20,000 Leagues Under the Sea: Submarine Voyage, Closure
Though the attraction was a guest favorite and remained popular throughout its existence, it was expensive to maintain, as well as having a low hourly loading capacity for an attraction of its size and expense. It was closed on September 5, 1994, without advance notice, for what was outwardly termed a temporary maintenance period. The ride was set to reopen in the summer of 1996, but in April of the same year, the closure was officially made permanent.


20,000 Leagues Under the Sea: Submarine Voyage, Closure
Post-closure, several vehicles were left stationary in the lagoon and by the dock, before the entire fleet was eventually pulled from the attraction in 1996. The submarines were regularly moved around to different locations in Walt Disney World backstage for several years, until eventually being stripped and buried in a landfill in 2004. Three of the vehicles were saved from the fleet's demise. Two were shipped to be sunk in the snorkeling lagoon at Castaway Cay, Disney's private island.


20,000 Leagues Under the Sea: Submarine Voyage, Closure
Here, the two submarines were placed in various areas of the snorkeling lagoon and covered with cargo netting to help sea life and microbial corrosion cling to them. As of 2008, only one of those two Nautilus submarines still exists, but both its wheelhouse and dorsal fin have been destroyed by hurricane weather. The third submarine was first moved to queue for the backlot tour at Disney's Hollywood Studios, but was eventually moved to an empty lot. When the tour was still open, it could be seen next to some props from Star Wars or Pirates of the Caribbean. When the tour closed, the submarine was put in storage, but it has been taken out and displayed at various Disney events, still in fairly good condition.


20,000 Leagues Under the Sea: Submarine Voyage, Closure
The lagoon remained as a scenic viewpoint (and was renamed "Ariel's Grotto", complete with a King Triton spouting statue) until 2004, when the water was drained and the sets and infrastructure were demolished. Pooh's Playful Spot was built where the attraction formerly stood and operated between 2005 and 2010 before making way for the Seven Dwarfs Mine Train as part of the Fantasyland Expansion.


20,000 Leagues Under the Sea: Submarine Voyage, Closure
However, the exterior to The Little Mermaid: Ariel's Undersea Adventure contains a silhouette of the Nautilus in a rock wall and the tiki bar Trader Sam's Grog Grotto at Disney's Polynesian Village Resort serves a cocktail called the "Nautilus" which is itself served in a stylized drinking vessel resembling the submarine.


20,000 Martyrs of Nicomedia
The 20,000 Martyrs of Nicomedia refers to victims of persecution of Christians in Nicomedia, Bithynia (modern Izmit, Turkey) by the Roman Emperors Diocletian and Maximian in the early 4th century AD.


20,000 Martyrs of Nicomedia
According to various martyrologies and menologion, the persecution included the burning of a church that held numerous Christians on Christmas Day.


20,000 Martyrs of Nicomedia
This event took place when the emperor Maximian (284-305) returned with victory over Ethiopians in 304 AD. It happened after they had refused to sacrifice to idols during Christmas Mass in order to thank gods for the victory he had acquired. Later Maximian and his soldiers entered the church and told the Christians they could escape punishment if they renounced Christ. The Christian priest Glycerius answered that the Christians would never "renounce their faith, even under the threat of torture". Maximian ordered him to be burned to death. Those who had not been burned in the church were captured and tortured to death. The bishop Anthimos who had escaped burning in the church was captured and beheaded.


20,000 Martyrs of Nicomedia
The number 20,000 may be apocryphal. However, the martyrs of Nicomedia continue to be honored with feast days: they are commemorated on 28 December in the Eastern Orthodox Church, and by the Byzantine Catholic Churches. In the Roman Martyrology of the Roman Catholic Church, there are separate entries for groups of martyrs of Nicomedia. The martyrdom of Anthimus of Nicomedia and companions is commemorated on 24 April and "the commemoration of many holy martyrs of Nicomedia" on June 23.


20,000 Men a Year
20,000 Men a Year (aka Air Story and Aviation Story) is a 1939 American action film directed by Alfred E. Green and written by Lou Breslow and Owen Francis. The film stars Randolph Scott, Preston Foster, Margaret Lindsay, Mary Healy, Robert Shaw, George Ernest, Jane Darwell, Kane Richmond and Maxie Rosenbloom. It was the fourth and last film produced by Cosmopolitan Pictures in its final year of operation.


20,000 Men a Year
Long before the attack on Pearl Harbor, the U.S. government had encouraged Hollywood to produce films designed to encourage a buildup of the aviation industry as well as the military. The release of 20,000 Men a Year on October 27, 1939 by 20th Century Fox reflected the spirit of the times.


20,000 Men a Year, Plot
Brad Reynolds is a respected pilot for Pacific Airlines. On a flight from Salt Lake City to Los Angeles, his aircraft hits a thick bank of fog. Reynolds and his co-pilot, Al Williams, are told by their dispatcher to re-route to Saugus, California, but Brad safely lands in Los Angeles anyway. Jim Howell, the Southwestern representative for the Civil Aeronautics Authority (CAA), and Brad's old nemesis, suspends Brad for 60 days who angrily quits. Brad buys the Comet Airport in Riverdale, California. The airport mechanic Walt Dorgan is its only asset.


20,000 Men a Year, Plot
Ann Rogers tells Brad that her brother Skip, Brad's top student, is flying without his family's consent. Brad is forced to return Skip's deposit just when the bank is about to foreclose on the airport. Brad tries to return to Pacific Airlines to ask for his old job, but is told that he is too old.


20,000 Men a Year, Plot
Meanwhile, the CAA begins a Civilian Pilot Training Program at selected universities, with local airports being used. Unknown to Brad, Jim Howell convinces Riverdale banker Crandall to back Brad's airport, as nearby Western Institute of Technology is chosen. Brad becomes an instructor and begins selecting and training his students. Transferring to Western from Texas State is Tommy Howell, Jim's little brother.


20,000 Men a Year, Plot
Skip, unable to get his sister's permission to fly, becomes Tommy's roommate, and arranges a meeting between Brad and Ann. Skip is allowed to take a ground crew course. During flight training, Tommy admits to Brad that he is afraid to fly and does so only to please his older brother. Brad gives Tommy early morning lessons in secret.


20,000 Men a Year, Plot
Jim thinks that Brad is unfair to his brother, but during one of Tommy's secret lessons, the aircraft's oil line breaks. Brad is forced to knock him out in order to release his hands on the throttle.


20,000 Men a Year, Plot
Tommy, thinking the aircraft is crashing, parachutes out over a cavernous mountain range. Brad lands the aircraft safely and convinces a farmer to drive him back to the airport. He takes a second aircraft up to search for Tommy, with Skip joining him.


20,000 Men a Year, Plot
Tommy is found hanging by his parachute from a tree over a cliff and when Brad climbs the tree to release Tommy, a branch breaks, throwing Brad to the ground. With both legs injured, Brad is now unable to fly. When the group does not return, Walt is forced to tell Dean Norris all.


20,000 Men a Year, Plot
Norris calls Jim and a search begins. The next morning, however, Skip tells Brad he must fly the aircraft out himself if the two are to survive. Brad agrees, giving Skip strict instructions on how to fly the aircraft out of the canyon. Skip takes off, but knocks off his left landing gear trying to clear a mountain top.


20,000 Men a Year, Plot
At Comet Airport, Jim and his boss, Gerald Grant, await word from the search parties. Seeing Skip try to land, Walt blocks the runway with his jeep until Jim can take another aircraft up to warn Skip and Brad about their damaged aircraft.


20,000 Men a Year, Plot
Learning of the problem, Brad instructs Skip how to execute a safe landing, even on only two wheels. On his second pass at the runway, Skip successfully lands the aircraft.


20,000 Men a Year, Plot
Later, Tommy, Skip and the others finish their pilot training, as Brad and Ann are now together, planning their own futures.


20,000 Men a Year, Production
Based on a story by veteran pilot and screenwriter, Frank "Spud" Wead, 20,000 Men a Year was the first film to document the Civilian Pilot Training Program. The sequences on both the ground and in the air, serve as a semi-documentary of the program.


20,000 Men a Year, Production
The film was shot at various locations including, in Zion National Park, the Grand Canyon, Cedar City, Utah and at Occidental College, Los Angeles, as well as the Monrovia Airport in Monrovia, California. Principal photography for 20,000 Men a Year took place on location from August 26 to October 1938.


20,000 Men a Year, Production
The aircraft used in 20,000 Men a Year were provided by stunt pilot Paul Mantz who acted as the "air boss" and coordinated aerial photography. The aircraft included his Stearman C3 as a camera platform.


20,000 Men a Year, Reception
Film reviewer for The New York Times, Frank Nugent, described 20,000 Men a Year as "Never more than a sleeper jump behind the times, the screen has hurried around to the Roxy with a melodramatic salute to the aviation training program instituted not so long ago by the Civil Aeronautics Authority. '20,000 Men a Year', which is a statistical reference to the number of civil pilots the CAA hopes to be turning out ..."


20,000 Streets Under the Sky
20,000 Streets Under the Sky is a trilogy of semi-autobiographical novels by Patrick Hamilton.


20,000 Streets Under the Sky
The three books are The Midnight Bell (1929), The Siege of Pleasure (1932) and The Plains of Cement (1934). They focus on three of the people who populate The Midnight Bell pub in London; the stories interconnect.


20,000 Streets Under the Sky
The first book in particular contains autobiographical elements—Hamilton worked in London pubs before becoming a successful writer, was infatuated with a prostitute at that time, and eventually died of liver failure caused by alcoholism. The books are also notable for their portrayal of working class London in the inter-war period.


20,000 Streets Under the Sky
The trilogy was published in paperback by Vintage in 2004 (ISBN 0-09-947916-8).


20,000 Streets Under the Sky, Plot summary
The Midnight Bell tells the story of Bob, a sailor turned bar waiter who becomes infatuated with Jenny, a prostitute who visits the pub. Ella, the barmaid at the pub, is secretly in love with Bob. In one of the most autobiographical narratives Hamilton ever wrote, Bob squanders his life savings on Jenny, whose lack of interest in Bob (beyond his money) is painfully evident to all but Bob. Eventually, Jenny loses all interest once Bob has spent all his savings on her.


20,000 Streets Under the Sky, Plot summary
The Siege of Pleasure is the shortest of the three stories, and recounts a little over twenty-four hours in Jenny's earlier life. She gets a new job as a housemaid to two elderly sisters, but later the same day along with her friend encounters three men in a bar. She elects to stand her erstwhile boyfriend up, gets drunk and is involved in a car accident where there is a possible fatality. The following morning, having spent the night in the home of one of the men, she determines not to go back to the sisters' employ. Bob and Ella do not feature at all in this novel.


20,000 Streets Under the Sky, Plot summary
The Plains of Cement is set during the events in The Midnight Bell, with Ella as the focus. Ella, still nursing a sublimated affection for Bob, has to deal with the increasingly unwelcome (and not always comprehensible) advances of the lower-middle class Ernest Eccles, an elderly customer of the pub. She is torn between a possible escape from her dull routine and a potential marriage to a man she does not love. We are also introduced to Ella's mother, trapped in a loveless marriage to Ella's violent stepfather. One of the episodes is a replication of that in The Midnight Bell, but told from Ella's perspective. The narrative concludes one day after the final scene of The Midnight Bell.


20,000 Streets Under the Sky, Plot summary
A common theme across all three stories is Hamilton's use of "narrated monologue or free indirect discourse", wherein a single character's thoughts (in this trilogy Bob, Jenny and Ella respectively) are reproduced directly through the third-person narrator. This is particularly evident in the third section, where Ella is attempting to interpret Eccles' semi-coherent intentions, from trying to work out if a bunch of flowers are for her, to an apparent proposal of marriage.


20,000 Streets Under the Sky, Adaptations
The 1963 film Bitter Harvest was based on the trilogy.


20,000 Streets Under the Sky, Adaptations
In the 1990s the novels were adapted for BBC Radio Four in three episodes.


20,000 Streets Under the Sky, Adaptations
In 2005, the books were serialised as Twenty Thousand Streets Under the Sky starring Sally Hawkins, Zoe Tapper and Bryan Dick. It was shown on BBC Four, accompanied by the documentary Words, Whisky and Women. The three-part drama was also released on DVD, HD DVD and Blu-ray.


20,000 Streets Under the Sky (album)
20,000 Streets Under the Sky is an album by the band Marah, released in 2004.


20,000 Watt R.S.L.
20,000 Watt R.S.L. is a compilation album by Australian rock band Midnight Oil released in October 1997 on their own label Sprint Music. The word "Collection" appears on the front of the CD along the hinge in the same type face as the title and the name of the band and may have been intended as part of the album's title; however, it does not appear on the spine. The release has also been distributed inside a cardboard sleeve which adds "Midnight Oil: The Hits" to the album art, distinguishing it as a compilation album.


20,000 Watt R.S.L.
The compilation covers the majority of Midnight Oil's career, starting with their 1979 album Head Injuries, and includes tracks from all their major studio releases (and one EP), even including two songs from the forthcoming Redneck Wonderland album, which was released after this compilation in 1998. The compilation does not include any material from the band's eponymous 1978 debut album or the Bird Noises EP (1980). The liner notes contain an essay on the band by Australian author Tim Winton.


20,000 Watt R.S.L.
The album peaked at #1 on the Australian Recording Industry Association (ARIA) album charts, and achieved 5×Platinum sales, it also peaked at #18 in New Zealand.


20,000 Watt R.S.L.
In 2012, Midnight Oil released the 2-disc compilation album Essential Oils, a more comprehensive summary of the band's career, and which includes material from all of the band's studio albums and EPs between 1978 and 2002. There is only one song ("What Goes On") included in 20,000 Watt R.S.L. that is not included in Essential Oils.


20,000 Watt R.S.L., Background
Midnight Oil is an Australian rock band from Sydney formed in 1976 with vocalist Peter Garrett, drummer Rob Hirst, bass guitarist Andrew James and keyboardist/lead guitarist Jim Moginie, Guitarist Martin Rotsey joined in 1977 and Midnight Oil established their own record label Powderworks, they released their second album Head Injuries on this label in October 1979. Founding bass guitarist James left due to illness in 1980, he was replaced by Peter Gifford, Gifford was himself replaced by Bones Hillman in 1987.


20,000 Watt R.S.L., Background
Australian Top Ten singles were "Power and the Passion", "The Dead Heart", "Beds Are Burning" and "Blue Sky Mine". Aside from chart success both "Power and the Passion" and "Beds Are Burning" were listed by Australasian Performing Right Association (APRA) in the Top 30 best Australian songs of all time in 2001. Through a long and distinguished career, the band became known for its driving hard-rock sound, intense live performances and political activism, particularly in aid of anti-nuclear, environmentalist and indigenous causes.


20,000 Years in Sing Sing
20,000 Years in Sing Sing is a 1932 American Pre-Code drama film set in Sing Sing Penitentiary, the maximum security prison in Ossining, New York, starring Spencer Tracy as an inmate and Bette Davis as his girlfriend. It was directed by Michael Curtiz and based upon the nonfiction book Twenty Thousand Years in Sing Sing, written by Lewis E. Lawes, the warden of Sing Sing from 1920 to 1941.


20,000 Years in Sing Sing
The film was remade by First National Pictures as Castle on the Hudson in 1940, starring John Garfield, Ann Sheridan, and Pat O'Brien.


20,000 Years in Sing Sing, Plot
Cocky Tommy Connors (Spencer Tracy) is sentenced from 5 to 30 years in Sing Sing for robbery and assault with a deadly weapon. His associate, Joe Finn (Louis Calhern), promises to use his contacts and influence to get him freed long before that, but his attempt to bribe the warden to provide special treatment is met with disdain and failure.


20,000 Years in Sing Sing, Plot
Connors makes trouble immediately, but several months confined to his cell changes his attitude somewhat. As the warden had predicted, Connors is only too glad to do some honest work on the rockpile after his enforced inactivity.


20,000 Years in Sing Sing, Plot
Nonetheless, his determination to break out is unshaken. Bud Saunders (Lyle Talbot), a highly educated fellow prisoner desperate to be with his pregnant wife, recruits him and Hype (Warren Hymer) for a complicated escape attempt. By chance, however, it is scheduled for a Saturday, which Connors superstitiously regards as always unlucky for him. He backs out, forcing Saunders to take another volunteer. The warden is tipped off and, though two guards are killed, the escape is foiled. Trapped, Saunders jumps to his death. His two accomplices are captured and returned to their cells.


20,000 Years in Sing Sing, Plot
Meanwhile, Connors' girlfriend, Fay Wilson (Bette Davis), visits him regularly in prison since his trial. On one visit, she admits she has become friendly and close to Finn in order to encourage him to help Connors, but Connors tells her that she is only giving Finn a reason to keep him locked up in jail.


20,000 Years in Sing Sing, Plot
The warden shows Connors a telegram that says that Wilson was injured in a car accident; there is no hope for her. Then, he gives Connors a 24-hour leave to see her; Connors promises to return, no matter what. When he sees Wilson, he learns that Finn was responsible for her injuries. He takes out a gun from a drawer, but Wilson persuades him to give her the pistol. Finn shows up, however, expecting her to sign a statement exonerating him in exchange for $5000 she intended to give to Connors. Connors attacks him. When it seems that Finn is about to kill her boyfriend, Wilson shoots him. Connors flees, taking the gun with him; Wilson secretly slips the money into his pocket. Before he dies, Finn names Connors as his killer.


20,000 Years in Sing Sing, Plot
The warden is lambasted in the newspapers for letting Connors go. Just when he is about to sign a letter of resignation, Connors walks in. He is found guilty of first-degree murder and sentenced to death in the electric chair, despite a recovered Wilson's testimony that she killed Finn. Connors comforts her before being taken to death row.


20,000 Years in Sing Sing, Production, Development
Bette Davis enjoyed working with Spencer Tracy, and had actually idolized him. The two wanted to do another movie together but never had the opportunity to do so, although they did appear together again on a radio version of Dark Victory in 1940.


20,000 Years in Sing Sing, Production, Development
Tracy, then under contract to Fox, was lent out to Warner Brothers for the film. It was originally intended for James Cagney, but at the time Cagney was having one of  his many misunderstandings with Jack L. Warner.


20,000 Years in Sing Sing, Box office
According to Warner Bros records the film earned $504,000 domestically and $431,000 foreign.


20,000 Years of Fashion
20,000 Years of Fashion: The History of Costume and Personal Adornment is a dictionary of western fashion from ancient times up to the 1960s, edited by Francois Boucher and his longtime assistant Yvonne Deslandres.


20,000 Years of Fashion
The book is widely cited as a reference for fashion trends in paintings and has 1150 illustrations which are mostly paintings, etchings and engravings from Western museums and collections. The book includes a glossary of terms and a bibliography of sources. It was originally published in French in 1965 as Histoire du Costume en Occident de l’antiquité à nos jours and was translated into English the next year, but was published after Boucher's death. In 1987 Deslandres updated a new edition with a section on modern fashion.


20,000 metres
The 20,000 metres (approximately 12.43 mi or 65,617 ft) is a rarely contested long-distance running event in track and field competitions; most world records in the event have been set during half marathons and one-hour races, as a half marathon is roughly 21,000 meters.


20,000 metres, World Records
+ = indicates a time was taken at an intermediate distance in a longer race


20,000 metres, All-time top 25, Women, Notes
Below is a list of other times equal or superior to 1:42:04.0:


20,000 metres, In popular culture
Tegla Loroupe's 20,000 meter world record was mentioned in Chapter 1, problem 64P of Chemistry (Seventh Edition) by John E. McMurry, Robert C. Fay, and Jill Kirsten Robinson.


20,000 metres race walk
The 20,000 metres race walk is a racewalking event. The event is competed as a track race. Athletes must always keep in contact with the ground and the supporting leg must remain straight until the raised leg passes it. 20,000 metres is 12.4274 miles.


20,000 metres race walk, History
This distance is not commonly raced at high level international competitions but part of South American Championships in Athletics and individual national championships (f.e. Russia, India, Colombia, Venezuela). Top level senior athletics racewalking events typically feature 20 km road distance.


20,000 metres race walk, World records
On May 7, 1994, Bernardo Segura of Mexico set a new 20,000 m race walk world record in Fana in a time of 1:17:25.6. The all-time women's 20,000 m race-walk record is held by Olimpiada Ivanova of Russia, at 1:26:53.2.


20,000 metres race walk, All-time top 25 (outdoor), Men, Notes
Below is a list of other times equal or superior to 1:20:40.3:


20,000 metres race walk, All-time top 25 (outdoor), Women, Notes
Below is a list of other times equal or superior to 1:32:21.59:


20,000 rials note
The twenty thousand rial banknote is a denomination of Iranian currency that was issued in 2003, and was considered its largest denomination until 2007.


20,000 rials note, Design
The note had been redesigned thrice in 2005, 2009 and 2014. The front displays a portrait of Rouhollah Khomeini. The original portrait was large, and never seen on any other banknote. In 2005, it was replaced by a smaller, more refined version. The 2004 version back side that featured Naqsh-e Jahan Square, had been redesigned twice. The version published in 2009 showed the al-Aqsa Mosque, which was replaced by Aghazadeh Mansion in the 2014 series. According to Christian Funke, both changes carried political motivations.


20-30 Bromfield Street
20-30 Bromfield Street is a historic commercial row in downtown Boston, Massachusetts. It is significant as being one of the few surviving 19th century commercial granite structures in the downtown area.


20-30 Bromfield Street, Description and history
The row was built during the height of Boston's so-called "Granite Era," which saw the proliferation of mercantile buildings made of granite, though few of these structures now remain. It consists of three sections separated by brick bearing walls, each 3.5 stories in height and three window bays wide. The second and third floors are faced in granite, while the roof is pitched and sheathed in slate. A series of two-story granite piers or pilasters are topped with Egyptoid capitals, a rare example of Egyptian revivalism in Boston.


20-30 Bromfield Street, Description and history
The row was built by John Ballard, a merchant whose family had long been active on Bromfield Street. Construction appears to have begun in 1847 and was complete by the following year. It originally consisted of five sections, but the two leftmost sections at 12-18 Bromfield were sold by Ballard's heirs and demolished in 1903 to make way for the Washington Building. The family had already relinquished ownership of 20-30 Bromfield by this time, being no longer in possession of the property by 1888.


20-30 Bromfield Street, Description and history
20-24 Bromfield Street was nearly gutted by a seven alarm fire on July 7, 1982, which caused over $500,000 in damages and destroyed several artists' studios, as well as the offices of the Gay Community News. Plans to tear down the structure in the aftermath of the fire were approved by the city building department, but were halted after the Boston Landmarks Commission issued an order prohibiting its demolition. The commission subsequently designated the 20-30 Bromfield Street exterior as a Boston Landmark on March 8, 1983.


20-Hydroxyecdysone
20-Hydroxyecdysone (ecdysterone or 20E) is a naturally occurring ecdysteroid hormone which controls the ecdysis (moulting) and metamorphosis of arthropods. It is therefore one of the most common moulting hormones in insects, crabs, etc. It is also a phytoecdysteroid produced by various plants, including Cyanotis vaga, Ajuga turkestanica and Rhaponticum carthamoides where its purpose is presumably to disrupt the development and reproduction of insect pests. In arthropods, 20-hydroxyecdysone acts through the ecdysone receptor. Although mammals lack this receptor, 20-hydroxyecdysone may affect mammalian (including human) biological systems in vitro, but there is uncertainty whether any in vivo or physiological effects occur. 20-Hydroxyecdysone is an ingredient of some supplements that aim to enhance physical performance. In humans, it is hypothesized to bind to the estrogen receptor beta (ERβ) protein-coding gene.


20-Hydroxyecdysone, Sources in arthropods
The primary sources of 20-hydroxyecdysone in larvae are the prothoracic gland, ring gland, gut, and fat bodies. These tissues convert dietary cholesterol into the mature forms of the hormone 20-hydroxyecdysone. For the most part these glandular tissues are lost in the adult with exception of the fat body, which is retained as a sheath of lipid tissue surrounding the brain and organs of the abdomen. In the adult female the ovary is a substantial source of 20-hydroxyecdysone production. Adult males are left with, so far as is currently known, one source of 20-hydroxyecdysone which is the fat body tissue. These hormone producing tissues express the ecdysone receptor throughout development, possibly indicating a functional feedback mechanism.


20-Hydroxyecdysone, Ecdysteroid activity in arthropods
An ecdysteroid is a type of steroid hormones in insects that are derived from enzymatic modification of cholesterol by p450 enzymes. This occurs by a mechanism similar to steroid synthesis in vertebrates. Ecdysone and 20-hydroxyecdysone regulate larval molts, onset of puparium formation, and metamorphosis. Being that these hormones are hydrophobic, they traverse lipid membranes and permeate the tissues of an organism. Indeed, the main receptor of these hormone signals - the ecdysone receptor - is an intracellular protein.


20-Hydroxyecdysone, In humans and other mammals, Use as supplement
20-Hydroxyecdysone and other ecdysteroids are marketed as ingredients in nutritional supplements for various sports, particularly bodybuilding. A comprehensive study, designed to find any strength or athletic improvement from 20-hydroxyecdysone, was published in 2006. The study looked for improvement in actual exercises performed and tested for improvements/increases in chemical indicators such as body composition and free/available testosterone. The results of the 2006 study concluded that using 30 mg per day of 20-hydroxyecdysone administered orally did not significantly affect anabolic or catabolic responses to resistance training, body composition, or training adaptations.


20-Hydroxyecdysone, In humans and other mammals, Use as supplement
However, a number of earlier studies (,) supported the anabolic effects of 20-Hydroxyecdysone. A more recent study conducted in 2019 by a team that included the Department for Molecular and Cellular Sports Medicine at the German Sport University Cologne, found that significantly higher increases in muscle mass were observed in participants dosed with ecdysterone, with significantly more pronounced increases in one-repetition bench press performance. The study was funded by the World Anti- Doping Agency (WADA) and demonstrated a significant dose-responsive anabolic effect of 20-Hydroxyecdysone supplementation on athletes during resistance training. Furthermore, recent studies () have elucidated that the mechanism of action of 20-Hydroxyecdysone on human muscle cells is relatively selective activation of the beta form of the estrogen receptor (ERβ), which is known to result in muscle hypertrophy.


20-Hydroxyecdysone, In humans and other mammals, Use as research tool
20-Hydroxyecdysone and other ecdysteroids are used in biochemistry research as inducers in transgenic animals, whereby a new gene is introduced into an animal so that its expression is under the control of an introduced ecdysone receptor. Adding or removing ecdysteroids from the animal's diet then gives a convenient way to turn the inserted gene on or off (see ecdysone receptor).


20-Hydroxyecdysone, In humans and other mammals, Use as research tool
At usual doses, 20-hydroxyecdysone appears to have little or no effect on animals that do not have extra genes inserted; it also has high bioavailability when taken orally, so it is useful for determining whether the transgene has been taken up effectively. For uses in gene therapy, it may be necessary to investigate more thoroughly the natural sources of ecdysteroids in humans (which appear to include dietary phytoecdysteroids, gut flora, helminth infections, and other diseases).


20-Hydroxyecdysone, In humans and other mammals, Use as research tool
There is some in vitro evidence to show that 20-hydroxyecdysone has effects on some kinds of blood cells such as lymphocytes and neutrophils, and may act as an immunomodulator as well as antioxidant on lipid peroxidation.


20-Hydroxyeicosatetraenoic acid
20-Hydroxyeicosatetraenoic acid, also known as 20-HETE or 20-hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoic acid, is an eicosanoid metabolite of arachidonic acid that has a wide range of effects on the vascular system including the regulation of vascular tone, blood flow to specific organs, sodium and fluid transport in the kidney, and vascular pathway remodeling. These vascular and kidney effects of 20-HETE have been shown to be responsible for regulating blood pressure and blood flow to specific organs in rodents; genetic and preclinical studies suggest that 20-HETE may similarly regulate blood pressure and contribute to the development of stroke and heart attacks. Additionally the loss of its production appears to be one cause of the human neurological disease, Hereditary spastic paraplegia. Preclinical studies also suggest that the overproduction of 20-HETE may contribute to the progression of certain human cancers, particularly those of the breast.


20-Hydroxyeicosatetraenoic acid, Biosynthesis, Production in humans
A subset of Cytochrome P450 (CYP450) microsome-bound ω-hydroxylases, the Cytochrome P450 omega hydroxylases, metabolize arachidonic acid to 20-HETE by an omega oxidation reaction. CYP450 enzymes belong to a superfamily which in humans is composed of at least 57 members and in mice at least 120 members. Among this superfamily, certain members of the CYP4A and CYP4F subfamilies in the CYP4 family are considered predominant cytochrome P450 enzymes that are responsible in most tissues for forming 20-HETE and, concurrently, smaller amounts of 19-hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoic acid (19-HETE). However, CYP2U1 may also contribute to the production of these two HETEs and CYP4F8 can metabolize arachidonic acid to 19-HETE while forming little or no 20-HETE.


20-Hydroxyeicosatetraenoic acid, Biosynthesis, Production in humans
The production of 19-HETE with 20-HETE may be significant since 19(R)-HETE, although not its stereoisomer, 19(S)-HETE, inhibits the action of 20-HETE on vascular endothelial cells. Based on studies analyzing the production of other HETEs by CYP enzymes, the production of 19-HETE by these enzymes may include both its R and S stereoisomers.


20-Hydroxyeicosatetraenoic acid, Biosynthesis, Production in humans
In humans, the CYP4 ω-hydroxylases include CYP4A11, CYP4F2, and CYP4F3 with the predominant 20-HETE-synthesizing enzymes being CYP4F2, which is the major 20-HETE producing enzyme in the human kidney, followed by CYP4A11. CYP4F3 is expressed as two distinct enzymes, CYP4F3A and CYP4F3B, due to alternative splicing of a single pre-mRNA precursor molecule; CYP4F3A is mostly expressed in leukocytes, CYP4F3B mostly in the liver.


20-Hydroxyeicosatetraenoic acid, Biosynthesis, Production in humans
Human CYP4Z1, which is expressed in a limited range of tissues such as human breast and ovary, may also metabolize arachidonic acid to 20-HETE while human CYP4A22, once considered as contributing to 20-HETE production, is now regarded as being metabolically inactive. Finally, CYP2U1, the only member of the human CYP2U subfamily, is highly expressed in brain and thymus and to lesser extents in numerous other tissues such as kidney, lung and heart. CYP2U1 protein is also highly expressed, compared to several other cytochrome P450 enzymes, in malignant breast tissue; the MCF-7 human breast cancer cell line express messenger RNA for this cytochrome.


20-Hydroxyeicosatetraenoic acid, Biosynthesis, Production by rodents and other animals
In mice, the only 20-HETE- and 19-HETE-producing enzymes of the Cyp4a subfamily are two extensively homologous ones, Cyp4a12a and Cyp4a12b; Cyp4a12a is expressed in the male kidney in an androgen hormone-dependent manner. In rats, Cyp4a1, Cyp4a2, Cyp4a3, and Cyp4a8 make 20-HETE. The tissue distribution of these enzymes differs from those of humans making extrapolations from rodent studies to humans somewhat complicated.


20-Hydroxyeicosatetraenoic acid, Biosynthesis, Production by rodents and other animals
Mouse CYP2J9, rat CYP2J3, and sheep CYP2J metabolize arachidonic acid primarily to 19-HETE but also to smaller amounts of 20-HETE, and, in the case of the sheep enzyme, 18-HETE; human CYP2J2, however, is an epoxygenase, metabolizing arachidonic acid to epoxide products.


20-Hydroxyeicosatetraenoic acid, Biosynthesis, Factors regulating 20-HETE production
Many agents stimulate cells and tissues to produce 20-HETE in vitro and in vivo. Androgens are particularly potent stimulators of this production. Other stimulators include the powerful vasoconstriction-inducing agents, angiotensin II, endothelins, and alpha adrenergic compounds (e.g. norepinephrine).


20-Hydroxyeicosatetraenoic acid, Biosynthesis, Factors regulating 20-HETE production
Nitric oxide, carbon monoxide, and superoxide inhibit 20-HETE production; these non-pharmacological agents do so by binding to the Heme binding site of the 20-HETE producing cytochrome p450 enzymes. Drugs that are substrates for the UDP-glucuronosyltransferase (UGT) enzymes which metabolize 20-HETE such as non-steroidal anti-inflammatory agents, opioids, gemfibrozil, Lasix, propanol, and various COX-2 inhibitors may act as perhaps unwanted side effects to increase the levels of 20-HETE. There are a variety of pharmacological agents which inhibit the synthesis of 20-HETE including various fatty acid analogs that compete reversibly with arachidonic acid for the substrate binding site in the CYP enzymes and benzene-based drugs.


20-Hydroxyeicosatetraenoic acid, Biosynthesis, Proviso on 20-HETE production
The cytochrome ω-oxidases including those belonging to the CYP4A and CYP4F sub-families and CYPU21 hydroxylate not only arachidonic acid but also various shorter chain (e.g. lauric acid) and/or longer chain (e.g. docosahexaenoic acid) fatty acids. They can also ω-hydroxylate and thereby reduce the activity of various fatty acid metabolites (e.g. LTB4, 5-HETE, 5-oxo-eicosatetraenoic acid, 12-HETE, and several prostaglandins) that regulate inflammation, vascular responses, and other reactions.


20-Hydroxyeicosatetraenoic acid, Biosynthesis, Proviso on 20-HETE production
This metabolism-induced inactivation may underlie the proposed roles of the cytochromes in dampening inflammatory responses and the reported associations of certain CYP4F2 and CYP4F3 single nucleotide variants with human Krohn's disease and Coeliac disease, respectively. While many of the effects and diseases associated with the over- or under-expression, pharmacological inhibition, and single nucleotide or mutant variants of the cytochrome ω-hydroxylases have been attributed to their impact on 20-HETE production, the influence of these alternate metabolic actions have frequently not been defined.


20-Hydroxyeicosatetraenoic acid, Metabolism
Glucuronidation of 20-HETE by UDP-glucuronosyltransferases (UGTs) is thought to be a primary pathway of 20-HETE elimination and thereby inactivation in humans.


20-Hydroxyeicosatetraenoic acid, Metabolism
There are several other pathways that metabolize 20-HETE. Human platelets and other tissues metabolize it via cyclooxygenase(s) to form the 20-hydroxy analogs of prostaglandin G2, thromboxane A2, thromboxane B2 and to 11(R)-hydroperoxy-20-hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoic acid which is rapidly reduced to 11,20-dihydroxy-5Z,8Z,11Z,14Z-eicosatetraenoic acid; they also metabolize it through 12-lipoxygenase to form 12(S)-hydroperoxy-20-hydroxy-5Z,8Z,101E,14Z-eicosatetraenoic acid which is also rapidly reduced to 12,20-dihydroxy-5Z,8Z,101E,14Z-eicosatetraenoic acid. (The chirality of the hydroperoxy and hydroxyl residues at positions 11 and 12 in the eicosatetraenoic acids are predicted based on studies defining the chirality of the arachdionic metabolites made by these enzymes.)


20-Hydroxyeicosatetraenoic acid, Metabolism
Since the prostaglandin and thromboxane metabolites of 20-HETE lack the platelet-stimulating activities to their prostaglandin and thromboxane precursors and since the 12-hydroxy and 11-hydroxy metabolites of 20-HETE may also be inactive, these metabolic pathways appear to function in inactivating 20-HETE with respect to the platelet system. However, the 20-hydroxy prostaglandin metabolites are able to contract rat aorta rings and thereby could contribute to the hypertensive actions of 20-HETE.


20-Hydroxyeicosatetraenoic acid, Metabolism
Cultured smooth muscle and endothelial cells from mouse brain microvasculature oxidize 20-HETE to its 20-carboxy analog, 20-carboxy- 5Z,8Z,11Z,14Z-eicosatetraenoic acid, then to 18-carboxy-5Z,8Z,10Z,14Z-octadecatetraenoic acid, and then to the further chain-shortened dicarboxylic acid, 16-carboxy-5Z,8Z,10E-hexadecatrrenoic acid, in a series of Beta oxidation reactions. These shortening pathways also are likely to serve in inactivating 20-HETE, although the initial product of this shortening pathway, 20-carboxy-HETE, dilates coronary microvessels in the pig heart and thereby could serve to antagonize the vasoconstrictor actions of 20-HETE, at least in this organ and species. Coronary artery endothelial cells  isolated from pigs incorporate 20-HETE primarily into the sn-2 position of phospholipids through a coenzyme A-dependent process. It is likely, although not yet shown, that these mouse and pig 20-HETE metabolizing pathways also occur in humans.


20-Hydroxyeicosatetraenoic acid, Tissue distribution of 20-HETE-producing enzymes and/or activity
20-HETE-synthesizng enzymes are widely distributed to liver, kidney, brain, lung, intestine and blood vessels. In most vascular systems, 20-HETE synthesizing activity is limited to vascular smooth muscle of small blood vessels with little or no such activity in the vessel's endothelial cells or in large blood vessels. However, both the smooth muscle and endothelial cells obtained from mouse brain microvasculature, produce 20-HETE in culture.


20-Hydroxyeicosatetraenoic acid, Tissue distribution of 20-HETE-producing enzymes and/or activity
20-HETE is produced by human neutrophils and platelets and by the ascending tubule cells in the medulla as well the pre-glomerular arterioles and certain other localized areas of the rabbit kidney.


20-Hydroxyeicosatetraenoic acid, Vascular-related activities, Rodent Studies, Blood vessel contraction
In various rodent models, 20-HETE, at low concentrations (<50 nanomolar), acts to constrict arteries by sensitizing (i.e. increasing) the contraction responses of these artery's smooth muscle cells to other contracting agents such as alpha adrenergic agonists, vasopressin, endothelin, and a product of renin angiotensin system, angiotensin II.


20-Hydroxyeicosatetraenoic acid, Vascular-related activities, Rodent Studies, Blood vessel contraction
20-HETE has a particularly complex interaction with the renin angiotensin system: angiotensin II stimulates the preglomerular microvessels of the rat kidney to produce 20-HETE; this production is required for angiotensin II to exert its full constrictor effects; and 20-HETE induces transcription of the enzyme which converts angiotensin I to angiotensin II, i.e. angiotensin-converting enzyme. Other agents such as Androgens and alpha adrenergic compounds such as norepinephrine. likewise stimulate 20-HETE production and have vasoconstrictive actions which are enhanced by 20-HETE. These circular or positive feedback interactions may serve to perpetuate vasoconstrictor responses.


20-Hydroxyeicosatetraenoic acid, Vascular-related activities, Rodent Studies, Blood vessel contraction
Again in rodent models, 20-HETE acts to block Calcium-activated potassium channels to promote the entry of ionic calcium into vascular smooth muscle cells through the L-type calcium channel; the attendant rise in intracellular calcium triggers these muscles to contract.


20-Hydroxyeicosatetraenoic acid, Vascular-related activities, Rodent Studies, Blood vessel contraction
Studies in rats also indicate that in vascular endothelial cells 20-HETE inhibits the association of the nitric oxide-producing enzyme, endothelial nitric oxide synthase (eNOS) with heat shock protein 90; this inhibits the ability of eNOS to become activated. The endothelial cells become dysfunctional in exhibiting decreased ability to produce the vasodilating agent, nitric oxide, and in containing elevated levels of a potentially injurious oxygen radical, superoxide anion; the blood vessels to which these dysfunctional endothelial cells belong are less able to dilate in response to the vasodilator, acetylcholine.


20-Hydroxyeicosatetraenoic acid, Vascular-related activities, Rodent Studies, Blood vessel contraction
20-HETE can also constrict rodent (and human) artery preparations by directly activating the receptor for thromboxane A2. While significantly less potent than thromboxane A2 in activating this receptor, studies on rat and human cerebral artery preparations indicate that increased blood flow through these arteries triggers production of 20-HETE which in turn binds to thromboxane receptors to constrict these vessels and thereby reduce their blood blow. Acting in the latter capacity, 20-HETE, it is proposed, functions as a mediator regulating blood flow to the brain.


20-Hydroxyeicosatetraenoic acid, Vascular-related activities, Rodent Studies, Blood vessel contraction
These vasoconstrictor effects of 20-HETE can reduce blood flow to specific parts of the body, not only to brain (see previous paragraph) but also to kidney, liver, heart and other organs, as well as to portions of these organs; they can also contribute to systemic hypertension as well as to the physiological and pathological effects of thromboxane receptor-activation  .


20-Hydroxyeicosatetraenoic acid, Vascular-related activities, Rodent Studies, Blood vessel injury
Sprague Dawley rats that underwent balloon injury of the common carotid artery exhibited elevated levels of CYP4A enzyme immunostaining in the smooth muscle of the injured arteries as well as elevated levels of 20-HETE in the injured arteries. Inhibition of 20-HETE production by two different agents greatly reduced the vascular intima hyperplasia and vascular remodeling that occurred after balloon injury. The studies suggest that the increase in expression of CYP4A and production of 20-HETE contribute to vascular intima growth, remolding, and thereby healing of injured rat carotid arteries.


20-Hydroxyeicosatetraenoic acid, Vascular-related activities, Rodent Studies, Blood vessel thrombosis
In the C57BL/6 mouse laboratory model, 20-HETE pretreatment accelerates the development of thrombosis and reduces blood flow caused by the Thrombosis-inducing agent, ferric chloride, in the common carotid and femoral arteries; companion studies on human umbilical vein endothelial cells indicate that 20-HETE stimulates the activation of Extracellular signal-regulated kinases to cause ERK-dependent and L-type calcium channel-dependent release of von Willebrand factor which in turn stimulates the adhesion of platelets to the endothelial cells. The endothelial, platelet, and pro-clotting actions of 20-HETE may contribute to its ability to disrupt blood flood to tissues.


20-Hydroxyeicosatetraenoic acid, Vascular-related activities, Rodent Studies, Renal absorption
In animal models, 20-HETE stimulates the activation of protein kinase C in the epithelial cells of the proximal tubules of the kidney; the kinase then phosphorylates and thereby inhibits the Na+/K+-ATPase and concurrently also blocks the Na-K-Cl cotransporter and 70 pS K+ channel in the thick Ascending limb of loop of Henle (TALH); these effects reduce the absorption of sodium and fluids in the nephron and thereby tend to reduce blood pressure.


20-Hydroxyeicosatetraenoic acid, Vascular-related activities, Rodent Studies, Hypertension
As indicated above, 20-HETE may raise blood pressure by constricting arterial blood vessels but also may lower blood pressure by promoting the loss of sodium and fluids in the kidneys. The effects of 20-HETE therefore are complex, as indicated in studies of the following animal models. Many of these models appear relevant to hypertension in humans in that they parallel the human disease, i.e. men have higher rates of hypertension than women, and women with increased levels of androgens (e.g. postmenopausal women and women with polycystic ovarian disease) and higher rates of hypertension.


20-Hydroxyeicosatetraenoic acid, Vascular-related activities, Rodent Studies, Hypertension
Spontaneously hypertensive rats exhibit elevated levels of CYP4A2 and 20-HETE; blockade of 20-HETE production lowers blood pressure in this model. The effect is particularly well seen in female rats: aging post-menopausal but not pre-menopausal female spontaneously hypertensive rats exhibit highly significant falls in blood pressure when treated with non-selective or selective inhibitors of CYP-induced 20-HETE production.


20-Hydroxyeicosatetraenoic acid, Vascular-related activities, Rodent Studies, Hypertension
Dahl salt-sensitive rats develop hypertension that develops more quickly and exacerbated by high intake of salt (sodium chloride) and ameliorated by low salt intake. In this model, rats exhibit an up-regulated CYP4A/20-HETE pathway within their cerebral vasculature and vascular endothelial cell overproduction of reactive oxygen species that in turn stimulates the CYp4A/20-HETE pathway. Non -selective and non-selective inhibitors of CYP4A and 20-HETE production reduce hypertension in this model. The hypertension in this model is more severe in male rats and appears to be mediated at least in part by vasopressin, the renin-angiotensin system, and androgens.


20-Hydroxyeicosatetraenoic acid, Vascular-related activities, Rodent Studies, Hypertension
Lewis rats (see Laboratory rat models) that had one kidney removed and then fed a high salt diet are hypertensive.


20-Hydroxyeicosatetraenoic acid, Vascular-related activities, Rodent Studies, Hypertension
Kidney medullary interstitial infusion of an inhibitor of 20-HETE production reduced the formation of 20-HETE in the outer medulla of the infused kidney, had no effect on the production of 20-HETE in the cortex of the infused kidney, and produced a mean arterial pressure rise from 115 at baseline to 142 mm of mercury; this study indicates that the hypertensive versus hypotensive effects of 20-HETE depend not only on the organ of its production but also, with respect to the kidney, the site within the organ where it is produced.


20-Hydroxyeicosatetraenoic acid, Vascular-related activities, Rodent Studies, Hypertension
Androgen treatment causes hypertension in normal male and female rats; this hypertensive response is greatly reduced by diverse inhibitors of Cyp4a and 20-HETE production.


20-Hydroxyeicosatetraenoic acid, Vascular-related activities, Rodent Studies, Hypertension
Cyp4a12-transgenic mice overexpressing Cyp4a12 develop androgen-independent hypertension that is associated with increased levels of 20-HETE; this hypertension is fully reversible by treatment with a Cyp4a selective inhibitor of 20-HETE production.


20-Hydroxyeicosatetraenoic acid, Vascular-related activities, Rodent Studies, Hypertension
Mice depleted of Cyp4a14 by gene knockout (Cyp4a14(-/-) mice develop male-specific, androgen-dependent hypertension. This seemingly paradoxical result is due to the  overexpression of Cyp4a12a; the knockout of Cyp4a14 (Cyp4a14 does not produce 20-HETE) leads to the overexpression of the 20-HETE-producing cytochrome, Cyp4a149(-/-), and consequent overproduction of 20-HETE.


20-Hydroxyeicosatetraenoic acid, Vascular-related activities, Rodent Studies, Hypertension
The model involves increased plasma androgens, increased vascular and urinary levels of 20-HETE, relief of hypertension by castration, and hypertension which is driven by excessive fluid reabsorption in the kidney's proximal tubule secondary to the overexpression of Sodium–hydrogen antiporter 3; these effects are presumed but not yet shown to be due to the overproduction of 20-HETE. The Cyp4a12-transgenic model (above) is referred to in support of this presumption.


20-Hydroxyeicosatetraenoic acid, Vascular-related activities, Rodent Studies, Hypertension
Mice depleted of Cyp4a10 maintain normal blood pressure on a low salt diet but become hypertensive on normal or high salt diets; this paradoxical result appears due to a decrease in kidney levels of Cyp2C44 caused by the loss of Cyp4a10. Cyp2C44 metabolizes arachidonic acid a family of vasodilation-inducing and anti-hypertensive products, the Epoxyeicosatrienoic acids (EETs).


20-Hydroxyeicosatetraenoic acid, Vascular-related activities, Rodent Studies, Hypertension
The model involves normal levels of 20-HETE, reduced expression of Cyp2c44, reduced levels of EETs, and deficiencies in kidney tubule absorption of sodium regulated by EETs, and the normalization of hypertensive blood pressure by increasing expression of Cyp2c44 by treating the mice with an inducer of its expression, an activator of PPARα.


20-Hydroxyeicosatetraenoic acid, Other activities
20-HETE activates the mouse and human transient receptor potential cation channel subfamily V member 1 (TRPV1, also known as the capsaicin receptor and the vanilloid receptor 1), and through this receptor, cultured dorsal root ganglion cells taken from mice.


20-Hydroxyeicosatetraenoic acid, Human studies, Genetic studies, CYP4A11 polymorphism
Human CYP4A11 has 72.69% amino acid identity with murine cyp4a14 and 73.02% identity with murine cyp4a10 suggesting that it plays a role in humans similar to that of cyp4a14 and/or cyp4a10 in mice. The association of hypertension with defective CYP4A11 in humans as indicated below seems to parallel the hypertension associated with Cyp4a14 gene knockout in mice (see above section on genetic models).


20-Hydroxyeicosatetraenoic acid, Human studies, Genetic studies, CYP4A11 polymorphism
The gene polymorphism rs1126742 variant of CYP4A11 switches thymidine to cytosine at nucleotide 8590 [


20-Hydroxyeicosatetraenoic acid, Human studies, Genetic studies, CYP4A11 polymorphism
T8590C] and leads to a phenylalanine-to-serine substitution at amino acid 434); this F434S variant has significantly reduced ability to ω-oxidize arachidonic acid to 20-HETE and has been associated with essential hypertension in: 512 white males from Tennessee (Odds ratio=2.31); 1538 males and females from the Framingham Heart Study (Odds ratio=1.23); males but not females in 732 black Americans with hypertensive renal disease participating in the African American Study of Kidney Disease; males in a sample of 507 individuals in Japan and in the third MONICA (MONitoring trends and determinants In Cardiovascular disease survey of 1397 individuals the homozygous C8590C genotype to the homozygous T8590T genotype with odds ratios of 3.31 for all subjects, 4.30 for males 2.93 for women);


20-Hydroxyeicosatetraenoic acid, Human studies, Genetic studies, CYP4A11 polymorphism
A study of 1501 participants recruited from the Tanno-Sobetsu Study found that the variant -845G in the promoter region of CYP411 (−845A is the predominant genotype) is associated with reduced transcription of CYP411 as well as with hypertension (odds ratio of homozygous and heterozygous -845G genotype versus homozygous -845A was 1.42);


20-Hydroxyeicosatetraenoic acid, Human studies, Genetic studies, CYP4A11 polymorphism
A haplotype tagging single-nucleotide polymorphism (SNP) (see Tag SNP) variant of CYP4A11, C296T (cytosine to thymine at position 296), was associated with a significantly increased risk of ischemic stroke (adjusted odds ratio of 1.50 in comparing homozygous and heterozygous C296T subjects to homozygous C286C subjects) in >2000 individuals taken from the Han Chinese population. The effect of the −296C>T single base pair substitution on baseline CYP411 transcriptional activity was not significant, suggesting that this polymorphism may not be the causal variant but instead may be in linkage disequilibrium with the causal variant. Regardless, this SNP may serve as a genetic marker for large vessel disease stroke risk in this population.


20-Hydroxyeicosatetraenoic acid, Human studies, Genetic studies, CYP4F2 polymorphism
The T allele at rs2108622, which has been designated as CYP4F2*3 in the Human CYP Allele Nomenclature Database by the Pharmacogene Variation Consortium, produces the CYP4F2 enzyme with methionine residue instead of valine at position 433 (the Val433Met variant), a single-nucleotide polymorphism (1347C>T; NM_001082.5:c.1297G>A; p.  Val433Met; rs2108622). This variant of the CYP4F2 enzyme has reduced capacity to metabolize arachidonic acid to 20-HETE but increased urinary excretion of 20-HETE.


20-Hydroxyeicosatetraenoic acid, Human studies, Genetic studies, CYP4F2 polymorphism
Studies found that: a) among 161 hypertensive and 74 normotensive subjects in Australia, the incidence of the Val433Met variant was significantly increased in the hypertensive subjects; b) among a large number of Swedish patients enrolled and monitored over 10 years in the cardiovascular cohort of the Malmö Diet and Cancer Study only males with this variant exhibited hypertension; c) among several hundred subjects in India, the variant was associated with hypertension; and d) in comparing 249 patients with hypertension to 238 age-matched controls in Japan, the variant was not associated with hypertension. The maintenance of the lower blood pressure that followed diet-induced weight loss was more difficult for carriers of the Val433Met variant and may be related to increased arterial stiffness and increased 20-HETE synthesis.


20-Hydroxyeicosatetraenoic acid, Human studies, Genetic studies, CYP4F2 polymorphism
The Val433Met variant is also associated with an increased incidence of cerebral infarction (i.e. ischemic stroke) in a study of 175 subjects with infarction compared to 246 control subjects in Japan, in 507 stroke patients compared to 487 age- and sex-matched 487 controls in India, and in males but not females in a study of 558 patients compared to 557 controls in China. The variant is associated with myocardial infarction in a study of 507 patients compared to 487 age-


20-Hydroxyeicosatetraenoic acid, Human studies, Genetic studies, CYP4F2 polymorphism
and sex-matched controls in India, in males but not females in a study of 234 patients compared to 248 control subjects in Japan, and in male but not female patients in Sweden enrolled in the cardiovascular cohort of the Malmo Diet and Cancer Study. The incidences of cerebral and myocardial infarction in these studies appears to be independent of hypertension. (The platelets of individuals heterozygous or homozygous for the Val433Met variant exhibit increased platelet aggregation responses to epinephrine. This platelet hyper-responsiveness to epinephrine, particularly if also exhibited to other platelet-aggregating agents, could contribute to cerebral and coronary infarctions.)


20-Hydroxyeicosatetraenoic acid, Human studies, Genetic studies, CYP4F2 polymorphism
The Single-nucleotide polymorphism rs1558139 guanine to cytosine variant in an intron of CYP4F2 is associated with essential hypertension in men only in a study of 249 hypertensive versus 238 age-matched controls in Japan. The impact of this variant on CYP4F2 expression is not known.


20-Hydroxyeicosatetraenoic acid, Human studies, Genetic studies, CYP4F2 polymorphism
Researchers have identified at least 3 more single-nucleotide polymorphisms of CYP4F2 (2024C>G P85A; 80 C>T A27V rs771576634; 139C>T R47C rs115517770) which may affect conversion of arachidonic acid to HETE-20.


20-Hydroxyeicosatetraenoic acid, Human studies, Genetic studies, CYP2U1 mutations
A mutation (c.947A>T) in CYP2U1 has been associated with a small number of patients with Hereditary spastic paraplegia in that it segregates with the disease at the homozygous state in two afflicted families. The mutation affects an amino acid (p.Asp316Val) highly conserved among CYP2U1 orthologs as well as other cytochrome P450 proteins; the p.Asp314Val mutation is located in the enzyme's functional domain, is predicted to be damaging to the enzyme's activity, and is associated with mitochondria dysfunction. A second homozygous enzyme-disabling mutation has been identified in CYP2U1, c.1A>C/p.Met1?, that is associated with <1% of hereditary spastic paraplegia sufferers. While the role of 20-HETE in these mutations has not been established, the reduction in 20-HETE production and thereby 20-HETE's activation of the TRPV1 receptor in nerve tissues, it is hypothesized, may contribute to the disease.


20-Hydroxyeicosatetraenoic acid, Human studies, Cancer, Breast cancer
Two human breast cancer cell lines, T47D and BT-474, made to overexpress CYP4Z1 by transfection overexpress messenger RNA for and overproduce vascular endothelial growth factor A while under expressing message and protein for tissue inhibitor of metalloproteinase-2. T47D cells that overexpress CYP4Z1 also overproduce 20-HETE and when transplanted into athymic Balb/c mice show a greater increase in tumor weight and vascularity compared to control T47D cells; these increases are prevented by an inhibitor of 20-HETE production. Isoliquiritigenin, a proposed drug for treating cancer, cause cultured MDA-MB-231 and MCF-7 human breast cancer cells to die by triggering apoptosis.


20-Hydroxyeicosatetraenoic acid, Human studies, Cancer, Breast cancer
Among its many other effects, the drug caused these cells to decrease their levels of 20-HETE in vitro; the addition of 20-HETE to these cultures rescued the cells from apoptosis. Isoliquiritigenin also inhibits the in vivo lung metastasis of MDA-MB-231 cell transplants while concurrently decreasing the tumor's levels of 20-HETE. The growth of MDA-MB-231 cells implanted into athymic nude female mice as well as the cells' production of a large variety of agents stimulating vascularization including vascular endothelial growth factor were inhibited by treating the mice with an inhibitor of 20-HETE production.


20-Hydroxyeicosatetraenoic acid, Human studies, Cancer, Breast cancer
Messenger RNAs not only for CYP4Z2 but also for CYP4A11, CYP4A22, CYP4F2, and CYP4F3 are more highly expressed in samples of human breast cancer tumors compared to normal breast tissue. The Three prime untranslated regions (3'UTRs) of the CYP4Z1 gene and its Pseudogene, CYP4Z2P, share several miRNA-binding sites, including those for miR-211, miR-125a-3p, miR-197, miR-1226, and miR-204'.


20-Hydroxyeicosatetraenoic acid, Human studies, Cancer, Breast cancer
Since these miRNA's reduce the translation of CYP4Z1, the expression of CYP4Z2P can bind these miRNAs to reduce their interference with CYP4Z1 and thereby increase the production of CYP4Z1 protein and perhaps 20-HETE; indeed, force expression of these 3'UTRs promoted in vitro tumor angiogenesis in breast cancer cells partly via miRNA-dependent activation of the phosphoinositide 3-kinase-MAPK/ERK pathway and thereby stimulating the production of vascular endothelium growth factor and possibly other endothelium growth factors. Taken together, these pre-clinical studies suggest that 20-HETE made by one or more of the cited cytochrome P450 enzymes may contribute to the progression of breast cancer by promoting its survival, growth, and vascular endothelial growth factor-induced neovascularization.


20-Hydroxyeicosatetraenoic acid, Human studies, Cancer, Other cancers
20-HETE stimulated the proliferation of cultured human brain Glioma cell line U251 and, when forced to overexpress CYP4Z1 by gene transfection, overproduced 20-HETE and exhibited a dramatically increased rate of growth that was blocked by inhibiting the cells from producing 20-HETE. A similar set of findings was found with human non-small cell lung cancer cells. A selective inhibitor of 20-HETE synthesis and a 20-HETE antagonist reduced the growth of two human kidney cancer 786-O and 769-P cell lines in culture; the 20-HETE antagonist also inhibited the growth of 786-O cells transplanted into athymic nude mice.


20-Hydroxyeicosatetraenoic acid, Human studies, Cancer, Other cancers
Messenger RNAs for CYP4A11, CYP4A22, CYP4F2, and/or CYP4F3 are more highly expressed in ovary, colon, thyroid, lung, ovary, cancers compared to their normal tissue counterparts; in ovarian cancer, this higher expression is associated with an increased level of CYP4F2 protein expression and an increased ability to metabolize arachidonic acid to 20-HETE. Ovarian cancers also overexpress CYP4Z1 mRNA protein; this overexpression is associated with a poorer disease outcome.


20-Hydroxyeicosatetraenoic acid, Human studies, Cancer, Other cancers
While these studies suggest that CYP4A11, CYP4A22, CYP4F2, and/or CYP4F3 produce 20-HETE which in turn promotes the growth of the cited cancers in model systems and therefore may do so in the human cancers, this suggestion clearly needs much further study. For example, an inhibitor of 20-HETE production blocks the growth of human brain U251 glioma cells in culture; since these cells could not be shown to produce 20-HETE, it was proposed that some other metabolite may by the inhibitor's targeted cytochrome enzymes was responsible for maintaining  these cells growth. It is also possible that any such inhibitor has off-target effects that are responsible for its actions.


20-Hydroxyeicosatetraenoic acid, Human studies, Platelet aggregation
20-HETE inhibits the aggregation of human platelets by competing with arachidonic acid for the enzymes that produce prostaglandin H2 and thromboxane A2. These products are formed in response to platelet stimulation and then act through the thromboxane receptor to mediate and/or promote the ensuing platelet aggregation response to most stimuli. The platelets metabolize 20-HETE to the 20-hydroxy analogs of prostaglandin H2 and thromboxane A2, products that are essentially inactive in platelets, while consequently form less of the arachidonic acid-derived prostaglandin and thromboxane products. In addition, 20-HETE itself blocks prostaglandin and thromboxane metabolites from interacting with the thromboxane receptor. Both effects, i.e. replacement of prostaglandin and thromboxane production with platelet-inactive products and thromboxane A2 receptor blockade, are responsible for 20-HETE's platelet aggregation-inhibiting action. However, the platelet anti-aggregating activity of 20-HETE requires micromolar levels and therefore may be more of a pharmacological than physiological activity.


20-Hydroxyeicosatetraenoic acid, Human studies, Vasculature
20-HETE constricts human artery preparations by directly activating the receptor for thromboxane A2. While significantly less potent than thromboxane A2 in activating this receptor, studies on human cerebral artery preparations indicate that increased blood flow through these arteries triggers production of 20-HETE which in turn binds to thromboxane receptors to constrict these vessels and thereby reduce their blood blow. Acting in the latter capacity, 20-HETE, it is proposed, functions as a mediator regulating blood flow to the human brain.


20-Hydroxyeicosatetraenoic acid, Human studies, Metabolic syndrome
One study found that 30 patients with the metabolic syndrome exhibited significantly elevated levels of plasma and urinary 20-HETE compared to matched controls; women with the syndrome had particularly higher urinary 20-HETE levels.


20-N
20-N is a symbolic abbreviation used to denote the date of death of two of the best known and controversial figures in 20th-century Spanish history. The first date, 20 November 1936, near the end of the first year of the Spanish Civil War, marks the execution in Alicante of 33-year-old José Antonio Primo de Rivera, the founder of the fascist party, Falange Española (Spanish Phalanx), who became extolled as a cult figure during the years of post-civil war Francoist Spain led by Francisco Franco.


20-N
The second date, 39 years later, is 20 November 1975, when Generalísimo Franco – aged 82, and having ruled Spain for close to four decades as its dictator, or as he called himself, caudillo (Spanish for leader) – died in bed following a lengthy illness. The date continues to be commemorated by far-right groups which mark it by organizing public demonstrations.


20-Pipe Well
The 20 Pipe Well (German: 20-Röhren-Brunnen) is a water well in the Rhineland-Palatinate village of Altleiningen in the northeast of the Palatinate Forest. The well was probably driven around 1600 and was used originally to supply drinking water to Altleiningen Castle on the hill above. Its present design dates to 1855.


20-Pipe Well, Geography
In the vicinity of the well is the Eckbach stream, which has its own source four kilometres upstream and is a left tributary of the River Rhine. It picks up the water from the 20 Pipe Well, which today supplies the greatest amount of water to the stream. Running past the fountain is the 23-kilometre-long Eckbach Mill Path, which begins at the source of the Eckbach in Hertlingshausen and follows it downstream to Dirmstein in the Upper Rhine Plain.


20-Pipe Well, Layout
The well is fed by the strongest fracture spring (Spaltenquelle) in the Palatinate. The water rises from a fracture and is initially impounded into two large well chambers before being pouring out of 20 parallel pipes. The amount of water is controlled by a system of impounding the ground water which was very well thought through for its day.


20-Pipe Well, Layout
Above the well is a protected inscription tablet of sandstone dating to 1855, when the well was given its present appearance; it was also rebuilt in the 1980s, undergoing a thorough renovation including some new components. The inscription is an imaginary dialogue between the walker (W) and the well (B):


20-Pipe Well, Layout
Siehe, Wanderer: Gottes Brünnlein hat Wasser die Fülle! W.: Ja, Brünnlein, du hast Wassers die Füll; Gibst Jedem zu trinken, der da will. B.: Der reiche Gott hat mirs gegeben; Machs mir nur nach, so wirst du leben! W.: Was bleibt dann aber mir zuletzt? B.: Ein Wasser, das ewig dich ergötzt.


20-Pipe Well, Layout
See, walker: God's little spring is overflowing with water! W.: Yes, little spring, you're full of water; Give it to everyone who wants some, so they may drink. B.: God, who is generous, gave it to me; Just do the same and you will live! W.: So what, then, will I have in the end? B.: A kind of water that fills you for ever.


20-Pipe Well, History
The well was built at the behest of the counts of Leiningen in order to improve the water supply to their family seat, the castle of Altleiningen, and to ensure a permanent supply. There are no records of the exact year of construction, but historians estimate that it dates to around 1600.


20-Solagii Istiqloliyati Tojikiston
20-Solagii Istiqloliyati Tojikiston (Russian: 20-летия Независимости Республики Таджикистан; Tajik: Ҷамоати 20-солагии Истиқлолияти Тоҷикистон, literal translation: "20 years independence of Tajikistan", formerly: Komsomolobod) is a jamoat in Tajikistan. It is located in Farkhor District in Khatlon Region. The jamoat has a total population of 14,736 (2015).


20-Year Strategy for the Irish Language 2010–2030
The 20-Year Strategy for the Irish Language 2010–2030 (Irish: Straitéis 20 Bliain don Ghaeilge 2010–2030) is a 20-year strategy launched by the Government of Ireland on 20 December 2010 and which will be in operation until December 2030. The main aim of the Strategy is to increase the number of daily Irish speakers in Ireland to 250,000 by 2030. In the 2011 census this number was at 77,185. In the 2016 census it had dropped to 73,803.


20-Year Strategy for the Irish Language 2010–2030
In June 2018 Minister of State for the Irish Language, Gaeltacht and the Islands  Joe McHugh TD launched the first cross-governmental Action Plan for the 20-Year Strategy for the Irish Language 2010-2030 which is operating between 2018 and 2022.


20-gauge shotgun
The 20-gauge shotgun, also known as "20-bore", is a type of smooth-bore shotgun that fires a shell that is smaller in caliber (.615 in (15.6 mm)) than a 12-gauge shotgun (.729 in (18.5 mm)). It is often used by beginning shooters for target practice and for hunting small game.


20-gauge shotgun, Description
It takes 20 lead balls of the diameter of a 20-gauge shotgun bore to equal one pound, while it only takes 12 lead balls of the diameter of a 12-gauge shotgun bore to equal the same weight. A 20-gauge shotgun is more suitable for hunting certain types of game or for some hunters because it recoils less, and the guns weigh less and may be smaller.


20-gauge shotgun, Description
Regarding the yellow body tube color 20-gauge ammunition usually has, it has been reserved in SAAMI documentation saying "SAAMI has reserved  yellow for 20-gauge ammunition" "This ammunition shall have a body tube that is primarily yellow" "Yellow shall not be used for any other gauge/bore shotshell body" "No other recommendations are made as to the color of service body tubes for other gauges/bores"


20-gauge shotgun, Specifications
20-gauge shotguns are especially suitable for hunting game birds such as quail, grouse, turkey, and other game when using shot shells. A 20-gauge can also shoot slugs and buckshot and thereby become an effective deer-hunting gun. While shotguns loaded with slugs are generally less accurate than rifles, full-power shells often have better stopping power at short range due to the large mass of the projectile.


20-gauge shotgun, Performance
A usually lower weapon weight makes a 20-gauge appropriate for young, elderly, or weaker shooters who may have a difficult time carrying, aiming, and firing a larger shotgun. In addition, 20-gauge shotguns generally have less recoil than 10-, 12-, or 16-gauge versions on average, when comparing standard hunting shells, due to the lower projectile payload. These parameters make the 20-gauge more pleasant to use on extended hunting trips for small game or upland birds, even for people capable of firing magnum-power 12-gauge hunting rounds.


20-gauge shotgun, Performance
It should be noted, however, that full-power 20-gauge shells fired from a light 4.5 lb (2.0 kg) weapon will have more felt recoil than reduced-recoil 12-gauge shells fired from a heavy 8 lb (3.6 kg) weapon.


20-meter band
The 20-meter or 14-MHz amateur radio band is a portion of the shortwave radio spectrum, comprising frequencies stretching from 14.000 MHz to 14.350 MHz. The 20-meter band is widely considered among the best for long-distance communication (DXing), and is one of the most popular—and crowded—during contests. Several factors contribute to this, including the band's large size, the relatively small size of antennas tuned to it (especially as compared to antennas for the 40-meter band or the 80-meter band) and its good potential for daytime DX operation even in unfavorable propagation conditions.


20-meter band, History
The 20-meter band was first made available to amateurs in the United States by the Third National Radio Conference on October 10, 1924. The band was allocated on a worldwide basis by the International Radiotelegraph Conference inWashington, D.C., on October 4, 1927. Its frequency allocation was then 14–14.4 MHz. The allocation was reduced to 14–14.35 MHz by the International Radio Conference of Atlantic City, New Jersey 1947.


20-meter band, Band plans, Canada
Canada is part of region 2 and as such is subject to the IARU band plan. Radio Amateurs of Canada offers the bandplan below as a recommendation for use by radio amateurs in that country but it does not have the force of law and should only be considered a suggestion or guideline.


20-pair colour code (Australia)
The 20-pair colour code is a colour code used in Australia to identify individual conductors in a kind of electrical telecommunication wiring for indoor use, known as twisted pair cables. The colours are applied to the insulation that covers each conductor. The first colour is chosen from one group of five colours.


20-pair colour code (Australia)
The combinations are also shown in the table below showing the colour for each wire ("1" and "2") and the pair number.


20-pair colour code (Australia)
Note that there is no colour called "Grey". The correct colour terminology is "Slate".


20-point agreement
The 20-point agreement, or the 20-point memorandum, is a list of 20 points drawn up by North Borneo, proposing terms for its incorporation into the new federation as the State of Sabah, during negotiations prior to the formation of Malaysia. In the Malaysia Bill of the Malaysia Agreement some of the twenty points were incorporated, to varying degrees, into what became the Constitution of Malaysia; others were merely accepted orally, thus not gaining legal status. The 20-point agreement often serves as a focal point amongst those who argue that Sabah's rights within the Federation have been eroded over time.


20-point agreement, Background
Under an agreement signed between Great Britain and the Federation of Malaya the issue of self-determination with respect to the peoples of North Borneo and Sarawak formed a challenge to the formation of the Federation of Malaysia. A Joint Statement issued by the British and Malayan Federal Governments on 23 November 1961 announced that before coming to any final decision it was necessary to ascertain the views of the peoples of North Borneo and Sarawak. It was decided to set up a commission to carry out that task and to make recommendations.


20-point agreement, Background
The British Government, working with the Federation of Malaya Government, appointed a Commission of Enquiry for North Borneo and Sarawak in January 1962 to determine if the people supported the proposal to create a Federation of Malaysia. The five-man team, which comprised two Malayans and three British representatives, was headed by Lord Cobbold. An inter-governmental committee (The Lansdowne Committee) was appointed to work out the final details of the Malaysia Agreement. Lord Lansdowne served for Britain and Tun Abdul Razak, Deputy Prime Minister of the Federation of Malaya served for Malaya.


20-point agreement, Background
The 20 points were written with a view to safeguarding the interests, rights, and autonomy of the people of North Borneo upon the formation of the federation of Malaysia. A similar proposal, with certain differences in content, was made by Sarawak, and is commonly referred to as the 18-point agreement.


20-point agreement, Background
Attention is often drawn to these memoranda by those who believe that their principles were not subsequently adhered to after federation. There have been numerous calls for the 20-point memorandum to be reviewed so as to take into account social, economic, and political changes over time.


20-point agreement, The 20 points, Point 1: Religion
While there was no objection to Islam being the national religion of Malaysia, there should be no State religion in North Borneo, and the provisions relating to Islam in the present Constitution of Malaya should not apply to North Borneo.


20-point agreement, The 20 points, Point 3: Constitution
Whilst accepting that the present Constitution of the Federation of Malaya should form the basis of the Constitution of Malaysia, the Constitution of Malaysia should be a completely new document drafted and agreed in the light of a free association of states and should not be a series of amendments to a Constitution drafted and agreed by different states in totally different circumstances. A new Constitution for North Borneo was of course essential.


20-point agreement, The 20 points, Point 4: Head of Federation
The Head of State in North Borneo should not be eligible for election as Head of the Federation.


20-point agreement, The 20 points, Point 6: Immigration
Control over immigration into any part of Malaysia from outside should rest with the Central Government but entry into North Borneo should also require the approval of the State Government. The Federal Government should not be able to veto the entry of persons into North Borneo for State Government purposes except on strictly security grounds. North Borneo should have unfettered control over the movements of persons other than those in Federal Government employ from other parts of Malaysia into North Borneo.


20-point agreement, The 20 points, Point 7: Right of Secession
There should be no right to secede from the Federation


20-point agreement, The 20 points, Point 8: Borneanisation
Borneanisation of the public service should proceed as quickly as possible.


20-point agreement, The 20 points, Point 9: British Officers
Every effort should be made to encourage British Officers to remain in the public service until their places can be taken by suitably qualified people from North Borneo.


20-point agreement, The 20 points, Point 10: Citizenship
The recommendation in paragraph 148(k) of the Report of the Cobbold Commission should govern the citizenship rights in the Federation of North Borneo subject to the following amendments:


20-point agreement, The 20 points, Point 11: Tariffs and Finance
North Borneo should retain control of its own finance, development and tariff, and should have the right to work up its own taxation and to raise loans on its own credit.


20-point agreement, The 20 points, Point 12: Special position of indigenous races
In principle the indigenous races of North Borneo should enjoy special rights analogous to those enjoyed by Malays in Malaya, but the present Malaya formula in this regard is not necessarily applicable in North Borneo.


20-point agreement, The 20 points, Point 14: Transitional period
This should be seven years and during such period legislative power must be left with the State of North Borneo by the Constitution and not be merely delegated to the State Government by the Federal Government.


20-point agreement, The 20 points, Point 15: Education
The existing educational system of North Borneo should be maintained and for this reason it should be under state control.


20-point agreement, The 20 points, Point 16: Constitutional safeguards
No amendment modification or withdrawal of any special safeguard granted to North Borneo should be made by the Central Government without the positive concurrence of the Government of the State of North Borneo


20-point agreement, The 20 points, Point 16: Constitutional safeguards
The power of amending the Constitution of the State of North Borneo should belong exclusively to the people in the state. (Note: The United Party, The Democratic Party and the Pasok Momogun Party considered that a three-fourths majority would be required in order to effect any amendment to the Federal and State Constitutions whereas the UNKO and USNO considered a two-thirds majority would be sufficient.)


20-point agreement, The 20 points, Point 17: Representation in Federal Parliament
This should take account not only of the population of North Borneo but also of its size and potentialities and in any case should not be less than that of Singapore.


20-point agreement, The 20 points, Point 20: Land, Forests, Local Government, etc.
The provisions in the Constitution of the Federation in respect of the powers of the National Land Council should not apply in North Borneo. Likewise, the National Council for Local Government should not apply in North Borneo.


20-point agreement, Controversies, Point 7: Right of Secession
Article 2 of the Constitution of Malaysia states that the Parliament of Malaysia has the right to change the state boundaries or to admit any new states into the federation. However, there is no provision about the secession of states from the federation. However, former International Islamic University Malaysia (PIHE) academic, Dr Abdul Aziz Bari, said that Article 2 of the Constitution also implies that the Malaysian Parliament has the final say on the secession of a state from the federation, as it did to Singapore in 1965. Besides, any suggestions about secession of Sabah and Sarawak from Malaysia would be punishable under Sedition Act.


20-point agreement, Controversies, Point 7: Right of Secession
Dr Jeniri Amir from Universiti Malaysia Sarawak (UNIMAS) stated that Sarawak and Sabah has no right to secede from the federation according to Point 7. However, a separatist group led by Doris Jones said that the meaning of the word "should" as in "There should be no right to secede from the Federation" is only a recommendation as opposed to "shall" which implies a command.


20-point agreement, Controversies, Point 18: Name of Head of State
In the Malaysia Agreement, the meaning of the term "Governor" included the title of the Head of State of Sabah, which was "Yang di-Pertua Negara". This term was incorporated into the Constitution of Malaysia from 1963 to 1976. However, the Sarawak head of state was named "Yang di-Pertua Negeri" from 1963.


20-point agreement, Controversies, Point 18: Name of Head of State
On 27 August 1976, under Article 160 of the Constitution of Malaysia, the term "Governor" was abolished and replaced with "Yang di-Pertua Negeri". This effectively ended the title of "Yang di-Pertua Negara" of Sabah. The Malay translation of the term "State" of Sabah and Sarawak has been "Negeri" (Federated states) instead of "Negara" (Nation) since 1963.


20-point agreement, Controversies, Point 18: Name of Head of State
Nevertherless, some groups argue that Sabah and Sarawak should be called "Negara" (Nation), and the head of state called "Yang di-Pertua Negara", on the basis that Sarawak achieved independence on 22 July 1963 and Sabah achieved independence on 31 August 1963 before forming Malaysia together with Federation of Malaya on 16 September 1963. They believe that the head of state of Sabah being known as "Yang di-Pertua Negara" between 1963 and 1976 supports this view.


20-pounder Parrott rifle
The 20-pounder Parrott rifle, Model 1861 was a cast iron muzzle-loading rifled cannon that was adopted by the United States Army in 1861 and employed in field artillery units during the American Civil War. As with other Parrott rifles, the gun breech was reinforced by a distinctive wrought iron reinforcing band. The gun fired a 20 lb (9.1 kg) projectile to a distance of 1,900 yd (1,737 m) at an elevation of 5°. The 20-pounder Parrott rifle could fire shell, shrapnel shell (case shot), canister shot, and more rarely solid shot. In spite of the reinforcing band, the 20-pounder earned a dubious reputation for bursting without warning, killing or injuring gunners. The Confederate States of America also manufactured copies of the gun.


20-pounder Parrott rifle, Background
Robert Parker Parrott was an ordnance officer in the US Army who inspected cannons manufactured at the West Point Foundry in Cold Spring, New York. In 1836, president of the company Gouverneur Kemble persuaded Parrott to resign from the Army and join his firm. Several years before the American Civil War, gun founders grappled with the problem of rifling cannons. Bronze smoothbore cannons had windage – or space – between the round shot and the barrel. Windage caused the propellant gases from the gunpowder explosion to leak out, but it also put less stress on the gun barrel.


20-pounder Parrott rifle, Background
With rifled cannon, the ammunition was designed to expand the shell so that there was no windage between the projectile and the gun barrel. This meant that a smaller gunpowder charge could throw a rifled projectile farther, but it also meant that the gun barrel was put under greater stress. Bronze cannons infrequently burst because the metal was flexible. Cast iron was stronger than bronze, but it was also more rigid. This made cast iron guns more prone to burst at the breech or muzzle.


20-pounder Parrott rifle, Background
Bronze was too soft a metal for rifled guns. Cast iron was hard enough to take rifling but it was too brittle. Parrott's solution to this puzzle was a cast iron rifled cannon that had a wrought iron reinforcing band wrapped around the breech. When banded guns were manufactured, gravity acted on the bands as they cooled, making an uneven fit around the gun barrel. Parrott overcame the problem by slowly rotating the gun barrel while it was being cooled. The Parrott rifle was first developed in 1859–1860.


20-pounder Parrott rifle, Background
Parrott later noted of his invention, "I do not profess to think that they are the best gun in the world, but I think they were the best practical thing that could be got at the time". The U.S. government bought the first ten 10-pounder Parrott rifles on 23 May 1861. The U.S. Ordnance Department trusted Robert Parrott to such a degree that he was allowed to be the inspecting officer until the end of 1862. This was a unique arrangement since Parrott was also the manufacturer.


20-pounder Parrott rifle, Manufacture
The West Point Foundry produced about 300 20-pounder Parrott rifles between September 1861 and July 1864. The gun barrels weighted between 1,635 lb (742 kg) and 1,815 lb (823 kg). The rifling consisted of five lands and grooves of right-hand gaining twist (increasing toward the muzzle) and the caliber (bore diameter) was 3.67 in (93 mm). The 20-pounder Parrott had a reinforcing band 16.25 in (41 cm) long and 1.5 in (38 mm) thick. The Register of Inspections recorded numbers 1 through 284.


20-pounder Parrott rifle, Manufacture
However, there were gaps in the record and surviving guns have been found with numbers in the gaps. Also, there is a gun at Gettysburg National Military Park with registry number 296, so it is likely that the real number of guns produced is at least 296. The cost per gun was approximately $380. A number of the guns were designed for Navy use and had a block and pin that fitted over the cascabel (end knob). Only 15 Federal-made guns are known to have survived to the present day.


20-pounder Parrott rifle, Manufacture
The Tredegar Iron Works in the Confederacy produced 45 20-pounder Parrott rifles between August 1862 and December 1864. Like the Federal version, the guns were rifled with five grooves in a right-hand twist. The Confederate pattern differed from the Federal gun by having a reinforcing band 20 in (51 cm) long and 2 in (51 mm) thick. This resulted in the guns averaging 1,866 lb (846 kg) each, which is 51 lb (23 kg) more than the heaviest Federal pieces.


20-pounder Parrott rifle, Manufacture
The Noble Brothers & Company of Rome, Georgia contracted to manufacture 20-pounder Parrott rifles for the Confederacy, but it is not known if they were produced and none have survived. There are 14 surviving Confederate-made 20-pounder Parrott rifles of which two have markings from the Macon Arsenal and the others were made at Tredegar. The two Macon Arsenal guns have weights averaging 1,657 lb (752 kg).


20-pounder Parrott rifle, Specifications
The 20-pounder Parrott rifle had a bore (caliber) with a diameter of 3.67 in (93 mm) and fired a projectile weighing 20 lb (9.1 kg). Its gun barrel was 84 in (213 cm) long and weighed about 1,750 lb (794 kg). The gunpowder charge weighed 2.0 lb (0.9 kg) and fired the projectile with a muzzle velocity of 1,250 ft/s (381 m/s) to a distance of 1,900 yd (1,737 m) at 5° elevation. A smoothbore cannon's projectile usually retained only one-third of its muzzle velocity at 1,500 yd (1,372 m) and its round shot could be seen in the air.


20-pounder Parrott rifle, Specifications
At the same distance, a rifled projectile often retained two-thirds of its muzzle velocity and was not visible while in flight. A rifled projectile only became visible if it started to tumble out of control. Tumbling occurred when the shell failed to take the grooves inside the gun barrel or when the spin wore off in flight.


20-pounder Parrott rifle, Specifications
Rifling allowed elongated/heavier rounds to be fired. For example, smoothbore cannons of the same 3.67 caliber as the 20-pounder Parrott fired only 6 pound round shot. For example the M1841 6-pounder field gun.


20-pounder Parrott rifle, Specifications
The 20-pounder Parrott rifle was mounted on the 1,175 lb (533 kg) carriage for the M1841 12-pounder field gun. The 20-pounder Parrott rifle fired case shot (shrapnel), shell, and canister shot. The use of bolts (solid shot) was rare and it was usually not provided in the ammunition chests. Firing a shell without a fuse would achieve the same result as firing a solid shot from a rifled gun. Parrott ammunition was designed to be used. The Parrott rifles could also fire Hotchkiss ammunition, but gunners were not allowed to use Schenkl ammunition. One flaw in Parrott ammunition was the position of the sabot was at the shell's base. This meant that the final impulse on the projectile as it left the gun was on its base, possibly causing the shell to wobble in flight.


20-pounder Parrott rifle, Specifications
When firing Canister shot rifled guns were not as effective as canister fired from a 12-pounder Napoleon or a M1841 12-pounder howitzer. First, the rifled gun's 3.67-inch bore was narrower than the 12-pounder's 4.62 in (117 mm) bore and thus could fire fewer canister balls. Second, the gun's rifling caused the canister to be thrown in an irregular pattern. Union General Henry Jackson Hunt asserted that rifled guns had a canister range only half the 400 yd (366 m) effective range of canister fired from the 12-pounder Napoleon.


20-pounder Parrott rifle, Specifications
Early in the war, many Union batteries were organized with six guns of identical type. However, as will be noted, batteries armed with 20-pounder Parrott rifles often had four guns. Each gun required two 6-horse teams. The first team pulled the gun and its limber and the second team pulled the caisson (ammunition wagon). Each caisson carried two ammunition chests and the limber carried one additional ammunition chest. In addition to its guns, limbers, and caissons, each battery had two additional vehicles, a supply wagon and a portable forge.


20-pounder Parrott rifle, Specifications
The 20-pounder Parrott rifle's great weight made it difficult for a 6-horse team to pull. The guns were among the heaviest pieces that could be classified as field artillery, so few were taken along with the field armies. The 10-pounder Parrott rifle was more frequently utilized. Under normal conditions, infantry could be expected to march 15 mi (24.1 km) in six hours, while it would take an artillery battery 10 hours to march 16 mi (25.7 km).


20-pounder Parrott rifle, History
At the Battle of Antietam on 17 September 1862, the Federal Army of the Potomac employed 22 20-pounder Parrott rifles while the Confederate Army of Northern Virginia had none. The 5th New York Independent Light Artillery (Taft's) and 1st New York Light Artillery Battalion, Batteries A (Wever's), B (von Kleiser's), and C (Langner's) were all 4-gun 20-pounder Parrott batteries belonging to the V Corps. Simmonds' Battery Kentucky Light Artillery had two 20-pounder Parrott rifles, three 10-pounder Parrott rifles, and one iron 12-pounder howitzer.


20-pounder Parrott rifle, History
Simmonds' Battery and the 4-gun 20-pounder Parrott armed 2nd U.S. Artillery, Battery E (Benjamin's) served in the IX Corps. During the Battle of Fredericksburg on 13 December 1862, the 5th New York Battery and Batteries A, B, and C of the New York Battalion served in the Artillery Reserve. The Artillery Reserve was posted on the east bank of the Rappahannock River on Stafford Heights, opposite the town of Fredericksburg, Virginia.


20-pounder Parrott rifle, History
Before the Second Battle of Corinth on 3–4 October 1862, William Rosecrans built several lunettes to defend the west side of Corinth, Mississippi. Battery Phillips was 200 yd (183 m) north of Corona Female College, Battery Williams was 400 yd (366 m) northeast of Phillips, and Battery Robinett was 200 yd (183 m) north of Williams and 675 yd (617 m) west of Corinth. Battery Williams contained 30-pounder Parrott rifles while Battery Robinett was armed with three 20-pounder Parrott rifles and manned by Company C of the 1st U.S. Infantry Regiment.


20-pounder Parrott rifle, History
On the first day, Captain Henry Richardson's Battery D, 1st Missouri Light Artillery helped repel two Confederate attacks but lost one gun. On the second day, the Confederate division led by Martin E. Green routed the division of Thomas Alfred Davies in the Union right-center, but not before the Union guns in Battery Powell inflicted serious casualties. Guarding the north side of Corinth, Battery Powell was defended by three 20-pounder Parrott rifles of Richardson's battery and two M1841 24-pounder howitzers. These guns were overrun.


20-pounder Parrott rifle, History
However, the tide turned and Federal troops recaptured the position, re-manned the guns, and fired on the retreating Confederates. In the center, Dabney H. Maury's Confederate division launched an assault on David S. Stanley's Federal division. Stanley's position was buttressed by Battery Robinett which became the focus of gallant but unsuccessful Confederate attacks. Losses on both sides were heavy.


20-pounder Parrott rifle, History
Union General Quincy Adams Gillmore believed that Parrott rifles were as good as the best artillery despite their "unequal endurance". He wrote that the Parrotts were easy for gun crews to operate. Nevertheless, the 20-pounder Parrott rifles had many critics. Confederate General J. Johnston Pettigrew complained that a battery of four 20-pounder Parrotts proved to be worthless. He wrote that half their shells exploded almost as soon as they left the gun and many of the others wobbled in flight. Finally, one of the guns burst, killing one gunner and injuring two others.


20-pounder Parrott rifle, History
Confederate Major John Haskell wanted the 20-pounder Parrotts taken away from the Macon Light Artillery to spare its men possible injury. Union General Hunt protested that the 20-pounder Parrotts were "very unsatisfactory" because the shells were unreliable and dangerous to Federal troops. He noted that two of the guns burst at Antietam and one at Fredericksburg. Hunt tried to suppress the use of the 20-pounders in the Army of the Potomac. One of the guns of Taft's Battery (5th New York) burst at Gettysburg. Parrott rifles were not employed again after the Civil War.


20-sim
20-sim is commercial modeling and simulation program for multi-domain dynamic systems, which is developed by Controllab. With 20-sim, models can be entered as equations, block diagrams, bond graphs and physical components. 20-sim is widely used for modeling complex multi-domain systems and for the development of control systems.


20-sim, Use
20-sim supports four methods for modeling dynamic systems: iconic diagrams, block diagrams, bond graphs and equations. All these methods are allowed to be used in one model. The package has advanced support for bond graph modeling, making it well known in bond graph communities.


20-sim, Use
For modeling physical systems, the package provides libraries for electrical systems, mechanical systems, hydraulics systems and thermal systems. For block diagrams, libraries comparable to those of Simulink, are provided. A feature of the software is the option to create models with differential equations and package them as block diagram elements or physical components.


20-sim, Use
20-sim models can be simulated using state of the art numerical integration methods. After checking and processing, models are directly converted into machine code, resulting in high speed simulations. Unlike Simulink, simulation results are shown in 20-sim in a separate window called the Simulator. The simulator is versatile: plots can be displayed horizontally and vertically as time and frequency based plots and 3D animations.


20-sim, Use
20-sim is self containing, i.e. no additional software is required and all toolboxes are included. Toolboxes are available for model building, time domain analysis, frequency domain analysis and controller design. To enable scripting it is necessary to install either Matlab, GNU Octave, or Python. The last is included as an optional feature in the 20-sim installer.