Hypoxanthine is a occurring purine derivative. It is found as a constituent of nucleic acids, where it is present in the anticodon of tRNA in the form of its nucleoside inosine, it has a tautomer known as 6-hydroxypurine. Hypoxanthine is a necessary additive in certain cell and parasite cultures as a substrate and nitrogen source. For example, it is a required reagent in malaria parasite cultures, since Plasmodium falciparum requires a source of hypoxanthine for nucleic acid synthesis and energy metabolism. In August 2011, a report, based on NASA studies with meteorites found on Earth, was published suggesting hypoxanthine and related organic molecules, including the DNA and RNA components adenine and guanine, may have been formed extraterrestrially in outer space; the Pheretima aspergillum worm, used in Chinese medicine preparations, contains hypoxanthine. It is one of the products of the action of xanthine oxidase on xanthine. However, more in purine degradation, xanthine is formed from oxidation of hypoxanthine by xanthine oxidoreductase.

Hypoxanthine-guanine phosphoribosyltransferase converts hypoxanthine into IMP in nucleotide salvage. Hypoxanthine is a spontaneous deamination product of adenine; because of its resemblance to guanine, the spontaneous deamination of adenine can lead to an error in DNA transcription/replication, as it base pairs with cytosine. Hypoxanthine is removed from DNA by base excision repair, initiated by N-methylpurine glycosylase known as alkyl adenine glycosylase. Hypoxanthine at the US National Library of Medicine Medical Subject Headings

John Stourton, 1st Baron Stourton of Stourton, was an English soldier and politician, elevated to the peerage in 1448. He was born 19 May 1400 at Witham Friary, the son of Sir William de Stourton, Speaker of the House of Commons, by his wife Elizabeth Moigne, daughter and co-heiress of Sir John Moigne of Ower Moigne, Dorset. Stourton served as High Sheriff of Wiltshire in 1426, 1433 and 1437, Somerset and Dorset in 1428 and of Gloucestershire in 1439, he was returned to Parliament as knight of the shire for Wiltshire in Dec 1421, 1425 and 1432 and for Dorset in 1423. He was knighted c. 1430. He was Treasurer of the Household from 1445 to 1453 and fought for five years in the wars in France and Normandy, acting as Lieutenant of Calais from 1450 to 1451. In 1448 he was raised to the peerage of Stourton in the County of Wiltshire. Stourton married Margery Wadham, a daughter of Sir John Wadham of Edge, Devon, of Merryfield, Somerset, of Wadham, Knowstone near South Molton, Devon. Sir John Wadham was MP for Exeter in 1399 and for Devon, as a knight of the shire with Sir Philip Courtenay, in 1401.

He was a Justice of the Common Pleas from 1389 to 1398, ancestor to Nicholas Wadham co-founder of Wadham College, Oxford. Sir John and Margery Stourton had children as follows: William Stourton, 2nd Baron Stourton, married Margaret Chidiock, daughter of Sir John Chidiock and Catherine Lumley. Margaret Stourton, married Sir George Darell of Littlecote, Wiltshire, their daughter, Elizabeth would marry Sir John Seymour, Warden of Savernake Forest, grandfather of Edward Seymour, 1st Duke of Somerset, Thomas Seymour, 1st Baron Seymour of Sudeley, Elizabeth Seymour, Marchioness of Winchester, Sir John Seymour, Jane Seymour, third wife of Henry VIII and mother of Edward VI of England. Sir Reginald Stourton of Stourton, High Sheriff of Wiltshire in 1455–1456 and 1462–1463. Nicholas Stourton John Stourton Joan Stourton, married Richard De La Warr, he was succeeded in the barony by his son William. He was outlived by his wife. History of Parliament biography: STOURTON, John II of Stourton, Wilts Kidd, Williamson, David.

Debrett's Baronetage. New York: St Martin's Press, 1990. Leigh Rayment's Darryl. "FAQ". The Peerage

West Yorkshire Metropolitan Ambulance Service, or'WYMAS', was the NHS ambulance service covering West Yorkshire and the western side of North Yorkshire. On 1 July 2006 it was merged to the single Yorkshire Ambulance Service. West Yorkshire Metropolitan Ambulance Service was formed in 1974, bringing together the individual city services which existed across the county. In 1992, it became an NHS Trust, providing 24-hour emergency and healthcare services to more than 2.1 million people across the region. WYMAS covered the whole of West Yorkshire, including the cities of Bradford and Wakefield, the principal towns of Halifax and Pontefract. In addition, WYMAS' coverage extended into the Craven area of North Yorkshire with ambulance stations at Grassington, Ingleton and Skipton, covering the western side of North Yorkshire and the Yorkshire Dales; the region included parts of the M1, A1, M62, M621 and M606 motorways, West Yorkshire itself is industrial. Neighbouring ambulance services covered Greater Manchester, North Yorkshire and South Yorkshire.

There were 21 ambulance stations situated across the WYMAS operating area. WYMAS activities were centred on two core activities: Accident & Emergency and Patient Transport Services. Both covered areas far and wide, from the rural areas around Settle and Skipton in the North or the Holmfirth and Honley stations in the South. Behind the scenes, WYMAS had an extensive network of services to provide vital support to those on the frontline - everything from finance, human resources and occupational health, to the domestic team and training department. Yorkshire Ambulance Service Emergency medical services in the United Kingdom

Copyright Alert System was a voluntary industry effort to educate and penalize internet users who engage in the unauthorized and unlawful distribution of copyrighted works via peer-to-peer file sharing services. The program was operated by the Center for Copyright Information, a consortium consisting of the Recording Industry Association of America, the Motion Picture Association of America, the internet service providers AT&T, Comcast, Time Warner Cable, Verizon; the CAS used a graduated response system, in which participating ISPs would send warnings notifying subscribers of alleged copyright infringement, as reported by a monitoring service working on behalf of participating copyright owners. The system specified a six-step progression, from advice messages, to warnings that must be acknowledged by the user. After a fifth warning, ISPs were allowed to implement "mitigation measures", which could include penalties such as bandwidth throttling or preventing web access until customers "discuss the matter" with their ISP.

The CAS framework was established on July 2011 after three years in the making. After multiple delays, ISPs began implementing it in late February 2013; the CAS discontinued the program on January 30, 2017. The Center for Copyright Information employed the services of MarkMonitor to detect and monitor suspected copyright infringement activity. Although MarkMonitor monitored many infringement venues, in early 2013 the Electronic Frontier Foundation said it appeared that for purposes of the CAS, the company will only monitor peer-to-peer traffic from public BitTorrent trackers; the Copyright Alert System does not use deep packet inspection. A review of MarkMonitor's system for the CAS stated that only uploads were monitored, with infringement being suspected when MarkMonitor's BitTorrent client obtains pieces of known-infringing content from a peer in the swarm; the pieces were compared to pieces from an already-downloaded copy of the content, matched to content samples supplied by the copyright owners.

When suspected infringement was detected, the ISP for the IP address associated with the suspicious activity was notified. The ISP, in turn, notified the subscriber to whom the IP address was assigned at the time of the alleged infringement, informing the subscriber that their account was suspected of being used to infringe copyright, warning of potential consequences. Users who continue to receive warnings could be issued up to six alerts in the form of pop-up messages and e-mails before stronger measures were taken by the ISP; the Copyright Alert System was intended to be The Center for Copyright Information believed that the Copyright Alert System would be effective in reducing both intentional and unintentional copyright infringement. By providing willing infringers with information regarding the serious consequences of copyright infringement, the CCI hoped to steer would-be infringers to legal online content providers; the CCI hoped that unwitting infringers, such as those whose home networks have been hijacked by unauthorized users or the parents of children who are infringing, would use the knowledge that their account is being used for copyright infringement to force users of the account to curtail these activities.

The CCI hoped to increase parents' involvement in what their children are doing online by alerting misconduct and abuse of their accounts. The EFF claimed the materials used to "educate consumers" were "more like propaganda", that the framework violated the principle of presumption of innocence; the system of alerts was as follows: The first and second alerts notified ISP subscribers that their Internet account has been used for copyright infringement, provided an explanation of how to avoid future offenses, directed users to lawful content sites. If the suspicious behavior persisted, additional alerts were sent; these alerts ask the subscriber to acknowledge receipt of the messages by clicking a notice. After a fifth alert, ISPs were allowed to take "mitigation measures" to prevent future infringement. If the ISP did not institute a mitigation measure following the fifth alert, it had to enact one after the sixth alert. Mitigation measures included: "temporary reductions of Internet speeds, redirection to a landing page until the subscriber contacts the ISP to discuss the matter or reviews and responds to some educational information about copyright, or other measures that the ISP may deem necessary to help resolve the matter".

Mitigation measures varied by company. Verizon was the first to reveal their mitigation policy, their policy specified that violators with more than three alerts would be directed to an online copyright law information. Upon a fifth or sixth alert, the user would experience a temporary speed reduction down to 256kbit/s. According to a leaked internal document, AT&T decided that after a 6th alert, a user's "access to many of the most visited websites restricted" until they completed an "online educational tutorial on copyright". However, AT&T explained that it would not cut the user off the internet though such measure appeared in the copyright warning letter, it gave a reason. Time Warner Cable stated that it would not discontinue customers' service, but instead redirect users to educational pages on copyright law upon multiple violations; the CC

Creative disruption was introduced in 1992 by TBWA's chairman Jean-Marie Dru. It refers to a radical change in a marketplace brought about by the overturning of existing conventions; the term "creative disruption" has both business applications. The word "disruption" was employed in the English language to describe dramatic events such as earthquakes or disturbing news, it was used in a negative sense. On 1 May 1992 Jean-Marie Dru launched the Disruption concept as a marketing tool by publishing a full-page ad headlined "Disruption" in the Wall Street Journal, the Frankfurter Allgemeine and Le Figaro, it explained BDDP's disruptive methodology. Jean-Marie Dru was the first to employ the word in the business world; as it was the first time that the word was given a positive meaning. Since the word was progressively adopted by the business community and has featured in countless press articles in publications such as Forbes, Fast Company, AdAge. In 1996, Jean-Marie Dru published a book entitled Disruption: Overturning Conventions and Shaking Up the Marketplace in which he explained the Disruption methodology.

In 1997, Harvard Business School Professor Clayton Christensen co-authored with Joseph Bower, The Innovator’s dilemma, a book about disruptive technologies and disruptive innovations. The Disruption concept refers to the process of breaking conventions to accelerate movement to the future, without cutting off from the past, it applies to both marketing. As a methodology, it goes one step further than the concept of creative destruction. Professor Clayton Christensen has defined "disruptive innovation", by extension disruption, in a different way. For him, disruption is the process of newcomers penetrating at the low end of a market and moving up the value chain. Jean-Marie Dru has always promoted practical business applications. For him, Disruption, as a practical concept, is about bringing radical change, as opposed to incremental, linear change. Creative disruption is a phrase, used in the marketing world for more than a decade to describe the desired break in existing patterns of behavior of the target audience in response to a creative message.

"Disruption" signals a departure from the norm. Disruptive messaging disrupts the mediocrity in the deluge of advertising the consumer encounters. Creative disruption helps disrupt the normal flow in the way a target processes a massive volume of marketing messaging, so they pause to consider the message they have received. Techniques employed in creative disruption are as boundless as creativity, but may include: Contrasting messaging Unusual or out of place presentation or placement Exaggerated presentation Intensely targeted messagingJean-Marie Dru chairman of TBWA Worldwide gives his own definition of creative disruption in his book entitled Disruption: Overturning Conventions and Shaking Up the Marketplace published in 1996 and translated in twelve languages: "Disruption is a way of thinking defying conventions and creating new visions capable of making our clients' brands grow faster."The aims of creative disruption include: Developing marketing messages which will be remembered and acted upon.

Improving brand perceptions and other market indicators. Disrupting the flow of traditional marketing strategies to make existing business and marketing techniques obsolete. Creating new business innovations that lead to new marketing techniques. Creative disruption has been used as a general business term to denote instituting challenge within a business to break old corporate habits; every business continues to adjust to disruptions, as competitors respond to a business' unique offering. Creative disruption helps a business gain a competitive advantage by seeking tipping points for improvement before competitors replicate and/or improve upon the business model"Creative disruption" as a term is sometimes confused with two other terms: "creative destruction" and "disruptive innovation", but can be differentiated by their goals: In creative destruction, the goal is to tear down/clear away the existing so that a new foundation can be built, the economy can expand. In creative disruption, the goal is to expose flaws in the current business model, highlight areas where improvement/changes are needed, to help inspire adaptation of the business model for future growth.

In disruptive innovation, the goal is to bring about a new market such as the development of the consumer camera in 1888 by Kodak or the use of the internet to conduct online trading for collectibles by eBay in the 1990s. In 1992, Disruption has been registered as a trademark in twelve countries including France, United Kingdom, Germany and Italy. In 2018, TBWA\Group is the owner of the Disruption trademark in 55 countries, including those of the European Union, the United States, India, Brazil, South Africa and Turkey; the Disruption methodology has three parts: convention, disruption. It consists in identifying the cultural conventions around a brand defining a vision for it, lastly developing a disruptive strategy; the purpose of this is to free the brand from existing conventions on the marketplace and to help it grow by building a new and engaging vision. The Disruption method is about breaking conventions, it is not about destroying a market; as TBWA's chairman J

John Scott Trotter known as Uncle John, was an American arranger and orchestra leader. Trotter was best known for conducting the John Scott Trotter Orchestra which backed singer and entertainer Bing Crosby on record and on his radio programs from 1937 to 1954, as well as his work with Vince Guaraldi scoring some of the early Peanuts cartoons. Trotter was born John Scott Jr. on June 14, 1908 in Charlotte, North Carolina. He was born to parents John Scott Lelia Trotter. Trotter attended local schools in Charlotte, he studied piano under Ida Moore Alexander. In 1925, Trotter entered the University of North Carolina, it was there that Trotter began his career as a professional musician playing the piano for a college band led by Hal Kemp. Kemp had entered the university in 1922 and was graduated in 1926, but Trotter withdrew near the end of his first year to join Kemp's band as pianist and arranger, a position he held until 1936. After leaving Kemp's band, Trotter did some work in Hollywood where he handled the orchestrations for Columbia Pictures Pennies from Heaven, his first work with Bing Crosby.

This would start a 17-year professional association with Crosby, although Trotter and Crosby had first met in 1929 in New York City at the Manger Hotel while Crosby was working with Paul Whiteman's orchestra. Trotter recalled the background to his involvement with Pennies from Heaven in an interview with Canadian broadcaster Gord Atkinson, he had been asked by Johnny Burke. This was one of the first independent film productions. Crosby was under contract to Paramount but Pennies from Heaven was done at Columbia as an independent and nobody was set to do the music. Trotter told Burke that seemed to be that. A week Burke asked,'Would you help Arthur Johnston with the piano parts?' After much persuasion, Trotter helped Johnston with the piano parts and fell in love with the score which included Pennies from Heaven, So Do I, One, Button Your Shoe, the Skeleton in the Closet. He decided to complete the orchestrations as the offer was still open. Trotter recalled that the day Pennies from Heaven was recorded, the cameras were rolling with the orchestra on stage.

John Scott Trotter considered that Crosby was a past master of lip syncing but it wasn't done in those days. After completing Pennies from Heaven Trotter went back east.". In July 1937, Trotter replaced Jimmy Dorsey as the musical director for Crosby on NBC's radio program Kraft Music Hall; that same year, Trotter began conducting songs for Crosby's records for Decca. Their first recording together, It's the Natural Thing to Do, reached the No. 2 spot in the charts of the day and they had many hits over the ensuing years. Trotter would remain Crosby's musical director until 1954; the involvement with the Kraft Music Hall came about when Larry Crosby, Bing's brother and public relations director, sent Trotter a wire asking if he could be in Hollywood on June 28, 1937 to take over the orchestra of the Kraft Music Hall on July 8. Although Trotter had rehearsed and directed orchestras, he had never had an orchestra of his own, with his own name; the first time he appeared under his own name'John Scott Trotter and his Orchestra' was on the Kraft Music Hall with Bing Crosby.

The Kraft Music Hall went fifty weeks a year and Trotter did one hundred and forty consecutive Thursdays without missing one. Bing Crosby talked warmly about Trotter in his 1953 autobiography Call Me Lucky and commented about Trotter's remarkable self-control. Trotter had orchestra related responsibilities. Jerry Colonna was a trombonist for future entertainer Spike Jones served as a drummer. Trotter moved on to television, becoming musical director for The George Gobel Show from 1954-60, he served as musical director of several of Crosby's television specials as well as his 1964-65 ABC situation comedy, The Bing Crosby Show. He directed the music for the Charlie Brown cartoon specials. In 1970, Trotter was nominated for an Oscar award and a Grammy award for his musical score for the movie A Boy Named Charlie Brown. Trotter died of cancer on October 29, 1975, at Cedars-Sinai Medical Center in Los Angeles, California, he was buried in Sharon Memorial Park in Charlotte. Surviving him were a sister, Margaret Kinghorn, two brothers and Robert Trotter.

Carroll Carroll, the chief writer of Kraft Music Hall, recalled Trotter's massive volume and appetite when it came to his everyday life. During the war, when home economist M. F. K. Fisher was a guest on the show to plug her wartime conservation cookbook, How to Cook a Wolf, she told Bing that her book explained how to use leftovers; the heartily-fed Trotter stepped to the mike and, in his most polite and gentle North Carolina drawl, asked,'Pardon me, ma'am, but what are left-overs? Trotter, along with Jack Kapp, has been criticized for mainstreaming Crosby's style away from his jazz roots; the reality is that Crosby himself chose the songs he performed on his radio shows and had ultimate approval for anything he recorded to disc. Crosby could have worked with any musical arranger he chose, but he preferred working with Trotter for 17 years. Crosby once said of Trotter.