title: Mouna Ragam

text: Sreeram made extensive use of frontal and profile close-ups, set against long shots with out-of-focus foregrounds. While filming Manohar's introductory scene, he had to lie on a bed sheet to film. The crew pulled the sheet, with Sreeram and the camera. The scene where Manohar plays a prank on Divya's father (Ra. Sankaran), which later became known as the "Mr. Chandramouli scene", was shot at Tic Tac, an open-air restaurant in Nungambakkam. Filming was also done at Madras' Presidency College, the Schmidt Memorial on Edward Elliot's Beach, and the Madras Literary Society. While filming the song "Oho Megam Vandhadho" which shows Divya dancing in the rain, Revathi tied a handkerchief around her wrist to cover her watch because she felt Divya would actually do that.


title: Mouna Ragam

text: The crew filmed in Delhi for two days, and the scenes set in Agra were shot in one day. Portions of "Panivizhum Iravu" were shot at the Taj Mahal in Agra, and those from "Mandram Vandha" were shot at the India Gate. The scenes involving Karthik were the last parts to be filmed, being shot in either a week or two. In post-production, Mohan's voice was dubbed by S. N. Surendar. The film's final length was .


title: Mouna Ragam

text: "Mouna Ragam" provides insight into the issues faced by married couples, exploring the plight and perception of divorce, how societies need to view the desires of women, and questions the agency of women. Film critic Baradwaj Rangan compared it to "Nenjathai Killathe" (1980), another story of a woman torn between the man she loves and the man she marries, "Andha 7 Naatkal" (1981) and its Hindi remake, "Woh Saat Din" (1983). Rakesh Mehar of "The News Minute" noted that one thing differentiating "Mouna Ragam" from "Andha 7 Naatkal" and similar films is that it remains focused on Divya. Kumuthan Maderya, writing for "PopMatters", described "Mouna Ragam" as a "chick flick", because like other chick flicks, the film allowed romance to blossom between Divya and Chandrakumar, rather than let divorce separate them; according to him, "chick flicks center on the romantic worldview of females while gratifying their hopes and dreams usually through a warm and fuzzy denouement".


title: Mouna Ragam

text: Manohar was part of a group involved in anti-government activities. Rangan drew similarities between his motives and those of characters in the Italian film "The Night of the Shooting Stars" (1982) and "Unaroo". The connection to "The Night of the Shooting Stars" is referenced when a poster of it appears in a scene where Manohar and his anarchist friends plan an event. According to Rangan, the scene where Divya is looking after Chandrakumar at the hospital reflects her traditional qualities; with her strengths, she is humane and vulnerable. Divya's mischievous nature is shown in a scene where she teaches a Sardar offensive Tamil phrases, which he says to Chandrakumar's boss.


title: Mouna Ragam

text: Revathi compared herself to Divya, saying that Divya believes in "living life to the fullest" and she was once like that. Sujatha Narayanan, writing for "The New Indian Express", described Chandrakumar as a "patient-understanding-and-poised-at-all-times" man, contrasting him with Manohar who she described as a "dashing, brave and epitome-of-the-word-'dude. She noted that Divya, like the female leads in most of Ratnam's films, is "practical with strong convictions" and the characters "go through their confusions unapologetically". According to Ratnam, the line ""Neenga thottaale kambilipoochi oorraa madhri irukku"" (When you touch me, it feels as if caterpillars are crawling on me), spoken by Divya to Chandrakumar, expressed how she would feel on her wedding night.


title: Mouna Ragam

text: Many critics have mentioned that "Mouna Ragam" background score suits its scenes and themes. According to Martin Clayton, Trevor Herbert and Richard Middleton's 2003 book, "The Cultural Study of Music: A Critical Introduction", "Oho Megam Vandhadho" resembled Broadway and MTV styles of singing and dancing, and the main songs combine American music with Indian vocals by S. Janaki. Sangeetha Devi Dundoo of "The Hindu" considered that Ratnam used rain in the film to accentuate the "childlike, free-spirited nature" of Divya. The sarangi and nadaswaram are used in the music accompanying Chandrakumar and Divya's wedding. In scenes of the couple sightseeing in Delhi, light synth-based music depicts them as modern tourists in their own country. The restaurant scene with Manohar and Divya includes awkwardly played sitar music, indicating the couple's emotions. Spanish music is used for the fight scene when Manohar attacks the politician's son.


title: Mouna Ragam

text: "The Hindu"'s Sruthi Radhakrishnan described "Panivizhum Iravu" as "one of those only-80s songs that served as a stand-in for sexual tension, where you'd have two people looking intensely at each other." Raveena Joseph of "The Hindu" noted that films in the 1980s which featured men stalking women, hoping to get them, were reflective of "the times where romances were covert and such discretion was necessary even in consensual encounters", citing Manohar stalking Divya in "Mouna Ragam" as an example. The film was Ratnam's first to follow the theme of a person moving to a strange place where they do not know the local language. Divya has a dilemma; since she does not know the language of Delhi, she can barely socialise with local people, and is in conflict with Chandrakumar, the only person with whom she can socialise. Rangan believed Manohar to be the first character in a Tamil film to invite a girl for a "cup of coffee", a form of dating. He contrasted it with "Oru Thalai Ragam" (1980), in which the protagonists barely spoke. Ratnam replied that although it was not uncommon to invite a girl for a cup of coffee in the 1980s, it was not reflected in mainstream Tamil cinema of the time.


title: Mouna Ragam

text: "Mouna Ragam" soundtrack was composed by Ilaiyaraaja with lyrics by Vaali. It was released by the Echo Records. According to "The Cultural Study of Music: A Critical Introduction", "Oho Megam Vandhadho" (featuring Divya dancing with several teenage girls) is a reworking of Gene Kelly's "Singin' in the Rain". "Nilaave Vaa" is the second song on both sides of the soundtrack's original LP record. The instrumental theme, which does not appear on that LP record, was partially inspired by the "Love Theme from Flashdance" (from the 1983 film "Flashdance").


title: Mouna Ragam

text: The majority of songs are set in Carnatic ragas; "Mandram Vandha" is set in Keeravani, with Natabhairavi notes. "Chinna Chinna Vanna Kuyil" is set in Gourimanohari, "Nilaave Vaa" is set in Sankarabharanam, and "Panivizhum Iravu" is set in Natabhairavi. All the songs attained immense popularity. "Mandram Vandha" was later adapted by Ilaiyaraaja and used twice in the 2007 Hindi film, "Cheeni Kum" as its title track and "Sooni Sooni". The film and its soundtrack was dubbed in Telugu, under the same name, whose adapted lyrics were written by Rajasri.


title: Mouna Ragam

text: "Mouna Ragam" was publicised with a shot of Revathi clinging to a lamp post and singing, which Ratnam confirmed as being inspired by "Singin' in the Rain". Before the film's release, a Central Board of Film Certification member wanted it to receive an "A" (adults-only) certificate because the female lead asks for a divorce; after much deliberation, it received a "U" certificate. "Mouna Ragam" was released on 15 August 1986, coinciding with India's Independence Day. Despite opening to modest audiences, it picked up and became a box-office success, running for over 175 days in theatres, thereby becoming a silver jubilee film. Ratnam considered "Mouna Ragam" his first commercial success. While the film performed very well in urban areas, it was largely shunned by audiences in rural areas.


title: Mouna Ragam

text: The film was critically acclaimed, especially for its realistic portrayal of urban Tamil people. In a 31 August 1986 review, the review board of the Tamil magazine "Ananda Vikatan" praised Revathi and Mohan's performances, the film's camera work, music and lack of masala, giving "Mouna Ragam" a score of 43 out of 100. Jeyamanmadhan of "Kalki" wrote that the relief that one gets after getting up from watching the film would get rid of all the irritants in the film and felt that was enough. Kaviya Shetty of "India Today" wrote in 1994, "["Mouna Ragam"] found the perfect formula of a strong storyline and great music, presented in a fresh visual style that caught the audience by surprise".


title: Mouna Ragam

text: "Mouna Ragam" was dubbed in Telugu and released with the same title in 1987, which was also a success. It was remade in Hindi as "Kasak" in 1992, and in Kannada in 1999 as "Chandrodaya".


title: Mouna Ragam

text: "Mouna Ragam" was screened at the 11th International Film Festival of India, the only Tamil entry. It has also been screened at other film festivals, including Mani Ratnam's Love Films at London's National Film Theatre in 2002, a Retrospective of Mani Ratnam's Films at the 2002 Calcutta Film Festival and at the 2002 Locarno Film Festival. An enhanced 5.1 Digital Dolby soundtrack was released in May 2008 by Bayshore Records.


title: Mouna Ragam

text: "Mouna Ragam" emerged a milestone of Tamil cinema and Mani Ratnam's breakthrough film. It has been acclaimed for combining box-office success with elements of an art film. The film introduced techniques such as soft-focus shots, flare filters and backlighting, which became popular in Tamil cinema. Ratnam continued using these techniques in his later films, notably "Nayakan" (1987) and "Agni Natchathiram" (1988). "Mouna Ragam"s theme of a person moving to a new place where they do not know the local language was replicated in Ratnam's later films like "Nayakan", "Roja" (1992) and "Bombay" (1995). It was also Ratnam's first film to make extensive use of staccato dialogue; this became another recurring feature in his later films. The film became a major breakthrough for Karthik despite his role being a cameo, and his "Mr. Chandramouli" dialogue became popular. A feature film, released in 2018 and starring him, was named after this dialogue. The character of Chandramouli became one of Sankaran's best known roles.


title: Mouna Ragam

text: According to a Rediff.com article, "The Most Memorable Mani Movies", "Mouna Ragam" was "arguably the film that announced Mani Ratnam to the Tamil film industry as a talent to watch out for. An excellent script by Ratnam himself, [cinematography by P. C. Sreeram] and a lilting score by [Ilaiyaraaja] made it a hit with both critics and moviegoers". Pavithra Srinivasan of the same website said, "It took a Mani Ratnam to move away from clichéd romantic dialogues and capture subtle nuances that add so much richness to the story, introduce proper, three dimensional characters that lived breathed and sorrowed like everyone else". "Deccan Chronicle" listed Karthik and Revathi on its "Top 10 Jodis" of Tamil cinema; they "made a fresh pair and were adored by the youth, especially the college students. Their awesome on-screen chemistry in "Mouna Ragam" was a talking point back then". For the April 2013 centenary of Indian cinema, "Forbes India" included Revathi's performance in its list, "25 Greatest Acting Performances of Indian Cinema".


title: Mouna Ragam

text: "Mouna Ragam" has influenced countless films, particularly regarding the trope of the bride or groom being reluctantly married. These include "Hum Dil De Chuke Sanam" (1999), "Vallamai Tharayo" (2008), "Rab Ne Bana Di Jodi" (2008), "Tanu Weds Manu" (2011), "Raja Rani" (2013) where both the male and female leads have past lovers, "Bangalore Days" (2014) where a man who is unable to forget his past love and accept his wife, and "Maalai Naerathu Mayakkam" (2016).


title: Mouna Ragam

text: Karthi said that his character in "Naan Mahaan Alla" (2010) was similar to Karthik's "moody yet jovial" character in "Mouna Ragam". Sri Divya called Revathi's character an influence on her role in "Mallela Theeram Lo Sirimalle Puvvu" (2013). Vaibhav Reddy compared his character in "Kappal" (2014) to Manohar in "Mouna Ragam" because of their shared effervescence. Director B. V. Nandini Reddy said that the story of a bride unhappy with her husband in "Mouna Ragam" inspired her to make "Kalyana Vaibhogame" (2016), where neither the bride nor the bridegroom is interested in marriage.


title: Mouna Ragam

text: The scene where Manohar tries to declare his love for Divya through the college intercom in response to her challenge was parodied in "Thamizh Padam" (2010). Director R. S. Prasanna described one scene in "Kalyana Samayal Saadham" (2013) where the male lead meets his father-in-law at a café as an ode to the "Mr. Chandramouli" scene. In "Master" (2021), JD (Vijay) lies about his past but from Manohar's perspective.


title: Calais Campbell

text: Calais Mark Campbell (born September 1, 1986) is an American football defensive end for the Baltimore Ravens of the National Football League (NFL). He played college football at Miami and was drafted by the Arizona Cardinals in the second round of the 2008 NFL Draft.


title: Calais Campbell

text: Campbell played his high school football at South High School in Denver, Colorado. Widely regarded as one of the nation's top defensive end prospects, he was ranked as the tenth-best strongside defensive end by Rivals.com and the seventh-best defensive end by Scout.com. He amassed a state-record total of 57 sacks in his career at South High School.


title: Calais Campbell

text: In addition to football, Campbell also starred on the school's basketball team; averaging 22.7 points (fourth best in Colorado), 16.0 rebounds per game (led the state) and 3.3 blocks per game, he was an All-State basketball selection as a junior. Campbell also competed in track & field at South, qualifying for the state meet in the discus and shot put in 2003. His track-and-field personal bests: in the long jump, in the shot put, in the discus and in the triple jump.


title: Calais Campbell

text: Campbell chose Miami over Colorado State, Nebraska, Louisiana State, Michigan, Oklahoma, and San Diego State.


title: Calais Campbell

text: Campbell first saw playing time at Miami in the 2005 season. In 11 games, he recorded 24 total tackles, 2.5 sacks, and three passes defensed. In the 2006 season, he had 55 total tackles, 10.5 sacks, four passes defensed, and three forced fumbles. He recorded at least three sacks in a single game on three occasions in the 2006 season. In his final season with the Hurricanes in 2007, he had 50 total tackles, 6.5 sacks, three passes defensed, and one interception, which came against Marshall in the season opener.


title: Calais Campbell

text: The Arizona Cardinals selected Campbell in the second round (50th overall) of the 2008 NFL Draft. Campbell was the sixth defensive end drafted in 2008. The Arizona Cardinals had no immediate need for a starting-caliber defensive end, but chose to make a value pick and draft Campbell after he unexpectedly fell out of the first round and was considered the top player available at the time of their selection.


title: Calais Campbell

text: On July 24, 2008, the Arizona Cardinals signed Campbell to a four-year, $3.40 million contract with $1.68 million guaranteed and a signing bonus of $484,500.


title: Calais Campbell

text: Campbell entered training camp slated as a backup defensive end and competed against Bryan Robinson and fellow rookie Kenny Iwebema for a spot in the rotation. Head coach Ken Whisenhunt officially named Campbell a backup defensive end to start the regular season, behind veterans Darnell Dockett and Antonio Smith.


title: Calais Campbell

text: Campbell made his professional regular season debut in the Cardinals' season-opener at the San Francisco 49ers and assisted on a tackle in their 23–13 victory. The following week, Campbell collected a season-high four solo tackles in the Cardinals' 31–10 victory against the Miami Dolphins in Week 2. During Week 16, Campbell tied his season-high of four solo tackles during a 47–7 loss at the New England Patriots.


title: Calais Campbell

text: Campbell completed his rookie season in with 28 combined tackles (23 solo), a pass defended, a forced fumble, and a fumble recovery in 16 games and zero starts.


title: Calais Campbell

text: The Cardinals finished atop the NFC West with a 9–7 record and qualified for a playoff berth in 2008. On January 3, 2009, Campbell appeared in his first NFL playoff game and made two combined tackles during a 30–24 victory against the Atlanta Falcons in the NFC . The Cardinals reached Super Bowl XLIII after defeating the Carolina Panthers 33–13 in the and defeating the Philadelphia Eagles 32–25 in the . On February 1, 2009, Campbell appeared in Super Bowl XLIII and recorded two combined tackles as the Cardinals lost 27–23 in a closely contested match that was decided as time expired. Campbell finished the playoffs with eight combined tackles (seven solo) and a pass deflection.


title: Calais Campbell

text: On February 9, 2009, head coach Ken Whisenhunt fired defensive coordinator Clancy Pendergast due to the defense's inability to hold onto a 23–20 lead in the fourth quarter of Super Bowl XLIII. Campbell entered training camp slated as a starting defensive end after Antonio Smith departed for the Houston Texans during free agency. Defensive coordinator Billy Davis opted to switch from a base 4-3 defense to a base 3-4 defense. Head coach Ken Whisenhunt named Campbell the starting left defensive end, opposite Darnell Dockett and alongside nose tackle Bryan Robinson, to begin the regular season.


title: Calais Campbell

text: Campbell made his first career start in the Cardinals' season-opener against the San Francisco 49ers and recorded a season-high six solo tackles and deflected a pass in their 20–16 loss. The following week, Campbell made a tackle, broke up a pass, and was credited with half a sack during a 31–17 victory at the Jacksonville Jaguars in Week 2. His first career sack was with teammate Adrian Wilson, as the two brought down quarterback David Garrard in the fourth quarter. On October 18, 2009, Campbell recorded three combined tackles and a season-high 1.5 sacks during a 27–3 win at the Seattle Seahawks in Week 6. He sacked quarterback Matt Hasselbeck for a seven-yard loss in the third quarter to mark the first solo sack of his career. In Week 8, he collected a season-high seven combined tackles (six solo) in the Cardinals' 34–21 loss to the Carolina Panthers. Campbell finished the 2009 season with a total of 45 combined tackles (37 solo), seven sacks, five passes defensed, and a forced fumble in 16 games and 15 starts.


title: Calais Campbell

text: The Cardinals finished atop the NFC West with a 10–6 record and defeated the Green Bay Packers in overtime 51–45 during the NFC . On January 16, 2010, Campbell started his first career playoff game and made three solo tackles in a 45–14 loss at the New Orleans Saints in the NFC .


title: Calais Campbell

text: Head coach Ken Whisenhunt chose to retain Campbell and Darnell Dockett as the starting defensive ends to begin the regular season, along with nose tackle Bryan Robinson.


title: Calais Campbell

text: Campbell was sidelined during the Cardinals' Week 12 loss to the San Francisco 49ers after injuring his ankle the previous week. On November 29, 2010, Campbell recorded a season-high 11 combined tackles (nine solo) and sacked quarterback Jimmy Clausen during a 19–12 loss at the Carolina Panthers in Week 15. The following week, he made two solo tackles and a sack in the Cardinals' 27–26 win against the Dallas Cowboys in Week 16. It marked his second consecutive game with a sack and his sixth sack of the season. Campbell finished the season with 60 combined tackles (46 solo), six sacks, and two pass deflections, and a fumble recovery in 15 games and 15 starts.


title: Calais Campbell

text: On January 6, 2011, head coach Ken Whisenhunt announced the firing of defensive coordinator Billy Davis after the Cardinals finished with a 5–11 record and allowed the third most points in the league in 2010. Head coach Ken Whisenhunt hired Pittsburgh Steelers' secondary coach, Ray Horton, as the Cardinals new defensive coordinator. Horton employed a base 3-4 defense that utilized multiple fronts. Horton retained Campbell and Darnell Dockett as the starting defensive ends to start the season, along with nose tackle Dan Williams.


title: Calais Campbell

text: On September 25, 2011, Campbell made a season-high ten combined tackles (five solo) and was credited with a season-high 2.5 sacks on quarterback Tarvaris Jackson during a 13–10 loss at the Seattle Seahawks in Week 3. In Week 9, he collected six solo tackles and made two sacks on quarterback Sam Bradford in the Cardinals' 19–13 win against the St. Louis Rams. The following week, he made two solo tackles, two pass deflections, and made his first career interception off a pass by quarterback Michael Vick in the third quarter of a 21–17 victory at the Philadelphia Eagles in Week 10. He finished the season with a career-high 72 combined tackles (53 solo), ten pass deflections, eight sacks, two forced fumbles, and an interception in 16 games and 16 starts.


title: Calais Campbell

text: He also appeared on special teams and blocked three field goals during the season. Campbell predominantly lined up in the five-technique in his first season under Ray Horton.


title: Calais Campbell

text: On March 2, 2012, the Cardinals placed their non-exclusive franchise tag to Campbell for the 2012 season. On May 10, 2012, the Arizona Cardinals signed Campbell to a five-year, $55 million contract with $31 million guaranteed and a signing bonus of $15 million.


title: Calais Campbell

text: Head coach Ken Whisenhunt retained Campbell, Darnell Dockett, and nose tackle Dan Williams as the starting defensive linemen to begin the regular season. On September 16, 2012, Campbell collected a season-high ten combined tackles (seven solo) and recorded two sacks on quarterback Tom Brady in a 20–18 win at the New England Patriots in Week 2. Campbell was inactive for three games (Weeks 11–13) due to an injury to his right calf. In Week 16, he collected eight combined tackles, deflected a pass, and recorded a sack during a 28–13 loss to the Chicago Bears. The following week, Campbell made two solo tackles and a sack in the Cardinals' 27–13 loss at the San Francisco 49ers in Week 17. Campbell completed the 2012 season with 65 combined tackles (50 solo), 6.5 sacks, and six pass deflections in 13 games and 12 starts.


title: Calais Campbell

text: On January 8, 2013, the Arizona Cardinals fired general manager Rod Graves and head coach Ken Whisenhunt after the team finished last in their division with a 5–11 record in 2012. On January 18, 2013, it was reported that defensive coordinator Ray Horton demanded his release after Bruce Arians was hired as the new head coach instead of Horton. Head coach Bruce Arians officially named Campbell and Darnell Dockett the starting defensive ends to begin the 2013 season.


title: Calais Campbell

text: On October 6, 2013, Campbell recorded four solo tackles, two sacks, and earned his first career safety during a 22–6 victory against the Carolina Panthers in Week 4. He sacked quarterback Cam Newton for a five-yard loss in the endzone to record a safety in the third quarter. In Week 7, he collected a season-high eight combined tackles in a 34–22 loss to the Seattle Seahawks. On December 22, 2013, Campbell recorded four combined tackles and sacked quarterback Russell Wilson twice to tie his season-high during a 17–10 win at the Seattle Seahawks in Week 16. Campbell started all 16 games in 2013 and recorded 58 combined tackles (45 solo), nine sacks, six passes defended, two fumble recoveries, a forced fumble, and a safety. The Cardinals' new defensive coordinator, Todd Bowles, retained the base 3-4 defense, but also used multiple fronts with an emphasis on blitzing. Campbell was continually used as a defensive end and also lined up at defensive tackle in the three-technique for 8.4% of his defensive snaps.


title: Calais Campbell

text: Defensive coordinator Todd Bowles retained Campbell as the starting left defensive end to start the regular season, alongside nose tackle Dan Williams and right defensive end Frostee Rucker.


title: Calais Campbell

text: On September 16, 2014, Campbell collected a season-high ten solo tackles and a sack during a 25–14 win at the New York Giants. In Week 5, Campbell recorded two solo tackles, deflected a pass, and made the second interception of his career in the Cardinals' 41–20 loss at the Denver Broncos. His interception came off a pass attempt by quarterback Peyton Manning and was a screen pass intended for running back Montee Ball in the second quarter. Campbell exited in the third quarter due to a leg injury he sustained on a chop block by tight end Julius Thomas. Head coach Bruce Arians was asked about the chop block and stated, "the dirtiest play I have seen in 37 years of coaching football!" Campbell was diagnosed with a sprained MCL and was sidelined for the next two games (Weeks 6–7). On November 23, 2014, Campbell made six combined tackles and had a career-high three sacks on quarterback Russell Wilson during the Cardinals' 19–3 loss at the Seattle Seahawks in Week 12. On December 24, 2014, it was announced that Campbell was voted to the Pro Bowl to mark the first Pro Bowl selection of his career.


title: Calais Campbell

text: Campbell finished the season with 58 combined tackles (48 solo), seven sacks, three passes defended, an interception, and a forced fumble in 14 games and 14 starts.


title: Calais Campbell

text: The Cardinals finished second in the NFC West with an 11–5 record and earned a Wild Card berth to mark their first postseason appearance since 2009. On January 3, 2015, Campbell made four combined tackles in the Cardinals 27–16 loss in the at the Carolina Panthers. He was ranked 99th by his fellow players on the NFL Top 100 Players of 2015.


title: Calais Campbell

text: Head coach Bruce Arians promoted Cardinals' linebackers coach James Bettcher to defensive coordinator after Todd Bowles accepted a job as the head coach for the New York Jets. Bettcher chose to retain Campbell and Frostee Rucker as the starting defensive ends with Josh Mauro and Rodney Gunter sharing the role at nose tackle.


title: Calais Campbell

text: In Week 4, Campbell collected a career-high 11 combined tackles (ten solo) and was credited with half a sack during a 24–22 loss to the St. Louis Rams. On October 21, 2015, it was reported that Campbell had his position reclassified as defensive tackle after lining up on the interior defensive line for 70.8% of his plays during the first six games. Campbell gave his approval when the Cardinals asked him to primarily play inside and had his position changed to reflect the move to defensive tackle on the team's depth chart. Although Campbell was listed as a defensive tackle he stated his duties would remain the same and he would still line up at defensive end when required. On December 22, 2015, Campbell was selected to the 2016 Pro Bowl. It became his second consecutive Pro Bowl selection and his first as a defensive tackle. On December 27, 2015, he recorded six combined tackles and had a season-high 2.5 sacks on Aaron Rodgers as the Cardinals routed the Green Bay Packers by a score of 38–8 in Week 16.


title: Calais Campbell

text: Campbell finished the 2015 season with 61 combined tackles (46 solo), five sacks, three passes defensed, and a forced fumble in 16 games and 16 starts. Campbell was lined up in multiple positions and also remained on the field during dime packages. The Cardinals had moderate success in their first season under Bettcher and finished fifth in yards allowed. He was ranked 71st by his fellow players on the NFL Top 100 Players of 2016.


title: Calais Campbell

text: Head coach Bruce Arians named Campbell the starting defensive tackle to begin the season, along with Rodney Gunter. On October 6, 2016, Campbell recorded four combined tackles, two sacks, deflected a pass, made an interception, and a safety during a 33–21 win at the San Francisco 49ers in Week 5. He intercepted a pass attempt by quarterback Blaine Gabbert in the second quarter, that was intended for tight end Garrett Celek, and registered a safety after sacking Gabbert for a one-yard loss in the end zone during the fourth quarter. In Week 8, Campbell collected a season-high nine combined tackles during a 30–20 loss at the Carolina Panthers. In Week 14, Campbell recorded four solo tackles, two sacks, recovered a fumble, and scored his first career touchdown in a 48–41 loss to the New Orleans Saints. Quarterback Drew Brees had the ball stripped by Markus Golden and it was recovered by Campbell and returned for a 53-yard touchdown in the second quarter. He recorded 53 combined tackles (46 solo), eight sacks, six passes defensed, three fumble recoveries, two forced fumbles, a safety, an interception, one cheap on Ryan Tannehill and a touchdown in 16 games and 16 starts. He was ranked 83rd by his fellow players on the NFL Top 100 Players of 2017.


title: Calais Campbell

text: Campbell became an unrestricted free agent following the 2016 season and received interest from multiple teams, including the Arizona Cardinals, Denver Broncos, and Jacksonville Jaguars. The Cardinals offered Campbell a contract that amounted to $9 million per year. His second best offer was from the Denver Broncos, his hometown team, and amounted to an average of $13 million per year.


title: Calais Campbell

text: On March 9, 2017, the Jacksonville Jaguars signed Campbell to a four-year, $60 million contract that includes $30 million guaranteed and a signing bonus of $6 million.


title: Calais Campbell

text: Head coach Doug Marrone chose to move Campbell back to defensive end and named him the starter to begin the regular season, opposite Yannick Ngakoue. Campbell and Ngakoue joined defensive tackles Malik Jackson and Abry Jones.


title: Calais Campbell

text: Campbell started in the Jaguars' season-opener, against the Houston Texans, and recorded six combined tackles and made a career-high four sacks on quarterback Tom Savage in a 29–7 road victory. Campbell's four sacks set a franchise record and the defense also set a franchise record with a combined ten sacks. His performance earned him AFC Defensive Player of the Week. During the course of the season, the Jaguars' defense earned the moniker "Sacksonville". In Week 13, Campbell brought his sack total to 12.5 sacks, which set a Jaguars franchise record for most sacks in a season. During Week 12, Campbell returned to Arizona to face his former team and recorded three solo tackles and recovered a fumble for a touchdown as the Jaguars were defeated by the Arizona Cardinals 27–23 in Week 12. During the fourth quarter, Cardinals' quarterback Blaine Gabbert was stripped by Yannick Ngakoue and Campbell was able to recover the ball and returned it 10 yards for a touchdown. On December 17, 2017, Campbell made five solo tackles, a pass deflection, and two sacks during a 45–7 victory against the Houston Texans. The game marked his fourth multi-sack performance of the 2017 season. The following week, he collected a season-high eight combined tackles and deflected a pass during a 44–33 loss at the San Francisco 49ers in Week 16. On December 19, 2017, Campbell was voted to the 2018 Pro Bowl, which became his third Pro Bowl selection.


title: Calais Campbell

text: Campbell finished the season with 67 combined tackles (47 solo), a career-high 14.5 sacks, three pass deflections, three forced fumbles, a fumble recovery, and a touchdown in 16 games and 16 starts.


title: Calais Campbell

text: The Jaguars finished atop the AFC South with a 10–6 record and earned a playoff berth. On January 7, 2018, Campbell recorded six combined tackles during a 10–3 victory against the Buffalo Bills in the AFC Game. The Jaguars went on to defeat the Pittsburgh Steelers 45–42 in the AFC before being eliminated from the playoffs after losing 24–20 at the New England Patriots during the AFC Championship Game. He was ranked 14th by his fellow players on the NFL Top 100 Players of 2018.


title: Calais Campbell

text: In the 2018 season, Campbell finished with 10.5 sacks, 72 total tackles, 22 quarterback hits, two passes defensed, and one forced fumble. The Jaguars did not retain their overall success from the previous season, this time finishing with a 5–11 record. Despite the Jaguars' disappointing season, Campbell was named to his fourth career Pro Bowl. He was ranked 54th by his fellow players on the NFL Top 100 Players of 2019.


title: Calais Campbell

text: During Week 3 against the Tennessee Titans, Campbell sacked Marcus Mariota thrice as the Jaguars won 20–7, earning him AFC Defensive Player of the Week. In the regular season finale against the 2019 Indianapolis Colts, Campbell recovered a fumble lost by Jacoby Brissett and returned it for an 8-yard touchdown during the 38–20 victory. He was named to the Pro Bowl for the 2019 season. He was ranked 79th by his fellow players on the NFL Top 100 Players of 2020. Campbell was named to the Pro Football Hall of Fame All-Decade Team for the 2010s.


title: Calais Campbell

text: On March 19, 2020, the Jaguars traded Campbell to the Baltimore Ravens for a 2020 fifth-round pick originally acquired from the Atlanta Falcons. Shortly after the trade, Campbell signed a one-year contract extension.


title: Calais Campbell

text: In Week 2 against the Houston Texans, Campbell recorded his first sack as a Raven on Deshaun Watson during the win. In the Ravens' Week 6 win over the Philadelphia Eagles, Campbell was credited with four tackles for loss, four quarterback hits and sacked Carson Wentz three times. As a result, he was named the AFC Defensive Player of the Week. He was placed on the reserve/COVID-19 list by the Ravens on November 25, 2020, and activated on December 5, 2020. He was named to the Pro Bowl.


title: Calais Campbell

text: In Week 5 against the Indianapolis Colts, Campbell blocked Rodrigo Blankenship's field goal and recovered late in the fourth quarter, helping the Ravens continue their rally as they were down by eight points at the time. The Ravens would win the game 31–25 in overtime. In the 2021 season, Campbell appeared in and started 15 games. He finished with 49 total tackles, 1.5 sacks, one pass defensed, and 12 quarterback hits


title: Calais Campbell

text: Campbell was born in Denver, Colorado, to Charles and Nateal Campbell. He was raised with seven siblings. He has two sisters, Kimba Blaylock and Keyonne Campbell, and five brothers: Jamar, Raj, Ciarre, Severin, and Jared. His father, Charles Campbell, died in late 2003. Jared Campbell, a touring stand-up comedian, also played football with Calais at both University of Miami and Arizona Cardinals as a defensive back. His brothers Ciarre and Raj played college football at Colorado State and Butte Junior College, respectively. His brother Severin played at the University of Montana. In December 2007, Campbell graduated from the University of Miami with a degree in sociology. On January 21, 2015, it was announced that Calais Campbell had given $1.6 million to the Hurricanes to establish an endowed scholarship for defensive linemen in perpetuity at the University of Miami. He appeared on the first episode of seventh season of "The League", appearing with former teammate Tyrann Mathieu.


title: Dan Smith (singer)

text: Daniel Campbell Smith (born 14 July 1986) is an English singer, songwriter and record producer, best known as the founder, lead singer and primary songwriter of the English pop rock band Bastille. The band formed in 2010 and gained mass popularity in 2013 when the song "Pompeii" was released with their album "Bad Blood". The band then released their second album, "Wild World" in September 2016. In June 2019, the band released their third album "Doom Days".


title: Dan Smith (singer)

text: Smith attended King's College School and the University of Leeds in Leeds, West Yorkshire, where he graduated with a degree in English Language and Literature while also writing about film and music for the Leeds student newspaper. A film obsessive from a young age, he originally wanted to be a director or editor until admitting he was "more of a fan than a filmmaker".


title: Dan Smith (singer)

text: At age fifteen, Smith started writing songs on the piano and his laptop in his bedroom, but kept his music secret from his friends and family until he was persuaded by a friend to enter the Leeds Bright Young Things competition in 2007, which he ultimately became a finalist in. His early recordings included "Alchemy", "Words Are Words", "Irreverence", and "Dictator". Smith did not achieve mainstream success in his solo career but continued writing songs both alone and with his close friend and roommate Ralph Pelleymounter of the band To Kill a King. The two formed a side project called "Annie Oakley Hanging" which was described as "cowboy-like" by Pelleymounter.


title: Dan Smith (singer)

text: After finishing his studies, Smith returned to London, where he continued pursuing his solo career, and eventually formed Bastille with Chris "Woody" Wood, Kyle Simmons, and Will Farquarson. Bastille has released four albums called "Bad Blood", "Wild World", "Doom Days" and "Give Me The Future", the latest of which was released 4 February 2022.


title: Dan Smith (singer)

text: In 2015, Smith featured as vocalist for the song "La Lune," produced and written by the French electronic musician Madeon for Madeon's 2015 album "Adventure". In the same year, Smith co-wrote and provided vocals on "Better Love" with Foxes, which was released 4 September 2015.


title: Dan Smith (singer)

text: Smith was part of the music video for the Charli XCX single 'Boys' which was released on 26 July 2017.


title: Dan Smith (singer)

text: He featured in the December 2017 ITV programme of "The Nation's Favourite" series which found out the nation's favourite Elton John song.


title: Dan Smith (singer)

text: At the 2019 Brit Awards, Smith performed a duet with American artist, Pink, of her song, "Just Give Me a Reason", as part of her medley performance.


title: Dan Smith (singer)

text: In November 2019, a cover of the REO Speedwagon song "Can't Fight This Feeling" sung by Smith was used in the John Lewis & Partners 2019 Christmas advert.


title: Dan Smith (singer)

text: Smith is a fan of the TV series "Twin Peaks", and of one of its creators, David Lynch. The show inspired one of his first recorded songs, "Laura Palmer" and Bastille's first Virgin Records single "Overjoyed". Smith has said that his earlier work was influenced by Regina Spektor.


title: Dan Smith (singer)

text: Smith writes and arranges some of Bastille's songs, apart from remixes and covers, and worked with friend Mark Crew to produce "Bad Blood" and "Wild World". He plays the piano, keyboard, percussion, and melodica. His original, "Dan Smith Piano" was stolen in 2010.


title: Dan Smith (singer)

text: During the COVID-19 pandemic in 2020, Smith performed music live on Instagram, and also set up a film club named 'Distraction Tactics', inspired by different countries around the world; each week the club visits a different country and film. Its aim is to provide distraction and happiness to those in need of some relief from social distancing and isolation.


title: Andrea Radrizzani

text: Andrea Radrizzani (born 10 September 1974) is an Italian businessman and the majority owner of Premier League football club Leeds United. He is also the chairman and founder of the sports broadcasting group Eleven Sports.


title: Andrea Radrizzani

text: Radrizzani was born in Rho, a metropolitan area of Milan. He graduated with a degree in public relations from IULM University in 1996. Growing up passionate about football, he supported Juventus in his childhood and adolescence.


title: Andrea Radrizzani

text: A self-made businessman, Radrizzani began his career in sports media in 1999 with digital sports content distributor Media Partners and founded Media Partners’ China business.


title: Andrea Radrizzani

text: He co-founded MP & Silva in 2004 from Singapore, which went on to become an international sports rights company with 20 offices around the world, working in partnership with rights holders, including the Premier League, UEFA, F1, La Liga, NBA and WSBC.


title: Andrea Radrizzani

text: Radrizzani led media rights distribution agreements with selected Serie A teams in 2004, before acquiring the rights for the majority of Serie A teams in 2006. MP & Silva went on to build out its European football rights portfolio in Asia. In 2010, Radrizzani negotiated a new media rights partnership with Arsenal FC. The following year, he helped MP & Silva acquire pan-European rights for the French Open. In 2013, Radrizzani led MP & Silva's negotiations to secure the Premier League's broadcast rights in 51 territories, including the Middle East. The agency also bought Formula One rights in MENA and some selected European countries. Radrizzani was also responsible for leading rights distribution deals with Roland Garros, Bundesliga, La Liga, Ligue 1 among others.


title: Andrea Radrizzani

text: In 2014, Radrizzani stepped back from day-to-day MP & Silva operations. In May 2016, following the $1 billion sale of MP & Silva to a Chinese investment group, Radrizzani was appointed vice chairman of MP & Silva. On 17 October 2018, the High Court ordered the winding-up of MP & Silva.


title: Andrea Radrizzani

text: Radrizzani founded the investment platform Aser Ventures in 2015. Through Aser, Radrizzani has gone on to invest in existing sports, media and entertainment companies in addition to launching his own ventures including Leeds United, broadcaster Eleven Sports, Whistle Sports, Neo Studios and LIVENow.


title: Andrea Radrizzani

text: Through Aser, Radrizzani launched the international sports broadcaster Eleven Sports in 2015. Eleven has channels in Belgium, Luxembourg, Portugal, Poland, Italy, UK, Taiwan, Myanmar and Japan; and a rights portfolio that includes La Liga, Serie A, the Bundesliga, Premier League, UEFA Champions League and Formula 1.


title: Andrea Radrizzani

text: In January 2017, through Aser, Radrizzani made an investment in 50 per cent of the share capital of Leeds United, making him co-owner of the club.


title: Andrea Radrizzani

text: On 23 May 2017, Radrizzani announced the 100% buyout of Leeds United, buying the remaining 50% shares from previous co-owner Massimo Cellino, with Radrizzani taking full ownership of the club. Radrizzani's ownership of the club got off to a dramatic start; on 25 May, only two days after the takeover, and the day before Leeds were set to activate the option to extend head coach Garry Monk's contract, Monk resigned as Leeds United head coach, with new owner Radrizzani saying that Monk's decision to quit the club had been a 'shock'. After taking over the club he made changes to Leeds' backroom staff, including appointing Victor Orta as director of football, Ivan Bravo as Director of Strategy and Angus Kinnear as Chief Executive.


title: Andrea Radrizzani

text: On 15 June 2017, Radrizzani appointed his first head coach when APOEL manager Thomas Christiansen was announced as the new head coach of Leeds United to replace Monk, with the club announcing that they "wanted to appoint someone who can help us create a winning culture at the club and unite everyone connected with Leeds United, from the players to the supporters".


title: Andrea Radrizzani

text: On 26 June, Radrizzani brought back Leeds Ladies to Leeds United ownership to become Leeds United Ladies again after the club had previously become its own entity after previous owner Massimo Cellino decided to stop Leeds United funding in 2014.


title: Andrea Radrizzani

text: On 28 June 2017, Radrizzani completed the purchase of Elland Road, making the stadium the property of Leeds United for the first time since 2004.


title: Andrea Radrizzani

text: On 3 January 2018, Radrizzani announced an official partnership for Leeds with Aspire Academy in Qatar. Aspire own Spanish team Cultural Leonesa who have seen Leeds players Yosuke Ideguchi and Ouasim Bouy both join them on loan as part of the unique partnership.


title: Andrea Radrizzani

text: On 24 January 2018, Radrizanni introduced a new Leeds United badge which would be worn for the 2018/19 season onwards depicting the "Leeds Salute". However, the design of the new badge attracted criticism from huge numbers of fans, resulting in an online petition over 77,000 signatures strong against the design's introduction. Radrizzani and the club decided to "re-open the consultation process" in light of the poor reception the new crest engendered.


title: Andrea Radrizzani

text: On 4 February 2018, Head Coach Thomas Christiansen was dismissed by Radrizzani, despite a promising start to his reign, after a poor run of results and with the team tenth in the table. On 6 February 2018, Radrizzani appointed Barnsley Manager Paul Heckingbottom as the new head coach of Leeds United on an 18-month contract to replace Christiansen.


title: Andrea Radrizzani

text: On 7 March, towards the end of Leeds' 0–3 defeat against Wolverhampton Wanderers, just before the final whistle, Radrizzani in a series of Twitter posts, questioned the legality and fairness of the competition. On 12 March, Radrizzani made public his decision to seek clarity from the Football League regarding league leaders Wolverhampton Wanderers, to seek clarification of the link with Wolves and 'super agent' Jorge Mendes.


title: Andrea Radrizzani

text: In March 2018, Radrizzani announced that Leeds United would be going on a post-season tour of Myanmar in May 2018 to play two friendlies. However, the tour announcement drew criticism nationally and from MP's and Amnesty International due to the political situation in the country. Radrizzani defended the choice of location, declaring that 'This is about people not governments'.


title: Andrea Radrizzani

text: In Radrizzani’s first season as sole owner (2017–18), having being top of the League for the first quarter of the season, and dropping to fifth at the halfway point, Leeds missed out on playoffs completely after a disappointing run of form in the second half of the season, finishing thirteenth in the table.


title: Andrea Radrizzani

text: On 24 May 2018, Radrizzani and Leeds United announced that 49ers Enterprises had bought shares in the club to become a minority investor (49's Enterprises is the business arm of the NFL side San Francisco 49ers owned by Denise DeBartolo York, Jed York and John York).


title: Andrea Radrizzani

text: Head Coach Paul Heckingbottom was sacked by Radrizzani on 1 June 2018, having been at the club for just four months.


title: Andrea Radrizzani

text: Argentine manager Marcelo Bielsa was named by Radrizzani as the club's new head coach on 15 June, signing a two-year contract with option of a third year, after two weeks of negotiations with the club. In doing so he became the highest-paid manager in Leeds United history.


title: Andrea Radrizzani

text: Radrizzani entered late talks to buy Italian Serie B side F.C. Bari 1908 in July 2018, to become a co-owner/investor, but pulled out of the deal, because of a financial deadline due to Bari's financial situation. On 16 July 2018 Radrizzani revealed that “Unfortunately, the short time available to perform detailed and thorough due diligence checks, force us reluctantly to abandon this idea and challenge.”


title: Andrea Radrizzani

text: On 31 July, Radrizzani signed striker Patrick Bamford to Leeds for £7 million (rising up to £10 million), the move representing the highest fee Leeds had spent on a player since Robbie Fowler's move to the club in 2001.


title: Andrea Radrizzani

text: After the sale of promising young player Ronaldo Vieira to Italian side Sampdoria on 1 August, Radrizzani defended the sale to supporters by saying “We cannot buy players and never sell players.”


title: Andrea Radrizzani

text: During the 2018–19 Leeds United F.C. season, Leeds finished the regular season in third place after dropping out of the automatic promotion places with three games left after a defeat to ten-man Wigan Athletic on 19 April, Leeds qualified for the playoffs versus sixth-placed Derby County, winning the first leg of the playoffs 1–0 win at Pride Park, but lost the home leg 2–4 with Leeds also down to ten men after the dismissal of Gaetano Berardi. The loss saw Derby progress 4–3 on aggregate to the final against Aston Villa and Radrizzani's club narrowly miss out on promotion.


title: Andrea Radrizzani

text: In August 2019, Radrizzani was one of the main participants in the Leeds United documentary 'Take Us Home' documenting the 2018–19 season on Amazon Prime, featuring in all episodes. The documentary was narrated by Academy Award-winning actor and Leeds United fan Russell Crowe.


title: Andrea Radrizzani

text: On 23 September 2019, Radrizzani was present at The Best FIFA Football Awards 2019 as Leeds Head Coach Marcelo Bielsa and the entire Leeds United squad won the FIFA Fair Play Award: 2019 for Bielsa's sportsmanship in May 2019 to allow Aston Villa to score a goal unopposed in a game in which the ultimate result ended Leeds' 'mathematical' chances of automatic promotion the prior season.


title: Andrea Radrizzani

text: Leeds United's 2019/20 Championship season began with a 3–1 victory over Bristol City on 4 August 2019. The aim for the season was promotion and the club started well, with 13 points from the first five matches.


title: Andrea Radrizzani

text: Leeds were a leading team throughout the 2019/20 season and never fell below fifth place in the table. The team’s largest victory of the campaign was a 5–0 victory over Stoke City on 9 July 2020. On 17 July 2020, Leeds United were assured of promotion to the Premier League, returning to the top flight after 16 years. On 22 July 2020, Leeds finished the season with a 4–0 victory over Charlton Athletic, before lifting the Sky Bet Championship trophy at Elland Road. Leeds amassed 93 points during the Championship season, with 28 wins and 77 goals scored. Ultimately, the club was crowned champions after finishing the season 10 points clear of second-placed West Bromwich Albion.


title: Andrea Radrizzani

text: On 8 July 2020, Leeds United's Academy was awarded Category One status by the Premier League due to the club's commitment to developing young players. It is the first time in Leeds’ history that the Academy has reached Category One status.


title: Andrea Radrizzani

text: Radrizzani has invested in a number of additional sports, media and entertainment companies with Aser, including Italian based digital media network Hellodì, San Francisco-based technology startup Sports Data Labs, the football news app One Football, the digital entertainment brand Epico, the sports agency Base, OTRO and the production company Easyprod.


title: Andrea Radrizzani

text: Radrizzani is also founder and chairman of the Play for Change Foundation, a charity that runs sport and education programmes for children both internationally and in Italy, his home country.


title: PRINCE2

text: PRINCE2 (PRojects IN Controlled Environments) is a structured project management method and practitioner certification programme. PRINCE2 emphasises dividing projects into manageable and controllable stages.


title: PRINCE2

text: It is adopted in many countries worldwide, including the UK, Western European countries, and Australia.


title: PRINCE2

text: PRINCE2 was developed as a UK government standard for information systems projects. In July 2013, ownership of the rights to PRINCE2 were transferred from HM Cabinet Office to AXELOS Ltd, a joint venture by the Cabinet Office and Capita, with 49% and 51% stakes respectively.


title: PRINCE2

text: PRINCE was derived from an earlier method called PROMPT II (Project Resource Organisation Management Planning Techniques). In 1989 the Central Computer and Telecommunications Agency (CCTA) adopted a version of PROMPT II as a UK Government standard for information systems (IT) project management. They gave it the name 'PRINCE', which originally stood for "PROMPT II IN the CCTA Environment". PRINCE was renamed in a civil service competition as an acronym for "PRojects IN Controlled Environments". PRINCE2 is the second edition of the earlier PRINCE method which was initially announced and developed in 1989 by the Central Computer and Telecommunications Agency (CCTA), a UK government support agency. PRINCE2 was released in 1996 as a generic project management method. PRINCE2 has become increasingly popular and is now a "de facto" standard for project management in many UK government departments and across the United Nations system. There have been two major revisions of PRINCE2 since its launch in 1996: "PRINCE2:2009 Refresh" in 2009, and "PRINCE2 2017 Update" in 2017. The justification for the 2017 update was the evolution in practical business practices and feedback from PRINCE2 practitioners in the actual project environment.


title: PRINCE2

text: These aspects are also called tolerances or performance goals. They quantify the project tolerance and are considered during decision-making processes. In some organisations these can be key performance indicators (KPIs). In the following table project level tolerances are summarised:


title: PRINCE2

text: Benefits can have as target the cost of the benefit, but the cost tolerance above is related to the cost of the project, not the cost of the benefit.


title: PRINCE2

text: PRINCE2 is based on seven principles and these cannot be tailored. The PRINCE2 principles can be described as a mindset that keeps the project aligned with the PRINCE2 methodology. If a project does not adhere to these principles, it is not being managed using PRINCE2.


title: PRINCE2

text: Not every aspect of PRINCE2 will be applicable to every project, thus every process has a note on scalability. This provides guidance to the project manager (and others involved in the project) as to "how much" of the process to apply. The positive aspect of this is that PRINCE2 can be tailored to the needs of a particular project. The negative aspect is that many of the essential elements of PRINCE2 can be omitted sometimes resulting in a PINO project – PRINCE in Name Only


title: PRINCE2

text: The PRINCE2 manual contains 26 suggested templates for documentation associated with the project, which it terms "management products" and which are divided into "baselines", "records" and "reports". Some examples of management products are:


title: PRINCE2

text: The 26 Management Products described by PRINCE2 are only used for the "high-level" management of the project. Within its tasks, task managers must still decide on their own project management framework.


title: PRINCE2

text: Some suggestions given in the PRINCE2 manual are product based planning, change control, quality review technique, Gantt charts, PERT charts and critical path analysis.


title: PRINCE2

text: The quality review technique ensures a project's products are of the required standard (i.e. meet defined quality criteria). This takes place in a quality review meeting, which identifies errors in the product. The quality review meeting will not attempt to solve the problems it identifies. The meeting brings together people who have an interest in the project's outputs (or products) and people on the project team able to address issues identified.


title: PRINCE2

text: Below is a list of all the editions of PRINCE2. As of 1 January 2020, "PRINCE2 2017" was renamed "PRINCE2 6th Edition". Also, the previous edition, "PRINCE2 2009" was renamed "PRINCE2 5th Edition". There were no other changes except the name of the brand. The reason for the name change was to "ensure the format of the name is aligned with that used by other frameworks within the project management industry". As list of all versions of PRINCE2 are printed in the cover of the PRINCE2 manual:


title: PRINCE2

text: PRINCE2 Agile is a tailored form of PRINCE2, suitable for Agile projects that use Scrum, Kanban, or a similar Agile system in their delivery layer. It adds a management and governance layer on top of the relatively simple Agile methods that are focused on the delivery layer.


title: PRINCE2

text: PRINCE2 Agile was released in 2015 and are intended for those who work in development projects, while PRINCE2 AgileSHIFT from 2018 are intended for bringing the agile mindset to the other parts of an organisation than those who work directly on projects. Like the regular PRINCE2, both are available on the Foundation and Practitioner levels.


title: PRINCE2

text: PRINCE2 certifications, awarded by AXELOS, require the user to undertake a training course with an Accredited Training Organisation (ATO) followed by an exam. The training and exam may be online or in person. AXELOS requires that any organisation providing official PRINCE2 training must go through an accreditation process in order to validate the quality of the course content and delivery. Once approved, the organisation can use the title "Accredited Training Organisation" (ATO). Trainers must be re-accredited every 3 years and undergo a surveillance check every 12 months.


title: PRINCE2

text: The PRINCE2 certification is recognised globally for its practice- driven approach to project management. AXELOS publishes a successful candidate register which can be searched on the web. In the PRINCE2 certification, there are different level that are necessary for the application to pass for becoming certified PRINCE2 professional.


title: PRINCE2

text: PRINCE2 provides a method for managing projects within a clearly defined framework, but project management is a complex discipline and using such a framework is no guarantee of a successful project.


title: PRINCE2

text: Some of the advertised benefits of PRINCE2 are: increased quality of the finished products, efficient control of resources, avoidance of either "heroic" (under-regulated) or "mechanistic" (over-regulated) working, and increased confidence among the project team.


title: PRINCE2

text: PRINCE2 is sometimes considered inappropriate for small projects or where requirements are expected to change, due to the work required in creating and maintaining documents, logs and lists. The deliverable structure may also lead to focus on producing deliverables for their own sake, to "tick the boxes" rather than do more useful work.


title: PRINCE2

text: The general response of PRINCE2's authors to criticism has been to point out that the methodology is scalable and can be tailored to suit the specific requirements and constraints of the project and the environment. This strong emphasis on tailoring has led some users to complain that PRINCE2 is unfalsifiable, i.e. it is impossible to tell whether PRINCE2 "works" or constitutes "best practice" if any problems encountered with a project can be blamed on inappropriate application of PRINCE2 rather than on PRINCE2 itself.


title: PRINCE2

text: The experiences of the Blair administration in the UK between 1997 and 2007 (and of subsequent UK governments) arguably undermine PRINCE2's claim to be "best practice", given the string of high-profile failed IT projects charged to the taxpayer during that time, and the controversy surrounding the financial relationship between the Blair government and PRINCE2's co-owners Capita. PRINCE2's training material addresses these failures, blaming them on inappropriate tailoring of PRINCE2 to the project environment, and advocating for more PRINCE2 training for government project managers to solve the problem.


title: PRINCE2

text: Project Management Professional (PMP) from Project Management Institute may be seen as a competitor of PRINCE2. In general, the UK, Australia prefer PRINCE2, and the US and American countries prefer PMP. Asia, Africa and the Middle East area have no strong preference for PMP or PRINCE2.


title: PRINCE2

text: PRINCE2 and PMP acknowledge each other's existence in their advertising material and attempt to position themselves as complementary products – PRINCE2 as a "methodology" and PMP as a "standard" – which can be used alongside each other. In practice, companies and practitioners choose one system or both depending on the project environment, their geographical location and costs involved.


title: Reiko Aylesworth

text: Reiko M. Aylesworth (born December 9, 1972) is an American film, television and stage actress, best known for her role on the television series "24" as Michelle Dessler.


title: Reiko Aylesworth

text: Aylesworth was born December 9, 1972, in Evanston, Illinois, and is of Dutch, Welsh, and Japanese ancestry. Her given name "Reiko" (礼子) is Japanese; her surname Aylesworth is English. She lived in Springfield, Illinois, from 1987 to 1988, where she first became interested in acting. After understudying in several productions at the Springfield Theatre Centre, Aylesworth was cast in the role of Consuelo in "West Side Story", while her family was preparing to move to Seattle, Washington. When her family left for Seattle, she remained in Springfield with family friends for the duration of the play's run.


title: Reiko Aylesworth

text: After joining her family in Seattle, Aylesworth attended the University of Washington and studied neuroscience. While there, Aylesworth participated in several local theatre productions including "Invisible Friends" at the Seattle Children's Theatre and the Intiman Theatre Company's production of Peter Pan where she played Wendy.


title: Reiko Aylesworth

text: Aylesworth's performance in "Peter Pan" brought her to the attention of talent scouts at ABC, leading to the beginning of her television and film career as Rebecca Lewis on the soap opera "One Life to Live". After her character was written out of "One Life to Live", she appeared in the independent film "Childhood's End" and the final episode of the HBO series "". During this time Aylesworth also appeared in at least three Off Broadway productions.


title: Reiko Aylesworth

text: Following a guest appearance on "Law & Order" and a supporting role in the miniseries "A Will of Their Own", Aylesworth had minor appearances in the movies "Random Hearts" and "You've Got Mail" followed by a guest star role in the CBS series "Now and Again". Soon after NBC cast Aylesworth as Becca Coltrane in the pilot for the series "Sherman's March," however, it was not picked up and aired as a standalone television movie.


title: Reiko Aylesworth

text: Aylesworth continued her work on television with guest appearances in "The West Wing", "", and "Ed" as well as being cast in a lead role in the supernatural hospital drama "All Souls". When "All Souls" was cancelled after its sixth episode, Aylesworth joined the cast of the new series "The American Embassy", which was quickly cancelled after its fourth episode.


title: Reiko Aylesworth

text: Following the cancellation of "The American Embassy", Aylesworth auditioned for the part of Nina Myers on Fox Network's "24" but the role went to Sarah Clarke. When casting began for 24's second season, Aylesworth again auditioned, this time for the part of Kate Warner, but the role went to Sarah Wynter. However, the producers were impressed with her and asked her to join the cast for a ten episode recurring role as Michelle Dessler, a CTU agent. Despite being credited as a guest star for the entire season, she appeared in all 24 episodes.


title: Reiko Aylesworth

text: Director Jon Cassar quickly noticed the "chemistry" between Aylesworth and her costar Carlos Bernard, in the role of Tony Almeida. which led to a decision to develop the characters' onscreen relationship. The relationship between Michelle and Tony quickly became popular with fans and later would resurface as one of the driving forces in "24"'s seventh season.


title: Reiko Aylesworth

text: While on hiatus from "24" after season two, Aylesworth filmed an episode for the second season of "The Dead Zone", playing a love interest for Anthony Michael Hall's Johnny Smith. By 24's third season (2003–2004), Aylesworth had become a main cast member with Tony and Michelle now married and holding leadership positions at CTU. However, when the season concluded, the writers announced that most of the characters were being dropped, with those actors not being retained for season 4. Upon being released from "24", Aylesworth was cast as Chandra Moore, a DNA analyst, in the fifth season of ""; while the role was intended to be recurring, it was dropped after the September 2004 season opener.


title: Reiko Aylesworth

text: As season 4 of "24" progressed, some of the characters from previous seasons returned mid-season, including Aylesworth as Michelle Dessler. The character returns in the twelfth episode, now a high level bureaucrat within the CTU hierarchy, serving as CTU Director for the remainder of the season. Her character resigns at the end in order to remarry Tony Almeida, then is killed by a car bomb in the opening episode of season 5.


title: Reiko Aylesworth

text: Following her departure from "24," Aylesworth has remained active in both television and movies as well as theatre. Her first leading role in a feature film was in the independent, romantic drama "Crazy love" where she worked alongside Bruno Campos and former "24" costar Paul Schulze. "Crazylove" tells the story of Letty Mayer, a school teacher who suffers a nervous breakdown and while institutionalized, meets Michael (Campos) and the two begin a dangerous and unpredictable romance. She partnered with her former "24" costar Xander Berkeley in the Sci Fi Channel made-for-television movie, . In a guest start role on the short-lived series "Conviction", she played a renowned attorney who killed her husband and then defended herself at the murder trial. When the cast was selected for the series 3 lbs, Aylesworth was chosen for the role of Dr. Adrienne Holland, but the pilot was rejected by CBS. The following season, CBS decided to buy the series for a late fall 2006 premiere, but the lead roles were recast, including Aylesworth's. It is unknown whether she declined the "3 lbs" role or she was not offered it again.


title: Reiko Aylesworth

text: Soon after the conclusion of 24's fifth season, Aylesworth and her "24" costar D. B. Woodside filmed the short, "First" which was also written, produced, and directed by Woodside. Aylesworth's character, Angelina Marveau, was "a fallen French nun" who was fighting to choose between her religious beliefs and first love, a nihilistic, American professor, who was portrayed by Woodside.


title: Reiko Aylesworth

text: In 2006, Aylesworth filmed roles for two feature movie along with an independent production. In the Kevin Costner movie, "Mr. Brooks," Aylesworth portrayed a divorce lawyer, Sheila, who was representing the husband of Demi Moore's character, Detective Tracy Atwood. Departing from her previous type of characters, Aylesworth played the femme fatale Audrey Levine in the Gideon Raff independent thriller "The Killing Floor".


title: Reiko Aylesworth

text: Aylesworth played one of the two lead roles in "" (2007). Her character, Kelly O'Brien, an Army pilot and soldier returning home after being deployed overseas, arrives in Gunnison, Colorado the day before the Aliens and Predator invade the town.


title: Reiko Aylesworth

text: In January 2007, Aylesworth had a guest role in two episodes of the ABC comedy, "The Knights of Prosperity", where she played the head of Mick Jagger's security company, Simone Cashwell. The Knights attempt to seduce her character in order to obtain the necessary security codes to access Mick Jagger's apartment and later trick Simone in order to get her thumbprint which is also needed to open the door. Soon after she filmed a supporting role in Hannah Davis and David Conolly's "The Understudy" where she played Police Chief Kinsky. While it has appeared at numerous film festivals, a DVD release date for "The Understudy" has not been announced.


title: Reiko Aylesworth

text: Aylesworth continued her work in independent productions, filming a small part for Steven Kampmann's independent movie, "Buzzkill". It was given a limited release in January 2012. In April 2008, Aylesworth was cast in a recurring role on "ER", playing hospital chaplain Julia Dupree. Originally, Dupree was to appear in 5 episodes with the purpose of attracting the lecherous attention of Dr. Gates (John Stamos). Her role was extended for two additional episodes, but concluded due to the suspension of filming resulting from the 2007-2008 WGA Strike. A month later Aylesworth filmed a supporting role in the Steve Morris independent comedy "The Assistants", which tells the story of a group of Hollywood assistants who are scheming to have their script turned into a feature film. Aylesworth has often said independent productions like these and past films such as "No Deposit, No Return", are her preferred types of film.


title: Reiko Aylesworth

text: Aylesworth has continued with one-off guest roles on episodes of various television dramas. She has also appeared in recurring roles, including five episodes in season three of Damages, as Dr. Malia Waincroft on seven episodes over three seasons of CBS's "Hawaii Five-0", and nine episodes as Allie Jones over two seasons of "Scorpion" in 2016 and 2017.


title: Reiko Aylesworth

text: Aylesworth has appeared in off-Broadway productions. She performed in the 2006 production of Etan Frankel's "The Fearless" at the Summer Play Festival and The New Group (naked)'s 2007 production of Heather Lynn MacDonald's "Expats".


title: Reiko Aylesworth

text: , Aylesworth had resided in New York City since 1993. Aylesworth is married to Rob Clare, a scholar and expert on Shakespearean theatre.


title: Alison Owen

text: Alison Mary Owen (born 18 February 1961) is an English film producer. Her credits as a producer include "Moonlight and Valentino" (1995), "Elizabeth" (1998), "Sylvia" (2003), "Shaun of the Dead" (2004), "Proof" (2005), "The Other Boleyn Girl" (2007), "Brick Lane" (2007), "Chatroom" (2010), "Saving Mr. Banks" (2013), "Tulip Fever" (2017).


title: Alison Owen

text: Owen was born in Portsmouth, Hampshire, into a Roman Catholic family. Her parents were Mary Kathleen (née Hitchiner), a Royal Navy dockyard worker, and Peter Ronald Owen, chief petty officer in the Royal Navy, and was the younger of two daughters. Her sister is Jill Beatrice Owen (born 1959).


title: Alison Owen

text: Owen's first marriage (other sources simply say "relationship") started when she was a teenager in the 1970s, producing her first child, Sarah, in late December 1979, when Owen was an 18-year-old university student. She married actor Keith Allen in 1984, and they had two children together, pop singer Lily Allen and actor Alfie Allen, before divorcing in 1989. She also had a relationship with comedian Harry Enfield who was a common-law stepfather to Owen's children. She is currently married to art director Aaron Batterham, who has four children of his own.


title: Alison Owen

text: In 2017, the National Portrait Gallery acquired an early portrait of Owen for their permanent collection by photographer David Gwinnutt.


title: Alison Owen

text: She first started working at Limelight doing music videos. Later she then produced her first movie "Hear My Song" and a TV series called "Diary of a Teenage Health Freak". Then she worked for Working Title. She set up the low-budget film division. Her production company is Ruby Films.


title: Amanda Leighton

text: Amanda Leighton is an American actress. She is known for her voice acting as Blossom in the 2016 Cartoon Network animated series "The Powerpuff Girls", Poppy in the 2018 Netflix animated series "", and Polly Plantar in the 2019 Disney Channel animated series "Amphibia". She is also known for her recurring role as Emma in the Freeform drama series "The Fosters".


title: Amanda Leighton

text: Leighton started her acting career at the age of 10 in her home town, and got her first agent at the age of 12 when she started taking acting classes and going to auditions in Los Angeles. She also has 11 years of dance experience, which she used in ABC Family's "Make It or Break It", where she played a gymnast named Wendy Capshaw.


title: Amanda Leighton

text: Leighton's other appearances include roles on several television shows including "Pretty Little Liars" as Danielle, "Grey's Anatomy" as patient Sarah Cassidy with Treacher Collins syndrome, "90210" as Alex Scarborough, "Criminal Minds" as Trish Leake, "This is Us" as teenage Sophie, "The Fosters" as Emma, and as a singing Cactus Kid in "Six Feet Under". She has appeared in commercials for Quicken Loans, Meow Mix, Comcast, and Plavix. Leighton had parts in two films: "Detour" as Lara (short film), and as Young Alex in "Divorce Invitation" (2012).


title: DNA repair

text: DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA damage, resulting in tens of thousands of individual molecular lesions per cell per day. Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes. Other lesions induce potentially harmful mutations in the cell's genome, which affect the survival of its daughter cells after it undergoes mitosis. As a consequence, the DNA repair process is constantly active as it responds to damage in the DNA structure. When normal repair processes fail, and when cellular apoptosis does not occur, irreparable DNA damage may occur, including double-strand breaks and DNA crosslinkages (interstrand crosslinks or ICLs). This can eventually lead to malignant tumors, or cancer as per the two hit hypothesis.


title: DNA repair

text: The rate of DNA repair is dependent on many factors, including the cell type, the age of the cell, and the extracellular environment. A cell that has accumulated a large amount of DNA damage, or one that no longer effectively repairs damage incurred to its DNA, can enter one of three possible states:


title: DNA repair

text: The DNA repair ability of a cell is vital to the integrity of its genome and thus to the normal functionality of that organism. Many genes that were initially shown to influence life span have turned out to be involved in DNA damage repair and protection.


title: DNA repair

text: The 2015 Nobel Prize in Chemistry was awarded to Tomas Lindahl, Paul Modrich, and Aziz Sancar for their work on the molecular mechanisms of DNA repair processes.


title: DNA repair

text: DNA damage, due to environmental factors and normal metabolic processes inside the cell, occurs at a rate of 10,000 to 1,000,000 molecular lesions per cell per day. While this constitutes only 0.000165% of the human genome's approximately 6 billion bases, unrepaired lesions in critical genes (such as tumor suppressor genes) can impede a cell's ability to carry out its function and appreciably increase the likelihood of tumor formation and contribute to tumour heterogeneity.


title: DNA repair

text: The vast majority of DNA damage affects the primary structure of the double helix; that is, the bases themselves are chemically modified. These modifications can in turn disrupt the molecules' regular helical structure by introducing non-native chemical bonds or bulky adducts that do not fit in the standard double helix. Unlike proteins and RNA, DNA usually lacks tertiary structure and therefore damage or disturbance does not occur at that level. DNA is, however, supercoiled and wound around "packaging" proteins called histones (in eukaryotes), and both superstructures are vulnerable to the effects of DNA damage.


title: DNA repair

text: The replication of damaged DNA before cell division can lead to the incorporation of wrong bases opposite damaged ones. Daughter cells that inherit these wrong bases carry mutations from which the original DNA sequence is unrecoverable (except in the rare case of a back mutation, for example, through gene conversion).


title: DNA repair

text: UV damage, alkylation/methylation, X-ray damage and oxidative damage are examples of induced damage. Spontaneous damage can include the loss of a base, deamination, sugar ring puckering and tautomeric shift. Constitutive (spontaneous) DNA damage caused by endogenous oxidants can be detected as a low level of histone H2AX phosphorylation in untreated cells.


title: DNA repair

text: In human cells, and eukaryotic cells in general, DNA is found in two cellular locations – inside the nucleus and inside the mitochondria. Nuclear DNA (nDNA) exists as chromatin during non-replicative stages of the cell cycle and is condensed into aggregate structures known as chromosomes during cell division. In either state the DNA is highly compacted and wound up around bead-like proteins called histones. Whenever a cell needs to express the genetic information encoded in its nDNA the required chromosomal region is unravelled, genes located therein are expressed, and then the region is condensed back to its resting conformation. Mitochondrial DNA (mtDNA) is located inside mitochondria organelles, exists in multiple copies, and is also tightly associated with a number of proteins to form a complex known as the nucleoid. Inside mitochondria, reactive oxygen species (ROS), or free radicals, byproducts of the constant production of adenosine triphosphate (ATP) via oxidative phosphorylation, create a highly oxidative environment that is known to damage mtDNA. A critical enzyme in counteracting the toxicity of these species is superoxide dismutase, which is present in both the mitochondria and cytoplasm of eukaryotic cells.


title: DNA repair

text: Senescence, an irreversible process in which the cell no longer divides, is a protective response to the shortening of the chromosome ends, called telomeres. The telomeres are long regions of repetitive noncoding DNA that cap chromosomes and undergo partial degradation each time a cell undergoes division (see Hayflick limit). In contrast, quiescence is a reversible state of cellular dormancy that is unrelated to genome damage (see cell cycle). Senescence in cells may serve as a functional alternative to apoptosis in cases where the physical presence of a cell for spatial reasons is required by the organism, which serves as a "last resort" mechanism to prevent a cell with damaged DNA from replicating inappropriately in the absence of pro-growth cellular signaling. Unregulated cell division can lead to the formation of a tumor (see cancer), which is potentially lethal to an organism. Therefore, the induction of senescence and apoptosis is considered to be part of a strategy of protection against cancer.


title: DNA repair

text: It is important to distinguish between DNA damage and mutation, the two major types of error in DNA. DNA damage and mutation are fundamentally different. Damage results in physical abnormalities in the DNA, such as single- and double-strand breaks, 8-hydroxydeoxyguanosine residues, and polycyclic aromatic hydrocarbon adducts. DNA damage can be recognized by enzymes, and thus can be correctly repaired if redundant information, such as the undamaged sequence in the complementary DNA strand or in a homologous chromosome, is available for copying. If a cell retains DNA damage, transcription of a gene can be prevented, and thus translation into a protein will also be blocked. Replication may also be blocked or the cell may die.


title: DNA repair

text: In contrast to DNA damage, a mutation is a change in the base sequence of the DNA. A mutation cannot be recognized by enzymes once the base change is present in both DNA strands, and thus a mutation cannot be repaired. At the cellular level, mutations can cause alterations in protein function and regulation. Mutations are replicated when the cell replicates. In a population of cells, mutant cells will increase or decrease in frequency according to the effects of the mutation on the ability of the cell to survive and reproduce.


title: DNA repair

text: Although distinctly different from each other, DNA damage and mutation are related because DNA damage often causes errors of DNA synthesis during replication or repair; these errors are a major source of mutation.


title: DNA repair

text: Given these properties of DNA damage and mutation, it can be seen that DNA damage is a special problem in non-dividing or slowly-dividing cells, where unrepaired damage will tend to accumulate over time. On the other hand, in rapidly dividing cells, unrepaired DNA damage that does not kill the cell by blocking replication will tend to cause replication errors and thus mutation. The great majority of mutations that are not neutral in their effect are deleterious to a cell's survival. Thus, in a population of cells composing a tissue with replicating cells, mutant cells will tend to be lost. However, infrequent mutations that provide a survival advantage will tend to clonally expand at the expense of neighboring cells in the tissue. This advantage to the cell is disadvantageous to the whole organism because such mutant cells can give rise to cancer. Thus, DNA damage in frequently dividing cells, because it gives rise to mutations, is a prominent cause of cancer. In contrast, DNA damage in infrequently-dividing cells is likely a prominent cause of aging.


title: DNA repair

text: Cells cannot function if DNA damage corrupts the integrity and accessibility of essential information in the genome (but cells remain superficially functional when non-essential genes are missing or damaged). Depending on the type of damage inflicted on the DNA's double helical structure, a variety of repair strategies have evolved to restore lost information. If possible, cells use the unmodified complementary strand of the DNA or the sister chromatid as a template to recover the original information. Without access to a template, cells use an error-prone recovery mechanism known as translesion synthesis as a last resort.


title: DNA repair

text: Damage to DNA alters the spatial configuration of the helix, and such alterations can be detected by the cell. Once damage is localized, specific DNA repair molecules bind at or near the site of damage, inducing other molecules to bind and form a complex that enables the actual repair to take place.


title: DNA repair

text: Cells are known to eliminate three types of damage to their DNA by chemically reversing it. These mechanisms do not require a template, since the types of damage they counteract can occur in only one of the four bases. Such direct reversal mechanisms are specific to the type of damage incurred and do not involve breakage of the phosphodiester backbone. The formation of pyrimidine dimers upon irradiation with UV light results in an abnormal covalent bond between adjacent pyrimidine bases. The photoreactivation process directly reverses this damage by the action of the enzyme photolyase, whose activation is obligately dependent on energy absorbed from blue/UV light (300–500 nm wavelength) to promote catalysis. Photolyase, an old enzyme present in bacteria, fungi, and most animals no longer functions in humans, who instead use nucleotide excision repair to repair damage from UV irradiation. Another type of damage, methylation of guanine bases, is directly reversed by the protein methyl guanine methyl transferase (MGMT), the bacterial equivalent of which is called ogt. This is an expensive process because each MGMT molecule can be used only once; that is, the reaction is stoichiometric rather than catalytic. A generalized response to methylating agents in bacteria is known as the adaptive response and confers a level of resistance to alkylating agents upon sustained exposure by upregulation of alkylation repair enzymes. The third type of DNA damage reversed by cells is certain methylation of the bases cytosine and adenine.


title: DNA repair

text: When only one of the two strands of a double helix has a defect, the other strand can be used as a template to guide the correction of the damaged strand. In order to repair damage to one of the two paired molecules of DNA, there exist a number of excision repair mechanisms that remove the damaged nucleotide and replace it with an undamaged nucleotide complementary to that found in the undamaged DNA strand.


title: DNA repair

text: Double-strand breaks, in which both strands in the double helix are severed, are particularly hazardous to the cell because they can lead to genome rearrangements. In fact, when a double-strand break is accompanied by a cross-linkage joining the two strands at the same point, neither strand can be used as a template for the repair mechanisms, so that the cell will not be able to complete mitosis when it next divides, and will either die or, in rare cases, undergo a mutation. Three mechanisms exist to repair double-strand breaks (DSBs): non-homologous end joining (NHEJ), microhomology-mediated end joining (MMEJ), and homologous recombination (HR):


title: DNA repair

text: In an "in vitro" system, MMEJ occurred in mammalian cells at the levels of 10–20% of HR when both HR and NHEJ mechanisms were also available.


title: DNA repair

text: The extremophile "Deinococcus radiodurans" has a remarkable ability to survive DNA damage from ionizing radiation and other sources. At least two copies of the genome, with random DNA breaks, can form DNA fragments through annealing. Partially overlapping fragments are then used for synthesis of homologous regions through a moving D-loop that can continue extension until complementary partner strands are found. In the final step, there is crossover by means of RecA-dependent homologous recombination.


title: DNA repair

text: Topoisomerases introduce both single- and double-strand breaks in the course of changing the DNA's state of supercoiling, which is especially common in regions near an open replication fork. Such breaks are not considered DNA damage because they are a natural intermediate in the topoisomerase biochemical mechanism and are immediately repaired by the enzymes that created them.


title: DNA repair

text: Another type of DNA double-strand breaks originates from the DNA heat-sensitive or heat-labile sites. These DNA sites are not initial DSBs. However, they convert to DSB after treating with elevated temperature. Ionizing irradiation can induces a highly complex form of DNA damage as clustered damage. It consists of different types of DNA lesions in various locations of the DNA helix. Some of these closely located lesions can probably convert to DSB by exposure to high temperatures. But the exact nature of these lesions and their interactions is not yet known


title: DNA repair

text: Translesion synthesis (TLS) is a DNA damage tolerance process that allows the DNA replication machinery to replicate past DNA lesions such as thymine dimers or AP sites. It involves switching out regular DNA polymerases for specialized translesion polymerases (i.e. DNA polymerase IV or V, from the Y Polymerase family), often with larger active sites that can facilitate the insertion of bases opposite damaged nucleotides. The polymerase switching is thought to be mediated by, among other factors, the post-translational modification of the replication processivity factor PCNA. Translesion synthesis polymerases often have low fidelity (high propensity to insert wrong bases) on undamaged templates relative to regular polymerases. However, many are extremely efficient at inserting correct bases opposite specific types of damage. For example, Pol η mediates error-free bypass of lesions induced by UV irradiation, whereas Pol ι introduces mutations at these sites. Pol η is known to add the first adenine across the T^T photodimer using Watson-Crick base pairing and the second adenine will be added in its syn conformation using Hoogsteen base pairing. From a cellular perspective, risking the introduction of point mutations during translesion synthesis may be preferable to resorting to more drastic mechanisms of DNA repair, which may cause gross chromosomal aberrations or cell death. In short, the process involves specialized polymerases either bypassing or repairing lesions at locations of stalled DNA replication. For example, Human DNA polymerase eta can bypass complex DNA lesions like guanine-thymine intra-strand crosslink, G[8,5-Me]T, although it can cause targeted and semi-targeted mutations. Paromita Raychaudhury and Ashis Basu studied the toxicity and mutagenesis of the same lesion in "Escherichia coli" by replicating a G[8,5-Me]T-modified plasmid in "E. coli" with specific DNA polymerase knockouts. Viability was very low in a strain lacking pol II, pol IV, and pol V, the three SOS-inducible DNA polymerases, indicating that translesion synthesis is conducted primarily by these specialized DNA polymerases.


title: DNA repair

text: A bypass platform is provided to these polymerases by Proliferating cell nuclear antigen (PCNA). Under normal circumstances, PCNA bound to polymerases replicates the DNA. At a site of lesion, PCNA is ubiquitinated, or modified, by the RAD6/RAD18 proteins to provide a platform for the specialized polymerases to bypass the lesion and resume DNA replication. After translesion synthesis, extension is required. This extension can be carried out by a replicative polymerase if the TLS is error-free, as in the case of Pol η, yet if TLS results in a mismatch, a specialized polymerase is needed to extend it; Pol ζ. Pol ζ is unique in that it can extend terminal mismatches, whereas more processive polymerases cannot. So when a lesion is encountered, the replication fork will stall, PCNA will switch from a processive polymerase to a TLS polymerase such as Pol ι to fix the lesion, then PCNA may switch to Pol ζ to extend the mismatch, and last PCNA will switch to the processive polymerase to continue replication.


title: DNA repair

text: Cells exposed to ionizing radiation, ultraviolet light or chemicals are prone to acquire multiple sites of bulky DNA lesions and double-strand breaks. Moreover, DNA damaging agents can damage other biomolecules such as proteins, carbohydrates, lipids, and RNA. The accumulation of damage, to be specific, double-strand breaks or adducts stalling the replication forks, are among known stimulation signals for a global response to DNA damage. The global response to damage is an act directed toward the cells' own preservation and triggers multiple pathways of macromolecular repair, lesion bypass, tolerance, or apoptosis. The common features of global response are induction of multiple genes, cell cycle arrest, and inhibition of cell division.


title: DNA repair

text: The packaging of eukaryotic DNA into chromatin presents a barrier to all DNA-based processes that require recruitment of enzymes to their sites of action. To allow DNA repair, the chromatin must be remodeled. In eukaryotes, ATP dependent chromatin remodeling complexes and histone-modifying enzymes are two predominant factors employed to accomplish this remodeling process.


title: DNA repair

text: Chromatin relaxation occurs rapidly at the site of a DNA damage. In one of the earliest steps, the stress-activated protein kinase, c-Jun N-terminal kinase (JNK), phosphorylates SIRT6 on serine 10 in response to double-strand breaks or other DNA damage. This post-translational modification facilitates the mobilization of SIRT6 to DNA damage sites, and is required for efficient recruitment of poly (ADP-ribose) polymerase 1 (PARP1) to DNA break sites and for efficient repair of DSBs. PARP1 protein starts to appear at DNA damage sites in less than a second, with half maximum accumulation within 1.6 seconds after the damage occurs. PARP1 synthesizes polymeric adenosine diphosphate ribose (poly (ADP-ribose) or PAR) chains on itself. Next the chromatin remodeler ALC1 quickly attaches to the product of PARP1 action, a poly-ADP ribose chain, and ALC1 completes arrival at the DNA damage within 10 seconds of the occurrence of the damage. About half of the maximum chromatin relaxation, presumably due to action of ALC1, occurs by 10 seconds. This then allows recruitment of the DNA repair enzyme MRE11, to initiate DNA repair, within 13 seconds.


title: DNA repair

text: γH2AX, the phosphorylated form of H2AX is also involved in the early steps leading to chromatin decondensation after DNA double-strand breaks. The histone variant H2AX constitutes about 10% of the H2A histones in human chromatin. γH2AX (H2AX phosphorylated on serine 139) can be detected as soon as 20 seconds after irradiation of cells (with DNA double-strand break formation), and half maximum accumulation of γH2AX occurs in one minute. The extent of chromatin with phosphorylated γH2AX is about two million base pairs at the site of a DNA double-strand break. γH2AX does not, itself, cause chromatin decondensation, but within 30 seconds of irradiation, RNF8 protein can be detected in association with γH2AX. RNF8 mediates extensive chromatin decondensation, through its subsequent interaction with CHD4, a component of the nucleosome remodeling and deacetylase complex NuRD.


title: DNA repair

text: DDB2 occurs in a heterodimeric complex with DDB1. This complex further complexes with the ubiquitin ligase protein CUL4A and with PARP1. This larger complex rapidly associates with UV-induced damage within chromatin, with half-maximum association completed in 40 seconds. The PARP1 protein, attached to both DDB1 and DDB2, then PARylates (creates a poly-ADP ribose chain) on DDB2 that attracts the DNA remodeling protein ALC1. Action of ALC1 relaxes the chromatin at the site of UV damage to DNA. This relaxation allows other proteins in the nucleotide excision repair pathway to enter the chromatin and repair UV-induced cyclobutane pyrimidine dimer damages.


title: DNA repair

text: After rapid chromatin remodeling, cell cycle checkpoints are activated to allow DNA repair to occur before the cell cycle progresses. First, two kinases, ATM and ATR are activated within 5 or 6 minutes after DNA is damaged. This is followed by phosphorylation of the cell cycle checkpoint protein Chk1, initiating its function, about 10 minutes after DNA is damaged.


title: DNA repair

text: After DNA damage, cell cycle checkpoints are activated. Checkpoint activation pauses the cell cycle and gives the cell time to repair the damage before continuing to divide. DNA damage checkpoints occur at the G1/S and G2/M boundaries. An intra-S checkpoint also exists. Checkpoint activation is controlled by two master kinases, ATM and ATR. ATM responds to DNA double-strand breaks and disruptions in chromatin structure, whereas ATR primarily responds to stalled replication forks. These kinases phosphorylate downstream targets in a signal transduction cascade, eventually leading to cell cycle arrest. A class of checkpoint mediator proteins including BRCA1, MDC1, and 53BP1 has also been identified. These proteins seem to be required for transmitting the checkpoint activation signal to downstream proteins.


title: DNA repair

text: DNA damage checkpoint is a signal transduction pathway that blocks cell cycle progression in G1, G2 and metaphase and slows down the rate of S phase progression when DNA is damaged. It leads to a pause in cell cycle allowing the cell time to repair the damage before continuing to divide.


title: DNA repair

text: Checkpoint Proteins can be separated into four groups: phosphatidylinositol 3-kinase (PI3K)-like protein kinase, proliferating cell nuclear antigen (PCNA)-like group, two serine/threonine(S/T) kinases and their adaptors. Central to all DNA damage induced checkpoints responses is a pair of large protein kinases belonging to the first group of PI3K-like protein kinases-the ATM (Ataxia telangiectasia mutated) and ATR (Ataxia- and Rad-related) kinases, whose sequence and functions have been well conserved in evolution. All DNA damage response requires either ATM or ATR because they have the ability to bind to the chromosomes at the site of DNA damage, together with accessory proteins that are platforms on which DNA damage response components and DNA repair complexes can be assembled.


title: DNA repair

text: An important downstream target of ATM and ATR is p53, as it is required for inducing apoptosis following DNA damage. The cyclin-dependent kinase inhibitor p21 is induced by both p53-dependent and p53-independent mechanisms and can arrest the cell cycle at the G1/S and G2/M checkpoints by deactivating cyclin/cyclin-dependent kinase complexes.


title: DNA repair

text: The SOS response is the changes in gene expression in "Escherichia coli" and other bacteria in response to extensive DNA damage. The prokaryotic SOS system is regulated by two key proteins: LexA and RecA. The LexA homodimer is a transcriptional repressor that binds to operator sequences commonly referred to as SOS boxes. In "Escherichia coli" it is known that LexA regulates transcription of approximately 48 genes including the lexA and recA genes. The SOS response is known to be widespread in the Bacteria domain, but it is mostly absent in some bacterial phyla, like the Spirochetes.


title: DNA repair

text: The most common cellular signals activating the SOS response are regions of single-stranded DNA (ssDNA), arising from stalled replication forks or double-strand breaks, which are processed by DNA helicase to separate the two DNA strands. In the initiation step, RecA protein binds to ssDNA in an ATP hydrolysis driven reaction creating RecA–ssDNA filaments. RecA–ssDNA filaments activate LexA autoprotease activity, which ultimately leads to cleavage of LexA dimer and subsequent LexA degradation. The loss of LexA repressor induces transcription of the SOS genes and allows for further signal induction, inhibition of cell division and an increase in levels of proteins responsible for damage processing.