that is stacked thirdly from the substrate 100 . the secondarily - stacked gate pattern 155 a 1 and the thirdly - stacked gate pattern are disposed over the lowermost gate pattern 155 l . in this case , an oxide layer 255 may also be disposed between the secondarily - stacked gate pattern 155 a 1 and the side wall of the lower active pattern 250 . according to the modification example , a transistor including the secondarily - stacked gate pattern 155 a 1 may be used as a dummy transistor or a second ground selection transistor . in this case , a cell gate ( for example , the thirdly - stacked gate pattern 155 a ) adjacent to the secondarily - stacked gate pattern 155 a 1 may correspond to a dummy cell gate . as described above , a dummy cell transistor including the dummy cell gate has the same type as that of a cell transistor storing data , but it may not serve as a cell transistor . as an example , in operating of the cell string , the dummy cell transistor may perform only a turn - on / off function . however , the inventive concept is not limited thereto . the thirdly - stacked gate pattern may be used as a cell transistor . fig1 e is a cross - sectional view illustrating yet other modification example of a 3d semiconductor memory device according to another embodiment of the inventive concept . referring to fig1 e , the entirety of a gate dielectric layer 150 d between the sidewall of the upper active pattern 270 a and each of the gate patterns 155 a 1 , 155 a and 155 u may be substantially extended vertically and be disposed between an upper active pattern 270 a and an insulation pattern 110 a . in this case , only an oxide layer 255 may be disposed between the sidewall of the lower active pattern 250 and the lowermost gate pattern 155 l . fig1 f is a cross - sectional view illustrating further modification example of a 3d semiconductor memory device according to another embodiment of the inventive concept . referring to fig1 f , protection dielectric patterns 173 a may be disposed between the upper active pattern 270 a and the insulation patterns 110 a . in a fabricating process , the protection dielectric pattern 173 a may include a dielectric material for protecting the upper active pattern 270 . according to an embodiment of the inventive concept , the protection dielectric pattern 173 a may not exist between the lower active pattern 250 and the inner sidewall of the recess region 120 . the elements of the above - described modification examples may be combined without clash or replaced . for example , the common source region 105 a of fig1 may be replaced with the common source region 105 of fig1 b to 12f . for example , in the 3d semiconductor memory devices of fig1 and 12a to 12 f , the heights of the upper surfaces of the lower active patterns 250 may be replaced . fig1 a to 13e are cross - sectional views for describing a method of fabricating 3d semiconductor memory device according to another embodiment of the inventive concept . referring to fig1 a , a well region 102 may be formed by providing a first conductive dopant to the substrate 100 . insulation layers 110 and sacrificial layers 112 that are alternately and repeatedly stacked may be formed on the well region 102 . a recess region 120 and an opening 115 that are sequentially stacked may be formed by sequentially patterning the insulation layers 110 , the sacrificial layers 112 and the substrate 100 . the opening 115 may pass through the insulation layers 110 and the sacrificial layers 112 , and the recess region 120 may be self - aligned in the opening 115 and be formed in the substrate 100 . the recess region 120 may expose the well region 102 . referring to fig1 b , a high concentration region 122 may be formed by providing the first conductive dopant through the bottom of the recess region 120 . a lower active pattern 250 filling the recess region 120 may be formed . the upper surface of the lower active pattern 250 may be higher than the upper surface of the substrate 100 . therefore , a portion of the lower active pattern 250 may fill the lower portion of the opening 115 . the lower active pattern 250 contacts the well region 102 . the lower active pattern 250 may be formed in a selective epitaxial growth process that uses the substrate 100 exposed by the recess region 120 as a seed layer . therefore , the lower active pattern 250 may be formed in a single crystalline state . the lower active pattern 250 may be formed in a pillar shape . the lower active pattern 250 may be doped with the first conductive dopant . the lower active pattern 250 may be doped by an in - situ process when the selective epitaxial growth process is performed . unlike this , the lower active layer 250 may be doped by an ion - implanting process . referring to fig1 c , a semiconductor layer may be conformally formed on the substrate 100 having the lower active pattern 250 , and a filling dielectric layer filling the opening 115 may be formed on the semiconductor layer . the semiconductor layer may be conformally formed on the inner sidewall of the opening 115 and the upper surface of the lower active pattern 250 . the semiconductor layer may contact the lower active pattern 250 . the semiconductor layer may be formed in a chemical vapor deposition process and / or an atomic layer deposition process . therefore , the semiconductor layer may be formed in a poly - crystalline state . by planarizing the filling dielectric layer and the semiconductor layer , an upper active pattern 270 and a filling dielectric pattern 132 may be formed in the opening 115 . the lower and upper active patterns 250 and 270 may configure a vertical active pattern 280 . subsequently , a trench 135 , insulation patterns 110 a and sacrificial patterns 110 a may be formed by sequentially patterning the insulation layers 110 and the sacrificial layers 112 . the vertical active pattern 280 passes through the insulation patterns 110 a and the sacrificial patterns 112 a . subsequently , by providing a second conductive dopant into the well region 102 under the trench 135 , a common source region 105 a may be formed . referring to fig1 d , by removing sacrificial patterns 112 a exposed to the trench 135 , empty regions 140 may be formed . according to an embodiment of the inventive concept , at least a portion of an lowermost empty regions 140 may expose a portion of the sidewall of the lower active pattern 250 . a gate dielectric layer 150 may be conformally formed on the substrate 100 having the empty regions 140 , and a gate conductive layer 155 filling the empty regions 140 may be formed . referring to fig1 e , gate patterns 155 l , 155 a 1 , 155 a and 155 u , that are respectively disposed in the empty regions 140 , may be formed by etching the gate conductive layer 155 . subsequently , a device isolation pattern 160 a filling the trench 135 may be formed . the 3d semiconductor memory device of fig1 may be implemented by forming the interlayer dielectric 165 , contact plug 167 and bit line 170 of fig1 . according to the above - described 3d semiconductor memory device , the opening 115 and the recess region 120 are formed in self - alignment , and the lower active pattern 250 fills the recess region 120 to contact the well region 102 . after , the lower active pattern 250 is formed , and then the upper active pattern 270 may be formed . therefore , the doping concentration of the lower active pattern 250 may be independently adjusted . as a result , the 3d semiconductor memory device having superior reliability can be implemented . the features of the method of fabricating 3d semiconductor memory device that is illustrated in fig1 a will be described below with reference to fig1 . fig1 is a cross - sectional view illustrating a modification example of a method of fabricating 3d semiconductor memory device according to another embodiment of the inventive concept . referring to fig1 , a second conductive dopant is injected into a substrate 100 having a well region 102 , such that a common source region 105 may be formed . insulation layers 110 and sacrificial layers 112 that are alternately and repeatedly stacked may be formed on the common source region 105 . an opening 115 and a recess region 120 may be formed by sequentially patterning the insulation layers 110 , the sacrificial layers 112 and the substrate 100 . the recess region 120 may pass through the common source region 105 , and thus the bottom surface of the recess region 120 may be lower than the lower surface of the common source region 105 . the bottom surface of the recess region 120 may expose the well region 102 , and the inner sidewall of the recess region 120 may expose the common source region 105 . successive processes may be performed identically to the process that has been described above with reference to fig1 a through fig1 e . however , the process of forming the common source region 105 a that has been described above with reference to fig1 c may be omitted . fig1 a to 15f are cross - sectional views illustrating other modification example of a method of fabricating 3d semiconductor memory device according to another embodiment of the inventive concept . a fabricating method according to the modification example may include the method that has been described above with reference to fig1 . referring to fig1 and 15a , a lower active pattern 250 filling the recess region 120 may be formed on the substrate 100 having the opening 115 and the recess region 120 . the lower active pattern 250 may be formed identically to the process that has been described above with reference to fig1 b . the level of the upper surface of the lower active pattern 250 may be adjusted . in fig1 a , the upper surface of the lower active pattern 250 may be higher than the level of the upper surface of a lowermost sacrificial layer and lower than the level of the lower surface of a sacrificial layer just on the lowermost sacrificial layer . a first sub - layer 147 may be conformally formed on the substrate 100 having the lower active pattern 250 . a first semiconductor layer 264 may be conformally formed on the first sub - layer 147 . the first semiconductor layer 264 may be formed in a chemical vapor deposition process and / or an atomic layer deposition process . the first semiconductor layer 264 may be formed in a poly - crystalline state . referring to fig1 b , the first semiconductor layer 264 and the first sub - layer 147 may be blanket - anisotropic - etched until the upper surface of the lower active pattern 250 is exposed . therefore , a first semiconductor pattern 265 may be formed in the opening 115 . according to an embodiment of the inventive concept , the center portion of the exposed upper surface of the lower active pattern 250 may be recessed lower than the edge portion of the upper surface of the lower active pattern 250 . referring to fig1 c , a second semiconductor layer may be conformally formed on the substrate 100 having the first semiconductor pattern 265 , and a filling dielectric layer may be formed on the second semiconductor layer . the second semiconductor layer may contact the first semiconductor pattern 265 and the center portion of the upper surface of the lower active pattern 250 . by planarizing the filling dielectric layer and the second semiconductor layer , a second semiconductor pattern 267 and a filling dielectric pattern 132 may be formed in the opening 115 . the first and second semiconductor patterns 265 and 267 may configure an upper active pattern 270 a , and the lower and upper active patterns 250 and 270 a may configure a vertical active pattern 280 a . subsequently , a trench 135 , insulation patterns 110 a and sacrificial patterns 112 a may be formed by sequentially patterning the insulation layers 110 and the sacrificial layers 112 . referring to fig1 d , empty regions 140 may be formed by removing the sacrificial patterns 112 a . according to an embodiment of the inventive concept , the lowermost empty region of the empty regions 140 may expose the sidewall of the lower active pattern 250 , and empty regions on the lowermost empty region may expose the first sub - layer 147 . however , the inventive concept is not limited thereto . the number of empty regions for exposing the sidewall of the lower active pattern 250 may vary with the height of the edge portion of the upper surface of the lower active pattern 250 . referring to fig1 e , an oxide layer 255 may be formed by performing an oxidizing process in the exposed sidewall of the lower active pattern 250 . when the lower active pattern 250 is formed of silicon , the oxide layer 255 may be formed of a silicon oxide . the sidewall of the upper active pattern 270 a may not be oxidized by the first sub - layer 147 . referring to fig1 f , subsequently , a second sub - layer 149 may be conformally formed over the substrate 100 , and gate patterns 155 l , 155 a 1 , 155 a and 155 u respectively filling the empty regions 140 may be formed . subsequently , an isolation pattern 160 a , an interlayer dielectric layer 165 , a contact plug 167 and a bit line 170 may be formed . therefore , the 3d semiconductor memory device of fig1 c can be implemented . in the fabricating method of fig1 a to 15f , the level of the upper surface of the lower active pattern 250 may be higher than the level of the upper surface of a sacrificial layer that is stacked secondarily from the upper surface of the substrate 100 and lower than the level of the lower surface of a thirdly - stacked sacrificial layer . in this case , the 3d semiconductor memory device of fig1 d can be implemented . in the fabricating method of fig1 a to 15f , when the level of the upper surface of the lower active pattern 250 is disposed between the levels of the upper and lower surfaces of the lowermost sacrificial layer and the oxidizing process is omitted , the 3d semiconductor memory device of fig1 b can be implemented . in the fabricating method of fig1 a to 15f , when the first sub - layer 147 is replaced by the gate dielectric layer 150 d and forming of the second sub - layer 149 is omitted , the 3d semiconductor memory device of fig1 e can be implemented . next , a method of fabricating the 3d semiconductor memory device that is illustrated in fig1 f will be described below with reference to the accompanying drawings . the method may include the method that has been described above with reference to fig1 . fig1 a and 16b are cross - sectional views illustrating still other modification example of a method of fabricating 3d semiconductor memory device according to another embodiment of the inventive concept . referring to fig1 and 16a , after a lower active pattern 250 may be formed , a protection dielectric layer may be conformally formed on the substrate 100 . the protection dielectric layer may be blanket - anisotropic - etched until the upper surface of the lower active pattern 250 is exposed . therefore , a protection dielectric layer 173 may be formed to have a spacer shape in the sidewall of the opening 115 . subsequently , a semiconductor layer may be conformally formed , and a filling dielectric layer may be formed . the filling dielectric layer and the semiconductor layer may be planarized , such that an upper active pattern 270 and a filling dielectric pattern 132 may be formed in the opening 115 . subsequently , the upper ends of the protection dielectric layer 173 , upper active pattern 270 and filling dielectric pattern 132 may be recessed , and then a capping semiconductor pattern 175 may be formed . the capping semiconductor pattern 175 may be formed in the same process as the process that has been described above with reference to fig7 b . referring to fig1 b , a trench 135 , insulation patterns 110 a and sacrificial patterns 112 a may be formed by sequentially patterning insulation layers 110 and sacrificial layers 112 . empty regions 140 may be formed by removing the sacrificial patterns 112 a . at this point , the protection dielectric layer 173 may be used an etch stop layer . subsequently , by removing some portions of the protection dielectric layer 173 exposed to the empty regions 140 , some portions of the sidewall of the upper active pattern 270 may be exposed . subsequently , the 3d semiconductor memory device of fig1 f can be implemented by performing the method that has been described above with reference to fig1 d and 13e . according to an embodiment of the inventive concept , after forming the empty regions 140 of fig1 b and before forming a gate dielectric layer , an oxidizing process may be performed in the exposed sidewall of the lower active pattern 250 . the 3d semiconductor memory devices according to embodiments of the inventive concept may be implemented as various types of packages . for example , the 3d semiconductor memory devices according to embodiments of the inventive concept may be packaged in a package type such as package on package ( pop ), ball grid arrays ( bgas ), chip scale packages ( csps ), plastic leaded chip carrier ( plcc ), plastic dual in - line package ( pdip ), die in waffle pack ( diwp ), die in wafer form ( diwf ), chip on board ( cob ), ceramic dual in - line package ( cerdip ), plastic metric quad flat pack ( mqfp ), thin quad flat pack ( tqfp ), small outline package ( sop ), shrink small outline package ( ssop ), thin small outline package ( tsop ), thin quad flat pack ( tqfp ), system in package ( sip ), multi chip package ( mcp ), wafer level stack package ( wlsp ), die in wafer form ( diwf ), die on waffle package ( dowp ), wafer - level fabricated package ( wfp ) and wafer - level processed stack package ( wsp ). a package on which the 3d semiconductor memory device according to embodiments of the inventive concept is mounted may further include at least one semiconductor device ( for example , a controller , a memory device and / or a hybrid device ) performing another function . fig1 is a block diagram schematically illustrating an example of an electronic system including a 3d semiconductor memory device according to an embodiment of the inventive concept . referring to fig1 , an electronic system 1100 according to an embodiment of the inventive concept may include a controller 1110 , an input / output ( i / o ) unit 1120 , a memory device 1130 , an interface 1140 , and a bus 1150 . the controller 1110 , the input / output ( i / o ) unit 1120 , the memory device 1130 and / or the interface 1140 may be connected through the bus 1150 . the bus 1150 corresponds to a path for transferring data . the controller 1110 may include at least one of a microprocessor , a digital signal processor , a microcontroller , and logical devices for performing a function similar to the functions of the elements . the input / output unit 1120 may include a keypad , a keyboard , a display device and others . the memory device 1130 may store data and / or commands . the memory device 1130 may include at least one of the 3d semiconductor memory devices according to embodiments of the inventive concept . also , the memory device 1130 may further include another type of semiconductor memory device ( for example , phase - change random access memory ( pram ), magnetoresistive random access memory ( mram ), dynamic random access memory ( dram ) and / or static random access memory ( sram )). the interface 1140 may transmit data to a communication network or receive data from the communication network . the interface 1140 may have a wired type or a wireless type . for example , the interface 1140 may include an antenna or a wired / wireless transceiver . although not shown , the electronic system 1100 is a working memory device for improving the function of the controller 1110 , and may further include a high - speed dram and / or a high - speed sram . the electronic system 1100 may be applied to personal digital assistants ( pdas ), portable computers , web tablets , wireless phones , mobile phones , digital music players , memory cards , and all electronic devices for transmitting / receiving information at a wireless environment . fig1 is a block diagram schematically illustrating an example of a memory card including a 3d semiconductor memory device according to an embodiment of the inventive concept . referring to fig1 , a memory card 1200 according to an embodiment of the inventive concept may include a memory device 1210 . the memory device 1210 may include at least one of the 3d semiconductor memory devices according to embodiments of the inventive concept . also , the memory device 1210 may further include another type of semiconductor memory device ( for example , pram , mram , dram and / or sram ). the memory card 1200 may include a memory controller 1220 for controlling data exchange between a host and the memory device 1210 . the memory controller 1220 may include a processing unit 1222 for controlling the overall operation of the memory card 1200 . also , the memory controller 1220 may include an sram 1221 that is used as the working memory of the processing unit 1222 . furthermore , the memory controller 1220 may further include a host interface 1223 and a memory interface 1225 . the host interface 1223 may include a data exchange protocol between the memory card 1200 and the host . the memory interface 1225 may connect the memory controller 1220 and the memory device 1210 . in addition , the memory controller 1220 may further include an error correction block ( ecc ) 1224 . the error correction block 1224 may detect and correct the error of data that is read from the memory device 1210 . although not shown , the memory card 1200 may further include a rom that stores code data for interfacing with the host . the memory card 1200 may be used as a portable data memory card . on the contrary , the memory card 1200 may be implemented as a solid state disk ( ssd ) that may replace the hard disk of a computer system . according to the above - described 3d semiconductor memory device , the vertical active pattern can be disposed in the recess region of the common source region and be connected to the well region . therefore , the distance between the vertical active pattern and the common source region can be minimized , and also , the vertical active pattern can be connected to the well region . as a result , the 3d semiconductor memory device which has excellent reliability and is optimized for high integration can be implemented . the above - disclosed subject matter is to be considered illustrative and not restrictive , and the appended claims are intended to cover all such modifications , enhancements , and other embodiments , which fall within the true spirit and scope of the inventive concept . thus , to the maximum extent allowed by law , the scope of the inventive concept is to be determined by the broadest permissible interpretation of the following claims and their equivalents , and shall not be restricted or limited by the foregoing detailed description .	7
the light wand of the present invention can be any shape or size . preferably , the wand is small enough to be carried . for example , the wand can be , but is not limited to the following dimensions : approximately 2½ inches × 7 inches × 1 inch . the light wand is shaped for ease of use . light emitting diodes ( leds ) are used to emit light energy for the promotion of tissue healing and other beneficial results . the light energy from leds can assist with various skin conditions , for example , acne , rosacea , and eczema and reduce inflammation in swollen gums associated with baby teething . monochromatic light from leds is focused light energy that isolates on the most potent frequencies for the relief of acute or chronic pain and wound healing . cell tissue responds best to certain frequencies that appear to be with the infrared spectrum , such as 660 nanometers ( nm ), 660 nm , 880 nm , 940 nm and 950 nm . the water and blood content within the body tissue restrict full absorption of light frequencies outside the range of 600 - 980 nm . one frequency of light may be a primary resonant frequency for the body , while the others may be wasted harmonics . a single wavelength within the middle of the spectrum ( e . g . 660 nm ) is the most resonant frequency to the human tissue . an application of a 660 nm light beam for several minutes to a wound approximately the size of a half of dollar every two hours can ( within a day or two ) stimulate the generation of new skin without scabbing or forming scar tissue . photons emitted by the monochromic leds are absorbed by the skin and underlying tissue , triggering biological changes within the body in a process know as “ photo - bio - stimulation .” monochromatic light increases oxygen and blood flow , wound healing and stimulates nerve functioning as well as facilitating pain reduction and muscular relaxation . light in the red spectrum and the infrared spectrum enhances and speeds up certain cellular metabolic processes , such as activity of mitochondria ( cellular organelles outside the nucleus that convert stored chemical energy into a more usable form ), charging the electrophysiological ( electrical aspect ) properties of the cell membrane and activating enzymes which turn into activate key chemical reactions . light energy is used as trigger for the rearrangement of cellular metabolism . there are photo acceptors at the molecular and cellular level that , when triggered , cause a series of biological actions . for example , dna and rna synthesis , protein and collagen synthesis and cellular proliferation are all increased when exposed to monochromatic light . the results of these biological actions are a rapid regeneration , normalization and healing of damaged cells tissue . exposure to monochromic led &# 39 ; s ( light ) energy is an effective therapy that works in harmony with the body &# 39 ; s own healing and pain relieving mechanisms . there are no known harmful side effects from the led &# 39 ; s light . light technology can also be used with hard - to - heal wounds , such as diabetic ulcers , serious burn and severe oral sores caused by chemotherapy and radiation . the light energy from monochromic leds stimulates the production of collagen , the most common protein found in the body . this essential protein is used to repair damaged tissues and replace old tissue . collagen is the substance that holds cells together and has a high degree of elasticity . by increasing collagen production , less scar tissue is formed at the site of injury . the led light energy also increases circulation by increasing the actual formation of the new capillaries , which are additional blood vessels that replace damaged ones . new capillaries that carry oxygen and nutrients are needed for healing and allow waste to be carried away for healthy skin to grow . led light energy using monochromic light also stimulates the lymphatic system , helping to eliminate toxins and excess fluids from the issue . the diameter of the lymph vessel ( a vascular duct ) accompanying lymph flow can be doubled with the use of light therapy that can increase the number of white blood cells in the blood circulation . monochromic led light therapy can also stimulate the release of adenosine triphosphate ( atp ). this chemical is the body &# 39 ; s major carrier of energy to the cells . increased amounts of this chemical allows cells to accept nutrients faster , and get rid of waste products faster by increasing the energy in the cell . increases of rna and dna synthesis also are available with light therapy that helps older or damaged cells to be replaced faster . further biological effects of led light therapy include the following . the led light can reduce excitability of the nerves tissue . the photon light energy enters the body as negative ions that require the body to send positive ions , calcium among others , to flow to the area being treated . these ions assist in regulating the nerves , thereby relieving pain . the led light can also stimulates the activity of the fibroblasts in the connective tissue . they are capable of forming collagen which aids in the repair process . led light stimulates proper tissue granulation , which is part of the healing process of inflamed tissue , such as acne breakouts . monochromic led light stimulates biological processes . just as plants are exposed to normal sunlight to synthesize carbohydrates in their chlorophyll - containing tissue ( photosynthesis ), light stimulates the formation and release of our own chemical compounds . in light therapy , the monochromic infrared light energy has a stimulating effect on the tissues because it increases cellular energy . the light energy becomes absorbed in the tissue , hence stimulating the metabolic process . the tissues exposed to monochromatic light increase blood flow , thus helping to carry vitamins and nutrients into the area where they are most needed with no damage to the surrounding tissues . as a result of increased blood flow , toxins and waste bi - products are taken away from the tissue . light therapy is also know as “ photo therapy ”. for instance , visible red light has a positive effect at a cellular level on living tissue . this type of light therapy is beneficial in treating conditions close to the surface . skin - layers because of their high blood and water content absorb red light readily . light and all electromagnetic energy travels as bundles of energy called photons . the center ( nucleus ) of the atom contains neurons and protons . the nucleus is surrounded by electrons moving in specific orbits . energy , in the form of photons , is released when the electrons change orbits . it is these bundles of energy that trigger biological changes within the body . we are constantly bombarded by photons from ordinary light sources including sunlight . monochromatic light created by the led &# 39 ; s of the present invention has the ability to control and concentrate these photons . to accomplish these benefits , the following example is given . this example is merely illustrative of the principles of the present invention and is not meant to limit the invention to embodiments given in this example . in fig1 , a top perspective view of a light wand 2 is shown . light wand 2 includes a lens cover 4 , which is used to protect the leds disposed underneath the cover . the lens cover can be clear or colored transparently , such as a blue transparent . the light wand further includes a handle 6 for gripping the wand . the wand can be any shape or design and does not necessarily require a handle to function within the scope of the present invention . the wand 2 further includes a battery cover 10 for protecting the power source disposed beneath cover 10 . preferably the power source is four aa batteries , however an ac adapter can be used and plugged into receptacle 12 . power switch 14 turns the light wand on and off . the power output for the light wand is preferably a steady power output of about 20 milliwatts to about 50 milliwatts . head 16 holds the circuitry for a control unit 22 as shown in fig2 and fig5 a and 5b . control unit 22 includes control switches 22 and 24 . in fig5 a and 5b theses switches are denoted by sw 2 , sw 3 . these control switches are for controlling the light delivery mode ( pulse or concentrated stream of light or both ), and the leds intensity level . the symbol sw 1 denotes power switch 14 . a microprocessor pic18c505c further provides control of the light mode and intensity of the leds . in fig5 b , the leds are denoted by led 1 - led 36 . in this example , there are ( 18 ) red leds and ( 18 ) red leds . it is preferred that the number of leds are even to provide a uniform distribution over the treatment site . however , it is within the scope of this invention to provide leds having a total amount that is an odd number . the distribution of the light energy will depend on the array of leds in the wand . for example , as shown in fig3 a and fig3 b , two different arrays of leds are shown . it is preferred that the led array is circular to allow uniform distribution of the light energy to the treatment site . shown in these figures are red led 30 and infrared led 32 . fig3 a illustrates a total number of leds of odd numbers ( 27 red , 25 infrared ). fig3 b illustrates a total number of leds of even numbers ( 18 red , 18 infrared ). again the even numbers are preferred to distribute uniform amounts of light energy ., both arrays are in a circular pattern to further the uniform emitting of the light energy . the leds are preferably red and / or infra red . the following illustration gives examples of the specifications of such leds . this illustration is not meant to limit the scope of the invention to this embodiment , but is merely given as an example of what leds can be used with the present invention for the advantages previously discussed . a light wand having 18 infrared and 18 red led typically provides an average light output energy density per minute of 1 . 46 joules / cm 2 . the total effective area of light out put is typically about 16 centimeters squared . again , the round shape of the led array assists in transmitting a uniform dosage of light energy to the treatment site without the need for a user to move the light wand back and forth to apply a uniform dosage of the led light energy . the light wand gives a user the ability to choose from at least 7 frequencies and at least 8 energy densities . the light frequencies are restricted to the range where body tissue can have full absorption , which is between about 600 nm to about 980 nm . preferably the frequencies are set at about 660 nm for red led and about 850 nm for infrared led . the control unit provides flexibility in led light delivery for the healing of tissue . again , cell tissue responds best to certain frequencies that appear to be with the infrared spectrum , such as 660 nanometers ( nm ), 660 nm , 880 nm , 940 nm and 950 nm . the water and blood content within the body tissue restrict full absorption of light frequencies outside the range of 600 - 980 nm . one frequency of light , a single wavelength that is preferably 660 nm is the most resonant frequency to the human tissue . an application of a 660 nm light beam for several minutes to a wound approximately the size of a half of dollar every two hours can ( within a day or two ) stimulate the generation of new skin without scabbing or forming scar tissue . fig4 illustrates a light wand having red leds only . in this illustration red leds 32 are mounted about head 4 in a circular array . the leds can have a total number that is odd or even . again , an even number of leds is preferred to assist in the uniform distribution of light energy . the energy intensity of the light wand has at least ( 8 ) settings . typical average energy light output per minute is estimated at about 1 . 3 joules / cm squared / minute . the following table illustrates and exemplary energy level settings of the present invention . this example is given for illustration purposes only and is not meant to limit the invention to this particular illustration . the above example demonstrates that the energy level settings may have a temporal relationship with the treatment time . for example , in this illustration there is an underlying constant level of light energy and the intensity is determined by the time of exposure . the exposure time is controlled by the control unit circuitry previously described above and shown in detail in fig5 a and 5b . an automatic shut off feature is included in the circuitry to avoid under and over exposure of the light energy . the automatic shut off feature is not a typical shut off circuit . through the microprocessor , the automatic shut off feature consistently provides control over the leds to emit the desired intensity and frequency of light energy . this feature prevents over or under exposure of the treatment site . light therapy from the light wand is emitted either in a pulsed or a constant light stream or beam or beams . the automatic shut off is provided in the control unit ( microprocessor circuitry ) to avoid over or under exposure of the treatment site . this automatic shut off turns the device off when the desired intensity is reached . this device is controlled by a microprocessor shown in fig5 b that prevents over and under exposure to the treatment site . the automatic shut off feature through the microprocessor adjusts the timing of exposure as the internal or external power source weakens or fluctuates . for example , with an internal battery source , as the battery weakens , the microprocessor adjusts the time of exposure so that the desired intensity of the leds is consistently achieved . if the power source is too weak to deliver the desired intensity , the device warns the user of this condition , and will prevent delivery of an undesirable dose . similarly , if the power source is too high , the control unit will decrease the time of exposure so that the desired frequency and intensity is achieved without over exposure to the treatment site . the present invention also has the ability to control time of light energy delivery and intensity of light energy delivery . the intensity of the light energy may be controlled by the control unit , in particular through sw 3 in fig5 b ( control switch 24 ) through a direct correlation in power available to the leds . for example , with this power supply method as the control switch 24 is increased , the power available to the leds is increased . this increase in power will increase the intensity of the treatment . the control unit will prevent any over or under exposure to the treatment site allowing consistent delivery of the desired joules of light energy . the description of operation includes turning on power switch 14 . either the ac adapter can be used or the battery pack located inside the light wand . the user then selects what mode to deliver . the mode refers to the type of light delivery , pulsed , constant stream of light or a combination of both . after the mode is selected , the intensity may be selected . there is no limitation in the order of using the control switches in the control unit . any sequence of steps can be used in the present invention . the user then applies the wand over the treatment site . the wand automatically shuts off after the selected treatment intensity is delivered . the automatic shut off protects the treatment site from being over exposed . an electric timer integrated in the microprocessor of the control unit prevents the treatment site from being under exposed . this feature provides consistent treatment exposure to the treatment site without the user induced error or speculation on how long to treat the treatment site . it should be understood that the above description is only representative of illustrative examples of embodiments . for the reader &# 39 ; s convenience , the above description has focused on a representative sample of all possible embodiments , a sample that teaches the principles of the invention . other embodiments may result from a different combination of portions of different embodiments . the description has not attempted to exhaustively enumerate all possible variations . furthermore , since numerous modifications and variations will readily occur to those skilled in the art , it is not desired that the present invention be limited to the exact construction and operation illustrated . accordingly , all suitable modifications and equivalents that may be resorted to are intended to fall within the scope of the claims .	0
in the following description , for the purposes of explanation , numerous specific details are set forth in order to provide a thorough understanding of exemplary embodiments . it should be apparent , however , that exemplary embodiments may be practiced without these specific details or with an equivalent arrangement . in other instances , well - known structures and devices are shown in block diagram form in order to avoid unnecessarily obscuring exemplary embodiments . in addition , unless otherwise indicated , all numbers expressing quantities , ratios , and numerical properties of ingredients , reaction conditions , and so forth used in the specification and claims are to be understood as being modified in all instances by the term “ about .” the present disclosure addresses and solves problems of high power consumption , unnecessary pre - charging , and slow read cycle times . the present disclosure addresses and solves such problems , for instance , by , inter alia , providing a fuse state of a fuse unit cell based on a discharging of capacitors within a fuse sensing circuit that is coupled to the fuse unit cell . fig2 schematically illustrates a fuse sensing circuit that indicates a fuse state of a fuse unit cell based on a discharging of capacitors of the fuse sensing circuit , in accordance with an exemplary embodiment of the present disclosure . as shown , the circuit in fig2 includes fuse unit cell 201 coupled to sensing circuit 203 . fuse unit cell 201 includes fuse 205 having one end coupled to a power source ( e . g ., fsource ) and another end coupled to program transistor 207 . for example , while program transistor 207 is activated ( e . g ., based on inputs , fu_row_pg and fu_clm_pg , to and gate 209 ), a large current from fsource may go through fuse unit cell 201 , causing fuse 205 to become blown . to detect the fuse state ( e . g ., blown , unblown , etc .) of fuse 205 , fuse unit cell 201 includes reference resistor 211 along with transistors 213 and 215 that are connected to sensing circuit 203 . sensing circuit 203 includes two capacitors 217 a and 217 b that charge and discharge based on a sense input terminal of the sensing circuit 203 ( e . g ., based on the sense and inverted sense input signals at inverters 219 and 221 , respectively ). as shown , current from a power rail charges capacitor 217 a through charge path 223 a ( e . g ., that includes resistor 225 and pass - gate 227 a ) and capacitor 217 b through charge path 223 b ( e . g ., that includes resistor 225 and pass - gate 227 b ) when their respective pass - gates 227 a and 227 b are activated ( e . g ., sense =“ 0 ”). in addition , capacitor 217 a discharges current to fuse unit cell 201 ( e . g ., at its inverted / reference bitline ( blb )) through discharge path 229 a ( e . g ., that includes pass - gate 231 a and resistor 233 a ), and capacitor 217 b discharges current to fuse unit cell 201 ( e . g ., at its bitline ( bl )) through discharge path 229 b ( e . g ., that includes pass - gate 231 b and resistor 233 b ) when their respective pass - gates 231 a and 231 b are activated ( e . g ., sense =“ 1 ”). by way of example , at sense falling edge , the two capacitors 217 a and 217 b may start to charge . at sense rising edge , the two capacitors 217 a and 217 b may stop charging , and start to discharge . in sense mode , fsource may be fixed to a ground rail , and program transistor 207 may be switched off . if , for instance , fu_row_rd is selected , transistors 213 and 215 will be switched on . thus , when pass - gates 229 a and 229 b are activated , current will discharge from capacitor 217 a to the ground rail through transistor 213 and reference resistor 211 , and from capacitor 217 b to the ground rail through transistor 215 and fuse 205 . in one scenario , the resistance of reference resistor 211 may be 1 . 4 kiloohms , the resistance of unblown fuse 205 may be 140 ohms , and the resistance of blown fuse 205 may be 5 kiloohms . as such , regardless of the state of fuse 205 ( e . g ., blown , unblown , etc . ), the discharging rates with respect to the currents from capacitors 217 a and 217 b will not be the same and , thus , there will be a timing skew between the clock input and the d input at flip - flop 235 ( e . g ., based on inputs received at inverter 237 a and 237 b ). for example , the rise of the d input will occur before the rise of the clock input when fuse 205 is unblown ( e . g ., causing dout to be “ 0 ”), and the rise of the clock input will occur before the rise of the d input when fuse 205 is blown ( e . g ., causing dout to be “ 1 ”). in this way , the fuse state of fuse unit cell 201 ( and fuse 205 ) may be ascertained regardless of whether fuse 205 is blown or unblown . in addition , compared with the traditional circuit in fig1 , the circuit in fig2 may significantly reduce power consumption as a result of decreases in the minimum sensing supply voltage and the sensing current ( e . g ., there may only be transient current at sense clock &# 39 ; s rising edge and falling edge ). furthermore , the circuit in fig2 may increase read cycle times since read frequency can be increased ( e . g ., no need for unnecessary pre - charging ), and reduce chip area requirements for sensing purposes ( e . g ., no need for additional pre - charge pins ). fig3 schematically illustrates waveform diagrams of various signals based on a fuse state , in accordance with various exemplary embodiments of the present disclosure . for example , diagrams 301 and 303 may reflect signals with respect to the circuit of fig2 , where diagram 301 depicts a scenario with fuse 205 being unblown , and diagram 303 depicts a scenario with fuse 205 being blown . in the scenario associated with diagram 301 , capacitors 217 a and 217 b may start to discharge as a result of the rising edge of the sense input , sense , at time 305 . because the resistance of unblown fuse 205 is less than the resistance of reference resistor 211 , the discharge rate of capacitor 217 a is less than the discharge rate of capacitor 217 b ( e . g ., as illustrated by signals a and b ). thus , the rise of the d input at flip - flop 235 will occur before the rise of the clock input at flip - flop 235 ( e . g ., the rise of the clock input will occur at time 307 ). consequently , the dout signal ( e . g ., the sense output signal ) will be “ 0 ,” indicating that the fuse state of fuse unit cell 201 is unblown . similarly , in the scenario associated with diagram 303 , capacitors 217 a and 217 b may start to discharge as a result of the rising edge of the sense input , sense , at time 309 . however , because the resistance of blown fuse 205 is greater than the resistance of reference resistor 211 , the rise of the clock input at flip - flop 235 will occur before the rise of the d input at flip - flop 235 ( e . g ., the rise of the clock input will occur at time 311 ). accordingly , the dout signal will be “ 1 ,” indicating that the fuse state of fuse unit cell 201 is blown . in addition , as shown in diagrams 301 and 303 , the timing skews between the d input and the clock input may vary ( e . g ., having timing skews of 125 ps and 260 ps , respectively ). nonetheless , the reliability and the accuracy of the indicated fuse state may remain unaffected by such variations ( e . g ., the indicated fuse state may be detected even when timing skews of as little as 20 ps ). therefore , as compared with the traditional circuit of fig1 , variations of process , voltage , temperature , etc ., may not have as much effect on embodiments of the present disclosure . the embodiments of the present disclosure can achieve several technical effects , including power consumption efficiency , smaller device sizes , and faster read cycle times . embodiments of the present disclosure enjoy utility in various industrial applications as , for example , microprocessors , smart phones , mobile phones , cellular handsets , set - top boxes , dvd recorders and players , automotive navigation , printers and peripherals , networking and telecom equipment , gaming systems , digital cameras , or any other devices utilizing logic or high - voltage technology nodes . the present disclosure therefore enjoys industrial applicability in any of various types of highly integrated semiconductor devices . in the preceding description , the present disclosure is described with reference to specifically exemplary embodiments thereof . it will , however , be evident that various modifications and changes may be made thereto without departing from the broader spirit and scope of the present disclosure , as set forth in the claims . the specification and drawings are , accordingly , to be regarded as illustrative and not as restrictive . it is understood that the present disclosure is capable of using various other combinations and embodiments and is capable of any changes or modifications within the scope of the inventive concept as expressed herein .	7
generally , the present invention provides the ability to seal chip / structures / wafers which enables mechanical stability of critical joined components and protects from outside environmental damage . the sealing procedure of the present invention for sealing stacked wafer or chips enables structures to be hermetically sealed at a chip / die level and also allows wafer - level sealing which will enable downstream full - wafer processing . furthermore , the sealing solution can also be utilized for electrical signal propagation and thermal dissipation or as a thermal conductor ( through sealant material itself or using sealant as a thermal structure for dissipation ). materials that can be used to seal together chips or wafers include : metals ( for example : cu — cu , au — au , etc . ); alloys ( such as : cu — sn , ausn , etc . ); solders ; dielectrics ( oxide - oxide ); conductive adhesives ( cu - loaded pastes ) and any combination thereof ( example indium - oxide ). more specifically , referring to fig1 a , for illustrative purposes , two silicon wafers 10 are shown . a first silicon wafer 10 a is positioned over a second silicon wafer 10 b . each silicon wafer may include a plurality of electrical elements fabricated using known semiconductor fabricating techniques on a top surface and / or in an upper layer of the wafer or a chip . further , the electrical elements can be connected to each other and to electrically conductive vias extending throughout the wafer or chip and / or a substrate portion of the wafer or chip forming multiple circuits to provide , for example , power , connectivity , or circuit logic . the first silicon wafer 10 a includes a silicon layer 14 a and an oxide layer 18 a . similarly , the second silicon wafer 10 b includes a silicon layer 14 b and an oxide layer 18 b , in mirror image relationship to the first silicon wafer 10 a . further , the first silicon wafer 10 a includes a copper ( cu ) plated bond pad 22 a , and the second silicon wafer 10 b also includes a copper ( cu ) plated bond pad 22 b . the bond pads 22 a and 22 b are positioned in mating relationship to each other . referring to fig1 b , the first silicon wafer 10 a and second silicon wafer 10 b are bonded together at a bonded area 26 using the copper plated bond pads 22 a , 22 b of silicon layers 14 a , 14 b . the bonded area 26 formed by compressing the first and second silicon wafer 10 , 10 b together . heat is also applied to the bonded area 26 to form the bond and seal the wafers 10 a , 10 b together . thus , the first and second silicon wafers 10 a , 10 b are positioned in mating relation , as shown in fig1 a , and the cu plated bonding pads 22 a , 22 b are mated together and sealed by using compression and heat . the bonded structure is preferably hermetically sealed , i . e ., an airtight seal , which is intended to secure against the entry of unwanted particles and elements to maintain the quality of the electrical components and circuitry in the bonded structure . other material may be used other than cooper to accomplish the sealing bond . further , the seal prevents corrosion from atmosphere ( humidity or temperature ) or foreign materials ( contamination ) and wet chemistry reaction and plasma damage from beol / packaging processes . referring to fig2 , a silicon wafer 100 is shown having a plurality of integrated circuits ( ics or chips ) 104 positioned on a planar surface area 102 of the wafer 100 . each of the chips 104 includes a bonding material 108 forming a perimeter on a planar surface area 105 of the chip 104 . the wafer 102 also has bonding material 112 forming a perimeter on the planar surface area 102 . in the embodiment of the invention shown in fig2 , the bonding material is copper , however , other suitable electrically conductive or non - conductive materials may be used . it is understood , that the chip and wafer perimeters formed by the bonding materials 108 , 112 , respectively , may begin from outer edges 106 , 101 , respectively , and extend radially inwardly from the outer edges along the planar surface areas 105 , 102 , respectively , of the chips 104 and the wafer 100 . further , the chip and wafers perimeters formed by the bonding materials 108 , 112 can also be adjacent , offset , or in spaced adjacency from the outer edges 106 , 101 , respectively . the chips 104 also include dummy bonding pads ( pads , support columns / pillars ) 116 ( shown in fig2 ), which may be made of copper or other suitable materials . the pads or copper pad ( support columns / pillars ) 116 are structures without any electrical connection , but have a specified position on the planar surface area 105 of the chip 104 and a specified height to contact mating pads on a chip ( not shown ) to be fitted over the chip 104 shown in fig2 . the mating pads then form a structural column or support column ( or pillar ) in a sealed bonded structure of wafers or separate chips . the mating pads can also be bonded together when the wafer of chip is mated , thus forming a bonded support column . the mating pads 116 help support the wafer when stacked with other wafers , as will be discussed herein referring to fig3 c . referring to fig3 a and 3b , a pair of chips 200 are shown in mirror image relation . a first chip 200 a and second chip 200 b each have planar surface areas 204 a , 204 b , respectively . bonding materials 206 a , 206 b , respectively , define perimeters around the surface areas 204 a , 204 b , respectively , on the first and second chips 200 a , 200 b . as discussed in relation to fig2 , the bonding material may be cooper , as well , as other suitable materials . the perimeters defined by the bonding materials 206 a , 206 b extend inwardly along the planar surface areas 204 a , 204 b , respectively , from outer edges 202 a , 202 b , respectively . the chips 200 a , 200 b also include dummy bonding pads 208 a , 208 b , respectively ( similarly to the chips 104 shown in fig2 ), which may be made of copper or other suitable materials as discussed in regard to pads 116 on chip 104 in fig2 . similarly to chip 104 shown in fig2 , the pads 208 a , 208 b shown in fig3 a , 3 b are structures without any electrical connection , but have a specified position on the planar surface areas 204 a , 204 b of the chips 200 a , 200 b , respectively . the bonding pads 212 a , 212 b may be placed in a geometric pattern , as shown in fig3 a and 3b , but also may be placed in any pattern , or non - pattern desired , or in any quantity desired . each of the pads 208 a on chip 200 a have a specified height to contact mating pads 208 b on chip 200 b when the chips 200 a , 200 b are placed in overlapping relation and bonded as shown in fig3 c . the pads 208 a , 208 b coupled ( or bonded or fused ) together form mated pads 220 or structural columns , show in fig3 c , in the bonded chip structure 250 , as shown in fig3 c . further , the bonded chip structure 250 comprises a bonded perimeter 216 consisting of bonding material 206 a and bonding material 206 b mated together . in the bonded chip 250 ( shown in fig3 c ), the bonding material 206 a , 206 b shown in fig3 a and 3b are affixed together to form a seal 216 around the perimeter of the bonded chip 250 . the forming of the seal 216 includes compressing the bonding material together and heating the bonding material . other methods of forming the seal are also contemplated and within the scope of the present invention . the seal 216 stops unwanted entry of , for example , materials , substances , or debris into the bonded chip 250 , i . e ., between the chips 300 a and 300 b . referring to fig3 c , the wafers 200 a , 200 b are shown bonded together as a bonded chip structure 250 , in cross - section , so that the mated pads or structural columns 220 are shown . the mated pads or structural columns 220 are the pads ( or dummy pads ) 212 a on first wafer 200 a and second wafer 200 b mated together . the dummy pads mated together to form structural columns 220 provide strength to the bonded wafer 250 . the pads 220 help support the surface areas 204 a and 204 b of the first and second wafers 200 a , 200 b , respectively . the surface areas 204 a , 204 b have an inherent weight , and thus there are axial forces 252 across the surface areas 204 a , 204 b perpendicular to the “ x ” axis 253 a and along the “ y ” axis 253 b . more particularly , the axial forces 252 are from , for example , the inherent weight of the surface areas 204 a , 204 b of the first and second wafers 200 a , 200 b due to gravitation forces , or axial force ( or pressure ) from the weight of other chips ( or wafers ) stacked on the bonded chip 250 . the structural columns 220 provide support along the surface areas 204 a , 204 b of the first and second chips 200 a , 200 b , respectively , to support the axial forces . more specifically , when additional chips are stacked over each other , additional axial forces from the weight of additional chips bear down ( along the “ y ” axis 253 b ) on the outer top surface 256 of the bonded wafer 250 . further , the mated pads / structural columns 220 help to stabilize the bonded wafer 250 against torsional forces ( or stresses ), which may occur in the processing or fabricating of the wafer or from disproportionate weight distribution from stacking other chips ( or wafers ) over one another such that twisting or bending occurs along the surface areas 204 a , 204 b of the chips 200 a , 200 b . if torsional stresses are applied to the bonded chip 250 , the torsion causes twisting of the bonded chip 250 that may result in shearing stress which are perpendicular to surface areas 204 a , 204 b ( in the “ y ” direction 253 b ). thus , in one example , the structural columns may be positioned on the surface area of a chip or wafer in an area unpopulated by other components to effectively distribute axial and torsional forces throughout the chip or wafer during processing . distribution of forces throughout the chip or wafer lessens the force in one particular area and thereby reduces the stress in that area lessening the likelihood of a stress related fracture or break in the chip or wafer structure . also , the support columns reduce possible stresses from torsion and axial loads on the seal . further , an uncompromised seal ( preferably a hermetic seal ) about each chip or wafer prevents , for example , liquid and gas etchants / corrosives and particulate materials from ingressing into areas which will be damaged by such ingress . it is understood that a chip or wafer may have multiple electrical reference layers connected by vertical vias ( not shown ). the dummy pads , for example , as described in relation to fig3 a - 3c , can be positioned between layers in the chip or wafer to provide support between the layers , as well as providing support between the chips or wafers themselves . referring to fig4 a and 4b , wafers 300 a , 300 b , respectively , include a plurality of chips 304 positioned on surface areas 302 a , 302 b . the surface areas of the wafers 300 a , 300 b include bonding material 312 forming a perimeter around the wafers 300 a , 300 b with a thickness 320 ( shown in fig4 d ) starting from the edge of the wafers 301 a , 301 b and extending inwardly on the surface areas 302 a , 302 b of the wafers 300 a , 300 b . the chips 304 on the surface areas 302 a , 302 b of the wafers 300 a , 300 b include dummy pads 208 a , 208 b as depicted in more detail in fig3 a and 3b , and described above . further , the chips 304 on wafers 300 a , 300 b include bonding material 206 a , 206 b , respectively , defining a perimeter around the chip 304 as shown in more detail in fig3 a and 3b , and described above . wafers 300 a and 300 b are combined by positioning one wafer over the other to form bonded wafer 350 , shown in fig4 c . in the bonded wafer 350 , the bonding material 312 shown in fig4 a and 4b are affixed together to form a seal 312 around the perimeter of the bonded wafer 350 . the forming of the seal includes compressing the bonding material 312 between the wafers 300 a , 300 b and heating the bonding material 312 to form the bonded seal 316 . the bonded seal 316 stops unwanted entry of , for example , materials , substances , or debris into the bonded wafer 350 , i . e ., between the wafers 300 a and 300 b . referring to fig4 d , a cross - section of the combined wafers 350 is shown along line x - x to show the bonded seal 316 , resulting from bonding together of bonding material 312 on each wafer 300 a , 300 b , extending inwardly from the edges 301 a and 301 b of the wafers 300 a , 300 b . the bonded seal 316 around the perimeter of the wafer 350 is shown in fig4 d . while the present invention has been particularly shown and described with respect to preferred embodiments thereof , it will be understood by those skilled in the art that changes in forms and details may be made without departing from the spirit and scope of the present application . it is therefore intended that the present invention not be limited to the exact forms and details described and illustrated herein , but falls within the scope of the appended claims .	7
referring to fig1 - 3 of the drawings , a welding assembly 10 can be seen having a mounting base 11 and a back plate 12 , shown in broken lines . a support carriage 13 is movably positioned on the block plate by multiple linear bearing assemblies 14 on respective bearing races 15 . the welding assembly has a power welder 16 secured within the support carriage 13 . the power welder 16 has a servo motor 17 , connected to a gear reducer 18 by a motor adapter 19 . the gear reducer 18 has a spindle assembly 20 with an attached driver 21 , best seen in fig1 and 2 of the drawings which will be discussed in greater detail hereinafter . the carriage 13 is movable in a vertical plane by a piston and cylinder assembly 22 secured to the back plate 12 . a piston rod 23 extends from the piston and cylinder assembly 22 and is secured to the movable carriage assembly as will be well understood by those skilled in the art . the servo motor 17 is of a three phase electrical servo positioning motor , the type manufactured by emerson under model no . dxm6200 having the ability to accelerate from a forced stop position to maximum r . p . m . in a fraction of a second and to de - accelerate to the force stop position just as rapidly . such servo motors 17 are characterized by their ability to constantly start and spin and stop within six arc seconds of a predetermined position which is critical to the method of the invention and weld characteristics of the thermoplastic parts disclosed herein . the output of the servo motor 17 is connected to the gear reducer 18 by the adapter 19 that mechanically interconnects therebetween . the gear reducer 18 is commercially available at model ato14 - 003 which is a 3 to 1 gear reduction manufactured by micron instrument corporation using multiple planet gears revolving around a single true &# 34 ; sun &# 34 ; gear well known to those skilled in the art . referring now to fig3 of the drawings , the driver 21 can be seen having a parts engagement fixture 24 secured thereto . the fixture 24 is simplified for illustration purposes and would be of a custom design for each part configuration to be joined as is typical in the art . a fixed base part fixture 25 is illustrated with pre - positioned thermoplastic parts 26 and 27 therein to be joined together . the parts 26 and 27 have abutting joining surfaces . in use , the power welder assembly 10 defines a unique welding method that first positions and holds the thermoplastic parts 26 and 27 together , then applies sufficient pressure to build up substantial energy in the process before the spindle 20 and associated driver 21 and fixture 24 actually turns . the position of the movable carriages 13 is physically controlled by the piston and cylinder assembly 22 in combination with carriage positioning sensors 28 and input control activation commands from a pre - programmed c . p . u . ( central processing unit ) interconnected to the power welder assembly 16 . torque is applied to the thermoplastic parts by the output of the servo motor 17 responding to the input control activation commands from the c . p . u . in accordance with its pre - programmed instructions in combination with input from the positioning sensor 29 within the driver 21 . referring now to fig5 of the drawings , a time line activation graph 30 is illustrated that indicates a typical activation time for the servo motor 17 to effect a power weld between the thermoplastic parts 26 and 27 as hereinbefore described . the graph 30 has time lines 31 and 32 in micro - seconds and second respectively with acceleration ( a ) indicated at 33 , and de - acceleration ( da ) illustrated at 34 ( in milliseconds ) and hold time ( h ) illustrated at 35 ( in seconds ) before joined parts are released . the critical element of thermoplastic welding is to achieve a weld temperature between the parts as rapidly as possible , illustrated by the acceleration bar 33 and the de - accelerate before the formed weld joint begins to set up ( cools ) that occurs as the parts de - accelerate illustrated by the de - acceleration bar 34 . the precise controlling of the acceleration and de - acceleration of the motor 17 is achieved by the hereinbefore described ability of the servo motor 17 that is controlled by the pre - programmed c . p . u . with feedback from positioning sensor 29 achieving &# 34 ; stop &# 34 ; position of the driver 21 and fixture 24 in a consistent and repeatable fashion . the resulting weld between the joined parts is characterized by high consistence with little or no flashing thereabout . referring now to fig4 of the drawings , a comparison graph of effective rotational duration of prior art spin welding to the method of the invention is illustrated . graphic arrows 36 illustrate the typical ( minimum ) rotational revolution required by prior art spin welding that is currently possible at three - quarter of a revolution to achieve welding . the graph arrow 37 illustrates the method of the invention where an efficient superior welding can be achieved in as little as one - third of a rotation . the rotational difference ( rotational time rt ) of less than half illustrated is demonstrative of other time rotational differences achieved in more than a full rotation in which the method of the invention will always achieve a reduced rotational difference and correspondingly reduced weld time ( t ) to achieve a superior quality weld , thus duration of weld cycle is reduced and production is increased . it will be apparent to those skilled in the art that various changes and modifications may be made therein without departing from the spirit of the invention .	1
hereinafter , embodiments of the bump forming method and apparatus according to the present invention will be explained with reference to the drawings . [ 0036 ] fig1 is a plan view for showing a bump ball arranging and compression - bonding system for implementing the bump ( ball ) forming method as an embodiment of the present invention . in the figure , reference numeral 1 indicates a cassette platform , reference numeral 2 indicates a transfer robot , reference numeral 3 indicates a positioning table , reference numeral 4 indicates a cross arm , reference numeral 5 indicates an alignment unit , reference numeral 6 indicates a bonding head ( i . e ., a bump forming apparatus ), and reference numeral 7 indicates a control panel for controlling the above elements . the cassette platform 1 is a dedicated platform for setting a wafer cassette in which a plurality of silicon wafers ( i . e ., semiconductor substrates , where the silicon wafer may be simply called the wafer , hereinbelow ) are contained . the transfer robot 2 has a mechanism for extracting each wafer from the wafer cassette set on the cassette platform 1 in turn , inverting the position of the wafer by 180 ° in the vertical direction , and then setting this inverted wafer at a specific position on the positioning table 3 . the positioning table 3 is provided for defining the direction of an orientation flat or a notch of the wafer and for determining the position of the wafer to be held . the cross arm 4 has a rotation shaft 11 which is vertically positioned , four arms 12 a to 12 d horizontally and radially extending from the rotation shaft 11 , and wafer holding pads 13 a to 13 d , respectively attached to the heads of the arms 12 a to 12 d , each pad having an adjustment mechanism for attracting and holding a wafer and moving the wafer in the θ direction ( i . e ., the direction of the angle of rotation ) and in the z direction ( i . e ., the vertical direction ). the wafers , respectively held by the wafer holding pads 13 a to 13 d , are transferred by clockwise rotating the arms 12 a to 12 d around the rotation shaft 11 . the wafer holding pads 13 a to 13 d also function as a pressing device for compressing bump balls 22 ( explained below ) via a wafer . the alignment unit 5 is provided for performing alignment ( relating to parallelability and position ) of the wafer 17 transferred from the positioning table 3 by using the cross arm 4 . as shown in fig2 the bonding head 6 is a bump forming apparatus for forming bumps on pads provided at predetermined positions on a surface ( i . e ., a main surface ) of a wafer . the bonding head 6 has a double - plate structure consisting of a heater plate 21 ( i . e ., a heating device ) and a bump ball arrangement plate 23 ( i . e ., a positioning member ) for arranging bump balls 22 ( i . e ., bump materials ). the bonding head 6 also includes an ionizer 24 ( i . e ., an electrostatic charge dissipating device ), an ultrasonic generator 25 ( i . e ., an ultrasonic oscillating device ), and an air blower 26 ( i . e ., a bump ball arranging device ). the main body of the heater plate 21 is a flat plate 31 ( i . e ., a plate body ) made of , for example , ( i ) metal such as titanium ( ti ) or stainless steel , which has high heat resistance , or alloy of such metal , ( ii ) semiconductor material such as silicon ( si ), or ( iii ) ceramics such as silicon carbide ( sic ) or aluminum nitride ( aln ). the top face 31 a ( i . e ., a main surface ) of the plate 31 is polished so as to function as a heating surface for heating the bump balls 22 . in addition , a temperature sensor for measuring the temperature of the top face 31 a and a heater ( i . e ., a heating source ) are provided in the heater plate 21 , where this heater is controlled by using the control panel 7 . at each of the four corners of this plate 31 , a through hole 32 for inserting a movable shaft 35 ( explained below ) is formed in the vertical direction , where the diameter of the through hole 32 is slightly larger than that of the movable shaft 35 . the bump ball arrangement plate 23 is arranged above the heater plate 21 and in parallel to the heater plate 21 . the main body of the bump ball arrangement plate 23 is a flat plate 33 ( i . e ., a plate body ) which has substantially the same shape of the above - explained plate 31 and which is also made of , for example , ( i ) metal such as titanium ( ti ) or stainless steel , which has high heat resistance , or alloy of such metal , ( ii ) semiconductor material such as silicon ( si ), or ( iii ) ceramics such as silicon carbide ( sic ) or aluminum nitride ( aln ). the top face 33 a ( as a main surface ) of the plate 33 is polished , and holes 34 for positioning the bump balls 22 are formed at predetermined positions on the top face 33 a ( in fig2 only one hole 34 is shown ). the thickness of the plate 33 is less than the maximum diameter of the bump balls 22 , and the diameter of each hole 34 is slightly larger than the maximum diameter of the bump balls 22 . for example , when the maximum diameter of the bump balls 22 is 50 μm , the thickness of the plate 33 is 25 to 30 μm , and the diameter of the hole 34 is 55 μm . at each of the four corners of the plate 33 , the head of the movable shaft 35 is fastened by using a fastening member such as a bolt 36 . the space between the bottom face 33 b of the plate 33 and the top face 31 a of the plate 31 can be adjusted by moving the movable shaft 35 in the vertical direction . more specifically , a specific space such as 15 to 25 μm can be secured . the plate 33 also has a pull mechanism ( not shown ) for pulling the plate 33 from every corner and holding the plate so as to prevent the plate 33 from warping when the bump balls 22 are disposed on the plate 33 . in another method for preventing a warp of the plate 33 , the bump balls may be supplied little by little , that is , continuously or intermittently . the ionizer 24 is a device for dissipating electrostatic charge produced around the bump balls 22 , so as to prevent a small number of supplied bump balls from being attracted to each other due to electrostatic charge produced by the contact between the supplied bump balls . the ultrasonic generator 25 is used for generating ultrasonic waves at a contact surface between each bump ball 22 and the corresponding pad 37 on the wafer when the bump ball 22 is compression - bonded on the pad 37 . according to the generated ultrasonic waves , a resonant state is produced in the vicinity of the contact surface , thereby improving the contact strength between the bump ball 22 and the pad 37 . the air blower 26 is used for inserting bump balls 22 , supplied onto the top face 33 a of the plate 33 , into all the positioning holes 34 and collecting extra bump balls 22 which have not inserted into the holes 34 . these operations are performed by moving the shaft 27 of the air blower 26 in a direction above the top face 33 a of the plate 33 ( see the arrows in fig2 ). here , a dedicated brush or the like may be used instead of the air blower 26 , so as to insert the bump balls 22 into all the positioning holes 34 . below , the bump ball forming method as an embodiment of the present invention will be explained with reference to fig1 to 5 . first , a wafer cassette , in which wafers are contained , is set on the cassette platform 1 . in the next step , a wafer is extracted from the cassette stage by using the transfer robot 2 , which inverts the wafer by 180 ° in the vertical direction and transfers the inverted wafer onto the positioning table 3 , so as to set the wafer at a predetermined position on the positioning table 3 . on the positioning table 3 , the direction of an orientation flat or a notch of the wafer is defined , and the position of the wafer to be held is determined . each wafer , whose direction of an orientation flat or a notch has been defined , is held by the wafer holding pads 13 a to 13 d of the cross arm 4 in turn . the cross arm 4 can efficiently transfer the wafers by clockwise rotating the arms 12 a to 12 d around the rotation shaft 11 . for example , the wafer held by the wafer holding pad 13 a is transferred and set to the alignment unit 5 by clockwise rotating the arm 12 a around the rotation shaft 11 . the alignment unit 5 performs alignment ( relating to parallelability and position ) of the wafer . during the alignment , bump balls 22 are arranged at the bonding head 6 , so that the bump balls 22 are in a stand - by state . the method of arranging the bump balls 22 will be explained below . first , as shown in fig2 the bump ball arrangement plate 23 is moved upward by moving upward the movable shafts 35 attached at the four corners of the plate 33 , so that the space between the bottom face 33 b of the plate 33 and the top face 31 a of the plate 31 is set to a predetermined value , for example , 15 to 25 μm . in the next step , the bump balls 22 are supplied onto the bump ball arrangement plate 23 . here , in order to prevent the bump balls 22 from being attracted to each other by electrostatic charge , the electrostatic charge produced around the bump balls 22 is dissipated in advance by using the ionizer 24 . next , the shaft 27 of the air blower 26 ( or a dedicated brush or the like ) is moved along a direction ( see the arrows in fig2 ) above the top face 33 a of the plate 33 , so that the bump balls 22 , from which electrostatic charge has been dissipated , are inserted into all the positioning holes 34 , and simultaneously , extra bump balls 22 on the plate 33 are collected at the edge of the plate 33 . in the next step , the movable shafts 35 are moved downward so as to move the bump ball arrangement plate 23 downward , thereby making the bottom face 33 b of the plate 33 contact the top face 31 a of the plate 31 . accordingly , an upper end portion ( as a face to be compressed and bonded ) of each bump ball 22 , inserted in the positioning hole 34 , protrudes from the upper end of the hole 34 ( see fig3 ). in the following step , as shown in fig4 the cross arm 4 is operated so as to attract a wafer , for which the alignment ( relating to parallelability and position ) has been completed , by the wafer holding pad 13 a . the attracted wafer 17 is moved to the origin ( i . e ., defined as the home position ) above the top face 33 a of the plate 33 and is then lowered so as to make each bonding pad 37 , which is attached to the bottom face 17 a of the wafer 17 , contact the upper end of the corresponding bump ball 22 . in the next step , as shown in fig5 the plate 31 is heated to , for example , 150 to 250 ° c . by using the built - in heater while the wafer 17 is pressed with a predetermined pressure by the wafer holding pad 13 a . accordingly , each bump ball 22 is softened and simultaneously pressed and deformed so that the bump ball 22 is transformed into a bump 38 which has a specific shape matching the shape of the corresponding hole 34 . accordingly , bumps 38 are compression - bonded onto the bonding pads 37 provided on the bottom face 17 a of the wafer 17 by a single compressing and heating operation . when ultrasonic waves are generated at a contact face between each bump ball 22 and the bonding pad 37 by using the ultrasonic generator 25 in the compressing and heating operation , a resonant state can be produced in the vicinity of the contact face , thereby improving the contact strength between the bump ball 22 and the bonding pad 37 . the wafer 17 , on which the bumps 38 are bonded , is returned to the origin position by raising the wafer holding pad 13 a and is then transferred to the positioning table 3 by rotating the cross arm 4 . the wafer holding pad 13 a is then lowered so that the wafer 17 is put on the positioning table 3 . the wafer 17 is held by the transfer robot 2 again . this wafer 17 is inverted by 180 ° in the vertical direction and is then stored into the wafer cassette set on the cassette platform 1 . as explained in detail above , according to the bump ball forming method of the present embodiment , the bump balls 22 , from which electrostatic charge has been dissipated , are inserted into the positioning holes 34 on the bump ball arrangement plate 23 . therefore , in comparison with the conventional case of attracting bump balls , holding and positioning of the bump balls can be more easily performed . in addition , the plate 31 is heated to a predetermined temperature by using a built - in heater while the wafer 17 is pressed with a predetermined pressure by using the wafer holding pad 13 a , so that each bump ball 22 is softened and simultaneously pressed and deformed and that the bump ball 22 is transformed into a bump 38 having a specific shape . therefore , the bumps 38 , each having a specific shape , can be formed by a single compressing and heating operation ; thus , no bump ball 22 has an abnormal shape which requires an operation for correcting the shape . accordingly , it is possible to reduce the time for performing the bump forming process and also reduce the manufacturing cost . according to the bump ball arranging and compression - bonding system in the present embodiment , the bonding head 6 has a double - plate structure consisting of the heater plate 21 and the bump ball arrangement plate 23 for arranging the bump balls 22 . therefore , the holding and positioning operation of the bump balls can be easily performed , thereby reducing the time necessary for the bump forming process and also reducing the manufacturing cost . in addition , the ionizer 24 is provided . therefore , when the bump balls 22 are supplied onto the bump ball arrangement plate 23 , electrostatic charge produced by the contact between the bump balls 22 can be dissipated . accordingly , it is possible to prevent the bump balls from being attracted to each other . additionally , the ultrasonic generator 25 is provided . therefore , ultrasonic waves can be generated at a contact face between each bump ball 22 and the bonding pad 37 , thereby producing a resonant state in the vicinity of the contact face and improving the contact strength between the bump ball 22 and the bonding pad 37 . furthermore , in another method of securing a predetermined space between the bump ball arrangement plate 23 and the heater plate 21 , the bump ball arrangement plate 23 has a first magnetic material and the heater plate 21 has a second magnetic material , so that a predetermined space is secured between the bump ball arrangement plate 23 and the heater plate 21 which face each other , according to repulsive force produced by the first and second magnetic materials .	7
[ 0023 ] fig1 a to 1 c are three perspective views 10 a , 10 b and 10 c , respectively , of a portion of a telescoping tip electrode catheter 11 with a steerable portion 14 of the main catheter body 16 just proximal of the telescoping tip portion 18 according to an embodiment of the present invention . more particularly , fig1 a shows the catheter 12 including a main body portion 16 and a telescoping tip portion 18 . the telescoping tip portion of this fig1 a also shows the tip electrode 20 . fig1 b shows the steerable portion 14 of the main catheter body 16 just proximal of the telescoping tip portion 18 . the portion 18 includes a partially extended mandrel 22 which extends from and retracts to the main catheter body 16 and to which the telescoping tip electrode 20 attaches . fig1 c shows the steerable portion 14 engaged in a curve with a greater degree of curvature than the catheter portion 10 b and the mandrel 22 extended to a greater length than the mandrel 22 in the catheter portion 10 b . in alternative embodiments of the present invention , the tip electrode 22 can be retracted inside the catheter main body 16 rather than being external to the catheter main body 16 when the mandrel 22 is retracted to its full extent . [ 0024 ] fig2 is a side view of the handle portion 30 and the distal portion of the catheter main body 16 including the telescoping tip electrode 20 and the steerable portion 14 of the catheter main body 16 according to the fig1 a to 1 c embodiments . the handle portion 30 includes a slider mechanism 32 which operates the telescoping tip 18 . the mechanism 32 moves in increments along the longitudinal axis of the catheter 10 and is connected in the interior ( not shown ) of the catheter 10 to the mandrel 22 for the telescoping tip 20 . movement of the slider mechanism 32 in either direction similarly causes the mandrel 22 to move in the same direction in order to extend or retract the tip electrode 20 . for example , movement of the slider mechanism 32 proximally causes the mandrel 22 and the tip electrode 20 to retract and movement of the slider mechanism 32 distally causes the mandrel 22 and the tip electrode 20 to extend . the mechanism 32 can also be manipulated to cause partial movement of the mandrel 22 and tip electrode 20 so that partial extension at varying lengths of the tip electrode 20 can be achieved . a slider mechanism which can be used for an embodiment of the present invention is also disclosed in u . s . pat . no . 6 , 178 , 354 , to charles gibson arid issued on jan . 23 , 2001 , which is incorporated herein in its entirety by reference . the handle portion 30 also includes a thumbwheel 34 which operates the steerable portion 14 of the catheter main body . the thumbwheel 34 and operation of the steerable portion 14 is described in u . s . pat . no . 5 , 611 , 777 , to bowden et al . and issued on mar . 18 , 1997 , which is incorporated herein in its entirety by reference . the handle portion 30 also connects to a generator device 36 which is proximal of the portion 30 . the generator device portion 36 is used in a conventional manner to connect to a wire which carries power to the tip electrode 20 . such device 36 and operation is well known to those of ordinary skill in the art and therefore will not be further described herein . [ 0025 ] fig3 is an exploded perspective view of the telescoping tip electrode 20 according to the fig1 a to 1 c embodiments . in this embodiment , a bipolar electrode 20 is used , including three interlocking portions 38 , 40 and 42 . portions 38 and 42 provide an elliptical shape to the electrode 20 and are the conducting portions . portion 40 can be an electrical insulation . exemplary materials for the construction of the electrode 2 are platinum , platinum / iridium or gold , etc . an exemplary size of the electrode 20 is 9 french with a length which can vary between about 4 to 8 mm . in alternative embodiments , the electrode 20 size can be smaller than the outer diameter of the main catheter body 16 so that the electrode 20 can retract inside the catheter 10 . in further alternative embodiments , the electrode 20 can be a split electrode or any other type of shape ( e . g ., square , rectangular or circular ) electrode 20 operable to treat tissue in a cardiac or arterial passageway . [ 0026 ] fig4 is a first partial cross sectional view of the telescoping tip electrode 20 according to the fig1 a to 1 c embodiments . the electrode 20 includes conductors 44 and 46 which provide power to the portions 38 and 42 . conductors 44 and 46 extend through the mandrel 22 to the generator device 36 ( shown in fig2 ). also shown is a soldering bonding junction 48 between the electrode 20 and the mandrel 22 . [ 0027 ] fig5 is a second partial cross sectional view of the telescoping tip electrode 22 according to the fig1 a to 1 c embodiments . shown are a temperature sensor 50 and circumferential grove 52 around the electrode 20 for sensor placement . the soldering junction 48 is also shown between the electrode 20 and the mandrel 22 . referring also to fig1 c and 2 , an exemplary material for the mandrel 22 is nitinol , mp35n and sst . in alternative embodiments , where the mandrel 22 is not the electrical conductor , the material choices can be expanded to include non - conductive plastics that are durable but flexible , such as polyimide , peek or nylon , etc . in one embodiment , the length of the mandrel 22 and telescoping tip 20 portion 18 which extends or retracts from the main catheter body 16 can range in length from greater than 0 cm to about 6 cm or more in length . the diameter of the mandrel 22 can be 7 french for example . in alternative embodiments , the mandrel 22 diameter can be just smaller than the inner diameter of the main catheter body 16 shaft . [ 0028 ] fig6 is a side view of the telescoping tip portion 18 including the mandrel 22 on which the telescoping tip electrode 20 is mounted ( not shown ) and the portion of the catheter main body 16 just proximal of the telescoping tip portion 18 according to the fig1 a to 1 c embodiments . the portion of the main catheter body 16 includes a bonding area 60 in which the mechanisms to add in the steerability of the catheter 10 reside . also shown in this embodiment is a ring electrode 62 for use in bipolar recordings , as is conventional . fig7 is a partial cross section of the proximal portion of the main catheter body 16 according to the fig1 a to 1 c embodiments which shows the bonding area 60 in more detail . more particularly , the area 60 includes a steering anchor 64 and a threaded core assembly 66 for use in controlling the steerable portion 14 of the main catheter body 16 . [ 0029 ] fig8 is a partial cross section of the telescoping tip electrode catheter 10 showing the steering cables 70 and 72 for the steerable catheter portion 14 . in this embodiment , the steerable portion 14 is located proximal of the distal end of the main catheter body 16 . however , in alternative embodiments , the steerable portion 14 can extend to the distal end of the catheter main body 16 . curve directional arrows 74 show the potential direction of curvature for the steerable portion 14 in this embodiment . also shown is mandrel 22 extending through the main catheter body 16 to connect to the slider mechanism 32 , as described in u . s . pat . no . 6 , 178 , 354 , as cited above . [ 0030 ] fig9 is a partial cross section of the telescoping tip electrode catheter 10 showing the steering cables 70 and 72 and the steerable catheter portion 14 engaged in a curve 76 according to the fig1 a to 1 c embodiments . [ 0031 ] fig1 is a perspective view of the telescoping tip electrode catheter 10 with the steerable portion 14 engaged in a curve and the telescoping tip 20 being extended and contacting a treatment site 78 according to the fig1 a to 1 c embodiments . as a result of the curvature in the steerable portion 14 , additional pressure is applied to the electrode 20 to improve the contact between the electrode 20 and the treatment site 78 .	0
reference will now be made in detail to the preferred embodiments of the present invention , examples of which are illustrated in the accompanying drawings . fig5 a is a plan view of an exemplary laser head according to the present invention , and fig5 b is a plan view showing an exemplary laser pixel of the laser head of fig5 a according to the present invention . in fig5 a and 5b , a laser head 160 may have about 224 laser pixels 162 arranged along a line , wherein each of the laser pixels 162 may have a length l of about 5 μm to about 20 μm and a width w of about 3 μm to 5 μm . of course , the laser pixel 162 may have a different size , i . e ., larger or smaller , than the laser pixels 162 when the power of each of the laser pixels 162 is considered . for example , an entire size of the laser pixels 162 within the laser head 160 may be about 4480 μm by about 31 m , and a scan width of the laser head 160 may be about 4480 μm . the laser pixels 162 of the laser head 160 may be automatically operated by a computer system such that each of the laser pixels 162 turn on and off according to red , green , and blue color filter patterns . fig6 is a cross sectional view of an exemplary color transcription film according to the present invention . in fig6 , a color transcription film 110 may include three layers : a supporting film 110 a ; a light - to - heat conversion ( lthc ) layer 110 b ; and a color filter layer 110 c . the supporting film 110 a , which may support the lthc layer 110 b and the color filter layer 110 c , may include a high molecular substance , such as polyester and polyethylene , having transparent and high transmittance characteristics in order to transmit a laser beam to the lthc layer 110 b . the lthc layer 110 b may be formed on the supporting film 110 a and may be made of a material that can efficiently convert light into heat energy . accordingly , the lthc layer 110 b may convert light energy from a laser head into heat energy . the lthc layer 110 b may include an organic material , such as carbon black and ir ( infrared ) pigments , or an inorganic material , such as a metal material ( i . e ., aluminum ( al ), metallic oxide , or alloy of the above materials ). the color filter layer 110 c , which may be the layer to be transferred , may be formed on the lthc layer 110 b and may include one of red , green , and blue colors . fig7 a to 7 e are cross sectional views of an exemplary method of fabricating a color filter substrate according to the present invention . here , a color filter substrate of fig7 a to 7 e shows pixels along a line having the same color , for example red , and for convenience of explanation , a laser head may be illustrated to be shortened as compared with a region between black matrixes of a substrate . in fig7 a , a black matrix 105 may be formed on an insulating substrate 100 by depositing a metal material , such as chromium ( cr ), or coating a resin , such as an epoxy . then , the metal material or resin may be patterned through photolithographic processes . in fig7 b , a first color transcription film 120 , which may include a supporting film 120 a , a light - to - heat conversion ( lthc ) layer 120 b , and a color filter layer 120 c , may be disposed over the substrate 100 including the black matrix 105 with the color filter layer 120 c facing the substrate 100 . the first color transcription film 120 may be adhered to the substrate 100 without bubbles , and a laser head 160 may be disposed at a distance over the first color transcription film 100 . then , a laser beam of the laser head 160 may be applied to the first color transcription film 120 in a portion where a first color filter pattern will be formed later as the laser head 160 scans the substrate 130 by reciprocating the laser head 160 along a straight line or moving a stage fixing the substrate 100 thereon along a straight line . in the first color transcription film 120 exposed to the laser beam , the lthc layer 120 b may transform light absorbed from the laser beam into thermal energy , thereby emitting thermal energy . then , the color filter layer 120 c may be transferred onto the substrate 100 due to the emitted thermal energy . in fig7 a to 7 e , the color filter substrate may be a stripe - type , wherein color filter patterns along a line may have the same color . accordingly , a first line may be exposed to the laser beam by moving the laser head along a straight line . however , second and third lines may be skipped . similarly , a fourth line may be exposed to the laser beam . in this manner , all the lines of the first color filter pattern may be exposed . after a first scan , one of the substrate 100 and the laser head 160 is transferred , and the second , third , and fourth scans may be sequentially performed . in fig7 c , the first color transcription film 120 ( in fig7 b ) may be removed after the whole substrate 100 is scanned . here , the color filter layer 120 c corresponding to the lthc layer 120 b exposed to the laser beam may be transferred onto the substrate 100 , while the color filter layer 120 c corresponding to the lthc layer 120 b not exposed to the laser beam may be removed together with the color transcription film 120 ( in fig7 b ). accordingly , a first color filter pattern 125 may be formed both between the adjacent black matrixes 105 on the substrate 100 and on the black matrixes 105 . in the example shown , the first color filter pattern 125 may be a red color filter . scanning traces 130 may be formed along borders between the first , second , third , and fourth scans on the color filter pattern 125 . the scanning traces 130 protrude over the color filter pattern 125 . next , although not shown in the figures , a second color filter pattern and a third color filter pattern may be formed through the same process shown in fig7 b and 7c . the second and third color filter patterns may be green and blue color filters , respectively . next , the substrate 100 having the color filter pattern 125 may be placed into a hardening furnace , and the color filter pattern 125 may be hardened under temperatures within a range of about 200 degrees of celsius to about 300 degrees of celsius . in fig7 d , the substrate 100 including the hardened color filter pattern 125 may be situated onto a stage ( not shown ), and the surface of the color filter pattern 125 may be polished by a chemical mechanical polishing ( cmp ) process using a polisher 150 moved along the surface of the color filter pattern 125 or by moving the stage . accordingly , the scanning traces 130 may be removed and the surface of the color filter pattern 125 may be flattened ( or planarized ). in addition , a surface roughness of the color filter pattern 125 may be improved . the polishing process may be accomplished along an entire surface of the color filter pattern 125 , or may be performed within specified portions of the color filter pattern 125 . in fig7 e , a common electrode 140 may be formed on the color filter pattern 125 by depositing a transparent conductive material , such as indium - tin - oxide and / or indium - zinc - oxide . thus , an overcoat layer may be formed between the color filter pattern 125 and the common electrode 140 may be omitted since the color filter pattern 125 has a flat surface due to the polishing process . according to the present invention , since the scanning traces formed along a border between adjacent scans may be removed through a polishing process , such as a cmp process , a liquid crystal display device having high quality images may be provided . in addition , manufacturing costs may be reduced since the overcoat layer may be omitted . it will be apparent to those skilled in the art that various modifications and variations can be made in the color filter substrate and method of fabricating a color filter substrate of the present invention without departing from the spirit or scope of the invention . thus , it is intended that the present invention cover the modifications and variations of this invention provided that they come within the scope of the appended claims and their equivalents .	8
aspects of the present invention are directed to systems and methods which take into account multiple preemption events . in some embodiments , the invention adjusts to changing backfill window conditions caused by multiple preemption events and canceling low priority jobs which may have advantageously backfilled into the system due to past high priority work . that is , a backfilled job that is low priority , if it needs to be preempted by a high priority job , will be returned to the job queue in its original location . operating in this manner preserves the intent of classic preemption rules : to allow higher priority jobs to run immediately even if low priority work is presently using them . in addition , aspects of the present invention prevent previously preempted low priority work from excessive restart delays due to low priority backfill in the event of high priority preemption . as a further advantage high system utilization is preserved because low priority work may still be advantageously backfilled in the event of a high priority preemption . systems and methods according to the present invention subject low priority backfill to rules that prevents the problems experienced in the current backfill and preemption implementations . fig1 shows an example of a computing system 100 according to an embodiment of the present invention . the computing system 100 may be any type of computing system and may be , for example , a mainframe computer or a personal computer . in some embodiments , the computing system 100 includes a plurality of node clusters 102 . for instance , and as shown in fig1 , the computing system 100 includes node clusters 102 a , 102 b . . . 102 n . each of the node clusters 102 may include a plurality of processing nodes therein . in one embodiment each node cluster 102 includes 16 nodes . it should be understood that the number of nodes per cluster and the number of nodes clusters themselves is not limited in any manner . the term “ node ” as used herein shall refer to an element capable of processing a job either independently or in combination with other nodes . examples of nodes include , but are not limited to , microprocessors , integrated circuits , and the like . in some embodiments , a node cluster may be a cluster of personal computers where the each personal computer may include one or more processing nodes . each of the node clusters 102 may be coupled to a scheduler 104 . the scheduler 104 may , in some embodiments , be a parallel job scheduler such as a tivoli workload scheduler loadleveler from ibm . in general , the scheduler 104 determines how to distribute the jobs contained in a job queue 106 amongst the node clusters 102 in order to efficiently utilize the resources of the computing system 100 . the computing system 100 receives jobs to be performed from a system user 108 and these jobs are placed in the job queue 106 in the order they are received . of course , more than one system users 108 could be connected to the computing system 100 . the job queue 106 and the operation of the scheduler 104 are described in greater detail below . fig2 shows an example of a job queue 106 . the job queue 106 includes , in this example , four jobs , 202 ( referred to as job 1 or j 1 ), 204 ( referred to as job 2 or j 2 ), 206 ( referred to as job 3 or j 3 ), and 208 ( referred to as job 4 or j 4 ). each of these jobs includes a priority rating contained in a priority rating ( or class ) column 210 . for instance , j 1 has a lowp ( low priority ) rating , j 2 has a hip ( high priority ) rating , j 3 has a lowp rating and j 4 has a hip rating . according to classic preemption rules , a hip job will always preempt a lowp job . that is , even if a hip job is received from a user after a lowp job , the computing system will halt ( suspend ) the lowp job and run the hip job if there are not enough nodes to process both jobs simultaneously . in such a case , the lowp is suspended and put on hold until the nodes it was running on become available ( i . e ., after the hip job finishes ). such a preemption rule may be established in the configuration files of the scheduler . as one of skill in the art will realize , different configurations could exist but the following discussion that the above preemption rule is applied . the job queue 106 may also include a state column 212 indicating whether a job is running ( r ) or idle ( i ). the job queue 106 may also include a nodes required column 214 . the values in the node required column 214 represents the number of nodes ( or processors ) in a node cluster that will be needed for a particular process to run . the job queue 106 may also include a time required column 216 indicating how long the job will take to run and a time in column 218 that represents a time that a particular job was submitted to the queue . as shown , the time in column 218 is just an ordered list for ease of explanation but any type of representation of the time a job came in may be utilized . alternatively , the time in column 218 could represent an order that jobs are to be completed or any other type of ordering for jobs to be completed . it should be understood that the job queue 106 shown in fig2 is by way of example only . the job queue may have the same or different columns than those shown in fig2 . the only column that may be needed is one that indicates the priority of a particular job . of course , this information could be in any form and need not necessarily exist in a column as long as it is otherwise associated with a particular job . in general , the job queue is utilized by the scheduler 104 ( fig1 ) to schedule the processing of jobs to be run by the system . fig3 a - 3 f show the usage of particular nodes in a single node cluster . as depicted , the node cluster includes 16 nodes . of course , the node cluster could include any number of node clusters . the description of fig3 a - 3 f below describes the utilization of particular nodes during operation of a computing system that may accept jobs having hip and lowp and references jobs having attributes as shown in fig2 . in particular , jobs 1 - 4 from fig2 are referenced in the following description . in fig3 a - 3 f a node with no shading is idle and shaded node is processing a job . furthermore , a black shaded node is running a hip job and a grey shaded node is running a lowp job . fig3 a shows an example of job 1 running in a 16 node system . each node 301 is shown in grey meaning that it is being utilized by a lowp job . consulting again fig2 , job 1 is rated as a lowp job and its state is running ( r ). further , job 1 is utilizing 16 nodes and has an estimated run time of four hours . job 2 is a hip job and come in after job 1 and requires 1 node . according to classic preemption rules , job 2 preempts job 1 and the nodes take on the state shown in fig3 b . that is , job 1 is not running ( suspended ) and job 2 is running on 1 node , node 1 leaving 15 nodes unutilized . the scheduler attempts to achieve maximal efficiency and , therefore , maximal usage of the nodes . as shown in fig3 b the condition of 15 unused nodes is not consistent with such an operating procedure . thus , the scheduler attempts to utilize the unused nodes for another process . one way in which this may be done is to backfill the unused nodes with another job from the job queue 106 . examining the job queue 106 shown in fig2 , it can be seen that the job 3 will require 8 nodes and may run in one hour . assuming that job 3 comes in at a time less than or equal to one after hour job 2 has begun , job 3 could be run on eight of the 15 available nodes and complete before job 2 does . alternatively , if j 2 and j 3 were placed on the queue simultaneously ( where j 1 was already running on the machine ), in the order indicated in fig2 , j 3 can be started as a backfill event . because j 2 will take 2 hours to complete , the 15 free nodes are available for 2 hours . since j 3 will complete in 1 hour , it is well within the backfill window . as time progresses , this backfill window will become shorter . as long as j 3 is started when the backfill window is 1 hour ( or greater ), j 3 runs as a backfill job with no impact on either j 2 or the planned restart of suspended job j 1 . in such a situation , job 1 would then be able to restart when job 2 completed and the standard procedure of having hip jobs preempt lowp jobs would be met with the added benefit that job 3 also was completed . fig3 c shows hip job job 2 running on node 1 and the backfill job job 3 running on nodes 9 - 16 . having job 3 run in the time available nodes while job 2 was running is referred to herein as “ backfilling ” and any job so running is referred to herein as a “ backfill job .” backfill jobs run in what are referred to herein as “ backfill windows ” which represent a period of time that a certain number of nodes may be available to receive a backfill job . the backfill window may have two dimensions , a temporal dimension representing the amount of time the nodes will be available and a physical dimension representing the number of available nodes . as shown in fig3 d , assume that a new hip job job 4 is submitted a few minutes after jobs 1 - 3 and requires 10 nodes for 10 hours . job 4 preempts job 3 and runs on ten of the free nodes ( nodes 7 - 16 ) while job 2 is processing . the reason that job 4 preempts job 3 is there are only 7 free nodes and job 4 requires 10 nodes , thus , in order for job 4 to run as soon as possible it needs to preempt job 3 . at this time a so called multi - layer preemption event has occurred . in particular , job 1 was preempted by job 2 and job 3 was preempted by job 4 . in order for job 1 to resume it must wait for all the high priority jobs job 2 and job 4 to complete and , under certain conditions , for j 3 to complete as well . fig3 e shows the state of the nodes after job 2 finishes , thus , closing the original backfill window that allowed job 3 to start . job 3 remains suspended because of job 4 . because job 2 now finishes the backfill window that allowed j 3 to start is now void . given the current machine state , job 3 would not be able to backfill since there are six free nodes available for the remainder of the run time of job 4 . in ten hours job 4 finishes and job 3 restarts from suspension . this restart blocks the restart of job 1 until job 3 completes . the restart of job 3 is based on the backfill window established when the high priority job , job 2 , ran . job 1 finally gets to run after all of jobs 1 - 3 are completed . fig3 f shows job 3 running and , as discussed above , job 1 will not be restarted until job 3 is completed . as can be seen from this brief example , in the case where multiple preemptions occur in systems where backfilling is allowed , situations could exist where job 1 never gets completed . aspects of the present invention may ensure that this will not happen . fig4 shows an example of a method by which aspects of the present invention may be implemented . this method may be implemented in the scheduler 104 ( fig1 ) or in any other location in the computer system that has access to allocation of jobs to the nodes contained therein . at a block 402 it is determined if it is acceptable to backfill a job from a job queue . if so , at a block 404 the backfill job is started . that is , as is described above , the job may be placed on nodes that are currently idle , yet protected by a backfill window as the result of a high priority job preempting a previously running low priority job . at a block 406 a higher priority job is received and causes , at a block 408 , the backfill job to be returned to the queue in the location it originally had . returning the backfill job to the job queue at block 408 accomplishes the goal of ensuring that low priority backfill jobs do not end up taking on a higher priority than previously started low priority jobs . in this manner the present invention helps alleviate the problems associated with backfilling that may exist when multilevel preemption events occur . fig5 shows a more detailed depiction of the process of block 408 of fig4 where a backfill job is returned to the job queue . it should be understood that the process shown in fig5 is optional . in the event that the process of fig5 is not implemented the backfill job is merely replaced in the job queue when a hip job preempts it . the process begins at a block 510 where the status of the backfill job is checked . it is then determined , at a block 510 , whether a particular processing threshold has been exceeded . this threshold is based on how much of the backfill job has been completed . in some instances it may be advantageous to store all of the processing that has been performed on the backfill job in a storage location ( available disk space or memory ) so that when the job is restarted this information may be retrieved . of course , in certain instances the job may not have progressed far enough such that the amount of time taken to store the information and then recall when the backfill job restarts results in any advantage . that is , it may take longer to “ checkpoint ” the job than to just restart it when the job reappears at the top of the job queue . the threshold that is checked may be a time running or amount of processing completed and is configurable by a user of the system . if the threshold has not been exceeded , processing progresses to a block 514 where the backfill job is returned to the job queue . if the threshold has been exceeded processing progresses to a block 516 where the processing that has been performed on the job is stored . after the processing of the backfill job has been stored , at a block 518 , the job is returned to the job queue and , in some instances may include an indication of the memory locations where the checkpoint information has been stored . in some embodiments , certain jobs may not be checkpointable . for instance , in the example above , assume job 3 is not checkpointable and it has run for a certain portion of its run time . in some embodiments , jobs that are not able to be checkpointed are tagged as such and the system would not save any job state if the job is placed back onto the job queue . in addition , another class of jobs may also impact storage in such a way that , if they are cancelled after a partial run , there would be undesired side effects . jobs in this category are tagged as not checkpointable , and not able to be backfilled in the case where a preempted backfill window becomes available . these special situations can be handled by flags within the jobs to indicate which different categories the job belongs to . fig6 shows an example of a scheduler 104 according to an embodiment of the present invention . the scheduler 104 shown in fig6 may include a resource manager 602 . the resource manager keeps track of which resources are currently being utilized . for instance , the resource manager may keep a list of machines in the form of a machine list 604 indicating which machines are being used by which jobs and the time requirements associated therewith . for instance , the machine list 604 could include a listing of the node clusters and which nodes within them are being used . fig7 shows an example of a method that may be performed by the resource manager utilizing the machine list . the process begins at a block 702 where a particular machines status is examined . at a block 704 , the machines are ordered based on preemption issues discovered . for instance , a machine ( node cluster ) that does not have a preemption job will be listed higher than one that does . at a block 706 , the list may then be made available to the scheduler . in some embodiments , nodes may be ordered such that free nodes are at the top of the list , busy nodes come next and then preempted nodes are ordered from a lowest to highest level of preemption . referring again to fig6 , the resource manager may perform the steps shown in fig7 and release the information to the scheduler 104 . fig8 shows a process by which the scheduler may operate in order to carry out the multi - level preemption according to the present invention . the process shown in fig8 assumes that a machine is currently running with a number of jobs already being processed . at a block 802 a request for a hip job is received . at a block 804 it determined if any of the node clusters , considered either alone or in combination , include enough open nodes to run the hip job . if so , at a block 818 the hip job has nodes in one of the node clusters allocated for it and it is run . the allocation of nodes may include updating the status of particular nodes within a node cluster in the machine list as described above . if there are no nodes available , or not enough nodes available to run the hip job , then the node clusters are examined to see if any have lowp jobs running on them that may be preempted at a block 806 . the determination made in block 806 may include scanning the machine list which contains the status of the nodes in node clusters of the computing system . it will be understood that a hip job may run on a combination of free nodes and nodes that previously had lowp job running on them . in other words , to the extent additional nodes beyond available free nodes are needed , those nodes may be made available by preempting lowp jobs . in the event that no lowp jobs are running that may be preempted , i . e ., all of the nodes are running high priority jobs , the current scheduler pass moves to the next job and processing returns to block 804 . that is , if a job cannot be scheduled , it is skipped and the scheduler considers other jobs in the list . at the next pass , all idle jobs are again checked to see if they can now run ( due to changes in node availability ). in the event that there is a lowp job running on a particular node in certain clusters that may be preempted ( i . e ., the lowp job is utilizing the same or more nodes than are needed by the hip job ), at a block 810 it is determined whether this lowp is a backfill job . in some embodiments , the probability that a node having a backfill job running on it will be selected may be reduced by placing nodes having backfill jobs running on them at the bottom of the machine list and scanning the machine list from top to bottom when searching for nodes having lowp jobs in block 808 . if the lowp job is not a backfill job , at a block 820 the job is preempted . in some instances , preempting the job may cause the node or node cluster the job was running on to be placed at the bottom of the machine list . the hip job is then allocated and run at a block 818 . of course , as one of skill in the art will realize , multiple lowp jobs may need to be preempted in order to free up the required resources . as such , the process performed in block 820 may involve preempting multiple lowp jobs . if the lowp was a backfill job , a checkpointing routine may be run . that is , if the lowp job is a backfill job as determined at block 810 , at a block 812 it is determined if the backfill job should be checkpointed . if so , at a block 814 the processing that has been performed on the backfill job is saved . regardless of whether checkpointing is required , at a block 816 the backfill job is returned to the job queue . as discussed above , returning the backfill job to the job queue ensures that a lowp backfill job will not , by virtue of being a backfill job , achieve a status that is higher than a lowp job that was previously started but is suspended because it was preempted . as described above , embodiments can be embodied in the form of computer - implemented processes and apparatuses for practicing those processes . in exemplary embodiments , the invention is embodied in computer program code executed by one or more network elements . embodiments include computer program code containing instructions embodied in tangible media , such as floppy diskettes , cd - roms , hard drives , universal serial bus ( usb ) flash drives , or any other computer - readable storage medium , wherein , when the computer program code is loaded into and executed by a computer , the computer becomes an apparatus for practicing the invention . embodiments include computer program code , for example , whether stored in a storage medium , loaded into and / or executed by a computer , or transmitted over some transmission medium , such as over electrical wiring or cabling , through fiber optics , or via electromagnetic radiation , wherein , when the computer program code is loaded into and executed by a computer , the computer becomes an apparatus for practicing the invention . when implemented on a general - purpose microprocessor , the computer program code segments configure the microprocessor to create specific logic circuits . while the invention has been described with reference to exemplary embodiments , it will be understood by those skilled in the art that various changes may be made and equivalents may be substituted for elements thereof without departing from the scope of the invention . in addition , many modifications may be made to adapt a particular situation or material to the teachings of the invention without departing from the essential scope thereof . therefore , it is intended that the invention not be limited to the particular embodiment disclosed as the best mode contemplated for carrying out this invention , but that the invention will include all embodiments falling within the scope of the appended claims . moreover , the use of the terms first , second , etc . do not denote any order or importance , but rather the terms first , second , etc . are used to distinguish one element from another . furthermore , the use of the terms a , an , etc . do not denote a limitation of quantity , but rather denote the presence of at least one of the referenced item .	6
various details of the state of the art in the area of sequencing - by - synthesis caused us to re - think the approach . we first considered the size of the 3 ′- cap in light of the crystal structures of various polymerases . both the mom and allyl groups , although small , are still too large to fit comfortably into the active site based on crystallographic analysis ( see [ eva00 ] and papers cited therein ). these groups each contain three heavy atoms , defined here to be non - hydrogen atoms , in addition to the 3 ′- oxygen being protected . the essence of the instant invention is that a 3 ′- blocking group that has fewer than three heavy atoms is required for an efficient sequencing by synthesis architecture , either with natural polymerases or with polymerases in which one of the amino acids in contact with the ribose ring is mutated . to implement this invention , the 3 - o - amino group is used as a removable protecting group for the sequencing - by - synthesis scheme ( fig1 ). the 3 ′- o - amino group is chosen because it is as small a moiety as can be imagined to form a stable 3 ′- o blocking group . the small size of the 3 ′- modification makes it most likely to be accepted by dna polymerases during template - directed dna polymerization [ hen04 ]. further , contact by dna polymerases with the 3 ′- end of the incoming triphosphate is frequently made with an amino acid with an aromatic side chain ( phe or tyr ) [ gar99 ]. the size of this can be reduced ( to his ), generating the possibility that if any particular natural polymerase does not work , then these can be mutated , followed by a round of in vitro directed evolution [ gha01 ], to generate polymerases that accept 3 ′- o - amino triphosphates with acceptable specifications . a working sequencing - by - synthesis system that permits parallel ( for example , a 100 × 100 array ) sequencing or single nucleotide sequencing would be extremely useful , provided that the reads are & gt ; 25 nucleotides in length ). even if the reads are short , sequencing - by - synthesis could be very useful in the laboratory and , perhaps , in personalized medicine . for example , one can imagine the use of a sequencing - by - synthesis chip for resequencing a specific locus within a genome to identify polymorphisms in a population . the hydroxylamine functionality is stable in water , and displays several other advantages : ( a ) a set of 3 ′- o - amino - 2 ′- deoxynucleosides ( fig2 ) is already known in the literature [ dec90 ][ kon85 ][ bur94 ][ coo94 ]. they are directly synthesizable from the xylo - 2 ′- deoxyribonucleosides via a mitsunobu reaction with n - hydroxyphthalimide ( fig2 ). from this work , we know that the o — nh 2 group is compatible with dna bases ( pace the ability of hydroxylamine and methoxyamine to be mutagenic ; see below ). ( b ) the 3 ′- o - amino - 2 ′- deoxynucleoside blocking group is small , even smaller than the speculative — osh unit ( which was considered ) and the azido unit ( which is incorporated by reverse transcriptases when they accept azidothymidine triphosphate , for example ). ( c ) the 3 ′- o - amino - 2 ′- deoxynucleoside functionality has much of the hydrogen bonding potential of the 3 ′- oh group . while not wishing to be bound by theory , these derivatives may form a network of hydrogen bonds to the catalytic magnesium ion , as suggested by crystallography for the natural substrate , and therefore fitting into the active site of various polymerases . ( d ) in some cases , a polymerase can be improved by replacing the phe or tyr ( depending on the polymerase ) [ eva00 ] [ gar04 ] that blocks the 3 ′- position of the incoming triphosphate with a slightly smaller aromatic group , h is or phe ( respectively ). ( e ) a large number of reagents are known that cleave the n — o linkage in hydroxylamines and o - alkoxyamines . these are discussed in greater detail below . oxidative conditions are provided by bleach , nitroso compounds , iodate , or potassium ferrate in 1 m nacl , 50 mm potassium phosphate buffer , 25 ° c . ; this generates the free — oh group and n 2 o , which is trapped . reducing agents include catalytic hydrogenation . the preferred approaches include addition - elimination cycles where the amino group of the alkoxyamine adds to an electrophile ( such as maleimide or a naphthoquinone ) and then ejects the alcohol as a leaving group . ( f ) the 3 ′- o - amino - 2 ′- deoxynucleosides offer a handle that can permit the selection of polymerases that incorporate them , should mutagenesis studies not succeed . the water - oil emulsion system [ gha01 ] to select for thermostable polymerases is used to select polymerases that incorporate 3 ′- o - amino - 2 ′- deoxynucleosides to their own gene where the genes are recovered by an aldehyde column that captures 3 ′- o - amino - 2 ′- deoxynucleosides as oximes . with this 3 ′- o blocking group , other features of the architecture of the state - of - the - art sequencing - by - synthesis approach could be adopted . in particular , the same cleavable linkers that hold the fluorescent labels to the nucleobases would be used . these linkers might also be designed such that they can be cleaved by whatever reagent was used to remove the amino group from the terminal 3 ′- o - amino - 2 ′- deoxynucleoside . using the o - amino 3 ′- blocking group in a sequencing - by - synthesis strategy is not constrained by the reactivity of n - alkoxyamines . these are nucleophiles , and simple members of this class of compound ( hydroxylamine and methoxyamine in particular ) are known to react with dna , predominantly by replacing the exocyclic amino groups of cytosine and , to a lesser extent adenine , with the alkoxyamine to generate 4 - methoxycytosine and 4 - methoxyadenine [ koc69 ]. this is not a serious problem here . first , the reaction of alkoxyamines with cytidine proceeds slowly at neutral ph , even when the concentration of alkoxyamines is high . the reaction is slower with methoxylamine than hydroxylamine , and it is still slower with the secondary n - alkoxyamines , such as a 3 ′- onh 2 unit on a nucleoside derivative . while not wishing to be bound by theory , it appears that these structural features explain why the 3 ′- o - amino unit does not react rapidly with cytosine and adenosine nucleosides [ dec90 ]. for a typical alkoxyamine , pk a ≈ 4 . 6 . the 3 ′- o - amino group is neutral at physiological ph . the triphosphates of the 3 ′- o - amino - 2 ′- deoxyribonucleosides are prepared using the ludwig - eckstein synthetic procedure [ lud89 ] ( fig3 ). our preferred route for generating triphosphates applies the ludwig - eckstein procedure to the precursor where the o — nh 2 group is protected as an fmoc amide , a trifluoroacetyl amide , or transiently as an oxime with acetone . less preferably , but as an alternative , is to use the ludwig - eckstein procedure with the unprotected 3 ′- o - amino - 2 ′- deoxynucleoside . a variety of reagents and conditions cleave n — o bonds . the instant invention offers a number of these , so that chemists can chose a procedure to fit the particular side chain chemistry that is used to append a readable tag to the nucleobases . most preferably , the reaction that removes the 3 ′- oh amino group is done in water . this is desired so that the integrity of the double helix is retained . it is possible , in a sequencing - by - synthesis architecture , to re - anneal following a treatment by a reagent that denatures the double helix , making the requirement for aqueous chemistry not absolute . this is less preferable , however , for practical use . therefore , most preferable is an aqueous deblocking chemistry , with organic co - solvents present to less than 50 % of the total by volume , under conditions where the double helix does not disassociate or precipitate . for example ( depending on the salt concentration ), solvents such as methanol or ethanol ( to ca . 50 %), tetrahydrofuran or dioxane ( to 40 %), or denaturants ( e . g ., dimethylformamide , dimethylsulfoxide to ca . 25 %) may be used . a substantial literature covers a large number of procedures to cleave the n — o bond of an r — onh 2 unit . as summarized below , the instant invention offers ca . two dozen different reagents that might be used to cleave the n — o bond under conditions sufficiently mild that they will not degrade dna , and not denature the primer - template duplex . most of these rely on the unique reactivity of the pair of heteroatoms ( o — n ), both having unshared pairs of electrons , reactivity that is not found elsewhere in dna . thus , the o — n unit has particularly low basicity , particularly good electron donation properties , and particularly high nucleophilicity . it shares these features with hydrazine and peroxide , as is well known in the art under the rubric of the “ alpha effect ”. this means that against a variety of reagents , both electrophilic and oxidizing , the alkoxyamine group reacts first , before other parts of the dna molecule . this suggests that competing reactivity is easily managed , using conditions that are beneficial in general for other reasons , including low reagent concentrations , low temperatures , rapid treatments , and rapid quenches . these conditions are desired by most sequencing - by - synthesis architectures . the species that is being deblocked is known as an o - alkylhydroxylamine . reagents are known for the cleavage of the n — o bond many other derivatives , including o - acyl hydroxylamines , n - acyl hydroxylamines , and oximes ( where the o is — oh ) ( fig4 ). these substrates have been chosen because they are intermediates in natural product syntheses of various types . many of these are homogeneous , and many are known to work in aqueous media . however , it may be necessary to transform the 3 ′- terminally blocked — o — nh 2 unit into one of these derivatives . for example , preparing an oxime from the 3 ′- o — nh 2 unit is direct ; one simply stirs with an aqueous solution of the appropriate ketone or aldehyde . the nature of the ketone or aldehyde can be adjusted to adjust the reactivity of the species . preparing the o - alkylhydroxamic acid requires acylation . here , mild acylation reagents in aqueous media are expected to prefer the hydroxylamine , with its enhanced nucleophilicity over the exocyclic amino groups of the nucleobases . thus , reagents that cleave all three are considered here . the nh 2 group is susceptible to oxidation that leads to fragmentation . the simplest reagent is dilute hypochlorite in a process that has been known for half a century [ ril54 ]. in addition , nitric oxide and other nitrosating agents may be used . these have been reviewed recently by corsano et al . [ cor01 ]. in particular , the reaction of o - alkoxyamines with nitroso compounds ( e . g ., nitrosobenzene ) generates the diazo compound ( in this case ph — n ═ n — or ), which can be fragmented to give the alcohol roh [ mas88 ][ mas90 ][ pat77 ][ ver91 ]. dna is not easily degraded by hypochlorite and other oxidizing agents ( see literature in this area [ ber90 ] [ hay71 ] [ hoy73 ] [ pat72 ] [ whi97 ] [ whi99 ]). hypochlorite is a product of biological systems ( through the reaction of hydrogen peroxide and chloride catalyzed by myeloperoxidase in mammalian neutrophils ), as well as being ubiquitous in the environment ( in swimming pools , food sanitizers , and the paper industry ). in a relatively thorough recent study , whiteman et al . [ whi97 ] exposed calf thymus dna to hypochlorite at 37 ° c . for one hour at ph 7 . 4 , and quantitated various oxidation products of dna . they found pyrimidine oxidation products ( thymine glycol ( cis / trans ), 5 - hydroxycytosine , 5 - hydroxyuracil , 5 - chlorouracil , and 5 - hydroxyhydantoin ), but not purine oxidation products ( 8 - hydroxyguanine , 2 - and 8 - hydroxyadenine , fapy guanine , fapy adenine ). conversion was strongly dependent on concentration . at 0 . 1 mm hocl concentrations , total modified base concentrations are between 1 and 5 nanomoles per mg of dna . thus , this represents a conversion of ca . 0 . 1 %, in one hour at 37 ° c . as the alkoxylamine reaction is complete in seconds at lower temperature , this reaction has utility . other oxidizing agents are reported to cleave the n — o bond in oximes . these include caro &# 39 ; s acid [ mov00 ] and iodate [ mah97 ]. iodate and dna are quite compatible , as is well known from the fact that iodate is a product in the periodate - mediated cleavage of rna , a process that is widely used in nucleoside chemistry . in these cases , the reaction appears to be done under aqueous conditions . in general , however , the procedure is well documented for oximes having a free oh group ( see review in [ cor0 ]. n - bromosuccinimide and n - bromoacetamide were also found to be efficient and selective reagents for the mild oxidative cleavage of oximes . perchlorate and periodate are also able to convert a variety of oximes into the corresponding carbonyl compounds . these reactions are reported at 0 ° c ., leaving alkaloid nitrogens untouched . but many of these reagents ( such as the dess - martin periodinane ) require a free oh on the oxime . our presently preferred method for oxidative cleavage is treatment with nitrous acid at ph 4 - 5 , which cleaves the onh 2 group at a rate over 100 times faster than it deaminates guanine , or treatment with a nitrite ester ( e . g ., ethyl nitrite ) at ph 7 - 8 . the classical way in synthetic organic chemistry to cleave the n — o bond is to treat the linkage with dihydrogen in the presence of a pt or pd catalyst [ cor83 ] [ nai94 ]. this reaction proceeds quantitatively , can occur in aqueous solvents , and leaves dna undamaged . the primary disadvantage of this process is that catalytic hydrogenation requires a heterogeneous catalyst which may not be accessible to dna immobilized on a chip . no work has evidently been done to identify soluble catalysts that achieve the same end . a variety of reagents have been used to reductively cleave n — o bonds under mild conditions . these are reviewed in [ khl03 ]. one of the earliest of these , introduced by keck [ kec79 ], involves sodium amalgam . the reaction is reported in ethanol as solvent . best results are obtained when the reaction mixture was buffered with four equivalents of sodium hydrogen phosphate . several low oxidation states metal cations that dissolve in water cleave n — o bonds . these were discovered in the late 1960 &# 39 ; s and early 1970 &# 39 ; s in programs to synthesize antibiotics where oximes were precursors . many of these work in water under conditions where duplex dna is expected to be stable . one of these was provided by timms and wildsmith in a process that cleaved the n — o bond of an oxime in a precursor for the synthesis of erythromycin [ tim71 ]. here , heterogeneous catalysts were explicitly not desired ( as is the case in sequencing - by - synthesis ), and special effort was made to obtain a reagent that could exist in homogeneous solution with the reactant . clean and quantitative conversion was obtained using a 15 % solution of ticl 3 in water buffered with sodium acetate . two equivalents of the reagent were required , and the reaction was easily followed by the loss of the characteristic color of titanium ( iii ). conversion was complete within five minutes at room temperature . the only negative feature of this reaction is the fact that it is reported for a free oxime , rather than an o - alkyloxime . timms and wildsmith also report two other low valent metals suitable for reduction of an oxime in aqueous solution . these are divalent vanadium ( prepared by zn / hg reduction of vanadyl sulfate ), samarium [ chi96 ] and divalent chromium ( where acetate buffer was not used ). molybdenum hexacarbonyl mo ( co ) 6 is widely used in synthesis , as it cleaves the o — n bond where both the oxygen and the nitrogen have substitutents . this reagent is used in water - acetonitrile mixtures [ nit85 ] [ khu04 ] [ maro5 ] [ you06 ]; the species is not soluble in pure water . active agents having the formula mo ( co ) n ( ncr ) 6 - n , which are more soluble in water , may also be used . the fact that ticl 3 works directly on an oxime was cited by [ tim71 ] as an advantage over other procedures that use low valent metals as reducing agents , but are reported for o - acylated oximes . the procedure of corey and richman [ cor70 ], which involves the treatment of an o - acyl oxime with chromium ( ii ) cleaves the n — o bond of o - acetyl oximes in aqueous solution . the reaction is reported to proceed in high yield at room temperature over 24 hours . only incomplete experimental details are provided in the original paper ; in particular , the paper does not report whether the reaction also works with o - alkylated oximes . another potentially suitable method was offered by keck [ kec95a , b ] using smi 2 . some of these reagents may have utility to regenerate the 3 ′- hydroxyl group , allowing the next cycle in the sequencing - by - synthesis strategy to occur . in these procedures , the first step involves the reaction of a carbonyl compounds with the nh 2 group to create an oxime . acetone appears to be perfectly acceptable for this purpose . this creates 2 ′- aminopropane as a side product , which is innocuous . a larger aldehyde having fluorescence can also be used . this generates the corresponding amine , which can be detected as a way to monitor the progress of the reaction . in the second step , the trivalent cation is introduced as its chloride salt in dilute aqueous solution . a third approach , which is presently preferred , involves neither oxidation nor reduction , but rather an addition / elimination sequence . this can be done with a wide range of electrophiles . the general strategy involves the attack of the amino group of the alkoxylamine upon an electrophilic molecule that , after the appropriate arrowisms , produces a push of electrons that ejects the oxygen of the alkoxylamine as a leaving group . a schematic for these is shown in fig5 . the electrophile can be maleimide [ sek97 ] [ sek99 ], nitrobenzene [ nik00 ], or nitroolefins [ ima96 ] [ ima97 ]. one method potentially involves the reaction of the o - alkoxylamine with a quinone , preferably a 1 , 4 - naphthoquinone [ bit94 ], and more preferably a 1 , 4 - naphthoquinone that carries on the second ring an ionic group ( such as a sulfonate or carboxylate group ) that makes the quinone soluble in aqueous media . the reactions leading to the removal of the amino group from the oxygen all proceed under mild conditions ( fig5 ). while not wishing to be bound by theory , the utility of this reagent may be diminished by the presence of multiple electrophilic sites in the species , which creates dead - end products that are not easily converted to the desired product . while the reagents described give the new compositions utility in a variety of settings , the instant application discloses additional reagents for cleaving a 3 ′- onh 2 blocking group . these fall into two classes . class 1 . reagents that react directly with the 3 ′- onh 2 blocking group , and generates the 3 ′- oh unit without the isolation of an intermediate , or the addition of a subsequent reagent in a second step . these include reagents shown in fig1 . while not wishing to be bound by theory , these figures also illustrate mechanisms by which these reagents are presumed to act . class 2 . reagents that react directly with the 3 ′- onh 2 blocking group to form an intermediate , which then generates the 3 ′- oh unit . these include reagents shown in fig1 . while not wishing to be bound by theory , these figures also illustrate mechanisms by which these reagents are presumed to act . we next consider fluorescent tags that might be used in conjunction with a 3 ′- onh 2 reversible blocking group . classically , fluorescent groups are appended to the five position of pyrimidines , or to the 7 - position of 7 - deaza purines . many groups have developed chemistry for preparing these classical derivatives ( see for example [ hob91 ], see also our work [ hel02 ] [ roy04 ] and references cited therein for a “ two moving target ” optimization of polymerases and the 5 - position linker ). tags at this position are accepted by polymerases [ hel02 ], and fluors at this positions are combined with modifications in the sugar to do dideoxy sequencing . in practice , any linker that can be cleaved to release the fluorescent product allows the loss of the fluor prior to the next extension reaction , preventing the fluor from cycle n from confusing the signal from the fluor appended at cycle n + 1 . alternatively , with strategic choice of the fluor , the fluor can itself be destroyed by chemical transformation , including by reduction ( e . g . of cyanine fluors ) or by bleach . a second consideration reflects the fact that the rule - based molecular recognition properties displayed by dna and rna are unique in chemistry , and easily disrupted . as was demonstrated in earlier work [ hel02 ], addition of extensive functionality to every nucleobase may disrupt the rule based molecular recognition . therefore , the preferred strategy removes as much of the tag as possible at each cycle , and arranges to have what is left behind be as hydrophilic as possible . this is , of course , in addition to the need to have inexpensive and readily accessible linkers . the presently preferred linker , after cleavage , leaves behind a — ch ═ ch — ch 2 oh group . this is preferable to the — ch ═ ch — ch 2 — nh 2 group , which places a positive charge on the side chain . it is also preferable to the — cc — ch 2 — oh , — c — ch 2 — sh , and — cc — ch 2 — nh 2 units , for reasons of record [ hel02 ], although these may also be used . last , the longer linkers — cc — ch 2 — ch 2 — oh , — cc — ch 2 — ch 2 — sh , — cc — ch 2 — ch 2 — nh 2 , — ch ═ ch — ch 2 — ch 2 — nh 2 , h ═ ch — ch 2 ch 2 — oh , and — ch ═ ch — ch 2 — ch 2 — sh linkers , which have enhanced stability , although they each leave an extra atom once cleavage is complete . each of these linkers can carry a fluorescent tag appended by an ester , amide , or disulfide linkage , appropriately . the presently preferred — ch ═ ch — ch 2 oh linking group has certain advantages , however . first , the allyl group stabilized duplexes when attached to the 5 - position of pyrimidines . further , the — oh terminus is uncharged , yet hydrophilic . most significantly , however , the — oh terminus can be left behind with the reagent that cleaves the 3 ′- onh 2 group , if the fluor is attached to the linker via the — o — nh - tag unit . this can be coupled to the 5 - iodopyrimidine and the 7 - iodo - 7 - deazapurine units using the synthetic intermediate where the boc - nh — ch 2 — ch 2 — n - fmoc unit , which is then attached to a standard fluor ( a cyanine dye for single molecule sequencing , or a rhodamine , bimane , dyes with large stokes shift , and other molecules ). these are the presently preferred linkers in large part because they can be cleaved from the nucleobase using the reagent that is used to cleave the 3 ′- o blocking group . kondo et al . nearly two decades ago reported the synthesis of the first 3 ′- o - amino - 2 ′- deoxynucleoside [ kon85 ]. subsequently , de clerq prepared a complete set of 3 ′- o - amino - 2 ′- deoxynucleosides , and reported their syntheses in the european patent literature [ dec90 ]. the team at isis led by cook also generated these as well as part of their program in antisense nucleic acid analogs [ coo94 ]. finally , in 1994 , burgess and his coworkers reported the synthesis of dinucleotides joined via an n — o linker in a synthesis that began with the 3 ′- o - amino - 2 ′- deoxynucleoside [ bur94 ] ( fig2 , see also [ oga98 ]). these research groups prepared these compounds because they were seeking to generate nucleic acid analogs where the anionic phosphodiester bond was replaced by an uncharged linker . it does not appear that they considered the possibility of using the 3 ′- o - amino moiety as a blocking group for a sequencing - by - synthesis architecture . the uncharged n - o linker was viewed as a useful replacement for the charged phosphodiester linker . coupling could be easily achieved via reaction of the 3 ′- o - amino - 2 ′- deoxynucleoside with an aldehyde on the next nucleotide building block . these and other uncharged dna analogs were hoped to be able to passively enter cells , and to continue to bind to natural dna and rna following watson - crick pairing rules . the antisense strategy fell out of favor when this was found not to be the case . nevertheless , the activity left behind a rich literature , which makes the synthesis of the needed 3 ′- o - amino - 2 ′- deoxynucleosides well precedented . this notwithstanding , no route was available for preparing the triphosphates , which are new compounds disclosed in the instant invention for the first time . these can be prepared by the route disclosed in fig3 ). the xylo - nucleoside analogs are synthesized under mild conditions from the 5 ′- trityl - or 5 ′- dimethoxytrityl - nucleoside derivatives by mitsunobu reaction with benzoic acid , followed by aminolysis of the resulting benzoate with nh 4 oh . representative procedures are given below : 5 ′- o - trityl - xylothymidine . thymidine ( 4 . 8 g ; 20 mmol ), dmap ( 1 . 2 g ; 10 mmol ) and triethylamine ( 5 . 6 ml ; 40 mmol ) are dissolved in anhydrous pyridine ( 70 ml ) at room temperature . tritylchloride ( 11 . 2 g ; 40 mmol ) is added and the mixture is stirred at room temperature , leading to the precipitation of hcl salts . after 3 days , tlc ( ch 2 cl 2 : meoh = 10 : 1 ) is used to show ca . 90 % conversion . the mixture is then cooled to 0 ° c . methanesulfonyl chloride ( 1 . 9 ml ; 25 mmol ) and triethylamine ( 3 . 5 ml ; 25 mmol ) are added and the mixture is stirred at room temperature for 2 h . the hcl salts are removed by filtration , and the filtrate is concentrated in vacuo . ethanol ( 130 ml ) and aqueous naoh ( 1 . 5 m ; 65 ml ) are added and the mixture is heated at reflux for 2 h . the reaction is quenched by the addition of aqueous hcl ( 1 m ; 80 ml ) and the solvents are removed in vacuo . aqueous work - up ( ch 2 cl 2 ) and flash liquid chromatography ( silica , eluent ch 2 cl 2 : meoh = 30 : 1 to 10 : 1 ) gives 5 ′- o - trityl - xylothymidine ( expected 5 . 9 g ; 61 % overall ) as a colorless foam . 1 h - nmr ( cdcl 3 ; 300 mhz ): δ ( ppm )= 1 . 74 ( d , j = 0 . 8 hz , 3h ); 2 . 22 ( dd , j = 1 . 9 , 15 . 0 hz , 1h ); 2 . 46 - 2 . 59 ( m , 1h ); 3 . 28 ( br s , 1h ); 3 . 45 - 3 . 68 ( m , 2h ); 4 . 02 - 4 . 08 ( m , 1h ); 4 . 40 - 4 . 44 ( m , 1h ); 6 . 17 ( dd , j = 2 . 2 , 8 . 0 hz , 1h ); 7 . 20 - 7 . 50 ( m , 15h ); 7 . 60 ( d , j = 1 . 0 hz , 1h ); 9 . 59 ( br s , 1h ). 5 ′- o - trityl - 3 ′- o - phthalimido - thymidine . 5 ′- o - trityl - xylothymidine ( 1 . 9 g ; 4 mmol ), triphenylphosphine ( 1 . 3 g ; 5 mmol ) and n - hydroxyphthalimide ( 815 mg ; 5 mmol ) are dissolved in thf ( 60 ml ) at 0 ° c . diisopropylazodicarboxamide ( diad , 965 / l ; 5 mmol ) is added drop wise , and the reaction mixture is stirred as the temperature rises from 0 ° c . to room temperature . after 15 h , the reaction was quenched by the addition of h 2 o ( 100 μl ), and the reaction mixture is concentrated in vacuo . flash liquid chromatography ( silica , eluent etoac : hexanes = 1 : 1 to 3 : 1 ) gives 5 ′- o - trityl - 3 ′- o - phthalimido - thymidine ( expected 3 . 4 g ; ca 3 . 5 mmol nucleoside ; 88 %) as a colorless foam . the material may be contaminated with ph 3 p ═ o , but is used for the next step without further purification . 1 h - nmr ( cdcl 3 ; 300 mhz ): a ( ppm )= 1 . 48 ( d , j = 0 . 9 hz , 3h ); 2 . 34 - 2 . 42 ( m , 1h ); 2 . 84 ( ddd , j = 1 . 7 , 4 . 8 , 14 . 0 hz , 1h ); 3 . 48 ( ddd , j = 3 . 2 , 10 . 0 , 35 . 0 hz , 2h ); 4 . 50 - 4 . 54 ( m , 1h ); 5 . 07 - 5 . 13 ( m , 1h ); 6 . 60 ( dd , j = 5 . 6 , 8 . 0 hz , 1h ); 7 . 16 - 7 . 85 ( m , 38h ); 9 . 08 ( br s , 1h ). 3 ′- o - amino - thymidine . hydrazine monohydrate ( 7 ml ) is added to a suspension of 5 ′- o - trityl - 3 ′- o - phthalimido - thymidine ( 2 . 9 g ; ca . 3 mmol nucleoside , contaminated with some ph 3 p ═ o ) in ethanol ( 30 ml ), and the solution is heated under reflux for 2 h . the ethanol is removed in vacuo and the resulting mixture is partitioned between ch 2 cl 2 ( 100 ml ) and aqueous nacl ( 50 % sat . ; 100 ml ). the organic phase is separated and concentrated in vacuo to give a colorless foam , which is redissolved in anhydrous dichloromethane ( 20 ml ). a solution of zinc chloride etherate ( 1 m in et 2 o ; 30 ml ; 30 mmol ) is then added . after a few minutes , the product starts to precipitate . after 30 minutes , the solution is diluted with ch 2 cl 2 ( 100 ml ) and the precipitate removed by filtration . the solids are partitioned between water ( 20 ml ) and ch 2 cl 2 ( 20 ml ). the aqueous phase is separated and lyophilized . the crude product is purified by reverse phase hplc ( c 18 , gradient 0 - 5 % acetonitrile in water over 20 minutes ) to give 3 ′- o - amino - thymidine ( expected 340 mg ; 44 % overall ) as a colorless foam . 1 h - nmr ( dmso - d 6 ; 300 mhz ): δ ( ppm )= 1 . 77 ( d , j = 0 . 7 hz , 3h ); 1 . 97 - 2 . 07 ( m , 1h ); 2 . 29 ( ddd , j = 0 . 7 , 5 . 9 , 13 . 7 hz , 1h ); 3 . 50 - 3 . 66 ( m , 2h ); 3 . 99 - 4 . 03 ( m , 1h ); 4 . 16 - 4 . 20 ( m , 1h ); 5 . 08 ( t , j = 5 . 1 hz , 1h ); 6 . 10 - 6 . 16 ( m , 3h ); 7 . 73 ( d , j = 1 . 0 hz , 1h ); 11 . 27 ( br s , 1h ). 13 c - nmr ( dmso - d 6 ; 75 mhz ): a ( ppm )= 12 . 3 , 35 . 7 , 62 . 1 , 83 . 7 , 83 . 7 , 83 . 9 , 109 . 5 , 136 . 0 , 150 . 5 , 163 . 7 . triphosphates are synthesized using an adaptation of the ludwig - eckstein procedure . the amino group is first protected by fmoc to prevent phosphorylation of this amine . the protection also enhances the solubility of the nucleoside . 3 ′- o -( fmoc ) amino - thymidine . 3 ′- o - amino - thymidine ( 129 mg ; 0 . 5 mmol ) and sodium carbonate ( 53 mg ; 0 . 5 mmol ) are dissolved in water ( 1 . 5 ml ). fmoc - osucc ( 202 mg ; 0 . 6 mmol ) is dissolved in dioxane ( 1 . 5 ml ). the two solutions are then mixed , and the mixture is stirred at room temperature for 3 h . the mixture is partitioned between etoac ( 20 ml ) and aqueous nacl ( 50 % sat ., 20 ml ). the organic phase is concentrated in vacuo and the residue purified by flash liquid chromatography ( silica , eluent etoac : hexanes = 1 : 1 to pure etoac ) to give 3 ′- o -( fmoc ) amino - thymidine ( expected 122 mg ; 52 %) as a colorless solid . 1 h - nmr ( cdcl 3 ; 300 mhz ): δ ( ppm )= 1 . 92 ( d , j = 1 . 0 hz , 3h ); 2 . 45 ( m , 1h ); 2 . 62 ( m , 1h ); 3 . 75 ( m , 1h ); 3 . 92 ( m , 1h ); 4 . 16 ( d , j = 2 . 4 hz , 1h ); 4 . 24 ( t , j = 6 . 0 hz , 1h ); 4 . 57 ( t , j = 5 . 7 hz , 2h ); 6 . 06 ( dd , j = 6 . 4 , 8 . 8 hz , 1h ); 7 . 29 - 7 . 48 ( m , 4h ); 7 . 58 ( d , j = 7 . 8 hz , 2h ); 7 . 77 ( d , j = 7 . 5 hz , 2h ); 8 . 13 ( br s , 1h ). 3 ′- o -( fmoc ) amino - thymidine - 5 ′- triphosphate . following the ludwig - eckstein procedure , 3 ′- o -( fmoc ) amino - thymidine ( 111 mg ; 0 . 23 mmol ) is rendered anhydrous by coevaporation with pyridine . the residue is redissolved in anhydrous pyridine ( 230 μl ) and anhydrous dioxane ( 690 μl ). a freshly prepared solution of 2 - chloro - 4h - 1 , 2 , 3 - dioxaphosphorin - 4 - one ( 73 mg ; 0 . 36 mmol ) in anhydrous dioxane ( 210 μl ) is then added at room temperature under stirring . after 10 minutes , a mixture of bis ( tributylammonium ) pyrophosphate ( 127 mg ; 0 . 27 mmol ; 1 . 6 eq . bu 3 n per pyrophosphate ) and tributylamine ( 212 μl ; 0 . 89 mmol ) in anhydrous dmf ( 640 μl ) was added . after a further 10 minutes , a solution of diiodine in pyridine / water ( 98 / 2 , v / v ; 1 % iodine ; 4 . 5 ml ) is added . after 15 minutes , excess diiodine is reduced by the addition of a few drops of aqueous na 2 so 3 ( 5 %; ca 0 . 3 ml ). the mixture is then concentrated in vacuo . the residue is redissolved in water ( 2 ml ) and purified by rp - hplc ( c 18 , gradient 0 - 35 % acetonitrile in 10 mm triethylammonium acetate over 37 minutes ) to give 3 ′- o -( fmoc ) amino - thymidine - 5 ′- triphosphate as a colorless foam . 1 h - nmr ( d 2 o ; 300 mhz ): a ( ppm )= 1 . 72 ( s , 3h ); 1 . 81 - 1 . 91 ( m , 3h ); 3 . 91 ( m , 3h ); 4 . 01 ( m , 1h ); 4 . 29 ( m , 1h ); 4 . 41 ( m , 1h ); 5 . 89 ( m , 1h ); 7 . 11 - 7 . 20 ( m , 4h ); 7 . 39 - 7 . 57 ( m , 5h ). 31 p - nmr ( d 2 o ; 162 mhz ): δ ( ppm ; h 3 po 4 = 0 )=− 12 . 4 ( br s , 1p ); − 13 . 3 ( br s , 1p ); − 24 . 9 ( br s , ip ). 3 ′- o - amino - thymidine - 5 ′- triphosphate . 3 ′- o -( fmoc ) amino - thymidine - 5 ′- triphosphate is dissolved in 20 % piperidine in dmf ( 0 . 5 ml ). the mixture is stirred at room temperature for 30 minutes and then concentrated in vacuo . the residue is redissolved in triethylammonium acetate buffer ( aqueous , 10 mm ; ph 7 ; 2 ml ) and purified by rp - hplc ( c 18 , gradient 0 - 21 % acetonitrile in 10 mm triethylammonium acetate over 27 minutes ) to give 3 ′- o - amino - thymidine - 5 ′- triphosphate as a colorless foam . the purity of the product is confirmed by analytical ion - exchange chromatography ( deae , gradient 0 - 1 m triethylammonium bicarbonate in water over 30 minutes ). 1 h - nmr ( d 2 o ; 300 mhz ): δ ( ppm )= 1 . 80 ( s , 3h ); 2 . 18 ( m , 1h ); 2 . 34 - 2 . 39 ( m , 1h ); 4 . 03 - 4 . 09 ( m , 2h ); 4 . 25 ( m , 1h ); 4 . 45 ( m , 1h ); 6 . 17 ( dd , j = 6 . 0 , 9 . 1 hz , 1h ); 7 . 66 ( s , 1h ). 31 p - nmr ( d 2 o ; 162 mhz ): δ ( ppm ; h 3 po 4 = 0 )=− 14 . 1 ( br s , ip ); − 16 . 3 ( br s , ip ); − 27 . 7 ( br s , 1p ). ms - esi − : [ m - h ] − calcd . for c 10 h 17 o 14 n 3 p 3 , 496 . 0 ; found , 496 . 4 . classically , fluorescent groups are appended to the 5 - position of pyrimidines , or the 7 - position of 7 - deaza purines . a variety of chemistry is available for preparing these classical derivatives ( see for example [ hob91 ]. work in the benner group ( see [ hel02 ] [ roy04 ] and references cited therein ) describe the “ two - part ” ( or perhaps better named , the “ two moving target ” optimization of polymerases and the 5 - position linker . tags at this position are accepted by polymerases [ hel02 ], and fluors at this positions are combined with modifications in the sugar to do dideoxy sequencing . disclosed here is one of several orthogonal protection strategies that allow for the attachment of the fluorescent tag onto the triphosphate without interference of the nucleophilic alkoxylamines ( fig8 ). other strategies are easily envisioned by those skilled in the art . the nucleosides bearing an iodo substituent at the 5 - position ( pyrimidines ) or 7 - position ( 7 - deazapurines ) are either commercially available or well documented in literature [ hob91 ]. first , the 3 ′- o - amino group is introduced by the procedure outlined above . next , the linker for the fluorophore or other tag is attached via a heck coupling reaction [ dey01 ]. the linker contains an olefin to allow the heck coupling to proceed , a base - labile boc protected n — o bond that is susceptible to cleavage by the naphthoquinone ( or its derivatives , or other reagents that cleave the n — o bond used to deblock the 3 ′- o group ), and a ( acid - labile protected ) primary amine for attachment of the fluorophore . the same linker is therefore used for all four nucleosides . the third step is the introduction of the triphosphate group , in analogy to the procedure outlined above . the boc protection of the linker amine is selectively removed by short treatment with trifluoroacetic acid , reportedly without cleaving either the triphosphate or the glycosidic bond [ sto99 ]. the attachment of the fluorophore to this amine via an activated ester is a broadly established procedure . final cleavage of the fmoc group yields the target compounds . the synthesis of the linker ( fig9 ) starts with dess - martin oxidation [ des91 ] of commercially available boc - aminoethanol to yield the corresponding aldehyde , which is captured with o - allylhydroxylamine to give the corresponding oxime . reduction with cyanoborohydride gives the amine which is protected with fmoc to give the target compound . several details are described below . oxime . tert - butyl n -( 2 - hydroxyethyl ) carbamate ( 900 mg ; 5 . 5 mmol ) is dissolved in anhydrous dichloromethane ( 40 ml ) at room temperature . dess - martin periodinane ( 2 . 12 g ; 5 . 0 mmol ) is added . the solution is stirred at room temperature for 2 h during which it turned into a milky suspension . aqueous nahco 3 / na 2 s 2 o 3 ( sat ., 40 ml ) is added and the mixture stirred for an additional 30 minutes . the organic phase is separated and the aqueous phase is extracted with dichloromethane ( 2 × 50 ml ). the combined organic phase is dried with brine ( 30 ml ) and na 2 so 4 and concentrated in vacuo , to give a yellow slime . the crude aldehyde is taken up in acetonitrile ( 30 ml ) and thf ( 20 ml ). o - allylhydroxylamine hydrochloride hydrate ( 720 mg ; ca . 6 . 5 mmol ) and potassium carbonate ( 900 mg ; 6 . 5 mmol ; powdered ) are added and the suspension is stirred at room temperature for 30 minutes . the solids are removed by filtration , and the filtrate is concentrated in vacuo . aqueous work - up ( dichloromethane ) and flash liquid chromatography ( silica ; eluent etoac / hexanes , 1 : 4 to 1 : 2 ) gives the oxime ( expected 670 mg ; 63 %) as a colorless oil which solidifies at − 20 ° c . 1 h - nmr ( cdcl 3 ; 300 mhz ): δ ( ppm )= 1 . 45 ( s , 9h ); 3 . 89 ( t , j = 5 . 0 hz , 1 . 2h ); 4 . 01 ( t , j = 4 . 9 hz , 0 . 8h ); 4 . 53 ( dt , j = 5 . 7 , 1 . 4 hz , 1 . 2h ); 4 . 58 ( dt , j = 5 . 7 , 1 . 4 hz , 0 . 8h ); 4 . 94 ( br s , 1h ); 5 . 19 - 5 . 33 ( m , 2h ); 5 . 90 - 6 . 04 ( m , 1h ); 6 . 74 ( t , j = 4 . 3 hz , 0 . 4h ); 7 . 44 ( t , j = 4 . 8 hz , 0 . 6h ). 13 c - nmr ( cdcl 3 ; 75 mhz ): δ ( ppm )= 28 . 6 , 36 . 8 , 40 . 0 , 75 . 0 , 75 . 3 , 80 . 1 , 117 . 8 , 118 . 2 , 134 . 1 , 134 . 3 , 146 . 8 , 149 . 9 , 155 . 8 . hrms - ei : [ mh + ] calcd for c 10 h 19 o 3 n 2 , 215 . 1396 ; found , 215 . 1486 . amine . the oxime ( 428 mg ; 2 mmol ) and methyl orange indicator ( ca . 1 mg ) are dissolved in methanol ( 10 ml ) at 0 ° c . a solution of methanolic hcl ( 6 n aqueous hcl : methanol , 1 : 1 ). a solution of sodium cyanoborohydride ( 150 mg ; 2 . 4 mmol ) in methanol ( 2 . 4 ml ) is slowly added as needed to maintain ph ≈ 3 . 5 and ice cold temperature . the final solution is stirred at 0 ° c . and ph 3 . 5 for an additional 30 minutes . the reaction is quenched by the addition of aq . nahco 3 ( sat ., 5 ml ) and aq . naoh ( 2 n , 200 μl ) and the methanol is removed in vacuo . aqueous work - up ( etoac ) and flash liquid chromatography ( silica ; eluent etoac / hexanes , 1 : 2 ) gives the amine ( expected 420 mg ; 97 %) as a colorless oil . 1 h - nmr ( cdcl 3 ; 300 mhz ): a ( ppm )= 1 . 45 ( s , 9h ); 2 . 99 - 3 . 04 ( m , 2h ); 3 . 27 - 3 . 33 ( m , 2h ); 4 . 18 ( dt , j = 5 . 9 , 1 . 3 hz , 2h ); 4 . 97 ( br s , 1h ); 5 . 18 - 5 . 32 ( m , 2h ); 5 . 71 ( br s , 1h ); 5 . 86 - 6 . 00 ( m , 1h ). 13 c - nmr ( cdcl 3 ; 75 mhz ): δ ( ppm )= 28 . 6 , 38 . 8 , 51 . 7 , 75 . 4 , 79 . 4 , 118 . 2 , 134 . 5 , 156 . 2 . hrms - ei : [ mh + ] calcd for c 10 h 21 o 3 n 2 , 217 . 1552 ; found , 217 . 1620 . final linker . the amine ( 216 mg ; 1 mmol ) is added to a solution of sodium carbonate ( 106 mg ; 1 mmol ) in water ( 2 . 5 ml ). fmoc - osucc ( 337 mg ; 1 mmol ) is dissolved in dioxane ( 2 . 5 ml ) and added . the mixture is stirred vigorously at room temperature for 2 h . the reaction is quenched by the addition of etoac ( 40 ml ) and aq . nacl ( 50 % sat ., 40 ml ). aqueous work - up and flash liquid chromatography ( silica ; eluent dichloromethane / methanol , 100 : 0 to 60 : 1 ) gives the target compound ( expected 130 mg ; 30 %) as a colorless oil . 1 h - nmr ( cdcl 3 ; 300 mhz ): a ( ppm )= 1 . 41 ( s , 9h ); 3 . 24 - 3 . 32 ( m , 2h ); 3 . 55 - 3 . 60 ( m , 2h ); 4 . 22 - 4 . 38 ( m , 3h ); 4 . 54 ( d , j = 6 . 4 hz , 2h ); 4 . 75 ( br s , 1h ); 5 . 22 - 5 . 32 ( m , 2h ); 5 . 81 - 5 . 95 ( m , 1h ), 7 . 28 - 7 . 43 ( m , 4h ); 7 . 60 - 7 . 63 ( m , 2h ); 7 . 74 - 7 . 78 ( m , 2h ). 13 c - nmr ( cdcl 3 ; 75 mhz ): δ ( ppm )= 28 . 6 , 38 . 7 , 47 . 4 , 49 . 8 , 67 . 8 , 76 . 2 , 79 . 6 , 120 . 2 , 120 . 4 , 125 . 2 , 127 . 4 , 128 . 0 , 132 . 3 , 141 . 6 , 143 . 9 , 156 . 0 , 157 . 6 . hrms - ei : [ mh + ] calcd for c 25 h 31 o 5 n 2 , 439 . 2233 ; found , 439 . 2244 . reverse transcriptase ( rt ) and a variety of dna polymerases of microbial origin are able to incorporate 3 ′- o - aminonucleoside triphosphates opposite their watson - crick pair in a complementary strand acting as a template for primed dna synthesis . reverse transcriptase is the ideal polymerase for direct sequencing of messenger rna . as rt also accepts dna templates , the enzyme can also be used in the sequencing - by - synthesis architectures being developed that amplify a small number of dna / rna molecules to give sequencable dnas ( in polonies , for example ). rt as well as other dna polymerases that accept 3 ′- o - aminonucleoside triphosphates are also useful for single molecule sequencing by synthesis strategies , if the 3 ′- o - aminonucleoside triphosphates carry a label that can be visualized at the single molecule level ( a fluorescent species such as rhodamine , cy3 and / or cy5 , a species that can be visualized by atomic force microscopy , or a species that can be visualized by stem , for example ). this notwithstanding , it is conceivable that mutant polymerases will be needed to accept to 3 ′- o - aminonucleoside triphosphates to meet the specifications of specific architectures . to obtain these , polymerases may be mutated , as has been done for other substrate analogs , guided by crystal structures for dna polymerases and reverse transcriptases [ eom96 ][ liy98 ][ kie98 ][ fra01 ][ hop99 ]. these crystal structures show a relatively tight packing between the enzyme and the 3 ′- hydroxyl group . as with the polymerases engineered to incorporate 2 ′, 3 ′- dideoxy nucleosides , the size of the amino acid residues in contact with the 3 ′- hydroxyl group is diminished . this disclosure teaches that replacing a phenylalanine in contact with the 3 ′- oh group by histidine , or a tyrosine in contact with the 3 ′- oh group by phenylalanine , improves the performance of polymerases for certain assay architectures . for site directed mutagenesis , the preferred protocol exploits the stratagene “ quik change ” kit . the process begins with a vector containing the inserted gene between strategically chosen restriction sites . this is transformed into an e . coli strain that is dam + . the colonies are grown , picked , and the subsequently extracting the plasmid with a miniprep or phenol - chloroform procedure . the vector is then used as a template for rolling circle replication where the primers bind to the desired mutation site on the gene of interest and introduce the desired mutation . both primers are designed to contain the desired mutation flanked by 15 nucleotides on each end , and the pcr is cycled for 18 rounds ( t denaturation : 30 sec ; t annealing : 60 sec . ; t extension : 1 min / kb plasmid ) with pfu turbo . the reaction is then treated with the dpni restriction nuclease to degrade the methylated and hemi - methylated dna of the original plasmid , thus leaving only the mutated dna produced in the pcr . the nicked product from the rolling circle replication is then transferred into a carrier cell line xl - 21 blue ( stratagene ). this method gives an 80 % mutation rate , making isolation of the correct variant trivial it is possible that rationally designed mutants of some ( or all ) of these polymerases may well prove to accept 3 ′- o - amino - 2 ′- deoxyribonucleoside triphosphates with the high rate and fidelity that meets the specifications for the sequencing - by - synthesis strategy . if this is the case , then work to develop polymerases will be done . recognizing that most site - directed mutagenesis is in fact site - directed damage , however , an alternative approach for obtaining polymerases that incorporate 3 ′- o - amino - 2 ′- deoxyribonucleoside triphosphates to specifications is preferred . this exploits a strategy , called compartmentalized self - replication ( csr ), for the evolution of polymerases [ gha01 ]. in csr , individual polymerase variants are isolated in water droplets that are suspended in oil . these droplets provide separate compartments into which are put single e . coli cells containing a clone for a single polymerase variants , together with nucleoside triphosphates and other appropriate reagents . within the drop , each polymerase replicates only its own encoding gene to the exclusion of genes in other compartments . consequently , only genes encoding active polymerases are manipulated , while inactive variants fail to amplify their own genes and disappear from the gene pool . among differentially active variants , the more active can be expected to produce proportionally more “ offspring ,” correlating post replication copy number with enzymatic turnover . as was shown in earlier work by tawfik and griffiths [ taw98 ], the individual drops in a water - in - oil emulsion are stable for prolonged periods at temperatures exceeding 90 ° c . this approach allows selection for enzymatic activity under a wide range of conditions . using this approach , holliger selected for variants of the taq dna polymerase with 11 - fold higher thermostability than the wild - type enzyme or with a & gt ; 130 - fold increased resistance to the inhibition by heparin [ gha01 ]. selection for a polymerase that incorporates 3 ′- o - amino - 2 ′- deoxynucleotides is done using this system with some minor adaptations . as with holliger &# 39 ; s experiment , the polymerase variants are carried on a pask75 plasmid . the gene lies after an xbai site and before a sali site ( c * aattg ) and a tli site ( c * tcgag ) site . the expression of the polymerase variant is done inside the cell . the solution outside the cell , however , contains tli endonuclease , a thermostable restriction enzyme , as well as a 3 ′- o - amino - 2 ′- deoxynucleoside triphosphate . in the first heat cycle , the cell breaks open and the plasmid is delivered to the restriction endonuclease outside the cell . the restriction enzyme cleaves the plasmid at the single tli site , generating a sticky end with a 3 ′- overhang that can serve as a polymerization template . the thermostable polymerase variant released from the cell then has the opportunity to add a single 3 ′- o - amino - 2 ′- deoxynucleotide to the 3 ′- end of the sticky end in a template - directed fashion . polymerases that can do so will tag their own gene with a 3 ′- onh 2 unit . work up of the emulsion in ether / water mixtures generates a pool of dna that encodes variants of taq . those variants that were able to add a 3 ′- o - amino - 2 ′- deoxynucleotide will be tagged with a 3 ′- onh 2 unit . these will be retained on an aldehyde column through the formation of an oxime . those that failed to add a 3 ′- onh 2 unit will be washed from the column , as the only other amine groups in the dna structure ( the exocyclic nucleobase amines ) are shielded from reaction by hydrogen bonding interactions and the phosphodiester backbone . due of the presence of a sali site between the gene and the 3 ′- o - amino - 2 ′- deoxynucleotide , the 3 ′- cap can be cleaved with sali , the encoding region of the gene can be recovered by cleaving with xbai . the genes are then shotgun cloned back into the plasmid between the xbai and sali sites , ready for another cycle of selection or for analysis . the tli site is especially convenient , as it creates a sticky end having one of each of the four nucleotides . if the 3 ′- o - amino - 2 ′- deoxynucleoside bears a thymine , then termination occurs at the first nucleotide , and one selects for polymerases that incorporate a t - bearing 3 ′- o - amino - 2 ′- deoxynucleoside opposite a . to select for polymerases that incorporate 3 ′- o - amino - 2 ′- deoxynucleotides bearing c , we add this triphosphate as well as dttp . the polymerase will add the first ( natural ) da , and then will be challenged to complement the next nucleotide in the template ( a g ). this process can be completed to screen for polymerases that incorporate all nucleotides . conversely , the procedure is reversed to exclude polymerases that incorporate the wrong nucleotide . thus , the first cycle can include the 3 ′- o - amino - 2 ′- deoxynucleoside triphosphate carrying a c . a faithful polymerase will not incorporate it opposite the first a in the template . here , the affinity column cycle is reversed , where the undesired genes are retained on the column , and the desired genes are eluted . these water - in - oil emulsions are simple to make . briefly , 0 . 2 ml of csr mix [ the required 3 ′- o - amino - 2 ′- deoxynucleoside triphosphate and any required dntp &# 39 ; s ( 0 . 2 mm for taq , 0 . 8 mm for vent and 9 ° n variants ), 50 μm tetramethylammonium chloride , and 0 . 05 % ( vol / vol ) dnase - free pancreatic rnase ( roche ) in 1 × taq buffer , as well as the tli enzyme and induced taq expresser cells ) are added drop wise to 0 . 4 ml of the organic phase [ 4 . 5 % ( vol / vol ) span 80 ( fluka ), 0 . 4 % ( vol / vol ) tween 80 , and 0 . 05 % ( vol / vol ) triton x - 100 in light mineral oil ( all sigma )] under constant stirring ( 1 , 000 rpm ). after addition of the aqueous phase , stirring is continued for 5 minutes more before thermocycling . compartment dimensions are determined by light microscopy and by laser diffraction spectroscopy . compartments had average diameters of 15 μm and proved heat - stable , with no coalescence or changes in compartment size after 20 cycles of pcr as judged by laser diffraction and light microscopy . for recovering polymerase genes , emulsions are quenched with ether and the phases are separated . the aqueous phase was extracted with ether , and the dna mixture is passed through an aldehyde affinity column and washed thoroughly . the captured dna is then removed either by washing with acetone - water mixtures , or by direct cleavage with sali . a working prototype for a sequencing by synthesis is built on a glass slide that uses dna molecules that are mobilized in the form of a hairpin , and are therefore able to self - prime . the slide is dipped into a solution containing the four 3 ′- o - amino - 2 ′- deoxynucleoside triphosphates and the polymerase . one fluorescently labeled , capped nucleotide is incorporated on each spot , selected to be the one that is complementary to the next nucleotide on the template . the excess reagents are removed by washing , and a four color fluorescence imager is used to image the surface of the chip . the color of each spot reveals the identity of the nucleotide that was added . after imaging , any unreacted 3 ′- oh groups on the self - primed template are capped by adding ddntps and dna polymerase . the 3 ′- oh cap and the fluorescent label are then removed by adding a solution containing the napthoquinone reagent , and the chip is washed again . the process is repeated . a fluorimeter that is equipped with an accessory to detect fluorescence from a glass slide is used to image the fluorescence emission in our proposed dna sequencing system . for large scale tests , a multi - color scanning system able to detect four different fluorescent dyes ( 500 nm - 700 nm ) ( gsi lumonics scanarray 5000 standard biochip scanning system ) is used . for both proof - of - concept and more advanced work , two - dimensional arrays of hairpin dna are used . these synthetic templates for evaluating the technique of sequencing by synthesis are immobilized on 96 - well plates with well coated with streptavidin . biotin attachment strategies are preferably replaced by a covalent immobilization chemistry . such chemistry provides the chip with greater stability and a longer shelf life ( fig1 ). 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referring initially to fig1 , a syringe device for expelling a fluid through a needle mounted on a hub is shown and generally designated 10 . as shown in fig1 , the device 10 includes a substantially cylindrical syringe body 12 that is centered on an axis 14 and formed with a finger grip 16 at its proximal end . fig1 further shows that the device 10 includes an adapter 18 sized to fit within the syringe body 12 . the adapter 18 includes a cylindrical portion that is also centered on the axis 14 . for the device 10 , a substantially cylindrical needle guard 20 is provided and positioned co - axially with both the syringe body 12 and adapter 18 . the guard 20 is sized to fit within the adapter 18 . it can be further seen that the device 10 includes a plunger 22 that is formed with a grip flange 24 at its proximal end . referring to fig2 , a straight , elongated hypodermic needle 26 is shown extending from a sharp needle tip 28 to a needle hub 30 . as best seen in fig3 a , the needle 26 may be mounted to the passively guarded , fillable injection device 10 . specifically , the device 10 includes a luer member 32 that receives and engages the needle hub 30 . the luer member 32 has a proximal portion or head 34 . extending distally from the head 34 is a substantially cylindrical shaft 36 centered on the axis 14 . the needle hub 30 is mounted to the luer member 32 at the shaft &# 39 ; s distal portion or distal shaft end 38 . additionally , the head 34 has a proximal side 33 and a distal side 35 that engages the adapter 18 . circumferentially - spaced truss - like webs 40 are provided on the luer member 32 to reinforce the connection between the shaft 36 and the head 34 . furthermore , the luer member 32 includes a pipe - like conduit 39 that extends from the proximal side 33 of the head 34 to the shaft end 38 . when the needle hub 30 is frictionally mounted on the shaft end 38 , the needle hub 30 and luer member 32 are sealed together to establish fluid communication between the needle 26 and the conduit 39 . as shown in fig3 a , the adapter 18 engages the luer member 32 about the webs 40 thereby preventing rotational movement therebetween . the adapter 18 includes a substantially cylindrical wall 42 that is centered on the axis 14 and forms a cavity 43 . the wall 42 extends from a proximal end 44 substantially covered by a base 45 to an open distal end 46 . at its proximal end 44 , the adapter 18 has a narrow circumference and is designed to engage the distal side 35 of the head 34 of the luer member 32 . at its distal end 46 , the adapter 18 has a broad circumference and is designed to engage the plunger 22 and receive the guard 20 . as can be seen in fig3 a , the adapter 18 also includes two oppositely positioned , axially aligned slits 48 . as best seen in fig3 a , the adapter 18 is sized to allow the cylindrical guard 20 to move along the axis 14 into and out of the adapter cavity 43 . specifically , the guard 20 may be moved between an extended position 49 ( shown in fig3 a and 4a ) to a retracted position 53 ( shown in fig3 b and 4b ). structurally , the guard 20 is a shell forming a lumen 51 that extends between an open proximal end 50 and an open distal end 52 . the guard 20 includes abutments 54 that extend radially outward from the proximal end 50 . also in fig3 a , it can be seen that the inverted plunger 22 has a substantially cylindrical side member 56 that extends from a closed proximal plate member 58 to an open distal edge 60 . structurally , the cylindrical side member 56 surrounds a fluid chamber 62 and is slidingly mounted on the proximal end 44 of the adapter 18 . fig3 a further shows that the plunger 22 is formed with tangs 64 that extend radially inward ( i . e . toward the axis 14 ) and distally from the cylindrical side member 56 of the plunger 22 . it can be seen in fig3 a , that the device 10 includes an elastomeric seal 66 that is attached onto the proximal end 34 of the luer member 32 . specifically , the seal 66 is press fitted onto the proximal end 34 of the luer member 32 . as shown , the seal 66 has a generally fusiform or spindle - like shape and is formed with a through - hole 68 . when the open distal edge 60 of the plunger 22 is slid over the luer member 32 and adapter 18 , the seal 66 compresses between the luer member 32 and the cylindrical side member 56 of the plunger 22 to establish sealed fluid communication between the fluid chamber 62 and the conduit 39 of the luer member 32 . when the needle hub 30 is mounted on the luer member 32 to establish fluid communication between the needle 26 and the conduit 39 , the plunger 22 can be moved to a withdrawn position 61 ( shown in fig3 b and 4b ) to draw fluid through the needle 26 and into the chamber 62 . furthermore , the plunger 22 can be moved to an advanced position 63 ( shown in fig3 c and 4c ) to expel fluid from the chamber 62 through the needle tip 28 . as further shown in fig3 a , the syringe body 12 extends from an open proximal end 70 to an open distal end 71 . positioned at the proximal end 70 , the finger grip 16 includes a recess 72 sized to receive the grip flange 24 of the plunger 22 . functionally , the plunger 22 can be advanced distally after an injection until the grip flange 24 is positioned in the recess 72 . once the grip flange 24 is positioned in the recess 72 it cannot be removed ; therefore , subsequent movement of the plunger 22 relative to the syringe body 12 is effectively prevented . turning to fig4 a , other features of the device 10 may be seen . specifically , the adapter 18 is shown having cam levers 74 positioned at its distal end 46 . the cam levers 74 are in a biased position 76 in which the plunger 22 forces them to be coincident with the rest of the cylindrical wall 42 . however , the cam levers 74 mechanically prefer a relaxed position 78 ( shown in fig4 b ) in which the distal ends 80 of the cam lever 74 extend radially outward from the cylindrical wall 42 . as shown in fig4 a , the guard 20 has hinges 82 . similar to the cam levers 74 of the adapter 18 , the hinges 82 of the guard 20 have a relaxed position 84 in which the proximal ends 86 of the hinges 82 extend radially outward from the rest of the guard 20 . the biased position 88 of the hinges 82 is shown in fig4 b . as further shown in fig4 a , the syringe body 12 can also include flanges 90 at its distal end 71 . the flanges 90 extend distally and radially inward from the cylindrical portion 92 of the syringe body 12 . their purpose is discussed below . by cross - referencing fig3 a - d and 4 a - d , it can be seen that the device 10 includes a mechanism to lock the guard 20 in an extended position 49 covering the needle tip 28 prior to an injection procedure . once locked , the guard 20 can only be unlocked by movement of the plunger 22 . as previously discussed , the adapter 18 is formed with cam levers 74 having distal lever ends 80 . comparing fig4 a with fig4 b , it can be seen that the cam levers 74 are deflectable by the cylindrical side member 56 of the plunger 22 from a relaxed position 78 ( fig4 b ) to a biased position 76 ( fig4 a ). in the relaxed position 78 ( fig4 b ), the cam levers 74 extend radially outward from the remaining cylindrical section of the adapter 18 . on the other hand , as shown in fig3 a , in the biased ( i . e . deflected ) position 76 , the cam levers 74 are coincident with the remaining cylindrical wall 42 of the adapter 18 . when the plunger 22 is in the advanced position 63 shown in fig4 a , the cylindrical side member 56 of the plunger 22 contacts the cam levers 74 and deflects them into the biased position 76 . as shown in fig4 a , when the cam levers 74 are in the biased position 76 , the lever ends 80 engage the proximal ends 86 of the hinges 82 of the guard 20 and prevents proximal movement of the guard 20 . when the plunger 22 is in its withdrawn position 61 as shown in fig3 b and 4b , the cam lever 74 relaxes into its undeflected , outward position 78 ( as shown in fig4 b ) and allows the guard 20 to move proximally . as an additional locking mechanism , the syringe body 12 may be moved relative to the adapter 18 to deflect the cam levers 74 of the adapter 18 with its flanges 90 . as shown in fig4 d , the flanges 90 are moved toward the adapter 18 when the plunger 22 and adapter 18 are fully pushed into the syringe body 12 . as a result , the flanges 90 contact and force the cam levers 74 of the adapter 18 to the biased position 76 to lock the device 10 to prevent any further proximal movement of the needle guard 20 . this prevents inadvertent reuse of the device 10 . initially , the device 10 is provided without a needle 26 . to mount a needle 26 on the device 10 , the needle guard 20 is first moved to the retracted position 53 by withdrawing the plunger 22 . then the needle hub 30 is frictionally engaged with the shaft end 38 of the luer member 32 as can be understood from fig3 b and 4b . after mounting the needle hub 30 on the shaft end 38 , the needle guard 20 is allowed to move to its extended position 49 to cover the needle 26 by moving the plunger 22 to its advanced position 63 as shown in fig3 a . as further shown in fig3 a the tangs 64 of the plunger 22 extend through the slits 48 in the adapter 18 to engage the abutments 54 and retract the guard 20 when the plunger 22 is withdrawn . from fig4 a , it can be seen that the cylindrical side member 56 of the plunger 22 holds the cam levers 74 deflected inward to lock the guard 20 and prevent proximal movement of the guard 20 . as illustrated by fig3 a - b and 4 a - b , use of the device 10 begins by withdrawing the plunger 22 . such proximal movement of the plunger 22 has several effects . specifically , as shown in fig4 a and 4b , initial proximal movement of the plunger 22 allows the cam levers 74 to relax outwardly from the axis 14 and unlock the guard 20 for proximal movement . as shown in fig3 a and 3b , additional proximal movement of the plunger 22 engages the tangs 64 with the abutments 54 , causing the guard 20 to be retracted with the plunger 22 . also , withdrawal of the plunger 22 draws air ( or other fluid ) through the needle 26 and into the fluid chamber 62 . once the guard 20 has been retracted as shown in fig3 b and 48 , the next step is to insert the exposed distal needle tip 28 into a medicament vial ( illustrated by surface 94 in fig3 c and 4c ). at this point , the plunger 22 can be depressed as shown in fig3 c and 4c to expel air into the vial and void the fluid chamber 62 . comparing fig3 b and 4b with fig3 c and 4c , it can be seen that during its advance the plunger 22 disengages the guard 20 . thus , as illustrated by fig3 c and 4c , after advancing the plunger 22 , distal movement of the guard 20 is only prevented by the contact between the distal end 52 of the guard 20 and the surface 94 . next , the plunger 22 can be withdrawn to fill the chamber 62 with medicament fluid 95 ( note fig3 b and 4b are representative of the configuration of the device 10 after the chamber 62 is filled with medicament 95 ). from fig3 b , it can be seen that during withdrawal of the plunger 22 , the tangs 64 reengage the abutments 54 . the result is that the plunger 22 engages the guard 20 and prevents distal advancement of the guard 20 . as illustrated by fig3 b and 4b , when the needle 26 is removed from the vial , the distal tip 28 of the needle 26 remains unguarded and exposed . the device 10 is now ready for an injection . as illustrated by fig3 c and 4c , to inject a medicament into a patient , the distal tip 28 of the needle 26 is inserted into the patient ( represented by surface 94 ) and the plunger 22 is depressed . as shown in fig3 c , the distal advancement of the plunger 22 releases the guard 20 . once released , the guard 20 is free to move distally under the influence of a coil spring 96 that is interposed between the guard 20 and the adapter 18 . thus , as the needle 26 is withdrawn from the patient , the needle 26 retracts proximally into the guard 20 which remains in contact with the patient &# 39 ; s skin ( represented by surface 94 ). fig3 a and 4a are representative of the device 10 after the needle 26 has been withdrawn from the patient and the needle 26 has passively retracted into the guard 20 . once the device 10 has been removed from the patient , the plunger 22 and the adapter 18 can be advanced distally relative to the syringe body 12 to lock the guard 20 in place ( fig4 d ). fig3 d and 4d also show that this places the grip flange 24 of the plunger 22 in the recess 72 formed in the syringe body 12 . functionally , once the device 10 is in the configuration shown in fig3 d and 4d , the plunger 22 is disabled and the guard 20 completely covers the hollow needle 26 to protect the user from unwanted needle sticks and prevents inadvertent reuse of the device 10 . while the particular devices and methods as herein shown and disclosed in detail are fully capable of obtaining the objects and providing the advantages herein before stated , it is to be understood that they are merely illustrative of the presently preferred embodiments of the invention and that no limitations are intended to the details of construction or design herein shown other than as described in the appended claims .	0
fig1 shows a settling tank 1 of the present invention in an assembled configuration . the constituent components are best shown in the exploded view of fig2 . the portable settling tank 1 is comprised of a portable open - top container 40 , a disposable watertight liner 3 , a disposable coarse granular material 10 , a disposable filter cloth 20 , and a drain port 2 . the cross - section view of fig4 shows how the components are layered and overlapped to form a vessel for receiving a thin slurry 30 . the slurry 30 , comprised of particulate 32 ( not shown ) suspended in water , is introduced by pump action into the vessel through a deeply - drafted inlet port 5 . the particulate 32 settles therein by gravity segmentation to leave a floating layer of substantially clean water 31 . filtration through the filter cloth 20 into an interstitial space 14 in the coarse granular material 10 results in a filtrate 22 ( not shown ), which is also substantially void of particulate 32 . filtrate 22 is removed by pump or gravity action through the drain port 2 . clean water 31 is removed by pump action through a shallowly - drafted exit outlet port 6 . the resulting residue , consisting essentially of dewatered particulate 32 , is discarded along with all contents of the vessel , including the watertight liner 3 , the coarse granular material 10 , and the filter cloth 20 . the watertight liner 3 assures that the open - top container 40 is left in its original state and precludes any need for cleaning or decontamination . referring to fig2 , portable open - top container 40 has a bottom 41 and four sides 42 enclosing a volume . the volume may be of any size appropriate for the amount of slurry to be processed . in the preferred embodiment , the volume is defined by the dimensions is of 22 feet long by eight feet wide by four and a half feet deep . while any portable rigid or semi - rigid container is suitable , preferably the open - top container 40 is a roll - on waste container 43 , typically available by rental from a local waste - disposal company . because the open - top container 40 is portable , a transportation means for hauling purposes is also comprehended . the watertight liner 3 is draped over the bottom 41 and four sides 42 of the open - top container 40 to shield the interior surfaces of the container . the watertight liner 3 may lap over the top edges of the container , or otherwise be fixed thereto , so that the liner cannot be caused to expose the interior surfaces . the watertight liner 3 is preferably a film with a gauge of 5 - 10 mils . while any waterproof film is suitable , a preferred choice would be one of bio - degradable or recycled resin composition , in order of preference . the preferred resins are those comprising polyethylene , polypropylene , or a mixture thereof , or polyolefin , which may be a blend of those resins . a layer of coarse granular material 10 is laid over the bottom of the watertight liner 3 to effectively provide a reservoir for drainage by means of interstitial space 14 . interstitial space 14 is comprised of all space within the boundaries of the layer which is not filled with the material of the coarse granular material 10 . preferably , the layer is 6 - 12 inches in depth , but may be any depth consistent with the volume of drainage desired . the coarser the consistency , the larger the interstitial space 14 for a given volume of the layer ; consequently , therefore , coarsening provides a means for optimization . the coarse granular material 10 may be anything disposable which has the property of maintaining is interstitial space therein , as , for example , pine cones , or discarded bricks arrayed in a jumble . it may also be discarded old pallets , or broken up construction materials , although not granular in the same sense . in the preferred embodiment , the coarse granular material 10 is stones 11 , and in a particularly preferred embodiment , the stones are river rock 12 . the drain port 10 vents the watertight liner 3 and ducts into the interstitial space 14 to drain said space . in the preferred embodiment , an intermittent pump provides the means for draining . the intermittent pump should be of a peristaltic , or otherwise of a self - priming , type because the pump may outstrip the flow of drainage . in an alternate embodiment , shown in fig3 , gravity may provide the means for draining . in order to facilitate this means , a side opening 44 is provided in at least one of the sides 42 to permit a gravity flow there through . in a particular alternate embodiment , the side opening 44 is a doorway 45 , which may otherwise provide access to the interior of open - top container 40 . if there is a door 47 in the doorway 45 , and if there are gaps around the periphery thereof , the gaps may present sufficient opening for leaching purposes . otherwise , a false wall 46 may be constructed adjacent to the doorway 45 to function as a supporting wall and prevent collapse of the vessel when door 47 is positioned open . false wall 46 may have an aperture 48 , which is in fluid communication with the drain port 2 , to facilitate gravity drainage . false wall 46 may be guyed to one or more sides 42 by rope or cabling to thereby support it upright . it is intended that false wall 46 be discarded with the contents of the open - top container 40 . false wall 46 may be comprised , for example , of an old sheet of plywood . the disposable filter cloth 20 is draped over the watertight liner 3 and the layer of coarse granular material 10 . the filter cloth 20 may lap over the top edges of the container , or otherwise be fixed proximate thereto , so that the filter cloth remains at all times above the liquid surface level . the filter cloth 20 is a woven or nonwoven textile having a sieve matched to the tiniest allowable particle in the filtrate . in the preferred embodiment , the filter cloth 20 is a geotextile cloth , or equivalent , fabricated with polyester or polypropylene yarns , or , otherwise laid up with polypropylene fibers . such a material is sometimes used in road construction or for environmental stabilization . the preferred sieve size is in the 100 - 200 micron range , and a particular preference requires 150 microns or less to trap seeds . the filter cloth 20 is designed to substantially trap the particulate 32 and separate it from the filtrate 22 by filtering action . this filtering action may or may not be assisted by pump suction through the drain port 2 . applying pump suction before the particulate 32 has had a chance to naturally settle , however , might clog the filter cloth 20 prematurely by driving particles into the pores of the cloth . in a similar way , slurry maintained at full tank capacity , or in other words , with a full “ head ”, would hydraulically pressurize the sediment layer on the bottom . a means for reducing water in the slurry while substantially avoiding clogging of the filter cloth 50 ( fig5 ), hereinafter “ a means for reducing water 50 ”, therefore , would comprise the procedural steps of adding the slurry 30 and pumping the clean water 31 in staggered cycles that would result in minimizing the head . a staggered cycle would involve , for example , pumping in slurry , waiting for is settlement to vacate a thin top layer , and then pumping clean water out of the thin top layer . the means for reducing water 50 would further comprise cyclically pumping the filtrate 22 to maintain the filtrate level just above the bottom of the filter cloth 20 ; or , otherwise , allowing gravity drainage of the filtrate 22 . these cyclical steps of pumping , both of clean water and of filtrate , if applicable , would continue until a preferred buildup of settled particulate 33 ( not shown ) is achieved . it is recognized that the stratification of particulate 32 within the pool of slurry 30 is in the form of a gradient , rather than discrete in the form of layers . that is to say , there is a distribution of particulate 32 decreasing from bottom to top over any relatively short period of time , such that a “ clean ” top layer is only an approximation . it is further recognized that the addition of more slurry 30 will inevitably disturb this distribution . the preferred means for reducing water 50 , therefore , further comprises pumping in slurry at one end of the open - top container 40 and pumping out clean water at the opposite end . the preferred means still further comprises locating the distal end of the inlet port 5 at or near the top of the bottom settlement and the distal end of the outlet port 6 at or near the top of the clean water layer . as the bottom settlement collects over time and rises in level , the distribution will cause more and more of the particulate 32 to remain present in the clean water layer . when a recognizable amount of particulate is pumped out with the clean water , it is either a signal that the current pumping cycle is excessive ; or , otherwise , that the preferred buildup of settled particulate 33 has been reached . the latter will be hallmarked by shorter and shorter pumping cycles . an amount of particulate 32 in the clean water 31 which is recognizable might be that is amount clogging a filter to the pump , for example . when the preferred buildup of settled particulate 33 has been reached , the pumping of filtrate 22 may proceed unrestricted until all water is substantially removed and an essentially dry residue remains . fig5 shows an alternate embodiment , wherein a method for dewatering a slurry 100 comprises the following process : step 101 . providing the portable open - top container 40 having the bottom 41 and four sides 42 . step 102 : covering the bottom 41 and the four sides 42 with the disposable watertight liner 3 . step 103 : covering the bottom of the watertight liner 3 with the coarse granular material 10 having the interstitial space 14 therein . step 104 : layering the filter cloth 20 over the coarse granular material 10 and the watertight liner 3 . step 105 : providing the drain port 2 through the watertight liner 3 and into the interstitial space 14 . step 106 : pumping the slurry 30 containing the particulate 32 into one end of the open - top container 40 through the open top , whereby settlement produces relatively clean water 31 at the top of container and settled particulate at the bottom , and filtering through the filter cloth 20 produces the filtrate 22 in the interstitial space 14 . step 107 : using the means for reducing water 50 , whereby room is provided for the cyclical addition of more slurry 30 . step 108 : deciding whether or not the preferred buildup of settled particulate 33 has been achieved ; and , if not , repeating steps 106 and 107 . step 109 : draining any remaining filtrate 22 through the drain port 2 . step 110 : transporting the open - top container 40 and its residual contents to a disposal site . step 111 : discarding the watertight liner 3 , the coarse granular material 10 , the filter cloth 20 and the residue by dumping the contents to leave the container in its original state . it is to be understood that the invention is not limited in its application to the details of construction and to the arrangements of the components set forth in the preceding description or illustrated in the drawings . the means for reducing water 50 might be carried out by evaporation in place of pumping clean water , for example . 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 .	1
the present invention relates to an apparatus and method for the treatment of stimulation fluid . when describing the present invention , all terms not defined herein have their common art - recognized meanings . to the extent that the following description is of a specific embodiment or a particular use of the invention , it is intended to be illustrative only , and not limiting of the claimed invention . the following description is intended to cover all alternatives , modifications and equivalents that are included in the spirit and scope of the invention , as defined in the appended claims . fig1 illustrates a schematic depiction of one embodiment of the present invention . the treatment of the stimulation fluid is carried out in a tank ( 1 ) having a first end ( 30 ) and a second end ( 32 ) and that is sectioned . as shown in fig1 , in a preferred embodiment , the tank ( 1 ) has three sections , a primary agitation section ( 2 ) into which the stimulation fluid is initially charged through the fluid inlet ( 25 ), an intermediate settling section ( 3 ) and a final settling section ( 4 ). however the tank ( 1 ) may have any number of intermediate sections to optimize the process as required . the final settling section ( 4 ) has a fluid outlet ( 6 ) for the removal of treated fluid . the sections are separated by substantially vertical barriers ( 22 ) that extend from the floor of the tank ( 26 ) upwards towards the roof of the tank ( 27 ). the transfer of fluid from one section to another occurs by primarily or solely by flowing over the top of the barriers ( 22 ) when the level of the fluid in the section reaches the level of the top of the vertical barrier ( 22 ). solids and denser fluids remain trapped behind the barrier while lighter fluids forming the upper layers pass over the barrier . as the stimulation fluid is pumped into the tank ( 1 ) through the fluid inlet ( 25 ), reagents including , but not limited to , liquefied clay and acidified water are added from separate storage vessels ( 10 , 11 ). the mixture of reagents and stimulation fluid enters the tank through the fluid inlet ( 25 ) and fluid flows in a direction from the first end of the tank ( 30 ) towards the second end of the tank ( 32 ). as more of the stimulation fluid and reagent mixture is added , any reagent , such as clay or aqueous acid and having a density greater than the density of the stimulation fluid settles to the bottom of each section , while the lighter hydrocarbon - based stimulation fluid forms an upper layer . some of the heavier density reagent may overflow into the intermediate ( 3 ) or final settling section ( 4 ); however , the amount settling in the bottom of the sections decreases in going from the primary ( 2 ) to the final section ( 4 ). the primary agitation section ( 2 ) may be provided with a baffle ( 24 ) to direct the flow of the mixture of stimulation fluid and reagent mixture downwardly towards the floor of the tank ( 26 ). as more of the mixture is added and is agitated by re - circulation ( as described below ) in the primary agitation section ( 2 ), the primary section ( 2 ) becomes filled and the stimulation fluid and some reagent and entrained solids may overflow into the adjacent intermediate section ( 3 ). operation in this manner continues until the level of fluid in the intermediate section ( 3 ) reaches a level whereby it spills over into the final settling section ( 4 ). as shown in fig1 , in one embodiment , the tank further comprises a fluid agitation system that can be coupled to the primary agitation section ( 2 ), or to any of the other sections to promote the mixing of the reagents and the stimulation fluid . in this manner , the lower phases of a section may be selectively removed and mixed and agitated and then reintroduced to the primary section ( 2 ) through the fluid inlet ( 25 ). the system consists of a loop containing a mixing pump ( 8 ) and optionally a jet mixer ( 14 ) as well . fluid is extracted from the bottom of the sections through a section outlet ( 34 ) positioned at the lowest point of the floor of each section . the extracted fluid is mixed and agitated using the mixing pump ( 8 ) and then reintroduced to the tank ( 1 ) through the fluid inlet ( 25 ). the jet mixer ( 14 ) may be additionally used to introduce powdered additives such as clay . agitation in this manner promotes thorough and complete mixing of the reagents and the stimulation fluid . agitation in the primary and intermediate sections may also be achieved using such other suitable agitation means as would be selected by one skilled in the art including use of a mechanical agitator ( not shown in the figures ) and baffles ( not shown in the figures ). the sections of the tank are connected such that they share a common vapour space towards the roof of the tank ( 27 ). the tank ( 1 ) has a vapour outlet ( 36 ) to facilitate the removal of vapor build up . in one embodiment , a vapour transfer line having an associated pump ( 5 ) is coupled to the vapour outlet ( 36 ) for the avoidance of pressure build - up . in one embodiment , after the stimulation fluid and regent mixture has been thoroughly mixed for sufficient amount of time in a section , the entire section containing the reagent - fluid mixture may be transferred to the next section , analogous to a batch process , or alternatively , the operation can be carried out as a continuous process , where portions of a section are transferred to the adjacent section and so on . the intermediate and final settling sections allow for separation of the hydrocarbon phase from the aqueous phase in the case of acid treatment , or separation of the hydrocarbon phase from the settling agent for removal of the gelling agent . complete separation is not necessarily required and may be monitored by means of a sight - tube ( not shown ) or the like . any of the sections may include a sloping floor to assist in collection and removal of solids , or denser fluids . in one embodiment , each of the sections comprises a floor which slopes upwards towards the second end of the tank ( 32 ), as shown in fig1 . as already discussed , a section outlet ( 34 ) is situated in a lower portion of each section . in one embodiment the section outlet ( 36 ) comprises a collection tube placed transversely within each section , at the bottom of the sloping floor . the section outlets ( 36 ) may be attached to a suction manifold ( 7 ) as described below . a fluid outlet ( 6 ) is connected to the final settling section ( 4 ) for removal of the treated stimulation fluid and , transfer and storage to a product return vessel or barrel ( 16 ) assisted by a product return pump ( 9 ). the sections outlets ( 36 ) are also connected to a tank suction manifold ( 7 ) via appropriate valves . at one end , the tank suction manifold ( 7 ) is connected to a suction point for a vacuum truck ( 15 ) that may be used to clean out the unit when operations has been completed or to change chemicals during operation , and at the other end to the previously described agitation and mixing system . the tank suction manifold ( 7 ) allows for recirculation of the stimulation fluid and more complete treatment of the fluid , which may be tested using appropriate sensors within each section . in one embodiment , the primary agitation section ( 2 ) has a volume approximately one - half of the intermediate settling section ( 3 ) and a final settling section ( 4 ), which may have approximately equal volume . relative residence time in each section may be manipulated by providing different volume capacity in each section , or by varying the height of the barriers ( 22 ) which separate the sections , or both . overall residence time in the tank ( 1 ) may be varied by altering the flow rate into the fluid inlet ( 25 ). fig1 also discloses a heat exchange system ( 13 ) with appropriate connections , valves , pumps and controls connected to two fluid storage vessels ( 12 and 16 ). the fluid storage vessels ( 12 and 16 ) may be used to store untreated stimulation fluid and to receive treated fluid from the fluid outlet ( 6 ). the heat exchange system ( 13 ) is used to preheat the stimulation fluid prior to introduction to the tank ( 1 ) which promotes reactivity with the reagents . various modifications can be made to the heat exchange system without departing from the scope of the invention . in addition , although glycol has been indicated as the fluid for heat exchange , a skilled artisan would recognize that other fluids have heat exchange capacity , such as , for example , thermaoil ™, dowtherm ™ or silitherm ™ can also be used , where appropriate . the setup disclosed in fig1 has a common pathway , which is preferred but not essential , for the two fluid storage vessels ( 12 , 16 ) for receiving and heating the fluid . the outlet from the heat exchanger is set up so that the product may be returned to the originating vessel or can be used to transfer the fluid from one product vessel to another . in addition , appropriate connections and valves have been provided to re - direct the stimulation fluid from either storage vessel ( 12 , 16 ) for treatment to the inlet on the tank ( 1 ). the size of the apparatus for treatment of the fluid can vary depending upon the objective for use of it , as would be known to a skilled artisan . in addition , the apparatus can be setup near a site of operation or can be mounted and operated on a moving vehicle , as shown in fig2 - 6 , or may be skid - mounted . fig2 - 6 disclose an embodiment with additional intermediate settling sections , which may be added as required , for optimization of the process . various other modifications and amendments may be made to the apparatus disclosed and discussed herein , without departing from the scope of the invention , as defined by the appended claims .	4
fig1 shows the cross section of a typical optical mouse . shown is a light source ( led or vcsel ) 100 , from which light is directed / focused onto an object ( table , desk , paper , mouse mat ) 110 , and the resulting image observed on an optical sensor 120 which tracks movement . typically there are low - friction pads 130 mounted on the optical mouse to reduce friction and allow the mouse to move smoothly over the surface . typically there are one or more buttons on the top of the mouse ( not shown ), and usually a scroll wheel or tilt wheel 140 . fig2 shows a cross section of a mouse device according to one embodiment of the invention . this mouse includes a second optical sensor unit 250 and associated light source 260 . preferably the “ mouse surface ” 270 provided by this second sensor arrangement 250 , 260 is positioned directly underneath the position of the index finger when it is in a relaxed or comfortable state . consequently the sensor unit 250 may receive an image based on light reflected off an object , such as a finger , on the mouse surface 270 . the first optical sensor 220 and light source 200 are located on a first , main substrate ( printed circuit board , pcb ) 280 . the second optical sensor ( and associated light source ) is mounted on a second substrate ( pcb ) 290 . as an alternative to the arrangement depicted , the mouse surface could be on a side of the device ( with a plane approximately perpendicular to that depicted ) for manipulation by a thumb . fig3 shows an improved mouse from that of fig2 . by careful design of the mouse housing , the second optical sensor 250 and associated light source 260 has been mounted on the same substrate 280 as the first optical sensor 220 . this reduced the thickness and provides greater comfort to the user and also decreases the manufacturing cost . fig4 illustrates one of a number of exemplary implementing architectures according to an embodiment of the invention . it shows the first motion sensor ( looking down ) 220 , the second motion sensor ( looking up ) 250 and the controller 400 , which may be an i2c or spi or similar control interface . in particular , the connections of the “ control ,” “ motion ,” ( used to signal if the sensor has detected movement ) and ( optionally ) “ shutdown ,” ( used by a host to power down a sensor to save energy ) pins are shown for the sensors 220 , 250 and controller 400 . in this example “ motion ” and “ shutdown ” are independently connected to the controller device 400 . the output from the controller 400 is preferably a usb ( universal serial bus ) output or may even be a signal suitable for rf ( radio frequency ) modulation , in the case of a wireless mouse . the disadvantage of this system is the extra wires and input pins used add to the complexity and cost of the mouse . fig5 shows an optimized system where the controller device 400 is connected to only one sensor 250 . due to size constraints , the down - facing sensor { desk } 250 has more space available than the up - facing { finger } sensor 220 . therefore , the down - facing sensor 250 would typically receive the inputs from the up - facing sensor 220 and modify / relay these to the controller 400 . in the arrangement of fig4 , the decision to use either the down - facing sensor or up - facing sensor is made by the controller device 400 . in the arrangements of fig5 & amp ; 6 , the up facing sensor 220 would be programmed ( typically via the control interface ) with the speed threshold and the switching between the sensors being made by up facing sensor 220 . fig6 shows a more efficient system architecture which may be possible , depending on the control bus uses . for example , if an i2c bus is used , there is no need to have a control input on the down - facing sensor 220 , thus dispensing with the need of two extra pads / connections on the device . furthermore , the i2c bus supports multiple ( slave ) devices , which means that the two sensors 220 , 250 can be connected in parallel . in a main embodiment , an aspect to the invention is the operation of the device , in that the device operates by using the two control signals from the two optical sensors in a co - operative manner so as to output a single navigation output . for large movements and high speed operation , the mouse itself is moved across the surface below it , and motion data from the down - facing sensor 220 is used . for high precision movements , the mouse is kept largely stationary and the finger ( typically index ) is moved over the mouse surface 270 of the device . as the human body possesses fine motor control on the fingers , this operation results in a device which provides increased accuracy control . in order to best achieve this operation , data from the down facing sensor 220 should be ignored for the purposes of control when the mouse is largely stationary , or its speed is below a threshold level . as noted above , the output from the two sensors provides for a single navigational output . this is as opposed to an output that comprises two separate positional signals as is the case with a mouse and scroll wheel , where the mouse controls a cursor and the scroll wheel controls the scrolling in a window . in the present embodiment , the two control signals would , for example , control the same cursor , providing a coarse control and fine control of the cursor . clearly , control is not limited to that via a cursor , and the control method could be any other suitable method , including scroll , zoom etc . fig7 shows a plot of the speed of the mouse as detected by the down - facing sensor 220 against its actual speed for a mouse configured in this way . when the detected speed of the mouse is above a certain threshold t , for example , 2 - 5 mm / sec , the navigation data from the down - facing sensor 220 is used , and the reported speed increases linearly with increase in actual speed ( of course , this relationship does not need to continue in a linear fashion but instead may “ accelerate ” as is known in the art ). during this second period , data from the up facing sensor 250 is being ignored , and the sensor 250 and corresponding light source 260 may in fact be switched off . when the speed drops below the threshold t , the data from the down - facing sensor 220 is disregarded and the reported speed drops to zero ( first period on graph ). during this period data from the up - facing sensor 250 is used instead . this technique avoids small nudges in the mouse when a user is sliding a finger on the top surface from being used as valid cursor movement data . optionally , the output resolution ( counts per inch ) from the two sensors can be made different , such that the down - facing sensor outputs 800 cpi , i . e . one inch of travel outputs 800 counts , while the up facing sensor outputs 200 cpi . therefore , in the latter case , the finger has to move further to output the same number of counts . this decrease of sensitivity increases the positional accuracy of the system . the different output counts may be achieved either by changing the motion gain on the sensor or by varying the magnification in the optics (× 0 . 5 vs × 0 . 25 ) or by using sensors with different array sizes ( 20 * 20 pixels vs 40 * 40 pixels ). fig8 shows a graph similar ( axes are scaled the same ) to that of fig7 for the up facing sensor 250 during the first period of graph 7 . it can be seen that the reported speed increases linearly with actual speed of the finger on the sensor , but with a different slope than that of fig7 , representing the difference in output resolution . of course , the reported speed on this graph drops to zero should the mouse speed recorded by the down facing sensor 220 pass the threshold value t . it should be noted that the output from a mouse is rarely the actual “ speed ,” but is usually measured in counts . the speed is deduced by the controller , pc or mobile phone handset by monitoring the speed and time , i . e . speed = distance / time . speed is used on fig7 and 8 as it clearly explains the operation of the device . the above embodiments are for illustration only and other embodiments and variations are possible and envisaged without departing from the spirit and scope of the invention .	6
fig1 a is a top perspective view and fig1 b is a bottom perspective view of a trading card 10 having features of the present invention with the trading card 10 in a folded configuration 12 . as provided herein , the trading card 10 can easily be moved between the folded configuration 12 and an unfolded configuration 14 illustrated in fig2 a - 2c . the trading card 10 , for example , can be a collectible item or can be used is sports or entertainment games . in one embodiment , the trading card 10 includes a viewing lens 16 , one or more images 18 ( illustrated as an “ x ”), a front wall 20 , a back wall 22 , a bottom wall 24 , and a top wall 26 . in this embodiment , when the trading card 10 is in the unfolded configuration 14 , a user ( not shown ) can view the image 18 through the viewing lens 16 . alternatively , when the trading card 10 is in the folded configuration 12 , the user is not able to view the image 18 through the viewing lens 16 . the size and shape of the components of the trading card 10 can be varied to suit the desired design requirements of the trading card 10 . the design of the viewing lens 16 can be varied pursuant to the teachings provided herein . for example , the lens 16 can be a piece of glass , plastic , or other transparent material . in one embodiment , the lens 16 is a magnifying glass that enlarges the image 18 on the piece of film 18 . the image 18 for example , can include one or more characters , sports athletes , celebrities , an entertainers , statistics , information , instructions , a game field or arena , an image used in a game , data , a character , an autograph , an animal and / or landscape . in one embodiment , the image 18 is positioned on a piece of rectangular film 28 . the film 28 can be at least partly transparent . alternatively , the image 18 can be positioned on another medium and / or the film 28 could have another shape . additionally , in one embodiment , the film 28 is fixedly secured to the trading card 10 . alternatively , for example , the film 28 could be selectively removable from the back wall 22 . with this design , the film 28 could be interchangeable . the front wall 20 retains the viewing lens 16 . the back wall 22 retains the image 18 . the bottom wall 24 and the top wall 26 each extend between and maintain the front wall 20 and the back wall 22 spaced apart when the trading card 10 is the unfolded configuration 14 . in one embodiment , each wall 20 , 22 , 24 , 26 is generally rectangular shaped and each wall 20 , 22 , 24 , 26 includes a first connected edge 30 a , a second connected edge 30 b that is opposite the first connected edge 30 a , and a pair of opposed unconnected edges 30 c . in one embodiment , ( i ) the first connected edge 30 a of the front wall 20 is secured to the first connected edge 30 a of the top wall 26 ; ( ii ) the second connected edge 30 b of the front wall 20 is secured to the first connected edge 30 a of the bottom wall 24 ; ( iii ) the first connected edge 30 a of the back wall 22 is secured to the second connected edge 30 b of the top wall 26 ; and ( iv ) the second connected edge 30 b of the back wall 22 is secured to the second connected edge 30 b of the bottom wall 24 . in one embodiment the trading card 10 can be slightly weakened ( e . g . embossed , scored , or crimped ) at the connections between the walls 20 , 22 , 24 , 26 to facilitate relative movement of the walls 20 , 22 , 24 , 26 so that the trading card 10 can be easily moved between the configurations 12 , 14 . in one embodiment , the trading card 10 is perforated , e . g . including a line of holes , at the connections between the walls 20 , 22 , 24 , 26 to facilitate relative movement of the walls 20 , 22 , 24 , 26 . additionally , as illustrated in fig1 a and 1b , in the folded configuration 12 , ( i ) the walls 20 , 22 , 24 , 26 are all substantially parallel to each other , and ( ii ) the viewing lens 16 and the film 28 are substantially parallel to each other . further , in the folded configuration 12 , ( i ) the front wall 20 and the top wall 26 are substantially coplanar , and ( ii ) the bottom wall 24 and the back wall 22 are substantially coplanar . in one embodiment , in the folded configuration 12 , the trading card 10 is generally flat , rectangular shaped and has a length of between 2 and 6 inches , a width of between approximately 1 . 5 and 4 . 0 inches , and a thickness of between approximately 0 . 0625 and 0 . 25 inches . for example , in the folded configuration 12 , the trading card 10 can be similarly sized and shaped as a standard trading card having a length of approximately 3 . 5 inches , a width of approximately 2 . 5 inches , and a thickness of between approximately 0 . 06 and 0 . 2 inches . fig2 a is a top , front perspective view of the trading card 10 in an unfolded configuration 14 with a pair of tabs 34 ( only one is illustrated in fig2 a ) in an unlocked position 36 , fig2 b is a top , front perspective view of the trading card 10 in the unfolded configuration 14 with the tabs 34 ( only one is illustrated in fig2 a ) in a locked position 38 , and fig2 c is a bottom , rear perspective view of the trading card 10 in the unfolded configuration 14 with the tabs 34 in the locked position 38 . in the unfolded configuration 14 , the user can easily view the image 18 through the viewing lens 16 . fig2 a - 2c illustrate that in the unfolded configuration 14 , the trading card 10 ( i ) is now generally rectangular tube shaped having open sides ; ( ii ) the front wall 20 and the back wall 22 are substantially parallel and spaced apart ; ( iii ) the bottom wall 24 and the top wall 26 are substantially parallel and spaced apart ; ( iv ) the film 28 and the viewing lens 16 are substantially parallel , space apart , and are aligned so that the film 28 can be viewed through the viewing lens 16 ; ( v ) the bottom wall 24 extends between the front wall 20 and the back wall 22 ; and ( vi ) the top wall 26 extends between the front wall 20 and the back wall 22 . fig2 a also illustrates a portion of the trading card 10 in the folded configuration 12 ( illustrated in phantom ). in fig2 a , arrow 40 illustrates movement of the trading card 10 from the folded configuration 12 to the unfolded configuration 14 . more specifically , three of the walls move relative to the other wall during movement between configurations 12 , 14 . for example , during movement from the folded configuration 12 to the unfolded configuration 14 , ( i ) the front wall 20 has pivoted relative to the bottom wall 24 from being substantially parallel to the bottom wall 24 in the folded configuration 12 to being substantially perpendicular to the bottom wall 24 in the unfolded configuration 14 ( approximately 90 degrees rotation ); ( ii ) the back wall 22 has pivoted relative to the bottom wall 24 from being substantially parallel to and in substantially the same plane as the bottom wall 24 in the folded configuration 12 to being substantially perpendicular to the bottom wall 24 in the unfolded configuration 14 ( approximately 90 degrees rotation ); ( iii ) the front wall 20 has pivoted relative to the top wall 24 from being substantially parallel to and in substantially the same plane as the top wall 26 in the folded configuration 12 to being substantially perpendicular to the top wall 26 in the unfolded configuration 14 ( approximately 90 degrees rotation ); ( iv ) the back wall 22 has pivoted relative to the top wall 26 from being substantially parallel to the top wall 26 in the folded configuration 12 to being substantially perpendicular to the top wall 26 in the unfolded configuration 14 ( approximately 90 degrees rotation ); and ( v ) the top wall 26 has moved relative to the bottom wall 24 from being substantially parallel and adjacent to the bottom wall 24 in the folded configuration 12 to being substantially parallel and spaced apart from the bottom wall 24 in the unfolded configuration 14 . it should be noted that movement from the unfolded configuration 14 to the folded configuration 12 results in the opposite motion described above . as mentioned previously , the trading card 10 includes one or more tabs 34 that are moved between the unlocked position 36 ( illustrated in fig2 a ) and the locked position 38 ( illustrated in fig2 b and 2c ). arrow 42 in fig2 a and 2b illustrate movement of one tab 34 from the unlocked position 36 to the locked position 38 . with the tabs 34 in the unlocked position 36 , the trading card 10 is free to move between configurations 12 , 14 . however , when the tabs 34 are in the locked position 38 , the tabs 34 inhibit movement of the trading card 10 from the unfolded configuration 14 back to the folded configuration 12 . stated in another fashion , the tabs 34 in the locked position 38 hold and maintain the trading card in the unfolded configuration 14 . the design , number , and location of the tabs 34 can vary . in the embodiment illustrated in fig2 a - 2c , the tabs 34 are a portion of the bottom wall 24 that has been partly cut from the bottom wall 24 and rotated . in the unlocked position 36 , the tab 34 is generally parallel and coplanar with the rest of the bottom wall 24 . in this position , the trading card 10 is free to move between configurations 12 , 14 . in the locked position 38 , each tab 34 ( i ) has been rotated 90 degrees relative to the rest of the bottom wall 24 , ( ii ) is adjacent to the front wall 20 , and ( iii ) extends generally perpendicular to the front wall 20 and the rest of the bottom wall 24 . with this design , an edge of the tab 34 engages the inside of the front wall 20 to inhibit movement of the trading card 10 from the unfolded configuration 14 to the folded configuration 12 and to stabilize the trading card 10 in the unfolded configuration 14 . additionally , in certain embodiments , the notches in the bottom wall 24 and the tabs 34 provide a convenient position to hold the trading card 10 in the unfolded configuration 14 . it should be noted that the notches and tabs 34 can be wider so that larger fingers can fit in the notches and tabs 34 . it should be noted that in one embodiment , opposite walls are generally the same size and configuration . for example , the front wall 20 and the back wall 22 have substantially the same size and configuration . further , the top wall 26 and the bottom wall 24 have substantially the same size and configuration . additionally , in one embodiment , the bottom wall 24 includes an arch shaped wall opening 46 located near the back wall 22 . in certain embodiments , in the folded configuration 12 , before the trading card 10 has ever been moved to the unfolded configuration 14 , the scored or weakened areas can be relatively stiff . the wall opening 46 can provide a finger hole , e . g . a place to push , to start to move the trading card 10 from the folded configuration 12 to the unfolded configuration 14 for the first time . after the trading card 10 has been moved between the configurations 12 , 14 a number of times , the wall opening 46 may not be necessary . fig3 a is an exploded view of the beginning components , and fig3 b is an exploded perspective view of one non - exclusive , embodiment of the trading card 10 . fig3 a illustrates that in this embodiment , the trading card 10 can be made out of the viewing lens 16 , the piece of film 28 , and multiple cards 48 . in fig3 a , the trading card 10 includes a first card 48 a , a second card 48 b , and a third card 48 c . in one embodiment , each of the cards 48 a , 48 b , 48 c is generally rectangular shaped and the same size . for example , each of the cards 48 a , 48 b , 48 c can be a piece of card stock . in one embodiment , each of the cards 48 a , 48 b , 48 c is made of 24 points card stock . in fig3 a and 3b , each of the card stocks 48 a - 48 c includes a distal end 48 d and a proximal end 48 e . fig3 b illustrates that the card 48 a - 48 c have been die - cut and scored prior to assembly . more specifically , fig3 b illustrates that ( i ) a lens aperture 50 has been die cut from the first card 48 a ; ( ii ) a first cut 52 ( illustrated as dashed line ) was made in the first card 48 a across a portion of the first card 48 a to provided a weakened area for the front wall 20 to bend relative to the top wall 26 ; ( iii ) a lens aperture 54 has been die cut from the second card 48 b ; ( iv ) a rectangular shaped intermediate aperture 56 has been die cut from the second card 48 b ; ( v ) a pair of cuts 58 have been made at the proximal edge of the intermediate aperture 56 ; ( vi ) a rectangular shaped film aperture 62 has been die cut from the second card 48 b ; ( vii ) each of the tabs 34 is made with a pair of spaced apart , cuts 64 made in the third card 48 c ; ( viii ) a second cut 66 ( illustrated as dashed line ) was made in the second card 48 b across a portion of the second card 48 b to provided a weakened area for the rear wall 22 to bend relative to the bottom wall 26 ; ( ix ) the semicircular wall opening 46 has been die cut from the third card 48 c ; and ( x ) a rectangular shaped film aperture 68 has been die cut from the third card 48 c . as mentioned above the three card 48 a - 48 c are assembled together to form the trading card 10 . referring to fig3 b , ( i ) the viewing lens 16 is secured to the second card 48 b over the lens aperture 54 , ( ii ) the lens aperture 50 of the first card 48 a is positioned around the viewing lens 16 , and ( iii ) the proximal end 48 e of the first card 48 a is secured with an adhesive 70 to second card 48 b at a location that is slightly spaced apart from the proximal end 48 e of the second card 48 b . with this design , a portion of the first card 48 a and a portion of the second card 48 b cooperate to form the front wall 20 . additionally , the first card 48 a defines the top wall 26 . further , ( i ) the distal end 48 d of the first card 48 a is secured with an adhesive 72 to the distal end 48 d of the second card 48 b , ( ii ) the distal end 48 d of the third card 48 c is secured with an adhesive 74 to second card 48 b at a location that is slightly spaced apart from the distal end 48 d of the second card 48 b with the piece of film 28 positioned therebetween aligned with the film apertures 62 , 68 , and ( iii ) the second card 48 b is separated at the cuts 58 . with this design , a portion of the second card 48 b and a portion of the third card 48 b cooperate to form the rear wall 22 . further , the third card 48 c defines the bottom wall 24 . finally , the proximal end 48 e of the second card 48 b is secured with an adhesive 76 to the proximal end 48 e of the third card 48 b . it should be noted that the adhesives 70 , 72 , 74 , 76 can be replaced with another type of fastener . it is to be understood that the trading cards 10 disclosed herein is merely illustrative of the presently preferred embodiments of the invention and that no limitations are intended to the details of construction or design herein shown other than as described in the appended claims .	6
the presently disclosed subject matter provides a decision support software system that predicts potential disruptive events , contingencies , in a distribution system before they happen based on , for example , machine learning , and computes and communicates contingency and real - time management decisions to most efficiently allocate available resources ( e . g ., electricity ) to carry out pre - emptive actions ( e . g . preventative maintenance , curtailment of load , etc .) in order to prevent resource shortfalls ( e . g ., electricity outages ), additional infrastructure harm or failure , and associated harm to the public . referred to herein as the dynamic contingency avoidance and mitigation system ( dcams ), the system simultaneously estimates future needs and interactions and responds to real - time events to provide accurate , controller - based costing and pricing of the commodity ( e . g ., reliability based pricing of electric service in a micro - load pocket ), curtailment actions , and management mechanisms in order to prevent outages , equipment failure , emergencies , and contain events that have already taken place . in various embodiments of the presently disclosed subject matter , dcams communicates contingency and real - time management decisions to utilities and dr owned and operated by their customers . this optionally , combined with lean management principles , provides a dcams that both estimates future needs and interactions and responds to real - time events to provide accurate , preventive maintenance , controller - based pricing , curtailment and load pocket management mechanisms . dcams can recommend additions from dr , load shedding and other operations such as switching , crew deployment , and improved work processes to reduce the risk of power disruptions , equipment failure , and harm to people . the dcams enhances the safety and security of the distribution system ( e . g ., an electrical grid ) by improving reliability and safety on at least two fronts : the first is through the use of the simulation component to predict the effects of possible control actions , thereby permitting both human and computer decisions to be made with a better understanding of the ramifications of a particular sequence of actions ( e . g ., an electrical simulation component ). the simulation can also be used to monitor the effects of a sequence of actions in order to detect and warn of anomalous behavior . the second is through the use principles to detect those longer - term infrastructure enhancements that are most likely to have the greatest positive impact on performance and to then recommend the stronger more successful enhancements . in this regard , the methods disclosed in u . s . published application no . wo 2009 / 117742 , hereby incorporated by reference in its entirety , can be used in conjunction with the presently disclosed dcams . in the context of an electrical grid , dcams manages additions from distributed resources such as power supply storage and generation , load shedding and other operations such as switching , crew deployment , and improved work processes to alleviate risks of power disruptions and equipment failure , and to distribute power more effeciently . dcams also allows utilities to prepare in advance and to respond in real - time to detailed customer issues such as load pocket constraints ( e . g ., low voltage condition ). by implementation of reliability based pricing and curtailment strategies , made possible via dcams , the need to build additional distribution feeders in this load pocket or build additional generating resources can be reduced or rendered unnecessary . dcams receives real - time measured load and supply modulations such as from electric vehicles , building loads , and supplies like energy storage and distributed generation and predicts future response and availability of these dr . verification of the effects of curtailment orders and pricing and cost changes is a part of the controller &# 39 ; s decision - making process . dcams is also used by transmission and distribution engineering personnel to accurately evaluate capital asset upgrade options within high risk load pockets ( e . g ., from the micro level of a large customer to the area substation level ). embodiments of the presently disclosed subject matter utilize the stochastic controller technology disclosed in u . s . pat . no . 7 , 395 , 252 , granted jul . 1 , 2008 and hereby incorporated by reference in its entirety . a machine learning system can be used to train power control system operators , for example , to take suitable actions to respond quickly to fluctuations or interruptions in electricity flow anywhere in the power grid . the controller can be configured as a computer - based simulation and training tool that learns the “ best response scenarios ” to specific events on the grid , which for example , can lead to critical failure cascades across integrated generation , transmission , and distribution grids such as the eastern north american inter - connected grid , if not controlled . for example , the subject regional and distribution power grids can be modeled using commercially available power flow and short - circuit modeling tools ( such as distribution engineering works station ( dew ), sold by edd , inc . blacksburg , va ., and epri solutions , inc . palo alto , calif .). dew can , for example , model inverter and synchronous distributed generation power flow , as well as multiple - source fault analysis . dew is in use in the power industry as a real - time simulator of a utilitys &# 39 ; distribution system , for example , in conjunction with the utilitys &# 39 ; supervisory control and data acquisition ( scada ) systems and / or its energy management systems ( ems ) and their associated data historians . dew also can be used to model regional grid behavior using , for example , federal energy regulatory commission ( ferc ) data . various types of powerflow models exist that can be used for analysis in connection with peak load leveling , peak shaving , voltage correction , right sizing of equipment , and machine learning . one embodiment of the presently disclosed subject matter provides a web service for initiation of , interactive adjustments to , historian recording of , and human and machine training in the operation of the dcams . this can be achieved through access to the outputs of an integrated workflow of a plurality of analytical computer applications for characterization and analysis of operational traits , improved management of capital and human resource allocation for maintenance and operational response , and commodity or energy transaction decisions for infrastructure - based businesses such as water , electric , oil , and gas companies . the dcams is ideal in electric economies of now and in the future , such as new york which is , or can be , dominated by electric vehicles , electric trains , subways , buses and other energy sources such as alternative wind , solar and other distributed energy generation and storage resources ( dr ). the presently disclosed subject matter can improve and account for operational responses of the workforce to events in a seamless and remotely accessible package . problems caused by the disparate nature of business , regulatory , and engineering requirements and techniques are solved through software wrappers to allow specific rules and regulations written into scripts to be read into the dcams . the presently disclosed subject matter advances the current state of the art to utilize market and dispatch mechanisms to solve congestion of energy or commodity flow and human resource allocation with the least risk and cost possible . the dcams also permits the simulation and record keeping necessary to plan for and implement new operational strategies that can in turn permit the incorporation of alternative energy sources . smart feedback from the power consumers , both large and small , to the dcams allows it to anticipate demand and demand response potential , and coordinate the operations of diverse drs and other supply to produce the least pollution and lowest carbon dioxide emissions at the lowest cost while maintaining reliability expectations . such feedback can include how much dr can respond in a given time interval in terms of reduced load and over what time frame and when such capability would be available from that dr . the dcams predicts future disruptive events in the distribution system before they happen based on , for example , machine learning , and communicates contingency and real - time management decisions to utilities and dr ( distributed energy generation and storage resources ) owned and operated by their customers . see u . s . pat . no . 7 , 395 , 252 , granted jul . 1 , 2008 and hereby incorporated by reference in its entirety . in one embodiment , machine learning ranking algorithms such as , for example , support vector machines and boosting and adaboosting for ranking of susceptibility to failure of electrical components based on predicted levels of attributes versus what is observed in real time . see , generally u . s . published application no . 2009 / 0157573 and t . zhang , “ convex risk minimization , annals of statistics , 2004 , each of which is hereby incorporated by reference its entirety . through this ranking mean time between failure ( mtbf ) is approximated for failure of assets in a predicted or forecasted future state . through a topological model of the electric distribution grid , algorithms performing sequential monte carlo analysis can be used where mean time to repair ( mttr ) of various responses that are available for restoration improvement are included in the sequential or non sequential monte carlo analysis . the mttr for these actions can be learned through experience from past directed actions first as averages and then moving to the application of prediction algorithms , as disclosed , for example , in international published application no . wo 2009 / 1177421 ( hereby incorporated by reference in its entirety . in one embodiment , the dcams employs the on - policy monte carlo control method in order to improve methods to evaluate or improve on the policy that is used to make decisions on actions such as adding electric supply from distributed generation or reducing loads at specific nodes to reduce vulnerabilities or risk . one advantage of using monte carlo methods is that it provides an alternative policy evaluation process . rather than use a model to compute the value of a state , the monte carlo methods average many options for returning to the start state . the monte carlo method can be combined with dynamic programming or adp to find policies on top of monte carlo . an overview of the dcams system , according to one non - limiting , exemplary embodiment ( 300 ), is represented in fig3 . the dcams system incorporates both predictive models ( shown in fig3 in ovals ) and real - time data from the field ( shown in rectangles ). in this embodiment , the system includes a planning system and a real world system , which receives output from the planning system to assist in controlling the electrical grid in view of real - time information from the field . the planning system is described first below . as shown in fig3 , independent system operator ( iso ) market data ( 310 ) is sent to , and processed within a predicted supply model ( 320 ) that anticipates the amount of supply needed and to be made available based on historical matches to coming weather conditions , contractual agreements of supply availability ( e . g ., interconnected electric vehicles and / or distributed generation at a specific location ), and daily and seasonal usage patterns . power flow algorithms ( 330 ) in concert with forecasted ami / cis ( automated meter intelligence / customer information system ) load data ( 340 ) is sent to a predictive model to estimate predicted loads ( 350 ) at critical locations ( e . g ., load pockets ). cis and interconnection data ( 360 ) on predominately weather dependent generation ( e . g ., solar , wind ) is sent to a weather dependent generation predictive model ( 370 ) to estimate , for example , the availability of solar and / or wind power available to supplement centralized power plant supply of electricity for a specific location . output from high resolution and low resolution weather bureau predictions such as from dtn weather forecasts and deep thunder ( dtn ) ( 380 ), a service available from ibm to provide local , high - resolution weather forecasts specific to neighborhoods , is also sent as an input to the weather dependent generation predictive model and also to a weather forecast predictive model ( 390 ). output from these weather bureau forecasts is also sent to a predictive model used to predict and display known system failures ( 400 ) some of which are highly weather likely under adverse weather conditions ( e . g ., wind fallen on overhead power lines ). the predicted and known system failures model ( 400 ) also receives real - time data from gis ( geographic information systems ) ( 410 ), vegetation management history ( 420 ), feeder management system , supervisory control and data acquisition system ( scada ) outage management system ( 430 ) and data output from the contingency analysis program ( 440 ), which is disclosed in international published application no . wo 2009 / 117741 , hereby incorporated by reference in its entirety . a scorecard system ( 450 ) sends data to a financial predictive model ( 460 ). the financial predictive model quantifies the value of smart grid technologies , which in turn relies upon measuring the cost and customer convenience of the specific use of these technologies . in addition , the scorecard system tracks outages and equipment failures . exemplary scoreboard systems according to one embodiment of the presently disclosed subject matter is described in greater detail below . a work management system or scheduler ( wms ) ( 470 ) that includes , among other things , warehouse supplies , worker availability , tool availability , vehicle availability and shop management information to send data to a model used to estimate logistical capacity ( 480 ). each of the predictive models discussed above and as shown in fig3 are transmitted to the dcams , along with information about curtailment contracts ( 490 ) and managed energy storage ( 500 ). the dcams outputs sources of predicted loads ( 520 ), predicted supply ( 510 ) and predicted risks and costs ( 530 ) for better dcams decisions . in one emodiment , dcams uses such technologies as described in u . s . pat . no . 7 , 395 , 252 , which is hereby incorporated by reference in its entirety . in the embodiment represented in fig3 , the dcams also submits recommended actions to a control center operator , or alternatively , implements those actions with electronic messages via the response manager ( 630 ). examples of recommended actions during a time of tight period of tight power supply can include , for example , instructions to add battery sources or distributed generation , instructions to stop the charging of electrical vehicles or energy storage ( 500 ) and / or to withdraw current from the electrical vehicles and / or energy storage , and to cut power to other curtailable loads ( 490 ) under contract . the system configuration ( 540 ) also receives input from real - time data from managed energy sources ( 550 ), system failures ( 560 ), actual capacity ( 570 ) and actual load ( 580 ), actual weather ( 590 ), weather dependent generation ( 600 ), actual supply ( 610 ) and realized curtailment ( 620 ) to provide real time evaluation of the state of the system at specific locations for mitigation , containment , and restoration purposes . in this example , the dcams uses a monte carlo control method in order to compute methods to evaluate or improve on the policy that is used to make decisions on actions such as adding electric supply from dr sources or reducing loads at specific nodes to reduce vulnerabilities and risk . control strategies facilitate efficient distribution of electricity by applying curtailment , by moving portable sources , by prioritizing maintenance and emergency response , as well as directing surgical replacements and upgrades to the points of greatest vulnerability . the price responsiveness of curtailable customer &# 39 ; s behavior and the times needed to deploy resources , such as batteries , is also learned by the dcams . in one embodiment , the dcams employs a data historian to record the configuration of dcams by time and date , so that any previous date and time can be recalled from memory to see the data , systems configuration , recommended actions and results of those action recommended by the dcams at that past time . the presently disclosed subject matter contains decision aids that utilize the contingency calculations to provide transparency to stakeholders . the assumptions , analytic processes , input and output data used for each analysis can be readily retrieved and re - evaluated for future auditing , training , and / or effort justification . thus , access to , input and output from all workflows , present or past , and analytical tracking of decisions made in the field is provided . it is often desired in the execution of science and engineering computations to keep a notebook with a record of all experiments and the trail and errors and successes , as well as observations and analyses of events occurring during the experiment . in performing complicated tasks such as evaluation of decision processes between various resource requirements and asset allocations in complex infrastructure systems , and design basis decisions such as improving or optimizing how electrical equipment and computational software are configured , records must be kept of all decisions so that it can later be established that they were carefully made based upon the best information available at the time . the presently disclosed subject matter can use the notebook and historian technologies disclosed , for example , in u . s . pat . no . 6 , 826 , 483 , hereby incorporated by reference in its entirety . an exemplary integrated system model notebook ( 400 ) is shown in fig4 . in this embodiment , a display layer ( 410 ) is provided that includes drill down access to a network distribution layer ( 420 ), a bulk power system layer ( 430 ) and a layer detailing connection to other large sources of electricity ( e . g ., other generating systems or connection to other systems ) ( 440 ). in this embodiment , the dcams provides the ability to , for example , control asset deployment within the smart grid ( e . g ., maintenance crews in the field , or maintenance crews working in connection with capital improvement projects based on the design model ( 450 ). power routing and virtual scada ( supervisory control and data acquisition system ) functionalities are provided within the control system ( 460 ). for example , the system can use data coming in from the remote monitoring system ( rms ) to sense the electrical load on transformers in the streets and feeders at each substation . this embodiment of the present application also provides decision support ( 470 ) of , for example , electric operations , such as decisions regarding power restoration and information about customer operations and load projections in connection thereto . also provided is the ability to provide condition - based maintenance ( 480 ) based on real - time conditions and machine learning . for example , through the use of machine learning , future events can be predicted and prevented , workflow can be dispatched to replace susceptible equipment before it breaks and maintenance scheduling can be coordinated . see u . s . published application no . 2009 / 0157573 for disclosure regarding machine learning that can be used in conjunction with this embodiment . this reference is hereby incorporated by reference in its entirety . the non - limiting embodiment shown in fig4 also receives input and facilitates process control via price signals ( 490 ) regarding the commodity or resource at issue ( e . g ., the cost of electricity ). the ability to have access to , and incorporate price signals into the calculus of process control provides for energy and asset improvement , efficiency in usage and increased customer focus and satisfaction . various embodiments of the presently disclosed subject matter allows , for example , a utility to prepare in advance and to respond in real - time to detailed customer issues such as load pocket constraints at transformer high tension vaults ( htv ) for large customers such as that in fig5 or in overhead loop feeders . this level of granularity results from accurate measurement and prediction of curtailable loads such as electric vehicles , building loads , and supplies like energy storage . verification of curtailment is a part of the controller &# 39 ; s decision - making process . the same dcams can be used by distribution engineering to accurately evaluate capital asset upgrade options within high risk load pockets ( e . g ., at the micro level of a htv ) all the way through to the area substation level . fig1 - 18 provide screenshots from a display , coupled to one or more processors , that visually presents a depiction of a portion of an electrical grid according to a non - limiting embodiment of the disclosed subject matter . an area substation is depicted to provide transmission power flow contingency models that interface with scada systems . as shown in fig1 , the user has the capability of changing the configuration of the particular portion of the electrical grid that is analyzed . for example , a transformer can be added to the system model . the user can also specify the failure of a component , and the system outputs how the other components will react . as shown in fig1 , the system incorporates design basis limitations into the model . as shown in fig1 , the system can output load shifts and how much supply ( e . g ., supply from dr ) or load reduction is required in response to a failure of a user - specified component . as shown in fig1 , the system allows for the input of load forecasts . as shown in fig1 , prospective equipment violations can also be specified based on the user - specified contingency . embodiments of the presently disclosed subject matter also provides improved infrastructure response to storms . through actual vegetation management actions and locations of electric equipment , machine learning algorithms , such as but not limited to svm and / or boosting , rankings of equipment susceptibility for a given type of storm ( e . g ., high temperature storms with strong winds from the east versus cold temperature storms with high soil moisture , with winds from the north ). in one embodiment , a machine learning system employs svm or boosting to determine the ranking and subsequent mtbf of tree - lined versus non tree lined electric equipment . vegetation management history is used within the machine learning system to predict susceptibility to impending feeder outages , given a specific type and severity of approaching storm , to drive storm anticipation and response systems . the dcams system can include software modules running on a computer , one or more processors , or a network of interconnected processors and / or computers each having respective communication interfaces to receive and transmit data . alternatively , the software modules can be stored on any suitable computer - readable medium , such as a hard disk , a usb flash drive , dvd - rom , optical disk or otherwise . the processors and / or computers can communicate through tcp / ip , udp , or any other suitable protocol . conveniently , each module is software - implemented and stored in random - access memory of a suitable computer , e . g ., a work - station computer . the software can be in the form of executable object code , obtained , e . g ., by compiling from source code . source code interpretation is not precluded . source code can be in the form of sequence - controlled instructions as in fortran , pascal or “ c ”, for example . various modifications and alterations to the described embodiments will be apparent to those skilled in the art in view of the teachings herein . for example , hardware , such as firmware or vlsics ( very large scale integrated circuit , can communicate via a suitable connection , such as one or more buses , with one or more memory devices . a load pocket “ a ” in an urban area is fed by a four transformer htv “ b ” as shown in fig5 . the utility is supplying power from four medium voltage feeders from a single substation separately to each transformer . there are various dr sources and sinks owned by a large customer inside the load pocket , which can provide additional load or nega - watts in case of needed local curtailment . there is a ‘ plug and play ’ capability of the dr to communicate presence and demand of the grid , and a combination of old and new technologies for communication in the event that curtailed load can be necessary . in order for a utility to leverage the value of dr in combination with its own distribution assets , a high fidelity control system is desirable to predict future outcomes , continously evaluate the risks to reliability and efficiency , and act on those issues that could put the system in jeopardy of failure . dcams provides granular modulation of dr in addition to load curtailment verification and control . as shown in fig6 , the load pocket information is projected coming into the dcams from the load pocket a &# 39 ; s several different dr sources that are processed in addition to the htv b load and distribution grid scada coming in from the utility &# 39 ; s equipment . without an intelligent decision support system , a utility would have to ignore the dr in the load pocket a and build out more costly capital infrastructure such as an additional feeder and transformer for htv b to supply peak load contingency supplies even though these additional dr assets exist in the local area . there is a forecast for a hot summer day in a large northeastern city in the u . s . the utility plans ahead for each specific load pocket level in its region , based on predicted weather conditions , load estimates , and availability of supply . with the addition of a new generation of electric vehicles , it is desirable that the utility knows how these dr impact its system and its load pockets . at 4 pm on the day before the predicted hot day , the utility would look to one of the dcams control consoles ( fig6 ) to plan the purchase of tomorrow &# 39 ; s power . there is a potential of supply not meeting the required load in load pocket a given the future load required to be delivered to the the four transformers in htv b . in fig6 , any load below zero balance means the utility cannot meet demand if a single emergency event of say the loss of one transformer in the htv b via an open auto outage anywhere along the length of the 4 feeders from the substation to the htv b . the dcams prediction of what might happen tomorrow is based on the weather forecast and predictions of loads and supplies associated with load pocket a in view thereof . through simulation , the controller would compute recommended actions to relieve this perceived crisis period when the load pocket a is near zero balance , this time through suppression of load by increasing the local price in load pocket a and curtailing load in htv b . as shown in fig6 , the day ahead price ( 710 ) and modified day ahead price ( 720 ) are computed given the changes made by the operator , or machine , to price setpoints of electricity . load mw ( 730 ), supply mw ( 740 ), balance mw ( 750 ) are predicted for hours after 6 am ( vertical dashed line ), modified load mw ( 760 ), modified supply mw ( 770 ) and modified balance mw ( 780 ) are also computed as a result of changes made to electricity price setpoints offered to the dr at this specific location . the decision aid recommends an announcement be sent to the customer of htv b that 1 mw of curtailable load may be required in this micro load pocket the next day from 10 am to 5 pm . in response thereto , the dcams alerts customers of large energy sinks in load pocket a , such as electric billboard customers , customers in large skyscrapers or facilities for charging electric vehicles , that voltage can be temporarily reduced . the dcams recommends to the customers that load be diverted to time periods when demand is not likely to be as high . note the “ no change in scheduling of crews ,” in the recommended actions box at the bottom of fig6 , which indicates that this decision aid also recommends that no worker actions need be taken at this time based on the risk ranking of severity of an additional contingency situation actually occurring during the curtailment event . this recommendation is evaluated using data on the availability of crews as well as on the potential of remedying the grid overloads through such actions like changes in the position of electric switches within the area &# 39 ; s electric system should an additional event happen . in this example , the dcams uses a continuously updating machine learning evaluation of the multi - objective function required to maintain sufficient levels of reliability and efficiency of the smart grid . in fig6 , the dashed lines are the predicted responses of the electric grid if the recommended changes to the pricing signals are acted on by the customers for this load pocket a as predicted or contractually obligated by agreements such as curtailment . the dcams learns the extent that load in the load pocket would change due to price responsive load ( prl ) responses in the past , and / or knowledge from previous testing that a certain number of electric vehicles can decide to become suppliers and add to capacity capability within this micro load pocket . the system operator would either accept these recommendations or perform more simulations using dcams to decide what works best to meet the next day &# 39 ; s forecasts . it is now the day the hot weather arrives in load packet a , and suddenly there is a medium voltage feeder that open auto fails , causing one transformer out of the four in fig5 to go out of service in this customer htv b . the load falls below the zero balance level load pocket a and voltage is reduced . the utility must quickly act to get the system back to above zero balance to prevent loss of power to the customers or damage to the other three transformers in htv b due to overload . in real - time , the dcams instantly and automatically curtails the charging of electric vehicles in all parking lots in load pocket a ( fig7 ). it recommends the utility also raise real - time market prices in the local area of load pocket a to entice price responsive load like electric billboards on buildings and non - emergency lighting to shut off . there is a switch that ties in more supply from nearby feeders at the substation , and dcams suggests this move after automatically performing model simulations that indicate that such a load transfer would not adversely affect other parts of the electric system . the dcams also re - dispatches crews to the location of the failed feeder as a result of detection of an additional transformer overload in htv b that places the transformer at high risk of failure at the htv b . as can be seen , the dcams , through model simulation and learning of demand and supply curves in this load pocket , makes recommendations to utilize the various levers available to the utility to maintain reliability . other potential actions that dcams might recommend to operators for field crew deployment include , but are not limited to , those set forth in the table below : one of the three remaining operational transformers in htv suddenly presents an overload anomaly , as shown in fig8 . in fig8 , the vertical axis is load . the lower line ( 810 ) is predicted load on one transformer in the htv . the upper line ( 820 ) indicates that this transformer is in danger of overheating because its load ( 820 ) has jumped from 45 % to 75 % of maximum safe operation rating ( 830 ). a transformer load variance detection system alerts operators at the utility control center when more load than expected goes to the other than planned transformers during load shifting caused by feeder outages because of open main low voltage feeders . the dcams also presents the system operator with additional curtailment recommendations to shed tranche a curtailable load customers as a result of this transformer anomaly , as indicated by the recommended actions box at the bottom of fig7 . through smart management by the dcams of dr , such as curtailing charging on electric vehicles , turning off billboards and escalators , load relief via utility switching , and crew actions , a day that is disrupted by an emergency outage and overload is managed in real time , and the system is prevented from dropping below zero balance , and a blackout in load pocket a is averted . the margin between supply and load rises above zero as indicated by the dotted line in fig7 and the transformer in htv b &# 39 ; s return to normal % of safe operational rating as seen in fig8 . a prototype of the dcams is developed , complete with a weather - driven , software simulation of test cases like the above load pocket aihtv b example with the various dr like electric vehicles , solar power , price responsive load , and curtailable loads . this example shows how the dcams would meet real field example requirements of an electrical utility company . a power utility real - time integrated operations , control management , and design architechture for dcams with loads and dr is modeled in fig9 . this model , based on graph trace analysis ( gta ), can be used as both an engineering model and an operational tool . the prototype uses model - based generic algorithms for design and control of reconfigurable interdependent systems . it &# 39 ; s use eliminates the need for large matrix solvers , using instead compositions to implement polymorphism and simplify management using dependency components to structure analysis across different systems types using an implementation of hot - swappable algorithms . the iterative nature of gta provides distributed computation that allows convergence and solution of the multi - million node models conducive for an integrated systems model of large urban utilities in seconds . having this model as a base for the controller framework provides high potential for fast simulation for operator decision support that is fast enough for real - time grid control . fig1 provides a representation of the gta algorithms acting on the system model . the integrated system model allows system operations personnel to take field actions such as automatically opening or closing breakers through use of this model . this system model platform has allowed the same algorithms , such as dew , to be used simultaneously by engineers in planning and for troubleshooting , by operators in the control room , and by crews in the field . in one embodiment , the dcams grid controller of fig9 can piggyback on the real time servers of power flow and contingency analysis algorithms , such as dew &# 39 ; s gta - based power flow algorithm shown in fig1 . the dcams can be positioned in study mode servers to map out the dynamics of the electric grid for each tomorrow through use of data from existing scada and automated meter infrastructure . upon fully learning tomorrow &# 39 ; s optimal states and control policies , the dcams controller can then be used to control all facets of electric grid operations , from management of phase angle regulators , to breakers , to load shedding , to driving energy pricing based on system constraints . the contingency analysis program tool , disclosed in international published application no . wo 2009 / 117741 and hereby incorporated by reference , can be used in conjunction with the presently disclosed subject matter , and can provide system operators with decision support and assistance in identifying operational variances , measuring risks of future outages , and providing prioritized capabilities to modulate equipment , supply , crews , and current usage to prevent impending contingency emergencies from happening . fig1 provides a summary of the stochastic controller platform disclosed in u . s . pat . no . 7 , 395 , 252 , which is hereby incorporated by reference . this stochastic controller platform can be used alone , or coupled with the dew model , described above , and used as the algorithmic computational engine in accordance with the methods and systems of the presently disclosed dcams . the stochastic controller uses approximate dynamic programming ( adp ), combined with mixed - integer nonlinear programming solvers . adp is used as a decomposition strategy that breaks the problem of continuous grid management , with its long time horizon , into a series of shorter problems that the mixed - integer nonlinear programming solver can handle . the adp framework also provides a way of treating uncertainty from both operational and financial standpoints , simultaneously . to achieve this , the stochastic controller has combined real option valuation with operational policy and action determination using the same adp algorithms within the adaptive stochastic controller . the result is maximization of real option value as a control objective that are merged control objectives driven efficient and safe operations . the adp adaptive stochastic controller optimizes by solving the hamilton - jacobi - bellman equation using a unique formulation of adp interacting with the integrated system model ( ism ) via feedback loops and a critic function , similar to the way models are used in model predictive control ( mpc ). this approach is considerably different from prior work in transmission control using dynamic programming ( i . e ., approximate dynamic programming is not equivalent to dynamic programming ). fig1 shows the system architecture and the operation of an exemplary learning system 1400 , used for a critical feature of the stochastic controller , which can be set up for training operators of a distributed electrical power grid 1600 . learning system 1400 includes a reinforcement - learning controller 1002 , optional learning matrices 1004 that are used within critic function 1003 , and a model 1006 of power flow within the utility electric grid 1600 . the subject power grid can include regional power generation , transmission , and distribution grids as well as integrated transcontinental power grids ( e . g ., the eastern interconnect f the north american power grid ). the integrated system controller approach that the dcams uses employs simultaneous modeling of business processes and scheduling of three things : assets , energy ( in the form of curtailment and supply of integrated dr and distribution grid processes ), and field crew deployment . the best use of business process modeling ( bpm ) in the dispatch and monitoring of crews via the dcams is analyzed . designing and constructing a simulation environment to test and verify the dcams is thus provided . a region within an electric utility &# 39 ; s territory is isolated so that the utlity can explore how various dr sources and sinks react under abnormal circumstances such as emergency situations . responses to dr related pricing signals is also studied . the cause and effect between the distribution grid and the charging and discharging of electric vehicles and other dr tools such as storage and generation into and out of the load pocket test sites are also analyzed . the scheduling of curtailable load , coupled with feedback by way of verification mechanisms that can eventually learn how to successfully predict how to manage loads during curtailment obligations for the entirety of the utility operating region . the dcams system can be used in concert with ami and past metering of building loads and unique supplies ( e . g , solar ) to determine the confidence of loads and supplies for a large building . predicted day ahead electric load fro a skyscraper or manufacturing facility is calculated with possible variances to this load ( top three lines in fig1 ( 110 )). with the addition of predicted solar supply for the day at this building with its expected variance ( 2σ ), the load on the grid can be lowered even though predicted load variance can widen significantly ( 120 ). energy storage ( 130 ) can be manually manipulated by the building manager , or utility if under its control , to supply dr energy into the building load to further offset requirements of the grid . alternatively , the dcams can operate the bms ( building management system ). in one embodiment , dcams can operate the bms using real options valuation based on either historical or predicted outcomes of energy market pricing or additional pricing provided by the utility in this specific location for improvements in reliability and efficiency . in addition to all the above , the dcams can provide a suggestion of resources required to respond to predicted outages during severe weather events hitting overhead utility systems . as shown in fig1 , the following attributes are input into a machine learning system to predict the resources required to respond to the coming storm emergency : soil type in the immediate area of each pole , pole design , pole digging type ( rock bore versus dug soil ), wind direction , wind speed , amounts of precipitation predicted , land gradients ( e . g ., proximity to mountains or hills ), location of trees in relation to transmission and distribution lines and roads , size of trees , elevation of equipment , in view of historical data regarding past momentary outages based on observed wind and speed . deployment strategies are then sent to the storm emergency team so that they can most effectively respond to the coming damage . assuming looking at the red ( 110 ) and blue ( 120 ) dash curves at 0800 the morning before a major storm event . the capability of determining when to actually call in additional crews , when to have called in five crews for 1600 hours and to call in other utilities for a 2300 start with an understanding in advance of when they will most like be released is very valuable planning tool . most scheduling of crews must be done many hours in advance to get them available in time to respond to outages . if one waited until all the failures already took place , then outage durations would be significantly longer than if crews were prepared and prepositioned at the right time to respond to predicted levels of storm damage . just as important is when you should start releasing crews or deciding that they not respond for the next shift do to reductions in additional storm damage . through predictions of dcams of expected damage based on storm formation and severity , there are significant reductions in the cost of responding to storms . if one were to look at the actual solid blue line ( 130 ), the actual damage can be seen , which was closely predicted at 0800 . as the storm unfolds , obviously , more accuracy at the moment will allow changes to actions to further refine the response . the presently disclosed subject matter is not to be limited in scope by the specific embodiments described herein . indeed , various modifications , in addition to those described herein , will become apparent to those skilled in the art from the foregoing description and the accompanying figures . such modifications are intended to fall within the scope of the appended claims . it is further to be understood that all values are approximate , and are provided for description . patents , patent applications , publications , product descriptions , and protocols are cited throughout this application , the disclosures of each of which is incorporated herein by reference in its entirety for all purposes .	6
details of the objects and technical configuration of the present invention and operational effects according thereto will be more clearly understood by the detailed description described below based on the accompanying drawings attached in the specification of the present invention . a first keypad and a second keypad described hereinafter may be referred to as a real keypad and a virtual keypad , respectively . the second keypad is virtually created on the first keypad , and the first keypad and the second keypad are respectively configured of an independent character key structure and independent codes and provided with an independent character input mode . in addition , character input on the first keypad is accomplished by a tapping action , and character input at the second keypad is accomplished by a touch move action such as sliding ( pushing ), flicking or the like . fig1 is a block diagram schematically showing the configuration of a character input device according to an embodiment of the present invention , fig2 is an exemplary view showing the structure of a first keypad information database according to an embodiment of the present invention , fig3 is an exemplary view showing the structure of a second keypad information database according to an embodiment of the present invention , fig4 is an exemplary view showing a first keypad according to an embodiment of the present invention , fig5 is an exemplary view showing forms of second keypads visibly created on a first keypad according to an embodiment of the present invention , fig6 is an exemplary view showing forms of character keys created by a second keypad creation unit according to an embodiment of the present invention , and fig7 is an exemplary view showing forms of character keys and assignment of codes on a second keypad according to an embodiment of the present invention . referring to fig1 , a character input apparatus 100 includes a touch screen 110 , a storage unit 120 , a database 130 , a first keypad creation unit 140 , a first key touch recognition unit 150 , a second keypad creation unit 160 and a second key touch recognition unit 170 . the touch screen 110 includes a display unit 112 and a touch panel 114 . the display unit 112 displays a state of the character input apparatus 100 . at this point , the display unit 112 may be implemented in a liquid crystal display ( lcd ) or the like . the touch panel 114 is mounted on the display unit 112 and provided with a touch sense unit ( not shown ) and a signal conversion unit ( not shown ). the touch sense unit is an element for sensing whether or not a touch device touches the touch screen and senses generation of touch by detecting changes of , for example , resistance , capacitance or the like . here the touch device may include a hand of a user , a touch pen , a stylus pen , a mouse and the like . the signal conversion unit converts changes of physical quantity into a touch signal . although the touch sense unit may be configured of a touch sensor of a capacitive overlay , a resistive overlay , an infrared beam or the like or configured of a pressure sensor , it is not limited thereto and may include all kinds of sensors capable of sensing touch or pressure of an object . the touch screen 110 may also include an apparatus having an interface capable of character input only through a touch action on a specific character key , without directly touching the character key . the storage unit 120 performs a function of storing programs and data needed for operation of the character input apparatus 100 . the database 130 includes a first keypad information database 132 and a second keypad information database 134 . the first keypad information database 132 stores a coordinate value according to the form and size of each of character keys configuring the first keypad , a center point coordinate value or a center point color value of each of the character keys arranged on the first keypad , a character code and a character label corresponding to the center point coordinate value or the center point color value , and the like . here , a form of a character key configuring the first keypad may be a rectangle , a circle , a straight line , a dot , a character , a color or the like , and the form or size of a character key may be arbitrarily determined and visibly or invisibly expressed . a character key of a color form is configured in a photo , a picture or the like . the first keypad information database 132 stores information on the first keypad in the form of a character key layout table as shown in fig2 . referring to fig2 , a center point coordinate value “( 30 , 40 )” of a first key arranged on the first keypad , a center point color value ( color code ) “ red ( 02 )” of the first key , a character code “ 0041 ” of the first key , a character label “ a ” of the first key and the like are stored in the first keypad information database 132 . information on the first keypad stored in the first keypad information database 132 is provided to the first keypad creation unit 140 in the case of character input mode . the second keypad information database 134 stores a coordinate value according to the form and size of second keypad corresponding to each of the keys arranged on the first keypad , a center point coordinate value or a center point color value of each of the character keys arranged on the second keypad , a character code and character label on the second keypad corresponding to the center point coordinate value or the center point color value , a character code and a character label on the second keypad corresponding to the character code of the first key and a touch move direction and the like . here , a form of a character key configuring the second keypad may be a rectangle , a circle , a straight line , a dot , a character , a color or the like , and the form or size of a character key may be arbitrarily determined and visibly or invisibly expressed . the coordinate value of a character key arranged on the second keypad may be expressed as a single coordinate value in the case of a character key of a dot form and as a plurality of coordinate values in the case of a character key having an area formed as a straight line , a rectangle , a polygon or a circle . for example , the coordinate value may be previously determined as one or more coordinate values in the case of a character key of a dot form , coordinate values of about three points ( three pixels ) in the case of a character key of a straight line form , or less than the number of coordinate values expressing an area in the case of a character key having an area . in addition , if a representative coordinate value of a character key is selected among the plurality of coordinate values allocated to each character key as a center point coordinate value and the center point coordinate value is defined in the second keypad information database 134 in advance , the center point coordinate value of a corresponding character key is obtained when a specific character key is touched . since the second keypad information database 134 stores information on the second keypad for each of the keys arranged on the first keypad and a corresponding character code is assigned to a character key arranged on the second keypad , the second keypad can input character keys . the second keypad information database 134 stores information on the second keypad in the form of a character key layout table as shown in fig3 . fig3 a shows a case of storing a center point coordinate value of a character key arranged on the second keypad and a character code and a character label on the second keypad corresponding to the center point coordinate value . in this case , a center point coordinate value “( 40 , 50 )” of a character key arranged on the second keypad , character code “ 0042 ” of the character key , a character label “ b ” of the character key and the like are stored in the second keypad information database 134 as information on the second keypad . fig3 b shows a case of storing a center point color value of a character key arranged on the second keypad and a character code and a character label corresponding to the center point color value . in this case , a center point color value “ red ” of a character key arranged on the second keypad , a center point coordinate value “( 50 , 50 )” of the character key , a character code “ 0043 ” of the character key , a character label “ c ” of the character key and the like are stored in the second keypad information database 134 as information on the second keypad . fig3 c shows a case of storing a character code and a character label on the second keypad corresponding to a character code of a first key and a touch move direction . in this case , a code value “ 0043 ” of the first key , a touch move direction “ right ”, a character code “ 0044 ” of a character key arranged on the second keypad , a character label “ f ” of the character key and the like are stored in the second keypad information database 134 as information on the second keypad . here , a value of the character code of a character key arranged on the second keypad may vary according to combination of the code value of the first key and the touch move direction . the character key layout table of the second keypad as shown in fig3 is stored in the system as a character array and character code format file of the second keypad using a program . character keys belonging to the second keypad may be used by previously marking together with the first key on the first keypad . that is , a predetermined number of character keys around the first key may be displayed on the second keypad , or a predetermined number of character keys highly probable to be used may be displayed on the second keypad based on a character key use pattern . in the case of character input mode , the first keypad creation unit 140 displays the first keypad configured of at least one or more character keys on the touch screen 110 . at this point , the first keypad creation unit 140 creates the first keypad configured of character keys having at least one of the forms including a dot , a straight line , a curved line , a polygon , a circle and a color . the first keypad created by the first keypad creation unit 140 may be set in advance , and it may be a keypad having a general qwerty type key array as shown in fig4 a , a character keypad based on twelve keys as shown in fig4 b , or a keypad having its own structure as shown in fig4 c . that is , the first keypad or the second keypad may be configured in the form of allocating and arranging character keys of each country on a standard key array of a computer such as qwerty or may be configured in the form of allocating character keys of each country to be overlapped with a key on a keypad having a key array of a small number of keys . in addition , the first keypad or the second keypad may be a keypad configured of character keys designed in a unique structure such as a color picture or the like . in addition , the first keypad or the second keypad may be implemented in a keypad configured of a subset of character keys in the rows and columns of a keyboard having a character array the same as that of a computer keyboard , a keypad configured of some character keys of the characters on a standard 10 - key array of a telephone , or a keypad configured of character keys configured in a unique structure such as a color or figure type keypad . the first keypad creation unit 140 performs a function of providing the first keypad to the display unit 112 of the character input apparatus 100 in response to a request from a user . if touch of the first key is sensed on the first keypad , the first key touch recognition unit 150 acquires a character code corresponding to the value of the first key from the first keypad information database 132 and calls the second key touch recognition unit 160 . here , the first key is a key initially input by touch among the character keys on the first keypad , and it may perform a function of starting creation and display of the second keypad when the first key is input . the first key touch recognition unit 150 acquires the center point coordinate value or the center point color value of the initially touched first key among the character keys arranged on the first keypad . since a touch panel is basically provided with pixel data , the first touch key recognition unit 150 may acquire the center point coordinate value ( x , y ) of the key at the touch start point . in addition , if the first keypad is created on a specific picture , the first key touch recognition unit 150 may also acquire the center point color value of the key at the touch start point . if the center point coordinate value or the center point color value of the initially touched first key is acquired , the first key touch recognition unit 150 may acquire a character code corresponding to the center point coordinate value or the center point color value by searching the first keypad information database 132 . since character codes corresponding to center point coordinate values or center point color values of the character keys arranged on the first keypad are stored in the first keypad information database 132 , the first key touch recognition unit 150 may acquire a character code of the first key from the first keypad information database 132 . in response to the call of the first key touch recognition unit 150 , the second keypad creation unit 160 creates a second keypad including character keys in the neighborhood of the first key and virtually display the second keypad on the touch screen 110 . in addition , the second keypad creation unit 160 may create a second keypad including a predetermined number of character keys highly probable to be used together with the first key and virtually display the second keypad on the touch screen 110 . the second keypad creation unit 160 virtually create and display a second keypad arranging character keys which can be input , in at least one of the upward , downward , leftward , rightward and diagonal directions . at this point , the second keypad creation unit 160 may visibly or invisibly create the virtual second keypad inside or outside of the first key of the first keypad . in addition , the second keypad is created around the first key , and it is sufficient if the position of displaying the second keypad is inside the touch screen , and the second keypad does not need to be necessarily displayed around the touch point where a first key touch input is received . a case of creating and displaying a second keypad on the first keypad by the second keypad creation unit 160 will be described with reference to fig5 . first , fig5 a is a view showing a case of displaying a second keypad 520 on a first keypad 510 based on an english qwerty keyboard . referring to fig5 a , if a user inputs ‘ d ’ as a first key 512 , the second keypad creation unit 160 creates and displays the second keypad 520 on the first keypad 510 around the center point of the first key 512 as soon as the first key is input . at this point , character keys arranged up and down and left and right of ‘ d ’ are displayed on the second keypad 520 . next , fig5 b is a view showing a case of displaying a second keypad 560 on a first keypad 550 based on a character array abc of a telephone keypad . referring to fig5 b , if a user inputs ‘ a ’ as a first key 552 , the second keypad creation unit 160 creates a second keypad 560 around the center point of the first key 552 as soon as the first key is input and displays the second keypad 560 on the first keypad 550 . at this point , character keys arranged together with ‘ a ’ are displayed on the second keypad 560 . the second keypad creation unit 160 creates a layout of the second keypad in the form of various character keys . for example , the second keypad creation unit 160 may configure the second keypad by expressing a character key as a polygonal character key , a dot , a straight line , a curved line , a circle , a colored figure or the like having an area the same as or smaller than that of a key of the first keypad . at this point , the character key boundaries on the first keypad may be different from or the same as the character key boundaries on the second keypad . the character keys of the second keypad created in a variety of forms by the second keypad creation unit 160 will be described with reference to fig6 . fig6 a is a view expressing character keys of the second keypad by the unit of a dot ( corresponding to a pixel on a touch panel ) and displaying the second keypad expressed as dot form character keys around the first key on the first keypad . a coordinate value or a color value on a second keyboard (→ the second keypad ) is assigned to each of the dots displayed around the first key . fig6 b is a view expressing character keys of the second keypad as polygonal small keys around the center point of the first key and displaying the second keypad expressed as polygonal small keys around the first key on the first keypad . a coordinate value or a color value on a second keyboard (→ the second keypad ) is assigned to each of the polygonal keys displayed around the first key . fig6 c is a view expressing character keys of the second keypad as rectangular small keys and displaying the second keypad expressed as rectangular small keys around the first key on the first keypad . a coordinate value or a color value on a second keyboard (→ the second keypad ) is assigned to each of the rectangular keys displayed around the first key . fig6 d is a view expressing character keys of the second keypad as small keys of a straight line and displaying the second keypad expressed as small keys of a straight line around the first key on the first keypad . a coordinate value or a color value on a second keyboard (→ the second keypad ) is assigned to each of the straight lines displayed around the first key . as described above with reference to fig6 , a character key of the first keypad or the second keypad may be configured in the form of a rectangle , a circle , a straight line , a dot , a character , a color or the like , and a form or a size of a character key may be arbitrarily determined and visibly or invisibly expressed . in addition , a fingering distance of a key touch can be reduced as the size or the number of the character keys on the second keypad is reduced to be smaller than the size or the number of the character keys on the first keypad , and the distance between character keys can be optimized . the character key boundaries on the first keypad may be different from or the same as the character key boundaries on the second keypad . since the character keys of the second keypad have a variety of forms , the second keypad creation unit 160 implements the character keys of the second keypad by selecting a form from the character keys of various forms , and the implemented virtual second keypad is visibly or invisibly provided on the first keypad . in addition , a unique character code is assigned to each character key of the second keypad , and the character code is used by the second key touch recognition unit 170 on the second keypad . that is , if touch of a first key begins on the first keypad , character keys of the second keypad are created around the center point of the first key , and it becomes a state capable of character input . the forms of character keys and assignment of character codes on the second keypad will be described with reference to fig7 . fig7 a is a view showing character keys of the second keypad configured in a dot form around the first key a of the first keypad , and a unique character code such as b or c is assigned to each dot formed key . fig7 b is a view showing character keys of the second keypad configured in a rectangular form around the first key a of the first keypad , and a unique character code such as b or c is assigned to each of the rectangular keys . fig7 c is a view showing character keys of the second keypad configured in a polygonal form around the center point of the first key d of the first keypad , and a unique character code such as e or f is assigned to each of the polygonal keys . fig7 d is a view showing character keys of the second keypad configured in a straight line form around the center point of the first key d of the first keypad , and a unique character code such as e or f is assigned to each of the keys formed in a straight line . here , the center point of a character key arranged on the first keypad or the second keypad has a specific coordinate value within the character key assigned according to the form of the character key on the first keypad or the second keypad , and it is stored in the database 130 . the second key creation unit 160 may provide an interface capable of easily recognizing a character key which can be input on the second keypad by displaying a figure of the second keypad having a configuration the same as that of the second keypad in a character input window , as soon as creating the second keypad on the first keypad . at this point , the second keypad may be provided in a configuration independent from the first keypad , in which boundaries of the character keys on the second keypad are different from boundaries of the character keys on the first keypad , and a character code value assigned to each of the characters of the second keypad is also different from the those of the first keypad . if a touch move action is sensed on the second keypad , the second key touch recognition unit 170 acquires a character corresponding to the touch move action from the second keypad information database 134 and displays the character on the touch screen 110 . here , the touch move action includes dragging , flicking , sliding and the like and can be an action continued from a first key touch action . character input of a user on the second keypad virtually created on the first keypad is accomplished by a touch move action of the user , and if the touch action is completed without a touch move action , a character corresponding to the character code of the first key is output in the character input window of the touch screen 110 . assignment of an input character key according to a touch move action of a user on the second keypad may vary according to the method of implementing a character key configuring the second keypad . a character key configuring the second keypad can be implemented in an arbitrary form and size , such as a rectangle , a circle , a straight line , a dot , a character , a color or the like . a touch move direction of a user on the second keypad is the upward , downward , leftward , rightward or diagonal direction from inside or outside of the first key , and it can be any direction in which a character key of the second keypad is set . the second key touch recognition unit 170 displays a character on the touch screen 110 using at least one of the coordinate value , the color value and the touch move direction information according to the touch move action . hereinafter , a case of displaying a character using a coordinate value or a color value according to a touch move action and a case of displaying a character using touch move direction information will be described separately . first , a case of displaying a character using a coordinate value or a color value according to a touch move action will be described . in this case , the second key touch recognition unit 170 acquires a coordinate value or a color value according to a touch move action on the second keypad , extracts a character code corresponding to the acquired coordinate value or color value from the second keypad information database 134 , and displays a character corresponding to the extracted character code on the touch screen 110 . finally , a case of displaying a character using touch move direction information will be described . in this case , the second key touch recognition unit 170 acquires a coordinate value according to a touch move action on the second keypad , detects touch move direction information through an operation on the center point coordinate value of the first key and the coordinate value according to the touch move action , extracts a character code corresponding to a combination of the character code of the first key and the touch move direction information by searching the second keypad information database 134 , and displays a character corresponding to the extracted character code on the touch screen 110 . at this point , the second key touch recognition unit 170 detects the touch move direction information through a subtraction operation on the center point coordinate value of the first key and the coordinate value of the touch end point . for example , when the coordinate value of the touch end point is ( x2 , y2 ) and the center point coordinate value of the first key , which is the touch start point , is ( x1 , y1 ), the second key touch recognition unit 170 calculates x2 − x1 = dx , y2 − y1 = dy . the touch move direction information is created as move left if dx is a negative value as a result of the calculation , move right if dx is a positive value , move downward if dy is a negative value , and move upward if dy is a positive value . at this point , if the dx and dy values are the same , any one of them may have priority over the other . then , the second key touch recognition unit 170 may combine the touch move direction information with the character code of the first key , extract a character code on the second keypad corresponding to a set of the combined character code and touch move direction information from the second keypad information database 134 , and display a character corresponding to the extracted character code . the second key touch recognition unit 170 functions only in a corresponding input mode as far as a key touch is not released in the input mode of the second keypad . since a touch movement can be made in the upward , downward , leftward , rightward or diagonal direction from the first key of the user while the character key input mode of the second keypad is maintained , the second key touch recognition unit 170 may detect and recognize a coordinate value of a specific position having a code value when a touched position is moved . the character input apparatus 100 configured as described above may input a character in six combinations based on the center point of the first key , information on the character keys on the second keypad and a touch move action . specifically , the character input apparatus 100 may input a character using at least one of ( 1 ) a combination of the center point coordinate value of the first key and a coordinate value of a character key on the second keypad , ( 2 ) a combination of the center point coordinate value of the first key and a color value of a character key on the second keypad , ( 3 ) a combination of the center point color value of the first key and a coordinate value of a character key on the second keypad , ( 4 ) a combination of the center point color value of the first key and a color value of a character key on the second keypad , ( 5 ) a combination of the center point coordinate value of the first key and touch move direction information on the second keypad , and ( 6 ) a combination of the center point color value of the first key and touch move direction information on the second keypad . the character input apparatus 100 as described above may be applied to any user device provided with a touch screen . for example , the character input apparatus 100 may be applied to various devices such as a notebook computer , a mobile communication terminal , a smart phone , a portable media player ( pmp ), a personal digital assistant ( pda ), a tablet pc , a set - top box , a smart tv and the like . fig8 is a flowchart illustrating a method of inputting a character in a character input apparatus according to an embodiment of the present invention . referring to fig8 , if a character input mode is executed ( step s 802 ), the character input apparatus displays a first keypad configured of one or more character keys on a touch screen ( step s 804 ). if a first key touch is sensed on the first keypad ( step s 806 ), the character input apparatus acquires a character code corresponding to the center point coordinate value of the first key ( step s 808 ). that is , if touch of an initially touched first key is sensed , the character input apparatus acquires the center point coordinate value of the first key and acquires a character code corresponding to the center point coordinate value of the first key by searching a first keypad information database provided in advance . then , the character input apparatus creates a second keypad including character keys in the neighborhood of the first key and displays the second keypad on the touch screen ( step s 810 ) and determines whether or not a touch move action is sensed on the second keypad ( step s 812 ). at this point , the character input apparatus displays the second keypad on the first keypad and senses a touch move action such as dragging , flicking , sliding or the like . if a touch move action is sensed on the second keypad as a result of the determination at step s 812 , the character input apparatus acquires a center point coordinate value or a center point color value of a character key according to the touch move action ( step s 814 ) and extracts a character code corresponding to the acquired center point coordinate value or center point color value by searching a second keypad information database ( step s 816 ). then , if the touch movement is completed ( step s 818 ), the character input apparatus displays a character corresponding to the character code extracted at step s 816 on the touch screen ( step s 820 ). if a touch move action is not sensed on the second keypad as a result of the determination at step s 812 , the character input apparatus displays a character corresponding to the character code acquired at step 3808 on the touch screen ( step s 822 ). hereinafter , an embodiment of a case in which the center point coordinate value of the first key is ( 33 , 33 ) and a code value of character is previously assigned to a coordinate value ( 44 , 44 ) will be described . in this case , if the touch movement is completed at a coordinate value ( 44 , 44 ), the character input apparatus acquires a code value of character ‘ a ’ corresponding to the coordinate value ( 44 , 44 ) by searching the second keypad information database and displays a character corresponding to the code value on the touch screen . through the procedures described above , input of a character is completed by one touch input . fig9 is a flowchart illustrating a method of inputting a character in a character input apparatus according to another embodiment of the present invention . referring to fig9 , if a character input mode is executed ( step s 902 ), the character input apparatus displays a first keypad configured of one or more character keys on a touch screen ( step 3904 ). if an initial first key touch is sensed ( step s 906 ), the character input apparatus acquires a center point color value of the first key and acquires a character code corresponding to the center point color value of the first key by searching the first keypad information database provided in advance . then , the character input apparatus creates a second keypad including character keys in the neighborhood of the first key and displays the second keypad on the touch screen ( step s 910 ) and senses a touch move action on the second keypad ( step s 912 ). at this point , the character input apparatus displays the second keypad on the first keypad and senses a touch move action such as dragging , flicking , sliding or the like . if a touch move action is sensed on the second keypad as a result of the determination at step s 912 , the character input apparatus acquires a coordinate value or a color value according to the touch move action ( step s 914 ) and extracts a character code corresponding to the acquired coordinate value or color value ( step s 916 ). then , if the touch movement is completed ( step s 918 ), the character input apparatus displays a character corresponding to the character code extracted at step s 916 on the touch screen ( step s 920 ). if a touch move action is not sensed on the second keypad as a result of the determination at step s 912 , the character input apparatus displays a character corresponding to the character code acquired at step s 908 on the touch screen ( step s 922 ). as described above , the character input apparatus may input a character key on the second keypad by assigning a character code to a color after classifying and defining the character keys on the first keypad or the second keypad by color and individually expressing the characters in color . that is , if character keys of the second keypad existing at a position to which a touch movement can be applied from the center point of the first key are assigned with a distinguishable color such as red , blue , yellow , purple , greed or the like , these character keys can be distinguished by the value of a color . in addition , first keys on the first keypad may also be expressed in colors described above . accordingly , if a color of a touch start point , i . e ., the center point coordinates of the first key , and a color of the coordinates of the move end point are specified , the character input apparatus may acquire , output and display a character code value assigned to the color of a corresponding point . the character input apparatus may input or output a character using a character key expressed only in color without a special form . if a character key is implemented by assigning a color value as shown in fig9 , a keyboard of a special form which sets a character code to a specific color in a sheet of picture or an image can be designed and configured , and it can be utilized as a character input keyboard appropriate to a special purpose . for example , as a character input keyboard of a special purpose , it can be utilized as an id or pw ( password ) input keyboard used for a locking mechanism of a smart phone . fig1 is a flowchart illustrating a method of inputting a character in a character input apparatus according to still another embodiment of the present invention . referring to fig1 , if a character input mode is executed ( step s 1102 ), the character input apparatus displays a first keypad configured of one or more character keys on a touch screen ( step s 1104 ). if a first key touch is sensed on the first keypad ( step s 1106 ), the character input apparatus acquires a character code corresponding to the center point coordinate value or the center point color value of the first key ( step s 1108 ) and acquires a character code corresponding to the center point coordinate value or the center point color value of the first key by searching the first keypad information database provided in advance . then , the character input apparatus creates a second keypad including character keys in the neighborhood of the first key and displays the second keypad on the touch screen ( step s 1110 ) and senses a touch move action on the second keypad ( step s 1112 ). if a touch move action is sensed on the second keypad , the character input apparatus acquires a coordinate value of the touch move point ( step s 1114 ) and detects a touch move direction using the acquired coordinate value ( step s 1116 ). at this point , the character input apparatus calculates x2 − x1 = dx , y2 − y1 = dy using the coordinate value ( x2 , y2 ) of the touch end point and the center point coordinate value ( x1 , y1 ) of the first key , which is the touch start point . the touch move direction information is created as move left if dx is a negative value as a result of the calculation , move right if dx is a positive value , move downward if dy is a negative value , and move upward if dy is a positive value . at this point , if dx and dy values are the same , the dx value has priority . that is , the horizontal and vertical values are the same , the horizontal direction has priority . if step s 1116 is performed , the character input apparatus extracts a character code corresponding to a combination of the character code of the first key and the touch move direction information from the second keypad information database ( step s 1118 ). here , a combination value of the character code of the first key and the touch move direction information may be configured in the form of a set of ( character code of first key , touch move direction information ). for example , if the character code of the first key is ‘ a ’ and the touch move direction information is right , it can be configured in the form of a set like ( a , right ). in this case , the character code of the first key , the coordinate value or the color value of the center point of the first key , touch move direction information , a character code and a character label on the second keypad corresponding to the character code of the first key and the touch move direction information and the like are stored in the second keypad information database as shown in fig3 c . if the touch movement is completed ( step s 1120 ) after step s 1118 is performed , the character input apparatus displays a character corresponding to the character code extracted at step s 1118 on the touch screen ( step s 1122 ). if a touch move action is not sensed on the second keypad as a result of the determination at step s 1112 , the character input apparatus displays a character corresponding to the first key of the first keypad ( step s 1224 ). as described above , the character input apparatus may input a character using touch move direction information . that is , using the coordinate value and the color value of the center point of the first key on the first keypad , the character input apparatus may acquire a corresponding character code from the first keypad information database , detect a touch move direction according to an upward , downward , leftward or rightward touch move action , and then acquire a character code corresponding to a combination of the character code of the first key and the upward , downward , leftward or rightward touch move direction information from the second keypad information database and display a character corresponding to the acquired character code . fig1 is an exemplary view showing screens for illustrating a method of inputting a character using a qwerty keypad as a first keypad according to an embodiment of the present invention . referring to fig1 , if ‘ e ’ 1112 , which is the first key , is touched on the first keypad 1110 while a qwerty keypad is created as a first keypad 1110 as shown in fig1 a , the character input apparatus informs that it is the character key input mode of the second keypad and displays a second keypad 1130 including character keys in the neighborhood of the first key in a character input window area 1120 as shown in fig1 b . if the user performs a touch move action on the second keypad 1130 and releases the touch on a desired character key , the character input apparatus displays a corresponding character in the character input window area 1120 . fig1 is an exemplary view showing screens for illustrating a method of inputting a character using a 12 - key alphabet keypad as a first keypad according to an embodiment of the present invention . referring to fig1 , if the ‘ abc ’ key 1212 , which is the first key , is touched on the first keypad 1210 while a 12 - key alphabet keypad is created as a first keypad 1210 as shown in fig1 a , the character input apparatus informs that it is the character key input mode of the second keypad and displays a second keypad 1230 including character keys included in the first key 1212 in a character input window area 1220 as shown in fig1 b . if the user performs a touch more action on the second keypad 1230 and releases the touch on a desired character key , the character input apparatus displays a corresponding character in the character input window area 1220 . fig1 is an exemplary view showing screens for illustrating a method of inputting a character using a keypad arranging korean consonants and vowels as a first keypad according to an embodiment of the present invention . referring to fig1 , if the ‘ l ’ ( , , ) key 1312 is touched as a first key on the first keypad 1310 as shown in fig1 a , the character input apparatus informs that it is the character key input mode of the second keypad and displays a second keypad 1330 including character keys included in the first key 1312 in a character input window area 1320 as shown in fig1 b . if the user moves the touch in the direction to the point of key ‘ ’, the character input apparatus acquires a coordinate value of key ‘ ’, acquires a character code corresponding to the acquired coordinate value and displays the character ‘ ’ corresponding to the acquired character code in the character input window area 1320 if the user releases the touch at the same point . fig1 is an exemplary view showing screens for illustrating a method of inputting a character using a picture as a first keypad according to an embodiment of the present invention . referring to fig1 , if a sunflower picture as shown in fig1 a is used as a first keypad 1410 , character keys are assigned on the first keypad 1410 according to colors or positions . if the user touches area ‘ a ’ 1412 on the first keypad 1410 , the character input apparatus informs that it is the character key input mode of the second keypad and displays a second keypad 1430 including character keys assigned to the area ‘ a ’ 1412 in a character input window area 1420 as shown in fig1 b . then , if the user performs a touch move action on the second keypad 1430 and releases the touch on a desired character key , the character input apparatus displays a corresponding character in the character input window area 1420 . this corresponds to a case in which the second keypad 1430 and the character keys are invisibly created on the first keypad 1410 . according to the present invention , characters can be input rapidly and conveniently and , furthermore , error input can be reduced by doubly providing keypads in a touch or non - touch action type character input apparatus of various materials and forms . in addition , a character can be input more correctly and flexibly by virtually providing a second keypad , on which characters that can be input by touch movement of a user are displayed , when a touch start of a first key is sensed on a first keypad which is provided basically . in addition , since nine or more characters can be input through a first key touched on the first keypad when the keys of the second keypad virtually displayed on the first keypad are arranged in upward , downward , leftward , rightward and diagonal directions , a user can input a character more conveniently and correctly . in addition , a new user experience can be provided by providing a character input apparatus of various forms invisible to other people , such as an idle screen of a smart phone , a background picture of an application or web , a figure and the like . in addition , efficiency of character input can be improved by reducing a fingering distance required for character input in the character input environments of various users , improving correctness of character key touch and minimizing movements of a hand . in addition , a plurality of characters can be input through a touch start character key without pressing keys several times in inputting characters using a touch screen . in addition , speed of character input can be improved by displaying a complete character on a screen through one touch and touch move action on a touch - type keypad . while the present invention has been described with reference to the particular illustrative embodiments , it is not to be restricted by the embodiments but only by the appended claims . it is to be appreciated that those skilled in the art can change or modify the embodiments without departing from the scope and spirit of the present invention . embodiments of the subject matter and the functional operations described in this specification can be implemented in digital electronic circuitry , or in computer software , firmware , or hardware including the structures disclosed in this specification and their structural equivalents , or in combinations of one or more of them . embodiments of the subject matter described in this specification can be implemented as one or more computer program products , i . e ., one or more modules of computer program instructions encoded on a tangible program carrier for execution by or to control the operation of a data processing apparatus . the tangible program carrier can be a computer readable medium , which can be a machine - readable storage device , a machine - readable storage substrate , a memory device , a composition of matter effecting a machine - readable propagated signal , or any combination thereof . the term “ data processing apparatus ” encompasses all apparatus , devices , and machines for processing data , including by way of example a programmable processor , a computer , or multiple processors or computers . the apparatus can include , in addition to hardware , code that creates an execution environment for the computer program in question , e . g ., code that constitutes processor firmware , a protocol stack , a database management system , an operating system , or any combination thereof . while this specification contains many specifics , these should not be construed as limitations on the scope of an invention that is claimed or of what may be claimed , but rather as descriptions of features specific to particular embodiments . certain features that are described in this specification in the context of separate embodiments can also be implemented in combination in a single embodiment . conversely , various features that are described in the context of a single embodiment can also be implemented in multiple embodiments separately or in any suitable sub - combination . moreover , although features may be described above as acting in certain combinations and even initially claimed as such , one or more features from a claimed combination can in some cases be excised from the combination , and the claimed combination may be directed to a sub - combination or a variation of a sub - combination . similarly , while operations are depicted in the drawings in a particular order , this should not be understood as requiring that such operations be performed in the particular order shown or in sequential order , or that all illustrated operations be performed , to achieve desirable results . in certain circumstances , multi - tasking and parallel processing can be advantageous . moreover , the separation of various system components in the embodiments described above should not be understood as requiring such separation in all embodiments and it should be understood that the described program components and systems can generally be integrated together in a single software product or packaged into multiple software products . as described above , this specification is not intended to limit the present invention to the presented specific terms . while the present invention has been described in detail with reference to the particular illustrative embodiments , those skilled in the art can alter , change or modify the embodiments without departing from the scope and spirit of the present invention . the scope of the present invention is defined by the accompanying claims , rather than the above detailed description , and the meaning and scope of the claims and all changes and modifications derived from equivalents thereof should be interpreted as being included in the scope of the present invention .	6
the matrix 1 depicted in fig1 within its central area , is provided with a positioning portion 2 which , on both sides , is followed by two terminal areas 3 which , with respect to the positioning part 2 , are stepped in such a way that the positioning part 2 projects with a section from the plane formed by the upper edges of the two terminal areas 3 . the matrix 1 is provided with two stamped - out windows 5 ; it is preferably constructed in two layers , in which case the one supporting layer comprises a thin steel band of e . g . 0 . 05 mm thickness , upon which an equally thin , transparent strip of plastic , by way of preference of cellulose acetate , is attached . the two layers may be bonded to each other , be thermally sealed by warmth or heat or be joined together in some other way ; when in use , they form a unit , in which case the plastic strip rests against the dental filling and the steel band is at a distance from said filling , as is illustrated e . g . in fig5 . the fig2 and 3 show , in a top view and in a side view , a dental group 7 comprising three teeth , of which the center tooth has a cavity 8 which has to be filled with a plastic while the original shape of the tooth is adhered to . within the area of the dental neck 9 , as is apparent from fig3 the circumference of the tooth decreases . it is for this reason that the matrix , when engaging around the tooth to be treated and when the matrix is contracted at its two ends 3 , has to produce a conical shape in order to encircle the dental configuration tightly which , at the point of contact , is broader . that is why the wall edge towards the cervical area is shorten than the edge which faces the marginal strip of the filling , as is disclosed by fig3 . the matrix 1 reproduces the anatomical configuration of the tooth within the cervical area , i . e . within the area of the dental neck , as accurately as possible . it thereby prevents the excessive filling with filling material within this area and thus protects the marginal parodontium . in order to resist the lateral forces occurring during the insertion of the filling material , the matrix 1 is equipped with the steel band . the fig4 to 6 depict analogous representations as do the fig1 to 3 , but of closely set teeth and with a small diameter of the dental neck of the tooth to be tretaed . in this embodiment , the matrix band should likewise project cervically only a little above the approximal box in order to be wedged there . this wedging is shown particularly in fig7 on an enlarged scale . the fig4 shows a matrix 12 having a curvature 13 which is greater than that of the matrix 1 according to fig1 as well as with two windows 5 , 5 &# 39 ; and a pronounced conical stepping 15 which corresponds to the smaller circumference of the dental neck . this matrix 12 is intended to be used on a dental group 18 in which the center tooth has a cavity and a , in diameter , relatively small dental neck 20 . the matrix according to fig4 allows for this configuration by the relatively large conical stepping 15 . in fig7 two teeth are illustrated in a side view , viz . a sound tooth 25 and a tooth 26 with a cavity provided with a plastic filling 27 which is indicated in a dash - dotted manner . a matrix 28 of the type described has an externally located steel band 30 with one or several windows 31 and a plastic band 32 resting against the tooth to be treated 26 . an illuminating wedge 34 is inserted between the dental necks of the teeth 25 and 26 . the fig8 shows the top view of the teeth according to the arrangement according to fig7 in which case the two matrix ends 35 of the matrix laid around the tooth to be treated 26 are tightened with the aid of a matrix tightener 36 around the tooth by the matrix ends being seized and whereby the filling is imparted the shape desired in the fig7 and 8 . the lighting of the illuminating wedge 34 by means of an external light source permits , in this position of the parts , to cure the critical area where plastic and dental material meet as the first within the primary curing area 37 and to thereby prevent the feared shrinkage interstices between the plastic and the dental material . the areas of the plastic material which are located at the top are cured subsequently in such a way that the shrinkage of the curing manifests itself only on the free areas of the plastic and , basically , the entire plastic material can be cured so as to be devoid of the formation of any cracks or interstices . the matrix has , dependent upon the application indication , one ( for single approximal fillings ) or two windows ( for double approximal fillings ) of cellulose acetate within the approximal area . the windows make a perfect light curing within the approximal area possible . the action of the light is not restricted . the matric band is retained in position with the aid of matrix tighteners , such as the toffel wire system , the uhm system or the nystrom i and ii system . the fig9 a to 9e and 10 , 10a to 10e show premolar matrix bands , while the fig1 , 12a to 12k show molar matrix bands . the bulges 40 are clearly perceptible . the fig1 and 14 show the basic form of double - bulge matrix bands , while fig1 discloses a single - bulge embodiment . in this case the window sizes of molar bands are approximately 5 × 10 mm and the premolar bands possess a window size of approximately 4 × 8 mm . the fig1 shows a cellulose acetate strip 42 , such as is applied prior to the stamping out of the matrix with the steel band and subsequent to the windows being stamped out . fig1 shows a tooth 45 in perspective representation provided with a filling 46 which is schematically boldly framed and identified with zones 48 , 49 and 50 . an illuminating wedge 52 is acted upon by a light source with light beams 55 which , owing to the construction of the wedge , are deflected and thus cure the lowermost zone 48 when light is incident . subsequently the two zones 49 and 50 , as is apparent in a diagrammatically shown manner , are finally cured , in which case the matrices shown in the various figures appropriately encircle the plastic filling 46 so that the same can be subjected to the curing process in a geometrically correct manner . in fig1 , a device 60 for the fabrication of matrix bands is diagrammatically illustrated which comprises a plastic band roll 61 and a metal band roll 161 . the metal band of the steel band roll 161 is passed through a stamping means , by means 64 of which the pertinent number of windows is stamped out . the plastic band is removed from the roll and the stamped - out metal bands are laminated to each other in the joining station 65 by heat , adhesive or suchlike so that they are able to form an inseparable unit . the two combined bands are conveyed into a matrix punch 67 , with the aid of which the matrices 68 are fabricated and ejected possesing a form in which they are ready for use . the metal band imparts the requisite rigidity to the window matrices , which again is of advantage when the band is laid as well as in the shaping the filling . according to one of the embodiments , the matrix 1 is comprised of a thin band - shaped blank of steel or some other suitable material , it being also possible to employ plastics which do not react with the dental filling . in this band - like metallic blank , one or several window - like perforations 5 are formed which , by means of a strip - shaped blank , are covered by means of a transparent , more particularly , crystal - clear plastic , said plastic strip possessing a design which corresponds to the shape and dimensions of the steel band of the matrix 1 so that the plastic strip coincides fully with the steel band . however , the possibility also exists of disposing blanks of transparent plastic solely within the area of the window 5 in the steel band , in which case these plastic bands are dimensioned in such a way that the windows 5 are covered and that they rest with a section against the wall area of the steel band so as to make it possible to attach the plastic blanks to the steel band . as covering for the windows 5 , transparent plastic are employed , such as e . g . plastics having a cellulose base , such as cellulose acetate , or vinyl polymerisates , ps , pmma and pc . according to a further embodiment , the matrix provided with at least one window 5 is comprised of a blank constructed according to the configuration of the matrix fabricated from a transparent , crystal - clear plastic , e . g . possessing a cellulose base , such as cellulose acetate , or a vinyl polymerisate , ps , pmma and pc , in which case especially such plastics are employed as are used for optical purposes , in which a certain elasticity has to be present so as to enable one to lay the matrix around a tooth . for the formation of windows 5 , the matrix of the plastic strip is provided with a metallic coating which may e . g . be vapor - deposited while window - like areas are formed . metallized plastics of this type are produced by non - galvanic or by galvanic processes . consequently , the fabrication may be effected in accordance with the metallization process , in which low - melting metals are applied to the plastic in the form of a mist or according to the metal reduction method , in which metal salt solutions , e . g . gold , silver or copper salt solutions are reduced with the aid of formaldehyde . the materials then precipitate onto the plastic . a metal coating is also possible to effect in accordance with the vacuum deposition method . in the present case , as plastics are employed those which neither combine with the dental fillings nor are partially or completely dissolved by the latter . the advantage of using metal coated matrices resides in the simplified fabrication . large - surface blanks of a suitable plastic are coated with the aid of metals while , at the same time , a number of uncoated surface sections are formed whose number corresponds to that of the matrices then to be stamped out from the blank , which subsequently form the windows 5 . following the coating , the matrices are then stamped out of the metal - coated blank , in which case each matrix is provided with a window - like area that - is transparent . if it is intended that every matrix is to possess several windows 5 , in that case the coating process , per matrix to be stamped out , a corresponding number of transparent areas are left blank . the fig1 shows a matrix 1 of a carrier or supporting material 80 of a transparent plastic which is provided with a metallic coating 81 in which one window 5 has been left blank . it is furthermore possible for the matrix 1 to be comprised of a glass metal which is inserted in the form of a thin band or film or sheet , from which the matrix 1 is fabricated while windows 5 are produced . the number of the windows 5 constructed in the matrix 1 may be arbitrarily selected , in which case , apart from one window , the matrix 1 may be provided with two or even more than two windows disposed in side - by - side - arrangement . especially advantageous in this connection is also a latticed construction of the metallic part of the matrix so that a plurality of windows 5 is formed which are disposed in a side - by - side arrangement or on top of each other . the inherent stability of the matrix 1 is improved by means of this design while an adequate flexibility is maintained at the same time . the windows 5 possess a square , rectangular , circular or some other geometric configuration .	0
with reference initially to fig1 a triple ripple airlock is illustrated , the triple ripple airlock being indicated generally at 10 . this airlock consists of a molded clear plastic member indicated generally at 12 , the plastic member including an “ s ” shaped passageway which will be described later . extending downwardly from the “ s ” shaped passageway is a mounting stem 14 which is inserted into the rubber bung or cork 16 of a fermenting vessel 18 so as to be an airtight fit . the airlock is provided with a dust cap 20 at its upper end . the “ s ” shaped passageway includes an upwardly extending portion 22 which is in direct communication with the stem 14 , the portion 22 being essentially cylindrical in cross section . a “ u ” shaped member 24 having a circular cross section connects the portion 22 with a downwardly extending portion 26 having upper , intermediate , and lower bulbs 26 . 1 , 26 . 2 , and 26 . 3 , respectively . a further “ u ” shaped member 28 having a circular cross section connects the lower end of the downwardly extending portion 26 with an upwardly extending portion 30 provided with upper , intermediate and lower bulbs 30 . 1 , 30 . 2 , and 30 . 3 , respectively . an upwardly extending member 32 is provided with a bulb 34 at its top end , which bulb receives the dust cap 20 . a clear plastic web or flashing 36 extends between the downwardly extending portion 26 and the upwardly extending portion 30 , and also between the downwardly extending portion 26 and the upwardly extending portion 22 to keep the various parts in fixed relationship to each other . after the liquid to be fermented is placed in the vessel , which liquid may be a wine must , the vessel is sealed with an airlock at the commencement of anaerobic fermentation . to this end , a sterilizing liquid is placed in the “ s ” shaped airlock , the sterilizing liquid filling the “ u ” shaped member 28 and ½ of each of the lower bulbs 26 . 3 and 30 . 3 , the sterilizing liquid being indicated generally at sl in fig2 . the sterilizing liquid typically contains either sodium or potassium metabisulfite , although other sterilizing agents may be used . during anaerobic fermentation the yeast is less active than during the initial aerobic fermentation , and the co 2 produced with escape through the sterilizing liquid one bubble at a time . with reference to fig2 it can be seen that the “ s ” type airlock of the present invention is provided with two electrodes 40 , 42 . electrode 40 is embedded in the flashing 36 which extends between the downwardly extending portion 26 and the upwardly extending portion 30 . additional flashing 44 is provided to one side of the upwardly extending portion 30 for the receipt of electrode 42 . as can be seen from fig2 the electrodes have lower terminal ends that extend into the passageway 28 . normally the ends of the electrodes are covered with the sterilizing liquid , which conducts electricity . thus , when a voltage is applied between them , current flows between the electrodes . however , when a bubble passes through the tube 28 , the current flow between the electrodes is interrupted . dust cap 20 , shown in fig3 prevents dust from settling into the airlock when it is engaged with the top of airlock 12 . conducting members 21 connect to electrodes 40 and 42 . as illustrated in fig4 electrodes 40 and 42 are connected to control means 60 through conducting members 21 . control means 60 comprises control buttons 65 a , 65 b , 65 c , 65 d , and 65 e , and a display 70 . bottle 18 contains wine must w . control means 60 counts the number of times the current between electrodes 40 and 42 is interrupted . control means 60 determines the status of the fermenting liquid based on the history of bubbles detected . control means 60 displays the status of the fermenting liquid on display 70 . the interruption of the current between the electrodes is illustrated in fig5 . bubble 50 , created by the production of co 2 during fermentation , envelops the exposed conductive material of both electrodes . thus , with a low voltage drop across the electrodes , the gas does not conduct electricity between the electrodes . a preferred voltage drop across the electrodes is approximately 5 v , although other voltage drops might be suitable . the control means of the apparatus records each interruption in the current as a bubble event . [ 0029 ] fig6 is a schematic of an embodiment of the electrical circuit of the control means . the circuit shown comprises electrodes 40 and 42 , a 5 v source , resistor 85 , operational amplifier ( op amp ) 87 , positive and negative power supplies v + and v − to power the op amp , and processor 90 . processor 90 is a conventional microprocessor , well known to those in the electronics art . the 5 v source is connected across electrodes 40 and 42 through resistor 85 . when current exists between the electrodes , v in − is 0 v . ( the 5 v source is shorted to ground .) however , when a bubble interrupts the current through the electrodes , v in − is no longer zero . ( ground is separated from v in − by an open circuit .) v in + is connected to ground . thus processor 90 can determine the presence of a bubble between electrodes 40 and 42 from the output of operational amplifier 87 . [ 0030 ] fig7 shows a second possible embodiment of control means 60 . this embodiment comprises a plurality of control buttons 65 a , 65 b , 65 c , 65 d , 65 e , and 65 f , electrodes 40 and 42 , a 5 v source , resistor 89 , pin 88 of processor 90 , audio alarm 92 , and visual alarm 94 . pin 88 of processor 90 is connected to electrode 40 and to a 5 v source through resistor 89 . electrode 42 is connected to ground . when current exists between the electrodes , pin 88 is shorted to ground . when the current is interrupted by a bubble , pin 88 will be lifted to a non - zero voltage . ( the voltage level will depend on the resistance value of resistor 89 ). in this manner , processor 90 can determine the presence of bubbles between electrodes 40 and 42 . to use the above - described device , a measure volume of a liquid subject to fermentation , such as a wine - must , is placed in a container . ( this is typically done after a period of aerobic fermentation and a hydrometer measurement to determine the proportion of sugar remaining .) the airlock of the present invention is inserted in the neck of the container . the user programs the volume of liquid present in the container using the control buttons . in a preferred embodiment , control means 60 are configured as follows . first , the batch size must be set . button 65 a increases the batch size by 10 liters each time it is pushed . button 65 b increases the batch size one liter each time it is pushed . button 65 c accepts the batch size when it is pushed , if the batch size is non - zero . ( buttons 65 d and 65 e have no function in setup mode ). after the batch size is set , the user can enter a user specified time alarm , to be activated when the enter amount of time passes without a bubble being detected . button 65 a increases this alarm time by one hour each time it is pushed . button 65 b increases this alarm time by one minute each time it is pushed . button 65 c accepts the current alarm time . ( zero may be entered if no user specified time alarm is desired .) when the user specified alarm is set , the user can then enter an alcohol alarm level . button 65 a increases the alcohol level alarm by one percent each time it is pushed . button 65 b increases the alcohol level alarm by one tenth of one percent each time it is pushed . button 65 c accepts the current alcohol level . after the alcohol level alarm is set , the user can activate the 24 hour alarm . button 65 a enables the 24 hour alarm . button b disables the 24 hour alarm . button 65 c accepts the current 24 hour alarm status . the control means then detects the bubbles of gas escaping from the airlock and displays the status of the liquid on display 70 . the status is determined based on the history of bubbles detected by control means 60 . in one embodiment , airlock 12 is configured such that the escaping bubbles have a volume at room temperature and 1 atmosphere of pressure of 1 . 7 ml . ( it is assumed that the fermentation is done at a constant temperature , thus an equal amount of gas is contained in each bubble ). thus , by counting the number of bubbles , control means 60 can determine the amount of gas to escape from the airlock . according to calculations known in the art , the amount of alcohol generated during anaerobic fermentation can be determined based on the volume of co 2 generated ( assuming substantially all of the escaping gas is co 2 generated by fermentation ) and the amount of liquid present in the container ( input using the control buttons , as discussed above ). accordingly , control means 60 can calculate the volume of alcohol generated and display this amount on display 70 . in a preferred embodiment the buttons of the control means function as follows . button 65 a scrolls the display of the bubble events towards the most current event . button 65 b scrolls the display of the bubble events towards the least recent event . button 65 c deletes the display of the displayed event if pressed alone . button 65 d caused the control means to reenter setup mode . button 65 e silences current alarms and calls up a screen to review past alarms . display 70 is set to the most recent event when button 65 e is released . when buttons 65 c and 65 e are pressed simultaneously , past alarms are cleared . as discussed above , a user can preprogram a percentage of alcohol desired with the control buttons . in this case , control means 60 displays a countdown of the amount of alcohol still to be generated . control means 60 can include an audible alarm 94 and / or visual alarm 96 to signal a user when the desired amount of alcohol has been produced . this can be especially useful in making beverages wherein some fermentation is desired after the liquid is bottled . the alarm can be set to alert the user when a portion of the desired alcohol has been produced . the user can then transfer the beverage to individual bottles for the remaining fermentation . this is also useful for the production of a sweet beverage . the user can stop fermentation before all the sugar has been consumed by the yeast . control means 60 also includes timing means to determine the amount of time between each bubble . counting means displays the amount of time since the last bubble on display 70 . audible and / or visible alarms can be activated to alert the user after a specified time without a bubble has been reached . in one embodiment , this time period is 24 hours . in another embodiment , this time period is set by the user using the control buttons ( the user specified alarm discussed above ). a potential problem with fermentations that can take a long period of time is the evaporation of the sterilizing liquid . if the sterilizing liquid evaporated to the point wherein outside air may pass into vessel 18 , then the fermentation may be spoiled . the present invention warns a user when the level of the sterilizing liquid is low . electrodes 40 and 42 are placed in member 28 such that they are exposed to air before the liquid level drops to an extent that air could reenter vessel 18 , as shown in fig2 . control means 60 times the length of the bubbles . if the sterilizing liquid has partially evaporated , then the electrodes will be exposed to air continuously . thus , when control means 60 detects an interruption of the current that lasts an extended period of time ( in one embodiment 1 hour ), it displays a low liquid level warning on display 60 . audible and / or visible alarms may also be activated . in addition , bubble detection indicator 92 is lit when a bubble is being detected ( when current is not flowing between electrodes 40 and 42 .) this can also allow a user to determine there is a problem if the bubble detection indicator remains lit for an extended period of time . the low liquid level warning and bubble detection indicator allow a user to replace the lost sterilizing liquid before the fermenting liquid is spoiled . [ 0038 ] fig2 , and 5 show the present invention being practiced with an “ s ” type airlock . however , it should be readily apparent to one skilled in the art that other airlocks or valves may be modified to practice the present invention . fig8 - 10 illustrate several valves known in the art . fig8 shows a flapper check valve 110 . electrodes 140 and 142 contact conducting strip 145 on flapper 115 when the valve is closed . thus , when the valve is closed , current flows from electrode 140 to electrode 142 through strip 145 . when flapper 115 is forced open by gas pressure , the current flowing between electrode 140 and electrode 142 is interrupted . thus , the number of times gas escapes from the valve can be counted . the amount of gas that escapes each time is measured and programmed into control means 60 . in this manner , a fermentation process can be monitored as described above . in a similar manner , fig9 shows a piston check valve 210 comprising electrodes 240 and 242 , and valve member 215 having conducting strip 245 on a surface thereon . when the valve is closed , current flows from electrode 240 to electrode 242 through strip 245 . when member 215 is forced open by gas pressure , the current flowing between electrode 240 and electrode 242 is interrupted . fig1 shows ball check valve 310 comprising electrodes 340 and 342 and conducting ball 345 . when the valve is closed , current flows from electrode 340 to electrode 342 through conducting ball 345 . when ball 345 is forced up by gas pressure , the current flowing between electrode 340 and electrode 342 is interrupted . the amount of gas released each time the valve opens is used to determine how much gas is produced during fermentation , in the manner described above . these modifications , including the use of the practicing of the present invention with other valves not shown , is intended to be within the spirit and scope of the invention as claimed . in the present specification and claims , the word “ airlock ” is intended to mean any airlock or valve known in the art or hereafter developed that can be modified as described herein to practice the present invention . while a preferred form of this invention has been described above and shown in the accompanying drawings , it should be understood that applicant does not intend to be limited to the particular details described above and illustrated in the accompanying drawings , but intends to be limited only to the scope of the invention as defined by the following claims . in this regard , the term “ means for ” as used in the claims is intended to include not only the designs illustrated in the drawings of this application and the equivalent designs discussed in the text , but it is also intended to cover other equivalents now known to those skilled in the art , or those equivalents which may become known to those skilled in the art in the future .	6
referring now to the figures , wherein like reference numerals refer to like elements throughout the figures , there is shown in fig1 a telescoping anti - rotation attachment system 10 constructed in accordance with the principles of the present invention . the system 10 comprises a backup frame 12 , a pair of external anti - rotation support tubes 14 , and an internal telescoping support tube 16 . anti - rotation support pads 18 are disposed on the distal end of each of the external anti - rotation support tubes 14 , and an adjustable eye assembly 20 is disposed on the distal end of the internal telescoping support tube 16 . the trailer attachment system 10 , in a preferred embodiment , is made of a - 36 steel and weights approximately 660 lbs . the overall dimensions are approximately 25 in .× 54 3 / 16 in .× 74 in . during normal operation , the system 10 attaches to a pintle hook on a truck , using the eye assembly 20 , which in one embodiment comprises a 3 in . lunette eye . this eye is a standard component for trailers where the truck pintle hook is connected for attenuator transport . this eyelet should be a 20 , 000 lb . minimum standard trailer eyelet . again , referring to a preferred embodiment , the telescoping tube 16 is preferably ½ in .× 5 in .× 5 in . for an internal fixed tube 16 a and ½ in .× 6 in .× 6 in . for an external telescoping tube 16 b . the external support tubes 18 are also preferably ½ in .× 6 in .× 6 in . the anti - rotation support pads 18 preferably comprise a - 36 steel plate , preferably ½ in . thick . in the embodiment illustrated in fig1 , the pad size is approximately 6 in .× 6 in ., but it is preferably preferred that the pads 18 be larger , as shown , for example in fig1 and 12 . the two external support tubes 14 are substantially shorter than the internal telescoping tube 16 , as shown in fig1 , so that the vehicle , when traveling , can freely negotiate a complete 90 degree turn if necessary . of course , while presently preferred materials and dimensions have been disclosed herein , for the purpose of thoroughness and to ensure an enabling disclosure , those of ordinary skill in the art will recognize that alternative materials and dimensions may be selected , depending upon desired application and performance criteria , without departing from the basic principles of the invention . with respect now to fig1 - 7 , more details of the system 10 and its engagement with a truck or other suitable vehicle will become apparent . as shown in fig4 , on the rear end of the internal telescoping tube 16 is installed a stop plate 22 , which closes the end of the tube 16 . this plate acts as a stop when the trailer attenuator is being towed . when the tow vehicle is pulling the trailer attenuator , the plate 22 is larger than the outside dimension of the external telescoping tube 16 b . the stop plate 22 and the pintle hook of the tow vehicle share the load during transport of the trailer attenuator . as shown in fig4 - 7 , a cross - bar 24 is disposed across the system 10 , extending through the internal tube 16 and connecting the two external tubes 14 . a spring - loaded friction brake or lock 26 is disposed on the internal tube 16 , wherein the cross - bar intersects the internal tube 16 . a shear pin 28 is disposed in the internal fixed tube 16 a and the external telescoping tube 16 b of the internal tube 16 , and is arranged to slide down vertically between both tubes . during normal operational use , with the system 10 connected to a truck frame 30 , by attachment of the eye hook 20 to a pintle hook 32 on the truck frame 30 , the shear pin 28 is not under load . loads during operation are distributed between the pintle hook and a stop plate 34 on the truck . this condition , prior to impact , is illustrated particularly in fig2 . however , during an impact , the shear pin 28 undergoes double shear . once the pin has sheared , as shown in fig3 , the system 10 slides forwardly against the plate 34 on the truck . the anti - rotation arms 14 slide forwardly , and the anti - rotation support pads 18 on those arms 14 bump up against the truck plate 34 , thus preventing the attenuator from rotation around the end of the truck . at the point at which the system 10 bumps up against the truck plate , the system is converted from a uni - attachment to a tri - support system , with two outward support arms 14 preventing angular rotation and the central pintle hook attachment providing direct central support . to reduce rotation of the attenuator in angled impact situations , the telescoping anti - rotation attachment system 10 has an anti - rotation locking mechanism . the anti - rotation locking mechanism is a one - direction friction lock 26 incorporated into the internal and external telescoping tubes 16 a and 16 b , respectively . in an impact of sufficient force to shear the shear pin 28 , the inner support tube 16 is released to telescope to a collapsed orientation , so that the system 10 is allowed to slide up to the truck frame unrestricted , as shown in fig3 . the anti - rotation locking system then restricts the system 10 from moving away from the truck frame 30 . in normal operation of the trailer , the anti - rotation lock is set in the ready position . the anti - rotation locking mechanism has no effect during normal operation of the trailer . in a direct impact , the anti - rotation lock provides no restriction to the system 10 sliding forward , allowing the anti - rotation arms 14 to contact the truck plate 34 . when the anti - rotation arms 14 have contacted the truck plate 34 , the locking mechanism 26 holds the system 10 in plate against the plate 34 . during an angled impact , when the system 10 slides forwardly , the anti - rotation arms 14 contact the frame 30 . the direction of the impact creates an angular moment , putting one of the anti - rotation arms 14 in compression and one in tension . the locking action restricts the rotation of the attenuator by placing the pintle hook attachment in tension . with the pintle hook attachment in tension , and one of the anti - rotation arms in compression , rotation of the attenuator is restricted . post impact , the lock can be easily released , allowing the system 10 to be moved back from the end structure of the truck . now with reference to fig8 - 10 , a crash attenuator unit 36 has been attached to the telescoping anti - rotation attachment system 10 . the unit 36 is attached to the backup frame 12 in known fashion . in the illustrated embodiment , the attenuator unit 36 is mounted on wheels 38 disposed on a standard axle assembly 40 , as shown . in preferred embodiments , the crash attenuator unit 36 is essentially the same as an existing scorpion tma available from the assignee traffix devices , inc . and shown and described in u . s . pat . no . 6 , 581 , 992 , already incorporated herein by reference . components of the crash attenuator unit 36 include a strut portion 42 and a cartridge portion 44 . the strut portion 42 comprises a frame 46 , preferably comprised of aluminum tubing , and the cartridge portion 44 comprises a frame 48 , also comprised of aluminum tubing . energy absorbent cartridges 50 , 52 , and 54 are disposed within the unit 36 . fig1 and 12 are somewhat similar to fig2 and 3 , in that they illustrate a pre - impact condition position for the inventive system 10 , in fig1 , and a post - impact condition position for the inventive system , in fig1 , in somewhat more detail than is shown in fig2 and 3 . in particular , in this embodiment , larger anti - rotation support pads 18 are shown than in the fig2 and 3 embodiment , which provides a better support contact between the system 10 and the stop plate 34 . fig1 - 15 illustrate a somewhat modified embodiment of the present invention , wherein an arrowboard 56 has been installed on the crash attenuator unit 36 , specifically on the backup frame 12 . the arrowboard unit 56 includes support posts 58 which engage the back up frame to mount the arrowboard 56 onto the crash attenuator . this embodiment is also different , in that the wheels 38 and axle assembly 40 are disposed in the rear of the unit 36 , rather than the center thereof . this embodiment offers some advantages , in that it makes the unit simpler , lighter , more stable , and easier to produce . still another modified embodiment , of the telescoping anti - rotation attachment system 10 , is illustrated in fig1 . this embodiment features a single point attachment between the tma and the host vehicle , as in previous embodiments , by means of a ring hook 60 or the like , suitable for attachment using a conventional hitch system or other desired means . aft of the ring hook 60 are a plurality of telescoping sliders 62 , which function to collapse upon vehicular impact with the tma , in order to prevent rotation of the trailer ( tma ) upon impact . this embodiment differs from that shown in the prior embodiments , for example , in that the center support tongue 64 for supporting the ring 60 is rigid , rather than telescoping , as in the prior embodiment . on the other hand , the two supports 62 are telescoping , rather than rigid , as in the prior embodiment . the important concept is that , in either embodiment , there is a single - point connection between the tma and the vehicle , in conjunction with structure to prevent rotation of the tma upon impact by a vehicle . within this parameter , the structure may include one or more slides , one or more telescoping tubes , and / or one or more collapsing tubes , used in conjunction with one or more stops that move into contact with the host vehicle , in order to resist rotation of the trailer attenuator . some of the advantages of the present invention , and , particularly , these additional embodiments , are that it can be used in connection with a lighter host vehicle than the federal standard 19 , 600 lb . host vehicle currently necessary for tma &# 39 ; s . the inventors have determined that the present invention may successfully be used with a host vehicle as light as 10 , 000 lb , and perhaps lighter . the rams prevent rotation of the trailer with respect to the host vehicle . a torsion axle is preferably employed instead of leaf springs . the embodiments with rear - mounted wheels allow for elimination of a relatively incompressible center axle accordingly , although an exemplary embodiment of the invention has been shown and described , it is to be understood that all the terms used herein are descriptive rather than limiting , and that many changes , modifications , and substitutions may be made by one having ordinary skill in the art without departing from the spirit and scope of the invention .	6
referring to the drawings , fig1 schematically illustrates a method for directing lubricating material through an automatic planetary transmission to sufficiently cool the pinion gears of the planetary carrier . first , the lubricating material ( oil or other reasonably appropriate transmission fluids ) is supplied to the transmission at step 110 through an inlet on the exterior of the transmission housing where the lubricating material is then directed from the supply to the inner diameter of the main shaft at step 112 . next , the lubricating material is directed from the main shaft to the interior of the sun gear shaft at step 114 where the oil travels along the sun gear and its neighboring components . from the sun gear the oil is directed to the spider section of the planetary carrier at step 116 . the planetary carrier , being configured with machined and formed grooves , receives the lubricating material and directs the lubricating material into the grooves of the spider section at step 118 . next , the oil is directed into the axial slots ( 56 shown in fig1 and 3 ) of the first thrust washer ( 50 ) at step 120 . from the first thrust washer the lubricating material is directed axially and radially to the pinion bearings and the spindle of the pinion gear to specifically cool that area of the planetary carrier at step 122 . the oil is then directed to a second thrust washer ( 62 ) at step 124 , which directs the oil axially through axial slots 56 in the thrust washer to the flange section ( 28 shown in fig1 , 4 a and 4 b ) of the planetary carrier at step 126 . the oil is then directed radially outward , at step 127 , through grooves ( 65 shown in fig4 a ) in the flange section 28 . finally , the oil is dispersed to components adjacent to the planetary carrier ( 16 ) at step 128 and directed back to the sump ( or supply ) to repeat the process at 112 . the lubricating material 10 is directed through the transmission by pressurizing the inner cavity of the transmission . in the preferred embodiment , a pump ( not shown ) sends the lubricating material 10 , as shown in fig2 , from a source at 30 p . s . i . to the inner diameter of the main shaft 12 . to maintain the desired pressure level , the transmission components are designed to nest substantially close with respect to each another . this significantly seals the connection between the components and prevents the lubricating material 10 from flowing in unintended areas . for example , in fig2 , the sun gear 14 — adjacent to the planetary carrier 16 — rests on a bushing 18 and steel sleeve 20 that substantially prevent the lubricating material 10 from flowing away from the planetary carrier 16 . therefore , the bushing 18 and steel sleeve 20 help to maintain the desired pressure level in the vicinity of the planetary carrier 16 so that the lubricating material 10 can successfully reach the pinion bearings 22 of the pinion gears 24 . the planetary carrier 16 consists of at least one pinion gear 24 ( three of the five are shown in fig4 b ) and a two - piece housing defined by a spider section 26 and a flange section 28 which are sintered brazed together . the face of the spider section 26 of the planetary carrier 16 is shown in fig4 c . the spider section 26 contains cylindrical openings 29 to receive posts 30 which add stiffness and strength to the planetary carrier 16 to react the pinion bearing 22 loading . fig4 a shows the face of the flange section 28 , which is the more frontward portion of the planetary carrier 16 . the flange section 28 contains splines 32 , which connect the planetary carrier 16 to the main shaft 34 , as shown in fig2 , and transmit power to the rear of the transmission ( not shown ). as shown in fig2 , the planetary carrier 16 is designed so that the pinion gears 24 are in a drivable relationship with a sun gear 14 and ring gear 36 . together , the three gear types ( 14 , 24 and 36 ) encircle the main shaft 34 of the transmission and through engagement with clutches ( not shown ) determine the output speed of the transmission . one technical advantage of this invention is in the redesign of the spider section 26 and flange section 28 of the planetary carrier 16 . the spider section 26 of the planetary carrier 16 has five grooved areas , each having a first and second groove formed therein ( 38 and 40 respectively ). the grooves 38 , 40 have several functions including , directing the lubricating material 10 from the inner diameter of the planetary carrier 42 to the pinion bearings 22 at the inner diameter of the pinion gears 44 . each first groove 38 , as shown in fig4 c , is concave , facing the inner diameter of the planetary carrier 42 so as to receive lubricating material 10 from the sun gear 14 and sun gear shaft 15 . the first groove 38 is also segmentally annular , extending about the inner diameter of the planetary carrier 42 in each first groove . the first groove 38 is intersected by a second groove 40 , which extends radially to intersect the first groove 38 and radially along the grooved spider section 26 of the planetary carrier 16 to transfer the lubricating material 10 into a first pocket 46 . in the preferred embodiment , the second groove 40 is formed in the spider section 26 of the planetary carrier 16 by an alteration to the die ( not shown ) of the planetary carrier 16 . formed by a powder metallurgy process , the planetary carrier 16 is constructed with a die having a protrusion defining the second formed groove 40 . powder metallurgy was chosen because the process is ideal for parts with irregular curves or for small recesses that are difficult to machine . moreover , the process reduces the amount of material waste since the intricacies of the part can be included in the die instead of being sculpted from a blank through a series of machining processes . still , powder metallurgy has its limitations . the intricacies of the die must be such that the part is removable from the die . for this reason , in the preferred embodiment , the first groove 38 was machined into the spider section 26 of the planetary carrier 16 . the first groove 38 was designed to intersect the second groove 40 ( as shown in fig4 c ) and transfer the lubricating material 10 radially into the first pocket 46 where a first thrust washer 50 will aid in directing the lubricating material 10 into the pinion bearings 22 . the intersection between the first groove 38 and second groove 40 forms a shoulder at 52 , which acts as a dam to substantially prevent oil from escaping the pinion area of the spider section 26 of the planetary carrier 16 . the second groove 40 leads to and defines the first pocket 46 that extends radially to the inner diameter the pinion gear 44 where an axial slot 56 in the first thrust washer 50 receives the lubricating material 10 . adjacent to the first pocket 46 is the first thrust washer 50 , which is better shown in fig3 . the first thrust washer 50 has radially extending slots 54 ( or conned depressions ) spanning across the face of the first thrust washer 50 . the radially extending slots 54 in the first thrust washer 50 serve to direct the lubricating material 10 toward the first pocket 46 , as shown in fig2 . in the preferred embodiment , the thrust washer 50 also has axial slots 56 ( or notches ), shown in fig2 and 3 , which , along with groove 40 , carry the lubricating material 10 to the spindle 58 and bearings 22 of the pinion gear 24 where the spindle 58 is supported or press fit into the carrier bore 59 . moreover , the first thrust washer 50 also has a flanged edge 60 . the flanged edge 60 extends axially into the radially extending flange slots 61 of the spider section 26 and functions to keep each washer from rotating with respect to the spider section 26 of the planetary carrier 16 by nesting in the spider section 26 at 61 ( as shown in fig2 and 4 c ). from the first thrust washer 50 , the lubricating material 10 is directed to the pinion bearings 22 . the pinion bearings 22 , as shown in fig2 , are aligned axially along the spindle 58 . the pinion bearings 22 act to provide support for the pinion gear 24 . since the pinion gears 24 are in a drivable relationship with the ring gear 36 as well as the sun gear 14 , the pinion bearings 22 see a substantial amount of loading during operation of the transmission . therefore , this area requires lubrication for cooling to enhance the lifecycle of the pinion bearings 22 . also shown in fig2 , a second thrust washer 62 is attached to the pinion gear 24 . each second thrust washer 62 has radially and axially extending slots similar to 54 and 56 shown in fig3 . the slots of the second thrust washer 62 are operative to direct the lubricating material 10 axially away from the spindle 58 of the pinion gear 24 through axial slot 56 and towards a third groove 64 formed in the flanged section 28 of the planetary carrier 16 . the second thrust washer 62 also has a flanged edge 60 which nests in the flange section 28 at 65 ( as shown in fig4 a ). from each third groove 64 , the lubricating material 10 exits the planetary carrier 16 and is directed to other transmission components ( not shown ) for cooling and is eventually returned to the transmission sump for reuse . the configuration of transmission components adjacent to the planetary carrier 16 also assists in directing the lubricating material 10 to the spider section 26 of the planetary carrier 16 and into the pinion bearings 22 . the sun gear shaft 15 for example , which encircles the main shaft 34 , has at least one radially extending aperture 68 to direct the lubricating material 10 from the inner diameter of the main shaft 12 to the sun gear 14 and eventually the spider section 26 of the planetary carrier 16 . the sun gear shaft 15 is attached to the sun gear 14 by a section of splines 70 between the sun gear 14 and sun gear shaft 15 . the sun gear 14 is adjacent to a thrust bearing 72 , which further restricts the passage of the lubricating material 10 away from the planetary carrier 16 and its pinion gears 24 . moreover , the main shaft 34 is fitted with apertures like 74 that extend radially and direct the lubricating material 10 from the inner diameter of the main shaft 12 to the outer diameter of the main shaft 76 . the apertures — 68 and 74 — are designed to be large enough to permit the passage of the lubricating material 10 but small enough to maintain the pressure in the cavity of the planetary carrier 16 . lastly , the ring gear 36 also has a radially extending aperture 78 to permit the lubricating material 10 to exit the planetary carrier 16 . while the best modes for carrying out the invention have been described in detail , those familiar with the art to which this invention relates will recognize various alternative designs and embodiments for practicing the invention within the scope of the appended claims .	5
reference will now be made in detail to the present preferred embodiments of the invention , examples of which are illustrated in the accompanying drawings . wherever possible , the same reference numbers are used in the drawings and the description to refer to the same or like parts . fig2 is a diagram showing the circuit structure of a scanner according to one preferred embodiment of this invention . as shown in fig2 , the scanning circuit 200 is responsible for controlling the entire process of scanning a document . the scanning circuit 200 includes a main circuit module 210 and an optical sensor circuit module 220 . the main circuit module 210 and the optical sensor circuit module 220 are linked together through a connection cable 230 such as a flat cable . the flat cable carries both scan control signals and digital image data . the main circuit module 210 further includes a main control logic unit 270 , a memory unit 280 and a memory control logic unit 275 . the optical sensor circuit module 220 further includes an optical sensor 240 , an analog front - end processor ( afe ) 250 , an analog / digital converter 260 and a timing signal generator 265 . the main control logic unit 270 in the main circuit module 210 connects with the human / machine interface of a personal computer ( not shown ) through a communication interface 285 . here , the communication interface 285 can be a universal serial bus ( usb ) interface or an enhanced parallel port ( epp ) interface , for example . the communication interface 285 receives important scanning instructions regarding image resolution , brightness level and scanning range and converts the scanning instructions into scanning control signals that pass along the connection cable 230 . when the optical sensor circuit module 220 receives scanning control signals from the main circuit module 210 , the timing generator 265 produces the required timing control signals for extracting an analog image signal from the optical sensor 240 . the optical sensor 240 is a charge - coupled device ( ccd ) or a cmos image sensor , for example . the captured analog image signal is preprocessed by the analog front - end preprocessor 250 . thereafter , the pre - processed analog image is transmitted to the analog / digital converter 260 and converted to digital image data . the digital image data is subsequently transmitted to the main circuit module 210 through the connection cable 230 . at this moment , the data transmitted on the connection cable 230 is no longer the analog signal that easily has the distortion but is the digital image data that can be easily transmitted in a fast speed . as a result , it can effectively solve the issue about difficulty on maintaining the scanning quality when the scanning process is operated in the fast speed . on receiving the digital image data , the main circuit module 210 transfers the data to the memory unit 280 via the memory controller 275 . the memory unit 280 may contain conventional types of memory such as synchronous or non - synchronous dynamic random access memory ( dram ) or static random access memory ( sram ). obviously , the main control logic unit 270 may incorporate an image preprocessor ( not shown ) for compensating and adjusting the captured digital image data so that the scanned image can have better quality . in addition , timing signals may have to be adjusted due to the change in connection between the communication interface of various integrated circuits ( ics ). 1 . since the flat cable transmits digital data instead of easily distorted analog image signals , a clearer image can be obtained at a higher scanning speed . 2 . since the flat cable transmits scanning control signals between conventional ic communication interfaces instead of timing control signals , the effect due to electromagnetic interference is greatly minimized . it will be apparent to those skilled in the art that various modifications and variations can be made to the structure of the present invention without departing from the scope or spirit of the invention . in view of the foregoing , it is intended that the present invention cover modifications and variations of this invention provided they fall within the scope of the following claims and their equivalents .	7
fig1 shows a typical wellhead structure that is used in connection with an oil and / or gas well , where a wellhead 1 , at its upper end , is connected to a riser 2 which extends between a floating structure ( not shown ), for example , a platform or the like , and the wellhead 1 . a first casing 3 extends a distance down into a surface formation and is cemented to the surface formation o . the upper end of the first casing 3 is suitably suspended from the wellhead 1 , sealing devices 4 in the form of one or more packers being arranged between an exterior surface of the first casing 3 and an interior surface of the pressurised housing h of the wellhead 1 . within the first casing 3 there is arranged another , second casing 5 , which will then extend through the first casing 3 and a longer distance down into the surface formation o than the first casing 3 . the second casing 5 will , like the first casing 3 , be cemented to the surface formation o . the second casing 5 will in addition be partly supported by ( suspended in ) the first casing 3 . in order to obtain a tight connection between an interior surface of the first casing 3 and the exterior surface of the second casing 5 , sealing devices 4 are provided between the first and the second casing 3 , 5 . as the second casing 5 has a smaller diameter than the first casing 3 , a space will be formed between the first and the second casing 3 , 5 , which space is called an annulus . the space that is delimited by the interior surface of the first casing 3 , the second casing 5 and the casing hanger in the first and the second casing 3 , 5 will define a first annulus a . as described above for the first and the second casing 3 , 5 , a third casing 6 will run internally through the second casing 5 , and will be supported by ( suspended in ) the second casing 5 . the third casing 6 will have a diameter that is smaller than the diameter of the second casing 5 . here , the second and the third casing 5 , 6 , together with the casing hanger in the second and the third casing 5 , 6 , will define a second annulus b . within the third casing 6 there is arranged a last and fourth casing 7 , through which fourth casing 7 a production tubing ( not shown ) will run when the oil and / or gas well is in production . the fourth casing 7 will have a diameter that is smaller than the diameter of the third casing 6 . the space that is formed between the third and the fourth casing 6 , 7 and the casing hanger in the third and the fourth casing 6 , 7 will form a third annulus c . to obtain a tight connection between an interior surface of the second and the third casing 5 , 6 and the exterior surface of the third and the fourth casing 6 , 7 , sealing devices 4 are provided between the second and the third casing 5 , 6 and the third and the fourth casing 6 , 7 . the wellhead 1 may furthermore be connected to a blow - out valve ( not shown ), a so - called bop ( blow out preventer ). the above wellhead structure will provide a fluid and pressure - tight system , but conditions in the oil and / or gas well might mean that the sealing devices 4 , owing , for example , to large pressure build - ups in the well , temperature variations , or their service life , might begin to “ leak ”, such that a pressure leak occurs in the well , where this is not desirable . in order to prevent such undesired pressure leaks , a plurality of apparatus for measuring different parameters 8 , which will be explained in more detail in connection with remaining fig2 to 4 , will be arranged along the length of the wellhead 1 , such that measurement and monitoring of different parameters , for example , pressure and / or temperature , can be carried out in each of the annuli a - c in the well . the wellhead 1 will then be configured with a plurality of through holes ( not shown ), to which holes the apparatus 8 can suitably be connected . the measurements made in each of the annuli a - c may be suitably transmitted to , for example , a floating structure for processing and monitoring . fig2 shows a first embodiment of a measuring or monitoring apparatus 8 according to the present invention , where the apparatus 8 is shown partly from the side and in a cross - section , when connected to the wellhead 1 . the wellhead 1 will then be configured with a plurality of through holes or passages , 9 , which passages 9 will then be so positioned as to lead in to each of the annuli a - c . the apparatus 8 comprises a sensor 10 and a flange assembly 11 , which are fixedly connected to each other . the flange assembly 11 is constituted of a front flange portion 12 and a rear flange portion 13 , which via a plurality of bolts 14 or the like are connected to each other . an end of the rear flange portion 13 will then be so configured that it overlaps an end of the front flange portion 12 when the front and the rear flange portion 12 , 13 are assembled . both the front and the rear flange portion 12 , 13 will furthermore be configured with a groove or recess 16 , in which recess 16 an o - ring 17 is arranged when the front and the rear flange portion 12 , 13 are connected to each other , so as to provide a fluid - tight connection between them . the flange assembly 11 is further configured with a through bore 14 , in which bore 14 the sensor 10 and the associated electronics 15 are arranged . a second end ( opposite the end that is connected to the rear flange portion 13 ) of the front flange portion 12 will then be configured with a contact face 18 for the sensor 10 , the said contact face 18 forming a stop edge for the sensor 10 . the sensor 10 will then similarly be configured with a face 19 that will bear against the contact face 18 in the front flange portion 12 , such that the sensor 10 is positioned correctly in relation to the wellhead 1 . the sensor 10 will furthermore , along a part of its length , be configured with a threaded portion 20 , such that the sensor 10 can be screwed into the passage 9 in the wellhead 1 . the passage 9 in the wellhead 1 will then be configured with a complementarily threaded portion ( not shown ). the sensor 10 comprises a first electronic circuitry , e . g . in the form of an electronic printed circuit board 21 , which via wires 22 is connected to a second electronic circuitry in the form of a separate main printed circuit board 23 arranged in the bore 14 in the front flange portion 12 . through this configuration , the sensor 10 , comprising the electronic printed circuit board 21 , will be separated from the main printed circuit board 23 , the sensor 10 being arranged at the end of the front flange portion 12 which lies closest to the wellhead 1 , whilst the separate main printed circuit board 23 will be arranged at an opposite end of the front flange portion 12 , adjacent to the rear flange portion 13 . between the sensor 10 and the separate main printed circuit board 23 there is disposed a pressure - tight element 24 , for instance a ceramic element with wires 22 connecting the sensor 10 and the separate main printed circuit board 23 extending through the ceramic element . in one embodiment , the wires 22 will , however , not run through the whole of the ceramic element 24 , only a certain length into the ceramic element 24 , such that wires 22 from sensor 10 and wires 22 to the main printed circuit board 23 , when arranged in the ceramic element 24 , will be located at a distance from each other . the ceramic element 24 is however so configured that through at least one through - going portion or area through the ceramic element 24 there is arranged a mixture of a ceramic material and an electrically conducting material ( for example , platinum ). this will mean that the ceramic element 24 will form a pressure - tight barrier in the apparatus 8 . the ceramic element 24 is in a fluid and / or pressure - tight way connected to a sleeve 25 . the sleeve 25 is further configured with a threaded portion ( not shown ) and a varying cross - section along its length . the current passage through the ceramic element 24 may however be achieved by , for example , using metallic or other electrically conducting materials . the pressure - tight element 24 has been described above , by example , as a ceramic element . in this case the pressure - tight element 24 may be provided as a ceramic feedthrough disc , wherein wires or other electrical conductors may be embedded in the ceramic element . the ceramic material may be chrystalline or non - chrystalline . the ceramic material may , e . g ., include aluminium oxide . alternatively , the pressure - tight element 24 may be a glass element , or as another alternative , the pressure - tight element 24 may include a metallic disc ( e . g ., made of steel or titanium ), and the transmission devices may be electrical conductors ( e . g ., made of platinum ) passed through bores in the metallic disc . further , a glass , sapphire or a ceramic material may surround each conductor and fluidly seal the space between each conductor and the corresponding bore in the metallic disc . the pressure - tight element 24 may be located in a portion of the bore 14 where the diameter is reduced . the pressure - tight element 24 is shown fitted into a portion of the bore having a diameter corresponding to the diameter of the pressure - tight element 24 . a sleeve 25 is located in the bore 14 in engagement with a first side of the pressure - tight element facing the passage 9 . the sleeve 25 in this position exerts pressure to the isolation element 24 . the sleeve may be configured with threads , provided for engagement with threads in the bore 14 , and may be provided with a diameter enlarged portion 25 b arranged to fit with a restriction of the bore 14 which may provide an end stop for the sleeve 25 . by engaging the threads of the sleeve 25 with the threads of the bore 14 , the sleeve may be screwed into a position exerting a pressure to the pressure - tight element 24 . a second side of the isolation element 24 , which faces away from the passage 9 , rests against a restriction in the diameter of the bore providing a contact portion 26 . in between the contact portion 26 and a portion of the second side of the isolation element a seal , for instance a metallic seal , may be provided . by moving the sleeve 25 relative to the bore 14 , for instance by screwing the sleeve 25 relatively to the bore 14 the isolation element 24 exerts a force to the seal of a size which provides an isolation engagement between the contact portion 26 , the seal and the isolation element 24 . this arrangement may enable or further improve the pressure tight properties of the apparatus . the through bore 14 in the front flange portion 12 will along a part of its length be configured with a varying cross - section , which varying cross - section will be complementarily configured with the varying cross - section of the sleeve 25 . a rear edge 26 of the varying cross - section in the through bore 14 will , when the sleeve 25 with the pressure - tight element 24 , e . g . ceramic element , is arranged in the varying cross - section of the through bore 14 , together with an end of the sleeve 25 , form a tight connection between the front flange portion 12 and the sleeve 25 . this arrangement may form a fireproof connection in the apparatus 8 . the rear flange portion 13 is configured with a through and threaded hole 27 , so as to enable a cable lead - in 28 , comprising a tensioning nut 29 , to be connected to the threaded hole 27 . between the contact faces of the rear flange portion 13 and the cable lead - in 28 there is arranged a seal 30 in the form of an o - ring . an electric cable e is then passed through the cable lead - in 28 and connected to a connecting printed circuit board 31 in the though bore 14 in the flange assembly 11 . the separate main printed circuit board 23 and connecting printed circuit board 31 are , by means of a securing device 32 , connected to a rear wall 33 of the front flange portion 12 . the securing device 32 will further ensure that the main printed circuit board 23 and the connecting printed circuit board 31 are arranged at a distance from each other . signals received from the sensor 10 will then be wirelessly transmittable from the main printed circuit board 23 to the connecting printed circuit board 31 , in order thus , through the electric wire e , to be transmitted for processing on a floating structure ( not shown ). the rear flange portion 13 , which is an “ open ” sleeve , is , at an end opposite the end overlappingly connected to the front flange portion 12 , configured for being connected to an end termination 34 , such that the apparatus 8 can be closed or sealed at the end opposite the connection to the wellhead 1 . the end termination 34 is then configured with a plurality of through openings 35 , which through openings 35 are used for passage of bolts 36 . an end termination in the rear flange portion 13 will then be configured with a plurality of threaded holes 37 for receipt and screw fastening of bolts 36 . the end termination 34 will on one side be configured with a projection 38 , which projection 38 will be such that it essentially corresponds to the through bore 14 , such that the projection 38 will extend a certain distance into the rear flange portion 13 when the end termination 34 , via the bolts 36 , is connected to the rear flange portion 13 . a seal 39 in the form of an o - ring is arranged between the interior surface of the rear flange portion 13 and the exterior surface of the projection 38 , one or both of these surfaces then being configured with a groove for receiving the seal 39 . furthermore , the front flange portion 12 , in a face a which forms contact with the wellhead 1 , is configured with a plurality of holes 41 , such that bolts and nuts 42 can be used to fixedly connect the apparatus 8 to the wellhead 1 . face a is further configured with a recess 43 for receiving a sealing element 44 such that a tight connection is provided between the apparatus 8 and the wellhead 1 when they are connected to each other . fig3 shows another embodiment of the apparatus 8 according to the present invention , where the apparatus 8 is now configured so as to be able to transmit signals from the sensor 10 wirelessly . with the exception of how the transmission of signals takes place according to this embodiment , the general component composition of the apparatus 8 and its operating principle are the same as described for the first embodiment of the invention as shown in fig2 , and so for the sake of simplicity they are not described again . the embodiment shown in fig3 uses a wireless transmission of signals from the sensor 10 , where the rear flange portion 13 will be configured with a through and threaded hole 27 , so as to enable a wireless antenna 44 to be connected to the through and threaded hole 27 . a securing device 32 is also used in this embodiment to connect the separate main printed circuit board 23 and the connecting printed circuit board 31 to the rear wall 33 of the front flange portion 12 . however , the distance between the main printed circuit board 23 and the connecting printed circuit board 31 will now be greater than in the embodiment described with reference to fig2 , seen in relation to the fact that a part of the wireless antenna 44 will extend a distance into the through bore 14 in the flange assembly 11 . signals received from the sensor 10 will then be wirelessly transmittable from the main printed circuit board 23 to the connecting printed circuit board 31 , so as to be further transmittable wirelessly from the connecting printed circuit board 31 to the wireless antenna 44 , in order to be further transmitted wirelessly for processing on a floating structure ( not shown ). for signal amplification , a plurality of signal amplifying units ( not shown ) may be provided between the wellhead and the floating structure . to operate the sensor 10 and / or the wireless antenna 44 in the apparatus 8 , a battery or a battery pack 45 is provided in the apparatus 8 when the apparatus 8 is assembled . this embodiment will mean that the battery or battery pack 45 can easily be replaced by unscrewing bolts 36 in the end termination 34 and removing the end termination 34 from the rear flange portion 13 . the battery or battery pack 45 can in a suitable manner , for example , by means of wires etc . ( not shown ), be connected to the connecting printed circuit board 31 . the battery or battery pack 45 may also be connected to , or comprise a device ( not shown ) capable of ensuring that the battery or battery pack 45 is turned off and on at certain time intervals . the device can then turn the battery or battery pack 45 on for a pre - specified time unit ( minutes , hours or days ), so as to allow the desired number of measurements of , for example , pressure and temperature to be carried out , after which the device will turn the battery or battery pack 45 off . however , it should be understood that such a device must also comprise the possibility of being overridden , seen in relation to the fact that measurements with the apparatus 8 may also be carried out outside the pre - specified time units . fig4 shows an additional embodiment of the apparatus 8 according to the present invention , where the rear flange portion 13 in the apparatus 8 is configured with several through and threaded holes 27 . the general component composition of the apparatus 8 and its operating principle are the same as described for the first embodiment of the invention as shown in fig2 , and so for the sake of simplicity they are not described again . configuring the rear flange portion 13 with several through and threaded holes 27 , will enable the apparatus 8 to be connected to two electric cables e , an electric cable e and a wireless antenna 44 , or even two wireless antennas 44 . alternatively , one of the through and threaded holes 27 can initially be closed by a stop plug 46 . if , for example , the electric wire e or the wireless antenna 44 for some reason is knocked off or damaged there will be the possibility of connecting to the apparatus 8 by removing the stop plug 46 and , for example , coupling a wireless antenna 44 to the other through and threaded hole 27 . in addition , this embodiment will also permit several similar apparatus to be connected on the same line , where the apparatus will then be able to communicate with each other digitally . the invention has now been explained by referring to some non - limiting examples . a person of skill in the art will understand that it will be possible to make a number of variations and modifications to the temperature and pressure monitoring system as described within the scope of the invention as defined in the attached claims .	4
here we describe an editing tool for affect in speech . we describe its architecture and an implementation and also suggest a set of transformations of f 0 contours , energy , duration and spectral content , for the manipulation of affect in speech signals . this set includes operations such as selective extension , shrinking , and actions such as ‘ cut and paste ’. in particular , we demonstrate how a natural expression in one utterance by a particular speaker can be transformed to other utterances , by the same speaker or by other speakers . the basic set of editing operators can be enlarged to encompass a larger variety of transformations and effects . we describe below the method , show examples of subtle expression editing of one speaker , demonstrate some manipulations , and apply a transformation of an expression using another speaker &# 39 ; s speech . the affect editor , shown schematically in fig1 , takes an input speech signal x , and allows the user to modify its conveyed expression , in order to produce an output signal { tilde over ( x )}, with a new expression . the expression can be an emotion , mental state or attitude . the modification can be a nuance , or might be a radical change . the operators that affect the modifications are set by the user . the editing operators may be derived in advance by analysis of an affective speech corpus . they can include a corpus of pattern samples for concatenation , or target samples for morphing . a complete system may allow a user to choose either a desired target expression that will be automatically translated into operators and contours , or to choose the operators and manipulations manually . the editing tool preferably offers a variety of editing operators , such as changing the intonation , speech rate , the energy in different frequency bands and time frames , or the addition of special effects . this system may also employ an expressive inference system that can supply operations and transformations between expressions and the related operators . another preferable feature is a graphical user interface that allows navigation among expressions and gradual transformations in time . the preferred embodiment of the affect editor is a tool that encompasses various editing techniques for expressions in speech . it can be used for both natural and synthesized speech . we present a technique that uses a natural expression in one utterance by a particular speaker for other utterances by the same speaker or by other speakers . natural new expressions may be created without affecting the voice quality . this system may also employ an expressive inference system that can supply operators and transformations between expressions and the related operators . another preferable feature is a graphical user interface that allows navigation among expressions and gradual transformations in time . the editor employs a preprocessing stage before editing an utterance . in preferred embodiments post - processing is also necessary for reproducing a new speech signal . the input signal is preprocessed in a way that allows processing of different features separately . the method we use for preprocessing and reconstruction was described by slaney ( slaney m ., covell m ., lassiter b . : automatic audio morphing ( icassp96 ), atlanta , 1996 , 1001 - 1004 ) who used it for speech morphing . it is based on analysis in the time - frequency domain . the time - frequency domain is used because it allows for local changes of limited durations , and of specific frequency bands . from human computer interaction point of view , it allows visualization of the changeable features , and gives the user graphical feedback for most operations . we also use a separate f 0 extraction algorithm , so a contour can be seen and edited . these features also make it a helpful tool for the psycho - acoustic research of features &# 39 ; importance . the pre - processing stages are described in algorithm 1 : 2 . calculating the smooth spectrogram using mel - frequency cepstral coefficients ( mfcc ). the coefficients are computed by re - sampling a conventional magnitude spectrogram to match critical bands as measured by auditory perception experiments . after computing logarithms of the filter - bank outputs , a low dimensional cosine transform is computed . the mfcc representation is inverted to generate a smooth spectrogram for the sound which does not include pitch . 3 . divide the spectrogram by the smooth spectrogram , to create a spectrogram of f 0 . 4 . extracting f 0 . this stage simplifies the editing of f 0 contour . 5 . edge detection on the spectrogram , in order to find significant patterns and changes , and to define time and frequency pointers for changes . edge detection can also be done manually by the user . the pre - processing stage prepares the data for editing by the user . the affect editing tool allows editing of an f 0 contour , spectral content , duration , and energy . different implementation technique can be used for each editing operation , for example : 1 . changing the intonation . this can be implemented by mathematical operations , or by using concatenation . another method for changing intonation is to borrow f 0 contours from different utterances of the same speaker and other speakers . the user may change the whole f 0 contour , or only parts of it . 2 . changing the energy in different frequency ranges and time - frames . the signal is divided into frequency bands that relate to the frequency response of the human ear . a smooth spectrogram that represents these bands is generated in the pre - processing stage . changes can then be made in specific frequency bands and time - frames , or over the whole signal . 3 . changing the speech rate . extend and shrink the duration of speech parts by increasing and decreasing the overlap between frames in the inverse short time fourier transform . this method works well for the voiced parts of the speech , where f 0 exists , and for silence . the unvoiced parts , where there is speech but no f 0 contour , can be extended by interpolation . these changes can be done on parts of the signal or on all of it . as will be shown below , operations on the pitch spectrogram and on the smooth / spectral spectrogram are almost orthogonal in the following sense . if one modifies only one of the spectrograms and then calculate the other from the reconstructed signal it will have minimal or no variations compared to the one calculated from the original signal . the editing tool has built - in operators and recorded speech samples . the recorded samples are for borrowing expression parts , and for simplifying imitation of expressions . after editing , the system has to reconstruct the speech signal . post - processing is described in algorithm 2 . 6 . regeneration of the new full spectrogram by multiplying the modified pitch spectrogram with the modified smooth spectrogram . 7 . spectrogram inversion , as suggested by griffin and lim [ 2 ]. algorithm 2 : post - processing for reconstruction of a speech signal after editing . spectrogram inversion is the most complicated and time - consuming stage of the post - processing . it is complicated because spectrograms are based on absolute values , and do not give any clue as to the phase of the signal . the aim is to minimize the processing time in order to improve the usability , and to give direct feedback to the user . this is just one example of many editing techniques that can be integrated in the speech editor tool , as provided for example by text and image processing tools . in this section we show some of the editing operations , with a graphical presentation of the results . we were able to determine that an affect editor is feasible with current technology . the goals were to determine whether we could obtain new speech signals that sound natural and convey new or modified expressions , and to experiment with some of the operators . we examined basic forms of the main desired operations , including changing f 0 contour , changes of energy , spectral content , and speech rate . for our experiment we used recordings of 15 people speaking hebrew . each speaker was recorded uttering repeatedly the same two sentences during a computer game , with approximately a hundred iterations each . the game elicited natural expressions and subtle expressions . it also allowed tracking of dynamic changes among consecutive utterances . fig2 presents features of the utterances ‘ sgor de - let ’ which means in hebrew ‘ close the door ’, uttered by a male speaker . fig2 a represents the fundamental frequency curves of two original utterances . the higher curve shows the expression of uncertainty , and the lower curve shows determination . the uncertainty curve is long , high , and has a mildly ascending slope , while the determination curve is shorter and has a descending slope . fig2 b represents the curve of the edited utterance of uncertainty , with the combined f 0 curve generated from the two original curves , after reconstruction of the new edited signal . the first part of the original uncertainty curve , between 0 . 25 sec and 0 . 55 sec , was replaced by the contour from the determination curve . the location of the transformed part and its replacement were decided using the extracted f 0 curves . the related parts from the f 0 spectrograms were replaced . a spectrogram of the new signal was generated by multiplying the new f 0 spectrogram by the original smoothed energy spectrogram . the combined spectrogram was then inverted . the energy and spectral content remained as in the original curve . this manipulation yields a new and natural - sounding speech signal , with a new expression , which is the intended result . we have intentionally chosen an extreme combination in order to show the validity of the editing concept . an end - user is able to treat this procedure similarly to ‘ cut and paste ’, or ‘ insert from file ’ commands . the user can use pre - recorded files , or can record the required expression to be modified . fig3 presents another set of operations , this time on the utterance ‘ ptach de - let zo ’, which means ‘ open door this ’ ( open this door ) in hebrew . we manipulated local features of the fundamental frequency , as shown . we took an utterance by a male speaker , and replaced part of its f 0 contour with a contour of an utterance by a female speaker with a different expression , using the same technique as in the previous example . the pitch of the reconstructed signal is shown in crosses . as can be seen , both the curve shape and its duration were changed . the duration was extended by inverting the original spectrogram with a smaller overlap between frames . the sampling rate of the recorded signals was 32 khz ; the short - time fourier transform , and the f 0 extraction algorithm used frames of 50 ms with original overlap of 48 ms , which allowed precision calculation of low f 0 and flexibility of duration manipulations . after changing the intonation , we took the edited signal and changed its energy by multiplying it by a gaussian , so that the center of the utterance was multiplied by 1 . 2 and the sides the beginning and the end of the utterance , were multiplied by 0 . 8 . the new signal sounds natural , with the voice of the male speaker . the new expression is a combination of the two original expressions . the goal here was to examine editing operators to obtain natural - sounding results . we employed a variety of manipulations , such as replacing parts of intonation contours with different contours from the same speaker and from another speaker , changing the speech rate , and changing the energy by multiplying the whole utterance by a time dependent function . the results were new utterances , with new natural expressions , in the voice of the original speaker . these results were confirmed by initial evaluation with hebrew speakers . the speaker was always recognized , and the voice sounded natural . on some occasions the new expression was perceived as unnatural for the specific person , or the speech rate too fast . this happened for utterances in which we had intentionally chosen slopes and f 0 ranges which were extreme for the edited voice . in some utterances the listeners heard an echo . this occurred when the edges chosen for the manipulations were not precise . using pre - recorded intonation contours and borrowing contours from other speakers enables a wide range of manipulations of new speakers &# 39 ; voices , and can add expressions that are not part of a speaker &# 39 ; s normal repertoire . a relatively small reference database of basic intonation curves can be used for different speakers . time - related manipulations , such as extending the shrinking durations , and applying time dependent functions , extend the editing scope even farther . the system allows flexibility and a large variety of manipulations and transformations and yields natural speech . gathering these techniques and more under one editing tool , and defining them as editing operators creates a powerful tool for affect editing . however , to provide a full system which is suitable for general use the algorithms benefit in being refined , especially synchronization between the borrowed contours and the edited signal . special consideration should be given to the differences between voiced ( where there is f 0 ) and unvoiced speech . usability aspects should also be addressed , including processing time . we have described a system for affect editing for non - verbal aspects of speech . such an editor has many useful applications . we have demonstrated some of the capabilities of such a tool for editing expressions of emotion , mental state and attitudes , including nuances of expressions and subtle expressions . we examined the concept using several operations , including borrowing f 0 contours from other speech signals uttered by the same speaker and by other speakers , changing speech rate , and changing energy in different time frames and frequency bands . we managed to reconstruct natural speech signals for speakers with new expressions . these experiments demonstrate the capabilities of this editing tool . further extensions could include provision for real - time processing input from affect inference systems and labeled reference data for concatenation , an automatic translation mechanism from expressions to operators , and a user interface that allows navigation among expressions . the method chosen for segmentation of the speech and sound signals into sentences was based on the modified entropy - based endpoint detection for noisy environments , described by shen ( zwicker , e ., “ subdivision of the audible frequency range into critical bands ( frequenzgruppen )”, journal of the acoustical society of america 33 . 248 , 1961 ). this method calculates the normalized energy in the frequency domain , and then calculates entropy , as minus the product of the normalized energy and its logarithm . in this way , frequencies with low energy get a higher weight . it corresponds to both speech production and speech perception , because higher frequencies in speech tend to have lower energy , and require lower energy in order to be perceived . in order to improve the location of end - points a zero - crossing rate calculation ( zwicker , e ., flottorp g . and stevens s . s ., “ critical bandwidth in loudness summation .” journal of the acoustical society of america 29 . 548 - 57 , 1957 ) was used at the edges of the sentences identified by the entropy - based method . it corrected the edge recognition by up to 10 msec in each direction . this method yielded very good results , recognizing most speech segments ( 95 %) for men but it requires different parameters for men and for women . the signal is divided into frames x of 512 samples each , with overlap of 10 msec . the length of overlap in frames is : overlap = 10e − 3 · f sampling the parameters that affect the sensitivity of the detection are : μ — the entropy threshold , and the overlap between frames . a speech segment is located in frames in which the entropy & gt ; entropy th . locate all short speech segment candidates and check if the can be unified with their neighbours . otherwise , a segment shorter than 2 frames is not considered a speech segment . a short segment of silence in the middle of a speech segment becomes part of the speech segment . check that the length of the segment is longer than the minimum sentence length allowed ; 0 . 1537 sec . define threshold of zero crossing as 10 % of the average zc : zc th = 0 . 1 · average ( zc ) for each of the identified speech segment , check if the there are adjacent areas in which zc & gt ; zc th . if there are , the borders of the segments move to the beginning and end as defined by the zero - crossing . psychological and psychoacoustic tests have examined the relevance of different features to the perception of emotions and mental states using features such as pitch range , pitch average , speech rate , contour , duration , spectral content , voice quality , pitch changes , tone base , articulation and energy level . the features most straightforward for automatic inference of emotions from speech are derived from the fundamental frequency , which forms the intonation , energy , spectral content , and speech rate . however additional features such as loudness , harmonies , ( jitter , shimmer and rhythm may also be used . jitter and shimmer are fluctuations in f 0 frequency and in amplitude respectively ). however the accuracy of the calculation of these parameters is highly dependent on the recording quality , sampling rate and the time units and frame length for which they are calculated . alternative features from a musical point of view are , for example , tempo , harmonies , dissonances and consonances ; rhythm , dynamics , and tonal structures or melodies and the combination of several tones at each time unit . other parameters include mean , standard deviation , minimum , maximum and range ( equals maximum - minimum ) of the pitch , slope and speaking rate , statistical features of pitch and of intensity of filtered signals . our preferred features are set out below : the central feature of prosody is the intonation . intonation refers to patterns of the fundamental frequency , f 0 , which is the acoustic correlate of the rate of vibrations of the vocal folds . its perceptual correlate is pitch . people use f 0 modulation i . e . intonation in a controlled way to convey meaning . there are many different extraction algorithms for the fundamental frequency . i examined two different methods for calculating fundamental frequency f 0 , here referred to as pitch , an autocorrelation method with inverse linear prediction code ( lpc ) and a cepstrum method . both methods of pitch estimation gave very similar results in most cases . paul boersma &# 39 ; s algorithm was used by him in the tool praat which in turn is used for emotions analysis in speech and by many linguists for research of prosody and prosody perception . this was adopted to improve the pitch estimation . paul boersma pointed out that sampling and windowing cause problems in determining the maximum of the autocorrelation signal . his method therefore includes division by the auto - correlation of the window , which is used for each frame . the next stage is to find the best time - shift candidates in the autocorrelation , i . e . the maximum values of the autocorrelation . different weight with strength , and given to voiced candidates and to unvoiced candidates . the next stage is to find an optimal sequence of pitch values for the whole sequence of frames , i . e . for the whole signal . this uses the viterbi algorithm with different costs associated with transitions between adjacent voiced frames and with transitions between voiced and unvoiced frames ( these weights depend partially on the shift between frames ). it also penalises transitions between octaves ( frequencies twice as high or low ). the third method yielded the best results . however , it still required some adaptations . speaker dependency is a major problem in automatic speech processing as the pitch ranges for different speakers can vary dramatically . it is often necessary to clarify the pitch manually after extraction . i have adapted the extraction algorithm to correct the extracted pitch curve automatically . the first attempt to adapt the pitch to different speakers included the use of three different search boundaries , of 300 hz for men , 600 hz for women and 950 hz for children , adjusted automatically by the mean pitch value of the speech signal . although this has improved the pitch calculations , the improvement was not general enough . the second change considers the continuity of the pitch curves . it comprises several observed rules . first , the maximum frequency value for the ( time shift ) candidates ( in the autocorrelation ) may change if the current values are within a smaller or larger range . the lowest frequency default was set to 70 hz , although automatic adaptation to 50 hz was added , for extreme cases . the highest frequency was set to 600 hz . only very few sentences in the two datasets required a lower minimum value , mainly men who found it difficult to speak ; a higher range , mainly children who were trying to be irritating . second the weights of the candidates are changed if using other candidates with originally lower weights can improve the continuity of the curve . several scenarios may cause such a change : first , frequency jumps between adjacent frames that exceed 10 hz : in this case candidates that offer smaller jumps should be considered . second , candidates exactly one octave higher or lower from the most probable candidate , with lower weights . in addition , in order to avoid unduly short segments , if voiced segments comprise no more than two consecutive frames , the weights of these frames are reduced . correction is also considered for voiced segments that are an octave higher or lower than their surrounding voiced segments . this algorithm can eliminate the need of manual intervention in most cases , but is time consuming . algorithm 4 describes the algorithm stage by stage . fig4 shows two fundamental frequency curves , one as extracted by the original algorithm of the praat , and the other with the additional modifications . another way used to describe the fundamental frequency at each point is to define one or two base values , and define all the other values according to their relation to these values . this use of intervals provides another way to code a pitch contour . divide the speech signal signal into overlapping frames y of frame length , framelength , which allows 3 cycles of the lowest allowed frequency · f s is the sampling rate of the speech signal . i also tried shifts of 1 , 2 and 10 msec . a shift of 5 msec gives a smoother curve than 1 msec and 2 msec , with less demands on memory and processing , while still being sufficiently accurate . ( the window specified in the original paper does not assist much , and should be longer than the length stated in the paper . it is not implemented in praat ). calculate c wn , the normalized autocorrelation of the window . c w is the autocorrelation of the window ; fft length was set to 2048 . b . c w = real ( ifft ( abs ( x w ) 2 )) short - term analysis . for each signal frame y of length framelength and step of frameshift calculate : 1 . subtract the average of the signal in a frame from the signal amplitude at each sampling point . y n = y − mean ( y ) 2 . apply a hanning window w to the signal in the frame , so that the centre of the frame has a higher weight than the boundaries . c a = real ( ifft ( abs ( x ) 2 )) 4 . normalize the autocorrelation function : 6 . find candidates for pitch from the autocorrelation signal — the first n max maxima values of the modified autocorrelation signal ; n was set to 10 . 7 . for each of the candidates , calculate parabolic interpolation with the autocorrelation points around it , in order to find more accurate maximum values of the autocorrelation . 9 . check if the candidates &# 39 ; frequencies are within the specified range , and their weight is positive . if not , they become unvoiced candidates , with value 0 . 10 . define the strength of a frame as the weight of the signal in the current frame relative to all the speech signal ( calculated at the beginning in the program ) calculate an optimal sequence of f 0 ( pitch ), for the whole utterance . calculating for every frame , and every candidate in each frame , recursively , using m iterations ; m = 3 . the cost for transition from voiced to voiced , and among octaves is : ii . calculate range , median , mean and standard deviation ( std ) for the extracted pitch sequence ( the median is not as sensitive as mean to outliers ). a . consider frequency jumps to higher or lower octaves ( f * 2 or f / 2 ), by equalizing the candidates &# 39 ; weights , if these candidates exist . b . if the best candidate creates a frequency jumps of over 10 hz , consider a candidate with jump smaller than 5 hz , if exists , by equalizing the candidates &# 39 ; weights . iv . adapt to speaker . change maxpitch by factor 1 . 5 , using the median , range and standard deviation of the pitch sequence : v . for very short voiced sequences ( 2 frames ), reduce the weight by half vi . if the voiced part is shorter than the n th part of the signal length then : ; n = 1 / 3 if equalize weights for consecutive voiced segments in the utterance , among which there is an octave jumps after m iterations , the expectation is to have a continuous pitch curve . in the second stage a more conservative approach was taken , using the bark scale with additional filters for low frequencies . the calculated feature was the smoothed energy , in the same overlapping frames as in the general energy calculation and the fundamental frequency extraction . in this calculation the filtering was done in the frequency domain , after the implementation of short - time fourier transform , using slaney &# 39 ; s algorithm ( slaney m ., covell m ., lassiter b . : automatic audio morphing ( icassp96 ), atlanta , 1996 , 1001 - 1004 . another procedure for the extraction of the fundamental frequency , which includes an adaptation to the boersma algorithm in the iteration stage ( stage 10 ), is shown in algorithm 5 below . 2 . apply a hamming window to the signal in the frame , so that the centre of the frame has a higher weight then the boundaries . 5 . find candidates for the pitch from the normalised autocorrelation signal — the first n maxima values . calculate parabolic interpolation with the autocorrelation points around it , in order to find more accurate maximum values of the auto correlation . keep all candidates for harmonic properties calculation algorithm 6 & gt ;& gt ;& gt ; calculate in iteration an optimal sequence of f 0 ( pitch ), for the whole utterance . calculate for every frame , and every candidate in each frame , recursively , using the viterbi algorithm . in each iteration , adjust the weights of the candidates according to : 6 . check if the candidates &# 39 ; frequencies are within the specific range , and their weights are positive . if not , they become unvoiced candidates , with frequency value 0 . 7 . define the strength as the relation between the average value of the signal in the frame and the maximal value of the entire speech signal . calculate weights according to pre - defined threshold values and frame strengths for voiced and unvoiced candidates . 8 . the cost for transition from voiced to unvoiced or from unvoiced to voiced . 9 . the cost of transition from voiced to voiced , and among octaves 10 . the continuity of the curve ( adaptations to boersma &# 39 ; s algorithm ): the adaptation is achieved by adapting the strength of a probable candidate to the strength of the leading candidate . a . avoid frequency jumps to higher or lower octaves b . frequency changes greater than 10 hz c . eliminate very short sequences of either voiced or unvoiced signal . d . adapt to speaker by changing the allowed pitch range . & gt ;& gt ;& gt ; after m iterations , the expectation is to have a continuous pitch curve . referring again to fig4 the upper pitch extraction has ringed regions indicating outliers that require correction , the lower is after modification using algorithm 5 . the second feature that signifies expressions in speech is the energy , also referred to as intensity . the energy or intensity of the signal x for each sample i in time is : the smoothed energy is calculated as the average of the energy over overlapping time frames , as in the fundamental frequency calculation . if x1 . . . xn defines the signal samples in a frame then the smoothed energy in each frame is ( optionally , depending on the definition , this expression may be divided by frame_length ): the first analysis stage considered these two representations . in the second stage only the smoothed energy curve was considered , and the signal was multiplied by a window so that in each frame a larger weight was given to the centre of the frame . this calculation method yields a relatively smooth curve that describes the more significant characteristics of the energy throughout the utterance ( w i denotes the window ; optionally , depending on the definition , this expression may be divided by frame_length ): another related parameter that may also be employed is the centre of gravity : referring to fig5 this shows a speech signal and the results of different energy calculations ; the speech signal is shown in ( a ), its energy ( b ), the smoothed energy ( averaged ) ( c ) and smoothed energy with a window ( d ). it can be seen that the smooth curves ( c and d ) give the general behaviour of the energy , or the contour of the energy , rather than rapid fluctuations that are more sensitive to noise , as in the energy calculation for each sample ( b ). the application of a window ( d ), emphasises the local changes in time , and follows more closely the original contour , as of the signal itself ( a ). features related to the spectral content of speech signals are not widely used in the context of expressions analysis . one method for the description of spectral content is to use formants , which are based on a speech production model . i have refrained from using formants as both their definition and their calculation methods are problematic . they refer mainly to vowels and are defined mostly for low frequencies ( below 4 - 4 . 5 khz ). the other method , which is the more commonly used , is to use filter - banks , which involves dividing the spectrum into frequency bands . there are two major descriptions of frequency bands that relate to human perception , and these were set according to psycho - acoustic tests — the mel scale and the bark scale , which is based on empirical observations from loudness summation experiments ( zwicker , e . “ subdivision of the audible frequency range into critical bands ( frequenzgruppen )”, journal of the acoustical society of america 33 . 248 , 1961 ; zwicker , e ., flottorp g . and stevens s . s . “ critical bandwidth in loudness summation .”, journal of the acoustical society of america 29 . 548 - 57 , 1957 ). both correspond to the human perception of sounds and their loudness , which implies logarithmic growth of bandwidths , and a nearly linear response in the low frequencies . in this work , the bark scale was chosen because it covers most of the frequency range of the recorded signals ( effectively 100 hz - 10 khz ). bark scale measurements appear to be robust across speakers of differing ages and sexes , and are therefore useful as a distance metric suitable , for example , for statistical use . the bark scale ranges from 1 to 24 and corresponds to the first 24 critical bands of hearing . the subsequent band edges are ( in hz ) 0 , 100 , 200 , 300 , 400 , 510 , 630 , 770 , 920 , 1080 , 1270 , 1480 , 1720 , 2000 , 2320 , 2700 , 3150 , 3700 , 4400 , 5300 , 6400 , 7700 , 9500 , 12000 , 15500 . the formula for converting a frequency f ( hz ) into bark is : in this work , at the first stage , 8 bands were used . the bands were defined roughly according to the frequency response of the human ear , with wider bands for higher frequencies up to 9 khz . fig6 shows the energy in different bands of a speech signal using the eight bands . in the second stage the bark scale up to 9 khz was used . one of the parameters of prosody is voice quality . we can often describe voice with terms such as sharp , dull , warm , pleasant , unpleasant , and the like . concepts that are borrowed from music can describe some of these characteristics and provide explanations for phenomena observed in the autocorrelation of the speech signal . we have found that calculation of the fundamental frequency using the autocorrelation of the speech signal usually reveals several candidates for pitch , they are usually harmonies , multiplications of the fundamental frequency by natural numbers , as can be seen in fig7 and 8 . in expressive speech , there are also other maximum values , which are considered for the calculation of the fundamental frequency , but are usually ignored if they do not contribute to it . interestingly , in many cases they reveal a behaviour that can be associated with harmonic intervals , pure tones with relatively small ratio between them and the fundamental frequency , especially 3 : 2 , as can be seen in fig7 ( the line indicated by b ). other intervals , such as 4 : 3 and more complicated patterns also appear , as can be seen for example in fig8 . these candidates do not exist in all speech signals , and can appear only in parts of an utterance . it seems as if these relations might be associated with the musical notations of consonance . in other cases , the fundamental frequency is not very ‘ clean ’, and the autocorrelation reveals candidates with frequencies which are very close to the fundamental frequency . in music , such tones are associated with roughness or dissonance . there are other ratios that are considered unpleasant . the main high - value peaks of the autocorrelation correspond to frequencies that are both lower and higher than the fundamental frequency , with natural ratios , such as 1 : 2 , 1 : 3 and their multiples . in this work , these ratios are referred to as sub - harmonies , for the lower frequencies , and harmonies for the higher frequencies , intervals that are not natural numbers , such as 3 : 2 and 4 : 3 are referred to as harmonic intervals . sub - harmonies can suggest how many precise repetitions of f 0 exist in the frame , which can also suggest how pure its tone is . ( the measurement method limits the maximum value of detected sub - harmonies for low values of the fundamental frequency ). i suggest that this phenomenon appears in the speech signals and may be related to the harmonic properties , although the terminology which is used in musicology may be different . one of the first applications of physical science to the study of music perception was pythagoras &# 39 ; discovery that simultaneous vibrations of two string segments sound harmonious when their lengths form small integer ratios ( e . g . 1 : 2 , 2 : 3 , 3 : 4 ). these ratios create consonance , blends that sound pleasant . galileo postulated that tonal dissonance , or unpleasant , arises from temporal irregularities in eardrum vibrations that give rise to “ ever - discordant impulses ”. statistical analysis of the spectrum of human speech sounds show that the same ratios of the fundamental frequency are apparent in different languages . the neurobiology of harmony perception shows that information about the roughness and pitch of musical intervals is present in the temporal discharge patterns of the type i auditory nerve fibres , which transmit information about sound from the inner ear to the brain . these findings indicate that people are built to both perceive and generate these harmonic relations . the ideal harmonic intervals , their correlate in the 12 tones system of western music and their definitions as dissonances or consonances are listed in table 1 . the table also shows the differences between the values of these two sets of definition . these differences are smaller than 1 %. the different scales may be approximations . when two tones interact with each other and the interval or ratio between their frequencies create a repetitive pattern of amplitudes , their autocorrelation will reveal the repetitiveness of this pattern . for example , minor second ( 16 : 15 ) and tritone ( 7 : 5 = 1 . 4 , 45 : 32 = 1 . 40625 or 1 . 414 , the definition depends on the system in use ) are dissonances while perfect fifth ( 3 : 2 ) and forth ( 4 : 3 ) are consonances . minor second is an example of two tones of frequencies that are very close to each other , and can be associated with roughness , perfect fourth and fifth create nicely distinguishable repetitive patterns , which are associated with consonances . tritone , which is considered a dissonant , does not create such a repetitive pattern , while creating roughness ( signals of too close frequencies ) with the third and fourth harmonies ( multiplications ) of the pitch . consonance could be considered as the absence of dissonance or roughness . dissonance as a function of the ratios between two pure tones can be seen in fig9 . the curve of the dissonance perception has a minimum at unison , rises fast to maximum and decays again . it rises faster as the lower frequency in the ratio is higher . however , there seem to be well - known and robust results regarding the perceived sense of intervals when two pure tones of different frequencies interact with each other . two tones are perceived as pleasant when the ear can separate them clearly and when they are in unison , for all harmonies . relatively small intervals ( relative to the fundamental frequency ), are not well - distinguished and perceived as ‘ roughness ’. the autocorrelation of expressive speech signals reveals the same behaviour , therefore i included the ratios as appeared in the autocorrelation to the extracted features , and added measures that tested their relations to the documented harmonic intervals . the harmonies and the sub - harmonies were extracted from the autocorrelation maximum values . the calculation of the autocorrelation follows the sections of the fundamental frequency extraction algorithm ( algorithm 4 , or preferably algorithm 5 ), that describes the calculation of candidates . the rest of the calculation , which is described in algorithm 6 is performed after the calculation of the fundamental frequency is completed : if candidate & gt ; f 0 then it is considered as harmony , with ratio : else , if candidate & lt ; f 0 then it is considered as sub - harmony , with ratio : for each frame all the candidates and their weights , candidatew eights , are kept . the next stage is to check if the candidates are close to the known ratios of dissonances and consonances ( table 1 ), having established the fact that these ratios are significant . i examined for each autocorrelation candidate the nearest harmonic interval and the distance from this ideal value . for each ideal value i then calculated the normalised number of occurrences in the utterance , i . e . divided by the number of voiced frames in the utterance . the ideal values for sub - harmonies are the natural numbers . unfortunately , the number of sub - harmonies for low values of the fundamental frequencies is limited , but since the results are normalised for each speakers this effect is neutralised . these features can potentially explain how people can distinguish between real and acted expressions , including the distinction between real and artificial laughter , including behaviour that is subject to cultural display rules or stress . the distance of the calculated values from the ideal ratios may reveal the difference between natural and artificial expressions . the artificial sense may be derived from inaccurate transitions while speakers try to imitate the characteristics of their natural response . i have determined that the harmonic related features are among the most significant features for distinguishing between different types of expressions . time variations within utterances serve various communication roles . linguists and especially those who investigate pragmatic linguistics use sub - units of the utterance for observations . speech signals ( the digital representation of the captured / recorded speech ) can be divided roughly into several categories . the first is speech and silence , in which there are no speech or voice . the difference between them can be roughly defined by the energy level of the speech signal . the second category is voiced , where the fundamental frequency is not zero , i . e . there are vibrations of the vocal folds during speech , usually during the utterance of vowels , and unvoiced , where the fundamental frequency is zero , which happens mainly during silence and during the utterance of consonants such as / s /,/ t / and / p /, i . e . there are no vibrations of the vocal folds during articulation . the linguistic unit that is associated with these descriptions is the syllable , in which the main feature is the voiced part , which can be surrounded on one or both sides by unvoiced parts . the pitch , or fundamental frequency , defines the stressed syllable in a word , and the significant words in a sentence , in addition to the expressive non - textual content . this behaviour changes among languages and accents . in the context of non - verbal expressiveness , the distinction among these units allows the system to define characteristics of the different speech parts , and their time - related behaviour . it also facilitates following temporal changes among utterances , especially in the case of identical text . the features that are of interest are somewhat different from those in the purely linguistic analysis , such features may include , for example the amount of energy in the stressed part compared to the energy in the other parts , or the length of the unvoiced parts . two approaches to parsing were tried . in the first i tried to extract these units using image processing techniques from spectrograms of the speech signals and from smoothed spectrograms . spectrograms present the magnitude of the short time fourier transform ( stft ) of the signal , calculated on ( overlapping ) short time - frames . for the parsing i used two dimensional ( 2d ) edge detection techniques including zero crossing . however , most of the utterances were too noisy , and the speech itself has too many fluctuations and gradual changes so that the spectrograms are not smooth enough and do not give good enough results . 2 . locate peaks ( location and value ) of energy maximum value in the smoothed energy curve ( calculated with window ), that are at least 40 msec apart . 3 . delete very small energy peaks that are smaller than the silence threshold . 4 . beginning of sentence is the first occurrence of either the beginning of the first voiced part ( pitch ), or the point prior to an energy peak , in which the energy climbs above the silence threshold . 5 . end of sentence is the last occurrence of either pitch or of the energy getting below the silence threshold . 6 . remove insignificant minimum values of energy between two adjacent maximum values ( very short — duration valleys without a significant change in the energy . in a ‘ saddle ’ remove the local minimum and the smaller peak .) 7 . find pauses — look between two maximum peaks and find if the minimum is less than 10 percent of the maximum energy . if it is true then bracket it by the 10 percent limit . do not do it if the pause length is less than 30 msec or if there is a pitch in that frame . the second approach was to develop a rule based parsing . from analysis of the extracted features of many utterances from the two datasets in the time domain , rules for parsing were defined . these rules follow roughly the textual units . several parameters were considered for their definition , including the smoothed energy ( with window ), pitch contour , number of zero - crossings , and other edge detection techniques . algorithm 7 ( above ) describes the rules that define the beginning and end of a sentence , finds silence areas and significant energy maximum values and locations . the calculation of secondary time - related metrics is then done on voiced part , where there are both pitch and energy , places in which there is energy ( significant energy peaks ) with no pitch , and on durations of silence or pauses . the vocal features extracted from the speech signal reduce the amount of data because they are defined on ( overlapping ) frames , thus creating an array for each of the calculated features . however , these arrays are still very long and cannot be easily represented or interpreted . two types of secondary metrics have been extracted from each of the vocal features . they can be divided roughly into statistical metrics which are calculated for the whole utterance , such as maximum , mean , standard deviation , median and range , and to time - related metrics , which are calculated according to different duration properties of the vocal features and according to the parsing , and their statistical properties on occasions . it can be hard to find a precise manner to describe these relations mathematically as done in western music , and therefore it is preferable to use the extreme values of pitch at the locations of extreme values of the signal &# 39 ; s energy , the relations between the values , durations and the distances ( in time ) between consecutive extreme values . i have examined mainly two sets of features and definitions . the first set , listed in table 2 ( below ) was used for initial observations , and it was improved and extended to the a final version listed in table 3 ( below ). the final set includes the following secondary metrics of pitch : voiced length — the duration of instances in which the pitch is not zero , and unvoiced length , in which there is no pitch . statistical properties of its frequency were considered in addition to up and down slopes of the pitch , i . e . the first derivative or the differences in pitch value between adjacent time frames . finally , analysis of local extremum ( maximum ) peaks was added , including the frequency at the peaks , the differences in frequency between adjacent peaks ( maximum - maximum and maximum - minimum ), the distances between them in time and speech rate . similar examination was done for the energy ( smoothed energy with window ), including the value , the local maximum values , and the distances in time and value between adjacent local extreme values . another aspect of the energy was to evaluate the shape of the energy peak , or how the energy changes in time . the calculation was to find the relations of the energy peaks to rectangles which are defined by the peak maximum value and its duration or length . this metric gives a rough estimate for the nature of changes in time and the amount of energy invested . temporal characteristics were estimated also in terms of ‘ tempo ’, or more precisely in this case , with different aspects of speech rate . assuming , based on observations and music related literature that the tempo is set according to a basic duration unit whose products are repeated throughout an utterance , and this rate changes between expressions and different speech parts of the utterance . the assumption is that different patterns and combinations of these relative durations play a role in the expression . the initial stage was to gather the general statistics and check if it is enough for inference , which proved to be the case . further analysis should be done for accurate synthesis . the ‘ tempo ’ related metrics used here include the shortest part with pitch , that is the shortest segment around an energy peak that includes also pitch , the relative durations of silence to the shortest part , the relative duration of energy and no pitch and the relative durations of voiced parts . the harmonic related features include a measure of ‘ harmonicity ’, which in some preferred embodiments is measured by the sum of harmonic intervals in the utterance , the number of frames in which each of the harmonic intervals appeared ( as in table 1 ), the number of appearances of the intervals that are associated with consonance and those that are associated with dissonance and the sub - harmonies . the last group includes the filter bank and statistic properties of the energy in each frequency band . the centres of the bands are at 101 , 204 , 309 , 417 , 531 , 651 , 781 , 922 , 1079 , 1255 , 1456 , 1691 , 1968 , 2302 , 2711 , 3212 , 3822 , 4554 , 5412 , 6414 and 7617 hz . although the sampling rate in both databases allowed for frequency range that reaches beyond 10 khz , the recording equipment not necessarily does , therefore no further bands were employed . no doubt many other effective alternatives will occur to the skilled person . it will be understood that the invention is not limited to the described embodiments and encompasses modifications apparent to those skilled in the art lying within the spirit and scope of the claims appended hereto .	6
referring to fig1 , a cryptographic system is shown generally by the numeral 10 . a pair of correspondents 12 , 14 , referred to as alice and bob , communicate over a network 16 . each correspondent has an arithmetic logic unit ( alu ) 18 , 20 . the alu can be a general - purpose computer , with a cryptographic unit , which implements cryptographic protocols from instructions provided by software . the software may be provided on a data carrier or in memory . each correspondent has a long - term private key a , b and a corresponding long - term public key y a , y b . each correspondent has access to an authentic copy of the other correspondent &# 39 ; s long - term public key . it is desired to share a key between the correspondents using the mqv protocol . it is recognized that the mqv equations can be reorganized to provide efficient computations without necessarily using the truncation operation . the reorganization proceeds as follows . the formula k =( r b ( y b ) r b ) s a that is used to determine the key can be rearranged as k =( r b ( y b ) r b ) s a = r b s a y b s a r b , using the notation above . this rearrangement allows the key to be computed by using a technique known as simultaneous multiple exponentiation , which uses only one set of squares . to compute the multiple r b s a y b s a r b , two tables of small exponents of r b and y b respectively of a predetermined width are first established . the scalars s a and s a r b are then examined using windows of the predetermined width . the multiples of r b and y b corresponding to each window are retrieved from each respective table . the product of the table entries from the two windows is multiplied into an accumulator . the accumulator is then squared in accordance with the width of the window , and then the next window is examined . this process is repeated until each window has been examined , and therefore terminates with the accumulator holding the value of k . referring to fig2 , a method of computing a shared secret key is shown generally by the numeral 100 . alice selects an ephemeral private key x at random from the interval 1 to q − 1 ( 102 ). alice computes the corresponding ephemeral public key g x and sends it to bob ( 104 ). similarly , bob selects an ephemeral private key y at random from the interval 1 to q − 1 ( 106 ). bob computes the corresponding ephemeral public key g y and sends it to alice ( 108 ). alice computes s a =( x + ar a ) mod q and the shared secret k = r b s a y b s a r b ( 110 ) using simultaneous multiple exponentiation , as described below . bob computes s b =( y + br b ) mod q and the shared secret k = r b s a y b s a r b ( 112 ) using simultaneous multiple exponentiation . referring fig3 , a method of computing a simultaneous multiple exponentiation is shown generally by the numeral 300 . a window width of a predetermined number of bits w is first established ( 302 ). then , a table of small exponents α of r b is established ( 304 ) and a table of small exponents β of y b is established ( 306 ). the table entries consist of a column of possible bit combinations ( e . g . α = 1001 2 ), and a column of corresponding exponentiations ( e . g . r b 1001 2 ). then , the scalars s a and s a r b are examined using windows of the window width w ( 308 ). the powers of r b and y b corresponding to each window are retrieved from each respective table ( 310 ). the product of the table entries from the two windows is multiplied into an accumulator ( 312 ). the accumulator is then squared w times in accordance with the width w of the window ( 314 ), and then the next window is examined ( 316 ). the scalars are repeatedly examined and table entries multiplied into the accumulator and the accumulator squared w times for each repetition as described above ( 318 ) until the shared secret k is computed ( 320 ). it will be noted that in this embodiment one simultaneous multiple exponentiation is used instead of two separate exponentiations . accordingly , the number of squaring operations required corresponds to the number required for one exponentiation instead of that required for two separate exponentiations . it will be recognized that using the method of this embodiment , truncating the first exponent in an attempt to save squarings is not effective , since these squaring can be shared with the second multiplication . the truncation then saves only multiplications , not squarings , when applied to this embodiment since this embodiment uses simultaneous multiple exponentiation . referring to fig4 , an alternate embodiment is shown generally by the numeral 200 . in this embodiment , alice uses the improved method of computing the shared key , while bob can compute the shared key by any method . alice selects ( 202 ) x at random from the interval 1 to q − 1 . then , alice computes ( 204 ) g x and makes it available to bob ( 206 ). alice then obtains ( 208 ) g y from bob . alice computes ( 210 ) s a =( x + ar a ) mod q and then computes ( 212 ) the shared secret k = r b s a y b s a r b using simultaneous multiple exponentiation . referring to fig5 , an alternate embodiment is shown generally by the numeral 500 . in this embodiment , the correspondents of fig2 are shown carrying out the method in parallel . alice selects an ephemeral private key x at random from the interval 1 to q − 1 ( 502 ). bob selects an ephemeral private key y at random from the interval 1 to q − 1 ( 106 ). alice computes the ephemeral public key g x corresponding to the ephemeral private key x ( 504 ). similarly , bob computes his ephemeral public key g y ( 514 ). alice sends g x to bob and bob sends gy to alice . after alice receives bob &# 39 ; s ephemeral public key , she computes s a =( x + ar a ) mod q ( 506 ). then alice computes the shared secret k as before ( 508 ). after bob receives alice &# 39 ; s ephemeral public key , he computes s b as before ( 516 ). then bob computes k as before ( 518 ). thus , it will be understood that the order of the computations is not critical and it is only necessary that a correspondent have both its own private key and the other correspondent &# 39 ; s , ephemeral public key before computing s and k . referring to fig6 , an alternate method of computing a simultaneous multiple exponentiation is shown generally by the numeral 600 . the exponent s a is shown stored in a register 602 . the exponent s a r b is shown stored in a register 604 . each register has an associated pointer 603 , 605 . the pointers are aligned to designate corresponding bits in each exponent . a pair of switches 606 , 608 are provided . two multipliers 610 , 612 are shown , although their functionality could be performed by one multiplier . an accumulator 614 , a squaring operation 616 , and a control 618 are provided . in use , the pointer 603 is an input to the switch 606 which controls multiplier 610 so that when the corresponding bit of s a is set , the quantity r b is multiplied into the accumulator 514 . similarly , the pointer 605 is an input to the switch 608 which operates the multiplier 612 . the quantity y b is multiplied into the accumulator 614 when the corresponding bit of register 604 is set . after considering each exponent , the accumulator is squared 616 , and the control 618 operates to set the pointers 603 , 605 to the next bits of registers 602 , 604 . the process repeats until all the bits have been considered . in this way , the bits of the two exponents are considered simultaneously , and only one set of squares is performed . the above methods can be implemented in any group where the discrete logarithm problem is believed to be intractable . one example of such a group is an elliptic curve group , where the method is very similar however , the additive notation is usually used instead of multiplicative notation . in the elliptic curve setting , group multiplication corresponds to addition of elliptic curve points , and group exponentiation corresponds to scalar multiplication . in this case , the tables will contain a column possible bit combinations of the scalar ( e . g . 1001 2 ), and a column of corresponding point multiplications ( e . g . 1001 2 p ). referring therefore to fig7 , the method of fig5 is shown in an elliptic curve setting by the numeral 700 . the correspondents have common elliptic curve parameters comprising an elliptic curve , a finite field , a base point p of order q , and a function π to convert elliptic curve points to integers , each correspondent has a long term private key a , b and a corresponding long term public key y a = ap , y b = bp . alice selects an ephemeral private key x at random from the interval 1 to q − 1 ( 702 ). bob selects an ephemeral private key y at random from the interval 1 to q − 1 ( 712 ). alice computes the ephemeral public key xp corresponding to the ephemeral private key x ( 704 ). similarly , bob computes his ephemeral public key yp ( 714 ). alice sends xp to bob and bob sends yp to alice . after alice receives bob &# 39 ; s ephemeral public key , she computes s a =( x + aπ ( r a )) mod q ( 706 ). then alice computes the shared secret k = s a r b + s a π ( r b ) y b ( 708 ) using simultaneous multiple scalar multiplication ( fig8 ). after bob receives alice &# 39 ; s ephemeral public key , he computes s b =( y + bπ ( r b )) mod q ( 716 ). then bob computes k = s b r a + s b π ( r a ) y a ( 718 ) using simultaneous multiple scalar multiplication ( fig8 ). referring to fig8 , a method of performing simultaneous multiple scalar multiplication used in this embodiment is shown generally by the numeral 800 . a window width of a predetermined number of bits w is first established ( 802 ). then , a table of small exponents a of r b is established ( 804 ) and a table of small exponents β of y b is established ( 806 ). the table entries consist of a column of possible bit combinations ( e . g . α = 1001 2 ), and a column of corresponding scalar multiples ( e . g . 1001 2 r b ). then , the scalars s a and s a π ( r b ) are examined using windows of the window width w ( 808 ). the scalar multiples of r b and y b corresponding to each window are retrieved from each respective table ( 810 ). the sum of the table entries from the two windows is added into an accumulator ( 812 ). the accumulator is then doubled w times in accordance with the width w of the window ( 814 ), and then the next window is examined ( 816 ). the scalars are repeatedly examined and table entries added into the accumulator and the accumulator doubled w times for each repetition as described above ( 818 ) until the shared secret k is computed ( 820 ). although the invention has been described with reference to certain specific embodiments , various modifications thereof will be apparent to those skilled in the art without departing from the spirit and scope of the invention as outlined in the claims appended hereto .	7
hereinafter , the first embodiment of the present invention will be described with reference to fig1 a through 1g and fig2 a and 2b . fig1 a through 1g are cross - sectional views illustrating the flow of a process for fabricating a semiconductor device in this embodiment . first , as shown in fig1 a , an insulating film 102 ( thickness : 0 . 8 μm ), a first metal layer 103 formed by alternately stacking aluminum and a titanium alloy ( thickness : 0 . 5 μm ) and a first interlevel dielectric film 104 ( thickness : 1 . 0 μm ) are deposited in this order on a semiconductor substrate 101 on which a semiconductor active element ( not shown ) has been formed beforehand . thereafter , an interconnecting resist pattern 105 is formed thereon and an interlevel contact hole 106 is opened by dry etching . next , as shown in fig1 b , the interconnecting resist pattern 105 is removed , and an adhesion layer 107 made of tin / ti , for example , is deposited over the entire surface of the substrate as well as over the inside of the interlevel contact hole 106 . then , an interconnecting material 108 such as tungsten is further deposited thereon by a blanket w - cvd technique . and the adhesion layer 107 and the interconnecting material 108 are removed by a dry etching or cmp technique except for the respective portions existing inside the interlevel contact hole 106 . the respective portions of the adhesion layer 107 and the interconnecting material 108 , existing only in the interlevel contact hole 106 , constitute an interconnecting metal 109 altogether . then , as shown in fig1 c , a first - interconnect resist pattern 110 is formed over the first interlevel dielectric film 104 and the interconnecting metal 109 . assume the first - interconnect resist pattern 110 has been formed with an alignment error 111 . if the diameter of the interlevel contact hole 106 is 0 . 3 μm and the line width of a recess in the first - interconnect resist pattern 110 is also 0 . 3 μm , then the maximum permissible alignment error 111 between the interconnecting metal 109 filled in the interlevel contact hole 106 and the first - interconnect resist pattern 110 is 0 . 1 μm . [ 0034 ] fig2 a is a plan view illustrating how the positional relationship between the first - interconnect resist pattern 110 and the interconnecting metal 109 changes with the mask - to - mask placement error . in the lower part under the wave line in fig2 a , the position of the first - interconnect resist pattern 110 is misaligned with that of the interconnecting metal 109 . on the other hand , in the upper part over the wave line in fig2 a , the position of the first - interconnect resist pattern 110 matches with that of the interconnecting metal 109 . next , as shown in fig1 d , the layers on the surface of the substrate , which are exposed through the first - interconnect resist pattern 110 , are sequentially dry - etched by using a cf - based etching gas used for removing an oxide film and a cl - based etching gas used for removing aluminum . first , parts of the first interlevel dielectric film 104 , exposed through the openings of the first - interconnect resist pattern 110 , are removed by dry etching using the cf - based etching gas at a low temperature . in this case , part of the interconnecting metal 109 corresponding to a misaligned portion 112 is not etched by the cf - based etching gas . then , parts of the first metal layer 103 , exposed through the openings of the first - interconnect resist pattern 110 , are removed by dry etching using the cl - based etching gas until the insulating film 102 is exposed . the part of the interconnecting metal 109 corresponding to the misaligned portion 112 is not etched by the cl - based etching gas , either . [ 0036 ] fig2 b is a perspective view illustrating how the positional relationship between lines in the first interconnect layer 113 and the interconnecting metal 109 changes with the mask - to - mask placement error . first , as to a line 113 b that has been formed out of the first metal layer 103 by dry etching without having been misaligned , the interconnecting metal 109 having a diameter equal to the width of the line 113 b is formed on the upper surface of the line 113 b . on the other hand , as to a line 113 c that has been formed out of the first metal layer 103 by dry etching with an alignment error , part of the first metal layer 103 located under the interconnecting metal 109 is not etched during the dry etching . accordingly , the part of the first metal layer 103 located under the interconnecting metal 109 is not etched but left in a self - aligned manner in the misaligned portion 112 shown in fig1 d . as a result , a line 113 c is shaped as shown in fig2 b . therefore , the line 113 b or 113 c ( both identified by 113 a in fig1 d ) of the first interconnect layer 113 is formed without fail under the entire bottom of the interconnecting metal 109 . also , since the portions under the first - interconnect resist pattern 110 are not etched , the first interlevel dielectric film 104 remains as it is in the portions over the lines 113 a in the first interconnect layer 113 where the interconnecting metal 109 does not exist . that is to say , either the first interlevel dielectric film 104 or the interconnecting metal 109 always exists over the lines 113 a in the first interconnect layer 113 . accordingly , portions of the first metal layer 103 existing under the interconnecting metal 109 and the first interlevel dielectric film 104 constitute the lines 113 a in the first interconnect layer 113 . the total thickness of the lines 113 a in the first interconnect layer 113 , formed out of the first metal layer 103 , and the first interlevel dielectric film 104 is 1 . 5 μm . thus , the aspect ratio of a recess 115 formed in a line - to - line space 114 , which is a region between adjacent lines in the first interconnect layer 113 and has the minimum width of 0 . 3 μm , is about five . it is noted that a dummy interconnect pattern may be formed in a field portion 116 where the lines of the first interconnect layer 113 do not exist . next , as shown in fig1 e , the first - interconnect resist pattern 110 is removed . then , a second interlevel dielectric film 117 is deposited over the insulating film 102 , the first interlevel dielectric film 104 and the interconnecting metal 109 on the semiconductor substrate 101 by using a plasma cvd apparatus . part or all of a recess formed in a line - to - line space 114 is not filled in with the second interlevel dielectric film 117 , but forms an air gap 118 . in a recess having a high aspect ratio , in particular , the entire region of a line - to - line space 114 is turned into an air gap 118 . subsequently , as shown in fig1 f , the surface of the second interlevel dielectric film 117 is planarized by a cmp technique such that the respective surfaces of the first interlevel dielectric film 104 , the interconnecting metal 109 and the second interlevel dielectric film 117 form a single plane . in this embodiment , the first and second interlevel dielectric films 104 and 117 are made of different materials and the etching rate of the first interlevel dielectric film 104 is set smaller than that of the second interlevel dielectric film 117 during the cmp process . in this manner , the first interlevel dielectric film 104 is used as an etching stopper . even in a recess having a high aspect ratio , the upper part thereof is filled in with the second interlevel dielectric film 117 to a certain degree . accordingly , no opening is formed over any air gap 118 through the surface of the second interlevel dielectric film 117 after cmp is finished . then , as shown in fig1 g , a metal layer formed by alternately stacking aluminum and a titanium alloy is deposited thereon and subjected to photolithography and dry etching , thereby forming a second interconnect layer 119 . as described above , in this embodiment , part or all of a line - to - line space 114 is turned into an air gap 118 . accordingly , the relative dielectric constant between adjacent lines 113 a in the first interconnect layer 113 can be reduced at the line - to - line space 114 . in particular , when a recess 115 formed in a line - to - line space 114 has a high aspect ratio , the entire region of the line - to - line space 114 is turned into an air gap 118 . as a result , the relative dielectric constant between adjacent lines 113 a in the first interconnect layer 113 can be minimized . in addition , since the first interconnect layer 113 is formed after the interconnecting metal 109 has been formed , the first interconnect layer 113 exists without fail under the entire bottom of the interconnecting metal 109 . accordingly , it is possible to prevent a contact failure from being caused between the first interconnect layer 113 and the interconnecting metal 109 . moreover , after the interconnecting metal 109 has been filled in the interlevel contact hole 106 provided in the first interlevel dielectric film 104 , the first interconnect layer 113 and the second interlevel dielectric film 117 are formed in this order . accordingly , even if a mask - to - mask placement error has been caused during the formation of the first interconnect layer 113 , either the interconnecting metal 109 or the first interlevel dielectric film 104 always exists on the upper surface of the first interconnect layer 113 . and the interconnecting metal 109 is never filled in any air gap 118 formed simultaneously with the second interlevel dielectric film 117 . accordingly , it is possible to prevent a shortcircuit failure from being caused between adjacent lines 113 a in the first interconnect layer 113 or between a line 113 a and the semiconductor substrate 101 through the interconnecting metal 109 . hereinafter , the second embodiment of the present invention will be described with reference to fig3 a through 3c illustrating the flow of a process for fabricating a semiconductor device in this embodiment . the same process steps as those illustrated in fig1 a through 1d are also performed prior to the process step shown in fig3 a . thus , the same components as those used in the first embodiment will be identified by the same reference numerals and the description thereof will be omitted herein . unlike the first embodiment in which the second interlevel dielectric film 117 is deposited by using a plasma cvd apparatus , a second interlevel dielectric film 217 is formed in this embodiment by using an applicator . the second interlevel dielectric film 217 may be an organic film made of organic poly - siloxane or an organic material containing fluorine , or an inorganic porous film , for example . many of these materials have fluidity . first , as shown in fig3 a , the material is applied onto the first interlevel dielectric film 104 , the interconnecting metal 109 and the line - to - line spaces 214 . in this manner , the recesses in the line - to - line spaces 214 are filled in with the fluid material , thereby forming the second interlevel dielectric film 217 without any air gap . as the material of the second interlevel dielectric film 217 , a material having a lower relative dielectric constant than that of the first interlevel dielectric film 104 is selected . accordingly , the relative dielectric constant between adjacent lines 113 a in the first interconnect layer 113 can be reduced at the line - to - line spaces 214 . subsequently , as shown in fig3 b , the surface of the second interlevel dielectric film 217 is planarized by a cmp technique such that the respective surfaces of the first interlevel dielectric film 104 , the interconnecting metal 109 and the second interlevel dielectric film 217 form a single plane . in this embodiment , the first and second interlevel dielectric films 104 and 217 are made of different materials and the etching rate of the first interlevel dielectric film 104 is set smaller than that of the second interlevel dielectric film 217 during the cmp process . in this manner , the first interlevel dielectric film 104 is used as an etching stopper . then , as shown in fig3 c , a metal layer formed by alternately stacking aluminum and a titanium alloy is deposited thereon and subjected to photolithography and dry etching , thereby forming a second interconnect layer 219 . as described above , in this embodiment , the line - to - line spaces 214 are entirely filled in with the second interlevel dielectric film 217 made of a material having a lower relative dielectric constant than that of the first interlevel dielectric film 104 . thus , the relative dielectric constant between adjacent lines 113 a in the first interconnect layer 113 can be reduced at the line - to - line spaces 214 . in addition , the relative dielectric constant can be determined based on the material of the second interlevel dielectric film 217 . in addition , since the first interconnect layer 113 is formed after the interconnecting metal 109 has been formed , the first interconnect layer 113 always exists under the entire bottom of the interconnecting metal 109 . accordingly , it is possible to prevent a contact failure from being caused between the first interconnect layer 113 and the interconnecting metal 109 . moreover , after the interconnecting metal 109 has been filled in the interlevel contact hole 106 provided in the first interlevel dielectric film 104 , the first interconnect layer 113 and the second interlevel dielectric film 217 are formed in this order . accordingly , even if a mask - to - mask placement error has been caused during the formation of the first interconnect layer 113 , either the interconnecting metal 109 or the first interlevel dielectric film 104 always exists on the upper surface of the first interconnect layer 113 . and the second interlevel dielectric film 217 always exists in the line - to - line spaces 214 . accordingly , it is possible to prevent a shortcircuit failure from being caused between adjacent lines 113 a in the first interconnect layer 113 or between a line 113 a and the semiconductor substrate 101 through the interconnecting metal 109 . hereinafter , the third embodiment of the present invention will be described with reference to fig4 a through 4d and fig5 . fig4 a through 4d are cross - sectional views illustrating the flow of a process for fabricating a semiconductor device in this embodiment . the same process steps as those illustrated in fig1 a through 1f are also performed prior to the process step shown in fig4 a , except that the thickness of a first interlevel dielectric film 304 is set larger ( e . g ., at 2 . 5 μm ). thus , the same components as those used in the first embodiment will be identified by the same reference numerals and the description thereof will be omitted herein . first , as shown in fig4 a , a second - interconnect inverted resist pattern 320 is formed by photolithography over the first interlevel dielectric film 304 , an interconnecting metal 309 and a second interlevel dielectric film 317 . assume the second - interconnect inverted resist pattern 320 has been formed with an alignment error 311 . if the diameter of the interlevel contact hole is 0 . 3 μm and the line width of a recess in the second - interconnect inverted resist pattern 320 is also 0 . 3 μm , then the maximum permissible alignment error 311 between the interconnecting metal 309 filled in the interlevel contact hole and the second - interconnect inverted resist pattern 320 is 0 . 1 μm . next , as shown in fig4 b , the first and second interlevel dielectric films 304 and 317 are etched , thereby forming interconnect recesses 321 a having a depth of 0 . 5 μm . then , as shown in fig4 c , an adhesion layer ( not shown ) made of a titanium alloy is deposited on the recesses and a second metal layer 322 made of aluminum , an aluminum / copper alloy or copper is formed by vacuum evaporation , cvd or the like . subsequently , as shown in fig4 d , the second metal layer 322 is removed by a cmp technique except for the portions existing in the interconnect recesses 321 a to form a second interconnect layer 323 . next , it will be described with reference to fig5 and fig4 b through 4d how the positional relationship between the second interconnect layer 323 and the interconnecting metal 309 changes owing to the misalignment of the second - interconnect inverted resist pattern 320 . fig5 is a perspective view illustrating how the positional relationship between the interconnect recesses 321 a , where the second interconnect layer 323 is to be formed , and the interconnecting metal 309 changes with the mask - to - mask placement error . first , as to an interconnect recess 321 b that has been formed by dry etching without having been misaligned , the interconnect recess 321 b has a width equal to the diameter of the interconnecting metal 309 . since a line of the second interconnect layer 323 is formed inside the interconnect recess 321 b , the interconnecting metal 309 and the line are in contact with each other over substantially the entire side face of the interconnecting metal 309 . on the other hand , as to an interconnect recess 321 c that has been formed by dry etching with an alignment error , the interconnect recess 321 c , having a width equal to the diameter of the interconnecting metal 309 , is formed with an alignment error 311 shown in fig4 b . since the interconnecting metal 309 is not etched , the side face of the interconnecting metal 309 is exposed in the interconnect recess 321 c except for the portion of the interconnecting metal 309 ingrown into the first interlevel dielectric film 304 by the alignment error 311 . accordingly , most of the side face of the interconnecting metal 309 comes into contact with the second metal layer 322 shown in fig4 c , and with the second interconnect layer 323 shown in fig4 d after cmp has been performed . as described above , in this embodiment , even if the second - interconnect inverted resist pattern 320 used for forming the second interconnect layer 323 has been misaligned , most of the side face of the interconnecting metal 309 is in contact with the second interconnect layer 323 . accordingly , in this embodiment , not only the same effects as those of the first embodiment can be attained , but the reliability in connecting the interconnecting metal 309 to the second interconnect layer 323 can also be improved , even if the second - interconnect inverted resist pattern 320 has been misaligned . hereinafter , a method for fabricating a semiconductor device in the fourth embodiment of the present invention will be described with reference to fig6 a through 6i . first , as shown in fig6 a , an insulating film 102 ( thickness : 0 . 8 μm ), a first metal layer 103 formed by alternately stacking aluminum and a titanium alloy ( thickness : 0 . 5 μm ) and a first interlevel dielectric film 104 ( thickness : 1 . 0 μm ) are deposited in this order on a semiconductor substrate 101 on which a semiconductor active element ( not shown ) has been formed beforehand . thereafter , an interconnecting resist pattern 105 is formed and an interlevel contact hole 106 is opened by dry etching . next , as shown in fig6 b , the interconnecting resist pattern 105 is removed , and an adhesion layer 107 made of tin / ti , for example , is deposited over the entire surface of the substrate as well as over the inside of the interlevel contact hole 106 . then , an interconnecting material 108 such as tungsten is further deposited thereon by a blanket w - cvd technique . and the adhesion layer 107 and the interconnecting material 108 are removed by a dry etching or cmp technique except for the respective portions existing inside the interlevel contact hole 106 . the portions of the adhesion layer 107 and the interconnecting material 108 , existing only in the interlevel contact hole 106 , constitute an interconnecting metal 109 altogether . subsequently , as shown in fig6 c , the first interlevel dielectric film 104 is etched by about 0 . 5 μm to adjust the thickness of the residual portion of the first interlevel dielectric film 104 at 0 . 5 μm . as a result , the interconnecting metal 109 protrudes upward from the surface of the first interlevel dielectric film 104 . then , as shown in fig6 d , a first - interconnect resist pattern 110 is formed over the first interlevel dielectric film 104 and the interconnecting metal 109 . assume the first - interconnect resist pattern 110 has been formed with an alignment error 111 . if the diameter of the interlevel contact hole 106 is 0 . 3 μm and the line width of a recess in the first - interconnect resist pattern 110 is also 0 . 3 μm , then the maximum permissible alignment error 111 between the interconnecting metal 109 , filled in the interlevel contact hole 106 , and the first - interconnect resist pattern 110 is 0 . 1 μm . [ 0057 ] fig2 a is a plan view illustrating how the positional relationship between the first - interconnect resist pattern 110 and the interconnecting metal 109 changes with the mask - to - mask placement error . in the lower part under the wave line in fig2 a , the position of the first - interconnect resist pattern 110 is misaligned with that of the interconnecting metal 109 . on the other hand , in the upper part over the wave line in fig2 a , the position of the first - interconnect resist pattern 110 matches with that of the interconnecting metal 109 . next , as shown in fig6 e , the layers on the surface of the substrate , which are exposed through the openings of the first - interconnect resist pattern 110 , are sequentially dry - etched by using a cf - based etching gas used for removing an oxide film and a cl - based etching gas used for removing aluminum . first , parts of the first interlevel dielectric film 104 , exposed through the openings of the first - interconnect resist pattern 110 , are removed by dry etching using the cf - based etching gas at a low temperature . in this case , part of the interconnecting metal 109 corresponding to a misaligned portion 112 is not etched by the cf - based etching gas . then , parts of the first metal layer 103 , exposed through the openings of the first - interconnect resist pattern 110 , are removed by dry etching using the cl - based etching gas until the insulating film 102 is exposed . in this manner , the first interconnect layer 113 is formed . the part of the interconnecting metal 109 corresponding to the misaligned portion 112 is not etched by the cl - based etching gas , either . [ 0059 ] fig2 b is a perspective view illustrating how the positional relationship between lines in the first interconnect layer 113 and the interconnecting metal 109 changes with the mask - to - mask placement error . first , as to a line 113 b that has been formed out of the first metal layer 103 by dry etching without having been misaligned , the interconnecting metal 109 having a diameter equal to the width of the line 113 b is formed on the upper surface of the line 113 b . on the other hand , as to a line 113 c that has been formed out of the first metal layer 103 by dry etching with an alignment error , part of the first metal layer 103 located under the interconnecting metal 109 is not etched during the dry etching . accordingly , the part of the first metal layer 103 located under the interconnecting metal 109 is not etched but left in a self - aligned manner in the misaligned portion 112 shown in fig6 e . as a result , a line 113 c is shaped as shown in fig2 b . therefore , the line 113 b or 113 c ( both identified by 113 a in fig6 e ) of the first interconnect layer 113 is formed without fail under the entire bottom of the interconnecting metal 109 . also , since the portions under the first - interconnect resist pattern 110 are not etched , the first interlevel dielectric film 104 remains as it is in the portions over the first interconnect layer 113 where the interconnecting metal 109 does not exist . that is to say , either the first interlevel dielectric film 104 or the interconnecting metal 109 always exists over the first interconnect layer 113 . next , as shown in fig6 f , the insulating film 102 is etched by about 0 . 5 μm in accordance with a dry etching technique using the cf - based etching gas . in this manner , the first interconnect layer 113 is formed to be sandwiched by upper and lower insulating films 102 and 104 . in fig6 f , the non - etched portions of the insulating film 102 immediately under the lines 113 a in the first interconnect layer 113 are identified by 112 a . accordingly , the first metal layer 103 , existing under the interconnecting metal 109 or the first interlevel dielectric film 104 , constitutes the first interconnect layer 113 . the total thickness of the first interconnect layer 113 , formed out of the first metal layer 103 , the first interlevel dielectric film 104 and the insulating film 112 a is 1 . 5 μm . thus , the aspect ratio of a recess 115 formed in a line - to - line space 114 , which is a region between adjacent lines 113 a in the first interconnect layer 113 and has the minimum width of 0 . 3 μm , is about five . it is noted that a dummy interconnect pattern may be formed in a field portion 116 where the first interconnect layer 113 does not exist . next , as shown in fig6 g , the first - interconnect resist pattern 110 is removed . then , a second interlevel dielectric film 117 is deposited over the insulating film 102 , the first interlevel dielectric film 104 and the interconnecting metal 109 on the semiconductor substrate 101 by using a plasma cvd apparatus . a recess 115 formed in a line - to - line space 114 is partially or entirely not filled in with the second interlevel dielectric film 117 , but turned into an air gap 118 . in a recess having a high aspect ratio , in particular , the entire region of the line - to - line space 114 is turned into an air gap 118 . subsequently , as shown in fig6 h , the surface of the second interlevel dielectric film 117 is planarized by a cmp technique such that the respective surfaces of the interconnecting metal 109 and the second interlevel dielectric film 117 form a single plane . even in a recess having a high aspect ratio , the upper part thereof is filled in with the second interlevel dielectric film 117 to a certain degree . accordingly , no opening is formed over any air gap 118 through the surface of the second interlevel dielectric film 117 after cmp is finished . then , as shown in fig6 i , a metal layer formed by alternately stacking aluminum and a titanium alloy is deposited thereon and subjected to photolithography and dry etching , thereby forming a second interconnect layer 119 . hereinafter , it will be described with reference to fig7 a and 7b and fig8 a and 8b how the shape of an air gap changes with the manner in which the second interlevel dielectric film 117 is deposited . first , fig7 a will be referred to . fig7 a illustrates an ideal state where the second interlevel dielectric film 117 has not ingrown into the recesses 115 at all and the recesses 115 are entirely occupied by air gaps . in this case , since no dielectric exists between adjacent lines 113 a , the line - to - line capacitance cl is very small . also , in fig7 a , the upper end of an air gap is not higher than the upper surface of the first interlevel dielectric film 104 . accordingly , even after the surface of the second interlevel dielectric film 117 has been polished by cmp , the air gaps are less likely to be exposed . if the air gaps communicate with the outside through the polished surface of the second interlevel dielectric film 117 subjected to the cmp process , then the function of the interlevel dielectric film 117 is lost and shortcircuit possibly happens between lines . [ 0065 ] fig7 b illustrates a state where the second interlevel dielectric film 117 has been deposited on the bottom and side faces of the recesses 115 and a small part of each recess 115 is occupied by an air gap . such a state is established if the second interlevel dielectric film 117 has been deposited with satisfactory step coverage . for example , in performing plasma cvd using teos as a source material , before the upper part of a recess 115 is completely filled in with the second interlevel dielectric film 117 being deposited , the interlevel dielectric film having a certain thickness is deposited on the bottom and side faces of the recess 115 . as a result , the capacitance c 2 between adjacent lines 113 a adversely increases . [ 0066 ] fig8 a illustrates a state where the second interlevel dielectric film 117 has not ingrown into the recesses 115 at all and the upper part 118 of an air gap reaches a higher level than the upper surface of the first interlevel dielectric film 104 . such a state is established if the second interlevel dielectric film 117 has been deposited with poor step coverage and high directivity . for example , if the second interlevel dielectric film 117 is a so - called “ high - density plasma ( hdp ) film ”, the air gaps such as those shown in fig8 a are obtained . in this case , since no dielectric is deposited inside the recesses 115 , the capacitance c 3 between adjacent lines 113 a is smaller . an hdp film is formed by using an hdp apparatus . if an hdp film is deposited in an hdp apparatus with a bias voltage applied to the substrate , an etching phenomenon also happens in competition with the deposition . as a result , the dielectric film is deposited on the bottom of the recesses and the upper end of an air gap does not exceed the upper surface of the first interlevel dielectric film 104 . the air gaps in such a shape are shown in fig8 b . if the hdp film , which has been deposited with a bias voltage applied to the substrate , is used as the second interlevel dielectric film , only a small amount of dielectric is deposited on the bottom of the recesses . however , if the insulating film , which is an underlying layer of the first interconnect layer , has been etched , the deposited dielectric is located at a lower level than that of the first interconnect layer . accordingly , the capacitance between the lines 113 a remains low . thus , if the process step of etching the insulating film 102 has been performed as shown in fig6 f , the capacitance c 4 between the lines 113 a is kept low , even though a small amount of dielectric has been deposited on the bottom of the recesses . this point will be further described with reference to fig9 a and 9b . fig9 a illustrates the shape of air gaps where the process step of etching the insulating film 102 has not been performed , while fig9 b illustrates the shape of air gaps where the process step of etching the insulating film 102 has been performed . in fig9 a , if a dielectric has been deposited on the bottom of the recesses , then the capacitance c 5 is larger than the capacitance c 4 because the dielectric exists between adjacent lines . accordingly , in forming the second interlevel dielectric film in accordance with a deposition method for forming the air gaps in such shapes as those shown in fig7 b and 8b , it is preferable to make the bottom of the recesses lower than the first interconnect layer 113 by performing the process step of etching the insulating film 102 . in order to reduce the line - to - line capacitance , the air gaps of such a shape as shown in fig8 b are most preferable . however , if such air gaps are formed , it is highly probable that the second interlevel dielectric film is planarized and etched by cmp to the level on which the upper end of the air gaps is located . nevertheless , if the interconnecting metal 109 is formed to protrude upward from the upper surface of the first interlevel dielectric film 104 , the chemical / mechanical polishing can be stopped at the level of the upper surface of the interconnecting metal 109 . that is to say , the interconnecting metal 109 can function as a kind of etching stopper layer . in such a case , it is easy to control the cmp process such that the polished and etched surface is located higher than the upper end of the air gaps . accordingly , even if the air gaps of the shape shown in fig8 a have been formed , problems are less likely to happen . also , if the air gaps of the shape shown in fig8 a are formed , the necessity of etching the insulating film 102 is relatively low . however , if the insulating film 102 has been etched , the line - to - line capacitance c 3 can be lower as compared with the case where the insulating film 102 has not been etched at all . the reason is as follows . the line - to - line capacitance is determined by the physical properties of a space of a certain dimension located between two adjacent lines . accordingly , since the line - to - line capacitance is also affected by the relative dielectric constants of spaces over and under the space adjoining the lines , the insulating film is preferably etched . considering these points , it can be understood that partially etching the insulating film 102 at the spaces between adjacent lines 113 a is advantageous in reducing the line - to - line capacitance for various shapes of air gaps . as described above , in this embodiment , part or all of a line - to - line space 114 is turned into an air gap 118 . accordingly , the relative dielectric constant between lines 113 a in the first interconnect layer 113 can be reduced at the line - to - line space 114 . in particular , when a recess 115 formed in a line - to - line space 114 has a high aspect ratio , the entire region of the line - to - line space 114 is turned into an air gap 118 . as a result , the relative dielectric constant between the lines 113 a can be minimized . in addition , since the first interconnect layer 113 is formed after the interconnecting metal 109 has been formed , the first interconnect layer 113 always exists under the entire bottom of the interconnecting metal 109 . accordingly , it is possible to prevent a contact failure from being caused between the first interconnect layer 113 and the interconnecting metal 109 . moreover , after the interconnecting metal 109 has been filled in the interlevel contact hole 106 provided in the first interlevel dielectric film 104 , the first interconnect layer 113 and the second interlevel dielectric film 117 are formed in this order . accordingly , even if a mask - to - mask placement error has been caused during the formation of the first interconnect layer 113 , either the interconnecting metal 109 or the first interlevel dielectric film 104 always exists on the upper surface of the first interconnect layer 113 . and the interconnecting metal 109 is never filled in any air gap 118 formed simultaneously with the second interlevel dielectric film 117 . accordingly , it is possible to prevent a shortcircuit failure from being caused between adjacent lines 113 a in the first interconnect layer 113 or between a line 113 a and the semiconductor substrate 101 through the interconnecting metal 109 . hereinafter , the fifth embodiment of the present invention will be described with reference to fig1 a through 10d illustrating the flow of a process for fabricating a semiconductor device in this embodiment . the same process steps as those illustrated in fig1 a through 1d and fig6 e and 6f are also performed prior to the process step shown in fig1 a . thus , the same components as those used in the first embodiment will be identified by the same reference numerals and the description thereof will be omitted herein . unlike the first embodiment in which the second interlevel dielectric film 117 is deposited by using a plasma cvd apparatus , a second interlevel dielectric film 212 is formed in this fifth embodiment by using an applicator . the second interlevel dielectric film 212 may be an organic film made of organic poly - siloxane or an organic material containing fluorine , or an inorganic porous film , for example . many of these materials have fluidity . first , as shown in fig1 a , the material is applied onto a first interlevel dielectric film 204 , an interconnecting metal 208 and the line - to - line spaces 215 formed on the semiconductor substrate 201 . in this manner , the recesses in the line - to - line spaces 215 are filled in with the fluid material , thereby forming the second interlevel dielectric film 212 without any air gap . as the material of the second interlevel dielectric film 212 , a material having a lower relative dielectric constant than that of the first interlevel dielectric film 204 is selected . accordingly , the relative dielectric constant between adjacent lines in the first interconnect layer 203 can be reduced at the line - to - line spaces 215 . subsequently , as shown in fig1 b , the surface of the second interlevel dielectric film 212 is planarized by a cmp technique such that the respective surfaces of the first interlevel dielectric film 204 , the interconnecting metal 208 and the second interlevel dielectric film 212 form a single plane . in this embodiment , the first and second interlevel dielectric films 204 and 212 are made of different materials and the etching rate of the first interlevel dielectric film 204 is set smaller than that of the second interlevel dielectric film 212 during the cmp process . in this manner , the first interlevel dielectric film 204 is used as an etching stopper . then , as shown in fig1 c , only the second interlevel dielectric film 212 is selectively etched in the depth direction by about 0 . 3 μm , and a third interlevel dielectric film 214 is deposited to be about 0 . 5 μm thick . and then the surface of the third interlevel dielectric film 214 is planarized again by a cmp technique such that the respective surfaces of the first interlevel dielectric film 204 , the interconnecting metal 208 and the third interlevel dielectric film 214 form a single plane . next , as shown in fig1 d , a metal layer formed by alternately stacking aluminum and a titanium alloy is deposited thereon and subjected to photolithography and dry etching , thereby forming a second interconnect layer 216 . as described above , in this embodiment , the line - to - line spaces 215 are entirely filled in with the second interlevel dielectric film 212 made of a material having a lower relative dielectric constant than that of the first interlevel dielectric film 204 . thus , the relative dielectric constant between adjacent lines in the first interconnect layer 203 can be reduced at the line - to - line spaces 215 . in addition , the relative dielectric constant can be determined based on the material of the second interlevel dielectric film 212 . in addition , since the first interconnect layer 203 is formed after the interconnecting metal 208 has been formed , the first interconnect layer 203 always exists under the entire bottom of the interconnecting metal 208 . accordingly , it is possible to prevent a contact failure from being caused between the first interconnect layer 203 and the interconnecting metal 208 . moreover , after the interconnecting metal 208 has been filled in the interlevel contact hole provided in the first interlevel dielectric film 204 , the first interconnect layer 203 and the second interlevel dielectric film 212 are formed in this order . accordingly , even if a mask - to - mask placement error has been caused during the formation of the first interconnect layer 203 , either the interconnecting metal 208 or the first interlevel dielectric film 204 always exists on the upper surface of the first interconnect layer 203 . and the second interlevel dielectric film 212 always exists in the line - to - line spaces 215 . accordingly , it is possible to prevent a shortcircuit failure from being caused between adjacent lines in the first interconnect layer 203 or between a line and the semiconductor substrate 201 through the interconnecting metal 208 . in this embodiment , parts of the insulating film 202 located in the line - to - line spaces between adjacent lines in the first interconnect layer 203 are also etched . accordingly , the line - to - line capacitance is substantially determined by the relative dielectric constant of the second interlevel dielectric film 212 . if the parts of the insulating film 202 located in the line - to - line spaces between adjacent lines in the first interconnect layer 203 are not etched , then the parts of the insulating film 202 located in the vicinity of the line - to - line spaces between adjacent lines in the first interconnect layer 203 increase the line - to - line capacitance to a certain degree . moreover , in this embodiment , the third interlevel dielectric film 214 is formed . accordingly , even if a material poorly resistant to etching or plasma is used for the second interlevel dielectric film 212 , the second interlevel dielectric film 212 is not damaged during the process step of forming the second interconnect layer 216 . thus , the third interlevel dielectric film 214 is preferably made of a material highly resistant to etching or plasma . even if the relative dielectric constant of the third interlevel dielectric film 214 increases because of the selection of such a material , the line - to - line capacitance of the first interconnect layer 203 is not increased . in the embodiment illustrated in fig1 a through 10d , no air gaps are formed in the line - to - line spaces 215 . alternatively , air gaps may be formed in the line - to - line spaces 215 . in the sixth embodiment , the same process steps as those of the fifth embodiment are performed before the second interlevel dielectric film is formed . the sixth embodiment is characterized by the process step of forming the second interlevel dielectric film . hereinafter , the process step of forming the second interlevel dielectric film will be described in detail with reference to fig1 a through 11c . [ 0085 ] fig1 a through 11c illustrate a region where a relatively narrow recess 115 a having a width of 0 . 5 μm or less and a relatively broad recess 115 b having a width larger than 0 . 5 μm ( e . g ., 0 . 8 μm or more ) have been formed . in particular , fig1 a and 11b show the cross sections , in each of which the second interlevel dielectric film 117 is made of a single type of film . in the example shown in fig1 a , an insulating film with relatively poor step coverage has been deposited . examples of such films with poor step coverage include a plasma - oxidized film formed in a parallel - plate plasma cvd apparatus by using silane / n 2 o - based gas plasma . if such a film is used , then air gaps are formed in both of the recesses 115 a and 115 b . in the relatively broad recess 115 b , a large air gap is formed . accordingly , the upper end of the air gap in the recess 115 b possibly exceeds the resulting level of the second interlevel dielectric film 117 at which cmp is to be stopped ( in this specification , such a level will be called a “ cmp target level ”). if such a large air gap has been formed , the air gap is possibly exposed through the polished surface after the cmp process is finished . in such a case , a disconnection or shortcircuit failure of the second interconnect layer may happen . on the other hand , in the example shown in fig1 b , a dielectric film , which can generally fill in a gap rather satisfactorily , has been deposited as the second interlevel dielectric film 117 . examples of such a film include a plasma - oxidized film formed by using high - density plasma ( hdp ). if such a film is used , then the second interlevel dielectric film 117 is deposited on the bottom and side faces of the relatively narrow recess 115 a . as a result , an air gap of the size smaller than that of the recess 115 a is formed in the recess 115 a . on the other hand , the relatively broad recess 115 b is filled in with the second interlevel dielectric film 117 and no air gap is observed therein . the hdp film is formed by using - an hdp apparatus . if the hdp film is deposited in the hdp apparatus with a bias voltage applied to the substrate , an etching phenomenon also happens in competition with deposition . as a result , the dielectric film is deposited on the bottom of the recess and the gap can be filled in with the film more satisfactorily . in this case , the upper end of an air gap does not reach the cmp target level . however , since a smaller air gap is formed in the recess 115 a , the line - to - line capacitance is not reduced so much . in the embodiment shown in fig1 c , in order to attain the advantages of these two types of films at the same time , the second interlevel dielectric film 117 is made up of dielectric layers formed by at least two different methods . specifically , first , the upper part of the relatively narrow recess 115 a is substantially covered with a first interlevel dielectric layer 117 a and then the other relatively broad recess 115 b is filled in with a second interlevel dielectric layer 117 b . in particular , the first interlevel dielectric layer 117 a is formed in a parallel - plate plasma cvd apparatus by using silane / n 2 o - based gas plasma and then the second interlevel dielectric layer 117 b is deposited in an hdp apparatus with a bias voltage applied to the substrate . the first and second interlevel dielectric layers 117 a and 117 b are made of silicon dioxide , for example . alternatively , the second interlevel dielectric layer 117 b may be an organic coating film ( made of polyarylether , for example ) having a low relative dielectric constant . the first interlevel dielectric layer 117 a may be formed using silane , oxygen and argon gases at a pressure of 5 mtorr . if the width of an air gap ( i . e ., the ratio of the air gap to a line - to - line space ) is increased , the upper end of the air gap becomes higher . the width and height of an air gap can be optimized by adjusting the thicknesses of the first and second interlevel dielectric layers 117 a and 117 b . next , the results of evaluation performed on the multilevel interconnect structure formed in this embodiment will be described . first , fig1 a through 12c will be referred to fig1 a illustrates a positional relationship between a line - to - line space and an air gap . in fig1 a , h denotes a distance between the upper surface of the first interconnect layer and the top of the air gap , and d denotes a distance between the lower surface of the first interconnect layer and the bottom of the air gap . the occupancy ratio r is the ratio of the width w of the air gap to the line - to - line space s . [ 0091 ] fig1 b illustrates the dependence of the occupancy ratio r of the air gap on the line - to - line space s . if s is equal to or smaller than 0 . 8 μm , the occupancy ratio r of the air gap is a positive value larger than zero . the smaller the line - to - line space s is , the larger the occupancy ratio r is . when s = 0 . 3 μm , the occupancy ratio r is about 0 . 9 . [ 0092 ] fig1 c illustrates the dependence of the distances h and d on the line - to - line space s . the value of h never exceeds 500 nm at any value of the line - to - line space s , and never reaches the cmp target level ( in the range from 800 nm to 1000 nm above the interconnect layer ). in other words , even after the interlevel dielectric film 117 has been planarized by a cmp technique , the air gap is not exposed . thus , the yield of the second interconnect layer does not decrease . next , it will be described with reference to fig1 how the line - to - line capacitance is effectively reduced in the multilevel interconnect structure formed in this embodiment . in fig1 , data about a conventional multilevel interconnect structure in which no air gaps are formed between adjacent lines is represented by open circles as a comparative example . in the comparative example , the smaller the line - to - line space is , the larger the line - to - line capacitance per unit length is . however , in this embodiment , as the line - to - line space decreases , the line - to - line capacitance also decreases to the contrary . the line - to - line capacitance decreases presumably because the occupancy ratio r of the air gap to the line - to - line space increases as the line - to - line space decreases . next , with reference to fig1 a and 14b , the reduction of the line - to - line capacitance in accordance with this embodiment will be compared to the reduction of the line - to - line capacitance accomplished by the use of an interlevel dielectric film having a low relative dielectric constant . [ 0095 ] fig1 a is a cross - sectional view illustrating the configuration of a model used for calculation ( or simulation ). fig1 b illustrates the dependence of an effective relative dielectric constant on a line - to - line space . the effective relative dielectric constant is determined by calculating the line - to - line capacitance ( per unit length ) generated when a uniform medium having a certain relative dielectric constant is used as the interlevel dielectric film and then by comparing the capacitance to the actually measured capacitance . as represented by the open squares in fig1 b , in this embodiment , the smaller the line - to - line space is , the smaller the effective relative dielectric constant is . if the line - to - line space is 0 . 8 μm or less , an air gap is formed in the line - to - line space . and if an air gap is formed , the effective relative dielectric constant drastically decreases . when the line - to - line space is 0 . 3 μm , the effective relative dielectric constant is as low as about 1 . 8 . [ 0096 ] fig1 illustrates a relationship between the resistance of an interconnecting metal ( i . e ., via resistance ) and the diameter of the interconnecting metal ( i . e ., via diameter ). as can be understood if this embodiment is compared to the comparative example in which no air gaps are formed , via resistance values are not different so much in both cases . [ 0097 ] fig1 illustrates the dependence of a via resistance value on an alignment error between the first interconnect layer and the interconnecting metal . the “ alignment error ” herein denotes the magnitude of the misalignment between the interconnecting metal and the first interconnect layer . since the width of a line - to - line space in the first interconnect layer is equal to the via diameter in the pattern used for measurement , there is no overlap margin between the first interconnect layer and the interconnecting metal . as can be understood from fig1 , in the conventional example , the larger the alignment error is , the higher the via resistance is . by contrast , in this embodiment , the via resistance remains substantially the same irrespective of the via resistance . the reason is as follows . even if misalignment has been caused , the contact area between the first interconnect layer and the interconnecting metal is kept at a maximum value , because the interconnecting metal always exists on the upper surface of the first interconnect layer . since the second interlevel dielectric film 117 is deposited after the interconnecting metal 109 has been formed , the air gaps , formed simultaneously with the deposition of the second interlevel dielectric film 117 , do not come into contact with the interconnecting metal 109 . accordingly , neither a shortcircuit failure between adjacent lines 113 a in the first interconnect layer 113 nor a shortcircuit failure between a line 113 a and the semiconductor substrate 101 is caused through the interconnecting metal 109 . the material of the first interconnect layer is not limited to al . alternatively , the first interconnect layer may be made of cu , for example . instead of a plasma oxide film , an applied insulating film , which can fill in a gap satisfactorily , may also be used as the second interlevel dielectric layer of the second interlevel dielectric film 117 . also , desirable effects can be attained even if the method for forming the second interlevel dielectric film , described with reference to fig1 c , is applied to any other embodiment of the present invention . according to the present invention , the first interconnect layer always exists under the entire bottom of the interconnecting metal . accordingly , even if misalignment has been caused during the formation of the first interconnect layer , it is possible to prevent a contact failure from being caused between the first interconnect layer and the interconnecting metal . in addition , the interconnecting metal is not filled into the air gaps that are formed simultaneously with the second interlevel dielectric film . thus , it is possible to prevent a shortcircuit failure from being caused between adjacent lines in the first interconnect layer or between a line and the semiconductor substrate through the interconnecting metal . if part or all of a line - to - line space is turned into an air gap or if the line - to - line space is entirely filled in with a material having a low relative dielectric constant , the relative dielectric constant between adjacent lines can be reduced at the line - to - line space . as a result , a semiconductor device , which operates with a larger margin and is less likely to operate erroneously , is realized by reducing a signal delay between the lines in the first interconnect layer . moreover , since most of the side face of the interconnecting metal is in contact with the second interconnect layer , reliability in connecting the interconnecting metal to the second interconnect layer can also be improved even if misalignment has been caused during the formation of the second interconnect layer . furthermore , even if misalignment has been caused during the formation of the first interconnect layer , either the interconnecting metal or the first interlevel dielectric film always exists on the upper surface of the first interconnect layer . in addition , the interconnecting metal is not filled into the air gaps that are formed simultaneously with the second interlevel dielectric film . thus , it is possible to prevent a shortcircuit failure from being caused between adjacent lines in the first interconnect layer or between a line and the semiconductor substrate through the interconnecting metal .	7
the present invention will be discussed hereafter in detail in terms of the preferred embodiment of the present invention with reference to the accompanying drawings . in the following description , numerous specific details are set for the in order to provided a thorough understanding of the present invention . it will be obvious , however , to those skilled in the art that the present invention may be practiced without these specific detail . in other instances , well - known structures are not shown in detail in order to avoid unnecessary obscurity of the present invention referring to fig1 , an electrical equipment ( not labeled ), such as a computer , according to the present invention comprises a motherboard and an electrical connector 100 mounted on the motherboard and exposed to access network through telephone line . the electrical connector 100 performs partial functions of an exiting modem card assembly . as best showing in fig2 in conjunction with fig1 , in the preferred embodiment of the invention , a digital insulation barrier ( combination of a safety insulation barrier and digital filters ) and a modem controller b are combined inside the electrical connector 100 . for convenience , such digital insulation barrier and the modem controller b integrated in the electrical connector 100 are referred to hereafter as modem components 33 ( shown in fig1 ). it should be noted that the existing modem card assembly is eliminated . the electrical connector 100 is mounted on the motherboard . at the same time functions of the modem controller a are moved onto the motherboard and associated with the modem components 33 of the electrical connector 100 . therefore , the main processor on the motherboard can access network directly through the electrical connector 100 and the telephone line . as a result the need in motherboard connectors is eliminated , additional significant cost reduction is achieved by reducing the size of the motherboard . it also should be noted that the digital insulation barrier and the modem controller a may selectively both be incorporated onto the motherboard , while only the controller b is integrated into the electrical connector 100 . referring to fig3 and 5 , the electrical connector 100 includes an insulative housing 1 , a plurality of conductive contacts 2 retained in the housing 1 , an electrical element 3 containing the modem component 33 performing partial functions of the existing modem card assembly , a connector module 4 ( shown in fig4 ), a plastic rear cover 5 and an outer shell 6 substantially surrounding and shielding the housing 1 . referring to fig6 and 7 , the insulative housing 1 includes a mating face 11 , an upper wall 12 , two sidewalls 13 and a rear opening 14 . the mating face 11 provides upper and lower cavities 111 , 112 extending rearwardly thereinto . the rear opening 14 shares a panel 15 with the lower cavity 112 . in the embodiment illustrated , the upper cavity 111 is a modular plug - receiving cavity for mating with a modular plug connector , and the lower cavity 112 is provided for receipt thereinto of the connector module 4 . the upper cavity 111 provides a plurality of barriers 113 projecting inwardly from the mating face 11 , and a number of ramps 115 essentially aligned with and spaced from corresponding barriers 113 in a longitudinal direction , thereby forming a plurality of parallel slots 114 between the adjacent barriers 113 and the ramps 115 in a front - to - rear direction for receiving corresponding contacts 2 . a plurality of grooves 117 are dimensioned to be positioned proximate the panel 15 and communicating with the rear opening 14 for receiving the contacts 2 . the housing 1 further includes a plurality of comb passages 116 extending into the upper cavity 111 and communicating with the rear opening 14 . the upper wall 12 defines a pair of locking holes 121 far from the mating face 11 . each sidewall 13 has a shaft 131 projecting inwardly from a bottom portion thereof for engaging with the plastic rear cover 5 . as best shown in fig8 , the conductive contacts 2 are initially attached to a carrier strip 24 . each conductive contact 2 includes a base portion 21 having a front nose 211 on a front section thereof , a contacting portion 22 upwardly and rearwardly extending from the front nose 211 of the base portion 21 and a tail portion 23 connected to the carrier strip 24 . the base portion 21 has a pair of shoulders 212 adjacent to the front nose 211 and extending transversely from opposite sides thereof . the base portion 21 further has an enlarged section 213 apart from the front nose 211 and extending transversely and outwardly . the tail portion 23 is integrally attached to the enlarged section 213 by a transition bight 24 . the tail portion 23 downwardly offsets from the transition bight 24 and is parallel to the base portion 21 . the tail portion 23 has a positioner section 231 extending from opposite sides thereof adjacent to the transition bight 24 . referring to fig1 and 12 , the electrical element 3 includes an internal circuit board 31 carrying the modem components 33 and a plurality of footer contacts 32 thereon . the internal circuit board 31 provides a plurality of pinouts 311 on a substantial middle portion thereof for respectively receiving the contacts 2 and a plurality of footer holes 312 in a lower portion thereof . each footer contact 32 has a latch beam 321 extending horizontally from a top portion thereof and interferentially fitted in the corresponding footer holes 312 . it should be noted that the footer contacts 32 are initially attached to a carrier strip 34 . the carrier strip 34 is removed from the footer contacts 32 after or before the footer contacts 32 are installed in the internal circuit board 31 and soldering thereto . the internal circuit board 31 further has a number of signal conditioning components mounted thereon ( not labeled ). such signal conditioning components can be passive electrical components such as transformers , resistors , capacitors and as such , and active components such as varistors , thyristors , transistors and integrated circuits , and electromechanical components such as switches , relays , indicators and transient voltage suppressors . referring to fig4 and 5 , the plastic rear cover 5 includes a vertical portion 51 and a horizontal portion 52 extending forwardly from a bottom side of the vertical portion 51 . the vertical portion 51 includes a pair of projections 53 extending from a top end thereof and a pair of fixing portions 54 formed near opposite sides of a bottom end thereof . the projections 53 are provided for latching within the locking holes 121 of the housing 1 , respectively . the fixing portions 54 are provided for engaging with the corresponding shafts 131 of the housing 1 . the outer shell 6 is stamped from a sheet of conductive material and includes a front shell 61 and a rear shell 62 which mount together to define an interior space for enclosing the housing 1 . the front shell 61 includes a front plate 611 providing two windows ( not labeled ) respectively corresponding to the upper and lower cavities 111 , 112 , and two side plates 612 . each side plate 612 has a plurality of embossments 613 and a plurality of grounding tabs 614 extending downwardly from a bottom end thereof . the rear shell 62 has a number of apertures 621 corresponding to and engaging with respective ones of the embossments 613 . referring to fig9 and 10 in conjunction with fig8 , in assembly , the conductive contacts 2 are installed in the housing 1 from the rear opening 14 . the front nose 211 of each contact 2 extends through respective one of the passages 116 and is received in the corresponding slot 114 . the contacting portion 22 of each contact 2 is exposed in the upper cavity 111 with a free end deflected by the corresponding passage 116 , thereby having a preload force . the base portion 21 and the front nose 211 of each contact 2 are held in the slot 114 . the shoulders 212 of each contact 2 are latched with the raised ramps 115 , in conjunction with the contact preload force which keeps a constant downward force on the contacts 2 , thereby assuring that the contacts 2 don &# 39 ; t lift off the shoulders at the end of the ramps . the positioner sections 231 of the contacts 2 are received in the grooves 117 . therefore , the contacts 2 are securely embedded in the housing 1 . after installation , the carrier strip 24 is removed from the contacts 2 . referring to fig4 and 5 in conjunction with fig3 , the electrical element 3 is attached to the housing 1 from the rear opening 14 . the tail portion 23 of each contact 2 extends beyond the grooves 117 and into the respective one of the pinout 311 of the internal circuit board 31 . the plastic rear cover 5 is coupled to the housing 1 . the shafts 131 of the housing 1 are installed in the fixing portion 54 of the plastic rear cover 5 . the projections 53 of the plastic rear cover 5 are received in the corresponding locking holes 121 of the housing 1 , thereby stabilizing the connection between the contacts 2 and the internal circuit board 31 . the connector module 4 such as a dual usb module for mating with usb type plugs , is assembled to the lower cavity 112 of the housing 1 from the mating face 11 . the structure and the function of the connector module 4 is well known to those skilled in the art , a detailed description thereof is omitted herefrom . the outer shell 6 substantially surrounds the housing 1 . the front plate 611 of the front shell 61 affixes along the mating face 11 of the housing 1 . the embossments 613 are interference fitted in the respective one of the apertures 621 . the grounding tabs 614 are soldered to the corresponding grounding holes ( not shown ) of the motherboard . it is to be understood , however , that even though numerous , characteristics and advantages of the present invention have been set fourth in the foregoing description , together with details of the structure and function of the invention , the disclosed is illustrative only , and changes may be made in detail , especially in matters of shape , size , and arrangement of parts within the principles of the invention to the full extent indicated by the broad general meaning of the terms in which the appended claims are expressed .	7
in accordance with the invention , a composition for deicing or inhibiting the formation of ice comprises ( a ) between about 1 . 0 and about 99 % by weight waste material from a fermentation process for producing an amino acid from a carbohydrate source used as an anti - freezing and deicing agent ; ( b ) between about 0 . 0 and about 99 % by weight of a second anti - freezing and deicing agent ; and ( c ) between about 0 . 0 and about 60 % by weight of a carrier . the fermentation process relies upon the use of microbes that synthesize the desired amino acid from the carbohydrate source . the microbes may be genetically altered to better perform this function and include bacteria from various genera . in one particularly useful embodiment of the present invention , the amino acid is selected from a group consisting of glutamic acid and lysine . glutamic acid may be produced by bacteria from the genera bacillus , micrococcus , brevibacterium microbacterium , corynebacterium anthrobacter and the like . corynebacterium glutamicum and related strains are useful in producing lysine . it should be appreciated , however , that other microorganisms useful in producing glutamic acid of lysine by means of fermentation of a carbohydrate source may be used . the carbohydrate source may be any such source known to be useful in the production of the desired amino acid by means of microbial fermentation . carbohydrate sources include , but are not limited to , cassava , raw sugar , starch , starch hydrolysate , molasses , desugared molasses , corn sugar molasses , sugar beet molasses , sugar cane molasses , desugared sugar beet molasses and mixtures thereof . in one possible production process known in the art , a starch from cassava is hydrolized . after the starch processing stage , molasses is added during a syrup refining stage . after this stage , glucose syrup is added and the mixture proceeds to a fermentation stage . during the fermentation stage , ammonia and micro - organisms , in this case bacteria , are added for microbial fermentation . the bacteria are grown in a liquid medium containing molasses as the fermentation substrate . glutamic acid producing bacteria produce and excrete glutamic acid into the medium . alternatively , lysine producing bacteria may be used to produce and excrete lysine into the medium . as a consequence of fermentation , all or substantially all of the sugar in the substrate is used . subsequently , the glutamic acid / lysine is separated from the medium by evaporation and neutralization ( addition of sodium hydroxide and hydrochloric acid ). the glutamic acid / lysine then goes through another stage of neutralization , followed by filtration and crystallization . the glutamic acid / lysine is then dried , sieved and packaged . the leftover byproduct or waste material from the fermentation process , sometimes referred to as condensed molasses fermentation solubles ( cms ), is an active ingredient in the deicing composition of the present invention . the waste material of the fermentation process exhibits enhanced deicing properties and is non - corrosive . the waste material is approximately sixty percent ( 60 %) solids , but may vary depending on the process . the carrier is typically water although any other appropriate carrier suitable for use in a deicing composition including fermentation waste material may be used . the resulting composition is easily sprayed or applied to surfaces in need of deicing or where there is a desire to prevent freezing ( such as roads , bridges , sidewalks , vehicles , machines , crops , aggregate piles , or the like ). the second anti - freezing and deicing agent may , for example , be selected from a group of material consisting of sugar cane molasses , sugar beet molasses , desugared sugar beet molasses , or organic agricultural byproducts . alternatively , the second anti - freezing and deicing agent may be selected from a group consisting of calcium chloride , magnesium chloride , sodium chloride , potassium chloride , sodium formate , sodium acetate , potassium acetate , ethylene glycol , diethylene glycol . the second anti - freezing and deicing agent may be in solid form ( granular ) or solution brine ) form . the first deicing agent serves to enhance the deicing properties and reduce the corrosive nature of these second anti - freezing and deicing agents . the weight percentages of the various ingredients of the composition are selected and mixed as desired in order to tailor the deicing properties of the composition to any particular application . in accordance with yet another aspect of the present invention , it should be appreciated that the fermentation waste material deicing agent , can be used without further additions ( 100 % or neat ), which is desirable in terms of providing a completely natural deicing product . alternatively , the fermentation waste material may be mixed with additional materials including , for example , water , anti - skid agents such as sand , cinders , etc . forming a composition in the range of 1 - 80 % solids by weight , depending on the application . the following detailed examples illustrate experiments which demonstrate the improved properties and characteristics of the compositions of the present invention . of course , these examples are provided for purposes of illustration only and are not intended to be limiting . the objective of the first experiment was to determine the corrosiveness of various fermentation waste materials on metals . initially , used steel nails were cleaned with an aqueous solution of muriatic acid ( better known as hydrochloric acid , hcl ). subsequently , the steel nails were inserted into different solutions of fermentation waste materials ( fwm ) for thirty days to study the corrosive effects the solution had upon the steel nails . the results of the experiment of displayed in the table below : as shown in the table , the 10 %, 20 % and 30 % fwm solutions by weight did not show any corrosive effect on the steel nails in thirty days . the objective of the second experiment was to determine whether various fmw solutions would freeze under freezing conditions . fmw solutions ranging between 10 % and 50 % solids by weight were placed into freezing conditions . in particular , these solutions were placed into a freezer at 32 ° f . ( 0 ° c .) to study whether the solutions would freeze . the 10 % and 20 % solids by weight fmw solutions froze the first day . the 30 % solids by weight fmw solution by weight became “ slushy ” on the first day . specifically , some freezing was observed , but the solution remained primarily in its liquid state . the 40 % and 50 % solids by weight fmw solutions did not freeze over the thirty day period . based upon the experimentation , no increase in freeze point of the various fmw solutions was observed . further , no dilution of the fmw solutions was observed throughout the testing . the foregoing description of a preferred embodiment of the invention has been presented for purposes of illustration and description . it is not intended to be exhaustive or to limit the invention to the precise form disclosed . obvious modifications or variations are possible in light of the above teachings . the embodiment was chosen and described to provide the best illustration of the principles of the invention and its practical application to thereby enable one of ordinary skill in the art to utilize the invention in various embodiments and with various modifications as are suited to the particular use contemplated . all such modifications and variations are within the scope of the invention .	2
in the following description , numerous specific details are set forth to provide a more thorough understanding of the present invention . however , it will be apparent to one of skill in the art that the present invention may be practiced without one or more of these specific details . in other instances , well - known features have not been described in order to avoid obscuring the present invention . fig1 illustrates a system 100 configured to implement one or more aspects of the present invention . the system 100 includes , without limitation , a central processing unit ( cpu ) 130 , a system memory 110 , a graphics processing unit ( gpu ) 115 , a device / memory bridge 105 , a network interface 145 , a digital pen 135 , and a spatially - aware projector 132 . the spatially - aware projector 132 is configured to be grasped by a non - dominant human hand while the digital pen 135 is configured to be grasped by a dominant human hand . the cpu 130 communicates with the system memory 110 via the device / memory bridge 105 , which may be , e . g ., a northbridge device or subsystem . system memory 110 is configured to store application programs , as well as data used by or generated by the cpu 130 . in particular , system memory 110 is configured to store design data 150 , such as computer - aided design drawings and information that is accessed by the application program 112 . system memory 110 is also configured to store image data 155 for display by the spatially - aware projector 132 . the image data 155 may be produced by the cpu 130 or a discrete gpu 115 based on design data 150 and / or data received via the spatially - aware projector 132 and the digital pen 135 . system memory 110 is coupled to the device / memory bridge 105 via a system memory bus 150 . the device / memory bridge 105 may be coupled to the gpu 115 that incorporates real - time image rendering means for rendering both three - dimensional ( 3d ) and two - dimensional ( 2d ) images . the cpu 130 or gpu 115 delivers pixel data to the spatially - aware projector 132 . in some embodiments , the integrated circuit implementing the cpu 130 may incorporate additional functional blocks , such as the device / memory bridge 105 and gpu 115 . the device / memory bridge 105 is also coupled to the network interface 144 , the digital pen 135 , and the spatially - aware projector 132 . the network interface 144 provides network connectivity to other computers in local or remote locations using any suitable technology , preferably a wireless technology . in particular , portions of design data 150 and image data 155 may be output to remote users via the network interface 144 . similarly , data received from a remote user via the network interface 144 may be displayed and / or stored as design data 150 or image data 155 . other components ( not explicitly shown ), including usb or other port connections , cd drives , dvd drives , film recording devices , and the like , may also be connected via network interface 145 . communication paths interconnecting the various components in fig1 may be implemented using any suitable protocols , such as pci ( peripheral component interconnect ), pci express ( pci - e ), agp ( accelerated graphics port ), hypertransport , quick path interconnect , or any other bus or point - to - point communication protocol ( s ), and connections between different devices may use different protocols as is known in the art . in one embodiment , system memory 110 is configured to store a graphics modeling or authoring application program 112 that is configured to access the design data 150 to provide image data 155 for display via spatially - aware projector 132 and use information acquired by the digital pen 135 and the spatially - aware projector 132 to display a user - interface or image data . fig2 illustrates a detailed view of the digital pen 135 according to one embodiment of the present invention . as shown , the digital pen 135 includes a force sensor 202 , which indicates when the tip of the digital pen 135 is in contact with a display surface 208 and may be used to record pen strokes . an ink reservoir may be configured to deposit physical ink on the display surface when the tip of the digital pen 135 is in contact with a surface . a camera 204 is also included in the digital pen 135 and is positioned to enable 2d tracking using patterns printed on the display surface 208 . in one example , dot - pattern technology is used to provide the 2d tracking , where a unique dot pattern 212 is identified by camera 204 while scanning area 210 . the camera 204 may also be used to enable 3d optical tracking using traceable patterns to retrieve camera calibration parameters to determine 3d location and orientation . the patterns may also represent a hierarchical encoding pattern which allows the camera to cover a wide range of distances from the display surface 208 . additional patterns may be printed on the display surface 208 in infrared ink to be less distracting to the user . in other embodiments , the digital pen 135 may include alternative tracking mechanisms to the camera 204 . for example , any type of proximity sensor , e . g ., electromagnetic sensors may be included in the display surface 208 to detect a location of digital pen 135 . this configuration would advantageously enable the spatially aware projector 132 to be lifted a substantial distance from the display surface 208 while maintaining overall functionality and providing a larger projected image onto the display surface 208 . an input mechanism 206 is further included in digital pen 135 and may be implemented using a button that is configured to be activated and / or deactivated by a user , as described in further detail herein . fig3 a - 3b illustrate a detailed view of the spatially - aware projector 132 according to one embodiment of the present invention . in order for the spatially - aware projector 132 to display the design data 150 and / or image data 155 as a visual overlay in the context of a paper document , the application program 112 needs to be aware of the spatial location of the spatially - aware projector 132 and the digital pen 135 relative to the display surface 208 . capturing the location of the spatially - aware projector 132 and / or the spatially - aware pen 135 on the display surface 208 allows the spatially - aware projector 132 to display virtual information which is relevant to the existing physical content on the paper . the virtual information may be read from design data 150 or information previously captured by digital pen 135 from pen strokes stored as image data 155 . the digital pen 135 increases the user &# 39 ; s ability to work with functionality that requires visual feedback , such as viewing the results of computations , and overlaying contextual information onto the digital paper 208 via spatially - aware projector 132 . in one embodiment , the spatially - aware projector 132 includes a handle 302 , a scroll wheel 304 , a digital pen 135 1 , a digital pen 135 2 , a micro - projector 306 , a small mirror 308 , a swivel handle 310 , and a large mirror 312 . the handle 302 may be grasped by a hand of the user to navigate the spatially - aware projector 132 across the display surface 208 . the scroll wheel 304 may be implemented using a scroll wheel of a mouse , and is used to , e . g ., cause elements included within a projected image 314 to be scaled up or down . the projected image is dynamically updated to display virtual layers , as described in further detail below in conjunction with fig6 . input received via digital pens 135 1 and 135 2 provides both a position and angle of the projector with respect to the display surface 208 . in other embodiments , alternative tracking mechanisms may be included within the spatially - aware projector 132 , such as the proximity sensors described above in conjunction with fig2 . projected image 314 is displayed via micro - projector 306 , small mirror 308 and large mirror 312 . the angle of large mirror 312 is adjustable via the swivel handle 310 to increase or decrease the size of the projected image 314 . in this way , a user of system 100 is advantageously able to focus his or her work across a small or large portion of display surface 208 , as illustrated in fig3 b . note that the position of micro - projector 306 and small mirror 308 are not fixed and may also be adjusted , either alone or in combination , to influence projected image 314 . in addition , if a laser - based pico projector is used , the scanning pattern produced by the pico projector may be modified to reduce artifacts that are often visible when the large mirror 312 is angled to increase the size of the projected image 314 . for example , the spatially - aware projector 132 may include a mechanical controller , that , when adjusted , changes the spread between each raster line that is produced by the laser - based pico projector . this may be accomplished , for example , by modulating x and y axis - based oscillating mirrors that relay the laser beam to different x , y coordinates of the large mirror 312 . moreover , the oscillating frequency of these can be modified on demand using acousto - optic modulators . as a result , the artifacts may either be reduced or eliminated entirely . fig4 illustrates an independent input / output technique 400 according to one embodiment of the present invention . as shown , the spatially - aware projector 132 produces a projected image 402 on display surface 208 . the location and orientation of the spatially - aware projector 132 and the digital pen 135 with respect to display surface 208 is carefully considered , since they affect the overall operation of the system in several ways . digital pen 135 3 provides a direct link between input , e . g ., pen strokes , illustrated as virtual input 404 , and output , e . g ., projected image 402 . importantly , decoupling the digital pen 135 and spatially - aware projector 132 allows for independent input and output . for example , the projected image 402 can be stationary while the digital pen 135 is used . in other words , the digital pen 135 and the spatially - aware projector 132 can be operated simultaneously and independently from one another . additionally , multiple users may share the same display surface 208 and collaborate by each providing input via additional spatially - aware digital pens 135 4 - x . remote users may also provide input and see the same projected image 402 on a remote display surface 208 . fig5 illustrates a displaced input technique 500 according to one embodiment of the present invention . another property resulting from decoupling the digital pen 135 and spatially - aware projector 132 is the capability to provide input via the digital pen 135 outside of the projected image 402 . for example , the user can write a “ search ” keyword via displaced virtual input 502 outside the projected image 402 on a separate display surface 208 2 and the search results can be included in the projected image 402 . furthermore , users can interact with the projected image 402 on a separate display surface 208 to interact with virtual display elements located thereon . fig6 illustrates different virtual layers , according to one embodiment of the present invention . the display layers include the physical display layer 260 and the virtual display layer ( s ) 265 . the virtual display layers 265 may include multiple separate virtual layers that are overlaid . each virtual layer may include one or more of user printout database layers 270 , user database layer 275 , and / or viewport layer 280 . the physical display layer 260 is the layer which physically exists on the display surface 208 and may include a variety of different elements . examples of elements include printed content , such as a diagram or two - dimensional building layout , ink created by the user , and user interface elements , such as menus and icons , preprinted on the physical display layer 260 . above the physical display layer 260 are one or more virtual display layers 265 that may be combined to produce the projected image 402 . a variety of display elements may be projected onto the virtual display layers 265 . printout database layer 270 contains auxiliary data that is displayed in the context of the printed content . for example , if a map is printed on a piece of paper , the printout database consists of vector images and text labels of either printed content or electronically stored content . display elements within the printout database layer are locked on - surface and aligned with the underlying printout . printout database layer 270 may be useful for displaying aspects of the design data 150 that are not included in the physical display layer 260 . for example , when multivalent documents that consist of multiple abstract layers of distinct — but closely coupled content — are used , then only some of the abstract layers may be included in physical layer 260 . multivalent documents are especially prevalent in the application domain of architecture and three - dimensional modeling , e . g ., different floor plans , section views , and additional metadata to describe materials and processes . user database layer 275 includes any new virtual display element , which is added by the user . for example , when a user creates ink ( annotation or sketching ) on top of the paper , the stroke is inserted into this layer . the contents of this layer are also locked on - surface . the most basic functionality of the digital pen 135 is creating virtual and / or physical ink . the digital pen 135 enables users to create and manage virtual ink that users can then make use of in different functions , such as tracing and drawing virtual guides . in some embodiments , the input mechanism 206 is used to change from a pen tip with physical ink to a pen tip using virtual ink that is displayed within the projected image 402 . when virtual ink is enabled , all pen strokes are added to the virtual ink display layer 265 , in the location of the display surface in which they are created . the user database layer 275 may be stored in image data 155 or design data 150 . hence , the annotations are added to only the virtual display layer 265 . this allows a user to annotate a blueprint without altering the original document . users can trace over both physical and virtual content within projected image 402 to produce trace data that is captured and stored in image data 155 . the trace data may be applied to different special locations within the display surface 208 . users may also load existing virtual templates to trace out with physical ink input . the resolution and size of the virtual content being traced may be adjusted via , e . g ., the scroll wheel 304 , or by displaying a virtual menu in projected image 402 that may be navigated using a digital pen 135 . instead of tracing , virtual guides may be created to aid in generating a physical sketch . such grids and guides are widely used in image editing applications , but unavailable when working on physical paper . to create a geometric guide , the user can select the line circle , rectangle , or grid menu display element , as described in further detail below in conjunction with fig7 . instead of entering points that define the geometry , the user may draw a similar shape and the digital pen 135 will approximate the selected shape . for example , the user can draw a circle using the digital pen 135 on the display surface 208 , and the location of digital pen 135 relative to the display surface 208 determines the center point and the radius . in grid mode , users may draw a rectangle that serves as the unit rectangle shape of the grid . once the digital pen 135 is lifted , the entire virtual layer is covered with a self replicating grid layout . viewport layer 280 contains global user - interface controls that enable a user to change the settings of the printout database layer 270 and the user database layer 275 . to keep these elements available at all times , viewport layer . 280 is not bound to a specific location of the display surface 208 but instead locked in - hand . note that the printout database layer 270 and user database layer 275 are page - dependent while the viewport layer is application - dependent . hence , when the digital pen 135 and / or spatially - aware projector 132 are placed on a different page , the spatially - aware projector 132 displays different content , but the same user - interface controls . an exemplary user - interface is described in detail below in conjunction with fig7 . fig7 illustrates a user interface 700 that is projected onto display surface 208 according to one embodiment of the present invention . as shown , user interface 700 is included in projected image 402 and allows for display , combination , and / or manipulation of the virtual display layers 265 displayed within the interaction region 706 . to access and control system features , the spatially - aware projector 132 displays the user interface 700 . to manipulate virtual content displayed within projected image 402 , contextual marking menus can be displayed within the viewport layer 280 , thereby providing the user with a diverse set of command execution options . the user interface 700 includes one or more database layer toolbar 702 icons 704 in the top border of the projected image 402 , and one or more icons 710 in the toolbar 708 included in the bottom border of the projected image 402 . the database layer toolbar 702 allows users to toggle the visibility of the printout database layer 270 and the user database layer 275 . additionally , touching and holding the digital pen 135 to the display surface 208 causes a marking menu ( not shown ) to be displayed within interaction region 706 and enables selection of various menu display elements , as described in further detail below in conjunction with fig8 a - 8b . for example , if working with a college campus map , layers such as “ library ”, “ dining ”, and “ overview ” could be menu display elements in the marking menu that could be activated or deactivated . icons 710 included in toolbar 708 may be used to , e . g ., modify colors of virtualized data , copy and paste virtualized data , perform search functions , enable camera view , and / or operate drafting tools , as described in further detail below . fig8 a illustrates a dominant hand menu selection 800 performed via a radial menu 802 that is included in projected image 402 according to one embodiment of the present invention . the radial menu 802 may be implemented using hierarchy to access various functions of the system . the radial distribution of menu display elements in regions 802 , 804 , 806 , and 808 that are separated by region boundaries , e . g ., region boundary 810 , simplifies use of the radial menu 802 since users only need to remember what direction to move towards . here , a virtual cursor is bound to the tip of the digital pen 135 , and is used to control the selection of regions 802 , 804 , 806 and 808 . users can access the radial menu 802 , e . g ., by activating the input mechanism 206 on digital pen 135 to cause the top level of the radial menu 802 to be displayed in virtual display layers 265 . in contrast , conventional digital pen menu systems rely on menus that are preprinted on the display surface . the user can select a menu display element in two ways , as illustrated in fig8 a - 8b . the first method involves a dominant hand menu selection technique 800 , where the user can use a traditional method of moving the digital pen 135 in the direction of the menu display element , as illustrated in fig8 a . alternatively , the user can use a non - dominant hand menu selection technique 850 , illustrated in fig8 b . here , user instead moves the spatially - aware projector 132 with the non - dominant hand ( i . e ., the hand that is not holding the digital pen 135 ) in the opposite direction of the menu display element while keeping the digital pen 135 fixed and pressed against the display surface 208 , thereby repositioning the menu display element under the pen tip . advantageously , the non - dominant hand menu selection technique 850 allows users to perform menu display element selections without leaving a physical ink trail on the display surface 208 . fig9 illustrates a display surface 208 that includes a floorplan that is overlaid with a projected image 900 that displays virtual content according to one embodiment of the present invention . the projected image 900 includes electrical components 902 . note that the electrical components 902 are only visible within the projected image 900 . in other embodiments , the projected image 900 may include additional components or additional layers , e . g ., heating , ventilation , mechanical , lighting , and the like . the overlaid content or the original physical content may be copied to another location on display surface 208 to be overlaid . the user enters a copying mode using the radial menu 802 and indicates an area using the digital pen 135 to specify a contextual parameter of the projected image 900 or the image printed on the display surface 208 . the user then enters a pasting mode using the radial menu 802 , and the copied content is displayed using the locked in - hand metaphor and copied when the user engages the input mechanism 206 . fig1 illustrates a display surface 208 that includes a floorplan that is overlaid with a projected image 1000 that hints at virtual content according to one embodiment of the present invention . the virtual display layers 265 enable computations to be performed and the results displayed in the contexts of the user &# 39 ; s workspace . the user may perform a measurement query by selecting a particular element to be measured using the spatially - aware projector 132 and / or digital pen 135 and engaging a dimension tool to overlay the measurement information . using the radial menu 802 , the user can choose to measure a distance , path length , area , or volume . alternatively , the user may create a line or bounding box using the digital pen 135 , where the measurements of the line or bounding box are displayed in the projected image 1000 . the measurement computation is displayed by the spatially - aware projector 132 within the projected image 1000 . a search command may allow users to search for elements that exist within the virtual display layers 265 . the user can perform the query in two ways . first , they can choose from a list of query elements , e . g ., sprinklers , outlets , and the like , in the search menu provided by the radial menu 802 as described above . alternately , the user can directly select an instance of an element on display surface 208 or within projected image 1000 using the digital pen 135 . for example , the user may perform a query to search for electrical outlets . in response , the outlets 1002 — which are outside of the projected image 1000 — are hinted to by halos 1004 , where each halo corresponds to an outlet that is nearby , but not within , the projected image 1000 . halos 1004 may guide the user to additional instances of the element that was searched , allowing the user to find elements of interest faster . the user can also adjust the swivel handle 310 to increase the size of the projected image 1000 to navigate toward or to display the elements corresponding to one or more of the halos 1004 . alternatively , the user can relocate the spatially - aware projector 132 perform the navigation . fig1 illustrates a display surface 208 that is overlaid with a projected image 1100 that includes a color palette 1104 according to one embodiment of the present invention . here , each section of the color palette 1104 includes a unique border color . to change the property of a virtual display element , e . g ., an electrical component 1102 , the user first aligns the color palette 1104 on top of a display element included in printout database layer 270 . then , the user can tap on the electrical component 1102 through the color palette 1104 to change the color of the electrical component 1102 . to simplify the manipulation , the color palette 1104 can be resized via scroll wheel 304 . the color palette 1104 can also be relocated within projected image 1100 via a handle attached to the color palette 1104 . fig1 illustrates a display surface 208 that is overlaid with a projected image 1200 that includes a stencil 1202 according to an embodiment of the present invention . here , the stencil 1202 is representative of any drafting tools that are used to guide a user when he or she is drawing across the display surface 208 using a digital pen 135 . like the color palette 1104 , the stencil 1202 is resizable via the scroll wheel 304 . in addition to the virtual ink that can be used to trace drawings , drafting and measurement palettes can also be used as virtual “ stencils ” that help users guide their physical pen strokes ( i . e ., ink strokes ). in one embodiment , these stencils include rectangle and circle shape tools , a protractor , and french curves . fig1 illustrates generating a video walk - through of an environment based on strokes generated by a user via a digital pen 135 according to one embodiment of the present invention . the user may draw a path , such as walkthrough path 1300 , on the display surface 208 with the digital pen 135 . frames of the two - dimensional walk - through represented as pixel data , as viewed from a viewpoint moving along the walkthrough path 1300 , are generated by the cpu 160 or the gpu 115 and stored in the image data 155 for playback as a walk - through animation . the playback may be projected onto the display surface 208 by the spatially - aware projector 132 and / or played back on alternative output devices , e . g ., a liquid crystal display ( lcd ) monitor . as the frames are being displayed via spatially - aware projector 132 , the position 1302 indicates the position along the walkthrough path 1300 that corresponds to the current frame that is displayed . additionally , the walkthrough path 1300 and position 1302 may be used as a slide bar and slide bar position interface element , respectively , for the user to navigate a corresponding frame that he or she desires to view . fig1 illustrates an in - place copy / paste technique 1400 according to one or more embodiments of the invention . as described above in conjunction with fig4 , independent input and output allows users to select different parts of the viewport layer 280 and to easily select menu display elements . when the copy and paste feature is activated , the user can use the viewport layer 280 as a clipboard to copy a display element , e . g ., an electrical component 902 , from one location to another within a display surface 208 that includes electrical component 902 , or in another display surface 208 . there are two steps involved when copying an display element from one location of a display surface 208 to another location . the user first copies the display element from the database layer 275 to the viewport layer 280 . then , users paste the display element into the desired location of the user database layer 275 by using in - place copy / paste technique 1400 or displaced copy / paste technique 1500 described in further detail below in conjunction with fig1 . when performing an in - place copy / paste technique 1400 , the object selection occurs within the viewport layer 280 , and the in - place paste can occur from the database layer 275 to the viewport layer 280 thereby , which creates a hyperlink between the virtual display elements . the spatially - aware projector 132 is then repositioned to a desired paste location , whereupon the user can paste the copied display element from the viewport layer 280 to the database layer 275 . fig1 illustrates a displaced copy / paste technique 1500 according to one or more embodiments of the invention . as illustrated , when a display element that lies outside of the projected image 402 is selected , the displaced copy / paste technique 1500 is used . when the display element is selected and copied with the digital pen 135 , its virtual representation is copied to the viewport layer 280 , and an active hyperlink is created as described above . this active hyperlink enables the user to select the display element again using the dominant hand to access a contextual marking menu for the copied display element , where the contextual marking menu is displayed in the viewport layer 280 . selecting a paste submenu display element will paste the display element to the user database layer 275 . display elements can be copied from one layer to another because different contextual marking menus are shown depending on the underlying information layer . for example , if display elements are located in the user database layer 275 , then a menu containing “ copy ” pops up so that the printout database layer 270 can be used as source of copy . similarly , if a display element is located inside the viewport layer 280 , a menu containing “ paste ” pops up . when the user transfers display elements to the viewport layer 280 or to the user database layer 275 , different types of representations can be selected . the user may copy its raw digital representation using a “ shape ” submenu . if the user wants to copy an iconic representation that displays meta - data such as the direction to its original location within the display surface 208 , the user can select an “ icon ” submenu . for error management , users can correct and undo their copy and paste operation using different techniques . in one example , users can select a “ delete ” submenu on display elements in user database and viewport layers . in another example , the user can reposition display elements within the viewport layer using the “ move ” submenu . note that users can either move the digital pen 135 , or move the spatially - aware projector 132 to change the relative location of the display element in the viewport coordinate system . in - place and displaced manipulations are also available in the search functions described herein . when the search feature is activated , the user can execute a search by either writing or clicking the display element to be searched inside the projection area ( in - place ) or outside the projection area ( displaced ). when the user writes the display element to be searched , the pen strokes are gathered and translated into text that the cpu 130 is able to interpret . for example , if the user writes “ wireless ” on a separate display surface 208 , and the projector is placed on top of a display surface 208 that corresponds to a college campus , then buildings with wireless support will be highlighted . if the projector is placed on top of a document , a text bounding box of the search results will be highlighted . if the result is inside the viewport , then the result is simply highlighted with an outline . if the result is outside the viewport , the halo technique may be used as described above in conjunction with fig1 . there are a variety of ways to initiate a search . for example , users can write a keyword , or lasso a phrase already written as part of an annotation , or lasso printed text . the search considers not only the printout database layer 275 but also display elements on the user database layer 275 that the user may have added while during previous interactions with a corresponding display surface 208 . fig1 illustrates a flow diagram of method steps 1600 for performing a copy and paste function according to one embodiment of the invention . the method begins with step 1602 where the user selects the overlay data to be displayed in the projected image 402 . the data may be selected using the projected radial menu 802 . at step 1604 , the application program 112 updates the overlay data in the projected image 402 via the spatially - aware projector 132 . at step 1606 , the user activates a copy mode . at step 1608 , the user selects a region or an element within the display surface 208 or the projected image 402 . at step 1610 , the application program 112 stores in memory within image data 155 an image of the copied region or element . at step 1612 the user selects a paste position within the display surface 208 using the spatially - aware projector 132 . at step 1614 , the application program 112 updates the overlay image to include the copied region or element . at step 1618 the updated overlay image is displayed via the spatially - aware projector 132 , whereupon the user is able to complete the paste function as described above . fig1 illustrates a flow diagram of method steps 1700 for displaying overlay data for a computation according to one embodiment of the invention . the method begins at step 1702 where the user selects a region or element on display surface 208 or within projected image 402 using the digital pen 135 . at step 1704 , the application program 112 obtains the data corresponding to the selected region or element . at step 1706 , the application program 112 performs one or more computations specified by the user . at step 1708 , the application program 112 updates the overlay image to include the computation result . at step 1710 , the updated overlay image is displayed via the spatially - aware projector 132 . the printed content that is visible on the display surface is only one abstract view of a larger electronic file that is stored in the design data 150 within system memory 110 . for example , when a two - dimensional floor plan is printed on the display surface 208 , the digital pen 135 may directly access a highly detailed three - dimensional model that is stored as the design data 150 or image 155 or generated by the cpu 130 or gpu 115 using the design data 150 . a view of the three - dimensional model may be displayed within the projected image 402 that is output by the spatially - aware projector 132 . the printed content that is visible on the display surface is only one abstract view of a larger electronic file that is stored in the design data 150 within system memory 110 . for example , when a two - dimensional floor plan is printed on the display surface 208 , the digital pen 135 may directly access a highly detailed three - dimensional model that is stored as the design data 150 or image 155 or generated by the cpu 130 or gpu 115 using the design data 150 . a view of the three - dimensional model may be displayed within the projected image 402 that is output by the spatially - aware projector 132 . in sum , the spatially - aware projector and digital pen enable the use of virtual ink in addition to conventional physical ink . the virtual ink may be used to capture commands , annotate an existing design , and communicate with a remote user . the virtual ink may be displayed as a projected image on a display surface by the spatially - aware projector . auxiliary design information and rendered images may also be displayed in the projected image . the spatially - aware feature of the projector and digital pen allows for gestures to be interpreted differently based on the position of the spatially - aware projector and digital pen in a given space . as a result , paper is no longer just a static source of data , but it is also used as the display surface and a dynamic workspace . virtual ink benefits the user by providing visual feedback without permanently modifying the physical display surface . the spatially - aware projector and digital pen enable a user to interact with the design more efficiently and intuitively . 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 . for example , aspects of the present invention may be implemented in hardware or software or in a combination of hardware and software . one embodiment of the invention may be implemented as a program product for use with a computer system . the program ( s ) of the program product define functions of the embodiments ( including the methods described herein ) and can be contained on a variety of computer - readable storage media . illustrative computer - readable storage media include , but are not limited to : ( i ) non - writable storage media ( e . g ., read - only memory devices within a computer such as cd - rom disks readable by a cd - rom drive , flash memory , rom chips or any type of solid - state non - volatile semiconductor memory ) on which information is permanently stored ; and ( ii ) writable storage media ( e . g ., floppy disks within a diskette drive or hard - disk drive or any type of solid - state random - access semiconductor memory ) on which alterable information is stored . such computer - readable storage media , when carrying computer - readable instructions that direct the functions of the present invention , are embodiments of the present invention . in view of the foregoing , the scope of the present invention is determined by the claims that follow .	6
referring now to the drawing , and in particular to fig1 to 4 , there is illustrated a protective shield assembly of the present invention , generally indicated as 10 , and comprised of semicylindrically - shaped half sections or sleeve members 12 and 14 hingeably mounted to one another by hinge members , generally indicated as 16 . the hinge members are comprised of half hinge elements 18 and 20 mounted , such as by welding , to the respective semicylindrically - shaped half sections or sleeve members 12 and 14 and maintained in hinged relationship by hinge pin 22 . the protective shield assembly 10 is formed with a securing assembly , generally indicated as 24 , and comprised of a looped strap 26 including a buckle 28 , mounted such as by rivets 30 to the member 12 , and by a strap 32 mounted , such as by rivets 34 to the member 14 . proximate the ends of the protective shield assembly 10 and mounted to inner surfaces of the members 12 and 14 , such as by welding , there are provided inwardly - extending arm members 36 . a semicircularly - shaped support member 38 is mounted to paired arm members 36 in a manner to engage the leg of the animal , such as illustrated in fig4 . the semicircularly - shaped support members 38 are preferably formed of a metal or plastic overlayed with a protective outer layer of a resilient material , such as rubber , foamed rubber of the like . the members 12 and 14 may be formed of a metal , such as aluminum or stainless steel , or may be formed of a thermoplastic material , such as polycarbonate or like plastic material having physical properties to withstand the effects of gnawing or chewing by the animal . it will be understood by one skilled in the art that the hinge assemblies 16 , buckle assembly 24 , arm members 26 , etc . are secured to the members 12 and 14 by means compatible with the materials of construction of the members 12 and 14 . additionally , while the semicylindrically - shaped members are illustrated as being formed of a curved surface , the surface may be corrugated or formed of a plurality of planar surfaces . still further , while a universal protective shield assembly would be desirable for any size animal , the protective shield assemblies of the present invention are made in varying lengths and of varying spacial distances between the support member 38 and the members 12 and 16 . in operation , the injury to the animal is first cleaned and treated with an antiseptic material and a normal active treatment protocol performed whereupon the protective shield assembly 10 of the present invention is caused to be encircled about the treated area of the leg of the animal in a manner such that the treated area is positioned between the semicircularly - shaped support members 38 , i . e . out of contact with the treated area to minimize aggravation to the injury wound . the strap 32 is positioned within the buckle 28 and drawn fast to a point whereby the force between the support elements 38 and the leg of the animal is sufficient to maintain the protective shield assembly 10 of the present invention at the desired position but with a support force that is insufficient to cause discomfort to the animal or to aggravate the treatment protocol by reducing circulation to the injury or wound . while the invention has been described in connection with an exemplary embodiment thereof , it will be understood that many modifications will be apparent to those of ordinary skill in the art and that this application is intended to cover any adaptation or variation thereof ; therefore , it is manifestly intended that this invention be only limited by the claims and the equivalent thereof .	0
in various embodiments as illustrated in fig1 - 5 , a distributed system of sensor elements , communication nodes , and a central reporting application server communicate to monitor statistics of electrical conductors . in one embodiment , an electrical conductor is a transformer or a power line ; however , it should be appreciated that an electrical conductor is any suitable electrical device . a sensor element is a device that connects to an electrical conductor to be monitored . a communication node is a device that receives messages and data from the sensor elements , aggregates the data , and relays it to either another communication node , out to a network connection ( e . g , a lan or wan network ), or broadcasts an alert if needed . the central reporting application server receives messages from the communication nodes directly , or through an intermediate network connection ( e . g ., a lan or wan connection ). it should be appreciated that the above elements are not required and / or can be replaced by any suitable element configured for any suitable purpose . referring to fig1 , in one embodiment , a plurality of sensor elements 100 a - 100 c are each connected to an electrical conductor to capture and record at least one statistic of the monitored electrical conductors 105 a - 105 c ( e . g ., peak voltage of the electrical conductors 105 a - 105 c or any other suitable function or operating characteristic of the monitored electrical conductors 105 a - 105 c ). the sensor elements 100 a - 100 c are also configured to communicate with a communication node 110 ; however , it should be appreciated that the sensor element can be configured to communicate with any suitable device . more specifically , the sensor elements 100 a - 100 c are configured to transmit at least one message to the communication node 110 regarding the at least one recorded statistic of the monitored electrical conductors 105 a - 105 c . the communication node 110 is configured to transmit any received messages from the sensor elements 100 a - 100 c to a central reporting application server 120 . in one embodiment , as illustrated in fig2 , sensor element 200 includes a plurality of components . in one embodiment , sensor element 200 includes a processor 210 component for handling computing tasks such as processing captured data of a monitored electrical conductor and writing the captured data to a storage device . the processor 210 can also handle or assist in other processing tasks of the sensor element 200 such as communicating with a communication node . it should be appreciated that the processor can be configured to process any suitable task or assist other sensor element 200 components in completing processing tasks . in one embodiment , sensor element 200 includes data storage 220 for storing collected electrical conductor data for long term and / or short term storage . the data storage 220 can be static ram , dynamic ram , optical storage , or any other suitable storage component . it should be appreciated that sensor element 200 may not include any long term storage and immediately forward any captured statistical data to a communication node . in one embodiment , sensor element 200 includes and energy collection component 230 and an energy storage component 240 . the energy collection component 230 and energy storage component 240 can harvest electrical energy from the electrical conductor being monitored for data collection purposes and to provide at least part or all of the power requirements of the sensor element 200 . alternatively , sensor element 200 can receive electrical power from electrical outlets , solar panels , or from any other suitable source . in one embodiment , sensor element 200 includes an electrical conductor monitoring interface component 250 . the electrical conductor monitoring interface component 250 enables the sensor element to connect to the electrical conductor to measure at least one statistic of the electrical conductor ( e . g ., temperature or peak voltage ). sensor element 200 may also use the electrical conductor monitoring interface component 250 to draw electrical power to provide the power requirements for sensor element 200 . it should be appreciated that electrical conductor monitoring interface component 250 can include any number of suitable components for measuring any desired feature of the connected electrical conductor . it should also be appreciated that electrical conductor monitoring interface component 250 may include a plurality of different components for measuring a plurality of features of the connected electrical conductor simultaneously or asynchronously . in one embodiment , sensor element 200 also includes a communication interface component 260 . the communication interface 260 may include hardware or software to connect to a local wireless network or to a hard wired ethernet connection , enabling communication with a communication node . however , it should be appreciated that the communication interface 260 can be any suitable network interface for connecting to any suitable network . it should also be appreciated that communication interface 260 can also be configured to connect to any suitable device ( e . g ., devices other than a communication node in one embodiment ). in one embodiment , the communication node may comprise an ibm or macintosh compatible personal computer that includes components ( e . g ., a general purpose cpu , data storage , graphics card , os , application programs , etc .) that enable it to function as a general purpose personal computer in addition to performing functions of the communication nodes . however it should be appreciated that the communication node may include any suitable set hardware and software components that are focused on receiving and forwarding sensor element messages to a central reporting application server to minimize the cost of the communication node . in one embodiment the central reporting application server may comprise an ibm or macintosh compatible personal computer , a workstation , a mini - computer , a mainframe , or other types of computers having at least a microprocessor , disk storage and some memory for processing . in one embodiment , the central reporting application server may also comprise a nc ( network computer ) in which there is no disk for storage , or a nc operating in a cloud computing environment where data computation and analysis tasks are distributed and shared over a plurality of computers of the same or different configuration . in one embodiment , when current is flowing through the monitored conductors , the sensor elements each harvest electrical energy , and periodically transmit a short status message to a nearby communication node ( e . g ., a communication node with communication range ). the status message may be as short as an identifier , or it may also include information such as a peak or real - time current reading , conductor temperature , etc . the communication node receives these messages , and relays them to other nodes , relays them back to the receiving central reporting application server through a lan / wan interface , or broadcasts an alert . in one embodiment , a broadcasted alert can be sent directly to a user ( e . g ., a technician ) through email , sms , audio voice alerts sent through the pstn or cellular networks , or through any suitable communications method . alternatively , the communication node may aggregate the status reports , and transmit a single status message or measurement , instead of transmitting each individual message or reading . one process for monitoring electrical conductors is illustrated in fig3 . at step 300 a sensor element monitors a connected electrical conductor and captures at least one statistic of the connected conductor ( e . g ., the conductor &# 39 ; s peak voltage , open circuit conditions , etc .). at step 310 , the sensor element transmits the at least one captured statistic to communication node located with communication range after a predetermined amount of time . at step 320 , the communication node receives the at least one transmitted electrical conductor statistic from the at least one sensor element . at step 330 , the communication node transmits the at least one received electrical conductor statistic to a central reporting application server after a predetermined amount of time . in one embodiment , the communication node may transmit the at least one received electrical conductor statistic to a central reporting application server after collecting a predetermined amount of electrical conductor statistical data . in one embodiment , the sensor elements are self - contained , and powered by the current flowing through the monitored electrical conductor . in this embodiment , the power may be harvested by using a magnetic coupling , or through a rogowski coil and specialized power harvesting circuitry . alternatively , the ambient electric field may be used with capacitive coupling , or with a mechanical harvesting system to utilize the 60 hz vibration of the conductor . a battery or line powered version is also possible , or even an rfid - style system where the communication node broadcasts a burst which powers the sensor element during the sensor read and transmission . a hybrid or mixed approach is also possible . in one embodiment wherein the sensor element is self powered , the sensor element accumulates energy from the monitored electrical conductor . when enough energy for a transmission has been gathered ( or the periodic transmit time has occurred ), the element broadcasts a short status message to all available communication nodes in range . this broadcast can be a low power rf or vlf burst , but can also be another communication means , such as power line carrier , infrared , sonic , or any other suitable device or method . in one embodiment , the status message can minimally contain enough information for the communication node to determine that the monitored conductor has not failed ( e . g . just the sensor unique identifier , either a globally unique identifier , or unique within range of the communication node ); however , the status message is not required to include such minimal information and can include any suitable information . if the sensor element is powered by drawing power from the current through the conductor , then the reception of the signal itself is an indication that the conductor is still functioning . additionally , the sensor element may harvest enough energy to actually measure the electrical current through the conductor , or may be able to estimate this current based on the energy level harvested , or the time required to harvest a certain amount of energy . this information may also be sent to the communication node , or the communication node may be able to estimate this based on a received signal power level , a time between message bursts , or other signal characteristics which may be correlated ( intentionally or as a side - effect of the sensor element operation and construction ) with the electrical conductor current . in various embodiments , the minimum energy harvest time or the received signal strength is highly correlated with the monitored current , and can be used to estimate the conductor current . the conversion to actual amperes of current may occur later , based on after - the - fact conversion factors , or may be used to indicate changes in current , rather than absolute current levels ( e . g . to indicate increased conductor loading over a period of time ). in one embodiment wherein the sensor element is self - powered , a failure to receive a sensor element status message in a predetermined amount of time indicates a likely monitored conductor failure , and would generate an alarm condition . additionally , in one embodiment , either the communication node or the central reporting application server can track the periods of time between receipt of the sensor element status message . in one embodiment , a single sensor element can be configured to monitor multiple electrical conductors . in one such embodiment , any one or more of the electrical conductors may provide power for the element , but each individual electrical conductor is monitored for current flow or any other desired statistic as discussed above . in one embodiment , to increase redundancy and reliability , multiple sensor elements may be used to monitor the same electrical conductor . in one such embodiment , the communication node may be programmed to declare an alert if all sensors on the same conductor indicate a conductor failure ; however , the communication node can be programmed in any suitable manner . in another such embodiment , a first sensor element can be configured to monitor a first electrical conductor ; however , the first sensor element can be connected to a second electrical conductor to serve as a backup sensor element for the second electrical conductor . if a second sensor element monitoring the second electrical conductor malfunctioned or failed , the first sensor element can be configured to monitor both the first electrical conductor and the second electrical conductor . in one such embodiment , a sensor element can be configured to serve as a backup monitor for any suitable number of electrical conductors . the sensor element broadcast times are timed to optimally reduce interference from each other in various embodiments . in one embodiment wherein the sensor element is self - powered , the energy harvest time can factors into the broadcast timing , since enough energy must be harvested to transmit a message . however , it should be appreciated that the sensor element can be configured to communicate with communication nodes and / or the central reporting application server using any suitable communication protocol . thus , in some embodiments , a communication protocol can eliminate or reduce the need to configure the timing of the sensor elements broadcasts . in one embodiment , the communication node contains suitable circuitry and hardware components to send and receive messages from one or more types of sensor elements . these messages may be sent directly through a network or other concentrator device , where they eventually end up at the central reporting application server . alternatively , the communication node may rebroadcast received messages and electrical conductor statistics data to other nearby communication nodes ( e . g . communication nodes within range of bluetooth , wifi , a direct ethernet connection , or any other known short range communication protocols ), distant communication nodes ( e . g ., communication nodes beyond the range of bluetooth / wifi / ethernet that may require longer range communication protocols such as wimax , ppp , atm , fddi , various cellular standards , or any other suitable long range communication protocols ), or broadcast using low - power fm / am broadcast bands or other suitable communication protocols directly to users . in one embodiment where the communication node includes features of a general purpose personal computer , the communication node can be configured for tasks beyond aggregating data and routing the data to the central reporting application server . in one such embodiment , the communication node can be configured to aggregate electrical conductor statistics received from one or more sensor elements and analyze the data for more specific reporting purposes . for example the communication node can be configured to generate a report that the average temperature over a period of time is greater than the tolerances of the electrical conductor which requires the electrical conductor to be replaced because failure is imminent due to the environment conditions . thus , in one such embodiment , reporting and analysis of the electrical conductor data can be shared with central reporting application server . it should be also appreciated that the communication node can also be configured to directly send alerts to end users ( e . g ., technicians ) detailing the communication node &# 39 ; s analysis of the electrical conductor data . in one such embodiment , the communication node can be configured to communicate with end users through a pstn , sms , cellular links , email , or any other suitable communication channel . in one embodiment as illustrated in fig4 , the monitoring system is deployed in an underground network grid . in one such embodiment , a vault such as vault 400 a or vault 400 b is positioned underground at least at every city block . each vault 400 a and 400 b includes a plurality of sensor elements 405 a - 405 f , wherein each sensor element 405 a - 405 f is connect to at least one electrical conductor ( not shown ). in one embodiment , due to the self - contained nature of the sensor elements 405 a - 405 c located in vault 400 a , sensor elements 405 a - 405 c do not require wiring for communicating with communication node 410 a , which is a significant advantage over other methods due to shorter installation times and reduced material costs . in one embodiment , each vault can be configured with wireless communication between sensor elements and the communication node . however , as illustrated in vault 400 b , sensor elements 405 d - 405 f can be hard wired to communication node 410 b for communication purposes . thus , it should be appreciated different vaults can be configured with different communication methods as is deemed appropriate based on costs and engineering requirements . furthermore , in one embodiment , each vault can be configured with at least one communication node ; however any suitable number of communication nodes can be present in a vault . in one embodiment , within the vault , sensor elements 405 a - 405 c and 405 d - 405 f send messages to the communication nodes 400 a and 400 b respectively . the communication nodes 400 a and 400 b relay the messages upstream to a central reporting software application server 430 . the relay communications method may be powerline carrier based ( e . g . hazeltine , turtle , opera , homeplug , insteon , etc . ), rf ( e . g . bluetooth , wifi , etc . back to a lan ), or any other suitable method . in one embodiment , additional reporting software application servers may be incorporated into the system depending on the number of vaults being monitored . thus , different vaults may be configured to send messages to different central reporting application servers . in one embodiment as illustrated in fig5 , communication nodes can be connected to other communication nodes to form a mesh network . in one embodiment , a communication node may monitor different numbers of sensor elements at different monitored sites . in one such example as illustrated in fig5 , communication node 510 a receives messages from sensor elements 500 a - 500 c ; communication node 510 b receives messages from sensor elements 500 d and 500 e ; communication node 510 c receives messages from sensor element 500 f ; and communication node 510 d receives messages from sensor elements 500 g - 500 j . in this embodiment , communication node 510 a is connected to the central reporting application server 520 and to communication node 510 d ; communication node 510 b is connected to central reporting application server 520 and to communication node 510 c ; communication node 510 c is connected to communication node 510 b and communication node 510 d ; and communication node 510 d is connected to communication node 510 c , communication node 510 a , and to central reporting application server 520 . in this example configuration , communication nodes 510 a - 510 d can be configured to transmit the received messages ( or aggregated messages ) to other nearby communication nodes that are then relayed to the central reporting application server 520 forming a mesh network ( e . g ., any one or more of the communication nodes 510 a - 510 d can serve as a message aggregator that communicates directly with the central reporting application server 520 ). in one example of the mesh network , if the link between communication node 510 a and central reporting application server 520 becomes unusable , communication node 510 a can route messages through communication 510 d to central reporting application server 520 . in one embodiment , the underground vault communication nodes ( as described in connection with fig4 ) can also be configured to form a mesh network . in one embodiment , certain vaults also optionally contain more advanced communication nodes , or other communication / data concentrators , that relay messages out of the mesh and onto a lan / wan for transmission back to the central reporting application server . optionally , programming / configuration data for any of the communication nodes 510 a - 510 d and / or the sensor elements 500 a - 500 j may be sent through the mesh network to change at least one device parameter , programming setup , silence alarms , etc . it should also be appreciated that each communication node 510 could be connected to the central reporting application server 520 and each communication node 510 could be connected to one or more communication nodes , or not connected to any communication nodes . sensor element and communication node parameters may be programmable in various embodiments . for example , the sensor element status message contents , energy harvesting / collection parameters , etc . may be software or hardware selectable . the communication node relay and aggregation logic , etc . may also be programmable . additionally , the communication node may log all received sensor element transmissions , especially if they contain measurement data such as current level , or log date / time stamps of alert conditions ( e . g . failure of sensor element to broadcast , which indicates that a monitored conductor failed ). the recording parameters may also be set in the communication node . the communication nodes may be programmed with information about the sensor elements within range ( e . g . in the same vault ), or preferably , it may automatically add sensor elements . in the latter case , when the communication node receives messages from a sensor element , it automatically adds the transmitting sensor element to an internal list of monitored sensor elements . thus , once the sensor element is added to the list of monitored sensor elements , if the communication node fails to receive a timely status message from the sensor element , an alert condition is triggered . alternatively , the communication nodes may not relay messages / data to other communication nodes . in one such embodiment , the communication nodes are normally silent , and only broadcast a message if a conductor has failed ( typically indicated by the failure of a sensor element to send a message within a specified amount of time ), or a limit has been reached . this broadcast may be through a low power radio transmitter , or indicated by some other suitable alert or annunciator mechanism ( e . g . visible strobe light , etc .). if low - power fm / am broadcast bands are used , users may use a standard broadcast fm / am radio receiver or other suitable receiver for “ drive - by ” reception of vault communication node prerecorded or constructed voice messages . in various such embodiments , there may not be a central software system . status data may be automatically recorded during the drive - by a suitable receiver system , and transmitted to the central software when back in the office , or relayed immediately by an in - vehicle system such as cell phone or other wan connection . a combination of communication node types may be used , or a single node may incorporate more than one of these methods . it should be understood that various changes and modifications to the presently preferred embodiments described herein will be apparent to those skilled in the art . such changes and modifications can be made without departing from the spirit and scope of the present subject matter and without diminishing its intended advantages . it is therefore intended that such changes and modifications be covered by the appended claims .	8
the process according to the invention and certain aspects of its industrial application are described in the following examples . however , the process according to the invention is by no means restricted to these examples . thus , the strains according to the invention can be cultured on low - cost media , in particular using as carbon - containing culture substrate hexadecanes or gas oils ( which enables paraffin to be extracted from gas oils ) or even using lactoserum as the complete medium . these examples illustrating the application of the process according to the invention were all carried out with the strain r 312 lodged in the collection de la chaire de genetique de l &# 39 ; ecole nationale superieure agronomique de montpellier , and also at the centraal bureau voor schimmelcultures ( holland ) under the number cbs 717 - 73 . these examples are particularly intended to illustrate the non - specificity of the strains selected , and it is for this reason that they were all carried out with the strain r 312 , although almost all the strains selected are capable of the hydrolyses described hereinafter . the strain r 312 is cultured on a medium containing glucose as carbon source . after culture , the cells are centrifuged , washed with a physiological salt solution and then suspended in the reaction medium consisting of a 10 % by weight solution of lactonitrile obtained by chemical synthesis . the ph - value is adjusted to 8 with potash or ammonia . the bacterial cells , representing approximately 20 to 40 g of dry material per liter , completely hydrolyzed the nitrile over a period of 2 to 3 hours with stirring at a temperature of 25 ° c . they are then eliminated by centrifuging . the supernatant liquid contains ammonium lactate which can be recovered in a quantitative yield by drying . this product may be used as such , because its applications are numerous , for example as an antiscaling agent in washing solutions . the lactic acid can also be recovered in a quantitative yield by methods known per se . for example , acidification may be followed by continuous extraction with ethyl ether or with any other suitable organic solvent . the lactic acid thus recovered is suitable for use , for example in the food industry and in the chemical or pharmaceutical industry . in this process , lactonitrile is synthesised in situ by the action of an aqueous acetaldehyde solution on an aqueous solution of hydrocyanic acid in exactly the same molar concentrations as above . the ph - value of the solution is adjusted to approximately 5 by the addition of concentrated ammonia in order to start the reaction . in a second stage , the ph - value of the solution is adjusted to 8 by the addition of ammonia , the bacterial cells are suspended in the medium in a quantity of 20 to 40 g of dry material per liter , and hydrolysis carried out over a period of 2 to 3 hours in the manner described in the preceding example . as in the preceding examples , the strain r 312 is cultured on a medium containing glucose as carbon source . after culture , the cells are centrifuged , washed with a physiological salt solution and then suspended in the reaction medium which is a 6 % aqueous solution of glycinonitrile ( in hydrochloride form ). the ph - value of the solution is adjusted to approximately 8 by adding potash or ammonia . the bacterial cells , representing from 60 to 80 g of dry material per liter , completely convert the nitrile into acid over a period of about 5 hours at a temperature of 25 ° c . the ph - value is kept at about 8 for the first hour and at ph 7 for the next 4 hours . the cells are then eliminated by centrifuging . glycine is then precipitated from the solution obtained by reducing the solution to 1 / 5th of its volume and by adding methanol in the absence of heat . the strain r 312 is cultured on a medium containing glucose as carbon source . after culture , the cells are centrifuged , washed with a physiological salt solution and then suspended in a reaction medium consisting of a 5 % by weight aqueous solution of α - aminopropionitrile hydrochloride . the ph - value is adjusted to 8 and kept at that level for 2 hours . the bacterial cells , representing 20 to 40 g of dry material per liter , completely hydrolyze the solution over a period of 2 to 3 hours with stirring at a temperature of 25 ° c . after the cells have been eliminated by centrifuging , the solution contains approximately 40 g of α - alanine per liter which is recovered by known techniques . the strain r 312 is cultured and recovered in the same way as described above . it is suspended in a reaction medium consisting of a 5 % by weight aqueous solution of amino - 3 - propionitrile . the ph - value is adjusted to 8 and is kept at that level for 30 minutes . the ph - value is then reduced to 7 and kept at that value for 5 hours with stirring at a temperature of 25 ° c . the bacterial cells , representing 60 to 80 g of dry material per liter , completely hydrolyze the solution under these conditions . after the cells have been eliminated by centrifuging , the solution contains approximately 60 g per liter of β - alanine which is recovered by known techniques . the strain r 312 is cultured and recovered in the same was as described above . it is suspended in a reaction medium consisting of a 6 % by weight solution in water of α - amino - γ - methyl thiobutyronitrile sulphate . the ph - value is adjusted to 8 . the bacterial cells , representing 20 to 40 g of dry material per liter , completely hydrolyze the solution after 3 hours with stirring at a temperature of 25 ° c . after the cells had been eliminated by centrifuging , the solution is reduced to 1 / 3rd of its volume and adjusted to ph 7 . the methionine precipitates . the yield is of the order of 80 %. as in example 2 , α - amino - γ - methyl thiobutyronitrile can be prepared in situ from methylmercapto propion aldehyde , ammonia and alkali cyanide used in stoichiometric proportions . on completion of the reaction , the bacteria are suspended . the further procedure is then as in example 6 . some remarks should be made on the reaction equilibria prevailing in view of the toxicity of the cyanides . in cases where hydrolyzed nitrile participates in an equilibrium with hydrocyanic acid : on the one hand , the constants measured are very favorable to the nitrile in every case . on the other hand , the hydrolysis reaction displaces the equilibrium towards the disappearance and complete utilisation of the cyanide present in the medium . nevertheless , the concentration of cyanide in the starting products has to be finally checked in order to avoid any accidents ( unfavorable stoichiometric proportions at the outset always being possible ). accordingly , it is possible by this process to hydrolyzed a large number of nitriles under mild conditions from a simple reaction medium , and to obtain extremely pure compounds in substantially quantitative yields .	8
the novel administration and treatment means of the invention results from knowledge of a parasitic nematode , the ascaris roundworm life cycle in human beings , as detailed below . ascaris lumbricoides is one of the largest and most common parasites found in humans . the adult females of this species can measure up to 18 inches long ( males are generally shorter ), and it is estimated that 25 % of the world &# 39 ; s population is infected with this nematode . the adult worms live in the small intestine and eggs are passed in the faeces . a single female can produce up to 200 , 000 eggs each day . about two weeks after passage in the faeces the eggs contain an infective larval or juvenile stage , and humans are infected when they ingest such infective eggs . the eggs hatch in the small intestine , the juvenile penetrates the small intestine and enters the circulatory system , and quickly the juvenile worm makes its way to the capillaries of the lungs . in the lung capillaries the juvenile worm secrets proteolytic enzymes from its mouth . these enzymes act upon the cells of the capillary wall . the wall ultimately breaks down and the worm is able to move across the blood - air barrier into the lung . the juvenile worm then migrates up the air passages into the pharynx where it is swallowed , and once in the small intestine the juvenile grows into an adult worm . examples of specific worm proteases include the strongyloides stercoralis — the larvae of this nematode parasite can move through tissue at speeds of up to 10 cm per hour . this nematode larvae secrete a potent histolytic metalloprotease to facilitate the rapid migration . this protease has elastase activity and catalyses the degradation of a model of dermal extracellular matrix . ascaris suum , in the tissue - invasive infective and lung stage larvae release proteinases . specifically , this activity contained multiple proteolytic enzyme activities , particularly chymotryptic , tryptic collagenolylic and elastolytic activities . the novel administration means of the invention employs the method of blood - air barrier movement exhibited by the worm . the active agent , which in the examples considered here , is useful in treatment of cystic fibrosis , is brought into the vicinity of the lung capillary and , with the excretion or otherwise application of proteases , is able to cross the boundary into the lung . it will be appreciated by one skilled in the art that although this discussion is primarily concerned with cystic fibrosis the novel administration method of the invention may well be used to treat other lung conditions as it allows a cell or a treatment species access to the lung . in the case of cystic fibrosis the “ treatment species ” is one or more cells having normal cftr production . in other applications the treatment species may be other drugs ( anticancer , asthma drugs etc ) or other chemical or biological bio - actives for which will have some effect in the lung . an essential process in the invention is access of the treatment species into the lung via access to the lung epithelia . the result could be incorporation of the treatment species ( or a derivative ) into the epithelial layer as is the case with cftr functioning cells . alternatively access to the lung epithelia of the treatment species could result in access through the epithelia by disruption or otherwise , of the treatment species into the lung itself . the “ active agent ” contemplated here is cellular material from a suitable mammal donor . more specifically it may take one of ( but is not restricted to ) three forms : i ) human cells in which the cftr protein is present ( in other words , the chloride pump is functioning ); ii ) porcine cells in which the cftr protein is present ; iii ) human stem cells . the cells are administered in the form of a biological delivery device . this is more specifically encapsulated cells , or encapsulated cell clusters . the following outlines our preferred methodology for creation of the device but it will be appreciated other known variations or alternatives for this methodology may also be included without departing from the scope of the invention . cells taken from healthy humans ( not having cystic fibrosis ) cells taken from other suitable mammalian species ( such as pigs ) cells taken from transgenic species not having the defective gene . human stem cells . in our preferred method we prepare clusters of cells which will then be encapsulated . as the size of the overall device is crucial in the method of the invention ( ultimately a device in range 20 - 80 micrometers is desired ) then a cluster of & lt ; 70 micrometers is ( pre - encapsulation ) required to provide this size . we have prepared micro clusters of porcine lung epithelia according to the following method . i . dissection of parenchyma from large vessels and airways of the donor species ii . removal of red blood cells iii . digestion with liberase or similar iv . addition of nutrient media ( including rpmi , nicotinamide , human serum albumin , pig serum , aproxin ) v . removal of gross clumps by filtration vi . segmentation and resuspension in the nutrient medium vii . culture in non - adherent culture dishes ( up to one month ) an example lung cluster prepared by such a method is shown in fig1 . the image is a uv / phase contrast the spheroid being some 60 micrometers in diameter . fig2 illustrates a number of such clusters . our cell transplant work has shown that transplanted cells even from foreign species can be protected from rejection after transplantation without the need to use severe immune suppressing drugs . this is done by coating the cells or clusters of such cells with ‘ micro - capsules ’, which allow the required cell secretion out , and nutrients in but excludes the larger components of the immune system . smaller components can be neutralised by use of nicotinamide - a harmless vitamin derivative . one particular encapsulation process ( as an example ) follows . it employs alginate as an encapsulation material but equally other in vivo similarly behaving materials may be employed . take a population of cells ( or cell clusters ) to be transplanted encapsulate or encase in an alginate coating apply polyornithine coat once more in alginate the proteolytic enzyme may be inserted on top of the polyornithine before application of the second coating of alginate . alternatively it may be mixed with the final alginate coating in the form , for example as gelatin ( or other suitable ) microcapsules . the outermost alginate coating will dissolve relatively quickly in blood of the patient ( for example within 2 days ) to expose the proteolytic enzyme . with particular reference to fig3 , a form of preferred device of the invention is illustrated . in particular we have shown preparation of triple - layered encapsulation lung epithelial structures , as organotypic structures with beaded protease clusters . ( a ) porcine lung epithelia are prepared in modified cell culture media as spheroidal organotypic structures , the spheroid having an outer layer of epithelial cells a lumen filled with liquid . ( b ) a first layer of alginate outside the cells is deposited by calcium gelation . ( c ) the outer surface of the alginate is stabilised with a layer of poly - l - ornithine . preferably the beaded clusters of proteases are deposited with the poly - l - ornithine layer . ( d ) there is an option for a third layer of alginate to cover the protease beads in order to conserve their activity . the delivery mode takes advantage of the circulation system , in particular the venous system . the delivery device is injected into a vein and then moves through the system until it reaches the smaller diameter capillaries of the lungs . as a result of the decreasing capillary size the device will eventually get “ jammed ” or impact in the vessel in the lung . the impaction may also cause compaction of the device . the size of the device is crucial to the working of the invention . it must be large enough to impact in the capillary system within the lung but small enough not to lodge earlier in the venous system . lung capillaries are approximately 7 - 13μ diameter . this lung microvasulative has a diameter less than 100μ . once the device is impacted , via the structure of the outer wall of the device is destabilised and the proteases released such that they come into contact with the capillary wall . the capillary wall will then breakdown admitting the ( residue of ) the device , and specifically the treatment cells . the treatment cells then , come into contact with the epithelial cells inside the lung surface . as has been known in the prior art the similar properties of the treatment cells allow merging of the treatment cells with the epithelial cells to form micro chimaeric clusters within the lung ( a mixture of the two cells types ). ultimately , the human capillary wall reorganises itself whilst the epithelial cells now include treatment cells with a healthy chloride pump activity on the lung wall . with particular reference to fig4 we have illustrated an example of impaction of encapsulated lung structures through blood - air barrier and integration into the patient &# 39 ; s airway structure . in stage one the capsules are injected into a suitable vein , travel in the venous blood to the lung where the narrow capillaries prevent onward movement and the structure is impacted and compressed and the capsule structure compromised . in stage two the outer surface of the capsule structure is sufficiently compromised to release the protease beads that degrade the capillary wall and the basal layer of the airway epithelium , releasing epithelial cells in a focal area in stage three the encapsulated cells are released from the capillary into the epithelial layer where they integrate as a micro - chimaeric group of cells capable of expressing cftr and promoting chloride transport and water secretion . the assimilated cells should start to cause water transport into the lung linings via the chloride pumping system . cystic fibrosis studies have shown you only need & lt ; 1 % of total chloride pumping ability to significantly decrease cystic fibrosis symptoms . administration is via the venous system thus the administered devices may proceed via the capillary system to all areas of the lung . this is an advantage over prior art treatment methods which generally only allow treatment in one specific area . where in the foregoing description reference has been made to elements or integers having known equivalents , then such equivalents are included as if they were individually set forth . although the invention has been described by way of example and with reference to particular embodiments , it is to be understood that modifications and / or improvements may be made without departing from the scope or spirit of the invention .	0
persons of ordinary skill in the art will realize that the following description of the present invention is illustrative only and not in any way limiting . other embodiments of the invention will readily suggest themselves to such skilled persons . fig6 shows an embodiment of an inverting flip - flop of the present invention . a function generator circuit is coupled to the data input of the flip - flop via a programmable routing element . the inverting flip - flop includes an inverting multiplexer ( a multiplexer with one of its inputs logically inverted ) in series with its data input signal . the inverting multiplexer causes the output signal from the flip - flop to have the opposite logical polarity from the data input signal . the inverting multiplexer also buffers the data input signal , providing a faster data input signal path than non - inverting flip - flops of the prior art . present in fig6 are function generator 10 , flip - flop 12 , and multiplexers 14 , 16 , 18 , 20 , 22 , 24 , 26 and 30 previously discussed . also present in fig6 is inverting multiplexer 58 which replaces multiplexer 28 of fig4 and complex flip - flop 60 which replaces complex flip - flop 32 of fig4 . the output y of the logic module 10 and the output q of the flip - flop 60 are coupled to programmable routing elements not shown in the drawing figure . inverting multiplexer 58 is shown having an inversion on its data input that is coupled to the output of multiplexer 26 . this indicates a logical inversion in the signal path . correspondingly the input to the data input of complex flip - flop 60 is labeled db in the diagram . fig7 shows exemplary circuit details of complex flip - flop 60 . present in fig7 is flip - flop 12 comprising transmission gates 40 , 46 , 50 and 56 and inverters 42 , 44 , 48 , 52 and 54 previously discussed . also present in fig7 is inverting multiplexer 58 comprising tri - state inverter 62 , transmission gate 64 , and inverter 66 . tri - state inverter 62 has a data input coupled to the db input of complex flip - flop 60 , a non - inverting enable input coupled to the en input of complex flip - flop 60 , an inverting enable input coupled to the output of inverter 66 ( labeled enb in the figure ), and an output coupled to the output of transmission gate 64 and the input of transmission gate 40 ( labeled di in the figure ). transmission gate 64 has a data input coupled to the output of inverter 52 , the input of inverter 54 , and the output of complex flip - flop 60 ( labeled q in the figure ), an inverting enable input coupled to the en input of complex flip - flop 60 , a non - inverting enable input ( labeled enb in the figure ) coupled to the output of inverter 66 , and an output coupled to the input of transmission gate 40 ( labeled di in the figure ) and the output of tri - state inverter 62 . inverter 66 has an input coupled to the en input of complex flip - flop 60 and an output coupled to the internal enb signal . when the en signal is at logic - 0 , inverter 66 drives the enb signal to logic - 1 . this causes tri - state inverter 62 to present high - impedance to node di and causes transmission gate 64 to be open presenting the logic value on the node q to the node di . this corresponds to complex flip - flop 60 being disabled . when the en signal is at logic - 1 , inverter 66 drives the enb signal to logic - 0 . this causes tri - state inverter 62 to drive the complement of the logic value on the node db to node di and causes transmission gate 64 to be closed presenting high impedance to the node di . this corresponds to complex flip - flop 60 being enabled . the presence of tri - state inverter 62 breaks the long chain of pass transistors and transmission gates that can create a substantial amount of rc delay discussed in conjunction with fig5 . tri - state inverter 62 acts as a buffer while only costing the delay of a single gain stage instead of the two gain stages required by a non - inverting buffer . this increases the speed of signal propagation through multiplexers 20 , 26 and 58 and into flip - flop 12 in fig6 relative to the analogous path through multiplexers 20 , 26 and 28 and flip - flop 12 in fig4 . however , tri - state inverter 62 inverts the logical polarity of the complex flip - flop 60 which requires that the design software for an fpga implementing such a circuit have the ability to compensate for the logic inversions that it introduces . persons skilled in the art will realize that many different flip - flop circuits are known in the art and will understand that the choice of the exemplary circuits shown in fig7 is in no way limiting . fig8 a shows , as indicated generally by reference number 62 - a , a first exemplary implementation of the tri - state inverter 62 of fig7 . circuit 62 - a comprises pmos transistors 68 and 70 and nmos transistors 72 and 74 . pmos transistor 68 has a source node coupled to vcc , a gate node coupled to the enb signal , and a drain node coupled to the source node of pmos transistor 70 . pmos transistor 70 has a source node coupled to the drain node of pmos transistor 68 , a gate node coupled to the gate node of nmos transistor 72 and the input node db , and a drain node coupled to the drain node of nmos transistor 72 and the output node di . nmos transistor 72 has a source node coupled to the drain node of nmos transistor 74 , a gate node coupled to the gate node of pmos transistor 70 and the input node db , and a drain node coupled to the drain node of pmos transistor 70 and the output node di . nmos transistor 74 has a source node coupled to ground , a gate node coupled to the en signal , and a drain node coupled to the source node of nmos transistor 72 . when en is at logic - 1 and enb is at logic - 0 , the transistors 68 and 74 are both on and the transistors 70 and 72 act as a cmos inverter passing the logical complement of the signal on db to the node di . when en is at logic - 0 and enb is at logic - 1 , the transistors 68 and 74 are both off and high impedance is presented to the node di . fig8 b shows , as indicated generally by reference number 62 - b , a second exemplary implementation of the tri - state inverter 62 of fig7 . circuit 62 - b comprises inverter 76 and transmission gate 78 . the input of inverter 76 has an input node that is coupled to the db signal and an output node that is coupled to the input of transmission gate 78 . transmission gate 78 has a input node coupled to the output of inverter 76 , a non - inverting enable input coupled to the en signal , an inverting enable input coupled to the enb signal , and an output node coupled to the di signal . when en is at logic - 1 and enb is at logic - 0 , transmission gate 78 is open and passes the logical complement of the signal on db at the output of inverter 76 to the node di . when en is at logic - 0 and enb is at logic - 1 , transmission gate 78 is closed and high impedance is presented to the node di . persons of ordinary skill in the art will realize there are other ways to implement tri - state inverter 62 and the examples chosen in fig8 a and fig8 b are exemplary only and in no way limiting . since the use of inverting fpga flip - flops is unknown in the prior art , it is required that the design software for an fpga implementing such a circuit be adapted to have the ability to compensate for the logic inversions that it introduces . one possible solution would be to let users design using the inverting flip - flop . unfortunately , virtually all fpga designers ( and logic designers in general ) think in terms of non - inverting flip - flops , and trying to force customers to think in an unfamiliar manner is commercially unwise . a more practical approach is to hide the use of the inverting flip - flops inside the design software and then compensate for the logic inversion in the flip - flops while post - processing the end user design . fig9 a shows an illustrative portion of a typical end user logic design to be implemented in an fpga . logic module 80 is shown implementing boolean function a with its output coupled to an input on logic module 82 . logic module 82 is shown implementing boolean function b with its output coupled to the data input of a standard non - inverting flip - flop 84 . flip - flop 84 has a data output coupled to an input on logic module 86 shown implementing boolean function c . fig9 b shows the transformation of the logic design of fig9 a into a logically identical representation . logic modules 80 , 82 and 86 are still present and still implementing boolean functions a , b and c respectively . inverting flip - flop 88 is shown replacing non - inverting flip - flop 84 . the input inversion ( like that of complex flip - flop 60 of fig6 and fig7 ) is indicated by inversion bubble 90 . in order to keep the logic identical , a compensating inversion bubble 92 is shown on the output of logic module 82 . the logical representation of fig9 b is an abstraction created in the design software to realize the end user design in physically available programmable elements . unless , for example , logic module 82 has an inverting output that the interconnect between logic module 82 and inverting flip - flop 88 can be rerouted to , further transformation of the representation of fig9 b is required . fig9 c shows the transformation of the representation of fig9 b into a form that can be physically realized in an fpga . logic modules 80 , 82 and 86 and inverting flip - flop 88 with its inverting data input 90 are still present . however , the boolean function implemented in logic module 82 is now ˜ b which is the logical complement of the original boolean function b . in an fpga which uses look - up tables for function generators this is a very simple transformation . in some fpgas , where different sorts of function generators are used , the transformation can be more complicated if the function ˜ b is not available from logic module 82 . in such cases , the entire logic function implemented by logic modules 80 , 82 and any other logic modules and flip - flops ( not shown ) can be transformed into a boolean equivalent function of a different topology . when designing an fpga with an inverting flip - flop , it is highly desirable to incorporate function generators that work conveniently with the sorts of transformations necessary in the design software used for programming it . fig1 a shows another illustrative portion of a typical end user design . logic module 94 is shown implementing boolean function d with its output coupled to an input on logic module 96 . logic module 96 is shown implementing boolean function e with its output coupled to the data input of a standard non - inverting flip - flop 98 . flip - flop 98 has a data output coupled to an input on logic module 100 shown implementing boolean function g . fig1 b shows the transformation of the logic design of fig1 a into a logically identical representation . logic modules 94 , 96 and 100 are still present and still implementing boolean functions d , e and g respectively . inverting flip - flop 104 is shown replacing non - inverting flip - flop 98 . the input inversion ( like that of complex flip - flop 60 of fig6 and fig7 ) is indicated by inversion bubble 106 . in order to keep the logic identical , a compensating inversion bubble 108 is shown on the output of inverting flip - flop 104 . the logical representation of fig1 b is an abstraction created in the design software to realize the end user design in physically available programmable elements . unless , for example , flip - flop 104 has an inverting output that the interconnect between flip - flop 104 and logic module 100 can be rerouted to , further transformation of the representation of fig1 b is required . fig1 c shows the transformation of the representation of fig1 b into a second logically identical representation . logic modules 94 , 96 and 100 are still present and still implementing boolean functions d , e and g respectively . inverting flip - flop 104 is shown replacing non - inverting flip - flop 98 . the input inversion ( like that of complex flip - flop 60 of fig6 and fig7 ) is indicated by inversion bubble 106 . in order to keep the logic identical , a compensating inversion bubble 110 is shown on the input of logic module 100 replacing the compensating inversion bubble 108 . the logical representation of fig1 c is also an abstraction created in the design software as a means towards realizing the end user design in physically available programmable elements . unless , for example , logic module 100 has an inverting input that the interconnect between flip - flop 104 and logic module 100 can be rerouted to , further transformation of the representation of fig1 c is required . fig1 d shows the transformation of the representation of fig1 c into a form that can be physically realized in an fpga . logic modules 94 , 96 and 100 and inverting flip - flop 104 with its inverting data input 106 are still present . however , the boolean function implemented in logic module 100 is now g ′ which is the logical equivalent of the original boolean function g with an inversion on the input coupled to inverting flip - flop 104 . in an fpga which uses look - up tables for function generators this is a very simple transformation . persons of ordinary skill in the art will appreciate that the examples shown in fig9 a through fig1 d are exemplary and in no way limiting . when transforming boolean functions many different approaches can be taken and other such transformations will readily suggest themselves to such skilled persons . some fpgas have probe circuits which can be used by the end user to monitor logic signals internal to the fpga , primarily for debugging a design . such a scheme is shown in fig1 . shown in fig1 are function generator 10 , complex flip - flop 60 , and multiplexers 14 , 16 , 18 , 20 , 22 , 24 , 26 and 30 previously discussed . the probe circuit comprises nmos transistors 112 and 114 , sense amplifier 116 , probe control circuit 118 , xnor gate 120 , output buffer 122 , and bond pad 124 . nmos transistors 112 and 114 are used to sense the output node q of complex flip - flop 60 . since the gate of nmos transistor 112 is coupled to q , it will be either turned on when q is at logic - 1 or turned off when q is at logic - 0 . signal pen ( for probe enable ) is coupled to the gate of nmos transistor 14 providing the means to enable or disable the probe circuit . nmos transistors 112 and 114 are local to the flip - flop 60 while all other circuits are shared amongst many different flip - flops . sense amplifier 116 is coupled to the drain of nmos transistor 114 . it may be directly coupled to a sense amp at the top of a column of flip - flops , or there may be multiplexing transistors ( not shown ) present to allow sharing the sense amp 116 with many different columns . xnor - gate 120 has a first input coupled to the output of sense amplifier 116 , a second input coupled to an output of probe control circuit 118 , and an output coupled to the input of output buffer 122 . output buffer 122 has an output coupled to bond pad 124 for driving signals off of the fpga integrated circuit device . when the probe circuit is enabled , sense amplifier 116 will amplify the current supplied ( or not supplied ) by nmos transistors 112 and 114 . xnor - gate 120 is used to control the polarity of the signal being sent off chip by output buffer 122 through bond pad 124 . probe control circuit 118 is coupled to a computer running the design software ( through another off - chip connection not shown ) that controls which flip - flop is being probed . since the design software has the programming data available to it , it knows if the polarity of the output signal q of the flip - flop being probed is inverted or not due to the transformations needed to compensate for the use of inverting flip - flops . when using a probe for debugging purposes , the signal stored in a register is a very common thing for the end user to examine . if the flip - flop does not have the expected logic polarity at its output inverted , this can create a very confusing situation for the end user . the most expedient approach is to cancel out the inversions before they leave the fpga at bond pad 124 . in a presently preferred embodiment , all the flip - flop logic modules in the fpga have probe circuits ( though this is not true in all embodiments ). thus the flip - flop 60 is representative of all the flip - flop logic modules in the fpga including flip - flops 84 and 88 in fig9 a through 9c and flip - flops 98 and 104 in fig1 a through 10d . in the example of fig9 a , 9 b and 9 c , the logic sense of the flip - flop 88 is exactly the same as the output of the original flip - flop 84 and no inversion in xnor - gate 120 is needed for probing . however , in the example of fig1 a , 10 b , 10 c and 10 d , the output of the flip - flop 104 is inverted relative to flip - flop 98 and needs to be inverted again in xnor - gate 120 to restore the correct polarity for probing . persons skilled in the art will realize that there are many different ways to build a probe system for an fpga , and that the choice of the circuit presented in fig1 is exemplary only and in no way limiting . while embodiments and applications of this invention have been shown and described , it would be apparent to those skilled in the art that many more modifications than mentioned above are possible without departing from the inventive concepts herein . the invention , therefore , is not to be restricted except in the spirit of the appended claims .	7
the present invention will now be described more fully hereinafter with reference to the accompanying drawings , in which preferred embodiments of the invention are shown . 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 pertains . although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention , suitable methods and materials are described below . any publications , patent applications , patents , or other references mentioned herein are incorporated by reference in their entirety . in case of conflict , the present specification , including any definitions , will control . in addition , the materials , methods and examples given are illustrative in nature only and not intended to be limiting . accordingly , this invention may be embodied in many different forms and should not be construed as limited to the illustrated embodiments set forth herein . rather , these illustrated embodiments are provided so that this disclosure will be thorough and complete , and will fully convey the scope of the invention to those skilled in the art . other features and advantages of the invention will be apparent from the following detailed description , and from the claims . with the foregoing in mind , an in vitro dormancy model that can be adapted to drug screening would help to discover antilatency drug candidates . in vitro models suitable for such screening are urgently needed . a number of different stresses have been applied to mtb in vitro in an attempt to generate a dormant state and gene expression changes have been investigated . most of these models involve single stress factors such as oxygen depletion , nutrient deprivation , no treatment and acidic conditions . the gene expression changes during combined nutrient deprivation and 10 % and 0 . 2 % oxygen stress on stationary phase cultures were investigated . some of these stress conditions such as prolonged nutrient starvation caused mtb to become highly rif - resistant but accumulation of storage lipids was not tested . on the other hand hypoxic conditions we used that caused tg accumulation did not develop resistance to 5 μg / ml rif ( unpublished ). the nrp - 1 condition was reported to cause resistance to a lower concentration of rif ( 1 μg / ml ) but lipid accumulation was not tested . we suggest that both rif - resistance and lipid storage are hallmarks of dormancy . since individual stress conditions do not allow the pathogen to fully meet these criteria , we attempted to mimic the in vivo conditions by applying multiple stresses thought to be encountered in vivo by mtb and tested whether the pathogen would accumulate storage lipids and develop rif - resistance . bacilli within granulomas encounter low oxygen ( 5 %) but not hypoxia , high co 2 ( 10 %) concentrations , low nutrient levels and acidic ph . based on these reports , we used 5 % o 2 , 10 % co 2 , ph 5 . 0 and 10 % dubos medium in a multiple stress in vitro model . our preliminary results show that the combination of the four stress factors leads to accumulation of storage lipids ( tg and we ), development of rif - resistance and gene expression changes thought to be associated with dormancy . some of the gene expression changes are similar to those found in the pathogen from infected lungs of hosts , including primates and a human tb patient . both rif - resistance and storage lipid accumulation are associated with dormancy . however , the commonly used in vitro hypoxia model , does not show both of these characteristics . therefore we developed a novel multiple stress model that applies four different stresses that the pathogen is thought to encounter in the host . we grew mtb cultures in low ph ( ph 5 . 0 ), low nutrient ( 10 %) dubos medium without glycerol , with high ( 10 %) co 2 and low ( 5 %) oxygen gas phase . mtb cultures in 10 % dubos ( difco ) medium at ph 5 . 0 at an od 600 of 0 . 2 were maintained under 5 % o 2 + 10 % co 2 + 85 % n 2 by replacing the air phase every other day ; oxygen levels did not change significantly during the two day period . after monitoring the progressive changes that happened to the pathogen , we chose to harvest cells at 3 , 9 and 18 days under such conditions for more detailed studies . these studies included examination of storage lipids , antibiotic ( rif and inh )- resistance , gene expression changes directly relevant to storage lipid synthesis by quantitative real time pcr ( qpcr ), and gene expression profiles by microarray analyses . tlc showed that we and tg accumulated under the multiple stress conditions reaching near maximal levels by 9 days fig1 . the major wax ester was oleyl oleate and the major fatty acids in the tg were c16 and c18 with less c26 ( data not shown ). under these conditions more we accumulated than tg in absolute amounts . control samples at ph 7 . 0 or ph 5 . 0 without additional stress showed no increase in storage lipids . nile red staining revealed storage lipid accumulation under the multiple stress conditions . it is well known that mtb cultures contain a heterogeneous population of cells under different physiological states . as the culture was subjected to multiple stress factors we observed decrease in acid fast staining cells with increasing lipid body staining cells from a barely detectable level to a significant percentage of the total cells by 18 days ( fig2 , 3 ). drug resistance was tested by treatment with 5 μg / ml rif for 5 days followed by serial dilution and plating . by 9 days about 10 % of the cells were found to be rif resistant whereas the starting culture contained about 0 . 03 % rif - resistant cells . rif - resistance increased up to 18 days , sometimes reaching up to 25 % at 5 μg / ml rif . the tgs1 ( rv3130c ) disruption resulted in the loss of rif - resistance which was restored in the complemented mutant ( table 1 ). hypoxic conditions , that were previously found to cause accumulation of storage lipids , did not cause the cells to develop detectable rif - resistance at 5 μg / ml . the tgs1 ( rv3130c ) disruption resulted in loss of tg accumulation under multiple stress . however the complemented mutant showed a level of tg accumulation comparable to the wild type ( fig4 ). gene expression changes directly relevant to storage lipid accumulation were examined by real - time pcr . among all the tgs genes , induction of tgs1 ( rv3130c ) was by far the highest at 9 days under the multiple stress condition , followed by rv3371 and rv3088 ( fig5 ). microarray analysis also indicated upregulation of rv3371 under multiple stress condition ( data not shown ). upregulation of rv3088 probably resulted from the low ph as it has been previously reported to be induced under acidic stress . up - regulation of rv3371 is noteworthy as it was also shown to be up - regulated in human lung granuloma by microarray analysis . the degree of induction of tgs1 ( rv3130c ) was comparable to that of icl and acr ( hspx ), genes previously reported to be induced during persistence . our preliminary experimental results raise the possibility that lipid accumulation under different stress conditions might use different sets of tgs genes . the tigr pathogen functional genomics resource center provided the mtb genome microarray for this study . under our multiple stress condition , genes that encode enzymes involved in glyoxylate cycle such as isocitrate lyase ( acea ) and citrate synthase ( glta1 ) showed significant increase in expression for all time points examined ( fig6 ). from these data we infer that the metabolic regulation of cells adapting to the multiple stresses was similar to that observed in persistent bacilli adapting to the phagosomal environment of a macrophage . under multiple stresses , mtb showed shutdown of both atp / nad energy regeneration systems . while gene expression for anaerobic respiration was continuously increased at the later time points , the aerobic respiration was significantly repressed at all the time points . all the subunits encoding nadh dehydrogenase and the ubiquinol - cytochrome c complex were repressed more than 2 - fold . in addition , the expression of the genes encoding atp synthase subunits was repressed . slowdown of the transcription / translation apparatus was evident during the multiple stresses . many genes related to transcription and translation apparatus were all consistently repressed . genes involved in modification of chromosome and cell division were repressed by the multiple stresses . the expression level of the gene cluster , mas , fad28 , mmpl7 , and ppsa - e , associated with phthiocerol dimycocerosate ( pdim ) synthesis and transport , that was repressed at the beginning of the multiple stress treatment , gradually increased more than two - fold and remained high throughout the period of in vitro multiple stress . further , the mas - like gene pks2 , which is responsible for encoding a hepta / octa - methyl branched fatty acid synthase , was highly expressed . these changes are consistent with the report that dormant cells have thickened walls . we also found significant induction of the genes classified as the stress response genes ( eg . hspx ) that has been suggested to play a role in maintaining long term survival within the host . the gene array analysis results were verified by qpcr analysis of selected test genes . repressed and induced gene transcript level changes indicated by microarray analysis were found to be consistent with the changes indicated by the qpcr method ( data not shown ). we investigated whether the lipid accumulation that occurs as a result of multiple stresses might be reflected in changes in buoyant density . we fractionated the culture on a percoll ® gradient in 10 ml seton easy - seal polyallomer centrifuge tubes with seton noryl crown assembly . this procedure resolved cells based on buoyant density ( fig7 ). the banding pattern changed as the cultures were subjected to multiple stresses for increasing duration . these changes are consistent with the conclusion that application of multiple stresses caused progressive changes in lipid accumulation resulting in increasing percentages of cells in the lighter fractions . auramine - o / nile red staining of the different fractions showed that with increasing periods under the multiple stresses , increasing percentage of cells became lipid - loaded and lost acid - fast staining ( presumably dormant cells ). staining of percoll ® fractions from 18 day stressed cultures showed that the lighter fractions were more enriched in , lipid loaded cells that lost acid - fastness . after this long stress period most cells were in the lighter fractions ( fig7 ). upon percoll ® density gradient fractionation of the 18 - day multiple - stressed culture , the great majority of the cells were distributed in the lighter fractions . when rif - resistance was assessed by the alamar blue dye method the lighter fractions showed a higher percentage of rif - resistant cells ( data not shown ). the small number of heavier cells present in this culture showed rif - susceptibility comparable to that of the starting culture . recent meta - analysis of mtb microarray data from many in vitro and in vivo conditions that are thought to induce dormancy ( murphy and brown , bmc infect . dis . i , 84 - 100 , 2007 ) indicated that a set of genes possibly involved in lipid storage and utilization are highly upregulated . we have determined the transcriptional profile of the genes , selected on the basis of the meta - analysis by real - time pcr using 7500 fast system ( applied biosystem ). detection of transcriptional upregulation of the known dormancy - responsive genes such as hspx , icl and dosr ( fig1 ) is consistent with our conclusion that the multiple stress conditions induce dormancy . seven of the 10 genes in the first priority group , such as rv3130c along with a few other tgs genes ( rv3371 , rv1760 ), a few genes encoding potential hydrolases ( lipx lipy , cut3 ), and fatty acyl - coa reductase gene ( rv3391 ) showed upregulation . three of the 21 genes in the next priority group showed upregulation under the multiple stress condition . one of them showed surprisingly high induction . the other two upregulated genes in this group were cut2 and lipz . only one gene ( rv2285 , a tgs ) in the third priority group showed upregulation . among the tgs products that showed the highest enzymatic activity ( when expressed in e coli ) only this tgs showed a preference for oleoyl - coa . we already have mutant for this gene and this mutant showed the second most impaired ability to accumulate tg under hypoxia as indicated in the preliminary results presented in the application . it is noteworthy that 7 of the 10 genes in the first priority group and 3 out of 21 genes from the second priority group and only one out of 17 in the third priority group showed upregulation . since the prioritization is based on meta - analysis of the degree of their upregulation under a variety of conditions thought to induce dormancy , our results suggest that the multiple stress model reflects real dormancy and adds validity to our approach . the tuberculous granuloma , which is thought to be a hypoxic environment , consists of a core of mtb - infected macrophages surrounded by lipid - loaded macrophages , mononuclear phagocytes and lymphocytes enclosed by a fibrous cuff . the differentiation of macrophages into lipid - loaded macrophages in tuberculous granulomas is a well - documented observation and the secretion of cytokines by the infected lipid - loaded macrophages probably helps to maintain the granuloma . histological studies revealed the presence of lipid - loaded macrophages in the granulomas of immunocompetent and hiv - 1 infected patients with tb . lipid - loaded macrophages contain abundant cytosolic stores of tg and cholesterol esters . a recent study showed that exposure of human macrophages to hypoxia ( 1 % o 2 ) converted them into lipid - loaded cells and m . bovis bcg infection induced the conversion of macrophages into lipid - loaded cells but the nonpathogenic mycobacterium smegmatis failed to induce lipid body formation . thus lipid bodies within mtb - infected macrophages may have important roles in pathogenesis and possibly in latency . human thp - 1 monocytic cell line - derived macrophages ( tdm ) are known to be converted into lipid - loaded macrophages . therefore they can serve as a more convenient experimental model for studies on mtb mutants , because their use can avoid the variability in responses encountered in the use of human peripheral blood monocyte - derived macrophages and provide a readily available uniformly reproducible cell model suitable for high throughput screening of drug candidates . lipid bodies have been found in mtb obtained from patients with active disease . however , the origin of these lipids remains unknown . the pathogen inside the lipid - loaded macrophages might utilize fatty acids derived from the lipid bodies in the host cells to store lipids within mtb for later use . such a possibility was raised by the recent finding that adipocytes might be a home for dormant mtb in humans . in fact , mtb inside adipocytes were found to accumulate lipid bodies while becoming dormant , as indicated by their resistance to killing by drugs . the lipid bodies found in the pathogen from patients probably originate from the lipid bodies in the macrophages . our results indicate that mtb within lipid - loaded macrophages can use the host &# 39 ; s tg to accumulate tg within the pathogen and this mtb becomes rif resistant meeting our criteria for dormancy . herein we disclose a newly developed thp - 1 derived macrophage ( tdm ) system for infection with mtb . thp - 1 cells , differentiated into macrophages by treatment with 100 nm pma for 3 days , were incubated for 3 days in 1 % o2 and 5 % co2 . oil red - o staining revealed lipid droplet accumulation in such macrophages ( fig2 ). when the tdm were infected with mtb at a multiplicity of infection ( moi ) of 1 . 0 for 4 hr and incubated in 1 % o 2 / 5 % co 2 for 3 days , lipid bodies accumulated in the host cells ( fig3 ). mtb cells within the macrophages showed nile red stained lipid bodies ( fig4 ). most mtb cells showed loss of acid fast staining and thus stained only red ; a few showed some acid fast and lipid staining ( yellow ). we modified our experimental protocol to allow for longer incubation of infected macrophages . we infected tdm with mtb at an moi of 0 . 1 ( 1 bacillus per 10 macrophages ) and extended the incubation of the infected tdm to 7 days under hypoxia . after 7 days , infected tdm were lysed and the cell debris was removed by centrifugation at 300 g for 10 min . the mtb cells were pelleted by centrifugation at 3000 g for 10 min and washed . lipids from the host - lipid bodies were extracted from the supernatant and the lipids from the pelleted to analyze fatty acid composition , host or mtb tg was purified by preparative tlc and the methyl esters generated by bf3 / methanol transesterification , were analyzed by capillary gc . the amount of fatty acids from the tg isolated from mtb , recovered for tdm , is more than enough for such gc analysis ( fig6 ) pathogens were extracted . tlc analysis of the lipids revealed that tg in the host cells was markedly increased by incubation under hypoxia for 7 days and the levels of tg were lower in infected tdm under hypoxia ( fig5 a ). lipids extracted from mtb recovered from infected tdm were also analyzed by tlc . we detected increased tg level in mtb cells recovered from tdm incubated under hypoxic conditions ( fig5 b ). the fatty acid composition of the tg from the pathogen was not identical to that of the host tg . c16 : 0 , c18 : 0 and c18 : 1 fatty acids were the dominant components in both the pathogen and the host . longer chain saturated fatty acids ( c24 , c26 and c28 ) that were present in the pathogen tg were absent in the host tg . we conclude that the tg that accumulated in the pathogen probably consisted of fatty acids from the host and some fatty acids generated within the pathogen . gene expression changes occurring in the pathogen within tdm were examined using a two - step real time pcr method . briefly , total rna was isolated and purified from a mixture of mtb - infected tdm using trizol ( invitrogen ) and qiagen rneasy column purification method . total rna was dnase treated twice , purified through qiagen mini elute rneasy column , purity of rna was checked at every step . controls without reverse transcription ( rt ) verified lack of dna contamination . first - strand cdna , synthesized with exo - resistant random hexamers and superscript iii reverse transcriptase ( invitrogen ) was used for multiplex pcr using many mtb gene specific primer sets . all primers and taqman probes were designed using visualomp6 software from dna software , inc ( ann arbor , mich .). the taqman probes have a fluorescein reporter dye ( fam ) at 5 ′- end and a black hole quencher ( bhq ) at 3 ′- end . each multiplex and real - time pcr primer was checked for specificity and efficiency . differences in mtb specific gene transcripts were quantified by real - time pcr on generated multiplex - pcr products with nested taqman primers and probes . the overall reliability and sensitivity of the two - step rt - pcr method to quantify gene expression profiling has been discussed in detail elsewhere . we have thus far done only a subset of genes thought to be relevant to lipid storage and metabolism ( fig7 ); icl was by far the most induced gene , consistent with the idea that the pathogen in tdm grows on fatty acids . it is noteworthy that lipy , that was previously shown by us to be involved in tg mobilization , was highly induced and some of the other lip genes also showed induction . dosr and tgs genes were also induced probably indicating their involvement in the storage of fatty acids derived from host - lipids as tg resynthesized within the pathogen , consistent with our hypothesis . fatp , that might be involved in fatty acid transport into the pathogen was also induced . putative fabp genes also showed some induction . these results indicate that our hypothesis concerning storage and mobilization of host lipids by the pathogen has real validity . we analyzed the resistance of mtb recovered from tdm after a 7 day incubation under 20 % o 2 or 1 % o 2 to rif and inh by cfu determination . tdm were infected with mtb at an moi of 0 . 1 . mtb cells inside tdm were exposed to antibiotic for 2 days prior to lysis of tdm and recovery of the bacilli . the recovered mtb cells were diluted and plated on agar plates without antibiotic and incubated for 4 weeks after which cfus were enumerated . antibiotic resistance is expressed as percentage of control without antibiotic . as indicated in table 2 , mtb recovered from tdm incubated under 20 % o 2 showed resistance to both antibiotics . others have found development of rif resistance in host cells . we found that rif resistance increased significantly in mtb recovered from tdm incubated under 1 % o 2 for 7 days compared to normoxic conditions . these results indicate support for our hypothesis that lipid - loading of macrophages favor the entry of mtb into dormancy . in making further progress developing the macrophage dormancy model , we tested different moi in the lipid loaded macrophage system . we assessed the viability of mtb - infected lipid - loaded macrophages under hypoxia under different moi . at moi 1 . 0 or higher the host cell viability was seriously compromised . at moi 0 . 1 , after 7 days under 1 % o 2 , 40 % of the original tdm population remained intact as an adhered monolayer and were loaded with lipid droplets . about 94 % of these lipid - loaded tdm cells in the adhered monolayer were viable . these results support the notion that these lipid - loaded tdms provide a tg - enriched sanctuary for mtb , favoring its entry into dormancy . we originally suspected that mtb utilizes the macrophage lipid bodies to acquire fatty acids and store them as tg within the pathogen to enable it to go through dormancy . to test this hypothesis , we labeled tdm lipids by incubating the cells with [ 14 c ] acetic acid or [ 14 c ] oleic acid , under 1 % o 2 for 2 days . these cells were washed three times with sterile phosphate - buffered saline ( pbs ) to remove unincorporated radiolabel . thin - layer chromatographic ( tlc ) analysis of the labeled lipids extracted from tdm showed that major part ( about 60 %) of the radioactivity in the lipids derived from labeled acetate and oleate was in tg that accumulated in tdm under 1 % o 2 . these pre - labeled cells were infected with mtb at an moi of 0 . 1 for 4 h under 1 % o 2 . following infection , extracellular mtb were removed by thoroughly washing the tdm monolayer with sterile pbs . infected tdm were incubated for 5 more days under 1 % o 2 . the host lipids and lipids from mtb recovered from the host cells were obtained and the lipids were analyzed by tlc . the fatty acid composition of the mtb and host tg was analyzed by resolving the intact tg and fatty acid methyl esters derived from tg on reversed - phase silica - tlc and argentation - tlc . analysis of intact tg from [ 14 c ] acetate in tdm was composed of saturated and unsaturated fatty acids . however , the tg of mtb was predominantly composed of saturated fatty acids as indicated by greater mobility on agno 3 - impregnated tlc ( fig8 a ). analysis of fatty acid methyl esters prepared from tg isolated from tdm and mtb indicated that the tg of mtb , recovered from tdm labeled with [ 14 c ] acetate , was composed primarily of saturated fatty acids , mostly 14 c - 16 : 0 and a very small quantity of 14 c - 18 : 0 fatty acids ( fig8 b , c ). see also table 3 , below . mtb recovered from [ 14 c ] oleic acid - labeled tdm had tg that was distinctly different in fatty acid composition from the tg in tdm . while the 14 c in tdm tg was predominantly in 18 : 0 ( about 81 % of total fatty acids ), 14 c in mtb tg was mainly in unsaturated fatty acids ( about 70 % of total fatty acids ). the identity of these fatty acids is to be determined . these results clearly indicate that mtb acquires fatty acids from tdm lipid bodies for synthesizing tg as a potential energy source . the tg stored within the pathogen probably includes the fatty acids from the host lipids and fatty acids generated by modification and / or catabolism and resynthesis . the biochemical processes involved can be deduced only after further characterization of the tg that accumulates in the host and in the pathogen . we also postulated that the mtb tgs gene products may be pivotally involved in synthesizing tg within the mtb cell from fatty acids acquired from host tg . to test this hypothesis , we infected the pre - labeled tdm with wild - type mtb and tgs1 ( rv3130c ) deletion mutant ( δrv3130c ) as described in the methods section . about 1 % of the radiolabel in the tg in tdm was found in the tg isolated from mtb . we quantitated the radioactivity in the tg of mtb and δrv3130c recovered from tdm . the results indicate that tg accumulation by the δ3130c was decreased by 90 - 95 % when compared to the wild - type ( table 3 ). these results additionally suggest that rv3130c plays an essential role in the accumulation of tg by mtb within lipid - loaded macrophages . in order to visualize the mtb inside lipid - loaded host cells , infected tdm after 7 days under hypoxia were fixed with 4 % paraformaldehyde and stained for mtb with carbolfuschin followed by methylene blue or hematoxylin and eosin to stain the host cell . mtb inside tdm were also stained with the mycolic acid - specific fluorescent dye auramine - o followed by nile red which stains neutral lipids . interestingly , as seen in fig9 , the mtb - infected tdm which were incubated under hypoxia for 7 days appeared to be fusing together . it is probable that these tdm are in the process of forming multinucleate giant cells ( asterisk in fig9 a ) which are known to be present in the hypoxic environment of the granuloma in close vicinity to lipid - loaded macrophages . these observations support the hypothesis that this lipid - loaded macrophage system is a good model for in vivo latency . individual mtb cells inside tdm that accumulated neutral lipids , as indicated by nile red staining , lost acid - fastness as shown by weak or total loss of auramine - o staining ( fig1 ). conversely , mtb cells which stained strongly with auramine - o did not accumulate neutral lipids . this accumulation of neutral lipids and loss of acid - fastness by a subset of mtb cells within lipid - loaded tdm under hypoxia , correlates well with our data in the preliminary results , that demonstrated the development of rif resistance by about 25 % of the mtb population and increase in tg within mtb from tdm under the same conditions . since then , we have reconfirmed these results with additional experiments . based on these results , the multiple stress in vitro latency model disclosed herein appears to be the best one available for screening chemicals to discover drug candidates that can eliminate latent pathogen . accordingly , in the drawings and specification there have been disclosed typical preferred embodiments of the invention and although specific terms may have been employed , the terms are used in a descriptive sense only and not for purposes of limitation . the invention has been described in considerable detail with specific reference to these illustrated embodiments . it will be apparent , however , that various modifications and changes can be made within the spirit and scope of the invention as described in the foregoing specification and as defined in the appended claims .	2
fig1 is a general view of xerographic copier 10 incorporating the present invention ; for example , a copier of the type which is designated as the ibm series iii copier / duplicator . in fig1 fuser assembly 12 is shown in its extended or pulled - out position in front of the copier , and is slidably supported within copier 10 by apparatus shown for purposes of simplicity . this is a nonoperating position adapted to facilitate inspection , cleaning , repair and / or sheet jam clearance . the slidably supported fusing assembly 12 includes a hot roll 14 and a backup roll 16 . generally , hot roll 14 is heated to an accurately controlled temperature by an internal heater 15 , as seen in fig2 and an associated temperature control system which is not shown . hot roll 14 preferably includes a deformable external surface formed as a thin elastomeric surface . this surface is designed to engage the toned side of a copy sheet which has a latent image formed thereon which was first located on a photoconductor surface ( not shown ). this image is transferred from the photoconductor to the copy sheet by first placing toner on the imaged surface of the photoconductor , with the toner adhering to the image formed thereon . next , a suitable transfer means is used to transfer this toned image to the copy sheet . hot roll 14 , acting in concert with backup roll 16 , fuses the image onto the copy sheet and readily releases the sheet with minimum adherance of residual toner to the hot roll . as is conventional in hot roll fusers , the sheet &# 39 ; s toned side faces the hot roll . backup roll 16 is preferably a relatively cool and rigid roll . both rolls 14 and 16 are circular cylinders and the fusing nip formed thereby defines a line ( of some width due to deformation of hot roll 14 ) parallel to the axis of rolls 14 and 16 . the fusing nip formed by rolls 14 and 16 may be opened and closed in synchronism with the arrival and departure of copy sheet leading and trailing edges , respectively . this synchronism is achieved by a drum position sensing means which responds to the position of the photoconductor drum and effects opening and closing of the nip by means of a copier control system ( not shown ). in the alternative , for a multi - copy run , the fusing nip may continuously remain closed until the trailing end of the last sheet has passed therethrough . fig2 shows the fusing nip closed . rigid backup roll 16 is shown to be in contact with resilient hot roll 14 , thereby deforming the surface of hot roll 14 so as to form a fusing nip 18 of a certain width , measured in the direction of sheet movement 19 . feed roller 20 cooperating with idler roller 21 continues sheet movement 19 until a copy passing therethrough is free of fusing nip 18 and has passed through fuser exit - way 22 . in fig3 hot roll 14 is removably , rotationally mounted on a fixed position axis in mounting blocks 23 which are supported by way of positioning surfaces 24 formed in the ends of a single piece mounting main frame member 26 . this main frame member 26 includes a hanger which supports the fuser assembly by way of telescoping rails 30 . frame member 26 also includes rollers 32 , or equivalent sliding bearings , which cooperate with a copier frame member to stabilize the fuser assembly position within the copier . as seen in fig3 and 13 , roll 16 is rotationally supported , on axis 34 , by way of pivoting cradle arms 36 at each end of frame member 26 . these cradle arms are pivoted on the frame member at axis 38 . pivot arms 40 , at each end of main frame member 26 , are pivotably mounted to the frame member by way of pivot 42 . pivot arms 40 have downwardly extending projections 41 which support rollers 44 which cooperate with nip opening and closing cams 46 . the other ends of pivot arms 40 have mounted thereon ends 48 of compressible force - cells 50 . the other ends 52 of force - cells 50 operate on cradle arms 36 to cause arms 36 to rotate clockwise about axis 38 , force cells 50 provide controlled pressure to backup roll 16 through axis 34 , and consequently the pressure to fusing nip 18 is controlled . springs 53 , positioned between hanger 28 and pivot arms 40 , provide an additional opening force to fuser nip 18 . the closing of fusing nip 18 is achieved by cams 46 which are rotationally mounted on axis 38 . these cams include a low point 54 which , when positioned to cooperate with roller 44 , establish a nip - open condition . to close the nip , solenoid 56 is energized and clutch 58 , shown in fig4 - 6 , operates to rotate cams 46 , in fig3 clockwise 235 ° ( counterclockwise if observing fig4 ) to the position shown , causing nip 18 to close . during nip closure , pivot arms 40 ( see fig3 ) rotate counterclockwise causing fixed - position pivot 42 , force - cell pivot 60 and axis 34 to come into substantial alignment . however , pivot point 60 does not move overcenter . thus , subsequent rotation of cams 46 , back to the nip open cam position 54 , as a result of the deenergization of solenoid 56 , allows force - cell 50 to rotate pivot arms 40 clockwise ( when observed on fig3 ) about pivot 42 , opening fusing nip 18 . cams 46 are connected to rotate on axis 38 as long as clutch member 58 ( fig5 and 6 ) is free to rotate . in the deenergized position of solenoid 56 , dog 62 is held against rotation by tab 70 on pivoting link 66 . link 66 is pivoted at fixed position pivot 68 . when solenoid 56 is energized , clutch member 58 and cam 46 are driven 235 ° until dog 62 engages tab 64 . fusing nip 18 is now closed . subsequently , when it is desired to open the fusing nip , solenoid 56 is deenergized , link 66 returns to its deenergized position , and clutch member 58 rotates until it is stopped by tab 70 . fusing nip 18 is now opened . the above - described means for opening and closing the fusing nip is more specifically described and claimed in a copending application , entitled &# 34 ; hot roll fuser roll closure apparatus &# 34 ;, ser . no . 826 , 619 , filed aug . 22 , 1977 , and assigned to the same assignee as the instant invention . in the fragmented portion of fig4 a folded hot roll handle 72 , for manually removing hot roll 14 , is shown . the use of this handle for removing hot roll 14 from the fusing assembly will be explained hereinafter . in fig1 , a manually movable , rod - like handle 74 extends the length of the fuser assembly , parallel to axis 34 . opposite ends of this handle are attached to movable links 76 , at each end of the fuser assembly . in fig7 and 8 it is seen that these links are pivoted on fixed - position axis 78 . both of the links have a notch 80 , and a pivot point 82 for one end of a drive arm 84 . in fig7 links 76 are shown in their operative positions , wherein the hot roll detach bar , 101 of fig2 and the fuser &# 39 ; s output sheet transport channel or exit - way , 22 of fig2 are located closely adjacent the downstream portion of fusing nip 18 , shown closed in fig2 . u . s . pat . no . 3 , 955 , 813 , commonly assigned and incorporated herein by reference , describes this sheet output channel and describes and claims and detach bar . fig1 is similar to fig7 of u . s . pat . no . 3 , 955 , 813 , and shows the pneumatic detach means incorporated within detach bar 101 . fig1 is a view of bar 101 with the leading edges 188 of a copy sheet 189 emerging from fusing nip 18 . the flow of air from nozzle 182 , into the gap formed by hot roll 14 and backup roll 16 , is complex and not completely understood . however , it is believed that air begins to flow tangent to the hot roll , as shown at 190 . it then follows the roll &# 39 ; s contour , rather than flowing in a straight line , due to the well known coanda flow effect . this flow pattern continues until the flow reaches the obstruction created by the fusing nip . this obstruction causes stagnation and lateral division of the airflow . in this stagnation process some of the jet &# 39 ; s kinetic energy is converted to an increase in pressure which propogates upstream toward orifice 182 and causes the jet to separate as shown at 194 . as a result , pressure differentials are created above the sheet . as the leading edge 188 of the copy sheet enters this flow , it is subjected to a force lifting it off roll 14 . in addition , the forward facing step created by the sheet &# 39 ; s leading edge , due to the paper &# 39 ; s thickness , aids in separation of the leading edge by presenting another obstacle to jet flow . in fig7 and 13 , links 88 are pivoted on fixed - position axis 90 . each of links 88 has a projection 92 thereon for holding mounting blocks 23 securely within main frame 26 . links 88 carry locking pins 96 which lock links 88 , and the detach bar 101 , in operative position by virtue of an interface at 98 between pin 96 and pivotable link 100 . links 100 are pivoted on fixed - position axis 102 . the ends of output sheet transport channel 22 are attached to links 106 . these links are pivoted on backup roll axis 34 . axis 34 is not a fixed - positioned axis because during nip closure , axis 34 moves a slight distance downward , as represented by arrow 108 in fig7 . the upper end of links 106 carry a locking pin 110 , cooperating with notch 80 formed in links 76 . the lower end of links 106 carry lower pivot axis 112 for the end of drive arm 84 that is opposite pivot point 82 . in fig8 two tension springs 114 extend between pins 116 carried by links 76 and pins 118 carried by links 100 . the springs provide a closing force between links 76 and links 100 . in addition to providing a closing force between links 76 and links 100 , springs 114 provide a contacting force between pins 96 and pivotable links 100 . the above - mentioned interface 98 is created by these latter two sets of links . in order to move the above - mentioned detach bar and output sheet transport channel out of the way for jam clearance and / or to remove hot roll 14 , the above - mentioned rod - like handle 74 is lifted up and rotated counterclockwise about fixed - position axis 78 , to the position shown in fig8 . this causes the detach bar to generally rotate clockwise about hot roll 14 away from fusing nip 18 , and the output sheet transport channel to generally rotate counterclockwise about backup roll 16 . during such movement , pins 116 on links 76 engage links 100 and cause these links to pivot counterclockwise about their fixed - position axis 102 . as a result , interface 98 , as seen in fig7 created by contact between pins 98 and pivoted links 100 is broken . in fig8 as handle - actuated links 76 continue to rotate counterclockwise , notches 80 free pins 110 . counterclockwise rotation of links 76 transmits counterclockwise rotation to links 106 by virtue of drive arms 84 . as pivot axis 112 moves counterclockwise as represented by arrow 120 in fig7 to its position in fig8 links 106 are pivoted clear of fusing nip 18 . as counterclockwise rotation of links 76 continues , surfaces 122 formed thereon engage locking pin 96 , causing links 88 to rotate clockwise about their fixed - position axis 90 . the detach bar and output sheet transport channel have now been moved out of the fusing nip for manual sheet jam clearance . in addition , link 88 has been pivoted clockwise , eliminating the interface between projection 92 on links 88 and mounting blocks 23 . links 88 can now be manually rotated clockwise , as represented by arrow 124 in fig8 in order that hot roll 14 can be removed from main frame 26 . in summary , interface 98 locks the detach bar in operative position , notch 80 and pin 110 lock the output sheet transport channel in operative position , spring 114 maintains interface 98 , pin 116 lifts link 100 to interrupt interface 98 , counterclockwise rotation of link 76 frees pin 110 and rotates link 106 by virtue of drive arm 84 , and counterclockwise rotation of link 76 rotates link 88 clockwise as a result of interference with locking pin 96 . a jam clearance means of the above - mentioned generic type is described and claimed in copending application ser . no . 771 , 126 , filed feb . 22 , 1977 , now u . s . pat . no . 4 , 110 , 068 , and assigned to the assignee of the instant invention . fig9 shows the fixed center drives for ( 1 ) producing rotation of the fuser &# 39 ; s backup roll 16 , ( 2 ) producing oscillatory movement of the backup roll &# 39 ; s scraping blade cleaner 126 , and ( 3 ) producing rotation fo the fuser &# 39 ; s paper exit guide transport roller 20 . roller 20 is supported by the exit paper transport guides , and engages the non - toner side of a sheet , as the sheet emerges from fusing nip 18 . additional information pertaining to the blade cleaner 126 appears in ibm technical disclosure bulletin , volume 18 , no . 2 , july 1975 , pages 326 - 327 . counterclockwise rotation of backup roll 16 is produced by gear 132 which meshes with continuously driven gear 134 . gear 132 is connected to the backup roll &# 39 ; s axis 34 and causes counterclockwise rotation of this roll . when the fusing nip is being closed or opened , the backup roll &# 39 ; s rotational axis 34 moves in an arc about axis 38 . thus , gear 132 merely rolls about its meshing gear 134 . cleaner 126 is supported by double helix lead screw 138 . this lead screw is driven in a counterclockwise direction by virtue of gears 140 - 142 with gear 140 being fixedly mounted on an end of lead screw 138 , gear 141 being rotatively mounted on fixed axis 144 and gear 142 being fixedly mounted on axis 34 . since all of these gears are carried by cradle arm 36 , a fixed center relationship is maintained during nip opening and closing . as a sheet of newly fused copy paper emerges from the fusing nip , and as it is driven by counterclockwise rotation of backup roll 16 , its leading edge is guided into the output sheet transport channel ( not shown in fig9 ). this sheet channel is supported by pivoting links 106 . links 106 supported at the rear end of the fuser , and shown in fig9 and 13 , carry a pair of gears 146 , 148 which mesh with a gear 150 which is integral with backup roll 16 . counterclockwise rotation of sheet transport roller 20 by gears 146 , 148 and 150 transports the copy paper out of the fusing nip . roller 20 cooperates with idler roller 21 , shown in fig2 to trap the copy sheet therebetween . the idler roller engages the toned side of the copy sheet . when the fuser &# 39 ; s sheet detach bar and output sheet transport channel are manually moved out of the way , as for jam clearance , links 106 rotate in a counterclockwise direction as discussed above with reference to fig7 and 8 . since link 106 pivots about the backup roll &# 39 ; s rotational axis 34 , a fixed center is maintained for gears 146 - 150 , and gears 146 and 148 merely rotate in a circle about gear 150 . consequently , a constant center distance between the gears is maintained and transport roller 20 is driven with minimum backlash by the gearing . the fuser &# 39 ; s main frame member 26 , shown in fig1 and 11 , comprises a central portion surrounding , but spaced from , the surface of hot roll 14 and having upstanding end flanges establishing the various rotational axes of the backup roll and its associated structure . these end flanges include u - shaped slots or positioning surfaces 24 adapted to receive the ends of the reversible hot roll . with reference to fig1 , hot roll 14 is rotationally mounted in rigid u - shaped subframe member 152 which is symmetrically located between positioning surfaces 24 . subframe 152 is locked to main frame 26 and is unlocked therefrom by rotation of rotatable handle 74 . a handle 154 shown folded in fig1 and shown extended in fig1 , is mounted on the central portion of subframe member 152 . each end of the not roll is supported for substantially frictionless rotation in metal end blocks 23 . end blocks 23 each have a stub shaft which fits into bearings at both ends of hot roll 14 . hot roll 14 is easily replaceable because metal end blocks 23 are removable from subframe 152 . these end blocks are substantially identical , the only exception being that one end block cooperates with a helix compression spring 160 which axially biases hot roll 14 towards the other end block for retention purposes . end blocks 23 nonrotationally support heating element 15 , as also seen in fig2 on the hot roll &# 39 ; s axis of rotation . a hot roll core temperature sensor ( not shown ) is mounted on main frame 26 under and in contact with hot roll 14 . hot roll 14 is driven in a clockwise ( fig2 ) direction by frictional engagement with counterclockwise rotating backup roll 16 when the fusing nip is closed . as seen in fig1 , both end blocks 23 have a mounting channel 164 . channels 164 are of uniform cross - section and run perpendicular to the hot roll &# 39 ; s axis of rotation . as shown in fig1 and 11 , the back mounting channel only of main frame member 26 includes a positioning pin 166 adapted to mate with channel 164 in the end block adjacent helix compression spring 160 . the front positioning channel of main frame member 26 , however , does not include such a positioning pin . each end of the reversible subframe member 152 , in fig1 , includes an electrical connector portion 168 , one of which is exploded and separated from end block 23 to illustrate electrical connector 170 . connector 172 is insulatively mounted on the main frame member &# 39 ; s forward end flange . the rear one of these connectors 168 is maintained in a fixed position by virtue of locking engagement between channel 164 and pin 166 . electrical connector 170 experiences movement along the axis of the hot roll as the temperature of the hot roll &# 39 ; s u - shaped subframe member 152 changes . metallic u - shaped subframe member 152 expands and contracts with temperature changes . however , since connector member 172 has a channel extending in a direction parallel to the axis of the hot roll , sliding movement of connector 170 within the channel of member 172 is accommodated . paper is fed through the copier with its long dimension parallel to the hot roll &# 39 ; s rotational axis , and with sheets of various sizes referenced to a common rear side edge ( corresponding to the common corner registration for all original documents to be copied on the master document support glass ). this rear edge is indicated by broken line 174 in fig1 . the forward edge of an 81 / 2 × 11 inch sheet of paper would reside at broken line 176 , whereas the forward edge of and 81 / 2 × 14 inch sheet of paper would reside at broken line 178 . the hot roll &# 39 ; s variable forward working area 176 - 178 makes it desirable to reverse hot roll 14 , end - for - end , periodically to distribute wear on the hot roll . before removing subframe 152 and hot roll 14 out of the fuser assembly 12 , subframe 152 is unlocked from main frame 26 by actuating rotatable handle 74 and movable links 76 which rotate links 88 clear of mounting blocks 23 . a shroud ( not shown ) which overlies hot roll 14 is pivoted clear of the roll and foldable handle 154 is unfolded to allow for the lifting of hot roll 14 , including subframe 152 , out of main frame 26 . with reference to fig1 , as subframe 152 is lifted , the connection between positioning pin 166 and channel 164 in end block 23 is broken . the electrical connection between the male and female connectors on the other end block 23 and main frame 26 respectively , is also broken . the upward motion of subframe 152 continues and end blocks 23 continue sliding until free of positioning surfaces 24 . once out of main frame 26 and the fusing area , subframe 152 is reversed , end for end . after reversal of subframe 152 , the above steps are reversed until subframe 152 is again locked to main frame 26 . even though the handle for lifting subframe 152 out of the copier is shown and described as being permanently attached to subframe 152 , it should be understood by those having skill in the art that modifications to the handle - subframe configuration can be made . for example , handle 154 could be detachable and stored until needed to remove subframe 152 from the copier . these simple manual steps allow hot roll reversal to be accomplished within a short period and also reduce the risk of component damage due to handling . additionally , the hot roll core temperature sensor is not disturbed during reversal of the hot roll . the use of handle 154 for removing hot roll 14 from the fusing assembly is more specifically described and claimed in a copending application , entitled &# 34 ; apparatus for the reversal of a hot roll in a fusing assembly &# 34 ;, ser . no . 820 , 272 , filed july 29 , 1977 , now u . s . pat . no . 4 , 121 , 089 , and assigned to the same assignee as the instant invention . while the invention has been shown and described with reference to a preferred embodiment thereof , it will be appreciated by those of skill in the art that variations in form may be made therein without departing from the spirit and scope of the invention .	6
fig1 illustrates a first embodiment of a medical shaft - type instrument 1 . it comprises an instrument handle 2 on its proximal end . in brief , the instrument handle 2 may also be referred to as a handle . the handle may be designed in the manner of a “ challenger handle ”. an instrument head 3 is formed on the distal end of the medical shaft - type instrument 1 . arranged between the instrument handle 2 and the instrument head 3 is an instrument shaft 4 connecting the two components to each other . the instrument shaft 4 comprises an external outer tube 5 . the outer tube 5 may have an annular cross - section and be formed in the manner of a hollow cylinder . the instrument handle 2 acting as a contact area for a hand forwards an instruction of an operating surgeon to the instrument shaft 4 in order to actuate the instrument head 3 by means of it . a clip magazine 7 is present within the outer tube 5 functioning as a housing 6 . the clip magazine 7 is a magazine for storing clamps , clips , brackets or other clamping configurations suitable for ligature use . such clamps , in particular ligature clamps or clips are provided for being plastically deformed or locked in place , in order to stanch an organ of a mammalian , for instance a blood vessel of a human , in the deformed state . a plurality of such clamps 8 is represented in fig2 . fig2 shows the individual parts of the medical shaft - type instrument 1 , without the instrument handle 2 . in particular , an upper jaw part / an upper jaw part branch 9 , a lower jaw part / a lower jaw part branch 10 , a slider 11 which may be referred to as a cam carrier component and a retaining rail 12 can be seen . in the embodiment illustrated there , twenty clamps 8 are utilized in total . it would also be possible , however , to use a higher or smaller number of said clamps 8 . a tongue 13 which may also be referred to as a feed tongue , a feed divider 14 , a spring support 15 and a transport and entraining rail 16 which may also be referred to as a feed rail , are also included . further , a feed spring 17 , a sealing disc 18 , a feed rod / pusher rod 19 and a feed rod end piece 20 are used . a pusher tube 21 adjoins a sealing ring 22 . the sealing ring 22 is a distal limitation of a compression spring 23 which is adjacent to a spring flange 24 . the compression spring 23 is supported on the spring flange 24 . the compression spring 23 is responsible for a return motion of the jaw parts 9 and 10 , hence for moving the upper jaw part 9 away from the lower jaw part 10 . the components 9 to 24 are provided for being inserted within the outer tube 5 . the outer tube 5 is inserted in a handle flange 25 after the assembly process . the handle flange 25 for its part is in a force - fitting , form - fitting and / or material - bond type contact with a handle piece / handle coupling component 26 in order to connect to the instrument handle 2 . a hollow cylinder end piece 27 is arranged proximally with respect to the spring flange 24 . said hollow cylinder end piece 27 as well as the feed rod end piece 20 can be seen as proximally protruding from the handle piece 26 . fig3 illustrates the components known from fig2 in the assembled state . fig4 to 6 suggest the assembly unit made up of the upper jaw part branch 9 and the lower jaw part branch 10 for receiving the most distal clamp 8 within a shell form 28 . a retaining rail 12 formed as a metal retaining plate is arranged below the transport and entraining rail 16 . fig7 allows to clearly see the guidance of the clamps 8 in a cross - sectional view . as can be seen , the clamp 8 illustrated there has its four clamp webs 29 supported on the retaining rail 12 as well as on the outer tube 5 . the clamp webs 29 may be briefly referred to as webs . in this arrangement , the outer tube 5 comprises contact surfaces / abutment surfaces 30 for contacting the upper clamp webs 29 of the clamp 8 . the clamp 8 is designed here in the manner of a double - web clip . the tongue 13 is provided for ejecting the foremost , first clamp 8 , i . e . the most distal clamp 8 , whereas the transport and entraining rail 16 is provided in the manner of a metal feed plate for moving all the clamps 8 in the clip magazine 7 . the contact surfaces / abutment surfaces 30 are designed such that they allow a sliding motion of the clamps 8 along it . optionally , but not illustrated , the outer tube 5 — in the area of the contact surface 30 intended for being contacted by the clamp webs 29 — may be provided with recesses such as slots , grooves , serrations or through - holes , through which the clamps 8 may project outwards to the outer side of the outer tube 5 , i . e . so as to penetrate the outer tube 5 . this allows to achieve a particularly compact configuration of the shaft - type instrument 1 . the clamps 8 also rest on the retaining rail 12 with their clamp webs 29 , in fact in such a manner that a compression / deflection of the clamps 8 is forced in cooperation with the support on the outer tube 5 . the clamps 8 do not contact each other here . the tongue 13 is fed through the double - web clip - like clamps 8 , resulting in a sort of threading of the clamps 8 . in this arrangement , the clamp webs 29 form leg portions . the feed motion of the clamps 8 is effected by a forward and rearward movement of an elongated component comprising lugs in the style of protrusions , lamellas or barbs . the clamps 8 are exclusively guided on an inner wall 31 of the outer tube 5 and on a sheet - metal type retaining rail 12 . this results in an effective use of the installation space . noises , in particular rattling noises , are prevented . this results in a precise guidance . a compensation of the tolerances is achieved as well . a separate channel is not required . a channel - like construction as shown in fig7 is sufficient here , and the use of metal sheets has advantages in terms of dimensioning the stiffness . the retaining rail 12 comprises retaining lugs 32 . these can be clearly seen in fig1 to 16 , for instance . in said figures , a butterfly - type segmentation of the retaining lugs 32 into a first retaining lug portion 33 and a second retaining lug portion 34 can be seen as well . thus , these two retaining lug portion 33 and 34 constitute a kind of butterfly lug . the wings of a butterfly lug may also be referred to as first and second retaining lug portions 33 and 34 . the clamp webs 29 , which may also be designated as legs , slide / slip over the retaining lug portions 33 and 34 and result in the retaining lug portions 33 and 34 folding along a swivel or bending line 35 . the swivel or bending line 35 may also be referred to as a bending axis or swivel axis . as can be clearly seen especially in fig1 and 16 , a movement of the clamps 8 in proximal direction is prevented by a proximal end of the clamp 8 resting against a distal edge 36 of the retaining lug 32 . as can be clearly taken from fig1 and 16 , the shape of the lugs is also implemented in a butterfly - type shape . the protruding lugs including wings having the largest possible edge / area for supporting the clamps 8 on the clamp &# 39 ; s back should offer a high rigidity . the geometry of the retaining lugs is designed such that it can get out of the way during the run - over process , without going below the level of the metal sheet . in other words , the retaining lugs 32 lay down flat . in the erected state , side edges 37 of the retaining lugs 32 form lines which are almost parallel . they extend predominantly in the longitudinal direction . at least an angle from proximal larger than 0 ° is acceptable . this provides for minimum friction . if the clamp 8 runs over the retaining lug 32 from proximal , this angle will be enlarged . looking ahead to fig1 , it is mentioned that also the transport and entraining rail 16 comprises lugs , namely clamp entraining elements or clamp entraining lugs 38 . increments and distances of the lugs are important for the limitation of the length of the component , in particular for the length of the magazine . they dictate the work of friction . they have to be arranged in a skillful way with respect to their position in relation to the feed hub which may also be referred to as a delivery stroke . they can be formed in a simple manner if a shaped metal strip or a plastic component is used as a starting base for them . they should be arranged preferably in the style of springy lugs with precisely defined distances . the mutual distances between the retaining lugs 32 may be variable along the length of the sheet metal , i . e . does not have to be kept constant . the distances of the clamp entraining elements / lugs 38 relative to each other should also be variable along the length of the sheet metal , i . e . should not remain constant . the spacing increments of the lugs should be selected such that a sequential collecting of the clamps 8 is carried out starting from a rest position of the clamps 8 , resulting from non - constant distances . this has the effect of a continuous increase of force . in that case , a predetermined amount of a force to be applied will not be exceeded . the spacing increments of the lugs should be selected such that the length of the magazine is minimized . the spacing increments of the lugs are selected here such that the collecting process occurs sequentially from distal to proximal depending on the rest position of the clamps in order to avoid a mutual collision of the clamps or counteract it . the following relationship is suitable for the determination of the spacing a : the spacing ( a ) is referred to as the spacing between the j th and the ( j − 1 ) th lug either of the retaining rail 12 or of the feed rail / transport and entraining rail 16 , with j specifying the position of the lug starting from distal and n corresponding to the total number of the clips in the applicator . spacing of the retaining lug ( arhl )= constant spacing ( ak )+ incremental spacing rhl ( ajrhl ) incremental spacing rhl ( ajrhl )= increment rhl ikrhl ·( n − j ) spacing of the feed lug ( avsl )= constant spacing ( ak )+ constant ( k )+ incremental spacing vsl ( ajvsl ) incremental spacing vsl ( ajvsl )= increment vsl ikvsl ·( n − j ) however , the constant spacing ( ak ) depends on the clamps , their size and their geometry and amounts to approximately 8 . 5 mm , for example . it is also possible to provide a constant increment ( ik ) and a variable increment ( iv ). the total increment i is then calculated as follows : i = ik + iv . this allows to determine the location of the occurring maximum force and hence the buckling of the sheet metal . fig8 illustrates the friction - related behavior as a function of the position where the clamp 8 runs over one of the lugs 32 and 38 . the abscissa shows the length of the lugs in mm , whereas the ordinate shows the total force f ges in newton . in fig9 is an illustration of the increase in force during “ collecting ” the clamps 8 in the course of a delivery stroke , on the one hand , and in the course of a return stroke on the other hand , due to the friction when all the clamps 8 run over all the lugs ( retaining lugs 32 and clamp entrainment lugs 38 ). here , the solid line represents the increase in force / force progression during the feed motion / delivery stroke , and the broken line represents the increase in force / force progression during the return stroke . the abscissa shows the feed travel in mm , whereas the ordinate shows the need of physical force in newton . returning to fig1 and 18 , reference is made to the sandwich - like arrangement of the transport and entraining rail 16 above the tongue 13 which for its part is situated above the retaining rail 12 . thus , the retaining rail 12 , the transport and entraining rail 16 and the tongue 13 are arranged one above the other and so as to be axially movable . the lug heights of at least some of the lugs 32 and / or 38 are dimensioned here such that they guide the tongue 13 situated in the middle . in consideration of the fig1 to 21 , it should be obvious that it is desirable to achieve a feed motion division by means of an elongated hole 39 which is engaged by a cam 40 . the cam 40 protrudes from a feed divider 41 which may be designed so as to be separate from a spring support 42 . the cam 40 may be an integral constituent part of the spring support 42 . in any case , the feed rod 19 extends through the spring support 42 and is connected to the feed divider 41 in an axially fixed manner . the cam 40 of the feed divider 41 extends through the elongated hole 39 of the transport and entraining rail 16 . the tongue 13 is connected to the feed rod 19 in an axially fixed manner , so that any movement transferred from the feed rod 19 is directly imparted to the tongue 13 and passed on to the transport and entraining rail 16 not until the cam 40 impinges on a stop edge 43 . in this way , two engaging components are configured such that a pin , a cam or any other protrusion engages in a hole , a groove or a recess such that an axial relative movement of the two parts with respect to each other by a specific amount is allowed , but a combined movement is caused upon reaching a stop . as can be seen particularly well in fig1 and 20 , the spring support comprises recesses 44 which can be engaged by protrusions or lugs of the outer tube 5 in order to bring about an axial fastening . the fig2 and 23 show a variant differing therefrom , namely a variant in which the pusher rod 19 is directly connected to the tongue 13 . to this end , the tongue 13 is crimped around a distal end of the pusher rod 19 in the manner of a folded sheet . it goes without saying that the tongue 13 may also be an integral constituent part of the pusher rod 19 . with the configuration of fig2 and 23 , there is no separate feed divider 41 . however , said folded sheet 45 which provides for the connection between the tongue 13 and the pusher rod 19 vertically engages an elongated hole 39 provided in the transport and entraining rail 16 , in order to come in contact with a stop edge 43 — similar to the exemplary embodiment as described above — to bring about the initiation of the delivery stroke on the transport and entraining rail . whereas fig2 illustrates a perspective view predominantly from below , fig2 shows a longitudinal section . it is possible that the tongue 13 is glued to the pusher rod 19 , welded to it or crimped with it . in the end , two very precise stops are made available , allowing a very accurate working with the medical shaft - type instrument 1 . the retaining rail 12 does not only have a retaining function for the clamps 8 , namely the prevention of the return motion of the clamps 8 during the return stroke into the neutral position of the transport and entraining rail 16 , but ( as seen in cross - section ) also defines the lower limitation of the clip line formed by the clamps 8 . further , the retaining lugs 35 should be realized in the manner of barbs which can be run over in one direction by the clamps 8 and can also be displaced by the latter . the retaining rail 12 is also supposed to be fixed on the tube wall of the outer tube 5 by means of retaining rail mounting lugs 46 which can be seen in fig2 to 27 . to this end , a mounting hole 47 is provided in the outer tube 5 . the mounting hole 47 is worked into the material in the form of a slit for instance by means of a laser cutting procedure . an outer tube fold area 48 , provided in the manner of a lug and comprising an inspection window 49 , is bent radially inwards and offers sufficient space so that the retaining rail mounting lug 46 can engage below a lower edge 50 limited by the outer tube fold area 48 . this results in an axial stop toward the proximal end , provided with the reference symbol 51 , and an axial stop toward distal , provided with the reference symbol 52 . a height fixation means 53 is realized by the lower edge 50 . the mounting hole 47 is shaped in the manner of a window . the inspection window 49 is for checking purposes during the assembly process . in this way , a self - catching system is realized . the outer tube fold area 48 , which acts as a lug and is formed in one piece on the outer tube 5 , catches the retaining rail mounting lug 46 which is a single constituent part of the retaining rail 12 formed as a metal retaining plate and fixes the metal retaining plate at a predetermined level and in an axial position . the sequence during the assembly process is apparent from the fig2 to 27 which show the assembly protrusions of the retaining rail 12 from proximal to distal , caught under / caught by the outer tube fold area 48 with the retaining rail mounting lug 46 . fig2 shows the completely assembled state . a modified exemplary embodiment is shown in fig2 in which the retaining rail 12 is fixed on the spring support 42 by means of cut - outs . the spring support 42 for its part is already immobilized on the outer tube 5 in radial and axial direction . in this arrangement , the spring support 42 comprises cams 54 , which penetrate the retaining rail 12 and fix both components to each other in a form - and / or force - fitting manner . here too , a cam 40 enters an elongated hole 39 , so that a limitation of the delivery stroke is reached if the cam 40 hits the stop edge 43 , which is advantageous with a force - controlled use of the handle . in fact , the handle switches over the direction of movement as from a specific limit value on . an active retraction of the transport and entraining rail 16 and of the tongue 13 is then possible . fig2 to 31 have their focus on a distal end of the retaining rail 12 . at this place , a bridge / abutment plate 55 is formed which facilitates the gliding of the clamp 8 into the shell forms 28 of the upper jaw part branch 9 and the lower jaw part branch 10 . the bridge / abutment plate 55 may also be referred to as a cover for the lower jaw part 10 . in addition , a retaining rail mounting hole 56 is provided , which is arranged between the bridge / abutment plate 55 and a kicker - or ski jump - like deflector 57 . this deflector 57 serves in the manner of a kicker for lifting the clamp 8 at its tail , i . e . at its proximal end , so that the clamp 8 slides better into the upper and lower jaw part branch 9 and 10 , respectively . the deflector 57 also serves for stiffening purposes . during the assembly process , the retaining rail mounting hole 56 is used by an assembly tool ( not shown ), in order to be hooked in place there . in fig3 , laterally protruding retaining rail mounting lugs 46 offset in longitudinal direction are connected to each other by a ( theoretical ) asymmetrical bending line 58 , so that the ( theoretical ) direct bending line 59 provided with the reference symbol 59 does not occur . such a direct bending line 59 orthogonal relative to the longitudinal direction is avoided , as asymmetrical bending lines 58 are preferred in the event of the occurrence of critical torsional forces , because torsional forces do not occur here . spring lugs 60 which serve for supporting the retaining rail 12 on the pusher tube 21 can be seen in fig3 . thus , a residual force is made available which tries to decrease the clip channel into which the clamps 8 are directed . this results in a mutual stabilization of all components and prevents the clamps 8 from missing the retaining lugs 32 upon retraction . otherwise , retaining lugs 32 having a larger height and requiring more power would then be necessary , which would result in higher friction , entailing an increased physical effort during the feed motion process . in the end , a compensation of tolerances is also achieved by the spring lugs . as an alternative or in addition , the spring lugs 60 could rest on the upper and / or lower jaw part branch 9 and 10 , respectively . fig3 to 43 have their focus on the tongue 13 and its special configuration . the tongue 13 has its distal end provided with a tissue - protecting protrusion 61 which prevents that any tissue of the organ to be treated enters the area between the clamp webs / legs 29 of the clamp 8 and is pinched here unintentionally . the tissue - protecting protrusion 61 may also be referred to as a tissue spacer 61 . at a site proximal relative thereto , a notch 62 is provided which forms an insertion opening 63 . the insertion recess may be synonymously referred to as insertion opening 63 . as can be seen particularly clear in fig4 and 41 , this insertion opening 63 allows the proximal portion of the clamp 8 , namely the clamp web / leg 29 , to swivel or enter into the free zone provided by the notch 62 . the insertion opening 63 may also be referred to as an insertion recess and makes it possible that a portion of the clamp 8 projects from below into the notch 62 at least by some extent or even right through it . further , a protrusion in the manner of a movement - guiding element 64 is formed on the underside of the tongue 13 . this movement - guiding element 64 is formed in the manner of a deflector 65 or pilot bead 66 . it has the effect of increasing the flexural rigidity and at the same time provides for a catching protection . the catching protection prevents the clamp 8 from undesirably contacting the tongue 12 in the area of impact edges 67 , as otherwise the clamp 8 would be moved in axial direction ahead of time or in the wrong sense . abutment edges 68 for providing a targeted pushing effect on the clamp 8 are provided as well . this abutment edge 68 may also be referred to as a pushing edge or thrust lug . this is why it is provided with the reference symbol 69 . the tongue rests against a part of a clamp web 29 over the length designated with the reference line 70 . in this context , the insertion opening 63 also enables that the contact between the tongue 13 and the clamp 8 is maintained during the tilting of the clamp 8 . the tissue - protecting protrusion 61 with its protective function for animal or human tissue can be clearly deduced from fig3 . the guiding effect of the movement - guiding element 64 / deflector 65 / pilot bead 66 can be clearly taken from fig3 to 39 and 43 . here , it can also be clearly seen that the pilot bead 66 prevents the clamp 8 from getting caught . the movement - guiding element 64 also enhances the stiffness of the tongue 13 . in this way , a catching protection and an edge shielding function are provided in addition to an anti - bulging function . this is why the clamp 8 cannot get caught on a folded sheet metal portion of the tongue 13 . this may also be referred to as “ edge shielding ”. the tongue 13 is threaded through several clamps 8 without taking the function of guiding it . it is an elongated element with a high proneness of kinking in the course of advancing and guiding the most distal clip / the most distal clamp 8 , with smallest tolerances . a lengthwise flange 71 prevents the tongue 13 from buckling . longitudinal beads as shown in fig3 to 43 also have an anti - buckling effect . the point of the tongue 13 allows to reliably grasp the clamp 8 , and the transmission of forces onto the clamp 8 in the event of an angular or positional change is achieved just as the compensation of tolerances . implementing the tip as a flexible portion , for instance by using a material with smaller thickness , by the provision of elasticity holes , by means of cut - outs for reducing the bending forces , allows to achieve an advantageous embodiment . all those special lug or tip shapes are advantageous which prevent the thrust lugs 69 from getting levered out . the situation of the tongue 13 slipping off from a clamp web / leg 29 is effectively prevented in the manner described above . the tissue - protecting protrusion 61 protrudes beyond the sheet metal at the tip of the tongue and is in abutment on the inner side of a clamp 8 in the leg fillet provided there . it is to be noted that the deflector 65 / the pilot bead 66 has the same depth as the flange 71 of the tongue 13 , to prevent any thrust transmission to the clamp 8 . in the following fig4 to 51 , the spring support 42 is illustrated and explained in more detail . the spring support 42 comprises a holding catch / a cam 72 provided for being hooked into the retaining rail 12 in order to establish an axial and / or radial fixation . further , the spring support 42 comprises a cam / a lug 73 for immobilizing the spring support on the outer tube 8 . said cam 73 is surrounded by a sealing surface 74 . the latter serves for sealing off the recess in the outer tube 5 , so that no fluid can escape from the shaft - type instrument towards outside , and fluids from outside the shaft - type instrument 1 should not reach its interior either . the area which forms the sealing surface 74 is designed in the manner of a dome spring which is provided with the reference symbol 75 . thus , the wedge - shaped cam 73 lies within the sealing surface 74 of the dome spring 75 . this dome spring 75 gets caulked radially in one direction , because it is arranged so as to be off - center . the holding catch 72 and a recess accommodating it may be designed such that the respective fixations of the metal retaining plate 12 on the spring support 42 in radial and axial direction are effected separate from each other . in this case , the tolerances can be better used as if this was performed on a component in both directions . this is why a protrusion 76 is provided which is only designed for axially supporting the retaining rail 12 , whereas the holding catches 72 are designed for the radial fixation . thus , the spring support 42 has shell design having a positive effect on the elasticity . the spring support 42 serves for the fixation on the outer tube 5 . it may be implemented as an injection - molded part comprising a central feed - through for guiding the pusher rod / feed rod 19 . it may be designed in the manner of an integrated annular spring and comprise a springy , thin - walled oversize bulge . an extensive contact around the cam 73 , being configured in the manner of a retaining cam , is advantageous in terms of producing tightness . a protrusion / retaining cam having a centering effect engages in the outer tube 5 easier if it has chamfered edges . such chamfered edges may be provided on all protrusions or lugs . the spring support 42 is firmly clipped in place on the retaining rail 12 . thus , the spring support 42 comprises a through - hole 77 provided in the longitudinal direction and having the function of guiding the feed rod 19 . fig5 shows the state of the spring support 42 in the state when clipped in place in the metal retaining plate forming the retaining rail 12 . this situation is also illustrated in fig5 . the bridge / abutment plate 55 may also be referred to as an abutment plate . further , the retaining rail mounting hole 56 may be briefly referred to as a mounting hole .	0
according to one embodiment of this invention , a ruthenium complex photosens tizer dye is represented by the following general formula ( i ): where z 1 and z 2 individually represent hydrogen atom ( h ), lithium ( li ), sodium ( na ), or tetra - alkyl ammonium group represented by the following formula ( a ), where x 1 to x 4 individually represent c m h 2m + 1 ( m is an integer from 1 to 6 ), in formula ( i ), a is one of the followings : h , or c m h 2m + 1 ( m is an integer from 1 to 15 ), or ch 2 [ oc 2 h 4 ] p oc m h 2m + 1 ( p is an integer from 1 to 30 , m is an integer from 1 to 15 ); in the formulae ( 110 ) to ( 132 ), n is zero or an integer from 1 to 15 , in formula ( i ), b , c , and d are individually one of the followings : h , or c m h 2m + 1 ( m is an integer from 1 to 15 ), or ch 2 [ oc 2 h 4 ] p oc m h 2m + 1 ( p is an integer from 1 to 30 , m is an integer from 1 to 15 ); where r 3 , r 4 , r 7 , r 9 , r 10 , r 21 , r 22 , r 24 , r 26 , r 27 , and r 39 to r 43 represent c m h 2m + 1 ( m is zero or an integer from 1 to 15 ); r , r 12 to r 15 , r 19 , r 28 to r 33 , r 37 , and r 44 to r 48 represent c m h 2m + 1 ( m is an integer from 1 to 15 ); r 1 , r 11 , r 17 , and r 35 represent c m h 2m + 1 ( m is an integer from 1 to 15 ) or phenyl ; r 2 , r 16 , and r 34 represent ch 2 [ oc 2 h 4 ] p oc m h 2m + 1 ( p is an integer from 1 to 30 , m is an integer from 1 to 15 ); r 18 , r 20 , r 36 , and r 38 represent ch 2 [ oc 2 h 4 ] p oc m h 2m + 1 or c m h 2m + 1 ( p is an integer from 1 to 30 , m is an integer from 1 to 15 ). in formulae 123 , 125 , 147 , 148 , 150 , 170 , 172 , 173 and 175 , x represents se , s or o . in formulae 110 to 115 and 134 to 138 , x represents f , cl , br , i or c m h 2m + 1 ( m is an integer from 1 to 15 ). several exemplary embodiments will be described below to illustrate the processes of synthesis of the ruthenium complex photosensitizer dyes 1 , 2 and 3 of this invention . the structures of the ruthenium complex photosensitizer dyes 1 , 2 and 3 are showed below . it must be understood that the exemplary embodiments should be regarded as illustrative rather than restrictive . put 20 ml of polyphosphoric acid ( ppa ) into a double - necked flask , stir and preheat the solution to about 90 ° c . then , slowly add about 2 . 46 g ( about 0 . 02 mol ) of 2 - picolinic acid into the double - necked flask , and keep stirring the mixture evenly for about 30 minutes . afterwards add about 2 . 16 g ( about 0 . 02 mol ) of o - phenylenediamine , then raise temperature to about 150 ° c . and keep stirring evenly the mixture for about 4 hours . when the reaction ends , lower the temperature of the mixture to about 100 ° c . then , carefully and rapidly pour the reactant into iced water , and neutralize the mixture to weak alkalinity ( about ph 9 ) with 1m sodium hydroxide ( naoh ) solution . a pinkish purple color solid product is precipitated now . the solid is filtered out by suction , then it is dried by heat and purified by column chromatograph using a hexane / ethyl acetate ( ea ) solution ( 1 : 2 ) as eluent . about 2 . 21 g of white color solid is obtained with the yield of about 56 . 7 %. the white solid product is 2 -( pyridin - 2 - yl )- 1h - benzimidazole . mix about 0 . 195 g ( about 1 mmol ) of the white solid product obtained in step 1 , about 0 . 276 g ( about 2 mmol ) of k 2 co 3 , and about 15 ml of n , n ′- dimethylformamide ( dmf ) in a reaction vessel and keep stirring for about 10 minutes . then , carefully inject about 0 . 385 ml ( about 3 mmol ) of 2 , 4 - difluorobenzyl bromide into the mixture by a syringe and let the mixture react for about 3 hours at room temperature . when the reaction ends , pour the reactant into iced water and extract using ea . then collect and dehydrate the organic layer using anhydrous sodium sulfate . after filtration and concentration , a yellow color viscous liquid is obtained . then purify the yellow viscous liquid by column chromatograph using a hexane / ea solution ( 3 : 1 ) as eluent . then , dry it by vacuum suction and collect about 0 . 242 g of beige - white color solid ( i . e . the ligands l1 ) . the yield is about 75 . 3 %. the steps of synthesis of ruthenium complex photosensitizer dye 1 are shown below . ( 1 ) in the environment of dmf and argon ( ar ), two equivalents of the ligand l1 ( about 0 . 257 g , about 0 . 8 mmol ) are reacted with one equivalent of [ rucl 2 ( p - cymene )] 2 ( about 0 . 244 g , about 0 . 4 mmol ) at a temperature of about 70 ° c . for about 4 hours to form [ ru ( l1 )( p - cymene )] c1 coordination from broken dichloride - bridged structure . ( 2 ) then , add two equivalents of 4 , 4 ′- dicarboxy - 2 , 2 ′- bipyridine ( dcbpy , l ) ( about 0 . 195 g , about 0 . 8 mmol ) and raise the temperature to about 140 ° c . for reaction for about 4 hours , resulting in [ ru ( l )( l1 )( c1 ) 2 ]. ( 3 ) finally , add excess amount of potassium thiocyanate ( kscn ) and let the mixture react at about 140 ° c . for about 5 hours . after that , remove residual dmf from the reaction vessel using a distillation apparatus and kscn residuals by water ( h 2 o ) . after suction filtration , about 0 . 563 g of the ruthenium complex photosensitizer dye 1 is obtained . the yield is about 90 %. put 20 ml of polyphosphoric acid ( ppa ) into a double - necked flask , stir and preheat to about 90 ° c . then , slowly add about 2 . 00 g ( about 0 . 02 mol ) of 4 - bromopyridine - 2 - carboxylic into the flask , and keep stirring the mixture evenly for about 30 minutes . afterwards , add about 1 . 08 g ( about 0 . 01 mol ) of o - phenylenediamine and raise the temperature to about 150 ° c . and keep stirring the mixture evenly for about 4 hours . when the reaction ends , lower the temperature to about 100 ° c . then , carefully and rapidly pour the reactant into iced water , and neutralize it to weak alkalinity ( about ph 9 ) with 1m sodium hydroxide solution . a pinkish purple color solid product is precipitated . the solid product is filtered by suction and dried by heat , then purified by column chromatograph using a hexane / ea solution ( 1 : 3 ) as eluent . about 1 . 47 g of white color solid is obtained with the yield of about 53 . 8 %. the white solid product is 2 -( 4 - bromopyridine - 2 - yl )- 1h - benzimidazole . mix about 0 . 273 g ( about 1 mmol ) of the white solid product obtained in step 1 , about 0 . 276 g ( about 2 mmol ) of k 2 co 3 , and about 15 ml of dmf in a reaction vessel and stir for about 10 minutes . then , carefully inject about 0 . 385 ml ( about 3 mmol ) of 2 , 4 - difluorobenzyl bromide into the mixture by a syringe and keep at room temperature for about 3 hours . when the reaction ends , pour the reactant into iced water and extract using ea . collect the organic layer and dehydrate it using anhydrous sodium sulfate . after filtration and concentration , a yellow color viscous liquid is obtained . then purify the yellow viscous liquid by column chromatograph using a hexane / ea solution ( 2 : 1 ) as eluent . then , after vacuum suction , about 0 . 273 g of beige - white color solid is obtained with the yield of about 68 . 3 %. the beige - white solid product is 1 -( 2 , 4 - difluorobenzyl )- 2 -( 4 - bromopyridin - 2 - yl )- benzimidazole . mix about 0 . 24 g ( about 0 . 6 mmol ) of the beige - white solid product obtained in step 2 , about 0 . 092 g ( about 0 . 72 mmol ) of thiophen - 2 - yl - 2 - boronic acid , about 0 . 0462 g ( about 0 . 04 mmol ) of pd ( pph 3 ) 4 , and about 20 ml of tetrahydrofuran ( thf ) in a reaction vessel . in the environment of nitrogen gas , add about 2 ml of 2m k 2 co 3 , then the mixture is heated and refluxed for about 8 hours . when the reaction ends , pour the reactant into iced water and extracte using ch 2 cl 2 . collect and dehydrate the organic layer using anhydrous magnesium sulfate . after filtration and concentration , a light yellow color viscous liquid is obtained . purify the light yellow viscous liquid by column chromatograph using a hexane / ea solution ( 10 : 1 ) as eluent . then , about 0 . 22 g of beige - white color solid ( i . e . the ligands l2 ) is obtained with the yield of about 91 %. the steps of synthesis of ruthenium complex photosensitizer dye 2 are shown below . ( 1 ) in the environment of dmf and argon , two equivalents of the ligand l2 ( about 0 . 322 g , about 0 . 8 mmol ) are reacted with one equivalent of [ rucl 2 ( p - cymene )] 2 ( about 0 . 244 g , about 0 . 4 mmol ) at a temperature of about 70 ° c . for 4 hours to fog in [ ru ( l2 )( p - cymene )] cl coordination from broken dichloride - bridged structure . ( 2 ) then add two equivalents of 4 , 4 ′- dicarboxy - 2 , 2 ′- bipyridine ( dcbpy , l ) ( about 0 . 195 g , about 0 . 8 mmol ) and raise the temperature to about 140 ° c . for reaction for about 4 hours , resulting in [ ru ( l )( l2 )( c1 ) 2 ]. ( 3 ) finally , add excessive amount of potassium thiocyanate ( kscn ) into the mixture and let it react at about 140 ° c . for about 5 hours . after that , remove residual dmf in the reaction vessel using a distillation apparatus and kscn residuals using water . after suction filtration , about 0 . 612 g of ruthenium complex photosensitizer dye 2 is obtained with the yield of about 88 . 5 %. mix about 0 . 96 g ( about 0 . 03 mol ) of sulfur ( s ) powder , about 1 . 07 g ( about 0 . 01 mol ) of 2 , 4 - lutidine , and about 1 . 08 g ( about 0 . 01 mol ) of o - phenylenediamine in a single - necked flask . then , raise the reaction temperature to about 160 ° c . and keep stirring evenly for about 6 hours till the yellow brown liquid turn into yellow solid . finally , the reaction is terminated by addition of methanol . after filtering out the sulfur powder , the collected liquid is evaporated by a rotary concentrator . about 1 . 3 g of light yellow color solid is obtained with the yield of about 62 . 2 %. the light yellow solid is 2 -( 4 - methylpyridin - 2 - yl ) benzimidazole . mix about 0 . 209 g ( about 1 mmol ) of the light yellow solid product obtained in step 1 , about 0 . 276 g ( about 2 mmol ) of k 2 co 3 , and about 15 ml of dmf in a reaction vessel and keep stirring for about 10 minutes . then , carefully inject about 0 . 385 ml ( about 3 mmol ) of 2 , 4 - difluorobenzyl bromide into the mixture by a syringe , and let it react for about 3 hours at room temperature . when the reaction ends , pour the mixture into iced water then extracte using ea . collect and dehydrate the organic layer using anhydrous sodium sulfate . after filtration and concentration , a yellow color viscous liquid is obtained . purify the yellow viscous liquid by column chromatograph using a hexane / ea solution ( 4 : 1 ) as eluent . then , after vacuum suction , about 0 . 23 g of beige - white color solid is obtained with the yield of about 68 . 7 %. the beige - white solid product is 1 -( 2 , 4 - difluorobenzyl )- 2 -( 4 - methylpyridin - 2 - yl ) benzimidazole . put about 0 . 335 g ( about 0 . 001 mmol ) of the beige - white solid product obtained in step 2 in a 100 ml double - necked flask . then , the flask is alternately evacuated then filled with nitrogen gas for three times . after that , add 10 ml of anhydrous thf into the flask . then slowly add 2m lithium diisopropylamide ( lda , about 0 . 0012 mol , about 0 . 6 ml ) at a temperature of − 20 ° c . keep stirring the mixture for about 30 minutes at above temperature . add about 0 . 17 g ( about 0 . 0015 mol ) of thiophene - 2 - carbaldehyde dissolved in anhydrous thf into the flask . keep stirring the mixture for about 10 minutes at above temperature then move to room temperature for reaction for about 2 hours . the reaction is terminated by addition of methanol ( meoh ). next , after thf is removed , the residue was extracted three times using ch 2 cl 2 . collect and dehydrate the organic layer using anhydrous magnesium sulfate . after filtration and concentration , about 0 . 172 g of light yellow color viscous liquid is obtained . place the light yellow viscous liquid in a 100 ml single - necked flask then add about 10 ml of pyridine . under ice bath condition , add poc1 3 ( about 0 . 0012 mol / 0 . 11 ml ). then put the mixture in room temperature for reaction for about 10 minutes . terminate the reaction by adding meoh . next , after pyridine was removed , the residue was extracted three times using ch 2 cl 2 ( about 10 ml ) and saline water . collect and dehydrate the organic layer using anhydrous magnesium sulfate . then , after vacuum suction , a yellow color liquid is obtained . purify the yellow liquid by column chromatograph using a hexane / ea solution ( 2 : 1 ) as eluent . about 0 . 17 g of beige - white color solid ( i . e . the ligands l3 ) is obtained with the yield of about 39 . 6 %. the steps of synthesis of ruthenium complex photosensitizer dye 3 are shown below . ( 1 ) in the environment of dmf and argon , two equivalents of the ligand l3 ( about 0 . 343 g , about 0 . 8 mmol ) is reacted with one equivalent of [ rucl 2 ( p - cymene )] 2 ( about 0 . 244 g , about 0 . 4 mmol ) at a temperature of about 70 ° c . for about 4 hours to form [ ru ( l3 )( p - cymene )] cl coordination . from the broken dichloride - bridged structure . ( 2 ) then add two equivalents of 4 , 4 ′- dicarboxy - 2 , 2 ′- bipyridine ( dcbpy , l ) ( about 0 . 195 g , about 0 . 8 mmol ) to the mixture and raise the temperature to 140 ° c . for reaction for about 4 hours , resulting in [ ru ( l )( l3 )( cl ) 2 ]. ( 3 ) finally , add excessive amount of kscn to the mixture and let react at about 140 ° c . for about 5 hours . after that , remove residual dmf in the reaction vessel using a distillation apparatus and residuals of kscn using water . after suction filtration , about 0 . 586 g of ruthenium complex photosensitizer dye 3 is obtained with the yield of about 82 . 3 %. fig1 shows the comparison of uv - visible spectra of ruthenium complex photosensitizer dyes 1 , 2 and 3 of this invention and conventional n719 dye . fig2 shows the comparison of iv curves of the ruthenium complex photosensitizer dyes 1 , 2 and 3 of this invention and conventional n719 dye . table 1 shows the comparison of photoelectric conversion efficiency of solar cell devices employing above - mentioned ruthenium complex photosensitizer dyes 1 , 2 and 3 and conventional n719 dye . as shown the efficiency of the ruthenium complex photosensitizer dyes 1 , 2 and 3 are better than that of the conventional n719 dye . the photoelectric conversion efficiency ( η ) is obtained by the equation below , η = p m ⁢ ⁢ p p i ⁢ ⁢ n = j m ⁢ ⁢ p ⁢ * v m ⁢ ⁢ p ⁢ p i ⁢ ⁢ n = j sc * v oc * ff p i ⁢ ⁢ n where p in is the input radiation power , and p mp is the maximum output power (= j mp × v mp ), and ff stands for the fill factor defined as ff = j m ⁢ ⁢ p * v m ⁢ ⁢ p j sc * v oc where l sc is the short circuit current , and v ∞ is the open circuit voltage . since the ruthenium complex photosensitizer dyes of this invention have smaller molecular structures than the conventional n719 photosensitizer dye , they can be adsorbed , in greater amount , on thin titanium dioxide photoanodes of solar cells , leading to larger photoelectric current . therefore , the layers of the titanium dioxide photoanodes can be reduced thus simplifying the processes and lowering the cost of manufacturing of the elements . since the dye - sensitized solar cells employing the ruthenium complex photosensitizer dyes of this invention have higher photocurrent density than those using conventional n719 photosensitizer dye , the former has superior overall solar elements efficiency than the latter . although some embodiments of this invention are described in details above , it is intended that the scope of this invention may not be limited by the descriptions above , but rather by the claims appended hereto . also , it is intended that the following appended claims be interpreted as that all possible alterations , pemiutations , and equivalents fall within the true spirit and scope of this invention .	8
fig1 shows , in simplified block diagram form , details of an interactive system in which the invention may be advantageously employed . it should be noted that the arrangement shown in fig1 is but one example of an application of the invention . indeed , a plurality of different user interfaces and / or one more identical user interfaces may be employed as desired . specifically , shown in fig1 is sisl ( several interfaces , single logic ) service unit 101 ; home / office computer 102 used as a customer and / or provider interface , including automatic speech recognition having a natural language understanding , if desired , that is interfaced to sisl service unit 101 via an internet link 103 ; telephone 104 also used as a customer and / or provider interface that is interfaced to sisl service unit 101 via a telephone network 105 including , for example , touch - tone , i . e ., multi - frequency signaling ; computer 106 used as a customer and / or provider interface , which may also have automatic speech recognition including natural language understanding , that is interfaced to sisl service unit 101 via a local area network ( lan ); and atm ( automatic teller machine ) used as a customer interface and , typically , is interfaced to sisl service unit 101 via a direct connect 109 . a key advantage of sisl is that all user interfaces to a service share the same single service logic . sisl provides a clean separation between the service logic and the software for a variety of user interfaces including but not limited to java applets , html pages , speech - based natural language dialog , and telephone - based voice access . in this example , sisl is implemented using the java programming language . at the outset it is felt best to describe some of the principles employed in implementing the flexible interactive service including an embodiment of the invention . for simplicity and clarity of exposition , these principles will be presented in the context of a so - called any - time teller banking service employing the invention . the any - time teller is an interactive banking service . the service is login protected ; customers must authenticate themselves by entering an identifier ( login ) and pin , i . e ., personal identification number , ( password ) to access the functions . as customers may have many money accounts , most functions require the customer to select the account ( s ) involved . once authenticated , the customer may : make a withdrawal . the service makes sure the customer has enough money in the account , then withdraws the specified amount . transfer funds between accounts . the service prompts the customer to select a source and target account , and a transfer amount , and performs the transfer if ( 1 ) the customer has enough money in the source account , and ( 2 ) transfers are permitted between the two accounts . get the balance of an account . display the balance with respect to all posted transactions . the transfer capability of the any - time teller requires the collection of three events : the source account ( src ), target account ( tgt ), and dollar amount ( amt ). there are five constraints that those input events must meet before a transfer can take place : c 4 : amt must be less than or equal to the balance of src c 5 : the bank must allow transfers from src to tgt the service should check whether or not a constraint is violated as soon as possible ; hence , it must be prepared to react when only a subset of the three events is present . the service must then prompt for the remaining events . some basic principles are now considered related to the design and implementation of interactive services with multiple and varied user interfaces . these principles are especially important in the presence of multiple interfaces including those based on spoken natural language . the source account , target account , and dollar amount of the transfer capability should be independent events that can be collected in any order , where all three events are necessary to perform a transfer . by making explicit independent and dependent events , it in clear what events may be reordered without affecting the behavior of the service . this points the way to our first principle of the service specification : principle 1 : specify the service logic as a set of constraints on events and introduce a constraint between two events only when absolutely necessary for the correct functioning of a service . that is , the service logic should be able to accept independent input events in different orders . it is often desirable for a service to respond as soon as possible with error conditions about user input . since a constraint on the input events may refer to any arbitrary subset of those events , it is desirable that the service logic should be able to accept arbitrary subsets of events at any time . principle 2 : the service logic should accept an incomplete input , i . e ., subsets of the universe of possible events . unfortunately , humans often change their mind and / or make mistakes . whenever possible , services must accommodate these shortcomings of our species , providing a capability to correct information or back out of a transaction . this leads to our third principle : principle 3 : the service logic should allow the user to back up to correct or update previously submitted information at any time . principle 4 : the service logic should allow the user to back up to previous points in the service . services that obey the above principles generalize from linear user interactions to potentially allow multiple points of interaction to be enabled at a given instant . this information serves as an abstraction of the current control point of the service , and can be handled in a different manner by different user interfaces . for example , in automatic speech recognition interfaces , the information about currently enabled events is used by the user interface in two ways : to appropriately prompt the user for information , thus compensating for the lack of visual cues ; and a user interface need not respond to all currently enabled events of the service . thus , different user interfaces can formulate different queries to the user even though the control point in the underlying service logic , as revealed by the current set of enabled events , is the same . the decoupling that we are seeking between the user interface and the service logic , therefore points the way to our last principle of the service specification : principle 5 : at any point in the service , the service logic must automatically report to the user interfaces all currently enabled events , user prompts , help , and ways to revert back to previous points in the service . user interfaces have two main responsibilities with respect to the sisl architecture that reflect the two - way information flow between the user interface and service logic : based on the events received from the service logic , via the service monitor , prompt the user to provide the appropriate information and respond if the user requests help . collect the information from the user and transform the information into events to be sent to the service logic , via the service monitor . indeed , any user interface ( ui ) that performs these functions can be employed in conjunction with a sisl service logic . additionally , sisl provides a convenient framework for designing and implementing web - based , applet - based , automatic speech recognition - based and telephone voice - based interfaces . to implement such user interfaces , the ui designer need only specify two functions corresponding to the prompt and help mechanism . for automatic speech recognition interfaces , a set of speech grammars , i . e ., the input to a speech recognition engine that permits it to efficiently and effectively recognize spoken input , together with a third function that specifies which grammars to enable is also required . a prompt function that generates the string to be given as the prompt to the user . an example , in pseudo code form is shown in fig6 . the sisl infrastructure automatically causes automatic speech recognition - based interfaces to speak the prompt string . web - based interfaces automatically display the prompt string , as well as , radio buttons corresponding to the possible transaction choices . for the other prompt events , text fields are automatically displayed , while submit buttons are automatically displayed for enabled events that allow the user to return to earlier points in the service . screen snapshots are shown in fig7 and 8 . specifically , fig7 is a pictorial representation of a web page used in the web interface for a choice node , and fig8 is a pictorial representation of a web page used in the web interface for a constraint node . a help function that generates the string to be given as the prompt to the user . an example , in pseudo code form is also shown in fig6 . a grammar function that enables the correct set of grammar rules ; this function is only needed for automatic speech recognition - based interfaces . an example , in pseudo code form is shown in fig9 . as indicated , fig6 shows , in pseudo code form , portions of the prompt and help functions shared by an automatic speech recognition - based interface , web - based interface and telephone - based voice interface for the any - time teller banking service . portions of the grammar rules , against which the automatic speech recognition engine will parse spoken input from the user , are shown in fig9 . again , fig1 illustrates a portion of the associated grammar function shared by an automatic speech recognition - based interface and a telephone - based voice interface . from these functions and grammars , the sisl infrastructure automatically coordinates the collection and event transformation mechanisms , and integrates the user interface with the service logic and the service monitor . for automatic speech recognition - based interfaces , the sisl infrastructure automatically generates a desktop interface based on java speech api ( application programming interface ). to enable telephone - based voice access to the service , sisl automatically generates voxml pages , which specify the voice dialog to be carried out on a telephony platform . for web - based interfaces , the sisl infrastructure automatically generates html ( hypertext markup language ) pages . it is noted that sisl provides a mechanism for the ui designer to customize the look and feel of the interface . fig2 shows , in simplified block form , details of the sisl ( several interfaces , single logic ) architecture employed in the embodiment of fig1 . the sisl architecture together with the event communication protocol provides modularity between the service logic 201 and user interfaces 204 . in particular , two features of the event communication protocol allow service logic 201 to function completely without knowledge of the specifics of the individual user interfaces 204 . these features are : ( 1 ) events are multicast from service logic 201 via service monitor 202 to user interfaces 204 and , consequently , service logic 201 does not need to know the destinations of these events ; and ( 2 ) the source of the events from the user interfaces 204 is not recorded and , consequently , the service logic 201 does not know which one or more of user interfaces 204 sent the events . service monitor 202 is responsible for maintaining this communication protocol . this modularity allows service providers to provide interchangeable user interfaces 204 , or add new ones , to a single consistent source of service logic and data . specifically , shown in fig2 are service logic unit 201 , service monitor 202 and user interfaces 204 - 1 through 204 - n . the key principle underlying sisl is that all user interfaces 204 to a service share a single service logic 201 . all communications between the service logic 201 and its multiple user interfaces 204 are through events , via a service monitor 202 . events from the service logic 201 are broadcast to the user interfaces 204 via 203 to the service monitor 202 and , then , via 205 as a set of enabled events to the user interfaces 204 . at the outset of the service , for example the any - time teller banking service , each user interface 204 registers with the service monitor 202 to indicate which events it is interested in receiving . after collecting information from the user , the user interfaces 204 send events to the service monitor 202 via bi - directional links 205 ; the service monitor 202 does not record the source of these events . the service monitor 202 passes the events , one at a time , via 203 to the service logic 201 . details of a service monitor , which can be advantageously employed for service monitor 202 , are described in co - pending u . s . patent application ser . no . 09 / 386 , 093 ( t . j . ball et al .) filed concurrently herewith and assigned to the assignee of this application . event communication supports decoupling of the service logic 201 and the user interfaces 204 , and allows service providers to provide interchangeable user interfaces 204 , or add new ones , to a single consistent source of service logic 201 and data . in each round of interaction , the sisl infrastructure automatically sends out a set of events via 203 from the service logic 201 to the service monitor 202 , corresponding to the events that are currently enabled in the service logic 201 . there are three kinds of events : prompt events , up events , and notify events . prompt events indicate to the user interface what information to communicate to the user and what information the service is ready to accept . there are three kinds of prompt events : prompt_choice events are disjunctive choices currently enabled in the service logic 201 . for example , after the user has successfully logged into the any - time teller banking service , a choice among the different transaction types is enabled . the service logic 201 sends a prompt_choice_deposit , prompt_choice_withdrawal event , and a prompt_choice_transfer event , and so forth , via 203 to the service monitor 202 . prompt_req events are the events currently required by the service logic 201 . for example , suppose the user has chosen to perform a transfer transaction . the any - time teller requires that the user input a source account , a transfer account , and amount , and hence sends prompt_req_src , prompt_req_tgt , and prompt_req_amt events via 203 to the service monitor 202 . prompt_opt events are events enabled in the service logic 201 , for which the user may correct previously given information . for example , suppose the user is performing a transfer and has already provided his / her source and target accounts , but not the amount . the service logic 201 sends prompt_opt_src , prompt_opt_tgt , and prompt_req_amt events via 203 to the service monitor 202 . this indicates that the user may override the previously given source and target accounts with new information . up events correspond to prior points in the service logic 201 to which the user may go back . for example , the service logic 201 sends an up_mainmenu event via 203 to the service monitor 202 . this allows the user to abort any transaction and go back up to the main menu . notify events are simply notifications that the user interface 204 should give the user ; for example , that a transaction has completed successfully or that information provided by the user was incorrect or inconsistent . fig3 is a flowchart illustrating the steps in implementing the sisl architecture of fig2 . specifically , the implementation process is started via step 301 . then , step 302 causes the sisl logic to be written in sisl . step 303 causes the service monitor 202 to be written . thereafter , a plurality of user interfaces ui - 1 thorough ui - n are developed in steps 304 - 1 through 304 - n . fig4 is a flowchart illustrating the steps in the process of executing reactive constraint graphs . specifically , step 401 obtains a root node ( n ). then step 402 tests to determine if the obtained node is a data based choice node . if the test result in step 402 is no , step 403 tests to determine whether the obtained node is an event based choice node . if the tests result in step 403 is no , step 404 tests to determine if the obtained node is an action node . if the test result in step 404 is yes , step 405 causes the execution of the action , the execution of the notification associated with node “ n ” and sets “ n = child node ”, as determined from the current obtained node . if the test result in step 404 is no , step 406 causes the execution of the process of the constraint flowchart of fig5 as described below , until a new child node is determined and , then , assigns “ n ” to the determined new child node . returning to step 402 , if the test result is yes , the node is data based , and step 407 causes a unique arc “ a ” to be selected from node “ n ” whose precondition is true . then step 408 causes the execution of an action and notification associated with arc “ a ”. thereafter , step 408 sets “ n = child ” node of “ a ”. returning to step 403 , if the test result is yes , the node is event based , and step 409 causes a wait for any event “ e ” that is the label of some arc “ a ” from node “ n ” or is the uplabel of some ancestor node of node “ n ”. then , step 410 tests to determine if event “ e ” is the uplabel of some ancestor node of node “ n ”. if the test result in step 410 is yes , step 411 causes control to be transferred to the ancestor node . if the test result in step 410 is no , control is passed to step 408 , which is then effected as described above . reactive constraints are discussed further below . fig5 a and fig5 b when connected a — a , b — b , c — c , and d — d is a flowchart illustrating the steps in the process of executing constraint nodes . specifically , step 501 causes the entry action to be executed . then , step 502 causes initialization of a table to be one entry for each event occurring in an associated constraint ; value to false ; and data to empty . thereafter , step 503 causes a prompt_req to be sent to service monitor 202 for every event “ e ” whose value is set to false in the table , and a prompt_opt to be sent to service monitor 202 for every event “ e ” whose value is set to true in the table . step 504 waits for an event “ e ” that occurs in any associated constraint , or is the uplabel of an ancestor node . then , step 505 tests to determine whether event “ e ” is an uplabel of an ancestor node . if the test result instep 505 is yes , control is transferred to the ancestor node via step 506 . if the test result in step 505 is no , step 507 causes event “ e ” to be set true in the table , and assigns data to be “ e &# 39 ; s ” data . then , step 508 tests to determine if any constraints are enabled . if the test result in step 508 is yes , step 509 causes the next enabled constraint to be evaluated . then , step 510 tests to determine whether the evaluated constraint has been satisfied . if the test result in step 510 is no , the constraint is not satisfied and step 511 causes the execution to be effected of the violation action and the notification of violated constraint . step 512 causes the setting of event “ e ” to be false in the table and clears “ e &# 39 ; s ” data . thereafter , step 513 tests to determine if a child node is specified . if the test result instep 513 is yes , step 514 causes control to be transferred to the specified child node . returning to step 508 , if the test result is no , there are no remaining constraints that are enabled and step 515 causes the execution of the satisfaction action and the notification of all satisfied constraints . then , step 516 tests to determine whether all constraints have been satisfied . if the test result in step 516 is yes , step 517 causes the child node to be determined and , then , transfers control to it . if the test result in step 516 is no , control is returned to step 503 and appropriate ones of steps 503 through 517 are iterated until either step 506 is reached , or step 514 is reached , or step 517 is reached . returning to step 510 , if a yes result is obtained , control is returned to step 508 and steps 508 through 510 are iterated until either step 508 yields a no result or step 510 yields a no result . then , the processes , as described above regarding steps 508 or 510 yielding a no result are repeated . returning to step 513 , if the test result is no , the child node is not specified and control is returned to step 503 . thereafter , appropriate ones of steps 503 through 517 are iterated until either step 506 , or step 514 or step 517 is reached . fig6 . illustrates in pseudo code form a portion of an automatic speech recognition ( asr ) interface and a web user interface employed in the any - time teller example . the pseudo code of fig6 is self explanatory and is as follows : if ( transaction_type . equals (“ transfer ”)){ if ( req_events . contains ({“ src ”, “ tgt ”, “ amount ”})){ return (“ please specify the source account , target account , and the amount you would like to transfer .”) if ( req_events . contains_any_of (“ startdeposit ”, “ startwithdrawal ”, “ starttransfer ”, “ startbalance ”){ return (“ you may make a deposit , withdrawal or transfer . or you may quit the service ”); fig9 shows in pseudo code form a portion of the asr interface grammar used in the any - time teller example . the pseudo code of fig9 is self explanatory and is as follows : fig1 shows in pseudo code form a portion of an asr user interface employed in the any - time teller example . the pseudo code of fig1 is self explanatory and is as follows : fig1 is a flow diagram illustrating a reactive constraint graph for a portion of the any - time teller banking service example . in sisl , the service logic 201 ( fig2 ) of an application is specified as a reactive constraint graph , which is a directed acyclic graph with an enriched structure on the nodes . the traversal of reactive constraint graphs is driven by the reception of events from the environment ; these events have an associated label , i . e ., the event name , and may carry associated data . in response , the graph traverses its nodes and executes actions ; the reaction of the graph ends when it needs to wait for the next event to be sent by the environment . for example , fig1 shows a sisl reactive constraint graph that implements part of the functionality of the any - time teller . reactive constraint graphs can have three kinds of nodes , namely , choice nodes , constraint nodes and action nodes . these nodes represent a disjunction of information to be received from the user . every choice node has a specified set of events . there are two forms of choice nodes , namely , event - based and data - based . every event - based choice node has a specified set of events . for every event in this set , the sisl infrastructure automatically sends out a corresponding prompt_choice event from the service logic 201 to the user interface , via the service monitor 202 . the choice node waits for the user interface to send , via the service monitor 202 , any event in the specified set . when such an event arrives , the corresponding transition is taken , and control transfers to the descendent , i . e ., child , node . for example , if a starttransfer event arrives when control is at the choice node , the corresponding transition is taken and control is transferred to the target constraint node . to ensure determinism , all outgoing transitions of a choice node must be labeled with distinct event names . every data - based choice node has a specified set of preconditions on data . to ensure determinism , these preconditions must be specified so that exactly one of them is “ true ” in any state of the system . when control reaches a data - based choice node , the transition associated with the unique “ true ” precondition is taken , and control is transferred to the child node . the constraint nodes represent a conjunction of information to be received from the user . every constraint node has an associated set of constraints on events . constraints have the following components : the evaluation function is a boolean function on the events in the signature . the optional satisfaction tuple consists of an optional action , not involving user interaction , and an optional notify function that may return a notify event with an associated message . if the constraint evaluates to true , the action is executed , the notify function is executed and the returned notify event is sent to the user interface via the service monitor 202 . the optional violation tuple consists of an optional action , not involving user interaction , an optional notify function that may return a notify event with an associated message , an optional uplabel function that may return the uplabel of an ancestor node and an optional child node . if the constraint evaluates to “ false ”, the action is executed , the notify function is executed and the returned notify event is sent to the user interfaces 204 via the service monitor 202 . the uplabel function is also executed ; if it returns an ancestor &# 39 ; s uplabel , it is generated , and hence control reverts back to the ancestor node . if no ancestor node &# 39 ; s uplabel is returned and a child node is specified , control is transferred to the specified child node . for example , amt & lt ;= balance ( src ) of 1107 in fig1 is equivalent to ? amt & lt ;= balance (? src ) in fig1 a and 12b , and is the evaluation of constraint ( c 4 ) of fig1 a and 12b , as described below . the signature of this constraint is the set { amt , src }, and the satisfaction notify function and violation notify function , respectively , report to the user whether or not the source account has enough funds to cover the requested amount . the notification ? eventname refers to the data on the event with name eventname . an associated set of constraints . in the current semantics and implementation , this set is totally ordered , specifying the priority order in which the constraints are evaluated . an optional finished tuple , consisting of an optional exit action , not involving user action , an optional notify function , an optional uplabel function and an optional child node . a detailed description of constraint node execution is shown in fig1 a and 13b and summarized below . the sisl infrastructure automatically sends out a prompt_req event , from the service logic 201 ( fig2 ) to the user interfaces 204 via the service monitor 202 , for every event that is still needed in order to evaluate some constraint . additionally , the constraint node sends out a prompt_opt event for all other events mentioned in the constraints . these correspond to the information that can be corrected by the user . in every round of interaction , the constraint node waits for the user interface to send , via the service monitor 202 , any event that is mentioned in the signature of its associated constraints . each constraint associated with a constraint node is evaluated as soon as all of its events have arrived . if an event is resent by the user interfaces 204 , i . e ., information is corrected , all constraints with that event in their signature are re - evaluated . for every evaluated constraint , its optional satisfied / violated action is automatically executed , and a notify event is automatically sent to the user interfaces 204 , with the specified message . specifically , the constraints are evaluated in the specified priority order , currently the total ordered set . if any constraint is violated , the last received event is automatically erased from all constraints , since it caused an inconsistency . furthermore , the violation action is executed , the notify function is executed and the returned notify event is automatically sent to the user interfaces 204 via the service monitor 202 . the uplabel function is also executed ; if it returns an ancestor &# 39 ; s uplabel , it is generated and , hence control reverts back to that ancestor . for example , in fig1 , the constraint node 1103 for the transfer capability checks whether the source account is an active account of the given customer , i . e ., user , via constraint ( c 0 ) of fig1 . if not , it generates the uplabel “ loginmenu ”, and control is transferred back to the login node 1101 . then , the user must re - enter his / her login . if no ancestor node &# 39 ; s uplabel is returned and a child node is specified , control is transferred to that child node . for example , in fig1 , the login node 1101 checks whether the login is of a customer in good standing , via constraint good_customer of fig1 , which evaluates goodcustomer ( login ). if not , control is transferred to the quit node and the service is terminated . if no ancestor node &# 39 ; s uplabel is returned or child node specified for the violated constraint , the node reverts to waiting for events to arrive . if no constraints have been violated , the action of every satisfied constraint is executed , the associated notify functions are executed and the returned notify events are sent to the user interfaces 204 via the service monitor 202 . when all the constraints have been evaluated and are satisfied , the exit action and notify function associated with the constraint node are executed and the returned notify event is sent to the user interfaces 204 via the service monitor 202 . the uplabel function is also executed ; if it returns an ancestor node &# 39 ; s uplabel , it is generated , and hence control is returned back to the ancestor node . if no ancestor node &# 39 ; s uplabel is returned and a child node it specified , control is transferred to that child node . these nodes represent some action , not involving user interaction , to be taken . after the action is executed , control transfers to the child node . nodes can have an optional “ uplabel ”, which is used to transfer control from some child node back up to the node , allowing the user to revert back to previous points in the service . in each round of interaction , the sisl infrastructure automatically sends out an up event , from the service logic 201 to the user interfaces 204 via the service monitor 202 , corresponding to the uplabel of every ancestor of the current node . nodes can also have a self - looping arc , with a boolean precondition on data . this indicates that the subgraph from the node will be repeatedly executed until the precondition becomes false . by way of an example execution of the any - time teller banking service as shown in fig1 , the sisl based invention shall be illustrated using the web - based , automatic speech recognition - based and telephone voice - based user interfaces 204 partially set forth in pseudo code in fig6 and 10 , respectively . the service initially causes the statement “ welcome to any - time teller ” to be spoken . the control point is at the root node , which is a constraint node . for the constraint of the root node to be satisfied , the login and pin values must be identified , i . e ., login == pin , as shown in step 1101 of fig1 . the sisl infrastructure automatically sends out a prompt_req_login and a prompt_req_pin from the service logic 201 to the user interfaces 204 , via the service monitor 202 . the user interfaces 204 , via the prompt function , respond by saying “ please specify your login and personal identification number ”. for the web - based user interface , text fields for the login and pin are automatically generated , in known fashion ; for the speech recognition - based user interface , the grammars specified in the grammar function are automatically enabled . in this example , suppose that the user states “ my login is mary smith and my pin is mary smith ”, and hence a login event with the value “ mary smith ” and a pin event with the value “ mary smith ” are sent to the service logic 201 . since the login and pin are identical , the constraint is satisfied . the sisl infrastructure automatically sends out a notify event with the message “ hello mary smith ”. welcome to the sisl any - time teller ”. the user interface makes this statement to the user . control now proceeds to step 1102 and to the choice node . the sisl infrastructure automatically sends out : events from the service logic 201 ( fig2 ) to the user interfaces 204 , via the service monitor 202 , corresponding to the enabled choices . the user interfaces 204 ask the user “ what transaction would you like to do ?” fig7 shows a screen snapshot of the web - based user interface ; the possible choices are shown as radial buttons . for an automatic speech recognition - based user interface , if the user states “ i need help ”, the user interface states , via the help function shown in pseudo code form in fig6 “ you can make a withdrawal , deposit transfer or you can quit the service ”. consider that the user now chooses to perform a transfer , the starttransfer event is sent to the service logic 201 . control now proceeds to constraint node 1106 . the sisl infrastructure automatically sends out : events from the service logic 201 to the user interfaces 204 , via the service monitor 202 , together with a up_mainmenu event , since it is the uplabel of an ancestor node . assume that the user respond with “ i would like to transfer one thousand dollars ($ 1 , 000 . 00 ) from my checking account ”, or equivalently “ from checking , i would like to transfer one thousand dollars ($ 1 , 000 . 00 )”. either order of the transfer request information is allowed ; furthermore , this information in partial , since the target account is not specified . the user interface 204 sends a src event and an amt event , with the corresponding data , to the service monitor 202 , which sends them one at a time to the service logic 201 . assume that the src event is sent first , followed by the amt event . the constraints amt & gt ; o , isvalid ( src ) and amt & lt ;= balance ( src ) are automatically evaluated . assume that the checking account does not have a balance of at least $ 1 , 000 . 00 ; hence , there is a constraint violation and the supplied information is erased , since it was sent last . note that constraints are evaluated as soon as possible ; for example , the user is not required to specify a target account in order for the balance on the source account to be checked . the sisl infrastructure then automatically sends out a prompt_opt_src , prompt_req_tgt , prompt_req_amt and upmainmemu events from the service logic 201 to the user interfaces 204 , via the service monitor 202 , as well as , a notify event with the message “ your checking account does not have sufficient funds to cover the amount of $ 1 , 000 . 00 . please specify an amount and a target account .” the user interface 204 then notifies the user with this message and prompts the user for the information . assume now that the user states “ transfer five hundred dollars ($ 500 . 00 ) to savings ”. the amt and tgt events are sent to the service monitor 202 , and passed to the service logic 201 . the constraints are now all evaluated and satisfied , the service logic 201 automatically sends a notify event to the user interfaces 204 with the message “ your transfer of $ 500 . 00 from checking to savings was successful ”. control then is returned back up to the choice node 1102 ; the loop on the incoming arc to the choice node indicates that the corresponding subgraph is repeatedly executed until the condition on the arc becomes false . if the user wants to quit the service , the userquit event is sent to the service logic 201 , the hasquit variable is set to true , and the loop is terminated . while in step 1102 , a loop step 1104 is performed to test if the user has terminated , i . e ., quit , the session . if the user would like to abort at any time during a withdrawal , deposit or transfer transaction , he / she can state “ i would like to go back up to the main menu ”, which results in an up_mainmenu event to be sent to the service logic 201 . this causes control to be returned to the choice node 1102 , which has an associated upmainmenu label . if a user wishes to make a deposit control proceeds to the deposit constraint node 1106 . the sisl infrastructure automatically sends out events from the service logic 201 to the user interfaces 204 via service monitor 202 . if the target account is valid and the amount is greater than zero ( 0 ) the deposit is made and the associated notification is executed . if a user wishes to make a withdrawal control proceeds to the deposit constraint node 1107 . the sisl infrastructure automatically sends out : events from the service logic 201 to the user interfaces 204 via service monitor 202 . if the source account is valid and the amount is greater than zero ( 0 ), it is determined if amt & lt ;= balance ( src ) and , if so , the withdrawal is made and the associated notification is executed . fig1 a and fig1 b , when connected x — x , illustrate in pseudo code form the steps of a portion of the sisl service unit process used in the any - time teller banking service example . the pseudo code of fig1 a and 12b is self explanatory and is as follows : violation : notify (“ sorry , this account is not active . please log into the service again .”); violation : notify (“ sorry , your ”? src +“ account does not have sufficient funds to cover the amount of ”+? amt +“ dollars .”)); transfer = constraintnode ( constraints : { c 0 , c 1 , c 2 , c 3 , c 4 , c 5 }; fig1 a and fig1 b , when connected y — y , illustrate the steps performed in the execution of constraint nodes . the procedure of a constraint node is as follows : 1 . the node first executes its ( optional ) entry action . it then creates a table in which every event in the signature of a constraint associated with the node has a slot . each such event has a single slot in the table , even if it occurs in multiple constraints . each slot in the table contains three fields : the name of the event , the data associated with the event when it arrives , and a boolean variable that indicates whether the event arrived from the environment and did not cause a constraint violation . the data field of every slot is initially empty and the boolean variable in every slot is initially false . 2 . the node sends a prompt_req event to the user interfaces ( via the service monitor )— for every event “ e ” whose boolean variable is set to false in the table . 3 . the node sends a prompt_opt event to the user interfaces ( via the service monitor )— for every event “ e ” whose boolean variable is set to true in the table . 4 . the node then waits for any event that is in the signature of any constraint associated with the node , i . e ., has a slot in the table or is the uplabel of any ancestor node . 5 . upon arrival of any such event “ e ”, if “ e ” is the uplabel of some ancestor node , control is transferred to that ancestor . otherwise : ( a ) the boolean variable in the slot for “ e ” is set to true . the data associated with the event “ e ” is written in the table ; if previous data is present , it is first erased . ( b ) the enabled constraints “ c ” are those that satisfy the following conditions : all events in the signature of the constraint “ c ” have their boolean variables set to true in the table . ( c ) the enabled constraints “ c ” are evaluated in the specified priority order : its ( optional ) violation action and notify function are executed , and the returned notify event is sent to the user interfaces via the service monitor . the boolean variable in the slot for “ e ” is reset to false , and the data field is reinitialized to be empty . the uplabel function of constraint “ c ” is executed ( if it is specified ). if it returns the uplabel of an ancestor node , the uplabel is generated and control is transferred to the ancestor node . else the constraint node goes back to waiting for events , ( step 2 ). else the next enabled constraint is evaluated . if none remain to be evaluated , the constraint node goes to step5 ( d ). the ( optional ) satisfaction action and notify function of each satisfied constraint are executed , and the returned notify events are sent to the user interface via the service monitor . if all constraints associated with the node were enabled and satisfied . the ( optional ) exit action and notify function are executed and the returned notify event is sent to the user interfaces via the service monitor . the uplabel function of the constraint node is executed ( if it is specified ). if it returns the uplabel of an ancestor node , the uplabel is generated and control is transferred to the ancestor node . else the constraint node goes back to waiting for events , ( step 2 ). the above - described embodiment is , of course , merely illustrative of the principles of the invention . indeed , numerous other methods or apparatus may be devised by those skilled in the art without departing from the spirit and scope of the invention . for example , sisl may be advantageously implemented using an extensible markup language ( xml ). xml is a metalanguage for defining mark - up languages such as html . sisl can be implemented by defining an xlm document type declaration ( dtd ), corresponding to a grammar for reactive constraint graphs . sisl services are then specified in xml using dtd , and the sisl implementation of the service is automatically generated by the sisl infrastructure .	6
according to embodiments of the invention , ram in devices separate from the main memory (“ separate ram ”) may be used for a stack and temporary storage during bios execution . the separate ram is typically dedicated , in its normal usage , to one or more functional logic blocks of a chipset . for example , ram in a local area network ( lan ) controller is available during bios execution . a lan controller includes thousands of bytes of ram that are normally used to transmit data packets . however , applications are not able to send data packets until the main memory is fully configured , which does not occur until bios has finished performing this task . accordingly , there is ram in the lan controller which is unused until bios execution has completed , and is therefore available to speed bios execution itself . similarly , a universal serial bus ( usb ) controller includes ram unused for its normal function during bios execution , and therefore available to bios . various other ( non - main memory ) rams are available in a typical chipset . according to embodiments of the invention , a selected range of available physical address space supported by the central processing unit ( cpu ), but not populated by physical main memory , may be mapped to separate ram . usually , there is substantially more physical address space supported than is needed to address the actual physical memory ( e . g ., simm ( single inline memory module ) or dimm ( dual inline memory module ) dram ( dynamic ram )) installed in a system . in accordance with embodiments of the invention , during boot - up , an operational mode may be entered in which space in separate ram is made available to the bios program for a stack and temporary storage . in an embodiment , this operational mode may be set by programming an enable bit in the chipset . the enable bit may be automatically turned on or may be set by the bios routine . the bios routine may then initialize the stack pointer of the cpu to point to an address in the selected range of addresses mapped to the separate ram . according to this embodiment , subsequent instructions of the bios program may now include operations on a stack , such as “ push ” or “ pop ” instructions for calling subroutines , to write to or read from the stack pointed to by the cpu &# 39 ; s stack pointer . when the address in the stack pointer is asserted on the cpu &# 39 ; s address bus due to , for example , a push or pop instruction , and the chipset is in the operational mode for using separate ram for bios processing , the address is recognized as being within the range mapped to the separate ram , and the appropriate data is accordingly written to or read from the selected range of addresses in the separate ram . an exemplary embodiment of the invention is shown in fig1 . fig1 illustrates components in an intel ® chipset architecture used in personal computers . the chipset includes a cpu 100 connected to a memory controller ( mch or memory control hub ) 101 . the mch is connected to main memory 102 , and performs reads and writes to main memory 102 under the control of an instruction sequence executed by the cpu 100 . the mch is further connected to an i / o controller ( ich or i / o control hub ) 103 comprising a usb controller 104 . the usb controller 104 includes a separate ram 106 . as indicated above , according to embodiments of the invention , a selected range of available physical address space supported by the cpu , but not populated by physical main memory , may be mapped to space in separate ram 106 . in an embodiment , the addresses in the selected range may be higher than the highest location in main memory addressable by the mch , or “ top of memory .” top of memory is the highest address in the physical address space supported by the cpu at which there is corresponding physically populated memory . by mapping the selected range above top of memory , it is ensured that the address range assigned to ram 106 will not conflict with a range assigned to main memory 102 when main memory is enabled . accordingly , in this embodiment , when during the execution of a stack operation called for by the bios program 109 , the cpu attempts to access an address above top of memory , the mch recognizes that it is unable to perform the access and passes the address to the ich 103 . direct memory access ( dma ) engine 105 as shown in fig1 represents already existing logic in the ich for moving data between the ram 106 and main memory 102 under the normal operating circumstances ( i . e ., post - boot - up ) of the usb controller . normally , the cpu is unable to directly access the ram 106 . rather , the ram 106 is only used locally by the dma engine 105 and is treated as a first - in - first - out ( fifo ) buffer , though the ram is physically implemented as a ram with two ports . address decoder 107 and multiplexer ( mux ) 108 , on the other hand , represent elements of the present invention according to the exemplary embodiment under discussion . in this embodiment , the address decoder 107 may be configured to decode the selected range of addresses mapped to the ram 106 , enabling the cpu to access the ram 106 when an address within the selected range is passed to the ich by the mch . the mux 108 may be configured to be responsive to the operational mode set during system boot - up . for example , the mux may be controlled by the enable bit to select access to the ram 106 by either address decoder 107 or dma engine 105 . referring to fig2 , an illustrative example of an embodiment of an application of the invention follows . as shown in block 200 , a selected range of addresses including , for example , address x ′ ffff6000 , may be mapped to space in the ram 106 . address x ′ ffff6000 is typically well above top of memory . due to a system power - on or reset , main memory is unconfigured and the mch has no information about the main memory . the cpu executes its first instruction cycle , in which it attempts an access to memory . since the mch has no information about main memory , it transfers the attempted memory access to the ich . the ich searches for attached memory , and finds the eprom ( erasable programmable read - only memory ) 109 storing the bios program . accordingly , the cpu begins to fetch the instructions of the bios program , as shown in block 201 then , an operational mode for accessing the ram 106 to use space therein as a stack may be entered , as shown in block 202 . in an embodiment , the operational mode may be controlled by an enable bit . the enable bit may be automatically turned on at system power - up or reset , or may be set by an instruction in the bios program . the enable bit may control the mux 108 to select the input from the address decoder 107 rather than the dma engine 105 . once the bios has substantially completed its work , the enable bit will be reset to indicate that the ram 106 is to be returned to its normal usage , and no longer used for a stack . as shown in block 203 , as one of its initial steps , the bios program may set the stack pointer of the cpu to the value x ′ ffff6000 . while in current systems the bios program does initialize the cpu &# 39 ; s stack pointer , this occurs much later in the bios process . moreover , the stack pointed to is in main memory and can only be used after main memory is configured . by contrast , according to the present invention , a stack is available in separate ram substantially from the outset of the bios process . once the cpu &# 39 ; s stack pointer is initialized , the bios program may execute stack operations which will access the ram 106 , including calling subroutines , as shown in block 204 . whenever the cpu 100 asserts an address within the range mapped to ram 106 and the enable bit is set , the mch 101 will pass the address to the ich 103 , since the address is not one that the mch can handle . the address will appear on an internal address bus of the ich and be decoded by address decoder 107 to access the stack in ram 106 . as discussed above , the bios code is typically very lengthy and would be greatly expedited if enabled to use a stack . availability of a stack enables the bios program to be coded more easily and compactly , since subroutines may be called . further , parallelism is possible due to multi - threading , and consequently the bios process is significantly speeded up . once the bios program has executed past a certain point , for example , once main memory is fully configured , the stack in separate ram is no longer needed and normal chipset operations are possible . accordingly , the cpu &# 39 ; s stack pointer may be re - programmed to point to main memory and the enable bit may be reset so that accesses to ram 106 are made only by dma engine 105 , as shown in block 205 . in an alternative embodiment of the invention , a separate ram may be shared for use in its normal or dedicated function , and also for providing stack space to the bios program . for example , bios processing may advance to a stage wherein normal operations by the usb controller are possible , but main memory is still not fully configured , and therefore a stack in separate ram is still needed or useful . to enable usb operations to proceed at the same time as bios processing continues , a portion of the ram 106 could be reserved for access by the dma 105 , while another portion could be set aside for a stack for the bios program . fig1 b illustrates such an alternative embodiment . in fig1 b , ram 106 is divided into a first portion 115 and a second portion 116 . the first and second portions need not be equal in size and can take on any desired relative proportions . the first portion 115 may be set aside for a stack and accessible as described in the foregoing . that is , an operational mode may control mux 108 to determine whether the first portion 116 is accessed by address decoder 107 or by dma engine 105 . second portion 116 , on the other hand , may be coupled to dma engine 105 and accessible independently of the operational mode controlling the mux . thus , second portion 116 may be available for operations by the usb as soon as bios processing has advanced to a stage wherein such operations are possible . while the efficiency of the usb operations might be somewhat reduced during a period of sharing the ram 106 , sharing would allow usb operations to proceed in parallel with bios processing , thereby reducing delay in available chipset functions . once bios processing was complete , the stack space could be returned to the usb controller , which would then operate with full efficiency . a bios program including computer - executable instructions according to embodiments of the present invention may be stored and transported on a computer - usable medium such as diskette , magnetic tape , disk or cd - rom . the instructions may be downloaded to a second storage medium such as eprom 109 , from which they may be fetched and executed by a processor such as cpu 100 to effect the advantageous features of the invention . several embodiments of the present invention are specifically illustrated and described herein . however , it will be appreciated that modifications and variations of the present invention are covered by the above teachings and within the purview of the appended claims without departing from the spirit and intended scope of the invention .	6
hyperlipidemia relates to plasma cholesterol and triglyceride levels that exceed “ normal ”— arbitrarily defined as the 95 th percentile . but it is now clear that “ ideal ” or “ optimal ” levels are far below the normal levels of the population . a large proportion of united states adults have concentrations above the optimal range and should be considered to have hyperlipoproteinemia . j . hardman , supra , at 875 . in a preferred embodiment of the invention , a composition is administered that simultaneously affects several different mechanisms in the production of atherosclerosis , including the levels of ldl and hdl cholesterol , through inhibiting hmg - coa reductase , correcting any consequent depletion of coenzyme q 10 , and inhibiting the oxidation of ldl into lipid peroxidases . in another embodiment , chromium or inositol hexanicotinate , or both , is added for control of insulin and lipid metabolism and additional control or reduction of cholesterol levels . one theory is that both the presence of elevated plasma ldl and its oxidative modification within the artery wall is required to produce atherosclerosis . steinberg , supra . indeed , then the use of an appropriate antioxidant in vivo should decrease the rate at which ldl is taken up by macrophage foam cells and slow the development of the fatty streak lesion . this phenomena has been demonstrated in receptor deficient rabbits treated with probucol as an antioxidant . parthasarathy , supra . red yeast is a mixture of several species of monascus fungi ; the predominant one is monascus purpureus . monascus was first described in 1884 . van tieghem , 31 bull . soc &# 39 ; y botany france 226 ( 1884 ). monascus is has been used for centuries as in wine fermentation and as a food colorant and preservative . see http :// www . allok . com / ehistorie . htm . a traditional chinese product used to make rice wine and as a preservative is based on rice that has been fermented with monascus purpureus . heber , 69 am . j clinical nutrition 231 - 236 ( 1999 ), citing stuart , chinese materia medica — vegetable kingdom ( 1979 ). this product also has a tradition of being useful in “ improving the blood circulation .” d . bensky & amp ; r . barolet , chinese herbal medicine : materia medica ( revised ed . 1993 ). the medical applications of red yeast were described in the ancient chinese pharmacopoeia , pen ts &# 39 ; ao kang mu , published during the ming dynasty ( 1368 - 1644 ). it describes red yeast as useful for treating indigestion , diarrhea , and improving the health of the spleen , stomach , and circulation . in ancient china , monascus was called “ hongqu ” and was said to have the ability to cure stomach and spleen , to strengthen the blood , and the principle to preserve and endorse the common qi interdependent . ben cao gang mu von li shi - zen , book of medicinal herbs ( 1590 ). more recently , researchers discovered that a strain of monascus yeast used in the production of red yeast rice naturally produced a substance that inhibits cholesterol synthesis called monacolin k ( lovastatin ), along with a group of 8 monacolin - related substances that are hmg - coa reductase inhibitors . endo , supra . experiments in rabbits revealed that one extract , xuezhikang , lowered cholesterol levels by 44 % and 59 % at doses of 0 . 4 and 0 . 8 mg / kg , respectively . id ., see also li , 18 ( 1 ) nutrition research 71 - 81 ( 1998 ). these doses correspond to human doses of 24 mg and 48 mg ( for a 60 - kg person ). chinese red yeast rice costs only $ 20 - 30 per month at such doses , compared to the average cost of $ 187 / month for a cholesterol - lowering drug . id . the effects of monascus purpureus rice in 324 patients were compared with the effects of another chinese herbal medicine , jiaogulan ( gynostemma pentaphylla ) on serum cholesterol . wang , 58 ( 12 ) current therapeutic research 964 - 978 ( 1997 ). eligible patients were recruited if their serum total cholesterol ( tc ) was 240 mg / dl ( 5 . 95 mmol / l ) or higher , ldl - cholesterol was 130 mg / dl ( 3 . 41 mmol / l ), or triglycerides ( tg ) were 200 - 400 mg / dl ( 2 . 26 - 4 . 52 mmol / l ). in addition , hdl - cholesterol was 40 mg / dl ( 1 . 04 mmol / l ) or less for men or 45 mg / dl ( 1 . 16 mmol / l ) for women . after 8 weeks , total cholesterol decreased by 34 . 5 % ( p & lt ; 0 . 001 ) in treated patients while the positive controls had only an 8 . 3 % decrease . those patients with pretreatment cholesterol over 300 mg / dl had a greater reduction than did those whose cholesterol prior to treatment was below 240 mg / dl . and while the increase in hdl cholesterol was minor for those with pre - treatment levels & gt ; 45 mg / dl , significant increases were observed in those with pretreatment hdl of 35 - 45 mg / dl ( 16 %) and less than 35 mg / dl ( 25 . 1 %). coenzyme q 10 ( ubiquinone ) is a naturally occurring substance that plays a central role in oxidative respiration as a catalyst and has a separate direct membrane stabilizing effect . in man , vitamin e , beta - carotene , and coenzyme q 10 all appear to be endogenous antioxidants in ldl . epidemiologic data suggest a negative correlation between coronary disease and levels of vitamin e . witztum & amp ; steinberg , supra . it is also an antioxidant and free radical scavenger , and protects ischemic tissue from the damage that occurs when blood flow is restored ( reperfusion damage ). in studies of cardiac patients , deficiencies of the enzyme were found in 75 % of 132 biopsy specimens of heart tissues , and 20 % of 406 blood samples . studies performed by several different groups of researchers have shown that supplementation with coenzyme q 10 improves the signs and symptoms of cad at doses of 1 . 5 mg / kg per day ( 90 mg in a 60 kg person ), 150 mg / day and 600 mg / day . greenberg & amp ; frishman , 30 j . clinical pharmacology 596 - 608 ( 1990 ) at p . 599 . earlier clinical studies in japan used a dose of 5 mg , and later a dose range of 25 - 100 mg . folkers , et al , 2 j . molecular medicine 431 - 460 ( 1977 ). coenzyme q 10 and alpha - tocopherol in the ldl cholesterol are depleted faster on lovastatin therapy during peroxidative insult . the finding was associated with a shortened lag time of conjugated diene formation suggesting diminished resistance of ldl particles to the early phase of oxidative stress . a crossover study was conducted to investigate the effects of supplementation with 180 mg per day ubiquinone ( coenzyme q 10 ). there were no differences in the measurements for cholesterol , ldl , hdl , the ldl / hdl ratio , triglycerides , or apolipoprotein levels between treatment arms . but in the oxidative studies , the total depletion time of ldl coenzyme q 10 was 49 . 6 % longer on lovastatin but was comparable to pre - treatment levels with supplementation . the authors concluded that the improvement was scarce and its clinical relevance remained open . palomaki , 39 j . lipid research 1430 - 1437 ( 1998 ). in men with familial combined hyperlipidemia , ldl was more prone to oxidation and the coenzyme q 10 in the ldl was more predominantly in a reduced state , suggesting the coenzyme q 10 plays an important role in protecting ldl from in vivo oxidation . de rijke , 17 ( 11 ) arteriosclerosis , thrombosis , and vascular biology 127 - 133 ( 1997 ). this was studied by comparing patients treated with 20 - mg simvastatin per day with or without supplementation with coenzyme q 10 at 100 mg per day . in both groups , both total cholesterol and ldl cholesterol declined and results were highly statistically significant . but levels of coenzyme q 10 , which started out similar , decreased in the group treated with simvastatin alone , yet increased in the group that was supplemented . bargossi , 15 molecular aspects of medicine s187 - s193 ( supp . 1994 ). minimally oxidized ldl is believed to be involved in the early stages of atherosclerosis . in several studies of the hgm - coa reductase induced coenzyme q 10 deficiency , supplementation with coenzyme q 10 at 100 mg to 180 mg was shown to correct the depletion of the enzyme within the ldl particle . id . supplementation with coenzyme q 10 , 100 mg per day for 30 days resulted in increased coenzyme q 10 levels in all three ldl subfractions ( p & lt ; 0 . 01 ) in each of the 10 subjects studied . small increases in vitamin e were observed , as well as a significant decrease in hydroperoxide levels in the ldl 3 subfraction , which is commonly elevated in patients at high risk for coronary artery disease . alleva , 92 proc . nat &# 39 ; l acad . sci . 9388 - 9391 ( 1995 ). in an open label , eight - year study , 424 patients with various forms of cardiovascular disease added coenzyme q 10 , 75 mg to 600 mg / day , to their diets . improvements in myocardial function ( 58 %) and decreased dependency on drugs ( 43 %) were noted . langsjoen , 15 molecular aspects of medicine s165 - s175 ( supp . 1994 ). several prospective studies suggest an inverse association between dietary intake or plasma concentrations of antioxidants and cvd . in a cross - cultural study of 16 european populations , the strongest inverse correlation in this study was observed between ischemic heart disease and plasma concentration of vitamin e , a well - established anti - oxidant . meydani , 345 ( 8943 ) lancet 170 - 175 ( 1995 ). however , two earlier studies in finland and the netherlands reviewed by meydani in 1995 did not find an association between serum vitamin e and subsequent cvd mortality . in men , a borderline significant association was found for dietary intake of vitamin e alone , but it was much stronger for vitamin e supplement users consuming above 100 iu vitamin e daily for at least 2 years . id . in their review of published studies , jha et . al , reported , inter alia , the results of the u . s . nurses &# 39 ; health study . this study followed 87 , 000 female nurses for an average of 8 years . about 13 % of women regularly used vitamin e supplements . these women , after adjustment for age , smoking , alcohol use , menopausal status , hormone use , exercise , aspirin use , hypertension , cholesterol intake , diabetes , caloric intake , and vitamin c and beta - carotene intake , had a statistically significant reduction in relative risk of 31 % ( 95 % confidence limit , 3 %, to 51 %) for non - fatal myocardial infarction and death from cardiovascular disease in comparison with women who did not use the supplements . the absolute risk reduction was 3 . 4 women per 10 , 000 woman - years ( a woman - year is one woman followed for one year ) of follow - up ( 8 . 5 compared with 5 . 2 per 10 , 000 woman - years of follow - up ). jha , et al ., 123 ( 11 ) annals of internal medicine 860 - 872 ( 1995 ). vitamin e is a mixture of tocopherols . d - alpha - tocopherol has the highest biological activity and is the most widely available form of vitamin e in food . the other isomers ( beta , gamma , and delta ) are less biologically active than d - alpha - tocopherol . the commercially available synthetic forms of vitamin e comprise an approximately equal mixture of eight stereoisomeric forms of alpha - tocopherol . for practical purposes , 1 international unit ( iu ) of vitamin e is referred to as 1 mg of the synthetic form , racemic alpha - tocopheryl acetate , and the natural form of d - alpha - tocopherol has a biopotency of vitamin e equal to 1 . 49 iu . vegetables and seed oils including soybean , safflower and corn , sunflower seeds , nuts , whole grains , and wheat germ are the main sources of the tocopherols . meydani , supra . researches have observed a relation between deficient selenium ( an antioxidant ) and an excess risk of acute myocardial infarction as well as death from chd and cvd in eastern finland . low serum selenium levels and lipid peroxidation in vivo are associated with accelerated progression of carotid atherosclerosis in eastern finnish men . in a 1994 study , salonen reported that a subject &# 39 ; s hair mercury content correlated most strongly of all cardiovascular risk factors . mercury forms an insoluble complex with selenium ( mercury selenide ), thus binding selenium in an inactive form that cannot serve as a cofactor for glutathione peroxidase , an important scavenger of peroxides and lipid peroxides . salonen , 91 ( 3 ) circulation 645 - 655 ( 1995 ). but another study based on 251 subjects who had infarctions and an equal number of healthy controls matched by age , smoking status , and time from randomization , showed no statistical association between plasma selenium and myocardial infarction . salvini , 76 ( 17 ) am . j . cardiology 1218 - 1221 ( 1995 ). deficiency of chromium , a trace element , has been associated with lipid abnormalities and an increased risk of atherosclerotic disease . newman measured serum chromium levels in 32 subjects referred for selective coronary arteriography . patients with catheterization - proven coronary disease had significantly lower serum chromium levels and higher serum triglyceride ( tg ) than patients without coronary disease . newman ha , et . al . 24 ( 4 ) clinical chemistry 541 - 4 ( 1978 ). chromium is a cofactor in the maintenance of normal lipid and carbohydrate metabolism and its supplementation in normal volunteers has been shown to reduce the levels of total cholesterol , ldl , and apolipoprotein b , and raise levels of hdl . press , geller & amp ; evans , 152 ( 1 ) western j . medicine 41 - 5 ( 1990 ). chromium and two molecules of nicotinic acid form a biologically active complex referred to as “ glucose tolerance factor ,” which has been reported to enhance the action of insulin . jeejeebhoy confirmed the its importance in humans when he successfully treated an insulin - resistant diabetic patient with only chromium supplementation after she had become chromium deficient after 3 years of parenteral nutrition . see lee & amp ; reasner , 17 ( 12 ) diabetes care 1449 - 1452 ( 1994 ). an increase in hdl cholesterol levels was observed after chromium treatment in 23 healthy volunteers and in 72 hypertensive men on beta - blockers . id . other groups have shown chromium to improve the lipid profile , hyperglycemia , and body weight in persons with obesity or diabetes . type 2 diabetics were treated with 100 - mcg chromium bid or 500 mcg bid or placebo . the higher dose group showed lower blood sugar and cholesterol than the placebo group after 2 and 4 months . anderson , 46 ( 11 ) diabetes 1786 - 91 ( 1997 ). chromium supplementation is also useful for elevated triglycerides . in a prospective , double - blind , cross - over study of 14 men and 16 women supplementation with chromium picolinate for 2 months resulted in a statistically significant reduction in triglyceride levels of 17 . 4 % ( 133 vs . 161 mg / dl ; p & lt ; 0 . 05 ). lee & amp ; reasner , supra . inositol hexaphosphate is a form of nicotinic acid that does not produce a flush . nicotinic acid ( niacin , a water - soluble b vitamin ) has been shown to decrease triglyceride , increase hdl cholesterol , lower ldl cholesterol , and decrease lipoprotein ( a ); it also decreases fibrinogen . gotto jr ., 82 ( 9a ) am . j . cardiology 22q - 25q ( 1998 ). it was also shown to increase levels of hdl - cholesterol by 35 %, to 1 . 20 +/− 0 . 21 mmol / liter ( 46 . 5 +/− 8 . 1 mg / dl ) at a mean dose of 2 , 250 mg / day . zema , 35 ( 3 ) journal of the american college of cardiology 640 - 6 ( 2000 ). nicotinic acid was first reported to be hypolipidemic in 1955 . large doses ( 3 to 6 g / day ) rapidly decrease vldl and ldl and dramatically increase hdl even as much as 20 or 30 mg / dl . but it causes numerous side effects , most importantly an intense flushing and pruritis . abnormalities of hepatic function , including jaundice , are potentially serious and can occur with 2 - g day or delayed - release products . elevated fasting glucose and delayed glucose tolerance occur frequently and rare side effects include reversible optic maculopathy , toxic amblyopia , arrhythmias , and orthostatic hypotension . see j . hardman at pp . 889 - 90 . probucol , a potent antioxidant , was marketed for several years as a hypolipidemic but is now considered only a second or third line agent because of its erratic ldl response and persistent ability to lower hdl levels . it inhibits atherosclerosis in hypercholesterolemic rabbits and non - human primates independently of its hypolipidemic effects , supporting the hypothesis that oxidation is a key step in its development . j . hardman , supra , at pp . 891 - 2 . short - term adverse effects include gastrointestinal symptoms , headache , dizziness and increase in the qt interval i many patients . all of the ingredients used in the compositions of the present invention are obtainable commercially by suppliers well known to those skilled in the art of nutritional supplement formulation . red yeast rice , although also commercially available , may alternatively be prepared by traditional means . indeed , the solid state fermentation of rice by monascus has a long tradition in east asian countries ; its fermentation dates back at least to the first century ad . heber , supra . the fermentate is obtained as scarlet to purple red grains , which have the original rice grain structure well preserved . the commercial product is mostly a ground powder , which is know as “ ang kak ” or “ hong qu ” in chinese the japanese name for the product is “ koji ”. traditional or improved red yeast can be prepared by traditional fermentation procedures or their modification . in ancient china , monascus was called “ hongqu ” and was first described in the 16 th century . b . c . g . m . von li shizhen , book of medicinal herbs ( 1590 ). it was said to have the ability to cure stomach and spleen , to strengthen the blood , and the principle to preserve and endorse the common qi interdependent . id . the preparation of hongqu was described as follows : you take 1 dan and 5 dou jing mi [ the rice ]. clean this with water in a bowl and let it soak for one night . then you &# 39 ; ll cook it like normal food . further you separate [ the rice ] in 15 portions and add jin pilzmutter . roll and knead [ the mass ] to distribute all equally . form [ all ] together to one portion and cover it carefully with a silkcloth . first heat [ the whole ], then take off the silk and splay [ the rice pulp ]. if the rice pulp is warm , push it together to a heap . again cover it carefully [ with a silkcloth ]. next day at noon again make three heaps [ of the pulp ], let it rest for a while and form of each part five heaps . let it rest a short time . then form all together to a heap . then let it rest for w while . then form 15 pieces . heat a little and then form again a heap . repeat this 5 times . at the third day fill a big tun with fresh water . dip short time and process wet and form again a heap . handle again with this method . at the fourth day again dip it in fresh water if the fungus falls for half and swim for half at the surface , then again use the method from above : dip shortly . if the fungus completely is at the surface , it &# 39 ; s ready . take it out and dry it in the sun . if this rice responds , we call it shenghuang , a fresh yellow color . if you add hongqu to alcohol , fish sauces or hacked meat , it results a fresh and appealing red . if it doesn &# 39 ; t appeal to the heart his quality isn &# 39 ; t very well . if added to medicaments , take stored , old hongqu , that &# 39 ; s good . according to another early reported method ( sung , t &# 39 ; ien kung k &# 39 ; ai wu 291 - 294 ( 1637 , sun trans . 1966 )), red yeast can be prepared by the fermentation of washed and cooked non - glutinous rice using red wine mash , natural juice of polygons grass , and alum water . the rice is fermented in open air for 7 days on bamboo trays under very clean conditions . the rice changes its color from white to black , black to brown , and brown to red and then red to yellow , which is then harvested as red yeast . according to an alternative traditional method , non - glutinous rice can be fermented in a hole in the ground lined by bamboo mats , which is securely covered . fermentation is allowed to take place underground for one year or more , up to four years . wo 98 / 14177 ( 1998 ), at p . 9 . the traditional method has been improved with modern fermentation techniques and equipment to more precisely control temperature , ph , pressure and other fermentation parameters thus reducing the time required . one example is as follows : culture media containing kidney - bean juice 2 %, sugar 4 %, yeast 0 . 5 % are added to rice ( 40 - 80 ml per 100 g ) and sterilized by heat while the ph is maintained at ph3 to 8 . red yeast fungi monascus purpureus went strain m4184 is added and cultured at 15 - 35 ° c . for 9 days . at the end of the fermentation process , the fermentation broth is drained and discarded , while the solid residue is sterilized by heat , dried and crushed into powder . id . this powder can be used directly in the various compositions and formulations provided in the present invention . monascus purpureus is available commercially around the world , through distributors such as dr . win fried bear at friedrich - breuer - str . 86 - d - 53225 bonn , allok at lachenmeyrs tr . 18a , 81827 , munchen , germany and samlong chemical co ., ltd ., p . b . box 65 , changzhou , jiangsu , china . coenzyme q 10 , mixed tocopherols ( vitamin e ), selenium , chromium , and inositol hexaphosphate are available commercially , in bulk and wholesale , from suppliers well known to those with ordinary skill in the art . for instance , vitamin e may be obtained from ava health po box 730 , grove city , ohio 43123 - 0730 and wholesale vitamins usa , inc ., of brooklyn , n . y . offers over 8 , 000 vitamins at wholesale prices . any dosage form may be employed for providing the patient with an effective dosage of the composition . dosage forms include tablets , capsules , dispersions , suspensions , solutions , capsules , transdermal delivery systems , etc . . . tablets and capsules represent the most advantageous oral dosage unit form . any method known to those of ordinary skill in the art may be used to prepare capsules , tablets , or other dosage formulations . pharmaceutically acceptable carriers include binding agents such as pregelatinized maize starch , polyvinylpyrrolidone or hydroxypropyl methycellulose ; binders or fillers such as lactose , pentosan , microcrystalline cellulose or calcium hydrogen phosphate ; lubricants such as magnesium stearate , talc or silica ; disintegrants such as potato starch or sodium starch ; or wetting agents such as sodium lauryl sulfate . tablets or capsules can be coated by methods well known to those of ordinary skill in the art . according to one aspect of the invention a composition is provided comprising a pharmaceutically acceptable combination of the composition and at least one carrier . pharmaceutically acceptable carriers for inclusion into the present compositions include carriers most suitable for combination with lipid - based drugs such as diluents , excipients and the like which enhance its oral administration . suitable carriers include , but are not limited to , sugars , starches , cellulose and derivatives thereof , wetting agents , lubricants such as sodium lauryl sulfate , stabilizers , tabletting agents , anti - oxidants , preservatives , coloring agents and flavoring agents . reference may be made to remington &# 39 ; s pharmaceutical sciences , ( 17th ed . 1985 ) for other carriers that would be suitable for combination with the present compositions . as will be appreciated , the pharmaceutical carriers used to prepare compositions in accordance with the present invention will depend on the administrable form to be used . according to one embodiment of the invention , the novel composition of the present invention comprises red yeast fermented on rice , coenzyme q 10 , chromium , selenium and mixed tocopherols and inositol hexanicotinate , and is formulated for oral administration . oral dosage forms formulated in accordance with standard pharmaceutical practice may be employed . capsules are a particularly useful vehicle for administering the present composition . the administration of the composition is preferably in accordance with a predetermined regimen , which may be at least once daily and over an extended period of time as a chronic treatment , and could last for one year or more , including the life of the host . the dosage administered will depend upon administration frequency , the blood level desired , other concurrent therapeutic treatments , the condition &# 39 ; s severity , whether the treatment is for prophylaxis or therapy , the patient &# 39 ; s age , the severity of cholesterol elevation , and the like . in a preferred aspect of the invention , a composition of the present invention is administered to reduce or control blood cholesterol levels in persons having a total cholesterol of 240 mg / dl ( 5 . 95 mmol / l ) or higher . in another embodiment of the invention , the compositions are administered to reduce levels of ldl - cholesterol in persons with an ldl - cholesterol of 130 mg / dl ( 3 . 41 mmol / l ) or higher . in yet another embodiment of the invention , the compositions are administered to reduce triglycerides in persons having blood triglycerides of 200 mg / dl ( 2 . 26 mmol / l ) or higher . in another embodiment , a composition of the present invention is administered to raise levels of hdl to persons with an hdl - cholesterol of 35 mg / dl ( 1 . 04 mmol / l ) or lower to reduce the risk of atherosclerosis associated with low hdl levels . the compositions and methods of the present invention may also be utilized to improve or maintain vascular health in specific organ systems including the cardiovascular system , the cereberovascular system , the peripheral vascular system and the intestinal vascular system . according to an additional embodiment , the compositions of the present invention may be admixed by conventional methods and may be administered by an alternative route such as suppository , spray , liquid , powder , liposome , dermal patch , and inhalant . these methods are well known to those skilled in the art . for example , liposomes may be formulated according to methods such as those of u . s . pat . no . 5 , 853 , 755 , to foldvari , u . s . pat . no . 4 , 235 , 871 to papahadjopoulos , et al , or u . s . pat . no . 4 , 708 , 861 to popescu et al ( liposome - gel combination ). sublingual and transdermal methods are also well known to those skilled in the art , e . g ., u . s . pat . no . 5 , 922 , 342 to shah , et al describes a sublingual formulation and u . s . pat . no . 4 , 997 , 655 to nagy , et al describes a transdermal administration method . in a specific embodiment of the invention , the composition comprises between 50 mg and 3 . 6 gm red yeast rice , between 5 and 300 mg coenzyme q10 , between 10 mcg and 1 mg chromium , between 5 and 1 g inositol , between 10 mcg and 1 mg selenium , and between 5 iu and 800 iu mixed tocopherols . in yet another embodiment of the invention , the composition comprises between 100 mg and 2 . 4 gm red yeast rice , between 5 and 250 mg coenzyme q10 , between 10 mcg and 500 mcg chromium , between 10 and 800 mg inositol , between 10 mcg and 500 mcg selenium , and between 5 iu and 400 iu mixed tocopherols . in yet another embodiment of the invention , the composition comprises between 100 mg and 1 . 2 gm red yeast rice , between 5 and 150 mg coenzyme q 10 , between 10 mcg and 300 mcg chromium , between 20 and 500 mg inositol , between 10 mcg selenium , and between 5 iu and 200 iu mixed tocopherols . and in yet another embodiment of the invention , the composition may be administered in a daily dose of between 50 mg and 1 . 6 gm red yeast rice , between 10 and 600 mg coenzyme q10 and between 5 iu and 800 iu mixed tocopherols . in a preferred embodiment , the composition is administered in four tablets each comprising about 500 mg red yeast rice , about 15 mg coenzyme q 10 about 50 mcg chromium , about 13 mg inositol , about 50 mcg selenium , and about 20 iu mixed tocopherols to provide a total daily dose of about 2 gm red yeast rice , about 60 mg coenzyme q 10 , about 200 mcg chromium , about 52 mg inositol , about 200 mcg selenium and about 80 iu mixed tocopherols . the administration of the composition would be in accordance with a predetermined regimen , which would be at least once daily and over an extended period of time as a chronic treatment , and could last for one year or more , including the life of the host . the dosage administered will depend upon the frequency of the administration , the blood level desired , other concurrent therapeutic treatments , the severity of the condition , whether the treatment is for prophylaxis or therapy , the age of the patient , the levels of ldl - cholesterol and hdl - cholesterol in the patient , and the like . the invention will be further illustrated by the following non - limiting examples : a study of the effect of the red yeast rice , 200 mg qid , coenzyme q 10 10 mg qid , mixed tocopherols 10 iu qid , selenium 20 mcg qid , chromium 20 mcg qid , and inositol 20 mg qid on hdl - cholesterol , non hdl - cholesterol , and total cholesterol concentrations in the blood of men with elevated cholesterol levels is conducted over a 6 month period . a statistical analysis is performed to compare the resulting cholesterol levels of the test and a control ( placebo ) group to determine if a significant improvement in cholesterol levels results from administration of the test preparation . sixty men having total plasma cholesterol of between 240 and 300 mg / dl are selected for inclusion in the statistical study . two weeks prior to the start of the study each subject completes a two day dietary intake record and is interviewed by a registered dietitian to calculate each individual &# 39 ; s daily energy requirement for a basal low fat , low cholesterol national cholesterol education program step i diet . each subject is given a booklet published by the american heart association containing a long list of foods , along with a calculated “ fat gram prescription ” which complies with the criteria for the basal diet . all subjects follow the basal diet for a period of at least fourteen days . after this , baseline blood samples are drawn on two separate days , and the subjects are randomly assigned to one of two treatment groups , the test capsules or matching placebo capsules . both groups continue on their basal diet and incorporate four tablets of the test composition in the diet . the effects of the dietary supplementation on total cholesterol , hdl - cholesterol , and non - hdl cholesterol , as well as dietary intake , body mass index , and physical activity are evaluated using multiple linear regression analysis and a standard students t - test . in each analysis the baseline value of the outcome variable is included in the model as a covariant . treatment by covariant interaction effects is tested by the method outlined by weigel & amp ; narvaez , 12 controlled clinical trials 378 - 94 ( 1991 ). if there are no significant interaction effects , the interaction terms are removed from the model . the regression model assumptions of normality and homogeneity of variance of residuals are evaluated by inspection of the plots of residuals versus predicted values . detection of the temporal outset of effects is done sequentially by testing for the presence of significant treatment effects at 18 , 12 , and 6 weeks , proceeding to the earlier time in sequence only when significant effects have been identified at each later time period . in addition , differences between groups in nutrient intake , physical activity , and body mass index ( ht / wt . sup . 2 ) at each time point are compared using one - way analysis of variance . changes from the baseline within each group are evaluated using paired t - tests . in addition , analysis of variance is performed on all baseline measurements and measurable subject characteristics to assess homogeneity between groups . all statistical procedures are conducted using the statistical analysis system ( sas institute inc ., cary , n . c .). an alpha level of 0 . 05 is used in all statistical tests . a statistically significant increase in hdl - cholesterol and the decrease in non - hdl cholesterol including ldl - cholesterol are observed in the blood of the treated subjects upon completion of the study but not the controls . the differences between the levels of hdl - cholesterol and non - hdl cholesterol including ldl - cholesterol in the treated subjects and controls are statistically significant . a composition of the following formulation was prepared in table form by standard methods : 4 tablets per day is the recommended dosage for an average weight adult human ( 70 - kg ). the invention has been described in detail with particular reference to preferred embodiment thereof . however , it will be appreciated that those skilled in the art , upon consideration of this disclosure may make variations and modifications within the spirit and scope of the invention .	8
fig1 represents the basic electrical circuit and drive parts of a magnetic tape drive arrangement without pressure rollers in accordance with the invention . the arrangement comprises a magnetic tape transport device with a take - up reel 2 driven by a take - up motor 6 and a feed reel 1 driven by a feed motor 7 ; of cpurse , the feed motor 7 is not always necessary and may be replaced by a braking device . this magnetic tape transport feeds the magnetic tape 3 along a capstan 4 , which is driven by a capstan drive motor 5 . for the stake of simplicity the recording and playback transducers co - operating with the magnetic tape 3 are not shown . these transducers may be stationary magnetic heads or rotary heads as frequently used in video tape recorders . the capstan drive motor 5 is energized by an energizing circuit 8 in order to drive the magnetic tape 3 with the desired speed . for this purpose the motor 5 may be coupled to a tachogenerator , whose output signal is compared with a reference signal . the arrangement further comprises a motor current detector 9 , which detects the current consumed by the capstan drive motor 5 , an acceleration detector 10 , which supplies a signal which is a measure of the acceleration of the capstan 4 , and a reference source 12 . the output signals of the detectors 9 and 10 and of the reference source 12 are supplied to a control signal generator 11 , which supplies a control signal for controlling the speed of the take - up motor 6 and , as the case may be , for a feed motor 7 . it is also possible to effect control by means of one feed motor only . if the capstan 4 exerts a driving torque t d on the magnetic tape 3 , then t d = t - t o - t v , where t is the total torque produced by the motor 5 , t o the zero - load torque representing the losses , and t v the accelerating torque . if the motor 5 is a d . c . motor , then ( t - t o )= k 1 ( i - i o ), where i is current consumed by the motor 5 and detected by the detector 9 , i o is the zero - load current in the motor 5 , which current is represented by the reference source 12 , and k 1 is a constant . the accelerating torque t v satisfies the equation t v = j ( d 2 φ )/( d t 2 ), where j is the moment of inertia of the rotor and capstan 4 and φ the capstan phase ; thus , t v = k 2 . a , where k 2 is a constant and a is the angular acceleration of the capstan 4 . the control signal generator 11 generates a signal proportional to k 1 ( i - i o )- k 2 a . by means of this signal the take - up motor is so controlled as to minimize this signal , so that the torque t d exerted on the tape 3 by the capstan 4 is minimal and the tape 3 can thus be driven by the capstan 4 without the use of a pressure roller and without the occurrence of slip . fig2 shows the relevant parts 9 , 10 and 11 of a first embodiment of an arrangement in accordance with the invention in more detail . in this embodiment a tachogenerator 13 -- which may also serve as speed reference for the energizing circuit 8 -- is employed , which is coupled to the capstan motor 5 . the acceleration detector 10 comprises this tachogenerator 13 and a differentiator 14 , which derives a signal proportional to the angular acceleration of the capstan from the tachosignal . the constant factor k 2 may be realized either in this differentiator , or in a further circuit ( for example a differential amplifier 17 ). the motor current detector 9 comprises a resistor 15 , which is included in the motor supply line and which generates a voltage ir , in which r is the value of the resistor 15 . the reference source 12 generates a voltage i o r . the signal generator 11 comprises a differential amplifier 16 , to which the voltages ir and i o r are applied , which differential amplifier may have a gain k 1 / r and then supplies a voltage equal to k 1 ( i - i o ) as output signal . if desired , the factor k . sub . 1 may be generated in a further amplifier . the output signal of amplifier 16 and the output signal of differentiator 14 are applied to a differential amplifier 17 , a voltage which is proportional to the desired signal k 1 ( i - i o )-- k 2 a appearing on the output 18 of said differential amplifier . fig3 shows the relevant parts 9 , 10 and 11 of a second embodiment of an arrangement in accordance with the invention in more detail . in this embodiment the back -- e . m . f . e of the d . c . motor 5 is employed for detecting the angular acceleration a of the capstan , which acceleration is proportional to the time derivative of e with a constant factor k 3 : a = k ( de / 3dt . a complication in this respect is the internal resistance r a of the motor 5 . except for the acceleration detector 10 this embodiment is further identical to that of fig2 . the acceleration detector 10 comprises an amplifier 19 , which measures the voltage across the motor 5 in series with the measuring resistor 15 and amplifies or attenuates this voltage by a factor r / r a . the output voltage of this amplifier 19 and the voltage across resistor 9 are applied to a differential amplifier 20 , so that the output signal of this amplifier is proportional to the e . m . f . e of the motor 5 . this voltage is differentiated with a differentiator 14 . if the amplifier 20 and / or differentiator 14 provide an amplification by a factor ( r a . k 2 )/( r . k 3 ), the output signal of amplifier 17 will be proportional to the desired signal k 1 ( i - i o )-- k 2 a . apart from the embodiments described in detail , numerous modifications are possible in order to realize the desired function k 1 ( i - i o )-- k 2 a with differentiators and amplifiers etc . it is for example possible to differentiate the total voltage across the motor 5 and the resistor 15 with a differentiator and to differentiate the difference between the voltage across the resistor 15 and the reference voltage from the source 12 with another differentiator , and to take the difference of the two differentials , allowance being made for the correct factors . in order to control the speed of the take - up motor 6 , the signal from output 18 may be applied to an energizing circuit for the motor 6 and , as the case may be , applied in phase opposition to an energizing circuit for the feed motor 7 . these signals , as the case may be with the inclusion of an additional control amplifier , should then be applied so that in the case of a positive signal on output 18 -- which corresponds to a positive torque td exerted on the magnetic tape 3 by the capstan 4 the take - up motor will produce a greater torque and in the case of a negative signal on output 18 the take - up motor 6 will produce a smaller torque . for a correct choice of the constants k 1 and k 2 the magnetic tape can then be driven by the capstan without pressure roller and without the occurrence of slip . in addition , the motor 6 , and as the case may be the motor 7 , may be connected to a separate control , known per se , for controlling the torque of said take - up motor 6 and any feed motor 7 , in conformity with the amounts of tape on the reels 1 and 2 .	6
the term “ tissue ” is used in the general sense herein to mean any transplantable or implantable tissue , the survivability of which is improved by the methods described herein upon implantation . in particular , the overall durability and longevity of the implant are improved , and host - immune system mediated responses , are substantially eliminated . the terms “ transplant ” and “ implant ” are used interchangeably to refer to tissue , material or cells ( xenogeneic or allogeneic ) which may be introduced into the body of a patient . the terms “ autologous ” and “ autograft ” refer to tissue or cells which originate with or are derived from the recipient , whereas the terms “ allogeneic ” and “ allograft ” refer to cells and tissue which originate with or are derived from a donor of the same species as the recipient . the terms “ xenogeneic ” and “ xenograft ” refer to cells or tissue which originates with or are derived from a species other than that of the recipient . the present invention is directed towards a cartilage repair construct constructed of two separate pieces of allograft cancellous bone . both pieces of the two - piece allograft construct are to be derived from dense cancellous bone that may originate from proximal or distal femur , proximal or distal tibia , proximal humerus , talus , calceneus , patella , or iliium . cancellous tissue is first processed into blocks and then milled into the desired shapes . the top piece or cap member is substantially demineralized in dilute acid until the bone contains less than 0 . 2 % wt / wt residual calcium . subsequently , the resultant tissue form is predominantly type i collagen , which is sponge - like in nature with an elastic quality . following decalcification , the tissue is further cleaned and may also be treated so that the cancellous tissue is non - osteoinductive . this inactivation of inherent osteoinductivity may be accomplished via chemical or thermal treatment or by high energy irradiation . in a preferred embodiment , the cancellous cap member is treated with an oxidizing agent such as hydrogen peroxide in order to achieve a non - osteoinductive material . the bottom piece will be formed from mineralized cancellous bone or partially demineralized cancellous bone . the two piece allograft cancellous construct 20 has a base member 22 with a cap member 30 which is held fixed in place in the base member 22 by a pin . 40 . the base member 22 is preferably constructed of mineralized cancellous bone and is shaped in the form of a cylinder for easy insertion into bores cut into the patient to cut away cartilage defect areas . however , the base member 22 may be surface or partially demineralized or contain a region of cortical bone so that it is cortical / cancellous . the body of the base member 22 defines a blind bore 23 which holds a stem 36 of the cap member 30 , as further described below . the bottom surface 24 of the blind bore , as seen in fig5 - 7 , has a plurality of longitudinal through going bores 25 extending through the base member 22 and ending on the distal end surface 26 of the base member , which is preferably planar . the top surface 27 of the base member 22 is also preferably planar , forming a seat for the cap member 30 . a first lateral bore 28 extends generally transversely from an exterior wall of the base member 22 , above the bottom surface 24 of the blind bore 23 , and intersects the blind bore 23 . a second lateral bore 29 extends generally transversely from the exterior wall of the base member 22 , above the bottom surface 24 of the blind bore 23 , and intersects the blind bore 23 so as to be opposite the first lateral bore 28 ( see fig4 , 5 and 7 ) and in coaxial alignment therewith . a second plurality of longitudinal through going bores 31 are circumferentially positioned around the blind bore 23 parallel to the central axis of the base member 22 and extend from the top surface 27 to the bottom surface 26 . the longitudinal through going bores 25 and 31 have a smaller diameter than the blind bore 23 , with a diameter ranging from 0 . 5 to 2 . 0 mm . the cap member 30 has a cylindrical top section 32 which has a thickness of about 3 mm with a top planar surface 33 , an outer curved wall 34 and a bottom planar surface 35 which is seated adjacent the top surface 27 of the base member 22 when the components are mounted together . the top surface 33 while preferably planar may be milled to a degree of curvature that matches the physiological curvature of the articular cartilage being repaired , i . e ., a surface of a knee joint . larger constructs may have a cap member that has multiple stem sections and a base with an inverse “ female ” pattern which receives the stem sections . the cap member 30 includes an integral cylindrical stem 36 that depends from the bottom planar surface 35 of the top section 32 . the stem 36 has a length which is not longer than the depth of the blind bore 23 and has a diameter which is equal to or less than the diameter of the blind bore 23 . the stem 36 includes a transverse radial bore 37 which is aligned with the first and second lateral bores 28 , 29 of the base member 22 to receive a cylindrical pin 40 . more particularly , the pin 40 is inserted radially through the construct 20 to hold the cap member 30 in place within the base member 22 ( see fig3 ). the cap member 30 is preferably formed of demineralized cancellous allograft bone with a calcium content of less than 0 . 2 % calcium . alternatively , the cap member 30 has a substantially demineralized region , such as the top section 32 , with a calcium content of less than 0 . 2 % calcium . the cylindrical pin 40 is preferably constructed of cortical bone and has a length equal to or less than the diameter of the base member 22 . the pin 40 can also be constructed of a synthetic material . the cap member 30 can be secured to the base member 22 by a staple , suture , press fit or an adhesive compound such as fibrin based glue . the construct 20 is placed in a defect area bore which has been cut in the lesion area of the bone of a patient with the upper surface 26 of the cap member 30 being slightly proud , slightly below , or substantially flush with the surface of the original cartilage remaining at the area being treated . the construct 20 has a length which can be the same as the depth of the defect or more or less than the depth of the bore . if the construct 20 is the same as the depth of the bore 60 , the base of the implant is supported by the bottom surface of the bore and the top surface 33 of cap 30 is substantially level with the articular cartilage . if the construct 20 is of a lesser length , the base of the construct is not supported but support is provided by the wall of the defect area bore or respective cut out area as the plug is interference fit within the bore or cut out area with the cap being slightly proud , slightly below , or flush with the surrounding articular cartilage depending on the surgeon &# 39 ; s preference . with such load bearing support the graft surface is not damaged by weight or bearing loads which can cause micromotion interfering with the graft interface producing fibrous tissue interfaces and subchondral cysts . including the pluralities of longitudinal through going bores 25 and 31 in the construct 20 facilitates cell migration throughout the construct 20 . such cell migration promotes cartilage growth in the cartilage area and bone growth in the adjacent bone region . in operation , the lesion or defect is removed by cutting a . bore removing a lesion in the implant area . if desired , the open cancellous structure of the cap member 30 may be loaded with a cartilage paste or gel as noted below and / or one or more additives namely recombinant or native growth factors ( fgf - 2 , fgf - 5 , fgf - 7 , igf - 1 , tgf - β , bmp - 2 , bmp - 4 , bmp - 7 , pdgf , vegf ), human allogenic or autologous chondrocytes , human allogenic cells , human allogenic or autologous bone marrow cells , human allogenic or autologous stem cells , demineralized bone matrix , insulin , insulin - like growth factor - 1 , interleukin - 1 receptor antagonist , hepatocyte growth factor , platelet - derived growth factor , indian hedgehog parathyroid hormone - related peptide , viral vectors for growth factor or dna delivery , nanoparticles , or platelet - rich plasma . the construct 20 is then placed in the bore or cut away area in an interference fit with the surrounding walls . if the construct is moveable within the bore , suitable organic glue material can be used to keep the implant fixed in place in the implant area . suitable organic glue material can be found commercially , such as for example ; usseel ® or tissucol .® ( fibrin based adhesive ; immuno ag , austria ), adhesive protein ( sigma chemical , usa ), dow corning medical adhesive b ( dow corning , usa ), fibrinogen thrombin , elastin , collagen , casein , albumin , keratin and the like . the base of the blind bore 23 of the construct 20 can alternatively be provided with a matrix of minced cartilage putty or gel consisting of minced or milled allograft cartilage which has been lyophilized so that its water content ranges from 0 . 1 % to 8 . 0 % ranging from 25 % to 50 % by weight , mixed with a carrier of sodium hyaluronate solution ( ha ) ( molecular weight ranging from 7 . 0 × 10 5 to 1 . 2 × 10 6 ) or any other bioabsorbable carrier such as hyaluronic acid and its derivatives , gelatin , collagen , chitosan , alginate , buffered pbs , dextran , or polymers , the carrier ranging from ranging from 75 % to 50 % by weight . the cartilage is milled to a size ranging up to 1 mm . in the gel form , the minced cartilage has been lyophilized so that its water content ranges from 0 . 1 % to 8 . 0 %, ranging from 15 % to 30 % by weight and the carrier ranges from 85 % to 70 % by weight . the particle size of the cartilage when milled is less than or equal to 1 mm dry . the cartilage pieces can be processed to varying particle sizes and the ha or other carrier can have different viscosities depending on the desired consistency of the putty or gel . this cartilage matrix can be deposited into the demineralized cap member . the putty or gel enhances the tissue integration between the plug and host tissue . it is also envisioned that demineralized bone matrix and / or growth factors such as ( fgf - 5 , fgf - 7 , igf - 1 , tgf - β , bmp - 2 , bmp - 4 , bmp - 7 , pdgf , vegf ) or soluble factors such as insulin , interleukin - 1 receptor antagonist , hepatocyte growth factor , indian hedgehog and parathyroid hormone - related peptide , viral vectors for growth factor or dna delivery , nanoparticles may be adsorbed or combined with the construct or the cartilage pieces . in another embodiment , platelet - rich . plasma may be added to the construct . it is also envisioned that cells which have been grown outside the patient can be inserted by syringe into the cancellous cap member 30 before , during or after deposit of the construct 20 into the defect area . such cells include allogenic or autologous , bone marrow cells , stem cells and chondrocyte cells . the cellular density of the cells preferably ranges from 1 . 0 × 10 8 to 5 . 0 × 10 8 or from about 100 million to about 500 million cells per cc of putty or gel mixture . the cap member 30 can support the previously mentioned chondrogenic stimulating factors . the principles , preferred embodiments and modes of operation of the present invention have been described in the foregoing specification . however , the invention should not be construed as limited to the particular embodiments which have been described above . instead , the embodiments described here should be regarded as illustrative rather than restrictive . variations and changes may be made by others without departing from the scope of the present invention as defined by the following claims :	0
the present disclosure relates to systems and methods which can increase the recovery rate of fresh water from otherwise undesirable water , as well as provide additional uses for the by - products and / or wastewater of such systems and methods . one skilled in the art will appreciate that various aspects of the disclosure may be realized by any number or type of structures and systems , as well as various types of undesirable water . for example , much of the present disclosure finds utility in the desalinization of seawater . however , one skilled in the art will appreciate that other water which has varying contaminants may likewise be found to be treatable in accordance with the present disclosure , and as such , this disclosure should not be considered to be limited to desalination alone . moreover , while various membranes and filtration materials may be disclosed herein , those skilled in the art will appreciate that depending on the applications at hand , alternative materials , membranes , filters , and the like , as well as other structures , may likewise be suitable and fall within the scope of the present disclosure , even where not expressly recited . it should also be noted that the drawings herein are not all drawn to scale , but may be exaggerated to illustrate various aspects of the disclosure , and in that regard , the drawings should not be limiting . additionally , those items disclosed herein may be described herein in terms of functional block components , optional selections and various steps . it should be appreciated that such functional blocks may be realized by any number of components configured to perform the specified functions . the present disclosure provides various levels of increased fresh water recovery percentages above those presently attainable by current ro only technology . specifically , by integrating existing ro technology and systems with forward osmosis ( fo ) technology and nanofiltration ( nf ) technology , such recovery increases are attainable . in this regard , by combining the optimal performance properties of multiple technologies in a particular order , for example , ro , nf , and fo , such recovery increases may be obtained . in other words , by exploiting the best characteristics each of ro , nf , and fo , the inherent ceiling of ro can be improved , with recoveries well beyond ros thermodynamic limit of 1 . 8 cycles of concentration . such integration is referred to herein as “ integrated osmosis ” or “ io .” for example , a comparison of conventional two - pass swro to io is shown in table 1 below . as disclosed herein , io contemplates a process of providing additional freshwater recovery and a decreased volume of high total dissolved solids ( tds ) concentrate ( or wastewater ) from conventional freshwater extraction processes ( hereinafter , for simplicity , referenced as reverse osmosis or ro regardless of the type of freshwater extraction technology ). io affords these benefits by effecting a staged osmotic separation process , specifically , nf with specifically developed and selected morphology and zeta potential ( which may include one or more sw nf filtration structures or stages ) and , optionally and as described below , a very low energy nf stage , which prefaces a fo process upon the wastewater concentrate stream of a conventional ro system . the io process also provides a means to extract freshwater from other high tds concentrate feed waters which are otherwise intractable by the prior art . more specifically and as described in additional detail herein , with reference to fig1 , an io system may comprise a conventional two - pass sea water reverse osmosis ( swro ) stage 100 passing through a “ fence line ” 101 , a conditioning stage 110 where conditioning of swro concentrate ( e . g ., having a concentration of 58 , 000 ppm ) from the swro stage 100 occurs , for example , to reduce calcium , and an additive stage 115 where various additives may be added to the conditioned concentrate ( e . g ., surface tension lowering additives , etc .). after the additive stage 115 , as described below , a selective nf stage 120 processes the conditioned swro concentrate to remove certain ions , with about 72 % recovery rate of nf permeate , and about 23 % concentrate which can proceed to a byproducts harvesting stage 160 to harvest materials which may be used in other applications ( e . g ., concentrated brine solution which may be used in solvay process , soda ash , etc .). the sw nf permeate may then , as described in more detail below , optionally pass through a very low energy nf stage 170 ( vlenf or “ ultrafiltration ” or simply “ uf ”) and / or a weak base anion exchange ( wba ) stage 180 ( e . g ., bicarbonate hco 3 form ) to form a uf concentrate , or alternatively , may move directly to a fo stage 130 . the wba stage 180 acts as a carrier for a metallic bioenzyme toggle for h 2 co 3 and h 2 o and co 2 . in the event the sw nf permeate first goes through the vlenf 170 or wba 180 stage , the concentrate from these stages may be used in as draw solution osmolyte in the fo stage 130 . the fo stage 130 may see a recovery rate of about 80 %. after the fo stage 130 , a final separation osmolyte stage 140 may also be employed , providing about 95 % permeate recovery rate with an end use water output having less than about 150 tds . the remaining draw solution osmolyte from the final separation stage 140 may optionally be further processed in an additional purification stage 150 , if necessary . in accordance with another embodiment of an io system and with reference to fig6 , of note , the illustrated io system does not refer to swro elements , high pressure pumps , a compact skid , or energy recovery equipment . rather , the illustrated io system uses thermodynamics of mass and heat transfer , a catalytic performance of a metallic bioenzyme , and waste heat available at the source , or other economical means ( e . g ., thermal fluid , dmso and thermolytic nanoparticles ). the io system begins with seawater taken though a nf stage ( swnf ), with a pretreatment goal to reach a sdi value below 3 . 0 and turbidity below 0 . 2 ntu . at this point , the feed 690 and is processed through a sw nf stage 600 to selectively reject more than 70 % calcium , more than 80 % magnesium , and more than 90 % sulfate ions while passing as high a percent of monovalent ions as possible . a term defined as relative apparent molar enthalpy captures the value of an exotherm as a beneficial heat source as heat of dilution in kj / mol . multiply by total mols of dmso or libr to obtain the total heat . commercially available swnf membranes from ge water and dow ( filmtec ) are exemplary membranes which may be modified and used in accordance with the present disclosure . as illustrated in fig6 , using two stages of fo 610 a , 610 b , the mass transfer of water to the draw solute is maximized . additionally , the illustrated io system takes advantage of an almost eight - fold difference in osmotic pressures between osmolyte a 620 a , 620 b , as well as factors such as permeate suction , temperature , and the like . as those skilled in the art will appreciate , osmotic pressure is the pressure required to stop the process of osmosis . in other words , water moves down to its osmotic potential . moreover , the influential metallic enzyme lowers the pka of water from 15 . 7 to 7 . fo concentrate from nf stage 610 a is feed water to nf stage 610 b . the higher the fo retentate , the higher the recovery yields from ro 630 . by way of comparison , conventional two - pass swro gives a recovery of about 42 % and sec ( with erd ) is about 3 . 8 kwh / m3 . in contrast , the process illustrated by fig6 shows a recovery greater than 80 %. additionally , as described in further detail below , in accordance with the present disclosure and with reference back to fig1 , io employs nanofiltration of the high tds concentrate feedwater as a first stage , prior to any fo stages . in contrast to ro , wherein nearly all ions are removed from the feed water , the nanofiltration first stage of io selectively removes only a certain population of ions . for example , non - monovalent ( e . g ., divalent , trivalent , etc .) ions are preferentially removed with minimal effects upon monovalent ions to produce a lowered osmotic pressure solution . the removal of non - monovalent ions reduces scaling tendencies promoted by bonding with sulfates , carbonates , silicates and the like . an additional benefit is removal of fine and colloidal solids . the nf stage generates water that is essentially free of suspended solids and has a stable ph , offering a lowered osmotic pressure afforded by the reduced non - monovalent ion concentration . this water proceeds to the next stage process of io which incorporates one or more fo stages benefitting from the reduced osmotic pressure and a negative charge provided by the earlier stage of io . in accordance with various aspects of the present disclosure , by employing io with concentrate produced from ro , additional freshwater recovery can be achieved , a net benefit overall . benefits of io as contemplated herein include the ease of installation and “ retro - fitting ” to existing ro processes . in this regard , io processes can be readily added as a “ bolt - on ” type configuration , affording increased freshwater production using the combined processes . increased freshwater recovery from the combined existing ro and the nf and fo processes thus offer enhanced use of invested capital and infrastructure of the existing ro system &# 39 ; s intake , discharge and pretreatment associated processes . for example , in io retro - fit cases , where an existing ro process results in a 42 %/ 58 % freshwater / concentrate split , by increasing the daily freshwater product output by 50 percent of the feed ( 0 . 51 × 58 , 000 m3 / d =˜ 30 , 000 m3 / d ) using io , results in a about 70 % increase of freshwater recovery . this mass balance also allows a complete use of all the pretreatment ultrafiltration capacity and a modular design leaves space to accommodate adding more surface area for expansion . a io process can therefore complement the objective of adding more uf capacity ( with the hardware in place ) by inserting cassettes or modules with membrane area ( software ). additionally , there is a corresponding reduction in the volume and disposal cost of concentrate being discharged inland or in the ocean . in this regard , because io affords an increase of freshwater production and a concurrent decrease of waste concentrate volume , a further benefit is the reduction of waste concentrate and associated handling and disposal costs . this benefit also provides an additional object of io , namely , volumetric waste reduction lessens “ zero liquid discharge ” ( zld ) processing costs rendering zld environmental and / or regulatory goals more affordable ( see for example , fig6 ). moreover , if the waste concentrate tds level can be elevated to a high enough level ( e . g ., 230 , 000 ), there is no need to a crystallizing step or related apparatus , and rather , all that is needed is an evaporator , saving further capital cost . further still , licensing and permits for incremental expansion of existing ro systems may be straightforward and less cumbersome to obtain and implement , thereby bringing additional capacity on - line in less time . additionally , io generally does not require additional expensive , long lead time , high pressure swro pumps . moreover , io provides a higher and more efficient utilization of the treated feed water of an existing ro system , and higher salts content in the concentrate provide additional options for valuable by - product salt or mineral extraction , which may also be capable of reuse in the io process itself . examples of such by - products include concentrated , very high purity (& gt ; 99 %) brine which may be usable as feedstock for solvay processes . the same may also provide flexibility to convert various nanofiltration concentrates into sodium sulfate as a draw solution ( osmolyte ) for fo processes . additionally , in the united states for example , inland desalination would be a much needed and appreciated pathway for treating brackish water ( 3 , 000 ppm to 12 , 000 ppm tds ) were it not for the prohibitive concentrate disposal cost . depending on the mode of disposal , this cost can vary from about $ 3 . 5 mm per mgd to $ 12 mm per mgd . estimates put these high tds water / s in the state of texas alone at about 2 . 5 billion acre feet or about 830 trillion gallons . as such , an io process such as disclosed herein , offers the potential of affordability for use of this water as a source for potable and industrial needs . additionally as discussed in more detail herein , in regions or water bodies where the threat of habitual algae toxins ( hab ) puts the entire desalination system in a total shut down mode or operate with a risk of severe fouling of swro membranes , an io system such as disclosed herein , if installed with a disc filtration system like the integra ® system consisting of discs ranging in micron size from 200 microns to 2 microns with discs made of a blend of robust plastics along with the dissolved air filtration ( daf ) system from the original swro system can be programmed to work congruently to prepare the feed for the io system . thus , in times of hab , if the decision is made to operate the swro system due to need and no alternate resource of drinking water nearby , then the sw feed is taken past the intake screen infrastructure , then the daf system , then through the integra ® disc filtration system and then through the io system ( by - passing the two - pass swro system ). additionally , seawater nf has zwitterionic properties . therefore , lowering the ph to the iso - electric point and changing the zeta potential from minus ( 15 mv to 25 mv ) to neutral , along with addition of a food grade humectant bacteriostat , plus permeate suction , prevents buildup of a concentration polarization gradient adjacent to the nf membrane skin layer . in various embodiments , the fo membrane may have a contact angle below 60 degrees and the substrate osmolyte draw solution can be blended to keep the substrate continually moist , thus minimizing bacterial accumulation on the membrane skin layer . operating levers like osmotic backwash , permeate suction , and keeping the draw cross velocity higher than the feed velocity ( net cfv or cross flow velocity ) can also minimize biofouling or hab accumulation . those skilled in the art will appreciate that fo has many characteristics that are similar to ro , including fouling or plugging from suspended solids ( tss - total suspended solids ), osmotic pressure effects exerted by dissolved solids ( tds ), bacterial contamination and associated bio - fouling , contamination and fouling by natural organic materials ( nom ) as well as fouling from oil and grease . in contrast to ro , these characteristics and associated difficulties effect and interact with both the feed water and the draw solution sides of forward osmosis membranes burdening fo with additional and unique characteristics and difficulties . thus , until the present disclosure , fo was oft - ignored by those skilled in the art . in this regard , io is novel and counterintuitive in that it uses nf before uf and fo . by operating the nf process in a 2 × 1 array ( see fig2 for example ) with the first array consisting of a hydrophilic nf membrane operating at a ph of 3 . 0 to 3 . 5 , calcium removal can be maximized . the second array can operate at a ph above the iso - electric point to maximize rejection of sulfate ion and magnesium ion . additional nf membranes may be added to the io system as desired . for example , fig3 illustrates a three - stage nf process . by having a nf step before the fo step , the skin layer roughness and the cross linkage of the amide group relative to the linear pendant carboxylic acid groups can be maximized . this is beneficial in that increasing the amide linkage also increases hydrogen bonding sites and thus , osmotic permeability of water molecules through the fo membrane is accelerated , capitalizing on this feature of the fo membrane , namely , that it has the best mass transfer of water facilitated by the performance of the nf membrane rejecting divalent ions , suspended solids , nom and biofoulants . by focusing the nf step more exclusively on rejecting a large percentage of non - monovalent ions and sub - micron suspended solids , the nf membrane will pass monovalent ions , operate at moderate hydraulic pressure , and reduce the osmotic pressure on feed side of the fo process . thus , nf recovery can reach a range of about 75 % to about 80 %, and importantly , removal of calcium by nf allows raising the molar concentration or tds driven osmotic pressure of the draw solution in fo and allows fo to operate at high recovery rates , often greater than about 70 %, and approaching about 80 %. a result from fo is thus a maximizing of the mass transfer of water from the feed side to the draw side in a relatively more compact footprint . in various embodiments , the use of “ operating levers ” available can help facilitate , catalyze , humectize , reduce surface tension reduction , turbulence promoters , thermal enablers to accelerate transport phenomena and water transport . while this can increase operating expenses , because of the increases in recovery and other benefits noted above , including the reduction of footprint and capital expenditures of forward osmosis , the returns are significant . in accordance with various aspects of the present disclosure , both nf and fo elements can be manufactured in a “ full fit ” construction ( no fiber glass exterior and no brine seal ) for efficient osmosis . urethane glue can be applied in a “ w ” pattern in spiral wound fo elements thereby improving robustness and increasing available surface area . additionally , the layout of the fo elements may be placed in a parallel design ( longitudinally ) wherein each element is encased in its own cartridge housing providing increased cleanliness and economy , as well as the capability to maintain a substantially constant difference in pressure on feed and draw sides , allowing more uniform flux . in accordance with various embodiments , varying blends of different draw solutions / osmolytes may enable operating fo in either an active layer facing feed ( al fs ), solution diffusion first , convection second mode when the draw solution or osmolyte is mostly inorganic , or an acting layer facing draw ( al ds ), convection first , solution diffusion second mode when the osmolyte is mostly organic . as noted above , in accordance with various aspects of the present disclosure , io may use a metallic bioenzyme that provides a basis for deprotonation of water by lowering the pka of water from 15 . 7 to 7 . by virtue of this decrease , more water molecules are available to deprotonate at a lower ph to turn into hydroxyl ion , a better nucleophile . with reference briefly to fig7 , illustrating a flow diagram of a validation of a pilot demonstration using an integrated osmosis system as contemplated herein . the scalability of the pilot demonstration of 1440 gpd is about 500 : 1 — can go up to as 750 , 000 gpd . in accordance with various aspects of the present disclosure and with reference back to fig1 , a first step of io includes conditioning and pre - treatment 110 of the initial feed water ( e . g ., high salinity seawater concentrate ) from a conventional two - pass ro process 100 . a conventional two - pass swro has a feed salinity of about 33 , 000 ppm , a permeate tds of about 250 ppm and has a recovery rate of about 42 % with about 3 . 9 sec kwhr / m 3 . for io , the feed salinity is about 65 , 000 ppm , permeate tds is less than about 100 ppm and has a recovery rate of about 51 % with about 5 . 8 sec kwhr / m 3 . while the composition of tds in a swro concentrate is generally consistent throughout the year , frequent analysis of residuals in the concentrate like antiscalant degradation products , biocides , nom and recently reported leucothrix mucor and rugeria species is desirable . for example , analysis of a typical seawater concentrate sample is as follows : dependent upon the point of discharge of the concentrate and the re - entry as feed to an integrated osmosis process , there may be a presence of iron , bio - available manganese ( for example , as high as 230 ppb in the indian ocean ) to form ferromanganese blooms , dissolved organic matter , tep ( total exopolysaccharides ) and algae . as such , pre - treatment 110 may be important . as noted above , calcium is addressed first because of the potential difficulty of calcium complexing with nom and the potential of calcium sulphate precipitation dependent upon the state of calcium ( e . g ., dehydrate , hemihydrates and anhydrite ) and temperature . solubility of caso 4 @ 0 . 015 % molal is the highest at 30 ° c . thus , a chelating compound is used to bind calcium and trace levels ( e . g ., ppb ) of ferro - manganese bio foulants . exemplary chelating agents include , ethylenediaminetetraacetic acid ( edta ) and nitrilotriacetic acid ( nta ) though others may likewise be used . for example , alternate “ green compounds ” such as the tetra sodium salt of glutamic acid / n , n diacetic acid ( dissolvine gl 36 ) may be preferable . additionally , during “ red tide ” season ( or habs , as noted above ), suspended fine solids , red algae , algal cells ( 10μ to 15μ ), bacteria ( 1μ to 2μ ), aom ( algogenic organic matter ) and particulate matter (& lt ; 0 . 45μ ) can become ubiquitous . thus , an effective ( and often inexpensive ) adsorbent bed of hydrophilic polysulfone with chitosan and cloisite a 30 b media installed . this bed has a nominal pore size of about 3 microns . following this bed , an integra disc filter system ( high surface area and 26 , 000 linear feet depth per module ) alongside a smart sponge plus to provide adequate residence time or ebrt ( empty bed retention time ) to yield an effluent with sdi below 2 . 5 and turbidity below 0 . 2 ntu . additionally , these disc filters can be backwashed and are made of oleo phobic and hydrophilic engineered polymers . additionally ( or alternatively ), in various embodiments , to minimize calcium sulfate dehydrate scaling , a 1 : 1 ratio of a blend of two antiscalants , for example , polyacrylic acid and polyether polyaminophosphonic acid can provide about 80 % inhibition of calcium scaling . additional food safe additives , surfactants , and the like , may be added to the pretreated swro concentrate in stage 111 to lower surface tension and to end cap the unreacted monomers in order to minimize reverse salt flux or theft of ‘ a ’ value of a fo membrane from unreacted amine leaking through . by using a super spreader surfactant ( e . g ., siloxane polyalkyleneoxide such as silwet ® 77 or silwet ® 78 ) an improvement in the fo membrane &# 39 ; s hydrolytic stability vs . ph can be obtained . additionally , a lower amount of surfactant , namely about 0 . 15 wt . % instead of the more conventional 2 . 0 wt . %) required results in an even , homogeneous spread across the width of the membrane flat sheet in manufacturing . in accordance with various aspects of the present disclosure and with reference to fig1 , 3 and 6 , a second step of io includes nf 120 of high salinity seawater concentrate . nf covers the bandwidth between about 15 ° a to about 115 ° a and typically operates in a pressure range of about 40 psig to about 200 psig ( in sw sr applications ). in various embodiments , the non - monovalent ions are organic molecules with competitive osmotic pressure . in other embodiments , the non - monovalent ions are positively charged inorganic molecules . as mentioned above , in various embodiments , nf rejects non - monovalent ions such as sulfate , calcium and magnesium , and can also reject micron - sized suspended matter such that a very high percent of monovalent ions pass through to the fo process . removal of non - monovalent ions proceeds at a slower diffusion rate , resulting in a lower molar flux . however , the fo membrane is advantaged because the feed is homogeneous , accelerating the mass transfer of water . for example , rates of greater than about 95 % rejection of sulfate , greater than about 85 % rejection of calcium and magnesium can be obtained . single stage ( fig1 ), two stage ( fig2 ), three stage ( fig3 ) or more nf membranes may be used . an exemplary nf membrane is manufactured by ge water , and is known as swsr 400 ( 400 square feet area ). those skilled in the art will recognize that other nf membranes may also be used and still fall within the scope of the present disclosure . by using nf before fo , numerous benefits may be achieved . for example , the hydrated ionic radii of divalent ions diffuse slowly across the membrane skin layer interface resulting in a lower molar flux , proceeding at a rate to maintain electro neutrality . for example , hydrated ionic diameter of magnesium is 16 ° a while potassium is 6 ° a . additionally , a lower tds feed to fo means lower osmotic pressure . the nf rejection of any trace turbidity in the feed , gives flexibility in construction of the spiral wound fo element with respect to spacer thickness and permeate tricot fabric . moreover , permeate from nf has a negative zeta potential as it approaches the fo boundary layer . this will catalyze higher rejection of monovalent ions and lower reverse salt flux . further , the reject from nf can easily be converted to sodium sulfate ( na 2 so 4 ), giving a good osmolyte or draw solution at an economical and environmentally responsible cost . additionally , when the feed to the fo process is mostly monovalent ions and the draw solution is non - monovalent , the reverse salt diffusion is lower than the vice versa condition . because the osmotic pressure “ load ” in a nf membrane is primarily divalent and under 325 psi , a pathway is cleared to build the nf elements in a non - fiber reinforced polyester ( frp ) full fit construction without a brine seal . a further benefit is a lower pressure drop per element , a higher cross flow velocity , no biofilm growth and more room to pack more surface area . in various embodiments , permeate suction may be applied to keep the boundary layer destabilized and decrease concentration polarization , while at the same time increasing the mass transfer coefficient . the role of permeate suction in mass transfer through porous membranes is important as it enhances mass transfer from the bulk to the membrane surface . by applying suction at the end of the collector tube of the membrane module , an increased rate of pressure will be present . this ill destabilize the boundary layer at steady state conditions . permeate suction changes the solutions physical properties , such as viscosity , density and diffusivity — all functions of concentration . in accordance with various aspects of the present disclosure and with reference to fig1 , an optional third step of io may include uf stage 170 and / or wba 180 of the nf permeate . for example , permeate from nf as described herein may have more than 12 , 000 ppm of sodium and even more chloride . by installing a uf membrane with 0 . 5 nm pores and with sodium dodecyl benzene sulfonate adsorbed on the membrane , sodium complexed with chloride will show rejection up to about 50 % at a maximum loading of 0 . 05 mmols / gram while sodium complexed with sulfate shows a rejection of about 75 %. as noted above , a wba stage 180 acts as a carrier for a metallic bioenzyme toggle for h 2 co 3 and h 2 o and co 2 . in accordance with various aspects of the present disclosure and with continued reference to fig1 , and 6 , a fourth step of io includes a fo stage 130 / 140 / 615 a / 615 b . in the presently described example , swro concentrate going through the io system as a feed to the nf step has a tds of about 66 , 000 ppm . the swnf permeate has a tds of about 40 , 000 ppm as a feed to advanced uf step . the uf permeate has a tds of about 30 , 000 ppm and is fed to the fo step . at the fo stage 130 , with a feed of about 30 , 000 ppm , the osmotic pressure will be about 300 psi . briefly , with reference specifically to fig5 , the relationship between advection ( cross - flow velocity ), convection ( temperature ), and diffusion ( suction ) is shown . of note , the flux of a draw solution solute through a support layer in a fo membrane is equal to the sum of diffusive and convective components of flux . when the feed concentration is greater than about 0 . 5 m , more permeate suction may be applied to improve diffusivity . if temperature is raised , this may mitigate some effects of dilute internal concentration polarization gradient ( dicp ). with respect to fo membranes , the boundary layer thickness is inversely proportional to the square root of the peclet number . in an embodiment , an exemplary guideline for a balanced operation of a fo system with feed side concentration below 0 . 5 m ( about 29 , 000 ppm tds ) is as follows : 1 . feed and draw are countercurrent . 2 . in a thin film composite polyamide fo membrane , the cfv of draw is higher than the cfv of the feed . ( e . g . 25 cm / sec to 15 cm ) 3 . the draw solution concentration should be between 2 × to 3 × of the feed concentration . 4 . take advantage of heating the draw solution to 45 ° c . and also keep the feed at a constant temperature to avoid temporal variation and its impact on flux . 5 . situating the fo elements longitudinally in individual cartridges in a full fit design offers the ability to maintain a constant gap or gradient between the feed and the draw . in a conventional latitudinal arrangement of fo elements in a pv , the fo feed gets more concentrated while the ds moving in opposite direction is picking up more water , becoming more dilute and thereby decreasing the gap or gradient between the feed and the draw . when this happens , less water is drawn from the feed side , counter to the objective of fo . 6 . osmotic backwash and permeate suction help assure consistent performance of the fo system . 7 . high ionic strength ds may de - swell a cellulose triacetate fo membrane via charge neutralization which results in lower water permeability and higher salt passage and lower structural parameter . this trend may be exacerbated by the presence of divalent cations which tend to swell the polymer . though de - swelling is not as much of an issue in membranes made by interfacial polymerization , this is another reason to put sw nf before fo . 8 . de - swelling at high osmotic pressures leads to osmotic dehydration . 9 . in the al fs mode , the ds penetrates the porous support layer to the interior surface of the active layer before flux can occur . preferably , fo elements are shipped wet from the manufacturer in a preservative such as peg400 . in various embodiments , io the fo stage 130 may comprise a fo thin film composite membrane optimized for particular performance characteristics , such as maximizing the mass transfer of water from the polyamide skin layer to the substrate by allowing a two phase flow or simply bubbling high quality carbon dioxide gas through the feed solution . the fo membrane may be a carrier for a metallic bio - enzyme which is very fast and efficient in catalyzing formation of h 2 co 3 or carbonic acid and liberation of protons ( h 2 o + co 2 —←→ h + hco 3 ). by manipulating the zeta potential , the membrane is maintained as the transporter . the fo membrane may have a backing . for example , in an embodiment , the backing may be a tricot material , similar to what may be used to make a permeate channel tricot in spiral wound nf and ro membranes . alternately , a woven 2 . 7 mils thick , 70 microns in thickness may be used . the fo may also have a substrate . because cyclic dimer is an impurity and can makes a solution cloudy , low cyclic dimer ( lcd & lt ; 1 . 5 wt . %) grade of polysulfone may be included with a desiccant to assure no humidity or moisture enters the holding tank where polysulfone / solvent are kept before deposition on the casting line ( phase inversion process ). additionally , 5 micron and 1 micron cartridge filters may be provided to filter the polysulfone dope before deposition on the web . to obtain a narrower pore size distribution with high pore density and smaller interconnected pores , a hydrophobic surfactant may be added to the polysulfone dope before phase inversion and keep the coagulation tank temperature at 5 ° c . an effective fo membrane facilitates active mass transfer of water from the thin film composite layer to the uf substrate . this active role collaborates with the draw solution for an optimal mass transfer of water . this is achieved by maximizing the population of network pores ( 1 angstrom to 5 angstroms ) in the membrane skin layer and by using a super hydrophilic surfactant in the feed . residual acid chloride groups catalyze breakdown of amide functionality as h + ion availability is reduced . while it is common practice in interfacial polymerization process for brackish water ro membranes to use as much as 6 wt . % mpd ( amine ), the optimal amount for fo membrane is 2 wt . %. using analytical tools such as positive annihilation lifetime spectroscopy ( pals ) and quasi elastic neutron scattering ( qens ), it is known that the aggregate pores and network pores can have a variety of pore structures . the dynamics of movement of water in the polymeric membrane is best described as jump diffusion . in accordance with various embodiments , the functionality of io , and specifically the fo stages of io , is illustrated in table 2 below , comparing the functionality and the relative importance , and ranking the same : mass transfer of water through fo membranes is moderated by diffusion , particularly on the draw solution side of the fo membrane . osmolyte diffusion toward the reject layer of the membrane generates the osmotic pressure gradient necessary for mass transfer . diffusion may influenced by many factors or variables , temperature typically being the most significant and direct influencer . complementing this variable is the stability of thin film composite polyamide and to a degree , cellulose tri acetate membrane and element morphology . the increase in permeability and flux when temperature is increased is notable . for example , flux increases by almost 40 % when the temperature rises from 20 ° c . to 40 ° c . however , the cost of energy should be considered when analyzing the cost / benefit analysis of the thermal benefits . additionally , the advent and successful development of nanofluids as an enabling and increasing the efficiency of heat transfer medium may change the economic calculations of operating costs of fo . for example , nanofluids such as aluminum oxide and titanium dioxide are excellent choices as enablers for heat transfer , with titanium dioxide better than aluminum oxide . in accordance with various aspects of the present disclosure and with reference to fig1 and 6 , a fifth step of io includes separating a draw solution ( osmolyte ) in a final separation stage 160 . in the presently described embodiment , a dilute draw solution ( mixture of inorganic salt ) or osmolyte mixture is rejected by a high rugosity , high porosity , 0 . 5 nm pore size membrane , such as filmtec nf 90 . typical rejection is more than 99 . 5 %. additionally , to obtain additional rejection at low energy , a surfactant ( e . g . sodium dodecile benzene sulfonate ) charged uf ( about 3 nm pore size ) membrane at critical micelle concentration ( cmc ) may be used for rejecting sodium . io processes as contemplated herein provide incentives to various public interest groups and private sectors working towards the goal of achieving zero liquid discharge for a cleaner environment . in this regard , the applicability of io processes cover a wide bandwidth of waste waters with suspended and dissolved solids as well as other organic contaminants . for example , current practice globally is to re - inject the concentrate at twice the feed salinity back into the ocean . however , numerous studies done by various research groups show the adverse impact higher salinities have on marine life . as such , in accordance with various aspects of the present disclosure and with reference to fig8 , an example from a seawater desalination process using reverse osmosis membranes is illustrated , addressing some of these impacts . in sum , the io process accomplishes the following results : 1 . reduces the volume of water — by increasing the tds in swro concentrate to a tds range of 180 , 000 ppm to 230 , 000 ppm , the net volume to be handled by an evaporator and crystallizer stay small in size and affordable . 2 . little or no concentrate needs to go back in the ocean . 3 . significantly reduces the total cost of sea water disposal of the concentrate . 4 . reduces carbon footprint . 5 . if by - products do find their niche application ( like brine ) for most of the year , this further reduces waste . 6 . na 2 so 4 can also be made as a byproduct from the nf concentrate . last , the foregoing disclosure is illustrative of the present disclosure and is not to be construed as limiting the disclosure . although several embodiments of the disclosure have been described , persons of ordinary skill in the art will readily appreciate that numerous modifications could be made without departing from the scope and spirit of the disclosure . as such , it should be understood that all such modifications are intended to be included within the scope of this disclosure . the written description and drawings illustrate the present disclosure , and are not to be construed as limited to the specific embodiments disclosed .	2
referring to fig1 , there is shown in perspective view a putter 1 with a scale 10 mounted to the putter shaft 2 . the shaft 2 includes a lower end 2 a that is connected to the putting head 4 , e . g . via a hosel . the upper end 2 b of the shaft 2 receives a grip 7 . referring to fig2 - 3 , the scale 10 indicates the degree of slope to a green by utilizing a pair of weighted ends 15 a , 15 b of a balance arm 14 configured to freely rotated about a shaft assembly 30 . the degree of movement of the arm 14 is appreciated by inspecting the deviation of the arm 14 relative to a fixed reference line 18 formed on the front surface of a backboard or reference surface 30 , the scale 10 may be enclosed in a glass or plastic case 11 . the case 11 may be formed as a diverging convex lens , which magnifies the relative positioning between the arm and reference line 18 for ease of viewing by the golfer . when the putter 1 is placed on the putting surface in the manner shown in fig2 , i . e ., with the reference line 18 extending parallel to the slope of the green and the rotation axis a ( see fig3 b ) orientated substantially perpendicular to the vertical , the arm 14 will rotate clockwise or counter clockwise if the slope of the putting surface is at an angle to the horizontal . the degree of slope may then be understood by the angle θ between the reference line 18 and the arm 14 . regardless of the tilt or slope of the putter , the arm 14 will extend parallel to the horizontal when the arm 14 is balanced about its support point 20 . thus , in fig2 the scale 10 indicates the degree of slope of the putting surface based on the difference between the horizontal ( arm 14 orientation ) and the slope of the green ( reference line 18 ). the difference in degree of slope being indicated by the angle θ between line 14 and line 18 . in some embodiments , this perturbation or rotation may be expressed visually to the golfer by simply inspecting the relative locations of the lines 14 , 18 , by using reference hash marks or reference lines displayed across the surface 30 or placed on the glass / plastic cover 11 , or by using distinguishing colors or patterns ( see fig6 a - 6b ). according to another aspect of the disclosure , the scale 10 includes a locking feature that enables a golfer to pick up the putter to inspect the slope depicted on the scale 10 . referring to fig4 a - 4b , which shows a cross - sectional view of the scale 10 as in fig3 b , the scale includes a shaft 20 about which the arm 14 pivots . the shaft includes a head 21 , a lower end having a knob 24 and a fitting 2 e that allows shaft to be pulled and pushed up or down , as indicated in fig4 a - 4b . when the knob 24 is pushed upwards as shown in fig4 a , the head 21 is separated from the surface 30 and does not obstruct the rotation of the arm 14 , so that the arm 14 can freely rotate about the shaft 20 . when the head 21 is brought down to abut the surface 30 , as indicated by reference 23 in fig4 b , the head 21 is pulled into abutment with the surface 30 and arm 14 , thereby retraining free rotation of the arm 14 . the knob 24 may be easily pressed towards the shaft opening 2 e , or pulled away from the shaft opening 2 e to selectively engage / disengage the head 21 from the arm 14 by known methods in the art , e . g ., by having a resilient , plastic ledge that engages with a ridge formed on the shaft 26 that selectively positions the head 21 in the locked ( fig4 b ) or unlocked position ( fig4 a ). this locking feature enables a golfer to pick up the putter to inspect the slope indicated on the scale 10 without disrupting the relative position between the arm 14 and reference line 18 . in use , the golfer would first place the putter 1 on the ground in the manner shown in fig2 ( so that the rotation axis a is about perpendicular to the vertical ) and allow the arm 14 to come to rest . next , the golfer would pull the knob 24 out ( fig4 b ) so as to fix the arm 14 in its balance position relative to the reference line 18 . the golfer may then pick up the putter to visually inspect the position of the arm 14 relative to the line 18 . this locking feature can obviate the need for a golfer to have to bend down to an uncomfortable position in order to inspect the scale 10 . referring to fig6 a - 6b , according to some embodiments , the scale 10 may include hash marks 40 that can be used to inspect the degree of slope , i . e ., the amount that the arm 14 has rotated relative to the reference line 18 . according to other embodiments , a scale 50 includes arms 14 which have a first color 52 and are shaped to cover a second color 54 when the putting surface is flat ( fig6 a ). when the putter 1 is placed on a sloped surface ( fig6 b ), the arm 14 having a first color 52 surface rotates to expose the second color 54 . the first color 52 may be , for example , green and the second color 54 red . while particular embodiments of the present invention have been shown and described , it will be obvious to those skilled in the art that changes and modifications can be made without departing from this invention in its broader aspects . therefore , the appended claims are to encompass within their scope all such changes and modifications as fall within the true spirit and scope of this invention .	0
in accord with the present invention , it has been unexpectedly found that the presence of an omega - 6 acid component , comprising either the free acid or a derivative thereof such as an ester or the like (“ omega - 6 acid component ”), will inhibit the isomerization of 17 - substituted hydrocortisones and other steroid materials . the present invention has particular utility in the stabilization of hydrocortisones having an ester moiety at the 17 position , and is particularly useful in stabilizing hc17 - b , and will be described with particular reference to the stabilization of hc17 - b . there are a variety of omega - 6 acids which function to stabilize the substituted hydrocortisones . “ omega - 6 ” signifies that the first double bond in the acid , counting from the end opposite the acid group , occurs in the sixth carbon - carbon bond . there is some confusion due to the fact that there are various nomenclature and numbering systems used for fatty acids . hence materials of the present invention have been referred to as “ omega - 3 ” acids , as well as by other names . in any event , within the context of this disclosure , the foregoing definition of omega - 6 acids is utilized . linoleic acid , also known as 9 , 12 - octadecadienoic acid , is one omega - 6 acid having utility in the present invention . linoleic acid is generally a very safe material , and is readily available . safflower oil is a triglyceride , comprising a fatty acid ester of glycerol , and it contains large amounts of linoleic acid in esterified form , and in particular embodiments of the present invention , safflower oil is used as a stabilizing agent for hc17 - b and similar materials . safflower oil is particularly advantageous for use in pharmaceutical compositions , since it is generally nontoxic , and has been approved for both topical and internal formulations . additionally , safflower oil , as well as other omega - 6 acid materials , have additional beneficial effects in topical formulations since they can enhance skin penetration and restore lipid content to the skin . other omega - 6 acids include arachidonic acid . yet other polyunsaturated omega - 6 acids are known in the art . such omega - 6 acids , as well as their esters and like compounds , may also be used in the present invention . in general , the omega - 6 acid component will be present in an amount which is at least equimolar with the steroid compound which is to be stabilized . in most practical formulations , the omega - 6 acid component is present in a relatively large excess , since it further functions as a skin conditioning agent . for example , it may be present in a weight percentage ten , twenty , thirty or even more times the weight percentage of the steroid compound . two experimental hydrocortisone 17 - butyrate formulations were prepared . one ( formulation r6546 ) contained a substantial weight percentage ( 3 . 0 % w / w ) of refined safflower oil . the other formulation ( r6539 ) was similar in composition to the first formulation , but lacked any safflower oil . in both formulations , the hc17 - b was present in a weight percentage of 0 . 1 . table 1 shows , respectively , the recipes for the two formulations , showing the various components respectively thereof as weight percentages . table 2 shows the analytic results of samples of the resultant respective compositions , showing the exact percentages of the hc 17 - b ( as well as propylparaben and butylparaben ) found in the two formulations expressed as weight percentages . from table 2 , it can be ascertained that the formulation containing the safflower oil had an average weight percentage of 0 . 101 hc17 - b , whereas the sample which did not contain the safflower oil had an average weight percentage of hc17 - b of 0 . 104 , a slightly greater weight percentage . the stability of the respective formulations was tested by analyzing the two formulations over a six - month period , at various intervals . the stability study was performed at a temperature of 40 ° centigrade , considerably greater than normal room temperature . as can be readily ascertained by comparing the six - month results for the two compositions , the composition containing the safflower oil ( r6546 ) did lose some hc17 - b . the weight percentage went from 0 . 101 at the start of the study ( from table 2 ) to 0 . 095 after six months . furthermore , the isomer hc21 - b began to make its appearance at the three - month interval , and was found at the six - month endpoint of the study in a concentration of 5 . 00 weight percent of the hc17 - b content . furthermore , there were various other impurities found at the six - month endpoint in a percentage of 0 . 56 weight percent . in contrast , the formulation which did not contain the safflower oil ( r6539 ), although starting out containing slightly more hc17 - b , it lost this component more rapidly and wound up with a considerably lower weight percentage of 0 . 86 at the six - month endpoint of the study . as would be expected , the formulation without the safflower oil and its constituent linoleic acid contained an even larger percentage of the isomer hc21 - b , namely , 6 . 36 %. furthermore , other impurities were found in this formulation after six months in a much larger percentage as well , namely , 2 . 81 weight percent as compared to only 0 . 56 weight percent . as can be seen from this data , adding the omega - 6 acid component in the form of the linoleic acid - containing safflower oil considerably increased the stability of the valuable hydrocortisone 17 - butyrate compound . in fact , the formulation which did not contain the safflower oil lost approximately 18 % of its original hc17 - b , whereas the formulation containing the safflower oil lost only approximately 6 %. in other words , the improvement in stability was practically threefold . furthermore , the level of the hc21 - b isomer and the other impurities was about 60 % less in the formulation containing the safflower oil than in the formulation where the safflower oil was absent . thus , adding an omega - 6 acid component in the form of safflower oil has been shown to be an effective way of stabilizing 17 - substituted hydrocortisone compounds . while the methods and compositions of the present invention have been described with reference to certain exemplifications and embodiments thereof , the invention is by no means limited to the specifically depicted examples and embodiments . for example , other 17 - substituted hydrocortisone compounds could also be stabilized through the use of the present invention . the omega - 6 acid component could be provided in other forms than as linoleic acid generally , or as safflower oil specifically . it is only necessary that the omega - 6 acid component be provided in a form which is pharmacologically compatible with topical hydrocortisone creams and lotions . doubtless , one of skill in the art could , after routine experimentation , employ other pharmacologically compatible omega - 6 components with similar efficacy without departing from the scope of the present invention . it is the claims appended hereto , rather than the exact exemplifications and embodiments , which define the scope of the present invention .	0
with reference to fig1 , this invention has an ambiguity envelope ( ae ) security system 10 , which has a bounded random number generator function 16 , an ambiguity envelope function 12 and a jitter function 14 . the output of the bounded random number generator function 16 is called bounded random numbers or brns 17 . brns 17 are input to the ambiguity envelope function 12 : the ae function 12 using a shuffling and pairing sub - function 22 , and an envelope creating sub - function 24 creates an ambiguity envelope 13 . an envelope offset sub - function 26 uses envelope 13 and when inputted packet number 22 , outputs an envelope offset 27 , which is input to the jitter function 14 . the jitter function 14 using the input of the ambiguity envelope offset 27 and the prior art key 20 outputs random - variant - keys 18 . the ae implementation uses a small memory and processing throughput footprint that rides over the existing prior encryption schemes thus making the ae implementation relatively convenient in prior art encryption devices and prior art devices that embody embedded encryption mechanisms . integrated circuits , firmware and components that facilitate use of ae may be manufactured and sold to manufacturers of wireless devices such as cell phones , wireless access points , and other devices . with respect to upper part 60 of fig2 , the system 10 uses prior art encryption scheme using encryption algorithm 42 , seed value 44 , plain text 46 and encryption key 20 over a prior art wireless network 40 . as illustrated in lower part 62 of fig2 , in ae 10 , the prior art encryption key 20 is jittered or randomly modified to create random - variant - keys 18 for each packet # x . the random - variant - key 18 is then what is used for each packet instead of the prior art key 20 . the random - variant - key 18 is like the prior art key 20 in every respect including the key length . the difference between the random - variant - keys 18 and the encryption key 20 is that the random - variant - keys 18 are randomly created variants of the encryption key 20 . as shown , the random - variant key 18 is created by a jitter function 14 to which is input , the prior art encryption key 20 , and the ambiguity envelope offset 27 . the offset 27 is output by the ae function 12 , when the ae function 12 is input the packet sequence # x 21 . the envelope 13 , which is used to compute the offset 27 is based on the brns 17 and the ae parameters 48 as described later . in the ae function 12 , the packet sequence # x 21 is used to read an offset value 27 from the envelope 13 and is used by the jitter function 14 to create a random - variant - key for that packet number # x 21 . the ambiguity envelope 13 has x - axis as packet sequence number and y - axis has as the amplitude or offset of the envelope . this offset value is read from the envelope for a given packet number and is used by the jitter function 14 to create a random - variant - keys 18 for this packet . hence , the random - variant - keys are different for every packet and is created at the time of use for one time use in the temporary memory and then discarded . a time slice such as one second or some other time , in place of packet number 22 may also be used . the packet number is preferred as it is a recognized unique prior art mechanism to identify the order and sequence of transmission of packets between the two ends of transmission . however a time slice instead of packet may also be used provided the time system clocks at the ends of transmission are synchronized and can be relied upon . with reference to fig2 , the ae function 12 and jitter function 14 are present at both ends of the transmission path . for illustration purposes , the line 40 divides the transmitting end 40 a and the receiving end 40 b . the brns 17 and the ae parameters 48 enable the random variation of the prior art key 20 resulting in random - variant - keys 18 . the brns 17 are created at one end of the transmission path and then transferred to the other end by an out - of - band method depending upon the application as described later with reference to fig4 , 6 and 7 . with reference to fig1 and 2 , ae parameters 48 determine how the brns 17 are transformed into an ambiguity envelope 13 using shuffling and pairing function 22 and a envelope creation function 24 . the offset function 26 outputs an offset 27 of the envelope 13 when input a packet sequence 21 . these functions 22 , 24 and 26 are described in more detail later and add or provide multiple degrees of random separation from the brns to the envelope itself . thus knowledge of the brns 17 themselves does not provide knowledge or computation of the ambiguity envelope 13 . the ae parameters 48 may be unique and different for different classes of wireless devices that use encryption such as wireless access point &# 39 ; s network and cell phones . with reference to fig1 and 2 , in a system of encryption for communication security that uses an encryption algorithm 42 and a pre - placed encryption key 20 , this invention provides a security function 10 that generates a sequence of random - variant - keys 18 one at a time , on a per packet basis in temporary memory of an encryption device from the pre - placed key 20 at the time of encryption and not before and uses these random - variants - keys 18 for encryption instead of the pre - placed key 20 and immediately thereafter discards the random - variant - keys 18 . prior art random generators of any type may be used to generate a sequence or set of random numbers of specified number of digits . when the random number is limited to a specified number of digits it may be called a bounded random number or a brn . for example , if an up to 2 digit random number is derived from a larger random number generated from a prior art random number generator function it is a bounded random number . the random numbers may be bounded to any number of digits depending upon the application . for some applications they may be single digit bounded and for some other applications they may be bounded to such as 2 or many more digits . further , a sequence of such bounded random numbers is created . such a sequence may have a short sequence of 6 , or a medium sequence , or a long sequence that have many tens of bounded random numbers . a sequence that is even and of at least six numbers is preferred as is described later . these bounded random numbers are used for creating an indeterminate envelope as described later . the envelope is considered indeterminate having multiple stages or degrees of random separation from the brns themselves . this function has three sub - functions as described here . the input to the function 12 is the sequence of brns from the function 16 and the output is an ambiguity envelope offset 27 , which is input to the jitter function 14 . the three sub - functions are : this sub - function takes the brns 17 shuffles them , and then pairs them so that each pair may describe cycle time and amplitude parameters of a wave . as a simplified illustration , if there are six numbers , 12 , 45 , 56 , 23 , 67 , 98 generated in that order by the brn function 16 , then the shuffling function shuffles this sequence in one of many shuffles . an ae parameter 48 a may be used to define one of many shuffle approaches . the shuffled brns are then paired in three pairs . another ae parameter 48 b may be used to define the pairing . the pairs then may be further shuffled to define which of the number of a pair represent the cycle time of the wave and which represents the amplitude . the output of this sub - function is a number of pairs . as a simplified illustration , when the brns are six in number , output of this function , are three pairs of numbers , where each pair represents the cycle time and amplitude of a wave . the three wave pairs from the six brns after the operation of this function may be ( 56 , 98 ), ( 45 , 12 ), and ( 23 , 67 ) where the first number of the pair is cycle time and the second number is the amplitude . in this function , each pair of brns is then mapped to a wave type such as a sine wave , or a square wave or a triangle wave . again an ae parameter 48 c may define which one of many possible approaches to mapping may be used . the wave types are chosen to be a sinusoidal , a triangle and a square wave type . other wave types may also be used but these wave types are preferred as they are defined by a pair of numbers that map to two of the brns and are distinct in their properties of how their amplitude on y - axis varies along the x - axis . once the mapping to the wave types is done , this function then takes the three waves and additively combines them into one envelope . by adding these wave types of different types results is an ambiguity envelope 13 . optionally a phase value may be assigned to each of the waves before they are additively combined if one of the brns may be used to represent a phase value . in addition , a phase may be added to the entire envelope , where such a phase would be different for the sending and receiving ends of the transmission . how the brns 17 may be converted to an ambiguity envelope 13 has been described . many approaches in addition to the above may be used and are not ruled out . the shuffling , pairing and then shuffling within the pair that map to one of the wave types provide different types of random approaches to separate the envelope from the brn itself . mere knowledge of the brns themselves would make impossible the creation of the envelope . alternatively the brns may be straight forward used to create an envelope without the use of shuffling , pairing and shuffling with in pairs as defined by the ae parameters 48 . however , it is believed that these functions add different types of randomness for the creation of the envelope from the brns and thus provide additional level or layer of security . therefore , the compromise of the brns does not affect the security as provided by this invention in creating random - variant - keys 18 . furthermore , the ambiguity envelope 13 that results is indeterminate and could not have been duplicated by any means as it is a summation of different wave types , randomly selected , and used randomly assigned parameters from a random set of parameters . the ambiguity envelope does repeat but at a random cycle time . the cycle time of the envelope is based on the factorial of the cycle time of the three waves . for example , if the three cycle times are 56 , 45 and 23 , then the cycle time of the envelope would be a lowest number that is divisible by 56 , 45 and 23 . hence the ambiguity envelope is indeterminate having been derived from the brns by a series of operations as described herein . the amplitude of the envelope 13 would randomly vary between the positive and negative values of maximum of sum of individual wave amplitudes . hence the offset value 27 for a packer sequence number # x 21 may be positive or negative between these maximums or zero . given the same brns 17 at the two ends of the transmission and the same ae parameters 48 , the same ambiguity envelope can be created . there may be two envelopes at each end of the transmission , one for generating random - variant - keys for encrypting outgoing packets and one for generating random - variant keys for decrypting the incoming packets . these two different envelopes may use a different set of brns or use the same set of brns but add a different phase to the envelope , so that a different random - variant - key would result for the incoming packet and the outgoing packet , even if the packet sequence number is the same and even if the packet sequence number is different . in a real transmission the packet sequence numbers may be different as more packets may be transmitted in one direction than in the other direction . for example when the same brns are used at the two ends , the phase offset may be zero at one end and another number at the other end . for this offset , some of the numbers from the sequence of the brns themselves may be used . this function , when input a value for an x - axis , computes a y - axis value from the ambiguity envelope . the x - axes value is a packet sequence number in a session of communication . the y - axis is an envelope offset which is input to the jitter function 14 . this function is input the packet sequence number at the time of the packet creation and outputs an offset value . the offset value from the envelope for a given packet sequence number maybe an integer , maybe an integer plus a fraction , or maybe positive or negative or zero . this offset may be used in a variety of random ways to provide random - variant - keys 18 as described in the jitter function 14 . the jitter function 14 transforms the y - axis offset of the envelope into a series of numbers and this series of numbers is used to alter the pre - placed key 20 to arrive at a random - variant - key 18 , where each y - axis offset yields a new random - variant - key . the jitter function 14 may use one or a combination of techniques of , ( i ) the pre - placed key is altered by performing an operation such as bit reversal corresponding to the series of numbers , ( ii ) the pre - placed key is altered by performing an operation such as adding or subtracting the offset from the pre - placed key . any number of possible approaches from the envelope offset maybe used to create random - variant - keys in addition to the two described above . as a simplified illustration , using the first technique , if the offset is 329 . 7 , the series of numbers derived from this offset may be 3 , 2 , 9 , 32 , 29 , 39 , 5 , 11 , and 14 by a combination of the numbers 3 , 2 , and 9 . these bit numbers in the key may be flipped from a 0 to 1 or a 1 to a 0 . as a simplified illustration , using the 2 nd technique , the offset number 329 may be added to the prior art key at the 7 th bit position from one end of the key . other similar techniques that are derived from the offset value may be used . these techniques are embedded in the jitter function 14 that is present at both ends of the transmission . the technique that is used in a jitter function may be different for different classes of the devices that use the security function 10 . for example one technique may be used in cell phones and another technique may be used in the wireless access points of a network . a third technique may also be used for creating random - variant keys 18 . this third technique may create two random - variant - keys for each packet that may be used as layers of keys for double encryption . for example , technique 1 may be used to create a random - variant - key 1 18 and technique 2 may be used to create a random - variant - key 2 18 a as shown in fig3 b - 1 and 3b - 2 . then key 1 may be used to encrypt a data packet and key 2 may be used to further encrypt the same data packet . this technique provides an additional level of randomness in the generation of random - variant - keys and an additional layer of security . for a given packet even if brute force approach were attempted to break the random - variant - key for that packet alone , the plain text of the packet &# 39 ; s data contents would not result and would not verify the accuracy of the random - variant - key . fig3 a and 3b - 1 & amp ; 2 describes the operation of the security function 10 . as shown security function 10 of fig1 , has three steps , 82 , 84 and 86 . step 82 is a bounded random number ( brn ) function . the step 84 is an ambiguity envelope function . step 86 or 87 , is a jitter function . step 82 , as in fig3 a is a bounded random number ( brn ) generator function . it is used to create six two - digit numbers . since , such numbers are commonly used in a lottery , the output of step 82 , as such , may be named a lottery number . hence step 82 generates a lottery number made of six two - digit numbers . where manual methods maybe used to copy a brns from one device to another device , the concept of lottery number makes it easier to humanly read , receive and enter into a device . in this description , the terms ae coefficients , lottery number and brn mean the same thing and may be used interchangeably . these are a set of bounded randomly generated numbers by a random number generator function . when they are limited in size such as one digit , 2 digit , etc , they are referred to as bounded random numbers . when they are bounded to 2 digits and are six in number they are referred to as a lottery ticket , as customarily , a lottery ticket has six two - digit numbers . however , depending upon the application the brn may be longer numbers and may correspond to more than six numbers . step 82 is performed on one end of the two points of a wireless transmission path . which end of the transmission link it is performed , how often it is performed or the brns are refreshed and how the brns are carried or conveyed over to the other end of the transmission path is illustrated later with reference to fig4 , 6 and 7 for different applications . thus having the lottery number , ae coefficients or brns at both ends of the transmission now leads us to step 84 . as shown in fig3 a , step 84 has four sub - steps 1 to 4 . optionally an ae flag 33 may be used to turn the features of security function 10 on or off in a given application . in sub - step 1 , the ae function 12 takes the lottery number 17 and creates an ambiguity envelope 13 . a simplified representative envelope 13 is shown . the envelope 13 has an x - axis and y - axis . the x - axis is packet sequence number 21 and y - axis is amplitude or offset 27 for the packet sequence number 21 . three different ae parameters 48 may be used to quantify how the brns 17 may be transformed into an ambiguity envelope . the ae parameters may be , ( i ) wave pairs ( wp ), ( ii ) wave order ( wo ), and ( iii ) wave type ( wt ). as an illustration , if the brn is a set of six two digit numbers 24 , 64 , 23 , 89 , 72 44 , then for example , wp may be 1 , 6 , 2 , 4 , 3 , 5 . this means that 1st and 6th number form a pair , 2 nd and 4 th number form a pair and 3 rd and 5 th number form a pair , so that the pairs that define a wave are ( 24 , 44 ), ( 64 , 89 ), and ( 23 , 72 ). the wo defines in each pair , which number is cycle time and which number is amplitude . for example , wo may be , ( 23 is cycle time and 44 is amplitude ), ( 64 is amplitude and 89 is cycle time ) and ( 23 is amplitude and 72 is cycle time ). the wt defines the type of each of the waves , such as , first pair represents a triangle wave , second pair represents a square wave , and third pair represents a sine wave or even a cosine wave . these ae parameters take the original six randomly generated numbers and turn them into three waves , each with an amplitude and cycle time . thus the lottery number yields three waves of different amplitudes , cycle times and different shapes or types based on the lottery number set of six numbers . then these individual waves are additively combined to yield an ambiguity envelope 13 . these steps of starting from the random bounded random numbers 17 and arriving at the ambiguity envelope 13 provide different types of randomness and break the chain of mathematical causation between the brns 17 and the ambiguity envelope 13 . having a different set of ae parameters 48 enables ae function 12 to be different from application to application or even among applications by assigning a version number to the ae function . the ambiguity envelope would repeat after a number that is equal to factored number of multiplication of three cycle times . for example , if the cycle times of the three waves are 33 , 67 , 99 , and since 99 is divisible by 33 , then the envelope would repeat after 99 × 67 packets or seconds ( if time slice is used ), because at that interval , a whole number of each of the waves are present . the ae function 12 , performs the tasks of , given or initialized with a lottery number , creates the ambiguity envelope as described above , and when is inputted a packet sequence number or time sequence , looks up the corresponding offset for it . the amplitude or offset of the ambiguity envelope may be positive , zero or negative for different packet sequence numbers . it may be a whole number that may be rounded from a fraction or may be fraction . at sub - step 2 , the standard 128 - bit encryption key and the offset from the ambiguity envelope function 12 is input to the jitter function 14 . the jitter function 14 then yields a random - variant - key 18 for a given packet sequence number , as illustrated in step 86 . at sub - step 3 , a standard encryption function 42 is used with the random - variant - key 18 . at sub - step 4 , a function keeps track of the incoming and outgoing packet sequence numbers by incrementing these two variables . these variables are used in sub - step 1 and sub - step 3 as shown . the step 84 functions of ae function 12 and jitter function 14 , as outlined above , are duplicated in the software or firmware at both the ends of the wireless transmission . the separate incoming and outgoing packet sequence numbers synchronize the generation and use of the random - variant - keys 18 at both ends of transmission . generally for each transmission / communication , the packet sequence number is initialized . however , there may be reset or synch commands exchanged between the two ends of transmission that would reset or re - synch the packet counters to either zero or another fixed number . alternatively , instead of packet number a time such as in seconds referenced to the beginning of the session may be used . when time is used the ambiguity envelope on the x - axis will have time in seconds . a particular offset for a given time read on the x - axis may be used until the next time segment . the offset 2 is used to jitter or vary the prior art key 20 . for example , if the ae offset is 69 , this number may be used arbitrarily so that the random - variant - key for this packet may be where the 6 th , 9 th , 15 th and 69th bit are flipped in the 128 bit encryption key . if offset is zero , the packet data may be dummied up . if offset is negative , then a slightly different jitter approach may be used or the negative may be treated as a positive offset . if the offset is a whole number and a fraction such as 79 . 23 , then these numbers may be used to decide which of the bits will be altered or flipped . the random - variant - keys , as described above , have no mathematical relationship to the original static key 20 . thus the jitter function 14 creates a large number of random - variant - keys 18 from one original key 20 that permit a different random - variant - key to be used for each packet as long as the incoming and outgoing packet sequence numbers remain synchronized at the two ends of the wireless transmission path . in an alternative scheme different layers of random - variant - keys may be used . for example , what is described above with reference to fig3 b - 1 may become the first layer of random - variant - keys and what is described in step 87 , in fig3 b - 2 may become the second layer of random - variant - key . fig3 b - 2 illustrates that the offset number itself may be used to create another key , where the offset number is placed in some random variable location of the 128 bit key . as an illustration , if the offset is 329 . 72 , the second layer of random variant key may be the number 329 starting in the 72 nd bit location . similar other schemes may be used based on the offset . now with the help of fig4 to 7 , different applications where the security function 10 of fig1 and 2 may be used are described . fig4 describes a wireless network application , fig5 describes a cell phone application , fig6 describes a mobile ad hoc wireless network application , and fig7 describes the use of optical means for distribution of brns in some of the applications . with reference to fig4 a , this invention describes a system of security 100 in a nationwide wireless network that uses the security function 10 of this invention . the system 100 may use adapted wireless access points ( waps ) 140 connected to either a local area network , a wide area network of a business or to a global network 112 . the waps may be used by wireless devices such as laptops 132 , of users with cell phones 130 . the users may be employees of a business , or at large users who have subscribed to this service as described herein . in the system 100 , there is a call screening function 102 that receives cellular calls with caller id and geographic cell data and screens permitted calls based on a pre - stored list of caller id ; a call mapping function 104 that maps the call to a wap in the area identified by the cell ; and a call routing function 106 that routes the call to a telephone number assigned to a wap in the area . the service related to functions 102 , 104 , and 106 maybe provided by a service provider or the service maybe provided by a cellular telephone company 120 , which provides the telephone numbers . it is to be noted that the cell network provides a unique caller id mechanism that is tied to the sim card of the cell phone , along with a cell based geographic location identification of the caller &# 39 ; s physical location at the time the call was made . some of these functions , 102 , 104 and 106 may be provided by a cellular company and other functions provided by a service provider . for example , the cellular company may provide caller id and geographic location data for each call and the cellular company 120 may maintain a list of authorized account holder caller ids , who have subscribed to this service and screen calls against this list and forward such screened calls to a service provider . the service provider may a business entity that maintains the servers that facilitate the automatic operation of functions 102 , 104 and 106 . the service provider then may map the caller id and location data to a wap in that geographic area . the mapping may be based on both the geographic area as well as the caller id . this dual mapping would enable identifying and mapping the callers to those waps that are available for certain network as those belonging to a national business based on caller id identification . this would enable different wap and networks to be maintained for different national companies . the service provider then is able to route the calls from cell phones to a specific wap in the geographic area . in this system of security 100 , the prior art wap 108 is adapted with a telephone interface and a simplified ivr 110 that is able to voice deliver a sequence of numbers resembling a lottery ticket , such as two digit brns , to the caller . the wap 108 is further adapted with the functions of security function 10 , as was described earlier with reference to fig1 . these functions are bounded random number generator function 16 , ambiguity envelope function 12 , and jitter function 14 . these functions ( i ) generate brns , ( ii ) converts the brns numbers to an envelope , with x - axis packet and y - axis identifying envelope amplitude as an offset , and ( iii ) using the offset as a parameter provide random variants of the pre - placed encryption key and using the random - variant - key as the encryption key in place of the pre - placed key for encryption in the wap . the adaptation of wap 108 also includes a function to receive a call , create a data record anchored by the caller id of the call , and select a port number that may be assigned to this caller , use function 16 to generate brns 17 . the adapted wap 140 maintains data records with the information fields of , time stamp of the call , caller id of the call , port number assigned to this call and the brns that were generated for this call . similar records are maintained for each call that is received by the adapted wap 140 . the wap 140 may also have a feature to delete such a record at the end of session or 24 hours which ever occurs first the wireless card 134 present in the laptop computer 132 of the user is an adapted wireless network interface card . the wireless interface card 134 adapted with a function to display and be able to input a series of random numbers and a port number of a wap via a display screen 122 . the wireless card is further adapted with some of the function of security function 10 that is the ambiguity envelope function 12 and jitter function 14 . these functions ( i ) converts the brns numbers that are received via screen 122 , to an envelope , with x - ax - packet and y - axis identifying envelope amplitude as an offset , and ( ii ) a function that using the offset as a parameter provide randomly variants of the pre - placed encryption key and using the random - variant - key in place of the pre - placed key for encryption in the wireless card 134 . the wireless interface card 134 of the computer device 132 is adapted to work with the adapted wireless access point 140 . hence , the adapted wap 140 and the adapted wireless card 134 are able to use random - variant - keys for encryption and decryption of the wireless communication between the wireless card 134 and the wap 140 . fig4 b illustrates the operation of the nationwide wireless application of this invention . at step 1 , the laptop computer user equipped with an adapted wireless card , using his cell phone , calls a designated telephone number . at step 2 , the cell phone company 120 receives the call . at step 2a , the service provider performs a screen function , which screens the call as one who has subscribed to the service , based on caller id and then routes the call to a map function . at step 2b , the map function maps the call &# 39 ; s geographic cell location to available waps in that cell location . the mapping in addition to the physically proximity of the wap to the cell location may also use the caller id for mapping . the caller id mapping may be able to differentiate those waps that belong to a private business network belonging to a national business and are allowed to be used by pre - identified callers with pre - registered caller ids with this business . if the mapping function is unable to map such a refinement of location , due to multiple waps in the same location , the caller may be asked to select from a sorted list of locations in the specific cell by the map functions . at step 3 , the cellular company uses a route function , which routes the call via a public telephone network 121 to the specific wap approved for the caller &# 39 ; s use from the collection of waps in the database . at step 4 , thus the call , after being routed through the screen function , the map function and the route function , is answered by the specific wap adapted with a telephone modem interface with an ivr . the caller is unaware of these functions and the call is answered by the specific wap close to the caller &# 39 ; s physical location . at step 5a , the wap 140 creates a record with the time stamp and caller id , assigns a port number , generates and stores in the record the brns , and voice delivers brns to the caller along with the port number . at step 5b , the wap 140 monitors the sessions and deletes the record , if the wireless communication session is not established within a specified time threshold of the time of delivering the brns to the caller and deletes the record at the end of the session or up to a time limit such as 24 hours if the session is continuing . thus the wap does not maintain a long list of records anchored by the caller id and the port number and frees up the port for other users . at step 6a , the caller hears the seven numbers port number and the six brns and at step 6b enters them into the screen 122 that is provided by the adapted wireless card . the caller enters his caller id and clicks ok to complete step 6b . in this application , the caller id of the phone that is used to call the wap or some other number that is created by the caller may be used for authentication between the laptop and the wireless access point . if the caller id is used it is automatically recorded from the call by the wap , and is also entered by the user along with lottery numbers in screen 122 as shown in fig4 b . this number may be used in the body of the data packets to authenticate the laptop to the wap and vice versa . at step 7a , the adapted wireless card stores the brns and uses security function 10 to create random - variant - keys that are used in place of the standard key for encryption and decryption of the wireless communication . at step 7b , a similar function is performed in the wireless access point 140 . at step 8 , the packets that are exchanged between the laptop and the wap may provide the port number in the header of the packet in addition to the prior art information such as ssid . this enables the wap to identify the packets for one of the ports and be able to find the record that has the caller id and the brns and know which brns to use for this particular laptop transmission for this particular user . this enables the wap to apply the right envelope and the right random - variant - keys to decrypt the packet and find in the data the caller id , which is used to authenticate the laptop user as the one who made the call and was given this set of brns . cell phones and similar wireless devices are used by individuals , law enforcement groups , business entities , and other special groups who may wish to add extra security to their conversations and data transmittals than what is provided by the digital phones themselves as part of wireless security by the cellular telephone companies . such wireless devices are used for both voice and data communication . as part of the encryption already provided in digital cell phones , an encryption key that may be part of the sim of a cell phone encrypts the wireless communication from the cell phone to the cell company network , where the cell company decrypts the communication and may route it on a land line to the network of the recipient cell phone company , where the recipient phone company encrypts it with the encryption key of the recipient phone and routes it wirelessly to the recipient phone . thus this encryption security as provided by prior art devices protects the wireless part of the communication . many people are of the opinion that this encryption is not strong and may be broken by determined parties . the security provided by the security function 10 as described earlier with reference to fig1 may additionally be provided to such a wireless or cellular network . the security function 10 may be adapted in the cell phones to work at a layer below the mode of encryption security in prior art cell phones , thus leaving the prior art encryption intact . with reference to fig5 , a system of security 200 against eavesdropping between handheld wireless devices such as cell phone communication based on security function 10 is described . the system 200 has prior art cell towers 220 , prior art cell phones 202 , and prior art caller id 204 associated with each phone . in system 200 , each cell phone 202 is adapted to provide the security function 10 as has been described earlier with reference to fig1 . in this adaptation , each cell phone is further adapted with an ae cell phone function 206 , brn function key 208 and ae function key 210 . the ae cell phone function 206 provides interfaces to soft key 208 and soft key 210 and maintains a table 212 . the table 212 maintains a list of phones identified by caller id 204 and their corresponding brns 17 . when the brn function key 208 is activated , it launches the brn function 16 of the security function 10 and displays brns 17 on the screen of the phone 202 . these brns 17 are then manually transferred or copied to other cell phones . the brns may also be transferred via an optical interface , if the phones 202 are equipped with such an interface . the function 206 maintains a table 212 , which for each caller id 204 maintains the corresponding brn 17 . thus function 206 allows each phone to maintain a brn for itself and each phone it may choose to communicate with the use of security function 10 . soft key 210 enables each phone 202 to choose to activate the security function 10 for all calls or for some calls by turning the soft key on and off . when the soft key 210 is off , the phone works like a prior art phone without using the security function 10 . hence , in this system 200 , each phone may selectively enable and disable the security function 10 for each communication by setting a flag via soft key 210 that is under the control of the user . in fig5 , for the purpose of explanation , one of the cell phones 202 is identified as cell phone a 202 a and another is identified as cell phone b 202 b . when cell phone a communicates with the cell phone b , and when the soft key 210 is activated in the cell phone a , the cell phone a activates the function 206 . the ae cell phone function 206 searches for the brns in the table 212 , that are applicable to the caller id 310 332 4343 of cell phone a ( caller phone ), as 345679 and searches for the brns in the same table 212 , that are applicable to the caller id 626 332 4834 of cell phone b ( called phone ). the function 206 with the help of function 10 uses these brns to generate random - variant - keys and uses random - variant - keys for encrypting outgoing transmission that are from the brn associated with own caller id and uses the random - variant keys for decryption that are from the brn that is associated with the caller id of the other phone in the table 212 . a similar operation takes place in the called cell phone b . cell phone a and b each equipped with a security function 10 that generates brns for each phone or caller id , converts each brns at each end into an ambiguity envelope , with an x - axis and a y - axis and with a jitter function 14 that using the offset from the envelope creates a time and packet dependent sequence of random - variant - keys from the existing key and use such keys for encryption . hence in this application , it is possible , while leaving all the functions of existing cell phone intact , add or overlay ae encryption security between any two or more specific cell phones . each cell phone pair may have software functions that enable a layer of encryption using ae in addition to what ever is used in prior art . hence , the ae can be optionally be used between any two phones and not other phones and not all phones and it may be activated or deactivated to be used or not used for each call . when the call is received at a cell phone and if ae is on , then it checks the caller id against the list and if a brn is found , which will be the same as used by the caller , then ae encryption is used . the system of security 200 has an exchange mechanism where the cell phones may use manual , infrared , and radio frequency means of exchanging the brns . ae may also be used in many other wireless as well as wired applications that are not described here . some times ad hoc wireless networks may need to be set up in remote areas and or in a theatre of operation . fig6 shows the mobile ad hoc wireless network application 400 most likely to be used in a theatre of operation . assuming such an application 400 has a base station 402 and multiple forward base stations such as 404 and 406 , and each base station supports multiple hand held units 406 and 408 . these base stations 402 , forward stations 404 and 406 and handhelds 406 and 408 may be equipped with the security function 10 as has been described earlier with reference to fig1 . in such an application 400 , brns may be generated in the forward base station 404 and either may be manually keyed in each of the hand sets 406 for this forward base station . alternatively , as shown in fig7 , if the forward base station and the hand held units are equipped with infrared capability , then the brn may be transferred to all hand units at one time within a few seconds from the forward base station by placing them in close proximity to each other . as shown in fig7 , the base station # 2 406 is equipped with an optical transmitting means 410 and each of the handhelds 408 are equipped with an optical receiving means 412 . multiple handhelds 408 may be placed as a group in the optical transmitting path of optical interface 410 and thus would be able to simultaneously transfer the brns to the handhelds 408 . the brns may be changed for each mission or whenever desired for security reasons of the environment where the mobile ad hoc wireless network is put in place . hence , optical means such as use of infrared , if the devices are equipped with infrared sensors such as commonly used in televisions and like , may be used to quickly and efficiently transfer the brns to the other end of the transmission path . different brns may be used for different forward base stations . for example forward base station # 1 404 may use brn 1 that it generated for its hand held units 406 . forward base station # 2 406 may use brn 2 that is generated for its hand units 408 . forward base station # 1 to communicate with forward base station # 2 may generate brn 3 and that may be manually entered in forward base station # 2 or copied via other means . each of the forward base stations may use a different brn such as brn 4 and brn 5 when communicating with the base station 402 . these brns 4 and 5 may be generated by base station 402 and manually communicated and entered in by the people setting up the base units at the time of set up . this having different brns spread out over a theatre of operation of ad hoc mobile network provides additional transmission security . there are many other applications where the security function 10 may be used in addition to the three applications of wireless networks , cell phone networks and ad hoc wireless networks as described above . in an application , the wireless and wired part of a network may be combined to provide the security function 10 over an entire network from end to end . in this application the user of a laptop may directly contact the host computer and receive brns . while the user may still use a wireless network , the security function 10 may provide security over the entire network from the laptop to the host computer including the wireless and the wired part of the network to the host computer . the system of security 10 may also be used in the wireless device that may be bluetooth equipped device , where the communication is between the cell phone and a bluetooth extension of the device such as an earpiece . if the other end of the bluetooth device is an earpiece , which may use prior art means of switches and display window to manually transfer the brn . the cell phone owner reads the brns on the phone and one by one manually transfers them to the earpiece via the switches and the display . this manual operation is required to be done only once by the user or when ever he / she wants to reset the encryption , every few months or year or so . alternatively , if the bluetooth devices are so equipped , the brns may be transferred via bluetooth format or an optical format . another application may be satellite to ground communication , where the brns may be long and complex and are installed in the satellite at launch times or they may be updated at other times by other means . the security function 10 may be implemented in software , firmware and hardware integrated circuits depending upon the application . if implemented in an integrated circuit chip that embeds the security function 10 then it has , ( i ) an interface for inputting a series of bounded random numbers , ( ii ) a logic that converts the numbers to an envelope , with x - axis corresponding to a packet sequence and y - axis corresponding to an envelope amplitude offset for a packet sequence , and ( c ) a logic that uses the offset for a packet sequence number and a static encryption key as inputs and randomly variates the static encryption key outputting random - variant - keys , thereby enabling the use of the random - variant - keys for encryption and decryption of data packets in place of the static key . the use of security function 10 in these and other applications provides for a robust and in - depth transmission security , where the security of the communication is not dependent upon the security of prior art encryption keys and thus reduces the cost and effort of frequently updating the prior art encryption keys and maintaining a key management infrastructure for them . while the particular system and method as illustrated herein and disclosed in detail is fully capable of obtaining the objective and providing the advantages herein before stated , it is to be understood that it is merely illustrative of the presently preferred embodiments of the invention and that no limitations are intended to the details of construction or design herein shown other than as described in the appended claims .	7
fig1 a , 2 and 2 a display one possible embodiment of the present invention . the figures display a template 11 manufactured , for example , using stereo lithography ( sla ) from a suitable material such as an extra clear resin . the template 11 has a body 13 that generally corresponds to the shape of the object targeted for gross error evaluation . the shape of the body 13 could be determined from a solid model computer file of the object targeted for gross error evaluation . the body 13 has an interior surface 15 that faces the object and an exterior surface 17 that faces away from the object . the interior surface 15 includes a plurality of protuberances 19 . the protuberances 19 contact the object , and keep the remainder of the body 13 offset from the surface of the object . the protuberances 19 preferably have a height that accommodates variation in object size without the remainder of the body 13 contacting the object . the location of the protuberances 19 could conform to a point system used during the manufacturing process . preferably , the body 13 has six protuberances 19 since the point system used during the manufacturing process identifies six points on the object . fig1 a is a detailed view of the exterior surface 17 of the body 13 . the exterior surface 17 preferably has one or more scribe lines 21 thereon . if formed during an sla process , the scribe lines 21 could be grooves that extend a distance into the exterior surface 17 of the body 13 . the present invention could utilize other suitable techniques to form the scribe lines 21 . for example , the scribe lines 21 could be printed indicia . in other words , the scribe lines are printed onto the exterior surface 17 of the body 13 . the scribe lines 21 allow the user to evaluate the object , specifically a feature of the object , for gross errors . accordingly , the scribes lines 21 are positioned on the exterior surface 17 so as to correspond to the location of such feature on the object . as shown in fig1 a , the template could have two scribe lines 21 per feature . one scribe line 21 could identify a minimum of a tolerance range for the location of the feature on the object . the other scribe line 21 could identify a maximum of a tolerance range for the location of the feature on the object . the template 11 could also include printed indicia 23 to identify the object targeted for gross error evaluation . for example , the printed indicia 23 could be the part number of the object targeted for gross error evaluation . other manners of identifying the object targeted for gross error evaluation , however , could be used . fig2 and 2 a display one possible application of the template 11 . the object targeted for gross error evaluation in the figure is a blade 50 of a gas turbine engine ( not shown ). the blade 50 includes a root section 51 for securing to a disc , an airfoil section 53 for converting the velocity of the fluid exiting the combustion section ( not shown ) of the engine into rotation of the disc , and a medial section 55 between the root section 51 and airfoil section 53 . the manufacturing process for the blade 50 identifies points 57 thereon . preferably , the manufacturing process identifies six points 57 on the blade 50 . due to the exposure of the airfoil section 53 to the high temperature fluid exiting the combustion section of the engine , the airfoil section 53 can have apertures 59 in communication with a hollow interior ( not shown ). cooling air ( not shown ) provided to the hollow interior exits the apertures 59 to provide film cooling to the blade 50 . the template 11 allows the user to ensure , after the manufacture of the blade 50 , that : ( 1 ) the apertures 59 exist on the suction side of the airfoil section 53 of the blade 50 ; and / or ( 2 ) the apertures 59 are properly located ( i . e . within the tolerance range of the location of the feature on the object ) on the suction side of the airfoil section 53 of the blade 50 . as seen in fig2 , the blade 50 receives the template 11 . the protuberances 19 engage the blade 50 at the points 57 identified during the manufacturing process . once associated with the blade 50 , the user can view through the template 11 to evaluate the blade 50 . fig2 a displays a view through the template 11 with a properly located cooling hole 59 ( the cooling hole 59 has been shown in phantom line to avoid confusion as the cooling hole 59 resides behind the clear template 11 ). as discussed above , the protuberances 19 keep the remainder of the body 13 of the template 11 away from the surface of the blade 50 . the distance between the body 13 and the blade 50 is kept to a minimum to avoid parallax error . fig3 displays another possible embodiment of the present invention . the figure displays a template 111 . the template 111 is preferably used to evaluate a different section of the object targeted for gross error evaluation . save for a change in the hundreds digit , the reference characters identifying features of template 111 correspond to the reference characters identifying the same features of template 111 . briefly , template 111 has a body 113 manufactured , for example , using stereo lithography ( sla ) from a suitable material such as an extra clear resin . the body 113 generally corresponds to the shape of the object targeted for gross error evaluation . the body 113 has an interior surface 115 that faces the object and an exterior surface 117 that faces away from the object . the interior surface 15 includes a plurality of protuberances 119 . the protuberances 119 contact the object , and keep the remainder of the body 113 offset from the surface of the object . the protuberances 119 conform to a point system used during the manufacturing process . preferably , the template 111 has six protuberances 119 . the exterior surface 117 of the body 113 preferably has one or more scribe lines 121 thereon . if formed during an sla process , the scribe lines 121 could be grooves that extend a distance into the exterior surface 117 of the body 113 . the present invention could utilize other suitable techniques to form the scribe lines 121 . for example , the scribe lines 121 could be printed indicia . in other words , the scribe lines are printed onto the exterior surface 117 of the body 113 . the scribe lines 121 allow the user to evaluate the object , specifically a feature of the object , for gross errors . accordingly , the scribe lines 121 are positioned on the exterior surface 117 so as to correspond to the location of such feature on the object . preferably , the template 111 has two scribe lines 121 per feature . one scribe line 121 could identify a minimum of a tolerance range for the location of the feature on the object . the other scribe line 121 could identify a maximum of a tolerance range for the location of the feature on the object . the template 111 could also include printed indicia 123 to identify the object targeted for gross error evaluation . for example , the printed indicia 123 could be the part number of the object targeted for gross error evaluation . other manners of identifying the object targeted for gross error evaluation , however , could be used . fig4 displays the template 111 mounted on the blade 50 . the template 111 allows the user to ensure , after the manufacture of the blade 50 , that : ( 1 ) the apertures 59 exist on the pressure side of the airfoil section 53 of the blade 50 ; and / or ( 2 ) the apertures 59 are properly located ( i . e . within the tolerance range of the location of the feature on the object ) on the pressure side of the airfoil section 53 of the blade 50 . the protuberances 119 engage the blade 50 at the points 57 identified during the manufacturing process . comparing fig2 and 4 ( note the figures show different sides of the blade ), it is clear that the protuberances 119 contact the same points on the blade 50 as the protuberances 19 when using the template 11 . fig5 - 7 display another possible embodiment of the present invention . the figures display a template 211 . the template 211 is preferably used to evaluate a different section of the object targeted for gross error evaluation than templates 11 , 111 . the template 211 has features corresponding to the features of templates 11 , 111 . these features used the same reference character , save a change in the hundreds digit . template 201 does have features different that those described with templates 11 , 111 . the features will have different reference characters . briefly , template 211 has a body 213 manufactured , for example , using stereo lithography ( sla ) from a suitable material such as an extra clear resin . the body 213 generally corresponds to the shape of the object targeted for gross error evaluation . the body 213 has an interior surface 215 that faces the object and an exterior surface 217 that faces away from the object . the interior surface 215 includes a plurality of protuberances 219 . the protuberances 219 conform to a point system used during the manufacturing process . the template 211 could also include printed indicia 223 to identify the object targeted for gross error evaluation . for example , the printed indicia 223 could be the part number of the object targeted for gross error evaluation . other manners of identifying the object targeted for gross error evaluation , however , could be used . due to the location of the feature on the object , the template 211 also includes a section 225 having a depressed area 227 . the depressed area 227 has scallops 229 therein . the scallops 229 allow the user to evaluate the object , specifically features of the object , for gross errors . accordingly , the scallops 229 are positioned on the depressed area 227 of the section 225 so as to correspond to the location of such features on the object . fig8 displays the template 211 mounted on the blade 50 . the template 211 allows the user to ensure , after the manufacture of the blade 50 , that : ( 1 ) the apertures 59 exist on the radial tip of the airfoil section 53 of the blade 50 ; and / or ( 2 ) the apertures 59 are properly located ( i . e . within the tolerance range of the location of the feature on the object ) on the radial tip of the airfoil section 53 of the blade 50 . fig8 a shows the protuberances 119 engage the blade 50 at the points 57 identified during the manufacturing process . comparing fig2 and 4 ( note the figures show different sides of the blade ), it is clear that the protuberances 119 contact the same points on the blade 50 as the protuberances 19 when using the template 11 . fig8 a displays a view through the template 211 with a properly located cooling hole 59 ( the cooling hole 59 has been shown in phantom line to avoid confusion as the cooling hole 59 resides behind the clear template 211 ). preferably , the template 211 has five protuberances 219 . the depressed area 227 serves as the sixth contact point with the blade 50 . in the embodiment shown in fig5 - 7 , the location where depressed area 227 contacts blade 50 does not correspond to the sixth point location used with templates 11 , 111 . nevertheless , the protuberances 219 and the depressed area 227 contact the object , and keep the remainder of the body 213 offset from the surface of the object . the present invention has been described in connection with the preferred embodiments of the various figures . it is to be understood that other similar embodiments may be used or modifications and additions may be made to the described embodiment for performing the same function of the present invention without deviating therefrom . therefore , the present invention should not be limited to any single embodiment , but rather construed in breadth and scope in accordance with the recitation of the appended claims .	1
in fig1 two similar profiles 1 to be connected at an angle of 90 degrees in relation to each other are shown . these profiles are provided with a cut away 2 on the extremities facing each other which forms an angle of 45 degrees in relation to the longitudinal direction of the profile 1 . each profile according to the invention consists of a closed cavity 3 , on the one hand , and above this closed cavity 3 an open cavity 4 , on the other hand . the closed cavity 3 shows a lower wall 5 ; two side walls 6 , 7 and an upper wall 8 whereby this upper wall also forms lower wall of the open space 4 which is further completed by side walls , respectively 9 and 10 which as it were form an extension of the aforementioned walls 6 and 7 and flanges 11 and 12 which are provided with the walls 9 and 10 on the free extremities and which are directed towards each other and parallel with the aforementioned wall 8 . in the wall 5 , over the whole length , small holes 13 are provided . the wall 5 extends out on the sides of the walls 6 and 7 and there forms ribs 14 , 15 . furthermore the walls 6 - 9 and 7 - 10 are each provided on their outer side with a quantity of bitumen or similar 16 - 17 which is provided with a covering strip 18 - 19 , of which it is later the intention among others , after removing the strips 18 and 19 , to make a sealing contact with the sheets of glass not shown in the drawings . the connection of the profiles 1 according to the invention is obtained by means of a corner profile 20 that consists of arms , respectively 21 , 22 which in this case are placed at an angle of 90 degrees and that , have a sealing wall 23 in the corner where these arms 21 and 22 come together which is placed at an angle of 45 degrees in relation to the aforementioned arms . in this embodiment the arms 21 and 22 are produced conically in order to simplify their insertion into the profile 1 whereby these arms , at the position where they meet each other , show a thickness which is equal or almost equal to the corresponding measurement of the open cavity 4 of the profile 1 in which the arms 21 and 22 are installed . these thickened places are indicated by 24 , 25 in the drawings . the aforementioned sealing wall 23 in this case is so achieved that it shows two relatively thin parts , respectively 26 and 27 , on its terminal edges which will act as stop for the cut off extremities 2 of the profiles 1 , while the body 28 of the sealing wall 23 is produced thicker and , after installation of the profile 1 over the arms of the corner profile 20 , fits into the closed cavity 3 of the profiles 1 . in order to connect two such profiles to each other it is sufficient to place them to over the arms 21 and 22 of a corner profile 20 whereby these profiles 1 , when they lie with their walls 5 and 8 against the sealing wall 23 , more especially against the parts 26 and 27 of these , preferably fit tightly into the open cavities 4 at the location of the thickened places 24 and 25 of the corner profile 20 . through the open character of the cavity 4 it is achieved that during this insertion of the arms 21 and 22 the flanges 11 and 12 of the cavity 4 can yield somewhat if this should appear necessary . when the profiles 1 are thus secured in relation to each other , as shown in fig2 a distance a will obviously remain in existence between the cut off edges 2 of these profiles which is equal to the thickness of the parts 26 and 27 . since the width of the corner element 20 is equal to the internal distance between the walls 9 and 10 of the cavity 4 ; the thickened parts 24 and 25 of the corner profile 20 are equal to the internal distance between the wall 8 and the flanges 11 , 12 ; the parts 26 and 27 of the corner element 20 are placed between the adjacent walls 8 , on the one hand , and 5 , on the other hand , and finally the thickened part 28 of the sealing wall 23 is placed in the adjacent extremities of the closed cavity 3 of the profiles 1 , in this manner not only an efficient connection is obtained between two profiles 1 , but at the same time an efficient sealing of the extremities of these profiles 1 . when such joined together profiles 1 are subsequently warmed , at least at the location of the corner connection , the material 16 , 17 will melt somewhat and thus fill the space a between the profiles 1 through which an additional seal is obtained . notwithstanding a very good seal is already achieved in the manner described above such a seal can of course still be improved by at least providing the sealing wall 23 and possibly at least a part of the arms 21 and 22 of the corner profile 20 with a covering which can be formed by a soft metal , such as tin , lead or similar , a glue , a plastic , bitumen , or similar , through which not only an additional seal is obtained during the insertion of the arms 21 and 22 in the open cavities 4 of two profiles 1 , but whereby this seal becomes maximally efficient when at the same time at least at the location of the corner connection , heat is applied to allow the aforementioned covering to fill all possible remaining spaces . it is clear that in this case the drying agent that in the known manner is confined in the closed cavities 3 remains completely dry since , for one thing , a good seal is formed on the corners of the frame obtained , this of course on condition that the customary temporary strip 29 which is provided over the holes 13 has not yet been removed . it is clear that it is not necessary that the arms 21 and 22 of the corner profile 20 are produced conically . neither is it necessary that the sealing wall 23 shows a thickening 28 . indeed this sealing wall 23 , as is schematically shown in fig1 by means of dotted line 30 , could show the same thickness over the whole length . through the fact that the arms 21 and 22 of the corner profile 20 are not located in the closed cavities 3 of the profiles 1 it is clear that the frame that is produced in this manner can contain more drying agent than is the case when , as usual up until now , the arms of the corner profile are located in these cavities 3 . likewise it is achieved by placing the arms 21 , 22 of the corner profile 20 outside the cavities 3 and providing a sealing wall 23 , that the outer corner formed by the connection of the walls 8 with the part 26 of the sealing wall 23 as it were becomes an inner corner through which the seal is also improved . in order to make the mutual adjustment of the corner profile 20 even more adjustable in the open cavities 4 weakenings may possibly be provided in the inner corners 31 and 32 between the walls 9 - 10 and the flanges 11 - 12 through which these lips 11 and 12 become more transformable , respectively adjustable . a corner profile 20 according to the invention also further allows that it is easily transformable through which the arms of this can be placed at almost any angle when frames would have to be formed of which the angles are different from 90 degrees . through the design of the profile 1 it is also further obtained that the groove formed between the flanges 11 and 12 of it , which allows access to the open profile 4 can be applied to connect such frames with an additional construction , either by sliding in fixing elements in such cavity 4 beforehand , or by installing already known fixing elements which can block after rotation in such cavity 4 . in a particular application according to the invention implemented frames can be applied in glass walls and similar . finally the corner profile 20 , and / or the profiles 1 , can be implemented in metal , for example aluminum , or in a suitable plastic , whereby in this last case , in order to limit the permeability in the open cavity 4 , preferably an impermeable covering is provided against the wall 8 . it is clear that the present invention is in no way restricted to the embodiment described as example and shown in the drawings , but may be developed in all kinds of forms and dimensions .	8
with reference now to the drawings , and in particular to fig1 through 5 thereof , a new miniature kick bag game and apparatus kit embodying the principles and concepts of the present invention and generally designated by the reference numeral 100 will be described . more specifically , it will be noted that the miniature kick bag game and apparatus kit 100 comprises a court boundary marker 10 displaying a rectangular playing court , portable reticulated nets 16 and 18 formed in an elongated rectangular shape positioned at the center of the rectangular court and aligned vertically thereby dividing the playing court into two team zones , and a foot bag 12 which is kicked by a player 14 with his side of foot 14 over the portable reticulated nets 16 and 18 . as best illustrated in fig1 through 4 , it can be shown that a first support pole 26 engages one end of one of the portable reticulated net supports 20 via an elbow 22 . the opposing end of the first support pole 26 engages a t - support 24 . t - support 24 is adapted to provide linear directional support and guidance to boundary marker 10 . also shown in fig2 , is portable reticulated net 16 suitable attached to net support 20 . it will be appreciated that portable reticulated net 16 may be any suitable material suitable for advertisement marking as shown in fig1 . also shown in fig1 , is second support pole 26 a engaging one end of one of the portable reticulated net supports 30 via an elbow 22 a . the opposing end of the first support pole 26 a engages a second t - support 24 a . second t - support 24 a is adapted to provide linear directional support and guidance to boundary marker 10 . also shown in fig1 , is portable reticulated net 18 suitable attached to net support 30 . it will be appreciated that portable reticulated net 18 may be any suitable netting material . it will be understood that in alternate embodiments net 16 , or net 18 , may be of sufficient length to reach from the first support pole 26 to the second support pole 26 a . referring also to fig3 there is shown is a perspective view of the portable reticulated nets supported by the third support structure . the third support pole 34 engages one end of net support 30 via third t - support 32 . the other third t - support 32 connects net support 20 to the third support pole 34 . the third support pole is also connected to a fourth t - support 36 to provide lateral stability . it will be understood and appreciated that the assembled height of net support 20 and net support 30 when assembled with the first support pole 26 , the second support pole 26 a and the third support pole 34 is approximately 2 feet high . referring also to fig4 there is shown a perspective view of a staked line boundary marker in accordance with the invention shown in fig1 . boundary marker 10 may be any suitable marker such as rope or line . boundary marker 10 may be a predetermined length to form a desired perimeter or measured according to the inventive features described herein . fig4 also shows stakes 10 a for staking boundary marker 10 and thereby defining a corner of the playing area . stakes 10 a may be any suitable stake such as , but not limited to , plastic camping type stakes . referring also to fig5 , there is shown an upper perspective view of the new miniature kick bag game and apparatus kit displaying the built in boundary measuring feature of the invention . net support 20 and net support 30 are predetermined lengths and correspond to the desired dimensions of the court boundaries as shown in fig5 . it will be appreciated that this feature is useful when marking the boundaries on a hard surface that does not permit the boundary marker 10 to be staked with stakes 10 a . it will be understood that any suitable combination of net support 20 and net support 30 may be used to measure and mark the desired dimensions of the court boundaries . for example the combined length of net support 20 and net support 30 could be , in one embodiment , ten feet . the corresponding court size measured by the combined lengths is on one side of the net a ten by ten foot area . the other side of the net is also a ten by ten foot area . basic rules of the game — to start the game you must volley for serve . it does not matter who starts the volley , which can be decided by a coin toss or the winner of the last game . during the volley the hackey sack must be kicked over the net three consecutive times . after the third consecutive times the first team who lets the hackey sack touch the ground loses the volley and looses the first serve , at the volley winner &# 39 ; s discretion . the hackey sack is served , i . e ., kicked over the net support 20 or net support 30 from outside boundary marker 10 . if the hackey sack is kicked out of bounds the serving side loses the serve to the opposing team or player . if the hackey sack is kicked within bounds the opposing team or player may return the serve , without letting the hackey sack touch the ground , with any part of the body except for using their hands . each side has up to three hits or kicks to return the hackey sack . in the case of team play , one person may use all three kicks or hits , or the hits or kicks , up to three , may be allocated amongst the team . points are awarded to the serving player or team when the opposing team lets the hackey sack touch the ground or fails to return the hackey sack within three kicks or hits , or kicks the hackey sack out - of - bounds . a game is won when a team reaches a score of twenty - one points first and is also at least two points over the opposing player or team score ; or , alternatively if a player or team reaches fifteen points before the opposing team or player scores any point . it will be appreciated that the game rules described herein may be suitably modified according to players abilities or preferences . it should be understood that the foregoing description is only illustrative of the invention . thus , various alternatives and modifications can be devised by those skilled in the art without departing from the invention . accordingly , the present invention is intended to embrace all such alternatives , modifications and variances that fall within the scope of the appended claims .	0

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