title: 2007 Australian federal election

text: Election night was covered extensively by three of the Australian free-to-air networks, from the National Tally Room: ABC Television, the Nine Network and the Seven Network. Network Ten and SBS Television included brief updates and news bulletins through the night, but not to the other networks' extent. Sky News offered extensive coverage on Pay TV.


title: 2007 Australian federal election

text: Roy Morgan, Newspoll, ACNeilsen and Galaxy timegraph polling showed Labor leading the Coalition in opinion polling from mid-2006 onward. On several key questions, Labor increased its lead after Rudd assumed the Labor leadership from Kim Beazley, at which point Rudd also assumed the lead as preferred prime minister. While Labor was ahead in opinion polling, Howard had led Beazley on this question by a wide margin.


title: 2007 Australian federal election

text: According to Australian political analyst Adam Carr, WorkChoices was one of five key reasons for "...a change of heart by the decisive sectors of the electorate". The new industrial relations program, Carr said, angered the "Howard battlers" – the traditional Labor voters who had supported Howard for most of the last 11 years – because they saw it as a direct attack on their livelihood.


title: 2007 Australian federal election

text: ACNielsen polling in March 2007 had Rudd's personal approval rating at 67 per cent, which made him the most popular opposition leader in the poll's 35-year history, with Newspoll (News Limited) 2PP polling the highest in its history at 61%. The largest 2PP election result for the ALP in its history was at the 1943 election on an estimate of 58.2 per cent.


title: 2007 Australian federal election

text: A weighted collaboration of all polling since Rudd assumed the ALP leadership shows an average Labor 2PP figure of 57 per cent compared with the Coalition's 43 per cent, and Rudd's consistent outpolling of Howard as preferred prime minister, something not achieved under previous leaders Mark Latham, Kim Beazley or Simon Crean.


title: 2007 Australian federal election

text: By the time the writs were issued, the Coalition was well behind Labor in opinion polling, which election analyst Antony Green believed to show Labor winning government "in a canter". According to Green, this was a nearly exact reversal of the run-up to the 1996 election. The Coalition was running ahead of Labor in two-party opinion polling for much of 1995 and 1996, however the mantle of preferred prime minister regularly switched between Howard and Paul Keating.


title: 2007 Australian federal election

text: Possums Pollytics, an anonymous weblog, stated that due to the uneven nature of the swings, where safe Liberal seats were swinging up to 14.6 per cent with safe Labor seats swinging around only 4.1 points, the Labor party stood to potentially end up with a maximum of 106 of the 151 lower house seats.


title: 2007 Australian federal election

text: Polling consistently showed that the economy and national security were the Coalition's strong areas. In August 2007 an Ipsos poll showed 39 per cent of voters thought Labor was a better economic manager, compared to 36 per cent for the Coalition, with 25 per cent undecided.


title: 2007 Australian federal election

text: The morning of the election announcement, a special Sun-Herald Taverner survey of 979 people across New South Wales and Victoria had been released, indicating a Labor 2PP of 59 per cent, with the 18- to 29-year-old category voting at 72 per cent. The fortnightly Newspoll was released the day after the election was called, showing the 2PP remaining steady at Labor 56–44 Liberal. Howard increased his Preferred PM rating up one per cent to 39 per cent, while Rudd increased his rating up one per cent to 48 per cent. On the day after the election was called, Centrebet had odds of 1.47 on Labor, with 2.70 on the Coalition. Halfway through the campaign, with no overall change in the polls, saw Centrebet odds for Labor shorten to 1.29, with the Liberals on 3.60. Centrebet odds two days out from the election were at 1.22 for Labor, with 4.35 for the Coalition.


title: 2007 Australian federal election

text: Newspoll a week out from the election of 3,600 voters in 18 of the Coalition's most marginal seats revealed an ALP 54–46 Coalition 2PP, a swing to Labor of 6–9 per cent. A uniform swing would see 18–25 seats fall to Labor, The Australian said.


title: 2007 Australian federal election

text: Former Labor number-cruncher Graham Richardson, who news.com.au (News Limited) claims to have correctly picked the winner of every election for the past three decades, tipped Kevin Rudd and Labor to win with a 6–7 per cent two-party-preferred, 20-seat swing.


title: 2007 Australian federal election

text: The election-eve Newspoll and Galaxy poll reported the ALP on a 2PP of 52 per cent, Roy Morgan on 53.5 per cent, with ACNielsen on 57 per cent. Seven News reported that TAB had updated their odds for the election, with Labor having safe odds of $1.20 and the Coalition an outside chance on $4.60.


title: 2007 Australian federal election

text: Sky News-Channel 7-Auspoll exit polls on election day of 2,787 voters in the 31 most marginal seats suggested a 53 per cent two-party preferred figure to Labor, 53 per cent to Labor in Bennelong, and 58 per cent to Labor in Eden-Monaro. Key issue questions swung Labor's way.


title: 2007 Australian federal election

text: At 8.00 pm, the first personality to call the election was former Labor Prime Minister Bob Hawke on Sky News. At 10.29 pm AEST, approximately two hours after the last polls in Western Australia closed, Liberal deputy leader Peter Costello conceded that the Coalition had lost government. At 10.36 pm, John Howard delivered a speech at the Sofitel Wentworth Hotel in Sydney to concede defeat. At 11.05 pm, Kevin Rudd delivered his victory speech.


title: 2007 Australian federal election

text: Labor won 83 of the 150 seats in the incoming House of Representatives. This represented a 23-seat swing to Labor. The Liberals won 55 while the Nationals won 10, with two seats retained by Independents. Labor finished with a 52.70 per cent two-party-preferred vote, a 5.44-point swing from 2004. On preferences, 79.7 per cent of Green votes flowed to Labor, 60.3 per cent of Family First votes flowed to the Coalition, with 62.5 per cent of Democrat votes flowing to Labor. Considering two-party estimates going back to the 1949 election, the swing to Labor in 2007 was the fourth-largest two-party-preferred swing, behind John Curtin and Labor in 1943 on 7.9 per cent, Malcolm Fraser and the Coalition in 1975 on 7.4 per cent, and Gough Whitlam and Labor in 1969 on 7.1 per cent. The swing was the largest since 1983, when full preference counting was introduced to create an exact two-party figure, and the largest swing to occur in the absence of a recession, political or military crisis.


title: 2007 Australian federal election

text: Western Australia went against the national trend, with the Liberals suffering only a 2.14-point swing against them – lower than all except Tasmania and the ACT – but yet gaining one net seat. The weaker Labor performance was attributed to the strong economy and voters' unwillingness to do anything which might risk their present prosperity – a sentiment played to by Liberal campaigning strategies – and also the behaviour of union officials Kevin Reynolds and Joe McDonald who had made headlines during the campaign.


title: 2007 Australian federal election

text: Labor and the Coalition won 18 seats each in the half-Senate election. The Greens won three seats, with Independent Nick Xenophon being elected on primary votes alone. This took the 76-member Senate total to 37 Coalition, 32 Labor, 5 Green, 1 Family First, and 1 Independent. With a majority being 39 senators, when the new Senate met after 1 July 2008, the balance of power was shared between Xenophon, Family First's Steve Fielding and the five Greens. Xenophon, although reported as left-of-centre, indicated plans to work closely with the renegade National, Senator Barnaby Joyce. If sufficient Coalition senators voted for government legislation, support from the crossbench was not required.


title: 2007 Australian federal election

text: Xenophon's election was at the expense of a Liberal candidate, without his presence the Coalition would have held enough Senate seats to block legislation.


title: 2007 Australian federal election

text: Compared to the previous Senate, the Greens gained one (losing Kerry Nettle in NSW but gaining Sarah Hanson-Young in SA and Scott Ludlam in WA), a new Independent was elected (Xenophon), and Labor gained four seats. The Coalition lost two, and the Democrats lost all four of their seats.


title: 2007 Australian federal election

text: The informal rate of 2.55 per cent ties with the 1993 election as the lowest informal rate in the Senate since federation. The introduction of the group voting ticket at the 1984 election saw the number of informal votes drop dramatically.


title: 2007 Australian federal election

text: Prime Minister John Howard lost his own seat of Bennelong, in Northern Sydney, to Labor candidate and former journalist Maxine McKew, becoming the second sitting prime minister, and the third party leader, since Federation to be defeated in his own electorate. Prime Minister Stanley Bruce and National Party leader Charles Blunt lost their seats in 1929 and 1990 respectively. Howard had held the seat since 1974, and it had been in Liberal hands ever since its creation in 1949.


title: 2007 Australian federal election

text: However, successive redistributions, along with demographic change, had made the once safe Liberal seat much friendlier to Labor; much of the area was represented by Labor at the state level. Howard's two-party majority was four percent, putting it right on the edge of seats that Labor would likely take in the event it won.


title: 2007 Australian federal election

text: Late on election night, when conceding Labor had won government, Howard also acknowledged the likelihood he had lost Bennelong to McKew, though he and McKew agreed the margin was "very tight". He had been ahead by thin margins for most of the night, never leading by more than 0.2 percentage points. Howard had been 206 votes ahead of McKew on the first count, and finished 2.8 percentage points behind McKew on the estimated two-party vote. McKew declined to claim victory at first, saying that the seat was on "a knife edge," while the Australian Broadcasting Corporation listed Bennelong as a Labor gain on election night, and ABC election analyst Antony Green said there was "no doubt" McKew had won.


title: 2007 Australian federal election

text: On 29 November, Rudd named McKew as a parliamentary secretary (assistant minister) to be appointed on 3 December, and on 1 December, McKew claimed victory. Although counting was incomplete at the time, with several postal and absentee ballots outstanding, it was expected that Howard would not win enough of the votes to retain his seat. McKew finished with a primary vote of 45.33 per cent, and a two-party-preferred vote of 51.40 per cent, a 5.53-point swing from 2004. Howard lost on the 14th count due to a large flow of Green preferences to McKew. This swing was within the redistributed boundaries after the 2004 election.


title: 2007 Australian federal election

text: The following table indicates seats that changed hands from one party to another at this election. It compares the election results with the previous margins, taking into account the redistribution in New South Wales and Queensland. As a result, it includes the newly created electorate of Flynn, and the existing Parramatta, which was retained by Labor despite becoming a notional Liberal seat due to boundary changes. The table does not include Gwydir, which was abolished in the redistribution; Macquarie, which was reclassified from safe Liberal to marginal Labor and was subsequently won by Labor; or Calare, the seat of Independent MP Peter Andren, which was reclassified as a National seat by the redistribution and was won by the National Party.


title: 2007 Australian federal election

text: The Labor caucus met on Thursday 29 November 2007 to confirm the First Rudd Ministry, which was sworn in on 3 December. In a departure from Labor tradition, the ministry was selected by Kevin Rudd as the prime minister, rather than by Caucus.


title: 2007 Australian federal election

text: Given John Howard's personal defeat, the Liberal Party began the process of choosing a new leader. The morning after the election, Peter Costello, the Deputy Leader of the Liberal Party, and long regarded as Howard's natural successor, stated that he would not run for Liberal leadership. The day before the ballot, former Health Minister Tony Abbott withdrew from the leadership after initially indicating he would stand. The leadership ballot was held on Thursday 29 November. The previous Defence Minister Brendan Nelson and former Environmental Minister Malcolm Turnbull both stood for the leadership. Former Education Minister Julie Bishop contested the deputy leadership position, as did Andrew Robb and Christopher Pyne.


title: 2007 Australian federal election

text: Brendan Nelson was elected leader by 45 votes to 42, and Julie Bishop was elected deputy leader. A Newspoll survey taken after the Liberal leadership change revealed a preferred-prime-minister rating of Rudd 61 per cent to Nelson 14 per cent, with Turnbull twice as popular as Nelson. Newspoll's subsequent polling saw new Newspoll records set, at 70 per cent for the best rating for preferred prime minister, to 9 per cent for the worst rating for preferred prime minister, with the next poll results revealing another record of 73 to 7 per cent. A new two party preferred record was also set, at 63 to 37 per cent Labor's way.


title: 2007 Australian federal election

text: Post-election, ALP secretary Tim Gartrell commented on pre-election campaign billboard ads featuring a picture of John Howard stating "Working families in Australia have never been better off", which looked like Liberal Party advertisements, were actually paid for by the Labor Party. Liberal leader Brendan Nelson declared that the Liberal Party had listened and learned from the Australian public and declared WorkChoices "dead".


title: 2007 Australian federal election

text: In 2008, former ministers Peter McGauran, Alexander Downer, and Mark Vaile resigned from parliament, sparking Gippsland, Mayo, and Lyne by-elections. The Lyne by-election resulted in independent Rob Oakeshott being elected, reducing the total number of Coalition seats to 64. Bradfield and Higgins by-elections were held in December 2009.


title: 2007 Australian federal election

text: In September 2008, Malcolm Turnbull replaced Brendan Nelson in a leadership spill, and Barnaby Joyce replaced CLP Senator and Nationals deputy leader Nigel Scullion as leader of the Nationals in the Senate, and moved the party to the crossbenches. Joyce stated that his party would no longer necessarily vote with their Liberal counterparts in the upper house.


title: Balmer series

text: The Balmer series, or Balmer lines in atomic physics, is one of a set of six named series describing the spectral line emissions of the hydrogen atom. The Balmer series is calculated using the Balmer formula, an empirical equation discovered by Johann Balmer in 1885.


title: Balmer series

text: The visible spectrum of light from hydrogen displays four wavelengths, 410 nm, 434 nm, 486 nm, and 656 nm, that correspond to emissions of photons by electrons in excited states transitioning to the quantum level described by the principal quantum number "n" equals 2. There are several prominent ultraviolet Balmer lines with wavelengths shorter than 400 nm. The number of these lines is an infinite continuum as it approaches a limit of 364.5 nm in the ultraviolet.


title: Balmer series

text: After Balmer's discovery, five other hydrogen spectral series were discovered, corresponding to electrons transitioning to values of "n" other than two .


title: Balmer series

text: The Balmer series is characterized by the electron transitioning from "n" ≥ 3 to "n" = 2, where "n" refers to the radial quantum number or principal quantum number of the electron. The transitions are named sequentially by Greek letter: "n" = 3 to "n" = 2 is called H-α, 4 to 2 is H-β, 5 to 2 is H-γ, and 6 to 2 is H-δ. As the first spectral lines associated with this series are located in the visible part of the electromagnetic spectrum, these lines are historically referred to as "H-alpha", "H-beta", "H-gamma", and so on, where H is the element hydrogen.


title: Balmer series

text: Although physicists were aware of atomic emissions before 1885, they lacked a tool to accurately predict where the spectral lines should appear. The Balmer equation predicts the four visible spectral lines of hydrogen with high accuracy. Balmer's equation inspired the Rydberg equation as a generalization of it, and this in turn led physicists to find the Lyman, Paschen, and Brackett series, which predicted other spectral lines of hydrogen found outside the visible spectrum.


title: Balmer series

text: The red H-alpha spectral line of the Balmer series of atomic hydrogen, which is the transition from the shell "n" = 3 to the shell "n" = 2, is one of the conspicuous colours of the universe. It contributes a bright red line to the spectra of emission or ionisation nebula, like the Orion Nebula, which are often H II regions found in star forming regions. In true-colour pictures, these nebula have a reddish-pink colour from the combination of visible Balmer lines that hydrogen emits.


title: Balmer series

text: Later, it was discovered that when the Balmer series lines of the hydrogen spectrum were examined at very high resolution, they were closely spaced doublets. This splitting is called fine structure. It was also found that excited electrons from shells with "n" greater than 6 could jump to the "n" = 2 shell, emitting shades of ultraviolet when doing so.


title: Balmer series

text: Balmer noticed that a single wavelength had a relation to every line in the hydrogen spectrum that was in the visible light region. That wavelength was . When any integer higher than 2 was squared and then divided by itself squared minus 4, then that number multiplied by (see equation below) gave the wavelength of another line in the hydrogen spectrum. By this formula, he was able to show that some measurements of lines made in his time by spectroscopy were slightly inaccurate and his formula predicted lines that were later found although had not yet been observed. His number also proved to be the limit of the series.


title: Balmer series

text: The Balmer equation could be used to find the wavelength of the absorption/emission lines and was originally presented as follows (save for a notation change to give Balmer's constant as "B"):


title: Balmer series

text: In 1888 the physicist Johannes Rydberg generalized the Balmer equation for all transitions of hydrogen. The equation commonly used to calculate the Balmer series is a specific example of the Rydberg formula and follows as a simple reciprocal mathematical rearrangement of the formula above (conventionally using a notation of m for n as the single integral constant needed):


title: Balmer series

text: where "λ" is the wavelength of the absorbed/emitted light and "R" is the Rydberg constant for hydrogen. The Rydberg constant is seen to be equal to in Balmer's formula, and this value, for an infinitely heavy nucleus, is  = .


title: Balmer series

text: The Balmer series is particularly useful in astronomy because the Balmer lines appear in numerous stellar objects due to the abundance of hydrogen in the universe, and therefore are commonly seen and relatively strong compared to lines from other elements.


title: Balmer series

text: The spectral classification of stars, which is primarily a determination of surface temperature, is based on the relative strength of spectral lines, and the Balmer series in particular is very important. Other characteristics of a star that can be determined by close analysis of its spectrum include surface gravity (related to physical size) and composition.


title: Balmer series

text: Because the Balmer lines are commonly seen in the spectra of various objects, they are often used to determine radial velocities due to doppler shifting of the Balmer lines. This has important uses all over astronomy, from detecting binary stars, exoplanets, compact objects such as neutron stars and black holes (by the motion of hydrogen in accretion disks around them), identifying groups of objects with similar motions and presumably origins (moving groups, star clusters, galaxy clusters, and debris from collisions), determining distances (actually redshifts) of galaxies or quasars, and identifying unfamiliar objects by analysis of their spectrum.


title: Balmer series

text: Balmer lines can appear as absorption or emission lines in a spectrum, depending on the nature of the object observed. In stars, the Balmer lines are usually seen in absorption, and they are "strongest" in stars with a surface temperature of about 10,000 kelvins (spectral type A). In the spectra of most spiral and irregular galaxies, active galactic nuclei, H II regions and planetary nebulae, the Balmer lines are emission lines.


title: Balmer series

text: In stellar spectra, the H-epsilon line (transition 7→2, 397.007 nm) is often mixed in with another absorption line caused by ionized calcium known as "H" (the original designation given by Joseph von Fraunhofer). H-epsilon is separated by 0.16 nm from Ca II H at 396.847 nm, and cannot be resolved in low-resolution spectra. The H-zeta line (transition 8→2) is similarly mixed in with a neutral helium line seen in hot stars.


title: Nutty Professor II: The Klumps

text: Nutty Professor II: The Klumps is a 2000 American science fiction dark comedy film directed by Peter Segal. It is a sequel to the 1996 film "The Nutty Professor".


title: Nutty Professor II: The Klumps

text: In contrast to the previous film, subplots which are centered on the parents of protagonist Sherman Klump occupy a substantial part of the film. Members of the Klump family, including Sherman's parents, also provide an increased level of comic relief.


title: Nutty Professor II: The Klumps

text: Professor Sherman Klump has created a new de-aging formula. He is also in love with DNA researcher, Denise Gaines, developer of a method to isolate genetic material. Despite his good fortune, Sherman's major problem is his id alter ego, Buddy Love. He is still ingrained inside him and has begun to periodically take control of his body. Buddy's antics culminate in the corruption of Sherman's attempted proposal to Denise into a mortifying display of perversion.


title: Nutty Professor II: The Klumps

text: Determined to be rid of Buddy permanently, and despite his assistant, Jason, warning him of potential consequences, Sherman uses Denise's methodology to isolate and remove the DNA where Buddy has manifested. However, the Buddy genetic material grows into a sentient being when a hair from Jason's Basset Hound, Buster, accidentally lands in it. Sherman apologizes to Denise and they become engaged. Later, Dean Richmond informs them that Phleer Pharmaceuticals has offered Wellman College $150 million for the youth formula.


title: Nutty Professor II: The Klumps

text: Sherman and Denise then encounter the newly reformed Buddy at a movie theater. Buddy pickpockets Sherman and learns of the $150 million offer. He subsequently visits the pharmaceutical company, making a rival bid of $149 million with Leanne Guilford, President of Acquisitions, for the youth formula. Sherman learns that the extraction has altered his body chemistry and that he is losing his intelligence. Realizing he needs to keep the youth formula out of Buddy's hands, Sherman stashes it at his parents'.


title: Nutty Professor II: The Klumps

text: Sherman's sexually frustrated father Cletus accidentally drinks some of the youth formula. He goes out for a night on the town and attempts to seduce his wife and Sherman's mother, Anna, but she is horrified. Buddy witnesses Cletus changing and realizes that the youth formula is being stored in the Klump household. Meanwhile, Sherman's condition causes him to act like a fool in front of Denise's parents, concerning her.


title: Nutty Professor II: The Klumps

text: Buddy steals some of the youth formulae from the Klump household, filling the vial the rest of the way with fertilizer. This sabotage causes chaos at a demonstration the next day as Petey, the male hamster Sherman uses to demonstrate the formula, mutates into a giant monster who violates Richmond as he is trying to escape under a fur coat, as Petey confuses him for Molly, the female hamster that escaped during the event. The humiliated and enraged Richmond fires Sherman, who soon learns from Jason that his brain's deterioration has worsened, so he decides to break up with Denise. Cletus reconciles with Anna, and consoles a depressed Sherman.


title: Nutty Professor II: The Klumps

text: Sherman quickly works on a newer, much more potent formula while his mental faculties allow him. Richmond confronts him about Buddy's actions, believing that they are working together. Sherman leaves with Richmond and a tennis ball covered in the youth formula and heads to a presentation at Phleer Pharmaceuticals that Buddy is giving about the youth formula. Meanwhile, a worried Denise discovers what has happened and that Sherman's brain damage is progressing. With Cletus' help, Denise goes after him. Sherman takes advantage of the canine DNA crossed with Buddy's and uses the tennis ball to distract him. Buddy catches the ball in his mouth, and the youth formula transforms him back into a glowing mass of sentient genetic material.


title: Nutty Professor II: The Klumps

text: Sherman chases the genetic material, intent on drinking it to correct his condition. However, it evaporates on the edge of a fountain before he can. Cletus and Denise arrive too late to save him, and Denise breaks into tears, which hit the genetic material and fall into the fountain. As they go to leave, Sherman looks into the fountain, remarking that it is "pretty". Seeing the water is glowing, Denise realizes the genetic material has reconstituted thanks to her tears and that if Sherman drinks the fountain water, he will be restored to normal. When he drinks it, he is able to restore his intelligence.


title: Nutty Professor II: The Klumps

text: Additionally, Kathleen Freeman makes an uncredited appearance as Denise's neighbor who witnesses Sherman proposing to her. Freeman previously portrayed Millie Lemmon in the original 1963 film.


title: Nutty Professor II: The Klumps

text: "Nutty Professor II: The Klumps" grossed over $42.5 million in its opening weekend and went on to a total gross of over $123.3 million in the United States beating out "Thomas and the Magic Railroad". It earned an additional $43 million in other territories, for a worldwide total of $166.3 million worldwide.


title: Nutty Professor II: The Klumps

text: Unlike the first film, "Nutty Professor II: The Klumps" received unfavorable reviews from critics. Adjectives such as "obnoxious", "lowbrow", "bloated", and "unfunny" cropped up frequently in reviews. On Rotten Tomatoes the film has an approval rating of 26% based on reviews from 88 critics. The site's consensus states that "While Eddie Murphy is still hilarious as the entire Klump family, the movie falls apart because of uneven pacing, a poor script, and skits that rely on being gross rather than funny." On Metacritic the film has a score of 38 out of 100, a score that indicates generally unfavorable reviews, based on reviews from 34 critics. Audiences surveyed by CinemaScore gave the film a grade A− on scale of A to F.


title: Nutty Professor II: The Klumps

text: Salon.com's reviewer gave the movie one of its few positive notices, and offered the praise "cheerfully vulgar".


title: Nutty Professor II: The Klumps

text: "The New Yorker's" Anthony Lane was particularly severe; in addition to hating the film, he dismissed Murphy's playing of multiple characters as "minstrelling", and charged the actor with "at once feeding us what we like and despising us for swallowing it." Most critics gave a generally negative assessment of the movie with at least a nod towards Murphy's versatility and comic talent.


title: Nutty Professor II: The Klumps

text: Roger Ebert gave the film three stars, noting that while it was "raucous" and "scatological," the film overall proved to be "very funny" and "never less than amazing."


title: Nutty Professor II: The Klumps

text: Variety's Joe Leydon wrote: "Be prepared to laugh less at a lot more of the same thing in this overbearing but underwhelming sequel."


title: David Banner

text: Lavell William Crump (born April 11, 1974), better known by his stage name David Banner, is an American rapper, record producer, and actor.


title: David Banner

text: Born in Brookhaven, Mississippi, Banner's family moved to Jackson, Mississippi, where he was raised. Banner graduated from Southern University with a bachelor's degree, then attended University of Maryland Eastern Shore to pursue a master's. He started his music career as a member of the rap duo, Crooked Lettaz, before going solo in 2000 with the release titled "Them Firewater Boyz, Vol. 1". In 2003, Banner signed to Universal Records, where he released four albums: "" (2003), "" (2003), "Certified" (2005), and "The Greatest Story Ever Told" (2008).


title: David Banner

text: Banner is also a noted producer, having produced music for himself, Trick Daddy, T.I., Lil Boosie and Lil Wayne among others.


title: David Banner

text: Lavell William Crump was born in Brookhaven and raised in Jackson, Mississippi, the elder son of Zeno Crump Jr., Jackson district fire chief, and Carolyn Crump. He graduated from Provine High School in Jackson in 1992 and then attended Southern University in Baton Rouge, Louisiana, his mother's alma mater. At Southern University, Crump served as president of the Student Government Association and received a bachelor's degree in business. He later attended the University of Maryland Eastern Shore to pursue a master's degree in education but later left the program to pursue his music career full-time.


title: David Banner

text: Crump's stage name "David Banner" is taken from the lead character of the television series, "The Incredible Hulk". With several of his friends, Banner sent some demo tapes to Jackson, Mississippi radio station, WJMI. Celebrity Manager Glenn Sweety G Toby discovered the group and signed them to Neil Levine at Penalty Records. In 1999, Banner and rapper Kamikaze as the duo, Crooked Lettaz, released "Grey Skies" (Penalty Recordings). In 2000, Banner released his solo debut album, "Them Firewater Boyz, Vol. 1". Released on the independent label, Big Face Records, the album sold around 7,000 copies.


title: David Banner

text: After assessing various offers, Banner and manager, Scott Johnson, decided to sign with Universal Records subsidiary, SRC Records, which was founded by Steve Rifkind who had previous success as CEO of the heavyweight hip-hop label, Loud Records. In 2003, Banner produced T.I.'s single, "Rubber Band Man", which reached No. 30 on the Hot 100, No. 15 on the R&B chart, and No. 11 on the Rap chart. In 2003, Banner released his first major label album, "". "Mississippi" included the hit single, "Like a Pimp", featuring Lil Flip. "Like a Pimp" peaked at No. 48 on the "Billboard" Hot 100 chart, No. 15 on the Hot R&B/Hip-Hop Songs chart, and No. 10 on the Hot Rap Tracks chart. He released the follow-up album the same year titled "" which yielded the hit, "Crank It Up", featuring Static Major.


title: David Banner

text: In 2005, Banner released his third major label album, "Certified". The album's first single was "Ain't Got Nothing" which featured Magic & Lil Boosie, followed by the second single, "Play", which reached No. 7 on the Hot 100 chart, No. 5 on the R&B chart, and No. 3 on the Rap chart. The third single, "Touching", featured Jazze Pha and reached No. 54 on the R&B chart. In 2006, Banner appeared on "Seein' Thangs", a song about Hurricane Katrina featured on DJ Shadow's album "The Outsider". A remix featuring Bay Area hyphy rappers Nump and Gold also was made. Outside projects for Banner have included writing the theme song to the video game, "Saints Row", as well as contributing to the music for a commercial promoting the video game, "". Banner played the part of Tehronne in "Black Snake Moan" (2006).


title: David Banner

text: Banner appeared on the Adult Swim pilot "That Crook'd 'Sipp", which premiered on May 13, 2007. His single "Play" was used as the background music in the pilot's first television promo. That same year, he played the character of Mo, in the film "This Christmas". On July 15, 2008, Banner released his fourth major label album, "The Greatest Story Ever Told". The album's first single titled "9mm" featured Akon, Lil Wayne, and Snoop Dogg. Banner then produced his next two singles: "Get Like Me" featuring Chris Brown and Yung Joc, "Get Like Me" reached No. 16 on the Hot 100, No. 7 on the R&B chart, and No. 2 on the Rap chart. and "Shawty Say", featuring Lil Wayne. In 2008, Banner was featured on the track, "Superfriend", from the 2008 album, "The Sound", by gospel R&B duo, Mary Mary.


title: David Banner

text: In 2010, he played Bosch in the film The Experiment and as Jay, a gang leader from the hood in "". He has also worked with international artists such as Seeda, a Japanese Rap Artist where he was featured in the song, Life Song in 2010 on Seeda's Breathe Album. Banner released his debut mixtape titled "Sex, Drugs and Video Games" on May 22, 2012, as a free download. It is also available on his website, davidbanner.com, where fans are encouraged to make a donation of at least $1 for the sixteen song mixtape. The first single off the mixtape is titled "Amazing" featuring Chris Brown. It was announced that Universal Republic Records was going defunct, all of the artists on the roster moved from the label including (David Banner) was being moved to Republic Records making the label itself revived.


title: David Banner

text: In 2013, David Banner appeared in the music video for the song "Confessions" by Lecrae. Banner played Earl Gaines, Cecil Gaines' father, in the 2013 film "The Butler". Banner plays Jay, a criminal who is interrogated, in the 2014 film "Ride Along." David Banner was featured on a remix of Mexican American rapper Kap G's single "La Policia", which stirred hype throughout the media and the internet.


title: David Banner

text: In November 2006, Banner was awarded a Visionary Award by the National Black Caucus of State Legislators in Jackson, Mississippi in recognition of his humanitarian work in response to Hurricane Katrina.


title: David Banner

text: On September 25, 2007, Banner testified before Congress at a hearing about racism and misogyny in hip hop music titled "From Imus to Industry: The Business of Stereotypes and Degrading Images". He defended his use of offensive language and argued: "Change the situation in my neighborhood and maybe I'll get better." In his opening statement, Banner stated: "I can admit there are some problems in hip hop but it is only a reflection of what's taking place in our society. Hip hop is sick because America is sick."


title: Takuma Sato

text: , nicknamed "Taku", is a Japanese professional racing driver. Sato is a two time winner of the Indianapolis 500, having won the event in 2017 and 2020. He was the first Asian driver to win the Indianapolis 500, and the twentieth driver to win the race more than once. Before winning the Indianapolis 500, Sato became the first Japanese-born driver to win an IndyCar Series race when he won the 2013 Grand Prix of Long Beach. He currently drives for Dale Coyne Racing with Rick Ware Racing.


title: Takuma Sato

text: Sato has raced full-time in the IndyCar Series since 2010 for KV Racing Technology, Rahal Letterman Lanigan Racing, A. J. Foyt Enterprises, and Andretti Autosport, all with Honda engines.


title: Takuma Sato

text: He competed in Formula One from 2002 to 2008 for the Honda-powered Jordan, BAR and Super Aguri teams, scoring 44 points overall, and a single podium which was at the 2004 United States Grand Prix. His 8th-place finish in the 2004 Formula One World Drivers' Championship is the best-ever result for a Japanese driver in the series.


title: Takuma Sato

text: Sato has become known among fans and media for his motto ""no attack, no chance"" with regards to his racing style.


title: Takuma Sato

text: Born in Tokyo, Sato began karting in Japan at the age of 19. After winning the national karting title in 1997, he moved to Europe with backing from Honda. He briefly raced in Vauxhall Junior and Formula Opel, before debuting in Class B of the British Formula 3 Championship mid-way through 1999. He moved to the top class of the championship with Carlin Motorsport in 2000, taking four wins and third place in the championship. In 2001, he won 12 out of 26 races to take a dominant championship win, the first for a Japanese driver in the series. In 2001 he also won the prestigious Macau Grand Prix and Masters of Formula 3 non-championship F3 races.


title: Takuma Sato

text: In Sato graduated to Formula One with the Honda-powered Jordan team, and was paired with Giancarlo Fisichella. His low point was a tremendous crash in Austria, caused when Nick Heidfeld lost control of his Sauber under braking and hit the side of Sato's car, punching a hole in the side of the cockpit. Throughout he showed flashes of speed but also wild driving, nevertheless the team's faith in Sato was repaid by a fine drive to fifth at his home Grand Prix in Suzuka.


title: Takuma Sato

text: With Honda's focus shifting solely to British American Racing for , Sato joined the Brackley-based outfit as a test driver. For the final round in Japan, Sato replaced Jacques Villeneuve and scored the second points finish of his career with sixth place, after a battle with Michael Schumacher. He was signed to race full-time in 2004. During the 2004 season, Sato qualified four times in the top-three, including a front row start and an overall lap record at the European Grand Prix. Sato's aggressive driving style paid dividends at the , where, after the team did not pit under safety car conditions, Sato fought back with some daring overtaking moves to score his first podium finish and the first for a Japanese driver since Aguri Suzuki at the 1990 Japanese Grand Prix. Reliability issues caused him to retire six times, but he scored points in nine of the 11 races he completed to finish eighth in the championship with 34 points, the best-ever result for a Japanese driver in Formula One. His efforts helped BAR-Honda to finish second in the Constructors' Championship.


title: Takuma Sato

text: Sato was retained by BAR-Honda for the 2005 season, but the 2005 car was not as close to the front of the pack as the previous year's design. Sato missed the with illness, and both drivers were disqualified from the and the entire team banned from the two subsequent races for using cars that were underweight when all fuel was removed. The Court did not find that this was deliberate. Sato's season never recovered from that point, and he ended the season with eighth-place at the Hungarian Grand Prix as his only points finish, despite qualifying seven times in the top ten. Sato was not re-signed for 2006, despite Honda taking full control of the team.


title: Takuma Sato

text: Sato joined the new Super Aguri F1 team for , run by Japanese former driver Aguri Suzuki. The new outfit was in effect a Honda B-team but ran the first half of the season with a modified version of a 2002 Arrows A23 chassis. Nevertheless, Sato's reputation improved thanks to his professional attitude and competitive spirit. The team introduced a new car, the SA06 at the and by the end of the season, Sato was outpacing the Midland cars. At the season finale in Brazil Sato finished tenth just two places short of a points finish and comfortably ahead of both Toro Rossos and the Spyker MF1s.


title: Takuma Sato

text: For 2007, Super Aguri ran a reworked version of the previous year's Honda RA106 chassis. Their performance improved drastically as Sato made it through to Q3 at the . He then scored the first point for the team at the . At the , Sato finished sixth after having a race that had seen him move from the middle of the grid to a high of fifth, passing Ferrari's Kimi Räikkönen before a pit-stop error dropped him back to eleventh. He moved up five places in the last 15 laps, passing Toyota's Ralf Schumacher and then on lap 67 the McLaren-Mercedes of Fernando Alonso; the latter pass was met with cheers around the track and received him the "Overtake of the Year" award from "F1 Racing" magazine.


title: Takuma Sato

text: Financial problems began to affect the team in the off-season and the squad only just made it to the opening round of the season in Australia. The team used a modified Honda RA107 chassis, which was launched just before the first Friday Practice session that weekend. A transmission issue in Australia ended an opportunity to score points in a race of attrition, and 13th in Spain turned out to be Sato's best result of the season. Due to the financial struggles, Super Aguri withdrew from Formula One after the Spanish Grand Prix, leaving Sato without a drive after four races in 2008.


title: Takuma Sato

text: In late 2008, Sato took part in tests at Jerez with Scuderia Toro Rosso, to become a candidate to fill the seat vacated by Sebastian Vettel. He was competing against former Toro Rosso driver Sébastien Bourdais and Red Bull Racing test and reserve driver Sébastien Buemi for one of the two race seats. He first drove on 18 September, more than four months since Super Aguri's withdrawal, and tested for the team again for two days in November, setting the fastest time on the 17th, 3 tenths ahead of Buemi, and proceeded by setting the second-fastest time on the 18th. The race seat was eventually given to Bourdais, and in March 2009 it was announced that Sato would not be the reserve driver for the Red Bull team.


title: Takuma Sato

text: Sato visited the Indianapolis 500 in May 2009. He signed with KV Racing Technology to drive in the 2010 IndyCar Series season finishing in 21st place. He signed for the same team for 2011 and improved his form, scoring three top-five finishes and two pole positions during the season to finish 13th.


title: Takuma Sato

text: At the 2012 Indianapolis 500, driving for Rahal Letterman Lanigan Racing, Sato chased Dario Franchitti to the finish making a move for the lead and the race win at the first turn of the last lap. While not successful, Sato was respected by Indianapolis 500 fans for "going for it" on the last lap.


title: Takuma Sato

text: For 2013, Sato joined A. J. Foyt's team, driving the No. 14 car vacated by Mike Conway. In the third race of the season at Long Beach, Sato scored his first IndyCar win, in his 52nd start in the series, making him the first Japanese driver to win an IndyCar race. He then scored six top-five finishes, including two podiums and two pole positions, until he left the team at the end of 2016.


title: Takuma Sato

text: Sato joined Andretti Autosport for the 2017 season. He went on to become the first Japanese driver to win the Indianapolis 500. After the 500 win, he went on to win a pole at the Dual in Detroit on Belle Isle. He also ended up winning another pole at Pocono Raceway in August.


title: Takuma Sato

text: On 26 August 2017, it was reported that in 2018, Sato would rejoin RLL to drive the 30 car with Graham Rahal as his teammate as Andretti Autosport considered a move to Chevrolet in 2018. That move by Andretti subsequently did not happen. After numerous weeks of bad luck including crashing early in the Indianapolis 500 and wrecking early at Pocono and a failed pit strategy at Gateway, Sato played the strategy right and held off Ryan Hunter-Reay in the IndyCar return to Portland, winning his third career race and his first on a permanent road course, doing so from 20th starting position. Sato started his 2019 season with a win in the third race at Barber Motorsports Park; he started the race from pole position and ran away to the finish. Sato won later in the season at World Wide Technology Raceway at Gateway.


title: Takuma Sato

text: On 23 August 2020, after qualifying on the outside of the front row for the 104th running of the Indianapolis 500, Sato won the race for a second time.


title: Takuma Sato

text: On 5 October 2021, it was announced that Sato would not return to the team for the 2022 IndyCar season. His spot in the team was taken over by Danish driver, Christian Lundgaard.


title: Takuma Sato

text: On 9 December 2021, it was announced that Sato had signed with Dale Coyne Racing with Rick Ware Racing for the 2022 season, replacing Romain Grosjean, who had signed with Andretti Autosport. He finished 25th at the Indianapolis 500.


title: Takuma Sato

text: On 14 June 2012, Team Mugen announced that Sato would race with the team in the last three rounds of the 2012 Formula Nippon season. He also raced with Team Mugen in the opening round of the renamed 2013 Super Formula season, and later in the year returned to the team to compete in the last three races of the season; he scored his first points with an eighth-place finish in the season finale.


title: Takuma Sato

text: In November 2013, Sato became a test and development driver for the FIA Formula E Championship. In September 2014, Sato joined his former Formula One team Amlin Aguri to race in the first-ever Formula E race, the 2014 Beijing ePrix, replacing the team's regular driver Antonio Félix da Costa as he could not participate due to other commitments. Sato scored two points after he set the fastest lap of the race with a time of 1:45.101, but had to retire from the race with mechanical issues. As it was Sato's only Formula E race, he became the only driver in the series' history with a 100% fastest lap record.


title: Takuma Sato

text: Sato is married to Chiharu Sato, with whom he has two children. He currently lives in Carmel, Indiana with his manager, Steve Fusek. Sato was a national cycling champion in high school, and still uses cycling as part of his physical training for his racing career.


title: Takuma Sato

text: "The 2011 Las Vegas Indy 300 was abandoned after Dan Wheldon died from injuries sustained in a 15-car crash on lap 11."


title: VVT-i

text: VVT-i, or Variable Valve Timing with intelligence, is an automobile variable valve timing technology developed by Toyota. It was first introduced in 1995 with the "2JZ-GE" engine found in the JZS155 Toyota Crown and Crown Majesta.


title: VVT-i

text: The VVT-i system replaces the Toyota VVT system first introduced in 1991 with the five-valve per cylinder "4A-GE" engine found in the AE101 Corolla Levin and Sprinter Trueno. The VVT system is a 2-stage hydraulically controlled cam phasing system.


title: VVT-i

text: VVT-i varies the timing of the intake valves by adjusting the relationship between the camshaft drive (belt or chain) and intake camshaft. Engine oil pressure is applied to an actuator to adjust the camshaft position. Adjustments in the overlap time between the exhaust valve closing and intake valve opening result in improved engine efficiency. Variants of the system, including VVTL-i, Dual VVT-i, VVT-iE, VVT-iW and Valvematic, have followed.


title: VVT-i

text: VVTL-i (Variable Valve Timing and Lift intelligent system) (also sometimes denoted as VVT-iL or Variable Valve Timing and Intelligence with Lift) is an enhanced version of VVT-i that can alter valve "lift" (and "duration") as well as valve timing. In the case of the 16-valve "2ZZ-GE", the engine head resembles a typical DOHC design, featuring separate cams for intake and exhaust and featuring two intake and two exhaust valves (four total) per cylinder. Unlike a conventional design, each camshaft has two lobes per cylinder, one optimized for lower rpm operation and one optimized for high rpm operation, with higher lift and longer duration. Each valve pair is controlled by one rocker arm, which is operated by the camshaft. Each rocker arm has a slipper follower mounted to the rocker arm with a spring, allowing the slipper-follower to freely move up and down with the high lobe without affecting the rocker arm. When the engine is operating below 6000-7000 rpm (dependent on year, car, and ECU installed), the lower lobe is operating the rocker arm and thus the valves, and the slipper-follower is freewheeling next to the rocker arm. When the engine is operating above the lift engagement point, the ECU activates an oil pressure switch which pushes a sliding pin under the slipper-follower on each rocker arm. The rocker arm is now locked into the slipper-follower's movements and thus follows the movement of the high rpm cam lobe and will operate with the high rpm cam profile until the pin is disengaged by the ECU. The lift system is similar in principle to Honda's VTEC operation.


title: VVT-i

text: The system was first introduced in the 2ZZ-GE found in the 1999 Toyota Celica. Toyota has ceased production of its VVTL-i engines for most markets, because the engine does not meet Euro IV specifications for emissions. As a result, this system has been discontinued on some Toyota models, including the Corolla T-Sport (Europe), Corolla Sportivo (Australia), Celica, Corolla XRS, Matrix XRS, and the Pontiac Vibe GT, all of which had the "2ZZ-GE" engine fitted. The Lotus Elise continues to offer the "2ZZ-GE" and the "1ZZ-FE" engine, while the Exige offers the engine with a supercharger.


title: VVT-i

text: The Dual VVT-i system adjusts timing on both intake and exhaust camshafts. It was first introduced in 1998 on the RS200 Altezza's 3S-GE engine. Dual VVT-i is also found in Toyota's 3.5-litre 2GR-FE V6 engine, first appearing on the 2005 Avalon. This engine can be found on numerous Toyota and Lexus models.


title: VVT-i

text: By adjusting the valve timing, engine start and stop occurs almost unnoticeably at minimum compression. Fast heating of the catalytic converter to its light-off temperature is possible, thereby reducing hydrocarbon emissions considerably.


title: VVT-i

text: Most Toyota engines including the 1LR-GUE (V10, used in the Lexus LFA), UR engines (V8), GR engines (V6), AR engines (large I4), ZR engines (medium I4), and NR engines (small I4) use this technology.


title: VVT-i

text: VVT-iE (Variable Valve Timing - intelligent by Electric motor) is a version of Dual VVT-i that uses an electrically operated actuator to adjust and maintain intake camshaft timing. The exhaust camshaft timing is still controlled using a hydraulic actuator. This form of variable valve timing technology was developed initially for Lexus vehicles. This system was first introduced on the 1UR-FSE engine in the 2007 Lexus LS 460.


title: VVT-i

text: The electric motor in the actuator spins together with the intake camshaft as the engine runs. To maintain camshaft timing, the actuator motor will operate at the same speed as the camshaft. To advance the camshaft timing, the actuator motor will rotate slightly faster than the camshaft speed. To retard camshaft timing, the actuator motor will rotate slightly slower than camshaft speed. The speed difference between the actuator motor and camshaft timing is used to operate a mechanism that varies the camshaft timing. The benefit of the electric actuation is enhanced response and accuracy at low engine speeds and at lower temperatures as well as a greater total range of adjustment. The combination of these factors allows more precise control, resulting in an improvement of both fuel economy, engine output and emissions performance.


title: VVT-i

text: VVT-iW (Variable Valve Timing - intelligent Wide) was introduced with the 2.0L turbocharged direct-injected 8AR-FTS fitted to the Lexus NX 200t. VVT-iW uses VVT-iW on the intake valves and VVT-i on the exhaust valves. The intake cam has mid-position cam lock mechanism that retards the continuously variable timing. It offers expanded valve opening angles (Wide) which enables the engine to operate in a modified-Atkinson cycle at low rpm for improved economy and lower emissions, and in the Otto cycle at high rpm for better performance, while delivering high torque throughout the rpm band.


title: VVT-i

text: The Valvematic system offers continuous adjustment to valve lift and timing and improves fuel efficiency by controlling the fuel/air intake using valve control rather than conventional throttle plate control. The technology made its first appearance in 2007 with the 3ZR-FAE engine in the Noah and later in early-2009 in the Avensis. This system is simpler in design compared to Valvetronic and VVEL, allowing the cylinder head to remain at the same height.


title: VVT-i

text: In 2010, Toyota USA announced a "Limited Service Campaign (LSC 90K)" to replace the rubber portion of the oil supply hose for the VVT-i actuator on the 2GR-FE (V6) engine, which were found to be defective. In all, approximately 1.6 million vehicles manufactured prior to 2008 were affected. The defective oil supply hoses were prone to degradation and eventual rupture, causing oil to rapidly leak and resulting in permanent engine damage.


title: VVT-i

text: In 2014, the LSC 90K Campaign was extended to 31 December 2021 on 117,500 Toyota brand vehicles that were "missed" during the initial campaign.


title: Zach Roerig

text: Zachary George Roerig (born February 22, 1985) is an American actor, known for his roles as Casey Hughes on "As the World Turns", Hunter Atwood on "One Life to Live" and Matt Donovan on "The Vampire Diaries".


title: Zach Roerig

text: Roerig was born in Montpelier, Ohio, to Andrea (b. 1963-2020) and Daniel Roerig (1961-2007). He has a younger sister, Emily, who was born in 1989. Roerig attended the Barbizon Modeling and Acting School in Cleveland and went on to participate in the International Modeling and Talent Association where he signed with his late talent manager. He graduated from Montpelier High School where he was both a football player and a wrestler. While he was growing up, Roerig worked for his father and grandfather at Fackler Monuments making gravestones. Shortly after graduating high school, Roerig moved to New York City to pursue his acting career.


title: Zach Roerig

text: Roerig played the role of Casey Hughes on "As the World Turns" from January 18, 2005 to May 2, 2007. Casey was the son of legacy couple Tom and Margo Hughes and, during his time, Casey was part of a popular couple with Alexandra Chando. After his departure, Roerig accepted a role on the soap "One Life to Live", as Hunter Atwood. He departed again later that year. Roerig then made a few appearances on "Friday Night Lights" as Cash the cowboy. From 2009 to 2017, he portrayed Matt Donovan in "The Vampire Diaries". He has made appearances on The Originals as his character, Matt Donovan, on Marvel's "The Gifted" as Pulse (Augustus), and on the big screen as Carter in "Rings". Zach plays young Ray Mott in "The Last Full Measure".


title: Zach Roerig

text: Roerig has a daughter who was born in January 2011. In June 2013, Roerig filed legal papers in Georgia, seeking full custody of his daughter after her mother, Roerig's ex-girlfriend Alana Turner, was incarcerated in a federal prison. On May 24, 2020, he was arrested for driving under the influence in Montpelier, Ohio, and was arraigned on June 4 of the same year.


title: Fireteam

text: A fireteam or fire team is a small military sub-subunit of infantry designed to optimize "bounding overwatch" and "fire and movement" tactical doctrine in combat. Depending on mission requirements, a typical fireteam consists of four or fewer members: an automatic rifleman, a grenadier, a rifleman, and a designated team leader. The role of each fireteam leader is to ensure that the fireteam operates as a cohesive unit. Two or three fireteams are organized into a section or squad in co-ordinated operations, which is led by a squad leader. Historically, nations with effective fireteam organization have had a significantly better performance from their infantry units in combat than those limited to operations by traditionally larger units.


title: Fireteam

text: US Army doctrine recognizes the fire team, or crew, as the smallest military organization while NATO doctrine refers to this level of organization simply as team. Fireteams are the most basic organization upon which modern infantry units are built in the British Army, Royal Air Force Regiment, Royal Marines, United States Army, United States Marine Corps, United States Air Force Security Forces, Canadian Forces, and Australian Army.


title: Fireteam

text: The concept of the fireteam is based on the need for tactical flexibility in infantry operations. A fireteam is capable of autonomous operations as part of a larger unit. Successful fireteam employment relies on quality small unit training for soldiers, experience of fireteam members operating together, sufficient communications infrastructure, and a quality non-commissioned officer corps to provide tactical leadership for the team.


title: Fireteam

text: These requirements have led to successful use of the fireteam concept by more professional militaries. It is less useful for armies employing massed infantry formations, or with significant conscription. Conscription makes fireteam development difficult, as team members are more effective as they build experience over time working together and building personal bonds.


title: Fireteam

text: In combat, while attacking or maneuvering, a fireteam generally spreads over a distance of , while in defensive positions the team can cover up to the range of its weapons or the limits of visibility, whichever is less. In open terrain, up to can be covered by an effective team, although detection range limits effectiveness beyond or so without special equipment. A team is effective so long as its primary weapon remains operational.


title: Fireteam

text: In the Canadian Army 'fireteam' refers to two soldiers paired for fire and movement. Two fireteams form an 'assault group' which is analogous to most other militaries' understanding of a fireteam; two assault groups and a vehicle group of one driver and one gunner form a section of ten soldiers.


title: Fireteam

text: People's Liberation Army forces traditionally used a three-man 'cell' (equivalent to fireteam) as the smallest military formation and such organization was widely employed throughout the Second Sino-Japanese War, Chinese Civil War, Korean War, Sino-Indian War, as well as Sino-Vietnamese War. It's unofficially named as "Three-three Organization". （）


title: Fireteam

text: In Chinese sources, this tactic is referred to as "three-three fireteams," after the composition of the attack: three men would form one fireteam, and three fireteams one squad. A Chinese platoon, consisting of 50 men, would form three ranks of such fireteams, which would be employed to attack "one point" from "two sides." With each cell carries at least one automatic weapon (In Korean War, it was submachine guns or light machine guns. In early to mid cold war, it was assault rifles or squad automatic weapons), while the rest carry bolt-action rifle or semiautomatic rifle so that each "cell" may independently fire and maneuver.


title: Fireteam

text: The French section ("groupe de combat" – "combat group") is divided into two teams. The "fire team" ("équipe de feu") is based around the section-level automatic rifle or light machine gun. The "shock team" ("équipe de choc"), made up of riflemen armed with rifle grenades or disposable rocket launchers, is the reconnaissance and maneuver unit. The teams employ bounding overwatch, with one element covering as the other moves. The team leaders have handheld radios so the elements can stay in contact with each other, as well as with the section leader's backpack radio set. The most common symbol of the modern French junior NCO ("chef d'équipe") has been a radio hanging around their neck.


title: Fireteam

text: Infantry units of the British Army, Royal Marines and RAF Regiment introduced the fireteam concept following the adoption of the SA80 rifle and light support weapon. An infantry section of eight men contains two fireteams, Charlie and Delta, each comprising an NCO (Corporal or Lance Corporal) and three privates.


title: Fireteam

text: The fireteam is generally used as a subdivision of the section for fire and maneuver rather than as a separate unit in its own right, although fireteams or fireteam-sized units are often used for reconnaissance tasks, special operations, and urban patrols (usually being to referred to as a 'brick' in the latter scenario).


title: Fireteam

text: In a Stryker Brigade Combat Team (SBCT)'s infantry rifle companies, one man in each rifle squad fireteam is either the squad anti-armour specialist (RMAT) armed with the FGM-148 Javelin, or the squad designated marksman (DM) who carries the M4 carbine and M14 rifle. In both cases, these two positions replace the basic rifleman of the standard rifle squad.


title: Fireteam

text: The United States Marine Corps doctrine dictates that any active fireteam will include at least one 2-man gunnery-team and summarizes its fireteam organization with the mnemonic "ready-team-fire-assist", the following being the arrangement of the fireteam when in a column:


title: Fireteam

text: Navy Construction Force, "Seabee" Construction Battalions, utilize fireteams (as well as companies, platoons, and squads), similar in size to those employed by the USMC, in their organizational structure. Seabee units may be attached to Marine Corps units.


title: Fireteam

text: Many other armed forces see the squad as the smallest military unit; some countries' armies have a pair consisting of two soldiers as the smallest military unit. In others a fireteam is composed of two pairs of soldiers (fire and manuever team) forming a fireteam. Vietnamese communist forces, who received extensive advisory support from Chinese communists, also adopted a fireteam concept similar to that of Chinese, known as "tam tam chế." and such organization is still in use nowadays.


title: Fireteam

text: Fireteams have their origins in the early 20th century. From the Napoleonic Wars until World War I, military tactics involved central control of large numbers of soldiers in mass formation where small units were given little initiative.


title: Fireteam

text: Groups of four soldiers were mainly employed for guard duty. In the Roman Army they were referred to as "quaternio" (Greek τετράδιον).


title: Fireteam

text: Skirmishers in the Napoleonic War would often work in teams of two, ranging ahead of the main group and providing covering fire for each other.


title: Fireteam

text: During World War I, trench warfare resulted in a stalemate on the Western Front. In order to combat this stalemate, the Germans developed a doctrinal innovation known as infiltration tactics (based on the Russian tactics used in the Brusilov Offensive), in which a brief intensive artillery preparation would be followed by small, autonomous teams of stormtroopers, who would covertly penetrate defensive lines. The Germans used their stormtroopers organized into squads at the lowest levels to provide a cohesive strike force in breaking through Allied lines. The British and Canadian troops on the Western Front started dividing platoons into sections after the Battle of the Somme in 1916. (This idea was later further developed in World War II). French Chasseur units in WWI were organized into fireteams, equipped with a light machine gun (Chauchat) team and grenades, to destroy German fire positions by fire (not assault) at up to 200 meters using rifle grenades. The light machine gun team would put suppressive fire on the enemy position, while the grenadier team moved to a position where the enemy embrasure could be attacked with grenades. The Chasseur tactics were proven during the Petain Offensive of 1917. Survivors of these French Chasseur units taught these tactics to American infantry, who used them with effectiveness at St. Mihiel and the Argonne. It was typical of a fireteam in this era to consist of four infantrymen: two assaulters with carbines, one grenadier, and one sapper.


title: Fireteam

text: In the inter-war years, United States Marine Corps Captain Evans F. Carlson and Merritt A. Edson are believed to have developed the fireteam concept during the United States occupation of Nicaragua (1912–1933). At that time the US Marine squad consisted of a Corporal and seven Marines all armed with a bolt-action M1903 Springfield rifle and an automatic rifleman armed with a Browning Automatic Rifle. The introduction of the Thompson submachine gun and Winchester Model 1912 shotgun was popular with the Marines as a point-defense weapon for countering ambush by Nicaraguan guerrillas within the thick vegetation that could provide cover for a quick overrun of a patrol. A team of four men armed with these weapons had proven more effective in terms of firepower and maneuverability than the standard nine-man rifle squad.


title: Fireteam

text: Carlson, who later went to China in 1937 and observed Communist 8th Route Army units of the National Revolutionary Army in action against the Imperial Japanese Army, brought these ideas back to the US when the country entered World War II. Under his command, the 2nd Marine Raider battalion were issued with the semi-automatic M1 Garand rifle and were organized in the standard 4-man fireteam (although it was called firegroup) concept, 3 firegroups to a squad with a squad leader. A firegroup was composed of an M1 Garand rifleman, a BAR gunner and a submachine gunner. After sustaining severe wounds, Carlson was replaced and his battalion later disbanded and reorganized under conventional Marine doctrine of ten-man squads. Later, Carlson's fireteam concept was re-adopted.


title: Fireteam

text: WWII US Army rifle squads consisted of twelve soldiers divided into three teams: The A "Able" (contemporary spelling alphabet) team consisted of the squad leader and two scouts, the support B "Baker" team of the BAR gunner, assistant gunner, and ammunition bearer, and C "Charlie" team of the assistant squad leader, also serving as the anti-tank grenadier, and five riflemen, one of whom served as the alternate anti-tank grenadier). In an assault the A team would provide overwatch and security or assist the C team in the assault, as the squad leader directed, while the B team provided suppressive fire. Suppressive fire from the BAR would be supplemented by fire from the rifles of his team as he reloaded, and could be further supplemented by platoon medium machine guns.


title: Fireteam

text: The US Army Rangers and Special Service Force adopted an early fireteam concept when on campaign in Italy and France. Each squad sub-unit of 4 to 5 men was heavily armed, composed of a 2-man BAR automatic rifleman and assistant, a scout (marksman/grenadier) armed with a M1903 Springfield with a rifle grenade discharger, and a team leader armed with an M1 carbine or M1 Thompson submachine gun. Their later misuse as conventional infantry negated their special training and fighting skill and their use as "fire brigades" against larger enemy forces negated their advantages in aggressiveness and firepower.


title: Fireteam

text: Meanwhile, the Communist Chinese established the three-man fireteam concept as the three-man cell when they organized a regular army, and its organization seemed to have been disseminated throughout all of Asia's communist forces, perhaps the most famous of which are the PAVN/NVA (People's Army of Vietnam/North Vietnamese Army) and the Viet Cong.


title: Fireteam

text: A battle pair is the smallest unit above the individual soldier, in the modern era chiefly employed by Baltic militaries and special forces like the Special Air Service. It consists of two soldiers with one soldier acting as senior of the two fighters (decided amongst the two or by their superior). A fireteam in turn consists of at least two fire and maneuver teams, and a squad of two or more fireteams.


title: Fireteam

text: It may be known in the US as a Fire and Maneuver team. The concept is not widely utilized. The United States and most Commonwealth armies rely on the concept of fire teams forming a squad.


title: Fireteam

text: Until 2015 in the Finnish Defence Forces, three "taistelupari" (combat pairs) formed a squad along with a squad leader. A three-man fireteam is now the smallest standard unit in the Finnish infantry doctrine.


title: Fireteam

text: The French Army has the concept of a "binôme" ‘pair’. In the regular forces it is the pairing of an experienced soldier with a recruit or replacement. The new man learns from the experienced man how to properly perform the everyday tasks and responsibilities of his assignment.


title: Fireteam

text: In the old Colonial Forces (like the French Foreign Legion) it was a means of imposing order. The pair were responsible for each other – if one member broke the rules or deserted, the other would be punished for not preventing it.


title: Fireteam

text: According to the Swedish Armed Forces field manual, a "Stridspar" working in unison is as effective as four soldiers of same quality acting individually.


title: Trastuzumab

text: Trastuzumab, sold under the brand name Herceptin among others, is a monoclonal antibody used to treat breast cancer and stomach cancer. It is specifically used for cancer that is HER2 receptor positive. It may be used by itself or together with other chemotherapy medication. Trastuzumab is given by slow injection into a vein and injection just under the skin.


title: Trastuzumab

text: Common side effects include fever, infection, cough, headache, trouble sleeping, and rash. Other severe side effects include heart failure, allergic reactions, and lung disease. Use during pregnancy may harm the baby. Trastuzumab works by binding to the HER2 receptor and slowing down cell replication.


title: Trastuzumab

text: Trastuzumab was approved for medical use in the United States in September 1998, and in the European Union in August 2000. It is on the World Health Organization's List of Essential Medicines. A biosimilar was approved in the European Union in November 2017, and in the United States in December 2018.


title: Trastuzumab

text: The safety and efficacy of trastuzumab-containing combination therapies (with chemotherapy, hormone blockers, or lapatinib) for the treatment of metastatic breast cancer. The overall hazard ratios (HR) for overall survival and progression free survival were 0.82 and 0.61, respectively. It was difficult to accurately ascertain the true impact of trastuzumab on survival, as in three of the seven trials, over half of the patients in the control arm were allowed to cross-over and receive trastuzumab after their cancer began to progress. Thus, this analysis likely underestimates the true survival benefit associated with trastuzumab treatment in this population. In these trials, trastuzumab also increased the risk of heart problems, including heart failure and left ventricular ejection fraction decline.


title: Trastuzumab

text: In early-stage HER2-positive breast cancer, trastuzumab-containing regimens improved overall survival (Hazard ratio (HR) = 0.66) and disease-free survival (HR = 0.60). Increased risk of heart failure (RR = 5.11) and decline in left ventricular ejection fraction (relative risk RR = 1.83) were seen in these trials as well. Two trials involving shorter term treatment with trastuzumab did not differ in efficacy from longer trials, but produced less cardiac toxicity.


title: Trastuzumab

text: The original studies of trastuzumab showed that it improved overall survival in late-stage (metastatic) HER2-positive breast cancer from 20.3 to 25.1 months. In early-stage HER2-positive breast cancer, it reduces the risk of cancer returning after surgery. The absolute reduction in the risk of cancer returning within three years was 9.5%, and the absolute reduction in the risk of death within 3 years was reduced by 3%. However, it increases serious heart problems by an absolute risk of 2.1%, though the problems may resolve if treatment is stopped.


title: Trastuzumab

text: Trastuzumab has had a "major impact in the treatment of HER2-positive metastatic breast cancer." The combination of trastuzumab with chemotherapy has been shown to increase both survival and response rate, in comparison to trastuzumab alone.


title: Trastuzumab

text: It is possible to determine the "erbB2 status" of a tumor, which can be used to predict efficacy of treatment with trastuzumab. If it is determined that a tumor is overexpressing the erbB2 oncogene and the patient has no significant pre-existing heart disease, then a patient is eligible for treatment with trastuzumab. It is surprising that although trastuzumab has great affinity for HER2 and high doses can be administered (because of its low toxicity), 70% of HER2+ patients do not respond to treatment. In fact resistance to the treatment develops rapidly, in virtually all patients. A mechanism of resistance involves failure to downregulate p27 (Kip1) as well as suppressing p27 translocation to the nucleus in breast cancer, enabling cdk2 to induce cell proliferation.


title: Trastuzumab

text: In May 2021, the FDA approved pembrolizumab in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of people with locally advanced unresectable or metastatic HER2 positive gastric or gastroesophageal junction (GEJ) adenocarcinoma.


title: Trastuzumab

text: The optimal duration of add-on trastuzumab treatment after surgery for early breast cancer is unknown. One year of treatment is generally accepted based on clinical trial evidence that demonstrated the superiority of one-year treatment over none. However, a small Finnish trial also showed similar improvement with nine weeks of treatment over no therapy. Because of the lack of direct head-to-head comparison in clinical trials, it is unknown whether a shorter duration of treatment may be just as effective (with fewer side effects) than the accepted practice of treatment for one year. Debate about treatment duration has become a relevant issue for many public health policy makers because administering trastuzumab for a year is very expensive. Consequently, some countries with a taxpayer-funded public health system, such as New Zealand, chose to fund limited adjuvant therapy. However, subsequently New Zealand has revised its policy and now funds trastuzumab treatment for up to 12 months.


title: Trastuzumab

text: Some of the common side effects of trastuzumab are flu-like symptoms (such as fever, chills and mild pain), nausea and diarrhea.


title: Trastuzumab

text: One of the more serious complications of trastuzumab is its effect on the heart, although this is rare. In 2-7% of cases, trastuzumab is associated with cardiac dysfunction, which includes congestive heart failure. As a result, regular cardiac screening with either a MUGA scan or echocardiography is commonly undertaken during the trastuzumab treatment period. The decline in ejection fraction appears to be reversible.


title: Trastuzumab

text: Trastuzumab downregulates neuregulin-1 (NRG-1), which is essential for the activation of cell survival pathways in cardiomyocytes and the maintenance of cardiac function. NRG-1 activates the MAPK pathway and the PI3K/AKT pathway as well as focal adhesion kinases (FAK). These are all significant for the function and structure of cardiomyocytes. Trastuzumab can therefore lead to cardiac dysfunction.


title: Trastuzumab

text: Approximately 10% of people are unable to tolerate the drug because of pre-existing heart problems; physicians are balancing the risk of recurrent cancer against the higher risk of death due to cardiac disease in this population. The risk of cardiomyopathy is increased when trastuzumab is combined with anthracycline chemotherapy (which itself is associated with cardiac toxicity).


title: Trastuzumab

text: Women having periods (or whose periods stopped due to chemotherapy) may need to use barrier contraception (such as condoms) while taking trastuzumab, and for at least six months afterwards. This is because of the possibility of harming a developing fetus.


title: Trastuzumab

text: The "HER2" gene (also known as "HER2/neu" and "ErbB2" gene) is amplified in 20–30% of early-stage breast cancers. Trastuzumab is a monoclonal antibody targeting HER2, inducing an immune-mediated response that causes internalization and recycling of HER2. It may also upregulate cell cycle inhibitors such as p21 and p27.


title: Trastuzumab

text: The HER2 pathway promotes cell growth and division when it is functioning normally; however, when it is overexpressed, cell growth accelerates beyond its normal limits. In some types of cancer, the pathway is exploited to promote rapid cell growth and proliferation and hence tumor formation. The EGF pathway includes the receptors HER1 (EGFR), HER2, HER3, and HER4; the binding of ligands (e.g. EGF etc.) to HER receptors is required to activate the pathway. The pathway initiates the MAP kinase pathway as well as the PI3 kinase/AKT pathway, which in turn activates the NF-κB pathway. In cancer cells the HER2 protein can be expressed up to 100 times more than in normal cells (2 million versus 20,000 per cell). This overexpression leads to strong and constant proliferative signaling and hence tumor formation. Overexpression of HER2 also causes deactivation of checkpoints, allowing for even greater increases in proliferation.


title: Trastuzumab

text: The HER receptors are proteins that are embedded in the cell membrane and communicate molecular signals from outside the cell (molecules called EGFs) to inside the cell, and turn genes on and off. The HER (human epidermal growth factor receptor) protein, binds to human epidermal growth factor, and stimulates cell proliferation. In some cancers, notably certain types of breast cancer, HER2 is over-expressed and causes cancer cells to reproduce uncontrollably.


title: Trastuzumab

text: HER2 is localized at the cell surface, and carries signals from outside the cell to the inside. Signaling compounds called mitogens (specifically EGF in this case) arrive at the cell membrane, and bind to the extracellular domain of the HER family of receptors. Those bound proteins then link (dimerize), activating the receptor. HER2 sends a signal from its intracellular domain, activating several different biochemical pathways. These include the PI3K/Akt pathway and the MAPK pathway. Signals on these pathways promote cell proliferation and the growth of blood vessels to nourish the tumor (angiogenesis). ERBB2 is the preferred dimerization partner for the other family members and ERBB2 heterodimers signaling is stronger and longer acting compared to heterodimers between other ERBB members. It has been reported that Trastuzumab induces the formation of complementarity-determining regions (CDRs) leading to surface redistribution of ERBB2 and EGFR in CDRs and that the ERBB2-dependent MAPK phosphorylation and EGFR/ERBB1 expression are both required for CDR formation. CDR formation requires activation of both the protein regulator of actin polymerization N-WASP, mediated by ERK1/2, and of the actin-depolymerizing protein cofilin, mediated by EGFR/ERBB1. Furthermore, this latter event may be inhibited by the negative cell motility regulator p140Cap, as we found that p140Cap overexpression led to cofilin deactivation and inhibition of CDR formation.


title: Trastuzumab

text: Normal cell division—mitosis—has checkpoints that keep cell division under control. Some of the proteins that control this cycle are called cdk2 (CDKs). Overexpression of HER2 sidesteps these checkpoints, causing cells to proliferate in an uncontrolled fashion. This is caused by phosphorylation by Akt.


title: Trastuzumab

text: Trastuzumab binds to domain IV of the extracellular segment of the HER2/neu receptor. Monoclonal antibodies that bind to this region have been shown to reverse the phenotype of HER2/neu expressing tumor cells. Cells treated with trastuzumab undergo arrest during the G1 phase of the cell cycle so there is reduced proliferation. It has been suggested that trastuzumab does not alter HER-2 expression, but downregulates activation of AKT. In addition, trastuzumab suppresses angiogenesis both by induction of antiangiogenic factors and repression of proangiogenic factors. It is thought that a contribution to the unregulated growth observed in cancer could be due to proteolytic cleavage of HER2/neu that results in the release of the extracellular domain. One of the most relevant proteins that trastuzumab activates is the tumor suppressor p27 (kip1), also known as CDKN1B. Trastuzumab has been shown to inhibit HER2/neu ectodomain cleavage in breast cancer cells.


title: Trastuzumab

text: Experiments in laboratory animals indicate that antibodies, including trastuzumab, when bound to a cell, induce immune cells to kill that cell, and that such antibody-dependent cell-mediated cytotoxicity is another important mechanism of action.


title: Trastuzumab

text: Trastuzumab inhibits the effects of overexpression of HER2. If the breast cancer does not overexpress HER2, trastuzumab will have no beneficial effect (and may cause harm). Doctors use laboratory tests to discover whether HER2 is overexpressed. In the routine clinical laboratory, the most commonly employed methods for this are immunohistochemistry (IHC) and either silver, chromogenic or fluorescent in situ hybridisation (SISH/CISH/FISH). HER2 amplification can be detected by virtual karyotyping of formalin-fixed paraffin embedded tumor. Virtual karyotyping has the added advantage of assessing copy number changes throughout the genome, in addition to detecting HER-2 amplification (but not overexpression). Numerous PCR-based methodologies have also been described in the literature. It is also possible to estimate "HER2" copy number from microarray data.


title: Trastuzumab

text: There are two FDA-approved commercial kits available for HER2 IHC; Dako HercepTest and Ventana Pathway. These are highly standardised, semi-quantitative assays which stratify expression levels into; 0 (<20,000 receptors per cell, no visible expression), 1+ (~100,000 receptors per cell, partial membrane staining, < 10% of cells overexpressing HER-2), 2+ (~500,000 receptors per cell, light to moderate complete membrane staining, > 10% of cells overexpressing HER-2), and 3+ (~2,000,000 receptors per cell, strong complete membrane staining, > 10% of cells overexpressing HER-2). The presence of cytoplasmic expression is disregarded. Treatment with trastuzumab is indicated in cases where HER2 expression has a score of 3+. However, IHC has been shown to have numerous limitations, both technical and interpretative, which have been found to impact on the reproducibility and accuracy of results, especially when compared with ISH methodologies. It is also true, however, that some reports have stated that IHC provides excellent correlation between gene copy number and protein expression.


title: Trastuzumab

text: Fluorescent in situ hybridization (FISH) is viewed as being the "gold standard" technique in identifying patients who would benefit from trastuzumab, but it is expensive and requires fluorescence microscopy and an image capture system. The main expense involved with CISH is in the purchase of FDA-approved kits, and as it is not a fluorescent technique it does not require specialist microscopy and slides may be kept permanently. Comparative studies of CISH and FISH have shown that these two techniques show excellent correlation. The lack of a separate chromosome 17 probe on the same section is an issue with regards to acceptance of CISH. As of June 2011 Roche has obtained FDA approval for the INFORM HER2 Dual ISH DNA Probe cocktail developed by Ventana Medical Systems. The DDISH (Dual-chromagen/Dual-hapten In-situ hybridization) cocktail uses both HER2 and Chromosome 17 hybridization probes for chromagenic visualization on the same tissue section. The detection can be achieved by using a combination of ultraView SISH(silver in-situ hybridization) and ultraView Red ISH for deposition of distinct chromgenic precipitates at the site of DNP or DIG labeled probes.


title: Trastuzumab

text: The recommended assays are a combination of IHC and FISH, whereby IHC scores of 0 and 1+ are negative (no trastuzumab treatment), scores of 3+ are positive (trastuzumab treatment), and score of 2+ (equivocal case) is referred to FISH for a definitive treatment decision. Industry best practices indicate the use of FDA-cleared Automated Tissue Image Systems by laboratories for automated processing of specimens, thereby reducing process variability, avoiding equivocal cases, and ensuring maximum efficacy of trastuzumab therapy.


title: Trastuzumab

text: One of the challenges in the treatment of breast cancer patients by herceptin is our understanding towards herceptin resistance. In the last decade, several assays have been performed to understand the mechanism of Herceptin resistance with/without supplementary drugs. Recently, all this information has been collected and compiled in form of a database HerceptinR. This database HerceptinR is a collection of assays performed to test sensitivity or resistance of Herceptin Antibodies towards breast cancer cell lines. This database provides comprehensive information about experimental data perform to understanding factors behind herceptin resistance as well as assays performed for improving Herceptin sensitivity with the help of supplementary drugs. This is the first database developed to understand herceptin resistance that can be used for designing herceptin sensitive biomarkers.


title: Trastuzumab

text: The drug was first discovered by scientists including Dr. Axel Ullrich and Dr. H. Michael Shepard at Genentech, Inc. in South San Francisco, CA. Earlier discovery about the "neu" oncogene by Robert Weinberg's lab and the monoclonal antibody recognizing the oncogenic receptor by Mark Greene's lab also contributed to the establishment of HER2 targeted therapies. Dr. Dennis Slamon subsequently worked on trastuzumab's development. A book about Dr. Slamon's work was made into a television film called "Living Proof", that premiered in 2008. Genentech developed trastuzumab jointly with UCLA, beginning the first clinical trial with 15 women in 1992. By 1996, clinical trials had expanded to over 900 women, but due to pressure from advocates based on early success, Genentech worked with the FDA to begin a lottery system allowing 100 women each quarter access to the medication outside the trials. Herceptin was Fast-tracked by the FDA and gained approval in September 1998.


title: Trastuzumab

text: Biocon Ltd and its partner Mylan obtained regulatory approval to sell a biosimilar in 2014, but Roche contested the legality of the approval; that litigation ended in 2016, and Biocon and Mylan each introduced their own branded biosimilars.


title: Trastuzumab

text: Trastuzumab costs about for a full course of treatment, Trastuzumab brought in $327 million in revenue for Genentech in the fourth quarter of 2007.


title: Trastuzumab

text: Since October 2006, trastuzumab has been made available for Australian women and men with early-stage breast cancer via the Pharmaceutical Benefits Scheme. This is estimated to cost the country over A$470 million for 4–5 years supply of the drug.


title: Trastuzumab

text: Roche has agreed with Emcure in India to make an affordable version of this cancer drug available to the Indian market.


title: Trastuzumab

text: Roche has changed the brand name of the drug and has re-introduced an affordable version of the same in the Indian market. The new drug named Herclon would cost approximately RS75,000 INR (1,200) in the Indian market.


title: Trastuzumab

text: On September 16, 2014, Genentech notified hospitals in the United States that, as of October, trastuzumab could only be purchased through their selected specialty drugs distributors not through the usual general line wholesalers. By being forced to purchase through specialty pharmacies, hospitals lost rebates from the big wholesalers and the ability to negotiate cost-minus discounts with their wholesalers.


title: Trastuzumab

text: By 2014, around 20 companies, particularly from emerging markets, were developing biosimilar versions of trastuzumab


title: Trastuzumab

text: after Roche/Genentech's patents expired in 2014 in Europe, and in 2019 in the United States. In 2013, Roche/Genentech relinquished its patent right for the drug in India because of the difficult IP environment there.


title: Trastuzumab

text: In January 2015, BIOCAD announced the first trastuzumab biosimilar approved by the Ministry of Health of the Russian Federation. Iran also approved its own version of the monoclonal antibody in January 2016, as AryoTrust, and announced its readiness to export the drug to other countries in the Middle-East and Central Asia when trade sanctions were lifted.


title: Trastuzumab

text: In 2016, the investigational biosimilar MYL-1401O has shown comparable efficacy and safety to the Herceptin branded trastuzumab.


title: Trastuzumab

text: Trastuzumab-dkst (Ogivri, Mylan GmbH) was approved in the United States in December 2017, to "treat patients with breast cancer or gastric or gastroesophageal junction adenocarcinoma whose tumors overexpress the HER-2 gene." Ogivri was approved for medical use in the European Union in December 2018.


title: Trastuzumab

text: In November 2017, the European Commission approved Ontruzant, a biosimilar-trastuzumab from Samsung Bioepis Co., Ltd, for the treatment of early breast cancer, metastatic breast cancer and metastatic gastric cancer. Ontruzant is the first trastuzumab biosimilar to receive regulatory approval in Europe.


title: Trastuzumab

text: Herzuma was approved for medical use in the European Union in February 2018. Herzuma, a trastuzumab biosimilar, was approved in the United States in December 2018. The approval was based on comparisons of extensive structural and functional product characterization, animal data, human pharmacokinetic, clinical immunogenicity, and other clinical data demonstrating that Herzuma is biosimilar to US Herceptin. Herzuma has been approved as a biosimilar, not as an interchangeable product.


title: Trastuzumab

text: Apart from the biosimilars noted above, trastuzumab is also a component of some antibody-drug conjugates, such as trastuzumab emtansine. Another ADC, trastuzumab deruxtecan was approved for use in the United States in December 2019.


title: Alhambra Decree

text: The Alhambra Decree (also known as the Edict of Expulsion; Spanish: "Decreto de la Alhambra", "Edicto de Granada") was an edict issued on 31 March 1492, by the joint Catholic Monarchs of Spain (Isabella I of Castile and Ferdinand II of Aragon) ordering the expulsion of practising Jews from the Crowns of Castile and Aragon and its territories and possessions by 31 July of that year. The primary purpose was to eliminate the influence of practising Jews on Spain's large formerly-Jewish "converso" New Christian population, to ensure the latter and their descendants did not revert to Judaism. Over half of Spain's Jews had converted as a result of the religious persecution and pogroms which occurred in 1391. Due to continuing attacks, around 50,000 more had converted by 1415. A further number of those remaining chose to convert to avoid expulsion. As a result of the Alhambra decree and persecution in the years leading up to the expulsion, of Spain's estimated 300,000 Jewish origin population, a total of over 200,000 had converted to Catholicism to remain in Spain, and between 40,000 and 100,000 remained Jewish and suffered expulsion. An unknown number of the expelled eventually succumbed to the pressures of life in exile away from formerly-Jewish relatives and networks back in Spain, and so converted to Catholicism to be allowed to return in the years following expulsion.


title: Alhambra Decree

text: The edict was formally and symbolically revoked on 16 December 1968, following the Second Vatican Council. This was a full century after Jews had been openly practicing their religion in Spain and synagogues were once more legal places of worship under Spain's Laws of Religious Freedom.


title: Alhambra Decree

text: In 1924, the regime of Primo de Rivera granted Spanish citizenship to a part of the Sephardic Jewish diaspora, though few people benefited from it in practice. In 2015, the government of Spain passed a law allowing dual citizenship to Jewish descendants who apply, to "compensate for shameful events in the country's past." Thus, Sephardi Jews who could prove that they are the descendants of those Jews expelled from Spain because of the Alhambra Decree would "become Spaniards without leaving home or giving up their present nationality." The Spanish law expired in 2019 and new applications for Spanish citizenship on the basis of Sephardic family heritage are no longer allowed. However, the descendants of the Jews exiled from the Iberian Peninsula may still apply for Portuguese citizenship.


title: Alhambra Decree

text: By the end of the eighth century, Muslim forces had conquered and settled most of the Iberian Peninsula. Under Islamic law, the Jews, who had lived in the region since at least Roman times, were considered "People of the Book," which was a protected status. Compared to the repressive policies of the Visigothic Kingdom, who, starting in the sixth century had enacted a series of anti-Jewish statutes which culminated in their forced conversion and enslavement, the tolerance of the Muslim Moorish rulers of "al-Andalus" allowed Jewish communities to thrive. Jewish merchants were able to trade freely across the Islamic world, which allowed them to flourish, and made Jewish enclaves in Muslim Iberian cities great centers of learning and commerce. This led to a flowering of Jewish culture, as Jewish scholars were able to gain favor in Muslim courts as skilled physicians, diplomats, translators, and poets. Although Jews never enjoyed equal status to Muslims, in some Taifas, such as Granada, Jewish men were appointed to very high offices, including Grand Vizier.


title: Alhambra Decree

text: The "Reconquista", or the gradual reconquest of Muslim Iberia by the Christian kingdoms in the North, was driven by a powerful religious motivation: to reclaim Iberia for Christendom following the Umayyad conquest of Hispania centuries before. By the fourteenth century, most of the Iberian Peninsula (present-day Spain and Portugal) had been reconquered by the Christian kingdoms of Castile, Aragon, León, Galicia, Navarre, and Portugal.


title: Alhambra Decree

text: During the Christian re-conquest, the Muslim kingdoms in Spain became less welcoming to the "dhimmi". In the late twelfth century, the Muslims in al-Andalus invited the fanatical Almohad dynasty from North Africa to push the Christians back to the North. After they gained control of the Iberian Peninsula, the Almohads offered the Sephardim a choice between expulsion, conversion, and death. Many Jewish people fled to other parts of the Muslim world, and also to the Christian kingdoms, which initially welcomed them. In Christian Spain, Jews functioned as courtiers, government officials, merchants, and moneylenders. Therefore, the Jewish community was both useful to the ruling classes and to an extent protected by them.


title: Alhambra Decree

text: As the Reconquista drew to a close, overt hostility against Jews in Christian Spain became more pronounced, finding expression in brutal episodes of violence and oppression. In the early fourteenth century, the Christian kings vied to prove their piety by allowing the clergy to subject the Jewish population to forced sermons and disputations. More deadly attacks came later in the century from mobs of angry Catholics, led by popular preachers, who would storm into the Jewish quarter, destroy synagogues, and break into houses, forcing the inhabitants to choose between conversion and death. Thousands of Jews sought to escape these attacks by converting to Christianity. These Jewish converts were commonly called "conversos", New Christians, or "marranos"; the latter two terms were used as insults. At first, these conversions seemed an effective solution to the cultural conflict: many "converso" families met with social and commercial success. But eventually their success made these new Catholics unpopular with their neighbors, including some of the clergy of the Church and Spanish aristocrats competing with them for influence over the royal families. By the mid-fifteenth century, the demands of the Old Christians that the Catholic Church and the monarchy differentiate them from the conversos led to the first "limpieza de sangre" laws, which restricted opportunities for converts.


title: Alhambra Decree

text: These suspicions on the part of Christians were only heightened by the fact that some of the coerced conversions were undoubtedly insincere. Some, but not all, "conversos" had understandably chosen to salvage their social and commercial positions or their lives by the only option open to them – baptism and embrace of Christianity – while privately adhering to their Jewish practice and faith. Recently converted families who continued to intermarry were especially viewed with suspicion. These secret practitioners are commonly referred to as crypto-Jews or "marranos".


title: Alhambra Decree

text: The existence of crypto-Jews was a provocation for secular and ecclesiastical leaders who were already hostile toward Spain's Jewry. For their part, the Jewish community viewed conversos with compassion, because Jewish law held that conversion under threat of violence was not necessarily legitimate. Although the Catholic Church was also officially opposed to forced conversion, under ecclesiastical law all baptisms were lawful, and once baptized, converts were not allowed to rejoin their former religion. The uncertainty over the sincerity of Jewish converts added fuel to the fire of antisemitism in fifteenth-century Spain.