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Merrie Melodies

Merrie Melodies is an American animated series of comedy short films produced by Warner Bros. from 1931 to 1969, during the golden age of American animation. As with its sister series, Looney Tunes, it featured cartoon characters such as Bugs Bunny, Daffy Duck, Porky Pig and Elmer Fudd. Between 1934 and 1943, the Merrie Melodies series were distinguished from the black-and-white, Buddy or Porky Pig-starring Looney Tunes shorts by an emphasis on one-shot stories in color featuring Warner Bros.-owned musical selections. After Bugs Bunny became the breakout recurring star of Merrie Melodies and Looney Tunes went to color in the early 1940s, the two series lost their distinctions and shorts were assigned to each series more randomly. Merrie Melodies was produced by Harman-Ising Pictures from 1931 to 1933, Leon Schlesinger Productions from 1933 to 1944. Schlesinger sold his studio to Warner Bros. in 1944, the newly renamed Warner Bros. Cartoons continued production until 1963, it was outsourced to DePatie–Freleng Enterprises and Format Productions from 1964 to 1967, Warner Bros.-Seven Arts Animation resumed production for its final two years.

Three of the Merrie Melodies films won the Academy Award for Best Animated Short Film and another three have been inducted into the National Film Registry of the Library of Congress. In 2013, TV Guide ranked the Warner Bros. Cartoons the third Greatest Cartoon of All Time, one of only three film series to make the list. Producer Leon Schlesinger had produced one cartoon in the Looney Tunes series, based on music, its success prompted him to try to sell a sister series to Warner Bros, his selling point was that the new cartoons would feature music from the soundtracks of Warner Bros. films and would thus serve as advertisements for Warner Bros. recordings and sheet music. The studio agreed, Schlesinger dubbed the series Merrie Melodies. Walt Disney Productions had scored with their Silly Symphonies. Since cartoon production began with a soundtrack, animating a piece of music made it easier to devise plot elements and characters; the origins of the Merrie Melodies series begin with the failure of a live action series of musical shorts called Spooney Melodies, which featured popular songs of the day.

These shorts included segments with a popular artist singing along with appropriate background sequences. Warner Bros. wanted to promote this music because they had acquired the ownership of Brunswick Records along with four music publishers for US $28 million. Because of the success of their Looney Tunes series, Warner Bros. decided to develop a new series of animated musical shorts called Merrie Melodies. Hugh Harman and Rudolf Ising led the development, it was meant to be a series of musical cartoons that featured hit songs of the day those owned by Warner Bros. and featured in their musical films. In 1931, many of the shorts featured the orchestra of Abe Lyman, one of the most famous band leaders of his day; the first cartoon of the new Merrie Melodies series was Lady, Play Your Mandolin!, released in 1931. Ising attempted to introduce several characters in his Merrie Melodies films, such as Piggy and Goopy Geer. However, the series continued without any recurring characters; the shorts proved to be enormously popular with the public.

In 1932, a Merrie Melodies cartoon, entitled It's Got Me Again!, was nominated for the first Academy Award to be given for animation. When Harman and Ising left Warner Bros. in 1933, they took with them all rights to the characters they had created. Leon Schlesinger had to negotiate with them to keep the rights to the name Merrie Melodies, as well as for the right to use the slogan, So Long Folks, at the end of the cartoons. In 1934, Schlesinger produced his first color Merrie Melodies shorts, Honeymoon Hotel and Beauty and the Beast, which were produced in two-strip Cinecolor, their success convinced Schlesinger to produce all future Merrie Melodies shorts in color, using two-strip Technicolor. Looney Tunes continued in black and white until 1943. In 1936, the cartoons began to end with the slogan "That's all Folks!" which had only been used on the Looney Tunes series. The old slogan "So Long, Folks!" was abandoned at this time. The same year, Merrie Melodies began closing title sequences. By 1936, Disney's exclusivity on the three-color Technicolor process was lifted, allowing Merrie Melodies a full color palette for the first time, hence the use of the blue concentric rings for the rest of the 1935–36 season and the 1936–37 season.

The Warner Bros. shield was that year changed to cyan before changing back to red in 1938. Contractually, Merrie Melodies cartoons were obligated to include at least one full chorus from a Warner Bros. song. Warner Bros. requested that these songs be performed by name bands whenever possible, but this lasted only through the first few shorts. The policy annoyed the animators of Merrie Melodies, since the songs interrupted the cartoons' momentum and pacing. By 1939, the animators had been released from this obligation, the Merrie Melodies shorts

Exiled

Exiled is a 2006 Hong Kong action drama film produced and directed by Johnnie To, starring Anthony Wong, Francis Ng, Nick Cheung, Josie Ho, Roy Cheung and Lam Suet, with special appearances by Richie Jen and Simon Yam. The action takes place in contemporary Macau; the film made its premiere at the 63rd Venice International Film Festival, was in competition for the Golden Lion. In 1998 Macau, former mobster Wo lives with his wife and his newborn child in a nondescript apartment, having turned over a new leaf, but vengeful mob boss Fay —whom Wo once tried to assassinate—has dispatched a pair of ageing hitmen to cut that peaceful existence short. Once arrived, killers Blaze and Fat find a second pair of hitmen and Cat, who are determined to protect Wo. After a brief showdown, the whole group comes to an uneasy truce, lay their weapons down and bond over dinner— after all, these men grew up together in the same gang. Reunited and hungry for another score, they visit a fixer called Jeff, who gives the gang the job of killing a rival boss, Boss Keung, as well as telling them about the location of a large quantity of gold being transported for a corrupt official.

Wo makes the gang promise that if anything happens to him, his son will be looked after. That night the friends find Boss Keung in a restaurant. Boss Fay recognising Blaze sitting in the restaurant chastises and humiliates him for not killing Wo, culminating in Fay shooting Blaze; however unbeknownst to Fay, Blaze survives. Wo, seeing this, opens fire. A gunfight erupts in the restaurant with Fay Keung in the arm; the two bosses come to an agreement to share territory and profits, further agreeing to kill the gang of friends. Having narrowly escaped the restaurant shootout the friends decide to take a shot Wo to an underground clinic for medical assistance. After negotiating a price, the doctor operates removing the bullets from Wo. However, as he is sewing up Wo's wound, there is a loud banging at the door. Having heard this the remainder of the waiting friends hide in the doctor's flat; the door is answered and both Fay and Keung burst in seeking help for their injuries sustained in the restaurant shootout.

Fay pushes orders the doctor to tend to his wound first. Meanwhile, Keung comes across a hiding Fat. Realizing that they have been found, the gang begin to dispatch the bosses' henchmen. Meanwhile, Wo wakes up and gets to his feet to escape before collapsing; the rest of the friends not knowing where Wo has got to, make an exit down the back of the apartment. However whilst escaping across the back courtyard, Boss Fay throws Wo from a high window and pins down Wo's friends preventing any rescue attempt; the gang try to retrieve their critically injured but still alive friend but Fay still shoots at them and manages to shoot Wo. Quick thinking Fat seeing that his friend has come to rest on some tarpaulin pulls Wo to safety and the gang escape. Now in the car Wo knowing he is near death, asks to be taken back to his wife and son. Wo dies shortly after. Handing Wo's body over to his wife, she demands to know what has happened and in her grief opens fire on Blaze and Tai who run away. Jin thinks better of it.

She instead makes a funeral pyre for Wo. She sets fire to Wo and the flat and leaves with her son; the reduced gang leave the city in search of the gold. After coming across the guarded convoy carrying the gold, they flip a coin to decide whether to hijack it or not; the coin comes up tails meaning. After carrying on down the road however the come across the convoy being ambushed by another gang, they witness all the police officers bar one crack-shot being killed. The friends decide to help the officer by dispatching the rest of the gang; the friends appreciating the policeman's sharp shooting decide to split the gold with him and drive off to a hidden dock to transport the gold to the mainland and a new life. Meanwhile, back in the city, Jin still furious about the death of her husband goes looking for the friends, asking many people until she is recognised by the fixer Jeff who in turn contacts his boss, Boss Fay. Fay with a captured Jin calls a gloating Blaze, informed of the situation, he is told to meet Fay at midnight otherwise Jin and her son will be killed.

Determined to protect Jin after Wo's death, the friends agree and leave the officer at the dock with the gold telling him they will return by dawn. Once at the meeting place the four friends are confronted by Jin, whom Fay allows to shoot Blaze in revenge; however Blaze is again hit in the chest. Tai steps in, throwing a bag of gold at Fay's feet telling him that he can have it all if Fay lets them all go. Fay tells them Blaze must stay to face the consequences of not following orders. Blaze agrees to this deal and the remainder of the friends leave with Jin. However, as they leave, Tai tells her to drive there. With Jin safe the outnumbered friends open fire. In the resulting gunfight all are killed including Boss Keung; as the friends lie dying they all smile knowing. Anthony Wong as Blaze Francis Ng as Tai Nick Cheung as Wo Josie Ho as Jin, Wo's wife Roy

NUDT15

Nudix hydrolase 15 is a protein that in humans is encoded by the NUDT15 gene. This gene encodes an enzyme. Members of this superfamily catalyze the hydrolysis of nucleoside diphosphates, including substrates like 8-oxo-dGTP, which are a result of oxidative damage, can induce base mispairing during DNA replication, causing transversions; the encoded enzyme is a negative regulator of thiopurine toxicity. Mutations in this gene result in poor metabolism of thiopurines, are associated with thiopurine-induced early leukopenia. Multiple pseudogenes of this gene have been identified. NUDT15 germline variants have been linked to clinical usage of thiopurines in acute lymphoblastic leukemia as well as inflammatory bowel diseases to avoid thiopurine-induced leukopenia; these variants exhibit ethnicity-specific. Rare functional variants singletons in this gene have been identified to be related to thiopurine-induced myelotoxicity, suggesting the whole gene screening should be taken to determine the initial dosage using of thiopurine.

Overview of all the structural information available in the PDB for UniProt: Q9NV35 at the PDBe-KB. This article incorporates text from the United States National Library of Medicine, in the public domain