title: Nick Joaquin

text: A theological theme revealed in the Early Joaquin works is the emphasis on history and time. These are evident, according to critics, in works such as “May Day Eve”. “Guardia de Honor”, and “The Order of Melchizedek” and while not as obvious, were present as thematic backgrounds in “Doña Jeronima”, “The Legend of the Dying Wanton”, “The Summer Solstice”, and “The Mass of St. Sylvestre”. This theme comes in the form of fixation with time and patterns of recurrence as described by critics as nostalgia, which is said to show emphasis on the past. Critics make a connection of this theological reality used by Nick Joaquin to reflect Philippine culture and the intermingling of Christian and pagan values.


title: Nick Joaquin

text: According to critics, Nick Joaquin is said to be a writer who sees the essence of being Filipino in the return to the Filipino's pre-Hispanic past. National identity is a very important topic for Nick Joaquin as evident in his works such as La Naval de Manila, After the Picnic and Summer Solstice. Noticeably in his works namely After the Picnic and Summer Solstice, the recurring theme of the rejection of the colonial self can be seen in the conflicts of the protagonist such as Chedeng, from After the Picnic, to reject Father Chavez's white-ego-ideals. In Chedeng's attempt to assert one's identity through rejection of the colonial self-imposed by society, she is confronted into choosing whether she would obliged with the white-ego ideal which asserts her security or rejection of the white-ego-ideal. Nick Joaquin also, every now and then, motleys this theme with other themes such as gender conflict, which can be evident in After the Picnic and Summer Solstice. A good example of Nick Joaquin's blending of themes is Summer Solstice, wherein he conflates gender conflict with colonial conflict, noticeable in the assertion of Doña Lupeng in the reclamation of the power of patriarchy by womanhood.


title: Nick Joaquin

text: Tropical Gothic was reviewed in Philippine studies by H.B. Furay, Lourdes Busuego Pabo, and Emmanuel Lacaba. Critics describe this as the end of what they refer to as the Early Joaquin.


title: Nick Joaquin

text: Attempting to characterize stories of Tropic Goth as what critics referred to as a product of the Early Nick Joaquin would be deceptive for it was written, along with majority of his works, during the thirties. Critics referred to the publication years of 1946 -1966 as most significant in terms of the works produced. They also referred to these years as the time wherein Nick Joaquin was recognized as a first rank writer in the Philippines. Works included in these years include “Prose and Poems” (1952), three stories in the “Free Press” (1965 - 1966) and The portrait of the Artist as a Filipino. Included in the first edition of Nick Joaquin's “Prose and Poems” were the titles “The Woman Who had Two Navels” (1961) and “La Naval de Manila” (1964).


title: Nick Joaquin

text: Emmanuel Lacaba, member of Philippine Studies, argues that the three Free Press Stories known as “Candido’s Apocalypse”, “"Doña Jeronima”, and “The Order of Melchizedek”, were considered works under the older Nick Joaquin given the gap between these works and the earlier stories of “Prose and Poems”. Despite the gap, Lacaba argues that there is a recurring theme present in the later works of Nick Joaquin. In Emmanuel Lacaba's criticism, he mentions the radical change in language, mainly through the dialogue used. Early Nick Joaquin, as Lacaba described through the example of Tropical Goth, made use of “lush” language as well as “baroque” once the readers get past the words used. Similar cases for “Candido’s Apocalypse” and “The Order of Melchizedek” which show more similarities than differences in the way of sentence patterns used.


title: Nick Joaquin

text: Critics, such as Furay, define Early Nick Joaquin through his nine stories of Tropic Gothic which emphasizes his talents in Philippine writing in English. Additionally, through the mention of works such as “Prose and Poems” (1952) and the three additional “Free Press stories” (1972), critics argue that the greatness of his writing lies in his themes used as well as deep intellectual analysis of Philippine culture embedded in his writing style.


title: Nick Joaquin

text: The Late Nick Joaquin is defined by critics as the time 10 years after his absence from the field of fiction. These years, as defined by Lacaba, were about Joaquin devoting himself entirely to Free Press and journalistic writing. This was defined by Joaquin the essayist. He wrote under the pseudonym of Quijano de Manila. The beginning of Late Joaquin was seen after he had published two significant essays and three plays after 1975. Publications of Late Joaquin still deal with similar themes of history, paganism and Christianity and morality. His published article, The Manila Review on “Culture of History” represent his philosophy of the past which underlies many of his early works. Critics emphasizes that in the later works, there is a sharper emphasis on freedom and choice as seen in his publication in December 1975 titled “Fathers and Sons: A Melodrama in Three Reels” which was a dramatization of his earlier story “Three Generations”.


title: Nick Joaquin

text: Nick Joaquin's name as a literary artist is considered, by different university professors, as a key figure in Philippine literature in English due to the imparted truths of his writing. In his different works, Nick Joaquin has presented objective realities about different events and people capturing both their good and bad qualities. In his essays, Nick Joaquin is said to employ real life situations through symbolic qualities reflecting certain social and cultural values. This is done through the subject selection and form of writing chosen which are considered by many different fellow artists as unique. In terms of the development of the English language, Nick Joaquin was able to contribute to this by adding Filipino feelings, values, and nuances. Literary writers have mentioned how he was able to preserve the culture of the Filipinos through the use of a different tongue. The English language used by Nick Joaquin became a medium to express his literary artistry and Filipino Patriotism. Nick Joaquin was able to publish a large body of literary works during his time and through this, he has had great contribution to Philippine literature in English.


title: Nick Joaquin

text: Nick Joaquin's foray into literary journalism involved bringing together his two careers. Joaquin argued that Philippine letters during the 1950s and 1960s were polarized into extremes: literature and journalism. Joaquin, under the name of Quijano de Manila during that time, belonged to both worlds as found in his works. According to different studies on literary journalism, works of Nick Joaquin serve as examples of social sciences applied to the arts. This was further seen in his work “Philippine letters’ Dr Jekyll and Mr Hyde which, according to scholars, showed de Manila's career which oscillates between fiction and non-fiction. It was during 1960 wherein Nick Joaquin entered journalism from being a fiction writer. It was under the name of de Manila wherein he began to publish reportage in a literary journalistic style. This was then referred to as, he claimed, “New Journalism” in the United States according to the Philippine Daily Inquirer. Different literary scholars claim that the works of Nick Joaquin as de Manila exemplifies what he quotes as “good reportage with grace of style”. One of de Manila's publication, “The House on Zapote Street”, was termed journalism by the author but is read much like his fictional works under the name Nick Joaquin.


title: Uniforms of the United States Space Force

text: The uniforms of the United States Space Force are the standardized military uniforms worn by U.S. Space Force personnel, known as guardians.


text: The Space Force's interim service dress uniform was inherited from the U.S. Air Force, which was adopted by Air Force chief of staff General Ronald Fogleman in 1994, replacing earlier blue service dress uniforms, and will continue to be used until the conclusion of the uniform tests. The Space Force service dress uniform is distinguished from Air Force service dress by a distinctive U.S. Space Force lapel insignia.


text: The uniform coat is single-breasted with three buttons and has one welt pocket on the upper left side and two lower pocket flaps. The buttons are silver colored, featuring traditional "Hap Arnold wings". Officer coats feature epaulets for the placement of rank. General officers wear a blue sleeve braid, while all other officers wear a blue sleeve braid. Like the Air Force, mirror-silver "U.S." insignia are worn on the collars, however Space Force guardians also wear a pair of U.S. Space Force lapel insignia. A silver name tag with blue detailing is worn on the right side of the uniform, while ribbons and occupational badges are worn on the left side of the uniform.


text: On 21 September 2021, John W. Raymond unveiled the prototypes of the Space Force's service uniform. It features a midnight blue jacket with six buttons on the right-hand side, platinum sleeve braids for commissioned officers, a midnight blue necktie that matches the jacket, platinum shirt, mirror-silver "U.S." insignia on the collars, dark grey pants, and black shoes. The new uniform is designed with women in mind to avoid the issues normally related to adapting them for women. The new uniforms will be issued for testing in the following months, before being distributed widely.


text: On 3 May 2022, John W. Raymond publicly wore the latest prototype of the service's dress uniform as he testified before a Senate Armed Services Committee hearing to review the Air Force's Defense Authorization Request for fiscal year 2023. Noteworthy changes from the prototype unveiled in September 2021 included: the addition of stripes down the tailored pants, the change of the pocket style, the addition of pockets on the lower half of the jacket, and the decrease of the number of buttons on the interior enclosure of the jacket.


text: On 17 January 2020, the Space Force announced that its combat utility uniform would be the same Operational Camouflage Pattern (OCP) uniform as when it was Air Force Space Command. The full-color United States flag is worn on the left side of the uniform. The name tape, branch tape, and rank are embroidered in space blue, distinguishing it from the OCP uniforms worn by the Army and Air Force (the Army uses black thread for embroidery and wears the full-color flag on the right arm, except in combat areas where a subdued black flag is used). The Air Force uses spice brown embroidery thread and wears a subdued spice brown flag on the right arm of the uniform at all times.) The OCP uniform was first introduced by the Army in 2015 and adopted by the Air Force in 2019.


text: The Space Force also authorized the Airman Battle Uniform as a combat utility uniform, which was introduced by the Air Force in 2007 and was phased out in April 2021.


text: Space Force cadets at the United States Air Force Academy wear the standard parade dress uniform with a platinum sash for graduation. Air Force cadets wear the same uniform, but with a gold sash.


title: Jeffrey Lurie

text: Jeffrey Robert Lurie (born September 8, 1951) is an American motion picture producer, businessman, and the owner of the Philadelphia Eagles of the National Football League (NFL).


title: Jeffrey Lurie

text: Lurie was born to a Jewish family in Boston, the son of Nancy (née Smith) and Morris John Lurie. His grandfather, Philip Smith, founded the General Cinema movie theater chain, which was one of the largest operators of drive-in movie theaters in the United States. His uncle is Richard A. Smith. He has two siblings, Peter and Cathy. His father died April 14, 1961, at the age of 44 when Jeffrey was nine years old.


title: Jeffrey Lurie

text: In the late 1960s, General Cinema began acquiring bottling franchises, including a Pepsi bottling operation. General Cinema evolved over the years into Harcourt General Inc., a $3.7-billion conglomerate based in Chestnut Hill, Massachusetts, with 23,700 employees worldwide. In its heyday it was the nation's fourth-largest chain of movie theaters, owned several publishing houses, three insurance companies, and a leading global consulting firm. In 1984 Carter Hawley Hale was acquired, which was at the time the tenth-largest clothing retailer in the United States, including Bergdorf Goodman and Neiman-Marcus.


title: Jeffrey Lurie

text: Lurie earned a B.A. from Clark University, a master's degree in psychology from Boston University, and a doctorate in social policy from The Heller School for Social Policy and Management at Brandeis University, where he wrote his thesis on the depiction of women in Hollywood movies. He was born to Jewish parents but has spent his adult life as a non-practicing Jew. Prior to entering business, Lurie served as an adjunct assistant professor of social policy at Boston University.


title: Jeffrey Lurie

text: In 1983, he left academia to join General Cinema Corporation, a major film company founded by his grandfather, Philip Smith, and headed by his uncle, Richard A. Smith. He worked as an executive in the company as a liaison between General Cinema Corporation and the production community in Hollywood. He was also an advisor in The General Cinema national film buying office.


title: Jeffrey Lurie

text: He then founded Chestnut Hill Productions in 1985, which produced a string of Hollywood movies and TV shows. The company initially started off with a multi-feature joint venture with Tri-Star Pictures to develop projects, then in 1987, three of the Chestnut Hill projects were picked up by MGM/UA Communications Co., two with Paramount Pictures and Warner Bros. Pictures each, and a single picture Chestnut Hill is producing for Universal Pictures, and a majority of the eight Chestnut Hill productions would be received by Tri-Star Pictures which then become an independent production company. Tri-Star Pictures received first look at all projects that were handled by Chestnut Hill Productions, with Tri-Star and Chestnut Hill to co-finance development and Tri-Star could pick up the entire tab on production.


title: Jeffrey Lurie

text: On February 27, 2011, the Lurie-produced movie "Inside Job" won an Academy Award (Oscar) for best documentary film. The company also produced television commercials. Two years later he won a second Oscar when "Inocente", in which he was executive producer, won for Best Documentary Short Film.


title: Jeffrey Lurie

text: As a fan of all the Boston sports teams, Lurie went to games and put himself to sleep listening to the Boston Red Sox on his transistor radio. The Luries had been season-ticket holders since the New England Patriots franchise began in 1960, the year the American Football League was founded. Lurie cheered for Gino Cappelletti, Houston Antwine, and Babe Parilli. In 1993, Lurie tried to buy the New England Patriots, but he dropped out of the bidding at $150 million when his uncle Richard Smith nixed the purchase based on the financials.


title: Jeffrey Lurie

text: Lurie's name also had surfaced in sale talks regarding the Los Angeles Rams, and he was a potential investor in a bid for a Baltimore expansion team with Robert Tisch, who subsequently bought 50% of the New York Giants. Five months later, Smith agreed to let his nephew buy the Philadelphia Eagles. Lurie contacted Norman Braman, then owner of the Eagles. Lurie bought the Philadelphia Eagles on May 6, 1994, from Braman for $195 million. Lurie and his mother, Nancy Lurie Marks (the only daughter of Philip Smith) of Chestnut Hill, Massachusetts, borrowed $190 million from the Bank of Boston to buy the Eagles. To back the Bank of Boston loan, Lurie put up millions of dollars' worth of personal stock in Harcourt General and GC Companies Inc., as equity capital. Additionally, he and his mother pledged their stock in the family trust as collateral so Lurie could borrow the rest.


title: Jeffrey Lurie

text: On February 4, 2018, the Eagles defeated the Patriots to win Super Bowl LII by the score of 41–33, giving Lurie his first title as Eagles owner. The victory evened the score with New England, as the only other Lurie-era Super Bowl appearance was a 24–21 loss to the Patriots in Super Bowl XXXIX.


title: Jeffrey Lurie

text: In a pre-production meeting for "I Love You To Death", Lurie met Christina Weiss, a former actress who was working for his production company. In 1992, Lurie married Weiss in Gstaad, Switzerland. They had two children: a son Julian (b. 1995) and a daughter Milena (b.1993). In 2012, the couple announced that they were divorcing; the divorce was finalized in August 2012. She received a "sizeable" ownership interest in the Philadelphia Eagles as part of the divorce settlement. On May 4, 2013, he married Tina Lai.


The 2012 United States presidential election in Ohio took place on November 6, 2012, as part of the 2012 United States presidential election in which all 50 states plus the District of Columbia participated. Ohio voters chose 18 electors to represent them in the Electoral College via a popular vote pitting incumbent Democratic President Barack Obama and his running mate, Vice President Joe Biden, against Republican challenger and former Massachusetts Governor Mitt Romney and his running mate, Congressman Paul Ryan. This election continued Ohio's bellwether streak, as the state voted for the winner of the presidency in every election from 1964 to 2016.


title: 2012 United States presidential election in Ohio

text: President Obama won the popular vote in Ohio with 50.67% of the vote over Mitt Romney in second place at 47.69%, a Democratic victory margin of 2.98%. Obama's performance was a decline from 2008 when he won the state by a 4.57% margin over U.S. Senator John McCain, and he narrowly lost five counties that he won in 2008. However, he narrowly improved his margins in Cuyahoga County and Franklin County, home to the second largest city, Cleveland, and the state's capital and largest city, Columbus, respectively, allowing him to carry the state. Obama became the first Democrat to win the White House without Belmont County since 1892 and the first to win without neighboring Jefferson County since 1916.


text: As of 2022, this is the last time the Democratic presidential nominee won Ohio, as well as the last time Wood County, Ottawa County, Sandusky County, Erie County, Stark County, Portage County, Trumbull County, and Ashtabula County have voted Democratic. This is also the last time as of 2022 that Ohio voted to the left of any of the following states: Florida, Arizona, Georgia, or North Carolina.


text: The Democratic primary was held on March 6, 2012, the same day as the Republican primary. Incumbent President Barack Obama ran unopposed, and thus won all 151 of the state's delegates.


text: Ohio has 66 delegates to the Republican National Convention. Three party officials (also known as "superdelegates") are not bound by the primary result. Forty-eight delegates are generally awarded winner-take-all by Congressional district. Another 15 delegates are awarded to the candidate who gets an outright majority statewide, or are allocated proportionately among candidates winning at least 20% of the vote if no candidate wins a majority.


text: Despite an early lead in the vote count and having won most counties, Santorum's lead was reduced and overcome by Romney as Hamilton and Cuyahoga County results came in. Romney also won areas such as Akron, Youngstown, Dayton and Columbus. These and other highly populated counties would eventually go to Obama in November.


text: 1. In the six congressional districts where Rick Santorum submitted only a partial slate of district delegates and district alternates by the late December 2011 deadline, he will be automatically awarded only the number of delegates he submitted, assuming he wins the particular district. The Ohio Republican Party said on March 2, 2012, that the remaining delegates in such districts will be "considered unbound" until a panel composed of three members of the Ohio GOP's central committee decides which campaign (if any) is permitted to appoint such delegates.


text: 2. In three congressional districts (OH-6, OH-9 and OH-13), Rick Santorum did not make the district-specific portion of the ballot.


text: 3. In every district, each of the 6 candidates listed above appears on the "at-large" portion of the ballot. The results of the at-large ballot will determine the allocation of fifteen national convention delegates.


text: Ohio was considered a key battleground state throughout the general election campaign, and both Barack Obama and Mitt Romney campaigned extensively in the state.


text: Obama's victory in Ohio was enough to push him over the 270 electoral vote line allowing him to win the election. At first the Romney campaign contested the call, but conceded at about 1:00 A.M. Obama's victory in Ohio can be attributed to several factors. Obama only won 17 out of Ohio's 88 counties. However, those 17 counties combined account for 56.56% of the state's total population. Romney did do well in most rural areas of the state, particularly in western Ohio. Romney also won all but one county in the Appalachia region, becoming the first Republican since Richard Nixon’s 2,900-plus-county landslide in 1972 to carry Belmont, Jefferson and Monroe Counties, and losing only Athens County, home of Ohio University. He also managed to flip the swing counties of Lake and Tuscarawas. Romney also did well in the northern Columbus suburbs. For Romney, most of his wins came from smaller populated counties. Obama won by comfortable margins in Franklin, Hamilton, and Lucas counties, home to the cities of Columbus, Cincinnati, and Toledo, respectively. Obama's greatest support came from northeast Ohio, centered in Cuyahoga and Summit counties, home to the cities of Cleveland and Akron, respectively, the second and fourth largest cities in the state. The surrounding Cleveland–Akron–Canton metropolitan area and the Lake Erie shore went mostly to Obama, allowing him to carry the state as a whole by a fairly comfortable 2.98% margin.


text: In February 2013, nineteen cases of voter fraud were investigated in Hamilton County. Three individuals were charged with voter fraud the following month, with one individual alleged to have voted six times. These incidents would not have affected the outcome of the Ohio race as President Obama ultimately carried the state by 166,272 votes.


text: Some experts believe that the popularity of the auto industry bailout put in place under President Obama helped him take the state.


title: Scott Valentine (actor)

text: Scott Eugene Valentine (born June 3, 1958) is an American actor, best known for his role as Nick Moore on the series "Family Ties".


title: Scott Valentine (actor)

text: Valentine was born in Saratoga Springs, New York, the son of Beverly Ann (née Hanna) and Edward Eugene Valentine. He began to pursue acting one year into his college education, attending the American Academy of Dramatic Arts in New York City. He completed the three-year program in one and a half years. He got as far as a screen test for the film "The Lords of Discipline" when he was hit, run over, and dragged by a truck on September 17, 1981 and his career was halted for three years as he recovered. He moved to Los Angeles and landed a recurring role on the TV series "Family Ties" as Nick Moore, the loveable but dim-witted boyfriend of Mallory Keaton from 1985 to 1989, for seasons 4 through 7.


title: Scott Valentine (actor)

text: During an interview for Montreal radio station CJAD, Valentine thought the role was not challenging enough for the money he was receiving, saying: "I'm so glad I went to the American Academy of Dramatic Arts and to all the other fine acting institutions so I could grunt on primetime television. The primal dig, the date from hell. It was a lot of fun, but literally there were times where I only had to utter two guttural utterances in a show and they paid me a bundle of cash for it. I felt bad at times."


title: Scott Valentine (actor)

text: Valentine's success as Nick Moore on "Family Ties" led to three separate spin-offs. The first starred Valentine and actor Herschel Bernardi called "Taking It Home". Filming was canceled when Bernardi died in 1986. The second spin-off placed Valentine's character in a "Friends"-like environment in New York City. The third was a pilot episode for a spin-off titled "The Art of Being Nick"; the episode aired once and co-starred Julia Louis-Dreyfus. "It came in number two and they still didn't pick it up," recalled Valentine.


title: Scott Valentine (actor)

text: He has appeared since then as a guest actor in several hit television series such as "", "NewsRadio", and "JAG"; his first major motion picture, "My Demon Lover"; and numerous TV and straight-to-video movies. He also voiced The Phantom in "Phantom 2040". He portrayed Metallo in an episode of "" TV series.


title: Scott Valentine (actor)

text: On September 29, 1985, in Los Angeles, Valentine married actress Kym Denyse (Fisher) Stephenson. Valentine and Stephenson divorced February 14, 2012. Valentine has four sons from the marriage; Trevin John (1986), Shayler Stephenson (1988), Jesstin Jay-Owen (1992) and Caden Edward (1998).


title: Scott Valentine (actor)

text: On November 7, 2021 Valentine married Jennifer Wood (née Malchow), another Saratoga Springs native, in their hometown of Saratoga Springs.


title: Scott Valentine (actor)

text: Valentine is a partner in Excelsior Capital Partners, a boutique investment firm that focuses on the renewable and sustainable energy sector.


title: Warner Bros. Studios, Leavesden

text: Warner Bros. Studios, Leavesden is an studio complex in Leavesden in Watford, Hertfordshire, in South East England. Formerly known as Leavesden Film Studios and still colloquially known as Leavesden Studios or simply Leavesden, it is a film and media complex owned by Warner Bros. The studios were all converted from an aircraft factory and airfield called Leavesden Aerodrome, a centre of British aircraft production during World War II. The nearest railway station is King's Langley which is a walking distance of .


title: Warner Bros. Studios, Leavesden

text: Warner Bros. Studios, Leavesden is one of only a few places in the UK where large-scale film productions can be made. The studios contain approximately of flexible space which includes stage space, one of the largest filtered and heated stage-based water tanks in Europe, production office space, workshops and support buildings, along with an extensive backlot which offers a 180-degree uninterrupted horizon, favourable for exterior sets. Following an over £110 million refurbishment by Warner Bros., the studios are now one of the largest and most state-of-the-art secure filmmaking facilities in the world.


title: Warner Bros. Studios, Leavesden

text: Though the studios are owned by Warner Bros., all of the studio facilities are available to rent for any production. Since acquiring the site, Warner Bros. has opened a public attraction named Warner Bros. Studio Tour London – The Making of "Harry Potter", which receives over 6,000 visitors a day at peak times. The site maintains a secure studio space within the same complex.


title: Warner Bros. Studios, Leavesden

text: Leavesden Aerodrome was a British airfield created in 1940 by the de Havilland Aircraft Company and the Air Ministry in the village of Leavesden, between Watford and Abbots Langley, in Hertfordshire.


title: Warner Bros. Studios, Leavesden

text: Construction began in 1940 after the outbreak of World War II. The de Havilland company, who were based in nearby Hatfield, entered into a contract with the Air Ministry to produce what would become known as the Mosquito fast bomber aircraft. Space for the large scale hangars needed to produce the huge number of aeroplanes required was not available at de Havilland's Hatfield Aerodrome. So the Ministry of Supply requisitioned this new site in Leavesden, which was an empty plot of land at the time from the Watford Corporation, and it was developed into the complex that it is today. The construction was enormously expensive so parts of the site were leased to the London Aircraft Production Group and The Second Aircraft Group. Under Handley Page, another Hertfordshire-based aeroplane manufacturer contracted to the Air Ministry, these groups produced the Handley Page Halifax heavy bomber. As a result, by the end of the war Leavesden Airfield was, by volume, the largest factory in the world.


title: Warner Bros. Studios, Leavesden

text: The two planes were both critical successes for Britain during the conflict. Due to the high priority placed on aircraft production, large numbers of workers were drafted with little experience or training in aircraft production, with over half the workforce eventually being female. As part of constructing the aircraft factory an airstrip was created, first so the planes could be tested and later to deliver the craft to their final destinations. The runway and control tower still remain to this day, even after two major renovations, in an effort to preserve the site's history. The runway is now the main road through the complex and the tower is currently an observation lounge.


title: Warner Bros. Studios, Leavesden

text: After the war, the aerodrome was purchased outright by de Havilland, who themselves had a succession of owners in the following decades, including Hawker Siddeley from 1959, but ultimately they and the site were acquired by Rolls-Royce who continued production and design of helicopter engines. Under Rolls-Royce ownership the RTM322 engine for the UK Apache, Merlin and NH90 helicopters was designed, developed and produced at Leavesden as a joint venture with Turbomeca of France. The airfield was also used by commercial small business aircraft as the field is close to both the M1 and M25 motorways. However, by the early 1990s, Britain's manufacturing industry was in decline and Rolls-Royce had sold their interests in the site and transferred all work to their Bristol facility. Unable to find a new owner, by 1994 Leavesden Aerodrome was left disused and all but abandoned.


title: Warner Bros. Studios, Leavesden

text: In 1994, Eon Productions' "James Bond" film "GoldenEye" was to be the next film in the series. Pinewood Studios, their traditional home studio, was fully booked with other productions, not being prepared for the series' unexpected return (production had been delayed for several years thanks to legal issues between MGM and Eon Productions). Facing little time to find a space in which they could build the number of large scale sets required, the production discovered the unoccupied Leavesden. The wide, tall and open aircraft hangars were uniquely well suited to conversion into film stages. Eon leased the site for the duration of their shoot and went about gutting the factories, turning them into stages, workshops and offices – in short a working film studio. This process is shown on the 2006 DVD's special features. Members of the production crew, impressed by the enormous size of the filmmaking complex they suddenly had to themselves, jokingly called Leavesden ""Cubbywood"" after Eon's long serving producer Albert R. 'Cubby' Broccoli.


title: Warner Bros. Studios, Leavesden

text: Leavesden Studios, as the site was rebranded by its owners, quickly became popular after filming of "GoldenEye" was completed. A succession of major feature films made use of the site, in 1997, the first of the "Star Wars" prequels, "" and later Tim Burton's "Sleepy Hollow".


title: Warner Bros. Studios, Leavesden

text: By the year 2000, Heyday Films had acquired use of the site on behalf of Warner Bros. for what would be the first in a series of films, "Harry Potter and the Philosopher's Stone". Every one of the "Harry Potter" films was based at Leavesden Studios over the following ten years.


title: Warner Bros. Studios, Leavesden

text: While other productions—almost exclusively other Warner Bros. productions—made partial use of the studios, the site was mostly occupied by "Harry Potter"s permanent standing sets. Indeed, some films, such as "" and "Sherlock Holmes" actually made use of some of the "Harry Potter" sets since they were sufficiently appropriate for their Victorian setting and tone. During this time, however, it was noted that there were some ways in which the site's facilities might be improved. None of the stages were adequately soundproofed and the WW2 era ceilings had a tendency to leak during rainy weather.


title: Warner Bros. Studios, Leavesden

text: One of the more noticeable exterior sets constructed on the Leavesden backlot (outdoors) was a row of ten houses (five per side) along a street, which was created for the "Harry Potter" series to represent Privet Drive.


title: Warner Bros. Studios, Leavesden

text: On 21 March 2010, there was a fire on one of the Hogwarts sets during filming of "Harry Potter and the Deathly Hallows – Part 2" at Leavesden Studios. Not much of the set was badly damaged.


title: Warner Bros. Studios, Leavesden

text: In 2010, as the final "Harry Potter" film was nearing completion, Warner Bros. announced their intention to purchase the studio as a permanent European base, the first studio to do so since Metro-Goldwyn-Mayer in the 1940s.


title: Warner Bros. Studios, Leavesden

text: By November 2010, Warner Bros. completed its purchase of Leavesden Studios and announced plans to invest more than £100 million into the site they had occupied for over ten years, rebranding it Warner Bros. Studios, Leavesden. The studios make Warner Bros. the only Hollywood film studio with a permanent base in the United Kingdom.


title: Warner Bros. Studios, Leavesden

text: Much of the redevelopment involved converting stages A to H into sound stages and equipping all the facilities with the latest fittings a production might require. The refurbished stages were conversions of the original buildings and the runway and control tower from the site's days as an aerodrome remain intact as well as all of the buildings' original structures. The full scale refurbishment and renovation of the production facilities were completed and the studios reopened to film and television work in 2012.


title: Warner Bros. Studios, Leavesden

text: As part of this redevelopment Warner Bros. also created two entirely new soundstages, J & K, to house a permanent public exhibition named the Warner Bros. Studio Tour London – The Making of "Harry Potter", creating 300 new jobs in the local area. Currently the whole attraction is dedicated to the making of "Harry Potter" and is now home to many of the series' sets, props and costumes. It was opened to the public in early 2012.


title: Warner Bros. Studios, Leavesden

text: The first film to start shooting at the newly refurbished studios was "Edge of Tomorrow". Though the studios are privately owned, the shooting spaces are available to rent for any production.


title: Warner Bros. Studios, Leavesden

text: On 30 June 2014, Warner Bros. announced the expansion of the studio, building three new state-of-the-art stages and adding a further of office space. The announcements were made after a reception celebrating the Creative Industries, hosted by Prime Minister David Cameron, and attended by WB's CEO Kevin Tsujihara and WB UK's MD Josh Berger. Leavesden's trio of new sound-stages consist of one building and two buildings, along with of adjacent office space which were completed by the end of 2014. On the same day the filming of live-action "The Legend of Tarzan" got underway at the studio. Following the refurbishments, the studios are now one of the largest and most state-of-the-art secure filmmaking facilities in the world.


title: Warner Bros. Studios, Leavesden

text: Almost twenty years after the complex was converted from aerodrome to film studios—and over a year since the completion of work on the newly refurbished studios—the site was officially opened by the Duke and Duchess of Cambridge on 26 April 2013. On their visit, they were accompanied by the Duke's brother Prince Harry and J. K. Rowling (who had been unable to attend the tour's grand opening the year before), amongst other guests. Several hundred beneficiaries of supported charities were given invitations to the Studio Tour on the day of the visit. The royal entourage visited both the tour and the studios, viewing the props and costumes from Christopher Nolan's "Batman" films, before conducting the site's inauguration.


title: Warner Bros. Studios, Leavesden

text: On 10 July 2019, a fire broke out in one of the studio's sets, and would take responders 15 hours to extinguish. A set for the HBO television series "Avenue 5" was damaged in the fire.


title: Warner Bros. Studios, Leavesden

text: The studios have also been used for various music videos and television commercials, most notably support for the video for Jamiroquai's "Deeper Underground".


title: Warner Bros. Studios, Leavesden

text: Warner Bros. Studio Tour London – The Making of "Harry Potter" is a public attraction in Leavesden Hertfordshire, England. It is a permanent behind-the-scenes exhibition of the "Harry Potter" films.


title: Warner Bros. Studios, Leavesden

text: The Studio Tour, opened to the public in early 2012. The grand opening event was attended by many of the "Harry Potter" film series cast and crew members.


title: Warner Bros. Studios, Leavesden

text: Each tour session typically lasting three hours, the studio tour has the capacity to handle 6,000 visitors daily. Despite Warner Bros. being the studio behind "Harry Potter", the tour is not styled as a theme park, due to the fact that Warner Bros. sold the licence to do so to Universal Studios.


title: Warner Bros. Studios, Leavesden

text: As early as 2001, after the success of the first film, Warner Bros. planned to build an attraction dedicated to the series in place and so began storing items from the films when they were no longer being used.


title: Warner Bros. Studios, Leavesden

text: The tour's layout and overall presentation was designed by the Los Angeles-based Thinkwell Group in close collaboration with Warner Bros. and the actual filmmakers, including Production Designer Stuart Craig, Set Dresser Stephenie McMillan, Creature Designer Nick Dudman and Special Effects Supervisor John Richardson. It only includes sets, props and costumes that were actually created for or used in the production of the "Harry Potter" film series. Sets like the Great Hall, Dumbledore's Office, Diagon Alley, the Ministry of Magic, Gryffindor Common Room and Boys' Dormitory, Hagrid's Hut and a 1:24 scale model of Hogwarts Castle.


title: Warner Bros. Studios, Leavesden

text: Since opening in 2012, TripAdvisor has reported "The Making of Harry Potter" as the highest-rated attraction in the world every year since.


title: Warner Bros. Studios, Leavesden

text: Warner Bros. has continued to put on special features for the school holidays, such as Dark Arts and Animal Actors. Some installations like the Wand Choreography Interactive and the inside of the last No. 4 Privet Drive Exterior set have been so popular that they have remained after their respective features have closed.


title: Warner Bros. Studios, Leavesden

text: In January 2015, the attraction's first expansion was announced – a new "Platform 9¾" section, where visitors are able to board the original carriages behind the Hogwarts Express steam engine used in the films. The setup includes the locomotive GWR 4900 Class 5972 "Olton Hall" (dressed as 5972 "Hogwarts Express") and the British Rail Mark 1 train that appeared in the films, brought to life by John Richardson's special effects team. Finally a new green screen experience illustrates what working on the films is like from an actor's point of view. This section opened in late March 2015.


title: Warner Bros. Studios, Leavesden

text: The tour in Warner Bros. Studios, Burbank has been renamed Warner Bros. Studio Tour Hollywood (previously it was known as the Warner Bros. Studios VIP Tour). Warner has altered the tour, offering more facilities and options to visitors.


title: Flag of Tennessee

text: The flag of Tennessee displays an emblem on a field of red, with a strip of blue bordered by white on the fly. The emblem in the middle consists of three stars on a blue circle also with a white border. The central emblem portion of the flag has been adopted as the state's unofficial logo, and appears in the logos of some Tennessee-based companies and sports teams. Examples include the First Horizon Bank and the Tennessee Titans.


title: Flag of Tennessee

text: In 2001, the North American Vexillological Association surveyed its members on the designs of the 72 U.S. state, territorial, and Canadian provincial flags and ranked the Tennessee flag 14th.


title: Flag of Tennessee

text: In 1897 the state adopted a red, white, and blue tricolor. The three bars were deliberately slanted in an effort to represent the geographically distinct regions of Tennessee. The flag included the number "16," Tennessee having been admitted as the 16th state of the Union, and the words "The Volunteer State", the state's official nickname.


title: Flag of Tennessee

text: The current flag was designed by Colonel Le Roy Reeves, a Johnson City attorney who was then serving in the Tennessee National Guard. The Tennessee General Assembly officially adopted the flag on April 17, 1905.


title: Flag of Tennessee

text: The stars represent the three geographically and legally distinct "Grand Divisions" of Tennessee (i.e. East Tennessee, Middle Tennessee, and West Tennessee). The blue circle around the stars represents the unity of those grand divisions. The blue bar at the edge of the flag was just a design consideration. When asked about the blue bar, Colonel Reeves stated "The final blue bar relieves the sameness of the crimson field and prevents the flag from showing too much crimson when hanging limp." In October 1917, "National Geographic" erroneously reported the stars represented the state as the third to enter the Union after the original thirteen.


title: Flag of Tennessee

text: Vexillologist Steven A. Knowlton believes that "the Tennessee flag has pragmatic unity with the Confederate flag: both share the element of white stars inside a fimbriated blue charge, and the element of that blue charge on a red field." He also notes the resemblance between the Tennessee State Flag and . However, Knowlton also acknowledged that there is no direct evidence of the flag being designed to emulate the Confederate flag.


title: Flag of Tennessee

text: In 1976, the U.S. Postal Service issued a sheet of 13 cent stamps illustrating U.S. state flags. Tennessee's was illustrated upside down.


title: Flag of Tennessee

text: Alongside the state flag, there are other flags used by the government of Tennessee. The flag for the Governor of Tennessee (shown at right) has been in use since 1939. It is a scarlet flag, with four stars, one in each corner, and the State Military Crest, a tree with three white stars, in the center. The Tennessee General Assembly has its own flag as well.


title: Frank–Starling law

text: The Frank–Starling law of the heart (also known as Starling's law and the Frank–Starling mechanism) represents the relationship between stroke volume and end diastolic volume. The law states that the stroke volume of the heart increases in response to an increase in the volume of blood in the ventricles, before contraction (the end diastolic volume), when all other factors remain constant. As a larger volume of blood flows into the ventricle, the blood stretches cardiac muscle, leading to an increase in the force of contraction. The Frank-Starling mechanism allows the cardiac output to be synchronized with the venous return, arterial blood supply and humoral length, without depending upon external regulation to make alterations. The physiological importance of the mechanism lies mainly in maintaining left and right ventricular output equality.


title: Frank–Starling law

text: The Frank-Starling mechanism occurs as the result of the length-tension relationship observed in striated muscle, including for example skeletal muscles, arthropod muscle and cardiac (heart) muscle. As striated muscle is stretched, active tension is created by altering the overlap of thick and thin filaments. The greatest isometric active tension is developed when a muscle is at its optimal length. In most relaxed skeletal muscle fibers, passive elastic properties maintain the muscle fibers length near optimal, as determined usually by the fixed distance between the attachment points of tendons to the bones (or the exoskeleton of arthropods) at either end of the muscle. In contrast, the relaxed sarcomere length of cardiac muscle cells, in a resting ventricle, is lower than the optimal length for contraction. There is no bone to fix sarcomere length in the heart (of any animal) so sarcomere length is very variable and depends directly upon blood filling and thereby expanding the heart chambers. In the human heart, maximal force is generated with an initial sarcomere length of 2.2 micrometers, a length which is rarely exceeded in a normal heart. Initial lengths larger or smaller than this optimal value will decrease the force the muscle can achieve. For longer sarcomere lengths, this is the result of there being less overlap of the thin and thick filaments; for shorter sarcomere lengths, the cause is the decreased sensitivity for calcium by the myofilaments. An increase in filling of the ventricle increases the load experienced by each cardiac muscle cells, stretching their sarcomeres toward their optimal length.


title: Frank–Starling law

text: The stretching sarcomeres augments cardiac muscle contraction by increasing the calcium sensitivity of the myofibrils, causing a greater number of actin-myosin cross-bridges to form within the muscle. Specifically, the sensitivity of troponin for binding Ca increases and there is an increased release of Ca from the sarcoplasmic reticulum. In addition, stretch of cardiac myocytes increases the releasability of Ca from the internal store, the sarcoplasmic reticulum, as shown by an increase in Ca spark rate upon axial stretch of single cardiac myocytes. Finally, there is thought to be a decrease in the spacing between thick and thin filaments, when a cardiac muscle is stretched, allowing an increased number of cross-bridges to form. The force that any single cardiac muscle cell generates is related to the sarcomere length at the time of muscle cell activation by calcium. The stretch on the individual cell, caused by ventricular filling, determines the sarcomere length of the fibres. Therefore the force (pressure) generated by the cardiac muscle fibres is related to the end-diastolic volume of the left and right ventricles as determined by complexities of the force-sarcomere length relationship.


title: Frank–Starling law

text: Due to the intrinsic property of myocardium that is responsible for the Frank-Starling mechanism, the heart can automatically accommodate an increase in venous return, at any heart rate. The mechanism is of functional importance because it serves to adapt left ventricular output to right ventricular output. If this mechanism did not exist and the right and left cardiac outputs were not equivalent, blood would accumulate in the pulmonary circulation (were the right ventricle producing more output than the left) or the systemic circulation (were the left ventricle producing more output than the right).


title: Frank–Starling law

text: Premature ventricular contraction causes early emptying of the left ventricle (LV) into the aorta. Since the next ventricular contraction occurs at its regular time, the filling time for the LV increases, causing an increased LV end-diastolic volume. Due to the Frank–Starling mechanism, the next ventricular contraction is more forceful, leading to the ejection of the larger than normal volume of blood, and bringing the LV end-systolic volume back to baseline.


title: Frank–Starling law

text: Diastolic dysfunction is associated with a reduced compliance, or increased stiffness, of the ventricle wall. This reduced compliance results in an inadequate filling of the ventricle and a decrease in the end-diastolic volume. The decreased end-diastolic volume then leads to a reduction in stroke volume because of the Frank-Starling mechanism.


title: Frank–Starling law

text: The Frank–Starling law is named after the two physiologists, Otto Frank and Ernest Henry Starling. However, neither Frank nor Starling was the first to describe the relationship between the end-diastolic volume and the regulation of cardiac output. The first formulation of the law was theorized by the Italian physiologist Dario Maestrini, who on December 13, 1914, started the first of 19 experiments that led him to formulate the ""legge del cuore" ".


title: Frank–Starling law

text: Otto Frank's contributions are derived from his 1895 experiments on frog hearts. In order to relate the work of the heart to skeletal muscle mechanics, Frank observed changes in diastolic pressure with varying volumes of the frog ventricle. His data was analyzed on a pressure-volume diagram, which resulted in his description of peak isovolumic pressure and its effects on ventricular volume.


title: Frank–Starling law

text: Starling experimented on intact mammalian hearts, such as from dogs, to understand why variations in arterial pressure, heart rate, and temperature do not affect the relatively constant cardiac output. More than 30 years before the development of the sliding filament model of muscle contraction and the understanding of the relationship between active tension and sarcomere length, Starling hypothesized in 1914, "the mechanical energy set free in the passage from the resting to the active state is a function of the length of the fiber." Starling used a volume-pressure diagram to construct a length-tension diagram from his data. Starling's data and associated diagrams, provided evidence that the length of the muscle fibers, and resulting tension, altered the systolic pressure.


title: Carbondale, Illinois

text: Carbondale is a city in Jackson and Williamson Counties, Illinois, United States, within the Southern Illinois region informally known as "Little Egypt". The city developed from 1853 because of the stimulation of railroad construction into the area. Today the major roadways of Illinois Route 13 and U.S. Route 51 intersect in the city. The city is southeast of St. Louis, on the northern edge of the Shawnee National Forest. Carbondale is the home of the main campus of Southern Illinois University (SIU).


title: Carbondale, Illinois

text: As of the 2020 census, the city had a population of 25,083, making it the most populous city in Southern Illinois outside the St. Louis Metro-East region.


title: Carbondale, Illinois

text: In August 1853, Daniel Harmon Brush, John Asgill Conner, and Dr. William Richart bought a parcel of land between two proposed railroad station sites (Makanda and De Soto) and two county seats (Murphysboro and Marion). Brush named Carbondale for the large deposit of coal in the area. The first train through Carbondale arrived on Independence Day 1854, traveling north on the main line from Cairo, Illinois.


title: Carbondale, Illinois

text: By the time of the American Civil War, Carbondale had developed as a regional center for transportation and business, surrounded by agricultural development. This part of Illinois was known as "Little Egypt" because of the confluence of the Ohio and Mississippi rivers, where the town of Cairo is located.


title: Carbondale, Illinois

text: The city has had a college since 1856 beginning with the Presbyterian-founded Carbondale College which was later converted to an elementary school. Carbondale also won the bid for the new state teacher training school for the region, and Southern Illinois Normal University opened in 1874. This gave the town new industry, new citizens, and a supplement to public schools. In 1947, the name was changed to Southern Illinois University (SIU). It has become the flagship of the Southern Illinois University system. This institution, now recognized as a national research university, has nearly 18,000 students enrolled (as of 2014) and offers a wide variety of undergraduate and graduate specialties.


title: Carbondale, Illinois

text: On April 29, 1866, one of the first formal Memorial Day observations following the Civil War was held at the city's Woodlawn Cemetery. Local resident, General John A. Logan, gave the principal address. Logan, as co-founder of the Civil War veteran's group the "Grand Army of the Republic", issued General Order #11 on March 3, 1868, calling for a national day of remembrance for Civil War dead. This order served as the basis for the creation of a formal Memorial Day. Logan called observance day "Decoration Day" and proposed it for May 30, to assure flowers would be in bloom nationwide.


title: Carbondale, Illinois

text: In the early 20th century, Carbondale was known as the "Athens of Egypt," due to the expansion of the college and university, and the region's moniker of "Little Egypt." The phrase dates to at least 1903, when it appeared in a local paper. By 1922, the "Carbondale Free Press" was using the phrase on its flag.


title: Carbondale, Illinois

text: On November 12, 1970, a largescale shootout occurred between local police and members of the local chapter of the Black Panther Party who were meeting at a house in town. The event was later chronicled in the documentary "778 Bullets", made by a professor at SIU.


title: Carbondale, Illinois

text: The area was in totality during the solar eclipse of August 21, 2017, with Giant City State Park, just south of the city, experiencing the longest period of totality during the eclipse (approximately 2 minutes and 40 seconds), earning it the nickname, "Eclipse Crossroads of America". It will also be within the path of totality of the solar eclipse of April 8, 2024, making it one of only a handful of cities within the direct paths of both eclipses.


title: Carbondale, Illinois

text: Carbondale is located at (37.726, −89.220). It is in the watershed of the Big Muddy River, at above sea level. Carbondale has been in totality path of one previous solar eclipse on August 21, 2017 and hosted the longest duration of totality with 2 minutes 41.6 seconds just to its south in Makanda Township, and additionally will be in the path of another April 8, 2024.


title: Carbondale, Illinois

text: According to the 2010 census, Carbondale has a total area of , of which (or 97.55%) is land and (or 2.45%) is water.


title: Carbondale, Illinois

text: Carbondale lies in the northern limits of a humid subtropical climate (Köppen "Cfa"), with four distinct seasons. The monthly daily average temperature ranges from in January to in July. On average, there are 38 days of + highs, 16 days where the high fails to rise above freezing, and 1.6 nights of sub- per year. It has an average annual precipitation of , including an average of snow. Extremes in temperature range from on January 11, 1977 up to on August 9, 1930.


title: Carbondale, Illinois

text: Carbondale receives thunderstorms on an average of 50 days per year. Particularly in the spring, these storms can often be severe, with high winds, damaging hail, and tornadoes.


title: Carbondale, Illinois

text: As of the census of 2000, there were 25,597 people, 10,018 households, and 3,493 families residing in the city. The population density was . There were 11,005 housing units at an average density of . The racial makeup of the city was 66.08% White, 23.14% Black or African American, 0.22% Native American, 6.67% Asian, 0.08% Pacific Islander, 1.42% from other races, and 2.40% from two or more races. Hispanic or Latino of any race were 3.05% of the population.


title: Carbondale, Illinois

text: There were 9,981 households, out of which 17.0% had children under the age of 18 living with them, 22.1% were married couples living together, 10.1% had a female householder with no husband present, and 21.5% were non-families. 43.5% of all households were made up of individuals, and 6.9% had someone living alone who was 65 years of age or older. The average household size was 2.33 and the average family size was 2.78.


title: Carbondale, Illinois

text: In the city, the population was spread out, with 15.8% under the age of 18, 35.4% from 18 to 24, 27.1% from 25 to 44, 12.5% from 45 to 64, and 9.3% who were 65 years of age or older. The median age was 25 years. For every 100 females, there were 106.2 males. For every 100 females age 18 and over, there were 105.6 males.


title: Carbondale, Illinois

text: The median income for a household in the city was $27,882, and the median income for a family was $34,601. Males had a median income of $30,217 versus $24,114 for females. The per capita income for the city was $13,346. About 13.5% of families and 21.4% of the population were below the poverty line, including 32.1% of those under the age of 18 and 13.2% of those 65 and older. However, traditional measures of income and poverty can be misleading when applied to cities with high student populations, such as Carbondale.


title: Carbondale, Illinois

text: The city of Carbondale has a council-manager government. There are a total of seven elected city officials: a mayor and six city council members elected at-large for four-year staggered terms. The City Manager, a professional hired by the city council, appoints the department heads. The city provides services such as police, fire, development services, public works, and public library. Several boards and commissions allow for citizen participation, bringing more citizens into civic activities and helping to bridge the gap between the residents and the government. Carbondale is a zoned, home rule municipality. In 2010, the city approved a new comprehensive plan that lays out goals for the future and ways to accomplish these goals.


title: Carbondale, Illinois

text: On April 5, 2011, Joel Fritzler was elected mayor for a four-year term, but on February 3, 2014, he resigned to accept a job in Arizona. The City Council chose Don Monty as acting mayor to finish Fritzler's term. On April 7, 2015, John "Mike" Henry was elected mayor, and he took office in May 2015.


title: Carbondale, Illinois

text: In addition to Southern Illinois University, which presents regular concerts and theatrical productions, as well as art and history exhibits, the city has a variety of unique cultural institutions. PBS and NPR broadcasting stations (WSIU) are affiliated with the university. Carbondale also is home to WDBX Community Radio for Southern Illinois, and the Big Muddy Independent Media Center.


title: Carbondale, Illinois

text: The area is served by a regional daily newspaper, "The Southern Illinoisan" and the university's "Daily Egyptian", as well as two weeklies, the "Carbondale Times" and the "Nightlife."


title: Carbondale, Illinois

text: SIU has a teaching museum on campus, the University Museum, which has 60,000 artifacts in its collection and hosts traveling shows from known artists. In addition to the University Museum, there is the African American Museum and The Science Center. Theater-goers can see both professional and student-produced plays and performances at the university's McLeod and Kleinau Theaters. SIUC is also home to the largest auditorium in Southern Illinois, Shryock Auditorium. Shryock Auditorium has brought in many performing artists, such as B.B. King, the Supremes, Ray Charles, and Judy Collins, along with orchestras and other musical productions. Carbondale is also home to Lost Cross, the longest running DIY punk venue in the country, which has hosted local and national acts like Black Flag.


title: Carbondale, Illinois

text: Theater-goers can also attend off-campus productions by The Jackson County Stage Company (Stage Company). In 2007, the Stage Company and Carbondale Community Arts (CCA) partnered to purchase and renovate the Varsity Theater, which had been vacant since 2003, into the Varsity Center for the Arts (VCA). The VCA is now the performing home of the Stage Company and also supports a variety of other fine arts and performances through the CCA.


title: Carbondale, Illinois

text: Civic action is encouraged by groups such as Carbondale Conversations for Community Action (the local implementation of Study Circles). There are several lodges and clubs, such as the Fraternal Order of Eagles, Elks, Rotary International, and the A.F.A.M (Freemasonry).


title: Carbondale, Illinois

text: The Women's Center, in continuous service since its founding in 1972, was one of the first domestic violence shelters in the United States.


title: Carbondale, Illinois

text: Spirituality finds expression in Carbondale in churches of a variety of Christian denominations, a Unitarian Universalist fellowship, two mosques, a Jewish congregation, a Sufi community, and two Buddhist organizations – the Shawnee Dharma Group and the Sunyata Center. The first Hindu temple in Southern Illinois held its grand opening in Carbondale in June 2013. The Gaia House Interfaith Center provides space for intercultural exchange and personal growth. It is also an education center to help the community become more ecologically conscious, understand how to incorporate better practices into daily life, and set goals for the future.


title: Carbondale, Illinois

text: Notable poets from Carbondale include Rodney Jones, Judy Jordan, Allison Joseph, and the Transpoetic Playground collective.


title: Carbondale, Illinois

text: The city's business districts include several large shopping malls (including University Mall on the east side of town), featuring a mixture of national chain stores and locally owned businesses. In addition, Carbondale is home to many small shops and restaurants, many of them located in the downtown area. The downtown district is supported by Carbondale Main Street, which has listings and information about individual businesses. Because of the large student population in the city, there is a great variety of restaurants, featuring many nationalities of cuisine. Several bars and coffeehouses offer live music, poetry readings, and other entertainment. The Carbondale Chamber of Commerce offers information on local businesses in over 60 categories.


title: Carbondale, Illinois

text: Carbondale is known for a number of yearly festivals, including the Lights Fantastic parade in December, the Big Muddy Film Festival (February/March), the Southern Illinois Irish Festival (April), the Indian (Hindu, Sikh and Jain) celebration of Diwali (October/November), the Great Cardboard Boat Regatta (April), the Sunset Concerts (a summer series of free outdoor concerts on the Southern Illinois University campus and in city parks), and Brown Bag Concerts (a spring and fall series of free outdoor concerts in the Town Square Pavilion).


title: Carbondale, Illinois

text: Carbondale has 18 public tennis courts, as well as the Superblock, which is a sports multi-complex with baseball, softball, soccer, football, and track fields. The Carbondale Park District maintains seven parks and an indoor pool for public use. In 2010 the park district opened a new spray park in Crispus Attucks Park, and a water park opened in May 2016 at the Superblock. Southern Illinois University's Recreation Center is open to the public; it provides swimming, bowling, rock climbing walls, tennis, basketball, an indoor track, racquetball, weight training, and a variety of exercise equipment.


title: Carbondale, Illinois

text: Carbondale is located near many venues for outdoor activities, including some 14 parks in the immediate vicinity. These include the Crab Orchard National Wildlife Refuge, the Shawnee National Forest, Giant City State Park, Little Grand Canyon, Piney Creek Ravine, Pomona Natural Bridge, the Garden of the Gods Wilderness area, and Trail of Tears State Park. These areas offer opportunities for hiking, boating, biking, and horseback riding.


title: Carbondale, Illinois

text: Five minutes south of Carbondale is the city reservoir, Cedar Lake, which is open to kayaking and canoeing. The north access features several dramatic rock bluffs and secluded bays. Other lakes nearby include Little Grassy Lake, Devils Kitchen Lake, Crab Orchard Lake, and Kinkaid Lake. Another more remote location is Cache River Swamp, the northernmost cypress swamp in North America. The surrounding areas also offer hiking and mountain biking.


title: Carbondale, Illinois

text: Also a few minutes south of Carbondale is Jeremy Rochman Memorial Park, established by Barrett Rochman in memory of his son Jeremy "Boo" Rochman, who died in an auto accident at age 19. It features a castle with life-sized figures on a "Dungeons & Dragons" theme.


title: Carbondale, Illinois

text: The Shawnee National Forest, close to Carbondale, is home to many wineries. The Shawnee Hills Wine Trail visits twelve vineyards in scenic settings, offering local wines and dining facilities. Several of the vineyards are bed-and-breakfasts or offer cabins for close accommodations.


title: Carbondale, Illinois

text: The presence of Southern Illinois University also means that Carbondale area residents can attend Division I events of SIU's "Salukis" sport teams. The mascot term "Salukis" is a reference to a dog breed from ancient Egypt, a nod to the fact that the Southern Illinois region is frequently referred to by the nickname "Little Egypt."


title: Carbondale, Illinois

text: Due to the presence of Southern Illinois University, Carbondale residents have a tradition of political activism. During the Vietnam War, and especially after the Kent State shootings, massive anti-war demonstrations took place on the SIU campus and on the streets of Carbondale. They resulted in the closure of SIU, more than $100,000 of property damage, more than 400 arrests, and the deployment of the National Guard to restore order.


title: Carbondale, Illinois

text: In 2011, the Occupy Movement took up residence on the lawn of Quigley Hall at Southern Illinois University, occasionally clashing with local police and with university policy.


title: Carbondale, Illinois

text: SIU's Faculty Association went to the picket lines on November 3, 2011, after an agreement could not be reached between the Association and the administration concerning contracts. The other unions—the Non-Tenure Track Faculty Association, the Association of Civil Service Employees, and Graduate Assistants United—all settled with the administration within hours of the picketing action. The Faculty Association came to an agreement with the administration on November 10. The strike was the first ever in the school's history.


title: Carbondale, Illinois

text: Several local organizations are concerned with peace, justice and the environment, including the Peace Coalition of Southern Illinois/Fellowship of Reconciliation, the Shawnee Green Party, the Student Environmental Center, the Southern Illinois Center for a Sustainable Future, and local chapters of the American Civil Liberties Union, the Sierra Club, and the National Audubon Society.


title: Carbondale, Illinois

text: An area near campus known as "The Strip" was also the site of several infamous riots on Halloween in the 1980s and 1990s. The last Halloween riot occurred in 2000, when students clashed with and were tear gassed by police. Property and trees in the area of The Strip were destroyed. After the 2000 riot, measures were taken to prevent violence on Halloween weekend. The campus and the bars along Southern Illinois Avenue were closed on Halloween in following years.


title: Carbondale, Illinois

text: The city of Carbondale sits on the intersection of U.S. Route 51 and Illinois Route 13. Interstate 57 is accessible to the east on Route 13 at Marion, and to the south on Rt. 51 near Dongola. Interstate 64 is accessible to the north on Rt. 51. Interstate 24 is accessible six miles south of Marion on I-57. The city is 331 highway miles from Chicago, 96 highway miles from St. Louis, and 213 highway miles from Memphis. (A historical note: When Illinois first developed the state highway system in the 1920s, what is now Rt. 51 was Illinois Route 2, which ran the length of the state).


title: Carbondale, Illinois

text: The city is twelve miles (19 km) away from the Williamson County Regional Airport, where Cape Air provides passenger service to St. Louis and Nashville. The Southern Illinois Airport is located northwest of the city and offers private aviation services and is home to SIU's aviation program. On April 2, 2010, state and university officials broke ground on a Transportation Education Center on the airport grounds.


title: Carbondale, Illinois

text: Amtrak Train 59, the southbound "City of New Orleans", departs Carbondale daily with service to Memphis, Jackson, and New Orleans (and intermediate stations). Amtrak Train 58, the northbound City of New Orleans, departs Carbondale daily with service to Centralia, Effingham, Mattoon, Champaign-Urbana, Kankakee, Homewood, and Chicago.


title: Carbondale, Illinois

text: Carbondale is also served by Amtrak Train 390/391, the Saluki, daily in the morning, and Amtrak Train 392/393, the Illini, daily in the afternoon/evening. Both the Saluki and the Illini operate to Chicago, originating and terminating in Carbondale.


title: Carbondale, Illinois

text: Amtrak uses the tracks of the Canadian National Railway, which provides freight service to the city's industrial park. The railroad runs along the original line of the Illinois Central Railroad that began service in 1854 in Carbondale.


title: Carbondale, Illinois

text: The Saluki Express provides bus service around the city. SIUC students, faculty, and staff, as well as the greater Carbondale community, are encouraged to use the service. This system offers eleven routes operating seven days a week while the university is in session, and a "break route" operating during semester breaks.


title: Carbondale, Illinois

text: Local public transit is also provided by Jackson County Mass Transit District six days a week and RidesMTD provides bi-hourly service between Carbondale and Marion six days a week.


title: Emil Michael

text: Emil G. Michael ( ; born September 19, 1972) is an Egyptian-born American businessman. Michael was the Senior Vice President of Business and Chief Business Officer at Uber, and the Chief Operating Officer of Klout.


title: Emil Michael

text: Born in Cairo, Egypt, Michael is a Coptic Christian who moved to the United States with his family in the early 1970s. Michael received his B.A. in Government cum laude from Harvard University, where he wrote for the Harvard Crimson and served as president of the Harvard Republican Club. During his presidency, the club changed its name to the Harvard-Radcliffe Republican Club in an effort to reach out to potential female members. He received his J.D. degree with honors from Stanford Law School.


title: Emil Michael

text: Michael started his career as a strategy consultant at Gemini Consulting's Converging Markets Laboratory in Cambridge, Massachusetts.


title: Emil Michael

text: After law school, Michael served as an Associate in the Communications, Media and Entertainment Investment Banking Group at Goldman Sachs in New York. He also worked on merger and hostile takeover advisory projects and equity and bank debt financing. He left Goldman Sachs in 1999.


title: Emil Michael

text: Michael was an executive at internet-telephony startup Tellme Networks for nine years, from June 1999 until 2008. Tellme was a forerunner of speech recognition technology. The company was sold to Microsoft for approximately $800 million in 2007.


title: Emil Michael

text: Michael was selected as one of 15 White House Fellows during the first year of the Obama administration, where he served as a Special Assistant to U.S. Defense Secretary Robert Gates from 2009 until 2011. Michael has stated that he spent time on assignment in Afghanistan, Pakistan, and other destinations.


title: Emil Michael

text: In July 2012, he became Chief Operating Officer and a member of the Board of Directors of Klout. He held the COO title until September 2013 when he left to join Uber. Klout was sold to Lithium for approximately $200 million in early 2014.


title: Emil Michael

text: Michael joined Uber as Senior Vice President of Business in September 2013. He acted as CEO Travis Kalanick's right-hand-man, helping the company raise nearly $15 billion from key investors worldwide. By February 2018, Uber became the world's most valued private technology company and had raised the most money of any private start-up in history.


title: Emil Michael

text: Michael was a key player in the development of Uber's ride-sharing efforts in China, taking an investment of $2 billion to a value of $7 billion in 2016. He also worked on creating new partnerships with Chinese companies such as Baidu. Michael led the merger of Uber's China operations with that of the local competitor Didi Chuxing in August 2016. In June 2021, Didi raised $4.4 billion in its IPO.


title: Emil Michael

text: In 2017, Michael helped negotiate a deal with Yandex, the largest technology firm and most popular internet search engine in Russia, known as the "Google of Russia," in which Uber owned 36.6 percent of a joint ride-sharing entity in Russia. Uber invested $225 million, and Yandex invested $100 million.


title: Emil Michael

text: In June 2021, Michael was one of several investors that led the funding of Checkstop, AI-based software designed to help moderate content on platforms such as YouTube and Facebook.


title: Emil Michael

text: In August 2019, it was revealed that the Trump administration considered Michael for the job of Secretary of Transportation at the time that Trump was forming his government, in early 2016. The job ended up going to Elaine Chao.


title: Emil Michael

text: Michael, Chairman and CEO of DPCM Capital planned to file for an initial public offering of $250 million for a blank check company. Eric Schmidt is a special advisor to DPCM.


title: Emil Michael

text: While at Uber, Michael became embroiled in a controversy over the company's relationship with journalists. On November 17, 2014, "BuzzFeed" editor-in-chief Ben Smith reported that Uber senior executive Emil Michael "outlined the notion of spending 'a million dollars'" to hire four top opposition researchers and four journalists. He said that team could help Uber fight back against the press by looking into "personal lives, your families". Michael believed his disclosure was "off the record," Michael claimed merely to have asked why journalists can write what he thought were false stories and attack pieces about business people. Michael claims to have suggested that Uber hire a team of opposition researchers and journalists, give them a million-dollar budget, and have the team attack journalists who wrote negative stories about Uber. He specifically targeted Sarah Lacy, a journalist who worked for "Pando Daily" and had criticized the misogynist practices and culture of Uber. Sarah accused Uber of “sexism and misogyny" specifically of Uber's Chief Executive Officer, Travis Kalanick. Travis later made a series of apologetic tweets claiming Emil Michael's comments did not represent the company's views. The controversy made national news and stirred criticism against Uber. Michael later apologized for his words.


title: Emil Michael

text: In 2014, several local Uber employees in Seoul, South Korea, invited Michael with them to visit a "hostess escort-karaoke bar" during a business trip. Four of the other men in the group picked hostesses out of a lineup, and then went to the bar to sing Karaoke. One of the female Uber managers in the group felt uncomfortable during this encounter and reported the event to HR at Uber about one year later. Although the issue had already been resolved, the story came out in March 2017 when Michael contacted Gabi Holzwarth, CEO Kalanick's ex-girlfriend, who had also been in the group at the Karaoke bar, to warn her about an upcoming article in the press. Holzwarth claims that Michael asked her to keep the visit to the hostess bar quiet, among other accusations, in the year after her relationship with Mr. Kalanick ended in 2016. Michael has expressed remorse and apologized for "attending and failing to prevent" the visit to the bar. Three months after the March article, Michael left his position at Uber after four years at the company.


title: Emil Michael

text: In 2014, Michael, and eight others, were appointed to the Pentagon's Defense Business Board. The eight joined 15 members already sitting on the board, which was created in 2002 to provide independent advice on the private sector. Michael was the only one of the new appointees to have experience with startups.


title: Emil Michael

text: Michael was named one of the “Most Creative People in Marketing" and one of the “100 Most Creative People in Business” in 2014 by Fast Company.


title: Emil Michael

text: Michael married his longtime girlfriend, Julie Herrin, in a ceremony in Miami, Florida, in early 2018. The couple met in 2012 in Las Vegas, NV.


title: Luis Alberto (footballer, born 1992)

text: Luis Alberto Romero Alconchel (; born 28 September 1992), known as Luis Alberto, is a Spanish professional footballer who plays as an attacking midfielder or winger for Serie A club Lazio.


title: Luis Alberto (footballer, born 1992)

text: After coming through Sevilla's youth system, he signed with Liverpool in 2013 from Barcelona B, being loaned to Málaga and Deportivo during his contract. In August 2016 he joined Lazio for €4 million, going on to spend several seasons in Serie A with the club.


title: Luis Alberto (footballer, born 1992)

text: A product of Sevilla FC, Luis Alberto was born in San José del Valle, Province of Cádiz, and he spent his first two seasons as a senior with the reserves in Segunda División B, scoring 15 goals in his second. On 16 April 2011 he made his first-team – and La Liga – debut for the Andalusians, replacing another club youth graduate, Rodri, in the second half of a 1–0 away loss against Getafe CF.


title: Luis Alberto (footballer, born 1992)

text: In August 2012, Luis Alberto was loaned to FC Barcelona Atlètic in a one-year deal, with the Catalans having the option to make the move permanent at the end of the season. He made his official debut on 2 September by playing two minutes in a 2–0 home win over CE Sabadell FC, and finished the campaign as second top scorer in the squad, only behind Gerard Deulofeu.


title: Luis Alberto (footballer, born 1992)

text: On 20 June 2013, Sevilla received a £6.8 million offer from Liverpool for Luis Alberto, which was accepted. The signing was completed two days later subject to international clearance, and he made his debut for the English club on 13 July in a 4–0 pre-season friendly win against Preston North End.


title: Luis Alberto (footballer, born 1992)

text: Luis Alberto made his Premier League debut on 1 September 2013, playing the last seven minutes in a 1–0 home victory over Manchester United in place of Philippe Coutinho. On 15 December, shortly after having scored a hat-trick in an under-21 match with the Reds, he provided an assist for Luis Suárez in the 5–0 away demolition of Tottenham Hotspur.


title: Luis Alberto (footballer, born 1992)

text: On 26 June 2014, Luis Alberto was loaned to Málaga CF in a season-long move. In the league opener, on 23 August, he scored the only goal in a home defeat of Athletic Bilbao.


title: Luis Alberto (footballer, born 1992)

text: On 5 July 2015, Luis Alberto agreed a loan move to Deportivo de La Coruña subject to a medical the following day. There, he linked up with manager Víctor Sánchez, who was previously in Sevilla's coaching staff.


title: Luis Alberto (footballer, born 1992)

text: On 31 August 2016, Luis Alberto signed for Italian club S.S. Lazio for a fee of €4 million. He played only nine Serie A matches in his first season, but became an undisputed starter for the Simone Inzaghi-led side from there onwards.


title: Luis Alberto (footballer, born 1992)

text: Luis Alberto scored 12 goals in all competitions in the 2017–18 campaign, and added 18 assists. In October 2020, he tested positive for COVID-19.


title: Luis Alberto (footballer, born 1992)

text: Luis Alberto earned his only cap for the Spain under-21 team on 5 February 2013, coming on for Valencia CF's Paco Alcácer midway through the second half of a 1–1 friendly draw in Belgium. He first appeared with the full side on 11 November 2017, playing the last 16 minutes in a 5–0 friendly win against Costa Rica.


title: Luis Alberto (footballer, born 1992)

text: A talented and versatile playmaker, Luis Alberto usually plays either in a central role as an attacking midfielder or as a left winger, a position which allows him to cut inside and shoot on goal with his stronger right foot. He is also capable of playing in several other attacking positions including second striker, or even in a deeper role as an offensive minded central midfielder, known as the "mezzala" in Italian football jargon. Although he lacks physicality, he is known for his awareness, technical qualities, ball control and dribbling skills, as well as his passing, crossing and vision, which allow him to create chances and provide assists for teammates.


title: Luis Alberto (footballer, born 1992)

text: Moreover, he is an accurate set piece taker who possesses an eye for goal, and has a penchant for shooting from distance. Beyond his offensive qualities, he is also known for his defensive work-rate.


title: Luis Alberto (footballer, born 1992)

text: On 19 January 2021, Luis Alberto underwent a successful emergency surgery in Rome to treat appendicitis.


title: Luis Alberto (footballer, born 1992)

text: He married his longtime girlfriend Patricia Venegas, fathering daughter Martina (born 2016) and son Lucas (2018).


title: Human herpesvirus 6

text: Human herpesvirus 6 (HHV-6) is the common collective name for "human betaherpesvirus 6A" (HHV-6A) and "human betaherpesvirus 6B" (HHV-6B). These closely related viruses are two of the nine known herpesviruses that have humans as their primary host.


title: Human herpesvirus 6

text: HHV-6A and HHV-6B are double-stranded DNA viruses within the "Betaherpesvirinae" subfamily and of the genus "Roseolovirus". HHV-6A and HHV-6B infect almost all of the human populations that have been tested.


title: Human herpesvirus 6

text: HHV-6A has been described as more neurovirulent, and as such is more frequently found in patients with neuroinflammatory diseases such as multiple sclerosis. HHV-6 (and HHV-7) levels in the brain are also elevated in people with Alzheimer's disease.


title: Human herpesvirus 6

text: HHV-6B primary infection is the cause of the common childhood illness exanthema subitum (also known as roseola infantum or sixth disease). It is passed on from child to child. It is uncommon for adults to contract this disease as most people have had it by kindergarten, and once contracted, immunity arises and prevents future reinfection. Additionally, HHV-6B reactivation is common in transplant recipients, which can cause several clinical manifestations such as encephalitis, bone marrow suppression, and pneumonitis.


title: Human herpesvirus 6

text: A variety of tests are used in the detection of HHV-6, some of which do not differentiate the two species.


title: Human herpesvirus 6

text: During 1986, Syed Zaki Salahuddin, Dharam Ablashi, and Robert Gallo cultivated peripheral blood mononuclear cells from patients with AIDS and lymphoproliferative illnesses.


title: Human herpesvirus 6

text: Short-lived, large, refractile cells that frequently contained intranuclear and/or intracytoplasmic inclusion bodies were documented. Electron microscopy revealed a novel virus that they named Human B-Lymphotrophic Virus (HBLV).


title: Human herpesvirus 6

text: Shortly after its discovery, Ablashi et al. described five cell lines that can be infected by the newly discovered HBLV. They published that HSB-2, a particular T-cell line, is highly susceptible to infection. Ablashi's pioneering research concluded by suggesting that the virus name be changed from HBLV to HHV-6, in accord with the published provisional classification of herpes viruses.


title: Human herpesvirus 6

text: Years later, HHV-6 was divided into subtypes. Early research (1992) described two very similar, yet unique variants: HHV-6A and HHV-6B. The distinction was warranted due to unique restriction endonuclease cleavages, monoclonal antibody reactions, and growth patterns.


title: Human herpesvirus 6

text: HHV-6A includes several adult-derived strains and its disease spectrum is not well defined, although it is thought by some to be more neurovirulent. HHV-6B is commonly detected in children with roseola infantum, as it is the etiologic agent for this condition. Within these two viruses is a sequence homology of 95%.


title: Human herpesvirus 6

text: HHV-6A and HHV-6B were recognized by the International Committee on Taxonomy of Viruses (ICTV) as distinct species in 2012. Human Roseoloviruses include HHV-6A, HHV-6B and HHV-7.


title: Human herpesvirus 6

text: "Herpesvirus" was established as a genus in 1971 in the first report of the ICTV. This genus consisted of 23 viruses among 4 groups. In 1976, a second ICTV report was released in which this genus was elevated to the family level — the "herpetoviridae". Because of possible confusion with viruses derived from reptiles, the family name was changed in the third report (1979) to "herpesviridae". In this report, the family "Herpesviridae" was divided into 3 subfamilies ("alphaherpesvirinae", "betaherpesvirinae" and "gammaherpesvirinae") and 5 unnamed genera; 21 viruses were recognized as members of the family.


title: Human herpesvirus 6

text: In 2009, the order "Herpesvirales" was created. This was necessitated by the discovery that the herpes viruses of fish and molluscs are only distantly related to those of birds and mammals. Order "Herpesvirales" contains three families, the "Herpesviridae", which contains the long-recognized herpesviruses of mammals, birds, and reptiles, plus two new families — the family "Alloherpesviridae" which incorporates herpes viruses of bony fish and frogs, and the family "Malacoherpesviridae" which contains viruses of molluscs.


title: Human herpesvirus 6

text: As of 2012, this order currently has 3 families, 4 subfamilies (1 unassigned), 18 genera (4 unassigned) and 97 species.


title: Human herpesvirus 6

text: The diameter of an HHV-6 virion is about 2000 angstroms. The virion's outer portion consists of a lipid bilayer membrane that contains viral glycoproteins and is derived from that of the host. Below this membrane envelope is a tegument which surrounds an icosahedral capsid, composed of 162 capsomeres. The protective capsid of HHV-6 contains double stranded linear DNA.


title: Human herpesvirus 6

text: During maturation of HHV-6 virions, human cell membranes are used to form viral lipid envelopes (as is characteristic of all enveloped viruses). During this process HHV-6 utilizes lipid rafts, which are membranous microdomains enriched by cholesterol, sphingolipids, and glycosylphosphatidylinositol-anchored proteins. Early researchers suspected that HHV-6 virions mature in the nucleus; some even incorrectly published this, as they generalized and applied to HHV-6 what was known about other viruses. However, researched published in 2009 suggests that the HHV-6 virus utilizes trans-Golgi-network-derived vesicles for assembly.


title: Human herpesvirus 6

text: The genetic material of HHV-6 is composed of linear (circular during an active infection), double stranded DNA which contains an origin of replication, two 8–10 kb left and right direct repeat termini, and a unique segment that is 143–145kb.


title: Human herpesvirus 6

text: The origin of replication (often labeled as "oriLyt" in the literature) is where DNA replication begins. The direct repeat termini (DR and DR) possess a repeated TTAGGG sequence, identical to that of human telomeres. Variability in the number of telomeric repeats is observed in the range of 15–180. These termini also contain pac-1 and pac-2 cleavage and packing signals that are conserved among herpesviruses.


title: Human herpesvirus 6

text: The unique segment contains seven major core gene blocks (U27–U37, U38–U40, U41–U46, U48–U53, U56–U57, U66EX2–U77, and U81–U82), which is also characteristic of herpesviruses. These conserved genes code for proteins that are involved in replication, cleavage, and packing of the viral genome into a mature virion. Additionally, they code for a number of immunomodulatory proteins. The unique segment also possesses a block of genes (U2–U19) that are conserved among HHV-6, HHV-7, and Cytomegaloviruses (the betaherpesviruses). A number of the unique segment genes are associated with, for instance, the HCMV US22 family (). The table below outlines some of their known properties.


title: Human herpesvirus 6

text: When an extracellular HHV-6 virion comes across human cells, it encounters the human receptor protein cluster of differentiation 46 (CD46), which plays a role in regulating the complement system. The CD46 protein possesses a single variable region, as a result of alternative splicing. As such, at least fourteen isoforms of CD46 exist, all of which bind HHV-6a.


title: Human herpesvirus 6

text: The extracellular region of CD46 contains four short consensus repeats of about 60 amino acids that fold into a compact beta-barrel domain surrounded by flexible loops. As has been demonstrated for CD46 with other ligands, the CD46 protein structure linearizes upon binding HHV-6. While their precise interaction has not yet been determined, the second and third SCR domains have been demonstrated as required for HHV-6 receptor binding and cellular entry.


title: Human herpesvirus 6

text: Mori et al. first identified the gene product gQ1, a glycoprotein unique to HHV-6, and found that it forms a complex with gH and gL glycoproteins. They believed that this heterotrimer complex served as the viral ligand for CD46. Soon thereafter, another glycoprotein named gQ2 was identified and found to be part of the gH/gL/gQ1 ligand complex, forming a heterotetramer that was positively identified as the viral CD46 ligand. The exact process of entry is not yet well understood.


title: Human herpesvirus 6

text: During the year 2011, researchers at the National Institutes of Health attempted to elucidate the then unknown method whereby HHV-6a gains entry into the nervous system. As such, they autopsied the brains of around 150 subjects. When various anatomical regions were assayed for their viral load, olfactory tissues were found to have the highest HHV-6 content. They concluded that these tissues are the entry point for HHV-6a.


title: Human herpesvirus 6

text: The results above are consistent with those of previous studies that involved HSV-1 (and a number of other viruses), which also disseminates into the CNS through olfactory tissue.


title: Human herpesvirus 6

text: Researchers also hypothesized that olfactory ensheathing cells (OECs), a group of specialized glial cells found in the nasal cavity, may have a role in HHV-6 infectivity. They suspected this association as a result of OECs having properties similar to those of astrocytes, another type of glial cell that was previously identified as being susceptible to HHV-6 infection. Research continued by infecting OECs in vitro with both types of HHV-6. Ultimately, only OECs in which HHV-6a was used tested positive for signs of de novo viral synthesis, as is also characteristic of astrocytes.


title: Human herpesvirus 6

text: Active infections involve the linear dsDNA genome circularizing by end to end covalent linkages. This process was first reported for the herpes simplex virus. Once circularized, HHV-6 begins to express what are known as "immediate early" genes. These gene products are believed to be transcription activators and may be regulated by the expression of viral micro RNAs. Subsequent expression of "early genes" then occurs and activates, for instance, viral DNA polymerases. Early genes are also involved in the rolling circle replication that follows.


title: Human herpesvirus 6

text: HHV-6's replication results in the formation of concatemers, which are long molecules that contain several repeats of a DNA sequence. These long concatemers are then cleaved between the pac-1 and pac-2 regions for packaging of the genome into individual virions.


title: Human herpesvirus 6

text: Not all newly infected cells begin rolling circle replication. Herpesviruses may enter a latent stage, inactively infecting their human host. Since its discovery in 1993, this phenomenon has been found among all of the betaherpesviruses.


title: Human herpesvirus 6

text: Other betaherpesviruses establish latency as a nuclear episome, which is a circular DNA molecule (analogous to plasmids). For HHV-6, latency is believed to occur exclusively through the integration of viral telomeric repeats into human subtelomeric regions. Only one other virus, Marek's disease virus, is known to achieve latency in this fashion. This phenomenon is possible as a result of the telomeric repeats found within the direct repeat termini of HHV-6's genome.


title: Human herpesvirus 6

text: The right direct repeat terminus integrates within 5 to 41 human telomere repeats, and preferentially does so into the proximal end of chromosomes 9, 17, 18, 19, and 22, but has also occasionally been found in chromosomes 10 and 11. Nearly 70 million individuals are suspected to carry chromosomally integrated HHV-6.


title: Human herpesvirus 6

text: A number of genes expressed by HHV-6 are unique to its inactive latency stage. These genes involve maintaining the genome and avoiding destruction of the host cell. For instance, the U94 protein is believed to repress genes that are involved in cellular lysis (apoptosis) and also may aid in telomeric integration. Once stored in human telomeres, the virus is reactivated intermittently.


title: Human herpesvirus 6

text: The specific triggers for reactivation are not well understood. Some researchers have suggested that injury, physical or emotional stress, and hormonal imbalances could be involved.


title: Human herpesvirus 6

text: Researchers during 2011 discovered that reactivation can positively be triggered in vitro by histone deacetylase inhibitors. Once reactivation begins, the rolling circle process is initiated and concatemers are formed as described above.


title: Human herpesvirus 6

text: Human herpesvirus 6 lives primarily on humans and, while variants of the virus can cause mild to fatal illnesses, can live commensally on its host. It has been demonstrated that HHV-6 fosters the progression of HIV-1 upon coinfection in T cells. HHV-6 upregulates the expression of the primary HIV receptor CD4, thus expanding the range of HIV susceptible cells. Several studies also have shown that HHV-6 infection increases production of inflammatory cytokines that enhance in vitro expression of HIV-1, such as TNF-alpha, IL-1 beta, and IL-8. A more recent in vivo study shows HHV-6A coinfection to dramatically accelerate the progression from HIV to AIDS in pigtailed macaques.


title: Human herpesvirus 6

text: Humans acquire the virus at an early age, some as early as less than one month of age. HHV-6 primary infections account for up to 20% of infant emergency room visits for fever in the United States and are associated with several more severe complications, such as encephalitis, lymphadenopathy, myocarditis and myelosuppression. The prevalence of the virus in the body increases with age (rates of infection are highest among infant between 6 and 12 months old) and it is hypothesized that this is due to the loss of maternal antibodies in a child that protect him or her from infections.


title: Human herpesvirus 6

text: There are inconsistencies with the correlations between age and seropositivity: According to some reports there is a decrease of seropositivity with the increase of age, while some indicate no significant decline, and others report an increased rate of seropositivity for individuals age 62 and older. After primary infection, latency is established in salivary glands, hematopoietic stem cells, and other cells, and exists for the lifetime of the host.


title: Human herpesvirus 6

text: The virus is known to be widespread around the world. An HHV-6 infection rate of 64–83% by age 13 months has been reported for countries including the United States, United Kingdom, Japan and Taiwan. Studies have found seroprevalence varying "from approximately 39 to 80% among ethnically diverse adult populations from Tanzania, Malaysia, Thailand, and Brazil." There are no significant differences among ethnic groups living in the same geographical location or between sexes. While HHV-6B is present in almost all of the world's populations, HHV-6A appears to be less frequent in Japan, North America, and Europe.


title: Human herpesvirus 6

text: Transmission is believed to occur most frequently through the shedding of viral particles into saliva. Both HHV-6B and HHV-7 are found in human saliva, the former being at a lower frequency. Studies report varying rates of prevalence of HHV-6 in saliva (between 3–90%), and have also described the salivary glands as an in vivo reservoir for HHV-6. The virus infects the salivary glands, establishes latency, and periodically reactivates to spread infection to other hosts.


title: Human herpesvirus 6

text: Vertical transmission has also been described, and occurs in approximately 1% of births in the United States. This form is easily identifiable as the viral genome is contained within every cell of an infected individual.


title: Human herpesvirus 6

text: The diagnosis of HHV-6 infection is performed by both serologic and direct methods. The most prominent technique is the quantification of viral DNA in blood, other body fluids, and organs by means of real-time PCR.