title: Ezekiel

text: The Quran mentions a prophet called "Dhū al-Kifl" (). Although Dhu al-Kifl's identity is disputed, he is often identified with Ezekiel. Carsten Niebuhr, in his "Reisebeschreibung nach Arabian", says he visited Al Kifl in Iraq, midway between Najaf and Hilla and said "Kifl" was the Arabic form of "Ezekiel". He further explained in his book that Ezekiel's Tomb was present in Al Kifl and that the Jews came to it on pilgrimage. The name "Dhu al-Kifl" means "Possessor of the Double" or "Possesor of the Fold" ( "dhū" "possessor of, owner of" and "al-kifl" "double, folded"). Some Islamic scholars have likened Ezekiel's mission to the description of Dhu al-Kifl. When the exile, monarchy, and state were annihilated, a political and national life was no longer possible. In the absence of a worldly foundation it became necessary to build a spiritual one and Ezekiel performed this mission by observing the signs of the time and deducing his doctrines from them. In conformity with the two parts of his book, his personality and his preaching are alike twofold.


title: Ezekiel

text: Regardless of the identification of Dhu al-Kifl with Ezekiel, Muslims have viewed Ezekiel as a prophet. Ezekiel appears in all Muslim collections of "Stories of the Prophets". Muslim exegesis further lists Ezekiel's father as Buzi ("Budhi") and Ezekiel is given the title "ibn al-‘ajūz", denoting "son of the old (man)", as his parents are supposed to have been very old when he was born. A tradition, which resembles that of Hannah and Samuel in the Hebrew Bible, states that Ezekiel's mother prayed to God in old age for the birth of an offspring and was given Ezekiel as a gift from God.


title: Ezekiel

text: The tomb of Ezekiel is a structure located in modern-day south Iraq near Kefil, believed to be the final resting place of Ezekiel. It has been a place of pilgrimage to both Muslims and Jews alike. After the Jewish exodus from Iraq, Jewish activity in the tomb ceased, although a disused synagogue remains in place.


title: Ezekiel

text: A tomb in the Ergani district of Diyarbakır Province, Turkey, is also believed to be the resting place of prophet Ezekiel. It is located 5 km from the city centre on a hill, revered and visited by the local Muslims, called "Makam Dağı".


title: Ezekiel

text: Ezekiel is portrayed by Darrell Dunham in a 1979 episode of the television series Our Jewish Roots (1978-).


title: Nirmatrelvir

text: Nirmatrelvir is an antiviral medication developed by Pfizer which acts as an orally active 3C-like protease inhibitor. It is part of a nirmatrelvir/ritonavir combination used to treat COVID-19 and sold under the brand name Paxlovid.


title: Nirmatrelvir

text: Coronaviral proteases cleave multiple sites in the viral polyprotein, usually after there are glutamine residues. Early work on related human rhinoviruses showed that the flexible glutamine side chain in inhibitors could be replaced by a rigid pyrrolidone. These drugs had been further developed prior to the COVID-19 pandemic for other diseases including SARS. The utility of targeting the 3CL protease in a real world setting was first demonstrated in 2018 when GC376 (a prodrug of GC373) was used to treat the previously 100% lethal cat coronavirus disease, feline infectious peritonitis, caused by feline coronavirus. Nirmatrelvir and GC373 are both peptidomimetics, share the aforementioned pyrrolidone in P1 position and are competitive inhibitors. They use a nitrile and an aldehyde respectively to bind the catalytic cysteine. Pfizer investigated two series of compounds, with nitrile and benzothiazol-2-yl ketone as the reactive group, respectively, and in the end settled on using nitrile.


title: Nirmatrelvir

text: Nirmatrelvir was developed by modification of the earlier clinical candidate lufotrelvir, which is also a covalent protease inhibitor but its active element is a phosphate prodrug of a hydroxyketone. Lufotrelvir needs to be administered intravenously limiting its use to a hospital setting. Stepwise modification of the tripeptide protein mimetic led to nirmatrelvir, which is suitable for oral administration. Key changes include a reduction in the number of hydrogen bond donors, and the number of rotatable bonds by introducing a rigid bicyclic non-canonical amino acid (specifically, a "fused cyclopropyl ring with two methyl groups"), which mimics the leucine residue found in earlier inhibitors. This residue had previously been used in the synthesis of boceprevir. Tert-leucine (abbreviation: Tle) used in the P3 position of nirmatrelvir was identified first as optimal non-canonical amino acid in potential drug targeting SARS-CoV-2 3C-like protease using combinatorial chemistry (hybrid combinatorial substrate library technology).


title: Nirmatrelvir

text: The leucine-like residue resulted in loss of a nearby contact with a glutamine on the 3C-like protease. To compensate Pfizer tried adding methane sulfonamide, acetamide, and trifluoroacetamide and discovered that of the three, trifluoroacetamide resulted in superior oral bioavailability.


title: Nirmatrelvir

text: In the penultimate step a synthetic homochiral amino acid is coupled with a homochiral amino amide using the water-soluble carbodiimide EDCI as a coupling agent. The resulting intermediate is then treated with Burgess reagent, which dehydrates the amide group to the nitrile of the product.


title: Nirmatrelvir

text: Nirmatrelvir is a covalent inhibitor, binding directly to the catalytic cysteine (Cys145) residue of the cysteine protease enzyme.


title: Nirmatrelvir

text: In the co-packaged medication nirmatrelvir/ritonavir, ritonavir serves to slow the metabolism of nirmatrelvir via cytochrome enzyme inhibition, thereby increasing the circulating concentration of the main drug. This effect is also used in HIV therapy, where ritonavir is used in combination with another protease inhibitor to similarly enhance their pharmacokinetics.


title: Nirmatrelvir

text: In November 2021, Pfizer signed a license agreement with the United Nations–backed Medicines Patent Pool to allow nirmatrelvir to be manufactured and sold in 95 countries. Pfizer stated that the agreement will allow local medicine manufacturers to produce the pill "with the goal of facilitating greater access to the global population". The deal excludes several countries with major COVID-19 outbreaks including Brazil, China, Russia, Argentina, and Thailand.


title: Nirmatrelvir

text: The research that led to nirmatrelvir began on 16 March 2020, when Pfizer formally launched a project at its Cambridge, Massachusetts site to develop antiviral drugs for treating COVID-19. On 22 July 2020, Pfizer chemists were able to synthesize nirmatrelvir for the first time, although the importance of that moment was not clear then because it was just one of 20 candidates synthesized that week. On 1 September 2020, Pfizer completed a pharmacokinetic study in rats which suggested that nirmatrelvir could be administered orally. The actual synthesis of the drug for laboratory research and for clinical trials was carried out at Pfizer's Groton, Connecticut site.


title: Nirmatrelvir

text: In February 2021, Pfizer launched the company's first phase I trial of PF-07321332 (nirmatrelvir) at its clinical research unit in New Haven, Connecticut. According to "Chemical & Engineering News", the drug went "from an idea to the first clinical test in a person in 12 months—a breathtaking pace at which to deliver a bespoke drug candidate."


title: Otaku

text: subculture is a central theme of various anime and manga works, documentaries and academic research. The subculture began in the 1980s as changing social mentalities and the nurturing of traits by Japanese schools combined with the resignation of such individuals to what was then seen as inevitably becoming social outcasts. The subculture's birth coincided with the anime boom, after the release of works such as "Mobile Suit Gundam" before it branched into Comic Market. The subculture continued to grow with the expansion of the internet and media, as more anime, video games, shows, and comics were created. The definition of subsequently became more complex, and numerous classifications of emerged. In 2005, the Nomura Research Institute divided into twelve groups and estimated the size and market impact of each of these groups. Other institutions have split it further or focus on a single interest. These publications classify distinct groups including anime, manga, camera, automobile, idol and electronics . In 2005, the economic impact of was estimated to be as high as ¥2 trillion ( billion).


title: Otaku

text: is derived from a Japanese term for another person's house or family (お宅, ). The word can be used metaphorically, as a part of honorific speech in Japanese as a second-person pronoun. In this usage, its literal translation is "you". It is associated with some dialects of Western Japanese and with housewives, and is less direct and more distant than intimate pronouns, such as "anata", and masculine pronouns, such as "kimi" and "omae".


title: Otaku

text: The origin of the pronoun's use among 1980s manga/anime fans is unclear. Science fiction fans were using "otaku" to address owners of books by the late 1960s (in a sense of "Do[es] [your home] own this book?"). Social critic Eiji Ōtsuka posits that "otaku" was used because it allowed people meeting for the first time, such as at a convention, to interact from a comfortable distance. One theory posits that "otaku" was popularized as a pronoun by science fiction author Motoko Arai in a 1981 essay in "Variety" magazine, and another posits that it was popularized by fans of anime studio Gainax, some of whose founders came from Tottori Prefecture in western Japan (where "otaku" is commonly used). The pronoun was also used in the popular anime "Macross", first aired in 1982, by the characters Hikaru Ichijyo and Lynn Minmay, who address each other as "otaku" until they get to know each other better.


title: Otaku

text: The modern slang form, which is distinguished from the older usage by being written in hiragana (おたく), katakana (オタク or, less frequently, ヲタク) or rarely in rōmaji, first appeared in public discourse in the 1980s, through the work of humorist and essayist Akio Nakamori. His 1983 series , printed in the "lolicon" magazine "Manga Burikko", applied the term as pejorative for "unpleasant" fans, attacking their supposed poor fashion sense and physical appearance in particular. Nakamori was particularly critical of "manga maniacs" oriented to cute girl characters, and explained his label "otaku" as the term of address used between junior high school kids at manga and anime conventions.


title: Otaku

text: In 1989, the case of Tsutomu Miyazaki, "The Otaku Murderer", brought the fandom, very negatively, to national attention. Miyazaki, who randomly chose and murdered four girls, had a collection of 5,763 video tapes, some containing anime and slasher films that were found interspersed with videos and pictures of his victims. Later that year, the contemporary knowledge magazine "Bessatsu Takarajima" dedicated its 104th issue to the topic of . It was called and delved into the subculture of with 19 articles by insiders, among them Akio Nakamori. This publication has been claimed by scholar Rudyard Pesimo to have popularized the term.


title: Otaku

text: In modern Japanese slang, the term is mostly equivalent to "geek" or "nerd" (both in the broad sense; a technological geek would be ) and an academic nerd would be or ), but in a more derogatory manner than used in the West. It is also applied to any fan of any particular theme, topic, hobby or form of entertainment. "When these people are referred to as , they are judged for their behaviors - and people suddenly see an as a person unable to relate to reality." The word entered English as a loanword from the Japanese language. It is typically used to refer to a fan of anime/manga but can also refer to Japanese video games or Japanese culture in general. The American magazine "Otaku USA" popularizes and covers these aspects. The usage of the word is a source of contention among some fans, owing to its negative connotations and stereotyping of the fandom. Widespread English exposure to the term came in 1988 with the release of "Gunbuster", which refers to anime fans as . Gunbuster was released officially in English in March 1990. The term's usage spread throughout the Usenet group rec.arts.anime with discussions about "Otaku no Video"s portrayal of before its 1994 English release. Positive and negative aspects, including the pejorative usage, were intermixed. The term was also popularized by William Gibson's 1996 novel "Idoru", which references .


title: Otaku

text: Morikawa Kaichirō identifies the subculture as distinctly Japanese, a product of the school system and society. Japanese schools have a class structure which functions as a caste system, but clubs are an exception to the social hierarchy. In these clubs, a student's interests will be recognized and nurtured, catering to the interests of . Secondly, the vertical structure of Japanese society identifies the value of individuals by their success. Until the late 1980s, unathletic and unattractive males focused on academics, hoping to secure a good job and marry to raise their social standing. Those unable to succeed socially focused instead on their interests, often into adulthood, with their lifestyle centering on those interests, furthering the creation of the subculture.


title: Otaku

text: Even prior to the coinage of the term, the stereotypical traits of the subculture were identified in a 1981 issue of "Fan Rōdo" (Fan road) about "culture clubs". These individuals were drawn to anime, a counter-culture, with the release of hard science fiction works such as "Mobile Suit Gundam". These works allowed a congregation and development of obsessive interests that turned anime into a medium for unpopular students, catering to obsessed fans. After these fans discovered Comic Market, the term was used as a self-confirming and self-mocking collective identity.


title: Otaku

text: The 1989 "Otaku Murderer" case gave a negative connotation to the fandom from which it has not fully recovered. The identification of turned negative in late 2004 when Kaoru Kobayashi kidnapped, sexually assaulted, and murdered a seven-year-old first-grade student. Japanese journalist Akihiro Ōtani suspected that Kobayashi's crime was committed by a member of the figure moe zoku even before his arrest. Although Kobayashi was not an , the degree of social hostility against increased. were seen by law enforcement as possible suspects for sex crimes, and local governments called for stricter laws controlling the depiction of eroticism in materials.


title: Otaku

text: Not all attention has been negative. In his book, , Hiroki Azuma observed: "Between 2001 and 2007, the forms and markets quite rapidly won social recognition in Japan", citing the fact that "[i]n 2003, Hayao Miyazaki won the Academy Award for his "Spirited Away"; around the same time Takashi Murakami achieved recognition for -like designs; in 2004, the Japanese pavilion in the 2004 International Architecture exhibition of the Venice Biennale (Biennale Architecture) featured . In 2005, the word - one of the keywords of the present volume - was chosen as one of the top ten "buzzwords of the year." The former Prime Minister of Japan Taro Aso has also claimed to be an "otaku", using this subculture to promote Japan in foreign affairs. In 2013, a Japanese study of 137,734 people found that 42.2% self-identify as a type of . This study suggests that the stigma of the word has vanished, and the term has been embraced by many. Marie Kondo told ForbesWomen in 2020: "I credit being an "otaku" with helping me to focus deeply, which definitely contributed to my success."


title: Otaku

text: The district of Akihabara in Tokyo, where there are maid cafés featuring waitresses who dress up and act like maids or anime characters, is a notable attraction center for . Akihabara also has dozens of stores specializing in anime, manga, retro video games, figurines, card games and other collectibles. Another popular location is Otome Road in Ikebukuro, Tokyo. In Nagoya, students from Nagoya City University started a project on ways to help promote hidden tourist attractions related to the culture to attract more to the city.


title: Otaku

text: There are specific terms for different types of , including , a self-mockingly pejorative Japanese term for female fans of , which focuses on homosexual male relationships. are female who are interested in Japanese history. Some terms refer to a location, such as , a slang term meaning "Akihabara-style" which applies to those familiar with Akihabara's culture. Another is , a type of cheering that is part of Akiba-kei. Other terms, such as , literally "painful (cringy) car", describe vehicles decorated with fictional characters, especially bishōjo game or eroge characters.


title: Otaku

text: often participate in self-mocking through the production or interest in humor directed at their subculture. Anime and manga are the subject of numerous self-critical works, such as "Otaku no Video", which contains a live-interview mockumentary that pokes fun at the subculture and includes Gainax's own staff as the interviewees. Other works depict subculture less critically, such as and "Comic Party". A well-known light novel, which later received a manga and anime adaptation, is "Welcome to the N.H.K.", which focuses on the subcultures popular with and highlights other social outcasts such as the and NEETs. Works that focus on an character include "WataMote", the story of an unattractive and unsociable otome game who exhibits delusions about her social status; and "No More Heroes", a video game about an otaku assassin named Travis Touchdown and his surrealistic adventures inspired by anime and manga. Media about otaku also exist outside of Japan, such as the American documentary "Otaku Unite!" which focuses on the American side of the culture, and the Filipino novel "Otaku Girl" which tells the story of a virtual reality world where otaku can role-play and use the powers of their favorite anime characters.


title: Otaku

text: The Nomura Research Institute (NRI) has made two major studies into , the first in 2004 and a revised study with a more specific definition in 2005. The 2005 study defines twelve major fields of interests. Of these groups, manga (Japanese comics) was the largest, with 350,000 individuals and ¥83 billion market scale. Idol were the next largest group, with 280,000 individuals and ¥61 billion. Travel with 250,000 individuals and ¥81 billion. PC with 190,000 individuals and ¥36 billion. Video game with 160,000 individuals and ¥21 billion. Automobile with 140,000 individuals and ¥54 billion. Animation (anime) with 110,000 individuals and ¥20 billion. The remaining five categories include Mobile IT equipment , with 70,000 individuals and ¥8 billion; Audio-visual equipment , with 60,000 individuals and ¥12 billion; camera , with 50,000 individuals and ¥18 billion; fashion , with 40,000 individuals and ¥13 billion; and railway , with 20,000 individuals and ¥4 billion. These values were partially released with a much higher estimation in 2004, but this definition focused on the consumerism and not the "unique psychological characteristics" of used in the 2005 study.


title: Otaku

text: NRI's 2005 study also put forth five archetypes of . The first is the family-oriented , who has broad interests and is more mature than other ; their object of interest is secretive and they are "closet ". The second is the serious "leaving my own mark on the world" , with interests in mechanical or business personality fields. The third type is the "media-sensitive multiple interest" , whose diverse interests are shared with others. The fourth type is the "outgoing and assertive ", who gain recognition by promoting their hobby. The last is the "fan magazine-obsessed ", which is predominately female with a small group of males being the "moe type"; the secret hobby is focused on the production or interest in fan works. The Hamagin Research Institute found that moe-related content was worth ¥88.8 billion ($807 million) in 2005, and one analyst estimated the market could be as much as ¥2 trillion ($18 billion). Japan-based "Tokyo Otaku Mode", a place for news relating to , has been liked on Facebook almost 10 million times.


title: Otaku

text: Other classifications of interests include Vocaloid, cosplay, figures and professional wrestling as categorized by the Yano Research Institute. Yano Research reports and tracks market growth and trends in sectors heavily influenced by consumerism. In 2012, it noted around 30% of growth in dating sim and online gaming , while Vocaloid, cosplay, idols and maid services grew by 10%, confirming its 2011 predictions.


title: Otaku

text: is a Japanese phrase that literally means "a big friend" or "an adult friend". Japanese otaku use it to describe themselves as adult fans of an anime, a manga, or a TV show that is originally aimed at children. Note that a parent who watches such a show with his or her children is not considered an "ōkina otomodachi". An "ōkina otomodachi" is not a parent who buys anime DVDs for his or her children to watch. "Ōkina otomodachi" are those who buy children's anime for themselves. Also, if the work is obviously aimed at adults, a fan of it is not an "ōkina otomodachi". Hence "ōkina otomodachi" and "otaku" are different concepts.


title: HTML5

text: HTML5 is a markup language used for structuring and presenting content on the World Wide Web. It is the fifth and final major HTML version that is a World Wide Web Consortium (W3C) recommendation. The current specification is known as the HTML Living Standard. It is maintained by the Web Hypertext Application Technology Working Group (WHATWG), a consortium of the major browser vendors (Apple, Google, Mozilla, and Microsoft).


title: HTML5

text: HTML5 was first released in a public-facing form on 22 January 2008, with a major update and "W3C Recommendation" status in October 2014. Its goals were to improve the language with support for the latest multimedia and other new features; to keep the language both easily readable by humans and consistently understood by computers and devices such as web browsers, parsers, etc., without XHTML's rigidity; and to remain backward-compatible with older software. HTML5 is intended to subsume not only HTML 4 but also XHTML 1 and DOM Level 2 HTML.


title: HTML5

text: HTML5 includes detailed processing models to encourage more interoperable implementations; it extends, improves, and rationalizes the markup available for documents and introduces markup and application programming interfaces (APIs) for complex web applications. For the same reasons, HTML5 is also a candidate for cross-platform mobile applications because it includes features designed with low-powered devices in mind.


title: HTML5

text: Many new syntactic features are included. To natively include and handle multimedia and graphical content, the new , and elements were added, expandable sections are natively implemented through and rather than depending on CSS or JavaScript, and support for scalable vector graphics (SVG) content and MathML for mathematical formulas was also added. To enrich the semantic content of documents, new page structure elements such as , , , , , , , and are added. New attributes were introduced, some elements and attributes were removed, and others such as , , and were changed, redefined, or standardized. The APIs and Document Object Model (DOM) are now fundamental parts of the HTML5 specification, and HTML5 also better defines the processing for any invalid documents.


title: HTML5

text: The Web Hypertext Application Technology Working Group (WHATWG) began work on the new standard in 2004. At that time, HTML 4.01 had not been updated since 2000, and the World Wide Web Consortium (W3C) was focusing future developments on XHTML 2.0. In 2009, the W3C allowed the XHTML 2.0 Working Group's charter to expire and decided not to renew it.


title: HTML5

text: The Mozilla Foundation and Opera Software presented a position paper at a World Wide Web Consortium (W3C) workshop in June 2004, focusing on developing technologies that are backward-compatible with existing browsers, including an initial draft specification of Web Forms 2.0. The workshop concluded with a vote—8 for, 14 against—for continuing work on HTML. Immediately after the workshop, WHATWG was formed to start work based upon that position paper, and a second draft, Web Applications 1.0, was also announced. The two specifications were later merged to form HTML5. The HTML5 specification was adopted as the starting point of the work of the new HTML working group of the W3C in 2007.


title: HTML5

text: WHATWG's Ian Hickson (Google) and David Hyatt (Apple) produced W3C's first public working draft of the specification on 22 January 2008.


title: HTML5

text: While some features of HTML5 are often compared to Adobe Flash, the two technologies are very different. Both include features for playing audio and video within web pages, and for using Scalable Vector Graphics. However, HTML5 on its own cannot be used for animation or interactivity – it must be supplemented with CSS3 or JavaScript. There are many Flash capabilities that have no direct counterpart in HTML5 (see Comparison of HTML5 and Flash). HTML5's interactive capabilities became a topic of mainstream media attention around April 2010 after Apple Inc.'s then-CEO Steve Jobs issued a public letter titled "Thoughts on Flash" in which he concluded that "Flash is no longer necessary to watch video or consume any kind of web content" and that "new open standards created in the mobile era, such as HTML5, will win". This sparked a debate in web development circles suggesting that, while HTML5 provides enhanced functionality, developers must consider the varying browser support of the different parts of the standard as well as other functionality differences between HTML5 and Flash. In early November 2011, Adobe announced that it would discontinue the development of Flash for mobile devices and reorient its efforts in developing tools using HTML5. On 25 July 2017, Adobe announced that both the distribution and support of Flash would cease by the end of 2020. Adobe itself officially discontinued Flash on 31 December 2020 and all Flash content was blocked from running in Flash Player as of 12 January 2021.


title: HTML5

text: On 14 February 2011, the W3C extended the charter of its HTML Working Group with clear milestones for HTML5. In May 2011, the working group advanced HTML5 to "Last Call", an invitation to communities inside and outside W3C to confirm the technical soundness of the specification. The W3C developed a comprehensive test suite to achieve broad interoperability for the full specification by 2014, which was the target date for recommendation. In January 2011, the WHATWG renamed its "HTML5" specification "HTML Living Standard". The W3C nevertheless continued its project to release HTML5.


title: HTML5

text: In July 2012, WHATWG and W3C decided on a degree of separation. W3C will continue the HTML5 specification work, focusing on a single definitive standard, which is considered a "snapshot" by WHATWG. The WHATWG organization continues its work with HTML5 as a "living standard". The concept of a living standard is that it is never complete and is always being updated and improved. New features can be added but functionality will not be removed.


title: HTML5

text: In December 2012, W3C designated HTML5 as a Candidate Recommendation. The criterion for advancement to W3C Recommendation is "two 100% complete and fully interoperable implementations".


title: HTML5

text: On 16 September 2014, W3C moved HTML5 to Proposed Recommendation. On 28 October 2014, HTML5 was released as a W3C Recommendation, bringing the specification process to completion. On 1 November 2016, HTML5.1 was released as a W3C Recommendation. On 14 December 2017, HTML5.2 was released as a W3C Recommendation.


title: HTML5

text: HTML5.0 was retired on 2018-03-27, along with HTML 3.2, HTML 4.0, HTML 4.01, XHTML™ 1.0, and XHTML™ 1.1. HTML5.2 and HTML5.3 were retired on 2021-01-28.


title: HTML5

text: The W3C ceded authority over the HTML and DOM standards to WHATWG on 28 May 2019, as it considered that having two standards is harmful. The HTML Living Standard is now authoritative. However, W3C will still participate in the development process of HTML.


title: HTML5

text: Before the ceding of authority, W3C and WHATWG had been characterized as both working together on the development of HTML5, and yet also at cross purposes ever since the July 2012 split. The W3C "HTML5" standard was snapshot-based (HTML5, HTML5.1, etc.) and static, while the WHATWG "HTML living standard" is continually updated. The relationship had been described as "fragile", even a "rift", and characterized by "squabbling".


title: HTML5

text: In at least one case, namely the permissible content of the element, the two specifications directly contradicted each other ( with the W3C definition allowing a broader range of uses than the WHATWG definition.


title: HTML5

text: The "Introduction" section in the WHATWG spec (edited by Ian "Hixie" Hickson) is critical of W3C, e.g. " Although we have asked them to stop doing so, the W3C also republishes some parts of this specification as separate documents." In its "History" subsection it portrays W3C as resistant to Hickson's and WHATWG's original HTML5 plans, then jumping on the bandwagon belatedly (though Hickson was in control of the W3C HTML5 spec, too). Regardless, it indicates a major philosophical divide between the organizations:


title: HTML5

text: In addition to the contradiction in the element mentioned above, other differences between the two standards include at least the following, as of September 2018:


title: HTML5

text: The following table provides data from the Mozilla Development Network on compatibility with major browsers, as of September 2018, of HTML elements unique to one of the standards:


title: HTML5

text: The W3C proposed a greater reliance on modularity as a key part of the plan to make faster progress, meaning identifying specific features, either proposed or already existing in the spec, and advancing them as separate specifications. Some technologies that were originally defined in HTML5 itself are now defined in separate specifications:


title: HTML5

text: Some features that were removed from the original HTML5 specification have been standardized separately as modules, such as Microdata and Canvas. Technical specifications introduced as HTML5 extensions such as Polyglot markup have also been standardized as modules. Some W3C specifications that were originally separate specifications have been adapted as HTML5 extensions or features, such as SVG. Some features that might have slowed down the standardization of HTML5 were or will be standardized as upcoming specifications, instead.


title: HTML5

text: HTML5 introduces elements and attributes that reflect typical usage on modern websites. Some of them are semantic replacements for common uses of generic block () and inline () elements, for example (website navigation block), (usually referring to bottom of web page or to last lines of HTML code), or and instead of .


title: HTML5

text: Some deprecated elements from HTML 4.01 have been dropped, including purely presentational elements such as and , whose effects have long been superseded by the more capable Cascading Style Sheets. There is also a renewed emphasis on the importance of client-side JavaScript used to create dynamic web pages.


title: HTML5

text: The HTML5 syntax is no longer based on SGML despite the similarity of its markup. It has, however, been designed to be backward-compatible with common parsing of older versions of HTML. It comes with a new introductory line that looks like an SGML document type declaration, codice_1, which triggers the standards-compliant rendering mode.


title: HTML5

text: Since 5 January 2009, HTML5 also includes "Web Forms 2.0", a previously separate WHATWG specification.


title: HTML5

text: In addition to specifying markup, HTML5 specifies scripting application programming interfaces (APIs) that can be used with JavaScript. Existing Document Object Model (DOM) interfaces are extended and "de facto" features documented. There are also new APIs, such as:


title: HTML5

text: Not all of the above technologies are included in the W3C HTML5 specification, though they are in the WHATWG HTML specification. Some related technologies, which are not part of either the W3C HTML5 or the WHATWG HTML specification, are as follows. The W3C publishes specifications for these separately:


title: HTML5

text: HTML5 cannot provide animation within web pages. Additional JavaScript or CSS3 is necessary for animating HTML elements. Animation is also possible using JavaScript and HTML 4, and within SVG elements through SMIL, although browser support of the latter remains uneven as of 2011.


title: HTML5

text: XML documents must be served with an XML Internet media type (often called "MIME type") such as codice_2 or codice_3, and must conform to strict, well-formed syntax of XML. XHTML5 is simply XML-serialized HTML5 data (that is, HTML5 constrained to XHTML's strict requirements, e.g., not having any unclosed tags), sent with one of XML media types. HTML that has been written to conform to both the HTML and XHTML specifications and therefore produces the same DOM tree whether parsed as HTML or XML is known as polyglot markup.


title: HTML5

text: HTML5 is designed so that old browsers can safely ignore new HTML5 constructs. In contrast to HTML 4.01, the HTML5 specification gives detailed rules for lexing and parsing, with the intent that compliant browsers will produce the same results when parsing incorrect syntax. Although HTML5 now defines a consistent behavior for "tag soup" documents, those documents do not conform to the HTML5 standard.


title: HTML5

text: According to a report released on 30 September 2011, 34 of the world's top 100 Web sites were using HTML5the adoption led by search engines and social networks. Another report released in August 2013 has shown that 153 of the "Fortune 500" U.S. companies implemented HTML5 on their corporate websites.


title: HTML5

text: W3C Working Group publishes "HTML5 differences from HTML 4", which provides a complete outline of additions, removals and changes between HTML5 and HTML4.


title: HTML5

text: On 18 January 2011, the W3C introduced a logo to represent the use of or interest in HTML5. Unlike other badges previously issued by the W3C, it does not imply validity or conformance to a certain standard. As of 1 April 2011, this logo is official.


title: HTML5

text: When initially presenting it to the public, the W3C announced the HTML5 logo as a "general-purpose visual identity for a broad set of open web technologies, including HTML5, CSS, SVG, WOFF, and others". Some web standard advocates, including The Web Standards Project, criticized that definition of "HTML5" as an umbrella term, pointing out the blurring of terminology and the potential for miscommunication. Three days later, the W3C responded to community feedback and changed the logo's definition, dropping the enumeration of related technologies. The W3C then said the logo "represents HTML5, the cornerstone for modern Web applications".


title: HTML5

text: Industry players including the BBC, Google, Microsoft, Apple Inc. have been lobbying for the inclusion of Encrypted Media Extensions (EME), a form of digital rights management (DRM), into the HTML5 standard. As of the end of 2012 and the beginning of 2013, 27 organizations including the Free Software Foundation have started a campaign against including digital rights management in the HTML5 standard. However, in late September 2013, the W3C HTML Working Group decided that Encrypted Media Extensions, a form of DRM, was "in scope" and will potentially be included in the HTML5.1 standard. WHATWG's "HTML Living Standard" continued to be developed without DRM-enabled proposals.


title: HTML5

text: Manu Sporny, a member of the W3C, said that EME would not solve the problem it was supposed to address.


title: HTML5

text: The initial enablers for DRM in HTML5 were Google and Microsoft. Supporters also include Adobe. On 14 May 2014, Mozilla announced plans to support EME in Firefox, the last major browser to avoid DRM. Calling it "a difficult and uncomfortable step", Andreas Gal of Mozilla explained that future versions of Firefox would remain open source but ship with a sandbox designed to run a content decryption module developed by Adobe, later it was replaced with Widevine module from Google which is much more widely adopted by content providers. While promising to "work on alternative solutions", Mozilla's Executive Chair Mitchell Baker stated that a refusal to implement EME would have accomplished little more than convincing many users to switch browsers. This decision was condemned by Cory Doctorow and the Free Software Foundation.


title: British Academy Film Awards

text: The British Academy Film Awards, more commonly known as the BAFTA Film Awards is an annual award show hosted by the British Academy of Film and Television Arts (BAFTA) to honour the best British and international contributions to film. The ceremonies were initially held at the flagship Odeon cinema in Leicester Square in London, before being held at the Royal Opera House from 2007 to 2016. Since 2017, the ceremony has been held at the Royal Albert Hall in London. The statue awarded to recipients depicts a theatrical mask.


title: British Academy Film Awards

text: The first BAFTA Awards ceremony was held in 1949, and the ceremony was first broadcast on the BBC in 1956 with Vivien Leigh as the host. The ceremony was initially held in April or May; since 2001, it typically takes place in February.


title: British Academy Film Awards

text: The British Academy of Film and Television Arts (BAFTA) was founded in 1947 as The British Film Academy, by David Lean, Alexander Korda, Carol Reed, Charles Laughton, Roger Manvell, Laurence Olivier, Emeric Pressburger, Michael Powell, Michael Balcon, and other major figures of the British film industry. In 1958, the Academy merged with The Guild of Television Producers and Directors to form The Society of Film and Television, which eventually became The British Academy of Film and Television Arts in 1976.


title: British Academy Film Awards

text: The stated charitable purpose of BAFTA is to "support, develop and promote the art forms of the moving image, by identifying and rewarding excellence, inspiring practitioners, and benefiting the public". In addition to high-profile awards ceremonies, BAFTA runs a year-round programme of educational events, including film screenings and tribute evenings. BAFTA is supported by a membership of about 6,000 people from the film, television, and video game industries.


title: British Academy Film Awards

text: The Academy's awards are in the form of a theatrical mask designed by American sculptor Mitzi Cunliffe, in response to a commission from the Guild of Television Producers in 1955.


title: British Academy Film Awards

text: The ceremony previously took place in April or May, but since 2001 it has been held in February in order to precede the Academy Awards. Most of the awards are open to all nationalities, though there are awards for Outstanding British Film and Outstanding Debut by a British Writer, Producer or Director. Only UK films are eligible for the categories of The British Short Film and British Short Animation awards.


title: British Academy Film Awards

text: The Awards ceremony is delayed broadcast on British television the same evening, and across the world. The first broadcast was on the BBC in 1956, with Vivien Leigh (who would present an award to her husband Sir Laurence Olivier) as the host. It has been broadcast in colour since 1970. In the US it is shown on BBC America.


title: British Academy Film Awards

text: During each annual ceremony, BAFTA pauses "in memoriam" to pay tribute to those in the industry who have died over the past 12 months, showcasing a montage of images accompanied by music.


title: British Academy Film Awards

text: The award ceremony is held in London. From 2000 to 2007, the ceremonies took place at the flagship Odeon cinema in Leicester Square. Between 2008 and 2016, the ceremonies took place at the Royal Opera House. The 70th Awards in 2017, and subsequent ceremonies, were held at the Royal Albert Hall.


title: British Academy Film Awards

text: Until 2012, the mobile telephone network Orange sponsored the awards. Orange's parent company, EE, took over the sponsorship of the event from 2013.


title: Chlorpromazine

text: Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar disorder, severe behavioral problems in children including those with attention deficit hyperactivity disorder, nausea and vomiting, anxiety before surgery, and hiccups that do not improve following other measures. It can be given orally (by mouth), by intramuscular injection (injection into a muscle), or intravenously (injection into a vein).


title: Chlorpromazine

text: Chlorpromazine is in the typical antipsychotic class, and, chemically, is one of the phenothiazines. Its mechanism of action is not entirely clear but believed to be related to its ability as a dopamine antagonist. It also has anti-serotonergic and antihistaminergic properties.


title: Chlorpromazine

text: Common side effects include movement problems, sleepiness, dry mouth, low blood pressure upon standing, and increased weight. Serious side effects may include the potentially permanent movement disorder tardive dyskinesia, neuroleptic malignant syndrome, severe lowering of the seizure threshold, and low white blood cell levels. In older people with psychosis as a result of dementia it may increase the risk of death. It is unclear if it is safe for use in pregnancy.


title: Chlorpromazine

text: Chlorpromazine was developed in 1950 and was the first antipsychotic on the market. It is on the World Health Organization's List of Essential Medicines. Its introduction has been labeled as one of the great advances in the history of psychiatry. It is available as a generic medication.


title: Chlorpromazine

text: Chlorpromazine is used in the treatment of both acute and chronic psychoses, including schizophrenia and the manic phase of bipolar disorder, as well as amphetamine-induced psychosis.


title: Chlorpromazine

text: In a 2013 comparison of fifteen antipsychotics in schizophrenia, chlorpromazine demonstrated mild-standard effectiveness. It was 13% more effective than lurasidone and iloperidone, approximately as effective as ziprasidone and asenapine, and 12–16% less effective than haloperidol, quetiapine, and aripiprazole.


title: Chlorpromazine

text: A 2014 systematic review carried out by Cochrane included 55 trials that compared the effectiveness of chlorpromazine versus placebo for the treatment of schizophrenia. Compared to the placebo group, patients under chlorpromazine experienced less relapse during 6 months to 2 years follow-up. No difference was found between the two groups beyond two years of follow-up. Patients under chlorpromazine showed a global improvement in symptoms and functioning. The systematic review also highlighted the fact that the side effects of the drug were 'severe and debilitating', including sedation, considerable weight gain, a lowering of blood pressure, and an increased risk of acute movement disorders. They also noted that the quality of evidence of the 55 included trials was very low and that 315 trials could not be included in the systematic review due to their poor quality. They called for further research on the subject, as chlorpromazine is a cheap benchmark drug and one of the most used treatments for schizophrenia worldwide.


title: Chlorpromazine

text: Chlorpromazine has also been used in porphyria and as part of tetanus treatment. It still is recommended for short-term management of severe anxiety and psychotic aggression. Resistant and severe hiccups, severe nausea/emesis, and preanesthetic conditioning are other uses. Symptoms of delirium in hospitalized AIDS patients have been effectively treated with low doses of chlorpromazine.


title: Chlorpromazine

text: Chlorpromazine is occasionally used off-label for treatment of severe migraine. It is often, particularly as palliation, used in small doses to reduce nausea by opioid-treated cancer patients and to intensify and prolong the analgesia of the opioids as well. Efficacy has been shown in treatment of symptomatic hypertensive emergency.


title: Chlorpromazine

text: In Germany, chlorpromazine still carries label indications for insomnia, severe pruritus, and preanesthesia.


title: Chlorpromazine

text: Chlorpromazine and other phenothiazines have been demonstrated to possess antimicrobial properties, but are not currently used for this purpose except for a very small number of cases. For example, Miki "et al." 1992 trialed daily doses of chlorpromazine, reversing chloroquine resistance in "Plasmodium chabaudi" isolates in mice. Weeks "et al.", 2018 find that it also possesses a wide spectrum anthelmintic effect.


title: Chlorpromazine

text: Chlorpromazine is an antagonist of several insect monoamine receptors. It is the most active antagonist known of silk moth ("Bombyx mori") octopamine receptor α, intermediate for "Bm" tyramine receptors 1 & 2, weak for "Drosophila" octopamine receptor β, high for "Drosophila" tyramine receptor 1, intermediate for migratory locust ("Locusta migratoria") tyramine receptor 1, and high for American cockroach ("Periplaneta americana") octopamine receptor α and tyramine receptor 1.


title: Chlorpromazine

text: There appears to be a dose-dependent risk for seizures with chlorpromazine treatment. Tardive dyskinesia (involuntary, repetitive body movements) and akathisia (a feeling of inner restlessness and inability to stay still) are less commonly seen with chlorpromazine than they are with high potency typical antipsychotics such as haloperidol or trifluoperazine, and some evidence suggests that, with conservative dosing, the incidence of such effects for chlorpromazine may be comparable to that of newer agents such as risperidone or olanzapine.


title: Chlorpromazine

text: Very rarely, elongation of the QT interval may occur, increasing the risk of potentially fatal arrhythmias.


title: Chlorpromazine

text: Consuming food prior to taking chlorpromazine orally limits its absorption; likewise, cotreatment with benztropine can also reduce chlorpromazine absorption. Alcohol can also reduce chlorpromazine absorption. Antacids slow chlorpromazine absorption. Lithium and chronic treatment with barbiturates can increase chlorpromazine clearance significantly. Tricyclic antidepressants (TCAs) can decrease chlorpromazine clearance and hence increase chlorpromazine exposure. Cotreatment with CYP1A2 inhibitors like ciprofloxacin, fluvoxamine or vemurafenib can reduce chlorpromazine clearance and hence increase exposure and potentially also adverse effects. Chlorpromazine can also potentiate the CNS depressant effects of drugs like barbiturates, benzodiazepines, opioids, lithium and anesthetics and hence increase the potential for adverse effects such as respiratory depression and sedation.


title: Chlorpromazine

text: Chlorprozamine is also a moderate inhibitor of CYP2D6 and a substrate for CYP2D6, and hence can inhibit its own metabolism. It can also inhibit the clearance of CYP2D6 substrates such as dextromethorphan, potentiating their effects. Other drugs like codeine and tamoxifen, which require CYP2D6-mediated activation into their respective active metabolites, may have their therapeutic effects attenuated. Likewise, CYP2D6 inhibitors such as paroxetine or fluoxetine can reduce chlorpromazine clearance, increasing serum levels of chlorpromazine and potentially its adverse effects. Chlorpromazine also reduces phenytoin levels and increases valproic acid levels. It also reduces propranolol clearance and antagonizes the therapeutic effects of antidiabetic agents, levodopa (a Parkinson's medication. This is likely due to the fact that chlorpromazine antagonizes the D receptor which is one of the receptors dopamine, a levodopa metabolite, activates), amphetamines and anticoagulants. It may also interact with anticholinergic drugs such as orphenadrine to produce hypoglycaemia (low blood sugar).


title: Chlorpromazine

text: Chlorpromazine may also interact with epinephrine (adrenaline) to produce a paradoxical fall in blood pressure. Monoamine oxidase inhibitors (MAOIs) and thiazide diuretics may also accentuate the orthostatic hypotension experienced by those receiving chlorpromazine treatment. Quinidine may interact with chlorpromazine to increase myocardial depression. Likewise, it may also antagonize the effects of clonidine and guanethidine. It also may reduce the seizure threshold and hence a corresponding titration of anticonvulsant treatments should be considered. Prochlorperazine and desferrioxamine may also interact with chlorpromazine to produce transient metabolic encephalopathy.


title: Chlorpromazine

text: Other drugs that prolong the QT interval, such as quinidine, verapamil, amiodarone, sotalol and methadone, may also interact with chlorpromazine to produce additive QT interval prolongation.


title: Chlorpromazine

text: The British National Formulary recommends a gradual withdrawal when discontinuing antipsychotics to avoid acute withdrawal syndrome or rapid relapse. Symptoms of withdrawal commonly include nausea, vomiting, and loss of appetite. Other symptoms may include restlessness, increased sweating, and trouble sleeping. Less commonly, there may be a feeling of the world spinning, numbness, or muscle pains. Symptoms generally resolve after a short period of time.


title: Chlorpromazine

text: There is tentative evidence that discontinuation of antipsychotics can result in psychosis. It may also result in reoccurrence of the condition that is being treated. Rarely, tardive dyskinesia can occur when the medication is stopped.


title: Chlorpromazine

text: Chlorpromazine is classified as a low-potency typical antipsychotic. Low-potency antipsychotics have more anticholinergic side effects, such as dry mouth, sedation, and constipation, and lower rates of extrapyramidal side effects, while high-potency antipsychotics (such as haloperidol) have the reverse profile.


title: Chlorpromazine

text: Chlorpromazine is a very effective antagonist of D2 dopamine receptors and similar receptors, such as D3 and D5. Unlike most other drugs of this genre, it also has a high affinity for D1 receptors. Blocking these receptors causes diminished neurotransmitter binding in the forebrain, resulting in many different effects. Dopamine, unable to bind with a receptor, causes a feedback loop that causes dopaminergic neurons to release more dopamine. Therefore, upon first taking the drug, patients will experience an increase in dopaminergic neural activity. Eventually, dopamine production of the neurons will drop substantially and dopamine will be removed from the synaptic cleft. At this point, neural activity decreases greatly; the continual blockade of receptors only compounds this effect.


title: Chlorpromazine

text: Chlorpromazine acts as an antagonist (blocking agent) on different postsynaptic and presynaptic receptors:


title: Chlorpromazine

text: The presumed effectiveness of the antipsychotic drugs relied on their ability to block dopamine receptors. This assumption arose from the dopamine hypothesis that maintains that both schizophrenia and bipolar disorder are a result of excessive dopamine activity. Furthermore, psychomotor stimulants like cocaine that increase dopamine levels can cause psychotic symptoms if taken in excess.


title: Chlorpromazine

text: Chlorpromazine and other typical antipsychotics are primarily blockers of D2 receptors. In fact an almost perfect correlation exists between the therapeutic dose of a typical antipsychotic and the drug's affinity for the D2 receptor. Therefore, a larger dose is required if the drug's affinity for the D2 receptor is relatively weak. A correlation exists between average clinical potency and affinity of the antipsychotics for dopamine receptors.


title: Chlorpromazine

text: Chlorpromazine tends to have greater effect at serotonin receptors than at D2 receptors, which is notably the opposite effect of the other typical antipsychotics. Therefore, chlorpromazine with respect to its effects on dopamine and serotonin receptors is more similar to the atypical antipsychotics than to the typical antipsychotics.


title: Chlorpromazine

text: Chlorpromazine and other antipsychotics with sedative properties such as promazine and thioridazine are among the most potent agents at α-adrenergic receptors. Furthermore, they are also among the most potent antipsychotics at histamine H1 receptors. This finding is in agreement with the pharmaceutical development of chlorpromazine and other antipsychotics as anti-histamine agents. Furthermore, the brain has a higher density of histamine H1 receptors than any body organ examined which may account for why chlorpromazine and other phenothiazine antipsychotics are as potent at these sites as the most potent classical antihistamines.


title: Chlorpromazine

text: In addition to influencing the neurotransmitters dopamine, serotonin, epinephrine, norepinephrine, and acetylcholine it has been reported that antipsychotic drugs could achieve glutamatergic effects. This mechanism involves direct effects on antipsychotic drugs on glutamate receptors. By using the technique of functional neurochemical assay chlorpromazine and phenothiazine derivatives have been shown to have inhibitory effects on NMDA receptors that appeared to be mediated by action at the Zn site. It was found that there is an increase of NMDA activity at low concentrations and suppression at high concentrations of the drug. No significant difference in glutamate and glycine activity from the effects of chlorpromazine were reported. Further work will be necessary to determine if the influence in NMDA receptors by antipsychotic drugs contributes to their effectiveness.


title: Chlorpromazine

text: Chlorpromazine is an antagonist to H receptors (provoking antiallergic effects), H receptors (reduction of forming of gastric juice), M and M receptors (dry mouth, reduction in forming of gastric juice) and some 5-HT receptors (different anti-allergic/gastrointestinal actions).


title: Chlorpromazine

text: In 1933, the French pharmaceutical company Laboratoires Rhône-Poulenc began to search for new anti-histamines. In 1947, it synthesized promethazine, a phenothiazine derivative, which was found to have more pronounced sedative and antihistaminic effects than earlier drugs. A year later, the French surgeon Pierre Huguenard used promethazine together with pethidine as part of a cocktail to induce relaxation and indifference in surgical patients. Another surgeon, Henri Laborit, believed the compound stabilized the central nervous system by causing "artificial hibernation", and described this state as "sedation without narcosis". He suggested to Rhône-Poulenc that they develop a compound with better stabilizing properties. In December 1950, the chemist Paul Charpentier produced a series of compounds that included RP4560 or chlorpromazine. Simone Courvoisier conducted behavioural tests and found chlorpromazine produced indifference to aversive stimuli in rats.


title: Chlorpromazine

text: Chlorpromazine was distributed for testing to physicians between April and August 1951. Laborit trialled the medicine on at the Val-de-Grâce military hospital in Paris, using it as an anaesthetic booster in intravenous doses of 50 to 100 mg on surgery patients and confirming it as the best drug to date in calming and reducing shock, with patients reporting improved well being afterwards. He also noted its hypothermic effect and suggested it may induce artificial hibernation. Laborit thought this would allow the body to better tolerate major surgery by reducing shock, a novel idea at the time. Known colloquially as "Laborit's drug", chlorpromazine was released onto the market in 1953 by Rhône-Poulenc and given the trade name "Largactil", derived from "large" "broad" and "acti*" "activity".


title: Chlorpromazine

text: Following on, Laborit considered whether chlorpromazine may have a role in managing patients with severe burns, Raynaud's phenomenon, or psychiatric disorders. At the Villejuif Mental Hospital in November 1951, he and Montassut administered an intravenous dose to psychiatrist Cornelia Quarti who was acting as a volunteer. Quarti noted the indifference, but fainted upon getting up to go to the toilet, and so further testing was discontinued (orthostatic hypotension is a known side effect of chlorpromazine). Despite this, Laborit continued to push for testing in psychiatric patients during early 1952. Psychiatrists were reluctant initially, but on 19 January 1952, it was administered (alongside pethidine, pentothal and ECT) to Jacques Lh. a 24-year-old manic patient, who responded dramatically, and was discharged after three weeks having received 855 mg of the drug in total.


title: Chlorpromazine

text: Pierre Deniker had heard about Laborit's work from his brother-in-law, who was a surgeon, and ordered chlorpromazine for a clinical trial at the Sainte-Anne Hospital Center in Paris where he was Men's Service Chief. Together with the Director of the hospital, Professor Jean Delay, they published their first clinical trial in 1952, in which they treated 38 psychotic patients with daily injections of chlorpromazine without the use of other sedating agents. The response was dramatic; treatment with chlorpromazine went beyond simple sedation with patients showing improvements in thinking and emotional behaviour. They also found that doses higher than those used by Laborit were required, giving patients 75–100 mg daily.


title: Chlorpromazine

text: Deniker then visited America, where the publication of their work alerted the American psychiatric community that the new treatment might represent a real breakthrough. Heinz Lehmann of the Verdun Protestant Hospital in Montreal trialled it in 70 patients and also noted its striking effects, with patients' symptoms resolving after many years of unrelenting psychosis. By 1954, chlorpromazine was being used in the United States to treat schizophrenia, mania, psychomotor excitement, and other psychotic disorders.


title: Chlorpromazine

text: Rhône-Poulenc licensed chlorpromazine to Smith Kline & French (today's GlaxoSmithKline) in 1953. In 1955 it was approved in the United States for the treatment of emesis (vomiting). The effect of this drug in emptying psychiatric hospitals has been compared to that of penicillin and infectious diseases. But the popularity of the drug fell from the late 1960s as newer drugs came on the scene. From chlorpromazine a number of other similar antipsychotics were developed. It also led to the discovery of antidepressants.


title: Chlorpromazine

text: Chlorpromazine largely replaced electroconvulsive therapy, hydrotherapy, psychosurgery, and insulin shock therapy. By 1964, about 50 million people worldwide had taken it. Chlorpromazine, in widespread use for 50 years, remains a "benchmark" drug in the treatment of schizophrenia, an effective drug although not a perfect one. The relative strengths or potencies of other antipsychotics are often ranked or measured against chlorpromazine in aliquots of 100 mg, termed "chlorpromazine equivalents" or CPZE.


title: Chlorpromazine

text: Brand names include Thorazine, Largactil, Hibernal, and Megaphen (sold by Bayer in West-Germany since July 1953).)


title: Chlorpromazine

text: Chlorpromazine has tentative benefit in animals infected with "Naegleria fowleri", and shows antifungal and antibacterial activity in vitro.


title: Chlorpromazine

text: Chlorpromazine may be used as an antiemetic in dogs and cats, or, less often, as sedative before anesthesia. In horses, it often causes ataxia and lethargy, and is therefore seldom used.


title: Chlorpromazine

text: It is commonly used to decrease nausea in animals that are too young for other common anti-emetics. It is also sometimes used as a preanesthetic and muscle relaxant in cattle, swine, sheep, and goats.


title: Chlorpromazine

text: The use of chlorpromazine in food-producing animals is not permitted in the EU, as a maximum residue limit could not be determined following assessment by the European Medicines Agency.


title: Monster House (film)

text: Monster House is a 2006 American computer-animated horror film directed by Gil Kenan in his directorial debut and written by Dan Harmon, Rob Schrab and Pamela Pettler, about a neighborhood being terrorized by a sentient haunted house during Halloween. The film features the voices of Mitchel Musso, Sam Lerner, Spencer Locke, Steve Buscemi, Maggie Gyllenhaal, Kevin James, Nick Cannon, Jason Lee, Fred Willard, Jon Heder, Catherine O'Hara, and Kathleen Turner, as well as human characters being animated using live action motion capture stop motion animation, which was previously used in "The Polar Express" (2004). It was Sony's first computer animated film produced by Sony Pictures Imageworks.


title: Monster House (film)

text: Produced by Robert Zemeckis' ImageMovers, Steven Spielberg's Amblin Entertainment (marking their first theatrically-released fully animated film since "Balto") and Relativity Media (their first animated film), the film was released theatrically by Columbia Pictures on July 21, 2006. It received generally positive reviews from critics and grossed $142 million worldwide against a $75 million budget. "Monster House" received a nomination for the Academy Award for Best Animated Feature, but lost to "Happy Feet".


title: Monster House (film)

text: On October 30, 1983, 12-year-old DJ Walters witnesses elderly Horace Nebbercracker confiscating a little girl's tricycle and scaring her away from his house. DJ has documented many similar incidents at the Nebbercracker house, which is across the street from his own. The same day, DJ's parents leave for a convention, placing him in the care of a mean teenage babysitter Zee. Later, DJ's friend Chowder loses a basketball in Nebbercracker's lawn; the boys try to retrieve it, but Nebbercracker stops them. He appears to suffer a heart attack and is taken away by an ambulance.


title: Monster House (film)

text: Zee's inebriated boyfriend Bones arrives. He reveals that, many years ago, Nebbercracker stole his kite. Bones also relates rumors that Nebbercracker ate his wife. After Zee throws him out, Bones notices his kite on Nebbercracker's porch, tries to retrieve it, and is devoured by the house. DJ and Chowder are attacked by the house when they investigate; the next day, they save young Jenny Bennett, who is selling Halloween candy, from being eaten by the house. Jenny calls police officers Landers and Lister, but the house stays quiet when the officers arrive, and they dismiss the report.


title: Monster House (film)

text: The trio consults supernatural expert Reginald "Skull" Skulinski, who speculates the house must be a rare monster created by the merging of a human ghost and a man-made object, only unbound when its heart is destroyed. Concluding Nebbercracker has died and possessed the house, the children construct a dummy child, filling it with cough syrup from Chowder's parents' pharmacy. They offer the dummy to the house to eat, hoping to put the house to sleep so they can find its heart. Landers and Lister arrive and discover the stolen medicine; as they try to arrest the children, the house eats them, the children, the dummy, and the squad car. Separated from the officers, who seem to have vanished, the children explore the sleeping house's basement. They find all the stolen toys, and a shrine to Nebbercracker's wife, Constance the Giantess, whose skeleton is encased in cement. The house awakens and attacks them, but they trigger its gag reflex by grabbing its uvula equivalent, forcing it to vomit them outside.


title: Monster House (film)

text: Nebbercracker returns from the hospital alive, and reveals that Constance is the ghost. When he fell in love with her, she was an unwilling participant in a circus freak show, living in a cage and tormented by people throwing things at her. He helped her escape and married her. On Halloween, during the house's construction, some children threw eggs at her. Frightened and enraged, she grabbed an axe. When Nebbercracker tried to stop her, she stumbled and fell into the unfinished basement to her death, her body accidentally being coated in cement. Nebbercracker finished the house in Constance's memory, but her vengeful ghost merged with it, and she became the Monster House. For the next 45 years, he assumed a hostile demeanor to protect innocent people from her.


title: Monster House (film)

text: DJ convinces Nebbercracker that he needs to let Constance go. Constance, overhearing, uses two trees to lift herself from her foundation and chase the children off. Nebbercracker tries to comfort Constance, and explains everything is for the best, but when she sees he intends to blow her up with dynamite, she attacks him. Chowder uses an excavator to attack Constance and lure her into a pit in a construction site; she falls, but is not destroyed. Jenny lights the dynamite, and DJ swings out on a crane's hook with it, rescuing Chowder while destroying the house with an accurate throw. Freed, Constance's ghost dances with her husband for a moment before ascending to the afterlife. Nebbercracker thanks the three children for freeing him and Constance from their suffering.


title: Monster House (film)

text: That night, the trio and Nebbercracker gather at the house's still-intact basement, returning all the confiscated items. After everyone leaves, Bones emerges from the basement, unharmed, carrying his kite. During the credits, Bones discovers Zee is dating Skull. Meanwhile, everyone else devoured by the house escapes alive.


title: Monster House (film)

text: The film was initially set up at DreamWorks Animation, based on a pitch by newcomer Gil Kenan. Having just finished film school recently, Kenan had been having several meetings with film producers for a while, but he hadn't found any success, with a screenplay based on the "Pac-Man" video game series going unproduced. After Kenan received Dan Harmon's and Rob Schrab's "Monster House" screenplay for ImageMovers, Kenan had a meeting with the head of story Bennett Schneir, where he was able to pitch his vision for the film. Schneir worked for Robert Zemeckis as the head of development at ImageMovers, and Kenan had a meeting with Zemeckis quickly thereafter, apparently due to the filmmakers wanting to get a director for the project as fast as they could. Upon impressing Zemeckis with his pitch, Kenan then had a meeting with Steven Spielberg, meeting during which he pitched the film to Spielberg in a presentation with some sketches and drawings he had drawn before meeting Zemeckis. By 2004, the studio put the film in turnaround, to which Sony Pictures picked up the project and began production on August 23 of that year.


title: Monster House (film)

text: The original screenplay of "Monster House" was, in Kenan's words, "absolutely brilliant and laugh-out-loud funny". Due to his experience as a storyteller, Kenan decided to preserve all the characters and the tone from Harmon's and Schrab's story, but added the idea that the titular house was possessed by a soul, leading to the creation of Constance Nebbercracker and the house's backstory. To help him revise the script and introduce Constance and Horace Nebbercracker into the plot, Kenan brought Pamela Pettler after reading her script for "Corpse Bride" (2005). They worked on the script at her house, and to meet the established deadline, they finished a draft quickly and sent it to Amy Pascal at Columbia Pictures. As work in the screenplay was underway, in a few months of preparation, Kenan had assembled a team of storyboard artists led by Simeon Wilkins in Studio City, Los Angeles to put up rudimentary boards with scratch dialogue and temporal score, with Khang Lee and Chris Appelhans collaborating on paintings for the film.


title: Monster House (film)

text: The film was shot using performance capture, in which the actors performed the characters' movement and lines while linked to sensors, a process pioneered by Zemeckis for his film "The Polar Express" (2004). Zemeckis was in the process of starting filming "The Polar Express" when he met Kenan, who visited the set to see how that film was filmed and discussed with Kenan how they would exactly shoot "Monster House", deciding that they prioritize the story before the filming technology, though Kenan always felt that the story should use animation to create a world with a living house, as he opined that making the house a viable threat and character would better work in an animated setting.


title: Monster House (film)

text: The casting for "Monster House" was a laborious process, especially for the lead trio, who were portrayed by Mitchel Musso, Sam Lerner and Spencer Locke. Kenan agreed with head of animation Troy Saliba that actors should be needed to portray the roles in a believable way. Many of the film's artists interpreted the roles on set and enhanced the lead actors through posed animation that drove the exaggerations of their performances to make them feel subtle and real.


title: Monster House (film)

text: Ed Verreaux served as the production designer of "Monster House". To design the neighbourhood where the story takes place, Verreaux realized that the film's setting needed to resemble that of 1980s films, like "E.T. the Extra-Terrestrial" (1982). During his discussions with Harmon and Schrab, Kenan was told that the film's setting was inspired by that of Wisconsin and Minneapolis. Verreaux and Kenan went together on a scouting trip to design the film's locations, which involved a visit to Universal Studios' backlot, during which they were granted access to the suburban street of "The 'Burbs" (1989), the neighborhood of the show "Desperate Housewives" and the house of "Psycho" (1960).


title: Monster House (film)

text: "Monster House" was the first animated feature film using the Arnold rendering software (co-developed at Sony Pictures Imageworks), and the first feature film entirely rendered with unbiased, brute-force path tracing.


title: Monster House (film)

text: Years after the movie came out, Harmon received a letter from an upset 7-year-old who was displeased with the film. Harmon wrote back that he did not finish the script when the studio took it and hired other writers to change it. He further denounced it by stating that Kenan was a hack and called Spielberg a moron.


title: Monster House (film)

text: As with "The Polar Express", a stereoscopic 3-D version of the film was created and had a limited special release in digital 3-D stereo along with the "flat" version. While "The Polar Express" was produced for the 3-D IMAX 70mm giant film format, "Monster House" was released in approximately 200 theaters equipped for new REAL D Cinema digital 3-D stereoscopic projection. The process was not based on film, but was purely digital. Since the original source material was "built" in virtual 3-D, it created a very rich stereoscopic environment. For the film's release, the studio nicknamed it "Imageworks 3D".


title: Monster House (film)

text: Review aggregation site Rotten Tomatoes gives the film a 75% approval rating, based on 162 reviews with an average rating of 6.8/10. The site's critical consensus reads, ""Monster House" welcoms kids and adults alike into a household full of smart, monstrous fun." On Metacritic the film has a score of 68 out of 100 based on 32 critics, indicating "generally favorable reviews." Audiences polled by CinemaScore gave the film an average grade of "B" on an A+ to F scale.


title: Monster House (film)

text: Roger Ebert gave the film his highest ranking of four stars calling it "one of the most original and exciting animated movies I've seen in a long time" and compared it to the work of Tim Burton. Ian Freer of "Empire" gave the film 4 out of 5 stars, stating "A kind of "Goonies" for the Noughties, "Monster House" is a visually dazzling thrill ride that scales greater heights through its winning characters and poignantly etched emotions. A scary, sharp, funny movie, this is the best kids’ flick of the year so far." Jane Boursaw of Common Sense Media also gave it 4 stars out of 5, saying "This is one of those movies where all the planets align: a top-notch crew (director Gil Kenan; executive producers Steven Spielberg and Robert Zemeckis), memorable voices that fit the characters perfectly; and a great story, ingenious backstory, and twisty-turny ending." Roger Moore of the "Orlando Sentinel" also gave the film four stars out of five, saying "This "Monster House" is a real fun house. It's a 3-D animated kids' film built on classic gothic horror lines, a jokey, spooky "Goonies" for the new millennium." Scott Bowles of "USA Today" gave the film a positive review, saying that "The movie treats children with respect. "Monster" pre-teens are sarcastic, think they're smarter than their parents and are going crazy over the opposite sex". Amy Biancolli of the "Houston Chronicle" wrote, "It's engineered to scare your pants off, split your sides and squeeze your tear ducts into submission." Michael Medved called it "ingenious" and "slick, clever [and] funny" while also cautioning parents about letting small children see it due to its scary and intense nature, adding that a "PG-13 rating would have been more appropriate than its PG rating." A. O. Scott of "The New York Times" commented, "One of the spooky archetypes of childhood imagination—the dark, mysterious house across the street—is literally brought to life in "Monster House," a marvelously creepy animated feature directed by Gil Kenan."


title: Monster House (film)

text: However, the film was not without its detractors. Frank Lovece of "Film Journal International" praised director Gil Kenan as "a talent to watch" but berated the "internal logic [that] keeps changing... D.J.'s parents are away, and the house doesn't turn monstrous in front of his teenage babysitter, Zee. But it does turn monstrous in front of her boyfriend, Bones. It doesn't turn monstrous in front of the town's two cops until, in another scene, it does." In a dismissive review, Todd McCarthy of "Variety" wrote: "Alert 'Harry Potter' fans will notice the script shamelessly lifts the prime personality traits of J. K. Rowling's three most important young characters for its lead trio: Tall, dark-haired, serious-minded DJ is Harry, semi-dufus Chowder is Ron and their new cohort, smarty-pants prep school redhead Jenny (Spencer Locke), is Hermione... it is a theme-park ride, with shocks and jolts provided with reliable regularity. Across 90 minutes, however, the experience is desensitizing and dispiriting and far too insistent."


title: Monster House (film)

text: "Monster House" opened theatrically on July 21, 2006, alongside "Clerks II", "Lady in the Water" and "My Super Ex-Girlfriend", and grossed $22.2 million in its opening weekend, ranking number two at the North American box office behind "". The film ended its theatrical run on October 22, 2006, having grossed $73.7 million in North America and $68.2 million overseas for a worldwide total of $141.9 million against a production budget of $75 million.


title: Monster House (film)

text: A video game based on the film was released by THQ on July 18, 2006 for the PlayStation 2, Nintendo GameCube, Game Boy Advance and Nintendo DS.


title: Anatoly Karpov

text: Anatoly Yevgenyevich Karpov (; born May 23, 1951) is a Russian and former Soviet chess grandmaster, former World Chess Champion, and politician. He was the 12th World Chess Champion from 1975 to 1985, a three-time FIDE World Champion (1993, 1996, 1998), twice World Chess champion as a member of the USSR team (1985, 1989), and a six-time winner of Chess Olympiads as a member of the USSR team (1972, 1974, 1980, 1982, 1986, 1988). The International Association of Chess Press awarded him nine Chess Oscars (1973, 1974, 1975, 1976, 1977, 1979, 1980, 1981, 1984).


title: Anatoly Karpov

text: Karpov's chess tournament successes include over 160 first-place finishes. He had a peak Elo rating of 2780, and his 102 total months at world number one is the third-longest of all time, behind Magnus Carlsen and Garry Kasparov, since the inception of the FIDE ranking list in 1970.


title: Anatoly Karpov

text: Karpov is also an elected Member of the State Duma in Russia. Since 2006, he has chaired the Commission for Ecological Safety and Environmental Protection of the Civic Chamber of the Russian Federation, and since 2007, he has been a member of the Public Council under the Ministry of Defence.


title: Anatoly Karpov

text: Karpov was born into a Russian family on May 23, 1951, in Zlatoust, in the Urals region of the former Soviet Union, and learned to play chess at the age of four. His early rise in chess was swift, as he became a candidate master by age 11. At 12, he was accepted into Mikhail Botvinnik's prestigious chess school, though Botvinnik made the following remark about the young Karpov: "The boy does not have a clue about chess, and there's no future at all for him in this profession."


title: Anatoly Karpov

text: Karpov acknowledged that his understanding of chess theory was very confused at that time, and later wrote that the homework Botvinnik assigned greatly helped him, since it required that he consult chess books and work diligently. Karpov improved so quickly under Botvinnik's tutelage that he became the youngest Soviet master in history at the age of fifteen in 1966; this tied the record established by Boris Spassky in 1952.


title: Anatoly Karpov

text: Karpov finished first in his first international tournament, in Třinec, several months later, ahead of Viktor Kupreichik. In 1967, he won the annual Niemeyer Tournament in Groningen. Karpov won a gold medal for academic excellence in high school, and entered Moscow State University in 1968 to study mathematics. He later transferred to Leningrad State University, eventually graduating from there in economics. One reason for the transfer was to be closer to his coach, grandmaster Semyon Furman, who lived in Leningrad. In his writings, Karpov credits Furman as a major influence on his development as a world-class player.


title: Anatoly Karpov

text: In 1969, Karpov became the first Soviet player since Spassky (1955) to win the World Junior Championship, scoring an undefeated 10/11 in the final A group at Stockholm. This victory earned him the International Master title. In 1970, Karpov tied for fourth and fifth places with Pal Benko at an international tournament in Caracas, Venezuela, and earned the international grandmaster title. FIDE awarded him the title during its 41st congress, held during the Chess Olympiad in Siegen, West Germany in September 1970.


title: Anatoly Karpov

text: Karpov won the 1971 Alekhine Memorial tournament in Moscow (jointly with Leonid Stein), ahead of a star-studded field, for his first significant adult victory. His Elo rating shot from 2540 in 1971 to 2660 in 1973, during which he shared second place in the 1973 Soviet championship, one point behind Spassky, and qualified for the Leningrad Interzonal.


title: Anatoly Karpov

text: Karpov's world junior championship qualified him for one of the two Interzonals, a stage in the 1975 World Championship cycle to choose the challenger to play world champion Bobby Fischer. He finished equal first in the Leningrad Interzonal, qualifying for the 1974 Candidates Matches.


title: Anatoly Karpov

text: Karpov defeated Lev Polugaevsky by the score of +3=5 in the first Candidates' match, earning the right to face former champion Boris Spassky in the semifinal round. Karpov was on record saying that he believed Spassky would easily beat him and win the Candidates' cycle to face Fischer, and that he (Karpov) would win the following Candidates' cycle in 1977. Spassky won the first game as Black in good style, but tenacious, aggressive play from Karpov secured him overall victory by +4−1=6.


title: Anatoly Karpov

text: The Candidates' final was played in Moscow with Victor Korchnoi. Karpov took an early lead, winning the second game against the Sicilian Dragon, then scoring another victory in the sixth game. Following ten consecutive draws, Korchnoi threw away a winning position in the seventeenth game to give Karpov a 3–0 lead. In game 19, Korchnoi succeeded in winning a long endgame, then notched a speedy victory after a blunder by Karpov two games later. Three more draws, the last agreed by Karpov in a clearly better position, closed the match, as he thus prevailed +3−2=19, moving on to challenge Fischer for the world title.


title: Anatoly Karpov

text: Though a world championship match between Karpov and Fischer was highly anticipated, those hopes were never realised. Fischer not only insisted that the match be the first to ten wins (draws not counting), but also that the champion retain the crown if the score was tied 9–9. FIDE, the International Chess Federation, refused to allow this proviso, and gave both players a deadline of April 1, 1975, to agree to play the match under the FIDE-approved rules. When Fischer did not agree, FIDE President Max Euwe declared on April 3, 1975, that Fischer had forfeited his title and Karpov was the new World Champion. Karpov later attempted to set up another match with Fischer, but the negotiations fell through. This thrust the young Karpov into the role of World Champion without having faced the reigning champion.


title: Anatoly Karpov

text: Garry Kasparov argued that Karpov would have had good chances because he had beaten Spassky convincingly and was a new breed of tough professional, and indeed had higher quality games, while Fischer had been inactive for three years. This view is echoed by Karpov himself. Spassky thought that Fischer would have won in 1975, but Karpov would have qualified again and beaten Fischer in 1978.


title: Anatoly Karpov

text: Karpov has said that if he had had the opportunity to play Fischer for the championship in his twenties, he could have been a much better player as a result.


title: Anatoly Karpov

text: Determined to prove himself a legitimate champion, Karpov participated in nearly every major tournament for the next ten years. He convincingly won the Milan tournament in 1975, and captured his first of three Soviet titles in 1976. He created a phenomenal streak of tournament wins against the strongest players in the world. Karpov held the record for most consecutive tournament victories (9) until it was shattered by Garry Kasparov (14). As a result, most chess professionals soon agreed that Karpov was a legitimate world champion.


title: Anatoly Karpov

text: In 1978, Karpov's first title defence was against Viktor Korchnoi, the opponent he had defeated in the 1973–75 Candidates' cycle; the match was played at Baguio, Philippines, with the winner needing six victories.


title: Anatoly Karpov

text: As in 1974, Karpov took an early lead, winning the eighth game after seven draws to open the match. When the score was +5−2=20 in Karpov's favour, Korchnoi staged a comeback, and won three of the next four games to draw level with Karpov. Karpov then won the very next game to retain the title (+6−5=21).


title: Anatoly Karpov

text: Three years later, Korchnoi reemerged as the Candidates' winner against German finalist Robert Hübner to challenge Karpov in Merano, Italy. Karpov handily won this match, 11–7 (+6−2=10), in what is remembered as the "Massacre in Merano".


title: Anatoly Karpov

text: Karpov's tournament career reached a peak at the Montreal "Tournament of Stars" tournament in 1979, where he finished joint first (+7−1=10) with Mikhail Tal ahead of a field of strong grandmasters completed by Jan Timman, Ljubomir Ljubojević, Boris Spassky, Vlastimil Hort, Lajos Portisch, Robert Hübner, Bent Larsen and Lubomir Kavalek. He dominated Las Palmas in 1977 with 13½/15. He also won the prestigious Bugojno tournament in 1978 (shared), 1980 and 1986, the Linares tournament in 1981 (shared with Larry Christiansen) and 1994, the Tilburg tournament in 1977, 1979, 1980, 1982, and 1983, and the Soviet Championship in 1976, 1983, and 1988.


title: Anatoly Karpov

text: Karpov represented the Soviet Union at six Chess Olympiads, in all of which the USSR won the team gold medal. He played as the first reserve at Skopje 1972, winning the board prize with 13/15. At Nice 1974, he advanced to board one and again won the board prize with 12/14. At La Valletta 1980, he was again board one and scored 9/12. At Lucerne 1982, he scored 6½/8 on board one. At Dubai 1986, he scored 6/9 on board two. His last was Thessaloniki 1988, where on board two he scored 8/10. In Olympiad play, Karpov lost only two games out of 68 played.


title: Anatoly Karpov

text: To illustrate Karpov's dominance over his peers as champion, his score was +11−2=20 versus Spassky, +5=12 versus Robert Hübner, +6−1=16 versus Ulf Andersson, +3−1=10 versus Vasily Smyslov, +1=16 versus Mikhail Tal, and +10−2=13 versus Ljubomir Ljubojević.


title: Anatoly Karpov

text: Karpov had cemented his position as the world's best player and world champion by the time Garry Kasparov arrived on the scene. In their first match, the World Chess Championship 1984 in Moscow, the first player to win six games would win the match. Karpov built a 4–0 lead after nine games. The next 17 games were drawn, setting a record for world title matches, and it took Karpov until game 27 to gain his fifth win. In game 31, Karpov had a winning position but failed to take advantage and settled for a draw. He lost the next game, after which 14 more draws ensued. Karpov held a solidly winning position in Game 41, but again blundered and had to settle for a draw. After Kasparov won games 47 and 48, FIDE President Florencio Campomanes unilaterally terminated the match, citing the players' health. Karpov is said to have lost 10 kg over the course of the match. The match had lasted an unprecedented five months, with five wins for Karpov, three for Kasparov, and 40 draws.


title: Anatoly Karpov

text: A rematch was set for later in 1985, also in Moscow. The events of the so-called Marathon Match forced FIDE to return to the previous format, with a match limited to 24 games (with Karpov remaining champion if the match finished 12–12). Karpov needed to win the final game to draw the match and retain his title, but lost, surrendering the title to his opponent. The final score was 13–11 (+3−5=16) in favour of Kasparov.


title: Anatoly Karpov

text: Karpov remained a formidable opponent (and the world No. 2) until the mid-1990s. He fought Kasparov in three more world championship matches in 1986 (held in London and Leningrad), 1987 (in Seville), and 1990 (in New York City and Lyon). All three matches were extremely close: the scores were 11½–12½ (+4−5=15), 12–12 (+4−4=16), and 11½–12½ (+3−4=17). In all three matches, Karpov had winning chances up to the last games. The ending of the 1987 Seville match was particularly dramatic. Karpov won the 23rd game when Kasparov miscalculated a combination. In the final game, needing only a draw to win the title, Karpov cracked under time pressure at the end of the first session of play, missed a variation leading to an almost forced draw, and allowed Kasparov to adjourn the game with an extra pawn. After a further mistake in the second session, Karpov was slowly ground down and resigned on move 64, ending the match and allowing Kasparov to keep the title.


title: Anatoly Karpov

text: In their five world championship matches, Karpov scored 19 wins, 21 losses, and 104 draws in 144 games. Overall, Karpov played five matches against Kasparov for the title from 1984 to 1990 without ever defeating him in a match.


title: Anatoly Karpov

text: In 1992, Karpov lost a Candidates Match against Nigel Short. But in the World Chess Championship 1993, Karpov reacquired the FIDE World Champion title when Kasparov and Short split from FIDE. Karpov defeated Timman – the loser of the Candidates' final against Short.


title: Anatoly Karpov

text: The next major meeting of Kasparov and Karpov was the 1994 Linares chess tournament. The field, in eventual finishing order, was Karpov, Kasparov, Shirov, Bareev, Kramnik, Lautier, Anand, Kamsky, Topalov, Ivanchuk, Gelfand, Illescas, Judit Polgár, and Beliavsky; with an average Elo rating of 2685, the highest ever at that time. Impressed by the strength of the tournament, Kasparov had said several days before the tournament that the winner could rightly be called the world champion of tournaments. Perhaps spurred on by this comment, Karpov played the best tournament of his life. He was undefeated and earned 11 points out of 13 (the best world-class tournament winning percentage since Alekhine won San Remo in 1930), finishing 2½ points ahead of second-place Kasparov and Shirov. Many of his wins were spectacular (in particular, his win over Topalov is considered possibly the finest of his career). This performance against the best players in the world put his Elo rating tournament performance at 2985, the highest performance rating of any player in history up until 2009, when Magnus Carlsen won the category XXI Pearl Spring chess tournament with a performance of 3002. Chess statistician Jeff Sonas considers Karpov's Linares performance the best tournament result in history.


title: Anatoly Karpov

text: Karpov defended his FIDE title against the rising star Gata Kamsky (+6−3=9) in 1996. In 1998, FIDE largely scrapped the old system of Candidates' Matches, instead having a large knockout event in which a large number of players contested short matches against each other over just a few weeks. In the first of these events, the FIDE World Chess Championship 1998, champion Karpov was seeded straight into the final, defeating Viswanathan Anand (+2−2=2, rapid tiebreak 2–0). In the subsequent cycle, the format was changed, with the champion having to qualify. Karpov refused to defend his title, and ceased to be FIDE World Champion after the FIDE World Chess Championship 1999.


title: Anatoly Karpov

text: Karpov's classical tournament play has been seriously limited since 1997, since he prefers to be more involved in Russian politics. He had been a member of the Supreme Soviet Commission for Foreign Affairs and the president of the Soviet Peace Fund before the Soviet Union dissolved. In addition, he has been involved in several disputes with FIDE. In the September 2009 FIDE rating list, he dropped out of the world's Top 100 for the first time.


title: Anatoly Karpov

text: Karpov usually limits his play to exhibition events, and has revamped his style to specialize in rapid chess. In 2002, he won a match against Kasparov, defeating him in a rapid time control match 2½–1½. In 2006, he tied for first with Kasparov in a blitz tournament, ahead of Korchnoi and Judit Polgár.


title: Anatoly Karpov

text: Karpov and Kasparov played a mixed 12-game match from September 21–24, 2009, in Valencia, Spain. It consisted of four rapid (or semi-rapid) and eight blitz games and took place exactly 25 years after the two players' legendary encounter at the World Chess Championship 1984. Kasparov won the match 9–3.


title: Anatoly Karpov

text: Karpov played a match against Yasser Seirawan in 2012 in St. Louis, Missouri, an important center of the North American chess scene, winning 8–6 (+5−3=6).


title: Anatoly Karpov

text: In November 2012, he won the Cap d'Agde rapid tournament that bears his name (Anatoly Karpov Trophy), beating Vasyl Ivanchuk (ranked 9th in the October 2012 FIDE world rankings) in the final.


title: Anatoly Karpov

text: In 2003, Karpov opened his first American chess school in Lindsborg, Kansas. On March 2, 2022, the school announced a name change to International School of Chess of the Midwest due to the 2022 Russian invasion of Ukraine.


title: Anatoly Karpov

text: Karpov has been a member of the sixth, seventh and eighth Russian State Dumas. Since 2005, he has been a member of the Public Chamber of Russia. He has involved himself in several humanitarian causes, such as advocating the use of iodised salt. On December 17, 2012, Karpov supported the law in the Russian Parliament banning adoption of Russian orphans by U.S. citizens.


title: Anatoly Karpov

text: Karpov expressed support of the annexation of Crimea by the Russian Federation, and accused Europe of trying to demonize Putin. In August 2019, Maxim Dlugy said that Karpov had been waiting since March for the approval of a non-immigrant visa to the United States, despite frequently visiting the country since 1972. Karpov had been scheduled to teach a summer camp at the Chess Max Academy. Dlugy said that Karpov had been questioned at the US embassy in Moscow about whether he planned to communicate with American politicians. Karpov was among the Russian State Duma members placed under sanctions by the EU during the prelude to the 2022 Russian invasion of Ukraine. In March 2022, after the start of the invasion, the FIDE Council suspended Karpov's title of FIDE Ambassador for Life.


title: Anatoly Karpov

text: In November 2022, Karpov received a head injury that left him concussed; according to some sources, he was placed in an induced coma. Sources vary on the cause of the injury, including allegations that he was attacked while heavily intoxicated. Karpov's daughter Sofia claimed that he had accidentally fallen; this was echoed by the Russian Chess Federation.


title: Anatoly Karpov

text: In March 2010 Karpov announced that he would be a candidate for the presidency of FIDE. The election took place in September 2010 at the 39th Chess Olympiad. In May, a fund-raising event took place in New York with the participation of Kasparov and of Magnus Carlsen, both of whom supported his bid and campaigned for him. Nigel Short also supported Karpov's candidacy. On September 29, 2010, Kirsan Ilyumzhinov was reelected as president of FIDE, 95 votes to 55.


title: Anatoly Karpov

text: Karpov's "boa constrictor" playing style is solidly positional, taking minimal risks but reacting mercilessly to the slightest error by his opponent. As a result, he is often compared to José Raúl Capablanca, the third world champion. Karpov himself describes his style as follows:Let us say the game may be continued in two ways: one of them is a beautiful tactical blow that gives rise to variations that don't yield to precise calculations; the other is clear positional pressure that leads to an endgame with microscopic chances of victory... I would choose [the latter] without thinking twice. If the opponent offers keen play I don't object; but in such cases I get less satisfaction, even if I win, than from a game conducted according to all the rules of strategy with its ruthless logic.


title: Anatoly Karpov

text: Karpov's extensive stamp collection of Belgian philately and Belgian Congo stamps and postal history covering mail from 1742 through 1980 was sold by David Feldman's auction company between December 2011 and 2012. He is also known to have large chess stamp and chess book collections. His private chess library consists of 9,000 books.


title: Muhammad ibn Musa al-Khwarizmi

text: Muḥammad ibn Mūsā al-Khwārizmī (; ), or al-Khwarizmi, was a Persian polymath from Khwarazm, who produced vastly influential works in mathematics, astronomy, and geography. Around 820 CE, he was appointed as the astronomer and head of the library of the House of Wisdom in Baghdad.


title: Muhammad ibn Musa al-Khwarizmi

text: Al-Khwarizmi's popularizing treatise on algebra ("The Compendious Book on Calculation by Completion and Balancing", c. 813–833 CE) presented the first systematic solution of linear and quadratic equations. One of his principal achievements in algebra was his demonstration of how to solve quadratic equations by completing the square, for which he provided geometric justifications. Because he was the first to treat algebra as an independent discipline and introduced the methods of "reduction" and "balancing" (the transposition of subtracted terms to the other side of an equation, that is, the cancellation of like terms on opposite sides of the equation), he has been described as the father or founder of algebra. The term "algebra" itself comes from the title of his book (the word "al-jabr" meaning "completion" or "rejoining"). His name gave rise to the terms "algorism" and "algorithm," as well as Spanish, Italian and Portuguese terms "algoritmo," and Spanish "guarismo" and Portuguese "algarismo" meaning "digit".


title: Muhammad ibn Musa al-Khwarizmi

text: In the 12th century, Latin translations of his textbook on arithmetic ("Algorithmo de Numero Indorum") which codified the various Indian numerals, introduced the decimal positional number system to the Western world. "The Compendious Book on Calculation by Completion and Balancing", translated into Latin by Robert of Chester in 1145, was used until the sixteenth century as the principal mathematical text-book of European universities.


title: Muhammad ibn Musa al-Khwarizmi

text: In addition to his best-known works, he revised Ptolemy's "Geography", listing the longitudes and latitudes of various cities and localities. He further produced a set of astronomical tables and wrote about calendaric works, as well as the astrolabe and the sundial. He also made important contributions to trigonometry, producing accurate sine and cosine tables, and the first table of tangents.


title: Muhammad ibn Musa al-Khwarizmi

text: Few details of al-Khwārizmī's life are known with certainty. Ibn al-Nadim gives his birthplace as Khwarazm, and he is generally thought to have come from this region. His name means 'the native of Khwarazm', a region that was part of Greater Iran, and is now part of Turkmenistan, and Uzbekistan.


title: Muhammad ibn Musa al-Khwarizmi

text: Muhammad ibn Jarir al-Tabari gives his name as Muḥammad ibn Musá al-Khwārizmī al-Majūsī al-Quṭrubbullī (). The epithet "al-Qutrubbulli" could indicate he might instead have come from Qutrubbul (Qatrabbul), a viticulture district near Baghdad. However, Rashed denies this: