query: The Wolf of Wall Street starred an actor.

pos: Kyle Chandler Kyle Martin Chandler ( born September 17 , 1965 ) is an American actor , best known for his roles on Early Edition and as Coach Eric Taylor in the drama series Friday Night Lights , for which he won a Primetime Emmy Award in 2011 . He has starred in the films King Kong ( 2005 ) , The Day the Earth Stood Still ( 2008 ) , Super 8 ( 2011 ) , Argo ( 2012 ) , Zero Dark Thirty ( 2012 ) , The Wolf of Wall Street ( 2013 ) , Carol ( 2015 ) , and Manchester by the Sea ( 2016 ) . In 2015 , he began starring on Netflix 's drama series Bloodline , for which he received his fourth and fifth Primetime Emmy Award nominations .

pos: Jonah Hill Jonah Hill Feldstein ( born December 20 , 1983 ) , better known as Jonah Hill , is an American actor , producer , screenwriter and comedian . Hill is known for his comedic roles in films such as Accepted ( 2006 ) , Grandma 's Boy ( 2006 ) , Superbad ( 2007 ) , Knocked Up ( 2007 ) , Forgetting Sarah Marshall ( 2008 ) , Get Him to the Greek ( 2010 ) , 21 Jump Street ( 2012 ) , This Is the End ( 2013 ) , 22 Jump Street ( 2014 ) and War Dogs ( 2016 ) , as well as his performances in Moneyball ( 2011 ) and The Wolf of Wall Street ( 2013 ) , for which he received Academy Award nominations for Best Supporting Actor .   Hill ranked 28th on Forbes magazine 's ranking of world 's highest paid actors from June 2014 to June 2015 , bringing in $ 16million . As a screenwriter , he contributed to the stories of 21 Jump Street , 22 Jump Street and Sausage Party ( 2016 ) , all of which he also starred in .

pos: Matthew McConaughey Matthew David McConaughey ( -LSB- məˈkɒnəheɪ -RSB- born November 4 , 1969 ) is an American actor . He first gained notice for his breakout role in the coming-of-age comedy Dazed and Confused ( 1993 ) . He appeared in such films as the slasher Texas Chainsaw Massacre : The Next Generation ( 1994 ) , the legal thriller A Time to Kill ( 1996 ) , Steven Spielberg 's historical drama Amistad ( 1997 ) , the science fiction drama Contact ( 1997 ) , the comedy EDtv ( 1999 ) , and the war film U-571 ( 2000 ) .   In the 2000s , Matthew McConaughey became best known for starring in romantic comedies , including The Wedding Planner ( 2001 ) , How to Lose a Guy in 10 Days ( 2003 ) , Failure to Launch ( 2006 ) , Fool 's Gold ( 2008 ) , and Ghosts of Girlfriends Past ( 2009 ) . Since 2011 he has preferred dramatic roles , in such films as The Lincoln Lawyer ( 2011 ) , Bernie ( 2011 ) , Killer Joe ( 2011 ) , The Paperboy ( 2012 ) , Mud ( 2012 ) , Magic Mike ( 2012 ) , The Wolf of Wall Street ( 2013 ) , Dallas Buyers Club ( 2013 ) , Interstellar ( 2014 ) , The Sea of Trees , and Free State of Jones ( both 2016 ) .   McConaughey achieved much success in 2013 for portraying a cowboy diagnosed with AIDS in the biographical film Dallas Buyers Club , which earned him the Academy Award , Golden Globe Award , and Screen Actors Guild Award for Best Actor , among other awards and nominations . In 2014 , he also starred as Rust Cohle in the first season of HBO 's crime anthology series True Detective , for which he won a Critics ' Choice Award and was nominated for an Emmy Award and a Golden Globe Award .

pos: The Wolf of Wall Street (2013 film) The Wolf of Wall Street is a 2013 American biographical black comedy crime film directed by Martin Scorsese . The screenplay by Terence Winter is adapted from the memoir of the same name by Jordan Belfort and recounts Belfort 's perspective on his career as a stockbroker in New York City and how his firm Stratton Oakmont engaged in rampant corruption and fraud on Wall Street that ultimately led to his downfall . Leonardo DiCaprio ( who also co-produced the film ) stars as Belfort , with Jonah Hill as his business partner and friend Donnie Azoff , Margot Robbie as his second wife Naomi Lapaglia and Kyle Chandler as Patrick Denham , the FBI agent who tries to bring him down . Matthew McConaughey , Rob Reiner , Jon Favreau , Joanna Lumley and Jean Dujardin are also featured . The film marks the director 's fifth collaboration with DiCaprio , after Gangs of New York ( 2002 ) , The Aviator ( 2004 ) , The Departed ( 2006 ) and Shutter Island ( 2010 ) , as well as his second collaboration with Winter after the television series Boardwalk Empire ( 2010 -- 14 ) .   The Wolf of Wall Street premiered in New York City on December 17 , 2013 and was released theatrically on December 25 , 2013 in the United States , distributed by Paramount Pictures . The film was the first to be released entirely through digital distribution . It was a major commercial success , grossing more than $ 392 million worldwide during its original theatrical run to become Scorsese 's highest-grossing movie and the 17th-highest-grossing film of 2013 . The film was controversial for its morally ambiguous depiction of events , explicit sexual content , profanity , depiction of hard drug use and the use of animals during production . The film also caused controversy due to revelations that it was financed by illegally obtained funds from 1Malaysia Development Berhad ( 1MDB ) .   The film received mostly positive reviews from critics , with praise for Scorsese 's direction , the comedic performance of DiCaprio and the fast-paced and consistent humor . The film was nominated for several awards including five nominations at the 86th Academy Awards ceremony : Best Picture , Best Director for Scorsese , Best Writing ( Adapted Screenplay ) for Winter and Best Actor and Best Supporting Actor nominations for DiCaprio and Hill , respectively . The film did not win in any category , although DiCaprio did win Best Actor -- Motion Picture Musical or Comedy at the 71st Golden Globe Awards , where the film was also nominated for Best Picture -- Musical or Comedy . It was also recognized by numerous other awards ceremonies , as well as guilds and critics ' associations .   The word `` fuck '' and its numerous conjugations are said between 506 and 569 times , making this the film with the most uses of the word in a mainstream , non-documentary film .

pos: Leonardo DiCaprio Leonardo Wilhelm DiCaprio ( -LSB- dᵻˈkæpri.oʊ -RSB- born November 11 , 1974 ) is an American actor , film producer , and environmental activist . DiCaprio began his career by appearing in television commercials in the early 1990s , after which he had recurring roles in various television series such as the soap opera Santa Barbara and the sitcom Growing Pains . He began his film career by starring as Josh in Critters 3 ( 1991 ) . He starred in the film adaptation of the memoir This Boy 's Life ( 1993 ) , and was praised for his supporting role in What 's Eating Gilbert Grape ( 1993 ) . He gained public recognition with leading roles in The Basketball Diaries ( 1995 ) and the romantic drama Romeo + Juliet ( 1996 ) , before achieving international fame with James Cameron 's epic romance Titanic ( 1997 ) , which became the highest-grossing film of all time until Cameron 's science fiction film Avatar ( 2009 ) overtook it .   Since 2000 , DiCaprio has received critical acclaim for his work in a wide range of film genres . DiCaprio 's subsequent films include The Man in the Iron Mask ( 1998 ) , the biographical crime drama Catch Me If You Can ( 2002 ) , and the epic historical drama Gangs of New York ( 2002 ) , which marked his first of many collaborations with director Martin Scorsese . He was acclaimed for his performances in the political war thriller Blood Diamond ( 2006 ) , the neo-noir crime drama The Departed ( 2006 ) , the espionage thriller Body of Lies ( 2008 ) , the drama Revolutionary Road ( 2008 ) , the psychological thriller Shutter Island ( 2010 ) , the science fiction thriller Inception ( 2010 ) , the biographical film J. Edgar ( 2011 ) , the western Django Unchained ( 2012 ) , and the period drama The Great Gatsby ( 2013 ) .   DiCaprio 's portrayals of Howard Hughes in The Aviator ( 2004 ) and Hugh Glass in The Revenant ( 2015 ) won him the Golden Globe Award for Best Actor -- Motion Picture Drama , and his role as Jordan Belfort in The Wolf of Wall Street ( 2013 ) won him the award for Best Actor -- Motion Picture Musical or Comedy . He also won his first Academy Award and BAFTA Award for his performance in The Revenant . DiCaprio is the founder of his own production company , Appian Way Productions .

neg: Alan Wilder (actor) Alan Wilder is an American actor who has appeared on film and television . Alan is also a member of the Steppenwolf Theater Company . He has appeared in over 55 Steppenwolf productions .

neg: Assault on Wall Street Assault on Wall Street ( also known as Attack on Wall Street and formerly known as Bailout : The Age of Greed ) is a 2013 action thriller film written and directed by Uwe Boll , and starring Dominic Purcell . The film stars Purcell as a security guard who struggles to pay for his wife 's medical bills and loses his investments in the 2007 -- 08 financial crisis , prompting a shooting spree on Wall Street after his wife takes her own life .

neg: Fred Aldrich Fred Aldrich ( December 23 , 1904 - January 25 , 1979 ) was an American character actor of both film and television . He would break into the film industry in 1939 , appearing in two films that year in small roles : My Son Is Guilty , and the notable , Confessions of a Nazi Spy , which starred Edward G. Robinson and George Sanders . In the course of his thirty-year career he would appear in over 170 films , in small and bit roles . With the advent of television , Aldrich would work in that medium as well , making his first small screen appearance on I Love Lucy , on which he would appear multiple times over the life of the series .   Over the course of his film career he would appear in such notable films as : Kitty Foyle ( 1940 ) , starring Ginger Rogers and Dennis Morgan ; 1945 's The Picture of Dorian Gray , starring George Sanders ; Tycoon ( 1947 ) , starring John Wayne and Laraine Day ; A Connecticut Yankee in King Arthur 's Court , with Bing Crosby and Rhonda Fleming ; Young Man with a Horn , starring Kirk Douglas , Lauren Bacall , and Doris Day ; the Spencer Tracy and Katharine Hepburn vehicle , Pat and Mike ( 1952 ) ; again with Paul Newman in 1956 's Somebody Up There Likes Me ; The Last Angry Man , starring Paul Muni ; with Rock Hudson and Doris Day in Lover Come Back ( 1961 ) ; the spy spoof , Our Man Flint ( 1966 ) , starring James Coburn ; and 1967 's A Big Hand for the Little Lady , starring Henry Fonda , Joanne Woodward , and Jason Robards .   His television credits include appearances on such shows as The Rifleman , Have Gun - Will Travel , Bat Masterson , The Untouchables , Gunsmoke , Rawhide , and Perry Mason . Aldrich died on January 25 , 1979 .

neg: Will Smith Willard Carroll Smith Jr. ( born September 15 , 1968 ) is an American actor , producer , rapper , and songwriter . In April 2007 , Newsweek called him `` the most powerful actor in Hollywood '' . Smith has been nominated for five Golden Globe Awards and two Academy Awards , and has won four Grammy Awards .   In the late 1980s , Smith achieved modest fame as a rapper under the name The Fresh Prince . In 1990 , his popularity increased dramatically when he starred in the popular NBC television series The Fresh Prince of Bel-Air , which ran for six seasons until 1996 . After the series ended , Smith transitioned from television to film , and has gone on to star in numerous blockbuster films . He is the only actor to have eight consecutive films gross over $ 100 million in the domestic box office , eleven consecutive films gross over $ 150 million internationally , and eight consecutive films in which he starred open at the number one spot in the domestic box office tally .   Smith has been ranked as the most bankable star worldwide by Forbes . As of 2014 , 17 of the 21 films in which he has had leading roles have accumulated worldwide gross earnings of over $ 100 million each , five taking in over $ 500 million each in global box office receipts . As of 2016 , his films have grossed $ 7.5 billion at the global box office . For his performances as boxer Muhammad Ali in Ali ( 2001 ) and stockbroker Chris Gardner in The Pursuit of Happyness ( 2006 ) , Smith received nominations for the Academy Award for Best Actor .

neg: Perry Anzilotti Perry Anzilotti ( born December 11 , 1959 ) is an American television and film actor .

neg: Albert Salmi Albert Salmi ( March 11 , 1928 -- April 22 , 1990 ) was an American actor of stage , film , and television . He was noted as a character actor and appeared in over 150 film and television productions .

neg: Robert H. Harris Robert H. Harris ( born Robert H. Hurwitz , July 15 , 1911 -- November 30 , 1981 ) was an American character actor born in Manhattan .

neg: Gary Cooper filmography The filmography of Gary Cooper chronicles the film appearances of American actor Gary Cooper . After starting his career in 1925 as a film extra and stuntman , Cooper made his official cinematic debut in 1926 in the Samuel Goldwyn production The Winning of Barbara Worth . He went on to become a contract player with Paramount Pictures where he established himself as a popular leading man prior to the end of the silent film era .   Cooper 's future in the sound era was assured with the release of The Virginian ( 1929 ) , his first all-talkie film . For the next 32 years , he would be one of cinema 's top money-making stars . From 1936 to 1957 , Cooper ranked 18 times among the top ten box office attractions -- a record when he died in 1961 , and later surpassed only by John Wayne , who ranked among the top ten 25 times , Clint Eastwood ( 21 times ) and Tom Cruise ( 20 times ) .   Cooper was nominated for the Best Actor Academy Award five times and won twice , for Sergeant York ( 1942 ) and High Noon ( 1952 ) . The latter film boosted his popularity , resulting in him being the number one box office attraction in 1953 . Cooper received a third Academy Award -- an honorary one -- just prior to his death in 1961 . His final film , The Naked Edge , was released shortly after his death .   As of February 2008 , more than half of Gary Cooper 's feature films are available on DVD , while others not yet on home video are available for television broadcast . Unfortunately , at least two of his silent films -- Beau Sabreur ( 1928 ) and The Legion of the Condemned ( 1928 ) -- are now considered lost films . Another of his silent films , Wolf Song ( 1929 ) , was originally released as a part talkie , but survives only as a silent film . One of Cooper 's earliest talkies , Paramount on Parade ( 1930 ) , survives incomplete . The prints that are available for television are missing all but one of the film 's Technicolor scenes -- a partial restoration of these scenes was done by the UCLA Film Archives .   This filmography contains sections for Cooper 's work as an extra in the earliest part of his film career , his feature film appearances , his occasional appearances in short films , and a section for a compilation film . Due to its length ( 92 films ) , the listing of his feature films is divided in four sections . Cooper 's film roles are listed , as well as the names of each film 's director and co-stars . Cooper 's awards and nominations are also listed . Except where noted , all of his films were shot in 35mm black and white . All films released prior to Lilac Time ( 1928 ) are silent films and all from The Virginian ( 1929 ) onward are sound films . The films made during the silent-to-sound transition are noted as being either silent or sound films . As an addendum , Cooper 's handful of television appearances are also listed .

neg: Billy Dee Williams William December `` Billy Dee '' Williams Jr. ( born April 6 , 1937 ) is an American actor , artist , singer , and writer . He is best known for his role as Lando Calrissian in the Star Wars film franchise , as well as acting in the movies Brian 's Song , Nighthawks , The Last Angry Man , Carter 's Army , and for playing Harvey Dent in Tim Burton 's Batman ( 1989 ) .

neg: Bill Raymond William Joseph `` Bill '' Raymond ( born September 9 , 1938 ) is an American actor who has appeared in film , television and theatre since the 1960s .

neg: Seymour Cassel Seymour Joseph Cassel ( born January 22 , 1935 ) is an American actor .   Cassel first came to prominence in the 1960s in the pioneering independent films of writer/director John Cassavetes . The first of these was Too Late Blues ( 1961 ) , followed by Faces ( 1968 ) , for which he was nominated for an Academy Award and won a National Society of Film Critics Award . Cassel went on to appear in Cassavetes ' Minnie and Moskowitz ( 1971 ) , The Killing of a Chinese Bookie ( 1976 ) , Opening Night ( 1977 ) and Love Streams ( 1984 ) .   He has further appeared in a number of independent and Hollywood film productions . Notable titles include Coogan 's Bluff ( 1968 ) , The Last Tycoon ( 1976 ) , Valentino ( 1977 ) , Johnny Be Good ( 1988 ) , Mobsters ( 1991 ) , In the Soup ( 1992 ) , Honeymoon in Vegas ( 1992 ) , Indecent Proposal ( 1993 ) , Beer League ( 2006 ) and Fort McCoy ( 2011 ) . Like Cassavetes , Wes Anderson has frequently cast Cassel , first in Rushmore ( 1998 ) and then in The Royal Tenenbaums ( 2001 ) and The Life Aquatic with Steve Zissou ( 2004 ) .

neg: Wall Street (disambiguation) Wall Street is a street in New York City which runs through the historical center of the Financial District .   Wall Street also refers to :  The Wall Street Journal , a daily newspaper in New York City  Financial District , Manhattan , a New York City neighborhood containing the headquarters of many of the city 's major financial institutions  Financial market of the United States , particularly major participants in New York City  These New York City Subway stations in Manhattan :  Wall Street ( IRT Broadway -- Seventh Avenue Line ) , at Williams Street ; serving the trains  Wall Street ( IRT Lexington Avenue Line ) , at Broadway ; serving the trains  Wall Street ( Winnipeg ) , a street in Winnipeg , Manitoba , Canada  Wall Street ( train ) a former train of the Reading Railroad  Big business , often contrasted with `` Main Street '' small business   In arts and entertainment :  Wall Street ( 1915 photograph )  Wall Street ( 1929 film ) , directed by Roy William Neill  Wall Street ( 1987 film ) , directed by Oliver Stone  Wall Street : Money Never Sleeps , ( 2010 film ) , directed by Oliver Stone , sequel to the 1987 film  Wall Street , a 1997 book by Doug Henwood  `` Wall Street '' , a character in the 2002 film The Transporter

neg: Frank Wolff (actor) Walter Frank Hermann Wolff ( May 11 , 1928 -- December 12 , 1971 ) was an American actor whose film career began with roles in five 1958 -- 61 Roger Corman productions and ended a decade later in Rome , after many appearances in European-made films , most of which were lensed in Italy .

neg: Richard Hart (actor) Richard Comstock Hart ( April 14 , 1915 -- January 2 , 1951 ) was an American actor , who appeared in film and TV productions , but was most active on stage .

neg: William O'Connell (actor) William O'Connell ( born William L. O'Connell Jr. on August 20 , 1933 ) is an American film and television actor .

neg: Oskar Werner Oskar Werner ( 13 November 1922 23 October 1984 ) was an Austrian stage and cinema actor whose prominent roles include two 1965 films , The Spy Who Came in from the Cold and Ship of Fools . Other notable films include Decision Before Dawn ( 1951 ) , Jules and Jim ( 1962 ) , Fahrenheit 451 ( 1966 ) , The Shoes of the Fisherman ( 1968 ) and Voyage of the Damned ( 1976 ) . Werner accepted both stage and film roles throughout his career . He won a Golden Globe for Best Supporting Actor , and had been nominated several times for the Golden Globe , the Academy Award , and the BAFTA Award as well .

neg: Michael Wiseman Michael Wiseman ( born April 12 , 1967 ) is an American television and film actor . He is best known for his portrayal of Johnny Rizzo in the 2012 CBS series Vegas .

neg: Elya Baskin Ilya Zalmanovich Baskin ( Iļja Baskins , Илья́ За́лманович Ба́скин born 11 August 1950 ) , known as Elya Baskin , is an American actor .

neg: Michael T. Weiss Michael Terry Weiss ( born February 2 , 1962 ) is an American actor .

neg: James Wilby James Jonathon Wilby ( born 20 February 1958 ) is an English film , television and theatre actor .


query: Drop Dead Gorgeous features various contestants dying in suspicious ways.

pos: Drop Dead Gorgeous (film) Drop Dead Gorgeous is a 1999 American black comedy film directed by Michael Patrick Jann and starring Kirstie Alley , Ellen Barkin , Kirsten Dunst , Allison Janney , Denise Richards , Brittany Murphy , and Amy Adams in her film debut . Shot in a mockumentary format , it follows the contestants in a beauty pageant called the Sarah Rose Cosmetics Mount Rose American Teen Princess Pageant , held in the small fictional town of Mount Rose , Minnesota , in which various contestants die in suspicious ways .

neg: Dead State Dead State is a turn-based survival horror role-playing video game developed by DoubleBear Productions and Iron Tower Studios set in a zombie apocalypse scenario . Players are tasked with leading a group of survivors living in a shelter in the fictional town of Splendid , Texas . Dead State was released in December 2014 after having been in Early Access since spring of that year . DoubleBear Productions continued to work on the title and in May 2015 released an `` enhanced edition '' which changed the name to Dead State : Reanimated .

neg: Erotic thriller An Erotic thriller is a film genre defined by a thriller with a thematic basis in illicit romance or erotic fantasy . Most erotic thrillers contain scenes of softcore sex and nudity , but the frequency and explicitness of those scenes varies .   Though similar films appeared as early as the 1960s , erotic thrillers emerged as a distinct genre in the late 1980s , bolstered by the popular success of Adrian Lyne 's Fatal Attraction in 1987 and a quickly expanding domestic and international market for softcore adult entertainment on cable television and home video . The genre had a classic period of growth and expansion in the 1990s , but by the early 2000s declined in production and popular appeal .   The potent combination of danger and romance , catering to both male and female audiences simultaneously , was the primary selling point for erotic thriller films during their classic period . The half-naked bodies displayed on posters , newspaper ads , and video box covers were accompanied by log lines that capture the unmistakable duality of the erotic thriller film :   If you think you can handle her , you 're dead wrong . -- Body Chemistry 3 : Point of Seduction  He was hired to watch . Now he 's tempted to touch . -- Night Eyes  Twin sisters cross the line into a deadly erotic fantasy land . -- Mirror Images   In all , over 300 erotic thriller films were produced in the 1990s , which is comparable to the number of thriller films made in the noir decade of the 1940s . The total number of films in the erotic thriller genre from 1985 to 2005 may number as high as over 500 . Like film noir , the genre has evolved and modernized , and new films continue to be made that are influenced by the classic style .

neg: Desperate Housewives Desperate Housewives is an American television comedy-drama and mystery series created by Marc Cherry , and produced by ABC Studios and Cherry Productions . It originally aired for eight seasons on ABC , from October 3 , 2004 to May 13 , 2012 . Executive producer Cherry served as showrunner . Other executive producers since the fourth season included Bob Daily , George W. Perkins , John Pardee , Joey Murphy , David Grossman , and Larry Shaw .   Set on Wisteria Lane , a street in the fictional town of Fairview in the fictional Eagle State , Desperate Housewives follows the lives of a group of women as seen through the eyes of their late friend and neighbor who committed suicide in the pilot episode . The storyline covers 13 years of the women 's lives over eight seasons , set between the years 2004 -- 2008 , and later 2013 -- 2017 ( the story arc includes a five-year passage of time , as well as flashbacks ranging from the 1980s to the 2020s ) . They work through domestic struggles and family life , while facing the secrets , crimes and mysteries hidden behind the doors of their -- on the surface -- beautiful and seemingly perfect suburban neighborhood .   The series features an ensemble cast , headed by Teri Hatcher as Susan Mayer , Felicity Huffman as Lynette Scavo , Marcia Cross as Bree Van de Kamp , and Eva Longoria as Gabrielle Solis . Brenda Strong narrates the series as the late Mary Alice Young , appearing sporadically in flashbacks or dream sequences .   Desperate Housewives was well received by viewers and critics alike . It won multiple Primetime Emmy , Golden Globe and Screen Actors Guild Awards . From the 2004 -- 05 through the 2008 -- 09 television seasons , its first five seasons were rated amongst the top ten most-watched series . In 2007 , it was reported to be the most popular show in its demographic worldwide , with an audience of approximately 120 million and was also reported as the third most watched television series in a study of ratings in twenty countries . In 2012 , it remained the most-watched comedy series internationally based on data from Eurodata TV Worldwide , which measured ratings across five continents ; it has held this position since 2006 . Moreover , it was the third highest revenue earning series for 2010 , with $ 2.74 million per half an hour . The show was ranked at number fifty-six on Entertainment Weekly `` New TV Classics '' list .   In 2011 , it was confirmed that Desperate Housewives would conclude after its eighth season ; the series finale aired on May 13 , 2012 . By the end of the series , it had surpassed Charmed as the longest running hour-long television series featuring all female leads by two episodes .

neg: Dead, Everywhere Dead , Everywhere is the second full-length album by American metalcore band Tear Out the Heart . The album was released on January 27 , 2015 , through Victory Records .   On December 8 , 2014 , pre-orders for the upcoming album were announced , along with the music video for the new album 's first single `` Feel Real '' which premiered on Revolver . The following week Revolver also premiered the first part in a series of track-by-track videos containing clips from the songs and the band 's lead vocalist Tyler Konersman explaining the meaning behind each songs lyrics .

neg: Funny or Die Funny or Die is a comedy video website and film/TV production company founded by Will Ferrell , Adam McKay and Chris Henchy . The website Funny Or Die contains exclusive material from a regular staff of in-house writers , producers , and directors , and occasionally from a number of famous contributors like Judd Apatow , James Franco , and Norm Macdonald . The production company makes TV shows like truTV 's Billy on the Street , Comedy Central 's @midnight , and Zach Galifianakis 's popular Emmy-winning web series Between Two Ferns .   Many videos on the site feature well-known actors ( examples include Steve Carell , Charlie Sheen , Ryan Gosling , Patrick Stewart , Daniel Radcliffe , Sophia Bush , Mila Kunis , AnnaSophia Robb , Hilary Duff , Adam West , James Van Der Beek , Jim Carrey , Ariel Winter , and Selena Gomez ) . Michael Kvamme , an aspiring young comedian , came up with a concept for a new kind of comedy site ; and the site was developed by Randy Adams .   Funny Or Die launched on April 12 , 2007 with the site 's first video , `` The Landlord '' . `` The Landlord '' has received over 84 million views and features Ferrell confronted by a swearing , beer-drinking two-year-old landlord . In June 2007 , they received venture capital funding from Sequoia Capital , and in June 2008 , they announced a partnership with HBO . On August 3 , 2016 , Funny or Die shut-down one of its California offices , reducing its headcount by 30 % to 95 employees , with the announcement coming just two month after the new CEO , Mike Farah , took office

neg: Procedural drama A procedural drama is a genre of television programming which focuses on how crimes are solved or some other aspect of a law enforcement agency , legislative body , or court of law . Some dramas include a lab or conference room with high-tech or state-of-the-art equipment where the main characters meet to work out the problem . Shows usually have an episodic format that does not require the viewer to have seen previous episodes . Episodes typically have a self-contained , also referred to as stand-alone , plot that is introduced and resolved within the same episode .   The procedural format is popular around the world . In 2011 , the director of a TV consultancy said , `` The continuing trend is for procedurals because they use a predictable structure . '' Due to their stand-alone episodic nature , they are more accessible to new viewers than serials . Self-contained episodes also make it easier for viewers to return to a show if they have missed some episodes . In general , procedural dramas can usually be re-run with little concern for episode order .   Procedurals are often criticized for being formulaic . Procedurals are also generally less character-driven than serialized shows . However , some procedurals have more character emphasis than is typical of the format . Some may occasionally feature a storyline stretching over several episodes .   A popular variant is the police procedural .

neg: Deathtrap Deathtrap may refer to :   Deathtrap ( play ) , a 1978 play by Ira Levin which received a Tony Award nomination for Best Play  Deathtrap ( film ) , a 1982 film based on the Levin play  Death Trap , a 1977 film better known as Eaten Alive  Deathtrap ( plot device ) , a plot device in fiction and drama  Deathtrap , a hypothetical organism from Extraterrestrial  `` Death Trap '' ( Star Wars : The Clone Wars ) , a second season episode of Star Wars : The Clone Wars  Deathtrap , a character from Stormwatch , leader of a team of mercenaries  The Death Trap , a 1984 video game developed and published by Square for the NEC PC-8801 , NEC PC-9801 , and Fujitsu FM-7  Will : The Death Trap II , sequel to the previous game  Deathtrap ( video game ) , a 2015 video game developed and published by NeocoreGames  `` Death Trap '' , a song by Hawkwind from their 1979 album PXR5  `` Death Trap '' , a song by Pantera from their 1988 album Power Metal  `` Death Trap '' , a song by Gravediggaz from their 1997 album 6 Feet Deep  Death Trap , kind of a stage fatality which occurs in Mortal Kombat during the fight  A political neologism used to condemn the budget proposal The Path to Prosperity  Deathtrap , a robot constructed by a character called Gaige to serve as her personal bodyguard in the fictional Borderlands series of games programmed by Gearbox  A slang term for a consumer product that does not meet safety regulations and may pose a risk of injury or death

neg: Death Faces Death Faces , also released as Death Faces IV , also ` Dying : Last seconds of Life ' , and ( in a re edited version ) ` Beyond Reality ' , is a mockumentary about cannibalism released directly to video originally in 1988 .   Narrated by `` Prof. Bizarro Blackstone '' , the film is actually footage from various horror films about cannibalism , and newsreel footage of Bonnie and Clyde , John Dillinger , Adolf Hitler . One sequence involves the Kikuyu tribes people of Kenya , ( the film incorrectly says that they are from Papua New Guinea ) as well as various stock car crashes , and the John F. Kennedy assassination .   The direction is credited to `` Countess Victoria Bloodhart '' and Steve White , the writing to `` S. Sebastian Shock '' , the direction and production to `` Damian B. Gravenhorse PhD . '' , with one segment credited to producer `` Mink De Ronda '' . It was re edited and re released as Beyond Reality , which is credited to Steve White . There are no other technical credits given to the film .   With the exception of a few brief scenes , the entire video is in black and white . Footage from this video was later edited into Banned from Facez , parts 3 and 4 .   A sequel was also released straight to video : ` Dying : Last Seconds of Life , Part II ' , also in 1988 .

neg: Dead Letters (Millennium) '' ` Dead Letters '' is the third episode of the first season of the American crime-thriller television series Millennium . It premiered on the Fox network on November 8 , 1996 . The episode was written by Glen Morgan and James Wong , and directed by Thomas J. Wright . `` Dead Letters '' featured guest appearances by Chris Ellis , Ron Halder and James Morrison .   Millennium Group consultant Frank Black ( Lance Henriksen ) is sent to evaluate a prospective member of the group , who perform private investigative work and liaise with law enforcement . Meeting this hopeful member , Jim Horn ( Morrison ) , Black is drawn to investigate a serial killer operating in the area ; while Horn begins to unravel under the strain of the case .   Several of the cast and crew made their first contributions to the series in `` Dead Letters '' , with Wright , Morgan , Wong and Ellis all returning for future episodes . Production of `` Dead Letters '' impressed other series regulars -- series writer Chip Johannessen praised the script 's attention to detail , while producer John Peter Kousaskis called positive attention to its physical and make-up effects .

neg: Bop Gun (Homicide: Life on the Street) `` Bop Gun '' is the second season premiere of the American police drama television series Homicide : Life on the Street , and the tenth overall episode of the series . It originally aired on NBC in the United States on January 6 , 1994 . In the episode , the Baltimore homicide unit investigates the shooting death of the wife of a tourist , played by guest star Robin Williams .   The episode was written by David Mills and David Simon based on a story by executive producer Tom Fontana , and directed by Stephen Gyllenhaal . In response to network feedback and poor ratings from the first season , `` Bop Gun '' marked several changes in the series , including a less bleak visual style and a greater focus on one plot , rather than multiple subplots . It was also the first episode to focus primarily on a homicide victim , rather than on the detectives . Simon felt the dialogue was realistic , especially that of the dark humor employed by detectives as a coping mechanism for dealing with the horrors of the job .   Williams previously worked with Homicide executive producer Barry Levinson on the films Good Morning , Vietnam ( 1987 ) and Toys ( 1992 ) . This led to speculation that Williams took the role on `` Bop Gun '' as a favor to Levinson , but the actor insisted it was out of admiration for the series itself . A young Jake Gyllenhaal , the son of the episode 's director , makes an appearance as Williams ' son . The episode was the first to feature Chris Tergesen as music coordinator , which resulted in the use of more songs than previous episodes , including `` Killer '' by Seal and `` Feels Like Rain '' by Buddy Guy .   `` Bop Gun '' was seen by 16.3 million viewers , one of the highest Nielsen ratings of the week , thanks in large part due to interest in Williams ' appearance . The episode received generally positive reviews , with several particularly complimenting the dramatic performance by Williams . `` Bop Gun '' won a Writers Guild of America Award for Best Screenplay of an Episodic Drama . Williams also received an Emmy Award nomination for Guest Actor in a Drama Series . The episode , along with the rest of the first and second seasons of Homicide : Life on the Street was released on DVD in the United States on May 27 , 2003 .

neg: Negligent homicide Negligent homicide is a criminal charge brought against a person who , through criminal negligence , allows another person to die .   Negligent homicide is a lesser included offense to first and second degree murder , in the sense that someone guilty of this offense can expect a more lenient sentence , often with imprisonment time comparable to manslaughter . U.S. states all define negligent homicide by statute . In some states , the offense includes the killing of a person while driving under the influence of drugs or alcohol .   Examples include the crash of Aeroperu Flight 603 near Lima , Peru . The accident was caused by a piece of duct tape that was accidentally left over the static ports ( on the bottom side of the fuselage ) after cleaning the aircraft , which led to the crash . Employee Eleuterio Chacaliaza left the tape on by accident and was charged with negligent homicide . Other times , an intentional killing may be negotiated down to the lesser charge as a compromised resolution of a murder case , as in the case of former UFC fighter Gerald Strebendt 's intentional shooting of an unarmed man after a traffic altercation .

neg: Death row Death row is a special section of a prison in the United States that houses inmates who are awaiting execution after being sentenced to death for the conviction of a capital crime . The US is the only Western country that still applies the death penalty for capital crimes . Thirty-one of its 50 states and the federal government authorize this penalty . But by 2016 , sixteen of these states and the federal government had a formal or `` de facto '' moratorium , due in large part to questions about the death penalty itself or the use of lethal injection as a method of execution .   `` Death row '' is a term also used figuratively to describe the state of awaiting execution ( `` being on death row '' ) , even in places where no special facility or separate unit for condemned inmates exists . After a person is found guilty of a capital offense , the judge will give the jury the option of imposing a death sentence or life imprisonment without the possibility of parole ( LWOP ) . It is up to a jury to decide whether to give the death sentence ; this usually has to be a unanimous decision . If sentenced to death , a convict will remain on death row during appeal and habeas corpus procedures , which can take years . Since 1973 and later , with an increasing number of persons being freed since 1993 , some 157 persons as of January 2017 have been exonerated on appeal and released from death row . Wrongful convictions have been proven based on DNA evidence , informants retracting testimony or being proven false , prosecutorial misconduct , racial bias in jury selection , and other constitutional issues .

neg: Faked death A faked death , also called a pseudocide , is a case in which an individual leaves evidence to suggest that they are dead to mislead others . This is done for a variety of reasons , such as to fraudulently collect insurance money or to avoid capture by law enforcement for some other crime .   People who fake their own deaths sometimes do so by pretend drownings , because it provides a plausible reason for the absence of a body .   There are several how-to books on the subject of faking one 's death , including How to Disappear Completely and Never Be Found .

neg: Grave Danger `` Grave Danger '' is the fifth season finale of the American crime drama CSI : Crime Scene Investigation , which is set in Las Vegas , Nevada . This two-parter was directed by Quentin Tarantino and was aired on May 19 , 2005 . The episode features veteran actors Tony Curtis and Frank Gorshin as long-time friends of character Sam Braun . Gorshin died two days before the episode aired in the United States . The episode was later dedicated to his memory .

neg: Dead Serious (EP) Dead Serious is the third release , and second EP by Hullabaloo . It was recorded in 1990 by Paul Kolderie at the Fort Apache Studios in Cambridge , Massachusetts . It was released by Toxic Shock in the United States and Musical Tragedies in Europe . The band 's lineup had changed significantly since their previous release , Beat Until Stiff . Their previous bass player ( Pete Foley ) had left the band . He was replaced on bass by former drummer John Quinn , who was in turn replaced on drums by Chris Rossow . In addition , the band added a second guitar player , Kevin James , formerly of noise-rock instrumental band The Loving Six . James also produced the recording .   The five original songs on the EP show that the transition started with Beat Until Stiff had completed , as band 's sound had moved away from punk , more fully into the territory of grunge . The extra guitar makes for a much heavier sound , and the tempos are slower and songs longer that on previous releases . Nonetheless , the band continued to experiment with unusual song forms and odd meters . And the unusual instrumentation comes to the forefront : the song `` Die Laughing '' begins with a prominent , blaring trumpet solo , and `` Curse of Civilization '' features TQ on an extended sax solo as well .   The record also includes a cover of Led Zeppelin 's `` The Rain Song '' in which the organ parts are transcribed and played by TQ on saxophones .   This record caused quite a stir in Europe due to its cover art . The cover was censored , but the Musical Tragedies label allowed consumers to obtain a sticker with the missing organs if they sent in pornography .   The CD , released in 1991 , includes all of Beat Until Stiff as well , plus Hullabaloo 's cover of Deep Purple 's `` Highway Star '' , previously released on the 7 '' compilation single `` Noise from Nowhere Vol . 2 '' on Toxic Shock .   As with Beat Until Stiff before it , Dead Serious was recorded at the Fort Apache Studios by Paul Q. Kolderie .

neg: Criminal Minds: Suspect Behavior Criminal Minds : Suspect Behavior is an American police procedural drama starring Forest Whitaker and Janeane Garofalo that aired on CBS . The show debuted on February 16 , 2011 , as a spin-off of another series Criminal Minds aired on the same network , and is the second show in the Criminal Minds franchise . This edition 's profiling team also worked for the Federal Bureau of Investigation 's Behavioral Analysis Unit ( BAU ) in Quantico , Virginia . In an April 2010 episode of Criminal Minds ( `` The Fight '' ) , during the show 's fifth season , the original team met the new team and worked with them to find a San Francisco serial killer , with the episode serving as the new series ' backdoor pilot .   Just like the parent series , CBS owned the underlying North American rights , while ABC owned the international rights . The series premiered on February 16 , 2011 , and filled the Wednesday 10:00 pm time slot , airing after Criminal Minds .   Due to low ratings , CBS canceled the series on May 17 , 2011 , and aired its final episode eight days later . On September 6 , 2011 , CBS released the complete series as a four-disc set , packaged as `` The DVD Edition . '' There are numerous special features and two episode commentaries with the cast and crew . The set includes the backdoor pilot from season five of the original show . The series is also carried in rerun form on Ion Television as part of their existing agreement to carry Criminal Minds .

neg: The End of Heartache The End of Heartache is the third studio album by American metalcore band Killswitch Engage . It was released on May 11 , 2004 through Roadrunner Records . It is the first album to feature lead vocalist Howard Jones . It is also the first album with Justin Foley also from Blood Has Been Shed joined the bands as the drummer also making his first recording on this album .   The new lineup played on the 2003 Ozzfest and the MTV2 Headbangers Ball tour . The first recording was the song `` When Darkness Falls '' appearing on the soundtrack to the 2003 horror film Freddy vs. Jason . The End of Heartache was released on May 11 , 2004 . The album debuted in the top 40 of the Australian album charts on May 17 , 2004 following a successful tour of that country with Anthrax .   The title track was nominated for Best Metal Performance for the 47th Annual Grammy Awards .   Two music videos for `` Rose of Sharyn '' and `` The End of Heartache '' were filmed in promotion of the album . `` Rose of Sharyn '' had the group performing in a sunny desert with blood dripping from dead branches to form words . `` The End of Heartache '' featured a darkly lit performance with various computer animated imagery with scenes from Resident Evil : Apocalypse dotted throughout . Both videos saw notable airplay on Headbanger 's Ball .   In 2005 , a special edition of the album was released which contained 6 additional tracks .   The album was certified Gold by the RIAA on December 7 , 2007 .

neg: Homicide in Spain Homicide , according to the Spanish Criminal Code 1995 is a crime which contravenes the legal right to `` independent human life '' . It is found in article 138 which states : `` He who kills another will be punished , as a defendant of homicide , with a prison sentence of ten to fifteen years '' .   The main legal concept in article 138 is bad faith . It may be present in any form , whether direct or indirect . The active subject ( he who kills ) as well as the passive subject ( he who is killed ) are universal , meaning that either can be any person , regardless of the circumstances .   Homicide committed by grave recklessness is covered in article 142 , which includes both reckless homicide by weapons or motor vehicles and homicide caused by professional recklessness . It states :   `` 1 . He who by grave recklessness causes the death of another will be punished , as a defendant of reckless homicide , with a prison sentence of one to four years .   2 . When the reckless homicide is committed using a motor vehicle , a motorcycle or a firearm , the defendant will also be deprived of his right to drive motor vehicles or motorcycles or the right to possess and carry arms for one to six years .   3 . When the homicide is committed by professional recklessness , the defendant will also be prohibited from exercising his profession or office for a period of three to six years . ''   Homicide by minor recklessness is covered in article 621.2 of the Criminal Code :  `` 2 . Those who by minor recklessness cause the death of another person will be punished with a fine of one to two months '' .   It is necessary to indicate that in Spanish law , involuntary homicide is not regulated ; in the majority of cases the law that will be applied will be somewhere between homicide and the criminal concept which is involved .   Other specific concepts , such as parricide and uxoricide also do not exist , since in Spanish criminal law the punishment is founded in the violation of the legal right and not the fact of killing one particular person or another . For these cases , the circumstances of kinship , found in article 23 , could be used as aggravating .


query: Dopamine is in an organ.

pos: Dopamine Dopamine ( DA , contracted from 3,4-dihydroxyphenethylamine ) is an organic chemical of the catecholamine and phenethylamine families that plays several important roles in the brain and body . It is an amine synthesized by removing a carboxyl group from a molecule of its precursor chemical L-DOPA , which is synthesized in the brain and kidneys . Dopamine is also synthesized in plants and most animals .   In the brain , dopamine functions as a neurotransmitter -- a chemical released by neurons ( nerve cells ) to send signals to other nerve cells . The brain includes several distinct dopamine pathways , one of which plays a major role in reward-motivated behavior . Most types of rewards increase the level of dopamine in the brain , and many addictive drugs increase dopamine neuronal activity . Other brain dopamine pathways are involved in motor control and in controlling the release of various hormones . These pathways and cell groups form a dopamine system which is neuromodulatory .   Outside the central nervous system , dopamine functions primarily as a local chemical messenger . In blood vessels , it inhibits norepinephrine release and acts as a vasodilator ( at normal concentrations ) ; in the kidneys , it increases sodium excretion and urine output ; in the pancreas , it reduces insulin production ; in the digestive system , it reduces gastrointestinal motility and protects intestinal mucosa ; and in the immune system , it reduces the activity of lymphocytes . With the exception of the blood vessels , dopamine in each of these peripheral systems is synthesized locally and exerts its effects near the cells that release it .   Several important diseases of the nervous system are associated with dysfunctions of the dopamine system , and some of the key medications used to treat them work by altering the effects of dopamine . Parkinson 's disease , a degenerative condition causing tremor and motor impairment , is caused by a loss of dopamine-secreting neurons in an area of the midbrain called the substantia nigra . Its metabolic precursor L-DOPA can be manufactured , and in its pure form marketed as Levodopa is the most widely used treatment for the condition . There is evidence that schizophrenia involves altered levels of dopamine activity , and most antipsychotic drugs used to treat this are dopamine antagonists which reduce dopamine activity . Similar dopamine antagonist drugs are also some of the most effective anti-nausea agents . Restless legs syndrome and attention deficit hyperactivity disorder ( ADHD ) are associated with decreased dopamine activity . Dopaminergic stimulants can be addictive in high doses , but some are used at lower doses to treat ADHD . Dopamine itself is available as a manufactured medication for intravenous injection : although it can not reach the brain from the bloodstream , its peripheral effects make it useful in the treatment of heart failure or shock , especially in newborn babies .

pos: Brain The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals . The brain is located in the head , usually close to the sensory organs for senses such as vision . The brain is the most complex organ in a vertebrate 's body . In a human , the cerebral cortex contains approximately 15 -- 33 billion neurons , each connected by synapses to several thousand other neurons . These neurons communicate with one another by means of long protoplasmic fibers called axons , which carry trains of signal pulses called action potentials to distant parts of the brain or body targeting specific recipient cells .   Physiologically , the function of the brain is to exert centralized control over the other organs of the body . The brain acts on the rest of the body both by generating patterns of muscle activity and by driving the secretion of chemicals called hormones . This centralized control allows rapid and coordinated responses to changes in the environment . Some basic types of responsiveness such as reflexes can be mediated by the spinal cord or peripheral ganglia , but sophisticated purposeful control of behavior based on complex sensory input requires the information integrating capabilities of a centralized brain .   The operations of individual brain cells are now understood in considerable detail but the way they cooperate in ensembles of millions is yet to be solved . Recent models in modern neuroscience treat the brain as a biological computer , very different in mechanism from an electronic computer , but similar in the sense that it acquires information from the surrounding world , stores it , and processes it in a variety of ways .   This article compares the properties of brains across the entire range of animal species , with the greatest attention to vertebrates . It deals with the human brain insofar as it shares the properties of other brains . The ways in which the human brain differs from other brains are covered in the human brain article . Several topics that might be covered here are instead covered there because much more can be said about them in a human context . The most important is brain disease and the effects of brain damage , that are covered in the human brain article .

neg: Brodmann area 12 Brodmann area 12 is a subdivision of the cerebral cortex of the guenon defined on the basis of cytoarchitecture . It occupies the most rostral portion of the frontal lobe . Brodmann-1909 did not regard it as homologous , either topographically or cytoarchitecturally , to rostral area 12 of the human . Distinctive features ( Brodmann-1905 ) : a quite distinct internal granular layer ( IV ) separates slender pyramidal cells of the external pyramidal layer ( III ) and the internal pyramidal layer ( V ) ; the multiform layer ( VI ) is expanded , contains widely dispersed spindle cells and merges gradually with the underlying cortical white matter ; all cells , including the pyramidal cells of the external and internal pyramidal layers are inordinately small ; the internal pyramidal layer ( V ) also contains spindle cells in groups of two to five located close to its border with the internal granular layer ( IV ) .   It is indirectly connected to the global palladius as well as the substantia nigra , due to efferents to the striatum . Glutaminergic input is turned into GABAergic input there , which allows the frontal lobes to exhibit some control over basal ganglia activity .

neg: Glutamate receptor Glutamate receptors are synaptic receptors located primarily on the membranes of neuronal cells . Glutamate ( the conjugate base of glutamic acid ) is abundant in the human body , but particularly in the nervous system and especially prominent in the human brain where it is the body 's most prominent neurotransmitter , the brain 's main excitatory neurotransmitter , and also the precursor for GABA , the brain 's main inhibitory neurotransmitter . Glutamate receptors are responsible for the glutamate-mediated postsynaptic excitation of neural cells , and are important for neural communication , memory formation , learning , and regulation .   Glutamate receptors are implicated in a number of neurological conditions . Their central role in excitotoxicity and prevalence in the central nervous system has been linked or speculated to be linked to many neurodegenerative diseases , and several other conditions have been further linked to glutamate receptor gene mutations or receptor autoantigen/antibody activity .

neg: RTI-112 RTI ( -4229 ) -112 ( 2β-carbomethoxy-3β - ( 3-methyl-4-chlorophenyl ) tropane ) is a synthetic stimulant drug from the phenyltropane family . In contrast to RTI-113 , which is DAT selective , RTI-112 is a nonselective triple reuptake inhibitor .   In vitro tests show a very similar serotonin transporter ( SERT ) / dopamine transporter ( DAT ) / norepinephrine transporter ( NET ) selectivity to cocaine , although in vivo behaviour is different :   `` The nonselective monoamine transporter inhibitor RTI-126 and the DAT-selective inhibitors RTI-150 and RTI-336 both had a faster rate of onset ( 30 min ) and a short duration of action ( 4h ) . In contrast , the nonselective monoamine transporter inhibitor RTI-112 had a slower rate of onset ( 30 -- 60 min ) and a longer duration of action ( 10h ) . The DAT-selective inhibitors RTI-171 and RTI-177 also had slower rates of onset ( 30 -- 120 min ) , but RTI-171 had a short duration of action ( 2.5 h ) while RTI-177 had a very long duration of action ( 20 h ) . ''   The efficacy of cocaine analogs to elicit self-administration is related to the rate at which they are administered . Slower onset analogs are less likely to function as behavioral stimulants than analogs eliciting a faster rate of onset . Nonselective analogs are less likely to function as `` reinforcers '' than reuptake inhibitors that have DAT specificity .   In order for a dopamine reuptake inhibitor ( DRI ) such as cocaine to induce euphoria , PET scans on primates reveal that the DAT occupancy needs to be > 60 % .   RTI-112 has equipotent in vitro affinity at the SERT , NET and DAT , respectively . RTI-112 was not reliably self-administered , in contrast to the DAT selective reuptake inhibitors that were used in this study . In vivo at the ED50 , RTI-112 had no DAT occupancy at all . At the ED50 , almost all of the RTI-112 occupied the SERT at this dose . A significantly higher dose was required to get > 70 % DAT occupancy in the case of RTI-112 ; however , RTI-112 was still able to suppress cocaine administration at the ED50 , suggesting a serotonergic mechanism was responsible for this .

neg: Synactive Theory of Newborn Behavioral Organization and Development The Synactive Theory of Newborn Behavioral Organization and Development ( Synaction n. , or Synactive adj. -LSB- from the Greek syn `` together '' and the Latin actio `` action , '' resulting in : `` together in action '' -RSB- ) suggests that development of the human fetus , and later newborn , proceeds through the constant balancing of approach and avoidance behaviors , leading to : 1 ) a continuous interaction of the subsystems ( i.e. , Autonomic , Motor , State and Attention/Interaction , and Regulatory ) and their increasingly defined delineations within the organism , that is the infant , and 2 ) the organism 's interaction with the environment at large . This process is aimed at bringing about the increasingly well-defined species-unique developmental agenda .   Figure 1 ( below ) , provides a graphic representation of the Synactive Theory of development , as applied to both fetal and newborn stages . It focuses upon the infant 's within-organism , four subsystems of functioning , and their continuous interaction with each other and with the environment across time ( i.e. , `` together in action , '' or synaction ) . The four subsystems include the :   Autonomic Subsystem : Expressed in the pattern of respiration ( e.g. , fast , slow , pauses ) color changes ( e.g. , pink , pale , red ) , neurological indicators ( e.g. , seizures , tremulousness ) , and visceral or gut signals such as bowel movements , gagging , and hiccoughing ;   Motor Subsystem : Observable through the tone , posture and movement patterns of the infant ;   State and Attention/Interaction Subsystem : Expressed via : 1 ) the range of states available to the infant ( i.e. , deep sleep , light sleep , drowsy , alert , hyperalert , and cry ) , 2 ) how clearly it is to observably differentiate one state from the other , and 3 ) the patterns of transitions from one state to another ( e.g. , smooth well-differentiated state transitions versus abrupt unorganized state transitions ) .   The attention/interaction system is set within this state continuum ( i.e. , from deep sleep to cry ) and represented by the infant 's ability to adjust the robustness and increasing refinement of an alert , attentive state . The infant uses this state to take in cognitive and social information from the environment as well as to bring forth and modify inputs from the surrounding world ; and   Regulatory Subsystem : Behaviorally represented via the observable strategies the infant uses ( Self-Regulation ) in maintaining a balanced , relatively stable and relaxed state of subsystem of functioning or in returning to this a state of subsystem functioning if imbalance , or stress has occurred within the subsystems .   An additional component of the regulatory subsystem is observable in the kind and amount of support offered by the caregiver ( e.g. , supporting a soft , tucked , flexed position of the infant 's arms and legs ) or by the environment ( e.g. , dimming the lights in the nursery ) . This Co-Regulation may be necessary to help the infant 's return to balance in situations when his/her own self-regulatory capacities are exceeded .   Reproduced with permission from Als , H. Toward a synactive theory of development : Promise for the assessment of infant individuality . Infant Mental Health Journal . 1982 : ( 3 ) : 229-243 ; p. 234 .   The graphic representation of the Synactive Theory above depicts the developing organism , that is , the infant , in constant interaction with the environment from within the womb to the newborn intensive care unit ( NICU ) , and the caregiving family 's support in the NICU , to the family in their home . Newborn infants are actively striving for their next steps in development , while depending upon `` good enough '' environments and care to assure progress along their developmental agenda .   The Synactive Theory of Development continues to be instrumental in guiding clinicians ( e.g. , neonatologist , nurses , psychologists , developmental specialists , physical/occupational therapists , etc. ) and researchers in their understanding of the often very small steps in development that prematurely born and other high risk newborns attempt to accomplish ( which are major steps for their immature or injured brain ) . This theory gives professionals the framework and tools with which to identify the infant 's strengths , challenges and accomplishments . Such accomplishments may include breathing , sucking and swallowing in a coordinated sequence ; moving food down into and through the stomach and intestinal track instead of upwards , leading to reflux and vomiting ; looking at the caregiver and breathing at the same time , as well as many others .   The Synactive Theory is the foundation of both : 1 ) the Assessment of Preterm Infants ' Behavior ( APIB ) , a standardized comprehensive newborn test , and 2 ) the Newborn Individualized Developmental Care and Assessment Program ( NIDCAP ) , which is the care and intervention approach , that focuses on each infant 's behavioral cues ( e.g. , hand ( s ) to mouth , bracing with feet against a supporting surface ) in order to support the infant 's strengths and reduce the infant 's vulnerabilities . The infant 's family is viewed as the infant 's most important nurturer and is integrated in all care from the infant 's birth on throughout the infant 's hospitalization .

neg: Adrenergic receptor autoantibodies Adrenergic receptor autoantibodies   The adrenergic receptors ( or adrenoreceptors ) are a class of cell membrane-bound protein receptors throughout the body that are targets of the catecholamines , especially norepinephrine ( or noradrenaline ) and epinephrine ( or adrenaline ) . The binding to these receptors by catecholamines will generally stimulate the sympathetic nervous system , the arm of the autonomic nervous system responsible for the fight-or-flight response .   The implications of high titers of these circulating antibodies are still being worked out and further investigated . There is compelling evidence that autoimmunity against this class of G protein-coupled receptors results in a variety of pathologies .   Associated pathologies :   Cardiovascular diseases and events :   Circulating autoantibodies to adrenergic receptors have been identified in numerous heart diseases and cardiac symptoms . Laboratory models have revealed a mechanism by which adrenergic autoantibodies accomplish their effects on the cardiovascular system . `` Beta1 autoantibodies trigger conformational changes in the receptor , attenuate receptor internalization . The combination of these two properties can result in bimodal effects on receptor activity that are meaningful for basal activity and chronotropic catecholamine responses of human cardiomyocytes . ''   Beta-1 adrenergic receptors are the primary receptor of the heart and , therefore , autoantibodies to these receptors have been tied to many different heart diseases .   Autoantibodies to beta1-adrenergic receptors are linked to chronic heart failure . However , it has been proposed that both beta1-adrenergic receptor polymorphisms and autoantibodies could be working together in the development of chronic heart failure . Cardiomyopathy due to autoimmune dysregulation and production of autoantibodies has been seen in humans and reproduced in animal models . In rabbit models , increased expression of autoantibodies has been directly correlated with induction of atrial fibrillation . In canine models inoculated with adrenergic autoantibodies , it has been shown that beta blockers can negate certain cardiac arrhythmias . Refractory Hypertension associated with autoantibodies to beta1-adrenergic receptors has been documented in diabetic patients .   While the exact pathophysiology of Chagas disease is not completely understood , some models have shown that an overstimulation of the immune system causes production of adrenergic autoantibodies . Current research is trying to determine the exact role of these autoantibodies and whether they correlate with the symptomatology of Chagas disease .   Postural Orthostatic Tachycardia Syndrome   The Heart Rhythm Institute at the University of Oklahoma points to an autoimmune basis in a condition that presents as chronic malfunction of the autonomic nervous system . The work of endocrinology labs have correlated autoantibodies to the beta-adrenergic receptors with Postural Orthostatic Tachycardia Syndrome ( POTS ) .   Doctors compare the level of disability seen in POTS to the quality of life experienced in conditions like Chronic Obstructive Pulmonary Disease ( COPD ) or congestive heart failure . With the vast and vague symptomatology , and no previously known etiology , diagnosis and treatment proved elusive and challenging . The identification of these antibodies and the development of better testing provide hope for more targeted therapies and better treatment outcomes .   Chronic Fatigue Syndrome :   Chronic Fatigue Syndrome ( CFS ) , a disease characterized by profound fatigue , sleep abnormalities , pain , and other symptoms that are made worse by exertion , is infamous for its confounding etiology . Studies have revealed the specific connection between infection-trigger and disease onset in a cohort of Chronic Fatigue Syndrome patients . These patients showed significantly elevated antibodies to beta2-adrenergic receptors . Future research solidifying this correlation of CFS with autoantibodies to adrenergic receptors would be useful to clinicians tackling this difficult-to-treat condition that affects 200,000 people per year in the US .   Other :   Experimental studies observed that activating autoantibodies to the beta1/2-adrenergic and M2 muscarinic receptors are associated with atrial tachyarrhythmias in patients with hyperthyroidism . Additional research into the prevalence of these biomarkers in Grave 's Disease ( Grave 's Hyperthyroidism ) showed facilitated triggering of pulmonary veins and atrial fibrillation .   Adrenergic autoantibodies have been linked to Buerger 's disease ( thromboangiitis obliterans ) . Buerger 's disease is a rare disease in which the arteries and veins in the arms and legs become inflamed , swell and can become blocked with blood clots , also known as thrombi .

neg: Dolasetron Dolasetron ( trade name Anzemet ) is a serotonin 5-HT3 receptor antagonist used to treat nausea and vomiting following chemotherapy . Its main effect is to reduce the activity of the vagus nerve , which is a nerve that activates the vomiting center in the medulla oblongata . It does not have much antiemetic effect when symptoms are due to motion sickness . This drug does not have any effect on dopamine receptors or muscarinic receptors .   Dolasetron breaks down slowly , staying in the body for a long time . One dose usually lasts 4 to 9 hours and is usually administered once or twice daily . This drug is removed from the body by the liver and kidneys .

neg: Catechol-O-methyl transferase Catechol-O-methyltransferase ( COMT ; ) is one of several enzymes that degrade catecholamines ( such as dopamine , epinephrine , and norepinephrine ) , catecholestrogens , and various drugs and substances having a catechol structure . In humans , catechol-O-methyltransferase protein is encoded by the COMT gene . Two isoforms of COMT are produced : the soluble short form ( S-COMT ) and the membrane bound long form ( MB-COMT ) . As the regulation of catecholamines is impaired in a number of medical conditions , several pharmaceutical drugs target COMT to alter its activity and therefore the availability of catecholamines . COMT was first discovered by the biochemist Julius Axelrod in 1957 .

neg: Alpha-Methylserotonin α-Methylserotonin ( αMS ) , also known as α-methyl-5-hydroxytryptamine ( α-methyl-5-HT ) or 5-hydroxy-α-methyltryptamine ( 5-HO-αMT ) , is a tryptamine derivative closely related to the neurotransmitter serotonin ( 5-HT ) . It acts as a non-selective serotonin receptor agonist and has been used extensively in scientific research to study the function of the serotonin system .   Unlike serotonin , αMS is not metabolized by monoamine oxidase on account of the α-methyl substituent blocking the enzyme 's access to the amine . As a result , it has a much longer half-life in comparison . Similarly to serotonin however , αMS poorly crosses the blood-brain-barrier due to its free hydroxyl group , and thus has only weak or no central effects when administered peripherally .   α-Methyltryptophan ( αMTP ) is a prodrug to αMS which does cross the blood-brain-barrier and thus efficiently delivers αMS into the central nervous system . As a result , αMTP acts as an orally bioavailable false or substitute neurotransmitter for serotonin , and has been suggested as a possible therapeutic agent in the treatment of disorders where serotonin is deficient . The O-methylated analogue of αMS , 5-MeO-αMT , also readily enters the brain and could be used for this purpose as well .

neg: Dopamine releasing agent A dopamine releasing agent ( DRA ) is a type of drug which induces the release of dopamine in the body and/or brain .   No selective DRAs are currently known . Many releasing agents of both dopamine and norepinephrine ( norepinephrine-dopamine releasing agents , or NDRAs ) and of serotonin , norepinephrine , and dopamine are known ( serotonin-norepinephrine-dopamine releasing agents , or SNDRAs ) , however . Examples of NDRAs include amphetamine and methamphetamine , and an example of an SNDRA is MDMA . These drugs are frequently encountered as drugs of abuse .   A closely related type of drug is a dopamine reuptake inhibitor ( DRI ) . Various selective DRIs are known , in contrast to the case of DRAs . It is particularly of note that the mechanism of action at DAT for dopamine releasers/substrates is entropy-driven ( i.e. hydrophobic ) , whereas for dopamine re-uptake inhibitors it is enthalpy-driven ( i.e. conformational change ) .   There is some , albeit mixed , in vitro evidence that the antidepressant and modestly selective DRI amineptine may in addition to inhibiting the reuptake of dopamine selectively induce the presynaptic release of dopamine without affecting that of norepinephrine or serotonin .

neg: Neurophysiology Neurophysiology ( from Greek νεῦρον , neuron , `` nerve '' ; φύσις , physis , `` nature , origin '' ; and - λογία , - logia , `` knowledge '' ) is a branch of physiology and neuroscience that is concerned with the study of the functioning of the nervous system . The primary tools of basic neurophysiological research include electrophysiological recordings , such as patch clamp , voltage clamp , extracellular single-unit recording and recording of local field potentials , as well as some of the methods of calcium imaging , optogenetics , and molecular biology .   Neurophysiology is related to electrophysiology , neurobiology , psychology , neurology , clinical neurophysiology , neuroanatomy , cognitive science , biophysics , mathematical biology , and other sciences concerning the brain .

neg: Human brain The human brain is the central organ of the human nervous system . The human brain , with the spinal cord , makes up the central nervous system . The brain consists of the cerebrum , the brainstem and the cerebellum . The brain is the organ that controls most of the activities of the body . The brain processes , integrates , and coordinates all of the information it receives from the sense organs . Sensory information is interpreted and analysed , and decisions are made as to the instructions transmitted to the rest of the body . The brain is contained in , and protected by , the skull bones of the head .   The cerebrum is the largest part of the human brain . It is divided into two cerebral hemispheres which are covered by the cerebral cortex . The cortex is an outer layer of grey matter , that covers the core of white matter . The cortex is split into the neocortex and the much smaller allocortex . The neocortex is made up of six neuronal layers , and the allocortex has three or four such layers . Each hemisphere is conventionally divided into four lobes -- the frontal , temporal , parietal , and occipital lobes . The frontal lobe is associated with executive functions including self-control , planning , reasoning , and abstract thought , while the occipital lobe is dedicated to vision . Within each lobe , there are also cortical areas associated with specific functions , such as the sensory , a motor and association regions . Although the left and right hemispheres are broadly similar in shape and function , some functions are associated with a particular side of the brain , such as language in the left and visual-spatial ability in the right . The hemispheres are connected by nerve tracts known as commisures , the largest being the corpus callosum .   The cerebrum is connected by the brainstem to the spinal cord . The brainstem consists of the midbrain , the pons , and the medulla oblongata . The cerebellum is connected to the brainstem by pairs of tracts known as peduncles . Within the cerebrum is the ventricular system of the brain , which consists of four interconnected ventricles in which cerebrospinal fluid is produced and circulated . Underneath the cerebral cortex , several important structures are located , including the thalamus , the epithalamus , the pineal gland , the hypothalamus , the pituitary gland , and the subthalamus ; the limbic structures , including the amygdala and the hippocampus ; the claustrum , the various nuclei of the basal ganglia ; the basal forebrain structures , and the three circumventricular organs .   The cells of the brain include neurons and supportive glial cells . There are more than 86 billion neurons in the brain and a more or less equal number of other cells . Brain activity is made possible by the interconnections of neurons that are linked together to reach their targets . These connections form various neural networks of neural pathways and circuits . The whole circuitry of the brain is driven by the process of neurotransmission .   The brain is protected by the skull , suspended in cerebrospinal fluid , and isolated from the bloodstream by the blood -- brain barrier . However , the brain is still susceptible to damage , disease , and infection . Damage can be caused by trauma , or a loss of blood supply known as a stroke . The brain is also susceptible to degenerative disorders , such as Parkinson 's disease , forms of dementia including Alzheimer 's disease , and multiple sclerosis . A number of psychiatric conditions , including schizophrenia and clinical depression , are thought to be associated with brain dysfunctions , although the nature of these is not well understood . The brain can also be the site of tumours , both benign and malignant . Malignant tumours mostly originate from sites outside the brain .   The study of the anatomy of the brain is neuroanatomy , while the study of its function is neuroscience . A number of different techniques are used to study the brain . Brain specimens from other animals , which may be examined microscopically , have been a traditional source of much information . Medical imaging technologies such as functional neuroimaging and electroencephalography ( EEG ) recordings are important techniques in studying the brain . Examining the medical history of people with brain injury has also provided great insight into the function of each part of the brain .

neg: Mahlon DeLong Mahlon R. DeLong is an American neurologist and professor at the Medical School of Emory University . His research has advanced the understanding and treatment of Parkinson 's disease , dystonia , tremor and other neurological movement disorders .   DeLong attended Stanford University ( AB 1962 ) , Harvard Medical School ( MD 1966 ) , completed his internship at Boston City Hospital and his residency training at Johns Hopkins Hospital in Baltimore , and subsequently joined the faculty of Johns Hopkins University . Since 1990 , he has been a member of the faculty at Emory University , where he has been the William Patterson Timmie Professor of Neurology since 1993 . He is a member of the Dana Alliance for Brain Initiative .   In 1968 , DeLong began five years of research training in the laboratory of Edward Evarts at the National Institutes of Health in Bethesda , Maryland . In 1971 , he and Russell T. Richardson did experiments with monkeys to find out first groups of neurons ( nucleus basalis ) , which are involved in the pathogenesis conditioned learning and they revealed the role played by the neurotransmitter acetylcholine .   At the NIH , DeLong recorded the reactions of single brain cells in a part of the brain called the basal ganglia . At that time , it was known that the basal ganglia were involved in movement , and were the part of the brain most significantly affected in Parkinson 's disease . However , little was known about how the basal ganglia affected movement , or how disease of the basal ganglia caused the movement disorders seen in Parkinson 's disease . In meticulous experiments over several years , DeLong measured the firing of specific cells in the basal ganglia of awake monkeys when they performed specific trained movements .   Based on this work , and the work of others , DeLong and his colleagues identified a series of separate circuits that connect the basal ganglia with the cerebral cortex and thalamus . These circuits allow parallel processing of emotions , thoughts , and movement .   In the 1980s , DeLong and his colleagues began to study monkeys with an experimentally-induced disease much like Parkinson 's disease . He discovered that neurons in a part of the basal ganglia called the subthalamic nucleus were firing excessively , and that destroying ( ablating ) the subthalamic nucleus greatly improved the symptoms .   Shortly thereafter , neurosurgeon Alim-Louis Benabid discovered that the same improvement could be achieved by placing a wire into the subthalamic nucleus , connecting it to a battery and delivering an adjustable high-frequency stimulation to the tip of the wire -- a technique called deep brain stimulation . Today , this technique is used to improve symptoms and the quality of life in patients with Parkinson 's disease who are not responding adequately to pharmacologic treatment . Ablation or deep brain stimulation of the subthalamic nucleus has transformed the lives of many people with Parkinson 's disease .   For his work in understanding the circuits connecting the basal ganglia to other parts of the brain , and in applying that knowledge to develop a technique that has eased the suffering of many people with Parkinson 's disease , DeLong was honored in 2014 with the Breakthrough Prize in Life Sciences .   The same accomplishments were recognized by his receipt ( with Benabid ) of the 2014 Lasker-DeBakey Clinical Medical Research Award .

neg: Cell cortex The cell cortex , also known as the actin cortex or actomyosin cortex , is a specialized layer of cytoplasmic protein on the inner face of the plasma membrane of the cell periphery . It functions as a modulator of plasma membrane behavior and cell surface properties . In most eukaryotic cells lacking a cell wall , the cortex is an actin-rich network consisting of F-actin filaments , myosin motors , and actin-binding proteins . The actomyosin cortex is attached to the cell membrane via membrane-anchoring proteins called ERM proteins and it plays a central role in cell shape control . The protein constituents of the cortex undergo rapid turnover , making the cortex both mechanically rigid and highly plastic , two properties essential to its function . In most cases , the cortex is in the range of 100 to 1000 nanometers thick .   In some animal cells , the protein spectrin may be present in the cortex . Spectrin helps to create a network by cross-linked actin filaments . The proportions of spectrin and actin vary with cell type . Spectrin proteins and actin microfilaments are attached to transmembrane proteins by attachment proteins between them and the transmembrane proteins . The cell cortex is attached to the inner ( cytosolic ) face of the plasma membrane in cells where the spectrin proteins and actin microfilaments form a mesh-like structure much like a fishnet except that it can be broken and reformed .   In plant cells , the cell cortex is reinforced by cortical microtubules underlying the plasma membrane . The direction of these cortical microtubules determines which way the cell elongates when it grows .

neg: Parkinson's disease Parkinson 's disease ( PD ) is a long-term degenerative disorder of the central nervous system that mainly affects the motor system . The symptoms generally come on slowly over time . Early in the disease , the most obvious are shaking , rigidity , slowness of movement , and difficulty with walking . Thinking and behavioral problems may also occur . Dementia becomes common in the advanced stages of the disease . Depression and anxiety are also common occurring in more than a third of people with PD . Other symptoms include sensory , sleep , and emotional problems . The main motor symptoms are collectively called `` parkinsonism '' , or a `` parkinsonian syndrome '' .   The cause of Parkinson 's disease is generally unknown , but believed to involve both genetic and environmental factors . Those with a family member affected are more likely to get the disease themselves . There is also an increased risk in people exposed to certain pesticides and among those who have had prior head injuries while there is a reduced risk in tobacco smokers and those who drink coffee or tea . The motor symptoms of the disease result from the death of cells in the substantia nigra , a region of the midbrain . This results in not enough dopamine in these areas . The reason for this cell death is poorly understood , but involves the build-up of proteins into Lewy bodies in the neurons . Diagnosis of typical cases is mainly based on symptoms , with tests such as neuroimaging being used to rule out other diseases .   There is no cure for Parkinson 's disease . Initial treatment is typically with the antiparkinson medication L-DOPA ( levodopa ) , with dopamine agonists being used once levodopa becomes less effective . As the disease progresses and neurons continue to be lost , these medications become less effective while at the same time they produce a complication marked by involuntary writhing movements . Diet and some forms of rehabilitation have shown some effectiveness at improving symptoms . Surgery to place microelectrodes for deep brain stimulation has been used to reduce motor symptoms in severe cases where drugs are ineffective . Evidence for treatments for the non-movement-related symptoms of PD , such as sleep disturbances and emotional problems , is less strong .   In 2015 , PD affected 6.2 million people and resulted in about 117,400 deaths globally . Parkinson 's disease typically occurs in people over the age of 60 , of which about one percent are affected . Males are more often affected than females . When it is seen in people before the age of 50 , it is called young-onset PD . The average life expectancy following diagnosis is between 7 and 14 years . The disease is named after the English doctor James Parkinson , who published the first detailed description in An Essay on the Shaking Palsy , in 1817 . Public awareness campaigns include World Parkinson 's Day ( on the birthday of James Parkinson , 11 April ) and the use of a red tulip as the symbol of the disease . People with parkinsonism who have increased the public 's awareness of the condition include actor Michael J. Fox , Olympic cyclist Davis Phinney , and late professional boxer Muhammad Ali .

neg: D-DOPA D-DOPA ( D-3 ,4 - dihydroxyphenylalanine ; dextrodopa ) is similar to L-DOPA ( levodopa ) , but with opposite chirality . Levo - and dextro - rotation reference a molecule 's ability to rotate planes of polarized light in either direction . Whereas L-DOPA is moderately effective in the treatment of Parkinson 's disease ( PD ) and Dopamine-responsive dystonia ( DRD ) by stimulating the production of dopamine in the brain , D-DOPA is biologically inactive .

neg: Serotonergic cell groups Serotonergic cell groups refer to collections of neurons in the central nervous system that have been demonstrated by histochemical fluorescence to contain the neurotransmitter serotonin ( 5-hydroxytryptamine ) . Since they are for the most part localized to classical brainstem nuclei , particularly the raphe nuclei , they are more often referred to by the names of those nuclei than by the B1-9 nomenclature . These cells appear to be common across most mammals and has two main regions in which they develop ; one forms in the mesencephlon and the rostral pons ( find articles/links ) and the other in the medulla oblongata and the caudal pons .   Nine serotonergic cell groups have been identified .

neg: Outline of the human brain The following outline is provided as an overview of and topical guide to the human brain :   Human brain -- central organ of the nervous system located in the head of a human being , protected by the skull . It has the same general structure as the brains of other mammals , but with a more developed cerebral cortex than any other , leading to the evolutionary success of widespread dominance of the human species across the planet .   While the emphasis below is on physical brain structure , functional aspects are also included . Mind concepts ( as in mind vs. body ) , and cognitive and behavioral aspects , are introduced where they have at least a fairly direct connection to physical aspects of the brain , neurons , spinal cord , nerve networks , neurotransmitters , etc. .

neg: 5-HT2C receptor agonist Serotonin 5-HT2 receptors are stimulated by monoamine neurotransmitters including serotonin , dopamine and norepinephrine . 5-HT2 receptor stimulation causes a buildup of intracellular inositol triphosphate and thereby an increase of cytosolic Ca2 + . 5-HT2C receptor agonists are attractive drug targets that have potential use in the treatment of a number of conditions including obesity , psychiatric disorders , sexual dysfunction and urinary incontinence .   The 5-HT2C receptors are one of three subtypes that belong to the serotonin 5-HT2 receptor subfamily along with 5-HT2A and 5-HT2B receptors . The development of 5-HT2C agonists has been a major obstacle , because of severe side effects due to a lack of selectivity over 5-HT2A and 5-HT2B receptors . Activation of 5-HT2A receptors can induce hallucinations , and the activation of 5-HT2B receptors has been implicated in cardiac valvular insufficiency and possibly in pulmonary hypertension .

neg: Frontostriatal circuit Frontostriatal circuits are neural pathways that connect frontal lobe regions with the basal ganglia ( striatum ) that mediate motor , cognitive , and behavioural functions within the brain . They receive inputs from dopaminergic , serotonergic , noradrenergic , and cholinergic cell groups that modulate information processing . Frontostriatal circuits are part of the executive functions . Executive functions includes following : selection and perception of important information , manipulation of information in working memory , planning and organization , behavioral control , adaptation to changes , and decision making . These circuits are involved in neurodegenerative disorders such as Alzheimer 's disease and Parkinson 's disease as well as neuropsychiatric disorders including schizophrenia , depression , obsessive compulsive disorder ( OCD ) , and attention-deficit hyperactivity disorder ( ADHD ) .

neg: Delta cell Delta cells ( δ-cells or D cells ) are somatostatin-producing cells . They can be found in the stomach , intestine and the pancreatic islets . In rodents , delta-cells are located in the periphery of the islets ; in humans the islet architecture is generally less organized and delta-cells are frequently observed inside the islets as well . In both species , the peptide hormone Urocortin3 ( Ucn3 ) is a major local signal that is released from beta cells ( and alpha cells in primates ) to induce the local secretion of somatostatin . Ghrelin can also strongly stimulate somatostatin secretion , thus indirectly inhibiting insulin release . Viewed under an electron microscope , delta-cells can be identified as cells with smaller and slightly more compact granules than beta cells .   D cells in the stomach contain CCKBR ( which respond to gastrin ) and M3 receptors ( which respond to Ach ) . Respectively , these receptors will increase somatostatin output and decrease somatostatin output from the D cells . VIP , vasoactive intestinal peptide , acts positively on D cells resulting in more somatostatin being released .   In the stomach , somatostatin acts directly on the acid-producing parietal cells via a G-protein coupled receptor ( which inhibits adenylate cyclase , thus effectively antagonising the stimulatory effect of histamine ) to reduce acid secretion . Somatostatin can also indirectly decrease stomach acid production by preventing the release of other hormones , including gastrin , secretin and histamine which effectively slows down the digestive process .