Split (1)

train · 2.1M rows

title stringlengths 1 149 ⌀	section stringlengths 1 1.9k ⌀	text stringlengths 13 73.5k
Open carry in the United States	Demonstrations and events	On September 1, 2017 the state of Texas legalized the open carrying of blades longer than 5.5 inches in public.April 30, 2020 hundreds of protesters—many of them carrying guns—descended on the Michigan Capitol to oppose Gov. Gretchen Whitmer's extension of the state's stay-at-home order by another two weeks, to May 15. Protesters have demonstrated against stay-at-home orders at capitols in dozens of states, but the protests in Michigan were the starkest example yet of protesters actually entering a capitol while the legislature was in session and bringing weapons with them. Michigan is an open-carry state, however, and there are no rules barring people from bringing guns into the Capitol.
Open carry in the United States	Diversity in state laws	As of 2018, 45 states allowed open carry, but the details vary widely.
Open carry in the United States	Diversity in state laws	Four states, the Territory of the U.S. Virgin Islands and the District of Columbia fully prohibit the open carry of handguns. Twenty-five states permit open carry of a handgun without requiring the citizen to apply for any permit or license. Fifteen states require some form of permit (often the same permit as allows a person to carry concealed), and the remaining five states, though not prohibiting the practice in general, do not preempt local laws or law enforcement policies, and/or have significant restrictions on the practice, such as prohibiting it within the boundaries of an incorporated urban area. Illinois allows open carry on private property only.On October 11, 2011, California Governor Jerry Brown signed into law that it would be a "misdemeanor to openly carry an exposed and unloaded handgun in public or in a vehicle." This does not apply to the open carry of rifles or long guns or persons in rural areas where permitted by local ordinance.
Open carry in the United States	Diversity in state laws	On November 1, 2011, Wisconsin explicitly acknowledged the legality of open carry by amending its disorderly conduct statute (Wis. Stat. 947.01). A new subsection 2 states "Unless other facts and circumstances that indicate a criminal or malicious intent on the part of the person apply, a person is not in violation of, and may not be charged with a violation of, this section for loading, carrying, or going armed with a firearm, without regard to whether the firearm is loaded or is concealed or openly carried." On May 15, 2012, Oklahoma Governor Mary Fallin signed Senate Bill 1733, an amendment to the Oklahoma Self Defense Act, which will allow people with Oklahoma concealed weapons permits to open carry if they so choose. The law took effect November 1, 2012. "Under the measure, businesses may continue to prohibit firearms to be carried on their premises. SB 1733 prohibits carrying firearms on properties owned or leased by the city, state or federal government, at corrections facilities, in schools or college campuses, liquor stores and at sports arenas during sporting events."
Open carry in the United States	Federal Gun Free School Zones Act	The Federal Gun-Free School Zones Act of 1990 limits where a person may legally carry a firearm by generally prohibiting carry within 1,000 ft of the property line of any K–12 school in the nation, with private property excluded.In a 1995 Supreme Court case, the Act was declared unconstitutional (on Federalism, not Second Amendment grounds), but was reenacted in the slightly different form in 1996.
Open carry in the United States	Public opinion	According to joint polls published by CNN and the SSRS Institute: A majority of Americans support stricter gun control law; and 64% of Americans support stricter gun control laws, while 36% oppose it. Besides, 54% of Americans believe that such laws will reduce the number of deaths and killings of citizens with firearms, and 58% believe that the government can take effective action to prevent mass shootings.
Open carry in the United States	Public opinion	2023 According to a 2023 Fox News poll found registered voters overwhelmingly supported a wide variety of gun restrictions: 87% said they support requiring criminal background checks for all gun buyers; 81% support raising the age requirement to buy guns to 21; 80% support requiring mental health checks for all gun purchasers; 80% said police should be allowed take guns away from people considered a danger to themselves or others; 61% supported banning assault rifles and semi-automatic weapons.
HyperOs HyperDrive	HyperOs HyperDrive	HyperDrive (HD) is a series of RAM-based solid-state drives invented by Accelerated Logic B.V. (became Accelerated Logic ltd., and is now a German company) employee Pascal Bancsi (for HyperDrive II architecture), who partnered with the British company HyperOs Systems, who manufactured the retail product. The HyperDrive interfaces with and is recognized by computer systems as a standard hard drive.
HyperOs HyperDrive	HyperDrive I	Originally called 'Accelerator', development began in 1999. It is an IDE device supporting PIO mode 1 transfer, and includes 128 MiB SRAM.
HyperOs HyperDrive	HyperDrive II	After the SRAM Accelerator, it was switched to SDRAM, and uses 5.25-inch form factor, which allows the company to build Accelerator with capacity of 128 MiB to 4 GiB. It had maximum random access time of 0.15 ms. SDRAM was chosen over flash because of its speed advantage and reliability over flash memory.Later generations used 3.5-inch form factor and supports UDMA 33 transfer speed, with maximum capacity of 14 GiB.It uses Atmel controller.It includes battery backup mechanism.Future plans included support of UDMA66, Fibre Channel interface.
HyperOs HyperDrive	HyperDrive III	It uses Parallel ATA (PATA) (max 100 MB/s) or Serial ATA (SATA) interface. For the first time, memory capacity could be changed by using memory slots. It uses ECC DDR SDRAM (max 2 GiB per DIMM). Maximum capacity started at 6 DIMM (12 GiB), and was later changed to 8 DIMM (16 GiB). Non-volatile storage is achieved using an integral 160 minute 7.2 V battery backup battery (1250 mAh), external adapter, or HyperOs software. It uses the Xilinx Spartan FPGA and Atmel controller array. The circuit board was produced by DCE.
HyperOs HyperDrive	HyperDrive 4	It supports both SATA and PATA interfaces (PATA native), with interface speed up to 133 MB/s. It uses ECC DDR SDRAM (max 2 GiB per DIMM). Maximum capacity is 8 DIMM (16 GiB, PC1600-PC3200). Memory of different sizes can be mixed, but only if DIMMs of same capacity are used in 1 bank (4 DIMM/bank). It supports non-volatile memory backup using optional 2.5-inch PATA drive, HyperOs software (which swaps RAM contents to a different drive) or backup battery (5 Ah or 10 Ah). The drive is rated 125 MB/s data rate, 44k I/O per second. Revision 3 It supports registered ECC SDRAM, with capacity up to 2 GiB per DIMM on 16 GiB version and 4 GiB per DIMM on 32 GiB version. Seek time was reduced from 40 microseconds to 1100 nanoseconds read and 250 nanoseconds write. It also reduces the power consumption by 30% and employs gold plated DIMM sockets. HyperDrive 4 Rack-mounted It is a rack-mounted version of the device with at most four drives. HyperDrive 4 RAID Systems It is an external case version with four HyperDrive4 drives. It uses PCI-X or PCI Express x8 interface, with Silicon Image 3124 or Areca 12XX SAT RAID card to connect each drive.
HyperOs HyperDrive	HyperDrive 5	It uses SATA interface with 2x SATA2 interface ports. It uses DDR2 SDRAM (max 8 GiB per DIMM). The manufacturer claimed it had built-in ECC so it no longer required ECC memory, but ECC is performed at the expense of storage capacity if ECC memory is not used. Memory speed is not rated; the manufacturer recommends Kingston ValueRAM (PC2-3200 to PC2-6400).
HyperOs HyperDrive	HyperDrive 5	HyperDrive 5 includes 7.4 V 2400 mAh lithium battery for flash backup, CompactFlash card slot, with external DC adapter for non-volatile storage.
HyperOs HyperDrive	HyperDrive 5	The drive is rated 175 MB/s read, 145 MB/s write, 40k (later 65k) I/O per second, when using only one of the SATA2 links. The rated speed using the dual SATA2 links is not given by the manufacturer. When using both SATA2 links, the physical drive can be configured as a RAID 0 array with two devices with half of maximum capacity. In RAID 0 mode, the read and write speeds are reported to be more than twice those that are claimed by the manufacturer.Drive controller is switched to Taiwanese ASIC, instead of the Xilinx Spartan FPGA/Atmel array.
HyperOs HyperDrive	HyperDrive 5	HyperDrive 5 is also sold as ACard ANS-9010, outside of the UK. HyperDrive 5M A cheaper version of the Hyperdrive5, with only one SATA2 port and 6 DDR2 slots, so that memory is limited to 48 GiB. Performance and features are the same as the HyperDrive5 when using only one SATA2 link. HyperDrive 5M is sold as ACard ANS-9010B, outside of the UK.
HyperOs HyperDrive	Awards	HyperDrive4 (16 GiB) won Custom PCs Crazy But Cool award.
CHMP1A	CHMP1A	Charged multivesicular body protein 1a is a protein that in humans is encoded by the CHMP1A gene.
CHMP1A	Function	This gene encodes a member of the CHMP/Chmp family of proteins which are involved in multivesicular body sorting of proteins to the interiors of lysosomes. The initial prediction of the protein sequence encoded by this gene suggested that the encoded protein was a metallopeptidase. The nomenclature has been updated recently to reflect the correct biological function of this encoded protein.
CHMP1A	Interactions	CHMP1A has been shown to interact with VPS4A.
Moviola	Moviola	A Moviola () is a device that allows a film editor to view a film while editing. It was the first machine for motion picture editing when it was invented by Iwan Serrurier in 1924.
Moviola	History	Iwan Serrurier's original 1917 concept for the Moviola was as a home movie projector to be sold to the general public. The name was derived from the name "Victrola" since Serrurier thought his invention would do for home movie viewing what the Victrola did for home music listening. However, since the machine cost $600 in 1920 (equivalent to $8,800 in 2022), very few sold. An editor at Douglas Fairbanks Studios suggested that Iwan should adapt the device for use by film editors. Serrurier did this and the Moviola as an editing device was born in 1924, with the first Moviola being sold to Douglas Fairbanks himself.
Moviola	History	Many studios quickly adopted the Moviola including Universal Studios, Warner Bros., Charles Chaplin Studios, Buster Keaton Productions, Mary Pickford, Mack Sennett, and Metro-Goldwyn-Mayer. The need for portable editing equipment during World War II greatly expanded the market for Moviola's products, as did the advent of sound, 65mm and 70mm film.
Moviola	History	Iwan Serrurier's son, Mark Serrurier, took over his father's company in 1946. In 1966, Mark sold Moviola Co. to Magnasync Corporation (a subsidiary of Craig Corporation) of North Hollywood for $3 million. Combining the names, the new name was Magnasync/Moviola Corp. President L. S. Wayman instantly ordered a tripling of production, and the new owners realized their investment in less than two years.
Moviola	History	Wayman retired in 1981, and Moviola Co. was sold to J&R Film Co., Inc. in 1984. The Moviola company is still in existence and is located in Hollywood, where part of the facility is located on one of the original Moviola factory floors.
Moviola	Usage	The Moviola allowed editors to study individual shots in their cutting rooms, thus to determine more precisely where the best cut-point might be. The vertically oriented Moviolas were the standard for film editing in the United States until the 1970s, when horizontal flatbed editor systems became more common.
Moviola	Usage	Nevertheless, Moviolas continued to be used, albeit to a diminishing extent, into the 21st century. Michael Kahn received an Academy Award nomination for Best Film Editing in 2005 for his work on Steven Spielberg's Munich, which he edited with a Moviola, although by this time almost all editors had switched over to digital film editors (Kahn himself switched to digital editing for his later work).
Moviola	Awards	Mark Serrurier accepted an Academy Award of Merit (Oscar statue) for himself and his father for the Moviola in 1979. To MARK SERRURIER for the progressive development of the Moviola from the 1924 invention of his father, Iwan Serrurier, to the present Series 20 sophisticated film editing equipment. There is a star on the Hollywood Walk of Fame for Mark Serrurier because of the Moviola's contribution to Motion Pictures.
Average crossing number	Average crossing number	In the mathematical subject of knot theory, the average crossing number of a knot is the result of averaging over all directions the number of crossings in a knot diagram of the knot obtained by projection onto the plane orthogonal to the direction. The average crossing number is often seen in the context of physical knot theory.
Average crossing number	Definition	More precisely, if K is a smooth knot, then for almost every unit vector v giving the direction, orthogonal projection onto the plane perpendicular to v gives a knot diagram, and we can compute the crossing number, denoted n(v). The average crossing number is then defined as the integral over the unit sphere: 14π∫S2n(v)dA where dA is the area form on the 2-sphere. The integral makes sense because the set of directions where projection doesn't give a knot diagram is a set of measure zero and n(v) is locally constant when defined.
Average crossing number	Alternative formulation	A less intuitive but computationally useful definition is an integral similar to the Gauss linking integral. A derivation analogous to the derivation of the linking integral will be given. Let K be a knot, parameterized by f:S1→R3. Then define the map from the torus to the 2-sphere g:S1×S1→S2 by g(s,t)=f(s)−f(t)\|f(s)−f(t)\|.
Average crossing number	Alternative formulation	(Technically, one needs to avoid the diagonal: points where s = t .) We want to count the number of times a point (direction) is covered by g. This will count, for a generic direction, the number of crossings in a knot diagram given by projecting along that direction. Using the degree of the map, as in the linking integral, would count the number of crossings with sign, giving the writhe. Use g to pull back the area form on S2 to the torus T2 = S1 × S1. Instead of integrating this form, integrate the absolute value of it, to avoid the sign issue. The resulting integral is 14π∫T2\|(f′(s)×f′(t))⋅(f(s)−f(t))\|\|(f(s)−f(t))\|3dsdt.
Phosphosilicate glass	Phosphosilicate glass	Phosphosilicate glass, commonly referred to by the acronym PSG, is a silicate glass commonly used in semiconductor device fabrication for intermetal layers, i.e., insulating layers deposited between succeedingly higher metal or conducting layers, due to its effect in gettering alkali ions. Another common type of phosphosilicate glass is borophosphosilicate glass (BPSG). Soda-lime phosphosilicate glasses also form the basis for bioactive glasses (e.g. Bioglass), a family of materials which chemically convert to mineralised bone (hydroxy-carbonate-apatite) in physiological fluid. Bismuth doped phosphosilicate glasses are being explored for use as the active gain medium in fiber lasers for fiber-optic communication.
CA/EZTEST	CA/EZTEST	CA-EZTEST was a CICS interactive test/debug software package distributed by Computer Associates and originally called EZTEST/CICS, produced by Capex Corporation of Phoenix, Arizona with assistance from Ken Dakin from England.The product provided source level test and debugging features for computer programs written in COBOL, PL/I and Assembler (BAL) languages to complement their own existing COBOL optimizer product.
CA/EZTEST	Competition	CA-EZTEST initially competed with three rival products: "Intertest" originally from On-line Software International, based in the United States. In 1991, Computer Associates International, Inc. acquired On-line Software and renamed the product CA-INTERTEST, then stopped selling CA-EZTEST. OLIVER (CICS interactive test/debug) from Advanced Programming Techniques in the UK. XPEDITER from Compuware Corporation who in 1994 acquired the OLIVER product.
CA/EZTEST	Early critical role	Between them, these three products provided much needed third-party system software support for IBM's "flagship" teleprocessing product CICS, which survived for more than 20 years as a strategic product without any memory protection of its own. A single "rogue" application program (frequently by a buffer overflow) could accidentally overwrite data almost anywhere in the address space causing "down-time" for the entire teleprocessing system, possibly supporting thousands of remote terminals. This was despite the fact that much of the world's banking and other commerce relied heavily on CICS for secure transaction processing between 1970 and early 1990s. The difficulty in deciding which application program caused the problem was often insurmountable and frequently the system would be restarted without spending many hours investigated very large (and initially unformatted) "core dump"s requiring expert system programming support and knowledge.
CA/EZTEST	Early integrated testing environment	Additionally, the product (and its competitors) provided an integrated testing environment which was not provided by IBM for early versions of CICS and which was only partially satisfied with their later embedded testing tool — "Execution Diagnostic Facility" (EDF), which only helped newer "Command level" programmers and provided no protection.
CA/EZTEST	Supported operating systems	The following operating systems were supported: IBM MVS IBM XA IBM VSE (except XPEDITER)
Unnoticed Art	Unnoticed Art	Unnoticed Art is the name of an organisation and a series of initiatives relating to a form of performance art that is executed in a non-theatrical context.The term 'Unnoticed Art' was originally mentioned by Dutch artist Frans van Lent as a basic concept for the first Unnoticed Art Festival, which took place in Haarlem (The Netherlands) in 2014. The first Unnoticed Art Festival took place over two days, during which time thirty volunteers executed the performance scores created by thirty five artists. An iteration of the first Unnoticed Art Festival was commissioned by Zeppelin University in Friedrichshafen in Germany to form part of their 2014 Sommerfest, the university's principal annual public engagement event. This used a selection of works devised for the Haarlem event. The second Unnoticed Art Festival took place in Nijmegen, 2016. The book Unnoticed Art was published in January, 2015. It contains an artistic statement by Frans van Lent and a catalogue of the Unnoticed Art Festival performances.
Unnoticed Art	Unnoticed Art	The 'Unnoticed Art' concept was further developed into a blog titled UnnoticedArt.com. The purpose of this blog is to present a wide variety of art works that relate to the artistic attitude of the field of Unnoticed Art. In addition, TheConceptBank.org was initiated as a follow up from the first Unnoticed Art Festival, as an online free approachable database for performative concepts. Like the festival, TheConceptBank.org is based on the separation of concept creation (the artist) and execution (by visitors of the website). This website was launched in May 2014. Another derivation of the 'Unnoticed Art' concept, The ParallelShow, is recognised as a series of impromptu performances of occasional collaborations from performance art practitioners. It started on 7 July 2015 as a singular occasion at the Kunsthal in Rotterdam, NL. This first ParallelShow was a cooperation of three Dutch artists: Ieke Trinks, Ienke Kastelein and Frans van Lent.
Unnoticed Art	Unnoticed Art	The concept of The ParallelShow took place unexpectedly at and around public exhibitions in art venues. It was never announced, no invitations are ever sent. Since the first show, The ParallelShow has also been initiated in nine other locations: 23 October 2015: at the Naturalis Biodiversity Center in Leiden, Netherlands; 4 December 2015: at the M-Museumin Leuven, Belgium; 17 January 2016: at the Tate Britain, London, UK; 11 February 2016: at the Art Rotterdam art-fair, Rotterdam, Netherlands; 28 May 2016: at the Archeological Sites, Delphi, Greece; 5 June 2016: at the Huis van Gijn, Dordrecht, Netherlands; 18 September 2016: at the Institut Valencià d’Art Modern (IVAM), Valencia, Spain; 6 November 2016: at the Stasi Museum, Berlin, Germany; 8 January 2017: at the Met Cloisters, in New York City, New York, USA.The ParallelShow never leaves any physical traces of its occurrence.
Unnoticed Art	Unnoticed Art	The ParallelShow book was published from Jap Sam Books, in The Netherlands, in March 2018.
Nuclear utilization target selection	Nuclear utilization target selection	Nuclear utilization target selection (NUTS) is a hypothesis regarding the use of nuclear weapons often contrasted with mutually assured destruction (MAD). NUTS theory at its most basic level asserts that it is possible for a limited nuclear exchange to occur and that nuclear weapons are simply one more rung on the ladder of escalation pioneered by Herman Kahn. This leads to a number of other conclusions regarding the potential uses of and responses to nuclear weapons.
Nuclear utilization target selection	Counterforce strikes	A counterforce strike consists of an attack on enemy nuclear weapons meant to destroy them before they can be used. A viable first strike capability would require the ability to launch a 100-percent-effective (or nearly so) counterforce attack. Such an attack is made more difficult by systems such as early warning radars which allow the possibility for rapid recognition and response to a nuclear attack and by systems such as submarine-launched ballistic missiles or road-mobile nuclear missiles (such as the Soviet SS-20) which make nuclear weapons harder to locate and target.
Nuclear utilization target selection	Counterforce strikes	Since a limited nuclear war is a viable option for a NUTS theorist, the power to unleash such attacks holds a great deal of appeal. However, establishing such a capability is very expensive. A counterforce weapon requires a much more accurate warhead than a countervalue weapon, as it must be guaranteed to detonate very close to its target, which drastically increases relative costs.
Nuclear utilization target selection	Limited countervalue strikes	Some NUTS theorists hold that a mutually assured destruction-type deterrent is not credible in cases of a small attack, such as one carried out on a single city, as it is suicidal. In such a case, an overwhelming nuclear response would destroy every enemy city and thus every potential hostage that could be used to influence the attacker's behavior. This would free up the attacker to launch further attacks and remove any chance for the attacked nation to bargain. A country adhering to a NUTS-style war plan would likely respond to such an attack with a limited attack on one or several enemy cities.
Nuclear utilization target selection	Missile defense	Since NUTS theory assumes the possibility of a winnable nuclear war, the contention of many MAD theorists that missile defense systems should be abandoned as a destabilizing influence is generally not accepted by NUTS theorists. For NUTS theorists, a missile defence system would be a positive force in that it would protect against a limited nuclear attack. Additionally, such a system would increase the odds of success for a counterforce attack by assuring that if some targets escaped the initial attack, the incoming missiles could be intercepted. But protection against a limited attack means that the opponent has incentive to launch a larger scale attack, against which the defence is likely to be ineffective. Additionally, increased possibility of success of counterforce attacks means that the opponent has the incentive to launch a preventive attack, which increases the risk of a large scale response to misinterpreted signals.
Nuclear utilization target selection	NUTS and US nuclear strategy	NUTS theory can be seen in the US adoption of a number of first-strike weapons, such as the Trident II and Minuteman III nuclear missiles, which both have an extremely low circular error probable (CEP) of about 90 meters for the former and 120 meters for the latter. These weapons are accurate enough to almost certainly destroy a missile silo if it is targeted.
Nuclear utilization target selection	NUTS and US nuclear strategy	Additionally, the US has proceeded with a number of programs which improve its strategic situation in a nuclear confrontation. The Stealth bomber has the capacity to carry a large number of stealthy cruise missiles, which could be nuclear-tipped, and due to its low probability of detection and long range would be an excellent weapon with which to deliver a first strike.During the late 1970s and the 1980s, the Pentagon began to adopt strategies for limited nuclear options to make it possible to control escalation and reduce the risk of all-out nuclear war, hence accepting NUTS. In 1980, President Jimmy Carter signed Presidential Directive 59 which endorsed the NUTS strategic posture committed to fight and win a nuclear war, and accepted escalation dominance and flexible response. The Soviets, however, were skeptical of limited options or the possibility of controlling escalation. While Soviet deterrence doctrine posited massive responses to any nuclear use ("all against any"), military officials considered the possibility of proportionate responses to a limited US attack, although they "doubted that nuclear war could remain limited for long."Like several other nuclear powers, but unlike China and India, the United States has never made a "no first use" pledge, maintaining that pledging not to use nuclear weapons before an opponent would undermine their deterrent. NATO plans for war with the USSR called for the use of tactical nuclear weapons in order to counter Soviet numerical superiority.
Nuclear utilization target selection	NUTS and US nuclear strategy	Rather than making extensive preparations for battlefield nuclear combat in Central Europe, the Soviet General Staff emphasized conventional military operations and believing that they had an advantage there. "The Soviet military leadership believed that conventional superiority provided the Warsaw Pact with the means to approximate the effects of nuclear weapons and achieve victory in Europe without resort to those weapons."In criticising US policy on nuclear weapons as contradictory, leftist philosopher Slavoj Zizek has suggested that NUTS is the policy of the US with respect to Iran and North Korea while its policy with respect to Russia and China is one of mutual assured destruction (MAD).
Gazelle (web browser)	Gazelle (web browser)	Gazelle was a research web browser project by Microsoft Research, first announced in early 2009. The central notion of the project was to apply operating system (OS) principles to browser construction. In particular, the browser had a secure kernel, modeled after an OS kernel, and various web sources run as separate "principals" above that, similar to user space processes in an OS. The goal of doing this was to prevent bad code from one web source to affect the rendering or processing of code from other web sources. Browser plugins are also managed as principals.Gazelle had a predecessor project, MashupOS, but with Gazelle the emphasis was on a more secure browser.By the July 2009 announcement of ChromeOS, Gazelle was seen as a possible alternative Microsoft architectural approach compared to Google's direction. That is, rather than the OS being reduced in role to that of a browser, the browser would be strengthened using OS principles.The Gazelle project became dormant, and ServiceOS arose as a replacement project also related to browser architectures. But by 2015, the SecureOS project was also dormant, after Microsoft decided that its new flagship browser would be Edge.
Epigenetics of human development	Epigenetics of human development	Epigenetics of human development is the study of how epigenetics (hertiable characteristics that do no involve changes in DNA sequence) effects human development.
Epigenetics of human development	Epigenetics of human development	Development before birth, including gametogenesis, embryogenesis, and fetal development, is the process of body development from the gametes are formed to eventually combine into a zygote to when the fully developed organism exits the uterus. Epigenetic processes are vital to fetal development due to the need to differentiate from a single cell to a variety of cell types that are arranged in such a way to produce cohesive tissues, organs, and systems.
Epigenetics of human development	Epigenetics of human development	Epigenetic modifications such as methylation of CpGs (a dinucleotide composed of a 2'-deoxycytosine and a 2' deoxyguanosine) and histone tail modifications allow activation or repression of certain genes within a cell, in order to create cell memory either in favor of using a gene or not using a gene. These modifications can either originate from the parental DNA, or can be added to the gene by various proteins and can contribute to differentiation. Processes that alter the epigenetic profile of a gene include production of activating or repressing protein complexes, usage of non-coding RNAs to guide proteins capable of modification, and the proliferation of a signal by having protein complexes attract either another protein complex or more DNA in order to modify other locations in the gene.
Epigenetics of human development	Definitions	Gene expression refers to the transcription of a gene but the RNA produced does not necessarily have to encode a protein product. Transcription may produce so called noncoding RNA products such as tRNA and regulatory RNA. Repression may refer to the decrease in transcription of a gene or inhibition of a protein. Proteins are often inhibited by binding the active site or causing a conformational change so that the active site can no longer bind. By making these alterations, proteins, like transcription factors, may bind DNA less or some protein may be inhibited so that it becomes a block in a signaling cascade and certain genes will then not be induced to be expressed. Repression can occur pre- or post-transcriptionally. Methylating the DNA or the modifying the histones that the DNA wraps around is one example that commonly leads to repression. Pre-transcriptional repression can also occur by altering the proteins that allow transcription to occur, namely the polymerase complex. Proteins can sit on the DNA strand and serve as a kind of block to polymerase proteins, halting them from transcribing. Post-transcriptional repression generally refers to the degradation of the RNA product or binding the RNA with proteins so that it cannot be translated or carry out its function.
Epigenetics of human development	Definitions	DNA methylation in humans and most other mammals refers to the methylation of a CpG. Methylation of these cytosines are common in DNA, and in sufficient numbers can prevent proteins from attaching to the DNA by obscuring the domain binding site's matching DNA to the protein. Regions in which cytosines prior to guanines are clustered and highly unmethylated are called CpG islands, and often serve as promoters, or transcription start sites.
Epigenetics of human development	Definitions	Histone modifications are modifications made to the amino acid residues in the tails of the histones that either restrict the histone's ability to bind to DNA or boost the histone's ability to bind to DNA. Histone modifications also act as sites for proteins to attach, which then further alter the gene's expression. Two common histone modifications are acetylation and methylation. Acetylation is when a protein adds an acetyl group to a lysine in a histone tail in order to restrict the ability of the histone to bind to DNA. This acetylation is commonly found on lysine 9 of histone 3, notated as H3K9ac. This results in the DNA being more open to transcription, due to the decreased binding to the histone. Methylation, meanwhile, is when a protein adds a methyl group to a lysine in a histone tail, although more than one methyl group can be added at a time. Two sites for histone methylation are common in current studies: trimethylation of lysine 4 on histone 3 (H3K4me3), which causes activation, and trimethylation of lysine 27 on histone 3, which causes repression (H3K27me3).
Epigenetics of human development	Definitions	Cis acting elements refer to mechanisms that act on the same chromosome they come from, usually either in the same region from which they were produced or a region very close to this origin region. For example, a long non-coding RNA that is produced at one location silences the same or a different location on the same chromosome. Trans acting elements, however, are gene products from one location that act on a different chromosome, either the other in a chromosomal pair, or on a different chromosome from a separate chromosome pair. An example of this is a long non coding RNA from Hox gene C silences Hox gene D on a different chromosome, from a different chromosomal pair.
Epigenetics of human development	Hox gene regulation	Hox genes are genes in humans that regulate body plan development. Humans have four sets of Hox genes, numbering 39 genes altogether, all of which aid in the differentiation of cells by location. Hox genes are activated early in the development of the embryo, in order to plan the development of the differing structures of the body. They also show colinearity with the body plan, meaning that the order of the Hox genes is similar to the expression levels of the Hox genes on the anterior-posterior axis. This colinearity allows for a spatial and temporal activation of genes in order to produce a proper body structure.Hox genes are regulated using a variety of epigenetic mechanisms, including the use of lncRNAs such as HOTAIR, the Trithorax (TrxG) group of proteins, and the Polycomb (PcG) group of proteins.
Epigenetics of human development	Hox gene regulation	In Hox genes, long non-coding RNAs allow for communication between different Hox genes and different sets of Hox genes in order to coordinate body plan in the cell. One example of a long non-coding RNA that coordinates between Hox gene sets is HOTAIR, which is an RNA transcript produced in the HoxC cassette that represses transcription of a large number of genes in the HoxD cassette. Thus, HOTAIR regulates the HoxD genes from the HoxC genes in order to coordinate transcription of the Hox genes.
Epigenetics of human development	Hox gene regulation	Role of PcG and TrxG The PcG and TrxG genes that produce protein complexes responsible for continuing the activation and the repression patterns in the Hox genes initially formed by the maternal factors. PcG genes are responsible for repressing chromatin in Hox clusters meant to be inactivated in the differentiated cell. PcG proteins repress genes by forming polycomb repressive complexes, such as PRC1 and PRC2. PRC2 complexes repress by trimethylating histone 3 at lysine 27 through histone methyltransferases Ezh2 and Ezh1. PRC2 is recruited by many elements, including CpG islands. PRC1, meanwhile, ubiquitinates H2AK119 using Ring1A/B's E3 ligase activity, causing stalling of RNA polymerase II. Furthermore, Ring1B, a member of the PRC1 complex, also represses Hox genes with Me118, Mph2, and RYBP by compacting the chromatin into higher-order structures. TrxG genes, meanwhile, are responsible for activating genes by trimethylating lysine 4 of the histone H3 tail. Genes with similar transcriptional marks tend to cluster together in distinct structures. In bivalent domains, both of these marks are present, indicating genes that are silenced but can be rapidly activated when necessary.
Epigenetics of human development	Hox gene regulation	Role of ncRNAs 231 ncRNAs are present in the four Hox gene cassettes. Similarly to the Hox protein-coding genes, the ncRNAs show differential expression according to the cell's location on the anterior-posterior and proximal-distal axes. These lncRNAs can act either on the set of genes which they are present in, or can act on a separate gene set within the Hox genes.HOTTIP is a long non-coding RNA that assists in regulating the HoxA genes. It is produced from the 5' end of the HoxA gene cassette, and activates HoxA genes. Loops within the chromosome bring HOTTIP closer to its targets; this allows HOTTIP to bind to WDR5/MLL protein complexes to aid in trimethylation of lysine 4 of histone 3.HOTAIR is a long non-coding RNA that assists in regulating the HoxD genes. It is produced in the HoxC cassette, near the divide between expressed and unexpressed genes, and represses HoxD genes. HOTAIR acts by attaching to Suz12 in the PRC2 complex, and then guides this complex to the genes to be repressed. PRC2 then trimethylates the lysine 27 of histone 3, repressing the gene of interest.
Epigenetics of human development	Barr body formation	In female humans, Barr bodies are defined as the condensed and inactivated X-chromosome that is found in every cell of the adult. Because females have two nearly identical X chromosomes, one of them must be silenced so that the expression levels of the genes on the X-chromosome are of the proper dosage. Thus, males and females have the same level of X-chromosome expression, despite being born with one X for males and two for females. This is also why individuals with Klinefelter syndrome, a disease in which more than two sex chromosomes are present in the body, have fewer symptoms than individuals with other types of aneuploidy, which are often fatal before birth.
Epigenetics of human development	Barr body formation	The role of Xist Inactivation of one of the X chromosomes is initiated by a long non coding RNA called Xist. This lncRNA is expressed on the same chromosome it represses, known as working in cis. Recent research has shown that a repeat element in the RNA of Xist causes PRC2 to bind to the RNA. Another part of the RNA binds to the X-chromosome positioning PRC2 such that it can methylate various regions on the X-chromosome. This methylation causes other factors like histone deacetylases (HDACs) to bind to the chromosome and propagate heterochromatin formation, even into active gene regions. This heterochromatin greatly reduces, if not completely silences gene expression of the Barr body. Xist will be continuously created to maintain a condensed and silenced Barr body.In human cells with more than one X chromosome, two long non-coding RNAs are produced: Tsix is produced by one X chromosome, and Xist is produced by all of the other X chromosomes. Tsix is a long non-coding RNA that prevents repression of an X chromosome, while Xist is a long non-coding RNA that acts to repress and condense an entire X chromosome. The actions of Xist serve to create a Barr body in the cell.
Epigenetics of human development	Barr body formation	Random early X-chromosome inactivation In embryonic development, when the zygote is still composed of just a few cells, each cell of the zygote will randomly choose an X-chromosome to condense and silence. From then on, the daughter cells of that cell will always silence the same X-chromosome as the parent cell it propagated from. This creates what is known as the “mosaic effect,” in which differential X-chromosome expression creates differing genotypes throughout a single organism. This may or may not be evident in females, depending on how the genes of the X-chromosomes affect phenotype. If the alleles for a gene are identical on both X-chromosomes, then you will see no difference between the cells that chose one X over the other. If the alleles are different for, say, fur color, then you may see patches of one color and patches of the other color. In calico cats the mosaic pattern of X inactivation is easily seen because a gene affecting coat color is carried on the X, resulting in patches of color on the coat. The mosaic pattern of X inactivation may also determine how penetrant a disease is, if the disease allele is present on one X-chromosome and not the other. The organism may have few cells in which the diseased allele has not been condensed, leading to little expression of the disease allele. This is referred to as skewed X-chromosome inactivation.
Epigenetics of human development	Imprinting	Imprinting is defined as the differential expression of paternal and maternal alleles of a gene, due to epigenetic marks introduced onto the chromosome during the production of egg and sperm. These marks usually lead to differential expression of the specific sets of genes from the maternal and paternal chromosomes. Imprinting is carried out through many epigenetic mechanisms like methylation, histone modifications, rearrangement of higher order chromatin structure, non-coding RNAs, and interfering RNAs.
Epigenetics of human development	Imprinting	Function A single evolutionary purpose of imprinting is still unknown, since the mechanisms and effects seem to be so diverse. One hypothesis states that imprinting occurs in order to carry out the evolutionary goal of the parent, that being the differential partition of resources. The male seeks to provide maximum resources for his offspring so that his genes may be passed on successfully to the next generation, whereas the female must partition resources between all her offspring, and so must limit resources given.Another hypothesis states that imprinting may help protect the female from ovarian trophoblastic disease and parthenogenesis. Trophoblastic disease occurs when a sperm fertilizes an egg with no nucleus and a cancer-like mass forms in the placenta. Parthenogenesis occurs when an unfertilized egg develops into a fully functional organism that is genetically identical to the parent, who is female in the case of animals or both sexes, in the case of plants. This does not occur naturally in mammals. In most animals, especially mammals, uniparental inheritance of chromosomes is often lethal or results in developmental abnormalities, sometimes physically but often cognitively. Other hypotheses point to the function of imprinting as a way of establishing the proper amount of expression or functional haploidy, much like silencing the extra X-chromosome in females (see section on Barr bodies). Imprinting may help in the differentiation of cells by silencing pluripotency genes or other developmental genes. Supporting this hypothesis, imprinted genes have been shown to differ in their expression between tissue types in the same organism, pointing to divergent outcomes as a result of developmental events during embryogenesis. Regardless of whether there is a single purpose for imprinting, numerous studies have shown that a normal and functional organism cannot be made without the various imprinting mechanisms.
Epigenetics of human development	Imprinting	Igf2 and H19 In mammals, imprinted genes are often clustered in the genome, probably because they share transcriptional regulators or regulatory regions that impact the expression of multiple genes. It is easier for a lncRNA to silence multiple genes if they are closer together, making silencing more efficient. In some cases, when a gene is transcribed it overlaps another region nearby or opposite (antisense) to it, often silencing it. In the case of the Ifg2 and H19 genes, CTCF, a transcriptional repressor protein, is involved. CTCF binds to the unmethylated maternal ICR region but not the methylated paternal ICR region. ICR is a shared control region of Ifg2 and H19 that, when deleted, results in the loss of imprinting of these genes. CTCF then binds another region of the chromosome, creating a loop where Igf2 is blocked from transcription, but H19 is not, resulting in the maternal chromosome expressing H19 but not Igf2. CTCF has been shown to directly interact with Suz12, a subunit of PRC2, in order to silence the Ifg2 promoter region through hypermethylation. Conversely, the paternal H19 promoter is highly methylated during embryogenesis so that Ifg2 will not be silenced. Should CTCF fail to bind, H19 on the maternal chromosome has reduced expression and Igf2 is not silenced properly, resulting in biallelic expression. Mice have homologues of these genes, but silence them in a different way, where biallelic expression occurs and then antisense RNA is used to silence one of the genes.
Epigenetics of human development	Imprinting	Igf2r and Airn Airn is an lncRNA used to silence Igf2r and other surrounding genes. In the mechanism to silence Igf2r, the transcription of the lncRNA Airn silences the expression of Igf2r, as opposed to an active repression mechanism. Airn is the antisense gene of Ifg2r, so if Airn is being transcribed, the transcriptional machinery may cover a part of or the entire promoter region of Igf2r, so RNA polymerase cannot bind to the promoter region of Igf2r in order to initiate transcription. This mechanism is very efficient in that Igf2r is silenced by transcription of Airn, while the RNA product silences other genes near Igf2r. The imprinting mechanisms described above work on the chromosome that the Airn lncRNA is produced, but there are many other imprinted genes that work to silence genes on other chromosomes or to silence the similar allele(s) on the opposing chromosome of the same pair. Some imprinted genes code for regulatory RNA elements such as lncRNA, small nucleolar RNA, and micro RNA, so the expression of these genes results in the silencing of some other gene.From these examples, researchers have seen similar patterns in developmental genetics. It is imperative that many genes are silenced at the right time so that cells can maintain their identity and expressional integrity. Failure to do so often leads to symptoms such as cognitive abnormalities, if not fatality.
Epigenetics of human development	Imprinting	Igf2r regulation The lncRNA Airn is an lncRNA that regulates Igf2r expression. Igf2r is a gene which expresses a receptor for insulin-like growth factor 2, and assists in lysosomal enzyme transport, activation of growth factors, and degradation of insulin-like growth factor 2. This lncRNA is an RNA modified by imprinting, leading to Airn expression in the paternal allele, but not in the maternal allele. Airn acts by cis-acting silencing of the Igf2r region through overlapping the Igf2r gene through the antisense transcript encoded by Airn. Airn is silenced in the maternal allele through Igf2r transcription. In the brain, however, Igf2r alleles are both expressed due to Airn mediation being repressed in neuronal cells.
Epigenetics of human development	Role of PRC2	PRC2 (Polycomb Repressive Complex 2) is a complex of proteins that repress chromatin by histone methylation and by working to recruit other proteins that help further the repression of chromatin. The structure of this complex and group of mechanisms used by this complex are highly conserved across various eukaryotic species. Very few species have duplicates of these complexes in the genome beyond PRC1 and PRC2.
Epigenetics of human development	Role of lncRNAs	Long non-coding RNAs, or lncRNAs, are RNA transcripts produced by RNA polymerase II that are not translated but participate in the regulation of gene expression. Long non-coding RNAs are used in various epigenetic processes in development, including the regulation of Hox genes, as well as in the creation of Barr bodies.
Epigenetics of human development	Role of lncRNAs	Recruitment by lncRNA Although PRC2 seems to have a very simple mechanism and works on many genes and chromosomes across the genome, it often has very specific binding regions and has been observed to localize to specific genes to cause their repression. Recent research shows that it probably does this through the binding of long non coding RNAs (lncRNAs). Xist and Hox genes have both been studied extensively and display this mechanism very well. The lncRNA that the complex binds does not necessarily need to hybridize to the target region in order to silence it, as evidenced by the PRC2-lncRNA complex working on regions other than the region from which this complex was produced. However, the three-dimensional configuration of the RNA often gives the complex specific localization to regions where the RNA is created to bind.
Epigenetics of human development	Role of lncRNAs	Repressive function PRC2 is a multi-protein complex composed of four major subunits (E2H1/2, SUZ12, EED, and RbAp46/48) and three variable subunits (AEBP2, JARID2, and PCLs). The three variable subunits are used for catalysis of enzymatic reactions or binding to specific regions, not for repression of genes or chromatin. Similar to a zinc finger, AEBP2 docks onto the major grooves of DNA to assist in binding. PRC2 is usually recruited by other proteins or lncRNa and then catalyzes the trimethylation of lysine 27 of histone 3 tails (H3K27me3. This methylation is thought to cause repression by steric hindrance of RNA polymerase II. Even though the polymerase is not prevented from binding, the polymerase, after beginning transcription, will pause at H3K27me3 marks. The short transcript produced by the pausing of the polymerase often recruits regulatory complexes, like PRC2. Thus, PRC2 represses by two mechanisms: by directly altering the structure of the chromatin through methylation or by binding of transcripts.
Epigenetics of human development	Role of lncRNAs	Phosphorylation PRC2 has been shown in many experiments to be necessary for the proper formation of organs, starting with the maintenance of cellular differentiation and silencing of pluripotency genes. The exact mechanism in early embryogenesis that induces cells to differentiate is still unclear, but this mechanism has been closely linked to protein kinase A (PKA). Since the PRC2 complex has sites able to be phosphorylated and has differentiated behavior based on the level of phosphorylation, a logical hypothesis can be made that PKA affects PRC2 behavior and may phosphorylate PRC2, activating the protein and starting the methylation cascade that silences genes.
Epigenetics of human development	Role of lncRNAs	Early cell differentiation Experimentally, PRC2 has been shown to be highly enriched at the Hox genes and near developmental gene regulators, resulting in their methylation. Some time after the second or third cleavage event, PRC2 begins to bind to these developmental genes, even though they have the markers for highly active genes like H3K9me3. This has been described as the “leaking” of PRC2 binding. Variable binding will cause some genes to be silenced before others, causing differentiation, but this is likely regulated by the organism. What causes the specificity of cell differentiation is still unknown but some hypotheses say it largely has to do with the cell environment and the “awareness” of the cells to each other, considering all cells in this stage contain identical genomes at this point. The maintained cell lines after this differentiation event are largely dependent on PRC2. Without it, pluripotency genes will still be active, causing the cells to be unstable and reversion back to a stem cell-like stage where the cell would have to undergo differentiation again in order to return to its normal state. Properly differentiated cells have silenced pluripotency genes.
Epigenetics of human development	Role of lncRNAs	Maintenance of chromosome condensation PRC2 is also highly associated with intergenic regions, subtelomeric regions, and long-terminal repeat transposons. PRC2 acts to create heterochromatin in these regions through similar mechanisms to the mechanism used to repress genes. Heterochromatin formation is imperative in these regions in order to regulate gene expression, maintain chromatin shape, prevent degradation of the chromosome, and reduce the event of transposon “hopping” or spontaneous recombination.Thus, PRC2 is not only essential to the initiation of differentiation in development, but also for maintaining heterochromatin in all cell stages and for silencing genes and chromosome regions that would undo the cell differentiation that had already occurred or negatively affect the survival of the cell or the organism as a whole.
Epigenetics of human development	Role of lncRNAs	Paraspeckle formation Neat1 is an lncRNA which assists in forming the structure of nuclear structures known as paraspeckles: nuclear bodies which contain RNA-binding proteins. They control gene expression in the nucleus by retaining RNA in the nucleus that would otherwise alter gene expression. Paraspeckles form a significant portion of the corpus luteum of the ovary; in Neat1 impaired mice, corpus luteum formation is highly dysfunctional, causing ovarian defects and lowered progesterone levels resulting in a lack of pregnancy in Neat1 deficient mice. Neat1 assists in regulation of luteal genes by preventing the protein Sfpq from inhibiting Nr5a1 and Sp1, allowing luteal genes to be regularly transcribed. Neat1 is regulated by histone deacetylases.
Epigenetics of human development	Role of lncRNAs	Neuronal differentiation Evf2 is a lncRNA that acts in forebrain neuronal differentiation during embryonic development. Evf2 is transcribed from an ultraconserved region, or a region that is very highly conserved among most vertebrate species, within the region from Dlx5 to Dlx6. This region is a target for SHH, a highly important regulator of central nervous system development. Evf2, when transcribed, recruits Dlx and Mecp2 through cis and trans-acting mechanisms to the Dlx5/6 region in the ventral forebrain, causing GABAergic interneurons in the hippocampus to be formed. Evf2 acts by forming a complex with Dlx4 that increases Dlx4 transcription activation ability and stability.Malat1, another neurological lncRNA, causes increased synaptic function and greater amounts of dendrite development. Increases of Malat1 increase neuronal density, while decreases of Malat1 decrease neuronal density. Malat1 acts by regulating the expression levels of Nlgn1 and SynCAM1 which are important genes in synapse formation.
Epigenetics of human development	Role of BRD4	Bromodomain protein 4, or BRD4, is a protein which binds to acetylated tails of histones H3 and H4 to aid active gene transcription by decompaction using the bromodomain with the assistance of the acetylated K5 on H4. BRD4 is a member of the BET protein family, which includes other bromodomain-containing proteins and their homologues in other species. BRD4 is a protein which functions in both gene activation and repression in cell cycle control and DNA replication. BRD4 functions by binding to the acetylated tails and then attaching to other proteins, allowing those proteins to either activate or repress the histones next to BRD4.BRD4 aids in early cell development by activating pluripotent genes through interacting with Oct4 and recruiting P-TEFb (positive transcription elongation factor). By occupying pluripotent genes and X-chromosome inactivation lncRNAs in their regulatory regions, BRD4 enhances activation of these DNA regions. BRD4 enhances this activation by recruiting P-TEFb; if either BRD4 or P-TEFb is not functional, pluripotent gene transcription is blocked, and the cell differentiates into a neuroectodermal cell.BRD4 can act as epigenetic bookmarking throughout the cell cycle, including after transcription, due to its association with P-TEFb, allowing BRD4 to enhance RNAPII.BRD4 also assists in the hyperacetylation of histones in the sperm nucleus. Histone hyperacetylation, the addition of acetyl groups to lysines on the amino tails of histones in an amount much larger than normal, is believed to assist in histone removal from the sperm nucleus.
Epigenetics of human development	Developmental diseases	Examples of diseases caused by epigenetic dysfunction in development include: Beckwith-Wiedemann Syndrome, caused by abnormal methylation in the maternal ICE region, causing Igf2 overexpression. Symptoms include accelerated growth, abnormal growth (hemihyperplasia), abdominal wall defects, macroglossia, hypoglycemia, kidney abnormalities, and large abdominal organs. Russell-Silver Syndrome, caused by abnormal lack of methylation in the paternal ICE region, causing Igf2 repression. Symptoms include low birth weight, failure to thrive, hypoglycemia, distinctive head shape, abnormal growth, clinodactyly, and digestive issues. Prader-Willi Syndrome, caused by missing paternal expression of the region which UBE3A expression inhibits. Symptoms include hypotonia, feeding difficulties, delayed development, poor growth, hyperphagia, obesity, learning disabilities, intellectual impairment, delayed or incomplete puberty, behavioral issues, sleep abnormalities, and distinctive features. Angelman Syndrome, caused by loss of UBE3A expression in the maternal allele. Symptoms include delayed development, intellectual disability, ataxia, speech impairment, epilepsy, microcephaly, hyperactivity, excitable demeanor, scoliosis, and difficulty sleeping. Alpha thalassemia X-linked syndrome, which can be caused by hypomethylation in certain repeat sequences. Symptoms include delayed development, hypotonia, distinctive facial features, and reduced hemoglobin production. ICF syndrome, caused by a mutation in the DNA methyltransferase 3b gene or DNA hypomethylation, which causes lack of DNA methylation. Symptoms include intellectual impairment and alpha thalassemia. Cancerous stem cells, caused by misregulation of polycomb proteins that often lead to blocking or activating developmental genes at the wrong time. Tumor suppressor genes may be silenced and undifferentiated cells proliferate an increased rate.
Epigenetics of human development	Developmental diseases	There are many diseases that have been closely linked to Hox gene malfunctions, caused by genetic and epigenetic factors such as sequence mutations, overexpression, underexpression, and others. These diseases often involve missing or extra body parts like extra fingers, missing bones, missing auditory organs, limb deformations, etc. Some Hox gene defects have even been shown to cause early cancers. A full list of which genes cause which diseases can be seen in the reference "Human Hox gene disorders" by Quinonez.
Visual system	Visual system	The visual system comprises the sensory organ (the eye) and parts of the central nervous system (the retina containing photoreceptor cells, the optic nerve, the optic tract and the visual cortex) which gives organisms the sense of sight (the ability to detect and process visible light) as well as enabling the formation of several non-image photo response functions. It detects and interprets information from the optical spectrum perceptible to that species to "build a representation" of the surrounding environment. The visual system carries out a number of complex tasks, including the reception of light and the formation of monocular neural representations, colour vision, the neural mechanisms underlying stereopsis and assessment of distances to and between objects, the identification of a particular object of interest, motion perception, the analysis and integration of visual information, pattern recognition, accurate motor coordination under visual guidance, and more. The neuropsychological side of visual information processing is known as visual perception, an abnormality of which is called visual impairment, and a complete absence of which is called blindness. Non-image forming visual functions, independent of visual perception, include (among others) the pupillary light reflex and circadian photoentrainment.
Visual system	Visual system	This article mostly describes the visual system of mammals, humans in particular, although other animals have similar visual systems (see bird vision, vision in fish, mollusc eye, and reptile vision).
Visual system	System overview	Mechanical Together, the cornea and lens refract light into a small image and shine it on the retina. The retina transduces this image into electrical pulses using rods and cones. The optic nerve then carries these pulses through the optic canal. Upon reaching the optic chiasm the nerve fibers decussate (left becomes right). The fibers then branch and terminate in three places.
Visual system	System overview	Neural Most of the optic nerve fibers end in the lateral geniculate nucleus (LGN). Before the LGN forwards the pulses to V1 of the visual cortex (primary) it gauges the range of objects and tags every major object with a velocity tag. These tags predict object movement.
Visual system	System overview	The LGN also sends some fibers to V2 and V3.V1 performs edge-detection to understand spatial organization (initially, 40 milliseconds in, focusing on even small spatial and color changes. Then, 100 milliseconds in, upon receiving the translated LGN, V2, and V3 info, also begins focusing on global organization). V1 also creates a bottom-up saliency map to guide attention or gaze shift.V2 both forwards (direct and via pulvinar) pulses to V1 and receives them. Pulvinar is responsible for saccade and visual attention. V2 serves much the same function as V1, however, it also handles illusory contours, determining depth by comparing left and right pulses (2D images), and foreground distinguishment. V2 connects to V1 - V5.
Visual system	System overview	V3 helps process 'global motion' (direction and speed) of objects. V3 connects to V1 (weak), V2, and the inferior temporal cortex.V4 recognizes simple shapes, and gets input from V1 (strong), V2, V3, LGN, and pulvinar. V5's outputs include V4 and its surrounding area, and eye-movement motor cortices (frontal eye-field and lateral intraparietal area).
Visual system	System overview	V5's functionality is similar to that of the other V's, however, it integrates local object motion into global motion on a complex level. V6 works in conjunction with V5 on motion analysis. V5 analyzes self-motion, whereas V6 analyzes motion of objects relative to the background. V6's primary input is V1, with V5 additions. V6 houses the topographical map for vision. V6 outputs to the region directly around it (V6A). V6A has direct connections to arm-moving cortices, including the premotor cortex.The inferior temporal gyrus recognizes complex shapes, objects, and faces or, in conjunction with the hippocampus, creates new memories. The pretectal area is seven unique nuclei. Anterior, posterior and medial pretectal nuclei inhibit pain (indirectly), aid in REM, and aid the accommodation reflex, respectively. The Edinger-Westphal nucleus moderates pupil dilation and aids (since it provides parasympathetic fibers) in convergence of the eyes and lens adjustment. Nuclei of the optic tract are involved in smooth pursuit eye movement and the accommodation reflex, as well as REM.
Visual system	System overview	The suprachiasmatic nucleus is the region of the hypothalamus that halts production of melatonin (indirectly) at first light.
Visual system	Functions	Visual categorization A major function of the visual system is to categorize visual objects. It has been shown that humans can per perform categorization in briefly presented images in a fraction of a second. These experiments consisted in asking subjects to categorize images that do or do not contain animals. The results showed that humans were able to perform this task very well (with a success rate of more than 95%) but above all that a differential activity for the two categories of images could be observed by electroencephalography, showing that this differentiation emerges with a very short latency in neural activity. These results have been extended to several species, including primates. Different experimental protocols have shown for example that the motor response could be extremely fast (of the order of 120 ms) when the task was to perform a saccade. This speed of the visual cortex in primates is compatible with the latencies that are recorded at the neuro-physiological level. The rapid propagation of the visual information in the thalamus, then in the primary visual cortex takes about 45 ms in the macaque and about 60 ms in humans. This functioning of visual processing as a forward pass is most prominent in fast processing, and can be complemented with feedback loops from the higher areas to the sensory areas.
Visual system	Structure	The eye, especially the retina The optic nerve The optic chiasma The optic tract The lateral geniculate body The optic radiation The visual cortex The visual association cortex.These are components of the visual pathway also called the optic pathway that can be divided into anterior and posterior visual pathways. The anterior visual pathway refers to structures involved in vision before the lateral geniculate nucleus. The posterior visual pathway refers to structures after this point.
Visual system	Structure	Eye Light entering the eye is refracted as it passes through the cornea. It then passes through the pupil (controlled by the iris) and is further refracted by the lens. The cornea and lens act together as a compound lens to project an inverted image onto the retina.
Visual system	Structure	Retina The retina consists of many photoreceptor cells which contain particular protein molecules called opsins. In humans, two types of opsins are involved in conscious vision: rod opsins and cone opsins. (A third type, melanopsin in some retinal ganglion cells (RGC), part of the body clock mechanism, is probably not involved in conscious vision, as these RGC do not project to the lateral geniculate nucleus but to the pretectal olivary nucleus.) An opsin absorbs a photon (a particle of light) and transmits a signal to the cell through a signal transduction pathway, resulting in hyper-polarization of the photoreceptor.
Visual system	Structure	Rods and cones differ in function. Rods are found primarily in the periphery of the retina and are used to see at low levels of light. Each human eye contains 120 million rods. Cones are found primarily in the center (or fovea) of the retina. There are three types of cones that differ in the wavelengths of light they absorb; they are usually called short or blue, middle or green, and long or red. Cones mediate day vision and can distinguish color and other features of the visual world at medium and high light levels. Cones are larger and much less numerous than rods (there are 6-7 million of them in each human eye).In the retina, the photoreceptors synapse directly onto bipolar cells, which in turn synapse onto ganglion cells of the outermost layer, which then conduct action potentials to the brain. A significant amount of visual processing arises from the patterns of communication between neurons in the retina. About 130 million photo-receptors absorb light, yet roughly 1.2 million axons of ganglion cells transmit information from the retina to the brain. The processing in the retina includes the formation of center-surround receptive fields of bipolar and ganglion cells in the retina, as well as convergence and divergence from photoreceptor to bipolar cell. In addition, other neurons in the retina, particularly horizontal and amacrine cells, transmit information laterally (from a neuron in one layer to an adjacent neuron in the same layer), resulting in more complex receptive fields that can be either indifferent to color and sensitive to motion or sensitive to color and indifferent to motion.
Visual system	Structure	Mechanism of generating visual signals The retina adapts to change in light through the use of the rods. In the dark, the chromophore retinal has a bent shape called cis-retinal (referring to a cis conformation in one of the double bonds). When light interacts with the retinal, it changes conformation to a straight form called trans-retinal and breaks away from the opsin. This is called bleaching because the purified rhodopsin changes from violet to colorless in the light. At baseline in the dark, the rhodopsin absorbs no light and releases glutamate, which inhibits the bipolar cell. This inhibits the release of neurotransmitters from the bipolar cells to the ganglion cell. When there is light present, glutamate secretion ceases, thus no longer inhibiting the bipolar cell from releasing neurotransmitters to the ganglion cell and therefore an image can be detected.The final result of all this processing is five different populations of ganglion cells that send visual (image-forming and non-image-forming) information to the brain: M cells, with large center-surround receptive fields that are sensitive to depth, indifferent to color, and rapidly adapt to a stimulus; P cells, with smaller center-surround receptive fields that are sensitive to color and shape; K cells, with very large center-only receptive fields that are sensitive to color and indifferent to shape or depth; another population that is intrinsically photosensitive; and a final population that is used for eye movements.A 2006 University of Pennsylvania study calculated the approximate bandwidth of human retinas to be about 8960 kilobits per second, whereas guinea pig retinas transfer at about 875 kilobits.In 2007 Zaidi and co-researchers on both sides of the Atlantic studying patients without rods and cones, discovered that the novel photoreceptive ganglion cell in humans also has a role in conscious and unconscious visual perception. The peak spectral sensitivity was 481 nm. This shows that there are two pathways for sight in the retina – one based on classic photoreceptors (rods and cones) and the other, newly discovered, based on photo-receptive ganglion cells which act as rudimentary visual brightness detectors.
Visual system	Structure	Photochemistry The functioning of a camera is often compared with the workings of the eye, mostly since both focus light from external objects in the field of view onto a light-sensitive medium. In the case of the camera, this medium is film or an electronic sensor; in the case of the eye, it is an array of visual receptors. With this simple geometrical similarity, based on the laws of optics, the eye functions as a transducer, as does a CCD camera.
Visual system	Structure	In the visual system, retinal, technically called retinene1 or "retinaldehyde", is a light-sensitive molecule found in the rods and cones of the retina. Retinal is the fundamental structure involved in the transduction of light into visual signals, i.e. nerve impulses in the ocular system of the central nervous system. In the presence of light, the retinal molecule changes configuration and as a result, a nerve impulse is generated.
Visual system	Structure	Optic nerve The information about the image via the eye is transmitted to the brain along the optic nerve. Different populations of ganglion cells in the retina send information to the brain through the optic nerve. About 90% of the axons in the optic nerve go to the lateral geniculate nucleus in the thalamus. These axons originate from the M, P, and K ganglion cells in the retina, see above. This parallel processing is important for reconstructing the visual world; each type of information will go through a different route to perception. Another population sends information to the superior colliculus in the midbrain, which assists in controlling eye movements (saccades) as well as other motor responses.
Visual system	Structure	A final population of photosensitive ganglion cells, containing melanopsin for photosensitivity, sends information via the retinohypothalamic tract to the pretectum (pupillary reflex), to several structures involved in the control of circadian rhythms and sleep such as the suprachiasmatic nucleus (the biological clock), and to the ventrolateral preoptic nucleus (a region involved in sleep regulation). A recently discovered role for photoreceptive ganglion cells is that they mediate conscious and unconscious vision – acting as rudimentary visual brightness detectors as shown in rodless coneless eyes.

Subsets and Splits

No community queries yet

The top public SQL queries from the community will appear here once available.