title: Infestissumam

text: The album's cover art is part of a single, large piece that was separated into 12 or 13 pictures. These were used as thumbnails for the videos of songs from the album on Ghost's YouTube channel. It was made in collaboration with the band and drawn by Polish artist Zbigniew Bielak and inspired by the album's lyrics and themes. A Nameless Ghoul said that because the album deals with the Antichrist "we knew there was going to be a baby on the front cover. It also represents the paradox of inborn evil, of being very innocent and very vulnerable", and said that it is a pastiche of the film "Amadeus".


title: Infestissumam

text: "Infestissumam" was originally scheduled to be released on April 9, however the band could not find a manufacturer for the CD in the United States and its release was delayed until April 16. A source close to the band told "Spin" that Ghost was turned down by four US CD manufacturers because of artwork of the album's deluxe edition, which is a 16th-century illustration of an orgy. The magazine said it was the depiction of Jesus Christ crucified upside down that caused the controversy instead of the Gustave Doré-inspired work's sexual content. However, a Nameless Ghoul said it was indeed because of the sexual content and said it was ironic that "just because we had naked women as well as female body parts shown and exposed, that caused the problem. What about the blasphemy? What about the Satanism? That wasn't the problem. That's exactly what the record is about." Rather than delay the album longer, the band decided to use the CD artwork from the regular edition for the US pressings on the deluxe edition CD. All European copies and the US vinyl version include the controversial artwork as "Vinyl manufacturers don't have a problem with the artwork. Neither does Europe."


title: Infestissumam

text: On December 14, 2012, the website SecularHaze.com was created by Ghost. The website contained a sound clip of a new Ghost song without vocals. On the page was a clock ticking backwards and five candles, each playing one element of the new song when the user hovered over it with the mouse. The next day, the band uploaded a new song to their official YouTube channel, also called "Secular Haze". Later that day, they performed a special concert in their hometown of Linköping, Sweden, performing the entire "Opus Eponymous" record along with "Secular Haze" and their cover of "I'm a Marionette". Before "Secular Haze" was performed, Papa Emeritus, the band's vocalist, disappeared into the black of the stage to be replaced by Papa Emeritus II. After this concert, SecularHaze.com was updated to include a sixth candle containing the vocal track of the song "Secular Haze". Four days later, the band announced the title of their second album, "Infestissumam", along with the webpage Infestissumam.com which showed the album's track list.


title: Infestissumam

text: "Secular Haze" was the album's first single, given as a free digital download to fans signing up to the band's mailing list from December 15, 2012. A limited pressing of 10" vinyl records of the single was later released. On choosing "Secular Haze" as the first single, a Ghoul said "we wanted to present a song from the new record that sort of stood on its own but without being too far off from the first record". The single's B-side was the cover of ABBA's "I'm a Marionette", which features Dave Grohl of Nirvana and Foo Fighters on drums as well as production. The collaboration happened when, before going to Nashville to record the album, Ghost had a bunch of covers demoed and were discussing if they should squeeze them onto the album. " ... we were at a festival in Europe and Foo Fighters was playing, and we knew that Dave was a fan, and [when we talked to him] after a few handshakes and a few laughs, we were like 'Okay, so you liked the band? So do you want to do something?' And he said yeah, and one month later we were in [his studio in] L.A. doing that." The band recorded their first music video for "Secular Haze" in Linköping, with director Amir Chamdin.


title: Infestissumam

text: On March 12, 2013, Ghost began providing fans with a free streaming of "Year Zero" if they promoted the band on Facebook, by endorsing its frontman to be elected the next Pope of the Catholic Church. The vinyl version of the single includes the B-side "Orez Raey", which is the A-side played backwards. A music video for the song, again directed by Amir Chamdin, was unveiled on March 25. "Loudwire" named it the Best Metal Video of 2013, while "Revolver" named it seventh on their list of the year's best in all genres.


title: Infestissumam

text: The song "Monstrance Clock" was offered for free streaming on April 8. The following day, the entire "Infestissumam" album was uploaded for streaming. While including the songs "La Mantra Mori" and "I'm a Marionette" from the deluxe edition, the Japanese version of the album also features a cover of Depeche Mode's "Waiting for the Night". A third music video, for "Monstrance Clock", was released on July 3, 2013. It was directed by Rob Semmer, filmed at Ghost's shows at the El Rey Theatre and Webster Hall, and opens with footage of fans praising the band in a mock-confessional. In late 2013, Ghost released a special edition of the album, called "Infestissumam Redux". It includes "La Mantra Mori" and the entirety of the "If You Have Ghost" EP, which featured further collaborations with Grohl.


title: Infestissumam

text: "Infestissumam" received generally positive reviews from music critics. At Metacritic, which assigns a normalized rating out of 100 to reviews from mainstream critics, the album received an average score of 67, which indicates "generally favorable reviews," based on 11 reviews. James Christopher Monger of AllMusic described the psychedelic and progressive departures from the band's debut as "weirdly effective" and called the album "a hell of a lot of fun." "The Village Voice" and "Entertainment Weekly" named "Infestissumam" the best metal album of 2013, while "Loudwire" ranked it second on their list. The album was listed by Noisecreep as one of the Best Vinyl Releases of 2013. Both "Secular Haze" and "Year Zero" were named some of the Best Metal Songs of 2013 by "Loudwire". "Infestissumam" won the 2014 Grammis Award for Best Hard Rock/Metal Album. It also won the similar P3 Guld award for Best Rock/Metal Album of the Year.


title: Infestissumam

text: In a less positive review, Jon Hadusek of Consequence of Sound described the album as "pretty tame" and said that "for a band whose songs rely on falsetto and choruses, the absence of memorable melodies on "Infestissumam" is an eternal sin." In Decibel Magazine, Jeff Treppel wrote that Ghost seem to be consciously avoiding a sophomore slump by "throwing together the most eclectic set of songs they could conjure from the pit", and that this "wildly inconsistent ride ... bodes well for the band's longevity."


title: Infestissumam

text: "Infestissumam" debuted at number one on Sweden's Sverigetopplistan chart, selling nearly five times as many copies as the number two album, Wolves by Miss Li. The album was certified gold by the International Federation of the Phonographic Industry in October 2014, for sales of 20,000. "Infestissumam Redux" reached number 8 on the Sverigetopplistan. In the United States, "Infestissumam" sold an estimated 14,000 copies in its first week and debuted at number 28 on the "Billboard" 200 chart. Blabbermouth.net reported that the album had sold nearly 70,000 copies in the US by November 2015.


title: Infestissumam

text: All original songs credited to "A Ghoul Writer" in the booklet; actual writing credits adapted from ASCAP.


title: Just Add Magic (TV series)

text: Just Add Magic is an American live-action family television series, loosely based on the book of the same name by Cindy Callaghan. It was produced by Amazon Studios. A pilot was produced in 2015 and the series commissioned for a full season the following year. Amazon renewed the series for a second season in June 2016 after it "set a record as the most successful Amazon Original Kids premiere weekend in terms of U.S. Prime Video streams and hours."


title: Just Add Magic (TV series)

text: In the town of Saffron Falls, teenage girls Kelly, Darbie, and Hannah are best friends who love baking. They unearth an ancient mysterious cookbook involving magic. The girls visit Mama P's shop to buy magical ingredients, such as "Cedronian vanilla" and "Taurian thyme". The girls use magic at school, and soon realize that they are the protectors of the magical cookbook like many before them, such as Mama P, Ms. Silvers (Neighbor), and Grandma Becky. Kelly has one main goal: to find a magical recipe that will fix her grandmother's curse, Mama P’s curse does not let her leave Saffron Falls, and Ms. Silvers curse does not let her play the piano in public. They attempt to bake a curse-breaking to help the three, except, it also brings back Chuck. .


title: Just Add Magic (TV series)

text: After breaking every curse, they realised that they had brought back Chuck Hankins, a teenage boy from the ’60s who had suddenly disappeared because of The OC's (Original Cooks): were all once the protectors of the cookbook. Chuck casts an invisibility spell but, the girls are able to see and enter the invisible trailer. There they discover that Chuck has another cookbook that is copying recipes from their cookbook, so they steal it. Later the original cooks put a spell on Chuck, and he retaliates with spells of his own. Eventually, they break Chuck's Immortality Spell, also breaking Rose's and frees her from the book. Chuck and Rose go back in time and live out their lives.


title: Just Add Magic (TV series)

text: The book and spices are stolen from Kelly's backpack. Kelly, Hannah, and Darbie meet a previous protector from the '90s named RJ. With Jake's help, they are able to get the book back. The girls become suspicious of Mr.Morris, Hannah's teacher at Fox Canyon for erasing everyone's memories of magic but it wasn't him, it was Caroline, a former protector of the cookbook, who was also disguised as Jill, Mrs. Quinn's campaign manager. The trio take precautionary measures to stop Caroline from casting spells on them and destroying their spices. despite the consequences Cedronian vanilla could bring them.


title: Just Add Magic (TV series)

text: Mama P's has been bought by a coffee chain called Springtown Coffee. Kelly, Hannah, and Darbie become suspicious of the manager Erin Chua. They soon notice clues of someone who knows that magic is real, even after all memories of magic have been erased. This, someone, steals their newly harvested Night Blooming spices, and is therefore dubbed the "Night Bandit." The girls meet Darbie's friend, Piper, and they introduce her to magic. The four of them work together to find the Night Bandit. It turns out that Kelly is actually the Night Bandit and she was poisoned by the spell that brought back the garden in the previous season, Come Back Kombucha Tea. In the final episode, the spell on her is broken, but the girls needed to save Grandma Becky after she disappears. They go back in time and save her, thus also creating a new spice named "Parquinnien" which is a blend of their last names (Hannah Parker-Kent, Kelly Quinn, Darbie O’Brien). The cookbook moves on to Zoe, Erin's daughter and one of the new protectors.


title: Just Add Magic (TV series)

text: The cookbook has moved on to the new protectors: Zoe (Erin's daughter), Ish (Zoe's neighbor) and Leo (Zoe's stepbrother). With the help of Kelly, Darbie, and Hannah, the new trio are convinced that magic exists and able to go through troubling times together.


title: Just Add Magic (TV series)

text: In the spinoff series, new protectors Zoe, Ish, and Leo are set to solve their first mystery. Zoe, wanting to learn more about her father who had died when she was two years old, uncovers a book at the library that had been associated with him. The book tells a story from the late 1800s, narrated from the point of view of Ian Maddox, who was then a protector along with brothers Clint and Folsom Wesson. The Wesson brothers grew power-hungry and created a magical sourdough starter that would help them get large quantities of gold, but the downside of the spell was that it caused mass destruction. With Charles Peizer's assistance, Ian Maddox traveled to the future to hide the starter from the Wesson brothers. Zoe, Ish, and Leo find themselves in a race against the Wessons' descendants to find the sourdough starter. Their goal is to find three coins that will help them discover where the starter is and then destroy it once and for all—if the Wessons don't get to it first. Towards the end, with the help of Kelly, Darbie, and Hannah, the trio is successful in saving the world by using the sourdough starter to distribute the magic from the book throughout the globe.


title: Just Add Magic (TV series)

text: On January 4, 2018, a trailer was released announcing more episodes, which premiered on Amazon on January 19, 2018, as an extension of the second season.


title: Just Add Magic (TV series)

text: On January 11, 2019, a trailer was released announcing the third season, which premiered on February 1.


title: Just Add Magic (TV series)

text: On September 20, 2019, an announcement was made that a "Just Add Magic" special would come out on October 25.


title: Just Add Magic (TV series)

text: Angela Arsenault of Decider.com positively reviewed the first season of the series, calling it "A More Than Worthy Addition To The Teenage Witch Sub-Genre[.]" Jessica Jernigan also gave the second season a positive review, saying that "[d]arkness and danger is leavened with humor. And the supernatural elements are amplifications of real-life situations and experiences. By the season finale, it’s not just magic that saves the day—it’s also humanity." Giving the first season 4/5 stars, Emily Ashby of Common Sense Media noted that


title: Vincent Palermo

text: Vincent "Vinny Ocean" Palermo (born June 4, 1944) is an Italian American former mobster who was "de facto" boss of the New Jersey DeCavalcante crime family before becoming a government witness in 1999. Fictional mob boss Tony Soprano, the protagonist of the HBO series "The Sopranos", is said to be based upon Palermo. He also owned a strip club called Wiggles, which was the inspiration behind the show's Bada Bing! strip club.


title: Vincent Palermo

text: Palermo was raised in a traditional Italian American family in Brooklyn, New York. He was an in-law by marriage to Nicholas Delmore, the former head of the New Jersey crime family whose nephew was Simone DeCavalcante, also a New Jersey mob family leader whose daughter he married. He has five sisters, including Claire and Nancy, and one brother. His father was an Italian immigrant who moved to New York when he was a teenager. Palermo came from a close-knit family, and was said to have lived a harmonious lifestyle. He was an altar boy during adolescence. When Palermo was sixteen, his father died, which forced him to leave school and work two jobs to help support his family, as his mother was a bedridden asthmatic. In his earlier years, Palermo worked at a wholesale fish business in the Fulton Fish Market, where he earned the nickname "Vinny Ocean".


title: Vincent Palermo

text: Palermo was very protective of children; he allegedly once stopped a man from beating his son, and rescued a toddler relative who had accidentally fallen into a pool. Palermo was also reputedly a dedicated family man. He attended Sacred Heart Church in Island Park, New York, drove his daughters to Brownie meetings, and reportedly watched "Annie" with one of his daughters regularly. Palermo also took in a troubled teenager named Richard, becoming his godfather. Palermo would allow his godson to stay at his home every weekend for a year, enabling the boy to study the Catholic sacraments in preparation for eventual baptism, Communion and Confirmation.


title: Vincent Palermo

text: Palermo was divorced once and remarried. In the 1980s, he became indebted to a hospital, local doctors, and the federal government. The tax liens against his property were in his second wife's name, an Italian-American woman named Angela, totaling $68,000. At the time, he was paying a large mortgage on a waterfront mansion with a 100-foot pier located in Island Park. He had two Social Security numbers and paid alimony to his first wife. He also supports his second family, two daughters, Danielle and Tara, and a son Vincent Palermo Jr., with Michael (from his first marriage) and Renee. His son Michael is a graduate of Fordham University and a licensed New York stockbroker; he was an investment banker with Goldman Sachs up until his father's indictment, when Vincent Palermo Jr went into hiding.


title: Vincent Palermo

text: In the early 1960s, Palermo met and married the niece of crime boss Sam DeCavalcante of the DeCavalcante crime family. DeCavalcante took a liking to his nephew-in-law and began inviting him to visit his social club in Kenilworth, New Jersey. He worked at the fish markets in the early morning hours and hung out with mobsters on Sunday afternoons. Palermo cultivated relationships with other crime families—a lucrative loansharking operation with one Gambino family "caporegime" and bookmaking with another. He was also a close associate of the Genovese family. Palermo was known to say very little, speaking to only a very few close associates, and stayed away from mob-run social clubs. Until his racketeering indictment, he had only been arrested for the misdemeanor of stealing shrimp at the Fulton Fish Market.


title: Vincent Palermo

text: On September 11, 1989, Palermo, Anthony Capo, and James "Jimmy" Gallo murdered Staten Island resident Fred Weiss, on orders from DeCavalcante boss Giovanni "John the Eagle" Riggi through capo Anthony Rotondo. Weiss was a former newspaper reporter for the "Staten Island Advance" and a real estate developer who had become associated with mobsters from both the DeCavalcante and Gambino families.


title: Vincent Palermo

text: Weiss and two mob partners had purchased a vacant property in Staten Island and started illegally dumping large amounts of dangerous medical waste there. Local authorities uncovered the scheme and started investigating Weiss, and the two mob families became nervous. Gambino boss John Gotti worried that Weiss might become a government witness in exchange for leniency and requested that the DeCavalcante family murder Weiss to protect them. Palermo, Capo, and Gallo drove to the New York condominium of Weiss' girlfriend. As Weiss left the building and climbed into his car, Palermo and Gallo shot him in the face.


title: Vincent Palermo

text: Palermo was appointed capo after the Weiss murder and given his own crew of soldiers. Riggi was sent to prison in 1989, and appointed John "Johnny Boy" D'Amato as his acting boss. In January 1992, Anthony Capo participated in the murder of acting boss D'Amato. Earlier in 1991, D'Amato's girlfriend, retaliating against D'Amato over an argument, told Anthony Rotondo that D'Amato was an active bisexual. She described swinging encounters that D'Amato had in Manhattan sex clubs with both women and men. Rotondo shared this information with underboss Giacomo Amari, and consigliere Stefano Vitabile. In 2003, capos Philip "Phil" Abramo, Giuseppe "Pino" Schifilliti and the reputed consigliere Stefano Vitabile were charged in organizing various crimes, including the murder of D'Amato. Reputed men involved in the murder conspiracy, Palermo, Capo and Rotondo would later testify about this murder against their former associates.


title: Vincent Palermo

text: With Amari's death, there was no clear candidate to become the new acting boss. Riggi, still in prison, restructured the family and created a ruling panel to run it in order to avoid a potential power struggle. Riggi appointed longtime members of the crime family to the panel: Vincent Palermo, Girolamo "Jimmy" Palermo (no relation to Vincent), and Charles Majuri. However, Majuri, furious that he wasn't appointed acting boss, decided to murder the two Palermos and take effective control of the DeCavalcante family. He asked Gallo to murder Vincent Palermo, but Gallo alerted Palermo about the plot.


title: Vincent Palermo

text: To protect himself, Palermo decided to murder Majuri instead. Over the years, Majuri had made many enemies by removing fellow mobsters from a labor union that he controlled and taking their money. Palermo was able to recruit Capo, Gallo, and Joseph Masella to find and kill Majuri. However, on the one occasion when they were ready to kill Majuri, they became nervous and decided not to do it. When they reported their failure back to Palermo, he decided that Majuri didn't pose a threat after all and cancelled the murder contract. By the mid-90s, Palermo was the "de facto" boss of the DeCavalcante family, with Riggi reigning as boss "in absentia" from jail.


title: Vincent Palermo

text: In 1998, DeCavalcante associate Ralph Guarino was arrested for stealing $1.6 million dollars from a Bank of America inside the World Trade Center. To avoid 20 years in prison, Guarino agreed to work as an informant for the FBI, giving the agency information on the actions of DeCavalcante members. The agency gave him cell phones rigged with surveillance equipment to distribute to other family members. In October 1998, Palermo's trusted lieutenant Joseph Masella was shot to death, leaving an opening in the family. Guarino's status had been rising in the family due to secret assistance from the FBI, and after Masella's murder, Palermo and the rest of the DeCavalcante leadership promoted Guarino to made man.


title: Vincent Palermo

text: In 1999, Palermo faced charges and possible capital offenses, so he decided to become a government witness. He confessed to killing Weiss and mobster Louis LaRasso, and to planning the murders of the two D'Amatos, Masella, Majuri, and Tom Salvata, the manager at his strip club. Palermo also implicated other DeCavalcante family members in various crimes. After testifying for the government, Palermo and his family entered the federal Witness Protection Program. However, prosecutors later discovered that he allegedly gave his son Michael $1 million in cash, possibly jeopardizing his status as a protected witness.


title: Vincent Palermo

text: On September 14, 2009, the "New York Daily News" exposed Palermo's new life in witness protection as a strip club operator in Houston, Texas. He has been living under the name "James Cabella". Houston Police alleged that Palermo's strip clubs were a source of drug dealing and prostitution in the Houston area. Palermo claimed that many of his Houston friends already knew of his past because of an A&E television special. He lived in a gated mansion in Houston.


title: Vincent Palermo

text: The day after the "Daily News" report, Houston NBC affiliate KPRC-TV aired an investigative segment on Palermo. Forty days later, Palermo put his Houston mansion up for sale, first for $4 million but then, over the following two years, he reduced the price to $2.45 million. After the mansion still would not sell, he took it off the market on June 3, 2011. Palermo put his house up for sale again in September 2015; it eventually sold for $2.85 million on 5 August 2016. In late 2011, the "Houston Chronicle" reported that Palermo was sued by the former owner of one of his strip clubs, claiming that he had only paid $5,000 of the $1.3 million selling price.


title: Vincent Palermo

text: On March 4, 2013, Palermo filed a Chapter 11 bankruptcy petition in U.S. Bankruptcy Court in the Southern District of Texas. Under Chapter 11, a person's assets and debts are not liquidated, but the filer is given court protection from creditors in order to try to perform a work-out of the insolvency situation.


title: Nuclear force

text: The nuclear force (or nucleon–nucleon interaction, residual strong force, or, historically, strong nuclear force) is a force that acts between the protons and neutrons of atoms. Neutrons and protons, both nucleons, are affected by the nuclear force almost identically. Since protons have charge +1 "e", they experience an electric force that tends to push them apart, but at short range the attractive nuclear force is strong enough to overcome the electromagnetic force. The nuclear force binds nucleons into atomic nuclei.


title: Nuclear force

text: The nuclear force is powerfully attractive between nucleons at distances of about 0.8 femtometre (fm, or 0.8×10 metre), but it rapidly decreases to insignificance at distances beyond about 2.5 fm. At distances less than 0.7 fm, the nuclear force becomes repulsive. This repulsion is responsible for the size of nuclei, since nucleons can come no closer than the force allows. (The size of an atom, measured in angstroms (Å, or 10 m), is five orders of magnitude larger). The nuclear force is not simple, though, as it depends on the nucleon spins, has a tensor component, and may depend on the relative momentum of the nucleons.


title: Nuclear force

text: The nuclear force has an essential role in storing energy that is used in nuclear power and nuclear weapons. Work (energy) is required to bring charged protons together against their electric repulsion. This energy is stored when the protons and neutrons are bound together by the nuclear force to form a nucleus. The mass of a nucleus is less than the sum total of the individual masses of the protons and neutrons. The difference in masses is known as the mass defect, which can be expressed as an energy equivalent. Energy is released when a heavy nucleus breaks apart into two or more lighter nuclei. This energy is the electromagnetic potential energy that is released when the nuclear force no longer holds the charged nuclear fragments together.


title: Nuclear force

text: A quantitative description of the nuclear force relies on equations that are partly empirical. These equations model the internucleon potential energies, or potentials. (Generally, forces within a system of particles can be more simply modeled by describing the system's potential energy; the negative gradient of a potential is equal to the vector force.) The constants for the equations are phenomenological, that is, determined by fitting the equations to experimental data. The internucleon potentials attempt to describe the properties of nucleon–nucleon interaction. Once determined, any given potential can be used in, e.g., the Schrödinger equation to determine the quantum mechanical properties of the nucleon system.


title: Nuclear force

text: The discovery of the neutron in 1932 revealed that atomic nuclei were made of protons and neutrons, held together by an attractive force. By 1935 the nuclear force was conceived to be transmitted by particles called mesons. This theoretical development included a description of the Yukawa potential, an early example of a nuclear potential. Pions, fulfilling the prediction, were discovered experimentally in 1947. By the 1970s, the quark model had been developed, by which the mesons and nucleons were viewed as composed of quarks and gluons. By this new model, the nuclear force, resulting from the exchange of mesons between neighboring nucleons, is a residual effect of the strong force.


title: Nuclear force

text: While the nuclear force is usually associated with nucleons, more generally this force is felt between hadrons, or particles composed of quarks. At small separations between nucleons (less than ~ 0.7 fm between their centers, depending upon spin alignment) the force becomes repulsive, which keeps the nucleons at a certain average separation. For identical nucleons (such as two neutrons or two protons) this repulsion arises from the Pauli exclusion force. A Pauli repulsion also occurs between quarks of the same flavour from different nucleons (a proton and a neutron).


title: Nuclear force

text: At distances larger than 0.7 fm the force becomes attractive between spin-aligned nucleons, becoming maximal at a center–center distance of about 0.9 fm. Beyond this distance the force drops exponentially, until beyond about 2.0 fm separation, the force is negligible. Nucleons have a radius of about 0.8 fm.


title: Nuclear force

text: At short distances (less than 1.7 fm or so), the attractive nuclear force is stronger than the repulsive Coulomb force between protons; it thus overcomes the repulsion of protons within the nucleus. However, the Coulomb force between protons has a much greater range as it varies as the inverse square of the charge separation, and Coulomb repulsion thus becomes the only significant force between protons when their separation exceeds about 2 to 2.5 fm.


title: Nuclear force

text: The nuclear force has a spin-dependent component. The force is stronger for particles with their spins aligned than for those with their spins anti-aligned. If two particles are the same, such as two neutrons or two protons, the force is not enough to bind the particles, since the spin vectors of two particles of the same type must point in opposite directions when the particles are near each other and are (save for spin) in the same quantum state. This requirement for fermions stems from the Pauli exclusion principle. For fermion particles of different types, such as a proton and neutron, particles may be close to each other and have aligned spins without violating the Pauli exclusion principle, and the nuclear force may bind them (in this case, into a deuteron), since the nuclear force is much stronger for spin-aligned particles. But if the particles' spins are anti-aligned the nuclear force is too weak to bind them, even if they are of different types.


title: Nuclear force

text: The nuclear force also has a tensor component which depends on the interaction between the nucleon spins and the angular momentum of the nucleons, leading to deformation from a simple spherical shape.


title: Nuclear force

text: To disassemble a nucleus into unbound protons and neutrons requires work against the nuclear force. Conversely, energy is released when a nucleus is created from free nucleons or other nuclei: the nuclear binding energy. Because of mass–energy equivalence (i.e. Einstein's formula ), releasing this energy causes the mass of the nucleus to be lower than the total mass of the individual nucleons, leading to the so-called "mass defect".


title: Nuclear force

text: The nuclear force is nearly independent of whether the nucleons are neutrons or protons. This property is called "charge independence". The force depends on whether the spins of the nucleons are parallel or antiparallel, as it has a non-central or "tensor" component. This part of the force does not conserve orbital angular momentum, which under the action of central forces is conserved.


title: Nuclear force

text: The symmetry resulting in the strong force, proposed by Werner Heisenberg, is that protons and neutrons are identical in every respect, other than their charge. This is not completely true, because neutrons are a tiny bit heavier, but it is an approximate symmetry. Protons and neutrons are therefore viewed as the same particle, but with different isospin quantum numbers; conventionally, the proton is "isospin up," while the neutron is "isospin down". The strong force is invariant under SU(2) isospin transformations, just as other interactions between particles are invariant under SU(2) transformations of intrinsic spin. In other words, both isospin and intrinsic spin transformations are isomorphic to the SU(2) symmetry group. There are only strong attractions when the total isospin of the set of interacting particles is 0, which is confirmed by experiment.


title: Nuclear force

text: Our understanding of the nuclear force is obtained by scattering experiments and the binding energy of light nuclei.


title: Nuclear force

text: The nuclear force is distinct from what historically was known as the weak nuclear force. The weak interaction is one of the four fundamental interactions, and plays a role in processes such as beta decay. The weak force plays no role in the interaction of nucleons, though it is responsible for the decay of neutrons to protons and vice versa.


title: Nuclear force

text: The nuclear force has been at the heart of nuclear physics ever since the field was born in 1932 with the discovery of the neutron by James Chadwick. The traditional goal of nuclear physics is to understand the properties of atomic nuclei in terms of the "bare" interaction between pairs of nucleons, or nucleon–nucleon forces (NN forces).


title: Nuclear force

text: Within months after the discovery of the neutron, Werner Heisenberg and Dmitri Ivanenko had proposed proton–neutron models for the nucleus. Heisenberg approached the description of protons and neutrons in the nucleus through quantum mechanics, an approach that was not at all obvious at the time. Heisenberg's theory for protons and neutrons in the nucleus was a "major step toward understanding the nucleus as a quantum mechanical system". Heisenberg introduced the first theory of nuclear exchange forces that bind the nucleons. He considered protons and neutrons to be different quantum states of the same particle, i.e., nucleons distinguished by the value of their nuclear isospin quantum numbers.


title: Nuclear force

text: One of the earliest models for the nucleus was the liquid-drop model developed in the 1930s. One property of nuclei is that the average binding energy per nucleon is approximately the same for all stable nuclei, which is similar to a liquid drop. The liquid-drop model treated the nucleus as a drop of incompressible nuclear fluid, with nucleons behaving like molecules in a liquid. The model was first proposed by George Gamow and then developed by Niels Bohr, Werner Heisenberg, and Carl Friedrich von Weizsäcker. This crude model did not explain all the properties of the nucleus, but it did explain the spherical shape of most nuclei. The model also gave good predictions for the binding energy of nuclei.


title: Nuclear force

text: In 1934, Hideki Yukawa made the earliest attempt to explain the nature of the nuclear force. According to his theory, massive bosons (mesons) mediate the interaction between two nucleons. In light of quantum chromodynamics (QCD)—and, by extension, the Standard Model—meson theory is no longer perceived as fundamental. But the meson-exchange concept (where hadrons are treated as elementary particles) continues to represent the best working model for a quantitative "NN" potential. The Yukawa potential (also called a screened Coulomb potential) is a potential of the form


title: Nuclear force

text: where "g" is a magnitude scaling constant, i.e., the amplitude of potential, formula_2 is the Yukawa particle mass, "r" is the radial distance to the particle. The potential is monotone increasing, implying that the force is always attractive. The constants are determined empirically. The Yukawa potential depends only on the distance "r" between particles, hence it models a central force.


title: Nuclear force

text: Throughout the 1930s a group at Columbia University led by I. I. Rabi developed magnetic-resonance techniques to determine the magnetic moments of nuclei. These measurements led to the discovery in 1939 that the deuteron also possessed an electric quadrupole moment. This electrical property of the deuteron had been interfering with the measurements by the Rabi group. The deuteron, composed of a proton and a neutron, is one of the simplest nuclear systems. The discovery meant that the physical shape of the deuteron was not symmetric, which provided valuable insight into the nature of the nuclear force binding nucleons. In particular, the result showed that the nuclear force was not a central force, but had a tensor character. Hans Bethe identified the discovery of the deuteron's quadrupole moment as one of the important events during the formative years of nuclear physics.


title: Nuclear force

text: Historically, the task of describing the nuclear force phenomenologically was formidable. The first semi-empirical quantitative models came in the mid-1950s, such as the Woods–Saxon potential (1954). There was substantial progress in experiment and theory related to the nuclear force in the 1960s and 1970s. One influential model was the Reid potential (1968)


title: Nuclear force

text: where formula_4 and where the potential is given in units of MeV. In recent years, experimenters have concentrated on the subtleties of the nuclear force, such as its charge dependence, the precise value of the π"NN" coupling constant, improved phase-shift analysis, high-precision "NN" data, high-precision "NN" potentials, "NN" scattering at intermediate and high energies, and attempts to derive the nuclear force from QCD.


title: Nuclear force

text: The nuclear force is a residual effect of the more fundamental strong force, or strong interaction. The strong interaction is the attractive force that binds the elementary particles called quarks together to form the nucleons (protons and neutrons) themselves. This more powerful force, one of the fundamental forces of nature, is mediated by particles called gluons. Gluons hold quarks together through color charge which is analogous to electric charge, but far stronger. Quarks, gluons, and their dynamics are mostly confined within nucleons, but residual influences extend slightly beyond nucleon boundaries to give rise to the nuclear force.


title: Nuclear force

text: The nuclear forces arising between nucleons are analogous to the forces in chemistry between neutral atoms or molecules called London dispersion forces. Such forces between atoms are much weaker than the attractive electrical forces that hold the atoms themselves together (i.e., that bind electrons to the nucleus), and their range between atoms is shorter, because they arise from small separation of charges inside the neutral atom. Similarly, even though nucleons are made of quarks in combinations which cancel most gluon forces (they are "color neutral"), some combinations of quarks and gluons nevertheless leak away from nucleons, in the form of short-range nuclear force fields that extend from one nucleon to another nearby nucleon. These nuclear forces are very weak compared to direct gluon forces ("color forces" or strong forces) inside nucleons, and the nuclear forces extend only over a few nuclear diameters, falling exponentially with distance. Nevertheless, they are strong enough to bind neutrons and protons over short distances, and overcome the electrical repulsion between protons in the nucleus.


title: Nuclear force

text: Sometimes, the nuclear force is called the residual strong force, in contrast to the strong interactions which arise from QCD. This phrasing arose during the 1970s when QCD was being established. Before that time, the "strong nuclear force" referred to the inter-nucleon potential. After the verification of the quark model, "strong interaction" has come to mean QCD.


title: Nuclear force

text: Two-nucleon systems such as the deuteron, the nucleus of a deuterium atom, as well as proton–proton or neutron–proton scattering are ideal for studying the "NN" force. Such systems can be described by attributing a "potential" (such as the Yukawa potential) to the nucleons and using the potentials in a Schrödinger equation. The form of the potential is derived phenomenologically (by measurement), although for the long-range interaction, meson-exchange theories help to construct the potential. The parameters of the potential are determined by fitting to experimental data such as the deuteron binding energy or "NN" elastic scattering cross sections (or, equivalently in this context, so-called "NN" phase shifts).


title: Nuclear force

text: The most widely used "NN" potentials are the Paris potential, the Argonne AV18 potential, the CD-Bonn potential, and the Nijmegen potentials.


title: Nuclear force

text: A more recent approach is to develop effective field theories for a consistent description of nucleon–nucleon and three-nucleon forces. Quantum hadrodynamics is an effective field theory of the nuclear force, comparable to QCD for color interactions and QED for electromagnetic interactions. Additionally, chiral symmetry breaking can be analyzed in terms of an effective field theory (called chiral perturbation theory) which allows perturbative calculations of the interactions between nucleons with pions as exchange particles.


title: Nuclear force

text: The ultimate goal of nuclear physics would be to describe all nuclear interactions from the basic interactions between nucleons. This is called the "microscopic" or "ab initio" approach of nuclear physics. There are two major obstacles to overcome:


title: Nuclear force

text: This is an active area of research with ongoing advances in computational techniques leading to better first-principles calculations of the nuclear shell structure. Two- and three-nucleon potentials have been implemented for nuclides up to "A" = 12.


title: Nuclear force

text: A successful way of describing nuclear interactions is to construct one potential for the whole nucleus instead of considering all its nucleon components. This is called the "macroscopic" approach. For example, scattering of neutrons from nuclei can be described by considering a plane wave in the potential of the nucleus, which comprises a real part and an imaginary part. This model is often called the optical model since it resembles the case of light scattered by an opaque glass sphere.


title: Nuclear force

text: Nuclear potentials can be "local" or "global": local potentials are limited to a narrow energy range and/or a narrow nuclear mass range, while global potentials, which have more parameters and are usually less accurate, are functions of the energy and the nuclear mass and can therefore be used in a wider range of applications.


title: Super Metroid

text: Following the established gameplay model of its predecessors, "Super Metroid" focuses on exploration, with the player searching for power-ups used to reach previously inaccessible areas. It introduced new concepts to the series, such as the inventory screen, an automap, and the ability to fire in all directions. The development staff from previous "Metroid" games—including Yoshio Sakamoto, Makoto Kano and Gunpei Yokoi—returned to develop "Super Metroid" over the course of two years. The developers wanted to make a true action game, and set the stage for Samus's reappearance.


title: Super Metroid

text: "Super Metroid" received acclaim, with praise for its atmosphere, gameplay, music and graphics. It is often cited as one of the greatest video games of all time. The game sold well and shipped 1.42 million copies worldwide by late 2003. Alongside "", "Super Metroid" is credited for establishing the "Metroidvania" genre, inspiring numerous indie games and developers. It also became popular among players for speedrunning. "Super Metroid" was followed in 2002 by "Metroid Fusion" and "Metroid Prime". It has been rereleased on several Nintendo consoles and services.


title: Super Metroid

text: "Super Metroid" is a 2D side-scrolling action-adventure game, which primarily takes place on the fictional planet Zebes from the original game—a large, open-ended world with areas connected by doors and elevators. The player controls Samus Aran as she searches the planet for a Metroid that has been stolen by Ridley, the leader of the Space Pirates. Samus can run, jump, crouch, and fire a weapon in eight directions; she can also perform other actions, such as wall jumping—jumping from one wall to another in rapid succession to reach higher areas. The "Moon Walk" ability, named after the popular dance move of the same name, allows Samus to walk backwards while firing or charging her weapon.


title: Super Metroid

text: Throughout the course of the game, the player can acquire power-ups that enhance Samus's armor and weaponry, as well as grant her special abilities, allowing them to gain access to areas that were previously inaccessible. The Morphing Ball allows Samus to curl into a ball and roll into tight places; while in this form, she can plant bombs once a Bomb power-up is acquired. The Spring Ball adds the ability to jump while in Morphing Ball form. The Speed Booster can be used to run at high speeds and crash into barriers and enemies. The Hi-Jump Boots allow for a higher jump, and the Space Jump allows Samus to jump in midair. The Grapple Beam can be used to swing across open areas. The X-ray Scope is used to see items and passages through hidden walls and other surfaces.


title: Super Metroid

text: The heads-up display shows Samus's health, the supply mode for Reserve Tanks, icons that represent weapons, and a map display showing her location and its surroundings. The inventory screen allows the player to enable and disable weapons and abilities. While the beam weapons can be combined, the Spazer and Plasma beams cannot be used simultaneously. At the game's end, Samus obtains the Hyper Beam, a powerful weapon generated by the energy given to her by the "super Metroid", the matured version of the larval creature that she seeks over the course of the game. The backup units called Reserve Tanks can be used automatically when Samus's health is depleted. The game also features an automap to help players navigate the different areas of the game. Additionally, the player can use the map computer found in each part of the planet to reveal unexplored areas. To save their progress, the player must find and use one of the save stations scattered around the planet. The game can also be saved at Samus's gunship, which fully recharges her health and ammunition as well. "Super Metroid" has three endings based on the time taken to complete the game, which determine whether Samus poses with or without her suit. The best ending is achieved when the game is completed under three hours. Additionally, an optional task alters the game's end slightly. If the player chooses to rescue the Dachora and the Etecoons, friendly creatures encountered by Samus in the game, they are shown leaving the planet in the distance.


title: Super Metroid

text: Samus Aran brings the last Metroid to the Ceres space colony for scientific study. Investigation of the specimen, a larva, reveals that its energy-producing abilities could actually be harnessed for the good of civilization. Shortly after leaving, Samus receives a distress call alerting her to return to the colony immediately. She finds the scientists dead, and the Metroid larva stolen by Ridley, leader of the Space Pirates. Samus escapes from the colony during a self-destruct sequence and follows Ridley to the planet Zebes. She searches the planet for the Metroid and finds that the Pirates have rebuilt their base there.


title: Super Metroid

text: After defeating four bosses including Ridley in various regions of Zebes, Samus enters Tourian, the heart of the Pirates' base, and fights several Metroids that have somehow reproduced. A single Metroid that has grown to enormous size attacks and nearly destroys Samus, but relents at the last moment. It is the larva that was stolen from Ceres; because Samus was present at its birth on SR388, the Metroid has imprinted on Samus, recognizing her as its "mother".


title: Super Metroid

text: Samus fights Mother Brain, a biomechanical creature that controls the Zebes systems. Mother Brain overpowers Samus and again she is nearly killed, but the Metroid larva intervenes, attacking Mother Brain and healing Samus, confirming the scientists' findings. Mother Brain kills the Metroid, but upon death, it gives Samus the Hyper Beam, a powerful weapon strong enough to kill Mother Brain. Samus escapes Zebes as it self-destructs.


title: Super Metroid

text: "Super Metroid" was developed by Nintendo R&D1 with a staff of 15 managed by Gunpei Yokoi. It was written and directed by Yoshio Sakamoto, and produced by Makoto Kano. Intelligent Systems, who co-developed the original "Metroid" with R&D1, handled the programming. The opening was narrated by Dan Owsen, a Nintendo of America employee.


title: Super Metroid

text: "Super Metroid" was released almost a decade after the original "Metroid." Sakamoto said: "We wanted to wait until a "true" action game was needed. [...] And also to set the stage for the reappearance of Samus Aran.""" It took half a year for Nintendo to approve the project, and two further years to develop.


title: Super Metroid

text: The developers' primary goal was to make a "good action game". It is the first "Metroid" game to let Samus fire in all directions while moving. It is also among the first open-world games with a map feature, which shows the outlines of rooms and indicates important locations and items. The team wanted to create a large map, but found it difficult to organize the amount of graphic data involved, and so broke it into smaller parts. Areas from previous "Metroid" games were included to create a sense of familiarity.


title: Super Metroid

text: Shortly before the game's release, the North American Entertainment Software Rating Board, a self-regulating organization, was formed in response to the increasing violence in games such as "Mortal Kombat" (1992). Asked whether he thought the controversy would cause a backlash for "Super Metroid", Sakamoto explained that Samus's purpose is to maintain peace in the galaxy, saying: "It's not violence for the sake of violence." The game was demonstrated at the Winter 1994 Consumer Electronics Show, and was named the best Super NES game at the show by "GamePro".


title: Super Metroid

text: The music for "Super Metroid" was composed by Kenji Yamamoto and Minako Hamano, and uses 16-bit versions of music from previous games. The Super NES's sound hardware allowed the playback of samples simultaneously on eight channels, as opposed to three PSG channels and one noise channel of the NES. Yamamoto decided that rich and expressive sounds, such as a female chorus, would be required to portray the setting realistically. He composed the main theme by humming while riding his motorcycle from work.


title: Super Metroid

text: Yamamoto also served as a sound programmer, and wrote a program that sends sound data to the audio chip. He also created sound effects, including those created for an infant Metroid to convey different emotions. The simultaneous roles as a composer, a sound programmer and a sound effect creator gave Yamamoto ideas to produce a distinct "Metroid" soundtrack "with a sound programmer's ear, with a sound effect creator's ear, and with the approach methodology and theory of a composer." The arrangements and remixes of the game's themes were used in "Metroid Prime" and its sequels, because Yamamoto wanted to satisfy old "Metroid" fans, describing it as a "present" for them.


title: Super Metroid

text: A soundtrack album, "Super Metroid: Sound in Action", was published by Sony Records on June 22, 1994. It contains 38 tracks and has a running time of 58:49. It includes the original "Metroid" soundtrack by Hirokazu Tanaka, and additional tracks arranged by Yoshiyuki Ito and Masumi Ito.


title: Super Metroid

text: The game was released by Nintendo in Japan on March 19, 1994, in North America on April 18, and in Europe on July 28. It was distributed on a 24-megabit cartridge. It was re-released through the Nintendo Power service in Japan on September 30, 1997. "Super Metroid" became available as a Wii Virtual Console game in North America on August 20, 2007, in Japan on September 20, and in Europe on October 12. In "Super Smash Bros. Brawl", it is also one of the trial games available in the "Masterpieces" section, which uses Virtual Console technology to emulate older hardware and have time constraints. The game was later released on the Wii U Virtual Console in May 2013, initially available during the trial campaign for a cheaper price before reverting to its regular price the next month. The New Nintendo 3DS-specific Virtual Console also received the release in April 2016. In September 2017, Nintendo released the Super NES Classic Edition, which included "Super Metroid" among its games. "Super Metroid" and other Super NES games were added to the Nintendo Switch Online subscription service in September 2019.


title: Super Metroid

text: "Super Metroid" was met with critical acclaim. Chris Slate of the "Game Players" video game magazine thoroughly enjoyed "Super Metroid", claiming that it "easily lives up to everyone's high expectations". He was satisfied with how Nintendo mixed complex gameplay with "state-of-the-art" graphics and sound. Slate found the newly added auto-mapping feature something that players really needed, saying that it was the only feature in "Super Metroid" that the original "Metroid" should have had. Concluding his review, Slate stated, "Action fans can't afford to miss "Super Metroid". [...] You'll want to play through again and again even after you've beaten it." "Nintendo Power" mentioned that the game "may well be the best action adventure game ever", calling it the "wave of the future". They praised the game's graphics, sound, and controls, while their only negative comment was, "Even 100 megabits of "Metroid" wouldn't be enough." "Electronic Gaming Monthly" gave "Super Metroid" their "Game of the Month" award, comparing it favorably to the original "Metroid" and applauding the graphics, the many weapons and items available, and the music. Each of the four reviewers gave it scores of nine out of ten. "GamePro" criticized that the controls are often awkward or difficult and that many of the power-ups are either lifted from other Super NES games or simple upgrades of other power-ups in the game, but praised the game's massive size along with the auto-mapping feature, saying it "makes a potentially frustrating game accessible to a far wider audience." Andy Robinson of GamesRadar was pleased with the game's "phenomenal" soundtrack, complimenting it as "one of the best videogame scores of all time".


title: Super Metroid

text: "Super Play" critic Zy Nicholson said that "Super Metroid" was better than his favorite game, "Mega Man X", describing it as "more of an experience than a game". Comparing the game to the 1986 film "Aliens", Nicholson felt that the game was best experienced in the dark with the volume turned up. He found the game so compulsive that he was tempted to play "without eating or sleeping". "Super Play" critic Tony Mott cited the atmosphere as its best aspect, and described the game as a mixture of "Aliens", "Turrican" (1990), "Exile" (1989), and "Nodes of Yesod" (1985). Appreciating the game's controls, Mott applauded the refined gameplay. He concluded his review by calling "Super Metroid" "undoubtedly the best game I've played this year so far", predicting that anyone who plays the game would be "playing a game destined for classic status". The third reviewer, James Leach, agreed with Nicholson and Mott that "Super Metroid" was what "Mega Man X" should have been. Concluding his review, Leach wrote that "Super Metroid" contained everything he looked for in a video game: "playability, hidden tricks, powerful weapons and steamingly evil baddies". "Super Play's" verdict was, "We all love this game. "Super Metroid" is absolutely marvelous and "you" should own it."


title: Super Metroid

text: "Edge" criticized the graphics and short length, but praised "Super Metroid" as "intensely playable" and "full of memorable moments". "IGN" called "Super Metroid"s Virtual Console version a "must-own", commenting that although the game was released nine months after the Wii launched, they felt that it was worth the wait. For players who have never played "Super Metroid", IGN claims that they owe themselves as gamers to "finally find out about what you've been missing all these years". In his review for GameSpot, Frank Provo found it "absolutely astonishing that Nintendo let 13 years go by before making "Super Metroid" readily available again", but considered the most important thing was that players "can now play this masterpiece without having to track down the original Super Nintendo Entertainment System cartridge or fumble with legally questionable emulators". Despite admitting that the Virtual Console version was essentially "nothing more than a no-frills, emulated version of a 13-year-old SNES game" that was no longer cutting-edge, he was still pleased with it and reiterated his belief that "Super Metroid" is "one of the best 2D action adventure games ever produced".


title: Super Metroid

text: In Japan, "Super Metroid" was the ninth-best-selling video game of 1994, with 531,000 copies sold that year. In North America, despite receiving critical acclaim, Rus McLaughlin of IGN said that the "Metroid" series "still fell down on the timing, arriving too late in the SNES lifecycle to earn big sales." Robinson similarly noted that, in a series tradition, the game was released "at the wrong place, at the wrong time." With the help of strong marketing from Nintendo, "Super Metroid" sold well in North America, topping the Super NES sales chart in May 1994. A year after its release, Nintendo placed it on their Player's Choice marketing label. By late 2003, the game had shipped 1.42 million copies worldwide.


title: Super Metroid

text: "Super Metroid" received several awards and honors. "Electronic Gaming Monthly" named "Super Metroid" a Game of the Month for May 1994, gave it an Editors' Choice award, awarded it as the Best Action Game of 1994, and named it the best game of all time in 2003. IGN ranked "Super Metroid" 3rd (2003), 10th (2005) and 7th (2007) in its top 100 games of all time lists. Likewise, IGN readers ranked the game 11th in its top 99 games of all-time list in 2005, and 4th in its top 100 games in 2006. Richard George of IGN also ranked "Super Metroid" 3rd in its top 100 SNES games, crediting its "flawless action, impeccable level design, out-of-this-world atmosphere, a totally badass heroine and an enormous overworld to explore." GamesRadar named "Super Metroid" the best SNES game of all time, while "Nintendo Power" named it the best game in the "Metroid" series, beating out "Metroid Prime" and "". "GamePro" listed "Super Metroid" as one of the fifteen must-play retro games on the Wii. Game Informer placed the game 29th on their top 100 games of all time in 2001. In 2018, Complex listed the game 3rd on their "The Best Super Nintendo Games of All Time." They opined that Super Metroid is "tour de force from Nintendo" and described the gameplay as perfect. In 1995, Total! rated the game 17th on its "Top 100 SNES Games." In 1995, Flux magazine listed Super Metroid 62nd in their Top 100 Video Games. They praised the game for its challenging gameplay and haunting atmosphere, although they felt that it is too similar to its predecessor.


title: Super Metroid

text: "Super Metroid" is often regarded as one of the greatest video games of all time. Jeremy Parish of USgamer remarked that "Super Metroid" is a "kind of game you can return to time and again and always come away with some fresh insight or observation." Andrew Webster of "Ars Technica" found the game's atmosphere impressive, and noted that the developers had perfected the aspect on solitude, a concept introduced in the first "Metroid" game. "Game Informer" writer Joe Juba cited the game's ending as "one of the most memorable and empowering moments in gaming history." In 2009, "Official Nintendo Magazine" called the game "Challenging, deep and undeniably epic", placing it 24th on a list of the greatest Nintendo games.


title: Super Metroid

text: As "Super Metroid" gave players awards based on how quick it took them to complete the game, it has become a popular choice for speedrunning, a style of play in which the player intends to complete the game as quickly as possible for the purpose of competition. "Super Metroid", alongside Konami's 1997 game "", is also credited for establishing the "Metroidvania" genre. It was cited as an influence on other Metroidvania games, including "Shadow Complex" and "Axiom Verge".


title: Super Metroid

text: Several ROM hacks for "Super Metroid" were released by fans, which added new features that are not included in the original game. "Super Metroid: Redesign", created by "drewseph" in 2006, features new items, expanded areas and modified physics. In 2011, a Japanese hacker named "SB" released a ROM hack titled "Metroid: Super Zero Mission", which intends to combine elements from "Super Metroid" and "".


title: Super Metroid

text: Nintendo did not release another "Metroid" game for eight years, as the series did not match the success of the "Mario" and "Legend of Zelda" franchises. Yokoi left Nintendo in August 1996, amid the failure of the Virtual Boy, and died in a car accident in October 1997.


title: Super Metroid

text: Fans eagerly awaited a "Metroid" game for the Nintendo 64 (N64). According to Nintendo producer Shigeru Miyamoto, Nintendo did not develop a "Metroid" game for the N64 as they "couldn't come out with any concrete ideas". Sakamoto said he could not imagine how the N64 controller could be used to control Samus. Nintendo approached another company to make an N64 "Metroid", but the offer was declined because the developers thought they could not make a game to equal "Super Metroid".


title: Super Metroid

text: In late 2002, Nintendo released "Metroid Fusion," a 2D game developed for the Game Boy Advance by Nintendo R&D1, and "Metroid Prime", a first-person game developed for the GameCube by the American company Retro Studios, and the first "Metroid" game to use 3D graphics. Both "Fusion" and "Prime" garnered acclaim, with "Prime" winning several Game of the Year awards. After "Metroid Prime", three more games in the first-person perspective and a pinball spin-off were released, including its sequel, "" (2004).


title: Ronald Lauder

text: Ronald (Ron) Steven Lauder (born February 26, 1944) is an American businessman, billionaire, philanthropist, art collector, and political activist. He is the president of the World Jewish Congress since 2007. He and his brother, Leonard Lauder, are the sole heirs to the Estée Lauder cosmetics company, founded by their parents, Estée Lauder and Joseph Lauder, in 1946. According to "Forbes", Lauder has a net worth of $4.5 billion dollars as of Sept. 2022 (number 563 on Forbes' list of billionaires)


title: Ronald Lauder

text: Lauder was born in New York City to a Jewish family, the son of Estée Lauder and Joseph Lauder, founders of Estée Lauder Companies. He is the younger brother of Leonard Lauder, chairman of the board of the Estée Lauder Companies.


title: Ronald Lauder

text: He attended the Bronx High School of Science and holds a bachelor's degree in International Business from the Wharton School of Business at the University of Pennsylvania. He studied at the University of Paris, and received a Certificate in International Business from the University of Brussels.


title: Ronald Lauder

text: Lauder started to work for the Estée Lauder Company in 1964 as head of the international department. In 1984, he became a Deputy Assistant Secretary of Defense for European and NATO policy at the United States Department of Defense.


title: Ronald Lauder

text: In 1986, Ronald Reagan named him as the United States Ambassador to Austria, a position he held until 1987. As ambassador, he fired diplomatic officer Felix Bloch, who later became known in connection with the Robert Hanssen espionage case.


title: Ronald Lauder

text: As a Republican, he made a bid to become the mayor of New York City in 1989, losing to Rudy Giuliani in the Republican primary (Giuliani lost to David Dinkins in the general election but defeated Dinkins in 1993). His campaign managers were Roger Ailes of Fox News and Arthur Finkelstein, a strong supporter of Richard Nixon. Michael Massing, writing of this nomination race, notes that politically Lauder 'seemed out of step with most American Jews; ... he ran to the right of Rudolph Giuliani. And, on Israeli issues, he was a vocal supporter of the Likud party, with long-standing ties to Benjamin Netanyahu." Lauder spent $14 million of his own funds on the race. In 1994 he successfully led a campaign to place term limits on the mayor. In the Republican primary Giuliani had 77,150 (67.0%) vote to 37,960 (33.0%) for Lauder.


title: Ronald Lauder

text: In 1998, Lauder was asked by Israeli Prime Minister Benjamin Netanyahu to begin Track II negotiations with Syrian leader Hafez al-Assad; these negotiations continued after the election of Ehud Barak to the post. Lauder communicated a new-found willingness on Assad's part to make compromises with the Israelis in an overall land for peace deal, and his draft "Treaty of Peace Between Israel and Syria" formed an important part of the (ultimately fruitless) Israeli-Syrian negotiations that occurred in January 2000 in Shepherdstown, West Virginia.


title: Ronald Lauder

text: Lauder manages investments in real estate and media, including Central European Media Enterprises and Israeli TV. In 2010, Lauder founded RWL Water, LLC.


title: Ronald Lauder

text: Lauder has been involved with organizations, such as the Conference of Presidents of Major American Jewish Organizations, the Jewish National Fund, the World Jewish Congress, the American Jewish Joint Distribution Committee, the Anti-Defamation League, the Jewish Theological Seminary, Rabbinical College of America, Brandeis University, and the Abraham Fund. With his brother he founded the Lauder Institute at Wharton School. Lauder has also served as a finance chairman of the New York Republican State Committee.


title: Ronald Lauder

text: Lauder led a movement to introduce term limits in the New York City Council, which were subsequently imposed on most NYC elected officials, including the Mayor and City Council, after a citywide referendum in 1993. In 1996, voters turned down a council proposal to extend term limits. Lauder spent $4 million on the two referendums. He has been involved in environmental conservation efforts in eastern Long Island and has served on the board of directors of the conservation organization Group for the East End since 2002.


title: Ronald Lauder

text: On November 16, 2001, Lauder opened the Neue Galerie in New York, an art museum across the street from and four blocks north of the Metropolitan Museum of Art. The Neue Galerie is dedicated to art from Germany and Austria from the early 20th century. It holds one of the best collections of works by Egon Schiele in the world.


title: Ronald Lauder

text: On June 18, 2006, he purchased from Maria Altmann and her family, the painting "Portrait of Adele Bloch-Bauer I" by Gustav Klimt for $135 million, the highest price ever paid for a painting at that time. Lauder called the painting "Our Mona Lisa". He reportedly saw Klimt's portrait as a youth in Vienna and had admired it since. The painting, a Nazi-looted art piece which had just been restored to Altmann following years of negotiation and litigation with the Austrian government, now forms the centerpiece of the museum's collection.


title: Ronald Lauder

text: Lauder has been criticized for failure to resolve a case involving the Museum of Modern Art (MoMA), which in 1997 exhibited some paintings owned by Rudolph Leopold, a Viennese doctor and art collector. An investigative article in "The New York Times" on December 24, 1997 – "A Singular Passion for Amassing Art, One Way or Another" – outlined a case involving "Portrait of Wally" by Egon Schiele, which was in the MoMA exhibition but was obtained by Leopold soon after the Nazi era. The New York County District Attorney (Manhattan) stepped in to help restore the piece to descendants of its original owner, but ownership of the painting is still in contention, nearly ten years later. Lauder has been accused of a failure to act on the case, despite being MoMA chairman at the time.


title: Ronald Lauder

text: Lauder is an honorary trustee of the World Monuments Fund, a New York-based non-profit with the mission of protecting endangered cultural heritage sites around the world.


title: Ronald Lauder

text: In 1987, Lauder established the Ronald S. Lauder Foundation, a philanthropic organization that is dedicated to rebuilding Jewish life in Central and Eastern Europe. The foundation also supports student exchange programs between New York and various capitals in Central and Eastern Europe.


title: Ronald Lauder

text: In 1998, Lauder co-founded the Alzheimer's Drug Discovery Foundation with his brother, Leonard A. Lauder. Its mission it to "rapidly accelerate the discovery of drugs to prevent, treat and cure Alzheimer's disease." Ronald continues as the Foundation's co-chairman.


title: Ronald Lauder

text: In 2020, Lauder gave 91 pieces of arms and armor to the Metropolitan Museum of Art. The 91-object gift is the museum's most significant since 1942. To honor the gift, the museum's entire group of Arms and Armor galleries is now named for Lauder.


title: Ronald Lauder

text: Lauder was elected president of the World Jewish Congress on June 10, 2007, following the resignation of Edgar Bronfman, Sr. He beat the South African businessman Mendel Kaplan and Einat Wilf of Israel by a clear margin.


title: Ronald Lauder

text: President George W. Bush appointed him to serve on the honorary delegation to accompany him to Jerusalem for the celebration of the 60th anniversary of the State of Israel in May 2008.


title: Ronald Lauder

text: In July 2009, Bernie Ecclestone faced calls from Lauder to resign as Formula One chief after he had praised Adolf Hitler in a newspaper interview and said that Hitler "got things done". Lauder said someone with Ecclestone's views should not be allowed to run such an important and popular racing series. He urged Formula One teams, drivers and host countries to suspend their cooperation with him. In reaction, Ecclestone told the news agency Associated Press that "I think the people who are saying that haven't got the power to say these things." Asked if the World Jewish Congress was influential, Ecclestone said: "It's a pity they didn't sort the banks out" and "They have a lot of influence everywhere". After a public outcry, Ecclestone apologized for his remarks and said he had "been an idiot".


title: Ronald Lauder

text: In December 2009, Lauder protested against the Roman Curia's decree recognizing the heroic virtues of Pope Pius XII, asserting that an eventual beatification would be inopportune until the Holy See's historical archives from the 1939–1945 period were opened.


title: Ronald Lauder

text: In 2011, writing in the German newspaper "Die Welt", Lauder called for Israel to be admitted into the Western defense alliance NATO: "Israel needs real guarantees for its security. European NATO member states – including Turkey – must admit the state of Israel into the Western alliance," the WJC president wrote. He referred to the uprisings in Egypt and Tunisia and said they were reminders of how "unpredictable" developments in the Middle East were. Israeli NATO membership "would send a strong signal to other countries not to take on Israel", Lauder argued.


title: Ronald Lauder

text: Lauder has also been outspoken on anti-Semitism. In an opinion article entitled "Sweden's Shame", he attacked the Swedish government, church officials and media for "fanning the flames" of hatred against Jews.


title: Ronald Lauder

text: In May 2012, Lauder condemned as "despicable" remarks made by the Norwegian sociologist Johan Galtung who had "revived anti-Semitic canards such as Jewish control of the media" and suggested that Israel's Mossad could have been behind the 2011 "massacres in Norway committed by Anders Breivik" in which 77 people died. Lauder declared: "There is a growing tendency to blame the Jews for all evil that happens under the sun. It is a scandal that a leading academic such as Galtung does not shy away from citing notorious forgeries such as the Protocols of the Elders of Zion to support his bigoted arguments."


title: Ronald Lauder

text: In August 2012, Lauder criticized Austrian politicians for failing to publicly denounce the leader of the third-largest political party in the country, the FPÖ, Heinz-Christian Strache, who had posted an anti-Semitic cartoon on his Facebook page. "Clearly, and not for the first time, the FPÖ leader is trying to whip up anti-Semitic sentiment. His repeated denials are not credible because his words and actions speak for themselves," Ronald Lauder said in a statement, adding: "This scandal shows that anti-Jewish resentment is still widespread, and unscrupulous politicians are allowed to exploit it for electioneering purposes. That is mind-boggling, and it could have negative repercussions for Austrian Jews." The Israelitische Kultusgemeinde Wien (Vienna Israelite Community) banned Lauder for allegedly interfering in its board elections. IKG President Oskar Deutsch alleged that Lauder had offered incentives to members of the IKG to support another candidate. A Lauder spokesman denied the allegations. In January 2013, it was reported that Deutsch and Lauder had resolved their dispute.


title: Ronald Lauder

text: Lauder has been strongly critical of business deals by European energy firms with Iran and called for stronger UN sanctions because of Tehran's threat against Israel and its nuclear program. In April 2008, he criticized a visit by Swiss Foreign Minister Micheline Calmy-Rey to Tehran where she met with Iran's President Mahmoud Ahmadinejad to help a Swiss company secure a multibillion-dollar contract to buy natural gas from Iran. Lauder told a press conference in Bern: "Maybe that money that Switzerland is paying to Iran will some day be used to either buy weapons to kill Israelis, or buy weapons to kill Americans, or buy missiles to be able to deliver nuclear weapons." Lauder also led diplomatic efforts to persuade European businesses to withdraw from Iran. In January 2010, he warmly welcomed the announcement by Siemens CEO Peter Löscher that his company would not seek new business in Iran.


title: Ronald Lauder

text: In February 2018, the Polish Prime Minister Mateusz Morawiecki stated that "there were Jewish perpetrators" of the Holocaust, "not only German perpetrators." Lauder condemned Morawiecki's comment as anti-Semitic, saying: "The Polish prime minister [Morawiecki] has displayed appalling ignorance with his unconscionable claim that so-called 'Jewish perpetrators' were partly responsible for the Nazi German attempt to wipe out European Jewry ... this government is going to extreme and unfathomable lengths to exonerate some of their countrymen's own complicity in the murders of their neighbors. This is nothing short of an attempt to falsify history, that is one of the very worst forms of anti-Semitism and Holocaust obfuscation. We demand an immediate retraction and apology from the Polish government of these absurd and offensive remarks.".


title: Ronald Lauder

text: in 2019, Lauder launched the Antisemitism Accountability Project (ASAP) to fund campaigns fighting federal, state, and local candidates who support or promote antisemitism.


title: Ronald Lauder

text: Lauder had donated $1.1 million in 2016 to Secure America Now (SAN). In the same year, SAN broadcast anti-Muslim social media videos in swing states just before the U.S. elections. Lauder disavowed the videos; a spokesman said that he had donated to the group "support their work in opposition to the Iran nuclear deal" (which had concluded in 2015) and "had nothing to do with any of the group's other activities"; the spokesman said that Lauder supported "interfaith respect and dialogue" and "would never be involved with insulting people of faith." The videos at issue may have been targeted at increasing turnout among supporters of Donald Trump.


title: Ronald Lauder

text: Lauder is a longtime Republican Party donor. Since 2016, Lauder has donated more than $1.6 million to pro-Donald Trump organizations. In 2020, Lauder donated $1.7 million to a new independent expenditure group that opposed criminal justice reform in New York.


title: Ronald Lauder

text: Lauder pitched the idea to Trump to buy Greenland in 2019 from Denmark. In the proposal he proposed to be the immediary in the transaction which Denmark rejected. His involvement was first reported in a 2022 a book "The Divider" by Peter Baker and his wife Susan Glasser.


title: Ronald Lauder

text: His brother supported Kathy Hochul's successful campaign for New York governor in 2022, but Ronald himself gave $11 million to the Republican challenger Lee Zeldin.


title: Ronald Lauder

text: Lauder has repeatedly come to the defense of Israel in public and is seen as an ally of Prime Minister Benjamin Netanyahu. In May 2012, he reacted "with dismay" at a suggestion by Ireland's Deputy Prime Minister and Foreign Minister Eamon Gilmore to impose a European Union-wide import ban on products made in Israeli settlements in the West Bank, which Gilmore said were "illegal" and made peace between Israel and the Palestinians "impossible". Lauder said: "Such boycott calls are cynical and hypocritical. Minister Gilmore is taking aim at the only liberal democracy in the Middle East while keeping quiet about those who really wreak havoc in the region: the Assads, Ahmadinejads and their allies Hezbollah and Hamas." He added that "the West Bank territories are legally disputed and not illegally occupied."


title: Ronald Lauder

text: In remarks to the International Council of Jewish Parliamentarians made on June 28, 2011, Lauder reportedly scolded Israeli Prime Minister Benjamin Netanyahu for a number of missteps, including lacking a diplomatic plan heading into the September UN vote on Palestinian statehood and setting preconditions for negotiations as part of the Israeli–Palestinian peace process, according to "Haaretz". However, in June 2012, on the third anniversary of Israeli Prime Minister , Lauder published a full-page advertisement in "The Wall Street Journal" and other newspapers in which he called on Palestinian President Mahmoud Abbas to return to the negotiating table. "Accept the offer to talk, President Abbas. It takes two sides to make peace," Lauder wrote.


title: Ronald Lauder

text: Lauder has participated in a number of large media deals in Israel, among which was his purchase of part of commercial television Channel 10.


title: Ronald Lauder

text: In September 2011, Israeli media published accounts that Lauder had put heavy pressure on the executives of the channel to broadcast a personal apology to the businessman Sheldon Adelson with regard to a profile that the channel had broadcast in January 2011. The apology read, "After the broadcast of the piece, we checked the accusations. Our checks revealed that the accusations were – and are – completely false ... We are very regretful that we did not check these accusations before broadcasting them." Lauder's forcing of the form of the apology led to the resignation of the channel's news chief Reudor Benziman, its news editor Ruti Yuval, and its presenter Guy Zohar (who continues in another post in Channel 10), who criticized Lauder for the pressure he exerted. Because of the attacks, detailed above, on Lauder (who had been until then the last major funder of the channel), he decided to reconsider his financial support. If the channel lost his funding, it would have difficulty continuing to operate to its current standard past October 2011.


title: Ronald Lauder

text: On November 3, 2011, The Second Authority for Television and Radio reached a decision on the issue in which it decided that the apology to Adelson broadcast by the channel was appropriate and that "no evidence has been presented that there was any intervention by the shareholders of Channel 10 on new content, or even on the text of the apology, which was agreed between the news company and the person injured by the broadcast".


title: Ronald Lauder

text: Lauder's daughter Jane is married to Kevin Warsh, a former member of the Federal Reserve Board of Governors.


title: Ronald Lauder

text: A 2007 profile of Lauder in "The New Yorker" magazine detailed his residences, including three properties in Manhattan – a townhouse on East 70th Street, the Rockefeller Guest House on East 52nd Street, as well as an apartment at 740 Park Avenue. The profile additionally listed homes in Florida, London, Paris, and Wainscott, Long Island.


title: Promoter (genetics)

text: In genetics, a promoter is a sequence of DNA to which proteins bind to initiate transcription of a single RNA transcript from the DNA downstream of the promoter. The RNA transcript may encode a protein (mRNA), or can have a function in and of itself, such as tRNA or rRNA. Promoters are located near the transcription start sites of genes, upstream on the DNA (towards the 5' region of the sense strand).


title: Promoter (genetics)

text: Promoters can be about 100–1000 base pairs long, the sequence of which is highly dependent on the gene and product of transcription, type or class of RNA polymerase recruited to the site, and species of organism.


title: Promoter (genetics)

text: Promoters control gene expression in bacteria and eukaryotes. RNA polymerase must attach to DNA near a gene for transcription to occur. Promoter DNA sequences provide an enzyme binding site. The -10 sequence is TATAAT. -35 sequences are conserved on average, but not in most promoters.


title: Promoter (genetics)

text: Artificial promoters with conserved -10 and -35 elements transcribe more slowly. All DNAs have "Closely spaced promoters" Divergent, tandem, and convergent orientations are possible. Two closely spaced promoters will likely interfere. Regulatory elements can be several kilobases away from the transcriptional start site in gene promoters (enhancers).


title: Promoter (genetics)

text: In eukaryotes, the transcriptional complex can bend DNA, allowing regulatory sequences to be placed far from the transcription site. The distal promoter is upstream of the gene and may contain additional regulatory elements with a weaker influence. RNA polymerase II (RNAP II) bound to the transcription start site promoter can start mRNA synthesis.


title: Promoter (genetics)

text: CpG islands, a TATA box, and TFIIB recognition elements can be found in promoter DNA. Weingarten-Gabbay et al. found these elements have small effects on gene expression. Figure 1 shows an enhancer looping around a gene's promoter. A connector protein dimer (e.g. CTCF or YY1) stabilizes the loop by anchoring one member on the enhancer and the other on the promoter. 47% of bidirectionally paired genes in the Gene Ontology database shared a functional category.


title: Promoter (genetics)

text: Hypermethylation downregulates both genes, while demethylation upregulates them. Non-coding RNAs are linked to mRNA promoter regions, according to research. Subgenomic promoters range from 24 to 100 nucleotides (Beet necrotic yellow vein virus). Gene expression depends on promoter binding. Unwanted gene changes can increase a cell's cancer risk.


title: Promoter (genetics)

text: MicroRNA promoters often contain CpG islands. DNA methylation forms 5-methylcytosines at the 5' pyrimidine ring of CpG cytosine residues. Some cancer genes are silenced by mutation, but most are silenced by DNA methylation. Others are regulated promoters. Selection may favor less energetic transcriptional binding.


title: Promoter (genetics)

text: Variations in promoters or transcription factors cause some diseases. Misunderstandings can result from using canonical sequence to describe a promoter.


title: Promoter (genetics)

text: For transcription to take place, the enzyme that synthesizes RNA, known as RNA polymerase, must attach to the DNA near a gene. Promoters contain specific DNA sequences such as response elements that provide a secure initial binding site for RNA polymerase and for proteins called transcription factors that recruit RNA polymerase. These transcription factors have specific activator or repressor sequences of corresponding nucleotides that attach to specific promoters and regulate gene expression.


title: Promoter (genetics)

text: Promoters represent critical elements that can work in concert with other regulatory regions (enhancers, silencers, boundary elements/insulators) to direct the level of transcription of a given gene.


title: Promoter (genetics)

text: A promoter is induced in response to changes in abundance or conformation of regulatory proteins in a cell, which enable activating transcription factors to recruit RNA polymerase.


title: Promoter (genetics)

text: As promoters are typically immediately adjacent to the gene in question, positions in the promoter are designated relative to the transcriptional start site, where transcription of DNA begins for a particular gene (i.e., positions upstream are negative numbers counting back from -1, for example -100 is a position 100 base pairs upstream).


title: Promoter (genetics)

text: In the cell nucleus, it seems that promoters are distributed preferentially at the edge of the chromosomal territories, likely for the co-expression of genes on different chromosomes. Furthermore, in humans, promoters show certain structural features characteristic for each chromosome.


title: Promoter (genetics)

text: In bacteria, the promoter contains two short sequence elements approximately 10 (Pribnow Box) and 35 nucleotides "upstream" from the transcription start site.


title: Promoter (genetics)

text: The above promoter sequences are recognized only by RNA polymerase holoenzyme containing sigma-70. RNA polymerase holoenzymes containing other sigma factors recognize different core promoter sequences.


title: Promoter (genetics)

text: Promoters can be very closely located in the DNA. Such “closely spaced promoters” have been observed in the DNAs of all life forms, from Humans to prokaryotes and are highly conserved. Therefore, they may provide some (presently unknown) advantages.


title: Promoter (genetics)

text: These pairs of promoters can be positioned in divergent, tandem, and convergent directions. They can also be regulated by transcription factors and differ in various features, such as the nucleotide distance between them, the two promoter strengths, etc.


title: Promoter (genetics)

text: The most important aspect of two closely spaced promoters is that they will, most likely, interfere with each other. Several studies have explored this using both analytical and stochastic models. There are also studies that measured gene expression in synthetic genes or from one to a few genes controlled by bidirectional promoters.


title: Promoter (genetics)

text: More recently, one study measured most genes controlled by tandem promoters in "E. coli". In that study, it was measured and then modeled two main forms of interference. One is when an RNAP is on the downstream promoter, blocking the movement of RNAPs elongating from the upstream promoter. The other is when the two promoters are so close that when an RNAP sits on one of the promoters, it blocks any other RNAP from reaching the other promoter. These events are possible because the RNAP occupies several nucleotides when bound to the DNA, including in transcription start sites.


title: Promoter (genetics)

text: Similar events occur when the promoters are in divergent and convergent formations. The possible events also depend on the distance between them.


title: Promoter (genetics)

text: Eukaryotic promoters are diverse and can be difficult to characterize, however, recent studies show that they are divided in more than 10 classes.


title: Promoter (genetics)

text: Gene promoters are typically located upstream of the gene and can have regulatory elements several kilobases away from the transcriptional start site (enhancers). In eukaryotes, the transcriptional complex can cause the DNA to bend back on itself, which allows for placement of regulatory sequences far from the actual site of transcription. Eukaryotic RNA-polymerase-II-dependent promoters can contain a TATA box (consensus sequence TATAAA), which is recognized by the general transcription factor TATA-binding protein (TBP); and a B recognition element (BRE), which is recognized by the general transcription factor TFIIB. The TATA element and BRE typically are located close to the transcriptional start site (typically within 30 to 40 base pairs).


title: Promoter (genetics)

text: Eukaryotic promoter regulatory sequences typically bind proteins called transcription factors that are involved in the formation of the transcriptional complex. An example is the E-box (sequence CACGTG), which binds transcription factors in the basic helix-loop-helix (bHLH) family (e.g. BMAL1-Clock, cMyc). Some promoters that are targeted by multiple transcription factors might achieve a hyperactive state, leading to increased transcriptional activity.


title: Promoter (genetics)

text: Up-regulated expression of genes in mammals is initiated when signals are transmitted to the promoters associated with the genes. Promoter DNA sequences may include different elements such as CpG islands (present in about 70% of promoters), a TATA box (present in about 24% of promoters), initiator (Inr) (present in about 49% of promoters), upstream and downstream TFIIB recognition elements (BREu and BREd) (present in about 22% of promoters), and downstream core promoter element (DPE) (present in about 12% of promoters). The presence of multiple methylated CpG sites in CpG islands of promoters causes stable silencing of genes. However, experiments by Weingarten-Gabbay et al. showed that the presence or absence of the other elements have relatively small effects on gene expression. Two sequences, the TATA box and Inr, caused small but significant increases in expression (45% and 28% increases, respectively). The BREu and the BREd elements significantly decreased expression by 35% and 20%, respectively, and the DPE element had no detected effect on expression.


title: Promoter (genetics)

text: Cis-regulatory modules that are localized in DNA regions distant from the promoters of genes can have very large effects on gene expression, with some genes undergoing up to 100-fold increased expression due to such a cis-regulatory module. These cis-regulatory modules include enhancers, silencers, insulators and tethering elements. Among this constellation of elements, enhancers and their associated transcription factors have a leading role in the regulation of gene expression.


title: Promoter (genetics)

text: Enhancers are regions of the genome that are major gene-regulatory elements. Enhancers control cell-type-specific gene expression programs, most often by looping through long distances to come in physical proximity with the promoters of their target genes. In a study of brain cortical neurons, 24,937 loops were found, bringing enhancers to promoters. Multiple enhancers, each often at tens or hundred of thousands of nucleotides distant from their target genes, loop to their target gene promoters and coordinate with each other to control expression of their common target gene.


title: Promoter (genetics)

text: The schematic illustration in this section shows an enhancer looping around to come into close physical proximity with the promoter of a target gene. The loop is stabilized by a dimer of a connector protein (e.g. dimer of CTCF or YY1), with one member of the dimer anchored to its binding motif on the enhancer and the other member anchored to its binding motif on the promoter (represented by the red zigzags in the illustration). Several cell function specific transcription factors (there are about 1,600 transcription factors in a human cell) generally bind to specific motifs on an enhancer and a small combination of these enhancer-bound transcription factors, when brought close to a promoter by a DNA loop, govern the level of transcription of the target gene. Mediator (coactivator) (a complex usually consisting of about 26 proteins in an interacting structure) communicates regulatory signals from enhancer DNA-bound transcription factors directly to the RNA polymerase II (pol II) enzyme bound to the promoter.


title: Promoter (genetics)

text: Enhancers, when active, are generally transcribed from both strands of DNA with RNA polymerases acting in two different directions, producing two eRNAs as illustrated in the Figure. An inactive enhancer may be bound by an inactive transcription factor. Phosphorylation of the transcription factor may activate it and that activated transcription factor may then activate the enhancer to which it is bound (see small red star representing phosphorylation of transcription factor bound to enhancer in the illustration). An activated enhancer begins transcription of its RNA before activating a promoter to initiate transcription of messenger RNA from its target gene.


title: Promoter (genetics)

text: Bidirectional promoters are short (<1 kbp) intergenic regions of DNA between the 5' ends of the genes in a bidirectional gene pair. A “bidirectional gene pair” refers to two adjacent genes coded on opposite strands, with their 5' ends oriented toward one another. The two genes are often functionally related, and modification of their shared promoter region allows them to be co-regulated and thus co-expressed. Bidirectional promoters are a common feature of mammalian genomes. About 11% of human genes are bidirectionally paired.


title: Promoter (genetics)

text: Bidirectionally paired genes in the Gene Ontology database shared at least one database-assigned functional category with their partners 47% of the time. Microarray analysis has shown bidirectionally paired genes to be co-expressed to a higher degree than random genes or neighboring unidirectional genes. Although co-expression does not necessarily indicate co-regulation, methylation of bidirectional promoter regions has been shown to downregulate both genes, and demethylation to upregulate both genes. There are exceptions to this, however. In some cases (about 11%), only one gene of a bidirectional pair is expressed. In these cases, the promoter is implicated in suppression of the non-expressed gene. The mechanism behind this could be competition for the same polymerases, or chromatin modification. Divergent transcription could shift nucleosomes to upregulate transcription of one gene, or remove bound transcription factors to downregulate transcription of one gene.


title: Promoter (genetics)

text: Some functional classes of genes are more likely to be bidirectionally paired than others. Genes implicated in DNA repair are five times more likely to be regulated by bidirectional promoters than by unidirectional promoters. Chaperone proteins are three times more likely, and mitochondrial genes are more than twice as likely. Many basic housekeeping and cellular metabolic genes are regulated by bidirectional promoters.


title: Promoter (genetics)

text: The overrepresentation of bidirectionally paired DNA repair genes associates these promoters with cancer. Forty-five percent of human somatic oncogenes seem to be regulated by bidirectional promoters – significantly more than non-cancer causing genes. Hypermethylation of the promoters between gene pairs WNT9A/CD558500, CTDSPL/BC040563, and KCNK15/BF195580 has been associated with tumors.


title: Promoter (genetics)

text: Certain sequence characteristics have been observed in bidirectional promoters, including a lack of TATA boxes, an abundance of CpG islands, and a symmetry around the midpoint of dominant Cs and As on one side and Gs and Ts on the other. A motif with the consensus sequence of TCTCGCGAGA, also called the CGCG element, was recently shown to drive PolII-driven bidirectional transcription in CpG islands. CCAAT boxes are common, as they are in many promoters that lack TATA boxes. In addition, the motifs NRF-1, GABPA, YY1, and ACTACAnnTCCC are represented in bidirectional promoters at significantly higher rates than in unidirectional promoters. The absence of TATA boxes in bidirectional promoters suggests that TATA boxes play a role in determining the directionality of promoters, but counterexamples of bidirectional promoters do possess TATA boxes and unidirectional promoters without them indicates that they cannot be the only factor.


title: Promoter (genetics)

text: Although the term "bidirectional promoter" refers specifically to promoter regions of mRNA-encoding genes, luciferase assays have shown that over half of human genes do not have a strong directional bias. Research suggests that non-coding RNAs are frequently associated with the promoter regions of mRNA-encoding genes. It has been hypothesized that the recruitment and initiation of RNA polymerase II usually begins bidirectionally, but divergent transcription is halted at a checkpoint later during elongation. Possible mechanisms behind this regulation include sequences in the promoter region, chromatin modification, and the spatial orientation of the DNA.


title: Promoter (genetics)

text: A subgenomic promoter is a promoter added to a virus for a specific heterologous gene, resulting in the formation of mRNA for that gene alone. Many positive-sense RNA viruses produce these subgenomic mRNAs (sgRNA) as one of the common infection techniques used by these viruses and generally transcribe late viral genes. Subgenomic promoters range from 24 nucleotide (Sindbis virus) to over 100 nucleotides (Beet necrotic yellow vein virus) and are usually found upstream of the transcription start.


title: Promoter (genetics)

text: A wide variety of algorithms have been developed to facilitate detection of promoters in genomic sequence, and promoter prediction is a common element of many gene prediction methods. A promoter region is located before the -35 and -10 Consensus sequences. The closer the promoter region is to the consensus sequences the more often transcription of that gene will take place. There is not a set pattern for promoter regions as there are for consensus sequences.


title: Promoter (genetics)

text: Changes in promoter sequences are critical in evolution as indicated by the relatively stable number of genes in many lineages. For instance, most vertebrates have roughly the same number of protein-coding genes (about 20,000) which are often highly conserved in sequence, hence much of evolutionary change must come from changes in gene expression.


title: Promoter (genetics)

text: Given the short sequences of most promoter elements, promoters can rapidly evolve from random sequences. For instance, in "E. coli", ~60% of random sequences can evolve expression levels comparable to the wild-type lac promoter with only one mutation, and that ~10% of random sequences can serve as active promoters even without evolution.