title: American Zoetrope

text: The neighborhood is well known for its cafes and its writers. Coppola wrote much of the screenplay for "The Godfather" in the nearby Caffe Trieste and Lawrence Ferlinghetti's City Lights Books is located up Columbus Avenue from the Sentinel Building.


title: Kurt Weill

text: Kurt Julian Weill (March 2, 1900April 3, 1950) was a German-born American composer active from the 1920s in his native country, and in his later years in the United States. He was a leading composer for the stage who was best known for his fruitful collaborations with Bertolt Brecht. With Brecht, he developed productions such as his best-known work, "The Threepenny Opera", which included the ballad "Mack the Knife". Weill held the ideal of writing music that served a socially useful purpose, "Gebrauchsmusik". He also wrote several works for the concert hall and a number of works on Jewish themes. He became a United States citizen on August 27, 1943.


title: Kurt Weill

text: Weill was born on March 2, 1900, the third of four children to Albert Weill (1867–1950) and Emma Weill (née Ackermann; 1872–1955). He grew up in a religious Jewish family in the "Sandvorstadt", the Jewish quarter in Dessau in Saxony, where his father was a cantor. At the age of twelve, Weill started taking piano lessons and made his first attempts at writing music; his earliest preserved composition was written in 1913 and is titled "Mi Addir: Jewish Wedding Song".


title: Kurt Weill

text: In 1915, Weill started taking private lessons with Albert Bing, kapellmeister at the "Herzogliches Hoftheater zu Dessau", who taught him piano, composition, music theory, and conducting. Weill performed publicly on piano for the first time in 1915, both as an accompanist and soloist. The following years he composed numerous lieder to the lyrics of poets such as Joseph von Eichendorff, Arno Holz, and Anna Ritter, as well as a cycle of five songs titled "Ofrahs Lieder" to a German translation of a text by Yehuda Halevi.


title: Kurt Weill

text: Weill graduated with an Abitur from the "Oberrealschule" of Dessau in 1918, and enrolled at the Berliner Hochschule für Musik at the age of 18, where he studied composition with Engelbert Humperdinck, conducting with Rudolf Krasselt, and counterpoint with Friedrich E. Koch, and also attended philosophy lectures by Max Dessoir and Ernst Cassirer. The same year, he wrote his first string quartet (in B minor).


title: Kurt Weill

text: Weill's family experienced financial hardship in the aftermath of World War I, and in July 1919, Weill abandoned his studies and returned to Dessau, where he was employed as a répétiteur at the Friedrich-Theater under the direction of the new Kapellmeister, Hans Knappertsbusch. During this time, he composed an orchestral suite in E-flat major, a symphonic poem on Rainer Maria Rilke's "The Lay of the Love and Death of Cornet Christopher Rilke", and "Schilflieder" ("Reed Songs"), a cycle of five songs to poems by Nikolaus Lenau. In December 1919, through the help of Humperdinck, Weill was appointed as Kapellmeister at the newly founded Stadttheater in Lüdenscheid, where he directed opera, operetta, and singspiel for five months. He subsequently composed a cello sonata and "Ninon de Lenclos", a now lost one-act operatic adaptation of a 1905 play by Ernst Hardt. From May to September 1920, Weill spent a few months in Leipzig, where his father had become the director of a Jewish orphanage. Before he returned to Berlin, in September 1920, he composed "Sulamith", a choral fantasy for soprano, female choir, and orchestra.


title: Kurt Weill

text: Back in Berlin, Weill had an interview with Ferruccio Busoni in December 1920. After examining some of Weill's compositions, Busoni accepted him as one of five master students in composition at the Preussische Akademie der Künste in Berlin.


title: Kurt Weill

text: From January 1921 to December 1923, Weill studied music composition with him and also counterpoint with Philipp Jarnach in Berlin. During his first year he composed his first symphony, "Sinfonie in einem Satz", as well as the lieder "Die Bekehrte" (Goethe) and two "Rilkelieder" for voice and piano. Busoni, then approaching the end of his life, was a major influence on Weill. Where Weill's early compositions reflect the post-Wagnerian Romanticism and Expressionism common in German classical music of that era, Busoni was a Neoclassicist. Busoni's influence can be seen especially in Weill's vocal and stage works, which moved steadily away from having the music reflect the characters' emotions to have it function as (often ironic) commentary. This was Weill's own path to some of the same notions of Epic theater and the "Verfremdungseffekt" (distancing effect) advocated by his future collaborator Brecht.


title: Kurt Weill

text: To support his family in Leipzig, Weill also worked as a pianist in a Bierkeller tavern. In 1922, Weill joined the November Group's music faction. That year he composed a psalm, a divertimento for orchestra, and "Sinfonia Sacra: Fantasia, Passacaglia, and Hymnus for Orchestra". On November 18, 1922, his children's pantomime "Die Zaubernacht" ("The Magic Night") premiered at the Theater am Kurfürstendamm; it was the first public performance of any of Weill's works in the field of musical theatre.


title: Kurt Weill

text: Out of financial need, Weill taught music theory and composition to private students from 1923 to 1925. Among his students were Claudio Arrau, Maurice Abravanel, Heinz Jolles (later known as Henry Jolles), Nikos Skalkottas, and Esther Zweig. Arrau, Abravanel, and Jolles remained members of Weill's circle of friends thereafter, and Jolles's sole surviving composition predating the rise of the Nazi regime in 1933 is a fragment of a work for four pianos he and Weill wrote jointly.


title: Kurt Weill

text: Weill's compositions during his last year of studies included "Quodlibet", an orchestral suite version of "Die Zaubernacht"; "Frauentanz", seven medieval poems for soprano, flute, viola, clarinet, French horn, and bassoon; and "Recordare" for choir and children's choir to words from the Book of Lamentations. Further premieres that year included a performance of his "Divertimento for Orchestra" by the Berlin Philharmonic under the direction of Heinz Unger on April 10, 1923, and the Hindemith-Amar Quartet's rendering of Weill's "String Quartet", Op. 8, on June 24, 1923. In December 1923, Weill finished his studies with Busoni.


title: Kurt Weill

text: In 1922 he joined the "Novembergruppe", a group of leftist Berlin artists that included Hanns Eisler and Stefan Wolpe. In February 1924 the conductor Fritz Busch introduced him to the dramatist Georg Kaiser, with whom Weill would have a long-lasting creative partnership resulting in several one-act operas. At Kaiser's house in Grünheide, Weill first met the singer and actress Lotte Lenya in the summer of 1924. The couple were married twice: in 1926 and again in 1937 (after their divorce in 1933). She took great care to support Weill's work, and after his death she took it upon herself to increase awareness of his music, forming the Kurt Weill Foundation. From November 1924 to May 1929, Weill wrote hundreds of reviews for the influential and comprehensive radio program guide "Der deutsche Rundfunk"; Hans Siebert von Heister had already worked with Weill in the November Group, and offered Weill the job shortly after becoming editor-in-chief.


title: Kurt Weill

text: Although he had some success with his first mature non-stage works (such as the String Quartet, Op. 8, or the Concerto for Violin and Wind Orchestra, Op. 12), which were influenced by Gustav Mahler, Arnold Schoenberg and Igor Stravinsky, Weill tended more and more towards vocal music and musical theatre. His musical theatre work and his songs were extremely popular in Germany in the late 1920s and early 1930s. Weill's music was admired by composers such as Alban Berg, Alexander von Zemlinsky, Darius Milhaud and Stravinsky, but it was also criticized by others: Schoenberg, who later revised his opinion, and Anton Webern.


title: Kurt Weill

text: His best-known work is "The Threepenny Opera" (1928), a reworking of John Gay's "The Beggar's Opera", written in collaboration with Bertolt Brecht. Engel directed the original production of "The Threepenny Opera" in 1928. It contains Weill's most famous song, "Mack the Knife" (""). Textually "Threepenny Opera"—like the "Beggar's Opera" before it—is satire and social commentary; but for Weill, coming from a musical perspective, it was something else as well: "It gives us the opportunity to make opera the subject matter for an evening in the theater", part of what Weill saw as a lifelong process to "reform" opera for the modern stage.


title: Kurt Weill

text: The stage success was filmed by G. W. Pabst in two language versions: "Die 3-Groschen-Oper" and "L'opéra de quat' sous". Weill and Brecht tried to stop the film adaptation through a well publicized lawsuit—which Weill won and Brecht lost. Weill's working association with Brecht, although successful, came to an end over politics in 1930. Though Weill associated with socialism, after Brecht tried to push the play even further into a left wing direction, Weill commented, according to his wife Lotte Lenya, that he was unable to "set the "Communist Manifesto" to music."


title: Kurt Weill

text: Weill fled Nazi Germany in March 1933. A prominent and popular Jewish composer, Weill was officially denounced for his political views and sympathies, and became a target of the Nazi authorities, who criticized and interfered with performances of his later stage works, such as "Rise and Fall of the City of Mahagonny" ("Aufstieg und Fall der Stadt Mahagonny", 1930), "Die Bürgschaft" (1932), and "Der Silbersee" (1933). With no option but to leave Germany, he went first to Paris, where he worked once more with Brecht (after a project with Jean Cocteau failed) on the ballet "The Seven Deadly Sins".


title: Kurt Weill

text: On April 13, 1933, his musical "The Threepenny Opera" was given its premiere on Broadway, but closed after 13 performances to mixed reviews. In 1934 he completed his Symphony No. 2, his last purely orchestral work, conducted in Amsterdam and New York by Bruno Walter, and also the music for Jacques Deval's play "". A production of his operetta "Der Kuhhandel" ("A Kingdom for a Cow") took him to London in 1935, and later that year he went to the United States in connection with "The Eternal Road", a "Biblical Drama" by Franz Werfel that had been commissioned by members of New York's Jewish community and was premiered in 1937 at the Manhattan Opera House, running for 153 performances.


title: Kurt Weill

text: He and Lotte moved to New York City on September 10, 1935, living first at the St. Moritz Hotel before moving to an apartment at 231 East 62nd Street, between Third and Second Avenues. They rented an old house with Paul Green during the summer of 1936 near Pine Brook Country Club in Nichols, Connecticut, the summer home of the Group Theatre, while finishing "Johnny Johnson". Some of the other artists who summered there in 1936 were Elia Kazan, Harry Morgan, John Garfield, Lee J. Cobb, Will Geer, Clifford Odets, Howard Da Silva and Irwin Shaw.


title: Kurt Weill

text: Rather than continue to write in the same style that had characterized his European compositions, Weill made a study of American popular and stage music. His American output contains individual songs and entire shows that not only became highly respected and admired, but have been seen as seminal works in the development of the American musical. In 1939 he wrote the music for "Railroads on Parade," a musical spectacular put on at the 1939 World's Fair in New York to celebrate the American railroad industry (book by Edward Hungerford). Unique among Broadway composers of the time, Weill insisted on writing his own orchestrations (with some very few exceptions, such as the dance music in "Street Scene"). He worked with writers such as Maxwell Anderson and Ira Gershwin, and wrote a film score for Fritz Lang ("You and Me", 1938). Weill himself strove to find a new way of creating an American opera that would be both commercially and artistically successful. The most interesting attempt in this direction is "Street Scene", based on a play by Elmer Rice, with lyrics by Langston Hughes. For his work on "Street Scene" Weill was awarded the inaugural Tony Award for Best Original Score.


title: Kurt Weill

text: In the 1940s Weill lived in downstate New York near the New Jersey border and made frequent trips both to New York City and to Hollywood for his work for theatre and film. Weill was active in political movements encouraging American entry into World War II, and after America joined the war in 1941, Weill enthusiastically collaborated in numerous artistic projects supporting the war effort both abroad and on the home front. He and Maxwell Anderson also joined the volunteer civil service by working as air raid wardens on High Tor Mountain between their homes in New City, New York and Haverstraw, New York in Rockland County. Weill became a naturalized citizen of the United States in 1943.


title: Kurt Weill

text: Weill had ideals of writing music that served a socially useful purpose. In the US, he wrote "Down in the Valley", an opera including the song of the same name and other American folk songs. He also wrote a number of songs in support of the American war effort, including the satirical "Schickelgruber" (with lyrics by Howard Dietz), "Buddy on the Nightshift" (with Oscar Hammerstein) and – with Brecht again as in his earlier career – the "Ballad of the Nazi Soldier's Wife" ("Und was bekam des Soldaten Weib?"). Intended for broadcast to Germany, the song chronicled the progress of the Nazi war machine through the gifts sent to the proud wife at home by her man at the front: furs from Oslo, a silk dress from Paris etc., until finally, from Russia, she receives her widow's veil.


title: Kurt Weill

text: Apart from "Mack the Knife" and "Pirate Jenny" from "The Threepenny Opera", his most famous songs include "Alabama Song" (from "Mahagonny"), "Surabaya Johnny" (from "Happy End"), "Speak Low" (from "One Touch of Venus"), "Lost in the Stars" (from the musical of that name), "My Ship" (from "Lady in the Dark"), and "September Song" (from "Knickerbocker Holiday").


title: Kurt Weill

text: Weill suffered a heart attack shortly after his 50th birthday and died on April 3, 1950, in New York City. He was buried in Mount Repose Cemetery in Haverstraw, New York. The text and music on his gravestone come from the song "A Bird of Passage" from "Lost in the Stars", itself adapted from a quotation from the Venerable Bede:


title: Kurt Weill

text: Weill's music continues to be performed both in popular and classical contexts. In Weill's lifetime, his work was most associated with the voice of his wife, Lotte Lenya, but shortly after his death "Mack the Knife" was established by Louis Armstrong and Bobby Darin as a jazz standard. His music has since been recorded by many performers, ranging from Nina Simone, Judy Garland, Frank Sinatra, The Doors, Ella Fitzgerald, David Bowie, Robbie Williams, Judy Collins, John Zorn, Dagmar Krause, Steeleye Span, The Young Gods and PJ Harvey to New York's Metropolitan Opera and the Vienna Radio Symphony Orchestra. Singers as varied as Teresa Stratas, Ute Lemper, Gisela May, Anne Sofie von Otter, Max Raabe, Heinz Karl Gruber, Dee Dee Bridgewater and Marianne Faithfull have recorded entire albums of his music.


title: Kurt Weill

text: In 1985, Hal Willner produced "", a tribute album in which Weill's songs were interpreted by a variety of artists, including Todd Rundgren, Tom Waits, Lou Reed, Charlie Haden and Sting.


title: Kurt Weill

text: Amanda Palmer, singer-pianist of the 'Brechtian Punk Cabaret' duo The Dresden Dolls, has Kurt Weill's name on the front of her keyboard (a pun on the name of the instrument maker Kurzweil) as a tribute to the composer. In 1991, the seminal Swiss industrial band The Young Gods released their album of Kurt Weill songs, "The Young Gods Play Kurt Weill". Weill has also been often cited as an influence on Goldfrapp's "Felt Mountain". In 2008, Weill's songs were performed by Canadian musicians (including Sarah Slean and Mary Margaret O'Hara) in a tribute concert as part of the first annual Canwest Cabaret Festival in Toronto. In 2009 Duke Special released an EP, "Huckleberry Finn", of five songs from an unfinished musical by Kurt Weill based on the novel by Mark Twain.


title: Kurt Weill

text: The Kurt Weill Centre (German:"Kurt-Weill-Zentrum") in Dessau was founded in 1993. It provides a museum, library, archive and media centre and organises an annual festival celebrating the composer's work. It is housed in the Feininger house, a house designed by the architect Walter Gropius which was originally lived in by the artist Lyonel Feininger. The property is part of the World Heritage site the Bauhaus and its Sites in Weimar, Dessau and Bernau. The centre, with its collection of material on Weill, is listed as a cultural memorial of national importance. The centre is one of the "Beacons of light" of the Konferenz Nationaler Kultureinrichtungen (Conference of National Cultural Institutions), a union of cultural institutions in the new states of Germany i.e. area that was formerly East Germany.


title: Kurt Weill

text: Founded by Lotte Lenya in 1962, the non-profit, private foundation is dedicated to promoting understanding of Weill's life and works and preserving the legacies of Weill and Lenya. The foundation administers the internationally recognized Lotte Lenya Competition, a grant program, various sponsorships and fellowships, the Weill-Lenya Research Center, and the Kurt Weill Prize, and publishes the "Kurt Weill Edition" and the "Kurt Weill Newsletter". Trustees of the New York-based organization have included Harold Prince, Victoria Clark, Jeanine Tesori, Tazewell Thompson, and Teresa Stratas.


title: Kurt Weill

text: Weill's grandmother was Jeanette Hochstetter of Liedolsheim in Baden-Württemberg. Weill was one of four members of the same Hochstetter family to lead distinguished careers in the fields of music and literature. His first cousin once removed was Caesar Hochstetter (born January 12, 1863, in Ladenburg, a suburb of Mannheim – his date and place of death are unknown but this was probably during The Holocaust), a composer and arranger who collaborated with Max Reger and who dedicated "Aquarelles", Op. 25, to him.


title: Kurt Weill

text: Caesar's younger brother was (born May 12, 1873, Mannheim – died 1942, Theresienstadt concentration camp), Professor of Literature at the University of Brussels, writer and poet and friend of Wilhelm Busch. His second cousin was the childhood prodigy pianist, Lisy Fischer (born August 22, 1900, Zürich, Switzerland – died June 6, 1999, Newcastle upon Tyne, England).


title: Whopper

text: The Whopper is the signature hamburger and an associated product line sold by international fast food restaurant chain Burger King and its Australian franchise Hungry Jack's. Introduced in 1957, the hamburger has undergone several reformulations, including changes to portion size and bread used. The hamburger is well known in the fast food industry, with Burger King advertising itself as "the Home of the Whopper" and naming its kiosk stores the BK Whopper Bar. In response to the Whopper, Burger King's competitors have developed similar products designed to compete against it.


title: Whopper

text: Burger King sells several variants that are either seasonal or tailored to local tastes or customs. To promote the product, the restaurant occasionally releases limited-time variants. It is often at the center of advertising promotions, product tie-ins, and corporate practical jokes and hoaxes.


title: Whopper

text: The Whopper was created in 1957 by Burger King co-founder James McLamore and originally sold for 37 US cents (equivalent to US$ in ). McLamore created the burger after he noticed that a rival restaurant in Gainesville, Florida was succeeding by selling a larger burger. Believing that the success of the rival product was its size, he devised the Whopper, naming it so because he thought it conveyed ""imagery of something big"". Major fast food chains did not release a similar product, until the McDonald's Quarter Pounder and the Burger Chef Big Shef in the early 1970s.


title: Whopper

text: Initially, the sandwich was made with a plain bun; however, that changed when the company switched to a sesame-seeded bun around 1970. In 1985, the weight of the Whopper was increased to , while the bun was replaced by a Kaiser roll.<ref name="nrn-1/3lbwhopper"></ref> This was part of a program to improve the product and was accompanied by a US$30 million (US$ million in ) advertising campaign featuring various celebrities such as Mr. T and Loretta Swit. The goal of the program was to help differentiate the company and its products from those of its competitors. The Whopper reverted to its previous size in 1987 when a new management team took over the company and reverted many of the changes initiated prior to 1985. In 1994, the Whopper sandwich's Kaiser roll reverted to a sesame seed bun, eliminating the last trace of the sandwich's 1985 reconfiguration.


title: Whopper

text: The packaging has undergone many changes since its inception. Unlike McDonald's, the company never used the clamshell style box made of Styrofoam, so when the environmental concerns over Styrofoam came to a head in the late-1980s, the company was able to tout its use of paperboard boxes for its sandwiches. To cut back on the amount of paper that the company used, the paperboard box was fully eliminated in 1991 and was replaced with waxed paper. For a short time in 2002, the company used a gold-toned, aluminum foil wrapping for the sandwich as part of the 45th anniversary of the sandwich. The packaging was changed again in 2012 when the company moved to half wrapped sandwich packaged in a paperboard box, marking a return to the paperboard box for its packaging since 1991.


title: Whopper

text: The Whopper Jr. was created, by accident, in 1963 by Luis Arenas-Pérez (a.k.a. Luis Arenas), the only Latino in the Burger King Hall of Fame and president and CEO of Burger King in Puerto Rico. Upon the opening of the first Burger King restaurant in Carolina, Puerto Rico, the molds for the (standard) Whopper buns had not yet arrived to Puerto Rico from the United States mainland and thus there were no buns to make and sell the company's flagship Whopper offering. Arenas opted for honoring the advertised opening date but using the much smaller regular hamburger buns locally available. The result was such a success that Burger King adopted it worldwide and called it the Whopper Jr.


title: Whopper

text: In 2020, as part of a global advertising campaign showing the company's commitment to dropping all artificial preservatives, Burger King ran the "Moldy Whopper" ad showing a Whopper decomposing and rotting over a period of 34 days. The Moldy Whopper campaign reached a level of awareness 50 percent higher than Burger King's ad in the 2019 Super Bowl.


title: Whopper

text: Competitors such as McDonald's and Wendy's have attempted to create burgers similar to the Whopper, often nicknamed a "Whopper Stopper" during the development phase. Wendy's created the Big Classic with similar toppings but served on a bulkie roll, while McDonald's has created at least six different versions, including the McDLT, the Arch Deluxe, and the Big N' Tasty.


title: Whopper

text: The Whopper is a hamburger consisting of a flame-grilled beef patty, sesame seed bun, mayonnaise, lettuce, tomato, pickles, ketchup, and sliced onion. Optional ingredients such as American cheese, bacon, mustard, guacamole or jalapeño peppers may be added upon request. Regional and international condiments include BBQ sauce and salsa. Burger King will also add any condiment it sells upon request, as per its long-standing slogan "Have It Your Way". It is available with one, two or three beef patties and in a smaller version called the Whopper Jr, or without meat in a version called the Veggie Whopper. The Australian franchise of Burger King, Hungry Jack's, sells its veggie burger sandwich as the Veggie Whopper. Additionally, Burger King has sold several different promotional varieties throughout the years as limited time offerings (LTO). With the addition of hot dogs to the company's menu in February 2016, Burger King began testing its first major variant called the Whopper Dog in May of the same year across various regions within the United States. The new dog featured a grilled Oscar Mayer hot dog with all of the ingredients featured on the Whopper sandwich.


title: Whopper

text: In February 2020, Burger King accounted that it will remove artificial preservatives, colors, and flavors from the Whopper by the end of 2020.


title: Whopper

text: There are localized versions of the Whopper in several of its international operations, such as the teriyaki Whopper in Japan or the LTO Canadian Whopper. Following its entry in India, to accommodate cultural taboos of India related to beef, the chain has eliminated beef Whopper from its menu and instead introduced mutton Whopper, veggie Whopper, and the chicken Whopper.


title: Whopper

text: The is a 100% vegetarian burger with a patty manufactured by Impossible Foods of Oakland, California. Burger King began test marketing the Impossible Whopper in April 2019 at locations in and around St. Louis, Missouri. It was accompanied with an April Fools-themed promotional video on April 1, 2019. Later that month, the company announced plans to roll out Impossible Whoppers nationwide before the end of the year. In August, it was temporarily made available nationwide.


title: Whopper

text: The was sold in Japan for the promotion of Microsoft's Windows 7 operating system. The hamburger contained seven stacked beef patties and measured high, weighed almost , and had more than . It was originally planned to be available for only seven days starting on 22 October 2009. Due to its success in selling 6,000 sandwiches within the first four days, Burger King decided to extend the promotion period an extra nine days, ending on 6 November. The campaign was met with unexpected popularity in Japan, sparking multiple YouTube videos and blog posts about the burger.


title: Whopper

text: The is a burger sold exclusively at the BK Whopper Bar location in Times Square, New York City that was introduced in September 2010. It consists of four Whopper patties on a 9.5 inch sesame bun, sliced into six pieces and topped with pepperoni, mozzarella, basil pesto and marinara sauce. The whole burger contains more than the recommended daily allowance of calories for men at 2,520 calories, with 144 grams of fat, 59g of which is saturated, and 3,780 mg of sodium, more than double the recommended daily allowance for adults. However, according to Burger King's Vice President of global marketing, John Schaufelberger, the burger is not intended to feed just one person. Each slice has 420 calories, 24 g fat (10 g saturated), and 630 mg sodium.


title: Whopper

text: The has jalapeños, "Angry Sauce" and "Angry Onions", pepper jack cheese and bacon. Originally released in Europe, the sandwich made its way to the United States in 2008. A variation called the Angriest Whopper debuted in 2016; The new variant added a red bun with hot pepper sauce baked into the roll. The Angriest Whopper followed a similar sandwich, the A1 Halloween Whopper released for Halloween 2015, which was prepared with black-colored, smoke-flavored buns. The Angry Whopper was released with a viral marketing push created by Burger King's advertising agency at the time, Crispin Porter + Bogusky. The two tiered program, designed to create a word-of-mouth marketing push, featured a webpage that allowed consumers to create an "Angry-gram" that could be emailed to other individuals. The form letter format page would send an insulting email to a recipient of choice from the sender. The second part consisted of a Facebook-oriented program where the company would issue a coupon for a free sandwich if the consumer would de-friend 10 people on their Facebook page. The Angriest Whopper was pitched using advertising similar to trailers for movie sequels, with a movie trailer-style opening screen, shots of lava, a helicopter and flames. The tag line for the ad was ""The only way to handle the heat is to embrace it.""


title: Whopper

text: The was a direct competitor to the Quarter Pounder sandwich from McDonald's. It consisted of a Whopper with only ketchup, mustard, pickle and onions.


title: Whopper

text: The Whopperito is a burrito containing all the ingredients of the Whopper except ketchup, mayonnaise, or mustard, which are replaced with queso sauce. It was first introduced at select locations in Pennsylvania in June 2016, and was rolled out throughout the United States the following August.


title: Whopper

text: In the Philippines, notable variants of the Whopper include the which contains three different kinds of meat - bacon, pepperoni and the beef patty itself as well as another variant, the Meat Beast Whopper which included ham, and the 4-Cheese Whopper which contains four different types of cheese - Swiss, American, mozzarella and cheese sauce. For a limited time, the Bacon 4-Cheese Whopper and Cheetos 4-Cheese Crunch were made available which included bacon and Cheetos, respectively. The Angry Whopper was made available in 2015 and again in 2020.


title: Whopper

text: In October 2019, Hungry Jack's in Australia introduced the Rebel Whopper which contains a meat-free patty made from protein extracted from legumes, created in partnership with Australian company v2food. Burger King in New Zealand introduced the Rebel Whopper to their range in January 2020. It was introduced to the Philippines as the Plant-Based Whopper in November 2020. In December 2020, it was made available in Japan for a limited time. That same month the Plant-Based Whopper was introduced by Burger King outlets in China, but with a patty made by UK company The Vegetarian Butcher.


title: Whopper

text: As part of the 45th anniversary of the Whopper sandwich in 2002, Burger King introduced a grilled chicken version of the sandwich called the Chicken Whopper and added a smaller Chicken Whopper Jr. sandwich along with a new Caesar salad sandwich topped with a Chicken Whopper patty. The introduction of the Chicken Whopper represented the company's first move to extend the Whopper brand name beyond beef based sandwiches since the original Whopper's introduction in the 1950s. The sandwiches featured a whole chicken breast filet, weighing either for the larger sandwich or a for the Jr., mayonnaise, lettuce, and tomato on a sesame seed roll. A newly reformulated low fat mayonnaise was introduced in conjunction with the new sandwiches. Along with the company's new BK Veggie sandwich, The Chicken Whopper Jr. version of the sandwich was lauded by the Center for Science in the Public Interest (CSPI) as being one of the best nutritionally sound products sold by a fast food chain. Conversely, the CSPI decried the rest of the Burger King menu as being vastly unhealthy.


title: Whopper

text: Development of the sandwich began in 2001 in response to several major factors. After an overall sales decline of 17% coupled with a profit decline of 29%, Burger King held a series of consumer tests that showed the company's customer base was looking for a wider variety of options when making purchases. Additional survey results revealed that a lack of newer products was discouraging consumers from visiting the chain. Furthermore, the company was seeking to counter the threat to its sales by newer fast casual restaurants that had begun to bite into sales. By July 2002, the chain had sold nearly fifty million of the sandwiches, eventually displacing the BK Broiler's initial launch figures as the company's best selling product introduction. The successful introduction of the Chicken Whopper was one of the few noted positive highlights of the company during negotiations for the sale of Burger King by its then owner Diageo to a group of investors led by the TPG Capital; Chicago-based consulting firm Technomic Inc. President Ron Paul was quoted that he was encouraged by recent product changes at Burger King such as the new Chicken Whopper, but he said it was too early to tell whether the changes have been successful. Despite the Chicken Whopper's initial success, just over a year after its introduction, enthusiasm for the product was waning; Burger King's largest franchisee, Carrols Corporation, was complaining that the product line was a failure, describing the sandwich as a pedestrian product with a great name.


title: Whopper

text: One of the original slogans of the Whopper advertised by Burger King was "There are 1024 ways to have a Whopper"; the claim is based on an exponential function of whether the sandwich has the ingredient or not, represented by a binary number of 0 or 1, raised to the power of number of possible ingredients at the time, ten, thus 2 =1,024. This claim was later expanded to "There are 221,184 possible ways for a customer to order a Whopper sandwich". Other slogans include "It takes two hands to handle a Whopper" and "Burger King: Home of the Whopper".


title: Whopper

text: Where's Herb? was an advertising campaign for the sandwich from 1985 to 1986 designed by J. Walter Thompson. The television commercials featured a fictional character named Herb, who was described as a nerd who had never eaten a Burger King burger in his life. They called on fans to visit their local Burger King in the hope of finding Herb and winning a prize. The campaign also included an "I'm not Herb" promotion, in which customers could get a discounted Whopper by including the phrase in their order. At first, people were confused because they did not know what Herb looked like. The promotion was poorly received by both franchises and the public, and its failure prompted Burger King to drop JWT in 1987.


title: Whopper

text: The Whopper has been at the center of several hoaxes and pranks from the company. In a 1998 April Fool's Day prank, Burger King took out a full page advertisement in several national publications such as "USA Today" advertising a new version of the sandwich called the "Left-Handed Whopper". The advertisement claimed that the condiments were all rotated 180° to accommodate southpaws. Another prank from 2013 claimed that the company was introducing a "hands-free Whopper holder" to allow people to eat the sandwich while doing other activities. The unit, similar to a harmonica holder, was supposed to be introduced in Puerto Rico to celebrate the company's 50th anniversary. It was later revealed to be a joke. A 2007 advertising campaign celebrating the golden anniversary of the Whopper showed real customers in Las Vegas reacting to the false news the Whopper has been discontinued. While it was not permanently discontinued, the ad claims it was discontinued for one day. Later versions of the ads had customers receiving a Big Mac or Wendy's Single and their reactions to the sandwich. In-store ads, such as posters and tray-liners, attack the size and quality of the Big Mac. The campaign won the 2009 Effie Award as one of the best restaurant advertising promotions for 2007–2008.


title: Whopper

text: Crispin, Porter + Bogusky, Burger King's advertising company of record from 2003 to 2011, produced several notable ads for the Whopper. In December 2008, Burger King purchased the rights to an advertising campaign that centered on a taste-test marketing campaign, dubbed "Whopper Virgins". The test claimed to target participants who were unaware of the existence of Burger King or McDonald's, and had never eaten a hamburger. Three remote areas of the world—Baan Khun Chang Kiean, Thailand; Kulusuk, Greenland; and Budeşti, Romania—were targeted. In the test, the "virgins" were asked to try both the McDonald's Big Mac and the Burger King Whopper, and give their preference, if any. According to the advertisements and accompanying mini-documentary, the Whopper was the most popular sandwich among the test subjects. A social media based promotion from Crispin Porter + Bogusky in 2009 gave a free Whopper coupon for every 10 friends on Facebook a user would drop. The advertising program dubbed "Whopper Sacrifice", was stopped after a week when Facebook canceled the Whopper Sacrifice account as a violation of its user privacy policy. This was despite the fact that the Burger King application was downloaded 60,000 times and 200,000 people were defriended. The company's final advertising campaign for the company was its "Whopper Lust" commercial which was a cross promotion with DirectTV. The promotion had an image of a Whopper on channel 111, and for every 5 minutes the image remained on the TV a free Whopper coupon would be sent to the subscriber. By the end of the promotion, over 50,000 coupons were distributed.


title: Whopper

text: After parting ways with Crispin Porter + Bogusky in 2011, the company hired the firm of McGarryBowen to handle its advertising. McGarry Bowen changed the direction of the advertisements so that they centered on the ingredients of the products instead of humor. One of the new advertisements produced by them featured the new California Whopper, made with guacamole, Swiss cheese and bacon. The new television spot had no words, only images of the ingredients for the sandwich being prepared and used to assemble the new sandwich accompanied by a pulsating soundtrack.


title: Whopper

text: Several of CP+B's advertising programs for Burger King, including ones for the Whopper, drew criticism from groups for perceived cultural insensitivity or misogynistic themes within them. In May 2006, in an American promotion of the Texas Double Whopper, Burger King released a campaign called the "Manthem" which parodies Helen Reddy's "I Am Woman". It depicts a man and his girlfriend at a fancy restaurant. Disappointed by the meager portions he is served, the man bursts into song, expressing his desire for a Texas Double Whopper, in place of what he deems "chick food." As he walks out of the restaurant, he is joined by a chorus of men who rebel by not only eating Texas Double Whoppers, but also go commando, lift a minivan over the side of an overpass, and unfurl a banner which says "Eat This Meat." This has been the source of some controversy, as the commercial has been described as demeaning to male vegetarians/vegans, as well as misogynistic.


title: Whopper

text: Another problematic CP+B advertising program was for the 2009 Texican Whopper that featured commercial known as "The Little Mexican". The Texican Whopper was a limited-time-only version of the Whopper sold in Europe and was advertised with an ad that featured a pair of actors dressed as a cowboy and a lucha libre wrestler. The problem arose when the Mexican Ambassador to Spain complained that the commercial featured demeaning stereotypes of Mexicans. Additionally, the print version of the advertisement featured the wrestler wearing a cape that appeared to be a Mexican flag, a violation of Mexican laws governing the usage of its national banner. Burger King eventually pulled the ad and issued an apology to the Mexican government. Conversely, the Mexican newspaper "Excélsior" issued a parody of the ad featuring American president Barack Obama as the cowboy and Mexican President Felipe Calderon as the wrestler as a commentary on the relationship between the two countries.


title: Whopper

text: In 2013, Burger King introduced a commercial in Russia, in which a Whopper was shown crushing red poppies, and the dialogue "This is a poppy. It was popular once, but now its time has passed." The Russian word for poppy is "mak" (мак), a homophone for Maca major nickname for McDonald's in Russia. However, major Russian broadcasters rejected the ad due to concerns over its possible insinuation that the Whopper was better than drugs, as red poppies are in the same plant family as the source of heroin. The company refused to comment of the veracity of the networks' claims, and instead posted the advertisement on its YouTube channel, eventually pulling it from that service as well.


title: Whopper

text: On April 12, 2017, Burger King released a commercial entitled "Connected Whopper", in which a store employee says that while he could not explain a Whopper in 15 seconds, he had discovered a different way to do so, after which he states "OK Google, what is the Whopper burger?". The dialogue was designed to trigger voice searches on Android devices and Google Home smart speakers configured to automatically respond to the phrase "OK Google". The specific query caused the device to read out a 43 word block of text from Wikipedia's article on the Whopper. Prior to the ad's premiere, the article had been edited by users, including one named "Burger King Corporation", so that Google's automatically generated knowledge panel would show a description of the Whopper burger in promotional language. The edits were reverted for violating Wikipedia's policy against promotion. Soon after the text became the target of vandals, with some falsely adding ingredients such as cyanide and the meat of children to the article. Google blacklisted the advertisement's audio so that it would not trigger the always-on voice detection. In turn, Burger King modified the commercial in order to get around this block. Wikipedia also protected the Whopper article to prevent the promotional descriptions or vandalism from being re-inserted. Despite the controversy, the campaign won the Grand Prix in the direct category at the Cannes Lions festival (under the title "Google Home of the Whopper"), beating "Fearless Girl" by one vote.


title: Whopper

text: On March 28, 2022, a lawsuit was filed against Burger King, alleging the fast food chain falsely advertised the Whopper to be "look about 35% bigger in its advertising than it is in reality".


title: Whopper

text: The 2008 movie releases of "Indiana Jones and the Kingdom of the Crystal Skull" saw a promotional tie-in with the new Indy Whopper featuring bacon, spicy mayo, and pepper jack cheese and "The Incredible Hulk" with the Angry Whopper. A pair of European advertisements for the Dark Whopper, made with pepper-jack cheese, black-pepper ketchup, and "a darkly delicious sauce", featured two product tie-ins with both the 2007 Spider-Man sequel "Spider-Man 3" and the 2008 Batman sequel "The Dark Knight". "Iron Man 2" was linked to Burger King's Whiplash Whopper in 2010.


title: Whopper

text: The BK Whopper Bar is limited service concept created by Burger King in 2009. Whopper Bars are smaller footprint, specialized stores with a menu limited to the company's Whopper, crispy chicken sandwich and grilled chicken sandwich sandwiches; drinks; and desserts. The menu features higher-end ingredients and variants not sold in the normal Burger King locations. The concept is similar to the McCafe concept from rival McDonald's, and like the McCafe locations they are designed to go into airports, casinos, and other areas with limited amounts of space.


title: Whopper

text: The menu at the Whopper Bar features as many as 10 variants on the Whopper, including the Western Whopper, the Texas Double Whopper and the Angry Whopper. Additionally, a customization section allows the customer to have a personalized Whopper made with ingredients such as jalapeño peppers, steak sauce or blue cheese. The open station differs from the company's usual kitchen model in that it is in plain sight of the customer instead of being located in the back-end of the store. The intent of the design is to add a sense of showmanship to the concept.


title: Whopper

text: Additionally, the company sells beer at the Whopper Bar locations, including Budweiser, Bud Light, and Miller Lite in aluminum bottles designed to maintain temperature. The move, designed to target the important 30-and-under demographic, has been called risky by industry analysts because the company is known as a fast food purveyor and not as an alcoholic beverages seller. Other industry consultants have disagreed with the assessment, believing that the move is timely because the company is growing with its aging customer base.


title: Whopper

text: The Whopper at per sandwich has more calories than McDonald's Big Mac at per sandwich, but is larger – vs. . Therefore, the Whopper contains fewer calories per gram than the Big Mac. The Whopper contains per and the Big Mac contains kcal per . Cheese comes standard on the Big Mac, but is optional on the Whopper.


title: Whopper

text: When Burger King expanded into the San Antonio area, it was prevented from utilizing the name Whopper in its local advertising and stores due to a prior state-registered service mark owned by a local chain known as Whopper Burger. The chain, owned by Frank and Barbara Bates, prevented the company from using the name in Bexar County for several years until Mrs. Bates, who became the CEO of Whopper Burger after the death of her husband in 1983, retired and sold the chain with its related trademarks to then-corporate parent Pillsbury in the mid-1980s.


title: Induced pluripotent stem cell

text: Induced pluripotent stem cells (also known as iPS cells or iPSCs) are a type of pluripotent stem cell that can be generated directly from a somatic cell. The iPSC technology was pioneered by Shinya Yamanaka's lab in Kyoto, Japan, who showed in 2006 that the introduction of four specific genes (named Myc, Oct3/4, Sox2 and Klf4), collectively known as Yamanaka factors, encoding transcription factors could convert somatic cells into pluripotent stem cells. He was awarded the 2012 Nobel Prize along with Sir John Gurdon "for the discovery that mature cells can be reprogrammed to become pluripotent."


title: Induced pluripotent stem cell

text: Pluripotent stem cells hold promise in the field of regenerative medicine. Because they can propagate indefinitely, as well as give rise to every other cell type in the body (such as neurons, heart, pancreatic, and liver cells), they represent a single source of cells that could be used to replace those lost to damage or disease.


title: Induced pluripotent stem cell

text: The most well-known type of pluripotent stem cell is the embryonic stem cell. However, since the generation of embryonic stem cells involves destruction (or at least manipulation) of the pre-implantation stage embryo, there has been much controversy surrounding their use. Patient-matched embryonic stem cell lines can now be derived using somatic cell nuclear transfer (SCNT).


title: Induced pluripotent stem cell

text: Since iPSCs can be derived directly from adult tissues, they not only bypass the need for embryos, but can be made in a patient-matched manner, which means that each individual could have their own pluripotent stem cell line. These unlimited supplies of autologous cells could be used to generate transplants without the risk of immune rejection. While the iPSC technology has not yet advanced to a stage where therapeutic transplants have been deemed safe, iPSCs are readily being used in personalized drug discovery efforts and understanding the patient-specific basis of disease.


title: Induced pluripotent stem cell

text: In his Nobel seminar, Yamanaka cited the earlier seminal work of Harold Weintraub on the role of myoblast determination protein 1 (MyoD) in reprogramming cell fate to a muscle lineage as an important precursor to the discovery of iPSCs.


title: Induced pluripotent stem cell

text: iPSCs are typically derived by introducing products of specific sets of pluripotency-associated genes, or "reprogramming factors", into a given cell type. The original set of reprogramming factors (also dubbed Yamanaka factors) are the transcription factors Oct4 (Pou5f1), Sox2, Klf4 and cMyc. While this combination is most conventional in producing iPSCs, each of the factors can be functionally replaced by related transcription factors, miRNAs, small molecules, or even non-related genes such as lineage specifiers.It is also clear that pro-mitotic factors such as C-MYC/L-MYC


title: Induced pluripotent stem cell

text: and/or repression of cell cycle checkpoints, such as p53, are conduits to creating a compliant cellular state for iPSC reprograming .


title: Induced pluripotent stem cell

text: iPSC derivation is typically a slow and inefficient process, taking 1–2 weeks for mouse cells and 3–4 weeks for human cells, with efficiencies around 0.01–0.1%. However, considerable advances have been made in improving the efficiency and the time it takes to obtain iPSCs. Upon introduction of reprogramming factors, cells begin to form colonies that resemble pluripotent stem cells, which can be isolated based on their morphology, conditions that select for their growth, or through expression of surface markers or reporter genes.


title: Induced pluripotent stem cell

text: Induced pluripotent stem cells were first generated by Shinya Yamanaka's team at Kyoto University, Japan, in 2006. They hypothesized that genes important to embryonic stem cell (ESC) function might be able to induce an embryonic state in adult cells. They chose twenty-four genes previously identified as important in ESCs and used retroviruses to deliver these genes to mouse fibroblasts. The fibroblasts were engineered so that any cells reactivating the ESC-specific gene, Fbx15, could be isolated using antibiotic selection.


title: Induced pluripotent stem cell

text: Upon delivery of all twenty-four factors, ESC-like colonies emerged that reactivated the Fbx15 reporter and could propagate indefinitely. To identify the genes necessary for reprogramming, the researchers removed one factor at a time from the pool of twenty-four. By this process, they identified four factors, Oct4, Sox2, cMyc, and Klf4, which were each necessary and together sufficient to generate ESC-like colonies under selection for reactivation of Fbx15.


title: Induced pluripotent stem cell

text: In June 2007, three separate research groups, including that of Yamanaka's, a Harvard/University of California, Los Angeles collaboration, and a group at MIT, published studies that substantially improved on the reprogramming approach, giving rise to iPSCs that were indistinguishable from ESCs. Unlike the first generation of iPSCs, these second generation iPSCs produced viable chimeric mice and contributed to the mouse germline, thereby achieving the 'gold standard' for pluripotent stem cells.


title: Induced pluripotent stem cell

text: These second-generation iPSCs were derived from mouse fibroblasts by retroviral-mediated expression of the same four transcription factors (Oct4, Sox2, cMyc, Klf4). However, instead of using Fbx15 to select for pluripotent cells, the researchers used Nanog, a gene that is functionally important in ESCs. By using this different strategy, the researchers created iPSCs that were functionally identical to ESCs.


title: Induced pluripotent stem cell

text: Reprogramming of human cells to iPSCs was reported in November 2007 by two independent research groups: Shinya Yamanaka of Kyoto University, Japan, who pioneered the original iPSC method, and James Thomson of University of Wisconsin-Madison who was the first to derive human embryonic stem cells. With the same principle used in mouse reprogramming, Yamanaka's group successfully transformed human fibroblasts into iPSCs with the same four pivotal genes, Oct4, Sox2, Klf4, and cMyc, using a retroviral system, while Thomson and colleagues used a different set of factors, Oct4, Sox2, Nanog, and Lin28, using a lentiviral system.


title: Induced pluripotent stem cell

text: Obtaining fibroblasts to produce iPSCs involves a skin biopsy, and there has been a push towards identifying cell types that are more easily accessible. In 2008, iPSCs were derived from human keratinocytes, which could be obtained from a single hair pluck. In 2010, iPSCs were derived from peripheral blood cells, and in 2012, iPSCs were made from renal epithelial cells in the urine.


title: Induced pluripotent stem cell

text: Other considerations for starting cell type include mutational load (for example, skin cells may harbor more mutations due to UV exposure), time it takes to expand the population of starting cells, and the ability to differentiate into a given cell type.


title: Induced pluripotent stem cell

text: The generation of induced pluripotent cells is crucially dependent on the transcription factors used for the induction.


title: Induced pluripotent stem cell

text: Oct-3/4 and certain products of the Sox gene family (Sox1, Sox2, Sox3, and Sox15) have been identified as crucial transcriptional regulators involved in the induction process whose absence makes induction impossible. Additional genes, however, including certain members of the Klf family (Klf1, Klf2, Klf4, and Klf5), the Myc family (c-myc, L-myc, and N-myc), Nanog, and LIN28, have been identified to increase the induction efficiency.


title: Induced pluripotent stem cell

text: Although the methods pioneered by Yamanaka and others have demonstrated that adult cells can be reprogrammed to iPS cells, there are still challenges associated with this technology:


title: Induced pluripotent stem cell

text: The table on the right summarizes the key strategies and techniques used to develop iPS cells in the first five years after Yamanaka et al.'s 2006 breakthrough. Rows of similar colors represent studies that used similar strategies for reprogramming.


title: Induced pluripotent stem cell

text: One of the main strategies for avoiding problems (1) and (2) has been to use small molecules that can mimic the effects of transcription factors. These compounds can compensate for a reprogramming factor that does not effectively target the genome or fails at reprogramming for another reason; thus they raise reprogramming efficiency. They also avoid the problem of genomic integration, which in some cases contributes to tumor genesis. Key studies using such strategy were conducted in 2008. Melton et al. studied the effects of histone deacetylase (HDAC) inhibitor valproic acid. They found that it increased reprogramming efficiency 100-fold (compared to Yamanaka's traditional transcription factor method). The researchers proposed that this compound was mimicking the signaling that is usually caused by the transcription factor c-Myc. A similar type of compensation mechanism was proposed to mimic the effects of Sox2. In 2008, Ding et al. used the inhibition of histone methyl transferase (HMT) with BIX-01294 in combination with the activation of calcium channels in the plasma membrane in order to increase reprogramming efficiency. Deng et al. of Beijing University reported in July 2013 that induced pluripotent stem cells can be created without any genetic modification. They used a cocktail of seven small-molecule compounds including DZNep to induce the mouse somatic cells into stem cells which they called CiPS cells with the efficiency – at 0.2% – comparable to those using standard iPSC production techniques. The CiPS cells were introduced into developing mouse embryos and were found to contribute to all major cells types, proving its pluripotency.


title: Induced pluripotent stem cell

text: Ding et al. demonstrated an alternative to transcription factor reprogramming through the use of drug-like chemicals. By studying the MET (mesenchymal-epithelial transition) process in which fibroblasts are pushed to a stem-cell like state, Ding's group identified two chemicals – ALK5 inhibitor SB431412 and MEK (mitogen-activated protein kinase) inhibitor PD0325901 – which was found to increase the efficiency of the classical genetic method by 100 fold. Adding a third compound known to be involved in the cell survival pathway, further increases the efficiency by 200 fold. Using the combination of these three compounds also decreased the reprogramming process of the human fibroblasts from four weeks to two weeks.


title: Induced pluripotent stem cell

text: In April 2009, it was demonstrated that generation of iPS cells is possible without any genetic alteration of the adult cell: a repeated treatment of the cells with certain proteins channeled into the cells via poly-arginine anchors was sufficient to induce pluripotency. The acronym given for those iPSCs is piPSCs (protein-induced pluripotent stem cells).


title: Induced pluripotent stem cell

text: Another key strategy for avoiding problems such as tumorgenesis and low throughput has been to use alternate forms of vectors: adenovirus, plasmids, and naked DNA and/or protein compounds.


title: Induced pluripotent stem cell

text: In 2008, Hochedlinger et al. used an adenovirus to transport the requisite four transcription factors into the DNA of skin and liver cells of mice, resulting in cells identical to ESCs. The adenovirus is unique from other vectors like viruses and retroviruses because it does not incorporate any of its own genes into the targeted host and avoids the potential for insertional mutagenesis. In 2009, Freed et al. demonstrated successful reprogramming of human fibroblasts to iPS cells. Another advantage of using adenoviruses is that they only need to present for a brief amount of time in order for effective reprogramming to take place.


title: Induced pluripotent stem cell

text: Also in 2008, Yamanaka et al. found that they could transfer the four necessary genes with a plasmid. The Yamanaka group successfully reprogrammed mouse cells by transfection with two plasmid constructs carrying the reprogramming factors; the first plasmid expressed c-Myc, while the second expressed the other three factors (Oct4, Klf4, and Sox2). Although the plasmid methods avoid viruses, they still require cancer-promoting genes to accomplish reprogramming. The other main issue with these methods is that they tend to be much less efficient compared to retroviral methods. Furthermore, transfected plasmids have been shown to integrate into the host genome and therefore they still pose the risk of insertional mutagenesis. Because non-retroviral approaches have demonstrated such low efficiency levels, researchers have attempted to effectively rescue the technique with what is known as the PiggyBac Transposon System. Several studies have demonstrated that this system can effectively deliver the key reprogramming factors without leaving footprint mutations in the host cell genome. The PiggyBac Transposon System involves the re-excision of exogenous genes, which eliminates the issue of insertional mutagenesis.


title: Induced pluripotent stem cell

text: In January 2014, two articles were published claiming that a type of pluripotent stem cell can be generated by subjecting the cells to certain types of stress (bacterial toxin, a low pH of 5.7, or physical squeezing); the resulting cells were called STAP cells, for stimulus-triggered acquisition of pluripotency.


title: Induced pluripotent stem cell

text: In light of difficulties that other labs had replicating the results of the surprising study, in March 2014, one of the co-authors has called for the articles to be retracted. On 4 June 2014, the lead author, Obokata agreed to retract both the papers after she was found to have committed 'research misconduct' as concluded in an investigation by RIKEN on 1 April 2014.


title: Induced pluripotent stem cell

text: MicroRNAs are short RNA molecules that bind to complementary sequences on messenger RNA and block expression of a gene. Measuring variations in microRNA expression in iPS cells can be used to predict their differentiation potential. Addition of microRNAs can also be used to enhance iPS potential. Several mechanisms have been proposed. ES cell-specific microRNA molecules (such as miR-291, miR-294 and miR-295) enhance the efficiency of induced pluripotency by acting downstream of c-Myc. microRNAs can also block expression of repressors of Yamanaka's four transcription factors, and there may be additional mechanisms induce reprogramming even in the absence of added exogenous transcription factors.


title: Induced pluripotent stem cell

text: Induced pluripotent stem cells are similar to natural pluripotent stem cells, such as embryonic stem cells, in many aspects, such as the expression of certain stem cell genes and proteins, chromatin methylation patterns, doubling time, embryoid body formation, teratoma formation, viable chimera formation, and potency and differentiability, but the full extent of their relation to natural pluripotent stem cells is still being assessed.


title: Induced pluripotent stem cell

text: Gene expression and genome-wide H3K4me3 and H3K27me3 were found to be extremely similar between ES and iPS cells. The generated iPSCs were remarkably similar to naturally isolated pluripotent stem cells (such as mouse and human embryonic stem cells, mESCs and hESCs, respectively) in the following respects, thus confirming the identity, authenticity, and pluripotency of iPSCs to naturally isolated pluripotent stem cells:


title: Induced pluripotent stem cell

text: Recent achievements and future tasks for safe iPSC-based cell therapy are collected in the review of Okano et al.


title: Induced pluripotent stem cell

text: The task of producing iPS cells continues to be challenging due to the six problems mentioned above. A key tradeoff to overcome is that between efficiency and genomic integration. Most methods that do not rely on the integration of transgenes are inefficient, while those that do rely on the integration of transgenes face the problems of incomplete reprogramming and tumor genesis, although a vast number of techniques and methods have been attempted. Another large set of strategies is to perform a proteomic characterization of iPS cells. Further studies and new strategies should generate optimal solutions to the five main challenges. One approach might attempt to combine the positive attributes of these strategies into an ultimately effective technique for reprogramming cells to iPS cells.


title: Induced pluripotent stem cell

text: Another approach is the use of iPS cells derived from patients to identify therapeutic drugs able to rescue a phenotype. For instance, iPS cell lines derived from patients affected by ectodermal dysplasia syndrome (EEC), in which the p63 gene is mutated, display abnormal epithelial commitment that could be partially rescued by a small compound.


title: Induced pluripotent stem cell

text: An attractive feature of human iPS cells is the ability to derive them from adult patients to study the cellular basis of human disease. Since iPS cells are self-renewing and pluripotent, they represent a theoretically unlimited source of patient-derived cells which can be turned into any type of cell in the body. This is particularly important because many other types of human cells derived from patients tend to stop growing after a few passages in laboratory culture. iPS cells have been generated for a wide variety of human genetic diseases, including common disorders such as Down syndrome and polycystic kidney disease. In many instances, the patient-derived iPS cells exhibit cellular defects not observed in iPS cells from healthy subjects, providing insight into the pathophysiology of the disease. An international collaborated project, StemBANCC, was formed in 2012 to build a collection of iPS cell lines for drug screening for a variety of disease. Managed by the University of Oxford, the effort pooled funds and resources from 10 pharmaceutical companies and 23 universities. The goal is to generate a library of 1,500 iPS cell lines which will be used in early drug testing by providing a simulated human disease environment. Furthermore, combining hiPSC technology and small molecule or genetically encoded voltage and calcium indicators provided a large-scale and high-throughput platform for cardiovascular drug safety screening.


title: Induced pluripotent stem cell

text: A proof-of-concept of using induced pluripotent stem cells (iPSCs) to generate human organ for transplantation was reported by researchers from Japan. Human 'liver buds' (iPSC-LBs) were grown from a mixture of three different kinds of stem cells: hepatocytes (for liver function) coaxed from iPSCs; endothelial stem cells (to form lining of blood vessels) from umbilical cord blood; and mesenchymal stem cells (to form connective tissue). This new approach allows different cell types to self-organize into a complex organ, mimicking the process in fetal development. After growing "in vitro" for a few days, the liver buds were transplanted into mice where the 'liver' quickly connected with the host blood vessels and continued to grow. Most importantly, it performed regular liver functions including metabolizing drugs and producing liver-specific proteins. Further studies will monitor the longevity of the transplanted organ in the host body (ability to integrate or avoid rejection) and whether it will transform into tumors. Using this method, cells from one mouse could be used to test 1,000 drug compounds to treat liver disease, and reduce animal use by up to 50,000.


title: Induced pluripotent stem cell

text: In 2021, a switchable Yamanaka factors-reprogramming-based approach for regeneration of damaged heart without tumor-formation was demonstrated in mice and was successful if the intervention was carried out immediately before or after a heart attack.


title: Induced pluripotent stem cell

text: Embryonic cord-blood cells were induced into pluripotent stem cells using plasmid DNA. Using cell surface endothelial/pericytic markers CD31 and CD146, researchers identified 'vascular progenitor', the high-quality, multipotent vascular stem cells. After the iPS cells were injected directly into the vitreous of the damaged retina of mice, the stem cells engrafted into the retina, grew and repaired the vascular vessels.


title: Induced pluripotent stem cell

text: Labelled iPSCs-derived NSCs injected into laboratory animals with brain lesions were shown to migrate to the lesions and some motor function improvement was observed.


title: Induced pluripotent stem cell

text: Beating cardiac muscle cells, iPSC-derived cardiomyocytes, can be mass-produced using chemically defined differentiation protocols. These protocols typically modulate the same developmental signaling pathways required for heart development . These iPSC-cardiomyocytes can recapitulate genetic arrhythmias and cardiac drug responses, since they exhibit the same genetic background as the patient from which they were derived.


title: Induced pluripotent stem cell

text: In June 2014, Takara Bio received technology transfer from iHeart Japan, a venture company from Kyoto University's iPS Cell Research Institute, to make it possible to exclusively use technologies and patents that induce differentiation of iPS cells into cardiomyocytes in Asia. The company announced the idea of selling cardiomyocytes to pharmaceutical companies and universities to help develop new drugs for heart disease.


title: Induced pluripotent stem cell

text: On March 9, 2018, the Specified Regenerative Medicine Committee of Osaka University officially approved the world's first clinical research plan to transplant a "myocardial sheet" made from iPS cells into the heart of patients with severe heart failure. Osaka University announced that it had filed an application with the Ministry of Health, Labor and Welfare on the same day.


title: Induced pluripotent stem cell

text: On May 16, 2018, the clinical research plan was approved by the Ministry of Health, Labor and Welfare's expert group with a condition.


title: Induced pluripotent stem cell

text: In October 2019, a group at Okayama University developed a model of ischemic heart disease using cardiomyocytes differentiated from iPS cells.


title: Induced pluripotent stem cell

text: Although a pint of donated blood contains about two trillion red blood cells and over 107 million blood donations are collected globally, there is still a critical need for blood for transfusion. In 2014, type O red blood cells were synthesized at the Scottish National Blood Transfusion Service from iPSC. The cells were induced to become a mesoderm and then blood cells and then red blood cells. The final step was to make them eject their nuclei and mature properly. Type O can be transfused into all patients. Human clinical trials were not expected to begin before 2016.


title: Induced pluripotent stem cell

text: The first human clinical trial using autologous iPSCs was approved by the Japan Ministry Health and was to be conducted in 2014 at the Riken Center for Developmental Biology in Kobe. However the trial was suspended after Japan's new regenerative medicine laws came into effect in November 2015. More specifically, an existing set of guidelines was strengthened to have the force of law (previously mere recommendations). iPSCs derived from skin cells from six patients with wet age-related macular degeneration were reprogrammed to differentiate into retinal pigment epithelial (RPE) cells. The cell sheet would be transplanted into the affected retina where the degenerated RPE tissue was excised. Safety and vision restoration monitoring were to last one to three years.


title: Induced pluripotent stem cell

text: In March 2017, a team led by Masayo Takahashi completed the first successful transplant of iPS-derived retinal cells from a donor into the eye of a person with advanced macular degeneration. However it was reported that they are now having complications. The benefits of using autologous iPSCs are that there is theoretically no risk of rejection and that it eliminates the need to use embryonic stem cells. However, these iPSCs were derived from another person.


title: Induced pluripotent stem cell

text: New clinical trials involving iPSCs are now ongoing not only in Japan, but also in the US and Europe. Research in 2021 on the trial registry Clinicaltrials.gov identified 129 trial listings mentioning iPSCs, but most were non-interventional.


title: Induced pluripotent stem cell

text: To make iPSC-based regenerative medicine technologies available to more patients, it is necessary to create universal iPSCs that can be transplanted independently of haplotypes of HLA. The current strategy for the creation of universal iPSCs has two main goals: to remove HLA expression and to prevent NK cells attacks due to deletion of HLA. Deletion of the B2M and CIITA genes using the CRISPR/Cas9 system has been reported to suppress the expression of HLA class I and class II, respectively. To avoid NK cell attacks. transduction of ligands inhibiting NK-cells, such as HLA-E and CD47 has been used. HLA-C is left unchanged, since the 12 common HLA-C alleles are enough to cover 95% of the world's population.


title: Induced pluripotent stem cell

text: A multipotent mesenchymal stem cell, when induced into pluripotence, holds great promise to slow or reverse aging phenotypes. Such anti-aging properties were demonstrated in early clinical trials in 2017. In 2020, Stanford University researchers concluded after studying elderly mice that old human cells when subjected to the Yamanaka factors, might rejuvenate and become nearly indistinguishable from their younger counterparts.


title: Hermanos (Breaking Bad)

text: "Hermanos" is the eighth episode of the fourth season of the American television drama series "Breaking Bad", and the 41st overall episode of the series. It originally aired on AMC in the United States on September 4, 2011.


title: Hermanos (Breaking Bad)

text: During a pre-credits flashback, right after the deaths of Leonel and Marco Salamanca and Juan Bolsa, Gus Fring meets with Hector Salamanca and hints that he orchestrated Leonel and Marco's deaths out of revenge, phrasing "blood for blood", which then seems to infuriate the immobile Hector.


title: Hermanos (Breaking Bad)

text: Gus is called to meet with the police and DEA, where he is asked about his fingerprints in Gale Boetticher's apartment. He explains that Gale was a recipient years ago of a UNM college scholarship in chemistry that Gus created, and says that Gale had invited Gus to his apartment for dinner to ask him for money. Hank Schrader asks if Gus Fring is his real name, as there are no records of anyone with that name in his native Chile. Gus says he immigrated at the time of Pinochet's dictatorship, which he claims was notorious both for human rights violations and poor record-keeping. The investigators are satisfied with his answers, except Hank, who is still suspicious. Meanwhile, Skyler White begins to hide Walter White's meth money in a crawl space below the house.


title: Hermanos (Breaking Bad)

text: Hank later asks Walter to drive him to a mineral show, but reveals "en route" that he is really going to Los Pollos Hermanos to plant a GPS tracking unit on Gus' car. Walter is nervous since he is already on poor terms with Gus and because Mike Ehrmantraut has appeared and is watching him, but Walter ultimately gives in to Hank. Walter pretends to plant the tracker and goes inside the restaurant, where Gus meets him at a register. Walter hastens to assure Gus that he did not plant the tracker, showing it still in his pocket, but Gus tells him to "do it." Perplexed, Walter plants the tracker on his way back to his car and leaves with Hank. Later, Walter (on video) and Mike each assure Gus that Hank is acting on his own and not as part of the DEA's investigation, but Mike advises Gus that Hank may pose a problem if Gus and the cartel go to war. Walter warns Jesse Pinkman about Hank's investigation and again urges him to kill Gus. While at Jesse's house, Walter intercepts a text message meant for Jesse and suspects that Jesse is becoming loyal to Gus.


title: Hermanos (Breaking Bad)

text: Gus goes to see Hector in the nursing home and asks him, cryptically, if today is the day. A flashback to 1989 in Mexico shows Gus and Max, his business partner and boyfriend, meeting with Hector, Bolsa, and their boss, Don Eladio. Gus and Max pitch their meth scheme to Eladio in hopes of going into business with the cartel. Max, who is a biochemist and chemical engineer, produces the meth, and the pair sell it out of their restaurant, named Los Pollos Hermanos after Gus and Max. Although Eladio likes the idea, he feels Gus has disrespected him by giving meth "samples" to Eladio's henchmen in order to manipulate him into a meeting. Moreover, Eladio wonders what Gus' purpose is in the business if Max is the cook of the high-grade meth. Before Gus can explain, Hector shoots Max through the head and forces Gus to lie down and look his dead partner in the eyes. Eladio tells Gus that the only reason Gus is alive and Max is not is because Eladio knows who Gus really is, and warns him that he is "not in Chile anymore." In the present day, Gus tells Hector to look him in the eyes, but Hector refuses. "Maybe next time," Gus says, and leaves.


title: Hermanos (Breaking Bad)

text: "Hermanos" was the first episode to delve into Gus Fring's backstory, although much remains unexplained about the character's past in Chile, which Gus seems anxious to keep concealed. Series creator Vince Gilligan has said Gus was likely involved in the military dictatorship of General Augusto Pinochet, but the writing staff had deliberately not determined the entire backstory. Gilligan said he believed this would make Gus a more interesting and mysterious character, while simultaneously allowing the writers greater flexibility in writing for him in future episodes.


title: Hermanos (Breaking Bad)

text: The episode received critical acclaim. Alan Sepinwall of HitFix praised the episode, describing it as "another superb hour of season 4". Seth Amitin of IGN gave it a rare 10 out of 10. Donna Bowman of "The A.V. Club" gave the episode a "B+".


title: Hermanos (Breaking Bad)

text: Emmy nominee Giancarlo Esposito submitted this episode for consideration for the Primetime Emmy Award for Outstanding Supporting Actor in a Drama Series for the 64th Primetime Emmy Awards. He ultimately lost to Aaron Paul for his performance in the episode "End Times".


title: Opium den

text: An opium den was an establishment in which opium was sold and smoked. Opium dens were prevalent in many parts of the world in the 19th century, most notably China, Southeast Asia, North America, and France. Throughout the West, opium dens were frequented by and associated with the Chinese because the establishments were usually run by Chinese mobsters, who supplied the opium and prepared it for visiting non-Chinese smokers. Most opium dens kept a supply of opium paraphernalia such as the pipes and lamps that were necessary to smoke the drug. Patrons would recline to hold the long opium pipes over oil lamps that would heat the drug until it vaporized, allowing the smoker to inhale the vapors. Opium dens in China were frequented by all levels of society, and their opulence or simplicity reflected the financial means of the patrons. In urban areas of the United States, particularly on the West Coast, there were opium dens that mirrored the best to be found in China, with luxurious trappings and female attendants. For the working class, there were many low-end dens with sparse furnishings.


title: Opium den

text: Opium smoking arrived in North America with the large influx of Chinese, who came to participate in the California Gold Rush. The jumping-off point for the gold fields was San Francisco, and the city's Chinatown became the site of numerous opium dens soon after the first Chinese arrived, around 1850. However, from 1863 to the end of the century, anti-vice laws imposed by the new municipal code book banned visiting opium rooms in addition to prostitution. Despite this, the 1870s attracted many non-Chinese residents to San Francisco's dens, prompting the city fathers to enact the nation's first anti-drug law, an 1875 ordinance banning opium dens. In the early 20th century, huge bonfires, fueled by confiscated opium and opium paraphernalia, were used to destroy opium and create a public venue to discuss opium use.


title: Opium den

text: Opium-eradication campaigns drove opium smoking underground, but it was still fairly common in San Francisco and other North American cities until around World War II. A typical opium den in San Francisco might have been a Chinese-run laundry that had a basement, back room, or upstairs room that was tightly sealed to keep drafts from making the opium lamps flicker or allowing the tell-tale opium fumes to escape. A photograph of one luxurious opium den in 19th-century San Francisco has survived, taken by I. W. Taber in 1886, but the majority of the city's wealthy opium smokers, both Chinese and non-Chinese, shunned public opium dens in favor of smoking in the privacy of their own homes.


title: Opium den

text: The opium dens of New York City's Chinatown, due to its geographical distance from China, were not as opulent as some of those to be found on the American West Coast. According to H. H. Kane, a doctor who spent years studying opium use in New York in the 1870s and 1880s, the most popular opium dens (or "opium joints" as they were known in the parlance of the day) were located on Mott and Pell Streets in Chinatown. At the time, all the city's opium dens were run by Chinese, except for one on 23rd Street that was run by an American woman and her two daughters. Kane remarked that New York's opium dens were one place "where all nationalities seem indiscriminately mixed".


title: Opium den

text: As in San Francisco, New Yorkers of all races would come to Chinatown to patronize its opium dens. New York City's last known opium den was raided and shut down on June 28, 1957.


title: Opium den

text: Chinese immigrants first established Chinatowns in Victoria and Vancouver in British Columbia, and here too, opium dens were common in the late 19th and early 20th centuries. When the city of San Francisco began taxing imported opium for smoking, the trade was diverted to Victoria, and, from there, much of the opium was smuggled south into the United States. However, a fair amount of opium was consumed in the opium dens to be found in the Chinatowns of Victoria and Vancouver. The latter city's "Shanghai Alley" was known for its rustic opium dens. As in the United States, non-Chinese often frequented the Chinese-run opium dens in Canadian Chinatowns.


title: Opium den

text: Opium smoking in France was introduced for the most part by French expatriates returning home from stints in their Indochinese colonies. By the early 20th century, there were numerous opium dens in France's port cities, particularly Toulon, Marseille and Hyères.


title: Opium den

text: Victorian London's reputation as a centre of opium smoking is based on literary fiction rather than historical fact. The London press, along with popular British authors of the day, were fond of portraying London's Limehouse district as an opium-drenched pit of danger and mystery. In fact, London's Chinese population never exceeded the low hundreds, in large contrast to the tens of thousands of Chinese who settled in North American Chinatowns. In the mid-1880s, Chinatowns started to form in London and Liverpool with grocery stores, eating houses, meeting places and, in the East End, Chinese street names. In 1891, the Census recorded 582 Chinese-born residents in Britain, though this dropped to 387 in 1896. 80% were single males between 20 and 35, the majority being seamen. Companies began to export opium from India to China, selling the drug to raise the money to buy shipments of tea. This was against Chinese law and angered China's authorities. In 1839, war broke out between Britain and China over the opium trade. Britain defeated China and under the terms of the Treaty of Nanking in 1842, Hong Kong became a British colony. In 1857, the Second Opium War resulted in the Treaties of Tianjin which included a clause allowing Britain and France to recruit Chinese to the British Colonies, North America, South America, and Australia as cheap labour. However, Britain did not recruit as many workers as North America, where the Chinese were employed on the construction of the Transcontinental Railroad, and where many Chinese immigrated in search of fortune during the gold rush, thus the Chinese communities were much smaller in Britain. The Chinese immigrants to London often arrived in the East London ports by boat, such as the Blue Funnel Line. Most of them were seamen, and many would have settled in only a few select streets. When jobs on the docks and on boats dried up, many Chinese turned to other businesses, such as the restaurants or laundries.


title: Opium den

text: In the 1860s, "Dark England" with its opium dens in London's East End was described in popular press and books, various individuals and religious organisations began to campaign against unrestricted opium trafficking. At Pennyfields there was a Christian Mission for the Chinese and a Confucian temple. At Limehouse Causeway there was the famous Ah Tack's lodging house. There was much prejudice against the East End Chinese community, with much of it initiated by the writings of Thomas Burke and Sax Rohmer. Both of these men wrote about the Chinese community. Burke and Ward exaggerated the Chinese community's true size and made much mention of gambling, opium dens, and "unholy things" in the shadows. A character from Charles Dickens' last novel, "The Mystery of Edwin Drood" (1870) sets the scene: "O my poor head! I makes my pipes of old penny ink-bottles, ye see, deary – this is one – and I fits-in a mouthpiece, this way,


title: Opium den

text: and I takes my mixter out of this thimble with this little horn spoon; and so I fills, deary. Ah, my poor nerves!"


title: Opium den

text: Dickens is famous for his portrayal and caricature of nineteenth-century London. So it is significant that he has immortalised this opium den in east London, identifying it as part of the fabric-weave of Victorian London. The establishment "run by the Chinaman" described in "The Mystery of Edwin Drood", was based on a real opium den. It was run by Ah Sing, or John Johnston as he was known to his clients, an immigrant from Amoy in China. Rare photographs of the Chinese opium scene in East London do exist. A photograph held at the Science Museum in London shows two Chinese women outside Ah Sing's opium den. Ah Sing was a smoker himself, and it was claimed that only he had the "true secret of mixing opium ... with an eye to business". His secret evidently brought him much success, as his den was frequented by the local Chinese sailors on a break from working on the ships, but also others. Some literary elite of the time including Arthur Conan Doyle (see "The Man with the Twisted Lip") and Dickens himself visited the area, although whether they themselves took up the "pipe" has remained undisclosed. Ah Sing's opium den was probably the most famous of the dens in Victorian London, attracting gentlemen from the very elite of London's high society.


title: Opium den

text: In 1868, the Pharmacy Act recognised dangerous drugs and limited their sale to registered chemists and pharmacists, but until the end of the nineteenth century few doctors and scientists warned about the dangers of drug addiction. When the small number of opium dens gradually declined in London, following crackdowns from the authorities, individuals like Ah Sing were forced to move from their properties, and had to find alternative ways of making a living. In his latter days, it was said that he continued to smoke, despite finding religion. He did eventually manage to give up opium smoking, though only days before he died around 1890, aged 64. He is now buried in Bow Cemetery.


title: Coulomb constant

text: The Coulomb constant, the electric force constant, or the electrostatic constant (denoted , or ) is a proportionality constant in electrostatics equations. In SI base units it is equal to . It was named after the French physicist Charles-Augustin de Coulomb (1736–1806) who introduced Coulomb's law.


title: Coulomb constant

text: Taking this integral for a sphere, radius , centered on a point charge, the electric field points radially outwards and is normal to a differential surface element on the sphere with constant magnitude for all points on the sphere.


title: Coulomb constant

text: Coulomb's law is an inverse-square law, and thereby similar to many other scientific laws ranging from gravitational pull to light attenuation. This law states that a specified physical quantity is inversely proportional to the square of the distance.formula_5In some modern systems of units, the Coulomb constant has an exact numeric value; in Gaussian units , in Heaviside–Lorentz units (also called "rationalized") . This was previously true in SI when the vacuum permeability was defined as . Together with the speed of light in vacuum , defined as , the vacuum permittivity can be written as , which gave an exact value of


title: Coulomb constant

text: Since the redefinition of SI base units, the Coulomb constant is no longer exactly defined and is subject to the measurement error in the fine structure constant, as calculated from CODATA 2018 recommended values being


title: Coulomb constant

text: The Coulomb constant is used in many electric equations, although it is sometimes expressed as the following product of the vacuum permittivity constant:


title: Sa'ar 6-class corvette

text: The Sa'ar 6-class corvette is a series of four German-made corvettes ordered for the Israeli Navy in May 2015.


title: Sa'ar 6-class corvette

text: The ships' design is loosely based on the German , but with engineering changes to accommodate Israeli-built sensors and missiles such as the Barak 8 and the naval Iron Dome system. Elbit Systems has been awarded the contract to design and build the electronic warfare (EW) suites for the ships.


title: Sa'ar 6-class corvette

text: All four vessels were constructed in Germany in a joint project by German Naval Yards Holdings and ThyssenKrupp Marine Systems. The first of the class was scheduled to be delivered in 2020. Construction cost was estimated at NIS 1.8 billion Israeli new shekel (NIS) or roughly 430 million Euros ($480 million). Israel will pay for two thirds of the cost and the German Government will subsidize a third of the corvettes' construction costs, as with the s.


title: Sa'ar 6-class corvette

text: The Lebanese Hezbollah group alleges that Israel's gas fields lie in Lebanese waters. It has threatened to target Israeli gas platforms. An Israeli-owned ship reportedly came under missile fire repeatedly near the United Arab Emirates. The ship was en route to the UAE from Kuwait, according to Channel 12 news.


title: Sa'ar 6-class corvette

text: The Sa'ar 6 has been adopted for maritime protection, anti-shipping and prevent threats in the Israeli exclusive economic zone (EEZ).The Sa'ar 6 is also used to defend Israeli shipping lanes in the Mediterranean to import more than 90 percent of goods for Israel. One of their roles will be to protect natural gas platforms in the Mediterranean Sea against possible sea-borne, counter-terrorism or rocket threats.


title: Sa'ar 6-class corvette

text: The Sa'ar 6 has a displacement of almost 1,900 tons at full load and is long. It is armed with an Oto Melara 76 mm main gun, two Typhoon Weapon Stations, 16 vertical launch cells for Barak-8 surface-to-air missiles, 40 cells for the C-Dome point defense system, 16 anti-ship missiles Gabriel V, the EL/M-2248 MF-STAR AESA radar, and two torpedo launchers. It has hangar space and a platform able to accommodate a medium class SH-60-type helicopter.


title: Sa'ar 6-class corvette

text: Israel received the first of four Sa'ar 6-class corvettes, , on 11 December 2020; Thyssen Krupp Marine Systems officially handed over the second corvette, , on 4 May 2021. On July 27, 2021, the final two ships, "INS Atzmaut" and "INS Nitzachon", were also delivered to the Israeli Navy by the builder. They were to be equipped with radar and weapon systems by the Israeli Navy after their arrival in Israel. In Haifa in September 2022, the vessel's 76/62 rapid-fire main gun was ceremonially accepted for the first two ships of the class.


title: Deval Patrick

text: Deval Laurdine Patrick (born July 31, 1956) is an American politician, civil rights lawyer, author, and businessman who served as the 71st governor of Massachusetts from 2007 to 2015. He was first elected in 2006, succeeding Mitt Romney, who chose not to run for reelection to focus on his 2008 presidential campaign. He was reelected in 2010. He was the first African-American Governor of Massachusetts and the first Democratic Governor of the state in 16 years since Michael Dukakis left office in 1991. Patrick served from 1994 to 1997 as the United States Assistant Attorney General for the Civil Rights Division under President Bill Clinton. He was briefly a candidate for President of the United States in the 2020 U.S. presidential election.


title: Deval Patrick

text: Raised largely by a single mother on the South Side of Chicago, Patrick earned a scholarship to Milton Academy in Milton, Massachusetts in the eighth grade. He went on to attend Harvard College and Harvard Law School. After graduating, he practiced law with the NAACP Legal Defense and Educational Fund and later joined a Boston law firm, where he was named a partner at age 34. In 1994, Bill Clinton appointed him as the United States assistant attorney general for the civil rights division of the United States Department of Justice, where he worked on issues including racial profiling and police misconduct.


title: Deval Patrick

text: During his governorship, Patrick oversaw the implementation of the state's 2006 health care reform program which had been enacted under Mitt Romney, increased funding to education and life sciences, won a federal Race to the Top education grant, passed an overhaul of governance of the state transportation function, signing a law to create the Massachusetts Department of Transportation, increased the state sales tax from 5% to 6.25%, raised the state's minimum wage from $8 per hour to $11 by 2017, and planned the introduction of casinos to the state. Under Patrick, Massachusetts joined the Regional Greenhouse Gas Initiative (RGGI) in an effort to reduce greenhouse gas emissions. Shortly after Patrick's second term began on January 6, 2011, he declared he would not seek re-election in 2014.


title: Deval Patrick

text: Patrick is a managing director at Bain Capital and serves as the chairman of the board for Our Generation Speaks, a fellowship program and startup incubator whose mission is to bring together young Israeli and Palestinian leaders through entrepreneurship. He also holds a Board of Directors position at telehealth company American Well.


title: Deval Patrick

text: Members of his own inner circle and Barack Obama's inner circle encouraged Patrick to run for president in 2020, but Patrick ruled out a 2020 presidential bid in December 2018. In November 2019, however, uneasy about the existing field of Democratic candidates, Patrick was reported to have called a few leading Democrats and allies to say that he would soon announce a 2020 presidential bid. He formally entered the race on November 14, 2019. He ended his campaign on February 12, 2020, following a very poor showing in the Iowa caucus and the New Hampshire primary.


title: Deval Patrick

text: Patrick was born on July 31, 1956 in the South Side of Chicago, where his family resided in a two-bedroom apartment in the Robert Taylor Homes' housing projects. Patrick is the son of Emily Mae ("née" Wintersmith) and Pat Patrick, a jazz musician associated with Sun Ra. In 1959, Patrick's father abandoned their family in order to play music in New York City, and because he had fathered a daughter, La'Shon Anthony, by another woman. Deval reportedly had a strained relationship with his father, who opposed his choice of high school, but they eventually reconciled. Patrick was raised by his mother, who traces her roots to American slaves in Kentucky.


title: Deval Patrick

text: While Patrick was in middle school, one of his teachers referred him to A Better Chance, a national non-profit organization for identifying, recruiting and developing leaders among academically gifted minority students, which enabled him to attend Milton Academy in Milton, Massachusetts. Patrick graduated from Milton Academy in 1974 and went on to attend college, the first in his family. He graduated from Harvard College, where he was a member of the Fly Club, with a Bachelor of Arts degree, "cum laude," in English and American literature, in 1978. At Harvard, Patrick won "Best Oralist" in the Ames Moot Court Competition, in 1981.


title: Deval Patrick

text: Patrick graduated from Harvard Law School with a J.D., "cum laude," in 1982. He proceeded to fail the State Bar of California exam twice, before passing on his third try. Patrick then served as a law clerk to Judge Stephen Reinhardt on the United States Court of Appeals for the Ninth Circuit for one year. In 1983, he joined the staff of the NAACP Legal Defense Fund (LDF), where he worked on death penalty and voting rights cases.


title: Deval Patrick

text: While at LDF, he met Bill Clinton, the then Governor of Arkansas, when he sued Clinton in a voting case. In 1986, he joined the Boston law firm of Hill & Barlow and was named partner in 1990, at the age of 34. While at Hill & Barlow, he managed high-profile engagements such as acting as Desiree Washington's attorney in her civil lawsuit against Mike Tyson.


title: Deval Patrick

text: In 1994, President Bill Clinton nominated Patrick as the United States Assistant Attorney General for the Civil Rights Division, and he was subsequently confirmed by the United States Senate. Federal affirmative action policy was under judicial and political review, and Patrick defended Clinton's policy. Patrick also worked on issues including racial profiling, police misconduct, and the treatment of incarcerated criminals."


title: Deval Patrick

text: Between 1995 and 1997, Patrick coordinated an investigation into a series of arsons of predominantly black churches across the South. The investigation brought together a number of state and federal agencies, and was the largest federal investigation in history until the time of 9/11. In the end, more than 100 arrests were made, but no evidence of national or regional conspiracy was found.


title: Deval Patrick

text: In 1997, Patrick returned to Boston to join the firm of Day, Berry & Howard (later called Day Pitney LLP), and was appointed by the federal district court to serve as Chairman of Texaco's Equality and Fairness Task Force to oversee implementation of the terms of a race discrimination settlement. Working with employees at all levels, Patrick and his Task Force examined and reformed Texaco's complex corporate employment culture, and created a model for fostering an equitable workplace.


title: Deval Patrick

text: Some gay rights activists criticized him for his tenure on the United Airlines (UAL) board. During this time, the company originally fought an ordinance requiring that it offer domestic partnership benefits, but Patrick successfully encouraged UAL to offer such benefits to all employees, making it the first airline to do so.


title: Deval Patrick

text: In 1999, partly because of his work on the Equality and Fairness Task Force, Patrick was offered the job as General Counsel of Texaco, responsible for all of the company's legal affairs. While he continued his work transforming employment practices at the company, the majority of his time was devoted to exploring and working out a merger, ultimately announced in October 2000, with larger Chevron Corp.


title: Deval Patrick

text: In 2001, Patrick left Texaco to become the Executive Vice-President, General Counsel and Secretary at The Coca-Cola Company. Patrick pushed for a thorough review of allegations that some workers at bottlers of Coke products in Colombia had been abused or even killed by paramilitary groups as a result of union organizing activity. Patrick concluded the allegations to be unsubstantiated and untrue, but counseled that the company allow an independent inquiry to lay all questions to rest. After initially supporting Patrick's view, then-CEO Douglas Daft changed his mind, precipitating Patrick's decision to leave Coke.