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Speedrunning

Speedrunning is the act of playing a video game, or section of a video game, with the goal of completing it as fast as possible. Speedrunning often involves following planned routes, which may incorporate sequence breaking and exploit glitches that allow sections to be skipped or completed more quickly than intended. Tool-assisted speedrunning (TAS) is a subcategory of speedrunning that uses emulation software or additional tools to create a precisely controlled sequence of inputs.

Many online communities revolve around speedrunning specific games; community leaderboard rankings for individual games form the primary competitive metric for speedrunning. Racing between two or more speedrunners is also a popular form of competition. Videos and livestreams of speedruns are shared via the internet on media sites such as YouTube and Twitch. Speedruns are sometimes showcased at marathon events, which are gaming conventions that feature multiple people performing speedruns in a variety of games.

Early examples
Speedrunning has been generally an intrinsic part of video games since the early days of the medium, similar to the chasing of high scores, though it did not achieve broad interest until 1993. According to Sacha Bernard, it would appear that the term 'speedrun', understood as ' speed-based videogame performance ', originated with the game Radar Rat Race published in 1981 by HAL Laboratory. Some groundwork for what would become speedrunning was established by id Software during the development for Wolfenstein 3D (1992). The game recorded a "par time" statistic which was based on John Romero's personal records for each level. Romero's best level times were also printed in the official hint book, which was available via the same mail order system used to distribute the game at the time. His intention was that players would attempt to beat his times.

Doom and Quake demos, early Internet communities
The development of a speedrunning community is considered to have originated with the 1993 computer game Doom. The game retained the "par time" mechanic from Wolfenstein and included a feature that allowed players to record and play back gameplay using files called demos (also known as game replays). Demos were lightweight files that could be shared more easily than video files on Internet bulletin board systems at the time. Internally, In January 1994, University of Waterloo student Christina Norman created a File Transfer Protocol server dedicated to compiling demos, named the LMP Hall of Fame (after the .lmp file extension used by Doom demos). The LMP Hall of Fame inspired the creation of the Doom Honorific Titles by Frank Stajano, a catalogue of titles that a player could obtain by beating certain challenges in the game. The Doom speedrunning community emerged in November 1994, when Simon Widlake created COMPET-N, a website hosting leaderboards dedicated to ranking completion times of Doom 's single-player levels.

In 1996, id Software released Quake as a successor to the Doom series. Like its predecessor, Quake had a demo recording feature and drew attention from speedrunners. In April 1997, Nolan "Radix" Pflug created Nightmare Speed Demos (NSD), a website for tracking Quake speedruns. In June 1997, Pflug released a full-game speedrun demo of Quake called Quake done Quick, which introduced speedrunning to a broader audience. Quake speedruns were notable for their breadth of movement techniques, including "bunny hopping," a method of gaining speed also present in future shooting games like Counter-Strike and Team Fortress. In April 1998, NSD merged with another demo-hosting website to create Speed Demos Archive.

Speed Demos Archive and video sharing
For five years, Speed Demos Archive hosted exclusively Quake speedruns, but in 2003 it published a 100% speedrun of Metroid Prime done by Pflug. Six months later, SDA began accepting runs from all games. Unlike its predecessor websites, SDA did not compile leaderboards for their games; they displayed only the fastest speedrun of each game. Until SDA's expansion into games other than Quake in 2004, speedrun video submissions were primarily sent to early video game record-keeper Twin Galaxies. The videos were often never publicly released, creating verifiability concerns that SDA aimed to address. It was often impossible to determine what strategies had gone into setting these records, hindering the development of speedrunning techniques. Sites dedicated to speedrunning, including game-specific sites, began to establish the subculture around speedrunning. These sites were not only used for sharing runs but also to collaborate and share tips to improve times, leading to collaborative efforts to continuously improve speedrunning records on certain games.

In 2003, a video demonstrating a TAS of Super Mario Bros. 3 garnered widespread attention on the internet; many speedrunners cite this as their first introduction to the hobby. It was performed and published by a Japanese user named Morimoto. The video was lacking context to indicate that it was a TAS, so many people believed it to be an actual human performance. It drew criticism from viewers who felt "cheated" when Morimoto later explained the process by which he created the video and apologized for the confusion. In December 2003, after seeing Morimoto’s TAS, a user named Bisqwit created TASVideos (initially named NESVideos ), a site dedicated to displaying tool-assisted speedruns.

The creation of video-sharing and streaming websites in the late 2000s and early 2010s contributed to an increase in the accessibility and popularity of speedrunning. In 2005, the creation of YouTube enabled speedrunners to upload and share videos of speedruns and discuss strategies on the SDA forums. Twitch, a livestreaming website centered around video gaming, was launched in 2011. The advent of livestreaming made for easier verification and preservation of speedruns, and some speedrunners believe it is responsible for a shift towards collaboration among members of the community. In 2014, Speedrun.com was created, which had less stringent submission guidelines than SDA and was intended to centralize speedrun leaderboards for many different games. Speedrunners' move towards using Speedrun.com and social media platforms like Skype and Discord contributed to SDA's relevance waning in the 2010s.

Gameplay strategies
Routing is a fundamental process in speedrunning. Routing is the act of developing an optimal sequence of actions and stages in a video game. A route may involve skipping one or more important items or sections. Skipping a part of a video game that is normally required for progression is referred to as sequence breaking, a term first used in reference to the 2002 action-adventure game Metroid Prime. Video game glitches may be used to achieve sequence breaks, or may be used for other purposes such as skipping cutscenes and increasing the player's speed or damage output. Some people, called glitch-hunters, choose to focus on finding glitches that will be useful to speedrunners. In some games, arbitrary code execution exploits may be possible, allowing players to write their own code into the game's memory. Several speedruns use a "credits warp", a category of glitch that causes the game's credits sequence to play, which may require arbitrary code execution. The use of glitches and sequence breaks in speedruns was historically not allowed, per the rules of Twin Galaxies' early leaderboards. When speedrunning moved away from Twin Galaxies towards independent online leaderboards, their use became increasingly common.

Tool-assisted speedruns
A tool-assisted speedrun (TAS) is a speedrun that uses emulation software and tools to create a "theoretically perfect playthrough". According to TASVideos, common examples of tools include advancing the game frame by frame to play the game more precisely, retrying parts of the run using savestates, and hex editing. These tools are designed to remove restrictions imposed by human reflexes and allow for optimal gameplay. The run is recorded as a series of controller inputs intended to be fed back to the game in sequence. Although generally recorded on an emulator, TASes can be played back on original console hardware by sending inputs into the console's controller ports, a process known as console verification (as some exploits are possible on emulation but not console). To differentiate them from tool-assisted speedruns, unassisted speedruns are sometimes referred to as real-time attack (RTA) speedruns. Due to the lack of a human playing the game in real time, TASes are not considered to be in competition with RTA speedruns.

Categorization and ranking
Speedruns are divided into various categories that impose additional limitations on a runner. It is common for category restrictions to require a certain amount of content to be completed in the game. Each video game may have its own speedrun categories, but some categories are popular irrespective of game. The most common are:

Speedrunners compete in these categories by ranking times on online leaderboards. According to Wired, the definitive website for speedrun leaderboards is Speedrun.com. the site hosts leaderboards for over 20,000 video games. Runners usually record footage of their speedruns for accurate timing and verification, and may include a timer in their videos. They often use timers that keep track of splits—the time between the start of the run and the completion of some section or objective. Verification is usually done by leaderboard moderators who review submissions and determine the validity of individual speedruns.
 * Any%, which involves getting to the end as fast as possible with no qualifier,
 * 100%, which requires full completion of a game. This may entail obtaining all items or may use some other metric.
 * Low%, the opposite of 100%, which requires the player to beat the game while completing the minimum amount possible.
 * Glitchless, which restricts the player from performing any glitches during the speedrun.
 * No Major Glitches, Which consist of beating the game as fast as possible while not using any "game breaking" glitches.

Community
According to many speedrunners, community is an important aspect of the hobby. Matt Merkle, director of operations at Games Done Quick, says that speedrunners "value the cooperation the community encourages," and many speedrunners have said that their mental health has improved because of their involvement in the community. Erica Lenti, writing for Wired, said a sense of community is vital to speedrunning because it motivates players and aids in the development of routes and tricks used in speedruns, and Milan Jacevic highlighted "years of research" and collective community efforts that contribute to world records.

Speedrunners use media-sharing sites like YouTube and Twitch to share videos and livestreams of speedruns. The speedrunning community is divided into many sub-communities focused on speedrunning specific games. These sub-communities can form their own independent leaderboards and communicate about their games using Discord. Many communities have used the centralized leaderboard hosting site Speedrun.com since its founding in 2014.

Marathons
Speedrunning marathons, a form of gaming convention, feature a series of speedruns by multiple speedrunners. While many marathons are held worldwide, the largest event is Games Done Quick, a semiannual marathon held in the United States. it has raised over $37 million for charity organizations since its inception in 2010. The largest marathon in Europe is the European Speedrunner Assembly, held in Sweden. Both events broadcast the speedruns on Twitch and raise money for various charity organizations. Speedruns at marathons are done in one attempt and often have accompanying commentary. Many people consider marathons to be important to runners and spectators in the speedrunning community. Peter Marsh, writing for the Australian Broadcasting Corporation, says that the Games Done Quick events provide an inclusive space for women and the LGBTQ community in contrast to the related cultures of gaming and Twitch streaming. Alex Miller of Wired says the events have played an important role in connecting people and supporting international humanitarian organization Médecins Sans Frontières during the COVID-19 pandemic.

Speedrun races
Races between two or more speedrunners are a common competition format. They require players to be skilled at recovering from setbacks during a speedrun because they cannot start over. Occasionally, races are featured at marathons; a 4-person Super Metroid race is a popular recurring event at Games Done Quick marathons. The Global Speedrun Association (GSA) have organized head-to-head tournaments for multiple games, including Celeste, Super Mario 64, and Super Mario Odyssey. In 2019, GSA organized an in-person speedrun race event called PACE. Their efforts have drawn criticism from some speedrunners who believe that they "undermine the community spirit", citing cash prizes as incentives to avoid collaboration with other speedrunners and ignore games without prize money. Video game randomizers—ROM hacks that randomly shuffle item locations and other in-game content—are popular for speedrun races as well. Tournaments and other events have been organized for randomizer races, and they have been featured at speedrun marathons.

Methods
Similar to other competitions, there are several methods that players use to try to gain an unfair advantage in speedrunning:

Splicing
Splicing is by far the most popular cheating method in speedrunning. Here, a speedrun is not recorded continuously, as is usually the case, but instead composed of various video snippets recorded at different times, sometimes with gameplay stolen from TAS composers or legitimate players.

At SGDQ 2019, speedrunner "ConnorAce" used a spliced run to illegitimately claim the world record on Clustertruck for the "NoAbility%" category, depriving the legitimate record holder from being invited to the event. The run was treated with suspicion due to it not being submitted officially to speedrun.com, with the video being unlisted on YouTube prior to ConnorAce's acceptance into SGDQ. In October 2019, ConnorAce's run was exposed by the YouTube documentarian Apollo Legend.

In a typical case, splicing allows difficult segments to be repeated to perfection and edited together afterwards into one seemingly continuous effort, which can sometimes dramatically reduce the amount of time needed to grind out a comparable score. However, a spliced run is not considered cheating if it is announced to be a multi-segment run upon submission; for example, this community-made multi-segment compilation for Super Mario Bros.

TASbotting
When 'TASbotting', the player records their controller inputs as a tool-assisted run in an external device in order to then have this device reproduce the inputs on a real console. As with splicing, the inputs of individual segments can be combined and, as is usual for tool-assisted runs, inputs can be made frame by frame. As long as these inputs are authentic and seem realistic for a human being, such manipulations are much more difficult to detect in the resulting video product than splicing. If, on the other hand, a TAS is not outputted on the original hardware but, as usual, on emulators, it can sometimes be alleged from the resulting video that such auxiliary programs were used; additionally, some emulators never perfectly imitate the desired hardware, which can cause synchronization issues when replayed on a console.

Modifying the timer or playback speed
Modifying game timers, especially on computer games, is another common method to improve one's recorded times. However, this is a very noticeable manipulation, especially in highly competitive areas, since the speedruns in the upper area of leaderboards are repeatedly analyzed by other players in order to check their legitimacy and playback reproducibility, including a temporal check known as "retiming". This often reveals discrepancies between one's recording time and a speedrun in the leaderboards. Another method, a variation of splicing, includes speeding up cutscenes or compressing transitional black space. Again, such methods are likely to be detected by a speedrun moderator, although some games, especially where PC speed can have an effect, may actually vary depending on hardware. Finally, another common cheating method is to play the game using frame-by-frame advancement or in slow motion, which is similar to normal tool-assisted speedrunning but without the ability to redo inputs. Playing in slow motion is often effective for games that require very precise movements.

Modifying in-game files
While it is often possible to use traditional cheats such as a GameShark to increase character speed, strength, health, etc., such cheats are generally quite easy for an experienced moderator to detect, even when applied subtly. However, the modification of internal files to improve RNG can often be much more difficult to detect. One of the most infamous examples of file modification was several cheated runs by the speedrunner Dream in 2020, whose luck was considered so extreme in a series of Minecraft speedruns that they were considered exceedingly unlikely to have been done without cheating (with an approximately 1 in 20 sextillion chance of occurring, as estimated by Matt Parker from Numberphile) by both the moderators at Speedrun.com and various YouTubers, such as Karl Jobst and Matt Parker, whose videos on Dream gained a combined 5.7 million and 6.5 million views, respectively, as of January 2024. Dream later admitted to the runs being cheated about five months after his runs were rejected, although he claimed he did not know he was using a modified version of the game. Nearly two years later, the player who helped uncover Dream's cheated runs, MinecrAvenger, was also found to be using similar luck manipulation in late 2022.

Lying about times
While all of the aforementioned methods are deceptive in nature, the simplest way of cheating is merely to lie about a time. One of the most infamous cases of this was done by Todd Rogers. Several of his records have come under scrutiny for being seemingly impossible or lacking sufficient proof. In 2002, Robert Mruczek, then chief referee at Twin Galaxies, officially rescinded Todd's record time in Barnstorming after other players pointed out that his time of 32.04 seconds did not appear to be possible, even when the game was hacked to remove all obstacles. Upon further investigation, Twin Galaxies referees were unable to find independent verification for this time, having instead been relying on erroneous information from Activision.

As listed on the Twin Galaxies leaderboard until January 2018, Rogers's record in the 1980 Activision game Dragster was a time of 5.51 seconds from 1982. At the time, Activision verified high scores by Polaroid. According to Rogers, after he submitted a photo of this time, he was called by Activision, who asked him to verify how he achieved such a score, because they had programmed a 'perfect run' of the game and were unable to achieve better than a 5.54. The game's programmer David Crane would later confirm that he had a vague recollection of programming test runs, but did not remember the results. In 2012, Todd received a Guinness World Record for the longest-standing video game score record, for his 1982 Dragster record. In 2017, a speedrunner named Eric "Omnigamer" Koziel disassembled the game's code and concluded that the fastest possible time was 5.57 seconds. With a tick rate of 0.03 seconds, the record claim is two ticks faster than Omnigamer's data and one tick faster than the reported Activision 'perfect run'.

Cheat detection
In order to prevent most of these methods, some games require a video of the hands on the controller or keyboard ("handcam"), in addition to the screen recording, so that game-specific moderators in charge of authenticating a submission can ensure that the inputs are really done in the specified combination and by a human. Other methods include forensic audio analysis, which is a common method for detecting telltale signs of video splicing; this is why runs without high-quality audio streams are often rejected on speedrun boards.

Additional detection methods are the use of mathematics (as in the aforementioned Dream case) or human moderation of suspicious inputs (in games which record them such as Doom and TrackMania). Cheat detection software created for TrackMania was used to analyze over 400,000 replays and isolate a handful of cheaters, leading to hundreds of world records being determined to have been cheated using slowdown tools. This included those of Burim "riolu" Fejza, who was signed to the eSports team Nordavind (now known as 00 Nation) before being dropped following the scandal.

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Talk:Newfane, New York

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Ok, this one is my fault. I overlooked the possibility of "Newfane (town), New York. I put the guts of this into that article so this one needs to GO AWAY. Tmesmpt 3.3.04.
 * Actually, this one should have been kept. The other one should have gone, since there is no other Newfane (so the "town" descriptor is unnecessary).  I'm going to do an unpopular cut-and-paste move, since I cannot move it the normal way since this page exists. Oz Lawyer  15:07, 4 August 2006 (UTC)

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: Talk:Newfane, New York


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IX Corps

9 Corps, 9th Corps, Ninth Corps, or IX Corps may refer to:

France

 * 9th Army Corps (France)
 * IX Corps (Grande Armée), a unit of the Imperial French Army during the Napoleonic Wars

Germany

 * IX Corps (German Empire), a unit of the Imperial German Army prior to and during World War I
 * IX Reserve Corps (German Empire), a unit of the Imperial German Army during World War
 * IX Army Corps (Wehrmacht), a unit in World War II
 * IX SS Mountain Corps, a unit in World War II

Other countries

 * IX Corps (India)
 * IX Corps (Ottoman Empire)
 * IX Corps (United Kingdom)
 * IX Corps (Union Army)
 * IX Corps (United States)
 * 9th Corps (Yugoslav Partisans)

title: IX Corps


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List of cities in Mauritania

This is a list of cities in Mauritania by population. All settlements with a population over 10,000 are listed.

Other settlements

 * Akreijit (أكريجيت)
 * Bir Moghrein (بير مغرين)
 * Chinguetti (شنقيط)
 * Choum (شوم)
 * F'dérik (افديرك)
 * Ouadane (وادان)
 * Tichit (تيشيت)

title: List of cities in Mauritania


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Template:Cellular structures

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title: Template:Cellular structures


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Gary Graham

Gary Rand Graham (June 6, 1950 – January 22, 2024) was an American actor. With a career spanning five decades beginning in the 1970s in television and movies, he is perhaps best known for his starring role as Detective Matthew Sikes in the television series Alien Nation (1989–1990) and five subsequent Alien Nation television films (1994–1997), as well as his work in the Star Trek franchise, most notably the recurring role of Soval, the Vulcan ambassador to Earth in Star Trek: Enterprise.

Biography and early career
Graham was born in Long Beach, California. One of his earliest roles was in the 1980 CBS mini series Scruples based on the Judith Krantz novel starring Lindsay Wagner. He was cast as a "hitman" on the television show Moonlighting co-starring opposite Bruce Willis. Graham played more than 38 TV roles and had been in more than 40 movies.

As a musician, Graham was in the bands The Gary Graham Garage Band, The Gary Graham Band and The Sons of Kirk.

Graham was also a contributor to Breitbart News.

Graham died from cardiac arrest in Spokane, Washington on January 22, 2024, at the age of 73.

Television
Graham starred in a 2008 television pilot styled after Sin City called Dead End City. He also appeared in the December 18, 1984 episode of Remington Steele, "Let's Steele A Plot" (season 3, episode 11), as Butch Beemis.

As well as starring as Detective Matthew Sikes in the television series Alien Nation (1989–1990), he resumed this role in the TV movies Alien Nation: Dark Horizon (1994), Alien Nation: Body and Soul (1995), Alien Nation: Millennium (1996), Alien Nation: The Enemy Within (1996), and Alien Nation: The Udara Legacy (1997).

Graham starred on Star Trek: Enterprise as the recurring character Ambassador Soval, a Vulcan ambassador to Earth. He also guest-starred on Star Trek: Voyager (1995) once, playing Ocampan community leader Tanis in the season 2 episode "Cold Fire". He played Ragnar in the fan production Star Trek: Of Gods and Men and continued that role in Star Trek: Renegades.

In 2015, Graham reprised his role as Ambassador Soval, in the fan film Star Trek: Axanar.

Film
Graham's film appearances include Hardcore, The Hollywood Knights, All the Right Moves, The Arrogant, The Last Warrior, Robot Jox, Running Woman and Siren. His most recent films are InAlienable, Action Hero and Dreams Awake. He made his directorial debut in the spring of 2008 with the film Interviews, which he also wrote.

Web-based work
Graham also made appearances as the "Smoking Jacket Guy" in the introduction and other scenes in the Internet gaming show The Jace Hall Show. Graham played Dr. David Macavoy in the web series Universal Dead. In late June 2010, it was announced that Universal Dead will be made into a feature film.

title: Gary Graham


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Clathrin

Clathrin is a protein that plays a major role in the formation of coated vesicles. Clathrin was first isolated by Barbara Pearse in 1976. It forms a triskelion shape composed of three clathrin heavy chains and three light chains. When the triskelia interact they form a polyhedral lattice that surrounds the vesicle. The protein's name refers to this lattice structure, deriving from Latin clathri meaning lattice. Barbara Pearse named the protein clathrin at the suggestion of Graeme Mitchison, selecting it from three possible options. Coat-proteins, like clathrin, are used to build small vesicles in order to transport molecules within cells. The endocytosis and exocytosis of vesicles allows cells to communicate, to transfer nutrients, to import signaling receptors, to mediate an immune response after sampling the extracellular world, and to clean up the cell debris left by tissue inflammation. The endocytic pathway can be hijacked by viruses and other pathogens in order to gain entry to the cell during infection.

Structure
The clathrin triskelion is composed of three clathrin heavy chains interacting at their C-termini, each ~190 kDa heavy chain has a ~25 kDa light chain tightly bound to it. The three heavy chains provide the structural backbone of the clathrin lattice, and the three light chains are thought to regulate the formation and disassembly of a clathrin lattice. There are two forms of clathrin light chains, designated a and b. The main clathrin heavy chain, located on chromosome 17 in humans, is found in all cells. A second clathrin heavy chain gene, on chromosome 22, is expressed in muscle.

Clathrin heavy chain is often described as a leg, with subdomains, representing the foot (the N-terminal domain), followed by the ankle, distal leg, knee, proximal leg, and trimerization domains. The N-terminal domain consists of a seven-bladed β-propeller structure. The other domains form a super-helix of short alpha helices. This was originally determined from the structure of the proximal leg domain that identified and is composed of a smaller structural module referred to as clathrin heavy chain repeat motifs. The light chains bind primarily to the proximal leg portion of the heavy chain with some interaction near the trimerization domain. The β-propeller at the 'foot' of clathrin contains multiple binding sites for interaction with other proteins.

When triskelia assemble together in solution, they can interact with enough flexibility to form 6-sided rings (hexagons) that yield a flat lattice, or 5-sided rings (pentagons) that are necessary for curved lattice formation. When many triskelions connect, they can form a basket-like structure. The structure shown, is built of 36 triskelia, one of which is shown in blue. Another common assembly is a truncated icosahedron. To enclose a vesicle, exactly 12 pentagons must be present in the lattice.

In a cell, clathrin triskelion in the cytoplasm binds to an adaptor protein that has bound membrane, linking one of its three feet to the membrane at a time. Clathrin cannot bind to membrane or cargo directly and instead uses adaptor proteins to do this. This triskelion will bind to other membrane-attached triskelia to form a rounded lattice of hexagons and pentagons, reminiscent of the panels on a soccer ball, that pulls the membrane into a bud. By constructing different combinations of 5-sided and 6-sided rings, vesicles of different sizes may assemble. The smallest clathrin cage commonly imaged, called a mini-coat, has 12 pentagons and only two hexagons. Even smaller cages with zero hexagons probably do not form from the native protein, because the feet of the triskelia are too bulky.

Function
Clathrin performs critical roles in shaping rounded vesicles in the cytoplasm for intracellular trafficking. Clathrin-coated vesicles (CCVs) selectively sort cargo at the cell membrane, trans-Golgi network, and endosomal compartments for multiple membrane traffic pathways. After a vesicle buds into the cytoplasm, the coat rapidly disassembles, allowing the clathrin to recycle while the vesicle gets transported to a variety of locations.

Adaptor molecules are responsible for self-assembly and recruitment. Two examples of adaptor proteins are AP180 and epsin. AP180 is used in synaptic vesicle formation. It recruits clathrin to membranes and also promotes its polymerization. Epsin also recruits clathrin to membranes and promotes its polymerization, and can help deform the membrane, and thus clathrin-coated vesicles can bud. In a cell, a triskelion floating in the cytoplasm binds to an adaptor protein, linking one of its feet to the membrane at a time. The triskelion foot will bind to other ones attached to the membrane to form a polyhedral lattice, triskelion foot, which pulls the membrane into a bud. The foot does not bind directly to the membrane, but binds to the adaptor proteins that recognize the molecules on the membrane surface.

Clathrin has another function aside from the coating of organelles. In non-dividing cells, the formation of clathrin-coated vesicles occurs continuously. Formation of clathrin-coated vesicles is shut down in cells undergoing mitosis. During mitosis, clathrin binds to the spindle apparatus, in complex with two other proteins: TACC3 and ch-TOG/CKAP5. Clathrin aids in the congression of chromosomes by stabilizing kinetochore fibers of the mitotic spindle. The amino-terminal domain of the clathrin heavy chain and the TACC domain of TACC3 make the microtubule binding surface for TACC3/ch-TOG/clathrin to bind to the mitotic spindle. The stabilization of kinetochore fibers requires the trimeric structure of clathrin in order to crosslink microtubules.

Clathrin-mediated endocytosis (CME) regulates many cellular physiological processes such as the internalization of growth factors and receptors, entry of pathogens, and synaptic transmission. It is believed that cellular invaders use the nutrient pathway to gain access to a cell's replicating mechanisms. Certain signalling molecules open the nutrients pathway. Two chemical compounds called Pitstop 1 and Pitstop 2, selective clathrin inhibitors, can interfere with the pathogenic activity, and thus protect the cells against invasion. These two compounds selectively block the endocytic ligand association with the clathrin terminal domain in vitro. However, the specificity of these compounds to block clathrin-mediated endocytosis has been questioned. In later studies, however, the specificity of Pitstop 2 was validated as being clathrin dependent.

title: Clathrin


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Hieronymus

Hieronymus, in English pronounced or, is the Latin form of the Ancient Greek name Ἱερώνυμος (Hierṓnymos), meaning "with a sacred name". It corresponds to the English given name Jerome.

Variants

 * Albanian: Jeronimi
 * Arabic: جيروم (Jerome)
 * Basque: Jeronimo
 * Belarusian: Еранім (Yeranim)
 * Bulgarian: Йероним (Yeronim)
 * Catalan: Jeroni
 * Written Chinese: 希罗尼穆斯
 * Chinese Pinyin: xī luó ní mù sī
 * Croatian: Jeronim
 * Czech: Jeroným, Jeronýmus (archaic)
 * Danish: Hieronymus
 * Dutch: Hiëronymus, Jeroen
 * English: Jerome, Hieronymus, Geromy, Rhonemus, Geronimo
 * Esperanto: Hieronimo
 * Estonian: Hieronymus
 * Finnish: Hieronymus
 * Flemish: Jerom
 * French: Jérôme, Gérôme
 * Galician Xerome
 * German: Hieronymus
 * Ancient Greek : Ἱερώνυμος (Hierṓnymos)
 * Modern Greek: Ιερώνυμος (Ierónymos)
 * Hebrew: הירונימוס (Hieronymus)
 * Hungarian: Jeromos
 * Indonesian: Hieronimus
 * Interlingua: Jeronimo
 * Italian: Girolamo, Gerolamo, Geronimo, Geromino
 * Japanese: ヒエロニムス (Hieronimusu)
 * Korean: 히에로니무스 (Hieronimuseu), 제롬 (Jerom)
 * Latin: Hieronymus
 * Lithuanian: Jeronimas
 * Malayalam: ജെറോം
 * Norwegian: Hieronymus
 * Polish: Hieronim
 * Portuguese: Jerónimo, Brazilian Jerônimo, or Jeronymo as an Azorian family name
 * Romanian: Ieronim
 * Russian: Иероним (Iyeronim)
 * Sardinian: Ziròminu
 * Dutch Low Saxon: Hiëronymus
 * Serbian: Јероним (Jeronim)
 * Slovak: Hieronym
 * Spanish: Jerónimo
 * Swahili: Jeromu
 * Swedish: Hieronymus
 * Tagalog: Jeronimo, Geronimo
 * Thai: เจอโรม (Čhoerom), เยโรม (Yoerom; a historical distorted interpretation of the name)
 * Ukrainian: Єронім (Yeronim), Єроним (Yeronym), Ієронім (Iyeronim)
 * Vietnamese: Giêrônimô

As a given name

 * Eusebius Sophronius Hieronymus, better known as Saint Jerome (c. 347 – 420)
 * Hiëronymus Emiliani, better known as St. Jerome Emiliani (1486–1537)
 * Hieronymus of Cardia, Greek general and historian
 * Hieronymus of Rhodes, Greek peripatetic philosopher of the 3rd century BC
 * Hieronymus of Syracuse, Greek tyrant
 * Archbishop Ieronymos II of Athens
 * Hieronymus, son of Charles Martel
 * Hieronymus (bishop of Wrocław), early medieval Bishop of Wrocław, Poland from 1046 to 1062
 * Hieronymus Bock, German botanist
 * Hieronymus Bosch, Dutch artist
 * Hieronymus Cardanus, also known as Girolamo Cardano or Jérôme Cardan, polymath, astrologer, gambler
 * Hieronymus Cock, Flemish painter and etcher
 * Hieronymus Fabricius, Italian anatomist
 * Hieronymus Graf von Colloredo, Austrian Prince-Archbishop of Salzburg, Count of the Holy Roman Empire
 * Hieronymus Karl Friedrich von Münchhausen, famous recounter of tall tales, fictionalized as Baron Munchausen (1720–1797)
 * Hieronymus Praetorius, German Composer
 * Hieronymus Theodor Richter, German chemist
 * Marcus Hieronymus Vida, 16th-century Italian poet and bishop
 * Hieronymus Vietor (c. 1480–1546/47), printer in Vienna and Kraków
 * Hieronymus Wierix, Flemish engraver
 * Hieronymus Wolf, German historian
 * Hieronymus Georg Zeuthen, Danish mathematician
 * Hieronymus, pen name of Athalia Schwartz (1821-1871), Danish writer

As a surname

 * Georg Hans Emmo Wolfgang Hieronymus, German botanist
 * , German engineer
 * Holger Hieronymus, German former football player

Fictional characters

 * Detective Hieronymus "Harry" Bosch, a fictional character
 * Charlie Hieronymus Pace, a character from the television series Lost
 * Hieronymus Bump, a character from the animated fantasy television series The Owl House
 * Hieronymus Frosch, a character (frog and inventor) created by
 * Hieronymus Fox, a character from the science-fiction television series Buck Rogers in the 25th century
 * Hieronymus Glove from the animated American television series SpongeBob SquarePants
 * Hieronymus Lex, a character from the video game The Elder Scrolls IV: Oblivion

title: Hieronymus


text:
List of cities in Malawi

This is a list of towns and cities in Malawi:

Northern Region

 * Chitipa
 * Chilumba
 * Ekwendeni
 * Karonga
 * Likoma
 * Livingstonia
 * Mzimba
 * Mzuzu
 * Nkhata Bay
 * Rumphi
 * Chintheche
 * Embangweni

Central Region

 * Aaron
 * Chipoka
 * Dedza
 * Dowa
 * Kasungu
 * Lilongwe
 * Mchinji
 * Mponela
 * Mua
 * Namitete
 * Madisi
 * Nkhotakota
 * Nkhoma
 * Ntcheu
 * Ntchisi
 * Salima

Southern Region

 * Balaka
 * Bangula
 * Blantyre
 * Chikwawa
 * Chiradzulu
 * Chiwembe
 * Domasi
 * Limbe
 * Liwonde
 * Luchenza
 * Machinga
 * Malosa
 * Mangochi
 * Marka
 * Monkey Bay
 * Mulanje
 * Njata
 * Nkaya
 * Nsanje
 * Phalombe
 * Thyolo
 * Zalewa
 * Zomba

title: List of cities in Malawi


text:
Hermit kingdom

The term hermit kingdom is an epithet used to refer to any country, organization or society that willfully isolate itself off, either metaphorically or physically, from the rest of the world. The Democratic People's Republic of Korea (North Korea) is commonly cited as a prominent example of a hermit kingdom in the present day.

Historic use: Korea
The first country to be described as a "hermit kingdom" was Korea during the Joseon dynasty, in William Elliot Griffis's 1882 book Korea: The Hermit Nation. Korea, which had become increasingly isolationist since the 17th century, was frequently described as a hermit kingdom until 1905, when it became a protectorate of Japan.

Cold War uses
During the Cold War, Enver Hoxha's Albania was widely considered a "hermit kingdom" as it was a Stalinist regime, did not allow ordinary citizens out of the country, and pursued autarky to become entirely self-sufficient. Unlike North Korea, Hoxha's regime, after the Sino-Albanian split, refused to ally with anyone and was hostile towards the entire world, which made it more isolationist than North Korea, which was then Stalinist but was allied with other Eastern Bloc states and did not become isolationist until after the end of the Cold War.

Modern use
Today, the term is often applied to North Korea in news and social media, and in 2009, it was used by Hillary Clinton, then the United States Secretary of State. Other current countries considered isolationist "hermit kingdoms" include Turkmenistan, Belarus,  Eritrea, and the Islamic Emirate of Afghanistan. Historically, the term has been applied to Nepal, Ladakh, and Bhutan in the Himalayas.

Other uses
The term "hermit kingdom" has also been used to describe Western Australia when it closed its borders during the COVID pandemic.

title: Hermit kingdom


text:
List of cities in Niger

This is a list of cities and towns in Niger. All larger cities are also Communes of Niger. While often translated as "town", Nigerien communes are simply the third level administrative subdivision of the nation. These can be classified Urban or Rural communes, and while often the administrative unit of a town or city, all areas of the country fall within a commune. Smaller towns and neighborhoods are designated Quarters (Urban) or Villages (Rural).

Largest cities and urban centers
Cities with population over 10,000 according to 2012 census.

Agadez Region

 * Aderbissinat
 * Agessis
 * Aouderas
 * Aratène
 * Arlit
 * Assamakka
 * Assodé
 * Bilma
 * Dabaga
 * Fachi
 * Iferouane
 * In-Gall
 * Madama
 * Tegguiada In Tessoum
 * Timia
 * Tin Dawin

Diffa Region

 * Goudoumaria
 * Bosso
 * Chétimari
 * N'Gourti
 * Kabléwa
 * N'Guelbély
 * Gueskérou
 * Nguigmi

Dosso Region

 * Dogondoutchi
 * Gaya
 * Koré Maïroua

Maradi Region

 * Galmi
 * Guidan Roumji
 * Mayahi

Tahoua Region

 * Akoubounou
 * Bouza
 * Dabnou
 * Korahane
 * Malbaza Uzine
 * Tchin-Tabaraden
 * Galmi

Tillabéri Region

 * Ayourou
 * Balléyara
 * Bani-Bangou
 * Diagorou
 * Karma
 * Matankari
 * Ouallam
 * Tera
 * Kourteye
 * Koulikoira

Zinder Region

 * Cheri
 * Guidimouni
 * Kelakam
 * Mar-Jirgui
 * Samia
 * Takieta

Niamey Urban Community

 * Gaweye
 * Lamordé
 * Soudouré

title: List of cities in Niger


text:
Electronic voting in India

Electronic voting is the standard means of conducting elections using Electronic Voting Machines (EVMs) in India. The system was developed for the Election Commission of India by state-owned Electronics Corporation of India and Bharat Electronics. Starting in the late 1990s, they were introduced in Indian elections in a phased manner.

Prior to the introduction of electronic voting, paper ballots were used and manual counting was done. The printed paper ballots were expensive, required substantial post-voting resources and time to count individual ballots and were prone to fraudulent voting with pre-filled fake ballots. Introduction of EVMs have brought down the costs significantly, reduces the time of counting to enable faster announcement of results and eliminated fraudulent practices due to safety features such as security locking, limits to rate of voting per minute and verification of thumb impressions. EVMs are stand-alone machines built with Write once read many memory. They are self-contained, battery-powered and do not need any networking capability. They do not have any wireless or wired internet components and interface.

Various opposition parties at times have alleged faulty EVMs after they failed to defeat the incumbent. In 2011, the Supreme Court of India directed the Election Commission to include a paper trail to help confirm the reliable operation of EVMs. The Election Commission developed EVMs with voter-verified paper audit trail (VVPAT) which was trialed in the 2014 Indian general election. After the 2019 ruling by the Supreme Court, EVMs with accompanying VVPAT are used in all the elections with a small percentage (2%) of the VVPATs verified to ensure the reliability before certifying the final results.

The Election Commission of India had also stated that the machines, system checks, safeguard procedures, and election protocols are fully tamper-proof. To mitigate any doubts regarding the hardware, prior to the election day, a sample number of votes for each political party nominee is entered into each machine, in the presence of polling agents and at the end of this sample trial run, the votes counted and matched with the entered sample votes, to ensure that the machine's hardware has not been tampered with, it is operating reliably and that there were no hidden votes pre-recorded in each machine.

Background
Paper ballots were exclusively used during elections till the 1990s. The printed paper ballots were expensive and required substantial resources for transporting, safely storing them and physically counting individual ballots. Paper ballots were prone to fraudulent voting and booth capturing, where party loyalists captured booths and stuffed them with pre-filled fake ballots. Since the late 1950s, there were multiple documented cases of such activities being reported. The problem grew between the 1950s and 1980s and became a serious and large scale problem in certain states and regions often accompanied with violence. In the late 1970s, Election Commission of India sought a solution for the issues which resulted in the development of Electronic voting machines (EVM).

Design and introduction
The Electronic Voting Machine was proposed in 1977 and Electronics Corporation of India (ECIL) was tasked with the development of the same. In 1979, a working model was evolved and was showcased to various political parties on 6 August 1980. Bharat Electronics (BEL) and ECIL were tasked with manufacturing EVMs. The EVMs were first trialed in 1982 in the by-election to Paravur assembly constituency in Kerala in a limited number of polling stations. In a ruling on a case filed against the usage of EVMs in the by-election, the Supreme Court of India ruled that the sections 59–61 of the Representation of People Act 1951 specified paper ballots and it, therefore, forbade the use of any other technology including electronic voting. The court stated that the use of an alternate technology would require the Indian parliament to amend the law.

Wider adoption
Post the court ruling, as there was no existing law permitting the usage of EVMs, it could not be deployed immediately. In 1989, the Representation of the People Act, 1951 was amended by the Parliament of India to permit the usage of electronic voting. But the deployment was further delayed as general consensus could not be reached with the political parties and other stakeholders on the usage of EVMs. In 1998, the machines were used on an experimental basis across 25 state assembly constituencies during the assembly elections in Rajasthan, Madhya Pradesh and Delhi. In May 2001, EVMs were used in all constituencies for the state assembly elections in Tamil Nadu, Kerala, Puducherry and West Bengal. In 2004, in the General Election, the EVMs were used in all 543 Parliamentary Constituencies for the first time. Since the time, all state assembly and parliamentary elections are held using the EVMs.

Further improvements
As the candidate can know how many people from a polling station exactly voted for him/her, the winning candidate might show favoritism or hold a grudge on specific areas that did not vote for the candidate. In order to mitigate the issue, a totaliser unit was developed in 2008, which can be connected to several control units and would display only the overall results instead of votes from individual machines.

After a ruling by the Supreme Court, the Election Commission appointed an expert technical committee in 2011 to study the feasibility of a Voter-verified paper audit trail (VVPAT) in EVMs to counter the charges of tampering. The committee was tasked to examine the possibility of showing a printed paper to a voter with the symbol of the party to which the vote was cast. On the recommendation of the committee, a VVPAT system was developed and was put on field trials. In July 2011, field trials of the system were conducted at Ladakh, Thiruvananthapuram, Cherrapunjee, East Delhi and Jaisalmer to test the performance under various weather conditions.

Voter-verified paper audit trail (VVPAT) was introduced on a trial basis in a by-poll in September 2013 in Noksen (Assembly Constituency) in Nagaland. It was later used in various Legislative elections and in eight Lok Sabha constituencies in 2014 Indian general election. Following the judgement of the Supreme Court on 8 October 2013, the Election Commission of India introduced VVPATs along with EVMs in a phased manner. In 2019, the Supreme Court directed that a small percentage (2%) of the VVPATs shall be verified to ensure the reliability before certifying the final results.

Design and technology

The EVM was designed by a team led by A.G. Rao and Ravi Poovaiah, professors at IIT Bombay. An EVM consists of two units, a control unit, and the ballot unit which are joined by a cable. The ballot unit consists of labeled buttons which facilitates voting by a voter with the control unit responsible for the operational control of the ballot units, storing of vote counts and display of results on LED displays. The control unit is pre-programmed at the time of manufacturing and cannot be altered later.

The machines are powered by a six volt alkaline battery which enables the use of EVMs without a secondary power source. The designers intentionally opted for battery power, to prevent the possibility of power cables interfering with the functioning and to enable the EVMs to function where a secondary power source is not available. The two units work in tandem and cannot work independently. The EVMs do not have any communication components or internet interface. The ballot unit has an internal clock and a pre-programmed protocol by which it records every input-output event with a timestamp provided it is powered.

An EVM was designed to record a maximum of 3840 votes. A single ballot unit can list 16 candidates and as a part of the initial design, up to four ballot units could be connected in parallel to a single control unit to cater to a maximum of 64 candidates. After an upgrade in 2013, 24 ballot units can now be connected to a single unit so that it can cater to a maximum of 384 candidates. These devices were designed to prevent fraud by limiting the number of new votes can be entered into the machine in a given time frame. In a minute, the EVMs can register a maximum of five votes. The later version of the EVMs are all equipped with VVPAT capability. VVPAT system which was an upgrade of the EVMs had modified software that allowed a printer to be attached to the machine. In June 2018, built-in-hood was added to protect the printer and other devices from excess light and heat in VVPAT systems.

Usage

The EVMs are inventoried and stored at secure locations by the Election Commission. Prior to the election day, a sample number of votes for each political party nominee is entered into each machine, in the presence of polling agents and at the end of this sample trial run, the votes counted and matched with the entered sample votes, to ensure that the machine's hardware has not been tampered with and to prove that it is operating reliably and that there were no hidden votes pre-recorded in each machine.

On an election day, the control unit is operated by the polling booth officer, while the ballot unit is operated by the voter in privacy. The officer confirms the voter's identification before electronically activating the ballot unit to accept a new vote. Once the voter enters the vote, the ballot unit displays the vote to the voter and records it in its memory. Post the voting, the control unit registers the vote on the "close" command of the polling officer post which the process can be repeated. Once a “close” command is issued, the votes already cast in the device's permanent memory cannot be deleted and the device's ability to accept additional votes is disabled mitigating any attempts to open or tamper with the unit. With the VVPAT system, when a vote is cast, it is recorded in its memory and simultaneously a serial number and vote data is printed out for the voter to verify the same. The Election Commission also maintains a database of thumb impressions and electronic voting signatures, open to inspection by polling agent volunteers and outside observers. The system at each booth matches the voter with a registered card with this electronic database in order to ensure that a voter cannot cast a ballot more than once.

After a poll closes on an election day, the units are separated and the control units moved and stored separately in locked and guarded premises. The Presiding officer, at the close of the poll, will hand over to each polling agent present an account of votes recorded. The EVMs are tracked by the Election Commission of India on a real-time basis with a specialized EVM Tracking Software (ETS). The embedded hardware and software enables only a particular control unit to work with a particular voting unit issued by the Election Commission, as another layer of tamper-proofing post the polls have been completed. The machines are also stored under several layers of seals to ensure security and safety.

At the time of counting of votes, the results are displayed on the control unit on pressing the "Result" button. There are built-in safeguards to prevent the accidental pressing of this button before the counting of votes officially begins. This button cannot be pressed before the "Close" button is pressed by the polling officer-in-charge at the end of the voting process and the button is hidden and sealed which is usually exposed only at the counting center in the presence of the designated officer. The total displayed will also be tallied with the count given on the polling day.

Cost and life span
The cost per EVM was inr 5500 at the time the first batch of machines were purchased in 1989–90. The cost was estimated to be inr 10500 per unit as per an additional order issued in 2014. Though the design, production and procurement was capital intensive, it has helped reduce the cost incurred on the printing of ballot papers, their transportation and storage and the counting staff and the remuneration paid to them. EVMs are easier to transport compared to ballot boxes as they are lighter, more portable, and come with polypropylene carrying cases. The shelf life of an EVM is estimated to be 15 years.

Reliability
The use of EVMs, their reliability and speculations about fraud through the use of EVMs have been the subject of many lawsuits before state high courts and the Supreme Court of India. These courts have either dismissed the cases as frivolous or ruled in the favor of the Election Commission and the Supreme Court has declared that the use of EVMs in elections was constitutionally valid.

In February 2010, an international conference held under the chairmanship of Subramanian Swamy blamed the Election Commission for shirking its responsibility on proving the transparency in the working of the EVMs. In April 2010, an independent security analysis was released by a research team led by Hari K. Prasad, Rop Gonggrijp, and Alex Halderman which suggested moving to a voting system that provides greater transparency, such as paper ballots, precinct count optical scan, or a voter verified paper audit trail, since, in any of these systems, skeptical voters could, in principle, observe the physical counting process to gain confidence that the outcome is fair.

A PIL filed in the Supreme Court in 2011 for directing the Election Commission to modify the EVMs to give a slip printed with the symbol of the party in whose favor the voter cast. On 17 January 2012, Delhi High Court in its ruling on Subramanian Swamy's Writ Petition challenging the use of EVMs in the present form asked the Election Commission to hold wider consultations with the executive, political parties and other stake holders on the matter. Following further petitions in the Supreme Court and the subsequent ruling in 2013 led to the use of VVPATs.

The possibility of EVM tampering have been rejected by the Election Commission. The Election Commission and the manufacturers of the EVMs have maintained that the machines are tamper-proof as the programming is done at a secure manufacturing facility and the units have an anti-tamper mechanism by which they become non-operational if it is illegally opened. With no connecting or transmission devices and a real-time logging system, the anti-tamper mechanism in the machine can detect minor changes in time variations.

Election Commission organized an open hackathon on 3 June 2017 encouraging people to attempt hacking of EVMs used by the commission in various Indian elections. While none of them participated, functioning of the EVM and VVPAT machines were demonstrated in the event.

Export to other countries
Nepal, Bhutan, Namibia and Kenya have acquired India-manufactured EVMs. In 2013, the Election Commission of Namibia acquired 1700 control units and 3500 ballot units from India's Bharat Electronics Limited; these units were used in the regional and presidential elections in 2014. Several other Asian and African countries are reportedly interested in using them.

title: Electronic voting in India


text:
Lamin

Lamins, also known as nuclear lamins are fibrous proteins in type V intermediate filaments, providing structural function and transcriptional regulation in the cell nucleus. Nuclear lamins interact with inner nuclear membrane proteins to form the nuclear lamina on the interior of the nuclear envelope. Lamins have elastic and mechanosensitive properties, and can alter gene regulation in a feedback response to mechanical cues. Lamins are present in all animals but are not found in microorganisms, plants or fungi. Lamin proteins are involved in the disassembling and reforming of the nuclear envelope during mitosis, the positioning of nuclear pores, and programmed cell death. Mutations in lamin genes can result in several genetic laminopathies, which may be life-threatening.

History
Lamins were first identified in the cell nucleus, using electron-microscopy. However, they were not recognized as vital components of nuclear structural support until 1975. During this time period, investigations of rat liver nuclei revealed that lamins have an architectural relationship with chromatin and nuclear pores. Later in 1978, immunolabeling techniques revealed that lamins are localized at the nuclear envelope under the inner nuclear membrane. It wasn't until 1986 that an analysis of lamin cDNA clones across a variety of species supported that lamins belong to the intermediate filament (IF) protein family. Further investigations found evidence that supports that all IF proteins arose from a common lamin-like ancestor. This theory is based on the observation that organisms that contain IF proteins necessarily contain lamins as well; however, the presence of lamins is not a requirement for simultaneously containing IF proteins. Furthermore, sequence comparisons between lamins and IF proteins support that an amino-acid sequence that is characteristic of lamins is found in early forms of IF proteins. This sequence is lost in later forms of IF proteins, suggesting that the structure of later intermediate filaments diverged. After this research, investigations of lamins slowed. Studies of lamins became more popular in the 1990s when it was discovered that mutations in the genes that code for lamins can be related to muscular dystrophies, cardiomyopathies, and neuropathies. Current research is being performed to develop treatment methods for the aforementioned laminopathies and to investigate the role lamins play in the aging process.

Structure
The structure of lamins is composed of three units that are common among intermediate filaments: a central α-helical rod domain containing heptad repeats surrounded by globular N and C-terminal domains. The N-terminal is shorter and located at the top (head) while the C-terminal is longer and located at the end (tail). Lamins have a unique structure of the heptad repeats that is continuous in nature and contains an additional six heptads. While the head domain of lamins is fairly consistent, the composition of the tail domain varies based on the type of lamin. However, all C-terminal domains contain a nuclear localization sequence (NLS). Similar to other IF proteins, lamins self-assemble into more complex structures. The basic unit of these structures is a coiled-coil dimer. The dimers arrange themselves in a head-to-tail manner, allowing for the formation of a protofilament. As these protofilaments aggregate, they form lamin filaments. Lamins of higher level organisms, such as vertebrates, continue to assemble into paracrystalline arrays. These complex structures allow nuclear lamins to perform their specialized functions in maintaining the shape of the nucleus as well as roles during mitosis and apoptosis.

A- and B-types
Lamins are divided into two major categories: A- and B-types. These subdivisions are based on similarities in cDNA sequences, structural features, isoelectric points, and expression trends.

A-type lamins
A-type lamins are characterized by a neutral isoelectric point, and they are typically displayed during later stages of embryonic development. Expressed in differentiated cells, A-type lamins originate from the LMNA gene. Two isoforms, lamins A and C, can be created from this gene via alternative splicing. This creates a high amount of homology between the isoforms. Unlike lamin C, Lamin A is generated in a precursor form called prelamin A. Prelamin A and lamin C differ in structure only at the carboxyl-terminus. Here, prelamin A contains two extra exons that lamin C lacks. Furthermore, lamin C contains six unique amino-acid residues while prelamin A contains ninety-eight residues not found in the other isoform. A CaaX motif is found within the unique residues in prelamin A. Due to the presence of the CaaX motif, prelamin A undergoes a series of posttranslational modifications to become mature lamin A. These steps include farnesylation of the carboxyl-terminal cysteine, endoproteolytic release of the terminal amino acids, carboxymethalation of the accessible farnesylcysteine, and removal of the final fifteen residues by a zinc metalloprotease. The very first modification involving farnesylation of prelamin A is crucial to the development of mature lamin A. Isoform lamin C does not undergo posttranslational modifications. Some studies have demonstrated that lamins A and C are not required for the formation of the nuclear lamina, yet disruptions in the LMNA gene can contribute to physical and mental limitations.

B-type lamins
B-type lamins are characterized by an acidic isoelectric point, and they are typically expressed in every cell. As with A-type lamins, there are multiple isoforms of B-type lamins, the most common being lamin B1 and lamin B2. They are produced from two separate genes, LMNB1 and LMNB2. Similar to prelamin A, B-type lamins also contain a CaaX motif at the carboxyl-terminus. This marker triggers the same sequence of posttranslational modifications previously described for prelamin A except for the final cleavage step involving a zinc metalloprotease. Further investigations of B-type lamins across multiple species have found evidence that supports that B-type lamins existed before A-type lamins. This stems from the similarity in structure of B-type lamins between invertebrates and vertebrates. Furthermore, organisms that only contain a single lamin contain a B-type lamin. Other studies that have investigated the structural similarities and differences between A- and B-type lamins have found that the positions of introns/exons in B-type lamins have been conserved in A-type lamins, with more variations in the A-type lamins. This suggests that the common ancestor of these lamin types was a B-type lamin.

Maintenance of nuclear shape
Due to their properties as a type of IF protein, lamins provide support for maintaining the shape of the nucleus. They also play an indirect role in anchoring the nucleus to the endoplasmic reticulum, forming a continuous unit within the cell. This is accomplished by lamin and lamin-interacting proteins (SUN1/SUN2) connecting with proteins on the outer nuclear membrane. These proteins in turn interact with cytoskeletal elements of the endoplasmic reticulum, forming a strong complex that can withstand mechanical stress. Nuclei that lack lamins or have mutated versions have a deformed shape and do not function properly.

Mitosis
During mitosis, lamins are phosphorylated by Mitosis-Promoting Factor (MPF), which drives the disassembly of the lamina and the nuclear envelope. This allows chromatin to condense and the DNA to be replicated. After chromosome segregation, dephosphorylation of nuclear lamins by a phosphatase promotes reassembly of the nuclear envelope.

Apoptosis
Apoptosis is a highly organized process of programmed cell death. Lamins are crucial targets for this process due to their close associations with chromatin and the nuclear envelope. Apoptotic enzymes called caspases target lamins and cleave both A- and B-types. This allows chromatin to separate from the nuclear lamina in order to be condensed. As apoptosis continues, cell structures slowly shrink into compartmentalized "blebs." Finally, these apoptotic bodies are digested by phagocytes. Studies of apoptosis involving mutant A- and B-type lamins that are resistant to cleavage by caspases show decreased DNA condensation and apoptotic “blebbing” formation, thereby underscoring the important role of lamins in apoptosis.

Clinical significance
Mutations in the LMNA gene, encoding Lamins A and C, can produce a series of disorders ranging from muscular dystrophies, neuropathies, cardiomyopathies, and premature ageing syndromes. Collectively, these conditions are known as laminopathies.

Hutchinson-Gilford progeria syndrome
One specific laminopathy is Hutchinson-Gilford progeria syndrome (HGPS), characterized by premature ageing. Those affected by the condition appear normal at birth, but show signs of premature ageing including hair-loss, thinness, joint abnormalities, and weak motor skills as they develop. Furthermore, health problems usually seen in older persons such as atherosclerosis and high blood pressure occur at a much younger age. Those with HGPS typically die in their early teens, usually following a heart attack or stroke.

HGPS is caused by a point mutation in the LMNA gene that codes for lamin A. The genetic alteration results in an alternative splice, creating a mutated form of prelamin A that is much shorter and lacks the cleavage site for a zinc metalloprotease. Because prelamin A cannot be properly processed during posttranslational modifications, it retains its lipid modification (farnesylation) and remains in the inner nuclear membrane. This disrupts the mechanical stability of the nucleus, resulting in a higher rate of cell death and therefore a higher rate of aging. Current studies are investigating the effects of farnesyl-transferase inhibitors (FTIs) to see if farnesyl attachment can be inhibited during posttranslational modification of prelamin A in order to treat patients with HGPS.

Lamin A/C heart disease
Some laminopathies affect heart muscle. These mutations cause a spectrum of heart disease ranging from no apparent effect to severe dilated cardiomyopathy leading to heart failure. Laminopathies frequently cause heart rhythm problems at an early stage in the disease process including abnormally slow heart rhythms such as sinus node dysfunction and atrioventricular block, and abnormally rapid heart rhythms such as ventricular tachycardia. As a result, those with Lamin A/C heart disease are often treated with pacemakers or implantable defibrillators in addition to medication.

title: Lamin


text:
Judas the Zealot

The name Judas the Zealot (Judas Zelotes) is mentioned in the Epistle of the Apostles (Epistula Apostolorum), written in the 2nd century. He is usually identified with the Apostle Simon the Zealot or with the Apostle Jude.

Bruce Metzger, in his Textual Commentary on the Greek NT, comments on Matthew 10:3:

 * "The name Judas Zelotes in several Old Latin manuscripts (compare also the same name in the fifth century mosaic in the great Baptistry at Ravenna) may be a further assimilation to the previous name in Luke's list, "Simon who was called the Zealot.""

title: Judas the Zealot


text:
Honorius of Canterbury

Honorius (died 30 September 653) was a member of the Gregorian mission to Christianize the Anglo-Saxons from their native Anglo-Saxon paganism in 597 AD who later became Archbishop of Canterbury. During his archiepiscopate, he consecrated the first native English bishop of Rochester as well as helping the missionary efforts of Felix among the East Anglians. Honorius was the last to die among the Gregorian missionaries.

Early life
A Roman by birth, Honorius may have been one of those chosen by Pope Gregory the Great for the Gregorian mission to England, although it seems more likely that he was a member of the second party of missionaries, sent in 601. It is not known if his name was given to him at birth or if he chose it when he became archbishop.

Archbishop
In 627, Honorius was consecrated as archbishop by Paulinus of York at Lincoln. Honorius wrote to Pope Honorius I asking the pope to raise the see of York to an archbishopric, so that when one archbishop in England died, the other would be able to consecrate the deceased bishop's successor. The pope agreed, and sent a pallium for Paulinus, but by this time, Paulinus had already been forced to flee from Northumbria. When Paulinus, after the death of King Edwin of Northumbria in October 633, fled Northumbria, he was received by Honorius and appointed to the bishopric of Rochester. The papal letter is dated to June 634, and implies that news of Edwin's death had not reached the pope. This evidence may mean that the traditional date of Edwin's death may need to be moved to October 634. The papal letter may also mean that the traditional date of consecration for Honorius may need re-dating, as the long gap between 627, when he is said to have been consecrated, and 634, when he finally received a pallium, is much longer than usually found. It may be that Honorius was consecrated closer to 634. The papal letter to Honorius is given in the Ecclesiastical History of the medieval writer Bede.

Honorius consolidated the work of converting the English by sending Felix, a Burgundian, to Dunwich after Felix came to the archbishop and made known his desire to go to East Anglia as a missionary. Honorius may have consecrated Felix as the first bishop of East Anglia or Felix may have already been consecrated on the continent. The dating of this episode is unclear, but it is probably close to 631. It is possible that King Sigeberht of East Anglia, who converted to Christianity while he was in exile on the continent, had already met Felix and was behind Felix's journey to Honorius. As well as his help to Felix, Honorius consecrated the first Anglo-Saxon bishop, Ithamar of Rochester, and his successor was also a native of England.

Honorius had few conflicts with the Irish missionary efforts, and admired Aidan, one of the leading Irish clergy.

Death and legacy
Honorius died on 30 September 653, the last of the Gregorian missionaries. He was buried at the Church of St Augustine in Canterbury. He was later revered as a saint, with his feast day being 30 September. His relics were translated to a new tomb in 1091, and around that same time a hagiography of his life was written by Goscelin. In the 1120s his relics were still being venerated at St Augustine's.

title: Honorius of Canterbury


text:
List of cities in the Republic of the Congo

This is a list of cities and towns in the Republic of the Congo with population of 4,000 or more, according to 2007 census.


text:
Hepatocyte

A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in:
 * Protein synthesis
 * Protein storage
 * Transformation of carbohydrates
 * Synthesis of cholesterol, bile salts and phospholipids
 * Detoxification, modification, and excretion of exogenous and endogenous substances
 * Initiation of formation and secretion of bile

Structure
The typical hepatocyte is cubical with sides of 20-30 μm, (in comparison, a human hair has a diameter of 17 to 180 μm). The typical volume of a hepatocyte is 3.4 x 10−9 cm3. Smooth endoplasmic reticulum is abundant in hepatocytes, in contrast to most other cell types.

Microanatomy
Hepatocytes display an eosinophilic cytoplasm, reflecting numerous mitochondria, and basophilic stippling due to large amounts of rough endoplasmic reticulum and free ribosomes. Brown lipofuscin granules are also observed (with increasing age) together with irregular unstained areas of cytoplasm; these correspond to cytoplasmic glycogen and lipid stores removed during histological preparation. The average life span of the hepatocyte is 5 months; they are able to regenerate.

Hepatocyte nuclei are round with dispersed chromatin and prominent nucleoli. Anisokaryosis (or variation in the size of the nuclei) is common and often reflects tetraploidy and other degrees of polyploidy, a normal feature of 30-40% of hepatocytes in the adult human liver. Binucleate cells are also common.

Hepatocytes are organised into plates separated by vascular channels (sinusoids), an arrangement supported by a reticulin (collagen type III) network. The hepatocyte plates are one cell thick in mammals and two cells thick in the chicken. Sinusoids display a discontinuous, fenestrated endothelial cell lining. The endothelial cells have no basement membrane and are separated from the hepatocytes by the space of Disse, which drains lymph into the portal tract lymphatics.

Kupffer cells are scattered between endothelial cells; they are part of the reticuloendothelial system and phagocytose spent erythrocytes. Stellate (Ito) cells store vitamin A and produce extracellular matrix and collagen; they are also distributed amongst endothelial cells but are difficult to visualise by light microscopy.

Protein synthesis
The hepatocyte is a cell in the body that manufactures serum albumin, fibrinogen, and the prothrombin group of clotting factors (except for Factors 3 and 4).

It is the main site for the synthesis of lipoproteins, ceruloplasmin, transferrin, complement, and glycoproteins. Hepatocytes manufacture their own structural proteins and intracellular enzymes.

Synthesis of proteins is by the rough endoplasmic reticulum (RER), and both the rough and smooth endoplasmic reticulum (SER) are involved in secretion of the proteins formed.

The endoplasmic reticulum (ER) is involved in conjugation of proteins to lipid and carbohydrate moieties synthesized by, or modified within, the hepatocytes.

Proteins produced by hepatocytes that function as hormones are known as hepatokines.

Carbohydrate metabolism
The liver forms fatty acids from carbohydrates and synthesizes triglycerides from fatty acids and glycerol. Hepatocytes also synthesize apoproteins with which they then assemble and export lipoproteins (VLDL, HDL).

The liver is also the main site in the body for gluconeogenesis, the formation of carbohydrates from precursors such as alanine, glycerol, and oxaloacetate.

Lipid metabolism
The liver receives many lipids from the systemic circulation and metabolizes chylomicron remnants. It also synthesizes cholesterol from acetate and further synthesizes bile salts. The liver is the sole site of bile salts formation.

Detoxification
Hepatocytes have the ability to metabolize, detoxify, and inactivate exogenous compounds such as drugs (see drug metabolism), insecticides, and endogenous compounds such as steroids.

The drainage of the intestinal venous blood into the liver requires efficient detoxification of miscellaneous absorbed substances to maintain homeostasis and protect the body against ingested toxins.

One of the detoxifying functions of hepatocytes is to modify ammonia into urea for excretion.

The most abundant organelle in liver cells is the smooth endoplasmic reticulum.

Aging
As mammalian liver cells age, damages in their DNA increase in prevalence. A review of the literature indicated that in mouse liver cells DNA damages (single-strand breaks, oxidized bases and 7-methylguanine) increase with age. Also, in rat liver, DNA single- and double-strand breaks, oxidized bases, and methylated bases increase with age; and in rabbit liver, cross-linked bases increase with age. Liver cells depend on DNA repair pathways that specifically protect the transcribed compartment of the genome to promote sustained functionality and cell preservation with age.

Use in research
Primary hepatocytes are commonly used in cell biological and biopharmaceutical research. In vitro model systems based on hepatocytes have been of great help to better understand the role of hepatocytes in (patho)physiological processes of the liver. In addition, pharmaceutical industry has heavily relied on the use of hepatocytes in suspension or culture to explore mechanisms of drug metabolism and even predict in vivo drug metabolism. For these purposes, hepatocytes are usually isolated from animal or human whole liver or liver tissue by collagenase digestion, which is a two-step process. In the first step, the liver is placed in an isotonic solution, in which calcium is removed to disrupt cell-cell tight junctions by the use of a calcium chelating agent. Next, a solution containing collagenase is added to separate the hepatocytes from the liver stroma. This process creates a suspension of hepatocytes, which can be seeded in multi-well plates and cultured for many days or even weeks. For optimal results, culture plates should first be coated with an extracellular matrix (e.g. collagen, Matrigel) to promote hepatocyte attachment (typically within 1-3 hr after seeding) and maintenance of the hepatic phenotype. In addition, and overlay with an additional layer of extracellular matrix is often performed to establish a sandwich culture of hepatocytes. The application of a sandwich configuration supports prolonged maintenance of hepatocytes in culture. Freshly-isolated hepatocytes that are not used immediately can be cryopreserved and stored. They do not proliferate in culture. Hepatocytes are intensely sensitive to damage during the cycles of cryopreservation including freezing and thawing. Even after the addition of classical cryoprotectants there is still damage done while being cryopreserved. Nevertheless, recent cryopreservation and resuscitation protocols support application of cryopreserved hepatocytes for most biopharmaceutical applications.

title: Hepatocyte


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List of cities in Saint Lucia

This is a list of cities, towns, and other inhabited places in the 10 districts of the island country of Saint Lucia. There are 150 inhabited places in Saint Lucia. The significant cities and the district where they are located are listed below.

Cities
The following are the significant cities in Saint Lucia:

title: List of cities in Saint Lucia


text:
User talk:74Noel

Is the Project really reated to Lo Wu? Sorry for asking this foolish question!

title: User talk:74Noel


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Tahoua

Tahoua is a city in Niger and the administrative centre of the Department of Tahoua and the larger Tahoua Region. It is the fourth largest town in the country, with a population of 117,826 (2012 Census).

Overview
The city is primarily a market town for the surrounding agricultural area. It serves as an entrepot for Tuareg merchants from the north and Fulani traders from the south. The town is noted for its production of tchoukou cheese.

It is divided into a pair of urban municipalities: Tahoua I and Tahoua II. The town itself is divided into an old town area, and the Sabon Gari ('new town') area to the north.

History
Tahoua began as a pair of small villages called Bilbis and Fakoua, and began growing from the 17th century on as various groups began migrating to the area, such as the Fulani and Tuareg. Various animist (or Azna) peoples began fleeing to the area to escape persecution from Muslim rulers further north. In 1990, Tahoua was reported to have the lowest HDI score in history, at 0.172.

Demographics
Tahoua is mainly dominated by Hausa, Tuareg ethnic groups.

Transport
Tahoua is served by the Tahoua Airport.

title: Tahoua


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Swallowtail

Swallowtail may refer to:

 * Swallowtail butterfly, large colorful butterflies from the family Papilionidae
 * Swallowtail Butterfly (film), 1996 film directed by Shunji Iwai
 * Swallowtail catastrophe or swallowtail surface, a singularity occurring in the part of mathematics called catastrophe theory
 * Swallow-tail coat, a formal tailcoat worn traditionally as part of the white tie dress code
 * Swallowtail (flag), a term in vexillology
 * Swallowtail joint in woodworking, see Dovetail joint
 * The Swallow's Tail, a painting by Salvador Dalí, inspired by the swallowtail catastrophe
 * Swallowtail, a butler café in Tokyo, Japan
 * Swallowtail, a Wolf Alice song from their debut album My Love Is Cool
 * Swallowtail (album), 2024 album by Jim White and Marisa Anderson

title: Swallowtail


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Heliodorus of Emesa

Heliodorus Emesenus or Heliodorus of Emesa (Ἡλιόδωρος ὁ Ἐμεσηνός) is the author of the ancient Greek novel called the Aethiopica (Αἰθιοπικά) or Theagenes and Chariclea (Θεαγένης καὶ Χαρίκλεια), which has been dated to the 220s or 370s AD.

Identification
He identifies himself at the end of his work as "a Phoenician from Emesa [modern Homs, Syria], of the line of Helios [also translated as: 'from the race of the sun' ], Theodosius' son Heliodorus"

According to Tim Whitmarsh, 'from the race of the sun' "looks like a claim to hereditary priesthood," though "uncertainties" remain. According to The Cambridge History of Classical Literature, "the personal link here established between the writer and Helios has also a literary purpose, as has Calasiris' flashback narrative". The later tradition maintaining that Heliodorus had become a Christian bishop is likely fictional.

Quoting Richard L. Hunter, "The Emesenes were a culturally complex group, including Arab, Phoenician and Greek elements, and, since the third century at any rate, having a connection with the Roman imperial household (the empress Julia Domna was from Emesa, as was the cult of Elagabal which inspired the emperor Heliogabalus)."

title: Heliodorus of Emesa