title: Call Me Maybe

text: "The Village Voice"s Maura Johnston deemed it as an "utterly earwormy" song. "RedEye"s Emily Van Zandt began her review of the track saying, "screw you, Internet. Thanks to a couple of posts on blogs that I refuse to own up to follow, my afternoon has been dedicated to Carly Rae Jepsen's 'Call Me Maybe'." Van Zandt continued to state that "all I know is that I have co-dependency issues when it comes to my music. When it's sad, I'm sad. When it's angry, I'm angry. And when it's ridiculously over-produced, up-tempo bubblegum pop with terrible lyrics on a beautiful day in Chicago when I'm wearing pink pants, I just kind of want to start skipping around handing my number out to random bros, you know?" Jim Farber of the "New York Daily News" said, "In lyrical construction, melodic flourish and instrumental arrangement, 'Maybe' has the urgency and sweep of the greatest teen pop songs ever recorded."


title: Call Me Maybe

text: "Pitchfork" named "Call Me Maybe" the 29th best song of 2012, while "Rolling Stone" named it the 50th greatest single of that year. It was voted the best single of 2012 by "The Village Voice"s 40th annual Pazz & Jop critics' poll. As of April 2017, "Billboard" ranked at number one on list "The Best Chorus of the 21st Century". In September 2021, "Rolling Stone" placed it at number 436 on their 500 Greatest Songs of All Time list. In October 2022, "Variety"s Rachel Seo ranked it as Jepsen's 11th best song, writing: "The chronically catchy track evokes memories of 2012, which, among many things, was the year when Marvel's "The Avengers" debuted in theaters and former President Obama was reelected. Call it overplayed and outdated, but if there was a song that could be considered most likely to bring about world peace, 'Call Me Maybe' might rank second (after John Lennon's 'Imagine')."


title: Call Me Maybe

text: "Call Me Maybe" achieved commercial success in Canada, and later in the United States and around the world. The song is Jepsen's third single to enter the Canadian Hot 100, debuting at number 97 for the week of October 22, 2011. For the week of February 11, 2012, "Call Me Maybe" reached number one in its 17th week on the Canadian Hot 100. By doing so, Jepsen became the fifth Canadian artist ever to reach the top position on the new chart in her home country, after Avril Lavigne, Nelly Furtado, Nikki Yanofsky, and Young Artists for Haiti. Jepsen commented that she feels "ultimately honored to be mentioned among those names. These are all artists I look up to in a big way. I have their music, they've been on my records since I can remember. It's really hard to believe. It's cool because at the same time, it's all that I've all ever been working for." The song has since been certified nine times platinum by Music Canada (MC), for sales of 720,000 units of the track in the country. It spent a total of 74 weeks on the chart.


title: Call Me Maybe

text: In the United States, the song debuted at number 38 on the "Billboard" Hot 100 on the week of March 10, 2012 with 80,000 downloads. The song entered the top ten on the chart the week April 14, 2012 at number ten The song reached number one on the week ending June 23, 2012 and spent nine consecutive weeks at number one on the "Billboard" Hot 100. Jepsen is the first Canadian female artist to have a number one on "Billboard" Hot 100 since Avril Lavigne's "Girlfriend", which reached number one the week of May 5, 2007, making her the first Canadian artist to have a number one in the 2010s. The song is only the fourth song to log seven weeks at number one by an artist from Canada, tied with "Sh-Boom" by the Crew-Cuts, "Informer" by Snow featuring MC Shan, and "(Everything I Do) I Do It for You" by Bryan Adams. Three weeks earlier, it had reached number one on the Digital Songs component chart. The track also reached number one on the Mainstream Top 40 chart. The song is Jepsen's first entry on the "Billboard" charts in the country, which made her the first lead woman since Kesha with her single "Tik Tok" to have her debut single peak at such position. "Call Me Maybe" holds the record for the longest run at number one on the US Hot 100 among female Canadian artists and tied with Percy Faith's 1960 song, "Theme from a Summer Place", for the longest among all Canadian artists. "Call Me Maybe" was certified Diamond by the Recording Industry Association of America (RIAA), becoming third female artist to achieve with her own single and first a Canadian female artist to achieve, and as of August 2015, it has sold 7.6 million copies in the US, making it the country's twelfth all-time best-selling digital single.


title: Call Me Maybe

text: "Call Me Maybe" debuted at number 39 in Australia on the chart issue dated March 18, 2012, and four weeks later, rose to number one. It remained at the top for five consecutive weeks, before falling to number two. The song has since been certified nine-times Platinum by the Australian Recording Industry Association (ARIA), denoting shipments of 630,000 copies. The song also made its debut on the country's chart for the week of March 5, 2012 at number 22, reaching the top position four weeks later. It remained at the top for five consecutive weeks, before falling to number two. By August 2012, "Call Me Maybe" had been certified three-times Platinum by the Recording Industry Association of New Zealand (RIANZ), surpassing digital sales of 45,000 units. "Call Me Maybe" became New Zealand's best selling single in 2012, placed at the top spot by the Recording Industry Association of New Zealand.


title: Call Me Maybe

text: "Call Me Maybe" performed well in Europe also, topping the charts in France, Czech Republic, Denmark, Finland, Hungary, Luxembourg, Poland, Slovakia, Switzerland and the United Kingdom. The song debuted in the Republic of Ireland on March 15, 2012. The song went to number one the following week, March 22, 2012, and stayed consecutively at number one for four weeks. while attaining top three positions in Austria, Belgium (Flanders and Wallonia), Germany, Netherlands, Norway, and Sweden. In the United Kingdom, the song debuted at number one on the UK Singles Chart on April 8, 2012 – for the week ending date April 14, 2012 – selling nearly 107,000 copies in the first week and remaining at the top for four weeks. The song became the third fastest-selling song of 2012 on the UK Singles Chart, behind DJ Fresh and Rita Ora's track "Hot Right Now" and Cheryl's "Call My Name". "Call Me Maybe" remained at number one for a second week on April 15, 2012 – for the week ending date April 21, 2012 – keeping Justin Bieber's "Boyfriend" from reaching such position after outselling it by two to one. In its fourth week on the chart, the song stayed at number one with 99,569 copies sold after three consecutive weeks selling over 100,000 copies. The song became Britain's second best-selling single of 2012, with 1,143,000 copies sold. As of April 2017, "Call Me Maybe" has sold 1.35 million copies in the United Kingdom, making it the 11th biggest-selling song by a woman on the UK Singles Chart.


title: Call Me Maybe

text: The music video for "Call Me Maybe" was written and directed by Ben Knechtel and filmed in British Columbia on October 30, 2011. According to Knechtel, the main idea behind the concept was to have a "twist at the end", trying to get away from the idea of the classic "boy meets a girl" story. The music video was released on March 1, 2012, and has nearly 1.5 billion views on YouTube as of October 2022.


title: Call Me Maybe

text: The video begins with Jepsen spying on her attractive tattooed neighbour (Holden Nowell) as he is working on his lawn. As he takes his shirt off and notices she is staring at him, Jepsen is embarrassed and falls below her window, out of sight. She is reading the books "Love at First Sight (Men in Uniform)" by B. J. Daniels and "Skylar's Outlaw" by Linda Warren. The scene then cuts to her garage, where she is rehearsing the track with her band. Following the rehearsals, her bandmates push her to go and wash her car, where she tries to gain her neighbor's attention with various provocative poses only to fall from the hood of the car. She is briefly knocked out from the fall, during which she dreams of a romance novel-type encounter with her crush against the backdrop of Peggy's Cove. As she comes to, the neighbor then helps her get up and watches the band rehearse the track again. After turning and writing down her telephone number, Jepsen sees her neighbor pass one of her male bandmates (Tavish Crowe) his own number, indicating he is gay, where the very end shows that Jepsen is taken aback by this. The video received three nominations on the 2012 MuchMusic Video Awards in the categories of UR Fave Video, Pop Video of the Year, and Video of the Year.


title: Call Me Maybe

text: In a 2018 interview with iHeartRadio Canada, Nowell said he had regrets about his participation in the video, claiming that he was paid $500 with a promise of additional residuals, but never received "a single penny in royalties". He also expressed misgivings about his role, saying, "I didn't like being known as the gay guy in the 'Call Me Maybe' video. It was just something I wasn't used to". He added that it was initially planned for the character's sexuality to be revealed when he kissed the guitarist, but he objected to this: "I was like, 'I'm going to be completely honest with you. I'm not going to kiss a guy, especially for $500.' I said, 'I really don't think I'm comfortable kissing a guy for a music video [...] I said, 'You know what? What if instead of me kissing a guy at the end of the video, what if I just give a guy my number or something like that?'"


title: Call Me Maybe

text: On March 26, 2012, Jepsen visited WBBM-FM's "Morning Show" and performed two tracks of her EP, "Call Me Maybe" and "Curiosity". Days later, the singer made her US television debut during "The Ellen DeGeneres Show" performing "Call Me Maybe". Emily Exton of "Pop Dust" summarized the performance, writing, "delivering fairly true-to-radio vocals that seemed to overcome any lingering nerves performing for millions of viewers (and your sorta boss?) might bring on, Carly left the security of the mike stand to move beneath the oversized dandelion lights during the final moments of her euphoric head-bobber." She also performed an acoustic version of the song on "Kidd Kraddick in the Morning" and KISS 92.5. On May 2, 2012, on a visit to Australia, she performed "Call Me Maybe" on the TV show "Sunrise". On May 20, 2012, Jepsen performed the track on the 2012 "Billboard" Music Awards. On June 9, 2012, Jepsen performed the track with Justin Bieber on the Capital FM Summertime Ball at the Wembley Stadium, London.


title: Call Me Maybe

text: On June 17, 2012, Jepsen performed the song at 2012 MuchMusic Video Awards. On July 22, 2012, Jepsen performed the song at 2012 Teen Choice Awards. She also performed the song on CBBC show "Friday Download" on April 27, 2012, even though the show is pre-recorded. On August 26, 2012, Jepsen performed the song live at the US Open Arthur Ashe Kids' Day, in what began as a pro-am doubles tennis match (Mardy Fish and Jepsen vs. Novak Djokovic and Olympic swimmer Missy Franklin) but quickly became a musical performance initiated by Djokovic and Franklin, with chair umpire Matthew Morrison (of the TV show "Glee") handing a microphone to the seemingly surprised Jepsen. During the number, the tennis court was filled with ball kids doing choreographed dance moves, a four-piece back-up band, a juggle, a marching band, Djokovic pushing a lawnmower as in the official video, and many other performers. Carly Rae Jepsen and Harvey Keitel performed "Call Me Maybe" alternating their own version of it during Comedy Central's "Night of Too Many Stars" autism benefit show on October 21, 2012. In 2013, she performed the song at grand launching of NET.


title: Call Me Maybe

text: A number of parody and lip dub videos have been released throughout the internet since the song's release. Big Time Rush, Ashley Tisdale, Justin Bieber, and Selena Gomez uploaded a parody video to YouTube on February 18, 2012; it instantly turned viral, having over 75 million views as of August 2019. Pop singer Katy Perry also released a viral video with her friends on April 19, 2012, while hosts and members of the E! TV series "Fashion Police" also released theirs on May 4, 2012. On May 23, 2012, a compilation from several fan videos was uploaded to Jepsen's Vevo page. The Harvard University baseball team uploaded a lip-sync video to the song on YouTube on May 6, 2012, which it had recorded on the way to a game over spring break. As of August 2019, it had been viewed over 19 million times. The Miami Dolphins Cheerleaders have also made a cover of the song that has garnered over 25 million views as of August 2019. On July 11, 2012, Crystal Palace F.C. released a cover version, in which the Crystal Palace cheerleaders squad, "the Crystals", sang and danced along to "Call Me Maybe". A promotional campaign to encourage the sale of season's tickets at the club, it was dubbed "Call Me Crystals".


title: Call Me Maybe

text: In July 2012, members of the United States Armed Forces stationed in Kandahar International Airport, Afghanistan had released another lip dub video with the idea to show troops in a more positive, light-hearted way. The "Baracksdubs" YouTube channel used Auto-Tune to produce a satire version from clips of Barack Obama. New York Mets infielder Justin Turner has also used the song as his at-bat music at home games. On July 3, 2012, Mabson Enterprises released a digital-only compilation on Bandcamp comprising 43 versions of the track remixed or covered including tracks by Dan Deacon, Ear Pwr, Poingly and Sean Carnage. On July 20, 2012, the cast of "Hollywood Heights", Cody Longo, Brittany Underwood, Carlos Ponce, Melissa Ordway, Jama Williamson, Meredith Salenger, among others, made a cover version of them lip singing and dancing along to the song on set of the show. On July 26, 2012, the United States Olympic swimming team posted a video of them lip syncing to the song at practice and on the way to London for the Olympics. On July 30, 2012, a mashup video featuring NASA videos of the Mars Science Laboratory was posted on YouTube, just a week before the Curiosity rover landed on Mars. The video was then updated after the landing and played for the Mars Curiosity Rover team at the Jet Propulsion Laboratory as the wake up video for Sol 18 on August 24, 2012. The cast of "The Big Bang Theory" made a flashmob of the song on October 23, 2012, during the live taping of an episode.


title: Call Me Maybe

text: A number of covers also emerged since the song's release. On March 24, 2012, Cimorelli performed a dance routine version of the song. The group returned in a sequel titled "Don't Call Me Baby", this time featuring MattyBRaps on May 9. On June 7, 2012, producer Chi Duly released "Call Me Calvin (Chi Duly Edit)", a mashup which replaced the original backing of "Call Me Maybe" with Calvin Harris' singles "I'm Not Alone", "Feel So Close", and "We Found Love".


title: Call Me Maybe

text: On July 10, 2012, "Sesame Street" released a parody of the song, called "Share it Maybe", which features "Cookie Monster-ified lyrics". A cover of the song released by Carly Rae Jepsen Tribute Team peaked at number 49 on the UK Singles Chart for one week and another version by Hit Masters spent the same amount of time on the chart but peaked 23 places lower, at number 72. American indie pop band Fun covered "Call Me Maybe" in an acoustic form at an in-studio session for Dutch radio 3FM. On May 8, 2012, folk artist Ben Howard covered the song for BBC Radio. Renditions from other notable people include James Franco and Colin Powell. On July 30, 2012, video game developer HeR Interactive, well known for the "Nancy Drew" computer games, added a new video parody of the song about Nancy Drew, titled "Call Me Nancy, Second Chance Me", a reference to the "Second Chance" feature in its games.


title: Call Me Maybe

text: On the fourth season of "Glee" premiere episode "The New Rachel", they covered "Call Me Maybe" as a way to decide who the "new Rachel" will be. During the Australian fourth season of "The X Factor", the finalists recorded and performed a cover of "Call Me Maybe" as a charity single in aid of Sony Foundation's You Can program. Girls Aloud covered "Call Me Maybe" live during their . Los Angeles comedy punk band Radioactive Chicken Heads recorded a punk rock version of the song in November 2012, also releasing a music video concurrently with their punk rock cover of Taylor Swifts "We Are Never Ever Getting Back Together". During the first episode of the eighth season of "America's Got Talent", aired on June 4, 2013, the 3 Penny Chorus and Orchestra directed by Arianne Abela did a cover of "Call Me Maybe", arranged by Colin Britt and Arianne Abela. "Weird Al" Yankovic briefly covered the song as part of his polka medley "NOW That's What I Call Polka!" for his 2014 album "Mandatory Fun". For the thirtieth anniversary of MathWorks in 2014, a group of employees created a flashmob-style parody version called "Call Me Nerdy". Baltimore rapper JPEGMafia released his own cover for the song as well. On September 25, 2020, a short for the Disney Channel show "Gravity Falls" was released. In that short, one of the main characters, Mabel, sings "Call Me Mabel", a parody of the song.


title: Kitchen sink realism

text: Kitchen sink realism (or kitchen sink drama) is a British cultural movement that developed in the late 1950s and early 1960s in theatre, art, novels, film and television plays, whose protagonists usually could be described as "angry young men" who were disillusioned with modern society. It used a style of social realism which depicted the domestic situations of working-class Britons, living in cramped rented accommodation and spending their off-hours drinking in grimy pubs, to explore controversial social and political issues ranging from abortion to homelessness. The harsh, realistic style contrasted sharply with the escapism of the previous generation's so-called "well-made plays".


title: Kitchen sink realism

text: The films, plays and novels employing this style are often set in poorer industrial areas in the North of England, and use the accents and slang heard in those regions. The film "It Always Rains on Sunday" (1947) is a precursor of the genre and the John Osborne play "Look Back in Anger" (1956) is thought of as the first of the genre. The gritty love-triangle of "Look Back in Anger", for example, takes place in a cramped, one-room flat in the English Midlands. Shelagh Delaney's 1958 play "A Taste of Honey" (which was made into a film of the same name in 1961) is about a teenage schoolgirl who has an affair with a black sailor, gets pregnant and then moves in with a gay male acquaintance; it raises issues such as class, ethnicity, gender and sexual orientation. The conventions of the genre have continued into the 2000s, finding expression in such television shows as "Coronation Street" and "EastEnders".


title: Kitchen sink realism

text: The term "Kitchen Sink School" was first used in the visual arts, where the art critic David Sylvester used it in 1954 to describe a group of painters who called themselves the Beaux Arts Quartet, and depicted social realist-type scenes of domestic life.


title: Kitchen sink realism

text: The cultural movement was rooted in the ideals of social realism, an artistic movement expressed in the visual and other realist arts which depicts working class activities. Many artists who subscribed to social realism were painters with socialist political views. While the movement has some commonalities with Socialist Realism, another style of realism which was the "official art" advocated by the governments of the Soviet Union and other Eastern Bloc countries, the two had several differences. While social realism is a broader type of art that realistically depicts subjects of social concern, Socialist realism is characterized by the glorified depiction of socialist values, such as the emancipation of the proletariat, in a realistic manner.


title: Kitchen sink realism

text: Unlike Socialist realism, social realism is not an official art produced by or under the supervision of the government. The leading characters are often 'anti-heroes' rather than part of a class to be admired, as in Socialist realism. Typically, protagonists in social realism are dissatisfied with their working class lives and the world, rather than being idealised workers who are part of a Socialist utopia in the process of creation. As such, social realism allows more space for the subjectivity of the author to be displayed.


title: Kitchen sink realism

text: Partly, social realism developed as a reaction against Romanticism, which promoted lofty concepts such as the "ineffable" beauty and truth of art and music and even turned them into spiritual ideals. As such, social realism focused on the "ugly realities of contemporary life and sympathized with working class people, particularly the poor." (The quotation is from George Shi, of the University of Fine Arts, Valencia).


title: Kitchen sink realism

text: Kitchen sink realism involves working class settings and accents, including accents from Northern England. The films and plays often explore taboo subjects such as adultery, pre-marital sex, abortion, and crime.


title: Kitchen sink realism

text: In the United Kingdom, the term "kitchen sink" derived from an expressionist painting by John Bratby that contained an image of a kitchen sink. Bratby did various kitchen and bathroom-themed paintings, including three paintings of toilets. Bratby's paintings of people often depicted the faces of his subjects as desperate and unsightly. Kitchen sink realism artists painted everyday objects, such as trash cans and beer bottles. The critic David Sylvester wrote an article in 1954 about trends in recent English art, calling his article "The Kitchen Sink" in reference to Bratby's picture. Sylvester argued that there was a new interest among young painters in domestic scenes, with stress on the banality of life. Other artists associated with the kitchen sink style include Derrick Greaves, Edward Middleditch and Jack Smith.


title: Kitchen sink realism

text: Before the 1950s, the United Kingdom's working class were often depicted stereotypically in Noël Coward's drawing room comedies and British films. Kitchen sink realism was seen as being in opposition to the "well-made play", the kind which theatre critic Kenneth Tynan once denounced as being set in "Loamshire", of dramatists like Terence Rattigan. "Well-made plays" were a dramatic genre from nineteenth-century theatre which found its early 20th-century codification in Britain in the form of William Archer's "Play-Making: A Manual of Craftmanship" (1912), and in the United States with George Pierce Baker's "Dramatic Technique" (1919). Kitchen sink works were created with the intention of changing all that. Their political views were initially labeled as radical, sometimes even anarchic.


title: Kitchen sink realism

text: John Osborne's play "Look Back in Anger" (1956) depicted young men in a way that is similar to the then-contemporary "Angry Young Men" movement of film and theatre directors. The "angry young men" were a group of mostly working and middle class British playwrights and novelists who became prominent in the 1950s. Following the success of the Osborne play, the label "angry young men" was later applied by British media to describe young writers who were characterised by a disillusionment with traditional British society. The hero of "Look Back In Anger" is a graduate, but he is working in a manual occupation. It dealt with social alienation, the claustrophobia and frustrations of a provincial life on low incomes.


title: Kitchen sink realism

text: The impact of this work inspired Arnold Wesker, Shelagh Delaney, and numerous others, to write plays of their own. The English Stage Company at the Royal Court Theatre, headed by George Devine and Theatre Workshop organised by Joan Littlewood were particularly prominent in bringing these plays to public attention. Critic John Heilpern wrote that "Look Back in Anger" expressed such "immensity of feeling and class hatred" that it altered the course of English theatre. The term "Angry theatre" was coined by critic John Russell Taylor.


title: Kitchen sink realism

text: This was all part of the British New Wave—a transposition of the concurrent "nouvelle vague" film movement in France, some of whose works, such as "The 400 Blows" of 1959, also emphasised the lives of the urban proletariat. British filmmakers such as Tony Richardson and Lindsay Anderson (see also Free Cinema) channelled their vitriolic anger into film making. Confrontational films such as "Saturday Night and Sunday Morning" (1960) and "A Taste of Honey" (1961) were noteworthy movies in the genre. "Saturday Night and Sunday Morning" is about a young machinist who spends his wages at weekends on drinking and having a good time, until his affair with a married woman leads to her getting pregnant and him being beaten by her husband's cousins to the point of hospitalisation. "A Taste of Honey" is about a 16-year old schoolgirl with an abusive, alcoholic mother. The schoolgirl starts a relationship with a black sailor and gets pregnant. After the sailor leaves on his ship, Jo moves in with a homosexual acquaintance who assumes the role of surrogate father. "A Taste of Honey" raises the issues of class, race, gender and sexual orientation.


title: Kitchen sink realism

text: Later, as many of these writers and directors diversified, kitchen sink realism was taken up by television directors who produced television plays. The single play was then a staple of the medium, and "Armchair Theatre" (1956–68), produced by the ITV contractor ABC, "The Wednesday Play" (1964–70) and "Play for Today" (1970–84), both BBC series, contained many works of this kind. Jeremy Sandford's television play "Cathy Come Home" (1966, directed by Ken Loach for "The Wednesday Play" slot) for instance, addressed the issue of homelessness.


title: Kitchen sink realism

text: The influence of kitchen sink realism has continued in the work of many more recent British directors, most notably Ken Loach (whose first directorial roles were in late 1960s kitchen sink dramas) and Mike Leigh. Other directors to continue working within the spirit of kitchen sink realism include Shane Meadows, Andrea Arnold, Clio Barnard, and Lynne Ramsay. The term "neo kitchen sink" has been used for films such as Leigh's 2004 "Vera Drake".


title: Ashton Sanders

text: Ashton Durrand Sanders (born October 24, 1995) is an American actor best known for his portrayal of teenage Chiron in the Academy Award-winning film "Moonlight" (2016).


title: Ashton Sanders

text: Sanders was born in Carson, California. He attended Grand Arts High School in Downtown Los Angeles, from which he graduated in 2013. He was studying towards a BFA at The Theatre School at DePaul University, before leaving after three years in 2016 to focus on his acting career.


title: Ashton Sanders

text: Sanders made his film debut in "The Retrieval", directed by Chris Eska. The film had its world premiere at South by Southwest on March 11, 2013. It was released in a limited release on April 2, 2014 by Variance Films.


title: Ashton Sanders

text: In 2015, Sanders had a small role in "Straight Outta Compton". In 2016, he appeared in an episode of Refinery29's web series "The Skinny".


title: Ashton Sanders

text: The same year, Sanders appeared in the drama film "Moonlight", directed by Barry Jenkins. The film had its world premiere at the Telluride Film Festival on September 2, 2016, and began a limited release on October 21, 2016 by A24. "Moonlight" received massive critical acclaim as well dozens of accolades, including the Golden Globe Award for Best Picture – Drama. The film also won three Academy Awards for Best Picture, Best Adapted Screenplay, and Best Supporting Actor for Mahershala Ali. Sanders' role in the film was praised by critics; Benjamin Lee of "The Guardian" called his performance "powerful".


title: Ashton Sanders

text: Sanders co-starred in "The Equalizer 2", a sequel to the hit action film "The Equalizer", opposite Denzel Washington. In 2019, Sanders starred in Rupert Wyatt's science fiction thriller film "Captive State", opposite John Goodman and Vera Farmiga. He also played the lead in HBO's adaptation of the novel "Native Son". In November 2020, he was set to star in "The Things They Carried", a Vietnam war movie featuring an ensemble cast.


title: Ashton Sanders

text: In September 2021, Sanders was cast as Bobby Brown in "I Wanna Dance with Somebody", a biopic feature on Whitney Houston.


title: President of Afghanistan

text: The president of the Islamic Republic of Afghanistan was constitutionally the head of state and head of government of the Islamic Republic of Afghanistan (2004–2021) and Commander-in-Chief of the Afghan Armed Forces.


title: President of Afghanistan

text: On 15 August 2021, as the Taliban took over Kabul, President Ashraf Ghani fled Afghanistan and took refuge in the United Arab Emirates. After Ghani fled, the Taliban occupied the Arg presidential palace.


title: President of Afghanistan

text: Article 62 of the 2004 Constitution of Afghanistan stated that a candidate for the office of President had to:


title: President of Afghanistan

text: The 2004 Constitution granted the president wide powers over military and legislative affairs, with a relatively weak national bicameral National Assembly, the House of the People (Wolesi Jirga) and the House of Elders (Meshrano Jirga). A president could only serve up to two five-year terms.


title: President of Afghanistan

text: Hamid Karzai began his first five-year term in 2004. After his second term ended in 2014, Ashraf Ghani was elected as the next Afghan president.


title: Volkan Oezdemir

text: Volkan Oezdemir (born 19 September 1989) is a Swiss professional mixed martial artist and former kickboxing practitioner. He currently competes in the Light heavyweight division in the Ultimate Fighting Championship (UFC). A professional competitor since 2010, Oezdemir formerly competed for Bellator. As a kickboxing practitioner, he competed for Superkombat Fighting Championship in their heavyweight division. As of December 6, 2022, he is #10 in the UFC light heavyweight rankings.


title: Volkan Oezdemir

text: Oezdemir was born in the French-speaking part of Switzerland. His father from Turkey is ethnically Kurdish and his mother is Swiss. He befriended Alistair Overeem on a visit to the Netherlands while training at the Golden Glory gym. Oezdemir later competed in amateur and professional kickboxing, as well as Brazilian Jiu-Jitsu, before transitioning to mixed martial arts.


title: Volkan Oezdemir

text: Oezdemir made his professional MMA debut in 2010, and compiled a record of 9–0 before being signed by Bellator.


title: Volkan Oezdemir

text: Oezdemir made his promotional debut at Bellator 105 on October 25, 2013, against Josh Lanier. He won the fight via first-round TKO.


title: Volkan Oezdemir

text: Oezdemir then dropped down to the Light Heavyweight division to face Kelly Anundson at Bellator 115 on April 4, 2014. He lost the fight via a neck crank submission in the second round.


title: Volkan Oezdemir

text: Oezdemir was signed by the UFC in 2017, and made his promotional debut as a short notice injury replacement against Ovince St. Preux on February 4, 2017, at UFC Fight Night 104. Oezdemir defeated St. Preux by split decision in the third fight of the main card.


title: Volkan Oezdemir

text: In his second fight for the promotion, Oezdemir faced Misha Cirkunov on May 28, 2017, at UFC Fight Night 109. He won the fight via knockout just 28 seconds into the first round.


title: Volkan Oezdemir

text: Oezdemir next faced third ranked Jimi Manuwa on July 29, 2017, at UFC 214. He won the fight via knockout in the fight's opening minute and subsequently won a "Performance of the Night" bonus.


title: Volkan Oezdemir

text: Oezdemir faced Daniel Cormier on January 20, 2018, at UFC 220 for the UFC Light Heavyweight Championship. He lost the fight via TKO in the second round.


title: Volkan Oezdemir

text: Oezdemir was expected to face Maurício Rua on May 12, 2018, at UFC Fight Night 129. However it was reported on April 13, 2018, that Oezdemir was pulled from the event due to alleged visa issues restricting his travel to Chile. The pairing was left intact and rescheduled for July 22, 2018, at UFC Fight Night 134. On July 2, 2018, it was reported that the Oezdemir would face Alexander Gustafsson instead on August 4, 2018, at UFC 227. However, on July 19, 2018, it was reported that Oezdemir was removed from the bout due to a broken nose.


title: Volkan Oezdemir

text: Oezdemir faced Anthony Smith on October 27, 2018, at UFC Fight Night 138. He lost the fight via a rear-naked choke submission in the third round.


title: Volkan Oezdemir

text: Oezdemir faced Dominick Reyes on March 16, 2019, at UFC Fight Night 147. He lost the fight via controversial split decision.


title: Volkan Oezdemir

text: Oezdemir was expected to face Ilir Latifi on June 1, 2019, at UFC Fight Night 153. On May 30, 2019, it was reported that Latifi was forced to pull out of the event due to back injury and the bout was cancelled. The pair was rebooked at UFC on ESPN 5 on August 3, 2019. In turn, due to Oezdemir's visa issues entering the United States, the bout was moved to UFC Fight Night 156. He won the fight via knockout in the second round. This win earned him the "Performance of the Night" award.


title: Volkan Oezdemir

text: Oezdemir faced Aleksandar Rakić on December 21, 2019, at UFC Fight Night 165. He won the fight via split decision.


title: Volkan Oezdemir

text: Oezdemir faced promotional newcomer Jiří Procházka on July 12, 2020, at UFC 251. He lost the fight via knockout in the second round.


title: Volkan Oezdemir

text: Oezdemir was expected to face Nikita Krylov on October 18, 2020, at UFC Fight Night 180. However, Oezdemir pulled out of the fight in early October citing a knee injury.


title: Volkan Oezdemir

text: Oezdemir was scheduled to face Magomed Ankalaev on September 4, 2021, at UFC Fight Night 191. However, the fight was rescheduled for UFC 267 in Abu Dhabi on October 30. He lost the bout via unanimous decison.


title: Volkan Oezdemir

text: Oezdemir faced Paul Craig on July 23, 2022, at UFC Fight Night 208. He won the bout by unanimous decision.


title: Volkan Oezdemir

text: Oezdemir faced Nikita Krylov on October 22, 2022 at UFC 280. He lost the bout via unanimous decision.


title: Volkan Oezdemir

text: Oezdemir also holds a record of 5–0 in professional kickboxing. He made his debut in Romania-based SUPERKOMBAT, the largest kickboxing promotion in Europe, in 2014.


title: Volkan Oezdemir

text: On 19 November 2017, Oezdemir was arrested for aggravated battery. His bail was reportedly set at $10,000. On 9 July 2018, he informed that the charges pressed against him were dropped.


Reverse transcription polymerase chain reaction (RT-PCR) is a laboratory technique combining reverse transcription of RNA into DNA (in this context called complementary DNA or cDNA) and amplification of specific DNA targets using polymerase chain reaction (PCR). It is primarily used to measure the amount of a specific RNA. This is achieved by monitoring the amplification reaction using fluorescence, a technique called real-time PCR or quantitative PCR (qPCR). Combined RT-PCR and qPCR are routinely used for analysis of gene expression and quantification of viral RNA in research and clinical settings.


title: Reverse transcription polymerase chain reaction

text: The close association between RT-PCR and qPCR has led to metonymic use of the term qPCR to mean RT-PCR. Such use may be confusing, as RT-PCR can be used without qPCR, for example to enable molecular cloning, sequencing or simple detection of RNA. Conversely, qPCR may be used without RT-PCR, for example to quantify the copy number of a specific piece of DNA.


text: The combined RT-PCR and qPCR technique has been described as quantitative RT-PCR or real-time RT-PCR (sometimes even called quantitative real-time RT-PCR), has been variously abbreviated as qRT-PCR, RT-qPCR, RRT-PCR, and rRT-PCR. In order to avoid confusion, the following abbreviations will be used consistently throughout this article:


text: Not all authors, especially earlier ones, use this convention and the reader should be cautious when following links. RT-PCR has been used to indicate both real-time PCR (qPCR) and reverse transcription PCR (RT-PCR).


text: Since its introduction in 1977, Northern blot has been used extensively for RNA quantification despite its shortcomings: (a) time-consuming technique, (b) requires a large quantity of RNA for detection, and (c) quantitatively inaccurate in the low abundance of RNA content. However, since PCR was invented by Kary Mullis in 1983, RT PCR has since displaced Northern blot as the method of choice for RNA detection and quantification.


text: RT-PCR has risen to become the benchmark technology for the detection and/or comparison of RNA levels for several reasons: (a) it does not require post PCR processing, (b) a wide range (>10-fold) of RNA abundance can be measured, and (c) it provides insight into both qualitative and quantitative data. Due to its simplicity, specificity and sensitivity, RT-PCR is used in a wide range of applications from experiments as simple as quantification of yeast cells in wine to more complex uses as diagnostic tools for detecting infectious agents such as the avian flu virus and SARS-CoV-2.


text: In RT-PCR, the RNA template is first converted into a complementary DNA (cDNA) using a reverse transcriptase (RT). The cDNA is then used as a template for exponential amplification using PCR. The use of RT-PCR for the detection of RNA transcript has revolutionized the study of gene expression in the following important ways:


text: The quantification of mRNA using RT-PCR can be achieved as either a one-step or a two-step reaction. The difference between the two approaches lies in the number of tubes used when performing the procedure. The two-step reaction requires that the reverse transcriptase reaction and PCR amplification be performed in separate tubes. The disadvantage of the two-step approach is susceptibility to contamination due to more frequent sample handling. On the other hand, the entire reaction from cDNA synthesis to PCR amplification occurs in a single tube in the one-step approach. The one-step approach is thought to minimize experimental variation by containing all of the enzymatic reactions in a single environment. It eliminates the steps of pipetting cDNA product, which is labor-intensive and prone to contamination, to PCR reaction. The further use of inhibitor-tolerant polymerases, polymerase enhancers with an optimized one-step RT-PCR condition, supports the reverse transcription of the RNA from unpurified or crude samples, such as whole blood and serum. However, the starting RNA templates are prone to degradation in the one-step approach, and the use of this approach is not recommended when repeated assays from the same sample is required. Additionally, the one-step approach is reported to be less accurate compared to the two-step approach. It is also the preferred method of analysis when using DNA binding dyes such as SYBR Green since the elimination of primer-dimers can be achieved through a simple change in the melting temperature. Nevertheless, the one-step approach is a relatively convenient solution for the rapid detection of target RNA directly in biosensing.


text: Quantification of RT-PCR products can largely be divided into two categories: end-point and real-time. The use of end-point RT-PCR is preferred for measuring gene expression changes in small number of samples, but the real-time RT-PCR has become the gold standard method for validating quantitative results obtained from array analyses or gene expression changes on a global scale.


text: The measurement approaches of end-point RT-PCR requires the detection of gene expression levels by the use of fluorescent dyes like ethidium bromide, P32 labeling of PCR products using phosphorimager, or by scintillation counting. End-point RT-PCR is commonly achieved using three different methods: relative, competitive and comparative.


text: The emergence of novel fluorescent DNA labeling techniques in the past few years has enabled the analysis and detection of PCR products in real-time and has consequently led to the widespread adoption of real-time RT-PCR for the analysis of gene expression. Not only is real-time RT-PCR now the method of choice for quantification of gene expression, it is also the preferred method of obtaining results from array analyses and gene expressions on a global scale. Currently, there are four different fluorescent DNA probes available for the real-time RT-PCR detection of PCR products: SYBR Green, TaqMan, molecular beacons, and scorpion probes. All of these probes allow the detection of PCR products by generating a fluorescent signal. While the SYBR Green dye emits its fluorescent signal simply by binding to the double-stranded DNA in solution, the TaqMan probes', molecular beacons' and scorpions' generation of fluorescence depend on Förster Resonance Energy Transfer (FRET) coupling of the dye molecule and a quencher moiety to the oligonucleotide substrates.


text: Two strategies are commonly employed to quantify the results obtained by real-time RT-PCR; the standard curve method and the comparative threshold method.


text: The exponential amplification via reverse transcription polymerase chain reaction provides for a highly sensitive technique in which a very low copy number of RNA molecules can be detected. RT-PCR is widely used in the diagnosis of genetic diseases and, semiquantitatively, in the determination of the abundance of specific different RNA molecules within a cell or tissue as a measure of gene expression.


text: RT-PCR is commonly used in research methods to measure gene expression. For example, Lin et al. used qRT-PCR to measure expression of Gal genes in yeast cells. First, Lin et al. engineered a mutation of a protein suspected to participate in the regulation of Gal genes. This mutation was hypothesized to selectively abolish Gal expression. To confirm this, gene expression levels of yeast cells containing this mutation were analyzed using qRT-PCR. The researchers were able to conclusively determine that the mutation of this regulatory protein reduced Gal expression. Northern blot analysis is used to study the RNA's gene expression further.


text: RT-PCR can also be very useful in the insertion of eukaryotic genes into prokaryotes. Because most eukaryotic genes contain introns, which are present in the genome but not in the mature mRNA, the cDNA generated from a RT-PCR reaction is the exact (without regard to the error-prone nature of reverse transcriptases) DNA sequence that would be directly translated into protein after transcription. When these genes are expressed in prokaryotic cells for the sake of protein production or purification, the RNA produced directly from transcription need not undergo splicing as the transcript contains only exons. (Prokaryotes, such as E. coli, lack the mRNA splicing mechanism of eukaryotes).


text: RT-PCR can be used to diagnose genetic disease such as Lesch–Nyhan syndrome. This genetic disease is caused by a malfunction in the HPRT1 gene, which clinically leads to the fatal uric acid urinary stone and symptoms similar to gout. Analyzing a pregnant mother and a fetus for mRNA expression levels of HPRT1 will reveal if the mother is a carrier and if the fetus will likely to develop Lesch–Nyhan syndrome.


text: Scientists are working on ways to use RT-PCR in cancer detection to help improve prognosis, and monitor response to therapy. Circulating tumor cells produce unique mRNA transcripts depending on the type of cancer. The goal is to determine which mRNA transcripts serve as the best biomarkers for a particular cancer cell type and then analyze its expression levels with RT-PCR.


text: RT-PCR is commonly used in studying the genomes of viruses whose genomes are composed of RNA, such as Influenzavirus A, retroviruses like HIV and SARS-CoV-2.


text: Despite its major advantages, RT-PCR is not without drawbacks. The exponential growth of the reverse transcribed complementary DNA (cDNA) during the multiple cycles of PCR produces inaccurate end point quantification due to the difficulty in maintaining linearity. In order to provide accurate detection and quantification of RNA content in a sample, qRT-PCR was developed using fluorescence-based modification to monitor the amplification products during each cycle of PCR. The extreme sensitivity of the technique can be a double edged sword since even the slightest DNA contamination can lead to undesirable results. A simple method for elimination of false positive results is to include anchors, or tags, to the 5' region of a gene specific primer. Additionally, planning and design of quantification studies can be technically challenging due to the existence of numerous sources of variation including template concentration and amplification efficiency. Spiking in a known quantity of RNA into a sample, adding a series of RNA dilutions generating a standard curve, and adding in a no template copy sample (no cDNA) may used as controls.


text: One-step RT-PCR subjects mRNA targets (up to 6 kb) to reverse transcription followed by PCR amplification in a single test tube. It is important to note that using intact, high quality RNA and a sequence-specific primer will produce the best results.


text: Once a one-step RT-PCR kit with a mix of reverse transcriptase, Taq DNA polymerase, and a proofreading polymerase is selected and all necessary materials and equipment are obtained a reaction mix is to be prepared. The reaction mix includes dNTPs, primers, template RNA, necessary enzymes, and a buffer solution. The reaction mix is added to a PCR tube for each reaction, followed by template RNA. The PCR tubes are then placed in a thermal cycler to begin cycling. In the first cycle, synthesis of cDNA occurs. The second cycle is the initial denaturation wherein reverse transcriptase is inactivated. The remaining 40-50 cycles are the amplification, which includes denaturation, annealing, and elongation. When amplification is complete, the RT-PCR products can be analyzed with gel electrophoresis.


text: Two-step RT-PCR, as the name implies, occurs in two steps. First the reverse transcription and then the PCR. This method is more sensitive than the one-step method. Kits are also useful for two-step RT-PCR. Just as for one-step PCR, use only intact, high quality RNA for the best results. The primer for two-step PCR does not have to be sequence specific.


text: First combine template RNA, primer, dNTP mix, and nuclease-free water in a PCR tube. Then, add an RNase inhibitor and reverse transcriptase to the PCR tube. Next, place the PCR tube into a thermal cycler for one cycle wherein annealing, extending, and inactivating of reverse transcriptase occurs. Finally, proceed directly to step two which is PCR or store product on ice until PCR can be performed.


text: Add master mix which contains buffer, dNTP mix, MgCl, Taq polymerase and nuclease-free water to each PCR tube. Then add the necessary primer to the tubes. Next, place the PCR tubes in a thermal cycler for 30 cycles of the amplification program. This includes: denaturation, annealing, and elongation. The products of RT-PCR can be analyzed with gel electrophoresis.


text: Quantitative RT-PCR assay is considered to be the gold standard for measuring the number of copies of specific cDNA targets in a sample but it is poorly standardized. As a result, while there are numerous publications utilizing the technique, many provide inadequate experimental detail and use unsuitable data analysis to draw inappropriate conclusions. Due to the inherent variability in the quality of any quantitative PCR data, not only do reviewers have a difficult time evaluating these manuscripts, but the studies also become impossible to replicate. Recognizing the need for the standardization of the reporting of experimental conditions, the Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE, pronounced mykee) guidelines have been published by an international consortium of academic scientists. The MIQE guidelines describe the minimum information necessary for evaluating quantitative PCR experiments that should be required for publication for encouraging better experimental practice and ensuring the relevance, accuracy, correct interpretation, and repeatability of quantitative PCR data.


text: Besides reporting guidelines, the MIQE stresses the need to standardize the nomenclature associated with quantitative PCR to avoid confusion; for example, the abbreviation "qPCR" should be used for quantitative real-time PCR, while "RT-qPCR" should be used for reverse transcription-qPCR, and genes used for normalisation should be referred to as "reference genes" instead of "housekeeping genes". It also proposes that commercially derived terms like "TaqMan probes" should not be used, but instead referred to as "hydrolysis probes". Additionally, it is proposed that quantification cycle (Cq) be used to describe the PCR cycle used for quantification instead of threshold cycle (Ct), crossing point (Cp), and takeoff point (TOP), which refer to the same value but were coined by different manufacturers of real-time instruments.


text: The guideline consists of the following elements: 1) experimental design, 2) sample, 3) nucleic acid extraction, 4) reverse transcription, 5) qPCR target information, 6) oligonucleotides, 7) protocol, 8) validation, and 9) data analysis. Specific items within each element carry a label of either E (essential) or D (desirable). Those labelled E are considered critical and indispensable while those labelled D are considered peripheral yet important for best-practices.


title: Foley catheter

text: In urology, a Foley catheter (named for Frederic Foley, who produced the original design in 1929) is a flexible tube that a clinician passes through the urethra and into the bladder to drain urine. It is the most common type of indwelling urinary catheter.


title: Foley catheter

text: The tube has two separated channels, or "lumens", running down its length. One lumen, open at both ends, drains urine into a collection bag. The other has a valve on the outside end and connects to a balloon at the inside tip. The balloon is inflated with sterile water when it lies inside the bladder to stop it from slipping out. Manufacturers usually produce Foley catheters using silicone or coated natural latex. Coatings include polytetrafluoroethylene, hydrogel, or a silicon elastomer – the different properties of these surface coatings determine whether the catheter is suitable for 28-day or 3-month indwelling duration.


title: Foley catheter

text: Foley catheters should be used only when indicated, as use increases the risk of catheter-associated urinary tract infection (UTI) and other adverse effects. While female sex is generally recognised as a risk factor for UTIs, the differences in biological sex are reduced or even diminished while carrying catheters.


title: Foley catheter

text: The name comes from the designer, Frederic Foley, a surgeon who worked in Boston, Massachusetts in the 1930s. His original design was adopted by C. R. Bard, Inc. of Murray Hill, New Jersey, who manufactured the first prototypes and named them in honor of the surgeon.


title: Foley catheter

text: The relative size of a Foley catheter is described using French units (F). Alternatively, the size of a 10 F catheter might be expressed as 10 Ch (Charriere units – named after a 19th century French scientific instrument maker, Joseph-Frédéric-Benoît Charrière). The most common sizes are 10 F to 28 F. 1 F is equivalent to 0.33 mm = .013" = 1/77" of diameter. Foley catheters are usually color coded by size with a solid color band at the external end of the balloon inflation tube, allowing for easy identification of the size. Note: Colors for French sizes 5, 6, 8, 10 may vary significantly if intended for pediatric patients. Color for French size 26 may also be pink instead of black.


title: Foley catheter

text: Indwelling urinary catheters are most commonly used to assist people who cannot urinate on their own. Indications for using a catheter include providing relief when there is urinary retention, monitoring urine output for critically ill persons, managing urination during surgery, and providing end-of-life care.


title: Foley catheter

text: A Foley catheter can also be used to ripen the cervix during induction of labor. When used for this purpose, the procedure is called "extra-amniotic saline infusion". In this procedure, the balloon is inserted behind the cervical wall and inflated, for example with 30-80 mL of saline. The remaining length of the catheter is pulled slightly taut and taped to the inside of the woman's leg. The inflated balloon applies pressure to the cervix as the baby's head would prior to labor, causing it to dilate. As the cervix dilates over time, the catheter is readjusted to again be slightly taut and retaped to maintain pressure. When the cervix has dilated sufficiently, the catheter drops out.


title: Foley catheter

text: They are also used in cases of severe epistaxis (nosebleed) to block blood from freely flowing down the nasal passage into the mouth.


title: Foley catheter

text: Indwelling urinary catheters should not be used to monitor stable people who are able to urinate or for the convenience of the patient or hospital staff. Urethral trauma is the only absolute contraindication to the placement of a urinary catheter. Examination findings such as blood at the urethral meatus, or a high riding prostate necessitate a retrograde urethrogram prior to insertion.


title: Foley catheter

text: In the United States, catheter-associated urinary tract infection is the most common type of hospital-acquired infection. While UTIs are generally more common among females, the risk factor associated to anatomy is reduced while carrying catheters, some studies even showing no significant differences between the sex. Indwelling catheters should be avoided when there are alternatives, and when patients and caregivers discuss alternatives to indwelling urinary catheters with their physicians and nurses then sometimes an alternative may be found. Physicians can reduce their use of indwelling urinary catheters when they follow evidence-based guidelines for usage, such as those published by the Centers for Disease Control and Prevention.


title: Foley catheter

text: All catheterised bladders become colonised with bacteria within 24 hours. This is not an infection and is very poorly understood by clinicians. Whilst the presence of a catheter does increase the incidence of bloodstream infections secondary to a urinary origin, there is a huge amount of unnecessary, and likely harmful, antimicrobial prescribing on the basis of detection of asymptomatic bacteriuria. The industry is moving to silver-coated catheters in an attempt to reduce the incidence of urinary tract infections, although there is limited evidence of efficacy. An additional problem is that Foley catheters tend to become coated over time with a biofilm that can obstruct the drainage. This increases the amount of stagnant urine left in the bladder, which further contributes to urinary tract infections. When a Foley catheter becomes clogged, it must be flushed or replaced. There is currently not enough adequate evidence to conclude whether washouts are beneficial or harmful.


title: The Finest Hours (2016 film)

text: The Finest Hours is a 2016 American action thriller film directed by Craig Gillespie and produced by Walt Disney Pictures. The screenplay, written by Eric Johnson, Scott Silver, and Paul Tamasy, is based on "The Finest Hours: The True Story of the U.S. Coast Guard's Most Daring Sea Rescue" by Michael J. Tougias and Casey Sherman.<ref name="Tougias/Sherman">Tougias, Michael J. & Casey Sherman: "The Finer Hour: The True Story of the U.S. Coast Guard's Most Daring Sea Rescue"</ref> The film stars Chris Pine, Casey Affleck, Ben Foster, Holliday Grainger, John Ortiz, and Eric Bana, and chronicles the historic 1952 United States Coast Guard rescue of the crew of , after the ship split apart during a nor'easter off the New England coast.<ref name="Barbo/Webster87-89">Barbo and Webster, pp 87-89</ref>


title: The Finest Hours (2016 film)

text: "The Finest Hours" was released in the Disney Digital 3D, RealD 3D, and IMAX 3D formats on January 29, 2016. The film received mixed reviews from critics, and was a box office flop, grossing just $52 million against its $70–80 million production budget.


title: The Finest Hours (2016 film)

text: Bernard "Bernie" Webber, a crewman at Coast Guard Station Chatham, Massachusetts, on Cape Cod, has fallen in love with a local girl, Miriam Pentinen. The two plan to marry on April 16, but in accordance with Coast Guard regulations, Bernie must seek permission from the station's commanding officer, Daniel Cluff, although it is usually just a formality. On the day he is due to ask permission, February 18, 1952, the oil tanker shears in half off the Chatham coast after getting caught in a nor'easter. With the majority of the station's crew already underway with the rescue of the similarly damaged , Bernie is dispatched to pilot motor lifeboat "CG 36500" to rescue the crew of "Pendleton". Andrew Fitzgerald, Ervin Maske, and Richard P. Livesey volunteer to join Bernie on the rescue mission.


title: The Finest Hours (2016 film)

text: Meanwhile, the "Pendleton"s engineer, Ray Sybert, as the surviving senior officer, organizes the surviving seamen to steer the sinking stern of the tanker onto a submerged reef, where it can lodge until rescuers arrive. Miriam learns that Bernie is leading the rescue effort and believes it to be a suicide mission. Few people in Chatham trust Cluff, believing him to be incapable of doing his job because he is not from the area. Miriam drives to the station, demanding that Cluff call Bernie back. Cluff refuses, and brusquely orders Miriam out.


title: The Finest Hours (2016 film)

text: Between Chatham Harbor and the open sea lies a bar, a series of shoals that are very dangerous even in good weather. Bernie must time bursts of his engine to ride each approaching wave before it breaks as he pilots "CG 36500" across the bar. Although he makes it over the bar, he loses his compass.


title: The Finest Hours (2016 film)

text: Bernie steers "CG 36500" to the stricken tanker. Although his boat's designated capacity is only 12 people, Bernie manages to rescue 32 crewmen. The stern of "Pendleton" begins sinking more rapidly during the rescue and goes down shortly after the last crewman comes aboard Bernie's boat. Relying on his knowledge of the coast and prevailing winds in place of his compass, Bernie steers "CG 36500" toward home—a task made more difficult as Chatham loses power. Miriam and the other townspeople drive their cars to the pier and turn on their headlights to guide Bernie in.


title: The Finest Hours (2016 film)

text: The end of the film shows photographs from the event that briefly document the aftermath of the rescue. Two months later, Bernie and Miriam marry; they stay together for 58 years until Bernie's death in 2009. Bernie Webber and his crew receive the Gold Lifesaving Medal.


title: The Finest Hours (2016 film)

text: Walt Disney Pictures acquired the screen rights to Michael Tougias' 2009 book, "The Finest Hours: The True Story of a Heroic Sea Rescue" in August 2011"." Paul Tamasy and Eric Johnson wrote the script based on the book and interviews they conducted with survivors. In May 2013, Robert Schwentke was hired to direct the film. However, Schwentke left the project to direct "", and was replaced with Craig Gillespie in April 2014. Casting was done from April through October 2014.


title: The Finest Hours (2016 film)

text: Principal photography began on September 8, 2014, in Quincy, Massachusetts. On October 27, the film was being shot at Fore River Shipyard in Quincy aboard . They were also set to film at various South Shore locations and then move to Chatham, Massachusetts, in December. In early December, filming was taking place in the town of Marshfield. Affleck was seen playing piano at Symphony Hall in Boston on December 12, during the Chatham shoot, and expressed to the "Boston Globe" that his experience shooting the film was "one of [his] best". Production designer Michael Corenblith reproduced the interior of "Pendleton". Post-production lasted a year, with the film requiring nearly 1,000 visual effects shots. Moving Picture Company (MPC) was responsible for creating the majority of those shots.


title: The Finest Hours (2016 film)

text: Walt Disney Studios Motion Pictures originally set "The Finest Hours" for release on April 15, 2016, and then October 9, 2015, until announcing a final release date of January 29, 2016. The first trailer for the film was released on July 8, 2015. A second trailer was released on November 11, 2015. "The Finest Hours" opened the Coronado Island Film Festival on January 15, 2016. The film held its world premiere at the TCL Chinese Theatre in Hollywood, California, on January 25, 2016. Walt Disney Studios Home Entertainment released the film on Blu-ray, DVD, and digital download on May 24, 2016.


title: The Finest Hours (2016 film)

text: "The Finest Hours" grossed $27.6 million in North America and $24.5 million in other territories for a worldwide total of $52.1 million.


title: The Finest Hours (2016 film)

text: The film was released in North America on January 29, 2016, alongside "Kung Fu Panda 3", "Fifty Shades of Black", and "Jane Got a Gun". The film was projected to gross $10–13 million from 3,143 theaters in its opening weekend. The film grossed $375,000 from its Thursday night previews and $3.3 million on its first day. It went on to gross $10.3 million in its opening weekend, finishing 4th at the box office.


title: The Finest Hours (2016 film)

text: On Rotten Tomatoes, the film has an approval rating of 64% based on 195 reviews, with an average rating of 6/10. The site's consensus states, "Old-fashioned to a fault, "The Finest Hours" will satisfy those seeking a traditional rescue drama – but may leave more adventurous viewers wanting more." On Metacritic, the film has a score of 58 out of 100, based on 39 critics, indicating "mixed or average reviews". Audiences polled by CinemaScore gave the film an average grade of "A−" on an A+ to F scale.


title: The Finest Hours (2016 film)

text: Conducted by Carter Burwell. Performed by the Hollywood Studio Symphony. Portions of Carter Burwell's score were replaced with music composed by Philip Klein, who had served as arranger on Burwell's score. Burwell chose to include two of Klein's tracks on the album. The album also includes five tracks that Burwell recorded, but which were replaced in the finished film.


title: Sergeant Stubby

text: Sergeant Stubby (1916 – March 16, 1926) was a dog and the unofficial mascot of the 102nd Infantry Regiment (United States) and was assigned to the 26th (Yankee) Division in World War I. He served for 18 months and participated in 17 battles on the Western Front. He saved his regiment from surprise mustard gas attacks, found and comforted the wounded, and allegedly once caught a German soldier by the seat of his pants, holding him there until American soldiers found him. His actions were well-documented in contemporary American newspapers.


title: Sergeant Stubby

text: Stubby has been called the most decorated war dog of the Great War and the only dog to be nominated and promoted to sergeant through combat. Stubby's remains are in the Smithsonian Institution.


title: Sergeant Stubby

text: Stubby was described in contemporaneous news items as a Boston Terrier or "American bull terrier" mutt. Describing him as a dog of "uncertain breed," Ann Bausum wrote that: "The brindle-patterned pup probably owed at least some of his parentage to the evolving family of Boston Terriers, a breed so new that even its name was in flux: Boston Round Heads, American... and Boston Bull Terriers." Stubby was found wandering the grounds of the Yale University campus in New Haven, Connecticut in July 1917, while members of the 102nd Infantry were training. He hung around as the men drilled and one soldier in particular, Corporal James Robert Conroy (1892-1987), developed a fondness for him. When it came time for the outfit to ship out, Conroy hid Stubby on board the troop ship. As they were getting off the ship in France, he hid Stubby under his overcoat without detection. Upon discovery by Conroy's commanding officer, Stubby saluted him as he had been trained to in camp, and the commanding officer allowed the dog to stay on board.


title: Sergeant Stubby

text: Stubby served with the 102nd Infantry Regiment in the trenches in France for 18 months and participated in four offensives and 17 battles. He entered combat on February 5, 1918, at Chemin des Dames, north of Soissons, and was under constant fire, day and night for over a month. In April 1918, during a raid to take Seicheprey, Stubby was wounded in the foreleg by retreating Germans throwing hand grenades. He was sent to the rear for convalescence and, as he had done on the front, improved morale. When he recovered from his wounds, Stubby returned to the trenches.


title: Sergeant Stubby

text: In his first year of battle, Stubby was injured by mustard gas. After he recovered, he returned with a specially designed gas mask to protect him. He thus learned to warn his unit of mustard gas attacks, locate wounded soldiers in no man's land, and—since he could hear the whine of incoming artillery shells before humans—became very adept at alerting his unit when to duck for cover. He was solely responsible for capturing a German spy in the Argonne, leading to their unit's commander nominating Stubby for the rank of sergeant. Following the retaking of Château-Thierry by the U.S., women of the town made Stubby a chamois coat upon which his many medals were pinned. He was later injured again, in the chest and leg by a grenade. He ultimately had two wound stripes. At the end of the war, Robert Conroy smuggled Stubby home.


title: Sergeant Stubby

text: After returning home, Stubby became a celebrity and marched in, and normally led, many parades across the country. He met Presidents Woodrow Wilson, Calvin Coolidge, and Warren G. Harding. He also appeared on vaudeville stages owned by Sylvester Z. Poli and was awarded lifetime memberships to the American Legion and the YMCA.


title: Sergeant Stubby

text: In 1921, General of the Armies John J. Pershing presented a gold medal from the Humane Education Society to Stubby, the subject of a famous photograph and other artistic media. During that same year, he attended Georgetown University Law Center along with Conroy, and became the Georgetown Hoyas' team mascot. Given a football at halftime, he would nudge it around the field, to the amusement of the fans. While still a student at Georgetown, Conroy was also employed as a special agent of the Bureau of Investigation, precursor to the FBI.


title: Sergeant Stubby

text: Stubby died in his sleep in March 1926. After his death he was preserved via taxidermy and his cremains were sealed inside of the mount. Conroy later presented Stubby to the Smithsonian in 1956. The taxidermy mount of the dog is part of the permanent collection at the Smithsonian National Museum of American History and is currently on display in their “Price of Freedom: Americans at War” exhibit.


title: Sergeant Stubby

text: Stubby received an obituary in the "New York Times" following his death in 1926. The obituary was half a page, much longer than the obituaries of many notable people of that time period.


title: Sergeant Stubby

text: He was also the subject of a portrait by "Capitol artist" Charles Ayer Whipple. He was featured in the "Brave Beasts" exhibit at the Legermuseum in Delft, The Netherlands from 2008 to 2009. During a ceremony held on Armistice Day in 2006, a brick was placed in the Walk of Honor at the Liberty Memorial in Kansas City to commemorate Sergeant Stubby.


title: Sergeant Stubby

text: Stubby was the subject of at least four books. In 2014, BBC Schools WWI series used Stubby as a Famous Figure to help teach children about the war, along with creating an animated comic strip to illustrate his life.


title: Sergeant Stubby

text: The descendants of Robert Conroy dedicated a life-size bronze statue of Stubby named "Stubby Salutes," by Susan Bahary, in the Connecticut Trees of Honor Memorial at Veteran's Memorial Park in Middletown, Connecticut, in May 2018. The statue pays tribute to fallen Connecticut veterans, where both Stubby and Robert Conroy are from.


title: Sergeant Stubby

text: "" is an animated feature-length film based on the life and times of Stubby. Theatrically released on April 13, 2018, the film features the voices of Logan Lerman, Helena Bonham Carter, and Gérard Depardieu with music by Academy Award nominee Patrick Doyle. The animation is made by the studio Mikros Image and produced by Irish-American studio Fun Academy Media Group.


title: Sergeant Stubby

text: The film received high marks from film critics and was officially endorsed by several high-profile institutions, including the Humane Society of the United States, the Armed Services YMCA, the Westminster Kennel Club, and the United States World War One Centennial Commission. Unfortunately, the film's nationwide release coincided with studio tent-poles "" and "Rampage", as well as the expansion of Wes Anderson's critically acclaimed, animated dog movie "Isle of Dogs."


title: Sergeant Stubby

text: The film received generally positive reviews and numerous awards including the Parents' Choice Foundation Gold Award and The Dove Foundation's All Ages Seal of Approval, despite the film not containing any explicit faith-based messaging.


title: Sergeant Stubby

text: Despite the initial theatrical setback, "Sgt. Stubby" has been released in over two dozen countries and picked up festival awards in Australia, France, Spain, and the United Kingdom. In December 2018, "Sgt. Stubby" was acquired for home media distribution by Paramount Pictures.


title: Sergeant Stubby

text: In November 2019, Fun Academy announced a new subscription-based fan club, The Stubby Squad, which offers members-only video programming, downloadable activities, and a crowdfunding element to help develop future Stubby projects. The website also offers a free web comic for non-members, "Stubby & Friends", and details regarding their plans to tell the rest of Stubby's life – including his time in vaudeville and accompanying Conroy on missions as a G-man – as well as an animated television series serving as a prequel to his adoption by Conroy.


title: Sergeant Stubby

text: The series was announced to be developed by writers Scott Christian Sava ("Animal Crackers", "The Dreamland Chronicles"), Audry Taylor ("Pet Robots"), and David Wise ("Teenage Mutant Ninja Turtles, "). Wise passed away months after the announcement.


title: Cytochrome P450

text: Cytochromes P450 (CYPs) are a superfamily of enzymes containing heme as a cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compounds, as well as for hormone synthesis and breakdown. In 1963, Estabrook, Cooper, and Rosenthal described the role of CYP as a catalyst in steroid hormone synthesis and drug metabolism. In plants, these proteins are important for the biosynthesis of defensive compounds, fatty acids, and hormones.


title: Cytochrome P450

text: CYP enzymes have been identified in all kingdoms of life: animals, plants, fungi, protists, bacteria, and archaea, as well as in viruses. However, they are not omnipresent; for example, they have not been found in "Escherichia coli". , more than 300,000 distinct CYP proteins are known.


title: Cytochrome P450

text: CYPs are, in general, the terminal oxidase enzymes in electron transfer chains, broadly categorized as P450-containing systems. The term "P450" is derived from the spectrophotometric peak at the wavelength of the absorption maximum of the enzyme (450 nm) when it is in the reduced state and complexed with carbon monoxide. Most CYPs require a protein partner to deliver one or more electrons to reduce the iron (and eventually molecular oxygen).


title: Cytochrome P450

text: Genes encoding CYP enzymes, and the enzymes themselves, are designated with the root symbol CYP for the superfamily, followed by a number indicating the gene family, a capital letter indicating the subfamily, and another numeral for the individual gene. The convention is to "italicise" the name when referring to the gene. For example, "CYP2E1" is the gene that encodes the enzyme CYP2E1—one of the enzymes involved in paracetamol (acetaminophen) metabolism. The CYP nomenclature is the official naming convention, although occasionally CYP450 or CYP is used synonymously. However, some gene or enzyme names for CYPs may differ from this nomenclature, denoting the catalytic activity and the name of the compound used as substrate. Examples include CYP5A1, thromboxane A synthase, abbreviated to TBXAS1 (ThromBoXane A Synthase 1), and CYP51A1, lanosterol 14-α-demethylase, sometimes unofficially abbreviated to LDM according to its substrate (Lanosterol) and activity (DeMethylation).


title: Cytochrome P450

text: The current nomenclature guidelines suggest that members of new CYP families share at least 40% amino-acid identity, while members of subfamilies must share at least 55% amino-acid identity. Nomenclature committees assign and track both base gene names (Cytochrome P450 Homepage ) and allele names (CYP Allele Nomenclature Committee).


title: Cytochrome P450

text: The most common reaction catalyzed by cytochromes P450 is a monooxygenase reaction, e.g., insertion of one atom of oxygen into the aliphatic position of an organic substrate (RH), while the other oxygen atom is reduced to water:


title: Cytochrome P450

text: The active site of cytochrome P450 contains a heme-iron center. The iron is tethered to the protein via a cysteine thiolate ligand. This cysteine and several flanking residues are highly conserved in known CYPs, and have the formal PROSITE signature consensus pattern [FW] - [SGNH] - x - [GD] - {F} - [RKHPT] - {P} - C - [LIVMFAP] - [GAD]. Because of the vast variety of reactions catalyzed by CYPs, the activities and properties of the many CYPs differ in many aspects. In general, the P450 catalytic cycle proceeds as follows:


title: Cytochrome P450

text: Binding of substrate is reflected in the spectral properties of the enzyme, with an increase in absorbance at 390 nm and a decrease at 420 nm. This can be measured by difference spectroscopies and is referred to as the "type I" difference spectrum (see inset graph in figure). Some substrates cause an opposite change in spectral properties, a "reverse type I" spectrum, by processes that are as yet unclear. Inhibitors and certain substrates that bind directly to the heme iron give rise to the type II difference spectrum, with a maximum at 430 nm and a minimum at 390 nm (see inset graph in figure). If no reducing equivalents are available, this complex may remain stable, allowing the degree of binding to be determined from absorbance measurements "in vitro"


title: Cytochrome P450

text: C: If carbon monoxide (CO) binds to reduced P450, the catalytic cycle is interrupted. This reaction yields the classic CO difference spectrum with a maximum at 450 nm. However, the interruptive and inhibitory effects of CO varies upon different CYPs such that the CYP3A family is relatively less affected.


title: Cytochrome P450

text: Human CYPs are primarily membrane-associated proteins located either in the inner membrane of mitochondria or in the endoplasmic reticulum of cells. CYPs metabolize thousands of endogenous and exogenous chemicals. Some CYPs metabolize only one (or a very few) substrates, such as "CYP19" (aromatase), while others may metabolize multiple substrates. Both of these characteristics account for their central importance in medicine. Cytochrome P450 enzymes are present in most tissues of the body, and play important roles in hormone synthesis and breakdown (including estrogen and testosterone synthesis and metabolism), cholesterol synthesis, and vitamin D metabolism. Cytochrome P450 enzymes also function to metabolize potentially toxic compounds, including drugs and products of endogenous metabolism such as bilirubin, principally in the liver.


title: Cytochrome P450

text: The Human Genome Project has identified 57 human genes coding for the various cytochrome P450 enzymes.


title: Cytochrome P450

text: CYPs are the major enzymes involved in drug metabolism, accounting for about 75% of the total metabolism. Most drugs undergo deactivation by CYPs, either directly or by facilitated excretion from the body. Also, many substances are bioactivated by CYPs to form their active compounds like the antiplatelet drug clopidogrel and the opiate codeine.


title: Cytochrome P450

text: Many drugs may increase or decrease the activity of various CYP isozymes either by inducing the biosynthesis of an isozyme (enzyme induction) or by directly inhibiting the activity of the CYP (enzyme inhibition). A classical example includes anti-epileptic drugs, such as Phenytoin, which induces CYP1A2, CYP2C9, CYP2C19, and CYP3A4.


title: Cytochrome P450

text: Effects on CYP isozyme activity are a major source of adverse drug interactions, since changes in CYP enzyme activity may affect the metabolism and clearance of various drugs. For example, if one drug inhibits the CYP-mediated metabolism of another drug, the second drug may accumulate within the body to toxic levels. Hence, these drug interactions may necessitate dosage adjustments or choosing drugs that do not interact with the CYP system. Such drug interactions are especially important to consider when using drugs of vital importance to the patient, drugs with significant side-effects, or drugs with a narrow therapeutic index, but any drug may be subject to an altered plasma concentration due to altered drug metabolism.


title: Cytochrome P450

text: Many substrates for CYP3A4 are drugs with a narrow therapeutic index, such as amiodarone or carbamazepine. Because these drugs are metabolized by CYP3A4, the mean plasma levels of these drugs may increase because of enzyme inhibition or decrease because of enzyme induction.


title: Cytochrome P450

text: Naturally occurring compounds may also induce or inhibit CYP activity. For example, bioactive compounds found in grapefruit juice and some other fruit juices, including bergamottin, dihydroxybergamottin, and paradicin-A, have been found to inhibit CYP3A4-mediated metabolism of certain medications, leading to increased bioavailability and, thus, the strong possibility of overdosing. Because of this risk, avoiding grapefruit juice and fresh grapefruits entirely while on drugs is usually advised.


title: Cytochrome P450

text: A subset of cytochrome P450 enzymes play important roles in the synthesis of steroid hormones (steroidogenesis) by the adrenals, gonads, and peripheral tissue:


title: Cytochrome P450

text: Certain cytochrome P450 enzymes are critical in metabolizing polyunsaturated fatty acids (PUFAs) to biologically active, intercellular cell signaling molecules (eicosanoids) and/or metabolize biologically active metabolites of the PUFA to less active or inactive products. These CYPs possess cytochrome P450 omega hydroxylase and/or epoxygenase enzyme activity.


title: Cytochrome P450

text: Humans have 57 genes and more than 59 pseudogenes divided among 18 families of cytochrome P450 genes and 43 subfamilies. This is a summary of the genes and of the proteins they encode. See the homepage of the cytochrome P450 Nomenclature Committee for detailed information.


title: Cytochrome P450

text: Animals often have more CYP genes than do humans. Reported numbers range from 35 genes in the sponge "Amphimedon queenslandica" to 235 genes in the cephalochordate "Branchiostoma floridae". Mice have genes for 101 CYPs, and sea urchins have even more (perhaps as many as 120 genes).


title: Cytochrome P450

text: Most CYP enzymes are presumed to have monooxygenase activity, as is the case for most mammalian CYPs that have been investigated (except for, e.g., CYP19 and CYP5). Gene and genome sequencing is far outpacing biochemical characterization of enzymatic function, though many genes with close homology to CYPs with known function have been found, giving clues to their functionality.


title: Cytochrome P450

text: The classes of CYPs most often investigated in non-human animals are those either involved in development (e.g., retinoic acid or hormone metabolism) or involved in the metabolism of toxic compounds (such as heterocyclic amines or polyaromatic hydrocarbons). Often there are differences in gene regulation or enzyme function of CYPs in related animals that explain observed differences in susceptibility to toxic compounds (ex. canines' inability to metabolize xanthines such as caffeine). Some drugs undergo metabolism in both species via different enzymes, resulting in different metabolites, while other drugs are metabolized in one species but excreted unchanged in another species. For this reason, one species's reaction to a substance is not a reliable indication of the substance's effects in humans. A species of Sonoran Desert Drosophila that uses an upregulated expression of the CYP28A1 gene for detoxification of cacti rot is "Drosophila mettleri". Flies of this species have adapted an upregulation of this gene due to exposure of high levels of alkaloids in host plants.


title: Cytochrome P450

text: CYPs have been extensively examined in mice, rats, dogs, and less so in zebrafish, in order to facilitate use of these model organisms in drug discovery and toxicology. Recently CYPs have also been discovered in avian species, in particular turkeys, that may turn out to be a useful model for cancer research in humans. CYP1A5 and CYP3A37 in turkeys were found to be very similar to the human CYP1A2 and CYP3A4 respectively, in terms of their kinetic properties as well as in the metabolism of aflatoxin B1.


title: Cytochrome P450

text: CYPs have also been heavily studied in insects, often to understand pesticide resistance. For example, CYP6G1 is linked to insecticide resistance in DDT-resistant "Drosophila melanogaster" and CYP6M2 in the mosquito malaria vector "Anopheles gambiae" is capable of directly metabolizing pyrethroids.


title: Cytochrome P450

text: Microbial cytochromes P450 are often soluble enzymes and are involved in diverse metabolic processes. In bacteria the distribution of P450s is very variable with many bacteria having no identified P450s (e.g. "E.coli"). Some bacteria, predominantly actinomycetes, have numerous P450s (e.g.,). Those so far identified are generally involved in either biotransformation of xenobiotic compounds (e.g. CYP105A1 from "Streptomyces griseolus" metabolizes sulfonylurea herbicides to less toxic derivatives,) or are part of specialised metabolite biosynthetic pathways (e.g. CYP170B1 catalyses production of the sesquiterpenoid albaflavenone in "Streptomyces albus"). Although no P450 has yet been shown to be essential in a microbe, the CYP105 family is highly conserved with a representative in every streptomycete genome sequenced so far. Due to the solubility of bacterial P450 enzymes, they are generally regarded as easier to work with than the predominantly membrane bound eukaryotic P450s. This, combined with the remarkable chemistry they catalyse, has led to many studies using the heterologously expressed proteins in vitro. Few studies have investigated what P450s do in vivo, what the natural substrate(s) are and how P450s contribute to survival of the bacteria in the natural environment.Three examples that have contributed significantly to structural and mechanistic studies are listed here, but many different families exist.


title: Cytochrome P450

text: The commonly used azole class antifungal drugs work by inhibition of the fungal cytochrome P450 14α-demethylase. This interrupts the conversion of lanosterol to ergosterol, a component of the fungal cell membrane. (This is useful only because humans' P450 have a different sensitivity; this is how this class of antifungals work.)


title: Cytochrome P450

text: Significant research is ongoing into fungal P450s, as a number of fungi are pathogenic to humans (such as Candida yeast and Aspergillus) and to plants.


title: Cytochrome P450

text: Cytochromes P450 are involved in a variety of processes of plant growth, development, and defense. It is estimated that CYP P450 genes make up approximately 1% of the plant genome. These enzymes lead to various fatty acid conjugates, plant hormones, secondary metabolites, lignins, and a variety of defensive compounds.


title: Cytochrome P450

text: Cytochrome P450s play an important role in plant defense– involvement in phytoalexin biosynthesis, hormone metabolism, and biosynthesis of diverse secondary metabolites. The expression of cytochrome p450 genes is regulated in response to environmental stresses indicative of a critical role in plant defense mechanisms.


title: Cytochrome P450

text: Phytoalexins have shown to be important in plant defense mechanisms as they are antimicrobial compounds produced by plants in response to plant pathogens. Phytoalexins are not pathogen-specific, but rather plant-specific; each plant has its own unique set of phytoalexins. However, they can still attack a wide range of different pathogens. Arabidopsis is a plant closely related to cabbage and mustard and produces the phytoalexin camalexin. Camalexin originates from tryptophan and its biosynthesis involves five cytochrome P450 enzymes. The five cytochrome P450 enzymes include CYP79B2, CYP79B3, CYP71A12, CYP71A13, and CYP71B15. The first step of camalexin biosynthesis produces indole-3-acetaldoxime (IAOx) from tryptophan and is catalyzed by either CYP79B2 or CYP79B3. IAOx is then immediately converted to indole-3-acetonitrile (IAN) and is controlled by either CYP71A13 or its homolog CYP71A12. The last two steps of the biosynthesis pathway of camalexin are catalyzed by CYP71B15. In these steps, indole-3-carboxylic acid (DHCA) is formed from cysteine-indole-3-acetonitrile (Cys(IAN)) followed by the biosynthesis of camalexin. There are some intermediate steps within the pathway that remain unclear, but it is well understood that cytochrome P450 is pivotal in camalexin biosynthesis and that this phytoalexin plays a major role in plant defense mechanisms.


title: Cytochrome P450

text: Cytochrome P450s are largely responsible for the synthesis of the jasmonic acid (JA), a common hormonal defenses against abiotic and biotic stresses for plant cells. For example, a P450, CYP74A is involved in the dehydration reaction to produce an insatiable allene oxide from hydroperoxide. JA chemical reactions are critical in the presence of biotic stresses that can be caused by plant wounding, specifically shown in the plant, Arabidopsis. As a prohormone, jasmonic acid must be converted to the JA-isoleucine (JA-Ile) conjugate by JAR1 catalysation in order to be considered activated. Then, JA-Ile synthesis leads to the assembly of the co-receptor complex compo`sed of COI1 and several JAZ proteins. Under low JA-Ile conditions, the JAZ protein components act as transcriptional repressors to suppress downstream JA genes. However, under adequate JA-Ile conditions, the JAZ proteins are ubiquitinated and undergo degradation through the 26S proteasome, resulting in functional downstream effects. Furthermore, several CYP94s (CYP94C1 and CYP94B3) are related to JA-Ile turnover and show that JA-Ile oxidation status impacts plant signaling in a catabolic manner. Cytochrome P450 hormonal regulation in response to extracellular and intracellular stresses is critical for proper plant defense response. This has been proven through thorough analysis of various CYP P450s in jasmonic acid and phytoalexin pathways.


title: Cytochrome P450

text: Cytochrome P450 aromatic O-demethylase, which is made of two distinct promiscuous parts: a cytochrome P450 protein (GcoA) and three domain reductase, is significant for its ability to convert Lignin, the aromatic biopolymer common in plant cell walls, into renewable carbon chains in a catabolic set of reactions. In short, it is a facilitator of a critical step in Lignin conversion.


title: Cytochrome P450

text: The remarkable reactivity and substrate promiscuity of P450s have long attracted the attention of chemists. Recent progress towards realizing the potential of using P450s towards difficult oxidations have included: (i) eliminating the need for natural co-factors by replacing them with inexpensive peroxide containing molecules, (ii) exploring the compatibility of P450s with organic solvents, and (iii) the use of small, non-chiral auxiliaries to predictably direct P450 oxidation.


title: Cytochrome P450

text: oxidize uroporphyrinogen to uroporphyrin (CYP1A2) in heme metabolism, but they may have additional undiscovered endogenous substrates.


title: Cytochrome P450

text: are inducible by some polycyclic hydrocarbons, some of which are found in cigarette smoke and charred food.


title: Cytochrome P450

text: High levels of CYP1A2 have been linked to an increased risk of colon cancer. Since the 1A2 enzyme can be induced by cigarette smoking, this links smoking with colon cancer.


title: Mérida, Yucatán

text: Mérida () is the capital of the Mexican state of Yucatán, and the largest city in southeastern Mexico. The city is also the seat of the eponymous Municipality. It is located in the northwest corner of the Yucatán Peninsula, about 35 km (22 mi) inland from the coast of the Gulf of Mexico. In 2020 it had a population of 921,770 while its metropolitan area, which also includes the cities of Kanasín and Umán, had a population of 1,316,090.


title: Mérida, Yucatán

text: The city's rich cultural heritage is a product of the syncretism of the Maya and Spanish cultures during the colonial era. It was the first city to be ever named American Capital of Culture and is the only city that has received the title twice. The Cathedral of Mérida, Yucatán was built in the late 16th century with stones from nearby Mayan ruins and is known to be the oldest cathedral in the mainland Americas. In addition, the city has the third largest old town district on the continent. In 2007, the city was visited by former U.S. President George W. Bush to meet with then-president of Mexico Felipe Calderón for the historic creation of the Mérida Initiative.


title: Mérida, Yucatán

text: Mérida is often considered the safest city of Mexico and one of the safest cities in the Americas. In 2019 it hosted the 17th World Summit of Nobel Peace Laureates, receiving more than 30 of them. It is a City of Gastronomy as part of the UNESCO's Creative Cities Network. The UN-Habitat's City Prosperity Index recognized Mérida as the best city to live in Mexico for its high quality of life. The city was certified as an International Safe Community by the Karolinska Institute of Sweden for its high level of public security. Forbes magazine has ranked Mérida three different times as one of the three best cities in Mexico to live, invest and do business.


title: Mérida, Yucatán

text: There were three Spanish conquistadors named "Francisco de Montejo": Francisco de Montejo "el Adelantado" ("The Lieutenant", the eldest); Francisco de Montejo y León "el Mozo" ("The Boy", his son); and Francisco de Montejo "el Sobrino" ("The Nephew"). Mérida was founded in 1542 by Montejo y León ("el Mozo") and named after the town of Mérida in Extremadura, Spain. It was built on the site of the Maya city of T'hó (/tʼχoʼ/), which was also called Ichkanzihóo or Ichcaanzihó (/iʃkan'siχo/; "City of Five Hills") in reference to its pyramids.


title: Mérida, Yucatán

text: Carved Maya stones from ancient T'ho were used to build the Spanish colonial buildings which are numerous in downtown Mérida; these stones are visible, for instance, in the walls of the main cathedral. Much of Mérida's architecture from the colonial period through the 18th century and 19th century is still standing in the "centro histórico" of the city. From colonial times through the mid-19th century, Mérida was a walled city intended to protect the Peninsular and Criollo residents from periodic revolts by the indigenous Maya. Several of the old Spanish city gates survive, but modern Mérida has expanded well beyond the old city walls.


title: Mérida, Yucatán

text: Late in the 19th century and the early 20th Century, the area surrounding Mérida prospered from the production of "henequén". For a brief period, around the turn of the 20th century, Mérida was said to house more millionaires than any other city in the world. The result of this concentration of wealth can still be seen today. Many large and elaborate homes still line the main avenue called "Paseo de Montejo", though few are occupied today by individual families. Many of these homes have been restored and now serve as office buildings for banks and insurance companies. Korean immigration to Mexico began in 1905 when more than a thousand people arrived in Yucatán from the city of Incheon. These first Korean migrants settled around Mérida as workers in henequen plantations.


title: Mérida, Yucatán

text: By the beginning of the 1900s manufacturing activities were mainly soap, tobacco products, leather, molasses, and rum.


title: Mérida, Yucatán

text: Completed in 1911 by Camilo and Ernesto Cámara Zavala, “Las Casas Gemelas” (The Twin Houses), are two side by side French and Spanish style mansions that remain from the early 20th Century. They are two of only a few houses that are still used as residences on Paseo Montejo from that era. They are owned by the Barbachano and Molina Méndez families. During the Porfiriato, the Barbachano house held cultural events that hosted artists, poets, and writers. In the mid-1900s, the Barbachanos hosted aristocrats including Princess Grace and Prince Ranier of Monaco, as well as first lady of the U.S., Jacqueline Kennedy.


title: Mérida, Yucatán

text: Mérida has one of the largest "centro histórico" districts in the Americas (surpassed only by Mexico City and Havana, Cuba). Colonial homes line the city streets to this day, in various states of disrepair and renovation; the historical center of Mérida is currently undergoing a minor renaissance as more and more people are moving into the old buildings and reviving their former glory.


title: Mérida, Yucatán

text: In August 1993, Pope John Paul II visited the city on his third trip to Mexico. The city has been host to two bilateral United States – Mexico conferences, the first in 1999 (Bill Clinton – Ernesto Zedillo) and the second in 2007 (George W. Bush – Felipe Calderón).


title: Mérida, Yucatán

text: In June 2007, Mérida moved its city museum to the renovated Post Office building next to the downtown market. The Museum of the City of Mérida houses important artifacts from the city's history, as well as an art gallery. Mérida hosted the VI Summit of Association of Caribbean States, in April 2014.


title: Mérida, Yucatán

text: Mérida is the cultural and financial capital of the Yucatán Peninsula, as well as the capital city of the state of Yucatán. In recent years, important science competitions and World events have been held in Mérida – FITA Archery World Cup Finals, the International Cosmic Ray Conference, a Physics Olympiad, etc.


title: Mérida, Yucatán

text: Mérida is located in the northwest part of the state of Yucatán, which occupies the northern portion of the Yucatán Peninsula. To the east is the state of Quintana Roo, to the west is the state of Campeche, to the north is the Gulf of Mexico, and far to the south is the state of Chiapas. The city is also located in the Chicxulub Crater. It has a very flat topography and is only above sea level. The land outside of Mérida is covered with smaller scrub trees and former "henequen" fields. Almost no surface water exists, but several cenotes (underground springs and rivers) are found across the state. Mérida has a "centro histórico" typical of colonial Spanish cities. The street grid is based on odd-numbered streets running east/west and even-numbered streets running north–south, with Calles 60 and 61 bounding the "Plaza Grande" in the heart of the city. The more affluent neighborhoods are located to the north and the most densely populated areas are to the south. The Centro Histórico area is becoming increasingly popular with Americans and other expatriates who are rescuing and restoring the classic colonial structures. In 2007 the "Los Angeles Times" recently noted this surge of interest in rescuing Mérida's historic downtown.


title: Mérida, Yucatán

text: Mérida features a tropical savanna climate (Köppen: "Aw"). The city lies in the trade wind belt close to the Tropic of Cancer, with the prevailing wind from the east. Mérida's climate is hot and its humidity is moderate to high, depending on the time of year. The average annual high temperature is , ranging from in December to in May, but temperatures often rise above in the afternoon during this period. Low temperatures range between in January to in May. It is most often a few degrees hotter in Mérida than in coastal areas due to its inland location and low elevation. The rainy season runs from June through October, associated with the Mexican monsoon which draws warm, moist air landward. Easterly waves and tropical storms also affect the area during this season.


title: Mérida, Yucatán

text: Mérida is the constitutional capital of the state of Yucatán. State government officials reside here. The municipal or local government is invested under the authority of a City Council ("Ayuntamiento") which it is seated at the Municipal Palace of Merida, located at the city's historic center.


title: Mérida, Yucatán

text: The City Council is presided by a municipal president or mayor, and an assembly conformed by a number of regents ("regidores") and trustees ("síndicos"). Renán Barrera Concha became Mayor on September 1, 2018.