12 foot dinghy, The Alternative Designs, The Irish Championships
The following year the event in Dun Laoghaire harbour, which was part of the National Heritage Week, was sailed in light weather, and showed that the DBSC boat was capable of pointing higher upwind, but being considerably slower downwind. The Irish championship winner was the DBSC 12 Sgadan owned by David Sarratt and crewed by Gail Varian.


12 foot dinghy, The Alternative Designs, The Irish Championships
In 2018 George Miller in 'Pixie' repeated his 2015 win despite completing race three with a jury rig. Miller dominated again in 2019.


12 foot dinghy, The Alternative Designs, The Irish Championships
in 2021 the 12 foot dinghies were joined by an earlier (1896) 12 foot design, The Bray Droleen, for the Irish Championships. The Droleen is an American style catboat designed by William Ogilvy.


12 foot dinghy, The Alternative Designs, Clinkerfest
In 2020 Athlone Yacht Club/ Lough Ree Yacht Club planned to celebrate 250 years of leisure sailing and one of the chief events was to be 'Clinkerfest', a celebration of the Clinker built boats introduced in Ireland by the Vikings 1000 years ago. Racing for International 12 footers, Water Wags, IDRA 14s, Mermaids, Colleens and of course Shannon ODs. Was intended. The event was postponed for one year in compliance with Covid regulations.


12 in a Box
12 in a Box is a 2007 British independent comedy film written and directed by John McKenzie. The film premiered at the 2007 Zurich Film Festival.


12 in a Box, Plot
12 in a Box sees twelve people attend what they think is a school reunion lunch but when they get there they discover that, as part of the last wish of a dead classmate, they will inherit £1,000,000 each if they can all stay together in the house for 96 hours. With one of the participants due to be married and another dropping stone dead on the first day, they have their work cut out to go the distance.


12 in a Box, Release
The film was given a limited European release in 2007 and had its US premiere in Boston in 2009. Despite being a British film with some notable names in the cast, it was not released in the UK until March 2013.


12 in a Box, Critical response
The film received the Audience Award at the 2007 Zurich Film Festival, Indie Spirit Best Storyline Award at the 2009 Boston International Film Festival and the Best Film Award at the 2009 LA British Film Festival. The LA Campus Circle graded the film A- and called it "smart, funny and surprising without being pretentious or hackneyed. There are few dull moments, and it actually succeeds in pulling off the twists." The film was also praised by The Film Review and CineVue. The Guardian, however, gave it a poor review, as did the Radio Times and the Daily Express.


12 in a Box, Criticism
The DVD was released in 2013  marketed under Miranda Hart's name due to her fame; Hart only makes a brief appearance, however, and her screen time is only 5 minutes.


12 let Oktyabrya
12 let Oktyabrya (Russian: 12 лет Октября) is a rural locality (a settlement) in Kargashinskoye Rural Settlement of Sasovsky District, Russia. The population was 9 as of 2010.


12 let Oktyabrya, Geography
12 let Oktyabrya is located 11 km northwest of Sasovo (the district's administrative centre) by road.


12 m2 Sharpie
The 12 m2 Sharpie was designed in 1931 by the Kröger Brothers in Warnemünde, Germany. The peak of the class was in the 1956 Melbourne Olympic Games. To this day, the original design has been preserved, and the class is sailed competitively in the UK, The Netherlands, Germany, and Portugal. The European Championships are rotated between these four countries every year.


12 m2 Sharpie
The term 'Twelve Square Metre' evolves from the original sail area, though on modern sharpies due to modern sail designs has now reached to around sixteen square metres.


12 m2 Sharpie
Past Australian champions to have passed through the ranks include Sir James Hardy, John Cuneo, Rolly Tasker and John Bertrand. Rolly Tasker won Australia's first sailing medal at the 1956 Olympic Games in Melbourne when he and John Scott won a silver medal in their 12 m2 Sharpie.


12 m2 Sharpie
The 12 m2 Sharpie is one of the Vintage classes for the 2018 Vintage Yachting Games.


12 m2 Sharpie
There are still a small number of original sharpies in Australia and Brasil, though they have not been sailed competitively on International level since the 1960s. In Australia, the original 'heavyweight' Sharpie has now evolved into the lightweight Australian Sharpie.


12 m2 Sharpie
When racing in a mixed fleet, the 12 m2 Sharpie has a Portsmouth number of 1026.


12 mm Lefaucheux
The 12mm Lefaucheux is a metallic center-fire cartridge. It was originally created as a rimless pinfire cartridge using black powder employed by the French navy on the Lefaucheux M1858 revolver. Later adapted for center-fire by the French Army in 1873 for use on the MAS 1873 revolver.


12 mm Lefaucheux, Overview
Originally, the 12 mm, was a classic Lefaucheux cartridge, with a side pin from its introduction in 1858 until 1873, when it was adapted and became a rimmed center-fire cartridge for use in the MAS revolver 1873-1874 then used by the French Army.


12 mm Lefaucheux, Features
These are the characteristics of the '12 mm Lefaucheux' cartridge:


12 mm Lefaucheux, Features
In these markings, the initials "G. E" referring to the manufacturer "Ernest Gaupillat", and the other letter and digits referring to the batch (probably place and date).


12 mm caliber
This is a list of firearm cartridges which have bullets in the 12 millimetres (0.47 in) to 12.99 millimetres (0.511 in) caliber range.


12 mm caliber
Some measurements are in millimetres, others are in calibers, which are measured in inches.


12 mm caliber, Rifle cartridges
'Note: The .50 Sharps, Winchester and US Government cartridges are actually of 13 mm caliber


12 month rule
In the field of taxation in the United States, the 12 Month Rule refers to the capitalization of property or assets that provide only short-term benefits. The 12 Month Rule makes it unnecessary to capitalize the cost of purchase or production of anything with a useful life of less than a year, although it is not without exception. Prop. Reg


12 month rule
. 1.263(a)-2(d)(4)(i) serves to codify the 12 Month Rule and the generally accepted view that capitalization is only required for costs related to the purchase or production of fixed assets that will continue to provide a benefit over the course of several years, or at least for a time significantly longer than the taxable year.


12 oz. Mouse
12 oz. Mouse is an American surreal humour and psychological thriller adult animated television series created by Matt Maiellaro for Cartoon Network's late-night programming block, Adult Swim. The series revolves around Mouse Fitzgerald, nicknamed "Fitz" (voiced by Maiellaro), an alcoholic mouse who performs odd jobs so he can buy more beer. Together with his chinchilla companion Skillet, Fitz begins to recover suppressed memories that he once had a wife and a child who have now vanished. This leads him to seek answers about his past and the shadowy forces that seem to be manipulating his world.


12 oz. Mouse
In producing the series, Maiellaro crudely designed the characters as a cost-cutting measure; the series is animated by Radical Axis. He intended for the series to lack continuity starting from the pilot but established a serial format after starting the second episode. He had constructed an ending for the series as well as a detailed map of characters; however, the series finale concluded differently from planned. Maiellaro cast people around his office for the characters, starring himself as the protagonist and Nine Pound Hammer vocalist Scott Luallen as the voice of Roostre; the band also performs the opening theme.


12 oz. Mouse
The pilot episode for 12 oz. Mouse, "Hired", premiered on June 19, 2005. The series became a regular staple of Adult Swim's lineup on October 23 of that year and originally ended on December 17, 2006. A stand-alone webisode was released online on May 16, 2007. Critical reception was polarized; some praised the series' experimental nature, while others felt confounded by it.


12 oz. Mouse
In 2018 a double-length special, entitled "Invictus", aired on October 14th and it was announced that 12 oz. Mouse was also revived as a series. The third season, consisting of 11 episodes, premiered on July 20 and ended on July 31, 2020. The ending credits of both "Invictus" and the season 3 episodes feature a song by Amaranthe.


12 oz. Mouse
In February 2021, it was revealed that the show would not be picked up for a fourth season.


12 oz. Mouse, Premise
The show revolves around a mouse named Mouse Fitzgerald (voiced by Matt Maiellaro), nicknamed "Fitz", who is fond of beer and caught in a world of espionage, love, and the delights of odd jobs. The show employs a serial format, and its ongoing storyline developed from absurdist comedy to include mystery and thriller elements. Fitz begins to recover suppressed memories that he once had a wife and a child who have now vanished. This leads him to seek answers about his past and the shadowy forces that seem to be manipulating his world.


12 oz. Mouse, Premise
Fitz suspects there is a sinister conspiracy which appears to revolve around fields of "asprind [sic]" pills beneath the city, and Shark (Adam Reed), Clock, and Rectangular Businessman's (Kurt Soccolich) attempt to control the nature of time and reality. Fitz and Skillet receive help from Liquor (Matt Harrigan), Roostre (Scott Luallen), Stoned Peanut Cop (Nick Weidenfeld) and others as they engage in gun battles, blow things up, and try to understand cryptic hints. The show also sometimes contains surreal "subliminal" images that flash across the screen during key plot moments, including skulls, mustached snake beasts and people screaming.


12 oz. Mouse, Premise
The series concludes with the revelation that Fitz has been kidnapped and placed into a simulation by the Shadowy Figure. He is about to be killed by Shark and the Rectangular Businessman, in their true forms outside the simulation, when he is rescued by the true form of Peanut Cop and a nurse who works in the simulation chamber. They kill Shark and Rectangle Businessman, but it is unknown if they are truly dead because the simulation in which most of the show takes place is probably taking place in another simulation.


12 oz. Mouse, Premise
One of the purposes of the simulation seen in most of the show was to extract information from Fitz. The conclusion to episode 20 is ambiguous as to whether or not it is actually the end of the series, as some aspects of the plot remain unresolved – Golden Joe says "I thought this was done," to which Fitz replies, "I thought so too. I guess we're not."


12 oz. Mouse, Premise
One webisode was made in 2007, showing Fitz and his friends escaping the city to live in a desert. Golden Joe is carried away by birds, while later one night, Peanut Cop mysteriously disappears. Fitz and Skillet later meet a woman, Lee, who turns out to be a werewolf. Their fate at the end of the episode was unknown.


12 oz. Mouse, Premise
In 2018, a half-hour special episode aired, which continued the story. Fitz, now with a mustache and suffering from amnesia, is shown to be living in a new city during an unspecified amount of time after the original finale. Shark and Square Guy have returned somehow, and are trying to kidnap Fitz so they can return to the "real" world with the help of exterminator bee, Buzby (Dana Snyder). Skillet, Roostre, Peanut Cop, Golden Joe, and The New Guy (Mike Lazzo) must find and escape the simulation with Fitz before Shark and Square Guy do.


12 oz. Mouse, Development, Production
According to Maiellaro, the series was pitched as a table read to the network. He jokingly stated that they accepted it after claiming that production costs would total "five dollars and will take some of the paper sitting in the copier." Maiellaro borrowed inspiration from surrealism and the films of David Lynch. He intended for the series to lack continuity starting from the pilot, but established a serial format after starting to work on the second episode.


12 oz. Mouse, Development, Production
He had constructed an ending for the series as well as a detailed map of characters; however, the series finale concluded differently from planned. In November 2006, Maiellaro mentioned the possibility of continuing the series with webisodes, and he wrote five additional scripts for ending the series, but finally, he only produced one webisode, entitled "Enter the Sandmouse".


12 oz. Mouse, Development, Production
Radical Axis provided animation for the series using Final Cut Pro. Described as "lo-fi animation", Maiellaro crudely designed the characters as a cost-cutting measure, with the exception of Amalockh, a many-armed monster summoned in the season two episode "Corndog Chronicles", which was drawn and animated by Todd Redner at the studio, and Shark, which was borrowed from the Space Ghost Coast to Coast episode "Kentucky Nightmare".


12 oz. Mouse, Development, Production
In a behind-the-scenes clip of the show, Maiellaro explained that to animate the series, he would first grab a nearby sheet of copy paper, draw something, and then scan it, followed by him sending the file to an animator. Rhoda, a character from the series, was drawn on the back of a script page for Perfect Hair Forever. A scan of the paper revealed the textual contents behind it, which Maiellaro decided to leave in.


12 oz. Mouse, Development, Cast
Maiellaro cast people around his office to voice the characters. He provides the voice of the protagonist, Mouse Fitzgerald. He originally only gave the scratch dialogue for the character during the production of the pilot episode but chose himself to voice Mouse regularly after hearing his lines assembled in the final cut. Kurt Soccolich was chosen by Maiellaro to voice Rectangular Businessman, who "already had that sort of smooth arrogance in his voice", making him a "perfect" fit for him. Matt Harrigan was selected to voice Liquor, who is "always looking to make light of a situation", according to Maiellaro.


12 oz. Mouse, Development, Cast
Nick Weidenfeld provides the voice of Peanut Cop; Melissa Warrenburg portrays an annoying woman in a green sweater, who Maiellaro dubs "Robogirl". Bonnie Rosmarin voices Man/Woman, picked for what Maiellaro stated is a "pouty, stand-offish quality" in her delivery. Nick Ingkatanuwat voices The Eye and Adam Reed plays Shark. Vocalist of Nine Pound Hammer Scott Luallen voices Roostre; the band also composed the opening theme song for the series. Golden Joe is voiced by Vishal Roney; after hearing his first take on the character, Maiellaro explained that he was left unable to write any of his lines. He proceeded to only provide the basic structure of his lines in the script, instructing him to retroscript the rest.


12 oz. Mouse, Development, Title sequence and music
Maiellaro spent three weeks working with Ingkatanuwat on putting together the set for the opening title sequence. The set was filmed with a motion control camera and was inserted with miniature explosives and smoke bombs for special effect. Nine Pound Hammer composed the opening theme song; Maiellaro sought a song representing the "carefree" lifestyle of Mouse who "does things like drive drunk, film porno and shoot guns." Maiellaro, who plays the electric guitar in his free time, also composed the song "F-Off", featured in both the first episode and in "Auraphull", which he wrote while working on Space Ghost Coast to Coast. Swedish heavy metal band Amaranthe performed the credits theme song for the 2018 special, "Invictus".


12 oz. Mouse, Development, Revival
The June 14, 2018 episode of the Adult Swim streaming series Development Meeting featured a new clip from 12 oz. Mouse, which featured Seth Green as Fitz, hinting at a return to the series. It was later announced on September 18 of that year that the series would return for a half-hour special entitled "Invictus", which aired a month later on October 14. On the day of the special's airing, another announcement was made that the series would return for an 11-episode third season which aired in late July 2020. On March 31, 2020, the third season premiere aired unannounced at 2:45 AM EST with many other new episodes from Adult Swim shows as part of Adult Swim's annual April Fools Prank. The whole third season premiered on July 20, 2020, and ended on July 31st.


12 oz. Mouse, Episodes
The pilot episode for 12 oz. Mouse, "Hired", premiered in June 2005 and became a regular series in the Adult Swim lineup in October 2005. An Adult Swim bumper shown with the sixth installment claimed that twenty additional episodes were being produced and taunted viewers who had complained they couldn't understand the absurdist presentation. On December 31, 2005, a marathon of the series aired, replaying all six episodes followed by the premiere of the then-unfinished seventh episode "Adventure Mouse".


12 oz. Mouse, Episodes
The second season aired on Adult Swim on Monday mornings at 12:45 a.m. EST from September 24, 2006 to December 17, 2006. On May 16, 2007, the 21st episode, entitled "Enter the Sandmouse", premiered as a webisode. On October 14, 2018, a half-hour special titled "Invictus" premiered on TV after having been released online two days earlier. Simultaneously, Adult Swim announced the series would be returning for a third season. The third season premiered unexpectedly on March 31, 2020 as part of that year's Adult Swim's April Fools Prank.


12 oz. Mouse, International broadcast
In Canada, 12 oz. Mouse previously aired on Teletoon's Teletoon at Night block, and currently airs on the Canadian version of Adult Swim.


12 oz. Mouse, Reception, Ratings
The season two episodes, "Auraphull" and "Meat Warrior", were respectively seen by 460,000 and 431,000 viewers upon broadcast. In addition, the episodes ranked as the thirteenth and twelfth most-watched episodes aired by the network for the week of October 23, 2006, also respectively.


12 oz. Mouse, Reception, Critical reception
The series has received generally positive critical reception; About.com's Nancy Basile gave the series four out of five stars, opining that the series is "what Adult Swim should be ... experimental, but in a cheap, simple, not-trying-to-be-cool way." She found the crude animation "refreshing" but joked that the series "can kill" viewers not used to the slow pace. Writing for AOL TV, Adam Finley regarded the show as "the most simplistically drawn of all the Adult Swim shows, and yet the most complex in terms of story." He contrasted it with other Williams Street productions, finding it "instead unravels slowly, revealing a little bit more of what's underneath the surface while also piling on more and more questions." Rob Mitchum of Pitchfork Media called it "the asymptote of the block's crude style".


12 oz. Mouse, Reception, Critical reception
Justin Heckert of Atlanta magazine opined that "the animation and art look like they were done by daycare students".


12 oz. Mouse, Other appearances
The hip hop duo Danger Doom have produced a song inspired by 12 oz. Mouse entitled "Korn Dogz" from their EP Occult Hymn. The song uses audio clips from the episode "Rooster", with the line "Corn dogs for the pickin'" being recited by Danger Doom's MC MF Doom and Mouse Fitzgerald. A scene from the episode "Sharktasm" is visible in Aqua Teen Hunger Force Colon Movie Film for Theaters.


12 oz. Mouse, Home release
A DVD release of the first 2 seasons was released February 29, 2008 (leap year), exclusively on the Williams Street shop. The DVD cover depicts Leonardo's The Last Supper with the series' characters replacing Christ and the twelve apostles. However, under a black light, the cover depicts the skeletons of the characters, as well as letters and symbols which make out an email address. The series is presented as a single, continuous movie, with newly produced footage bridging the gaps between episodes. It also features production footage, new music, the episode "Auraphull" in its entirety and collected fan art.


12 points of the Hungarian Revolutionaries of 1848
The 12 points (Hungarian: 12 pont) were a list of demands written by the leaders of the Hungarian Revolution of 1848.


12 points of the Hungarian Revolutionaries of 1848, History
On the morning of March 15, 1848, revolutionaries marched around the city of Pest, reading Sándor Petőfi's Nemzeti dal (National Song) and the 12 points to the crowd (which swelled to thousands). Declaring an end to all forms of censorship, they visited the printing presses of Landerer and Heckenast and printed Petőfi's poem together with the demands. A mass demonstration was held in front of the newly built National Museum, after which the group left for the Buda Chancellery (the Office of the Governor-General) on the other bank of the Danube. When the crowd rallied in front of the Imperial Governing Council, the representatives of Emperor Ferdinand agreed to sign the 12 points.


12 posyolok
12 posyolok (Russian: 12 посёлок) is a rural locality (a settlement) in Shatura Urban Settlement of Shatursky District, Russia. The population was 159 as of 2010.


12 posyolok, Geography
12 posyolok is located 269 km northwest of Shatura (the district's administrative centre) by road.


12 to the Moon
12 to the Moon is a 1960 independently made American black-and-white science fiction film, produced and written by Fred Gebhardt, directed by David Bradley, that stars Ken Clark, Michi Kobi, Tom Conway, and Anna-Lisa. The film was distributed in the U.S. by Columbia Pictures as a double feature with either Battle in Outer Space or 13 Ghosts, depending on the local film market.


12 to the Moon
12 to the Moon was novelized by Fred Gebhardt under the pen name Robert A. Wise and published in 1961. Gebhardt also wrote the film's original story.


12 to the Moon, Plot
Earth's International Space Order prepares for its first manned landing on the Moon, with the goal of claiming it as "international territory". The crew of Lunar Eagle 1 comprises 12 people from around the world, 10 men and two women, all scientists with different specialties, accompanied by a small menagerie, including two cats. The spaceship is commanded by American John Anderson (Ken Clark).


12 to the Moon, Plot
Historical and international tensions flare up during the flight. Feodor Orloff (Tom Conway), a Russian, struts about, annoyingly claiming that all scientific advancements were invented by the Soviets. Israeli David Ruskin (Richard Weber) warns Feodor that the USSR would be unwise to attempt to dominate Israel, as it has his native Poland. David admires fellow astronaut Erich Heinrich (John Wengraf), unaware that Erich's father was the Nazi responsible for murdering David's family during the Holocaust.


12 to the Moon, Plot
After a dangerous 27-hour flight, Lunar Eagle 1 lands and the crew begin their exploration of the Moon. Sigrid Bomark (Anna-Lisa) and Selim Hamid (Muzaffer Tema) find an air-filled cave and after shedding their space helmets, they kiss passionately. As they walk hand-in-hand deeper into the cave, its opening is suddenly sealed by impenetrable ice.


12 to the Moon, Plot
The others discover gold and minerals, but when they fire a mortar into a rock formation, liquid begins bubbling out. An excited Feodor rushes over and sticks his hands into the flow, and he is badly burned. On the way back to their spaceship, a crew member sinks to his death in lunar quicksand. John tries unsuccessfully to save him and is almost pulled under.


12 to the Moon, Plot
Inside Lunar Eagle 1, a machine begins printing out hieroglyphics. Surprisingly, Hideko Murata (Michi Kobi) can read them. It is a message from "The Great Coordinator of the Moon", who orders the crew to leave at once. The message also states that the emotionless Moon-beings live underground and fear that the Earthlings will "contaminate our perfect form of harmony". Sigrid and Salim are being studied because the Moon-beings are unfamiliar with "love". They and "all your kind" will be destroyed "if love turns to evil". The Moon-beings also demand that the expedition's cats, brought as an experiment to see if they could procreate on the Moon, be left behind. They find the felines as interesting as people.


12 to the Moon, Plot
Erich has a heart attack during Lunar Eagle 1's blast off. As he babbles on half-conscious, David learns that Erich's father was the Nazi who killed David's family. However, when David learns that Erich has disowned his family and devoted his life to trying to make amends for his father's crimes, they become friends.


12 to the Moon, Plot
Near Earth, the crew witnesses "the big freeze", a gigantic freezing cloud controlled from the Moon, which encases all of Canada, the U.S., and Mexico in thick ice.


12 to the Moon, Plot
John decides to drop "atomic bomblets" into the volcano Popocatepetl in order to trigger a huge eruption to thaw out North America. Etienne Martel (Roger Til) sabotages the bomblets, revealing himself to be a French communist. He assumes that Feodor would also want to keep America frozen in order to advance international communism's quest for world domination. Feodor doesn't. He and Etienne fight, Feodor calls to John for help, and when Etienne unfairly pulls out a knife, John knocks the weapon out of his hand, while knocking him down. Feodor repairs the bomblets.


12 to the Moon, Plot
Erich and David fly a suicide mission to drop the bomblets from their spaceship's smaller space taxi. Popocatepetl erupts and North America begins to thaw. Another message from the Moon says that the Moon-beings now realize that Earthlings are honorable and peaceful, and that the North Americans were put into suspended animation before the big freeze, so no-one has been harmed. Moreover, Earthlings will be welcomed to the Moon whenever they return.


12 to the Moon, Plot
Following the great thaw, Lunar Eagle 1's triumphant crew prepare to land.


12 to the Moon, Production
12 to the Moon was in production during April-June 1959 at Hollywood's California Studios. The actual filming took seven or eight days, and the entire film was budgeted at $150,000. Although it wasn't released theatrically for another year, the American Film Institute notes that "According to an Oct 1959 HR [The Hollywood Reporter] news item, Columbia purchased the independent production in Aug 1959, intending to rush it into release to capitalize on the topicality of a space launch". Director David Bradley fought over the reediting of the film.


12 to the Moon, Release
12 to the Moon premiered in Los Angeles on June 22, 1960. Columbia Pictures handled the theatrical release in the US and the UK during the same year. It opened in Mexico on February 23, 1961 and was also shown in Australia at an unspecified date.


12 to the Moon, Release
The film was syndicated to American television in September, 1963, as part of Screen Gems' "X" package of horror and science fiction films.


12 to the Moon, Reception
1960 film critics generally found the film to be, in the words of British film critic Phil Hardy, "a decidedly minor offering, the presence of [DeWitt] Bodeen (writer of Cat People, 1942) and [John] Alton, one of Hollywood's unsung cinematographic geniuses, notwithstanding". "Kobe", writing in the June 22, 1960 issue of Variety, called 12 to the Moon a 'Lower-half science-fantasy item in which a dozen good eggs from earth tangle with some righteous, but misdirected, luna-tics. Timely, but crude and cliché-ridden". "Kobe", however, also praised Alton's camerawork.


12 to the Moon, Reception
The anonymous reviewer in BoxOffice referred to the film as "A modest science fiction programmer [which] will satisfy the youngsters and the action fans who delight in stories of rocketships to the moon". The magazine gave the film a rating of "fair" on its poor-to-very-good scale.


12 to the Moon, Reception
According to Bill Warren, the American science fiction film critic and historian, the Monthly Film Review said the film was a "juvenile piece of hokum" with "only its special effects and weird lunar landscape to recommend it", although Kinematograph Weekly in the UK found more merit, calling 12 to the Moon "Extravagant and intriguing [with a] fascinating subject, sound acting [and] resourceful technical presentation".


12 to the Moon, Reception
While modern-day critics have called the film "extremely strange and unpredictable", relatively little appears to have been written about the international status of the astronauts and the bearing it has on the plot. American film critic Gary Westphal points out that the "unusually large crew of twelve [is] said to represent twelve different countries": Brazil, France, Germany, United Kingdom, Israel, Japan, Nigeria, Poland, Russia, Sweden, Turkey, and the US, which indicates that the journey is motivated primarily by a desire "to prevent national disputes arising over the moon in particular and, one infers, other subjects in general". However, as Warren points out, "each person acts in accordance with national stereotypes and has virtually no other characterization".


12 to the Moon, Reception
Modern critics have also taken the film to task for its special effects. For example, Westphal writes that the space helmets have no visors, but each is instead equipped with an "invisible electromagnetic ray screen" that protects the astronauts' faces. He speculates that the obviously missing visors were perhaps not noticed until late in the filming and that a scene which explains the ray screens was inserted prior to the film's release, before audiences could wonder about it.


12 to the Moon, Reception
Bryan Senn, also an American critic, notes that "The effects are minimal and substandard, consisting mainly of the same shot of a rocket traveling through space used over and over again (and it's not even a convincing shot - the stars shine right through the transparent-looking ship)", although he calls the Moon set "eerie and effectively alien, with its cracks, weird shadows, and smoke seeping from mysterious holes". Warren points out that the Earth-saving eruption of Popocatepetl is "depicted by stock footage of solar prominences" that bear little resemblance to real volcanic eruptions.


12 to the Moon, Reception
Modern critics are also bothered by the narrative development of the film. Westphal says that "Few films ... begin as soberly, and end as absurdly, as 12 to the Moon. The film's first thirty minutes promise an internationalized update of Destination Moon [1950], while later events rival a Flash Gordon serial". Senn agrees that the film is disappointing, noting that "What starts out as a fairly intelligent and progressive space-travel film ... quickly degenerates into a juvenile, simplistic space opera. Admittedly, space operas have their place, but 12 to the Moon fails to deliver even a single aria, much less the whole opera".


12 to the Moon, Home video
12 to the Moon was released in 2010 on Region 1 DVD by Sony Home Entertainment. Mill Creek Entertainment released it again in 2015 on Region 1 DVD as part of its Vintage Sci-Fi 6 Movie Collection. Shout! Factory followed suit in 2016 with a Region 1 DVD release of Mystery Science Theater 3000's voice-over commentary lampooning the film.


12 to the Moon, Mystery Science Theater 3000
12 to the Moon was featured in episode #524 of Mystery Science Theater 3000, along with the short Design for Dreaming. The episode debuted February 5, 1994, on Comedy Central. The Amazing Colossal Episode Guide calls the film "a static Fifties vision of space travel". The episode's interstitial host segments feature the constantly singing Nuveena, the Woman of the Future, a character played by Bridget Jones, taken from the Design for Dreaming short that accompanied the MST3K episode.


12 to the Moon, Mystery Science Theater 3000
12 to the Moon did not make the Top 100 List voted upon by MST3K's Season 11 Kickstarter backers. However, writer Jim Vogel was much more enthusiastic about the episode, ranking it #34 out of the 191 total MST3K episodes. Vogel was entertained by 12 to the Moon's shortcomings, saying, "The crew of 12 international astronauts are wonderfully stupid, in a way that only movie astronauts can be. ... It’s so earnestly stupid that it’s impossible to not be charmed by it".


12 to the Moon, Mystery Science Theater 3000
12 to the Moon was included as part of the Mystery Science Theater 3000, Volume XXXV DVD collection, released by Shout! Factory on March 29, 2016. The collection includes a documentary on the making of the film, You Are There: Launching 12 to the Moon. The documentary is narrated by film historian Jeff Burr. The other episodes in the four-disc set include  Teenage Caveman (episode #315), Being from Another Planet (episode #405), and Deathstalker and the Warriors from Hell (episode #703).


12 éxitos para 2 guitarras flamencas
12 éxitos para 2 guitarras flamencas (12 Hits for 2 Flamenco Guitars) is the third of three collaboration albums between Paco de Lucía & Ricardo Modrego.


12 éxitos para 2 guitarras flamencas, Personnel
Paco de Lucía – Flamenco guitarRicardo Modrego – Flamenco guitar


12 Şubat Stadium
12 Şubat Stadium is a multi-purpose stadium in Kahramanmaraş, Turkey. It is currently used mostly for football matches and is the home ground of TFF Second League team Kahramanmaraşspor.


12 Şubat Stadium
The stadium was built in 1970 and currently holds 15,000 people.


12!
12! is an album by saxophonist Sonny Stitt recorded in 1972 and released on the Muse label.


12!, Reception
AllMusic reviewed the album stating "this album is also one of the saxophonist's most rewarding recordings".


12" Collection
12" Collection is Rick Astley's first compilation album, released in 1999. It was re-released with a different track listing in 2006.


12" Collection, Track listings, 1999
All tracks written by Stock, Aitken & Waterman except track 2 by Rick Astley


12" Collection and More
12" Collection and More is compilation album released by the funk/R&B group Cameo in 1999. This 10-track collection represents Cameo's funkier side, and can be viewed as a companion piece to the previous year's The Ballads Collection. The album contains two versions of "She's Strange" and a previously unreleased mix of "Back and Forth".


12" Masters – Essential Mixes
12" Masters – Essential Mixes (commonly referred to as simply Essential Mixes) is a remix album by Australian pop singer Kylie Minogue. It was released on 17 September 2010, by Sony Music Entertainment. The album contains remixes of tracks from her 1994 and 1998 studio albums: Kylie Minogue and Impossible Princess.


12" Masters – Essential Mixes
Remixers who contribute to the album include Felix da Housecat, Trouser Enthusiasts, Quivver, Sash!, Justin Warfield, and TNT. Brothers in Rhythm, who produced her album Impossible Princess, also remixed the track "Too Far".


12" Masters – The Essential Mixes
12" Masters – The Essential Mixes (commonly referred to as simply Essential Mixes) is a remix album by American singer and songwriter Justin Timberlake. It was released on September 17, 2010, by Sony Music Entertainment and Jive Records. The album contains remixes of tracks from his first two studio albums: Justified (2002) and FutureSex/LoveSounds (2006).


12" Masters – The Essential Mixes, Composition
12" Masters – The Essential Mixes features 11 "club-friendly reworkings" of Timberlake's singles spanning from 2002 to 2007.


12" Masters – The Essential Mixes, Critical reception
According to Jon O'Brien of AllMusic, 12" Masters – The Essential Mixes will "at the very least bump up his sparse back catalog", suggesting that it will satisfy his "army of fans" that are desperate for new music. He noted that remix albums are "notoriously hard to pull off", as they have the tendency to "smother the original" in "generic pounding beats" and "repetitive synths", which leads to the concept's downfall.


12" Masters – The Essential Mixes, Critical reception
O'Brien wrote that: "Luckily, Essential Mixes, one of a series of a 2010 releases that has also tackled the works of Kylie Minogue, Usher, and Avril Lavigne, features a consistently stellar lineup of hotshot and well-respected producers who are a cut above the copy-and-paste merchants usually wheeled out for these types of affairs." He concluded that, while the album "doesn't always do justice to the consistently brilliant source material", it is an "intriguing stopgap" that shows Timberlake's sound is "capable of translating to the Ibiza dance scene as well as the U.S. R&B clubs".


12"/50 caliber gun (Argentina)
The 12"/50 caliber Bethlehem gun was a US naval gun designed in 1910 as the main armament for the Argentine Navy’s dreadnought battleships of the  Rivadavia class.


12"/50 caliber gun (Argentina), Design
The gun was designed in 1910, and it was probably based on the US 12"/50 (30.5 cm) Mark 7 naval gun with a breech weight added. The guns were manufactured at the Bethlehem Steel Corporation. The ships in the class had twelve 305 mm guns each, mounted in six twin (2-gun) turrets, with two turrets forward, two aft, and one on each side.


12"/50 caliber gun (Argentina), Measurements and Capabilities
The gun weighed 66 tons including the breech and was capable of an average rate of fire of 2–3 rounds a minute. It could throw an 870 lb. (394.6 kg) Mark 15 armor-piercing shell 24,000 yards (21,950 meters) at an elevation of 14.7°, while the "barrel life" of the guns was 200 shots.


12"/50 caliber gun (Argentina), Measurements and Capabilities
The previous 12" gun, manufactured for the U.S. Navy, was the Mark 7 version, a very similar gun which had been designed and installed in the 1912 era  Wyoming-class battleships.


12"/50 caliber gun (Argentina), Service
This gun was only installed in the Argentine Navy Rivadavia-class battleships Rivadavia and Moreno.


12"ers
12"ers (pronounced 12 Inchers) is a remix album by the English singer-songwriter Phil Collins, the lead vocalist and drummer for the rock band Genesis. The album contains six tracks from his 1985 hit album, No Jacket Required, remixed. All special extended remixes are by John 'Tokes' Potoker, except for "One More Night" remixed by Hugh Padgham. The remixes on this album were originally released on various 12-inch LP singles which were taken from the album No Jacket Required, hence the name.


12"ers
In Japan and Brazil, the release was originally a four-track EP, released on 12" and cassette. The main difference is the omission of remixes for "Who Said I Would" and "Only You Know and I Know" and the inclusion of an edited remix for "Take Me Home" which clocked in at 6:10. When the album was released on CD in 1988, it was the full six-track album, including the full length remix of "Take Me Home".


12"ers, Original releases
"Don't Lose My Number", "Take Me Home", "Sussudio" and "One More Night" were all released as 12" singles A-sides. "Only You Know and I Know" was released as the B-side of the "Separate Lives" 12" single. "Who Said I Would" is exclusive to the CD edition of this compilation.


12"ers, Critical reception
Reviewing retrospectively for AllMusic, critic Shawn M. Haney wrote of the album "The album is a great way to reflect back on one's wondrous memories of '80s life. This will find the listener in the middle of an enjoyable musical experience, especially for those who were and continue to be a part of Collins' fan base."


12"ers, Track listing
All tracks are written by Phil Collins, except where noted.


12"x12 New Order Vinyl Campaign
12" x 12 New Order Vinyl Campaign is the title of a series of 12-inch singles released by New Order in February 2006 through New State Recordings. The discs contain a mixture of both new and previously released remixes of past New Order songs. NSER017, which contains mixes of "Blue Monday", charted in the UK top 75.


12, Smart
12, Smart (12,スマート, 12, Smart) is the twelfth studio album by all-girl Japanese idol group Morning Musume.


12, Smart, Overview
It is the last album to feature Ai Takahashi, Risa Niigaki, and Aika Mitsui and the first to feature the ninth-generation members Mizuki Fukumura, Erina Ikuta, Riho Sayashi, and Kanon Suzuki.


12-12-12
12-12-12 is a documentary film that premiered on October 29, 2013 at the Directors Guild of America theater on Sunset Boulevard in Hollywood.


12-12-12
Filmed from 23 different camera angles, the documentary was originally to have been two separate films, made by two separate production groups, one headed by Sir Paul McCartney, and one from the Robin Hood Foundation's film team. After production crews encountered one another at Madison Square Garden during filming, the two teams joined forces to create a single film using both companies' equipment and resources.


12-12-12
On December 12, 2012, some of entertainment's most iconic names came together at Madison Square Garden for a historic concert to benefit the victims of Hurricane Sandy, 12-12-12: The Concert for Sandy Relief.


12-12-12
It was produced jointly by James Dolan, Executive Chairman of The Madison Square Garden Company; John Sykes, President of Entertainment Enterprises for Clear Channel Media Holdings. ; and Harvey Weinstein, Co-Founder and Chairman of The Weinstein Company, and presented by Chase with all proceeds going to the Robin Hood Relief Fund.


12-12-12
12-12-12 covers behind-the-scenes and onstage moments from the historic concert -- "the largest gathering of old British musicians ever in Madison Square Garden" an until-then unprecedented gathering of musicians, performers, and public figures who took the stage or worked behind the scenes to raise over fifty million U.S. dollars in one night for the Robin Hood Hurricane Sandy Relief Fund and to quickly distribute the entirety of the funds to organizations helping victims in New York, New Jersey and Connecticut.


12-12-12
Edited in a roughly sequential fashion, the film is at once: a documentary about community heroism; a concert film; and an exploration of the wide range of efforts needed to produce such a concert, from gathering the artists, to planning the event, through load-in and rehearsal, solving "money problems" and technical issues with web-based donations, and finally the performances themselves.


12-12-12: The Concert for Sandy Relief
12-12-12: The Concert for Sandy Relief was a benefit concert that took place at Madison Square Garden in New York City on December 12, 2012.


12-12-12: The Concert for Sandy Relief
The concert was held in response to Hurricane Sandy, which devastated portions of the Northeastern United States, the Caribbean and the Mid-Atlantic in late October 2012 and cost an estimated $60 billion in damage in the United States. The concert was broadcast live via television, radio, movie theaters and the Internet, and released on DVD and CD. A documentary film was also made about the concert. Proceeds from the event were collected by the Robin Hood Relief Fund to benefit victims of the hurricane in New York, New Jersey and Connecticut.


12-12-12: The Concert for Sandy Relief
Many famous performers took part in the charity event, including The Who, Bruce Springsteen, Alicia Keys, Bon Jovi, Eric Clapton, Billy Joel, The Rolling Stones, Roger Waters, Chris Martin, Michael Stipe, Kanye West, Eddie Vedder, and, for the first time in eighteen years, the surviving members of Nirvana (Dave Grohl, Krist Novoselic and touring member Pat Smear) who performed together in a collaboration with Paul McCartney during his show-closing set.


12-12-12: The Concert for Sandy Relief, Background
The benefit concert was first announced in mid-November 2012 and that the producers behind 2001's The Concert for New York City would also produce the Hurricane Sandy benefit which quickly attracted many big names from the music industry. The venue and on sale date for tickets were announced in early December. Madison Square Garden had originally been reserved on December 12 for a New York Rangers game against the Montreal Canadiens that was one of the 510 regular season games that were canceled due to the 2012–13 NHL lockout.


12-12-12: The Concert for Sandy Relief, Background
Proceeds from the event went to the Robin Hood Relief Fund and benefit victims of the hurricane in areas most impacted, especially New York, New Jersey and Connecticut. More than $30 million was raised through ticket sales alone.


12-12-12: The Concert for Sandy Relief, Tickets
Tickets for the event went on sale through Ticketmaster on December 3, 2012, at noon though Chase Bank customers were allowed to buy tickets at 9 a.m. Tickets quickly sold out in minutes. The face-value of tickets ranged from $150 to $2,500, with organizers saying all proceeds would go to the Robin Hood Foundation. Like most concerts with high demands for tickets, scalpers were able to buy tickets and within minutes of the concert selling out were already available for re-sale at much higher prices on various sites, including StubHub. By December 7, 2012, tickets for the floor in front of the stage were listed for as much as $48,000 while those in the upper level were going for $525 to $3,000.


12-12-12: The Concert for Sandy Relief, Tickets
Producers of the event urged people to not buy from these secondary websites because the money no longer goes to charity. U.S. Senator Charles E. Schumer sent a letter to StubHub and three other major online ticket exchanges, urging them to not allow sellers to profit from the demand for the concert stating that "Every dollar spent for these concert tickets should go to help the victims of Superstorm Sandy, not to line the pockets of unscrupulous scalpers". A spokesman for StubHub, Glenn Lehrman, said it did not have the technology to require sellers to give their profits to charity. StubHub gave its commissions of more than $500,000 to the charity.


12-12-12: The Concert for Sandy Relief, Tickets
Jacqueline Peterson, a spokeswoman for Ticketmaster, which handled the initial ticket sales, said her company had evidence that scalpers had used computer programs to snap up large numbers of tickets for resale. She said Ticketmaster had blocked thousands of sales to buyers that it identified as using these programs. Among the recipients of Schumer's letter were TicketMaster's in-house resale marketplaces, TicketsNow and TicketExchange; however, Peterson said that 12-12-12 tickets were not being allowed on those sites. TicketLiquidator, another secondary re-sale website, also said that it had declined to carry tickets for the concert.


12-12-12: The Concert for Sandy Relief, Broadcast
The concert was simulcast live on 39 U.S. television stations, including HBO, AMC, Showtime and AXS TV and on more than 20 international television networks. It was also streamed on over twenty-five websites, including Fuse.tv, MTV.com, AOL, Yahoo!, YouTube, SiriusXM, Hulu, and Vevo and over fifty radio stations. Select movie theaters in New York, New Jersey and Connecticut displayed the concert as well. Ion Television, Live Well Network and MundoFox were the only national over-the-air broadcasters to carry the concert. Locally, the PBS consortium WNET/WLIW/NJTV carried it on their stations, along with CBS's WLNY (Channel 55) and WRNN-TV (Channel 48). WPSG (Channel 57) carried the show locally in Philadelphia.


12-12-12: The Concert for Sandy Relief, Broadcast
Event producers James Dolan, John Sykes and Harvey Weinstein issued on December 3, 2012, the following joint statement: "The fact that so many major media companies are joining forces to distribute and stream this important event to homes worldwide will enable us to create a tremendous and unprecedented fundraising effort on a global scale to benefit the victims of this devastating storm."


12-12-12: The Concert for Sandy Relief, Broadcast
While every major U.S. media company aired the benefit on at least one of their networks, none of the major over-the-air television networks including CBS, ABC, Fox and NBC aired it, and neither did the major cable-news networks of CNN, MSNBC and the Fox News Channel. Clear Channel broadcast the concert live on some of its radio stations across the country and also streamed it live on iHeartRadio, its digital-radio service, and across the websites and Facebook pages of its 850 stations. The concert also aired in conjunction with the NBA's television and online streaming broadcasts in China and simulcast live on Clear Channel Outdoor digital billboards in Times Square and locations in London and Paris.


12-12-12: The Concert for Sandy Relief, Performers and segments
The event began at 7:30 pm and ran until 1:20 am.


12-12-12: The Concert for Sandy Relief (album)
The 12-12-12: The Concert for Sandy Relief is a compilation album by various rock and pop music artists, recorded live during the Hurricane Sandy relief concert 12-12-12: The Concert for Sandy Relief, held in New York's Madison Square Garden. The album was released on January 3, 2015 in the United States, and a European version was released on January 18 later the same year.


12-12-12: The Concert for Sandy Relief (album), Content
The album features best-of live performances by Eric Clapton, Adam Sandler, Paul Shaffer, Bon Jovi, Paul McCartney, Bruce Springsteen, Roger Waters, The Rolling Stones, Alicia Keys, Billy Joel, The Who and Chris Martin. The recording of these performances took place while the mentioned artists performed at 12-12-12: The Concert for Sandy Relief on December 31, 2012-January 1, 2013 in New York's Madison Square Garden. The album was released as a double compact disc with musical material of over nearly two and a half hours under Columbia Records.


12-12-12: The Concert for Sandy Relief (album), Content
Performers who are not included on the album release are: Billy Crystal, Susan Sarandon, Brian Williams, Ben Stiller, Whoopi Goldberg, Kristen Stewart, Tony Danza, Jon Stewart, Chelsea Clinton, Jimmy Fallon, Stephen Colbert, Sean Combs, Steve Buscemi, Chris Rock, Kanye West, Seth Meyers, Bobby Moynihan, Jack McBrayer, Jake Gyllenhaal, Blake Lively, Katie Holmes, Jason Sudeikis, Leonardo DiCaprio, Jamie Foxx, Quentin Tarantino, Christoph Waltz and Olivia Wilde.


12-12-12: The Concert for Sandy Relief (album), Chart performance
In Europe, the compilation album was not very successful peaking at position 83 on Switzerlands Schweizer Hitparade in February 2013. The 12-12-12: The Concert for Sandy Relief album reached number 60 in the Netherlands album chart, compiled by MegaCharts. On both of these album charts, the album stayed only one week, selling about 1,000 copies in each country. In Belgium, however, the all-star release placed itself on position 46 in Flanders and reached number 31 on the Ultratop Wallonia chart. In Flanders, the album stayed seven weeks on the chart, in Wallonia twelve weeks, making Belgium the most successful European territory in which the album reached the official national charts.


12-12-12: The Concert for Sandy Relief (album), Critical reception
For his AllMusic review, critic Stephen Thomas Erlewine notes the album is rare "star-studded" release, featuring "British classic rock royalty" with artists like "Roger Waters, the Who, The Rolling Stones and Eric Clapton". Erlewine, however, dislikes that "there is nothing from Kanye West and Dave Grohls collaboration with Paul McCartney" on the album. The critic mentions Eric Clapton's performance, stating "Clapton [is really] tearing into the Derek & the Dominos song 'Got to Get Better in a Little While'". Finishing his review for the music website, Erlewine awarded the release three out of five possible stars.


12-12-1950
12-12-1950 is a 2017 Indian Tamil language film written and directed by Selva, who starred as the lead role in the film. The movie is a tribute to the film actor Rajinikanth, and the title of the film corresponds to his birthday (December 12, 1950).


12-12-1950
The cast, apart from starring Selva, includes Ramesh Thilak, Adhavan, Ajai Prasad, Prashanth, Ashwini Chandrasekhar, Thambi Ramaiah, Yogi Babu, John Vijay, and M. S. Bhaskar. Selva has rechristened himself as Kabali Selva. The title teaser of the movie was released on 8 July 2017, and the film released on 8 December 2017.


12-12-1950, Plot
The film narrates the life of five fans of Rajinikanth.


12-12-1950, Release
The film's title 12-12-1950 meant that the film didn't have any problems with title changes during release. Other films that depicted Rajinikanth faced issues as those films explicitly stated Rajinikanth's name such as Main Hoon Rajinikanth and Perumaan The Rajinikanth.


12-3 incident
The 12-3 incident (Chinese: 一二·三事件; Portuguese: Motim 1-2-3) refers to political demonstrations and rioting against Portuguese rule in Macau that occurred on 3 December 1966. The incident, inspired by the Cultural Revolution in the People's Republic of China, occurred in direct response to a violent police crackdown against Chinese protestors demonstrating against corruption and colonialism in Macau. The incident is known as "12-3", in reference to the date of the riots. Pressured by business leaders in Macau and the mainland Chinese government, the colonial government agreed to meet the demands of the protestors and apologized for the police crackdown. Portuguese sovereignty over Macau diminished after the incident, leading to de facto Chinese control over the territory.


12-3 incident, Origins
The Portuguese occupation of Macau is broadly divided into three different political periods. The first, being the establishment of the first Portuguese settlement in Macau from 1557 until 1849. During this period the settlement administrators only had jurisdiction over the Portuguese community. The second period, known as the colonial period, scholars generally place from 1849 to 1974, it was in this period the Portuguese colonial administration began to take an active role in the lives of both the Portuguese and ethnic Chinese communities in Macau.


12-3 incident, Origins
On 26 March 1887, the Lisbon Protocol was signed, in which China recognized the "perpetual occupation and government of Macau" by Portugal who in turn, agreed never to surrender Macau to a third party without the consent of the Chinese government. This was reaffirmed in the Treaty of Peking on 1 December 1887. Throughout the colonial administration of Macau, development of Portuguese Macau stagnated due to a complex colonial bureaucracy and corruption. Racial segregation and division also existed throughout society. Within the governance of Macau, almost all government officers and civil service positions were held by local Portuguese residents.


12-3 incident, Origins
In September 1945, Republic of China Ministry of Foreign Affairs, expressed to the Portuguese government a desire to transfer Macau back to Chinese control. However, due to the Chinese Civil War, discussions related between the Kuomintang and the Portuguese were postponed indefinitely. In 1949, with the founding of the People's Republic of China a large number of refugees and Kuomintang supporters fled China to Portuguese Macau.


12-3 incident, Origins
Before the 12-3 incident, the Kuomintang and the Chinese Communist Party parties both maintained a presence in Macau. With the founding of the People's Republic, the colonial Portuguese government opened unofficial relations with China due to the close proximity of Macau to Communist controlled southern China. Following the founding of the PRC, the influence of the Chinese Communists grew substantially in Macau especially among business leaders throughout the region.


12-3 incident, The incident
Schools and education in Macau were divided on racial lines, with the Portuguese and Macanese sending their children to fully subsidized private schools while the Chinese population had to send their children to either Catholic or Communist schools. The segregation of education in Macau was an area of great contention for the local populations. In 1966, residents of Taipa Island, sponsored by the Chinese communists, tried to obtain permission to build a private school.


12-3 incident, The incident
Despite being granted a plot of land by the Portuguese authorities, Portuguese officials delayed the processing of the building permits, as they had not received any bribes from the residents of Taipa Island. In spite of receiving no building permits from the local administration, local residents began construction of the private school.


12-3 incident, The incident
On 15 November 1966, Urban Services Officers on Taipa blocked further construction of the school, leading to a confrontation between Chinese protesters and Macau Police. The police, including plain-clothes officers, injured over 40 people, of whom 14 were later detained.


12-3 incident, The incident
In response, a group of around 60 Chinese students and workers demonstrated outside the Governor's Palace in support of the residents of Taipa Island. The demonstrators shouted revolutionary slogans and read aloud from Mao Zedong's Little Red Book. On 3 December 1966, demonstrators began to riot and denounced Portuguese authorities for "fascist atrocities". Protestors, instigated by local communists and pro-Beijing business owners, ransacked Portuguese institutions throughout Macau such as the Macau City Hall and Public Notary's Office. Violence was also directed towards local Chinese businesses and organizations loyal to the Kuomintang. Unlike in neighboring Hong Kong - which faced similar leftist riots - the business community largely did not back the colonial government.


12-3 incident, The incident
In Mainland China, specifically in Guangdong, Red Guards, inspired by the Cultural Revolution and angered by the violence towards Chinese in Macau, began to protest in large numbers at the Chinese-Macau border.


12-3 incident, The incident
On 3 December, the colonial government ordered the rioters and demonstrators to be arrested, leading to even more mass discontent and popular support for opposition to the Portuguese administration. In response, demonstrators toppled the statue of Colonel Vicente Nicolau de Mesquita at Largo do Senado, the city center, and also tore off the right arm of a statue of Jorge Álvares located on the former outer harbor ferry port. At the Leal Senado or city hall, portraits of former governors were torn off the walls, and books and city records were tossed into the street and set on fire. Consequently, martial law was declared, authorizing a Portuguese military garrison and police to crack down on the protests. As a result, 8 people were killed by police and 212 were injured.


12-3 incident, Resolution
In response to the crackdown, the Portuguese government immediately implemented a news blockade, Portuguese-language newspapers and magazines were banned, and newspapers in Portugal and overseas provinces were ordered to censor reports about the incident. In response to the incident, the Chinese government deployed the People's Liberation Army to the Chinese-Portuguese Macau border to prevent Red Guards from invading Macau. Four Chinese warships also entered the waters of Macau in response to the crackdown. The security ring set around Macau by the Chinese would be involved in multiple casualty-causing conflicts with Red Guards attempting to invade Macau by both land and by sea.


12-3 incident, Resolution
The pro-Beijing community in Macau adopted a "Three No's" approach as a means to continue their struggle with the Government — no taxes, no service, no selling to the Portuguese. Representing Chinese Macau was the pro-Beijing Struggle Committee against Portuguese Persecution, known locally as the Committee of Thirteen. Chairman of the Committee was Leong Pui, the leader of the pro-Beijing Macau General Association of Labour.


12-3 incident, Resolution
Negotiations to resolve and prevent further escalation between the People's Republic of China, Committee of Thirteen, and the Portuguese government took place in Guangdong. The chief negotiator for the Chinese was Ho Yin, whose involvement and commitment to resolve the crisis caused by the riot was crucial because at that time he was the only one who could contact directly both the Portuguese administration and Chinese officials in Guangzhou and Beijing, as he was the representative of Macau in the Legislative Council.


12-3 incident, Resolution
The Portuguese, due to increasing pressures from both Beijing and Lisbon, agreed to sign agreements with the Committee of Thirteen and the Guangdong Government Foreign Affairs Bureau, along with an official statement of apology, and accepted responsibility for the events on 3 December 1966. On 29 January 1967, the Portuguese Governor, José Manuel de Sousa e Faro Nobre de Carvalho, with the endorsement of Portuguese Prime Minister Salazar, signed a statement of apology at the Chinese Chamber of Commerce, under a portrait of Mao Zedong, with Ho, as the Chamber's President, presiding.


12-3 incident, Resolution
Alongside the apology, the Portuguese agreed to reinforce the role of the Macau Chinese business elite in running the governmental affairs of Macau, promised to never use force against the Chinese community of Macau, and agreed to pay reparations to the Chinese community in Macau to the sum of 2 million Macanese pataca as compensation for the eight dead and 212 injured. In contrast, the agreement signed with the Guangdong government was more favorable to the Portuguese; per the agreement, the Chinese government would take back all refugees who arrived in Macau from 30 January 1967 on wards, a promise China would keep until 1978.


12-3 incident, Resolution
This marked the beginning of equal treatment and recognition of Chinese identity in Macau and the beginning of de facto Chinese control of the territory with Chinese Communist Ho Yin becoming the de facto governor of Macau. The Portuguese Foreign Minister, Alberto Franco Nogueira, described Portugal's role in Macau after 1967 as "a caretaker of a condominium under foreign supervision". Chinese media described the political situation of Macau as a "half liberated zone". Shortly after the agreements were signed, Chinese military forces around Macau were withdrawn and the Red Guard threat had subsided.


12-3 incident, Aftermath
With the Portuguese now only nominally in control of Macau, political power would increasingly rest with the pro-Beijing trade unions and business leaders. The official Portuguese and Chinese positions about the political status of Macau did not differ, as both now described the region as a Chinese territory under Portuguese administration and not a colony or overseas territory.


12-3 incident, Aftermath
As a consequence of Beijing's increasing influence, pro-Kuomintang activities in Macau were banned, and the Republic of China's diplomatic mission was closed. The flying of the flag of the Republic of China was banned, and Kuomintang-run schools were also closed. In addition, refugees from mainland China were either barred from entering or returned to China.


12-3 incident, Aftermath
Emboldened by their success against the Portuguese, the Committee of Thirteen encouraged demonstrations against other institutions in Macau that were perceived to be antagonistic towards the People's Republic. Specifically, the British Consulate and the Macau Branch of the Hong Kong Immigration department were once again targeted by protestors. British consular staff in Macau were under constant threat and harassment by Red Guards, leading to the closure of the British consulate in 1967.


12-3 incident, Aftermath
On 25 April 1974, a group of left-wing Portuguese officers organized a coup d'état in Portugal, overthrowing the right-wing ruling government that had been in power for 48 years. The new government began to transition Portugal to a democratic system and was committed to decolonization. The new Portuguese government carried out de-colonization policies and proposed Macau's handover to China to occur in 1978. The Chinese government rejected this proposal, believing that an early transfer of Macau would impact relations with Hong Kong.


12-3 incident, Aftermath
On 31 December 1975, the Portuguese government withdrew its remaining troops from Macau. On 8 February 1979, the Portuguese government decided to break off diplomatic relations with the Republic of China, and established diplomatic relations with the People's Republic of China the next day. Both Portugal and the People's Republic of China recognized Macau as Chinese territory. The colony remained under Portuguese rule until 20 December 1999, when it was transferred to China. Ho Yin's son, Edmund Ho Hau Wah, would become the first Chief Executive of the Macau Special Administrative Region following the transfer of sovereignty in 1999.


12-Bar Original
"12-Bar Original" is an instrumental 12-bar blues by the Beatles. It was recorded in 1965, but was not commercially available until 1996 when an edited version of take 2 of the song was included on the Anthology 2 album. Prior to editing, the length of take 2 was 6:36.


12-Bar Original
It is one of the few songs credited to Lennon/McCartney/Harrison/Starkey and published by Lenono Music, Inc., MPL Communications Ltd, Harrisongs Ltd., and Startling Music Ltd. Other songs credited to all four Beatles include "Flying" from Magical Mystery Tour, "Dig It" from Let It Be and "Christmas Time (Is Here Again)", the B-side to the 1995 single "Free as a Bird".


12-Bar Original
Of the Beatles, only John Lennon and Ringo Starr ever commented on the song. During some US radio interviews, Lennon was asked if there were any unissued Beatles recordings, he replied that all he could recall was "some lousy 12 bar". Starr told journalist Peter Palmiere that "we all wrote the track and I have an acetate of one of the versions". The quote was later used by Palmiere in a Ringo Starr cover interview/story in DISCoveries magazine in 1993 and by Jim Berkenstadt and Belmo in their book Black Market Beatles.


12-Bar Original
"12-Bar Original" was the Beatles' first instrumental after signing for EMI, and was produced by George Martin at EMI's Abbey Road Studios, London. Four other instrumentals by the group are the aforementioned "Flying", an outtake version of that song called "Aerial Tour Instrumental", "Cayenne" and "Cry for a Shadow".


12-Bar Original, Composition and recording
"12-Bar Original" was recorded on 4 November 1965, the same day as "What Goes On". Beginning with a count-in by McCartney, the track consists of 17 twelve-bar choruses in the key of E major, recorded without overdubs, with drums, bass, guitar and harmonium, clocking in at 6:42. For the track's release on Anthology 2, Martin edited together certain choruses: #1–2 (0:00–0:46), #9–10 (3:04–3:50),#14 (4:59–5:22) and #16–17 (5:46–6:38). The track was the first instrumental the group recorded since "Cry for a Shadow".


12-Crown-4
12-Crown-4, also called 1,4,7,10-tetraoxacyclododecane and lithium ionophore V, is a crown ether with the formula C8H16O4. It is a cyclic tetramer of ethylene oxide which is specific for the lithium cation.


12-Crown-4, Synthesis
12-Crown-4 can be synthesized using a modified Williamson ether synthesis, using LiClO4 as a templating cation:


12-Crown-4, Synthesis
It also forms from the cyclic oligomerization of ethylene oxide in the presence of gaseous boron trifluoride.


12-Crown-4, Properties
Like other crown ethers, 12-crown-4 complexes with alkali metal cations. The cavity diameter of 1.2-1.5 Å gives it a high selectivity towards the lithium cation (ionic diameter 1.36 Å)


12-Crown-4, Properties
Its point group is S4. The dipole moment of 12-crown-4 varies with solvent and temperature. At 25 °C, the dipole moment of 12-crown-4 was determined as 2.33 ± 0.03 D in cyclohexane and 2.46 ± 0.01 D in benzene.


12-Hydroxyeicosatetraenoic acid
12-Hydroxyeicosatetraenoic acid (12-HETE) is a derivative of the 20 carbon polyunsaturated fatty acid, arachidonic acid, containing a hydroxyl residue at carbon 12 and a 5Z,8Z,10E,14Z Cis–trans isomerism configuration (Z=cis, E=trans) in its four double bonds. It was first found as a product of arachidonic acid metabolism made by human and bovine platelets through their 12S-lipoxygenase (i.e. ALOX12) enzyme(s).


12-Hydroxyeicosatetraenoic acid
However, the term 12-HETE is ambiguous in that it has been used to indicate not only the initially detected "S" stereoisomer, 12S-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12(S)-HETE or 12S-HETE), made by platelets, but also the later detected "R" stereoisomer, 12(R)-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (also termed 12(R)-HETE or 12R-HETE) made by other tissues through their 12R-lipoxygenase enzyme, ALOX12B. The two isomers, either directly or after being further metabolized, have been suggested to be involved in a variety of human physiological and pathological reactions.


12-Hydroxyeicosatetraenoic acid
Unlike hormones which are secreted by cells, travel in the circulation to alter the behavior of distant cells, and thereby act as Endocrine signalling agents, these arachidonic acid metabolites act locally as Autocrine signalling and/or Paracrine signaling agents to regulate the behavior of their cells of origin or of nearby cells, respectively. In these roles, they may amplify or dampen, expand or contract cellular and tissue responses to disturbances.


12-Hydroxyeicosatetraenoic acid, Production
In humans, Arachidonate 12-lipoxygenase (12-LO, 12-LOX, ALO12, or platelet type 12-lipoxygenase) is encoded by the ALOX12 gene and expressed primarily in platelets and skin. ALOX12 metabolizes arachidonic acid almost exclusively to 12(S)-hydroperoxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12(S)-HpETE or 12S-HpETE). Arachidonate 15-lipoxygenase-1 (15-LO-1, 15-LOX-1, ALOX15), which is expressed in far more tissues that ALOX12, metabolizes arachidonic acid primarily to 15(S)-HpETE along with other metabolites of the 15-Hydroxyicosatetraenoic acid family; during this metabolism, however, ALOX15 also forms 12(S)-HpETE as a minor product.


12-Hydroxyeicosatetraenoic acid, Production
Arachidonate 12-lipoxygenase, 12R type, also termed 12RLOX and encoded by the ALOX12B gene, is expressed primarily in skin and cornea; it metabolizes arachidonic acid to 12(R)-HpETE. Cytochrome P450 enzymes convert arachidonic acid to a variety of hydroperoxy, epoxy, and dihydroxy derivatives including racemic mixtures of 12(S)-HpETE and 12(R)-HpETE or 12(S)-HETE and 12(R)-HETE; the R stereoisomer predominates in these mixtures. The initial 12(S)-HpETE and 12(R)-HpETE products, regardless of their pathway of formation, are rapidly reduced to 12(S)-HETE  and 12(R)-HETE, respectively, by ubiquitous cellular peroxidases, including in particular Glutathione peroxidases or, alternatively, are further metabolized as described below.


12-Hydroxyeicosatetraenoic acid, Production
Sub-primate mammals, such as the mouse, rat, rabbit, cow, and pig, express platelet type 12-lipoxygenase but also a leukocyte type 12-lipoxygenase (also termed 12/15-lipoxygenase, 12/15-LOX or 12/15-LO) which is an ortholog of, and metabolically equivalent to, human 15-LO-1 in that it forms predominantly 15(S)-HpETE with 12(S)-HpETE as a minor product. Mice also express an epidermal type 15-lipoxygenase (e-12LO) which has 50.8% amino acid sequence identity to human 15-LOX-2 and 49.3% sequence identity to mouse Arachidonate 8-lipoxygenase. Mouse e-12LO metabolizes arachidonic acid predominantly to 12(S)-HETE and to a lesser extent 15(S)-HETE.


12-Hydroxyeicosatetraenoic acid, Production
Sub-human primates, although not extensively examined, appear to have 12-lipoxygenase expression patterns that resemble those of sub-primate mammals or humans depending on the closeness of there genetic relatedness to these species.


12-Hydroxyeicosatetraenoic acid, Further metabolism
In human (and mouse) skin epidermis, 12(R)-HpETE is metabolized by Epidermis-type lipoxygenase, i.e. eLOX3 (encoded by the ALOXE3 gene), to two products: a) a specific hepoxilin, 8R-hydroxy-11R,12R-epoxy-5Z,9E,14Z-eicosatetraenoic acid (i.e. 8R-hydroxy-11R,12R-epoxy-hepoxilin A3 or 8R-OH-11R,12R-epoxy-hepoxilin A3) and b) 12-oxo-5Z,8Z,10E,14Z-eicosatetraenoic acid (12-oxo-HETE, 12-oxoETE, 12-Keto-ETE, or 12-KETE); 8R-hydroxy-11R,12R-epoxy-hepoxilin A3 is further metabolized by soluble Epoxide hydrolase 2 (sEH) to 8R,11R,12R-trihydroxy-5Z,9E,14Z-eicosatetraenoic acid. 12(R)-HpETE also spontaneously decomposes to a mixture of hepoxilins and trihydroxy-eicosatetraenoic acids that possess R or S hydroxy and epoxy residues at various sites while 8R-hydroxy-11R,12R-epoxy-hepoxilin A3 spontaneously decomposes to 8R,11R,12R-trihydroxy-5Z,9E,14Z-eicosatetraenoic acid. These decompositions may occur during tissue isolation procedures. Recent studies indicate that the metabolism by ALOXE3 of the R stereoisomer of 12-HpETE made by ALOX12B and therefore possibly the S stereoisomer of 12-HpETE made by ALOX12 or ALOX15 is responsible for forming various hepoxilins in the epidermis of human and mouse skin and tongue and possibly other tissues.


12-Hydroxyeicosatetraenoic acid, Further metabolism
Human skin metabolizes 12(S)-HpETE in reactions strictly analogous to those of 12(R)-HpETE; it metabolized 12(S)-HpETE by eLOX3 to 8R-hydroxy-11S,12S-epoxy-5Z,9E,14Z-eicosatetraenoic acid and 12-oxo-ETE, with the former product then being metabolized by sEH to 8R,11S,12S-trihydroxy-5Z,9E,14Z-eicosatetraenoic acid. 12(S)-HpETE also spontaneously decomposes to a mixture of hepoxilins and trihydroxy-eicosatetraenoic acids (trioxillins) that possess R or S hydroxy and R,S or S,R epoxide residues at various sites while 8R-hydroxy-11S,12S-epoxy-hepoxilin A3 spontaneously decomposes to 8R,11S,12S-trihydroxy-5Z,9E,14Z-eicosatetraenoic acid.


12-Hydroxyeicosatetraenoic acid, Further metabolism
In other tissues and animal species, numerous hepoxilins form but the hepoxilin synthase activity responsible for their formation is variable. (Hepoxilin A3 [8R/S-hydroxy-11,12-epoxy-5Z,9E,14Z-eicosatrienoic acid] and hepoxilin B3 [10R/S-hydroxy-11,12-epxoy-5Z,8Z,14Z-eicosatrienoic acid] refer to a mixture of Diastereomers and⁄or Enantiomers derived from arachidonic acid.) Cultured RINm5F rat Insulinoma cells convert 12(S)-HpETE to hepoxilin A3 in a reaction that is completely dependent on, and co-localizes with, the cells' leukocyte type 12-LOX; furthermore, recombinant rat and porcine leukocyte type 12-LOX as well as human platelet type 12-LOX metabolize 12(S)-HpETE to hepoxylin A3.


12-Hydroxyeicosatetraenoic acid, Further metabolism
However, transfection of HEK293 human embryonic kidney cells with each of the 6 rat lipoxygenases, including rat eLOX3, found that hepoxilin B3 production required eLOX3; furthermore, the development of inflammation-induced tactile pain hypersensitivity (hyperesthesia; tactile Allodynia) in rats required eLOX3-dependent production of hepoxilin B3 by spinal tissue. Thus, the production of hepoxilins from 12(S)-HpETE may result from the intrinsic activity of platelet or leukocyte type 12-LOX's, require eLOX3, or even result from 12(S)-HpETE spontaneous (and perhaps artefactual) decomposition during isolation. The majority of reports on hepoxilin formation have not defined the pathways evolved.


12-Hydroxyeicosatetraenoic acid, Further metabolism
Human and other mammalian cytochrome P450 enzymes convert 12(S)-HpETE to 12-oxo-ETE.


12-Hydroxyeicosatetraenoic acid, Further metabolism
12-HETE (stereoisomer not determined), 12(S)-HETE, 12-oxo-ETE, hepoxilin B3, and trioxilin B3 are found in the sn-2 position of phospholipids isolated from normal human epidermis and human psoriatic scales. This indicates that the metabolites are acylated into the sn-2 position after being formed and/or directly produced by the metabolism of the arachidonic acid at the sn-2 position of these phospholipids. These acylation reactions may sequester and thereby inactivate or store the metabolites for release during cell stimulation.


12-Hydroxyeicosatetraenoic acid, Further metabolism
12(S)-HETE and 12(R)-HETE are converted to 12-oxo-ETE by microsomal NAD+-dependent 12-hydroxyeicosanoid dehydrogenase in porcine polymophonuclear leukocytes; a similar pathway may be active in rabbit corneal epithelium, cow corneal epithelium, and mouse keratinocytes although this pathway has not been described in human tissues.


12-Hydroxyeicosatetraenoic acid, Further metabolism
12-oxo-ETE is metabolised by cytosolic NADH-dependent 12-oxoeicosinoid Δ10-reductase to 12-oxo-5Z,8Z,14Z-eicosatrienoic acid (12-oxo-ETrE); 12-ketoreductase may then reduce this 12-oxo-ETrE to 12(R)-hydroxy-5Z,8Z,14Z-eicosatrienoic acid (12(R)-HETrE) and to a lesser extent 12(S)-hydroxy-5Z,8Z,14Z-eicosatrienoic acid (12(S)-HETrE).


12-Hydroxyeicosatetraenoic acid, Receptor targets and mechanisms of action
The G protein-coupled receptor, GPR31, cloned from PC3 human prostate cancer cell line is a high affinity (Kd=4.8 nM) receptor for 12(S)-HETE; GPR31 does not bind 12(R)-HETE and has relatively little affinity for 5(S)-HETE or 15(S)-HETE. GPR31 mRNA is expressed at low levels in several human cell lines including K562 cells (human myelogenous leukemia cell line), Jurkat cells, (T lymphocyte cell line), Hut78 cells (T cell lymphoma cell line), HEK 293 cells (primary embryonic kidney cell line), MCF7 cells (mammary adenocarcinoma cell line), and EJ cells (bladder carcinoma cell line).


12-Hydroxyeicosatetraenoic acid, Receptor targets and mechanisms of action
This mRNA appears to be more highly expressed in PC3 and DU145 prostate cancer cell lines as well as in human umbilical vein endothelial cells (HUVEC), human umbilical vein endothelial cells (HUVEC), human brain microvascular endothelial cells (HBMEC), and human pulmonary aortic endothelial cells (HPAC). In PC-3 prostate cancer cells, GPR31 receptor mediates the action of 12(S)-HETE in activating the Mitogen-activated protein kinase kinase/Extracellular signal-regulated kinases-1/2 pathway and NFκB pathway that lead to cell growth and other functions. Studies have not yet determined the role, if any, in GPR31 receptor in the action of 12(S)-HETE in other cell types.


12-Hydroxyeicosatetraenoic acid, Receptor targets and mechanisms of action
A G protein-coupled receptor for the 5(S),12(R)-dihydroxy metabolite of aracidonic acid, Leukotriene B4, vis., Leukotriene B4 receptor 2 (BLT2), but not its Leukotriene B4 receptor 1, mediates responses to 12(S)-HETE, 12(R)-HETE, and 12-oxo-ETE in many cell types.


12-Hydroxyeicosatetraenoic acid, Receptor targets and mechanisms of action
Based on the effects of LTB4 receptor antagonists, for example, leukotriene B4 receptor 2 mediates: the rise in cytosolic Ca2+ concentration (a key signal for cell activation) in human neutrophils and the rise in cytosolic Ca2+ concentration and chemotaxis in Chinese hamstery ovarian cells stimulated by 12(S)-HETE, 12(R)-HETE, and/or 12-oxo-ETE; the itch response to 12(S)-HETE and PMN inflammatory infiltration response to 12(R)-HETE triggered by the injection these metabolites into the skin of  mice and guinea pigs, respectively; and an in vitro angiogenic response by Human umbilical vein endothelial cells (HUVEC) and in vivo angiogenic response by mice to 12(S)-HETE.


12-Hydroxyeicosatetraenoic acid, Receptor targets and mechanisms of action
The BLT2 receptor, in contrast to the GPR31 receptor, appears to be expressed at a high level in a wide range of tissues including neutrophils, eosinophils, monocytes, spleen, liver, and ovary. However, 12-Hydroxyheptadecatrienoic acid (i.e. 12-(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid or 12-HHT), a product made when prostaglandin H2 is metabolized to Thromboxane A2 by Thromboxane synthase or spontaneously rearranges non-enzymatically (see 12-Hydroxyheptadecatrienoic acid) is the most potent BLT2 receptor agonist detected to date.


12-Hydroxyeicosatetraenoic acid, Receptor targets and mechanisms of action
To clarify the role of BLT2 versus GPC31 receptors in responses to 12(S)-HETE, and the role(s) of LTB4, 12(S)-HETE, versus 12-HHT in BLT2-mediated responses, it will be necessary to determine: a) if leukotriene B4 interacts with the GPR31 receptor; b) if BLT2 receptor antagonists interfere with the GPR31 receptor; and c) the relative concentrations and availability of LTB4, 12(S)-HETE, and 12-HHT in tissues exhibiting BLT2-dependent responses. Ultimately, both receptors and all three ligands may prove to be responsible for some tissue responses in vivo.


12-Hydroxyeicosatetraenoic acid, Receptor targets and mechanisms of action
12(S)-HETE and 12(R)-HETE bind to and act as Competitive antagonists of the Thromboxane receptor which mediates the actions of Thromboxane A2 and Prostaglandin H2. This antagonistic activity was responsible for the ability of 12(S)-HETE and 12(R)-HETE to relax mouse mesenteric arteries pre-constricted with a thromboxane A2 mimetic, U46619.


12-Hydroxyeicosatetraenoic acid, Receptor targets and mechanisms of action
12(S)-HETE binds with high affinity to a 50 kilodalton (Kda) subunit of a 650 kDa cytosolic and nuclear protein complex.


12-Hydroxyeicosatetraenoic acid, Activities and possible clinical significance, Inflammation and inflammatory diseases
12(S)-HpETE, 12(R)-HETE, racemic mixtures of these 12-HETEs, and/or 12-oxo-ETE stimulate: a) the directed migration (chemotaxis) of human, rat, and rabbit neutrophils as well as rabbit macrophages; b) human neutrophils to adhere to each other (i.e. aggregate) and in cooperation with Tumor necrosis factor alpha or Platelet-activating factor, to release their granule-bound enzymes; c) the binding of human vascular epithelial cells to human monocytes; d) DNA synthesis and mitogenesis in the immortalized human keratinocyte cell line HaCaT; and e) when injected in the skin of human volunteers, the extravasation and local accumulation of circulating blood neutrophils and mononuclear cells.


12-Hydroxyeicosatetraenoic acid, Activities and possible clinical significance, Inflammation and inflammatory diseases
These results suggest these metabolites contribute to the inflammation that occurs as sites where they are formed in abnormal amounts such as in human rheumatoid arthritis, Inflammatory bowel disease, Contact dermatitis, psoriasis, various forms of Ichthyosis including Congenital ichthyosiform erythroderma, and corneal inflammatory diseases. Since BLT2 appears to mediate the responses of leukocytes to 12(S)-HpETE, 12(S)-HETE, 12(R)-HETE, and 12-oxo-ETE but GPR31 is expressed by various other cells (e.g. vascular endothelium) involved in inflammation, the pro-inflammatory actions of 12-HETE in humans may involve both types of G protein-coupled receptors.


12-Hydroxyeicosatetraenoic acid, Activities and possible clinical significance, Itch perception
12(S)-HpETE and 12(S)-HETE induce itching responses when injected into the skin of mice; this has led to the suggestion that these metabolites contribute to the itching (i.e. clinical pruritus) which accompanies such conditions as atopic dermatitis, contact dermatitis, urticaria, chronic renal failure, and cholestasis. Since it mediates 12(S)-HETE-induced itching in the mouse model, BLT2 rather than GPR31 may mediate human itch in these reactions.


12-Hydroxyeicosatetraenoic acid, Activities and possible clinical significance, Cancer, Prostate cancer
12-HETE (stereoisomer not defined) is the dominant arachidonic acid metabolite in cultured PC3 human prostate cancer cells and its levels in human prostate cancer tissue exceed by >9-fold its levels in normal human prostate tissue.


12-Hydroxyeicosatetraenoic acid, Activities and possible clinical significance, Cancer, Prostate cancer
Furthermore, 12(S)-HETE a) increases the expression of Alpha-v beta-5 cell surface adhesion molecule and associated with this the survival of cultured PC3 cells; b) promotes the phosphorylation of retinoblastoma protein to inhibit its tumor suppressor function while promoting the proliferation of cultured PC3 cells; c) stimulates PC3 cells to activate the Mitogen-activated protein kinase kinase/extracellular signal-regulated kinases-1/2 pathway and the NFκB pathways that lead to cell proliferation; d) reverses the apoptosis-inducing (i.e. cell-killing) effect of pharmacologically inhibiting 12-LO in cultured DU145 human prostate cancer cells; e) promotes the induction of cyclooxygenase-1 and thereby the synthesis of this enzyme's growth-promoting arachidonic acid metabolite, PGE2, in cultured PC3 and LNCaP human prostate cancer cells; and f) induces cultured PC3 cells to express Vascular endothelial growth factor (VEGF), a protein that stimulates the formation of the microvasclature which assists in the metastasis of cancer.


12-Hydroxyeicosatetraenoic acid, Activities and possible clinical significance, Cancer, Prostate cancer
These results suggest that the 12(S)-HETE made by prostate cancer tissues serves to promote the growth and spread of this cancer. Since it mediates the action of 12(S)-HETE in stimulating cultured PC3 cells to activate the Mitogen-activated protein kinase kinase/Extracellular signal-regulated kinases-1/2 pathway and NFκB pathways, the GPR31 receptor may contribute to the pro-malignant activity of 12(S)-HETE.


12-Hydroxyeicosatetraenoic acid, Activities and possible clinical significance, Cancer, Prostate cancer
However, LNCaP and PC3 cells also express BLT2 receptors; in LNCaP cells, BLT2 receptors are positively linked (i.e. stimulate the expression of) to the growth- and metastasis-promoting androgen receptor; in PC3 cells, BLT2 receptors stimulate the NF-κB pathway to inhibit the apoptosis caused by cell detachment from surfaces (i.e. Anoikis; and, in BLT2-overexpressing PWR-1E non-malignant prostate cells, 12(S)-HETE diminish anoikis-induced apoptosis. Thus, the role of 12(S)-HETE in human prostate cancer, if any, may involve its activation of one or both of the GPR31 and BLT2 receptors.


12-Hydroxyeicosatetraenoic acid, Activities and possible clinical significance, Cancer, Other cancers
Preclinical laboratory studies analogous to those conducted on the pro-malignant effects of 12(S)-HETE and growth-inhibiting effects of blocking 12-HETE production in cultured prostate cancer cell lines, have implicated 12-HETE (stereoisomer sometimes undefined) in cancer cell lines from various other human tissues including those from the liver, intestinal epithelium, lung, breast, skin (Melanoma), ovary, pancrease, and possibly bladder. These studies implicate the interaction of 12-HETE with BLT2 receptors in intestinal epithelium cancer cells, and BLT2 receptors in breast, ovary, pancreas, and bladder cancer cells. While the studies on these tissues have not been as frequent or diverse as those on prostate cancer cell lines, they are suggested to indicate that 12-HETE contributes to the growth or spread of the corresponding cancer in humans.


12-Hydroxyeicosatetraenoic acid, Activities and possible clinical significance, Diabetes
12(S)-HETE, 12(S)-HpETE, and with far less potency 12(R)-HETE reduced insulin secretion and caused apoptosis in cultured human pancreatic insulin-secreting Beta cell lines and prepared Pancreatic islets. TNFα, IL-1β, and IFNγ also reduced insulin secretion in cultured human pancreatic INS-1 beta cells, apparently by inducing the expression of NOX1 (NADPH oxidase 1) and thereby to the production of cell-toxic Reactive oxygen species; these cytokine effects were completely dependent on 12-lipoxygenase and mimicked by 12(S)-HETE but not 12(R)-HETE. 12-lipoxygenase-knockout mice (i.e., mice genetically manipulated to remove the Alox12 [


12-Hydroxyeicosatetraenoic acid, Activities and possible clinical significance, Diabetes
i.e. 12-lipoxygenase gene, see lipoxygenase#mouse lipoxygenases) are resistant to a) streptozotocin-induced, b) high fat diet-induced, and c) autoimmune-induced diabetes. Further studies in animal models suggest that the 12S-HETE made by pancreatic beta cells (or possibly alpha cells or other cell types indigenous to or invading the pancreatic islands) orchestrate a local immune response that results in the injury and, when extreme, death of beta cells. These results suggest that the 12-lipoxygenase-12S-HETE pathway is one factor contributing to immunity-based type I diabetes as well as low insulin output type II diabetes.


12-Hydroxyeicosatetraenoic acid, Activities and possible clinical significance, Blood pressure
12(S)-HETE and 12(S)-HpETE stimulate the dilation of rat mesenteric arteries; 12(S)-HETE stimulates the dilation of coronary microvessels in pigs and the mesenteric arteries of mice, one or more of these three metabolites are implicated in the vasodilation of rat basilar artery, 12(R)-HETE and to a slightly lesser extent 12(S)-HETE constrict the renal artery of dogs and 12-HETE (stereoisomer undetermined) is implicated in the angiotensin II-induced arterial hypertension response of human placenta. The vasodilating effect on mouse mesenteric arteries appears due to 12S-HETE's ability to act as a Thromboxane receptor antagonist and thereby block the vasoconstricting actions of thromboxane A2. These results indicate that the cited metabolites have dilating or constricting effects that depend on the arterial vascular site and or species of animal examined; their role in human blood pressure regulation is unclear.


12-Hydroxyheptadecatrienoic acid
12-Hydroxyheptadecatrenoic acid (also termed 12-HHT, 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid, or 12(S)-HHTrE) is a 17 carbon metabolite of the 20 carbon polyunsaturated fatty acid, arachidonic acid. It was first detected and structurally defined by P. Wlodawer, Bengt I. Samuelsson, and M. Hamberg as a product of arachidonic acid metabolism made by microsomes (i.e. endoplasmic reticulum) isolated from sheep seminal vesicle glands and by intact human platelets. 12-HHT is less ambiguously termed 12-(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid to indicate the S stereoisomerism of its 12-hydroxyl residue and the Z, E, and E cis-trans isomerism of its three double bonds. The metabolite was for many years thought to be merely a biologically inactive byproduct of prostaglandin synthesis. More recent studies, however, have attached potentially important activity to it.


12-Hydroxyheptadecatrienoic acid, Production, Primary source
Cyclooxygenase-1 and cyclooxygenase-2 metabolize arachidonic acid to the 15-hydroperoxy, 20 carbon prostaglandin (PG) intermediate, PGG2, and then to the 15-hydroxy, 20 carbon intermediate, prostaglandin H2 (PGH2). Thromboxane synthase further metabolizes PGH2 to the 20 carbon product, Thromboxane A2, the 17 carbon product, 12-HHT, and the 3 carbon product Malonyldialdehyde.


12-Hydroxyheptadecatrienoic acid, Production, Primary source
Platelets express cycloxygenase and thromboxane synthase enzymes, producing PGG2, PGH2, and TXA2 in response to platelet aggregating agents such as thrombin; these metabolites act as autocrines by feeding back to promote further aggregation of their cells of origin and as paracrines by recruiting nearby platlets into the response as well as exerting effects on other nearby tissues such as contracting blood vessels. These effects combine to trigger blood clotting and limiting blood loss.


12-Hydroxyheptadecatrienoic acid, Production, Primary source
12-HHT is a particularly abundant product of these pro-clotting responses, accounting for about one third of the total amount of arachidonic acid metabolites formed by physiologically stimulated human platelets. Its abundant production during blood clotting, the presence of cyclooxygenases and to a lesser extent thromboxane synthase in a wide range of cell types and tissue, and its production by other pathways imply that 12-HHT has one or more important bioactivities relevant to clotting and, perhaps, other responses.


12-Hydroxyheptadecatrienoic acid, Production, Other sources
Various cytochrome P450 enzymes (e.g. CYP1A1, CYP1A2, CYP1B1, CYP2E1, CYP2S1, and CYP3A4) metabolize PGG2 and PGH2 to 12-HHT and MDA. While the latter studies were conducted using recombinant cytochrome enzymes or sub-fractions of disrupted cells, the human monocyte, a form of blood circulating leukocyte, increases its expression of CYP2S1 when forced to differentiate into a macrophage phenotype by interferon gamma or lipopolysaccharide (i.e. endotoxin); associated with these changes, the differentiated macrophage metabolized arachidonic acid to 12-HHT by a CYP2S1-dependent mechanism. Future studies, therefore may show that cytochromes are responsible for 12-HHT and MDA production in vivo.


12-Hydroxyheptadecatrienoic acid, Production, Other sources
PGH2, particularly in the presence of ferrous iron (FeII), ferric iron (FeIII), or hemin, rearranges non-enzymatically to a mixture of 12-HHT and 12-HHT's 8-cis isomer, i.e., 12-(S)-hydroxy-5Z,8Z,10E-heptadecatrienoic acid. This non-enzymatic pathway may explain findings that cells can make 12-HHT in excess of TXA2 and also in the absence of active cycloxygenase and/or thromboxane synthase enzymes.


12-Hydroxyheptadecatrienoic acid, Further metabolism
12-HHT is further metabolized by 15-hydroxyprostaglandin dehydrogenase (NAD+) in a wide variety of human and other vertebrate cells to its 12-oxo (also termed 12-keto) derivative, 12-oxo-5Z,8E,10E-heptadecatrienoic acid (12-oxo-HHT or 12-keto-HHT). Pig kidney tissue also converted 12-HHT to 12-keto-5Z,8E-heptadecadienoic acid (12-oxo-5Z,8E-heptadecadienoic acid) and 12-hydroxy-heptadecadienoic acid.


12-Hydroxyheptadecatrienoic acid, Further metabolism
Acidic conditions (pH~1.1-1.5) cause 12-HHT to rearrange in a time- and temperature-dependent process to its 5-cis isomer, 12-hydroxy-5E,8E,10E-heptadecatrienoic acid.


12-Hydroxyheptadecatrienoic acid, Activities and clinical significance, Early studies
Fourteen years after the first publication on its detection in 1973, 12-HHT was reported to stimulate fetal bovine aortic and human umbilical vein endothelial cells to metabolize arachidonic acid to Prostacyclin I2 (PGI2), a powerful inhibitor of platelet activation and stimulator of Vasodilation (see Prostacyclin synthase); it did not, however, alter arachidonic acid metabolism in human platelets. Shortly thereafter, 12-HHT was reported to inhibit the chemotaxis-blocking effect of a human monocyte-derived factor on human moncytes while the immediate metabolite of 12-HHT, 12-oxo-HT, was reported to stimulate the chemotasis of human neutrophils.


12-Hydroxyheptadecatrienoic acid, Activities and clinical significance, Early studies
and to inhibit platelet aggregation responses to various agents by stimulating platelets to raise their levels of Cyclic adenosine monophosphate (cAMP), an intracellular signal that serves broadly to inhibit platelet activation. These studies were largely overlooked; in 1998 and 2007 publications, for example, 12-HHT was regarded as either inactive or without significant biological activity. Nonetheless, this early work suggested that 12-HHT may serve as a contributor to monocyte- and neutrophil-based inflammatory responses and 12-oxo-HT may serve as a counterpoise to platelet aggregation responses elicited or promoted by TXA2.


12-Hydroxyheptadecatrienoic acid, Activities and clinical significance, Early studies
Relevant to the latter activity,  a later study showed that this inhibitory effect was due to the ability of 12-oxo-HT to act as a partial antagonist of the Thromboxane receptor: it blocks TXA2 binding to its receptor and thereby the responses of platelets and possibly other tissues to TXA2 as well as agents that depend on stimulating TXA2 production for their activity.


12-Hydroxyheptadecatrienoic acid, Activities and clinical significance, Early studies
Thus, 12-HHT forms simultaneously with, and by stimulating PGI2 production, inhibits TXA2-mediated platelet activation responses while 12-oxo-HT blocks TXA2 receptor binding to reduce not only TXA2-induced thrombosis and blood clotting but possibly also vasospasm and other actions of TXA2. In this view, thromboxane synthase leads to the production of a broadly active arachidonic acid metabolite, TXA2, plus two other arachidonic acid metabolites, 12-HHT and 12-oxo-HT, that serve indirectly to stimulate PGI2 production or directly as a receptor antagonist to moderate TXA2's action, respectively. This strategy may be essential for limiting the deleterious thrombotic and vasospastic activities of TXA2.


12-Hydroxyheptadecatrienoic acid, Activities and clinical significance, 12-HHT is a BLT2 receptor agonist
Leukotriene B4 (i.e. LTB4) is an arachidonic acid metabolite made by the 5-lipoxygenase enzyme pathway. It activates cells through both its high affinity (Dissociation constant [Kd] of 0.5-1.5 nM) Leukotriene B4 receptor 1 (BLT1 receptor) and its low affinity BLT2 receptor (Kd=23 nM); both receptors are G protein coupled receptors that, when ligand-bound, activate cells by releasing the Gq alpha subunit and pertussis toxin-sensitive Gi alpha subunit from Heterotrimeric G proteins.


12-Hydroxyheptadecatrienoic acid, Activities and clinical significance, 12-HHT is a BLT2 receptor agonist
BLT1 receptor has a high degree of ligand-binding specificity: among a series of hydroxylated eicosanoid metabolites of arachidonic acid, it binds only LTB4, 20-hydroxy-LTB4, and 12-epi-LTB4; among this same series, BLT2 receptor has far less specificity in that it binds not only LTB4, 20-hydroxy-LTB4, and 12-epi-LTB4 but also 12(R)-HETE and 12(S)-HETE (i.e. the two stereoisomers of 12-Hydroxyeicosatetraenoic acid) and 15(S)-HpETE and 15(S)-HETE (i.e. the two stereoisomers of 15-Hydroxyicosatetraenoic acid). The BLT2 receptor's relative affinities for finding LTB4, 12(S)-HETE, 12(S)-HpETE, 12(R)-HETE, 15(S)-HETE, and 20-hydroxy-LTB4 are ~100, 10, 10, 3, 3, and 1, respectively.


12-Hydroxyheptadecatrienoic acid, Activities and clinical significance, 12-HHT is a BLT2 receptor agonist
All of these binding affinities are considered to be low and therefore indicating that some unknown ligand(s) might bind BLT2 with high affinity. In 2009, 12-HHT was found to bind to the BLT2 receptor with ~10-fold higher affinity than LTB4; 12-HHT did not bind to the BLT1 receptor. Thus, the BLT1 receptor exhibits exquisite specificity, binding 5(S),12(R)-dihydroxy-6Z,8E,10E,14Z-eicosatetraenoic acid (i.e. LTB4) but not LTB4's 12(S) or 6Z isomers while the BLT2 receptor exhibits a promiscuous finding pattern. Formyl peptide receptor 2 is a relevant and well-studied example of promiscuous receptors.


12-Hydroxyheptadecatrienoic acid, Activities and clinical significance, 12-HHT is a BLT2 receptor agonist
Initially thought to be a second and low affinity receptor for the neutrophil tripeptide chemotactic factor, N-formyl-met-leu-phe, subsequent studies showed that it was a high affinity receptor for the arachidonic acid metabolite, lipoxin A4, but also bound and was activated by a wide range of peptides, proteins, and other agents. BLT2 may ultimately prove to have binding specificity for a  similarly broad range of agents.