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The Southern region of Malaysian Marine Department is using the drone technology now to record the videos and images of the oil spill in the waters of Tanjung Balau. These videos and images will help them in identifying the affected areas and implement the cleaning works.
The director of this Marine Department in Southern Region of Malaysia has stated that the use of these drones has helped the person to estimate the extent of the area that is affected by this oil-to-sea discharge.
He has also said that is a common practice for them to use the drones for monitoring any kind of spills in the sea. It is very tough to identify the oil spills in water usually hence the marine department has deployed these drones to make the identification process easier.
These drones will provide a clear aerial view of the oil spill, and to the place, it is headed. They will know where the oil spill will be, either at the beach or in the sea.
This will help the personnel in making their next move, and this includes coming up with a plan to clean up the oil spill. Dickson has also added that these drones will be supervised by the emergency unit of the marine department. The emergency unit will be following the boats and not only assists in the cleanup of oil spills but also comes in handy for any shipwreck event.
He further added that he has the expertise to handle these drones that can be used to record videos and pictures. The drones will keep on recording every movement of the ships. The drones are used in three circumstances- shipwreck, operations to lift the sunken ships and oil spill operations. The drones are also used for maintenance of the navigation tools, etc. | https://www.dronenewshub.com/drones-are-used-to-monitor-oil-spill-in-tanjung-balau-waters/ |
The present article is an attempt to describe the social evolution of the community of Vershina, a village founded in the beginning of the 20th century by voluntary settlers from Little Poland – from a cultural island to the stage of assimilation. The social, economic, cultural, political and language situation of the community changed several times. The most significant historical moments of Russia and Soviet Union set the borders of three main periods in Verhina’s history. During its first two-three decades Vershina consisted a homogenous Polish cultural and language island. The migrants preserved the Roman Catholic religion, Polish language, traditions, as well as farming methods and machines. Collectivization and the communist system with its repressions made the Polish village assimilate to its surroundings. With the flow of time, the generation of first settlers died and some of the traditions of Little Poland vanished or got modified with elements of the Soviet, Russian or Buryat culture. After Perestroika the minorities gained some rights, which strengthened in the 1990s. Thanks to the political changes and the collapse of the SU the inhabitants of Vershina can found cultural organisations, cultivate their religion and learn Polish in the local schools. However, in spite of the regained rights, over the decades of mass sovietization and ateization, the culture and customs of the Polish community became similar to other Siberian villages. Young people from the group of our interest abandon their mother language, are not eager to leave Russia and move to Poland. The process of assimilation is intensifying while there are practically no factors protecting the local culture and language. | https://depot.ceon.pl/handle/123456789/5875 |
Semiconductor memory is an essential constituent for today’s electronic devices. It’s a kind of device in which digital information is maintained by using IC (Integrated Circuit) technology. These memories are classified on the basis of types of data access and types of data storage and these mechanisms can be categorized in two groups that are volatile RAM (Random Access Memory) and non-volatile ROM (Read Only Memory).
RAM and ROM can be further classified on the basis of technologies and applications available. RAM includes DRAM, SRAM, SDRAM, and MRAM. ROM can be categorized in to PROM, EPROM, EEPROM, Flash memory etc. DRAM, mainstream memory holds a larger market share followed by NAND Flash, 3D ReRAM, NOR Flash. PCRAM is a new technology in the market and possesses better features than conventional memories. It also provides power saving opportunities to customers.
Growing market for smartphones, tablets and SSD (Solid-state drives) are the major growth drivers for the semiconductor memories market. Government regulations and manufacturing standards might restrict the growth of this market as marketers believe that implementation of these regulations and standards might affect the sourcing of materials and increase the cost of products.
Some of the notable companies in this market are Toshiba, SanDisk Corporation, Micron Technology, Inc., Intel, IBM, Fujitsu, Cypress Semiconductor, Samsung, Atmel Corporation, Crocus Technology, Everspin Technology among many others. Samsung and Micron Technology are regarded as leading companies in the R&D of PCRAM technology. SanDisk Corporation is engaged in developing the non-volatile technologies such as phase-change memory, charge-trap flash, memristor and other technologies.
This research report analyzes this market depending on its market segments, major geographies, and current market trends. Geographies analyzed under this research report include
- North America
- Asia Pacific
- Europe
- Rest of the World
This report provides comprehensive analysis of
- Market growth drivers
- Factors limiting market growth
- Current market trends
- Market structure
- Market projections for upcoming years
This report is a complete study of current trends in the market, industry growth drivers, and restraints. It provides market projections for the coming years. It includes analysis of recent developments in technology, Porter’s five force model analysis and detailed profiles of top industry players. The report also includes a review of micro and macro factors essential for the existing market players and new entrants along with detailed value chain analysis. | https://www.transparencymarketresearch.com/semiconductor-memory-market.html |
Between Realms and Protecting Humanity: Free Young Adult eBooks
The Verity (The Verity Book 1) by M. J. Lawrie: Donated to the last human army at birth, Scarlett and her band of misfit friends spend their days killing monsters, protecting humanity, and playing the odd game of zombie-head football. But when she’s ordered to put down her swords and marry a man she hates, Scarlett refuses and discovers a terrible truth about those sworn to protect them.
This book is Free on July 8, 2021
Thanatos (The Underworld Saga Book 1) by Eva Pohler: Thanatos meets seventeen-year-old Therese while she’s in a coma hovering between the realm of the dead and the realm of dreams. A lucid dreamer, she takes control of her dream and kisses him. Death had never been kissed. Now that he has, all hell breaks loose in USA Today bestselling author Eva Pohler’s Greek mythology romance. | https://www.freebooksy.com/2021/07/08/free-young-adult-ebooks-649/ |
After a long day at work, I always look forward to having some “me time”. While I’m always up for activities like Netflix, face masks, or napping (my personal favourite), I also love finding time to intentionally rest in God. I find this practice rejuvenating, and it helps me to step away from the stresses of life. Here for some of my favourite ways to spend time with Him!
Going for a Walk
When I find myself feeling overwhelmed, I love to step away and spend some time outdoors. I’m lucky to live near a forest, and I’ve found that going on nature walks is a great way for me to spend time with God. The quietness allows me to really enjoy and appreciate His creation, and it helps me to quiet my mind and heart to focus on Him. It reminds me of the beauty of the world, and that God is good. You can do this wherever you live, even if it’s just a walk around the block. Take some time to notice and rejoice in the world that God has given us!
Listening to Music
God speaks to us in many different ways. One way I have heard His voice speak clearly to me is through music. I love lighting some candles, putting away any distractions, and playing either a worship or instrumental playlist, and listening to what He has to say to me. Sometimes it’s just a feeling of peace. Other times He gives me a word or a truth from a song to hold onto. Whatever it is, I always leave feeling rested and cared for by Him.
Need some worship music recommendations? Check out the Promise Keeper Playlist.
Writing a Gratitude List
I am not the world’s most optimistic person. Sometimes I find myself feeling hopeless, and I struggle to remember all of the good things in my life. One way I’ve combated this is by writing a daily gratitude list to thank God for all that He has done. It can be filled with big things like getting a new job, making a new friend, or getting into university. But I have also found it’s helped me appreciate the smaller things in life like sunsets, hot chocolate, and rainy days. I like writing my list at night, it helps me to reflect and end the day by praising God.
Want a place to keep your gratitude lists organized? Take a look at the Lane of Roses Gratitude Journal available on Amazon.
Journaling
Journaling is a great way to get down all of your thoughts and prayers to give them to God. Another way I like to journal is by writing out Bible verses and adding different artistic elements and designs to them. I find that this helps me remember the verse, and it adds a fun and creative element to the process. I like to pick verses that help me deal with different emotions I’m feeling. One of my favourites to write out is Philippians 4:6 which says “Don’t worry about anything, instead pray about everything.” When I’m feeling anxious, I just write out the verse, and it helps me to rest in God and feel His peace.
Looking for verses that speak to your specific emotions? Download the Lane of Roses app and check out the section “Verses for Every Emotion.”
Reflection
Reflection activities are a great way to see how God has moved in your life. I often like to look back on old journal entries to see how far I’ve come, and to see the different prayers God has answered. If you’re a visual person, you can also look at old photos to help you remember all that God has done for you.
These are just a few suggestions for you to incorporate into your “me time” with God. Some other ideas include listening to podcasts or sermons, creating some art, or reading your Bible. Be creative, and find something that brings you joy and connects you closer to God! | https://www.laneofroses.com/post/ways-to-rest-in-god-s-promises |
HackMag
Learning to detect shell codes for ARM platform
Shell codes, what are they and what do they do?
Today we are going to talk about one of the types of malicious instructions exploiting remote software vulnerabilities, particularly memory vulnerabilities. Historically, such sets of instructions are called shell codes. Previously such attacks used to grant access to shell, and somehow it became the custom. Typical memory vulnerabilities exploited by shell codes are, first of all, buffer overrun, stock variables and other structures overrun.
Let’s view them in layman’s terms, taking the simplest type as an example. Stack buffer overrun is considered the simplest one. So, shell codes operate as follows. Let’s assume that some vulnerable function working with user data was activated in the code. When it is activated, the stack undergoes several things at once: the return address to the following instruction is kept there (in order to know where the control should be passed to after the vulnerable function ends); ‘BP’ flag value is kept; a specific area for local data is allocated (which in our case is the “user input”). If the number of functions read is not verified, but the malefactor has transferred more data than it is necessary, then this data will replace service values in the stack, both flag values and return address. Where will the control go after the function has been ended? It will go to the very address that now has appeared in the return address area. Thus, the malefactor’s target task is to form the data in such a way in order to pass the control to the malicious load that also resides in the data transferred. Basically, to run a random code on a victim machine.
Traditionally, both shell codes and methods of their detection are usually associated with x86 platform due to the fact that this type of attack is rather old and used to target the most popular platform. The situation has changed for the past several years. ARM-based devices are several times more popular than x86 now and continue growing in number. This means both smartphones and tablets; Google and Samsung are producing ARM-based chomebooks now. ARM architecture (Advanced RISC Machine) is a family of licensed 32bit and 64bit microprocessor cores designed by ARM Limited. ARM presents a processor RISC architecture. Both the platform and shell codes seem to be on several different levels of abstraction. How can platform replacement change the shell code type? The answer is hidden in the number of essential differences between the two platforms which give the malefactors an opportunity to use varied techniques for shell coding.
What was wrong with ARM
The current shell code detection solutions available for x86 platform analyze typical shell code features. Nevertheless, they appear to be inapplicable for ARM platform as the shell code types change. Let’s look at the differences between these two architectures more closely, as they directly influence the shell code types.
Fixed instruction size
Apart from x86 architecture, where the size of instructions varies from one to 16bit, all the instructions in ARM architecture are of fixed size (32bit for ARM mode, 16bit for Thumb).
Due to this ARM feature, the disassembly with different offsets is not synchronized (self-synchronizing disassembly). Self-synchronizing disassembly is a disassembling feature for instructions in x86 architecture. No matter what byte it starts with, there will always be a synchronization point between a random byte disassembly and the beginning of an instruction stream disassembly. This feature simplifies shell code search within the traffic (it may be located randomly in the stream), but makes it harder to run shell code analysis, as there is a risk to miss instructions which are critical for the shell code (see pic. 2).
Pic. 2. Self-synchronizing disassembly
When detecting ARM shell codes within the byte stream it is enough to perform disassembly starting with four offsets from the beginning of the stream: 0, 1, 2, 3. As the instructions are fixed in length, the disassembling process will always start from the beginning of the shell code without skipping important instructions.
Several work modes of the processor and dynamical change among them
We have already mentioned two processor modes. It’s even more complex in reality: besides those two we’ve got Thumb2 (several 32bit instructions were added to 16bit Thumb; such technique allows to increase the opcode density significantly) and Jazelle supporting hardware acceleration for Java byte code.
Thumb mode, in particular, usually was used to make programs to fit in the integrated systems for which limited storage is typical. The use of Thumb under other conditions is not reasonable, as it is slower than ARM mode: it doesn’t support conditional execution, jump prediction module doesn’t perform really well, etc. Due to this fact most applications use ARM mode, but with shell coding the problem of data volume becomes topical issue. That is why dynamic processor mode change is one of the most popular techniques for shell codes. Particularly, It is presented in more than 80% of publicly available templates. An example of a shell code written with different processor modes is shown on pic. 3.
The procedure is as follows. An instruction to change processor mode appears in the shell codes (‘BX Rm’) on the crossing of instruction chain from different processor modes. As the vulnerable program may run in ARM mode, then in order to execute the shell code, the processor has to be switched to Thumb mode. In order to switch the processor to another mode, it is necessary to read the instruction counter register and use its value to jump to the beginning of the shell code with the help of BX Rm instruction, where ‘Rm’ is a general purpose register with the address of the shell code beginning written in. In order to tell the processor which mode it should change to, a value depending on the mode required will be put into the most significant bit of the address.
The instructions from different modes may be located at some distance from one another, but subject to shell code limitations we may assume that offset between the ARM processor mode change code and Thumb shell code will be comparable with the shell code size. An example of such shell code can be seen on pic. 4 (this shell code was taken from exploit-db.com).
The dynamic processor mode changing technique is used in shell codes not only to implement wider functionality into the same size but also for obfuscation as well. Apparently, the process mode change and, respectively, other disassembly will lead to failure in execution of signature approaches on the same template. From the other hand, if you know about this special feature, nobody will prevent you from generating all the possible signatures with processor mode changes taken into account. Nevertheless, nobody has ever focused on this issue.
Conditional execution of instructions
In our opinion it’s one of the most interesting ARM features that introduces another shell code obfuscation method. Each instruction in ARM is executed or ignored by the processor depending on the flag register value. The flag register value for an instruction to be executed is selected through adding a specific suffix to the instruction.
For example, MOVEQ R0, R0 instruction will only be executed with Z = 1 flag (‘EQ’ suffix is used). There exist 15 suffix values. And there is also ‘S’ suffix that indicates whether or not this instruction will change flag register value.
What is this technique for shell codes? First, through this you can reduce code volume significantly (see pic. 5). Second, a new type of obfuscation is now possible: what if we provide an absolutely legitimate program with malicious load only through replacement of flag values with the ones we need? Such a method will obviously hamper the static analysis. For example, one of typical and rather efficient approaches to static analysis is varied analysis of control flow graphs (CFG) and instruction flow graphs (IFG).
Pic. 5. Compaction
Conditional execution doesn’t offer the opportunity to analyze CFG correctly with any method based on CFG analysis, as static analysis doesn’t allow to find out what specific instructions are to be executed and what instructions are going to be ignored. The instruction flow graph won’t display the real structure of the program to be analyzed either, as many nodes of the graph will be ignored by the processor. In other words, we’ve lost one of the most interesting methods of shell code detection (too many articles were dedicated to this method).
Pic. 6. Example for various instruction flows within one code
This feature makes it more difficult to perform dynamic shell code analysis (emulation). The case is that due to conditional execution of instructions it is possible to redirect instruction execution flow in such a way, that the same code will be able to perform absolutely different actions depending on initial distribution of flag values (e.g. an initial flag distribution may initiate a malicious work load). In order to retrieve initial file distribution, the shell code uses flag register value that had been before the control was passed to the shell code, this is the so-called shell code ‘non-selfcontained’ technique.
How does it happen? Let’s look at the example provided on pic. 6. Here we have the same program that was launched twice but with different initial conditions (to simplify the process we’ll discuss only two flags: ZERO and CARRY). We have an instruction block with ‘AL’ suffix at the beginning of the program. This means that all the instructions will be executed despite the number of flags. Then we can see ADDEQS r0, r1 instruction that will only be executed with ZERO = 1 flag, i.e. in the right emulation only. Besides, this instruction will change flag distribution in the right-hand emulation (thanks to ‘S’ suffix). Now we have two blocks: CS: CARRY = 1, and NE: ZERO = 0. Moreover, ‘NE’ block may affect the values of ‘r3’ and ‘r4’ registers, so that the flags will be changed differently in the subsequent ADDCCS r3, r4 instruction (executed in both emulations). Please pay attention that the same instruction will give out different results with different initial emulation conditions. Besides, this instruction will affect possible subsequent instructions. Thus, a hidden instruction sequence is formed being only activated with conditions which are necessary for the shell code.
Well, ARM shell code is extremely crafty to be detected during one emulating procedure. That’s why it’s recommended to perform emulations with all possible initial conditions (there are 15 of them, as many as conditional suffixes). Besides we don’t know where exactly in traffic the shell code is located, so we need to analyze from each offset. These factors together affect “very negatively” the real time performance of traffic analysis.
Direct addressing to instruction counter
ARM architecture allows to address instruction counter directly. This, of course, makes a malefactor’s life much easier. Even ‘GetPC’ code being often used for x80 shell coding is not obligatory now. As you may remember, this technique allows to get register value for instruction counter without direct address to it. ‘Call label’ call instruction is inserted into the shell code on close offset (inside shell code), with ‘pop bx’ stack register picking instruction executed, because ‘call’ instruction keeps return address on the top of the stack. Thus, typical heuristics for x86 shell codes must be modified: now we will seek Get-UsePC code instead of GetPC code.
Get-UsePC code can be understood as reading of ‘PC’ instruction counter values and subsequent use of this value. In order to calculate the instruction counter value you can address ‘PC’ (‘R15’) register directly; you can also activate the function with ‘BL’ instruction and then use the value of ‘LR’ (‘R14’) register with the return address.
The problem lies in the fact that legitimate programs will definitely use GetPC code: it is necessary to return control from (MOV PC,LR or `LDR PC,#Зvalue_from_stack) function. That’s why in order to separate chaff from grain we should also take into account the value of instruction counter register. I.e. we have to find out which registers implicitly refer to the instruction counter and check where they were applied. E.g. if the register was used in a memory reading instruction, then we can confirm that here we have a decrypter, as the reading will be performed with close offset and, subsequently, from shell code workload. An example of such shell code is given on pic. 7 (this shell code was taken from exploit-db.com).
When a function is activated, the parameters are put to registers
Unlike x86 architecture, where the parameters are transferred to functions through the stack, ARM architecture writes the parameters into ‘R0-R3’ registers. If the number of parameters is greater, then the rest of the parameters are put on the stack, as in x86.
So bye-bye, ROP shell codes! Well, of course not really bye-bye… At least this feature will complicate their coding. ROP shell code activates functions from system libraries in order to make malicious workload out of their parts. It’s rather difficult to use this method due to the fact that shell code patterns must contain initialization of parameters into registers. I.e. we can see that rather rare necessary “parts” will become even rarer. Well, at least somebody’s imagination will now not fly so high.
Being an executable code, the object under inspection has the properties which are specific for various OS’s. Particularly, an executable code has to run with OS or core library activations. So, a detector based on search of specific instruction patterns (including system calls and their number count) was typical for x86. Everything is not like that in ARM, again.
The following sequence of actions takes place in ARM to activate a function: the parameters of the function are put to a general purpose register (R0–R3) and to the stack (if the number of parameters is more than four), then ‘BL’ function is activated (‘BLX’ if the function is written with the use of instructions from another processor mode). In order to make ‘svc’ system call, we should upload the system call number to ‘R7’ register and upload the call parameters to general purpose registers (if these parameters are required for a system call).
That’s why in order to detect this attribute we need to use the technique of abstract instruction execution. What is this technique? The code is executed without saving of register values. The only thing that we are able to monitor is which registers have been initialized with specific values. Thus, we must check whether general purpose registers were initialized (and ‘R7’ register for system calls) before a system call or a function activation. E.g. pic. 7 shows the code with system calls initiated (part of Metasploit shell code).
x86 heritage
ARM inherited some shell code features form x86. Thus, detectors for such features may also be left without any significant modifications and on their favorite warm place. Some static shell code features and dynamic decrypter detectors (shell codes are usually obfuscated) may also be referred to them.
NOP trace detection.
As a rule, such detectors analyze correct disassembly of instructions from each offset, that is a typical NOP trace attribute. Just one thing: the number of disassembled instructions is only counted for each processor mode separately, because if instructions from different modes are used in NOP trace, then the control may fall on an instruction using a mode that differs form the current processor mode; then the instruction will be interrupted: unexpected instruction.
Return address is located in the specified value range.
Return address in shell codes is overwritten with a value located within the address range of an executable process. The lower limit of the range is defined by the origin of the overwritten buffer. The upper limit is defined as RA˘SL, where ‘RA’ is the return address field address, and ‘SL’ is the length of a malicious executable code; or as BS˘SL, where ‘BS’ is the origin of the stack. This attribute is general for all the tested objects which don’t use address space layout randomization (ASLR). Detection is modified for no platforms under consideration.
Analysis of number of work load readings and unique memory records.
The detected object may be considered a polymorphic shell code, if these parameters exceed the specified threshold, and control flow at least once is passed from the address space over to the address where a record was performed earlier (pic. 1). The number of readings is not counted in terms of the number of instructions (as ARM supports simultaneous load of several registers at once), but the amount of registers loaded by ‘LDM’ instruction (‘LDR’ instruction can read only one register). Also, decrypted shell code workload is written to close address for shell code decryption. The number of records is counted by the number of registers uploaded to memory with ‘STM’ instruction (‘STR’ instruction can write only one register). After the shell code has been decrypted, we need to pass the control to the decrypted workload (pic. 10), i.e. the address to which the record was done earlier.
Pic. 9. Decryption of shell code work load
Pic. 10. Passing control to the shell code work load
Conclusions
Summarizing everything said above we can make the following conclusion. In our opinion, ARM processor epoch is living a second life. In the nearest future the necessity to protect such systems will become more and more important. As for shell codes… Having scrutinized the differences between these two platforms we now are able to make the following conclusions. First, these differences have partly modified shell codes; second, they allowed malefactors to implement essentially different obfuscation techniques. All this resulted in the fact that the existing detection methods for x86 in case of ARM either break down or may hardly be applicable (e.g. they run longer, much longer). Taking into account the fact that detection speed is limited drastically, the conclusion is disappointing. On the contrary, the difference between these two platforms allows us to find some features which are only specific for ARM shell codes, and that of course is a positive sign. In other words, the development of ARM shell code detector is crucial and possible.
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Trump Pulls Us Out Of Paris Climate Agreement
WASHINGTON The United States will pull out of a landmark global coalition meant to curb emissions that cause climate change, President Donald Trump announced Thursday.
“The United States will withdraw from the Paris climate accord,” Trump said to applause from the crowd gathered in the White House Rose Garden.
He added that the U.S. will begin negotiations to re-enter either the Paris accord or a new treaty on terms that are better for American businesses and taxpayers.
On The Us Withdrawal From The Paris Agreement
Press Statement
Today the United States began the process to withdraw from the Paris Agreement. Per the terms of the Agreement, the United States submitted formal notification of its withdrawal to the United Nations. The withdrawal will take effect one year from delivery of the notification.
As noted in his June 1, 2017 remarks , President Trump made the decision to withdraw from the Paris Agreement because of the unfair economic burden imposed on American workers, businesses, and taxpayers by U.S. pledges made under the Agreement. The United States has reduced all types of emissions, even as we grow our economy and ensure our citizensâ access to affordable energy. Our results speak for themselves: U.S. emissions of criteria air pollutants that impact human health and the environment declined by 74% between 1970 and 2018. U.S. net greenhouse gas emissions dropped 13% from 2005-2017, even as our economy grew over 19 percent.
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Americas Back In The Paris Agreement For How Long
Climate politics is enjoying an optimistic moment, but a Trumpist rerun would be ruinous for environmental diplomacy.
On his first day in office, President Joe Biden signed an executive order for the US to rejoin the Paris Agreement. A new US Nationally Determined Contribution , containing its emission reductions pledge, will be announced as Biden hosts a virtual Climate Leaders Summit on Earth Day, 22 April. Newly appointed US Climate Envoy John Kerry has been engaging leaders in a world tour, underlining the emphasis on climate in the Biden administrations foreign policy priorities.
Around the world, the declaration that Americas back in the Paris Agreement was welcomed by civil society and leaders alike. And the move has isolated climate laggards such as Australia, for whom the Trump administration had provided political cover.
As the US the worlds second-largest emitter and largest historical emitter re-engages in international climate diplomacy, along with a flurry of long-term net-zero targets being set by major economies such as China and Japan, climate politics is enjoying a moment of optimism.
The irony is that the Paris Agreement was designed around US domestic political considerations. The hope was that it allowed enough flexibility for the next US administration to maintain participation.
Main photo courtesy Unsplash user Melissa Bradley
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Just A Tiny Temperature Decrease
Trump also suggested that the Paris Agreement would lead to only a minuscule reduction in global temperature.
“Even if the Paris Agreement were implemented in full, with total compliance from all nations, it is estimated it would only produce a two-tenths of one degree think of that, this much Celsius reduction in global temperature by the year 2100,” he said. “Tiny, tiny amount.”
A detailed analysis of the impact of the Paris goals by Climate Interactive suggests those numbers are off.
The global temperature will rise there is no scenario in which there will be an overall reduction. But let’s assume that Trump meant a reduction from the projections of temperature increases that would happen without the Paris Agreement.
Under a “business as usual” scenario in which past trends continue, the expected temperature increase in 2100 is 4.2 degrees Celsius . If all nations fully achieve their Paris pledges, however, the average global surface temperature in 2100 is expected to be 3.3 degrees. That means the accord would lead to a reduction of nine-tenths of one degree, not two.
Nine-tenths of a degree on a global scale is huge. Since the industrial revolution, global temperatures on average have risen 0.99 degrees Celsius, according to NASA. That’s not so far from .90, and we’re already seeing plenty of dramatic changes around the planet. Even a reduction of two-tenths of a degree would not be “tiny” it would be 20% of the increase we’ve already seen.
Trumps Paris Agreement Withdrawal: What It Means And What Comes Next
Content from the Brookings Institution India Center is now archived. After seven years of an impactful partnership, as of September 11, 2020, Brookings India is now the Centre for Social and Economic Progress, an independent public policy institution based in India.
Editor’s Note:
This post was originally published shortly before President Trump’s announcement on the U.S. withdrawal from the Paris climate accord, anticipating that outcome. It has since been updated to reflect the decision.
Today, President Donald Trump announced that he will withdraw the United States from the landmark Paris Agreement on climate change. It was adopted in 2015 by 195 nations, with 147 ratifying itincluding the United States, which is the worlds second largest greenhouse gas emitter. Experts offer their analyses on what the decision could mean and what comes next.
William Galston: President Trumps advisers may have suggested that withdrawing from the Paris climate accord would be a popular move. This is what they told him about the firing of FBI Director James Comey, and he seems to have believed it. This could become yet another self-inflicted wound, because vast majorities of Americans want to remain in the Paris accord, including many of Trumps own supporters.
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Weve Always Been America First
What Trump can do is remind his supportersâand everyone else on the planetâwhich side heâs on, and, more to the point, which side heâs fighting. Heâs taking a shirts-and-skins stand against liberals, against goo-goos, against condescending scolds in Birkenstocks who donât like Styrofoam or hulking SUVs or real Americans, against naive globalists who want the U.S. to suck up to the French and the Chinese and the United Nations. Climate change will affect the entire earth, from drought-ravaged farm villages in Africa to flood-prone condo towers in Miami, but for Trump itâs just a symbol of the stuff that people who donât like Trump care about. Paris is just an Obama legacy that he can kill, when he doesnât have the votes to kill Obamaâs health reforms or Wall Street regulations or tax hikes on the wealthy. Whatever damage Trumpâs climate policies cause to the planet will be collateral damage, shrapnel from his political war on elites and the left and Obama.
But that wonât make the damage any less real. The United States happens to be located on that planet, and itâs the only known planet with pizza, whether the president wants to protect it or not. The United States is also part of the community of nations, and itâs a community with many common interests, whether the president wants to lead it or not.
Trump Isnt A Climate Denier Hes Worse
The president is withdrawing the U.S. from the Paris Agreement on climate change because he just cant quit carbon.
The United States began the formal process of leaving the Paris Agreement on climate change yesterday, withdrawing on the first day it was legally possible. Barring something unforeseen, the country will depart the accord on November 4, 2020a day after the next presidential election.
If it feels like the Paris withdrawal has been coming for years, thats not wrong. It was already clear on the day he was elected that President Donald Trump would leave the Paris Agreement. After some vacillating early in his term, Trump made a sunny, pomp-dense Rose Garden speech in June 2017 and promised to depart the treaty. But under the agreements terms, he could not formally notify the United Nations of his intent to leave until this week, and American diplomats attended climate negotiations in the interim.
Nearly two and a half years later, its worth briefly remembering that 2017 speech, which ran to more than half an hour. Scott Pruitt, the only other Cabinet official who spoke at the event, resigned from the Environmental Protection Agency amid scandal a little more than a year later. Secretary of State Rex Tillerson and Energy Secretary Rick Perry also attended. The effort to leave Paris has by now survived three chiefs of staff, four national security advisers, and 10 Cabinet secretaries. Trump himself really wants to leave the treaty.
Read Also: What Was The Dow When Trump Was Elected
What Was The Paris Agreement
The U.S. is currently the second-highest greenhouse gas emitter in the world. Its responsible for spewing more than 5 billion metric tons of carbon dioxide a year since 1990, to say nothing of other potent planet-warming gases, such as methane or hydrofluorocarbons.
The country is number one in overall historical emissions, however: the source of 25 percent of all human-produced greenhouse gases that have collected in the atmosphere since the Industrial Revolution.
After years of negotiations, signatories to the Paris Agreement decided to try to limit the amount of global warming at the end of the century to less than 2 degrees Celsius and to aim for an even more ambitious target of 2.7 degrees Fahrenheit . Passing these thresholds, mountains of science suggested, would result in catastrophic changes to the climate system that would have dangerous, costly outcomes for billions of people across the planet. Since the Agreement, a steady stream of research has shown that even the lower temperature goal is likely to spur unwelcome effects. Many of those are already apparent, from supercharged tropical cyclones to record-breaking wildfires.
The goals werent legally binding, but there was great international political pressure to cooperate, says , an analyst at Climate Analytics. Much of that pressure was generated by the commitments from the United States: As the primary driver of emissions, the countrys willingness to participate held great weight.
Four Reasons Trump Should Withdraw From Paris Climate Agreement
As Earth Day passes, there is a game of tug-of-war going on in the White House.
As Earth Day passes, there is a game of tug-of-war going on in the White House. One side is advising President Donald Trump to forgo his campaign promise to withdraw from the Paris Climate Agreement . Theyd instead like to see Trump cut a better deal to remain in the agreement. The other side is encouraging the president to keep his commitment to pull America out of the PCA, leaving other countries to follow their own self-destructive path and America ascendant.
Each side is arguing its position is the best way to help Make America Great Again, but the stay in Paris side is 100 percent wrong. Here are four strong reasons why:
First, the Paris Climate Agreement is a bad deal for United States. In fact, the treaty is so bad President Barack Obama didnt dare submit it to the Senate for ratification as the Constitution requires because he knew it had no chance of passing. Instead, he tried to do an end run around the Constitution, by implementing the agreement in bits and pieces through executive orders.
Fossil-fuel production sparked a job boom in oil and gas fields in numerous states, including North Dakota, Ohio, Pennsylvania, Texas, and West Virginia. The low-cost energy this boom produced brought manufacturing jobs, especially in the chemical industry, back home from overseas.
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What Is Trumps Climate Legacy
Trumps decision to pull out of the landmark accord was the first major step in his campaign to systematically roll back US federal climate policies set up during the administration of Barack Obama.
Trump has since reversed dozens of climate-related regulations, including rules on air pollution, emissions, drilling and oil and gas extraction. During his first term as president, and in his re-election campaign, he made no secret of his preference for fossil fuels and the industry which provides them. A report by the US energy department, released last month, lauds oil and gas as providing energy security and supporting our quality of life, without mentioning climate risks related to persistent use of carbon-rich fuels.
The hard truths of climate change by the numbers
Although the United States played a major part in crafting the climate agreement, it will be the only one out of the nearly 200 parties to pull out of the pact.
Pulling Out Of Paris Will Harm The Poor In The Us And Abroad
Anthony Janetos, Director, Frederick S. Pardee Center for the Study of the Longer-Range Future and Professor of Earth and Environment, Boston University
Details on precisely what President Trumps decision to pull the U.S. out of the Paris accord on climate change means and how this decision will be implemented are lacking, but it was already clear that the United States had little intention of meeting its emissions goals. The proposed dismantling of the Clean Power Plan to limit carbon emissions from power plants would essentially ensure that outcome.
But pulling out of Paris also means the U.S. will refuse to make any additional contributions to the U.N. Green Climate Fund. The fact that the worlds largest economy and the largest per capita emitter will decline to take on policies to curb greenhouse gas emissions and simultaneously refuse to contribute to a fund largely devoted to adaptation measures in the worlds poor countries is dangerous and unprecedented.
The impacts of climate change are not hypotheticals to be worried about far in the future. The last several IPCC reports the international scientific assessments on climate change done through the U.N. have made it abundantly clear that impacts are happening now. And even more recent science has shown that the probabilities of even individual extreme weather events can be attributed to climate change.
Also Check: What Republican Is Running Against Trump
What Are The Paris Agreement’s Costs
Theres a lot of misinformation out there about the Paris Agreement, including the idea that it will hurt the U.S. economy. That was among a number of unfounded claimsformer president Trump repeated, arguing that the accord would cost the U.S. economy $3 trillion by 2040 and $2.7 million jobs by 2025, making us less competitive against China and India. But as fact checkers noted, these statistics originated from a debunked March 2017 study that exaggerated the future costs of emissions reductions, underestimated advances in energy efficiency and clean energy technologies, and outright ignored the huge health and economic costs of climate change itself. Climate change is already costing public health. Research from NRDC scientists shows how inaction on climate change is responsible for many billions in health costs each year in just the United Statesas communities around the world experience greater displacement, illness, famine, water shortages, civil strife, and death.
Finally, rather than giving China and India a pass to pollute, as Trump claimed, the pact represents the first time those two major developing economies have agreed to concrete and time-bound climate commitments. Both countries, which are already poised to lead the world in renewable energy, have made significant progress to meet their Paris goals.
M. Frustino/Associated Press
Dear Mr President: Letters On Climate Change
President Trump said the other 195 countries in the agreement went wild, they were so happy” that the U.S. initially joined the accord “for the simple reason that it put our country, the United States of America which we all love, in a very, very big economic disadvantage.”
The Paris Agreement which was brokered in 2015 and took effect in November 2016 seeks to prevent increases in global temperatures by gradually reducing man-made emissions that science has shown causes rising temperatures. The accord sets as a specific goal keeping the Earth from warming by more than 3.6 degrees Fahrenheit or 2 degrees Celsius.
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United States Withdrawal From The Paris Agreement
|This article is part of a series about|
On June 1, 2017, United States President Donald Trump announced that the U.S. would cease all participation in the 2015 Paris Agreement on climate change mitigation, contending that the agreement would “undermine” the U.S. economy, and put the U.S. “at a permanent disadvantage.”
In accordance with Article 28 of the Paris Agreement, a country cannot give notice of withdrawal from the agreement within the first three years of its start date in the relevant country, which was on November 4, 2016, in the case of the United States. The White House later clarified that the U.S. will abide by the four-year exit process. On November 4, 2019, the administration gave a formal notice of intention to withdraw, which takes 12 months to take effect. Until the withdrawal took effect, the United States was obligated to maintain its commitments under the Agreement, such as the requirement to continue reporting its emissions to the United Nations. The withdrawal took effect on November 4, 2020, one day after the 2020 U.S. presidential election.
Trump’s decision to withdraw the U.S. was backed by many Republicans but was strongly opposed by Democrats. Trump’s decision to withdraw was strongly criticized in the U.S. and abroad by environmentalists, some religious organizations, business leaders, and scientists. A majority of Americans opposed withdrawal.
Why Trump Actually Pulled Out Of Paris
It wasnât because of the climate, or to help American business. He needed to troll the worldâand this was his best shot so far.
Donald Trumpâs decision to withdraw from the Paris climate agreement was not really about the climate. And despite his overheated rhetoric about the âtremendousâ and âdraconianâ burdens the deal would impose on the U.S. economy, Trumpâs decision wasnât really about that, either. Americaâs commitments under the Paris deal, like those of the other 194 cooperating nations, were voluntary. So those burdens were imaginary.
No, Trumpâs abrupt withdrawal from this carefully crafted multilateral compromise was a diplomatic and political slap: It was about extending a middle finger to the world, while reminding his base that he shares its resentments of fancy-pants elites and smarty-pants scientists and tree-hugging squishes who look down on real Americans who drill for oil and dig for coal. He was thrusting the United States into the role of global renegade, rejecting not only the scientific consensus about climate but the international consensus for action, joining only Syria and Nicaragua in refusing to help the community of nations address a planetary problem. Congress doesnât seem willing to pay for Trumpâs border wallâand Mexico certainly isnâtâso rejecting the Paris deal was an easier way to express his Fortress America themes without having to pass legislation. | https://www.trumpreporter.net/why-did-trump-withdraw-from-paris-agreement/ |
By Joe Desjarlais
Why is the idea of “partnership” important to understand?
The word “partnership” has been used often lately but this means different things to various groups.
In Canada, the national consensus is shifting away from ignorance and marginalization, and towards the affirmation of historic and contemporary Métis identities across Canada. Courts are affirming the constitutionality of Métis identities, Senate reports, and more recently a Special representative tasked with Métis issues, have opened up opportunities for meaningful dialogue, and the Federal Liberals are now talking about nation-to-nations relations with historic Métis communities.
While there are detractors and naysayers, it is evident that there is a movement to rebuild self-determining, self-sufficient, and self governing Métis communities and ‘nations’. Perhaps most exciting for lasting and sustainable social change, is the growing awareness that the ‘history of Canada’ must be the story of indigenous nations as ‘partners’.
How do you respond to the contests to control Metis identity?
I recently read on social media that a Conservative MP wants Minister Carolyn Bennett to say what constitutes the Métis Nation. The acrimonious public debate has reached into almost every area of public debate including universities, where professors have had sharp disagreements, and into the blogosphere, where there have been angry social media exchanges.
There is a ‘culture war’ over Métis identity and the politics of it has been rather nasty; the war in the trenches is being fought in academic departments in Canada with some having a vested interest in ethnogenesis and the need to restrict Métis identity based on the ‘politics of rights.’ The dominant narrative forwarded by these ‘charter’ groups tends to consolidate Métis identity into a single national paradigm or marginalize Métis peoples in a footnote to the past. On the other hand, there are voices, ones that have been excluded from recognized Métis political organizations, that are attempting to expand the definition to suit their own special interest. For example, a group claiming Métis status has recently been conducting DNA studies to ‘prove’ their Métis-ness.
The polarities that are developing imply that these are the only two options if we are to move into a new era of reconciliation. But overcoming the either/or conundrum and offering a model of mutual recognition that can work for all Métis nations in Canada is the exact reasons why we at the BCMF work at the Federation to educate people about a relational history and the importance of a “partnership.”
What message would you convey to those involved in angry public social media disputes about identity politics?
You can’t have ‘identity’ without reciprocity (ie: mutual recognition). Interestingly, it could well be argued that existing Métis representation, including Métis National Council, has contributed to this problem because of their exclusive claims to being Métis. It seems the only response to alternative claims for Métis nationhood is to ‘exclude’ all others. If these different Métis organizations were open to ‘many ways of being Métis’ they could get on with the business of supporting other communities that have legitimate claims to Métis sovereignty. But in order to do this, of course, the leaders of these organizations would have to stop playing the politics of recognition. When they break from using a contest for a limited number of rights as a form of legitimacy we may be able to get beyond the basic premises that guide their one-winner-take-all strategy.
Perhaps dialogue and cooperation would be more appropriate as a way of bringing wellbeing to Métis nations in Canada?
What are some challenges these groups with claims to ‘being Metis’ will have to answer going forward?
I noticed that Eastern groups, who have been marginalized from the national organization claiming exclusive rights to being Métis, have made ‘treaties’ with a new national Métis organization. This new organization is attempting to regulate individual Métis identity by setting up yet another national ‘registry’. However, this does not demonstrate a different way of thinking from that of the organization they are fighting against. Limitations and problems surface when groups adopt a racial discourse and go down the road of “ethnogenesis” and “biological origins’ to define and regulate members through ‘individual rights bearing Métis citizenship criterion’. When Métis organizations adopt the standard Canadian academic theory of “ethnogenesis” as a way of defining an origin for Métis nations, they inevitably lead their constituents into a fight over Métis identity politics. To close membership based exclusively on blood, or ancestry, infringes on the notion of sovereignty and creates all kinds of logistical hurdles that do not have solutions.
These groups will all eventually have to answer “how does one determine nationhood” (who defines it and acts in its self-interest)? and “what happens when Métis communities were disintegrated via government colonial policy”?
Usage of the term “Metis” in history anecdotally is far different than a community or nation demonstrating from the historical record that they were acting in their own ‘self-interest,’ as when the Manitoba “Treaty” was negotiated.
Key words in identifying a historically constitutive Métis nation would be self-determination (with the ability to decide who has ‘citizenship’), self-sufficiency (with a land base and specific unique economic interests), and self-government (with relations of power, including laws, customs, material cultures, and an ability to defend sovereignty). In relation to the current debate on Métis identity, one of the most important elements of nationhood is not the amount of indigenous blood flowing through one’s veins but the ability for legitimate historic Métis communities to define their own citizenship.
What role does research play and why is it important as Metis communities reconstitute?
The notion of ‘being Métis’ has developed in Canada to service a particular political purpose. Funding and research models, the political structures and the policy incentives for indigenous peoples have supported a particular understanding of being Métis.
If the movement toward reconciliation is also ensuring the autonomy and well-being of Métis communities and nations, however, then historic Métis nations need to start acting as equal partners. By respecting each other we can all engage in a national conversation that can bring about mutually beneficial outcomes. In order for this nation-to-nation conversation to emerge, however, Métis communities need to gather their intellectual resources and establish clear research agendas. To build sustainable nations all across Canada, we must be well informed about industry engagement, land-use histories, cultural resource practices, and invest in things like social and language recovery projects.
Communities and nations that are caught without the capacity to generate knowledge capital, which is the ability to construct our own narratives of partnership out of the primary sources of our own unique past, will be disadvantaged and unable to creatively respond to the challenges that lay ahead. Investing in a knowledge network will not happen organically; it must be an intentional strategy with enough rigour built in to challenge the dominant perspectives put forward by existing Métis institutes, the traditional academic establishment, and government policies. Imagine the powerful impact that a “made by Métis” research platform would have for Métis communities and nations, whether responding to ‘identity politics’, or advocating for Metis children in communities, or arguing at the highest levels of the Supreme court!
The BC Métis Federation recognizes the power of knowledge networks. We are currently exploring short, medium and long term strategic research plans and are investigating the possibility of a “research division”, a ‘hub’ where community members, researchers, academics, corporations, governments and others can contribute to specific projects.
We acknowledge the importance of a coherent Métis national research strategy and the eventual need to establish a ‘research endowment’ so that our efforts are sustainable and can contribute to nation-to-nation dialogues that will be open, dynamic and continuous. The BCMF knows that gathering, producing and sharing knowledge is essential to the long-term viability of Métis nations, and our intellectual resources must be available as a vital part of our community engagement, repatriation and revitalization.
What are some important national research themes coming into focus?
In a spirit of dialogue and cooperation we are beginning to look at three specific research themes and timeframes:
Research Focus #1: The Political Philosophy of Louis Riel and other Metis Leaders: Developing a research specialization in Metis political thought and specifically the notion of a pluralistic association as represented in the Manitoba Treaty of 1870 (with broader interpretations for all Metis communities in Canada). Research Focus #2: Metis Diaspora and Kinship Communities: Establish research specialty in the various unique self-determined communities, especially in the Pacific Northwest, where there is opportunity to explore the many different ways of being Métis in Canada. Research Focus #3: Metis Reconciliation: Justice for Riel and for ‘Riels people’. The “just” conclusion to the life and memory of Louis Riel in Canada is important to Metis. A national project of this scope is also very important to many others, including the Canadian Association of Retired Teachers, an organization with over 137,000 members which has recently provided written support for this initiative.
Any final words?
Going forward we have to have capacity for renewal and repatriation in BC and elsewhere.
It might start from the recovery of customs, the reconstitution of family kinship, and the clear demonstration of the many ‘sovereign communities’ that lived together. Metis political organizations and mainstream governments and industry will have to come to this awareness and move out of the idea of limiting and regulating Metis identities through identity politics.
The BCMF is initiating a resurgence of the historical Metis definitions of “kinship,” and advocating for Métis nations that have a sense of belonging, a clear sense of self- determination, evidence of historical difference, and the desire to live in shared relations. Rather than interpreting Métis history by its relationship to Canada, we call for Métis histories that are informed by our own shared concepts of self-determination and historical difference. Strong, equal and ongoing partnerships can only flourish and be sustained if this knowledge is utilized to provide land and resources that can become the foundation for inextinguishable sovereignty and generational sufficiency. We believe in the possibility of many Métis communities coming together as independent self-sustaining nations and we are confident in the hope that partnerships that seek the welfare of one “another” can abolish, once and for all, the winner-take-all mentality that is responsible for our marginalization and subjugation. | https://bcmetis.com/news/unpacking-partnerships-and-knowledge-capital/ |
The evidence of giants has always been discredited by mainstream archeology. However, the latest findings show that they are a reality that they cannot hide.
A group of researchers found possible remains of a Neolithic giant civilization in China, which developed around the Yellow River basin.
The group of Chinese archaeologists carried out excavation work in the eastern province of Shandong. There they discovered some disproportionately large human remains.
A civilization of giants in China?
They are believed to belong to a civilization that lived in the vicinity around 5,000 years in the past, according to information from the TASS agency.
According to the researchers, the approximate height of these people, according to the remains, should far exceed the average height of the inhabitants of the area. These must have been around one meter ninety high.
They may have belonged to the Longshan Neolithic civilization, which developed in the vicinity of the Huang He River. Popularly known as the Yellow River.
Fang Hui is the press officer of the Center for Cultural and History Studies at Shandong University. He declared that they have concluded, after analyzing the remains found, that this civilization could be considered as true giants.
Much more developed
He also stated that in addition to the extremely large remains, abundant food sources were also found. Many older than the rest of the inhabitants of nearby areas.
This finding was possible thanks to excavations carried out in the Jinan city area, which began in mid-2016.
To date, experts have discovered around 100 buildings, 200 different tombs, and at least 20 sacrificial pits.
It has also been determined that the ancestors of the current Chinese who lived in eastern parts of the current territory of the country about 5000 years ago were much more developed .
Signs of remarkably advanced agriculture were found, as well as other types of activities such as the cultivation of cereals and even organized livestock.
It is not the first time that evidence has been found of ancient civilizations much more developed than the rest and with physical features that significantly differentiate them. For the most part, its large size being remarkable compared to the rest.
Are we witnessing a pattern? Because of the more developed tribes they were much taller? We could be talking about the direct descendants of the giants. | https://mysteriousociety.com/giants-in-china-evidence-they-walked-among-humans |
Our aim is to foster a life-long love of learning by embedding planning in meaningful contexts. Learning should be irresistible. Our curriculum aims to deliver a Twenty First Century education covering all elements of the 2014 National Curriculum which will equip our children with the skills required to be independent learners. We aim to deliver this by:
- Nurturing enthusiasm for teaching and learning:
- Knowing that learning is fun.
- Establishing cross-curricular links, contexts for learning to foster a broader and deeper understanding.
- Where necessary holding a flexible timetabling approach to make space for depth of study.
- Develop social skills and encourage children to become more active citizens within the school community.
- Optimising opportunities for speaking and listening.
- Building up children’s confidence and motivation to learn through the use of a range of learning and teaching styles. By providing opportunities for children to apply knowledge and learning in practical ways.
- Embedding foundation subjects in engaging contexts for learning
- Awareness of children’s developmental needs and providing an age appropriate curriculum in our Learning Teams
Although links can be made with all subjects, other subjects are taught as dedicated, discrete sessions:
- Numeracy – Maths skills are key to developing everyday skills although links can be made to the curriculum through data handling, position, and measurement, especially in Science, DT and Geography.
- Aspects of Literacy – Phonics, Guided Reading and Handwriting are taught as discrete subjects as they build up basic skills.
- RE – in accordance with the school’s RE policy and Bradford Agreed Syllabus although links with topics are made where appropriate.
- PE and Swimming
- MFL – French – links are made with contexts for learning where appropriate.
Curriculum Planning/Contexts for Learning
We have incorporated the National Curriculum objectives into our planning. Rigour and progression is ensured through the use of our own curriculum planning booklets which cover National Curriculum objectives for each subject and identify progressive skills for learning.
Long/Medium Term Planning
Long and medium term planning identifies the contexts for learning (themes and the number of weeks for the duration of the theme).The long term plans for each theme identify the relevant objectives which are highlighted in each year group’s curriculum planning book as the objectives are covered.
Teachers use the objectives and translate them into meaningful activities for the children using the most suitable learning sequence. We record our medium term planning as a learning sequence which incorporates;
- Formative assessment of children’s understanding using KWL grids whereby children demonstrate ownership of their learning and direction in their learning.
- How the theme will be introduced (e.g. a visit film or atefact)
- Opportunities for trips and visitors
- What the learning outcome will be –this could be an artefact/museum/book/film etc
Resources
Each theme/context for learning is resourced where possible with a box containing an inventory
Leaders of Learning and Coordinators review resource needs annually and order as necessary
We also value visits and visitors and use them where appropriate
Assessment and Recording.
We assess understanding by using statements based on the National Curriculum objectives.
Subject co-ordinators collect evidence (data, photographs, work) from year groups to compile a portfolio that allows them to assess how well their subject is being delivered. This is overseen by the SLT.
Governors are kept informed of developments and priorities through communication between their link classteacher, and where appropriate the subject co-ordinator.
Parents and carers are kept informed of developments, through our Induction Day consultation evenings, end of year reports, and half termly year group newsletters.
Monitoring and Review.
The Head / Deputy and leaders of learning are responsible for monitoring and reviewing the curriculum through;
- Observation of lessons
- Scrutiny of Aire Loom books. | https://www.saltaireprimaryschool.co.uk/website/learning_and_curriculum/131825 |
“I first knew about my sight problem when I was nine years old. Slowly my difficulty of seeing from a distance and near objects became worse in school as well as at home.” – Billal, Primary School, Ethiopia.
In April 2016, Our Children’s Vision was launched with the ambitious goal of reaching 50 million children with vision services by 2020. In 2018, through the hard work of our 79 partner organisations in 55 countries, the half-way milestone for this ambitious project was met and passed ahead of schedule.
Now I can sit anywhere in the classroom as the other students. I am very happy with my eyesight and last semester I was ranked 1st in my class.
With about 90% of the world’s vision impaired living in developing countries, the burden of lost productivity and the economic and social consequences fall heavily on the most vulnerable. These include millions of children living with vision impairment. Reaching these children, especially those living in rural or remote locations, with trained professionals who can assess their vision is a massive challenge that is global in scale. It is the challenge that Our Children’s Vision was established to meet.
By starting Our Children’s Vision we saw a chance to not just help today’s children, but to reduce global levels of uncorrected vision impairment in future generations – but we knew that we couldn’t do it alone.
By giving children access to vision correction, we are empowering them to achieve their full potential at school, but we are also hoping to give them access to a better future and ultimately to reduce inequalities and poverty in their country.
Around the world governments have recognised schools as not just centres of education, but as access points for delivering health services to children. However, these health services have rarely included even basic vision tests. This is why as some partners are visiting schools, others are meeting with health and education officials, and still others are performing the basic research that will enable programs and ensure their successful implementation.
Vision issues can negatively impact a child’s development and performance in school. Ensuring that these children are identified, have access to and receive quality eye care, and have access to prescribed treatments makes a tremendous impact today and beyond childhood.
There are many players involved when it comes to eradicating avoidable blindness among school children – particularly adults within a child’s inner circle. Teachers can be skilled to recognise and diagnose basic eye problems, parents can be educated to identify uncommon behaviour and know how to access care. They can be at the front lines of ensuring children receive the eye care they need.
It isn’t just children in schools who are in need of eye care. Sadly, there are millions of children who are not enrolled in a school system. We all work to ensure those children do not fall through the cracks, that they are not left behind. | https://www.essilorseechange.com/the-vision-of-27-million-children/ |
Identify and assess compliance issues, implement effective controls, monitor day-to-day regulatory quality at the transaction level. Has responsibility for the Fund’s accounting and financial planning and reporting.
KEY RESPONSIBILITIES
- Efficient management of depositor payouts, depositor claims and resolution in case of Bank failure;
- Performance reports and records of contributing Institutions;
- Oversee financial operations of the Fund;
- Custody and proper management financial records of all Fund investments;
- Establish financial accounting, reporting and budget management systems;
- Conduct analysis of financial risks and benefits on business initiatives and strategy;
- Coordinate creditors’ meetings in case of liquidation;
- Coordinate general meetings of members during liquidation;
- Ensure compliance with legislative requirements relating to financial matters;
DUTIES
1. Oversees efficient depositor payout of protected deposits, Manages depositor claims & resolution in case of Bank failure;
2. Reviews the depositor payout manual to ensure it is up to date and operational;
3. Ensures proper depositor records are kept in all contributing institutions to facilitate depositor payout process if a need arises;
4. Oversees the implementation of Depositor Unique Identifiers (Single Customer view);
5. Proposes decisions on the conduct of procedure and mode of payment of insured deposits in case of a bank’s bankruptcy or liquidation;
6. Oversees site examinations of Contributing Institutions with the purpose of monitoring, analyzing, and strengthening the financial condition;
7. Analyzes Onsite and offsite reports on the performance of Contributing Institutions from Bank of Uganda and advise Chief Executive Officer;
8. Oversees the conduct of simulations for depositor payout;
9. Cooperates with international organizations and institutions in connection with deposit insurance, and gets familiar with the deposit insurance systems in other countries;
10. Determines the methodology for measurement and calculation of the potential risk of the Deposit Insurance Fund at a bank and the entire banking sector level;
11. Determines the standards for banks’ reporting on deposits and placements;
12. Furnishes reports to the Bank of Uganda concerning the settlement of banks’ obligations for payment of deposit insurance premium, for each bank individually;
13. Ensures accurate payments are received and penalties are issued to defaulting institutions;
14. Establishes and periodically tests the collective software solution to support depositor payout;
15. Notifies depositors and other stakeholders about the deposit insurance, determines visual appearance and format of the information material, prints and distributes brochures, posters and leaflets to banks, etc.;
16. Participates in meetings with Bank of Uganda and other regulatory authorities regarding the problem and troubled Contributing Institutions including informational meetings, financial assistance, and make recommendations to the CEO;
17. Ensures the Cash Book and General Ledger are always up-to-date;
18. Ensures that monthly reconciliations are undertaken in respect of all the Fund’s accounts and balance sheet control Accounts;
19. Ensures custody and proper financial records of all Investments;
20. Oversees preparation of Fund financial Statements and ensures timely financial reporting;
21. Ensures fixed asset register is properly maintained;
22. Coordinates external and Internal Audit activities;
23. Ensures successful implementation of IFRS9 and compliance to all International Accounting Standards (IAS) and International Financial Reporting Standards;
24. Establishes and periodically tests financial accounting and reporting as well as Budget management systems
25. Leads on financial fraud prevention and detection and to annually report on such matters;
26. Implements recommendations on the operation of the financial control systems and other matters by Internal and External Auditors;
27. Oversees preparation of DPF Annual Work Plans and Budget and ensure that they are monitored;
28. Participates in activities of liquidation and recoveries procedures of banks and contributing institutions in accordance with legal regulations;
29. Works with Information Technology department to develop, implement and improve systems for payroll management and depositor payouts. | https://careers.dpf.or.ug/staff/michael-l-mayanja/?team_cpt=template-resumepackages |
Vietnam’s Ministry of Health on Tuesday announced a fine of more than VND5.8 billion (US$260,000) against Philippine beverage firm URC for producing and selling products with high lead content.
The ministry said URC Vietnam, a unit of Philippine producer Universal Robina, is punished for breaking food safety regulations with a batch of green tea C2 manufactured on February 4, 2016 and a batch of energy drink Rong Do produced on November 10, 2015.
Test results showed that the products from these batches have lead content from 0.053 to 0.085 mg/l, above the permitted limit of 0.05 mg/l.
The company was ordered to recall the batches from the market earlier this month. But a large number of affected bottles worth VND3.9 billion ($174,200) had already been sold and could not be retrieved, according to local media reports.
Inspectors also said two of URC's warehouses failed to meet food safety regulations, with spoilt products being stored next to those for sale.
The fine announced Tuesday showed that the Ministry of Health chose to stand by its own findings regarding the quality of the company's bestselling products, following various and conflicting results released by other local testing agencies.
The case, apparently one of the biggest food safety scandals in Vietnam in years, caught the attention of the public and the press after some social media posts accused the Philippine producer of bribing some quality control officers to modify test results and clear their products.
There have also been claims that some journalists from various media outlets chose to ignore the company's serious violations.
The health ministry has also identified three other batches of URC products with high lead content and ordered a recall. No cash fine has been imposed on these three batches, possibly because the ministry is still trying to determine the exact number of tainted bottles.
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The Forbidden City (Imperial Palace) at the heart of Beijing is the largest and most complete imperial palace and ancient building complex in China and the world at large.
The Temple of Heaven in southern Beijing is China's largest existing complex of ancient sacrificial buildings. Occupying an area of 273 hectares, it is three times the area of the Forbidden City.
Situated in the northwest suburbs of Beijing, the Summer Palace is the largest and best-preserved royal garden, and one of the four most famous gardens in China.
Built in 1505 during the Ming Dynasty, Badaling is one of the most important sections of the Great Wall. Located in Yanqing County, 70 km from Beijing's city proper, Badaling is also the most frequented section of the Great Wall by visitors since the Ming Dynasty.
Located in the Dongcheng District of Beijing, Lama Temple (Yonghe Temple) is the largest lamasery in Beijing.
The Ming Tombs are located on the southern hill of Tianshou Mountain. The place was chosen by the third Ming Dynasty emperor, Yongle (1402–1424), who moved the national capital from Nanjing to Beijing, China's current capital.
Zhoukoudian lies 50 kilometers to the southwest of Beijing proper, and is the former resting place of Peking man, a Homo erectus pekinensi.
Located in the center of Beijing City, northwest of the Forbidden City, Beihai Park is one of the oldest, largest and best-preserved ancient imperial gardens in China.
Located inside Fucheng Gate in Beijing, the temple was built in 1096 during the Liao Dynasty. Miaoying Temple, also named the White Dagoba Temple, got its name because there is a white dagoba in the temple.
Originally built in 1306, Guozijian, also known as the Imperial Academy, was the highest educational institute in ancient China during the Yuan (1271-1368), Ming (1368-1644) and Qing (1644-1911) dynasties. | http://www.china.org.cn/travel/cultural_relics/node_7157266.htm |
Rye is a cereal grown in colder parts of northern and central Europe and Russia. It is mainly used for animal feed, but is also used to make breads and crispbreads. Rye contains gluten-forming proteins and is therefore not suitable for gluten-free diets.
The dough produced by rye flour is less elastic than wheat dough, and the breads therefore tend to be heavy and flat unless the rye flour is mixed with wheat to aid leavening and lighten the color. Rye bread may be made by standard bread-making methods, or by sourdough processes whereby starter doughs containing lactic acid are added to the flours. These give a distinctive flavor to the dough. Pumpernickel is a dark rye bread made from coarse grain by a sourdough process, with a long baking time that ensures that it keeps for a long time.
Rye crispbreads are made from whole meal or flaked rye, mixed with water or milk. The dough may be fermented with yeast to make brown crispbread, or unfermented (white crispbread). The nutrient value of crispbreads depends on the ingredients, but will be similar to the whole grain if this was used. They are commonly regarded as low energy foods – partly because they are light. However, weight for weight, crispbreads are more energy and nutrient dense than bread because of their low water content.
Rice
Rice is a cereal that needs to be grown in water to give the best yields. It is the second most important staple crop in the world: most of the yield (about 90%) is used as the main food in the country of growth and never enters the world markets. When harvested, rice grains are enclosed in a bull, which is removed in the first stage of milling to produce brown or wholegrain rice. Brown rice contains all the minerals and vitamins of the grain as well as some dietary fiber and it is therefore a useful food, despite needing longer cooking times than the more highly milled white rice which has the germ and brats removed. White rice is still a useful source of carbohydrate and energy: protein content is not high but it has a good pattern of amino acids. White rice is low in thiamin and other B vitamins, and in countries where white rice is the staple, supplemented by few other foods, has led to the development of the thiamin deficiency disease, beriberi. This was commonly seen in Japanese prisoners of war during the Second World War. Parboiling of rice prior to milling it to white rice distributes the vitamins and minerals through the grain, and has been used as a preventative measure.
Rice is often classified by grain length, and described as long, medium, or short grain. The different types have different culinary uses: long grain rice is usually boiled in water and eaten with savory dishes: short grain rice is used for milk puddings. In Mediterranean cooking rice with round short grains is used for making “risotto”.
Rice bran is commonly used as animal feed, but some is now also sold as a source of dietary fiber for those who cannot tolerate wheat.
Wild rice is not strictly rice, but rather the seed of an aquatic grass that grew wild in lakes in the north of the USA and south of Canada. The grain is now grown for the world market, and provides elongated shiny black-brown grains that have a nutty flavor and chewy texture when cooked. The grain is nutritious, having a higher protein and B vitamins content than cereals generally but it is usually eaten in smaller quantities. Rice and wild rice are both gluten free. | https://www.vitamins.biz/rye-rice/ |
Gleis 21 was planned in a participatory manner with the future residents, including everything from the urban development to the power outlets. The property is located in the Sonnwendviertel, in the center of the new “Leben am Helmut Zilk Park” development near Vienna Central Station (“Hauptbahnhof Wien”). The co-housing project was designed as a compact, zero-energy house (“Niedrigstenergiehaus”) in a wood-hybrid construction and was built in a way that minimized the use of resources.
An important part of the concept of Gleis 21 is the open ground floor, which is accessible to everyone in the quarter. It is designed to be permeable and creates a connection between the promenade and the park. This open space is formulated as an extension of urban space. The so-called “neighborhood wall” (“Nachbarschaftswand”) becomes a communication area with the neighborhood. Event dates are posted here, an open bookcase is provided, and there is space for exchange and interaction.
There are four commercial areas on the ground floor and basement. An event room and a media studio are used by the Gleis 21 cultural association, among others, and a restaurant area forms the urban edge to the Helmut-Zilk-Park. A sunken courtyard facing the promenade opens onto a music school on the basement level.
The 34 residential units on the four upper floors are accessed through an open portico on the north-west side of the building. This is not only used to access but is also designed as a leisure area and for socialization.
Due to the neutral and flexible basic structure of the building, the residential units could be planned individually with the users, and they each have a south-east-facing private balcony. One of the units is shared as a guest apartment. In addition, five “flex units” are made available to refugees as apartments.
There are three free-standing pavilions on the top floor, all of which are shared: the “Ruhehaus” (rest house) with a library, the “Gemeinschaftshaus” (community house) with kitchen and playroom and the “Entspannungshaus” (relaxation house) with a sauna, bathtub and meditation room. The open spaces on the roof invite residents to plant a garden, grill or sunbathe.
The selection and detailed planning of the common rooms responded to the needs of the group. In addition to the private living spaces, the extensive shared areas offer spaces for shared and individual use and represent the focus of the communal aspect of the project: from the communal kitchen to the library and sauna on the top floor to the workshop, studio, laundry room and fitness room in the basement.
The residential project Gleis 21 and its housing group are based on three principles: “living in solidarity”, “enjoying properly” and “creating through media”. Solidarity is promoted in many ways, from mutual neighborhood help to a solidarity fund for situations of personal distress. It is also sought in the form of the “flex units”, the costs of which are covered by the residents and which are offered to refugees in cooperation with the “Diakonie Flüchtlingsdienst”.
The cooperation with the radio station “Radio Orange”, the TV-station “Okto TV” and the movie theater “Stadtkino Wien” helps to shape the cultural, media and social life of the quarter. The media workshop is connected to the event room, which can also be rented, and can be outfitted as required.
The cultural association Gleis 21 organizes a regular cultural program tailored to the area with appealing theater performances, readings, workshops and concerts. The restaurant, which is oriented towards the park, is currently being used by an artists’ collective that runs a cafe there. The music school in the basement enhances the cultural possibilities in the quarter. | https://urbannext.net/gleis-21-zero-energy-co-housing-project/ |
Canadian Water Network is Canada’s trusted broker of research insights for the water sector. When decision makers ask, ‘What does the science say about this?’ They frame what is known and unknown in a way that usefully informs the choices being made. Their unique approach begins with an in-depth understanding of the problem and identifying where progress can be made. They talk to the experts and consult the knowledge base to frame the knowns and unknowns. From there, they communicate relevant insights to practice and policy leaders, moving the conversation forward.
Their History
Canadian Water Network was established in 2001, in response to Walkerton’s deadly drinking water crisis. Over the next 16 years, the organization invested more than $100 million in water research as a Network of Centres of Excellence. Today, the organization is an independent nonprofit that serves decision-makers across the water sector. | https://www.devex.com/organizations/canadian-water-network-142355 |
BACKGROUND OF THE INVENTION
SUMMARY OF THE INVENTION
DESCRIPTION OF THE EMBODIMENTS
First Embodiment
Second Embodiment
Other Embodiments
1. Field of the Invention
The present invention relates to an image display apparatus and a control method for the image display apparatus.
2. Description of the Related Art
In an image display apparatus including a backlight including a plurality of light-emitting blocks, light emission brightness of which can be individually controlled, there is a technique for reducing the light emission brightness of the backlight for each of the light-emitting blocks according to an input image signal. There is also a technique for reducing the light emission brightness of the backlight for each of the light-emitting blocks according to an input image signal and correcting an image signal of an image region corresponding to the light-emitting block according to the reduction of the light emission brightness. These techniques are called local dimming. By using the local dimming, it is possible to improve the contrast of a display image and suppress a misadjusted black level (see, for example, WO2009/054223).
In the conventional local dimming, the light emission brightness is controlled according to an input image for each of the light-emitting blocks to, when a maximum gradation value of an image region corresponding to each of the light-emitting blocks of the backlight is low, reduce the light emission brightness of the light-emitting block and, when the maximum gradation value is high, increase the light emission brightness. A pixel value (a gradation value) of the image region corresponding to the light-emitting block, the light emission brightness of which is reduced, is extended to prevent the display brightness of pixels in the image region from changing with respect to the brightness of the input signal. In this way, the light emission brightness of the light-emitting block is determined according to the maximum gradation value of one image region corresponding to the light-emitting block. Therefore, when the maximum gradation value of the image region greatly changes, the light emission brightness of the light-emitting block also greatly changes. This sometimes causes a flicker.
In WO2009/054223, by determining the light emission brightness of a light-emitting block on the basis of a weighted average of a maximum and an average of the brightness of pixels in an image region corresponding to the light-emitting block, a flicker is further suppressed compared with determining the light emission brightness on the basis of only the maximum. However, in the method of WO2009/054223, when the weight of the average in calculating the weighted average is larger than the weight of the maximum, the display brightness of the pixels having the maximum sometimes falls below the brightness of an input signal.
Therefore, the present invention provides a technique capable of suppressing a flicker in an image display apparatus that performs local dimming and suppressing deterioration in reproducibility of brightness.
According to a first aspect of the present invention, there is provided an image display apparatus including: a light-emitting unit, a light emission amount of which is variably controllable; a display unit configured to display an image by modulating, according to imago data, light emitted from the light-emitting unit; and a control unit configured to control the light emission amount of the light-emitting unit according to a maximum and a minimum of a pixel value in a frame. The control unit maximizes the light emission amount of the light-emitting unit irrespective of the maximum when the minimum is larger than a first threshold.
According to a second aspect of the present invention, there is provided a control method for an image display apparatus including: a light-emitting unit, a light emission amount of which is variably controllable; and a display unit configured to display an image by modulating, according to image data, light emitted from the light-emitting unit, the control method including: acquiring a maximum and a minimum of a pixel value in a frame; and controlling the light emission amount of the light-emitting unit according to the maximum and the minimum. In the controlling the light emission amount of the light-emitting unit, the light emission amount of the light-emitting unit is maximized irrespective of the maximum when the minimum is larger than a first threshold.
According to the present invention, it is possible to suppress a flicker in an image display apparatus that performs local dimming and suppressing deterioration in reproducibility of brightness.
Further features of the present invention will become apparent from the following description of exemplary embodiments (with reference to the attached drawings).
A liquid crystal display apparatus and a control method for the liquid crystal display apparatus according to a first embodiment of the present invention are explained below. The liquid crystal display apparatus according to this embodiment includes a backlight including a plurality of light-emitting blocks, light emission brightness (a light emission amount) of which is variably controllable individually. The blocks are regions obtained by dividing a screen. For example, the blocks are regions obtained by dividing the screen into N (N is an integer equal to or larger than 2) in the horizontal direction and M (M is an integer equal to or larger than 2) in the vertical direction. The blocks may be regions obtained by dividing the screen only in the horizontal direction or may be regions obtained by dividing the screen only in the vertical direction.
FIG. 1
is a block diagram showing an example of the functional configuration of the liquid crystal display apparatus according to this embodiment.
1
2
1
2
3
Input image data (image signal) is sent to a maximum detecting unit and a minimum detecting unit . The maximum detecting unit acquires, for each of image regions corresponding to the blocks, a maximum of pixel values (gradation values) of pixels in the image region. The minimum detecting unit acquires, for each of the image regions corresponding to the blocks, a minimum of the pixel values of the pixels in the image region. The maximum and the minimum of the pixel values for each of the blocks are sent to a backlight control value determining unit .
3
3
1
5
1
5
3
4
5
FIG. 2A
The backlight control value determining unit determines a backlight control value for each of the blocks from the maximum and the minimum of the pixel values of each of the blocks. The backlight control value corresponds to the light emission brightness of the backlight. The backlight control value determining unit determines the backlight control value according to a two-dimensional table shown in . In this embodiment, the backlight control value is set according to a plurality of light emission levels decided according to light emission amounts. The light emission level takes any value among five stages of a level to a level . The light emission brightness is the smallest at the level . The light emission brightness increases as the level rises. The light emission brightness is the largest at the level . The backlight control value determined by the backlight control value determining unit is sent to a backlight and a correction coefficient calculating unit .
4
4
6
3
6
4
The backlight is a lighting device including a plurality of blocks. Each of the blocks includes one or a plurality of light sources. The backlight irradiates a liquid crystal panel from the back. The light emission brightness of each of the blocks can be independently controlled. The light emission brightness of each of the blocks is controlled according to a signal (a backlight control value) output by the backlight control value determining unit . The liquid crystal panel transmits light emitted from the backlight at transmittance determined for each of pixels, whereby an observable image is displayed on the screen.
6
4
6
7
5
7
7
5
3
The liquid crystal panel displays an image by modulating, according to image data, the light emitted from the backlight . Image data is input to the liquid crystal panel via a correction processing unit . A correction coefficient calculated by a correction coefficient calculating unit is input to the correction processing unit . The correction processing unit corrects the image data on the basis of the correction coefficient. The correction coefficient calculating unit calculates a brightness distribution of the backlight on the basis of a signal (a backlight control value) output by the backlight control value determining unit and corrects, on the basis of the brightness distribution, the image data such that the brightness of transmitted light is brightness corresponding to a pixel value of the input image data.
FIG. 2A
The two-dimensional table shown in is explained in detail.
6
In the image display apparatus in this embodiment, a relation (a gradation brightness characteristic) between an output brightness value (a display brightness value) L of the liquid crystal panel and an input signal (a pixel value) S is indicated by the following expression when it is assumed that the gradation of the pixel value is 8 bits (0 to 255 gradations):
L=K
W
K
S/
γ
1
1
5
5
where, K represents a display brightness value obtained when the backlight control value is the level and a liquid crystal input pixel value is 0 gradation and W represents a display brightness value obtained when the backlight control value is the level and the liquid crystal input pixel value is 255 gradation. γ represents a gamma value of the image display apparatus and is 2.2 in this embodiment.
1+(5−1)×(255) (Expression 1)
1
2
3
4
5
When control gains Gx at the respective backlight control value levels x are represented as G=0.067, G=0.2, G=0.33, G=0.67, and G=1, an input signal S′ and a display brightness value L at each of the levels are indicated by the following expression:
L=Gx×{K
W
K
S′/
γ
5+(5−5)×(255)}
5
5
where, K represents a display brightness value obtained when the backlight control value is the level and the liquid crystal input pixel value is 0 gradation.
(Expression 2)
A brightness range displayable by the image display apparatus when the input signal is changed between 0 and 255 at each of the backlight control value levels is calculated from Expression 2. A gradation range corresponding to the displayable brightness range is calculated from Expression 1.
5
5
1
2
3
4
5
For example, when it is assumed that W=1 and K=0.005, the displayable brightness range in the case of the backlight control value level is calculated as 0.000335 to 0.067 from Expression 2. A gradation range corresponding to the brightness range is calculated as 0 to 74 from Expression 1. Similarly, a gradation range corresponding to the brightness range displayable at each of the backlight control value levels (hereinafter referred to as displayable gradation range) is 10 to 122 at the level , 13 to 154 at the level , 19 to 212 at the level , and 23 to 255 at the level .
If the block is caused to emit light at the backlight control value level at which both of the minimum and the maximum of the pixel values of the pixels in the image region corresponding to the block are included in the displayable gradation range, it is possible to display all the pixels in the image region corresponding to the block at correct brightness.
In the case of this embodiment, displayable gradation ranges respectively corresponding to the five backlight control value levels overlap one another. Therefore, depending on a combination of the maximum and the minimum, in some case, there are a plurality of backlight control value levels at which the brightness of all the pixels in the image region corresponding to the block can be correctly displayed. On the other hand, depending on a combination of the maximum and the minimum, in some case, there could be no backlight control value level at which both of the minimum and the maximum are included in the displayable gradation range.
Therefore, in this embodiment, a backlight control value level of each of the blocks is determined as explained below on the basis of a maximum and a minimum of pixel values of pixels in an image region corresponding to the block.
(A) A backlight control value level is selected at which the maximum is included in a displayable gradation range and a portion common to a displayable gradation range and a range from the minimum to the maximum is the widest.
(B) When there are a plurality of backlight control value levels that satisfy the condition (A), a maximum backlight control value level among the backlight control value levels is selected.
By determining the backlight control value level as explained above, it is possible to suppress the display brightness of a pixel, a pixel value of which is the maximum, in the image region corresponding to each of the blocks from becoming low with respect to the pixel value. Therefore, it is possible to suppress deterioration in brightness reproducibility.
FIG. 2A
FIG. 2A
FIG. 2A
The two-dimensional table shown in shows a relation between a combination of a maximum and a minimum of pixel values of pixels in an image region corresponding to a block and a backlight control value level that satisfies the above conditions. By selecting a backlight control level from the combination of the maximum and the minimum of the pixel values on the basis of , it is possible to determine a backlight control value level that satisfies the two conditions. In , the ordinate represents the minimum and the abscissa represents the maximum. Since the minimum does not exceed the maximum, a region painted in black in the lower left half of the table does not have a value.
FIG. 2A
FIG. 2B
FIG. 2A
FIG. 2B
As shown in , in this embodiment, the light emission brightness of the block is determine on the basis of not only the maximum but also the minimum of the pixel values of the pixels in the image region corresponding to the block. It is seen that, when the minimum is larger than a certain threshold, a backlight control value of the block is set to a maximum level irrespective of the maximum. The threshold in this case is a lower limit value of a gradation range displayable when the block is caused to emit light with the backlight control value set to the maximum level. For example, even between blocks having an equal maximum, the light emission brightness of the blocks is higher as a minimum is larger. Conventionally, the light emission brightness of the block is determined on the basis of only the maximum. Therefore, the blocks having the equal maximum always have the same light emission brightness. In , such a determination method of light emission brightness of a block in the related art is represented as a two-dimensional table same as for comparison. As shown in , in the relate art, a backlight control value level is determined on the basis of only the maximum. Therefore, if the maximum is the same, the determined backlight control value is the same irrespective of which value the minimum is.
FIGS. 3A to 3F
FIGS. 3A to 3F
1
2
A specific example of the determination method for a backlight control value in this embodiment is explained with reference to . In , T and T represent continuous frames.
FIG. 3A
shows an input image.
FIG. 3B
FIG. 3C
shows maximums of pixel values of pixels in image regions corresponding to blocks of the input image. shows minimums of the pixel values of the pixels in the image regions corresponding to the blocks of the input image.
FIG. 3D
FIG. 3A
FIG. 3B
FIG. 2A
shows backlight control value levels of the blocks determined according to the maximums shown in and the minimums shown in on the basis of the table shown in .
FIG. 3E
FIG. 3A
FIG. 2B
shows the related art for reference and shows backlight control value levels determined according to only the maximums shown in on the basis of the table shown in .
FIG. 3F
FIG. 3A
FIG. 3F
FIG. 3D
FIG. 3E
shows a backlight brightness distribution on an A-A′ cross section shown in obtained when the blocks of the backlight are caused to emit light according to the determined backlight control value levels. In , a solid line indicates the present invention (based on ) and a broken line indicates the related art (based on ).
FIG. 3A
FIG. 2A
FIG. 3F
1
2
5
1
2
In a second block from the left in a first row in , the maximum greatly changes (from 120 to 255) in T to T. However, the minimum does not change (from 120 to 120). Since the minimum is large, the backlight control value level determined by the two-dimensional table shown in is the level in both of T and T. There is no change between the frames. Therefore, as indicated by the solid line in , a brightness change is small between the frames and a flicker less easily occurs.
FIG. 3F
On the other hand, when a backlight control value level is determined according to only a maximum as in the related art, the backlight control value level greatly changes from 2 to 5 according to a change of the maximum. Therefore, as indicated by the broken line in , a brightness change is large between the frames. This causes a flicker.
FIG. 2A
FIG. 2B
FIG. 2A
5
When showing this embodiment and showing the related art are compared, in , an area of the backlight control value level is wider. In more cases than in the related art, when the minimum is large to a certain degree, the backlight control value level does not change even if the maximum and the minimum change. That is, since a change in the light emission brightness of the block is suppressed, it is possible to suppress a flicker.
FIG. 2A
In this embodiment, the backlight control value levels are five levels. However, the backlight control value levels are not limited to this and may be set finer. When the backlight control value levels are finer, a change in light emission brightness at the time when the backlight control value level changes decreases. Therefore, it is possible to more effectively suppress a flicker. Even when the backlight control value levels are set finer, a flicker involved in a change of the maximum and the minimum of the pixel values is suppressed by increasing a ratio of the highest backlight control value level on the table as shown in .
As explained above, according to this embodiment, the light emission brightness is controlled according to the minimum and the maximum of the pixel values of each of the blocks such that a change in the backlight control value level involved in a change in the maximum and the minimum decreases. Therefore, it is possible to realize local dimming with a flicker suppressed. Since a backlight control value level at which brightness of a pixel, a pixel value of which is the maximum, is displayable is selected, it is possible to suppress deterioration in brightness reproducibility.
In a second embodiment, an example is explained in which a flicker is further suppressed with respect to a change in a minimum and a maximum of pixel values of each of blocks.
FIG. 4
8
3
8
is a block diagram showing an example of the functional configuration of a liquid crystal display apparatus according to this embodiment. Components having functions same as the functions in the first embodiment are denoted by the same reference numerals and explanation of the components is omitted. The second embodiment is different from the first embodiment only in that a backlight control value LPF unit is added in a post stage of the backlight control value determining unit . The LPF represents a low pass filter and the backlight control value LPF unit operates as a time LPF.
2
1
3
8
8
A minimum output from the minimum detecting unit , a maximum output from the maximum detecting unit , and a backlight control value output from the backlight control value determining unit are input to the backlight control value LPF unit . The backlight control value LPF unit outputs the backlight control value subjected to time LPF processing.
8
The backlight control value LPF unit is explained below.
3
FIG. 2A
A backlight control value is determined by the backlight control value determining unit on the basis of the two-dimensional table shown in according to a minimum and a maximum of pixel values of each of blocks. When the minimum and the maximum of the pixel values greatly change according to a change of an input image, the backlight control value sometimes greatly changes. For example, when a maximum 50 and a minimum 5 change to a maximum 220 and a minimum 40, a backlight control value level greatly changes from 1 to 5.
8
8
8
The backlight control value LPF unit suppresses a sudden change in the backlight control value. Specifically, the backlight control value LPF unit stores a backlight control value of the preceding frame and compares a backlight control value determined anew in the present frame and the backlight control value of the preceding frame. When an amount of change in the backlight control value level is larger than a threshold Th, the backlight control value LPF unit reduces the change amount to be equal to or smaller than the threshold Th.
For example, when it is assumed that the threshold Th is 1, the backlight control value of the preceding frame is 1, and the backlight control value determined anew in she present frame is 5, a difference between the backlight control values is 4, which is larger than the threshold Th (=1). In this case, the change amount is reduced to 1. The backlight control value level applied to the present frame is changed to 2. A threshold for determining whether processing for reducing the amount of change in the backlight control value in this way is performed is hereinafter referred to as change amount threshold (second threshold). In this embodiment, when the amount of change in the backlight control value is larger than the change amount threshold, the backlight control value applied to the present frame is changed (corrected) such that the amount of change in the backlight control value is equal to or smaller than the change amount threshold (equal to or smaller than the second threshold).
8
8
8
In this embodiment, further, the backlight control value LPF unit varies the threshold according to whether the change in the backlight control value level is involved in the change in the maximum or the change in the minimum and according to whether the change is an increasing change or a decreasing change. Specifically, when the maximum increases or the minimum decreases, the backlight control value LPF unit sets the backlight control value to quickly change. When the minimum increases or the maximum decreases, the backlight control value LPF unit sets the backlight control value to slowly change.
This is because, concerning pixel values of each of the blocks, even if the minimum of the present frame increases with respect to the minimum of the preceding frame, if the maximum does not increase, pixels of the present frame can be displayed at the backlight control value level of the preceding frame. That is, an influence on brightness reproducibility is small even if an increase in the backlight control value level is delayed with respect to the increase in the minimum. Similarly, concerning the pixel values of each of the blocks, even if the maximum of the present frame decreases with respect to the maximum of the preceding frame, if the minimum does not decrease, pixels of the present frame can be displayed at the backlight control value level of the preceding frame. That is, an influence on brightness reproducibility is small even if a decrease in the backlight control value level is delayed with respect to the decrease in the minimum.
8
8
8
8
8
Specifically, the backlight control value LPF unit stores the minimum and the maximum of the preceding frame concerning the pixel values of each of the blocks. When an increase amount of the maximum is larger than a threshold (a third threshold) or a decrease amount of the minimum is larger than the threshold (the third threshold), the backlight control value LPF unit sets the change amount threshold Th to Th_high. When the increase amount of the maximum is equal to or smaller than the threshold (equal to or smaller than the third threshold) or the decrease amount of the minimum is equal to or smaller than the threshold (equal to or smaller than the third threshold), the backlight control value LPF unit sets the change amount threshold Th to Th_low (<Th_high). When both of the increase amount of the maximum and the decrease amount of the minimum are equal to or smaller than the threshold (equal to or smaller than the third threshold), the backlight control value LPF unit uses the change amount threshold (the second threshold) of the preceding frame as it is. When the amount of change in the backlight control value of the present frame with respect to the preceding frame is larger than the change amount threshold, the backlight control value LPF unit sets, as a backlight control value applied to the present frame, a value obtained by adding the change amount threshold to the backlight control value of the preceding frame. Consequently, when the amount of change in the backlight control value is large, change speed of the backlight control value is reduced. When the change in the backlight control value is involved in a large increase in the maximum or a large decrease in the minimum, the backlight control value changes at high speed while being reduced.
8
4
5
The change amount thresholds Th_high and Th_low are not limited to integer values and may be fractional values. The backlight control value LPF unit calculates the backlight control value as a fractional value and retains a value of the preceding frame. A backlight control value obtained by converting the fractional value into an integer value (by, for example, rounding-off) is sent to the backlight and the correction coefficient calculating unit .
FIGS. 5A to 5D
FIGS. 5A to 5D
1
4
A specific example is explained with reference to . In , T and T represent continuous frames.
FIG. 5A
shows an input image.
FIG. 5B
FIG. 5C
shows maximums of pixel values of pixels in image regions corresponding to blocks of the input image. shows minimums of the pixel values of the pixels in the image regions corresponding to the blocks of the input image.
FIG. 5D
shows backlight control value levels determined concerning the blocks.
In this embodiment, the threshold of the maximum change is set to 30, the threshold of the minimum change is set to 5, the change amount threshold Th_high of the backlight control value is set to 1, and the change amount threshold Th_low of the backlight control value is set to 0.4.
FIGS. 5B to 5D
FIG. 2A
1
2
3
5
1
2
3
5
8
3
8
In an upper left block surrounded by a circle in , the maximum does not change (from 160 to 160) and the minimum changes (from 15 to 120) in T to T. When a backlight control value is determined on the basis of the table shown in , the backlight control value of the block changes from the level to the level in T to T. Since this is an increase in the minimum, the change amount threshold Th of the backlight control value is Th_low=0.4. Since the amount of change in the backlight control value is 2 from the level to the level , the change amount is larger than the change amount threshold Th_low. Therefore, a value 3+0.4=3.4 obtained by adding the change amount threshold Th_low to the backlight control value of the preceding frame is set as a backlight control value of the present frame. A backlight control value output from the backlight control value LPF unit is calculated as the level by rounding off 3.4. However, the backlight control value LPF unit stores the value 3.4 obtained by adding the change amount threshold Th_low to the backlight control value of the preceding frame.
2
3
3
5
8
2
5
8
3
4
3
5
3
8
1
4
8
FIG. 2A
FIG. 2A
Both of the maximum and the minimum or the block do not change in T to T. Therefore, the change amount threshold Th remains at Th_low =0.4. Since the maximum is 160 and the minimum is 120 in the block, the backlight control value determined by the backlight control value determining unit on the basis of the table shown in is the level . The backlight control value LPF unit compares the stored backlight control value 3.4 in the preceding frame T and the backlight control value of the present frame. In this case, a change amount (5−3.4=1.6) of the backlight control values is larger than the change amount threshold Th_low (=0.4). Therefore, the backlight control value LPF unit sets, as a backlight control value of the present frame T, a value (3.8) obtained by adding the change amount threshold Th_low (0.4) to the backlight control value (3.4) of the preceding frame. A backlight control value to be output is a value 4 obtained by rounding off the calculated value (3.8). Further, in T, the maximum and the minimum of the block do not change from those in T. A backlight control value determined on the basis of the table shown in is the level . Since the backlight control value of the preceding frame T stored in the backlight control value LPF unit is 3.8, a change amount is 1.2, which is larger than the change amount threshold 0.4. Therefore, a value 4.2 obtained by adding the change amount threshold 0.4 so the backlight control value 3.8 of the preceding frame is a backlight control value of the present frame. A value 4 obtained by rounding off the backlight control value is output. Therefore, the backlight control value of the block in the frames T to T is changes to 3, 5, 5, and 5 if LPF processing by the backlight control value LPF unit is not performed. However, since the LPF processing is performed, the backlight control value slowly changes to 3, 3, 4, and 4.
FIGS. 5B to 5D
1
2
On the other hand, in a lower left block surrounded by a square in , the minimum does not change (from 20 to 20) and the maximum increases (from 20 to 250) in T to T. Since this is an increase in the maximum and an increase amount (250−20=230) of the maximum is equal to or larger than the threshold (30), the change threshold Th of the backlight control value is set to Th_high=1.
2
5
4
1
1
2
5
FIG. 2A
FIG. 2A
A backlight control value of T determined on the basis of the table shown in from the minimum (20) and the maximum (250) is the level . A change amount 1 from the level , which is a backlight control value of the preceding frame T, is equal to or smaller than the change amount threshold . Therefore, processing for reducing the backlight control value is not performed. A backlight control value of the frame T remains at the value determined on the basis of the table shown in , that is, the level .
According to this embodiment, when a slow change in a backlight control value causes a brightness fall (insufficiency of brightness) and gradation collapse, for example, when the maximum increases or the minimum decreases, changing speed of the backlight control value is less easily reduced. Consequently, the brightness fall and the gradation collapse are suppressed. Otherwise, a sudden change in the backlight control value is further suppressed than in the first embodiment. Therefore, it is possible to more effectively suppress a flicker.
As explained above, according to this embodiment, light emission brightness is controlled according to the minimum and the maximum of the pixel values of each of the blocks such that a change in a backlight control value level involved in a change of the maximum and the minimum decreases. Therefore, it is possible to realize local dimming with a flicker suppressed. Since a backlight control value level at which brightness of a pixel, a pixel value of which is the maximum, is displayable is selected, it is possible to suppress deterioration in brightness reproducibility.
1
2
The embodiments are examples in which the present invention is applied to the image display apparatus in which the backlight includes the plurality of light-emitting blocks and a light emission amount can be variably controlled independently for each of the light-emitting blocks. However, the present invention can also be applied to an image display apparatus having a configuration in which the backlight is not divided by light-emitting blocks. In this case, the control in the embodiments can be applied without any modification, on the premise that the number of divisions by the light-emitting blocks of the backlight in the embodiments is 1. In this way, in the case of the image display apparatus that performs brightness control of the backlight uniformly over the entire screen, the maximum detecting unit and the minimum detecting unit detect a maximum and a minimum of pixel values in a frame of image data. By applying the present invention to such an image display apparatus, the effects of a reduction in a flicker and suppression of deterioration in brightness reproducibility are obtained. The embodiments are examples in which the present invention is applied to the image display apparatus including the liquid crystal panel. However, the liquid crystal panel is an example of a display panel. In the image display apparatus of the present invention, the display panel is not limited to the liquid crystal panel.
Embodiments of the present invention can also be realized by a computer of a system or apparatus that reads out and executes computer executable instructions recorded on a storage medium (e.g., non-transitory Computer-readable storage medium) to perform the functions of one or more of the above-described embodiment(s) of the present invention, and by a method performed by the computer of the system or apparatus by, tor example, reading out and executing the computer executable instructions from the storage medium to perform the functions of one or more of the above-described embodiment(s). The computer may comprise one or more of a central processing unit (CPU), micro processing unit (MPU), or other circuitry, and may include a network of separate computers or separate computer processors. The computer executable instructions may be provided to the computer, for example, from a network or the storage medium. The storage medium may include, for example, one or more of a hard disk, a random-access memory (RAM), a read only memory (ROM), a storage of distributed computing systems, an optical disk (such as a compact disc (CD), digital versatile disc (DVD), or Blu-ray Disc (BD)™), a flash memory device, a memory card, and the like.
While the present invention has been described with reference to exemplary embodiments, it is to be understood that the invention is not limited to the disclosed exemplary embodiments. The scope of the following claims is to be accorded the broadest interpretation so as to encompass all such modifications and equivalent structures and functions.
This application claims the benefit of Japanese Patent Application No. 2013-102286, filed on May 14, 2013, which is hereby incorporated by reference herein in its entirety.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1
is a block diagram showing an example of the functional configuration of a liquid crystal display apparatus according to a first embodiment;
FIGS. 2A and 2B
3
are diagrams for explaining a two-dimensional table of a backlight control value determining unit ;
FIGS. 3A to 3F
are diagrams for explaining an operation in the first embodiment;
FIG. 4
is a block diagram showing an example of the functional configuration of a liquid crystal display apparatus according to a second embodiment; and
FIGS. 5A to 5D
are diagrams for explaining an operation in the second embodiment. | |
The effect of a thigh tourniquet on the incidence of deep venous thrombosis after operations on the fore part of the foot.
We performed a prospective randomized clinical study to determine whether use of a thigh tourniquet influences the incidence of deep venous thrombosis. The lower limbs of patients who were scheduled for elective surgery on the fore part of the foot were randomized and assigned to one of three treatment categories: Group I, no tourniquet; Group II, exsanguination by an Esmarch bandage before tourniquet application; and Group III, exsanguination by elevation of the extremity prior to application of a tourniquet. The 117 limbs of seventy-one patients included in this study were evaluated preoperatively and twenty-four and seventy-two hours postoperatively with 125I-labeled fibrinogen, and preoperatively and seventy-two hours postoperatively with Doppler ultrasound studies and phleborheography. The findings in all of the Doppler ultrasound studies and all of the phleborheograms were normal. Two of the 125I-fibrinogen studies were positive, but subsequent contrast venography revealed that these were false-positive findings. We therefore concluded that the use of a thigh tourniquet does not increase the risk of deep venous thrombosis in patients who have had an operation on the fore part of the foot.
| |
Happy to announce that our team @APeacebuilding won the 2018 @USAID #CLA4Dev prize! Big congrats to our #Myanmar colleagues. We are just getting started!
This case describes a CLA approach in a highly conflict-affected region of northern Myanmar between 2013-16. A CLA approach was desirable in this area because it has highly fluid security, political, and humanitarian dynamics, and because access is restricted to international actors, and requires that all interventions are based on local knowledge and agency. The challenge that this case addressed was how local communities can sustainably drive their own peacebuilding and development outcomes with minimal international support, and in the midst of unpredictable and changing local dynamics. Using a methodology developed specifically for locally led change in complex environments – Systemic Action Research (SAR) – a consortium of local organisations designed and implemented activities that directly benefited more than 17,000 people and achieved several notable firsts, including the first ever provision of mine risk education to internally displaced people in this area, the introduction of anti-drug messaging in school curricula, legislative changes away from punitive and towards rehabilitation strategies for drug users, and the initiation of a track 2 dialog forum to support Myanmar’s peace process. Continuous learning, pause and reflect, and adaptive management processes as part of SAR formed the backbone of this initiative, which generated considerable insights for Adapt Peacebuilding, and lessons learned to share with the global peace and development communities. Lessons learned concerned factors that enable CLA approaches, as well as inhibitors, principally related to trust and uncertainty, which strain relations with donors and partners, and can constrain impact.Read More
Systemic Action Research for Peacebuilding
Systemic Action Research for Peacebuilding. A presentation in Colombia about Myanmar experience in bottom up peacebuilding methods.Read More
Systemic conflict assessment of Myanmar's Kachin conflict
Systemic conflict assessment of Myanmar's Kachin conflict. Politics, identity, history, natural resources. Reflects a more optimistic time.Read More
Practical strategies for systems change in complex peacebuilding environments
This article argues that the distinctions we make in peacebuilding masks a messier, highly interdependent reality that we need to honestly engage with. We argue for a more holistic, systems view, and present three case studies of explicitly systemic peacebuilding strategies from Myanmar and Thailand. Reflection on these case studies offers insights for systemic theories of change, including engaging multiple parts of the system in parallel, rewiring relationships within the system, balancing adaptation and control, and building trust with donors to balance risk.Read More
Unpacking the complex causality so-called religious violence in Myanmar
A significant sub-system within the system relates to tensions between different religious and/or ethnic communities resulting from a lack of trust and positive interaction.
There are four important feedback loops which constitute this sub system. The first (R10) , is characterized by the fact that hate speech against Muslims (that employs stereotypes of Muslims as violent) reinforces the perception among non-Muslims that Islam is an inherently violent or aggressive religion. This perception in turn leads people to interpret social or inter-personal conflicts or crimes as religious conflicts (since they assume that Muslims are more likely to be aggressors and/or Islam to be incompatible with other religions). This contributes to the perception that religious conflict is rife, that Islam per se is the cause of the conflicts and/or that non-Muslims are at risk from attack by Muslims, which often results in hate speech against Muslims…Read More
Peacemaking effectiveness: what can Myanmar learn from thirty years of international experience in peace process implementation
This work was produced and distributed ahead of the May 2017 national dialog process of Myanmar's peace process. Based on international comparative evidence drawn from the Kroc Institute for International Peace Studies Peace Accords Matrix, the animation addressed contemporary peacemaking challenges in Myanmar.Read More
Innovating new forms of public participation in peace processes in the midst of war, BuildPeace 2017
This short talk presented to the BuildPeace 2017 Conference in Bogota describes the process and outcomes from implementing systemic action research in Myanmar. The presentation argues that by taking a systems view and empowering local communities in conflict settings to be the agents of change according to the priorities that they themselves define, peacebuilding efforts can be more scalable and sustainable. A recipe for effective bottom up peacebuilding and testament to often overlooked capacities of local communities to articulate and implement peacebuilding better than outsiders can.Read More
Can Myanmar’s peace process learn from international experience? | https://adaptpeacebuilding.org/blog?category=Conflict+research |
A games studio in Leeds are looking to bring in a Junior Games Designer on a permanent basis. The 25 strong studio are known for their specialism in VR/AR game production for established IPs, on console and mobile.
As a Games Designer, you will report to the Head of Game Design. This creative role comes with significant responsibility in design and production across multiple titles that the studio are looking to release.
Ideally, you will have some experience within a game studio or similar industry, however, this company are also considering entry level candidates fresh out of university. Any understanding of Unity, VR/AR/XR, UX Design or other gaming software would be hugely desirable.
The studio is slowly bringing back staff to their office, and as such this role will start out remotely with the view to being more studio based when the current situation starts to level out.
If you feel like you tick the boxes above and would like to know more about the finer details of the role, then get in touch for a confidential chat about your situation. | https://www.campaignlive.co.uk/jobs/job/15667947/junior-game-designer/?LinkSource=SimilarJobPlatform |
When mercury, a global pollutant, enters the aquatic environment, microorganisms can transform it into methylmercury, a compound that is more toxic at low doses than elemental mercury. Once methylmercury is in the environment, it becomes part of the food chain. Small aquatic organisms ingest it from their surrounding environment, and are, in turn, eaten by fish and other, larger aquatic organisms. As a result, the methylmercury biomagnifies, becoming increasingly concentrated as the pollutant works its way up the food chain, polluting marine mammals, birds, and other animals that consume fish. Generally, higher concentrations are found in larger and older animals. Methylmercury pollution also harms the health of people who regularly eat fish. Testing fish and human hair for mercury is a good indicator of mercury pollution levels in various geographic regions and communties.
(2018) A new study has found elevated levels of toxic mercury in women of child-bearing age in countries across the Pacific, Caribbean, and Indian Ocean. More than half of all women who were sampled measured above the US EPA level of concern, and three out of four women measured had mercury levels that have been associated with the onset of mercury-related impacts to fetal development. The study establishes that mercury pollution has accumulated across the worlds’ major oceans, contaminating the marine food chain and posing a threat to a sizable portion of the world’s island populations.
See the report,, as well as an executive study, infographic, press release and video here.
(2017) New research, Mercury in Women of Childbearing Age in 25 Countries, was undertaken to measure the prevalence of mercury body burden at levels that can cause neurological and organ damage. Mercury in a mother’s body can be transferred to her fetus during pregnancy, exposing the developing fetus to the potent neurotoxin.
The study is the first of its kind to sample as many countries and regions and spotlight women of childbearing age. Researchers from IPEN coordinated hair sampling from 1044 women of reproductive age in 37 locations across 25 countries on 6 continents. Analysis, conducted by BRI, found that 42% of women sampled had average mercury levels over the US EPA health advisory level of 1ppm, above which brain damage, IQ loss, and kidney and cardiovascular damage may occur.
The study additionally found that 53% of the global sample of women measured more than 0.58ppm of mercury, a level associated with the onset of fetal neurological damage.
(2017) A new study, supported by the Minamata Convention’s Interim Secretariat hosted by UN Environment, reveals that women of childbearing age living in four Pacific Island countries have elevated levels of mercury in their bodies. Mercury monitoring in women of childbearing age in the Asia and the Pacific Region, jointly conducted by the interim secretariat of the Minamata Convention, Biodiversity Research Institute (BRI), and IPEN, examined hair samples from women aged 18 - 44 from Cook Islands, Marshall Islands, Tuvalu, and Kiribati, and two landlocked Asian countries, Tajikistan and Nepal.
In 2015, IPEN collabroated with Arnika and BRI to create a poster highlighting the countries where sampling was carried out, the organizations that gathered the media for sampling, major findings and more.
In 2011, IPEN partnered with the Biodiversity Research Institute to undertake a Global Fish and Community Mercury Monitoring Project. The goal of this project is to generate new data and raise awareness about global mercury pollution and specific hot spots, primarily from developing and transition countries. Mercury monitoring information generated through the project to date includes sampling results from both fish/seafood and biomonitoring (via hair sampling).
A January 2013 report, Global Mercury Hotspots, revealed that mercury contamination regularly exceeds health advisory levels in humans and fish worldwide. The report was the first of its kind to identify ten global biological mercury hotspots of particular concern to human populations and the ecosystems on which they depend. The report was updated in September, 2013 in preparation for the Mercury Treaty Diplomatic Conference held in Japan in October, 2013.
NEWS: IPEN Participating Organization Volgograd-Ecopress was taken to court in 2014 by the chlor alkali industry in Russia, who claimed that mercury testing results revealed in the report were false.
This map shows the geographic scope of the mercury montoring project.
In 2010, IPEN partnered with the Swedish Society for Nature Conservation to test hair samples for mercury from government delegates and other participants at the 1st international negotiating committee meeting for a treaty on mercury. More than one-third of the samples exceeded the US National Research Council mercury reference dose of 1000 ug/kg. | https://ipen.org/projects/mercury-fish-and-human-hair |
Never before have we experienced social isolation on a massive scale as we have during the evolving COVID-19 pandemic. A new paper published in the journal Trends in Cognitive Sciences explores the wide-ranging, negative consequences that social isolation has on our psychological well-being and physical health, including decreased life span. The paper was co-authored by Associate Professor Danilo Bzdok (McGill University and Mila Quebec Artificial Intelligence Institute) and Emeritus Professor Robin Dunbar (University of Oxford).
Through examining a broad range of studies, a full picture emerged of the severe impact that loneliness can have:
- having strong interpersonal relationships is critical for survival across the entire lifespan;
- social isolation is a significant predictor of the risk of death;
- insufficient social stimulation affects reasoning and memory performances, hormone homeostasis, brain grey/white-matter, connectivity and function, as well as resilience to physical and mental disease;
- feelings of loneliness can spread through a social network, causing negatively skewed social perception, escalating morbidity and mortality, and, in older people, precipitating the onset of dementia such as Alzheimer’s disease.
Loneliness directly impairs the immune system, making us less resistant to diseases and infections. Indeed, feeling lonely and having few friends can result in a particularly poor immune defence. People who are more socially integrated, however, have better adjusted biomarkers for physiological function, including lower systolic blood pressure, lower body mass index, and lower levels of C-reactive protein (another molecular response to inflammation).
Humans are intensely social and benefit psychologically and physically from social interaction. The tighter we are embedded in a network of friends, for example, the less likely we are to become ill and the higher our rates of survival. People who belong to more groups, such as sports clubs, church, hobby groups, have been found to reduce their risk of future depression by almost 25%.
Associate Professor Department of Biomedical Engineering at McGill University & Canada CIFAR Artificial Intelligence Chair Danilo Bzdok, said: “We are social creatures. Social interplay and cooperation have fuelled the rapid ascent of human culture and civilization. Yet, social species struggle when forced to live in isolation. From babies to the elderly, psychosocial embedding in interpersonal relationships is critical for survival. It is now more urgent than ever to narrow the knowledge gap of how social isolation impacts the human brain as well as mental and physical well-being.”
Emeritus Professor of Evolutionary Psychology Robin Dunbar, said: “Loneliness has accelerated in the past decade. Given the potentially severe consequences this can have on our mental and physical health, there is growing recognition and political will to confront this evolving societal challenge. As one consequence, the United Kingdom has launched the ‘Campaign to End Loneliness’ – a network of over 600 national, regional and local organizations to create the right conditions for reducing loneliness in later life. Such efforts speak to the growing public recognition and political will to confront this evolving societal challenge. These concerns can only be exacerbated if there are prolonged periods of social isolation imposed by national policy responses to extraordinary crises such as COVID-19.”
About the study
“The Neurobiology of Social Distance” was published in Trends in Cognitive Sciences.
DOI: https://doi.org/10.1016/j.tics.2020.05.016
About McGill University
Founded in Montreal, Quebec, in 1821, McGill University is Canada’s top ranked medical doctoral university. McGill is consistently ranked as one of the top universities, both nationally and internationally. It is a world-renowned institution of higher learning with research activities spanning two campuses, 11 faculties, 13 professional schools, 300 programs of study and over 40,000 students, including more than 10,200 graduate students. McGill attracts students from over 150 countries around the world, its 12,800 international students making up 31% of the student body. Over half of McGill students claim a first language other than English, including approximately 19% of our students who say French is their mother tongue. | https://www.mcgill.ca/newsroom/channels/news/neurobiology-social-distance-322652 |
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Author
Amery, Heather.
Title
First thousand words in French / by Heather Amery and Katherine Folliot ; illustrated by Stephen Cartwright.
Imprint
New York : Mayflower Books,
Copies
Location
Call No.
OPAC Message
Status
Nettels Non-Fiction
443 Amery
---
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Nettels Non-Fiction
443 Amery
---
Available
Edition
1st edition.
Description
63 p. : colored illustrations ; 28 cm.
Note
Cataloging based on CIP information.
Text in French.
Summary
Presents 1,000 common French words accompanied by drawings. Contains a pronunciation guide.
Subject
French language -- Vocabulary -- Juvenile literature.
French language -- Vocabulary.
Added Author
Folliot, Katherine.
Cartwright, Stephen, 1947-2004 illustrator. | http://kids-sierra.pittstate.edu/search~S1?/dVocabulary+--+Juvenile+films./dvocabulary+juvenile+films/-53%2C1%2C1%2CB/frameset&FF=dvocabulary+french+language+juvenile+literature&1%2C1%2C |
Title IV of the ADA amended the landmark Communications Act of 1934 primarily by adding section 47 U.S.C. § 225. This section requires that all telecommunications companies in the U.S. take steps to ensure functionally equivalent services for consumers with disabilities, notably those who are deaf or hard of hearing and those with speech impairments. When Title IV took effect in the early 1990s, it led to the installation of public teletypewriter (TTY) machines and other TDD (telecommunications devices for the deaf). Title IV also led to the creation, in all 50 states and the District of Columbia, of what was then called dual-party relay services and now are known as Telecommunications Relay Services (TRS), such as STS relay. Today, many TRS-mediated calls are made over the Internet by consumers who use broadband connections. Some are Video Relay Service (VRS) calls, while others are text calls. In either variation, communication assistants translate between the signed or typed words of a consumer and the spoken words of others. In 2006, according to the Federal Communications Commission (FCC), VRS calls averaged two million minutes a month.
Because they only read text, screen readers and refreshable Braille displays cannot interpret photographs, charts, color-coded information, or other graphic elements on a webpage. For this reason, a photograph of a mayor on a city’s website is inaccessible to people who use these assistive technologies, and a blind person visiting the website would be unable to tell if the image is a photo, a logo, a map, a chart, artwork, a link to another page, or even a blank page.
That’s good news if you are one of the many Americans who have a visual, hearing, or mobility disability that makes it difficult to access some information on the web. If you are a business owner who hasn’t made provisions to ensure that your website and other online assets are ADA compliant, you could be looking at a host of legal and financial penalties.
Reasonable accommodation is any change or adjustment to a job or work environment that permits a qualified applicant or employee with a disability to participate in the job application process, to perform the essential functions of a job, or to enjoy benefits and privileges of employment equal to those enjoyed by employees without disabilities. For example, reasonable accommodation may include:
This title requires telephone and Internet companies to provide a nationwide system of interstate and intrastate telecommunications relay services that allows individuals with hearing and speech disabilities to communicate over the telephone. This title also requires closed captioning of federally funded public service announcements. This title is regulated by the Federal Communication Commission.
When collecting feedback, ask users what type of adaptive technologies they use. This will allow you to cater your website to your particular clientele, and will help you appoint resources toward the best compliance options. Navigating the Internet is particularly challenging for people with limited or no vision. Many blind people use specialized web browsers and software that works with standard web browsers, like Internet Explorer, that have features that enable users to maximize their Internet use and experience. This screen reading software reads the HTML code for websites, and gives the user a verbal translation of what is on screen.
The attorneys' fees provision of Title III does provide incentive for lawyers to specialize and engage in serial ADA litigation, but a disabled plaintiff does not obtain financial reward from attorneys' fees unless they act as their own attorney, or as mentioned above, a disabled plaintiff resides in a state that provides for minimum compensation and court fees in lawsuits. Moreover, there may be a benefit to these "private attorneys general" who identify and compel the correction of illegal conditions: they may increase the number of public accommodations accessible to persons with disabilities. "Civil rights law depends heavily on private enforcement. Moreover, the inclusion of penalties and damages is the driving force that facilitates voluntary compliance with the ADA." Courts have noted:
Shortly before the act was passed, disability rights activists with physical disabilities coalesced in front of the Capitol Building, shed their crutches, wheelchairs, powerchairs and other assistive devices, and immediately proceeded to crawl and pull their bodies up all 100 of the Capitol's front steps, without warning. As the activists did so, many of them chanted "ADA now", and "Vote, Now". Some activists who remained at the bottom of the steps held signs and yelled words of encouragement at the "Capitol Crawlers". Jennifer Keelan, a second grader with cerebral palsy, was videotaped as she pulled herself up the steps, using mostly her hands and arms, saying "I'll take all night if I have to." This direct action is reported to have "inconvenienced" several senators and to have pushed them to approve the act. While there are those who do not attribute much overall importance to this action, the "Capitol Crawl" of 1990 is seen by some present-day disability activists in the United States as a central act for encouraging the ADA into law.
The next factor is language. Although web design doesn’t require someone who speaks the same language, it’s important that your designer understands your requirements. This can be more difficult if you don’t speak the same language fluently. You can interview a freelancer to explain your requirements and get a feel for their understanding of the project before you begin.
Because web designers tend to work as freelancers on a project basis, they must be excellent communicators, willing to manage their own work, and available on your schedule. Some critical skills, such as working collaboratively and responding enthusiastically to feedback, aren’t core to good web design, but make working with a web designer much easier. Finally, look for a web designer who has cross-functional knowledge, such as understanding marketing and conversion rate optimization in addition to web design.
Because the ADA establishes overlapping responsibilities in both EEOC and DOJ for employment by State and local governments, the Federal enforcement effort is coordinated by EEOC and DOJ to avoid duplication in investigative and enforcement activities. In addition, since some private and governmental employers are already covered by nondiscrimination and affirmative action requirements under the Rehabilitation Act of 1973, EEOC, DOJ, and the Department of Labor similarly coordinate the enforcement effort under the ADA and the Rehabilitation Act.
In the context of employment, the ADA prohibits employers from taking disability into consideration in all aspects of the employment relationship—from hiring to firing and virtually everything in between. The law also requires employers to make reasonable accommodations for individuals with disabilities to help them do their job. Outside of employment, the ADA requires most public places, such as shops, restaurants, and movie theaters, to be accessible to those with disabilities. State and local laws can also provide further protections.
Thanks for writing. While I’m not a lawyer I believe if your physical practice is ADA exempt your web presence, as an extension of that physical business would maintain the same exemption status. If you’d like to be absolutely certain I’d confer with an ADA lawyer (email us, questions at yokoco dot com if you need a referral) but I don’t believe you have reason to worry.
The ADA is the Americans with Disabilities Act, passed almost 30 years ago in 1990. This act was originally put in motion pertaining solely to physical location. It requires establishments to provide people with disabilities easy access to various levels throughout the business. This act was set to achieve an equal experience to all people, handicapped or not.
Technology is changing, and many website designers are using creative and innovative ways to present web-based materials. These changes may involve new and different access problems and solutions for people with disabilities. This Chapter discusses just a few of the most common ways in which websites can pose barriers to access for people with disabilities. By using the resources listed at the end of this Chapter, you can learn to identify and address other barriers.
Level AA is a little more significant, and makes sites accessible to people with a wider range of disabilities, including the most common barriers to use. It won't impact the look and feel of the site as much as Level AAA compliance, though it does include guidance on color contrast and error identification. Most businesses should be aiming for Level AA conformity, and it appears to reflect the level of accessibility the DOJ expects.
The Department of Justice (DOJ) has specifically stated in rulings that websites should be designed so they are accessible to individuals who have vision, hearing, and physical disabilities. There’s a growing body of case law where the DOJ required companies to provide an ADA compliant website and levied hefty penalties when sites failed to measure up. | https://garvetechnologies.com/hire-ada-website-designer10/ada-compliance-number-of-employees-florida-ada-compliance.html |
About F5 Networks:
F5 Networks, Inc. is a global company that specializes in application services and application delivery networking (ADN). F5 technologies focus on the delivery, security, performance, and availability of web applications, as well as the availability of servers, cloud resources, data storage devices, and other networking components. F5 is headquartered in Seattle, Washington, with additional development, manufacturing, and sales/marketing offices worldwide.
Company Name: F5 Networks
Website: www.f5.com
Designation: Software Engineer- I
Job Location: Bangalore
Experience: 0-1 Years
Salary: INR 9LPA-INR 13.00 LPA
Eligibility:
- BE/B.Tech
- ME/MTech
- CSE/ECE/IT/EEE/Computers 2019 Passed out.
- Percentage 80% and above throughout academics..
Skills Criteria:
- Strong analytic / trouble-shooting skills.
- Good knowledge on C/C++/Java
- Good software designing skills, with object-oriented concepts.
- Good knowledge in Linux user space programing, linux IPC, RPC, multi threading features.
- Able to collaborate and thrive in a fast-paced high-performance environment.
- Demonstrated excellence in written and verbal communications
- Minimum two years product development experience in networking domain (TCP/IP, Routing, switching, and Linux networking stack).
Good to Have Skills:
- Knowledge of docker containers, kubernetes
- REST based web services development and micro services
- Automation systems like Ansible, Chef, or Puppet
- Agile based software development methodologies like SCRUM.
Job Position:
- Responsible for the design and development of features and components in the application/protocol areas as well as the automation necessary to test and deploy new features.
- You will work with architects, leads, Product Management, cross-functional teams, and other stakeholders to implement solutions.
Note:
- This is not direct walk-in shortlisted candidates will receive call regarding the schedule.
- Candidate should be available for F2F discussion on 20th May.
- Female Candidates only required to apply for the drive. | http://expertjobs.org/f5-networks-off-campus-drive-2019-software-engineer-salary-inr-13-00-lpa-2/ |
Introduction {#cti21001-sec-0001}
============
Crohn\'s disease (CD) and ulcerative colitis (UC), collectively termed Inflammatory Bowel Disease (IBD), are some of the most extensively and successfully studied diseases in complex disease genetics. However, genetic studies in CD were not always successful. Initial efforts to identify the genetic determinants of CD were performed using linkage mapping and were largely disappointing, often producing weak or inconsistent signals.[1](#cti21001-bib-0001){ref-type="ref"} One exception to this was the discovery of *NOD2* as a major CD susceptibility gene[2](#cti21001-bib-0002){ref-type="ref"}, [3](#cti21001-bib-0003){ref-type="ref"}, [4](#cti21001-bib-0004){ref-type="ref"} -- a finding that represents one of the few successes of linkage mapping across all diseases. The development of genome‐wide association studies (GWAS), which facilitate a hypothesis‐free comparison of allele frequencies at thousands of single nucleotide polymorphisms (SNPs) between cases and controls (Figure [1](#cti21001-fig-0001){ref-type="fig"}), transformed the study of CD genetics and led to the discovery of many CD susceptibility SNPs. Nonetheless, the overall number of hits identified in early, single cohort GWAS studies was typically modest (between 1 and 10) due to relatively small sample sizes and the resulting limitations in study power.[5](#cti21001-bib-0005){ref-type="ref"}, [6](#cti21001-bib-0006){ref-type="ref"}, [7](#cti21001-bib-0007){ref-type="ref"}, [8](#cti21001-bib-0008){ref-type="ref"} Fortunately, the combination of a high disease heritability and a strong collaborative spirit between research groups from around the world meant that subsequent meta‐analyses could include much larger numbers of samples and were accordingly far more successful in identifying the genetic determinants of IBD.[9](#cti21001-bib-0009){ref-type="ref"}, [10](#cti21001-bib-0010){ref-type="ref"}, [11](#cti21001-bib-0011){ref-type="ref"}, [12](#cti21001-bib-0012){ref-type="ref"} For example, in 2008, the first international meta‐analysis was performed by combining GWAS data from the UK, US and Franco‐Belgian IBD Genetics consortia[13](#cti21001-bib-0013){ref-type="ref"} -- studies that had individually identified a total of 10 susceptibility loci.[5](#cti21001-bib-0005){ref-type="ref"}, [6](#cti21001-bib-0006){ref-type="ref"}, [8](#cti21001-bib-0008){ref-type="ref"} The gain in power that was afforded by combining these data sets led to the identification of 32 associated loci[13](#cti21001-bib-0013){ref-type="ref"} and highlighted the value of collaborating to create larger data sets for analysis. This study was unsurprisingly followed 2 years later by an even larger meta‐analysis -- incorporating \~22 000 cases and \~29 000 controls from 13 different countries -- in which 71 susceptibility loci were identified.[9](#cti21001-bib-0009){ref-type="ref"} Subsequent larger studies, which have taken advantage of more affordable genotyping approaches (such as the Illumina Immunochip), have increased this number even further, with 241 IBD susceptibility loci being confirmed in the most recent analysis.[14](#cti21001-bib-0014){ref-type="ref"} Such advances clearly demonstrate the power of GWAS to provide novel insights into disease pathogenesis, particularly when applied to an ever‐increasing sample size.[15](#cti21001-bib-0015){ref-type="ref"} Interestingly, the majority of these loci increase the risk of both CD and UC,[14](#cti21001-bib-0014){ref-type="ref"} and many of them alter susceptibility to other immune‐mediated diseases as well -- including diseases that are known to be related to IBD, such as primary sclerosing cholangitis, psoriasis and ankylosing spondylitis, and others that were previously thought to be unrelated, such as type 1 diabetes and multiple sclerosis.[16](#cti21001-bib-0016){ref-type="ref"} Despite this undoubted success, however, it is important to note that most GWAS hits are only proxies for the true causal variant(s) at each locus (with which they are inherited through linkage disequilibrium). Indeed, it was the realisation that entire haplotypes could be interrogated by genotyping just one of their constituent SNPs that helped make GWAS possible in the first place, as it meant that genome‐wide genetic variation could be captured using a tractable number of variants (that could be incorporated into a single genotyping chip) (Figure [1](#cti21001-fig-0001){ref-type="fig"}). As such, to identify the functional consequences of these associated haplotypes -- and the mechanism by which they alter disease risk -- it will be important to identify the causal variant(s) that is ultimately responsible for the association. In some cases, this may be possible using statistical fine mapping -- such as has recently been performed by the International Inflammatory Bowel Disease Genetic Consortium (IIBDGC)[17](#cti21001-bib-0017){ref-type="ref"} -- but in others, some form of functional characterisation of the downstream effects of each SNP in a locus will be necessary.
{#cti21001-fig-0001}
Genetics alone will not provide all of the answers, but if combined with careful study of the downstream biology, it seems likely that new pathways involved in disease biology will be discovered -- improving our understanding of disease pathogenesis and potentially providing new opportunities for therapeutic intervention.
Unravelling disease pathogenesis -- the genetic contribution {#cti21001-sec-0002}
============================================================
Although the pathophysiology of CD is not fully understood, the current hypothesis assumes a complex interplay between environmental, genetic and intestinal microbial factors, all of which interact with the host\'s immune system to result in a pathological auto‐inflammatory response directed towards the intestine.[18](#cti21001-bib-0018){ref-type="ref"} During the past decade, GWASs have identified multiple SNPs that -- by virtue of their proximity to genes known to be involved in specific pathways -- have led to the implication of these pathways in disease development. Some of these proposed pathophysiological mechanisms will now be discussed in more detail -- especially those that have made important contributions to our current understanding of CD pathogenesis (Table [1](#cti21001-tbl-0001){ref-type="table-wrap"}).
######
Summary of IBD GWAS hits involved in autophagy, the IL‐17/IL‐23 axis/type 3 innate lymphoid cells and the failure to suppress of aberrant immune responses
Chromosome SNP *P* value OR AF Candidate gene in/near locus
----------------------------------------------- ------------ ------------ ----------- ------- --------------------------- ------------------------------
Autophagy 2 rs6752107 1.42E−73 1.25 0.55 *ATG16L1*
5 rs11741861 2.94E−37 1.25 0.05 *IRGM*
12 rs11564258 6.38E−29 1.33 0.025 *LRRK2*
16 rs2066844 2.27E−217 2.00 0.06 *NOD2*
IL‐23/IL‐17 Axis Type 3 innate lymphoid cells 1 rs11581607 8.76E−175 0.46 0.05 *IL23R*,*IL12RB2*
1 rs4845604 1.21E−17 0.88 0.13 *RORC*
5 rs56167332 7.17E−50 1.17 0.35 *IL12B*
6 rs1819333 6.76E−21 1.08 0.48 *CCR6*
9 rs75900472 4.70E−48 1.16 0.13 *JAK2*
12 rs11614178 2.22E−32 1.19 0.4 *IL22*,*IFNG*
17 rs12942547 5.51E−22 1.1 0.55 *STAT3*,*STAT5A*,*STAT5B*
19 rs11879191 5.27E−20 0.89 0.2 *TYK2*
21 rs7282490 2.35E−26 1.1 0.39 *ICOSLG*
Failure to suppress aberrant immune responses 1 rs3024505 2.99E−50 1.22 0.19 *IL10*
4 rs7657746 3.00E−13 1.1 0.20 *IL2*
7 rs1077773 5.96E−9 0.93 0.48 *AHR*
10 rs12722515 3.76E−10 1.1 0.85 *IL2RA*
15 rs17293632 2.71E−20 1.11 0.14 *SMAD3*
16 rs529866 1.73E−16 1.12 0.81 *SOCS1*
17 rs12942547 5.51E−22 1.1 0.55 *STAT3*,*STAT5A*,*STAT5B*
18 rs7240004 1.01E−10 0.94 0.34 *SMAD7*
21 rs2284553 2.14E−16 1.12 0.60 *IL10RB*
Data are collated from Jostins *et al*.,[11](#cti21001-bib-0011){ref-type="ref"} Liu *et al*.,[12](#cti21001-bib-0012){ref-type="ref"} and Huang *et al*.[17](#cti21001-bib-0017){ref-type="ref"}
Allele frequency (AF) refers to allele frequency in 1000 genomes CEU population of the allele for which odds ratio (OR) is reported.
John Wiley & Sons, Ltd
Autophagy {#cti21001-sec-0003}
---------
Prior to genetic studies that identified *ATG16L1* and *IRGM* as susceptibility loci for CD,[7](#cti21001-bib-0007){ref-type="ref"}, [19](#cti21001-bib-0019){ref-type="ref"} a role for autophagy in disease pathogenesis had not been envisaged. Autophagy is a well‐described and evolutionarily conserved process whereby cytoplasmic components are engulfed by double‐membraned vesicles (autophagosomes) that then fuse with lysozymes in order for their contents (protein aggregates and damaged organelles) to be degraded and recycled.[20](#cti21001-bib-0020){ref-type="ref"} Given the importance of intestinal microbes in CD pathogenesis, it is notable that autophagy also plays a role in clearance of intracellular micro‐organisms (a process known as 'xenophagy').[21](#cti21001-bib-0021){ref-type="ref"}, [22](#cti21001-bib-0022){ref-type="ref"} Moreover, autophagy has also been linked to endoplasmic reticulum (ER) stress[23](#cti21001-bib-0023){ref-type="ref"} -- another process that has been implicated in intestinal inflammation and IBD.[24](#cti21001-bib-0024){ref-type="ref"} ER stress has been shown to induce autophagy, and autophagy reciprocally plays a role in resolving ER stress.[25](#cti21001-bib-0025){ref-type="ref"} Interestingly, Crohn\'s disease risk SNPs seem to be able to disrupt this balance, which can lead to intestinal inflammation.[26](#cti21001-bib-0026){ref-type="ref"}
When autophagy genes were first associated with CD, the mechanism by which autophagy altered disease risk was unknown. Several groups therefore sought to investigate this by genetically targeting *ATG16L1* [27](#cti21001-bib-0027){ref-type="ref"}, [28](#cti21001-bib-0028){ref-type="ref"}, [29](#cti21001-bib-0029){ref-type="ref"} -- the first autophagy gene to be identified.[7](#cti21001-bib-0007){ref-type="ref"} Most of these studies used loss‐of‐function approaches (i.e. *ATG16L1* knockout or knock‐down) and while they provided interesting insights into the role of autophagy in intestinal inflammation, it was unclear as to how the results might relate to the risk variant identified by GWAS. This was because unlike most GWAS hits, which are typically noncoding and thus presumed to affect gene expression, the risk SNP in *ATG16L1* is a missense mutation that leads to a threonine to alanine substitution at position 300 (rs2241880, Thr300Ala or T300A).[7](#cti21001-bib-0007){ref-type="ref"} Missense mutations are generally assumed to affect protein structure or function due to the effect that an amino acid substitution could have on protein folding -- but would not be expected to directly affect the amount of the protein, as are typically modelled with loss‐of‐function approaches. However, in this case, it was subsequently shown that the missense mutation does primarily affect the amount of ATG16L1 protein within cells, rather than the function of the protein *per se*, as the alanine substitution makes ATG16L1 protein more susceptible to caspase‐3‐mediated degradation.[30](#cti21001-bib-0030){ref-type="ref"} This in turn reduces ATG16L1 levels, and hence autophagy, during periods of cellular stress (e.g. inflammation) and results in defective clearance of intracellular pathogens and increased inflammatory cytokine production.[30](#cti21001-bib-0030){ref-type="ref"} A similar effect on intracellular pathogen clearance was also reported at the *IRGM* locus. Here, the original GWAS association (rs1000113 C\>T) was shown to be in perfect linkage disequilibrium with a synonymous exonic SNP (rs10065172 C\>T) that is located within a binding site ('seed sequence') for a microRNA, miR‐196. This microRNA was found to be highly expressed within the intestinal epithelia of patients with CD, and its expression was shown to anti‐correlate with *IRGM* mRNA levels -- consistent with a physiological role in repressing IRGM.[31](#cti21001-bib-0031){ref-type="ref"} Interestingly, the disease‐associated variant (T) at rs10065172 disrupted the miR‐196 seed sequence, so that miR‐196 could not bind and resulted in carriers of the CD‐associated variant being unable to repress *IRGM* mRNA levels, which led to impaired autophagy and a failure to clear intracellular bacteria.[31](#cti21001-bib-0031){ref-type="ref"} These examples, where the functional consequences of a risk allele have been elucidated, are relatively uncommon, but highlight how the study of genetic variants can uncover specific pathway defects that contribute to CD pathogenesis.
In addition to helping resolve the role of autophagy in CD pathogenesis, the identification of genetic risk variants in known autophagy genes also led to the realisation that other susceptibility genes, which had not previously been linked to autophagy, might actually be involved in this process. For example, *NOD2 --* the first CD susceptibility gene to be discovered[2](#cti21001-bib-0002){ref-type="ref"}, [3](#cti21001-bib-0003){ref-type="ref"}, [4](#cti21001-bib-0004){ref-type="ref"} -- was principally thought to be an intracellular pattern recognition receptor involved in defence against bacteria,[32](#cti21001-bib-0032){ref-type="ref"} but it was subsequently shown that NOD2 also interacts with ATG16L1 during autophagosome formation.[33](#cti21001-bib-0033){ref-type="ref"}, [34](#cti21001-bib-0034){ref-type="ref"}, [35](#cti21001-bib-0035){ref-type="ref"}
The identification of autophagy genes, and specifically *ATG16L1*, also helped uncover the important role that Paneth cells are thought to play in Crohn\'s disease. Paneth cells are located at the base of intestinal crypts and are known to be involved in mucosal defence, producing large amounts of anti‐microbial peptides, including defensins.[36](#cti21001-bib-0036){ref-type="ref"} Early studies into the role of autophagy in intestinal inflammation revealed that mice with reduced *Atg16l1* expression had morphologically abnormal Paneth cells with reductions in the number and size of secretory granules.[37](#cti21001-bib-0037){ref-type="ref"} Similar defects were also noted in CD patients who were homozygous for the *ATG16L1* T300A variant.[38](#cti21001-bib-0038){ref-type="ref"} Interestingly, Paneth cell dysfunction has also been reported in mice following deletion of a transcription factor (*Xbp1*), which is involved in the unfolded protein response (UPR) and thereby helps to resolve ER stress.[24](#cti21001-bib-0024){ref-type="ref"} Indeed, it was subsequently shown that CD‐like ileitis spontaneously develops in mice if the UPR and autophagy were simultaneously compromised in Paneth cells, suggesting that the balance between ER stress and autophagy is likely to set an important threshold for initiating intestinal inflammation.[39](#cti21001-bib-0039){ref-type="ref"}
The realisation that autophagy plays an important role in CD has also led to questions about whether pharmacological manipulation of autophagy could be used therapeutically. Studies involving mouse models have shown that rapamycin (sirolimus), which upregulates autophagy by inhibiting mTOR, can ameliorate experimental colitis.[40](#cti21001-bib-0040){ref-type="ref"}, [41](#cti21001-bib-0041){ref-type="ref"} A beneficial effect of sirolimus has also been reported in a case study of an adult with refractory CD[42](#cti21001-bib-0042){ref-type="ref"} and a retrospective case series of children with refractory IBD,[43](#cti21001-bib-0043){ref-type="ref"} although no randomised placebo‐controlled trials have yet been performed. This, however, remains an active area of research, not least because sirolimus is also known to also have anti‐fibrotic effects that could be beneficial in CD -- a trial investigating this is currently underway (NCT02675153).
The IL‐23/IL‐17 axis, bridging the innate and adaptive immune system {#cti21001-sec-0004}
--------------------------------------------------------------------
Early studies into the pathogenesis of IBD identified differences in the ratio of T helper (T~H~)1/T~H~2 cells in the intestinal mucosa of patients with CD or UC, and corresponding differences in their cytokine profiles.[44](#cti21001-bib-0044){ref-type="ref"}, [45](#cti21001-bib-0045){ref-type="ref"}, [46](#cti21001-bib-0046){ref-type="ref"} CD appeared to be a T~H~1‐associated disease with increased levels of interferon‐γ and IL‐12, while UC appeared to more T~H~2‐like -- being characterised by increased IL‐5 and IL‐13 production (although not IL‐4). Several animal models supported this hypothesis, with an anti‐IL‐4 antibody showing therapeutic benefit in oxazolone‐induced colitis,[47](#cti21001-bib-0047){ref-type="ref"} which histologically resembles UC, while the transmural, CD‐like colitis induced by 2,4,6 trinitrobenzene sulphonic acid could be abrogated by an anti‐IL‐12 antibody[48](#cti21001-bib-0048){ref-type="ref"} -- a molecule that was subsequently found to be effective in human CD trials.[49](#cti21001-bib-0049){ref-type="ref"} However, this hypothesis ultimately proved to be overly simplistic, and it was soon realised that the anti‐IL‐12 antibody would have also blocked IL‐23 due to its target antigen being a common subunit (p40) that is shared between these cytokines.[50](#cti21001-bib-0050){ref-type="ref"} Indeed, it was later shown that the effect upon IL‐23, a cytokine important in the development and maintenance of mucosal effector T~H~17 cells, was responsible for the therapeutic benefit in animal models.[51](#cti21001-bib-0051){ref-type="ref"} Activated T~H~17 cells could also be identified in the blood and intestine of CD patients.[52](#cti21001-bib-0052){ref-type="ref"} Around this time, genetics provided further support for a possible role of T~H~17 cells in CD and UC, with numerous susceptibility variants being identified within or near to genes implicated in T~H~17 biology (e.g. *RORC*,*IL23R*,*IL12B*,*TYK2*,*JAK2*,*STAT3*,*CCR6* and *ICOSLG*, Table [1](#cti21001-tbl-0001){ref-type="table-wrap"}).[9](#cti21001-bib-0009){ref-type="ref"}, [10](#cti21001-bib-0010){ref-type="ref"} However, while these genetic associations are consistent with a role for T~H~17 cells in CD pathogenesis, it is important to note that the functional consequences of the risk alleles at most of these loci have not yet been elucidated. As such, we still need to confirm that these genes are directly affected by the disease‐associated SNPs at these loci, and also that the functional consequences of the risk alleles specifically affect IL‐23/IL‐17 signalling, as several of these genes are also involved in other pathways (e.g. *STAT3* is critical for IL‐10 signalling). Accordingly, the precise role of T~H~17 cells in CD pathogenesis still needs to be fully characterised, and in this context, it is notable that antibodies which target a key T~H~17 cytokine, IL‐17, are ineffective in CD[53](#cti21001-bib-0053){ref-type="ref"} and yet are highly effective in other T~H~17‐driven diseases.[54](#cti21001-bib-0054){ref-type="ref"}
Another reason why the exact role of T~H~17 cells remains obscure, despite several lines of evidence appearing to implicate them in CD pathogenesis, is because of the discovery of innate lymphoid cells (ILCs). These cells belong to the lymphoid lineage but do not express antigen‐specific receptors and are therefore not part of the adaptive immune system.[55](#cti21001-bib-0055){ref-type="ref"} Nonetheless, subsets of ILCs exist that mirror T‐cell subsets in terms of their cytokine secretion profiles.[55](#cti21001-bib-0055){ref-type="ref"} Type 3 ILC cells (ILC3s), for example, correspond to T~H~17 cells in that they can express RORγt, produce IL‐17 and IL‐22, and are responsive to IL‐23.[55](#cti21001-bib-0055){ref-type="ref"} Moreover, these cells have been shown to be responsible for bacteria‐driven colitis in mice that lack T cells[56](#cti21001-bib-0056){ref-type="ref"} and to selectively accumulate in the intestine of patients with active CD.[57](#cti21001-bib-0057){ref-type="ref"} Nevertheless, their specific contribution to CD pathogenesis -- as distinct from that of T~H~17 cells -- is difficult to ascertain because not only are they greatly outnumbered by T cells in the intestine, but many of the methods used to deplete them will also affect T cells (and vice versa) making it difficult to disentangle their relative contributions. To complicate things further, it appears that other ILC subsets may also play a role in CD pathogenesis. For example, type 1 ILCs (ILC1s), which resemble T~H~1 cells in that they express the transcription factor T‐bet, respond to IL‐12 and can produce interferon‐γ, are substantially increased in the intestine of patients with CD.[58](#cti21001-bib-0058){ref-type="ref"} For this reason, although the exact role of ILCs in IBD pathogenesis has not been fully established, this remains an active area of research -- especially as they might provide tissue‐specific therapeutic targets for some patients.
The failure to suppress aberrant immune responses {#cti21001-sec-0005}
-------------------------------------------------
It has been estimated that the human body contains \~40 trillion bacteria, of which the vast majority are located within the intestine.[59](#cti21001-bib-0059){ref-type="ref"} This means that there are actually more bacteria in our bodies than human cells and illustrates why the intestine presents such a challenge to the immune system. In order to be able to mount an appropriate immune response to intestinal pathogens, for example, there have to also be mechanisms to prevent aberrant responses to nonpathogenic gut commensals in order to preserve health. Disrupting such control mechanisms is known to lead to colitis in animal models -- for example, if the *Il10* gene is deleted[60](#cti21001-bib-0060){ref-type="ref"} or if regulatory T cells are absent.[61](#cti21001-bib-0061){ref-type="ref"} Results from GWAS studies have demonstrated that disruption of these anti‐inflammatory mechanisms is also likely to be involved in the development of CD. For example, several genes involved in IL‐10 signalling (the anti‐inflammatory cytokine which when deleted leads to colitis in animal models) lie near to GWAS hits, including *IL10*,*IL10RB*,*STAT3* and *TYK2*.[11](#cti21001-bib-0011){ref-type="ref"}, [62](#cti21001-bib-0062){ref-type="ref"} Although the functional consequences of these SNPs have not been determined, the notion that IL‐10 signalling may be defective in IBD is supported by other genetic studies. For example, private missense mutations in genes encoding components of the IL‐10 receptor (*IL10RA* or *IL10RB*) have also been shown to cause a severe, early‐onset form of IBD in consanguineous families due to abrogation of IL‐10 signalling.[63](#cti21001-bib-0063){ref-type="ref"} Other anti‐inflammatory cytokines -- and genes involved in their signalling pathways -- have also been identified within CD‐associated genetic loci, including *IL22* (another member of the IL‐10 cytokine family) and *SMAD3* and *SMAD7*, which are important components of TGFβ signalling. Indeed, SMAD7, which inhibits TGFβ signalling and is expressed at high levels in the intestines of patients with IBD,[64](#cti21001-bib-0064){ref-type="ref"} has been shown to be an effective therapeutic target via an antisense oligonucleotide (Mongersen) that binds to and degrades *SMAD7* mRNA.[65](#cti21001-bib-0065){ref-type="ref"}
Although several cell types are known to play a role in suppressing exuberant immune responses, including M‐2 macrophages, certain ILC populations and regulatory B cells, by far the most studied immunosuppressive cell type are regulatory T cells (Tregs). Several GWAS hits also highlight the importance of Tregs in IBD pathogenesis. For example, it is known that IL‐2 signalling is critical for maintaining Treg numbers[66](#cti21001-bib-0066){ref-type="ref"} and for mediating their suppressor function via activation of STAT5,[67](#cti21001-bib-0067){ref-type="ref"} and GWASs have identified IBD‐associated loci that contain *IL2*,*IL2RA* (part of the IL‐2 receptor) and *STAT5*.[11](#cti21001-bib-0011){ref-type="ref"} Moreover, IL‐10 signalling -- discussed earlier -- is also important in conferring Tregs with the ability to suppress T~H~17‐mediated inflammation[68](#cti21001-bib-0068){ref-type="ref"} and in mediating that suppression.[69](#cti21001-bib-0069){ref-type="ref"} Additionally, there is a growing realisation that plasticity exists within T‐cell subsets and particularly between Tregs and T~H~17 cells, with evidence that T~H~17 cells can transdifferentiate into Tregs as inflammation resolves -- a process that involves signalling through the aryl‐hydrocarbon receptor (*AHR*), which also harbours a genetic association with IBD.[12](#cti21001-bib-0012){ref-type="ref"} Further evidence of the role of Tregs in intestinal inflammation can also be found in patients who carry rare missense mutations in *FOXP3*, which encodes the master transcription factor for naturally occurring Tregs. The resulting syndrome, termed 'immunodysregulation, polyendocrinopathy, enteropathy, X‐linked syndrome' or 'IPEX',[70](#cti21001-bib-0070){ref-type="ref"} is characterised by an autoimmune enteropathy as well as several other severe autoimmune phenomena.
Based on these and other insights, Tregs are now also being studied as potential therapies in IBD. Different strategies have been proposed including inducing Tregs *ex vivo* from naïve T cells using an unrelated antigen[71](#cti21001-bib-0071){ref-type="ref"} or isolating thymically derived Tregs and expanding them before re‐infusing them back into patients.[72](#cti21001-bib-0072){ref-type="ref"} These expanded Tregs have been shown to be able to suppress the activation and proliferation of intestinal T cells from CD patients *in vitro* and to have an epigenetically stable *FOXP3* locus, theoretically limiting the possibility for T~H~17 conversion.[72](#cti21001-bib-0072){ref-type="ref"} However, full clinical trials using these approaches have yet to be performed, and it should be noted that in other disease areas, infused regulatory T cells have not shown the same efficacy as had been observed *in vitro* or in animal models.[73](#cti21001-bib-0073){ref-type="ref"}
Overlap with other immune‐mediated diseases -- shared features of autoimmunity? {#cti21001-sec-0006}
===============================================================================
In addition to highlighting pathways that are likely to be important in the development of CD, GWAS has also provided insights into how the genetic architecture of CD relates to that of other autoimmune diseases.[16](#cti21001-bib-0016){ref-type="ref"} For example, while most IBD susceptibility loci are shared between CD and UC, it is notable that SNPs that are implicated in autophagy seem to be specific to CD, while SNPs that are located in, or near to, genes involved in epithelial barrier function tend to be more UC specific.[74](#cti21001-bib-0074){ref-type="ref"} Interesting overlaps have also been noted in other nonintestinal diseases. This is perhaps best exemplified by the IL‐23/IL‐17 axis, to which multiple autoimmune diseases have been linked, including psoriasis (SNPs in or near to *IL23R*,*IL12B*,*TYK2* and *STAT3*), ankylosing spondylitis (SNPs in or near to *IL23R*,*IL12B*,*TYK2* and *JAK2*) and multiple sclerosis (SNPs in or near to *IL12B*,*IL12A*,*TYK2* and *STAT3*). Overlap with some of these diseases, such as psoriasis or ankylosing spondylitis, was unsurprising since these diseases share certain clinical and pathogenic features with CD, although overlap with other diseases, such as multiple sclerosis, was less expected. However, it is important to note that interpreting this overlap is not straightforward. Indeed, just because the same gene is implicated in several diseases does not mean that common genetic haplotypes (and biological mechanisms) are responsible for these associations. For example, although both CD and psoriasis are both associated with multiple SNPs in *TYK2*, these signals are largely distinct.[11](#cti21001-bib-0011){ref-type="ref"}, [75](#cti21001-bib-0075){ref-type="ref"} Indeed, the only shared susceptibility SNP at this locus (rs12720356, a missense variant) shows discordant effects, with the risk allele for CD being protective for psoriasis. Discordant effects at the same SNP are surprisingly common in autoimmune disease genetics and present an additional challenge to understanding how genetic variation can influence disease susceptibility. For example, a SNP in *STAT3*, rs744166, is associated with both CD and multiple sclerosis, but the risk allele for CD is protective for multiple sclerosis and vice versa.[13](#cti21001-bib-0013){ref-type="ref"}, [76](#cti21001-bib-0076){ref-type="ref"} As such, while it is undoubtedly interesting that overlapping associations are detectable across distinct diseases -- either at the SNP or gene level -- much more work needs to be done to determine the true extent of any biological overlap. This work will be particularly important given emerging evidence that drugs targeting these 'shared' pathways may have very different effects between diseases, such as the anti‐IL17 antibody secukinumab, which is highly effective in psoriasis but entirely ineffective in CD.[53](#cti21001-bib-0053){ref-type="ref"}, [54](#cti21001-bib-0054){ref-type="ref"}
More work to do {#cti21001-sec-0007}
===============
Despite the successes described above, much more work needs to be done to fulfil the original goal of GWAS in Crohn\'s disease -- to learn how genetic variation contributes to disease biology. For example, because our ability to identify disease‐associated variants has far outstripped our ability to characterise their functional effects, we still do not know the biological consequences for most of the associated variants. This bottleneck has led to the temptation to assume that we know which gene is mediating the effect at a particular locus -- often because one particular gene might be involved in a familiar aspect of disease biology -- but the reality is that there is often little or no evidence to support this. Indeed, in many cases, we are not even certain of which SNP -- or combination of SNPs -- is responsible for driving the genetic association since the SNPs included on GWAS chips are simply tags for haplotypes that may contain hundreds of associated variants (Figure [1](#cti21001-fig-0001){ref-type="fig"}). Fine‐mapping studies have sought to resolve the genetic associations within GWAS regions, with some success,[11](#cti21001-bib-0011){ref-type="ref"}, [17](#cti21001-bib-0017){ref-type="ref"} although strong linkage disequilibrium has prevented the identification of a single causal variant for most loci.[17](#cti21001-bib-0017){ref-type="ref"} Similarly, there have been several efforts to understand how genetic variation at a locus might affect the expression of nearby genes -- especially since most GWAS hits (and their associated haplotypes) do not appear to affect the coding sequence of genes. This has commonly been done by combining genotypic data with transcriptomic data in order to identify correlations between SNP genotypes and gene expression. However, even when genetic variants are identified that correlate with gene expression (termed expression quantitative trait loci or eQTLs), strong linkage disequilibrium usually means that it is not possible to identify which of the SNPs within the haplotype is responsible for the observed effect.[77](#cti21001-bib-0077){ref-type="ref"}, [78](#cti21001-bib-0078){ref-type="ref"} As such, while these studies can be useful for identifying the genes that are affected by genotype at a particular SNP, they usually cannot identify the causal SNP within the haplotype. Moreover, these studies have revealed that many eQTL effects are only detectable in a specific cell type and/or in the presence of a specific stimulus,[77](#cti21001-bib-0077){ref-type="ref"}, [78](#cti21001-bib-0078){ref-type="ref"} meaning that a causal variant could easily be overlooked if the wrong tissue or condition is being examined.[79](#cti21001-bib-0079){ref-type="ref"}
For these reasons, a major goal of future studies should be to functionally dissect the consequences of disease‐associated genetic variation at each locus in order to avoid incorrectly attributing an association with a gene that is not involved and/or overlooking an important gene that is involved in an unknown aspect of disease biology because it might appear irrelevant. This is no small task, as it will need to include identification of both the cell types in which the effect is relevant and also the context (e.g. during a particular stage in development or in the presence of a particular stimulus). Examples of such studies have been performed in other fields,[80](#cti21001-bib-0080){ref-type="ref"}, [81](#cti21001-bib-0081){ref-type="ref"}, [82](#cti21001-bib-0082){ref-type="ref"} but will need to be embraced by IBD researchers in order to understand the underlying mechanisms and functional consequences of disease‐associated noncoding genetic variation (Figure [2](#cti21001-fig-0002){ref-type="fig"}).
{#cti21001-fig-0002}
Another ongoing challenge in CD genetics is to understand why the genetic variants identified to date account for only a small proportion of the variance of CD (the portion of heritability attributable to genetic variation). It has been estimated that even with such a high number of disease‐associated SNPs, we have only accounted for 26% of CD variance.[83](#cti21001-bib-0083){ref-type="ref"} The remainder, which has been termed 'missing heritability', still has to be accounted for, and there are several hypotheses that might explain this. First, because GWAS studies perform a univariate analysis, they cannot account for gene--gene interactions (epistasis) that might substantially alter the effect size of a given mutation. For example, in psoriasis, an epistatic interaction has been identified between genetic variants in *ERAP1* and *MHC‐C,* which has a much larger effect size that either of the variants in isolation.[84](#cti21001-bib-0084){ref-type="ref"} Second, gene--environment interactions would similarly be expected to alter the effect size attributed to a particular variant if the environmental condition specifically interacted with the pathway affected by a causal SNP. For example, tobacco smoke -- a known environmental risk factor for CD -- has been shown to modify the association between 64 SNPs and CD, including *NOD2* and the HLA region.[85](#cti21001-bib-0085){ref-type="ref"} Third, despite the name, most GWAS chips do not actually provide genome‐wide coverage. As such, it is likely that some of the missing heritability simply lies in regions that have not been analysed to date, either because they are difficult to impute or because they are poorly covered on GWAS chips.[15](#cti21001-bib-0015){ref-type="ref"} For instance, GWAS studies in CD have not yet analysed any SNPs on the sex chromosomes, even though these are likely to contain some disease‐associated variants.[86](#cti21001-bib-0086){ref-type="ref"} Indeed, one of the few studies to include the chromosome‐X was a meta‐analysis of 10 paediatric diseases, including CD and UC, which identified a SNP in *CD40LG*, an X chromosome gene, that was associated with CD, UC and coeliac disease.[87](#cti21001-bib-0087){ref-type="ref"} Similarly, some regions, such as the Fc receptor gene cluster or the *KIR* genes, contain highly repetitive sequences are difficult to genotype using standard approaches. Fourth, it has been proposed that rare variants -- which are not included on GWAS chips but which could have much larger effect sizes -- might account for some of the missing heritability. However, several studies have now been performed to attempt to identify rare disease‐associated variants, but without much success[88](#cti21001-bib-0088){ref-type="ref"}, [89](#cti21001-bib-0089){ref-type="ref"} -- mirroring the situation in other diseases.[90](#cti21001-bib-0090){ref-type="ref"} Fifth, because most GWAS SNPs are proxies for the true causal variant, estimates of variance based on these are likely to underestimate the true attributable risk at each locus. With the introduction of fine‐mapping studies, though, this problem should soon be resolved.
All of these possibilities seek to address the issue of missing heritability from the perspective of identifying missing disease risk. However, it is equally possible that some of the missing heritability might be a consequence of our heritability calculations being incorrect. For instance, estimates of SNP heritability -- the proportion of disease variance accounted for by risk SNPs -- assume that gene--gene interactions do not occur, even though it is widely accepted that they probably do. If heritability calculations are performed using a model that allows epistasis, then it has been shown that up to 80% of the missing heritability in CD can be accounted for.[91](#cti21001-bib-0091){ref-type="ref"} Similarly, if the effects of minor allele frequency (MAF), LD and genotype certainty are factored into calculations of SNP heritability, this also tends to lead to higher estimates.[92](#cti21001-bib-0092){ref-type="ref"}
GWAS in different populations {#cti21001-sec-0008}
=============================
During most of the twentieth century, the incidence of CD rose steadily in the Western world but was relatively low in developing countries.[93](#cti21001-bib-0093){ref-type="ref"} However, recently the incidence of CD in newly industrialised regions has been rising rapidly -- particularly in South East Asia, South America and the Middle East -- such that previously noted ethnic differences appear to be narrowing.[93](#cti21001-bib-0093){ref-type="ref"} This increase in the incidence of CD is also detectable when comparing first‐ and second‐generation immigrants from low risk areas who emigrate to countries with higher incidence of IBD[94](#cti21001-bib-0094){ref-type="ref"} and highlights the importance of environmental factors in CD development. Notably, the vast majority of GWAS studies in IBD have been performed in Caucasian populations (indeed GWAS chips were mostly designed based on Caucasian haplotype structure). Of the few studies that have been performed in individuals of non‐Caucasian descent, the results suggest that there may be some important population‐based differences in the genetic risk of CD. For example, a meta‐analysis of Asian genetic studies revealed that variants in *ATG16L1* and *NOD2*, which are associated with CD in Caucasian populations, were not associated in Han Chinese, Japanese, South Korean, Indian and Malaysian CD populations.[95](#cti21001-bib-0095){ref-type="ref"} Similarly, a GWAS in Ashkenazi Jewish CD patients identified five novel genetic regions not previously found in non‐Jewish Caucasian CD populations.[96](#cti21001-bib-0096){ref-type="ref"} A recent trans‐ethnic GWAS incorporating 86 640 individuals of European descent and 9846 individuals of East‐Asian, Indian or Iranian descent also highlighted a shared genetic risk across European and non‐European cohorts for most IBD risk loci, although genetic heterogeneity was observed -- both in terms of allele frequency and/or effect size -- between at several loci, including *NOD2*,*TNFSF15*,*ATG16L1*,*IL23R* and *IRGM*.[12](#cti21001-bib-0012){ref-type="ref"} In contrast, a GWAS in 2345 African Americans with IBD confirmed known risk loci but did not reveal any new variants associated with CD susceptibility.[97](#cti21001-bib-0097){ref-type="ref"} Clearly, larger studies will be necessary to better explore the commonalities and differences in the genetic variance of CD between populations, and these should ideally be performed using GWAS chips that are predicated upon the haplotype structure of the population being studied or whole genome sequencing, so as not to overlook the contribution of variants that are specific to non‐Caucasian populations.
Pharmacogenetics {#cti21001-sec-0009}
================
Aside from disease susceptibility, GWASs have also been used to try to identify genetic variants that are associated with specific side effects to medications commonly used to treat CD. Interest in this area was initially driven by studies in other fields that identified low‐frequency variants with large effect sizes that were responsible for well‐recognised side effects[98](#cti21001-bib-0098){ref-type="ref"} and by previous work that had demonstrated the clinical value of genotyping for mutations in *TPMT* that alter the risk of thiopurine‐induced myelosuppression.[99](#cti21001-bib-0099){ref-type="ref"} GWAS studies have since identified genetic variants in *NUDT15* that alter the risk of thiopurine‐induced myelosuppression,[100](#cti21001-bib-0100){ref-type="ref"} and in the MHC that alter the risk of thiopurine‐induced pancreatitis (*HLA‐DQA1\*02:01‐HLA‐DRB1\*07:01*)[101](#cti21001-bib-0101){ref-type="ref"} and 5‐ASA‐induced nephrotoxicity (*HLA‐DRB1\*03:01*).[102](#cti21001-bib-0102){ref-type="ref"} Interestingly, the *HLA‐DRB1\*03* allele has also been associated with the development of antibodies against infliximab -- an anti‐TNF‐α monoclonal antibody that is one of the most effective treatments for CD. Patients carrying the risk haplotype were almost seven times more likely to develop antibodies, which could potentially neutralise the drug and lead to a loss of efficacy.[103](#cti21001-bib-0103){ref-type="ref"}
In addition to studying the genetic contribution to drug side effects, efforts have also been made to identify a genetic contribution to treatment response. So far, however, most of these studies have used a candidate gene approach, investigating individual genes or groups of genes -- often those linked to CD susceptibility -- rather than adopting a genome‐wide approach.[104](#cti21001-bib-0104){ref-type="ref"} Similar to disease susceptibility, it seems unlikely that a single variant will determine the efficacy of CD therapies, and therefore, a genome‐wide approach will be important. Moreover, there is no reason to suspect that variants influencing response to treatment would be the same as those that alter disease susceptibility, and thus, it was unsurprising when a polygenic risk score based on 140 CD risk loci did not associate with response to anti‐TNF therapy.[105](#cti21001-bib-0105){ref-type="ref"} To date, a genome‐wide study of response to anti‐TNF therapy has not been performed in IBD, although a study based on the Illumina immunochip (a custom designed genotyping chip containing variants that have been associated with autoimmune diseases) did provide some encouraging results,[106](#cti21001-bib-0106){ref-type="ref"} though further validation and larger independent discovery cohorts will be important. In rheumatoid arthritis (RA), such a study has already been performed and identified eight loci that were associated with response to infliximab.[107](#cti21001-bib-0107){ref-type="ref"} A similar study has also been reported in abstract form for ustekinumab, an anti‐IL12/23 antibody, in which two loci were shown to be associated with response to therapy in CD patients.[108](#cti21001-bib-0108){ref-type="ref"}
In summary, although attempts to understand the genetic contribution to side effects or treatment response are far less advanced than equivalent studies in disease susceptibility, early studies have provided plenty of reason for optimism. Indeed, if genome‐wide approaches were to be adopted in suitably powered cohorts, it seems probable that genetic variants will be discovered that could both shed light on the biology responsible for responses to treatment and also potentially provide useful biomarkers for screening.
Subphenotypes: moving beyond disease susceptibility {#cti21001-sec-0010}
===================================================
Despite the success of GWAS studies into the genetic contribution to disease susceptibility, there are several other aspects of CD biology that have been proposed to have a genetic component but which -- until recently -- had not been studied by GWAS. For example, the distribution of Crohn\'s disease within the intestine and the clinical course of disease following diagnosis (prognosis) have both been shown to follow similar patterns within families[109](#cti21001-bib-0109){ref-type="ref"} but have been largely overlooked in favour of successively larger meta‐analyses into disease susceptibility. Part of the reason for this has been the assumption that susceptibility variants would also influence other aspects of disease.[110](#cti21001-bib-0110){ref-type="ref"} For example, it was assumed that the total burden of susceptibility variants would determine disease course, so that individuals who carry more risk SNPs would experience a worse prognosis. This hypothesis has been shown to be correct for qualitative traits such as height,[111](#cti21001-bib-0111){ref-type="ref"} but in CD -- and other diseases -- it would only be correct if susceptibility and prognosis were on a continuous spectrum and thus influenced by the same variants. If, however, this assumption is incorrect, then it would be very unlikely for SNPs, which influence disease prognosis to be identified through comparison of unstratified cases with controls.[112](#cti21001-bib-0112){ref-type="ref"} Instead, it would be necessary to directly compare subsets of patients based on phenotypic differences -- a so‐called within‐cases analysis (Figure [3](#cti21001-fig-0003){ref-type="fig"}).
{#cti21001-fig-0003}
To date, there have only been a few examples of using within‐cases analyses in CD genetics. The largest study was performed by the International IBD Genetics Consortium and investigated the contribution of a large number of autoimmune disease‐associated SNPs to CD distribution, age of onset and behaviour (i.e. inflammatory, stricturing or fistulating). Although this identified little or no genetic association with disease behaviour, it did identify three loci that were associated with disease location (*NOD2*,*MHC* and *MST1*) and showed that a genetic risk score representing the sum of all known risk alleles for IBD showed a strong association with disease location.[113](#cti21001-bib-0113){ref-type="ref"}
Despite the importance of CD prognosis in determining patient well‐being, most of the studies into the genetic contribution to prognosis have focused on small numbers of susceptibility SNPs in relatively small numbers of patients and have unsurprisingly provided inconsistent results.[114](#cti21001-bib-0114){ref-type="ref"}, [115](#cti21001-bib-0115){ref-type="ref"}, [116](#cti21001-bib-0116){ref-type="ref"} One of the few replicable associations identified was between variants in *NOD2* and need for surgery,[117](#cti21001-bib-0117){ref-type="ref"} although this was subsequently shown to be entirely driven by the association between *NOD2* and ileal disease (which is most commonly treated with surgery). Indeed, if this analysis is stratified by disease location, then no association between disease course and *NOD2* variants is detectable.[113](#cti21001-bib-0113){ref-type="ref"} For this reason, we elected to investigate the genetics of CD prognosis using a within‐cases analysis in which the genetic profiles of patients with contrasting courses of CD would be compared. This was first done as a candidate gene study and identified a noncoding SNP in *FOXO3* that was not a disease susceptibility variant, but which was associated with a milder course of CD[118](#cti21001-bib-0118){ref-type="ref"} -- an association that has since been replicated.[119](#cti21001-bib-0119){ref-type="ref"}, [120](#cti21001-bib-0120){ref-type="ref"} Functional studies into the biological consequences of this SNP, which does not affect disease susceptibility, identified a FOXO3‐driven pathway that abrogated inflammatory responses in monocytes via TGFβ1 and led to reduced TNF‐α and IL‐6 production in carriers of the mild CD‐associated allele.[118](#cti21001-bib-0118){ref-type="ref"} Interestingly, this SNP was also shown to associate with good prognosis in RA (another TNF‐α‐driven disease[121](#cti21001-bib-0121){ref-type="ref"}) and with poor prognosis in malaria (in which TNF‐α is anti‐parasitic).[118](#cti21001-bib-0118){ref-type="ref"} Since then, this variant has also been independently associated with clinical outcome in tuberculosis,[122](#cti21001-bib-0122){ref-type="ref"} another disease in which TNF‐α is known to be important. Based on this result, we then extended the analysis to a genome‐wide level and identified a further three loci that were significantly associated with prognosis in CD (*XACT*, a region upstream of *IGFBP1* and the MHC region).[120](#cti21001-bib-0120){ref-type="ref"} Strikingly, none of these variants were associated with disease susceptibility, and conversely, none of the CD susceptibility variants were associated with prognosis in our analysis, either individually or collectively. This demonstrated that the genetic contribution to prognosis comes from loci that are distinct from those that drive disease development, which in turn has important implications for our understanding of disease pathogenesis and could provide new opportunities for drug development and/or personalised medicine. In the future, larger within‐cases analyses will be important to further resolve the genetic contribution to clinically important disease subphenotypes, but the success of these will critically depend on there being detailed, high‐quality and consistent phenotypic data, else they are likely to provide (falsely) negative results.
Conclusions {#cti21001-sec-0011}
===========
During the past decade, our understanding of CD pathogenesis has benefitted greatly from the advent of GWAS -- success that has been possible thanks to large‐scale international collaboration. This has resulted in several novel insights into disease biology, which are now being investigated as therapeutic targets. However, it is important not to think that the job is done. There is much work left to do in order to fulfil the original goals of GWAS and learn more about disease biology, from determining the functional consequences at each associated locus to exploring genetic risk in other populations to identifying the genetic contribution to other important aspects of disease biology, such as prognosis. Much has been accomplished since the first CD GWAS 10 years ago, but much more should be accomplishable in the next 10 years if we make the most of the discoveries to date.
BV is a doctoral fellow of the Research Foundation Flanders, Belgium (11Y9418N). KGCS is an NIHR Senior Investigator. JCL is supported by a Wellcome Trust Intermediate Clinical Fellowship (105920/Z/14/Z).
We declare no conflict of interests.
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1. Field of the Invention
This invention relates to vehicular semi-automatic mechanical transmission systems and, in particular, to semi-automatic mechanical transmission systems of the type providing partially automatic implementation, including an automatic shift into neutral upon a driveline torque break or torque reversal condition, of preselected shifts and having at least one automatic preselect mode of operation wherein ratio changes are automatically preselected by the system central processing unit.
More particularly, the present invention relates to semi-automatic transmission systems of the type described above wherein, in the operator selected automatic preselection mode of operation, if vehicle speed (output shaft speed) remains substantially constant (i.e. if, for upshift conditions, output shaft acceleration does not exceed a first reference value, or, for downshift conditions, output shaft deceleration does not exceed a second reference value) then automatic preselection of shifts and automatic shifts into sustained neutral are prevented to prevent unexpected/undesired transmission shifts into sustained transmission neutral.
Still more particularly, the present invention relates to semi-automatic transmission systems of the type described above wherein, if engine or input shaft speeds are between certain values, the values of the first and second reference values will vary as a function of engine or input shaft speed.
2. Description of the Prior Art
Fully automatic transmission systems, both for heavy-duty vehicles such as heavy-duty trucks, and for automobiles, that sense throttle openings or positions, vehicle speeds, engine speeds, and the like, and automatically shift the vehicle transmission in accordance therewith, are well known in the prior art. Such fully automatic change gear transmission systems include automated transmissions wherein pressurized fluid is utilized to frictionally engage one or more members to other members or to a ground to achieve a selected gear ratio as well as automated mechanical transmissions utilizing electronic, hydraulic, and/or pneumatic logic and actuators to engage and disengage mechanical (i.e. positive) clutches to achieve a desired gear ratio. Examples of such transmissions may be seen by reference to U.S. Pat. Nos. 3,961,546; 4,081,065; 4,361,060 and 4,551,802; the disclosures of which are hereby incorporated by reference.
Such fully automatic change gear transmissions can be unacceptably expensive, particularly for the largest heavy-duty vehicles which are not typically sold in high volumes. Additionally, those automatic change gear transmissions utilizing pressurized fluid and/or torque converters tend to be relatively inefficient in terms of power dissipated between the input and output shafts thereof.
Semi-automatic transmission systems utilizing electronic control units which sense throttle position, engine, input shaft, output shaft and/or vehicle speed, and utilize automatically controlled fuel throttle devices, gear shifting devices and/or master clutch operating devices to substantially fully automatically implement operator manually selected transmission ratio changes are known in the prior. Examples of such semi-automatic transmission systems may be seen by reference to U.S. Pat. Nos. 4,425,620; 4,631,679 and 4,648,290, the disclosures of which are incorporated herein by reference.
While such semi-automatic mechanical transmission systems are very well received as they are somewhat less expensive than fully automatic transmission systems, allow manual clutch control for low speed operation and/or do not require automatic selection of the operating gear ratio, they may be too expensive for certain applications as a relatively large number of sensors and automatically controllable actuators, such as a master clutch and/or a fuel throttle device actuator, are required to be provided, installed and maintained.
Many of the drawbacks of the prior art are overcome or minimized by the previous provision of a semi-automatic shift implementation system/method for a mechanical transmission system for use in vehicles having a manually or partially automatically controlled engine throttle means, and a manually only controlled master clutch. The system has, preferably, a manual preselection mode wherein shifts are manually preselected and at least one mode of operation wherein the shifts to be semi-automatically implemented are automatically preselected and includes a control/display panel or console for operator selection of operation in the automatic preselection mode and indication of automatic preselection of upshifts, downshifts or shifts into neutral. An electronic control unit (ECU) is provided for receiving input signals indicative of transmission input and output shaft speeds and for processing same in accordance with predetermined logic rules to determine, in the automatic preselection mode, if an upshift or downshift from the currently engaged ratio is required and to issue command output signals to a transmission actuator for shifting the transmission in accordance with the command output signals.
The control/display device will display the selected but not yet implemented shift as well as the current status of the transmission, and, preferably will allow the operator to select/preselect a shift into a higher ratio, a lower ratio or into neutral. Preferably, the control device will also allow a manually or an automatically preselected shift to be cancelled.
In both the manual and the automatic preselection modes, when a ratio change is manually or automatically preselected, the transmission will automatically be urged or biased to shift, upon a driveline torque break or reversal, to neutral and will then shift to the selected ratio only upon the operator manually causing a substantially synchronous condition to exist.
In accordance with the previously proposed control, a control system/method for a vehicular semi-automatic mechanical transmission system for partially automatic implementation of manually and automatically preselected transmission shifts was provided which did not require throttle or clutch actuators, and which required only two speed signal inputs. However, this system was not totally satisfactory as, after a long period of relatively stable vehicle operating conditions, i.e. vehicle speed substantially constant or changing at less than a predetermined rate, an automatic preselection of automatic shifting of the transmission into, and remaining in, neutral may be undesired, unexpected and/or startling to the operator. This can occur during unintended torque breaks caused by cresting a hill, bumps in the road, and similar occurences.
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A.Thomas Levin is a Member of the law firm of Meyer, Suozzi, English & Klein P.C. located in Garden City.
In addition to serving as General Counsel to the firm, he is Chair of the firm’s Local Government, Land Use and Environmental Impact Review practice and the Professional Responsibility practice.
He originated and chairs the firm’s Veterans’ Scholarship Program at Nassau Community College. Mr. Levin represents private and public sector clients in the fields of local government law, land use regulation, environmental review compliance, cable television franchising, municipal and commercial litigation and appeals, and matters relating to professional responsibility, ethics and disciplinary proceedings.
He is currently a member of the Executive Committees of the NYSBA Local and State Government Law, International and 50+ Sections.
He also serves or formerly served, as Chair, member or Executive Committee Liaison to many committees of that Association, including the Law, Youth & Citizenship Committee, Special Committee on Law Firm Structure and Operations, Bylaws Committee, Committee on Legislative Policy, President’s Special Committee on Access to Justice, Special Committee on Court Structure and Judicial Selection, Special Committee on Legal Issues Affecting Same Sex Couples, Special Committee on Youth Courts, and the Nominating Committee. Mr. Levin also served as New York State Bar Association representative on the ABA House of Delegates and the New York State Independent Judicial Qualification Commission for the Tenth Judicial District.
In the public service field, Mr. Levin has been counsel to the Judiciary Committee of the New York State Assembly and the Joint Legislative Committee on the State’s Economy, and has been active in numerous community and charitable organizations. He is a member and former Chair of the Advisory Council of Nassau/Suffolk Law Services Inc. and currently serves as a member of the Advisory Board of the Land Use and Sustainable Development Law Institute at Touro Law School.
For more than 40 years, he has been pro bono general counsel to the Day Care Council of Nassau, Inc. and the Rosa Lee Young Childhood Center, and represents many other not-for-profit organizations.
In 2019, Mr. Levin was recognized as one of the Long Island Herald’s Top Lawyers of Long Island. Mr. Levin has been recognized by Who’s Who in American Law, Who’s Who in America, Who’s Who in the East and Who’s Who in the World.
In 2013, Mr. Levin was named an Access to Justice Champion by the Nassau County Bar Association for his dedication in providing legal representation on a pro bono basis. He was recognized by American Lawyer & Corporate Counsel Magazine as a “2013 Top Rated Lawyer for Energy, Environmental and Natural Resources”, and in 2013 and 2014 as “Top Rated Lawyer – Land Use and Zoning.”
In 2013 he also received the International Municipal Lawyers Association James H. Epps III Award for Service to Municipal Clients (2013).
Since 2012, Mr. Levin has been annually recognized as a New York Super Lawyer. He also received the Long Island Business News 2011 Leadership in Law Award and 2016 Lifetime Achievement Award, and in 2012 received the Vanguard in Diversity Award from the Metropolitan Black Bar Association for his accomplishments in promoting diversity in the legal profession.
Mr. Levin is rated “AV Preeminent” by Martindale-Hubbell, the highest level in professional excellence, and was recognized by Long Island Pulse Magazine from 2010-2014 as one of the region’s “Top Legal Eagles.”
He was also the recipient of the “Commitment to Justice” Award presented by the Nassau/Suffolk Law Services Committee in 2002, and has been recognized as an “Empire State Counsel” by the New York State Bar Association annually since 2006 for the strong support he has given to pro bono services, his outstanding leadership in the legal community, and his devotion to improving the justice system on Long Island. | https://theislandnow.com/a-thomas-levin-member-of-the-law-firm-of-meyer-suozzi-english-klein/ |
Predicting vocal outcome by means of a vocal endurance test: a 5-year follow-up study in female teachers.
Investigate whether vocal problems in future professional activities can be predicted by early laryngeal and phoniatric evaluation and whether a vocal endurance test can contribute to this evaluation. Five-year follow-up study of 30 female education majors, initially documented with a standard voice assessment and a vocal endurance test. Measurements before and after vocal endurance testing were compared and related to the vocal outcome 5 years after the initial testing. Voice assessment included perceptual evaluation, airflow measurements, Fo and SPL measurements, voice range profile and laryngeal (stroboscopic) examination. The Standard Tolerance Test, as recommended by the Union of European Phoniatricians, was followed. This data set was completed with a questionnaire concerning the subjects' vocal behavior. This questionnaire was repeated 5 years later. No significant differences were found for ENT scores (laryngostroboscopy) (P = .018). Logistic regression was used to determine a relationship between initial observations and the final outcome. The role of an endurance test as used in this study is negligible for the prediction of vocal outcome. A combination of laryngeal examination, maximum phonation time, and perceptual evaluation, assessed prior to the endurance test, reveals a prediction of the vocal outcome with a specificity of 90% and a sensitivity of 70%.
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Episode 5 - Meditation and Mindfulness with Alex Knysh
In this week's episode, I talk to my very good friend Alex Knysh.
Alex is an Energy Coach and a Hypnosis Practitioner practicing in Sydney. She uses Coaching, Hypnosis, Reiki and other modalities and she gets great results with her clients when she works with them.
Meditation and Mindfulness are two similar yet different techniques that can be used separately or in conjunction with each other to promote peace and calm in all aspects of your life.
Listen to the episode right here.
You can learn more about Alex and the work she does here : | http://theseanstreetexperience.com/episode-5/ |
Accident Rates in Construction
The construction industry is one of the most hazardous industries in the UK. According to data from the Health and Safety Executive, construction sits at the number one spot for fatal injuries with a five-year average (2016/17 – 2020/21) of 36 fatalities, compared to the 28 fatal injuries in the agriculture, forestry and fishing industry over the same period. However, when you look at the fatal injury rate per 100,000 workers employed, construction is only third worst behind agriculture, forestry and fishing and the waste and recycling industry.
But the fatal injury rate in construction is around four times higher than the average rate across all industries, and accidents and illnesses are also common. Here’s a deep dive into what accidents in construction looked like in 2019/20.
Accidents/Injuries and Fatalities in 2019/20
Fatalities
In construction during the period of 2019/20, there were:
- 40 fatalities relating to construction workers.
- 4 relating to members of the public.
On average, there were 37 fatalities to construction workers and 5 to members of the public each year over the last 5 years. Almost half of the deaths over this time were due to falls from height.
The overall trend of fatal injuries in construction has been on a downward trend for the last few decades, likely due to increased safety measures and advances in safety equipment and technology. However, the numbers have been fairly consistent over the previous few years, with the number of fatalities to workers in 2018/19 being 38, and 6 for members of the public.
Ill health
Working in construction can also expose people to health-related issues due to time spent working with toxic materials or carrying heavy objects, causing spinal problems. The annual average work-related ill health for construction is thought to be 81,000 (new or long-standing), of which 57% were musculoskeletal disorders.
Around 3.5% of construction workers suffered ill health due to their work. However, this rate is not that different from the average for workers across all industries: 3.4%. The numbers are:
- 46,000 cases of musculoskeletal disorder.
- 21,000 cases of stress, depression or anxiety.
However, the rate of stress, depression or anxiety only accounts for 0.9% of workers in construction, significantly less than the all-industry average of 1.6%.
Other illnesses include occupational respiratory disease like asthma, which affects 0.7 per 100,000 workers on average. Contact dermatitis can also be a hazard to plasterers, bricklayers and other occupations in construction, with workers thought to suffer at more than twice the all-industry rate.
Cancers have also been researched in relation to the construction industry due to exposure to carcinogens. A study suggests that in the UK, around 46% of occurring mesotheliomas (a cancer that follows the inhalation of asbestos fibres) exists in men born in the 1940s who are associated with construction, with 17% attributed to asbestos exposure through carpentry work alone.
Non-fatal Injuries
The data for non-fatal injuries in construction estimates that there were 61,000 in 2019/20, of which 27% of them required over 7 days absence from work. This accounts for around 2.8% of construction workers across the industry suffering from some kind of injury, a significantly higher number than the all-industry rate.
Over the last three year period (2017/20), the most common kinds of injuries were:
- Slips, trips or falls on the same level – 32%
- Injuries while handling, lifting or carrying – 6%
- Falls from height – 32%
- Struck by moving object – 13%
However, like with fatalities, the overall trend over the years has been a reduction in the number of workplace injuries.
Safety Measures in Construction
Due to the risk of injury, illness and fatalities in the construction industry, it’s no wonder there are such stringent laws and regulations that outline how work can be carried out safely and in a way that minimises risk to both workers and members of the public. Falls from height are the number one cause of fatalities in construction and a major cause of injury. To protect workers from falling while working at height, they must adhere to the Work at Height Regulations 2005.
This regulation lays out that any working at height must be sufficiently planned, supervised and carried out by competent people, including having the right kind of equipment for the job. It states that working at height should only be done when working at ground level is impossible, and risks must be assessed and controlled.
Contingency plans can be put in place with the use of personal protection like a fall arrest system or fall restraint system, or you can utilise collective protection like a permanent or temporary freestanding guardrail. More straightforward working at height can be done with something as simple as a ladder, but safety can still be improved using a fall arrest ladder or a companionway ladder.
At Altus Safety, we can provide you with a complete working at height and roof access solution. Whether you need roof edge protection or roof walkways, or abseiling anchors, we can help. Contact us today to find out more. | https://altussafety.co.uk/accident-rates-in-construction/ |
Picture this… You are four scientists, a neuroscientist and a best selling author, a Professor of Biology and Science, an Assistant Professor of Psychiatry and a former grad student.
All with a great passion for music…
So how do you combine this and at the same time use your research and findings as a basic for your songs. You form a rock band…!
What a way to publish – and to a target group that might not be so into your scientific papers…
And of course you name your group The Amygdaloids – The amygdala is a part of your brain, more precisely he limbic system, and shown in research to perform a primary role in the processing and memory of emotional reactions. | https://lovehateandmarketing.com/2011/02/04/neuroscience-meets-rock-roll/?replytocom=23 |
Find sitters, walkers or groomers for dogs, cats & more - select from 24,467 pet sitters near you.
I am a 33 year old freelance writer and animal carer living in Peckham. I ran a small animal rescue project caring for abandoned cats and kittens, from my home in Central Viet Nam for two years and more recently have volunteered for other animal rescue projects. I am active in campaigning for animal welfare, and periodically raise money for different campaigns. I have three years experience in medication management and admitsration, animal (specifically feline) behaviour, trauma recovery and a lifetime's experience in living with and caring for animal friends. I have raised ferrets, mice, rabbits, guinea pigs, rats and hamsters, and shared my life with many cats and dogs! I offer overnight sitting across London, and a walking/feeding/company service to animals locally. I can provide both character and professional references.
I have always been very passionate about animals. I have had many of my own but I have also taken care of pets for a living. The first animal I took care of was a cat. I learned her personality and managed to tame and relax her when she was having a difficulty feeling comfortable in her own environment which caused her to appear quite aggressive to other animals and humans around her. I have also taken care of multiple dogs, including walking, feeding and keeping them company as well as grooming them. I am also experienced with reptiles, such as snakes. Last but not least, due to my seven years of horse riding experience, I learned how to manage horses as well. I am also very passionate about bats and other exotic animals as such. I would absolutely love to continue working with animals in the future.
Looking for lovely dogs to spend time with!
Hey I’m a animal lover!
Hi! I am a student who loves animals. I have two cats of my own, and I have grown up around animals. I understand and appreciate the care and love they need. Therefore, when you're not here, I would like to provide that attention!
I was lucky to grow up in a family with many pets. Throughout my childhood I was able to take care of bunnies, cats and dogs. When it comes to dogs, I am very passionate and sensitive concerning their well-being. Long walks and a loving friendship are vital for their happiness. I understand if your pet needs any special treatment and I will do my best to follow any instructions.
I moved to London about a year ago but sadly had to leave my Tibetan Terrier x spaniel behind with my parents. I used to work at a cattery and I have grown up with dogs so I have experience with both cats and dogs! I have also owned rabbits, hamsters, fish (not tropical) and guinea pigs. I have experience with very nervous dogs too as my old Tibetan terrier had a few genetic health issues. I am looking for a furry friend of any size, age and breed to walk or provide occasional day care for it overnight stays. I can also feed and take care of pets if you are going away for a period of time. I am more than happy to follow any rules you have for your pets whether it be keeping on the lead or training them to heal, feeding times and food allergies etc. I have done volunteer work for charities and animal centres so have some good experience with dogs and cats of all breeds, sizes and ages. I am currently training to be a jewellery designer so I am not available on Thursdays or fridays. I am free most weekends, evenings and some weekdays.
At the Norwich Dog Walking Service, we are dedicated to provide a quality service for your pets. Local to the NR3 area, we are available for long and short walks and dog and small animal pet sitting. Short runs also available. DBS checked. | https://www.care.com/en-gb/profiles/pet-care/london/southwark |
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Himalayan Musk Deer ‘Moschus chrysogaster’ is listed as ‘Vulnerable’ in IUCN red list of Threatened Species in Appendix I by CITES for Nepal.
It is found in the Annapurna Conservation Area (ACA) Mustang and Manang districts, Kanchhajung Conservation Area (KCA), Sagarmatha National Park, Langtang National Park, Shy Phokshundo National Park, Rara National Park, Khaptad National Park, Makalu Barun National Park and Manaslu Conservation Area, there is lacking the specific Musk deer research and conservation awareness programme.
People in the Himalayan have hunted musk deer for commercial purposes since the early seventies. In Mustang this remains the sole reason for the decline in the musk deer population. So that there is necessary to raise conservation awareness to local people for the conservation of musk deer and its associated ecosystem.
The aims of this project are to find out about population status, distribution, habitat utilization, past and present poaching activities/trade pattern, develop participatory conservation action plan and conduct conservation awareness programme in the ACA of Mustang districts of Nepal.
This project will be provided management prescription to ensure long-term survival of Musk deer in its natural habitat.
For more information contact: | https://www.rufford.org/rsg/projects/achyut_aryal |
John F. Dienelt, Esq., PIPER RUDNICK LLP, Washington, DC, Daniel M. Eliades, Esq., FORMAN HOLT ELLKDES LLC, North Rochelle Park, NJ, for Cendant Corp.
DECISION REGARDING OBJECTION TO CLAIM OF CENDANT CORP.
This order addresses the objection of Ardent Liquidating LLC ("Ardent") to the claim of Cendant Corporation ("Cendant"). The objection will be overruled.
I
Cendant is the parent of companies that, as franchisors, operate real estate brokerage franchise systems under the names of Century 21, ERA, and Coldwell Banker. Cais, Inc. ("Cais") was the predecessor-in-interest of one of the debtors in this case, and Cendant's claim arises from a contract with Cais.
In August 2000, Cais and Cendant entered into a contract (the "Agreement"). Cendant agreed that it would exclusively recommend Cais to the franchisees of Cendant's franchisors and the sales associates of the franchisees ("the Customers"), as a vendor of high-speed internet connection services. Although Cendant agreed to actively promote Cais as a vendor of such services, Cais itself was responsible for developing, producing, and disseminating marketing materials to promote its services.
Cais, as "Vendor," agreed that:
Access Fee. Vendor shall pay to Cendant, in immediately available funds, the sum of Seven Million Dollars ($7,000,000) (the "Access Fee") as compensation to Cendant for its selection of Vendor as a preferred vendor of the Services and for providing access to the Customers. The Access Fee shall be paid in fourteen (14) equal quarterly installments of Five Hundred Thousand Dollars ($500,000) each. The first payment shall be due at the time this Agreement is executed by the parties and each successive payment shall be due not later than the first day of the every third month thereafter during the Term (each November 2, February 2, May 2 and August 2). Said fee is fully earned upon payment and shall not be subject to refund or reduction regardless of the termination of this Agreement for any reason. In the event of a termination of this Agreement, other than for Vendor's breach, Vendor's obligation to pay the Access Fee shall cease. Termination of this Agreement shall not affect the rights and obligations of Vendor or any Customer under any then-existing service agreement between Vendor and such Customer.
Agreement § 3 (emphasis added). After paying an initial installment of $500,000 on the Access Fee, Cais failed to comply with its obligation to make $500,000 quarterly installment payments on the Access Fee. Cendant terminated the Agreement based on these defaults. The quarterly installments that had come due as of the date of termination stood at $1,500,000, and Ardent does not contest its liability for that $1,500,000. However, Cendant claims that it is owed an additional $5,000,000 on the Access Fee (that is, the full amount of the $7,000,000 Access Fee less $500,000 already paid and less $1,500,000 not disputed as being owed).
In addition, the Agreement provided that Cais would pay Cendant certain "recurring commissions" based on each customer hooked up to one of the internet services being sold by Cais. See Agreement § 4. Those recurring commissions included in Cendant's proof of claim are not in dispute.
II
Ardent objects that this $5,000,000 is not owed based on five arguments. Applying the law of New Jersey, which governs the enforcement of the Agreement, the court will reject all of Ardent's arguments.
A.
Ardent argues, first, that:
There is nothing in the Agreement that entitles Cendant to seek payment of an additional $5 million that was not earned prior to Cendant's termination of the Agreement. Indeed, the Agreement states that each portion of the fee "is fully earned upon payment."
Ardent's Reply at 1. Section 3 of the Agreement called for the quarterly installment payments of the Access Fee to be paid at the start of each quarter. Accordingly, if the Agreement were terminated by Cais in the midst of a quarter (pursuant to certain conditions permitting it to terminate the Agreement), "[s]aid fee is fully earned upon payment and shall not be subject to refund or reduction regardless of the termination of this Agreement for any reason." This quoted language would permit Cendant to retain the payment even though the Agreement was terminated in the midst of the quarter. Accordingly, this quoted language does not bear the interpretation that Ardent places upon it of demonstrating that upon termination of the Agreement by Cendant, no further quarterly fees would come due. Indeed, the following sentence evidences that only upon a termination other than for breach by Cais would the obligation to pay the Access Fee cease:
In the event of a termination of this Agreement, other than for Vendor's breach, Vendor's obligation to pay the Access Fee shall cease.
Agreement § 3 (emphasis added). Cendant terminated the Agreement for Cais's breach, and, accordingly, under this sentence, Cais's obligation to pay the Access Fee did not cease. Even without that sentence, Cais's obligation remained an obligation that it would have had to perform had the contract not been terminated based on its default, and hence would be a measure of the general damages suffered by Cendant, as discussed with respect to other arguments.
The Agreement elsewhere expressly states that certain obligations are to survive the termination of the Agreement. See Agreement § 13(d) regarding confidentiality and nondisclosure obligations. However, this simply makes clear that the parties remain subject to such obligations and required to perform them (including the party not in default who generally is excused from future performance, but not as to promises of confidentiality which implicitly survive termination); it relates, in other words, to a matter (confidentiality) whose survival the parties might want to make explicit instead of implicit. It does not purport to address an issue of damages upon termination, the wholly different issue that Cendant's claim presents, as to which there would be no doubt that damage claims survive, including the claim for the unperformed promise of paying the Access Fee.
Moreover, the Agreement expressly provides for waiver of certain claims. So it could just as illogically be argued that the absence of an express waiver demonstrates that the damage remedy survived. In other words, the absence of an express waiver of the Access Fee creates an illogical inference of non-waiver that would cancel out any illogical inference of non-survival drawn from the absence of an express provision for the survival of the Access Fee (as an obligation or as an element of damages).
See Agreement § 5(d)(i) regarding claims against Cendant for losses arising out of any occurrence relating to the services Cais was to provide to Customers) and Agreement § 5(e) (waiving claims for indirect, special or consequential damages).
In any event, the express provision for survival of certain obligations fails to negative the clear intent expressed in Agreement § 3 that only a termination other than one based on a breach by Cais would relieve Cais of the obligation to pay the full Access Fee, an intent that can only mean that Cais's obligation was to survive, not that it was to cease. It was unnecessary expressly to state that which was clearly intended and expressed in the limitation of when Access Fee obligations would cease.
B.
Ardent argues, second, that the $5,000,000 claim is a form of lost profits that was waived by the express waiver in § 5(e) of the Agreement of "indirect, special, or consequential damages," including lost profits. However, Cendant's claim based on the Access Fee is for "direct or general damages," as that term is used in New Jersey law, in contrast to "indirect, special or consequential damages" (terms that all mean the same thing: the opposite of general or direct damages). The distinction between general damages and special damages was recognized by the observation in Marcus Co., Inc. v. K.L.G. Baking Co., Inc., 3 A.2d 627, 631 (N.J. 1939), that a party to a contract:
Section 5(e) of the Agreement provided:
Neither party shall be responsible to the other party for indirect, special or consequential damages under any tort (including negligence), contract, strict liability or other legal or equitable theory in connection with each party's performance of its obligations under this Agreement including lost profits or interruption of business (regardless of whether a party has been advised of the possibility of or could have foreseen such damages). The limitation of liability provided under this subsection (e) shall not apply with respect to (i) third party claims and/or (ii) the willful misconduct or gross negligence of a party.
The distinction between "general or direct" damages and consequential (or special or indirect damages) was explained by the Supreme Court of New Jersey in a case involving a clause excluding consequential damages in a contract for the sale of goods:
Potential liability for consequential damages in commercial contexts, usually in the form of the buyer's lost profits from the use or resale of the goods in its business, is enormous in comparison to the contract price of the goods. On the other hand, the general or direct damages that a buyer may suffer upon a seller's breach are finite and can be gauged at a maximum amount either in terms of the contract price or market price of the goods to be sold. Potential consequential losses are a much different proposition. They can exceed, and most likely will exceed, the value of the goods by an unknown quantum, depending not so much on the actions and machinations of the seller as on the individual operating structure of the buyer and on the buyer's contracts and relationships with third parties.
Kearney Trecker Corp. v. Master Engraving Co., 527 A.2d 429, 433 (N.J. 1987) (quoting Anderson, "Failure of Essential Purpose and Essential Failure on Purpose: A Look at Section 2-719 of the Uniform Commercial Code," 32 Sw. L.J. 759, 774 (1977)) (emphasis added).
See Perth Amboy Iron Works. Inc. v. Am. Home Assur. Co., 543 A.2d 1020, 1032-33 (N.J.Super.Ct. App. Div. 1988) (drawing distinction between direct damages and consequential damages) Seaman v. U.S. Steel Corp., 400 A.2d 90, 92 (N.J.Super.Ct. App. Div. 1979),certif. denied, 405 A.2d 826 (N.J. 1979) (consequential and special damages are same).
is under a duty to respond in damages for such losses as would probably result in the ordinary course of things from a breach of the contract under the special circumstances known to the parties at the time it was made. Such are ordinarily considered by the law as reasonably within the contemplation of both parties to the contract. Where the special circumstances are not known to the party chargeable with the breach, the law deems . . . that he "had in his contemplation the amount of injury which would arise generally, and in the great multitude of cases not affected by any special circumstances, from such a breach of contract," [quoting Hadley v. Baxendale, 9 Ex. 341, 156 Eng. Rep. 145, 151 (1854)] and his liability is measured accordingly.
[Citations omitted; emphasis added.]
In Marcus Co., the breach was of a sale of goods, but the rule applies to other contracts as well. See e.g., Weiss v. Revenue Bldg. Loan Ass'n, 182 A. 891, 892-93 (N.J. 1936) (applying same rule to a breach of a contract for lease of real property). As explained in Ebasco Services. Inc. v. Pa. Power Light Co., 460 F. Supp. 163, 213 n. 62 (E. D. Pa. 1978):
Although the primary issue in Hadley was recoverability, the case also offered guidance on categorization. That is, Hadley focused on the foreseeability necessary in order to recover consequential damages, but in doing so it characterized general and consequential damage. Under Hadley and the contract case law that has followed it, ordinariness or directness in the usual case is the hallmark of a general or direct damage; presence of peculiar circumstances signals special or consequential damages.
Consequential damages include such damages as lost profits that the non-defaulting party would have earned after performance had the defaulting party performed. See George H. Swatek, Inc. v. N. Star Graphics, Inc., 587 A.2d 629, 631 (N.J.Super. App. Div. 1991). The loss arising from Cais's nonperformance of the obligation to pay the Access Fee is a general or direct damage, the performance called for by the contract, not a loss of profits that Cendant might have realized after the fact had Cais performed that obligation.
As such, the damages, of course, readily satisfy the requirements of foreseeability, the second prong of Hadley (see n. 7, supra). That Cais may not have expected to default does not negate the foreseeability of the direct damage to Cendant arising from Cais's non-performance of its obligation to pay Cendant the Access Fee.
C.
Ardent argues, third, that Cendant suffered no actual damages justifying recovery of the $5,000,000 that came due only after the date of termination of the Agreement because Cendant was not required to perform in the post-termination period. Although Cendant's performance under the contract from which it was excused by reason of termination is relevant to the issue of measuring damages, it does not alter the outcome.
1.
Essentially, Ardent's argument is that it is unreasonable to hold Cais to the obligation to pay the Access Fee when Cendant was not required to perform its end of the bargain after termination of the Agreement. The court has no power to produce a fairer or more reasonable result when the contract's terms are clear and unambiguous. See 11 Richard A. Lord,Williston on Contracts § 32:11 at nn. 92 and 93 (4th ed. as updated July 2003) ("the courts will not indulge in artificial interpretations or abnormal implications in order to save a party from a bad bargain. The court may not, under the guise of interpretation, make a new contract for the parties.") (footnotes omitted).
Although in interpreting contracts, "the most fair and reasonable construction, imputing the least hardship on either of the contracting parties, should be adopted [citation omitted], so that neither will have an unfair or unreasonable advantage over the other,"Tessmar v. Grosner, 128 A.2d 467, 471 (N.J. 1957), that quoted rule only applies when the contract is susceptible of differing interpretations:
where the terms of a contract are clear and unambiguous there is no room for interpretation or construction and the courts must enforce those terms as written. Kampf v. Franklin Life Ins. Co., 33 N.J. 36, 43, 161 A.2d 717 (1960); Levison v. Weintraub, 215 N.J. Super. 273, 276, 521 A.2d 909 (App.Div.), certif. denied, 107 N.J. 650, 527 A.2d 470 (1987). The court has no right "to rewrite the contract merely because one might conclude that it might well have been functionally desirable to draft it differently." Id.; Brick Tp. Mun. Util. Auth. v. Diversified R.B. T., 171 N.J. Super. 397, 402, 409 A.2d 806 (App.Div. 1979). Nor may the courts remake a better contract for the parties than they themselves have seen fit to enter into, or to alter it for the benefit of one party and to the detriment of the other. James v. Federal Ins. Co., 5 N.J. 21, 24, 73 A.2d 720 (1950).
J.L. Davis Assocs. v. Heidler, 622 A.2d 923 (N.J.Super.Ct. A.D. 1993). Here the contract is insusceptible of any interpretation other than that even if Cendant terminated the Agreement based on Cais's default, Cais's required performance included payment of the Access Fee. Whether that required performance gives Cendant the right to recover the Access Fee as damages is, however, a different issue, as discussed below.
2.
New Jersey contract law recognizes that contract damages place an injured party in the same position that the party would have occupied had the other party performed as promised. See In re Liquidation of Integrity Ins. Co., 685 A.2d 1286, 1290 (N.J. 1996); 525 Main St. Corp. v. Eagle Roofing Co., 168 A.2d 33 (N.J. 1961). Here, that means that an element of Cendant's damages is the amount of the Access Fee that Cais failed to pay, however bad, in hindsight, that makes the deal that Cais struck.
3.
This does not mean that the performance of which Cendant was excused (upon terminating the Agreement) is irrelevant. Although Cendant is entitled to the value of performance, that value is measured by "the performance of both parties and not the value of the defendant's performance alone." 24 Richard A. Lord, Williston on Contracts § 64.3 (4th ed. as updated May 2003). That is to say, in awarding contract damages, the injured party's recovery should be reduced by expenses of performance of which it was excused by reason of the termination of the contract. See Magnet Resources, Inc. v. Summit MRI, Inc., 723 A.2d 976, 985 (N.J.Super. App. Div. 1998).
However, Ardent has not shown that Cendant's active promotion of Cais's services would have cost Cendant anything. Under F.R. Bankr. P. 3001(f), Cendant's claim is prima facie valid, and in the absence of evidence that Cendant avoided any expense, the claim remains valid in the full amount.
For example, Cendant may already have been sending a newsletter periodically to its franchisors' franchisees which would have been the vehicle for making such promotions. Cais itself was responsible for preparing and disseminating marketing materials.
D.
Ardent argues, fourth, that the $5,000,000 sought by Cendant for the post-termination period is in the nature of liquidated damages, and is unallowable by reason of its penal character. Liquidated damage provisions are stricken as penal if they are not a reasonable forecast of just compensation for the actual injury resulting from the breach.Wasserman's Inc. v. Township of Middletown, 645 A.2d 100, 105, 108-109 (N.J. 1994).
However, liquidated damages are by definition a substitute for actual damages. Here, Cendant seeks only its actual damages (its evidence being the loss of the Access Fee Cais promised it would pay, with no countervailing evidence introduced by Ardent that Cendant mitigated its damages) not some liquidated amount agreed to by the parties in lieu of computing the actual damages. Citing Met Life Captial Fincl. Corp. v. Washington Ave. Assocs., 732 A.2d 493 (N.J. 1999), and Westmount Country Club v. Kameny, 197 A.2d 379 (N.J.Super. App. Div. 1964), Ardent states that under New Jersey law:
Damages for breach by either party may be liquidated in the agreement but only at an amount which is reasonable in light of the anticipated or actual harm caused by the breach, the difficulties of proof of loss, and the inconvenience or non-feasibility of otherwise obtaining an adequate remedy. A term fixing unreasonably large liquidated damages is void as a penalty.
See Met Life, 732 A.2d at 499 (emphasis added) (quoting the Uniform Commercial Code ("UCC") provision on liquidated damages, adopted in New Jersey as N.J.A.A. 12A:2-718, and embracing a similarly worded test from Restatement (Second) of Contracts § 356 (1981) that was adopted to harmonize the Restatement with the UCC provision). Again, the damages that Cendant seeks to recover are not stipulated damages in lieu of proof of actual damages, but its actual damages, and hence the test adopted inMet Life does not come into play.
Westmount provides a useful illustration of this principle, and a useful contrast to this case. In Westmount, a contract clause required Kameny to pay his fees for a one-year club membership, even though the membership was canceled mid-year. Westmount, 197 A.2d at 380-81.Westmount did not hold that a fixed periodic fee is an impermissible element in fixing actual damages, but only that the stipulated damage clause was unreasonable and hence a penalty, instead of permissible liquidated damages: Mr. Kameny ought to have been allowed to introduce evidence of mitigation of damages in fixing the actual damages.Westmount, 197 A.2d at 383-84. Unlike the club in Westmount, Cendant never contended that the periodic fee provision at issue is a stipulated damages clause precluding Ardent from presenting mitigation evidence. Ardent has simply failed to put on any evidence regarding mitigation of damages, and in default thereof the Access Fee is the appropriate amount of actual damages.
E.
Ardent argues, fifth, that Cendant has failed to show that it did not mitigate its damages (or that it took any steps to attempt to mitigate its damages). However, under New Jersey law, Ardent bears the burden of showing that Cendant mitigated its damages (or, if Cendant was required to attempt to mitigate its damages, that it failed to make such attempts). See Magnet Resources, Inc., 723 A.2d at 987 (applying the general rule set forth in dictum in Sommer v. Kridel, 378 A.2d 767 (N.J. 1977)). The intervention of bankruptcy does not alter that burden of proof. Raleigh v. Illinois Dept. of Revenue, 530 U.S. 15, 21 (2000) ("one who asserts a claim is entitled to the burden of proof that normally comes with it").
In any event, even if it is assumed instead that New Jersey law places on the non-breaching party the burden of proof on the issue of mitigation of damages, Cendant's claim is prima facie valid under F.R. Bankr. P. 3001(f). Ardent offered no evidence regarding mitigation of damages. Only had Ardent introduced such evidence would Cendant have been required (if New Jersey law indeed puts the burden of proof on the non-breaching party) to present evidence to negate Ardent's evidence.
See Lundell v. Anchor Construction Specialists, Inc., 223 F.3d 1035, 1039 (9th Cir. 2000); McGee v. O'Connor (In re O'Connor), 153 F.3d 258, 260 (5th Cir. 1998); Carlson v. United States (In re Carlson), 126 F.3d 915, 921-22 (7th Cir. 1997), cert. denied, 523 U.S. 1060 (1998); Franchise Tax Board of Calif. v. MacFarlane (In re MacFarlane), 83 F.3d 1041 (9th Cir. 1996), cert. denied, 520 U.S. 1115 (1997); Brown v. IRS (In re Brown), 82 F.3d 801, 805 (8th Cir. 1996); Juniper Dev. Group v. Kahn (In re Hemingway Transp., Inc.), 993 F.2d 915, 925 (1st Cir. 1993); Placid Oil Co. v. IRS (In re Placid Oil Co.), 988 F.2d 554, 557 (5th Cir. 1993); In re Fullmer, 962 F.2d 1463, 1466 (10th Cir. 1992); In re Allegheny International. Inc., 954 F.2d 167, 173 (3rd Cir. 1992); Wright v. Holm (In re Holm), 931 F.2d 620, 623 (9th Cir. 1991). | https://casetext.com/case/in-re-ardent-inc |
I informed the real estate agency that I should not pay the 1% deposit before applying for housing loan. Now, I have to take up the loan with high interest rate or lose the 1% deposit.
May I know under the Malaysia laws, can I request back my 1% deposit?
When I informed my agent that I was unable to service the loan monthly installments due to such high interest rate, he told me that I have a loan approved and all I need to do is sign and get the loan. I told him that there was no point for me to take up this loan cause in the end I couldn't afford it. He kept replying that I would only lose the 1% deposit and I was not the only one in such predicament, there are other applicants too.
How am I going to discuss with my agent as I cannot afford to paid the loan? And also, the number of loan applications rejected was more than approval.
Below are some of the terms stated inside the Letter of Offer to Purchase:
Offer to PurchaseAccording to term no. 5, I got 2 rejection letters, meaning I can get back my 1% deposit refund, but the agent said no refund, cause I got one approval letter.
3. By the Vendor(s), the Vendor(s) shall refund the Earnest Deposit received from the Purchaser(s)together with a compensation sum of equivalent amount which shall be shared equally between the Purchaser and [Real Estate Agency]. The Purchaser(s) reserved the rights to sue for specific performance and/or damages flowing therefrom and all costs and expenses Incurred thereto shall be borne by the Vendor(s).
4. The Purchaser(s) shall pay the balance of 10% deposit towards the purchase price upon execution of the formal Sale and Purchase Agreement and the balance purchase price shall be paid to the Vendor or the Vendor's Solicitors on or before the Completion Date, or the extended Completion Date as the case may be stipulated in the formal Sale and Purchase Agreement;
5. In the event the Purchaser's loan is not approved/obtained [evidencing two financial Institution rejection letters to the Vendor, the earnest deposit paid shall be refunded in full to the Purchaser by the Vendor free of interest;
6. That the above mentioned Property is sold at a "as is where is basis". Each party shall bear its own solicitors' cost.
Please advise me on this situation. | https://www.lawyerment.com/answers/questions/13496/buying-property-agency-refused-to-refund-deposit-as-one-bank-approved-while-two |
Global competence is an emergent and complex concept. The world is constantly changing and, with it, the knowledge, skills, and dispositions required to navigate the world continue to change. Within this context, World Savvy’s work to build the knowledge, skills, and dispositions for global competence requires ongoing adaptation and innovation. Educating for global competence is a complex process that cannot be achieved with a linear or stagnant approach, nor is it a ‘checklist’ of activities and knowledge. Evaluating our work and assessing global competence therefore necessitates an approach that accounts for this continuous development and change. In consultation with evaluation expert Michael Quinn Patton, World Savvy had adopted a utilization-focused developmental approach to evaluation and assessment.
To evaluate program experience, outcomes and impact, World Savvy collects qualitative and quantitative data from program participants through surveys, observations, interviews, focus groups, and case studies. We administer a post-program retrospective survey for students. In consultation with evaluation experts we have developed a survey instrument to accurately capture the changes in students’ global competence over the course of their participation in World Savvy programs. We also survey participating educators at the close of the program to measure both their own learning as a result of the professional development aspects of our programs, and their observations and impressions of their students’ learning and progress. This quantitative and qualitative evaluation will be supplemented with formal and informal observation in the classroom and anecdotes from educators; the triangulation of data will provide an accurate and holistic view of World Savvy’s impact. | http://www.worldsavvy.org/evaluation-assessment |
The SEM technique determines whether the dissertation model fits reasonably well to the data and evaluates the contribution of each independent variable to each of the dependent variables. Using structural equation modeling for your analysis also allows you to compare alternative models and evaluate differences between groups.
Students are encouraged to develop their own ideas for their dissertation. Many use work-based experiences and/or career aspirations to form the basis for their dissertation. Students submit a dissertation proposal using a structured application form to frame their ideas and methodology. They then receive written feedback from three dissertation tutors. This process is intended to ensure that the student’s ideas have the potential to meet the requirements for the dissertation, within the time permitted and the resources available to the student. Once students have a satisfactory proposal for their dissertation, they are put in touch with a supervisor to support the remainder of their work. Most supervisors are based within the University of Manchester. Senior academics are self-selected for this role, to match them with the student’s dissertation topic and the selected dissertation model. All supervisors are invited to training sessions and/or are sent written guidance. They also have access to the same learning and support materials as the student. Supervisors can seek additional support at an individual level from the course dissertation lead (RAH). As a guide, supervisors are expected to provide around 16-20 hours of supervisory support in total, over the academic year. This includes responding to student queries, giving feedback on their written work, and providing general guidance, information, and support. In the initial stage, supervisors are encouraged to provide an introductory email to their student, and to agree mutually acceptable methods for communication (e.g., email, telephone, Skype, Google+). Similarly, in the initial stages, students are encouraged to introduce themselves to their supervisor and to identify any immediate or potential future learning needs. The whole process is monitored by the course dissertation lead (RAH), who can also respond to individual queries and further support needs from students and their supervisor.
There was some variation in the levels of satisfaction with the course overall by the type of dissertation model students had chosen to do (Table 3). Most students expressed at least a positive experience. However, these findings are difficult to interpret because of the small number of students within each category and percentages have not been presented.
Check list & research dissertation model chapter 4 ..
The majority of questions used a four-point Likert scale. The analysis calculated frequencies and percentages for questions using the Likert scale. Fishers exact test was used to test for associations between levels of satisfaction and registration status, type of dissertation model, and level of contact with supervisor. Open ended/free text questions were used to obtain information on a number of themes. These were analysed using the constant comparative method (Maykut & Morehouse, 1994). Students were asked to estimate the amount of time they spent working on their dissertation overall, in numbers of hours which were then rounded up or down to the nearest whole number. This variable was not normally distributed and the Kruskal Wallis test was used to test for an association between overall satisfaction and the median time spent working on the dissertation. The study was conducted as part of a service evaluation. Ethical approval and participant signed consent was not required. Students could opt out by not completing the survey without giving any reason.
These CDS categories are not duplicated in the dissertation model.
Derrick Deloatch, Ed.D., John Hendron, Ed.D., Angie Kim, Ed.D., & Shawnya Tolliver, Ed.D.
*Note: Download includes submission synopsis & dissertation in practice; For a description of the VCU dissertation model, .
The 34 item questionnaire sought levels of satisfaction with the themes: (1) preparatory information, (2) study skills resources, and (3) supervision. Information was also collected on registration status (full or part time) and the type of dissertation model selected by the student. It was not possible to collect more detailed information on baseline characteristics as this could have broken the student’s anonymity.
Gallery Writing Theses and Dissertations [Choosing a Topic] .. | http://dissertation.tcdhalls.com/dissertation-model.html |
The invention discloses a laser radar data processing method and system. The method comprises the steps of obtaining a multi-frame two-dimensional depth map converted from laser radar original data and a filter determined according to a ratio of a transverse angle resolution to a longitudinal angle resolution of a laser radar; performing intra-frame compression on each frame of two-dimensional depth map according to a filter and a preset plane fitting algorithm to obtain multiple frames of intra-frame compressed two-dimensional depth maps; for one two-dimensional depth map group, performing inter-frame compression on the two-dimensional depth map group according to the difference between the two-dimensional depth map after the intra-frame compression of the second frame to the two-dimensional depth map after the intra-frame compression of the last frame in the two-dimensional depth map group and the two-dimensional depth map after the intra-frame compression of the first frame; and after inter-frame compression is carried out on all the two-dimensional depth map groups, overall compression is carried out on all the two-dimensional depth maps after inter-frame compression, and the two-dimensional depth map after overall compression is obtained. According to the invention, data compression can be realized from multiple angles, so that the data volume is reduced. | |
Charles Barkley, Patrick Ewing & the best players Michael Jordan blocked from winning an NBA championship
Michael Jordan led the Chicago Bulls to six championships in the 1990s, a run the ESPN documentary "The Last Dance" chronicled the last five weeks.
It's not just about the rings. It's about the rings other superstar NBA players didn't win because of the Bulls' reign over the league. Several stars from the first two Dream Teams do not have championships, and their legacies might have been different with that ring.
Whose legacy was impacted most? That’s an interesting question.
Sporting News looks at the six players whose legacies might be different had they been able to take down Jordan in either the Eastern Conference playoffs or NBA Finals to find the answer.
MORE: Michael Jordan's six championship Bulls teams, ranked
6. Shawn Kemp
"The Rainman" made six straight All-Star appearances from 1992-98 with Seattle, and he did it with ferocious dunks that were custom-made posters (ask Alton Lister). The Sonics — led by Kemp and Gary Payton shook off several playoff disappointments with a 64-18 record in 1995-96 — but they ran into the Bulls’ 72-win team in the NBA Finals.
Chicago won the series in six games. What if Seattle found a way that season? Perhaps Kemp doesn’t leave for Cleveland in 1997, where he made one All-Star appearance before fading into a role player with Orlando and Portland at the end of his career. Payton later won a ring with Miami.
5. John Stockton
Start an all-time greatest point guard ever discussion with your friends. How long does it take to get to Stockton? He is the NBA’s all-time leader in assists and ranks in the top 50 all time in scoring. He was also a member of the original Dream Team, where he had an uncanny way of staying out of the spotlight.
Stockton gets lost, in part, because Utah couldn’t get past the Chicago Bulls in the NBA Finals. Stockton’s reputation as a scrappy (dirty?) player endures to this day, but he would be more appreciated in those point-guard conversations with a championship ring.
MORE: Ranking Michael Jordan's Bulls championship teammates
4. Reggie Miller
Miller ranks second all-time in three-pointers made and is one of the greatest shooters of all time. He got Jordan’s attention in a fight in 1993, but his reputation was mostly based on the rivalry with the Knicks up until the 1997-98 season. Miller led the Pacers to the Eastern Conference finals – and he hit a buzzer beater in Game 4 that tied the series.
Indiana pushed the Bulls to seven games before losing, however. The Pacers would reach the NBA Finals two years later before losing to the Lakers — another team coached by Phi Jackson. Miller spent his entire 18-year career with the Pacers — but that loyalty never translated into a ring.
3. Karl Malone
"The Mailman" was a two-time MVP and ranks second in NBA history in points scored. He was a dominant power forward, original "Dream Team" and a durable player who played in 80 or more games in 17 of his 19 NBA seasons. Utah lost in the Western Conference finals in 1992, 1994 and 1996, and it wasn’t until 1997 that Malone broke through and reached the NBA Finals. Malone missed two clutch free throws in Game 1 against the Bulls, a game in which Scottie Pippen told him, "The Mailman doesn’t deliver on Sunday." Utah lost the NBA Finals in 1997 and 1998, and Malone chased a ring with the Lakers in his final season at age 40. It did not work out.
2. Patrick Ewing
You could make a strong argument Ewing should be No. 1 on this list. After all, Jordan tormented Ewing dating back to the college days at North Carolina and Georgetown. Ewing was a No. 1 pick, a 11-time All-Star and one of the most-skilled centers to ever play the game — and he did all that with the pressure of playing in Madison Square Garden. He won a college national championship and two gold medals with Team USA basketball. Jordan kept Ewing from getting that NBA ring.
The Bulls eliminated the Knicks from the NBA playoffs five times from 1988-96, including the Eastern Conference finals in 1993. New York had a 2-0 lead in that series. When Jordan retired in 1993-94, the Knicks finally beat the Bulls but lost to the Rockets in seven games in the NBA Finals. Ewing never got that close to a championship again.
1. Charles Barkley
Sir Charles was a 11-time All-Star who came to Philadelphia after their 1983 NBA Finals championship. The 76ers reached the Eastern Conference once in eight seasons there. Barkley went to Phoenix, won the NBA MVP award in 1993 and carried the Suns to the NBA Finals. Barkley played well, but the Bulls were too much and took the series in six games. Barkley spent four years in Phoenix and four more in Houston but was never able to get the championship ring.
Why is this different than Ewing? Barkley, a fixture on “Inside the NBA," is constantly reminded by Shaquille O’Neal and Draymond Green, among others, that he never won a championship ring. It does not make Barkley any less of a player, but it is yet another reminder of the decade that Jordan dominated in the 90s. | https://www.sportingnews.com/us/nba/news/charles-barkley-patrick-ewing-michael-jordan-nba-championship/2tbe37wmh60w1n21t1joc3mnn |
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1.. Introduction
================
Gait analysis is a widely used clinical tool for quantifying human walking ability, by identifying differences in gait patterns and parameters. Currently the most popular method of gait analysis is done with reflective skin markers and camera based motion analysis system such as Vicon (Vicon Motion Systems, Inc., Los Angeles, CA, USA). The combined use of stereo photogrammetry and reflective skin markers allows to calculate the joint kinematics and to assess the markers trajectories in time. However, the use of optical tracking systems has been hindered in practice by appropriate laboratory techniques, by the time necessary for the measurements, by the markers\' occlusion and the prohibitive costs. Furthermore, the worst drawback regards the subject\'s constrained freedom of movement, where the subject is required to move inside a restrained space and in a controlled environment \[[@b1-sensors-14-23230]\].
An alternative method for gait analysis is to use wearable sensor systems \[[@b2-sensors-14-23230]--[@b5-sensors-14-23230]\]. This method has the advantage of identifying human motion virtually anywhere, both indoors and outdoors. For instance, one of the outdoor applications made possible with the use of inertial sensors concerns the sport sciences field, such as during in-field motion capture measurements that do not allow the use of a markers-based motion analysis, as reported by Gastaldi *et al.* \[[@b6-sensors-14-23230]\]. However, these methods do not directly measure position, but only kinetic data (acceleration, angular velocity, magnetic fields, *etc.*) of body segments they are attached to. Therefore, translating the collected data into meaningful kinematic ones that can be used for diagnosing patients has been the challenge in the field of biomechanics. A sensor to body calibration procedure is needed in order to study joints kinematics, starting from the estimation of the body segment orientation. Tong and Granat \[[@b7-sensors-14-23230]\], calculated lower limb body segments orientation by integrating measured angular velocity from gyro sensors worn to the thigh and shank. However, integration caused errors to accumulate and caused the calculated values to 'drift' from the true value.
Many works in the past have reported methods to rectify this drift phenomenon. Takeda *et al.* \[[@b8-sensors-14-23230]\] developed an optimization algorithm to extract only the gravitational acceleration component from the cyclic patterns in acceleration data during gait. Thus, this enabled the calculation of the inclination of lower body segments during gait without the usage of gyro sensors. Liu *et al.* \[[@b9-sensors-14-23230]\] corrected the gyro drift by calculating the orientation of body segments from the acceleration during the mid-stance phase of gait. Favre *et al.* \[[@b10-sensors-14-23230]\] used acceleration data to compensate for drift in the angular velocity data in situations where gravitational acceleration is the only component measured. Almost all the proposed methods have assumed that the measured gait contained cyclic patterns, however these method would not be applicable for subjects with impaired mobility, where cyclic properties of gait might not be apparent.
An alternate method, not using the cyclic patterns in gait, involved using two inertial sensors attached to the thigh and shank to estimate the acceleration sensor output at the center of the knee joint \[[@b11-sensors-14-23230],[@b12-sensors-14-23230]\]. This method obtained accurate knee joint measurements and Takeda *et al.* \[[@b13-sensors-14-23230]\] expanded a similar approach to estimate the positions of hip, knee and ankle joint in a three dimensional global coordinate system. Though the hip and knee joint flexion-extension motions showed high correlation with a reference camera system, the internal-external rotation motion was not considered.
Recently, three dimensional wearable sensors systems have been made commercially available, such as the MTx (Xsens Technologies B.V., Enschede, The Netherlands). These sensor systems combine geomagnetic sensors to correct the orientation deviation of angular velocity and acceleration data. This allowed the calculation of internal and external rotation. High reliability and accuracy was reported using these systems for gait analysis \[[@b14-sensors-14-23230]\]. However, Brodie *et al.* \[[@b15-sensors-14-23230]\] reported that three dimensional orientation accuracy errors existed, even during static states, when compared to a camera based analysis. These sensor systems required periodic recalibration and ferromagnetic materials in the environment affected measurement accuracy.
In this work gait analysis of five healthy volunteers was measured using a wearable sensor gait analysis system called H-Gait (Development Code, Laboratory of Biomechanical Design, Hokkaido University, Sapporo, Japan) \[[@b8-sensors-14-23230],[@b13-sensors-14-23230],[@b16-sensors-14-23230]\]. The H-Gait system did not rely on an external magnetic field for reference and measurements were solely collected from orthogonally aligned tri-axial acceleration sensors and tri-axial gyro sensors which were fixed to seven locations on the lower limbs of each volunteer. The acceleration and angular velocity during level walking were collected. These measured data were then converted to three dimensional orientations of the wearable sensors, as well as the body segments they were attached to, using the H-Gait system\'s quaternion based algorithm developed by Tadano *et al.* \[[@b16-sensors-14-23230]\].
The H-Gait system was developed and intended to be used in evaluating the walking ability and rehabilitation effects of patients with gait disorders. Normally in clinical practice 10 m walking tests are conducted for the evaluation of patients with gait irregularities related to stroke, spinal cord injuries (SCI), osteoarthritis (OA), multiple sclerosis (MS), *etc.* \[[@b17-sensors-14-23230]--[@b19-sensors-14-23230]\]. Unfortunately, very little has been reported where wearable sensors have been used in 10 m walking tests that provided both three dimensional kinematics and spatio-temporal gait parameters. Therefore the objective of this work was to implement the H-Gait system to the 10 m walking test and provide clinicians with kinematic and spatio-temporal gait parameters required for diagnosing a patient. However, before this some issues with the drift error caused by angular velocity integration had to be addressed. In order to reduce the error caused by signal drift, this work implemented several novel countermeasures. These novel methods include, a sensor attachment calibration protocol, designing a Butterworth filter, removing sensor offset values and a double derivative and integration method. By implementing these countermeasures the signal drift was significantly reduced. As a result, the proposed method could provide the lower limb joint kinematics such as the hip/knee/ankle flexion-extension (FE) angles, hip/knee adduction-abduction (AA) angles, and hip/knee/ankle internal-external (IE) rotation angles. Moreover, a moving wire frame model was created to visually confirm the gait motion. In addition, spatio-temporal parameters such as gait cycle (GC), cadence (CD), step length (SL), step width (SW), stride (STRL), limp index (LI), stand ratio (STR) and swing ratio (SWR) were calculated from the heel-contact (HC) and toe-off (TO) timing of the foot.
2.. Method
==========
The objective of this work was to develop a method based on wearable sensors that can accurately and quantitatively detect abnormalities during walking. A customized gait analysis set-up and measurements protocol, including the subject preparation, the initial acquisition and the following walking trials, were properly planned.
2.1.. Drift Removal Countermeasures for Wearable Sensors
--------------------------------------------------------
The gait posture can be calculated by finding the gravitational acceleration direction from the acceleration sensor and calculated the initial three dimensional orientation of the body segment to which the sensor was attached. The subsequent three dimensional orientations from the initial one can be estimated by integrating the angular velocity measured by the gyro sensors. However, one of the difficulties involved in this method is error caused by the accumulation of signal noise during this integration process. The integrated values will deviate from the true value, thus causing drift. The countermeasures taken to reduce the effect of signal drift will explained in the following.
2.2.. Signal Noise Countermeasures
----------------------------------
### 2.2.1.. Sensor Attachment Errors Reduction Protocol
A calibration procedure for decreasing the attachment errors of the sensors to the body segments was implemented. [Figure 1](#f1-sensors-14-23230){ref-type="fig"} shows the three dimensional wire frame model implemented from the works of Tadano *et al.* \[[@b16-sensors-14-23230]\]. The wire frame model is created using orientations of each body segment and the volunteer specific body measurements. The calibration method obtained the rotation matrix for converting the sensor to body segment coordinate system. This procedure involved two simple steps of measuring the gravitational acceleration vector for each lower limb segment in two different postures, standing and sitting. The wearable sensors were assumed to be aligned in a 2-D sagittal plane and a rotation matrix was derived to convert measurements of the sensor coordinate system to the global coordinate system. This implementation lead to minimizing the effects of attachment errors associated with wearable sensors.
### 2.2.2.. Digital Filtering Protocol
An infinite impulse response (IIR) digital 4th order Butterworth filter was implemented to remove noise from the raw gyro sensor data. This low pass filter was implemented using MATLAB (Mathworks, Natick, MA, USA), where the cutoff frequency was set to 12 Hz chosen according to the Nyquist theorem. The filter was applied in both the forward and backward direction to cancel out phase lag caused by the Butterworth filter.
In addition to this, offset values from the gyro sensor data were removed. This was done by obtaining the mode value of the gyro sensor data at a static state and subtracting it from the measured data for each individual axis of each sensor unit.
Concerning what was reported in previous works \[[@b16-sensors-14-23230]\], the drift was not completely removed. Even for a measurement time of 14 s, drift appeared and influenced the final outcomes in terms of both joint kinematics and the wire frame model position and orientation in the space. While the previous method just attempted to remove the drift by subtracting from the entire signal the difference between the first and the last value of each angle of orientation of the sensor unit (roll, pitch and yaw), a more mathematically robust technique is here proposed, always assuming that the drift error linearly increases over time.
Based on this assumption, a double derivative and integration (DDI) method was implemented. Once the orientation angle *θ~out_i~(t)* of a sensor, along each *i* axis (x, y and z), was obtained, the true angle *θ~i~(t)* and the error *e~i~(t)* can be assumed as follows: $$\theta_{\textit{out\_i}}(t) = \theta_{i}(t) + e_{i}(t)$$
After a double derivative operation, the quantity e*~i~(t)* can be removed. Assuming that the drift error linearly increasing over time, once derived it becomes a constant (*const*) that if derived again can be neglected, according to [Equations (2)](#FD2){ref-type="disp-formula"} and [(3)](#FD3){ref-type="disp-formula"}: $$\frac{d(\theta_{\textit{out\_i}}(t))}{dt} = \frac{d(\theta_{i}(t))}{dt} + \frac{d(e_{i}(t))}{dt}$$ $$\frac{d^{2}(\theta_{\textit{out\_i}}(t))}{dt^{2}} = \frac{d^{2}(\theta_{i}(t))}{dt^{2}} + \frac{d(\textit{const})}{dt}$$
Considering that the orientation data is always necessary for the following analysis, a double integration was computed. This entails the addition of a constant of integration (c1 and c2), properly removed at each step of computation, as follows: $$\int{{\overset{¨}{\theta}}_{i}(t)dt = {\overset{˙}{\theta}}_{i}(t) + c1}$$ $$\int{{\overset{˙}{\theta}}_{i}(t)dt = \theta_{i}(t) + c2}$$
The integration constant *c*1 was considered as the initial angular velocity. Since this study considered the start of any gait trial as a static state (stance phase), the initial angular velocity was 0. In addition, the integration constant *c*2 was considered as the initial orientation. Therefore the initial orientation calculated from the acceleration sensors at a static state (stance phase) was inputted into *c*2.
[Figure 2](#f2-sensors-14-23230){ref-type="fig"} shows the simulation of the process for [Equations (2)](#FD2){ref-type="disp-formula"}--[(5)](#FD5){ref-type="disp-formula"}. The grey broken line represents the original signal (true value) and the red line represents the signal model with linear drift noise (original signal + drift noise). First, the original signal + drift noise is put through the double derivative process of [Equations (2)](#FD2){ref-type="disp-formula"} and [(3)](#FD3){ref-type="disp-formula"}, the result is the orange line. Then the integration is implemented by [Equation (4)](#FD4){ref-type="disp-formula"} and the initial angular velocity (in this case 0) is added as the integration constant (blue line). Finally, the double integration is completed by implementing [Equation (5)](#FD5){ref-type="disp-formula"} and adding the initial orientation of the sensor as the integration constant (green line). The simulation shows that the signal after the DDI process (green line) coincides with the original signal (grey line). This is because the underlining assumption is that the drift included in the original signal increases linearly with time. Therefore the DDI method is able to eliminate the accumulation of drift. The drift error was removed according to both the signal processing used for noise and bias reduction of gyro sensors data and to the methodology aforementioned.
2.3.. Gait Parameters: Spatio-Temporal Analysis and Joint Kinematics
--------------------------------------------------------------------
Gait is usually defined in terms of temporal and spatial components, indicating the timing periods during which the gait events occur and both the position and orientation of limbs and joints in the space, respectively. A gait cycle is commonly divided into the stance and the swing phase; the first one starts with an initial foot contact, namely heel-contact (HC), while the second one starts with a toe-off (TO) event. Based on these main timing events, spatio-temporal gait parameters, such as GC, CD, SL, SW, STRL, LI, STR, SWR occurring during a gait cycle \[[@b1-sensors-14-23230],[@b20-sensors-14-23230]\] can be derived.
In this study, the spatio-temporal parameters and gait phases were considered, as listed in [Table 1](#t1-sensors-14-23230){ref-type="table"}, starting from the identification of both HC and TO timing events for each foot. It has been reported elsewhere that the HC and TO timings can be detected by accelerometers on the shank \[[@b21-sensors-14-23230]\]. In this work these timing events were automatically identified directly from the angular velocity recorded from sensors placed on both shanks, with a MATLAB algorithm.
As shown in [Figure 3](#f3-sensors-14-23230){ref-type="fig"}, the HC are detected by the characteristic lateral angular velocity peaks and the TO timings are detected by measuring the negative peaks of the relative distance of the toe position to the origin of the pelvis (PE) coordinate system. Based on proper peaks of the angular velocity along the lateral axes of each segment, the gait cycles and stand ratio were calculated. The cadence, stride length, step length and step width were calculated by measuring the HC position of both legs. [Figure 4](#f4-sensors-14-23230){ref-type="fig"} shows the relationship between the global coordinate system used in this work and the new local foot coordinate system created for each step. Each body segment is indicated as follows: pelvis (PE), right and left thigh (RT, LT), right and left shank (RS, LS), right and left foot (RF, LF). If the right foot (RF) is on the ground, during the HC to foot flat (FF), local foot coordinate system *x~local~*, *y~local~*, and *z~local~* are created from the heel position of RF. From FF until the HC of left foot (LF), local foot coordinate system *x~local~*, *y~local~*, and *z~local~* are created from the toe position of RF. The other body segment three dimensional orientations in the global coordinate system are calculated based on their relative orientation against RF. Therefore, the body segment three dimensional orientations in the global coordinate system will be calculated in the order of RF→RS→RT→PE→LT→LS→LF. This order will continue until LF is on the ground where a new local foot coordinate system *x′~local~*, *y′~local~*, and *z′~local~* is created and the orientation calculation order will start from LF→LS→LT→PE→RT→RS→RF.
Joint kinematics in terms of gait trends are commonly analyzed during a clinical gait analysis session. In this work, joint kinematic gait parameters such as the hip/knee/ankle flexion-extension (FE) angles, hip/knee adduction-abduction (AA) angles, and hip/knee/ankle internal-external (IE) rotation angles can be calculated.
3.. Experiments
===============
Experiments were conducted indoors on a straight flat floor with five healthy volunteers. The volunteers\' body measurements were taken before experiment and are shown in [Table 2](#t2-sensors-14-23230){ref-type="table"}. Body measurements such as the distance of the greater trochanter (GT) to the lateral condyle of tibia (LCT), LCT to ankle joint, ankle joint height and the right GT to left GT width. For calculation simplification purposes the body measurements of the healthy subjects were assumed to be bilaterally symmetric and only the body measurements of the right limb were measured.
The volunteers\' were asked to do one gait trial consisting of standing still, 10 m walking test and then to standing still again. The volunteers wore spandex tracksuit pants with seven small pockets, for each body segment, fitted to hold the H-Gait system\'s wearable sensor units. Reflective markers were placed on 10 anatomical characteristic positions of the lower limb and a still picture was taken from the front and the two sides ([Figure 1](#f1-sensors-14-23230){ref-type="fig"}). The walking distance was approximately 10 m, equivalent to 10 steps (5 steps for each right and left leg).
4.. Results
===========
The comparison of the joint angle results obtained through the different methods of signal drift reduction protocol (raw data, IIR + offset removal, IIR + offset removal + DDI), for each lower limb joint (hip joint flexion angle, knee joint flexion angle and ankle joint flexion angle) are shown in [Figure 5](#f5-sensors-14-23230){ref-type="fig"}.
The results are an example of a volunteer over a period of 10 s of walking. The raw data, represented by the dotted line, is the joint angle calculated without implementing any of the signal drift protocols, thus the effect of error is large. During about 1.4--7.8 s, while the volunteer was performing the gait motion, the drift increased linearly. This is the reason why DDI method was a plausible method to remove this linear drift effect during dynamic states such as gait. The IIR + offset removal protocol, represented by the broken line, refers to the method proposed by Tadano *et al.* \[[@b16-sensors-14-23230]\]. The IIR + offset removal + DDI protocol, represented by the solid line, represents the results from this work.
[Figures 6](#f6-sensors-14-23230){ref-type="fig"} and [7](#f7-sensors-14-23230){ref-type="fig"} represent the trajectories of the right GT and left GT, knee joint center and ankle joint center in the sagittal *Z~global~*-*X~global~* plane respectively. Both [Figures 6](#f6-sensors-14-23230){ref-type="fig"} and [7](#f7-sensors-14-23230){ref-type="fig"} are plotted at a sampling rate of 33 Hz. The trajectories for the knee joint center and ankle joint center trajectories projected on the horizontal *X~global~*-*Y~global~* plane are shown in [Figure 8](#f8-sensors-14-23230){ref-type="fig"}. Both sagittal and horizontal trajectories results are that of three gait cycles of each subject plotted at 33 Hz. [Table 3](#t3-sensors-14-23230){ref-type="table"} shows the result of the spatio-temporal parameters for each subject. Here the gait cycle, cadence, step length, step width, stride length, limp index, stand ratio and swing ratio are shown.
5.. Discussion and Conclusions
==============================
The objective of this work was to propose a method for removing the effect of drift for improving the measurement accuracy of gait using wearable sensors. The results show that implementation of a combination of countermeasures; sensor attachment errors reduction protocol, IIR digital 4th order Butterworth filter, offset removal and the DDI method, were successful in reducing the effect of signal drift.
The results from [Figure 5](#f5-sensors-14-23230){ref-type="fig"} show differences in the joint angles after about 10 s of gait. The average difference for all 5 volunteers, after 10 s, were 2.1°, 33.3° and 15.6° for the hip, knee and ankle joint angles, respectively, when comparing between RAW and IIR + offset removal + DDI. In addition, the difference between implementing IIR + offset removal and IIR + offset removal + DDI was 6.2°, 6.6° and 2.2° for the hip, knee and ankle joint angles, respectively. This shows that the proposed countermeasure allowed for an average of 17° of drift error removal compared to integrating raw angular velocity data and an average of 5° less drift error than previous reported methods \[[@b16-sensors-14-23230]\].
The results of [Figures 6](#f6-sensors-14-23230){ref-type="fig"} and [7](#f7-sensors-14-23230){ref-type="fig"} show that this method is able to visually compare the differences in the joint trajectories between the right GT and left GT, knee and ankle joint centers using the wire frame model in the sagittal plane. These kinematic gait parameters will allow the comparison of the flexion-extension angles of the knee during different timings of the gait cycle. [Figure 8](#f8-sensors-14-23230){ref-type="fig"} allowed for the comparison of the knee and ankle joint center relative trajectories in the horizontal plane. This data can compare the bilateral symmetry of both right and left knee joint and ankle joint trajectories. In addition the spatio-temporal parameters provided in [Table 3](#t3-sensors-14-23230){ref-type="table"} allow us to quantify the differences in the gait events between the right and left side. By combining both the kinematic and statio-temporal parameter, we can detect differences in gait of the left and right lower limb and see how the differences affect the orientation of body segments and ultimately the joint positions during gait.
The method reported here proved the feasibility of three dimensional gait analysis with the wearable sensor gait analysis system H-Gait in detecting gait events providing both kinematic and spatio-temporal parameters. However, the methodology introduced here is not exclusive to the H-Gait system and can be applied to other commercial wearable sensors systems using acceleration and gyro sensors. These data will be useful in clinical sites, such as those for the follow-up diagnosis after TKA, by using the gait parameters in order to quantify the recovery of walking \[[@b22-sensors-14-23230],[@b23-sensors-14-23230]\] or on the influence of a specific implants designs on gait \[[@b24-sensors-14-23230]\].
A limitation of this work lies in the sensor attachment error calibration procedure. This procedure assumed that the orientation change in the stand and sitting posture of the wearable sensors changed in the 2-D sagittal plane only. However if other motions, such as internal-external or varus-valgus rotations of the knee, were to take place in between the two postures, this would cause error in the results. Therefore fixing the knee joint more securely to insure that the internal-external and varus-valgus rotation does not interfere with the calibration maybe required. Another method would be to introduce another posture other than stand and sitting to consider the 3-D attachment error. Both possibilities will be investigated in future works.
The methodology reported here has implemented a mathematical technique for the drift reduction, in addition to the previous work \[[@b16-sensors-14-23230]\]. It was always assumed that drift linearly increased over time, taking into account that measurements were limited to about 10 s of gait. Elsewhere it has been reported that for long measurement times such as over 100 s the drift effect may not linearly increase \[[@b25-sensors-14-23230],[@b26-sensors-14-23230]\]. Therefore, for longer distances applications, a more robust method like the Kalman filters or empirical mode decomposition (EMD) techniques may have to be considered to effectively remove drift.
Recently, fusing tri-axial gyroscope and tri-axial acceleration data from an IMU via an optimized Kalman filter was proposed by Mazza *et al.* \[[@b27-sensors-14-23230]\]. The RMSE between the proposed method and an optical tracking system were less than 1.0°. Yuan and Chen developed a method, using a combination of an acceleration tuning algorithm and a Kalman filter, to remove drift from 3 IMUs \[[@b28-sensors-14-23230]\]. They reported accuracy within 2% of the total walking length. However, one of the draw backs of designing a complicated Kalman filter is the requirement of fine tuning or optimizing the internal filter parameters to gain accurate estimates. In addition, these parameters will vary according to the kind of IMU used and the signal noise of the environment. Therefore, the specification of the IMU, the surrounding noise level and the target motion must be understood to before designing a good Kalman filter. Bonnet *et al.*, introduced a method not requiring tuning by implementing an EMD technique \[[@b29-sensors-14-23230]\]. Though the result RMSE between the proposed method and an optical tracking system was less than 2.1°, it was more robust than using a Kalman filter.
The work presented here has not been compared against a reference optical motion tracking system. A comparison would have been useful to provide a more detailed confirmation surrounding the effectiveness of the proposed method. However, the comparison with an optical tracking system has already been discussed in previous studies \[[@b16-sensors-14-23230]\] and even without a detailed accuracy comparison, it has been reported that simple two dimensional IMU measurements were capable of providing kinematic and spatio-temporal gait parameters for comparing the paretic and non-paretic leg of a stroke patient \[[@b30-sensors-14-23230]\].
In conclusion, it can be said the methodology required to remove the drift effect depends on the wearable sensors used, the kind and distance of the gait measured. As stated in the introduction, this work intended the use of wearable sensors in measuring the normal 10 m walking test of patients. In most cases these patients have a hard time of even walking 10 m and asking them to walk even more is not practical. Therefore with the target walking distance limited to about 10 m, the proposed method here sufficiently reduces the effect of drift and allows a fairly accurate gait analysis of patients.
Following this study, other gait phases and parameters should be calculated and investigated more in the future, in order to analyze e.g., also other gait events, like the foot-flat phase in addition to the heel-contact and toe-off ones. Concerning the methodology used to manage the drift problem, a nonlinear assumption could be considered for future works.
The authors would like to acknowledge the Hokkaido University Hospital for assistance in the gait experiments.
Giulia Lisco: Experimental measurements and data analysis and the Methods section of this paper; Tadashi Fujisawa: Experimental measurements, data analysis and the Results section of this paper; Laura Gastaldi: Expertise in the motion analysis interpretation of the analyzed data and the Discussion section of this paper; Harukazu Tohyama: Expertise in the clinical evaluation interpretation of the analyzed results and the Discussion section of this paper; Shigeru Tadano: Supervision of the whole research project of the gait analysis using wearable sensors. Editing of the entire paper.
The authors declare no conflict of interest.
![Sensor attachment location and gait wire frame model. The wire frame model is created by connecting characteristic positions of the lower limb. Sensor units are attached to seven body segments of the lower limb. This model has been implemented from the works of Tadano *et al.* \[[@b16-sensors-14-23230]\].](sensors-14-23230f1){#f1-sensors-14-23230}
{#f2-sensors-14-23230}
{#f3-sensors-14-23230}
{#f4-sensors-14-23230}
######
Comparison of the joint angle results obtained through the different methods of signal drift reduction protocol (raw data, IIR + offset removal, IIR + offset removal + DDI) for a volunteer. (**a**) Hip joint flexion angle; (**b**) knee joint flexion angle and (**c**) ankle joint flexion angle are shown.
{#f6-sensors-14-23230}
{#f7-sensors-14-23230}
{#f8-sensors-14-23230}
######
The spatio-temporal gait parameters defined in this work.
**Parameter** **Definition**
---------------------- -------------------------------------------------------------
Gait cycle \[s\] Duration of a gait cycle
Cadence \[step/min\] Number of steps/min
Step length \[cm\] Distance between a heel-strike (or toe-off) of both feet
Step width \[cm\] Distance between medial lines of feet
Stride \[cm\] Distance between two heel-strikes (or toe-offs) of one foot
Limp Index Ratio of stance of subject limb *vs.* opposite limb
Stand ratio \[%\] Period of a gait cycle in which the foot is on the ground.
Swing ratio \[%\] Period of a gait cycle in which the foot is off the ground.
######
Information of the volunteers A to E. Body segment measurements between each characteristic anatomical point are used. The lengths are those measured from the right limb only.
**GT to LCT \[cm\]** **LCT to Ankle \[cm\]** **Ankle Height \[cm\]** **Right GT to Left GT Width \[cm\]**
--------- ---------------------- ------------------------- ------------------------- -------------------------------------- ------
Subject A 40.8 43.0 8.9 35.0
B 39.4 41.5 9.5 34.3
C 42.5 42.7 8.5 35.8
D 36.0 37.8 11.5 34.0
E 37.0 39.0 11.0 36.0
######
Spatio-temporal gait parameters for each subject (A, B, C, D, E) for both right and left lower limb. Gait cycle, cadence, step length, step width, stride length, limp index, stand ratio and swing ratio are shown with mean and standard deviation.
**A** **B** **C** **D** **E** **Mean** **SD**
---------------------- -------------------- ------------ -------- -------- -------- ---------- -------- ------ ------
Global Gait cycle \[sec\] 1.20 1.18 1.27 1.16 1.18 1.20 0.04
Cadence \[step/min\] 99.79 101.76 94.30 103.52 102.06 100.29 2.94
Step length \[cm\] 76.17 80.39 76.19 74.44 69.56 75.35 3.19
Step width \[cm\] 15.73 16.36 21.56 19.63 20.45 18.75 2.10
Stride \[cm\] 151.58 155.18 149.80 148.60 139.62 148.96 4.72
Differentiated Right Limp index 0.98 0.88 1.08 0.97 1.00 0.98 0.06
Stand ratio \[%\] 39.66 42.62 31.27 40.11 47.37 40.21 4.78
Swing ratio \[%\] 60.34 57.38 68.73 59.89 52.63 59.79 4.78
Left Limp index 1.02 1.14 0.92 1.03 1.00 1.02 0.06
Stand ratio \[%\] 40.15 41.91 36.69 42.43 43.37 40.91 2.15
Swing ratio \[%\] 59.85 58.09 63.31 57.57 56.63 59.09 2.15
[^1]: External Editor: Panicos Kyriacou
| |
The following is a speech (as prepared) for the immigration working group of the Intergovernmental Consultations on Migration, Asylum and Refugees on Wednesday, November 17, 2021.
______
Greetings, my name is Esther Brimmer, and I serve as the executive director and CEO of NAFSA: Association of International Educators, the world’s leading organization committed to international education and exchange. Together with the more than 10,000 members and international educators that we serve worldwide, we work to advance policies and practices that build global citizens with the knowledge and skills they need to succeed in today's interconnected world.
It will be my pleasure today to offer you a perspective on just how the world benefits from international education and exchange, how the COVID pandemic has both negatively impacted our field and been the source of real innovation, and to discuss how countries, including the United States, can advance global learning and exchange by adopting a coordinated, proactive national strategy for international education.
Let me begin by establishing why we do the work we do. At NAFSA, we share with our practitioners at colleges and universities around the world, a deep and abiding core belief in the power of a peaceful, equitable, and globally connected world.
It drives all that we do. It is what compels us to advocate so strongly for the presence of international students and scholars in U.S. classrooms, and communities, and to increase and diversify the number of U.S. students that participate in study abroad experiences.
It provides the inspiration for our NAFSA RISE Scholarships which seek to bring underrepresented communities into the profession, and our steady pursuit of U.S. federal legislation that would make both the study abroad destinations, and the demographics of the students who participate, more diverse.
The value of having a globally engaged and diverse campus, and a culturally competent student body, has real practical ramifications for our civil society, economy and global competitiveness, too. Our research shows, for example, that employers and job seekers alike recognize that skills developed during study abroad are essential for management and leadership positions.
And one need look no further than the extraordinary research and development success of the highly effective COVID vaccines to see how very valuable it is to create pathways for the world’s global talent to collaborate. Some of the leaders at the forefront of the Moderna and Pfizer-BioNTech vaccines began their careers as international students in the U.S. and Europe, and the full roster of scientists involved includes countries all over the globe, illustrating just how powerful it is to draw from the world’s best and brightest.
Obviously, no discussion of global student mobility can take place without fully appreciating the impact that the COVID pandemic has had on our field and the lessons that it has taught us in resilience, adaptation, and innovation.
The initial phase of the coronavirus public health crisis and the declaration of a global pandemic in March 2020 halted the flow of students across borders, and brought education abroad programs to a standstill.
The U.S. response to the pandemic in March 2020 significantly impacted international student enrollment, as U.S. universities and colleges quickly shifted to online education and had most of their students disperse from on-campus housing for the rest of the academic year.
Some students would return home, including international students returning to their home country.
Initially, the U.S. put in place COVID-related travel restrictions affecting individuals coming from China, but the list of countries with these restrictions eventually grew to a total of 33.
The pandemic also significantly impacted almost all in-person U.S. study abroad programming. In September 2020, NAFSA conducted a survey of senior leadership. We found that:
- Nearly 87% of respondents with study abroad programs did not send any U.S. students abroad for Fall 2020, resulting in an estimated $700 million in financial losses across U.S. higher education.
- About 38% responded that staff positions had or would be impacted by cancelled study abroad programs.
During the next phase of the pandemic – the 2020-2021 academic year (US/North America)– higher education continued to experience significant restrictions on mobility, severely impacting enrollments and associated economic benefits. In the United States, data released two days ago show dramatic declines in the number and economic contributions of international students during this time period.
- According to this year’s Open Doors report, an annual report published by the Institute of International Education in partnership with the U.S. State Department, 914,095 international students studied in the United States during the 2020-2021 academic year. This is down 15% from the prior academic year, largely to due to the pandemic.
- NAFSA’s latest annual analysis of the economic contributions of international students and their families to the U.S. economy shows that international students studying in the U.S. during this same time period contributed $28.4 billion to the U.S. economy. This is down 26.6% from the prior year.
More broadly, the move to online virtual instruction, and the physical isolation that resulted, created significant and unanticipated financial, social, logistical, academic, and mental health-related consequences for institutions and their students.
- The dramatic shift to a virtual learning environment presented real challenges to institutions’ engagement with students, and despite innovative support services and programming, high levels of mental health distress among international students were reported.
- On the academic side, varying time zones and asynchronous learning have not been conducive to class discussions, requiring students to be more proactive.
But through this time period, the COVID pandemic also served as a true mother of invention, and provided fertile ground for sudden and bold innovation.
- The pandemic changed the recruitment landscape, prompting a greater reliance on the use of technology to conduct recruitment activities from virtual fairs to virtual campus tours.
- The new realities created opportunities in international recruitment: Technology enabled institutions to cast a wider net and reach students in countries where they did not have a presence. It allowed institutions to reach a greater diversity of regions and countries than they had previously.
- The pandemic also forced institutions to engage in virtual learning platforms in novel and groundbreaking ways, expanding their collaboration with stakeholders focused on online learning.
- International alumni also played a vital role, helping many institutions by serving as a local resource for students when travel was not allowed.
The pandemic also sparked greater collaboration among key stakeholders on campuses who focus on diversity, equity and inclusion (DEI).
- Reduced resources brought the DEI and IE communities together to explore the intersections of their work and the communities they serve.
- New program models offer increased access for students from diverse backgrounds who may not otherwise engage in an international experience during their academic career.
When the pandemic hit in March 2020, education abroad professionals confronted a new reality. With campuses largely closed for months and study abroad opportunities scarce, education abroad offices had to quickly adopt virtual approaches for everything from recruitment and orientation to advising and internships.
The rapid and unprecedented introduction of virtual options in study abroad programs may have started from necessity, but a new hybrid environment of in-person and virtual components is poised to last.
However, we are seeing encouraging signs on the international student enrollment front and the resumption of study abroad programs, largely attributable to the advent of highly effective COVID vaccines, and a change in leadership in the United States. This 2021-2022 academic year marked the beginning of a new phase in the pandemic.
Results of a snapshot survey conducted by the Institute of International Education released two days ago indicate that international student enrollment at U.S. colleges and universities this autumn, 2021, is recovering from last autumn’s significant decline.
According to the results:
- U.S. higher ed institutions report a 68 percent increase in the number of new international students enrolling (up significantly from the 46 percent decline reported for fall 2020).
- The overall number of international students enrolling increased by 4 percent. This is up from the 15 percent decrease reported in fall 2020.
- At least 65 percent of the reported international students are on campus in the U.S. (up from 47 percent last fall).
Another encouraging sign is the removal of the COVID-related travel restrictions affecting 33 countries on November 8th, replacing it with a full vaccine requirement that applies to all international travelers. This is welcome news.
The new policy includes an exception to the full vaccine requirement for international travelers from countries where vaccine availability is very limited, allowing them to receive the vaccine in the U.S. after arrival.
NAFSA joined with other U.S. higher education organizations in advocating for allowing the entry for international students and scholars traveling from countries with limited vaccine availability and to receive the vaccine after arrival. Having this new policy in place now is very helpful as colleges and universities plan for the spring academic term.
As for study abroad, we hope to see an increase as travel continues to open up and students who have been postponing their plans are finally able to study abroad. Some U.S. institutions have been sending students abroad to carefully vetted locations since the spring of this year, 2021 – most of those will continue to do so for the 2021-2022 academic year.
Other institutions were making plans to resume study abroad and student travel, but were disrupted by the resurgence of COVID-19 and new variants. In August this year, the European Union recommended that countries again restrict travel for unvaccinated Americans. While these countries are some of the more popular study abroad destinations, it is unlikely to have a negative effect because American students have access to the COVID-19 vaccine. Now we see that more institutions are eager to return to travel during the 2021-2022 academic year.
What can nations do to fully emerge from the COVID winter, and cultivate these inspiring examples of new growth and positive trends?
Establishing whole-of-government approaches to the development and implementation of a comprehensive national strategy for international education provides countries with great advantage when seeking to increase international recruitment. Let me unpack exactly what I mean by that.
First of all, the creation of a national strategy and associated policies to guide the recruitment and retention of international students relies on a country’s commitment to an international recruitment goal or target.
In a related fashion, many tactics can be employed, and policies changed to aid a country in meeting established recruitment goals, but this will be best achieved if the nation employs a whole-of-government approach in their efforts. Here I mean that while control over international education policy may fall under the purview of various co-equal ministries or federal agencies (as is the case in the United States), there must be a mechanism in place to allow for coordination across sometimes competing interests and to ensure leaders remain aligned in seeking to reach the nation’s stated international recruitment goals.
As I earlier suggested, national strategies have already been employed by several countries around the world to great positive effect prior to the COVID pandemic. Allow me to go into some detail here because I think it is important to making the case:
Let’s start with Canada.
- In 2014, Canada announced an international education strategy seeking to attract 450,000 international students by 2022. It adopted friendly international student policies, including expedited visa processing for certain qualifying students. Canada also offers post-study work visas that can last up to three years and has made it easier for international students to immigrate.
- As a result, Canada’s international student enrollment increased by more than 80 percent in the five years prior to the pandemic, making the country one of the world’s fastest-growing study destinations during that period. In 2019, it hosted 642,000 international students, surpassing the initial target.
- However, like other nations, the pandemic has been impactful for Canada; recent data show the number of international students with study permits for Canada declined by 17% in 2020. In response, the Canadian government moved to allow access to post-study work for students completing online study during the pandemic, to help stem further declines.
Turning to the United Kingdom, in March 2019, the UK government announced an international education strategy, with the goal of hosting 600,000 international students by the year 2030.
- In September 2019, the government also moved to reinstate a two-year post-study work visa for graduates starting in the 2020 –21 academic year, recognizing that opportunities for post-study work experience is key to attracting international students.
- In January 2020, the UK government announced a new, fast-track visa program to attract the world’s top scientists, researchers and mathematicians. As part of its Research and Development roadmap, in July 2020, the UK government announced the establishment of an “Office of Talent” which will work to ensure immigration policies are welcoming to global research talent.
- In October 2020, the government announced a new immigration pathway for international students and graduates based on the UK’s new points-based immigration system; as of July 1, this year, international students who successfully complete a degree are allowed to stay in the UK for two years, and for three years if a PhD graduate.
- These initiatives are having an impact despite the COVID pandemic. In 2020, international enrollment at UK universities increased by 12 percent, and the total number of international students in the country exceeded 500,000 for the first time, well on the way to meeting their target.
Australia also has favorable international student policies, such as permitting students to work for up to 18 months after graduation; with graduates of certain high-need occupations allowed to work longer, up to four years.
- However, with the onset of the global pandemic in March 2020, Australia closed its borders to all non-citizens and non-residents; as a result, international student enrollments plummeted, dropping 54% from October 2019 to October 2021.
- Australia plans to reopen its borders to international students by December this year. As many competitor countries did not close their borders completely to international students, Australia recognizes it will need to be proactive in attracting back students kept out of the country due to COVID-19.
Finally, let’s consider China. The United States has traditionally viewed China as a “source or sending” country of international students to the United States. However, China has rapidly become a major host country.
- As far back as 2008, China set a target of bringing half a million foreign students to its shores by 2020; prior to COVID-19, China was on track to meet this goal, hosting 492,000 students in 2019.
- In 2014, China quietly surpassed the United Kingdom and the United States as a top destination for international students from Africa—and it continues to draw increasing numbers of students from the continent.
- China’s place as a top destination for African international students is the product of a concerted effort. According to data from China's Ministry of Education, as of 2018, the number of African students in China exceeded 80,000.
- In January 2017, China announced new regulations allowing international students graduating with a master’s degree or above to immediately apply for work visas within one year of graduation.
- However, like Australia, China closed its borders in early 2020 due to the pandemic, and they will likely remain closed into early 2022, with limited exceptions, barring thousands of international students from returning to China to continue their studies.
Comparatively, the United States lacks a coordinated U.S. government-led international education strategy. The rationale for implementing one will take up the remainder of my remarks.
On July 26 this year, the U.S. Departments of State and Education released a Joint Statement of Principles for international education that renews focus on the role of international education in improving U.S. diplomacy, global competitiveness, and higher education, as well as the lives of the American people.
The countries that I described above can turn to their already existing national strategies and policies to attract and retain international students and to even expand their reach in the aftereffects of the pandemic. There is a friendly global competition for talent, and even before the pandemic, the U.S. was losing market share for international students—despite the tireless efforts of colleges and universities.
What we are therefore urging the Biden Administration to adopt is a national strategy that establishes targets, policies, and funds programs to:
- increase the number and diversity of international students at U.S. higher education institutions;
- increase the number and diversity of American students participating in study abroad programs; and
- promote efforts to internationalize U.S. campuses.
In order to prioritize and institute a whole-of-government approach to international education, the United States should establish a White House Coordinating Council on International Education. Because international education policy falls under the jurisdiction of more than one federal agency, this requires a coordinating entity within the White House to ensure collaboration and compromise within and across key federal agencies that results in more welcoming visa and immigration policies for international students and scholars, as well as more robust programs and resources to help grow and diversify U.S. study abroad participation and enhance U.S. campus internationalization.
The Council should be charged with establishing recruitment goals for international talent. The strategy should set targets for international student enrollment with an emphasis on increasing diversity of source countries and of students’ socioeconomic background.
Any approach to enhance access to international education must also include a strategy to help grow and diversify U.S. college student participation in study abroad. With less than 10 percent of U.S. college students ultimately graduating with a study abroad experience on their transcript, that means 90 percent of graduates are entering the workforce without the global skills, knowledge, and experiences that would position them for success in the global economy.
Finally, the nation must internationalize U.S. campuses using innovative means.
And with that, I will conclude with the hope that you all may bring to your home countries both a renewed appreciation for the vital role international education can play in fostering a more equitable and peaceful world and a better understanding of the tools available to facilitate its growth and impact.
We at NAFSA stand ready as a resource for the world--offering research, best practices, and policy recommendations--to ensure that international education may evolve and flourish as a means to advance learning and scholarship and cultivate respect among diverse backgrounds and perspectives.
The COVID pandemic was indeed a serious blow to our field and global academic mobility as a whole, yet it provided a unique stage to showcase the life-saving power of ingenuity and what can be achieved when we work together.
I believe nations will emerge strengthened in this next phase of the pandemic by establishing a renewed commitment to recruiting international talent bolstered by a whole-of-government approach.
I look forward to writing the next chapter for international education with global leaders like you. | https://www.nafsa.org/blog/whole-government-approach-implementing-national-strategy-international-education |
Course overview:
Our MA Games Design covers both advanced theoretical and practical strands ensuring you are fully literate in areas such as complex gameplay design, project management, advanced mission design, gameplay implementation and the utilisation of advanced technologies such as Virtual Reality. You develop key transferable skills such as advanced presentation skills and are encouraged to creatively experiment with ways of conveying concepts and information.
The first semester enables you to use advanced research methods in relation to game design, allowing you to pursue a career in games research or to prepare for advanced study in MPhil or Doctorate programmes. You gain advanced practical skills required for complex mission design and implementation, as well as the ability to create advanced gameplay scenarios and professional design documents. The second semester enables you to tackle complex game development scenarios and apply advanced game management techniques, ensuring projects are organised in a professional manner from pre-production, through production, delivery and project closure. You also have an opportunity to develop – in interdisciplinary teams – a small prototype using a contemporary game engine and a prototype utilising advanced virtual reality technologies in a fully equipped VR studio.
The final semester involves the master’s project and dissertation. This is a large 60 credit module where you can design and develop a large project based on research. It has been designed to allow you to further develop and display the advanced skills and knowledge you have acquired over the programme.
How you learn:
You learn about concepts and methods primarily through keynote lectures and tutorials using case studies and examples. Lectures include presentations from guest speakers from industry. Critical reflection is key to successful problem solving and essential to the creative process. You develop your own reflective practice at an advanced level, then test and assess your solutions against criteria that you develop in the light of your research.
How you are assessed:
The programme assessment strategy has been designed to assess your subject specific knowledge, cognitive and intellectual skills and transferable skills applicable to the workplace. The strategy ensures that you are provided with formative assessment opportunities throughout the programme which support your summative assessments. There is a mix of practical work (usually in the form of a portfolio), poster and viva presentations, written reports. Formative feedback is typically given during lectures, tutorials and summative feedback using on-line methods. The assessments can include individual or group work. The assessment criteria, where appropriate, will include assessment of presentation skills and report writing.
Career opportunities:
We prepare you for a career in industry. In addition to your taught classes, we create opportunities for you to meet and network with our industry partners through events such as our ExpoSeries, which showcases student work to industry. ExpoTees is the pinnacle of the ExpoSeries with over 100 businesses from across the UK coming to the campus to meet our exceptional students, with a view to recruitment.
Full time
2 years
21-SEP-20
For this course (per year)
£4,335
Average for all Postgrad courses (per year)
£5,202
For this course (per year)
£7,500
Average for all Postgrad courses (per year)
£12,227
Applicants will normally have a first degree in related discipline (2.2 minimum) or relevant experience or equivalent qualifications. | https://www.postgraduatesearch.com/teesside-university-middlesbrough/57451272/postgraduate-course.htm |
Steve Jobs Dies: 3 Inventors Who Revolutionized Communications
When Steve Jobs died on Wednesday, the world lost not only one of its greatest inventors, but one of the few people in history to truly revolutionize the way the world communicates.
There are countless scientists and technologists whose work paved the way for communication as we know it: from Alexander Graham Bell, who invented the telephone, to Vladimir Zworykin, who designed a television with cathode-ray tubes, to Thomas Edison, who had the idea to make electricity available to the public.
But true innovation isn't just about creating a new means of communication. Where people like Steve Jobs stand alone is in creating a new conception of communication: in fundamentally changing the way we view our relationship with one another and with the world.
Here are the three people who did the most for communication. | http://www.ibtimes.com/steve-jobs-dies-3-inventors-who-revolutionized-communications-552888 |
Situated in the Island of Panay and joins such wonderful places like Iloilo, Capiz and Antique, and though not as popular as the attractions within, it is recognized as the most recommended and top destination for travel and leisure activities by all travel agents locally and internationally. The province boasts of 2 major attractions such as the world famous Boracay Island and the famed Ati-atihan that are both considered as one of the eight wonders of tourism. The Province of Aklan is also considered as one or at least the oldest province of the Philippines giving it a rich history and culture, since the arrival of the datus to Panay but only acquired its status as a province on April 25, 1956 signed by President Ramon Magsaysay separating it from the Province of Capiz. At present it is designated as a second class province with 17 Municipalities that comprises it namely, Altavas, Balete, Banga, Batan, Buruanga, Ibajay, Kalibo, Lezo, Libacao, Madalag, Makato, Malay, Malinao, Nabas, New Washington, Numancia, and Tangalan with Kalibo as its capital
Since it is a top destination, reaching Aklan from Manila or from other parts of the country is easy. By air it has 2 airports with Caticlan Airport or Godofredo P. Ramos and the Kalibo Airport. The Caticlan Airport is quite new and provides sophisticated facilities that caters mostly to domestic flights while the Kalibo Airport is classified as a minor domestic class with a few international flights. A few of the airline companies that service the province are Air Philippines, Asian Spirit, Cebu Pacific, Philippine Airlines, South East Asian Airlines, Pacific Pearl Airways and the China Eastern Airlines. Traveling by land from Manila the Philtranco Bus Company is the only means of transport that provides service with a daily scheduled service. By sea there are a few ferry companies that service the province and 2 of which are the major shipping lines that service the province, MBRS Shipping Lines and Negros Navigation respectively.
The province’s top destination is Boracay, which is situated in the Municipality of Malay, and has 2 popular beaches namely the White Beach and Bulabog Beach. Resorts or places of accommodation are abundant to satisfy both local and international visitors with pricing based on peak and low seasons. Other leisure activities are hiking, diving, snorkeling, sightseeing kite boarding and wind surfing. Festival attractions in Aklan is the most sought after. The internationally knowned Kalibo Ati-Atihan Festival is celebrated annually on the month of January in honor of the Santo Nino spanning from the first Sunday and concluding up to the third Sunday. It is the most colorful noise making festival of all with the constant beating of the drums and whistle blowing participants clad in dry leaves, faces painted and bodies colored with soot while the Bariw Festival which is celebrated in the Month of May from the 12th to the 15th is of similar celebration with participants dressed in Bariw Leaves, contionous dancing in the streets participated by 20 barangays of the province.
Places of stay are sufficient in Aklan. To visit the province for a holiday of fun and adventure or a mere relaxation, Wow Paradise Philippines recommends to book yourself in advance. Though there are quite a number of resort, hotels and other accommodations most are booked all year round. For more information visit the Province of Aklan Official Website and see for yourself the beauty within. | http://www.wowparadisephilippines.com/aklan-the-beauty-within.html |
TECHNICAL FIELD
BACKGROUND
SUMMARY
BRIEF DESCRIPTION OF DRAWINGS
DESCRIPTION OF EMBODIMENTS
Embodiments of the present invention relate to communications technologies, and in particular, to a device and a method for data transmission in D2D communication.
If wireless communication coverage is relatively good, both an operator and a government wish that some public safety events could be handled by wireless communication. After a safety event occurs, an immediate commanding team and a rescue team perform communication in a certain geographic area. Each team member holds a special terminal. This special terminal is referred to as a device to device (Device to Device, D2D for short) communications device or a cellular terminal D2D communications device. That is, like an ordinary wireless terminal, this terminal can perform cellular communication with a base station, and can also directly communicate with another cellular D2D communications terminal. Due to blocking of a terrain and a time-varying feature of radio signals, there is actually a cell coverage hole. In public safety requirements, it is required that a cellular D2D communications terminal can be applied within network coverage and without network coverage. Generally, public safety personnel are multiple persons that are grouped or clustered to take actions.
In conventional long term evolution (Long Term Evolution, LTE for short), an asynchronous retransmission hybrid automatic repeat request (Hybrid Automatic Repeat Request, HARQ for short) mode is used for transmitting downlink data, and a synchronous retransmission mode is used for uplink data.
However, if an LTE retransmission mode is used in D2D communication, because there is no feedback channel between transmitting user equipment (User Equipment, UE for short) and receiving UE, the LTE retransmission mode cannot be used to ensure reliability of data transmission.
Embodiments of the present invention provide a device and a method for data transmission in D2D communication, which are used to implement reliable data transmission in D2D communication.
a transmission module, configured to transmit scheduling signaling to receiving user equipment (UE), where the scheduling signaling includes at least one of frequency domain resource information, a quantity of cycles that can be occupied, or transmission pattern information; and
a processing module, configured to transmit user data to the receiving UE according to the scheduling signaling, so that the receiving UE receives the user data according to the scheduling signaling.
A first aspect of the present invention provides transmitting user equipment, including:
repeatedly transmit the user data to the receiving UE according to the scheduling signaling, according to a transmission pattern indicated by the transmission pattern information, and according to the quantity of times of repeated transmission of the data packet, in a frequency domain position indicated by the frequency domain resource information, in a transmission subframe indicated by the quantity of cycles that can be occupied.
In a first possible implementation manner of the first aspect, the scheduling signaling further includes a quantity of times of repeated transmission of a data packet; and
the processing module is specifically configured to:
control an automatic repeat request HARQ process of the transmitting UE to: obtain a first PDU in a medium access control packet data unit MAC PDU buffer, and record a quantity of times of transmission as 0; and if the HARQ process determines, according to an identifier of the HARQ process and the transmission pattern, that a transmission subframe of the first PDU arrives, transmit the first PDU to the receiving UE by using the transmission subframe of the first PDU, and add 1 to the quantity of times of transmission, until the quantity of times of transmission reaches the quantity of times of repeated transmission of the data packet.
According to the first possible implementation manner of the first aspect, in a second possible implementation manner of the first aspect, the processing module is further configured to:
According to the second possible implementation manner of the first aspect, in a third possible implementation manner of the first aspect, if a resource corresponding to a first HARQ process is allocated to another transmitting UE for use, the processing module stops using the first HARQ process after the quantity of times of transmission reaches the quantity of times of repeated transmission of the data packet.
control a MAC PDU buffer of the transmitting UE to transmit a second PDU to an HARQ process of the transmitting UE, and record a quantity of times of transmission as 1, so that when the HARQ process determines that a transmission subframe of the first PDU arrives, the HARQ process transmits the second PDU to the receiving UE by using the transmission subframe of the second PDU; and when the MAC PDU buffer determines, according to the transmission pattern, that a minimum repetition interval expires, transmit the second PDU to the HARQ process again, until the quantity of times of transmission reaches the quantity of times of repeated transmission of the data packet, where the second PDU includes an identifier of the transmitting HARQ process.
According to the first possible implementation manner of the first aspect, in a fourth possible implementation manner of the first aspect, the processing module is further configured to:
According to the first aspect, in a fifth possible implementation manner of the first aspect, the scheduling signaling further includes an indication that a data packet is new data, where the indication that the data packet is new data is used to indicate that the user data to be transmitted by the transmitting UE is new data.
With reference to the first aspect or any one of the first to fifth possible implementation manners of the first aspect, in a sixth possible implementation manner of the first aspect, the scheduling signaling further includes identifier information of the transmitting UE, where the identifier information is used to indicate a priority of using a frequency domain resource by the transmitting UE.
With reference to the first aspect or any one of the first to sixth possible implementation manners of the first aspect, in a seventh possible implementation manner of the first aspect, the scheduling signaling further includes a service type of the user data to be transmitted by the transmitting UE.
before the transmission module transmits the scheduling signaling to the receiving UE, generate the scheduling signaling; or
before the transmission module transmits the scheduling signaling to the receiving UE, receive the scheduling signaling transmitted by a base station.
With reference to the first aspect or any one of the first to seventh possible implementation manners of the first aspect, in an eighth possible implementation manner of the first aspect, the processing module is further configured to:
a receiving module, configured to receive scheduling signaling transmitted by transmitting user equipment (UE), where the scheduling signaling includes at least one of frequency domain resource information, a quantity of cycles that can be occupied, or transmission pattern information; and
a processing module, configured to receive, according to the scheduling signaling received by the receiving module, user data transmitted by the transmitting UE.
A second aspect of the present invention provides receiving user equipment, including:
repeatedly receive, according to the scheduling signaling received by the receiving module, according to a transmission pattern indicated by the transmission pattern information, and according to the quantity of times of repeated transmission of the data packet, in a frequency domain position indicated by the frequency domain resource information, in a transmission subframe indicated by the quantity of cycles that can be occupied, the user data repeatedly transmitted by the transmitting UE.
In a first possible implementation manner of the second aspect, the scheduling signaling further includes a quantity of times of repeated transmission of a data packet; and
the processing module is specifically configured to:
transmit, according to the transmission pattern information, first user data in a first subframe in a first frame to a second automatic repeat request HARQ process corresponding to the first subframe, and transmit, according to the transmission pattern information, second user data in a second subframe in a second frame to a third HARQ process corresponding to the second subframe.
According to the first possible implementation manner of the second aspect, in a second possible implementation manner of the second aspect, the processing module is further configured to:
receive, according to the scheduling signaling received by the receiving module and according to a transmission pattern indicated by the transmission pattern information, in a frequency domain position indicated by the frequency domain resource information, in a transmission subframe indicated by the quantity of cycles that can be occupied, the new user data transmitted by the transmitting UE.
According to the second aspect, in a third possible implementation manner of the second aspect, the scheduling signaling further includes an indication that a data packet is new data, where the indication that the data packet is new data is used to indicate that the user data to be transmitted by the transmitting UE is new data; and
the processing module is further configured to:
create, according to the service type, a radio link control (RLC) entity corresponding to the service type; and
configure parameters of the RLC entity according to a configuration table that is in configuration tables prestored in the receiving UE and corresponds to the service type.
With reference to the second aspect or any one of the first to third possible implementation manners of the second aspect, in a fourth possible implementation manner of the second aspect, the scheduling signaling further includes a service type of the user data to be transmitted by the transmitting UE; and
the processing module is further configured to:
the transmitter is configured to transmit scheduling signaling to receiving user equipment (UE), where the scheduling signaling includes at least one of frequency domain resource information, a quantity of cycles that can be occupied, or transmission pattern information; and
the processor is configured to transmit user data to the receiving UE according to the scheduling signaling, so that the receiving UE receives the user data according to the scheduling signaling.
A third aspect of the present invention provides transmitting user equipment, including a transmitter, a receiver, a memory, and a processor that is connected to the transmitter, the receiver, and the memory, where:
repeatedly transmit the user data to the receiving UE according to the scheduling signaling, according to a transmission pattern indicated by the transmission pattern information, and according to the quantity of times of repeated transmission of the data packet, in a frequency domain position indicated by the frequency domain resource information, in a transmission subframe indicated by the quantity of cycles that can be occupied.
In a first possible implementation manner of the third aspect, the scheduling signaling further includes a quantity of times of repeated transmission of a data packet; and
the processor is specifically configured to:
control an automatic repeat request HARQ process of the transmitting UE to: obtain a first PDU in a medium access control packet data unit MAC PDU buffer, and record a quantity of times of transmission as 0; and if the HARQ process determines, according to an identifier of the HARQ process and the transmission pattern, that a transmission subframe of the first PDU arrives, transmit the first PDU to the receiving UE by using the transmission subframe of the first PDU, and add 1 to the quantity of times of transmission, until the quantity of times of transmission reaches the quantity of times of repeated transmission of the data packet.
According to the first possible implementation manner of the third aspect, in a second possible implementation manner of the third aspect, the processor is further configured to:
According to the second possible implementation manner of the third aspect, in a third possible implementation manner of the third aspect, if a resource corresponding to a first HARQ process is allocated to another transmitting UE for use, the processor stops using the first HARQ process after the quantity of times of transmission reaches the quantity of times of repeated transmission of the data packet.
control a MAC PDU buffer of the transmitting UE to: transmit a second PDU to an HARQ process of the transmitting UE, and record a quantity of times of transmission as 1, so that when the HARQ process determines that a transmission subframe of the first PDU arrives, the HARQ process transmits the second PDU to the receiving UE by using the transmission subframe of the second PDU; and when the MAC PDU buffer determines, according to the transmission pattern, that a minimum repetition interval expires, transmit the second PDU to the HARQ process again, until the quantity of times of transmission reaches the quantity of times of repeated transmission of the data packet, where the second PDU includes an identifier of the transmitting HARQ process.
According to the first possible implementation manner of the third aspect, in a fourth possible implementation manner of the third aspect, the processor is further configured to:
According to the third aspect, in a fifth possible implementation manner of the third aspect, the scheduling signaling further includes an indication that a data packet is new data, where the indication that the data packet is new data is used to indicate that the user data to be transmitted by the transmitting UE is new data.
With reference to the third aspect or any one of the first to fifth possible implementation manners of the third aspect, in a sixth possible implementation manner of the third aspect, the scheduling signaling further includes identifier information of the transmitting UE, where the identifier information is used to indicate a priority of using a frequency domain resource by the transmitting UE.
With reference to the third aspect or any one of the first to sixth possible implementation manners of the third aspect, in a seventh possible implementation manner of the third aspect, the scheduling signaling further includes a service type of the user data to be transmitted by the transmitting UE.
before the transmitter transmits the scheduling signaling to the receiving UE, generate the scheduling signaling; or
before the transmitter transmits the scheduling signaling to the receiving UE, receive the scheduling signaling transmitted by a base station.
With reference to the third aspect or any one of the first to seventh possible implementation manners of the third aspect, in an eighth possible implementation manner of the third aspect, the processor is further configured to:
the receiver is configured to receive scheduling signaling transmitted by transmitting user equipment (UE), where the scheduling signaling includes at least one of frequency domain resource information, a quantity of cycles that can be occupied, or transmission pattern information; and
the processor is configured to receive, according to the scheduling signaling received by the receiver, user data transmitted by the transmitting UE.
A fourth aspect of the present invention provides receiving user equipment, including a transmitter, a receiver, a memory, and a processor that is connected to the transmitter, the receiver, and the memory, where:
repeatedly receive, according to the scheduling signaling received by the receiver, according to a transmission pattern indicated by the transmission pattern information, and according to the quantity of times of repeated transmission of the data packet, in a frequency domain position indicated by the frequency domain resource information, in a transmission subframe indicated by the quantity of cycles that can be occupied, the user data repeatedly transmitted by the transmitting UE.
In a first possible implementation manner of the fourth aspect, the scheduling signaling further includes a quantity of times of repeated transmission of a data packet; and
the processor is specifically configured to:
transmit, according to the transmission pattern information, first user data in a first subframe in a first frame to a second automatic repeat request HARQ process corresponding to the first subframe, and transmit, according to the transmission pattern information, second user data in a second subframe in a second frame to a third HARQ process corresponding to the second subframe.
According to the first possible implementation manner of the fourth aspect, in a second possible implementation manner of the fourth aspect, the processor is further configured to:
receive, according to the scheduling signaling received by the receiver and according to a transmission pattern indicated by the transmission pattern information, in a frequency domain position indicated by the frequency domain resource information, in a transmission subframe indicated by the quantity of cycles that can be occupied, the new user data transmitted by the transmitting UE.
According to the fourth aspect, in a third possible implementation manner of the fourth aspect, the scheduling signaling further includes an indication that a data packet is new data, where the indication that the data packet is new data is used to indicate that the user data to be transmitted by the transmitting UE is new data; and
the processor is further configured to:
create, according to the service type, a radio link control (RLC) entity corresponding to the service type; and
configure parameters of the RLC entity according to a configuration table that is in configuration tables prestored in the receiving UE and corresponds to the service type.
With reference to the fourth aspect or any one of the first to third possible implementation manners of the fourth aspect, in a fourth possible implementation manner of the fourth aspect, the scheduling signaling further includes a service type of the user data to be transmitted by the transmitting UE; and
the processor is further configured to:
transmitting, by transmitting user equipment (UE), scheduling signaling to receiving UE, where the scheduling signaling includes at least one of frequency domain resource information, a quantity of cycles that can be occupied, or transmission pattern information; and
transmitting, by the transmitting UE, user data to the receiving UE according to the scheduling signaling, so that the receiving UE receives the user data according to the scheduling signaling.
A fifth aspect of the present invention provides a method for data transmission in D2D communication, where the method includes:
repeatedly transmitting, by the transmitting UE, the user data to the receiving UE according to the scheduling signaling, according to a transmission pattern indicated by the transmission pattern information, and according to the quantity of times of repeated transmission of the data packet, in a frequency domain position indicated by the frequency domain resource information, in a transmission subframe indicated by the quantity of cycles that can be occupied.
In a first possible implementation manner of the fifth aspect, the scheduling signaling further includes a quantity of times of repeated transmission of a data packet; and
the transmitting, by the transmitting UE, user data to the receiving UE according to the scheduling signaling, includes:
obtaining, by an automatic repeat request HARQ process of the transmitting UE, a first PDU in a medium access control packet data unit MAC PDU buffer, and recording a quantity of times of transmission as 0; and
if the HARQ process of the transmitting UE determines, according to an identifier of the HARQ process and the transmission pattern, that a transmission subframe of the first PDU arrives, transmitting the first PDU to the receiving UE by using the transmission subframe of the first PDU, and adding 1 to the quantity of times of transmission, until the quantity of times of transmission reaches the quantity of times of repeated transmission of the data packet.
According to the first possible implementation manner of the fifth aspect, in a second possible implementation manner of the fifth aspect, the repeatedly transmitting, by the transmitting UE, the user data to the receiving UE according to the scheduling signaling, according to a transmission pattern indicated by the transmission pattern information, and according to the quantity of times of repeated transmission of the data packet, in a frequency domain position indicated by the frequency domain resource information, in a transmission subframe indicated by the quantity of cycles that can be occupied, includes:
According to the second possible implementation manner of the fifth aspect, in a third possible implementation manner of the fifth aspect, if a resource corresponding to a first HARQ process is allocated to another transmitting UE for use, the transmitting UE stops using the first HARQ process after the quantity of times of transmission reaches the quantity of times of repeated transmission of the data packet.
transmitting, by a MAC PDU buffer of the transmitting UE, a second PDU to an HARQ process of the transmitting UE, and recording a quantity of times of transmission as 1, so that when the HARQ process determines that a transmission subframe of the first PDU arrives, the HARQ process transmits the second PDU to the receiving UE by using the transmission subframe of the second PDU; and
when the MAC PDU buffer of the transmitting UE determines, according to the transmission pattern, that a minimum repetition interval expires, transmitting the second PDU to the HARQ process again, until the quantity of times of transmission reaches the quantity of times of repeated transmission of the data packet, where the second PDU includes an identifier of the transmitting HARQ process.
According to the first possible implementation manner of the fifth aspect, in a fourth possible implementation manner of the fifth aspect, the repeatedly transmitting, by the transmitting UE, the user data to the receiving UE according to the scheduling signaling, according to a transmission pattern indicated by the transmission pattern information, and according to the quantity of times of repeated transmission of the data packet, in a frequency domain position indicated by the frequency domain resource information, in a transmission subframe indicated by the quantity of cycles that can be occupied, includes:
According to the fifth aspect, in a fifth possible implementation manner of the fifth aspect, the scheduling signaling further includes an indication that a data packet is new data, where the indication that the data packet is new data is used to indicate that the user data to be transmitted by the transmitting UE is new data.
With reference to the fifth aspect or any one of the first to fifth possible implementation manners of the fifth aspect, in a sixth possible implementation manner of the fifth aspect, the scheduling signaling further includes identifier information of the transmitting UE, where the identifier information is used to indicate a priority of using a frequency domain resource by the transmitting UE.
With reference to the fifth aspect or any one of the first to sixth possible implementation manners of the fifth aspect, in a seventh possible implementation manner of the fifth aspect, the scheduling signaling further includes a service type of the user data to be transmitted by the transmitting UE.
generating, by the transmitting UE, the scheduling signaling; or
receiving, by the transmitting UE, the scheduling signaling transmitted by a base station.
With reference to the fifth aspect or any one of the first to seventh possible implementation manners of the fifth aspect, in an eighth possible implementation manner of the fifth aspect, before the transmitting, by the transmitting UE, scheduling signaling to receiving UE, the method further includes:
receiving, by receiving user equipment (UE), scheduling signaling transmitted by transmitting UE, where the scheduling signaling includes at least one of frequency domain resource information, a quantity of cycles that can be occupied, or transmission pattern information; and
receiving, by the receiving UE according to the scheduling signaling, user data transmitted by the transmitting UE.
A sixth aspect of the present invention provides a method for data transmission in D2D communication, where the method includes:
repeatedly receiving, by the receiving UE according to the scheduling signaling, according to a transmission pattern indicated by the transmission pattern information, and according to the quantity of times of repeated transmission of the data packet, in a frequency domain position indicated by the frequency domain resource information, in a transmission subframe indicated by the quantity of cycles that can be occupied, the user data repeatedly transmitted by the transmitting UE.
In a first possible implementation manner of the sixth aspect, the scheduling signaling further includes a quantity of times of repeated transmission of a data packet; and
the receiving and processing, by the receiving UE according to the scheduling signaling, user data transmitted by the transmitting UE, includes:
transmitting, by the receiving UE according to the transmission pattern information, first user data in a first subframe in a first frame to a second automatic repeat request HARQ process corresponding to the first subframe, and transmitting, by the receiving UE according to the transmission pattern information, second user data in a second subframe in a second frame to a third HARQ process corresponding to the second subframe.
According to the first possible implementation manner of the sixth aspect, in a second possible implementation manner of the sixth aspect, the receiving, by the receiving UE according to the scheduling signaling, according to a transmission pattern indicated by the transmission pattern information, and according to the quantity of times of repeated transmission of the data packet, in a frequency domain position indicated by the frequency domain resource information, in a transmission subframe indicated by the quantity of cycles that can be occupied, the user data repeatedly transmitted by the transmitting UE, includes:
receiving, by the receiving UE according to the scheduling signaling and according to a transmission pattern indicated by the transmission pattern information, in a frequency domain position indicated by the frequency domain resource information, in a transmission subframe indicated by the quantity of cycles that can be occupied, the new user data transmitted by the transmitting UE.
According to the sixth aspect, in a third possible implementation manner of the sixth aspect, the scheduling signaling further includes an indication that a data packet is new data, where the indication that the data packet is new data is used to indicate that the user data to be transmitted by the transmitting UE is new data; and
the receiving and processing, by the receiving UE according to the scheduling signaling, user data transmitted by the transmitting UE, includes:
creating, by the receiving UE according to the service type, a radio link control RLC entity corresponding to the service type; and
configuring, by the receiving UE, parameters of the RLC entity according to a configuration table that is in configuration tables prestored in the receiving UE and corresponds to the service type.
With reference to the sixth aspect or any one of the first to third possible implementation manners of the sixth aspect, in a fourth possible implementation manner of the sixth aspect, the scheduling signaling further includes a service type of the user data to be transmitted by the transmitting UE; and
the method further includes:
In the device and method for data transmission in D2D communication that are provided by the embodiments, a transmission module transmits scheduling signaling to the receiving UE, where the scheduling signaling includes at least one of frequency domain resource information, a quantity of cycles that can be occupied, or transmission pattern information; and a processing module transmits user data to the receiving UE according to the scheduling signaling, so that the receiving UE receives the user data according to the scheduling signaling. Therefore, if there is no feedback from the receiving UE in a D2D communication process, the transmitting UE can repeatedly transmit the user data, and the receiving UE can repeatedly receive the user data and perform combination processing on the received repeated data, thereby improving reliability of data transmission.
FIG. 1
is a schematic structural diagram of Embodiment 1 of transmitting user equipment according to the present invention;
FIG. 2
is a schematic diagram of a transmission pattern in scheduling signaling;
FIG. 3
is a schematic diagram of UE;
FIG. 4
is a schematic diagram of a correspondence between a transmission subframe number and an HARQ process identifier;
FIG. 5
is a schematic structural diagram of Embodiment 2 of transmitting user equipment according to the present invention;
FIG. 6
is a schematic structural diagram of Embodiment 1 of receiving user equipment according to the present invention;
FIG. 7
is a schematic structural diagram of Embodiment 2 of receiving user equipment according to the present invention;
FIG. 8
is a flowchart of Embodiment 1 of a method for data transmission in D2D communication according to the present invention;
FIG. 9
is a flowchart of Embodiment 2 of a method for data transmission in D2D communication according to the present invention; and
FIG. 10
is a flowchart of Embodiment 3 of a method for data transmission in D2D communication according to the present invention.
To describe the technical solutions in the embodiments of the present invention or in the prior art more clearly, the following briefly describes the accompanying drawings required for describing the embodiments or the prior art. Apparently, the accompanying drawings in the following description show some embodiments of the present invention, and a person of ordinary skill in the art may still derive other drawings from these accompanying drawings without creative efforts.
To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the following clearly and completely describes the technical solutions in the embodiments of the present invention with reference to the accompanying drawings in the embodiments of the present invention. Apparently, the described embodiments are some but not all of the embodiments of the present invention. All other embodiments obtained by a person of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.
FIG. 1
FIG. 1
is a schematic structural diagram of Embodiment 1 of transmitting user equipment according to the present invention. As shown in , the transmitting user equipment in this embodiment includes a transmission module 11 and a processing module 12. The transmission module 11 is configured to transmit scheduling signaling to receiving UE, where the scheduling signaling includes at least one of frequency domain resource information, a quantity of cycles that can be occupied, or transmission pattern information. The processing module 12 is configured to transmit user data to the receiving UE according to the scheduling signaling, so that the receiving UE receives the user data according to the scheduling signaling.
Specifically, the frequency domain resource information in the scheduling information in this embodiment may include a frequency domain resource index or a maximum frequency domain resource range. If only one user transmits data at a same transmission time, the frequency domain resource information may be a maximum frequency domain resource range. If multiple users transmit data at a same transmission time, the frequency domain resource information is a frequency domain resource index, and the quantity of cycles that can be occupied is used to indicate a quantity of cycles that can be occupied by the user data transmitted by the transmitting UE.
FIG. 2
FIG. 2
FIG. 2
is a schematic diagram of a transmission pattern in the scheduling signaling. The transmission pattern information may include time that can be occupied by the transmitting UE in a cycle and a repetition mode of a data packet. As shown in , UE A may occupy the first and the third milliseconds for transmission in every eight milliseconds. The repetition mode of the data packet may include an immediate repetition, that is, a same data packet may be transmitted in the first and third milliseconds, or a discontinuous repetition and a minimum repetition interval, that is, after being transmitted, a data packet can be transmitted repeatedly only after waiting for a period of time. For example, in , a piece of data is transmitted in the first millisecond, and the data packet can be transmitted again only after waiting for 8 ms or a longer time.
Specifically, the scheduling signaling in this embodiment may include at least one of the frequency domain resource information, the quantity of cycles that can be occupied, and the transmission pattern information. If only one or two of the information are included, the other two or one of the information is fixed.
For example, in a scenario in which the scheduling signaling in this embodiment includes only the frequency domain resource information, the transmission pattern information and the quantity of cycles that can be occupied are fixed. In a scenario in which the scheduling signaling in this embodiment includes only the quantity of cycles that can be occupied, the frequency domain resource information and the transmission pattern information are fixed. It may be specified that a fixed correspondence exists between a frequency domain position occupied by the scheduling signaling and a frequency domain position occupied by the user data. For example, if the scheduling signaling is transmitted in a third symbol of every two physical resource blocks (Physical Resource Block, PRB for short), data information is transmitted in any symbol except the third symbol and a pilot symbol in the two PRBs. In a scenario in which the scheduling signaling in this embodiment includes only the transmission pattern information, the frequency domain resource information and the quantity of cycles that can be occupied are fixed.
The processing module 12 of the transmitting UE transmits the to-be-transmitted user data according to the frequency domain resource information, the quantity of cycles that can be occupied, and the transmission pattern information in the scheduling signaling, in a frequency domain resource position indicated by the frequency domain resource occupation information, in a transmission time subframe indicated by the quantity of cycles that can be occupied; and the receiving UE receives, according to the transmission pattern indicated by the transmission pattern information, in the frequency domain position indicated by the frequency domain resource information, in the transmission subframe indicated by the quantity of cycles that can be occupied, the user data transmitted by the transmitting UE.
According to the transmitting user equipment provided by this embodiment, repeated transmission of user data is determined by a processing module 12 of the transmitting UE according to scheduling signaling, and is not determined according to whether there is any feedback from receiving UE. Therefore, if there is no feedback from the receiving UE in a D2D communication process, the transmitting UE may repeatedly transmit the user data, and the receiving UE may repeatedly receive the user data and perform combination processing on the received repeated data, thereby improving reliability of data transmission.
In the transmitting user equipment provided by this embodiment, a transmission module 11 transmits scheduling signaling to receiving UE, where the scheduling signaling includes at least one of frequency domain resource information, a quantity of cycles that can be occupied, or transmission pattern information; and a processing module 12 transmits user data to the receiving UE according to the scheduling signaling, so that the receiving UE receives the user data according to the scheduling signaling. Therefore, if there is no feedback from the receiving UE in a D2D communication process, the transmitting UE may repeatedly transmit the user data, and the receiving UE may repeatedly receive the user data and perform combination processing on the received repeated data, thereby improving reliability of data transmission.
repeatedly transmit the user data to the receiving UE according to the scheduling signaling, according to a transmission pattern indicated by the transmission pattern information, and according to the quantity of times of repeated transmission of the data packet, in a frequency domain position indicated by the frequency domain resource information, in a transmission subframe indicated by the quantity of cycles that can be occupied.
In an embodiment, the scheduling signaling further includes a quantity of times of repeated transmission of a data packet; and
the processing module 12 is specifically configured to:
control an HARQ process of the transmitting UE to obtain a first PDU in a medium access control (Medium Access Control, MAC for short) packet data unit (Packet Data Unit, PDU for short) buffer, and record a quantity of times of transmission as 0; and if the HARQ process determines, according to an identifier of the HARQ process and the transmission pattern, that a transmission subframe of the first PDU arrives, transmit the first PDU to the receiving UE by using the transmission subframe of the first PDU, and add 1 to the quantity of times of transmission, until the quantity of times of transmission reaches the quantity of times of repeated transmission of the data packet.
In an embodiment, the processing module 12 is further configured to:
FIG. 3
FIG. 3
is a schematic diagram of UE. As shown in , a radio link control (Radio Link control, RLC for short) module and a MAC module exist in the UE. The MAC module includes a PDU buffer and an HARQ process. The HARQ process is configured to process functions of data transmission (including initial transmission and repeated transmission), data reception and combination check, and delivering data to the PDU buffer. A quantity of HARQ processes is defined according to a processing capability of the UE. In a cellular system, generally, it is considered that there are eight HARQ processes. In a multiple-input multiple-output system, there may be 16 HARQ processes. For a D2D group user, a case of coexistence of D2D communication and cellular communication may occur, or either of D2D communication and cellular communication may occur. For convenient and simple implementation of the UE, HARQ processes may be used by the cellular communication and the D2D communication jointly. That is, when there is only cellular communication, all the HARQ processes are occupied by cellular communication. When there is only D2D communication, all the HARQ processes are occupied by the D2D communication. When there are both D2D communication and cellular communication, they separately occupy some HARQ processes.
In this embodiment, it may be assumed that there is only D2D communication, and that all the HARQ processes may be occupied by the D2D communication.
When the UE is used as transmitting UE, for example, it is determined, according to the information in the scheduling signaling, that data may be transmitted in two time subframes, and therefore, the UE decides that two services, namely, one service represented by RLC 3 and another service represented by RLC 5, are both used to transmit data. Therefore, data packets of two services exist in the MAC PDU buffer, where quantities of times of repeated transmission of the data packets of the services may be the same or may be different. The following uses an example in which quantities of times of repeated transmission are the same, where RLC 3 represents a voice service, RLC 5 represents a picture transmission service, and maximum quantities of times of repeated transmission of the two services are both 4. Multiple data packets are separately generated in the two services, and transmitted to the MAC PDU buffer. An HARQ process fetches a new PDU from the MAC PDU buffer according to a transmission status of the HARQ process after a previous data packet is repeatedly transmitted for four times, and records a quantity of times of transmission as 0; after a transmission subframe of the UE arrives, the HARQ process transmits the new PDU, and changes the quantity of times of transmission Tx_NB to Tx_NB + 1 after transmission; when the quantity of times of transmission reaches an allowed maximum quantity of times of repeated transmission, namely, Tx_NB = 4, the HARQ process fetches new data from the MAC PDU buffer; after a MAC PDU is fetched by the HARQ process, the fetched MAC PDU is deleted from the MAC PDU buffer.
FIG. 4
FIG. 4
is a schematic diagram of a correspondence between a transmission subframe number and an HARQ process identifier. As shown in , a conversion relationship between a transmission subframe number and an HARQ process identifier is: (frame number * 10 + subframe number) mod 8 = 1&2. By using this formula, the HARQ process may calculate whether a next subframe is a subframe for transmitting data by the HARQ process. The calculation process may also be performed a longer time in advance. Data transmission is completed by a physical layer. The identifier of the HARQ process used in transmission is obtained through calculation according to the transmission pattern in the scheduling signaling. That is, the transmitting UE uses HARQ processes 1 and 2 to process transmission of MAC PDUs, and the receiving UE demodulates the received data and then transmits the data to a process whose HARQ process identifier is 1 or 2 for processing.
In an embodiment, if a resource corresponding to a first HARQ process is allocated to another transmitting UE for use, the processing module 12 stops using the first HARQ process after the quantity of times of transmission reaches the quantity of times of repeated transmission of the data packet.
For example, processing after the transmission pattern of the transmitting UE is changed is described in this embodiment. When UE B in a D2D group has service data of a higher priority for transmission, a transmission resource of UE A is preempted by UE B, and transmission resources of UE A are reduced. For example, in each frame, two subframes that may transmit data of UE A are reduced to only one subframe that may transmit data of UE A. Therefore, a case in which data in an HARQ process buffer cannot be transmitted again but a quantity of times of repeated transmission is not completed yet may occur, and this is because the HARQ process is associated with a transmission subframe number. To ensure reliable data transmission, UE A may not use the process any longer after continuing to repeatedly transmit the data in the HARQ process buffer for a remaining quantity of times. After obtaining information indicating that the resource may be used, UE B starts to use the resource after waiting for a period equal to a quantity of repetitions multiplied by a repetition interval.
In the transmitting user equipment provided by this embodiment, a transmission module 11 of the transmitting UE transmits scheduling signaling to receiving UE, where the scheduling signaling includes frequency domain resource information, a quantity of cycles that can be occupied, transmission pattern information, and a quantity of times of repeated transmission of a data packet; and a processing module 12 of the transmitting UE repeatedly transmits user data to the receiving UE according to the scheduling signaling, according to a transmission pattern indicated by the transmission pattern information, and according to the quantity of times of repeated transmission of the data packet, in a frequency domain position indicated by the frequency domain resource information, in a transmission subframe indicated by the quantity of cycles that can be occupied. Therefore, if there is no feedback from the receiving UE in a D2D communication process, the transmitting UE may repeatedly transmit the user data, and the receiving UE may repeatedly receive the user data and perform combination processing on the received repeated data, thereby improving reliability of data transmission.
control a MAC PDU buffer of the transmitting UE to: transmit a second PDU to an HARQ process of the transmitting UE, and record a quantity of times of transmission as 1, so that when the HARQ process determines that a transmission subframe of the first PDU arrives, the HARQ process transmits the second PDU to the receiving UE by using the transmission subframe of the second PDU; and when the MAC PDU buffer determines, according to the transmission pattern, that a minimum repetition interval expires, transmit the second PDU to the HARQ process again, until the quantity of times of transmission reaches the quantity of times of repeated transmission of the data packet, where the second PDU includes an identifier of the transmitting HARQ process.
In an embodiment, the processing module 12 is further configured to:
Specifically, after the HARQ process fetches data, the MAC PDU buffer of the transmitting end may continue to reserve the PDU, and change a counter Current_TX_NB to Current_TX_NB + 1. The HARQ process fetches data from a MAC PDU when performing transmission every time, and the MAC PDU buffer provides appropriate data to the HARQ process according to a transmission status and a repetition status of a PDU. For example, if the transmitting UE obtains transmission capabilities of two consecutive subframes in a frame, a first subframe transmits a MAC PDU 1, and a second subframe must transmit a MAC PDU 2 and cannot continue to transmit the MAC PDU 1, because the scheduling signaling requires that a repeated transmission interval of each packet should not be 0. Therefore, when the repeated transmission interval is satisfied, the MAC PDU buffer provides a repeated data packet to the HARQ process, and a case in which data packets transmitted at the first time and subsequently repeatedly transmitted use different subframe numbers may occur. In this case, the transmitting UE needs to notify, in the data packet, a process number used by the transmitting UE to the receiving end, so that the receiving UE can combine the received repeated data. After receiving a new data packet, the receiving UE demodulates the data packet into soft bits and then transmits the soft bits to an HARQ process buffer corresponding to the data packet, and after a repeated packet of the data packet arrives, also transmits soft bits to a corresponding HARQ process buffer according to a process number carried in the repeated packet and performs combination.
In the transmitting user equipment provided by this embodiment, a transmission module 11 of the transmitting UE transmits scheduling signaling to receiving UE, where the scheduling signaling includes frequency domain resource information, a quantity of cycles that can be occupied, transmission pattern information, and a quantity of times of repeated transmission of a data packet; and a processing module 12 of the transmitting UE repeatedly transmits user data to the receiving UE according to the scheduling signaling, according to a transmission pattern indicated by the transmission pattern information, and according to the quantity of times of repeated transmission of the data packet, in a frequency domain position indicated by the frequency domain resource information, in a transmission subframe indicated by the quantity of cycles that can be occupied. Therefore, if there is no feedback from the receiving UE in a D2D communication process, the transmitting UE may repeatedly transmit the user data, and the receiving UE may repeatedly receive the user data and perform combination processing on the received repeated data, thereby improving reliability of data transmission.
In an embodiment, the scheduling signaling further includes an indication that a data packet is new data, where the indication that the data packet is new data is used to indicate that the user data to be transmitted by the transmitting UE is new data.
Specifically, if the user data to be transmitted by the transmitting UE is new data, the scheduling signaling further includes the indication that the data packet is new data; if the user data to be transmitted by the transmitting UE is data that is transmitted repeatedly, the scheduling signaling does not include the indication that the data packet is new data.
In an embodiment, the scheduling signaling further includes identifier information of the transmitting UE, where the identifier information is used to indicate a priority of using a frequency domain resource by the transmitting UE.
Specifically, the identifier information of the UE may be a global identifier in a large area, or may be an intra-group identifier allocated by a group owner. The identifier information of the UE has a meaning indicating a priority. If another UE also uses a same resource, after the UE detects a collision, UE having smaller UE identifier information may preferentially use the resource.
In an embodiment, the scheduling signaling further includes a service type of the user data to be transmitted by the transmitting UE.
before the transmission module 11 transmits the scheduling signaling to the receiving UE, generate the scheduling signaling; or
before the transmission module 11 transmits the scheduling signaling to the receiving UE, receive the scheduling signaling transmitted by a base station.
In an embodiment, the processing module 12 is further configured to:
Specifically, the scheduling signaling transmitted by the transmission module 11 of the transmitting UE to the receiving UE may be generated by the transmitting UE, or may be received by the transmitting UE from the base station.
In the transmitting user equipment provided by this embodiment, a transmission module 11 of the transmitting UE transmits scheduling signaling to receiving UE, where the scheduling signaling includes frequency domain resource information, a quantity of cycles that can be occupied, or transmission pattern information; and a processing module 12 of the transmitting UE transmits user data to the receiving UE according to the scheduling signaling, so that the receiving UE receives the user data according to the scheduling signaling. Therefore, if there is no feedback from the receiving UE in a D2D communication process, the transmitting UE may repeatedly transmit the user data, and the receiving UE may repeatedly receive the user data and perform combination processing on the received repeated data, thereby improving reliability of data transmission.
FIG. 5
FIG. 5
is a schematic structural diagram of Embodiment 2 of transmitting user equipment according to the present invention. As shown in , the transmitting user equipment in this embodiment includes a transmitter 21, a receiver 22, a memory 23, and a processor 24 that is connected to the transmitter 21, the receiver 22, and the memory 23. Certainly, the user equipment may further include a universal component such as an antenna, a baseband processing unit, an intermediate radio frequency processing unit, or an input and output apparatus, which is not limited any longer in the embodiment of the present invention.
The transmitter 21 is configured to transmit scheduling signaling to receiving UE, where the scheduling signaling includes at least one of frequency domain resource information, a quantity of cycles that can be occupied, or transmission pattern information; and the processor 24 is configured to transmit user data to the receiving UE according to the scheduling signaling, so that the receiving UE receives the user data according to the scheduling signaling.
repeatedly transmit the user data to the receiving UE according to the scheduling signaling, according to a transmission pattern indicated by the transmission pattern information, and according to the quantity of times of repeated transmission of the data packet, in a frequency domain position indicated by the frequency domain resource information, in a transmission subframe indicated by the quantity of cycles that can be occupied.
In an embodiment, the scheduling signaling further includes a quantity of times of repeated transmission of a data packet; and
the processor 24 is specifically configured to:
control an automatic repeat request HARQ process of the transmitting UE to: obtain a first PDU in a medium access control packet data unit MAC PDU buffer, and record a quantity of times of transmission as 0; and if the HARQ process determines, according to an identifier of the HARQ process and the transmission pattern, that a transmission subframe of the first PDU arrives, transmit the first PDU to the receiving UE by using the transmission subframe of the first PDU, and add 1 to the quantity of times of transmission, until the quantity of times of transmission reaches the quantity of times of repeated transmission of the data packet.
In an embodiment, the processor 24 is further configured to:
In an embodiment, if a resource corresponding to a first HARQ process is allocated to another transmitting UE for use, the processor 24 stops using the first HARQ process after the quantity of times of transmission reaches the quantity of times of repeated transmission of the data packet.
control a MAC PDU buffer of the transmitting UE to: transmit a second PDU to an HARQ process of the transmitting UE, and record a quantity of times of transmission as 1, so that when the HARQ process determines that a transmission subframe of the first PDU arrives, the HARQ process transmits the second PDU to the receiving UE by using the transmission subframe of the second PDU; and when the MAC PDU buffer determines, according to the transmission pattern, that a minimum repetition interval expires, transmit the second PDU to the HARQ process again, until the quantity of times of transmission reaches the quantity of times of repeated transmission of the data packet, where the second PDU includes an identifier of the transmitting HARQ process.
In an embodiment, the processor 24 is further configured to:
In an embodiment, the scheduling signaling further includes an indication that a data packet is new data, where the indication that the data packet is new data is used to indicate that the user data to be transmitted by the transmitting UE is new data.
In an embodiment, the scheduling signaling further includes identifier information of the transmitting UE, where the identifier information is used to indicate a priority of using a frequency domain resource by the transmitting UE.
In an embodiment, the scheduling signaling further includes a service type of the user data to be transmitted by the transmitting UE.
before the transmitter 21 transmits the scheduling signaling to the receiving UE, generate the scheduling signaling; or
before the transmitter 21 transmits the scheduling signaling to the receiving UE, receive the scheduling signaling transmitted by a base station.
In an embodiment, the processor 24 is further configured to:
FIG. 1
The transmitting UE in this embodiment is an entity embodiment corresponding to the embodiment shown in , and their implementation principles and technical effects are similar, and are not further described herein.
FIG. 6
FIG. 6
is a schematic structural diagram of Embodiment 1 of receiving user equipment according to the present invention. As shown in , the receiving user equipment in this embodiment includes a receiving module 31 and a processing module 32. The receiving module 31 is configured to receive scheduling signaling transmitted by transmitting UE, where the scheduling signaling includes at least one of frequency domain resource information, a quantity of cycles that can be occupied, or transmission pattern information. The processing module 32 is configured to receive, according to the scheduling signaling received by the receiving module 31, user data transmitted by the transmitting UE.
According to the receiving user equipment provided by this embodiment, repeated transmission of user data is determined by transmitting UE, and is not determined according to whether there is any feedback from the receiving UE. Therefore, if there is no feedback from the receiving UE in a D2D communication process, the transmitting UE may repeatedly transmit the user data, and the receiving UE may repeatedly receive the user data and perform combination processing on the received repeated data, thereby improving reliability of data transmission.
In the receiving user equipment provided by this embodiment, a receiving module 31 receives scheduling signaling transmitted by transmitting UE, where the scheduling signaling includes at least one of frequency domain resource information, a quantity of cycles that can be occupied, or transmission pattern information; and a processing module 32 receives, according to the scheduling signaling received by the receiving module 31, user data transmitted by the transmitting UE. Therefore, if there is no feedback from the receiving UE in a D2D communication process, the transmitting UE may repeatedly transmit the user data, and the receiving UE may repeatedly receive the user data and perform combination processing on the received repeated data, thereby improving reliability of data transmission.
repeatedly receive, according to the scheduling signaling received by the receiving module 31, according to a transmission pattern indicated by the transmission pattern information, and according to the quantity of times of repeated transmission of the data packet, in a frequency domain position indicated by the frequency domain resource information, in a transmission subframe indicated by the quantity of cycles that can be occupied, the user data repeatedly transmitted by the transmitting UE.
In an embodiment, the scheduling signaling further includes a quantity of times of repeated transmission of a data packet; and
the processing module 32 is specifically configured to:
Specifically, the processing module 32 receives the data packet according to the frequency domain position and the transmission pattern that are included in the scheduling signaling received by the receiving module 31. Because the transmitting UE needs to perform repeated transmission for multiple times, the receiving UE needs to demodulate the repeatedly transmitted data at a physical layer and then transmit the data to a soft bit buffer for combination processing, and if a cyclic redundancy check (Cyclic Redundancy Check, CRC for short) check after combination is correct, deliver the data to an upper layer, or if a CRC check after combination is incorrect, continue to wait for a next repeated data packet, until a quantity of repetitions reaches a quantity of repetitions that is specified by the scheduling signaling. After the data is delivered to the upper layer or a maximum quantity of repetitions is reached or new data is received, the soft bit buffer is cleared.
transmit, according to the transmission pattern information, first user data in a first subframe in a first frame to a second automatic repeat request HARQ process corresponding to the first subframe, and transmit, according to the transmission pattern information, second user data in a second subframe in a second frame to a third HARQ process corresponding to the second subframe.
In an embodiment, the processing module 32 is further configured to:
FIG. 3
For example, still using a schematic diagram of UE shown in as an example to describe the receiving UE, the transmitting UE transmits, in a subframe 1 in a system frame number (System Frame Number, SFN for short) x, a MAC PDU 1 corresponding to an RLC 3 service, and transmits, in a subframe 2, a MAC PDU 2 corresponding to an RLC 5 service. Because five repetitions are required, when an SFN x + 1 arrives later, the MAC PDU 1 is transmitted repeatedly in the subframe 1 and the MAC PDU 2 is transmitted repeatedly in the subframe 2, until the two MAC PDUs are transmitted for four times. The receiving UE transmits, according to the transmission pattern information, data received in the subframe 1 in the SFN x to an HARQ process 1 for processing, and transmits data received in the subframe 2 in the SFN x to an HARQ process 2 for processing. Data received by the receiving UE in the subframe 1 in the SFN x + 1 is still transmitted to the HARQ process 1 for processing, and data in the subframe 2 is transmitted to the HARQ process 2 for processing. Data received multiple times is demodulated into soft bits at the physical layer, and the soft bits are combined. If a CRC check after the combination is correct, the soft bit buffer in the HARQ process is cleared.
receive, according to the scheduling signaling received by the receiving module 31 and according to a transmission pattern indicated by the transmission pattern information, in a frequency domain position indicated by the frequency domain resource information, in a transmission subframe indicated by the quantity of cycles that can be occupied, the new user data transmitted by the transmitting UE.
In an embodiment, the scheduling signaling further includes an indication that a data packet is new data, where the indication that the data packet is new data is used to indicate that the user data to be transmitted by the transmitting UE is new data; and
the processing module 32 is further configured to:
create, according to the service type, a radio link control RLC entity corresponding to the service type; and
configure parameters of the RLC entity according to a configuration table that is in configuration tables prestored in the receiving UE and corresponds to the service type.
In an embodiment, the scheduling signaling further includes a service type of the user data to be transmitted by the transmitting UE; and
the processing module 32 is further configured to:
Specifically, an RLC layer of the receiving UE creates the RLC entity according to a service type field in the received scheduling information, and configures the parameters of the RLC entity according to the service type in the configuration table. The configuration table is stored by the UE in a hardware device of the UE, for example, in a SIM card, or in other devices such as a communications chip, or may be stored in a memory or a random access memory (Random Access Memory, RAM for short) or a flash memory (flash). The RLC entity configuration parameters include a reordering timer time length (reordering time length) and a packet sequence number reordering window size (reordering window size).
In the receiving user equipment provided by this embodiment, a receiving module 31 receives scheduling signaling transmitted by transmitting UE, where the scheduling signaling includes frequency domain resource information, a quantity of cycles that can be occupied, or transmission pattern information; and a processing module 32 receives, according to the scheduling signaling, user data transmitted by the transmitting UE. Therefore, if there is no feedback from the receiving UE in a D2D communication process, the transmitting UE may repeatedly transmit the user data, and the receiving UE may repeatedly receive the user data and perform combination processing on the received repeated data, thereby improving reliability of data transmission.
FIG. 7
FIG. 7
is a schematic structural diagram of Embodiment 2 of receiving user equipment according to the present invention. As shown in , the transmitting user equipment in this embodiment includes a transmitter 41, a receiver 42, a memory 43, and a processor 44 that is connected to the transmitter 41, the receiver 42, and the memory 43. Certainly, the user equipment may further include a universal component such as an antenna, a baseband processing unit, an intermediate radio frequency processing unit, or an input and output apparatus, which is not limited any longer in the embodiment of the present invention.
The receiver 42 is configured to receive scheduling signaling transmitted by transmitting UE, where the scheduling signaling includes at least one of frequency domain resource information, a quantity of cycles that can be occupied, or transmission pattern information; and the processor 44 is configured to receive, according to the scheduling signaling received by the receiver 42, user data transmitted by the transmitting UE.
repeatedly receive, according to the scheduling signaling received by the receiver 42, according to a transmission pattern indicated by the transmission pattern information, and according to the quantity of times of repeated transmission of the data packet, in a frequency domain position indicated by the frequency domain resource information, in a transmission subframe indicated by the quantity of cycles that can be occupied, the user data repeatedly transmitted by the transmitting UE.
In an embodiment, the scheduling signaling further includes a quantity of times of repeated transmission of a data packet; and
the processor 44 is specifically configured to:
transmit, according to the transmission pattern information, first user data in a first subframe in a first frame to a second automatic repeat request HARQ process corresponding to the first subframe, and transmit, according to the transmission pattern information, second user data in a second subframe in a second frame to a third HARQ process corresponding to the second subframe.
In an embodiment, the processor 44 is further configured to:
receive, according to the scheduling signaling received by the receiver 42 and according to a transmission pattern indicated by the transmission pattern information, in a frequency domain position indicated by the frequency domain resource information, in a transmission subframe indicated by the quantity of cycles that can be occupied, the new user data transmitted by the transmitting UE.
In an embodiment, the scheduling signaling further includes an indication that a data packet is new data, where the indication that the data packet is new data is used to indicate that the user data to be transmitted by the transmitting UE is new data; and
the processor 44 is further configured to:
create, according to the service type, a radio link control RLC entity corresponding to the service type; and
configure parameters of the RLC entity according to a configuration table that is in configuration tables prestored in the receiving UE and corresponds to the service type.
In an embodiment, the scheduling signaling further includes a service type of the user data to be transmitted by the transmitting UE; and
the processor 44 is further configured to:
FIG. 6
The receiving UE in this embodiment is an entity embodiment corresponding to the embodiment shown in , and their implementation principles and technical effects are similar, and are not further described herein.
FIG. 8
FIG. 8
S101. Transmitting UE transmits scheduling signaling to receiving UE, where the scheduling signaling includes at least one of frequency domain resource information, a quantity of cycles that can be occupied, or transmission pattern information.
is a flowchart of Embodiment 1 of a method for data transmission in D2D communication according to the present invention. As shown in , the method for data transmission in D2D communication in this embodiment includes:
Specifically, the frequency domain resource information in the scheduling information in this embodiment may include a frequency domain resource index or a maximum frequency domain resource range. If only one user transmits data at a same transmission time, the frequency domain resource information may be a maximum frequency domain resource range. If multiple users transmit data at a same transmission time, the frequency domain resource information is a frequency domain resource index, and the quantity of cycles that can be occupied is used to indicate a quantity of cycles that can be occupied by user data transmitted by the transmitting UE.
FIG. 2
For a transmission pattern in the scheduling signaling in this embodiment, refer to the schematic diagram of the transmission pattern shown in and related descriptions.
Specifically, the scheduling signaling in this embodiment may include at least one of the frequency domain resource information, the quantity of cycles that can be occupied, and the transmission pattern information. If only one or two of the information are included, the other two or one of the information is fixed.
For example, in a scenario in which the scheduling signaling in this embodiment includes only the frequency domain resource information, the transmission pattern information and the quantity of cycles that can be occupied are fixed. In a scenario in which the scheduling signaling in this embodiment includes only the quantity of cycles that can be occupied, the frequency domain resource information and the transmission pattern information are fixed. It may be specified that a fixed correspondence exists between a frequency domain position occupied by the scheduling signaling and a frequency domain position occupied by the user data. For example, if the scheduling signaling is transmitted in a third symbol of every two PRBs, data information is transmitted in any symbol except the third symbol and a pilot symbol in the two PRBs. In a scenario in which the scheduling signaling in this embodiment includes only the transmission pattern information, the frequency domain resource information and the quantity of cycles that can be occupied are fixed.
S102. The transmitting UE transmits user data to the receiving UE according to the scheduling signaling, so that the receiving UE receives the user data according to the scheduling signaling.
Specifically, the transmitting UE transmits the to-be-transmitted user data according to the frequency domain resource information, the quantity of cycles that can be occupied, and the transmission pattern information in the scheduling signaling, in a frequency domain resource position indicated by the frequency domain resource occupation information, in a transmission time subframe indicated by the quantity of cycles that can be occupied; and the receiving UE receives, according to the transmission pattern indicated by the transmission pattern information, in the frequency domain position indicated by the frequency domain resource information, in the transmission subframe indicated by the quantity of cycles that can be occupied, the user data transmitted by the transmitting UE.
In the method for data transmission in D2D communication according to this embodiment, repeated transmission of user data is determined by transmitting UE, and is not determined according to whether there is any feedback from receiving UE. Therefore, if there is no feedback from the receiving UE in a D2D communication process, the transmitting UE may repeatedly transmit the user data, and the receiving UE may repeatedly receive the user data and perform combination processing on the received repeated data, thereby improving reliability of data transmission.
In the method for data transmission in D2D communication according to this embodiment, transmitting UE transmits scheduling signaling to receiving UE, where the scheduling signaling includes frequency domain resource information, a quantity of cycles that can be occupied, or transmission pattern information; and the transmitting UE transmits user data to the receiving UE according to the scheduling signaling, so that the receiving UE receives the user data according to the scheduling signaling. Therefore, if there is no feedback from the receiving UE in a D2D communication process, the transmitting UE may repeatedly transmit the user data, and the receiving UE may repeatedly receive the user data and perform combination processing on the received repeated data, thereby improving reliability of data transmission.
In an embodiment, the scheduling signaling further includes a quantity of times of repeated transmission of a data packet; and
repeatedly transmitting, by the transmitting UE, the user data to the receiving UE according to the scheduling signaling, according to a transmission pattern indicated by the transmission pattern information, and according to the quantity of times of repeated transmission of the data packet, in a frequency domain position indicated by the frequency domain resource information, in a transmission subframe indicated by the quantity of cycles that can be occupied.
Step S102 may include:
obtaining, by an HARQ process of the transmitting UE, a first PDU in a MAC PDU buffer, and recording a quantity of times of transmission as 0; and
if the HARQ process of the transmitting UE determines, according to an identifier of the HARQ process and the transmission pattern, that a transmission subframe of the first PDU arrives, transmitting the first PDU to the receiving UE by using the transmission subframe of the first PDU, and adding 1 to the quantity of times of transmission, until the quantity of times of transmission reaches the quantity of times of repeated transmission of the data packet.
In an embodiment, the repeatedly transmitting, by the transmitting UE, the user data to the receiving UE according to the scheduling signaling, according to a transmission pattern indicated by the transmission pattern information, and according to the quantity of times of repeated transmission of the data packet, in a frequency domain position indicated by the frequency domain resource information, in a transmission subframe indicated by the quantity of cycles that can be occupied, includes:
FIG. 3
For an RLC module and a MAC module included in the UE in this embodiment, a PDU buffer and the HARQ process included in the MAC module, and a processing procedure of the transmitting UE, refer to the schematic diagram of the UE shown in and related descriptions.
FIG. 4
For a correspondence between a transmission subframe number and an HARQ process identifier in this embodiment, refer to the schematic diagram of a correspondence between a transmission subframe number and an HARQ process identifier shown in and related descriptions.
Further, if a resource corresponding to a first HARQ process is allocated to another transmitting UE for use, the transmitting UE stops using the first HARQ process after the quantity of times of transmission reaches the quantity of times of repeated transmission of the data packet.
For example, processing after the transmission pattern of the transmitting UE is changed is described in this embodiment. When UE B in a D2D group has service data of a higher priority for transmission, a transmission resource of UE A is preempted by UE B, and transmission resources of UE A are reduced. For example, in each frame, two subframes that may transmit data of UE A are reduced to only one subframe that may transmit data of UE A. Therefore, a case in which data in an HARQ process buffer cannot be transmitted again but a quantity of times of repeated transmission is not completed yet may occur, and this is because the HARQ process is associated with a transmission subframe number. To ensure reliable data transmission, UE A may not use the process any longer after continuing to repeatedly transmit the data in the HARQ process buffer for a remaining quantity of times. After obtaining information indicating that the resource may be used, UE B starts to use the resource after waiting for a period equal to a quantity of repetitions multiplied by a repetition interval.
In the method for data transmission in D2D communication according to this embodiment, transmitting UE transmits scheduling signaling to receiving UE, where the scheduling signaling includes frequency domain resource information, a quantity of cycles that can be occupied, transmission pattern information, and a quantity of times of repeated transmission of a data packet; and the transmitting UE repeatedly transmits user data to the receiving UE according to the scheduling signaling, according to a transmission pattern indicated by the transmission pattern information, and according to the quantity of times of repeated transmission of the data packet, in a frequency domain position indicated by the frequency domain resource information, in a transmission subframe indicated by the quantity of cycles that can be occupied. Therefore, if there is no feedback from the receiving UE in a D2D communication process, the transmitting UE may repeatedly transmit the user data, and the receiving UE may repeatedly receive the user data and perform combination processing on the received repeated data, thereby improving reliability of data transmission.
transmitting, by a MAC PDU buffer of the transmitting UE, a second PDU to an HARQ process of the transmitting UE, and recording a quantity of times of transmission as 1, so that when the HARQ process determines that a transmission subframe of the first PDU arrives, the HARQ process transmits the second PDU to the receiving UE by using the transmission subframe of the second PDU; and
when the MAC PDU buffer of the transmitting UE determines, according to the transmission pattern, that a minimum repetition interval expires, transmitting the second PDU to the HARQ process again, until the quantity of times of transmission reaches the quantity of times of repeated transmission of the data packet, where the second PDU includes an identifier of the transmitting HARQ process.
In an embodiment, the repeatedly transmitting, by the transmitting UE, the user data to the receiving UE according to the scheduling signaling, according to a transmission pattern indicated by the transmission pattern information, and according to the quantity of times of repeated transmission of the data packet, in a frequency domain position indicated by the frequency domain resource information, in a transmission subframe indicated by the quantity of cycles that can be occupied, includes:
Specifically, after the HARQ process fetches data, the MAC PDU buffer of the transmitting end may continue to reserve the PDU, and change a counter Current_TX_NB to Current_TX_NB + 1. The HARQ process fetches data from a MAC PDU when performing transmission every time, and the MAC PDU buffer provides appropriate data to the HARQ process according to a transmission status and a repetition status of a PDU. For example, if the transmitting UE obtains transmission capabilities of two consecutive subframes in a frame, a first subframe transmits a MAC PDU 1, and a second subframe must transmit a MAC PDU 2 and cannot continue to transmit the MAC PDU 1, because the scheduling signaling requires that a repeated transmission interval of each packet should not be 0. Therefore, when the repeated transmission interval is satisfied, the MAC PDU buffer provides a repeated data packet to the HARQ process, and a case in which data packets transmitted at the first time and subsequently repeatedly transmitted use different subframe numbers may occur. In this case, the transmitting UE needs to notify, in the data packet, a process number used by the transmitting UE to the receiving end, so that the receiving UE can combine the received repeated data. After receiving a new data packet, the receiving UE demodulates the data packet into soft bits and then transmits the soft bits to an HARQ process buffer corresponding to the data packet, and after a repeated packet of the data packet arrives, also transmits soft bits to a corresponding HARQ process buffer according to a process number carried in the repeated packet and performs combination.
In the method for data transmission in D2D communication according to this embodiment, transmitting UE transmits scheduling signaling to receiving UE, where the scheduling signaling includes frequency domain resource information, a quantity of cycles that can be occupied, transmission pattern information, and a quantity of times of repeated transmission of a data packet; and the transmitting UE repeatedly transmits user data to the receiving UE according to the scheduling signaling, according to a transmission pattern indicated by the transmission pattern information, and according to the quantity of times of repeated transmission of the data packet, in a frequency domain position indicated by the frequency domain resource information, in a transmission subframe indicated by the quantity of cycles that can be occupied. Therefore, if there is no feedback from the receiving UE in a D2D communication process, the transmitting UE may repeatedly transmit the user data, and the receiving UE may repeatedly receive the user data and perform combination processing on the received repeated data, thereby improving reliability of data transmission.
In an embodiment, the scheduling signaling further includes an indication that a data packet is new data, where the indication that the data packet is new data is used to indicate that the user data to be transmitted by the transmitting UE is new data.
Specifically, if the user data to be transmitted by the transmitting UE is new data, the scheduling signaling further includes the indication that the data packet is new data; if the user data to be transmitted by the transmitting UE is data that is transmitted repeatedly, the scheduling signaling does not include the indication that the data packet is new data.
In an embodiment, the scheduling signaling further includes identifier information of the transmitting UE, where the identifier information is used to indicate a priority of using a frequency domain resource by the transmitting UE.
Specifically, the identifier information of the UE may be a global identifier in a large area, or may be an intra-group identifier allocated by a group owner. The identifier information of the UE has a meaning indicating a priority. If another UE also uses a same resource, after the UE detects a collision, UE having smaller UE identifier information may preferentially use the resource.
In an embodiment, the scheduling signaling further includes a service type of the user data to be transmitted by the transmitting UE.
generating, by the transmitting UE, the scheduling signaling; or
receiving, by the transmitting UE, the scheduling signaling transmitted by a base station.
In an embodiment, before the transmitting UE transmits the scheduling signaling to the receiving UE, the method further includes:
Specifically, the scheduling signaling transmitted by the transmitting UE to the receiving UE may be generated by the transmitting UE, or may be received by the transmitting UE from the base station.
In the method for data transmission in D2D communication according to this embodiment, transmitting UE transmits scheduling signaling to receiving UE, where the scheduling signaling includes frequency domain resource information, a quantity of cycles that can be occupied, or transmission pattern information; and the transmitting UE transmits user data to the receiving UE according to the scheduling signaling, so that the receiving UE receives the user data according to the scheduling signaling. Therefore, if there is no feedback from the receiving UE in a D2D communication process, the transmitting UE may repeatedly transmit the user data, and the receiving UE may repeatedly receive the user data and perform combination processing on the received repeated data, thereby improving reliability of data transmission.
FIG. 1
FIG. 5
Embodiment 1 of the foregoing method for data transmission in D2D communication may be performed by the transmitting UE in or .
FIG. 9
FIG. 9
is a flowchart of Embodiment 2 of a method for data transmission in D2D communication according to the present invention. As shown in , the method for data transmission in D2D communication in this embodiment includes:
S501. Receiving UE receives scheduling signaling transmitted by transmitting UE, where the scheduling signaling includes at least one of frequency domain resource information, a quantity of cycles that can be occupied, or transmission pattern information.
S502. The receiving UE receives, according to the scheduling signaling, user data transmitted by the transmitting UE.
In the method for data transmission in D2D communication according to this embodiment, repeated transmission of user data is determined by transmitting UE, and is not determined according to whether there is any feedback from receiving UE. Therefore, if there is no feedback from the receiving UE in a D2D communication process, the transmitting UE may repeatedly transmit the user data, and the receiving UE may repeatedly receive the user data and perform combination processing on the received repeated data, thereby improving reliability of data transmission.
In the method for data transmission in D2D communication according to this embodiment, receiving UE receives scheduling signaling transmitted by transmitting UE, where the scheduling signaling includes frequency domain resource information, a quantity of cycles that can be occupied, or transmission pattern information; and the receiving UE receives, according to the scheduling signaling, user data transmitted by the transmitting UE. Therefore, if there is no feedback from the receiving UE in a D2D communication process, the transmitting UE may repeatedly transmit the user data, and the receiving UE may repeatedly receive the user data and perform combination processing on the received repeated data, thereby improving reliability of data transmission.
In an embodiment, the scheduling signaling further includes a quantity of times of repeated transmission of a data packet; and
repeatedly receiving, by the receiving UE according to the scheduling signaling, according to a transmission pattern indicated by the transmission pattern information, and according to the quantity of times of repeated transmission of the data packet, in a frequency domain position indicated by the frequency domain resource information, in a transmission subframe indicated by the quantity of cycles that can be occupied, the user data repeatedly transmitted by the transmitting UE.
Step S502 may include:
Specifically, the receiving UE receives the data packet according to the frequency domain position and the transmission pattern information that are included in the previously received scheduling signaling. Because the transmitting UE needs to perform repeated transmission for multiple times, the receiving UE needs to demodulate the repeatedly transmitted data at a physical layer and then transmit the data to a soft bit buffer for combination processing, and if a CRC check after combination is correct, deliver the data to an upper layer, or if a CRC check after combination is incorrect, continue to wait for a next repeated data packet, until a quantity of repetitions reaches a quantity of repetitions that is specified by the scheduling signaling. After the data is delivered to the upper layer or a maximum quantity of repetitions is reached or new data is received, the soft bit buffer is cleared.
transmitting, by the receiving UE according to the transmission pattern information, first user data in a first subframe in a first frame to a second automatic repeat request HARQ process corresponding to the first subframe, and transmitting, by the receiving UE according to the transmission pattern information, second user data in a second subframe in a second frame to a third HARQ process corresponding to the second subframe.
In an embodiment, the receiving, by the receiving UE according to the scheduling signaling, according to a transmission pattern indicated by the transmission pattern information, and according to the quantity of times of repeated transmission of the data packet, in a frequency domain position indicated by the frequency domain resource information, in a transmission subframe indicated by the quantity of cycles that can be occupied, the user data repeatedly transmitted by the transmitting UE, includes:
FIG. 3
For example, still using a schematic diagram of UE shown in as an example to describe the receiving UE, the transmitting UE transmits, in a subframe 1 in an SFN x, a MAC PDU 1 corresponding to an RLC 3 service, and transmits, in a subframe 2, a MAC PDU 2 corresponding to an RLC 5 service. Because five repetitions are required, when an SFN x + 1 arrives later, the MAC PDU 1 is transmitted repeatedly in the subframe 1 and the MAC PDU 2 is transmitted repeatedly in the subframe 2, until the two MAC PDUs are transmitted for four times. The receiving UE transmits, according to the transmission pattern information, data received in the subframe 1 in the SFN x to an HARQ process 1 for processing, and transmits data received in the subframe 2 in the SFN x to an HARQ process 2 for processing. Data received by the receiving UE in the subframe 1 in the SFN x + 1 is still transmitted to the HARQ process 1 for processing, and data in the subframe 2 is transmitted to the HARQ process 2 for processing. Data received multiple times is demodulated into soft bits at the physical layer, and the soft bits are combined. If a CRC check after the combination is correct, the soft bit buffer in the HARQ process is cleared.
receiving, by the receiving UE according to the scheduling signaling and according to a transmission pattern indicated by the transmission pattern information, in a frequency domain position indicated by the frequency domain resource information, in a transmission subframe indicated by the quantity of cycles that can be occupied, the new user data transmitted by the transmitting UE.
In an embodiment, the scheduling signaling further includes an indication that a data packet is new data, where the indication that the data packet is new data is used to indicate that the user data to be transmitted by the transmitting UE is new data; and
that the receiving UE receives and processes, according to the scheduling signaling, user data transmitted by the transmitting UE, includes:
creating, by the receiving UE according to the service type, a radio link control RLC entity corresponding to the service type; and
configuring, by the receiving UE, parameters of the RLC entity according to a configuration table that is in configuration tables prestored in the receiving UE and corresponds to the service type.
In an embodiment, the scheduling signaling further includes a service type of the user data to be transmitted by the transmitting UE; and
the method in this embodiment further includes:
Specifically, an RLC layer of the receiving UE creates the RLC entity according to a service type field in the received scheduling information, and configures the parameters of the RLC entity according to the service type in the configuration table. The configuration table is stored by the UE in a hardware device of the UE, for example, in a SIM card, or in other devices such as a communications chip, or may be stored in a memory or a RAM or a flash. The RLC entity configuration parameters include a reordering timer time length and a packet sequence number reordering window size.
In the method for data transmission in D2D communication according to this embodiment, receiving UE receives scheduling signaling transmitted by transmitting UE, where the scheduling signaling includes frequency domain resource information, a quantity of cycles that can be occupied, or transmission pattern information; and the receiving UE receives, according to the scheduling signaling, user data transmitted by the transmitting UE. Therefore, if there is no feedback from the receiving UE in a D2D communication process, the transmitting UE may repeatedly transmit the user data, and the receiving UE may repeatedly receive the user data and perform combination processing on the received repeated data, thereby improving reliability of data transmission.
FIG. 6
FIG. 7
Embodiment 2 of the foregoing method for data transmission in D2D communication may be performed by the transmitting UE in or .
The following describes a method for data transmission in D2D communication according to the present invention by using an interaction process between transmitting UE and receiving UE as an example.
FIG. 10
FIG. 10
S601. Transmitting UE transmits scheduling signaling to receiving UE, where the scheduling signaling includes at least one of frequency domain resource information, a quantity of cycles that can be occupied, or transmission pattern information.
S602. The transmitting UE transmits user data to the receiving UE according to the scheduling signaling.
S603. The receiving UE receives, according to the scheduling signaling, the user data transmitted by the transmitting UE.
is a flowchart of Embodiment 3 of a method for data transmission in D2D communication according to the present invention. As shown in , the method for data transmission in D2D communication in this embodiment includes:
In the method for data transmission in D2D communication according to this embodiment, transmitting UE transmits scheduling signaling to receiving UE, where the scheduling signaling includes frequency domain resource information, a quantity of cycles that can be occupied, or transmission pattern information; the transmitting UE transmits user data to the receiving UE according to the scheduling signaling; and the receiving UE receives, according to the scheduling signaling, the user data transmitted by the transmitting UE. Therefore, if there is no feedback from the receiving UE in a D2D communication process, the transmitting UE may repeatedly transmit the user data, and the receiving UE may repeatedly receive the user data and perform combination processing on the received repeated data, thereby improving reliability of data transmission.
In the several embodiments provided in the present invention, it should be understood that the disclosed apparatus and method may be implemented in other manners. For example, the described apparatus embodiment is merely exemplary. For example, the unit division is merely logical function division and may be other division in actual implementation. For example, a plurality of units or components may be combined or integrated into another system, or some features may be ignored or not performed. In addition, the displayed or discussed mutual couplings or direct couplings or communication connections may be implemented by using some interfaces. The indirect couplings or communication connections between the apparatuses or units may be implemented in electronic, mechanical, or other forms.
The units described as separate parts may or may not be physically separate, and parts displayed as units may or may not be physical units, may be located in one position, or may be distributed on a plurality of network units. Some or all of the units may be selected according to actual needs to achieve the objectives of the solutions of the embodiments.
In addition, functional units in the embodiments of the present invention may be integrated into one processing unit, or each of the units may exist alone physically, or two or more units are integrated into one unit. The integrated unit may be implemented in a form of hardware, or may be implemented in a form of hardware in addition to a software functional unit.
When the foregoing integrated unit is implemented in a form of a software functional unit, the integrated unit may be stored in a computer-readable storage medium. The software functional unit is stored in a storage medium and includes several instructions for instructing a computer device (which may be a personal computer, a server, or a network device) or a processor to perform a part of the steps of the methods described in the embodiments of the present invention. The foregoing storage medium includes: any medium that can store program code, such as a USB flash drive, a removable hard disk, a read-only memory (Read-Only Memory, ROM), a random access memory (Random Access Memory, RAM), a magnetic disk, or an optical disc.
It may be clearly understood by a person skilled in the art that, for the purpose of convenient and brief description, division of the foregoing function modules is taken as an example for illustration. In actual application, the foregoing functions can be allocated to different function modules and implemented according to a requirement, that is, an inner structure of an apparatus is divided into different function modules to implement all or part of the functions described above. For a detailed working process of the foregoing apparatus, reference may be made to a corresponding process in the foregoing method embodiments, and details are not described herein again.
Finally, it should be noted that the foregoing embodiments are merely intended for describing the technical solutions of the present invention, but not for limiting the present invention. Although the present invention is described in detail with reference to the foregoing embodiments, persons of ordinary skill in the art should understand that they may still make modifications to the technical solutions described in the foregoing embodiments or make equivalent replacements to some or all technical features thereof, without departing from the scope of the technical solutions of the embodiments of the present invention. | |
Astronomers have found another possible ‘Exomoon’ beyond our solar system
And then there were two, maybe. Astronomers say they have found a second plausible candidate for a moon beyond our solar system, an ex-moon, orbiting a world nearly 6,000 light-years from Earth. Called Kepler-1708 bi, the moon appears to be a gas-dominated object, slightly smaller than Neptune, orbiting a Jupiter-sized planet around a sun-like star – an unusual planet-moon configuration but not totally unprecedented. The findings appear in natural astronomy. Confirming or disproving the result may not be immediately possible, but given the expected abundance of moons in our galaxy and beyond, it could additionally herald the tentative beginnings of an exciting new era of extrasolar astronomy. , focused not on alien planets but on nature. satellites that orbit them and the possibilities of life therein.
There are over 200 moons in our solar system, and they have an impressive range of variations. Saturn’s moon Titan has a thick atmosphere and freezing hydrocarbon seas on its surface, perhaps an analogue of early Earth. Icy moons such as Jupiter’s Europa are frozen balls that hide subterranean oceans, and they can be prime habitats for life. Still others, like our own moon, are seemingly barren wastelands, but may have water ice in their shadowy craters and labyrinthine networks of subterranean tunnels. One important commonality between these worlds, however, is their mere existence: six of the eight major planets in our solar system have moons. Logic would suggest that the same should be true elsewhere. “Moons are common,” says Jessie Christiansen of the California Institute of Technology. “In our solar system, almost everything has a moon. I’m very confident that moons are all over the galaxy.
The only problem is finding them. We can search for exoplanets in a number of ways, from spying on the dip in light they produce as they move past their star, an event known as a transit, to getting a telltale glimpse of their gravitational tug on their host star. Finding exomoons, which are by nature significantly smaller than the planets they orbit, is much more difficult, however. “They are so small,” says Christiansen. To date, only one truly plausible candidate has been found: Kepler-1625 bi, a supposed Neptune-sized world orbiting a Jupiter-sized exoplanet about 8,000 light-years from Earth that has was reported in October 2018. But even the existence of this more behemothic world has been questioned by later analyses.
The existence of Kepler-1708 bi was first hinted at in 2018, during a review of archival data by David Kipping of Columbia University, one of the discoverers of Kepler-1625 bi, and these partner’work. The team analyzed transit data from NASA’s Kepler Space Telescope of 70 so-called cold giants – gas giants, such as Jupiter and Saturn, that orbit relatively far from their stars, with years consisting of more than 400 Earth days . The team searched for signs of transiting exomoons orbiting these worlds, looking for additional dips in the light of any shadowy lunar companions. Then the researchers spent the next few years killing their darlings, examining one potential exomoon candidate after another, and finding each one best explained by other phenomena, with one exception: Kepler-1708 bi. “He’s a lunar candidate we can’t kill,” Kipping says. “For four years we tried to prove this thing wrong. It has passed every test we can imagine.
The magnitude of the further smaller and relevant dip in light points to the existence of a moon about 2.6 times the size of Earth. The nature of the transit method means that only the radius of worlds can be directly gleaned, not their mass. But the size of this one suggests some sort of gas giant. “It’s probably in the ‘mini Neptune’ category,” Kipping says, referring to a type of world that, although it doesn’t exist in our solar system, is present in abundance around other stars. The planet around which this putative Neptune mini-moon orbits, Jupiter-sized Kepler-1708 b, orbits its star every 737 days at a distance 1.6 times that between Earth and the sun. . Assuming the candidate is truly a moon, it would orbit the planet once every 4.6 Earth days, at a distance of more than 740,000 kilometers, nearly twice the distance of our own orbit. moon around the Earth. The fact that only this single candidate emerged from the analysis of 70 cold giants could suggest that large gas moons are “not super common” in the cosmos, Christiansen says.
The apparently large size of this exomoon, compared to its host planet, is “surprising”, says Kipping, but not entirely unexpected: Kepler-1625 b, the planet on which the previous exomoon candidate Kepler-1625 bi is allegedly in orbit, appears to have a similar configuration, although slightly larger. If these two moons really exist, it could tell us something very interesting about possible planet-moon configurations in the galaxy, namely that giant worlds could host equally giant moons. This in itself raises questions about the genesis of such worlds. It’s unlikely that such a large moon could form directly orbiting a planet, with the planet more likely to sweep away any potential satellite birth material, suggesting that another origin story is more likely. likely.
“One scenario is that this moon was captured by the planet as the planetary system was forming,” says Christiansen. “Early planetary systems are quite violent and chaotic places. We see examples of capture in our own solar system: for example, Triton, one of Neptune’s moons. We believe this was captured. So we know it can happen, we just hadn’t scaled it up to the idea that a Jupiter-sized planet could capture a Neptune-sized moon.
However, not everyone is convinced of the supposed existence of this moon. René Heller of the Max Planck Institute for Solar System Research in Göttingen, Germany, says he’s not sure if the transit signal the team saw was the result of a moon. “That doesn’t convince me,” he said. Instead, Heller adds, the dip in light could simply be the result of natural variations on the star, such as the sunspots we see on our own sun, crossing its surface along with the planetary transit. Kipping and his team, for their part, say they ruled out such a possibility because the supposed plunge caused by the moon began before the planet began to pass in front of the star.
Laura Kreidberg of the Max Planck Institute for Astronomy in Heidelberg, Germany, says she “wouldn’t call it a slam dunk just yet”, but the result is “absolutely worth following” to try and see another transit from the alleged moon. However, we will not be able to do this immediately. Given the planet’s long orbit, it and its eventual moon won’t transit again until 2023, Kipping says, which means we’ll have to wait until then to try to spy on the exomoon again. If the exomoon is really there, the recently deployed James Webb Space Telescope (JWST) would be able to almost instantly confirm or disprove its existence. “It would be a breeze for Webb,” Kipping says. “It could find moons smaller than Europa around Jupiter. It’s a ridiculously powerful telescope.
That in itself raises an exciting possibility: JWST could be used to perform some kind of survey to search for exomoons. In the same way that its predecessor, the Hubble Space Telescope, made huge strides in exoplanet science, JWST may turn out to be defined by its contribution to exomoons. “My team is currently planning what an exomoon investigation would look like strategically for Webb,” Kipping says. “It will be the first time in human history that this will be possible. I’m really excited for the future.
The reasons for doing so are many. Once we start finding exomoons in abundance, we will begin to fully understand their variability and importance. The tides of our own moon, for example, may have played a role in Earth’s habitability, leading to the evolution of life in tidal pools. The study of exomoons can also tell us more about the process of planet formation. “If we want to have a comprehensive understanding of how planet formation works, we need to understand moons,” Kreidberg says. And there’s another, more simplistic reason to study them: “moons are cool.”
Exomoons themselves can also be prime targets in the hunt for life. Given that they can apparently range in size from small to Earth-sized and beyond, it is reasonable to assume that some rocky exomoons can orbit gas giant planets in the habitable zone of their stars, where l liquid water can exist. “This is one of those cases where science fiction might precede science fact,” Christiansen says. “You have the example of the film Avatar of a habitable moon around a gas giant. In star wars, you have habitable moons around the gas giants. You can technically create a rock around a gas giant that has the average radiation from the sun such that it could have liquid water on the surface.
There are, however, complications. A moon around a giant planet would experience considerable gravitational pull and pull from that larger world, which in extreme circumstances, such as Jupiter’s moon Io, can lead to intense volcanic activity. Radiation from gas giants such as Jupiter can also be deadly. And such systems can have special characteristics. “If you’re well aligned, you would have your day and night from your rotation, but an extra day-night cycle to go behind the planet,” Christiansen explains. “There are almost certainly rocks at the right temperature around the gas giants. Whether they are habitable or not is an open question and something that many people are excited about. | https://floatingplanet.net/astronomers-have-found-another-possible-exomoon-beyond-our-solar-system/ |
Coming from landlocked Tennessee, Cash knows that plastic pollution isn’t just an ocean problem but a world problem, and a river problem. In his words: “Most ocean plastic actually starts on land and is blown or swept into rivers where it makes its way to the ocean. 80% starts on land so if we only focus on our oceans there will be little improvement but people in landlocked states, like me, don’t understand their impact on the ocean.”
Cash has done several river clean-ups along the Tennessee River, finding the majority of trash to be single-use plastic, along with fishing lines left along the banks and not disposed of, causing potential harm and death to our amazing wildlife.
Cash’s campaign aims to reduce the amount of single-use plastic and fishing lines in waste streams. His goal is to stop plastic pollution from reaching our oceans by addressing it at its source: “If we can increase the recycling efforts inland and the coastal efforts continue we will eventually have cleaner water and a healthier planet.”
Through his research, Cash learned that the Tennessee River is the most microplastic-polluted body of water in the world. This is more than likely due to landfill waste and lack of recycling in our southern states. Cash plans to place recycle bins, fishing line receptacles, and educational material primarily at local fishing holes and recycle bins at golf courses. Through a grant provided by the Ocean Heroes Network, Cash has been able to purchase recycling bins and other educational material to provide along the Tennessee River.
Recently, Cash was featured on the Kelly Clarkson Show with fellow Ocean Hero Chloe Mei. Watch their interview here: | https://oceanheroeshq.com/cash-revitalizes-the-rivers/ |
Chinese Artist Hides Optical Illusions in Plain Sight
A 33-year-old artist from Chenzou, China, has been getting a lot of attention for turning trees, utility poles, and road signs into optical illusions that blend into their backgrounds.
Huang Yao is a talented 3D painter who showcases his skills by turning local infrastructure and plant life into original artworks. The young Chinese specializes in creating perfect camouflage for his creations, which makes them blend into the background perfectly. But that would mean that most people either walk right by them without even noticing his stunning work, or run straight into them and injure themselves. Neither case is ideal, so Huang usually adds certain elements to make his optical illusions stand out. | https://designyoutrust.com/2022/11/chinese-artist-hides-optical-illusions-in-plain-sight/ |
DU B.Ed Entrance Exam 2019 Application Form, Dates, Eligibility, Syllabus, Pattern
Delhi University (DU) is a premier university in the country of highest academic standards. It is established in 1922 as a unitary, teaching & residential University by the act of Central Legislative Assembly. Delhi University 90 college under 16 faculties with 87 departments & 13 centres. DU will release its notification regarding Bachelors in Education (B.Ed) Entrance Exam; this exam is conducted by the DU itself for the candidates to take admission in 2 years Bachelor in Education course.
|DU B.Ed 2019 Application Form||DU B.ED Eligibility||DU B.ED Admission Process||DU B.ED Exam Pattern|
- DU B.Ed Entrance Exam consists of MCQ type, which is of 100 marks divided into four parts.
- Paper-I consists of questions from GK & Teaching Aptitude, Paper-II consist of Reasoning, Paper-III consist of questions from Subject knowledge up to class X & paper-4 consist of Language Proficiency in Hindi & English.
- DU authority will release separate merit list for each category (GEN/ SC/ ST/ OBC).
- After the declaration of result successfully qualifying candidates will be eligible for counselling process which will be conducted by Delhi University at Central Institute of Education.
DU B.Ed Exam Dates 2019
|Event||Date|
|Commencement of online application||First week of May 2019|
|Last date for submission of online application||Last week of May 2019|
|DU B.Ed Admit Card||First week of June 2019|
|DU B.Ed Exam Date 2019||June 18, 2019|
|Declaration of Result||July 2, 2019|
|DU B.Ed Counselling Process||Last week of July 2019|
DU B.Ed Eligibility Criteria 2019
Delhi University sets the eligibility criteria for B.Ed program. The eligibility criteria vary according to the category. Check Eligibility Criteria for DU B.Ed given below.
For B.Ed program – Candidates must have a Graduation or Master degree in Science, Humanities, Commerce with at least 50% of marks. Candidates with B.Tech/ B.E degree must have obtained 55% of marks with specialization in Science and Mathematics are eligible for admission to the program.
Eligibility for Choosing Teaching Subject – Candidates have to choose one subject within a subject category which they must have studied in the qualifying degree for at least 200 marks and obtained at least 50% marks in this subject.
Candidates belonging to SC/ ST/ PWD category must be passed only in their qualifying examination. There is a relaxation of 5% marks in aggregate for OBC category.
DU B.Ed Application Form 2019
DU B.Ed Application Form will be available from June 2019 on the official website i.e. www.cie.du.ac.in. Candidates must ensure the eligibility before filling up the online application form. Candidates willing to apply for DU B.Ed can check the step-wise procedure as mentioned below.
- Visit the official website of Delhi University PG admission i.e. www.admission.du.ac.in
- Go to the link of CIE i.e. cie.du.ac.in. Download B.Ed prospectus and read all the instructions carefully.
- Click on the Apply Online link and fill the required details in the application form such as personal, educational details.
- Make the payment through online mode (Credit/ Debit card or net banking) or in offline mode through Challan at any SBI branch.
- Verify all the entered details in the application form and click on the submit button.
- No changes in the form are allowed once the payment has been made. After the payment is made, take a printout of the form and bring it on the day of counselling at the time of admission.
DU B.Ed Admit Card 2019
DU B.Ed Admit Card will be issued to only those candidates who have successfully completed the application process. Candidates can download the DU B.ed Admit Card by providing their Application ID and Password on the official website. No candidate is allowed to appear for entrance test without admit card. An admit card is an important document as it contains Roll Number, Address of the Exam Center, Exam Timing and Reporting Time etc. Check the following steps to know that how to download admit card.
- Go to the official website of DU admissions. i.e. www.cie.du.ac.in
- Click on the link of admit card and enter the login credentials.
- Click on the submit button and the admit card page will appear on the screen.
- Take a printout of the page for its future reference.
DU B.Ed Exam Pattern & Syllabus
The admissions in B.Ed will be done through Entrance Test conducted by the university. The paper consists of 100 multiple choice questions from Reasoning, General Knowledge, Language Proficiency and Fundamentals. Each question carries one mark. DU has a negative marking provision and 0.25 marks will be deducted for every wrong answer. The total duration of the examination is two hours. The medium of the paper is bilingual i.e. English and Hindi. Check the following table to know DU B.Ed Exam Pattern 2019.
|Code||Section||Marks|
|A||General Awareness and Teaching Aptitude||30|
|B||Reasoning||20|
|C||Fundamentals (Subject Knowledge upto Class 10th)||30|
|D||Language Proficiency||20|
Here, we take a comprehensive look at all the sections, check the type of questions which are asked in the examination in each section.
General Knowledge and Teaching Aptitude - This section contains questions that would test the candidate’s general knowledge and awareness of social, political, environmental, and economic issues. The section also contains questions to examine the perspectives and analysis of and responses to teaching and learning situations.
Reasoning – This section will assess the mathematical, logical, and verbal reasoning abilities. It will also assess candidates’ abilities to analyse and interpret data and find solutions to problematic situations.
Subject Knowledge up to class 10th – This section will contain questions based on understanding and application of concepts in Science, Social Science and Mathematics up to secondary level.
Language Proficiency – This section will assess reading comprehension in both English and Hindi.
DU B.Ed 2019 Results
- Candidates will be shortlisted for the counselling process on the basis of merit list released by the examination authority.
- The merit list is prepared on the basis of marks obtained in the entrance test. DU B.Ed Result will be declared within a week after the exam date.
- DU B.Ed merit list for qualified candidates will be displayed on the official list and candidates can check the rank they have secured.
- The qualifying marks for general category is 20 out of 100 marks while it is 18 marks for reserved categories.
- The separate merit list will be displayed for each category and subject category.
- If two or more candidates having equal marks, then candidate with older in age will be preferred for the counselling.
DU B.Ed Counselling Process 2019
Candidates will be called for counselling process at Central Institute of Education on the basis of rank secured in the merit list. DU B.Ed counselling will start after the declaration of result in July 2019. The name of selected candidates in the merit list does not indicate final selection for admission. The general merit list will comprise of candidates of all categories in the order of merit. No one will be excluded from the same. In other words, it will also include SC/ ST/ OBC candidates if they come in the general merit. A list of candidates selected will be prepared strictly in order of merit, based on their performance in the Entrance Test and their preference of institutions during Counseling. The shortlisted candidates for counselling have to appear at the stipulated date and time along with the following documents as given below.
- Photo Identification Proof
- Copy of the application form
- DU B.Ed 2019 Admit Card
- Two Recent Colored Photograph
- Mark Sheet and Certificates of Class 10th and 12th
- Mark Sheet of the qualifying Examination
- Provisional Letter and Character Certificate from the institution last attended
- In case of candidates in service, they have to produce No Objection Certificate from the employer and a letter of sanction of study leave for a period of two years.
If a candidate fails to submit any of the above documents at the time of admission, then their candidature will be cancelled.
Important Instructions Regarding DU B.Ed Admission
Candidates screened through the counselling will have to complete the admission related formalities within the stipulated period of time in the respective institutions allotted during counseling.
If they fail to do so, the offer will be withdrawn and the seats will be allotted to candidates next in the merit list during the subsequent counseling. Their selection will stand automatically cancelled without any further notice. Once allocated, no request for change of institution shall be entertained.
Candidates whose results are awaited must also report for counseling at the stipulated time. Candidates selected for admission to the B.Ed. Programme, are required to complete the admission related formalities within the stipulated period of time including payment of the requisite fee at the time of admission.
Candidates who do not have their results of the qualifying degree will not be allowed for provisional admission. However, they will be considered for admission in the subsequent admission lists, provided:
- Candidates report for counseling on the dates mentioned when their names appear in the merit list.
- Seats are available in the particular subject category when the candidate reports with the result.
DU B.Ed Reservation Criteria
The seats reserved for SC/ ST category will be filled by those candidates only. In the case of non-availability of the eligible candidates the reserved seats may be interchanged between the SC and ST. If still any seat remains unfilled, the same will be left vacant. The seats reserved for the OBC are filled with the OBC candidates only. Only if OBC candidates possessing the minimum eligibility marks are not available in the OBC category then the vacant OBC seats will be converted into General Category seats in accordance with the admission schedule notified by the University.
Wards or widows of the eligible armed forces personnel including Para Military forces having reservation of 5% of the seats in each course. Candidates can go through the following table to check the reservation of seats.
|Category||Reservation|
|OBC||27%|
|SC||15%|
|ST||7.5%|
|PWD||3%|
DU B.Ed Seat Intake
There are total 100 seats available in B.Ed program in various participating colleges. The department has changed the number of seats in CIE, it is 32 for Social sciences and 12 for Other subjects. Candidates can refer to the below table to check the total number seats.
|Subject Category||Number of Seats|
|CIE (Central Institute of Education||Lady Irwin College||Maharishi Valmiki College of Education||SPM College|
|Science (Physics, Chemistry, Biology, Mathematics, Home Science)||32||100||32||16|
|Languages (English, Hindi, Sanskrit)||24||-||24||12|
|Social Sciences (History, Political Science, Geography, Economics)||32||-||32||16|
|Other Subjects (Commerce, Sociology, Psychology)||12||-||8||6|
|Other Languages (Punjabi, Urdu)||-||-||4||-|
|Total Seats||100||100||100||100|
Here are some colleges which offer B.Ed program via DU B.Ed entrance exam. | https://collegedunia.com/exams/du-bed-entrance-exam |
- Do you experience challenges related to bullying, prejudice and discrimination in your school?
- Would you like to see your students cooperating more and competing less?
- Do you feel that you are not always reaching out to your students in classroom interaction?
If these questions sound familiar to you, this self-reflection tool might be the right companion for you.
If you are interested in what democracy in school is actually about and what this has to do with yourself and with your professional teacher ethos, we invite you to follow us on a journey towards the development of and reflection on your own competences for democratic culture.
The qualities we need to contribute to a democratic school culture are not something you learn once, but something which constantly needs to be developed, maintained and adjusted in new situations and contexts. Each encounter with students, colleagues or parents brings new opportunities for interaction, cooperation and learning – as well as new challenges and possible conflict. It takes a lot from a teacher to realise the potentials for learning, cooperation and personal growth and to solve the challenges in constructive and respectful ways. Often the way ahead is through trial and error, and failure is therefore a part of that process, a part of becoming and being a “good teacher” (Biesta 2015; Larivee 2000). And it is a part of what we call a democratic teacher ethos.
Democratic knowledge, democratic attitudes, democratic skills and democratic values as outlined in the model of the Council of Europe’s Reference Framework of Competences for Democratic Culture (RFCDC) play an essential role in the development of a professional teacher ethos, which builds on the values of democracy and human rights. Teaching democracy and human rights in order to be credible and sustainable needs a teaching environment based on democratic principles, including a democratic attitude of teachers, participation of the learners in the learning process, and not least the ability to critically reflect on and adapt your own teaching activities.
So, this tool is for you if you would like to develop on a continual basis democratic professional ethos and competences, under conditions that are not always favourable. It will help you structure your work according to democratic competences, using the reflective circle of planning – doing – reflecting – adapting. While this slows you down during the reflection phase, it ultimately increases your speed for improving your teaching activities and your pedagogical practice in general.
CDC are not only relevant for the educational sector, but also democratic culture in general. The 20 competence elements in the CDC model and the related descriptors can help us to reflect on our how we do things, how we interact with people, how we cooperate and how we solve conflict. Developing CDC is a personal development.
However, CDC is most relevant in the context of education. Teachers and other educators have a massive impact on learners as significant others, role models and facilitators of learning processes and are far more than transmitters of knowledge. Educators can support learners in becoming independent thinkers, good co-operators, and self-confident participants in dialogue, discussion and decision-making. They can support learners in becoming active citizens.
As a “democratic teacher” you are required to be much more than just “good” in your subject. It requires a lot of what CDC is about: the ability to listen to learners, colleagues and parents; openness to the cultural affiliations and practices they bring into the educational process; empathy and a sense of responsibility for the well-being and empowerment of all learners, to name but a few.
A teacher’s way of teaching and interacting has an important impact on the classroom climate and the individual’s learner’s well-being and achievements. These aspects of the professional practice can be learned and systematically developed.
Pedagogical professionalism is a matter of constant development and, thus, depends on the ability and willingness for self-observation and self-reflection (Schoen 1983, Bailey 2001). This is even more evident when it comes to the development of democratic and inclusive learning environments. Carr and Kemnis (Carr, Kemnis 1986, 2005) underline, that democratic change can only be reached through continuous and collaborative reflection on practice. In this context, the teacher’s professional development is at the same time a personal development: a democratic teacher wants to examine their own democratic attitudes; they want to question their own methods and learn from their interactions with the learners. The mental step back and the changing of perspectives enables us to analyse and change our own strengths and weaknesses and to further develop our professional democratic competences. From this perspective, self-reflection can be understood as the intensive examination of one's own learning and teaching processes with regard to CDC. This directly links to the Council of Europe’s EDC/HRE Charter , which states, that “teaching and learning practices and activities should follow and promote democratic and human rights values and principles” (section 5.e) (see also RFCDC, vol. 1, p. 17).
Purpose of this tool
The purpose of this tool is to accompany teachers and multipliers in this process and in their work with the Council of Europe’s Reference Framework of Competences for Democratic Culture (RFCDC). It can be used as a starter to get acquainted with the RFCDC but can also be seen as a very general companion to self-reflection on teaching and democratic competences. This tool can guide you and structure your journey of exploring and developing your role and practice as a teacher, while allowing you to decide how much time and effort you wish to spend on it.
The teacher reflection tool addresses all practitioners at all levels (in-service and pre-service; acquainted or not acquainted with RFCDC) and can be used on an individual basis, as well as a basis for group or peer reflection.
Education for democracy and inclusive education need both reflective practitioners and a reflective school culture. This tool aims at giving teachers the impulses for self-reflection, which in turn form the basis for a reflective school culture.
A school culture based on self-reflection can use many methods and tools, including observation, peer feedback, group reflection in the team of teachers, communities of practice etc. This tool can be combined with all of these methods and can easily be integrated in larger school development processes.
This material is published as one of the tools that support implementation of the Reference Framework of Competences for Democratic Culture (RFCDC) in schools. It also supports the Council of Europe’s efforts to build a European network of democratic schools; by focusing on the teachers' competences and on their professional ethos, it acknowledges the importance of teachers for the whole-school system. In order to enable the best possible synergies between the different Council of Europe initiatives, the tool was aligned with the six major themes of the Council of Europe’s “Free to Speak, Safe to Learn – Democratic Schools for All” project. These themes represent both central preconditions for democratic culture in education as well as challenges which need to be solved in democratic ways. You can select the topics which seem to be closest to your own interest or most relevant in your own context, or you can discover new aspects of democratic education while working through all the modules.
Before beginning the modules in part IV, we recommend you try one or all of the steps in part III for familiarising yourself with observation and self-observation, but these activities can be done at any point.
Structure of the tool
- Making children’s and students’ voices heard
- Addressing controversial issues
- Preventing violence and bullying
- Dealing with propaganda, misinformation and fake news
- Tackling discrimination
- A brief introductory section to each topic shows the relevance of the issue in the school context, links to the field of CDC and opens the floor with some guiding questions for reflection.
- A ready-made scenario that allows for analysis and comparison with your own teaching practices can be used as a warm up and for becoming acquainted with the specific topic.
- In a next step, you will be guided through a reflection process on your own teaching activities and projects.
- In order to get familiar with reflection
- From time to time as a stimulus for reflection
- In a structured way in your daily work
- As a “course” in your teacher training
- For team reflection
- If you prefer to have the concepts clear first, start with reading the RFCDC, then take the quiz and then move to the other sections
- If you prefer to do something, explore something practical and get to conceptual clarifications only when and if needed, then select any thematic module and, when you identify the need, go to the RFCDC in brief and clarify the relevant concepts
- If you prefer to reflect first on yourself and then think about concepts and/or practice, start with the Warming-up section.
Discovering the model of competences for democratic culture
Warming up – familiarising yourself with observation, reflection and self-reflection on CDC
This section makes you more familiar with the exercise of observation and self-observation and how the CDC descriptors can support your personal and professional development. The section will start with exploring everyday situations in which you may use your competences for democratic culture. It continues with reflection on your strengths as a democratic teacher and how to develop them as an ongoing process. In a last step, the section turns to the “hot moments” in a teacher’s life; situations you find challenging and in which you do not feel that you live up to your own standards as a pedagogue and person. With the help of CDC and the descriptors, the section will guide you through a reflection on how to solve such “hot moments” in more appropriate ways.
The modules: reflective modules following the focus themes of the Council of Europe’s project “Free to Speak, Safe to Learn – Democratic Schools for All”.
The modules can be done in any order; each module is a separate, independent unit.
Each module follows the same structure, which allows you to get familiar with the specific topic and come to conclusions how to improve your respective competences.
The tool can be used on an individual or peer-to-peer basis. It also enables collective reflexion processes of the entire staff of a school. It can support and empower you in any condition regardless of your experience or of how far you have come on your journey to create a democratic school.
No matter whether you are already experienced or hear the first time about RFCDC – this tool can become a companion for your professional life.
You can use it
Some possible entry points and ways of using the TRT
You are certainly familiar with the RFCDC:
=> You can start with personal reflections in the Warming-up section or choose directly a thematic module that interests you.
You are somewhat familiar with the RFCDC but not sure about some aspects:
=> You can take the quiz. If you get a perfect score, you can do as indicated above. If not, you may want to read the RFCDC in Brief and then take the quiz again
You are now discovering the RFCDC:
=> depending on your preferred learning and working style you can choose one of the options described below (but you can also build a path through the tool in your own way)
Further reading and links:
Bailey, K. M., Curtis A., & Nunan D. (2001). Pursuing professional development: th e self as source. Toronto: Heinle & Heinle Publishers.
Biesta, G. J. J. (2015). How does a competent teacher become a good teacher? On judgement, wisdom and virtuosity in teaching and teacher education. In R. Heilbronn & L. Foreman-Peck (Eds.), Philosophical perspectives on the future of teacher education (pp. 3–22). Oxford: Wiley Blackwell.
Larrivee, B. (2000) Transforming Teaching Practice: Becoming the critically reflective teacher, Reflective Practice, 1:3, 293-307, DOI: 10.1080/713693162
Schoen, D. (1983): The reflective practitioner: how professionals think in action, Basic Books, New York.
Zembylas, M. (2003). Interrogating “Teacher Identity”: Emotion, Resistance, and Self- Formation. Educational theory, 53(1), 107-127.
Resources:
Council of Europe (2017) Reference Framework Competences for Democratic Culture (Vol. 1.–3.). Available at https://www.coe.int/en/web/reference-framework...
The Coaching and Self-Reflection Tool for Competency in Teaching English Learners
https://portal.ct.gov/-/media/SDE/Publications/...
Making Teacher Reflection Meaningful
https://www.educationworld.com/making-teacher-reflection-meaningful Reflection Tools in Teacher Education Classes: An Analysis of Implementation in Online, Hybrid, and Traditional Environments
www.tojet.net/articles/v14i2/14217.pdf
Ontario College of Teachers: A Self-Reflective Professional Learning Tool.
https://www.oct.ca/-/media/PDF/A%20Self%20Reflective%...
Teacher Self-Assessment Tools (ref RFCDC Vol III/pedagogy)
https://www.tesol.org/docs/default-source/...
You can download the three RFCDC volumes from the relevant website . For the purpose of the self-reflection tool, Volume 1 “Context, concepts and model”, and Volume 3 ”Guidance for implementation” (Curriculum, Pedagogy, Assessment, Teacher education, Whole-school approach, Building resilience to radicalisation leading to violent extremism and terrorism) are especially important. | http://trt.intercultural.ro/info/about-the-tool |
Abstract:The paper describes two economics terms consumer surplus and producer surplus using the definite integrals (the Riemann integral). The consumer surplus is the difference between what consumers are willing to pay and actual price. The producer surplus is the difference between what producers selling at the current price, rather than at the price they would have been are willing to accept. Using the definite integrals describe terms and mathematical formulas of the consumer surplus and the producer surplus and will be applied to the numerical examples. | https://publications.waset.org/abstracts/29101/calculate-consumer-surplus-and-producer-surplus-using-integration |
The Milan Complexity Scale—a new practical grading scale designed to estimate the risk of neurological clinical worsening after performing surgery for tumor removal—is presented.
METHODS
A retrospective study was conducted on all elective consecutive surgical procedures for tumor resection between January 2012 and December 2014 at the Second Division of Neurosurgery at Fondazione IRCCS Istituto Neurologico Carlo Besta of Milan. A prospective database dedicated to reporting complications and all clinical and radiological data was retrospectively reviewed. The Karnofsky Performance Scale (KPS) was used to classify each patient’s health status. Complications were divided into major and minor and recorded based on etiology and required treatment. A logistic regression model was used to identify possible predictors of clinical worsening after surgery in terms of changes between the preoperative and discharge KPS scores. Statistically significant predictors were rated based on their odds ratios in order to build an ad hoc complexity scale. For each patient, a corresponding total score was calculated, and ANOVA was performed to compare the mean total scores between the improved/unchanged and worsened patients. Relative risk (RR) and chi-square statistics were employed to provide the risk of worsening after surgery for each total score.
RESULTS
The case series was composed of 746 patients (53.2% female; mean age 51.3 ± 17.1). The most common tumors were meningiomas (28.6%) and glioblastomas (24.1%). The mortality rate was 0.94%, the major complication rate was 9.1%, and the minor complication rate was 32.6%. Of 746 patients, 523 (70.1%) patients improved or remained unchanged, and 223 (29.9%) patients worsened. The following factors were found to be statistically significant predictors of the change in KPS scores: tumor size larger than 4 cm, cranial nerve manipulation, major brain vessel manipulation, posterior fossa location, and eloquent area involvement (Nagelkerke R2 = 0.286). A grading scale was obtained with scores ranging between 0 and 8. Worsened patients showed mean total scores that were significantly higher than the improved/unchanged scores (3.24 ± 1.55 vs 1.47 ± 1.58; p < 0.001). Finally, a grid was developed to show the risk of worsening after surgery for each total score: scores higher than 3 are suggestive of worse clinical outcome.
CONCLUSIONS
Through the evaluation of the 5 aforementioned parameters—the Big Five—the Milan Complexity Scale enables neurosurgeons to estimate the risk of a negative clinical course after brain tumor surgery and share these data with the patient. Furthermore, the Milan Complexity Scale could be used for research and educational purposes and better health system management. | https://thejns.org/search?authf=Raggi%2C+Alberto&f_0=author&pageSize=10&q_0=Marco+Schiariti&sort=relevance |
What was the impact of the development of agriculture in the evolution of Mesoamerican civilization?
1 Answer | Add Yours
The development of agriculture enabled Mesoamerican peoples to form large, settled societies that developed centralized governments and high levels of social and political stratification. The reason for this, in a broad sense, is that societies that produce surpluses can afford to maintain elites that draw their status from the ability to extract wealth from the rest of society. In Mesoamerica, the main crops were maize, beans, and squash, three symbiotic vegetable plants which were cultivated in fields alongside each other. In the subtropical climate of Central America, they yielded large quantities of food, enough to support the cities that made up the series of civilizations that rose in the area, including the Olmecs, Zapotecs, Aztecs, and Maya, to name a few. Agriculture was instrumental in the development of these dense, complex societies. | http://www.enotes.com/homework-help/what-was-impact-agricultural-revolution-evolution-366817 |
Mailing Address:
43 Foundry Avenue
Waltham, Massachusetts 02453-8313
Telephone:
As Director of Research, Evaluation, and Policy, Jill Weber oversees a team of researchers and evaluators in supporting education leaders and policymakers in gathering and using data to guide decision-making, strengthen programs and systems, and improve outcomes for preK-12 students. To this work, she brings extensive expertise in policy development and analysis, assessment and accountability, educational technology and online learning, and curriculum development.
Weber leads a growing portfolio of research and evaluation work at EDC connected to and in support of national and local priorities. This work allows pre-K–16 educators at the state, district, and school levels to use the best available research and evidence to make decisions leading to improved student achievement and reduced performance gaps among student groups. Weber has extensive management experience in both for- and not-for-profit settings working on complex projects with multiple partners. Her focus spans the range of work from needs analysis to responsiveness to state and district needs, to dissemination of research findings and support for the measurement of impact and effectiveness.
Weber is Director of the Regional Educational Laboratory Northeast and Islands, funded by the Institute of Education Science, U.S. Department of Education, which provides educators and policymakers with access to high-quality scientifically valid education research through applied research and development projects, randomized controlled trial studies, dissemination of research findings, and related technical assistance activities. Weber works with state and local education agency leaders in New England, New York, Puerto Rico and the Virgin Islands. Her work has been funded by the Department of Education and the Institute of Education Sciences.
Before joining EDC, at TERC Weber was Project Director for Massachusetts Empowering Educators with Technology (MEET) and for the federally funded Northeast and Islands Regional Technology in Education Consortium (NEIRTEC). Before TERC, she was a technology coordinator in Salem and Cambridge, Mass., schools.
Weber received a BS in education from the University of Wisconsin–Madison, an EdM from Harvard University, and an MBA from the University of Dayton, in Ohio. | http://ltd.edc.org/people/jill-weber |
85) Um livro sobre as guerras e a tecnologia atras delas...
Review
Conspicuous Proliferation
by Max Boot
Gotham, 624 pp., $35.00
War Made New begins with a crisp introduction, sketching four revolutions in warfare since 1500 around which Max Boot chose to organize his book. It ends in a fog of acronyms for weapons still on the drawing boards, uncertainty about future military revolutions, and "The Danger of Too Much Change—and Too Little." In between Boot found many persuasive things to say about how changes in military technology and management affected the course of European and world history, illustrating each of his military revolutions with detailed accounts of three specific battles or campaigns.
The first of these changes, the "Gunpowder Revolution," actually started in China, but Boot does not discuss that. Instead he confines his attention to Europe, where, he says, gunpowder was first recorded as early as 1267. But it remained of marginal importance until 1494, when a French army marched into Italy with mobile siege guns, easily shattering hitherto impregnable fortifications with a few hours of bombardment, only to withdraw without any lasting gain, while spreading the nasty new disease of syphilis far and wide as it retreated.
Boot illustrates the Gunpowder Revolution by choosing first to describe how the Spanish Armada was defeated by the superior guns and tactics of the English navy (1588) and how Swedish soldiers won two hard-fought victories during the Thirty Years' War in Germany at Breitenfeld and Lützen (1631–1632). His accounts of these battles are admirably clear and concise; but they are also thoroughly familiar and offer no new insights. One may even reproach him for a kind of blindness, since he never mentions the conscious purposes of the persons who planned and fought them, apparently assuming that their religious convictions, hopes, and fears had nothing to do with what happened.
I learned a lot, however, from what he says about the Battle of Assaye in India in 1803, with which he concludes the first part of his book. He uses it to show how the Gunpowder Revolution opened a wide gap between European and Asian efficacy in war. For the Battle of Assaye was where Sir Arthur Wellesley (later Duke of Wellington), in command of the East India Company's British and sepoy troops, established his reputation by defeating a much larger Maratha force. The still youthful Wellesley prevailed by dint of reckless audacity, backed up by the superior tenacity and discipline of his soldiers.
The Battle of Assaye was, Boot tells us, "one of the two bloodiest engagements that the Duke of Wellington ever fought (Waterloo was the other), and the one of which he was proudest later in life." It resulted in a substantial enlargement of British-administered territories in India, and marked the end of military competition between the East India Company and native Indian rulers.
I had supposed that Robert Clive's earlier victory at Plassey in 1757 was the principal step in establishing British military supremacy in India. Boot does not even mention Plassey, but his account of Assaye makes it clear that Clive's easy victory over vastly superior numbers was not really decisive. For Indian rulers, most notably a cluster of Maratha chieftains in western India, reacted to the defeat at Plassey by systematically imitating European weapons and drill, in hope of defeating the white intruders. European weapons were readily available for purchase and so were experienced European gunners and drill masters, including a few Britons. In less than half a century the Marathas were therefore able to create infantry and artillery units just as good as the sepoys in British service. That was why the Battle of Assaye was so bloody and hard fought; the outcome did not depend on large-scale desertion and betrayal, as had happened at Plassey.
Yet the Maratha armies still suffered from critical shortcomings, as Boot explains:
Lacking a single commander like Wellesley whose orders were binding on all, the Maratha chieftains often would act at cross-purposes in battle, to the benefit of their enemies. Moreover, their supply service was virtually nonexistant and most of their soldiers were not paid regularly....
The real problem was that the Marathas were handicapped by a lack of officers and NCOs schooled in the new way of fighting.... To turn over ultimate military power to Westerners or even to Western-educated Indians would have meant giving up their own absolute authority, and this the Maratha chiefs would never do....
In sum, to fight like Europeans you had to become "European."You had to adopt at least some of the dynamism, intellectual curiosity, rationalism, and efficiency that has defined the West since the advent of the Gunpowder Age.
Since Colonel Blimps always outnumbered and usually prevailed over military innovators, this is a dubious description of European armed forces. But the difficulty of equaling them in battle was real and it gave Europeans more than a century of easy successes, imposing a uniquely lopsided, imperial character on the nineteenth and early twentieth centuries. Boot's dating of the tipping point in favor of European military superiority as late as 1803 is both novel and convincing, for China too succumbed to European aggression only after the Opium War between 1839 and 1842.
At the same time, however, so late a date blurs the transition between his first military revolution and the "Industrial Revolution" in military technology that followed. Historians have long agreed that the Industrial Revolution itself started in Great Britain with the mechanization of textile manufacture between 1733 and 1793 and extended to other industries after James Watt invented an efficient steam engine in 1776. But Boot claims that military change lagged:
In the late eighteenth and early nineteenth centuries, logistics and command-and-control systems could not keep pace with the growing size of armies. Supplies still had to be hauled by horses; muskets, cannons, ammunition, and uniforms still had to be hand-made by skilled artisans; orders still had to be relayed by bugles, shouts, and messages carried on horseback; and commanders still had to depend on their spy glasses to figure out what was happening on a smoke-shrouded battlefield....
Napoleon brought the old style of war to its ruthless zenith; he did not invent a new style. At most, by stoking the fires of nationalism, the Napoleonic era blazed a path for a true revolution in warfare when mass production could be combined with mass mobilization.
This combination, Boot claims, only began with the Crimean War between 1854 and 1856. But such an assertion disregards far-reaching improvements in French and British artillery and metallurgy after 1750, when new ways of casting, boring, aiming, and transporting artillery, together with coke-fired furnaces and increasingly systematic administration of personnel and supply services, expanded the military capacities of both countries very rapidly indeed.
Moreover, what Boot refers to as "stoking the fires of nationalism" involved an intensification of warfare that surely deserves to be called revolutionary. For the levée en masse that saved the French Jacobins in 1793 was justified and sustained by a new secular faith proclaiming "the rights of man"—liberty, equality, and fraternity. Accordingly, French armies claimed to be liberators when they invaded Germany and other West European countries. Initially, many Belgians, Dutch, and Germans welcomed them as such, but the French soon outwore their welcome by flaunting a sense of their own superiority. Moreover, their demands for material contributions for the support of the occupying armies turned popular feeling against them and everything they stood for, first in Spain, then in Germany. Spreading national consciousness swiftly provoked a new intensity of mobilization against the French that overthrew Napoleon and his empire in 1814 and 1815. To dismiss such upheavals as merely continuing the same style of war strikes me as completely wrongheaded.
Boot also implausibly postpones his "First Industrial Revolution" in military production by choosing to illustrate its impact only after 1866, describing the Battle of Königgrätz in Bohemia between Prussia and Austria in 1866, the Battle of Omdurman in Sudan between British and Mahdist forces in 1898, and the naval battle between Japan and Russia in the Tsushima Strait in 1905. To be sure, these are familiar landmarks and his account of each is clear, persuasive, and without surprises. But by waiting so long to acknowledge the First Industrial Revolution in warfare, he overlooks critical changes in weapons not just of the eighteenth but also of the early nineteenth century, including explosive shells, steam-propelled iron warships, and supply systems capable of supporting campaigns across indefinite distances by sea.
His most pregnant paragraphs in this section appear as an afterthought to his discussion of the Battle of Königgrätz:
Within days of Königgrätz, every army in Europe was rushing to buy its own breech-loading rifles, many of them superior to the thirty-year-old needle gun. Four years later, when Prussia went to war against France, its infantrymen were at a disadvantage in small arms.... Just as Austrian infantry had been slaughtered charging Prussian rifles in 1866, so Prussian infantry was slaughtered charging French rifles in 1870. Prussia prevailed anyway, ironically enough, because of its artillery.... Having seen that muzzle-loaders were outdated, the Prussians scrapped them after 1866 and reequipped their entire force with Krupp's breech-loading rifled cannons made of cheap and durable cast steel. France continued to rely on old bronze muzzle-loaders. Better artillery gave Prussia a crucial edge in 1870 that allowed its gunners to annihilate the French army from long range.
Such technological flip-flops were to become common in the Industrial Age, when plummeting manufacturing costs allowed a state to completely reequip an army of hundreds of thousands within a relatively short period.... In those circumstances it proved impossible for any state to develop and maintain a lasting technological edge over equally sophisticated adversaries.
Nonetheless,
Outside Europe, the new technology enabled the white man to complete his conquest of the world. For while industrialization was leading toward military parity among European states, it was exacerbating the growing disparity between the West and the Rest.
Boot skips over World War I just as he skipped the advances in weaponry and ideological mobilization between 1750 and 1866, although that conflict introduced many new weapons, and raised the intensity of mobilization on the home front to previously unimagined heights. But Boot prefers to make his "Second Industrial Revolution" in military affairs coincide with World War II and emphasizes three innovations—tanks, aircraft carriers, and heavy bombers—by focusing on the defeat of France in 1940, the Japanese attack on Pearl Harbor in 1941, and the American firebombing of Tokyo in 1945.
As always, these narrative chapters are well written and make a good case for the importance of the three new weapons he chose to discuss. At the same time, he recognizes the partiality of his approach, and acknowledges that other innovations—radar, code breaking, amphibious landings, and improvements in older technologies like submarine warfare and industrial production lines—also affected the outcome.
I quite concur with his summing up of "What Produced Victory?" Here are some of his observations:
The Germans outthought their enemies in the interwar period, which is why in 1939–41 the Third Reich was able to outfight the countries of Western and Eastern Europe.... On paper, at least, this gave the Third Reich the potential to compete against the US and USSR.... Japan, too, grabbed a vast empire for itself in Asia that should have given it greater ability to hold its own. Yet by 1942 the US was outproducing all of the Axis states combined. The USSR, too, staged a remarkable recovery...and was soon outproducing Germany....
He continues:
On the whole, however, the Allies pulled off the difficult feat of war management far better than the Axis. Nazi Germany was plagued by the erratic and often irrational decision-making of Adolf Hitler, who fostered an atmosphere of bureaucratic chaos and infighting. While Japan had no single leader of comparable power, it was handicapped by the lack of coordination between its army and navy. The British and Americans, by contrast, set up a Combined Chiefs of Staff Committee that, despite some inevitable friction, capably coordinated their joint war effort....
This underscores a theme running throughout this volume: Having an efficient bureaucracy is the key determinant of whether a country manages to take advantage of a military revolution.... The reason German armies were able to reach the gates of Moscow and Japanese armies the borders of India before being defeated was that the Axis had done a better job of organizing beforethe war. This gave them an important initial advantage that they allowed to slip away through catastrophic miscalculations—which once again goes to show that the early movers in a military revolution are not necessarily the long-term winners.
This last observation strikes me as a useful warning for American policymakers who are dealing with the ongoing "Information Revolution" that Boot dates from the 1990s, which has transformed warfare with high-tech advances such as cruise missiles, computer-guided targeting and navigation systems, and stealth planes invisible to radar. "While much is still murky," he declares, "one impact of the Information Age so far is reasonably clear: Even while decreasing the importance of traditional nation-states, it has given a substantial boost to the American position in relation to that of other states." More particularly, "American weaponry remains at the cutting edge of military developments."
As before, he illustrates this contemporary military revolution with three narrative accounts, this time of US-led campaigns in Kuwait and Iraq (in January and February 1991), Afghanistan (from October to December 2001), and Iraq (from March 2003 to May 2005). Each lasted longer than its predecessor; and the termination of Boot's final narrative was defined not by events in the field but by his publishing deadline. He is suitably ambiguous in appraising the outcome:
The lesson the United States was learning in Iraq was similar to the lesson that other armed forces had learned on other battlefields: a military machine built for one purpose, no matter how superb, could not easily be redirected to another kind of fight. In Spain's case, an armada that might have been well suited for the placid waters of the Mediterranean did not fare as well in the tempestuous seas of northern Europe. In Germany's case, an army built for a blitzkrieg across relatively confined spaces did not fare as well in the vast steppes of Russia. In America's case, armed forces built for conventional combat in the Arabian desert or European plain did not fare as well in the streets and alleys of Iraq.
I found Boot's discussion of his "Information Revolution" disquietingly triumphalist in tone. In a section titled "America's Unparalleled Power" he writes:
In the early years of the twenty-first century the United States enjoys a preponderance of military power greater than any other nation in history.... Today America is rivaled in land, sea, and air power by...no one. Although the dominance of US forces can still be challenged when they come into close contact with the enemy on his home turf, they are undisputed masters of the "commons" (sea, air, space), which allows them to project power anywhere in the world at short notice....
In the Information Age the US edge lies in quality, not (as it did during the Second Industrial Age) in quantity. Both its soldiers and their equipment are among the best on earth.
But what is the use of being able to "project power anywhere in the world" if American soldiers "can still be challenged when they come into close contact with the enemy on his own turf"? And can the US expect to discover and defeat the amorphous groups of people we call "terrorists," whose anger flames more fiercely with every invasion of distant lands the US government undertakes?
Boot's prognosis is unpromising:
Unless the US government can streamline its Industrial Age bureaucracy and become a networked organization, it may find that even purchasing the latest and best technology will not offer sufficient protection against the country's foes.
But turning the US military into what would, in effect, be a network of independent operators could mean relaxing control from the center, and risks turning the US armed forces into a replica of the loose swarm of enterprising and uncontrolled "terrorists" they oppose.
The concluding part of the book, "Revolutions Past, Present, Future," suffers from similar confusion. Boot surveys a great variety of potential changes in weaponry—robots, star wars, ray guns, computer viruses, nanotechnology, and germ warfare. He concludes: "Advances in biologi-cal and cyberwar promise to put even more destructive potential into the hands of ever smaller groups—as does the continuing proliferation of nuclear weapons." Accordingly, the US
needs to place more emphasis on making up for its deficiencies in irregular warfare.... But that doesn't mean that the US can ignore the dangers of major warfighting or the dictates of technological change.... Innovation must be organizational as much as technological, and it needs to focus on potential threats across the entire spectrum, from low-intensity guerrilla wars to high-intensity conventional conflicts.
So, according to Boot, everything must change at an ever-increasing pace and on an ever-expanding scale. He does not say how that is feasible; nor does he ask whether American or any other human society can conceivably sustain such a continuous proliferation of military enterprise and expenditure. Limits surely exist. No government can continue for very long to spend far more than it takes in while relying on foreigners to finance such extravagance by buying its bonds. Yet that is what the US is doing today. Moreover, aggressive wars like those Americans have been fighting on and off ever since 1955 in Vietnam, Afghanistan, and Iraq inflame opposition both at home and abroad. Surely, if changes of policy fail to diminish such fighting and to check the US government's increasingly strenuous preparation for future wars, a general economic and social collapse like that which overtook the USSR is more likely than the indefinite expansion of our military establishment that Boot foresees.
Had he looked more closely at how French efforts to spread liberty and equality among neighboring Europeans backfired between 1793 and 1815, his observations about the future of our "war on terror" might have been more persuasive. More generally, if he did not assume that technical advances in weaponry, together with appropriate modifications of command and control, guarantee success in war, his understanding of the past and future of warfare would be more plausible.
Overall, I feel that Boot's focus on four separate and distinct military revolutions since 1500 is misleading. Change is pervasive and continual. Fixing on a few periods and aspects of military innovation, as he does, imposes far too tight a corset on the sprawling confusion of human affairs. By schematizing his story so drastically, he minimizes surprises and almost entirely overlooks the larger human setting—moral and intellectual as well as social and economic—within which wars are fought. Professional fighting men are not wholly autonomous and the perpetual social flux within which they, like everyone else, actually exist needs always to be taken into account when trying to understand their victories and defeats.
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Many positive environmental benefits are associated with organic agriculture, however, nutrient losses in the form of leaching and greenhouse gas emissions can still occur from using organic fertilizers. As with any fertilizer, achieving a high nutrient use efficiency (NUE) is central to avoid negative environmental impacts from nutrient export. Increasing NUE and reducing total inputs of agricultural reactive nitrogen (N) has been proposed as key indicators to measure progress towards meeting a number of UN Sustainable Development Goals (SDGs). In many agricultural systems, including ones under certified organic management, N is often a limiting nutrient, and is required to optimize yields and meet crop growth standards. Supplying N in organic cropping systems can be rather challenging due to the variations in availability of N from different sources, including different cover crop species, compost and/or plant and animal waste materials in liquid or solid form. These uncertainties associated with supplying crops with N in organic systems can increase the risk of losses to the environment. Here, we seek to better understand the influence soil edaphic factors have on N release from high N organic fertilizers and clarify how these fertilizers impact or are impacted by the soil microbial biomass carbon (Cmic) pool.
High N containing animal-waste derived fertilizers can supply N quickly and effectively, granting growers application flexibility that can be rare when using other non-animal waste organic fertilizers. Blood meal, feather meal, fish meal and seabird guano, all high N containing certified organic fertilizers with low C/N ratios (< 5), were incubated for 60-days under aerobic conditions, and sampled at 0, 3, 7, 14, 28 and 60 days. Two soils under organic management with different soil textures – high and low clay content – were compared. After application of organic fertilizer at 250 mg N kg-1 soil, net N mineralization rates (Nmin) were measured. A standard non-linear kinetic model was fit to Nmin data in order to evaluate the N release dynamics under incubation conditions. Additionally, to assess the impact of these amendments on Cmic and to determine whether Cmic size had any mediating effects on Nmin, chloroform fumigation-extraction was used to measure Cmic at time points 0, 3, 28 and 60 days. We hypothesized that Nmin will vary by soil type, showing higher Nmin within the soil containing higher clay content, and that Cmic will increase in both soil types with the change in Cmic partially accounting for this variability in Nmin.
Our results did not support the hypothesis that Nmin would vary according to soil type or increase in Cmic. Soil type exerted only a minor influence on Nmin at day 14 of the incubation and organic fertilizer type also only accounted for a small amount of the variability in % of the organic N (%Norg) mineralized after 14 and 28 days. The amount of amendment Norg mineralized over the entire incubation period ranged from -17.74 % Norg at day 3, to 52.96 % %Norg at day 60 in the sandy soil. The modelled Nmin parameters were used to estimate mineralized Norg from the fertilizers. The highest mineralization potential (N0) value of 96.45 mg N kg-1 soil was found for blood meal, which had a very low maximum %Norg. Seabird guano had the highest mean Cmic at 814.82 mg C kg-1 soil. The Cmic levels in all the organic fertilizer treatments fluctuated throughout the incubation period but were never statistically different from the control soils. Information from this study shows that growers can supply plant available N (PAN) consistently using these fertilizers but they may not impact labile carbon (C) pools such as Cmic.
|Advisor:||Horwath, William|
|Commitee:||Zhu-Barker, Xia, Geisseler, Daniel, Scow, Kate|
|School:||University of California, Davis|
|Department:||Soils and Biogeochemistry (formerly Soil Science)|
|School Location:||United States -- California|
|Source:||MAI 81/12(E), Masters Abstracts International|
|Source Type:||DISSERTATION|
|Subjects:||Soil sciences, Agriculture|
|Keywords:||Kinetic modelling, Microbial biomass carbon, Nitrogen mineralization, Organic fertilizers|
|Publication Number:||27742201|
|ISBN:||9798645487508|
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Shares are the units into which a company is divided, giving the holder of those shares various rights and entitlements in the company in respect of which these shares are held. In this Legal Insight we will discuss the basic concept of ordinary shares, which give ownership in a company to the holder of those shares.
A share is a whole unit and cannot be held in fractions. Accordingly, if there are various shareholders in a company, rather than dividing all of the authorised shares in equal parts and sometimes ending up with a fraction of shares, business owners can issue the required number of shares to enable each shareholder to hold an equal number of shares. These issued shares will constitute 100% of the issued shares in a company – with each shareholder holding a percentage of that company’s share capital.
To take a step back, what are issued shares and how are they different from authorised shares? Authorised shares are the number of shares that a company is legally allowed to issue. As an example, when a company is registered with the Companies and Intellectual Properties Commission (CIPC) – a certain number of shares, i.e. one thousand (1000) shares, will be authorised by notice to the CIPC. The authorised share capital (this can be any number) must then be reflected in the company’s memorandum of incorporation.
To continue with the example – of those 1000 shares, the company can issue any number of those shares to its shareholders in exchange for funds, which will constitute the issued share capital of the company. i.e. the company can issue 100 shares to the shareholders or 1000 shares to the shareholders. It is important to note that a company can never issue more than the authorised number of shares. As an example, of the 1000 authorised shares, a company can never issue 1100 shares, because only 1000 shares are authorised or “allowed” to be issued.
Should a company wish to increase its number of authorised shares it will need to do so by amending its memorandum of incorporation and providing notice to the CIPC.
In practice, a company will usually only issue a percentage of its authorised shares for various commercial reasons. One of the biggest reasons why business owners do not issue and hold 100% of the authorised shares in a company, is to leave the option open for further shares to be issued to an incoming shareholder or for further subscriptions by existing shareholders (where an investor or existing shareholder pays for some of the authorised shares in the company, this usually results in the dilution of the issued shares).
Keeping some of the authorised shares in reserve would be especially helpful for small business owners looking to bring in an investor at a later stage of their business. Rather than selling the shares that they currently hold in their business for a profit (which sale can have its own tax implications for the small business owner), small businesses can have the investor subscribe for new shares in the Company.
This is a basic overview of the concept of shares with basic examples of how they can be used as a commercial tool. Contact us for a more in depth discussion about structuring your company’s share capital to maximise your business’ potential. | https://tumboscott.com/2018/07/11/the-basics-ownership-of-a-private-company-and-the-concept-of-shares/ |
May the Lord, who has begun so much good in you this Lent, bring it to fulfillment when the time is right!
Your friend in Christ,
Father Martin
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Praised be Jesus Christ! For those of you who read the Catholic Life magazine from cover to cover, you may recall Bishop Callahan quoting the Eastern philosopher Lao-tzu: “A journey of a thousand miles begins with a single step.” It’s a great quote because of the reality that the end depends upon the beginning. For Christians, the hope of an eternal Easter is in part contingent on how well we lived our Lent. And Lent is a journey, one that sees us striving to move toward greater freedom in our heart to love and obey God and to treat His people as He treats us. Some have likened Lent to a spiritual road trip, an image that may seem to be at least a thousand miles long. An article I came across recently spoke to a similar spiritual journey, one that involves a future priest’s desire to visit as many of the world’s basilicas as possible. Did you know that there are 1,760 basilicas in the world, 84 of them being in the U.S.? The author has already visited 190 of them, including all 24 in Canada and all but 5 of the American basilicas. Something about his goal and his dedication causes one to reflect on his motivation; i.e. why does he want to visit all of these churches? One motivation has to be beauty and that is something we grasp instinctively. People travel all the time to see something beautiful, and we’re deeply affected by these experiences. While truth sometimes fails to convert us, and goodness can be a threat to our insecurities, beauty is the one reality that almost universally touches us where we’re most vulnerable. Lent is meant to be a spiritual journey that moves us ever closer to the Source of all that is beautiful. Prayer, fasting, and alms giving have long been the means that open the eyes of our hearts that we might more and more see what God sees and marvel at its glory. The old Latin maxim was nascantur in admiratione – “let them be born in wonder.” The life, death, and Resurrection of Jesus are the most beautiful and inspiring moments in the history of the world, but only the eyes of deep faith can experience this. All the more reason to live more fully the sacrificial nature of Lent, as it prepares us to taste and see the goodness of the Lord. Visiting basilicas could be no more than an architectural adventure that will ultimately fail to move us spiritually closer to the Lord. Or it could be a tangible living out of the spiritual pilgrimage that is the whole point of our earthly existence. For those who are home bodies, the life of Flannery O’Connor might be more your speed. She was a Catholic author who died of lupus at the young age of 39 in 1964. Though she travelled but very little, her greatest adventures were lived out in her imagination and in her books. Whatever our limitations might be, that part of us is almost always accessible and Lent is an invitation to go deeper into our soul so as to encounter God and rest with Him there. O’Connor had remarkable faith and it proved its beauty by allowing her to carry her cross with courage and to find God in her suffering. O’Connor had heavenly help from the Archangel Raphael, as she said the following prayer every day of her life: “O Raphael, lead us toward those who we are waiting for, those who are waiting for us. Raphael, Angel of happy meetings, lead us by the hand toward those we are looking for. May all our movements be guided by your Light and transfigured with your Joy. Angel, guide of Tobias, lay the request we now address to you at the feet of him on whose unveiled Face you are privileged to gaze. Lonely and tired, crushed by the separations and sorrows of life, we feel the need of calling you and of pleading for the protection of your wings, so that we may not be as strangers in the province of joy, all ignorant of the concerns of our country. Remember the weak, you who are strong, you whose home lies beyond the region of thunder, in a land that is always peaceful, always serene and bright with the resplendent glory of God.” So, whether your journey of a thousand miles be in the world or into the depths of your soul, it goes better with help from above.
May the Lord, who has begun so much good in you this Lent, bring it to fulfillment when the time is right!
Your friend in Christ,
Father Martin
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The term semiosphere [from Greek sēmeion ‘sign’ (sēma ‘mark’) + -sphere] was originally introduced in 1984 by Yuri Lotman to denote space within which constantly function and emerge processes of signification.
In the reality of the semiosphere, the hierarchy of languages and texts, as a rule, is disturbed: and these elements collide as though they coexisted on the same level. Texts appear to be immersed in languages which do not correspond to them, and codes for deciphering them may be completely absent. Imagine a room in a museum, where exhibits from different eras are laid out in different windows, with texts in known and unknown languages, and instructions for deciphering them, together with explanatory texts for the exhibitions created by guides who map the necessary routes and rules of behaviour for visitors. If we place into that room still more visitors, with their own semiotic worlds, then we will begin to obtain something resembling a picture of the semiosphere.
Later in his studies, Lotman continues to explore the concept of the semiosphere, arguing that all semiotic systems function in a semiotic space and a sign would not make sense unless in a context of other signs.
Coined by Lotman the concept Semiosphere gradually started inhabiting and serving many other fields, biosemiotics included.
The semiosphere is a sphere just like the atmosphere, the hydrosphere, an the biosphere. It penetrates to every corner of these other spheres, incorporating all forms of communication: sounds, smells, movements, colors, shapes, electrical fields, thermal radiation, waves of all kinds, chemical signals, touching, and so on. In short, signs of life.
Every organism on Earth is tossed at birth into this hemisphere, to which it must adapt correctly if it is to survive. In the recent decades we have become increasingly aware that everything in this world is connected.
In a way, we live in a continuum of significations, meaning and sense making. We constantly create and read patterns, code and decode signals. Signs and symbols surround us from the very beginning of our life. Some of them we consciously process and use, many we don’t understand and therefore are unaware of.
But what exactly is a sign?
The study that keeps trying to answer what signs and symbols are and at the same time deal with their interpretation and perception is called semiotics. The process of signification is called semiosis.
Throughout times, the question about the sign and its role in culture has been approached by a number of schools of thought (ref. Semiotics for Beginners Daniel Chandler). Various discourses try to hold within the definitions, differentiations and descriptions of what the sign is. One can easily get lost, trying to name (i.e. to formalize) live processes and freeze them into a word.
To be or to signify?
Does the sign transcend what it denotes, does it acquire new connotations, apart from the denotation functions it has. More generally, what is a sign and what is not a sign? (cf. What is Semiotics, by Eugene Gorny).
A note: I took this picture several years ago in Zagreb. Apologies, if this is in anyway inappropriate. After thinking a lot about whether I should hide one of the words, I decided to take the risk and just leave the sign the way it was originally “read anew”, because I find that really important.
A way out of the vicious circle where the understanding is trying to understand itself is to look at signs as signals which lead to action. When entering the vast lands of semiotics it help to always remember that nothing is absolute and we are at all times part of several processes going on simultaneously.
The seeds of these ideas were planted in a talk prof. Bogdan Bogdanov gave during the discussion of his latest book Text, talking and understanding (the link is to a brief English description of the edition).
means to do and say one and the same thing in various ways which then would complement its variations in the acts of a human or a group of humans but as well as in the acts of other humans and groups of humans. | http://www.teodorapetkova.com/thing-finding/semiosphere/ |
FEBRUARY 17, 2020, New York — A Ludwig Cancer Research study has identified a mechanism by which regulatory T cells, which suppress immune responses, adapt their metabolism to thrive in the harsh microenvironment of the tumor. This mechanism, the study finds, is exclusively engaged by regulatory T cells (Tregs) that reside in tumors and could be disrupted to selectively target such Tregs and boost the effects of cancer immunotherapy.
“It has long been known that the Tregs found in tumors protect cancer cells from immune attack, so countering Tregs would be an important strategy for cancer immunotherapy,” says Ping-Chih Ho, associate member of the Lausanne Branch of the Ludwig Institute for Cancer Research, who led the study. “But a major hurdle to such interventions is that the systemic suppression of Treg activity can cause severe autoimmune reactions. We have discovered a potential approach to overcoming that problem, one that selectively targets Tregs in tumors and could therefore prevent such adverse effects.”
Tregs play a critical role in healthy tissues, where they prevent autoimmune disease and aid wound-healing. But, when recruited into tumors, Tregs also thwart anti-cancer immune responses—and immunotherapy. The current study, published in Nature Immunology, identifies a protein that drives the metabolic adaptations of intratumoral Tregs. The researchers show in a mouse model of melanoma that targeting that protein with an antibody significantly boosts the efficacy of immunotherapy without causing autoimmune side effects.
The cores of tumors are often acidic and starved of oxygen and vital nutrients, which forces resident cells to adapt their metabolism to survive. Ho and graduate student Haiping Wang suspected those adaptations might also reveal vulnerabilities unique to intratumoral Tregs. To find those vulnerabilities, they analyzed a dataset of Treg gene expression in breast tumors and blood compiled a few years ago by the laboratory of Ludwig MSK Director Alexander Rudensky.
They found that those and other intratumoral Tregs expressed high levels of genes involved in lipid uptake and metabolism—particularly CD36, a receptor involved in lipid import. An analysis of Tregs from human melanoma patients conducted by Ludwig Memorial Sloan Kettering (MSK) researchers Taha Merghoub and Jedd Wolchok yielded similar results.
To explore the role of CD36 in intratumoral Tregs, the researchers generated mice that lacked the CD36 gene only in their Treg cells and engrafted them with melanoma. “We found that the tumor burden was reduced in CD36-deficient mice,” says Wang, “and the number and functionality of Tregs declined only within tumors, not in the other, healthy tissues of the mice.”
CD36 deficiency induced in intratumoral Tregs a form of cell suicide known as apoptosis that was driven by a decline in the health and number of mitochondria—the power generators of cells. Further study revealed that CD36 fuels the activity of PPARβ, a protein essential to the genesis and function of mitochondria.
Treating mice bearing melanoma tumors with an antibody to CD36 resulted in a decline of intratumoral Tregs that was not seen in genetically identical control mice. When this antibody was combined with an immunotherapy known as PD-1 blockade, which stimulates a T cell attack on cancer cells, tumor growth slowed significantly, prolonging the survival of the mice.
“By targeting CD36 with an antibody, we don’t just create trouble for intratumoral Tregs, we also create trouble for the tumor’s ability to maintain an immunosuppressive microenvironment and hamper immunotherapy,” says Ho.
Ho’s lab is now working to translate these findings into a potential cancer therapy while exploring how CD36-targeting might be combined with other interventions to more extensively disable Tregs selectively within tumors. They are also exploring which other types of solid tumors harbor Tregs that are dependent on CD36 for survival.
This study was supported by Ludwig Cancer Research, the Swiss Cancer Foundation, the Swiss Institute for Experimental Cancer Research, the European Research Council, the Cancer Research Institute, the Society for Immunotherapy of Cancer, the US National Institutes of Health, the Research Foundation—Flanders, the Swiss Cancer Research Foundation, Swim Across America, the Parker Institute for Cancer Immunotherapy and the Breast Cancer Research Foundation.
In addition to his Ludwig post, Ping-Chih Ho is an associate professor at the University of Lausanne. | https://www.ludwigcancerresearch.org/news-releases/targeting-turncoat-immune-cells-to-treat-cancer/ |
https://www.eduzhai.net International Journal of Brain and Cognitive Sciences 2017, 6(4): 74-79 DOI: 10.5923/j.ijbcs.20170604.03 How Does Social Media Affect Health Communication? Leila Habibi1, Hamid Reza Farpour2,*, Razieh Pirzad3 1University of Applied Sciences and Technology, PhD Candidate of Media Management, Department of Media Management, Faculty of Management, University of Tehran, Tehran, Iran 2Assistant Professor of Physical Medicine and Rehabilitation, Bone and Joint Diseases Research Center, Department of Physical Medicine and Rehabilitation, Shiraz University of Medical Sciences, Shiraz, Iran 3Student Research Committee, Shiraz Geriatric Research Center, Department of Physical Medicine and Rehabilitation, Shiraz University of Medical Sciences, Shiraz, Iran Abstract In this paper, we examined the role of social media in health communication using documentary method and netnography in a descriptive-analytical evaluation. Over the past two decades, the Internet has made a paradigm shift in business activities that led to the development of numerous technologies, such as Web services and applications for companies. The majority of health institutions do not have appropriate infrastructure to take advantage of the capabilities of this new technology. The reason of which is primarily the fact that health care greatly relies on face to-face interaction between the patient and physician. Advances in the Internet technology and social media have allowed sharing information remotely in different geographical regions and facilitated health care. Different terms have been presented for doing health care practice, such as E Health, online health, cyber medicine, and consumer health informatics so that these systems have improved the patient care performance, reduced costs and improved workflow. So, social media should be a part of health system programs provided to people through needed information; also, they can be used to make social relationships between groups with common characteristics and reduce stress caused by chronic diseases and patients’ behavior change. Keywords Communication, Health, Social network, and social media 1. Introduction Prior to the adoption and widespread acceptance of the Internet as a source of health information, people received health information from many sources of information such as the physician, family members, acquaintances and mass media. Since 2000, the dependence of people on the Internet search engines has been increased, because the search engines have allowed access to all the web pages around the world. So it can be said that we live in a time of expansion in access to health information. Data that previously could be obtained by spending hours researching medical libraries, all can be readily found by Internet access. Thus, the ability to acquire extensive knowledge of research findings from many different medical specialties has been increased. However, medical specilists are not the only people who search the Internet for such information. Also, patients have the ability to search a medical topic entirely via the Internet. The results of research indicate that the use of social media in America has been increased from 8 percent of adults in 2005 to 67 percent in late 2012 and to 72% in 2013. * Corresponding author: [email protected] (Hamid Reza Farpour) Published online at https://www.eduzhai.net Copyright © 2017 Scientific & Academic Publishing. All Rights Reserved So, new technologies in the form of the Internet use affect the health environment, and patients are increasingly using the Internet both as a source of information and psychological support. Healthcare information for which patients are looking on social media and the Internet are different. The important point is that most people who are interacting with online health care seek to fulfill the unmet need that is either information or support. Regarding these characteristics, we can use the potential in a positive direction by carefully studying and identifying the functions of social media and their effect on audience. One area that seems to have the potential to use the social media in different areas is the field of health; in this paper, we made an attempt to examine the functions of social media for health information researchers. 1.1. Theoretical Principles Research on social media sites has been increased exponentially in recent years. Scientists have conducted studes in a variety of fields on consequences of social media sites in human, moral, social and medical fields. Now, we are not only in the information age, but we live in an age of interactivity that creates abundant opportunities for multiple areas including health education and healthy behavior to change the health behavior. Due to easy access, providing information in audiovisual International Journal of Brain and Cognitive Sciences 2017, 6(4): 74-79 75 and interactive formats and links to navigate to other related Web sites, the Internet is an ideal environment for the dissemination of health information to the public. Online forums are a rich source of data that provide many opportunities to explore real-time interaction on the issues that are important to people. It seems that the Internet can be an important source of providing information about the medical and psychological issues related to diseases and their treatment. By using the Internet, we can not only change the patients' image about their health, but also follow behavioral health changes. So, online information collection can lead to greater patient interaction in their health and maintenance. Internet-based intervention, called ayntrapy, is also economically affordable, since access to the therapist is not possible for all the people; on the other hand, some people, such as those who have agoraphobia, may not be able to leave the house and pass long distances. The Internet treatment programs can be used in this area. On the other hand, educational function of the virtual sites can also be useful for patients. The purpose of patient education is to help improve the quality of life, promote physical and mental health, and boost their self-esteem. Patient health education encompasses all educational activities related to the patient, including healthcare education and clinical health promotion done to help the patients make informed decisions about his disease and acquire self-care skills. The participation of patients and the community in health through educating patients and caregivers leads to increased satisfaction and trust of clients, reduced anxiety and emotion of patients, more understanding of individual needs, specialists' positive and better relationships, and lasting and positive impacts on health. Patient education can reduce the treatment costs greatly through helping patients to manage chronic conditions of the diseases. The use of effective educational materials for patient education contributes to understanding the complexities of medical processes for the patient and reducing the level of stress and anxiety. Educational sources have the ability to make the communication practical and improve health. Increased knowledge of the patient can develop treatment outcome of acute and chronic diseases. For example, in the event of a disease, people are motivated to seek treatment and follow it. Although the Internet has great potential for public education and convenience for patients, in some cases spreading misleading or even fake information actually leads to poor medical care. As a result, websites can be powerful sources for education; on the other hand, because the information is widely available, some patients with the impression that all sites are equal may obtain misleading or incorrect information. More over, the information obtained from the Internet may be in conflict with the advice provided by physicians, thus leading to confusion and uncertainty in patients. The consequences of this uncertainty may be a delay in treatment and/ or inappropriate treatment forms. Dominick et al. (2009) noted that studies have shown that computer programs and web-based health education have been successful to improve knowledge, health and management of a disease. For example, using the Internet helps to understand the cancer patients' better health outcomes and also reduce medical uncertainty and depression. For patients with breast cancer, the Internet has resulted in reducing loneliness levels, increasing social support and helping them to participate more actively in their health care decisions. Similarly, web-based tools used to care the patients with asthma, support decision programs about prostate cancer, and diabetes patient education have assisted in improving knowledge and understanding of the disease. In this type of online interventions, the purpose is to increase knowledge of the disease or health behavior change. In addition, online interventions should be submitted at an understandable level for all people at different cultural and literacy levels. So, today health care is changing and the Internet has been turned into a mass-expanding body of information and now with the increase in health-related information via the Internet (e.g. e-health), health-based organizations should follow standardization and make the words understandable to the public. In the healthcare ecosystem, there are many ways to use and share digital health data, with the help of the Internet as a reliable and safe means. Various terms have been proposed for doing such health care practice such as eHealth, online health, online medical and consumer health informatics. The systems have improved the performance of patient care, reduced costs, and improved workflow. Online management of health care refers to all activities that facilitate health care provision and management using data electronic transmission, storage and retrieval, through the Internet primarily in a private and secure environment. Social media, as a sub-branch of the Internet and virtual media, facilitate sharing health information between users and create new knowledge formed through personal experience. Social media can provide an important space for people with the disease to assiciate, participate in activities, and improve efforts for resistance against complications of the disease. Applications such as blogging now contributes to facilitating the patients' changed role in which patients increasingly are present both actively and specifically on the disease and treatment through online search and share of health information in interactive networks. It seems that physicians encourage these activities and welcome patients as partners in health care. People with active disease in social media are often known as powerful citizens in the technology actively in self-care program. Today, social media function in the field of social health has been increasingly considered by health policy-makers and planners. Social media according to the capabilities can contribute to the formation of effective health communication, media should be a part of health system programs through which the required information is 76 Leila Habibi et al.: How Does Social Media Affect Health Communication? provided to people. It seems that we can use these tools in order to make social relationships between the groups with common characteristics and reduce stress caused by chronic diseases and behavioral changes for patients. Thus, according to the specific capabilities of social media, in this study we made an attempt to identify the functions of social media in health communication. 1.2. Research Background As a source, the Internet is potentially a much better response than the usual care to the patient's needs for autonomy, competence and communication. Anonymity and ease of access at home and at any time caused more support in terms of independence by removing geographical, temporal and financial boundaries. A rich variety of information and support tool (e.g. consulting, treatment planning, and changed behavior support) can provide a wide range of appropriate support and make the patient able to control his state. Aware patients may ask better questions, more effectively manage their disease, and even monitor and intervene to improve their health. Chat groups may help prevent the disease and social support as an alternative; also, common networks may change their disease process. For someone living with a chronic disease, having extensive information is necessary. However, information provided by health experts can sometimes be scattered, inconsistent and random, so that when patients find out the advisors do not have enough time to answer their questions, their information need can be met by contact with relevant support forum or through online support forums. Health advocacy groups are voluntary organizations made aiming to help, advise, provide friendship and emotional support to patients, caregivers, and patients' families. The service groups provide the possibility of contact with other people with similar chronic disease, trust and access to a wide range of practical information. Many health support groups have now made their websites according to their special conditions which provide access to many services, valuable information and direct support with no need for the people’s presence. social media can influence the people, control and support them. In general, the function of media in the field of health has been proven in many studies; according to a global release, the use of the media and public education can play an essential role in the prevention of different diseases and increase public health of the community and "life expectancy". Media have two effects on human: they are both capable of imposing severe psychological distress and inversely reduce one’s stress. On the other hand, virtual social media can provide acceptance or change of health behavior, and social and emotional support for the public. Also, discussions on medical and health problems are provided through the media and due to cultural limitations we cannot talk about them. Diaz et al. (2002) in their paper made an attempt to find out how many people obtain medical information through the Internet and if they trust in the obtained information. The study results showed that at least 27% of people use information available in the Internet on diseases or drugs and most of them trust in such information. Ziebland et al. (2004) conducted a study to discover how men and women with cancer use the Internet through a qualitative study, using a semi-structured interview. Respondents were interviewed across the UK during 2001-2002. Participants were 175 men and women aged 19-83 years, with one of the five cancers (prostate, testicular, breast, cervix, or bowel) and in various stages of treatment and follow-up. The results of the interviews showed using the Internet has been reported, either directly or through friends or family, widely by patients at all stages of cancer care, from initial research to follow up after treatment. Patients use the Internet to find ideas, support and use other people’s empirical information, interprete the symptoms, search for information about testing and treatment, help to interpret the advice, ask questions from physicians, ask anonymous private questions, and raise awareness about their cancer. A study was conducted by Seale et al. (2006). In this study, a new method was used, analyzing adaptive keywords in 97 interviews in 2 Internet-based support groups to compare those with cancer. Seale et al. considered web forum as a rich source of information on experiencing the disease and gender differences and stated a significant difference in gender function. They found that men with prostate cancer use the Internet to search information but women with breast cancer seek social and emotional support, and their concern is the effect of the disease on most of the cregivers. This study indicated that although web forum has in fact a public and observable action, it seems both genders use it as a relative private space to share personal information experienced. In a study on several countries that use information technology and education level, it was found that as literacy skill level of people is increased, perceived usefulness of computers, diversity and intensity of the Internet usage is also increased. This study has shown that people with limited literacy skills have less knowledge to control the disease and heath enhancing behaviors; also, people have shown poorer health state and it is not likely that they use preventive service to those with moderate or high literacy skill. Leimeister et al. (2008) in their paper examined whether online communities potentially make an environment for patients to overcome the disease through social support? This paper’s purpose was to develop and test the efficiency of forming virtual relationships in virtual communities for patients with cancer. Data were collected through a survey of 301 patients with cancer in a virtual environment. In this study, they concluded that virtual relationships for patients play an important role in meeting social needs. Feeling support and information share through the virtual relationships helps the patients cope better with their disease. Høybye et al. (2010) in another study examined social and International Journal of Brain and Cognitive Sciences 2017, 6(4): 74-79 77 psychological characteristics of Danish cancer patients who used the Internet for support. In this study, they invited 230 patients with cancer participating in a public rehabilitation program to participate in an Internet program including education of information retrieval related to cancer. In this study, 47% of the subjects were motivated to join the Internet. By studying the group compared with those who had no incentive to join the group, the results showed that no significant difference was observed between the two groups in terms of life quality and mental health while preventing the disease is relatively related to participants in the Internet support groups. Huang et al. (2012) in their paper examined the patients' tendency to use interactive media to find information related to treatment, surgery, etc. Using 242 patients' opinons through Delfi technique, they concluded that patients prefer access to hospitals' health service through social media. 2. Method Due to limitations of research methods such as interview and questionnaire, they are not capable of assessing the people’s actual experiences and emotions; however, in the recent years, using ethnography has contributed to understanding their emotions and behaviors. In the late 1990s, by introducing netnography to study online communities by Kozinets the researchers widely adapted and developed ethnographic methods based on reflective narratives published online, and they considered it as a new qualitative research method, compatible with ethnographic research techniques which study the cultures and communities emerging through computer-mediated communication. Netnography has 6 steps, some of which overlap: 1. Research Design 2. Login to the field 3. Data collection 4. Commentary 5. Ensure compliance with ethical standards 6. Research. Also in this study, in addition to the use of descriptive-analytical method to understand the topic, netnography has been used to discover social media aspects to help the patients to understand the topic. Netnography is widely used as a research method in online researches; in Iran a few studies have been conducted in this field, so this contributes to a new standard set of conducted research in this field. To log in to Google, we searched a combination of the following keywords websites appropriate for this study: "Health", "Forum", and "Patients". As a result, plates, pages such as http://www.msworld.ir and http://forum.iransalamat.com were found. The second stage includes data collection. In this study, through the direct copy of the comments of the members of the online community on the sits' news, the data were collected. In data collection, especially on the experiences and comments of members, it has been tried to consider the relevance and completeness. The selection process is shown in Table 1. Table 1. The names of selected sites and number of comments The Selected Site adress http://www.msworld.ir http://forum.iransalamat.com items papers comments papers comments Number 10 40 15 50 In this study, data were analyzed simultaneously with collection by quanlitative content analysis by data constant comparison. Data were collected and analyzed regarding the study purpose, i.e. understanding social media aspects in health communication at 6 stages of 1- The researcher’s familiarity with data, 2- Generation of initial codes from data, 3- Search to find themes by a review of different codes extracted in the previous steps, 4- Review of the themes and re-comparing them to data to ensure the accuracy 5- Defining and naming themes and 6- Preparing the final report. Also in this study, methods were used to ensure the accuracy and reliability of the data, including supervisors' review. In this way, parts of the interview text were sent to several supervisors with related codes and classes to examine the analysis process, and comment on the items' accuracy. To calculate the reliability, two encoders' intersubjective agreement method (evaluator) was used. In this method, the codes that are the same from the perspective of 2 persons are specified as "agreement" and non-similar codes are specified as "disagreement". In this study, the reliability between the two encoders using the formula was 73%, higher than 60%, so the encoding reliability was confirmed. 3. Results The analysis of the netnography of social media aspects in health communication is given as follows. After specifying initial concepts, 390 initial codes were extracted from the total items. The codes after several reviews were summarized and classified based on the similarity and fitness; then after the review and comparison of their inner meaning, the classes were identified as primary themes. Primary themes were named according to their nature, as conceptual and abstract. Thus, the themes showed the nature and aspects of social media in health communication. These aspects include: 1- social support, 2- desire to be encouraged, 3education, 4- notification, and 5- experiences. 1. Social support: Patients and people seeking for health information noted that when attending the forums and interacting with other people, they forget their own problems and diseases; they said when they are not attending the forums, they are subject to isolation and depression. 78 Leila Habibi et al.: How Does Social Media Affect Health Communication? 2. The desire to be encouraged: Patients noted that they are much more motivated for the disease follow-up and health control with respect to interaction with others and obtaining information. 3. Education: The members of these sites express satisfaction with preventive education, but in order to evaluate the efficacy of such education on prevention of some diseases, further studies ae recommended. 4. Notification: One of the most important emerging fields in this study was notification by users; it seems that social media can be a great tool for the implementation of educational programs and information about the health field. 5. Experiences: Online chat room allows the patients to share their experiences of the progression of the disease, their symptoms and overall health status. Patients can connect with those who are experiencing similar conditions, get more information and have better understanding of their health. They can have a real picture of what happens in life with the disease, based on the experiences of others. They can also obtain a clearer picture of the disease progression schedule and know the symptoms as warning signs of exacerbation. The function of social media for patiants is proved in other studies. [25, 26, 27] 4. Conclusions Given that there are a lot of discussions about social media in different fields, this study helps to explain understanding social media aspects in health communication. The findings of this study showed that the patients connecting to health-related sites benefit from these sites for various incentives. In this study, 5 aspects were obtained as the sites' function in health communication. First, the patients as well as those who search about health information stated that when they attend a forum and interact with people, they forget their problems and diseases and stated that in the absence of forums they become isolated and depressed. Second, the patients stated that, getting more informative, they had motivation for the disease follow up and conrolling health after attending the forums. Third, the sites' members were satisfied with preventive education but a separate research is needed for the effect of eduction on preventing some diseases. Fourth, one of the most important emerging fields in this study was notification by users. It seems social media can be a great tool for the implementation of educational programs and notification about the health problems. Finally, online chat room allows the patients to share their experiences on the progression of the disease, symptoms and overall health status. By connecting with those who are experiencing similar conditions, the patients become more informed and have better understanding of their health. They can have a real picture of what happens in life with the disease, based on the experiences of others. They can also have a clearer picture of the disease progression and know symptoms as warning signs of exacerbation. Also, by a descriptive study using library method, different aspects of social media functions were studied; some aspects were consistent with the findings by netnography. For example, Fogel (2002) showed that patients increasingly use the Internet both as a source of information and psychological support. Also, Aitken et al. (2014) showed in US for specific diseases, the social media consider health, care and prevention, health behavior change, lifestyle and health insurance details and 70% of Canadians have used the internet for health information, and 92 percent of them using Google search engine, rather than a health portal have collected health information. Cook (2008) has also stated educational function of cyberspace can also be useful for patients. The purpose of the patient education is to help improve the quality of life, physical health, mental health, and boost their self-confidence. Finally, this study also has its limitations. A large part of medical information with different opinions is available on the Internet fot the patient, so evaluating the quality may be difficult because the reliability of the data cannot be confirmed. And data confidentiality breach may occur; of course, in this study it has been attempted to use public forums that are visible to the public as much as possible. Eventually, the related organizations can apply this study results to plan optimal administration of social media for health issues. Through proper monitoring, they prevent developing incorrect information and use this tool to support, educate, and inform the patients. Also, according to the new research topic the need for further research is necessary in order to complete the literature regarding cultural and economic environment of the country. ACKNOWLEDGMENTS The authors would like to thank the Research Consultation Center (RCC) of Shiraz University of Medical Sciences for their invaluable assistance in editing the manuscript. REFERENCES Hamshahri training center (2013) health communication and and social media. Available at: http://www.hamshahritrainin g.ir/news-3709.aspx. 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GA4GH presents vision, model for genomic and clinical data sharing
In today’s Science, the Global Alliance for Genomics and Health (GA4GH) calls for a federated data ecosystem for sharing genomic and clinical data. The authorship, which includes Heidi Rehm, Anthony Philippakis, Rachel Liao, and Angela Page of the Broad Institute of MIT and Harvard, as well as a diverse team of international leaders in academia, research, medicine, and industry, argues that a common framework of principles, protocols, and interoperable technical systems are necessary to enable responsible and effective data sharing.
GA4GH was established in 2013 to bring the community together to build the tools and establish the standards necessary to achieve that goal. Today, it counts more than 400 organizations and more than 700 individuals in its membership, which spans more than 70 countries.
“These stakeholders are working together across traditional boundaries to create the common framework that will allow us to make best use of the millions of genome sequences that currently sit in siloed databases around the globe,” says Peter Goodhand, GA4GH Executive Director and a member of the author group.
“We live in the information age and it is clear that we must share data to advance science and medicine. The GA4GH brings together many groups and programs around the world to share experiences, build standards and implement successful solutions at a global scale,” said Heidi Rehm, Medical Director of the Clinical Research Sequencing Platform at the Broad Institute and a principal investigator of ClinGen. Rehm also serves on the GA4GH Steering Committee and the leadership team of the GA4GH Clinical Working Group (CWG).
To date, GA4GH has created a toolkit of diverse products, including the Genomics API, which allows disparate technology services to exchange genotypic and phenotypic data, as well as the Framework for Responsible Sharing of Genomic and Health Related Data, which outlines the basic principles and core elements for responsible data sharing. GA4GH has also catalyzed the development of three data sharing projects which aim to illustrate the value of sharing data in real world contexts. These consist of (i) an open-ended approach to sharing data across the Internet (the Beacon Project), (ii) an international collaboration among breast cancer genetics experts (the BRCA Challenge), and (iii) a peer-to-peer network of clinicians (Matchmaker Exchange), which is co-lead by Rehm, Philippakis, and Kym Boycott of Children's Hospital of Eastern Ontario Research Institute.
“To create a learning medical system, we must be able to query data across multiple institutions,” said Philippakis, Chief Data Officer at the Broad Institute, who also serves on the CWG leadership team. “By enabling efforts such as Beacon and Matchmaker Exchange, GA4GH is playing a key role in enabling data sharing around the world.”
In addition to outlining successes, the paper notes a variety of remaining challenges to sharing data across national and institutional boundaries. For example, the membership is currently working on solutions to secure data access while maximizing the scope of information that can be shared, to create tools that are flexible enough to be readily implemented in different knowledge domains, and to establish sustainable funding models that support data curation, hosting, and computation.
"Millions of genome sequences are being generated around the globe, but to gain the full benefits from these data — to advance human health and to prevent and treat disease — laboratory and clinical investigators will need more effective means of access to data, regardless of where the data are stored,” said Professor Harold Varmus of Weill Cornell Medical College, former Director of the U.S. National Cancer Institute, and Chair of the GA4GH Scientific Advisory Board. “The only way to do that is for the global community to come together across traditional boundaries — be they national, institutional, or technical — to create a federated ecosystem that works for everyone. The GA4GH has begun to do that in the projects described in this new report.”
The Global Alliance for Genomics and Health is an international, non-profit alliance formed to accelerate the potential of genomic medicine to advance human health. Bringing together over 400 leading organizations working in healthcare, research, disease and patient advocacy, life science, and information technology, GA4GH Members are working together to create a common framework of tools, methods, and harmonized approaches and supporting demonstration projects to enable the responsible, voluntary, and secure sharing of genomic and clinical data.
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Productive international relationships rest on sustained interaction and understanding between nations and peoples. Culture and the arts have played an enduring role in cultivating such mutual awareness and respect.
But these are no ordinary times. With massive movement of trade, ideas and people, we live in a world that is stressed by the day—politically, economically and environmentally.
So what is the fate of cultural relations and artistic exchanges in this age of anxiety and growing intolerance? Can culture really hold us together in a fracturing world?
Its tremendous benefits over the last two decades notwithstanding, globalization has sharpened societal divides, heightening economic insecurity and cultural anxiety among many people. Of course, the mobility of goods, information and people is nothing new; what is new is its speed, scope and scale in our time.
Some are understandably feeling overwhelmed and exhausted by these changes, as we transition from a primarily mono-cultural existence to an increasingly culturally diverse environment. There is not only a disconnect between the elites and the public, but also a schism within the elites about the nature and merits of trade, migration, and the flow of ideas and ideologies. The rise of assertive nativism and re-nationalization in many parts of the world is due in large part to the negative fallout of globalization.
Adding to these complex dynamics, a crowded, fractured, and transparent information environment has become a part of our daily existence. Popular emotion and public opinion are exerting greater constraints on policies and state actions. The information cacophony in the digital space, with plenty of misinformation and disinformation, has exacerbated our incredulity and distrust. To make matters worse, the excess of political rhetoric through these channels of communication makes the public’s existential fear ever more vivid and visceral.
Cultural contacts, accidental or premeditated, can be harmonious mixing and mingling, but can also be contentious and sometimes even violent.
This is clearly a pessimistic view of the human condition. But Niebuhr was not merely resigned to cynicism or despair. Recognizing our limitations and that there is no escape from societal conflict, he asked, “what can be done to save societies from endless cycles of conflicts?” His answer was forthright—to reduce them to a minimum by expanding social cooperation.
Our task is then to develop the incentive and capacity for cooperative behavior. And the basis of this enterprise is expanding the spaces of collective empathy.
The contemporary movements of trade, people and ideas bring tension into our physical as well as our imagined spaces. Cultural contacts, accidental or premeditated, can be harmonious mixing and mingling, but can also be contentious and sometimes even violent. After all, our tastes and sensibilities are varied, distinct, and may clash. Nevertheless, these encounters should be, to borrow from the late journalist Christopher Hitchens, clashes about (not of) civilizations.
Cultural relations provide the opportunity for us to open up vistas of experiences and to negotiate differences as we confront cultural clashes. The question then becomes: do cultural/artistic exchanges make us better communities and better citizens?
This is both a normative and empirical question. Some view culture and the arts as the consummate form of communication that helps to expand spaces of expression and empathy. On the other hand, as an empirical question, we need to better capture and further understand, for instance, the extent to which cultural exchanges enhance our communities’ cultural, social and civic capital, which we assume, as resources, are crucial for the preservation and vibrancy of local communities in global society.
There is no question that we now have more opportunities than ever to see and experience the world as a foreigner and as an outsider. At the same time, we also look for relief in the face of mounting cultural angst, as an insider and as someone who is being visited upon by others.
As we navigate an increasingly volatile world of extreme tendencies, I see culture and the arts as a moderating force, as they help to release some of the tensions in an evolving international order under great stress, and more importantly, provide us with cultural generosity to better identify and cope with the other.
CPD Editor's Note: This blog is based on Jay Wang’s plenary address at the 3rd Edinburgh International Cultural Summit.
The recent surge of nationalism around the world is not only a reaction against globalized identity, culture, and markets, but a defense of the dualistic myth. Make no mistake, the psychological barricade protecting dualism as a primary way we perceive the world has great immunity against a Trekkian global identity. Samuel Huntington proposed that a “Clash of Civilizations” would define the post Cold-war system, but could the more fundamental foreign policy challenge we face be called a Clash of Imaginations, where the resistance to a globalist identity foments within the dualistic myth we continue to consume and thereby produce though policy? A future of perpetual conflict because we simply fail to imagine a future of cooperation?
It has been said that the world can be divided into two tribes: you’re either a Star Wars fan or a Trekkie. This pop culture partition extends into foreign policy: either you see the the international system as an everlasting galactic battle between the dark side and righteous rebellion, or a steady march towards a multilateral federation boldly going where no one has gone before. If we truly steer in the direction we are looking, the value of identifying a psychological bias towards conflict and dualism is paramount. | https://www.uscpublicdiplomacy.org/blog/cultural-relations-moderating-volatile-world |
"Discoveries and Delights in the Details of a Life"
It is a special pleasure to return to the Cotsen Children's Library today and this gathering of the Beatrix Potter Society. Nearly 3 years to the day I was invited to this same podium to celebrate the publication of the Cotsen catalogue. I could scarcely have imagined how important it would be to my own research, and how much I would rely upon it. So to all those who made that reference work possible, Anne Hobbs, Ivy Trent, Judy Taylor Hough, and the Cotsen staff, again my deep appreciation.
Shepherds and ecologists are butting heads over what’s next for the beloved landscape.
Abbot Hall Art Gallery. The Art of Beatrix Potter 1866-1943. Kendal, Cumbria, England: Abbot Hall, [198?].
Basso, Enid, Knox, Rowena, and Whalley, Irene (eds). Beatrix Potter and the Lake District: Beatrix Potter studies VII: Papers presented at the Beatrix Society Conference, Ambleside, England, July 1996. London: Beatrix Potter Society, 1997.
Battrick, Elizabeth. Beatrix Potter Gardner: An exhibition at the Armitt Museum, Ambleside 22 May- 4 October 2004. Cumbria, England: Armitt Trust, 2004.
Battrick, Elizabeth, Armitt Library, Ambleside Ruskin Library, and Ambleside Book Society. Beatrix Potter: The Unknown Years. Ambleside, U.K.: London: Armitt Library & Museum Centre ; F. Warne &, 1999.
Birnam Arts. Beatrix & Charlie. Dunkeld, Perthshire, Scotland: Birnam Arts, 2014.
Brown, Geoff. Herdwicks: Herdwick Sheep and the Lake District. Cumbria, England: Hayloft Publishing LTD, 2009.
Dalby, Richard. The Golden Age of Children’s Book Illustration. New York: Gallery Books, 1991.
Desmond, Ray. Kew: The History of the Royal Botanic Gardens. London: Harvill Press with the Royal Botanic Gardens, Kew, 1998.
Denyer, Susan. At Home with Beatrix Potter: The Creator of Peter Rabbit. New York: Harry N. Abrams, 2000.
Goldthwaite, John. The Natural History of Make-Believe. New York; Oxford, Oxford University Press, 1996.
Hobbs, Anne Stevenson and Dulwich Picture Gallery. Beatrix Potter: Artist & Illustrator. London; New York: Frederick Warne, 2005.
James, Phillip. English Book Illustration 1800-1900. London; New York: King Penguin Books, 1947.
Jay, Eileen. Beatrix Potter's Manchester Roots and Armitt Connection. Milnthorpe: Beck Publications, 1994.
Jay, Eileen and Hall, Jenny. The Tale of London Past: Beatrix Potter’s Archaeological Paintings from the Armitt Collection Ambleside. London: Frederick Warne & Co., 1990.
Jacobsen, Elaine and Simmons, Veronica. Beatrix Potter Studies, Index to volumes I-VI. London: Beatrix Potter Society, 1998.
Linder, Leslie. The Beatrix Potter Papers at Hill Top. Stroud, England: Ian Hodgkins & Company, 1987.
Potter, Beatrix and Rawnsley, Canon Hardwicke. Peter Rabbit’s Other Tale. London: Beatrix Potter Scociety, 1989.
Potter, Beatrix. The Tale of Gloucester: a facsimile of the original manuscript and illustrations. New York; London: Frederick Warne & Co., Inc., 1968.
Pritchard, J. and Riddle, Brian (eds). Beatrix Potter studies I: Papers presented at the Beatrix Potter Lake District Study Conference, July 1984. Devon, England: Avocet Press, .
Roscoe, Henry E. The Life & Experiences of Sir Henry Enfield Roscoe. London, New York: Macmillan and, Limited; The Macmillan Company, 1906.
Sotheby's London. English Literature, History, Children's Books and illustrations including a Royal Military Library from the House of Hanover. December 16, 2010. [auction catalog].
Taylor, MA and Rodger, RH. A Fascinating Acquaintance: Charles McIntosh & Beatrix Potter: Their Common Bond in the Natural History of the Dunkeld Area. Perth: Perth Museum and Art Gallery, 1995.
Taylor, Judy. Beatrix Potter’s Hedgehogs. London: Beatrix Potter Society, 2012.
Tisdale, Miranda and Scoular, Clive. Dear Mr. Cunningham: Letters from Beatrix Potter to the Right Hon. Samuel Cunningham. County Down, Clive Scoular, 2012. | http://bpotter.com/Research.aspx |
It has been almost 4 years since I was first elected to the city council. These four years have been both immensely challenging as well as immensely rewarding. I have worked hard to be an advocate for both Ward 1 and the City as a whole, to be available and accessible to constituents, and to make decisions based on good data and a thorough vetting among all stakeholders.
A Newton native with two children in the Schools, I have been deeply involved in my community for the last 12 years, including serving as a board member and vice president of the Newton Conservators, and on the Board of the League of Women Voters -Newton. I co-chaired the Environmental Committee for the Newton LWV for several years.
Some of my accomplishments include;
Public Safety
Improved pedestrian safety and accessibility, especially along walk to school routes. This includes adding 4 way stop signs, increasing spot police patrols along walk to school routes, advocating for street redesign that prioritizes safety for all users and working with the Commission on Disability to ensure that curb cuts meet accessibility codes. I also voted to lower the default speed limit city wide to 25 MPH.
Worked with city staff and local activists to advocate for improving pedestrian safety and access at Newton Corner. The $750,000 project is ongoing and scheduled to be completed later this year.
Environmental Protection and Sustainability
Docketed the Solid Waste and Recycling budget resolution which unanimously passed the full city council in last May. Developed a list of action items that moves the City forward on a holistic, cost effective path for managing trash and recycling, including reducing consumption, improving recycling rates, and encouraging re-use and re-purposing of materials and products.
http://newton.wickedlocal.com/opinion/20160519/commentary-newton-should-set-bar-higher-for-recycling.
Recognized as the “2015 Environmentalist of the Year” by the Newton Conservators for work as a dedicated educator and advocate for environmental issues.
Honored by Green Newton for my efforts to phase out thin, single-use plastic bags and encourage reusable bag use.
Co-sponsored an item on municipal aggregation designed both to save rate payers money on electricity rates and encourage the purchase electricity from renewable sources.
Effective Advocacy;
When new toll rates were announced by Mass DOT Newton was the only toll location that showed an increase. In fact, the new electronic toll gantries would have resulted in a fifty percent toll increase (from $1.00 to $1.50) to travel between Newton Corner and Downtown Boston. I testified and sent comments to Mass DOT asking them to reconsider, and the rate was reduced to $1.35.
I advocate for and support our public Schools, and this included voicing my opposition to Question 2 regarding Charter Schools.
http://newton.wickedlocal.com/news/20161026/leary-why-im-voting-no-on-question-2
Public Health -TCE (trichloroethylene) Contamination in Nonantum
Organized three community meetings to date to keep residents updated and informed on the TCE contamination of groundwater in parts of Nonantum. I filed a Public Involvement Plan (PIP) with DEP which requires that the responsible party provide information about the nature and extent of contamination, respond to questions from the community and explain how response actions will be implemented. This issue is ongoing.
Housing and Development;
As a member of the Zoning & Planning Committee I helped craft and voted for the Accessory Apartment ordinance which allows homeowners more flexibility to make changes as needed to stay in their homes.
Going forward my priorities include;
Schools & Public Places
Work closely with the School Committee in support of our excellent schools. Improve and maintain our schools and city buildings, parks and open space, sidewalks and roads, and water, sewer and stormwater utilities.
Zoning, Development & Land Use:
Encourage policies and programs that reduces the dependence on local property taxes and evaluate locations of the city that lend themselves to appropriate commercial and mixed use development.
Encourage diverse housing types that appeal to persons and households from a wide range of economic levels, cultures and age groups.
Optimize land use in village centers with a lively mix of uses, including housing, businesses and shops, civic and open spaces that invite walking, biking and reduce the reliance on auto use.
Foster a strong sense of place: Consider the history, micro-environment and character of communities when planning new development.
Include strategies for maximizing green infrastructure that mimic natural systems in our zoning code. This includes increasing tree and vegetative cover, green roofs, permeable surfaces and utilizing cool pavements. This not only reduces the urban heat island effect, but also reduces storm water runoff and provides public health and economic benefits.
Sustainability, Transportation & Green Infrastructure
Promote regional land use planning and transportation options. Regionalize the responsibilities of growth by coordinating and communicating with neighboring communities.
Connect and expand walk- bike corridors (research has demonstrated that increasing a neighborhood’s “walkability by just 5% is correlated with driving 6.4 % fewer miles per capita). A study by the Urban Land Institute in Cambridge projected that “maximum deployment” strategies to increase walking and biking could reduce CO2 emissions by millions of tons by 2050.
Engage in long and short term transportation planning strategies that prioritize public transit and designs roads for all users. Work with all stakeholders to leverage funding for significant infrastructure improvements that improve access and reliability.
Review and expand current solid waste and Recycling goals annually. Set a goal of a 50% diversion rate curbside by 2022.
PILOTS; payments in lieu of taxes & Tax Policy
The amount of the PILOT should reflect the cost of providing services to a non-profit. Especially the cost of core public services like police and fire protection, snow removal and street cleaning. I would pursue a more formal PILOT agreement similar to what the City of Boston has done, which is to call for voluntary payments based on an institutions tax exempt property value.
Opioid Crises
Like many communities in Massachusetts we are facing an opioid crisis. We had a 140% increase in opioid fatalities – from 7 opioid deaths in 2015 to 17 opioid deaths in 2016. We need to continue to build on the work of the PATH Program (Prevention, Awareness, Treatment and Hope), including prevention programs, outreach and education and addiction recovery services. We moved in the right direction by requiring that all first responders, including the Fire Department and school nurses carry Narcan. Our efforts must be ongoing.
For a more information please visit my website; http://www.alisonleary.com/ or contact me directly at [email protected].
I look forward to serving another term on the city council and I ask for your vote on November 7th. | https://village14.com/2017/07/29/leary-an-effective-advocate-for-newton/ |
Inclusive language ensures the content does not stereotype people based on characteristics like race, sexual orientation, or socioeconomic status.
By prioritising inclusive language in brand content, companies can effectively communicate its values to customers and project a positive image of their organisational culture. Brands must create an inclusive language style guide that helps marketers and other employees identify words and phrases that they must avoid in their official communication materials.
The guide must be tailored to the company’s values and should provide alternatives to the restricted words. Executives and brand leaders must also ensure that they use inclusive language to set an example for others to follow.
Brands must also evaluate past content to identify better alternatives for non-inclusive language. Similarly, given the fluid and ever-changing nature of inclusive language, brands must maintain open and honest communication within the company. They should also encourage employees to share their ideas about how inclusive language guidelines can be improved. | https://today.yougov.com/topics/resources/articles-reports/2022/01/20/inclusive-language-can-help-engage-diverse-audienc |
Good evening,
My mother no longer has her 'original' birth certificate. She has two others, both of which are in my possession and I am having difficulty citing them.
The first one was issued in 1965, I believe she needed it to get married. The original didn't survive, so what I have is a photocopy. Complicating matters is that she was born in Brooklyn, her original birth record was filed in Brooklyn and this certificate was issued by the City of New York.
I have so so many questions...
1. Should I put this together as an artifact or as a local certificate?
2. If I put it together as an artifact - do I use something similar to the model on pg. 105, or something like a local certificate with a layer stating its provenance?
3. Is this a county or city certificate? And what do I use - City of New York, Kings County or Borough of Brooklyn?
I'm guessing its an artifact and City of New York - so this is what I have and I am hoping its close to being right.
Mother's Name birth certifcate no. 00000 (short-form), issued 1965, New York City, citing birth on 17 September 1947; privately held by Hendrickson [address private] city, state. This document is a photocopy of a certificate formerly held by Mother's Name and passed to her daughter, Hendrickson.
The second is a newer certificate, also short form, that she got in 2013, but it provides the name of her parents. She ordered 2 copies and I just recieved one. So again my question is this an artifiact or a city or county certificate?
In case its a local cert. I've put this together, but I don't know if I have it right, since I am unsure of jurisdiction is the city or county level.
New York City, birth certificate no. 00000, Mother's name; Office of Vital Records, Department of Health and Mental Hygeine, City of New York.
I have attached the first one removing any identifying info so you can see.
Hendrickson, if you did not…
Hendrickson, if you did not order these documents yourself so that you know exactly where they came from and under what circumstances—if these came to you as a "family artifact" from your mother—then cite them as a family artifact. You might also want to note that the 1965 document is a "short form" certification of birth rather than an image of the "long form" original certificate. (EE 9.30 and 9.40)
Thank you for your quick…
Hendrickson, my apologies…
Hendrickson, my apologies for the "short form" comment. Somehow I missed that part of your reference amid all the other details.
Regarding your latter questions about jurisdictions within New York, that's a complicated issue--and also one reason why it is best to not try to guess at the location a certificate came from. If you ordered it yourself, you would know the office that provided it. If not, you might surmise wrong. Since you say that you ordered them yourself, your decision about whether to consider them county-level or borough-level would depend upon the office from which you ordered them and received them.
I would like to make sure…
I would like to make sure that I understand this process of providing proper documentation of BMD items.
If the document has a raised seal on it indicating it came for a registry, the source would be the registry listed on the document (i.e., NYC DORIS).
If the document is a copy (photo/xerox/etc.) of a document (even if there is the visibility in the copy of the raised seal, the source is a family artifact.
If the document is available for download online, the source is the service (ancestry.com, myheritage, findmypast) that provides the image. This would also apply to the transcript of a document available online in transcript form.
Is this correct?
Thank you for your help. | https://evidenceexplained.com/node/1769 |
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Binary number: In mathematics and digital electronics, a binary number is a number expressed in the base-2 numeral system or binary numeral system, which uses only two symbols: typically "0" and "1" (one). The base-2 numeral system is a positional notation with a radix of 2.
Binary relation: In mathematics, a binary relation between sets X and Y is a subset of the Cartesian product X × Y; that is, it is a set of ordered pairs consisting of elements x in X and y in Y. It encodes the information of relation: an element x is related to an element y, if and only if the pair (x, y) belongs to the set. A binary relation is the most studied special case n = 2 of an n-ary relation over sets X1, …, Xn, which is a subset of the Cartesian product X1 × … × Xn.An example of a binary relation is the "divides" relation over the set of prime numbers P and the set of integers Z, in which each prime p is related to each integer z that is a multiple of p, but not to an integer that is not a multiple of p.
Binary prefix: A binary prefix is a unit prefix for multiples of units in data processing, data transmission, and digital information, notably the bit and the byte, to indicate multiplication by a power of 2. The computer industry has historically used the units kilobyte, megabyte, and gigabyte, and the corresponding symbols KB, MB, and GB, in at least two slightly different measurement systems. | http://www.englishvs.com/ingilizce-sozluk/kelimeler/ingilizce-kelimeler/b-ile-baslayan-ingilizce-kelimeler/binary |
If you’ve ever been involved in a hiring decision, did you pay any special attention to the competencies and motivation of the applicants? We know that highly skilled and motivated employees will do more, do it better, and be around to do it longer. But have you given as much attention on how to maintain and/or improve employee motivation?
Motivation Defined
Before diving into those factors, I’ll explain what I mean by motivation: Motivation is an energy and passion to do something to either obtain rewards or avoid punishments. Using this definition, everyone is motivated, but the direction and focus of the motivation is what matters. For example, some teenagers spend hours perfecting their dexterity on video games. In this regard, they are highly motivated. However, the same kids have absolutely no motivation to wash dishes.
Why is Motivation Different for Each Person?
We are constantly inundated with choices on how to spend our time and energy. By choosing one way to spend your time, you are in essence choosing not to spend your time in other ways. For example, if I choose to go on a long run on Saturday morning, I am also making the choice not to eat breakfast with my family.
You can better determine which choice and effort a person makes by evaluating these three factors:
1) Performance Confidence – can I do it?
2) Reward Expectations – will I get something for doing it?
3) Perceived Value – how do I value that reward?
As it applies to work motivation, when an employee believes they can perform their job duties, believes a result will come from their effort, and then values that result, they will be motivated. To the extent that any of these factors slips, then other choices may become more motivating (e.g., leaving work early).
Lead Driver
When explaining this concept to others, I like to use an analogy of a road trip where an employee is driving down a road — think of it as a career journey. Driving around familiar streets and neighborhoods is relatively easy, with known sources for moderately fun experiences. However, there is little growth, and the value is limited.
Conversely, taking an adventure to exotic and challenging terrains can yield new experiences and long-term rewards. However, “climbing the mountain” requires more effort and greater risk. This is where a leader can be most effective. Acting as a guide, she gives direction where uncertainty exists and provides support to boost confidence (Performance Confidence), gives signs of progress and keeps the destination in view (Reward Expectation), and ensures that the destination and rewards are important to all parties on the journey (Perceived Value).
The Leading Data
In a recent study of leadership style and employee engagement, we found a number of factors that differentiate effective leaders in terms of motivating their employees:
Employees of leaders who prefer order and structure have 15% higher Performance Confidence as compared to employees of leaders who prefer spontaneity.
Employees of leaders who hold themselves and others accountable have 20% higher Reward Expectations as compared to employees of leaders who make allowances for chance and personal misfortune.
Employees of leaders who are more accepting of employee emotions have 20% higher perceptions of Shared Values with the organization than employees of leaders who discourage personal expressions.
In other words, effective leaders will create environments that promote higher levels of employee motivation. While hiring high-potential individuals is a good start, keeping them at their peak requires paying attention to the factors that affect their motivation. Is there a map to high performance? Is there an obvious connection to reward and success? Are the outcomes personally valued and meaningful? Be aware that there is constant competition for your employees’ attention and that success comes when you can direct that attention to mutually beneficial and achievable outcomes. | http://blog.wonderlic.com/leadership-directions-for-motivation |
In early June, Faith in Older People and the Scottish Partnership for Palliative Care held a joint conference which had the aim of considering the impact of recent policy initiatives in relation to spirituality and palliative care and the extent to which spiritual care is seen as an integral part of person-centred care towards the end of life.
The conference provided an opportunity to consider the policies and their impact on practice in a variety of settings which reflect the integration of health and social care. Delegates had an opportunity to share experiences, to discuss potential for improvement and to identify how such improvements might best be supported.
The integration of health and social care is a key Scottish Government policy aimed at redefining how we deliver services and how we collaborate across professions, sectors and budgets. The conference was set in this context and we wanted to consider the two delivery plans with perhaps embrace the less obvious elements of the process – palliative care and spiritual care. The Palliative Care Framework is being implemented whilst the spiritual care delivery plan is still under consultation.
Both address how we should deliver good person-centred care particularly at the end of life. Perhaps both highlight areas in which there are misunderstandings of what they represent and importantly how they can be effectively delivered and enabled.
Each of these key delivery plans refer to the other – a principle in the palliative care strategy relates to spiritual care and spiritual care is considered in the light of end of life and a rights based approach. They need to talk to each other in order to meet the needs of patients and residents. We need to consider how implementation can encompass training and skills in both sectors; be key elements in providing quality care and be readily understood and put into practice. We need to better ensure that the links are made and the different policy initiatives that come under the umbrella of integration are aligned to ensure proper implementation.
Strategic Framework for Action on Palliative Care and End of Life Care 2016-2021 – The Scottish Government December 2015
National Delivery Plan for Spiritual Care in Scotland 2016-2021 is being consulted upon at the present time – two key elements in the role of spiritual care staff are: | https://www.faithinolderpeople.org.uk/aligning-policy-and-practice/ |
The present invention relates to an ion source suited for ionizing a sample existing in a liquid to introduce the ionized sample into a mass spectrometer, and a mass spectrometer using the ion source.
Using capillary electrophoresis (CE) or the liquid chromatograph (LC) it is easy to separate a sample existing in a solution but difficult to identify the kinds of samples separated. On the other hand, a mass spectrometer (MS) can identify the separated sample with high accuracy. Thus, when it is intended to separate and analyze a plurality of biological substances dissolved in a solvent such as water, there is generally used capillary electrophoresis in combination with a mass spectrometer (CE/MS) or liquid chromatograph in combination with a mass spectrometer (LC/MS) which is constructed by combining the capillary electrophoresis or the liquid chromatograph with the mass spectrometer.
In order to analyze the sample, which is separated by the capillary electrophoresis or the liquid chromatograph, using the mass spectrometer, it is necessary to transform the sample molecules in the solution into gaseous ions, i.e. particles or gaseous materials. A conventional technique for producing such ions is known as the ion spray method (as is disclosed on pp 2642 to 2646, Analytical Chemistry, Vol. 59 (1987)). In the ion spray method, the gas is introduced along the outer circumference of a capillary, and a high voltage (e.g., 3 to 6 kV) is applied between the capillary to be fed with the sample solution and an aperture (e.g., the sampling orifice) for introducing the ions into the mass spectrometer, so that an intense electric field is established at the capillary tip. By the electrospray phenomenon established by that construction, there are produced fine charged droplets, which are evaporated by the aforementioned gas to form gaseous ions, i.e. gaseous particle or gaseous materials. The ions thus formed are introduced via the sampling orifice into the mass spectrometer so that they are mass-analyzed. The aforementioned gas promotes the atomization of the charged droplets and suppresses the discharge at the tip of the capillary.
Another conventional technique is known as the electrospray method of ionizing a solution with no gas flow at a flow rate of 10 xcexcL (i.e., microliters)/min. to the capillary (as disclosed on pp. 4451 to 4459, Journal of Physical Chemistry, Vol. 88 [1984]). The electrospray method is different from the ion-spray method but has the same ionization principle as that of the ion-spray method.
A further conventional technique is known as the atmospheric pressure chemical ionization method (as disclosed on pp. 143 to 146, Analytical Chemistry, Vol. 54 [1982]). In the atmosphere pressure chemical ionization method there is disposed in the vicinity of the tip of the heated capillary an electrode for generating a corona discharge to ionize the volatile molecules sprayed under atmospheric pressure.
The various conventional spray ionization methods described above in order to achieve a high ionization efficiency, it is necessary to form fine charged droplets having a diameter no more than about 10 nm.
In the conventional techniques described above, a high voltage is applied around the sampling orifice. This application makes it necessary to avoid an electric shock, thus causing a problem that the instrument has a complicated structure. Since the high voltage is applied to the capillary tip in the CE/MS, a higher voltage has to be applied so that the electrophoresis of the sample may be effected in the capillary electrophoresis instrument.
Moreover, the electrospray phenomenon is so seriously influenced by contamination at the tip of the capillary and on the surface of the sampling orifice that once the spray of the sample solution is interrupted the electrospray method or the ion spray method detects different ion intensities with a poor reproducibility even if the spray is reopened under the identical conditions. In order to maximize the ion intensity detected, therefore, the troublesome operations of finely adjusting the capillary position or cleaning the capillary tip and the sampling orifice surface are required each time the spraying operation is reopened. As a result, the structure of the instrument is so complicated for avoiding electric shock that the operations are obstructed.
In the conventional techniques described above, moreover, the sample solution has to be mixed with volatile molecules such as alcohol or ammonia as the solvent. It has been empirically known that no electrospray phenomenon occurs when the solvent used has a low electric conductivity, and that the electric conductivity of the sample solution has to be within 10xe2x88x9213 to 10xe2x88x9215 xcexa9cmxe2x88x921 so as to establish the electrospray phenomenon. Thus, there arises a problem that so long as those conditions are not satisfied, the electrospray phenomenon does not stably occur to limit the selection of the solvent.
Further, since a high voltage is applied between the capillary and the sampling orifice, a discharge may occur around the ion source to make it difficult to use an inflammable solvent. If the kind of solvent to be used is thus limited, the substance to be measured may be unable to be separated by the capillary electrophoresis or the liquid chromatograph.
The object of the present invention is to provide an ion source that can be safely and easily operated and a mass spectrometer instrument which is capable of producing ions stably and analyzing a sample with high sensitivity and with an excellent reproducibility by using the ion source.
Another object of the present invention is to provide an ion source, which can use a wide range of solvents in the capillary electrophoresis or liquid chromatograph, and a mass spectrometer instrument using the ion source.
The present invention includes an ion source having an ion source body for forming a gas flow around the outer circumference of the tip of a capillary to be fed with a sample solution, so that the gas is sprayed around the outer circumference of the tip into the air to ionize the sample solution. In the present invention the Mach number is determined by the flow velocity of the gas and its sonic velocity to be at least within a range around 1. Moreover, the ion source body is constructed to have a gas inlet port for introducing the gas and an orifice for spraying the gas, into which is inserted the tip of the capillary so that the gas is sprayed from a small volume formed between the outer circumference and the inner circumference of the orifice. The present invention may alternatively include a mass spectrometer instrument using the aforementioned ion source.
The characteristics of the ion source of the present invention will be described in more detail in the following. The ion source includes a capillary for feeding a sample solution into the air, and an ion source body having an orifice for receiving the tip of the capillary and forming a gas flow along the outer circumference of the capillary to the tip of the capillary. A characteristic value F/S dictating that the gas flow is within a predetermined range is determined by a flow rate F of the gas reduced into the standard state (i.e. standard conditions) (20xc2x0 C., 1 atm) and the cross section of a cross section normal to the center axis of the orifice, whereby the sample solution fed into the air is ionized in the vicinity of the tip of the capillary by the gas flow. The desired predetermined range of the aforementioned characteristic value F/S is 200 m/s to 1000 m/s. In order to ionize the sample efficiently, the aforementioned characteristic value F/S is preferably set to 350 m/s to 700 m/s and more preferably set to 500 m/s to 600 m/s. Here, the value F/S has the same dimensions as those of a velocity but is different from the actual velocity of the sprayed gas. The flow rate F is a value which is reduced from the flow rate of the sprayed gas in the standard state. The actual sprayed gas has a higher pressure than 1 atm. Incidentally, the flow rate of the sample solution is set to 1 xcexcL (i.e., microliters)/min. to 200 xcexcL (i.e., microliters)/min.
By the gas sprayed from the small volume at the tip of the capillary, fine charged droplets of the sample solution are formed at the capillary tip. When the Mach number of the gas flow approaches 1, finer charged droplets are formed. By the sprayed gas, the solvent is gasified from the formed charged droplets to produce gaseous ions, i.e. gaseous particles or gaseous materials. The ions thus produced can be introduced into and analyzed by the mass spectrometer.
When the characteristic value F/S of the sprayed gas flow at the capillary tip exceeds a certain value, the sample solution introduced into the capillary is broken into charged droplets of various sizes at the capillary tip. The extremely fine charged droplets of less than at least 100 nm are easily desolved (or dried). Even the neutral sample molecules may be bonded to protons or sodium ions in the extremely fine droplets to produce quasi-molecular ions so that the ions can be analyzed by the mass spectrometer instrument.
The conditions for determining the size of the droplets to be formed at the capillary tip are essentially the characteristic value F/S or the Mach number of the sprayed gas flow. In the production efficiency of the extremely fine droplets, there are other factors to be considered. In other words, the pressure difference between the solution surface and the volume surrounding the capillary tip has to be larger than a certain value. By reducing the capillary wall thickness to 100xcexc or less, the production efficiency for the extremely fine droplets can be enhanced.
Moreover, the reproducibility of the ionization conditions can also be enhanced by aligning the center axis of the capillary with the center axis of the orifice of the ion source body to make the gas velocity uniform at the tip of the capillary so that the sprayed gas containing the droplets of the sample solution may be axially symmetric.
If the characteristic value F/S of the gas flow is constant, the droplets of the sample solution have substantially the same distribution of their size and have no substantial relation to the gas flow rate F and the cross section S of the small volume for spraying the gas. Empirically, it is sufficient that the gas flow rate F be 0.5 liters/min. or more. The material of the capillary and the potential to be applied to the capillary have no substantial influence upon the size of the droplets to be produced from the solution.
According to the present invention, the ions can be efficiently produced from the sample solution by the sprayed gas while grounding the potentials of the individual portions such as the capillary constituting the ion source to the earth. As a result, the ion source can have its structure made simpler and its operability and safety enhanced better than those of the conventional ionization method. Moreover, when the ion source of the present invention is applied to the capillary electrophoresis instrument to constitute the CE/MS, the tip of capillary can be grounded to earth, as described above, and the capillary electrophoresis can independently apply a potential thereto thus greatly simplifying its entire construction and its operation and drastically improving its operational safety.
In the conventional ionization method, such as electrospray and ion spray methods, the ionization is highly influenced by contamination around the capillary and the sampling orifice. In the sonic spray method of the present invention for producing the ions from the sample solution by the sprayed gas, on the contrary, the ionization is not influenced by contamination around the capillary and the sampling orifice.
In the conventional ionization the ion intensity to be detected is highly influenced by contamination around the sampling orifice and at the capillary. In the sonic spray method of the present invention, on the contrary, the ion intensity to be detected is influenced neither by contamination around the capillary nor by contamination around the sampling orifice so that the sample can be detected with high sensitivity and with an excellent reproducibility. In short, the capillary tip and the ion source body are arranged in optimum positions so that the ions can be produced and detected from the sample solution with an excellent reproducibility and in a high efficiency.
| |
Unidirectional glass fiber reinforced polymer (GFRP) is tested at four initial strain rates (25, 50, 100 and 200 s-1) and six temperatures ( 25, 0, 25, 50, 75 and 100°C) on a servo-hydraulic high-rate testing system to investigate any possible effects on their mechanical properties and failure patterns. Meanwhile, for the sake of illuminating strain rate and temperature effect mechanisms, glass yarn samples were complementally tested at four different strain rates (40, 80, 120 and 160 s-1) and varying temperatures (25, 50, 75 and 100°C) utilizing an Instron drop-weight impact system. In addition, quasi-static properties of GFRP and glass yarn are supplemented as references. The stress-strain responses at varying strain rates and elevated temperatures are discussed. A Weibull statistics model is used to quantify the degree of variability in tensile strength and to obtainWeibull parameters for engineering applications. | https://asu.pure.elsevier.com/en/publications/mechanical-characterization-of-the-tensile-properties-of-glass-fi |
A handsome, migratory plover breeding across the southern tip of South America and moving mainly north to winter in coastal habitats and estuaries in central Chile, Uruguay and southern Brazil, but also winters coastally at Tierra del Fuego; resident on the Falkland Islands. During the breeding season can be found relatively far inland, nesting in flooded grasslands and freshwater wetlands. Note stocky build and pot-bellied appearance, and usually double breast band (some variants have broken upper band). Similar to the Puna Plover of high Andean wetlands, a species with which its range does not typically overlap. Also see Killdeer. | https://neotropical.birds.cornell.edu/Species-Account/nb/species/twbplo1/overview |
GEORGIANS ACCUSED of a crime are presumed innocent until proven guilty. That’s how the justice system is supposed to work.
But the same due process rules don’t apply to a person’s private property.
If arresting officers suspect that an arrested person’s car, house, boat or cash was involved in a crime, they can legally seize it. Then it’s up to the owner, who remains innocent in the eyes of the law, to prove that authorities were wrong if that person wants those items returned.
No one wants criminals to profit from breaking the law. Their ill-gotten gains should be taken away.
Unfortunately, the law as written is prone to abuse. There have been occasions where innocent people have suffered, including those who’ve had to pay lawyers and fight to get their property returned.
Georgia law enforcement agencies also do a spotty job of reporting what they seize, which is required under current law. Such transparency is vital. It helps prevent agencies from being overaggressive, as there’s a built-in incentive to seize things of value, like cars, boats and cash — agencies can keep what they take.
Unfortunately, the public can be kept in the dark about such takings.
Last year, a software company employee named Josiah Neff who lives in Atlanta filed suit against authorities in Atlanta and Fulton County for failing to report seizures. Mr. Neff wasn’t a suspected lawbreaker. Instead, he’s an active member of the Libertarian Party, which has made civil asset forfeiture reform a national issue.
It took the judge 30 minutes to rule in favor of Mr. Neff. But not much has changed since then.
According to the Georgia Public Policy Foundation, a conservative think-tank in Atlanta, just 17 agencies across the state have posted reports on the centralized Web site where the law requires them to disclose seizures and their dispositions.
(The site is managed by the Carl Vinson School of Government at the University of Georgia. As of Monday, the City of Savannah hadn’t filed a report; the same goes for Chatham, Effingham and Bryan counties.)
“The lack of transparency makes it difficult for the average citizen to keep track of the millions of dollars a year that Georgia law enforcement agencies get to keep from asset forfeitures,” said Benita Dodd, the foundation’s vice president. She’s absolutely right. Again, criminals must not profit. But agencies that enforce the law must follow it, too.
The foundation believes Georgia law should be changed so that no one loses their private property until after conviction. It also wants proceeds from criminal asset forfeiture to go into the state’s general fund, as opposed to the budgets of local police, sheriffs or prosectors.
These would be major changes. But if Georgia lawmakers truly believe in private property rights and that people are innocent until proven guilty, they should offer up a reform bill and begin the debate. | http://savannahnow.com/editorial-opinion-latest-news/2012-01-16/editorial-property-rights-forfeiture-fumbles?quicktabs_3=1 |
Think of an exam as a performance and exam prep as rehearsal or a scrimmage—authentic practice.
Come up with a game plan:
- Develop a realistic study schedule based upon clear and specific goals for each session. Write down where you’ll study, at what time, and exactly what you intend to do with that time. Note: don’t plan to cram—studies show that cramming leads to higher stress and lower scores. Think in terms of a five-day plan for each course.
- Determine available study time, blocks of time for specific tasks, and study with a sense of urgency. Schedule sleep, meals, and (some) down time. Sleep deprivation reduces efficiency.
- Organize your study area and materials, and make necessary plans (e.g., with study group members).
Think like a professor:
- Grasp the big picture of the courses and your professor's objectives.
- Identify the underlying of logic of the course design by focusing on main principles, themes, and concepts first, then look for evidence (details, examples) supporting and explaining them.
- Pay particular attention to concepts professors focused upon in class or in homework, quizzes, problem sets, and other assignments.
Predict exam questions from your lecture notes, problem sets, precept discussions, and readings:
- Formulate central questions that link large chunks of course material. They will usually be derived from main principles and concepts—including how various concepts relate to each other. Practice answering them.
- Identify and classify information that might show up in an identification or short- answer section. Prepare yourself to show what you know succinctly.
Consider where your weaknesses lie:
- What concepts remain unclear? Which problems do you routinely struggle to solve? Targeting your studying will help you make the most of the time you have for each course.
- Evaluate not merely whether you "know" the material, but whether you have mastered it and can apply your knowledge in ways your professor will ask of you.
Create study aids such as:
- Reading summaries that capture main points of texts and relate them to course themes.
- Charts of theorems, mechanisms, or principles rewritten in your own words.
- A course blueprint that organizes main themes and concepts of the course.
- Problem packets in which you collate similar problems from the course and their solutions to study with.
For quantitative courses, work through problems:
- Work through previous assignments, the ends of textbook chapters, or old exams.
- Don’t think of each problem as unique; instead, look for similarities among them and common techniques for solving them.
- Don’t consult the answer key until you’ve tried to solve the problem yourself--work under test-like conditions whenever possible.
- Review our tip-sheet on preparing for problem-solving exams.
For essay exams, practice writing your response:
- Predict questions and outline your answers in preparation for the exam.
- Identify specific examples/evidence you will use to support your main points.
- If the exam is in class, time your practice runs to get a sense of the depth/quality of essays you’ll be able to produce in the time allotted.
- Evaluate your practice efforts (outlines/drafts) and consider how to refine your response.
- Practice producing your answers or outlines, not merely reviewing material.
Try to explain difficult material to someone else:
- You can do this with a study partner or in study groups. You can also work with others to generate questions.
Take practice exams:
- Take an old exam and note what types of skills and techniques are tested--practice these.
- Time yourself and use only the materials you will have at the exam; don't refer to "solutions" or a study guide--you won't have them on the actual exam...
- Review your answers and focus on filling gaps in your skills and knowledge.
Don’t be afraid to ask your instructors and AIs for help:
- If after reviewing, you still don’t understand something, take advantage of office hours or review sessions to ask questions about the material.
- Asking about the format of the exam is okay, but don’t ask what’s going to be on the test.
Sharpen your study skills for this exam and the next one with help from the McGraw Center. Our McGraw Learning Strategy Consultants can help you develop a strategic approach to learning and success in all of your courses. Sign up for a free appointment at https://mcgraw.princeton.edu/undergraduates/learning-strategy-consultations
Remember to eat well, exercise, and get enough sleep. You’ll study and perform better.
preparing_for_exams.pdf -- For additional Resources, Handouts, and Advice visit McGraw's Learning Library. | https://mcgraw.princeton.edu/preparing-for-exams |
Why use exchange-traded funds?
Exchange-traded funds (ETFs) aim to match the performance of a benchmark index. This strategy requires less frequent turnover of holdings within the fund which means fund fees tend to be significantly lower than actively managed funds. When low-cost funds post solid performance, investors keep more of what they earn.
ETFs tend to be more tax-efficient than actively managed funds. When you sell your mutual fund or ETF at a gain, you will have to pay taxes on that gain. But capital gains taxes can be incurred even if you don’t sell your shares, due to trading activity within your fund. Actively managed funds that frequently buy and sell securities are often subject to higher capital gains taxes. Because most ETFs track an index, they tend to be more tax-efficient. Exchange-traded funds allow us to construct portfolios that are globally diversified, flexible and highly liquid. | https://upstreamwm.com/FAQ/use-exchange-traded-funds/ |
Autism Spectrum Disorder
The program for Autism Spectrum Disorder (ASD) provides services to students identified as having an atypical developmental profile with a pattern of qualitative impairments in social interaction and social communication, and the presence of restricted or repetitive patterns of behavior, interests, or activities. There are a wide range of services available to students in the ASD program ranging from inclusion in general education to special classes designed to provide a structured and predictable environment. Educational services are designed to meet each student’s unique and individual needs. | https://ecsd-fl.schoolloop.com/ese/programs/asd |
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The two main goals of research and development of the automotive industry were announced / the soiled reports of the enduring heritage of the houses
The investigation of the 11th parliament of the automobile industry is on the agenda of the presidium of the Islamic Consultative Assembly, while in this period, objectives such as reforming the automotive industry system and investigating and dealing with crimes have been considered, which will soon enter the operational phase.
Khodrocar - research and investigation of the automobile industry, which has been done in each term of the Islamic Consultative Assembly as one of the monitoring tools of the representatives, this period will be implemented soon with axes such as car pricing and transfer methods of automakers. But the main point of these reports and the objections to it is that it has never been used seriously and has only become a fantasy performance and has not even been considered in the compilation of upstream documents of this industry.
However, while rejecting this statement, the members of the parliament believe that the 11th parliament, while it is only about eight months old, has decided to investigate the automobile industry, which can be considered as a criterion for the serious determination of the board in this regard. Early performance can turn this report into a practical document.
Hojjatullah Firoozi, the spokesman of the Industries and Mines Commission of the Islamic Consultative Assembly, said in an interview with a Khodrocar reporter in this regard: "One of the differences between the research and investigation of the car industry in the new parliamentary term and previous periods is when it is done." This investigation has started at the beginning of the parliament's activity and the parliament has more than three years to use the achievements of this issue.
He considers one of the reasons for not using the reports of research and investigation of the automobile industry in the previous periods of the parliament to be the inappropriate time of implementation and adds: doing late and even reading late has caused these reports to be used by previous parliaments. While the current determination of the parliament to do this issue is in a short time so that the parliament has enough time to do so.
Firoozi continues: The law provides tools for representatives to monitor industries and practices, such as questions from officials, their interpellation and questions from officials, among which research is one of the tools to the device Those who use government budgets or those that do not have sovereignty and those who carry out some acts in government should be examined, so it is a parliamentary oversight and control tool that it can use if necessary.
A spokesman for the Parliamentary Committee on Industries and Mines said: "It is even possible that in the last two years the car industry has been investigated and no objections have been found, but in the current situation, the deputies have come to the conclusion that it is necessary to do so." , This issue should be addressed.
The representative of the people of Fasa in the Islamic Consultative Assembly, stating that in the current period in the early life of the Assembly, emphasis has been placed on research and investigation in the automotive industry, states: Certainly, the output of this report will be published in less than a year. It should be used while undoubtedly the research reports of previous periods have been used and the car manufacturers are aware of the shortcomings of their system and are trying to compensate for it, and the judicial systems are also included in some of the cases and are being investigated. Have taken action.
Rejecting the ineffectiveness of the reports and the achievements of the research and investigation of previous periods of the automotive industry, he says: "Certainly, these reports are not ineffective and will have their own results."
Firoozi points out the several axes envisaged in this period of research and investigation: Obviously, the first purpose of this implementation is that the existing questions and ambiguities for the representatives on the basis of which they requested the investigation were correct or No. In the meantime, some objections may be minimal, which will be resolved with a warning, but if it is a crime, it will be sent to a judicial authority, which will investigate and investigate it.
In the end, he states that the main purpose of research and development of the automobile industry is to reform the system and, consequently, to deal with the perpetrators in case of a crime.
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What is the best replace for lottery selling cars? / Will car installment sales increase again?
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What is the best replace for lottery selling cars? / Will car installment sales increase again? | http://khodrocar.com/en/news/4276/the-two-main-goals-of-research-and-development-of-the-automotive-industry-were-announced-the-soiled-reports-of-the-enduring-heritage-of-the-houses |
Maybe you've seen Josh Liberatore pedaling his bike with a wagon behind it from, say, Lake Park Bistro, where he makes a weekly pickup of preconsumer kitchen waste, to a composting site at the Friends Community Garden, a couple of miles away.
Liberatore is a volunteer and board member for Kompost Kids, a nonprofit organization in Milwaukee — made up of adults happy to get dirty, not kids — that has put together a network of community composting sites.
Volunteers actively maintain five core sites, picking up organic waste, which does not include table scraps, from about a half-dozen restaurants and dropping it off at the nearest site. Volunteers also do monthly turnings of the compost to keep the decomposition going strong.
One core location is the just-underway demonstration site at 1980 S. Marina Drive in Bay View. Liberatore expects it will be up and running this summer, and it will be the group's largest processing site, with a variety of composting methods on display.
About 11 auxiliary sites around the city have been built by Kompost Kids but are maintained by others, typically by community garden groups. See here for a map of the various sites.
In addition to what they receive from restaurants — which pay $10 a week for pickup — sites also accept drop-offs of appropriate organic residential waste (no meat products, for example).
One reason composting is important, Liberatore said, is because organic matter "rots inefficiently in landfills and a by-product of that anaerobic decomposition is methane gas, which is up to 85 times more potent a greenhouse gas than carbon dioxide."
"In 2014, we diverted 37 metric tons just in food waste from landfills. It's a drop in the bucket — we're tiny. There's so much more out there, but we don't have the infrastructure or the volunteers," he said.
Most of their compost is used on site by the gardeners, but to handle larger amounts of organic matter they partner with The Farm's Composting in Caledonia, a licensed composting facility. The finished product is then "given as a contribution" to new community gardens.
Liberatore said the only way to get all businesses and residents composting food waste is"to have free universal pickup as part of the suite of public services." And he notes that municipal curbside composting has already happened in many cities including Seattle; Portland, Ore.; and San Francisco.
In the meantime, he said, diverting organic matter from area landfills falls to not-for-profit groups such as Kompost Kids and Growing Power, as well as for-profit composting services including Compost Crusader and Compost Express. | https://archive.jsonline.com/features/garden/kompost-kids-creates-network-of-community-composting-sites-b99485415z1-300793891.html |
School started again in late January for most young people in New South Wales, to the collective groans of students throughout the state. But for transgender (trans) and gender-diverse students, the beginning of the school year can come with additional challenges.
Misgendering. Uniforms that don’t fit identities. Mean remarks, sometimes even bullying and violence. These issues and more contribute to poor mental health outcomes in the trans and gender diverse community. (Here are two more sources: 1, 2.)
Educators working in government schools in New South Wales are obligated to ensure student welfare and prevent bullying for all their students. To make that easier for schools with trans and gender diverse students, the Department of Education and Communities issued Legal Bulletin 55, which explains the legal requirements and sets out expectations of how these students will be treated in school.
But while these are legal obligations, this approach is also the kind, ethical, and compassionate way to treat students in your care.
We know that educators want to do what’s best for their students and communities. A short version of this post could read: Be ready to listen to your students when they tell you what they need.
But to find practical suggestions, we talked to young people in our drop-in centre to see what they would have found helpful when they were at school. This article combines some of their suggestions with research from our Client Services Team.
1. Make sure your policies are inclusive
Many schools have policies that are unintentionally problematic for students who are trans or gender diverse. These can be big things – like uniforms, school camps, sports teams, and toilets, which we’ll discuss further – but also small things, like splitting up classes based on gender for activities like singing.
In addition, trans and gender diverse students and their families must also negotiate forms (for example, enrolment forms) that are not inclusive of non-binary genders. These things aren’t often done maliciously, but rather because “it’s the way we’ve always done it”.
Take the common example of splitting up a class by gender. A young person who is still figuring out their gender might find it difficult to decide if they fit in with the boys or the girls. Another young person who is transgender might experience pushback from teachers or students who don’t respect their gender. And yet another young person might not identify as male or female – so where do they go?
Often students who don’t conform to traditional gender roles may find that they are treated as if they are misbehaving or disobedient, when really they’re just trying to be true to themselves. Others may hide or feel distressed because they can’t see any way of getting the support they need.
Review your policies before a student comes out or announces they want to transition – it’s better to be prepared than to scramble to get it right. The School Audit Tool is a great starting point for this.
2. Allow students to wear uniforms that align with their genders
Uniform codes at some schools can be restrictive for students who are trans or gender diverse. This might be gender-specific uniforms, such as skirts for girls and trousers for boys, or uniform policies that don’t allow certain haircuts, hair colours or makeup choices.
One of the ways trans and gender diverse experience distress at school is through being expected to wear uniforms that align with their gender as assigned at birth. If you advocate for students to wear uniforms that affirm the gender they identify with, they will feel more comfortable, supported, and ready to learn.
For some people, hair styles and makeup can be another important way to express their gender. Consider reviewing uniform policies to loosen restrictions around this.
3. Allow students to choose whichever toilets and changing rooms are appropriate for them
Using the toilet is a daily necessity that we shouldn’t have to think much about. Get in, do your business, get out. Unfortunately, it often isn’t that simple for trans and gender diverse students. When a school does not have inclusive policies, trans and gender diverse young people may avoid using bathrooms at all. This can have serious implications for their health and wellbeing – which is [backed up by our research](.
Ideally, gender neutral bathrooms are the best way to ensure that everyone can use the bathroom safely. This should be considered when building new facilities.
Work with your students to find what solution will work for them. While many young trans and gender diverse people find using a staff or accessible toilet to be othering and dehumanising, it may be the safest option for a trans or gender diverse student until appropriate whole-of-school policies and practices reflect effective inclusion.
Some questions you can ask:
- Which bathroom are you most comfortable using?
- Would you prefer using a single-occupant bathroom?
- Can we create a separate changing area or a modified schedule for changing rooms?
- How can our school create and implement policies and practices that effectively include trans and gender diverse students?
4. Respect pronouns
Pronouns, at least in the English language, are one way that we signal a person’s gender. (For example, she/her, he/him, or they/them.) By using the correct pronouns, we are telling a person that we respect and affirm their gender.
New pronouns, as well as new names, can be easier to adjust to than you might think. Be ready to make mistakes, but also be ready to correct them without making a big deal of it. For example: “Finn was in my class last year, and he—sorry, she—was an excellent student.”
Correcting yourself is important, regardless of whether the student is there, because it sends a message that these are the correct pronouns, and they are important to get right.
Consider adding a place on attendance forms (or somewhere similar) to record students’ pronouns. Ideally, collect this information from everyone – everyone has pronouns they like to use, and it’s good practice to be sure you’re using the right ones.
5. Have a trans-inclusive curriculum
A trans-inclusive curriculum is one that tells students that trans people exist. There are many ways this can happen: including trans role models in history lessons, teaching about trans bodies in sex education classes, and teaching about the spectrum of sex (including intersex variations), sexuality, and gender in biology classes.
Trans-inclusive curricula are good for all students. As well as showing young trans and gender diverse people that they’re not alone, they also show young cisgender people (that is, folks who identify with the gender they were assigned at birth) that trans people are part of our history and our world.
To get you started, the Student Wellbeing Hub includes department-approved resources that promote diversity and inclusivity within schools.
6. Create an environment where trans and gender diverse teachers feel comfortable being out
Creating an inclusive school is not limited to students. Trans and gender diverse teachers, counsellors, administrative staff and parents are also part of the school’s community.
Coming out is a very personal experience, and one that shouldn’t be an obligation. Many trans people decide to stay in the closet to preserve their own safety. However, schools that create an inclusive working environment demonstrate to their communities that they are a space where students and teachers can feel comfortable being out.
In addition, having an environment that is safe for trans teachers will show that your school is an inclusive space to students who are figuring out their own gender!
7. Implement anti-bullying programs that are specific to gender diversity and other intersections
Anti-bullying campaigns have been a hot topic in recent times. While anti-bullying strategies are an important tool aimed at preventing harm to all young people, it’s important to make sure that anti-bullying education uses innovative strategies and goes beyond just saying “bullying is bad.”
That means talking about populations that experience more bullying and discrimination, such as LGBTIQA+ folks, people from culturally and linguistically diverse backgrounds, people with disabilities, and so forth.
Use teachable moments to discuss diversity and gender issues in general, rather than just focusing on an individual incident. There are many sites of common ground to engage people and raise their consciousness around gender in the office, staff room, and classroom. Demonstrate your support for staff that initiate and adopt inclusive behaviour.
Sometimes, there is pressure to “remain neutral” from parents and colleagues. However, it’s not possible to remain truly neutral when it comes to inclusivity. What does silence tell the community?
Useful questions to consider are:
- How can guidelines and systems already in place be used to document and address harassment based on gender diversity? In the event of harassment – how quickly and visibly will the school respond?
- How will the school respond to instances of incorrect pronoun usage (accidental or intentional), transphobia, and/or bullying (including cyberbullying)? Has the safety of the transitioning student (and siblings and peers) been adequately addressed?
- Is everyone in the school and community familiar with anti-discrimination policies and legislation?
- Will counsellors and resources be available for students and staff who may experience difficulty adjusting to their own personal issues raised by a transitioning student?
8. Consider signing up for inclusivity training
Of course, these tips are only a starting point. There are so many intricacies and strategies that we couldn’t hope to address them all in a blog post!
There is a lot of good information online, including our website’s Resource Library, the Student Wellbeing Hub, and the National LGBTI Health Alliance Knowledge Hub where you can read more about issues for trans and gender diverse people.
Your state/territory education department or the NSW Teachers Federation may be able to direct you to inclusivity training opportunities in your area. The National LGBTI Health Alliance also has a directory of LGBTIQA+ inclusivity training providers. (And while we’re biased, we are big fans of our Here and Now training!)
As we can’t hope to cover every issue that trans and gender diverse students might encounter at school in a single blog post, the links in this article provide more information, and we hope you find them (and this post) helpful.
Thanks again to the awesome humans in Drop-in who helped with this post! | https://www.twenty10.org.au/trans-students/ |
Today our own Sue Thompson and Janet Maclaren joined us to share some very special presentations.
Sue participated in a walk this past summer from New York to Toronto in support of Parkinson's Disease awareness and research. Sue herself has early onset Parkinson's. She shared her experiences on that walk and the amazing transformations it has brought to her life. She challenged us to learn the real face of Parkinson's and see the strength and ability that each of us has in different ways.
Janet Maclaren has been working with the L'Arche Community in Canada for the past 5 years. She shared the joy in this community and the amazing things that happen because of it. L'Arche brings together people with intellectual disabilities with people who don't so that they can live full lives together, and grow and learn from each other. They have over 150 communities worldwide. LPCC will be supporting L'Arche through our second collection program through February.
Rev. John also had some strong words for us today. Connecting the two guest speakers, John challenged us to consider what we see in our lives, in other people, in situations, and look deeper. We know that we're all human on the inside, that we all seek relationships and a sense of belonging. But we still need reminding to look for that human bit inside everyone. So while we may see what's on the outside, we need to open our eyes and look a little deeper into everyone. | https://www.lawrenceparkchurch.ca/podcasts/the-rooster-crows-lpcc-podcast/2017-02-05-open-your-eyes |
Survey and excavations at Dabli vas Chugta, Hanumangarh, Rajasthan
The 2011 archaeological field research was comprised of survey and excavations at the site of Dabli vas Chugta, Hanumangarh, Rajasthan. This work included geomorphological survey of selected areas in Rajasthan.
The plains of northern Rajasthan are relatively flat and large areas have low undulations that are often barely perceptible on the ground. There are also large areas that are dominated by either solitary dunes or dunes that are a part of chains. The other major feature of northern Rajasthan is the broad trace of a palaeochannel that is readily visible on satellite imagery. The landscape to the north and south of this channel is clearly marked by the presence of loose wind blown sands, whereas the soils in the channel belt itself are today being used extensively for agriculture and show signs of being considerably more developed.
In order to gain a greater understanding of the surface and immediately subsurface geomorphology, a preliminary analysis of the environmental and landscape context of a range of archaeological sites in District Hanumangarh was carried out during the season. This saw a small team of researchers make assessments of the environmental and landscape context at Dabli vas Chugta and several other sites. This site margin survey work took the form of judgmentally placed test pits and hand auger profiles, as well as opportunistic findings of exposed and available sections, brick quarry pits, wells and water boreholes. At no point did this investigation intrude on land protected by the ASI. The primary objective of this work was to investigate the local soil and site-formation processes at each of these sites. At each profile loci, the stratigraphy was recorded and photographed, located and leveled in using a Leica GPS1200 differential GPS system, and old land surfaces sampled as appropriate.
Knowledge of the archaeology of northern Rajasthan is dominated by the excavations at two sites, the Early Historic mound of Rang Mahal, and the Early and Mature Harappan site of Kalibangan. Kalibangan was the first Harappan site ever excavated, following its discovery by Luigi Tessitori in 1917 (Possehl 1999: 57-58). Extensive excavations at the site by the ASI revealed an extensive walled settlement with local Early and Mature Harappan occupation, and it remains the pre-eminent Harappan site in northern Rajasthan (Lal et al. 2003, forthcoming). Although several archaeological surveys have identified sites in the vicinity of Kalibangan (e.g. Stein 1942; Ghosh 1953, 1956, 1959), all of these lie in excess of 20 kms to the west, close to Suratgarh. Found by Vikas Pawar, the site of Dabli-vas Chugta had not been recorded in previous reconnaissance surveys, and the material seen on the surface of the mound during a visit in April 2010 indicated that was occupied during the Early and possibly also the Mature Harappan periods.
Topographic survey and excavations have shown that virtually nothing of the original mound is currently preserved. The depth of deposit throughout the excavated trenches was variable, ranging from 20 to 120 cm. This variation suggests that in some areas the archaeological deposits are only preserved as they were originally laid down upon an uneven ground surface. Some part of the site appear to have been some type of natural gullies that proved to be no major impediment to occupation. Only Early Harappan/Sothi-Siswal type material was recovered.
Project publications
Singh, R.N., Petrie, C.A., et al. (in press). Survey and excavations at Dabli vas Chugta, Hanumangarh District, Rajasthan, March 24 - April 21, 2011, BHU and University of Cambridge Archaeological Project, Indian Archaeology: A Review, 2011-2012.
Singh, R.N., Petrie, C.A., French, C.A., Bates, J., Pandey, A.K., Parikh, D., Lancelotti, C. and Redhouse, D.I. 2012. Survey and excavations at Dabli-vas Chugta, Hanumangarh District, Rajasthan, Puratattva 42: 133-147. | https://www.arch.cam.ac.uk/research/projects/past-projects/land-water-and-settlement/2011-season |
Topic modeling has been widely used for analyzing text document collections. Recently, there have been significant advancements in various topic modeling techniques, particularly in the form of probabilistic graphical modeling. State-of-the-art techniques such as Latent Dirichlet Allocation (LDA) have been successfully applied in visual text analytics. However, most of the widely-used methods based on probabilistic modeling have drawbacks in terms of consistency from multiple runs and empirical convergence. Furthermore, due to the complicatedness in the formulation and the algorithm, LDA cannot easily incorporate various types of user feedback. To tackle this problem, we propose a reliable and flexible visual analytics system for topic modeling called UTOPIAN (User-driven Topic modeling based on Interactive Nonnegative Matrix Factorization). Centered around its semi-supervised formulation, UTOPIAN enables users to interact with the topic modeling method and steer the result in a user-driven manner. We demonstrate the capability of UTOPIAN via several usage scenarios with real-world document corpuses such as InfoVis/VAST paper data set and product review data sets. | https://koreauniv.pure.elsevier.com/en/publications/utopian-user-driven-topic-modeling-based-on-interactive-nonnegati |
The University of Southampton has announced a partnership with IBM to offer students and staff cognitive computing education with unprecedented access to IBM's Watson technology and experts.
Watson represents a new era of computing based on its ability to interact in natural language, process vast amounts of disparate forms of big data, and learn from each interaction. The collaborations between IBM, Southampton and Imperial College London aim to help nurture the next generation of innovators needed; and are the first initiatives of this type in the UK.
Southampton will collaborate with IBM Watson on exciting ground-breaking interdisciplinary PhD research projects across a wide range of sectors from marine and maritime to computer science, computational chemistry and ground-breaking medical research. Southampton students will also engage with Watson through a new Cognitive Computing module as part of its Curriculum Innovation programme, which will initially be available to over 150 undergraduate and Master’s students across all disciplines.
“As a University which prides itself on being at the forefront of cutting edge technological and educational developments, the introduction of Watson into our curricular and extra-curricular activities is a natural step as we seek to transform the experience and resources available to our students and staff,” said Dr Russell Bentley, Assistant Pro-Vice-Chancellor (Education).
“In particular, Watson will be a tremendous asset to participants on our innovative Curriculum Innovation programme, which encourages students from across disciplines and subject to come together to develop new skills.
“The possibilities are endless thanks to IBM and Watson and we’re grateful for the opportunity to work in partnership with IBM to push back the boundaries of global education for now and for the future,” Dr Bentley concluded.
Rashik Parmar, Partnership Executive, IBM UK and Ireland said: “We are entering into the era of cognitive computing which has the potential to change the way people interact with technology. | https://www.southampton.ac.uk/news/2014/11/14-ibm-watson-supercomputer.page |
Q:
How can I parallelize a for loop in python using multiprocessing package?
Note: I don't need any communication between the processes/threads, I'm interested in completion signal only (that's the reason I posted this question as a new one since all other examples I've found communicated between each other).
How can I use multiprocessing package in Python 3 to parallelize the following piece of code (the end goal is to make it run faster):
a = 123
b = 456
for id in ids: # len(ids) = 10'000
# executes a binary with CLI flags
run_binary_with_id(id, a, b)
# i.e. runs "./hello_world_exec --id id --a a --b b" which takes about 30 seconds on average
I tried the following:
import multiprocessing as mp
def run_binary_with_id(id, a, b):
run_command('./hello_world_exec --id {} --a {} --b {}'.format(id, a, b))
if __name__ == '__main__':
ctx = mp.get_context('spawn')
q = ctx.Queue()
a = 123
b = 456
ids = range(10000)
for id in ids:
p = ctx.Process(target=run_binary_with_id, args=(id,a,b))
p.start()
p.join()
# The binary was executed len(ids) number of times, do other stuff assuming everything's completed at this point
or
for id in ids:
map.apply_async(run_binary_with_id, (id,a,b))
In a similar question the answer is the following:
def consume(iterator):
deque(iterator, max_len=0)
x=pool.imap_unordered(f,((i,j) for i in range(10000) for j in range(10000)))
consume(x)
which I don't really understand at all (why do I need this consume()).
A:
Trying to spawn 10000 processes to run in parallel is almost certainly going to overload your system and make it run slower than running the processes sequentially due to the overhead involved in the OS having to constantly perform context switching between processes when the number of processes far exceeds the number of CPUs/cores your system has.
You can instead use multiprocessing.Pool to limit the number of worker processes spawned for the task. The Pool constructor limits the number of processes to the number of cores your system has by default, but you can fine tune it if you'd like with the processes parameter. You can then use its map method to easily map a sequence of arguments to apply to a given function to run in parallel. It can only map one argument to the function, however, so you would have to use functools.partial to supply default values for the other arguments, which in your case do not change between calls:
from functools import partial
if __name__ == '__main__':
_run_binary_with_id = partial(run_binary_with_id, a=123, b=456)
with mp.Pool() as pool:
pool.map(_run_binary_with_id, range(10000))
| |
Jeremy founded Environmental Incentives to pioneer performance-driven conservation in the fields of water quality and wildlife management. Jeremy has facilitated stakeholder groups and guided policy-makers through the design and adoption of programs that underpin regulatory permits and define the performance outcomes for over $1 billion in federal, state and local taxpayer investments. He is creating performance contracting approaches that will unlock many more billions of dollars for public-private partnerships to improve the environment both in the US and abroad.
Jeremy applies the concepts of game theory and behavioral economics to the design of environmental programs and policies that break regulatory stand-offs and inspire action by creating compelling incentives that inspire behavior change. Jeremy is the chief strategist for Environmental Incentives and many of our government and NGO clients.
Jeremy aspires to influence the decisions and behavior of 1 billion people related to how their actions impact the environment. This will require Jeremy’s innovations related to tracking and reporting environmental outcomes to become standard approaches underpinning environmental policies, government procurement and corporate impact assessments. He sees community open data initiatives as another emerging opportunity to influence how people understand how their land use and consumption decisions impact the environment. He also aspires to create the performance contracting tools that will enable all taxpayers to understand the environmental return on investment from the use of public funds in the name of the environment. | https://enviroincentives.com/team/jeremy-sokulsky/ |
CROSS REFERENCE TO RELATED APPLICATIONS
FIELD OF THE DISCLOSURE
BACKGROUND OF THE DISCLOSURE
SUMMARY OF THE DISCLOSURE
DETAILED DESCRIPTION OF THE EXEMPLARY EMBODIMENTS
High Throughput System for Genotypic Selection
Example 1
Efficient Nonmeiotic Allele Introgression in Livestock
Example 2
Tissue Culture and Transfection
Example 3
Confirmation of Introgression
Example 4
Identification of Haplotype Markers Confirming Allele Introgression
Example 5
Identification of Haplotype Markers Confirming Introgression of Slick Phenotype
Example 6
Identification of Haplotype Markers for HH1 in Holstein Cattle
Detection of SNPs and Genes
This patent applications claims priority to U.S. Provisional Applications 62/212,840 filed Sep. 1, 2015 and 62/321,942 filed Apr. 13, 2016 which are both hereby incorporated by reference in their entirety.
The disclosure is directed to methods and kits for the detection of target alleles inserted in a desired haplotype.
Livestock and other animals have been domesticated by man since the beginnings of civilization. Reasons for man's domestication of animals include for food, clothing, protection, resistance to disease and companionship. Particular breeds of livestock have been developed having desirable traits, or lacking undesirable or dangerous ones. For example cattle have been bred for many reasons including meat production, quality of leather, docility and even aggressiveness (think bullfighting). Similarly, horses have been bred to have various traits including size and strength (draft horses), speed (thoroughbreds), stamina and heat tolerance (Arabians) and general disposition, speed and hardiness (quarter horses) desirable for specific uses. Similarly, all other livestock animals have been “inbred” to some extent, either to obtain a desirable trait from a parent or ancestor or to exclude undesirable. In each case, sexual reproduction of animal requires mixing of parent genes such that many traits from both parents are imparted to the offspring.
All methods of breeding animals, by definition, require sexual reproduction. In sexual reproduction, the diploid gametogenic cells of the male and a female gonads each carrying a single set of chromosomes from its mother and father (as do all other cells), undergo reduction and division in meiosis I. During meiosis I the chromosomes duplicate (4n) and crossover between homologous chromosomes may occur resulting in new sets of genetic information within each chromosome. Meiosis I is followed by two phases of cell division resulting in four haploid gametes each carrying a unique set of genetic information. Because genetic recombination results in new gene sequences or combinations of genes, diversity is increased.
However, in livestock animals, carefully bred over hundreds if not thousands of years, increased diversity is not desirable. What is desirable is that the animal exemplifies and maintains the traits for which it has been bred. For example, there are over 800 breeds of cattle worldwide. Some cattle are bred for suitability for a particular climate however, the most numerous are bred for particular agricultural purposes including milk production and/or beef production or for draft purposes. For example, Herefords are primarily bred for meat while Holsteins are primarily dairy animals and Simmental cattle are bred for both meat and dairy purposes. Further, such breeds also have predictable, non-metric traits such as temperament and reproductive capacity. It will be appreciated that most livestock animals, including horses, sheep, pigs etc. similarly express specific traits that are considered dependable and desirable and to exclude undesirable traits such as aggressiveness or susceptibility to disease that are undesirable.
In the desire to install beneficial traits in animals, livestock, has been bred over thousands of years to include particularly desirable traits in a single breed. Generally, animal breeds are a specific group of domestic animals having homogenous appearance (phenotype), homogenous behavior, and/or other characteristics that distinguish them from other animals of their species and result from selective breeding. Selective breeding requires sexually mating individuals with desired traits with other individuals to breed “true” for the desired trait and for the traits of the breed as a whole. Animal breeding to develop desirable breeds and a desirable traits in those breeds has a long established science requiring inbreeding, linebreeding, and outcrossing. However, during the many generations needed to develop desirable breeds of livestock, the actual genetic diversity of a breed has become greatly reduced even though its actual numbers may be very large. Consequently, the effective population size (Ne) has become extremely small for any particular breed. For example, Hayes et al. (U.S. Pub No. 2014/0220575, hereby incorporated in its entirety), estimate that, among cattle, the Ne of Holstein-Friesians is estimated to be between 50 and 100; Brown Swiss about 46; Holstein 49 and Danish Red 47. Among sheep, 35 for Dorset-Rarnboulliet-Finnsheep cross. Pigs have a slightly higher Ne estimated at <200 for Harmegnies; 85 for Duroc/Large white and 300 for Large white. Chicken show similarly small Ne for breeds such as Layers which are estimated to be between 91 and 123. This low genetic diversity means that the physical characteristics of each breed are well recognized and that the chance of an undesirable characteristic occurring in a widely used breed is extremely low and generally limited to the occurrence of spontaneous mutations.
Consequently, the ability to introduce new traits in various livestock breeds is limited and time-consuming. For example, introduction of a new trait into a desirable domestic breed requires crossbreeding an animal having a desired trait with a high-quality female of the desired breed, selection of phenotypically acceptable progeny of the desired breed having the desired trait it was crossbred for and backcrossing positive progeny with further males or females of the desired breed to arrive at an animal having all the characteristics of the breed but also including the desired trait while removing all other traits from the out breed parent. Consequently, introduction of a new trait into a valued breed takes many generations of breeding to provide a stably introduced trait into an animal but lacking all other qualities of the introduced species and breeding true for all other characteristics of the valued breed.
Breeding of valuable animals requires many generations of selective breeding to stably introduce a single trait and backcrossing the progeny to provide an animal which in all other characteristics are consistent with the well-recognized traits of the breed. Therefore, there is a need for easier ways to introduce desirable traits in livestock animals and to test those animals to determine whether novel traits they may express are the result of sexual reproduction or the result of the directed introduction of specific traits carried by specific genes within the genotype of desired livestock breed.
Recently, new techniques of gene modification and animal cloning has provided the ability to introduce specific genes or alleles into an animals genomes such as by gene editing, (see for example, U.S. Pub Nos 2014033807, 20140201857, 20140041066, 20130117870 and 20130090522 to Recombinetics, Inc., each of which is incorporated by reference hereby in its entirety). These techniques allow for the introduction of novel traits directly into the genome of valuable breeds of animals without the risk of adding detrimental or undesirable traits into that breed and within less than a generation of the animal.
Currently, valuable breeds of livestock are entered into a breed registry or studbook that lists each animal's pedigree and can be followed for many generations. This written registry has allowed animal breeders to identify valuable and prolific female and male stock and to identify and avoid breeding with undesirable animals. However, the presentation of animals of a known breed with new traits requires the animal breeder to identify how the new trait was introduced such as by planned crossing with a known breed or an unanticipated sexual occurrence with an unknown or undesirable animal. Thus, it would be helpful to identify techniques and/or methods which would help identify the source of new traits in a particular breed of livestock.
The present disclosure provides methods and kits to identify an animal that is the product of genetic manipulation to introduce a foreign or exogenous allele (genes) at a target locus of a livestock animal while maintaining the native genome of the host animal.
Therefore, in one exemplary embodiment, the disclosure provides a method to identify an animal that has an exogenous allele inserted at a target locus and that has genetic markers within a native haplotype containing the target locus. In various embodiments, the disclosure further comprises identifying the exogenous allele using Southern hybridization, in situ hybridization, PCR, array-based assays, high resolution melting (HRM) analysis, fragment analysis, Sanger fragment analysis, amplified fragment length polymorphism (AFLP) analysis, restriction fragment length polymorphism (RFLP) analysis, or single strand conformation polymorphism analysis (SSCP). In various exemplary embodiments, indentifying the native markers comprises using Southern hybridization, in situ hybridization, PCR, array-based assays, high resolution melting (HRM) analysis, fragment analysis, Sanger fragment analysis, amplified fragment length polymorphism (AFLP) analysis, restriction fragment length polymorphism (RFLP) analysis, or single strand conformation polymorphism analysis (SSCP). In various exemplary embodiments, the markers are within 500 bp of the target locus. In various other exemplary embodiments there are at least 5 markers. In other exemplary embodiments there are at least 4 markers, 3 markers or two markers. In other exemplary embodiments, at least two of the markers flank the target locus. In these exemplary embodiments, by detecting the presence of an exogenous allele at a target locus within a native haplotype, the presence of the exogenous allele due to breeding with another animal can be excluded while the presence of an exogenous allele at a target locus within a native haplotype is decisive in identifying an animal that resulting from genetic modification.
In yet another exemplary embodiment, the disclosure provides a kit for determining whether an animal is the product of sexual breeding or is the product of genetic modification. In this exemplary embodiment, the kit comprises two or more probes and/or primers for a known haplotype. In addition, in this exemplary embodiment, the kit also includes one or more probes or primers for an allele, located at a target locus that is foreign to the haplotype. In various exemplary embodiments, the kit also comes with instructions for use. In yet other exemplary embodiments, the kit further is contained in a container. In yet other embodiments, the kit further comes with reagents, ampules or test tubes required for determining whether the animal is a product of sexual breeding or genetic modification. In various exemplary embodiments, the kit includes a mailing label.
These and other features and advantages of the present disclosure will be set forth or will become more fully apparent in the description that follows and in the appended claims. The features and advantages may be realized and obtained by means of the instruments and combinations particularly pointed out in the appended claims. Furthermore, the features and advantages of the disclosure may be learned by the practice of the methods and techniques disclosed herein or will be apparent from the description, as set forth hereinafter.
The present disclosure provides methods and kits to identify an animal that is the product of genetic manipulation to introduce a foreign or exogenous allele at a target locus while maintaining the native genome of the host animal.
Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of ordinary skill in the art to which this disclosure belongs. All publications and patents specifically mentioned herein are incorporated by reference for all purposes including describing and disclosing the chemicals, instruments, statistical analyses and methodologies which are reported in the publications which might be used in connection with the disclosure. All references cited in this specification are to be taken as indicative of the level of skill in the art. Nothing herein is to be construed as an admission that the disclosure is not entitled to antedate such disclosure by virtue of prior invention.
It must be noted that as used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural reference unless the context clearly dictates otherwise. As well, the terms “a” (or “an”), “one or more” and “at least one” can be used interchangeably herein. It is also to be noted that the terms “comprising”, “including”, “characterized by” and “having” can be used interchangeably.
“Additive Genetic Effects” as used herein means average individual gene effects that can be transmitted from parent to progeny.
“Allele” as used herein refers to an alternate form of a gene. It also can be thought of as variations of DNA sequence. For instance if an animal has the genotype for a specific gene of Bb, then both B and b are alleles.
“DNA Marker” refers to a specific DNA variation that can be tested for association with a physical characteristic.
“Genotype” refers to the genetic makeup of an animal.
“Genotyping (DNA marker testing)” refers to the process by which an animal is tested to determine the particular alleles it is carrying for a specific genetic test.
“Simple Traits” refers to traits such as coat color and horned status and some diseases that are carried by a single gene.
“Complex Traits” refers to traits such as reproduction, growth and carcass that are controlled by numerous genes.
“Complex allele”—coding region that has more than one mutation within it. This makes it more difficult to determine the effect of a given mutation because researchers cannot be sure which mutation within the allele is causing the effect.
“Copy number variation” (CNVs) a form of structural variation—are alterations of the DNA of a genome that results in the cell having an abnormal or, for certain genes, a normal variation in the number of copies of one or more sections of the DNA. CNVs correspond to relatively large regions of the genome that have been deleted (fewer than the normal number) or duplicated (more than the normal number) on certain chromosomes. For example, the chromosome that normally has sections in order as A-B-C-D might instead have sections A-B-C-“Repetitive element” patterns of nucleic acids (DNA or RNA) that occur in multiple copies throughout the genome. Repetitive DNA was first detected because of its rapid reassociation kinetics.
“Quantitative variation” variation measured on a continuum (e.g. height in human beings) rather than in discrete units or categories. See continuous variation. The existence of a range of phenotypes for a specific character, differing by degree rather than by distinct qualitative differences.
“Homozygous” refers to having two copies of the same allele for a single gene such as BB.
“Heterozygous” refers to having different copies of alleles for a single gene such as Bb.”
“Locus” (plural “loci”) refers to the specific locations of a maker or a gene on a chromosome.
“Centimorgan (Cm)” a unit of recombinant frequency for measuring genetic linkage. It is defined as the distance between chromosome positions (also termed, loci or markers) for which the expected average number of intervening chromosomal crossovers in a single generation is 0.01. It is often used to infer distance along a chromosome. It is not a true physical distance however.
“Chromosomal crossover” (“crossing over”) is the exchange of genetic material between homologous chromosomes inherited by an individual from its mother and father. Each individual has a diploid set (two homologous chromosomes, e.g., 2n) one each inherited from its mother and father. During meiosis I the chromosomes duplicate (4n) and crossover between homologous regions of chromosomes received from the mother and father may occur resulting in new sets of genetic information within each chromosome. Meiosis I is followed by two phases of cell division resulting in four haploid gametes each carrying a unique set of genetic information. Because genetic recombination results in new gene sequences or combinations of genes, diversity is increased. Crossover usually occurs when homologous regions on homologous chromosomes break and then reconnect to the other chromosome.
“Marker Assisted Selection (MAS)” refers to the process by which DNA marker information is used to assist in making management decisions.
“Marker Panel” a combination of two or more DNA markers that are associated with a particular trait.
“Non-additive Genetic Effects” refers to effects such as dominance and epistasis. Codominance is the interaction of alleles at the same locus while epistasis is the interaction of alleles at different loci.
“Nucleotide” refers to a structural component of DNA that includes one of the four base chemicals: adenine (A), thymine (T), guanine (G), and cytosine (C).
“Phenotype” refers to the outward appearance of an animal that can be measured. Phenotypes are influenced by the genetic makeup of an animal and the environment.
“Single Nucleotide Polymorphism (SNP)” is a single nucleotide change in a DNA sequence.
“Haploid genotype” or “haplotype” refers to a combination of alleles, loci or DNA polymorphisms that are linked so as to cosegregate in a significant proportion of gametes during meiosis. The alleles of a haplotype may be in linkage disequilibrium (LD).
“Linkage disequilibrium (LD)” is the non-random association of alleles at different loci i.e. the presence of statistical associations between alleles at different loci that are different from what would be expected if alleles were independently, randomly sampled based on their individual allele frequencies. If there is no linkage disequilibrium between alleles at different loci they are said to be in linkage equilibrium.
The term “restriction fragment length polymorphism” or “RFLP” refers to any one of different DNA fragment lengths produced by restriction digestion of genomic DNA or cDNA with one or more endonuclease enzymes, wherein the fragment length vanes between individuals in a population.
“Introgression” also known as “introgressive hybridization”, is the movement of a gene or allele (gene flow) from one species into the gene pool of another by the repeated backcrossing of an interspecific hybrid with one of its parent species. Purposeful introgression is a long-term process; it may take many hybrid generations before the backcrossing occurs.
“Nonmeiotic introgression” genetic introgression via introduction of a gene or allele in a diploid (non-gemetic) cell. Non-meiotic introgression does not rely on sexual reproduction and does not require backcrossing and, significantly, is carried out in a single generation. In non-meiotic introgression an allele is introduced into a haplotype via homologous recombination. The allele may be introduced at the site of an existing allele to be edited from the genome or the allele can be introduced at any other desirable site.
“Transcription activator-like effector nucleases (TALENs)” are artificial restriction enzymes generated by fusing a TAL effector DNA-binding domain to a DNA cleavage domain.
“Indel” as used herein is shorthand for “insertion” or “deletion” referring to a modification of the DNA in an organism.
“Genetic marker” as used herein refers to a gene/allele or known DNA sequence with a known location on a chromosome. The markers may be any genetic marker e.g., one or more alleles, haplotypes, haplogroups, loci, quantitative trait loci, or DNA polymorphisms [restriction fragment length polymorphisms (RFLPs), amplified fragment length polymorphisms (AFLPs), single nuclear polymorphisms (SNPs), indels, short tandem repeats (STRs), microsatellites and minisatellites]. Conveniently, the markers are SNPs or STRs such as microsatellites, and more preferably SNPs. Preferably, the markers within each chromosome segment are in linkage disequilibrium.
As used herein the term “host animal” means an animal which has a native genetic complement of a recognized species or breed of animal.
As used herein, “native haplotype” or “native genome” means the natural DNA of a particular species or breed of animal that is chosen to be the recipient of a gene or allele that is not present in the host animal.
As used herein the term “genetic modification” refers to is the direct manipulation of an organism's genome using biotechnology.
As used herein the term “target locus” means a specific location of a known allele on a chromosome.
As used herein, the term “quantitative trait” refers to a trait that fits into discrete categories. Quantitative traits occur as a continuous range of variation such as that amount of milk a particular breed can give or the length of a tail. Generally, a larger group of genes controls quantitative traits.
As used herein, the term “qualitative trait” is used to refer to a trait that falls into different categories. These categories do not have any certain order. As a general rule, qualitative traits are monogenic, meaning the trait is influenced by a single gene. Examples of qualitative traits include blood type and flower color, for example.
As used herein, the term “quantitative trait locus (QTL)” is a section of DNA (the locus) that correlates with variation in a phenotype (the quantitative trait).
As used herein the term “cloning” means production of genetically identical organisms asexually.
“Somatic cell nuclear transfer” (“SCNT”) is one strategy for cloning a viable embryo from a body cell and an egg cell. The technique consists of taking an enucleated oocyte (egg cell) and implanting a donor nucleus from a somatic (body) cell.
“Orthologous” as used herein refers to a gene with similar function to a gene in an evolutionarily related species. The identification of orthologues is useful for gene function prediction. In the case of livestock, orthologous genes are found throughout the animal kingdom and those found in other mammals may be particularly useful for transgenic replacement. This is particularly true for animals of the same species, breed or lineages wherein species are defined two animals so closely related as to being able to produce fertile offspring via sexual reproduction; breed is defined as a specific group of domestic animals having homogenous phenotype, homogenous behavior and other characteristics that define the animal from others of the same species; and wherein lineage is defined as continuous line of descent; a series of organisms, populations, cells, or genes connected by ancestor/descendent relationships. For example domesticated cattle are of two distinct lineages both arising from ancient aurochs. One lineage descends from the domestication of aurochs in the Middle East while the second distinct lineage descends from the domestication of the aurochs on the Indian subcontinent.
“Genotyping” or “genetic testing” generally refers to detecting one or more markers of interest e.g., SNPs in a sample from an individual being tested, and analyzing the results obtained to determine the haplotype of the subject. As will be apparent from the disclosure herein, it is one exemplary embodiment to detect the one or more markers of interest using a high-throughput system comprising a solid support consisting essentially of or having nucleic acids of different sequence bound directly or indirectly thereto, wherein each nucleic acid of different sequence comprises a polymorphic genetic marker derived from an ancestor or founder that is representative of the current population and, more preferably wherein said high-throughput system comprises sufficient markers to be representative of the genome of the current population. Preferred samples for genotyping comprise nucleic acid, e.g., RNA or genomic DNA and preferably genomic DNA. A breed of livestock animal can be readily established by evaluating its genetic markers.
Livestock may be genotyped to identify various genetic markers. Genotyping is a term that refers to the process of determining differences in the genetic make-up (genotype) of an individual by determining the individual's DNA sequence using a biological assay and comparing it to another individual's sequence or to a reference sequence. A genetic marker is a known DNA sequence, with a known location on a chromosome; they are consistently passed on through breeding, so they can be traced through a pedigree or phylogeny. Genetic markers can be a sequence comprising a plurality of bases, or a single nucleotide polymorphism (SNP) at a known location. The breed of a livestock animal can be readily established by evaluating its genetic markers. Many markers are known and there are many different measurement techniques that attempt to correlate the markers to traits of interest, or to establish a genetic value of an animal for purposes of future breeding or expected value.
Genetic testing of animals can be performed using extremely small tissue samples, a hair follicle, for example, isolated from the tail of an animal to be tested can be used. Other examples of readily accessible samples include, for example, skin or a bodily fluid or an extract thereof or a fraction thereof. For example, a readily accessible bodily fluid includes, for example, whole blood, saliva, semen or urine. Exemplary whole blood fractions are selected from the group consisting of buffy-coat fraction, Fraction II+III obtainable by ethanol fractionation of Cohn (E. J. Cohn et al., J. Am. Chem. Soc., 68, 459 (1946), Fraction II obtainable by ethanol fractionation of Cohn (E. J. Cohn et al., J. Am. Chem. Soc., 68, 459 (1946), albumin fraction, an immunoglobulin-containing fraction and mixtures thereof, Preferably, a sample from an animal has been isolated or derived previously from an animal subject by, for example, surgery, or using a syringe or swab.
In another embodiment, a sample can comprise a cell or cell extract or mixture thereof derived from a tissue or organ such as described herein above. Nucleic acid preparation derived from organs, tissues or cells are also particularly useful.
The sample can be prepared on a solid matrix for histological analyses, or alternatively, in a suitable solution such as, for example, an extraction buffer or suspension buffer, and the present disclosure clearly extends to the testing of biological solutions thus prepared. However, in one exemplary embodiment, the high-throughput system of the present disclosure is employed using samples in solution.
In other exemplary embodiments according to the disclosure, an animal thought to have been produced by genetic manipulation can be tested to determine whether a trait exhibited by that animal is due to sexual breeding or whether the trait is present due to genetic manipulation and the animal subsequently cloned, such as by SCNT
Accordingly, the skilled artisan can design probes and/or primers to determine the origin of a phenotypic or genotypic trait. The skilled artisan is aware that a suitable probe or primer i.e., one capable of specifically detecting a marker or foreign allele at a target locus, will specifically hybridize to a region of the genome in genomic DNA from the individual being tested that comprises the marker or allele. As used herein “selectively hybridizes” means that the polynucleotide used as a probe is used under conditions where a target polynucleotide is found to hybridize to the probe at a level significantly above background. The background hybridization may occur because of other polynucleotides present, for example, in genomic DNA being screened. In this event, background implies a level of signal generated by interaction between the probe and non-specific DNA which is less than 10 fold, preferably less than 100 fold as intense as the specific interaction observed with the target DNA. The intensity of interaction are measured, for example, by radiolabelling the probe, e.g. with 32P.
As will be known to the skilled artisan a probe or primer comprises nucleic acid and may consist of synthetic oligonucleotides generally up to about 100-300 nucleotides in length and in some embodiments of about 50-100 nucleotides in length or from about 8-100 or 8-50 nucleotides in length. For example, locked nucleic acid (LNA) or protein-nucleic acid (PNA) probes or molecular beacons for the detection of one or more SNPs are generally at least about 8 to 12 nucleotides in length. Longer nucleic acid fragments up to several kilobases in length can also be used, e.g., derived from genomic DNA that has been sheared or digested with one or more restriction endonucleases. Alternatively, probes/primers can comprise RNA. However, artisans will immediately appreciate that all ranges and values between the explicitly stated bounds are contemplated, with any of the following being available as an upper or lower limit: 10, 50, 100, 120, 130, 150, 200, 250, 300, 350, 400, 450 for example up to at least 1000 nucleotides.
Exemplary probes or primers for use in the present disclosure will be compatible with the high-throughput system described herein. Exemplary probes and primers will comprise locked nucleic acid (LNA) or protein-nucleic acid (PNA) probes or molecular beacons, preferably bound to a solid phase. For example, LNA or PNA probes bound to a solid support are used, wherein the probes each comprise an SNP and sufficient probes are bound to the solid support to span the genome of the species to which an individual being tested belongs.
The number of probes or primers will vary depending upon the number of loci or QTLs being screened and, in the case of genome-wide screens, the size of the genome being screened. The determination of such parameters is readily determined by a skilled artisan without undue experimentation.
Specificity of probes or primers can also depend upon the format of hybridization or amplification reaction employed for genotyping.
The sequence(s) of any particular probe(s) or primer(s) used in the method of the present disclosure will depend upon the locus or QTL or combination thereof being screened. In this respect, the present disclosure can be generally applied to the genotyping of any locus or QTL or to the simultaneous or sequential genotyping of any number of QTLs or loci including genome-wide genotyping. This generality is not to be taken away or read down to a specific locus or QTL or combination thereof. The determination of probe/primer sequences is readily determined by a skilled artisan without undue experimentation
Standard methods are employed for designing probes and/or primers e.g., as described by Dveksler (Eds) (In: PCR Primer: A Laboratory Manual, Cold Spring Harbour Laboratories, N Y, 1995). Software packages are also publicly available for designing optimal probes and/or primers for a variety of assays, e.g., Primer 3 available from the Center for Genome Research, Cambridge, Mass., USA. Probes and/or primers are preferably assessed to determine those that do not form hairpins, self-prime, or form primer dimers (e.g. with another probe or primer used in a detection assay). Furthermore, a probe or primer (or the sequence thereof) is preferably assessed to determine the temperature at which it denatures from a target nucleic acid (i.e. the melting temperature of the probe or primer, or Tm). Methods of determining Tm are known in the art and described, for example, in Santa Lucia, Proc. Natl. Acad. Sci. USA, 95: 1460-1465, 1995 or Bresslauer et al., Proc. Natl. Acad. Sci. USA, 83: 3746-3750, 1986.
For LNA or PNA probes or molecular beacons, in some exemplary embodiments the probe or molecular beacon is at least about 8 to 12 nucleotides in length and more preferably, for the SNP to be positioned at approximately the center of the probe, thereby facilitating selective hybridization and accurate detection.
For detecting one or more SNPs using an allele-specific PCR assay or a ligase chain reaction assay, the probe/primer is generally designed such that the 3′ terminal nucleotide hybridizes to the site of the SNP. The 3′ terminal nucleotide may be complementary to any of the nucleotides known to be present at the site of the SNP. When complementary nucleotides occur in both the probe/primer and at the site of the polymorphism, the 3′ end of the probe or primer hybridizes completely to the marker of interest and facilitates, for example, PCR amplification or ligation to another nucleic acid. Accordingly, a probe or primer that completely hybridizes to the target nucleic acid produces a positive result in an assay.
For primer extension reactions, the probe/primer is generally designed such that it specifically hybridizes to a region adjacent to a specific nucleotide of interest, e.g., an SNP. While the specific hybridization of a probe or primer may be estimated by determining the degree of homology of the probe or primer to any nucleic acid using software, such as, for example, BLAST, the specificity of a probe or primer is generally determined empirically using methods known in the art.
Methods of producing/synthesizing probes and/or primers useful in the present disclosure are known in the art. For example, oligonucleotide synthesis is described, in Gait (Ed) (In: Oligonucleotide Synthesis: A Practical Approach, IRL Press, Oxford, 1984); LNA synthesis is described, for example, in Nielsen et al, J. Chem. Soc. Perkin Trans., 1: 3423, 1997; Singh and Wengel, Chem. Commun. 1247, 1998; and PNA synthesis is described, for example, in Egholm et al., Am. Chem. Soc., 114: 1895, 1992; Egholm et al., Nature, 365: 566, 1993; and Orum et al., Nucl. Acids Res., 21: 5332, 1993.
Numerous methods are known in the art for detecting the occurrence of a particular marker in a sample.
In one exemplary embodiment, a marker is detected using a probe or primer that selectively hybridizes to said marker in a sample from an individual under moderate stringency, and preferably, high stringency conditions. If the probe or primer is detectably labelled with a suitable reporter molecule, e.g., a chemiluminescent label, fluorescent label, radiolabel, enzyme, hapten, or unique oligonucleotide sequence etc., then the hybridization may be detected directly by determining binding of reporter molecule. Alternatively, hybridized probe or primer may be detected by performing an amplification reaction such as polymerase chain reaction (PCR) or similar format, and detecting the amplified nucleic acid. Preferably, the probe or primer is bound to solid support e.g., in the high-throughput system of the present disclosure.
For the purposes of defining the level of stringency to be used in the hybridization, a low stringency is defined herein as hybridization and/or a wash step(s) carried out in 2-6×SSC buffer, 0.1% (w/v) SDS at 28° C., or equivalent conditions. A moderate stringency is defined herein as hybridization and/or a wash step(s) carried out in 0.2-2×SSC buffer, 0.1% (w/v) SDS at a temperature in the range 45° C. to 65° C., or equivalent conditions. A high stringency is defined herein as hybridization and/or a wash step(s) carried out in 0.1×SSC buffer, 0.1% (w/v) SDS, or lower salt concentration, and at a temperature of at least 65° C., or equivalent conditions. Reference herein to a particular level of stringency encompasses equivalent conditions using wash/hybridization solutions other than SSC known to those skilled in the art.
Generally, the stringency is increased by reducing the concentration of SSC buffer, and/or increasing the concentration of SDS and/or increasing the temperature of the hybridization and/or wash. Those skilled in the art will be aware that the conditions for hybridization and/or wash may vary depending upon the nature of the hybridization matrix used to support the sample DNA, or the type of hybridization probe used.
Progressively higher stringency conditions can also be employed wherein the stringency is increased stepwise from lower to higher stringency conditions. Exemplary progressive stringency conditions are as follows: 2×SSC/0.1% SDS at about room temperature (hybridization conditions); 0.2×SSC/0.1% SDS at about room temperature (low stringency conditions); 0.2×SSC/0.1% SDS at about 42° C. (moderate stringency conditions); and 0.1×SSC at about 68° C. (high stringency conditions). Washing can be carried out using only one of these conditions, e.g., high stringency conditions, or each of the conditions can be used, e.g., for 10-15 minutes each, in the order listed above, repeating any or all of the steps listed. However, as mentioned above, optimal conditions will vary, depending on the particular hybridization reaction involved, and can be determined empirically.
For example, the modification of a sequence of a region (haplotype) of the genome or an expression product thereof, such as, for example, an insertion (e.g., introduction of a foreign allele at a target locus), a deletion, a transversion or a transition, is detected using a method, such as, polymerase chain reaction (PCR), strand displacement amplification, ligase chain reaction, cycling probe technology or a DNA microarray chip amongst others.
Methods of PCR are known in the art and described, for example, in Dieffenbach (ed.) and Dveksler (ed) (In: PCR Primer: A Laboratory Manual, Cold Spring Harbour Laboratories, N Y, 1995). Generally, for PCR two non-complementary nucleic acid primer molecules comprising at least about 15 nucleotides, more preferably at least 20 nucleotides in length are hybridized to different strands of a nucleic acid template molecule, and specific nucleic acid molecule copies of the template are amplified enzymatically. PCR products may be detected using electrophoresis and detection with a detectable marker that binds nucleic acids. Alternatively, one or more of the oligonucleotides is/are labeled with a detectable marker (e.g. a fluorophore) and the amplification product detected using, for example, a lightcycler (Perkin Elmer, Wellesley, Mass., USA). Clearly, the present disclosure also encompasses quantitative forms of PCR, such as, for example, Taqman assays.
Strand displacement amplification (SDA) utilizes oligonucleotides, a DNA polymerase and a restriction endonuclease to amplify a target sequence. The oligonucleotides are hybridized to a target nucleic acid and the polymerase used to produce a copy of this region. The duplexes of copied nucleic acid and target nucleic acid are then nicked with an endonuclease that specifically recognizes a sequence at the beginning of the copied nucleic acid. The DNA polymerase recognizes the nicked DNA and produces another copy of the target region at the same time displacing the previously generated nucleic acid. The advantage of SDA is that it occurs in an isothermal format, thereby facilitating high-throughput automated analysis.
Ligase chain reaction (described, for example, in EP 320,308 and U.S. Pat. No. 4,883,750) uses at least two oligonucleotides that bind to a target nucleic acid in such a way that they are adjacent. A ligase enzyme is then used to link the oligonucleotides. Using thermocycling the ligated oligonucleotides then become a target for further oligonucleotides. The ligated fragments are then detected, for example, using electrophoresis, or MALDI-TOF. Alternatively, or in addition, one or more of the probes is labeled with a detectable marker, thereby facilitating rapid detection.
Cycling Probe Technology uses chimeric synthetic probe that comprises DNA-RNA-DNA that is capable of hybridizing to a target sequence. Upon hybridization to a target sequence the RNA-DNA duplex formed is a target for RNase H thereby cleaving the probe. The cleaved probe is then detected using, for example, electrophoresis or MALDI-TOF.
Additional methods for detecting SNPs are known in the art, and reviewed, for example, in Landegren et al, Genome Research 8: 769-776, 1998) (hereby incorporated by reference in its entirety).
For example, an SNP that introduces or alters a sequence that is a recognition sequence for a restriction endonuclease is detected by digesting DNA with the endonuclease and detecting the fragment of interest using, for example, Southern blotting (described in Ausubel et al (In: Current Protocols in Molecular Biology. Wiley Interscience, ISBN 047 150338, 1987) (herein incorporated by reference in its entirety) and Sambrook et al (In: Molecular Cloning: Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratories, New York, Third Edition 2001) (herein incorporated by reference in its entirety). Alternatively, a nucleic acid amplification method described supra, is used to amplify the region surrounding the SNP. The amplification product is then incubated with the endonuclease and any resulting fragments detected, for example, by electrophoresis, MALDI-TOF or PCR.
The direct analysis of the sequence of polymorphisms of the present disclosure can be accomplished using either the dideoxy chain termination method or the Maxam-Gilbert method (see Sambrook et al., Molecular Cloning, A Laboratory Manual (2nd Ed., CSHP, New York 1989); Zyskind et al., Recombinant DNA Laboratory Manual, (Acad. Press, 1988) (incorporated herein by reference in its entirety). For example, a region of genomic DNA comprising one or more markers is amplified using an amplification reaction, e.g., PCR, and following purification of the amplification product, the amplified nucleic acid is used in a sequencing reaction to determine the sequence of one or both alleles at the site of an SNP of interest.
Alternatively, one or more SNPs is/are detected using single stranded conformational polymorphism (SSCP). SSCP relies upon the formation of secondary structures in nucleic acids and the sequence dependent nature of these secondary structures. In one form of this analysis, an amplification method, such as, for example, a method described supra, is used to amplify a nucleic acid that comprises an SNP. The amplified nucleic acids are then denatured, cooled and analyzed using, for example, non-denaturing polyacrylamide gel electrophoresis, mass spectrometry, or liquid chromatography (e.g., HPLC or dHPLC). Regions that comprise different sequences form different secondary structures, and as a consequence migrate at different rates through, for example, a gel and/or a charged field. Clearly, a detectable marker may be incorporated into a probe/primer useful in SSCP analysis to facilitate rapid marker detection.
Alternatively, any nucleotide changes may be detected using, for example, mass spectrometry or capillary electrophoresis. For example, amplified products of a region of DNA comprising an SNP from a test sample are mixed with amplified products from an individual having a known genotype at the site of the SNP. The products are denatured and allowed to re-anneal. Those samples that comprise a different nucleotide at the position of the SNP will not completely anneal to a nucleic acid molecule from the control sample thereby changing the charge and/or conformation of the nucleic acid, when compared to a completely annealed nucleic acid. Such incorrect base pairing is detectable using, for example, mass spectrometry.
Allele-specific PCR (as described, for example, In Liu et al, Genome Research, 7:389-398, 1997) (herein incorporated by reference in its entirety) is also useful for determining the presence of one or other allele of an SNP. An oligonucleotide is designed, in which the most 3′ base of the oligonucleotide hybridizes to a specific form of an SNP of interest (i.e., allele). During a PCR reaction, the 3′ end of the oligonucleotide does not hybridize to a target sequence that does not comprise the particular form of the SNP detected. Accordingly, little or no PCR product is produced, indicating that a base other than that present in the oligonucleotide is present at the site of SNP in the sample. PCR products are then detected using, for example, gel or capillary electrophoresis or mass spectrometry.
Primer extension methods (described, for example, in Dieffenbach (ed.) and Dveksler (ed) (In: PCR Primer: A Laboratory Manual, Cold Spring Harbour Laboratories, N Y, 1995)) are also useful for the detection of an SNP. An oligonucleotide is used that hybridizes to the region of a nucleic acid adjacent to the SNP. This oligonucleotide is used in a primer extension protocol with a polymerase and a free nucleotide diphosphate that corresponds to either or any of the possible bases that occur at the site of the SNP. Preferably, the nucleotide-diphosphate is labeled with a detectable marker (e.g. a fluorophore). Following primer extension, unbound labeled nucleotide diphosphates are removed, e.g. using size exclusion chromatography or electrophoresis, or hydrolyzed, using for example, alkaline phosphatase, and the incorporation of the labeled nucleotide into the oligonucleotide is detected, indicating the base that is present at the site of the SNP. Alternatively, or in addition, as exemplified herein primer extension products are detected using mass spectrometry (e.g., MALDI-TOF).
The present disclosure extends to high-throughput forms of primer extension analysis, such as, for example, minisequencing (Sy Vamen et al., Genomics 9: 341-342, 1995) (incorporated by reference in its entirety) wherein a probe or primer or multiple probes or primers is/are immobilized on a solid support (e.g. a glass slide), a sample comprising nucleic acid is brought into contact with the probe(s) or primer(s), a primer extension reaction is performed wherein each of the free nucleotide bases A, C, G, T is labeled with a different detectable marker and the presence or absence of one or more SNPs is determined by determining the detectable marker bound to each probe and/or primer.
Fluorescently labeled locked nucleic acid (LNA) molecules or fluorescently labeled protein-nucleic acid (PNA) molecules are useful for the detection of SNPs (as described in Simeonov and Nikiforov, Nucleic Acids Research, 30(17): 1-5, 2002). LNA and PNA molecules bind, with high affinity, to nucleic acid, in particular, DNA. Flurophores (in particular, rhodomine or hexachlorofluorescein) conjugated to the LNA or PNA probe fluoresce at a significantly greater level upon hybridization of the probe to target nucleic acid compared to a probe that has not hybridized to a target nucleic acid. However, the level of increase of fluorescence is not enhanced to the same level when even a single nucleotide mismatch occurs. Accordingly, the degree of fluorescence detected in a sample is indicative of the presence of a mismatch between the LNA or PNA probe and the target nucleic acid, such as, in the presence of an SNP. Preferably, fluorescently labeled LNA or PNA technology is used to detect a single base change in a nucleic acid that has been previously amplified using, for example, an amplification method described supra.
As will be apparent to the skilled artisan, LNA or PNA detection technology is amenable to a high-throughput detection of one or more markers immobilizing an LNA or PNA probe to a solid support, as described in Drum et al., Clin. Chem, 45: 1898-1905, 1999 (incorporated herein in its entirety).
Similarly, Molecular Beacons are useful for detecting SNPs directly in a sample or in an amplified product (see, for example, Mhlang and Malmberg, Methods 25: 463-471, 2001) (incorporated herein in its entirety). Molecular beacons are single stranded nucleic acid molecules with a stem-and-loop structure. The loop structure is complementary to the region surrounding the SNP of interest. The stem structure is formed by annealing two “arms” complementary to each other on either side of the probe (loop). A fluorescent moiety is bound to one arm and a quenching moiety that suppresses any detectable fluorescence when the molecular beacon is not bound to a target sequence bound to the other arm. Upon binding of the loop region to its target nucleic acid the arms are separated and fluorescence is detectable. However, even a single base mismatch significantly alters the level of fluorescence detected in a sample. Accordingly, the presence or absence of a particular base at the site of an SNP is determined by the level of fluorescence detected.
The present disclosure also encompasses other methods of detecting a genetic marker such as a unique sequence, SNP or foreign allele, such as, for example, microarrays (commercially available from, for example, Affymetrix, or described, for example, in U.S. Pat. No. 6,468,743 (incorporated herein in its entirety) or Hacia et al, Nature Genetics, 14: 441, 1996) (incorporated herein in its entirety), Taqman® Assays (commercially available from, for example, LifeTechnologies and described in Livak et al, Nature Genetics, 9:341-342, 1995) (incorporated herein by reference in its entirety), solid phase minisequencing (as described in Syvamen et al. Genomics, 13: 1008-1017, 1992) (incorporated herein by reference in its entirety), minisequencing with FRET (as described in Chen and Kwok, Nucleic Acids Res. 25: 347-353, 1997) (incorporated herein by reference in its entirety) or pyrominisequencing (as reviewed in Landegren et al., Genome Res., 8(8): 769-776, 1998) (incorporated herein by reference in its entirety).
In those cases in which the polymorphism or marker occurs in a region of nucleic acid that encodes RNA, said polymorphism or marker is detected using a method such as, for example, RT-PCR, NASBA or TMA (transcription mediated amplification).
Methods of RT-PCR are known in the art and described, for example, in Dieffenbach (ed.) and Dveksler (ed) (In: PCR Primer: A Laboratory Manual, Cold Spring Harbour Laboratories, N Y, 1995 (incorporated herein by reference in its entirety).
Methods of TMA or self-sustained sequence replication (3SR) use two or more oligonucleotides that flank a target sequence, an RNA polymerase, RNase H and a reverse transcriptase. One oligonucleotide (that also comprises a RNA polymerase binding site) hybridizes to an RNA molecule that comprises the target sequence and the reverse transcriptase produces cDNA copy of this region. RNase H is used to digest the RNA in the RNA-DNA complex, and the second oligonucleotide used to produce a copy of the cDNA. The RNA polymerase is then used to produce an RNA copy of the cDNA, and the process repeated.
NASBA systems relies on the simultaneous activity of three enzymes (a reverse transcriptase, RNase H and RNA polymerase) to selectively amplify target mRNA sequences. The mRNA template is transcribed to cDNA by reverse transcription using an oligonucleotide that hybridizes to the target sequence and comprises a RNA polymerase binding site at its 5′ end. The template RNA is digested with RNase H and double stranded DNA is synthesized. The RNA polymerase then produces multiple RNA copies of the cDNA and the process is repeated.
The hybridization to and/or amplification of a marker is detectable using, for example, electrophoresis and/or mass spectrometry. In this regard, one or more of the probes/primers and/or one or more of the nucleotides used in an amplification reactions may be labeled with a detectable marker to facilitate rapid detection of a marker, for example, a fluorescent label (e.g. Cy5 or Cy3) or a radioisotope (e.g. 32P).
Alternatively, amplification of a nucleic acid may be continuously monitored using a melting curve analysis method, such as that described in, for example, U.S. Pat. No. 6,174,670. Such methods are suited to determining the level of an alternative splice form in a biological sample.
Methods of the disclosure can identify nucleotide occurrences at SNPs using genome-wide sequencing or “microsequencing” methods. Whole-genome sequencing of individuals identifies all SNP genotypes in a single analysis. Microsequencing methods determine the identity of only a single nucleotide at a “predetermined” site. Such methods have particular utility in determining the presence and identity of polymorphisms in a target polynucleotide. Such microsequencing methods, as well as other methods for determining the nucleotide occurrence at SNP loci are discussed in Boyce-Jacino, et al., U.S. Pat. No. 6,294,336, incorporated herein by reference.
Microsequencing methods include the Genetic Bit Analysis method disclosed by Goelet, P. et al. (WO 92/15712, herein incorporated by reference). Additional, primer-guided, nucleotide incorporation procedures for assaying polymorphic sites in DNA have also been described (Komher et al, Nucl. Acids. Res. 17, 7779-7784, 1989; Sokolov, Nucl. Acids Res. 18, 3671 (1990); Syvanen et al., Genomics 8, 684-692, 1990; Kuppuswamy et al., Proc. Natl. Acad. Sci. (U.S.A.) 88, 1143-1147, 1991; Prezant et al, Hum. Mutat. 1, 159-164, 1992; Ugozzoli et al., GATA 9, 107-112, 1992; Nyren et al., Anal. Biochem. 208, 171-175, 1993; Wallace, WO 89/10414; Mundy, U.S. Pat. No. 4,656,127; Cohen et al., French Pat. No. 2,650,840; WO 91/02087). In response to the difficulties encountered in employing gel electrophoresis to analyze sequences, alternative methods for microsequencing have been developed, e.g., Macevicz, U.S. Pat. No. 5,002,867 incorporated herein by reference. Boyce-Jacino et al., U.S. Pat. No. 6,294,336 provide a solid phase sequencing method for determining the sequence of nucleic acid molecules (either DNA or RNA) by utilizing a primer that selectively binds a polynucleotide target at a site wherein the SNP is the most 3′ nucleotide selectively bound to the target. Oliphant et al., Suppl. Biotechniques, June 2002, describe the use of BeadArray™ Technology to determine the nucleotide occurrence of an SNP, Alternatively, nucleotide occurrences for SNPs can be determined using a DNA MassArray system (Sequenom, Inc., San Diego, Calif.) is used, which system combines SpectroChips™, microfluidics, nanodispensing, biochemistry, and MALDI-TOF MS (matrix-assisted laser desorption ionization time of flight mass spectrometry).
Particularly useful methods include those that are readily adaptable to a high throughput format, to a multiplex format, or to both. High-throughput systems for analyzing markers, especially SNPs, can include, for example, a platform such as the UHT SNP-IT™ platform (Orchid Biosciences, Princeton, N.J., USA) MassArray™ system (Sequenom, Inc., San Diego, Calif., USA), the integrated SNP genotyping system (Illumina, San Diego, Calif., USA), TaqMan™ (ABI, Foster City, Calif., USA), Rolling circle amplification, fluorescent polarization, amongst others described herein above. In general, SNP-IT™ is a 3-step primer extension reaction. In the first step, a target polynucleotide is isolated from a sample by hybridization to a capture primer, which provides a first level of specificity. In a second step the capture primer is extended from a terminating nucleotide trisphosphate at the target SNP site, which provides a second level of specificity. In a third step, the extended nucleotide trisphosphate can be detected using a variety of known formats, including: direct fluorescence, indirect fluorescence, an indirect colorimetric assay, mass spectrometry, fluorescence polarization, etc. Reactions can be processed in 384 well format in an automated format using an SNPstream™ instrument (Orchid BioSciences, Princeton, N.J.).
The instant disclosure also provides a high-throughput system for genotypic selection in a population having a small effective population size, in some embodiments, the system comprises a solid support consisting essentially of or having nucleic acids of different sequence bound directly or indirectly thereto, wherein each nucleic acid of different sequence comprises a polymorphic genetic marker derived from an ancestor or founder that is representative of the current population.
Exemplary high-throughput systems are hybridization mediums e.g., a microfluidic device or homogenous assay medium. Numerous microfluidic devices are known that include solid supports with microchannels (See e.g., U.S. Pat. Nos. 5,304,487, 5,110,745, 5,681,484, and 5,593,838). In one exemplary embodiment, the high throughput system comprises an SNP chip comprising 10,000-100,000 oligonucleotides each of which consists of a sequence comprising an SNP. Each of these hybridization mediums is suitable for determining the presence or absence of a marker associated with a trait.
The nucleic acids are typically oligonucleotides, attached directly or indirectly to the solid support. Accordingly, the oligonucleotides are used to determine the nucleotide occurrence of a marker associated with a trait, by virtue of the hybridization of nucleic acid from the subject being tested to an oligonucleotide of a series of oligonucleotides bound to the solid support being affected by the nucleotide occurrence of the marker in question e.g., by the presence or absence of an SNP in the subject's nucleic acid. Accordingly, oligonucleotides can be selected that bind at or near a genomic location of each marker. Such oligonucleotides can include forward and reverse oligonucleotides that can support amplification of a particular polymorphic marker present in template nucleic acid obtained from the subject being tested. Alternatively, or in addition, the oligonucleotides can include extension primer sequences that hybridize in proximity to a marker to thereby support extension to the marker for the purposes of identification. A suitable detection method will detect binding or tagging of the oligonucleotides e.g., in a genotyping method described herein.
Techniques for producing immobilized arrays of DNA molecules have been described in the art. Generally, most methods describe how to synthesize single-stranded nucleic acid molecule arrays, using for example masking techniques to build up various permutations of sequences at the various discrete positions on the solid substrate. U.S. Pat. No. 5,837,832 (hereby incorporated by reference in its entirety), the contents of which are incorporated herein by reference, describes an improved method for producing DNA arrays immobilized to silicon substrates based on very large scale integration technology. In particular, U.S. Pat. No. 5,837,832 (hereby incorporated by reference in its entirety) describes a strategy called “tiling” to synthesize specific sets of probes at spatially-defined locations on a substrate which are used to produce the immobilized DNA array. U.S. Pat. No. 5,837,832 (hereby incorporated by reference in its entirety) also provides references for earlier techniques that may also be used.
DNA can be synthesized in situ on the surface of the substrate. However, DNA may also be printed directly onto the substrate using for example robotic devices equipped with either pins or piezo electric devices. Microarrays are generally produced step-wise, by the in situ synthesis of the target directly onto the support, or alternatively, by exogenous deposition of pre-prepared targets. Photolithography, mechanical microspotting, and ink jet technology are generally employed for producing microarrays.
In photolithography, a glass wafer, modified with photolabile protecting groups, is selectively activated e.g., for DNA synthesis, by shining light through a photomask. Repeated deprotection and coupling cycles enable the preparation of high-density oligonucleotide microarrays (see for example, U.S. Pat. No. 5,744,305, issued Apr. 28, 1998) (hereby incorporated by reference in its entirety).
Microspotting encompasses deposition technologies that enable automated microarray production, by printing small quantities of pre-made target substances onto solid surfaces. Printing is accomplished by direct surface contact between the printing substrate and a delivery mechanism, such as a pin or a capillary. Robotic control systems and multiplexed print heads allow automated microarray fabrication.
Ink jet technologies utilize piezoelectric and other forms of propulsion to transfer biochemical substances from miniature nozzles to solid surfaces. Using piezoelectricity, the target sample is expelled by passing an electric current through a piezoelectric crystal which expands to expel the sample. Piezoelectric propulsion technologies include continuous and drop-on-demand devices. In addition to piezoelectric ink jets, heat may be used to form and propel drops of fluid using bubble-jet or thermal ink jet heads; however, such thermal ink jets are typically not suitable for the transfer of biological materials due to the heat which is often stressful on biological samples. Examples of the use of ink jet technology include U.S. Pat. No. 5,658,802 (hereby incorporated by reference in its entirety).
A plurality of nucleic acids is typically immobilized onto or in discrete regions of a solid substrate. The substrate is porous to allow immobilization within the substrate, or substantially non-porous to permit surface immobilization.
The solid substrate can be made of any material to which polypeptides can bind, either directly or indirectly. Examples of suitable solid substrates include flat glass, silicon wafers, mica, ceramics and organic polymers such as plastics, including polystyrene and polymethacrylate. It is also possible to use semi-permeable membranes such as nitrocellulose or nylon membranes, which are widely available. The semi-permeable membranes are mounted on a more robust solid surface such as glass. The surfaces may optionally be coated with a layer of metal, such as gold, platinum or other transition metal.
Preferably, the solid substrate is generally a material having a rigid or semi-rigid surface. In some embodiments, at least one surface of the substrate will be substantially flat, although in some embodiments it are desirable to physically separate synthesis regions for different polymers with, for example, raised regions or etched trenches. It is also an embodiment that the solid substrate is suitable for the high density application of DNA sequences in discrete areas of typically from 50 to 100 μm, giving a density of 10,000 to 40,000 cm-2.
The solid substrate is conveniently divided up into sections. This is achieved by techniques such as photoetching, or by the application of hydrophobic inks, for example Teflon-based inks (Cel-line, USA).
Discrete positions, in which each different member of the array is located may have any convenient shape, e.g., circular, rectangular, elliptical, wedge-shaped, etc.
Attachment of the nucleic acids to the substrate can be covalent or non-covalent, generally via a layer of molecules to which the nucleic acids bind. For example, the nucleic acid probes/primers can be labelled with biotin and the substrate coated with avidin and/or streptavidin. A convenient feature of using biotinylated probes/primers is that the efficiency of coupling to the solid substrate is determined easily.
A chemical interface may be provided between the solid substrate e.g., in the case of glass, and the probes/primers. Examples of suitable chemical interfaces include hexaethylene glycol, polylysine. For example, polylysine can be chemically modified using standard procedures to introduce an affinity ligand.
Other methods for attaching the probes/primers to the surface of a solid substrate include the use of coupling agents known in the art, e.g., as described in WO 98/49557 (hereby incorporated by reference in its entirety).
The high-throughput system of the present disclosure is designed to determine nucleotide occurrences of one SNP or a series of SNPs. The systems can determine nucleotide occurrences of an entire genome-wide high-density SNP map.
High-throughput systems for analyzing markers, especially SNPs, can include, for example, a platform such as the UHT SNP-IT platform (Orchid Biosciences, Princeton, N.J., USA) MassArray™ system (Sequenom, San Diego, Calif., USA), the integrated SNP genotyping system (Illumina, San Diego, Calif., USA), TaqMan™ (ABI, Foster City, Calif., USA). Exemplary nucleic acid arrays are of the type described in WO 95/11995 (hereby incorporated by reference in its entirety), WO 95/11995 (hereby incorporated by reference in its entirety) also describes sub-arrays optimized for detection of a variant form of a pre-characterized polymorphism. Such a sub-array contains probes designed to be complementary to a second reference sequence, which is an allelic variant of the first reference sequence. The inclusion of a second group (or further groups) can be particularly useful for analyzing short sub-sequences of a primary reference sequence in which multiple mutations are expected to occur within a short distance commensurate with the length of the probes (e.g., two or more mutations within 9 to 21 bases). More preferably, the high throughput system comprises a SNP microarray such as those available from Affymetrix or described, for example, in U.S. Pat. No. 6,468,743 (hereby incorporated by reference in its entirety) or Hacia et al, Nature Genetics, 14:441, 1996 (hereby incorporated by reference in its entirety).
DNA arrays are typically read at the same time by charged coupled device (CCD) camera or confocal imaging system. Alternatively, the DNA array can be placed for detection in a suitable apparatus that can move in an x-y direction, such as a plate reader. In this way, the change in characteristics for each discrete position are measured automatically by computer controlled movement of the array to place each discrete element in turn in line with the detection means.
The detection means is capable of interrogating each position in the library array optically or electrically. Examples of suitable detection means include CCD cameras or confocal imaging systems.
The system can further include a detection mechanism for detecting binding the series of oligonucleotides to the series of SNPs. Such detection mechanisms are known in the art.
The high-throughput system of the present disclosure can include a reagent handling mechanism that can be used to apply a reagent, typically a liquid, to the solid support.
The high-throughput system can also include a mechanism effective for moving a solid support and a detection mechanism.
Recently methods have been identified to make genetically modified animals using custom nucleases (TALENs) to afford efficient nonmeiotic introgression of foreign alleles into a haplotype. Such modifications can be made by identifying the specific sequence structure of a gene or allele and the sequence or sequences surrounding it on its chromosome. Due to rapid advances in molecular biology, gene sequencing and animal cloning, the ability to identify discrete genes and identify or hypothesize their function due to homology with known genes of other species has provided scientists an ability, not only to attempt to modify an animals native genetic material but to insert homologous genes (i.e., exogenous genes) from other animals, e.g., different breeds, lineages, strains or species, into an identified locus which may be the site of a native gene or allele of a host species. Further, the benefit of such insertion or introgression, is that a specific trait can be conferred on a species or breed in a single generation instead of via traditional methods of livestock breeding, cross breeding and backcrossing to confer a trait without adding of unwanted genes from the donor on the host animal. For example, U.S. Pub No. 2012/0222143, hereby incorporated in its entirety for all purposes, describes methods of using non-meiotic introgression to introduce desirable traits into livestock genome to produce a stably expressed phenotype.
Using precision gene editing, a target allele in an animal's genome and more particular a target allele within a host animals recognized haplotype can be edited with an insertion or deletion as desired. For example, efficient nonmeiotic introgression can be used to change a single base or it can be used to insert simple alleles or complex alleles, in phase, to express new traits without altering other genes, alleles or phenotypic traits that are particular to any breed of livestock.
In such examples, it may become necessary to identify whether a particular livestock animal exhibits (or lacks) some trait that is foreign to its recognized phenotype and whether the presence of that trait (or lack thereof) is the result of precise gene editing or is the result of a random mutation or sexual cross breeding with another animal that confers such trait. In such cases, the presence of a foreign or exogenous allele within a known haplotype of a domesticated animal can be identified. Those of skill in the art will appreciate that if known DNA sequences (or markers) contained within a haplotype can be identified and if foreign DNA were introduced into that haplotype at a target locus, it would be possible to identify the animal due to the presence of the inserted DNA at the site of a native allele (e.g., the target locus) within the haplotype.
Alleles on a chromosome that are in close proximity to each other exhibit a marked linkage disequilibrium such that the alleles do not segregate independently. Rather, alleles within 500 bases of each other have a high probability of segregating together even when an animal exhibiting those alleles is the product of sexual reproduction. Further, those of skill in the art recognize that the closer alleles are on a chromosome the greater the chance that they will co-segregate. Therefore, alleles and/or SNPs closer to the target locus than 500 bases can also be used as haplotype markers in some cases alleles within 200 bases, 100 bases or 50 bases will be identified. Advances in technology have provided the ability to sequence whole genomes of animals.
For example, the National Animal Genome Research Program which has a goal of coordinating the genomic sequencing of livestock including, cattle, pigs, chickens, sheep, horses and organisms used in aquaculture (See, for example, http://www.animalgenome.org/). In some cases, because livestock have been the subject of centuries of breeding and cross breeding to obtain desirable breeds, the genetic diversity of such breeds is limited. For example, Hayes et al., (U.S. Pub. No. 2014/0220575) (hereby incorporated by reference in its entirety) estimate that the effective population size (Ne) of popular livestock breeds is extremely small when compared to their large numbers and geographic distribution. For example, among cattle, the Ne of Holstein-Friesians is estimated to be between 50 and 100; Brown Swiss about 46; Holstein 49 and Danish Red 47. In sheep, the Ne for Dorset-Rarnboulliet-Finnsheep cross is 35. Pigs have a slightly high Ne estimated at <200 for Harmegnies; 85 for Duroc/Large white and 300 for Large white. Chicken show similarly small Ne for breeds such as Layers which are estimated to be between 91 and 123.
Consequently, from a breeding standpoint and from an economics standpoint, it is important to identify the source of a phenotypic trait foreign to an animal whether that arises from a natural mutation, from sexual reproduction, or whether the trait arises from a foreign allele introduced into a cloned animal. As discussed above, if a trait, such as POLLED, is introduced into a horned breed of cattle via crossing and backcrossing from, for example, a horned breed (Holstein) and a polled breed (angus) and followed by backcrossing the polled progeny with Holstein to arrive at a conventionally acceptable (e.g., subjectively phenotypic) POLLED Holstein, besides taking many generations, the genotypic results of that cross will include portions of the polled genome that are in linkage disequilibrium with the polled allele (whether expressed or not). Introducing such portions of the Angus genome may not be beneficial to the Holstein breed and may alter other traits or characteristics as well. Further, the presence of Angus alleles linked to the polled allele in the Holstein haplotype would be definitive of the introduction of the polled gene by sexual crossing. Conversely, if the polled gene was present in the haplotype due to being introduced into the haplotype by genetic manipulation, (i.e., non-meiotic introgression) the native haplotype of the host breed (Holstein) remains the same with the exception of the introduced Angus allele, nucleotide or nucleotides.
FIG. 3
In this respect, while the use of specific gene editing, such as for example, using TALENs to introduce homology directed repair (HDR) requires a knowledge of the native nucleotide sequence being replaced or interrupted, upstream or downstream sequences are irrelevant. However, as recognized by the present inventors, by identifying markers native to the host haplotype along with the correct insertion site for introduced (exogenous) DNA, it is possible to determine whether a foreign allele has been introduced into the host animal molecularly or whether a non-native allele has appeared in an animal by random mutation or by sexual reproduction. See, . This knowledge provides the owner of the animal, the breeder of the animal and the consumer of such animals the comfort of knowing that, except for the introduced, exogenous allele, the animal remains genetically the same as its host/parent.
Accordingly, in one exemplary embodiment, the disclosure comprises a method to identify whether a host animal expressing a foreign allele or phenotype the result of a spontaneous mutation, selective is breeding or is the result of genetic modification. Therefore, in this embodiment, the method includes identifying the presence of a known exogenous allele at a specific, defined locus within a haplotype. The method further includes identifying two or more markers native to the haplotype. In some exemplary embodiments, the markers flank the target locus on a chromosome. In other embodiments, the markers are on the same side of a target locus on a chromosome. Of course, those of skill in the art will appreciate that there may be more than two haplotype markers. For example, there may be three, four or five haplotype markers. The markers may flank the target locus on a chromosome or the markers may be all on the same side of the target locus on a chromosome.
Various exemplary embodiments of devices and compounds as generally described above and methods according to this disclosure, will be understood more readily by reference to the following examples, which are provided by way of illustration and are not intended to be limiting of the disclosure in any fashion.
FIG. 1A
FIG. 1B
Some beef breeds are naturally horn-free (e.g., Angus), a dominant trait referred to as POLLED (27). Two allelic variants conferring polledness have been identified on chromosome 1 (28). Meiotic introgression of the POLLED trait into horned dairy breeds can be accomplished by traditional crossbreeding, but the genetic merit of the resulting animals would rank lower owing to the admixture of unselected (inferior) alleles for net merit (i.e., milk production) into the population. The inventors undertook the nonmeiotic introgression of the Celtic POLLED allele (duplication of 212 bp that replaces 10 bp), referred to as Pc, into fibroblasts derived from horned dairy bulls. A plasmid HDR template was constructed containing a 1,594-bp fragment including the Pc allele from the Angus breed (). TALENs were designed such that they could cleave the HORNED allele but leave the Pc allele unaffected. In addition, after finding that one pair of TALENs delivered as mRNA had similar activity as plasmid DNA (Tan et al., Proc Natl Acad Sci USA. 2013 Oct. 8; 110(41):16526-31.), we chose to deliver TALENs as mRNA to eliminate the possible genomic integration of TALEN expression plasmids. Five of 226 colonies (2%) passed each PCR test shown to confirm introgression of Pc ().
Pc HDR template. A 1,784 bp fragment encompassing the Celtic POLLED allele was PCR amplified (F1: 5′-GGGCAAGTTGCTCAGCTGTTTTTG (SEQ ID 1); R1-5′-TCCGCATGGTTTAGCAGGATTCA (SEQ ID 2)) from Angus genomic DNA and TOPO cloned into the PCR 2.1 vector (Life Technologies). This plasmid was used as positive the control template for analytical primer sets and for derivation of the 1,592 bp HDR template by PCR with following primers (1594 F1: 5′-ATCGAACCTGGGTCTTCTGCATTG (SEQ ID 3); R1: 5′-TCCGCATGGTTTAGCAGGATTCA (SEQ ID 4)) and TOPO cloned as before. Each plasmid was sequence verified prior to use. Transfection grade plasmid was prepared using the Fast-Ion MIDI Plasmid Endo-Free kit (IBI Scientific) and 5 μg or 10 μg was transfected along with 2 μg HP1.3 TALEN mRNA.
The bovine POLLED allele was introgressed into a horned bull fibroblast. Cattle fibroblasts were maintained at 30° C. Each transfection was comprised of 500,000-600,000 cells resuspended in buffer “R” mixed with mRNA and oligos and electroporated using the 100 ul tips by the following parameters: input voltage; 1800V; Pulse Width; 20 ms; and pulse number; 1. Typically, 2-4 μg of TALEN expression plasmid or 1-2 μg of TALEN mRNA and 2-3 μM of oligos specific for the gene of interest were included in each transfection. Deviation from those amounts is indicated in the figure legends for both TALENs and CRISPR/Cas9 experiments. After transfection, cells were divided 60:40 into two separate wells of a 6-well dish for three days' culture at either 30° C. or 37° C. respectively. After three days, cell populations were expanded and at 37° C. until at least day 10 to assess stability of edits.
Three days post transfection, 50 to 250 cells were seeded onto 10 cm dishes and cultured until individual colonies reached circa 5 mm in diameter. At this point, 6 ml of TrypLE (Life Technologies) 1:5 (vol/vol) diluted in PBS was added and colonies were aspirated, transferred into wells of a 24-well dish well and cultured under the same conditions. Colonies reaching confluence were collected and divided for cryopreservation and genotyping.
Three of the five clones were homozygous for Pc introgression and were confirmed by sequencing, as is known in the art. Briefly, detection of Pc introgression was performed by PCR using the F1 primer (see above) and the “P” primer (5′-ACGTACTCTTCATTTCACAGCCTAC) (SEQ ID 5) using 1× MyTaq Red mix (Bioline) for 38 cycles (95° C., 25 s; 62° C., 25 s; 72° C., 60 s). A second PCR assay was performed using (F2: 5′-GTCTGGGGTGAGATAGTTTTCTTGG (SEQ ID 6); R2-5′-GGCAGAGATGTTGGTCTTGGGTGT (SEQ ID 7)). Candidates passing both tests were analyzed by PCR using the flanking F1 and R1 primers followed by TOPO cloning and sequencing.
FIG. 2
FIG. 3
Bos Taurus
Since the location of the insertion locus for the exogenous DNA is defined, markers for detecting the presence of the haplotype can be designed. As discussed above, a genetic marker may be any known DNA sequence within a chromosome segment. Because of linkage disequilibrium and non-independent assortment, alleles within a haplotype segregate together during crossing over due to various factors but including distance from the target locus. (). Identification of appropriate markers is made by identifying known sequences, preferably, within 500 bp from the target locus or more preferably within 200 base pairs of the target locus but in some embodiments may span up to 8 Mbp along a chromosome. In some embodiments, the markers flank the target. . Those of skill in the art will appreciate that two markers flanking the target locus are sufficient enough to identify the presence of the exogenous allele in the haplotype. However, it is within the scope of the disclosure to identify five or more markers unique to the native haplotype. In some embodiments a map is made of markers specific to any haplotype such that the map can be accessed at any time to identify the presence of specific markers on any chromosome of any particular locus of an animal. Once the appropriate markers are identified, methods of determining the presence of those markers can be can be used to either make probes that recognize the desired target by, for example, in situ hybridization with specific probes or make primers that will amplify desired markers, such as by PCR. Other strategies include sequencing a large segment of chromosome comprising the exogenous allele and several markers, confirming the presence of the exogenous DNA, inserted as designed, within the appropriate chromosomal segment. In this case, primers may be designed to flank the target locus in the haplotype. For example, single-molecule real-time sequencing (Pacific Biosciences) can read from 10,000 to 15,000 bp per run while chain termination sequencing (Sanger) can read from about 400 bp to 900 bp. Such distances can be suitable to confirm the correct insertion of, for example the 212 bp POLLED allele properly within the horned haplotype defined at its locus on chromosome 1 of cattle ().
“SLICK” is a mutation found in new world cattle including Senepol, Carora, Criollo Limonero and Romosinuano. The term “SLICK” was coined to refer to the cattle's short, glossy coat. This phenotype also includes differences in hair density (less), hair shaft structure type, sweat gland density, average normal body temperature, and thermoregulation efficiency. Cattle having the SLICK phenotype exhibit greatly increased abilities to thermos-regulate in tropical environments and consequently experience considerably less stress in hot environments.
The “SLICK” mutation has been mapped to chromosome 20 of the cattle genome and mutations underlying this phenotype reside with the gene for the prolactin receptor (PRLR). The gene has nine exons that can encode a polypeptide of 581 amino acids. Previous research in Senepol cattle has shown that the phenotype results from a single base deletion in exon 10 (there is no exon 1, recognized exons are 2-10) that introduces a premature stop codon (p.Leu462) and loss of the terminal 120 amino acids from the receptor. This phenotype is referred to herein as SLICK1. Senepol cattle are extremely heat tolerant and have been crossed with many other cattle breeds to provide the benefit of this dominant trait for heat tolerance.
It is now possible to introduce the one or more of the alleles that produce the SLICK phenotype into other cattle without sexual crossing (see, for example, U.S. provisional patent application 62/221,444 to Fahrenkrug et al.). It is therefore important to be able to identify that an animal exhibiting a SLICK phenotype is the product of genetic modification rather than sexual breeding. This is for several reasons. First, most cattle breeds are well characterized and are inbred having a predicted effective population size of between 50 (Holstein/Friesans) and 114 (Braunvieh). The value of such animals is that their characteristics, such as, size, meat production, milk production, number of calves a cow can produce, resistance to disease etc. are well known. Therefore the economic value of the animals is predicated on the animals' ability to match its breed's characteristics. Second, by knowing if an animal shows a trait by virtue of genetic introgression, the animal's genetic history can be followed and confirmed.
Table 1, below provides a marker analysis of SNPs around the SLICK locus. As shown, markers 1-5 are upstream of the SLICK locus on chromosome 20 and markers 6-10 are downstream of the SLICK locus. The row labeled “SNP Allele” is the locus on the chromosome where the markers (SNP) are found naturally in Senepol cattle. The row labeled “Other Allele” is the nucleotide residue of higher minor allele frequency among haired cattle and typically not found in the haplotype linked or containing SLICK. MAF is the frequency of each SNP compared to the WT within an experimental set of genotyped DNAs. The last column shows that the probability of having the SNP allele in the 10 flanking markers and not having the slick mutation is about 8×10-5. However, it should be noted that the sampling of animals for this study was heavily biased toward cattle DNA samples derived from animals influenced by a Criollo genetic base, the native sources of SLICK mutations. Therefore, the frequency of each of the markers is much more prevalent than it would be in any global/random distribution of these markers. The chance that a non-Senepol animal exhibited the deletion at Chr20-39136558 without having any of the linked markers would be 8×10-5 and this value is skewed to be more probable due to the sampling of a heavily influenced Criollo population. As noted in Table 1, the total length of the validation region is 296,033 bp, from 39,047,501 to 39,343,534.
TABLE 1
Serial Marker
1
2
3
4
5
Slick
SNP
Chr20-
Chr20-
Chr20-
Chr20-
Chr20-
Chr20-
39047501
39067164
39107872
39118063
39126055
39136558
MAF
0.425
0.419
0.424
0.422
0.322
SNP Allele
G
A
C
G
G
DEL(Slick)
Other Allele
T
G
T
A
T
C
Slick
6
7
8
9
10
total = 10
Chr20-39136558
Chr20-
Chr20-
Chr20-
Chr20-
Chr20-
Prob by
39179498
39179527
39235859
39343400
39343534
chance
0.397
0.412
0.276
0.423
0.423
8.28733E−05
DEL(Slick)
T
G
G
T
T
SLICK
Haplotype
C
C
C
A
C
C
MAF = minor allele frequency; SNP = single nucleotide polymorphism and is denoted by the coordinate position of the SNP on Chr 20 assembly of UMD 3.1 version of the bovine genome. Row designated SNP allele refers to the SNP allele represented in the SLICK Haplotype for the variant derived from Carribbean criollo cattle (i.e. the SLICK causative mutation found in Senepol cattle). Other allele represents the alternative SNP at this position as detected by the marker kit. All SNP listed in this table are bi-allelic. The probability of having the SNP allele in the 10 flanking markers and not having the SLICK mutation is about 8 × 10<sup>−5</sup>.
Table 2 identifies the major haplotypes identified by the markers of Table 1.
TABLE 2
SNP/Marker
Haplotype<sup>1</sup>
Haplotype Count
SLICK
GACGG-(Del)-TGGTT
0.541 (n = 915)
Seq ID 8
WT
TGTAT-C-CCACC
0.213 (n = 360)
Seq ID 9
8
TGTAT-C-CC<u style="single">G</u>CC
0.089 (n = 151)
Seq ID 10
5
TGTA<u style="single">G</u>-C-CCACC
0.029 (n = 49)
Seq ID 11
5/8
TGTA<u style="single">G</u>-C-CC<u style="single">G</u>CC
0.027 (n = 46)
Seq ID 12
5/6/7
TGTA<u style="single">G</u>-C-<u style="single">T</u>G<u style="single">A</u>CC
0.018 (n = 30)
Seq ID 13
8/9/10
TGTAT-C-CC<u style="single">GTT</u>
0.018 (n = 22)
Seq ID 14
Other Haplotypes (<0.01)
0.070 (n = 119)
Seven main haplotypes were identified in the SLICK validation region. As shown in Table 2, the first two haplotypes are SLICK and the WT.
Thus, the identification of reliable markers is a step toward identifying the source of a target sequence (for example, SLICK). In the case of SLICK, there have not been identified any haplotypes having the deletion of the cytosine base that do not also share all the alleles of the SLICK haplotype. Therefore, the chance that an animal from any population would have the cytosine deletion and not have the 10 other markers identified is so exceedingly low as to be impossible.
The HH1 haplotype on chromosome 5 is associated with reduced conception rate and a deficit of homozygotes in Holstein cattle. A nonsense mutation in APAF1 (APAF1 p.Q579X) was identified within HH1 using whole-genome resequencing of the predicted founder (Chief) and three of his sons. This mutation is predicted to truncate 670 amino acids (53.7) percent of the encoded APAF1 protein that contains a WD40 domain critical to protein-protein interactions. Commercial genotyping of 246,773 Holsteins revealed 5,299 APAF1 heterozygotes and zero homozygotes for the mutation. Recombinant haplotypes, defined as a portion but not all of Chief's HH1 source haplotype, were detected within the pedigree of 78,465 animals that had 54,001 SNP genotypes as of 2011 using findhap.f90 as previously described (VanRaden et al., 2011a; Sonstegard et al., 2013). All copies of the 75-marker source haplotype spanning 7.1 Mbp that contained the putative mutation appeared to trace to Chief and to no other prominent ancestors. Living animals with recombinant haplotypes that are homozygous for only a portion of the source haplotype can rule out that portion of the haplotype as not containing the lethal mutation. After processing all recombinant haplotypes, the area not ruled out was defined as the mutation-critical region, as described by Sonstegard et al. (2013).
Recombination events were detected in 78,465 animals genotyped for 43,385 SNPs from the Illumina BovineSNP50 BeadChips (Illumina, San Diego, Calif.) using edits of Wiggans et al. (2010) and standard output from findhap.f90 (VanRaden et al., 2011a) version 2, which first examined haplotypes of length 600 markers, then 200 markers, and finally output haplotypes of ≦75 markers. The program phases genotypes into haplotypes and detects recombination points between the maternal and paternal haplotype of each genotyped parent. Recombinant haplotypes contain part of the source haplotype and part of a non-source haplotype, and a descendant's phenotype status may be unknown when crossovers occur. Crossovers were detected from genotypes by directly comparing progeny to parent haplotypes within the pedigree. For each crossover, the last marker known to be from the first parental haplotype and the first marker known to be from the second parental haplotype are output. A gap may remain between those two markers if the parental haplotypes are identical in that region, some genotypes are not called, or both parents were heterozygous and alleles could not be phased leading to an unknown crossover location. Because few dams are genotyped, crossovers occurring in maternal ancestors are often undetected (Sonstegard et al., 2013).
Regions homozygous for a section of the source haplotype were removed from consideration of harboring the causative HH1 mutation. For example, if a live animal received the original HH1 haplotype from one parent and the left 20 markers of the HH1 haplotype from the other parent, the region containing those 20 markers was removed from consideration, exactly as described in Sonstegard et al. (2013) for Jersey haplotype 1.
The genomes of Chief, and two of his progeny, Ivanhoe Chief and Valiant were sequenced using sequencing by synthesis chemistry on an Illumina HiSeq 2000 platform (Illumina Inc., San Diego, Calif.). Libraries were prepared from 5 μg of genomic DNA purified from semen straws and data was generated using standard sequencing protocols provided by the manufacturer. Previous sequencing results of Mark (12×) and Chief (6×) using 454 Titanium technology were also used (Larkin et al., 2012).
The SNPs in the suspect region of BTA5 were identified using FreeB ayes (Garrison and Marth, 2012). Putative SNPs were accepted if they fit within the following criteria: 4× minimum read coverage with at least two reads aligning in each orientation (forward, reverse), and minimum allele sequencing quality >20. Upon acquiring a list of SNPs in the region, functional annotation of the variants was performed using ANNOVAR (Wang et al., 2010). The ANNOVAR program categorized SNPs by their genic or intergenic locations within the cattle genome. The program reports SNPs located within introns and exons of annotated genes, 5′ and 3′ UTR regions, and those upstream and downstream of gene positions. All coordinates pertaining to SNP and gene positions were converted from Btau4.0 to UMD3.1 genome assemblies using the program LiftOver created by the UCSC Genome Bioinformatics Group (http://genome.ucsc.edu/cgi-bin/hgLiftOver) for consistency with haplotype and genotype datasets.
Animals were selected for validation by querying a large database of 33,415 Holsteins genotyped for 54,001 SNP as constructed previously (Wiggans et al., 2010). Genotype imputation and haplotype frequencies included all 33,415 animals, but the 758 samples selected for further validation were from the Cooperative Dairy DNA Repository, which contains DNA from almost all progeny tested bulls in North America. Haplotype identification was based on the 75 SNP markers designated as the 7.1 Mbp HH1-containing interval on BTA5 (UMD3.1 coordinates 58,638,702 to 65/743,920; VanRaden et al., 2011b). An additional query was implemented to select a diverse set of non-carriers that had unique heterozygous haplotype combinations in this interval.
An SNP genotyping panel (Sequenom Inc., San Diego, Calif.) designed for the validation test (Page et al., 2004) was composed of 24 bi-directional assays for 12 putative SNPs in the refined HH1 interval region. This included all SNPs with gene boundaries found within this interval, as well as five additional SNPs observed near adjacent genes in the interval or in distal flanking regions from the APAF1 stop-gain mutation. A total of 22 of the 24 SNP assays were functional; one SNP locus was monomorphic. The call rate for all SNP loci was 100% except for UMD3_63107293 (99.3%) and UMD3_62591311 (99.9%). Results from the bi-directional assays for each SNP locus were compared for concordance and integrated into a single marker genotype score for each animal across the 11 SNP loci. Haplotypes of 11 informative SNPs were determined by PHASE v2.1.1 (Stephens et al., 2001), and a total of 24 probable haplotypes were identified (Table 3). These haplotypes are much shorter and different than those originally defined by the 75-marker window (derived from the 54,001 chip) spanning 7.1 Mbp that was used to find HH1. Two different numbering systems exist: one for the more than 2,000 different haplotypes in this 7.1 Mbp window, and a second for the 24 haplotypes in the narrow 11 SNP window for validation (Table 3).
TABLE 3
Table 3: Haplotypes of the 11 informative SNPs in Holstein Haplotype
(HH1) validation region. Allele calls were designated either 0 or 1 -
meaning that genome reference allele is designated 0 and presence of
an alternative allele is designated 1.
Haplotype<sup>1</sup>
Haplotype Count
000010-0-0011
7
000011-0-0001
5
000011-0-0111
9
000011-0-1000
64
000011-0-1001
243
000110-0-0001
60
011010-0-1001
1
011110-0-0001
4
011110-0-0011
21
011110-0-0111
179
011110-0-1000
1
011110-0-1001
25
011100-0-0111
9
100010-0-0011
7
100010-0-1001
4
100011-0-0111
22
100011-0-1001
82
100110-0-0001
69
111110-0-0001
1
111110-0-0011
34
111110-0-0110
1
111110-0-0111
117
111110-0-1001
53
111100-1-0111
498
<sup>1</sup>APAF1 stop-gain mutation is the 7th marker of this haplotype, and the only haplotype carrying the APAF1 marker. Animals homozygous 1 at this site are lost in utero. Notice there is only one haplotype in this marker kit that designates the animals carrying the lethal mutation at marker 7 (111100-1-0111). Any animals with the zero allele at this position and this haplotype would have to be the result of genome editing. HH1 information is found at this URL - http://omia.angis.org.au/OMIA000001/9913/. This mutation is found only in Holstein cattle, so it only would be edited to wild type allele in Holstein cattle. SNP positions on Chr 5 - UMD3_62591311, UMD3_63051612, UMD3_63052631, UMD3_63088973, UMD3_63091578, UMD3_63107293, UMD3_63150400, UMD3_63198664, UMD3_63209396, UMD3_63228106, UMD3_63486133.
Following validation testing using multiple datasets with varying markers and animals (Adams et al.; J. Dairy Sci, J Dairy Sci. 2016 August; 99(8):6693-701), a test for the stop-gain mutation was added to the GeneSeek Genomic Profiler (GGP) BeadChip (GeneSeek-Neogen, Lincoln, Nebr.; Neogen Corp., 2013) and subsequent chips, and genotypes were received for 246,773 Holsteins as part of routine genomic predictions.
th
th
As illustrated in Table 3, any animals with the zero allele at the 7marker, (UMD3_63150400) and that has the 111100-X-0111 haplotype would have to be the result of genome editing. Further, the possibility that the haplotype could have a random mutation at the 7marker only is 1 in 2.85 billion. Thereby obviating any possibility that the presence of a zero at the seventh marker could be a random occurrence.
While this disclosure has been described in conjunction with the various exemplary embodiments outlined above, various alternatives, modifications, variations, improvements and/or substantial equivalents, whether known or that are or may be presently unforeseen, may become apparent to those having at least ordinary skill in the art. Accordingly, the exemplary embodiments according to this disclosure, as set forth above, are intended to be illustrative not limiting. Various changes may be made without departing from the spirit and scope of the disclosure. Therefore, the disclosure is intended to embrace all known or later-developed alternatives, modifications, variations, improvements and/or substantial equivalents of these exemplary embodiments.
The following paragraphs enumerated consecutively from 1 through 43 provide for various additional aspects of the present disclosure. In one embodiment, in a first paragraph, (1), the present disclosure provides:
1. A process of making a kit for testing a livestock animal to identify an exogenous allele in a native haplotype comprising:
identifying a native haplotype potentially including the exogenous allele;
identifying the exogenous allele;
preparing two or more probes specific to the haplotype.
Bos Taurus
2. The process of paragraph 1, wherein identifying the haplotype comprises detecting the presence of markers native to the livestock in the haplotype.
3. The process of paragraphs 1 and 2, wherein identifying the exogenous allele comprises identifying the presence of a foreign allele within the haplotype.
4. The process of paragraphs 1 through 3, wherein the exogenous allele is introduced by non-meiotic introgression.
5. The process of paragraphs 1 through 4, wherein the desired haplotype is determined by two or more markers.
6. The process of paragraphs 1 through 5 wherein the two or more markers are present on either side of the exogenous allele.
7. The process of paragraphs 1 through 6, wherein the two or more markers are found within 2 Mb of the allele.
8. The process of paragraphs 1 through 7, wherein the two or more markers are found within 1 Mb of the allele.
9. The process of paragraphs 1 through 8, wherein detecting the presence of markers native to the livestock comprises a probe specific to each marker.
10. The process of paragraphs 1 through 9, wherein the markers are selected from and comprise: Chr20-39047501, Chr20-39067164, Chr20-39107872, Chr20-39118063, Chr20-39126055, Chr20-39136558, Chr20-39179498, Chr20-39179527, Chr20-39235859, Chr20-39343400, Chr20-39343534, Chr5-UMD3_62591311, Chr5-UMD3_63051612, Chr5-UMD3_63052631, Chr5-UMD3_63088973, Chr5-UMD3_63091578, Chr5-UMD3_63107293, Chr5-UMD3_63150400, Chr5-UMD3_63198664, Chr5-UMD3_63209396, Chr5-UMD3_63228106, Chr5-UMD3_63486133.
11. The process of paragraphs 1 through 10, wherein the probe is used in PCR, array-based assays, high resolution melting (HRM) analysis, fragment analysis, Sanger fragment analysis, amplified fragment length polymorphism (AFLP) analysis, restriction fragment length polymorphism (RFLP) analysis, or single strand conformation polymorphism analysis (SSCP).
12. The process of paragraphs 1 through 11, wherein the markers are sequence specific regions of the haplotype.
13. The process of paragraphs 1 through 12, wherein the exogenous allele is derived from a different lineage, breed or species from the livestock.
14. The process of paragraph 1 through 13, wherein identifying the exogenous allele comprises using a probe specific to the exogenous allele.
15. The process of paragraphs 1 through 14, wherein the probe is used in PCR, array-based assays, high resolution melting (HRM) analysis, fragment analysis, Sanger fragment analysis, amplified fragment length polymorphism (AFLP) analysis, restriction fragment length polymorphism (RFLP) analysis, or single strand conformation polymorphism analysis (SSCP).
16. The process of paragraphs 1 through 15, wherein the exogenous allele comprises at least one base foreign to the livestock's native allele.
17. A method of identifying the presence of an exogenous, target, allele in a livestock animal comprising:
i) identifying a native haplotype in the livestock animal;
ii) identifying an allele exogenous to the haplotype;
iii) determining the presence of the exogenous allele in the haplotype.
Bos Taurus
18. The method of paragraphs 1 through 17, wherein identifying the desired haplotype comprises detecting the presence of markers native to the livestock in the haplotype.
19. The method of any of paragraphs 1 through 18, wherein identifying the exogenous allele in the haplotype comprises identifying the presence of a foreign allele within the haplotype.
20. The method of any of paragraphs 1 through 19, wherein the exogenous allele is introduced by non-meiotic introgression.
21. The method of any of paragraphs 1 through 20, wherein the haplotype is identified by two or more markers.
22. The method of any of paragraphs 1 through 21, wherein the two or more markers are present on either side of the exogenous allele.
23. The method of any of paragraphs 1 through 22, wherein the two or more markers are identified using probes specific to each marker.
24. The method of any of paragraphs 1 through 23, wherein the two or more markers are found within 2 MB of the allele.
25. The method of any of paragraphs 1 through 24, wherein the two or more markers are found within 1 MB of the allele.
26. The method of any of paragraphs 1 through 25, wherein the markers are selected from and comprise: Chr20-39047501, Chr20-39067164, Chr20-39107872, Chr20-39118063, Chr20-39126055, Chr20-39136558, Chr20-39179498, Chr20-39179527, Chr20-39235859, Chr20-39343400, Chr20-39343534, Chr5-UMD3_62591311, Chr5-UMD3_63051612, Chr5-UMD3_63052631, Chr5-UMD3_63088973, Chr5-UMD3_63091578, Chr5-UMD3_63107293, Chr5-UMD3_63150400, Chr5-UMD3_63198664, Chr5-UMD3_63209396, Chr5-UMD3_63228106, Chr5-UMD3_63486133
27. The method of any of paragraphs 1 through 26, wherein detecting the presence of markers native to the livestock comprises a probe specific to each marker.
28. The method of any of paragraphs 1 through 27, wherein the probe can be used in PCR, array-based assays, high resolution melting (HRM) analysis, fragment analysis, Sanger fragment analysis, amplified fragment length polymorphism (AFLP) analysis, restriction fragment length polymorphism (RFLP) analysis, or single strand conformation polymorphism analysis (SSCP).
29. The method of any of paragraphs 1 through 28, wherein the markers are sequence specific regions of the haplotype.
30. The method of any of paragraphs 1 through 29, wherein the exogenous allele is derived from a different lineage, breed or species from the livestock.
31. The method of any of paragraphs 1 through 30, wherein identifying the exogenous allele comprises using a probe specific to the exogenous allele.
32. The method of any of paragraphs 1 through 31, wherein the probe is used in PCR, array-based assays, high resolution melting (HRM) analysis, fragment analysis, Sanger fragment analysis, amplified fragment length polymorphism (AFLP) analysis, restriction fragment length polymorphism (RFLP) analysis, or single strand conformation polymorphism analysis (SSCP).
33. The method of any of paragraphs 1 through 32, wherein the exogenous allele comprises at least one base foreign to the livestock's native haplotype.
34. A kit for determining the presence of an exogenous allele introduced into a haplotype using non-meiotic introgression comprising:
a probe specific to an allele foreign to an animal
two or more probes specific to a haplotype of the animal
Bos Taurus.
Bos Taurus.
Bos Taurus.
35. The kit of paragraph 34, further comprising instructions for use.
36. The kit of paragraphs 34 and 35, further comprising a container for holding reaction mixtures.
37. The kit of paragraphs 34 through 36, further comprising reagents.
38. The kit of paragraphs 34 through 38, wherein the probes are for use in: PCR, array-based assays, high resolution melting (HRM) analysis, fragment analysis, Sanger fragment analysis, amplified fragment length polymorphism (AFLP) analysis, restriction fragment length polymorphism (RFLP) analysis, or single strand conformation polymorphism analysis (SSCP).
39. The kit of paragraphs 34 through 38, wherein the probes are specific for markers comprising: Chr20-39047501, Chr20-39067164, Chr20-39107872, Chr20-39118063, Chr20-39126055, Chr20-39136558, Chr20-39179498, Chr20-39179527, Chr20-39235859, Chr20-39343400, Chr20-39343534, Chr5-UMD3_62591311, Chr5-UMD3_63051612, Chr5-UMD3_63052631, Chr5-UMD3_63088973, Chr5-UMD3_63091578, Chr5-UMD3_63107293, Chr5-UMD3_63150400, Chr5-UMD3_63198664, Chr5-UMD3_63209396, Chr5-UMD3_63228106, Chr5-UMD3_63486133.
40. A genetically modified animal consisting of a genome edited at about Chr5-UMD3_63150400 or about Chr20-39136558 of
41. A method of making a genetically modified animal having a slick phenotype comprising a modification at about the Chr20-39136558 locus of
42. An in vitro animal cell comprising a modification at about Chr5-UMD3_63150400 or about Chr20-39136558 of
43. Use of a method according to any of the above paragraphs for detecting the presence of a foreign allele in a desired haplotype.
All patents, publications, and journal articles set forth herein are hereby incorporated by reference herein; in case of conflict, the instant specification is controlling.
While this disclosure has been described in conjunction with the various exemplary embodiments outlined above, various alternatives, modifications, variations, improvements, and/or substantial equivalents, whether known or that are or may be presently unforeseen, may become apparent to those having at least ordinary skill in the art. Accordingly, the exemplary embodiments according to this disclosure, as set forth above, are intended to be illustrative, not limiting. Various changes may be made without departing from the spirit and scope of the disclosure. Therefore, the disclosure is intended to embrace all known or later-developed alternatives, modifications, variations, improvements, and/or substantial equivalents of these exemplary embodiments.
BRIEF DESCRIPTION OF THE DRAWINGS
Various exemplary embodiments of the compositions and methods according to the disclosure will be described in detail, with reference to the following figures wherein:
FIG. 1
, TALEN-mediated introgression of Polled. (A) Strategy for introgressing the Pc allele into Holstein (HORNED) cells. The Pc allele is a tandem repeat of 212 bp (red arrow) with a 10-bp deletion (not shown). TALENs were developed to specifically target the HORNED allele (green vertical arrow), which could be repaired by homologous recombination using the Pc HDR plasmid. Primer sets used in B are depicted. (B) Representative images of colonies with homozygous or heterozygous introgression of Pc. Three primer sets, indicated by number, were used for positive classification of candidate colonies: set 1, F1+R1; set 2, F2+R2; and set 3, F1+P (Pc-specific). Amplicons generated using positive control templates (P, plasmid template containing a sequence-verified Pc 1,748-bp insert between primers F1 and R1; H, Holstein bull genomic DNA) are shown. The identity of the PCR products was confirmed by sequencing of F1+R1 amplicons.
FIG. 2
is a schematic illustrating crossing over during meiotic recombination.
FIG. 3
, is a schematic illustrating the genetic identification of an introduced allele either by recombination, spontaneous mutation or non-meiotic introgression. | |
Gerrard White is currently seeking an Infrastructure Platform Engineer to join the Wintel Infrastructure Operations Team of one of the UK's largest insurance companies. You will assist the team to ensure systems are maintained, enhanced, while providing technical support to tech and business team and contribute to technology, infrastructure and platform projects and solve problems based on insight. Key to the role is ensuring system availability, performance, resilience and stability service levels are achieved through platform maintenance and development.
Key Responsibilities:
Manage platform developments, enhancements and changes to maximise uptime, capacity and service levels
Contribute to platform operational maintenance and on-going BAU activity
Setup, install, configure, and upgrade virtual and physical server hardware/software environments
Ensure platform availability, stability, resilience and performance to meet business needs
Collaborate with other operational teams as an SME and contribute to operational service levels
Contribute to tech projects and help develop tech solutions that deliver exceptional customer experiences
Ensure support requests are managed and resolved within agreed processes and practices
Use a variety of scripting languages and automation techniques to develop and maintain hardware/software. Ideally Powershell.
Suitable candidates will have experience of the following technologies: | https://www.gerrardwhite.com/job/infrastructure-engineer-insurance |
Singapore, 6 January 2017 – Singapore has had a challenging 2016, buffeted by events happening many miles from her shores. The trend towards deglobalisation, notably in the United States and the United Kingdom, have cast a gloomy outlook on the global economy and this poses risks for Singapore whose economy relies heavily on international trade.
2016 also marks the implementation phase of the Base Erosion and Profit Shifting (BEPS) Project – an ambitious revamp of corporate tax rules by the world’s major economies to ensure multinational corporations pay their fair share of taxes. The desire to level the tax playing field may affect countries like Singapore where relatively low taxes are a competitive advantage.
Against this backdrop and coming on the back of soon-to-be-released recommendations by the Committee on the Future Economy, Budget 2017 will certainly be a keenly awaited one, although one should not expect silver bullets for the various challenges facing Singapore.
With the above in mind, Deloitte Singapore calls upon the Government to build on the strong foundations laid in previous Budgets – helping Singapore businesses survive and thrive amidst uncertain economic conditions by reinforcing the pillars of innovation and internationalisation, whilst carefully steering Singapore through choppy BEPS waters by ensuring that our tax regime remains transparent and acceptable in the international tax arena. Deloitte’s Budget 2017 feedback is broadly organised along the following key themes that aim to navigate Singapore through the challenges in hopes of creating more opportunities for our future.
‘Innovation’ is an all-encompassing term; indeed, Minister for Finance Mr Heng Swee Keat once remarked that “There is no textbook answer to innovation”. An archetypal case of innovation would be Uber, which by combining existing technologies such as the global positioning system and online payment system was able to create new value for its customers.
“Innovation does not necessarily involve the creation of something new from scratch. Taxpayers who undertake innovative activities – which in certain instances may just be shy by a whisker from being regarded as research and development (R&D) as per the definition under the Singapore Income Tax Act – may be frustrated by the lack of broad-based support,” says Mr Low Hwee Chua, Regional Managing Partner for Tax at Deloitte Singapore and Southeast Asia.
With the popular Productivity and Innovation Credit (PIC) Scheme set to end in 2017, Deloitte Singapore is calling for more support for innovative activities to complement existing incentives for R&D. This could come in the form of enhanced tax deductions for spending incurred on “innovative activities” that lead to the creation of new products or services.
In line with the Smart Nation initiative, the Government could also consider introducing enhanced tax deductions to encourage digitisation, such as designing and implementing e-billing systems or workflow systems, so as to subsidise part of the upfront costs.
“Currently, purchases of computer hardware and software are incentivised under the PIC scheme. With the PIC scheme coming to an end, the Government may wish to consider incentivising personnel or consultants’ costs involved in the digitisation of processes – the nexus between such expenditure and improvements in productivity may be greater, as compared to mere purchases of computer equipment,” says Mr Daniel Ho, Tax Partner and Tax Leader for Public Sector at Deloitte Singapore.
Amidst keen competition from many countries for R&D dollars, Deloitte Singapore is also proposing enhancements to Singapore’s existing R&D tax regime so that both local and foreign businesses continue to anchor their R&D activities in the city-state.
“As the PIC scheme expires at the end of 2017, there is a perceived gap in broad-based R&D tax incentives, leading to a concern that this may hinder the general development of Singapore’s R&D capabilities and innovative culture. As an alternative to granting additional tax deductions on qualifying R&D expenditure, the Government could consider granting R&D tax credits. This would be calculated based on the R&D expenditure incurred and it would achieve the same objective of decoupling the R&D regime from Singapore’s tax rate to ensure that Singapore remains attractive to R&D investments,” says Mr Lee Tiong Heng, Tax Partner and Leader of R&D and Government Incentives at Deloitte Singapore and Southeast Asia.
In addition, Deloitte Singapore is calling for enhancements to existing policies to make it more attractive to invest in start-ups, which generally carry a higher level of risk. This broadly entails giving certainty to investors – that should their investments in a start-up turn a profit, their divestment gains would be exempted from taxes. It also increases the certainty for such start-ups on the use of brought forward tax losses which may otherwise be forfeited if there is a substantial change in shareholders.
In light of a weaker global economic outlook, Deloitte Singapore proposes that the Government continues with current fiscal expansionary policies albeit with some enhancements. Firstly, the existing loss carry-back relief system could be enhanced. Allowing businesses to carry-back a higher amount of losses to profitable years would help businesses obtain a correspondingly higher amount of refund for taxes paid in prior periods. This would help alleviate cash-flow issues impacting businesses amidst a downturn.
“Beyond aiding businesses during tough economic times, the Government should also encourage them to build up their capabilities so that they are better placed to seize opportunities when the economy recovers,” says Mr Low Hwee Chua, Regional Managing Partner for Tax at Deloitte Singapore and Southeast Asia.
Amongst others, the Government could allow more renovation and refurbishment expenses to rank for tax deduction so as to encourage businesses, such as those in the retail sector, to refresh their premises.
In the medium to long term, increasing automation and technological disruption, especially in the services and manufacturing industries, coupled with a high mismatch of skills (in particular IT-related skills) between job openings and job seekers, may mean that laid-off workers would be competing for fewer job openings and consequently take a longer time to find jobs.
In line with the Government’s active promotion of life-long learning amongst Singaporeans, Deloitte Singapore proposes that skills upgrading can be given a boost by granting further tax deductions to employers for absentee payroll where such expenses are not already defrayed by grants.
To encourage employers to provide more healthcare benefits for their employees and in view of the rising medical costs, Deloitte Singapore recommends increasing the cap on tax deduction for medical expenses. To support employees in managing chronic diseases, expenses incurred on preventive health screenings and the like should be fully deductible.
“Incentives should be provided to employers that hire older Singaporeans in their workplace; this may include allowing a double deduction on Medisave contribution to CPF for older workers. In addition, to encourage individuals to take responsibility for healthcare needs, the Government should consider granting personal relief for premiums paid for medical insurance,” says Ms Jill Lim, Tax Partner and Leader of Global Employer Services at Deloitte Singapore and Southeast Asia.
In line with the Government’s vision to enhance the Singapore core and develop local talent, Deloitte Singapore suggests introducing an enhanced tax deduction for costs incurred in hiring Singaporeans for key roles and possibly a relaxation of the qualifying criteria for the Not Ordinarily Resident Scheme. This is so that Singapore citizens and permanent residents with regional or global roles that require extensive travel may see a reduction in their tax burden.
“To further encourage Singapore businesses to branch out and think regionally, the government can also consider enhancements to policies such as the foreign-sourced income exemption and foreign tax credit schemes; and possibly granting a special tax deduction for interest and related funding costs incurred to support overseas investments. This could be designed to target specifically at SMEs to encourage them to grow, and may also benefit the Singapore financial industry,” says Mr Daniel Ho, Tax Partner at Deloitte Singapore.
International tax developments have a significant impact on Singapore both as a preferred hub in Asia Pacific for foreign investment, as well as for Singapore-based companies investing overseas. To keep pace with these developments, Deloitte Singapore has included in its Budget 2017 feedback, proposals for the Government to review whether Singapore’s headline corporate tax rate of 17% will remain competitive in the international arena in the medium to long term, as well as the need to articulate Singapore’s tax policy for offshore suppliers of digital services.
“The international tax agenda has in recent years been dominated by calls from developed countries to end harmful tax competition. Somewhat ironically, some of these countries have recently announced plans to reduce their tax rates to unprecedented low rates. Although nobody wants to see a race to the bottom, Singapore would undoubtedly be keeping a close eye on these developments to ensure that her tax regime remains competitive,” says Mr Low Hwee Chua, Regional Managing Partner for Tax at Deloitte Singapore and Southeast Asia.
Apart from the above recommendations, Deloitte Singapore has also provided suggestions for specific sectors such as the financial services, marine and aerospace industries; certain broad-based business tax recommendations as well as enhancements for personal tax and goods and services tax. The specific details are available in Deloitte’s Budget 2017 feedback. | https://www2.deloitte.com/sg/en/pages/about-deloitte/articles/tax-sg-budget-2017-feedback.html |
Represent the affiliate’s medical/scientific voice of expertise. Provide medical / scientific expert advice / guidance to key customers, including scientific exchange and professional relationship development with key thought leaders / external experts.
Provide medical / scientific input into Medical Affairs strategies for the affiliate medical department and commercial plans, as required, and medical / scientific support for medical department activities under the overall direction of the Affiliate Medical Director.
Provide medical affairs support to cross-functional affiliate brand teams.
Ensure that the medical affairs role is fully integrated to support the strategy and execution of affiliate business, while being functionally independent.
Responsibilities:
- Provide expert medical/scientific advice, including responding to requests for scientific/technical information; contribute to the development and medical and scientific accuracy of core dossiers generated by the medical department
- Develop medical affairs plans and allocate associated budget for the affiliate medical department and provide input to local commercial brand plans; collaborate and partner with local business partners to ensure that medical activities are aligned with local business-related strategic plans.
- Establish and maintain professional and credible relationships with key thought leaders / external experts and academic centers; this will involve in-field customer interactions and participating in scientific congresses, coordinating advisory boards, round-table meetings, discussion fora etc.
- Deliver scientific presentations and medical education programs to healthcare professionals individually or in groups (meetings, clinical sessions, etc.), where appropriate.
- Screen relevant literature and other information from relevant scientific societies meetings and conferences and (e.g. key areas of scientific/company interest, new trends in diagnosis, monitoring and treatments in the therapeutic area, etc.) and give input into strategy
- Deliver training to in field teams and functions in other departments; develop and update relevant training materials.
- Review of promotional material made by the brand manager. Ensure the medical/scientific content is correct and fully compliant with AbbVie’s internal policies and guidelines.
- As core member of the brand team, provide medical/scientific input into marketing strategy and key commercial initiatives, as required. Monitor the environment for competitive intelligence (e.g. product strategies, studies, commercial messages, positioning, etc.)
- Ensure compliance with all applicable national laws and regulations, guidelines, codes of conduct, the company's policies and procedures and accepted standards of best practice.
Profile
- Medical Degree or a master degree in a scientific discipline or higher, with experience in a similar role in the pharmaceutical industry.
- Fluently in English, Flemish and French
- Keen interest in developing and maintaining expert knowledge for assigned therapeutic area/product and in medical research in general.
- Excellent written and spoken communication and presentation skills.
- Fluency in written and oral English is highly desirable in order to facilitate communications between the affiliate medical department, Regional and Area Medical Affairs and other functional staff. | https://www.houseoftalents.be/en/science-talents/vacancies/medical-advisor |
The discovery of the green fluorescent protein, which is providing researchers with new insight into various diseases, wins 2008 Nobel chemistry prize
The 2008 Nobel Prize in chemistry has been awarded jointly to Osamu Shimomura, of Boston University, Massachusetts and Martin Chalfie, of Columbia University, New York and Roger Y. Tsien, of the University of California San Diego, in La Jolla for the discovery and development of the green fluorescent protein, GFP, found in jellyfish.
So, how can a glowing jellyfish protein be worthy of a Nobel Prize?
Aequorea victoria drifts with the currents off the west coast of North America and is remarkable in that it produces a green and eerie glow. In the 1960s, Shimomura was studying bioluminescence, the chemical reactions within living organisms that produce light. He had isolated a bioluminescent protein that gave off paradoxically blue not green light from A. victoria. His follow-on studies revealed in 1962 a second jellyfish protein that absorbs the blue light from the first and re-emits it as a green glow. The protein was later to become known as green fluorescent protein (GFP).
In 1988, Chalfie heard about GFP for the first time and a light went on. He reasoned that this unassisted fluorescence might be used as a beacon in cells to flag different processes. He engineered the gene for GFP into the DNA of the molecular biologist's favourite worm Caenorhabditis elegans. Its cells glowed green without the need to add any biochemical agents and without harming the worm. Subsequent work showed that it was possible to fuse the gene for GFP to genes for other proteins, opening-up a method for tracking the specific proteins in living organisms.
For his share of the Nobel Prize, Tsien added to the general understanding of how GFP, and relatives from other luminescent organisms and genetically engineered varieties, actually fluoresces. He worked out the biochemical reaction sequence that leads from the unfolded, inactive protein, via cyclisation, dehydration and oxidation of specific amino acids in the protein chain, to the modified, folded form that has the glowing report. Proteins from other species were found that glowed with different colours. However, genetic engineering of the amino acid sequence in GFP and these proteins can be used to tweak the amino acid sequence so that a different final chromophoric unit in the protein is produced that has a different emission spectrum and so glows with a different colour. There are now variants of GFP available to scientists that cover the whole of the visible spectrum.
A natural chemical prize
As with the chemistry prize of earlier years, the award has been made for basic research that turned out to have far-reaching implications and applications. On the surface, the work is biological in nature, but most certainly demonstrates chemical prowess at the fundamental level.
Living systems use tens of thousands of different proteins. Each controls at least one important biochemical process but when a single protein goes awry, the molecular machinery can fail, and illness and disease ensue. That is why it has been imperative for bioscience to map the role of different proteins in the body. Such insights will provide medicinal chemists and others with targets for therapeutic agents that repair, disable, or re-activate the errant proteins.
With the aid of GFP, researchers have developed ways to watch processes that were previously invisible, such as the development of nerve cells in the brain or how cancer cells spread. And, with the application of DNA technology, they can now connect GFP to otherwise invisible proteins. This glowing marker allows them to watch the movements, positions and interactions of the tagged proteins and how they respond to the presence of their natural target molecules, toxins, environmental pollutants, bacterial metabolites, and drug candidates.
A spectacular demonstration of just how far GFP technology had progressed within a few years of Tsien's pioneering work was done by researchers at Washington University School of Medicine in Missouri in 2000. They engineered mice to have red, green, yellow or cyan fluorescent proteins associated with different types of nerve cell. This rainbow of coloured tags was then used by others to follow the fate of cells in models of brain diseases such as Alzheimer's. The same approach can be applied to other tissues, such as the insulin-producing β-cells in the pancreas, which is important for understanding metabolic problems and diseases.
Looked at superficially, the 2008 Nobel Prize for chemistry may appear to be reward for a biological discovery. However, the inner workings of biological systems are built with molecular machinery, and so while the compounds may be natural, they are most definitely chemicals. | https://edu.rsc.org/news/nobel-chemists-get-the-green-light/2020710.article |
F.A. Fasola1 and A.J. Adekanmi2
- Department of Haematology, College of Medicine University of Ibadan. Nigeria.
- DDepartment of Radiology, College of Medicine University of Ibadan. Nigeria.
Abstract
Background: The spleen serves critical haematological and immunological functions in the body. However it is also the first organ to be affected by the effects of sickling in sickle cell anaemia. While the splenic size has been evaluated in sickle cell anaemia, the spleen sizes of these patients has not been associated with
any specific haematological pattern.
Objectives: To determine the haematological parameters of patients with sickle cell anaemia (SCA) in relation to spleen size.
Methods: The full blood count (FBC), the irreversibly sickled cells and blood transfusion use amongst SCA patients in steady state was evaluated. Abdominal ultrasound was also performed for all patients and HbAA control for splenic size categorization.
Results: Forty patients with SCA and 22 controls with HbAA were studied with mean age of 29.28 ± 8.10 years 28.23 ± 8.14 years respectively. The mean splenic longitudinal lengths in patients and controls were 6.3 ± 4.3cm and 8.9 ± 1.5 cm respectively (p-value < .05). The mean haematocrit and haemoglobin value were significantly lower in SCA cases than in controls (p < 0.001). Though the red cell indices were similar but the white blood cell and platelet count were significantly higher in patients than in controls. Among SCA cases, the spleen size showed significant positive correlation with haematocrit (r = 0.371, p = 0.019) and the age at 1st transfusion (r = 0.447, p = 0.013) but significant negative correlation with MCV, MCH, MCHC and platelet count. Above 80% of patients with severe, moderate and mild autosplenectomy had been transfused compared to 25% of patients with splenomegaly.
Conclusions: Similarities in red cell indices between patients and controls suggests an identical factor influencing the red cell indices which could be genetic such as thalassemia or environmental such as iron deficiency. The negative correlation of the spleen size with red cell indices, white cell count and platelet count and positive correlation with haematocrit suggest that spleen size can be used to determine clinical course of the disease. Earlier age at first transfusion, significantly higher frequency of blood transfusion and MCHC in patients with severe autosplenectomy suggest a more severe clinical course when compared with patients with splenomegaly, normal spleen, mild and moderate autosplenomegaly.
Keywords: Sickle cell anaemia, Splenic size, Autosplenectomy, Haematological parameters
Correspondence:
Dr. F.A. Fasola
Department of Haematology,
College of Medicine,
University of Ibadan,
Oyo State, Nigeria.
Email: [email protected]
Introduction
Sickle cell anaemia is characterized by hemolytic anemia and vaso-occlusion leading to acute and chronic tissue ischemia, infarction, chronic organ damage and organ dysfunction. One of the earliest organs to be affected by recurrent infarction and progressive damage is the spleen1. The spleen serves both haematological and immunological functions. Variability of haemoglobin level with splenomegaly has been documented in both peadiatric and adult sickle cell anaemia patients 2,3 with few documentations on autosplenectomy. Haematological functions of the spleen includes: erythropoiesis, maturation of the reticulocyte, lymphopoiesis, reservoir of blood cells, pitting and culling function and destruction of old red cells 4. The spleen presents a hypoxic, acidic and hypoglycemic environment for the erythrocytes resulting in sickled red cells due to the limited oxygen and glucose. The sickling leads to repeated infarctions of the spleen and subsequent reduction of both morphological size and function of the spleen. The splenic sizes in patients with sickle cell anaemia vary with the degree of insult it has received, thereby giving rise to a spectrum of sizes, from repeated infarction. One extreme is splenomegaly observed during infancy and early childhood, consequent to splenic sequestration or during adulthood due to increased demand on the spleen to perform its functions2,3. The other extreme is autosplenectomy which appears as a small wrinkled firm, nodular remnant following progressive atrophy due to repeated episodes of vaso-occlusion and infarction5.
The clinical and laboratory profile of patients with sickle cell anaemia are continuously being studied to understand the biology of the disease6,7. The haematological parameters are the most commonly requested investigation to determine the line of management, adjust therapy and predict outcome. The various types of SCD manifest considerable differences in haematological parameters8. These differences are further complicated by both physiological factors and acute or chronic complications. A change in the size of the spleen is a chronic complication which is postulated to affect haematological parameters and could also be associated with a unique clinical course. Paediatric patients with splenomegaly have lower mean haematocrit; retrospective analysis of their case files showed that these patients had predominantly anaemic crises while those without splenomegaly had had predominantly vaso-occlusive crises9,10. An enlarged spleen is rare in adults with sickle cell anaemia.11 Functional changes of the spleen is related to anatomic regression of the spleen11. The slower progression to atrophy is the result of a reduced tendency to sickling in vivo therefore adult sickle cell patients who retain their spleen are judged to have less severe clinical disease. However an inverse relationship between severity and autosplectomy has been reported when blood transfusion was used to determine clinical severity 12. A study by Awotua-Efebo et al showed that splenomegaly is associated with poorer haematological indices whilst autosplenectomy is associated with better indices.10 The transitory anatomic size of spleen between normal and autosplenectomy are not well recognized and studied. The patients with SCA require regular monitoring and evaluation for various reasons, therefore the knowledge of changes in haematological indices of patients induced by variation in splenic size may be useful in the management of patient. Most of the local literatures relating the spleen size to the haematological parameters have been in paediatric sickle cell anaemia patients and were not related to blood transfusion requirements13,14. The spleen in sickle patients in sub Saharan Africa is believed to be different from that of sickle cell patients outside sub Saharan Africa15. Therefore there is a need to generate local data to better understand the pathogeneses of the disease in our environment. This study aims to identify the link between haematological parameters, blood transfusion history and variations in spleen size of patients with sickle cell anaemia. | https://aipmed.org/?page_id=823 |
PQShield is a spinout from the University of Oxford specialising in post-quantum cryptography and cybersecurity. Our mission is to innovate and create solutions for the world’s most imminent security challenge: quantum computers. Our cryptosystems will ensure unparalleled internet security and data protection on a global scale across several industries – keeping us all safe as quantum computing technology develops.
Headquartered in Oxford, with additional teams across the UK and in the Netherlands, France, Belgium and the US, our quantum-secure cryptographic solutions work with companies’ legacy systems to protect devices and sensitive data now and for years to come. We are well-funded and VC backed, having recently closed our $20m series A funding round.
PQShield is a highly innovative deep tech company that considers our people to be our most important assets, and so our core value is to provide them with a work environment that promotes personal and professional growth. Hard work and loyalty are always met with acknowledgement, appreciation, and reward. We promote openness and flexibility, resulting in a friendly, family like environment.
Our corporate social responsibility centres around making sure our products are used in a constructive and positive way – we would like to think that our products will contribute to the greater good rather than be just another money-making commodity.
The role
PQShield is looking for an engineer or researcher to drive the operationalising of non-invasive side-channel security testing within the company. You will be responsible for building and maintaining shared infrastructure for FPGA and microcontroller based testing of side-channel secure cryptographic implementations. This includes managing the physical hardware (FPGA development boards, Oscilloscopes, host PCs), writing software which implements standard side-channel tests (TVLA, correlation power analysis) and orchestration of capturing power traces across hardware/software and co-designed implementations of cryptographic primitives. You will work closely with product teams to help them integrate these side-channel analysis flows into their projects. There is also considerable scope and freedom for research into how to effectively apply side-channel analysis techniques to new PQC algorithms. As a driver of PQC testing standards, you’d also interact with testing labs and standardization bodies on the practical aspects of side-channel testing for PQC implementation.
We’d expect you to have an understanding of:
- Side-channel analysis of symmetric cryptographic primitives (e.g. AES).
- Issues around secure embedded implementations of cryptography.
- Theoretical understanding of common side-channel countermeasures: hiding, masking (DOM, TI).
- Practical power and EM side-channel analysis implementation. Including but not limited to: target device communication, data storage, analysis techniques and optimizing for speed of analysis.
- Continuous integration and testing for hardware and software.
- FPGA development, specifically with the ChipWhisperer 305 platform.
- Microcontroller development (STM32 or similar platforms).
- Python and C language programming.
Other useful skills:
- Implementation of PQC algorithms, or an understanding of their main implementation issues.
- Understanding of pre-silicon simulation based trace collection.
- Excellent written and verbal communication skills.
- An enthusiasm for excellent documentation of code and deliverables.
- Understanding of computer architecture (ARM, RISC-V etc)
- Knowledge of standards for non-invasive side-channel testing (FIPS 140-3, ISO, Common Criteria).
- Use of Docker or similar tools to manage isolated access to shared hardware resources.
You’ll be working with a small and very productive team in the early stages of developing new IPs, with a chance to have a big impact on everything we do.
Apply for job
To view the job application please visit pqshield.com. | https://semiwiki.com/job/sca-analyst-infrastructure-engineer-2/ |
The paper "Adult Education Philosophy" is a wonderful example of a report on education. This is research in the field of adult education that is aimed at studying and analyzing the various aspects that are involved in the field. Such aspects include the understanding of philosophical orientation within the field. In order to understand one’ s philosophical orientation in the field, the aspects that must be looked at closely include personal values, ethics, intellectual traditions, and organizational values. All these aspects of the field are crucial in the mastering of the field of adult education.
This essay endeavors to provide a clear understanding and definition of what a personal philosophy of education entails (Zinn, 2010). It also intended to provide an outline of the importance of the relationship that exists between philosophy and education. The relationship between philosophy and educational practice is also a matter of concern in this study. Educational philosophy is a consistent and comprehensive set of beliefs that concern the teaching-learning transactions. An educational philosophy is crucial in helping educators in recognizing the need to think in a clear manner over what they are undertaking.
It is also the tool that enables them to see whatever they are engaged in a broader and larger context of social and individual development. A philosophy of education is essentially the aspect of getting individuals to think about their duties in their field of education. In doing this, educators have the ability to see the interaction that takes place among the various factors and elements that are involved in the teaching-learning interaction. Such elements include the administration, students, curriculum, and goals. Philosophy of education is abstract and just comprised of ideas.
It is interested in the overall principles of process, subject, object, or any phenomenon. It raises questions concerning what is to be done and why those actions or activities are to be done. It is more systematic and reflective rather than common sense. Philosophy of education is the aspect of thought that provides an avenue for crucial and more serious inquiry into traditions and ideas. Although the philosophy of education is theoretical, it is a set of belief systems that channels or drives the actions of an educator.
Consequently, one’ s personal philosophy of learning and teaching will function as the organizing structure that defines the individual’ s beliefs, attitudes, and values that are related to the exchange between teaching and learning (Zinn, 2010). Certain specific beliefs concerning life are applied to practice whenever the adult educator gets involved in the practice of education. The philosophy of education is composed of these beliefs. Beliefs on education provide some mechanism for the election of instructional content, the establishment of teaching and learning objectives, selection and/or development of instructional materials, interaction with students, and the evaluation of educational results and outcomes.
Education has the intent to cause change. This change can be in terms of an increase in skill, knowledge, or a change in behavior or attitude. The direction in which the change takes is defined, to a great extent, by what individuals and large groups in the society believe should occur through education. For instance, the early citizenship classes were designed in a manner that would facilitate the “ Americanization” of the immigrants. This was mainly to acculturate these individuals so that they could be able to fit better into American society.
Ethic pride in the American society was enhanced, instilled, and reinforced by the black studies classes that came up in the late 1960s. The teaching system of Maria Montessori was meant to encourage personal growth as opposed to the socializing of the children (Apps, 1985). | https://libraryofessays.com/report/what-is-my-philosophical-orientation-to-adult-education-2059780 |
Alphabet, which owns Google, announced on Friday (20) that it will lay off about 12,000 employees, joining other tech companies such as Amazon, Meta and Microsoft that have reduced their workforces recently.
Alphabet cuts headcount as the company faces a threat to its long-standing position at the top of the tech industry.
For years, the company has attracted the best talent to develop Google, YouTube and other products used by billions of users. Now it’s locked in competition with Microsoft in a burgeoning area known as generative artificial intelligence.
The cuts at Alphabet come two days after Microsoft said it would lay off 10,000 employees.
Alphabet CEO Sundar Pichai said in a statement to staff that the company has reassessed its products, people and priorities, which has led to job cuts across different geographies and products.
The workforce has expanded rapidly for better times, but now the company faces “a different economic reality”.
“The fact that these changes will impact the lives of Googlers weighs heavily on me, and I take full responsibility for the decisions that got us here,” said Pichai.
Alphabet’s job losses affect teams across the company, including recruiting and some corporate functions, as well as some engineering and product teams. The layoffs are global and affect the US team immediately.
According to the statement, Alphabet has already sent an email to affected employees. In other countries, the process will take longer due to local labor laws and practices.
The news comes during a period of economic uncertainty as well as technological promise. “I am confident of the enormous opportunity before us, thanks to the strength of our mission, the value of our products and services, and our first investments in AI,” said Pichai.
I have worked in the news industry for over 10 years and have been an author at News Bulletin 247 for the past 5 years. I mostly cover technology news and enjoy writing about the latest gadgets and devices. I am also a huge fan of music and enjoy attending live concerts whenever possible. | https://newsbulletin247.com/technology/250159.html |
Recommended Reads for Black History Month
There are so many ways to participate in Black History Month — volunteering, listening to audiobooks, podcasts, and attending virtual events — each having a unique way to communicate Black History to audiences of all ages and interests. Although learning about history, culture, and ongoing struggles should be a year-round pursuit, Black History Month gives many of us the reminder to actively engage in conversations and activities to honor and continue to learn more about Black history. Since many of us are still learning about diversity, equity, and inclusion, SMPS Oregon compiled a short list of books to peruse written by Black authors and featuring people of color as main characters.
This list ranges from contemporary fiction, to non-fiction and educational books for adults and children. It represents only a fraction of the books available on Black history and culture, with more books by authors of color in all genres to be found at some of your favorite retailers. Check out more Black History recommendations from Bookshop.org that also supports your local bookstores!
Nonfiction and Contemporary Fiction for Adults
Nonfiction for Kids
Have you recently read any books about Black History you’d like to share? Let us know! | https://smpsoregon.org/blog/id/125 |
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